PMID- 9260113
TI  - Ultrastructural features of the bone response to a plasma-sprayed hydroxyapatite
      coating in sheep.
AB  - The intentions of this study were to characterize the macroscopic, microscopic,
      and structural aspects of a plasma-sprayed implant and to thoroughly investigate
      bone tissue response after its implantation in sheep. Therefore, we used scanning
      electron microscopy, transmission electron microscopy (TEM), high-resolution TEM,
      X-ray diffraction, and energy-dispersive X-ray analyses. Assessment of the
      biomaterial prior to implantation showed a coating with irregular outlines and
      varying thickness, mainly consisting of hydroxyapatite (HA) covering a rough
      metallic implant core. Six months after insertion of the HA-coated Ti-6A1-4V
      implant, neither mechanical failure of the coating-substrate interface nor a
      significant loss of coating thickness was evident. However, an occasional lack of
      HA coating and phagocytosis of HA particles were noted. More generally, the
      implant was surrounded by well-mineralized bone investing the smallest cavities
      of the plasma-sprayed layer. Newly formed microcrystals with size, shape, and
      structure similar to those of bone apatite crystals were growing directly at the
      coating surface. These results suggest that the bone-bonding behavior of the
      considered grooved implant should provide satisfactory osseointegration and be
      suitable for fixed prostheses.

PMID- 9260114
TI  - Cardiovascular responses to neuromuscular blockade in the anemic ovine fetus.
AB  - Currently little is known about the cardiovascular responses of the anemic fetus
      to neuromuscular blockade. We hypothesized that, despite marked anemia with
      potentially decreased cardiac reserve, the fetal responses to Pancuronium
      neuromuscular blockade would differ significantly when compared with
      neuromuscular blockade with Atracurium (a cardiovascular sparing agent). Ten
      fetal sheep (137 +/- 1 (SE) days gestation) were divided into three groups (21
      experiments): Pancuronium (n = 7), Atracurium (n = 6), and Control (n = 8). Fetal
      anemia (Hct = 21.8 +/- 0.7%) was produced by serial hemorrhage over 3 days. Fetal
      arterial (FAP) and venous (FVP) pressures, heart rate (FHR), and arterial pH,
      pO2, and pCO2 were measured at -20, 0, 10, 20, 30, 60, and 90 minutes relative to
      neuromuscular blockade. Data were analyzed by three-way ANOVA for repeated
      measures. Pancuronium neuromuscular blockade increased FHR (15-20 bpm, P < .0001)
      and decreased FVP (-0.8 mm Hg, P < .0001). Atracurium had no effect on FHR, FAP,
      or FVP. Fetal pH (0.024, P < .0001) and pO2 (1-2 mm Hg, P = .0001) increased in
      both neuromuscular-blocked groups. Fetal pCO2 decreased in the Pancuronium
      blocked animals (P = .02). We conclude that, in anemic fetuses, neuromuscular
      blockade with Atracurium produced minimal cardiovascular effects when compared to
      neuromuscular blockade with Pancuronium. Both agents produced small improvements
      in fetal pH and blood gases.

PMID- 9260115
TI  - Effects of narcotic and non-narcotic continuous epidural anesthesia on
      intrapartum fetal heart rate tracings as measured by computer analysis.
AB  - OBJECTIVE: To evaluate the effect of narcotic and non-narcotic continuous
      epidural anesthesia on intrapartum fetal heart rate (FHR) tracings as measured by
      computer analysis. METHODS: We studied 37 women with uncomplicated pregnancies at
      term with reactive FHR tracings. The women were randomized to receive epidural
      anesthesia with either bupivicaine with fentanyl or bupivicaine alone. One-hour
      FHR tracings were obtained before epidural anesthesia. Thirty minutes after the
      initial bolus of the epidural a repeat computer analysis of 60-minute FHR tracing
      was obtained. Median values are reported for FHR parameters with statistical
      analysis performed by the Mann-Whitney U and Wilcoxon signed rank tests where
      appropriate. A power calculation was performed using a power of 90% to determine
      a required sample size of 28 patients. Statistical significance was set at P <
      .05. RESULTS: In early first stage of labor, there was no significant difference
      in pre- and postepidural anesthesia FHR baseline, accelerations of 10 and 15
      beats per minute, episodes of high and low variation, and short- and long-term
      variation when using either narcotic or non-narcotic anesthetic agents.
      CONCLUSIONS: Thus, the clinician can consider the use of narcotic as well as non
      narcotic continuous epidural anesthesia in the dosages used in our study with its
      attendant advantages without fear of obscuring the fetal heart rate tracing.

PMID- 9260116
TI  - Increase of fetal hematocrit decreases the middle cerebral artery peak systolic
      velocity in pregnancies complicated by rhesus alloimmunization.
AB  - Our hypothesis for this study was that an increase in fetal hematocrit would
      decrease the middle cerebral artery peak systolic velocity. Seventeen pregnancies
      complicated by Rh alloimmunization were included in this study. Middle cerebral
      artery peak systolic velocity was studied by Doppler ultrasound before and after
      intrauterine transfusion with adult packed red blood cells (hematocrit = 80-85%).
      Mean gestational age at time of study was 27 weeks. Paired t-test was used for
      statistical comparison. A P value of < 0.05 was considered statistically
      significant. The fetal hematocrit ranged from 5.9% to 30% prior to the procedure,
      and it was 24.8-53.4%, following the procedure. Mean middle cerebral artery peak
      systolic velocity was 46.2 +/- 10.7 cm/s prior to the procedure, and it decreased
      to 31.7 +/- 9.5 cm/s following the procedure (P < 0.01). The increase of fetal
      hematocrit significantly decreases the middle cerebral artery peak systolic
      velocity supporting data that this Doppler measurement may be useful for the
      diagnosis of fetal anemia.

PMID- 9260117
TI  - Use of ultrasound longitudinal data in the diagnosis of abnormal fetal growth.
AB  - Normal ranges for biparietal diameter (BPD), head circumference (HC), abdominal
      circumference (AC), and femur length (FL) were established from longitudinal data
      of singleton pregnancies of Arabian mothers. The data were used to develop a
      normogram of fetal "growth rate" for each parameter. It is suggested that a
      normogram of "fetal growth" is of less variance than absolute measurements and
      could be more useful in the early identification of growth abnormalities than
      absolute fetal measurements.

PMID- 9260118
TI  - Total parenteral nutrition in pregnancy: case review and guidelines for
      calculating requirements.
AB  - Although many aspects of the use of total parenteral nutrition (TPN) in pregnancy
      are controversial, the long-term sequelae of maternal malnutrition in fetal
      health are not. To avoid these complications, TPN is advocated for use in
      pregnancies complicated by maternal starvation. The purpose of this paper is to
      outline an easy to follow method for prescribing TPN solution to meet the needs
      of the gravid patients.

PMID- 9260119
TI  - Spontaneous spinal extradural hematoma during pregnancy.
AB  - BACKGROUND: Spontaneous spinal hematomas are rare in pregnancy, and only two
      cases have previously been described. This report reviews other similar cases and
      discusses the aetiology and management of this condition in relation to
      pregnancy. CASE: A 26-year-old primigravida presented at 35 weeks of gestation
      with a history of sudden onset of back pain and weakness with loss of sensation
      of her legs. On examination there was tenderness over the seventh thoracic
      vertebra with loss of sensation below the level of the T7 dermatome and reduced
      power in both lower limbs. Magnetic resonance imaging demonstrated an anterior
      extradural lesion in the mid-thoracic region of the spinal cord. An elective
      cesarean section was performed followed by a costotransversectomy and removal of
      an extradural hematoma. The patient's neurological function subsequently
      improved. CONCLUSION: Acute spontaneous spinal extradural hematoma occurring
      during pregnancy can be associated with successful outcome following prompt
      diagnosis and surgical treatment.

PMID- 9260120
TI  - Shoulder dystocia and operative vaginal delivery.
AB  - Our objective was to determine the factors involved in the development of
      shoulder dystocia in association with operative vaginal delivery. In this
      prospective study, patients who were candidates for operative vaginal delivery
      were randomized either to forceps (N = 315) or vacuum with M-cup (N = 322) and
      timed from initial placement of instrument to final delivery. Data were gathered
      prior to and after instrumental delivery. Statistics used were Pearson chi
      square, Fisher's exact, analysis of variance, and multiple logistic regression.
      There were a total of 21 patients with shoulder dystocia in both groups (3.3%
      incidence). Discriminant factors that did nor meet significance included use of
      epidural analgesia (P = .12), station (P = .99), previous vaginal delivery (P =
      .99), fetal gender (P = .54), indication for operative vaginal delivery (P =
      .63), > 45 degrees rotation (P = .68), use of episiotomy (P = .62), maternal
      weight (P = .26), and maternal diabetes (P = .08). Nearly attaining significance
      in univariate analysis was randomization to vacuum (P = .052). Significant
      factors included gestational age (P = .03), time required to effect delivery (P =
      .007), and birthweight (P = .0001). When these factors were subjected to stepwise
      multiple logistic regression, three factors remained as significant associations
      with shoulder dystocia: randomization to vacuum (P = .04), time for delivery (P =
      .03), and birthweight (P = .0001). In this operative vaginal delivery trial,
      shoulder dystocia was strongly associated with large fetal size, longer time to
      delivery, and the use of vacuum for delivery.

PMID- 9260121
TI  - Rising incidence of gastroschisis in teenage pregnancies.
AB  - A population-based incidence of gastroschisis using the unique characteristics of
      a geographically isolated state with a single tertiary obstetric and pediatric
      hospital has been developed via retrospective data review. Sixty-four cases of
      gastroschisis were identified during the period 1980 to 1993. With 332,530
      deliveries in the 14-year review period, the population incidence of
      gastroschisis is 1.80 per 10,000 births (95% CI 1.40-2.32). There has been a rise
      in incidence from 0.48 per 10,000 births in 1980 to 3.16 per 10,000 births in
      1993 (NS). This alteration in incidence is an age-group specific event. The age
      group 15-19 years, which accounts for a consistent 6.5% of total deliveries, has
      10 times the incidence of the age range 25-29 years. A sharp rise in the
      occurrence of gastroschisis in women 15-19 years was observed, with the incidence
      increasing from 4.0 to 26.5 per 10,000 births over the period of review.
      Increased use of prenatal ultrasound has made antenatal diagnosis usual and
      consequent referral to the tertiary referral hospital for delivery. There was a
      46% incidence of smoking, and 19% of women admitted to recreational drug use. A
      strong association with preterm delivery and low birthweight was present with a
      50% incidence of low birthweight, eight times the state incidence (OR 14.82, 95%
      CI 8.97-24.51). The rate of preterm birth was 46.1% vs. 6.6% in the general
      obstetric population (OR 12.11, 95% CI 6.45-22.73). There was a high incidence of
      perceived fetal distress, reflected in an increased rate of emergency cesarean
      section (23% vs. 8%, OR 4.31, 95% CI 1.91-9.74). The early neonatal outcome was
      satisfactory with three neonatal deaths and an overall perinatal survival rate of
      85%. The increase in incidence of gastroschisis in this population-based study
      reveals a strong association with young maternal age. Investigation into possible
      etiologic factors to explain this observation is required.

PMID- 9260122
TI  - Epidemiological pitfalls using Medicaid data in reproductive health research.
AB  - The purpose of this report is to discuss methodologic issues in using Medicaid
      claims data to conduct epidemiologic analyses in reproductive health. We
      conducted case-control studies that used Medicaid claims data to evaluate two
      specific reproductive health questions. Case and control pregnancies were
      selected from among 106,000 women identified in a Medicaid claims file. Medical
      record review was conducted for randomly selected cases and controls. Several
      methodological issues were identified. Women could contribute multiple
      pregnancies that qualified as either case pregnancies, control pregnancies, or
      both. The results of the medical record review indicated that 25% of one case
      group (low-birthweight infants) could not be confirmed, and 70% of the second
      case group (CNS birth defects) were misclassified. Thirty-five percent of women
      classified as not having undergone diagnostic ultrasonography based on Medicaid
      claims data had evidence of having received diagnostic ultrasound during
      pregnancy on the basis of medical record review. Several problems were
      encountered with the use of Medicaid billing data to address epidemiologic
      questions in reproductive health. Although solutions to some of these problems
      could be identified, others could not be addressed without careful review of the
      medical records. These limitations may not apply to all state Medicaid databases
      or other claims data, but they should be carefully considered when planning
      claims-based analyses of reproductive health issues.

PMID- 9260123
TI  - Pregnancy outcome following donor embryo replacement.
AB  - OBJECTIVE: To investigate the occurrence of adverse perinatal outcome among donor
      embryo pregnancies. STUDY DESIGN: Thirty-five pregnancies following donor embryo
      replacement were delivered between 1990 and 1994. Thirty-two pregnancies
      following standard in vitro fertilization (IVF) in women of 34 years of age or
      older were delivered during the same time period. All pregnancies meeting study
      criteria and who conceived through the same assisted reproductive technology
      program were included. Patients electing multifetal pregnancy reduction in either
      group were excluded. RESULTS: The patients were similar with regard to age and
      parity. There was no difference in the mean number of embryos transferred between
      the groups or between those conceiving singleton or multiple gestations. The
      occurrence of spontaneous abortion was 34% in the donor embryo group and 25% in
      the control IVF group. Of the continuing pregnancies, there was a trend toward
      more cesarean births in the donor embryo group, but it was not statistically
      significant. Birthweights and gestational ages also were not different between
      the groups. Preterm birth occurred in approximately one-third of the pregnancies
      in each group owing largely to the number of multiple gestations. The incidence
      of preeclampsia was 26% among donor embryo pregnancies and 29% among control
      group pregnancies. Adverse outcome defined as preterm birth with or without
      preeclampsia occurred in over one-third of the pregnancies in each group.
      CONCLUSION: There is no increase in adverse perinatal outcome among donor embryo
      pregnancies compared to age-like control IVF pregnancies. Modest increases in the
      occurrence of adverse outcome among such pregnancies cannot be excluded by the
      data in the current report.

PMID- 9260124
TI  - Isolated mild ventriculomegaly: associated karyotypic abnormalities and in utero
      observations.
AB  - OBJECTIVE: The incidence of abnormal chromosomes in fetuses with mild lateral
      ventriculomegaly as an isolated prenatal ultrasound finding is not well
      established, and the rate of progression to more severe ventriculomegaly is
      uncertain. We wished to better define both the incidence of karyotypic
      abnormalities and the in utero course of fetuses with isolated mild
      ventriculomegaly. SUBJECTS AND METHODS: From July 1992 to September 1994, all
      cases of mild ventriculomegaly at our institution were reviewed (N = 94). Forty
      six were isolated. Of these, 25 had genetic evaluation, and 37 had serial
      ultrasound examination. We evaluated the frequencies of karyotype abnormality and
      in utero progression for atrial measurements of 11-15 mm. RESULTS: In fetuses
      with atria 11-15 mm, three of the 25 karyotypes were abnormal (47 XXY and two 47
      + 21, giving an incidence of 12% (95% CI 4.2-30.1%). Of the 37 with serial scans,
      five resolved in utero, 11 remained unchanged, and 20 progressed (one beyond 15
      mm). CONCLUSION: Isolated mild ventriculomegaly is associated with a
      significantly increased incidence of chromosomal abnormalities. Therefore, these
      patients should be offered genetic testing. When mild and isolated, some fetuses
      will show in utero resolution of the ventriculomegaly. Progression to more severe
      degrees of hydrocephalus is uncommon.

PMID- 9260125
TI  - Use of surgical pass trays to reduce intraoperative glove perforations.
AB  - This randomized prospective study evaluated the surgical pass tray to reduce
      intraoperative glove perforation during cesarean delivery. Surgical team members
      were assigned to employ normal instrument pass techniques or surgical pass tray
      during all cesarean deliveries. Surgical team members were asked to record their
      surgical role and level of training. Gloves were collected and tested using
      standard hydrosufflation techniques. Additional variables studied were patient
      weight, surgical indication, estimated blood loss, and length of surgery. A total
      of 192 cesarean sections were performed during the study period, for which 165
      were studied. Data collection was considered adequate in 156 cases. Four hundred
      forty-four pairs of gloves were collected and tested, including 38 double glove
      sets. Seventy-eight perforations were noted in 444 pairs of gloves, including 11
      in the double glove sets. Among surgeries assigned to use pass trays, 221 pairs
      of gloves were obtained with 42 (19.0%) perforations noted. Surgeries assigned to
      the control group contributed 223 glove sets of which 36 (16.1%) perforations
      were noted (P = .5). There were no complete perforations noted in the total of
      double glove sets. The frequency of glove perforations is not reduced by using
      surgical pass trays. While there is no demonstrated benefit in using pass trays
      there appears to be little adverse impact.

PMID- 9260126
TI  - Replacement of a damaged fixed partial denture pontic by adding it to the
      existing removable denture: a clinical report.
AB  - In this clinical report, a procedure is described for replacement of a damaged
      FPD casting soldered to the corresponding site on an existing removable denture.
      This procedure obviates the need for fabrication of a new FPD.

PMID- 9260127
TI  - Conservative approach to posttraumatic treatment of maxillary anterior teeth: a
      clinical report.
AB  - This clinical report emphasizes that comprehensive treatment planning, whether
      simple or complex, requires interdisciplinary knowledge. Conservative treatment
      was implemented for this patient, a 29-year-old woman with a posttraumatic
      anterior open occlusal relationship, crowding, and a shifted midline. The
      treatment plan involved selective occlusal grinding, adjunctive orthodontics,
      periodontal surgery, and cosmetic dentistry and proved to be highly successful.

PMID- 9260128
TI  - Longevity of fixed partial dentures.
AB  - STATEMENT OF PROBLEM: The anticipated length of service and reasons for
      replacement of fixed partial dentures (FPDs) are a frequent inquiry by patients.
      Previous reports have provided limited information on material and techniques
      used in restoration or standards in evaluations of restorations at delivery.
      PURPOSE: This study determined the reasons for failure and length of service for
      FPDs delivered with specific clinical, radiographic, and laboratory procedures.
      METHODS: A clinical and retrospective chart review was conducted on all patients
      with FPDs who were treated in the prosthodontic clinic at the University of Iowa
      Hospital for routine dental hygiene recalls during a 6-month period. Fifty
      patients were examined with a total of 89 FPDs. Of the 89 FPDs, 13, or 15%, were
      identified as failures or had been replaced because of failure. Dental caries was
      the most frequent cause of failure (38%), followed by periapical involvements
      (15%), perforated occlusal surfaces (15%), fractured post and cores (8%),
      defective margins (8%), fractured teeth (7%), and porcelain failures (8%). The
      mean length of service for failed FPDs ranged from 16.0 years, because of failure
      from dental caries, to 4.1 years, because of a fractured post and core. RESULTS:
      A linear regression model of years in service against number of failed FPDs
      indicated that the number of years in service provided no information on
      predictability of failure for FPDs. CONCLUSIONS: This study supported previous
      reports of dental caries as the primary cause for failure of FPDs, but specific
      radiographic, clinical, and laboratory procedures can increase the length of
      service of these restorations.

PMID- 9260129
TI  - Shear bond strengths of a two-paste system resin luting agent used to bond alloys
      to enamel.
AB  - STATEMENT OF PROBLEM: Adhesive resin luting agents are used to successfully bond
      the metal surfaces of fixed prostheses to teeth. Panavia 21 luting agent is a new
      addition to the series of Panavia adhesive resin luting agents. PURPOSE: This
      investigation measured the shear bond strengths of two types of alloy specimens
      (Olympia and Rexillium III) bonded to prepared human enamel (etched and unetched)
      with Panavia 21. MATERIAL AND METHODS: After a simulated porcelain firing
      sequence, the alloy specimens were bonded to the teeth and subjected to shear
      testing after water storage for 2 weeks, thermocycling for 500 cycles, and water
      storage for an additional 2 weeks. Data were analyzed with a two-way analysis of
      variance (alpha = 0.05). RESULTS: The shear bond strengths of Rexillium III and
      tinplated Olympia specimens bonded to prepared and unetched enamel were
      significantly lower than for specimens bonded to prepared and etched enamel with
      Panavia 21 luting agent.

PMID- 9260131
TI  - Soldering and remelting influence on fatigue strength of cobalt-chromium alloys.
AB  - STATEMENT OF PROBLEM: For laboratory production, it would be economically
      advisable to reuse excess cobalt-chromium alloys in manufacturing partial denture
      frameworks. Furthermore, discrepancies in fit, modifications, repairs, and also
      economic factors could lead to soldering procedure on the metal framework.
      PURPOSE: This study evaluated the influence of soldering and remelting procedures
      on the fatigue strength of Steldent, Dentorium, and Biosil cobalt-chromium
      alloys, as new alloys and in a mixture of new and previously casted alloy and
      when submitted or not submitted to conventional soldering procedure. MATERIAL AND
      METHODS: The soldering procedure was conducted in rod specimens 1.7 mm in
      diameter made with new, or with a mixture of new and reused alloy (n = 10 per
      group). The results were compared with those of intact rods. The fatigue strength
      was carried out with a cyclic testing machine simulating the insertion and the
      removal of partial dentures. After failure, the fracture surface was examined
      with a scanning electron microscope. RESULTS: The soldered specimens revealed
      1119 loading cycles before fracture. These means differed statistically from
      those of intact alloys, which disclosed 2733 cycles before failure (p < 0.05).
      Statistical analysis indicated that the soldering procedure reduced fatigue
      strength of all new alloys or those in a mixture of new and previously casted
      alloys. It was also found that the soldering procedure may cause premature
      failure of a removable partial denture. Photomicrographs from fracture surfaces
      revealed the presence of inclusions and voids. Conversely, there were no
      significant differences between new and reused specimens, soldered or not (p >
      0.05), which suggested that it may be possible to reuse excess cobalt-chromium
      alloys without compromising the fatigue strength of the framework.

PMID- 9260130
TI  - Bond strengths of resin-to-metal bonding systems.
AB  - STATEMENT OF PROBLEM: Resinous materials for the veneers of fixed prostheses
      commonly require mechanical retention on metal substructures because there is no
      chemical adhesion. However, mechanical retention does not restrict creation of a
      marginal gap at the resin-metal interface, which can cause discoloration or
      detachment of resinous material. The development of a chemical resin-to-metal
      bonding could resolve this problem and also reduce the need for mechanical
      retention (pearls, wires) on metal frameworks. PURPOSE: This study evaluated six
      current methods with the use of various storage conditions to predict clinical
      efficacy. MATERIAL AND METHODS: Six resin-to-metal bonding systems were tested:
      Silicoater, Silicoater MD, Rocatec, OVS, Sebond, and Spectra-Link. All specimens
      were examined in bending tests after 24 hours of dry storage (category A), after
      24 hours of water storage and thermocycling (category B), and after 2 months of
      water storage and thermocycling (category C). Tensional tests were completed for
      all bonding systems after dry storage, and microscopic examination (optical and
      SEM) was performed for all specimens. RESULTS AND CONCLUSIONS: This study
      indicated that certain systems can provide stable bonding of resin to metal
      substructures despite prolonged wet storage and intensive thermocycling. These
      systems can also be used clinically without retentive configurations on metal
      frameworks, resulting in better esthetics. Some bonding systems revealed
      progressive weakening of bond strengths, so research is needed to verify their
      clinical efficacy.

PMID- 9260132
TI  - Lased and sandblasted denture base surface preparations affecting resilient liner
      bonding.
AB  - STATEMENT OF PROBLEM: Adhesive failure between the liner and the denture base
      creates an environment for potential bacterial growth and accelerated breakdown
      of the soft liner resulting in a deteriorating prosthesis. PURPOSE: This study
      evaluated the effects of a specific sandblasted or lased preparation on the
      interfacial bonding of polymethyl methacrylate and silicone and polyethyl
      methacrylate resilient liners. MATERIAL AND METHODS: Polymethyl methacrylate test
      specimens were fabricated and received one of three surface treatments: untreated
      (control), sandblasted (250 microns aluminum oxide particles), and lased (carbon
      dioxide). Polyethyl methacrylate and silicone resilient lining materials were
      applied to these surfaces and the peel strengths were determined with the
      American Society for Testing and Materials peelin-adhesion test. RESULTS:
      Altering the polymethyl methacrylate surface by sandblasting significantly
      reduced the peel strengths for the polymethyl methacrylate/polyethyl methacrylate
      and polymethyl methacrylate/silicone specimens. Altering the polymethyl
      methacrylate surface by delivering carbon dioxide laser energy to form a grid
      pattern produced lower peel strengths that were statistically significant from
      the controls for the polymethyl methacrylate/polyethyl methacrylate specimens,
      but not so for the polymethyl methacrylate/silicone specimens. Untreated
      polymethyl methacrylate/polyethyl methacrylate peel strengths were significantly
      higher than polymethyl methacrylate/silicone. CONCLUSIONS: Results of this study
      imply that mechanical surface preparation of denture bases before application of
      a resilient liner may not be warranted.

PMID- 9260133
TI  - Mandibular overdentures anchored to single implants: a five-year prospective
      study.
AB  - STATEMENT OF PROBLEM: It is unknown what minimum number of implants are required
      to satisfactorily support and retain a mandibular overdenture. PURPOSE: The
      purpose of this study was to evaluate a treatment modality by using mandibular
      overdentures anchored to single implants in a geriatric patient population.
      MATERIAL AND METHODS: Twenty-one patients with a mean age of 74.2 years were
      treated with single implants inserted at the mandibular midline according to the
      standard two-stage surgical technique. O-Ring or ball attachments were connected
      to the implants and served as overdenture anchorage. Implant success rate,
      improvement of oral comfort and function, condition of the peri-implant soft
      tissues, Periotest values, and the interproximal marginal bone level were
      evaluated for up to 5 years after delivery of the overdentures. RESULTS: None of
      the implants were lost during the follow-up period. A mean marginal bone loss of
      1.42 +/- 0.56 mm was noted at 60 months. Plaque Index was consistently high
      around the abutments at all reevaluation intervals but was associated with a low
      Gingival Index. Pocket Depth averaged 2.41 +/- 0.17 mm for the entire follow-up
      period. Remarkable improvement of oral comfort and function were evidenced with
      the overdenture treatment. CONCLUSION: Rehabilitation with mandibular
      overdentures anchored to a single implant can be a therapeutic alternative for
      elderly patients experiencing discomfort and functional difficulties with
      conventional mandibular dentures.

PMID- 9260134
TI  - Clinical application of short hydroxylapatite-coated dental implants to the
      posterior mandible: a five-year survival study.
AB  - STATEMENT OF PROBLEM: The surgical and restorative procedures at the posterior
      region of the maxilla and the mandible present a complex task in the treatment of
      partially edentulous patients. PURPOSE: The purpose of this study was to
      investigate the applicability of short hydroxylapatite-coated dental implants to
      the posterior mandible of partially edentulous patients. MATERIAL AND METHODS:
      Eight and 11 mm implants were evaluated as to their cumulative survival rate,
      clinical status (plaque index, gingival index, probing depth), and marginal bone
      loss over a 5-year period. RESULTS AND CONCLUSIONS: The verified overall
      cumulative survival rate was 94% for implants and 91% for prostheses. These
      results suggest predictable success for the application of short implants to the
      posterior mandible.

PMID- 9260135
TI  - Artifacts in recording immediate mandibular translation: a laboratory
      investigation.
AB  - STATEMENT OF PROBLEM: Even though immediate mandibular translation has been
      extensively studied and analyzed, and its clinical significance emphasized, there
      is controversy as to whether it actually exists or whether it is just an artifact
      of the pantograph. PURPOSE: The aim of this study was to determine whether what
      appears to be pantographic evidence of immediate mandibular translation can
      actually be an artifact and, if so, to find a method to avoid it. MATERIAL AND
      METHODS: The first part of this article explains geometrically with computer
      vector graphics how pure rotation can produce a pantographic tracing on the
      horizontal plate that is identical to what would be seen for immediate mandibular
      translation. The second part of the article presents a technique that uses a
      modified pantograph that eliminates the rotational artifact and thus permits
      proper interpretation of true immediate mandibular translation. RESULTS: This
      study shows that pure rotation about the sagittal axis mimics immediate
      mandibular translation on a pantographic tracing when the plates are inferior to
      the transverse horizontal axis, produces scribings in an opposite direction for
      plates in a superior position, and produces no scribing when the plates are level
      with it. By modifying the pantograph so the tip of the scribing pin of the
      horizontal plate is level with the transverse horizontal axis, true immediate
      mandibular translation can most easily be differentiated from rotational
      artifact. CONCLUSIONS AND CLINICAL SIGNIFICANCE: Rotation can cause artifacts
      that mimic immediate mandibular translation. A technique to avoid this problem is
      presented. This technique provides the foundation for a valid evaluation of
      patients to determine whether true immediate mandibular translation exists and
      whether it is clinically important.

PMID- 9260136
TI  - Comparison of habitual masticatory patterns in men and women using a custom
      computer program.
AB  - STATEMENT OF PROBLEM: Though computer-based systems for recording three
      dimensional jaw motion and muscle activity during mastication are common, few
      computer programs are available to analyze the resultant data. Few studies have
      discussed the variability over time of the many parameters of the masticatory
      cycle now measurable by computer systems. PURPOSE: The purposes of this study
      were to (1) use a custom computer program, (MAS), for analysis of long-term
      repeated measurements of mandibular motion and muscle activity; (2) determine sex
      differences for mandibular movements and activity of the muscles involved during
      mastication; and (3) determine the variability over time and the statistical
      power of these methods. MATERIALS AND METHODS: Masticatory cycles of 20 normal
      men and 17 normal women were examined during mastication of a constant bolus at a
      sampling rate of 500 fps. Measurements included duration of chewing cycle and its
      component phases, mandibular displacement in three dimensions, and
      electromyographic activity in the temporalis and masseter muscles. The MAS custom
      computer program was used for analysis. Two-way repeated measures analysis of
      variance was used to compare the men with the women over three trials at 0, 6,
      and 12 months. The variability over time associated with each measurement was
      also estimated. RESULTS: Timing of the phases of the chewing cycle were most
      repeatable between trials, whereas lateral excursions and muscle force magnitudes
      were the least repeatable measures. Durations of total cycle, its slow-open and
      fast-close phases, were significantly longer for the female group, and their
      bursts of muscle activity tended to be longer. The amount of vertical mandibular
      excursion tended to be greater for men. There were no gender-related differences
      in the amplitude of muscle activity. CONCLUSIONS: This study demonstrated that
      men have significantly shorter chewing cycles with faster velocities than women.
      Men used significantly greater chewing force than women, although their
      electromyographic activity levels were equivalent. The masticatory measurements
      made by the MAS program had differing amounts of variation over time. Total
      duration of the chewing cycle and amount of opening varied the least, whereas
      amount of lateral excursion and jaw muscle electromyographic magnitudes exhibited
      the greatest variation.

PMID- 9260137
TI  - Comparison of titanium and cobalt-chromium removable partial denture clasps.
AB  - STATEMENT OF PROBLEM: The use of titanium alloys for removable partial dentures
      is an increasingly popular application. While the flexibility of titanium would
      allow for cast clasps to be placed in deeper undercuts than advisable with cobalt
      chromium, it is possible that the retentive forces of the titanium clasp might
      not maintain sufficient retention after repeated flexing of the clasp arm during
      insertion and removal of the partial denture. PURPOSE: This study assessed the
      characteristics of cast clasps made of titanium and titanium alloys to determine
      whether these materials are suitable alternatives for removable partial denture
      applications. MATERIAL AND METHODS: Removable partial denture clasps at two
      undercut depths were fabricated from commercially pure titanium, titanium alloy
      (Ti-6A1-4V), and cobalt-chromium. Loss of retention force was measured as the
      clasps underwent 3 years of simulated clinical use. The data were subjected to
      ANOVA and Scheffe's tests to determine differences. Evidence of casting defects
      and porosity was evaluated by radiographic examination and nonparametric
      statistics. SEM microscopy was used to observe surface characteristics that were
      described qualitatively. RESULTS: For the 0.75 mm undercut specimens, there was
      less loss of retention for clasps made from pure titanium and titanium alloy than
      for cobalt-chromium clasps. Porosity was more apparent in the pure titanium and
      titanium alloy clasps than in those made from cobalt-chromium, but the amount of
      porosity did not correspond to evidence of fractures or permanent deformation.
      CONCLUSIONS: The long-term retentive resiliency of the pure titanium and titanium
      alloy clasps suggests that these materials are suitable for removable partial
      dentures.

PMID- 9260138
TI  - The swelling phenomenon of acrylic resin polymer teeth at the interface with
      denture base polymers.
AB  - PURPOSE: This study examined the interface between acrylic resin polymer teeth
      and denture base polymers. MATERIAL AND METHODS: An autopolymerized denture base
      polymer was cured either at 30 degrees C, 50 degrees C, or 70 degrees C, and a
      heat-cured denture base polymer was cured at 100 degrees C in contact with
      acrylic resin polymer teeth. The specimens were ground wet and polished to a
      thickness of 0.21 mm for the examination of the interface with a light
      microscope. The surface of the specimens was then treated with the solvent
      tetrahydrofuran, and the specimens were examined with a scanning electron
      microscope (SEM). RESULTS: As a result of grinding, the inner parts of the beads
      at the interface of the teeth were exposed to the denture base polymer. The inner
      part in these polymer beads of the polymer teeth swelled to a depth of 3 microns
      when the autopolymerized polymer was cured at 30 degrees C. When cured at 70
      degrees C, the thickness of the swelled layer was 21 microns (p < 0.001).
      Microscopically, the interface between the heat-cured denture base polymer and
      the polymer teeth appeared diffuse in the region of the interpenetrating polymer
      networks (IPN) and the matrix. The IPN appeared as a separate zone in the outer
      parts of the beads of the teeth, both with the light microscope and with the SEM.
      CONCLUSIONS: The results suggest that by increasing the polymerization
      temperature, the monomers of the denture base polymers diffused more effectively
      into acrylic resin polymer teeth. This increases the bond strength between the
      polymer teeth and the denture base polymer.

PMID- 9260139
TI  - The effects of surface machining on heat cured acrylic resin and two soft denture
      base materials: a scanning electron microscope and confocal microscope
      evaluation.
AB  - STATEMENT OF PROBLEM: Rough surfaces promote the adhesion and colonization of
      denture plaque, therefore it is important to know the character of the surface
      left by rotary instruments on denture base materials. As a single microscopic
      technique can introduce artifact, complementary microscope techniques need to be
      used. PURPOSE: This study investigated the surface characteristics of the
      machined surfaces of heat-cured acrylic resin, Molloplast B and Novus. MATERIAL
      AND METHODS: Scanning electron microscopy and confocal microscopy were used to
      investigate surfaces that had been prepared with appropriate clinical rotary
      instruments. Thirty samples of each material were prepared with steel and
      tungsten carbide burs, Molloplast stones, and Arbor bands. An analysis of
      variance, with the Scheffe multiple comparison of means test, was used to compare
      average surface roughness of the individual surfaces. RESULTS: The tungsten
      carbide bur produced a smoother nongrooved surface than the steel bur on acrylic
      resin. The roughest surfaces were produced on the soft lining materials by the
      Arbor band and Molloplast stone. CONCLUSIONS: The confocal microscope is a
      valuable complementary instrument to scanning electron microscopy and provides
      surface roughness data by using a noncontact method. Each type of rotary
      instrument produces its own characteristic surface on denture base materials.

PMID- 9260140
TI  - Custom-made cover screws to fit fixed detachable implant prosthesis access
      openings.
AB  - Numerous materials have been used for closure of access openings in implant
      supported fixed detachable prostheses. This article describes an alternate
      approach to access closure by use of cast screws. Preparation of the prosthesis
      and fabrication of the access closure screw is described in detail.

PMID- 9260141
TI  - An implant-supported fixed-removable prosthesis with a milled tissue bar and
      Hader clip retention as a restorative option for the edentulous maxilla.
AB  - Restoration of the edentulous maxilla with implant retained and supported
      prosthesis is challenging because of inherent anatomic limitations present after
      the loss of teeth. A fixed-removable prosthesis is one treatment choice for
      restoration of the edentulous maxilla with implants. This prosthesis meets the
      requirements for esthetics, phonetics, comfort, and hygiene, as well as favorable
      biomechanical stress distribution to the implants. This article presents a
      procedure for fabrication of a fixed-removable prosthesis with a precision milled
      bar, Hader clip attachments, and a superstructure prosthesis. The criteria for
      patient selection and the advantages and disadvantages of this prosthesis are
      discussed.

PMID- 9260142
TI  - Ocular prosthetics: use of a tissue conditioner material to modify a stock ocular
      prosthesis.
AB  - The custom-made ocular prosthesis contributes to enhanced tissue health of the
      anophthalmic socket. For this purpose, an acrylic resin ocular prosthesis may be
      modified, by using an appropriate dental impression material and being adapted
      closely to the anophthalmic socket. The modeling impression material is
      subsequently replaced by acrylic resin. This article describes the application of
      a viscoelastic tissue conditioner material, as an impression medium for
      prosthetic modification of an ocular prosthesis. The tissue conditioner material
      exhibits favorable tissue compatibility, adhesion to acrylic resin, and detailed
      surface registration. These advantages facilitate the clinical procedure and
      evaluation of modifications made to the ocular prosthesis.

PMID- 9260143
TI  - Safe resin records using plastic copings.

PMID- 9260144
TI  - Simple and sure protection of crown margins from moisture in cementation.

PMID- 9260145
TI  - A simplified indexing procedure for presoldering fixed partial dentures.

PMID- 9260146
TI  - Acrylic resin pivot ball for the survey of mounted casts.

PMID- 9260147
TI  - HIV/AIDS: new knowledge, new treatments, and the challenges for nursing.

PMID- 9260148
TI  - HIV immunopathogenesis.
AB  - The challenges of human immunodeficiency virus type 1 (HIV-1) infection are
      related to the evolving scientific knowledge that has accumulated regarding the
      pathogenesis of the HIV illness trajectory. HIV-1 infection results in the
      clinical presentation of a disease process that encompasses a spectrum of illness
      from asymptomatic infection to acquired immune deficiency syndrome (AIDS). This
      article will provide a review of the human immune system, the structure, life
      cycle, and kinetics of HIV including its effects on the immune system, as well as
      the transmission, diagnosis, and current treatment recommendations.

PMID- 9260149
TI  - New horizons: antiretroviral therapy in 1997.
AB  - Exciting advances in basic and clinical science brought a new strategy for
      antiretroviral therapy and new hope to people living with HIV in 1996. There are
      now three major categories of antiretroviral agents available for clinical use.
      All require replicating virus, and none are virucidal. The goal of antiretroviral
      therapy is a significant and prolonged reduction of the amount of actively
      replicating HIV (viral load). Carefully chosen combinations of antiretroviral
      drugs significantly reduce HIV load and are likely to extend life. However, not
      all patients respond to highly active antiretroviral therapy (HAART), and, for
      those who do, adjustment to demanding regimens and management of side effects may
      be difficult. The development of drug resistance is a serious concern, because
      resistance is associated with rising viral loads and with poorer prognosis in
      advanced disease.

PMID- 9260150
TI  - Compliance/adherence and care management in HIV disease.
AB  - With the changing perspectives of the HIV epidemic and the introduction of
      protease inhibitors to treat human immunodeficiency virus (HIV) disease, the
      issue of compliance has gained considerable interest among health care providers.
      The idea that clients with HIV disease should succumb to a patriarchal system of
      medical care has been challenged by AIDS activists since the beginning of the
      epidemic. The concept that there is only one explanation for "noncompliance" is
      outdated. The reasons for noncompliance are multifaceted in nature and include
      psychosocial factors, complex medication and treatment regimens, ethnocultural
      concerns, and in many instances substance use. Therefore, the notion that there
      is one intervention to resolve noncompliance is at best archaic. Interventions to
      enhance compliance include supervised therapy, improving the nurse-client
      relationship, and patient education, all of which should be combined with
      ethnocultural interventions. Plans to enhance compliance must incorporate person
      specific variables and should be tailored to individualized needs.

PMID- 9260151
TI  - Errors in prescribing HIV-1 protease inhibitors.
AB  - OBJECTIVE: The purpose of this study was to describe and quantify errors in
      dosage frequency associated with written medical orders, compared to
      manufacturer's recommendations and current therapeutic recommendations for
      protease inhibitors, for persons living with HIV disease/AIDS who were receiving
      home care services. METHODS: A convenience sample was used for a univariate
      descriptive study to collect information from client records on the dosing
      intervals prescribed for three protease inhibitors: indinavir, ritonavir, and
      saquinavir. The study took place between December 1, 1996, and January 15, 1997,
      at a certified home health agency (CHHA) in New York City. The final sample
      accrued consisted of 202 adults who were receiving home care. The mean age of the
      sample was 42 years (SD = 9.43), ranging from 24 to 69 years. The majority were
      people of color, and Medicaid was the principle payor source for all health care
      needs. The main outcome measure was the number of errors in dosage frequency
      documented in written medical orders for protease inhibitors RESULTS: Protease
      inhibitors were ordered for 91 (45.1%) of the sample. Of the total number of
      medical orders for protease inhibitors, according to manufacturer's
      recommendations and current therapeutic recommendations, incorrect dosing
      schedules were noted in 36 (39.6%) of the records. Additional findings included
      errors in the dosages of drug prescribed and orders for protease inhibitors as
      monotherapy. CONCLUSIONS: Errors identified with ordering protease inhibitors
      included the incorrect frequency, the incorrect dose, and the ordering of
      protease inhibitor as a monotherapeutic agent instead of in combination with
      other recommended antiretroviral agents. Making clinicians aware of these
      problems may assist in reducing the incidence of these errors.

PMID- 9260152
TI  - Post-Vancouver: implications for nursing practice and nursing research.

PMID- 9260153
TI  - The Carnegie Institution of Washington, Department of Embryology.

PMID- 9260154
TI  - Immunotoxins for the treatment of B-cell lymphomas.

PMID- 9260155
TI  - Inhibition of astrocyte glutamate uptake by reactive oxygen species: role of
      antioxidant enzymes.
AB  - BACKGROUND: The recent literature suggests that free radicals and reactive oxygen
      species may account for many pathologies, including those of the nervous system.
      MATERIALS AND METHODS: The influence of various reactive oxygen species on the
      rate of glutamate uptake by astrocytes was investigated on monolayers of primary
      cultures of mouse cortical astrocytes. RESULTS: Hydrogen peroxide and
      peroxynitrite inhibited glutamate uptake in a concentration-dependent manner.
      Addition of copper ions and ascorbate increased the potency and the efficacy of
      the hydrogen peroxide effect, supporting the potential neurotoxicity of the
      hydroxyl radical. The free radical scavenger dimethylthiourea effectively
      eliminated the inhibitory potential of a mixture containing hydrogen peroxide,
      copper sulphate, and ascorbate on the rate of glutamate transport into
      astrocytes. The inhibitory effect of hydrogen peroxide on glutamate uptake was
      not altered by the inhibition of glutathione peroxidase, whereas the inhibition
      of catalase by sodium azide clearly potentiated this effect. Superoxide and
      nitric oxide had no effect by themselves on the rate of glutamate uptake by
      astrocytes. The absence of an effect of nitric oxide is not due to an inability
      of astrocytes to respond to this substance, since the same cultures did respond
      to nitric oxide with a sustained increase in cytoplasmic free calcium.
      CONCLUSION: These results confirm that reactive oxygen species have a potential
      neurotoxicity by means of impairing glutamate transport into astrocytes, and they
      suggest that preventing the accumulation of hydrogen peroxide in the
      extracellular space of the brain, especially during conditions that favor
      hydroxyl radical formation, could be therapeutic.

PMID- 9260156
TI  - Differential regulation of the p21/WAF-1 and mdm2 genes after high-dose UV
      irradiation: p53-dependent and p53-independent regulation of the mdm2 gene.
AB  - BACKGROUND: DNA damage in mammalian cells stabilizes the p53 protein which then
      functions as a cell cycle checkpoint by leading to growth arrest or apoptosis.
      p53 is a transcription factor and positively regulates the expression of the
      p21/WAF-1 gene and the mdm2 gene. After high-dose UV irradiation, p53 increases
      the expression of the p21/WAF-1 gene immediately (2 to 5 hours after irradiation)
      while the induction of the mdm2 gene is delayed (8 to 12 hours after
      irradiation). Experiments presented here explore this differential expression of
      two different p53-regulated genes. MATERIALS AND METHODS: IP-Western (protein)
      and Northern (mRNA) blot experiments are used to follow mdm2 and p21/WAF-1
      expression in primary rat or mouse cells after a low-dose (4 J/m2) or a high-dose
      (20 J/M2) of UV irradiation. Northern blot and nuclear run-on experiments are
      employed to study mRNA stability as well as transcription rates of selected
      genes. RESULTS: After high-dose UV irradiation, p53 is rapidly stabilized and the
      expression of p21/WAF1 is immediately increased. By contrast, both protein and
      mRNA levels of mdm2 first decrease in a p53-independent manner, and later
      increase in a p53-dependent manner. The initial decline of mdm2 expression
      following high-dose UV irradiation is UV-dosage dependent and regulated at the
      level of transcription. CONCLUSION: p53 regulates two genes, p21/WAF1 (blocks
      cell cycle progression) and mdm2 (reverses p53 activity), that mediate opposite
      actions. This process is regulated in a temporal fashion after high-dose UV
      irradiation, so that cell cycle progression can be halted while DNA repair
      continues prior to reversal of p53-mediated arrest by mdm2.

PMID- 9260157
TI  - Multiple mechanisms support oligoclonal T cell expansion in rheumatoid synovitis.
AB  - BACKGROUND: The synovial T cell infiltrate in rheumatoid arthritis (RA) is
      diverse but contains clonally expanded CD4+ populations. Recent reports have
      emphasized that RA patients have a tendency to develop CD4+ T cell oligoclonality
      which also manifests in the peripheral blood. Clonal dominance in the tissue may
      thus result from antigen specific stimulation in the synovial membrane or may
      reflect the infiltration of expanded clonotypes present throughout the lymphoid
      system. We have explored to what extent clonal populations amongst tissue CD4+ T
      cells display joint specificity as defined by their restriction to the joint,
      their persistence over time, and their expression of markers indicative for local
      activation. MATERIALS AND METHODS: Matched samples of peripheral blood and
      synovial fluid or synovial tissue were collected from 14 patients with active RA
      and CD4+ IL-2R+ and CD4+ IL-2R- T cells from both compartments were purified.
      Clonal populations of CD4+ T cells were detected by RT-PCR amplification of T
      cell receptor (TCR) transcripts with BV and BJ specific primers followed by size
      fractionation and direct sequencing of dominant size classes of TCR transcripts.
      RESULTS: Clonal CD4+ T cells were detected in the synovial fluid and synovial
      tissue of all patients. All patients carried synovial clonotypes that were
      undetectable in the blood but were present in independent joints or at several
      non-adjacent areas of the same joint. These joint restricted CD4+ clonotypes were
      generally small in size, were preferentially found in the IL-2R+ subpopulation,
      and persisted over time. A second type of clonogenic T cells in the synovial
      infiltrate had an unrestricted tissue distribution and was present at similar
      frequencies amongst activated and nonactivated T cells in the blood and affected
      joints. Ubiquitous clonotypes isolated from two different patients expressed
      sequence homologies of the TCR beta chain. CONCLUSIONS: Two types of expanded
      CD4+ clonotypes contribute to the T cell infiltrate in rheumatoid synovitis.
      Differences in the distribution pattern and in molecular features suggest that
      distinct mechanisms are supporting the clonal outgrowth of these two groups of
      clonotypes. Clonally expanded T cells restricted to the joint but present in
      several independent joints appear to respond to locally residing antigens.
      Clonogenic cells with an unrestricted distribution pattern and widespread
      activation in the blood and tissue may react to a different class of antigens
      which appear to be shared by multiple patients. T cell recognition in RA may be
      involved at several different levels and may be related to more than one
      pathomechanism.

PMID- 9260158
TI  - Versatile retrovirus vector systems for regulated gene expression in vitro and in
      vivo.
AB  - BACKGROUND: Several plasmid DNA-based mammalian expression systems have recently
      been developed which make it possible to manipulate gene expression via the
      administration of exogenous agents. In order to extend the application of these
      systems, we have developed retroviral vectors which allow for the controlled
      expression of inserted genes both in vitro and in vivo. MATERIALS AND METHODS:
      Two vector strategies which make use of the tetracycline-regulated gene
      expression system described by Gossen and Bujard were evaluated. In a first
      strategy, one virus was generated which encoded the tTA or rtTA transactivator
      gene product, and a second virus was generated in which expression of the gene of
      interest was dependent upon tetracycline-responsive transcriptional control
      elements placed either within the viral LTR or within the proviral
      transcriptional unit. In a second vector strategy, both components of the tet
      regulatable system were incorporated into a single proviral genome in such a way
      that expression of both the transgene and the transactivator gene product were
      under control of tet-regulatable control elements. RESULTS: Both vector
      strategies resulted in the ability to regulate the expression of inserted genes.
      In one single virus configuration, gene expression could be regulated over 100X
      and the level of gene expression in the induced state was comparable to or
      greater than that achieved with standard LTR-based vectors. The use of different
      deletions in the viral LTR made it possible to generate a number of vectors which
      provide for a four-fold range of levels of expression of inserted genes in the
      induced state. Studies in mice with transduced cells demonstrated that gene
      expression could be induced in vivo by manipulation of tetracycline for at least
      48 days. CONCLUSIONS: The availability of highly transmissible, regulatable
      retroviral vectors should greatly facilitate studies in which it is of interest
      to manipulate the expression of specific genes in vitro or in vivo.

PMID- 9260160
TI  - Electromyography in myopathy.
AB  - Electromyography (EMG) is the most common procedure for screening patients with
      myopathies and remains the most important technique for assessing the course of
      the disease over time. Fibrillation potentials, positive sharp waves, myotonic or
      complex repetitive discharge, as well as polyphasic potentials are non specific
      and can occur in both myopathic and neurogenic lesions. The most sensitive and
      specific parameter for myopathy in conventional EMG is the decreased duration of
      motor unit potentials (MUP), but this can also be seen in disorders of the
      terminal motor fibers or the neuromuscular junction. More advanced techniques
      such as single fiber EMG, macro EMG, scanning EMG and turns/amplitude analysis
      have opened additional possibilities for analysis of the motor unit and the
      interference pattern, by which both the sensitivity to early changes and
      specificity for myopathic alterations is increased. The importance of combining
      different techniques to improve diagnostic yield and specificity is stressed.

PMID- 9260159
TI  - Molecular and structural characterization of five novel mutations in the Bruton's
      tyrosine kinase gene from patients with X-linked agammaglobulinemia.
AB  - BACKGROUND: The Btk (Bruton's tyrosine kinase) gene has been shown to be mutated
      in the human immunodeficiency disease, XLA (X-linked agammaglobulinemia). Btk is
      a member of the Tec family of cytosolic protein tyrosine kinases with distinct
      functional domains PH, TH, SH3, SH2, and kinase. Mutations have been observed in
      each of the Btk subdomains in XLA. We have analyzed the Btk gene in six XLA
      patients from five unrelated families. MATERIALS AND METHODS: DNA was prepared
      from the patients peripheral blood. The Btk exons including the junctional
      sequences were analyzed by single-strand conformation polymorphism (SSCP)
      followed by direct nucleotide sequencing after PCR-amplification. For structural
      analysis, the missense mutations were introduced into three-dimensional models of
      the PH and kinase domains of Btk and the outcome was predicted based on the
      knowledge of the protein function. RESULTS: Five novel mutations and two novel
      polymorphisms, all of which resulted from single-base alterations, were
      identified. Three of the five mutations were in the PH domain and two were in the
      kinase domain of Btk. Three of these mutations were of the missense type, two of
      which altered the same codon in the PH domain; the third one was located in the
      kinase domain. The fourth mutation was a point deletion in the PH domain causing
      a frameshift followed by premature termination. The fifth mutation was a splice
      donor-site mutation within the kinase domain which could result in an exon
      skipping. In four of the five instances, mothers of the patients were shown to be
      obligate carriers. In one instance, a sibling sister was identified as a
      heterozygote establishing her as a carrier. CONCLUSIONS: Functional consequences
      of the mutations causing frameshifts and altered splicing can be inferred
      directly. Functional consequences of the missense mutations were interpreted by 3
      dimensional structural modeling of Btk domains. It is proposed that the two PH
      domain mutations will interfere with membrane localization while the kinase
      domain mutation will interfere with the enzymatic function of Btk. This study
      provides further insight into the role of Btk in XLA.

PMID- 9260161
TI  - Electromyogram, evoked sensory and motor potentials in neurourology.
AB  - To test the integrity of the sacral neuromuscular system, the concentric needle
      electromyogram (EMG) is suggested as the established method to provide
      information on denervation and reinnervation. The electrophysiologically recorded
      bulbocavernosus reflex is more sensitive than the clinically performed test; its
      latency is, however, not a sensitive test to assess axonal lesions. Pudendal
      cerebral somatosensory evoked potentials (SEP) can be considered promising in
      patients with conus involvement. Motor evoked potentials (MEP) in perineal
      muscles can only be considered investigational. True sensitivity and specificity
      of uroneurophysiological tests is difficult to establish due to the lack of a
      'gold standard' test to define the underlying neurological lesion. Therefore,
      good (age stratified) reference values have to be established.

PMID- 9260162
TI  - The role of the electroencephalogram in the diagnosis of dementia of the
      Alzheimer type: an attempt at technology assessment.
AB  - In a first attempt at technology assessment of the electroencephalogram (EEG) in
      the diagnosis of patients with Alzheimer's disease (AD), three conclusions were
      reached: notwithstanding the well defined clinical criteria, there remains a need
      for a laboratory technique to confirm the diagnosis since a 100% accuracy cannot
      be obtained by clinical methods only; although the EEG has a high sensitivity in
      separating AD patients from normal controls, the sensitivity of the EEG is at
      present not satisfactory when studying populations with a low prevalence of AD
      patients; the sensitivity of the EEG is higher or equal to the best other
      laboratory techniques (magnetic resonance imaging [MRI], computerized tomography
      [CT], SPECT, PET) available at the moment. Since the EEG and MRI can be helpful
      in different aspects of the differential diagnosis it is argued that all AD
      patients should be studied at least once by EEG as well as by MRI.

PMID- 9260163
TI  - The social context of substance abuse: a developmental perspective.

PMID- 9260164
TI  - The special nature of rural America.

PMID- 9260165
TI  - Drug and alcohol use among youth in rural communities.

PMID- 9260166
TI  - Traffic and illegal production of drugs in rural America.

PMID- 9260167
TI  - Risk and protective factors for drug use among rural American youth.

PMID- 9260168
TI  - Health consequences of alcohol use in rural America.

PMID- 9260169
TI  - Health consequences of rural illicit drug use: questions without answers.

PMID- 9260170
TI  - Social and economic consequences of rural alcohol use.

PMID- 9260171
TI  - The economic and social costs of drug abuse among the rural population.

PMID- 9260172
TI  - The prevention of alcohol use by rural youth.

PMID- 9260173
TI  - A drug abuse prevention strategy for rural America.

PMID- 9260174
TI  - In living context: an interdisciplinary approach to rethinking rural prevention.

PMID- 9260175
TI  - Mental health service delivery in rural areas: organizational and clinical
      issues.
AB  - The mental health funding cuts and the block grant shift of the last decade have
      placed an increased emphasis on fee-generating services. In already underserved
      rural areas, this has generated immense challenges for mental health
      professionals on how to provide services to persons other than those with chronic
      mental illness. This chapter has discussed alternatives and innovations that have
      proven successful. Linkages with primary care physicians and indigenous residents
      who have been trained to provide basic mental health services under the
      supervision of mental health professionals are just two of the ways in which
      mental health professionals have risen to meet the challenges placed before them.
      A review of the literature produced few articles about rural programs addressing
      the issues of substance abuse, services to women, children, the elderly, those
      with severe mental illness or developmental disability, and the homeless, or
      crisis intervention programs. Much work needs to be done to provide adequate
      services to these special rural populations. It is hoped that the renewed
      interest in rural areas generated by the farm crisis will produce additional
      programs addressing the needs of these often underserved populations.

PMID- 9260176
TI  - Alcohol and drug abuse by migrant farmworkers: past research and future
      priorities.

PMID- 9260177
TI  - Culturally competent substance abuse prevention research among rural Native
      American communities.

PMID- 9260178
TI  - Substance abuse in rural African-American populations.

PMID- 9260179
TI  - Drug and alcohol use among rural Mexican-Americans.

PMID- 9260180
TI  - The potential role of the cytochrome P-450 2D6 pharmacogenetic polymorphism in
      drug abuse.

PMID- 9260181
TI  - Human liver cocaine carboxylesterases.

PMID- 9260182
TI  - Effects of ethanol on cocaine metabolism and disposition in the rat.

PMID- 9260183
TI  - Individual differences in nicotine kinetics and metabolism in humans.
AB  - Individual differences in susceptibility to nicotine addiction, the likelihood of
      successful smoking cessation, and the development of adverse health effects of
      smoking are well recognized. The basis for these individual differences is as yet
      unknown. This chapter examines individual differences in the metabolism and
      kinetics of nicotine as a possible factor. Rare individuals appear to be
      deficient metabolizers of nicotine. Individual differences are described both in
      the pattern and rates of nicotine metabolism. Ethnic differences in cotinine
      metabolism have also been observed. However, the enzymes responsible for nicotine
      metabolism and their genetic regulation have not been fully characterized.
      Understanding the basis for individual differences in nicotine kinetics and
      metabolism, and linking these differences to pharmacodynamic studies, may provide
      important clues for the prevention and treatment of nicotine and possibly other
      drug addictions.

PMID- 9260184
TI  - Inhibitors of anandamide breakdown.

PMID- 9260185
TI  - Metabolic bioactivation reactions potentially related to drug toxicities.

PMID- 9260186
TI  - The role of iminium-enamine species in the toxication and detoxication of cyclic
      tertiary amines.

PMID- 9260187
TI  - Neurotoxicity of amphetamines and their metabolites.

PMID- 9260188
TI  - Potential new insights into the molecular mechanisms of methamphetamine-induced
      neurodegeneration.
AB  - In the event that methamphetamine evokes HO. formation within serotonergic axon
      terminals, the resultant oxidation of 5-HT would be expected to generate not only
      5,6-DHT but also T-4,5-D, 7-S-Glu-T-4,5-D, 6, 8, and 7,7'-D (figure 1), at least
      three of which (T-4,5-D, 7-S-Glu-T-4,5-D, and 6) are lethal in mouse brain.
      Furthermore, several intermediates/products formed in the in vitro oxidation of 5
      HT by HO. are readily autoxidized (4,5-DHT, 5,6-DHT, 5, 7, and 9) or redox cycled
      (T-4,5-D, 6, 8, 7,7'-D, 7-S-Glu-T-4,5-D) in reactions that would be expected to
      yield O2-. and/or H2O2 as byproducts. These byproducts, in the presence of trace
      levels of transition metal ion catalysts, would be readily converted into HO.
      (Walling 1975; Halliwell and Gutteridge 1984). Together these putative aberrant
      oxidative metabolites of 5-HT and HO.-forming reactions might contribute to the
      degeneration of serotonergic nerve terminals. Similarly, the methamphetamine
      induced intraneuronal formation of HO. in dopaminergic terminals might be
      expected to generate not only 6-OHDA (and 2-OHDA and 5-OHDA, figure 3) but also
      5,-S-CyS-DA and 5-S-Glu-DA, precursors of DHBT 17 and other more complex
      dihydrobenzothiazines (figure 4). DHBTs 17 to 19 are lethal in mouse brain,
      although at this time the biochemical/chemical mechanisms underlying this
      toxicity and specific neuronal systems affected are unknown. However, 5-S-CyS-DA
      and 17 to 19 are much more easily oxidized than DA, and the latter DHBTs appear
      to be capable of redox cycling reactions (Zhang and Dryhurst 1994). Thus, the HO.
      mediated oxidation of DA in dopaminergic nerve terminals induced by
      methamphetamine might be expected to generate aberrant oxidative metabolites that
      (as a result of autoxidation and redox cycling reactions) potentiate formation of
      O2-. and/or H2O2, and then HO. and neuronal damage. A number of lines of
      evidence, discussed previously, suggest that aberrant metabolite(s) of DA (other
      than or in addition to 6-OHDA) might contribute to the methamphetamine-induced
      degeneration of not only dopaminergic terminals but also serotonergic terminals.
      Similarly, aberrant metabolite(s) of 5-HT (other than or in addition to 5,6-DHT)
      might be involved in the degeneration of serotonergic and dopaminergic terminals
      and a subpopulation of cell bodies in the somatosensory cortex. Experimental
      evidence indicates that some of the neurodegenerative effects evoked by
      methamphetamine are mediated by NMDA and GABA receptors. Thus, it will be of
      considerable interest to investigate the neurotoxicity of putative aberrant
      oxidative metabolites of 5-HT (figures 1 and 2) and DA (figures 4 and 5) towards
      serotonergic, dopaminergic, and other neuronal systems and their interactions
      with NMDA, GABA, and other brain receptors. A central question relates to
      mechanisms by which methamphetamine might evoke the intraneuronal formation of
      oxygen radicals that appear to play important roles in the overall
      neurodegenerative processes evoked by this drug (DeVito and Wagner 1989; Cadet et
      al. 1994). Once putative oxidative metabolites of 5-HT such as T-4,5-D, 7-S-Glu-T
      4,5-D, 5,6-DHT, 6, 8, and 7,7'-D (figure 1) are formed intraneuronally,
      autoxidation/redox cycling reactions should, in principle, be capable of
      generating O2-. and/or H2O2, the precursors of HO.. Similarly, intraneuronal
      formation of 6-OHDA, 5-S-CyS-DA, and DHBTs 17 to 19 and 22 would also be expected
      to potentiate elevated fluxes of O2-., H2O2, and HO. as a result of the facile
      autoxidation/redox cycling reactions of these putative aberrant metabolites. The
      presence of very low concentrations of 5-S-CyS-DA in DA-rich regions of human and
      other mammalian brains suggest that autoxidation (Rosengren et al. 1985;
      Fornstedt et al. 1986, 1989, 1990) or perhaps some other form of DA oxidation is
      a normal reaction in vivo. Furthermore, available evidence suggests that it is
      cytoplasmic DA that is oxidized to give 5-S-CyS-DA (Fornstedt et al. 1989;
      Fornstedt and

PMID- 9260189
TI  - Immunotoxicology of opioids, inhalants, and other drugs of abuse.

PMID- 9260190
TI  - Inhalation studies with drugs of abuse.

PMID- 9260191
TI  - Biocatalysts in detoxication of drugs of abuse.
AB  - Currently there is a significant amount of information about the way biocatalysts
      from animals detoxicate and bioactive drugs of abuse. In some cases,
      biotransformation data concerning drugs of abuse obtained from animal systems are
      analogous to the human situation, but in many cases the data are not. Clearly,
      significant work needs to be done with human biocatalysts to define a role in the
      biotransformation of drugs of abuse and to relate the work that has already been
      done in animals. New metabolic pathways will likely be discovered that may link
      drug metabolism to addiction liability or drug susceptibility in humans. New
      design and selection technologies are providing the basis to allow the discovery
      of new biocatalysts that may be useful in the detoxication of drugs of abuse in
      humans. Fundamentally new approaches using biocatalysts including rationally
      engineered enzymes, catalytic antibodies, catalytic antibody fragments,
      ribozymes, oligonucleotides, and other biomacromolecules may provide basic
      information that may later support the rational design of biocatalysts, which may
      in turn provide the basis for designing detoxication catalysts for drugs of
      abuse.

PMID- 9260192
TI  - Antibodies as pharmacokinetic and metabolic modifiers of neurotoxicity.

PMID- 9260193
TI  - Toxicokinetics in the National Toxicology Program.
AB  - Toxic responses to test chemicals are known to be dependent on the exposure
      route, the kinetic behavior of the chemical, and the dose used in the toxicology
      study. Therefore, knowledge of internal dose is indispensable for the
      interpretation of toxicology study results, for the facilitation of interspecies
      scaling, and for risk assessment. By monitoring the blood and/or tissue
      concentrations of test chemical and/or metabolites versus time after
      administration of study chemicals by different routes, the bioavailability and
      kinetic characteristic of test chemicals can be readily obtained. This data can
      define the so-called linear dose range using area under the plasma concentration
      versus time curve, clearance, or other related toxicokinetic parameters, and can
      also be used to predict the possible bioaccumulation under multiple dose regimes.
      Changes in kinetic parameters after multiple exposures indicate alteration in how
      the animal handles the chemical (e.g., that there was enzyme induction or
      inhibition). A recommended approach for conducting toxicokinetic studies
      generally involves three steps. Step 1 is a preliminary study, which uses a
      minimum number of animals to estimate the range of blood/tissue concentrations,
      the required quantitation limit for the analytical method, and the optimal
      sampling times for the definitive toxicokinetic studies. Step 2 is the definitive
      study and generates blood and/or tissue concentration data for calculating the
      toxicokinetic parameters. Step 3 is the toxicokinetic study conducted in
      conjunction with the toxicology study to determine the internal dose and the
      effects of age and continuous exposure on kinetic parameters. Examples of the
      application of NTP toxicokinetic evaluations were also presented in this chapter,
      demonstrating their use in the design and interpretation of toxicology studies.

PMID- 9260194
TI  - Effect of green tea catechins on the amount of 8-hydroxydeoxyguanosine (8-OHdG)
      in pancreatic and hepatic DNA after a single administration of N-nitrosobis(2
      oxopropyl)amine (BOP).
AB  - Effects of green tea catechins on N-nitrosobis(2-oxopropyl)amine (BOP)-induced
      oxidative stress in pancreas and liver were examined. Hamsters were divided into
      two groups: one group was given free access to a 0.1% solution of green tea
      catechins as drinking water (c-ham) and the other to plain tap water (w-ham) for
      1 week before subcutaneous injection of BOP 20 mg/kg body weight. Zero, 1, 2, 6,
      12, 24, and 48 h after BOP injection, the pancreas and liver were excised and the
      tissue concentration of lipid peroxides (TBA values) and the amount of 8
      hydroxydeoxyguanosine (8-OHdG) in nuclear DNA were measured. The concentration of
      lipid peroxides and the amount of 8-OHdG in the pancreas showed similar patterns
      of change between c- and w-ham. Soon after BOP injection, the concentration of
      lipid peroxides and the amount of 8-OHdG increased with a peak at 1 and 6 h,
      respectively. Their peak values of c-ham were significantly depressed compared
      with those of w-ham. Both levels returned to steady-state levels by 24 h. In the
      liver, the concentration of lipid peroxides and the amount of 8-OHdG were not
      affected by BOP administration. These results suggest that BOP induces oxidative
      damages in the target organ and oral intake of green tea catechins has a
      protective effect on the oxidative stress.

PMID- 9260195
TI  - Proinsulin and its conversion intermediates in human pancreas and isolated islet
      tissue: kinetics and steady-state analysis.
AB  - In non-insulin-dependent diabetes, circulating insulin-related immunoreactivity
      (IRI) is often composed of a higher fraction of the incompletely converted forms
      proinsulin and des-31,32 proinsulin. The present study describes an
      immunoadsorption method for measuring the proportions of proinsulin, its two
      split products, and insulin in human pancreatic tissue and for determining their
      rates of formation in human isolated islets. The method uses two junction
      specific monoclonal proinsulin antibodies in a protein G fractionation; it is
      validated by > or = 90% specificity and recovery. The peptide contents measured
      in tissue extracts were comparable to those determined in a previously developed
      immunoradiometric assay. In the nine tissue extracts from nondiabetic donor
      organs, 97% of IRI corresponded to insulin, 1% to proinsulin, 2% to the des-31,32
      proinsulin conversion product, and 0.1% to des-64,65 proinsulin. Two samples from
      non-insulin-dependent diabetics under sulfonylurea treatment contained a fourfold
      lower content of IRI but the peptide distribution was comparable except for a low
      percentage (0.3) of proinsulin in one case. In pulse-chase experiments on three
      preparations of human islets isolated from nondiabetic donors, proinsulin
      represented the major (> 90%) IRI that was synthesized at the end of the 30-min
      pulse; a subsequent 90-min chase at either 2.5 or 10 mM glucose resulted in
      conversion of 75% of proinsulin to des-31,32 (20%) and des-64,65 (2%)
      intermediates and to insulin (50%); after a 180-min chase, 88% of proinsulin was
      converted to insulin, but 10% remained present as proinsulin. In a pulse-chase
      experiment on islets isolated from tissue with a high proportion of des-31,32
      intermediate (5% instead of 2%), the conversion process was slower (45% after 90
      min and 70% after 180 min) and resulted in a higher fraction of des-31,32
      intermediate, suggesting that the elevated tissue content in this intermediate is
      caused by a reduced PC2 converting activity. These data confirm that des-31,32
      proinsulin represents the major conversion intermediate in normal human islets
      and indicate the existence of slow converters, possibly as a result of decreased
      enzymatic processing of the prohormone's AC junction.

PMID- 9260196
TI  - Effects of all-trans-retinoic acid (ATRA) and retinoic acid receptor (RAR)
      expression on secretion, growth, and apoptosis of insulin-secreting RINm5F cells.
AB  - To define the functions of retinoids and their receptors in insulin secretion, we
      tested the effects of all-trans-retinoic acid (ATRA) and retinoic acid receptor
      (RAR) expression on cell growth, differentiation, and secretion using insulin
      secreting RINm5F cells. Wild-type cells with a low abundance of mRNA for RAR beta
      were transfected with RAR beta or chloramphenicol acetyltransferase (CAT
      control). Cells were cultured for 2-7 days in media without (A-def) or with ATRA,
      1, 10, 100, and 1,000 nM. At day 2 of culture, ATRA stimulated insulin release in
      wild-type and transfected cells, and this effect was dose dependent. At 7 days,
      ATRA stimulated insulin secretion from wild-type cells twofold at glucose
      concentrations of 0.5 mM (A-def, 5.1 +/- 0.27; ATRA, 1,000 nM, 10.5 +/- 1.43
      ng/10(6) cells) and at 11.0 mM (A-def, 6.9 +/- 0.24; ATRA, 1,000 nM, 13.6 +/-
      1.86 ng/10(6) cells). The cellular insulin content was increased about threefold
      (A-def, 39.2 +/- 2.95; ATRA, 1,000 nM, 118 +/- 8.54 ng/10(6) cells). ATRA
      inhibited growth of wild-type cells as early as 3 days, and this effect was dose
      dependent. Whereas in the absence of ATRA, the cell number increased over
      fivefold between day 3 and day 5, ATRA, 1,000 nM, inhibited cell growth
      completely. ATRA, 1,000 nM, increased apoptotic RINm5F cells (day 3 A-def, 0.53
      +/- 0.27% of total cells, and ATRA, 2.30 +/- 1.44; day 5 A-def, 0.38 +/- 0.23,
      and ATRA, 2.14 +/- 0.59; day 7 A-def, 0.90 +/- 0.29, and ATRA, 6.02 +/- 1.64).
      RAR beta-transfected cells showed overexpression of mRNA to RAR beta and dose
      dependent inhibition of growth, with almost-complete inhibition at ATRA
      concentrations as low as 100 nM. Overexpression of RAR beta increased insulin
      secretion at ATRA, 100-1,000 nM. In summary, ATRA increased the insulin secretion
      and content of RINm5F cells, while inhibiting growth and increasing apoptosis.
      Increased expression of RAR beta facilitated these effects on growth and
      secretion. These findings may reflect the known effect of ATRA on differentiation
      of cells and mediation through RAR beta.

PMID- 9260197
TI  - An unidentified pancreatic cancer cell product alters some intracellular pathways
      of glucose metabolism in isolated rat hepatocytes.
AB  - In this study we assessed whether conditioned media from a human pancreatic
      cancer cell line (MIA PaCa 2) can interfere with some intracellular pathways
      involved in glucose metabolism in isolated rat hepatocytes. The hepatocytes,
      isolated from Male Wistar rats, were incubated with MIA PaCa 2-conditioned or
      nonconditioned media. Conditioned and nonconditioned hepatocytes were run for 120
      min in the presence or absence of insulin (100 mM) and were sampled at fixed time
      intervals. Supernatant glucose levels decreased to a similar extent over time in
      both conditioned and nonconditioned hepatocytes, while lactate levels
      significantly increased in nonconditioned hepatocytes with respect to conditioned
      hepatocytes. A pyruvate kinase activity increase was observed only in
      nonconditioned hepatocytes and was biphasic in nature, since this increased
      activity was detected both after a few and after 30 min following insulin
      stimulation. The cyclic AMP level increase was significantly higher in
      conditioned than in nonconditioned hepatocytes. It appears that MIA PaCa 2 cells
      produce a factor(s) that may interfere with one of the insulin-mediated
      intracellular pathways of glucose metabolism, namely, glycolysis. This
      detrimental effect on glycolysis is supported by the blunted rise in lactate
      concentration in the medium after the glucose challenge. This substance(s)
      probably transfers its signal inside the target cells, activating the adenylate
      cyclase pathway. These results support the hypothesis that pancreatic cancer is
      the cause rather than the consequence of diabetes mellitus.

PMID- 9260198
TI  - Immunohistochemical differentiation of monoclonal GAD antibodies recognizing
      linear or conformational epitope regions.
AB  - GAD65 is targeted by different patterns of autoantibodies [glutamic acid
      decarboxylase (GAD)-AAbs] in insulin-dependent diabetes mellitus (IDDM) and stiff
      man syndrome (SMS). To study differentiation of the GAD-AAb pattern by
      immunohistochemistry, we examined the immunostaining of 15 monoclonal GAD
      antibodies (mc-GAD-Abs), which recognized different epitope regions of the
      antigen, on human pancreatic sections that were unfixed or fixed with different
      fixatives. By a competitive sandwich enzyme-linked immunosorbent assay (ELISA),
      three binding patterns of mc-GAD-Abs were identified: 5 of 15 mc-GAD-Abs
      recognized a linear N-terminal epitope (p1), 5 of 15 were reactive with a
      conformational GAD65 epitope region (p2), and 5 of 15 were cross-reactive with
      GAD67 (p3). These patterns of mc-GAD-Abs were tested for islet cell binding by
      indirect immunofluorescence on pancreatic sections treated with either (1)
      Bouin's solution, (2) Zamboni's solution, or (3) phosphate-buffered formaldehyde
      for 0.5, 1, 2, and 18 h at 4 degrees C. After fixation for up to 2 h no
      differentiation of immunoreactivity of patterns was observed using the three
      fixatives. mc-GAD-Abs recognizing conformational epitope regions (p2) revealed a
      marked reduced immunoreactivity on pancreatic sections fixed for 18 h with 4%
      formaldehyde, while mc-GAD-Abs reactive with linear epitopes (p1, p3) were
      detectable with strong binding. This fixation procedure was used to compare the
      immunoreactivity of GAD-AAb+ or GAD-AAb- islet cell cytoplasmic antibody-positive
      (ICA+) sera of IDDM (n = 27) and SMS patients (n = 3). The three SMS sera were
      reactive with GAD on fixed islets but showed a reduced titer, whereas the
      majority of IDDM sera (22/27; 81.5%) were not detectable; 70.6% (12/ 17) of GAD
      AAb+ IDDM sera were not detectable on fixed islets. Furthermore, all 10 GAD-AAb-
      IDDM sera tested failed to react with fixed pancreas, which also suggested an
      alteration of non-GAD-ICA antigens. In conclusion, the fixation of human
      pancreatic sections with formaldehyde for 18 h allows the differentiation of GAD
      AAbs recognizing linear and conformational epitope regions.

PMID- 9260199
TI  - Total parenteral nutrition influences both endocrine and exocrine function of rat
      pancreas.
AB  - The aim of this study was to examine the effect of total parenteral nutrition
      (TPN) on the endocrine and exocine function of the pancreas. Endocrine function
      was investigated using an intravenous glucose tolerance test (IGTT) in rats with
      TPN for 7 or 14 days. Exocrine function was evaluated by measuring amylase
      secretion from isolated acini as well as pancreatic weight, water content,
      protein, and enzymes after 7 days of TPN. When the TPN rats were compared with
      the controls, the glucose tolerance curve after an IGTT was unchanged, the basal
      plasma insulin levels were slightly lower and the insulin secretory response to
      intravenous glucose was markedly impaired. No differences could be seen between
      the insulin response after 7 days and that after 14 days of TPN. The weight of
      pancreas, the total content and concentration of pancreatic protein, and the
      total amylase content of the pancreas were lower, whereas the total content of
      both chymotrypsin and trypsin was higher. The concentration of DNA remained
      intact, whereas the total DNA content decreased. The levels of lipolytic enzymes,
      except for carboxylesterlipase, were unaffected. After TPN treatment, the insulin
      secretory response to glucose is impaired, the exocrine pancreas is hypoplastic
      and the storage pattern of pancreatic exocrine enzymes is altered.

PMID- 9260200
TI  - Early lymphatic tumor cell dissemination in pancreatic cancer: frequency and
      prognostic significance.
AB  - Tumor relapse occurs frequently in patients with ductal pancreatic head cancer
      despite the absence of residual tumor detectable at primary surgery. Therefore it
      has to be assumed that current tumor staging procedures fail to detect minimal
      amounts of disseminated tumor cells present in secondary organs, which might be
      the seed for subsequent metastatic relapse. We evaluated lymph nodes from 18
      patients without overt metastases who had undergone radical tumor resection (R0
      resection). Lymph nodes judged as "tumor-free" by routine histopathology were
      further examined for the presence of single tumor cells using
      immunohistochemistry with the antiepithelial monoclonal antibody Ber-EP4. Sixteen
      of 37 "tumor-free" lymph nodes (43.2%), obtained from 13 of 18 patients (72.2%),
      displayed Ber-EP4+ tumor cells. Twelve of these 18 patients presented at pT2
      stage. Nine of 12 patients (75%) staged as pN0 had these cells. Two of six pN1
      patients had no Ber-EP4+ in histopathologically tumor-free lymph nodes. Using
      multivariate Cox's regression analysis, the presence of Ber-EP4+ cells in "tumor
      free" lymph nodes was an independent factor for a significantly reduced relapse
      free survival (p = 0.006) and overall survival (p = 0.01). Remarkably, all
      patients who were restaged as lymph node negative by both histopathology and
      immunohistochemistry survived the observation period without recurrence. The
      frequent occurrence of disseminated tumor cells in patients with pancreatic
      cancer and their prognostic impact support the need for a refined staging system
      of excised lymph nodes, which should include immunohistochemical examination.
      Thus patients with a minimal residual tumor load who might benefit from an
      adjuvant therapy could be selected.

PMID- 9260201
TI  - Expression of the protooncogene jun is induced in the rat pancreas by cerulein
      infusion.
AB  - Cholecystokinin (CCK) can stimulate secretion and DNA synthesis in pancreatic
      acinar cells. Hyperstimulation with cerulein (a CCK analogue) induces acute
      edematous pancreatitis. To study the effects of in vivo pancreatic stimulation
      with cerulein, we analyzed the expression of the protooncogenes jun, myc, and fos
      on the mRNA and protein levels. RNA and protein were extracted from the pancreas
      of rats administered an infusion of cerulein, 10 micrograms/kg/h (Group A) or
      0.25 microgram/kg/h (Group B), or saline (Group C) and sacrificed 2, 4, and 6 h
      after beginning the infusion and 0, 12, and 24 h and 2, 4, and 6 days after
      completing the infusion period. Transcript levels were studied using slot-blot
      analysis. Protein expression was studied using Western blot and
      immunohistochemistry. No changes were found for the expression of protooncogenes
      myc and fos on either the transcript or the protein levels. Higher jun mRNA
      levels were found in Group A than in Group B or C, particularly after 2 h of
      infusion and 12, 24, and 48 h after the end of a 12-h cerulein infusion. No
      significant difference was observed in Groups B and C. The jun protein behavior
      was similar in Groups A and B, revealing two peaks: one early during infusion and
      a second one after the end of a 12-h cerulein infusion. Jun protein was found
      mainly in the acinar cells. In conclusion, (1) acinar cells in the rat pancreas
      respond to cerulein stimulation by increasing the expression of jun; (2) in vivo
      high doses of cerulein increase the jun mRNA and jun protein levels, whereas low
      doses raise only the protein levels; and (3) myc and fos are apparently
      uninfluenced by cerulein administration.

PMID- 9260202
TI  - The influence of transforming growth factor beta 1 on the expression of genes
      coding for matrix metalloproteinases and tissue inhibitors of metalloproteinases
      during regeneration from cerulein-induced pancreatitis.
AB  - Enhanced synthesis and deposition of extracellular matrix (ECM) components is a
      characteristic feature during regeneration from acute cerulein-induced
      pancreatitis in rats. Transforming growth factor beta 1 (TGF beta 1) has been
      suggested to be an important modulator of the ECM by interfering with a number of
      essential processes such as the synthesis of ECM components. To study the
      involvement of the ECM degrading proteases (matrix metalloproteinases; MMPs) and
      their specific inhibitors in the process of pancreatic regeneration, we examined
      the expression of these genes on the transcript level and the activation of the
      corresponding enzymes by use of zymographies. Pancreatic RNA and protein were
      extracted from rats sacrificed 1, 2, 3, 5, and 7 days after induction of cerulein
      pancreatitis. To investigate the influence of TGF beta on gene expression of ECM
      proteases and their specific inhibitors, we blocked the activity of TGF beta 1
      during regeneration from acute pancreatitis by use of neutralizing antibodies
      against TGF beta 1. Steady levels of 72-kD type IV collagenase (MMP-2),
      stromelysin (MMP-3), and tissue inhibitor of metalloproteinase 2 (TIMP-2) mRNA
      were significantly increased 2 days after induction of pancreatitis. MMP-9 and
      MMP-3 enzyme activity was elevated 12 h after induction of pancreatitis, whereas
      MMP-2 activity increased 12 h later. Inhibition of TGF beta 1 by neutralizing
      antibodies only reduced the amount of stromelysin transcripts throughout
      pancreatic regeneration. In summary, ECM degrading proteases, in particular
      stromelysin, appear to be involved in ECM remodeling during pancreatic
      regeneration. TGF beta 1 may be responsible for regulation of stromelysin
      transcription.

PMID- 9260203
TI  - Expression of Bcl-2 and PCNA in duct cells after pancreatic duct ligation in
      rats.
AB  - Obstruction of the pancreatic duct induces acinar cell deletion followed by duct
      proliferation and interstitial fibrosis. Apoptosis has been reported to be
      involved in the induction of acinar cell deletion after pancreatic duct ligation
      (PDL) in rats, however, the mechanism of pancreatic duct cell proliferation is
      still unknown. We hypothesized that Bcl-2 (antiapoptosis protein) and PCNA (cell
      cycle-related protein) could be involved in the mechanism of pancreatic duct cell
      proliferation after PDL. In PDL, rats, acinar cells decreased in number and
      disappeared completely after duct ligation and duct-lining cells increased in
      number and formed duct-tubular complexes. Immunohistochemical study showed that
      PCNA expression appeared in the ductules and centroacinar cells from early stages
      after duct ligation and that Bcl-2 expression in duct cells, which was faint in
      normal pancreas, increased significantly when acinar cells were diminishing.
      Western blotting demonstrated that Bcl-2 was detected as a single band at 26 kDa,
      and the intensity of Bcl-2 in PDL rats was approximately ninefold stronger than
      in normal pancreas. Expression of Bcl-2 and PCNA after pancreatic duct ligation
      may be related to the prevention of apoptosis and cell proliferation of
      pancreatic duct cells in rats.

PMID- 9260204
TI  - A comparison of two methods to measure amylase, lipase, trypsin, and chymotrypsin
      activity and the effect of freezing and thawing on enzyme activities in
      pancreatic juice.
AB  - An experiment was conducted to compare two methods, referred to as A and B, for
      measuring amylase, lipase, trypsin, and chymotrypsin activities in samples of
      pancreatic juice and to investigate the effect of freezing and thawing on enzyme
      activities. Three growing pigs were used in this study. A catheter was surgically
      inserted into the pancreatic duct and a simple T-cannula was placed in the
      duodenum to allow the return of collected pancreatic juice. Pancreatic juice was
      collected for a total of 24 h and 27 pooled 8-h samples were used in the
      analyses. Following collection and pooling, the samples were frozen at -80
      degrees C, due to the large number of samples and analyses, and stored for 2
      weeks. The samples were thawed and enzyme activities were determined with Method
      A. The samples were frozen again at -80 degrees C, stored for 2 weeks, and
      rethawed and enzyme activities were determined with Methods A and B. There was a
      direct relationship between Method A and Method B for measuring amylase, trypsin,
      and chymotrypsin activity (R2 = 0.95, 0.81, and 0.90, respectively). However, a
      poor relationship was observed between a titrimetric and a photometric method for
      determining lipase activity (R2 = 0.42). A second freezing, storage, and thawing
      did not affect (p > 0.3) the concentration of protein or amylase activity in
      pancreatic juice. However, the activities of chymotrypsin, trypsin, and,
      especially, lipase were decreased by 29.0% (p < 0.11), 40.4% (p < 0.01), and
      82.9% (p < 0.001), respectively. In conclusion, either Method A or Method B can
      be used to measure amylase, trypsin, and chymotrypsin activities in pancreatic
      juice but a titrimetric method should be used to determine lipase activity.
      Furthermore, if the activities of lipase, trypsin, and chymotrypsin are to be
      determined, the sample should only be frozen and thawed once. If amylase activity
      will be determined, the sample can be repeatedly frozen and thawed.

PMID- 9260205
TI  - Duodenal secretion and fecal excretion of pancreatic elastase-1 in healthy humans
      and patients with chronic pancreatitis.
AB  - Fecal elastase-1 is a candidate for a sensitive noninvasive test detecting
      chronic pancreatitis. This prospective study enrolled 10 healthy male controls
      and 23 patients referred for tube testing of pancreatic function. It was designed
      (a) to correlate duodenal outputs and fecal concentrations of elastase-1 with
      duodenal outputs of amylase, lipase, trypsin, and chymotrypsin in the fed state
      (duodenal perfusion of a mixed liquid meal at 2.5 kcal/min for 150 min), (b) to
      compare the diagnostic accuracy of fecal elastase-1 and fecal chymotrypsin, and
      (c) to characterize the cyclical pattern of postprandial pancreatic secretion in
      healthy subjects and patients with chronic pancreatitis. Based on their enzyme
      responses to duodenal meal perfusion and imaging procedures, 12 patients were
      classified as having normal pancreatic function and 11 patients as having chronic
      pancreatitis. Duodenal enzyme outputs of elastase-1 were markedly lowered in
      chronic pancreatitis (p < 0.0001) and correlated well with the outputs of the
      other four enzymes (r > 0.71, p < 0.00001). Fecal concentrations of elastase-1
      were also clearly reduced in chronic pancreatitis (p < 0.0001). Fecal
      chymotrypsin was less strongly associated with duodenal enzyme outputs (r = 0.33
      to r = 0.587), whereas fecal elastase-1 correlated more precisely with the
      duodenal outputs of all five enzymes (r = 0.637 to r = 0.830, p < 0.00001).
      Sensitivity and specificity in the detection of chronic pancreatitis amounted to
      0.64 and 0.95 for fecal elastase-1 and 0.27 and 0.95 for fecal chymotrypsin,
      respectively. In the postprandial state, peaks of enzyme secretion occurred at a
      frequency of about 1 peak/150 min. The amplitude but not the frequency of
      secretory peaks was markedly reduced in chronic pancreatitis (p < 0.01). We
      conclude that fecal elastase-1 clearly exceeds the sensitivity of fecal
      chymotrypsin in the diagnosis of chronic pancreatitis but does not reliably
      detect all cases with mild to moderate disease. The pattern of postprandial
      pancreatic secretion is cyclical, even with minimal secretory outputs in chronic
      pancreatitis.

PMID- 9260206
TI  - Mixed osteoclastic/pleomorphic-type giant cell tumor of the pancreas with ductal
      adenocarcinoma: histochemical and immunohistochemical study with review of the
      literature.
AB  - We described a rare form of giant cell tumor of the pancreas composed of mixed
      osteoclastic/pleomorphic-type giant cell tumor with ductal adenocarcinoma.
      Immunohistochemical study showed positive staining of cytokeratin and epithelial
      membrane antigen for pleomorphic-type giant cells and ductal adenocarcinoma but
      negative for osteoclastic-type giant cells. Vimentin stained positive in both
      types of giant cells but negative in adenocarcinoma. Osteoclastic-type giant
      cells were strongly positive for CD68 and tartarate-resistant acid phosphatase
      was present in these cells, suggesting the osteoclast-like character. CD68 was
      negative for both pleomorphic-type giant cells and ductal adenocarcinoma. From
      these findings, we consider that this tumor might be a carcinosarcoma-like
      neoplasm consisting of both an epithelial and a histiocytic-mesenchymal
      component.

PMID- 9260207
TI  - Bromhexine hydrochloride eliminates protein plugs and relieves attacks of
      pancreatitis.

PMID- 9260208
TI  - The Whipple pancreatoduodenectomy in the treatment of pancreatic lymphoma.

PMID- 9260209
TI  - Acute pancreatitis revealing diffuse infiltration of the pancreas by melanoma.

PMID- 9260210
TI  - Drug-associated pancreatitis: facts and fiction.

PMID- 9260211
TI  - Association between pronounced IgA response in RSV bronchiolitis and development
      of allergic sensitization.
AB  - Forty-five children who had been hospitalized with bronchiolitis caused by
      respiratory syncytial virus (RSV) at a mean age of 4 months, and 90 matched
      control children, were tested for occurrence of RSV antibodies at one year of
      age. Of the children who had suffered from bronchiolitis, forty had demonstrable
      IgG antibodies, whereas the remaining five only had IgA antibodies against RSV.
      In the control group, 42% were RSV seropositive. The anti-RSV IgA antibody titres
      tended to be higher in patients with bronchiolitis than in controls and a larger
      proportion of the seropositive children in the former than in the latter group
      had demonstrable IgG antibodies. These findings suggest that RSV infections
      causing bronchiolitis are more often associated with a strong antibody response
      than are mild cases of the infection. Follow-up of the children at 3 years of age
      showed that allergic sensitization and development of asthma had occurred much
      more frequently in children with past RSV bronchiolitis than in controls.
      Children with past RSV bronchiolitis who later developed allergic sensitization
      had elevated RSV IgA antibody titres at one year of age more frequently than
      children with past RSV-bronchiolitis, who were not sensitized (p = 0.015). No
      significant differences regarding IgG antibody titres were observed. Since IgA,
      similarly as IgE, antibody formation is strongly Th2 cell dependent, the results
      are compatible with other findings suggesting that RSV has an unusual propensity
      to activate the Th2 cell system. This may contribute to the pathological picture
      of bronchiolitis in small children and at the same time render the infected child
      predisposed for later development of allergic sensitization. RSV bronchiolitis
      may thus be an important risk factor for later development of atopic disease
      although it cannot be excluded that the bronchiolitis simply serves as a marker
      that predict later development of atopy.

PMID- 9260212
TI  - Early intervention for the prevention of atopic dermatitis.
AB  - Based on a lecture given to the European Society for Pediatric Allergy and
      Clinical Immunology. Diseases associated with atopy are increasing throughout the
      world. Individuals appear to have a genetic predisposition to atopy which is then
      provoked by environmental influences. Ingested or inhaled allergens provoke an
      antibody response and a state of sensitization. In many but not all sensitized
      individuals subsequent exposure to allergen will provoke a release of histamine
      and other mediators from sensitized mast cells and produce clinical signs of an
      allergic reaction in the target organ or throughout the body. At the present time
      one approach to the prevention or reduction of such reactions appears to be the
      identification of the high-risk infant and then preventing or limiting exposure
      to the potentially allergenic protein materials in the child's diet or immediate
      environment. This paper outlines the problems of identifying high-risk infants
      and comments on the success claimed in the intervention studies that have been
      undertaken. The possible hazards to mothers and infants of dietary exclusion are
      emphasized and the provision of appropriate medical and dietetic support are
      regarded as of paramount importance. Although more studies are needed, the Isle
      of Wight intervention programme offers hope to families at high-risk of atopy
      that the problem can be reduced for the next generation.

PMID- 9260213
TI  - Asthma induced by ice water ingestion in ethnic Chinese asthmatic children: a
      challenge.
AB  - The purpose of this study was to investigate the relationship between ice water
      ingestion and the induction of asthmatic symptoms and signs in ethnic Chinese
      asthmatic children. Sixty asthmatic children with a positive history of
      exacerbation of symptoms after drinking ice water were divided randomly into two
      groups: 34 children were instructed to drink 250 ml of 0-4 degrees C ice water
      within one minute, and 26 to drink 250 ml of 25 degrees C warm water. All of the
      asthmatic children were stable when studied. Twenty-three healthy children as
      controls were asked to drink 250 ml of 0-4 degrees C ice water. The three groups
      had forced expiratory volume in one second (FEV1) performed at baseline and at 5,
      15, 30, 60, and 90 minutes after challenge. After the spirometric test at 90
      minutes the patients of the two asthmatic groups received three puffs (0.6 mg) of
      hexoprenaline MDI and a further spirometric test was performed 5 min after the
      inhalation. Cough and wheeze were monitored throughout the course of the test.
      The mean FEV1 after challenge decreased significantly only in the ice-water
      asthmatic group (p = 0.004). Compared with the baseline data, the mean FEV1 at
      various periods after challenge was only significantly decreased at 60 min (p =
      0.035). After hexoprenaline inhalation the FEV1 significantly increased in the
      two asthmatic groups (p < 0.001). A significant difference in FEV1 change was
      noted among the three groups (p = 0.015). Nine cases (26%) from the ice water
      asthmatic group, three (12%) from the warm-water asthmatic group, and none of the
      ice-water normal control group showed a decrease of FEV1 greater than 15% (p =
      0.018). The greatest difference occurred between the two ice water groups. All
      six cases who developed symptoms after challenge, accompanied by a simultaneous
      decrease of FEV1 greater than 15%, belonged to the ice-water asthmatic group.
      Forty-seven percent of the ice-water asthmatic group and 4% each of the two other
      groups had cough and/or wheeze after challenge (p = 0.0002). IN CONCLUSION: Ice
      water ingestion may induce or exacerbate asthma in ethnic Chinese asthmatic
      children.

PMID- 9260214
TI  - Measles vaccine in egg allergic children: poor immunogenicity of the Edmoston
      Zagreb strain.
AB  - Despite the fact that a number of recent studies have shown that measles/
      mumps/rubella vaccine is safe for egg allergic children, many pediatricians are
      still concerned about immunization in egg allergic children. In Europe, a measles
      vaccine with the Edmoston-Zagreb strain (EZMV) grown in human fibroblast culture
      has been developed and recommended for children with egg allergy. However, some
      doubt arises on the efficacy of this strain due to its weak immunogenicity. The
      aim of this study was to investigate the immunogenicity of the EZMV in comparison
      to the measles vaccine with the Schwarz strain (SWMV) grown in a chick embryo
      fibroblast culture. Thirty-nine children affected by severe immediate
      manifestations due to IgE mediated egg allergy were enrolled. The children
      received at random the SWMV (Morupar, Sclavo) or the EZMV (Triviraten, Berna) in
      one 0.5 ml subcutaneous injection, and were checked for any immediate allergic
      reactions in the following 4 hours. Blood samples were taken for the detection of
      specific antibody response 5 months after the immunization. In SWMV seroconverted
      children (18/19) the geometric mean antibody titer was 3 times higher than that
      observed in EZMV seroconverted children (17/20) (p < 0.01). No allergic reactions
      occurred following the immunization with the two different vaccines. This data
      confirms the safety of SWMV in egg allergic children. In addition, the present
      study provides further data on the lower immunogenicity of the EZMV in comparison
      to the SWMV.

PMID- 9260215
TI  - Double-blind placebo-controlled study of sublingual immunotherapy with house dust
      mite extract (D.pt.) in children.
AB  - SAFETY and efficacy of sublingual (sublingual-swallow) immunotherapy (IT) with
      house dust mite extract were evaluated in 30 children (6-15 2/3 years of age)
      over the first 12 months of an ongoing study. The cumulative dose was 570
      micrograms Der p I (five times that administered with subcutaneous therapy).
      SAFETY: One patient on active treatment dropped out after 8 weeks because of a
      subjective feeling of severe weakness, questionably induced by the therapy. Five
      patients on active therapy and one patient on placebo reported minor local side
      effects. EFFICACY: Pulmonary symptoms were reduced after 12 months in actively
      treated asthmatics, but this was not consistent with the lack of improvement in
      bronchial reactivity, skin sensitivity and specific IgG and IgG4 against D.pt. in
      this group. In patients with rhinitis nasal sensitivity was reduced in the
      placebo group without concomitant improvement in the nasal symptom score.
      Specific IgE (D.pt. and D.f.) increased significantly more in the active
      treatment group after 3 and 12 months. We conclude that sublingual IT over 12
      months with the fivefold Der p 1 dose of subcutaneous IT was well tolerated, but
      there was no consistent clinical or immunological benefit compared to placebo.

PMID- 9260216
TI  - Scoring of atopic dermatitis by SCORAD using a training atlas by investigators
      from different disciplines. ETAC Study Group. Early Treatment of the Atopic
      Child.
AB  - The ETAC (Early Treatment of the Atopic Child) study, a multi-national double
      blind placebo-controlled randomized trials, has been in progress since 1994.
      Fifty-six centers in Europe and Canada participate in this study. A total of 817
      children with atopic dermatitis [AD] were recruited. The severity of AD was
      scored using the SCORAD (objective criteria). Ninety-eight investigators (mostly
      pediatricians) were trained by three members of the European Task Force on Atopic
      Dermatitis [ETFAD] to standardize their objective SCORAD scoring (system
      developed by the ETFAD). The experts selected photographs and prepared a training
      atlas. The percentages of photographs assessed by the 98 non-expert investigators
      below, within and above the range of evaluations by the three experts were
      calculated. Taking over and underscoring together, edema/papulation was the
      easiest intensity item to score (82% within the range by the experts). The global
      symptom score, as well as lichenification, edema/papulation, oozing and
      excoriation registered by physicians with dermatological experience were not
      statistically significantly different from those by other. Erythema was
      statistically significantly better scored by those with dermatological
      experience. The results of the Euclidean Distance method showed that the item
      excoriations gave the largest distance. Erythema and excoriations were scored
      better by dermatologically experienced physicians (t-test, p = 0.042 and p =
      0.063 respectively), but lichenification was better scored by non
      dermatologically experienced physicians (p = 0.013). The extent of surface area
      involved in the disease was calculated on 3 sets of photographs. Most evaluations
      by the 98 nonexpert investigators were within the range of the experts.
      Dermatologically experienced physicians scored significantly better than the
      others (t-test, p = 0.006). This training program is useful for standardizing the
      scoring in AD and indicates that SCORAD can be used by investigators from
      different disciplines.

PMID- 9260217
TI  - The prevalence of respiratory symptoms and asthma among school children in three
      different areas of Norway.
AB  - The role of exposure to ambient air pollution has been a topic of interest as a
      potential risk factor for respiratory symptoms and asthma. We expected that the
      prevalence rates would vary in Norway between the capital, Oslo, the mountainous
      area Hallingdal and the industrial area Odda. Surveys were conducted in school
      children, aged 6-16 years, in; Oslo (n = 2577), Hallingdal (n = 1177) and Odda (n
      = 831). The parent-reported prevalence of wheeze in past year was almost similar
      in Oslo (13.1 (95% CI 11.7-14.5)) and Upper Hallingdal (14.2 (13.1-15.3)), but
      lower in Odda (9.0 (7.0-11.0)). The findings for severe respiratory symptoms were
      almost equal. The age patterns within each area differed. The risk of wheeze ever
      (p < 0.001) and wheeze in past year (p = 0.04) decreased with increasing age in
      Odda, while there was an increase in the risk of exercise induced wheeze in Oslo
      (p = 0.02) and Hallingdal (p < 0.001). The lifetime prevalence of asthma was
      lowest in Odda (5.4 (3.8-7.0)) compared to Oslo (9.4 (8.2-10.6)) and Hallingdal
      (8.5 (6.8-10.2)). There was a positive association between physical activity and
      wheeze in past year. The results do not support the hypothesis that respiratory
      morbidity is more common in urban than rural areas, age and physical activity can
      influence the prevalence rates of respiratory symptoms in school children.

PMID- 9260218
TI  - Labial food challenge in children with food allergy.
AB  - The current increase in the prevalence of food allergies appears to have several
      causes including better screening, improved diagnosis and changes in both the
      techniques used by food manufacturers and eating habits. Labial food challenge
      (LFC)is simple, rapid to perform and is associated with only low risks of
      systemic reaction. It is thus an appealing alternative to the oral food challenge
      (OFC) for pediatric use. We report a series of 202 LFC performed over two years
      in 142 children with food allergy suspected from the case history, positive skin
      prick tests and specific serum IgE assays: 156 LFC were positive; and 46
      negative, followed by positive single-blind, placebo-controlled food challenges
      (SBPCFC). The foods provoking reactions were egg white (75 cases), peanut (60
      cases), mustard (23 cases), cow's milk (13 cases), cod (8 cases), kiwi fruit,
      shrimp (4 cases each), chicken, peanut oil (3 cases each), hazel nuts (2 cases),
      and snails, apple, fennel, garlic, chilli peppers, pepper, and duck (1 case
      each). LFC positivity was mostly (89.7% of cases) manifested as a labial edema
      with contiguous urticaria. There were systemic reactions in 4.5% of cases:
      generalized urticaria, hoarseness and rapid-onset and generalized eczema. The 46
      infants with negative LFC results had positive SBPCFC. The reactions were in 34
      cases generalized urticaria, 10 cases asthma attacks, 2 cases early and
      generalized eczema, and in one case general anaphylactic shock. The sensitivity
      of the LFC was 77%. The LFC was easy to perform with children. Positive results
      indicate the presence of food allergy, but negative results require further
      investigations preferably double-blind, placebo-controlled food challenge
      (DBPCFC).

PMID- 9260219
TI  - Eosinophil cationic protein in induced sputum as a marker of inflammation in
      asthmatic children.
AB  - We evaluated the usefulness of eosinophil cationic protein (ECP) in induced
      sputum and in serum as markers of asthmatic inflammation in children. We measured
      ECP in serum and in total induced sputum samples from 14 children (7-11 years)
      with newly detected asthma before and after treatment, and from ten healthy non
      atopic controls of the same age. The patients inhaled budesonide, 800
      micrograms/m2/day for the first month and 400 micrograms/ m2/day for the next 5
      months, both divided into two doses, and nedocromil, 4 mg three times daily for
      the following 6 months. In both sputum and serum, ECP levels were higher in the
      patients than in the controls, but the difference was more distinct in sputum.
      Significant clinical improvement during the treatment was accompanied by a
      decrease in sputum ECP, whereas serum ECP did not change. The results suggest
      that induced sputum is useful as a non invasive source material for evaluating
      asthmatic inflammation in children, total sputum ECP being more sensitive than
      serum ECP for diagnosing and monitoring asthma.

PMID- 9260220
TI  - Atopy and latex allergy in spina bifida: what's chicken, what's egg?

PMID- 9260221
TI  - Utilization of dental services by Iowa Medicaid-enrolled children younger than 6
      years old.
AB  - All Medicaid-enrolled children are eligible to receive dental care through the
      Early and Periodic Screening, Diagnostic and Treatment Program (EPSDT). As part
      of an evaluation of the effectiveness of the EPSDT program in Iowa, Medicaid
      enrollment and claims files from fiscal year (FY) 1994 were used to evaluate the
      utilization of dental services by Medicaid-enrolled children younger than age 6
      during FY 1994. During FY 1994, 23% of Medicaid-enrolled children younger than
      age 6 received at least one dental service while enrolled in the Medicaid
      program. The total Medicaid-allowed charges for all dental services provided to
      this population while enrolled in Medicaid during FY 1994 was $1.53 million (the
      amount Medicaid would pay for the service, prior to calculating any copayments or
      other insurance charges). Although the EPSDT program in Iowa requires a referral
      of all Medicaid-enrolled children to a dentist at 1 year of age, fewer than 4% of
      enrolled children in this age group received any dental services. The percent of
      enrolled children receiving a dental exam during FY 1994, by age, was as follows:
      younger than 1 year, 0.2%; age 1, 3%; age 2, 10%; age 3, 27%; age 4, 46%; age 5,
      54%. Utilization rates of dental services by Medicaid-enrolled children in Iowa
      fall far short of federal regulations, which currently require that 80% of
      enrollees receive EPSDT screenings, referrals, and treatment by age 3.

PMID- 9260222
TI  - Effect of Medicaid reimbursement rates on children's access to dental care.

PMID- 9260223
TI  - Factors that affect career choices of pediatric dentistry advanced education
      students.
AB  - A questionnaire addressing factors that affect career choices by pediatric
      dentistry advanced education students was mailed to 52 training programs. Two
      hundred and thirty-two completed surveys from 45 responding programs were
      returned. The responses were analyzed for women and men and citizens and
      noncitizens. Concern for spouse career opportunities affected women's personal
      career decisions significantly more (P < 0.05) than it did for men. Women rated
      previous federal/military experience significantly less (P < 0.05) influential on
      their career choice than did men. Geographic preference when making career
      decisions was significantly more (P < 0.001) important to citizens than it was
      for noncitizens. Noncitizens assigned significantly higher (P < 0.001) ratings to
      an interest in teaching and research than did citizens. A preference for
      practicing with a parent or relative and previous federal/military experience
      affected career choices by noncitizens significantly more (P < 0.05) than they
      did citizens. This study suggests that numerous career-influencing factors in
      pediatric dentistry are perceived differently by women and men, and citizens and
      noncitizens.

PMID- 9260224
TI  - Bonded orthodontic brackets demonstrate similar retention on microabraded and
      nonmicroabraded tooth surfaces.

PMID- 9260225
TI  - Changes in the dentition secondary to palatal crib therapy in digit-suckers: a
      preliminary study.
AB  - This study investigated the effect of the palatal crib appliance used in the
      correction of open bite malocclusions secondary to fingersucking. Twelve
      experimental and 12 control subjects were studied for an average of 3.9 months.
      The sample consisted of patients who were both growing and not growing. Study
      models taken before and after the study period were analyzed for changes in the
      following dimensions: overbite, overjet, arch perimeter, arch length, and incisor
      angulation. Data were analyzed with student t-tests to determine statistical
      significance. Partial or complete closure of the open bite was achieved averaging
      3.7 mm +/- 1.9 mm during the observation period in the experimental group treated
      with palatal crib therapy. In contrast, the control group displayed a mean bite
      opening of 0.4 mm +/- 0.8. These values were statistically significant at the P <
      0.001 level. Open bite decreased as incisor angulation (P < 0.02), arch length (P
      < 0.05), and arch perimeter (P < 0.01) decreased. Overjet changes were minimal
      and statistically insignificant.

PMID- 9260226
TI  - Ferric sulfate versus dilute formocresol in pulpotomized primary molars: long
      term follow up.
AB  - The aim of this study was to compare the effect of ferric sulfate (FS) to that of
      dilute formocresol (DFC) as pulp dressing agents in pulpotomized primary molars.
      Ninety-six primary molars in 72 children were treated by a conventional pulpotomy
      technique. Fifty-eight teeth were treated by a FS solution for 15 sec, rinsed,
      and covered by zinc oxide-eugenol paste (ZOE). In another 38 teeth, a cotton
      pellet moistened with 20% DFC was placed for 5 min, removed, and the pulp stumps
      were covered by ZOE paste. The teeth of both groups were sealed by a second layer
      of intermediate restorative material (IRM) and restored with a stainless steel
      crown. This is a report of the clinical and radiographic examination of 55 teeth
      dressed with FS and 37 teeth fixed with DFC, that have been treated 6 to 34
      months previously (mean 20.5 months). Four teeth were excluded from the study due
      to failure of the patient to present for recall. Success rates of 92.7% for the
      FS, and of 83.8% for the DFC were not significantly different. Four teeth (7.2%)
      of the FS group and two (5.4%) of the DFC group presented internal resorption.
      Inter-radicular radiolucencies were observed in two teeth of the FS group and
      three teeth of the DFC group. The latter also presented periapical lesions.
      Success rates of both groups were similar to those of previous studies utilizing
      the traditional Buckley's formocresol.

PMID- 9260227
TI  - The basis for clinicians' caries risk grouping in children.
AB  - Despite the growing emphasis on targeting care to high-risk groups, little is
      known about the factors used by clinicians to designate risk. This study
      investigates the degree to which factors measured in a typical dental health
      survey are used by clinicians in assigning children to dental disease risk
      groups. A random sample of 9690 children aged 5-15 years was selected from the
      South Australian School Dental Service. Dentists or dental therapists judged each
      child as low-, medium-, or high-risk for dental disease. Clinicians recorded
      caries experience (DMFS/dmfs), and children's parents completed a questionnaire
      on dental behaviors and socioeconomic status (SES). Two binary logistic models
      were fitted using the risk grouping as the outcome variable, one comparing low-
      with moderate-risk and the other comparing moderate- with high-risk. Sixty
      percent of children were judged as moderate-risk, 27% as low-risk, and only 13%
      as high-risk. In the logistic models, proximal DMFS/dmfs were stronger predictors
      of assignment to the higher-risk groups than were factors indicating past
      occlusal caries, while factors describing caries on buccal or lingual surfaces
      appeared unimportant. Untreated lesions on permanent and primary teeth were among
      the strongest predictors of assignment to the higher-risk groups. Other
      significant factors (P < 0.05) were: exposure to professionally applied fluoride
      and sealants, country of birth, frequency of toothbrushing, and exposure to
      fluoridated water. No SES factors reached significance. The models explained
      nearly one-half the variation in the risk predictions. Clinical markers of past
      caries experience explained the greatest variation in the judgments, showing that
      clinicians base their risk predictions largely on children's past disease. The
      three types of surfaces contribute unevenly to the judgments and unrestored
      caries was the largest contributor to the decision.

PMID- 9260228
TI  - The effect of some Mexican citric acid snacks on in vitro tooth enamel erosion.

PMID- 9260229
TI  - A child has died in your office.

PMID- 9260230
TI  - Milk and egg albumen are superior to human saliva in preserving human skin
      fibroblasts.
AB  - The purpose of this in vitro study was to compare egg albumen, whole bovine milk,
      human saliva, and tissue culture medium (MEM) for effect on the viability of
      human skin fibroblasts and their osmolalities. Confluent monolayers of
      fibroblasts were grown. Growth medium was poured off and dishes were divided into
      five groups, 15 dishes each of: 1) chick egg albumen; 2) fresh whole milk; 3)
      human saliva; 4) tissue culture medium; and 5) bench-dried storage without any
      media. After 15, 45, and 90 min the average number of vital cells was measured
      using the trypan blue dye exclusion test. Tissue culture medium represented the
      best preservation media for human skin fibroblast cells (92.8% at 45 min, 87.6%
      at 90 min). No significant differences were observed between milk and albumen,
      with a majority of the cells surviving after 90 min (67.6% and 70.2%,
      respectively). Human saliva, due to its hypotonicity, markedly swelled the cells,
      causing decreased cell viability (27.4% at 90 min). Bench-dried cells, as
      expected, showed no viable cells as early as 15 min. The osmolality of the MEM,
      milk and egg albumen ranged between 251-298 mOsm/kg, whereas the saliva was
      hypotonic, with an osmolality of 73 mOsm/kg.

PMID- 9260231
TI  - Oral manifestations in Rett syndrome: a study of 17 cases.
AB  - Seventeen patients with a mean age of 7.33 (range 2.7-12.7) years with Rett
      syndrome (a progressive neurological disorder that occurs mainly in females) were
      evaluated for oral manifestations and habits. The most frequent habits were
      digit/hand sucking and/or biting (17/17), bruxism (14/17), mouth breathing
      (7/17), drooling (5/17), and tongue thrusting (5/17). Gingivitis (13/17) was the
      most common alteration of soft tissues. Only 2.7% of tooth surfaces were decayed.
      Nonphysiological dental attrition was present in 71% (12/17) of the children.
      Palatal shelving could be observed in 53% (9/17) of the children, probably
      related to the digit/hand sucking and/or biting habits. A high prevalence of
      anterior open bite (9/17) was observed. No patients exhibited anomalies of tooth
      number, size, form, structure, or eruption.

PMID- 9260232
TI  - Risk factors for chronic rejection in pediatric renal transplant recipients--a
      single-center experience.
AB  - Chronic rejection (CR) is the most common cause of graft loss beyond the 1st
      posttransplant year. The aim of this analysis was to identify the risk factors
      for the development of CR in pediatric renal transplant recipients. Between June
      1984 and March 1994, 217 renal transplants were performed in children at our
      center. Immunosuppression included prednisone, azathioprine, cyclosporine (CsA),
      and prophylactic antibody. Using multivariate analysis, we studied the impact of
      the following variables on the development of biopsy-proven CR: age at transplant
      (< or = 5 years, > 5 years), gender, race, transplant number (primary,
      retransplant), donor source (cadaver, living donor), donor age (< 20 years, 20-49
      years, > 49 years), number of ABDR mismatches (0, 1-2, 3-4, 5-6), number of DR
      mismatches (0, 1, 2), percentage peak panel reactive antibody (PRA) (< or = 50%,
      > 50%), percentage PRA at transplantation (< or = 50%, > 50%), dialysis
      pretransplant, preservation time > 24 h, acute tubular necrosis requiring
      dialysis, initial CsA dosage (< or = 5 mg/kg per day, > 5 mg/kg per day), CsA
      dosage at 1 year posttransplant (< or = 5 mg/kg per day, > 5 mg/kg per day),
      acute rejection (AR), number of AR episodes (ARE) (1, > 1), timing of AR (< or =
      6 months, > 6 months), reversibility of AR (complete, partial), and infection
      [cytomegalovirus (CMV), non-CMV viral, bacterial]. Risk factors for the
      development of CR in pediatric renal transplant recipients were: AR (P < 0.0001,
      odds ratio 19.4), multiple ARE (> 1 vs. 1) (P < 0.0001, odds ratio 30.1), and
      high percentage peak PRA (> 50%) (P < 0.03, odds ratio 3.6).

PMID- 9260233
TI  - Complications by age in primary pediatric renal transplant recipients.
AB  - We asked whether pediatric renal transplant recipients, subgrouped by age,
      differed in the percentage and number of hospital readmissions and in the
      incidence of infectious complications post transplant. Between 1 August 1985 and
      31 October 1993, a total of 164 patients < 18 years of age underwent primary
      transplants, with cyclosporine-based immunosuppression, at the University of
      Minnesota. The percentage of readmissions (P = NS), the mean number of
      readmissions (P = NS), and the length of hospital stay during readmissions (P =
      NS) did not differ significantly among age groups. The overall incidence of acute
      rejection was greater in those > or = 2 years than those < 2 years (P = 0.002),
      and in living donor recipients > or = 2 years versus those < 2 years (P = 0.02).
      The incidence of bacterial infection (< 2 years, 87%; 2-5 years, 72%; 6-12 years,
      51%; 13-17 years, 40%) was greater in younger recipients (P = 0.0001). The most
      common bacterial infection in recipients < or = 5 years was Clostridium difficile
      associated diarrhea; in those > 5 years, urinary tract infection. The overall
      incidence of viral infection did not differ among groups (P = NS). The most
      common viral infection in recipients < or = 5 years was varicella and those > 5
      years, cytomegalovirus infection. Risk factors for infection in the first 6
      months post transplant included age < 2 years and Solu-Medrol treatment for acute
      rejection. In conclusion, young recipients < 2 years of age at the time of
      transplant are at a higher risk for bacterial infection post transplant.

PMID- 9260234
TI  - Charge and size selectivity of proteinuria in children with idiopathic nephrotic
      syndrome.
AB  - Experimental studies have pointed to charge selectivity as an important
      determinant of glomerular permeability to macromolecules. Loss of glomerular
      basement membrane (GBM) polyanion has been proposed as a cause of the selective
      proteinuria in minimal change nephrotic syndrome (MCNS). However, the presence of
      less-anionic albumin in urine than plasma from MCNS and focal and segmental
      glomerulosclerosis (FSGS) patients has been interpreted both as evidence for
      partial maintenance of charge selectivity and for involvement of other pathogenic
      mechanisms. The exact role of charge selectivity in the pathogenesis of nephrotic
      proteinuria remains controversial. We have examined the clearance of endogenous
      proteins of differing size and charge in children with idiopathic nephrotic
      syndrome (NS). Chromatofocusing was used to determine the isoelectric points
      (pIs) of albumins in paired plasma and urine samples from patients with FSGS (n =
      6) and MCNS (n = 6). Charge selectivity was assessed by comparing the pIs of the
      fractions with the highest albumin concentration (model pI) in plasma and urine.
      The difference between the modal pIs was defined as the delta modal pI. Charge
      selectivity was also assessed from the albumin/transferrin and IgG4/IgG1
      clearance ratios; size selectivity from the IgG1/albumin and IgG1/transferrin as
      well as the IgG4/albumin and IgG4/transferrin clearances. In children with FSGS,
      the mean (+/-SD) delta modal pI was -0.05 +/- 0.16, and in MCNS -0.05 +/- 0.11.
      Neither value differed significantly from zero. The albumin/transferrin clearance
      ratio showed no significant difference between FSGS and MCNS, but the IgG4/IgG1
      clearance ratio was significantly higher in MCNS (P < 0.05). Size selectivity was
      significantly reduced in FSGS compared with MCNS (for IgG1/transferrin P < 0.01
      and for IgG1/albumin P < 0.05). For IgG4/transferrin and IgG4/albumin, P was <
      0.05. In conclusion, there was no evidence for residual charge selectivity in
      idiopathic NS associated with either MCNS or FSGS during nephrotic-range
      proteinuria. There was a significant loss of GBM size selectivity in children
      with FSGS with heavy proteinuria compared with children with MCNS with heavy
      proteinuria.

PMID- 9260235
TI  - Salivary excretion of endogenous proteins in nephrotic syndrome in children.
AB  - Size and charge selectivity of capillary permeability in the salivary glands of
      nephrotic children were investigated by measuring salivary excretion of
      endogenous plasma proteins of different size and charge. We examined 10 children
      with steroid-sensitive nephrotic syndrome (SSNS) in relapse and subsequent
      remission, 11 with steroid-resistant nephrotic syndrome, and 11 healthy children
      (controls). Albumin [mol. wt. 66 kilodaltons (kDa), isoelectric point (pI) 4.9]
      was measured by radio-immunoassay, transferrin (mol. wt. 77 kDa, pI 5.9) and
      immunoglobulins IgG1 (mol. wt. 150 kDa, pI 7-9) and IgG4 (mol. wt. 150 kDa, pI <
      6) by enzyme-linked immunoabsorbent assay. In saliva, no significant differences
      were found between the four groups of children for any of the four proteins.
      Also, the saliva/plasma ratios of the four proteins were not different among the
      four groups. From these data, we conclude that in subjects with SSNS in relapse,
      neither size nor charge selectivity of salivary gland capillary permeability are
      affected.

PMID- 9260236
TI  - Levamisole therapy in corticosteroid-dependent nephrotic syndrome.
AB  - The effect of prolonged treatment with levamisole was examined in 43 patients (30
      boys) with steroid-dependent nephrotic syndrome (SDNS). The mean age at
      institution of treatment was 4.0 +/- 2.0 years. Fourteen patients had previously
      received cyclophosphamide with an ensuing remission of 8.5 +/- 10 months.
      Following induction of remission with prednisolone, levamisole was administered
      at a dose of 2.5 mg/kg body weight on alternate days. Prednisolone was tapered by
      2.5-5 mg every 4 weeks to 0.5 mg/kg on alternate days. The duration of levamisole
      therapy ranged from 6 to 31 months (mean 17.4 +/- 8.4 months); 15 patients
      received levamisole for more than 18 months and 10 for more than 24 months.
      Prednisolone was discontinued in 18 patients after a mean duration of 11.7 +/-
      7.1 months, whereas in 21 patients its dose was reduced to 0.2-0.4 mg/kg on
      alternate days. The mean relapse rate prior to levamisole therapy was 3.0 +/- 1.5
      relapses/year, which reduced to 0.9 +/- 0.7 relapses/year during levamisole
      treatment (P < 0.001). A comparison of the response in 14 patients who had
      previously received cyclophosphamide with the other 29 patients did not show any
      significant difference. There were no side effects of levamisole therapy. Our
      findings suggest that prolonged treatment with levamisole is beneficial and safe
      in SDNS, with a marked steroid-sparing effect. A significant proportion of these
      patients can be kept in remission on levamisole alone.

PMID- 9260237
TI  - A controlled study of deflazacort in the treatment of idiopathic nephrotic
      syndrome.
AB  - Forty patients with steroid-dependent idiopathic nephrotic syndrome (INS), a mean
      follow-up of 5.5 years, and a mean number of relapses of ten were blindly
      assigned to either deflazacort (DFZ) (n = 20) or prednisone (PDN) (n = 20)
      according to a ratio of equivalence of DFZ/ PDN = 0.8. This treatment was given
      for 1 year. The number of relapses was significantly lower in patients receiving
      DFZ. After 1 year, 12 remained in remission with DFZ compared with 2 with PDN.
      Growth velocity was not different in the two groups. Bone mineral content,
      assessed by quantitative computed tomography of L1 L2 vertebrae, decreased after
      1 year by 6% in the DFZ group versus 12% in the PDN group (NS). The mean body
      weight increase of +3.9 +/- 4.1 kg in the PDN group was higher than that of the
      DFZ group, +1.7 +/- 2.8 kg (P = 0.06). Cushingoid symptoms tended to be less
      after 12 months in the DFZ group. In conclusion, this study shows that DFZ was
      more effective than PDN in limiting relapses in steroid-dependent INS, and that
      cushingoid symptoms, weight gain, and decrease in bone mineral content tended to
      be less marked with this drug than with PDN.

PMID- 9260238
TI  - Intensive pulse therapies for focal glomerulosclerosis in South African children.
AB  - Seven children with steroid-resistant focal segmental glomerulosclerosis (SR-FGS)
      were placed on a therapeutic protocol of methylprednisolone (MP), oral prednisone
      (pred) and oral cyclophosphamide (CYC) given over 16 months (regimen A). Another
      5 children with SR-FGS were treated with a shorter course of intravenous CYC
      (monthly doses over 6 months), intravenous MP (3 consecutive daily doses) and
      oral pred 2 mg/kg (alternate days) (regimen B). With regimen A, 1 child had a
      short remission, and in the others, oedema subsided, the urine protein/
      creatinine ratio decreased, haematuria disappeared and the estimated glomerular
      filtration rate (GFR) increased. The observation period was 21-42 months and the
      drugs were well tolerated. With regimen B, 2 patients went into complete
      remission, 1 had partial remission, 1 failed to respond and another died because
      of severe concurrent infections. In the responding children, oedema cleared, the
      urine protein/ creatinine ratio decreased, haematuria disappeared and the GFR
      rose. The follow-up was between 3 and 34 months. Minor side effects were alopecia
      and transient hypertension. Both regimens improved the quality of life of most
      children. Compared with regimen A, regimen B is six times less costly with a
      quarter of the number of hospital visits. These observations may be of value in
      designing appropriate multicentre controlled trials, which have been advocated
      recently, for the rational and optimum management of SR-FGS.

PMID- 9260239
TI  - Nephrotic syndrome in South African children: changing perspectives over 20
      years.
AB  - We review our 20-year experience of 636 children with nephrotic syndrome (NS) in
      Durban, South Africa; 306 (48.2%) were blacks, 307 (48.2%) Indians and 23 (3.6%)
      were a mixed group (coloured); 91 (14.3%) could not be categorised and were
      excluded from the analysis. In Indian children, 134 of 286 (46.8%) had biopsy
      proven minimal change NS (MCNS) and 94.8% of these were steroid sensitive (SS);
      60 (21%) had SSNS but without renal biopsy; 59 (20.6%) had focal segmental
      glomerulosclerosis (FSGS), with only 4.4% of these being SS. In blacks,
      membranous nephropathy accounted for 40% of cases; 86.2% were associated with
      hepatitis B virus antigens. Typical SSNS continues to be uncommon among blacks.
      Only 14.4% had either biopsy-proven SS-MCNS or SSNS; 32 had MCNS lesions on
      biopsy, but 18 were steroid resistant (SR); 67 of 236 (28.4%) had FSGS, all of
      whom were SR. Among coloured patients, 5 of 23 (21.7%) had biopsy-proven SS-MCNS
      and or unbiopsied SSNS; 10 (43.5%) had FSGS and 6 of 23 (26.1%) had membranous
      nephropathy. Proliferative lesions were present in only 2 of 23 (8.6%) coloured
      patients and was uncommon in all population groups. Overall mortality was 3.1%.
      In brief, this is the largest reported series of NS among children in Africa and
      shows a typical pattern in Indians, an unusual pattern of histological types in
      blacks and an intermediate picture in coloureds.

PMID- 9260240
TI  - Increased recognition of IgA nephropathy in African-American children.
AB  - Based upon the percentage of cases of IgA nephropathy (IgAN) in biopsy series, a
      lower prevalence has been assumed for African-Americans compared with Americans
      of European descent. This may be due to a racial difference in the basic
      underlying pathology of IgAN or to racial differences in patterns of referral and
      biopsy selection practices. Over the past decade (1985-1994), we have found
      similar incidences of IgAN in Caucasian and African-American children from Shelby
      County, Tennessee. The incidence was 3.0 cases per million per year for Caucasian
      and 5.7 cases per million per year for African-American children. IgAN may be
      more common in African-American children than previously appreciated. Population
      based incidence studies will be necessary to determine whether or not our
      experience has become a more widespread phenomenon.

PMID- 9260241
TI  - Epidemiology of chronic renal failure in children: a report from Sweden 1986
      1994. Swedish Pediatric Nephrology Association.
AB  - In a national survey, chronic renal failure (CRF) in Swedish children was studied
      during the period 1986-1994; 118 children (72 boys, 46 girls) with CRF, defined
      as a glomerular filtration rate below 30 ml/min per 1.73 m2 body surface area,
      were identified. The median annual incidence of CRF was 7.7 and that of terminal
      renal failure (TRF) 6.4 per million children. The prevalence of preterminal renal
      failure decreased from 29 to 21 per million children over the study period, while
      the prevalence of TRF increased from 17.8 in 1986 to 38 per million children in
      1994. The increase in TRF prevalence was due to a lower incidence of deaths due
      to uremia and a slightly increased incidence of TRF compared with an earlier
      study period, 1978-1985. The results point to a more active treatment of uremia
      in Sweden now than during the period 1978-1985. The congenital causes of CRF
      (renal malformations, obstructive conditions, and hereditary disorders) accounted
      for 67.5% of all cases, which is high compared with data from other countries. No
      child with non-obstructive pyelonephritis as a cause of CRF was identified. Age
      at detection of CRF and time from detection of CRF to TRF were studied. As a high
      proportion of children, 42%, reached 16 years of age without entering TRF, the
      value of presenting time from CRF to TRF for the remaining individuals is
      questionable. There were only minor differences in primary renal disease, age at
      presentation, and time from CRF to TRF when the study results were compared with
      those from 1978-1985.

PMID- 9260242
TI  - Immunization practices in children with renal disease: a report of the North
      American Pediatric Renal Transplant Cooperative Study.
AB  - To determine the current immunization recommendations of practicing pediatric
      nephrologists, a questionnaire was sent to the members of the North American
      Pediatric Renal Transplant Cooperative Society. Sixty-two percent of the centers
      responded. The results of the survey suggest that although consensus for
      approaching immunization does exist, recommendations do vary from center to
      center. Virtually all centers recommend standard vaccines [DTP, oral poliovirus
      (OPV), hepatitis B (Hep B), and Haemophilus influenzae B (Hib)] for their renal
      insufficiency and dialysis patients. Despite the fact that they are not
      infectious, standard killed vaccines (DTP, Hep B, Hib) are recommended less
      frequently for transplanted patients (86%) than their renal insufficiency (98%)
      and dialysis (near 100%) counterparts. Additionally, OPV and
      measles/mumps/rubella (MMR), both live viral vaccines, are rarely recommended
      post transplant. Almost 90% of centers recommend the use of influenza vaccine,
      while only 60% of centers recommend pneumococcal vaccine for children with renal
      disease. Over 70% of centers recommend the newly licensed varicella vaccine for
      patients on dialysis and those with renal insufficiency. Between 5% and 12% of
      centers recommend live viral vaccines, including OPV, MMR, and varicella vaccine,
      for immunosuppressed patients post renal transplant.

PMID- 9260243
TI  - Acquired renal cystic disease in children and young adults on maintenance
      dialysis.
AB  - Acquired renal cystic disease (ARCD) is a well-known complication of end-stage
      renal disease (ESRD). We studied 24 patients, aged 8-27 years (mean 19.8 +/- 5.3
      years), on chronic maintenance dialysis in our service. The duration of dialysis
      ranged between 13 and 192 months (mean 77.8 +/- 44.3 months). High-resolution
      ultrasonography revealed ARCD in 11 (45.8%) patients. No cysts were seen in 7
      (29.1%) patients and solitary cysts in one or both kidneys were seen in 6 (25%)
      patients. Renal malignancy was diagnosed in 2 patients. One, 15 years old, had
      renal cell carcinoma after being on dialysis for 6 years. She did well after
      bilateral nephrectomy, left salpingo-oophorectomy, and regional lymphadenectomy.
      The second patient, 23 years old, had been on dialysis for 16 years when she
      developed renal oncocytoma. She died of congestive cardiomyopathy 6 months later.
      We conclude that ARCD is common in children and young adults with ESRD.
      Neoplastic transformation, although rare, is a potential complication. Annual
      follow-up with ultrasonography with selective use of computed tomography or
      magnetic resonance imaging is advised.

PMID- 9260244
TI  - Papilledema in 15 renally compromised patients treated with growth hormone.
AB  - Intracranial hypertension with papilledema has been reported in renal patients,
      but a survey of the literature suggests that the incidence rate is low. We
      present reports of 15 of approximately 1,670 patients with renal disorders, who
      were treated with growth hormone for impaired growth and subsequently developed
      symptoms and/or signs of intracranial hypertension. The male:female ratio was
      6.5:1, and the median age was 12 years. The median duration of growth hormone
      treatment before onset of symptoms or signs was 13 weeks. All but 2 patients were
      symptomatic. In the patients in whom growth hormone therapy is known to have been
      discontinued, the symptoms and signs of intracranial hypertension abated. At
      least 4 of these patients experienced a recurrence when re-exposed to growth
      hormone. Many of the affected patients presented with predisposing conditions,
      but growth hormone appears to have been the precipitating factor. Prospective
      funduscopic evaluation may be warranted in patients with renal disorders who are
      receiving growth hormone.

PMID- 9260245
TI  - Variation in the diagnosis of vesicoureteric reflux using micturating
      cystourethrography.
AB  - Variability in the interpretation of micturating cystourethrography by paediatric
      radiologists for the diagnosis of vesicoureteric reflux in children was
      evaluated. All 265 micturating cystourethrograms (MCUs) that were available from
      304 consecutive children aged 0.5-61 months-who were investigated after their
      first urine infection between 1993 and 1995 as part of a prospective cohort study
      were selected for interpretation. Three experienced paediatric radiologists from
      the same department independently interpreted the MCUs according to the grading
      system of the International Reflux Study in Children, from grades 0 to V, with
      the presence of intrarenal reflux also noted. Apart from being informed that
      urine infection was the indication for the MCU, no other clinical information was
      given to the radiologists. The indices of variability used were the percentage of
      agreement and the kappa statistic, expressed as a percentage. Both measures were
      weighted with integers representing the number of categories from perfect
      agreement. Disagreement was analysed for children and kidneys. For the diagnosis
      of vesicoureteric reflux in individual patients, including grade, the percentage
      of agreement was 96%-97% (kappa 90%-91%) and the weighted percentage of agreement
      was 96%-98% (weighted kappa 93%-94%). The same high level of agreement was
      present for individual kidneys, with a percentage of agreement of 97%-98% (kappa
      89%-92%) and a weighted percentage of agreement of 98%-99% (kappa 94%-95%). There
      was near perfect agreement in the interpretation of radiological micturating
      cystourethrography among three experienced paediatric radiologists for the
      diagnosis and grade of vesicoureteric reflux. Any variations in the medical care
      of children suspected of having vesicoureteric reflux are not explained by
      differences in the reporting of this diagnostic test.

PMID- 9260246
TI  - The uretero-vesical jet as a functional diagnostic tool in childhood
      hydronephrosis.
AB  - Childhood hydronephrosis (HN) is accurately detected by ultrasound (US), but its
      functional work-up remains a domain of scintigraphy, the Whitaker-test, and
      clinical follow-up. We utilized color doppler US (CD-Jet) of uretero-vesical jets
      (UVJ) to visualize the post-obstructive ureteral flow in childhood HN. A total of
      177 standardized CD-Jet were performed in 132 children aged 1 day to 14.9 years.
      Sixty-nine investigations in 43 patients with unilateral HN were compared with a
      standardized technetium 99m-mercaptotriacetylglycine nephrogram; in 10 infants
      both procedures were performed consecutively on the same day. UVJ were visible in
      96% of all investigations. Ureteral obstruction resulted in absence of UVJ in 85%
      of examinations; in the remaining 15% the jet frequency was less than 10%
      observed in the contralateral control. Results are highly significant in both
      uretero-pelvic (P < 0.00007) and uretero-vesical lesions (P < 0.00005, Wilcoxon
      test) and are reproducible in sequential investigations. In nonobstructive distal
      HN the jet frequency averaged 70% of the unaffected side (P < 0.05). In proximal
      lesions it is equal. Jet evaluation in reflux nephropathy did not differ from
      controls. Compared with scintigraphy, CD-US identifies obstruction with a
      specificity of 94.2% and sensitivity of 94.8%. CD-US of UVJ therefore may serve
      as a reliable screening parameter in unilateral childhood HN.

PMID- 9260247
TI  - Percutaneous angioplasty of arteriovenous (Brescia-Cimino) fistulae in children.
AB  - The development of a stenosis in a Brescia-Cimino fistula is a major clinical
      problem that threatens vascular access for dialysis. We reviewed the case notes
      of 46 children undergoing hemodialysis via Brescia-Cimino fistulae. Ten children
      (mean age 12.5 years) developed 14 stenoses located in the venous (10),
      anastomotic (3), or arterial (1) part of the fistula. Three (1 arterial and 2
      anastomotic stenoses) of the 14 stenoses were treated surgically; the remaining
      11 (10 venous and 1 anastomotic stenoses) were treated by angioplasty. Seventeen
      angioplasty procedures were performed by the percutaneous venous route under
      local anesthesia. Mean follow-up was 24 months. Restenosis within 6 months
      occurred in 5 patients, predominantly those who had angioplasty with low balloon
      inflation pressures; 1 was treated surgically; 4 underwent repeat angioplasty
      using higher balloon inflation pressures (3 patients) or a bigger balloon (1
      patient). None subsequently developed restenosis. Angioplasty can be safely used
      to treat stenosis of arteriovenous fistulae, with a high initial (60% freedom
      from restenosis at 6 months) success rate. In summary, balloon angioplasty,
      repeated if necessary, is a safe and effective treatment for the majority of
      stenoses occurring in Brescia-Cimino fistulae. Restenosis can be safely treated
      by further angioplasty, which is associated with a high rate of ultimate clinical
      success.

PMID- 9260248
TI  - Renal functional reserve after acute poststreptococcal glomerulonephritis.
AB  - We evaluated renal functional reserve (RFR) in 36 patients aged 5-21 years, who
      had recovered from an acute episode of poststreptococcal glomerulonephritis
      (PSGN) 1-16 years previously, without apparent sequelae, as evidenced by normal
      serum creatinine, blood pressure, and urinary sediment. The control group
      consisted of 12 children aged 2-12 years with recurrent urinary tract infections
      or nocturnal enuresis, without active infection or anatomical anomalies. The
      basal creatinine clearance was similar in the PSGN and control groups: 140.0 +/-
      27.4 ml/ min per 1.73 m2 and 142.9 +/- 15.5 ml/min per 1.73 m2, respectively. The
      RFR in the PSGN group was significantly reduced compared with that of the control
      group: 18.6 +/- 12.9 ml/min per 1.73 m2 and 41.1 +/- 25.3 ml/min per 1.73 m2,
      respectively (P < 0.02). In 7 PSGN patients (19.4%), no RFR was found. In 69% of
      patients who had recovered from PSGN more than 10 years before the protein
      loading tests, a significantly reduced RFR (less than 10% of baseline) was found.
      The same degree of reduction in RFR was found in only 26% of patients who had
      suffered from PSGN less than 10 years ago.

PMID- 9260249
TI  - Complement activation in Henoch-Schonlein purpura.
AB  - The pathogenetic mechanism underlying Henoch-Schonlein purpura (HSP) is poorly
      understood. Complement activation has been thought to have a role, but despite
      the demonstration of complement components in skin and renal biopsy material,
      serological evidence of complement activation is not convincing. We have assessed
      complement activation in 64 children with acute HSP. We used an enzyme-linked
      immunosorbent assay to measure plasma levels of three multimolecular complement
      activation protein (CAP) complexes: C1r:C1s:C1-inhibitor, C3bP and C5b-9. We
      found no significant difference between the levels of CAPs in children with acute
      HSP and a control group of children. This study does not support a role for
      complement activation in the pathogenesis of HSP.

PMID- 9260250
TI  - Urinary N-acetyl-beta-D-glucosaminidase activity in rabbits with experimental
      hypercalciuria.
AB  - Routinely used renal function tests remain normal in uncomplicated
      hypercalciuria. The aim of this study was to assess the value of N-acetyl-beta-D
      glucosaminidase (NAG), a sensitive marker of renal proximal tubular damage, in
      experimental hypercalciuria. Oral calcium providing 75 mg/kg per day elementary
      calcium and 20,000 IU/day vitamin D3 was administered for 15 days to 7 rabbits
      (Orytolagus cuniculus-New Zealand white) and 7 rabbits were given placebo as a
      control group. Serum calcium, phosphorus, and alkaline phosphatase, daily urinary
      calcium excretion and NAG/creatinine ratio were measured before and after drug
      administration. Kidneys were examined macroscopically and microscopically
      following the study period. Serum calcium, phosphorous and urinary calcium
      excretion increased, while alkaline phosphatase decreased significantly in
      response to drug treatment [10.8 +/- 1.5 vs. 12.2 +/- 1.3 mg/dl, 4.6 +/- 0.6 vs.
      6.7 +/- 0.7 mg/ dl, 22.3 +/- 8.3 vs. 46.8 +/- 22.5 mg/kg per day, and 138.0 +/-
      57.1 vs. 70.1 +/- 33.1 IU/l, respectively (P < 0.05)]. The NAG/creatinine ratio
      prior to the study (0.5 +/- 0.1 mU/ mg) was significantly different from that
      after the study (5.4 +/- 1.5 mU/mg, P < 0.01). In the control group, changes in
      serum and urinary parameters were not significant (P > 0.05). The relationship
      between the urinary NAG/ creatinine ratio and the daily urinary calcium excretion
      was statistically significant (r = 0.67, P < 0.05). In the study group,
      nephrocalcinosis was present in all rabbits except 1 (85.7%), whereas none of the
      control group rabbits had nephrocalcinosis. In conclusion, in rabbits urinary NAG
      excretion increases significantly in nephrocalcinosis induced by hypercalciuria.

PMID- 9260251
TI  - Simultaneous pancreas-kidney transplant in two children with hemolytic-uremic
      syndrome.
AB  - Simultaneous pancreas-kidney (SPK) transplantation has rarely been performed in
      the pediatric population. This report describes successful SPK transplantation in
      a 12-year-old girl and a 14-year-old boy with renal and pancreatic insufficiency
      secondary to postdiarrheal hemolytic-uremic syndrome. All reported cases of
      pediatric SPK transplantation are reviewed. SPK transplantation is a feasible
      option in selected pediatric patients with combined pancreatic and renal
      insufficiency.

PMID- 9260253
TI  - Primary hyperoxaluria type I: renal ultrasound before and after treatment.
AB  - Three patients with primary hyperoxaluria type I received therapy consisting of
      vitamin B6, magnesium oxide, and high oral fluid intake. Sonographic follow-up
      showed a variable response to treatment, ranging from normalization of renal
      tissue to no change at all. However, there is evidence of a correlation between
      laboratory findings and ultrasound findings during treatment.

PMID- 9260252
TI  - Immune response to Escherichia coli O157:H7 in hemolytic uremic syndrome
      following salmonellosis.
AB  - Escherichia coli O157:H7, a Shiga-like toxin (SLT)-producing enteric pathogen,
      has been implicated in most cases of post-diarrheal hemolytic uremic syndrome (D
      + HUS). Infection with other bacterial pathogens such as Salmonella has also
      preceded D + HUS episodes, leading to speculation that these organisms may also
      be etiological. We present two children with unrelated D + HUS following
      salmonellosis. Both children had negative stool cultures on sorbitol-MacConkey
      agar soon after the onset of diarrhea. After the diagnosis of HUS, both patients
      had repeat stool cultures positive for Salmonella alone. Polymerase chain
      reactions for SLT I and II gene sequences in Salmonella isolates were negative.
      Enzyme-linked immunosorbent assay for specific humoral response to E. coli
      O157:H7 lipopolysaccharide in acute and convalescent serum samples revealed
      evidence of heretofore undetected E. coli O157:H7 infection contemporaneous with
      each D + HUS episode. These cases demonstrate that isolation of only non-SLT
      producing microbes from children with D + HUS should raise suspicion of
      concurrent undetected infection with SLT-producing organisms. Assaying specific
      immune response to E. coli O157:H7 can be an important epidemiological adjunct.
      Bacterial infection with non-SLT-producing Salmonella may represent concomitant
      enteric pathology rather than D + HUS-instigating infection.

PMID- 9260254
TI  - Renal tubular dysgenesis with microcephaly.
AB  - Renal tubular dysgenesis, a rare, lethal, autosomal recessive disorder, is
      characterized by short and poorly differentiated proximal convoluted tubules
      associated with oligohydramnios, Potter sequence, and neonatal death due to
      respiratory failure. Abnormalities of the skull may occur in some cases. We
      report an infant born of a consanguineous union who also had microcephaly, among
      other features. A history of oligohydramnios with or without skull abnormalities
      and a lethal outcome without obvious explanation should occasion renal
      histological study aimed at precise diagnosis and genetic counselling.

PMID- 9260255
TI  - Neonatal renal failure due to obstructive candidal bezoars.
AB  - Acute renal failure (ARF) developed in a 7-week-old infant due to bilateral
      candidal bezoars (fungal balls) causing obstruction at the pelviureteric
      junction. The baby was born at term with an appropriate birthweight, and had been
      treated with broad-spectrum antibiotics for respiratory distress and septicemia
      during the 1st week of life. Recovery from ARF followed renal decompression with
      bilateral nephrostomy tube placement and parenteral administration of
      amphotericin B and 5-flucytosine.

PMID- 9260256
TI  - Renovascular hypertension in Marfan syndrome.
AB  - A defect in fibrillin integrity predisposes patients with Marfan syndrome to
      vascular wall abnormalities, most notably aortic rupture and dissection. Renal
      vascular anomalies have not been described previously in children with Marfan
      syndrome. In this report, we detail data from a hypertensive 14-year-old girl
      with clinical stigmata of Marfan syndrome and a diagnostic evaluation significant
      for characteristic aortic root dilatation and aneurysm, as well as a disparity in
      renal size and function exacerbated by captopril administration. Renal
      arteriography confirmed a left main renal artery stenosis that was not amendable
      to balloon angioplasty. Surgical resection resulted in significant improvement in
      hypertension. Pathological examination of the resected renal artery segment
      revealed intimal proliferation, fragmentation of the elastic media, and inner
      medial dissection. This patient demonstrates that, in addition to the aorta,
      renal arteries can be affected with the characteristic vascular wall pathology of
      Marfan syndrome, resulting in systemic hypertension. These data suggest that
      children with Marfan syndrome and hypertension need to be evaluated carefully for
      the presence of renal anomalies.

PMID- 9260257
TI  - Syndrome of inappropriate secretion of antidiuretic hormone in nasopharynx
      carcinoma.
AB  - The syndrome of inappropriate secretion of antidiuretic hormone (ADH) or SIADH
      has been reported in various disorders. We report a pediatric patient with
      nasopharynx carcinoma who may have developed a clinical SIADH with severe
      hyponatremia and generalized seizure during the administration of intravenous
      hydration. We propose that the inappropriately high plasma level of ADH led to
      the inability to excrete sufficient amounts of free water during a hyperhydration
      protocol with a relatively hypotonic fluid, which resulted in acute hyponatremia
      and central nervous system involvement. To avoid this complication, intravenous
      hydration before chemotherapy in children with nasopharynx carcinoma should be
      performed at a slower infusion rate and with a sodium chloride concentration of
      more than half isotonic.

PMID- 9260258
TI  - Hereditary vesicoureteric reflux: phenotypic variation and family screening.
AB  - Family screening programs offer the prospect of detecting hereditary
      vesicoureteric reflux before scars develop with urinary infections. This review
      describes minor to severe reflux and reflux nephropathy (RN) in five families
      where a member developed renal failure, including 3 children who developed both
      scars and renal failure. Analysis of families in the literature demonstrated
      similar phenotypic variation and the regular detection of both sterile reflux and
      RN by screening. Future systematic family studies could evaluate the predictive
      value of ultrasound in detecting significant reflux, assess the severity of
      congenital RN found in infants, and compare prophylactic regimes with historic
      controls.

PMID- 9260259
TI  - Renal problems in black South African children.
AB  - Black South African children have an increased prevalence of acute post
      streptococcal glomerulonephritis, focal glomerulosclerosis, hepatitis B
      associated membranous nephropathy, congenital syphilis, congenital nephrotic
      syndrome with Alport-like basement membrane changes and Takayasu's arteritis, but
      a paucity of reflux nephropathy, polycystic kidney disease and non-shigella
      induced haemolytic uraemic syndrome. However, in recent years, the haemolytic
      uraemic syndrome has become more prevalent in black children; this is usually due
      to Shigella dysenteriae type 1, and could indicate a different emphasis in the
      pathogenic mechanism. Focal glomerulosclerosis is the commonest reason for renal
      failure requiring transplantation in black children with rapidly progressive
      glomerulonephritis (usually streptococcal induced) being second. Transplantation
      has been somewhat problematic with a scarcity of kidneys at times, many
      mismatches and poor compliance in the lower socio-economic groups. The
      association of tuberculosis with focal glomerulosclerosis and Takayasu's
      arteritis in black South African children is intriguing. The progression of focal
      glomerulosclerosis is accelerated in those patients with evidence of previous
      tuberculosis, and in Takayasu's arteritis the association is almost absolute as
      experienced locally, with the data suggesting an autoimmune reaction.

PMID- 9260261
TI  - Clinical quiz.

PMID- 9260260
TI  - Renal excretion of endothelin in children.
AB  - Endothelin (ET) is a peptide with profound vasoconstrictive potential. First
      isolated from porcine endothelial cell supernatant, it is produced also by smooth
      muscle, epithelial and circulating cells. Besides vasoconstriction, a wide
      spectrum of biological activities of ET (via activation of membrane receptors)
      has been described. These include regulation of other hormones and
      neurotransmitters, cellular growth and proliferation, bronchoconstriction, and,
      in the kidney, natriuresis and water diuresis. ET exerts its effects mainly in an
      autocrine and paracrine fashion. A high concentration of ET is found in urine,
      compared with plasma originating mainly from the kidney itself. In this review we
      focus on the role of urinary excretion of ET in children. ET excretion was
      determined under different physiological and pathological conditions. In
      premature infants and newborns, the daily excretion of ET (corrected for body
      surface) was higher than in older children; it was constant, and comparable to
      the values in healthy adults after the age of 2 years. Renal ET excretion
      correlated positively with urine flow in both healthy and sick children.
      Conditions with tubular and/or collecting duct cell damage, such as severe
      hypoxia, hemolytic-uremic syndrome, renal transplantation, diabetes mellitus,
      chronic renal failure, and contrast media cytotoxicity were characterized by
      elevated urinary excretion of ET. In conclusion, the renal excretion of ET is
      influenced by several factors, probably reflecting the intrarenal ET production.
      ET has a low specificity with regard to renal injury.

PMID- 9260262
TI  - Hyponatraemia and cerebral convulsion after a single dose of intranasal DDAVP.

PMID- 9260263
TI  - Growth hormone treatment increases kidney size in a woman with growth hormone
      deficiency--a case report.

PMID- 9260264
TI  - Is there an indication for desensitization therapy (venom immunotherapy) in a
      transplanted child with bee venom allergy? What are the risks and chances of
      success?

PMID- 9260265
TI  - Search for novel leads for histamine H3-receptor antagonists: amine derivatives.
AB  - In search for novel leads for histamine H3-receptor antagonists a number of amine
      derivatives of different (1 H-imidazol-4-yl)anilines and omega-(1 H-imidazol-4
      yl)alkanamines were prepared. Pharmacological in vitro H3-receptor investigations
      of the prepared urea, amide, inverse amide, thioamide, and thiourea derivatives
      on synaptosomes of rat cerebral cortex proved that the aniline derivatives are
      inactive at H3-receptors, whereas derivatives of the omega-(1 H-imidazol-4-yl)
      alkanamines showed moderate to good activity. Some compounds are active in the
      nanomolar concentration range. The most potent compounds in this series are the
      thioamide derivative 7 and the urea derivatives 11, 12 of 3-(1 H-imidazol-4-yl)
      propanamine. Therefore, the urea derivatives were tested in vitro on isolated
      organs of the guinea pig for their activity on the other two histamine receptor
      subtypes proving their high selectivity. In vivo studies of the effects of the
      urea derivatives 11 and 12 on brain Nt-methylhistamine levels, a test of central
      H3-receptor activity after peroral application to mice, showed no detectable
      activity. Thus, the urea type antagonists are useful potent and selective H3
      receptor tools for in vitro studies and for investigations of ligand-receptor
      interactions.

PMID- 9260267
TI  - High performance liquid chromatographic analysis of selected sulfonamides in
      plasma.
AB  - Chromatographic conditions were elaborated to evaluate a model mixture of four
      sulfonamides (sulfamethoxazole, sulfamoxole, sulfisoxazole and
      sulfamethoxydiazine) in plasma using a reversed phase HPLC C18 column and a
      mobile phase composed of methanol and phosphate buffer (60:40; v/v) at pH 5.0.
      The detection was made using an electrochemical detection with the potential set
      at 1.1 V. In the case of sulfonamides deproteination of plasma with methanol was
      more advantageous than extraction with organic solvents. The recovery of analysed
      sulfonamides was in the range of 95-97%, the detection limits were 10 ng/ml of
      plasma.

PMID- 9260266
TI  - 5-HT1A and 5-HT2A receptor affinity and functional profile of some N-[3-(4-aryl-1
      piperazinyl)propyl] derivatives of indolin-2(1H)-one, quinolin-2(1 H)-one and
      isoquinolin-1(2H)-one. Part 30: Structure-activity relationship studies of CNS
      agents.
AB  - A series of new 1-aryl-4-propylpiperazines containing the modified terminal amide
      fragment 9, 15-19, 21, 23 and 25 were synthesized and their 5-HT1A and 5-HT2A
      receptor affinities were determined. All the compound were highly potent 5-HT1A
      receptor ligands with a diverse 5-HT2A receptor affinity. It was found that the 5
      HT2A receptor affinity depends on the dipole moment and lipophilicity of amide
      moiety. Compound 9b was found to be a 5-HT2A receptor antagonist and a weak 5
      HT1A receptor agonist.

PMID- 9260268
TI  - Unsaturated glycerol monoethers as novel skin penetration enhancers.
AB  - A mixture of glycerol monoethers was extracted from the liver oil of deep sea
      shark (Centroporus squamosus). It consisted mainly of monoethers of glycerol and
      linear monounsaturated octadecanol, and glycerol and linear monounsaturated
      hexadecanol. Only about 11% of the extract consisted of glycerol monoethers
      derived from linear saturated fatty alcohols. The glycerol monoether extract was
      somewhat less effective as skin penetration enhancer than oleic acid and other
      potent fatty acid penetration enhancers, but it was still a very effective
      enhancer in the hairless mouse skin model used in this study.

PMID- 9260269
TI  - Preliminary studies on the antiinflammatory, analgesic and diuretic activity of
      stagninol, a sesquiterpene isolated from Persicaria stagnina.
AB  - Stagninol, a sesquiterpene, isolated from Persicaria stagnina Linn showed
      significant antiinflammatory and analgesic activity (P < 0.001) in animals. A
      sedative action of stagninol was revealed by a marked potentiation of
      pentobarbital induced sedation with significant effect on both onset (P < 0.001)
      and duration (P < 0.01) of sleep. Measurement of urine volume after
      administration of stagninol indicated its significant diuretic action.
      Biochemical investigations revealed that both crude extract and stagninol showed
      dose dependent reduction of blood uric acid and blood urea nitrogen (BUN). There
      was an increase in serum glutamic pyruvic transaminase (SGPT) and serum alkaline
      phosphatase (SAP) level with the crude extract but stagninol showed no
      significant changes of serum glutamic oxaloacetic transaminase (SGOT), SGPT and
      SAP level.

PMID- 9260270
TI  - Esculetin in Alchemilla speciosa: identification and antimutagenic properties.
AB  - Quercetin, an ubiquitously occurring plant mutagen was detected and quantified in
      a methanolic extract prepared from the herb of Alchemilla speciosa BUSER
      (Rosaceae). However, the extract exhibited much less mutagenicity in Salmonella
      typhimurium than expected from its quercetin content. A bioassay guided
      fractionation resulted in a crude fraction in which esculetin was present, as
      evidenced by GC/MS analysis. This coumarin derivative was detected for the first
      time in an Alchemilla species. It was at least partly responsible for the
      inhibition of the quercetin mutagenicity. Esculetin was also found to be active
      against certain mutagens which need metabolic activation. Its activity was
      comparable or even more pronounced than that of other plant coumarins.

PMID- 9260271
TI  - EMD 95885, a new eliprodil analogue with higher affinity for the N-methyl-D
      aspartate (NMDA) receptor.

PMID- 9260272
TI  - Relationship between the structure of some 1,4-piperazine derivatives of
      aryloxyaminopropanos and their Ca-antagonistic activity.

PMID- 9260273
TI  - Structural determinants of specificity in the cysteine protease cruzain.
AB  - The structure of cruzain, an essential protease from the parasite Trypanosoma
      cruzi, was determined by X-ray crystallography bound to two different covalent
      inhibitors. The cruzain S2 specificity pocket is able to productively bind both
      arginine and phenylalanine residues. The structures of cruzain bound to benzoyl
      Arg-Ala-fluoromethyl ketone and benzoyl-Tyr-Ala-fluoromethyl ketone at 2.2 and
      2.1 A, respectively, show a pH-dependent specificity switch. Glu 205 adjusts to
      restructure the S2 specificity pocket, conferring right binding to both
      hydrophobic and basic residues. Kinetic analysis of activated peptide substrates
      shows that substrates placing hydrophobic residues in the specificity pocket are
      cleaved at a broader pH range than hydrophilic substrates. These results
      demonstrate how cruzain binds both basic and hydrophobic residues and could be
      important for in vivo regulation of cruzain activity.

PMID- 9260274
TI  - The X-ray structure of a mutant eye lens beta B2-crystallin with truncated
      sequence extensions.
AB  - beta-Crystallins are oligomeric eye lens proteins that are related to monomeric
      gamma-crystallins by domain swapping: like gamma-crystallins, they are comprised
      of two similar domains but they differ in having long sequence extensions. beta
      B2, a major component of beta-crystallin oligomers, self-associates to a
      homodimer in solution. In two crystal structures of native beta B2, the protein
      is a 222-symmetric tetramer of eight domains. It has previously been shown that a
      mutant of rat beta B2-crystallin, in which the bulk of the N- and C-terminal
      sequence extensions has been deleted, assembles into dimers and tetramers. Here
      we present the 3.0 A resolution X-ray structure of the tetramer, beta B2 delta
      NC1. The mutant tetramer has a very similar set of domain interactions to the
      native structure. However, the structures differ in the relative orientation of
      the two sets of four domains. The paired N- and C-terminal domain interface,
      which is at the heart of the dimer structure, is very similar to the native
      structure. However, the truncation of the C-terminal extension removes an
      important tryptophan residue, which prevents the extension from acting as a (non
      covalent) linker, as it does in native beta B2. There is a knock-on structural
      effect that removes a contact between extension and covalent linker, and this
      appears to cause a small twist in the linker that is amplified into a 20 degrees
      rotation between sets of paired domains.

PMID- 9260275
TI  - Comparison of straight chain and cyclic unnatural amino acids embedded in the
      core of staphylococcal nuclease.
AB  - We have determined by X-ray crystallography the structures of several variants of
      staphylococcal nuclease with long flexible straight chain and equivalent length
      cyclic unnatural amino acid side chains embedded in the protein core. The
      terminal atoms in the straight side chains are not well defined by the observed
      electron density even though they remain buried within the protein interior. We
      have previously observed this behavior and have suggested that it may arise from
      the addition of side-chain vibrational and oscillational motions with each bond
      as a side chain grows away from the relatively rigid protein main chain and/or
      the population of multiple rotamers (Wynn R, Harkins P, Richards FM. Fox RO.
      1996. Mobile unnatural amino acid side chains in the core of staphylococcal
      nuclease. Protein Sci 5:1026-1031). Reduction of the number of degrees of freedom
      by cyclization of a side chain would be expected to constrain these motions.
      These side chains are in fact well defined in the structures described here. Over
      packing of the protein core results in a 1.0 A shift of helix 1 away from the
      site of mutation. Additionally, we have determined the structure of a side chain
      containing a single hydrogen to fluorine atom replacement on a methyl group. A
      fluorine atom is intermediate in size between methyl group and a hydrogen atom.
      The fluorine atom is observed in a single position indicating it does not rotate
      like methyl hydrogen atoms. This change also causes subtle differences in the
      packing interactions.

PMID- 9260276
TI  - Identification of cooperative folding units in a set of native proteins.
AB  - Cooperative unfolding penalties are calculated by statistically evaluating an
      ensemble of denatured states derived from native structures. The ensemble of
      denatured states is determined by dividing the native protein into short
      contiguous segments and defining all possible combinations of native, i.e.,
      interacting, and non-native, i.e., non-interacting, segments. We use a novel
      knowledge-based scoring function, derived from a set of non-homologous proteins
      in the Protein Data Bank, to describe the interactions among residues. This
      procedure is used for the structural identification of cooperative folding cores
      for four globular proteins: bovine pancreatic trypsin inhibitor, horse heart
      cytochrome c, French bean plastocyanin, and staphylococcal nuclease. The
      theoretical folding units are shown to correspond to regions that exhibit
      enhanced stability against denaturation as determined from experimental hydrogen
      exchange protection factors. Using a sequence similarity score for related
      sequences, we show that, in addition to residues necessary for enzymatic
      function, those amino acids comprising structurally important folding cores are
      also preferentially conserved during evolution. This implies that the identified
      folding cores may be part of an array of fundamental structural folding units.

PMID- 9260277
TI  - Functional and receptor binding characterization of recombinant murine macrophage
      inflammatory protein 2: sequence analysis and mutagenesis identify receptor
      binding epitopes.
AB  - Murine macrophage inflammatory protein-2 (MIP-2), a member of the alpha-chemokine
      family, is one of several proteins secreted by cells in response to
      lipopolysaccharide. Many of the alpha-chemokines, such as interleukin-8, gro
      alpha/MGSA, and neutrophil activating peptide-2 (NAP-2), are associated with
      neutrophil activation and chemotaxis. We describe the expression, purification,
      and characterization of murine MIP-2 from Pichia pastoris. Circular dichroism
      spectroscopy reveals that MIP-2 exhibits a highly ordered secondary structure
      consistent with the alpha/beta structures of other chemokines. Recombinant MIP-2
      is chemotactic for human and murine neutrophils and up-regulates cell surface
      expression of Mac-1. MIP-2 binds to human and murine neutrophils with
      dissociation constants of 6.4 nM and 2.9 nM, respectively. We further
      characterize the binding of MIP-2 to the human types A and B IL-8 receptors and
      the murine homologue of the IL-8 receptor. MIP-2 displays low-affinity binding to
      the type A IL-8 receptor (Kd > 120 nM) and high-affinity binding to the type B IL
      8 receptor (Kd 5.7 nM) and the murine receptor (Kd 6.8 nM). The three-dimensional
      structure of IL-8 and sequence analysis of six chemokines (IL-8, gro-alpha, NAP
      2, ENA-78, KC, and MIP-2) that display high-affinity binding to the IL-8 type B
      receptor are used to identify an extended N-terminal surface that interacts with
      this receptor. Two mutants of MIP-2 establish that this region is also involved
      in binding and activating the murine homologue of the IL-8 receptor. Differences
      in the sequence between IL-8 and related chemokines identify a unique
      hydrophobic/aromatic region surrounded by charged residues that is likely to
      impart specificity to IL-8 for binding to the type A receptor.

PMID- 9260278
TI  - The extracellular domain of immunodeficiency virus gp41 protein: expression in
      Escherichia coli, purification, and crystallization.
AB  - The env gene of SIV and HIV-1 encodes a single glycoprotein gp 160, which is
      processed to give a noncovalent complex of the soluble glycoprotein gp120 and the
      transmembrane glycoprotein gp41. The extracellular region (ectodomain), minus the
      N-terminal fusion peptide, of gp41 from HIV-1 (residues 27-154) and SIV (residues
      27-149) have been expressed in Escherichia coli. These insoluble proteins were
      solubilized and subjected to a simple purification and folding scheme, which
      results in high yields of soluble protein. Purified proteins have a trimeric
      subunit composition and high alpha-helical content, consistent with the predicted
      coil-coil structure. SIV gp41 containing a double cysteine mutation was
      crystallized. The crystals are suitable for X-ray structure determination and,
      preliminary analysis, together with additional biochemical evidence, indicates
      that the gp41 trimer is arranged as a parallel bundle with threefold symmetry.

PMID- 9260279
TI  - Bayesian statistical analysis of protein side-chain rotamer preferences.
AB  - We present a Bayesian statistical analysis of the conformations of side chains in
      proteins from the Protein Data Bank. This is an extension of the backbone
      dependent rotamer library, and includes rotamer populations and average chi
      angles for a full range of phi, psi values. The Bayesian analysis used here
      provides a rigorous statistical method for taking account of varying amounts of
      data. Bayesian statistics requires the assumption of a prior distribution for
      parameters over their range of possible values. This prior distribution can be
      derived from previous data or from pooling some of the present data. The prior
      distribution is combined with the data to form the posterior distribution, which
      is a compromise between the prior distribution and the data. For the chi 2, chi
      3, and chi 4 rotamer prior distributions, we assume that the probability of each
      rotamer type is dependent only on the previous chi rotamer in the chain. For the
      backbone-dependence of the chi 1 rotamers, we derive prior distributions from the
      product of the phi-dependent and psi-dependent probabilities. Molecular mechanics
      calculations with the CHARMM22 potential show a strong similarity with the
      experimental distributions, indicating that proteins attain their lowest energy
      rotamers with respect to local backbone-side-chain interactions. The new library
      is suitable for use in homology modeling, protein folding simulations, and the
      refinement of X-ray and NMR structures.

PMID- 9260280
TI  - Thermodynamic analysis of the effect of selective monodeamidation at asparagine
      67 in ribonuclease A.
AB  - Selective deamidation of proteins and peptides is a reaction of great interest,
      both because it has a physiological role and because it can cause alteration in
      the biological activity, local folding, and overall stability of the protein. In
      order to evaluate the thermodynamic effects of this reaction in proteins, we
      investigated the temperature-induced denaturation of ribonuclease A derivatives
      in which asparagine 67 was selectively replaced by an aspartyl residue or an
      isoaspartyl residue, as a consequence of an in vitro deamidation reaction.
      Differential scanning calorimetry measurements were performed in the pH range 3.0
      6.0, where the unfolding process is reversible, according to the reheating
      criterion used. It resulted that the monodeamidated forms have a different
      thermal stability with respect to the parent enzyme. In particular, the
      replacement of asparagine 67 with an isoaspartyl residue leads to a decrease of
      6.3 degrees C of denaturation temperature and 65 kJ mol-1 of denaturation
      enthalpy at pH 5.0. These results are discussed and correlated to the X-ray three
      dimensional structure of this derivative. The analysis leads to the conclusion
      that the difference in thermal stability between RNase A and (N67isoD)RNase A is
      due to enthalpic effects arising from the loss of two important hydrogen bonds in
      the loop containing residue 67, partially counterbalanced by entropic effects.
      Finally, the influence of cytidine-2'-monophosphate on the stability of the three
      ribonucleases at pH 5.0 is studied and explained in terms of its binding on the
      active site of ribonucleases. The analysis makes it possible to estimate the
      apparent binding constant and binding enthalpy for the three proteins.

PMID- 9260281
TI  - The role of PII conformations in the calculation of peptide fractional helix
      content.
AB  - Changes in the temperature, pH, ionic strength, or denaturant concentration of
      aqueous solutions of the monomeric non-alpha-helical peptide
      acetylYEAAAKEAPAKEAAAKAamide generate changes in its dichroic spectrum
      characteristic for a conformational transition. This transition has the
      characteristic features of a residue PII/unstructured conformational equilibrium
      in which PII denotes an extended left-handed helical conformation and
      unstructured denotes all the remaining conformations in a random coil ensemble.
      Replacement of the proline residue facilitates population of residues in an alpha
      helical conformation. However, the ellipticity values for these non-proline
      peptides merge with the ellipticity of the proline peptide as the population of
      residues in the alpha-helix conformation is diminished. This convergence suggests
      that all residues in a host/guest peptide series of the same length share a
      common PII/unstructured conformational equilibrium in a given solvent. We propose
      that the fractional helix content of peptides within such a series may be
      estimated by using a two-state calculation in which the ellipticity for the non
      alpha-helix conformations is provided by a peptide having a central proline guest
      residue.

PMID- 9260282
TI  - Coupling backbone flexibility and amino acid sequence selection in protein
      design.
AB  - Using a protein design algorithm that considers side-chain packing
      quantitatively, the effect of explicit backbone motion on the selection of amino
      acids in protein design was assessed in the core of the streptococcal protein G
      beta 1 domain (G beta 1). Concerted backbone motion was introduced by varying G
      beta 1's supersecondary structure parameter values. The stability and structural
      flexibility of seven of the redesigned proteins were determined experimentally
      and showed that core variants containing as many as 6 of 10 possible mutations
      retain native-like properties. This result demonstrates that backbone flexibility
      can be combined explicitly with amino acid side-chain selection and that the
      selection algorithm is sufficiently robust to tolerate perturbations as large as
      15% of G beta 1's native supersecondary structure parameter values.

PMID- 9260283
TI  - The membrane topology of the amino-terminal domain of the red cell calcium pump.
AB  - A systematic study of the membrane-associated regions in the plasma membrane Ca2+
      pump of erythrocytes has been performed by hydrophobic photolabeling. Purified
      Ca2+ pump was labeled with 3-(trifluoromethyl)-3-(m-[125I]iodophenyl)-diazirine
      ([125I]TID), a generic photoactivatable hydrophobic probe. These results were
      compared with the enzyme labeled with a strictly membrane-bound probe, [3H]bis
      phosphatidylethanolamine (trifluoromethyl) phenyldiazirine. A significant light
      dependent labeling of an M(r) 135,000-140,000 peptide, corresponding to the full
      Ca2+ pump, was observed with both probes. After proteolysis of the pump labeled
      with each probe and isolation of fragments by SDS-PAGE, a common pattern of
      labeled peptides was observed. Similarly, labeling of the Ca2+ pump with
      [125I]TID, either in isolated red blood cell membranes or after the enzyme was
      purified, yields a similar pattern of labeled peptides. Taken together, these
      results validate the use of either probe to study the lipid interface of the
      membrane-embedded region of this protein, and sustain the notion that the
      conformation of the pump is maintained throughout the procedures of
      solubilization, affinity purification, and reconstitution into proteoliposomes.
      In this work, we put special emphasis on a detailed analysis of the N-terminal
      domain of the Ca2+ pump. A labeled peptide of M(r) 40,000 belonging to this
      region was purified and further digested with V8 protease. The specific
      incorporation of [125I]TID to proteolytic fragments pertaining to the amino
      terminal region indicates the existence of two transmembrane stretches in this
      domain. A theoretical analysis based on the amino acid sequence 1-322 predicts
      two segments with high probability of membrane insertion, in agreement with the
      experimental data. Each segment shows a periodicity pattern of hydrophobicity and
      variability compatible with alpha-helical structure. These results strongly
      suggest the existence of a transmembrane helical hairpin motif near the N
      terminus of the Ca2+ pump.

PMID- 9260284
TI  - Xylanase XynA from the hyperthermophilic bacterium Thermotoga maritima: structure
      and stability of the recombinant enzyme and its isolated cellulose-binding
      domain.
AB  - The hyperthermophilic bacterium Thermotoga maritima is capable of gaining
      metabolic energy utilizing xylan. XynA, one of the corresponding hydrolases
      required for its degradation, is a 120-kDa endo-1,4-D-xylanase exhibiting high
      intrinsic stability and a temperature optimum approximately 90 degrees C.
      Sequence alignments with other xylanases suggest the enzyme to consist of five
      domains. The C-terminal part of XynA was previously shown to be responsible for
      cellulose binding (Winterhalter C, Heinrich P, Candussio A, Wich G, Liebl W.
      1995. Identification of a novel cellulose-binding domain within the multi-domain
      120 kDa Xylanase XynA of the hyperthermophilic bacterium Thermotoga maritima. Mol
      Microbiol 15:431-444). In order to characterize the domain organization and the
      stability of XynA and its C-terminal cellulose-binding domain (CBD), the two
      separate proteins were expressed in Escherichia coli. CBD, because of its
      instability in its ligand-free form, was expressed as a glutathione S-transferase
      fusion protein with a specific thrombin cleavage site as linker. XynA and CBD
      were compared regarding their hydrodynamic and spectral properties. As taken from
      analytical ultracentrifugation and gel permeation chromatography, both are
      monomers with 116 and 22 kDa molecular masses, respectively. In the presence of
      glucose as a ligand, CBD shows high intrinsic stability.
      Denaturation/renaturation experiments with isolated CBD yield > 80% renaturation,
      indicating that the domain folds independently. Making use of fluorescence
      emission and far-UV circular dichroism in order to characterize protein
      stability, guanidine-induced unfolding of XynA leads to biphasic transitions,
      with half-concentrations c1/2 (GdmCl) approximately 4 M and > 5 M, in accordance
      with the extreme thermal stability. At acid pH, XynA exhibits increased
      stability, indicated by a shift of the second guanidine-transition from 5 to 7 M
      GdmCl. This can be tentatively attributed to the cellulose-binding domain.
      Differences in the transition profiles monitored by fluorescence emission and
      dichroic absorption indicate multi-state behavior of XynA. In the case of CBD, a
      temperature-induced increase in negative ellipticity at 217 nm is caused by
      alterations in the environment of aromatic residues that contribute to the far-UV
      CD in the native state.

PMID- 9260285
TI  - The effect of denaturants on protein structure.
AB  - Virtually all studies of the protein-folding reaction add either heat, acid, or a
      chemical denaturant to an aqueous protein solution in order to perturb the
      protein structure. When chemical denaturants are used, very high concentrations
      are usually necessary to observe any change in protein structure. In a solution
      with such high denaturant concentrations, both the structure of the protein and
      the structure of the solvent around the protein can be altered. X-ray
      crystallography is the obvious experimental technique to probe both types of
      changes. In this paper, we report the crystal structures of dihydrofolate
      reductase with urea and of ribonuclease A with guanidinium chloride. These two
      classic denaturants have similar effects on the native structure of the protein.
      The most important change that occurs is a reduction in the overall thermal
      factor. These structures offer a molecular explanation for the reduction in
      mobility. Although the reduction is observed only with the native enzyme in the
      crystal, a similar decrease in mobility has also been observed in the unfolded
      state in solution (Makhatadze G, Privalov PL. 1992. Protein interactions with
      urea and guanidinium chloride: A calorimetric study.

PMID- 9260286
TI  - Heteronuclear NMR assignments and secondary structure of the coiled coil
      trimerization domain from cartilage matrix protein in oxidized and reduced forms.
AB  - The C-terminal oligomerization domain of chicken cartilage matrix protein is a
      trimeric coiled coil comprised of three identical 43-residue chains. NMR spectra
      of the protein show equivalent magnetic environments for each monomer, indicating
      a parallel coiled coil structure with complete threefold symmetry. Sequence
      specific assignments for 1H-, 15N-, and 13C-NMR resonances have been obtained
      from 2D 1H NOESY and TOCSY spectra, and from 3D HNCA, 15N NOESY-HSQC, and HCCH
      TOCSY spectra. A stretch of alpha-helix encompassing five heptad repeats (35
      residues) has been identified from intra-chain HN-HN and HN-H alpha NOE
      connectivities. 3JHNH alpha coupling constants, and chemical shift indices. The
      alpha-helix begins immediately downstream of inter-chain disulfide bonds between
      residues Cys 5 and Cys 7, and extends to near the C-terminus of the molecule. The
      threefold symmetry of the molecule is maintained when the inter-chain disulfide
      bonds that flank the N-terminus of the coiled coil are reduced. Residues Ile 21
      through Glu 36 show conserved chemical shifts and NOE connectivities, as well as
      strong protection from solvent exchange in the oxidized and reduced forms of the
      protein. By contrast, residues Ile 10 through Val 17 show pronounced chemical
      shift differences between the oxidized and reduced protein. Strong chemical
      exchange NOEs between HN resonances and water indicate solvent exchange on time
      scales faster than 10 s, and suggests a dynamic fraying of the N-terminus of the
      coiled coil upon reduction of the disulfide bonds. Possible roles for the
      disulfide crosslinks of the oligomerization domain in the function of cartilage
      matrix protein are proposed.

PMID- 9260287
TI  - Determination of the binding frame of the chaperone SecB within the physiological
      ligand oligopeptide-binding protein.
AB  - Chaperone proteins demonstrate the paradoxical ability to bind ligands rapidly
      and with high affinity but with no apparent sequence specificity. To learn more
      about this singular property, we have mapped the binding frame of the chaperone
      SecB from E. coli on the oligopeptide-binding protein. Similar studies performed
      on the maltose-binding and galactose-binding proteins revealed centrally
      positioned binding frames of approximately 160 aminoacyl residues. The work
      described here shows that OppA, which is significantly longer than the previously
      studied ligands, has a binding frame that covers 460 amino acids, nearly the
      entire length of the protein. We propose modes of binding to account for the
      data.

PMID- 9260288
TI  - Dimethyl sulfoxide binding to globular proteins: a nuclear magnetic relaxation
      dispersion study.
AB  - The 2H magnetic relaxation dispersion (NMRD) technique was used to characterize
      interactions of dimethyl sulfoxide (DMSO) with globular proteins. A difference
      NMRD experiment involving the N-acetylglucosamine trisaccharide inhibitor,
      demonstrated that the DMSO 2H NMRD profile in lysozyme solution is due to a
      single DMSO molecule bound in the active cleft, with a molecular order parameter
      of 0.47 +/- 0.05 and a residence time in the range 10 ns to 5 ms. With the aid of
      transverse 2H relaxation data, the upper bound of the residence time was further
      reduced to 100 microns. A 1H shift titration experiment was also performed,
      yielding a binding constant of 2.3 +/- 0.3 M-1 at 27 degrees C. In contrast to
      lysozyme, no DMSO dispersion was observed for bovine pancreatic trypsin inhibitor
      (BPTI), indicating that a stable DMSO-protein complex requires a cleft of
      appropriate geometry in addition to hydrogen-bond and hydrophobic interactions.

PMID- 9260289
TI  - An unexpected structural relationship between integral membrane phosphatases and
      soluble haloperoxidases.
AB  - The mechanism of a membrane-bound enzyme important in phospholipid signaling,
      type 2 phosphatidic acid phosphatase, is suggested by sequence motifs shared with
      a soluble vanadium-dependent chloroperoxidase of known structure. These regions
      are also conserved in other soluble globular and membrane-associated proteins,
      including bacterial acid phosphatases, mammalian glucose-6-phosphatases, and the
      Drosophila developmental protein Wunen. This implies that a similar arrangement
      of catalytic residues specifies the active site within both soluble and membrane
      spanning domains.

PMID- 9260290
TI  - CD6 recognizes the neural adhesion molecule BEN.
AB  - CD6 and its ligand activated leukocyte cell adhesion molecule (ALCAM, CD166) have
      been detected on various immune cells and in the brain. CD6-ligand interactions
      have been implicated in the regulation of T cell function. ALCAM shares the same
      extracellular domain organization and significant sequence homology with the
      chicken neural adhesion molecule BEN. Although ALCAM's CD6 binding site is only
      partially conserved in BEN, CD6 specifically binds BEN, albeit with approximately
      10-fold lower avidity than ALCAM. Differences in binding avidity are not detected
      when ALCAM and BEN fusion proteins containing the full-length extracellular
      regions are tested. Homotypic interactions between full-length forms are likely
      to account for these observations. The identified cross-species interaction
      between CD6 and BEN suggests that CD6-ligand interactions are highly conserved.

PMID- 9260291
TI  - Circular dichroism determination of class I MHC-peptide equilibrium dissociation
      constants.
AB  - Class I major histocompatibility complex (MHC) molecules bind peptides derived
      from degraded proteins for display to T cells of the immune system. Peptides bind
      to MHC proteins with varying affinities, depending upon their sequence and
      length. We demonstrate that the thermal stability of the MHC-peptide complex
      depends directly on peptide binding affinity. We use this correlation to develop
      a convenient method to determine peptide dissociation constants by measuring MHC
      peptide complex stability using thermal denaturation profiles monitored by
      circular dichroism.

PMID- 9260292
TI  - Crystallization of 5-aminolaevulinic acid dehydratase from Escherichia coli and
      Saccharomyces cerevisiae and preliminary X-ray characterization of the crystals.
AB  - 5-Aminolaevulinic acid dehydratase (ALAD) catalyzes the formation of
      porphobilinogen from two molecules of 5-aminolaevulinic acid. Both Escherichia
      coli and Saccharomyces cerevisiae ALADs are homo-octameric enzymes which depend
      on Zn2+ for catalytic activity and are potently inhibited by lead ions. The E.
      coli enzyme crystallized in space group I422 (unit cell dimensions a = b = 130.7
      A, c = 142.4 A). The best crystals were obtained in the presence of the
      covalently bound inhibitor laevulinic acid. The yeast enzyme (expressed in E.
      coli) crystallized in the same space group (I422) but with a smaller unit cell
      volume (a = b = 103.7 A, c = 167.7 A). High resolution synchrotron data sets were
      obtained from both E. coli and yeast ALAD crystals by cryocooling to 100 K.

PMID- 9260293
TI  - Multiple conformations of a human interleukin-3 variant.
AB  - Interleukin-3 (IL-3) is a cytokine that stimulates the proliferation and
      differentiation of hematopoietic cells. The hyperactive hIL-3 variant SC-55494
      was shown to have at least two major conformations by high-resolution NMR
      spectroscopy. Mutants of SC-55494 were constructed in which alanine was
      substituted for proline in order to test the hypothesis that proline cis-trans
      isomerization is the source of the observed conformational heterogeneity, as well
      as to evaluate the effect of prolyl peptide bond configuration on biological
      activity. NMR spectra of four single proline-to-alamine mutants (P30A, P31A,
      P33A, and P37A) retain doubled resonances, while spectra of the double mutant
      P30A/P31A and the quadruple mutant P30A/P31A/P33A/ P37A are substantially free of
      heterogeneity. These observations suggest that the two major conformations in SC
      55494 correspond to cis and trans isomers of either or both of the R29-P30 and
      P30-P31 peptide bonds. All six mutants had somewhat lower cell proliferative
      activity than SC-55494, with relative activities ranging from 40 to 80%. The P37A
      mutant has a binding affinity to the low-affinity IL-3 receptor alpha-subunit
      statistically equivalent to SC-55494, while P30A, P31A, and P33A each had about
      two-fold decreases, and P30A/P31A and P30A/P31A/P33A/P37A had four-fold
      decreases. These findings suggest an important role for the cis configuration of
      either or both of the R29-P30 and P30-P31 peptide bonds in IL-3 for optimal
      interaction with the receptor alpha-subunit.

PMID- 9260294
TI  - Use of a fusion protein to obtain crystals suitable for X-ray analysis:
      crystallization of a GST-fused protein containing the DNA-binding domain of DNA
      replication-related element-binding factor, DREF.
AB  - Crystals of glutathione-S-transferase (GST)-fused protein containing the DNA
      binding domain of DNA replication-related element-binding factor, DREF, were
      obtained under crystallization conditions similar to those for GST. Preliminary X
      ray crystallographic analysis revealed that crystals of the GST-fused protein
      belong to space group P6(1)22 or P6(5)22 with unit cell dimensions a = b = 140.4
      A, c = 93.5 A and gamma = 120 degrees, having one molecule in the
      crystallographic asymmetric unit. The crystals diffract to 2.5 A resolution. The
      cell dimensions are related to those of GST crystals thus far reported.
      Crystallization of the DNA-binding domain that was cleaved from the fused protein
      by thrombin was also carried out using several methods under numerous conditions,
      but efforts to produce well-ordered large crystals were unsuccessful. A possible
      application of GST-fusion proteins for small target proteins or domains to obtain
      crystals suitable for X-ray structure determination is proposed.

PMID- 9260295
TI  - Brain protection.

PMID- 9260296
TI  - Results of a Swiss consensus conference on coronary angiography. Members of the
      Swiss Society of Cardiology, Swiss Society of Internal Medicine, Swiss Society of
      Thoracic and Cardiovascular Surgery.
AB  - Coronary angiography is used as a diagnostic procedure to identify patients with
      coronary artery disease who need to undergo revascularization. The quality of its
      indication is widely discussed at present. The Swiss Societies of Cardiology, of
      Internal Medicine and of Thoracic and Cardiovascular Surgery decided to set up a
      consensus conference to evaluate the indications for angiography. For this a
      modified RAND approach (Delphi method) was used. An expert panel rated 374
      indications for coronary angiography twice for appropriateness (more benefits
      than risks for the patient), and once for necessity (procedure has to be offered
      or discussed with the patient). In the panel an agreement percentage of 54% was
      noted. In 40% we observed neither agreement nor disagreement and in 6% we found
      disagreement among the panelists. The necessity ratings showed similar results:
      48% agreement, 46% indetermination and 6% disagreement. The average median rating
      for appropriateness on a 1-9 point scale (1 = extremely inappropriate, 9 =
      extremely appropriate or necessary) was 6.3 over all given single indications and
      7.3 for necessity. The results of appropriateness and necessity ratings presented
      in this paper reflect the findings of a 15-member Swiss panel.

PMID- 9260297
TI  - Results of a Swiss consensus conference on coronary revascularization. Members of
      the Swiss Society of Cardiology, Swiss Society of Internal Medicine, Swiss
      Society of Thoracic and Cardiovascular Surgery.
AB  - Percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass
      grafting (CABG) are major coronary revascularization procedures to relieve
      angina, prevent myocardial infarction and improve long-term survival. The quality
      of their indication is widely discussed at present. The Swiss Societies of
      Cardiology, of Internal Medicine and of Thoracic and Cardiovascular Surgery
      decided to set up a consensus conference to evaluate the indications for coronary
      revascularization. For this a modified RAND approach (Delphi method) was used. An
      expert panel rated 992 indications for coronary revascularization twice for
      appropriateness (more benefits than risks for the patient), and once for
      necessity (procedure has to be offered or discussed with the patient). In the
      panel an agreement percentage of 65% was noted. In 35% we observed neither
      agreement nor disagreement, and there was almost no disagreement among the
      panelists. The results of the necessity ratings were 48% agreement, 49%
      indetermination and 3% disagreement. The average median rating for
      appropriateness on a 1-9 point scale (1 = extremely inappropriate, 9 = extremely
      appropriate or necessary) was 7.7 over all given single indications and 7.2 for
      necessity. The results of appropriateness and necessity ratings presented in this
      paper reflect the findings of a 15-member Swiss panel.

PMID- 9260298
TI  - Suicides and other deaths in police custody.
AB  - This article presents data from a study on 59 deaths in Dutch police stations in
      the period 1983-1993. Twenty deaths were caused by suicide, 19 by intoxications,
      8 by natural causes, and 12 by other or unknown causes. The mortality rate,
      suicide rate, and poisoning rate in police stations were higher than in
      penitentiary institutions and in the general population. The morality rate was
      lower in large police stations than in small police stations. Identification of
      deviant detainees seemed less problematic than handling these deviant detainees.
      It is argued that exceptional detainees without serious charges should be
      transferred to Health Care services. Other structural preventive measures are
      also discussed.

PMID- 9260299
TI  - Correlates of suicidal behavior in a juvenile detention population.
AB  - The present study identifies the correlates of current suicidal ideation and past
      suicide attempt among 555 adolescents in a county juvenile detention center.
      Suicidal behavior in delinquent boys was generally associated with depression and
      decreased social connection, whereas suicidal behavior in delinquent girls was
      associated with impulsivity and instability. Current ideation was most
      significantly associated with current depression. In multivariate analyses, past
      attempts were associated with suicidal ideation and ineffective coping for males,
      with major life events and impulsivity for females, and with not residing with at
      least one biological parent prior to detention for both males and females.

PMID- 9260300
TI  - Patients' reactions to the suicide of a psychotherapist.
AB  - This descriptive exploratory study examines the behavioral and affective
      reactions of clients to the suicide of their psychotherapist 1 year after the
      event, including remembered responses upon first hearing of the suicide. Initial
      grief reactions of participants were found to be similar to other suicide
      survivors with strong attachments to the deceased, including depression,
      numbness, anger, hopelessness, and panic. One year after the event, several
      participants continued to discuss the event with friends, had persistent feelings
      of depression and abandonment, and continued to deny the death as a suicide. A
      reluctance to reenter therapy was also reported. Almost all participants stated
      that suicide was an acceptable solution to some problems. These results suggest
      the potential existence of pathological grief for many participants in this
      study. Implications for the mental health community and intervention services for
      patient survivors are discussed.

PMID- 9260301
TI  - A comparison of suicidal and nonsuicidal elders referred to a community mental
      health center program.
AB  - Sociodemographics, clinical characteristics, and life stressors of community
      dwelling suicidal risk and nonsuicidal risk elders referred to a community aging
      and mental health provider were compared in this study. Information was collected
      through case manager surveys and agency records on 683 older adults referred to
      the Elder Services Program of Spokane Mental Health in 1994 and the first 6
      months of 1995. This sample included 109 individuals who were clinically judged
      to be at suicide risk by case managers at the time of initial assessment.
      Comparisons between suicidal risk and nonsuicidal risk elders indicated that
      suicidal elders were younger, more likely to be separated or divorced, and more
      likely to report a previous history of suicidal behavior. Results of a logistic
      regression analysis indicated that living alone, depression or anxiety disorder,
      and higher levels of emotional disturbance predicted suicide risk status. In
      addition, medical problems, family conflict, and relationship loss predicted
      suicide risk status in this particular sample. Individuals at suicide risk were
      also more likely to have a family physician than others. Implications of findings
      for identification and treatment of suicidal elders are discussed.

PMID- 9260302
TI  - Suicidal ideation in elderly bereaved: the role of complicated grief.
AB  - This study examined whether symptoms of complicated grief at baseline predicted
      suicidal ideation during a depressive episode in elderly bereaved individuals.
      Over a 17-month period, serial ratings of suicidal ideation, hopelessness, and
      symptoms of depression, anxiety, and complicated grief were obtained from 130
      elderly participants who had lost their spouses within the past 2 years. Groups
      of active and passive suicidal ideators, as well as nonideator controls, were
      compared via analysis of variance (ANOVA) with respect to levels of complicated
      grief, depression, and anxiety. Elderly bereaved with both active and passive
      suicidal ideation were found to have higher symptomatic levels of depression,
      hopelessness, complicated grief, and anxiety, as well as lower levels of
      perceived social support, than nonideators at study entry. Fifty-seven percent of
      the patients with high complicated grief scores were found to be ideators during
      the follow-up versus 24% of the patients with low complicated grief scores.
      Patients with any suicidal ideation had higher symptom levels of depression,
      anxiety, and complicated grief when they were ideators as compared with periods
      when they denied ideation. Fifteen out of the 39 ideators had recurrent
      depressive episodes versus 5 of the 91 nonideators. Patients with a history of
      suicide attempts were more likely to be ideators after loss than other bereaved.
      Thus, the condition of having high levels of complicated grief symptoms and
      depressive symptoms appears to make bereaved individuals vulnerable to suicidal
      ideation. Detection of high levels of complicated grief could help clinicians
      identify patients who may be at heightened risk for suicide.

PMID- 9260303
TI  - Ethnocultural differences in prevalence of adolescent suicidal behaviors.
AB  - Data from an ethnically diverse sample of middle school students (grades 6-8; n =
      5,423) are analyzed for ethnic differences in suicidal ideation, thoughts about
      suicide in the past 2 weeks, suicide plans, and suicide attempts. Ideation was
      examined using a four-item scale and a single item on suicidal thoughts. Ideation
      was higher among females, older youths, and lower status youths. The same general
      pattern held for recent suicidal plans and attempts, with the exception of
      gender, where the trend was for males to report more attempts. Lifetime plans and
      attempts were higher for females, older youths, and lower status youths. Data
      were sufficient to compare nine ethnic groups. Multivariate logistic regression
      analyses, adjusting for the effects of age, gender, and socioeconomic status,
      yielded significant odds ratios using the Anglo groups as the reference, for
      suicidal ideation for the Mexican (OR = 1.76, p < .001), Pakistani (OR = 2.0, p <
      .01), and Vietnamese (OR = 1.48, p < .05) American groups. For thoughts about
      suicide in the past 2 weeks, only Pakistani and Mixed Ancestry youths had
      elevated risk. For suicidal plans in the past 2 weeks, Mixed Ancestry youths (OR
      = 2.02, p < .05) and Pakistani youths (OR = 3.20, p < .01) had elevated risk. For
      recent attempts, only the Pakistani American youths had elevated risk (OR = 3.19,
      p < .01). Future research needs to address whether these results hold in other
      ethnically diverse communities and, if so, what factors contribute to increased
      risk among some minority youth and not others.

PMID- 9260304
TI  - Prediction of suicide intent in aboriginal and non-aboriginal adolescent
      inpatients: a research note.
AB  - The relationship among depressive symptoms, anxiety, hopelessness, and suicidal
      intent was explored in a group of 77 adolescents who had been hospitalized after
      attempting suicide. Regression analyses indicated that hopelessness was the only
      significant predictor of suicide intent in Caucasian patients, and depressed mood
      was the only significant predictor in the Aboriginal group. Clinicians should be
      aware that measures of hopelessness may be of limited value in assessing suicidal
      risk in Aboriginal adolescents.

PMID- 9260305
TI  - Ted, suicide in an adolescent storm.

PMID- 9260306
TI  - Crudes of synthesis of neuropeptide Y and beta-amyloid peptide examined by liquid
      chromatography/electrospray tandem mass spectrometry.
AB  - The two peptides, neuropeptide Y (M(r) = 4254) and beta (1-39) amyloid (M(r) =
      4230) are attracting pharmaceutical and biomedical interest for different yet
      equally important reasons. The first is recognized for its various physiological
      functions in the peripheral and central nervous system, while the second has been
      identified as one of the components of the cerebral amyloid deposits
      characteristic of Alzheimer's disease. High level purity of both peptides is
      considered of prime importance for correct interpretation of data obtained by
      biological and pharmaceutical assays and binding tests. Solid-phase synthesis of
      both peptides resulted in crudes of reaction containing both the target peptides
      as well as a number of undesired side products. The use of liquid
      chromatography/electrospray-tandem mass spectrometry (LC/ESI-MS/MS) furnished
      reliable information on the target peptides and provided sequencing information
      on a number of side products. Furthermore, LC/MS/MS data of doubly and triply
      protonated sequences yielded a number of C-terminal fragment ions exhibiting the
      loss of NH3 considered to be an important process for the understanding of
      fragmentation mechanism(s) of multiply protonated peptides.

PMID- 9260307
TI  - Detection of isoprene in expired air from human subjects using proton-transfer
      reaction mass spectrometry.
AB  - A new analytical method using proton-transfer-reaction mass spectrometry (PTRMS)
      is described for the determination of trace constituents in human breath. PTRMS
      is sufficiently sensitive and specific that it does not require preconcentration
      or separation. At its present stage of development it is capable of detecting
      trace constituents present in air at the part-per-billion level. These
      capabilities are illustrated for isoprene, one of the most abundant endogenous
      hydrocarbons. Our results confirm recent observations of a diurnal level
      variation associated with sleep or wakefulness; a new finding is that young
      children have much lower levels of isoprene in breath than adults. To address the
      metabolic origin of human isoprene, we used PTRMS to analyze expired air for
      allylic C5 alcohols that have been proposed to be non-enzymatic precursors of
      isoprene. The lack of correlation between peak breath isoprene and these alcohols
      suggests that the hydrocarbon is formed by some other mechanism.

PMID- 9260308
TI  - The concentrations and bioconcentration factors of mercury in mushrooms from the
      Mierzeja Wislana sand-bar, northern Poland.
AB  - The total concentration of mercury was determined in 15 species of wild growing
      mushrooms, each represented by 15 specimens including underlying substrate,
      collected from the unpolluted area of the sand-bar Mierzeja Wislana in the
      northern part of Poland in 1993-1994. Mercury was measured by cold vapour atomic
      absorption spectrometry (CV-AAS) after wet digestion of the samples with
      concentrated nitric acid in a glass system. The mushroom species examined showed
      a wide range of mercury concentrations, i.e. from 5.6 +/- 2.1 micrograms/g dry
      wt. in Scleroderma citrinum to 1100 +/- 240 micrograms/g in the edible
      Macrolepiota procera. No bioconcentration of mercury was observed in Xerocomus
      badius, Paxilus involutus, Russula queletii and Lactarius rufus. In Hygrophorius
      aurantiaca, Armilariella mellea and Amanita vaginata the bioconcentration factor
      (BCF) values of mercury were close to one. Accumulation of mercury was slight in
      Oudemansiella platyphylla and Amanita citrica (BCF between 2.0 and 3.3 in the
      caps and 1.7 in the stalks) and high in Leccinum scabrurm, Amanita muscaria and
      Macrolepiota procera (BCFs between 11 and 35 in the caps and 6.7-18 in the
      stalks). In the whole fruiting body of Polyporus melanopsuss and Scleroderma
      citrinum the BCF values of mercury were 4.4 and 0.083, respectively. There was a
      high correlation between the concentrations of mercury in the caps and stalks of
      Macrolepiota procera and in the underlying substrate (P < 0.001), a slight
      correlation for Polyporus melanopsuss, and also for the caps of Leccinum scabrum,
      Oudemansiella platyphylla and Russula aeruginea and the stalks of Hygrophoropsis
      aurantiaca (P < 0.01) and L. scabrum (P < 0.05). For the other mushroom species
      investigated there was no correlation between mercury concentration in the
      fruiting bodies and underlying substrate.

PMID- 9260309
TI  - Alternative measures of pesticide use.
AB  - One kilogram of a pesticide is not necessarily equal to a kilogram of a different
      pesticide. This issue can be significant. Whether it is depends on the use to
      which pesticide-use data are put. While kilograms of pesticide is the most common
      way of measuring agricultural chemical use, the type of analysis will generally
      define what measure of chemical use is best. Quantifying the risk from the
      exposure to pesticides, for example, typically requires weighing usage or
      residues by acute or chronic health and environmental toxicity coefficients and
      subsequently estimating human or environmental exposure to such hazards. The
      interferences one draws concerning pesticide use can vary substantially depending
      on the measure considered.

PMID- 9260310
TI  - Serum concentration and dietary intake of Mg and Ca in institutionalized elderly
      people.
AB  - We determined the serum levels and the dietary intake of Mg and Ca in 93
      institutionalized elderly people (24 men and 69 women) in Granada (Spain). The
      serum samples had mean concentrations of 21.39 +/- 2.08 mg/l magnesium and 93.39
      +/- 9.24 mg/l calcium. No significant differences were found in the serum levels
      of the two minerals as regards the sex of the subjects. Application of linear
      regression analysis to the serum Mg and Ca levels showed a statistically
      significant positive correlation (P < 0.05). A low vitamin D intake of these
      subjects (51.8% of the recommended dietary allowance) was observed. The intakes
      of Ca and Mg correlated positively together, as well as with the intakes of
      energy, protein, fibre (in the case of Mg only), iron and phosphorus (P < 0.05).
      The Ca and energy intake were adequate to their current recommendations, as too
      was the Ca:P ratio, whereas the diet had a poor supply of fibre, vitamin D and
      Mg.

PMID- 9260311
TI  - Trichloroethene and tetrachloroethene in ground waters of Zagreb, Croatia.
AB  - At the end of 1986 the presence of chlorinated hydrocarbons was detected in the
      ground water of the industrial area of Zagreb, Croatia. Concentrations of
      trichloroethene and tetrachloroethene were close to or exceeded maximum
      admissible concentrations prescribed by the Public Health Regulations for
      drinking water (30 micrograms/l for trichloroethene and 10 micrograms/l for
      tetrachloroethene). The pumping-site situated within the area had been
      temporarily closed until a water-treatment plant based upon adsorption on
      activated carbon was built. Analysis of the results of adsorption of the
      investigated chlorinated hydrocarbons on activated carbon in granules confirmed a
      remarkably better adsorption of tetrachloroethene compared to trichloroethene. By
      constant monitoring and replacing of saturated carbon at the appropriate time,
      the concentrations of trichloroethene and tetrachloroethene in drinking water
      consumed by approx. 20% of the city population never exceeded maximum admissible
      concentrations in the course of 10 years.

PMID- 9260312
TI  - Long-term extractable compounds screening in surface water to prevent accidental
      organic pollution.
AB  - The organic composition of surface water (a canal network fed by the Rhone river,
      France) was studied over a period of 3 years. The spatial and temporal evolution
      of extractable organic compounds was determined by monitoring the water of the
      principal canal (72 km long) over 3 years and 139 compounds were detected at the
      ng/l concentration level. Using these data the organic fingerprints were
      constructed for every sampling point. These fingerprints depend on sampling dates
      and climatic conditions. Analysed compounds were classified according to two
      criteria: appearance frequency and average concentrations. Three classes were
      defined, corresponding to: organic background, occasional component and chronic
      component. The preponderance of organic background, corresponding to the natural
      organic fingerprint, indicates the high quality of this surface water. The
      proportion of some chemical families were calculated in order to assess their
      anthropogenic impact on the water. This study produced a databank which was
      useful as a reference for the monitoring and checking of water quality. Any
      anomaly disturbing organic fingerprints can thus rapidly be detected and
      identified by comparison with the databank, making better crisis management
      possible.

PMID- 9260313
TI  - [COPD--a neglected disease entity].

PMID- 9260314
TI  - [Coronary disease. Prevention and current therapeutic concepts].

PMID- 9260315
TI  - [Symposium: Intestinal flora in symbiosis and pathogenicity, University of
      Innsbruck, 22 January 1993].

PMID- 9260316
TI  - [Infections in childhood; from respiratory infections to tropical medicine].

PMID- 9260317
TI  - [Schizophrenia: prophylaxis prevents recurrence. Low dose depot neuroleptics--an
      exit from the "revolving door" psychiatry].

PMID- 9260318
TI  - [Cytokine research opens new therapeutic possibilities. Symposium: "Atopic
      dermatitis: New pathogenetic and therapeutic views", Vienna, 18 May 1993].

PMID- 9260319
TI  - [Parkinson disease. Early diagnosis and combined therapy improve prognosis.
      Report from the Symposium: "New and successful attempts at the diagnosis and
      therapy of Parkinson disease"].

PMID- 9260320
TI  - [Study report: management of diarrhea with Smectite. High absorption capacity and
      natural mucosal protection].

PMID- 9260321
TI  - Irish Society of Gastroenterology meeting. 6-7 June 1997. Abstracts.

PMID- 9260322
TI  - Annual meetings of the Irish medical societies. 1995, 1996. Abstracts.

PMID- 9260323
TI  - Which future for ERCP?

PMID- 9260324
TI  - Familial Crohn's disease: a study of 18 families.
AB  - The high frequency of familial Crohn's disease (CD) suggests a genetic
      predisposition. The most recent data from epidemiology and molecular biology are
      consistent with a multifactorial, polygenic inheritance with a possible genetic
      heterogeneity. The aim of our study was, first to compare familial and sporadic
      CD on the basis of the type and location of the disease, and age at diagnosis,
      and second, to evaluate among families, the concordance rate for the type and
      location of the disease. PATIENTS AND METHODS: 18 families with 2 (n = 16) and 3
      (n = 2) affected first degree relatives were studied. They were compared to a
      population of 154 sporadic CD coming from the same gastroenterology unit.
      RESULTS: Age at diagnosis was the same in sporadic and familial CD. There was an
      increased frequency of ileal (p = 0.02), and fibro stenotic (p = 0.005) CD and a
      decreased frequency of colonic (p = 0.006) and inflammatory (p = 0.02) disease,
      in familial CD. There was a significant increase in concordance rate for
      fibrostenotic disease (p < 0.001) and a decrease for inflammatory disease (p <
      0.01), among the families. The observed concordance rate for the location of the
      disease was not significantly different from the expected one. In conclusion,
      these data suggest that CD may be heterogenous and that different clinical
      patterns may be determined either by genetic or environmental factors.

PMID- 9260325
TI  - Transjugular liver biopsy. An experience based on 500 procedures.
AB  - We report our experience based on 500 transjugular liver biopsies, a safe
      procedure even in high risk patients. Transjugular liver biopsies represents one
      third of all liver biopsies performed in our Hepato-Gastroenterology units. Liver
      specimen was adequate to evaluate liver architecture in 87.6% of patients in whom
      a minimal size of 7.6 mm of the liver core was found suitable for this purpose.
      The size of the liver specimen negatively correlated with the increase in hepatic
      venous pressure gradient (p < 0.0001). The liver biopsy was unsuccessful in 3.6%
      of patients. Hepatic capsular perforation occurred in 3.4% of patients but
      remained invariably asymptomatic.

PMID- 9260326
TI  - The immunological basis of inflammatory bowel disease.

PMID- 9260327
TI  - The immune system in inflammatory bowel disease.
AB  - During the last few decades it has become increasingly evident that inflammatory
      bowel disease (IBD) is associated with abnormalities of systemic and mucosal
      immunity. This association has slowly moved from the phenomenological to the
      mechanistic level, and today there is solid evidence that the immune system
      mediates inflammation and tissue damage in the gut of patients suffering from
      IBD. However, the exact mechanisms of injury and what triggers such mechanisms
      are yet to be understood in spite of expanding knowledge of the cellular and
      molecular events underlying gut inflammation. Phenomena detected in the
      peripheral blood of IBD patients reflect some, but not all, of the events
      occurring in the gut and have limited meaning. On the contrary, the investigation
      of phenomena occurring in the inflamed mucosa has yielded valuable information on
      which progress in the understanding of IBD pathogenesis and the development of
      new therapies are currently based. It seems that all immune and non-immune
      components of the mucosa are involved in IBD, either directly or indirectly, as
      shown by abnormalities of humoral and cell-mediated immunity, cytokine and growth
      factor, eicosanoids, neuropeptides, reactive oxygen and nitrogen metabolises,
      cell adhesion molecules, apoptosis, and non-immune cells. Because of the
      multiplicity and complexity of the interactions of all these elements it is
      presently impossible to discern between primary and secondary, and pathogenic and
      non-pathogenic phenomena. In spite of these difficulties, an impressive amount of
      information is being gathered which is translated, at times in a preliminary or
      empirical fashion, into novel immunopathology-based forms of treatment.

PMID- 9260328
TI  - Lessons from genetic models of inflammatory bowel disease.
AB  - Over the past few years, application of targeted gene deletion and transgenic
      approaches has led to the often unanticipated development of rodent lines which
      develop inflammatory bowel disease. While none of these lines recapitulate the
      histopathological and clinical features usually associated with human
      inflammatory bowel disease (IBD) in their entirety, many exhibit key features
      comprising the development of "spontaneous" chronic and acute inflammation. These
      models include targeted deletion of the genes encoding IL-2, IL-10, TGF beta, T
      cell receptor alpha/beta, keratin 8, and Gi2 alpha. In addition, animals
      expressing transgenes for the human WA-B27 (with beta-2 microglobulin) as well as
      a dominant negative construct which functionally blocks N-cadherin have also been
      observed to result in chronic inflammatory bowel disease. Most of the mutant
      murine lines experience a diffuse colitis, but some (HLA-B27 transgenic and IL-10
      deficient) also experience small bowel inflammation. The variety of manipulations
      provides some important broad insights: (1) IBD can result from dysregulation of
      mucosal immune responses or impairment of epithelial barrier function, and (2)
      the natural history of inflammation resulting from mutation at a single genetic
      loci is substantially modulated by other genetic factors. With the rapidly
      increasing variety of mutant mice, comparison of the residual components of
      immune system in lines developing IBD with those of lines not developing IBD, it
      is possible to deduce a requirement for TCR gamma/delta CD4+ lymphocytes as well
      as pivotal role of IFN gamma and (as a suppressive factor) IL-10. Study of a
      number of models has demonstrated the important interaction between environmental
      factors and genetic predisposition. Thus, in at least some of the lines (IL-2
      deficient and HLA-B27) the inflammatory bowel disease is not observed when the
      mutant mice are maintained in a germ-free environment but does develop after
      reconstitution with a pathogen-free flora. In the TCR alpha/beta deficient mice,
      appendectomy in the neonatal period prevents the subsequent development of
      colitis. In still other models, inflammation may not occur without some challenge
      by an exogenous external agent, e.g., mice deficient in intestinal trefoil factor
      (ITF) exposed to dextran sodium sulfate (1). These models offer great promise to
      permit further dissection of the various constituents of the intestinal
      epithelium and mucosal immune response systems which are necessary for
      maintaining normal homeostasis and which can contribute to the development of
      inflammatory bowel disease. Further, they offer powerful tools for exploring the
      interaction between genetic and environmental factors to explicate the
      pathogenesis of inflammatory bowel disease and to develop new therapeutic
      intervention strategies.

PMID- 9260329
TI  - Economic euthanasia.

PMID- 9260330
TI  - Analysing the cost of health.

PMID- 9260331
TI  - The use and abuse of upper digestive endoscopy.

PMID- 9260332
TI  - Experimental hepatitis and role of cytokines.
AB  - Activated T lymphocytes appear to be responsible for liver damage in chronic
      active hepatitis and autoimmune liver disease. We described three experimental
      mouse models of T cell dependent liver injury. D-galactosamine (GalN)-sensitized
      mice challenged with either T cell activating anti-CD3 monoclonal antibody (mAb)
      or with the superantigen staphylococcal enterotoxin B (SEB) developed severe
      liver injury characterized by internucleosomal DNA fragmentation as well as by
      histological hallmarks of hepatocyte apoptosis, both preceding the increase of
      plasma transaminases. Administration of the T cell mitogen concanavalin A (Con A)
      to unsensitized mice also resulted in hepatic apoptosis and the ensuing necrosis.
      Anti-CD3 mAb as well as SEB or Con A induced the release of systemic tumor
      necrosis factor (TNF), interferon gamma (IFN gamma), and various other cytokines.
      Passive immunization against TNF or pretreatment with immunosuppressive drugs
      such as cyclosporin A, FK 506 or dexamethasone protected mice from liver injury.
      T lymphocytes were identified as effector cells of Con A in vivo i) by proof of
      resistance of athyrnic nude mice against Con A and ii) by restoration of
      susceptibility in nude by lymphocyte transfer from control mice. Moreover,
      antibody-dependent depletion of CD4+ T cells fully protected against Con A,
      whereas depletion of CD8+ T cells failed to prevent liver injury. These results
      indicated that cytokines released following T helper cell activation rather than
      cytotoxic T cells mediated liver injury. We recently found that IFN gamma is also
      a critical mediator of Con A-induced hepatic damage. In conclusion, these T cell
      dependent models of inflammatory liver injury allow the investigation of basic
      principles of hepatic disorders associated with T cell activation and
      infiltration as well as pharmacological in vivo studies for the development of
      hepatoprotective drugs.

PMID- 9260333
TI  - Fatal massive liver steatosis--a clinicopathological case report.
AB  - Hepatic fatty change is a common lesion. Two forms are recognized: micro- and
      macrovesicular steatosis, the former being much less frequent and more serious
      than the latter. The case of an alcoholic woman under anticonvulsivant therapy
      and with medications for a syndrome of inappropriate secretion of antidiuretic
      hormone (SIADH) who presented with rapidly progressive cholestasis and
      hepatocellular failure is reported. Massive macro- and micro-vesicular hepatic
      steatosis was diagnosed at autopsy. The authors review the clinico-pathological
      features associated with this condition, and causal factors possibly implicated
      in this case are discussed in regard with currently considered pathophysiological
      mechanisms.

PMID- 9260334
TI  - Giant fibrous polyp of the anal canal.

PMID- 9260335
TI  - The future of advanced practice psychiatric nursing.

PMID- 9260336
TI  - Quality indicators for primary mental health within managed care: a public health
      focus.
AB  - Primary mental health is an orientation to care that addresses mental health
      needs of consumers on point of first contact with caregivers. Core values, and
      principles drawn from a public health perspective serve as the foundation for
      indicators of quality within managed primary mental health. A model, illustrating
      the key components for quality indicators, includes stakeholder groups
      (consumers, families, providers, and payers), quality concerns (access,
      appropriateness, outcomes, and prevention), and the spectrum of clinical
      processes (assessment, treatment, rehabilitation, and support). Responsibility
      for monitoring quality is vested in these stakeholder groups. To enable them to
      fulfill their responsibilities, indicators are proposed in the form of
      checklists. The checklists assist stakeholders in evaluating the plans and
      services offered by managed care entities.

PMID- 9260337
TI  - Advanced practice psychiatric nursing: a national profile.
AB  - The results of a national survey of Advanced Practice Psychiatric Nurses (APPN)
      are presented. Results are based on the Society for Education and Research in
      Psychiatric/Mental Health Nursing's (SERPN) Primary Mental Health and Advanced
      Practice Psychiatric Nursing monograph. Characteristics of the nurses, the
      clients they serve, and their practice patterns are described. Documenting the
      cost-effectiveness of these practitioners and increasing the number of younger
      APPNs is recommended.

PMID- 9260338
TI  - Patient outcomes used by advanced practice psychiatric nurses to evaluate
      effectiveness of practice.
AB  - Health care in the 1990s requires Advanced Practice Psychiatric Nurses (APPNs),
      like other health care providers, to identify and evaluate the outcomes of their
      practices. Many APPNs report that they are not currently engaging in outcome
      evaluation, and many report that they would like more resources on outcome
      measurement. This study identifies outcome evaluations currently in use, through
      an analysis of the responses of 364 Certified Clinical Nurse Specialists in a
      survey conducted by the Society for Education and Research in Psychiatric Nursing
      in 1994-1995. Specific tools that APPNs report using to assess outcomes are also
      identified and referenced.

PMID- 9260339
TI  - Constraints to advanced psychiatric-mental health nursing practice.
AB  - Constraints and barriers to advanced practice psychiatric nursing were reported
      by respondents of the Primary Mental Health and Advanced Practice Psychiatric
      Nursing survey of certified psychiatric clinical nurse specialists. Primary data
      (N = 507) were the qualitative responses to a survey item about constraints and
      secondary data were the literature and theoretical memos. Methodology was based
      on principles of qualitative data analysis and procedures for manifest and latent
      content analysis. Findings resulted in eight themes that explained both
      constraints and barriers to advanced practice: (1) reimbursement, (2)
      prescriptive authority, (3) admitting privileges, (4) bureaucracy, (5) practice
      environment, (6) colleagues, (7) image, and (8) personal. Themes were interpreted
      within the context of regulatory, market-based, and inter/intraprofessional
      constraints and barriers that led to suggestions for organizational and
      individual strategies for action. The survey was funded by the Society for
      Education and Research in Psychiatric-Mental Health Nursing with technical
      support from the Center for Mental Health Services.

PMID- 9260340
TI  - Application of an attribution-affect-action model of caregiving behavior.
AB  - An attribution model was used to examine how staff perceptions of behavior of a
      resident with Alzheimer's disease influenced the way the behavior was managed. A
      sample of 54 female nursing staff members responded to a vignette describing a
      caregiving situation of a demented resident who was not feeding himself or
      herself. Caregiver attribution of resident behavior to reversible causes
      significantly predicted expectations for improved self-feeding in the future, and
      future expectations for self-feeding were significantly related to caregiving
      behavior to encourage self-feeding. Caregivers expected greater participation in
      self-feeding by female residents than by male residents.

PMID- 9260341
TI  - Dissociative identity disorder: a feminist approach to inpatient treatment using
      Jean Baker Miller's Relational Model.
AB  - Women diagnosed with Dissociative Identity Disorder (DID) may experience episodic
      crises characterized by intense states of disconnection from self and others.
      Crises which result in potential harm to self/others may require inpatient
      treatment. With economic emphasis on shorter lengths of stay, a treatment program
      or model which focuses on the DID patient's sense of connectedness to self and
      others can enhance treatment efforts during brief inpatient hospitalizations. The
      Relational Model of Jean Baker Miller uses mutuality and empowerment within the
      therapeutic relationship and inpatient mileu to move the patient beyond
      therapeutic impasse/crisis toward a state of greater connectedness to self and
      others.

PMID- 9260342
TI  - Recovery of the lost good object.
AB  - A significant occurrence in the treatment of some patients involves the recovery
      of the lost good object, that is, recovering a preverbal experience of the "good
      mother." Such an experience can be a turning point in treatment, because it often
      solidifies the therapeutic alliance and thus facilitates a positive outcome.
      Although psychotherapy or psychoanalysis cannot make up for early trauma or
      parental failure, it facilitates the acquisition of positive memories that enable
      the patient to reinvest in the world and in new objects in the environment. This
      thesis is illustrated by material from the author's own analysis, as well as from
      three case examples.

PMID- 9260343
TI  - Impairment of self-representation in schizophrenia: the roles of boundary
      articulation and self-reflexivity.
AB  - Since the time of Kraepelin, clinicians and researchers have regarded
      disturbances in the sense of self as an essential feature of the clinical
      phenomenology of schizophrenia. Through a qualitative analysis of a schizophrenic
      patient's self-descriptions, this article illustrates the roles of boundary
      aberrations and hyperreflexivity (i.e., excessive focus on oneself) in producing
      the identity disturbances associated with this disorder. In this patient's self
      descriptions, reflexive self-awareness resulted in confusion and perplexity, as
      if a core self or basic self-other boundaries were lacking altogether. In
      contrast, a qualitative analysis of a borderline patient's self-descriptions
      suggested that a sense of identity, in turn the result of better boundary
      articulation, was present but unstable and highly reactive to changes in mood.
      Psychotherapeutic implications of impairments in self-representation are
      discussed.

PMID- 9260344
TI  - A controlled study of eye movement desensitization and reprocessing in the
      treatment of posttraumatic stress disordered sexual assault victims.
AB  - Eye movement desensitization and reprocessing (EMDR) is a new method developed to
      treat posttraumatic stress disorder (PTSD). This study evaluated the efficacy of
      EMDR compared to a no-treatment wait-list control in the treatment of PTSD in
      adult female sexual assault victims. Twenty-one subjects were entered, and 18
      completed. Treatment was delivered in four weekly individual sessions.
      Assessments were conducted pre- and posttreatment and 3 months following
      treatment termination by an independent assessor kept blind to treatment
      condition. Measures included standard clinician- and self-administered PTSD and
      related psychopathology scales. Results indicated that subjects treated with EMDR
      improved significantly more on PTSD and depression from pre- to posttreatment
      than control subjects, leading to the conclusion that EMDR was effective in
      alleviating PTSD in this study.

PMID- 9260345
TI  - The process of engaging young people with severe developmental disturbance in
      psychoanalytic psychotherapy: patterns of practice.
AB  - The author discusses some of the problems faced by psychoanalytic
      psychotherapists at a community-based center in engaging in psychotherapy hard-to
      reach young people who present with severe developmental disturbance. The
      difficulties are suggested to arise from a poorly developed capacity, in these
      young people, to reflect on their own and others' mental states. The technical
      implications for the therapeutic approach are discussed. Case material is
      presented that illustrates this approach.

PMID- 9260346
TI  - Parental suicide: a systems perspective.
AB  - In addressing how to treat children after a parent's suicide, most authors focus
      on the individual child's loss and grief. The author examines the need for
      clinicians to expand the treatment focus to include a multidimensional process
      involving the family and the larger social system. A clinical case illustrates an
      integrated treatment approach that addresses the effects of trauma and loss on
      the child, the family, the societal support system, and the therapist, as well as
      on the interactions among these systems.

PMID- 9260347
TI  - Belonging nowhere and everywhere: multiracial identity development.
AB  - Few therapists are trained to work with multiracial individuals. Most have little
      knowledge of the process of identity development in this ever-increasing
      population. In this article, an examination of how the social construction of
      race impacts identity development is followed by a review of current theories
      regarding multiracial identity development. Interviews of clinicians illustrate
      how therapists understand their work with multiracial clients as well as the
      issues they have personally confronted. The challenges faced by therapists
      working with this population center on understanding how oppression affects
      identity development, supporting racial ambiguity as a part of normal identity
      development, working from a nonoppressive theoretical perspective, and examining
      their own internalized rules about racial and ethnic stereotypes. This
      preliminary examination indicates the need for further research. A controlled
      study in this area would be of benefit to the field.

PMID- 9260348
TI  - Transactions of the Topeka Psychoanalytic Society.

PMID- 9260349
TI  - Foot and ankle issues in rheumatoid arthritis.

PMID- 9260350
TI  - Serial bone mineral density studies in the evaluation and management of
      osteoporosis.

PMID- 9260351
TI  - Alternative medicine: where's the evidence?

PMID- 9260352
TI  - Life expectancy.

PMID- 9260353
TI  - The methodologies of qualitative research.

PMID- 9260354
TI  - Use of alternative health care practitioners by Canadians.
AB  - This study focuses on the use of alternative health care practitioners by
      Canadians aged 15 and over using data from the 1994-95 National Population Health
      Survey. A total of 17,626 respondents were selected. Consultation with an
      alternative health care provider or with a chiropractor was deemed to be an
      indicator of the use of alternative health care. In 1994-95, an estimated 15% of
      Canadians aged 15 and over (3.3 million people) used some form of alternative
      health care in the year preceding the survey. Use of alternative health care was
      most prevalent among women, persons aged 45-64 and among higher income groups.
      The use of alternative health care was associated with the number of diagnosed
      chronic illnesses. Among persons free of chronic diseases, 9% consulted
      alternative health care providers compared with 26% of those with three or more
      chronic conditions. Since the population is aging, the proportion with multiple
      chronic illness will also increase, with consequent demand for services from
      alternative health practitioners. The inclusion of any alternative practitioner
      services under existing health care plans could result in higher health care
      costs.

PMID- 9260355
TI  - How different are users and non-users of alternative medicine?
AB  - PURPOSE: To determine whether users and non-users of alternative medicine in the
      province of Quebec differ in terms of demographic characteristics, health profile
      or utilization of medical services. METHODS: The Quebec Health Insurance Board
      (QHIB) medical service records of the Quebec Health Survey (1987) respondents for
      the 12 months before the survey were linked with respondents' survey answers.
      Those who saw an alternative medicine practitioner at their last professional
      consultation (the "users", n = 169) were matched by diagnosis and area of
      residence with those who saw a physician instead (the "non-users", n = 169).
      RESULTS: Users and non-users of alternative medicine differed in age, activity,
      education and income. After adjustment for age, education and income, the two
      groups had a similar health profile, but users of alternative medicine had made
      fewer medical visits in the previous year. CONCLUSION: Alternative medicine
      attracts a particular clientele. More research is needed to understand the
      reasons people look to alternative therapies instead of conventional medicine.

PMID- 9260356
TI  - Mesothelioma surveillance to locate sources of exposure to asbestos.
AB  - To determine whether there were previously unrecognized sources of asbestos
      exposure in British Columbia, incident mesothelioma cases (n = 51) and population
      based controls (n = 154) were interviewed about their occupational histories and
      asbestos exposures. The following occupations were at elevated risk: sheet metal
      workers (OR = 9.6, 95% CI: 1.5-106), plumbers and pipefitters (OR = 8.3, 95% CI:
      1.5-86), shipbuilding workers (OR = 5.0, 95% CI: 1.2-23), painters (OR = 4.5, 95%
      CI: 1.0-24), welders (OR = 3.9, 95% CI: 0.8-22), gardeners (OR = 3.9, 95% CI: 0.8
      22), bricklayers (OR = 3.5, 95% CI: 0.9-14), miners (OR = 3.4, 95% CI: 0.9-13),
      machinists (OR = 3.2, 95% CI: 1.0-11), construction foremen (OR = 3.1, 95% CI:
      0.9-11), and electricians (OR = 3.0, 95% CI: 0.8-12). In a reanalysis excluding
      subjects who worked in occupations or processes considered strongly a priori at
      risk, three groups remained of interest: non-asbestos miners (OR = 9.6, 95% CI:
      1.8-53), bricklayers (OR = 5.4, 95% CI: 1.0-28), and construction labourers (OR =
      2.8, 95% CI: 0.7-10.6).

PMID- 9260357
TI  - Temporal trends in Canadian birth defects birth prevalences, 1979-1993.
AB  - The Canadian Congenital Anomalies Surveillance System monitors birth defects
      reported for stillborns, newborns and infants during the first year of life. Data
      are available through the 1980s and early 1990s for Ontario, Manitoba and
      Alberta, and since 1984 for an additional four provinces. Fifty-seven routine
      monitoring categories and 15 summary categories were examined for temporal
      trends. Comparing the period 1979-1981 with 1991-1993, the reported birth defect
      case birth prevalence increased by 0.2% and the total birth defects birth
      prevalences by 2.5%. The birth prevalence of central nervous system defects
      decreased by 8.2%; the reported birth prevalence increased for congenital heart
      defects by 41%, urinary defects by 127%, Down syndrome by 13% and other
      chromosomal defects by 47%. Further investigation of individual defects would be
      required to evaluate the degree to which changes in reported birth prevalence
      reflect changes including the availability and use of specific diagnostic
      procedures. The work highlights the need to expand the surveillance system to
      include all affected pregnancies where an anomaly has been detected antenatally.

PMID- 9260358
TI  - Age and sex differences in physical inactivity among Ontario teenagers.
AB  - Research on physical activity and fitness indicates their importance in the
      prevention of disease and promotion of health. However, levels of physical
      activity have been shown to vary significantly by age, sex and a wide range of
      additional factors. This paper examines age and sex differences in physical
      inactivity among 13 to 19 year olds participating in the 1990 Ontario Health
      Survey. Findings from the bivariate analysis suggest a major increase in physical
      inactivity between ages 15 and 16. When logistic regression is used to examine
      the adjusted effects of predictor variables on physical inactivity, the effects
      of age remain significant. However, the odds of inactivity at one year increments
      are not significant. There are significant increased odds of inactivity
      associated with such factors as sex, friends' (activity) participation, perceived
      future health problems, and perceived health status. The public health
      implications of the findings suggest that those responsible for developing
      programs and policies to increase physical activity among teenagers should
      consider the critical years of decreased activity and the factors that might
      explain why this decline occurs.

PMID- 9260359
TI  - Mortality in foetal alcohol syndrome.

PMID- 9260360
TI  - School-based hepatitis B immunization program: follow-up of non-participants at
      first school clinic.
AB  - This research project was conducted in the Ottawa-Carleton region of Ontario to
      provide information on reasons why students did not participate in a Grade 7
      hepatitis B school immunization project, and to determine whether telephone
      contact increased attendance at the community catch-up clinics above that
      achieved by a notice sent home with the child from school. A matched comparison
      group design was used. The overall uptake of the first dose of the vaccine in the
      region was 94% of 8,560 eligible students; 90% were immunized at the school
      clinic and 4% at the community catch-up clinic. About 4% of the parents refused
      to have their child immunized at the school or catch-up clinics. Of parents in
      the intervention group 198 (95%) were contacted by phone. The major reasons for
      non-participation at the school clinics were: (1) the child was not at school on
      the clinic day, or the child was sick (51%), (2) there were problems with the
      consent form (21%), and (3) the parents did not know of the program (10%). More
      students from the intervention group (72%) came for vaccination than did those of
      the control group (50%) (p < 0.01).

PMID- 9260362
TI  - Prevalence of tuberculin skin test reactions among prison workers.
AB  - OBJECTIVE: To determine the prevalence of positive tuberculin skin test (TST)
      reactions (10 mm or greater) among full-time employees of a provincial prison for
      women in Montreal. METHODS: Participants underwent tuberculin skin testing and
      completed a self-administered questionnaire. RESULTS: Among 129 employees
      identified, 118 (91%) underwent tuberculin testing. Among 102 born in Quebec who
      completed the questionnaire, 33 (32%) had positive TST reactions, including 12
      (23%) of 52 subjects who had never been vaccinated. Positive TST reactions were
      significantly associated in multivariate analysis with BCG vaccination after
      infancy (OR = 4.5, 95% CI = 1.5-13.5), years of work at other provincial prisons
      (OR = 2.5 for each 5 years of work, 95% CI = 1.2-5.2), travel to tuberculosis
      endemic countries (OR = 7.7, 95% CI = 1.4-43), although not with work in the
      prison for women (OR = 1.3, 95% CI = 0.9-1.9) CONCLUSION: The prevalence of
      positive TST reactions was greater among workers at a provincial prison for women
      than among a sample of students, suggesting increased occupational risk of
      tuberculosis infection.

PMID- 9260361
TI  - Issues in the management of contacts of patients with active pulmonary
      tuberculosis.
AB  - The evidence regarding the transmission of tuberculosis and risk of infection and
      disease in several specific clinical situations has been reviewed. There is
      considerable epidemiologic evidence that contagiousness is not an all-or-nothing
      phenomenon and is affected by several factors, only one of which is the
      bacteriologic status of the patient's sputum. Although untreated smear negative,
      culture positive patients are less contagious on average, they still may transmit
      infection to their close and casual contacts. Compared with contacts with
      tuberculin conversion, persons who are already tuberculin positive have much
      lower risk of developing active tuberculosis after exposure, and persons with
      prior BCG vaccination are at somewhat lower risk. Preventive therapy will be of
      less benefit, but should still be recommended for contacts who are heavily
      exposed or are immune compromised. Epidemiologic studies using RFLP techniques
      could provide more precise answers to the questions in this review.

PMID- 9260363
TI  - The development of a computerized health information system to facilitate program
      planning/evaluation and enhanced First Nations control of community health
      services.
AB  - The Ontario Region of the Medical Services Branch, Health Canada, comprises
      approximately 63,000 First Nations people living on reserve in 126 First Nations
      communities. As of January 1997, 39% of these communities have either assumed
      control of the delivery of health services or are in transfer negotiations with
      the federal government. Another 17% have entered into an Integrated Community
      Based Health Services Agreement with the federal government, which could
      culminate in a full transfer agreement. In order to provide First Nations with
      timely access to health information for case management, program planning and
      evaluation, and the development of their own program priorities at the community
      level, Medical Services Branch, Ontario Region, has worked in partnership with
      First Nations to develop a comprehensive, computerized Health Information System
      (HIS). With direct access to a reliable epidemiological database, First Nations
      will be able to re-profile available resources in response to their own
      identified community health priorities.

PMID- 9260364
TI  - Lack of compliance with hepatitis B vaccination among Canadian STD clinic
      patients: candidates for an accelerated immunization schedule?

PMID- 9260365
TI  - Occupational neurotoxic diseases in Taiwan: a review of the outbreaks and
      clinical features.
AB  - In the past 20 years, several outbreaks of neurotoxic disease due to occupational
      exposure have occurred in Taiwan. The most notorious outbreaks were 'Yu-cheng'
      due to contamination of polychlorinated biphenyls in cooking oil, lead poisoning
      in battery manufacturers and workers in a ship-scrapping yard, tile factory and
      battery recycling plants, and n-Hexane intoxication in press-proffers and ball
      manufacturers. In addition, there were manganese intoxication in ferromanganese
      smelters, mercury intoxication in lamp-socket workers, carbon disulfide
      intoxication in viscose rayon workers and hydrogen sulfide intoxication in
      chemical synthetic plants. Although the incidence of occupational neurotoxic
      diseases has increased, the real incidence is probably still underestimated. The
      reasons for the underestimation include: 1) the education for workers in
      industrial hygiene is inadequate; 2) high risk workers are not screened well; 3)
      physicians are not well trained in early diagnosis of occupational diseases; 4)
      material safety data information is not readily available in the factories; and
      5) the threshold limit values for toxic substances are relatively high in Taiwan,
      compared with other developed countries.

PMID- 9260366
TI  - Factors affecting delection of bleeding lesions in the stomach by initial
      emergency endoscopy.
AB  - BACKGROUND: Accurate endoscopic diagnosis of acute gastric bleeding can be
      problematic and missing diagnoses are not uncommon. However, the causes of
      diagnostic difficulty and the most common locations of bleeding resulting in
      missed diagnosis are not well known. METHODS: To determine the causative factors
      of incomplete study, we analyzed the medical records and performed follow-up on
      64 patients for whom initial emergency endoscopy had failed to identify the sites
      of acute gastric bleeding. The bleeding sites were confirmed by the findings of
      subsequent endoscopic examination or operation in these cases. RESULTS: Excessive
      blood covering the examination field was the most frequent cause of incomplete
      endoscopic study (60/64). Underlying gastric lesions which were later identified
      as sources of gastric bleeding included: 30 gastric ulcers, 9 gastric varices, 6
      acute gastric mucosal lesions, 3 Dieulafoy's lesions, 3 portal hypertensive
      gastropathies, 2 gastric tumors, 1 Mallory-Weiss tear and 2 unidentified bleeding
      sites. Eight patients refused further evaluation. The locations of the bleeding
      sites included: 1 esophagocardiac junction, 8 cardia, 5 fundus, 21 body, 9
      antrum, 7 stoma, 3 diffuse pattern. The 42-day mortality rate of these patients
      was 20%. Of these patients, decompensated liver cirrhosis (8/13) and hepatic
      failure (7/13) were the most common underlying diseases. CONCLUSION: Inadequate
      preparation was the most frequently procedural problem associated with missed
      diagnosis. Lesions located in the body of the stomach were most likely to go
      undiagnosed. Gastric ulcers were the most common type of unidentified bleeding
      ulcer site. Hepatic failure was the most common cause of death. The high
      mortality rate of these patients appeared to be related to underlying diseases
      rather than to the nature of the lesions responsible for gastric bleeding.

PMID- 9260367
TI  - Comparison of clinical efficacy and adverse effects between extended-release
      felodipine and atenolol in patients with mild and moderate essential
      hypertension.
AB  - BACKGROUND: Essential hypertension is a risk factor for cardiovascular disease.
      Atenolol, a cardio-selective beta-blocker, has been shown to be a safe and
      effective antihypertensive agent. The extended-release form of felodipine
      (felodipine ER), a vascular-selective dihydropyridine calcium blocker, is
      extensively used in Caucasians. However, its effectiveness, tolerability and
      adverse side-effect have not been assessed in Chinese populations. METHODS:
      Sitting blood pressure (BP), heart rate, body weight, adverse reaction and serum
      biochemistry were assessed in 70 patients with mild-moderate essential
      hypertension treated either with felodipine ER (37 patients), or atenolol (33
      patients) for 10 weeks. Each patient was prescribed 5 mg of felodipine ER or 50
      mg of atenolol once daily and this daily dosage was doubled to twice daily if
      necessary. RESULTS: Six patients who received felodipine ER and 3 who received
      atenolol withdrew from the treatment because of intolerable side effects. Within
      ten weeks, 81.1% of the patients had responded to a total daily dosage of 5-10 mg
      of felodipine ER and 81.8% to a daily dose of 50-100 mg of atenolol. By the end
      of treatment, the mean BP in the felodipine ER group had decreased from 176/104
      mmHg at baseline to 145/85 mmHg, while the BP in the atenolol group had dropped
      from 173/103 mmHg to 145/84 mmHg (NS between the two groups). Heart rate declined
      in the atenolol group but did not change in patients who received felodipine ER.
      Overall, patients in the felodipine ER group had a higher rate of adverse
      reaction (70.3% vs. 39.4%; p < 0.001), and 16.2% of the patients in the
      felodipine ER group experienced symptoms of hypotension. CONCLUSION: Equivalent
      doses of felodipine ER and atenolol are effective first-line monotherapeutic
      agents for the treatment of mild-moderate essential hypertension.

PMID- 9260368
TI  - Laryngeal tuberculosis: a series of 46 patients.
AB  - BACKGROUND: The incidence of laryngeal tuberculosis is declining after the advent
      of anti-tuberculous drugs. The disease itself is changing according to our
      experience, too. The changing pattern is our interest. METHODS: A series of 46
      cases of laryngeal tuberculosis seen in our institution between 1980 and 1995
      were reviewed retrospectively to assess the various features of the disease.
      RESULTS: The results showed a mean age of 48 years and a sex ratio of 2:1.
      Hoarseness is the most frequent presenting symptom (80%), and sore throat (52%)
      is another important symptom. The frequent locations of lesions are the true
      cords (57%), epiglottis (39%), false cords (35%), arytenoids (24%) and posterior
      commissure (7%). Laryngeal tuberculosis was the most common initial working
      diagnosis before a definite pathological report was completed. In 85% of the
      patients the disease was transmitted by bronchogenic route, and in the others it
      was primary laryngeal tuberculosis. Laryngeal tuberculosis responds well to early
      treatment with anti-tuberculous chemotherapy. CONCLUSION: The clinical
      presentation of laryngeal tuberculosis is changing. It is necessary to detect the
      disease early to prevent the development of severe sequalae or mortality.

PMID- 9260369
TI  - Primary uncemented Osteonics total hip arthroplasty: preliminary results of 2-6
      year follow-up.
AB  - BACKGROUND: Cemented total hip arthroplasty (THA) bears the inherent
      disadvantages of cement complications. A research toward the improvement of
      uncemented prosthesis design continues to evolve. The purpose of this report is
      to present the preliminary results and to identify common problems in uncemented
      THA. METHODS: The results of 402 primary Osteonics total hip prostheses were
      reviewed with an average follow-up period of 3.1 years. The postoperative rating
      according to the modified D' Aubigne & Postel hip score included functional and
      radiographic analysis. RESULTS: The results were rated as good or excellent in
      95% of hips. Stable fixation of the prosthesis was shown in 97% of radiographs.
      The most common zone of focal osteolysis was in the periarticular area.
      CONCLUSION: The clinical results in a 2 to 6 year follow-up was encouraging. A
      relatively high incidence of thigh pain did not correlate with femoral canal
      filling of prosthesis. Periarticular osteolysis is still an unsettled problem in
      uncemented prostheses and needs further investigation.

PMID- 9260370
TI  - Acute toxicities and feasibility of altered fractionated radiotherapy in
      nasopharyngeal carcinoma.
AB  - BACKGROUND: Altered fractionated radiotherapy (AFR) has been used for many years
      in the treatment of cancer. Although AFR therapy improves tumor control, it also
      increases acute radiation toxicities, which may make patients withdraw from
      treatment. Here, we report on the efficacy of AFR in the treatment of
      nasopharyngeal cancer (NPC). METHODS: From September 1993 to October 1994, 68 NPC
      patients received AFR in Chang Gung Memorial Hospital-Linkou. The efficacy of two
      types of AFR were studied: (a) Hyperfractionated radiotherapy (HFT) in which
      irradiation was given twice a day throughout the radiotherapy course with a total
      radiation dose of 81.6 Gy/68 fractions in 7 weeks; and (b) Concomitant boost
      radiotherapy (CBT) in which additional concommitant radiotherapy was administered
      only during the last 2 weeks of the radiotherapy course. The total radiation dose
      of CBT was 72.3 Gy/42 fractions in 6 weeks. Twenty-six patients received HFT and
      42 received CBT. RESULTS: The percentage of grade 3 complications was 73% in CBT
      and 65% in HFT. The mean number of treatment days was 57.1 in HFT (median, 53;
      range 48-63) and 43.9 in CBT (median, 43; range 40-60). No patient withdrew from
      or prolonged the treatment because of acute radiation toxicities. CONCLUSION: Our
      results demonstrated that NPC patients can tolerate HFT and CBT radiotherapy with
      sufficient psychological support. Further randomized trials will be continued in
      our institution.

PMID- 9260371
TI  - A pilot study of seven days of ceftriaxone therapy for children with Salmonella
      enterocolitis.
AB  - BACKGROUND: The most effective therapy for non-typhoid Salmonella enterocolitis
      is still unknown. Traditionally, unless extraintestinal complications are
      present, antimicrobial drugs are not recommended, since earlier trials have shown
      that antibiotics such as ampicillin, chloramphenicol, or co-trimoxazole, do not
      shorten the duration of diarrhea and may even prolong convalescent fecal carriage
      of the bacteria. However, the recently-developed third generation cephalosporin
      ceftriaxone has been used successfully in the treatment of typhoid fever and
      other systemic salmonellosis. A controlled, pilot study was therefore undertaken
      to evaluate the efficacy of intravenous ceftriaxone in the treatment of children
      with non-typhoid Salmonella enterocolitis. METHODS: Fifteen children with
      Salmonella enterocolitis and bacteremia who were eligible for antibiotic therapy
      were given ceftriaxone intravenously for 7 days and 15 children with
      enterocolitis but without bacteremia who were admitted for supportive treatment
      during the study period were selected as the control group. Available stool
      samples collected on days, 7, 14, and 30 after the completion of the drug therapy
      were checked for the presence of the bacteria using polymerase chain reaction
      (PCR) and culture methods. RESULTS: The result showed that the duration of
      diarrhea was not significantly affected by ceftriaxone treatment. However, the
      difference in the rate of clearance of Salmonella from stools, as defined by
      negative stool cultures and PCR, was statistically significant between the two
      groups on posttreatment days 7 and 14. Only one patient given ceftriaxone was
      shown to have recrudescence of the bacteria in feces on day 14. One month after
      therapy, PCR was positive in two of the ten cases tested and one of these two
      experienced a relapse of diarrhea, whereas bacterial carriage was maintained in
      63% of the control patients. CONCLUSION: A prompt eradication of Salmonella in
      feces was observed in most of the patients treated with ceftriaxone in this
      study. If further studies confirm the efficacy of this therapy and the risk of
      inducing drug resistance is minimal, the epidemiologic problem created by
      convalescent fecal bacterial carriage may justify a short-course of ceftriaxone
      therapy for children with Salmonella enterocolitis.

PMID- 9260372
TI  - Home-made endoloops for bullous lung disease: a case report.
AB  - Various surgical techniques for bulla ablation have been used since the
      introduction of video-assisted thoracoscopic surgery. Endoscopic stapler
      resecting (Endo-GIA) is now the most common procedure for bulla ablation. Other
      endoscopic techniques include bulla suturing, clipping, laser ablation and
      electrocauterization. We present here a select report on using a "home-made"
      endoloop on a patient with bullous lung disease. No intraoperative morbidity was
      attributable to the procedure. The operating room time was 110 minutes, and
      ventilator support was given for 18 hours. The chest tube was removed on day 7
      and the patient discharged on the ninth postoperative day uneventfully. The
      patient exhibited subjective improvement in his symptom preceptions during an one
      month follow-up examination. A comparison of pre- and post operative functional
      evaluation showed increase in FEV1 (from 0.45 L to 1.02 L) during 3-month follow
      up. From our experience, thoracoscopic home-made endoloop ligation is a safe and
      cost effective means of volume reduction surgery for bullous emphysema that
      interferes with optimum function of the adjacent lung parenchyma.

PMID- 9260373
TI  - Endoscopic polypectomy of a large inflammatory fibroid polyp of the stomach: a
      case report.
AB  - Gastric inflammatory fibroid polyp (IFP) is a rare benign submucosal tumor. It
      consists of mesenchymal and spindle-shaped cell proliferations with inflammatory
      cell infiltrations. With the widespread use of fiberoptic endoscopy, gastric
      polypoid lesions are being recognized with increasing frequency. Conventionally,
      they have been treated using surgical excision, after which accurate pathological
      diagnosis was obtained. Recently, endoscopic polypectomy has been widely used and
      has shown good results in both diagnosis and treatment of polypoid lesions of the
      stomach. We report a case in which a large symptomatic gastric IFP was
      successfully removed using single-channel endoscopy.

PMID- 9260374
TI  - Castleman's disease: a case report.
AB  - Castleman's disease is a rare, benign disorder most commonly located in the
      mediastinum as a solitary mass. It is a lymphoid tissue disorder characterized by
      lymphoid proliferation. In this paper we describe a case of asymptomatic
      interlobar fissure tumor, localized Castleman's disease, hyaline vascular type,
      in a 30-year-old female. The tumor arose from the interlobar fissure between the
      right middle and lower lobes. Laboratory data revealed hypochromic microcytic
      anemia, similar to that found in iron deficiency, and an elevated erythrocyte
      sedimentation rate. She underwent video-assisted thoracic surgery for excision of
      the tumor. Anemia disappeared two months after surgery. No recurrence of the lung
      tumor was seen 19 months following surgery and she remains well.

PMID- 9260375
TI  - Dislodgment of catheter during arterial cannulation: a case report.
AB  - Invasive blood pressure monitoring is important in medical practice, especially
      for hemodynamic monitoring of the critically ill. Catheter dislodgment is a
      rarely reported complication. We herein report a catheter dislodgment
      complication during the procedure of arterial cannulation.

PMID- 9260376
TI  - Rickets of premature infants induced by calcium deficiency. A case report.
AB  - Rickets of prematurity is not uncommon in neonatal intensive care units.
      Nutritional rickets in childhood is usually caused by vitamin D deficiency, but
      the rickets of prematurity is mainly attributable to calcium and phosphorus
      deficiencies. We present a premature infant with sequelae of necrotizing
      enterocolitis who needed prolonged administration of total parenteral nutrition
      (TPN), and who sustained ricketic fracture. After high calcium-fortified TPN
      supplementation the fracture healed well, and serum alkaline phosphatase dropped.
      This finding shows (1) serum calcium and phosphorus levels are of predictive
      value regarding rickets, (2) regular follow-ups of alkaline phosphatase levels
      combined with radiography in high-risk groups of premature infants are good tools
      for monitoring rickets, and (3) prolonged TPN administration needs to contain
      higher calcium and phosphorus concentrations in prematurity than in childhood.

PMID- 9260377
TI  - Chronic granulomatous disease: a case report.
AB  - Chronic granulomatous disease is an uncommon inherited disease with presentations
      of frequent pyogenic and fungal infections. In this disease, the phagocytes
      ingest pathogens, but the ingested microorganisms can not be killed because the
      cells lack the ability to convert oxygen into superoxide using the enzyme known
      as NADPH oxidase. We report on a patient who had experienced frequent
      lymphadenopathy and bacterial infections since childhood. In addition to his
      history of repeated bacterial infections, diagnosis was also based on abnormal
      findings in immunologic tests including the nitroblue tetrazolium test assay,
      analysis of chemiluminescence and detection of hydrogen peroxide using flow
      cytometry. He received prophylactic treatment with antibiotics, and the condition
      remained stable during a six-month follow-up period.

PMID- 9260378
TI  - Implementing instructional technology. Strategies for success.
AB  - This article describes strategies for the integration of computer technology in a
      university-based school of nursing. Faculty concerns related to use of computer
      technology were assessed in a previous study. A series of computer technology and
      literacy workshops were developed based on this assessment. Computer use
      increased and faculty concerns about technology decreased after workshop
      participation. Other strategies to integrate computer technology include
      developing an informatics committee and planning and initiating a technology
      infrastructure consisting of hardware and software resources, and a local area
      network. Strategic planning was initiated placing increasing emphasis on
      curriculum integration of computer technology and nursing informatics.

PMID- 9260379
TI  - The barriers and benefits of nursing information systems.
AB  - Nursing informatics is a growing field with many opportunities for nursing
      involvement. Because nurses are involved increasingly in the design,
      installation, and use of nursing information systems (NIS) it is important that
      they are aware of the barriers to and benefits of nursing information systems.
      This article describes the evolution of nursing information systems and the
      design goals for current systems. The lack of a unified nursing language and
      individual and organizational factors such as characteristics of the nurse, the
      unit, the administrative philosophy, and workload issues are discussed as
      barriers to NIS development. Increased nurse involvement, education, research,
      and recognition of the benefits of computerization are suggested to overcome the
      barriers. A review of the literature provides the reader with evidence of
      improved efficiency, patient safety and satisfaction, and ability to measure
      quality as benefits of NIS. Areas for further research are identified: outcomes
      measurement using NIS, decision support and expert systems, point-of-care
      documentation, interagency and interdisciplinary communication, and further work
      on individual and organizational factors.

PMID- 9260380
TI  - Computers in home care. Application of change theory.
AB  - Home health care is the fastest growing sector in providing health care in the
      United States (US Commerce Department, 1993). Among the reasons for this
      exceptional growth rate are several factors, including an aging population,
      patient preference for care provided in their own homes, earlier discharge from
      acute care settings, and reimbursement sources demanding that health care
      providers reduce costs while expanding patient services in a wider variety
      settings. As a result, home health care agencies are under increasing pressure to
      provide efficient, high-quality, cost-effective nursing services to growing
      numbers of patients. In an effort to maximize productivity and efficiency while
      reducing costs in home health care, one strategy has been to computerize the
      nursing records. However, there has been little or no research in the literature
      on the nursing applications of computer technology in home care settings. Based
      on Lippitt's Theory of Planned Change as the theoretical model, this case study
      examines the author's experience as a consultant to the Nursing Department of a
      home health care agency in automating their nursing records. Included in the
      discussion are an analysis of the costs and benefits derived by the agency in
      phases of planned change, evaluation of the process, and recommendations for the
      future.

PMID- 9260382
TI  - Protecting our most precious resource.

PMID- 9260381
TI  - A comparison of nursing activities associated with manual and automated
      documentation in an Australian intensive care unit.
AB  - This article describes a comparative study that examined the frequencies of
      nursing activities, when using a clinical information system (CIS) and a paper
      based documentation system in an Australian intensive care unit. The study unit
      had half the beds equipped with a CIS, and the remaining beds used paper
      documentation. Work sampling methodology was used to observe nurses working with
      both systems. Though there were differences for all activities between the
      environments and the directions of the differences were logical, none were
      statistically significant using a chi-square test (P = .11-0.65), probably
      because of the small sample size. This study established that work sampling
      methodology using a random timer is a valid and relatively easy method to capture
      work activity in the clinical area. Although this article does not provide
      definitive information regarding the benefits of a CIS over manual documentation,
      a number of important methodological issues are discussed, including the study
      design, procedure, use of dedicated observers, and the distinction between basic
      versus fully optioned systems. Future research should evaluate the efficiency,
      impact on patient outcomes and nursing practice, and cost effectiveness of fully
      optioned systems.

PMID- 9260383
TI  - Strengthening our child abuse response system.
AB  - Medical professionals are often the people who see children first, whether in the
      safety of a private office, clinic or an emergency room. Your ability to
      recognize and understand the symptoms of child abuse and neglect, your readiness
      to report findings to the report line and your availability to provide expert
      witness testimony are critical to the effectiveness of the child abuse response
      system in Delaware.

PMID- 9260384
TI  - Physical abuse of children: an update.
AB  - Now, more than ever, physicians must be willing to suspect child abuse and report
      their concerns. New information from the past decade warns us that reports of
      violence against children continue to increase. We are learning that MRI imaging
      of the head may, in some cases, help date subdural hematomas, but long-term
      developmental follow-up studies of "shaken" infants are lacking. Intentional
      thoracic and abdominal injuries carry a high mortality. Finally, new information
      in the field of child abuse-in particular, physical abuse-is slow to come. Lack
      of funding for basic medical child abuse research and lack of trained researchers
      in the field are the two most important barriers. Preventive intervention at the
      community and family level needs to be supported by both the pediatrician and the
      local and national government leaders. As the U.S. Advisory Board on Child Abuse
      and Neglect says, "We need to make it as easy for parents to pick up the
      telephone and get help before they abuse their child as it is now for their
      neighbor or physician to pick up the telephone and report them after it has
      happened." Child health practitioners may be in the best position to implement
      such a policy.

PMID- 9260385
TI  - The diagnosis of inflicted injury in infants and young children.

PMID- 9260386
TI  - Minimum criteria for reporting child abuse from health care settings.
AB  - We evaluated how consistently clinicians of two hospitals reported child abuse
      and neglect, and the utility of specific, operational criteria for assessing
      hospital clinicians' compliance with the child abuse reporting laws. To evaluate
      clinicians' compliance, we audited the medical records of 85 children who had
      been reported to a child protective service (CPS) agency by clinicians at either
      of two hospitals and who had been seen at that hospital at least once before the
      index report of abuse. The time elapsed from first hospital visit to index abuse
      report among the 85 children averaged 4.3 years. In the children's records, we
      identified 28 earlier reports to the CPS agency and four episodes that met
      criteria we developed but that had not been reported. Thus, application of
      specific criteria resulted in the finding that 28 (88 percent) of 32 suspected
      abuse episodes were actually reported to the CPS agency (95 percent confidence
      interval: 76 to 99 percent). In a second phase of the study, we compared the
      content of 45 reported episodes of child abuse (4) index reports and four earlier
      reports) to the criteria in order to evaluate their utility. Thirty-five episodes
      (78 percent) met one of the criteria. Review of the remaining 10 episodes led to
      the development of one new criterion. We conclude that, although it has been
      estimated that hospital personnel nationwide report to CPS agencies only 69
      percent of the child abuse cases they identify, clinicians at the hospitals we
      studied reported 88 percent of documented episodes of suspected abuse. We also
      conclude that specific, operational criteria can help in the assessment of
      hospital clinicians' compliance with their obligation to report child abuse and
      neglect.

PMID- 9260387
TI  - Shaken baby syndrome: inflicted cerebral trauma. Committee on Child Abuse and
      Neglect, 1993-1994.
AB  - Physical abuse is the leading cause of serious head injury in infants. While
      physical abuse has in the past been a diagnosis of exclusion, data regarding the
      nature and frequency of head trauma consistently support a medical presumption of
      child abuse when a child younger than one year of age has intracranial injury.
      Shaken baby syndrome is a serious form of child maltreatment, most often
      involving infants younger than six months of age. It occurs commonly, yet it is
      frequently overlooked in its most subtle form and underdiagnosed in its most
      serious expression. Caretakers may misrepresent or have no knowledge of the cause
      of the brain injury. There is often an absence of externally visible injuries.
      Given the initial difficulty of identifying a shaken infant and the variability
      of the syndrome itself, the physician must be extremely vigilant regarding any
      brain trauma in infants and be familiar with the radiologic and clinical findings
      that support the diagnosis of the shaken baby syndrome.

PMID- 9260388
TI  - Distinguishing sudden infant death syndrome from child abuse fatalities.
      Committee on Child Abuse and Neglect, 1993-1994.
AB  - Public and professional awareness of sudden infant death syndrome (SIDS) has
      increased in the 28 years since the establishment of the National Sudden Infant
      Death Foundation, now called the National SIDS Alliance.' Similarly, awareness of
      child abuse has increased in the 30 years since the publication of the first
      article on the battered child. In the majority of cases, when an infant younger
      than one year dies suddenly and unexpectedly, the cause is SIDS. Sudden infant
      death syndrome is for more common than infanticide. In a few difficult cases,
      legitimate investigations for possible child abuse have resulted in an
      insensitive approach to grieving parents or caretakers. This statement provides
      professionals with information and guidelines to avoid distressing or
      stigmatizing families of SIDS victims while allowing accumulation of appropriate
      evidence in the uncommon case of death by infanticide.

PMID- 9260389
TI  - Spinal epidural hematoma and ankylosing spondylitis.
AB  - Spinal epidural hematoma is an unusual condition requiring urgent neurosurgical
      intervention. Imaging plays an important role in the preoperative work-up.
      Although MR imaging is the examination of choice, a myelogram and CT myelogram
      are often performed in an emergency situation. The association with ankylosing
      spondylitis has been described and is considered a risk factor for developing a
      hematoma.

PMID- 9260390
TI  - Mesenteric panniculitis.
AB  - Mesenteric panniculitis is a non-neoplastic inflammatory process affecting the
      adipose tissue of the mesentery. It is an extremely rare disease. We report the
      case of a 30-year-old man with mesenteric panniculitis and describe the
      radiologic findings.

PMID- 9260391
TI  - Hepatic cystic mass with a daughter cyst: a feature of mucinous cystadenoma.
AB  - The authors describe the US and CT features of a hepatic mucinous cystadenoma
      presenting as a hepatic cystic mass with a daughter cyst in a 50-year-old female
      patient. The contribution of the current imaging modalities is analyzed and a
      review of the literature is presented.

PMID- 9260392
TI  - Pancreatic involvement in systemic sarcoidosis: CT findings.
AB  - Sarcoidosis of the pancreas is a rare entity. We report on the computed
      tomographic demonstration of multifocal pancreatic involvement in a patient with
      systemic sarcoidosis.

PMID- 9260393
TI  - The Holt-Oram syndrome: radiological approach.
AB  - The clinical and radiological findings in a female child with Holt-Oram syndrome
      are reported. The most important features are cardiac anomalies associated with
      typical anomalies of the skeleton of the forearms.

PMID- 9260394
TI  - [Preliminary results of a screening programme by mobile units in the province of
      Liege].
AB  - The goal of the mass screening of breast cancer undertaken under the authority of
      the Province of Liege is to focus the action on rural communities. For this
      reason, mobile vans equipped with X-Ray dedicated units are used. The main
      difficulty of this programme is to reach a massive participation of the
      population. It varies up to now from 45% to 20% in the different visited
      villages. During the 42 first months of functioning, 16,207 mammographies were
      carried out in women aged from 40 to 69; 69 cancers were discovered in apparently
      healthy women plus 10 cases of epithelial hyperplasia with atypias. These first
      results are quite encouraging. The main task of this continuing programme will be
      to reach a better participation of the population.

PMID- 9260395
TI  - Ultrasound of the elbow.
AB  - Ultrasound examination of the elbow should be performed in a comparative way,
      exploring joint spaces and fossas. Ultrasound is the method of choice for the
      detection of joint fluid and loose bodies. Tendinitis and microfissures can be
      demonstrated in case of tennis and golfer elbow. On the posterior aspect of the
      elbow, ultrasound shows the different types of bursitis, and allows evaluation of
      the ulnar nerve in cases of impingement.

PMID- 9260396
TI  - Low back pain and nuclear medicine.
AB  - Low back pain (LBP) is a major cause of disability in many patients during some
      time of their lives. In this article the role of nuclear medicine, and more in
      particular the role of single photon emission tomography (SPECT), in the
      investigation of LBP is discussed by reviewing the literature. Because of the
      improved anatomical localization of lesions in the vertebral body when up-to-date
      SPECT is used, this technique is a powerful imaging modality in patients with
      LBP. Bone scintigraphy therefore can contribute significantly in the diagnosis of
      patients with LBP. In cases where conventional radiological techniques fail to
      elucidate the cause of LBP performing a bone scintigraphy with SPECT should
      strongly be recommended.

PMID- 9260397
TI  - Picture archiving and communication system (PACS): medical perspectives.
AB  - PACS represents the natural evolution from the digital new modalities (US, CT,
      MRI,...) to a global digital environment, where the film based activities are
      progressively replaced by their digital counterpart. The advantages of the
      technique, as well as the drawbacks of the first implementations, are described.
      The "second generation" PACS concept is presented (modular architecture,
      progressive implementation, multivendor environment, integration with the
      Hospital Information System, standardization,...). As "case study", the example
      of the A.Z.-V.U.B. Hospital Implementation is described.

PMID- 9260398
TI  - Magnetic resonance imaging of cardiac and pericardial disease.
AB  - To date, most application of cardiovascular MRI relate to the evaluation of major
      vessels rather than the heart itself. However, MRI plays a major role in the
      evaluation of specific types of cardiovascular pathology, namely intracardiac and
      paracardiac masses, pericardial disease, and congenital heart disease. Because
      the visualization of cardiovascular anatomy with MR is non-invasive and permits
      three-dimensional analysis, it is clear that MRI will have a growing and
      significant impact over the next years. We will review some of the technical
      aspects of cardiac MRI and will describe the current and potential clinical and
      investigative applications of this new methodology.

PMID- 9260399
TI  - Magnetic resonance imaging of thoracic vascular disease (congenital diseases
      excluded).
AB  - To date, most applications of cardiovascular MRI relate to the evaluation of
      major vessels. We review the currently established indications for thoracic
      vascular MRI and will touch on the advances that are likely to change the way we
      examine great thoracic vessels.

PMID- 9260400
TI  - Prevalence and etiology of intestinal parasites in Lebanon.
AB  - As there are no studies done on the prevalence of intestinal parasites in Lebanon
      since 1967, this study was undertaken to reveal the current patterns of
      intestinal parasitic infestations in Lebanese patients from two geographic
      regions: Beirut and Tripoli. Analysis was based on 33,253 stool specimens
      examined at the American University of Beirut Medical Center (AUH) and 11,611
      specimens examined at the Islamic Hospital (IH) in Tripoli over five and three
      years, respectively. The prevalence of intestinal parasites at AUH and IH were
      8.47% and 45.35%, respectively (overall 18%). The prevalence in males vs females
      was almost the same; being 8.23% vs 8.74%, and 44.67% vs 45.88%, at AUH and IH,
      respectively. Multiple infections were noted in 8.8% and 3.5% of stool specimens
      at AUH and IH, respectively. Although 18 different types of parasites were
      encountered, the most common pathogenic parasites found at AUH vs IH were:
      Giardia lamblia (20.7% vs 10.5% of parasites found), Entamoeba histolytica
      (19.41% vs 1.25%), Taenia spp. (6.03% vs 4.08%) and Ascaris lumbricoides (2.09%
      vs 46.97%). The overall yearly or monthly prevalence of parasites recovered from
      both hospitals did not show clear seasonal patterns. Compared to developed
      countries, Lebanon still suffers from a high prevalence and a wide spectrum of
      intestinal parasites.

PMID- 9260401
TI  - New trends: preperitoneal laparoscopic inguinal hernia repair.
AB  - Laparoscopic herniorrhaphy is a relatively new and successful surgical technique
      and follow-up studies are beginning to provide short- and middle-term results. In
      this article, the authors discuss their experience and technique with the
      preperitoneal laparoscopic inguinal hernia repair between the years 1993 and 1995
      during which they accomplished 30 herniorrhaphies on 25 patients with one
      recurrence and four postoperative neuralgias.

PMID- 9260402
TI  - Estimation of cancer incidence in Lebanon.
AB  - Cancer incidence rate is an important indicator for policymakers seeking to
      establish a National Cancer Control Program in Lebanon. This rate is difficult to
      assess, however, in view of the absence of national health and vital statistics.
      Fragmentary data from 1984 were used to estimate the annual cancer case-load at
      3,500 cases. For an estimated population of 3.29 million, this case-load yields
      an incidence rate of 106 per 100,000. This low rate has not varied much since the
      mid-60s, and is nearer to that of developing than of developed nations. Cancer
      incidence may however increase in the coming few years with the aging of the
      population, and increasing urban pollution, smoking and adverse diet changing.

PMID- 9260403
TI  - Analgesics and the kidney: recommendations of the National Kidney Foundation for
      the use of analgesics.

PMID- 9260404
TI  - The environment and the eye. Topics of ophthalmic toxicology.

PMID- 9260405
TI  - Current concepts in plastic surgery of the nose.

PMID- 9260406
TI  - Sense of self in children with cancer and in childhood cancer survivors: a
      critical review.
AB  - The experience of childhood cancer is reported to be stressful for children with
      cancer and their families. Of special concern with respect to the consequences of
      cancer stressors is the issue of how cancer affects the child's sense of self. It
      has been suggested that the child's sense of self may be altered or potentially
      harmed by the effect of cancer and its treatment. Changes in the child's sense of
      self, in turn, may affect the child's quality of life. The purpose of this
      article is to examine what is known about the sense of self in children with
      cancer and in childhood cancer survivors. Additionally, conceptual and
      methodological concerns related to studying the sense of self in the pediatric
      oncology population are discussed. These include (1) conceptual blurring related
      to how the self is defined; (2) minimal theoretical grounding specific to
      understanding the self; and (3) limited research approaches to studying the self.
      Recommendations for research and practice that will lead to an increased
      understanding of the sense of self in this patient population are presented.

PMID- 9260407
TI  - Parental reports of changes and challenges that result from parenting a child
      with cancer.
AB  - Cancer in a child leads to a more stressful family life, including problems in
      adjusting to the situation. The aim of this study was to identify the parents'
      experience of problems related to their child's/adolescent's cancer and the
      effect of those problems on the parents' life situation. Swedish parents of 15
      children and adolescents with varying diagnoses and treatments were interviewed
      using qualitative methods. The interview data were analyzed by two researchers
      using a constant comparative method. The results included eight categories of
      problems influencing the parents' life situation: watching our child suffer;
      being governed by our child's disease; behaving differently as a family member;
      experiencing strong feelings and reactions; trying to cope; dealing with the
      reactions of others; finding support from others; and evaluating the quality of
      care. Seven of these categories validate previously reported parental concerns,
      but one, evaluating the quality of care, has not been previously reported. Study
      findings can be used to help sensitize health care personnel to the problems
      experienced by parents of children and adolescents with cancer and the capacity
      parents have to deal with the problems.

PMID- 9260408
TI  - Assessment and management of chemotherapy-induced mucositis in children.
AB  - Oral mucositis is one of the most common side effects of cancer treatment. The
      oral mucosa is comprised of membranes of a high mitotic index with rapid
      epithelial turnover and maturation rates. This causes the mucosa to be vulnerable
      to the adverse effects of chemotherapy. Chemotherapy alters the integrity of the
      mucosa, the microbial flora which normally inhabit the oral cavity, salivary
      quantity and composition, as well as the epithelial maturation. As a result, the
      child receiving chemotherapy may experience significant pain, dysphagia,
      alteration in nutritional status, and risk of infection. Severe mucositis can
      also delay therapy that may compromise the child's treatment and chance for cure.
      Not all chemotherapy-induced mucositis can be prevented. However, with proper
      management, the severity and duration of oral complications can be minimized.

PMID- 9260409
TI  - Development of two instruments examining stress and adjustment in children with
      cancer.
AB  - The childhood cancer literature provides limited understanding of the school-age
      child's perception of cancer stressors and factors that contribute to adjustment
      in the midst of these stressors. This study evaluated the reliability and
      validity of two questionnaires: the Childhood Cancer Stressors Inventory (CCSI)
      and the Children's Adjustment to Cancer Index (CACI). The following steps were
      involved in the instrument development process: item development, face and
      content validation, internal consistency reliability, and construct validity.
      Questions for both instruments were developed from the literature and experience
      of the principal investigator. A panel of five expert pediatric oncology nurses
      was asked to evaluate the content validity of both instruments. All the experts
      rated every item a 4-5 using the content validity index, indicating that each
      item measured the concept addressed by the scale. Seventy-five children with
      cancer were asked to complete the two questionnaires and parents completed a
      demographic data sheet that included eight questions about the child's school
      attendance, performance, number of friends, and activities. Children were 7 to 13
      years of age; 64% were diagnosed with a leukemia/ lymphoma, and 36% had a solid
      tumor. Internal coefficient reliability for the total CCSI was .82, and .91 for
      the CACI. The CCSI correlated negatively with the adjustment scale (r = -.63, P =
      000). The number of days missed from school correlated positively with the CCSI
      and negatively with the CACI. Children who missed more school perceived more
      cancer stressors and had a lower adjustment rating. Children with lower
      adjustment ratings on the CACI also had fewer friends (t = 3.4(72), P = .001).
      Scores on both instruments demonstrated expected relationships with measures
      hypothesized to covary with the dimensions assessed by the new instruments.
      Adjustment issues for children with cancer have been difficult to assess because
      of the lack of appropriate instruments. These study findings indicate that the
      two new instruments can help to measure the child's perceptions of the cancer
      experience.

PMID- 9260410
TI  - APON merges onto the information superhighway.

PMID- 9260411
TI  - Do it or lose it.

PMID- 9260412
TI  - Need for TMJ surgery.

PMID- 9260413
TI  - Resin restorations.

PMID- 9260414
TI  - Soap and home care.

PMID- 9260415
TI  - Endodontic therapy.

PMID- 9260416
TI  - Nitrous oxide safety.

PMID- 9260417
TI  - Dentistry for the 21st century? Erbium:YAG laser for teeth.
AB  - The first dental laser for use in cutting human teeth in vivo was cleared by the
      Food and Drug Administration for marketing in the United States. The authors
      explored, in summary form, the data provided to the FDA for the clinical use of
      the erbium:yttrium-aluminum-garnet, or Er:YAG, laser. The authors concluded that
      using the Er:YAG laser to treat dental hard tissue is both safe and effective for
      caries removal, cavity preparation and enamel etching.

PMID- 9260418
TI  - Clinical evaluation of compomer in primary teeth: 1-year results.
AB  - The clinical performance of the compomer Dyract (L.D. Caulk, Dentsply) was
      evaluated and compared with that of the hybrid composite resin Prisma TPH (L.D.
      Caulk, Dentsply) in restorations of 60 bilateral matched pairs of primary teeth.
      After 1 year, the overall failure rate for both restorative materials was 1.7
      percent. There were no statistically significant differences in recurrence of
      caries, color matching, marginal integrity or anatomic form. The only
      statistically significant differences were in marginal discoloration and wear,
      where the compomer was inferior to the hybrid composite resin. The authors
      conclude that compomer is a suitable alternative to amalgam for restoring primary
      teeth.

PMID- 9260419
TI  - Pulpal response to cavity preparation by an erbium, chromium:YSGG laser-powered
      hydrokinetic system.
AB  - The near red-pulsed erbium, chromium:yttrium-scandium-gallium-garnet laser
      hydrokinetic system, or Er,Cr:YSGG laser HKS, is effective in cutting dental hard
      tissues. In this longitudinal study, the authors studied the continuously
      erupting open-apex incisors of New Zealand albino rabbits and the constricted
      apex teeth of beagles to determine the effects of HKS-produced lesions at various
      energy levels and of preparations produced by a tapered fissure bur on dental
      pulp. No pulpal inflammatory responses could be identified either immediately or
      30 days after surgery in HKS preparations that removed enamel and dentin without
      pulp exposure.

PMID- 9260420
TI  - The hypertensive dental patient.
AB  - The dental team plays an integral role in safeguarding the general health of
      patients. Dental health care workers should be able to recognize risk factors
      associated with hypertension and counsel patients in an effort to reduce those
      that are present. In addition, dental professionals should recognize how these
      risk factors and associated hypertension affect the provision of dental care.
      This article reviews recent findings and therapies for hypertension, evaluates
      historically accepted but unsupported anecdotal information on the dental
      management of hypertensive patients and proposes guidelines for the dental
      management of these patients.

PMID- 9260421
TI  - Using the international normalized ratio to standardize prothrombin time.
AB  - The international normalized ratio, or INR, was introduced in 1983 by the World
      Health Organization, or WHO, Committee on Biological Standards to more accurately
      assess patients receiving anticoagulation therapy. The INR mandates the universal
      standardization of prothrombin time. This article describes the method used to
      calculate INR, as well as its clinical relevance to the practice of dentistry.

PMID- 9260422
TI  - The effect of cementing procedures on retention of prefabricated metal posts.
AB  - Twelve prefabricated posts were cemented in extracted teeth with zinc phosphate
      cement, 14 with resin cement after the canals were acid etched and 14 with zinc
      phosphate cement after acid etching. After thermocycling, specimens were
      subjected to a straight-line tensile force. The posts cemented with resin cement
      had significantly higher tensile strength than those cemented with the two zinc
      phosphate cement treatments.

PMID- 9260423
TI  - Manifestations and treatment of xerostomia and associated oral effects secondary
      to head and neck radiation therapy.
AB  - Xerostomia is one of the most common side effects of head and neck radiation
      therapy. Other oral effects are mucositis and radiation caries. Because
      xerostomia resulting from radiation therapy may be of a more permanent nature
      than xerostomia resulting from other causes, treatment is typically more
      extensive. Numerous regimens treat symptoms of xerostomia and associated caries
      and mucositis. Among them is the daily application of a fluoride gel, recommended
      to prevent or minimize dental caries. For patients with severe, chronic
      xerostomia who have some residual salivary tissue, the use of a sialagogue can
      promote an increased flow of saliva and treat the symptoms.

PMID- 9260425
TI  - An alternative procedure for completely reduced mandibular ridges.

PMID- 9260424
TI  - Postexposure chemoprophylaxis for occupational exposure to HIV in the dental
      office.
AB  - Occupational exposure to HIV continues to be a concern for health care workers.
      Preventing exposure through the use of universal precautions is the primary means
      of protection. New Public Health Service interagency work group recommendations
      for postexposure chemoprophylaxis provide information to help manage occupational
      exposure to HIV.

PMID- 9260426
TI  - A maxillary anterior bite plane: a new design.

PMID- 9260428
TI  - Successful associateship agreements.
AB  - When evaluating potential associateship agreements, dentists need to recognize
      and understand how status, noncompete clauses, scheduling and compensation affect
      the strength of an associateship agreement. Dentists should not enter an
      associateship agreement without fully understanding the agreement and its
      obligations or without the help of an accountant and an attorney.

PMID- 9260427
TI  - Prevention of bacterial endocarditis: recommendations by the American Heart
      Association.
AB  - OBJECTIVE: To update recommendations issued by the American Heart Association
      last published in 1990 for the prevention of bacterial endocarditis in
      individuals at risk for this disease. PARTICIPANTS: An ad hoc writing group
      appointed by the American Heart Association for their expertise in endocarditis
      and treatment with liaison members representing the American Dental Association,
      the infectious Diseases Society of America, the American Academy of Pediatrics
      and the American Society for Gastrointestinal Endoscopy. EVIDENCE: The
      recommendations in this article reflect analyses of relevant literature regarding
      procedure-related endocarditis, in vitro susceptibility data of pathogens causing
      endocarditis, results of prophylactic studies in animal models of endocarditis
      and retrospective analyses of human endocarditis cases in terms of antibiotic
      prophylaxis usage patterns and apparent prophylaxis failures. MEDLINE database
      searches from 1936 through 1996 were done using root words endocarditis,
      bacteremia and antibiotic prophylaxis. Recommendations in this document fall into
      evidence level III of the U.S. Preventive Services Task Force categories of
      evidence. CONSENSUS PROCESS: The recommendations were formulated by the writing
      group after specific therapeutic regimens were discussed. The consensus statement
      was subsequently reviewed by outside experts not affiliated with the writing
      group and by the Science Advisory and Coordinating Committee of the American
      Heart Association. These guidelines are meant to aid practitioners but are not
      intended as the standard of care or as a substitute for clinical judgment.
      CONCLUSIONS: Major changes in the updated recommendations include the following:
      (1) emphasis that most cases of endocarditis are not attributable to an invasive
      procedure; (2) cardiac conditions are stratified into high-, moderate- and
      negligible-risk categories based on potential outcome if endocarditis develops;
      (3) procedures that may cause bacteremia and for which prophylaxis is recommended
      are more clearly specified; (4) an algorithm was developed to more clearly define
      when prophylaxis is recommended for patients with mitral valve prolapse; (5) for
      oral or dental procedures the initial amoxicillin dose is reduced to 2 g, a
      follow-up antibiotic dose is no longer recommended, erythromycin is no longer
      recommended for penicillin-allergic individuals, but clindamycin and other
      alternatives are offered.

PMID- 9260429
TI  - Benefits and risks of medications: challenges for the 21st century.

PMID- 9260430
TI  - Cementing porcelain-fused-to-metal crowns.

PMID- 9260431
TI  - New remedies for 'without-cause' terminations.

PMID- 9260432
TI  - Early diagnosis of colorectal conditions: a risk management and quality of care
      approach.

PMID- 9260433
TI  - Women at risk: papanicolaou smear screening in Florida.
AB  - In the South, especially Appalachia, the incidence of invasive cervical cancer
      has remained high relative to the rest of the United States. Populous Florida now
      stands third among states by incidence and fifth from last in Pap screening.
      During the 1994 survey, 2,059 Florida women chosen as a multi-stage cluster
      sample were interviewed concerning their use of screening Pap smears. Never
      participation in screening percentages were significantly higher in Hispanic
      women (14.7%), those sharing household incomes of less than $10,000 (13.2%), and
      women limited to a high school education (10.7%), but not among respondents older
      than 64 years of age (8.7%). Despite continued annual physician contact by most,
      yearly Pap smears fell to only 57.0% among women aged 55-64 years. It is
      important that physicians target these women and use any appropriate clinical
      contact to educate them about risk factors for cervical cancer while encouraging
      regular, continued use of this life-saving test.

PMID- 9260434
TI  - Breaking the cycle: lidocaine therapy for habit cough.
AB  - Habit or psychogenic cough is a common problem of unknown etiology with a variety
      of suggested therapies. A postulated mechanism is a cough which causes vibration
      of the airway walls, irritation and more cough. Nebulized lidocaine breaks this
      cycle and allows control and resolution of the cough.

PMID- 9260435
TI  - Cesarean deliveries in Florida: current trends and related factors.

PMID- 9260436
TI  - A novel, simplified and cost effective protocol for superovulation and
      intrauterine insemination.
AB  - OBJECTIVE: To determine the efficacy and cost of a simplified superovulation
      regimen compared with traditional control ovarian hyperstimulation with
      gonadotropins (HMG). STUDY DESIGN: This was a retrospective study in a university
      referral center with 99 infertile couples undergoing 225 treatment cycles. The
      outcome was compared to outcomes of previously published studies. The simplified
      superovulation regimen included clomiphene citrate 100 mg on cycle days 5 through
      9 and HMG 75 IU on cycle days 5, 7, 9, and 11, with estradiol and ultrasound
      monitoring on day 13. If adequate follicular maturity was documented, HCG 10,000
      IU was administered, followed by intrauterine insemination 40 hours later.
      RESULTS: Fecundity rates were assessed by life table analysis. Average cycle
      fecundity was 8%, with a cumulative rate of 29% over 4 cycles, compared to 10%
      monthly fecundity with HMG/IUI and background rates of 1 to 3%. Costs averaged
      $662 per cycle compared to $1,854 with HMG/IUI. CONCLUSION: A simplified protocol
      of CC/HMG/ IUI is almost as effective as HMG/IUI and costs only one-third as
      much.

PMID- 9260437
TI  - What can EEG-video monitoring do for you and your patients?
AB  - Epilepsy is a common condition. In most cases, treatment with medications is
      satisfactory. When antiepileptic drugs fail to control the seizures, further
      evaluation may be warranted. EEG-video monitoring can allow a definitive
      diagnosis of epileptic seizures to be made by differentiating epileptic events
      from paroxysmal symptoms that can be mistaken for seizures (i.e.,
      pseudoseizures). In addition, it usually allows one to accurately diagnose the
      seizure type, facilitating selection of the best possible treatment.
      Occasionally, surgery may be a therapeutic option in patients with intractable
      seizures.

PMID- 9260438
TI  - Paternal exposures and the question of birth defects.
AB  - Compared to maternal exposures, little attention has been paid to the possibility
      of paternally induced adverse effects on fetal development. There is increasing
      concern, however, about the potential for male-mediated developmental toxicity
      brought about by exposure to teratogenic agents. This is evidenced by the number
      of calls regarding paternal exposures that are received by teratogen information
      services. In this paper, we report the experience of the state of Florida's
      Teratogen Information Services regarding questions asked about paternal
      exposures, and briefly review what is known about the risk of paternal exposure
      to the 10 agents which are most frequently queried.

PMID- 9260439
TI  - Thirty years of transplantation: 2000 kidney transplants at the University of
      Florida.

PMID- 9260440
TI  - Neuropsychologic functioning in autism: profile of a complex information
      processing disorder.
AB  - Neurobehavioral theories of autism have hypothesized core deficits in sensory
      input or perception, basic attentional abilities or generalized attention to
      extrapersonal space, anterograde memory, auditory information processing, higher
      order memory abilities, conceptual reasoning abilities, executive function,
      control mechanisms of attention, and higher order abilities across domains. A
      neuropsychologic battery designed to investigate these hypotheses was
      administered to 33 rigorously diagnosed autistic individuals with IQ scores
      greater than 80, and 33 individually matched normal controls. Stepwise
      discriminant function was used to define the profile of neuropsychologic
      functioning across domains. The neuropsychologic profile in these autistic
      individuals was defined by impairments in skilled motor, complex memory, complex
      language, and reasoning domains, and by intact or superior performance in the
      attention, simple memory, simple language, and visual-spatial domains. This
      profile is not consistent with mental retardation or with a general deficit
      syndrome, but rather with a selective impairment in complex information
      processing that does not involve visual-spatial processing. This profile is not
      consistent with a single primary deficit, but with a multiple primary deficit
      model in which the deficit pattern within and across domains is reflective of the
      complexity of the information processing demands. This neuropsychologic profile
      is furthermore consistent with the neurophysiologic characterization of autism as
      a late information processing disorder with sparing of early information
      processing.

PMID- 9260441
TI  - The effect of dementia risk factors on comparative and diagnostic selective
      reminding norms.
AB  - Robust comparative and diagnostic norms for the elderly are provided for the
      Selective Reminding Test (Buschke, 1973). Correcting for factors such as age and
      education level are appropriate for comparative norms, which are intended for
      ranking individuals with respect to their age and education matched peers.
      However, because age and education are both risk factors for dementia, correcting
      for these factors decreases test sensitivity for detecting dementia. Age- and
      education-corrected Selective Reminding scores have a sensitivity for detecting
      dementia that is 28% lower than uncorrected scores. Using information about age
      in combination with memory scores provided optimal discrimination of dementia. It
      is concluded that statistically removing the contribution of dementia risk
      factors from memory test scores can severely decrease discriminative validity for
      detecting dementia in the elderly.

PMID- 9260442
TI  - The effect of level of processing on perceptual and conceptual priming: control
      versus closed-head-injured patients.
AB  - Twenty-four closed-head-injured (CHI) and 24 control participants studied two
      word lists under shallow (i.e., nonsemantic) and deep (i.e., semantic) encoding
      conditions. They were then tested on free recall, perceptual priming (i.e.,
      perceptual partial word identification) and conceptual priming (i.e., category
      production) tasks. Previous findings have demonstrated that memory in CHI is
      characterized by inefficient conceptual processing of information. It was thus
      hypothesized that the CHI participants would perform more poorly than the control
      participants on the explicit and on the conceptual priming tasks. On these tasks
      the CHI group was expected to benefit to a lesser degree from prior deep
      encoding, as compared to controls. The groups were not expected to significantly
      differ from each other on the perceptual priming task. Prior deep encoding was
      not expected to improve the perceptual priming performance of either group. All
      findings were as predicted, with the exception that a significant effect was not
      found between groups for deep encoding in the conceptual priming task. The
      results are discussed (1) in terms of their theoretical contribution in further
      validating the dissociation between perceptual and conceptual priming; and (2) in
      terms of the contribution in differentiating between amnesic and CHI patients.
      Conceptual priming is preserved in amnesics but not in CHI patients.

PMID- 9260443
TI  - An examination of the nature of attentional deficits in patients with Parkinson's
      disease: evidence from a spatial orienting task.
AB  - Endogenous and exogenous shifts of attention were examined in nondemented
      patients with Parkinson's disease (PD). In the endogenous condition, an arrow was
      used to cue participants' attention to the possible location of an impending
      target, whereas in the exogenous condition, a brightened box was used to cue
      attention. Cues were either valid (i.e., the target appeared in the cued
      location) or invalid (i.e., the target appeared in a noncued location). The time
      between cue onset and target onset (stimulus onset asynchrony or SOA) was varied
      in each condition. The results indicated that PD patients were not differentially
      impaired in shifting attention at the shorter SOAs relative to normal controls.
      However, at longer SOAs, the PD patients demonstrated less of an effect from
      cueing than did the normal control participants. PD patients' differential effect
      from cueing was evident in both exogenous and endogenous conditions. These
      results suggest that PD patients may experience a rapid decay of attentional
      inhibition and do not support the notion that a decrement in processing resources
      underlies their attentional deficits. Moreover, these findings further support
      the notion that the basal ganglia may play an important role in attentional
      functions.

PMID- 9260444
TI  - Semantic priming impairment in HIV.
AB  - HIV+ subjects have shown impairment on tests of executive function including
      automatic attention and verbal tasks. Impairment of semantic priming in HIV
      patients would suggest a disruption of automatic semantic activation. We examined
      semantic priming in HIV+ individuals and HIV- control participants with no
      history of substance abuse, neurologic or psychiatric disorder unrelated to HIV.
      HIV+ participants were divided into cognitively normal and cognitively impaired
      subgroups on the basis of a neuropsychological battery of 15 tests. Participants
      were presented with English words and nonword letter strings and indicated if the
      stimulus was a word or nonword. The nonwords were orthographically and
      phonologically correct and were created by rearranging the letter sequence of
      words ("ulpit"). All words had an obvious antonym ("deep"); two-thirds were
      presented as sequential antonym pairs ("enter"-"exit"). There were no group
      differences in speed of response to nonwords, indicating no generalized reaction
      time deficit. While control and cognitively normal HIV+ participants showed an
      effect of priming on reaction time to correctly detected words, cognitively
      impaired HIV+ participants did not. The lack of semantic priming demonstrated by
      cognitively impaired HIV+ participants suggests that they have lessened
      activation of automatic semantic networks.

PMID- 9260445
TI  - Sense of time in children with ADHD: effects of duration, distraction, and
      stimulant medication.
AB  - A recent theory of ADHD predicts a deficiency in sense of time in the disorder.
      Two studies were conducted to test this prediction, and to evaluate the effects
      of interval duration, distraction, and stimulant medication on the reproductions
      of temporal durations in children with ADHD. Study I: 12 ADHD children and 26
      controls (ages 6-14 years) were tested using a time reproduction task in which
      subjects had to reproduce intervals of 12, 24, 36, 48, and 60 s. Four trials at
      each duration were presented with a distraction occurring on half of these
      trials. Control subjects were significantly more accurate than ADHD children at
      most durations and were unaffected by the distraction. ADHD children, in
      contrast, were significantly less accurate when distracted. Both groups became
      less accurate with increasing durations to be reproduced. Study II: Tested three
      doses of methylphenidate (MPH) and placebo on the time reproductions of the 12
      ADHD children. ADHD children became less accurate with increasing durations and
      distraction was found to reduce accuracy at 36 s or less. No effects of MPH were
      evident. The results of these preliminary studies seem to support the prediction
      that sense of time is impaired in children with ADHD. The capacity to accurately
      reproduce time intervals in ADHD children does not seem to improve with
      administration of stimulant medication.

PMID- 9260446
TI  - The influence of systemic lupus erythematosus on fetal development: cognitive,
      behavioral, and health trends.
AB  - In 1985, Gualtieri and Hicks proposed the immunoreactive theory to explain the
      higher prevalence of childhood neurodevelopmental disorders in males. The theory
      claimed that male fetuses are more antigenic to mothers, resulting in increased
      immunologic attack on the developing central nervous system, and increased
      probability of atypical brain development. Individuals with systemic lupus
      erythematosus (SLE) provide a unique situation in which to investigate this
      theory. We evaluated the parent-reported prevalence of five developmental
      problems (stuttering, other speech problems, hyperactivity, attention deficit,
      and reading problems) in two groups: 154 individuals ages 8-20 years born to
      women with SLE, drawn from six cities, and 154 controls of comparable age and sex
      whose mothers did not have SLE. Controls were drawn from a comparison group
      ascertained from randomly selected schools in one of the cities. Questions about
      handedness, immune disorders, and pregnancy and birth complications were also
      evaluated. Children of SLE mothers were shown to have more evidence of
      developmental difficulties, immune related disorders, and nonrighthandedness. For
      developmental problems, these findings were most marked in male children of SLE
      mothers. These results suggest that maternal immunoreactivity, as represented by
      women with SLE, may present a special risk factor for subsequent learning
      difficulties in their children, particularly males.

PMID- 9260447
TI  - The relationship of antiphospholipid antibodies to cognitive function in patients
      with systemic lupus erythematosus.
AB  - OBJECTIVE: To examine the relationship between antiphospholipid antibody
      positivity (expressed as the lupus anticoagulant) and cognitive dysfunction in
      patients with systemic lupus erythematosus (SLE). METHODS: Cross-sectional
      comparisons of lupus anticoagulant (LA) positive (N = 39) and negative (N = 79)
      patients and controls (N = 35) on a cognitive test battery; 22 LA-positive and 53
      LA-negative patients who had never experienced neuropsychiatric events (never-NP
      SLE) were also compared separately. RESULTS: LA-positive patients were 2 to 3
      times more likely than were LA-negative patients to be designated as cognitively
      impaired. As a group, LA-positive patients, particularly those in the never-NP
      SLE group, demonstrated lower performance primarily on tasks of verbal memory,
      cognitive flexibility, and psychomotor speed. CONCLUSIONS: LA positivity is
      associated with subclinical nervous system compromise, and a pattern of deficits
      compatible with subcortical involvement, possibly on the basis of ongoing LA
      related microthrombotic events or vasculopathy.

PMID- 9260448
TI  - A population-based analysis of qualitative features of the neuropsychological
      test performance of individuals with dementia of the Alzheimer type: implications
      for individuals with questionable dementia.
AB  - Qualitative features of the neuropsychological test performance of individuals
      with dementia of the Alzheimer type (DAT) were examined in a population-based
      study. Qualitative error scores were derived from measures of verbal and figural
      memory, verbal fluency and confrontation naming for 38 patients with clinically
      diagnosed DAT, 236 normal elderly (NE) individuals, and 72 others who were
      questionably demented and at risk (AR) for DAT. Persons with DAT made a greater
      proportion of intrusion and perseverative errors, and more lexical and semantic
      naming errors, than the NE participants. These measures provided fair specificity
      but poor sensitivity for the diagnosis of DAT, and a logistic model based on
      these measures correctly classified 98% of the NE participants, but only 29% of
      the DAT participants. The AR participants demonstrated a pattern of errors that
      was highly similar to that of the DAT patients, and when their scores were
      subjected to the logistic model, 90% were classified as NE and 10% as DAT. These
      results indicate that specific error types that have been associated with DAT in
      self-referred or clinic-based samples also occur in the general population to a
      greater degree in individuals with DAT or questionable dementia than in NE
      individuals. Furthermore, these qualitative features may have some diagnostic
      usefulness in that their presence provides reasonable specificity for DAT or
      questionable dementia.

PMID- 9260449
TI  - Improvement of hemispatial neglect with cold-water calorics: an
      electrophysiological test of the arousal hypothesis of neglect.
AB  - Introducing ice-water into the left ear of right-brain-damaged patients
      attenuates unilateral neglect symptoms. By examining EEG changes over each
      hemisphere during this procedure, we were able to test a hypothesis concerning
      the mechanism of cold-water calorics and the attention-arousal hypothesis of
      hemispatial neglect. We present a case study of an 83-year-old woman with a
      massive right-hemisphere CVA exhibiting severe hemispatial neglect. Caloric
      stimulation produced a leftward eye deviation to central position, and a
      temporary partial remission of neglect symptoms. Significant changes in EEG
      activation indicated a central mechanism associated with the regularization of
      eye gaze. Caloric stimulation also produced a significant interaction between EEG
      frequency band and hemisphere, indicating that while both hemispheres increased
      in cortical activation, the right hemisphere increase was significantly greater.
      This supports the activation-arousal hypothesis of neglect over the mutual
      inhibition model.

PMID- 9260450
TI  - ECG of the month. Brink of disaster. Second-degree AV block.

PMID- 9260451
TI  - Percutaneous tracheostomy.
AB  - Percutaneous tracheostomy is a new and somewhat controversial procedure which
      appears to be gaining in popularity. Methods described for this procedure include
      the single dilator technique, the percutaneous dilational technique, and the
      dilator forceps technique. The literature has been reviewed to date regarding the
      successes and failures of each of these methods and suggestions are made for
      future evaluations to determine the true utility of this procedure.

PMID- 9260452
TI  - Radiology case of the month. Calcified mass and indistinct retroperitoneal
      landmarks on abdominal radiograph. Ruptured abdominal aortic aneurysm.

PMID- 9260453
TI  - The journal 100 & 150 years ago. New Orleans Medical and Surgical Journal. August
      1847 and 1897.

PMID- 9260454
TI  - ATV-related central nervous system injuries in Louisiana.
AB  - All terrain vehicles (ATVs) have been associated with death and serious injury
      since their introduction into the marketplace. Fifteen cases of ATV-related brain
      and spinal cord injury reported to the Louisiana Central Nervous System Registry
      during 1995 were evaluated for severity, etiology, and outcome. Eleven (73%) of
      these injuries were sustained by persons under 18 years of age. Despite US
      Consumer Product Safety Commission and ATV manufacturer recommendations for age
      restrictions, ATVs continue to be popular recreational devices for children.

PMID- 9260455
TI  - Liability of peer review participants--a clue to the puzzle.

PMID- 9260456
TI  - Screening for asymptomatic cancers.
AB  - The overall age-adjusted cancer mortality rate in the United States declined by
      approximately 3.1% between 1990 and 1995. Prevention efforts and improved medical
      care were key factors in that success, and cancer screening will continue to be
      crucial in the campaign against the disease. The responsibility for screening
      patients for asymptomatic ovarian, cervical, skin, testicular, breast, prostate,
      and colorectal cancers lies chiefly with primary care physicians. Although no
      consensus has been reached, primary care physicians can review major screening
      guidelines from the American Cancer Society, American College of Physicians, US
      Preventive Services Task Force, and other groups to determine when such screening
      is appropriate.

PMID- 9260457
TI  - Management of the incidentally discovered adrenal mass or "incidentaloma".
AB  - The prevalence of an incidentally discovered adrenal mass or "incidentaloma" by
      abdominal computerized tomography (CT) scan is 1% to 2%. The majority of patients
      with incidentalomas do not have clinical manifestations nor require further
      treatments of their incidentalomas. Thus the goal for their management is two
      fold: 1) To identify and treat the hormonally hyperactive adrenal adenoma and the
      rare adrenal carcinoma, and 2) To avoid creating an iatrogenic disease of medical
      progress. An adrenal mass > or = 6 cm, excluding metastatic malignant disease,
      needs to be surgically resected due to the risk for carcinoma. The risk of
      primary adrenal cancer for a hormonally inactive lesion < or = 3 cm is extremely
      low and can be safely observed. Treatment for the hormonally inactive lesion
      between 3 and 6 cm must be individualized, based on age, specific scan
      characteristics (irregular border, local invasion, metastasis), and clinical
      status of the patient. All hormonally active adrenal adenomas should be
      surgically resected. In this article, we review the data to support the above
      recommendations.

PMID- 9260458
TI  - Coping with cancer.
AB  - In summary, the manner in which an individual and his or her family and friends
      adapt to the diagnosis of cancer is quite individual and complicated, and depends
      on a number of factors. It is important that patients realize that they should
      acknowledge their feelings to their physicians, family and friends so that these
      feelings can be validated. In this way they can be helped to find resources to
      enhance their coping abilities. There are many support groups that are now
      available for patients in various areas of cancer treatment. Efforts are underway
      to bring more of these issues to light in medical training so that physicians may
      be better prepared to strengthen a person's ability to cope with cancer and to
      live to the fullest extent possible.

PMID- 9260459
TI  - Drug use and physical trauma: risk factors for preterm delivery.
AB  - OBJECTIVE: The present investigation was undertaken to determine the incidence of
      alcohol, cocaine, and marijuana use among pregnant patients who suffered any type
      of physical trauma and to determine if the combination of substance use and
      physical trauma in pregnancy has extended perinatal implications. METHODS: In
      this single institution, prospective patient series undertaken over 18 months,
      all pregnant patients who suffered any type of physical trauma were considered
      for study. RESULTS: Among 6828 live births over an 18-month period, there were
      157 (2.3%) patients who reported physical trauma (insignificant = 153, minor = 2,
      severe = 2). Consent to screen for the presence of alcohol, marijuana, and
      cocaine was obtained from 85 (54%) patients with refusal by the remainder.
      Screening was positive in 11% for one or more substances. The perinatal morbidity
      and mortality for the 153 patients with insignificant trauma was 50:1000 and
      20:1000, respectively, all associated with preterm labor and delivery which
      occurred in 21% of the patients. None of the four patients with minor or severe
      trauma either had a positive drug/alcohol screen or any perinatal morbidity or
      mortality. No maternal mortality occurred. CONCLUSION: An 11% incidence of
      positive drug screens was encountered in consenting pregnant trauma victims and a
      21% incidence of preterm birth was encountered even in this patient population
      with so-called insignificant trauma.

PMID- 9260461
TI  - Expression of epidermal growth factor receptors and c-erbB-2 proteins in human
      astrocytic tumors.
AB  - Tumorigenesis is the result of sequential or multiple genetic alterations. The
      overexpression or amplification of various oncogenes in diverse human brain
      tumors have been observed. While numerous studies on the immunohistochemical
      demonstration of EGFR-overexpression have been reported, little has been found in
      the literature about the c-erbB-2 protein in human astrocytic tumors. In the
      present study, we evaluated the expression of EGFR and c-erbB-2 protein in 33
      astrocytic tumors with immunohistochemistry. According to the World Health
      Organization brain tumor classification, the study included 9 low-grade
      astrocytomas (grade 2), 15 anaplastic astrocytomas (grade 3), and 9 glioblastomas
      multiforme (grade 4). The positive EGFR immunoreactivity was detected in 28 (85%)
      of 33 tumors. The expression of EGFR increased with the grade of malignancy in
      low-grade astrocytomas (67%), anaplastic astrocytomas (87%), and glioblastomas
      (100%). For the expression of c-erbB-2 protein, 17 (51.5%) of 33 tumors were
      positive immunostain, including 3 low-grade astrocytomas (37.5%), 9 anaplastic
      astrocytomas (81.8%), and 5 glioblastomas (62.5%). Different degrees of
      immunoreactivity for c-erbB-2 protein were found in variant grades of
      astrocytomas. However, the positive immunostain of EGFR displayed moderate or
      strong reactivity. The coexpression of EGFR and c-erbB-2 protein was found in 17
      (15.5%) of 33 tumors. The results emphasize that the overexpression of EGFR
      parallels astrocytoma progession and higher frequency of c-erbB-2
      immunoreactivity was seen in snaplastic astrocytomas and glioblastomas than in
      low-grade astrocytomas.

PMID- 9260460
TI  - Synergestic effects of noise and aminoglycoside antibiotic (gentamicin) on
      auditory function in the gerbil.
AB  - Exposure to excessive noise can cause auditory impairment in people as well as in
      animals, which can be aggravated by many different ototoxic substances, such as
      aminoglycosides. In the present study, the gerbil was selected as the
      experimental animal because the gerbil has low-frequency auditory sensitivity
      that is similar to human beings. Auditory function in gerbils upon exposure to
      noise and/or gentamicin was evaluated from non-invasive records of brainstem
      auditory evoked potentials (BAEPs). Fifty mature male Mongolian gerbils were
      divided randomly into four groups. The control group was exposed neither to noise
      nor to gentamicin. The noise group was exposed to 100dBA noise ten hours a day
      for four weeks. The gentamicin group was treated with one dose of gentamicin, 75
      mg/Kg i.m., daily for four weeks. The noise + gentamicin group was exposed
      concurrently to both noise and gentamicin treatment. BAEPs were recorded from all
      gerbils 24 hours before any experimental treatment, then every week for eight
      consecutive weeks. Long-term exposure to noise and/or gentamicin treatment was
      found to reduce gerbil's body weight. The increase in auditory threshold upon
      concurrent exposure to both noise and gentamicin treatment (evaluated from BAEPs)
      exceeded the sum of effects caused by exposure to noise alone and to gentamicin
      alone. Although differences of peak or interpeak latencies among the four groups
      were not statistically significant, large standard deviations were noted in the
      noise+gentamicin group. Thus the apparent threshold shifts in gerbils indicated a
      major noise and/or gentamicin induced auditory impairment to the cochlea, and the
      slight latency variations probably suggested a minor injury to the auditory
      pathways. We emphasize that noise and aminoglycoside antibiotic gentamicin can
      cause damage to the hearing ability at the frequency range vital to human speech
      recognition, and their effects are synergetic.

PMID- 9260462
TI  - The prognosis of patients with cervical spondylotic myelopathy.
AB  - We studied 56 patients who received complete neurological examinations, image
      studies, or electrophysiological studies, and for these cervical spondylotic
      myelopathy was diagnosed at the Kaohsiung Medical College Hospital during the
      period 1988 to 1993. For the purposes of identifying possible prognosis factors
      and comparing the results of patients with conservative treatment versus
      operative treatment, we designed this study. Informed consent and a completed
      functional evaluation were obtained from 31 patients via physiatrist's visits. 17
      patients (male = 11, female = 6) mean age 52 years old received conservative
      treatment and 14 patients (male = 11, female = 3) mean age 50 years old received
      operative treatment. For the conservative group, the average follow-up was 54
      months and for the operative group, the average duration (from symptom and sign
      onset until operation) was 23 months. According to "The Japanese Orthopaedic
      Association Scale" and "The Recovery Rate Scale", we have evaluated the
      functional change of patients during the follow-up period and different possible
      prognosis factors have been analyzed. There is no significant difference in
      recovery rate whether patient's age is over 50 years old or whether the
      individual Pavlov ratio is smaller than 0.7. Interestingly, patients who received
      operation (anterior or posterior approach) within 18 months since symptom and
      sign onset were found to have a better recovery rate (p = 0.03). In our study,
      conservative management leads to 35% improvement and the operative management
      leads to 43% improvement. The results of proper cases selection and operation are
      superior to conservative treatment. If a patient has received a conservative
      treatment, routine re-evaluation is then very important for the early detection
      of progressive compression myelopathy signs.

PMID- 9260463
TI  - Changes in lysyl oxidase activity and calcium content during the healing of tooth
      extraction wounds.
AB  - The typical wound healing process after tooth extraction includes several
      important biological reactions. The collagen fiber, which is the main organic
      component of connective tissue, plays an important role in the formation of
      granulation tissue and also bone tissue. Maturation of collagen is controlled by
      the intermolecular crosslinks in the collagen fibers. Lysyl oxidase, which
      catalyzes the corresponding aldehyde formation from certain lysyl and
      hydroxylysyl residues in collagen and elastin in the first step of the linking
      reaction, is the only known enzyme required in the crosslinking process. This
      study was designed to analyze changes in the lysyl oxidase activity and calcium
      content during the healing of rabbit tooth extraction wounds and to survey the
      relationship between them. Healing tissue in the extraction sockets was removed
      1, 2, 3, 4, 5, 7, 10, 14, 21, 28, and 56 days postoperatively. After
      decalcification, lysyl oxidase was extracted from wound tissue, and activity of
      this enzyme was examined by tritium-release assay. Radiographs and histologic
      sections were also obtained in each group. The results show that lysyl oxidase
      activity can be detected on the first day postoperatively and that it increases
      sharply from days five to seven, reaching the peak value on the seventh day.
      After that, enzyme activity decreases gradually and returns to normal range on
      day 14. Histologically, the healing sockets were filled mainly with young fibrous
      connective tissue at day seven; osteoid tissue could be found on the lateral wall
      and fundus of the extraction sockets at the same time. Accompanying the formation
      of new bone, calcium content increased conspicuously from day 7 to day 14. These
      results indicate that lysyl oxidase predominantly acts to promote cross-linking
      of the abundantly synthesized collagen in the early stage of healing of rabbit
      tooth extraction wounds. When minerals were precipitated at a great rate in the
      newly-formed bone, lysyl oxidase activity was concurrently decreased.

PMID- 9260464
TI  - Clinical study of dens evaginatus cases with pulpal involvement.
AB  - The objective of the present study was to investigate the incidence, clinical
      findings, diagnosis and treatment of evaginated teeth with pulpal involvement.
      Five hundred and three cases requiring endodontically treated premolars were
      studied at Kaohsiung Medical College Hospital. We observed 23 (4.6%) evaginated
      teeth with pulpal involvement out of the 503 samples studied here. Of the 23
      teeth, mandibular second premolars comprise the largest portion. Clinically, all
      tubercles of pulpally involved evaginated teeth had been worn down by attrition
      and all these teeth showed negative response in vitality tests. The study
      indicated that 17 cases had sinus tracts, 1 tooth had discoloration in crown
      portion, 1 case had facial asymmetry and 6 teeth had a painful history.
      Radiographs confirmed that 21 cases had apical or lateral rarefaction, 1 tooth
      had thickened periodontal ligament and 8 teeth had incomplete root formation.
      Clinical diagnosis included pulp necrosis (23 cases), acute apical periodontitis
      (3 cases), chronic apical periodontitis (4 cases), suppurative apical
      periodontitis (17 cases)and Garrer' osteomyelitis (1 case). After the treatment,
      13 teeth showed satisfactory results. The treatment on 2 teeth was failed, 1
      tooth had root fracture and 7 teeth had loss of follow-up. We conclude that the
      evaginated teeth can hence be preserved even if they are pulplly infected and
      have an incomplete root apex.

PMID- 9260465
TI  - Sequence of a human E2F-4 pseudogene with shortened AGC trinucleotide repeats.
AB  - We have isolated a human genomic DNA fragment of 0.7 kb by polymerase chain
      reaction (PCR) using human E2F-4 gene primers. Sequence analysis indicates that
      this DNA comes from a processed E2F-4 pseudogene. Its sequence is 75% identical
      to the human E2F-4 cDNA, and bears several deletions and insertions. A 30 bp
      deletion shortens the 13 AGC repeats in the E2F-4 gene by 10 repeats. The
      sequence data also suggest that another 65 bp deletion and some small insertions
      may be generated by replication errors on template pairing.

PMID- 9260466
TI  - A case of double inferior venae cavae.
AB  - In this study, we present a case of double inferior venae cavae found among 252
      Taiwanese cadavers that were dissected in the gross anatomy laboratory of
      Kaohsiung Medical College from 1978 to 1996. The lumbar portion of the normal
      inferior vena cava is embryologically formed by the persistence of the right
      supracardinal vein. Persistence of the left one gives rise to the left inferior
      vena cava and the persistence of the bilateral ones, the double inferior venae
      cavae. In this case, there is an anastomosis between the right and left inferior
      venae cavae. The anastomotic type of this anomaly seems to be more common than
      the non-anastomotic one.

PMID- 9260467
TI  - Spinal epidural abscess--a case report.
AB  - Despite modern medical advances, the morbidity and mortality rates associated
      with spinal epidural abscess remain significant, and the diagnosis is elusive.
      The incidence of spinal epidural abscess is approximately one to two cases per
      10,000 among all patients admitted to hospitals. The symptoms of spinal epidural
      abscess are varied but include lower back pain, fever, local tenderness and
      neurological deficit especially in such high risk groups as patients with
      diabetes, intravenous drug abuse, chronic renal failure, alcoholism, liver
      disease and immunocompromization. Accumulation of data is difficult in that many
      physicians will never see a case during their careers. Herein, we present a case
      with lower back pain associated with both lower legs weakness. His abdomenon CT
      revealed retroperitonium and right perirenal abscess. External drainage as well
      as antibiotic treatment was done immediately. However, the lower legs weakness
      became severe and a lumbar spine MRI revealed T11-L4 epidural abscesses and L2-3
      intervertebral space pus formation. Then, the patient was transfered to our
      Neurosurgical Ward for further treatment. His postoperative condition improved in
      both lower legs. This case report is to enhance the recognition and treatment of
      spinal epidural abscess, a rare affliction.

PMID- 9260468
TI  - Intrasellar and suprasellar germinoma.
AB  - A 15-year-old male was admitted to our hospital with diabetes insipidus, headache
      and bitemporal hemianopia and a computed tomogram (CT) revealed an intra- and
      suprasellar tumor. Differential diagnosis between large intra- and suprasellar
      germinoma and pituitary adenomas is quite difficult based on CT. After comparing
      our case with past literature of reported cases of intrasellar and suprasellar
      germinoma, we found that an enhanced mass posterior to the pituitary gland on the
      midsagittal magnetic resonance imaging (MRI) and absence of the high signal
      intensity of the posterior lobe on T1-weighted MRI in patients with diabetes
      insipidus indicated germinoma rather than a pituitary adenoma. Transphenoid
      approach and appropriate radiotherapeutic management were administered with a
      good result.

PMID- 9260469
TI  - The erosion of medical privacy today.

PMID- 9260470
TI  - Small cell carcinoma of the prostate: a case report and review of the literature.
AB  - Primary small cell carcinoma of the prostate is rare. A case of primary small
      cell prostate cancer treated with radiation and chemotherapy is presented, and 33
      previously published case reports are reviewed. Most of the patients (61%) had
      mixed tumors (small cell and adenocarcinoma) at diagnosis or had a history of
      adenocarcinoma of the prostate. Prostate specific antigen (PSA) data was
      available in 11 patients and was abnormal in 4 (36%). Once small cell carcinoma
      was diagnosed, 70% of patients had metastatic disease. Visceral metastases were
      common. Only one of seven patients responded to hormonal therapy, and two of
      eight patients responded to chemotherapy. Overall prognosis was poor.

PMID- 9260471
TI  - Neuroleptic malignant syndrome and acute myocardial infarction: case report and
      review.
AB  - The neuroleptic malignant syndrome (NMS) is a potentially life threatening
      reaction usually observed following administration of dopaminergic antagonists
      (neuroleptic medications, e.g., phenothiazines, thioxanthenes, and haloperidol).
      NMS is characterized by mental status changes, muscle rigidity (and movement
      disorders such as dyskinesias and akathisias), leukocytosis, hyperthermia, and
      autonomic dysfunction. Because of the variants of this disease, the physician
      must remain alert to its possibility when confronted with emergency care of
      patients having received neuroleptics, particularly when hypermetabolic states
      are etiologically consequential in the development of other disease processes,
      for example, acute myocardial infarction.

PMID- 9260472
TI  - Progress in the treatment of childhood cancer.

PMID- 9260473
TI  - When people with developmental disabilities present to community practitioners.
AB  - This article describes the problems involved in the global medical assessment of
      persons with developmental disabilities who present with behavioral changes.
      Solutions offered include anticipating the difficulties in treating this group
      and taking steps to insure adequate information is provided. Community providers
      are cautioned against assuming behavioral changes in this population are
      psychiatric in nature. Case examples illustrate the quality of life improvements
      that can result from relatively minor medical interventions in persons initially
      thought to have psychiatric difficulties.

PMID- 9260474
TI  - A 69-year-old woman with hemoptysis, bilateral alveolar infiltrates, and
      microscopic hematuria.

PMID- 9260475
TI  - A long forgotten tribute to the "emperor" recalled on his 200th birthday
      anniversary.

PMID- 9260476
TI  - Chronic systemic aspergillosis.

PMID- 9260477
TI  - Fungal infections of the cardiovascular system--a review.
AB  - Various yeasts and filamentous fungal infections of human and animal heart and
      blood vessels, as well as the experimental investigations, are reviewed.
      Clinical, diagnostic, therapeutic and pathological aspects are discussed. The
      prevalence of mycotic infection of the heart, once considered to be an uncommon
      disease, has been reported frequently during recent years. The rate will
      certainly be higher if cases are more thoroughly investigated.

PMID- 9260478
TI  - Plasma and tissue concentrations of fluconazole and their correlation to
      breakpoints.
AB  - The prediction of clinical outcome during antifungal therapy is an issue of
      paramount importance in clinical research, because no consistently reliable
      parameters are available. Minimum inhibitory concentration (MIC) values and
      breakpoint interpretation may serve as surrogate criteria until standardized in
      vitro antifungal susceptibility testing is developed, especially for fluconazole.
      With reproducible susceptibility testing methods for Candida species now
      available, tentative fluconazole interpretive breakpoints derived from MIC values
      determined by the National Committee on Clinical Laboratory Standards (NCCLS) M27
      T broth macrodilution method are open for public comment. Besides the in vitro
      susceptibility of the fungus, clinical response to antifungal therapy with
      fluconazole depends to a great extent on the daily dose and corresponding plasma
      and tissue concentrations. Promising results from a few dose-finding studies in
      non-neutropenic patients show that fluconazole doses of up to 1000 mg day-1
      result in higher clinical response rates than lower dosages. Therapeutic success
      depends substantially on achieving fluconazole plasma and tissue levels that are
      sufficiently higher than MIC values indicated by in vitro testing. However, this
      simplified concept must be related to the clinical situation and it is essential
      to consider the immunological status and underlying disease of the patient.
      Misinterpretation of MIC values may result in selection of an antifungal agent
      for life-threatening infections that does not provide optimal efficacy or
      toleration.

PMID- 9260479
TI  - Adhesion of Candida albicans to epithelial cells--effect of nikkomycin.
AB  - This study investigated the effect of the chitin synthetase inhibitors, the
      nikkomycins (NZ and NZ+NX), on Candida albicans adhesion to buccal epithelial
      cells (BECs) in vitro. The effect was expressed in reduced chitin synthetase
      activity and chitin content of fungal cells. In vitro adhesion assays to BECs of
      Candida exposed to NZ and NZ+NX revealed reduced adhesion values. Light, scanning
      and transmission electron microscopy (SEM, TEM) of NZ-treated and untreated micro
      organisms showed changed fungal morphology and reduced adherence of the treated
      yeasts. Scanning electron microscopy of NZ-treated C. albicans labelled with gold
      conjugated wheatgerm agglutinin (WGA) revealed less labelling than in the
      untreated organisms. A close contact between the fungus and the epithelial cell
      at a site with intense WGA-gold labelling was noted in TEM experiments. The data
      point to the involvement of chitin in the adhesion of C. albicans to epithelial
      cells.

PMID- 9260480
TI  - Activated CD8+ T cells are involved in elimination of Candida albicans from the
      livers of mice.
AB  - We have investigated the course of infection of Balb/c mice with Candida
      albicans. After intravenous infection of mice, the yeasts were evenly distributed
      in the liver sections. There was a 90% reduction in the yeasts found within 7
      days after infection. This reduction was accompanied by an increase in the number
      of phagocytic cells (Mac-1+, Gr-1+) in cellular infiltrates around the yeast
      cells. Furthermore, both CD4+ and CD8+ T lymphocytes were found in these
      pseudogranulomata, with the CD8+ cells in the periphery. Peak amounts of the cell
      types investigated were found at days 5 and 6 post infection, with an increased
      expression of receptors for interleukin 2 (IL-2R) on the surface of CD8+ cells.
      At day 14 of infection, the same levels as those in control mice were reached. At
      this time, the yeasts were virtually eliminated from the liver. By using
      simultaneous detection of cell surface markers and yeast cells in
      immunohistology, these data demonstrate the close association of fungal cells,
      phagocytes, TH and TC cells in pseudogranulomata during elimination of Candida
      albicans from the livers of mice.

PMID- 9260481
TI  - Retrospective analysis of yeast colonization and infections in paediatric bone
      marrow transplant recipients.
AB  - Sixty-four paediatric patients who underwent allogeneic (n = 35), autologous (n =
      28) or syngeneic (n = 1) bone marrow transplantation (BMT) between 1992 and 1994
      were evaluated retrospectively. As antifungal prophylaxis, all patients received
      amphotericin B tablets and 62 of 64 (96.9%) received oral fluconazole. Weekly
      surveillance cultures revealed fungal colonization in 35 patients (54.7%). Six
      patients (9.4%) were colonized before BMT only, 17 (26.6%) after BMT only and 12
      (18.8%) both before and after BMT. Candida albicans was the most frequently
      isolated fungus [21 of 46 fungal isolates (45.7%)], followed by C. glabrata [14
      isolates (30.4%)]. Non-albicans species of Candida were most frequently isolated
      after BMT from the faeces, often in high numbers. Autologous marrow recipients
      had a higher fungal colonization rate both before and after BMT than allogeneic
      marrow recipients. One patient suffered from invasive pulmonary aspergillosis
      after BMT. No fungaemias or deep-seated yeast infections were observed. Six of
      the seven patients who had to be treated with intravenous amphotericin B because
      of antibiotic-refractory fever had undergone autologous BMT. Multivariate
      analysis of various parameters showed only pre-BMT yeast colonization to be
      independently associated with post-BMT colonization. Thus, systemic mycoses
      occurred only rarely in this study population; however yeast colonization after
      BMT (especially with non-albicans species) was a frequent event in spite of
      double prophylaxis with oral amphotericin B and fluconazole.

PMID- 9260482
TI  - Dermatophytomycoses in children in rural Kenya: the impact of primary health
      care.
AB  - In a survey of 5780 children from 13 schools in rural Kisumu District (western
      Kenya) in 1993, a prevalence rate of dermatophytomycoses of 10.1% was found.
      Three-quarters of the affected children suffered from tinea capitis (prevalence
      rate 7.8%), caused by Microsporum audouinii var. langeronii, Trichophyton
      violaceum and Microsporum canis. In 1994, a dermatology programme within the
      primary health care system was started. Twelve community health workers (CHWs),
      trained in diagnosis and treatment of the most common skin diseases, carried out
      regular school visits once a week. All dermatophytomycoses, dry forms of tinea
      capitis included, were treated locally with Whitfield's ointment. In 1995 the
      prevalence rate of fungal skin infections in the same schools was found to be
      9.3%; the difference to 1993 was not significant. Only tinea capitis, with a
      prevalence rate of 5.8%, showed a significant reduction (P < 0.05). Altogether, a
      distinctive improvement regarding the extent and the severity of
      dermatophytomycoses could be noticed. In the cultures from tinea capitis,
      Microsporum canis was not found to be present. Trained community health workers
      are capable of the diagnosis and treatment of fungal skin infections of children
      in rural areas, which leads to a reduction in the prevalence of tinea capitis.

PMID- 9260483
TI  - The cholesterol century.

PMID- 9260484
TI  - Serum cholesterol and coronary heart disease--a public health perspective.

PMID- 9260485
TI  - Effects of ketoconazole on plasma lipids and lipoprotein(a) in familial
      hypercholesterolaemia, compared with simvastatin.
AB  - BACKGROUND: Ketoconazole is an imidazole derivative that is active as a broad
      spectrum antifungal agent. It is also an inhibitor of cholesterol production both
      in vivo and in vitro. METHODS: We compared the effect of low-dose ketoconazole
      (200 mg/day) or simvastatin (20-40 mg/day) on lipids, lipoproteins and
      lipoprotein(a) [Lp(a)] in 10 patients with familial hypercholesterolaemia.
      RESULTS: Ketoconazole reduced serum total cholesterol and low-density lipoprotein
      (LDL)-cholesterol by 7.6 and 9.7%, respectively. Simvastatin was more effective,
      the respective changes being -34.4 and -40.6%. Serum triglycerides and high
      density lipoprotein (HDL) were unchanged by ketoconazole therapy, whereas
      simvastatin decreased triglyceride levels by 33.8% and increased HDL-cholesterol
      levels by 8.7%. Median Lp(a) levels tended to increase during simvastatin and to
      decrease during ketoconazole therapy. However, due to the wide range of baseline
      concentrations of Lp(a), these changes were not significant. CONCLUSIONS:
      Ketoconazole has some hypocholesterolaemic potential, but the effect of
      simvastatin is much more pronounced. The increase in Lp(a) during simvastatin
      therapy has been reported earlier, whereas ketoconazole does not exhibit an
      effect on the level of Lp(a).

PMID- 9260486
TI  - LDL-cholesterol lowering and atherosclerosis--clinical benefit and possible
      mechanisms: an update.
AB  - The results of several lipid-lowering randomized trials have been released during
      the past years and have confirmed the lipid hypothesis. Reduction of cholesterol
      by potent drugs in clinically symptomatic or asymptomatic patients with above
      average cholesterol levels will substantially reduce the risk of coronary events.
      The present article gives a review of potent low-density lipoprotein cholesterol
      lowering treatments and discusses developments in hypolipidaemic therapy in
      relation to recent primary and secondary prevention studies. In addition,
      possible mechanisms of cholesterol lowering in retardation of the atherosclerotic
      process are summarised.

PMID- 9260487
TI  - Tailor-made chemotherapy for cancer patients.
AB  - Dosages of anticancer agents are usually calculated from a uniform standard-the
      body surface area (BSA). Although the BSA is proportionate to many physiological
      functions, it is however only partially related to the overall drug clearance.
      Consequently, a wide variability in drug exposure and drug concentrations can be
      found between patients, by which some experience little toxicity, while others
      may show severe toxic symptoms. It seems clear that monitoring of plasma drug
      concentrations can be a useful tool to further optimize current cancer
      chemotherapy. The problem that pharmacokinetic parameters are usually generated
      from concentration-time profiles obtained after multiple venepunctures can be
      reduced by applying limited sampling models (LSM). Other tailor-made dosing
      strategies include the Calvert formula for carboplatin dosing and strategies
      based on the characteristics of the individual patient. It can be concluded that
      the determination of pharmacokinetic parameters and adjustment of the drug dose
      in each patient to a predefined 'target' value with an optimal therapeutic
      outcome, could contribute substantially to improvement of current
      chemotherapeutic treatment.

PMID- 9260488
TI  - Acute folate deficiency in a critically ill patient.
AB  - A 19-year-old male patient developed thrombocytopenia and leukopenia due to acute
      folate deficiency while recovering from a multiple organ failure syndrome. Risk
      factors for acute folate deficiency are extensive tissue damage due to sepsis,
      trauma or surgery and acute renal failure requiring renal replacement therapy.
      The diagnosis is based on bone marrow examination showing marked megaloblastic
      changes whereas serum folate levels and red cell folate levels are normal.
      Recognition of this serious complication of critical illness is important because
      it should be readily prevented by folic acid therapy.

PMID- 9260489
TI  - A rare case of disseminated actinomycosis caused by Actinomyces meyeri.
AB  - A case of disseminated actinomycosis caused by Actinomyces meyeri in a 43-year
      old man is described. The patient presented with signs of pericarditis, weight
      loss, dry cough, and subsequently an inferior vena cava syndrome. Diagnosis of
      thoracic as well as abdominal actinomycosis was made 4 months after admission.
      This article stresses the importance of considering the diagnosis of the disease.
      Cure was achieved by administering penicillin for several months.

PMID- 9260490
TI  - Severe upper abdominal pain due to a large hepatocellular adenoma.
AB  - A large hepatocellular adenoma was diagnosed in a female patient who was referred
      for severe upper abdominal pain. She had been using oral contraceptives over a
      period of 14 years. The clinical features, diagnosis and treatment are discussed.

PMID- 9260491
TI  - Views on how the electrical activity that the brain generates reflects the
      functions of different language structures.
AB  - Human language is what it is because of its function and its implementation. We
      are far from understanding how language comprehension is carried out by the human
      brain. This task can be made easier by considering that evidence for the what and
      how of language comes from the study of linguistics, psychology, and
      neuroscience. The approach outlined herein describes how these different sources
      of evidence can be combined in studies of written and spoken sentence processing
      by using a measure of the brain's electrical activity. The outcome is a more
      temporally precise view of the analysis of language structures in our minds and
      brains.

PMID- 9260493
TI  - The effect of unconditional stimulus modality and intensity on blink startle and
      electrodermal responses.
AB  - Attentional accounts of blink facilitation during Pavlovian conditioning predict
      enhanced reflexes if reflex and unconditional stimuli (US) are from the same
      modality. Emotional accounts emphasize the importance of US intensity. In
      Experiment 1, we crossed US modality (tone vs. shock) and intensity in a 2 x 2
      between-subjects design. US intensity but not US modality affected blink
      facilitation. In Experiment 2, we demonstrated that the results from Experiment 1
      were not due to the motor task requirements employed. In Experiment 3, we used a
      within-subjects design to investigate the effects of US modality and intensity.
      Contrary to predictions derived from an attentional account, blink facilitation
      was larger during conditional stimuli that preceded shock than during those that
      preceded tones. The present results are not consistent with an attentional
      account of blink facilitation during Pavlovian conditioning in humans.

PMID- 9260492
TI  - Daily mood states and ambulatory blood pressure.
AB  - In this study, we examined relationships between moods and both ambulatory blood
      pressure and heart rate in 197 men and women college students. Participants who
      reported frequently feeling angry during the day had higher levels of blood
      pressure, especially diastolic pressure during sleep. Reports of sad feelings
      were positively correlated and reports of pleasant or happy were negatively
      correlated with diastolic pressure during sleep. Participants scoring high on
      hostility and anxiety trait measures and low on defensiveness reported negative
      moods more frequently. Cluster analysis identified different mood profiles.
      Participants characterized by reports of all negative moods plus anger had high
      scores on trait hostility and consistently higher levels of blood pressure,
      particularly diastolic pressure during sleep. Heart rate was not related to mood
      reports. Hostile and anxious behavioral dispositions may play a role in sleep
      disturbance and high levels of blood pressure. Positive moods may counter these
      effects.

PMID- 9260494
TI  - Event-related potential (ERP) asymmetries to emotional stimuli in a visual half
      field paradigm.
AB  - To investigate the hypothesis of a right hemispheric superiority in negative
      emotional processing, event-related potentials (ERPs) were recorded from 17 sites
      (Fz, Cz, Pz, F3/4, F7/8, C3/4, T7/8, P3/4, P7/8, O1/2) in a visual half-field
      paradigm. While maintaining fixation, right-handed women viewed pictures of
      patients with dermatological diseases before (negative) and after (neutral)
      cosmetic surgery. A principal components analysis with Varimax rotation performed
      on ERPs revealed factors identified as N1, N2, early P3, late P3, and slow wave.
      Repeated measures analyses of variance performed on factor scores revealed a
      significant effect of emotional content for all factors except for N1. However,
      asymmetries in emotional processing were restricted to N2 and early P3, with
      maximal effects over the right parietal region. N2-P3 amplitude was augmented for
      negative and reduced for neutral stimuli over right hemisphere regions. Visual
      field presentation interacted with these asymmetries in enhancing amplitudes
      contralaterally for early but ipsilaterally for late ERP components. Overall,
      findings for N2 and P3 support theories of an asymmetry in emotional processing.

PMID- 9260496
TI  - Event-related potential correlates of interference between cognitive performance
      and tonic experimental pain.
AB  - In this study, we examined cognitive function during experimental pain induced by
      an ischemic upper-arm tourniquet. During pain and control conditions, individuals
      performed a memory search task and an oddball task. Reaction time, errors, and
      event-related potentials in response to task stimuli were evaluated. Pain reduced
      accuracy and changed the response-type dependency of errors and the reaction time
      within the memory search task: false rejections but not false acceptances
      increased, and rejections were faster than acceptances during pain, whereas the
      opposite occurred during control conditions. The memory probes elicited an N275
      that increased and a P300 that decreased in amplitude during pain. Pain also
      reduced amplitudes of P200 and P300 from the oddball task. N275 enhancement was
      greater in nonaffected than affected individuals, suggesting its association with
      focused attention that inhibited disruption by pain. P300 attenuation is
      interpreted as an indication that cognitive involvement in pain diminishes the
      attention resources allocated to a concurrent cognitive task.

PMID- 9260495
TI  - Maternal exposure to influenza and cold in pregnancy and electrodermal activity
      in offspring: the Mauritius Study.
AB  - Data are in conflict concerning whether a mother's exposure to influenza in
      pregnancy gives rise to an increased probability that her offspring will develop
      schizophrenia. In Northern Hemisphere studies, exposure to influenza and cold
      tend to be confounded. The present study, carried out in Mauritius, examines the
      effect of maternal exposure to the virus and separately to cold on aspects of
      electrodermal activity that have been shown in other studies to be related to
      schizophrenia. The findings are that maternal exposure to influenza in the second
      and third trimesters gives rise to children who at the age of 3 years show
      electrodermal hyperresponsivity, whereas exposure to cold in the same periods
      gives rise to children who tend to be hyporesponsive. In both instances, exposure
      tends to produce lower levels of tonic activity than in those not exposed to the
      virus or to cold.

PMID- 9260497
TI  - Prepulse inhibition decreases as startle reactivity habituates.
AB  - In the present study, I investigated the effect of stimulus repetition on human
      startle eyeblink reflex inhibition (PPI) by a prepulse. Participants were
      assigned to one of three groups (n = 14 each), in which they received 18 trials
      of (a) noise startle stimuli presented alone or preceded by 1000-Hz tone
      prepulses, (b) startle stimuli presented alone, or (c) prepulses presented alone.
      All participants then received 18 more trials of startle stimuli presented alone
      or preceded by 1000-Hz tone prepulses, followed by 6 trials of startle stimuli
      presented alone or preceded by 2000-Hz tone prepulses. As trials progressed,
      startle eyeblink electromyogram magnitude habituated and PPI decreased. PPI was
      not affected by the repeated presentation of the prepulses alone but decreased
      with the repeated presentation of the startle stimulus alone. Changes in the
      frequency of the prepulse had no significant effect on PPI. These data suggest
      that the reduction of PPI that is seen across trials is not due to habituation of
      the prepulse but is related to startle reactivity in control trials, which is
      reduced by habituation.

PMID- 9260498
TI  - Fear-potentiated startle conditioning in humans: explicit and contextual cue
      conditioning following paired versus unpaired training.
AB  - Conditioned fear in response to explicit and contextual cues was examined using
      the startle reflex in three groups of participants over two sessions separated by
      4-5 days. The conditioned stimulus (CS) was paired with an aversive unconditioned
      stimulus (US) (shock) during conditioning in the paired but not in the unpaired
      group. In the reaction time (RT) group, the US was a nonaversive visual signal
      for an RT task. In the paired group, the CS potentiated startle in the
      postconditioning phase. This conditioned response was fully retained over the
      retention interval. There was no substantial change in baseline startle (startle
      delivered in the absence of CS). By contrast, startle was not potentiated by the
      CS in the unpaired group, but baseline startle was increased from Session 1 to
      Session 2. In the RT group, startle was not affected by the CS, and baseline
      startle was reduced from Session 1 to Session 2. These results suggest that
      paired presentations of a CS and an aversive US result in conditioned fear in
      response to the CS but little contextual fear, whereas unpaired presentations of
      a CS and US leads to poor explicit cue conditioning but substantial contextual
      fear.

PMID- 9260499
TI  - Cardiovascular responses during effortful active coping and acute experience of
      anger in women.
AB  - This study addresses the question of whether effortful active coping and anger
      provocation add in their effects on cardiovascular responses. Heart rate (HR),
      systolic blood pressure (SBP), and diastolic blood pressure (DBP) responses of 64
      female students were collected during an active versus nonactive coping task with
      and without provocation. After a baseline period, women did mental arithmetic
      (active coping) or read numbers aloud (nonactive coping). Half of each group was
      then additionally provoked. Ratings of the emotional states (Positive and
      Negative Affect Scale) indicate that provocation led to an increase in anger, but
      not in fear or negative or positive affect. Effortful active coping and
      provocation elevated cardiovascular activity. Although active coping enhanced all
      cardiovascular variables, provocation particularly affected HR and DBP. The
      effects of active coping and provocation on HR and DBP but not on SBP were
      additive and probably were produced by different physiological mechanisms.

PMID- 9260500
TI  - Sensitivity to mechanical stimuli and the role of general sensory and perceptual
      processes in heartbeat detection.
AB  - Sensitivity to heartbeat sensations is commonly assessed using tasks that require
      individuals to judge the simultaneity of heartbeats and tones. In two
      experiments, we investigated the suitability of this paradigm for examining
      cardioception. In the first experiment, participants judged the simultaneity of
      near-threshold vibrations and suprathreshold tones. Precision in judging
      vibration-tone simultaneity was directly related to the detectability of the
      mechanical stimuli, thereby supporting use of the simultaneity paradigm to assess
      heartbeat detection. In the second experiment, we examined the influences of
      sensitivity to mechanical stimuli and the ability to make intermodality
      simultaneity judgments on the precision of heartbeat detection. We measured
      participants' vibrotactile thresholds, precision in judging light-tone
      simultaneity, and precision in judging heartbeat-tone simultaneity. The ability
      to judge the simultaneity of lights and tones accounted for 24.3% of the variance
      in precision of heartbeat detection, and mechanical sensitivity accounted for a
      further 8.5%.

PMID- 9260501
TI  - Cerebral processing of words and the development of chronic pain.
AB  - The processing of pain-related, body-related, and neutral words was assessed in
      individuals with prechronic pain and matched healthy controls. Integrated surface
      electromyogram, heart rate, skin conductance level, and visual event-related
      potentials from 11 electrode sites were recorded during the presentation of three
      word types at perception threshold. Startle responses were recorded from words
      presented above perception threshold. The patient and control groups did not
      differ in recognition performance. Pain-related words evoked an enhanced early
      component (N100) of the visual event-related potential only in the prechronic
      pain group. In both groups the late slow wave and the startle response were
      enhanced for body- and pain-related words compared with those for neutral words.
      All word types elicited larger late positivities in the prechronic pain group and
      in the right compared with the left hemisphere. These data suggest differential
      cortical processing of pain-related material in persons at a prechronic pain
      stage.

PMID- 9260502
TI  - Attentional modulation of the cardiac defense response in humans.
AB  - How cardiac components of the defense reaction are modulated by attentional
      factors related to sensory intake versus sensory rejection was examined. Forty
      eight men participated in a test of the heart rate response to three
      presentations of an intense auditory stimulus while performing one of three
      attentional tasks during the 80 s following stimulus onset: (a) internal
      (rejection) task, (b) external (intake) task, and (c) no task. Results showed a
      potentiation of the defense response only under the external attention condition.
      We concluded that defensive reactions, far from provoking the rejection of the
      aversive stimulus, require allocation of attention to processing that stimulus in
      detail.

PMID- 9260504
TI  - Sleep disorders easy to miss ... or misdiagnose.

PMID- 9260503
TI  - The concurrent recording of electroencephalography and impedance cardiography:
      effects on EEG.
AB  - Three experiments were performed testing the effects of a variety of impedance
      cardiograph electrode types and recording arrangements on recorded
      electroencephalography (EEG) using either a monopolar single-ear reference or a
      physically linked ears reference. EEG was recorded either alone or concurrently
      with an impedance cardiograph. When the cardiograph was recorded using a spot
      electrode for the top current-inducing electrode, there was an overall decrease
      in power density of the EEG, and this effect was dependent on the location of the
      recording electrode. This effect was diminished when the top cardiograph spot
      electrode was replaced by a mylar-coated neck band electrode and EEG was recorded
      using a monopolar, single-ear reference. However, there tended to be an overall
      increase in log power density of the EEG in each frequency band below 60 Hz when
      less technologically advanced EEG amplifiers were used. This effect was
      diminished if the EEG was recorded using a physically linked ears reference.
      Recommendations for the concurrent recording of EEG and impedance cardiography
      are discussed.

PMID- 9260506
TI  - Water hardness and cardiovascular death rates in Tennessee.

PMID- 9260505
TI  - Failure to monitor.

PMID- 9260507
TI  - Pediatrics and the Nashville General Hospital--Part II.

PMID- 9260508
TI  - Hypertensive intracranial hemorrhage.

PMID- 9260509
TI  - Hypothermia: impact on the trauma victim.
AB  - Secondary hypothermia may present the clinician with an extraordinary set of
      challenging problems. Rapid rewarming using both passive and active techniques is
      essential to correct the many reversible changes associated with hypothermia.
      Despite aggressive management, secondary hypothermia continues to exact a large
      toll in terms of the mortality of trauma victims.

PMID- 9260510
TI  - The development of the prehospital EMS system in Tennessee.

PMID- 9260511
TI  - Hematochezia and syncope in a 21-year-old man.

PMID- 9260512
TI  - Airbags and trauma.

PMID- 9260513
TI  - Exploring and explaining epigenetic effects.

PMID- 9260514
TI  - Epigenetic phenomena in filamentous fungi: useful paradigms or repeat-induced
      confusion?
AB  - Epigenetic mechanisms can serve as genome defense systems. In haploid nuclei of
      special sexual cells of fungi, such as Neurospora and Ascobolus, duplicated genes
      are silenced by hypermutation, DNA methylation, or both. In some cases, DNA
      introduced into the genome of Neurospora cells by transformation can also inhibit
      homologous genes by a silencing mechanism that does not involve DNA pairing or
      methylation and appears to be post-transcriptional. Transforming DNA can also
      trigger de novo methylation in vegetative cells, which then causes
      transcriptional silencing. The rules governing silencing in vegetative cells of
      fungi are undefined, but repeated sequences seem particularly susceptible to
      these processes. Thus, fungi exhibit both repeat-induced and repeat-associated
      silencing mechanisms. Additionally, some native genes depend on homologous
      pairing in the diplophase for proper regulation. Together, these processes should
      limit the proliferation of transposable elements and serve to preserve the
      overall structure of the genome.

PMID- 9260515
TI  - Paramutation and related allelic interactions.
AB  - Paramutation is an allelic interaction that results in meiotically heritable
      changes in gene expression. Until recently, the few documented cases in higher
      plants seemed unusual and rare. This perception is rapidly fading because of the
      discovery of related examples and the growing recognition of epigenetic changes
      in a wide variety of biological systems.

PMID- 9260516
TI  - An uncertain silence.
AB  - Transcriptional silencing is the most well-studied epigenetic phenomenon in
      yeast. In Saccharomyces cerevisiae, silencing has recently been found at
      previously unidentified loci. In addition to the silent mating-type loci and
      telomeres, genes within the ribosomal DNA and, perhaps, at undefined aging loci
      are silenced. Efficiency of silencing at different loci varies and is affected by
      competition between the loci and by the involvement of different factors in
      distinct protein complexes. The recent discovery of conserved gene families
      encoding proteins related to modulators of acetylation and deacetylation suggests
      mechanisms for differential regulation of silencing at known loci and the
      existence of additional, as yet undiscovered, silenced loci.

PMID- 9260517
TI  - Chromatin-silencing mechanisms in Drosophila maintain patterns of gene
      expression.
AB  - The Polycomb-Group proteins form chromatin complexes that can silence gene
      expression over large distances. The formation of these complexes at homeotic
      genes depends on early developmental events but the repressed state is then
      maintained through many cell divisions. In vivo, complexes formed at one genomic
      site can interact with those at other sites, suggesting that they, like
      heterochromatin complexes, affect the folding of chromatin and the organization
      of chromosomes in the nucleus.

PMID- 9260518
TI  - DNA methylation and plant development.
AB  - The development of genetic tools to alter DNA methylation has led to a deeper
      understanding of the importance of DNA modification in the life strategies of
      different eukaryotic organisms. This review focuses on recent findings that
      demonstrate a role for cytosine methylation in the development of higher plants.
      The effects of altering DNA modification are considered in the context of unique
      aspects of plant development.

PMID- 9260519
TI  - DNA methylation and imprinting: why bother?
AB  - DNA methylation is crucial for mammalian development because embryos that cannot
      maintain normal methylation levels die after gastrulation. I propose that DNA
      methylation is only important for the somatic lineages, but has no role in
      embryonic lineages including the germ line. Among vertebrates, genomic imprinting
      is found only in mammals, and numerous hypotheses have ascribed an essential
      function to imprinting because of the uniquely mammalian developmental and
      physiological requirements. However, our understanding of molecular details of
      the imprinting process, as well as evolutionary considerations, is rather
      consistent with imprinting having no intrinsic role in mammalian development.

PMID- 9260520
TI  - Imprinting in clusters: lessons from Beckwith-Wiedemann syndrome.
AB  - Imprinted genes in mammals can be clustered in the genome. This raises important
      questions about mechanistic and functional relationships between imprinted genes
      in a cluster. The insulin-like growth factor II (IGF2) gene is paternally
      expressed and is surrounded by maternally expressed genes. Loss of imprinting of
      IGF2 is the most common molecular defect found in the human foetal overgrowth
      syndrome, Beckwith-Wiedemann syndrome (BWS). Transgenic experiments in the mouse
      establish that overexpression of IGF2 can result in most of the symptoms of BWS.
      However, mutations, translocations, or methylation defects in BWS have so far
      been found in three of the linked maternally expressed genes. We present a model
      where the paternal growth enhancer IGF2 is surrounded by multiple maternal
      suppressors, and mutations, or epigenetic alterations, in any of these
      suppressors could cause BWS. In addition, the precise phenotypic spectrum of BWS
      might depend on which maternally expressed gene is mutated.

PMID- 9260521
TI  - Cytosine methylation and the ecology of intragenomic parasites.
AB  - Most of the 5-methylcytosine in mammalian DNA resides in transposons, which are
      specialized intragenomic parasites that represent at least 35% of the genome.
      Transposon promoters are inactive when methylated and, over time, C-->T
      transition mutations at methylated sites destroy many transposons. Apart from
      that subset of genes subject to X inactivation and genomic imprinting, no
      cellular gene in a non-expressing tissue has been proven to be methylated in a
      pattern that prevents transcription. It has become increasingly difficult to hold
      that reversible promoter methylation is commonly involved in developmental gene
      control; instead, suppression of parasitic sequence elements appears to be the
      primary function of cytosine methylation, with crucial secondary roles in allele
      specific gene expression as seen in X inactivation and genomic imprinting.

PMID- 9260522
TI  - Cholera in 1996.
AB  - In 1996, Vibrio cholerae O1 biotype E1 Tor continued to occur in all regions of
      the world (Map 1). The decrease in the number of cases observed since 1994
      continued in 1996, with a total of 143 349 cases and 6689 deaths officially
      reported to WHO. The decrease in the number of cases is not reflected in the
      global case-fatality rate (CFR), which increased to 4.7% compared with 2.4% in
      1995. The number of countries reporting cholera to WHO decreased from 78 in 1995
      to 71 in 1996 (Table 1 and Figs. 1-3). Africa is the continent accounting for the
      largest proportion of all reported cholera cases. The incidence of cholera
      increased by 53%, from 71081 cases in 1995 to 108535 cases in 1996. The CFR in
      Africa reached 5.7%, representing the highest figure in all the regions. The
      Americas reported an important decrease in the number of cases, from 85 809 in
      1995 to 24643 in 1996, i.e. 71%. In Asia, 10 142 cases were reported in 1996, but
      a few countries which reported high incidence rates in 1995 have not yet sent
      their final report to WHO. It is estimated that a decrease of about 30% will be
      observed in Asia once final reports have been received.

PMID- 9260523
TI  - Caring about women, abuse, and inequity.

PMID- 9260524
TI  - Self-reported factors influencing condom use among clinic attendees.
AB  - Data were collected from a convenience sample of 231 urban women seeking health
      care at a Midwestern women's health care center at a city medical center.
      Participants responded to 53 items, most taken from the Family Health Center
      Survey, which was designed to elicit descriptive data related to three major
      categories: background factors, factors that might influence the decision to use
      a condom, and knowledge and attitudes that might predict condom acquisition.
      Knowledge of HIV transmission and safer sex was not a predictor of condom use.
      Through education and demonstrations of proper condom usage, nurses and other
      health care providers were influential in persuading adolescents and young adults
      to use condoms.

PMID- 9260525
TI  - Trauma and addiction experiences of African American women.
AB  - Substance abuse affects African American women at an increasingly alarming rate.
      The interaction of substance abuse and traumatic events requires exploration. For
      many African American women, early life trauma plays a critical role in how and
      when they fall victim to the ravages of substance abuse. This article about a
      phenomenological study of 15 African American women uses intense narratives to
      disclose experiences of incest, rape, abuse, and other horrors that led to drug
      and alcohol use to extinguish pain. The themes include family history of
      substance abuse, lack of a caring childhood environment, pain resulting from
      trauma, and coping and recovery. The womens' stories provide insights for nurses
      in practice and research related to the psychosocial health of women.

PMID- 9260527
TI  - Patterns of violence in homeless women.
AB  - Fifty percent of all women in America have reported being battered at some point
      in time, and one in five report regular assaults. This exploratory qualitative
      study's purpose was to describe reported patterns of violence in sheltered
      battered women. Homelessness was the adaptive response to battering. A purposive
      sample of 7 women described violence patterns from childhood and their most
      recent relationships prior to seeking shelter. In-depth audiotaped interviews
      indicated extreme violence and terror. Thematic analysis revealed an
      understanding of abusive patterns with a male partner. A theory of freedom
      seeking behavior emerged, with related themes including terror, murderous
      thoughts, awakening, and escape. The emerging theory has implications for
      outreach, case finding, and identification of intervention timing for abused
      women.

PMID- 9260526
TI  - HIV risk behaviors become survival techniques for aboriginal women.
AB  - In northern Alberta, the Aboriginal (native) female population appears to be
      overrepresented in the HIV statistics. A qualitative research study was designed
      to explore the cultural factors that relate to the high HIV infection rate in
      these women. Eight HIV-positive women were interviewed for the study,
      representing about one third of the population. A model was developed to explain
      the relationships that exist between the women's formative years, their self
      esteem, and the survival techniques they used prior to becoming HIV-positive.
      These survival techniques may have placed them in situations that increased their
      risk of infection with the HIV virus.

PMID- 9260528
TI  - Past childhood experiences and current parent-infant interactions.
AB  - To examine the relationships between adults' childhood experiences in their
      family of origin, current level of marital support, and quality of parenting
      interactions, 66 mothers and fathers were observed individually interacting with
      their infants during home visits using a standardized observational measure
      (Nursing Child Assessment Teaching Scale). Parents completed questionnaires on
      marital support (Dyadic Adjustment Scale) and on childhood experiences in the
      family of origin (Parental Acceptance-Rejection Questionnaire). For mothers,
      there was no relationship between childhood experiences and the quality of
      parenting interactions. For fathers, the relationship varied as a function of
      marital support. Fathers who perceived less positive childhood experiences but
      who had more optimal levels of marital support were predicted to have more
      responsive parenting interactions.

PMID- 9260529
TI  - An oral contraceptive perception scale for female adolescents.
AB  - This study sought to develop the initial psychometric properties of a female
      adolescent oral contraceptive perception scale. Based on qualitative data, a 39
      item scale of perceived benefits and barriers was developed, reviewed by
      adolescence experts and adolescents, and voluntarily completed by 407 female
      adolescents enrolled in family planning clinics. After item analysis, 15 items
      were deleted. Maximum likelihood factor analysis with varimax rotation yielded
      two barrier (relationship-oriented and oral contraceptive regimen) and four
      benefit (relationship-oriented, pregnancy prevention related to self, pregnancy
      prevention related to others, personal responsibility) factors that accounted for
      53% of the variance. The scale had acceptable reliability (alpha coefficients
      ranged from 0.71 to 0.87). The scale should be beneficial to further research in
      this area.

PMID- 9260530
TI  - Unanticipated results of continuity of care research with the elderly, Part 2-
      Health system issues.

PMID- 9260531
TI  - Feeding infants, invalids, and the infirm.

PMID- 9260532
TI  - Dengue haemorrhagic fever/dengue shock syndrome. An unwelcome arrival in
      Trinidad.
AB  - This is the first report of dengue haemorrhagic fever and dengue shock syndrome
      in Trinidad. Dengue infection was confirmed serologically or by viral isolation
      in five patients, aged 15 to 53 years, who presented with fever, thrombocytopenia
      and haemoconcentration. Three patients developed dengue shock syndrome, which was
      fatal; although there was no haemorrhagic tendency among these patients, bleeding
      occurred shortly before death in one of them. Two patients who had dengue
      haemorrhagic fever survived. The co-circulation of dengue virus serotypes 1, 2,
      and 4 in the Caribbean facilitates the development of dengue shock syndrome (DSS)
      or dengue haemorrhagic fever (DHF). Clinicians should therefore be aware of their
      clinical features, laboratory diagnosis and clinical management. Appropriate
      public health interventions and improved surveillance should be implemented to
      reduce the risk of DHF/DSS associated mortality in Trinidad and Tobago.

PMID- 9260533
TI  - Survey of patients with sexually transmitted diseases seen by private physicians
      in Jamaica.
AB  - A survey of physicians in private practice in Jamaica was conducted between March
      and September 1993 to provide a descriptive analysis of the occurrence of
      patients with sexually transmitted diseases (STDs) seen in their practices.
      Questionnaires were delivered to 371 physicians of whom 127 (34%) responded,
      completing 683 (men 353, women 330) individual patient questionnaires. Each
      physician collected data over a period of one week. The median ages of the men
      and women were 27 years and 26 years, respectively. 464 (68%) patients were being
      seen for the first time for symptomatic STDs, and the visit was a follow-up for
      132 (19%) who had been previously diagnosed; 40 (6%) patients were asymptomatic
      contacts referred by a sex partner, and 12 (2%), who were asymptomatic, asked for
      a 'checkup'. A history of previous STD was given by 358 (52%) patients. 470 (69%)
      patients had a genital discharge (M, 65%; F, 73%; p = 0.017), 52 (8%) had
      anogenital lesions (M, 10%; F, 5%; p = 0.013) and 45 (7%), inguinal
      lymphadenopathy (M, 10%; F, 3%; p = 0.002). Among women, 131 (40%) had lower
      abdominal pain on examination and 105 (32%) had cervical excitation tenderness or
      pain suggesting pelvic inflammatory disease (PID). A working diagnosis of
      gonorrhoea was made in 273 (40%) patients, trichomoniasis in 121 (18%),
      nongonococcal infection in 114 (17%), syphilis in 60 (9%), herpes genitalis in 20
      (3%) and chancroid in 11 (2%). PID was diagnosed in 121 (37%) women and
      nongonococcal urethritis in 98 (28%) men. The most frequently prescribed
      treatments were for chlamydia, gonorrhoea and trichomoniasis. In general, working
      diagnoses correlate well with clinical observations and treatment given, matched
      with diagnosis according to national guidelines. A comparison of the STD burden
      between the public and private sectors was not possible because of sample bias.

PMID- 9260534
TI  - Lipids, apolipoprotein-E genotypes and other risk factors of patients with
      coronary artery disease in Curacao.
AB  - We studied lipids, apolipoprotein-E (apo-epsilon) genotypes and other coronary
      artery disease (CAD) risk factors of 67 CAD patients (male/female ratio 5) in
      Curacao. Compared with 57 controls, male CAD patients had higher cholesterol,
      triglycerides, LDL-cholesterol, apo-B and decreased HDL-cholesterol and HDL
      cholesterol/cholesterol concentrations. Other CAD risk factors were: increased
      fasting glucose and HbA1c concentrations, decreased creatinine clearance, and
      increased prevalences of lipoprotein (a) concentration > 500 mg/l, renal disease,
      hyperhomocysteinaemia, diabetes mellitus type II (DM-II), positive CAD family
      history and cigarette smoking. Male CAD patients had higher plasma alpha
      tocopheroleq. Compared with 29 female controls, female CAD patients had higher
      fasting plasma glucose and HbA1c concentrations, and prevalence of DM-II.
      Predicting factors for CAD development in the whole CAD group were: DM-II,
      cigarette smoking, apo-epsilon 3/epsilon 4 and apo-epsilon 4/epsilon 4 Apo
      epsilon 4 was associated with lower HDL- and higher LDL-cholesterol
      concentrations. There is a need for local studies on improvement of diabetic
      control, reference values of lipoprotein (a) and homocysteine concentrations, on
      apolipoprotein (a) phenotypes, causes of hyperhomocysteinaemia, and dietary
      influences on CAD development in subjects who carry the apo-epsilon 4 allele.

PMID- 9260535
TI  - The dietary fatty acids of patients with coronary artery disease and controls in
      Curacao. Implications for primary and secondary prevention.
AB  - Patients with coronary artery disease are advised to augment their dietary
      linoleic acid intakes at the expense of saturated fatty acids. We investigated
      whether the dietary linoleic acid intake of 57 patients with coronary artery
      disease (47 males, 10 females; ages 61 +/- 10 years) in Curacao is higher as
      compared with 77 controls (51 males, 26 females; ages 56 +/- 7 years). For this,
      we measured plasma cholesterol ester fatty acids, which reflect the dietary fatty
      acid composition of the preceding weeks. Patients with coronary artery disease
      and controls had minor differences in cholesterol ester fatty acids. Their
      cholesterol ester linoleic acid content suggests that the dietary
      polyunsaturated/saturated fatty acid ratio is far below 1. Comparison with data
      reported for The Netherlands, Greenland and Crete showed that the dietary fatty
      acid composition in Curacao is typically Western with a high intake of saturated
      fatty acids, a low intake of monounsaturated fatty acids and the consumption of
      linoleic acid as the predominant polyunsaturated fatty acid. Intake of long chain
      polyunsaturated fatty acids from fatty fish is low. Reduction of dietary
      saturated fatty acids, augmentation of fish consumption, and an increase of the
      alpha-linolenic/linoleic acid ratio are likely to be of benefit to both primary
      and secondary prevention from coronary artery disease in Curacao.

PMID- 9260536
TI  - Urea kinetic modelling in two groups of patients on continuous ambulatory
      peritoneal dialysis.
AB  - Dialysis adequacy (Kt/V) was investigated in two groups of patients on continuous
      ambulatory peritoneal dialysis (CAPD). Group I consisted of patients with serum
      creatinine concentration above 1200 mumol/l and Group II comprised patients with
      serum creatinine concentration of 600 mumol/l and less. The mean Kt/V was
      significantly higher in Group II (Kt/V, 2.0) than in Group I (Kt/V, 1.59; p <
      0.01) patients. The mean duration of CAPD was significantly longer in Group I
      (3.12 years) than in Group II (1.32 years; (p < 0.01) patients, and the mean
      total creatinine clearance for Group II patients was significantly higher than
      for Group I (p < 0.001) patients. There was good correlation between Kt/V and
      total creatinine clearance (r = 0.73; p < 0.001); and between Kt/V and normalized
      protein catabolic rate (NPCR, r = 0.6; p < 0.001). There was weak correlation
      between Kt/V and duration on dialysis, but this was statistically significant.
      There was no significant difference between mean NPCR and mean mid-arm muscle
      circumference (MAMC) in the two groups and no significant association between
      Kt/V and dietary inventory. Group II patients had a significantly better residual
      renal clearance (p < 0.0001). Pruritus was a troublesome feature in Group I
      patients but in both groups patients were distressed by loss of libido, insomnia
      and tiredness. This study revealed that Group II patients with lower creatinine
      concentrations had better dialysis adequacy but were on CAPD for a shorter
      duration than Group I and had significantly better residual renal clearance and
      total clearance. Muscle mass does not appear to have contributed significantly to
      the differences in creatinine concentration between the groups. Additional
      studies on peritoneal membrane function vis-a-vis solute transfer are in
      progress.

PMID- 9260537
TI  - Hepatic cirrhosis in Jamaica.
AB  - The aetiology, biochemistry, clinical features and complications of
      histologically confirmed hepatic cirrhosis in 45 patients (26 females, 19 males)
      seen at the University Hospital of the West Indies, Jamaica, between 1984 and
      1994 are presented. The age range was 1 to 72 years (mean 48 years). Abdominal
      swelling and weight loss were the commonest symptoms, occurring in 51% and 47% of
      patients, respectively. Jaundice was a presenting feature in 44%. Hepatomegaly
      was present in 71% of patients and splenomegaly in 33%. The aetiological factors
      were: alcohol (36%), bush tea (18%), chronic active hepatitis (11%), drugs (7%),
      and haemochromatosis (2%). Hepatitis B surface antigen was detected in 2 of 20
      patients tested. 24% of the patients also had diabetes mellitus., 29% were
      anaemic, 29% were thrombocytopenic, 4% were leukopenic, and the prothrombin time
      was prolonged in 22%. The albumin/globulin ratio was reversed in 71% of the
      patients. The alkaline phosphatase was elevated in 56%, the aspartate
      aminotransferase was increased in 58% and the gamma glutamyl transpeptidase in
      56%. 56% of the patients had macronodular cirrhosis; the liver showed a
      micronodular pattern in 18%; 7% had biliary cirrhosis; 7% chronic active
      hepatitis with cirrhosis; and 13% showed a mixed macro-micronodular pattern.
      Ascites and fluid overload developed in 44% of the patients. Hepatic
      encephalopathy occurred in 18% and upper gastrointestinal bleeding in 18%.

PMID- 9260538
TI  - Thyrotoxic vomiting. A case report.
AB  - A post menopausal female with severe vomiting and weight loss in association with
      elevated thyroid hormone levels is presented. Signs and symptoms of
      thyrotoxicosis were not evident at presentation. Possible pathophysiological
      mechanisms and treatment are discussed. Antithyroid therapy with carbimazole and
      propranolol induced rapid resolution of her symptoms and marked improvement in
      well-being. Radioactive iodine ablation of her thyroid gland was performed later
      and she has remained asymptomatic.

PMID- 9260539
TI  - Whitefly (Hemiptera: Aleyrodidae) binding site for imidacloprid and related
      insecticides: a putative nicotinic acetylcholine receptor.
AB  - Imidacloprid is used extensively to control sweetpotato whiteflies, Bemisia
      argentifolii Bellows & Perring [also known as B. tabaci (Gennadius) biotype B].
      As a radioligand, [3H]imidacloprid binds rapidly to a single class of high
      affinity sites in membrane preparations from whole adult whiteflies with an
      apparent dissociation constant of 2 nM and maximal binding capacity of 101
      fmol/mg protein. Three related compounds (the nitromethylene analog of
      imidacloprid, acetamiprid, and nitenpyram) inhibit [3H]imidacloprid binding by
      50% at 0.40, 2.9, and 57 nM, respectively. The pharmacological profile of the
      binding site (examined with imidacloprid and the analogs listed above, and
      nicotine, alpha-bungarotoxin, carbachol, acetylcholine [with paraoxon], and
      atropine) is consistent with that anticipated for a nicotinic acetylcholine
      receptor and correlates well with binding results for house fly, Musca domestica
      L., head membranes under the same conditions. Thus, [3H]imidacloprid is a
      suitable radioligand to investigate the putative nicotinic acetylcholine receptor
      of Bemisia and the possible modifications of this target site associated with
      selection of resistant strains.

PMID- 9260540
TI  - Insecticidal activity of monoterpenoids to western corn rootworm (Coleoptera:
      Chrysomelidae), twospotted spider mite (Acari: Tetranychidae), and house fly
      (Diptera: Muscidae).
AB  - Acute toxicities of 34 naturally occurring monoterpenoids were evaluated against
      3 important arthropod pest species; the larva of the western corn rootworm,
      Diabrotica virgifera virgifera LeConte; the adult of the twospotted spider mite.
      Tetranychus urticae Koch; and the adult house fly. Musca domestica L. Potential
      larvicidal or acaricidal activities of each monoterpenoid were determined by
      topical application, leaf-dip method, soil bioassay, and greenhouse pot tests.
      Phytotoxicity was also tested on a corn plant. Citronellic acid and thymol were
      the most topically toxic against the house fly, and citronellol and thujone were
      the most effective on the western corn rootworm. Most of the monoterpenoids were
      lethal to the twospotted spider mite at high concentrations; carvomenthenol and
      terpinen-4-ol were especially effective. A wide range of monoterpenoids showed
      some larvicidal activity against the western corn rootworm in the soil bioassay.
      Perillaldehyde, the most toxic (LC50 = 3 micrograms/g) in soil, was only 1/3 as
      toxic as carbofuran, a commercial soil insecticide (LC50 = 1 microgram/g).
      Selected monoterpenoids also effectively protected corn roots from attack by the
      western corn rootworm larvae under greenhouse conditions. alpha-Terpineol was the
      best monoterpenoid in the greenhouse pot test. The acute toxicity of
      monoterpenoids was low relative to conventional insecticides. Some monoterpenoids
      were phytotoxic to corn roots and leaves. l-Carvone was the most phytotoxic,
      whereas pulegone was the safest. The results with thymyl ethyl ether, one of the
      synthetic derivatives of thymol, showed a potential of derivatization to reduce
      monoterpenoid phytotoxicity.

PMID- 9260541
TI  - Differential susceptibility of Dysmicoccus vaccinii (Homoptera: Pseudococcidae)
      to entomopathogenic nematodes (Rhabditida: Heterorhabditidae and
      Steinernematidae).
AB  - The susceptibility of the mealy bug, Dysmicoccus vaccinii Miller & Polavarapu, to
      infection by various species and strains of entomopathogenic nematodes was
      investigated in laboratory sand-dish and sand-column assays. Steinernemo
      carpocapsae (Weiser) (All strain), S. feltiae (Filipjev) (AB [Australia] strain),
      and S. glaseri (Steiner) (NC strain) were ineffective against individual
      mealybugs in sand-dish assays conducted in small petri dishes (1 cm high by 3.5
      cm diameter) at 25 degrees C with doses of infective juvenile nematodes ranging
      up to 500 or 1,000 infective juveniles and exposure periods up to 5 d. However,
      Heterorhabditis bacteriophora Poinar (HP88 strain and 2 New Jersey isolates). H.
      hawaiiensis Gardner, Stock & Kaya (MG-13 strain), and H. indicus Poinar,
      Karunakar & David (EMS-13 strain) induced significant mortality (65.0-90.0%) at
      doses as low as 100 infective juveniles and an exposure of 5 d. H. bacteriophora
      (HBNJ strain) was effective at doses of 500 and 1,000 infective juveniles but,
      together with H. zealandica Poinar (V16 strain) and 4 other H. bacteriophora
      isolates from New Jersey, was ineffective at doses of 100 infective juveniles.
      Removal of the waxy coating from the mealybugs did not influence susceptibility
      to H. bacteriophora (HP88 strain). In the sand-column assay (5.5 cm high by 5 cm
      diameter, 5-d exposure, 25 degrees C), which more closely resembles host-finding
      in the field, H. bacteriophora (HP88 strain) induced no significant mortality
      against individual mealybugs at doses of 100 infective juveniles but produced
      93.8% mortality at 500 infective juveniles, whereas H. indicus (EMS-13 strain)
      induced 56.3 and 100% mortality at 100 and 500 infective juveniles, respectively.
      H. bacteriophora (HP88 strain and some New Jersey isolates), H. hawaiiensis (MG
      13 strain), and H. indicus (EMS-13 strain) successfully reproduced in and emerged
      from mealybug cadavers. This study demonstrates strong variability in the
      susceptibility of D. vaccinii to different species and strains of
      entomopathogenic nematodes, and implicates certain heterorhabditids as promising
      candidates for the biological control of this insect.

PMID- 9260542
TI  - Clinical study of alar anatomy and surgery of the alar base.
AB  - OBJECTIVES: To analyze and quantify specific aspects of alar base anatomy and to
      identify anatomic configurations that may be correlated with specific surgical
      manipulations. DESIGN: Analysis in a population of patients presenting for
      aesthetic nasal surgery. SETTING: Facial plastic surgery practice. PATIENTS: The
      photographic slides of 120 white patients who presented for consultation were
      reviewed. INTERVENTIONS: On the base view of photographic slides, observations
      were made on the width of the alar base, recurvature of the alar base, thickness
      of the alar lobule, thickness of the alar wall, and flare of the alar wall. On
      the lateral view, observations were made on the vertical insertion of the ala on
      the face (cephalic, normal, or caudal), contour of alar rim in profile (gentle S
      shape or straight), size of alar lobule (small, normal, or large), and alar
      columellar relationship, with special attention to the presence of alar hooding.
      MAIN OUTCOME MEASURES: A spreadsheet program was used to analyze the incidence of
      each configuration and any association between various features of the alar base.
      RESULTS: Anatomic diversity exists that requires a careful individual analysis
      for each patient. A planned surgical intervention must fit the patient's unique
      anatomy. Distinctive configurations of recurvature, vertical insertion, and other
      aspects of the alar base were observed, with special implications for the
      surgeon's approach. CONCLUSIONS: Anatomic diversity requires a thorough
      preoperative examination followed by selection of an approach that addresses the
      specific anatomic findings. The choice of the best alar reduction and sculpture
      technique ultimately relies on a precise analysis of the anatomic configuration
      of the patient's alar base.

PMID- 9260543
TI  - Use of alar batten grafts for correction of nasal valve collapse.
AB  - OBJECTIVE: To determine the efficacy of alar batten grafts for the correction of
      internal and external nasal valve collapse. DESIGN: In this retrospective study,
      a questionnaire was used to ask patients to rate their nasal breathing before and
      after application of alar batten grafts. SETTING: Private practice and academic
      tertiary referral medical center. PATIENTS: The questionnaire was given to 63
      patients who underwent application of alar batten grafts between 1980 and 1995.
      Forty-six patients (73%) responded and were included in the study. INTERVENTION:
      Alar batten grafts were applied into a precise pocket via a limited endonasal
      incision or via the external rhinoplasty approach. The grafts consisted of curved
      septal cartilage or auricular cartilage and were applied to the site of maximal
      lateral nasal wall collapse. The convex surface of the cartilage was oriented
      laterally to allow maximal lateralization of the collapsed portion of the lateral
      nasal wall. In most cases, alar batten grafts were applied caudal to the existing
      lateral crura and extended from the lateral one third of the lateral crura to the
      piriform aperture. OUTCOME MEASURES: The degree of nasal airway obstruction was
      determined by subjective scoring on a scale from 1 (no obstruction) to 5
      (complete obstruction) before and after surgery. The patency of the internal
      airway was also assessed on physical examination. RESULTS: The results of the
      study revealed that all but 1 of the 46 patients experienced an improvement in
      their nasal airway obstruction. The mean improvement in nasal airway obstruction
      was 2.5 on a scale of 5. Patients that had the least improvement had intranasal
      scarring in the region of the internal nasal valve, loss of vestibular skin, or
      excessive narrowing at the piriform aperture. Physical examination revealed a
      significant increase in the size of the aperture at the internal or external
      nasal valve after the application of the alar batten grafts. There was minimal
      postoperative fullness in the supraalar region, where the alar batten grafts were
      applied. With time, this fullness decreased, leaving little evidence of the graft
      and an overall improvement in the aesthetic result. CONCLUSIONS: Alar batten
      grafts are effective for long-term correction of internal and external nasal
      valve collapse that is not complicated by intranasal scarring in the region of
      the nasal valve, loss of vestibular skin, or excessive narrowing at the piriform
      aperture.

PMID- 9260544
TI  - Lipogranulomas as complications of septorhinoplasty.
AB  - BACKGROUND: Nasal tumors caused by lipogranulomas are a rare complication of a
      rhinoplasty; only 1 report of this occurrence was found in the literature.
      OBJECTIVE: To present a series of 4 patients with subcutaneous nasal tumors after
      each had undergone a rhinoplasty, together with a review of the literature and
      the clinical consequences. DESIGN: Case series. SETTING: Hospitalized care at a
      university ear, nose, and throat department. PATIENTS: Four patients were
      referred within 6 months from a single department for consultation because of
      broad nasal pyramids after each patient had undergone a rhinoplasty. The origin
      of the deformities was not known. INTERVENTIONS: Ear, nose, and throat and
      ultrasound examinations and computed tomography (ie, bone and soft tissue
      examinations). Two patients had undergone revision surgery and histological
      examinations of subcutaneous fibrous tissue. MAIN OUTCOME MEASURE: Search for the
      origin of the nasal deformity. RESULTS: All 4 patients had wide nasal pyramids.
      One of the 4 patients also had subcutaneous tumors of the nasal dorsum, glabella,
      and medial canthus area; this patient had subcutaneous cystic lesions on computed
      tomography and ultrasound examination and a foreign body reaction around "empty
      spaces" on histological examination. The tumorlike lesions were the result of
      displaced ointment from the endonasal packings. Two of the 4 patients with minor
      deformities did not undergo any surgical revision, and they still had some
      moderate reduction of the cystic lesions within 1 year after the rhinoplasty.
      CONCLUSIONS: Lipogranulomas caused by ointments that are used together with nasal
      packings are most often reported in the orbit after endonasal sinus surgery. The
      incidence should be more frequent in patients who undergo a rhinoplasty because
      connections between the endonasal cavity and the extranasal subcutaneous layer
      are created routinely by osteotomies or removal of a hump. Thus, postoperative
      deformities (eg, inadequate narrowing of the bony pyramid or supratip thickening
      [permanent swelling of the nasal tip]) should be examined by use of computed
      tomography, if lipid ointments were used endonasally. For prevention, no lipid
      substances should be applied together with pressure from packings. In the case of
      a lipogranuloma, surgical removal via an open approach is the treatment of
      choice.

PMID- 9260545
TI  - Endoscopic excision of a forehead mass.
AB  - Endoscopic applications in facial plastic surgery have recently increased with
      the advent of new instrumentation and as surgeons have become more accustomed to
      their use. We report the first case (to our knowledge) of an endoscopic removal
      of a forehead soft tissue mass. The endoscopic approach allows the surgeon access
      to the forehead area with placement of a skin incision in the hair-bearing scalp.
      This type of approach is especially of value in patients with a predisposition to
      unusual scar formation or in those with smooth skin in which a direct incision
      would yield a noticeable scar.

PMID- 9260546
TI  - Distortion of the auriculocephalic angle following rhytidectomy. Recognition and
      prevention.
AB  - Distortion of ear protrusion after rhytidectomy results in an aesthetically
      unfavorable appearance. We have seen cases in which the auriculocephalic angle
      has widened postoperatively, producing a noticeable deformity. Herein, we report
      3 cases that resulted in abnormal postsurgical ear protrusion. We also discuss
      prevention through the use of conchal setback sutures.

PMID- 9260547
TI  - Intraoperative mapping of sensate flaps. Electrophysiologic techniques and
      neurosomal boundaries.
AB  - BACKGROUND: The desirability of restoring sensation to the upper aerodigestive
      tract has led to an expanded use of sensate flaps for reconstruction of mucosal
      defects. Sensation can be restored via preformed neural pathways through the
      anastomosis of recipient and donor nerves, provided that the sensate flap falls
      within the boundaries of the neurosome for the identified sensory nerve.
      OBJECTIVES: To perform detailed electrophysiologic mappings of neurosomes of
      potential sensate flap donor sites, to describe their variability, and to
      investigate the usefulness of intraoperative mapping in terms of flap design and
      harvesting. DESIGN: A case series of 27 patients who were undergoing free flap
      reconstruction of various postablative head and neck defects were examined. Two
      silver-silver chloride recording electrodes were placed in direct contact with
      the dissected sensory nerve, and the overlying skin was either mechanically or
      electrically stimulated. Auditory feedback, as well as visualization of the
      responses on an oscilloscope, determined whether the stimulated area fell within
      the neurosome. This technique was applied to the lateral antebrachial cutaneous
      nerve of the radial forearm flap (n = 15), the lateral sural cutaneous nerve of
      the fibula flap (n = 5), the subcostal nerve of the iliac crest flap (n = 6), and
      the dorsal cutaneous rami of spinal nerve T-1 or T-2 of the scapula flap (n = 1).
      RESULTS: The neurosome of the lateral antebrachial cutaneous nerve was relatively
      consistent with the variability only at the distal boundary (ie, the dorsum of
      the hand). The neurosome of the lateral sural cutaneous nerve was more variable,
      falling into 2 distinct innervation patterns: one showing innervation that was
      limited to the upper lateral and posterior portions of the calf and the other
      demonstrating significant extension into the lower half of the calf. The
      neurosome of the subcostal nerve showed little variability and consistently
      overlapped the proposed skin paddle. The neurosome of the T-1 or T-2 spinal nerve
      was mapped in 1 patient and is described. CONCLUSIONS: The consistency of
      neurosomal boundaries is dependent on the donor site. Intraoperative mapping of
      flap donor sites may not only assure the harvesting of a true sensate flap, but
      may also allow for intraoperative decision making with regard to possible
      modifications of flap design and harvesting techniques. Two new sensate flaps
      from the iliac crest and scapula are accurately described.

PMID- 9260548
TI  - Lateral arm microvascular flap in head and neck reconstruction.
AB  - OBJECTIVES: To report our results of a study of 28 patients who underwent
      sequential reconstructions of the head and neck using the lateral arm flap. To
      discuss the situations where we have found the procedure useful, report the
      complication rates, and delineate the advantages and disadvantages of using this
      flap. DESIGN: A clinical series of patients was followed up prospectively. The
      swallowing function of a subgroup that underwent oropharyngeal reconstruction was
      compared with that of a simultaneous control group that underwent reconstruction
      with the pectoralis major flap. SETTING: University medical center. PARTICIPANTS:
      Patients with malignant neoplasms of the head and neck who underwent resections
      and reconstruction with the lateral arm flap. INTERVENTIONS: Twenty-eight
      patients underwent head and neck reconstruction using lateral arm flaps. In 17
      patients, the lateral arm flaps were used for pharyngeal and posterior oral
      cavity defects. Thirteen of these patients underwent reinnervation. Nine combined
      palatal and midfacial defects were reconstructed, and 1 lateral facial defect was
      reconstructed. Most cases were advanced malignant neoplasms and represented a
      selected minority of similar resections performed at our institutions. Three
      maxillary reconstructions were performed secondarily. All other reconstructions
      were performed at the time of tumor ablation. MAIN OUTCOME MEASURES: Data were
      collected regarding flap survival, return of sensation in flaps, complication
      rates, and the ability to feed orally. RESULTS: All flaps survived in their
      entirety. Of 7.5 tested flaps acquired sensation. Of 14 patients with large
      oropharyngeal defects, 8 resumed early oral feeding and all survivors eventually
      obtained nutrition orally. The ability to swallow was superior to the results
      obtained in a retrospective analysis of a group reconstructed using pectoralis
      major flaps. CONCLUSIONS: A unique feature of this flap is that it incorporates
      both thin skin from the proximal forearm and thicker skin from the upper arm.
      This is ideal for an oropharyngeal defect, where the thin malleable portion can
      be used in the posterior oral cavity or pharyngeal wall and the thicker portion
      in the tongue base. Either portion can be used alone as well. The availability of
      intermediate tissue bulk can also be advantageous for midfacial reconstruction.
      Sensation can be reliably reconstituted with this flap. We think that the lateral
      arm flap is versatile and has particularly low donor-site morbidity.

PMID- 9260549
TI  - Terazosin blockade of nicotine-induced skin flap necrosis in the rat.
AB  - OBJECTIVE: To examine the ability of terazosin hydrochloride to block the
      decrease in skin flap survival induced by nicotine. DESIGN: A randomized
      controlled animal trial. SUBJECTS: Ninety-two male Sprague-Dawley rats were
      randomized to 1 of 5 groups: double-placebo control (n = 15), nicotine opposed by
      oral placebo (n = 26), nicotine opposed by subcutaneous placebo (n = 16),
      nicotine opposed by oral terazosin (n = 21), and nicotine opposed by subcutaneous
      terazosin (n = 14). INTERVENTION: All rats received 1 mg of nicotine twice daily
      via subcutaneous injection except for those in the double-placebo control group,
      which received saline injections twice daily, for the 6-week study. The terazosin
      treatment groups received 1.5 mg of terazosin hydrochloride twice daily either
      orally or subcutaneously while the rest received a saline solution placebo either
      orally or subcutaneously for the last 4 weeks of the study. At the end of the
      fifth week, a 4 x 10-cm, caudally based, dorsal random-pattern flap was elevated
      and repositioned. The outcome was measured in percentage area of flap survival.
      RESULTS: The mean (+/-SEM) area of flap survival for the double-placebo control
      group was 79% +/- 2%. Nicotine opposed by oral placebo or subcutaneous placebo
      produced a significant decrease in survival areas (mean [+/-SEM] area, 73% +/- 2%
      and 74% +/- 2%, respectively). Nicotine opposed by oral terazosin produced a mean
      (+/-SEM) survival area of 81% +/- 2%, which was significantly better than the
      nicotine opposed by placebo group and similar to the control group (P = .02).
      CONCLUSION: Use of oral terazosin elevated flap survival rates to control levels
      in nicotine-treated rats.

PMID- 9260550
TI  - The response of parotid hemangiomas to the use of systemic interferon alfa-2a or
      corticosteroids.
AB  - OBJECTIVE: To evaluate medical treatment for hemangiomas involving the parotid
      area with or without other areas of involvement. DESIGN: Retrospective analysis
      of pediatric patients treated medically for proliferative hemangiomas of the
      parotid region with or without hemangiomas in other regions. Indications for
      treatment included respiratory symptoms relating to hemangiomas of the upper
      airway, difficulty feeding, rapid rate of growth of the hemangioma, and deformity
      or obstruction of the ear canal. SETTING: New York University Multidisciplinary
      Vascular Anomaly Conference, New York, NY, and the Pediatric Oncology Department
      of Ospedale Pediatrico Bambino Gesu, Rome, Italy. PATIENTS: Thirteen patients
      with proliferative hemangiomas in the parotid area were treated medically to
      inhibit growth and enhance involution of the hemangioma. INTERVENTION: Six
      patients were treated with corticosteroids alone (2-4 mg/kg daily). Two patients
      were treated with corticosteroids (2-4 mg/kg daily) followed by interferon alfa
      2a (3 million U/m2 daily) because of a failure to respond to corticosteroid
      therapy. One patient was treated with interferon alfa-2a alone (3 million U/m2
      daily). Four patients were initially treated with interferon alfa-2a, then
      treated with corticosteroids. One of these patients required intralesional
      corticosteroid therapy for a massively enlarged lip and is therefore included in
      this group. The other patient was given oral corticosteroids for unknown reasons
      at another institution. In the remaining 2 patients, there was no response to the
      use of interferon alfa-2a. MAIN OUTCOME MEASURES: The size, bulk, and symptoms
      relating to the hemangiomas of the patients were assessed. RESULTS: None of the
      patients had a significant improvement of the lesions of the parotid hemangiomas.
      In contrast, for those patients with clinical symptoms due to hemangiomas
      elsewhere or with cutaneous involvement typical of hemangiomas, the symptoms
      improved with either of the above therapies, and the cutaneous areas demonstrated
      signs of involution. CONCLUSIONS: The results in the 13 patients in this article
      demonstrate that hemangiomas in certain anatomic sites, such as the parotid area,
      may be more resistant to therapy with corticosteroids or interferon alfa-2a.
      Differences in drug metabolism, caliber of blood vessels, and/or blood flow in
      the parotid gland may account for this observation.

PMID- 9260551
TI  - Effects of sinus surgery on speech.
AB  - OBJECTIVE: To determine the effects of sinus surgery on the production and
      perception of speech. DESIGN: Vocal recordings were performed before, 1 week
      after, and at least 1 month after sinus surgery. Acoustic spectra were analyzed
      for nasal consonants /m/ and /n/, nasalized vowels, and nonnasalized vowels.
      Results for nasal consonants were compared with similar recordings obtained from
      a group of normal subjects with no history of sinus disease. Perceptual analysis
      of nasalized vowels was conducted by trained phoneticians. SETTING: Private
      practice at an academic medical center. SUBJECTS: Five patients who underwent
      endoscopic sinus surgery and 3 normal subjects. MAIN OUTCOME MEASURES: The
      spectral characteristics and perceptual attributes of nasal sounds. RESULTS:
      Significant differences in spectral properties were observed for the consonants
      and nasalized vowels recorded before and after surgery (P < .001). Perceptual
      experiments for nasalized vowels demonstrated a postoperative decrease in
      nasality for the high vowel /i/, as in "beep," and an increase in nasality for
      the non-high vowel /ae/, as in "bad." These perceived changes correlated well
      with acoustic measures of nasal peak amplitudes and the lowest resonance peak
      amplitude of the vocal tract. CONCLUSIONS: Sinus surgery results in measurable
      effects on the produced acoustic signal and the perceived nasality of a patient's
      speech. The identified acoustic correlates may be useful for preoperative
      counseling of patients concerning expected changes in speech quality following
      surgery.

PMID- 9260552
TI  - Inhibition of lymphocyte function by head and neck carcinoma cell line soluble
      factors.
AB  - BACKGROUND: Immunosuppression in patients with head and neck cancer is well
      recognized. Previous investigations have demonstrated graded immunosuppression
      that becomes more pronounced as lymphocyte activity is measured closer to the
      primary neoplasm. In fresh tumors, a soluble factor has been identified that may
      partly account for the observed graded immunosuppression. OBJECTIVE: To examine
      the effect of soluble factors produced by head and neck sqamous cell carcinoma
      cell lines on the generation of lymphokine activated killer cell cytotoxicity and
      peripheral blood lymphocyte proliferation induced by interleukin 2, concanavalin
      A, and phytohemagglutinin. DESIGN: Conditioned supernatant fluids were generated
      in a 4-day incubation period, using 5 head and neck squamous cell carcinoma cell
      lines, and were assayed for the ability to inhibit the generation of lymphokine
      activated killer cell cytotoxicity and naive peripheral blood lymphocyte
      proliferation induced by interleukin 2, concanavalin A, and phytohemagglutinin.
      RESULTS: All conditioned supernatant fluids significantly inhibited the
      generation of lymphokine activated killer cell cytotoxicity relative to controls,
      and this inhibition was dose dependent. In contrast, supernatant fluids from a
      myelogenous leukemic tumor cell line, K562, and an ovarian epithelial cell line,
      SKOV-3, failed to inhibit cytotoxicity. Supernatant fluids conditioned with head
      and neck squamous cell carcinoma cell lines also profoundly inhibited the naive
      peripheral blood lymphocyte proliferation induced by interleukin 2, concanavalin
      A, and phytohemagglutinin. CONCLUSIONS: These studies demonstrate that the cell
      lines of head and neck squamous cell carcinoma produce soluble factors that
      inhibit lymphocyte function. Furthermore, these experiments suggest that the
      inhibition previously observed with enzymatically disaggregated fresh tumors is
      due to factors produced by the tumor cells rather than by other cells within the
      tumor matrix.

PMID- 9260553
TI  - Deletion analysis of the p16/CDKN2 gene in head and neck squamous cell carcinoma
      using quantitative polymerase chain reaction method.
AB  - BACKGROUND: Recently, the p16/CDKN2/MTS1 gene in the 9p21-22 region has been
      offered as a candidate tumor suppressor gene. We examined the frequency of
      hemizygous and homozygous deletions of p16/CDKN2 in head and neck squamous cell
      carcinoma (HNSCC) using a quantitative polymerase chain reaction (PCR) method.
      DESIGN: Twenty-one HNSCC and 12 corresponding normal DNA samples were examined
      for deletion of p16/ CDKN2 using PCR amplification and fluorescent quantification
      of DNA. All tumor and normal DNA samples were also amplified with fluorescein
      labeled primers for a control DNA marker on chromosome 8p (D8S265). The ratios of
      the observed fluorescence of the p16/CDKN2 and 8p PCR products were compared.
      SETTING AND PARTICIPANTS: Patients with HNSCC scheduled to undergo surgical
      resection of their tumors were recruited. After the specimen was removed, a
      portion of the tissue was snap frozen for further DNA extraction. RESULTS: Eight
      tumors (38%) had p16/CDKN2-D8S265 ratios of greater than 0.75; 8 tumors (38%),
      from 0.25 to 0.75; and 5 tumors (24%), of less than 0.25, the average ratio in
      this last group being 0.06. CONCLUSIONS: These ratios suggest a higher rate of
      homozygous deletion than previously reported and significant probable hemizygous
      deletion of the p16/CDKN2 gene in HNSCC.

PMID- 9260554
TI  - Neurotropic cutaneous tumors of the head and neck.
AB  - OBJECTIVE: To determine the outcomes of patients with neurotropic cutaneous
      tumors of the head and neck. DESIGN: A retrospective review was conducted of 7852
      charts of patients who underwent micrographically controlled excisions of skin
      cancers of the head and neck between 1984 and 1995, identifying neurotropic
      tumors and the outcomes of their treatments. SETTING: Tertiary care center
      (university hospital). PATIENTS: Thirty-seven patients with neurotropic tumors
      were identified (and confirmed by secondary histological review), constituting
      0.47% of all patients. The median age at presentation was 68 years and all except
      an albino were white. Nine patients had basal cell carcinomas and 28 had squamous
      cell carcinomas. Twenty-five patients (69%) were referred after at least 1 prior
      excision was performed a median of 16 months previously. INTERVENTION: All
      patients underwent micrographic mapping and excision of the cutaneous portion of
      the tumor. As necessitated by tumor spread, additional soft tissue, skull base,
      and/or intracranial surgery and postoperative irradiation were also conducted.
      MAIN OUTCOME MEASURES: Thirty-four patients (3 patients were unavailable for
      follow-up) were assessed by physician examination a minimum of 19 months after
      treatment (median, 33 months). RESULTS: Of 25 patients with extracranial disease
      only, 19 had no evidence of disease during follow-up and 1 died of intercurrent
      disease at 20 months without evidence of tumor persistence. Of the 9 patients
      with intracranial neurotropic tumors at the time of presentation, 1 remained with
      no evidence of disease, 1 died of intercurrent disease at 21 months without
      evidence of tumor persistence, and the other 7 either died of or are living with
      an intracranial tumor. CONCLUSIONS: Micrographic tissue mapping to detect and
      then encompass neurotropic cutaneous malignancies, along with conventional
      surgery for deeper tumor invasions and irradiation in selected cases, was
      successful in 19 patients (76%) with an extracranial tumor. For those with
      neurotropic tumors approaching or penetrating the skull base, the prognosis was
      poor regardless of therapy method.

PMID- 9260555
TI  - Repair of a complete glottic-subglottic stenosis with a fibular osseocutaneous
      free flap.
AB  - Reconstruction of extensive laryngotracheal stenosis remains a formidable
      challenge. The ideal reconstructive technique has not been found because of the
      variability in the complexity and degree of laryngotracheal stenosis and the
      challenge of wound healing in a contaminated tubular structure. The application
      of microvascular free-tissue transfer in laryngotracheal reconstruction is
      limited. We used a fibula osseocutaneous revascularized flap for reconstruction
      of a complex laryngotracheal stenosis. The clinical course, long-term follow-up,
      and potential advantages and disadvantages are discussed.

PMID- 9260556
TI  - Pathologic quiz case 1. Pneumocystic lymphadenitis.

PMID- 9260557
TI  - Pathologic quiz case 2. Rhabdomyosarcoma (RMS), alveolar type, of the paranasal
      sinus.

PMID- 9260558
TI  - Healing by second intention following Mohs micrographic surgery.
AB  - Healing by second intention is a reconstructive option that is underused by many
      surgeons who treat skin cancers of the head and neck. Deutsch and Becker's
      article in the May issue of the ARCHIVES is a welcome addition to the sparse
      literature on the subject.

PMID- 9260559
TI  - Adjunctive intraoperative photodynamic therapy and microvascular anastomoses.

PMID- 9260560
TI  - Extracellular sodium dismutase: does it have a role in cardiovascular disease?

PMID- 9260561
TI  - Two variants of extracellular-superoxide dismutase: relationship to
      cardiovascular risk factors in an unselected middle-aged population.
AB  - OBJECTIVE: Description of the distribution of plasma levels of two variants of
      extracellular-superoxide dismutase (EC-SOD) and their relationship to
      cardiovascular risk factors in the general population. DESIGN: A cross-sectional
      study. SETTING: Norrbotten and Vasterbotten counties in northern Sweden.
      SUBJECTS: Four thousand, nine hundred 25-74-year-old randomly selected subjects.
      MAIN OUTCOME MEASURES: Plasma levels of EC-SOD. Genotyping by an allele-specific
      PCR method. RESULTS: Plasma EC-SOD levels showed a distinct bimodal distribution
      with the smaller group (3.8%) having a variant of the enzyme with about eight
      fold-higher plasma levels. Genotyping was performed in 65 individuals with the
      high-level variant. All but one were found to carry the same mutation, Arg213Gly,
      affecting the heparin-binding domain of EC-SOD. Subjects with the high-level
      variant of EC-SOD had modestly higher body mass index and higher levels of serum
      cholesterol, serum triglycerides and plasma fibrinogen than those with the common
      EC-SOD phenotype. Within the population with common EC-SOD, the plasma levels
      were lower in men than in women and increased with age. Low levels of common
      phenotype EC-SOD were associated with smoking, high plasma levels of fibrinogen
      and low activity of tissue plasminogen activator in both univariate and
      multivariate analyses. Obesity and total serum cholesterol were associated with
      high common phenotype EC-SOD levels. CONCLUSIONS: A high-level variant of EC-SOD
      caused by one and the same mutation and with low tissue binding and high plasma
      levels is present in approximately four per cent of an unselected middle-aged
      population in northern Sweden. Plasma levels of EC-SOD may be modulated by
      lifestyle factors such as smoking and show a complex covariation with many of the
      conventional cardiovascular risk factors.

PMID- 9260562
TI  - Infective endocarditis, 1984 through 1993: a clinical and microbiological survey.
AB  - OBJECTIVES: To characterize the epidemiology and the clinical and microbiological
      spectrum of infective endocarditis in a Danish population. DESIGN: A
      retrospective review. SETTING: All episodes hospitalized of infective
      endocarditis from 1984 to 1993 in Viborg County were reviewed. The county is
      served by one general and four local hospitals. SUBJECTS: One hundred and nine
      episodes of suspected infective endocarditis with 62 episodes in 59 patients
      fulfilling the diagnostic criteria by von Reyn. RESULTS: An overall incidence of
      27 episodes per million per year was found. The incidence was 17.4 episodes per
      million per year in the first part of the decade and 36.5 episodes per million
      per year in the second part (P < 0.001). Microscopic haematuria was found in
      70.2% of the patients with infective endocarditis, compared to 16.7% of the
      patients in whom the diagnosis was rejected (P < 0.01). Staphylococcus aureus was
      found in 38.9%, non-beta-haemolytic streptococci in 24.1% and Enterococcus
      faecalis in 16.7%. The overall mortality was 35.5%. The mortality decreased
      significantly from 50.0% in the first part of the decade to 28.6% in the second
      part (P < 0.01). The mortality was 23.1% in patients in whom the diagnosis was
      established whilst they were alive. This finding was significantly lower than the
      overall mortality (P < 0.05). CONCLUSION: The incidence of infective endocarditis
      increased during the decade. The frequency of non-beta-haemolytic streptococci
      was lower than normally reported. Mortality is still high, with the main
      mortality within the first week in hospital, which stresses the importance of
      early case detection and treatment.

PMID- 9260563
TI  - Hyaluronan: its nature, distribution, functions and turnover.
AB  - Hyaluronan is a polysaccharide found in all tissues and body fluids of
      vertebrates as well as in some bacteria. It is a linear polymer of exceptional
      molecular weight, especially abundant in loose connective tissue. Hyaluronan is
      synthesized in the cellular plasma membrane. It exists as a pool associated with
      the cell surface, another bound to other matrix components, and a largely mobile
      pool. A number of proteins, the hyaladherins, specifically recognize the
      hyaluronan structure. Interactions of this kind bind hyaluronan with
      proteoglycans to stabilize the structure of the matrix, and with cell surfaces to
      modify cell behaviour. Because of the striking physicochemical properties of
      hyaluronan solutions, various physiological functions have been assigned to it,
      including lubrication, water homeostasis, filtering effects and regulation of
      plasma protein distribution. In animals and man, the half-life of hyaluronan in
      tissues ranges from less than 1 to several days. It is catabolized by receptor
      mediated endocytosis and lysosomal degradation either locally or after transport
      by lymph to lymph nodes which degrade much of it. The remainder enters the
      general circulation and is removed from blood, with a half-life of 2-5 min,
      mainly by the endothelial cells of the liver sinuoids.

PMID- 9260564
TI  - Hyaluronan in morphogenesis.
AB  - Pericellular matrices surrounding migrating and proliferating cells in the
      developing embryo, in regenerating tissues and in other dynamic cellular events,
      such as tumour cell invasion, are enriched in hyaluronan. In addition to
      contributing to the unique structure of the pericellular matrix, hyaluronan
      interacts with cell surface receptors, such as RHAMM and CD44. During
      morphogenesis, these interactions of hyaluronan with the cell surface are
      important in several ways. First, hyaluronan-CD44 interactions have been shown to
      mediate endocytic removal of hyaluronan at critical stages of embryonic
      development. Secondly, hyaluronan provides an appropriately hydrated,
      pericellular milieu that facilitates cellular invasion. Thirdly, in-vitro studies
      suggest strongly that interactions of hyaluronan with RHAMM or CD44 are involved
      in cell movement and proliferation, which are critical events in morphogenesis.

PMID- 9260565
TI  - Hyaluronan: fundamental principles and applications in cancer.
AB  - Hyaluronan (HYA) plays a particular role in cancer cell microenvironment. A
      component of the desmoplasia. HYA is associated to other macromolecules and
      contributes to the net structure of the matrix. Cancer cells exhibit binding
      sites (CD44, RHAMM) for HYA. The cell adhesion to HYA can influence the cell
      motility and different factors could interplay to facilitate cell detachment from
      HYA. HYA protects cancer cells against immune cell attack. Serum HYA is often
      increased in metastatic patients.

PMID- 9260566
TI  - Dynamic role of hyaluronan (HYA) in connective tissue activation and
      inflammation.
AB  - An increased tissue accumulation of HYA occurs in several human and experimental
      inflammatory conditions. Such is the case in sarcoidosis, idiopathic pulmonary
      fibrosis and farmer's lung in man, and experimental bleomycin-induced lung damage
      in rats. Graft rejection in man and rats, experimental myocarditis in mice and
      myocardial infarction in rats follow the same pattern. Increased amounts of HYA
      also appear in gut luminal perfusion fluid in human inflammatory bowel disease. A
      transient accumulation of HYA is seen in wound healing, which is more sustained
      in fetuses. An increased accumulation of water and presentation of ligands for
      receptors on inflammatory cells are two consequences of the HYA accumulation.

PMID- 9260567
TI  - Hyaluronan in joint disease.
AB  - Hyaluronan is a major component of synovial fluid. It is synthesized in the joint
      and partly degraded in joint capsule and partly carried by lymph to lymph nodes
      and the general circulation. During various joint disorders, especially
      inflammatory ones, the amount of hyaluronan in the joint and its turnover rate
      are increased leading to pathologically high serum levels of the polysaccharide.
      These levels are a complex function of synovitis mass and the physical activity
      of the patient. Intra-articular injection of hyaluronan has been used in the
      treatment of osteoarthritis. Although it results in a relief of pain, controlled
      clinical trials have not yet convincingly shown any beneficiary effects of the
      treatment.

PMID- 9260568
TI  - Hyaluronan in skin.
AB  - Because of the abundance of hyaluronan in skin, interest was early focused on
      variation in the content of the polysaccharide in various pathological conditions
      of this tissue. A large amount of early work utilized histological techniques of
      insufficient specificity but recent developments of specific analytical and
      staining methods for hyaluronan have supplied new data on its presence and
      possible role in skin disorders.

PMID- 9260569
TI  - Is serum hyaluronan a helpful tool in the management of patients with liver
      diseases?
AB  - The results of serial determinations of serum hyaluronan indicate a prognostic
      value in progressive liver damage. In primary biliary cirrhosis and in cirrhotic
      alcoholic liver diseases serum hyaluronan level discriminates between early and
      advanced disease. In alcoholic liver disease serum hyaluronan can be applied as
      assessment of haemodynamic changes. Serum hyaluronan is of use as a non-invasive
      index of liver fibrosis in chronic viral hepatitis. A reversible defect in the
      hyaluronan receptor of the hepatic endothelial cells was suggested following
      studies on paracetamol-induced acute liver damage. In liver transplantation,
      graft function can be predicted by determination of the venous effluent of
      hyaluronan.

PMID- 9260570
TI  - Hyaluronan turnover in relation to infection and sepsis.
AB  - Sepsis is a major clinical problem in intensive care. The mortality in septic
      shock is high, and predominantly due to cardiovascular collapse and multiple
      organ dysfunction. In sepsis high levels of circulating hyaluronan have been
      found, correlating to disease severity and prognosis. The reason behind the
      increased levels could be both decreased hepatic uptake and increased peripheral
      synthesis. Thus, plasma hyaluronan may be a clinically useful marker of hepatic
      dysfunction and possibly also an indicator of the increased inflammatory and
      reparative activity in different organs in septic conditions.

PMID- 9260571
TI  - Pyridoxin-responsive anaemia in a patient with a history of polycythaemia vera.
AB  - Pancytopenia in the course of polycythaemia vera (PV) following the proliferative
      and stable phase, ultimately leads to a spent phase characterized by extensive
      marrow fibrosis. We describe a patient with a history of PV and pancytopenia
      caused by myelodysplasia, before a genuine end stage myelofibrosis had occurred.
      The related anaemia was responsive to pyridoxin.

PMID- 9260572
TI  - Nephrotic syndrome and fibrillary glomerulonephritis.
AB  - A 28-year-old female with cystic fibrosis presented with nephrotic syndrome and
      progressive renal failure. In addition, she complained of blurred vision and
      there was a purpuric skin eruption localized to her legs. A renal biopsy revealed
      fibrillary glomerulonephritis. Skin biopsy demonstrated swelling of capillary
      endothelium, thickening of arteriolar walls and deposition of IgA, C3 and
      fibrinogen by immunofluorescence. Opthalmoscopy and fluorescein angiography
      disclosed cotton wool spots with intraretinal haemorrhages and ischaemia of the
      macula. Albumin infusions resulted in worsening of eye symptoms and signs. The
      presence of these three clinicopathologic entities in a patient with CF may
      indicate the possibility of systemic involvement related to continued exposure to
      chronic bacterial lower lung infection.

PMID- 9260573
TI  - C. perfringens is the most predominantly isolated Clostridial species.

PMID- 9260574
TI  - Severe hyperkalaemia induced by trimethoprim in combination with an angiotensin
      converting enzyme inhibitor in a patient with transplanted lungs.

PMID- 9260576
TI  - Cytotoxic T-lymphocytes recognizing P-glycoprotein in murine multidrug-resistant
      leukemias.
AB  - A multidrug-resistant murine lymphoid leukemia P388/ADR overexpresses P
      glycoprotein (P-gp), an active transporter that pumps cytotoxic drugs out of
      cells and a product of mdr1 gene. Cytotoxic T lymphocytes (CTL) that showed
      cytotoxicity against P388/ADR were generated from mixed lymphocyte tumor cell
      culture. CTL do not kill drugsensitive parental P388 (P388/parent) that does not
      express P-gp. Monoclonal antibody against P-gp inhibited cytotoxic activity.
      Similar results were obtained in another multidrug-resistant cell line P388/VP
      16. Cytotoxic activity was mediated by Thy1+ CD4- CD8+ T-cells. When P388/ADR was
      treated with murine IL-4, expression of P-gp was downregulated. Monoclonal
      antibody against interleukin-4 (IL-4) abrogated the IL-4-induced suppression of P
      gp. Cytolytic activity of CTL against IL-4-treated P388/ADR was dose dependently
      inhibited. These results suggest that P-gp is immunogenic and can be a target of
      CTL in this murine leukemia model.

PMID- 9260575
TI  - Molecular cytogenetics of childhood acute myelogenous leukaemias.
AB  - Chromosome abnormalities of childhood acute myeloblastic leukaemia, observed at
      least in 70-80% of cases, are presently recognized as important parameters for
      diagnostic, prognostic and follow-up purposes. These abnormalities are numerical,
      structural or both numerical and structural. They are also classified in
      "primary" abnormalities, usually more or less related with one subtype of
      leukaemia, and "secondary" abnormalities thought to appear in a second time.
      Chromosome abnormalities of childhood acute myeloblastic leukaemia (AML) are not
      basically qualitatively different from those of adult AML. The main difference
      lies in the incidence of the various types of abnormalities, and these
      differences appear to be more marked for age extremes such as infants and elderly
      patients. In total, 3 common abnormalities are more frequently observed in
      childhood than in adult AML; t(8;21) in AML-M2, monosomy 7 in AML-M4, der(11q) in
      AML-M5. In addition, molecular rearrangements associated with chromosomal
      abnormalities are dependent on the type of rearrangement and not on age. As in
      adult AML, the prognostic value of chromosome abnormalities has been diversely
      evaluated; some anomalies seem to be related to a shorter survival than others
      independent of the various therapeutic protocols used. In the present work,
      chromosome abnormalities of childhood AML have been reviewed according to
      cytologic subtypes as well as to some clinical settings. Special attention has
      been paid to abnormalities frequently or exclusively encountered in children.

PMID- 9260577
TI  - Differential expression of apoptosis, Bcl-x and c-Myc in normal and malignant
      lymphoid tissues.
AB  - Bcl-x and c-Myc have an important role for the immune response by regulating the
      programmed cell death (apoptosis) of lymphocytes. Dysfunction of these selection
      processes can lead to the development of malignant lymphoma. The present study
      aimed at defining the differential expression of apoptosis, Bcl-x and c-Myc in
      normal and in malignant lymphoid tissues. Follicular centre lymphoma (FCL-F) and
      mantle cell lymphoma (MCL) contained the lowest apoptotic indices (AIs), whereas
      Burkitt's lymphoma (BL) had the highest AIs. The AIs correlated significantly
      with the growth rates of the tumours and with the extent of Bcl-x expression. Bcl
      x was expressed in almost all BL cells, but in few tumour cells in FCL-F and in
      MCL. c-Myc, in contrast, was found in the majority of the tumour cells in FCL-F
      and in MCL, but not in BL. Whereas the extent of Bcl-x expression correlated
      positively with the growth rates, an inverse correlation was observed between the
      percentages of c-Myc-positive tumour cells and the growth rates of the tumours.
      We conclude that normal and malignant lymphoid tissues have a distinct pattern of
      apoptosis and that expression of Bcl-x and c-Myc in B cell lymphoma is
      differentially regulated.

PMID- 9260578
TI  - Infradiaphragmatic Hodgkin's disease: the Swedish National Care Programme
      experience. The Swedish Lymphoma Study Group.
AB  - A Swedish national care programme has provided guidelines for staging, treatment
      and follow-up of all patients with Hodgkin's disease (HD) since 1985. Between
      January 1985 and December 1992, 920 patients were reported and followed
      prospectively. Of a total of 533 patients with stage I and II disease, 484
      presented with supradiaphragmatic HD and 49 (9%) with infradiaphragmatic HD. The
      median follow-up time was 4.3 yr (3.3-10 yr). Significant differences in average
      age (45 +/- 21 yr and 55 +/- 19 yr), male:female ratio (1.1:1 and 2.8:1) and B
      symptoms (25% and 47%) were observed in patients with supra- and
      infradiaphragmatic HD, respectively. Forty-six patients with infradiaphragmatic
      HD were treated with a curative intention and 40 (87%) achieved a complete
      response. Eleven (28%) of the 40 patients have recurred and 8 patients have died
      of HD. Complete response rates and recurrence frequencies did not differ from
      those observed in patients with supradiaphragmatic HD. Mortality was, however,
      significantly higher (p = 0.001) in the infradiaphragmatic group; this was due
      mainly to poorer effects of salvage treatment in a elderly population. In this
      population-based study, patients with peripheral disease in stage IA respond well
      to inverted Y irradiation alone, whereas it appears to be important to give stage
      II patients chemotherapy or a combined modality treatment in order to avoid
      unacceptably high recurrence rates.

PMID- 9260579
TI  - Effects of thrombopoietin (c-mpl ligand) on growth of blast cells from patients
      with transient abnormal myelopoiesis and acute myeloblastic leukemia.
AB  - Thrombopoietin (TPO) is a ligand for c-mpl that promotes both proliferation and
      differentiation of megakaryocytes in vivo and in vitro. We investigated the
      expression of c-mpl transcripts and the effects of recombinant human TPO (rhTPO)
      on the proliferation and differentiation of human leukemic cell lines or fresh
      samples obtained from 32 patients with transient abnormal myelopoiesis (TAM) or
      acute myeloblastic leukemia (AML). Cells were cultured with TPO alone or combined
      with rh interleukin-3 (IL-3) or stem cell factor (SCF). Expression of c-mpl was
      verified in 6 of 13 cases tested. All but one of the cases that showed c-mpl
      expression responded to TPO. Blasts from all cases of TAM or French-American
      British (FAB) subtype M7 showed growth responses to TPO with higher sensitivity
      than cells of other FAB subtypes and these responses were increased by addition
      of rhIL-3 or rhSCF in some cases. Responses of cells of other FAB subtypes
      varied. In addition, increased expression of platelet-specific surface antigens
      on MO7E cells after incubation with rhTPO was observed. These data suggest that
      TPO may be involved in the abnormal proliferation and differentiation of human
      leukemic cells, especially of M7 and TAM cells, considered to be of
      megakaryocytic lineage.

PMID- 9260581
TI  - Serum thrombopoietin and interleukin 6 concentrations in tumour patients and
      response to chemotherapy-induced thrombocytopenia.
AB  - The relation between the number of platelets in blood and the concentrations of
      immunoreactive thrombopoietin (TPO), interleukin 6 and interleukin 11 (IL-6, IL
      11) was studied in the sera of 32 normal subjects, of 29 untreated tumour
      patients and of 6 tumour patients following chemotherapy with ifosfamide,
      carboplatin and etoposide (ICE). Platelet counts, TPO and IL-6 concentrations
      were higher than normal in blood of tumour patients before chemotherapy. However,
      no statistical relation existed between these variables. Following chemotherapy,
      the number of circulating platelets decreased reaching a nadir at d 10-13, while
      the serum concentration of TPO increased concomitantly. Circulating IL-6 did not
      increase during chemotherapy-induced thrombocytopenia. IL-11 was not detectable
      in any serum. Thus, the reactive thrombocytosis in tumour patients could be
      related to elevated TPO and IL-6 levels. In contrast to circulating TPO, however,
      neither serum IL-6 nor IL-11 levels increase significantly in thrombocytopenia
      following myelosuppressive. chemotherapy.

PMID- 9260580
TI  - Poor survival in t(8;21) (q22;q22)-associated acute myeloid leukaemia with
      leukocytosis.
AB  - Twenty-nine consecutive cases with a t(8;21)(q22;q22) in the bone marrow (BM)
      karyotype were retrospectively studied concerning clinical, morphological and
      cytogenetic data. All had been diagnosed as acute myeloid leukaemia (AML), 27 FAB
      subtype M2 and two M1, comprising 5% of all cytogenetically analysed AML during
      18 yr. Auer rods were the most consistent t(8;21)-associated morphological
      finding and were demonstrated in 92% of the reviewed BM specimens, whereas BM
      eosinophilia was seen in only 24%. The median age was 53 yr, and 30% of the
      patients were > 60 yr old. Twenty-four patients had received induction
      chemotherapy; 22 of these (91%) entered a complete remission (CR). The median
      survival time in treated patients was 18 months. Leukocytosis at diagnosis (> or
      = 20 x 10(9)/1) was significantly (p = 0.01) associated with shorter survival
      time. All four children are still in first CR after 9-80 months. Seven cases
      (25%) developed granulocytic sarcomas, discovered either at diagnosis (n = 4) or
      at first relapse (n = 3). Secondary chromosome abnormalities were found in 62% of
      the cases, most often loss of a sex chromosome. The presence of such secondary
      aberrations did not correlate with any morphological or clinical characteristics,
      including survival. This first Scandinavian study of AML with t(8;21)
      corroborates the previous findings that these AMLs are characterized by distinct
      morphological features, a high frequency of CR and a striking tendency to develop
      extramedullary leukaemic manifestations. Leukocytosis at diagnosis indicates a
      less favourable prognosis.

PMID- 9260582
TI  - Low-grade primary central nervous system lymphoma in HIV-positive patients:
      report of two cases.

PMID- 9260583
TI  - About the prognostic value of bone marrow histopathological patterns in B-cell
      chronic lymphocytic leukaemia.

PMID- 9260584
TI  - Pulmonary platelet production: physical fragmentation and platelet territories.

PMID- 9260585
TI  - 26th Annual meeting of the International Society for Experimental Hematology.
      Cannes, France, August 24-28, 1997. Abstracts.

PMID- 9260586
TI  - Clinical response versus clinical benefit in oncology: not necessarily equivalent
      terms.

PMID- 9260588
TI  - Induction of apoptotic cell death by direct-current treatment in human leukemic
      cell lines.
AB  - Exposure of human leukemic cell lines (HL-60, ML-1, U-937, MOLT-4, EOL-1) to
      short direct-current (d.c.) treatment induced apoptotic cell death, characterized
      by cell shrinkage and nuclear and internucleosomal DNA fragmentation. On the
      other hand, human peripheral blood lymphocytes and polymorphonuclear cells were
      relatively resistant to d.c. treatment, and did not show any clear nuclear and
      DNA fragmentation. The effect of d.c. was slightly reduced by calcium depletion,
      but was not significantly affected by catalase or by superoxide dismutase. The
      present data suggest that previously reported tumor regression activities of d.c.
      treatment might be due, at least in part, to its apoptosis-inducing activity.

PMID- 9260587
TI  - Regulation of p53 by protein kinase C during multi-stage carcinogenesis.

PMID- 9260589
TI  - Detection of group C adenovirus DNA in small-cell lung cancer with the nested
      polymerase chain reaction.
AB  - Group C adenovirus is latent in human tissues and can malignantly transform
      cells. The purpose of this study was to investigate the association between this
      virus and lung cancer. We investigated latent adenoviral infection using the
      nested polymerase chain reaction and in situ hybridization in transbronchial
      biopsy specimens from patients with small-cell lung cancer and non-small-cell
      lung cancer. The polymerase chain reaction was performed on DNA extracts with two
      sets of primers directed at a 261-base-pair target sequence of the E1A region of
      the adenoviral genome. In situ hybridization was performed on histological
      sections using DNA representing the entire adenovirus type 5 genome. E1A target
      DNA was present in 11 (31%) of 35 cases of small-cell lung cancer but in none of
      the 40 cases of non-small-cell lung cancer (P < 0.01). Of the 11 cases found
      positive by PCR, 8 were positive for adenovirus DNA by in situ hybridization.
      Adenovirus was prominent in tumor cells in 5 of the 8 cases, and in normal
      epithelial cells in the 3 remaining cases. Adenovirus DNA was not detected by in
      situ hybridization in specimens in which E1A DNA was not detected by the
      polymerase chain reaction. Small-cell lung cancer has mutations or deletions in
      the p53 and retinoblastoma genes more frequently than are found in non-small-cell
      lung cancer. Therefore, we speculate that adenovirus infection might participate
      in the pathogenesis of SCLC by producing mutation in these genes, rather than by
      inhibiting the function of these proteins.

PMID- 9260590
TI  - Inhibitory effect of the angiogenesis inhibitor TNP-470 on tumor growth and
      metastasis in nude mice bearing human hepatocellular carcinoma.
AB  - The antitumor and anti-metastatic effects of a potent angiogenesis inhibitor, O
      (chloroacetyl-carbamoyl)fumagillol (TNP-470), was investigated in a highly
      metastatic model of human hepatocellular carcinoma-LCI-D20. Small pieces of LCI
      D20 tumor tissue were implanted subcutaneously into the right axillary region of
      24 nude mice; the mice were then randomized into two groups. To one group, TNP
      470 30 mg/kg was given as a subcutaneous injection every other day from day 1 to
      day 15 and the mice were sacrificed on day 26. An antitumor effect of TNP-470 was
      clearly demonstrated by tumor weight (0.97 +/- 0.34 g compared to 2.04 +/- 0.34
      g, P < 0.001) and alpha-Fetoprotein value (93 +/- 59 micrograms/L compared to 769
      +/- 282 micrograms/L, P < 0.001). There was also an anti-metastatic effect of TNP
      470. Lung metastases developed in only 1 of 12 mice in the treated group, while
      they developed in 6 of mice of the control group. No severe side-effect of TNP
      470 was found in this study. In vitro study revealed that the purified hepatoma
      cells were insensitive to TNP-470 (the 50% inhibitory concentration was 43
      micrograms/ml). These results suggest that the angiogenesis inhibitor TNP-470 has
      both strong antitumor and anti-metastatic effects on a human hepatocellular
      carcinoma model in nude mice.

PMID- 9260591
TI  - p53 gene mutations and expression of p53 and mdm2 proteins in invasive breast
      carcinoma. A comparative analysis with clinico-pathological factors.
AB  - The aim of the study was to analyze p53 gene mutations and the expression of p53
      and mdm2 proteins in 31 randomly selected invasive breast carcinomas. The results
      were then correlated with tumor grade, stage, estrogen receptor status, nodal
      status, and DNA ploidy. The expression of the proteins p53 and mdm2 was
      determined immunohistochemically using formalin-fixed, paraffin-embedded
      material. Screening for p53 mutation involved analysis of the highly conserved
      regions of the p53 gene (exons 5-9) by the polymerase chain reaction/ single
      strand conformation polymorphism (PCR-SSCP) technique. PCR products with band
      shifts were directly sequenced. Immunohistochemical staining of p53 was positive
      in 9 cases (29.0%), only 2 of which showed a p53 gene mutation. These were
      identified as a C-->G transversion at the second position of codon 278 in exon 8
      and an A-->G transition at the second position of codon 205 in exon 6. A third
      case with a mutation was observed (C-->T transition, position 1 of codon 250 in
      exon 7) that did not show p53 immunohistochemically. Of the 9 p53-positive
      tumors, 2 were moderately differentiated (grade II). The remaining tumors were
      poorly differentiated (7/9). By contrast, p53-negative carcinomas were well
      differentiated (grade I) in most cases (P = 0.02). DNA cytometry in 8 of the 9
      p53-positive carcinomas revealed an aneuploid stem line. The majority of the p53
      negative tumors were diploid (P = 0.01). Mdm2 oncoprotein was detected in 10
      tumors (32.2%), 4 of which were p53-positive, including the 3 with mutations. The
      grading of the mdm2-positive tumors was moderate or poor, G1 carcinomas were
      always noted to be mdm2-negative (P = 0.04). Overexpression of p53 protein is a
      complex mechanism and does not merely indicate the detection of mutations in the
      p53 gene. This study has shown that p53 expression correlates with tumor grade
      and DNA ploidy. Mdm2 expression was also associated with the tumor grade.
      Immunohistological demonstration of the p53 protein alone is insufficient as a
      basis for comment on the functional state of the p53 gene and gene product. The
      interrelation between recognition of the p53 protein and gene mutation needs more
      careful assessment to define their roles in the control of neoplasia.

PMID- 9260592
TI  - Apoptosis, proliferative activity and Bcl-2 expression in Epstein-Barr-virus
      positive non-Hodgkin's lymphomas.
AB  - In order to clarify the effects of Epstein-Barr virus (EBV) infection on
      apoptosis and proliferative activity of non-Hodgkin's lymphoma, 135 Japanese
      lymphoma cases were investigated for the presence of viral RNA and its
      correlation with bcl-2 protein (Bcl-2) expression. In addition, the role of EBV
      in lymphoma-genesis was also studied in terms of EBV genotyping and specific
      deletion in the gene for the latent membrane protein 1 (LMP-1). EBER-1 RNA in
      situ hybridization revealed EBV in 18 cases (13.3%), comprising 12 of 44 T cell
      (27.3%) and 6 of 91 B cell (6.6%) lymphomas. Type A EBV was found in all 18 cases
      (100%), and 17 of the 17 (100%) evaluable cases showed a 30-bp deletion within
      the 3' end of LMP-1. Comparison of apoptotic indices (AI), assessed by DNA nick
      end labelling, and proliferative activity, estimated in terms of Ki-67 labelling
      and mitotic indices (KI and MI), demonstrated an overall correlation among AI, KI
      and MI increases in association with Bcl-2 negativity, indicating a close
      relation between apoptosis and proliferation. EBV-positive cases showed
      significantly elevated AI values, independent of Bcl-2 positivity, with no change
      in KI and MI. These results indicate that EBV in Japanese non-Hodgkin's lymphomas
      is exclusively of type A with a specific deletion in LMP-1 and that it tends to
      be present in T cell lymphomas. Moreover, EBV up-regulates apoptosis without any
      relation to Bcl-2 expression and exerts only minor effects on proliferation.

PMID- 9260593
TI  - Concentrations of lysosomal cysteine proteases are decreased in renal cell
      carcinoma compared with normal kidney.
AB  - Renal cell carcinoma contains significantly lower concentrations of the lysosomal
      cysteine proteases, cathepsins B, C, H, L and S, than does normal kidney, as
      shown by several methods, such as activity determination, enzyme-linked
      immunosorbent assay, immunoblotting and immunohistochemistry. The same low levels
      of enzyme activity and concentration have been determined in renal cell carcinoma
      metastases in the lung. Our results on the decreased concentration of cysteine
      peptidases at the protein level would seem to conflict with earlier results on an
      increased concentration of the cathepsin L mRNA in renal cell carcinoma.

PMID- 9260595
TI  - Lung cancer: review of the ECOG experience. Eastern Cooperative Oncology Group.
AB  - Lung cancer represents a major health epidemic worldwide. This article reviews
      some of the recent results of Eastern Cooperative Oncology Group (ECOG) trials in
      this disease.

PMID- 9260594
TI  - Suramin/epidoxorubicin association in hormone-refractory prostate cancer:
      preliminary results of a pilot phase II study.
AB  - PURPOSE: Previous studies indicate that suramin may be an active agent for
      treating hormone-refractory prostate cancer. However, antitumour responses were
      observed in initial experiments only when plasma suramin concentrations were
      maintained in excess of 250 micrograms/ml. Dose-limiting toxicity, especially
      neurological toxicity, is directly related to the duration of exposure and
      sustained plasma drug concentrations of 300 micrograms/ml or more. Combination
      with other agents such as epidoxorubicin, a drug with demonstrable activity in
      metastatic prostatic carcinoma, could be more effective and allow reduced suramin
      doses, while maintaining the suramin antitumor effect; this could make suramin
      therapy more feasible. On the basis of preclinical synergistic activity for
      combined suramin/doxorubicin in prostate cancer cell lines, a pilot study in
      patients with metastatic hormone refractory prostate cancer was performed.
      MATERIALS AND METHODS: Ten patients with hormone-refractory prostate cancer
      received a fixed dosing scheme of suramin infusion in combination with weekly
      epidoxorubicin at 25 mg/m2. Therapy was discontinued for dose-limiting toxicity
      or progressive disease. RESULTS: None of the ten patients achieved a prostate
      specific antigen reduction of more than 50% and no objective responses were
      observed in any patient. Dose-limiting toxicity was observed in four patients:
      grade 3 neurotoxicity was observed in three patients and grade 3 nephrotoxicity
      in one patient. CONCLUSIONS: Suramin/epidoxorubicin association, despite the
      encouraging preclinical results, was not able to improve the antitumour activity
      of suramin and showed significant toxicity. The results achieved in our study,
      although in a small number of patients, seem to suggest that this regimen cannot
      be recommended for use in the treatment of metastatic hormone-refractory prostate
      cancer.

PMID- 9260597
TI  - First-line chemotherapy of advanced breast cancer with a combination of
      mitoxantrone, methotrexate, and vincristine (MIMO).
AB  - Fifty-one patients with advanced breast cancer entered a prospective study of
      combination chemotherapy, consisting of mitoxantrone (10 mg/m2), methotrexate (30
      mg/m2), and vincristine (1 mg/m2, MIMO) given intravenously every 21 days. None
      of the patients had received prior chemotherapy for metastatic disease, although
      24 had been previously given adjuvant chemotherapy. Forty-seven patients were
      analyzed for response and toxicity. Objective response was observed in 20 of them
      (42%) with 3 complete responses (6%) stable disease in 7 (15%), and progression
      in 19 (40%). Best responses were achieved in lung metastases. Liver metastases
      did not respond. The median duration of response was 9 months and the median time
      to disease progression 11 months. Toxicity was mild. Nausea and myelotoxicity
      were the main side effects. MIMO was found to be an effective and well tolerated
      first-line treatment for advanced breast cancer. The regimen was compared
      historically with MIMO plus carboplatin. The two types of treatment were found
      equipotent, with MIMO being less toxic.

PMID- 9260596
TI  - Dose intensity phase I/II trial with carboplatin, ifosfamide, etoposide and
      vincristine combined with filgrastim in patients with small-cell lung cancer.
AB  - BACKGROUND: The purpose of the study was to evaluate the feasibility of
      increasing dose intensity by a stepwise reduction of the time intervals between
      chemotherapy cycles in separate patient cohorts with small-cell lung cancer.
      Patients received up to 6 courses of combination chemotherapy with carboplatin,
      etoposide, ifosfamide and vincristine followed by support with filgrastim. Dose
      intensity, incidence, duration and severity of neutropenic fever and infections,
      objective response to chemotherapy, and safety of filgrastim were determined.
      PATIENTS AND METHODS: 29 patients with small-cell lung cancer (limited disease:
      2, extensive disease: 27) were treated with a combination of carboplatin 250
      mg/m2 i.v. day 1, ifosfamide 2 g/m2 and etoposide 120 mg/m2 i.v. days 1 and 2,
      etoposide 120 mg/m2 orally day 3, and vincristine 1.4 mg/m2 day 14. Initially,
      filgrastim (5 micrograms/kg) was administered subcutaneously from day 7 to 16.
      With shorter treatment intervals, filgrastim was administered on days 4-16 or 4
      14. RESULTS: An overall increase in dose intensity by a factor of 1.44 was
      achieved after reducing the treatment interval from 27 to 17 days. Further
      reduction to 14 days was not feasible due to persistent thrombocytopenia. Six
      patients (21%) developed a total of 9 febrile episodes, and 14 patients (48%) had
      to be withdrawn from the study before the completion of six cycles of
      chemotherapy. The median duration of infectious episodes was 6 days. Overall, a
      total of 22 of 27 evaluable patients had an objective response. Longer treatment
      intervals resulted in a lower probability for objective response (> or = 23 days:
      10/14 patients vs. < or = 17 days: 7/7 patients). CONCLUSION: Filgrastim allows
      for the reduction of treatment intervals in patients with small-cell lung cancer
      and increased dose intensity with acceptable hematologic and nonhematologic
      toxicities.

PMID- 9260598
TI  - Results of the cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) +/
      bleomycin treatment and evaluation of prognostic factors in aggressive lymphomas
      in Turkey.
AB  - Prognostic factors and the results of the cyclophosphamide, doxorubicin,
      vincristine, prednisolone (CHOP) +/- bleomycin treatment in 93 consecutive
      evaluable patients with aggressive lymphomas are presented. The overall response
      rate, excluding 7 patients with primary extranodal lymphoma who were in complete
      remission after surgery, was 83% with a complete response (CR) rate of 69%.
      Overall survival (OS) rates of all patients and disease-free survival (DFS) rates
      of complete responders at 4 years were 52 and 66%, respectively. Almost two
      thirds of the patients could be given at least 75% of the planned chemotherapy
      doses. Treatment toxicities were in acceptable limits, only 10% of the patients
      had grade 3-4 hematological toxicity. Age, performance status (PS), stage, number
      of extranodal sites (ENS) (< or = 1 vs. > 1), B symptoms, serum LDH levels were
      evaluated as prognostic factors. Univariate survival analysis yielded stage, ENS
      and PS as significant prognostic factors for OS (p = 0.0009, p = 0.0028 and p =
      0.0155, respectively). Only involvement of more than 1 ENS was strongly
      associated with low CR (p = 0.0479) and high relapse rates (p = 0.0118), and it
      was also determined as the only independent prognostic factor for OS in patients
      younger than 60 (p = 0.0015). A modified age-adjusted prognostic index, including
      ENS in addition to stage, LDH and PS, was found to be more significant than the
      original age-adjusted International Prognostic Index (IPI) for both DFS (p =
      0.0030) and OS (p < 0.00001). In conclusion, modified age-adjusted index may be a
      convenient alternative to the original age-adjusted IPI to identify high-risk
      patients with aggressive lymphomas in Turkey and probably also in other
      developing countries for experimental intensive regimens.

PMID- 9260600
TI  - Detection of early ototoxic effect in testicular-cancer patients treated with
      cisplatin by transiently evoked otoacoustic emission: a pilot study.
AB  - The outlook for patients with testicular germ cell cancer was dramatically
      improved by the introduction of cisplatin. Well-known side effects of cisplatin
      (nausea, vomiting, nephrotoxicity, myelosuppression) can be managed with
      preventive methods. The long life expectancy after this therapy draws attention
      to long-term side effects. The ototoxic side effects were scarcely studied,
      although nowadays, they can be a dose-limiting side effect of cisplatin. PATIENTS
      AND METHODS: As the literature shows, the ototoxic side effects of cisplatin have
      been studied mostly by conventional methods. The authors used transiently evoked
      otoacoustic emissions to determine whether the administration of 20 mg/m2 body
      surface cisplatin daily (in combination with other antitumor drugs) for 5 days
      alters the amplitude of the transient otoacoustic emission. RESULTS: The results
      did not show any significant amplitude change after 20 mg/m2 cisplatin daily for
      5 days, in contrast with other studies that described a broad frequency reduction
      of the emission amplitude in 30-86% of cases treated with 100 mg/m2 of cisplatin
      for 1 day. CONCLUSION: The authors suggest that between similarly effective
      regimens, those containing lower daily cisplatin doses should be used.

PMID- 9260599
TI  - Ondansetron suppository: a randomised, double-blind, double-dummy, parallel-group
      comparison with oral ondansetron for the prevention of cyclophosphamide-induced
      emesis and nausea. The Ondansetron Suppository emesis study group.
AB  - This multinational, multicentre, randomised, parallel-group study compared the
      safety, tolerability and efficacy of ondansetron 8 mg orally twice a day with
      ondansetron suppository 16 mg once daily in patients receiving cyclophosphamide
      containing chemotherapy. A total of 406 patients were randomised to receive
      ondansetron 8 mg p.o. (198 patients) or ondansetron suppository (208 patients)
      medication in a double-blind, double-dummy trial. The primary efficacy analysis
      revealed that ondansetron provided good anti-emetic control with 81% of patients
      in the 8 mg p.o. b.d. group and 73% of patients in the 16 mg ondansetron
      suppository o.d. group experiencing complete or major control of emesis (< or = 2
      emetic episodes) on the worst day of days 1-3. The 90% confidence interval for
      the difference between the two treatments for complete or major control (1.4,
      15.0%) showed that the treatments could be regarded as equivalent. A difference
      in favour of oral ondansetron treatment was noted for the complete control (0
      emetic episodes) rates over days 1-3, but no differences were found on day 1.
      There were no significant differences in the distribution of nausea grades
      between the treatment groups on the worst day of days 1-3 or on day 1. The
      incidence of adverse events was similar for the two treatment groups, the most
      frequently reported events were headache and constipation. There were no
      significant laboratory findings in either treatment group. In conclusion this
      study showed that the ondansetron treatments could be regarded as equivalent for
      the primary efficacy endpoint and that ondansetron suppository was well tolerated
      and effective in the prevention of cyclophosphamide-induced emesis.

PMID- 9260601
TI  - Prognostic significance of the expressions of metallothionein, glutathione-S
      transferase-pi, and P-glycoprotein in curatively resected gastric cancer.
AB  - Although experimental studies indicate that overexpression of metallothionein
      (MT), glutathione-S-transferase-pi (GST-pi), or P-glycoprotein (P-GP) is related
      to the drug resistance of cancer cells, the clinical significance of the
      overexpression remains to be elucidated. The expressions of MT, GST-pi, and P-GP
      wre evaluated immunohistochemically in 74 specimens of gastric adenocarcinoma in
      T1-3N1-2 stages which were resected with curative intent. Fluorinated
      pyrimidines, mitomycin C, and Adriamycin were prescribed in 73, 54, and 2
      patients, respectively. The staining characteristics were investigated in
      relation to the clinical results. The cell-proliferative activity was studied
      with anti-proliferating cell nuclear antigen antibody. Expressions of GST-pi and
      P-GP correlated with the staining intensity of normal mucosa. Five-year disease
      free survival rates (DFSRs) of GST-pi-negative and GST-pi-positive groups were
      75.0 and 49.0%. The 5-year DFSRs of P-GP-negative and P-GP-positive groups were
      68.2 and 38.6%. Concurrent expression among the three proteins was associated
      with the survival: 5-year DFSR of no- or one-protein-positive group was 75.0%,
      while those of 2- and 3-protein-positive groups were 56.0 and 38.9%,
      respectively. Tumors concurrently expressing 2 or 3 proteins have a high
      proliferative activity. Expressions of MT, GST-pi, and P-GP by the tumor are
      associated with a poorer prognosis of the patients.

PMID- 9260602
TI  - Serum-soluble IL-2 receptor and IL-6 levels in patients with melanoma.
AB  - Elevated soluble IL-2 receptor (sIL-2R) and IL-6 serum concentrations have been
      reported as adverse prognostic factors in several types of cancer. In order to
      determine whether these factors are predictive of metastatic progression in
      melanoma, sIL-2R and IL-6 levels were measured in sera from 172 patients with
      melanoma and 60 in healthy controls. Mean sIL-2R values were significantly higher
      in the patients than in normal controls and the highest values were observed in
      those that developed metastasis during follow-up. However, no correlation was
      found with the stage of the disease. Serum IL-6 levels were found to be
      correlated with age and sex, but not correlated with sIL-2R levels. Statistical
      analysis was based on logistic and Cox regression models. The factors considered
      were age, sex, stage, disease-free interval and serum sIL-2R and IL-6 levels. The
      analysis showed that only the sIL-2R value is significantly linked to metastatic
      progression. This finding suggests that high serum levels of sIL-2R could be a
      predictive factor of metastatic progression in malignant melanoma.

PMID- 9260603
TI  - Immunohistochemical detection of proliferating cell nuclear antigen and p53
      expression in carcinoma of the extrahepatic bile duct.
AB  - We used an immunohistochemical method to determine the concentrations of p53 and
      proliferating cell nuclear antigen (PCNA) to evaluate their usefulness as a
      predictor of malignancy and examined the relationship between PCNA and p53 in
      carcinomas of the extrahepatic bile duct (EHBD). Paraffin-embedded specimens from
      46 patients were immunostained for PCNA and p53 using PC10 and DO7 monoclonal
      antibodies, respectively. The PCNA labeling index (LI) was closely associated
      with the stages of the tumor and depth of invasion (p < 0.05). The cumulative
      survival rate of patients with a low PCNA LI (LI < 47%) was found to be
      significantly better than that of patients with a high PCNA LI (LI > or = 47%) in
      all cases and patients with advanced cancer by univariate analysis (p < 0.05),
      but PCNA LI was not an independent prognostic factor in multivariate analysis. We
      detected p53 in 37% of the EHBD cancers. We also found that p53 positivity was
      not related to the percentage of PCNA-labelled cells or survival. The results
      suggest that PCNA immunoreactivity may be a useful predictor of malignancy in
      patients with EHBD carcinomas.

PMID- 9260604
TI  - Effects of OK-432 (picibanil) on the estrogen receptors of MCF-7 cells and
      potentiation of antiproliferative effects of tamoxifen in combination with OK
      432.
AB  - OK-432 (picibanil), a streptococcal preparation, has a strong biological response
      modifier (BRM) function and is expected to produce clinical improvement and
      prolongation of survival in treated cancer patients in Japan. We were interested
      in whether OK-432 augments estrogen receptor (ER) levels in breast cancer. To
      investigate the effect of the BRMs on cellular growth and the characteristics of
      ER and progesterone receptors (PgR) in the human breast cancer cell line MCF-7,
      we used OK-432, Krestin (PSK), a protein-bound polysaccharide extracted from
      Coriolus versicolor, and lentinan, a fungal branched (1...3)-beta-D-glycan. OK432
      and PSK dose dependently inhibited DNA synthesis of MCF-7 cells, and the 50%
      inhibitory concentrations of OK-432 and PSK were 1.2 KE (klinische Einheit,
      clinical unit)/ml and 200 micrograms/ml, respectively. Lentinan showed no direct
      anticancer effect in vitro. We found that OK-432 induced a 2-fold increase in ER
      levels in MCF-7 cells at 0.005 KE/ml, but not in PgR. Lentinan and low-dose PSK
      did not change ER or PgR levels, but high-dose PSK decreased ER and PgR. We also
      studied the combined effect of OK-432 and antiestrogens, tamoxifen (TAM) and DP
      TAT-59. The combined treatment with OK-432 and TAM showed an additive inhibitory
      effect on MCF-7 cells. These results suggest that OK-432 may augment the
      therapeutic effect of TAM in breast cancer.

PMID- 9260605
TI  - Effect of tamoxifen on pS2 expression in human breast cancers.
AB  - pS2 protein expression is induced by estrogen through estrogen receptors (ER),
      and is known to be inhibited by antiestrogen in the breast cancer cell line MCF
      7. The present study was undertaken to determine whether pS2 expression may be
      inhibited by the antiestrogen tamoxifen (TAM) human breast cancer. pS2 expression
      was immunohistochemically investigated in 22 patients treated preoperatively with
      TAM and in 45 without TAM treatment (control group). Immunostaining was
      considered positive when 10% of tumor cells showed cytoplasmic staining. We found
      that 94% of the pS2-positive tumors were ER-positive (ER+), and there was a
      significant association between the two proteins (p < 0.0001). In ER+ tumors, pS2
      expression was seen in only 21% (3 of 14) of the TAM+ group, compared to 70% (16
      of 23) of the control group. Statistical analysis of these data indicated a high
      likelihood (p = 0.006) of TAM treatment being associated with inhibition of pS2
      expression in human breast cancers.

PMID- 9260606
TI  - Comparison of cytogenetics, cytokine secretion, and oncogene expression in
      primary cultures of renal carcinoma cells.
AB  - We compared the cytogenetic pattern of 20 different primary tumor cell cultures
      (PTCC) of renal cell carcinoma (RCC) to their cytokine secretion and oncogene
      expression. High secretion of IL-6 (gene locus on chromosome 7p21-p14) was
      correlated with the gain of an additional chromosome 7. Structural changes
      involving chromosome 5q22, the site of the GM-CSF gene, were matched with the
      high secretion of GM-CSF in PTCC. No such association was found for beta 2
      microglobulin, TGF-beta 1, TNF-alpha, IL-8, and oncogenes, such as c-fos, c-myc,
      and pan-ras. Our approach may be useful in simultaneously analyzing several
      factors contributing to tumor progression and may contribute to understanding the
      multistep development of RCC.

PMID- 9260608
TI  - Comparative classification for fractures of the distal end of the radius.
AB  - As suggested by Muller, a useful classification system for distal radius
      fractures must consider the severity of the bone lesion and serve as a basis for
      treatment and for evaluation of outcome. Although these fractures have long been
      considered to be Colles or Smith's fractures, they have been subjected to
      extensive scrutiny in order to define fracture morphology and treatment
      considerations. This review highlights a number of contemporary classification
      systems for distal radius fractures, including the systems of Older et al., the
      Comprehensive Classification of fractures, the Melone intra-articular
      classification system, and that of Fernandez.

PMID- 9260607
TI  - A randomized phase II trial of two different schedules of mitomycin C and
      vinorelbine in pretreated breast cancer.

PMID- 9260609
TI  - Noninvasive measurement of distal radius instability.
AB  - Except for subjective clinical criteria, there is no formal definition of distal
      radius fracture instability in the literature. The purposes of this ex vivo
      biomechanical study were (1) to provide an objective mechanical definition of
      fracture instability and (2) to demonstrate a noninvasive method that allows for
      direct measurement of instability. The following 3 questions are addressed: (1)
      Can the stability of distal radius fractures be measured using computed
      tomography (CT)? (2) Are the stability measurements reproducible? (3) How does
      external fixation change stability? A CT technique is described that was used to
      measure displacement of fracture fragments and measure the compliance of ex vivo
      distal radius fractures before and after external fixation. Validation studies of
      the CT technique revealed a mean coefficient of variation of 0.38. There was a
      linear relationship between measured and known displacements for all 3 orthogonal
      planes (coefficient of determination 0.99; p < .01). There was significant
      fracture displacement with loads as small as 20 N. The slope of the load
      displacement curve (structural compliance) provided a quantitative measure of
      fracture instability. Fracture compliance decreased up to 69% after application
      of an external fixator.

PMID- 9260610
TI  - The risks of Kirschner wire placement in the distal radius: a comparison of
      techniques.
AB  - A comparison of percutaneous and limited open insertion of Kirschner wires (K
      wires) in the distal radius was conducted in an effort to determine which
      technique has the lower rate of iatrogenic injury. Eighty-eight K-wires were
      inserted in the distal radii of 44 fresh cadaveric arms: 44 at Lister's tubercle
      and 44 at the tip of the radial styloid. No incision was used for the
      percutaneous technique. The limited open technique included a 1.5-cm incision
      with blunt dissection and use of a soft tissue protector. To define the incidence
      of nerve or tendon damage secondary to pin placement, the cadaveric wrists were
      subsequently dissected under 3.5x loupe magnification. The distances from the K
      wires to the branches of the superficial radial nerve and to the first 3 extensor
      compartments were recorded. Structures pierced or displaced by a K-wire were
      considered potentially injured. Chi-square analysis demonstrated a significantly
      higher rate of potentially injured nerves and tendons in the percutaneous group.
      Thus, to reduce the risk of potential injuries, limited open incision, blunt
      dissection down to bone, and the use of a soft tissue protector for K-wire
      placement into the distal radius is recommended.

PMID- 9260611
TI  - Repair of acute ulnar collateral ligament injuries of the thumb
      metacarpophalangeal joint with an intraosseous suture anchor.
AB  - Thirty-six consecutive patients with 37 complete tears of the ulnar collateral
      ligament of the thumb metacarpophalangeal (MP) joint were treated with primary
      repair using a miniature intraosseous suture anchor. Thirty patients were
      evaluated by clinical examination or by questionnaire at an average of 11 months
      after repair. Loss of interphalangeal joint motion averaged 15 degrees on the
      involved side versus the other side, while loss of MP joint motion averaged 10
      degrees. There was no significant difference on stress testing measurements
      between repaired and nonrepaired thumbs. There were no instances of nerve injury,
      infection, device failure, or reoperation. The authors concluded that this is a
      safe and effective method for repair of complete tears of the ulnar collateral
      ligament of the thumb MP joint.

PMID- 9260612
TI  - Large volar plate avulsion fracture of the base of the middle phalanx with
      rotational displacement: a report of three cases.
AB  - Three cases of large volar plate avulsion fracture at the base of the middle
      phalanx with significant displacement are reported. In each case, the fracture
      fragment involved about 30% of the articular surface and was rotated 90 degrees.
      The proximal interphalangeal (PIP) joint showed loss of volar stability with
      hyperextension stress. This unusual variant of volar plate injury is thought to
      be caused by subluxation of the PIP joint. All patients underwent open reduction
      and internal fixation. The fracture healed in anatomic alignment without
      articular incongruity or instability in all cases.

PMID- 9260613
TI  - Intrinsic balancing in reconstruction of the tetraplegic hand.
AB  - This article reviews 183 hand reconstructions in 135 consecutive tetraplegic
      patients. Comparisons were made between 103 extrinsic reconstructions with
      intrinsic balancing procedures and 80 extrinsic reconstructions without intrinsic
      balancing procedures. Extrinsic reconstructions (tendon transfers and tenodesis
      in the forearm muscles) were augmented by intrinsic reconstructive procedures
      (tendon transfers or tenodesis to improve the intrinsic balance of the fingers)
      in patients exhibiting digital imbalance. Intrinsic procedures included primarily
      the flexor digitorum superficialis (FDS) lasso procedure or the intrinsic
      tenodesis procedure. The patients were stratified by level of spinal cord injury
      and by type of extrinsic and intrinsic reconstruction. Hands reconstructed with
      intrinsic balancing versus without intrinsic balancing, as well as intrinsic
      balancing using a FDS lasso procedure versus an intrinsic tenodesis procedure,
      were compared with patients with the same level of spinal cord function. Patients
      who underwent reconstructions with intrinsic balancing had more grip strength, by
      an average of 13-26 N, than those who did not undergo intrinsic balancing. When
      different intrinsic procedures were compared, there was improvement in grip
      strength and function in activities of daily living for all hands, but there was
      no significant difference between FDS lasso or intrinsic tenodesis procedures.
      The indications for intrinsic balancing during extrinsic reconstruction are
      developed into treatment algorithms based on the senior author's surgical
      experience. The authors recommended that digital intrinsic procedures be included
      in hand reconstruction for tetraplegic patients exhibiting intrinsic imbalance to
      help improve digital function and provide increased grip strength.

PMID- 9260614
TI  - Quality of life and functional outcome following brachial plexus injury.
AB  - Thirty-two patients (3 women, 29 men) participated in a mailed questionnaire
      survey to evaluate long-term subjective, employment, and functional outcome
      following surgical treatment for brachial plexus injury. The mean age was 37
      years and mean postinjury time was 7 years. The main outcome measures were
      overall life satisfaction, employment status, and the impact of the brachial
      plexus injury on life domains. Quality-of-life questions were adapted from the
      interviewer form of the U.S. General Social Survey. Considering overall life
      satisfaction, 25 patients (78%) reported at least moderate satisfaction and no
      patients reported extreme dissatisfaction. Ten patients reported that their
      injury did affect to a great deal their overall quality of life and slightly more
      than half the patients were employed at the time of the study. These outcomes
      were not affected by such patient factors as coverage by workers' compensation,
      litigation, pain, marital status, number of children, educational status, and the
      degree of functional recovery. These patient factors also did not alter the
      impact of the injury on overall life satisfaction. In spite of the devastating
      nature of these injuries, this patient population for the most part reported good
      quality of life with employment status predicted within the first year following
      injury.

PMID- 9260616
TI  - Displacement and strain of the median nerve at the wrist.
AB  - Median nerve displacement and strain in the carpal tunnel region were measured as
      functions of wrist position and carpal tunnel pressure in 5 cadaver forearms
      during simulated active finger flexion. The positions of spherical stainless
      steel markers embedded within the median nerve and flexor digitorum superficialis
      of the long finger were measured in 3 dimensions by a radiographic direct linear
      transformation technique. Each limb was tested in 3 wrist positions (60 degrees
      extension, neutral, and 60 degrees flexion) and 4 carpal tunnel pressures (0, 30,
      60, and 90 mmHg). Carpal tunnel pressure was controlled with a balloon
      angiocatheter inserted deep to the flexor digitorum profundus. The ratio of
      median nerve to flexor tendon excursion was linear and was affected by wrist
      position but not carpal tunnel pressure. Patterns of strain in the median nerve
      proximal to the flexor retinaculum were different from those of strain within the
      carpal tunnel. Nerve strains were affected by wrist position, but carpal tunnel
      pressure had no effect. The hydrostatic pressure effect associated with carpal
      tunnel syndrome does not appear to influence median nerve kinetics or kinematics
      for the wrist positions studied.

PMID- 9260615
TI  - Patients' preferences and their relationship with satisfaction following carpal
      tunnel release.
AB  - Patients' preferences for specific health outcomes in carpal tunnel syndrome
      (CTS) and their association with demographic factors and satisfaction with the
      results of surgery after 6 months were evaluated. Two hundred fifty subjects with
      CTS and enrolled in a prospective community-based cohort study in Maine completed
      a preference questionnaire before surgery. Patients were asked to specify the
      single most important reason they decided to undergo surgery and to rate the
      importance of improvement in 10 areas, including lessening of specific symptoms
      and improvement in specific functional states related to CTS. The single most
      important reason for CTS patients to have surgery was relief of night pain (37%),
      followed by relief of numbness (21%) and relief of daytime pain (13%). When
      patients were asked to rate the importance of obtaining relief from specific
      symptoms and improvement in specific functional states, relief of numbness
      received the highest rating, with 94% of the patients answering that it was
      extremely or very important. Workers' compensation recipients, patients with less
      than a college level of education, and patients with more severe symptoms and
      functional impairment at baseline assigned higher importance to symptom relief
      and functional improvement. Controlling for other predictors, higher preference
      for improved strength was associated with lower satisfaction with the results of
      the surgery at 6 months. Most CTS patients undergoing surgery have realistic
      preferences for health outcomes that are influenced by demographic and clinical
      characteristics; however, physicians should pay attention to unrealistic
      preferences that might influence patients' satisfaction with surgical results.

PMID- 9260617
TI  - The effects of tendon load and posture on carpal tunnel pressure.
AB  - Two pressure measurement techniques (catheter and bulb) were used to decompose
      the effects of tendon loads on carpal tunnel pressure (CTP). The catheter
      technique measures true hydrostatic pressure, whereas the bulb technique is a
      estimate of contact force or pressure on the median nerve. Eight cadaveric wrists
      were moved through a range of flexion-extension (0 degrees, 10 degrees, 20
      degrees, 30 degrees, and 45 degrees of each) and radioulnar deviation (10 degrees
      and 20 degrees radial and 0 degrees, 10 degrees, 20 degrees, and 30 degrees
      ulnar) while CTPs were measured under 4 muscle loading conditions with the thumb,
      index, and long finger in a pinch-grip posture. The first of these was zero load.
      Then a 1-kg mass was applied in turn to both flexors of the index and long
      fingers, the palmaris longus (PL); and the flexor pollicis longus. The
      hydrostatic pressure was found to be affected by both wrist posture and tendon
      load. With no load, highest pressures were seen in wrist extension. Muscular
      loading elevated CPT, particularly the loading of palmaris longus with the wrist
      in extension and the digital flexors with the wrist flexed. Bulb pressure
      measurements, related to local contact forces by the digital flexors, indicated
      the highest loads on the median nerve with the wrist flexed. Palmaris longus
      loading created the highest pressures in extension and only moderate pressure in
      flexion, indicating that it may alter the geometry of the transverse carpal
      ligament. In view of the data from this study, it is necessary to incorporate
      measures of hydrostatic pressure and local contact forces to describe possible
      trauma to the median nerve in the carpal tunnel, as neither appears sufficient
      when used independently.

PMID- 9260618
TI  - Assessment of the ratio of carpal contents to carpal tunnel volume in patients
      with carpal tunnel syndrome: a preliminary report.
AB  - An anatomic basis for carpal tunnel syndrome (CTS) has been proposed but not
      confirmed; both volumetric and area studies have been used to address this issue.
      The authors have demonstrated that the ratio of the carpal tunnel contents (CTC)
      to carpal tunnel volume (CTV) provides information regarding the relative free
      space in the carpal tunnel as compared with canal volume alone. This study was
      undertaken to determine whether the CTC/CTV ratio was higher for patients with
      CTS than for normal subjects. Seven asymptomatic volunteers and 7 patients with
      symptoms of CTS underwent magnetic resonance imaging (MRI) so that the CTC/CTV
      ratios could be determined. Standard radiographs were analyzed to identify plain
      radiographic variables that differed between patients with CTS and control
      subjects, and no differences were found. On MRIs, however, CTC/CTV ratios were
      noted to be higher for patients with CTS than for matched control subjects.

PMID- 9260619
TI  - Neurotization of the rat soleus muscle: a quantitative analysis of reinnervation.
AB  - Neurotization--reinnervation of muscle by direct nerve implantation--has been the
      subject of several reports. The underlying neurobiology, however, has not been
      adequately studied. The use of a combined silver-acetylcholinesterase stain was
      used in this study to identify reinnervated motor endplates and to quantify motor
      endplates reinnervated by the neurotization process. This study examined the
      effect of distance between nerve implantation and native motor endplate zone on
      the formation of ectopic motor endplates and on the total number of motor
      endplates reinnervated. Experiments were performed on the rat soleus muscle. The
      transected tibial nerve was implanted directly into the motor endplate zone
      (near, n = 10) or distally, far from the motor endplate zone (far, n = 10). After
      a reinnervation interval, frozen sections were processed to demonstrate both
      axons and motor endplates. In the near group, a mean of 566 motor endplates were
      reinnervated in the native motor endplate zone and a mean of only 13 in distant
      locations. In the far group, a mean of 362 motor endplates were reinnervated in
      the native zone, while a mean of 477 were reinnervated in distant locations.
      Significantly more ectopic motor endplates were generated by far implantation,
      and native motor endplates were increased by near implantation. The total number
      of motor endplates was independent of implant location. These experiments
      demonstrate that the distance between implanted nerve and the native motor
      endplate zone influences the morphology of reinnervation.

PMID- 9260621
TI  - Resistant herpes infection of the palm in a patient with acquired
      immunodeficiency syndrome: a case report.
AB  - An unusual case of nonhealing abscess that evolved into granulomatous lesions in
      the palm is presented. The recurrent lesions proved to be herpes simplex virus
      infection in a patient with previously undiagnosed acquired immunodeficiency
      syndrome.

PMID- 9260620
TI  - Osteomyelitis of the tubular bones of the hand.
AB  - The records of 700 patients with hand infections were reviewed. Forty-six (6%)
      had osteomyelitis of the metacarpals or phalangeal bones. The cause was post
      traumatic in 57%, postoperative in 15%, hematogenous in 13%, spread from
      contiguous infections in 9%, and unidentified in 6%. Twenty-two percent of the
      patients had vascular insufficiency and/or were immunocompromised. History,
      physical exam, plain x-rays, and open biopsy and culture were most helpful in
      establishing the diagnosis. Laboratory studies and bone scans were less helpful.
      Cultures were positive in 74% of patients, with a noteworthy number of mixed
      infections (35%) and gram-positive infections (35%). Gram-negative infections
      accounted for 15%, fungal infections for 12%, and mycobacterial infections for
      3%. Surgical management varied from simple curettage to more elaborate staged
      reconstructions and/or arthrodeses. Despite provision of aggressive surgical care
      and use of appropriate antibiotics, the overall amputation rate was 39% (18/46).
      A delay of more than 6 months from onset of symptoms to diagnosis and definitive
      treatment led to amputation in 6 of 7 patients (86%), 2 of whom had squamous-cell
      carcinoma. Of the 12 patients who underwent more than 3 surgical procedures, 8
      ultimately underwent amputation and 2 had marked disability.

PMID- 9260622
TI  - Isolated digital swelling as the initial presentation of juvenile rheumatoid
      arthritis.
AB  - Juvenile rheumatoid arthritis (JRA) is an inflammatory condition that affects
      children under 16 years of age. The cases of 7 patients with isolated finger
      swelling as the initial manifestation of JRA are reviewed. In these children, the
      diagnosis was significantly delayed (t-test, p < .0076) for up to 14 months
      (mean, 8 months) when compared to a mean of 3.4 months in the JRA patients with a
      typical onset. Of the patients with the initial presentation of isolated digital
      swelling, +/7 (57%) had disease that became polyarticular, whereas only 15% of
      the patients with the initial presentation of large-joint disease experienced
      progression to polyarticular disease (Fisher's exact test, p < .0307). This
      presentation of JRA should be recognized so that appropriate management can be
      instituted promptly.

PMID- 9260623
TI  - X-ray changes after expanded polytetrafluoroethylene (Gore-Tex) interpositional
      arthroplasty.
AB  - Thirty-one patients with degenerative osteoarthritis at the trapeziometacarpal
      joint underwent 34 expanded polytetrafluoroethylene interpositional
      arthroplasties. The average follow-up period for the group of patients was 41
      months (range, 15-82 months). Subjective results and objective measurements for
      the patients at the time of review were favorable. X-ray analysis, however,
      revealed a high incidence of osteolytic lesions associated with microparticulate
      degeneration consistent with reactive particulate synovitis. Owing to the
      unacceptably high rate of secondary osteolysis, the authors recommend that use of
      this material for trapeziometacarpal or pantrapezial arthroplasty be abandoned.

PMID- 9260624
TI  - The dorsal transposition flap for congenital contractures of the first web space:
      a 20-year experience.
AB  - Fifty-four dorsal transposition flaps were performed in 38 patients (46 hands)
      for severe congenital thumb web-space contractures. At an average follow-up
      interval of 6 years, complications or unsatisfactory results had occurred in 100%
      of symbrachydactyly patients and in 27% of all other patients. Postoperative
      first web-space angle was augmented an average of 59 degrees with a distal flap
      two-point discrimination of 8 mm. Mean postoperative pinch and grip strengths
      were 58% and 72%, respectively, of the normal contralateral hand. Parental
      satisfaction with the functional results was high, and the aesthetic results were
      generally acceptable. With the exception of symbrachydactyly patients, the dorsal
      transposition flap remains an excellent reconstructive option for severe
      congenital contractures of the thumb web space.

PMID- 9260625
TI  - Duplicated thumb bifurcation at the metacarpophalangeal joint level: factors
      affecting surgical outcome.
AB  - In order that the factors causing poor surgical outcome might be clarified, 175
      duplicated thumbs bifurcating at the metacarpophalangeal joint level were
      analyzed. Cases were further divided into types A-D, based upon the details of
      the bifurcation form; that is, based on the connection of the radial digit to the
      ulnar components by either cartilage, joint, or fibrous tissue. The incidence of
      each type was 16% for type A (wide cartilaginous connection between phalanges),
      68% for type B (2 separate phalanges), 6% for type C (cartilaginous connection to
      metacarpal), and 10% for type D (fibrous connection to joint capsule).
      Triphalangeal types and the relative size of the excised digit were determined by
      the preoperative radiograph. One hundred six cases were available for evaluation
      with a minimum of 3 years' follow-up. Good results were obtained in 50% of types
      A and C and in 80% of types B and D. Three phalanges in the preserve digits were
      observed in 10 cases and surgery on all but 1 resulted in a fair outcome. In
      cases where the size of the excised digit was more than 75% of the preserved
      digit, the results were fair or pool in 93%. The presence of subdivisions of
      types A and C, of 3 phalanges in the preserved digit, and of a relatively bigger
      excised digit were factors causing poor results, despite intensive reconstructive
      surgery.

PMID- 9260626
TI  - The three-square-flap method for reconstruction of minor syndactyly.
AB  - A three-square-flap procedure is described for surgical treatment of minor
      syndactyly. The average follow-up period in 58 cases (48 patients) was 2 years 4
      months. In the three-square-flap method, the interdigital space is regarded as a
      cube and flaps are designed on each surface of the cube (dorsal side,
      interdigital surface, and volar side); the flap on the dorsal side forms the
      basal surface of the new interdigital portion. This technique is most suitable
      for reconstruction of minor three-dimensional contracture syndactyly. This method
      does not require skin grafting; the design is uncomplicated and easy to
      understand, and the operative procedure is simple.

PMID- 9260627
TI  - Wrist arthrodesis for failed wrist implant arthroplasty.
AB  - Thirteen wrist arthrodeses were performed for failed wrist implant arthroplasties
      between 1984 and 1992. Twelve patients were available for review, with an average
      follow-up period of 28 months. The original arthroplasties consisted of 8
      silicone implants and 4 metal-plastic total wrist implants. The surgical method
      involved a tricortical iliac bone graft and an intramedullary Steinmann pin.
      There were 7 excellent results, 4 good results, and 1 poor result. All but 1
      patient had markedly improved function with no or mild pain. Seven patients had
      solid fusions and 5 patients had pseudarthroses. Four pseudarthroses occurred at
      the graft-metacarpal junction and 1 occurred at the graft-radius junction. Each
      patient with a solid fusion had an excellent result. All graft-metacarpal
      pseudarthroses were painless and did not limit the patients' activities. There
      were 17 complications in 9 patients. Wrist arthrodesis can be a successful
      salvage procedure for failed wrist implant arthroplasty in patients with
      rheumatoid arthritis. However, the complication rate can be high. Owing to the
      high incidence of distal graft-metacarpal pseudarthrosis, we recommend using more
      rigid fixation techniques in patients with failed wrist arthroplasties.

PMID- 9260628
TI  - Ulna-shortening osteotomy after failed arthroscopic debridement of the triangular
      fibrocartilage complex.
AB  - Over a 4-year period, 160 wrist arthroscopies were performed at 1 institution.
      Ninety-seven patients had central or nondetached ulnar peripheral tears of the
      triangular fibrocartilage complex (TFCC). All these patients underwent
      debridement with an arthroscopic shaver. Thirteen of the 97 had persistent pain
      in the TFCC region for more than 3 months after surgery. At an average of 8
      months after failed arthroscopic debridement of the TFCC, all 13 patients
      underwent a 2-mm-long ulna-shortening osteotomy with fixation by a 3.5-mm 6-hole
      dynamic compression plate. At follow-up examination (an average of 2.3 years
      later), 12 of the 13 had complete relief of pain at the ulnar side of the wrist.
      One patient continued to complain of pain with moderate to heavy activity use of
      her hand. Four of the 13 had postoperative complications: 1 had traumatic pull
      out of the screws requiring reinsertion and distal radius bone graft, 1 had
      nonunion at 4 months after surgery that required iliac crest bone graft, and 2
      had pain necessitation hardware removal. All 4 of these patients had no further
      problems at final follow-up evaluation. There was no statistically significant
      difference between the arthroscopic debridement alone cohort and the
      arthroscopy/ulna-shortening subgroup relative to ulnar variance or incidence of
      associated lunotriquetral ligament tears. On the basis of these findings the
      authors recommend a 2-mm-long ulna-shortening osteotomy for patients whose
      previous arthroscopic debridement for central or nondetached peripheral TFCC was
      unsuccessful in eliminating ulnar-sided wrist pain.

PMID- 9260629
TI  - Ulnar styloid impaction syndrome.
AB  - A series of 8 patients each with an excessively long ulnar styloid that was
      impacting the triquetrum, causing chondromalacia, synovitis, and pain, is
      presented. Four patients developed symptoms as a result of an injury and 4 had no
      definable acute precipitating injury. The average age at the time of surgery was
      34 years. There were 3 male and 5 female patients. The average follow-up period
      was 34 months. All patients were treated by open partial ulnar styloidectomy.
      Outcome was evaluated clinically and by means of patient questionnaire and
      radiographs. Pain decreased from a preoperative average score of 3.5 to a
      postoperative average score of 1.3, which equates to mild pain requiring no
      medication. All but 1 patient returned to their previous employment unrestricted.
      The average preoperative ulnar styloid length was 7.4 mm and the average ulnar
      styloid process index was 0.41, which is almost twice normal. There were no
      complications. It is likely that an excessively long ulnar styloid has important
      implications for the kinematics of the lunatotriquetral interval. Details of the
      diagnosis of this condition, including a new provocative test, and operative
      management are discussed.

PMID- 9260630
TI  - Closed rupture of a finger extensor following the Sauve-Kapandji procedure: a
      case report.
AB  - A case of closed rupture of the ring extensor digitorum tendon following
      performance of the Sauve-Kapandji procedure is presented. This complication is
      not rare following performance of the Darrach procedure. The operative findings
      indicated that the rupture was caused by an impingement of the tendon between the
      proximal stump of the ulna and the extensor retinaculum. The patient was
      successfully treated with shortening of the proximal ulnar stump and tendon
      transfer.

PMID- 9260631
TI  - The relative contribution of selected carpal bones to global wrist motion during
      simulated planar and out-of-plane wrist motion.
AB  - The relative contribution of the scaphoid, lunate, triquetrum, and capitate to
      wrist motion was examined in 6 fresh cadaver forearms. A wrist-joint motion
      simulator was used to dynamically move each wrist through planar and nonplanar
      motions. During wrist flexion-extension, the motion of the capitate closely
      followed the motion of the third metacarpal, while the lunate motion was
      approximately 50% of the total motion; the triquetrum, 65%, and the scaphoid,
      90%. Similar differences in motion for these carpal bones occurred during
      radioulnar deviation and circumduction and dart-throw motions. This suggests that
      the scaphoid, lunate, and triquetrum do not normally function as a single unit,
      but that each bone has an unique arc of motion during global wrist motion.

PMID- 9260632
TI  - Scapholunate dissociation: an experimental kinematic study of two types of
      indirect soft tissue repairs.
AB  - Indirect soft tissue repairs of scapholunate dissociation (SLD) address the
      pathophysiology but have been criticized for significantly limiting wrist flexion
      and altering wrist kinematics. This study was designed to analyze and compare the
      kinematics of a normal cadaveric wrist to those of 2 types of soft tissue repairs
      performed for SLD. Ten uninjured fresh cadaver arms were evaluated by
      cineradiography and standard x-rays. The average scapholunate (SL) gap was 0.9
      mm, with a SL angle of 50 degrees. A model of SLD was produced by sectioning the
      SL ligaments resulting in an average SL gap of 3.9 mm and SL angle of 66 degrees.
      The wrists were randomized to a dorsal capsulodesis repair and a distally based
      split extensor carpi radialis longus (ECRL) repair. The average SL gap after
      repair was 1.0 mm and the average SL angle was 47 degrees. The split ECRL repair
      and dorsal capsulodesis reduced scaphoid flexion with only a 10 degree and 18
      degree decrease in wrist flexion, respectively. Both repairs reduced the SLD and
      restored normal wrist kinematics.

PMID- 9260633
TI  - Scapholunate interosseous ligament sectioning adversely affects excursions of
      radial wrist extensor and flexor tendons.
AB  - Excursions of tendons around the scaphoid were measured in 6 fresh cadaver
      forearms to evaluate the role of the scapholunate interosseous ligament (SLIL) in
      wrist joint motion. Excursions of the extensor carpi radialis longus (ECRL) and
      brevis (ECRB) tendons and the flexor carpi radialis (FCR) tendon were
      continuously recorded during wrist flexion, extension, and radial and ulnar
      deviation. Tendon excursions were measured in the intact wrists and after
      complete sectioning of the SLIL. Tendon excursions were altered significantly in
      the major ranges of wrist motion after SLIL sectioning. After ligament
      sectioning, excursions of the ECRL and ECRB tendons increased significantly in
      wrist flexion and extension. Excursions of the FCR tendon increased significantly
      during wrist extension and ulnar deviation. These findings support the concepts
      that integrity of the SLIL plays an important role in wrist function and that
      injury of the ligament may cause clinical problems.

PMID- 9260634
TI  - The use of selective lymphadenectomy in squamous cell carcinoma of the wrist: a
      case report.
AB  - Squamous cell carcinoma is the second most common skin cancer in humans and has a
      rate of metastasis of 0.5%-5.9%. Regional lymphadenectomy is generally not
      recommended for patients with advanced lesions and clinically node-negative
      disease. Selective lymphadenectomy using preoperative lymphoscintigraphy and
      intraoperative radiolymphoscintigraphy and vital dye injections to identify the
      sentinel lymph node may help in staging patients with upper-extremity squamous
      cell carcinoma while avoiding the complications of a complete axillary node
      dissection. The case of a patient with a large squamous cell carcinoma of the
      wrist with clinically negative findings on axillary examination who was found to
      have a sentinel lymph node containing metastatic tumor is presented. Although
      this treatment method is still considered investigational, it holds great promise
      for nodal staging by being able to detect occult metastatic nodal disease in
      otherwise clinically node-negative patients.

PMID- 9260635
TI  - Aggressive giant cell reparative granuloma of the metacarpal: a case report.
AB  - A 67-year-old woman presented with pain and swelling over her ring metacarpal.
      There was no history of antecedent blunt or penetrating injury. X-rays showed a
      progressively destructive lesion of the metacarpal shaft and base. Subsequent
      biopsy revealed a giant cell reparative granuloma. Because of here age and the
      presence of osteoarthritis and digital stiffness, a ray amputation was carried
      out. Follow-up examination 3 years later revealed no evidence of recurrence.

PMID- 9260636
TI  - Eccrine carcinoma of the hand: a case report.

PMID- 9260637
TI  - Fibrous hamartoma of infancy in the hand: a case report.
AB  - Fibrous hamartoma of infancy (FHI) is a rare, benign tumor. The proximal upper
      extremity is most commonly involved. A previously unreported case of FHI in the
      hand is presented.

PMID- 9260638
TI  - Congenital primitive neuroectodermal tumor of the hand: a case report.
AB  - A congenital peripheral primitive neuroectodermal tumor of the hand demonstrating
      aggressive behavior by rapid growth and ulceration, as well as early diffuse
      metastasis is presented. Management consisted of below-elbow amputation and
      chemotherapy. Despite the tumor's initial response, intracranial metastases
      occurred 7 months later. The patient died shortly thereafter, 15 months after
      presentation.

PMID- 9260639
TI  - Effect of water temperature on skin wrinkling.
AB  - Determining the status of peripheral innervation can be difficult in certain
      patients. The phenomenon of skin wrinkling has been shown to be a reliable
      indicator of gross nerve function. This study examines the effect of various
      water temperatures on the time to skin wrinkling. The optimal temperature for
      testing hands is 40 degrees C and skin wrinkling should occur in approximately
      3.5 minutes.

PMID- 9260640
TI  - Treatment of thrombosed thumb artery aneurysm: a report of four cases.
AB  - Acute thrombosis of a thumb ulnar digital artery aneurysm is painful and
      associated with varying degrees of ischemia. Treatment of 4 patients with this
      condition by resection of thrombosed aneurysm and microsurgical vein graft
      reconstruction of the involved artery is discussed. Complete relief of symptoms,
      including healing of ulcerations and reversal of cold intolerance, were achieved.
      The authors recommend resection of the thrombosed thumb ulnar digital artery
      aneurysm and re-establishment of arterial flow by an interpositional vein graft.

PMID- 9260641
TI  - Nerve and tendon approximator.
AB  - A practical and simple approximating device, made from a plastic syringe and 2
      needles, is described. It allows a safe, tension-free approximation of severed
      ends of nerves or tendons.

PMID- 9260642
TI  - Arthrogryposis multiplex congenita.

PMID- 9260643
TI  - Arthrogryposis multiplex congenita: etiology, genetics, classification,
      diagnostic approach, and general aspects.
AB  - Arthrogryposis is a sign associated with many specific conditions and syndromes.
      It is a term used to describe the presence of multiple joint contractures that
      are present at birth. It can be seen in isolation or in association with other
      congenital abnormalities as part of a syndrome with or without central nervous
      system involvement. The exact pathogenesis of arthrogryposis is unknown, but all
      involve fetal akinesia (decreased fetal movement) with subsequent joint
      contractures. In this article I describe the causes, genetic aspects,
      classification, and approach to diagnosis.

PMID- 9260644
TI  - Arthrogryposis multiplex congenita: perinatal and electromyographic findings,
      disability, and psychosocial outcome.
AB  - Fifty-two patients with arthrogryposis multiplex congenita were followed up for 1
      to 36 years. There were six twin pregnancies, and delivery was complicated by
      breech position in 16 cases. In 19 cases the cause was atrophy of the alpha
      motoneurons of the spinal cord, detected by electromyography. Six patients did
      not achieve walking ability. Severe disability for other reasons was noted in two
      patients who had bilateral rigid extension contractures of the elbows and in six
      patients whose spinal deformities interfered with the balance of the trunk.
      Treatment of flexion contractures of the hips and knees seemed to be important in
      case it promotes the walking ability. Spinal deformities interfering with the
      balance of the trunk should be treated operatively. Restoration of elbow flexion
      was the main goal in operative treatment of the upper extremities. The
      intelligence of the patients was slightly above normal. The psychological
      analysis revealed significant diverging features compared with average population
      in testing situation. Socially the patients seemed to cope well.

PMID- 9260645
TI  - Multiple congenital contractures.
AB  - A cross-sectional study of 28 patients with multiple congenital contractures of
      miscellaneous origin is presented. We describe the clinical, genetic, and
      neurological diagnosis and the involvement of upper and lower extremities and
      spine. All treatments that patients received so far as well as functional outcome
      were studied. We compared these factors in children with anterior horn cell
      degeneration (AHCD) or amyoplasia with those of children with contractures of
      other origin. A correct genetical diagnosis of multiple congenital contracture is
      important because children with AHCD will need more extensive treatment than
      others, and their functional outcome seems to be worse.

PMID- 9260647
TI  - Management of knee deformity in classical arthrogryposis multiplex congenita
      (amyoplasia congenita).
AB  - We describe the management of significant knee deformity in 44 knees of 22
      patients suffering from classical arthrogryposis multiplex congenita (amyoplasia
      congenita). Follow-up ranged from a minimum of 18 months to 19 years 3 months,
      with an average 7 years 8 months. Thirteen patients showed fixed flexion of the
      knees at birth and 9 showed fixed extension. All were treated initially by
      physiotherapy and splintage, which was successful in all except 1 patient in the
      extended-knee group, whereas only 7 to 26 knees responded to physiotherapy and
      splintage alone in the flexed-knee group. Walking ability in the extended-knee
      group was high; 8 of 9 were community walkers with or without walking aids and
      orthoses and only one was a therapeutic walker. By contrast, in the flexed-knee
      group, despite posterior release surgery, which sometimes had to be repeated,
      only to 6 of 13 patients were community walkers at follow-up, 2 were household
      walkers, 3 were therapeutic walkers, and 2 had stopped walking in adolescence and
      preferred to use a wheelchair full time. Long-term splintage is recommended but
      does not always prevent recurrence of deformity. Bony surgery was used only
      toward the end of growth or in one case when very severe deformity necessitated
      its use at an early age and it subsequently had to be repeated. Despite their
      severe handicap and multiple deformities, this group of children show a
      remarkable determination to walk with or without walking aids and orthoses.

PMID- 9260646
TI  - Principles of treatment of the upper extremity in arthrogryposis multiplex
      congenita type I.
AB  - The involvement of the upper limb in arthrogryposis multiplex congenita for many
      patients means a far-reaching dependency on outside help. The extension
      contracture of the elbow joint especially makes it impossible to reach the mouth
      or to perform hygienic necessities. Therefore, the rehabilitation program
      includes an improvement of passive elbow flexion by capsulotomy or of active
      flexion by triceps transfer if possible, or both. In bilateral involvement, the
      optimal solution is to have one arm in flexion for reaching the head and mouth
      passively or even actively and one arm in extension for hygienic necessities.
      From 1973 to 1993 we performed 22 releases of the elbow contracture in 16
      children. An additional triceps transfer was performed in five elbows. The
      overall results showed a marked increase of the range of motion and a functional
      improvement concerning the daily activities (in 17 children). In 5 children there
      was no gain but also no loss of functional capacities. In 3 of 5 children with an
      additional triceps transfer, an improvement of active flexion was attained. Pre-
      and postoperative physiotherapy is at least as important as the operative
      procedure itself.

PMID- 9260648
TI  - Arthrogrypotic joint contracture at the knee and the foot: correction with a
      circular frame.
AB  - The purpose of this study was to investigate the efficacy of an external fixator
      (Ilizarov apparatus) for the treatment of severe joint contractures in patients
      with arthrogryposis multiplex congenita. Thirteen knees and 16 feet were treated
      in 13 patients at an average age of 11.9 years. The knee flexion contractures
      were corrected from 38.9 degrees preoperatively to a mean of 6.5 degrees
      postoperatively and to 17.3 degrees at follow-up (34 months). In the foot
      deformities, the equinus position was corrected from 29.7 degrees to 7.8 degrees
      on average. This external fixator is an efficient tool for correction of
      deformities in arthrogryposis.

PMID- 9260649
TI  - Closed flexible intramedullary nailing of the femoral shaft fractures in
      children.
AB  - We treated 34 femoral shaft fractures in 32 children with elastic intramedullary
      nailing using titanium rods. The 24 boys and 8 girls ranged from 6-17 years. All
      fractures united. The weight bearing was authorized at an average of 67 days and
      was complete at an average of 89 days. All children returned to school before the
      end of the second postoperative month. An an average of 2.5 years, no rotational
      malalignment was present. Neither anteroposterior nor frontal malalignment of
      more than 2 degrees was noticed. A leg length discrepancy of more than 10 mm was
      present in 3 patients (8%). No injury of femoral head vascularization or of the
      proximal or distal growth plate was noticed. In our experience, this technique
      seems to be safe for the surgical treatment of the immature femoral shaft
      fractures. The elastic properties of titanium provide a very good stability of
      the montage, when the technique is correctly performed.

PMID- 9260650
TI  - External fixation of children's fractures: use of the Orthofix Dynamic Axial
      Fixator.
AB  - We have reviewed 48 children's diaphyseal fractures of the femur and tibia
      managed with the Orthofix Dynamic Axial Fixator between 1987 and 1994. The
      indications for external fixation included open fractures, multiple injuries,
      failed conservative management, and unstable fracture configurations. All
      fractures healed without further surgical intervention, and the incidence of
      serious complications was low. Although pin track sepsis was common, compromise
      of the fixation as a result of this occurred in only one case. We conclude that
      use of the Orthofix for children's fractures is a safe and effective management
      option.

PMID- 9260651
TI  - Morphology of the acetabulum in hip dislocations caused by cerebral palsy.
AB  - Twenty-four hip joints in 20 children with spastic cerebral palsy were assessed
      by standardised three-dimensional reconstructions from computed tomographic
      scans. All the hip joints showed a channel-like ebony deformity of the acetabulum
      along which the femoral bead had slid out, indicating a unidirectional
      instability. The channel was oriented along the longitudinal axis of the body
      within a sector of 25 degrees anteroposteriorly. In relation to the pelvis, the
      dislocation was directed more dorsally by 20 degrees as a result of a flexion
      contracture of the hip. The size of the femoral head corresponded with the size
      of the acetabulum in every case, even in long-standing dislocations.

PMID- 9260652
TI  - Bilateral epiphysiodesis around the knee as treatment for excessive height in
      boys.
AB  - Between 1987 and 1993, six boys who had been predicted to grown to an excessive
      height were treated with bilateral Phemister epiphysiodesis around the knee.
      Median predicted adult height was 210.4c (range: 207.4-213.4 c), the median
      observed adult height was 201.5 c (range: 195.5-206.7 c). Median height reduction
      was 9.3 c (range: 4.1-15.3 c). Median length of follow-up was 44 months (range:
      21-84 months). At final follow-up, all patients had full range of motion, no
      infections, no pain, no angular deformities, equal leg lengths, and radiographic
      evidence of physeal closure. Bilateral Phemister epiphysiodesis around the knee
      is a good alternative to pharmacological treatment for boys with excessive
      height.

PMID- 9260653
TI  - Muscle abnormalities in idiopathic toe-walkers.
AB  - The cause of toe-walking is unknown. Muscle biopsies were taken from a group of
      25 toe-walkers who were treated at this hospital to try to identify the
      pathological cause of the condition. The most common abnormality noted was an
      increase in the proportion of type I muscle fibers with type grouping; other less
      common changes included the presence of angulated atrophic fibers and thickened
      capillaries and cases in which occasional fibers were undergoing active
      degeneration and regeneration. The combination of these changes suggests that
      there may be an underlying neuropathic process in idiopathic toe-walkers.

PMID- 9260654
TI  - Salter-Harris type III fracture-dislocation of the proximal humerus.
AB  - Salter-Harris type III fractures of the proximal humerus are rare injuries. We
      report a Salter-Harris type III anterior fracture-dislocation of the proximal
      humerus in a 10-year-old boy that was open reduced and internally stabilized. A
      bone scan performed during the initial hospitalization and at 2-year follow-up
      revealed devascularization and subsequent revascularization of the humeral head.
      At 2-year follow-up, the patient had full motion of the shoulder, no pain, and
      arm strength equal to that of the contralateral side. Four cases of Salter-Harris
      type III fractures of the proximal humerus have been previously reported; good
      early clinical outcomes were obtained in all. Despite devascularization of the
      epiphyseal fragment, excellent clinical outcomes may result.

PMID- 9260655
TI  - Bilateral congenital pseudarthrosis of the olecranon.
AB  - A case of bilateral congenital pseudarthrosis of the olecranon is reported in a
      15-month-old boy. This abnormality was noted at birth because of a fixed flexion
      deformity of both elbows. The left side was operated on at the age of 16 months
      and the right side at 21 months. Surgical exploration showed a mobile
      pseudarthrosis with a 2-cm gap between the tip of the olecranon and the nucleus,
      each one covered with cartilage. This cartilage was excised, the triceps tendon
      was lengthened to allow the lowering of the nucleus, and both fragments were
      fixed with nylon threads. The elbow was kept extended for 30 days in a plaster
      cast. Fusion was obtained shortly. At the 2-year follow-up, the function was
      nearly normal as was the radiological appearance. This abnormality is very rarely
      reported in the literature, and we emphasize the necessity of an early operation.

PMID- 9260656
TI  - Aneurysmal bone cyst in a patient with osteogenesis imperfecta.

PMID- 9260657
TI  - Analytical methods for measuring urea in pharmaceutical formulations.
AB  - Two new methods are described for the routine determination of urea that utilize
      HPTLC-densitometry and colorimetry. The methods involve derivatization of urea
      with p-dimethylaminobenzaldehyde to a yellow-coloured compound. Validation of the
      methods was accomplished with respect to linearity, accuracy, reproducibility and
      limit of detection/quantification. Both methods were compared with an enzymatic
      method previously described in the literature and were found to be in close
      agreement. The proposed methods have the advantages of being simple, rapid and
      involve a single step sample preparation. Under experimental conditions HPTLC was
      the most sensitive method.

PMID- 9260658
TI  - Propofol assay in biological fluids in pregnant women.
AB  - A rapid, accurate and sensitive UV derivative method was described for measuring
      the Propofol concentration in some biological fluids. Furthermore two alternative
      procedures, a gaschromatographic and a colorimetric, were also defined, and the
      results of the three methods, when applied on blood samples spiked with known
      amounts of analyte, were compared. The samples were preliminary purified by a
      solid phase extraction on octadecyl C18 cartridge. The UV derivative method was
      applied to a pharmacokinetic study on pregnant women undergoing cesarean
      sections. After an induction dose administration of 2.5 mg kg-1, the maternal and
      umbilical vein blood were found to have comparable concentrations of propofol,
      with a mean half like of about 3.5 min; on the contrary no detectable levels of
      the drug were found in amniotic fluid. The drug recoveries > 98% and the response
      was linear over the range 0.05-40 micrograms ml-1.

PMID- 9260659
TI  - Coulter counting and light diffraction analysis applied to characterisation of
      oil-water emulsions.
AB  - Coulter counting and light diffraction techniques were successfully applied to
      the characterisation of the droplet concentration and size distribution in
      camphene-water and cyclohexane-water emulsions. Both of these techniques required
      a dilution of the emulsion prior to analysis, and it was found that the
      destabilizing effect on the droplets of such dilution could be overcome by
      performing the analyses at temperatures below the melting point of the oil phase.
      The storage stability of the camphene-water samples at 60 degrees C was
      reasonably good with a 5-20% change in the investigated parameters over a 24 h
      period. At room temperature camphene-water samples left to stand undisturbed were
      unaffected after 24 h, while continuous mixing of the emulsion on a roller board
      brought about a rapid amalgamation of the particles into larger aggregates. This
      fusion process was fully described only with the light diffraction analysis due
      to the broader measuring range of this technique. However, analysing emulsions
      with a droplet size range covered by both techniques gave identical results.

PMID- 9260660
TI  - 750 MHz 1H NMR spectroscopy characterisation of the complex metabolic pattern of
      urine from patients with inborn errors of metabolism: 2-hydroxyglutaric aciduria
      and maple syrup urine disease.
AB  - 750 MHz 1H NMR spectroscopy has been used to characterise in detail the abnormal
      low molecular weight metabolites of urine from two patients with inborn errors of
      metabolism. One case of the rare condition 2-hydroxyglutaric aciduria has been
      examined. There is at present no rapid routine method to detect this genetic
      defect, although NMR spectroscopy of urine is shown to provide a distinctive
      pattern of resonances. Assignment of a number of prominent urinary metabolites
      not normally seen in control urine could be made on the basis of their known NMR
      spectral parameters including the diagnostic marker 2-hydroxyglutaric acid, which
      served to confirm the condition. In addition, 750 MHz 1H NMR spectroscopy has
      been used to characterise further the abnormal metabolic profile of urine from a
      patient with maple syrup urine disease. This abnormality arises from a defect in
      branched chain keto-acid decarboxylase activity and results in a build up in the
      urine of high levels of branched chain oxo- and hydroxy-acids resulting from
      altered metabolism of the branched chain amino acids, valine, leucine and
      isoleucine. A number of previously undetected abnormal metabolites have been
      identified through the use of one-dimensional and two-dimensional J-resolved and
      COSY 750 MHz 1H NMR spectroscopy, including ethanol, 2-hydroxy-isovalerate, 2,3
      dihydroxy-valerate, 2-oxo-3-methyl-n-valerate and 2-oxo-isocaproate. NMR
      spectroscopy of urine, particularly when combined with automatic data reduction
      and computer pattern recognition using a combination of biochemical markers,
      promises to provide an efficient alternative to other techniques for the
      diagnosis of inborn errors of metabolism.

PMID- 9260661
TI  - Two methods for the measurement of the dissociation pressure of a crystalline
      hydrate.
AB  - Two methods for the measurement of the characteristic dissociation pressures of a
      system containing water vapor and two different crystalline hydrates of the
      pharmaceutical compound MK-0677 are described. One method involves the
      spectroscopic determination of water in gases equilibrated with the solids at
      controlled temperatures, using an infrared spectrometer. The second method
      utilized the extrapolated onset temperature of the transition from one hydrate to
      the other at controlled humidities, as observed by differential scanning
      calorimetry. The methods give similar results for the system of interest.

PMID- 9260662
TI  - Protolytic constants of nizatidine, ranitidine and N,N'-dimethyl-2-nitro-1,1
      ethenediamine; spectrophotometric and theoretical investigation.
AB  - The prototropic exchange equilibria of two drugs, nizatidine (I) and
      ranitidine(II), and also of structurally related the N,N'-dimethyl-2-nitro-1,1
      ethenediamine molecule (III) were investigated. From the changes in electronic
      spectra in media of various acidity several protonation constants were
      determined. For pK values were -0.82, 1.95, and 6.67; for ranitidine pK values
      were 1.95 and 8.13; and for III was 2.60. The hydroxylation equilibrium constant
      in strongly alkaline media was determined too. Corresponding pK(a) values were
      13.23 for I, 13.36 for II and 13.76 for III. Molecular orbital calculations of
      electronic spectra confirmed that pK 1.95 for I and II, and pK 2.60 for III, are
      associated with C-protonation of nitroethenediamine fragment, while all pK(a)
      values correspond to the addition of HO- anion at the same double bond.

PMID- 9260663
TI  - Spectrophotometric determination of some pharmaceutical piperazine derivatives
      through charge-transfer and ion-pair complexation reactions.
AB  - Simple and sensitive spectrophotometric methods are described for the assay of
      three piperazine derivatives; ketoconazole, piribedil and prazosin hydrochloride
      based on charge-transfer and ion-pair complexation reactions. The first method is
      based on the reaction of the basic drug with 2,3-dichloro-5,6-dicyano-p
      benzoquinone (DDQ) in acetonitrile. The orange-red colour formed due to the
      formation of charge-transfer complex showed maximum absorbance at 460 nm. The
      second method is based upon the interaction of the basic drug in dry chloroform
      with bromophenol blue (BPB) in the same solvent to produce a stable yellow ion
      pair complex which absorbs at 410 nm. Beer's law was obeyed for both methods and
      the relative standard deviations were found to be less than 1%. The two methods
      can be applied to the analysis of tablets, with no evidence of interference from
      excipients. A more detailed investigation of the complex was made with respect to
      its composition, association constant and free energy change.

PMID- 9260664
TI  - Spectrophotometric methods for the determination of cephradine or ceftazidine in
      human urine using batch and flow-injection procedures.
AB  - Sensitive and fast spectrophotometric methods for the determination of cephradine
      or ceftazidine in human urine, based on the formation of compounds between these
      drugs and Pd(II), are described. In the batch procedures the calibration graphs
      resulting from the measurement of the absorbance at 330 nm is linear over the
      range 5.0-60.0 micrograms. ml-1 for cephradine and 3.0-60.0 micrograms ml-1 for
      ceftazidine. The methods were successfully adapted to FI-systems, the peak
      heights being proportional to cephalosporin concentration over the range 5.0-60.0
      micrograms ml-1 for cephradine and 3.0-60.0 micrograms ml-1 for ceftazidine. The
      sampling frequency was 60 h-1 with a sample injection of 72 microliters.

PMID- 9260665
TI  - Voltammetric determination of droperidol and benperidol.
AB  - In this study two butyrophenones, droperidol and benperidol were voltammetrically
      investigated using platinum and specially activated glass carbon electrodes. The
      behaviours of the substance were investigated in various electrolyte solutions
      having different pH values and by different scan rates. As a result of the
      studies it was shown that the quantitative determinations of the substances from
      their pharmaceutical preparations could be made rapidly and simply without any
      separation from the excipients.

PMID- 9260666
TI  - Spectrofluorometric estimation of aspirin and dipyridamole in pure admixtures and
      in dosage forms.
AB  - Aspirin and dipyridamole in pure admixtures and in dosage forms have been
      estimated by spectrofluorometry. Aspirin (2-12 mcg ml-1) was estimated in 1% v/v
      glacial acetic acid in chloroform using 246 and 345 nm for excitation and
      emission respectively. Dipyridamole (2-12 mcg ml-1) has been estimated in
      chloroform using 420 nm for excitation and 475 nm for emission. The non
      interference of the excipients as well as the drugs in the estimation of each
      other, as evidenced by the results, indicate that this method may be used for the
      routine estimation of aspirin and dipyridamole in tablet preparations.

PMID- 9260667
TI  - Metered dose inhalers III: Metaproterenol sulphate; particle size distribution
      and dose uniformity.
AB  - Three American products and one Canadian product were examined for content
      uniformity and particle size distribution. The results showed that not all
      products performed equally well. Some of the products exhibited high sprays early
      in the canister lifetime and all products demonstrated loss of prime. The
      particle size distributions were determined using the Andersen cascade impactor
      (USP Induction Port) and the fine particle fraction was determined using the twin
      impinger. The results showed that three of the four products had similar particle
      size distribution profiles. Both the Andersen cascade impactor and the twin
      impinger yielded the same trends in the amount of drug substance delivered to the
      fine particle fraction.

PMID- 9260668
TI  - A quantitative circular dichroic investigation of the binding of the enantiomers
      of ibuprofen and naproxen to human serum albumin.
AB  - The binding constants for racemic, R and S naproxen and ibuprofen to human serum
      albumin have been determined by a circular dichroic technique. The ibuprofens and
      naproxens show no measurable extrinsic optical activity on interaction with the
      protein, and so the extrinsic Cotton effect shown following the diazepam-albumin
      interaction is used as a probe. The presence of the drugs reduce the amount of
      diazepam bound as shown by the interaction is used as a probe. The presence of
      the drugs reduce the amount of diazepam bound as shown by the reduced size of the
      induced ellipticity. The calculated primary binding constants show that the S
      form of both drugs bind to the albumin more tightly than the R form and that the
      racemic forms bind less tightly than either enantiomer.

PMID- 9260669
TI  - Determination of paracetamol in pure form and in dosage forms using N,N-dibromo
      dimethylhydantoin.
AB  - Paracetamol (Acetaminophen) is one of the most frequently used analgesic drugs.
      At therapeutic dosage levels the drug is relatively non-toxic. Because of its
      increasing therapeutic use, its assay and quality control are of vital
      importance. A number of methods, including instrumental and titrimetric, are
      available for the quantitative determination of paracetamol in literature. A
      simple and accurate titrimetric method has been developed for the assay of
      paracetamol in pure form and in dosage forms, using N,N-dibromo dimethylhydantoin
      (DBH). Though a number of N-halo compounds are available for the determination of
      pharmaceuticals, DBH has greater advantages over such reagents.

PMID- 9260670
TI  - Miniaturized HPLC and ionspray mass spectrometry applied to the analysis of
      Paclitaxel and taxanes.
AB  - Analysis of the antitumor agent Paclitaxel, related taxane analogues and yew tree
      bark extracts has been carried out using an HPLC system capable of performing
      chromatographic separations with conventional, small-bore, and micro-bore
      columns. Both diode array detector and mass spectrometry were incorporated into
      this system, providing additional spectral and structural information for
      identification of unknown samples. In conjunction with some basic theoretical
      studies dealing with miniaturized HPLC systems, experiments were designed to
      minimize the contribution of extra-column variances. Three chromatographic
      columns, 4.6, 2 and 1 mm i.d., were elevated using a standard mixture consisting
      of Paclitaxel and three analogues. The experimental results obtained in these
      columns demonstrated good correlation with theoretical calculations with respect
      to the sensitivity enhancement. Studies on the combination of miniaturized HPLC
      with ionspray mass spectrometry for Paclitaxel samples showed dramatic
      improvement of MS performance as compared to conventional LC/MS. The advantages
      of this miniaturized LC/MS system are evidenced by enhanced mass sensitivity,
      which was more that two order of magnitude higher when changed from a 4.6 mm i.d.
      column to a 2.0 mm i.d. column, greatly improved peak shape, and the potential
      gain of efficiency. These studies demonstrate great potential of miniaturized
      HPLC/MS systems for structural characterization and confirmation of various
      pharmaceutical compounds.

PMID- 9260671
TI  - Solid phase extraction and HPLC determination of 9-benzyladenine and isomeric 9
      (nitrobenzyl)adenines and their metabolic N1-oxides present in microsomal
      incubates.
AB  - 9-Benzyladenine, 9-(2-nitrobenzyl)adenine, 9-(3-nitrobenzyl)adenine and 9-(4
      nitrobenzyl)adenine were metabolized to 9-benzyladenine-N1-oxide, 9-(2
      nitrobenzyl)adenine-n1-oxide, 9-(3-nitrobenzyl)adenine-N1-oxide and 9-(4
      nitrobenzyl)adenine-N1-oxide, respectively, by animal hepatic microsomes. For the
      quantitative determination of the substrates and metabolites present in
      microsomal incubates, an off-line solid phase extraction procedure, using columns
      paced with C18 silica bonded phase, was developed. The extraction recovery for
      these 9-alkyladenines and their N1-oxides was in the range of 92-101%. A reversed
      phase HPLC method was established with an ODS column at a column temperature of
      50 degrees C. The mobile phase consisted of H20-MeOH-diethylamine (65:35:0.5,
      v/v/v). pH 6.8. The above analytes were monitored at 233 nm and retention times
      of all analytes were within 6-14 min. The within-day coefficients of variation
      (CV) for the determinations were in an acceptable range. The biotransformation of
      BA and NBAs to N1-oxides by hamster microsomes was determined under the
      experimental conditions employed.

PMID- 9260672
TI  - HPCE determination of R(+) and S(-) mepivacaine in human serum using a
      derivatized cyclodextrin and ultraviolet detection.
AB  - A high performance capillary electrophoresis assay for the quantitative
      determination of R(+) and S(-) mepivacaine in human serum is reported using
      heptakis (2,6-di-O-methyl) beta-cyclodextrin as the chiral selector for the
      separation of the enantiomers. The background electrolyte was a 100 mM phosphate
      buffer (pH 2.5) containing 20 mM heptakis (2,6-di-O-methyl) beta-cyclodextrin and
      30 nM hexadecyltrimethylammonium bromide (HTAB). A 72 cm uncoated fused silica
      capillary was used for the analysis. HTAB was used as the buffer additive to
      decrease the adsorption of endogenous substances onto the silica wall. To
      separate the analytes of interest from the endogenous serum substances, a liquid
      liquid extraction procedure was used. The extraction recoveries were greater than
      70% for both R(+) and S(-) mepivacaine. The detection limits were around 150 ng
      ml-1 using 1 ml of serum and the limits of quantitation were 200 ng ml-1. The
      calibration curves were linear over a range of 200-2000 ng ml-1 with R(-)
      prilocaine as internal standard (IS) and coefficients of determination were
      greater than 0.999 (n=3). Precision and accuracy of the method were 4.1-7.2 and
      2.6-5.9%, respectively, for R(+) mepivacaine and 4.0-7.4 and 3.2-7.4% for
      respectively, for S(-) mepivacaine. The HPCE method was compared to an existing
      HPLC method in terms of sensitivity and selectivity for the routine analysis of
      the drugs.

PMID- 9260673
TI  - HPLC determination of biologically active thiols using pre-column derivatisation
      with 5,5'-dithio-(bis-2-nitrobenzoic acid).
AB  - 5,5'-Dithio-(bis-2-nitrobenzoic acid), Ellmans reagent (ESSE), is used as a pre
      column derivatisation reagent for the determination of biologically active thiols
      by HPLC. D-penicillamine, N-acetyl-d-penicillamine, N-acetylcysteine, cysteine,
      captopril and thiomalic acid all give well resolved derivatives. The calibration
      graph and reproducibility (%R.S.D. +/- 1.3%) for the analysis of glutathione
      indicates that the method could be used for quantitative analysis. ESSE is widely
      used as a reagent in thiol determinations by electronic spectroscopy via the
      detection of the Ellmans anion (ES-) generated without any prior separation
      procedures. However, there are considerable reservations over its use for the
      spectrophotometric determination of thiols because of the possibility of side
      reactions which generate another Ellmans based species (ESO2-). The assay
      described determines the thiol as a derivatised mixed disulphide (ESSR) and since
      speciation between the anion ES- and the oxidation product ESO2- occurs it
      enables the process of oxidation to be monitored simultaneously.

PMID- 9260674
TI  - Indirect enantiomeric separation of 2-arylpropionic acids and structurally
      related compounds by reversed phase HPLC.
AB  - A reversed-phase high-performance liquid chromatographic method, using an organic
      modifier-phosphate buffered mobile phase, for the determination of the
      enantiomeric composition of 2-arylpropionic acids and other structurally related
      compounds in microbial media is described. The method is based on the resolution
      of diastereoisomeric amides formed from the reaction of the arylpropionic acid
      with either (-)-(S)-alpha-methylbenzylamine or (-)-(S)-1-(naphthen-1
      yl)ethylamine in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide
      HCl and 1-hydroxybenzotriazole and incorporating an internal standard. The
      addition of sodium pentanesulphonate to the mobile phase as an ion-pairing agent
      was necessary to remove unreacted amine to avoid rapid column deterioration. The
      method provides and efficient, rapid and reproducible means of monitoring the
      microbial chiral inversion of 2-arylpropionic acids and other structurally
      related molecules.

PMID- 9260675
TI  - A modified HPLC method for monensin analysis in liposomes and nanocapsules and
      its comparison with spectrophotometric and radioactive methods.
AB  - Monensin is a carboxylic ionophore which can potentiate the immunotoxin activity
      against human tumors in vitro and in vivo. Currently monensin is being
      encapsulated in liposomes and nanocapsules in our laboratory. The reported
      methods for monensin analysis by spectrophotometric and HPLC lack the required
      sensitivity. We have developed a sensitive HPLC method for analysis on monensin.
      Separation was achieved on a Beckman C18 reverse phase column with methanol
      acetonitrile-methylene chloride-water-acetic acid (45:20:25:9.5: 0.5) as the
      mobile phase. The eluent was reacted with vanillin reagent in the post column
      reactor at 70 degrees C. The reagent reacted with monensin and formed a pink
      color, which was detected at 520 nm. The retention time of monensin was found to
      be 6 min. By using this method it was possible to quantify monensin down to 100
      ng ml-1, with a signal to noise ration of > 17:1. Linearity was observed within
      the range of 10 to 100 ng (r2 > 0.99). Inter-day standard deviations for monensin
      samples of 20, 50 and 80 ng were 0.675, 0.543 and 0.736 respectively. Alternative
      methods of analysis include using radioactive [3H]monensin in liposomes which can
      be quantified by scintillation counter. The results from the HPLC,
      spectrophotometric and radioactive method were compared and were found to be
      within acceptable limits. The HPLC method is being utilized in our laboratory for
      quantitative analysis of monensin in liposomes and nanocapsules.

PMID- 9260676
TI  - Optimisation of the reversed phase liquid chromatographic separation of
      atovaquone, proguanil and related substances.
AB  - The optimisation of the separation of the antimalarial drugs, proguanil and
      atovaquone and six related compounds was obtained by two independent optimisation
      steps; the optimisation of the mobile phase composition and the optimisation of
      the pH. This was done using window selection diagrams (WSD) and a mixture design.
      The optimal conditions allow the identification of the six related compounds down
      to 0.1%.

PMID- 9260677
TI  - Comparison of liquid and supercritical fluid chromatography for the separation of
      enantiomers on chiral stationary phases.
AB  - Comparisons of liquid (LC) and supercritical fluid chromatography (SFC) were
      conducted using commercially available chiral stationary phases (CSPs) bearing
      three different types of chiral selectors. Chiral compounds of pharmaceutical and
      agricultural interest were used to probe advantages of limitations of SFC
      relative to LC for enantiomeric separations. Column equilibrium and parameter
      optimization were generally accomplished more rapidly in SFC than in LC. Although
      improved resolution was often observed in SFC, analysis times were not always
      lower in SFC than in LC. In some instances, SFC provided separation capabilities
      not readily accessible in LC.

PMID- 9260678
TI  - Dobupride--what exactly is its degradation behavior?

PMID- 9260679
TI  - RT-PCR based diagnosis and molecular characterisation of mumps viruses derived
      from clinical specimens collected during the 1996 mumps outbreak in Portugal.
AB  - Clinical specimens collected during an outbreak of mumps were characterised by RT
      PCR, nested PCR, and nucleotide sequencing. Mumps virus was positively identified
      in 12/21(57%) saliva, 9/21(43%), throat and 1/33(3%) urine specimens and further
      sequence comparison revealed that at least six strains of viruses, which differed
      from 0-9.43% at the nucleotide levels, were cocirculating during the epidemic.
      However, phylogenetic analysis showed that these viruses grouped with two
      previously identified lineages which were mostly composed of other European mumps
      virus isolates.

PMID- 9260680
TI  - Quantification of infectious duck hepatitis B virus by radioimmunofocus assay.
AB  - A simple method is described for the precise quantification of infectious duck
      hepatitis B virus (DHBV) in cell culture, using a radioimmunofocus assay (RIFA).
      Primary duck hepatocyte cell cultures were infected with serial dilutions of
      viral samples as for a plaque assay, but then maintained with liquid overlay
      medium. After incubation for up to 14 days, cell monolayers were fixed with
      acetone, then stained with a monoclonal antibody to DHBV L protein followed by
      secondary antibody labelled with 125I. Foci of infection (representing individual
      infectious particles in the inoculum) were detected by autoradiography. The
      number of foci recovered was increased by addition of dimethyl sulphoxide to
      culture medium, but was not appreciably altered by the use of semi-solid medium.
      The titre of virus suspensions determined by RIFA correlated well with titration
      in ducklings. The RIFA is a useful method for titration of DHBV, as it has a wide
      dynamic range and is well suited to parallel titration of large numbers of
      samples. This assay will have wide use for the analysis of DHBV growth kinetics,
      antiviral efficacy, and virus inactivation procedures.

PMID- 9260682
TI  - High rate of hepatitis C virus infection in an isolated community: persistent
      hyperendemicity or period-related phenomena?
AB  - We investigated underlying risks for hyperendemic hepatitis C virus (HCV)
      infection among the 1853 inhabitants of a mountainous village in Eastern Taiwan
      with high prevalence of HCV and hepatitis B virus (HBV). Among the 80 selected
      adults, we found that having resided away from the village before 1985 was
      protective against HCV infection, while residing in the village after 1985 posed
      little risk for HCV infection to children and young adults < 30 years of age.
      Among the 559 school children 7 through 14 years of age, anti-HCV prevalence was
      1.9%, and the HBV carrier rate was 29%. Following up 270 children 1 year later,
      we found that new HCV infection occurred in 0.74% and new or repeated HBV
      infection occurred in 6.5% of the children, indicating distinct transmission
      patterns between HBV and HCV. Children of anti-HCV-positive mothers were either
      anti-HCV-negative or were infected by distinct genotypes of HCV from those
      infecting their mothers; most married couples in whom both were infected, were
      infected by HCV of discordant genotypes, indicating negligible importance of
      sexual or vertical HCV transmission. A case-control study comparing 13 anti-HCV
      positive and 53 anti-HCV-negative children showed that having received parenteral
      medication in local clinics was a significant risk for HCV infection. Our data
      indicate that, unlike the case of HBV, HCV transmission by vertical or sexual
      route, or through casual contact are extremely inefficient, and our data further
      suggest that HCV hyperendemicity is unlikely to persist as a result of the more
      stringent practice of parenteral precautions in nearly all aspects of daily life.

PMID- 9260681
TI  - Spread of measles virus through axonal pathways into limbic structures in the
      brain of TAP1 -/- mice.
AB  - The spread of measles virus into the brain was studied exploiting the olfactory
      pathway, which represents an important route of neuroinvasion by viruses. The
      virus was injected into the main olfactory bulb of wild-type mice and mice with
      disrupted TAP1 gene (TAP refers to the Transporter associated with Antigen
      Presentation), which codes for products essential for the cell-mediated immune
      response. Virus invasion was monitored for 4 weeks by immunohistochemistry. The
      distribution of measles virus was found to be restricted to brain areas connected
      with the olfactory bulbs. However, in the wild-type mice there was a marked
      infiltration of lymphocytes in the infected brain structures, and the virus did
      not pass beyond the piriform cortex. In the TAP1 -/- mice the virus spread more
      extensively along olfactory projections into the limbic system and monoaminergic
      brainstem neurons. Infected mice of both types developed seizures, which may have
      been focally evoked from the piriform cortex. This study provides evidence that
      measles virus can spread through axonal pathways in the brain. The findings
      obtained in the gene-manipulated mice point out that a compromised immune state
      of the host may potentiate targeting of virus to the limbic system through
      olfactory projections.

PMID- 9260683
TI  - Sequence analysis of SRSV in fecal specimens from an epidemic of infantile
      gastroenteritis, October to December 1995, Japan.
AB  - From October to December in 1995, an epidemic of infantile gastroenteritis
      occurred all over Japan except in Hokkaido and Okinawa prefectures. The number of
      infected infants and young children was estimated to be over 5 million cases
      [Editorial, IASR 1996]. The stool specimens from patients were examined for the
      presence of small round structured viruses (SRSVs) by reverse transcription
      polymerase chain reaction (RT-PCR) and nucleotide sequencing of parts of the RNA
      dependent RNA polymerase region. Thirty-five of 87 stool specimens examined gave
      positive results. Genomic variation was investigated by sequence analysis of a
      327 bp cDNA region. The nucleotide and deduced amino acid sequences of the ten
      strains segregated into two distinct groups; one showed 96.0-100% nucleotide and
      99.1-100% amino acid identity, the others showed 91.4-99.7% nucleotide and 93.5
      100% identity. The main mechanism of transmission remains unknown. However, these
      data suggest the possibility of person-to-person spread by two or more kinds of
      SRSV.

PMID- 9260684
TI  - GB virus-C/hepatitis G virus infection in prostitutes: possible role of sexual
      transmission.
AB  - The modes of transmission of GB virus-C/hepatitis G virus (GBV-C/HGV) other than
      by blood transfusion are largely unknown. The prevalence of GBV-C/HGV viremia and
      the associated risk factors in 145 female prostitutes were examined. The
      seroprevalence of hepatitis B surface antigen (HBsAg), antibodies to hepatitis C
      virus (anti-HCV), and GBV-C/HGV RNA were 14%, 18%, and 11%, respectively. The
      demographic characteristics were similar between subjects with and without HBsAg.
      In contrast, those with HCV or GBV-C/HGV infection had practised longer as
      prostitutes and received blood transfusion more frequently. Moreover, the
      prevalence of GBV-C/HGV RNA and anti-HCV tended to increase in parallel with the
      duration of prostitution. These results suggest that like HCV, sexual
      transmission of GBV-C/HGV occurs and the risk increased with prolonged duration
      of exposure. The transmission efficiency between GBV-C/HGV and HCV appears to be
      similar.

PMID- 9260686
TI  - Serotyping and genotyping of hepatitis C virus (HCV) strains in chronic HCV
      infection. Commission Hepatologie du CREGG. Club de Reflexion des Cabinets de
      Groupes en GastroEnterologie.
AB  - Hepatitis C virus (HCV) genotypes can be established by methods based on PCR
      typing and serological typing. The accuracy of these methods depends on their
      sensitivity and specificity. These should be compared with the reference method,
      direct sequencing, and analysis of viral genomes. Among the serologic methods
      recently developed, the performance of a new serotyping assay (RIBA HCV 3.0 SIA,
      Chiron corporation, Emeryville) was assessed using a panel of 147 well
      characterized French isolates from chronic hepatitis C patients. Definitive
      genotypes of the isolates were established by direct sequencing in 5' NC and in
      some cases in NS-5B. HCV serotypes 1, 2, and 3 were determined by measuring type
      specific antibodies to core and NS-4 derived peptide antigens. Of the 147 sera,
      serotypic-specific antibodies were detected in 136 (sensitivity, 92.5%). The
      specificity of the RIBA SIA HCV serotyping assay was 92.6% (including samples
      with mixed results); without these, the specificity was 80.1%. Analysis of the 28
      discrepant samples showed that (1) a different serotype was found in 18 samples
      including five for genotype 1, three for genotype 2, two for genotype 3, five for
      genotype 4, and three for genotype 5, and that (2) ten patients showed a
      reactivity with mixed serotypes, one had circulating antibodies to type 1 or 2,
      and nine had circulating antibodies to type 1 or 3. In summary, except for
      genotypes 4 and 5, the results of the test were well correlated (85.7%) with
      those of direct sequence genotyping. The former test is rapid and does not
      require the strict HCV RNA storage and preservation conditions of the latter.
      This new method may thus be considered as an alternative for HCV typing. However,
      although it is convenient, its lower sensitivity compared to the molecular typing
      method and the discrepant results limit its routine use in a clinical context.

PMID- 9260685
TI  - Detection of hepatitis G virus RNA in patients with hepatitis B, hepatitis C, and
      non-A-E hepatitis by RT-PCR using multiple primer sets.
AB  - Hepatitis G virus(HGV)/GB virus C(GBV-C) is a newly identified virus associated
      with human hepatitis. The preliminary prevalence studies of HGV infection in
      Japan were entirely based on the detection of HGV RNA by RT-PCR. However, the
      selection of the different primer sets in such assay may influence sensitivity of
      the test because of the extensive genetic heterogeneity of HGV, and influence the
      estimation of the prevalence of HGV. To address this potential problem, we
      designed two primer sets from well conserved domains in the 5'NC and NS5 regions
      of HGV genome, and tested them together with the NS3-derived primer set in RT-PCR
      for their ability to detect HGV RNA in serial dilution of synthetic viral RNA
      templates. Subsequently, we used these three primer sets to detect HGV RNA in the
      sera of 371 Japanese patients with hepatitis B, hepatitis C, and non-A-E
      hepatitis. The results indicated that the primer set derived from the 5'NC region
      appeared to be most effective in detecting HGV RNA. The results also showed that
      only two out of the 126 patients (1.6%) with non-A-E hepatitis were positive for
      HGV RNA although the RNA were detected more frequently in patients with hepatitis
      B (2/38; 5.3%) and hepatitis C (17/207; 8.2%), suggesting that HGV is not a
      common causative agent for non-A-E hepatitis in Japan.

PMID- 9260687
TI  - HCV genotypes in Morocco.
AB  - To determine the hepatitis C virus (HCV) genotypes circulating in Morocco, virus
      isolates from 105 chronically infected and 19 hemodialysis patients were examined
      using the line probe assay. Genotypes 1 and 2 only were found among Moroccan
      patients. Subtypes 1b (47.6%) and 2a/2c (37.1%) were the most common, whereas
      subtype 1a (2.8%) was less common. Among the hemodialysis patients, only genotype
      1 was found with a prevalence of 68.4% for subtype 1b and 15.8% for the subtype
      1a. It was also shown that the HCV genotypes distribution varies with age in both
      studied populations. Subtype 1b was most prevalent among older patients, whereas
      subtype 2a/2c was mainly found among younger ones. Although Morocco belongs to
      the African continent, the circulating HCV strains are similar to those observed
      in some American and European countries.

PMID- 9260688
TI  - Hepatitis C virus is frequently coinfected with serum marker-negative hepatitis B
      virus: probable replication promotion of the former by the latter as demonstrated
      by in vitro cotransfection.
AB  - Patients with hepatitis C have been reported occasionally to be coinfected with
      serum marker-negative (silent) hepatitis B virus (HBV). The frequency and
      significance of such coinfection were investigated. Thirty patients with
      hepatitis C virus (HCV) infections (10 acute, 10 chronic, 10 cirrhotic) were
      selected randomly; the acute cases were without serum hepatitis B surface antigen
      (HBsAg) and anti-hepatitis B core IgM, and the chronic cases were without HBsAg.
      A nested polymerase chain reaction for the X open reading frame was used to
      amplify HBV DNA in serum, and immunoperoxidase staining was carried out on liver
      biopsy specimens. Nucleotide sequencing was carried out to characterize the
      amplified HBV DNAs. In order to clarify the possibility that the silent HBV
      mutant promotes HCV replication in the liver, the full-length HCV RNA and the
      cloned silent HBV DNA dimer were cotransfected into an established cell line, HuH
      7, and the amount of secreted HCV RNA was quantified serially. The target HBV DNA
      was amplified in 26 (86.7%) of the 30 patients. Subsequent direct nucleotide
      sequencing in 9 selected patients revealed an 8-nucleotide deletion,
      characteristic of a silent HBV mutant. Immunostaining revealed hepatitis B
      surface antigen in 15 (50.0%). Cotransfected silent HBV DNA augmented the
      secretion of HCV RNA by up to 5-fold in comparison with HCV RNA transfection
      alone. In conclusion, HCV is coinfected frequently with the silent HBV mutant and
      the latter probably promotes the replication of the former in the liver.

PMID- 9260690
TI  - Human hepatitis B virus enhancer 1 is responsive to human interleukin-6.
AB  - Serum levels of interleukin-6 (IL-6) are elevated in acute and chronic hepatitis
      B patients. The effect of IL-6 and its transcription factor of NF-IL6 (a nuclear
      factor for IL-6) on hepatitis B virus (HBV) enhancer 1 (Enh1), which controls HBV
      X expression, were investigated in HepG2 cells. Twenty ng/ml of IL-6 increased 4
      fold the enhancer activity of Enh1 according to the CAT assay. The IL-6
      stimulation was abolished by introducing a mutation either in an AP-1-related
      site or a C-stretch sequence in the Enh1 sequence, demonstrating that the cis
      elements are necessary for the IL-6 response. Co-transfection of NF-IL6
      expression plasmid similarly increased the enhancer activity of Enh1 through both
      binding sites. Further, a specific complex formation of the Enh1 was detected
      using HepG2 nuclear lysates by electromobility shift assays, and the complex
      formation was increased in the lysates of cells treated with IL-6 and NF-IL6
      transfection. In competition assays, one half of the complex formed was found to
      remain in the presence of 500-times excess competitor DNA fragment harboring NF
      IL2 binding site, suggesting indirect binding of NF-IL6 to the Enh1 sequence.
      These results indicate that IL-6 increased the enhancer activity of HBV Enh1
      through signal transduction pathways, indirectly involving NF-IL6, and may
      control HBV X expression and viral replication in HBV infected liver.

PMID- 9260689
TI  - Suppressive effects of human herpesvirus 6 on in vitro colony formation of
      hematopoietic progenitor cells.
AB  - Human herpesvirus 6 (HHV-6) has been reported to be involved in bone marrow
      failure after bone marrow transplantation (BMT). To elucidate the role of HHV-6
      in the marrow failure, we examined the comparative effect of two variants of HHV
      6 (HHV-6A and HHV-6B) and human herpesvirus 7 (HHV-7) on in vitro colony
      formation of hematopoietic progenitor cells in methylcellulose semi-solid media.
      Progenitor cells prepared from cord blood mononuclear cells (CBMNCs) were
      infected with one of these viruses at various multiplicity of infection (MOI),
      and were subjected to methylcellulose colony assay. Formation of both
      granulocyte/macrophage (CFU-GM) and erythroid (BFU-E) colonies was MOI
      dependently suppressed after infection with the Z29 strain of HHV-6B. Although
      HHV-6A suppressed the formation of BFU-E colonies as efficiently as HHV-6B, the
      former did not exhibit significant suppressive effect on the formation of CFU-GM
      colonies at an MOI 1. HHV-7 had no effect on hematopoietic colony formation at
      all. Based on frequent positivity of viral DNA in single colonies obtained from
      HHV-6-infected progenitor cells by polymerase chain reaction and in situ
      hybridization, direct effects of HHV-6 on the hematopoietic progenitor cells are
      suggested as the cause of the suppression rather than indirect effects via
      accessory cells of the bone marrow.

PMID- 9260691
TI  - Phylogenetic analysis of the Caliciviruses.
AB  - A phylogenetic portrait of the genus Calicivirus in the family Caliciviridae was
      developed based upon published sequences and newly characterized calicivirus (CV)
      strains, including additional Sapporo-like HuCV strains in pediatric diarrhea
      stool specimens from South Africa, the United Kingdom, and the United States.
      Distance and parsimony methods were applied to nucleotide and amino acid
      sequences of human and animal calicivirus 3D RNA-dependent RNA polymerase
      (approximately 470nt) and capsid hypervariable regions (approximately 1,200nt) to
      generate phylogenetic trees. Pairwise amino acid identity in the 3D region among
      the Sapporo-like strains ranged from 61% to 100%. Human and animal caliciviruses
      (HuCVs and AnCVs) separated into five genogroups: small round-structured viruses
      (SRSV), Sapporo-like, and hepatitis E virus (HEV)-like HuCVs and rabbit-, and
      vesicular exanthema of swine virus (VESV)-like AnCVs, each with a distinct genome
      organization. Each genogroup, including the Sapporo-like HuCVs, subdivided
      further into subgenogroups. The capsid region trees had higher levels of
      confidence than the 3D region trees and limited conclusions about genogroups
      could be drawn from the 3D region analyses. This analysis suggested that CVs
      include five potential virus subfamilies.

PMID- 9260692
TI  - Mixed genogroup SRSV infections among a party of canoeists exposed to
      contaminated recreational water.
AB  - Samples of faeces collected from a party of canoeists involved in a
      gastroenteritis outbreak were examined by electron microscopy and RT-PCR for
      evidence of infection with SRSVs. A broadly reactive primer pair was used to
      detect SRSVs followed by application of genogroup-specific primers to SRSV
      positive specimens. Exposure data were collected by means of a questionnaire.
      SRSVs were detected in 1/4 specimens examined by EM and 3/4 by RT-PCR.
      Genogrouping, and sequencing of PCR products revealed two distinct strains: a
      genogroup I strain, related to the Desert Shield virus, and a genogroup II
      strain, related to the Lordsdale virus to be associated with the outbreak.
      Exposure data indicated that capsising and eating food before getting changed
      were associated with an increased risk of gastroenteritis and was consistent with
      infection following the consumption of contaminated water. This study confirms
      the greater sensitivity of RT-PCR for the diagnosis of SRSV infections and its
      utility, when incorporating genogroup-specific primers, in establishing more
      complex epidemiological data.

PMID- 9260693
TI  - Prevalence of antibodies to hepatitis A, C, and E viruses in different ethnic
      groups in French Guiana.
AB  - In order to determine the prevalence of antibodies to hepatitis A, C, and E
      viruses (HAV, HCV, and HEV) in the various ethnic groups and areas of French
      Guiana, sera (996 for HCV and HEV, 941 for HAV) were tested for antibodies to
      these viruses using ELISAs. Differences in HAV seroprevalence were found for
      different age groups, with a large increase in people aged 20-30 years in
      comparison with those under 20. After logistic analysis, significant differences
      were found between places of residence; the prevalence of anti-HAV was higher
      along the Maroni and Oyapock rivers than in the littoral area. The ethnic
      differences that were observed were generally due to differences in residence. Of
      all sera, 5.3% were positive for anti-HCV in preliminary tests, but only 1.5%
      remained positive after confirmation. Brazilians were significantly more
      frequently infected by HCV than other ethnic groups (4.7%). Sixty-four sera
      (6.4%) had antibodies to HEV, and differences were found between ethnic groups.
      Persons of ethnic groups who had emigrated recently to French Guiana had
      significantly higher seroprevalence rates: 14.6% for Chinese and Hmongs [odds
      ratio (OR), 4.4; 95% confidence interval (CI), 1.8-10.7], 13.5% for Brazilians
      (OR, 4.1; CI, 1.8-9.4), and 10.6% for Haitians (OR, 3.1; CI, 1.1-8.7).

PMID- 9260694
TI  - Human papillomavirus antibody responses among patients with incident cervical
      carcinoma.
AB  - The human papillomavirus (HPV) is recognized as a major cause of cervical cancer
      precursor lesions. HPV serology is a key method in the continuing elucidation of
      the importance of HPV exposure for cancer development and in predicting HPV
      associated diseases. To extend previous HPV serological studies on cervical
      cancer, serum samples from a consecutive series of 216 women with incident
      untreated cervical carcinoma and 243 age- and sex-matched healthy blood donors
      were evaluated for the presence of antibodies against HPV capsids, a marker of
      past or present HPV exposure, as well as against several cervical cancer
      associated defined HPV epitopes. Among the capsid antibody responses, HPV type 16
      seropositivity had the strongest association with cervical cancer (OR 2.7, 95% CI
      1.8-4.2), but HPV 18 and HPV 33 seropositivities were also significantly
      associated with cervical cancer (OR 1.6, 95% CI 1.1-2.5; and OR 1.5, 95% CI 1.0
      2.2, respectively). The antibody responses against the defined HPV epitopes were
      confirmed to be associated with cervical cancer, at ORs ranging from 1.4 to 2.0.
      In conclusion, the study confirms that antibodies against defined HPV epitopes
      are associated with cervical cancer and provides evidence that seropositivities
      for HPV types 16, 18, and 33 are associated with cervical cancer risk.

PMID- 9260695
TI  - Serological and molecular analysis of hepatitis C virus envelope regions 1 and 2
      during acute and chronic infections in chimpanzees.
AB  - Acute and chronic Hepatitis C virus infections were investigated retrospectively
      in chimpanzees that had been infected from a single source. Anti-E1 and anti-E2
      were detected in two of three chimpanzees with a chronic infection, but were
      first detected 1 to 2 years after inoculation. Sequence evolution of the E1
      region in three animals over a period of 9 to 11 years revealed a mutation rate
      of 1.02 to 2.23 x 10(-3) base substitutions per site per year. The acute phase
      viremia levels in acute infections which resolved appeared to be at least 10-fold
      higher than during the acute phase of chronic infections. During chronic
      infections, the viral load fell rapidly after the acute phase and remained at
      very low levels for several years. After 4 to 6 years, the viral load and liver
      enzymes increased again, suggesting reactivation of the infection. There was no
      clear temporal relationship between sequence evolution of the E1 region, changes
      in viral load, and the production of antibodies to the envelope proteins.

PMID- 9260696
TI  - Humoral immune response to functional regions of human cytomegalovirus
      glycoprotein B.
AB  - Sera from patients with primary human cytomegalovirus (HCMV) infections, both
      acute and convalescent phase, and from HCMV-seropositive healthy subjects were
      analyzed to determine whether the sera would recognize antigenic domains on HCMV
      glycoprotein B (gB) that function in virion infectivity and spread of virus from
      cell to cell. The intact gB molecule, amino-terminal derivatives of different
      lengths, and internal deletion derivatives were expressed in eukaryotic cells and
      reacted by immunofluorescence with the sera. All convalescent-phase sera and most
      sera from healthy seropositive individuals reacted with full-length gB and with
      an amino-terminal derivative containing 687 amino acids (aa), gB-(1-687);
      approximately half of the sera recognized an amino-terminal derivative of 447 aa,
      gB-(1-447), and one-third reacted with the shortest deletion derivative of 258
      aa, gB-(1-258). Of the acute-phase sera, 77% recognized intact gB and gB-(1-687),
      32% recognized gB-(1-447), and 14% recognized gB-(1-258). Deletion of aa 548 to
      618 dramatically reduced the percentage of reactive sera, whereas deletion of aa
      411 to 447 had a minor impact on reactivity of sera. To investigate the epitope
      specificity of human antibodies to gB, we carried out competition experiments
      between human sera with neutralizing activity and selected monoclonal antibodies
      (mAbs) to conformational epitopes on gB. We found that antibodies in human sera
      preclude syncytium formation in UB15-11 glioblastoma cells constitutively
      expressing gB and compete with certain murine mAbs that block virus entry into
      cells and transmission of infection from cell to cell. Our results show that HCMV
      immune human sera contain antibodies to functional regions on gB, and the
      abundance of these antibodies in convalescent-phase sera suggests that they may
      play a central role in limiting dissemination of virus in the host.

PMID- 9260697
TI  - Sclerotherapy for actively bleeding esophageal varices in male alcoholics with
      cirrhosis. Veterans Affairs Cooperative Variceal Sclerotherapy Group.
AB  - BACKGROUND: Male alcoholics hospitalized with actively bleeding esophageal
      varices were treated with sclerotherapy or sham sclerotherapy and the outcomes
      during the index hospitalization were compared. METHODS: The 87 patients were a
      subset of 253 patients enrolled in a prospective, randomized, single-blind,
      multicenter, controlled trial conducted in 12 VA medical centers. The patients
      (44 sclerotherapy, 43 sham therapy) were actively bleeding from esophageal
      varices at either randomization endoscopy (49) or follow-up endoscopy (38).
      Events and resource use during the index hospitalization were recorded. RESULTS:
      In 40 (91%) of the sclerotherapy and 26 (60%) of the sham therapy patients,
      bleeding was stopped during the endoscopy session (p < 0.001). During the
      hospitalization, 10 (25%) sclerotherapy and 21 (49%) sham therapy patients died
      (p = 0.04, relative risk 2.17, 95% CI [1.02, 4.61]); 9 sclerotherapy and 22 sham
      therapy patients rebled (p = 0.005). The median transfusion requirement was
      higher for sham therapy (8 vs 4 units, p = 0.001), the number of median ICU hours
      was greater (101 vs 55, p < 0.001), and more patients in this group required
      shunt surgery (6 vs 0, p = 0.01). CONCLUSION: Sclerotherapy, compared to no
      sclerotherapy, stops hemorrhage from actively bleeding esophageal varices and
      reduces use of resources. Sclerotherapy significantly increased hospital
      survival.

PMID- 9260698
TI  - Long-term follow-up of gastric variceal sclerotherapy: an eleven-year experience.
AB  - BACKGROUND: Bleeding from gastric varices is often a serious medical emergency.
      The role of endoscopy in the management of gastric variceal bleeding is still
      controversial. The types of gastric varices and their respective management
      strategies have not been identified. METHODS: Gastric varices were observed in
      209 patients with portal hypertension. Seventy-one patients (with cirrhosis 33,
      noncirrhotic 38) underwent gastric variceal sclerotherapy, 53 of these (75%) for
      gastric variceal bleeding. By use of a previously described classification,
      gastric varices were divided into gastroesophageal varices, type 1 (GOV1) and
      type 2 (GOV2), and isolated gastric varices, type 1 (IGV 1). Gastric variceal
      sclerotherapy was done every week using a combination technique of paravariceal
      and intravariceal injections with absolute alcohol. RESULTS: Emergency gastric
      variceal sclerotherapy arrested acute bleeding in 12 (66.7%) of 18 patients.
      Variceal obliteration was achieved in 43 of the 60 (71.6%) patients who underwent
      repeated elective sclerotherapy. Variceal obliteration was higher in patients
      with GOV1 (94.4%) than in those with GOV2 (70.4%) and IGV1 (41%). Rebleeding
      after elective gastric variceal sclerotherapy was seen in 5.5%, 19%, and 53%,
      respectively, in the three types of gastric varices. Gastric variceal recurrence
      was not seen during a mean follow-up of 24.2 +/- 22.9 months. Seventeen (24%)
      patients died, nearly equally from rebleeding and liver failure. CONCLUSIONS: (1)
      Sclerotherapy can effectively arrest acute gastric variceal bleeding and achieve
      gastric variceal obliteration, (2) it is more effective in patients with
      gastroesophageal varices, and (3) alternative therapies need to be evaluated for
      patients with IGV1.

PMID- 9260699
TI  - Does an open access system properly utilize endoscopic resources?
AB  - BACKGROUND: In an effort to maintain procedure volumes and control consultation
      costs, many gastrointestinal endoscopists and primary care providers have
      implemented systems of open access endoscopy. In these systems, specialists in
      digestive diseases perform endoscopy without prior consultation. The purpose of
      this study is to determine if indications for upper endoscopic procedures
      requested in an open access system conform to national practice guidelines and to
      establish the yield of diagnostic information relevant for patient care in this
      system. METHODS: Procedural indications and results for 3715 upper endoscopic
      procedures performed in an open access system were recorded in a computer
      database. The practice guideline "Appropriate Use of Gastrointestinal Endoscopy"
      (AUGE) of the American Society for Gastrointestinal Endoscopy was used to
      determine appropriateness of procedural indications. RESULTS: Eighty-four percent
      of procedures were performed for indications listed in the AUGE, and 59% resulted
      in findings relevant to patient care. Specialists requested endoscopy more
      frequently for "approved" indications than did nonspecialists (p = .004) and more
      frequently had findings relevant to patient care (p < .001). Findings relevant to
      patient care are significantly more frequent for some indications listed in the
      AUGE compared to others (p < .001). CONCLUSIONS: Adherence to practice guidelines
      can and does occur in an open access system. Specialists request endoscopy more
      frequently for appropriate indications compared to nonspecialists and have a
      higher yield of information relevant to patient care. Further refinement and
      better definition of some indications within the AUGE are needed to increase the
      clinical utility of this document.

PMID- 9260700
TI  - Prevalence of open-access gastrointestinal endoscopy in the United States.
AB  - OBJECTIVE: Open-access endoscopy allows physicians who are not
      gastroenterologists to directly schedule patients for endoscopic procedures
      without having them first seen in the gastrointestinal clinic. We sought to
      determine the prevalence of open-access endoscopy in the United States and to
      examine endoscopists' attitudes toward the practice. METHODS: Questionnaires were
      mailed to a random sample of 1500 members of the American Society for
      Gastrointestinal Endoscopy. Out of 1460 that apparently reached the endoscopist,
      577 (39.5%) were returned and analyzed. RESULTS: Of the endoscopists who
      responded, 60.5% said that they offered some form of open-access endoscopy. Open
      access endoscopy comprised less than 10% of outpatient endoscopic practice for
      48.2% of individuals who reported they offered the service; it comprised over 25%
      of practice in 19.8%. Of those doing it, the procedures offered on an open-access
      basis included esophagogastroduodenoscopy 86.0%, colonoscopy 76.5%, flexible
      sigmoidoscopy 94.3%, ERCP 7.7%, and endoscopic ultrasonography 4.3%. For
      endoscopists not offering open-access endoscopy, the most important reasons were
      concern about performing "not indicated" procedures (85.1 %), medical-legal
      issues (65.8%), and failure to believe in the concept of open-access endoscopy
      (59.6%). Attitudes toward open access endoscopy were significantly different
      among endoscopists who did and did not practice it. CONCLUSIONS: Open-access
      endoscopy, offered by more than 60% of the American endoscopists who responded to
      our survey, has become an important method of health care delivery in this
      country.

PMID- 9260702
TI  - Stigmata of hemorrhage in bleeding peptic ulcers: an interobserver agreement
      study among international experts.
AB  - BACKGROUND: Stigmata of hemorrhage predict rebleeding and outcome of patients
      with bleeding peptic ulcers. There are variabilities in reported incidences of
      stigmata and their respective rebleeding risks. We sought to study the
      interobserver agreement among experts. METHODS: Between June 1994 and July 1994,
      100 consecutive patients with bleeding peptic ulcers underwent videoendoscopy
      within 24 hours of their admissions. An edited videotape of these ulcers was
      compiled and sent to an international panel of 14 experts. They independently
      rated these ulcers exclusively into one of the six categories: spurting, oozing,
      nonbleeding visible vessel, adherent clot, flat pigmented spot, or clean based.
      Agreement between any two experts was expressed by a kappa estimate (kappa).
      Agreements over individual stigmata and a composite kappa estimate (kappa(w))
      signifying overall agreement were also computed. RESULTS: Out of the possible 91
      pairwise kappa estimates among 14 experts, 35 (38.5%) were less than or equal to
      0.40, indicating poor agreement. None of the kappa estimates was greater than
      0.75. Composite kappa estimates for individual stigmata were as follows: spurting
      kappa = 0.664, oozing kappa = 0.420, nonbleeding visible vessel kappa = 0.342,
      adherent clot kappa = 0.426, flat pigmented spot kappa = 0.393, and clean-based
      ulcer kappa = 0.371. The weighted kappa estimate was 0.426. CONCLUSION: Agreement
      between experts was poor in more than a third of occasions. Although the overall
      interobserver agreement was fair (0.4 < kappa < 0.75), agreements for nonbleeding
      visible vessels, flat pigmented spots, and clean-based ulcers were poor.

PMID- 9260701
TI  - Interobserver agreement on endoscopic diagnosis of bleeding peptic ulcers.
AB  - BACKGROUND: The aim of this prospective study was to evaluate the interobserver
      agreement of stigmata of recent hemorrhage of bleeding peptic ulcers. METHODS:
      Sixty-one consecutive adult patients were enrolled in the study and nine (three
      junior and six senior) endoscopists reviewed standardized video recordings of
      endoscopic examinations. Interobserver agreement was evaluated using the kappa
      (kappa) index, intraclass correlation coefficient, and proportion of agreement.
      Observer bias and poorly trained observers were investigated. RESULTS:
      Interobserver agreement was very good for oozing (kappa = 0.68), good for clot
      (kappa = 0.51), poor for spurting (kappa = 0.29) and visible vessels (kappa =
      0.33), and excellent for the absence of stigmata (kappa = 0.82). Observer bias
      sometimes occurred and the number of poorly trained observers was low. The kappa
      indexes were significantly better in senior than in junior investigators: 0.48 +/
      0.16 versus 0.37 +/- 0.26, respectively, p < 0.05. The agreement between the in
      vivo evaluation and video tape recordings (intraobserver agreement) was good
      (kappa = 0.60 +/- 0.19). There was no training phenomenon between the first and
      the second half of the patient group. CONCLUSIONS: The endoscopic classification
      of bleeding ulcers might be simplified by limiting grading to a few classes.
      Special attention should be paid to the training of endoscopists.

PMID- 9260703
TI  - Colonic involvement in patients with amebic liver abscess: endoscopic findings.
AB  - BACKGROUND: Amebic liver abscess is the most common form of extraintestinal
      amebiasis. Although the parasite enters the liver via the portal vein after
      invading large bowel mucosa, only 15% to 30% of patients have diarrhea. This
      study was done to evaluate colonic involvement in patients with amebic liver
      abscesses. METHODS: In a prospective study, colonoscopy was performed in 50
      patients with amebic liver abscesses and 15 control patients with acute amebic
      colitis. The findings were correlated with clinical features and ultrasonographic
      appearances. RESULTS: Most patients with amebic liver abscesses presented with
      fever and abdominal pain. Complete examination of the colon was possible in 45
      patients. Twenty six (58%) had evidence of lesions in the colon. Twenty-three of
      45 (51%) patients had a few discrete, small ulcers restricted to the right side
      of colon. Three of 45 (7%) patients with liver abscesses, who also had diarrhea
      at presentation, had larger and more numerous ulcers with inflammation of the
      surrounding mucosa of the left colon. Control patients with amebic colitis
      presented with diarrhea. Endoscopically, they all had multiple large ulcers with
      diffuse inflammation of the intervening mucosa of the left colon, similar to that
      seen in patients with liver abscess having diarrhea. CONCLUSIONS: Colonic
      involvement is common in patients with amebic liver abscess but most patients do
      not suffer from diarrhea, possibly because of very limited extent of the
      pathology that is confined mainly to the right side of colon.

PMID- 9260704
TI  - What predicts gastroenterologists' and surgeons' diagnosis and management of
      common bile duct stones?
AB  - BACKGROUND: Because the literature suggests numerous indicators of common bile
      duct stones, we undertook a systematic assessment of physicians' judgments of the
      clinical utility of eight indicators: patient age, history of jaundice, history
      of pancreatitis, levels of serum alanine aminotransferase, alkaline phosphatase,
      amylase, and total bilirubin, and common bile duct diameter on ultrasonography.
      METHODS: Random samples of 1500 gastroenterologists and 1500 surgeons were sent a
      survey asking them to indicate the importance of each potential indicator of
      common bile duct stones, the likelihood of common bile duct stones for each of
      nine clinical vignettes, and whether they would order a preoperative ERCP. An
      abbreviated survey was sent to nonrespondents. RESULTS: Although there was
      substantial variation in the importances assigned to each indicator, the most
      important indicators were serum total bilirubin and diameter of common bile duct
      on ultrasound. The best predictors of the decision to order an ERCP were
      perceived likelihood of stones and specialty. The average threshold for ordering
      an ERCP was 37%. Respondents did not differ from nonrespondents in the perceived
      importance of the eight indicators. CONCLUSIONS: The substantial variation among
      gastroenterologists and surgeons regarding the optimal approach to common bile
      duct stones has clinical implications. Patients will receive varying
      recommendations for care, depending on whom they see.

PMID- 9260705
TI  - ERCP: a review of technical competency and workload in a small unit.
AB  - BACKGROUND: ERCP is increasingly performed not only in large referral centers but
      also in smaller units. We sought to analyze the success rates of selective
      cannulation and intervention using the cumulative sum method and to document the
      workload in a small unit. METHODS: Indications, results, and interventions
      performed by one endoscopist were recorded for all patients undergoing ERCP at
      Dunedin Hospital. Selective cannulation and successful intervention were used as
      outcome measures and, using the cumulative sum method, compared to a target value
      of 90%. RESULTS: Over an 8-year period, 532 ERCPs were performed. Overall 91% and
      81% of selective cannulation and interventions respectively, were successful. The
      cumulative sum method plot shows that satisfactory outcomes for selective
      cannulation were obtained after some 100 to 120 procedures and after some 120
      interventions. ERCP was normal in 171 (32%) patients, stones were found in 169
      (32%), and strictures in 81 (15%) patients. CONCLUSIONS: The cumulative sum
      method is a valuable tool to compare individual performance with a nominated
      target value and to ensure that an acceptable outcome is achieved and maintained.
      These results show that small units can develop and maintain expertise in ERCP if
      procedures are performed regularly.

PMID- 9260706
TI  - Gastric inflammatory fibroid polyps: endoscopic ultrasonographic analysis in
      comparison with the histology.
AB  - BACKGROUND: Histologic diagnosis of inflammatory fibroid polyp is usually
      difficult on routine endoscopic examinations. The aim of this study was to
      describe endoscopic ultrasonographic features of gastric inflammatory fibroid
      polyps. METHODS: Endoscopic ultrasonography was performed in 10 patients with
      gastric inflammatory fibroid polyps before resection. All lesions were resected
      by either endoscopic removal or gastrectomy and then confirmed histologically as
      inflammatory fibroid polyps. To evaluate the diagnostic value of endosonography,
      endoscopic ultrasonographic images of the lesions were analyzed and compared with
      resected specimens retrospectively. RESULTS: All lesions were located in the
      second and/or third sonographic layer of the gastric wall without involvement of
      the fourth layer. The most frequent endoscopic ultrasonographic features were an
      indistinct margin (90%), and a hypoechoic (80%), homogeneous (90%) echo pattern.
      Histologically, inflammatory fibroid polyps developed in the deep mucosa and/or
      submucosa by proliferation of fibrous tissue, but did not have a capsule.
      CONCLUSIONS: The characteristic endoscopic ultrasonographic attributes of gastric
      inflammatory fibroid polyps are indistinct margin, hypoechogenicity, homogeneous
      appearance, and location within the second and/or third layer. These findings
      correlate very closely to the histologic findings.

PMID- 9260707
TI  - Virtual Vision for diagnostic and therapeutic esophagogastroduodenoscopy and
      colonoscopy.

PMID- 9260709
TI  - Separation of an overtube from the bite block during band ligation of esophageal
      varices.

PMID- 9260708
TI  - Detection of aberrant crypt foci by magnifying colonoscopy.

PMID- 9260710
TI  - Endoscopic resection of heterotopic pancreas of the minor duodenal papilla: case
      report and review of the literature.

PMID- 9260711
TI  - Warfarin therapy complicated by recurrent hemobilia in a patient with
      sarcoidosis.

PMID- 9260712
TI  - Endoscopic ultrasonographic characteristics of a gastric tubular duplication.

PMID- 9260713
TI  - Endoscopic removal of a "floating" biliary Gianturco Z stent five years after
      placement for a benign anastomotic stricture in a liver transplant patient.

PMID- 9260714
TI  - Management of actively bleeding esophageal varices.

PMID- 9260715
TI  - Open access endoscopy: cognition, technician, or some of both?

PMID- 9260716
TI  - The value of endoscopic ultrasonography in primary malignant melanoma of the
      esophagus.

PMID- 9260717
TI  - Risk of submucosal saline injection for colonic polypectomy.

PMID- 9260718
TI  - Per-procedure endoscopy costs.

PMID- 9260719
TI  - Rectal Dieulafoy's or angiodysplasia?

PMID- 9260720
TI  - Lack of an association of anisakiasis and inflammatory fibroid polyps.

PMID- 9260721
TI  - Quantitative breath testing does not predict the presence of peptic ulcer
      disease.

PMID- 9260722
TI  - Factors related to the failure of endoscopic injection therapy for bleeding
      gastric ulcer.

PMID- 9260723
TI  - Ultra-high magnification endoscopy of the normal esophageal mucosa.

PMID- 9260724
TI  - Preoperative endoscopic retrograde cholangiopancreatography: therapeutic impact
      in a general population of patients needing a cholecystectomy.

PMID- 9260725
TI  - Endoscopy is superfluous during insertion of expandable metal stents in
      esophageal tumors.

PMID- 9260726
TI  - Biliary stents as temporary treatment for choledocholithiasis in pregnant
      patients.

PMID- 9260727
TI  - Irreversible lithium neurotoxicity: an overview.
AB  - Lithium is widely used, and most of its side effects are well established and
      recognized. Persistent neurologic sequelae or dysfunctions are not common, but
      they are serious side effects. They usually persist after acute toxicity
      following accidental or suicidal overdose or during maintenance therapy, when
      toxicity is more insidious. The irreversible neurologic sequelae are generally
      cerebellar signs, especially ataxia and dysarthria. Risk factors are sometimes
      present and recognizable, but more often they are not well identified. Persistent
      neurologic handicaps greatly reduce the quality of life and are difficult to
      manage. Lithium toxicity can be avoided by conservative prescribing, care in
      combining drug therapies, and, above all, educating the patient and caregivers to
      recognize early signs of the condition. A review of the literature is presented,
      together with vignettes of a further seven cases.

PMID- 9260728
TI  - Serotonin, dopamine, and motor effects in Parkinson's disease.
AB  - We review recent reports suggesting that use of selective serotonergic agents
      that either inhibit synaptic reuptake or have specific serotonin receptor
      affinities may benefit a variety of motor disturbances in Parkinson's disease.
      The complex, mixed motoric effects of these agents in Parkinson's disease have
      not allowed for a consistent view on the interrelationship between dopamine and
      serotonin (5HT) in motor control but may speak to the nature of dysregulated
      neurotransmission in the disease.

PMID- 9260729
TI  - Effects of prolonged infusions of the NMDA antagonist aptiganel hydrochloride
      (CNS 1102) in normal volunteers.
AB  - Blockade of the N-methyl D-aspartate (NMDA) receptor by the ion-channel-blocking
      drug aptiganel hydrochloride (CNS 1102, Cerestat) is neuroprotective in focal
      cerebral ischemia. Short intravenous infusions of up to 30 microg/kg have been
      well tolerated by healthy male volunteers. We undertook a randomized, double
      blind, placebo-controlled study in 20 male volunteers to examine the safety,
      tolerability, and cardiovascular and psychomotor effects of a dosing paradigm
      similar to that envisaged for therapeutic use. Aptiganel HCl was infused over 4 h
      in total doses of 15, 32, 50, or 73 microg kg. Mean arterial pressure increased
      significantly with dose group (p < 0.01, analysis of covariance). Motor reaction
      time was related to maximal plasma concentration (r2 = 0.21, p < 0.001).
      Transient symptoms and signs of peripheral paresthesiae, light-headedness, and
      euphoria were seen at total doses of 32 microg/ kg. Higher doses were associated
      with motor retardation, perceptual disturbances, and hallucinations (one case).
      Clearance was 125 +/- 55 L/h, and volume of distribution was 537 +/- 1,261. Total
      doses of up to 32 microg/kg of aptiganel HCl infused over 4 h are well tolerated
      by healthy males. Aptiganel HCl causes elevation of blood pressure and is
      associated with central nervous system symptoms and signs similar to other
      noncompetitive NMDA antagonists.

PMID- 9260730
TI  - Evaluation of the Short Parkinson's Evaluation Scale: a new friendly scale for
      the evaluation of Parkinson's disease in clinical drug trials.
AB  - The extensive use of the Unified Parkinson's Disease Rating Scale (UPDRS) has
      revealed low interrater reliability in some items and redundancy in others. In
      view of these shortcomings, we have structured a new scale that includes a zero
      to three-point scale for each item in the evaluation of PD. The mental axis
      includes memory, thought disorders, and depression. Activities of daily living
      (ADL) includes eight items: speech, eating, feeding, dressing, hygiene,
      handwriting, walking, and turning in bed. The motor examination includes eight
      items: speech, tremor, rest and posture, rigidity, finger tapping, arising from
      chair, gait, and postural stability. Complications of therapy were also included:
      dyskinesias, dystonia, motor fluctuations, and freezing episodes, collected by
      history. In addition, a global scoring for motor fluctuations that should
      complement the Hoehn and Yahr Scale was incorporated. In this report, we present
      a statistical analysis of the ADL, motor evaluation, and complications of therapy
      sections. Concerning the interrater reliability mean, Kendall's W values were
      >0.9 for most of the items in the Short Parkinson's Evaluation Scale (SPES).
      Kendall's W <0.8 (motor evaluation) was found for two items of the SPES and nine
      items of the UPDRS. The mean interrater reliability for both scales across all
      seven centers (seven Kendall's W for seven centers) (Mann-Whitney test) showed no
      statistical differences between the scales. Spearman's correlations between items
      of both scales were significant. Factor analysis of the SPES and UPDRS data
      revealed a four-factor solution that explained approximately 60% of the data. All
      participating centers found the SPES easier to apply and quicker to complete,
      when compared with the UPDRS. The results obtained strongly favor the
      introduction of SPES for clinical practice.

PMID- 9260731
TI  - Treatment of Alzheimer's disease with sabeluzole: functional and structural
      correlates.
AB  - Sabeluzole, a new benzothiazole derivative, has been shown to be
      neurobiologically active preclinically and clinically appears to exert beneficial
      effects on memory. In this study, sabeluzole (5 or 10 mg twice daily vs. placebo)
      was investigated in patients with probable Alzheimer's disease over 1 year, with
      assessments of cognitive performance and structural changes. Cognitive
      performance was measured using the Alzheimer's Disease Assessment Scale
      periodically during treatment. Potential structural correlates in the frontal
      horn, caudate, third ventricle and hippocampal regions were examined by obtaining
      computerized tomographic (CT) images before and after treatment. Patients
      receiving sabeluzole evidenced greater stability than did placebo-treated
      patients in some cognitive measures. CT measures showed no significant changes
      from baseline, but some weak associations were found between relative
      preservation of cognitive function and smaller structural declines in the third
      ventricle and hippocampus. Cognitive outcome measures suggest that sabeluzole may
      have potential in slowing the cognitive deterioration of Alzheimer's disease.
      Furthermore, the method used to explore potential benefits on a morphologic
      level, although negative in this study, could yet have potential.

PMID- 9260732
TI  - Phenytoin kinetics in Japanese adult epileptics: phenotype of phenytoin slow
      metabolizers.
AB  - Phenytoin pharmacokinetics in 18 of 126 Japanese epileptic patients were
      investigated using the Michaelis-Menten equation. Five of these (4% of total)
      patients, who showed significantly high plasma concentrations of phenytoin even
      when administered a relatively low daily dose of phenytoin, were classified as
      slow metabolizers; 13 of these, who showed lower plasma concentrations, were
      classified as normal metabolizers. Comparison of slow and normal metabolizers
      revealed that the maximum rate of metabolism, Vmax, differed significantly
      between the two groups, the borderline Vmax value between the two groups being
      approximately 4.5-4.8 mg/kg/day. The mean Vmax value of slow metabolizers was
      calculated to be 70% that of normal metabolizers. It is possible that one means
      of phenotyping slow and normal phenytoin metabolizers is by analysis of phenytoin
      pharmacokinetics, with estimation of Vmax values.

PMID- 9260733
TI  - Clozapine induced polyserositis.
AB  - Clozapine was approved by the U.S. Food and Drug Administration in 1989 for
      treatment of severely ill schizophrenic patients. It has activity against both
      the positive and negative symptoms of schizophrenia, which has made it an
      alternative to traditional antipsychotic medications such as haloperidol.
      However, clozapine must be used cautiously due to its side effect profile. These
      side effects include agranulocytosis, seizures, and cardiorespiratory symptoms.
      We report the case of a patient who developed polyserositis (pericardial
      effusion, pleural effusion, and pericarditis) after being started on clozapine,
      and whose symptoms remitted upon discontinuation of clozapine. The literature is
      reviewed and the treatment implications are discussed.

PMID- 9260734
TI  - Methylene blue adjuvant therapy of schizophrenia.
AB  - There is growing interest in the role of the nitric oxide (NO) pathway in
      idiopathic psychotic disorders such as schizophrenia. In this preliminary study,
      we examined the therapeutic efficacy of methylene blue (MB), a "downstream"
      inhibitor of one of NO's actions, administered orally as an adjuvant to
      conventional neuroleptic medications. Specifically, MB blocks NO's activation of
      soluble guanylyl cyclase. MB has previously been reported to have therapeutic
      effects in the treatment of psychosis and mania. Preclinical data also suggest
      that MB might possess antipsychotic potential. Participants in the current study
      were eight patients with schizophrenia who had incomplete responses to
      conventional antipsychotics (as evidenced by a Brief Psychiatric Rating Scale
      [BPRS] total score of 35 or more). These patients completed a 4-week open-label
      study with a 1 week "off", 2 week "on", and one final week "off" design. Measures
      of treatment efficacy were the BPRS, Schedule for the Assessment of Negative
      Symptoms, and Clinical Global Improvement Scale administered weekly. Final scores
      for each outcome measure item were based on the consensus of at least two trained
      raters present during each rating interview. A statistically significant, albeit
      modest, decrease in the severity of psychopathology was observed while the
      subjects were taking MB, and psychopathology significantly worsened when MB was
      discontinued. The results suggest a need for further study with MB or perhaps
      other NO-dependent guanylyl cyclase-inhibiting medications.

PMID- 9260735
TI  - Effects of nifedipine, a calcium channel antagonist, on cognitive function in
      schizophrenic patients with tardive dyskinesia.
AB  - We examined whether nifedipine, a calcium channel antagonist, added to a stable
      regimen of neuroleptic medication would affect cognition in patients with chronic
      schizophrenia or schizoaffective disorder who had tardive dyskinesia. Fifteen
      patients with tardive dyskinesia were treated with nifedipine (60 mg daily) or
      matching placebo for 4 weeks and then were crossed over from nifedipine to
      placebo or from placebo to nifedipine for another 4 weeks. At the end of each 4
      week phase of the study, the patients performed a rotary pursuit test of
      procedural learning and a dementia scale assessing general cognitive abilities.
      Nifedipine improved performance in the rotary pursuit test and conceptual
      abilities in the dementia scale compared with placebo, but only for patients who
      first were exposed to the tests during the placebo condition. These results
      provide preliminary evidence that calcium channel antagonists might enhance
      learning and memory in schizophrenic patients with tardive dyskinesia.

PMID- 9260736
TI  - Result of long-term administration of L-threo-3,4-dihydroxyphenylserine in
      patients with pure akinesia as an early symptom of progressive supranuclear
      palsy.
AB  - Results of long-term administration of L-threo-3,4-dihydroxyphenylserine (L
      DOPS), a synthetic precursor of noradrenaline, in a patient with freezing gait
      and pure akinesia are reported. Effects were temporal and disappeared during a 16
      month treatment period. It was recognized that pure akinesia is an early symptom
      of progressive supranuclear palsy (PSP). Previously, we reported results of short
      term (4 weeks) administration of L-DOPS in this patient. We present the further
      clinical course of the patient, along with results of long-term (16 months)
      administration of L-DOPS.

PMID- 9260737
TI  - NCAM 180 in the postnatal development of cat visual cortex: an
      immunohistochemical study.
AB  - The neural cell adhesion molecule (NCAM) consists of three major isoforms with
      differing extents of intracellular domains. The largest, NCAM 180, may play an
      important role in the development and stabilization of cell contacts because of
      its interaction with the cytoskeleton, its accumulation at contact sites between
      cells, and age-dependent modifications of the immunoreactivity of its
      intracellular domain. The developmental expression pattern of NCAM 180 was
      examined in the cat visual cortex to explore its relation with the age-dependent
      decline of synaptic malleability. Western blot and immunohistochemical analyses
      were carried out by using a monoclonal antibody (D3) directed against an epitope
      of the intracellular domain specific to NCAM 180 and antibodies against all NCAM
      isoforms. The latter revealed a similar time course of increased expression
      during development by both Western blot and immunohistochemical analysis. In
      contrast, the D3 antibody showed an age-dependent increase of immunoreactivity by
      Western blot analysis and a decrease of reactivity by immunohistochemistry. In
      addition, the D3 antibody revealed characteristic developmental changes of
      immunoreactivity in the neuropil and distribution of immunopositive neuronal cell
      bodies in the different cortical laminae. The observations from this and another
      study (Kramer et al., 1997) suggest that the D3 antibody-specific NCAM 180
      epitope is masked during the stabilization of connectivity.

PMID- 9260739
TI  - BDNF/NT4-5 receptor TrkB and cadherin participate in cell-cell adhesion.
AB  - The neurotrophin receptor TrkB plays a key role in promoting cell survival and
      differentiation in the nervous system. Two adhesive motifs in the extracellular
      domain of TrkB have been proposed based on its predicted secondary structure. To
      investigate the potential adhesive function of trkB, a full length trkB cDNA was
      stably transfected into NIH 3T3 cells and TrkB-expressing clones isolated.
      Transfectant clones producing different levels of TrkB protein were subjected to
      a homotypic aggregation assay. Results showed that parental cells were non
      adhesive during the assay while TrkB-expressing cells displayed varying degrees
      of aggregation depending on the amount of TrkB protein expressed. The observed
      adhesion was Ca(2+)-, Mg(2+)-, and temperature-dependent, characteristics shared
      by the cadherin family of adhesion molecules. The transfected cell lines also
      expressed cadherin in proportion to TrkB expression and both molecules were
      required for cell adhesion. Double immunofluorescence staining studies showed
      that TrkB was colocalized with cadherin and catenin at cell-cell contact sites.
      Whether TrkB and cadherin mediate adhesion separately or synergistically remains
      to be determined.

PMID- 9260738
TI  - Blood-retinal barrier (BRB) breakdown in experimental autoimmune uveoretinitis:
      comparison with vascular endothelial growth factor, tumor necrosis factor alpha,
      and interleukin-1beta-mediated breakdown.
AB  - Experimental autoimmune uveoretinitis (EAU) induced in Lewis rats by immunization
      with S-antigen is a model of human uveitis. By using immunocytochemical staining
      for albumin, relatively minor blood-retinal barrier (BRB) breakdown was initially
      shown in the peripheral retina 8 days after immunization and in the posterior
      retina by 10 days. Albumin extravasation appeared to occur by opening of the
      retinal vascular endothelial (RVE) and the retinal pigmented epithelial (RPE)
      tight junctions, by transendothelial vesicular transport, and by permeating
      damaged RVE cells. Each of three anti-inflammatory agents reduced or delayed
      autoimmune-mediated cell destruction but did not eliminate any particular route
      of extravasation. Vascular endothelial growth factor (VEGF), tumor necrosis
      factor alpha (TNF alpha), and interleukin-1beta (IL-1beta) are intimately
      associated with the development of EAU and are capable of causing BRB
      dysfunction. A high percentage of RVE tight junctions appeared open
      ultrastructurally after intravitreal injection of VEGF (26.7%), TNF alpha
      (35.6%), or IL-1beta (22.1%) compared with saline-injected control (11.4%) or
      normal, untreated rabbits (4.1%). Heat treatment abolished the effect of IL-1beta
      on the BRB but only partially reduced the effect of VEGF. By 24 hr after
      injection, the effect of TNF alpha had reversed, but that of IL-1beta had not;
      VEGF-mediated BRB dysfunction was partially reversible. In addition, albumin
      filled vesicle-like structures were seen in the RVE cytoplasm following treatment
      with each mediator. This study shows that VEGF, TNF alpha, and IL-1beta each
      cause BRB breakdown by opening tight junctions between RVE cells and possibly by
      increasing transendothelial vesicular transport. Each of these agents may
      contribute to BRB breakdown in EAU and in patients with uveitis.

PMID- 9260740
TI  - Reorientation of prostanoid production accompanies "activation" of adult
      microglial cells in culture.
AB  - Using morphological, immunocytochemical, and functional parameters we have
      previously shown that highly purified adult rat microglial cells undergo a
      process of "activation" when cultured in a serum-containing medium in the absence
      of added proinflammatory substances or other factors (Slepko and Levi: Glia
      16:241-246, 1996). Here we studied the lipopolysaccharide (LPS)-evoked production
      of two prostanoids, thromboxane A2 (measured as thromboxane B2) (TXB2) and
      prostaglandin E2 (PGE2), as a function of microglial "activation." LPS induced a
      greater time- and dose-dependent release of TXB2, compared to PGE2, in the less
      "activated" cells. Further "activation" led to amplified synthesis of PGE2 and
      not of TXB2, so that the TXB2/PGE2 ratio changed from 2.2 to 0.25 between the 2nd
      and 4th day in culture. Western blot experiments showed that the LPS-evoked
      expression of the inducible form of cyclooxygenase (COX) was markedly higher in
      cells exhibiting a more "activated" phenotype. The expression of the constitutive
      isoform of COX was low in all conditions, was slightly greater in more
      "activated" cells, and was not affected by LPS. Neither progression in microglial
      "activation" nor LPS treatment enhanced thromboxane synthase activity. We
      hypothesize that reorientation of prostanoid synthesis toward a major production
      of PGE2 in the more "activated" cells can be largely attributed to an increased
      inducibility of cellular COX expression, combined with the inability of
      thromboxane synthase to cope with the increased availability of the COX product
      prostaglandin H2 (PGH2), the common precursor of TXA2 and PGE2. In view of the
      different, and at times opposite, functional activity of TXB2 and PGE2, the
      described change in prostanoid production pattern may contribute to the role of
      "activated" microglia in inflammation and host defense.

PMID- 9260741
TI  - In vivo protection of striatal dopaminergic system against 1-methyl-4
      phenylpyridinium neurotoxicity by phenobarbital.
AB  - We have studied the effect of a semichronic and acute treatment of phenobarbital
      on in vivo 1-methyl-4-phenylpyridinium ion- (MPP+)-induced neurotoxicity. A group
      of rats were intraperitoneally injected for 12 days with phenobarbital (80 mg/Kg
      of body weight, semichronic treatment) in order to induce cytochrome P450 levels
      in brain. At day 10 of treatment, rats received unilateral left striatal
      injections of 1 or 2 microg of MPP+. Two days after the injection of the toxin a
      dose-dependent loss of dopamine uptake along with a concomitant decrease of
      dopamine levels and its metabolites was produced in control rats. In
      phenobarbital treated animals striatal injection of 1 microg of MPP+ did not
      produce any effect on dopaminergic parameters but injection of 2 microg of MPP+
      caused losses of dopamine levels and dopamine transporter although smaller than
      in control rats. TH immunohistochemistry in semichronic phenobarbital treated
      rats also demonstrated the protective effect of this drug against MPP+ toxicity.
      Dopamine uptake in synaptosomes from semichronic phenobarbital treated rats did
      not change with respect to the controls, thereby diminished MPP+ toxicity in
      phenobarbital treated rats is not due to an alterated uptake of the toxin.
      Neuroprotection found by intraperitoneal injection of phenobarbital 30 min before
      MPP+ intrastriatal injection (acute treatment) could discard the induction of
      cytochrome P450 as responsible for this suppressed neurotoxicity of MPP+. The
      neuroprotective effect of phenobarbital could be produced by its action as an
      excitatory amino acid antagonist or as a GABA agonist.

PMID- 9260742
TI  - Glutamate toxicity enhances tau gene expression in neuronal cultures.
AB  - Tau protein is a microtubule-associated protein normally expressed in neurons. In
      Alzheimer's disease (AD) brains, phosphorylated tau accumulates in paired helical
      filaments which form neurofibrillary tangles in affected neurons; moreover, tau
      mRNA expression is increased in affected regions of AD brains. Glutamate, an
      excitatory neurotransmitter but also a potent neurotoxin under pathologic
      conditions, is known to produce neuronal degeneration and death accompanied by an
      increase in tau immunoreactivity in primary neuronal cultures. The goal of the
      present study is to evaluate the effects of glutamate on tau gene expression in
      neuronal cultures. We report a delayed and long-lasting enhancement of tau mRNA
      expression after a 15 min exposure to toxic concentrations of glutamate: neuronal
      tau mRNA levels reach a peak after 3 hr and remain increased 6 and 12 hr after
      the end of glutamate exposure. Both NMDA and AMPA/ kainate receptors are involved
      in this tau gene overexpression. Actinomycin D prevents this tau mRNA induction
      indicating that transduction signals elicited by glutamate act at the
      transcriptional level. The role of this delayed tau overexpression is not
      elucided but could be linked to either a reactive survival process or to a
      programmed cellular degeneration.

PMID- 9260743
TI  - Differential regulation of microtubule-associated protein 1B (MAP1B) in rat CNS
      and PNS during development.
AB  - MAP1B is a major cytoskeletal protein in growing axons and is strongly regulated
      during brain development. The present studies compare the expression of MAP1B
      mRNA, the protein, and its phosphorylated isoform in spinal cord and dorsal root
      ganglia (DRGs) with brain. In spinal cord and brain, MAP1B mRNA levels were
      highest in early stages of development, decreased several fold during postnatal
      development, and remained low in adults. In contrast, there were no significant
      changes of MAP1B mRNA levels during development of DRG and they remained high in
      adults. The levels of MAP1B protein decreased in brain and spinal cord in
      parallel with the changes of their mRNA. The protein levels in DRG remained
      relatively high but declined in the sciatic nerve. Phosphorylated MAP1B was
      expressed in high levels during the early stages of development in brain, spinal
      cord, and sciatic nerve and decreased rapidly to undetectable levels postnatally
      except for sciatic nerve where it remained detectable. Immunohistochemical
      analysis showed that phosphorylated MAP1B was absent from DRG cell bodies at all
      stages but was present in axons of DRG and motor neurons in both spinal cord and
      sciatic nerve. Immunostaining also confirmed Western blot analysis indicating
      that MAP1B was initially abundant within the spinal cord but was at later stages
      present only in motor neurons and the central processes of DRG neurons. These
      results reflect differential distribution of MAP1B isoforms at different stages
      of development and in different regions of the nervous system.

PMID- 9260744
TI  - Regulation by calcium of the nitric oxide/cyclic GMP system in cerebellar granule
      cells and astroglia in culture.
AB  - Ca2+ entry induced by N-methyl-D-aspartate (NMDA) in neurons and by noradrenaline
      (NA) in astrocytes is known to increase intracellular cyclic GMP (cGMP) levels
      through stimulation of the Ca2+-dependent nitric oxide synthase type I (NOS-I).
      The possibility that Ca2+ entry could also down-regulate intracellular cGMP by
      activating a Ca2+/calmodulin-dependent phosphodiesterase (CaM-PDE) has been
      investigated here in primary cultures enriched in granule neurons or in astroglia
      from rat cerebellum. We show that the same agonists that stimulate nitric oxide
      (NO) formation (NMDA and NA at 100 microM) and the Ca2+ ionophore A23187 (10
      microM) decrease cGMP generated in response to direct stimulation of soluble
      guanylyl cyclase (sGC) by NO donors in both cell types. This effect requires
      extracellular Ca2+ and is prevented by the calmodulin inhibitor W7 (100 microM).
      Membrane depolarization, manipulations of the Na+ gradient, and intracellular
      Ca2+ mobilization also decrease NO donor-induced cGMP formation in granule cells.
      In astroglia Ca2+ entry additionally down-regulates cGMP generated by stimulation
      of the particulate GC by atrial natriuretic peptide (ANF). Decreases in cGMP
      produced by A23187 were more pronounced in the absence than in the presence of
      the PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX; 1 mM), indicating that a CaM
      PDE was involved. We also show that astroglial cells can accumulate similar
      amounts of cGMP than neurons in response to NO donors when IBMX is present but
      much lower levels in its absence. This may result from a lower ratio of sGC to
      PDE activities in astroglia.

PMID- 9260745
TI  - Establishment of human adult astrocyte cultures derived from postmortem multiple
      sclerosis and control brain and spinal cord regions: immunophenotypical and
      functional characterization.
AB  - We have successfully established highly enriched astrocyte cultures upon
      passaging of primary cultures derived from various regions of postmortem human
      adult brain and spinal cord. Tissues were collected at autopsies with relatively
      short postmortem times (3-9 hr) from multiple sclerosis (MS) and (normal) control
      cases. Immunocytochemical analysis showed that primary cultures were composed of
      colonies of oligoclonal cells that expressed the intermediate filament proteins
      glial fibrillary acidic protein (GFAP), vimentin, as well as glutamine synthetase
      (GS). Passaging the astrocytes did not affect their proliferating capacity as
      monitored by bromodeoxyuridine (BrdU) incorporation. Astrocyte-specific markers
      were stably expressed for at least 12 passages per individual tissue sample.
      Large numbers of GFAP-positive astrocytes were obtained from each sample and
      could be stored frozen and recultured. Very few macrophages/microglial cells (1
      3%) were present in the human adult astrocyte cultures, using a panel of
      macrophage-specific markers. However, the monoclonal antibodies (mAbs KP1, EBM1,
      25F9) and lysozyme antiserum directed against lysosomal antigens strongly
      immunostained cultured astrocytes derived from MS and control cases, implicating
      that expression of these lysosomal antigens is not restricted to macrophages/
      microglial cells in human glial cell cultures. Interestingly, astrocytes derived
      from active demyelinated MS lesions showed an increased proliferating capacity
      compared to astrocytes derived from non-lesioned and normal brain and spinal cord
      regions, as shown with a microculture tetrazolium assay (MTT assay).

PMID- 9260746
TI  - NGF and BDNF in the anterior pituitary lobe of adult rats.
AB  - Previous studies revealed that NGF-like immunoreactivity is present in cells from
      the adult rat anterior pituitary lobe, both in vivo and in vitro, and that in
      both situations NGF colocalizes with the thyroid-stimulating hormone (TSH). More
      recently, brain-derived neurotrophic factor (BDNF) was similarly found to occur
      in the anterior pituitary tissue, again with a general colocalization with TSH.
      In the present study, we have extended the use of adult rat anterior pituitary
      cultures to show their content of BDNF-immunoreactive cells and their main
      colocalization with TSH. We have also explored the question of whether
      neurotrophins nerve growth factor (NGF) and/or BDNF are actually produced within
      anterior pituitary cells. Use of the sensitive method reverse transcription
      polymerase chain reaction (RT-PCR) has allowed us to confirm the presence of NGF
      and BDNF mRNAs in the cell suspension freshly derived from adult anterior
      pituitary. In situ hybridization techniques applied to the cell cultures from
      such a suspension, however, have revealed only a variable presence of NGF mRNA
      positive cells but no recognizable BDNF mRNA. Thus, the question of whether the
      two neurotrophins are produced within the very cells whose immunoreactive content
      can be recognized remains an open one.

PMID- 9260747
TI  - MK-801 neurotoxicity in the guinea pig cerebral cortex: susceptibility and
      regional differences compared with the rat.
AB  - N-methyl-D-aspartate (NMDA) receptor antagonists induce transient vacuole
      formation in neurons of the retrosplenial cortex and, after higher doses,
      necrosis in the same region. To our knowledge, all studies demonstrating these
      effects have been carried out in rats or mice. The present study investigated
      whether vacuolization occurs in the guinea pig, rats being used as controls.
      Female Dunkin-Hartley guinea pigs (age 15-18 weeks) were given a single
      subcutaneous injection of saline or the non-competitive NMDA antagonist
      dizocilpine maleate [(+)-MK-801; 1, 4, or 12 mg/kg]. Female Sprague-Dawley rats
      (age 16 weeks) received saline or MK-801 (1 mg/kg). Whatever the dose of MK-801,
      guinea pigs showed only occasional vacuolated neurons in the retrosplenial
      cortex. However, affected neurons (mainly large pyramidal cells of layer V) were
      found in the frontoparietal neocortex. The reaction was limited after 1 mg/kg,
      and seemed to reach a maximum at 4 mg/kg. Rats injected with 1 mg/kg MK-801
      showed an intense vacuole reaction in neurons from layers III-IV of the
      retrosplenial cortex, but no affected neurons were noted in neocortical areas. We
      conclude that there are significant species differences in susceptibility to, and
      location of, vacuolization induced by NMDA receptor antagonists.

PMID- 9260748
TI  - Lipid composition and phospholipid asymmetry of membranes from a Schwann cell
      line.
AB  - We report the total lipid composition and phospholipid asymmetry of a plasma
      membrane preparation isolated from a Schwann cell line (NF1T) derived from a
      human neurofibroma. The specific activities of three plasma membrane markers (5'
      nucleotidase, Na-K-ATPase, and CNPase) were 8-fold, 12-fold, and 16-fold higher,
      respectively, in the plasma membrane fraction compared to the specific activities
      found in the total homogenate. The specific activities of the marker enzymes of
      intracellular membranes in the isolated plasma membrane fraction indicated little
      contamination with intracellular organelles. The enrichment of cholesterol (3
      fold), sphingomyelin (3-fold), and glycolipids (cerebrosides 8-fold, sulfatides 5
      fold) also indicated a high degree of purity of the plasma membrane fraction. The
      high content of phosphatidylinositol and phosphatidylcholine (10% and 44% of
      total phospholipid) and the low phosphatidylserine and phosphatidylethanolamine
      content (3% and 14% of the total phospholipid) were also characteristic of the
      plasma membrane fraction derived from this cell line. The transbilayer
      phospholipid distribution of the plasma membrane in intact cells and in the
      isolated plasma membrane fraction was investigated by using phospholipase A2 (bee
      venom) and sphingomyelinase (S. aureus). The phospholipid asymmetry of NF1T
      plasma membrane followed the general features of phospholipid asymmetry in
      eukaryotic cells: sphingomyelin and phosphatidylcholine were preferentially
      located in the outer leaflet (90% and 89%, respectively) while the
      aminophospholipids phosphatidylethanolamine, phosphatidylserine, and
      phosphatidylinositol were in the inner half of the membrane (85%, 96%, and 69%,
      respectively). A high percentage of the total plasma membrane
      phosphatidylinositol (31%) was found in the outer side of the membrane indicating
      a decreased asymmetric distribution for this negatively charged phospholipid. The
      phospholipid asymmetry found in the plasma membrane vesicle fraction corroborated
      the phospholipid asymmetry of the intact cells, thus confirming that the plasma
      membrane vesicles maintained the original orientation and lipid asymmetry after
      homogenization and/or sonication.

PMID- 9260749
TI  - Variants of the receptor/channel clustering molecule gephyrin in brain: distinct
      distribution patterns, developmental profiles, and proteolytic cleavage by
      calpain.
AB  - The postsynaptic molecule gephyrin is involved in clustering neurotransmitter
      receptors. To test for protein variants that correspond to alternatively spliced
      gephyrin mRNAs, antibodies were made against 1) an amino-terminal domain of
      gephyrin (GN(N)) and 2) its invariant carboxy-terminus (GN(C)). Both antibodies
      recognized an antigen with the expected molecular weight of 93-95 kDa in rat and
      human brain tissue, as well as five additional proteins between 90 and 108 kDa.
      Most of these variants were found distributed throughout the brain, and their
      developmental profiles paralleled those of synaptic markers. Interestingly, the
      pattern of antigens immunostained across brain regions by anti-GN(N) was markedly
      distinct from that labeled by anti-GN(C), a difference consistent with carboxy
      terminal modification. In control experiments in which hippocampal membranes were
      treated to activate endogenous proteases, there was no evidence that certain
      gephyrin variants originate from proteolysis. A subset of the antigens was,
      however, rapidly degraded during the treatment. A corresponding production of
      stable, carboxy-terminal gephyrin fragments of 48-50 kDa occurred within 1 min of
      proteolytic activation and was blocked by the selective calpain inhibitor CX295.
      These findings suggest that multiple gephyrin proteins are active in the brain
      and that some of their roles may require functional modulation by limited
      proteolysis.

PMID- 9260751
TI  - Value-based surgical pathology: a valuable concept.

PMID- 9260750
TI  - Cholesterol reutilization during myelination of regenerating PNS axons is
      impaired in Niemann-Pick disease type C mice.
AB  - Niemann-Pick C (NPC) disease is an autosomal recessive lipidosis characterized by
      lysosomal accumulations of unesterified cholesterol. Cultured NPC cells exhibit a
      defect in the intracellular trafficking of LDL-derived cholesterol that leads to
      lysosomal accumulations of unesterified cholesterol. We found in a preliminary
      study that the myelination of regenerating axons was retarded in the NPC mouse
      following sciatic nerve crush. Because lipoprotein-mediated cholesterol transport
      is involved in myelination during nerve regeneration, we investigated whether
      this cholesterol reutilization pathway was perturbed in the NPC mouse. Mice
      received intraneural injections of [3H]acetate to label myelin cholesterol, and 2
      weeks later the injected nerves were crushed above the injection site. Four weeks
      after crush, the nerves were examined by electron microscopic autoradiography. In
      normal mice, regeneration was well advanced, with thick myelin sheaths
      surrounding the regenerated axons and very little myelin debris remaining. The
      new myelin sheaths were well labeled, indicative of efficient cholesterol
      reutilization. In NPC mice, the new myelin sheaths were thinner and contained
      little label, indicative of retarded regeneration and little or no cholesterol
      reutilization. These data suggest the possibility of a causal link between
      compromised cholesterol reutilization and delayed or slowed regeneration of
      myelin sheaths.

PMID- 9260752
TI  - Transient erythroblastopenia of childhood associated with human herpesvirus type
      6, variant B.
AB  - Transient erythroblastopenia of childhood (TEC) is a disorder of young children
      ages 3 months to 4 years that is characterized by anemia associated with
      reticulOcytopenia and decreased red blood cell precursors in the bone marrow
      aspirate (BMA). A viral cause has been suspected for TEC. Bone marrow aspirate
      derived DNA from 14 children with anemia or another hematologic disorder,
      including two children with TEC, were analyzed by polymerase chain reaction for
      human herpesvirus type 6 (HHV-6) DNA and human parvovirus B19 DNA. Testing
      revealed an HHV-6 variant B DNA in both children with TEC but not in the children
      who did not have TEC. The BMAs from these two children contained large
      pronormoblasts and an extensive lymphoid infiltrate. We proposed that HHV-6 may
      be a causative agent of TEC in immunocompetent children. This hypothesis is based
      on the demonstrated ability of HHV-6 to suppress the formation of burst-forming
      units-erythroid (BFU-E) and granulocyte macrophage-colony-forming units (GM-CFU)
      in vitro, and in vivo in HHV-6-infected patients who undergo bone marrow
      transplantation.

PMID- 9260754
TI  - The value of transformed lymphocyte count in subclassification of non-Hodgkin's
      lymphoma by fine-needle aspiration.
AB  - No established criteria exist for predicting lymphoma grade or transformation in
      cytologic material. We counted transformed lymphocytes in fine-needle aspiration
      (FNA) biopsy specimens to determine whether the percentage of these cells in the
      smear could predict the histologic grade, the biologic behavior, or both. The
      percentage of transformed lymphocytes out of total lymphoid cells was determined
      on Papanicolaou-stained smears. Afterward, a cytodiagnosis was based on clinical
      information available at the time of the FNA, cytomorphologic data, and flow
      cytometry data. Results were correlated with results of examination of the
      surgical biopsy specimen, clinical behavior of the lymphoma, or both. The
      percentage of transformed lymphocytes was 10% or less in all low-grade or
      indolent lymphomas. Aspirates with transformed lymphocyte counts of 20% or
      greater were aggressive lymphomas. We also report our experience in the diagnosis
      of non-Hodgkin's lymphoma by FNA using cytomorphologic examination and
      immunophenotyping by flow cytometry at a cancer referral hospital. This is a
      preliminary study, and larger series may help establish the ranges of transformed
      lymphocyte counts that correlate with the lymphoma subtype.

PMID- 9260753
TI  - Reticulocyte hemoglobin: an integrated parameter for evaluation of erythropoietic
      activity.
AB  - Traditional reticulocyte counts provide only a partial estimate of the
      erythropoietic bone marrow activity and do not account for qualitative variations
      of reticulocyte cellular indexes and hemoglobin content in particular. We have
      studied a new integrated parameter, reticulocyte hemoglobin (retHb), that
      quantifies in grams per liter the hemoglobin contained in the circulating
      reticulocyte compartment and is obtained by multiplying the absolute reticulocyte
      count and the reticulocyte cell hemoglobin content. In 50 normal control
      subjects, retHb values were 1.76 +/- 0.59 g/L. The retHb values were lower in
      patients double heterozygous for HbS and HbC (SC disease) (3.33 +/- 1.52 g/L, n =
      13) compared with homozygous HbS disease (SS) with concomitant alpha-thalassemia
      (5.27 +/- 1.51 g/L and 5.48 +/- 1.06 g/L for 12 patients with 3 alpha-genes and 3
      patients with 2 alpha-genes, respectively) and to SS disease with no alpha
      thalassemia (6.47 +/- 3.05, n = 20). The hemoglobin contained in the red blood
      cell pool (rbcHb) also can be calculated by subtracting retHb from the total
      hemoglobin. The ratio between the two pools (rbcHb/retHb, normal value 76.6 +/-
      21.9, n = 50) provides a rough estimate of red blood cell survival. It was 9.8 +/
      4.1 in SS disease, 16.2 +/- 10.1 and 14.7 +/- 5.0 in SS disease with 3 and 2
      normal alpha-genes, respectively, and 36.6 +/- 17.8 in SC disease with no alpha
      thalassemia. We also studied retHb in patients receiving hydroxyurea therapy for
      SS disease, intravenous or oral iron for iron deficiency, or recombinant human
      erythropoietin (r-HuEPO) therapy. All these conditions are characterized by
      changes in reticulocyte counts and marked variations in reticulocyte cellular
      hemoglobin contents, which can be integrated into the retHb parameter.
      Measurement of retHb and the rbcHb/retHb ratio may provide an estimate of the
      reduction in red blood cell survival and the severity of hemolysis in various
      anemias and allow more precise monitoring of the response to hydroxyurea, iron, r
      HuEPO, or other therapies.

PMID- 9260755
TI  - Gating strategy for immunophenotyping of leukemia and lymphoma.
AB  - Clinical specimens of blood, bone marrow, lymph node, extranodal tissue, and body
      fluid were collected from 67 cases of hematologic neoplasms (including chronic
      lymphoid leukemias, T- and B-cell lymphomas, and acute lymphoblastic and
      myelogenous leukemias) for comparison between the right-angle light scatter
      (RALS)/CD45 and the forward-angle light scatter (FALS)/RALS gating combinations.
      One to three diagnostic markers were selected from each case, yielding 124 paired
      results for comparison. We found that the percentage of tumor cell isolation and
      the total cell count in the tumor cell gate were higher in RALS/CD45 than in
      FALS/RALS. When 20% was used as a cutoff point, 30 markers in FALS/RALS failed to
      identify the tumor population, while only 3 markers in RALS/CD45 failed to do so.
      The discriminative factor in the RALS/CD45 gating was mainly the CD45 intensity,
      whereas all cases except 3 showed low RALS. Although T-cell neoplasms showed a
      higher proportion of high CD45 intensity, other groups shared similar ranges of
      CD45 intensity, which is therefore of limited value for differential diagnosis.
      The RALS/CD45 combination produces higher recovery and purity for tumor cell
      isolation than the FALS/RALS combination and should replace the latter for
      routine immunophenotyping of lymphoma and leukemia.

PMID- 9260757
TI  - Interphase cytogenetic (in situ hybridization) analysis of astrocytomas using
      archival, formalin-fixed, paraffin-embedded tissue and nonfluorescent light
      microscopy.
AB  - Astrocytomas contain nonrandom chromosomal abnormalities that recently have been
      correlated with shortened patient survival. Two frequently reported aberrations
      are trisomy 7 and monosomy 10. We assessed the numerical complement of
      chromosomes 7 and 10 in formalin-fixed, paraffin-embedded brain biopsy tissue
      from 28 diffuse astrocytomas by in situ hybridization using a nonfluorescent
      enzymatic detection system. Clinical follow-up of at least 5 years was available
      in 26 cases (93%). Monosomy 10 was identified in 7 cases (25%): astrocytoma, 1
      case; anaplastic astrocytoma, 1 case; and glioblastoma, 5 cases. Trisomy 7 was
      identified in 11 cases (39%): astrocytoma, 5 cases; glioblastoma, 6 cases.
      Multivariate analysis revealed that monosomy 10 was the most statistically
      significant negative predictor of patient survival. Numerical chromosomal
      abnormalities are detectable in astrocytomas in archival tissue using interphase
      cytogenetics and nonfluorescent light microscopy. Although larger studies are
      required, our data suggest that potentially useful prognostic information may be
      obtained with this approach.

PMID- 9260756
TI  - Value-based pathology: a cost-benefit analysis of the examination of routine and
      nonroutine tonsil and adenoid specimens.
AB  - To study the cost-effectiveness of the histologic examination of tonsil and
      adenoid specimens, the histologic diagnoses for all routine (2,700) and
      nonroutine (71) tonsil and adenoid specimens during a 10-year period were
      reviewed. There were 27 routine cases (1%) and 56 nonroutine cases (79%) with a
      diagnosis other than normal, tonsillitis, or hyperplasia. Twelve of the 27
      routine cases did not have a significant clinical history, and a potentially
      significant pathologic diagnosis was made in only 6 cases; in none of these cases
      did the pathologic diagnosis affect patient care. In all nonroutine cases, the
      pathologic diagnosis affected patient care. The average charge per case to detect
      potentially significant disease in routine and nonroutine cases was $64,718 and
      $525, respectively. We conclude that histologic examination of nonroutine cases
      is cost-effective, whereas in most routine cases with adequate clinical history,
      histologic examination is not cost-effective.

PMID- 9260758
TI  - Determinants of the autopsy decision: a statistical analysis.
AB  - Our goal was to use cross-sectional national mortality data to provide a
      multivariable statistical analysis of the factors that contribute to the decision
      of whether an autopsy will be performed. The identification of determinants of
      the autopsy is an important prerequisite for finding cost-effective alternatives
      for arresting or reversing the decline of autopsy rates in the circumstances in
      which the autopsy can continue to make a crucial contribution to clinical
      medicine and public health. The source of the data was 1986 National Center for
      Health Statistics (Washington, DC) mortality data tapes for Kentucky, Maryland,
      Minnesota, and Washington for the 1986 calendar year. Separate multiple logistic
      regressions were conducted on these data on a state-by-state basis, with a total
      of 139,063 individual mortality records as the unit of analysis. The dependent
      variable in all models was autopsy (yes/no). Odds ratios for selected explanatory
      variables were estimated for all four states, and the relative contribution of
      each explanatory variable was studied in a detailed analysis of one state. In
      general, the following independent variables had a statistically significant
      positive relationship with whether an autopsy will be performed: male sex;
      nonwhite ethnicity; death due to ill-defined or unknown cause; death due to
      accident, suicide, or homicide; presence of a nationally recognized medical
      center in the county of death; and death occurring in a standard metropolitan
      statistical area. In general, the following independent variables had a
      statistically significant negative relationship with whether an autopsy will be
      performed: older age at death; higher income level of the decedent; death in a
      nursing home; death at home; and residency in the county of death. The two most
      important variables influencing the autopsy decision were age at death
      (especially old age) and death due to accident, homicide, or suicide.

PMID- 9260759
TI  - Frequency of expression of prostate-specific antigen mRNA in lung tumors.
AB  - The presence of prostate-specific antigen (PSA) protein and messenger RNA (mRNA)
      was studied in 52 primary lung tumor tissues. The PSA protein was detected more
      frequently and at higher levels in lung tumor extracts from men. The levels of
      PSA protein in tumor extracts correlated with preoperative and postoperative
      serum PSA levels, suggesting a possible contamination of the tumor extracts with
      PSA from residual blood in the tumor vasculature. The PSA mRNA was detected by
      reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot
      hybridization in 24 (68%) of 35 tumors from men, in 9 (53%) of 17 tumors from
      women, and in 5 (71%) of 7 adjacent normal lung tissue specimens. The levels of
      PSA protein did not associate with patient age, the tumor stage, grade, or
      histologic type, or the nodal status. Similarly, PSA mRNA was not associated with
      any clinicopathologic variables, but squamous cell carcinomas, especially in men,
      were more frequently positive. A by-product of the RT-PCR procedure was cloned
      and sequenced and found to be a 450-base pair sequence not previously deposited
      in the data bank. We conclude that PSA mRNA and protein frequently can be
      detected in lung tumors and normal tissues from men and women but at levels much
      lower than those seen in breast carcinomas in women. The significance of the new
      450-base pair sequence remains to be determined.

PMID- 9260760
TI  - Histologic processing of microbiopsies from cervical smears is diagnostically
      useful in selected cases.
AB  - We analyzed the value in cervical cytology of a recently developed technique by
      which it is possible to remove thick tissue specimens, called microbiopsies, from
      cervical smears and to process them for histologic examination. In 12 (48%) of 25
      cervical smears in which microbiopsies were found, the histologic sections from
      them confirmed the cytologic diagnosis. Most cases involved classification of
      lesions diagnosed as cervical intraepithelial neoplasia. In 13 (52%) of 25
      smears, processing the microbiopsy allowed considerable modification of the
      cytologic diagnosis. In six of these cases, microbiopsies consisted of groups of
      columnar cells that were incorrectly classified as atypical on the basis of
      cytologic criteria. After histologic processing, the microbiopsies revealed
      nonatypical columnar cells in four cases and only mildly atypical columnar cells
      in two cases. In 3 of 13 smears, there were insufficient dispersed atypical cells
      for a conclusive diagnosis. Processing the microbiopsies in these cases allowed
      classification into one of the cervical intraepithelial neoplasia categories.

PMID- 9260761
TI  - Gonadoblastomas in 45,X/46,XY mosaicism: analysis of Y chromosome distribution by
      fluorescence in situ hybridization.
AB  - Gonadoblastomas are composed of nests of neoplastic germ cells and sex cord
      derivatives surrounded by ovarian-type stroma. These tumors are found almost
      exclusively in persons with gonadal dysgenesis associated with a Y chromosome or
      Y chromosome fragment, and accordingly, the Y chromosome has been implicated in
      gonadoblastoma oncogenesis. To evaluate this association, we used two-color
      fluorescence in situ hybridization with chromosome-specific probes to determine
      the distribution of the X and Y chromosomes in the tumor nests and surrounding
      stromal cells in paraffin tissue sections of three gonadoblastomas in two
      patients with gonadal dysgenesis and 45,X/46,XY mosaicism. Statistical analysis
      of the data from the fluorescence in situ hybridization demonstrated that in all
      three gonadoblastomas, the proportion of nuclei with a Y chromosome signal was
      significantly higher in the tumor cells than in the nontumoral cells of the
      surrounding stroma (P<.001). These results suggest that Y chromosome material
      participates in gonadoblastoma tumorigenesis.

PMID- 9260762
TI  - Immunologic response to Bartonella henselae as determined by enzyme immunoassay
      and Western blot analysis.
AB  - Bartonella henselae is now regarded as the etiologic agent of cat-scratch disease
      and a cause of bacillary angiomatosis. We examined the human immune response to
      Bartonella henselae infection using a newly developed enzyme immunoassay (EIA)
      and a Western blot procedure using outer-membrane proteins. The EIA showed 98.6%
      and 91.4% agreement with an indirect fluorescence method (IFA) for detection of
      IgM and IgG antibodies, respectively. By using Western blot analysis, reactivity
      to an 8-kd band showed significant correlation with positive results by the IgM
      IFA and EIA. In contrast, reactivity to 209-, 208.5-, 208-, 116-, and 80-kd bands
      was identified only in positive IgG IFA serum samples. The EIA and Western blot
      should be useful tests in determining the antibody response to B. henselae
      infection and may also be important in determining the critical epitopes in the
      host-parasite interaction of this organism.

PMID- 9260763
TI  - Infections with Roseomonas gilardii and review of characteristics used for
      biochemical identification and molecular typing.
AB  - Roseomonas is a recently described genus of gram-negative coccobacilli formerly
      designated as "pink-coccoid" groups I through IV by the Centers for Disease
      Control and Prevention (Atlanta, Ga) because of the organism's characteristic
      pink colonies. Since 1991 we have isolated Roseomonas from eight patients; in
      seven from blood cultures and in one from a skin lesion. The seven blood isolates
      were from patients with clinically significant underlying diseases who had
      central venous catheters in place; the majority were associated with
      polymicrobial catheter infections. Additional characteristics of their infections
      are described. The eight isolates had originally been identified by us as Centers
      for Disease Control (CDC) pink-coccoid group III. These organisms were re
      identified using the criteria of Rihs et al, and all isolates fit most closely
      with Roseomonas gilardii. Antibiotic profiles were fairly homogeneous showing
      susceptibility to many antibiotics, but uniform resistance to cefoxitin,
      ceftazidime, and piperacillin. Attempts to determine whether the isolates were
      the same strain by pulsed-field gel electrophoresis suggested that 3 of the
      isolates were similar. Random amplified polymorphic DNA analysis, however,
      demonstrated that each of the eight isolates was a unique strain.

PMID- 9260764
TI  - Cerebrospinal fluid broth culture isolates: their significance for antibiotic
      treatment.
AB  - Enriched broth medium is routinely used as a supplement for agar plate culture of
      cerebrospinal fluid (CSF). To assess the clinical utility of broth cultures, 151
      consecutive CSF bacterial and fungal isolates obtained from 91 patients were
      retrospectively reviewed for the effect of results on treatment. Treatment
      decisions associated with individual CSF specimens for which isolates were
      recovered from thioglycollate broth only were compared with the treatment
      decisions associated with CSF specimens for which isolates were recovered by agar
      plate culture. Treatment was defined as initiation of or change in antimicrobial
      therapy based on the reporting of CSF culture isolates. Thirty-six (24%) of the
      151 isolates were recovered in broth only. Three (8%) of these 36 isolates (from
      34 patients) resulted in treatment with antimicrobial agents; however, 2 of the 3
      treated isolates (Candida tropicalis, Proteus mirabilis) were recovered from a
      second CSF specimen in agar plate culture within 24 hours. Thus, only a single
      isolate (3%; Staphylococcus epidermidis) was treated based solely on a positive
      broth culture result. In contrast, 60 (52%) of the 115 isolates recovered in agar
      plate culture from 23 (40%) of 57 patients were treated (staphylococci, 28; gram
      negative bacilli, 14; Cryptococcus neoformans, 10; Streptococcus pneumoniae, 3;
      Streptococcus sanguis, 1; other, 4). We conclude that treatment with
      antimicrobial agents based on isolates recovered from CSF specimens in broth
      culture alone is infrequent and infer from the data that the use of CSF broth
      cultures contributes little to treatment decisions.

PMID- 9260765
TI  - Fine-needle aspiration biopsy of mesenchymal lesions: the value of
      clinicoradiologic correlation and the importance of histogenetic subtyping.

PMID- 9260766
TI  - The diagnostic laboratory as clinical consultant: public health implications.

PMID- 9260767
TI  - Adrenocorticotropic hormone-independent adrenocortical hyperplasia and ACTH
      independent bilateral adrenocortical macronodular hyperplasia.

PMID- 9260768
TI  - Type V hyperlipidemia associated with diabetic ketoacidosis.

PMID- 9260770
TI  - The mechanism of respiratory rhythm generation during constant flow assisted
      mechanical ventilation in the decerebrated dog.
AB  - In awake human subjects input from the forebrain has significant effects on the
      respiratory pattern during assisted (AMV) and controlled (CMV) mechanical
      ventilation. The hypothesis in this animal study was that if the influence from
      the forebrain is eliminated, the respiration during AMV and that during CMV is
      controlled by the same mechanism. Fifteen decerebrated and tracheostomized dogs
      were subjected to CMV with a variety of combinations of tidal volume and
      frequency. The respiratory rhythm during CMV was simulated by a mathematical
      model composed of the central respiratory activity and inputs from pulmonary
      receptors. During AMV, the respiratory cycle duration was prolonged, and this was
      found to be the summated effect of prolonged Ttg (ventilator trigger period) and
      shortened Tinf (lung inflation period). When these changes in Ttg and Tinf were
      included, the model for CMV predicted respiratory changes during AMV. We
      concluded that the basic mechanism controlling AMV and CMV may be the same.

PMID- 9260769
TI  - Adrenocorticotropin-independent macronodular adrenocortical hyperplasia
      associated with multiple colon adenomas/carcinomas which showed a point mutation
      in the APC gene.
AB  - We report a male Japanese with corticotropin (ACTH)-independent macronodular
      adrenocortical hyperplasia (AIMAH) associated with multiple colon
      adenomas/carcinomas. The plasma cortisol level was elevated with no diurnal
      rhythm and was not suppressed with dexamethasone. Basal plasma ACTH was
      unmeasurable but subnormally increased after administration of metyrapone or
      corticotropin releasing hormone. Both adrenals were resected and weighed 90g; the
      histopathologic findings were similar to those of AIMAH as previously reported.
      At least 21 colon lesions which were adenomas or carcinomas, were resected
      endoscopically or surgically. This is the second reported case of the association
      of AIMAH with multiple colon polyps. An APC gene point mutation was detected in
      the colon cancer tissue by polymerase chain reaction (PCR)-single strand
      conformation polymorphism (SSCP)/direct sequencing analysis at the putative
      splice acceptor site consensus sequence. However, no abnormality of APC gene was
      detected in the adrenocortical hyperplastic tissue. The possible etiological
      coexistence of these two diseases is discussed.

PMID- 9260771
TI  - Pain-related and electrically stimulated somatosensory evoked potentials in
      patients with Machado-Joseph disease and multiple system atrophy.
AB  - We investigated the ascending somatosensory pathway for pain in 8 patients with
      Machado-Joseph disease (MJD) and multiple system atrophy (MSA). Pain-related
      somatosensory evoked potentials (pain SEPs) by CO2 laser stimulation were
      examined together with conventional electrically stimulated somatosensory evoked
      potentials (electric SEPs). The sporadic cerebellar ataxia of patients with MSA
      showed a normal pattern of pain SEPs as well as electric SEPs. However, pain and
      electric SEPs were abnormal for the central and/or peripheral ascending pathway
      in MJD. These abnormalities of pain and electric SEPs in MJD were not related to
      the clinical severity of sensory impairment, but they indicate that MJD presents
      a subclinical abnormality for the ascending somatosensory pathways not only for
      vibratory sense but also for pain sense.

PMID- 9260772
TI  - Malignant lymphoma originating in the jejunum of a long-term follow-up case of
      protein-losing enteropathy.
AB  - A 50-year-old female patient, who had been followed for 15 years for protein
      losing enteropathy, was hospitalized due to epigastric pain. Examination on
      admission revealed that the patient was in the sub-ileus state. On the 26th day
      after admission, she complained of severe abdominal pain and shortly after she
      went into shock. The emergency laparotomy documented intestinal perforation and a
      tumor. The perforated site was right at the middle of tumor. The histological and
      histochemical studies identified the tumor as malignant lymphoma of B lymphocyte
      lineage. As far as we know, this is the third case of malignant lymphoma
      occurring in the jejunum in a patient with protein-losing enteropathy in Japan.
      The possible relationship between lymphomas and protein-losing enteropathy is
      discussed.

PMID- 9260773
TI  - Sclerosing cholangitis associated with hypereosinophilic syndrome.
AB  - A 15-year-old male with hypereosinophilic syndrome was admitted to our hospital
      because of general malaise and abnormal liver function tests. Endoscopic
      retrograde cholangiopancreatography demonstrated bile duct changes consistent
      with primary sclerosing cholangitis. The patient's liver profile tests returned
      to normal after treatment with prednisolone and ursodeoxycholic acid. In this
      case, eosinophils might have played an important role in the pathogenesis of the
      bile duct lesion.

PMID- 9260774
TI  - An adult case of Cockayne syndrome without sclerotic angiopathy.
AB  - We report an autopsy case of Cockayne syndrome (CS). A 40-year-old Japanese woman
      was admitted to our hospital for cachexia. She had displayed the striking
      features of CS, including dwarfism, mental retardation, neural deafness, ataxia,
      intracranial calcifications, and progeria since her childhood. Endocrinological
      examinations suggested normal pituitary function and a disorder of the
      hypothalamus or the cerebrum. She died of acute pneumonia at the age of 42.
      Autopsy findings showed typical abnormalities in the central nervous system
      compatible with CS; however, no atherosclerotic change was observed in the
      systemic arteries.

PMID- 9260775
TI  - Diabetic lipemia with maturity-onset diabetes of the young.
AB  - A 19-year-old woman with diabetic lipemia and maturity-onset diabetes of the
      young (MODY) is reported. Though her insulin secretory activity was preserved,
      she fell into mild diabetic ketoacidosis (DKA) and showed type V hyperlipidemia.
      Post-heparin plasma activity of lipoprotein lipase (LPL) was decreased even 10
      days after initiating insulin injection but not deficient. The abnormalities in
      lipid metabolism were improved by long-term insulin treatment. Though the
      contribution of the genetic background to the lipid abnormalities is not clear,
      the characteristics of MODY in this patient including insulin secretory capacity
      under stress conditions such as DKA might play a role in the development of
      diabetic lipemia.

PMID- 9260776
TI  - Immediate-type human insulin allergy successfully treated by continuous
      subcutaneous insulin infusion.
AB  - A 63-year-old insulin-dependent diabetic woman was hospitalized with itchy skin
      wheals at the injection sites of human insulin. After intradermal skin testing
      was performed, the erythema and wheal was recorded immediately. The increased
      titer of human insulin-specific IgE antibody indicated immediate-type allergy
      against human insulin. Administration of an anti-allergic drug or desensitization
      for human insulin every 2 hours was not effective. After continuous subcutaneous
      insulin infusion (CSII) therapy was performed, both the itching and wheal
      disappeared. The process may be a desensitization through CSII. CSII may be
      useful in the treatment for human insulin allergy.

PMID- 9260777
TI  - Postprandial atrioventricular block in a patient with diabetes mellitus.
AB  - Postprandial atrioventricular (AV) block and hypotension occurred in an 80-year
      old man with a 13-year history of diabetes mellitus. Two weeks before admission,
      he experienced syncope on two occasions after lunch. Master's two-step test
      induced second degree AV block (2:1 block). Four days after admission, syncope
      recurred while walking 1 hour after eating; electrocardiogram (ECG) showed
      complete AV block following 2:1 block. PP interval analysis suggested phase 3
      block as the mechanism of AV block. Electrophysiologic study revealed 2:1 HV
      block. Postprandial syncope ceased after permanent pacemaker implantation.
      Postprandial AV block and hypotension merit close attention in diabetics.

PMID- 9260778
TI  - Three cases of Gitelman's syndrome possibly caused by different mutations in the
      thiazide-sensitive Na-Cl cotransporter.
AB  - Three adult Japanese cases of Gitelman's syndrome were characterized by secondary
      aldosteronism, hypokalemic alkalosis, hypomagnesemia, and hypocalciuria. Two were
      revealed to be familial cases. A mutation in the thiazide-sensitive Na-Cl
      cotransporter gene, which had already been confirmed in one family (Takeuchi et
      al. J Clin Endocrinol Metab 81: 4496,1996), was not detected in the other two
      cases. These observations may possibly support the previous report (Simon et al.
      Nature Genet 12: 24, 1996) that Gitelman's syndrome is caused by a variety of
      mutations in the thiazide-sensitive Na-Cl cotransporter.

PMID- 9260779
TI  - Xanthogranulomatous pyelonephritis.
AB  - A 76-year-old woman presented with spiking fever and right back pain.
      Ultrasonography (US) revealed that her right kidney was enlarged. Computed
      tomography (CT) showed the parenchyma was replaced by non-enhancing masses but
      the overall kidney shape was maintained. These findings were compatible with
      those of xanthogranulomatous pyelonephritis (XP). The nonenhancing masses on CT
      coincided with the multiple butter yellow nodules of the resected kidney and
      microscopically these lesions were proved to be abscesses with xanthoma cells. In
      this case, the US and CT findings reflected the pathological feature of XP and
      thus these techniques are thought to be useful for the diagnosis of XP.

PMID- 9260780
TI  - Brain metastasis in malignant pleural mesothelioma.
AB  - A 55-year-old male who had a remote history of occupational asbestos exposure
      consulted us because of chest pain. Chest X-ray revealed diffuse pleural
      thickening and pleural effusion on the right. A diagnosis of malignant
      mesothelioma, biphasic type was made by needle pleural biopsy. Fourteen months
      later, the patient died of brain metastasis. At autopsy, malignant mesothelioma
      of the pleura with metastasis to the brain and bilateral adrenal glands was
      observed. Brain metastases proven by autopsy are rare in cases of malignant
      mesothelioma. The ferruginous body count in the lung tissue was 16 per gram of
      wet weight.

PMID- 9260781
TI  - Acute myeloid leukemia accompanied by multiple thrombophlebitis.
AB  - A 66-year-old woman suffering from fever and thrombophlebitis was referred to our
      hospital. A peripheral blood examination revealed hyperleukocytosis with 96%
      blast cells and thrombocytopenia. The patient was diagnosed as having acute
      myeloid leukemia (AML) accompanied by disseminated intravascular coagulation
      (DIC). A marked decrease in protein C (PC) antigen and activity were observed. In
      this case, PC levels were lower than those observed in AML with DIC. Induction
      therapy for leukemia and treatment of DIC were started on the first day of
      hospitalization. The patient achieved complete remission, with PC antigen and
      activity levels normalized.

PMID- 9260782
TI  - Testing for Helicobacter pylori infection after antibiotic treatment.

PMID- 9260783
TI  - On making the diagnosis of ulcerative colitis.

PMID- 9260784
TI  - Celiac disease, an eminently treatable condition, may be underdiagnosed in the
      United States.

PMID- 9260785
TI  - Guilty as charged: bugs and drugs in gastric ulcer.
AB  - Gastric ulcer disease remains a cause of hemorrhage, perforation, outlet
      obstruction, and death. Recent advances in the understanding of peptic ulcer
      disease indicate that infection with Helicobacter pylori and ingestion of
      nonsteroidal anti-inflammatory drugs (NSAIDs) are the cause of almost all gastric
      and duodenal ulcers. Our therapy, therefore, is in a state of transition: the old
      acid-suppressive temporary therapy that allows frequent ulcer recurrences and
      complications is being replaced by curative therapies. The old therapy, by
      reducing gastric acid secretion or enhancing gastric mucosal defenses, inhibited
      the cofactors needed for ulcer development. Acid suppression relieved symptoms
      and healed ulcers, while defense enhancers, such as prostaglandin analogs healed
      and prevented acute NSAID-induced gastric ulcers. These benefits were maintained,
      however, only as long as acid-reducing agents or mucosal defense enhancers were
      continued. On the other hand, curative therapies (such as eradicating H. pylori
      infection and/or stopping the use of NSAIDs) eliminate the causes of ulcer.
      Curative combination regimens consisting of antibiotics, ranitidine bismuth
      citrate, bismuth, and proton pump inhibitors have been approved by the Food and
      Drug Administration. These new regimens can cure benign gastric ulcer.
      Unfortunately, we cannot always determine which gastric ulcers are benign, and
      concern about gastric cancer remains. All gastric ulcers therefore still require
      biopsy and histological examination. With new treatment regimens, the time may be
      rapidly approaching when ulcer disease will be "history."

PMID- 9260786
TI  - A review of the management of post-cholecystectomy biliary leaks during the
      laparoscopic era.

PMID- 9260787
TI  - Accuracy of invasive and noninvasive tests to diagnose Helicobacter pylori
      infection after antibiotic treatment.
AB  - OBJECTIVES: To compare the diagnostic accuracy of the most widely available tests
      for diagnosis of Helicobacter pylori infection after antibiotic treatment.
      METHODS: A total of 59 H. pylori-positive, duodenal ulcer patients (mean age,
      40.7 +/- 11.7 yr; 40 male and 19 female) were treated for 2 wk with either
      amoxicillin-metronidazole (n = 36) or omeprazole-amoxicillin-tinidazole (n = 23),
      and after 4 wk, were tested for H. pylori infection by [14C]urea breath test
      (UBT), serum IgG antibody level, and multiple antral biopsies for rapid urease
      testing, histology, Warthin-Starry stain, and polymerase chain reaction to detect
      H. pylori DNA. Infection status was established by a concordance of test results.
      RESULTS: H. pylori was eradicated in 47 patients (80%). UBT and rapid urease
      testing had the best sensitivity and specificity, although not statistically
      different to Warthin-Starry stain and polymerase chain reaction. Serology and
      histology had little diagnostic value in this setting due to high proportion of
      false-positive results. CONCLUSIONS: Noninvasive UBT is as accurate in predicting
      H. pylori status after antibiotic treatment as rapid urease testing and Warthin
      Starry stain. Especially for duodenal ulcer patients, UBT could be considered the
      gold standard to confirm eradication of H. pylori.

PMID- 9260788
TI  - Patchy cecal inflammation associated with distal ulcerative colitis: a
      prospective endoscopic study.
AB  - OBJECTIVES: It is generally believed that the mucosal inflammation in ulcerative
      colitis is characterized by a diffuse, continuous involvement starting from the
      rectum without "skip areas." It was the aim of this study to examine 20 patients
      with established "left-sided ulcerative colitis" prospectively by ileocolonoscopy
      with biopsies to determine the extent and the continuity of the mucosal
      inflammation and the incidence of skip lesions in ulcerative colitis. METHODS:
      Twenty patients with left-sided ulcerative colitis underwent a complete
      ileocolonoscopy with biopsies of the terminal ileum and all colonic segments. The
      patients remained in clinical follow-up for at least 8 yr after the initial
      examination. RESULTS: The upper margin of inflammation was sharply demarcated in
      6 patients and gradual in 14. Segmental inflammation, separated from the distal
      inflamed segment by apparently uninvolved mucosa, was found in 15 patients (75%)
      and always included the area around the appendiceal orifice. The correlation
      between endoscopic abnormalities and histological changes was excellent.
      CONCLUSION: In so-called "left-sided" ulcerative colitis distal involvement may
      be accompanied by more proximal areas of inflammation, particularly in the
      periappendiceal area of the cecum.

PMID- 9260789
TI  - Celiac disease in an adult population with insulin-dependent diabetes mellitus:
      use of endomysial antibody testing.
AB  - OBJECTIVE: Studies from Europe and North Africa suggest an association between
      type 1 diabetes mellitus (IDDM) and celiac disease (CD). Although IDDM is as
      common in the United States as it is in Europe, CD is diagnosed much less often
      in this country than in Europe. The purpose of our study was to determine the
      frequency with which CD occurs in patients with IDDM in the United States.
      METHODS: Several serological tests are used for CD screening. The most specific
      and sensitive of these, the antiendomysial antibody, is the indirect
      immunofluorescence test which uses monkey esophagus smooth muscle as substrate.
      This test, which correlates closely with actual enteropathy, was used to screen
      185 unselected patients with IDDM who attended the Diabetic Clinic or were housed
      on the Diabetic Unit of the University of Iowa Hospitals and Clinics. RESULTS:
      Nine of 185 patients had positive IgA antiendomysial antibody tests. Antibody
      positivity did not correlate with the presence of diabetic complications, age,
      sex, or duration of IDDM. Five of nine antibody-positive patients underwent
      subsequent small intestinal biopsy. Enteropathy was confirmed in four of these
      patients. CONCLUSIONS: These data suggest that CD is more common in American
      patients with IDDM than was previously suspected.

PMID- 9260790
TI  - The risk of cancer and dysplasia among ulcerative colitis patients with primary
      sclerosing cholangitis.
AB  - BACKGROUND: Ulcerative colitis (UC) patients with primary sclerosing cholangitis
      (PSC) may have an increased risk for colonic dysplasia or cancer. They also may
      have higher levels of carcinogenic secondary bile acids and, thus, be more likely
      to develop cancer in the right side of the colon, where secondary bile acid
      concentrations are highest. METHODS: Since 1983, 1212 UC patients have undergone
      total proctocolectomy with ileal pouch-anal anastomosis at the Cleveland Clinic.
      All 27 patients with PSC were compared with the remaining 1185 patients in a
      historical cohort study. RESULTS: Dysplasia detected during cancer surveillance
      was the indication for surgery in 16 (59.5%) PSC patients and 136 (11.5%)
      controls [adjusted relative risk (RR), 6.9; 95% confidence interval (CI), 3.0
      16.0]. Dysplasia or cancer was found in the resected specimen in 18 (66.7%) PSC
      patients and 145 (12.2%) controls (RR 10.4, CI 4.1-26.1). Right-sided cancers
      (proximal to the splenic flexure) were found in all four PSC patients with cancer
      and in 20 of 49 controls with cancer (RR 2.5, CI 1.3-5.4). CONCLUSIONS: UC
      patients with PSC are at a significantly increased risk for dysplasia or cancer.
      The high proportion of right-sided cancers supports the contention that secondary
      bile acids are carcinogenic and increase the likelihood of cancer in the proximal
      colon.

PMID- 9260791
TI  - Features associated with painless peptic ulcer bleeding.
AB  - BACKGROUND: Painless peptic ulcer bleeding is well recognized, although clinical
      features associated with the absence of abdominal pain have received little
      attention. METHODS: Patients admitted for upper GI bleeding at a large inner-city
      hospital were questioned prospectively at the time of initial evaluation
      regarding the presence of any dyspepsia and/or abdominal pain, including
      nocturnal symptoms, within 1 wk of admission. A number of other clinical and
      endoscopic features were also recorded. The cause of upper GI bleeding was
      determined in most patients by endoscopy. Patients were excluded if a reliable
      history could not be obtained or if the ulcer was malignant. RESULTS: Over the 50
      month study period, 449 patients with upper GI bleeding caused by peptic ulcer
      were evaluated, including 236 with gastric ulcer (53 prepyloric) and 213 with
      duodenal ulcer (28 with channel ulcer). Of these patients, abdominal pain was
      absent in 191 (43%; 95% confidence interval, 38-47%). There appeared to be no
      relationship of pain to race, gender, alcohol use, ulcer location, use and
      duration of nonsteroidal anti-inflammatory drugs, history of ulcer, or
      comorbidity. The only statistically significant correlates with abdominal pain
      were ulcer size (77% of patients with ulcers >2 cm reported pain as compared with
      49% of patients with ulcers <1 cm; p < 0.001), tobacco use (p = 0.041), and age
      <80 yr (p = 0.02). CONCLUSIONS: Approximately half the patients with a bleeding
      peptic ulcer have no abdominal pain. Large ulcer size, use of tobacco, and age
      <80 yr seem to be the main determinants of ulcer-related pain in this setting.

PMID- 9260792
TI  - Risk factors for Barrett's esophagus in community-based practice. GORGE
      consortium. Gastroenterology Outcomes Research Group in Endoscopy.
AB  - OBJECTIVES: Endoscopy is often performed in patients with gastroesophageal reflux
      (GER) disease because of concern about the presence of Barrett's esophagus (BE).
      The purpose of this study was to determine whether the duration of GER symptoms
      and/or a history of esophagitis was associated with an increased risk of BE.
      METHODS: This was an observational, prospective, community-based study.
      Consecutive patients undergoing elective endoscopy because of GER symptoms were
      enrolled. Endoscopy reports and pathological findings were reviewed to classify
      patients as having no esophagitis, esophagitis, or probable BE. Correlations with
      duration of symptoms and a history of esophagitis were analyzed. RESULTS: In all,
      701 of 2641 patients (27%) undergoing elective endoscopy had GER symptoms, and 77
      of these patients had probable BE. Compared with patients with GER symptoms for
      less than 1 yr, the odds ratio for BE in patients with GER symptoms for 1-5 years
      was 3.0 and increased to 6.4 in patients with symptoms for more than 10 yr (p <
      0.001). A history of esophagitis was not an independent risk factor for BE (p =
      0.17). CONCLUSIONS: Prevalence of BE is strongly associated with duration of GER
      symptoms.

PMID- 9260793
TI  - Iron overload in patients with chronic viral hepatitis: how common is it?
AB  - OBJECTIVES: To establish the prevalence of increased hepatic iron content in
      patients with hepatitis C virus-related chronic hepatitis and to assess the
      accuracy of serum iron and ferritin in detecting tissue iron overload. METHODS:
      Serum iron, serum ferritin, and hepatic iron content were determined in 81
      consecutive patients undergoing liver biopsy for chronic ALT elevation and
      hepatitis C virus infection. Moreover, in a subgroup of 28 patients, outcome of a
      6-month course of interferon (IFN) treatment (6 million U of recombinant IFN,
      three times weekly) was determined after a mean follow-up of 24 +/- 6 months and
      the outcome was compared with the pretreatment values of hepatic iron content.
      RESULTS: Elevated serum iron or ferritin levels were detected in approximately
      40% of patients, but elevated hepatic iron content was observed in only eight
      patients (10%). One of these patients had a hepatic iron index > 1.9, indicating
      hemochromatosis. Liver iron content and serum iron levels were not correlated. No
      differences in hepatic iron content were observed among patients with a sustained
      response to IFN (seven patients), short-term responders (seven patients), or
      nonresponders (14 patients). CONCLUSIONS: Ten percent of patients with chronic
      hepatitis C have elevated hepatic iron content. These patients cannot be
      identified using serum markers of iron status. The relationship between liver
      iron and response to IFN treatment requires further prospective investigations.

PMID- 9260794
TI  - Utility of a discriminant score for diagnosing advanced fibrosis or cirrhosis in
      patients with chronic hepatitis C virus infection.
AB  - OBJECTIVE: The aim of the study was to assess the utility of a modified three
      parameter cirrhosis discriminant score (CDS) for diagnosing advanced fibrosis or
      cirrhosis in patients with evidence of chronic hepatitis C. METHODS: We examined
      liver tissue from 79 patients. Patients with a histological fibrosis score of 0-2
      made up group A, and patients with a score of 3 or 4 (advanced fibrosis or
      cirrhosis) group B. RESULTS: The modified CDS (possible total score 0-11) was
      derived from three laboratory parameters: platelets, ALT/AST ratio, and PT. The
      total score was significantly lower in group A (4.3 +/- 2.0) than in group B (7.9
      +/- 1.4) (p < 0.0001). There was a positive correlation between the CDS and
      histological fibrosis score (r = 0.64,p < 0.0001). With 8 or above as the cutoff
      value, the CDS had a sensitivity of 46% and a specificity of 98% for the
      diagnosis of histological fibrosis scores of 3 or 4. CONCLUSIONS: We conclude
      that a three-parameter CDS is useful for identifying patients with hepatitis C
      and a high likelihood of cirrhosis. Patients with a CDS < or =7 still require
      histological examination to identify advanced fibrosis or cirrhosis.

PMID- 9260795
TI  - Serial quantitation of serum core protein and viral RNA of hepatitis C virus
      after interferon therapy: increase in viral loads in biochemical responders.
AB  - OBJECTIVES: Interferon (IFN) therapy is often ineffective in eradicating
      hepatitis C virus (HCV). Some patients show normal serum ALT levels for a long
      time after IFN therapy despite the presence of HCV. These patients are considered
      not virological responders but biochemical responders. We investigated the
      changes in the amount of HCV after IFN therapy in biochemical responders.
      METHODS: Nine biochemical responders and 11 nonresponders were studied. Serum HCV
      amount was measured by fluorescence enzyme immunoassay for HCV core (pg/ml) and
      Amplicor HCV Monitor test for HCV RNA (logarithms of copy numbers per
      milliliter). RESULTS: In biochemical responders, core protein and HCV RNA were
      increased significantly at 1 month after IFN therapy (291 +/- 191 pg/ml and 5.4
      +/- 0.9, respectively; p < 0.05 for both) and at 1 yr (324 +/- 189 pg/ml and 5.6
      +/- 0.7, respectively; p < 0.01 for both) compared with pretreatment values (122
      +/- 114 pg/ml and 4.8 +/- 0.9, respectively). The change ratios of core protein
      at 1 month and 6 months after therapy to the pretreatment values were
      significantly higher in biochemical responders (3.2 +/- 2.4 and 2.9 +/- 2.3,
      respectively) than in nonresponders (0.9 +/- 0.7 and 1.1 +/- 0.8, respectively)
      (p < 0.05 for both). Similarly, the change ratios of HCV RNA at 1 month and 1 yr
      after IFN therapy were significantly higher in biochemical responders (9.9 +/-
      14.6 and 12.8 +/- 15.1) than in nonresponders (0.6 +/- 0.5 and 1.2 +/- 1.2) (p <
      0.05 for both). CONCLUSIONS: HCV amount increased significantly after IFN therapy
      in biochemical responders, whereas it did not change notably in nonresponders.

PMID- 9260796
TI  - Prospective, multivariate evaluation of CLOtest performance.
AB  - OBJECTIVES: To determine prospectively the effect of aspirin, nonsteroidal anti
      inflammatory drugs, H2-receptor antagonists, proton pump inhibitors, alcohol
      intake, race, age, history of Helicobacter pylori eradication attempts, and
      gastric biopsy location on CLOtest performance. METHODS: Biopsy specimens were
      obtained from the antrum, greater curve, and proximal stomach. One biopsy
      specimen from each site (except for the proximal stomach) was used for the
      CLOtest and two or more specimens were used for histopathology. Giemsa staining
      was used for the definitive determination of H. pylori status. RESULTS: One
      hundred seventeen patients were included in the study, and 50 of these were
      infected with H. pylori. The sensitivity and specificity of an antral CLOtest,
      based on the results of Giemsa-stained sections from the antrum alone, were 72.7
      and 98.6%, respectively, whereas they were 66.0 and 100% when based on the
      results of Giemsa-stained sections from all three gastric biopsy sites. The
      sensitivity and specificity of a body CLOtest, based on the results of Giemsa
      stained sections from the body alone, were 80.5% and 93.4%, whereas they were
      76.0% and 100% when based on the results of Giemsa-stained sections from all
      three gastric biopsy sites. Combining CLOtest results from the antrum and body
      increased CLOtest sensitivity to 82.0%. Univariate analysis revealed only one
      factor significantly associated with CLOtest concordance: absence of alcohol
      consumption (p < 0.02). Stepwise logistic regression demonstrated that absence of
      alcohol use again was independently associated with the concordance between
      overall CLOtest and all Giemsa-stained biopsy specimen results (p < 0.03) as well
      as between body CLOtest and body Giemsa-stained biopsy specimen results (p <
      0.03). Additional independent and significant associations were noted between
      antral CLOtest-antral Giemsa-stained biopsy specimen results and no history of H.
      pylori eradication attempts (p = 0.04) and between body CLOtest-body Giemsa
      stained biopsy specimen results and race (African-American) (p < 0.03).
      CONCLUSIONS: Obtaining a gastric biopsy specimen from the antrum as well as from
      the body increased CLOtest detection of H. pylori. CLOtest performance was shown
      to be affected by several demographic and clinical factors.

PMID- 9260797
TI  - Genetic analysis of the cytotoxin-associated gene and the vacuolating toxin gene
      in Helicobacter pylori strains isolated from Taiwanese patients.
AB  - OBJECTIVE: Two virulence factors encoded by the cytotoxin-associated (cagA) gene
      and the vacuolating toxin (vacA) gene of Helicobacter pylori are known to be
      associated with gastroduodenal pathologic conditions. In this report, nucleotide
      sequence of cagA and vacA and the serum antibody response to the CagA antigen in
      H. pylori isolates from Taiwanese patients were studied. METHOD: cagA and vacA
      were characterized in 173 H. pylori strains by polymerase chain reaction and DNA
      hybridization analyses. The presence of serum IgG antibodies against CagA was
      assessed by Helico-blot Western blot system. Sequence analysis of polymerase
      chain reaction-amplified vacA and cagA was performed for two strains. RESULTS:
      cagA was detected in all the isolates with peptic ulcers and gastric cancer. Of
      54 strains with non-ulcer dyspepsia, 51 were found to be cagA+. Serum antibodies
      to CagA were detected for 99.2% of cagA+ strains compared with 0% of strains
      lacking cagA. vacA was detected in all isolates. Sequence analysis of vacA and
      cagA indicated that sequences of two Taiwanese strains were closely related to
      each other (95.9% and 97% nucleotide identity, respectively) but less homologous
      to the published strains (90.9% and 91.4% mean nucleotide sequence identity,
      respectively). CONCLUSIONS: The strong association (98%) of cagA+ strains with
      Taiwanese patients suggests that the cagA+ phenotype could not be used as a
      single marker of high-risk patients in Taiwan. Moreover, sequence analysis
      indicates that Taiwanese strains contain different genetic sequences from those
      in other geographic regions.

PMID- 9260798
TI  - Primary amino-bisphosphonates: a new class of gastrotoxic drugs--comparison of
      alendronate and aspirin.
AB  - BACKGROUND: Alendronate and pamidronate are primary amino-bisphosphonates used in
      the treatment of metabolic bone disease. Both drugs have been associated with
      reversible erosive esophagitis and as a result pamidronate is approved in the
      United States only for parenteral use. In rats, alendronate causes acute gastric
      mucosal damage similar to that seen with aspirin or nonsteroidal anti
      inflammatory drugs. METHODS: We performed a blinded, crossover, randomized,
      single-center, placebo-controlled, endoscopic comparison of alendronate (40
      mg/day), aspirin (1, 300 mg/day), and placebo to evaluate the presence and degree
      of mucosal damage to the esophagus, stomach, and duodenal bulb. RESULTS: Twelve
      normal healthy volunteers were studied both before and after 4 days of drug
      therapy. Placebo caused no visible endoscopic damage. In contrast, both aspirin
      and alendronate were associated with visible gastric mucosal injury in the
      majority of those studied (75 and 58%, respectively) and both were significantly
      greater than placebo (p < 0.001). The gastric mucosal injury was deemed severe in
      50% of those receiving alendronate or aspirin; one alendronate-associated gastric
      ulcer was seen. Esophageal and duodenal bulb injury was seen once each, and both
      were associated with alendronate. CONCLUSIONS: The primary amino-bisphosphonate
      alendronate causes mucosal injury to the upper gastrointestinal tract similar to
      aspirin. Even when used according to manufacturer's dosing instructions
      alendronate should probably be used with caution.

PMID- 9260799
TI  - Gluten sensitivity in the rectal mucosa of first-degree relatives of celiac
      disease patients.
AB  - BACKGROUND/AIMS: Rectal gluten challenge is a simple, sensitive, and specific
      test of mucosal gluten sensitivity. Our aims in this study were to evaluate
      gluten sensitivity in a group of relatives of celiac patients and to compare
      these findings with those obtained on small bowel histology, celiac disease
      related serology, and HLA typing. METHODS: A 4-h rectal gluten challenge was
      performed with 6 g of crude gluten in saline solution in 29 first-degree
      relatives, 20 well-diagnosed celiac patients, and 10 subjects in whom celiac
      disease had been excluded. The number of intraepithelial lymphocytes in pre- and
      postchallenge frozen rectal biopsies (pan T-cell immunocytochemistry) was
      quantified by computerized image analysis. RESULTS: The intraepithelial
      lymphocyte response after gluten instillation was significantly higher in celiac
      disease patients (median, 126% increase above the baseline count; 95% confidence
      interval: 61-213%) compared with control subjects (median, -5%; 95% confidence
      interval: -29-5%). Using a cut-off of 20% change in intraepithelial lymphocyte
      count, 14 relatives (48%) showed a celiac-like response. Two of these subjects
      had partial villous atrophy and increased lymphocyte counts in the small bowel
      mucosa. One of them also exhibited a positive celiac disease-related serology and
      the typical celiac human lymphocyte antibody (HLA) DQ2. The remaining 12, and all
      those relatives with a negative challenge, had normal small bowel mucosa and were
      negative for antigliadin and endomysial antibodies. The characteristic celiac HLA
      (DQA1 0501 DQB1 0201 heterodimer) was identified in five relatives with positive
      challenge (including the patient with more severe mucosal atrophy) but was also
      present in eight relatives with no evidence of gluten sensitivity in the rectal
      mucosa. CONCLUSIONS: Our study characterizes a subgroup of relatives of celiac
      patients who show mucosal evidence of sensitization after local instillation of
      gluten in the rectum but who have no other features of celiac disease.

PMID- 9260800
TI  - Bone mineralization and body composition in young patients with celiac disease.
AB  - OBJECTIVES: The aim of the study was to establish whether body composition in
      patients with celiac disease is normal and influenced by the age at diagnosis or
      by the duration of the gluten free diet. METHODS: A group of 66 children with
      celiac disease and 76 healthy controls were studied by dual energy x-ray
      absorptiometry. We compared celiac patients with the control group, and within
      the celiac disease group, we compared patients with different age at diagnosis
      (28 diagnosed in the first 24 months vs 38 later) and with different duration of
      the diet (16 in gluten free diet for less than 12 months, 11 for less than 24
      months, and 39 for more than 24 months). RESULTS: Overall we did not find any
      significant difference in body composition between overall celiac patients and
      controls. However the fat mass, the body mass index, and the spine bone mineral
      density values in late diagnosed celiac patients were significantly lower than in
      early diagnosed patients (significance values were p < 0.009; p < 0.002; p <
      0.002, respectively). Patients on diet for less than 12 months showed
      significantly lower bone mineral content and density than those on diet for more
      than 24 months (significance values were, respectively, p < 0.011 and p < 0.022).
      Spine mineral density was the only parameter significantly influenced both by age
      at diagnosis (p < 0.03) and duration of gluten free diet (p < 0.008).
      CONCLUSIONS: Only an early diagnosis of celiac disease in pediatric age and a
      strict gluten free diet, lasting more than 12 months, allow celiac patients to
      reach a normal mineralization.

PMID- 9260801
TI  - Luminal antigliadin antibodies in small intestinal bacterial overgrowth.
AB  - OBJECTIVE: Elevated antigliadin antibody levels in small intestinal luminal
      secretions of subjects with normal or only mildly abnormal small intestinal
      histology are considered indicative of "latent" or "potential" celiac disease.
      The purpose of this study was to determine whether small intestinal bacterial
      overgrowth (SIBO) might provide an alternative explanation for positive luminal
      antigliadin antibodies in such subjects. METHODS: Twenty-six adult subjects
      without predisposition to disturbed mucosal immunity were investigated with
      culture of small intestinal luminal secretions. Luminal total IgA and IgA
      antigliadin antibody concentrations were measured by radial immunodiffusion and
      indirect enzyme immunoassay, respectively. Local mucosal counts of IgA-plasma
      cells were determined by immunohistochemistry. Small intestinal histology and
      intraepithelial lymphocyte counts were assessed by light microscopy.
      Corresponding serum antigliadin antibody concentrations were determined. RESULTS:
      SIBO was present in 17/26 (65.4%) subjects. No subject with SIBO had villous
      atrophy. Luminal total IgA concentrations (p < 0.0005), mucosal IgA-plasma cell
      counts (p < 0.01), and intraepithelial lymphocyte counts (p < 0.01) were
      significantly increased in subjects with SIBO. Luminal IgA-antigliadin antibodies
      were detected in 6/17 (35.3%) subjects with SIBO and 0/9 (0%) subjects without
      SIBO. Luminal IgA-antigliadin antibody concentrations correlated significantly
      with luminal total IgA levels (p < 0.01) but not with serum values (p < 0.1).
      Serum IgG-antigliadin antibody concentrations were elevated in 2/6 (33.3%)
      subjects with SIBO and positive luminal antigliadin antibodies. CONCLUSIONS: SIBO
      may be an alternative explanation to "latent" or "potential" celiac disease for
      positive luminal antigliadin antibodies in subjects with either normal or only
      mildly abnormal small intestinal histology, even when serum antigliadin antibody
      concentrations are elevated. Positive luminal antigliadin antibodies in SIBO
      probably occur as epiphenomena in the context of a graded mucosal immune response
      to local bacterial antigens.

PMID- 9260802
TI  - Distribution of inducible nitric oxide synthase in ulcerative colitis.
AB  - OBJECTIVE: To investigate reports that the biosynthesis of nitric oxide (NO) is
      increased in the colonic mucosa of patients with active ulcerative colitis (UC),
      which suggests that serum NOx levels may be an important indicator of UC
      activity. METHODS: To determine the role of NO within the colon, we purchased
      polyclonal antibodies against human-inducible NO synthase (iNOS). We then
      examined the distribution of iNOS-reactive cells in UC colon tissues. RESULTS: In
      specimens from 12 UC patients, iNOS-positive neutrophils and macrophages were
      observed at the base of the ulcer but not in distant areas in the active stage.
      iNOS expression in colon mucosa was virtually absent during the inactive stage of
      UC and within the colon of patients with non-UC colitis. CONCLUSIONS: We conclude
      that NO in colonic mucosa may play a potential role in the pathogenesis of UC.

PMID- 9260803
TI  - Mucosal interleukin-8 is involved in neutrophil migration and binding to
      extracellular matrix in inflammatory bowel disease.
AB  - OBJECTIVES: In this study, our purpose was to determine whether locally generated
      interleukin-8 (IL-8) is involved in neutrophil migration and binding to
      extracellular matrix, using the colonic mucosal specimens obtained from patients
      with inflammatory bowel disease (IBD). METHODS: Levels of IL-8 secreted in the
      organ cultures were measured by enzyme-linked immunosorbent assay. Chemotactic
      activity and binding capacity of neutrophils were induced by the organ culture
      supernatants. RESULTS: Significantly higher levels of IL-8 were secreted in
      patients with IBD, and its elevation was more prominent in patients with active
      ulcerative colitis. The organ culture supernatants induced higher chemotactic
      activity and binding capacity of neutrophils in patients with IBD, especially in
      those with active ulcerative colitis, compared with controls. These effects were
      inhibited significantly when the supernatants were submitted to preincubation
      with neutralizing anti-IL-8 antibody. CONCLUSIONS: Increased mucosal generation
      of IL-8 may attract neutrophils from the circulation into the inflammatory site
      and induce binding of neutrophils in the interstitial tissue, contributing to
      accumulation and activation of neutrophils in the affected mucosa with IBD.

PMID- 9260804
TI  - Esophageal reflux after total or proximal gastrectomy in patients with
      adenocarcinoma of the gastric cardia.
AB  - OBJECTIVES: To demonstrate gastroesophageal reflux induced by proximal
      gastrectomy and to report preventive measures, such as total gastrectomy followed
      by Roux-en-Y esophagojejunostomy. METHODS: Thirteen patients underwent proximal
      gastrectomy (PG), and six patients underwent total gastrectomy (TG). Two of the
      13 patients who received PG later underwent completion total gastrectomy. All
      patients were followed with endoscopy, radionuclide scintigraphy, and 24-h pH
      monitoring. RESULTS: Endoscopic examination revealed evidence of esophagitis in
      all PG group patients; however, none of the TG group had esophagitis. Prolonged
      esophageal transit was observed in 11 patients (10 in the PG group, one in the TG
      group). Increased residual fraction was found in 10 patients (nine in the PG
      group, one in the TG group). An increase in the retrograde index was found in 14
      cases (11 in the PG group, three in the TG group). Positive
      enterogastroesophageal reflux was identified in 11 patients (eight in the PG
      group, three in the TG group). Twenty-four hour pH monitoring resulted in 10
      positives (10 in the PG group, none in the TG group). CONCLUSIONS: Frequently,
      proximal gastrectomy will lead to significant gastroesophageal reflux and,
      subsequently, to varying degrees of esophagitis. The clinical symptoms are
      usually characteristic. However, the severity of esophagitis and the mechanism of
      reflux can be determined only by integrated interpretation of a reflux study. The
      study should include endoscopy, radionuclide scintigraphy, and 24-h pH
      monitoring. Although a total gastrectomy with Roux-en-Y diversion can reduce the
      incidence of acid reflux, neutral enteroesophageal reflux may be observed during
      a radioactive isotope study. Fortunately, neutral refluxes rarely cause
      esophagitis. A proximal gastrectomy should be avoided in adenocarcinoma of the
      gastric cardia, except in early cancer. Symptomatic palliation can be relieved by
      medication. However, completion total gastrectomy is the only effective method
      for eradicating unrelenting symptoms.

PMID- 9260805
TI  - Cholecystectomy-induced gastroesophageal reflux: is it reduced by the
      laparoscopic approach?
AB  - OBJECTIVE: The incidence of gastroesophageal reflux and esophagitis increases
      significantly following cholecystectomy. Laparoscopic technique minimizes the
      metabolic and mechanical disturbances of cholecystectomy, but there has been no
      study of its effects on gastroesophageal reflux. The aim of this study was to
      examine the effect of laparoscopic cholecystectomy on the indices of
      gastroesophageal reflux. METHODS: A prospective study was carried out on patients
      scheduled for cholecystectomy. Informed consent was obtained. Preoperative 24-h
      pH studies and manometry were performed. Studies were repeated 3 months after
      surgery. Pathological acid reflux was defined in terms of the DeMeester acid
      score. RESULTS: Pre- and postoperative studies were carried out on 28 patients
      who had open cholecystectomy and on 22 patients who had laparoscopic
      cholecystectomy. The mean (SEM) DeMeester acid score increased from 14.8 (2.4) to
      34.0 (6.7) following open cholecystectomy (p = 0.006) and from 13.9 (2.5) to 28.9
      (4.3) following laparoscopic cholecystectomy (p = 0.002). Decrease in mean lower
      esophageal sphincter pressure in both groups was not significant. CONCLUSIONS: A
      significant increase in the incidence of gastroesophageal reflux occurred within
      3 months after surgery in both study groups. Despite the less invasive nature of
      laparoscopic cholecystectomy, the type of surgery did not influence the degree of
      esophageal dysfunction.

PMID- 9260806
TI  - Better survival in women with resected hepatocellular carcinoma is not related to
      tumor proliferation or expression of hormone receptors.
AB  - OBJECTIVE: There is a well known male predominance in hepatocellular carcinoma
      (HCC). Moreover, female patients with HCC have better survival and lower
      recurrence rates after surgical resection. We previously showed that the better
      prognosis in female patients is related to a higher incidence of tumor
      encapsulation and less invasive tumors. However, the underlying mechanism is
      still obscure. METHODS: In this study, we examined the cell proliferative indices
      (expression of proliferative cell nuclear antigen (PCNA) and Ki-67 antigen using
      MIB1 antibody) and expression of the estrogen and progesterone receptors (ERs and
      PRs, respectively) in 71 patients with resected HCC. These were correlated with
      the pathological features of the tumors and the survival rates of patients.
      RESULTS: Female patients with HCC had significantly better actuarial and disease
      free survival rates than male patients (p = 0.010 and 0.004, respectively). Tumor
      PCNA scores, represented by positively stained nuclei per 1000 tumor cells, were
      significantly higher in tumors showing venous permeation (p = 0.034), positive
      resection margins (p = 0.011), and absence of bile production (p = 0.008). Higher
      tumor MIB1 scores were seen in tumors that had poorer cellular differentiation (p
      = 0.002) and no tumor capsules (p = 0.042). However, both tumor PCNA and MIB1
      scores did not differ significantly between female and male patients. ERs were
      detected in the tumor cells in 23.9% of tumors, and PRs were detected in 14.3%.
      Expression of both ER and PR was not influenced by gender. CONCLUSIONS: Women
      with HCC had significantly better survival and lower tumor recurrence rates.
      However, significant differences in cellular proliferation indices and expression
      of ER and PR were not observed between men and women to explain the difference in
      survival rate.

PMID- 9260807
TI  - Charcoal deposits in the esophageal and gastric mucosa.
AB  - We report the case of a 75-yr-old woman referred for gastrointestinal endoscopy
      to investigate severe iron deficiency anemia. Black linear lesions were observed
      in the distal esophagus and stomach. Biopsies revealed aggregates of coarse black
      foreign material, which was later identified as charcoal. The patient's previous
      medical history included an antidepressant overdose 5 yr before the current
      admission. The patient had a gastric lavage, using a large bore orogastric tube,
      followed by the administration of activated charcoal. The patient had no other
      history of charcoal ingestion. We propose that the charcoal became entrapped in
      mucosal tears caused by the traumatic intubation 5 yr previously, causing the
      incidental mucosal tattooing seen at endoscopy.

PMID- 9260809
TI  - Menetrier's disease: report of a transient case associated with chylous ascites.
AB  - We present a case of transient Menetrier's disease (MD) that was associated with
      chylous ascites. Using immunohistochemistry, we studied the expression of
      transforming growth factor alpha in this patient's gastric mucosa biopsy over
      time; a growth factor that has previously been shown to play an active role in
      the pathogenesis of MD. Excessive expression and altered localization of
      transforming growth factor alpha was observed while the patient had active
      disease with return to the normal pattern after resolution of the disease. This
      case is the first one reported of transient MD associated with chylous ascites;
      it lends further credible evidence to the concept that altered transforming
      growth factor alpha expression may play an important role in the pathogenesis of
      MD.

PMID- 9260808
TI  - Digestive manifestations in an immunocompetent adult with varicella.
AB  - A case of varicella with pancreatic pain as a first manifestation, a typical
      papulovesicular rash, pulmonary and hepatic and esophageal localizations
      occurring in an immunocompetent adult is reported. Treatment with intravenous
      acyclovir resulted in a prompt improvement and recovery in less than 4 days.

PMID- 9260810
TI  - Gastric Crohn's disease complicated by adenocarcinoma of the stomach: case report
      and review of the literature.
AB  - Patients with Crohn's disease are at increased risk for developing adenocarcinoma
      of the small bowel and colon. Although several cases of gastric malignancy have
      been reported in patients with Crohn's disease, the association remains
      controversial, particularly because most patients have not had gastric Crohn's
      involvement. We report a patient with long-standing Crohn's disease, with gastric
      involvement, who developed adenocarcinoma of the gastric outlet. We discuss the
      association and include a review of the literature.

PMID- 9260811
TI  - Paradoxical cerebral emboli after transjugular intrahepatic portosystemic shunt
      and coil embolization for treatment of duodenal varices.
AB  - The use of the transjugular intrahepatic portosystemic shunt to treat portal
      hypertension has resulted in increased recognition of its associated
      complications. We report a patient with refractory duodenal variceal bleeding
      treated with transjugular intrahepatic portosystemic shunt, as well as coil
      embolization, who subsequently developed bilateral cerebral and cerebellar
      infarcts consistent with arterial emboli. This complication has not been
      previously described. The patient was found to have a patent foramen ovale and a
      right to left intracardiac shunt leading to paradoxical embolization of clots
      traveling from portal to systemic venous circulation, then to the left atrium.
      With the relative frequency of patent foramen ovale in the population, our
      observation has potential importance for patients with right to left cardiac
      shunts who are being considered for portosystemic shunt procedures, or who are
      undergoing embolization of bleeding varices.

PMID- 9260812
TI  - Low epithelial cell proliferation and absence of oncoprotein expression in
      juvenile polyposis of the stomach, with or without tumors.
AB  - OBJECTIVES: To assess cell proliferation and analyze oncogenetic abnormalities in
      cases of juvenile polyposis of the stomach (JPs), with or without coexisting
      tumors. METHODS: The Ki-67 labeling indices (KLI) were compared for juvenile
      polyps and coexisting tumors in three cases of JPs along with values for
      gastritis, foveolar epithelial hyperplastic polyps, adenomas, and carcinomas.
      Expression of p53, Bcl-2, and c-ErbB-2 in tumors was examined
      immunohistochemically, and a search for c-Ki-ras mutations was made by DNA direct
      sequencing. RESULTS: The KLI for JPs did not significantly differ between cases,
      being consistently lower than the values for both hyperplastic polyps and
      gastritis. The KLI for the papillary tumors and a signet ring cell carcinoma
      found in association with JPs tended to be lower than those for their
      conventional counterparts. P53, but not Bcl-2 and c-ErbB-2, was focally expressed
      in the papillary tumors, whereas all three were absent in the signet ring cell
      carcinoma, in the JPs. No c-Ki-ras mutations were detected in the papillary
      tumors. CONCLUSIONS: The cell proliferation of JPs is relatively low and the
      polyps can be considered hamartomatous. However, neoplastic change clearly can
      occur in association with a relative increase in proliferative activity being
      observed in coexisting tumors. Low cellular proliferative activity and absence of
      oncogenetic abnormalities in tumors of JPs, compared with their conventional
      counterpart tumors, suggest that pathways of tumorigenesis and genetic alteration
      in JPs may be different from those in their conventional counterparts.

PMID- 9260813
TI  - Pernicious anemia and gastric carcinoid tumor: case report and review.
AB  - Gastric carcinoid tumors are being recognized increasingly in patients with
      pernicious anemia. Such tumors occur in the presence of achlorhydria, chronic
      atrophic gastritis involving the fundus and body of the stomach,
      hypergastrinemia, and enterochromaffin-like cell hyperplasia-dysplasia. A 74-yr
      old man with a 6-yr history of pernicious anemia who developed a solitary gastric
      carcinoid tumor of the corpus is described. The patient presented with
      hematemesis and was treated endoscopically. A total of 136 patients with
      pernicious anemia-associated gastric carcinoids have been described in the
      literature. Their clinical characteristics are also reviewed.

PMID- 9260814
TI  - Esophageal metastasis from clear cell carcinoma of the kidney.
AB  - Esophageal metastasis from distant primary malignancies is an uncommon
      occurrence. The first case of a clear cell carcinoma of the kidney metastatic to
      the esophagus 5 yr after nephrectomy is reported.

PMID- 9260815
TI  - Fatal strongyloidiasis in a patient with ulcerative colitis after corticosteroid
      therapy.

PMID- 9260816
TI  - Beclomethasone dipropionate administration via cecostomy in ulcerative colitis.
AB  - Beclomethasone dipropionate was administered via a cecostomy to four patients
      with active ulcerative colitis that was refractory to conventional
      glucocorticosteroid therapy. From a tube cecostomy, beclomethasone dipropionate
      solution was administered continuously throughout the day. Clinical
      manifestations, laboratory examinations, and endoscopic and/or radiographic
      findings markedly improved within 1-2 wk. A serial decrease in the index of
      disease activity was observed from the time administration began (mean score,
      226.0) to 2 wk later (137.4 points). An excellent clinical response was
      recognized without any significant side effects, and the urgent need for total
      colectomy was avoided in all four patients.

PMID- 9260817
TI  - Spontaneous rupture of the liver in amyloidosis.
AB  - Hepatic rupture is an unusual complication of hepatic amyloidosis. We report the
      case of a 59-yr-old man with a subcapsular hematoma of the liver with hepatic
      rupture secondary to amyloidosis. The patient died during the surgery. The
      etiology, pathology, diagnosis, and treatment of this complication are discussed.
      Previously reported cases of subcapsular hematoma of the liver secondary to
      amyloidosis are reviewed. This knowledge and an awareness of the possible
      diagnosis will help to decrease the high mortality rate associated with this
      complication.

PMID- 9260818
TI  - Sertraline, a selective serotonin reuptake inhibitor, unmasking carcinoid
      syndrome.

PMID- 9260819
TI  - Suprahepatic gallbladder associated with cholelithiasis.

PMID- 9260820
TI  - Occurrence of hepatocellular carcinoma in a case of hereditary coproporphyria.
AB  - An association between two types of acute hepatic porphyria (porphyria variegata
      and acute intermittent porphyria) and hepatocellular carcinoma has previously
      been reported. In these studies, etiological factors for hepatocellular carcinoma
      were not completely sought. We report here the first case of an association
      between hepatocellular carcinoma and hereditary coproporphyria, the third type of
      acute hepatic porphyria. A 58-yr-old woman with hereditary coproporphyria
      presented with a 3.5-cm-diameter hepatocellular carcinoma. Results of exhaustive
      investigation of etiological factors for hepatocellular carcinoma were negative.
      Results of microscopic histological analysis of the nontumorous liver were
      normal. Five years after surgical resection, the patient had no evidence of tumor
      recurrence.

PMID- 9260821
TI  - False elevation of CA 19-9 levels in a patient with a history of pancreatic
      cancer.
AB  - CA 19-9 is the most sensitive and specific marker currently used in the diagnosis
      of pancreatic cancer. Its interpretation, however, can be limited in the presence
      of certain nonmalignant diseases that have been correlated with elevated serum
      levels of CA 19-9. We report an unusual case of falsely elevated CA 19-9 levels
      in a patient with a history of resected pancreatic cancer. This patient presented
      4 yr after resection with painless jaundice and markedly elevated CA 19-9 levels
      (2327 U/ml). Although it was initially suspected that the patient had recurrent
      cancer, further evaluation proved that her jaundice and increased CA 19-9 value
      were due to a benign stricture that led to cholestatic jaundice and concomitant
      cholangitis. No previous cases of falsely elevated CA 19-9 levels have been
      reported in the context of a known history of pancreatic cancer. Physicians
      should be aware of the perturbations that extrahepatic cholestasis and certain
      inflammatory diseases of the pancreas and hepatobiliary system may impose on CA
      19-9 levels. Furthermore, this case demonstrates that even markedly elevated CA
      19-9 levels in patients being assessed for recurrence of pancreatic cancer need
      to be carefully interpreted in the context of other clinical findings.

PMID- 9260822
TI  - Hepatic artery pseudoaneurysm associated with amebic liver abscess presenting as
      upper GI hemorrhage.
AB  - We report the case of a 40-yr-old man who presented with recurrent hemorrhage of
      the upper GI tract who was found to have hepatic artery pseudoaneurysm and amebic
      liver abscess. Our patient is unique in having hepatic artery pseudoaneurysm and
      amebic liver abscess diagnosed simultaneously, the association of which has not
      been previously described.

PMID- 9260823
TI  - Esophageal variceal sclerotherapy or band ligation: is two better than one?

PMID- 9260824
TI  - EUS for common bile duct stones: time to harness the power.

PMID- 9260825
TI  - Magnetic resonance cholangiopancreatography versus ERCP: the "superbowl" of
      pancreaticobiliary imaging.

PMID- 9260826
TI  - Re: a prospective comparison of laparoscopy and imaging in the staging of
      esophagogastric cancer before surgery.

PMID- 9260827
TI  - Re: manometric tests of anorectal function in the management of defecation
      disorders.

PMID- 9260828
TI  - Heterozygous familial hypobetalipoproteinemia associated with fatty liver.

PMID- 9260829
TI  - Extrahepatic manifestations of hepatitis C virus infection.

PMID- 9260830
TI  - Re: J.M. Kremer--editorial.

PMID- 9260831
TI  - Re: anxiety in patients submitted to endoscopy.

PMID- 9260832
TI  - GB virus infection in acute and chronic cryptogenic liver disease.

PMID- 9260833
TI  - Cytodifferentiation of trophoblast in the anchoring villi and trophoblastic shell
      in the first half of gestation in the macaque.
AB  - The structure of cytotrophoblast cells in cell columns of the anchoring villi and
      trophoblastic shell were studied by light and transmission electron microscopy
      during days 19-70 of pregnancy in the macaque. Additional placentas were prepared
      for 3H-thymidine autoradiography to demonstrate DNA synthesis. The cell columns
      of the anchoring villi consist of proximal, mid, and distal regions, and
      similarly the trophoblastic shell has a region forming the base of the
      intervillous space, a central zone, and a junctional zone. The proximal region of
      the cell column is composed of closely apposed, largely undifferentiated
      cytotrophoblast cells lacking intercellular space. In the mid region, the cells,
      which contain segregated glycogen areas, are separated into branching strands by
      extensive extracellular matrix. The distal zone abuts the trophoblastic shell and
      has fewer mostly peripheral cytotrophoblast cells and abundant matrix. Where
      cytotrophoblast of the shell is exposed to intervillous space or underlies
      syncytial trophoblast bordering the intervillous space, pads of cuboidal cells
      are seen. The central zone of the shell is arranged in strands of contiguous
      cells. Near the maternal junctional zone, the cells have fewer junctional regions
      and contain lipid rather than glycogen. Results of thymidine incorporation
      studies are consistent with observations of others using Ki67 distribution,
      indicating that cell replication occurs in the proximal region of the cell
      column, with subsequent migration of cells into the trophoblastic shell. Changes
      with age include an increase in extracellular matrix in the proximal region, a
      more linear organization in the expanded central zone of the shell, and a
      decrease in necrosis at the junction of the shell with endometrium, resulting in
      close association of shell cytotrophoblast cells, maternal decidual cells, large
      granular lymphocytes, and macrophages. It is concluded that the cytotrophoblast
      of the cell columns and trophoblastic shell is a pleomorphic cell type responding
      to adjacent constituents including the matrix it forms.

PMID- 9260834
TI  - Regulation of gap junctional communication during human trophoblast
      differentiation.
AB  - During pregnancy, the trophoblast, supporting the main functions of the placenta,
      develops from the fusion of cytotrophoblastic cells into a syncytiotrophoblast.
      Gap junction channels consisting of connexins link the cytosols of cells in
      contact. Gap junctional communication has been involved in the control of cell
      and tissue differentiation. Recently, a gap junctional communication was
      demonstrated in trophoblast cell culture by means of the fluorescence recovery
      after photobleaching (gap-FRAP) technique. This gap junctional communication
      appeared to be stimulated by human chorionic gonadotropin (hCG). Therefore, the
      specificity of hCG action and the signalling mechanisms implicated in gap
      junctional communication were investigated by means of gap-FRAP. In culture,
      cytotrophoblastic cells develop into cellular aggregates, then into a syncytium,
      within 1-2 days after plating. During this in vitro differentiation, gap
      junctional communication was measured, and the maximum percentage of coupling
      between adjacent cells occurred on the fourth day. In the presence of 500 mIU/ml
      hCG, the percentage of coupled cells was increased at all stages of culture, and
      the highest proportion of coupled cells was observed after 2 days instead of 4
      days in control conditions. The hCG action was specific, since the addition of
      heat-inactivated hCG of oFSH or of bTSH did not affect gap junctional
      communication in trophoblastic cells. The addition of a polyclonal hCG antibody
      decreased basal gap junctional communication as well as the response to exogenous
      hCG. Moreover, the presence of 8Br-cAMP (0.5 or 1 mM) mimicked the stimulation by
      hCG. Interestingly, H89 (2 microM), a specific protein kinase-A inhibitor,
      dramatically decreased the responses to hCG (500 mIU/ml) and the 8Br-cAMP (0.5
      mM) stimulation of trophoblastic gap junctional communication. Calphostin (1 or 2
      microM), a specific protein kinase-C inhibitor, strongly stimulated gap
      junctional communication. In conclusion, the demonstration by means of the gap
      FRAP method of a gap junctional communication preceding cellular fusion could be
      considered as an objective and physiological criterion to mark the beginning of
      trophoblast differentiation. hCG, a hormone produced by the trophoblast, and two
      signalling mechanisms are implicated in this phenomenon.

PMID- 9260836
TI  - Immunohistochemical localization of fibrillin in developing macaque and term
      human placentas and fetal membranes.
AB  - The objective of this study was to examine the developmental appearance of the
      extracellular matrix glycoprotein fibrillin in macaque placentas and fetal
      membranes and to compare this distribution to that seen in term human placentas
      and fetal membranes. Standard immunoperoxidase methods were used on
      paraformaldehyde-fixed, paraffin-embedded tissues. At early gestational ages (26
      30 days), fibrillin was found in cell columns and cytotrophoblastic shell, with
      weak staining in the villous stroma. Staining was abundant in the shell and
      columns at 53 days as well, and stronger staining was seen in the stroma of the
      chorionic plate and stem villi. Staining in the shell and remnants of the cell
      columns in later gestation continued to be positive, though variable. Generally,
      the strongest staining was present in the distal cytotrophoblastic shell. Stroma
      in the tips of anchoring villi was also strongly positive. Later in gestation,
      fibrillin was observed around the multilayered cytotrophoblast of the chorionic
      plate. Fibrillin was abundant in the stromal cores of human term placental villi.
      In early macaque amnion, fibrillin staining was abundant in a layer beneath the
      amniotic epithelium. Later in gestation, macaque chorioamnion staining was
      generally similar to human term chorioamnion staining, with the heaviest staining
      in portions of the compact and reticular layers. Fibrillin was sometimes
      localized in regions known to be rich in connective tissue microfibrils, but, in
      other regions known to have abundant microfibrils, fibrillin staining was weak.
      This suggests that some microfibrils in placenta may be composed predominantly of
      some other protein(s). The function of fibrillin in the various placental
      compartments is unknown at present. It may provide attachment points for cells
      while at the same time providing a strong, yet flexible, matrix to accommodate
      growth particularly in areas subject to shear stress.

PMID- 9260835
TI  - Classification of human placental stem villi: review of structural and functional
      aspects.
AB  - The stem villi of the human placenta represent the central branches of the
      villous trees. They are characterized by a condensed fibrous stroma in which the
      fetal arteries and veins as well as the arterioles and venules are embedded.
      Functionally they are accepted as the mechanically supporting structures of the
      villous trees, and they are supposed to control fetal blood flow to the
      maternofetal exchange area, which is located in the peripheral villi. To obtain
      further insights into the functions of the stem villi, the recent literature has
      been reviewed, and some immunohistochemical, ultrastructural, and reconstruction
      studies have been added. These new studies were aimed at identifying
      immunohistochemically different subtypes of stem villi, their branching patterns,
      the distribution of macrophages, the stromal proliferation patterns, and the
      differentiation of extravascular stromal cells. Our findings demonstrate that the
      stem villi and their precursors, the immature intermediate villi, can selectively
      be identified by anti-gamma-smooth muscle (sm) actin staining. Furthermore, the
      existence of three different subtypes of stem villi is shown; these differ
      regarding the presence and distribution of gamma-sm actin-positive cells. These
      cells were immunohistochemically and ultrastructurally identified as smooth
      muscle cells and myofibroblasts. Increasingly complex coexpression patterns of
      cytoskeletal proteins reflect a clearly defined differentiation gradient of
      extravascular stromal cells, which covers the whole range of an undifferentiated
      germinative layer beneath the trophoblast to highly differentiated myofibroblasts
      surrounding the medias of the stem vessels. Possible functions of the
      extravascular contractile system include the regulation of villous turgor and the
      control of intervillous blood flow impedance.

PMID- 9260837
TI  - Pressure dependence of so-called transtrophoblastic channels during fetal
      perfusion of human placental villi.
AB  - To test the influence of perfusion pressures on structural preservation of human
      placental villi and on the dilatation of the so-called transtrophoblastic
      channels, cotyledons of 32 term human placentas have been perfused in vitro.
      Periods of perfusion with isotonic Ringer solution under various arterial and
      venous hydrostatic pressures were followed by perfusion fixation. In some
      experiments, lanthanum hydroxide as an extracellular marker was added to the
      fixative. Distention of the fetal vascular system, stromal edema and continuity,
      as well as trophoblastic vacuolization were studied via electron microscopy with
      subsequent morphometry. The findings suggest that arterial hydrostatic pressures
      in the perfusion system of about 80 cm H2O are needed to guarantee homogeneous
      perfusion of the fetal vascular system. To avoid stromal edema and trophoblastic
      vacuolization, venous hydrostatic pressures of 4 cm H2O and arterial hydrostatic
      pressures of 80 cm H2O should not be exceeded. It is concluded that the
      trophoblastic vacuoles are dilated segments of the so-called transtrophoblastic
      channels. The functional importance of in vivo variations of fetal intravascular
      hydrostatic pressure for the dilatation of transtrophoblastic channels and for
      fetal water balance is discussed.

PMID- 9260838
TI  - Location of insulin receptors in the placenta and its progenitor tissues.
AB  - The insulin receptor gene is constitutively expressed, so the presence of insulin
      receptor proteins might be expected on all mammalian tissues, with the plasma
      membrane as the predominant site of receptor location. Results reviewed here
      indicate that insulin receptors are also present in all placental tissues and the
      placenta's progenitor tissues and cells, i.e., oocytes, spermatozoa, and
      preimplantation embryos, in most of the species studied. Receptor densities,
      however, vary among individual cells and cell types and at various developmental
      stages. Three aspects deserve emphasis. 1) In human placenta, the insulin
      receptor distribution pattern is characterized by a spatiotemporal change between
      first trimester and term. At the beginning of pregnancy, insulin receptors are
      found predominantly on the maternal side (apical membrane of syncytiotrophoblast,
      low density on cytotrophoblast); at term, however, they are on the fetal side
      (lining the fetal vessels). This suggests that, in the first trimester, maternal
      insulin regulates insulin-dependent processes, whereas, at term, it must be fetal
      insulin mainly controlling these processes. 2) The majority of insulin receptors
      is expressed on structures that are currently assumed to drive placental growth,
      i.e., syncytial sprouts and mesenchymal villi in first-trimester placentas and
      fetal endothelium at term. Therefore, we hypothesize a growth-promoting function,
      among others, of insulin on the placenta. 3) At present, no histologic evidence
      is available to demonstrate insulin receptors in structures commonly associated
      with receptor-mediated endocytosis. Whether placental insulin receptors are
      internalized, therefore, awaits clarification.

PMID- 9260839
TI  - Placental vascular corrosion cast studies: a comparison between ruminants and
      humans.
AB  - The microvasculature of both the ruminant placentomes of cattle, sheep, and goats
      and the human placenta were compared, using corrosion casts of blood vessels and
      scanning electron microscopy. The fetal vascular trees of ruminant and human
      placenta differ in form and size, which correlates with the degree of
      ramification; however, their architecture of stem, intermediate, and terminal
      villi is similar. In the human, the system of serially linked capillary
      convolutions of terminal villi is longer than that in ruminants. Therefore, in
      guaranteeing blood flow against flow resistance, the human vessels particularly
      need a straight course, anastomoses, and sinusoidal dilations. Specifically in
      the ruminants studied, the venous vessels outweigh the arterial ones by volume
      and by number. They are suggested to be absorptive for substances metabolized in
      the zone of the capillary complex. The most extreme interspecies difference
      relates to the maternal vasculature, which, in contrast to the fetal system, is a
      closed system in the ruminant septas and an open lacunal intervillous space in
      the human. Converging and differing morphological vascular phenomena of ruminants
      and human placenta are discussed in terms of maternofetal exchange related to
      placental efficiency. In summary, the ruminant placenta, concerning the fetal
      vascular tree, in many aspects is workable as a model for the human.

PMID- 9260840
TI  - Structure and function in the ruminant synepitheliochorial placenta: central role
      of the trophoblast binucleate cell in deer.
AB  - The ruminant placenta has a very uniform gross structure based on localised areas
      of fetomaternal membrane apposition and proliferation to form placentomes. There
      is no consistency, however, in the number or size of these placentomes (6-150),
      nor in the villus architecture of the individual placentome. The one consistent
      feature is the binucleate cell (BNC) population in the trophoblast. These BNC
      form 15-20% of the epithelium in all ruminants examined so far. They synthesise
      the placental lactogen hormone and other glycoproteins and migrate through tight
      junctions to fuse with a uterine epithelial cell to form initially fetomaternal
      hybrid trinucleate cells (TNC) and subsequently syncytial plaques (SP). Such SP
      may be transient or persist throughout pregnancy depending on the species. The
      wide range of deer species examined confirms the uniformity of the BNC hormone
      production, migration, and fusion pattern described for other ruminants. BNC
      migration produces predominantly transient TNC, but there are areas of SP largely
      restricted to the apex of the maternal crypts. Maternal large granule lymphocytes
      (LGL) are uniquely found in deer placentomal uterine epithelium; they are usually
      closely associated with TNC and SP sites, but the significance of the
      interactions remains to be established.

PMID- 9260841
TI  - Localisation of glycans in the placenta: a comparative study of epitheliochorial,
      endotheliochorial, and haemomonochorial placentation.
AB  - Specimens of mid-term (horse), near-term (pig, cow, sheep, mink) and term (human)
      placentae and associated tissues have been examined with a panel of 15
      biotinylated lectins combined with an avidin-peroxidase revealing system. The aim
      of this study has been to analyse the expression of glycans at the materno-fetal
      interface in order to establish whether the morphological diversity exhibited by
      these six species is reflected by accompanying biochemical diversity, or whether
      similar types of glycan are expressed in tissues performing similar functions.
      Lectin staining intensity was scored in the following elements of the interhaemal
      placental barrier: maternal capillaries, maternal uterine epithelium, the materno
      fetal interdigitating microvillous membrane (brush border in the human),
      trophoblast, and fetal capillaries. A high degree of biochemical diversity was
      found in the glycan expression of the various placental components within and
      among placental types. Each layer showed widely differing patterns of lectin
      binding between species, with only a few findings in common: 1) the relative lack
      of simple fucosyl termini, 2) the presence of non-bisected bi/tri-antennary N
      glycan in most layers, 3) an abundance of terminal N-acetyl galactosamine, and 4)
      the restriction of high mannose glycans to intracellular granules. This diversity
      may be a mechanism to avoid hybridisation, although glycan patterns may change
      between conception and placental development, or it may have evolved as a
      consequence of morphological changes. It is possible that it may also be part of
      the cause, rather than the result, of the structural diversity that is so
      characteristic of mammalian placentation.

PMID- 9260842
TI  - Carbonic anhydrase activity in different placenta types: a comparative study of
      pig, horse, cow, mink, rat, and human.
AB  - The placenta has multiple functions, being the organ which provides oxygen and
      nutrients to the developing conceptus. In the placenta, the enzyme carbonic
      anhydrase (CA) may provide ions for exchange with Na+, K+, and Cl- in
      transepithelial movement of ions and fluid, as well as facilitating carbon
      dioxide diffusion. It can also be active in intermediary metabolism, such as
      gluconeogenesis, urea, and fatty acid synthesis. Placental material from pig,
      horse, cow, mink, rat, and human was therefore investigated, representing
      placenta types with variations in shape, internal architecture, and nature of the
      interhemal barrier. After glutaraldehyde fixation, sections were stained by a
      histochemical CA-method demonstrating all active isozymes. The most striking
      feature in common was a positive reaction in the maternal capillaries, when
      present, as in pig, horse, cow, and mink. In the maternal epithelium, the
      activation of CA was only observed in the pig, which also exhibited the strongest
      activity at the maternal interface, which reacted moderately in rat, weakly in
      horse, and was not visible in cow and human. The trophoblast was positive in pig
      and rat, whereas it was negative in horse, cow, human, and mink placentae except
      for few scattered trophoblast cells in pig, horse, and cow, which showed very
      intense activity. In the fetal capillaries, a positive reactivity was only
      observed in mink and human. The utilization of CA in placental transfer and
      metabolism is thus highest in the pig, rat, and mink, compared with horse, cow,
      and human. It can therefore be concluded that the activation and localization of
      CA in the placental interhemal barrier varies considerably among species.

PMID- 9260843
TI  - Vascular interrelationships of near-term mink placenta: light microscopy combined
      with scanning electron microscopy of corrosion casts.
AB  - The microvasculature of the near-term zonary placenta of the mink has been
      studied using light microscopy and scanning electron microscopy of corrosion
      casts, prepared from maternal and fetal vessel systems, respectively. The zonary
      area, most important for placental exchange, includes a characteristic labyrinth.
      The labyrinth is composed of lobules oriented in a maternal-fetal direction. One
      maternal stem artery serves as the central axis of a lobule, and about six pairs
      of fetal stem arteries and stem veins of the chorionic primary villi mark the
      periphery of the lobule. Viewed from the fetal side of the labyrinth, this
      lobular structure presents a roughly hexagonal pattern, with the central maternal
      stem artery and radially oriented arteriolar branches giving the lobule the shape
      of a star. These arterioles frequently form bridges to neighboring lobular
      systems; however, the majority continue into the feto-maternally oriented three
      dimensional network of maternal capillary sinusoids, which converge on the
      outlets of the maternal stem veins on the maternal side of the labyrinth.
      Maternal main crypts are delimited by the rays of the star-shaped lobules
      containing chorionic primary villi. The latter penetrate into maternal crypts
      from the fetal side, and are characterized by their axial arterial and venous
      stem vessels. Fetal secondary villi are arranged at different levels from these
      stem vessels. The secondary villi are characterized by arterioles and venules
      branching in pairs from the stem vessels and supply the tributary capillary
      complexes of terminal villi. The lobular structure of the placental labyrinth
      provides a three-dimensional framework of vessels where maternal capillary
      sinusoids and fetal capillaries meet in a one-way cross-current arrangement. The
      blood flow conditions and the peculiarities of the mink placenta interhemal
      membrane are compared to those of other carnivores and discussed with respect to
      the efficiency of the endotheliochorial placenta.

PMID- 9260844
TI  - Structure and permeability of human placental microvasculature.
AB  - Endothelial paracellular junctions are important structures for the regulation of
      vascular permeability, junctional organisation being systematically related to
      the functional properties of the endothelium. Electron microscopic studies,
      immunocytochemistry, and single-passage permeability measurements have
      established that the placental microvessels resemble the fairly tight continuous
      microvessels of skeletal muscle both in structure and permeability. The
      endothelial paracellular clefts of these microvessels contain two distinct
      junctional entities which may influence permeability: the tight junction and the
      adherens junction. These clefts impose a substantial restriction to molecules
      above RMM 1000 Da and large haemproteins cannot cross the clefts. The 18 nm-wide
      zones of the clefts possess the transmembrane adhesion molecules PECAM-1 and VE
      cadherin, which have been implicated in junctional assembly and permeability.
      Inflammatory mediators such as histamine and tumour necrosis factor cause a
      redistribution of these adhesion molecules to non-junctional regions, and
      histamine (100 microM) causes a rapid and sustained rise in extraction of radio
      labeled tracers. Electron microscopy has also revealed possible first indications
      of tight junctional disassembly. Both the endothelia of larger placental vessels
      and isolated placental microvascular endothelial cells express cadherins and
      PECAM-1 and contain an extensive F-actin cytoskeleton, which is implicated in
      changes of cell shape and junctional assembly/disassembly. Thus, the human
      placental endothelium, using perfusion techniques and in vitro experiments,
      offers a valuable model for vascular permeability studies.

PMID- 9260845
TI  - Mechanism of glucose transport across the human and rat placental barrier: a
      review.
AB  - Glucose is one of the most important substances transferred from the maternal
      blood to the fetal circulation in the placenta, and its transport across the
      cellular membranes is mediated by glucose transporters. Facilitated-diffusion
      glucose transporter GLUT1 is abundant in the placental barrier, as is the case in
      other blood-tissue barriers, where GLUT1 is present at the critical plasma
      membranes of the barrier cells. In the human placenta, the microvillous apical
      and the basal plasma membranes of the syncytiotrophoblast are rich in GLUT1,
      which molecule seems to be responsible for the transcellular transport of glucose
      across the placental barrier. In the rat placental labyrinth, two layers of
      syncytiotrophoblasts (termed syncytiotrophoblasts I and II from the maternal
      side) serve as a barrier. GLUT1 is abundant at the plasma membrane of
      syncytiotrophoblast I facing the maternal side, and the plasma membrane of
      syncytiotrophoblast II facing the fetal side. Numerous gap junctions, made of
      connexin 26, connect syncytiotrophoblasts I and II, comprising a channel for the
      transfer of glucose between them. GLUT1 in combination with the gap junction,
      therefore, seems to serve as the structural basis for the transport of glucose
      across the rat placental barrier.

PMID- 9260846
TI  - Techniques of advanced light microscopy and their applications to morphological
      analysis of human extra-embryonic membranes.
AB  - The science of light microscopy has advanced dramatically in recent years through
      the introduction of new technology. A brief description of scanning light
      microscopes, laser illumination, the confocal principle, digital imaging, and
      image processing reveals a number of theoretical advantages which are
      particularly useful in improving epifluorescence microscope images. Examples of
      results from several studies of human extra-embryonic membranes conducted in our
      laboratory show how the application of these techniques has been used to describe
      structures such as microtrabeculae and rivets for the first time, to map the
      microscopic distribution of a wide range of proteins, and to observe the activity
      of placental villi at the microscopic level in an environmentally controlled
      microscope stage. High-sensitivity detectors have permitted the "super
      resolution" detection of structures smaller than the theoretically calculated
      limits of light microscope resolution. Rendering images in false colour is
      demonstrably useful in detecting subtle variations in fluorescence intensity at
      different intracellular sites and at different sites within tissues of fetal
      membranes. Processing stacks of digital images using appropriate software allows
      the 3-D reconstruction of suitably sized extra-embryonic membrane components.
      These digital images created from optical sections through the tissue are
      obtained non-destructively, and the relationships in space of the components are
      well preserved.

PMID- 9260848
TI  - Localization of human chorionic gonadoptropin and placental lactogen by
      immunogold labeling for electron microscopy: technique and limitations.
AB  - To demonstrate human chorionic gonadotropin (hCG) and human placental lactogen
      (hPL) secretory granules in placenta and to illustrate newer embedding techniques
      and specific immunospecificity problems in the placenta, labeling experiments
      using immunogold or peroxidase combined with avidin-biotin enhancement in epoxy
      LX-112-, Araldite-, or LR gold-embedded tissue fixed in 2.5% glutaraldehyde or
      2.5% paraformaldehyde were carried out in term and first-trimester normal human
      placenta and in partial hydatidiform moles. Increased sensitivity of the low
      temperature LR gold method was found for hPL-labeled granules. beta hCG-labeled
      granules were noted in syncytium of first-trimester placenta, and beta hCG
      containing granules in hydatidiform moles were similar to those of normal
      placenta. Paraformaldehyde fixation and LR gold embedding permitted
      identification of endoplasmic reticulum-associated labeling not observed with
      other methods. A brief review and discussion of immunolabeling methods, controls,
      and embedding materials is presented. We conclude that further refinement of
      peptide localization methods in the placenta is possible but must take into
      account the abundant potentially cross-reacting peptides present in the placenta.

PMID- 9260847
TI  - Immunocytochemical localization of growth factors and intermediate filaments
      during the establishment of the porcine placenta.
AB  - The immunocytochemical localization of insulin-like growth factor I (IGF-I) and
      platelet-derived growth factor A (PDGF-A) chain ligands, PDGF-chain receptors,
      and the intermediate filaments cytokeratin, desmin, and vimentin in the tissue
      reorganization and development during the establishment of the porcine
      epitheliochorial placenta was studied at light and electron microscopic levels in
      sections of endometrium and/or placenta of gilts during early pregnancy up to day
      40 postmating. The endometrial epithelia (surface and glandular) as well as the
      trophoblast showed PDGF-A and IGF-I labelling. The only temporal difference was
      seen regarding IGF-I labelling, this being more uniform in the glands during
      precontact and early contact stages (days 7-12) compared to later stages.
      Cytokeratin labelling was conspicuous in all epithelia, including the
      trophoblast. The endometrial stroma showed strong labelling for the PDGF
      receptors and the intermediate filament vimentin, staining being enhanced along
      with the increase in the vascular bed during the establishment of the placenta.
      The maternal endothelium immunoreacted to IGF-I, to both PDGF-A and PDGF
      receptors, to vimentin and to von Willebrand factor (Factor VIII). Desmin was
      also expressed in the capillary bed underneath the maternal surface epithelium.
      In larger blood vessels, desmin was detected in the smooth muscle layer but not
      in the endothelium. The vascular smooth muscle also reacted with IGF-I, PDGF-A,
      and PDGF-receptor antibodies. The results suggest the involvement of both growth
      factors, IGF-I and PDGF, in the early nutrition of the pig embryo and the tissue
      reorganization that encompasses placentation. IGF-I appears to be related to the
      secretory tissue compartment (formation of histotrophe), whereas PDGF might play
      a role in the reorganization of the stroma, particularly during placental
      angiogenesis. Desmin and von Willebrand factor immunolabelling appears to be
      useful to monitor the development of the subepithelial capillary bed in the
      porcine placenta.

PMID- 9260849
TI  - Cytokines in mammalian reproduction and speculation about their possible
      involvement in nonmammalian viviparity.
AB  - In recent years, the secretion of immunoregulatory factors (cytokines) at the
      maternofetal interface in mammals has been widely documented. Although cytokine
      production seems to be a specific phenomenon in mammalian reproduction, the
      specific roles of these substances in different species are still not clear.
      However, a balance of different cytokine activities appears to be crucial for
      regulation of the establishment and survival of the semiallogeneic embryo in
      maternal tissues. The apparent immunological role of placental cytokines in the
      mechanisms of implantation and embryonic development in mammals has raised the
      question of whether cytokines are also involved in the reproduction of
      nonmammalian vertebrates. Our studies have shown that the production of cytokines
      by the maternofetal unit is not limited to mammalian species, but that
      interleukin-1 (IL-1)alpha, IL-1beta, and transforming growth factor-beta (TGF
      beta) are secreted by the placenta of a viviparous squamate reptile, Chalcides
      chalcides. Our finding of this parallelism between reptilian and mammalian
      reproduction suggests that immunological mechanisms, possibly mediated by the
      secretion of cytokines, played an important role in the evolution of viviparity.

PMID- 9260850
TI  - Stereology and its impact on our understanding of human placental functional
      morphology.
AB  - The new stereology permits the objective, quantitative description of morphology
      by efficient and design-based methods. Applications to placentas in normal and
      abnormal pregnancies have proved of great value for challenging earlier
      misconceptions and interpreting better the processes of growth, morphogenesis,
      adaptation, and functioning at the whole-organ level. This contribution reviews
      the essential features of the stereological approach, identifies useful
      structural quantities, and provides examples of their application in various
      experiments of nature. We focus particularly on normal gestation and the effects
      of pregnancies associated with high altitude, maternal diabetes mellitus,
      preeclampsia, and maternal smoking.

PMID- 9260851
TI  - Hyperbaric oxygen--a neuroprotective adjuvant for hyperacute ischemic stroke?

PMID- 9260852
TI  - Experimental benznidazole encephalopathy: I. Clinical-neurological alterations.
AB  - Benznidazole (N-benzyl-2-nitro-1-imidazoleacetamide) is an antiprotozoan agent of
      the nitroimidazole group used extensively in South America to treat Chagas'
      disease. In humans, its most important side effect is peripheral polyneuropathy,
      the frequency of which is dose related. To evaluate this effect, we administered
      benznidazole to adult, male, mongrel dogs at doses ranging from 5 to 40 mg/kg/day
      (0.5 to 4 times the dose used to treat chagasic patients). Subsequent
      neurological examination revealed apathy, ataxia, spastic tetraplegia with
      hyperreflexia of stretching reflexes, balance disorders and asymmetrical gait.
      These alterations appeared earlier and were more intense at the higher doses.
      Drug withdrawal also left dose- and time-dependent sequelae like ataxia,
      hypertonia, hyperreflexia and alterations of balance. No peripheral neuropathy
      was detected. The present findings suggest that a careful reevaluation of the
      side effects of benznidazole in humans is necessary.

PMID- 9260854
TI  - Hyperbaric oxygen in the treatment of acute ischemic stroke: an unsettled issue.
AB  - Therapy for acute ischemic stroke can be approached in two basic ways: first, by
      an attempt to restore or improve blood flow in an occluded vascular territory
      and, second, via therapy directed at the cellular and metabolic targets. As local
      anoxia and energy failure are the initiating cellular stage in ischemia, the
      inhalation of oxygen at increased atmospheric pressures might be effective.
      Treatment of acute focal cerebral ischemia with hyperbaric oxygen (HBO) has been
      reported in animals and humans. In general, the results of research in animals
      have suggested a promising role for the use of HBO. More than 400 cases of human
      ischemic stroke treated with HBO have been reported. In about half of the cases,
      improvement in status has been claimed on clinical or electroencephalographic
      grounds. In fact, the effectiveness of HBO in most disease processes other than
      carbon monoxide poisoning and decompression sickness is a subject of major
      ongoing debate. This short review will attempt: (1) to recall some early
      experiments involving HBO in the treatment of acute ischemia: (2) to point out
      some conflicting results regarding the role of HBO on cellular and metabolic
      disorders; and (3) to determine the possibility of a future role for HBO therapy
      in acute ischemic stroke.

PMID- 9260853
TI  - Experimental benznidazole encephalopathy: II. Electroencephalographic and
      morphological alterations.
AB  - We describe electroencephalographic (EEG) and morphological alterations in the
      CNS of dogs treated with benznidazole. The relationship between dose, duration of
      treatment and intensity of lesions observed was examined and used to establish
      anatomo-clinical associations. Two predominant EEG patterns were noted in treated
      dogs. Most of the animals (Group I) that received acute treatment with high doses
      (30 mg/kg/day) for 15 days followed by treatment at a lower dose (10 mg/kg/day)
      exhibited a type 2, EEG pattern, i.e., low voltage desynchronized with fast
      activity (LVFA). In contrast, most of the animals (Group II) that received short
      term acute treatment with high doses (40 mg/kg/day) for 7 days followed by
      chronic treatment at lower doses (20 and 5 mg/kg/day) presented a type 1 EEG
      pattern. high voltage diffuse with slow activity (HVSA). Even after the drug was
      discontinued, the animals presented mild EEG alterations. These alterations.
      observed during and after treatment with benznidazole, suggest the presence of
      encephalopathy with multifocal characteristics. Several morphological alterations
      were observed in the animals, the most important being: lymphocytic inflammatory
      infiltrate, neuronal degeneration, satellitosis, demyelination and axonal
      degeneration, microglial proliferation, necrosis and gliosis. Such alterations
      involved the meninges, cerebral cortex, hemispheric white matter and subcortical
      gray matter, brain stem, cerebellum, and, less frequently, the spinal cord. No
      histopathological alterations were detected in the peripheral nerves. All
      encephalic levels were involved in all animals treated although the use of the
      high doses for 15 days (Group I) appeared to result in more lesions in the
      subcortical gray matter and the lower brainstem when compared to the use of high
      doses for 7 days (Group II) which led to greater involvement of the cerebral
      cortex, hemispheric white matter, cerebellum and medulla.

PMID- 9260855
TI  - Peripheral autonomic nerve dysfunction in asymptomatic leprosy contacts.
AB  - In endemic areas, subclinical autonomic nerve dysfunction may be a manifestation
      of infection with M. leprae and possibly allow detection before progression to
      clinical disease. Vasomotor reflex (VMR) testing was performed in 36 asymptomatic
      leprosy contacts (24 household contacts, 12 hospital contacts) and 47 age- and
      sex-matched controls in Pokhara, Nepal. Mean age was 30 years, two thirds were
      male. A Moor instruments DRT4 laser doppler monitor was used for velocimetry of
      microvascular blood flow. The flow reduction following an inspiratory gasp was
      recorded from finger and toe tips. Mean percent reduction was 57.8 (standard
      deviation 14.6) among household contacts, 61.9 (17.5) among hospital contacts and
      66.8 (7.8) among controls (p=0.001 by analysis of variance). The prevalence of
      abnormal test results was 54% among household contacts, 42% among hospital
      contacts and 15% among controls (p=0.0005 by chi-square test for trend).
      Subclinical autonomic neuropathy is common among healthy contacts of leprosy
      patients. Prospective studies are now needed to clarify to what extent abnormal
      VMR tests predict the risk of progression to clinical disease.

PMID- 9260856
TI  - Spectral analysis of heart rate and blood pressure in Guillain-Barre patients
      with respiratory failure.
AB  - The clinical value of heart rate and blood pressure variation (HRV and BPV)
      spectra was assessed in 11 consecutive patients with Guillain-Barre syndrome
      (GBS) on artificial ventilation. Their HRV and BPV spectra were compared with
      those from 28 control intensive care unit (ICU) patients without peripheral nerve
      disorders. ICU controls had low respiratory HRV during controlled ventilation. If
      present, it was closely related to, but smaller than BPV, suggesting baroreceptor
      reflex mediation. Respiratory HRV similar to that of healthy controls was
      observed only in ICU controls with significant spontaneous ventilation. HRV was
      prominent in a subgroup of GBS patients who suffered from bradycardia or sinus
      arrest, whereas GBS patients without episodic bradycardia only exceptionally had
      respiratory HRV. Interpretation of HRV during artificial ventilation cannot be
      extrapolated from experience with spontaneously breathing subjects. In contrast
      to diabetic neuropathy, not loss, but preservation of respiratory HRV was ominous
      in artificially ventilated GBS patients. A pattern of prominent broad respiratory
      HRV peaks and narrow BPV peaks occurred only in GBS and forebode sinus arrest.

PMID- 9260857
TI  - Simultaneous bilateral contrast transcranial doppler monitoring in patients with
      intracardiac and intrapulmonary shunts.
AB  - The prevalence of a right-to-left intracardiac shunt, demonstrated by
      echocardiography and transcranial Doppler sonography has been shown to be higher
      in stroke patients than in normal controls. The aim of this study was to assess
      the sensitivity and specificity of contrast transcranial Doppler sonography in
      comparison to transesophageal echocardiography in the detection and
      differentiation of intracardiac and intrapulmonary shunts and to correlate the
      transcranial Doppler findings with clinical outcome and morphological findings.
      Forty five consecutive stroke patients with suspected paradoxical embolism were
      entered into the study. In all 25 patients with middle cerebral artery stroke of
      the left (56%) or right (44%) territory and echocardiographic demonstrated patent
      foramen ovale (80%) or intrapulmonary shunt (20%), simultaneous bilateral
      transcranial Doppler sonography of the middle cerebral arteries was performed
      after contrast medium injection during rest and valsalva straining under
      standardized and optimized conditions. Overall sensitivity for the detection of a
      right-to-left shunt by contrast transcranial Doppler sonography was 97% and
      overall specificity was 70%. Bilateral appearance of microbubbles, microbubble
      count and time delay of microbubble appearance significantly increased after
      valsalva straining. In patients with intracardiac shunts, a significantly higher
      microbubble count (32 vs. 13 in patients with an intrapulmonary shunt) and a
      shorter time interval of microbubble appearance (11 vs. 14 s in patients with
      intrapulmonary shunts) was observed. There was no correlation between the side
      and numerical distribution of microbubble count and the location and severity of
      the current clinical symptoms, as well as between microbubble count and presence
      and hemispherical distribution of brain infarcts. Transcranial Doppler sonography
      is a highly sensitive method for the detection of right-to-left shunts, whether
      of cardiac or pulmonary location. However. no correlation was found between the
      side and number of microbubbles counted and the clinical symptomatology.

PMID- 9260858
TI  - Randomized trial of azathioprine or prednisone for initial immunosuppressive
      treatment of myasthenia gravis.
AB  - Ten patients with myasthenia gravis were randomized to azathioprine or prednisone
      as the initial immunomodulating drug and followed for over one year. Of five
      patients randomized to azathioprine, two had idiosyncratic reactions and were
      immediately crossed over to prednisone. Two patients completed one year on
      azathioprine with little or no change in level of function and were crossed over
      to prednisone and showed greater improvement. The fifth patient on azathioprine
      had a satisfactory improvement and continued on it during the second year. All
      patients initially randomized to prednisone improved, but the degree varied among
      patients. The side effects of azathioprine were idiosyncratic reactions. The side
      effects of prednisone were manageable.

PMID- 9260859
TI  - The geographic distribution of Parkinson's disease mortality in the United
      States.
AB  - PURPOSE: This study examines geographic variation in reporting of Parkinson's
      disease mortality in the U.S. METHODS: National Center for Health Statistics and
      Bureau of the Census data were used to map age-adjusted, race- and race-gender
      specific Parkinson's disease mortality rates in the U.S. for 1988. RESULTS: Among
      whites, high underlying-cause rates predominated in the North and low rates
      predominated in the South, whereas high contributing and all-cause rates were
      concentrated in the northeastern U.S. Strong north-to-south decreasing gradients
      were present for both underlying- and all-cause rates for whites, regardless of
      gender, whereas a clear west-to-east gradient could not be demonstrated.
      Geographic variation in contributing- and all-cause rates was partially explained
      by variation in tendency to report contributing causes of death. Reported rates
      among blacks were significantly lower than among whites. There was no latitudinal
      or longitudinal gradient of underlying-cause rates for blacks, but there was a
      relatively weak north-to-south decreasing gradient of all-cause rates for blacks,
      regardless of gender. CONCLUSIONS: The large-scale pattern of underlying-cause
      Parkinson's disease mortality among whites has persisted for over three decades.

PMID- 9260860
TI  - Opposite effects of L-arginine and nitroglycerin on cerebral blood velocity:
      nitric oxide precursors and cerebral blood velocity.
AB  - Nitric oxide (NO), a gaseous molecule synthesized in the arteriolar endothelium
      from the amino acid L-arginine (L-arg), has been identified as the previously
      described Endothelium-Derived Relaxing Factor (EDRF): nitroderivatives such as
      nitroglycerin are known to induce vasodilation via NO release. The aim of this
      study was to evaluate by Transcranial Doppler (TCD) monitoring any changes in
      cerebral hemodynamics induced by both the infusion of L-arg and the sublingual
      administration of nitroglycerin in 20 healthy subjects. L-arg infusion induced a
      significant increase in blood velocity compared to the baseline value (mean +/-
      S.D. percent change = 18 +/- 8.71; p<0.0001 ) and a slight but significant
      decrease in Pulsatility Index. By contrast, nitroglycerin was able to cause a
      significant decrease in blood velocity (mean +/- S.D. percent change = 24.8 +/-
      7.68; p<0.0001), while leaving Pulsatility Index unchanged. These data suggest
      that L-arg and nitroglycerin, both hypothesized to use NO as the final product at
      the vascular level, result in opposite blood velocity patterns within the
      cerebral circulation. This may be due to the particular type of artery and/or to
      the local endothelial environment whereby the released NO may act.

PMID- 9260861
TI  - Blood flow velocity changes in the middle cerebral artery as an index of the
      chronicity of hypertension.
AB  - This study was designed to demonstrate cerebral hemodynamic changes related to
      hypertension using transcranial Doppler ultrasonography. We measured the flow
      velocities and the Gosling pulsatility index of the middle cerebral artery and
      the internal carotid artery in 94 stroke-free, hypertensive patients and 81 age-
      and gender-matched healthy controls. Compared with the control subjects, patients
      with a longer duration (> or = 5 years) of hypertension showed significantly
      lower flow velocities of the middle cerebral artery and a higher Gosling
      pulsatility index of the middle cerebral- and the internal carotid artery. These
      differences were not observed in patients with a shorter duration of hypertension
      (<5 years). In the patient group, the mean velocity of the middle cerebral artery
      was significantly and inversely correlated with the duration of hypertension.
      Decreased flow velocity with increased pulsatility observed in this study suggest
      that alterations in the small cerebral vessels and arterioles contribute
      primarily to cerebral hemodynamic changes occurring in long-standing hypertension
      and also suggest the possible usefulness of transcranial Doppler in monitoring
      the progression of cerebral atherogenesis related to hypertension.

PMID- 9260862
TI  - Antibodies to fucogangliosides in neurological diseases.
AB  - We examined serum antibodies to 4 species of fucogangliosides: fucosyl-GM1,
      fucosyl-GD1b, alpha galactosyl (alpha fucosyl) GM1 and alpha galactosyl (alpha
      fucosyl) GD1b, in 329 patients with various neurologic diseases, 32 patients with
      non-neurologic autoimmune diseases and 50 healthy persons. Nine patients with
      Guillain-Barre syndrome, 2 with amyotrophic lateral sclerosis and 2 with cerebral
      infarction had IgG anti-fucosyl-GM1 antibody. Five patients with Guillain-Barre
      syndrome, 1 with cerebral infarction and 1 normal control subject had IgM anti
      fucosyl-GM1 antibody, 3 of whom also had IgG anti-fucosyl-GM1 antibody. Sixteen
      of 17 patients who had IgG or IgM antibody to fucosyl-GM1 showed no sensory
      dysfunction. Yoshino et al. [J. Neurochem. 1993, 61: 658-663] speculated that
      anti-fucosyl-GM1 antibody functions in the development of sensory neuropathy, but
      our results do not support this. Two patients with sensory ataxic neuropathy had
      high IgM antibody titers to fucosyl-GD1b and alpha galactosyl (alpha fucosyl)
      GD1b. These fucogangliosides may be the target molecules for serum antibodies in
      some patients with sensory ataxic neuropathy.

PMID- 9260863
TI  - Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke.

PMID- 9260864
TI  - Molecular mechanisms involved in the regulation of prostaglandin biosynthesis by
      glucocorticoids.
AB  - The anti-inflammatory properties of glucocorticoids are attributed in part, to
      their interference with prostaglandin synthesis. Phospholipases A2 and
      cyclooxygenases, the key enzymes of prostaglandin biosynthesis, are targets of
      glucocorticoid action; the molecular mechanisms, however, are not yet understood
      in detail. Obviously, glucocorticoids can act at different levels of gene
      regulation depending on cell type and inducing stimulus. The current knowledge of
      glucocorticoid interference with phospholipase A2 and cyclooxygenase expression
      is summarized. In comparison with other nonsteroidal anti-inflammatory drugs,
      glucocorticoids are unique inasmuch as they also inhibit cytokine synthesis and
      expression of other inflammation-related enzymes. Based on a more detailed
      understanding of glucocorticoid action, it may be possible to therapeutically
      exploit the anti-inflammatory effects and at the same time avoid the unwanted
      metabolic actions of these steroids.

PMID- 9260865
TI  - Altered in vivo toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in C-SRC
      deficient mice.
AB  - Administration of a single i.p. dose of 115 microg/kg of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) to homozygous and heterozygous c-src deficient
      mice (i.e. c-src -/- and -/+ mice) and their wild-type littermates (c-src +/+
      mice) induced differential toxic responses. In c-src +/+ mice, there were clear
      cut signs of the toxicity of TCDD, such as the loss of weight in the body, thymus
      and adipose tissue, whereas in c-src -/+ mice these effects were modest and were
      not statistically significant. Yet, hepatomegaly, a characteristic effect of
      TCDD, took place in all three strains of mice. Histological examination of liver
      samples from control mice and from mice treated with TCDD for 10 days showed that
      there are qualitative differences in the expression of the effects of TCDD
      between control and treated mice as well as between c-src -/+ and +/+ mice. In
      the case of c-src +/+ mice, the predominant lesions were lipid accumulation,
      glycogen depletion, edema formation and necrosis, as shown by the presence of
      large areas of ballooning degeneration, and cellular influx of fluid. These
      changes were demonstrated only marginally in c-src -/+ mice. The predominant
      effect in -/+ mice was edema formation. At a high dose of TCDD (345 microg/kg),
      all of the +/+ mice died within 34 days, whereas none of the c-src -/+ mice died.
      Together these results clearly indicate that some of the toxic effects of TCDD
      are not fully expressed in c-src deficient mice.

PMID- 9260866
TI  - Cutaneous exposure to bis-(2-chloroethyl)sulfide results in neutrophil
      infiltration and increased solubility of 180,000 Mr subepidermal collagens.
AB  - Exposure to bis-(2-chloroethyl)sulfide (BCES; "sulfur mustard") causes delayed
      formation of slowly healing skin blisters. Although the histopathology of BCES
      injury is well characterized [reviewed in Smith et al., J Am Acad Dermatol 32:
      767-776, 1995], little is known of the cutaneous toxicity at the molecular level.
      To identify biological markers of exposure, epidermal and subepidermal extracts
      were prepared from 48 individual hairless guinea pigs (HGP) at successive 3-hr
      intervals following exposure to BCES vapor, and compared using gel
      electrophoresis, and lectin- and antisera-binding. Inflammation was assessed by
      measuring edema and myeloperoxidase activity. Edema reached peak levels at 15-18
      hr and remained elevated above controls at 24 hr. Recruitment of neutrophils,
      deduced from increased myeloperoxidase, occurred as early as 3 hr after BCES
      exposure with maximum infiltration at 6-12 hr. Binding of concanavalin-A lectin
      revealed increased amounts, relative to contralateral control sites, of two
      approximately 180,000 Mr polypeptides in subepidermal protein extracts from the
      BCES-exposed skin obtained > or = 12 hr after exposure. This alteration was not
      found in epidermal protein extracts prepared from the same animals. Based upon
      the determined amino acid compositions, both polypeptides had significant
      collagenous triple helical content (>75%). They could be distinguished
      immunologically from collagen types I, III, and IV by using polyclonal antisera.
      We conclude that exposure of HGP skin to BCES results in an early neutrophil
      infiltration that precedes epidermal-dermal separation and selective alterations
      of the subepidermal extracellular matrix.

PMID- 9260868
TI  - Modulation of transferrin receptor expression by dexrazoxane (ICRF-187) via
      activation of iron regulatory protein.
AB  - Dexrazoxane (ICRF-187) has recently been demonstrated to reduce cardiac toxicity
      induced by chemotherapy with anthracyclines, although the reason for this
      phenomenon has remained obscure thus far. In order to investigate whether ICRF
      187 might exert its effects by modulating iron metabolism, we studied the drug's
      potential to influence the maintenance of iron homeostasis in two human cell
      lines. We demonstrate that ICRF-187 enhanced the binding affinity of iron
      regulatory protein (IRP), the central regulatory factor for posttranscriptional
      iron regulation, to RNA stem loop structures, called iron responsive elements
      (IRE), in THP-1 myelomonocytic as well as K562 erythroleukemic cells. Increased
      IRE/IRP interaction was paralleled by an elevation of transferrin receptor (trf
      rec) mRNA levels which, according to the well-established mechanism of
      posttranscriptional iron regulation, was likely due to stabilisation of trf-rec
      mRNA by IRP. Subsequently, ICRF-187 treatment of cells increased trf-rec surface
      expression and enhanced cellular iron uptake. All these events, i.e. IRP
      activation, stabilisation of trf-rec mRNA and increased surface expression of the
      protein in response to ICRF-187, follow a dose-response relationship. Increased
      cellular uptake and sequestration of iron in response to ICRF-187 may contribute
      to the protective activity of ICRF-187 by reducing the iron-anthracycline complex
      and iron-catalysed generation of hydroxyl radicals via the Haber-Weiss reaction.

PMID- 9260867
TI  - Cellular relocalisation of protein kinase C-theta caused by staurosporine and
      some of its analogues.
AB  - The microbial product staurosporine is a protein kinase C (PKC) inhibitor with
      some phorbol ester-agonistic properties. It is known to cause the translocation
      of the PKC isoenzymes epsilon and delta from the cellular cytosol to the membrane
      and nucleus. We tested the hypothesis that it also affects the cellular
      localisation of the novel PKC isoenzyme theta, and that staurosporine analogues,
      some of which are currently under clinical evaluation as potential anticancer
      drugs, have a similar effect. Their ability to alter PKC-theta distribution was
      studied in human-derived A549 lung carcinoma cells. Western blot analysis and
      confocal microscopy after indirect immunofluorescence staining showed that
      staurosporine (100 nM), like the phorbol ester 12-O-tetradecanoylphorhol-13
      acetate (25 nM) caused the translocation of PKC-theta from the cytosol to the
      membrane and the nucleus. The bisindolylmaleimide GF 109203X mimicked
      staurosporine, but had a weaker effect. Ro 31-8220 and UCN-01 decreased cytosolic
      PKC-theta only at 1 microM. CGP 41251 had no effect on PKC-theta in either
      experimental design. The results show that some, but not all, staurosporine
      analogues share the partial phorbol ester-agonistic PKC-translocatory activity of
      the parent molecule.

PMID- 9260869
TI  - Modulation of the hepatic expression of the estrogen-regulated mRNA stabilizing
      factor by estrogenic and antiestrogenic nonsteroidal xenobiotics.
AB  - Estrogen-mediated accumulation of apolipoprotein II (apoII) mRNA in the avian
      liver is due, in part, to its stabilization. This stabilization appears to be due
      to the estrogen-regulated mRNA stabilizing factor (E-RmRNASF) that is expressed
      in response to estrogen. The E-RmRNASF protects the mRNA from targeted
      endonucleolytic degradation (Ratnasabapathy, Cell Mol Biol Res 41: 583-594,
      1995). To determine whether certain environmental xenobiotics altered the
      expression of the gene encoding E-RmRNASF by mimicking estrogen, roosters were
      given estrogen, tamoxifen, clomiphene, hexachlorophene, lindane, rotenone,
      chlordecone, dichlorodiphenyltrichloroethane (DDT); Araclor, methoxychlor,
      dieldrin, toxaphene, or bisphenol-A parenterally. Uniformly radiolabeled, capped,
      and polyadenylated apoII mRNA, incubated in vitro in the presence of liver
      cytosolic extracts from birds that received estrogen, tamoxifen, hexachlorophene,
      chlordecone, or Araclor, remained stable, indicating that these agents were
      estrogenic and stimulated the expression of E-RmRNASF. However, the same mRNA was
      degraded in similar extracts from control roosters and those treated with
      clomiphene, DDT, methoxychlor, dieldrin, rotenone, toxaphene, lindane, or
      bisphenol-A. To determine whether the latter agents were antiestrogenic, roosters
      were given a 1:5 molar combination of estrogen and each of the xenobiotics. ApoII
      mRNA showed degradation in liver extracts from roosters that received clomiphene,
      toxaphene, or bisphenol-A, indicating that these agents prevented estrogenic
      stimulation of expression of the E-RmRNASF and were antiestrogenic. However, the
      rest of the xenobiotics failed to antagonize estrogenic stimulation of E-RmRNASF
      gene expression. These results set a precedent in showing the estrogenic and
      antiestrogenic effects in vivo of environmental xenobiotics on the expression of
      a regulatory protein involved in estrogen-mediated mRNA stabilization.

PMID- 9260870
TI  - Dihydro-1,4-benzothiazine-6,7-dione, the ultimate toxic metabolite of 4-S
      cysteaminylphenol and 4-S-cysteaminylcatechol.
AB  - 4-S-Cysteaminylphenol (4-S-CAP) and the corresponding catechol 4-S
      cysteaminylcatechol (4-S-CAC) have been evaluated for melanocytotoxicity. It was
      shown recently that tyrosinase oxidation of these substrates produces a violet
      pigment, dihydro-1,4-benzothiazine-6,7-dione (BQ). In this study we examined
      whether BQ is the ultimate toxic metabolite produced in melanoma cells from 4-S
      CAP/4-S-CAC. Biochemical experiments showed that (1) BQ was formed by
      autoxidation of 4-S-CAC as well as by tyrosinase oxidation of 4-S-CAP/4-S-CAC,
      (2) BQ reacted rapidly with thiols such as reduced glutathione (GSH), and (3) BQ
      inhibited the activity of alcohol dehydrogenase, an SH enzyme. In vitro
      experiments showed that (1) the cytotoxicity of 4-S-CAC was mostly prevented by
      catalase and superoxide dismutase, (2) BQ was highly cytotoxic to B16 melanoma
      cells (IC50 being 3.9 microM as compared with 507 microM for 4-S-CAP), (3) BQ was
      metabolized rapidly to a GSH adduct in melanoma cells, and (4) the same GSH
      adduct was also formed upon incubation of melanoma cells with 4-S-CAP, the
      reaction being tyrosinase dependent. In vivo experiments showed that intratumoral
      administration of BQ (0.5 micromol) inhibited the subcutaneous growth of B16
      melanoma nearly as effectively as 4-S-CAP/4-S-CAC (20 micromol). These results
      indicate that BQ is the ultimate toxic metabolite produced by tyrosinase
      oxidation of 4-S-CAP/4-S-CAC. BQ deprives melanoma cells of GSH and may
      inactivate SH enzymes essential for DNA synthesis and cell proliferation by
      covalent binding through their cysteine residues, thereby exerting
      melanocytotoxicity. Cytotoxicity of 4-S-CAC depends mostly on autoxidation
      producing BQ and active oxygens.

PMID- 9260871
TI  - Decreased binding and autophosphorylation of the epidermal growth factor receptor
      in ethanol-fed rats.
AB  - We have shown previously that binding and processing of epidermal growth factor
      are impaired in livers of ethanol-fed rats. In the current study, we examined
      these ethanol-induced alterations in greater detail by studying both high and low
      affinity epidermal growth factor binding as well as the ability of added ligand
      to stimulate receptor autophosphorylation. We also measured the binding of anti
      receptor antibody to intact and permeabilized cells in order to determine more
      accurately the levels of receptor protein. Hepatocytes were isolated from ethanol
      fed and pair-fed control rats. Ligand binding, antibody binding, and ligand
      induced receptor autrophosphorylation were measured in the respective cell
      populations. In ethanol-fed animals, binding to both high and low affinity states
      of the hepatic epidermal growth factor receptor was decreased by 40-50% (P <
      0.01). This ethanol-induced decrease in ligand binding was accompanied by a
      reduced ability of epidermal growth factor to stimulate receptor
      autophosphorylation (32% decrease, P < 0.01). In contrast, binding of anti
      receptor antibody was not altered in ethanol-fed animals. In conclusion, chronic
      ethanol feeding decreased epidermal growth factor binding with a concomitant
      decrease in the ability of the receptor tyrosine kinase to phosphorylate tyrosine
      residues. These changes were not accompanied by an actual decrease in receptor
      protein content. These findings could be relevant to modified responses to this
      growth factor in the livers of chronic ethanol-fed animals.

PMID- 9260872
TI  - Effect of prior morphine-3-glucuronide exposure on morphine disposition and
      antinociception.
AB  - Morphine-3-glucuronide (M3G), the primary metabolite of morphine in humans and
      rats, has been reported to antagonize morphine-induced pharmacologic effects. The
      present experiment was conducted to evaluate the effect of prior systemic M3G
      exposure on morphine disposition and antinociceptive response in male Sprague
      Dawley rats. Saline (N = 6), low dose M3G (0.15 mg/hr, N = 7), or high dose M3G
      (0.30 mg/hr, N = 6) was infused for 720 min prior to the administration of
      morphine by i.v. bolus (2 mg/kg). Tail-flick latencies in response to hot water
      (50 degrees) were assessed prior to and for 180 min after the morphine test dose.
      M3G exposure had no significant effect on morphine pharmacokinetics, although a
      disproportionate increase in M3G concentrations was observed following the
      morphine i.v. bolus dose in rats infused with high dose M3G. Morphine-induced
      antinociception, expressed as the percent of maximum response (%MPR), was maximum
      15 min after morphine administration and returned to baseline by 180 min. A
      pharmacokinetic-pharmacodynamic model was constructed to relate tail-flick
      latencies to morphine serum concentrations. In saline-exposed rats, the
      antinociceptive response to morphine was characterized by a sigmoidal Emax model,
      with an EC50 of 328 ng/mL, a Hill coefficient (gamma) of 4.5, and a half-life for
      the offset of pharmacologic effect of 11 min. No statistically significant
      differences in the intensity or duration of morphine-induced response were
      detected between saline- and M3G-exposed animals. These results suggest that
      systemic formation of M3G is unlikely to contribute significantly to the
      development of tolerance to morphine antinociception.

PMID- 9260873
TI  - Differences in the hydrolysis of enkephalin congeners by the two domains of
      angiotensin converting enzyme.
AB  - The hydrolysis of enkephalin (Enk) congeners by the isolated N- (N-ACE) and C
      domain of angiotensin I converting enzyme (ACE) and by the two-domain somatic ACE
      was investigated. Both Leu5- and Met5-Enk were cleaved faster by the C-domain
      than by N-ACE; rates with somatic ACE were 1600 and 2500 nmol/min/nmol enzyme
      with both active sites being involved. Substitution of Gly2 by D-Ala2 reduced the
      rate to 1/3rd to 1/7th of that of the Enks. N-ACE cleaved Met5-Enk-Arg6-Phe7
      faster than the C-domain, probably with the highest turnover number of any
      naturally occurring ACE substrate (7600 min(-1)). This heptapeptide is also
      hydrolyzed in the absence of Cl-, but the activation by Cl- is unique; Cl-
      enhances the hydrolysis of the heptapeptide by N-ACE but inhibits it by the C
      domain, yielding about a 5-fold difference in the turnover number at
      physiological pH. This difference may result in the predominant role of the N
      domain in converting Met5-Enk-Arg6-Phe7 to Enk in vivo.

PMID- 9260874
TI  - Transformed and immortalized cellular uptake of oligodeoxynucleoside
      phosphorothioates, 3'-alkylamino oligodeoxynucleotides, 2'-O-methyl
      oligoribonucleotides, oligodeoxynucleoside methylphosphonates, and peptide
      nucleic acids.
AB  - Direct quantitative comparisons of cellular uptake across a wide variety of
      analogs and cell types are necessary for the design of oligonucleotide diagnostic
      and therapeutic applications. This work reports quantitative cellular uptake and
      nuclear localization of [14C]oligodeoxynucleoside phosphorothioates (PS), 3'
      alkylamino oligodeoxynucleoside phosphodiesters (PO-NH2), 2'-O-methyl
      oligoribonucleoside phosphodiesters (2OM), peptide nucleic acids (PNA), and
      oligodeoxynucleoside methylphosphonates (MP) in several transformed or
      immortalized cell lines. All analogs demonstrated active cellular uptake in that
      intracellular concentrations greatly exceeded the extracellular 1 microM
      concentration within 1-3 hr. However, by 9-24 hr, cellular accumulations of PS
      exceeded those of PO-NH2 and 2OM by 3- to 5-fold, PNA by 6- to 7-fold, and MP by
      8- to 10-fold. Similar results were observed in two transformed cell lines, HL-60
      leukocytes and H-ras transformed fibroblasts, using three different heterogeneous
      sequences. H-ras and IGF-1R transformed fibroblasts had a 2- to 5-fold higher
      uptake of all analogs than non-transformed immortalized fibroblasts. Nuclear
      levels of the PO-NH2, PS, and MP analogs were approximately 25% of total cellular
      uptake, while nuclear percentages of 2OM and PNA were less than 20%, suggesting
      some differences in nuclear localization among the analogs. These observations
      provide a direct quantitative comparison of cellular uptake as a function of
      oligonucleotide modification, and imply that transformation enhances cellular
      uptake. From the perspective of therapy and diagnosis, clear trade-offs were
      apparent between efficiency of uptake on the one hand, and nuclease resistance
      and hybridization strength on the other.

PMID- 9260875
TI  - Inhibition of protein kinase A and cyclic AMP response element (CRE)-specific
      transcription factor binding by delta9-tetrahydrocannabinol (delta9-THC): a
      putative mechanism of cannabinoid-induced immune modulation.
AB  - Delta9-Tetrahydrocannabinol (delta9-THC) binding to cannabinoid receptors induces
      an inhibition in adenylate cyclase activity through the engagement of a pertussis
      toxin-sensitive GTP-binding protein. In this study we investigated the
      ramifications of decreased cyclic AMP (cAMP) formation by delta9-THC on signaling
      events through the cAMP pathway distal to adenylate cyclase in mouse splenocytes.
      Delta9-THC treatment produced a marked and concentration-related decrease in
      forskolin-inducible protein kinase A (PKA) activity. This decrease in kinase
      activity was due to an inhibition in cAMP formation and not through a direct
      effect on the kinase as evidenced by the fact that PKA activity could not be
      modulated directly by delta9-THC in the presence of exogenous cAMP. One of the
      primary roles of PKA in this signaling pathway is to activate transcription
      factors for subsequent binding to cAMP response elements (CRE) present in the
      promoter region of cAMP-responsive genes. In the present studies, we observed
      that forskolin treatment of splenocytes resulted in a rapid activation of trans
      acting factor binding to the CRE, which peaked at 30-60 min and whose binding was
      repressed concentration dependently in the presence of delta9-THC. As with
      forskolin, mitogenic stimulation including anti-CD3 mAb or phorbol ester plus
      ionomycin treatment of splenocytes induced CRE binding activity, which was
      maximal around 60 min and was suppressed by delta9-THC treatment. In conclusion,
      these data indicate that cAMP-mediated signal transduction is inhibited by delta9
      THC and consequently leads to a decrease in the activation of transcription
      factors that bind to CRE regulatory sites.

PMID- 9260876
TI  - Effect of 2',3'-dideoxycytidine on oxidative phosphorylation in the PC12 cell, a
      neuronal model.
AB  - Peripheral neuropathy induced by 2',3'-dideoxycytidine (ddC) could result from
      the previously shown inhibition of mtDNA replication by the action of ddC on the
      mitochondrial enzyme DNA polymerase gamma. Such inhibition would be expected to
      impair oxidative phosphorylation, and this was demonstrated in the present study
      for the PC12 cell, a model of a peripheral neuron. The dramatic rise in lactate
      formation upon exposure of the cell to ddC indicated that increased glycolysis
      was needed to produce ATP. A concomitant rise in O2 uptake indicated that
      oxidative phosphorylation had become uncoupled. When tested in a standard
      respiratory control system (isolated rat liver mitochondria), however, we found
      ddC not to be an uncoupler. Rather, the uncoupling most likely resulted from the
      failure of synthesis of one or more mitochondrial gene products necessary for
      oxidative phosphorylation. We also observed an important distinction between the
      manner in which ddC and 3'-azido-3'-deoxythymidine (AZT) act. ddC-exerted
      inhibition of oxidative phosphorylation was delayed for several days. This is
      consistent with the inhibition occurring indirectly, most likely as a result of
      the prior destruction of the mitochondrial genome, which encodes many of the
      components of the oxidative phosphorylation system. In contrast, we have shown
      previously that although AZT also impairs replication of the mitochondrial genome
      (in the Friend murine erythroleukemic cell), it also attacks directly an
      additional primary target leading to impairment of oxidative phosphorylation; its
      initial inhibition of this process is immediate, not occurring via inhibition of
      mitochondrial DNA replication.

PMID- 9260877
TI  - The multidrug-resistant human lung tumour cell line, DLKP-A10, expresses novel
      drug accumulation and sequestration systems.
AB  - Drug accumulation studies with the anticancer agents adriamycin and vincristine
      were carried out on the MDR variant of the human lung cell lines DLKP, DLKP-A10
      which overexpresses the MDR associated P-glycoprotein efflux pump. Reduced
      cellular accumulation of both agents was observed in the resistant variant. The
      subsequent addition of verapamil and cyclosporin A resulted in partial
      restoration of cellular accumulation of both drugs in the DLKP-A10 resistant
      variant while complete restoration of cellular drug levels was observed in the
      SKMES-1/ADR cell line. These results suggested that the accumulation defect
      observed in the SKMES-1/ADR cell line was P-glycoprotein mediated and that
      accordingly, the cells exhibited characteristics consistent with the classical
      MDR phenotype. In contrast, while P-glycoprotein also appears to mediate a
      reduction in cellular drug accumulation in the DLKP-A10 cells, an alternative
      transport mechanism may also be present. No significant increase in the
      expression of either the MRP or LRP transport proteins was observed in the
      resistant cells. Metabolic inhibition by antimycin A (but not sodium azide or 2
      deoxy-D-glucose) resulted in complete restoration of drug accumulation suggesting
      the presence of an alternative energy dependent transport mechanism. Fluorescent
      microscopy studies indicated different cellular localisation of the drug within
      the parental and resistant cells despite equivalent intracellular concentrations.
      These studies also revealed the presence of an ATP-dependent, vesicular
      sequestration mechanism which may be involved in the reduction of nuclear
      adriamycin accumulation in the DLKP-A10 cell line. This was indicated by
      observation of the disruption of cytoplasmic vesicles by antimycin A and also
      inhibition of cytoplasmic drug sequestration by the carboxylic ionophores,
      monensin and nigericin, accompanied by increased adriamycin accumulation and
      redistribution of the drug from the cytoplasm to the nucleus.

PMID- 9260878
TI  - Inhibition of N-formylmethionyl-leucyl-phenylalanine-stimulated tyrosine
      phosphorylation and phospholipase D activation by quercetin in rabbit
      neutrophils.
AB  - We investigated the effect of bioflavonoid quercetin on tyrosine phosphorylation
      and phospholipase D (PLD, EC 3.1.4.4) activation in rabbit peritoneal neutrophils
      stimulated by N-formylmethionyl-leucyl-phenylalanine (fMLP). The quercetin dose
      dependently inhibited degranulation and superoxide production in fMLP-stimulated
      neutrophils. A strong inhibitory effect of quercetin on the tyrosine
      phosphorylation of several proteins (40, 42, 43, 45, 46 and 75 kDa) was observed
      when the neutrophils were pretreated with different concentrations of quercetin.
      Furthermore, quercetin inhibited mitogen activated protein kinase (MAP kinase)
      and PLD activation induced by fMLP in a dose-dependent manner. The reduction in
      PLD activity was 30% at 0.1 microM and 70% at 100 microM of quercetin. These
      results suggest that impairment of neutrophil functions by quercetin may be due,
      at least in part, to inhibition of tyrosine phosphorylation and PLD activation.

PMID- 9260879
TI  - Effect of adenosine analogues on the expression of matrix metalloproteinases and
      their inhibitors from human dermal fibroblasts.
AB  - The effect of the cytostatic and antiviral adenosine analogues 3-deazaadenosine
      (c3Ado) and 3-deaza-(+/-)-aristeromycin (c3Ari) on human skin fibroblasts was
      studied. Variables examined were cell morphology, viability, DNA fragmentation,
      expression of matrix metalloproteinases (MMPs) and matrix metalloproteinase
      inhibitors (TIMPs). None of these variables were changed when cells were exposed
      to c3Ari concentrations ranging from 10(-5) to 10(-3) M or 10(-5) M c3Ado.
      However, large changes in cell morphology, viability and expression of MMPs and
      MMP inhibitors occurred when fibroblasts were treated with 10(-4) or 10(-3) M
      c3Ado. Cells rounded up, shrank in volume, some detached and viability was lost
      without any detectable fragmentation of DNA. These changes in morphology and
      viability were associated with a differentiated expression of MMPs and MMP
      inhibitors. A large increase in collagenase activity occurred, and depending on
      the concentration of the adenosine analogue and the length of treatment, this
      change in activity could be shown to be due to one or a combination of the
      following factors: an increased synthesis of the collagenase protein, a decreased
      production of TIMP-1 or an increased activity of the collagenase superactivator,
      stromelysin. In contrast to this, treatment with c3Ado resulted in a decreased
      gelatinase activity, which in part could be attributed to an increased production
      of an inhibitor that seemed to affect gelatinase but not collagenase. The
      cellular changes induced by c3Ado seemed to reflect some of the alteration in the
      metabolic machinery that appears during a drug-induced or programmed/controlled
      death of a dermal cell. The different effects exerted by these two adenosine
      analogues on dermal fibroblasts can at least in part explain why c3Ado have
      previously been shown to be more toxic than c3Ari in animal models.

PMID- 9260880
TI  - Tricyclic antidepressant-induced lipidosis in human peripheral monocytes in
      vitro, as well as in a monocyte-derived cell line, as monitored by
      spectrofluorimetry and flow cytometry after staining with Nile red.
AB  - Human mono- and lymphocytes from peripheral blood and the monoblastoid cell line
      U-937 were used in this in vitro study of drug-induced lipidosis. Mono- and
      lymphocytes were exposed for 4 days to three different tricyclic antidepressants
      (TCAs), imipramine (25 microM), clomipramine (10 microM) and citalopram (80
      microM). The lipophilic fluorophore Nile red, which stains intracellular lipid
      structures selectively, was used as a lipid probe. Fluorescence microscopy,
      spectrofluorimetry and flow cytometry were used to detect cellular lipidosis, as
      verified by electron microscopy. Our results demonstrate that imipramine,
      clomipramine and citalopram induce lipidosis in monocytes and U-937 cells, but
      not in lymphocytes. An accurate quantitation of induced intracellular lipidosis
      can be achieved by spectrofluorimetric and flow cytometric analysis.

PMID- 9260881
TI  - Effect of membrane-permeable sulfhydryl reagents and depletion of glutathione on
      calcium mobilisation in human platelets.
AB  - Exposure to peroxides is known to increase the sensitivity of platelets towards
      activation by agonists. Similar platelet-activating effects are induced by
      sulfhydryl reagents that evoke Ca2+-induced Ca2+ release (CICR) by stimulating
      the Ca2+-releasing property of the inositol-1,4,5-trisphosphate receptor. We
      questioned whether these compounds may act by mobilising intracellular calcium in
      platelets by altering the intracellular glutathione redox state. Using FURA2
      loaded, aspirin-treated platelets, Ca2+ signals were studied following exposure
      to the membrane-permeable sulfhydryl reagents, thimerosal and disulfiram, the
      glutathione peroxidase substrate, tert-butyl hydroperoxide, and the inhibitor of
      glutathione reductase, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). In single
      platelets monitored by fluorescence imaging techniques, thimerosal and disulfiram
      elicited repetitive spiking in [Ca2+]i after variable lag times, indicating that
      these compounds stimulated CICR. BCNU caused [Ca2+]i spiking of only low
      amplitude, whereas tert-butyl hydroperoxide was inactive. In platelets in
      suspension devoid of extracellular CaCl2, the sulfhydryl reagents, at
      concentrations which decreased glutathione by 25%, strongly increased the Ca2+
      responses of agonists that stimulated phospholipase C (thrombin) or acted
      independently of phospholipase C stimulation (thapsigargin). However, Ca2+
      release was only slightly promoted by concentrations of BCNU that resulted in
      substantial depletion of the glutathione level. Tert-butyl hydroperoxide was
      without effect on glutathione, but partially inhibited Ca2+ mobilisation with
      these agonists. It is concluded that, in platelets, the potent CICR-promoting
      effects of sulfhydryl reagents are not solely due to their reaction with
      intracellular glutathione, but that extensive reduction in glutathione content is
      associated with Ca2+ mobilisation and CICR.

PMID- 9260882
TI  - Induction of mitochondrial dysfunction and apoptosis in HeLa cells by bis
      pyridinium oximes, a newly synthesized family of lipophilic biscations.
AB  - When tested on HeLa cells, bis-pyridinium oximes (BPO), a family of newly
      synthesized molecules whose charged pyridinium moieties are linked by a linear
      polymethylene chain of variable length (N = 3 to 12) have been shown to possess
      an inhibitory effect on cell growth and finally to provoke cell death. BPO
      affected cells displayed reduced mitochondrial oxygen consumption and ATP stores
      and were blocked in the G1 phase of the cell cycle. Mitochondrial membrane
      potential, as assayed with the dye 3,3'-diexyloxacarbocyanine iodide [DiOC6(3)],
      increased in BPO-treated cells with time of exposure. Cell growth inhibition as
      well mitochondrial dysfunction were observed only with derivatives having a long
      polymethylene linking chain (N > or = 6). Furthermore, the concentration of the
      compound eliciting such effects was inversely related to the number of methylene
      groups in the linking chain. None of the BPO with N = 6 to 12 modified the
      mitochondrial DNA content, relative to the nuclear DNA content. In BPO (N = 8 and
      N = 12)-treated cells, chromatin fragmentation and internucleosomal DNA cleavage
      occurred massively, indicating that the death mode induced by these compounds is
      apoptosis. The possible pathway of action and the potential pharmacological
      interest of these compounds are discussed.

PMID- 9260883
TI  - Stimulation of gap junctional intercellular communication by thalidomide and
      thalidomide analogs in human skin fibroblasts.
AB  - It has been speculated that gap junctional intercellular communication (GJIC), an
      intercellular signalling pathway, is involved in embryogenesis by coupling
      compartments of the same developmental potential. We found that thalidomide
      induces GJIC in human fibroblasts after activation by liver microsomes in
      concentrations as low as 10(-7) M. Treatment of cells with the thalidomide analog
      EM-12 increased GJIC without prior activation. No alteration of GJIC was detected
      with phthalimide and glutamate, the components of thalidomide. However, 2
      phthalimido glutaric acid (PGA), a hydrolysis product of thalidomide, stimulated
      GJIC without activation at concentrations between 10(-10) M and 10(-5) M. We
      suggest modification of GJIC as a biochemical mechanism responsible for
      pharmacological and toxicological properties of thalidomide and related
      compounds.

PMID- 9260884
TI  - Effect of DNA on the inactivation of O6-alkylguanine-DNA alkyltransferase by 9
      substituted O6-benzylguanine derivatives.
AB  - Studies were carried out on the inactivation of pure human O6-alkylguanine-DNA
      alkyltransferase by 9-substituted O6-benzylguanine derivatives in the presence
      and absence of DNA. The addition of DNA increased the rate of inactivation of the
      alkyltransferase by O6-benzylguanine and its 9-methyl derivative but had little
      effect on the rate of inactivation by the 9-cyanomethyl derivative. In contrast,
      when O6-benzylguanine derivatives with larger 9-substituents such as ribose, 2'
      deoxyribose, dihydrotestosterone, or 2-hydroxy-3-(isopropoxy)propyl were used,
      the addition of DNA was strongly inhibitory to the inactivation. In the case of
      O6-benzylguanine, O6-benzylguanosine, and O6-benzyl-2'-deoxyguanosine, these
      results were confirmed by directly measuring the rate of formation by the
      alkyltransferase of guanine, guanosine, or 2'-deoxyguanosine, respectively. The
      data indicated that the presence of DNA activated the alkyltransferase, rendering
      it more reactive with O6-benzylguanine or O6-benzyl-9-methylguanine, but that DNA
      interferes with the binding of inhibitors with larger 9-substituents, presumably
      by competing for the same binding site. Since these inactivators readily
      inactivate alkyltransferase in cells, the amount of cellular alkyltransferase
      bound to DNA must be small or readily exchangeable with the free form.

PMID- 9260885
TI  - Dissociation between beta-adrenoceptor-mediated cyclic AMP accumulation and
      inhibition of histamine-stimulated phosphoinositide metabolism in airways smooth
      muscle.
AB  - Spasmogen-stimulated phosphoinositide hydrolysis represents one of the major
      signalling pathways mediating pharmacomechanical coupling in airways smooth
      muscle (ASM), and cyclic AMP-induced inhibition of phosphoinositidase C has been
      proposed as an important mechanism underlying the bronchodilator properties of
      beta2-adrenoceptor agonists. To examine this hypothesis in more detail we have
      undertaken a direct comparison of the effects of salbutamol and salmeterol, short
      and long-acting beta2-adrenoceptor agonists respectively, on cyclic AMP
      accumulation and histamine-stimulated [3H]-inositol phospholipid hydrolysis in
      bovine tracheal smooth muscle (BTSM) slices. Although salmeterol displayed a
      similarly greater potency over salbutamol for both stimulation of cyclic AMP, and
      inhibition of [3H]-inositol phosphate accumulation, there was a clear disparity
      between these agents with respect to both their efficacies and the duration of
      their effects. Hence while salmeterol caused a more protracted, but initially
      smaller increase in cyclic AMP accumulation compared to salbutamol, the
      inhibition of histamine-stimulated [3H]-inositol phosphate accumulation observed
      with salmeterol was of identical duration to salbutamol and was more marked than
      that of salbutamol at early time points. These data suggest that cyclic AMP
      accumulation is not the sole mechanism responsible for beta2-adrenoceptor-induced
      inhibition of phosphoinositide turnover in BTSM, and would support a recent
      proposal that cyclic AMP-dependent inhibition of agonist-stimulated Ca2+
      mobilization in ASM may be mediated by factors independent of inositol phosphate
      generation.

PMID- 9260886
TI  - The transition from proliferation to differentiation in nerve cells: what can we
      learn from muscle?

PMID- 9260887
TI  - Cloning and some novel characteristics of mitochondrial Hsp70 from Chinese
      hamster cells.
AB  - The cDNA for Chinese hamster mitochondrial Hsp70 (mHsp70) was cloned and
      sequenced using a polymerase chain reaction probe based on conserved regions in
      the Hsp70 family of proteins. The encoded protein consists of 679 amino acids
      which includes a N-terminal mitochondrial targeting sequence of 46 amino acids.
      The mHsp70 protein contains several sequence signatures that are characteristics
      of prokaryotic and eukaryotic organellar Hsp70 homologs. In a phylogenetic tree
      based on Hsp70 sequences, it branches with the gram-negative proteobacteria,
      supporting the endosymbiotic origin of mitochondria from this group of
      prokaryotes. The mHsp70 cDNA was transcribed and translated in vitro and its
      import into isolated rat heart mitochondria was examined. The precursor mHsp70
      was converted into a mature form of lower molecular mass (approximately 71 kDa)
      which became resistant to trypsin digestion. The import of mHsp70 into
      mitochondria was not observed in the presence of an uncoupler of energy
      metabolism or when the N-terminal presequence was lacking. The cDNA for mHsp70
      was expressed in Escherichia coli and a polyclonal antibody to the purified
      recombinant protein was raised. The antibody shows no cross-reactivity to
      recombinant cytosolic Hsp70 protein and in 2-D gel blots it reacted specifically
      with the mHsp70 protein only. In immunofluorescence experiments, the antibody
      predominantly labeled mitochondria, and the observed labeling pattern was
      identical to that seen with a monoclonal antibody to the mitochondrial Hsp60
      chaperonin. The affinity-purified antibody to mHsp70 was also employed to examine
      the subcellular distribution of the protein by cryoelectron microscopy and the
      immunogold-labeling technique. In these experiments, in addition to mitochondria,
      labeling with mitochondrial Hsp70 antibody was also observed on the plasma
      membrane and in unidentified cytoplasmic vesicles and granules. These studies
      raise the possibility that similar to the Hsp60 chaperonin and a number of other
      mitochondrial proteins, mHsp70 may have an extramitochondrial role.

PMID- 9260888
TI  - Internalized plasma membrane cholesterol passes through an endosome compartment
      that is distinct from the acid vesicle-lysosome compartment.
AB  - Cholesterol from the plasma membrane of MA-10 Leydig tumor cells is internalized
      into the cell and either esterified or used as substrate for steroid hormone
      synthesis. In the present studies we show that chloroquine and sphinganine cause
      LDL cholesterol and cholesteryl esters to accumulate in the cells. A lysosome
      fraction contained the excess cholesterol and cholesteryl esters. Both inhibitors
      blocked the conversion of plasma membrane cholesterol into intracellular
      cholesteryl esters and caused dose-dependent inhibition of dibutyryl-cAMP
      stimulated progesterone synthesis. Radiolabeled cholesterol applied to the plasma
      membrane of MA-10 cells accumulated in the lysosome fraction of chloroquine and
      sphinganine-treated cells. Evidence that these inhibitors did not require the
      Golgi was provided by experiments using brefeldin A. Experiments utilizing a
      fluorescent cholesterol analogue and a lysosomal marker indicated that
      cholesterol entered the cells in structures that were different than the acidic
      vesicle-lysosome compartment. Consistent with this observation was the
      observation that the peak fluorescence fractions of cells subjected to density
      gradient centrifugation was of lower density than the lysosome fraction.

PMID- 9260889
TI  - Radiation response of connexin43-transfected cells in relation to the "contact
      effect".
AB  - Some cell lines grown for only two cell doublings as multicell spheroids develop
      a form of resistance to killing by ionizing radiation that has been called the
      "contact" effect. While our previous results have implicated a role for higher
      order chromatin structure in the contact effect, another possible explanation is
      the presence of intercellular gap junctions that might facilitate communication
      between cells grown as spheroids and thereby enhance the ability of cells to
      resist or recover from radiation damage. To examine the role of gap junctions in
      the contact effect, rat glioma C6 and mouse EMT6 cell lines were transfected with
      a gene encoding the gap junctional protein connexin43. While C6 glioma cells are
      deficient in gap junctional communication, cells from spheroids were nonetheless
      more resistant than monolayers to killing by ionizing radiation, and the contact
      effect was present to a similar extent in the three transfected clones. For mouse
      EMT6 cells, radiosensitivity was similar whether cells were grown as monolayers
      or spheroids. Transfection of EMT6 cells with connexin43 increased gap junctional
      communication but did not promote development of a contact effect. Tumor volume
      doubling time in SCID mice increased significantly for one transfected clone;
      however, doubling time in vitro was also increased relative to the EMT6 parent.
      We conclude that extensive gap junctional communication is not a requirement for
      the increased radiation resistance observed when some cell lines are grown as
      spheroids.

PMID- 9260890
TI  - Induction of neurite outgrowth in PC12 cells by gamma-lactam-related compounds
      via Ras-MAP kinase signaling pathway independent mechanism.
AB  - Rat pheochromocytoma cells, PC12 cells, undergo differentiation in response to
      nerve growth factor (NGF). Although the Ras-MAP kinase signaling pathway has been
      shown to play a central role in the response to NGF, the precise mechanism which
      induces differentiation remains unclarified. Recently, several gamma-lactam
      related microbial products were identified to induce neurite outgrowth in
      neuroblastoma cells. Therefore, we synthesized a series of gamma-lactam-related
      compounds and tested for their ability to induce neurite outgrowth in PC12 cells.
      We found that two compounds, MT-19 and MT-20, induced neurite outgrowth at
      concentrations as low as 1 microg/ml. MT-19 and MT-20 have an n-hexadecyl group
      and an n-dodecyl group, respectively, at the position N-1 of the gamma-lactam
      ring, and the modification of this group leads to partial or complete loss of
      activity. In addition, the modification of the methyl and hydroxyl group at C-5
      leads to complete loss of activity, indicating a strict structure-activity
      relationship. Interestingly, MT-19 and MT-20 induced neurite outgrowth of PC12
      cells which lack normal Ras function. Furthermore, these compounds did not induce
      MAP kinase activation, suggesting that MT-19 and MT-20 do not require the Ras-MAP
      kinase signaling pathway which is shown to be necessary and sufficient for NGF
      induced neurite outgrowth. Consistent with this, none of the early- or late
      response genes tested, which include fos, zif268, Nur77, vgf, and transin, was
      induced. However, the protein level of three neurofilaments was increased after
      the incubation with these compounds. Since the level of other cytoskeleton
      proteins including actin and tubulin remained constant, MT-19 and MT-20
      specifically affected neurofilament synthesis and/or turnover. Taken together,
      these findings indicate that MT-19 and MT-20 induce neurite outgrowth by
      activating the downstream target of MAP kinase or by a novel mechanism which is
      distinct from the NGF-activated pathway.

PMID- 9260891
TI  - Protein kinase C is required for induction of 2',5'-oligoadenylate synthetases.
AB  - Induction of the p40/46 and p69/71 isoforms of the 2',5'-oligoadenylate (2-5A)
      synthetase by interferon-alpha (IFN-alpha) is variable among six different
      Burkitt lymphoma cell lines with Ramos cells expressing among the highest levels
      of these enzymes. Inhibitors of protein kinase C (PKC) block induction of mRNAs
      encoding both isoforms; however, induction of the p69/71 isoform is more
      sensitive to these inhibitors. Down-regulation of PKC by prolonged treatment with
      12-O-tetradecanoylphorbol-13-acetate (TPA) also blocks induction of 2-5A
      synthetase mRNAs and decreases both constitutive and IFN-alpha-induced enzymatic
      activity. Cotreatment of cells with TPA and IFN-alpha increases induction of 2-5A
      synthetase mRNAs above that seen in cells treated with IFN-alpha alone. IFN-alpha
      does not directly activate PKC-alpha or PKC-delta, the two most abundant PKC
      isoforms present in Ramos cells, suggesting that PKC activation by another
      signaling pathway is necessary for maximal induction of 2-5A synthetases by IFN
      alpha.

PMID- 9260892
TI  - Characterization of influenza virus-induced death of J774.1 macrophages.
AB  - The mechanism and role of influenza virus (IV)-induced pathogenesis of
      macrophages during respiratory infection are ill defined. Reported here are
      findings on IV-induced cytopathic effects (CPEs) for an in vitro experimental
      system using the murine macrophage cell line J774.1. CPE was elicited by 0.2 or
      greater multiplicity of infection (m.o.i.). CPEs showed a lag of 6-8 h
      postinfection and occurred most rapidly between 6 and 12 h. J774.1 cells did not
      support productive IV replication, but immunofluorescence demonstrated that IV
      protein synthesis occurred. Light microscopy and DNA staining showed that after
      death cells had very condensed cytoplasm and nuclei. Cell remnants were
      surrounded by intact plasma membrane (PM) as demonstrated by exclusion of a
      membrane-impermeant dye. Time-lapse video microscopy recordings between 6 and 10
      h postinfection showed sequential structural changes, including previously
      undescribed events. Notable changes were a rapid cytokinesis (zeiosis; "cell
      boiling"), followed by nuclear shrinkage, and an unusual transient blebbing of
      the PM. DNA fragmentation occurred after 12 h, producing a wide size range. UV
      inactivated virus failed to induce CPEs, and CPE was blocked by amantadine. N
      Acetylcysteine and pyrrolidine dithiocarbamate, but not other inhibitors of
      reactive oxygen intermediates, reduced or blocked the CPE. Most changes observed
      are those attributed to apoptotic processes rather than necrotic cell death. The
      kinetics and inhibitor effects suggest that IV infection and replication must be
      initiated to activate CPEs.

PMID- 9260893
TI  - An RXR-selective analog attenuates the RAR alpha-selective analog-induced
      differentiation and non-G1-restricted growth arrest of NB4 cells.
AB  - NB4, a human acute promyelocytic leukemia cell line expressing the promyelocyte
      retinoic acid receptor alpha (PML-RAR alpha) hybrid protein was treated with RAR-
      and retinoid X receptor (RXR)-selective analogs to determine their effects on
      cell proliferation, retinoblastoma (RB) tumor-suppressor protein phosphorylation,
      and differentiation. An RAR- or just RAR alpha-selective analog alone induced
      similar cell population growth arrest, cell cycle arrest without restriction to
      G1, hypophosphorylation of RB, and myelomonocytic cell surface differentiation
      marker expression (CD11b). In addition, an RAR alpha antagonist could inhibit the
      effects of the RAR alpha agonist completely. The RAR alpha-selective analog
      elicited response was attenuated by simultaneous addition of various RXR
      selective analogs. In contrast, each of the RXR-selective analogs was unable to
      induce any of the cellular responses analyzed. The growth arrest of NB4 cells is
      not G1-restricted and occurs at all points in the cell cycle. Cells growth
      arrested by treatment with an RAR alpha-selective analog show primarily
      hypophosphorylated RB. When these cells are sorted into G1 or S + G2/M
      subpopulations by flow cytometry, hypophosphorylated RB protein was in G1 as well
      as S + G2/M cells. This suggests that the hypophosphorylated RB protein may be
      mediating the growth arrest of NB4 cells at all points in the cell cycle. These
      results are consistent with an involvement of PML-RAR alpha and/or RAR alpha in
      the transduction of the retinoid signal in NB4 cells.

PMID- 9260894
TI  - Inhibition of mouse thymidylate synthase promoter activity by the wild-type p53
      tumor suppressor protein.
AB  - The p53 tumor suppressor protein is an important negative regulator of the G1 to
      S transition in mammalian cells. We have investigated the effect of p53 on the
      expression of the mouse thymidylate synthase (TS) gene, which normally increases
      as cells enter S phase. A luciferase indicator gene that was driven by the wild
      type or various modified forms of the TATA-less mouse TS promoter was transiently
      cotransfected with a p53 expression plasmid into TS-deficient hamster V79 cells
      and the level of luciferase activity was determined. We found that wild-type p53
      inhibited TS promoter activity by greater than 95% but had a strong stimulatory
      effect on an artificial promoter that contained multiple p53-binding sites. In
      contrast, an expression plasmid that encodes a mutant form of p53 or a wild-type
      retinoblastoma tumor suppressor protein had little effect on TS promoter
      activity. Deletion of sequences upstream or downstream of the TS essential
      promoter region, or inactivation of each of the known elements within the
      essential promoter region, had no effect on the ability of wild-type p53 to
      inhibit TS promoter activity. Our observations indicate that the inhibition of TS
      promoter activity by p53 is not due to the presence of a specific p53 negative
      response element in the TS promoter. Rather, it appears that p53 inhibits the TS
      promoter by sequestering ("squelching") one or more general transcription
      factors.

PMID- 9260895
TI  - Differential induction of HNF-3 transcription factors during neuronal
      differentiation.
AB  - We have investigated the regulation of transcription factors HNF-3alpha and HNF
      3beta during the retinoic acid-mediated differentiation of mouse P19 cells.
      Retinoic acid treatment converts P19 stem cells into neurons and astrocytes and
      we have clearly shown that gene expression of both HNF-3alpha and HNF-3beta is
      activated during this process. HNF-3alpha transcription was detected 2 h after
      addition of retinoic acid and took place in the absence of de novo protein
      synthesis. This suggests that HNF-3alpha is a primary target for retinoic acid
      action. HNF-3alpha induction displays a biphasic profile and HNF-3alpha mRNA
      reaches maximal levels at 2 and 6 days postdifferentiation. Additional
      experiments strongly suggest that the second peak is due to HNF-3alpha induction
      in postmitotic neurons. P19 stem cells, on the other hand, do not contain any
      detectable HNF-3alpha mRNA. According to our studies, the retinoic acid-mediated
      induction of HNF-3alpha occurs at the level of transcriptional initiation and is
      conferred by distal promoter sequences. In comparison to HNF-3alpha, HNF-3beta
      induction is a subsequent event and detectable levels of HNF-3beta mRNA
      materialize approximately 1 day after addition of retinoic acid to P19 stem
      cells. Time course studies firmly demonstrate that HNF-3beta mRNA peaks at about
      2 days postdifferentiation and then declines to virtually unreadable levels. This
      temporal pattern is consistent with HNF-3beta being a secondary target for
      retinoic acid. In analogy to HNF-3alpha, HNF-3beta activation also takes place at
      the level of transcriptional initiation. Recent studies implicate HNF-3alpha and
      HNF-3beta in early mammalian neurogenesis. The detection of HNF-3alpha/beta
      activation during P19 cell differentiation provides us with a convenient cell
      culture system to elucidate the induction mechanism and the precise role of both
      transcriptional regulators in the formation of neuronal cells.

PMID- 9260896
TI  - Selective inhibition of platelet-derived growth factor (PDGF) receptor
      autophosphorylation and PDGF-mediated cellular events by a quinoline derivative.
AB  - This report describes the biological effects of our original compound, Ki6783
      ((3,4-dimethoxy)-4-phenoxy-6,7-dimethoxyquinoline), a potent and selective
      inhibitor of platelet-derived growth factor (PDGF) receptor autophosphorylation.
      This compound strongly inhibited autophosphorylation of the PDGF beta-receptor in
      cultured rat glomerular mesangial cells (MC) bearing this receptor (IC50 0.1
      microM), although it did not inhibit autophosphorylation of other growth factor
      receptors even at 100 microM. In a cell-free kinase experiment, it showed
      selective inhibition of PDGF beta-receptor tyrosine kinase. A kinetic study of
      the compound to this tyrosine kinase revealed a competitive mode of action to
      ATP. [3H]Thymidine incorporation and cell proliferation of MC were inhibited by
      Ki6783 in a dose-dependent manner after Ki6783 and PDGF-BB were added to the
      culture medium. Furthermore, this compound normalized the fibrotic cell shape of
      v-sis-transformed NIH3T3 cells, which grow in an autocrine manner via the PDGF
      receptor. These effects could be explained by the inhibition of intracellular
      signal transduction triggered by PDGF receptor autophosphorylation, in which
      activation of mitogen-activated protein kinase occurs. These results suggest that
      Ki6783 is one of the more potent and selective inhibitors of PDGF receptor
      autophosphorylation and that it may be useful in ameliorating cell abnormalities
      due to excess action of PDGF and its receptor systems in several diseases.

PMID- 9260897
TI  - Retinoic acid inhibition of cell cycle progression in MCF-7 human breast cancer
      cells.
AB  - Cell cycle analysis indicates that retinoic acid (RA) inhibition of MCF-7 cell
      growth occurs through induction of G1 arrest with a concomitant reduction in the
      proportion of cells in S and G2 + M phases. RA did not affect cyclins D1, A, and
      E and cyclin-dependent kinase 2 (CDK2) expression, but significantly reduced
      cyclin D3 and CDK4 expression after 24 h. RA also inhibited cyclin B1 and CDC2
      expression, possibly responsible for the reduction of the proportion of cells in
      G2 + M and S phases. RA did not induce p16 and p27 expression, but obviously
      reduced p21 level in MCF-7 cells. The retinoid markedly reduced pRB protein level
      and abrogated pRB phosphorylation after 48 h; it also reduced transcription
      factor E2F1 expression at both the mRNA and protein levels. E2F1 promoter
      activity was reduced by 60%, which is probably responsible, at least in part, for
      the reduction of E2F1 expression in RA-treated MCF-7 cells. These observations
      demonstrate a marked effect of RA on some of the key cell cycle regulatory
      proteins in MCF-7 cells. Cyclin D3 and CDK4 are likely the early targets of RA,
      followed by reduced pRB expression and phosphorylation, as well as by the
      inhibition of the E2F1 transcription factor which controls progression from G1 to
      S phase. Most of these events precede the observed reduction in MCF-7 cell
      growth, which begins at Day 3 of RA treatment.

PMID- 9260898
TI  - Expression of SV40 large T antigen stimulates reversion of a chromosomal gene
      duplication in human cells.
AB  - Transformation of human cells is characterized by altered cell morphology,
      frequent karyotypic abnormalities, reduced dependence on growth factors and
      substrate, and rare "immortalization"-clonal acquisition of unlimited
      proliferative potential. We previously reported a marked increase in DNA
      rearrangements, arising between two duplicated segments in a transfected plasmid
      substrate, for five immortal human cell lines relative to three normal fibroblast
      strains [Finn et al. (1989) Mol. Cell. Biol. 9, 4009-4017]. We have now assessed
      reversion of a 14-kilobase-pair duplication within the hypoxanthine
      phosphoribosyl transferase (HPRT) gene locus, in a fibroblast strain during its
      normal replicative lifespan and after stable transformation with SV40 large-T
      antigen. Revertants, selected under HPRT-dependent growth conditions immediately
      after purging preexisting HPRT+ cells, were confirmed as HPRT+ by hypoxanthine
      incorporation and 6-thioguanine sensitivity. Southern blot analyses indicate loss
      from most revertant clones of a restriction fragment representing the duplicated
      HPRT region, as predicted for homologous recombination between the 14-kilobase
      pair repeats. Amplification of a subregion of HPRT mRNA implicated deletion of
      duplicated exons in 93% of revertant colonies. Reversion to HPRT+ was unaltered
      during the normal in vitro lifespan of these cells, but increased in 9 clones
      stably transformed with large-T antigen (mean = 3.8-fold; each P < 10(-5)).
      Stimulation of HPRT-reversion is abrogated in a variety of T-antigen mutants, and
      depends on continued induction of T antigen by glucocorticoid in two clones
      tested 10-30 doublings before replicative senescence. Since no immortal subclones
      arose from these clones, elevated reversion must precede immortalization.
      Increased DNA rearrangements, in cells expressing T-antigen, could facilitate the
      rare concurrence of multiple mutations necessary for immortalization.

PMID- 9260900
TI  - Differential regulation of extracellular signal-regulated kinase 1 and 2 activity
      during 12-O-tetradecanoylphorbol 13-acetate-induced differentiation of HL-60
      cells.
AB  - In this study we have analyzed short- and long-term changes in extracellular
      signal-regulated kinase (ERK) 1 and 2 activity during 12-O-tetradecanoylphorbol
      13-acetate (TPA)-induced differentiation of human promyelocytic leukemia cells.
      Immunoprecipitation of HL-60 cellular extracts with an ERK antibody followed by
      in vitro myelin basic protein phosphorylation demonstrated a rapid reduction in
      total ERK activity by 70%. Mitogen-activated protein kinase substrate peptide
      phosphorylation also demonstrated that this reduction was sustained during
      differentiation. Immunoblot analysis revealed that ERK1 and ERK2 are the
      predominant ERK isoforms present in HL-60 cells and that over a 96-h period ERK1
      protein was gradually reduced by 60% while ERK2 protein showed only a small,
      insignificant reduction. Therefore, the large, rapid decrease in total ERK
      activity could not be attributed to the gradual reductions in ERK1 or ERK2
      amounts. Immunoblot analysis with two different phosphotyrosine antibodies
      revealed a rapid decrease in ERK1 phosphotyrosine and a concurrent transient
      increase in ERK2 phosphotyrosine. These contrasting changes in phosphorylated
      ERKs were paralleled by respective shifts in mobility during SDS-PAGE analysis.
      Together these results indicate that the rapid reduction in total ERK activity is
      due to rapid tyrosine and possible threonine dephosphorylation of ERK1 but not of
      ERK2. These results also indicate that ERK1 and ERK2 are regulated by distinct
      mechanisms during TPA-induced HL-60 differentiation, suggesting that their
      biological roles are nonredundant.

PMID- 9260899
TI  - Peculiar distribution of fodrin in fat-storing cells.
AB  - Fat-storing cells (FSCs) show unique morphology containing many lipid droplets in
      the cytoplasm. In this study, we found that a membrane skeletal protein, fodrin,
      shows peculiar distribution in FSCs of rat liver. By immunofluorescence
      microscopy of FSCs in culture, intense labeling for fodrin was seen as coarse
      filaments in the cytoplasm. Especially in FSCs isolated from vitamin A-treated
      rats, the labeling was often seen as many small rings in the cytoplasm. In
      contrast, labeling for fodrin in human fibroblasts or rat adipocytes in culture
      was seen diffusely in the cell cortex. Distribution of actin, tubulin, vimentin,
      and desmin in FSCs was also examined, but none of them appeared correlated with
      fodrin. By immunoelectron microscopy using nanogold labeling with silver
      enhancement, positive labeling for fodrin was seen around some lipid droplets in
      FSCs in vivo. We assume that the peculiar distribution of fodrin may be related
      to the morphological characteristics of FSCs.

PMID- 9260901
TI  - An altered intracellular distribution of the autoantigen La/SS-B when translated
      from a La mRNA isoform.
AB  - Transcription of the gene encoding for the nuclear autoantigen La resulted in La
      mRNA isoforms. A promoter switching combined with an alternative splicing pathway
      replaced exon 1 with exon 1'. Similar to mRNAs encoding for ribosomal proteins,
      exon 1' started with a pyrimidine-rich 5'-terminus. Moreover, exon 1' contained
      5'-GC-rich regions and an oligo(U)-tail of 23 uridine residues. Exon 1' encoded
      for three open reading frames upstream of the La protein reading frame. In spite
      of this unusual structure, exon 1' La mRNAs were translated not only in vitro but
      also in transiently transfected cells. The translational efficiency of exon 1' La
      mRNA was about 14% of exon 1 La mRNA using rabbit reticulolysate for in vitro
      translation. Finally, we established permanently transfected mouse cell lines
      expressing the human exon 1 or exon 1' La mRNA isoform. In all cell lines the
      respective La mRNAs were translated to La protein. The exon 1 La mRNA-expressing
      cell lines displayed a mostly nuclear staining pattern. In contrast, a major
      portion of La protein was found in the cytoplasm of cell lines expressing exon 1'
      La mRNA.

PMID- 9260902
TI  - Amyloid beta-protein(25-35) increases cellular APP and inhibits the secretion of
      APPs in human extraneuronal cells.
AB  - Amyloid beta-protein (A beta) is the core component of the senile plaques
      occurring during Alzheimer's disease and in its aggregated form is cytotoxic for
      neuronal and extraneuronal cells. In this study, the influence of the
      spontaneously aggregating fragment A beta(25-35) on the expression and metabolism
      of beta-amyloid precursor protein (APP) was investigated in human extraneuronal
      cells. Cellular extracts and conditioned supernatants were analyzed by
      immunoblotting. A beta(25-35) strongly increased the cellular content of APP in
      cultured epithelial cells from thyroid glands and kidneys as well as in the
      promyelogranulocytotic cell line HL-60. At the same time A beta reduced the
      secretion of soluble APPs to less than one-third of its control value, but did
      not alter the secretion of fibronectin, which was used as a control protein.
      Despite these changes, APP transcription was not changed following A beta(25-35)
      treatment. These results demonstrate that A beta(25-35) strongly increases the
      APP content of extraneuronal cells by inhibiting its secretory processing. This
      may result in a deviation of APP metabolism towards an internal, potentially
      amyloidogenic pathway.

PMID- 9260903
TI  - Shedding of gangliosides by human medulloblastoma cells.
AB  - Shedding of immunosuppressive gangliosides is an important characteristic of both
      experimental and human tumors. Using a medulloblastoma cell line, Daoy, with a
      very high ganglioside expression (141 +/- 13 nmol/10(8) cells) and a well
      characterized ganglioside complement, we have now studied ganglioside shedding by
      human brain tumor cells. Shedding of gangliosides, quantified by metabolic
      radiolabeling, was significant (169 pmol/10(8) cells/h) and was generalized with
      respect to the major ganglioside carbohydrate structures (G(M2), G(M3), and
      G(D1a)). For each ganglioside, however, shedding was selective for ceramide
      structures containing shorter fatty acyl chains. Rapid and ceramide-selective
      shedding was confirmed in two additional human medulloblastoma cell lines, D341
      Med and D283 Med (112 and 59 pmol/10(8) cells/h). Significant ganglioside
      shedding is therefore a common characteristic of human medulloblastoma cells and
      may influence the biological behavior of this tumor, in view of immunosuppressive
      and other biological properties of shed gangliosides.

PMID- 9260904
TI  - Catfish thrombocytes express an integrin-like CD41/CD61 complex.
AB  - A thrombocyte-specific antigen was identified in two closely related catfish,
      Ictalurus punctatus and Ictalurus furcatus, by monoclonal antibodies 4-20 and 7
      2. The antibodies immunoprecipitate two noncovalently associated glycoprotein
      chains of Mr 180,000 and Mr 95,000. Under reducing conditions the Mr 180,000
      chain is resolved into Mr 150,000 and 32,000 subcomponents. Analysis of N
      terminal amino acid sequences indicates homology of the Mr 95,000 chain with the
      beta3 integrin subunit and homology of the Mr 150,000 chain with the alphaIIb
      integrin subunit. These antibodies induce catfish thrombocyte aggregation and
      alteration of cell shape. The data indicate conservation of the
      megakaryocyte/platelet-restricted CD41/CD61 complex in bony fish.

PMID- 9260905
TI  - Analysis of neurotrophin/receptor interactions with a gD-flag-modified
      quantitative kinase receptor activation (gD.KIRA) enzyme-linked immunosorbent
      assay.
AB  - A rapid, sensitive, and high-capacity assay has been developed to quantify ligand
      induced receptor tyrosine kinase activation in terms of receptor phosphorylation.
      The assay, termed a "kinase receptor activation" or KIRA-ELISA, utilizes two
      separate microtiter plates, one for cell culture and ligand stimulation, and the
      other for receptor capture and phosphotyrosine ELISA. The assay was developed for
      analysis of neurotrophin-induced trkA, trkB, or trkC activation. It utilizes a
      trkA, trkB, or trkC receptor fused with a 26-amino-acid polypeptide flag derived
      from HSV glycoprotein D (gD.trkA, B, or C, respectively) on the amino-terminus,
      stably transfected into CHO cells. Stimulated receptors were solubilized with
      Triton X-100 buffer and then captured in ELISA wells coated with gD-specific mAb.
      The degree of receptor autophosphorylation was quantified by anti-phosphotyrosine
      ELISA. Reproducible standard curves were generated with an EC50 of approximately
      16 ng/ml NGF for gD.trkA KIRA, 11 ng/ml for NT4/5 and 20 ng/ml for BDNF in
      gD.trkB KIRA, and 9.4 ng/ml for NT3 in gD.trkC KIRA. When the gD.trkA KIRA assay
      was used to quantify serum NGF or NT3 following administration to rats, the assay
      agreed well with currently existing ELISA assays. When the gD.trkA KIRA assay was
      used to test several NGF variants, as well as NGF stability samples, the capacity
      of the assay to quantify ligand bioactivity compared well with the more widely
      used radioreceptor binding and PC 12 cell survival assays. The gD.trk KIRA assays
      show great potential as rapid bioassays, capable of quantitative, consistent, and
      stability indicating analyses.

PMID- 9260906
TI  - Activity and inducibility of drug-metabolizing enzymes in immortalized hepatocyte
      like cells (mhPKT) derived from a L-PK/Tag1 transgenic mouse.
AB  - This report describes the establishment and characterization of the mhPKT cell
      line derived from the liver of a transgenic mouse harboring the simian virus
      (SV40) large T and small t antigens placed under the control of the 5' regulatory
      sequence of the rat L-type pyruvate kinase (L-PK) gene. mhPKT cells had a
      prolonged life span, expressed the SV40-encoded nuclear large T antigen when
      grown in glucose-enriched medium, and induced tumors when injected subcutaneously
      into athymic (nu-nu) mice. Growth on petri dishes or filters yielded multiple
      layers of cuboid cells, with numerous spaces between adjacent cells that were
      closed by junctional complexes. These bile canaliculi-like structures exhibited
      numerous microvilli in which villin, an actin-binding brush-border protein,
      colocalized with actin. These bile canaliculi-like structures appeared to be
      functional as they accumulated fluorescein. mhPKT cells conserved the expression
      of the liver-specific transcription factors HNF1, HNF3, HNF4, and DBP together
      with substantial levels of L-PK and albumin but not alpha-fetoprotein mRNA
      transcripts. mhPKT cells mainly metabolized testosterone into androstenedione and
      6beta-hydroxytestosterone, as in vivo. 3-Methylcholanthrene and 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) markedly increased ethoxyresorufin-O
      deethylase activity and the related cytochrome P450 (CYP) 1A1/2 protein, whereas
      alpha-naphtoflavone antagonized the TCDD-elicited induction. Phenobarbital
      slightly increased the CYP2B-mediated activities of pentoxyresorufin-O
      depentylase, 2beta- and 16beta-testosterone hydroxylase. mhPKT cells also had
      substantial sulfotransferase, UDP-glucuronyltransferase, and glutathione S
      transferase activities. This model may serve as a tool for long-term in vitro
      studies of xenobiotic metabolism, potent CYP inducers, and hepatocyte damage due
      to drugs and other factors.

PMID- 9260907
TI  - Interactions of transthyretin (TTR) and retinol-binding protein (RBP) in the
      uptake of retinol by primary rat hepatocytes.
AB  - The mechanism by which cells take up retinol from retinol-binding protein (RBP)
      and the role of the RBP-transthyretin (TTR) complex remain unclear. Here we
      report on retinol uptake through the RBP-TTR complex by primary cultured rat
      hepatocytes (parenchymal cells, PC) and nonparenchymal cells (NPC) following
      incubation with [3H]retinol-RBP or the [3H]retinol-RBP-TTR complex under several
      conditions. The cellular accumulation of retinol was time and temperature
      dependent in both PC and NPC. Analysis by HPLC showed that the incorporated
      [3H]retinol in NPC was mainly converted to retinyl ester, although in PC it
      remained mainly as unesterified retinol. However, the amount of retinol taken up
      from the RBP-TTR complex was nearly twofold greater than that from RBP alone. The
      uptake of [3H]retinol from protein-bound retinol was inhibited by an excess of
      either retinol-RBP or retinol-RBP-TTR complex. Moreover, retinol uptake through
      the RBP-TTR complex was inhibited by an excess of free TTR. From these results we
      postulate that TTR may take part as a positive regulator in the delivery of RBP
      bound retinol from plasma, possibly by a membrane receptor, and that retinol
      uptake takes place preferentially from the RBP-TTR complex into both PC and NPC.
      The uptake of [3H]retinol (2 microM) by PC was saturated, whereas uptake by NPC
      was not. These results indicate that the physiological importance of TTR in
      retinol delivery may be especially important to vitamin A-storing stellate (Ito)
      cells in the NPC fraction.

PMID- 9260908
TI  - Does actin polymerization status modulate Ca2+ storage in human neutrophils?
      Release and coalescence of Ca2+ stores by cytochalasins.
AB  - The aim of this paper was to establish whether actin polymerization modulated
      cytosolic Ca2+ storage in human neutrophils. Over the concentration ranges which
      inhibit actin polymerization, cytochalasins A, B, and D liberated Ca2+ from
      membrane-bound stores within neutrophils. Two Ca2+ storage sites were identified
      in neutrophils by the accumulation of the Ca2+ binding probe, chlortetracycline:
      one at the center of the cell and the other at the cell periphery. Confocal
      imaging demonstrated that cytochalasins released Ca2+ from the neutrophil
      periphery, but not from the central Ca2+ store. Ca2+ store release was coupled to
      Ca2+ influx, suggesting that the peripheral site may be a physiological store
      containing a Ca2+ influx factor. 3,3'-Dihexyloxacarbocyanine iodide staining
      organelles, which correlate with Ca2+ release sites, coalesced in neutrophils
      after treatment with cytochalasins. We propose that peripheral Ca2+ storage sites
      are restricted from coalescence by cortical polymerized actin and that Ca2+ store
      coalescence and Ca2+ release are coupled events.

PMID- 9260910
TI  - Relationship of cytoskeletal filaments to annular gap junction expression in
      human adrenal cortical tumor cells in culture.
AB  - In addition to the well-characterized surface gap junctions expressed at contact
      sites between cells, annular gap junction profiles have been localized within the
      cytoplasm of some cell populations. To study and characterize these annular
      profiles, gap junction protein type was demonstrated with Western blot and
      immunocytochemistry. The distribution of annular gap junctions and the
      relationships to cytoskeletal elements were demonstrated with immunocytochemical,
      transmission electron microscopic, or image analysis with confocal microscopy
      techniques. SW-13 adrenal cortical tumor cells expressed alpha1 gap junctions at
      areas of cell to cell contact. In addition, alpha1 gap junction annular profiles
      were seen within the cytoplasm. Actin and myosin II were found closely associated
      with these annular gap junctions, while no physical association between tubulin-
      or vimentin-containing fibers and gap junction protein could be established.
      Disruption of microfilaments with cytochalasin B treatment (10 microg/ml, 1 h)
      resulted in a decrease in the average number and an increase in the average size
      of annular gap junctions compared to control populations. The results are
      consistent with a role for cytoskeletal elements containing actin and myosin II
      in annular gap junction turnover.

PMID- 9260909
TI  - 7-Hydroxystaurosporine (UCN-01) induces apoptosis in human colon carcinoma and
      leukemia cells independently of p53.
AB  - 7-hydroxystaurosporine (UCN-01) is a more selective protein kinase C inhibitor
      than staurosporine. UCN-01 exhibits antitumor activity in experimental tumor
      models and is presently in clinical trials. Our study reveals that human
      myeloblastic leukemia HL60 and K562 and colon carcinoma HT29 cells undergo
      internucleosomal DNA fragmentation and morphological changes characteristic of
      apoptosis after UCN-01 treatment. These three cell lines lack functional p53, and
      K562 and HT29 cells are usually resistant to apoptosis. DNA fragmentation in HT29
      and K562 cells occurred after 1 day of treatment while it took less than 4 h in
      HL60 cells. Cycloheximide prevented UCN-01-induced DNA fragmentation in HT-29
      cells, but not in HL60 and K562 cells, suggesting that macromolecular synthesis
      is selectively required for apoptotic DNA fragmentation in HT29 cells. UCN-01
      induced DNA fragmentation was preceded by activation of cyclin B1/cdc2 kinase.
      Further studies in HL60 cells showed that UCN-01-induced apoptosis was associated
      with degradation of CPP32, PARP, and lamin B and that the inhibitor of caspases
      (ICE/CED-3 cysteine proteases), Z-VAD-FMK, and the serine protease inhibitor,
      DCI, protected HL60 cells from UCN-01-induced DNA fragmentation. However, only
      DCI and TPCK, but not Z-VAD-FMK, inhibited DNA fragmentation in the HL60 cell
      free system, suggesting that serine protease(s) may play a role in the execution
      phase of apoptosis in HL60 cells treated with UCN-01. Z-VAD-FMK and DCI also
      inhibited apoptosis in HT29 cells. These data demonstrate that the protein kinase
      C inhibitor and antitumor agent, UCN-01 is a potent apoptosis inducer in cell
      lines that are usually resistant to apoptosis and lack p53 and that caspases and
      probably serine proteases are activated during UCN-01-induced apoptosis.

PMID- 9260911
TI  - Expression of perlecan, a proteoglycan that binds myogenic inhibitory basic
      fibroblast growth factor, is down regulated during skeletal muscle
      differentiation.
AB  - Heparan sulfate proteoglycans (HSPG) have been shown to be involved in the
      activation of tyrosine kinase receptors by basic fibroblasts growth factor
      (bFGF), a strong inhibitor of skeletal muscle differentiation. Skeletal muscle
      fibers contact extracellular matrix (ECM) that surrounds individual fibers
      (endomysium) and bundles of several fibers (perimysium). Perlecan is a HSPG
      present in the majority of basement membranes. In this study we evaluated the
      expression and localization of perlecan during differentiation of C2C12 skeletal
      muscle cells. C2C12 myoblasts incubated with [35S]Na2SO4 synthesize a HSPG that
      can be specifically immunoprecipitated with antibodies against murine perlecan.
      The immunoprecipitated HSPG eluted from a Sepharose CL-4B with a Kav of 0.44.
      Analysis of the core protein of the HSPG immunoprecipitated from [35S]methionine
      labeled C2C12 after treatment with heparitinase revealed two polypeptides of 170
      and over 300 kDa. The amount of polypeptides immunoprecipitated decreased with
      muscle differentiation. Immunocytolocalization studies indicate that perlecan is
      localized on the myoblast surface and by immunogold staining we have demonstrated
      that it is associated with patches of incipient extracellular matrix. The
      expression of perlecan mRNA decreased substantially during skeletal muscle
      differentiation, in contrast to the increase in transcripts for specific skeletal
      muscle proteins such as myogenin and creatine kinase. By immunofluorescence
      microscopy almost no perlecan staining associated with the surface of myotubes
      was observed. All these results suggests that perlecan, a HSPG that binds
      myogenic inhibitory bFGF, normally associated with basement membranes in adult
      tissues is present on the surface of myoblasts and its expression is down
      regulated during skeletal muscle differentiation.

PMID- 9260912
TI  - Sensitivity of fibroblasts and their cytoskeletons to substratum topographies:
      topographic guidance and topographic compensation by micromachined grooves of
      different dimensions.
AB  - Fibroblasts alter their shape, orientation, and direction of movement to align
      with the direction of micromachined grooves, exhibiting a phenomenon termed
      topographic guidance. In this study we examined the ability of the microtubule
      and actin microfilament bundle systems, either in combination with or
      independently from each other, to affect alignment of human gingival fibroblasts
      on sets of micromachined grooves of different dimensions. To assess specifically
      the role of microtubules and actin microfilament bundles, we examined cell
      alignment, over time, in the presence or absence of specific inhibitors of
      microtubules (colcemid) and actin microfilament bundles (cytochalasin B). Using
      time-lapse videomicroscopy, computer-assisted morphometry and confocal microscopy
      of the cytoskeleton we found that the dimensions of the grooves influenced the
      kinetics of cell alignment irrespective of whether cytoskeletons were intact or
      disturbed. Either an intact microtubule or an intact actin microfilament-bundle
      system could produce cell alignment with an appropriate substratum. Cells with
      intact microtubules aligned to smaller topographic features than cells deficient
      in microtubules. Moreover, cells deficient in microtubules required significantly
      more time to become aligned. An unexpected finding was that very narrow 0.5
      microm-wide and 0.5-microm-deep grooves aligned cells deficient in actin
      microfilament bundles (cytochalasin B-treated) better than untreated control
      cells but failed to align cells deficient in microtubules yet containing
      microfilament bundles (colcemid treated). Thus, the microtubule system appeared
      to be the principal but not sole cytoskeletal substratum-response mechanism
      affecting topographic guidance of human gingival fibroblasts. This study also
      demonstrated that micromachined substrata can be useful in dissecting the role of
      microtubules and actin microfilament bundles in cell behaviors such as contact
      guidance and cell migration without the use of drugs such as cytochalasin and
      colcemid.

PMID- 9260913
TI  - The phosphatase inhibitor okadaic acid stimulates the TSH-induced G1-S phase
      transition in thyroid cells.
AB  - Protein phosphorylation plays an essential role in regulating many cellular
      processes in eukaryotes. Signal transduction mechanisms that are reversibly
      controlled by protein phosphorylation require also protein phosphatases (PPs).
      Okadaic acid (OA), which is a potent inhibitor of protein phosphatase 2A (PP2A)
      and protein phosphatase 1, elicits phosphorylation of many proteins in
      unstimulated cells and induces different cellular responses, including
      transcriptional activation, shape changes, and pseudomitotic state. In this
      study, the effects of OA on rat thyroid cells (FRTL-5 strain) were analyzed to
      evaluate the role of serine/threonine phosphatases in hormone-induced thyroid
      cell proliferation. OA at a concentration range between 0.1 and 1 nM stimulated
      thyroid cell growth. Furthermore, 0.25 nM OA increased about 3.5-fold the
      thyrotropin (TSH)-induced DNA synthesis in quiescent cells. OA treatment also
      stimulated cell proliferation induced by drugs that mimic TSH effect, such as 8Br
      cAMP and cholera toxin, suggesting that PP2A activity was relevant in the cAMP
      pathway activated by the hormone. Flow cytometry experiments showed that OA
      significantly increased the fraction of TSH-stimulated quiescent cells entering
      the S phase. In order to define the mechanisms underlying the observed
      stimulatory effect of OA on thyroid cell growth, expression of genes relevant in
      the G1-S phase transition was evaluated. A 2-fold increase in the level of cyclin
      D1 mRNA expression was found by Northern blot analysis in OA-treated cells.
      Although cdk2 gene expression was not modulated by the same OA treatment, an
      increase in Cdk2 protein was revealed by immunoprecipitation experiments.
      Moreover, OA modifies the phosphorylation pattern of the tumor suppressor
      retinoblastoma protein, a key event in the G1-S phase transition. Therefore,
      these experiments reveal that PP2A phosphatases play an important role in thyroid
      cell growth and can act at multiple sites in the TSH pathways driving cells to S
      phase.

PMID- 9260914
TI  - Involvement of phosphatidylinositide 3'-kinase and Rac in platelet-derived growth
      factor-induced actin reorganization and chemotaxis.
AB  - Previous work has suggested a role for phosphatidylinositide 3'-kinase (PI3
      kinase) in platelet-derived growth factor (PDGF)-induced actin reorganization and
      chemotaxis. In support of this notion, we show in this report that the PI3-kinase
      inhibitor wortmannin inhibits chemotaxis of PDGF beta-receptor expressing porcine
      aortic endothelial (PAE/PDGFR-beta) cells. Treatment with wortmannin resulted in
      a dose-dependent decrease in chemotaxis with an IC50 value of about 15-20 nM.
      Higher concentrations of wortmannin also reduced basal random migration of
      transfected cells in the absence of PDGF. We also investigated the role of Rac in
      PDGF-induced actin reorganization and cell motility. Overexpression of wt Rac in
      PAE/PDGFR-beta cells led to an increased cell motility and edge ruffling in
      response to PDGF-BB, compared to control cells. In PAE/PDGFR-beta cells
      transfected with inducible V12Rac (a constitutively active Rac mutant), membrane
      ruffling occurred in the absence of PDGF stimulation and was independent of PI3
      kinase activity. On the other hand, PAE/PDGFR-beta cells transfected with
      inducible N17Rac (a dominant negative Rac mutant) failed to show membrane
      ruffling in response to PDGF stimulation. Together with previous observations,
      these data indicate that activation of PI3-kinase is crucial for initiation of
      PDGF-induced cell motility responses and that Rac has a major role downstream of
      PI3-kinase, in this pathway.

PMID- 9260915
TI  - Regulation of lipid signaling pathways for cell survival and apoptosis by bcl-2
      in prostate carcinoma cells.
AB  - Compelling evidence indicates that activation of the JNK/SAPK signaling pathway
      is obligatory for apoptosis induction by multiple cell stresses that activate the
      sphingomyelin cycle. Moreover, ectopic expression of bcl-2 can impair apoptosis
      signaling by most of the cell stresses that activate the ceramide/JNK pathway.
      Here we show that enforced expression of bcl-2 protects prostate carcinoma cells
      against the induction of apoptosis by exogenous C2-ceramide. Moreover, enforced
      bcl-2 expression blocked the capacity of C2-ceramide to activate JNK1, indicating
      bcl-2 functions at the level of JNK1 or upstream of JNK1 in the ceramide/JNK
      pathway. The contribution of bcl2 to the regulation of the arachidonate pathway
      for prostate carcinoma cell survival was also investigated using highly selective
      inhibitors of arachidonate metabolism. Our results indicate bcl-2 can protect
      cells against diminished availability of arachidonic acid, 12-HETE, and 15-HETE.
      Finally, arachidonic acid substantially suppresses the induction of apoptosis by
      C2-ceramide, providing evidence for the opposing influences of these lipid
      signaling pathways in the mediation of prostate carcinoma cell survival. These
      results provide evidence for opposing influences of the ceramide and arachidonate
      signaling pathways in the mediation of cell death and cell survival,
      respectively, in prostate carcinoma cells and suggest a dual role for bcl-2 in
      this context.

PMID- 9260916
TI  - Endoplasmic reticulum to Golgi trafficking in multinucleated skeletal muscle
      fibers.
AB  - The organization of membrane trafficking between endoplasmic reticulum and Golgi
      within multinucleated muscle fibers was analyzed. We found that markers for the
      compartment involved in endoplasmic reticulum to Golgi trafficking exhibited
      perinuclear as well as interfibrillar localization. Furthermore, these markers
      showed prominent colocalization with microtubules. To analyze membrane
      trafficking, we followed the temperature-controlled transport of the G protein of
      the mutant vesicular stomatitis virus, tsO45, in isolated myofibers. Perinuclear
      and cross-striated staining were seen at 39 degrees C, while at 15 degrees C a
      diffuse staining component appeared along a subset of interfibrillar
      microtubules. At 20 degrees C, bright Golgi spots were seen to be associated with
      microtubules that appeared as circumnuclear rings and longitudinal bundles.
      Beneath the motor end plate, however, the organization of the Golgi elements and
      microtubules was found to be distinctive. Retrograde trafficking induced by
      brefeldin A resulted in the disappearance of the Golgi spots throughout the
      myofibers and the appearance of staining along microtubules. Thus, interfibrillar
      membranes seem to be active in protein export, and trafficking between
      endoplasmic reticulum and Golgi elements occurred throughout the myofibers. The
      results suggest that microtubules served as tracks for the two-way trafficking
      between the endoplasmic reticulum and the Golgi compartment.

PMID- 9260917
TI  - Differential effects of EGF and amphiregulin on adhesion molecule expression and
      migration of colon carcinoma cells.
AB  - Epidermal growth factor (EGF) is a potent morphogen affecting cell shape and
      motility through regulation of adhesive interactions. We have characterized the
      morphological effects of EGF on GP2d and GP5d colon carcinoma cell lines and have
      compared the ability of the heparin-binding EGF receptor ligand amphiregulin (AR)
      to elicit the same effects. EGF induced a marked epithelial-mesenchymal
      transition in both cell lines. This effect was evident at 7 pM EGF and was
      associated with a reduction in cellular adherens junctions and diminished cell
      cell contact; it was also associated with an increase in expression of alpha2
      integrin as well as enhanced adhesion to the substratum and cell spreading. These
      changes in adhesion molecule expression were accompanied by enhanced migration on
      collagen. Blockade of cell growth with mitomycin C did not prevent the EGF
      induced morphological change, showing that the mitogenic and morphogenic
      responses of the GP cells were separable. The phosphatidyl inositol (PI) 3-kinase
      inhibitor wortmannin inhibited basal proliferation but had no effect on the EGF
      induced morphological change, further suggesting that the PI 3-kinase pathway was
      not involved in the morphogenic response of these cells. Amphiregulin stimulated
      proliferation of both cell lines, but could only elicit a modest morphological
      change if used at considerably higher doses or if growth was blocked with
      mitomycin C. In cells treated with 55 nM AR, alpha2-integrin expression was
      slightly increased; however, unlike the EGF case, adherens junctions remained
      intact. These differences in the ability of EGF and amphiregulin to affect
      cellular adhesion and migration may be significant factors influencing normal and
      tumor cell behavior.

PMID- 9260918
TI  - v-src-induced cell shape changes in rat fibroblasts require new gene
      transcription and precede loss of focal adhesions.
AB  - The mechanism of v-src-induced morphological transformation is still obscure. We
      compared LA29 rat fibroblasts, which express a temperature-sensitive (ts) v-src
      mutant, with D1025 rat fibroblasts, transfected with a ts mutant of v-fps. Upon
      transformation, LA29 cells adopted an elongated shape with reduced focal
      adhesions and loss of actin stress fibers. In contrast, activation of v-fps in
      D1025 cells had little effect on morphology. In both cells, paxillin was strongly
      tyrosine phosphorylated upon activation of the kinases. This indicates that
      paxillin phosphorylation is not required, or not sufficient, for the v-src
      induced disruption of focal adhesions. As previously described by others, v-src
      activated the ras-MAP kinase (MAPK) pathway, as indicated by tyrosine
      phosphorylation of the rasGAP-associated proteins p62 and p190 and MAPK
      phosphorylation. Since MAPK affects transcription, this suggested that novel gene
      transcription was required. This notion was confirmed using actinomycin D and
      cycloheximide, which did not impair activation of v-src kinase activity, but
      completely blocked v-src-induced morphological changes, as demonstrated using
      image analysis. Furthermore, we observed that v-src-induced changes in cell shape
      occurred before the reduction in number and size of focal adhesions. We conclude
      that v-src-induced transformation of rat fibroblasts depends on synthesis of a
      protein, which induces rapid changes in cell shape that precede the loss of focal
      adhesions.

PMID- 9260919
TI  - Activation of calcium signaling in isolated rat hepatocytes is accompanied by
      shape changes of microvilli.
AB  - Preceding studies using the hamster insulinoma cell line, HIT, and isolated rat
      hepatocytes have shown that two essential components of the Ca2+ signaling
      pathway, the ATP-dependent Ca2+ store and the store-coupled Ca2+ influx pathway,
      are both located in microvilli covering the surface of these cells. Microvilli
      derived vesicles from both cell types exhibited anion and cation pathways which
      could be inhibited by anion and cation channel-specific inhibitors. These
      findings suggested that the microvillar tip compartment forms a space which is
      freely accessible for external Ca2+, ATP, and IP3. The entry of Ca2+ into the
      cytoplasm, however, is largely restricted by the microvillar core structure, the
      dense bundle of actin microfilaments acting as a diffusion barrier between the
      microvillar tip compartment and the cell body. Moreover, evidence has been
      presented that F-actin may function as ATP-dependent and IP3-sensitive Ca2+ store
      that can be emptied by profilin-induced depolymerization or reorganization [K.
      Lange and U. Brandt (1996) FEBS Lett. 395, 137-142]. Here we demonstrate the
      tight connection between microvillar shape changes and the activation of the Ca2+
      signaling system in isolated rat hepatocytes. Using a combination of scanning
      electron microscopy (SEM) and fura-2 fluorescence technique, we confirmed a
      consequence of the "diffusion barrier" concept of Ca2+ signaling: Irrespective of
      the type of the applied stimulus, activation of the Ca2+ influx pathway is
      accompanied by changes in the structural organization of microvilli indicative of
      the loss of their diffusion barrier function. We further show that the cell
      surfaces of unstimulated hepatocytes isolated by either the collagenase or the
      EDTA perfusion technique are densely covered with microvilli predominantly of a
      short and slender type. Beside this rather uniformly shaped type of microvilli, a
      number of dilated surface protrusions were observed. Under these conditions the
      cells displayed the well known rather high basal [Ca2+]i of 200-250 nM as
      repeatedly demonstrated for freshly isolated hepatocytes. However, addition of
      the serine protease inhibitor, phenylmethanesulfonyl fluoride (PMSF), to the cell
      suspension immediately after its preparation reduced the basal cytoplasmic Ca2+
      level to about 100 nM. Concomitantly, dilated surface protrusions disappeared,
      and cell surfaces exclusively displayed short, slender microvilli. Activation of
      the Ca2+ signaling pathway by vasopressin, as well as by the IP3-independent
      acting Ca2+ store inhibitor, thapsigargin, was accompanied by a conspicuous
      shortening and dilation of microvilli following the same time courses as the
      respective increases of [Ca2+]i induced by the effectors. Furthermore, the
      abundance of the large form of surface protrusions on isolated hepatocytes
      positively correlated with the size of a cellular Ca2+/Fura-2 compartment which
      is rapidly depleted from Ca2+ by extracellular EGTA. These findings support the
      postulated localization of the store-coupled Ca2+ influx pathway in microvilli of
      HIT cells also for hepatocytes and are in accord with the notion of a
      cytoskeletal diffusion barrier regulating the flux of external Ca2+ via the
      microvillar tip region in the cytoplasm.

PMID- 9260920
TI  - Immunoseparation and immunodetection of nucleic acids labeled with halogenated
      nucleotides.
AB  - A novel methodology for labeling, isolation, and detection of nucleic acids is
      described. Nucleic acid isolation is based on in vivo or in vitro incorporation
      of BrU or BrdU to either RNA or DNA, respectively, followed by
      immunoprecipitation of the labeled nucleic acid utilizing anti-BrdU MoAb, which
      crossreacts with BrU, attached to solid particles. Filter-bound bromine-labeled
      DNA or RNA was detected by immunoblotting with anti-BrdU MoAb, by a combined
      Southern/Western or Northern/Western approach, respectively. This method was
      applied to isolate and detect rRNA and mRNA from human cells, plasmid DNA from
      bacterial cells, and in vitro synthesized DNA. Newly transcribed BrU-labeled mRNA
      was recovered from the immunoprecipitates and analyzed by RT-PCR to study phorbol
      ester-mediated regulation of interleukin 1 gene transcription in human leukemic
      HL-60 or lymphoma U937 cells. The plasmid DNAs were isolated by
      immunoprecipitation from transformed bacterial cultures that were grown in the
      presence of BrdU and were detected immunochemically on filters. Likewise, the
      products of RT-PCR and Klenow polymerase-catalyzed DNA synthesis in which dTTP
      was replaced with BrdUTP were detected by immunoblotting. Since the method allows
      one to selectively separate or detect nucleic acids only synthesized during a
      pulse of the precursor, it can uniquely be used to identify nascent gene
      transcripts or the transcripts synthesized within specific time windows, e.g.,
      after induction of differentiation, carcinogenesis, or drug treatment, and
      distinguish such transcripts from preexisting ones. In addition, this approach
      offers a simple and inexpensive alternative for preparing labeled DNA as well as
      RNA probes for use in a variety of hybridization protocols. Due to the low
      toxicity of BrU and BrdU, this approach can be used in analysis of gene
      transcription or DNA replication in vivo.

PMID- 9260921
TI  - Amyloid beta-protein induces necrotic cell death mediated by ICE cascade in PC12
      cells.
AB  - A major component of Alzheimer's disease plaque amyloid beta protein (betaAP)
      showed the cytolytic activity to rat pheochromocytoma PC 12 cells. Nuclear
      morphological study revealed that betaAP-induced cytolytic activity is due to
      necrotic cell death, rather than apoptotic cell death. To examine the molecular
      machinery of betaAP-induced necrotic cell death in detail, I investigated the
      direct involvement of caspase. When nerve growth factor-treated and -untreated
      PC12 cells were incubated with the synthesized tetrapeptide inhibitors of
      caspase, YVAD-CHO (Ac-Tyr-Val-Ala-Asp-CHO) or DEVD-CHO (Ac-Asp-Glu-Val-Asp-CHO),
      betaAP-induced necrotic cell death was prevented. In addition, the interleukin
      1beta converting enzyme (ICE) subfamily activation preceded CPP32 subfamily
      activation during betaAP-induced necrotic cell death. On the basis of these
      findings, I suggest that betaAP induces necrotic cell death mediated by the ICE
      cascade and that the ICE cascade may possibly be involved in Alzheimer's disease.

PMID- 9260922
TI  - Still immunodetectable nuclear RNPs are extruded from the cytoplasm of
      spontaneously apoptotic thymocytes.
AB  - The fate of different nuclear ribonucleoprotein (RNP) components was investigated
      during spontaneous apoptosis of thymocytes using specific monoclonal antibodies
      against snRNPs, hnRNPs, and ribosomal proteins at light and electron microscopy
      levels and by flow cytometry. It was found that, during apoptosis, nuclear RNP
      containing structures (perichromatin granules, interchromatin granules, and
      perichromatin fibrils) segregate in the interchromatin space and cluster into
      heterogeneous aggregates of granules in which some of the structures may still be
      recognized morphologically. Along with the progress of apoptosis, the clusters
      are extruded from the nucleus into the cytoplasm, from which they are finally
      released via cytoplasmic extrusions. At all these stages, RNPs inside the
      clusters are always recognized by specific antibodies, even when they bleb out of
      the cell surface, thus suggesting that degradation of RNPs might be only partial
      during apoptosis. This could be potentially harmful in genetically susceptible
      subjects, as the appropriate MHC class II molecules may capture and present
      normally cryptic self-peptides. It is tempting to speculate that this event might
      have implications in the etiology of autoimmune diseases.

PMID- 9260923
TI  - The actin binding domain of the epidermal growth factor receptor is required for
      EGF-stimulated tissue invasion.
AB  - NIH-3T3 fibroblasts expressing epidermal growth factor receptors (EGFRs) lacking
      the actin binding domain (ABD) were analyzed for their EGF-induced capacity to
      invade a bone marrow stromal cell (BMSC) monolayer. The fibroblasts display a
      reduction in the percentage of cytoskeleton-associated EGFRs. Furthermore, EGF
      induced tyrosine kinase activity is unaffected by the mutation. Cells expressing
      the mutant EGFRs hardly invade a BMSC monolayer upon EGF stimulation in contrast
      to cells expressing wild-type EGFRs. Using the same cells no difference was
      observed in PDGF-induced invasion, which ligand was as potent in both cell types
      as EGF was in wild-type cells. Inhibition of both the phosphatidyl inositol-3
      kinase (PI-3-K) and lipoxygenase pathways in wild-type cells mimicked the effect
      of the ABD deletion. Our results point to an important role for the ABD of the
      EGFR in EGF-induced tissue invasion.

PMID- 9260924
TI  - Transcriptional regulation of the murine multidrug resistance gene mdr1b by
      progesterone occurs via an indirect mechanism.
AB  - The murine multidrug resistance gene mdr1b is highly induced in the endometrium
      during pregnancy. Evidence suggests that induction occurs mainly as a result of
      progesterone action. To study the molecular mechanisms involved in this
      induction, 5'-flanking sequences between -540 and +97 of the mdr1b gene were
      fused to the reporter gene, bacterial chloramphenicol acetyltransferase
      (p540CAT). Unlike most progesterone-responsive genes, mdr1b is preferentially
      activated by the A form of the progesterone receptor. We now report that
      activation is not observed with a DNA-binding domain mutant of progesterone
      receptor A (PRA) suggesting that induction occurs at the transcriptional level.
      Time course experiments demonstrated that induction was first observed 12 hr
      after hormone addition, suggestive of a secondary (or late) response gene.
      Sequence comparison highlighted the region M1 (-234 to -206), which contains a
      partially conserved progesterone response element. Its functional significance
      was evaluated by expression assays and gel shift analysis. Reporter plasmids with
      modifications of this element were transfected into HeLa cells. Constructs
      containing the native M1 element, or a mutated element (M1mt) that eliminated any
      similarity to a progesterone response element, were induced four-fold by
      progesterone whereas an element containing a consensus progesterone response
      element (M1PRE) was induced eight-fold. In addition, by gel shift analysis, the
      M1 element did not bind the progesterone receptor or any other factors. This
      suggested that the M1 region does not participate in the response to
      progesterone. 5' Nested deletion analysis, used to identify other regions of the
      upstream regulatory region that contributed to induction by progesterone,
      demonstrated that enhancer sequences between -122 and -65, which contain binding
      sites for C/EBPbeta and NF-Y, were important. Mutations in the binding sites for
      these factors decreased induction by progesterone. On the basis of our studies
      using 540 bp of upstream sequence, mdr1b is activated transcriptionally by
      progesterone, in an indirect manner dependent on basal factors.

PMID- 9260925
TI  - Anti-(U1)snRNP autoantibodies inhibit homologous pairing activity of the human
      recombination complex.
AB  - The co-purification of the U1snRNP particle with a high-molecular-weight human
      homologous pairing activity has been observed consistently. Using human
      autoimmune sera directed against various snRNPs, it has been found that
      autoantibody binding to antigenic determinants specifically associated with the
      U1snRNP particle inhibits the formation of paired DNA molecules by the human
      homologous pairing activity. Immunoprecipitation of U1snRNP with anti-(U1)RNP
      autoantibodies significantly reduced the homologous pairing activity in these
      fractions. NaDodSO4-PAGE analysis of immunoprecipitated samples has revealed
      their content to be mostly composed of anti-(U1)RNP precipitable material. Taken
      together, these results suggest that some biochemical reactions in the process of
      homologous pairing promoted by high-molecular-weight complex are dependent upon
      U1snRNP components. It is postulated that the U1snRNP may be associated with the
      recombination complex in human cells.

PMID- 9260926
TI  - Identification of a promoter for the latent membrane protein 1 gene of Epstein
      Barr virus that is specifically activated in human epithelial cells.
AB  - Latent membrane protein 1 (LMP 1) is one of two Epstein-Barr virus (EBV)-encoded
      proteins that expressed in nasopharyngeal carcinoma (NPC) cells. Previous studies
      showed that a 3.5-kb transcript of the LMP 1 gene, in addition to the 2.8-kb
      transcript, was detected in a B95-8-EBV-containing, nude mice-passaged NPC tumor,
      C15. This indicated that a transcript was initiated from a region 5' to the
      putative promoter, ED-L1. We have isolated an EBV variant from a NPC tissue, and
      this virus strain contained a more pathogenic LMP 1 gene. DNA sequence analysis
      of the 5'-upstream region showed distinct variations as compared to that of B95-8
      strain. To test if the LMP 1 gene of the NPC strain also contained an upstream
      promoter, we generated a series of deletion plasmids encompassing positions 
      1,030 to +20 of the LMP 1 promoter and tested for their abilities to drive the
      expression of the reporter gene in human epithelial cell lines, C-33A and NPC
      TW076. We found that the region between -643 and -496 contained a promoter
      activity that was approximately five-fold higher than the putative promoter, ED
      L1. This region between -643 and -496 was designated as ED-L1E. C-33A cells
      containing the genomic clone pT7(E) or the clone that had deleted a 94-bp ED-L1
      sequence (delta94) was used to determine the transcription initiation sites by
      RNase protection assay. Results showed that a transcription initiation site was
      located at nucleotide 170,099 ("A") of EBV genome. The transcript was expressed
      in NPC biopsies and in human primary normal epithelial cells transfected with
      pT7(E) and delta94, respectively, as examined by reverse transcriptase-polymerase
      chain reaction (RT-PCR) analysis. Furthermore, the ED-L1E was not regulated by
      the EBV-encoded nuclear antigen 1-mediated transcriptional enhancer family of
      repeats (FR) in C-33A cells. Our results suggested that the ED-L1E was
      specifically activated in epithelial cells. The biological significance of the
      selective usage of the ED-L1E promoter was discussed.

PMID- 9260927
TI  - Characterization of the INT6 mammary tumor gene product.
AB  - INT6 is a unique gene, highly conserved throughout evolution and associated with
      mammary tumorigenesis in the mouse. Although it is expressed in all adult tissues
      of the mouse and early in embryonic development, its function is unknown. To
      study the normal distribution and the potential function of the Int6 gene
      products, we produced antibodies against synthetic peptides specific for the Int6
      protein. Western blot and immunoprecipitation analysis demonstrated a 43-kD major
      gene product that is localized in the cytosolic fraction of mammary cell
      homogenates. This latter observation is supported by immunoperoxidase analysis,
      which shows a strong staining anti-Int6 peptide in the perinuclear region of the
      HC11 mammary epithelial cell line, suggesting a possible localization in the
      Golgi apparatus. Further immunocytochemical studies in the mouse embryo show that
      Int6 expression is prevalent in migrating neural crest cells, in the notochord,
      and in condensing cartilage between 9.5 and 14.5 days of development. In these
      embryonic tissues, Int6 staining co-localizes with the staining of ricinus
      lectin, and giantin, proteins that are specifically associated with the Golgi
      apparatus. The restricted expression of the protein within the Golgi apparatus
      and its strong conservation throughout evolution suggest that Int6 may perform an
      essential cellular function.

PMID- 9260928
TI  - Dynamics of cell cycle regulators: artifact-free analysis by recultivation of
      cells synchronized by centrifugal elutriation.
AB  - Studies on the molecular properties of cell cycle regulators in animal cells
      require cell preparations highly enriched in particular cell cycle phases.
      Centrifugal elutriation is frequently used to synchronize cells because this
      technique was thought to cause only minimal distortions in protein expression or
      metabolic functions. However, in primary chicken erythroblasts, we consistently
      observed artefacts in mitotic cyclin mRNA expression and p70 S6 kinase activity,
      which were clearly caused by the elutriation procedure. Therefore, we modified
      the standard protocol by reseeding various elutriated fractions into
      preconditioned medium, a process termed recultivation, and harvesting after an
      appropriate amount of time. This avoided the pleiotropic effects caused by stress
      and lack of growth factor supply during elutriation. Using this recultivation
      procedure, highly synchronous progression starting from any given cell cycle
      phase could be achieved for a variety of cell types, including primary, factor
      dependent cells of hematopoietic origin. Mitotic cyclin expression and S6 kinase
      activity was found to be normal again in recultivated cultures, as opposed to
      elutriated ones. Finally, monitoring of mitosis-specific cyclin A degradation in
      recultivated G2 phase cells showed that recultivation provided an excellent tool
      to follow cells through M phase into G1 without the requirement for a chemical
      cell cycle block.

PMID- 9260929
TI  - Lactadherin (formerly BA46), a membrane-associated glycoprotein expressed in
      human milk and breast carcinomas, promotes Arg-Gly-Asp (RGD)-dependent cell
      adhesion.
AB  - Lactadherin, a major glycoprotein of the human milk fat globule membrane, is
      abundant in human breast milk and expressed in human breast carcinomas.
      Previously, we have shown that the mature protein, formerly known as BA46, has
      three domains: an epidermal growth factor (EGF)-like domain containing an Arg-Gly
      Asp (RGD) cell adhesion sequence and C1 and C2 domains similar to those found in
      coagulation factors V and VIII. An alignment of lactadherin with its bovine
      (MGP57/53) and murine (MFG-E8) homologs shows that the RGD sequence has been
      conserved during evolution, suggesting that the RGD sequence is not fortuitous.
      We demonstrate that lactadherin purified using Triton X-114 phase partitioning
      promotes RGD-dependent cell attachment of green monkey kidney cells (MA104),
      mouse fibroblast cells (3T3-L1), and breast carcinoma cells (ELL-G). A
      lactadherin-specific monoclonal antibody, Mc3, inhibits attachment to purified
      lactadherin, suggesting that contaminants in the purification are not responsible
      for binding. In addition, the anti-integrin alpha(v)beta3 monoclonal antibody
      LM609 inhibits cell attachment of MA104 cells to lactadherin. These results
      demonstrate that lactadherin promotes RGD-dependent cell adhesion via integrins.
      Denaturation of lactadherin with heat and reducing conditions diminished cell
      attachment, suggesting that optimal cell attachment to RGD is dependent on the
      structural presentation of the sequence.

PMID- 9260930
TI  - Cloning and characterization of two human polyspecific organic cation
      transporters.
AB  - Previously we cloned a polyspecific transporter from rat (rOCT1) that is
      expressed in renal proximal tubules and hepatocytes and mediates electrogenic
      uptake of organic cations with different molecular structures. Recently a
      homologous transporter from rat kidney (rOCT2) was cloned but not characterized
      in detail. We report cloning and characterization of two homologous transporters
      from man (hOCT1 and hOCT2) displaying approximately 80% amino acid identity to
      rOCT1 and rOCT2, respectively. Northern blots showed that hOCT1 is mainly
      transcribed in liver, while hOCT2 is found in kidney. Using in situ hybridization
      and immunohistochemistry, expression of hOCT2 was mainly detected in the distal
      tubule where the transporter is localized at the luminal membrane. After
      expression in Xenopus laevis oocytes, hOCT1 and hOCT2 mediate tracer influx of N
      1-methylnicotinamide (NMN), tetraethylammonium (TEA), and 1-methyl-4
      phenylpyridinium (MPP). For cation transport by hOCT2 apparent K(m) and K(i)
      values were determined in tracer flux measurements. In addition, electrical
      measurements were performed with voltage-clamped oocytes. Similar to rOCT1,
      cation transport by hOCT2 was pH independent, electrogenic, and polyspecific;
      however, the cation specificity was different. In voltage-clamped hOCT2
      expressing oocytes, inward currents were induced by superfusion with MPP, TEA,
      choline, quinine, d-tubocurarine, pancuronium, and cyanine863. Cation transport
      in distal tubules is indicated for the first time. Here hOCT2 mediates the first
      step in cation reabsorption. hOCT1 may participate in hepatic excretion of
      organic cations.

PMID- 9260932
TI  - Expression plasmid vectors with convenient subcloning sites in lambda gt11 that
      efficiently produce detectable tagged proteins.
AB  - We have generated cDNA expression vectors that efficiently produce tagged
      proteins. The newly introduced cloning site of this plasmid facilitates
      subcloning of cDNA in the lambda gt11 phage into the plasmid vector. Because the
      cDNA is inserted next to the motifs of the tagged DNA sequence, the protein
      produced by the tag sequence-coupled cDNA is easily detected by Western blot
      analysis or immunoprecipitation using commercially available antibodies. The
      double-tagged protein significantly enhances the efficiency of Western blot and
      immunoprecipitation detection as compared with the single-tagged protein.

PMID- 9260931
TI  - Production of biologically active recombinant tilapia insulin-like growth factor
      II polypeptides in Escherichia coli cells and characterization of the genomic
      structure of the coding region.
AB  - Insulin-like growth factor-II (IGF-II) is a fetal growth factor in humans, but
      has not been clearly identified in fish up to now. For a detailed understanding
      of the physiological response of fish IGF-II, the first step was to clone tilapia
      IGF-II cDNA from the brain cDNA library, coding the region of genomic DNA, and
      also expressing tilapia IGF-II polypeptides from Escherichia coli. Tilapia cDNA
      sequences total 1,977 bp, and predicted nucleotide sequences and amino acid
      sequences of tilapia share 77.9% and 90.7% homology identity with rainbow trout
      IGF-II, respectively. The genomic structure of the tilapia prepro-IGF-II coding
      region is very difficult to sequence in mammals and birds. The cloned tilapia IGF
      II gene coding region appears much more complex than in other vertebrates. In
      tilapia IGF-II, the first coding exon I encoding part of the signal peptide
      sequence is 25 amino acids shorter than the first coding exon of mammals and
      birds. The other 23 amino acids of the signal peptide, and the first amino acids
      of the B domain and C domain are encoded by tilapia coding exon 2. The C, A, and
      D domains, and the first 20 amino acids of the E peptide are encoded by tilapia
      coding exon 3. The other E peptides and the 3' untranslated region (UTR) region
      are encoded by tilapia coding exon 4. These data show that the IGF-II genes have
      significantly differing structures in vertebrate evolution, and there are
      differences of interrupting introns in the IGF-I genomic structure compared with
      mammals. To obtain recombinant biologically active polypeptides, tilapia IGF-II B
      C-A-D domains were amplified using the polymerase chain reaction (PCR), then
      ligated with glutathione S-transferase (GST, pGEX-2T vector). Tilapia recombinant
      IGF-II protein was purified and characterized in E. coli. The fusion protein was
      also digested with thrombin and appeared as a recombinant IGF-II polypeptide
      single band with a molecular mass of 7 kD. The recombinant tilapia IGF-II protein
      biological function was measured by stimulation of [3H]thymidine incorporation.
      The assay concentration was set up from 0 to 120 nM to stimulate tilapia ovary
      cell line (TO-2) significantly to uptake thymidine. The results suggest that the
      recombinant IGF-II protein was dose dependent.

PMID- 9260933
TI  - Cloning and sequence analysis of cDNA encoding rat carboxypeptidase D.
AB  - Carboxypeptidase D (CPD) is a recently described 180-kD enzyme with
      carboxypeptidase E-like enzymatic properties. CPD has been proposed to be present
      in the secretory pathway and to contribute to peptide hormone processing in the
      Cpe(fat)/Cpe(fat) mouse, which lacks functional CPE. Sequence analysis of cDNA
      clones encoding rat CPD show the protein to contain an amino-terminal signal
      peptide, three carboxypeptidase-like domains, a putative transmembrane domain,
      and a 60-amino-acid cytoplasmic tail. Whereas active site, substrate-binding, and
      metal-binding residues of other metallocarboxypeptidases are conserved in the
      first two domains of CPD, several of the critical residues are not conserved in
      the third domain; this third domain is not predicted to form an active
      carboxypeptidase. The overall homology between rat CPD and the duck homolog gp180
      is high, with 75% amino acid identity. The three carboxypeptidase domains show
      66%, 83%, and 82% amino acid identity between rat CPD and duck gp180. Homology is
      also high in the transmembrane domain (86%) and in the cytoplasmic tail (97%).
      The mouse Cpd gene maps to the medial portion of chromosome 11, approximately
      45.5 cM distal to the centromere. Northern blot analysis of CPD mRNA shows major
      bands of approximately 8 and 4 kb in many rat tissues, and additional species
      ranging from 1.4 to 5 kb that are expressed in some tissues or cell lines. CPD
      mRNA is detectable in most tissues examined, and is most abundant in hippocampus,
      spinal cord, atrium of the heart, colon, testis, and ovaries. In situ
      hybridization of CPD mRNA shows a distribution in many cells in rat brain and
      other tissues, with high levels in hippocampus, olfactory bulb, and the
      intermediate pituitary. The broad distribution is consistent with a role for CPD
      in the processing of many peptides and proteins that transit the secretory
      pathway.

PMID- 9260934
TI  - Cell cycle characteristics of thermophilic archaea.
AB  - We have performed a cell cycle analysis of organisms from the Archaea domain.
      Exponentially growing cells of the thermophilic archaea Sulfolobus solfataricus
      and Sulfolobus acidocaldarius were analyzed by flow cytometry, and several
      unusual cell cycle characteristics were found. The cells initiated chromosome
      replication shortly after cell division such that the proportion of cells with a
      single chromosome equivalent was low in the population. The postreplication
      period was found to be long; i.e., there was a considerable time interval from
      termination of chromosome replication until cell division. A further unusual
      feature was that cells in stationary phase contained two genome equivalents,
      showing that they entered the resting stage during the postreplication period.
      Also, a reduction in cellular light scatter was observed during entry into
      stationary phase, which appeared to reflect changes not only in cell size but
      also in morphology and/or composition. Finally, the in vivo organization of the
      chromosome DNA appeared to be different from that of eubacteria, as revealed by
      variation in the relative binding efficiency of different DNA stains.

PMID- 9260935
TI  - The Helicobacter pylori gene encoding phosphatidylserine synthase: sequence,
      expression, and insertional mutagenesis.
AB  - The Helicobacter pylori pss gene, coding for phosphatidylserine synthase (PSS),
      was cloned and sequenced in this study. A polypeptide of 237 amino acids was
      deduced from the PSS sequence. H. pylori PSS exhibits significant amino acid
      sequence identity with the PSS proteins found in the archaebacterium
      Methanococcus jannaschii, the gram-positive bacterium Bacillus subtilis, and the
      yeast Saccharomyces cerevisiae but none with its Escherichia coli counterpart.
      Expression of the putative pss gene in maxicells gave rise to a product of
      approximately 26 kDa, which is in agreement with the predicted molecular mass of
      26,617 Da. A manganese-dependent PSS activity was found in the membrane fractions
      of the E. coli cells overexpressing the H. pylori pss gene product. This result
      indicates that this enzyme is a membrane-bound protein, a conclusion which is
      supported by the fact that the PSS protein contains several local hydrophobic
      segments which could form transmembrane helices. The pss gene was inactivated
      with a chloramphenicol acetyltransferase cassette on the plasmid. However, an
      isogenic pss gene-disrupted mutant of H. pylori UA802 could not be obtained,
      suggesting that this enzyme plays an essential role in the growth of this
      organism.

PMID- 9260936
TI  - A Salmonella typhimurium genetic locus which confers copper tolerance on copper
      sensitive mutants of Escherichia coli.
AB  - Three distinct clones from a Salmonella typhimurium genomic library were
      identified which suppressed the copper-sensitive (Cu(s)) phenotype of cutF
      mutants of Escherichia coli. One of these clones, pCUTFS2, also increased the
      copper tolerance of cutA, -C, and -E mutants, as well as that of a lipoprotein
      diacylglyceryl transferase (lgt) mutant of E. coli. Characterization of pCUTFS2
      revealed that the genes responsible for suppression of copper sensitivity (scs)
      reside on a 4.36-kb DNA fragment located near 25.4 min on the S. typhimurium
      genome. Sequence analysis of this fragment revealed four open reading frames
      (ORF120, ORF627, ORF207, and ORF168) that were organized into two operons. One
      operon consisted of a single gene, scsA (ORF120), whereas the other operon
      contained the genes scsB (ORF627), scsC (ORF207), and scsD (ORF168). Comparison
      of the deduced amino acid sequences of the predicted gene products showed that
      ScsB, ScsC, and ScsD have significant homology to thiol-disulfide interchange
      proteins (CutA2, DipZ, CycZ, and DsbD) from E. coli and Haemophilus influenzae,
      to an outer membrane protein (Com1) from Coxiella burnetii, and to thioredoxin
      and thioredoxin-like proteins, respectively. The two operons were subcloned on
      compatible plasmids, and complementation analyses indicated that all four
      proteins are required for the increased copper tolerance of E. coli mutants. In
      addition, the scs locus also restored lipoprotein modification in lgt mutants of
      E. coli. Sequence analyses of the S. typhimurium scs genes and adjacent DNAs
      revealed that the scs locus is flanked by genes with high homology to the cbpA
      (predicted curved DNA-binding protein) and agp (acid glucose phosphatase) genes
      of E. coli located at 22.90 min (1,062.07 kb) and 22.95 min (1,064.8 kb) of the
      E. coli chromosome, respectively. However, examination of the E. coli chromosome
      revealed that these genes are absent at this locus and no evidence has thus been
      obtained for the occurrence of the scs locus elsewhere on the genome.

PMID- 9260937
TI  - Polymerase C1 levels and poly(R-3-hydroxyalkanoate) synthesis in wild-type and
      recombinant Pseudomonas strains.
AB  - A functional antibody highly specific for polymerase C1 of Pseudomonas oleovorans
      GPo1 was raised and used to determine polymerase C1 levels in in vivo
      experiments. The polymerase C1 antibodies did not show a cross-reaction with
      polymerase C2 of P. oleovorans. In wild-type P. oleovorans GPo1 and Pseudomonas
      putida KT2442, amounts of 0.075 and 0.06% polymerase relative to total protein,
      respectively, were found. P. oleovorans GPo1(pGEc405), which contained additional
      copies of the polymerase C1-encoding gene under the control of its native
      promoter, contained 0.5% polymerase C1 relative to total protein. Polymerase C1
      reached 10% of total cell protein when the polymerase C1-encoding gene was
      overexpressed through the P(alk) promoter in P. oleovorans GPo1(pET702, pGEc74).
      Amounts of poly(R-3-hydroxyalkanoate) (PHA) increased significantly under non
      nitrogen-limiting conditions when additional polymerase C1 was expressed in P.
      oleovorans. Whereas P. oleovorans produced 34% (wt/wt) PHA under these
      conditions, a PHA level of 64% (wt/wt) could be reached for P. oleovorans
      GPo1(pGEc405) and a PHA level of 52% (wt/wt) could be reached for P. oleovorans
      GPo1(pET702, pGEc74) after induction, compared to a PHA level of 13% for the
      uninduced control. All recombinant Pseudomonas strains containing additional
      polymerase C1 showed small changes in their PHA composition. Larger amounts of 3
      hydroxyhexanoate monomer and smaller amounts of 3-hydroxyoctanoate and -decanoate
      were found compared to those of the wild type. Two different methods were
      developed to quantify rates of incorporation of new monomers into preexisting PHA
      granules. P. oleovorans GPo1 cells grown under nitrogen-limiting conditions
      showed growth stage-dependent incorporation rates. The highest PHA synthesis
      rates of 9.5 nmol of C8/C6 monomers/mg of cell dry weight (CDW)/min were found
      during the mid-stationary phase, which equals a rate of production of 80 g of
      PHA/kg of CDW/h.

PMID- 9260939
TI  - Nucleotide sequence and characterization of the cryptic Bacillus thuringiensis
      plasmid pGI3 reveal a new family of rolling circle replicons.
AB  - The complete nucleotide sequence of plasmid pGI3 from Bacillus thuringiensis
      subsp. thuringiensis H1.1. was obtained. Although this 11,365-bp molecule
      contained at least 11 putative open reading frames (ORFs), extensive database
      searches did not reveal any homologous sequences with the exception of ORF6,
      which displayed similarity to the largest ORF of pSTK1, a 1,883-bp cryptic
      plasmid isolated from Bacillus stearothermophilus. Deletion analysis to determine
      the pGI3 minimal replicon revealed that ORF6 is the rep gene. Replication
      occurred via a single-stranded DNA (ssDNA) intermediate, as demonstrated by S1
      treatment and Southern hybridization in nondenaturating conditions.
      Interestingly, however, no homology was found between the pGI3 (ORF6) and pSTK1
      (ORF3) rep genes and those from other single-stranded DNA plasmids, nor was there
      any DNA similarity to the double-strand origins of replication characterized so
      far, indicating that pGI3 and pSTK1 form another, new family of ssDNA plasmids.
      PCR analysis revealed that the pGI3 rep gene is largely distributed among B.
      thuringiensis strains but can also be found in B. cereus and B. mycoides strains,
      albeit at a lower frequency. Finally, segregation experiments performed with B.
      subtilis and B. thuringiensis showed that the pGI3 derivatives, including the
      minimal replicon, were segregationally stable at temperatures suitable for B.
      thuringiensis growth (<43 degrees C).

PMID- 9260940
TI  - Control of poly-beta-hydroxybutyrate synthase mediated by acetyl phosphate in
      cyanobacteria.
AB  - Poly-beta-hydroxybutyrate (PHB) synthesis in a cyanobacterium, Synechococcus sp.
      strain MA19, is controlled at the enzyme level and is dependent on the C/N
      balance in the culture medium. The control involves at least two enzymes. The
      first enzyme is PHB synthase. Little PHB synthase activity was detected in crude
      extracts from cells grown under nitrogen-sufficient conditions (MA19(+N)). The
      activity was detected exclusively in membrane fractions from nitrogen-deprived
      cells (MA19(-N)) under light but not dark conditions. The shift in the enzyme
      activity was insensitive to chloramphenicol, which suggests posttranslational
      activation. Acetyl phosphate activated PHB synthase in membrane fractions from
      MA19(+N). In vitro, the activation level of PHB synthase changed, depending on
      the concentration of acetyl phosphate. The second enzyme was
      phosphotransacetylase (EC 2.3.1.8), which catalyzes the conversion of acetyl
      coenzyme A (acetyl-CoA) to acetyl phosphate. The activity was detected in crude
      extracts from MA19(-N) but not in those from MA19(+N). The results suggested that
      intracellular acetyl phosphate concentration could be controlled, depending on
      C/N balance and intracellular acetyl-CoA concentration. Acetyl phosphate probably
      acts as a signal of C/N balance affecting PHB metabolism in MA19.

PMID- 9260938
TI  - The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase of Candida
      albicans is a surface antigen.
AB  - A lambda gt11 cDNA library from Candida albicans ATCC 26555 was screened by using
      pooled sera from two patients with systemic candidiasis and five neutropenic
      patients with high levels of anti-C. albicans immunoglobulin M antibodies. Seven
      clones were isolated from 60,000 recombinant phages. The most reactive one
      contained a 0.9-kb cDNA encoding a polypeptide immunoreactive only with sera from
      patients with systemic candidiasis. The whole gene was isolated from a genomic
      library by using the cDNA as a probe. The nucleotide sequence of the coding
      region showed homology (78 to 79%) to the Saccharomyces cerevisiae TDH1 to TDH3
      genes coding for glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and their
      amino acid sequences showed 76% identity; thus, this gene has been named C.
      albicans TDH1. A rabbit polyclonal antiserum against the purified cytosolic C.
      albicans GAPDH (polyclonal antibody [PAb] anti-CA-GAPDH) was used to identify the
      GAPDH in the beta-mercaptoethanol extracts containing cell wall moieties.
      Indirect immunofluorescence demonstrated the presence of GAPDH at the C. albicans
      cell surface, particularly on the blastoconidia. Semiquantitative flow cytometry
      analysis showed the sensitivity of this GAPDH form to trypsin and its resistance
      to be removed with 2 M NaCl or 2% sodium dodecyl sulfate. The decrease in
      fluorescence in the presence of soluble GAPDH indicates the specificity of the
      labelling. In addition, a dose-dependent GAPDH enzymatic activity was detected in
      intact blastoconidia and germ tube cells. This activity was reduced by
      pretreatment of the cells with trypsin, formaldehyde, and PAb anti-CA-GAPDH.
      These observations indicate that an immunogenic, enzymatically active cell wall
      associated form of the glycolytic enzyme GAPDH is found at the cell surface of C.
      albicans cells.

PMID- 9260941
TI  - Cloning and characterization of sulfite dehydrogenase, two c-type cytochromes,
      and a flavoprotein of Paracoccus denitrificans GB17: essential role of sulfite
      dehydrogenase in lithotrophic sulfur oxidation.
AB  - A 13-kb genomic region of Paracoccus dentrificans GB17 is involved in
      lithotrophic thiosulfate oxidation. Adjacent to the previously reported soxB gene
      (C. Wodara, S. Kostka, M. Egert, D. P. Kelly, and C. G. Friedrich, J. Bacteriol.
      176:6188-6191, 1994), 3.7 kb were sequenced. Sequence analysis revealed four
      additional open reading frames, soxCDEF. soxC coded for a 430-amino-acid
      polypeptide with an Mr of 47,339 that included a putative signal peptide of 40
      amino acids (Mr of 3,599) with a RR motif present in periplasmic proteins with
      complex redox centers. The mature soxC gene product exhibited high amino acid
      sequence similarity to the eukaryotic molybdoenzyme sulfite oxidase and to
      nitrate reductase. We constructed a mutant, GBsoxC delta, carrying an in-frame
      deletion in soxC which covered a region possibly coding for the molybdenum
      cofactor binding domain. GBsoxC delta was unable to grow lithoautotrophically
      with thiosulfate but grew well with nitrate as a nitrogen source or as an
      electron acceptor. Whole cells and cell extracts of mutant GBsoxC delta contained
      10% of the thiosulfate-oxidizing activity of the wild type. Only a marginal rate
      of sulfite-dependent cytochrome c reduction was observed from cell extracts of
      mutant GBsoxC delta. These results demonstrated that sulfite dehydrogenase was
      essential for growth with thiosulfate of P. dentrificans GB17. soxD coded for a
      periplasmic diheme c-type cytochrome of 384 amino acids (Mr of 39,983) containing
      a putative signal peptide with an Mr of 2,363. soxE coded for a periplasmic
      monoheme c-type cytochrome of 236 amino acids (Mr of 25,926) containing a
      putative signal peptide with an Mr of 1,833. SoxD and SoxE were highly identical
      to c-type cytochromes of P. denitrificans and other organisms. soxF revealed an
      incomplete open reading frame coding for a peptide of 247 amino acids with a
      putative signal peptide (Mr of 2,629). The deduced amino acid sequence of soxF
      was 47% identical and 70% similar to the sequence of the flavoprotein of
      flavocytochrome c of Chromatium vinosum, suggesting the involvement of the
      flavoprotein in thiosulfate oxidation of P. denitrificans GB17.

PMID- 9260942
TI  - Transcriptional control of the multiple catabolic pathways encoded on the TOL
      plasmid pWW53 of Pseudomonas putida MT53.
AB  - The TOL plasmid pWW53 encodes a catabolic pathway for the metabolism of toluene.
      It bears an upper-pathway operon for the oxidation of toluene to benzoate and a
      copy of the gene that encodes regulatory protein XylR. For metabolism of the
      aromatic carboxylic acid, it bears two functional homologous meta-pathway
      operons, together with two functional copies of the xylS regulatory gene (xylS1
      and xylS3). In cells growing in the absence of pathway substrates, no mRNA from
      upper- and meta-pathway operons were found; however, the xylR gene was expressed
      from two sigma70-dependent tandem promoters, and the xylS1 and the xylS3 genes
      were also expressed from their sigma70-dependent promoters, called Ps2 and Ps3,
      respectively. In cells grown in the presence of o-xylene, the XylR protein became
      active and stimulated transcription from the Pu promoter for the upper pathway.
      Expression from xylS1 but not from xylS3 was also stimulated by XylR; this was
      due to activation of transcription from the xylS1 Ps1 promoter, which is sigma54
      dependent, and the lack of effect on expression from the Ps2 sigma70-dependent
      promoter. As a result of overexpression of the xylS1 gene, the XylS1 protein was
      overproduced and activated transcription from Pm1 and Pm2. In cells growing on
      benzoate, the upper-pathway operon was not expressed, but both meta operons were
      expressed. Given that XylS1 but not XylS3 recognized benzoate as an effector,
      stimulation of transcription was found to be mediated by XylS1. This was
      confirmed with cloned meta-pathway promoters and regulators. When 3
      methylbenzoate was present in the medium, both meta operons were also expressed
      and stimulation of transcription was mediated by both XylS1 and XylS3, which both
      recognized 3-methylbenzoate as an effector.

PMID- 9260943
TI  - Evidence that part of a centromeric DNA region induces pseudohyphal growth in a
      dimorphic yeast, Candida maltosa.
AB  - We observed that a YCp-type vector having the centromeric DNA (CEN) sequence
      previously isolated from the genome, but not a YRp-type vector lacking the CEN
      sequence, induced pseudohyphal growth in a dimorphic fungi, Candida maltosa,
      which had been shown to be closely related to Candida albicans by phylogenetic
      analysis. Deletion analysis of the CEN sequence revealed that the intact CEN
      sequence was not required for the induction, but part of it, having partial
      centromeric activity, was enough for the induction. By screening the gene library
      of this yeast for the sequences which induced pseudohyphal growth, we isolated
      three different DNA fragments which also had part of the centromere-like
      sequence. Partial centromeric activity of these fragments was confirmed by three
      criteria: low copy number and high stability of the plasmids carrying these
      fragments and rearrangement at high frequency of the plasmid DNA with one of
      these fragments plus the CEN sequence. Furthermore, when the GGTAGCG sequence
      commonly found in one copy in each of these four sequences was mutated in the CEN
      sequence by site-directed mutagenesis, both partial centromeric activity and
      pseudohyphal growth-inducing activity of the CEN sequence were lost. These
      results indicated that part of CEN region with partial centromeric activity
      induces pseudohyphal growth in C. maltosa. It is suggested that some cellular
      components which interact with the sequence containing GGTAGCG required for
      centromeric activity are involved in the regulation of the transition between
      yeast forms and pseudohyphal forms of the cells.

PMID- 9260944
TI  - Characterization by electron paramagnetic resonance of the role of the
      Escherichia coli nitrate reductase (NarGHI) iron-sulfur clusters in electron
      transfer to nitrate and identification of a semiquinone radical intermediate.
AB  - We have used Escherichia coli cytoplasmic membrane preparations enriched in wild
      type and mutant (NarH-C16A and NarH-C263A) nitrate reductase (NarGHI) to study
      the role of the [Fe-S] clusters of this enzyme in electron transfer from quinol
      to nitrate. The spectrum of dithionite-reduced membrane bound NarGHI has major
      features comprising peaks at g = 2.04 and g = 1.98, a peak-trough at g = 1.95,
      and a trough at g = 1.87. The oxidized spectrum of NarGHI in membranes comprises
      an axial [3Fe-4S] cluster spectrum with a peak at g = 2.02 (g(z)) and a peak
      trough at g = 1.99 (g(xy)). We have shown that in two site-directed mutants of
      NarGHI which lack the highest potential [4Fe-4S] cluster (B. Guigliarelli, A.
      Magalon, P. Asso, P. Bertrand, C. Frixon, G. Giordano, and F. Blasco,
      Biochemistry 35:4828-4836, 1996), NarH-C16A and NarH-C263A, oxidation of the NarH
      [Fe-S] clusters is inhibited compared to the wild type. During enzyme turnover in
      the mutant enzymes, a distinct 2-n-heptyl-4-hydroxyquinoline-N-oxide-sensitive
      semiquinone radical species which may be located between the hemes of NarI and
      the [Fe-S] clusters of NarH is observed. Overall, these studies indicate (i) the
      importance of the highest-potential [4Fe-4S] cluster in electron transfer from
      NarH to the molybdenum cofactor of NarG and (ii) that a semiquinone radical
      species is an important intermediate in electron transfer from quinol to nitrate.

PMID- 9260945
TI  - Overexpression of the D-alanine racemase gene confers resistance to D-cycloserine
      in Mycobacterium smegmatis.
AB  - D-Cycloserine is an effective second-line drug against Mycobacterium avium and
      Mycobacterium tuberculosis. To analyze the genetic determinants of D-cycloserine
      resistance in mycobacteria, a library of a resistant Mycobacterium smegmatis
      mutant was constructed. A resistant clone harboring a recombinant plasmid with a
      3.1-kb insert that contained the glutamate decarboxylase (gadA) and D-alanine
      racemase (alrA) genes was identified. Subcloning experiments demonstrated that
      alrA was necessary and sufficient to confer a D-cycloserine resistance phenotype.
      The D-alanine racemase activities of wild-type and recombinant M. smegmatis
      strains were inhibited by D-cycloserine in a concentration-dependent manner. The
      D-cycloserine resistance phenotype in the recombinant clone was due to the
      overexpression of the wild-type alrA gene in a multicopy vector. Analysis of a
      spontaneous resistant mutant also demonstrated overproduction of wild-type AlrA
      enzyme. Nucleotide sequence analysis of the overproducing mutant revealed a
      single transversion (G-->T) at the alrA promoter, which resulted in elevated beta
      galactosidase reporter gene expression. Furthermore, transformants of
      Mycobacterium intracellulare and Mycobacterium bovis BCG carrying the M.
      smegmatis wild-type alrA gene in a multicopy vector were resistant to D
      cycloserine, suggesting that AlrA overproduction is a potential mechanism of D
      cycloserine resistance in clinical isolates of M. tuberculosis and other
      pathogenic mycobacteria. In conclusion, these results show that one of the
      mechanisms of D-cycloserine resistance in M. smegmatis involves the
      overexpression of the alrA gene due to a promoter-up mutation.

PMID- 9260946
TI  - PcaK, a high-affinity permease for the aromatic compounds 4-hydroxybenzoate and
      protocatechuate from Pseudomonas putida.
AB  - PcaK is a transporter and chemoreceptor protein from Pseudomonas putida that is
      encoded as part of the beta-ketoadipate pathway regulon for aromatic acid
      degradation. When expressed in Escherichia coli, PcaK was localized to the
      membrane and catalyzed the accumulation of two aromatic substrates, 4
      hydroxybenzoate and protocatechuate, against a concentration gradient. Benzoate
      inhibited 4-hydroxybenzoate uptake but was not a substrate for PcaK-catalyzed
      transport. A P. putida pcaK mutant was defective in its ability to accumulate
      micromolar amounts of 4-hydroxybenzoate and protocatechuate. The mutant was also
      impaired in growth on millimolar concentrations of these aromatic acids. In
      contrast, the pcaK mutant grew at wild-type rates on benzoate. The Vmax for
      uptake of 4-hydroxybenzoate was at least 25 nmol/min/mg of protein, and the Km
      was 6 microM. PcaK-mediated transport is energized by the proton motive force.
      These results show that although aromatic acids in the undissociated (uncharged)
      form can diffuse across bacterial membranes, high-specificity active transport
      systems probably also contribute to the ability of bacteria to grow on the
      micromolar concentrations of these compounds that are typically present in soil.
      A variety of aromatic molecules, including naturally occurring lignin derivatives
      and xenobiotics, are metabolized by bacteria and may be substrates for transport
      proteins. The characterization of PcaK provides a foundation for understanding
      active transport as a critical step in the metabolism of aromatic carbon sources.

PMID- 9260948
TI  - Gene cloning and expression and characterization of a toxin-sensitive protein
      phosphatase from the methanogenic archaeon Methanosarcina thermophila TM-1.
AB  - With oligonucleotides modelled after conserved regions within the protein
      serine/threonine phosphatases (PPs) of the PP1/2A/2B superfamily, the gene for
      the archaeal protein phosphatase PP1-arch2 was identified, cloned, and sequenced
      from the methanogenic archaeon Methanosarcina thermophila TM-1. The DNA-derived
      amino acid sequence of PP1-arch2 exhibited a high degree of sequence identity, 27
      to 31%, with members of the PP1/2A/2B superfamily such as PP1-arch1 from
      Sulfolobus solfataricus, PP1alpha from rats, PP2A from Saccharomyces cerevisiae,
      and PP2B from humans. The activity of the recombinant PP1-arch2 was sensitive to
      several naturally occurring microbial toxins known to potently inhibit eucaryal
      PP1 and PP2A, including microcystin-LR, okadaic acid, tautomycin, and calyculin
      A.

PMID- 9260947
TI  - Characterization of a transposon Tn916-generated mutant of Haemophilus ducreyi
      35000 defective in lipooligosaccharide biosynthesis.
AB  - To define the role of the surface lipooligosaccharide (LOS) of Haemophilus
      ducreyi in the pathogenesis of chancroid, Tn916 mutants of H. ducreyi 35000
      defective in expression of the murine monoclonal antibody (MAb) 3F11 epitope on
      H. ducreyi LOS were identified by immunologic screening. One mutant, designated
      1381, has an LOS which lacks the MAb 3F11 epitope and migrates with an increased
      mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The gene
      disrupted by the Tn916 element in strain 1381 was identified by cloning the
      sequences flanking the Tn916 element. The sequences were then used to probe a
      lambda DASHII genomic library. In strain 1381, Tn916 interrupts a gene which
      encodes an open reading frame (ORF) with an Mr of 40,246. This ORF has homology
      to the product of the rfaK gene of Escherichia coli. The major LOS glycoform
      produced by strain 1381 was analyzed by using a combination of mass spectrometry,
      linkage and composition analysis, and 1H nuclear magnetic resonance spectroscopy.
      The major LOS species was found to terminate in a single glucose attached to the
      heptose (L-glycero-D-manno-heptose, or Hep) trisaccharide core. In the wild-type
      strain 35000, glucose serves as the acceptor for the addition of the D-glycero-D
      manno-heptose (or DDHep), which extends to form the mature branch of the H.
      ducreyi LOS. This mature oligosaccharide is in turn partially capped by the
      addition of sialic acid (NeuAc), i.e., NeuAc2 alpha-->3Gal beta1-->4GlcNAc beta1-
      >3Gal beta1-->4DDHep alpha1-->6Glc beta1 (W. Melaugh et al., Biochemistry
      33:13070-13078, 1994). Since this LOS terminates prior to the addition of the
      branch DD-heptose, this gene is likely to encode the D-glycero-D-manno
      heptosyltransferase. Strain 1381 exhibits a significant reduction in adherence to
      and invasion of primary human keratinocytes. This defect was complemented by the
      cloned heptosyltransferase gene, indicating that the terminal portion of the LOS
      oligosaccharide plays an important role in adherence to human keratinocytes.

PMID- 9260949
TI  - Tromp1, a putative rare outer membrane protein, is anchored by an uncleaved
      signal sequence to the Treponema pallidum cytoplasmic membrane.
AB  - Treponema pallidum rare outer membrane protein 1 (Tromp1) has extensive sequence
      homology with substrate-binding proteins of ATP-binding cassette transporters.
      Because such proteins typically are periplasmic or cytoplasmic membrane
      associated, experiments were conducted to clarify Tromp1's physicochemical
      properties and cellular location in T. pallidum. Comparison of the sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis mobilities of (i) native Tromp1 and
      Tromp1 synthesized by coupled in vitro transcription-translation and (ii) native
      Tromp1 and recombinant Tromp1 lacking the N-terminal signal sequence revealed
      that the native protein is not processed. Other studies demonstrated that
      recombinant Tromp1 lacks three basic porin-like properties: (i) the ability to
      form aqueous channels in liposomes which permit the influx of small hydrophilic
      solutes, (ii) an extensive beta-sheet secondary structure, and (iii)
      amphiphilicity. Subsurface localization of native Tromp1 was demonstrated by
      immunofluorescence analysis of treponemes encapsulated in gel microdroplets,
      while opsonization assays failed to detect surface-exposed Tromp1. Incubation of
      motile treponemes with 3-(trifluoromethyl)-3-(m-[125I]iodophenyl)-diazarine, a
      photoactivatable, lipophilic probe, also did not result in the detection of
      Tromp1 within the outer membranes of intact treponemes but, instead, resulted in
      the labeling of a basic 30.5-kDa presumptive outer membrane protein. Finally,
      analysis of fractionated treponemes revealed that native Tromp1 is associated
      predominantly with cell cylinders. These findings comprise a body of evidence
      that Tromp1 actually is anchored by an uncleaved signal sequence to the
      periplasmic face of the T. pallidum cytoplasmic membrane, where it likely
      subserves a transport-related function.

PMID- 9260950
TI  - Rhizobium sp. strain NGR234 NodZ protein is a fucosyltransferase.
AB  - Rhizobium sp. strain NGR234 produces a large family of lipochitooligosaccharide
      Nod factors carrying specific substituents. Among them are 3-O- (or 4-O-) and 6-O
      carbamoyl groups, an N-methyl group, and a 2-O-methylfucose residue which may
      bear either 3-O-sulfate or 4-O-acetyl substitutions. Investigations on the
      genetic control of host specificity revealed a number of loci which directly
      affect Nod factor structure. Here we show that insertion and frameshift mutations
      in the nodZ gene abolish fucosylation of Nod factors. In vitro assays using GDP-L
      fucose as the fucose donor show that fucosyltransferase activity is associated
      with the nodZ gene product (NodZ). NodZ is located in the soluble protein
      fraction of NGR234 cells. Together with extra copies of the nodD1 gene, the nodZ
      gene and its associated nod box were introduced into ANU265, which is NGR234
      cured of the symbiotic plasmid. Crude extracts of this transconjugant possess
      fucosyltransferase activity. Fusion of a His6 tag to the NodZ protein expressed
      in Escherichia coli yielded a protein able to fucosylate both nonfucosylated
      NodNGR factors and oligomers of chitin. NodZ is inactive on monomeric N-acetyl-D
      glucosamine and on desulfated Rhizobium meliloti Nod factors. Kinetic analyses
      showed that the NodZ protein is more active on oligomers of chitin than on
      nonfucosylated NodNGR factors. Pentameric chitin is the preferred substrate.
      These data suggest that fucosylation occurs before acylation of the Nod factors.

PMID- 9260951
TI  - Domain-swapping analysis of FtsI, FtsL, and FtsQ, bitopic membrane proteins
      essential for cell division in Escherichia coli.
AB  - FtsI, FtsL, and FtsQ are three membrane proteins required for assembly of the
      division septum in the bacterium Escherichia coli. Cells lacking any of these
      three proteins form long, aseptate filaments that eventually lyse. FtsI, FtsL,
      and FtsQ are not homologous but have similar overall structures: a small
      cytoplasmic domain, a single membrane-spanning segment (MSS), and a large
      periplasmic domain that probably encodes the primary functional activities of
      these proteins. The periplasmic domain of FtsI catalyzes transpeptidation and is
      involved in the synthesis of septal peptidoglycan. The precise functions of FtsL
      and FtsQ are not known. To ask whether the cytoplasmic domain and MSS of each
      protein serve only as a membrane anchor or have instead a more sophisticated
      function, we have used molecular genetic techniques to swap these domains among
      the three Fts proteins and one membrane protein not involved in cell division,
      MalF. In the cases of FtsI and FtsL, replacement of the cytoplasmic domain and/or
      MSS resulted in the loss of the ability to support cell division. For FtsQ, MSS
      swaps supported cell division but cytoplasmic domain swaps did not. We discuss
      several potential interpretations of these results, including that the essential
      domains of FtsI, FtsL, and FtsQ have a role in regulating the localization and/or
      activity of these proteins to ensure that septum formation occurs at the right
      place in the cell and at the right time during the division cycle.

PMID- 9260952
TI  - Putative channel components for the fast-rotating sodium-driven flagellar motor
      of a marine bacterium.
AB  - The polar flagellum of Vibrio alginolyticus rotates remarkably fast (up to 1,700
      revolutions per second) by using a motor driven by sodium ions. Two genes, motX
      and motY, for the sodium-driven flagellar motor have been identified in marine
      bacteria, Vibrio parahaemolyticus and V. alginolyticus. They have no similarity
      to the genes for proton-driven motors, motA and motB, whose products constitute a
      proton channel. MotX was proposed to be a component of a sodium channel. Here we
      identified additional sodium motor genes, pomA and pomB, in V. alginolyticus.
      Unexpectedly, PomA and PomB have similarities to MotA and MotB, respectively,
      especially in the predicted transmembrane regions. These results suggest that
      PomA and PomB may be sodium-conducting channel components of the sodium-driven
      motor and that the motor part consists of the products of at least four genes,
      pomA, pomB, motX, and motY. Furthermore, swimming speed was controlled by the
      expression level of the pomA gene, suggesting that newly synthesized PomA
      proteins, which are components of a force-generating unit, were successively
      integrated into the defective motor complexes. These findings imply that Na+
      driven flagellar motors may have similar structure and function as proton-driven
      motors, but with some interesting differences as well, and it is possible to
      compare and study the coupling mechanisms of the sodium and proton ion flux for
      the force generation.

PMID- 9260953
TI  - Induction of the heat shock protein ClpB affects cold acclimation in the
      cyanobacterium Synechococcus sp. strain PCC 7942.
AB  - The heat shock protein ClpB is essential for acquired thermotolerance in
      cyanobacteria and eukaryotes and belongs to a diverse group of polypeptides which
      function as molecular chaperones. In this study we show that ClpB is also
      strongly induced during moderate cold stress in the unicellular cyanobacterium
      Synechococcus sp. strain PCC 7942. A fivefold increase in ClpB (92 kDa) content
      occurred when cells were acclimated to 25 degrees C over 24 h after being shifted
      from the optimal growth temperature of 37 degrees C. A corresponding increase
      occurred for the smaller ClpB' (78 kDa), which arises from a second translational
      start within the clpB gene of prokaryotes. Shifts to more extreme cold (i.e., 20
      and 15 degrees C) progressively decreased the level of ClpB induction, presumably
      due to retardation of protein synthesis within this relatively cold-sensitive
      strain. Inactivation of clpB in Synechococcus sp. increased the extent of
      inhibition of photosynthesis upon the shift to 25 degrees C and markedly reduced
      the mutant's ability to acclimate to the new temperature regime, with a threefold
      drop in growth rate. Furthermore, around 30% fewer delta clpB cells survived the
      shift to 25 degrees C after 24 h compared to the wild type, and more of the
      mutant cells were also arrested during cell division at 25 degrees C, remaining
      attached after septum formation. Development of a cold thermotolerance assay
      based on cell survival clearly demonstrated that wild-type cells could acquire
      substantial resistance to the nonpermissive temperature of 15 degrees C by being
      pre-exposed to 25 degrees C. The same level of cold thermotolerance, however,
      occurred in the delta clpB strain, indicating ClpB induction is not necessary for
      this form of thermal resistance in Synechococcus spp. Overall, our results
      demonstrate that the induction of ClpB contributes significantly to the
      acclimation process of cyanobacteria to permissive low temperatures.

PMID- 9260954
TI  - Identification and analysis of a gene encoding L-2,4-diaminobutyrate:2
      ketoglutarate 4-aminotransferase involved in the 1,3-diaminopropane production
      pathway in Acinetobacter baumannii.
AB  - The ca. 2.2-kbp region upstream of the ddc gene encoding L-2,4-diaminobutyrate
      decarboxylase in Acinetobacter baumannii was sequenced and found to contain
      another open reading frame of 1,338 nucleotides encoding a protein with a deduced
      molecular mass of 47,423 Da. Analysis of the homologies observed from the deduced
      amino acid sequence indicated that the gene product is an enzyme belonging to
      subgroup II of the aminotransferases. This was first verified when examination of
      the crude extracts from Escherichia coli transformants led to detection of a
      novel aminotransferase activity catalyzing the following reversible reactions: L
      2,4-diaminobutyric acid + 2-ketoglutaric acid<-->L-glutamic acid + L-aspartic
      beta-semialdehyde. Further confirmation was obtained when the gene was
      overexpressed in E. coli and the corresponding protein was purified to
      homogeneity. It catalyzed the same reactions and its N-terminal amino acid
      sequence was consistent with that deduced from the nucleotide sequence.
      Therefore, the gene and its product were named dat and L-2,4-diaminobutyrate:2
      ketoglutarate 4-aminotransferase (DABA AT), respectively. Feeding experiments of
      A. baumannii with L-[U-14C]aspartic acid resulted in the incorporation of the
      label into 1,3-diaminopropane. Apparent homologs of dat and DABA AT were detected
      in other Acinetobacter species by PCR amplification and Western blotting. These
      results indicate that the dat gene (as well as the ddc gene) participates in the
      synthesis of 1,3-diaminopropane, the only diamine found in this genus. However,
      the biological role, if one exists, of 1,3-diaminopropane synthesis is unknown.

PMID- 9260955
TI  - Growth-phase-dependent expression of cspD, encoding a member of the CspA family
      in Escherichia coli.
AB  - The cspD gene of Escherichia coli encodes a protein of high sequence similarity
      with the cold shock protein CspA, but cspD expression is not induced by cold
      shock. In this study, we analyzed the regulation of cspD gene expression. By
      using a cspD-lacZ fusion and primer extension analysis, the expression of cspD
      was found to be dramatically induced by stationary-phase growth. However, this
      induction does not depend on the stationary-phase sigma factor sigmaS. Moreover,
      the expression of cspD is inversely dependent on growth rates and induced upon
      glucose starvation. Using a (p)ppGpp-depleted strain, we found that (p)ppGpp is
      one of the positive factors for the regulation of cspD expression.

PMID- 9260956
TI  - Cloning and characterization of the gene (farA) encoding the receptor for an
      extracellular regulatory factor (IM-2) from Streptomyces sp. strain FRI-5.
AB  - IM-2 is a butyrolactone autoregulator that controls production of blue pigment
      and nucleoside antibiotics in Streptomyces sp. strain FRI-5. An IM-2-specific
      receptor gene, farA, was cloned from strain FRI-5, and nucleotide sequencing
      revealed that the farA gene consists of 666 bp encoding a 221-amino-acid protein
      of 24.3 kDa with an NH2-terminal amino acid sequence identical to that of
      purified native receptor. Another gene, farX, encoding a homolog of AfsA of
      Streptomyces griseus, was present upstream of farA. The monocistronic nature of
      the farA transcript was shown by Northern blot hybridization, and the transcript
      level increased upon addition of IM-2. Recombinant FarA expressed in and purified
      from E. coli showed clear ligand specificity toward IM-2, with a dissociation
      constant (Kd) for [3H]IM-2-C5 of 18.2 nM. FarA showed high overall homology to
      BarA (virginiae butanolide receptor from S. virginiae) and ArpA (A-factor
      receptor from S. griseus). Sequence alignment of the three receptor proteins
      revealed that the NH2-terminal region containing a helix-turn-helix DNA binding
      motif was highly conserved. The DNA binding motif is common in procaryotic
      repressors of the TetR family, suggesting that all the Streptomyces autoregulator
      receptors may act as transcriptional repressors.

PMID- 9260957
TI  - Transcriptional and mutational analyses of the rpoN operon in Caulobacter
      crescentus.
AB  - The alternative sigma factor sigma54 is required for the biogenesis of both the
      flagellum and the stalk in Caulobacter crescentus. The DNA sequence downstream of
      the sigma54 gene (rpoN) has been determined, revealing three open reading frames
      (ORFs) encoding peptides of 203, 208, and 159 amino acids. ORF208 and ORF159 are
      homologous to ORFs found downstream of rpoN in other microorganisms. The
      organization of this region in C. crescentus is similar to that in other
      bacteria, with the exception of an additional ORF, ORF203, immediately downstream
      from rpoN. There is a single temporally regulated promoter that drives the
      expression of both rpoN and ORF203. Promoter probe analysis indicates the
      presence of another promoter downstream from ORF203 which exhibits a temporal
      control that is different from that of the rpoN promoter. Mutational analysis was
      used to address the function of the proteins encoded by these three downstream
      ORFs. The mutations have no effect on the transcription of previously known
      sigma54-dependent flagellar promoters except for a slight effect of an ORF159
      mutation on transcription of fljK.

PMID- 9260958
TI  - The resolvase/invertase domain of the site-specific recombinase TnpX is
      functional and recognizes a target sequence that resembles the junction of the
      circular form of the Clostridium perfringens transposon Tn4451.
AB  - Tn4451 is a 6.3-kb chloramphenicol resistance transposon from Clostridium
      perfringens and is found on the conjugative plasmid pIP401. The element undergoes
      spontaneous excision from multicopy plasmids in Escherichia coli and C.
      perfringens and conjugative excision from pIP401 in C. perfringens. Tn4451 is
      excised as a circular molecule which is probably the transposition intermediate.
      Excision of Tn4451 is dependent upon the site-specific recombinase TnpX, which
      contains potential motifs associated with both the resolvase/invertase and
      integrase families of recombinases. Site-directed mutagenesis of conserved amino
      acid residues within these domains was used to show that the resolvase/invertase
      domain was essential for TnpX-mediated excision of Tn4451 from multicopy plasmids
      in E. coli. An analysis of Tn4451 target sites revealed that the transposition
      process showed target site specificity. The Tn4451 target sequence resembled the
      junction of the circular form, and insertion occurred at a GA dinucleotide.
      Tn4451 insertions were flanked by directly repeated GA dinucleotides, and there
      was also a GA at the junction of the circular form, where the left and right
      termini of Tn4451 were fused. We propose a model for Tn4451 excision and
      insertion in which the resolvase/invertase domain of TnpX introduces 2-bp
      staggered cuts at these GA dinucleotides. Analysis of Tn4451 derivatives with
      altered GA dinucleotides provided experimental evidence to support the model.

PMID- 9260959
TI  - A novel alternate anaplerotic pathway to the glyoxylate cycle in streptomycetes.
AB  - ccr encoding crotonyl coenzyme A (CoA) reductase (CCR), which catalyzes the
      conversion of crotonyl-CoA to butyryl-CoA in the presence of NADPH, was
      previously cloned from Streptomyces collinus. We now report that a complete open
      reading frame, designated meaA, is located downstream from ccr. The predicted
      gene product showed 35% identity with methylmalonyl-CoA mutases from various
      sources. In addition, the predicted amino acid sequences of S. collinus ccr and
      meaA exhibit strong similarity to that of adhA (43% identity), a putative alcohol
      dehydrogenase gene, and meaA (62% identity) of Methylobacterium extorquens,
      respectively. Both adhA and meaA are involved in the assimilation of C1 and C2
      compounds in an unknown pathway in the isocitrate lyase (ICL)-negative
      Methylobacterium. We have demonstrated that S. collinus can grow with acetate as
      its sole carbon source even though there is no detectable ICL, suggesting that in
      this organism ccr and meaA may also be involved in a pathway for the assimilation
      of C2 compounds. Previous studies with streptomycetes provided a precedent for a
      pathway that initiates with the condensation of two acetyl-CoA molecules to form
      butyryl-CoA, which is then transformed to succinyl-CoA with two separate CoB12
      mediated rearrangements and a series of oxidations. The biological functions of
      ccr and meaA in this process were investigated by gene disruption. A ccr-blocked
      mutant showed no detectable crotonyl-CoA reductase activity and, compared to the
      wild-type strain, exhibited dramatically reduced growth when acetate was the sole
      carbon source. An meaA-blocked mutant also exhibited reduced growth on acetate.
      However, both methylmalonyl-CoA mutase and isobutyryl-CoA mutase, which catalyze
      the two CoB12-dependent rearrangements in this proposed pathway, were shown to be
      present in the meaA-blocked mutant. These results suggested that both ccr and
      meaA are involved in a novel pathway for the growth of S. collinus when acetate
      is its sole carbon source.

PMID- 9260960
TI  - D-erythro-neopterin biosynthesis in the methanogenic archaea Methanococcus
      thermophila and Methanobacterium thermoautotrophicum deltaH.
AB  - The steps in the biosynthetic transformation of GTP to 7,8-dihydro-D-erythro
      neopterin (H2neopterin), the precursor to the modified folates found in the
      methanogenic archaea, has been elucidated for the first time in two members of
      the domain Archaea. In Methanococcus thermophila and Methanobacterium
      thermoautotrophicum deltaH, it has been demonstrated that H2neopterin 2':3'
      cyclic phosphate is an intermediate in this conversion. In addition, the
      formation of the pterin ring of the H2neopterin 2':3'-cyclic phosphate is
      catalyzed not by a single enzyme, as is known to occur with GTP cyclohydrolase I
      in the Eucarya and Bacteria, but rather by two or more enzymes. A 2,4,5-triamino
      4(3H)-pyrimidinone-containing molecule, most likely 2,5-diamino-6-ribosylamino
      4(3H)-pyrimidinone 5'-triphosphate, has been identified as an intermediate in the
      formation of the H2neopterin 2':3'-cyclic phosphate. Synthetic H2neopterin 2':3'
      cyclic phosphate was found to be readily hydrolyzed by cell extracts of M.
      thermophila via the H2neopterin 3'-phosphate to H2neopterin, a known precursor to
      the pterin portion of methanopterin.

PMID- 9260961
TI  - Subunit and amino acid interactions in the Escherichia coli mannitol permease: a
      functional complementation study of coexpressed mutant permease proteins.
AB  - Mannitol-specific enzyme II, or mannitol permease, of the phosphoenolpyruvate
      dependent carbohydrate phosphotransferase system of Escherichia coli carries out
      the transport and phosphorylation of D-mannitol and is most active as a dimer in
      the membrane. We recently reported the importance of a glutamate residue at
      position 257 in the binding and transport of mannitol by this protein (C.
      Saraceni-Richards and G. R. Jacobson, J. Bacteriol. 179:1135-1142, 1997).
      Replacing Glu-257 with alanine (E257A) or glutamine (E257Q) eliminated detectable
      mannitol binding and transport by the permease. In contrast, an E257D mutant
      protein was able to bind and phosphorylate mannitol in a manner similar to that
      of the wild-type protein but was severely defective in mannitol uptake. In this
      study, we have coexpressed proteins containing mutations at position 257 with
      other inactive permeases containing mutations in each of the three domains of
      this protein. Activities of any active heterodimers resulting from this
      coexpression were measured. The results show that various inactive mutant
      permease proteins can complement proteins containing mutations at position 257.
      In addition, we show that both Glu at position 257 and His at position 195, both
      of which are in the membrane-bound C domain of the protein, must be on the same
      subunit of a permease dimer in order for efficient mannitol phosphorylation and
      uptake to occur. The results also suggest that mannitol bound to the opposite
      subunit within a permease heterodimer can be phosphorylated by the subunit
      containing the E257A mutation (which cannot bind mannitol) and support a model in
      which there are separate binding sites on each subunit within a permease dimer.
      Finally, we provide evidence from these studies that high-affinity mannitol
      binding is necessary for efficient transport by mannitol permease.

PMID- 9260963
TI  - Protection of DNA during oxidative stress by the nonspecific DNA-binding protein
      Dps.
AB  - Reactive oxygen species can damage most cellular components, but DNA appears to
      be the most sensitive target of these agents. Here we present the first evidence
      of DNA protection against the toxic and mutagenic effects of oxidative damage in
      metabolically active cells: direct protection of DNA by Dps, an inducible
      nonspecific DNA-binding protein from Escherichia coli. We demonstrate that in a
      recA-deficient strain, expression of Dps from an inducible promoter prior to
      hydrogen peroxide challenge increases survival and reduces the number of
      chromosomal single-strand breaks. dps mutants exhibit increased levels of the G x
      C-->T x A mutations characteristic of oxidative damage after treatment with
      hydrogen peroxide. In addition, expression of Dps from the inducible plasmid
      reduces the frequency of spontaneous G x C-->T x A and A x T-->T x A mutations
      and can partially suppress the mutator phenotype of mutM (fpg) and mutY alleles.
      In a purified in vitro system, Dps reduces the number of DNA single-strand breaks
      and Fpg-sensitive sites introduced by hydrogen peroxide treatment, indicating
      that the protection observed in vivo is a direct effect of DNA binding by Dps.
      The widespread conservation of Dps homologs among prokaryotes suggests that this
      may be a general strategy for coping with oxidative stress.

PMID- 9260962
TI  - Role of mga in growth phase regulation of virulence genes of the group A
      streptococcus.
AB  - To determine whether growth phase affects the expression of mga and other
      virulence-associated genes in the group A streptococcus (GAS), total RNA was
      isolated from the serotype M6 GAS strain JRS4 at different phases of growth and
      transcript levels were quantitated by hybridization with radiolabeled DNA probes.
      Expression of mga (which encodes a multiple gene regulator) and the Mga-regulated
      genes emm (which encodes M protein) and scpA (which encodes a complement C5a
      peptidase) was found to be maximal in exponential phase and shut off as the
      bacteria entered stationary phase, while the housekeeping genes recA and rpsL
      showed constant transcript levels over the same period of growth. Expression of
      mga from a foreign phage promoter in a mga-deleted GAS strain (JRS519) altered
      the wild-type growth phase-dependent transcription profile seen for emm and scpA,
      as well as for mga. Therefore, the temporal control of mga expression requires
      its upstream promoter region, and the subsequent growth phase regulation of emm
      and scpA is Mga dependent. A number of putative virulence genes in JRS4 were
      shown not to require Mga for their expression, although several exhibited growth
      phase-dependent regulation that was similar to mga, i.e., slo (which encodes
      streptolysin O) and plr (encoding the plasmin receptor/glyceraldehyde-3-phosphate
      dehydrogenase). Still others showed a markedly different pattern of expression
      (the genes for the superantigen toxins MF and SpeC). These results suggest the
      existence of complex levels of global regulation sensitive to growth phase that
      directly control the expression of virulence genes and mga in GAS.

PMID- 9260964
TI  - The IncP plasmid-encoded cell envelope-associated DNA transfer complex increases
      cell permeability.
AB  - IncP-type plasmids are broad-host-range conjugative plasmids. DNA translocation
      requires DNA transfer-replication functions and additional factors required for
      mating pair formation (Mpf). The Mpf system is located in the cell membranes and
      is responsible for DNA transport from the donor to the recipient. The Mpf complex
      acts as a receptor for IncP-specific phages such as PRD1. In this investigation,
      we quantify the Mpf complexes on the cell surface by a phage receptor saturation
      technique. Electrochemical measurements are used to show that the Mpf complex
      increases cell envelope permeability to lipophilic compounds and ATP. In addition
      it reduces the ability of the cells to accumulate K+. However, the Mpf complex
      does not dissipate the membrane voltage. The Mpf complex is rapidly disassembled
      when intracellular ATP concentration is decreased, as measured by a PRD1
      adsorption assay.

PMID- 9260965
TI  - Changes in host cell energetics in response to bacteriophage PRD1 DNA entry.
AB  - Double-stranded DNA bacteriophage PRD1 infects a variety of gram-negative
      bacteria harboring an IncP-type conjugative plasmid. The plasmid codes for the
      DNA transfer phage receptor complex in the cell envelope. Our goal was, by using
      a collection of mutant phage particles for which the variables are the DNA
      content and/or the presence of the receptor-binding protein, to obtain
      information on the energy requirements for DNA entry as well as on alterations in
      the cellular energetics taking place during the first stages of infection. We
      studied the fluxes of tetraphenylphosphonium (TPP+), phenyldicarbaundecaborane
      (PCB-), and K+ ions as well as ATP through the envelope of Salmonella typhimurium
      cells. The final level of the membrane voltage (delta psi) indicator TPP+
      accumulated by the infected cells exceeds the initial level before the infection.
      Besides the effects on TPP+ accumulation, PRD1 induces the leakage of ATP and K+
      from the cytosol. All these events were induced only by DNA-containing infectious
      particles and were cellular ATP and delta psi dependent. PRD1-caused changes in
      delta psi and in PCB- binding differ considerably from those observed in other
      bacteriophage infections studied. These results are in accordance with the
      presence of a specific channel engaged in phage PRD1 DNA transport.

PMID- 9260966
TI  - Mutations that render the promoter of the histidine operon of Salmonella
      typhimurium insensitive to nutrient-rich medium repression and amino acid
      downshift.
AB  - The effects of mutations in the promoter of the histidine operon of Salmonella
      typhimurium were examined in vivo. The wild-type chromosomal copy of the his
      promoter was replaced with mutations in the -10 hexamer sequence and in the
      region between the -10 hexamer and the transcriptional start point-termed the
      discriminator sequence. The substitutions were performed with a phage M13 allele
      replacement system. Expression of the his operon is known to correlate with
      levels of guanosine 5',3'-bispyrophosphate (ppGpp) in vivo. Strains containing
      either the wild-type his promoter or his promoter mutations were grown in both
      nutrient-rich and minimal media under steady-state conditions known to alter
      intracellular levels of ppGpp in a predictable way. The effect of the presence or
      absence of the his attenuator was assessed under these conditions as well.
      Expression of the his operon was studied by measuring the differential rate of
      beta-galactosidase synthesis with a his-lac transcriptional fusion. Regulation of
      the his operon in the promoter mutants was also studied under conditions of a
      transient amino acid downshift induced by the addition of serine hydroxamate to
      cultures growing in nutrient-rich medium. These growth conditions cause elevated
      levels of ppGpp. The results provide physiological confirmation of previous
      evidence obtained with a coupled transcription-translation system in vitro which
      indicated that ppGpp regulates interaction of RNA polymerase at the his promoter.
      More specifically, the in vivo evidence shows that the region of the his promoter
      that includes the -10 hexamer and discriminator sequences is the target at which
      ppGpp stimulates transcription.

PMID- 9260967
TI  - Characterization of Escherichia coli strains with gapA and gapB genes deleted.
AB  - We obtained a series of Escherichia coli strains in which gapA, gapB, or both had
      been deleted. Delta gapA strains do not revert on glucose, while delta gapB
      strains grow on glycerol or glucose. We showed that gapB-encoded protein is
      expressed but at a very low level. Together, these results confirm the essential
      role for gapA in glycolysis and show that gapB is dispensable for both glycolysis
      and the pyridoxal biosynthesis pathway.

PMID- 9260968
TI  - Characterization of genes for a second Mo-dependent nitrogenase in the
      cyanobacterium Anabaena variabilis.
AB  - Anabaena variabilis ATCC 29413 is a filamentous heterocystous cyanobacterium that
      fixes nitrogen under a variety of environmental conditions. Under aerobic growth
      conditions, nitrogen fixation depends upon differentiation of heterocysts and
      expression of either a Mo-dependent nitrogenase or a V-dependent nitrogenase in
      those specialized cells. Under anaerobic conditions, a second Mo-dependent
      nitrogenase gene cluster, nifII, was expressed in vegetative cells long before
      heterocysts formed. A strain carrying a mutant gene in the nifII cluster did not
      fix nitrogen under anaerobic conditions until after heterocysts differentiated.
      The nifII cluster was similar in organization to the nifI cluster that is
      expressed in heterocysts and that includes nifBSUHDKENXW as well as three open
      reading frames that are conserved in both cyanobacterial nif clusters.

PMID- 9260970
TI  - Autogenous control of PspF, a constitutively active enhancer-binding protein of
      Escherichia coli.
AB  - Escherichia coli sigma54-dependent phage shock protein operon (pspA to -E)
      transcription is under the control of PspF, a constitutively active activator.
      Sigma70-dependent transcription of pspF is under autogenous control by wild-type
      PspF but not by a DNA-binding mutant, PspF deltaHTH. Negative autoregulation of
      PspF is continual and not affected by stimuli, like f1 pIV, that induce the pspA
      to -E operon. PspF production is independent of PspA (the negative regulator of
      the pspA to -E operon) and of PspB and -C (positive regulators).

PMID- 9260969
TI  - Cloning and characterization of two catA genes in Acinetobacter lwoffii K24.
AB  - Two novel type I catechol 1,2-dioxygenases inducible on aniline media were
      isolated from Acinetobacter lwoffii K24. Although the two purified enzymes, CD I1
      and CD I2, had similar intradiol cleavage activities, they showed different
      substrate specificities for catechol analogs, physicochemical properties, and
      amino acid sequences. Two catA genes, catA1 and catA2, encoding by CD I1 and CD
      I2, respectively, were isolated from the A. lwoffii K24 genomic library by using
      colony hybridization and PCR. Two DNA fragments containing the catA1 and catA2
      genes were located on separate regions of the chromosome. They contained open
      reading frames encoding 33.4- and 30.4-kDa proteins. The amino acid sequences of
      the two proteins matched well with previously determined sequences.
      Interestingly, further analysis of the two DNA fragments revealed the locations
      of the catB and catC genes as well. Moreover, the DNA fragment containing catA1
      had a cluster of genes in the order catB1-catC1-catA1 while the catB2-catA2-catC2
      arrangement was found in the catA2 DNA fragment. These results may provide an
      explanation of the different substrate specificities and physicochemical
      properties of CD I1 and CD I2.

PMID- 9260971
TI  - Transcription termination factor Rho is essential for Micrococcus luteus.
AB  - The growth of Micrococcus luteus, a soil microorganism that belongs to the high
      G+C gram-positive phylogenetic group, is prevented by bicyclomycin, an antibiotic
      that inhibits the activity of the M. luteus transcription termination factor Rho.
      A mutant that can grow in 0.3 mM bicyclomycin has a Rho that is insensitive to
      bicyclomycin and has the single amino acid residue change of Asp474 to Gly. These
      results indicate that the function of its Rho factor is essential for M. luteus
      and that growth of a gram-positive organism can be blocked by bicyclomycin.

PMID- 9260973
TI  - Ultraviolet light may contribute to geographic and racial blood pressure
      differences.
AB  - Mean systolic and diastolic pressures and the prevalence of hypertension vary
      throughout the world. Published data suggest a linear rise in blood pressure at
      increasing distances from the equator. Similarly, blood pressure is higher in
      winter than summer. Blood pressure also is affected by variations in skin
      pigmentation. Altered calcium, vitamin D, and parathyroid hormone status is
      associated with hypertension and may vary with latitude and season. Since changes
      in UV light affect vitamin D and parathyroid hormone status and UV light
      intensity are influenced by seasonal change and latitude, these disparate
      observations suggest an association between blood pressure and ultraviolet light.
      This discussion presents the hypothesis that reduced epidermal vitamin D3
      photosynthesis associated with high skin melanin content and/or decreased UV
      light intensity at distances from the equator, alone or when coupled with
      decreased dietary calcium and vitamin D, may be associated with reduced vitamin D
      stores and increased parathyroid hormone secretion. These changes may stimulate
      growth of vascular smooth muscle and enhance its contractility by affecting
      intracellular calcium, adrenergic responsiveness, and/or endothelial function.
      Thus, UV light intensity and efficiency of epidermal vitamin D3 photosynthesis
      may contribute to geographic and racial variability in blood pressure and the
      prevalence of hypertension.

PMID- 9260972
TI  - Cloning and mutational analysis of the gene for the stationary-phase inducible
      catalase (catC) from Pseudomonas putida.
AB  - Pseudomonas putida, a bacterium that colonizes plant roots and enhances plant
      growth, produces three isozymes of catalase (A, B, and C) in stationary-phase
      cells. A catalase probe, generated by PCR analysis of P. putida genomic DNA with
      oligomers based on typical catalase sequences, hybridized to a genomic clone that
      expressed catalase C in Escherichia coli. The catC gene from this clone had a
      2,133-bp open reading frame with a high level of identity to the stationary-phase
      specific E. coli katE. Chromosomal mutants of P. putida deficient in catalase C,
      obtained by gene interruption with a luxAB-npt cassette, demonstrated enhanced
      catC transcription in stationary-phase cells and, upon exposure to phenol, in
      logarithmic-phase cells. The catalase C-deficient cells were not impaired in
      their ability to colonize roots of bean or wheat plants grown under sterile
      conditions.

PMID- 9260974
TI  - Blunted blood pressure response to central sympathoinhibition in normotensive
      blacks: increased importance of nonsympathetic factors in blood pressure
      maintenance in blacks.
AB  - Enhanced sympathetic reactivity may predispose blacks to the development of
      hypertension and may occur because of increased sympathetic stimulation and/or
      attenuated sympathoinhibition. A potential site for such attenuated sympathetic
      inhibition may be at the level of central alpha2-adrenergic receptors, which play
      an important role in the feedback inhibition of norepinephrine release. We used
      cumulative doses (1, 2, and 3 microg/kg I.V.) of the centrally acting alpha2
      adrenergic agonist clonidine to measure the sensitivity of alpha2-adrenoceptor
      mediated sympathoinhibition and the resultant hypotensive response in 8
      normotensive blacks and 10 normotensive whites. Sympathetic activity was
      determined by radioisotope dilution methodology. Basal norepinephrine spillover
      was similar in blacks (0.80+/-0.14 microg/min) and whites (0.73+/-0.19
      microg/min, P=NS) and after clonidine decreased significantly in both blacks
      (0.21+/-0.07 microg/min, P<.0001) and whites (0.24+/-0.06 microg/min, P<.0001),
      with no difference between the groups (P=NS). Despite this similar degree of
      sympathoinhibition, the hypotensive response to clonidine was markedly blunted in
      blacks, such that mean arterial pressure decreased by only 10% in blacks but by
      21% in whites (P<.0001). The smaller blood pressure decrement after clonidine in
      normotensive blacks, in the face of an equal degree of sympathoinhibition,
      suggests that even when sympathetic tone is decreased to the same level in blacks
      and whites, normotensive blacks have less reduction in blood pressure than
      whites, implying that nonadrenergic mechanisms contribute more to blood pressure
      maintenance in blacks than whites. Whether a similar interethnic difference in
      response to sympathoinhibition occurs in hypertensive patients is as yet unknown.

PMID- 9260975
TI  - Nocturnal decline in blood pressure is attenuated by NaCl loading in salt
      sensitive patients with essential hypertension: noninvasive 24-hour ambulatory
      blood pressure monitoring.
AB  - We investigated the effect of NaCl on the circadian blood pressure rhythm in
      patients with essential hypertension classified according to the presence or
      absence of salt sensitivity. We obtained 24-hour noninvasive ambulatory blood
      pressure measurements in 64 Japanese patients with mild to moderate essential
      hypertension who ate a low NaCl diet (50 mmol/d) for 1 week, followed by a high
      NaCl diet (340 mmol/d) for 1 week. Twenty-six patients whose mean blood pressure
      was increased more than 10% by NaCl loading were classified as salt sensitive.
      The remaining 38 patients were classified as salt resistant. The nocturnal
      decline in mean blood pressure was significantly smaller in salt-sensitive
      patients (8.3+/-1.0%) than in salt-resistant patients (11.5+/-0.9%) (P<.05)
      during a high NaCl diet but was similar in both groups during a low NaCl diet.
      There was no significant difference in the prevalence of the non-dipper pattern
      between groups on a low NaCl diet, but the prevalence of the non-dipper pattern
      was significantly higher in salt-sensitive patients than in salt-resistant
      patients on a high NaCl diet (0.57 versus 0.26, chi2=6.4; P=.02; odds ratio,
      3.82). These findings suggest that the NaCl loading blunted the nocturnal decline
      in blood pressure in salt-sensitive patients but not in salt-resistant patients.

PMID- 9260976
TI  - Intrarenal determinants of sodium retention in mild heart failure: effects of
      angiotensin-converting enzyme inhibition.
AB  - The onset and the mechanisms leading to Na+ retention in incipient congestive
      heart failure (CHF) have not been systematically investigated. To investigate
      renal Na+ handling in the early or mild stages of CHF, Na+ balance and renal
      clearances were assessed in 10 asymptomatic patients with idiopathic or ischemic
      dilated cardiomyopathy and mild heart failure (HF) off treatment (left
      ventricular ejection fraction, 29.7+/-2%) and in 10 matched normal subjects
      during a diet containing 100 mmol/d of NaCl and after 8 days of high salt intake
      (250 mmol/d). Six patients were studied again after 6 weeks of treatment with
      enalapril (5 mg/d P.O.). At the end of the high salt diet, in patients with mild
      HF the cumulative Na+ balance exceeded by 110 mmol that of normal subjects
      (F=3.86, P<.001). During high salt intake, renal plasma flow and glomerular
      filtration rate were similarly increased in both normal subjects and mild HF
      patients. In spite of comparable increases of filtered Na+ in the two groups,
      fractional excretion of Na+, fractional clearance of free water, and fractional
      excretion of K+ (indexes of distal delivery of Na+) increased in normal subjects
      and were reduced in patients with mild HF. During enalapril treatment, in the
      mild HF patients the cumulative Na+ balance was restored to normal; furthermore,
      enalapril significantly attenuated the abnormalities in the distal delivery of
      Na+. Our results indicate that a defective adaptation of Na+ reabsorption in the
      proximal nephron is associated with Na+ retention in response to increased salt
      intake in the early or mild stages of HF. These abnormalities of renal Na+
      handling are largely reversed by enalapril.

PMID- 9260977
TI  - Role of natriuretic peptide receptor type C in Dahl salt-sensitive hypertensive
      rats.
AB  - The natriuretic peptide system is suggested to be involved in the pathogenesis of
      salt-sensitive hypertension; a recent report indicated that disruption of the
      atrial natriuretic peptide precursor gene caused salt-sensitive hypertension.
      However, natriuretic peptide receptor (NPR)-A knockout mice did not show enhanced
      salt sensitivity of blood pressure. The aim of the present study was to
      investigate the role of NPR-C, the other receptor for atrial natriuretic peptide,
      in increased salt sensitivity of blood pressure. Dahl salt-sensitive (DS) and
      salt-resistant (DR) rats were placed on a 0.3% or 8% NaCl diet for 4 weeks. Blood
      pressure was elevated by salt loading only in DS rats. RNase protection assay
      demonstrated that NPR-C transcript level in the kidney was reduced by chronic
      salt loading in both DR and DS rats, whereas expression of NPR-A and NPR-B was
      not altered. The reduction of NPR-C mRNA in response to salt loading was enhanced
      in DS compared with DR rats. In situ hybridization indicated that the salt
      induced NPR-C change was attributed mainly to suppressed expression of NPR-C in
      the podocytes. NPR-C gene expression was regulated by salt loading in a tissue
      specific manner; the marked decrease in NPR-C mRNA by salt loading was seen only
      in the kidney. These data suggest that the exaggerated salt-induced reduction of
      NPR-C in the kidney of DS rats may play an important role in the pathogenesis of
      salt hypertension in this animal, possibly related to impaired renal sodium
      excretion.

PMID- 9260978
TI  - Neutral endopeptidase regulates C-type natriuretic peptide metabolism but does
      not potentiate its bioactivity in vivo.
AB  - C-type natriuretic peptide (CNP) is a newly described 22-amino acid peptide of
      endothelial and renal cell origin with selective cardiovascular actions. Recent
      in vitro studies have reported that CNP is the most susceptible of all
      natriuretic peptides to enzymatic degradation by neutral endopeptidase 24.11
      (NEP). The present study was undertaken to define the role of NEP in total and
      regional CNP metabolism and the modulatory actions of NEP inhibition on the
      biological actions of CNP. CNP (10 ng x kg(-1) x min(-1)) followed by
      candoxatrilat (240 microg x kg(-1) bolus and 8 microg x kg(-1) x min(-1)), a
      potent and selective NEP inhibitor, was administered intravenously to a group of
      anesthetized mongrel dogs (group 1) to permit calculation of total metabolic
      clearance rate (MCR); results were compared with those in a group receiving
      vehicle infusion followed by candoxatrilat (group 2; both groups, n=7). NEP
      inhibition increased circulating CNP achieved by exogenous infusion and reduced
      total MCR in group 1. The regional CNP MCRs increased after CNP administration.
      While the pulmonary MCR did not change during concomitant candoxatrilat infusion,
      renal MCR was suppressed. Hemodynamic changes were not different between groups.
      A mild natriuretic and diuretic effect in association with an increase in
      circulating and urinary ANP levels was not different between groups. Urinary CNP
      excretion did not change with CNP infusion but markedly increased after NEP
      inhibition. We conclude that (1) circulating CNP achieved by exogenous CNP
      infusion is regulated by NEP in vivo, (2) regional MCRs are heterogeneous with
      NEP inhibition, (3) NEP inhibition does not potentiate acute cardiovascular
      actions of CNP, and (4) a mild natriuretic and diuretic effect observed with CNP
      and NEP inhibition may be ANP dependent.

PMID- 9260979
TI  - Characterization of a sodium-response transcriptional mechanism.
AB  - On the basis of paradigms in development wherein discrete transcriptional events
      are pivotal regulatory steps, we tested the hypothesis that transcriptional
      sodium (Na+)-response mechanisms are involved in in vivo Na+-induced responses
      relevant to normal (homeostatic) and pathophysiological (salt-sensitive
      hypertension) conditions. We used Na,K-ATPase alpha-subunit genes as molecular
      probes and the Na+ ionophore monensin to induce a dose-specific incremental
      increase in [Na+]i in rat A10 embryonic aortic smooth muscle cells. RNA blot
      analysis of rat A10 cells revealed a dose-specific (0.022 to 30 micromol/L
      monensin) upregulation of alpha1-, alpha2-, and beta1-subunit Na,K-ATPase RNA
      levels. Control beta-actin and alpha-tropomyosin RNA levels did not change. With
      the use of chloramphenicol acetyltransferase (CAT) as reporter gene, CAT assays
      of rat alpha1[-1288]CAT and human alpha2[-798]CAT promoter constructs exhibited
      induction of CAT activity in monensin (10 micromol/L)-treated A10 cells compared
      with untreated A10 cells. Promoter deletion constructs for rat alpha1[-1288]CAT
      defined a positive Na+-response regulatory region within -358 to -169 that is
      distinct from the basal transcriptional activation region of -155 to -49
      previously defined. Similarly, a positive Na+-response regulatory region is
      delimited to within -301 in the human alpha2 Na,K-ATPase 5' flanking region.
      Analysis of transgenic TgH alpha2[-798]CAT rats demonstrated sodium activation of
      human alpha2[-798]CAT transgene expression in aorta parallel to observations made
      in rat A10 aortic tissue culture cells. Southwestern blot analysis of nuclear
      extracts from monensin (10 micromol/L)-treated and control untreated A10 cells
      revealed a nuclear DNA binding protein (approximately 95 kD) that is upregulated
      by increased [Na+]i. These data provide initial characterization of a
      transcriptional Na+-response mechanism delimiting a positive Na+-response
      regulatory region in two target genes (alpha1 and alpha2 Na,K-ATPase) as well as
      detection of a Na+-response nuclear DNA binding protein. The in vitro data are
      corroborated by in vivo experimental and transgenic promoter expression studies,
      thus validating the biological relevance of the observations.

PMID- 9260980
TI  - Congenic strains for the blood pressure quantitative trait locus on rat
      chromosome 2.
AB  - A quantitative trait locus (QTL) for blood pressure was previously detected by
      linkage analysis in a region of rat chromosome 2 using segregating populations
      derived from crosses of the Dahl salt-sensitive (Dahl S) rat with rats of the
      Wistar-Kyoto (WKY) strain or Milan normotensive strain (MNS). Two congenic
      strains, S.WKY-D2N35/Nep and S.MNS-Adh/D2Mit5, have been constructed by replacing
      a region of chromosome 2 of the Dahl S rat with the homologous region (ie, low
      blood pressure QTL allele) of either the WKY or MNS rat, respectively. Systolic
      pressures of congenic strains S.WKY-D2N35/Nep and S.MNS-Adh/D2Mit5 fed a 2% NaCl
      diet for 24 days were 44+/-4.6 and 29+/-4.5 mm Hg lower, respectively, than that
      of the comparably treated Dahl S rats. The differences between congenic and Dahl
      S rats in blood pressure were highly significant (P<.001) and were corroborated
      by significantly (P<.001) lower ratio of heart weight to body weight in the
      congenic strains compared with Dahl S rats. The data from two congenic strains
      combined unequivocally establish the existence of a blood pressure QTL on rat
      chromosome 2.

PMID- 9260981
TI  - Myogenic tone attenuates pressure-induced gene expression in isolated small
      arteries.
AB  - This study was designed to determine whether pressure-induced expression of early
      response genes in the arterial wall is dependent on an increase in cell stretch
      or an increase in wall stress. Mesenteric arteries (245 to 385 microm in
      diameter) were isolated from Wistar rats and subjected to static pressures of
      either 90 mm Hg (control), 140 mm Hg, or 165 mm Hg for a period of 3 hours.
      Arteries developed a range of myogenic tone such that wall stresses in the 140
      and 165 mm Hg arteries (1.60 to 4.44x10(6) dynes/cm2) were equivalent in some
      cases to those of controls (1.76 to 2.63x10(6) dynes/cm2). Vessels subjected to
      140 or 165 mm Hg intraluminal pressure had diameters ranging from 74% to 104% of
      their relaxed diameter at 90 mm Hg, whereas control vessel diameters ranged from
      88% to 100%. At the end of each experiment, vessels were fixed in 10% formalin,
      embedded in paraffin, and sectioned for in situ hybridization. Wall stress
      significantly correlated with c-myc mRNA and 18S rRNA expression. Gene expression
      did not correlate with vessel diameter, expressed as a percentage of the relaxed
      diameter at 90 mm Hg, ie, cell stretch. The expression of beta-actin mRNA did not
      differ between vessels and showed no correlation with wall stress, suggesting
      that the induction of c-myc mRNA and 18S rRNA was part of a specific response.
      These findings show that in an isolated artery, a pressure stimulus can be
      perceived as an increase in wall stress, independently of cell stretch.
      Therefore, wall stress may be the signaling parameter in hypertension where
      arteries are tonically constricted. The inhibition of gene expression by myogenic
      constriction may explain why hypertrophy takes place in large arteries during
      hypertension but not in arterioles where increased tone reduces wall stress.

PMID- 9260982
TI  - Angiotensin II and myocyte growth: role of fibroblasts.
AB  - Angiotensin II (Ang II) has been implicated in stimulating myocyte growth in
      vitro, but the mechanism for such stimulation is still an open question. To
      understand the role of Ang II, we studied its effect on protein synthesis in rat
      neonatal and adult myocytes. Ang II (10(-8) mol/L) stimulated protein synthesis
      in neonatal myocytes by 43+/-3.5% over control. To prevent the proliferation of
      fibroblasts, bromodeoxyuridine was added, and protein synthesis in neonatal
      myocytes was reduced to 21+/-2.2% over control. In adult myocytes (cultured
      without bromodeoxyuridine), Ang II stimulated [3H]leucine incorporation by 24+/
      2.3% over control; with bromodeoxyuridine, that stimulation was reduced
      significantly (13+/-0.93% over control). These data suggest that the presence of
      fibroblasts in the cultures may control myocyte growth. When supernatant from
      pure fibroblast culture was added to myocyte preparations, a significant increase
      (49.8+/-3.5% over control) in protein synthesis occurred. Pretreatment of these
      fibroblasts with Ang II (10(-3) mol/L) further stimulated protein synthesis,
      suggesting that Ang II directly stimulates the production of a factor from
      fibroblasts. The stimulatory effect of Ang II on the release of the factor can be
      completely blocked by pretreatment with losartan, an Ang II receptor (AT1)
      blocker. Our data are the first to demonstrate a paracrine effect of a fibroblast
      derived factor that modulates myocyte growth. Fibroblast-derived factor loses its
      biological activity by (1) tryptic digestion, (2) exposure to pH below 4.0 and
      above 9.0, and (3) heating to 95 degrees C. The molecular weight of the factor is
      approximately 65 kD. The antibodies against fibroblast growth factor (both acidic
      and basic) could not inhibit this factor's stimulatory effect. Furthermore, this
      factor is heart specific and is produced at least up to the 16th passage of
      neonatal rat heart fibroblasts. Skin fibroblasts, aortic endothelial cells, and
      aortic smooth muscle cells do not produce this protein. Our data suggest that the
      observed myocyte growth by Ang II comes about via fibroblast-derived factor,
      which is increased by Ang II. Cross talk between fibroblasts and myocytes is an
      important factor in stimulating myocyte growth by Ang II.

PMID- 9260983
TI  - Angiotensin-(1-7) induces bradykinin-mediated hypotensive responses in
      anesthetized rats.
AB  - Angiotensin-(1-7) [Ang-(1-7)] reportedly potentiates hypotensive responses to
      bradykinin. We studied whether increases in circulating bradykinin would alter
      responses to Ang-(1-7). In rats anesthetized with thiobutabarbital, bradykinin
      infusion (5 microg/kg per minute I.A.) resulted in a rapid decrease in mean
      arterial pressure (MAP) of about 20 mm Hg (P<.01, n=9), although MAP slowly
      increased by 10 mm Hg after 15 minutes. When Ang-(1-7) (20, 80, and 380 nmol per
      rat I.A.) was given during bradykinin infusion, it elicited hypotension at 80 and
      380 nmol (deltaMAP: -15+/-2.7 and -21+/-3.3 mmHg, respectively; P<.001); this
      hypotension was not affected by the angiotensin type 1 antagonist L-158,809 (200
      microg/kg I.A.), the angiotensin type 2 antagonist PD 123319 (10 mg/kg I.A.),
      saralasin, or sarthran (10 microg/kg per minute). The bradykinin type 2 receptor
      antagonist icatibant (30 microg per rat) eliminated the hypotensive responses to
      Ang-(1-7), which now increased MAP at all doses tested (P<.005). Thus in the
      presence of bradykinin, Ang-(1-7) induces hypotensive responses that are blocked
      by icatibant and unaffected by angiotensin receptor antagonists. Ang-(1-7) given
      to saline-infused rats elicited hypertensive responses at all doses (deltaMAP:
      6.4+/-1.5, 12+/-1.6, and 16.3+/-2.7 mmHg, respectively; P<.01); these responses
      were abolished by L-158,809 and sarthran. In rats pretreated with saralasin, Ang
      (1-7) induced hypotension at 80 and 380 nmol (deltaMAP: -7.7+/-2.3 and -9.5+/
      2.7, respectively; P<.05), whereas icatibant abolished this response. Thus in the
      rat, Ang-(1-7) can decrease blood pressure by a mechanism involving the
      bradykinin type 2 receptor and participates with bradykinin in a vasodepressor
      pathway that may serve a counterregulatory role, modulating the vasoconstrictor
      effects of Ang II.

PMID- 9260985
TI  - Downregulation of renin gene expression by interleukin-1.
AB  - The As4.1 cell line was established from a mouse kidney tumor by transgene
      targeted tumorogenesis. These cells express high levels of renin mRNA from their
      endogenous renin gene and release approximately eightfold-more prorenin than
      active renin in culture. Levels of renin mRNA in As4.1 cells are decreased in a
      dose-dependent manner by the addition of physiological concentrations of cytokine
      interleukin-1 to the media. Stability of renin mRNA and initial rates of release
      of active renin and prorenin were not significantly altered by interleukin-1. In
      contrast, transcription initiated from a construct that consisted of 4.1
      kilobases of renin 5' flanking sequence fused to a reporter gene (chloramphenicol
      acetyltransferase) was markedly inhibited by interleukin-1. On the basis of our
      findings, we conclude that downregulation of renin synthesis caused by
      interleukin-1 occurs primarily at the level of transcription and that DNA
      sequence or sequences mediating that effect are positioned within 4.1 kilobases
      upstream of the renin gene. The physiological relevance of this regulation is
      related to the events that occur during septic shock, characterized by
      hypotension, cardiovascular collapse, multiple organ failure, and high mortality.
      Unexpectedly, hypotension associated with septic shock does not lead to
      activation of the renin-angiotensin system. The hypotension in septicemia is
      believed to be mediated by the combined action of many modulators including
      cytokines, and data presented here suggest direct involvement of interleukin-1 in
      this process.

PMID- 9260984
TI  - Angiotensin II regulates vascular smooth muscle cell pH, contraction, and growth
      via tyrosine kinase-dependent signaling pathways.
AB  - Angiotensin II (Ang II), a potent vasoactive peptide with mitogenic potential,
      influences vascular smooth muscle cell contraction and growth through receptor
      linked pathways that increase intracellular free Ca2+ concentration ([Ca2+]i) and
      pH (pHi). Activation of these second messengers by Ang II may involve tyrosine
      kinase-dependent signaling pathways. This study determined the role of tyrosine
      kinases in Ang II-stimulated pHi, and in simultaneously measured contractile and
      [Ca2+]i responses, as well as growth in cultured vascular smooth muscle cells
      from mesenteric arteries of Wistar-Kyoto rats. pHi was determined by fluorescent
      digital imaging using 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein
      acetoxymethyl ester (BCECF-AM). Vascular smooth muscle cell [Ca2+]i and
      contractile responses were assessed simultaneously by fura 2 methodology and by
      photomicroscopy in cells grown on rat tail collagen gels. Cell growth was
      determined by DNA and protein synthesis as measured by [3H]thymidine and
      [3H]leucine incorporation, respectively. The Ang II receptor subtypes (AT1 or
      AT2) through which Ang II mediates effects were assessed with [Sar1,Ile8]Ang II
      (a nonselective subtype antagonist), losartan (a selective AT1 antagonist), and
      PD 123319 (a selective AT2 antagonist). To determine whether tyrosine kinases
      influence Ang II-stimulated responses, cells were pretreated with 10(-5) mol/L
      tyrphostin A-23 (a specific tyrosine kinase inhibitor). Ang II increased pHi in a
      dose-dependent manner (pD2, 9.2+/-0.2) and significantly increased vascular
      smooth muscle cell contraction (30%) and [Ca2+]i (pD2, 7.4+/-0.1). Ang II (10(-7)
      mol/L) increased DNA ([3H]thymidine incorporation) and protein synthesis
      ([3H]leucine incorporation). [Sar1,Ile8]Ang II and losartan but not PD 123319
      abolished Ang II-elicited responses. Tyrphostin A-23 significantly attenuated Ang
      II-stimulated pHi responses; it also inhibited [Ca2+]i and contractile responses
      and cell growth. The inactive analogue tyrphostin A-1 did not alter Ang II
      stimulated actions. These results provide novel evidence for a role of tyrosine
      kinases in Ang II-mediated pHi responses in vascular smooth muscle cells and
      indicate that tyrosine kinases participate in the regulation of signal
      transduction associated with AT1 receptor subtype-mediated contraction and
      growth.

PMID- 9260986
TI  - Asp905Tyr polymorphism of protein phosphatase 1 G subunit gene in hypertension.
AB  - A possible pathogenic polymorphism in the gene for the G subunit of the glycogen
      associated regulatory form of protein phosphatase 1 (PP1 G subunit), causing an
      Asp-to-Tyr substitution at codon 905 (Asp905Tyr), has been reported to be
      associated with insulin resistance and hypersecretion of insulin in the white
      population. Since marked heterogeneity has been reported in the association of
      mutations of candidate genes with essential hypertension between Japanese and
      other ethnic groups, we investigated the association of Asp905Tyr with essential
      hypertension in Japanese subjects. The frequency of the Tyr allele in Japanese
      control subjects (0.70) was much higher than that in the Danish population (0.10,
      P<1x10(-8)), indicating that the Tyr allele, previously reported as a rare
      variant in white subjects, is a common allele in our population. The genotype
      distribution in Japanese hypertensive patients (n=109; Asp/Asp=0.09,
      Asp/Tyr=0.39, Tyr/Tyr=0.52) was not significantly different (chi2=0.7, df=2,
      P>.6) from that in normotensive control subjects (n=148; Asp/Asp=0.12,
      Asp/Tyr=0.36, Tyr/Tyr=0.52). Among subjects with different PP1 G subunit
      genotypes, there was no difference in blood pressure, serum cholesterol, plasma
      glucose and insulin levels, and glucose disposal rate estimated by the euglycemic
      hyperinsulinemic clamp test. These data indicate that the Asp905Tyr polymorphism
      of the PP1 G subunit is not associated with essential hypertension, nor with
      insulin resistance and/or hyperinsulinemia in Japanese patients with essential
      hypertension, suggesting that the polymorphism plays little if any role in
      susceptibility to insulin resistance or hypertension.

PMID- 9260987
TI  - Renal hemodynamic response to an angiotensin II antagonist, eprosartan, in
      healthy men.
AB  - In view of the vasodilator potential of angiotensin-converting enzyme (ACE)
      inhibition via prostaglandins and kinins, we asked why renin inhibition induces a
      larger renal vasodilator response than ACE inhibitors in healthy humans in
      earlier studies. One possibility was that there was a more complete blockade of
      the renin system, which could also be achieved by an angiotensin II antagonist,
      eprosartan. We measured the hormonal and renal hemodynamic responses to
      eprosartan doses, from 10 to 400 mg in 9 healthy young men in balance on a 10
      mmol/d sodium intake. The threshold eprosartan dose to influence renal perfusion
      was <10 mg, and the 100-mg dose induced a near-maximal vasodilator response of
      135+/-19.7 mL x min(-1) x 1.73 m2. When the dose was increased to 400 mg, there
      was a modest additional increase of 147+/-57 mL x min(-1) x 1.73 m(-2). A highly
      significant dose-related fall in arterial blood pressure occurred (r=-.97;
      P<.001), with no indication of a maximal response at 400 mg. In 6 additional
      subjects, we compared responses to eprosartan on a high salt and a low salt diet.
      The renal response to 200 mg eprosartan on a high salt diet, 26.0+/-6.6 mL x min(
      1) x 1.73 m(-2), was significantly less than that seen with the low salt diet
      (P<.001). There was no renal partial agonist angiotensin-like effect of
      eprosartan. Eprosartan reduced sharply the pressor, renal vascular, and hormonal
      responses to exogenous angiotensin II. The renal vasodilator response to the
      angiotensin II antagonist eprosartan closely resembles responses to renin
      inhibition and exceeds previously reported responses to ACE inhibitors. Thus,
      eprosartan probably exerted its effect via the angiotensin receptor. More
      complete blockade of the renin system can be achieved by pharmacological
      interruption at this level, a finding that could have therapeutic implications.

PMID- 9260988
TI  - Flow-mediated vasodilatation is enhanced in normal pregnancy but reduced in
      preeclampsia.
AB  - Endothelium-derived nitric oxide is proposed to play an important role in the
      lowering of peripheral vascular resistance in normal pregnancy. In women with
      preeclampsia, the function of the endothelium is compromised, and it is suggested
      that reduced nitric oxide synthesis may contribute to the elevation of blood
      pressure and activation of coagulation pathways. In this study, we have compared
      responses to increments of intraluminal flow, considered to be a physiological
      stimulus to nitric oxide release, in arteries from normotensive nonpregnant and
      pregnant women and women with preeclampsia. Small subcutaneous arteries from
      normotensive pregnant women showed substantial flow-induced relaxation, which was
      attenuated by the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine
      methyl ester (L-NAME) (mean relaxation, 48.3+/-8.0% [absence of L-NAME] versus
      19.2+/-10.6% [presence of L-NAME]), whereas those from nonpregnant women and
      women with preeclampsia demonstrated modest constriction (mean constriction,
      10.1+/-7.3% and 1.2+/-7.2%, respectively). Shear stress, the frictional force
      that is the stimulus for flow responses, was calculated from parameters of flow,
      viscosity, and artery diameter. Arteries from pregnant women showed greater
      relaxation to shear than those from nonpregnant women or those with preeclampsia.
      We conclude that flow-induced shear stress is a potent stimulus to vasodilatation
      in arteries from pregnant women and that this mechanism may lead to a fall in
      peripheral vascular resistance in normal pregnancy. Failure of this flow-induced
      dilatation may contribute to the gestational hypertension of preeclampsia.

PMID- 9260989
TI  - Aging and severity of hypertension attenuate endothelium-dependent renal vascular
      relaxation in humans.
AB  - Endothelial dysfunction may be related to cardiovascular risk factors, such as
      aging, hypertension, and atherosclerosis. We investigated whether aging and
      hypertension independently alter endothelial function in the renal circulation in
      humans in the absence of abnormalities in lipid and glucose metabolism. L
      Arginine (500 mg/kg over 30 minutes) was intravenously administered to 33
      patients with essential hypertension and 35 normotensive subjects. The L-arginine
      induced increases in renal plasma flow (10.1+/-0.8% versus 15.8+/-0.9%, P<.05)
      and plasma cGMP (53+/-4% versus 82+/-5%, P<.05) were significantly smaller in
      patients with essential hypertension than in the normotensive subjects.
      Multivariate stepwise regression analysis showed that age (P<.0002) and the mean
      blood pressure (P<.0001) were independently and negatively correlated with the
      renal plasma flow response to L-arginine. Age (P<.002), mean blood pressure
      (P<.0001), and male sex (P<.05) were independently correlated with the L-arginine
      induced increase in plasma cGMP. The peak change in plasma cGMP was significantly
      correlated with the L-arginine-induced increase in renal plasma flow (r=.63,
      P<.001). These findings suggest that aging and hypertension may independently
      impair endothelium-dependent renovascular dilation and that this effect may be
      caused at least in part by a decrease in nitric oxide production.

PMID- 9260990
TI  - Effect of bilateral nephrectomy on active renin, angiotensinogen, and renin
      glycoforms in plasma and myocardium.
AB  - In an attempt to clarify the relationship of the circulating and myocardial renin
      angiotensin systems, active renin concentration, its constituent major glycoforms
      (active renin glycoforms I through V), and angiotensinogen were measured in
      plasma and left ventricular homogenates from sodium-depleted rats under control
      conditions or 2 minutes, 3 hours, 6 hours, and 48 hours after bilateral
      nephrectomy (BNX). Control myocardial renin concentration was 1.4+/-0.1 ng
      angiotensin I (Ang I) per gram myocardium per hour and plasma renin concentration
      was 6.7+/-1.1 ng Ang I per milliliter plasma per hour. Control myocardial
      angiotensinogen was 0.042+/-0.004 micromol/kg myocardium and plasma
      angiotensinogen was 1.5 micromol/L plasma. Two minutes after BNX and
      corresponding stimulation of renin secretion by anesthesia and surgery, plasma
      renin concentration was increased disproportionately compared with myocardial
      renin. Three, 6, and 48 hours after BNX, renin decay occurred significantly
      faster from the plasma than from the myocardium. Forty-eight hours after BNX,
      myocardial renin concentrations had fallen to 15% of control values, while
      myocardial angiotensinogen concentrations had increased 12-fold and plasma
      angiotensinogen concentrations had increased by only 3.5-fold. Myocardial renin
      glycoform proportions were identical in myocardial homogenates and plasma in
      control animals. At 6 hours BNX, the proportions of plasma active renin
      glycoforms I+II fell, while those in the myocardium significantly increased. We
      conclude that in control rats, active renin and active renin glycoforms are
      distributed as if in diffusion equilibrium between plasma and the myocardial
      interstitial space. After BNX, myocardial renin concentration falls dramatically,
      suggesting that most cardiac renin is derived from plasma renin of renal origin.
      After BNX, renin glycoforms I+II are preferentially cleared from the plasma but
      preferentially retained by the myocardium. Control myocardial angiotensinogen
      concentrations are too low to result from simple diffusion equilibrium between
      plasma and the myocardial interstitium.

PMID- 9260991
TI  - Birth weight, growth, and blood pressure: an annual follow-up study of children
      aged 5 through 21 years.
AB  - Associations between birth weight and blood pressure have been found in children
      and adults. In this longitudinal study, the objective was to assess the relation
      between birth weight and blood pressure level and the change in blood pressure
      from childhood and young adolescence into adulthood. A cohort of 483 children
      from a middle-class community in the town of Zoetermeer in the Netherlands had
      annual measurements of blood pressure during an average follow-up period of 14
      years. For 330 of these participants, initially aged 5 through 21 years, birth
      weight data were collected, which were related to blood pressure level and blood
      pressure change. An inverse association between birth weight and systolic blood
      pressure was found, with adjustment for current body height and weight, sex, and
      use of alcohol, cigarettes, and oral contraceptives. This inverse association was
      found for the total follow-up in 5- to 37- year-olds (regression coefficient: 
      2.4 mm Hg/kg; 95% confidence interval: -3.9 to -1.0, as well as in most
      individual age groups: 5 through 9 years (-0.6 mm Hg/kg, -3.2 to 2.0); 10 through
      14 years (-2.5 mm Hg/kg, -4.7 to -0.4); 15 through 19 years (-3.1 mm Hg/kg, -4.9
      to -1.2); 20 through 24 years (-2.7 mm Hg/kg, -4.6 to -0.9); 25 through 29 years
      (-2.0 mm Hg/kg, -3.9 to -0.01); and 30 through 37 years (-1.9 mm Hg/kg, -4.6 to
      0.7). For diastolic blood pressure, there appeared to be an inverse association
      with birth weight in the age group of 30 through 37 years, both unadjusted (-2.0
      mm Hg/kg, -4.6 to 0.5) and adjusted for risk factors other than sex (-2.3 mm
      Hg/kg, -4.7 to 0.1), although these findings were of borderline statistical
      significance. The results were independent of gestational age and were similar in
      the group of subjects with low birth weight but normal gestational age (-2.7 mm
      Hg/kg, -4.3 to -1.0). In relation to systolic blood pressure, birth weight showed
      a significant interaction with body mass index (regression coefficient, 0.02;
      SE=0.01; P=.05). There was no relation between birth weight and change in
      systolic or diastolic blood pressure with age. Our longitudinal study shows that
      birth weight is consistently inversely associated with systolic blood pressure
      level from childhood to young adulthood and with diastolic blood pressure in
      young adulthood. Birth weight is not related to change of blood pressure with
      increasing age. Low birth weight in combination with high current body mass index
      seems to be of particular importance in the development of high blood pressure.

PMID- 9260992
TI  - Early induction of angiotensin I-converting enzyme in rat carotid artery after
      balloon injury.
AB  - Several studies have demonstrated the effectiveness of angiotensin I-converting
      enzyme (ACE) inhibitors in preventing the neointima formation found after
      denudation of the rat carotid artery by balloon injury. The aim of the present
      study was to determine the role of ACE in this model and to compare the treatment
      with the ACE inhibitor ramiprilat with that with the angiotensin II antagonist HR
      720. The endothelial layer of the left carotid artery was removed using an
      inflated balloon catheter. Injured and control vessels were both submitted to
      histomorphological analysis and DNA content quantification at 2, 4, 6, 8, 12, and
      14 days after injury. Evaluation of neointima thickening demonstrated a slow but
      steady increase of neointima that was significant after day 6 and reached 30% of
      the lumen in 2 weeks. This was paralleled by an increase in DNA content, which
      was significant 4 days after injury. ACE mRNA levels were quantified by
      polymerase chain reaction after reverse transcription. Measurement of ACE mRNA
      levels revealed a significant upregulation 2 and 8 days after injury, with no
      significant difference when compared with control tissue at later time points.
      ACE activity was also significantly enhanced at 2 and 8 days after injury, with
      no significant difference when compared with control tissue at later time points.
      In addition, the treatment with ramiprilat was more efficient in reducing
      neointima formation than that with HR 720. These data underlie the role of ACE in
      this model of restenosis. The early induction of ACE expression after endothelial
      injury but before significant changes in the vessel structure suggests that ACE
      activity might be one of the mechanisms that trigger neointima formation in the
      rat.

PMID- 9260993
TI  - Effects of renin-angiotensin blockade on sympathetic reactivity and beta
      adrenergic pathway in the spontaneously hypertensive rat.
AB  - As interactions between the renin-angiotensin and sympathetic nervous systems
      have been suggested in the pathogenesis of hypertension, we wanted to investigate
      the effect of chronic renin-angiotensin blockade with losartan and enalaprilat on
      the sympathetic reactivity to hypotension and on the cardiac beta-adrenergic
      coupled adenylyl cyclase pathway in 12-week-old Wistar-Kyoto rats (WKY) and
      spontaneously hypertensive rats (SHR). Both treatments, exerting equipotent
      shifts of angiotensin-pressure responses, lowered blood pressure and attenuated
      cardiac hypertrophy similarly in SHR. The nitroprusside-induced hypotension was
      similar in both strains, but the associated increases in plasma catecholamines
      and heart rate were higher in SHR. In SHR treated with losartan and enalaprilat,
      the nitroprusside-induced hypotension was greater and associated with markedly
      attenuated increases in norepinephrine and heart rate. The binding affinity of
      cardiac beta-adrenoceptors was significantly lower, and beta2-adrenoceptor
      subtype was dominant in untreated SHR in contrast to WKY, in which beta1
      adrenoceptor subtype was dominant. Enalaprilat treatment increased total beta
      adrenoceptor density, whereas both treatments restored the binding affinity and
      beta1- and beta2-adrenoceptor proportions to normal in SHR. Isoproterenol-,
      guanylylimidodiphosphate [Gpp(NH)p]-, and forskolin-stimulated adenylyl cyclase
      reactivity was increased in SHR. Enalaprilat restored adenylyl cyclase reactivity
      to normal in SHR and reduced the sensitivity (EC50) of Gpp(NH)p-induced cAMP
      formation in both strains. The present study supports the possibility that
      functional alterations of the renin-angiotensin and sympathetic systems are
      involved in hypertension in SHR. The antihypertensive action of losartan and
      enalaprilat in SHR may be partly mediated through the normalization of
      sympathetic hyperreactivity and the restoration of beta-adrenergic signaling
      pathway sensitivity.

PMID- 9260994
TI  - Role of cardiac output in ethanol-evoked attenuation of centrally mediated
      hypotension in conscious rats.
AB  - Our previous studies have shown that ethanol selectively counteracts centrally
      mediated hypotensive responses. This study investigated the role of cardiac
      output and peripheral resistance in the antagonistic interaction between ethanol
      and antihypertensive drugs. Changes in blood pressure, heart rate, cardiac index,
      stroke volume, and peripheral resistance elicited by clonidine and subsequent
      ethanol or saline administration were evaluated in conscious rats. The aortic
      barodenervated rat was employed because it exhibits greater hypotensive responses
      to clonidine compared with the intact rat. Aortic barodenervation elicited acute
      rises in blood pressure, heart rate, and peripheral resistance, whereas cardiac
      index and stroke volume were not altered. The blood pressure of conscious aortic
      barodenervated rats returned to sham-operated levels by 48 hours due to
      concomitant reductions in cardiac index and stroke volume; the peripheral
      resistance, however, remained significantly elevated. Clonidine (30 microg/kg,
      I.V.) elicited greater decreases in blood pressure in aortic barodenervated
      compared with sham-operated rats. The hypotension was caused by decreases in
      cardiac index and stroke volume because peripheral resistance did not change.
      Ethanol (1 g/kg, I.V.) counteracted the hypotensive effect of clonidine and
      raised blood pressure to levels higher than preclonidine values. Significant
      (P<.05) increases in cardiac index and stroke volume and decreases in peripheral
      resistance accompanied the pressor effect of ethanol. Additional control groups
      were included in the study to determine the selectivity of the interaction. A
      dose of hydralazine (0.5 mg/kg, I.V.) was used that produced similar hypotension
      to that evoked by clonidine in aortic barodenervated rats. Hydralazine-evoked
      hypotension was similar in denervated and control rats and resulted from
      significant reductions in peripheral resistance. Reflex increases in heart rate
      and stroke volume and hence cardiac output were observed. Ethanol given after
      hydralazine produced a short-lived pressor effect (<5 minutes versus 40 minutes
      in the case of clonidine) and counteracted the sympathetically mediated increases
      in cardiac output, stroke volume, and heart rate. These findings support our
      hypothesis that ethanol selectively counteracts hypotensive responses of central
      origin by reversing the reduction in cardiac output elicited by clonidine.

PMID- 9260995
TI  - Stimulation of imidazoline receptors inhibits proliferation of human coronary
      artery vascular smooth muscle cells.
AB  - Vascular smooth muscle cells of rat aorta express imidazoline receptors whose
      stimulation, by drugs or an endogenous ligand, agmatine, inhibits serum
      stimulated proliferation. We investigated whether imidazoline receptors are
      expressed in human vascular smooth muscle cells if their stimulation is
      antiproliferative. Cultured human coronary artery vascular smooth muscle cells
      express a nonadrenergic binding site for 3H-idazoxan and an imidazoline receptor
      binding protein as revealed by immunocytochemical and immunoblot analyses with a
      specific antibody. Idazoxan and agmatine dose-dependently inhibited serum
      stimulated proliferation of these cells as measured by the incorporation of 3H
      thymidine (IC50: 5 and 70 micromol/L, respectively) and serum-stimulated
      expression of proliferating cell nuclear antigen and cell numbers. The agents
      inhibited proliferation of human and rat (aorta) smooth muscle cells stimulated
      by either norepinephrine (6560+/-440 disintegrations per minute norepinephrine
      versus 3345+/-220 norepinephrine and idazoxan), angiotensin II (7680+/-335
      disintegrations per minute angiotensin II versus 3769+/-450 angiotensin II and
      idazoxan), or platelet-derived growth factor (IC50: 3 micromol/L for idazoxan and
      40 micromol/L for agmatine), indicating inhibition of mitosis mediated by G
      protein or receptor tyrosine kinase pathways. We conclude that human vascular
      smooth muscle cells express imidazoline-receptors whose activation inhibits
      proliferation by interacting at a distal step in an intracellular signal cascade
      common to G-protein and receptor tyrosine kinase mitogenic pathways. Agmatine,
      synthesized in endothelium, may act as a paracrine regulator of vascular smooth
      muscle cell proliferation through imidazoline receptors, and agents acting at
      this site may be useful in treating vascular hyperplasia.

PMID- 9260996
TI  - Initial characterization of hamsters with spontaneous hypertension.
AB  - The purpose of this study was to begin to characterize a new inbred strain of
      adult male hamsters with established spontaneous hypertension along with their
      genetically/age-matched normotensive controls. We found that mean arterial
      pressure was 162+/-3 mm Hg in hypertensive hamsters and 94+/-4 mm Hg in controls
      (mean+/-SEM; P<.05). Body weight was significantly lower in hypertensive hamsters
      relative to normotensive hamsters (P<.05). Hypertension was associated with a
      significant increase in heart weight, thickness of the left ventricular wall, and
      amplitude of the QRS complex in standard electrocardiographic leads I and aVR
      (P<.05). No gross or microscopic abnormalities were observed in other organs.
      Plasma renin activity and the number of circulating neutrophils were
      significantly increased in hypertensive hamsters relative to controls (P<.05).
      Serum concentrations of creatinine, blood urea nitrogen, sodium, potassium, and
      calcium as well as urinalysis were similar in both groups. Overall, these data
      suggest that the spontaneously hypertensive hamster could be a suitable model for
      the study of spontaneous hypertension.

PMID- 9260997
TI  - Natriuretic peptides as markers of ventricular dysfunction.

PMID- 9260998
TI  - Vascular gap junctional communication and heptanol.

PMID- 9261000
TI  - Experience with segmental reconstruction of the radiated mandible with
      alloplastic prostheses.
AB  - Reconstruction of the mandible after radiation therapy and segmental resection is
      often complicated by wound breakdown, osteoradionecrosis, and crippling of the
      oral cavity. These complications make patient salvage after radiated oral
      carcinoma a high-risk endeavor. Although head and neck surgeons have improved the
      reliability of mandibular reconstruction with microvascular free tissue transfer,
      medical and oncologic issues may prohibit their application. This report presents
      12 selected cases undergoing alloplastic reconstruction of the mandible and soft
      tissue reconstruction of the oral cavity. Although not as reliable as some
      reports of free tissue transfers, the results were reproducible and satisfactory
      in these cases, with time-efficient hospitalization and functional
      rehabilitation. Ten of 12 prosthetic reconstructions have been durable in this
      study population for as long as 36 months.

PMID- 9260999
TI  - Hypopharyngeal cancer patient care evaluation.
AB  - A survey was conducted to identify demographics and standards of care for
      treatment of hypopharyngeal squamous cell carcinoma in the United States. Data
      were accrued from voluntary submission of cancer registry and medical chart
      information from 769 hospitals representing 2939 cases diagnosed from 1980 to
      1985 and 1990 to 1992. Clinical findings, diagnostic procedures employed,
      treatment practices, and outcome are presented. Overall, 5-year disease-specific
      survival was 33.4%, which segregated to 63.1% (stage I), 57.5% (stage II), 41.8%
      (stage III), and 22% (stage IV). Survival was best for patients treated with
      surgery only (50.4%), similar with combined surgery and irradiation (48%), and
      worse with irradiation only (25.8%). This analysis provides a standard to which
      current treatment practice and future clinical trials may be compared.

PMID- 9261001
TI  - Subtotal parotidectomy: a 10-year review (1985 to 1994).
AB  - A subtotal parotidectomy is a conservative resection in which less than a
      superficial lobectomy is performed and less than a full facial nerve is
      dissected. From 1985 to 1994, 146 subtotal parotidectomies were performed for a
      variety of benign and limited, low-grade malignant tumors. The procedure is based
      on the premises that adequate margins are necessary, that the procedure can be
      terminated when these margins are obtained, and that the true margin is usually
      the tumor-to-nerve margin. For selective neoplasms the subtotal parotidectomy has
      many advantages with results that equal or surpass the classic superficial
      lobectomy.

PMID- 9261002
TI  - Resource utilization and patient morbidity in head and neck reconstruction.
AB  - Many papers have addressed the technical aspects of free tissue transfer in head
      and neck cancer patients. However, there has not been a critical assessment of
      the impact of free tissue transfer on resource utilization and patient morbidity
      compared with pedicle flap reconstructions. Two cohorts of patients derived from
      245 consecutive reconstructions were tightly matched by age, site, stage, and
      histology, yielding 44 patient pairs differing in method of reconstruction.
      Patients undergoing free flap reconstruction spent more time in the operating
      room than those reconstructed with pedicled flaps (993 min vs. 777 min, P <
      0.0001). The group with free flap reconstruction spent fewer days in the surgical
      intensive care unit and hospital (2 days vs. 2.5 days; 18.5 days vs. 22.6 days).
      This difference is attributed to the paucity of postoperative complications in
      the group with free flap reconstruction (fistula formation 4.5% vs. 21%, P <
      0.04). These data indicate that the continued use of sophisticated reconstructive
      techniques in head and neck cancer patients is economically sound as assessed by
      patient morbidity and resource utilization.

PMID- 9261003
TI  - Cochlear implantation in common cavity malformations using a transmastoid
      labyrinthotomy approach.
AB  - The transmastoid facial recess approach has become the standard technique for
      cochlear implantation. Although this approach has been used for implantation in
      patients with common cavity deformities, it is not without increased risk to the
      facial nerve. Using a direct approach to the common cavity that circumvents the
      facial recess, we have successfully implanted four patients with common cavity
      deformities. An aberrant facial nerve in one patient would have precluded
      placement of the electrode array using standard cochlear implant techniques. As
      demonstrated in these four patients, the direct approach to the common cavity is
      an effective approach for placement of the electrode array, minimizes risk to the
      facial nerve, and may decrease the likelihood of postoperative cerebrospinal
      fluid leaks. Intraoperative video footage demonstrates the feasibility and
      facility of this approach in patients with common cavity deformities.

PMID- 9261004
TI  - Implantation of the lateral cochlear wall for auditory nerve stimulation.
AB  - Although cochlear implants now regularly achieve gratifying results, traditional
      intrascalar implants have certain limitations. Extraluminal implants may offset
      some of these problems by accessing neurons subserving a wider tonotopic range,
      avoiding intracochlear insertion trauma, and offering alternatives when cochlear
      obliteration is present. We have investigated the utility of a lateral cochlear
      wall implant in a normal-hearing cat model with implants at the middle and basal
      turns, and found successful activation of the auditory nerve at thresholds of
      28.1 and 40.6 microA, respectively. No adventitial stimulation of the facial
      nerve was noted within the dynamic range. Maximum responsiveness was observed
      with implants of the middle turn of the cochlea, an area that is not reliably
      approached with current intrascalar implants. These observations support and
      extend prior observations of the feasibility of extraluminal stimulation of the
      auditory nerve.

PMID- 9261005
TI  - Individualizing hearing preservation in acoustic neuroma surgery.
AB  - Surgical series of hearing preservation in acoustic neuroma usually emphasize a
      team's results with one particular technique. This report reviews acoustic
      neuroma outcomes of individualizing the surgical approach to patient and tumor
      characteristics. This study reviews 60 consecutive hearing preservation acoustic
      neuroma surgeries in a total series of 330 acoustic neuromas. Tumor sizes ranged
      from 0.3 to 4 cm in patients ranging from 23 to 74 years of age. Middle fossa
      surgery was performed in 57%, retrosigmoid in 43%. Overall, measurable hearing
      was preserved in 77%, and useful hearing in 67%. Among middle fossa cases, 85%
      had measurable and 74% had useful hearing. Among retrosigmoid surgeries, 65% had
      measurable hearing and 58% had useful hearing. Overall, long-term facial nerve
      function was excellent (grade I or II) in 90% and poor (grade V or VI) in 2%.
      There was one case of bacterial meningitis (2%), and cerebrospinal fluid leaks
      requiring surgery occurred in four patients (7%). The hearing preservation and
      other outcome parameters in this series compare favorably with other reports. We
      believe that individualizing the surgical approach to the patient's tumor
      characteristics and clinical features contributed to the high rate of hearing
      preservation.

PMID- 9261006
TI  - Medial antebrachial cutaneous nerve: a new donor graft for repair of facial nerve
      defects at the skull base.
AB  - When grafting a facial nerve defect after resection of a skull base cancer, the
      use of the greater auricular nerve is generally contraindicated because of
      concern of malignant involvement. In the past, the sural nerve was used as a
      donor graft for reconstruction of the facial nerve. We have found a sensory
      branch of the median nerve of the upper arm, the medial antebrachial cutaneous
      (MAC) nerve, to be a suitable option for facial nerve grafting. The MAC nerve
      provides a good diameter match for the facial nerve and has branching to allow
      reconstruction of the distal facial nerve in the parotid bed. The length is
      adequate to graft from the brainstem to the distal facial branches. Loss of
      sensation is limited and well tolerated by the patient. The MAC nerve has been
      used in grafting in 15 patients with skull base disease and facial nerve defects.
      No complications have been encountered, and the functional return appears to be
      similar to other grafts. In our practice the MAC nerve is a valuable option for
      facial nerve repair at the skull base.

PMID- 9261007
TI  - Sensorineural hearing loss in the mdx mouse: a model of Duchenne muscular
      dystrophy.
AB  - Sensorineural hearing loss has been identified in several types of muscular
      dystrophy, but few studies have investigated any relationship between Duchenne
      muscular dystrophy and hearing. An animal model of Duchenne muscular dystrophy,
      the mdx mouse, exhibits the same genetic defect as humans. We performed brainstem
      auditory evoked responses on mdx and control mice in order to assess
      sensorineural hearing loss. The amplitude and latency of wave I for each animal
      were measured at increasing sound pressure levels. A significant increase in
      threshold and a decrease in wave I amplitude were found in the mdx mice. These
      results indicate that significant sensorineural hearing loss is associated with
      muscular dystrophy in the mdx mouse. Possible cellular mechanisms contributing to
      the hearing deficit are presented.

PMID- 9261008
TI  - Anatomic location of the tongue base neurovascular bundle.
AB  - Knowledge of the location of the hypoglossal/lingual artery neurovascular bundle
      (HLNVB) is essential in performing tongue base resections for neoplasm and for
      obstructive sleep apnea. Transoral and transcervical resections of the tongue
      base may be performed with greater exposure and certainty when the relationship
      of the HLNVB to local landmarks is understood; knowledge of the HLNVB allows
      resection of a larger amount of contralateral tongue base during partial
      glossectomy without violating the contralateral remnant tongue's blood supply.
      Ten cadaver heads were dissected to determine the position of the HLNVB with
      respect to soft tissue and bony landmarks at the tongue base. Our results
      indicate the position of the tongue base HLNVB is significantly inferior and
      lateral, that is, 2.7 cm inferior and 1.6 cm lateral to the foramen cecum, 0.9 cm
      superior to the hyoid bone, and 2.2 cm medial to the mandible. This inferolateral
      location allows the potential for aggressive tongue base resection without
      neurovascular compromise.

PMID- 9261009
TI  - Safety of direct laryngoscopy as an outpatient procedure.
AB  - The safety of outpatient direct laryngoscopy has recently been challenged in the
      literature. We reviewed the first 589 direct laryngoscopies performed at a new
      outpatient surgery center. There were nine unplanned admissions to the hospital,
      including five airway emergencies that developed within the first 30 min after
      extubation. Three patients required reintubation before leaving the operating
      room. On postoperative telephone follow-up, 9% complained of mild to moderate
      sore throat. There were no major complications after discharge. We conclude that
      the risk of airway emergencies after direct laryngoscopy is less than 1% in
      carefully selected patients. The procedure can be safely performed as an
      outpatient procedure as long as transportation to a hospital is readily available
      for the few patients in whom complications arise.

PMID- 9261010
TI  - Sodium ipodate (oragrafin) in the preoperative preparation of Graves'
      hyperthyroidism.
AB  - Fourteen Graves' hyperthyroid patients who had been prepared for surgery with
      sodium ipodate (SI) 500 mg orally twice daily for 3 days were retrospectively
      studied. SI was administered in combination with propylthiouracil (10 cases) and
      beta blockers (all cases), which had been previously initiated. Free serum
      thyroxine (T4) and total triiodothyronine (T3) concentrations were measured
      before and after SI therapy on the morning of surgery. SI treatment significantly
      reduced total T3 concentration from 445.9 to 193.4 ng/dL (P < 0.0001) and free T4
      concentration from 3.874 to 2.800 ng/dL (P = 0.0003). Preoperatively, only one
      patient had persistent tachycardia, and intraoperatively this same patient
      required beta blockers. Blood loss was unremarkable or reduced (average blood
      loss, 121 mL). On clinical examination glands were firm with normal or somewhat
      decreased vascularity. On histologic study all glands demonstrated changes
      consistent with treated Graves' disease. Preoperative treatment with SI appears
      to be a safe and efficacious method of preparing hyperthyroid patients for
      surgery.

PMID- 9261011
TI  - Necrotizing fasciitis of the face.
AB  - Necrotizing fasciitis (NF) is a rapidly progressive soft tissue infection with
      high morbidity and mortality rates. Its occurrence in the head and neck region is
      uncommon, the majority of reported cases being limited to involvement of the
      neck, usually from infections of dental or pharyngeal origin. Involvement of the
      face from NF is rare; only 35 such cases have been reported in the literature
      since 1960. It is not only associated with a high mortality but can also result
      in severe disfigurement of the face, posing challenging reconstructive problems.
      Successful management of facial NF requires early diagnosis, prompt institution
      of broad spectrum antibiotics, aggressive surgical debridement to control the
      infection, and reconstruction of the resultant soft tissue defects. This report
      describes four additional cases of facial necrotizing fasciitis. One of the four
      patients died as a result of sepsis and multi-organ system failure. Two of the
      three surviving patients had significant facial disfigurement. A comprehensive
      review of the facial NF cases reported in the literature is also provided. Based
      on our experience with facial NF and the results of all previous case reports,
      the clinical manifestations, pathogenesis, and management of this disease are
      discussed.

PMID- 9261012
TI  - Endoscopic sinus surgery complications in residency.
AB  - Otolaryngology has seen a rapid proliferation of functional endoscopic sinus
      surgery, and there is variability in the teaching of the procedure, in part
      because of the seriousness of the complications. A retrospective review of 106
      consecutive cases was conducted at a teaching program to evaluate complications.
      Complication rates were combined and compared with the reported complication
      rates of other teaching programs and practicing otolaryngologists. The
      complication rate in our program was 13.9%; all were minor complications. This
      compared favorably with the rates of other programs (6% to 29%). The combined
      complication rate for residency training programs (16.6%) was significantly
      greater than the nonresident complication rate (10.5%). When divided into major
      and minor complications, the resident minor complication rate (15.9%) was
      significantly greater than the nonresident rate (8%), yet the major complication
      rates were significantly less for the resident group (0.7%) than for the
      nonresident group (2.5%). In addition, complications were significantly greater
      when procedures were performed under general anesthesia as compared with local
      anesthesia, and estimated blood loss was significantly greater under general
      anesthesia.

PMID- 9261013
TI  - Nasal reconstruction using a combination of alloplastic materials and autogenous
      tissues: a surgical alternative.
AB  - Re-creation of a functional and aesthetically acceptable nose after partial nasal
      defect requires accurate reproduction of nasal lining, support, and coverage.
      Most authors recommend an approach to reconstruction with cantilevered bone
      grafting and paramedian forehead flap placement. The authors propose an
      alternative approach for selected patients with total or near-total nasal defects
      combining both alloplastic and autogenous tissues. This method uses vitallium or
      titanium mesh for the dorsal framework formation, tissue-expanded paramedian
      forehead flap for soft tissue coverage, and composite chondrocutaneous auricular
      grafts for tip reconstruction. Nine individuals underwent nasal reconstruction
      using this method. The indications, details, and potential advantages of this
      technique are described with accompanying photographic results. A flexible
      approach using a combination of alloplastic materials and autogenous tissues
      provides additional reconstructive options for individuals with total or near
      total nasal defects.

PMID- 9261014
TI  - Hearing results with cartilage tympanoplasty.
AB  - Cartilage has shown promise as a graft material to close perforations in the
      tympanic membrane (TM), particularly in cases of advanced middle ear pathology.
      Although it is similar to fascia, its more rigid quality tends to resist
      resorption and retraction. However, it is this rigid quality that has led many to
      anticipate a significant conductive hearing loss when using cartilage to
      reconstruct the TM. Because little has been reported in the literature comparing
      hearing results using cartilage with results using other grafting materials, this
      retrospective study was conducted to compare the hearing results of patients with
      cartilage tympanoplasty with results in patients who underwent revision
      tympanoplasty using perichondrium. Both series of patients had undergone type I
      tympanoplasty, and the middle ear pathology was considered to be similar between
      the two groups. TM closure was achieved in all 22 patients undergoing cartilage
      reconstruction, but three of the 20 patients undergoing perichondrium
      reconstruction had a recurrent perforation during the follow-up period
      (approximately 1 year). The average pre- and postoperative pure-tone average air
      bone gap (PTA-ABG) was 21.1 dB and 6.8 dB for the cartilage group and 17.9 dB and
      7.7 dB for the perichondrium group, respectively. These gains in hearing were
      statistically significant (P < 0.001 in each case), but there was no
      statistically significant difference in hearing results between the two groups.
      Analysis of the PTA-ABG as a function of percentage of TM reconstructed showed no
      statistically significant difference in hearing results due to percentage of
      cartilage used. These results indicate that cartilage tympanoplasty offers the
      possibility of a rigorous TM reconstruction with excellent postoperative hearing
      results.

PMID- 9261015
TI  - Preoperative temporal bone computed tomography scan and its use in evaluating the
      pediatric cochlear implant candidate.
AB  - Preoperative computed tomography (CT) scan evaluation of the temporal bones in
      cochlear implant candidates plays a crucial role in determining candidacy and the
      side of implantation. The CT scans allow the surgeon to carefully review the
      anatomy of the inner ear and mastoid cavity in order to predict any potential
      difficulties or complications that may be encountered during the implant
      insertion. We retrospectively reviewed 50 preoperative CT scans of the temporal
      bone in children who have been successfully implanted. In these scans, we
      assessed the degree of mastoid pneumatization, cochlear anatomy and patency, size
      of the vestibular aqueduct, cochlear aqueduct, and internal auditory canal. We
      analyzed our findings and measurements and compared our results with the degree
      of difficulty noted in the insertion of the implant, the number of electrodes
      inserted in each case, and the overall complication rate. From this radiographic
      review, we have created a checklist for cochlear implant surgeons in order to
      highlight key features that need to be recognized in the temporal bone scan in
      preoperative evaluation of cochlear implant candidates.

PMID- 9261016
TI  - Argon laser irradiation to the semicircular canal.
AB  - In order to elucidate the effects of argon laser irradiation on the lateral
      semicircular canal of the guinea pig, the vestibular labyrinth was histologically
      studied after irradiation, using the conventional celloidin method. Irrigation of
      the external meatus with ice water was used to evaluate the function of the
      semicircular canal by recording caloric nystagmus. When irradiation was
      performed, a laser probe was approximated to the lateral canal, 0.5 to 1 mm away
      from the surface of the canal. Each time, power applied was 1.0 W on the dial of
      the laser machine. The duration of irradiation was 0.5 s. The lateral canal was
      irradiated one to 15 times. Twenty-five to 87 days after irradiation, the
      temporal bones were fixed in Heidenhein-Susa solution, removed, and subjected to
      celloidin processing. The irradiated bony wall of the lateral canal demonstrated
      charring. Lucent areas were observed around and under the charred area. The
      semicircular duct showed shrinkage with disappearance of the trabecular mesh. New
      bone formation was observed along the endosteum of the irradiated area. The
      lateral canal was completely occluded by ossification with or without fibrosis
      when sufficient energy was applied. The anterior and posterior canals were
      normal. Caloric tests using 5 mL of ice water for 5 s failed to elicit nystagmus
      on the irradiated side.

PMID- 9261017
TI  - Calcium channel blockade reduces noise-induced vascular permeability in cochlear
      stria vascularis.
AB  - Exposure to noise results in multiple perturbations of cochlear microcirculation,
      including increases in vascular permeability. There is evidence that these events
      are mediated, in part, by calcium channels. The current study examined the
      effects of calcium channel blockade on the diameter and permeability of cochlear
      vessels during noise exposure. Subjects were exposed to either noise alone or
      noise after verapamil pretreatment. Vessels of the cochlear stria vascularis were
      imaged using intravital microscopy. Animals exposed to noise showed decreases in
      diameter and increased permeability above baseline levels. Animals pretreated
      with the calcium channel blocker verapamil and exposed to noise demonstrated
      increases in vessel diameter and no changes in permeability. These data indicate
      that calcium channel blockade reduces noise-induced microvascular permeability.
      Treatment strategies designed to protect from increases in vascular permeability
      due to noise exposure may reduce temporary threshold shifts.

PMID- 9261018
TI  - Gas exchange function through the mastoid mucosa in ears after surgery.
AB  - Gas exchange function through the mastoid mucosa was investigated in ears after
      surgery using nitrous oxide. Increase in the mastoid pressure was assessed by a
      micropressure sensor placed in the mastoid cavity during the second-stage
      revision operation performed under general anesthesia using 67% nitrous oxide,
      33% oxygen, and sevoflurane on 14 ears with chronic adhesive otitis media or
      cholesteatoma as well as on seven ears without inflammation as controls. All
      seven control ears showed pressure increase in the mastoid in various degrees. In
      the 14 postoperative ears, nine of the 10 ears on which the mastoid mucosa had
      previously been able to be preserved in various degrees showed pressure increase
      in the mastoid, but none of the remaining four ears, which had previously had
      mastoidectomy, showed any pressure increase. The presence or absence of the
      mastoid pressure increase of those ears was also found to be correlated well with
      the presence or absence of mastoid aeration on computed tomography examined just
      before the second-stage operation. These results appear to indicate that, in ears
      after surgery, recovery of both the gas exchange function and aeration in the
      mastoid is expected only when the mastoid mucosa can be preserved even partially.

PMID- 9261019
TI  - Hearing preservation after acoustic neuroma resection with tumor size used as a
      clinical prognosticator.
AB  - Three hundred sixty-four patients referred to the Chicago Otology Group for
      acoustic tumor removal between 1981 and 1995 were reviewed in a retrospective
      fashion. Of this group, 60 patients were candidates for hearing preservation
      surgery and thus underwent one of two surgical approaches to remove the tumor and
      preserve hearing. Eighteen patients had tumor removal via the middle cranial
      fossa approach, and 42 patients had tumor removed via the retrosigmoid approach.
      Of the 42 patients who underwent retrosigmoid removal, 33% had hearing preserved
      overall. Of the 18 patients in the middle fossa group, 44% had hearing preserved
      overall. The average tumor size of patients with preserved hearing in the
      retrosigmoid group was 1.4 cm, and in the middle fossa group was 0.74 cm. Of
      significance was the fact that in both groups of patients with a tumor of 1.5 cm
      or less there was a 50% chance of hearing preservation. In the group of patients
      with tumors larger than 1.5 cm there was only a 16% chance of preserving hearing.
      We propose that these data can be used for better counseling of patients
      preoperatively as to the chances of hearing preservation and the type of approach
      appropriate for each case.

PMID- 9261020
TI  - Reduction meatoplasty.

PMID- 9261021
TI  - Planned early neck dissection before radiation for persistent neck nodes after
      induction chemotherapy.
AB  - Optimal management of advanced neck metastases as part of an organ preservation
      treatment approach for head and neck squamous carcinoma (HNSC) is unclear. Since
      1989, our management paradigm for patients on organ preservation was modified to
      incorporate planned early neck dissection before radiation therapy for patients
      who did not achieve a complete response (CR) of neck nodes after induction
      chemotherapy (IC). The purpose of this study was to determine if planned early
      neck dissection is a safe and effective approach in the management of advanced
      nodal disease as part of organ preservation. Fifty-eight consecutive patients
      with advanced HNSC who were entered in organ preservation trials using induction
      chemotherapy and radiation with surgical salvage were studied. Median follow-up
      was 26 months. Of the 58 patients, 71% were stage IV. Patients were grouped by
      nodal response to chemotherapy and N class, and were analyzed with respect to
      patterns of recurrence, complications, and survival. Overall, the rate of CR of
      neck nodes was 49%. Fifty-one percent had less than a complete response of neck
      nodes after IC and required planned early neck dissection. There were no
      significant differences in patterns of recurrence, complications, interval time
      to start of radiation, recurrence, or survival rates between the CR and less than
      CR groups. These data suggest that planned early neck dissection for patients
      with less than CR in the neck after IC is not detrimental with respect to neck
      relapse or overall survival. We believe that planned early neck dissection can be
      safely incorporated into future organ preservation treatment protocols for
      patients with advanced head and neck carcinoma.

PMID- 9261022
TI  - Tumor-associated glycoprotein (TAG-72) in chronic submandibular sialadenitis and
      normal minor salivary glands defined by monoclonal antibody B72.3.
AB  - Formalin-fixed, paraffin-embedded samples of three normal minor salivary glands,
      10 chronic submandibular sialadenitis, and three normal submandibular glands were
      studied immunohistochemically using the monoclonal antibody (Mab) B72.3 in order
      to have a better understanding of the distribution of tumor-associated
      glycoprotein (TAG-72). Diffuse expression of TAG-72 was observed in the mucous
      cells of normal minor salivary glands, and in the ducts with goblet cell
      metaplasia and/or hyperplasia of chronic submandibular sialadenitis (eight of
      10). Focal expression of TAG-72 was seen in the acinar mucous cells of normal
      submandibular gland (three of three), and in the mucous cells of normal or
      atrophic acini of chronic submandibular sialadenitis (eight of 10). These results
      should be considered in the cytologic diagnosis of the mucoepidermoid carcinoma
      using the Mab B72.3 as a diagnostic aid, as well as in future studies for the
      radiation immunolocalization and immunotherapy of submandibular gland tumors.

PMID- 9261023
TI  - Platelet aggregation in head and neck tumors in China.
AB  - We measured the maximum aggregation rate (MAR) of platelets in 770 patients with
      malignant head and neck tumors, 55 patients with benign tumors of the head and
      neck, and 164 healthy people as a control group. The results were as follows: 1.
      the mean MAR value of patients with malignant tumors was significantly higher
      than the control group mean value; 2. prior to treatment, the mean MAR value
      increased with advancing tumor stage; 3. both MAR values of relapsed or
      metastasized patients and of nonsurvivors in stage III and IV increased
      significantly compared with survivors or patients recovering from malignant
      tumors. The results of the present study suggest that MAR values of patients with
      malignant tumors of the head and neck may serve as indicators in evaluating
      therapeutic procedures and prognosis.

PMID- 9261024
TI  - Foramen thyroideum: a comparative study in embryos, fetuses, and adults.
AB  - The incidence and characteristics of foramen thyroideum (FT) in embryonic and/or
      fetal larynges have not been established. In the present study, 90 adult larynges
      and 53 embryonic-fetal larynges were studied. The incidence of FT during the
      embryonic-fetal period (57%) was statistically different from the adult period
      (31%) (P = 0.005). All the FT found in the adult period contained vessels and/or
      nerves, while in the embryonic and fetal period only 63% presented neurovascular
      elements (P < 0.001). The origin of FT in the embryonic period and its
      persistence during adult life is discussed.

PMID- 9261025
TI  - Cystic kidneys in children.

PMID- 9261026
TI  - Report from the 1995 Core Indicators for Peritoneal Dialysis Study Group.
AB  - The 1995 Peritoneal Dialysis Core Indicators Study was conducted by the Health
      Care Financing Administration to ascertain standard practices and outcomes in
      chronic peritoneal dialysis patients. Data from 1,202 patients who did not
      receive hemodialysis but who were on chronic ambulatory peritoneal dialysis
      (CAPD) for at least part of the 6-month period between November 1, 1994, and
      April 30, 1995, are reported. The mean serum albumin level for this cohort was
      3.5 g/dL by the bromcresol green method and 3.2 g/dL by the bromcresol purple
      method. Data sufficient to calculate a weekly Kt/V(urea) or weekly creatinine
      clearance were available for only 34% of patient submissions. In these patients,
      the median weekly Kt/V(urea) was 1.7 using a fixed value for V of 0.58 x body
      weight and was 2.0 using the Watson equation to calculate V; the median weekly
      creatinine clearance was 60.7 L/wk/1.73 m2. The mean hematocrit for this cohort
      was 32% and the average weekly recombinant human erythropoietin (rHmEPO) dose was
      115 u/kg. Hematocrit values < or = 30% were found in 50% of black patients and
      31% of white patients. The average blood pressure among peritoneal dialysis
      patients was 139/80 mm Hg, with 29% of patients having a systolic blood pressure
      exceeding 150 mm Hg and 18% a diastolic blood pressure greater than 90 mm Hg. In
      summary, serum albumin levels were significantly lower in peritoneal dialysis
      patients than in hemodialysis patients. Approximately one third of peritoneal
      dialysis patients did not have an adequacy measure obtained during the 6-month
      observation period. A significant minority of patients had either inadequately
      treated anemia of chronic renal disease or hypertension. There is an opportunity
      to substantially improve the medical care provided to chronic peritoneal dialysis
      patients.

PMID- 9261027
TI  - Rapid DNA-based prenatal diagnosis by genetic linkage in three families with
      Alport's syndrome.
AB  - Alport's syndrome (AS) is a clinically and genetically heterogeneous progressive
      inherited glomerulonephritis characterized by hematuria, sensorineural hearing
      loss, ocular lesions, and specific alterations of the glomerular basement
      membrane. Typically, AS shows an X-linked dominant pattern of inheritance, with
      mutations affecting the collagen type IV alpha5 chain gene (COL4A5) at Xq22.
      Rarely, AS is caused in some families by mutations of the COL4A3/A4 genes on
      chromosome 2q, showing an autosomal recessive transmission. Very few families
      have been described with possible autosomal dominant AS, but no mutations in any
      of the COL4 genes have been found. We describe three unrelated families affected
      with a severe AS phenotype in which DNA-based prenatal diagnosis by linkage
      analysis was made in fetuses at risk for the disease. In two families, the
      pedigree structure and the clinical picture were consistent with typical X-linked
      dominant AS. In these families, autosomal inheritance was also ruled out
      molecularly. In one family, despite careful clinical and molecular evaluation,
      the mode of transmission could not be firmly established. We used tightly linked
      and intragenic COL4A5 markers, as well as COL4A3/A4-linked markers. A chromosome
      Y-specific marker for fetal sex determination was simultaneously used. In all the
      families, before the fetal analysis, the putative at-risk X haplotype was
      identified with high diagnostic accuracy. We diagnosed a healthy male fetus in
      one family, and female but carrier fetuses in the other two kindreds, who decided
      not to terminate their pregnancies. We used rapid nonisotopic polymerase chain
      reaction-based methods, and the results were available within 2 to 3 days. The
      genetic results significantly affected the reproductive decisions of the parents.
      This report illustrates the application of genetic linkage analysis as an
      additional tool for molecular diagnosis in AS, and also addresses the issue of
      the attitudes of the families toward prenatal testing. To our knowledge, prenatal
      diagnosis of AS using a genetic linkage approach has not been previously
      reported.

PMID- 9261028
TI  - Exercise training by individuals with predialysis renal failure:
      cardiorespiratory endurance, hypertension, and renal function.
AB  - The purpose of this study was to determine the effects of 4 months of exercise
      training (ET) on cardiorespiratory function and endurance, blood pressure, muscle
      strength, hematology, blood lipids, and renal function in individuals with
      chronic renal failure (CRF) who were not yet on dialysis. Sixteen subjects were
      recruited to volunteer for participation in this study, but only eight completed
      all study phases. Subjects were first evaluated before and after a 2-month
      baseline (BL1 and BL2), after 4 months of ET, and again after 2 months of
      detraining (DT). ET did not change hematology, blood lipids, or echocardiographic
      measurements of left ventricular function and mass. Resting systolic and
      diastolic blood pressures decreased significantly from BL after the ET (146 +/-
      15.7/87 +/- 9 mm Hg to 124 +/- 17.5/78 +/- 9.5 mm Hg; P < 0.02), and then
      increased significantly after DT (139 +/- 14.7 mm Hg and 87 +/- 9.9 mm Hg; P <
      0.01). Peak oxygen consumption (pVO2) changed significantly during the study (1.3
      +/- 0.3 L/min, 1.5 +/- 0.3 L/min, and 1.4 +/- 0.3 L/min for BL2, ET, and DT,
      respectively; P < 0.02), as did the VO2 at the ventilatory threshold (0.65 +/-
      0.18 L/min, 0.92 +/- 0.19 L/min, and 0.68 +/- 0.23 L/min for BL2, ET, and DT,
      respectively; P < 0.01). Knee flexion peak torque increased after ET (43.4 +/-
      25.6 Nm to 51.0 +/- 30.5 Nm; P < 0.02). GFR, as measured by creatinine clearance,
      continued to deteriorate during the course of the study (25.3 +/- 12.0 mL/min,
      21.8 +/- 13.2 mL/min, and 21.8 +/- 13.2 mL/min for BL2, ET, and DT, respectively;
      P < 0.001). Individuals with predialysis CRF who undergo ET improve in functional
      aerobic capacity, muscular strength, and blood pressure.

PMID- 9261029
TI  - Growth rates in pediatric dialysis patients and renal transplant recipients.
AB  - We compared growth rates by modality over a 6- to 14-month period in 1,302 US
      pediatric end-stage renal disese (ESRD) patients treated during 1990. Modality
      comparisons were adjusted for age, sex, race, ethnicity, and ESRD duration using
      linear regression models by age group (0.5 to 4 years, 5 to 9 years, 10 to 14
      years, and 15 to 18 years). Growth rates were higher in young children receiving
      a transplant compared with those receiving dialysis (ages 0.5 to 4 years, delta =
      3.1 cm/yr v continuous cycling peritoneal dialysis [CCPD], P < 0.01; ages 5 to 9
      years, delta = 2.0 to 2.6 cm/yr v CCPD, chronic ambulatory peritoneal dialysis
      (CAPD), and hemodialysis, P < 0.01). In contrast, growth rates in older children
      were not statistically different when comparing transplantation with each
      dialysis modality. For most age groups of transplant recipients, we observed
      faster growth with alternate-day versus daily steroids that was not fully
      explained by differences in allograft function. Younger patients (<15 years) grew
      at comparable rates with each dialysis modality, while older CAPD patients grew
      faster compared with hemodialysis or CCPD patients (P < 0.02). There was no
      substantial pubertal growth spurt in transplant or dialysis patients. This
      national US study of pediatric growth rates with dialysis and transplantation
      shows differences in growth by modality that vary by age group.

PMID- 9261030
TI  - Hemodialysis patient-assessed functional health status predicts continued
      survival, hospitalization, and dialysis-attendance compliance.
AB  - We asked patients to assess their functional health status by completing the SF
      36. Over 2 years, we studied 1,000 patients (average age, 58 years; 50% male; 25%
      white; 36% diabetic) in three outpatient, staff-assisted hemodialysis units. We
      used both the eight-scale scores and two-component summary scores to study the
      relationship between baseline functional health status and clinical outcomes. The
      physical component summary (PCS) score was as significant a predictor of
      mortality as was the normalized protein catabolic rate or the delivered Kt/V.
      Patients with a PCS score below the median for our patients (< 34) were twice as
      likely to die and 1.5 times more likely to be hospitalized as patients with PCS
      scores at or above the median score. Either a low PCS score or a low mental
      component summary (MCS) score correlated with the number of days of
      hospitalization. While the average dialysis patient has a relatively normal (47 v
      50) MCS score and a low (37 v 50) PCS score compared with the normal population,
      patients who skipped more than two treatments per month tended to have a
      relatively higher PCS score (judged themselves physically healthier) and a
      relatively lower MCS score (judged themselves less mentally healthy) than
      patients who did not skip two or more treatments per month. The prevalence of
      depression as defined by an MCS score of < or = 42 was approximately 25%. The SF
      36 provided a good screening tool for patients at high risk for death,
      hospitalization, poor attendance, and depression.

PMID- 9261031
TI  - Long-term performance and complications of the Tesio twin catheter system for
      hemodialysis access.
AB  - The Tesio twin catheter system (Medcomp, Harleysville, PA) was developed to
      overcome the problems with the existing central venous catheters in providing
      high-efficiency dialysis, such as inadequate blood flows, high recirculation
      rates, and need for surgical insertion. The relatively large internal lumens and
      multiple side holes in a spiral pattern allow for high blood flow rates and lower
      tendency to thrombosis. In this series, 82 catheter pairs were placed in 75
      patients and monitored for a period encompassing 231 patient-months. We achieved
      mean nominal blood pump flow rates of 400 +/- 6 mL/min and an average
      recirculation of 4.6% +/- 0.5%. In 20 sets of catheters, a nominal blood flow
      rate of 388 +/- 6 mL/min was measured ultrasonically at 352 +/- 8 mL/min,
      representing an error of 36 +/- 5 mL/min. Thrombosis of the catheter occurred at
      a rate of one episode per 21 patient-months, and on all occasions responded to
      local instillation of urokinase. Despite having two exit sites, the infection
      rates were comparable to other catheters: exit site infections occurred at a rate
      of one per 21 patient-months and bacteremic episodes occurred at one per 11.5
      patient-months, necessitating catheter removal once per 46 patient-months. Based
      on these data, we believe that the Tesio twin catheter system is an excellent
      long- and short-term vascular access for providing high-efficiency dialysis.

PMID- 9261032
TI  - Autonomic neuropathy predisposing to arrhythmias in hemodialysis patients.
AB  - Arrhythmias are frequent among the dialysis population and can cause symptoms of
      palpitations or dizziness. Since autonomic disturbances are known to cause an
      increased arrhythmogenic stimulus, we questioned whether the presence of central
      autonomic neuropathy increased the frequency of arrhythmias as identified by 24
      hour electrocardiographic monitoring in dialysis patients. Seventy-one patients
      were randomly chosen from patients established on dialysis in two centers. The
      mean age of the patients was 71.3 years (median age, 67 years) and median
      duration on dialysis was 17.0 months (range, 1 to 175 months). Four patients had
      diabetes. Each patient was tested for autonomic control of blood pressure and
      heart rate, and underwent Holter electrocardiographic monitoring, commencing 30
      minutes before dialysis, for a 24-hour period. The tapes were then analyzed for
      ventricular and atrial rhythm changes. There was a significantly increased
      incidence of arrhythmias in individuals with abnormal blood pressure responses (P
      = 0.005), heart rate responses (P = 0.01), and combined blood pressure and heart
      rate responses (P = 0.004). We conclude that patients with autonomic dysfunction
      had an increased frequency of arrhythmias during dialysis.

PMID- 9261033
TI  - Elderly patients in chronic hemodialysis: risk factors for left ventricular
      hypertrophy.
AB  - In the past few years in Western countries, there has been an increasing
      proportion of elderly patients beginning renal replacement therapy. Left
      ventricular hypertrophy (LVH) is associated with an increased mortality rate due
      to cardiovascular disease, the main cause of death in patients on chronic
      hemodialysis. In this study, we evaluated 67 chronic hemodialysis patients older
      than 65 years (33 women and 34 men; mean age, 72.6 years; mean time on chronic
      hemodialysis, 51.3 months). Several biological and laboratory data were analyzed.
      The left ventricular mass was calculated using the Penn convention criteria. LVH
      was observed in 49 patients (73%). These 49 patients were divided into two groups
      (group 1, concentric hypertrophy, n = 22; and group 2, eccentric hypertrophy, n =
      27) and compared with a control group (patients without LVH, n = 18). Group 1 (P
      = 0.06) and group 2 (P = 0.055) showed higher systolic blood pressures and group
      2 showed a lower hematocrit (P = 0.024). The echocardiographic parameters were
      expectedly different: group 1 had higher posterior left ventricular wall
      thickness (P = 0.0001), interventricular septum thickness (P = 0.0001), and left
      ventricular wall relative thickness (P = 0.002), and group 2 had higher left
      ventricular end-diastolic diameter (P = 0.0001), interventricular septum
      thickness (P = 0.01), and posterior left ventricular wall thickness (P = 0.023).
      Using the left ventricular mass index as the dependent variable and the evaluated
      biological and laboratory data as the independent variables, we found in a
      stepwise multiple regression model that only systolic blood pressure (t = 3.430;
      P = 0.0011), age (t = 2.059; P = 0.044), interdialytic weight gain (t = 2.236; P
      = 0.029), and hematocrit (t = -1.961; P = 0.054) independently influenced the
      left ventricular mass index (R2 = 0.313; P = 0.0001). Further studies are needed
      to determine whether reduction of the left ventricular mass index, through
      control of blood pressure and correction of anemia, will decrease the
      cardiovascular events in this particular population.

PMID- 9261034
TI  - Peritoneal transport kinetics correlate with serum albumin but not with the
      overall nutritional status in CAPD patients.
AB  - The present study evaluates the influence of the peritoneal transport rate (PTR)
      on the nutritional status of continuous ambulatory peritoneal dialysis (CAPD)
      patients. Additionally, protein intake, dialysis adequacy, and other clinical
      variables were analyzed. Forty-two CAPD patients were concurrently subjected to
      the peritoneal equilibration test, a nutritional evaluation that included 24-hour
      dietary recall, and nutritional scoring system that included anthropometric,
      biochemical, and subjective parameters. Eight patients were high, 14 were high
      average, 16 were low-average, and four were low transporters. Nine patients had
      normal nutritional status; six had mild, nine had moderate, and 18 had severe
      malnutrition. Malnutrition was inversely correlated (P < 0.05) with body surface,
      hemoglobin, and residual renal function, but not with PTR (r = 0.14; P = 0.38).
      In the multivariate analysis, the nutritional status was not predicted by the
      PTR, protein intake, or dialysis adequacy variables. When serum albumin (SA)
      level was evaluated as an isolated nutritional indicator, the most significant
      predictors were dialysate to plasma creatinine ratio at 4 hours (D/P4), body
      surface area, age, and diabetes mellitus. High transporters receiving a high dose
      of dialysis displayed a trend of having lower SA levels, whereas low-average
      transporters receiving a high dose of dialysis showed a trend of have higher SA
      levels. In conclusion, there was no correlation between PTR and nutritional
      status. In the multivariate analysis, no association was found between
      nutritional status and PTR, dialysis adequacy, and protein intake. The best
      predictors for SA are PTR, body surface area, age, and diabetes mellitus.

PMID- 9261035
TI  - Ammonium acid urate crystal formation in adult North American stone-formers.
AB  - Although ammonium acid urate (AAU) stones are endemic in Asia, pure AAU calculi
      have almost disappeared from industrialized countries and clinical
      pathophysiologic relevance of sporadic stones containing AAU crystals is
      currently unknown. We reviewed 1,396 crystallographic stone analyses performed in
      our institution over a 10-year period. Prevalence of stones containing AAU
      crystals and predominantly AAU stones were 3.1% and 0.2%, respectively. In more
      than two thirds of cases, AAU crystals represented less than 10% of stone crystal
      composition. No pure AAU stone was found. According to crystalline predominance,
      42%, 35%, and 12% of these calculi were uric acid, infectious, and calcium
      oxalate stones, respectively. AAU crystals were detected as discrete
      intercrystalline or peripheral deposits in 74.4% of stones. In only one calculus
      was AAU crystals detected in the nucleus. The hospital charts of 37 patients who
      presented with 43 calculi containing AAU crystals were also reviewed. The mean
      age was 53.1 +/- 16.6 years. Fifty-seven percent of calculi were upper urinary
      tract stones and 43% were bladder stones. Upper urinary tract calculi were more
      frequently uric acid stones, followed by infectious and calcium oxalate stones.
      Lower urinary tract calculi were more frequently infectious stones, followed by
      uric acid stones. Upper urinary tract stones were passed spontaneously in 13
      patients and removed surgically in nine patients. Nine of these subjects were
      idiopathic recurrent stone formers who had passed other calculi with no trace of
      AAU crystal. Fifty-seven percent of lower urinary tract stones were associated
      with documented bladder dysfunction. In conclusion, although AAU-containing
      urolithiases are occasionally seen in our population, predominantly or primarily
      AAU stones are exceptional. AAU crystal formation usually appears as a minor and
      secondary phenomenon of no primary pathophysiologic relevance in stone formation.

PMID- 9261036
TI  - Effect of enalapril therapy on glomerular accumulation of immune complexes and
      mesangial matrix in experimental glomerulonephritis in the nonhuman primate.
AB  - The present study is a prospective, controlled, blinded trial of enalapril
      therapy in experimental immune complex (IC)-mediated glomerulonephritis (GN) in
      the nonhuman primate (cynomolgus monkey [CYN]). Two groups of CYNs were studied:
      those with established GN (study A) and those in which GN was being induced
      (study B). In study A, 12 CYNs had GN established by 8 or 10 weeks of daily
      intravenous infusion of bovine gamma-globulin (BGG). These CYNs were then
      assigned to either 4 weeks of daily oral enalapril therapy (n = 6) or daily oral
      placebo therapy (n = 6). The daily BGG infusions were continued during the 4
      weeks of enalapril or placebo therapy. At the start of the enalapril/placebo
      protocol, the two groups were similar with respect to proteinuria and level of
      precipitating antibody to BGG, which determined the daily BGG dose. Renal biopsy
      was performed in each CYN at the start and end of the 4-week period of
      enalapril/placebo protocol. In study B, 15 normal CYNs were immunized to BGG over
      a period of 4 weeks. The CYNs were then assigned to daily oral enalapril therapy
      (n = 8) or placebo therapy (n = 7) based on level of precipitating antibody to
      BGG. At this point, daily intravenous BGG was begun along with daily enalapril or
      placebo for 8 weeks. Renal biopsy was performed in each CYN before and at the end
      of this 8-week period. In study A, enalapril therapy was associated with a
      significant decrease in mesangial matrix volume (mean change, -27.7%; P = 0.031)
      and a trend toward decreased mesangial matrix deposits (mean change, -34.1%; P =
      0.188). By contrast, in CYNs receiving placebo therapy, mesangial matrix volume
      increased compared with the enalapril group (P = 0.002) and mesangial deposits
      were unchanged. In study B, both the enalapril and placebo groups showed
      significant increases in mesangial matrix volume, mesangial deposits, mesangial
      cell volume, and capillary wall deposits during the 8 weeks of daily BGG
      infusion. However, none of the differences between the groups achieved
      statistical significance. Changes in mesangial cell volume and capillary wall
      deposits were also evaluated in study A and study B, but were not found to be
      different between the enalapril and placebo groups. In both study A and study B,
      blood pressure was lower in the enalapril groups. In conclusion, in the initial
      phase of IC-GN induction (0 to 8 weeks), enalapril therapy does not significantly
      influence the glomerular accumulation of mesangial matrix or immune deposits.
      However, in established IC-GN (after 8 weeks of GN induction), enalapril therapy
      significantly decreases the further accumulation of mesangial matrix and may
      decrease the further accumulation of mesangial deposits. Whether this benefit of
      enalapril therapy was related to lower blood pressure or to other effects of
      angiotensin-converting enzyme (ACE) inhibition was not determined in this study.

PMID- 9261037
TI  - Aminoguanidine prolongs survival in azotemic-induced diabetic rats.
AB  - Toxic effects of hyperglycemia-induced advanced glycosylated end products (AGEs)
      may explain some vasculopathic complications of diabetes. Aminoguanidine, a known
      inhibitor of AGE formation, was administered by gavage to Sprague-Dawley
      streptozotocin-induced diabetic rats made azotemic by surgical reduction of renal
      mass. All rats became hyperglycemic. Renal ablation caused renal insufficiency,
      as evidenced by markedly reduced endogenous creatinine clearances at days 7 and
      14. Aminoguanidine-treated rats had significantly (P < 0.04) superior survival to
      that of untreated azotemic diabetic rats. We infer from the extended life in a
      rat model of uremia in diabetic nephropathy that aminoguanidine may prove
      beneficial in human diabetes.

PMID- 9261038
TI  - Association of IgA nephropathy with T-cell receptor constant alpha chain gene
      polymorphism.
AB  - T-cell receptor (TCR) proteins recognize a complex of an antigen-derived peptide
      bound to the cell surface products of the major histocompatibility complex (MHC)
      that could be of importance in the immunopathogenesis of IgA nephropathy (IgAN).
      Previous studies found no difference on TCR constant beta chain gene frequencies
      in IgAN compared with control. Yet no study on the TCR alpha gene in IgAN was
      reported. We studied the TCR C alpha gene polymorphisms by restriction fragment
      length polymorphism (RFLP) in 53 patients with IgAN and in comparison with 67
      healthy controls. The patients were also classified into different
      histopathological grading (I, II, and III with increasing histological severity)
      and renal functions. The extracted DNA were digested with Taq I enzymes and
      probed with a full-length TCR-alpha cDNA clone p1.2alpha probe. A 7-kb C-alpha
      Taq 1 fragment is found in 32 of 53 patients (60.3%) compared with 26 of 67
      controls (38.8%) (P < 0.05). There was no association of any polymorphic
      fragment, including the 7-kb fragment, with either the histological grading or
      renal function. It is concluded that the TCR C-alpha gene is associated with IgAN
      but not with the prognosis of the disease.

PMID- 9261040
TI  - Focal segmental glomerulosclerosis in one of two "en bloc" pediatric transplanted
      kidneys.
AB  - Focal segmental glomerulosclerosis (FSGS) is thought to have several causes,
      including hypertension, reduction of nephron mass, or immunologic processes.
      Experimental studies have underlined the role of glomerular adaptation to
      capillary pressure in the growing kidney after partial nephrectomy. We report
      here the occurrence of FSGS in one of two "en bloc" pediatric kidneys
      transplanted in an adult recipient. One of the kidneys sustained early ureteral
      obstruction requiring reoperation and subsequently developed pathological changes
      on biopsy consistent with FSGS, whereas the mate kidney did not, although both
      kidneys grew at equal rates and to equivalent sizes.

PMID- 9261041
TI  - A case of a dialysis patient with sclerosing peritonitis successfully treated
      with corticosteroid therapy alone.
AB  - Sclerosing peritonitis (SCP) is a rare complication of peritoneal dialysis. Most
      of the patients with this serious complication have been treated in a symptomatic
      and conservative manner. Other patients have undergone risky surgical
      interventions. Recently it was reported that immunosuppressive therapy after
      renal transplantation was effective for this complication. A 56-year-old man
      developed sclerosing peritonitis 5 months after switching from peritoneal
      dialysis to hemodialysis because of ultrafiltration failure. The patient had
      ongoing inflammatory signs and symptoms, and corticosteroid therapy was
      commenced. His condition was dramatically improved within 1 week, and he is now
      well on an outpatient basis with the maintenance dosage of corticosteroid. This
      is the first report of a patient with peritoneal dialysis-related SCP who
      responded favorably to corticosteroid therapy alone.

PMID- 9261039
TI  - Familial focal segmental glomerulosclerosis: nine cases in four families and
      review of the literature.
AB  - Idiopathic focal segmental glomerulosclerosis (FSGS) is a common cause of
      glomerular disease. Although previous case reports suggesting a familial form of
      the disease exist in the literature, its significance has not been emphasized. We
      report on our experience with nine cases in four families, as well as a review of
      the literature, and provide evidence that a familial form of FSGS might represent
      a distinct genotypic and phenotypic subset of idiopathic FSGS.

PMID- 9261042
TI  - Scleroderma, D-penicillamine treatment, and progressive renal failure associated
      with positive antimyeloperoxidase antineutrophil cytoplasmic antibodies.
AB  - Progressive renal failure in patients with scleroderma is a sinister development
      that is usually attributed to impaired renal blood flow. In some exceptional
      cases, the underlying pathology is a crescentic glomerulonephritis, which has
      been associated with positive antineutrophil cytoplasmic antibodies, and in
      particular antimyeloperoxidase antibodies. The prognosis in such cases has been
      very poor. We report such a patient whose renal function has improved and
      stabilized on immunosuppressive therapy.

PMID- 9261043
TI  - End-stage renal failure from mushroom poisoning with Cortinarius orellanus:
      report of four cases and review of the literature.
AB  - Mushrooms of the ubiquitous Cortinarius species (Cs) contain nephrotoxins that
      can cause acute and chronic renal failure by an unknown pathomechanism. Typical
      is a long symptom-free interval before the onset of clinical disease. A causal
      form of therapy is not known. Early hemodialysis can improve the prognosis of
      this potentially life-threatening condition. Diagnosis of Cs poisoning can be
      made by detecting the responsible toxin--orellanine--in plasma or renal tissue by
      fluorimetry after thin-layer chromatography or by identifying the spores of left
      over mushrooms as Cs. Renal histology shows nonspecific changes such as tubular
      dilatation and flattening of the epithelium and signs of interstitial edema
      followed by interstitial fibrosis. We present four cases of Cs poisoning with
      different outcomes and a review of the literature.

PMID- 9261045
TI  - Discontinuing dialysis in persistent vegetative state: the roles of autonomy,
      community, and professional moral agency.
AB  - This report proposes a policy for discontinuing dialysis in persistent vegetative
      state (PVS) patients and attempts to address autonomy and community-based values
      while maintaining professional moral agency. It is recommended that the policy be
      adopted at a regional level (eg, the ESRD Network). The involved physicians and
      ethicists would communicate with the next-of-kin and surrogate decision-makers,
      and the local ethics committee would perform a double review of the case to
      assure the appropriateness of the policy to the case. Given the unique nature of
      PVS with its permanent loss of consciousness and autonomy, we hold that a
      community-based consensus can form a guideline that limits futile dialysis while
      respecting patient and professional moral agency. Prior consent of dialysis
      patients to the regional policy at a time shortly after initiating dialysis will
      add to its ethical impetus.

PMID- 9261046
TI  - Dietary protein restriction and progressive renal insufficiency.

PMID- 9261044
TI  - Elimination study of silver in a hemodialyzed burn patient treated with silver
      sulfadiazine cream.
AB  - Silver sulfadiazine (SSD) cream is a potent agent for the treatment of burns. In
      a patient with end-stage renal disease, we observed a marked elevation in serum
      silver concentration in the course of 2 weeks of SSD cream therapy (200 g/d).
      Serum concentration of silver reached a maximum of 291 ng/mL in association with
      a rapid deterioration of mental status. SSD therapy was discontinued, and
      hemodialysis, hemofiltration, or plasma exchange was continually performed. Four
      months later, the patient died. At autopsy, profoundly elevated levels of silver
      were found in brain tissues of this patient (617.3, 823.7 ng/g wet tissue weight
      in the cerebrum and cerebellum, respectively). To determine the most efficient
      therapy to remove silver from serum, we compared hemodialysis (HD),
      hemofiltration (HF), and plasma exchange (PE). Both plasma exchange and
      hemofiltration were effective in decreasing serum silver, and their effects were
      additive. By contrast, HD was ineffective in reducing serum silver. This case
      illustrates that, on SSD cream therapy, burn patients with disturbed renal
      function are at risk of accumulating silver in serum and tissue to the level that
      may cause neuralgic decompensation. Removal of serum silver can best be effected
      by PE, particularly when combined with HF. In contrast, HD per se does not appear
      efficacious. None of these blood purification modalities improves deterioration
      of neurological status potentially attributable to silver deposition in brain
      tissues.

PMID- 9261047
TI  - Posttransplantation lymphoproliferative disorder in a renal allograft recipient.
AB  - As a complication of immunosuppressive therapy, solid organ and bone marrow
      transplant recipients have an increased risk of developing post transplant
      lymphoproliferative disorder (PTLD). Epstein-Barr virus (EBV) infection and the
      degree of immunosuppression have been identified as risk factors for the
      development of this complication. The clinical presentation includes a spectrum
      of disorders ranging from a benign infectious mononucleosis-like syndrome with
      fever and cervical adenopathy to multiorgan failure leading to death. Although, T
      cell lesions have been described, PTLD is usually associated with a polyclonal or
      monoclonal B-cell proliferation. In this report, we present a renal transplant
      recipient with a perirenal mass diagnosed as PTLD.

PMID- 9261048
TI  - Albumin trend and mortality.

PMID- 9261049
TI  - The trans-Golgi network: a late secretory sorting station.
AB  - Proteins synthesized on membrane-bound ribosomes are transported through the
      Golgi apparatus and, on reaching the trans-Golgi network, are sorted for delivery
      to various cellular destinations. Sorting involves the assembly of cytosol
      oriented coat structures which preferentially package cargo into vesicular
      transport intermediates. Recent studies have shed new light on both the molecular
      machinery involved and the complexity of the sorting processes.

PMID- 9261050
TI  - SNAREs and NSF in targeted membrane fusion.
AB  - A major current issue in vesicle trafficking is whether NSF (N-ethylmaleimide
      sensitive factor) and alpha-SNAP (alpha-soluble NSF attachment protein) are
      required prior to SNARE (SNAP receptor) complex formation to allow vesicle
      docking, or after docking at a step close to membrane fusion. Recent studies of
      yeast vacuolar fusion indicated that the requirement for ATP, NSF and alpha-SNAP
      could be completely satisfied prior to SNARE docking complex assembly; however,
      the universality of a predocking role for these factors remains to be
      established. The vacuolar fusion system has also been used to directly
      demonstrate a requirement for SNARE proteins on both fusing membranes, verifying
      a central postulate of current fusion models.

PMID- 9261051
TI  - The cystic fibrosis transmembrane conductance regulator and ATP.
AB  - A controversy in the field of cystic fibrosis (CF) research has arisen concerning
      the role of the cystic fibrosis transmembrane conductance regulator (CFTR) in the
      transport of ATP. Does the CFTR actually conduct ATP or does it regulate the
      conductance of ATP? Recent findings either support or reject the hypothesis that
      the CFTR can transport ATP. In addition, recent research from several
      laboratories has suggested that ATP mediates its effects after traversing the
      plasma membrane and reaching the extracellular surface. The current model
      suggests that the released ATP exerts its various influences via a purinergic
      receptor to regulate outwardly rectifying chloride channels and epithelial sodium
      channels.

PMID- 9261052
TI  - COPII and secretory cargo capture into transport vesicles.
AB  - Yeast cylosolic coat proteins (COPII) direct the formation of vesicles from the
      endoplasmic reticulum. The vesicles selectively capture both cargo molecules and
      the secretory machinery that is necessary for the fusion of the vesicle with the
      recipient compartment, the Golgi apparatus. Recent efforts have aimed to
      understand how proteins are selected for inclusion into these vesicles. A variety
      of cargo adaptors may concentrate and sort secretory and membrane proteins by
      direct or indirect interaction with a subset of coat protein subunits.

PMID- 9261053
TI  - Coatomer (COPI)-coated vesicles: role in intracellular transport and protein
      sorting.
AB  - Coatomer-coated vesicles have been proposed to play a role in many distinct steps
      of intracellular transport. Coatomer potentially plays a role in forward
      transport from the endoplasmic reticulum to the Golgi apparatus and through the
      Golgi apparatus. It may also function in retrograde transport and in the
      endocytic pathway. There are limitations to the various approaches used to study
      the role of coatomer, and looking at these helps us to better define the
      questions that remain to be answered.

PMID- 9261054
TI  - The ABCs of ATP-sensitive potassium channels: more pieces of the puzzle.
AB  - ATP-sensitive potassium channels, KATP channels are critical for the normal
      regulation of insulin secretion. The cloning of cDNAs encoding the subunits of
      these channels shows that they are a novel combination of an ATP-binding protein
      and a small inward rectifier. Loss of pancreatic beta-cell KATP channels has been
      shown to cause familial hyperinsulinism.

PMID- 9261055
TI  - Linking cargo to vesicle formation: receptor tail interactions with coat
      proteins.
AB  - How soluble cargo molecules concentrate into budding vesicles is the subject of
      intensive current research. Clathrin-based vesiculation from the plasma membrane
      and the trans-Golgi network constitutes the best described system that supports
      this sorting process. Soluble ligands bind to specific transmembrane receptors
      which have been shown to interact directly with clathrin adaptor complexes,
      components of clathrin coats. At the same time, these clathrin adaptors
      facilitate clathrin coat assembly and probably regulate the recruitment of the
      rest of the coat components. Recent studies have looked at both the interaction
      of receptor tails with adaptors and the assembly of the clathrin coat. Progress
      has also been made in elucidating how soluble cargo molecules may be concentrated
      for exit from the endoplasmic reticulum.

PMID- 9261056
TI  - Regulation of aquaporin-2 water channel trafficking by vasopressin.
AB  - Vasopressin regulates water excretion from the kidney by increasing the osmotic
      water permeability of the renal collecting duct. The aquaporin-2 water channel
      has been demonstrated to be the target for this action of vasopressin. Recent
      studies have demonstrated that vasopressin, acting through cyclic AMP, triggers
      fusion of aquaporin-2-bearing vesicles with the apical plasma membrane of the
      collecting duct principal cells. The vesicle-targeting proteins synaptobrevin-2
      and syntaxin-4 are proposed to play roles in this process.

PMID- 9261057
TI  - Calcium regulation of neurotransmitter release: reliably unreliable?
AB  - Recent studies of central synaptic transmission reveal that neurotransmitter
      release is more unreliable than was previously thought. Nerve stimulation does
      not always elicit transmitter release, and when release events occur vesicle
      fusion with the presynaptic membrane is limited to at most a single quantum.

PMID- 9261058
TI  - The role of lipid signaling in constitutive membrane traffic.
AB  - Several lines of evidence indicate that enzymes that modify membrane lipids
      function in the regulation of constitutive membrane traffic. Recent evidence
      suggests that specific phosphatidylinositides may regulate the activity of
      proteins with diverse functions in membrane transport, such as dynamin, the
      clathrin-associated AP-2 complex, and proteins that stimulate guanine nucleotide
      exchange on ADP-ribosylation factors (ARFs). ARF proteins activate a
      phospholipase D that produces phosphatidic acid from phosphatidylcholine, and
      this may be essential for the formation of certain types of transport vesicles or
      may be constitutive vesicular transport to signal transduction pathways.

PMID- 9261059
TI  - Family of neutral and acidic amino acid transporters: molecular biology,
      physiology and medical implications.
AB  - Glutamate transporters and structurally related neutral amino acid transporters
      constitute a distinct family of Na(+)-dependent transporters. The different
      transporters of this family share similar structural traits, and exhibit
      different yet comparable functions. Significant recent advances in our
      understanding of the structure and function of these transporters include: a new
      twist in our knowledge of ion-coupling stoichiometry; the knockout of glutamate
      transporters, which reveals a major role for glial glutamate transporters; and
      new insights into the regulation of glutamate transporter expression.

PMID- 9261060
TI  - Caveolae, DIGs, and the dynamics of sphingolipid-cholesterol microdomains.
AB  - There is accumulating evidence that lateral assemblies (rafts) of sphingolipids
      and cholesterol form platforms that serve to support numerous cellular events in
      membrane traffic and signal transduction. Raft membrane microdomains are thought
      to function by preferentially associating with specific proteins while excluding
      others. The basic forces driving raft formation are lipid interactions which are,
      per se, weak and transient. Sphingolipid rafts should therefore be considered to
      be dynamic structures in which cholesterol plays an important role as a linker.
      Caveolins influence these dynamics by forming stabilized raft domains in
      intracellular membranes as well as at the plasma membrane. Recent data suggest
      that clustering of raft components could regulate raft dynamics and therefore
      represents an important feature in the function of these membrane microdomains.

PMID- 9261062
TI  - Membranes and sorting.

PMID- 9261061
TI  - The diversity of Rab proteins in vesicle transport.
AB  - Rab proteins have been primarily implicated in vesicle docking as regulators of
      SNARE pairing. Recent findings, however, indicate that their function in vesicle
      trafficking can go beyond this role, and a number of proteins, unrelated to each
      other, have been identified as putative Rab effectors. Although the GTPase switch
      of Rab proteins is highly conserved, functional mechanisms may be highly
      diversified among members of the Rab family.

PMID- 9261064
TI  - Membranes and sorting. Membrane permeability.

PMID- 9261063
TI  - Membrane permeability. The diversity of transmembrane transport processes.

PMID- 9261065
TI  - Neutral networks in protein space: a computational study based on knowledge-based
      potentials of mean force.
AB  - BACKGROUND: Many protein sequences, often unrelated, adopt similar folds.
      Sequences folding into the same shape thus form subsets of sequence space. The
      shape and the connectivity of these sets have implications for protein evolution
      and de novo design. RESULTS: We investigate the topology of these sets for some
      proteins with known three-dimensional structure using inverse folding techniques.
      First, we find that sequences adopting a given fold do not cluster in sequence
      space and that there is no detectable sequence homology among them. Nevertheless,
      these sequences are connected in the sense that there exists a path such that
      every sequence can be reached from every other sequence while the fold remains
      unchanged. We find similar results for restricted amino acid alphabets in some
      cases (e. g. ADLG). In other cases, it seems impossible to find sequences with
      native-like behavior (e.g. QLR). These findings seem to be independent of the
      particular structure considered. CONCLUSIONS: Amino acid sequences folding into a
      common shape are distributed homogeneously in sequence space. Hence, the
      connectivity of the set of these sequences implies the existence of very long
      neutral paths on all examined protein structures. Regarding protein design, these
      results imply that sequences with more or less arbitrary chemical properties can
      be attached to a given structural framework. But we also observe that
      designability varies significantly among native structures. These features of
      protein sequence space are similar to what has been found for nucleic acids.

PMID- 9261066
TI  - The structure of Staphylococcus aureus epidermolytic toxin A, an atypic serine
      protease, at 1.7 A resolution.
AB  - BACKGROUND: Staphylococcal epidermolytic toxins A and B (ETA and ETB) are
      responsible for the staphylococcal scalded skin syndrome of newborn and young
      infants; this condition can appear just a few hours after birth. These toxins
      cause the disorganization and disruption of the region between the stratum
      spinosum and the stratum granulosum--two of the three cellular layers
      constituting the epidermis. The physiological substrate of ETA is not known and,
      consequently, its mode of action in vivo remains an unanswered question.
      Determination of the structure of ETA and its comparison with other serine
      proteases may reveal insights into ETA's catalytic mechanism. RESULTS: The
      crystal structure of staphylococcal ETA has been determined by multiple
      isomorphous replacement and refined at 1.7 A resolution with a crystallographic R
      factor of 0.184. The structure of ETA reveals it to be a new and unique member of
      the trypsin-like serine protease family. In contrast to other serine protease
      folds, ETA can be characterized by ETA-specific surface loops, a lack of cysteine
      bridges, an oxyanion hole which is not preformed, an S1 specific pocket designed
      for a negatively charged amino acid and an ETA-specific specific N-terminal helix
      which is shown to be crucial for substrate hydrolysis. CONCLUSIONS: Despite very
      low sequence homology between ETA and other trypsin-like serine proteases, the
      ETA crystal structure, together with biochemical data and site-directed
      mutagenesis studies, strongly confirms the classification of ETA in the Glu
      endopeptidase family. Direct links can be made between the protease architecture
      of ETA and its biological activity.

PMID- 9261067
TI  - MAD analysis of FHIT, a putative human tumor suppressor from the HIT protein
      family.
AB  - BACKGROUND: The fragile histidine triad (FHIT) protein is a member of the large
      and ubiquitous histidine triad (HIT) family of proteins. It is expressed from a
      gene located at a fragile site on human chromosome 3, which is commonly disrupted
      in association with certain cancers. On the basis of the genetic evidence, it has
      been postulated that the FHIT protein may function as a tumor suppressor,
      implying a role for the FHIT protein in carcinogenesis. The FHIT protein has
      dinucleoside polyphosphate hydrolase activity in vitro, thus suggesting that its
      role in vivo may involve the hydrolysis of a phosphoanhydride bond. The
      structural analysis of FHIT will identify critical residues involved in substrate
      binding and catalysis, and will provide insights into the in vivo function of HIT
      proteins. RESULTS: The three-dimensional crystal structures of free and
      nucleoside complexed FHIT have been determined from multiwavelength anomalous
      diffraction (MAD) data, and they represent some of the first successful
      structures to be measured with undulator radiation at the Advanced Photon Source.
      The structures of FHIT reveal that this protein exists as an intimate homodimer,
      which is based on a core structure observed previously in another human HIT
      homolog, protein kinase C interacting protein (PKCI), but has distinctive
      elaborations at both the N and C termini. Conserved residues within the HIT
      family, which are involved in the interactions of the proteins with nucleoside
      and phosphate groups, appear to be relevant for the catalytic activity of this
      protein. CONCLUSIONS: The structure of FHIT, a divergent HIT protein family
      member, in complex with a nucleotide analog suggests a metal-independent
      catalytic mechanism for the HIT family of proteins. A structural comparison of
      FHIT with PKCI and galactose-1-phosphate uridylyltransferase (GaIT) reveals
      additional implications for the structural and functional evolution of the
      ubiquitous HIT family of proteins.

PMID- 9261068
TI  - A biopolymer by any other name would bind as well: a comparison of the ligand
      binding pockets of nucleic acids and proteins.
AB  - Crystal structures have recently been reported for several in vitro selected
      aptamers that bind small molecules. A structural comparison of these aptamers
      with proteins that bind identical ligands reveals similar strategies for forming
      ligand-binding pockets.

PMID- 9261069
TI  - The structure of enzyme IIAlactose from Lactococcus lactis reveals a new fold and
      points to possible interactions of a multicomponent system.
AB  - BACKGROUND: The bacterial phosphoenolpyruvate: sugar phosphotransferase system
      (PTS) is responsible for the binding, transmembrane transport and phosphorylation
      of numerous sugar substrates. The system is also involved in the regulation of a
      variety of metabolic and transcriptional processes. The PTS consists of two non
      specific energy coupling components, enzyme I and a heat stable phosphocarrier
      protein (HPr), as well as several sugar-specific multiprotein permeases known as
      enzymes II. In most cases, enzymes IIA and IIB are located in the cytoplasm,
      while enzyme IIC acts as a membrane channel. Enzyme IIAlactose belongs to the
      lactose/cellobiose-specific family of enzymes II, one of four functionally and
      structurally distinct groups. The protein, which normally functions as a trimer,
      is believed to separate into its subunits after phosphorylation. RESULTS: The
      crystal structure of the trimeric enzyme IIAlactose from Lactococcus lactis has
      been determined at 2.3 A resolution. The subunits of the enzyme, related to each
      other by the inherent threefold rotational symmetry, possess interesting
      structural features such as coiled-coil-like packing and a methionine cluster.
      The subunits each comprise three helices (I, II and III) and pack against each
      other forming a nine-helix bundle. This helical bundle is stabilized by a
      centrally located metal ion and also encloses a hydrophobic cavity. The three
      phosphorylation sites (His78 on each monomer) are located in helices III and
      their sidechains protrude into a large groove between helices I and II of the
      neighbouring subunits. A model of the complex between phosphorylated HPr and
      enzyme IIAlactose has been constructed. CONCLUSIONS: Enzyme IIAlactose is the
      first representative of the family of lactose/cellobiose-specific enzymes IIA for
      which a three-dimensional structure has been determined. Some of its structural
      features, like the presence of two histidine residues at the active site, seem to
      be common to all enzymes no overall structural homology is observed to any PTS
      proteins or to any other proteins in the Protein Data Bank. Enzyme IIAlactose
      shows surface complementarity to the phosphorylated form of HPr and several
      energetically favourable interactions between the two molecules can be predicted.

PMID- 9261070
TI  - Structure of bacteriophage T4 fibritin: a segmented coiled coil and the role of
      the C-terminal domain.
AB  - BACKGROUND: Oligomeric coiled-coil motifs are found in numerous protein
      structures; among them is fibritin, a structural protein of bacteriophage T4,
      which belongs to a class of chaperones that catalyze a specific phage-assembly
      process. Fibritin promotes the assembly of the long tail fibers and their
      subsequent attachment to the tail baseplate; it is also a sensing device that
      controls the retraction of the long tail fibers in adverse environments and,
      thus, prevents infection. The structure of fibritin had been predicted from
      sequence and biochemical analyses to be mainly a triple-helical coiled coil. The
      determination of its structure at atomic resolution was expected to give insights
      into the assembly process and biological function of fibritin, and the properties
      of modified coiled-coil structures in general. RESULTS: The three-dimensional
      structure of fibritin E, a deletion mutant of wild-type fibritin, was determined
      to 2.2 A resolution by X-ray crystallography. Three identical subunits of 119
      amino acid residues form a trimeric parallel coiled-coil domain and a small
      globular C-terminal domain about a crystallographic threefold axis. The coiled
      coil domain is divided into three segments that are separated by insertion loops.
      The C-terminal domain, which consists of 30 residues from each subunit, contains
      a beta-propeller-like structure with a hydrophobic interior. CONCLUSIONS: The
      residues within the C-terminal domain make extensive hydrophobic and some polar
      intersubunit interactions. This is consistent with the C-terminal domain being
      important for the correct assembly of fibritin, as shown earlier by mutational
      studies. Tight interactions between the C-terminal residues of adjacent subunits
      counteract the latent instability that is suggested by the structural properties
      of the coiled-coil segments. Trimerization is likely to begin with the formation
      of the C-terminal domain which subsequently initiates the assembly of the coiled
      coil. The interplay between the stabilizing effect of the C-terminal domain and
      the labile coiled-coil domain may be essential for the fibritin function and for
      the correct functioning of many other alpha-fibrous proteins.

PMID- 9261071
TI  - Steroid recognition and regulation of hormone action: crystal structure of
      testosterone and NADP+ bound to 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase.
AB  - BACKGROUND: Mammalian 3 alpha-hydroxysteroid dehydrogenases (3 alpha-HSDs)
      modulate the activities of steroid hormones by reversibly reducing their C3
      ketone groups. In steroid target tissues, 3 alpha-HSDs act on 5 alpha
      dihydrotestosterone, a potent male sex hormone (androgen) implicated in benign
      prostate hyperplasia and prostate cancer. Rat liver 3 alpha-HSD belongs to the
      aldo-keto reductase (AKR) superfamily and provides a model for mammalian 3 alpha
      , 17 beta- and 20 alpha-HSDs, which share > 65% sequence identity. The
      determination of the structure of 3 alpha-HSD in complex with NADP+ and
      testosterone (a competitive inhibitor) will help to further our understanding of
      steroid recognition and hormone regulation by mammalian HSDs. RESULTS: We have
      determined the 2.5 A resolution crystal structure of recombinant rat liver 3
      alpha-HSD complexed with NADP+ and testosterone. The structure provides the first
      picture of an HSD ternary complex in the AKR superfamily, and is the only
      structure to date of testosterone bound to a protein. It reveals that the C3
      ketone in testosterone, corresponding to the reactive group in a substrate, is
      poised above the nicotinamide ring which is involved in hydride transfer. In
      addition, the C3 ketone forms hydrogen bonds with two active-site residues
      implicated in catalysis (Tyr55 and His117). CONCLUSIONS: The active-site
      arrangement observed in the 3 alpha-HSD ternary complex structure suggests that
      each positional-specific and stereospecific reaction catalyzed by an HSD requires
      a particular substrate orientation, the general features of which can be
      predicted. 3 alpha-HSDs are likely to bind substrates in a similar manner to the
      way in which testosterone is bound in the ternary complex, that is with the A
      ring of the steroid substrate in the active site and the beta face towards the
      nicotinamide ring to facilitate hydride transfer. In contrast, we predict that 17
      beta-HSDs will bind substrates with the D ring of the steroid in the active site
      and with the alpha face towards the nicotinamide ring. The ability to bind
      substrates in only one or a few orientations could determine the positional
      specificity and stereospecificity of each HSD. Residues lining the steroid
      binding cavities are highly variable and may select these different orientations.

PMID- 9261072
TI  - Triosephosphate isomerase from Plasmodium falciparum: the crystal structure
      provides insights into antimalarial drug design.
AB  - BACKGROUND: Malaria caused by the parasite Plasmodium falciparum is a major
      public health concern. The parasite lacks a functional tricarboxylic acid cycle,
      making glycolysis its sole energy source. Although parasite enzymes have been
      considered as potential antimalarial drug targets, little is known about their
      structural biology. Here we report the crystal structure of triosephosphate
      isomerase (TIM) from P. falciparum at 2.2 A resolution. RESULTS: The crystal
      structure of P. falciparum TIM (PfTIM), expressed in Escherichia coli, was
      determined by the molecular replacement method using the structure of
      trypanosomal TIM as the starting model. Comparison of the PfTIM structure with
      other TIM structures, particularly human TIM, revealed several differences. In
      most TIMs the residue at position 183 is a glutamate but in PfTIM it is a
      leucine. This leucine residue is completely exposed and together with the
      surrounding positively charged patch, may be responsible for binding TIM to the
      erythrocyte membrane. Another interesting feature is the occurrence of a cysteine
      residue at the dimer interface of PfTIM (Cys13), in contrast to human TIM where
      this residue is a methionine. Finally, residue 96 of human TIM (Ser96), which
      occurs near the active site, has been replaced by phenylalanine in PfTIM.
      CONCLUSIONS: Although the human and Plasmodium enzymes share 42% amino acid
      sequence identity, several key differences suggest that PfTIM may turn out to be
      a potential drug target. We have identified a region which may be responsible for
      binding PfTIM to cytoskeletal elements or the band 3 protein of erythrocytes;
      attachment to the erythrocyte membrane may subsequently lead to the extracellular
      exposure of parts of the protein. This feature may be important in view of a
      recent report that patients suffering from P. falciparum malaria mount an
      antibody response to TIM leading to prolonged hemolysis. A second approach to
      drug design may be provided by the mutation of the largely conserved residue
      (Ser96) to phenylalanine in PfTIM. This difference may be of importance in
      designing specific active-site inhibitors against the enzyme. Finally, specific
      inhibition of PfTIM subunit assembly might be possible by targeting Cys13 at the
      dimer interface. The crystal structure of PfTIM provides a framework for new
      therapeutic leads.

PMID- 9261074
TI  - Out of the blue: the photocycle of the photoactive yellow protein.
AB  - A first real glance at the structural, spectral and temporal interplay that
      constitutes the photocycle of the photoactive yellow protein (PYP) has been
      obtained from a combination of time-resolved crystallography with mutational
      analysis and spectroscopic studies.

PMID- 9261073
TI  - The crystal structure of the nucleotide-free alpha 3 beta 3 subcomplex of F1
      ATPase from the thermophilic Bacillus PS3 is a symmetric trimer.
AB  - BACKGROUND: F1-ATPase, an oligomeric assembly with subunit stoichiometry alpha 3
      beta 3 gamma delta epsilon, is the catalytic component of the ATP synthase
      complex, which plays a central role in energy transduction in bacteria,
      chloroplasts and mitochondria. The crystal structure of bovine mitochondrial F1
      ATPase displays a marked asymmetry in the conformation and nucleotide content of
      the catalytic beta subunits. The alpha 3 beta 3 subcomplex of F1-ATPase has been
      assembled from subunits of the moderately thermophilic Bacillus PS3 made in
      Escherichia coli, and the subcomplex is active but does not show the catalytic
      cooperativity of intact F1-ATPase. The structure of this subcomplex should
      provide new information on the conformational variability of F1-ATPase and may
      provide insights into the unusual catalytic mechanism employed by this enzyme.
      RESULTS: The crystal structure of the nucleotide-free bacterial alpha 3 beta 3
      subcomplex of F1-ATPase, determined at 3.2 A resolution, shows that the oligomer
      has exact threefold symmetry. The bacterial beta subunits adopt a conformation
      essentially identical to that of the nucleotide-free beta subunit in
      mitochondrial F1-ATPase; the alpha subunits have similar conformations in both
      structures. CONCLUSIONS: The structures of the bacterial F1-ATPase alpha and beta
      subunits are very similar to their counterparts in the mitochondrial enzyme,
      suggesting a common catalytic mechanism. The study presented here allows an
      analysis of the different conformations adopted by the alpha and beta subunits
      and may ultimately further our understanding of this mechanism.

PMID- 9261075
TI  - The three-dimensional structure of a photosystem II core complex determined by
      electron crystallography.
AB  - BACKGROUND: Photosystem II (PSII) is a multisubunit protein complex which is
      embedded in the photosynthetic membranes of plants. It uses light energy to split
      water into molecular oxygen and reducing equivalents. PSII can be isolated with
      varying degrees of complexity in terms of its subunit composition and activity.
      To date, no three-dimensional (3-D) structure of the PSII complex has been
      determined which allows location of the proteins within the PSII complex and
      their orientation in relation to the thylakoid membrane. RESULTS: Two-dimensional
      (2-D) PSII core complex crystals composed of the two reaction centre proteins, D1
      and D2, two chlorophyll-binding proteins, CP47 and CP43, cytb559 and associated
      low molecular weight proteins were formed after reconstituting the isolated
      complex into purified thylakoid lipids. Electron micrographs of negatively
      stained crystals were used for 2-D and 3-D image analyses. In the resulting maps,
      the PSII complex is composed of two halves related by twofold rotational
      symmetry, thus, confirming the dimeric nature of the complex; each monomer
      appears to contain five domains. Comparison of the 3-D images with platinum
      shadowed images of the crystals allowed the likely lumenal and stromal surfaces
      of the complex to be identified and regions contained within the membrane to be
      inferred. The projection structure of 2-D crystals of a smaller CP47-D1-D2
      cytb559 complex was used to identify the domains apparently associated with CP43.
      CONCLUSION: The results indicate that PSII probably exists as a dimer in vivo.
      The extensive proteinaceous protrusions from the lumenal surface have been
      tentatively assigned to hydrophilic loops of CP47 and CP43; the positioning of
      these loops possibly implies their involvement in the water-splitting process.

PMID- 9261076
TI  - High-resolution icosahedral reconstruction: fulfilling the promise of cryo
      electron microscopy.
AB  - Two recent papers have defined the secondary structure of the hepatitis virus
      capsid using a combination of cryo-electron microscopy and icosahedral image
      reconstruction. These two papers do more than reveal a new fold for a virus
      protein; they herald a new era in which image reconstruction of single particles
      will provide reliable high-resolution structural information. In revealing the
      promise of these techniques to the structural biology community, their two papers
      should play a seminal role for single particle work, similar to that of the work
      of Unwin and Henderson on bacteriorhodopsin in revealing the potential of
      electron microscopy of membrane protein crystals. Indeed, the success of these
      single particle methods owes much to the development of high-resolution
      techniques for two-dimensional crystals. This review will summarize some of the
      history of icosahedral reconstruction from cryo-electron micrographs, compare the
      two different approaches used to obtain the recent results and outline some of
      the challenges and promises for the future.

PMID- 9261078
TI  - A cap for all occasions.
AB  - The 5' end of each polymerase II transcript is capped by a methylated guanosine
      triphosphate. The cap earmarks the mRNA for subsequent processing and
      nucleocytoplasmic transport, protects the mRNA from degradation and promotes
      efficient initiation of protein synthesis. The recently solved structures of
      capping enzymes and cap-protein complexes shed light on how the 5' ends of mRNAs
      are modified, and reveals the mechanisms by which the cap is recognized and how
      it functions in a diverse range of processes.

PMID- 9261079
TI  - Touring the landscapes: partially folded proteins examined by hydrogen exchange.
AB  - Recent studies on Escherichia coli ribonuclease H and several other proteins
      reveal a specific region in each protein that remains structured in partially
      folded conformations. These regions play a dominant role in determining the fold
      and stability of the protein.

PMID- 9261080
TI  - An atomic model of the outer layer of the bluetongue virus core derived from X
      ray crystallography and electron cryomicroscopy.
AB  - BACKGROUND: Bluetongue virus (BTV), which belongs to the Reoviridae family and
      orbivirus genus, is a non-enveloped, icosahedral, double-stranded RNA virus.
      Several protein layers enclose its genome; upon cell entry the outer layer is
      stripped away leaving a core, the surface of which is composed of VP7. The
      structure of the trimeric VP7 molecule has previously been determined using X-ray
      crystallography. The articulated VP7 subunit consists of two domains, one which
      is largely alpha-helical and the other, smaller domain, is a beta barrel with
      jelly-roll topology. The relative orientations of these two domains vary in
      different crystal forms. The structure of VP7 and the organizations of 780
      subunits of this molecule in the core of virus is central to the assembly and
      function of BTV. RESULTS: A 23 A resolution map of the core, determined using
      electron cryomicroscopy (cryoEM) data, reveals that the 260 trimers of VP7 are
      organized on a rather precise T = 13 laevo icosahedral lattice, in accordance
      with the theory of quasi-equivalence. The VP7 layer occupies a shell that is
      between 260 A and 345 A from the centre of the core. Below this radius (230-260
      A) lies the T = 1 layer of 120 molecules of VP3. By fitting the X-ray structure
      of an individual VP7 trimer onto the cryoEM BTV core structure, we have generated
      an atomic model of the VP7 layer of BTV. This demonstrates that one of the
      molecular structures seen in crystals of the isolated VP7 corresponds to the in
      vivo conformation of the molecule in the core. CONCLUSIONS: The beta-barrel
      domains of VP7 are external to the core and interact with protein in the outer
      layer of the mature virion. The lower, alpha-helical domains of VP7 interact with
      VP3 molecules which form the inner layer of the BTV core. Adjacent VP7 trimer
      trimer interactions in the T = 13 layer are mediated principally through well
      defined regions in the broader lower domains, to form a structure that conforms
      well with that expected from the theory of quasi-equivalence with no significant
      conformational changes within the individual trimers. The VP3 layer determines
      the particle size and forms a rather smooth surface upon which the two
      dimensional lattice of VP7 trimers is laid down.

PMID- 9261081
TI  - Structures of orbivirus VP7: implications for the role of this protein in the
      viral life cycle.
AB  - BACKGROUND: Bluetongue virus (BTV) is the prototypical virus of the genus
      orbivirus in the family Reoviridae and causes an economically important disease
      in domesticated animals, such as sheep. BTV is larger and more complex than any
      virus for which comprehensive atomic level structural information is available.
      Its capsid is made primarily from four structural proteins two of which, VP3 and
      VP7, form a core which remains intact as the virus penetrates the host cell. Each
      core particle contains 780 copies of VP7. The architecture of the trimeric VP7
      molecule has been revealed by crystallographic analysis and is unlike other viral
      coat proteins reported to date. RESULTS: Two new crystal structures of VP7 have
      been solved, one (a cleavage product) at close to atomic resolution and the other
      at lower resolution. The VP7 subunit consists of two domains. The smaller,
      'upper', domain is exposed on the core surface and has the beta jelly-roll motif
      common to many capsid proteins. The second, 'lower', domain is composed of a
      bundle of alpha helices. The cleavage product comprises the upper domain, which
      forms a rigid invariant trimeric fragment. The lower resolution structure of the
      intact molecule indicates that the alpha-helical domain can rotate about the
      linker to the upper domain to adopt radically different orientations with respect
      to the threefold axis in the intact protein. CONCLUSIONS: The crystal structures
      of VP7 reveal a remarkable mix of rigidity and flexibility that may provide
      insights towards understanding how VP7 interacts with the other capsid proteins
      of different stoichiometries. These results suggest that substantial
      conformational changes in VP7 occur at some stage in the viral life cycle. Such
      changes may be related to the central role that VP7 is likely to play in cell
      attachment and membrane penetration.

PMID- 9261082
TI  - Crystal structure of phosphoadenylyl sulphate (PAPS) reductase: a new family of
      adenine nucleotide alpha hydrolases.
AB  - BACKGROUND: Assimilatory sulphate reduction supplies prototrophic organisms with
      reduced sulphur for the biosynthesis of all sulphur-containing metabolites. This
      process is driven by a sequence of enzymatic steps involving phosphoadenylyl
      sulphate (PAPS) reductase. Thioredoxin is used as the electron donor for the
      reduction of PAPS to phospho-adenosine-phosphate (PAP) and sulphite. Unlike most
      electron-transfer reactions, there are no cofactors or prosthetic groups involved
      in this reduction and PAPS reductase is one of the rare examples of an enzyme
      that is able to store two electrons. Determination of the structure of PAPS
      reductase is the first step towards elucidating the biochemical details of the
      reduction of PAPS to sulphite. RESULTS: We have determined the crystal structure
      of PAPS reductase at 2.0 A resolution in the open, reduced form, in which a
      flexible loop covers the active site. The protein is active as a dimer, each
      monomer consisting of a central six-stranded beta sheet with alpha helices
      packing against each side. A highly modified version of the P loop, the
      fingerprint peptide of mononucleotide-binding proteins, is present in the active
      site of the protein, which appears to be a positively charged cleft containing a
      number of conserved arginine and lysine residues. Although PAPS reductase has no
      ATPase activity, it shows a striking similarity to the structure of the ATP
      pyrophosphatase (ATP PPase) domain of GMP synthetase, indicating that both enzyme
      families have evolved from a common ancestral nucleotide-binding fold.
      CONCLUSIONS: The sequence conservation between ATP sulphurylases, a subfamily of
      ATP PPases, and PAPS reductase and the similarities in both their mechanisms and
      folds, suggest an evolutionary link between the ATP PPases and PAPS reductases.
      Together with the N type ATP PPases, PAPS reductases and ATP sulphurylases are
      proposed to form a new family of homologous enzymes with adenine nucleotide alpha
      hydrolase activity. The open, reduced form of PAPS reductase is able to bind
      PAPS, whereas the closed oxidized form cannot. A movement between the two
      monomers of the dimer may allow this switch in conformation to occur.

PMID- 9261083
TI  - Crystal structures and inhibitor binding in the octameric flavoenzyme vanillyl
      alcohol oxidase: the shape of the active-site cavity controls substrate
      specificity.
AB  - BACKGROUND: Lignin degradation leads to the formation of a broad spectrum of
      aromatic molecules that can be used by various fungal micro-organisms as their
      sole source of carbon. When grown on phenolic compounds, Penicillium
      simplicissimum induces the strong impression of a flavin-containing vanillyl
      alcohol oxidase (VAO). The enzyme catalyses the oxidation of a vast array of
      substrates, ranging from aromatic amines to 4-alkyphenols. VAO is a member of a
      novel class of widely distributed oxidoreductases, which use flavin adenine
      dinucleotide (FAD) as a cofactor covalently bound to the protein. We have carried
      out the determination of the structure of VAO in order to shed light on the most
      interesting features of these novel oxidoreductases, such as the functional
      significance of covalent flavinylation and the mechanism of catalysis. RESULTS:
      The crystal structure of VAO has been determined in the native state and in
      complexes with four inhibitors. The enzyme is an octamer with 42 symmetry; the
      inhibitors bind in a hydrophobic, elongated cavity on the si side of the flavin
      molecule. Three residues, Tyr108, Tyr503 and Arg504 form an anion-binding
      subsite, which stabilises the phenolate form of the substrate. The structure of
      VAO complexed with the inhibitor 4-(1-heptenyl)phenol shows that the catalytic
      cavity is completely filled by the inhibitor, explaining why alkylphenols bearing
      aliphatic substituents longer than seven carbon atoms do not bind to the enzyme.
      CONCLUSIONS: The shape of the active-site cavity controls substrate specificity
      by providing a 'size exclusion mechanism'. Inside the cavity, the substrate
      aromatic ring is positioned at an angle of 18 degrees to the flavin ring. This
      arrangement is ideally suited for a hydride transfer reaction, which is further
      facilitated by substrate deprotonation. Burying the substrate beneath the protein
      surface is a recurrent strategy, common to many flavoenzymes that effect
      substrate oxidation or reduction via hydride transfer.

PMID- 9261084
TI  - A binary complex of the catalytic subunit of cAMP-dependent protein kinase and
      adenosine further defines conformational flexibility.
AB  - BACKGROUND: cAMP-dependent protein kinase (cAPK), a ubiquitous protein in
      eukaryotic cells, is one of the simplest members of the protein kinase family. It
      was the first protein kinase to be crystallized and continues to serve as a
      biochemical and structural prototype for this family of enzymes. To further
      understand the conformational changes that occur in different liganded and
      unliganded states of cAPK, the catalytic subunit of cAPK was crystallized in the
      absence of peptide inhibitor. RESULTS: The crystal structure of the catalytic
      subunit of mouse recombinant cAPK (rC) complexed with adenosine was solved at 2.6
      A resolution and refined to a crystallographic R factor of 21.9% with good
      stereochemical parameters. This is the first structure of the rC subunit that
      lacks a bound inhibitor or substrate peptide. The structure was solved by
      molecular replacement and comprises two lobes (large and small) which contain a
      number of conserved loops. CONCLUSIONS: The binary complex of rC and adenosine
      adopts an 'intermediate' conformation relative to the previously described
      'closed' and 'open' conformations of other rC complexes. Based on a comparison of
      these structures, the induced fit that is necessary for catalysis and closing of
      the active-site cleft appears to be confined to the small lobe, as in the absence
      of the peptide the conformation of the large lobe, including the peptide-docking
      surface, does not change. Three specific components contribute to the closing of
      the cleft: rotation of the small lobe; movement of the C-terminal tail; and
      closing of the so-called glycine-rich loop. There is no induced fit in the large
      lobe to accommodate the peptide and the closing of the cleft. A portion of the C
      terminal tail, residues 315-334, serves as a gate for the entry or exit of the
      nucleotide into the hydrophobic active-site cleft.

PMID- 9261085
TI  - Examining the conformational dynamics of macromolecules with time-resolved
      synchrotron X-ray 'footprinting'.

PMID- 9261086
TI  - Antibody fragment Fv4155 bound to two closely related steroid hormones: the
      structural basis of fine specificity.
AB  - BACKGROUND: The concentration of steroid glucuronides in serial samples of early
      morning urine (EMU) can be used to predict the fertile period in the female
      menstrual cycle. The monoclonal antibody 4155 has been used as a convenient means
      of measuring the concentration of steroid glucuronides in EMU, as it specifically
      recognises the steroid hormone estrone beta-D-glucuronide (E3G), with very high
      affinity, and the closely related hormone estriol 3-(beta-d-glucuronide) (EI3G),
      with reduced affinity. Although 4115 binds these hormones with different
      affinities, EI3G differs from E3G only in the addition of a hydroxyl group and
      reduction of an adjacent carbonyl. To investigate the structural basis of this
      fine binding specificity, we have determined the crystal structures of the
      variable fragment (Fv) of 4155 in complex with each of these hormones. RESULTS:
      Two crystal forms of the Fv4155-EI3G complex, at resolutions of 2.1 A and 2.5 A,
      and one form of the Fv4155-E3G complex, at 2.1 A resolution were solved and
      refined. The crystal structures show the E3G or EI3G antigen lying in an extended
      cleft, running form the centre of the antibody combining site down one side of
      the variable domain interface, and formed almost entirely from residues in the
      heavy chain. The binding cleft lies primarily between the heavy chain
      complementarity determining regions (CDRs), rather than in the interface between
      the heavy and light chains. In both complexes the binding of the glucuronic
      sugar, and rings A and B of the steroid, is specified by the shape of the narrow
      cleft. Analysis of the Fv structure reveals that five of the six CDR regions can
      be assigned to one of the predefined canonical structural classes. CONCLUSIONS:
      The difference in the binding affinity of Fv4155 for the two steroid hormones is
      accounted for by a subtle combination of a less favoured hydrogen-bond geometry,
      and a minor rearrangement of the water molecule network around the binding site.
      The rearrangement of water molecules results from the burial of the additional
      hydroxyl group of the EI3G in a hydrophobic environment.

PMID- 9261087
TI  - Structure of poliovirus type 2 Lansing complexed with antiviral agent SCH48973:
      comparison of the structural and biological properties of three poliovirus
      serotypes.
AB  - BACKGROUND: Polioviruses are human pathogens and the causative agents of
      poliomyelitis. Polioviruses are icosahedral single-stranded RNA viruses, which
      belong to the picornavirus family, and occur as three distinct serotypes. All
      three serotypes of poliovirus can infect primates, but only type 2 can infect
      mice. The crystal structures of a type 1 and a type 3 poliovirus are already
      known. Structural studies of poliovirus type 2 Lansing (PV2L) were initiated to
      try to enhance our understanding of the differences in host range specificity,
      antigenicity and receptor binding among the three serotypes of poliovirus.
      RESULTS: The crystal structure of the mouse neurovirulent PV2L complexed with a
      potent antiviral agent, SCH48973, was determined at 2.9 A resolution. Structural
      differences among the three poliovirus serotypes occur primarily in the loop
      regions of the viral coat proteins (VPs), most notably in the loops of VP1 that
      cluster near the fivefold axes of the capsid, where the BC loop of PV2L is
      disordered. Unlike other known structures of enteroviruses, the entire
      polypeptide chain of PV2L VP4 is visible in the electron density and RNA bases
      are observed stacking with conserved aromatic residues (Tyr4020 and Phe4046) of
      VP4. The broad-spectrum antiviral agent SCH48973 is observed binding in a pocket
      within the beta-barrel of VP1, in approximately the same location that natural
      'pocket factors' bind to polioviruses. SCH48973 forms predominantly hydrophobic
      interactions with the pocket residues. CONCLUSIONS: Some of the conformational
      changes required for infectivity and involved in the control of capsid stability
      and neurovirulence in mice may occur in the vicinity of the fivefold axis of the
      poliovirus, where there are significant structural differences among the three
      poliovirus serotypes in the surface exposed loops of VP1 (BC, DE, and HI). A
      surface depression is located at the fivefold axis of PV2L that is not present in
      the other two poliovirus serotypes. The observed interaction of RNA with VP4
      supports the observation that loss of VP4 ultimately leads to the loss of viral
      RNA. A model is proposed that suggests dual involvement of the virion fivefold
      and pseudo-threefold axes in receptor-mediated initiation of infection by
      picornaviruses.

PMID- 9261088
TI  - Backbone dynamics of homologous fibronectin type III cell adhesion domains from
      fibronectin and tenascin.
AB  - BACKGROUND: Fibronectin type III domains are found as autonomously-folded domains
      in a large variety of multidomain proteins, including extracellular matrix
      proteins. A subset of these domains employ an Arg-Gly-Asp (RGD) tripeptide motif
      to mediate contact with cell-surface receptors (integrins). This motif mediates
      protein-protein interactions in a diverse range of biological processes, such as
      in tissue development, would healing and metastasis. The molecular basis for
      affinity and specificity of cell adhesion via type III domains has not been
      clearly established. The tenth type III domain from fibronectin (FNfn10) and the
      third type III domain from tenascin-C (TNfn3) have 27% sequence identity and
      share the same overall protein fold, but present the RGD motifs in different
      structural contexts. The dynamical properties of the RGD motifs may affect the
      specificity and affinity of the FNfn10 and TNfn3 domains. Structure-dynamics
      correlations for these structurally homologous proteins may reveal common
      molecular features which are important to the dynamical properties of proteins.
      RESULTS: The intramolecular dynamics of the protein backbones of FNfn10 and TNfn3
      have been studied by 15N nuclear spin relaxation. The FG loop in FNfn10, which
      contains the RGD motif, exhibits extensive flexibility on picosecond to
      nanosecond timescales, but motions on microsecond to millisecond timescales are
      not observed. The equivalent region in TNfn3 is as rigid as regular elements of
      secondary structure. The CC' loop also is more flexible on picosecond-nanosecond
      timescales in FNfn10 than in TNfn3. Conformational exchange, reflecting
      flexibility on microsecond-millisecond timescales, is observed in beta strands A
      and B of both FNfn10 and TNfn3. CONCLUSIONS: Comparison of the structures of the
      FNfn10 and TNfn3 reveals several features related to their different dynamical
      properties. The larger amplitude motions of loops in FNfn10 are consistent with
      the hypothesis that flexibility of these regions facilitates induced-fit
      recognition of fibronectin by multiple receptors. Similarly, the more rigid loops
      of TNfn3 may reflect greater specificity for particular integrins. The
      correlations observed between structural features and dynamical properties of the
      homologous type III domains indicate the influence of hydrogen bonding and
      hydrophobic packing on dynamical fluctuations in proteins.

PMID- 9261091
TI  - Low density lipoprotein oxidation and its pathobiological significance.

PMID- 9261092
TI  - Cyclic ADP-ribose enhances coupling between voltage-gated Ca2+ entry and
      intracellular Ca2+ release.
AB  - Ca2+ release from intracellular stores can be activated in neurons by influx of
      Ca2+ through voltage-gated Ca2+ channels. This process, called Ca2+-induced Ca2+
      release, relies on the properties of the ryanodine receptor and represents a
      mechanism by which Ca2+ influx during neuronal activity can be amplified into
      large intracellular Ca2+ signals. In a differentiated neuroblastoma cell line, we
      show that caffeine, a pharmacological activator of the ryanodine receptor,
      released Ca2+ from intracellular stores in a Ca2+-dependent and ryanodine
      sensitive manner. The pyridine nucleotide, cyclic ADP-ribose, thought to be an
      endogenous modulator of ryanodine receptors also amplified Ca2+-induced Ca2+
      release in these neurons. Cyclic ADP-ribose enhanced the total cytoplasmic Ca2+
      levels during controlled Ca2+ influx through voltage gated channels, in a
      concentration-dependent and ryanodine-sensitive manner and also increased the
      sensitivity with which a small amount of Ca2+ influx could trigger additional
      release from the ryanodine-sensitive intracellular Ca2+ stores. Single cell
      imaging showed that following the Ca2+ influx, cyclic ADP-ribose enhanced the
      spatial spread of the Ca2+ signal from the edge of the cell into its center.
      These powerful actions suggest a role for cyclic ADP-ribose in the functional
      coupling of neuronal depolarization, Ca2+ entry, and global intracellular Ca2+
      signaling.

PMID- 9261094
TI  - Molecular cloning of a non-inactivating proton-gated Na+ channel specific for
      sensory neurons.
AB  - We have cloned and expressed a novel proton-gated Na+ channel subunit that is
      specific for sensory neurons. In COS cells, it forms a Na+ channel that responds
      to a drop of the extracellular pH with both a rapidly inactivating and a
      sustained Na+ current. This biphasic kinetic closely resembles that of the H+
      gated current described in sensory neurons of dorsal root ganglia (1). Both the
      abundance of this novel H+-gated Na+ channel subunit in sensory neurons and the
      kinetics of the channel suggest that it is part of the channel complex
      responsible for the sustained H+-activated cation current in sensory neurons that
      is thought to be important for the prolonged perception of pain that accompanies
      tissue acidosis (1, 2).

PMID- 9261093
TI  - A unique domain of pRb2/p130 acts as an inhibitor of Cdk2 kinase activity.
AB  - The Cdk2 kinase has long been known to be involved in the progression of
      mammalian cells past the G1 phase restriction point and through DNA replication
      in the cell cycle. The Rb family of proteins, consisting of pRb, p107, and
      pRb2/p130, has also been shown to monitor progression of G1 phase, mostly through
      their interaction with E2F family members. p107 is able to inhibit Cdk2 kinase
      activity through this interaction via a p21-related domain present in the C
      terminus of the protein. We show here that pRb2/p130 also possesses this
      activity, but through a separate domain. Moreover, we correlate the increased
      expression of pRb2/p130 during various cellular processes with the decreased
      kinase activity of Cdk2. We hypothesize that pRb2/p130 may act not only to bind
      and modify E2F activity, but also to inhibit Cdk2 kinase activity in concert with
      p21 in a manner different from p107.

PMID- 9261095
TI  - Characterization of the interactions between PDZ domains of the protein-tyrosine
      phosphatase PTPL1 and the carboxyl-terminal tail of Fas.
AB  - The intracellular protein-tyrosine phosphatase PTPL1 has five PDZ domains and one
      of them, PDZ 2, has previously been shown to interact with the C-terminal tail of
      Fas, a member of the tumor necrosis factor receptor family. Using a peptide
      binding assay, we show that not only PDZ 2 but also PDZ 4 of PTPL1 interacts with
      high affinity with peptides derived from the C terminus of Fas. The five most C
      terminal amino acid residues of Fas influence the affinity of the interaction.
      Whereas the glutamine and isoleucine residues in the 4th and 5th positions from
      the C terminus affect the interaction in a negative and positive manner,
      respectively, the three C-terminal amino acid residues (SLV) are necessary and
      sufficient for a high affinity interaction to occur. Both the carboxyl group and
      side chain of the valine residue at the C terminus of Fas are essential, and the
      leucine and serine residues in the 2nd and 3rd positions, respectively, from the
      C terminus are important for the interactions with PDZ 2 and PDZ 4 of PTPL1.

PMID- 9261097
TI  - Drug-stimulated ATPase activity of human P-glycoprotein requires movement between
      transmembrane segments 6 and 12.
AB  - Transmembrane segments (TM) 6 and 12 are directly connected to the ATP-binding
      domain in each homologous half of P-glycoprotein and are postulated to be
      important for drug-protein interactions. Cysteines introduced into TM6 (L332C,
      F343C, G346C, and P350C) were oxidatively cross-linked to cysteines introduced
      into TM12 (L975C, M986C, G989C, and S993C, respectively). The pattern of cross
      linking was consistent with a left-handed coiled coil arrangement of the two
      helices. To detect conformational changes between the helices during drug
      stimulated ATPase activity, we tested the effects of substrates and ATP on cross
      linking. Cyclosporin A, verapamil, vinblastine, and colchicine inhibited cross
      linking of mutants F343C/M986C, G346C/G989C, and P350C/S993C. By contrast, ATP
      promoted cross-linking between only L332C/L975C. Enhanced cross-linking between
      L332C/L975C was due to ATP hydrolysis, since cross-linked product was not
      observed in the presence of ATP and vanadate, ADP, ADP and vanadate, or AMP-PNP.
      Cross-linking between P350C/S993C inhibited verapamil-stimulated ATPase activity
      by about 75%. Drug-stimulated ATPase activity, however, was fully restored in the
      presence of dithiothreitol. These results show that TM6 and TM12 undergo
      different conformational changes upon drug binding or during ATP hydrolysis, and
      that movement between these two helices is essential for drug-stimulated ATPase
      activity.

PMID- 9261096
TI  - Scavenger receptor BI promotes high density lipoprotein-mediated cellular
      cholesterol efflux.
AB  - Scavenger receptor BI (SR-BI) binds high density lipoproteins (HDL) with high
      affinity and mediates the selective uptake of HDL cholesteryl ester. We examined
      the potential role of SR-BI in mediating cellular cholesterol efflux. In Chinese
      hamster ovary cells stably transfected with murine SR-BI, overexpression of SR-BI
      resulted in a 3-4-fold stimulation of initial cholesterol efflux rates. Efflux
      rates correlated with SR-BI expression in cells and HDL concentration in the
      medium. When incubated with synthetic cholesterol-free HDL, SR-BI-transfected
      cells showed approximately 3-fold increases in initial rates of efflux compared
      with control cells, indicating that SR-BI expression enhances net cholesterol
      efflux mediated by discoidal HDL. In six different cell types, including cultured
      macrophages, the rate of efflux of cholesterol mediated by HDL or serum was well
      correlated with cellular SR-BI expression level. In addition, in situ
      hybridization experiments revealed that SR-BI mRNA was expressed in the thickened
      intima of atheromatous aorta of apolipoprotein E knockout mice. Thus, SR-BI is an
      authentic HDL receptor mediating cellular cholesterol efflux. SR-BI may
      facilitate the initial steps of HDL-mediated cholesterol efflux in the arterial
      wall as well as later steps of reverse cholesterol transport involving uptake of
      HDL cholesterol in the liver.

PMID- 9261098
TI  - 14-3-3 zeta negatively regulates raf-1 activity by interactions with the Raf-1
      cysteine-rich domain.
AB  - Although Raf-1 is a critical effector of Ras signaling and transformation, the
      mechanism by which Ras promotes Raf-1 activation is complex and remains poorly
      understood. We recently reported that Ras interaction with the Raf-1 cysteine
      rich domain (Raf-CRD, residues 139-184) may be required for Raf-1 activation. The
      Raf-CRD is located in the NH2-terminal negative regulatory domain of Raf-1 and is
      highly homologous to cysteine-rich domains found in protein kinase C family
      members. Recent studies indicate that the structural integrity of the Raf-CRD is
      also critical for Raf-1 interaction with 14-3-3 proteins. However, whether 14-3-3
      proteins interact directly with the Raf-CRD and how this interaction may mediate
      Raf-1 function has not been determined. In the present study, we demonstrate that
      14-3-3 zeta binds directly to the isolated Raf-CRD. Moreover, mutation of Raf-1
      residues 143-145 impairs binding of 14-3-3, but not Ras, to the Raf-CRD.
      Introduction of mutations that impair 14-3-3 binding resulted in full-length Raf
      1 mutants with enhanced transforming activity. Thus, 14-3-3 interaction with the
      Raf-CRD may serve in negative regulation of Raf-1 function by facilitating
      dissociation of 14-3-3 from the NH2 terminus of Raf-1 to promote subsequent
      events necessary for full activation of Raf-1.

PMID- 9261100
TI  - Salicylic acid is a reducing substrate and not an effective inhibitor of
      ascorbate peroxidase.
AB  - This communication describes the interactions of salicylic acid (SA) with plant
      ascorbate peroxidase (APX). Contrary to a recent report (Durner, J., and Klessig,
      D. F. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 11312-11316) we show
      conclusively that ascorbate oxidation by APX is not inhibited by SA (10 mM), but
      that SA is a slow reducing substrate of this enzyme. The suggestion that SA
      dependent inhibition of APX in planta may result in the elevation of H2O2 levels,
      which in turn acts as a second messenger in systemic acquired resistance
      signaling, is therefore not tenable. We conclude that APX remains a key
      antioxidant during systemic acquired resistance following pathogenic infection of
      plants. The transient products of SA oxidation by APX appear to be SA free
      radicals that undergo subsequent chemistry. APX-dependent oxidation of SA could
      be essential for diminishing the detrimental effects of this phenolic acid on
      plant cells.

PMID- 9261099
TI  - Complex regulation of the BRCA1 gene.
AB  - We have analyzed the promoter region of the human BRCA1 gene in detail and
      demonstrate that the expression of the BRCA1 gene is under complex regulation.
      First, its transcription is under the control of two promoters generating two
      distinct transcripts alpha and beta, and second, promoter alpha is shared with
      the adjacent NBR2 gene and is bi-directional. Both promoter alpha and promoter
      beta are responsive to estrogen stimulation. We also discerned that there are
      striking differences in both the genomic organization and immediate cis-control
      elements of the BRCA1 gene between humans and mice.

PMID- 9261101
TI  - Stimulation of cyclic ADP-ribose synthesis by acetylcholine and its role in
      catecholamine release in bovine adrenal chromaffin cells.
AB  - Cyclic ADP-ribose (cADPR) is suggested to be a novel messenger of ryanodine
      receptors in various cellular systems. However, the regulation of its synthesis
      in response to cell stimulation and its functional roles are still unclear. We
      examined the physiological relevance of cADPR to the messenger role in
      stimulation-secretion coupling in cultured bovine adrenal chromaffin cells.
      Sensitization of Ca2+-induced Ca2+ release (CICR) and stimulation of
      catecholamine release by cADPR in permeabilized cells were demonstrated along
      with the contribution of CICR to intracellular Ca2+ dynamics and secretory
      response during stimulation of intact chromaffin cells. ADP-ribosyl cyclase was
      activated in the membrane preparation from chromaffin cells stimulated with
      acetylcholine (ACh), excess KCl depolarization, and 8-bromo-cyclic-AMP. ACh
      induced activation of ADP-ribosyl cyclase was dependent on the influx of Ca2+
      into cells and on the activation of cyclic AMP-dependent protein kinase. These
      and previous findings that ACh activates adenylate cyclase by Ca2+ influx in
      chromaffin cells suggested that ACh induces activation of ADP-ribosyl cyclase
      through Ca2+ influx and cyclic AMP-mediated pathways. These results provide
      evidence that the synthesis of cADPR is regulated by cell stimulation, and the
      cADPR/CICR pathway forms a significant signal transduction for secretion.

PMID- 9261102
TI  - Activation of caspase-2 in apoptosis.
AB  - Members of the CED-3/interleukin-1beta-converting enzyme (ICE) protease (caspase)
      family are synthesized as proforms, which are proteolytically cleaved and
      activated during apoptosis. We report here that caspase-2 (ICH-1/NEDD-2), a
      member of the ICE family, is activated during apoptosis by another ICE member, a
      caspase-3 (CPP32)-like protease(s). When cells are induced to undergo apoptosis,
      endogenous caspase-2 is first cleaved into three fragments of 32-33 kDa and 14
      kDa, which are then further processed into 18- and 12-kDa active subunits. Up to
      50 microM N-acetyl-Asp-Glu-Val-Asp-aldehyde (DEVD-CHO), a caspase-3-preferred
      peptide inhibitor, inhibits caspase-2 activation and DNA fragmentation in vivo,
      but does not prevent loss of mitochondrial function, while higher concentrations
      of DEVD-CHO (>50 microM) inhibit both. In comparison, although the activity of
      caspase-3 is very sensitive to the inhibition of DEVD-CHO (<50 nM), inhibition of
      caspase-3 activation as marked by processing of the proform requires more than
      100 microM DEVD-CHO. Our results suggest that the first cleavage of caspase-2 is
      accomplished by a caspase-3-like activity, and other ICE-like proteases less
      sensitive to DEVD-CHO may be responsible for activation of caspase-3 and loss of
      mitochondrial function.

PMID- 9261103
TI  - Consequences of seven novel mutations on the expression and structure of
      keratinocyte transglutaminase.
AB  - We report the molecular characterization of seven new keratinocyte
      transglutaminase mutations (R315C, S358R, V379L, G473S, R687C, deletion Delta679
      696, R127Stop) found in lamellar ichthyosis patients. Arg-315, Ser-358, Val-379,
      and Gly-473 are highly conserved residues in transglutaminases while Arg-687 and
      Delta679-696 are not. All mutations strongly decreased transglutaminase activity
      and protein levels. The mutation R127Stop diminished the amount of mRNA.
      Structural analysis of these mutations based on the factor XIII A-subunit crystal
      structure demonstrated that Arg-315, Ser-358, Val-379, and Gly-473 are located in
      the catalytic core domain, and Arg-687 and the deletion are in the beta-barrel
      domains. The side chains of amino acids Arg-315, Ser-358, and Gly-473 make ionic
      and hydrogen bonds important for folding and structural stability of the enzyme
      but are not directly involved in catalysis. Val-379 is two amino acids away from
      the active site cysteine, and its change into leucine disturbs the active site
      structure. The decreased activity and protein level after expression of the R687C
      and Delta679-696 TGK cDNA in TGK negative keratinocytes excluded that they are
      polymorphisms. These results identify important amino acids in the central core
      domain of transglutaminases and show that the C-terminal end influences the
      structural and functional integrity of TGK.

PMID- 9261104
TI  - Synthetic rat V1a vasopressin receptor fragments interfere with vasopressin
      binding via specific interaction with the receptor.
AB  - To study the vasopressin receptor domains involved in the hormonal binding, we
      synthesized natural and modified fragments of V1a vasopressin receptor and tested
      their abilities to affect hormone-receptor interactions. Natural fragments
      mimicking the external loops one, two, and three were able to inhibit specific
      vasopressin binding to V1a receptor. In contrast, the natural N-terminal part of
      the V1a vasopressin receptor was found inactive. One fragment, derived from the
      external second loop and containing an additional C-terminal cysteine amide, was
      able to fully inhibit the specific binding of both labeled vasopressin agonist
      and antagonist to rat liver V1a vasopressin receptor and the vasopressin
      sensitive phospholipase C of WRK1 cells. The peptide-mediated inhibition involved
      specific interactions between the V1a receptor and synthetic V1a vasopressin
      receptor fragment since 1) it was dependent upon the vasopressin receptor subtype
      tested (Ki(app) for the peptide: 3.7, 14.6, and 64.5 microM for displacing
      [3H]vasopressin from rat V1a, V1b, and V2 receptors, respectively; 2) it was
      specific and did not affect sarcosin 1-angiotensin II binding to rat liver
      membranes; 3) it was not mimicked by vasopressin receptor unrelated peptides
      exhibiting putative detergent properties; and 4) no direct interaction between
      [3H]vasopressin and synthetic peptide linked to an affinity chromatography column
      could be observed. Such an inhibition affected both the maximal binding capacity
      of the V1a vasopressin receptor and its affinity for the labeled hormone,
      depending upon the dose of synthetic peptide used and was partially irreversible.
      Structure-activity studies using a serie of synthetic fragments revealed the
      importance of their size and cysteinyl composition. These data indicate that some
      peptides mimicking extracellular loops of the V1a vasopressin receptor may
      interact with the vasopressin receptor itself and modify its coupling with
      phospholipase C.

PMID- 9261105
TI  - Soluble amyloid Abeta-(1-40) exists as a stable dimer at low concentrations.
AB  - Recent studies have implicated the amyloid Abeta peptide and its ability to self
      assemble as key factors in the pathogenesis of Alzheimer's disease. Relatively
      little is known about the structure of soluble Abeta or its oligomeric state, and
      the existing data are often contradictory. In this study, we used intrinsic
      fluorescence of wild type Abeta-(1-40), fluorescence resonance energy transfer
      (FRET), and gel filtration chromatography to examine the structure of Abeta-(1
      40) in solution. We synthesized a series of mono-substituted fluorescent Abeta-(1
      40) derivatives to use as donors and acceptors in FRET experiments. We selected
      fluorescent peptides that exhibit aggregation properties comparable to wild type
      Abeta for analysis in donor-acceptor pairs; two labeled with 5-(2
      ((iodoacetyl)amino)ethyl)aminonaphthylene-1-sulfonic acid at Cys-25 or Cys-34 and
      fluorescein maleimide at Cys-4 or Cys-7. Another peptide containing a Trp
      substitution at position 10 was used as an acceptor for the intrinsic Tyr
      fluorescence of wild type Abeta-(1-40). Equilibrium studies of the denaturation
      of Abeta-(1-40) by increasing concentrations of dimethyl sulfoxide (Me2SO) were
      conducted by monitoring fluorescence, with a midpoint value for the unfolding
      transition of both the substituted and wild type peptides at among 40 and 50%
      Me2SO. Abeta-(1-40) is well solvated and largely monomeric in Me2SO as evidenced
      by a lack of FRET. When donor and acceptor Abeta derivatives are mixed together
      in Me2SO and then diluted 10-fold into aqueous Tris-HCl buffer at pH 7.4,
      efficient FRET is observed immediately for all pairs of fluorescent peptides,
      indicating that donor-acceptor dimers exist in solution. FRET is abolished by the
      addition of an excess of unlabeled Abeta-(1-40), demonstrating that the
      fluorescent peptides interact with wild type Abeta-(1-40) to form heterodimers
      that do not exhibit FRET. The Abeta-(1-40) dimers appear to be very stable,
      because no subunit exchange is observed after 24 h between fluorescent
      homodimers. Gel filtration confirms that nanomolar concentrations of 14C-labeled
      Abeta-(1-40) and fluorescein-labeled Abeta-(1-40) elute at the same dimeric
      position as wild type Abeta-(1-40), suggesting that soluble Abeta-(1-40) is also
      dimeric at more physiologically plausible concentrations.

PMID- 9261106
TI  - A type I interferon signaling factor, ISF21, encoded on chromosome 21 is distinct
      from receptor components and their down-regulation and Is necessary for
      transcriptional activation of interferon-regulated genes.
AB  - The type I interferons (IFNs) are a family of cytokines, comprising at least 17
      subtypes, which exert pleiotropic actions by interaction with a multi-component
      cell surface receptor and at least one well characterized signal transduction
      pathway involving JAK/STAT (Janus kinase/signal transducer and activator of
      transcription) proteins. In a previous report, we showed that a signaling factor,
      encoded by a gene located on the distal portion of chromosome 21, distinct from
      the IFNAR-1 receptor, was necessary for 2'-5'-oligoadenylate synthetase activity
      and antiviral responses, but not for high affinity ligand binding. In the present
      studies using hybrid Chinese hamster ovary cell lines containing portions of
      human chromosome 21, we show that the type I IFN signaling molecule, designated
      herein as ISF21, is distinct from the second receptor component, IFNAR-2, which
      is expressed in signaling and non-signaling cell lines. The location of the gene
      encoding ISF21 is narrowed to a region between the 10;21 and the r21 breakpoints,
      importantly eliminating the Mx gene located at 21q22.3 (the product of which is
      involved in IFN-induced antiviral responses) as a candidate for the signaling
      factor. To characterize the action of this factor in the type I IFN signaling
      pathway, we show that it acts independently of receptor down-regulation following
      ligand binding, both of which occur equally in the presence or absence of the
      factor. In addition, we demonstrate that ISF21 is necessary for transcriptional
      activation of 2'-5'-oligoadenylate synthetase, 6-16, and guanylate-binding
      protein gene promoter reporter constructs, which are mediated by several
      signaling pathways. ISF21 represents a novel factor as the localization to
      chromosome 21, and the data presented in this study exclude any of the known type
      I IFN signal-transducing molecules.

PMID- 9261107
TI  - Site-directed mutagenesis of either the highly conserved Trp-22 or the moderately
      conserved Trp-95 to a large, hydrophobic residue reduces the thermodynamic
      stability of a spectrin repeating unit.
AB  - As reported previously (MacDonald, R. I., Musacchio, A., Holmgren, R. A., and
      Saraste, M. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 1299-1303), an unfolded
      peptide was obtained by site-directed mutagenesis of Trp-22 to Ala in the cloned,
      wild type 17th repeating unit (alpha17) of chicken brain alpha-spectrin. Trp
      occurs in position 22 of nearly all repeating units of spectrin. In the present
      study, Trp-22 was mutated to Phe or to Tyr to compare thermodynamic stabilities
      of urea-induced unfolding of alpha16 and mutants thereof. alpha16 was chosen for
      this study instead of alpha17, because alpha16 has two tryptophans, allowing urea
      induced unfolding to be tracked by the fluorescence of the Trp remaining in each
      mutant peptide and by circular dichroism in the far UV. The free energies of
      unfolding of W22Y and W22F were 50% that of alpha16, showing that Trp-22 is
      crucial in stabilizing the triple helical bundle motif of the spectrin repeating
      unit. Mutation of the moderately conserved Trp-95 of alpha16 to Val, which
      occupies position 95 in alpha17, also yielded a peptide with 50% of the free
      energy of unfolding of alpha16. Thus, the thermodynamic stability of a given
      spectrin repeating unit may depend on both moderately and highly conserved
      tryptophans. Different structural roles of Trp-22 and Trp-95 in alpha16 are
      suggested by the slightly higher wavelength of maximum emission of Trp-22, the
      greater acrylamide quenching of Trp-95 than Trp-22, and the longer lifetime of
      Trp-95. For comparison with alpha16, urea-induced unfolding of spectrin dimer
      isolated from human red cells was monitored by far UV-CD and by tryptophan
      fluorescence. Thermodynamic parameters could not be rigorously derived for the
      stability of spectrin dimer because unfolding of spectrin dimer involved more
      than two states, unlike unfolding of cloned repeating units. However, the similar
      midpoints of CD-monitored denaturation curves of alpha16 and spectrin dimer, i.
      e. 2.7 and 3.2 M urea, respectively, indicate that investigation of cloned
      repeating units of spectrin can provide physiologically relevant information on
      these structures.

PMID- 9261108
TI  - Production of a specific major histocompatibility complex class I-restricted
      epitope by ubiquitin-dependent degradation of modified ovalbumin in lymphocyte
      lysate.
AB  - Peptide epitopes presented through class I major histocompatability complex (MHC
      class I) on the cell surface, are generated by proteolytic processing of protein
      antigens in the cytoplasm. The length and amino acid sequence determine whether a
      given peptide can fit into the peptide binding groove of class I heavy chain
      molecules and subsequently be presented to the immune system. The mode of action
      of the processing pathway is therefore of great interest. To study the processing
      mechanism of MHC class I-restricted intracellular antigens, we reconstituted the
      proteolytic processing of a model antigen in a cell-free system. Incubation of
      oxidized and urea-treated OVA in lymphocyte lysate resulted in partial
      degradation of the antigen. Degradation of the antigen depended on the presence
      of ATP. Addition of methylated ubiquitin abolished the reaction which was then
      restored by addition of an excess of native ubiquitin, indicating that the
      breakdown of the antigen in lymphocyte lysate is mediated by the ubiquitin
      proteolytic system. Upon incubation of modified OVA in lymphocyte lysate, a
      specific antigenic peptide was generated. The peptide was recognized by cytotoxic
      T lymphocytes directed against OVA-derived, H-2Kb-restricted peptide (SIINFEKL),
      and by a monoclonal antibody that recognizes cell-bound Kb-SIINFEKL complexes.
      Formation of the peptide epitope depended on the presence of ATP and ubiquitin.
      These results indicate that proteolytic processing of modified OVA is carried out
      by the ubiquitin-mediated degradation system. The experimental system described
      provides a tool to analyze the molecular mechanisms underlying the generation of
      specific, MHC class I-restricted peptide epitopes.

PMID- 9261109
TI  - Activation of type IV procollagenases by human tumor-associated trypsin-2.
AB  - Increased production of proteinases, such as matrix metalloproteinases (MMPs), is
      a characteristic feature of malignant tumors. Some human cancers and cell lines
      derived from them also express trypsinogen, but the function of the
      extrapancreatic trypsin has remained unclear. In this study we cloned and
      sequenced trypsinogen-2 cDNA from human COLO 205 colon carcinoma cells and
      characterized the ability of the enzyme to activate latent human type IV
      procollagenases (proMMP-2 and proMMP-9). As shown by cloning and N-terminal amino
      acid sequencing, the amino acid sequence of tumor-associated trypsin-2 is
      identical to that of pancreatic trypsin-2. We found that both pancreatic trypsin
      2 and tumor cell-derived trypsin-2 are efficient activators of proMMP-9 and are
      capable of activating proMMP-9 at a molar ratio of 1:1000, the lowest reported so
      far. Human trypsin-2 was a more efficient activator than widely used bovine
      trypsin and converted the 92-kDa proMMP-9 to a single 77-kDa product that was not
      fragmented further. The single peptide bond cleaved by trypsin-2 in proMMP-9 was
      Arg87-Phe88. The generation of the 77-kDa species coincided with the increase in
      specific activity of MMP-9. In contrast, trypsin-2 only partially activated
      proMMP-2. Trypsin-2 cleaved the Arg99-Lys100 peptide bond of proMMP-2 generating
      62-65-kDa MMP-2 species. Trypsin-2-induced proMMP-2 and -9 conversions were
      inhibited by tumor-associated trypsin inhibitor added either prior to or during
      activation indicating that proMMPs were not activated autocatalytically. Trypsin
      2 also activated proMMPs associated with tissue inhibitor of matrix
      metalloproteinases, the complexes of which are thought to be the major MMP forms
      in vivo. The ability of human tumor cell-derived trypsin-2 to activate latent
      MMPs suggests a role for trypsin-2 in initiating the proteinase cascade that
      mediates tumor invasion and metastasis formation.

PMID- 9261111
TI  - Ligand interactions of the ArsC arsenate reductase.
AB  - ArsC encoded by Escherichia coli plasmid R773 catalyzes the reduction of arsenate
      to arsenite. The enzymatic reaction requires reduced glutathione and
      glutaredoxin. In this study a direct association between ArsC and glutaredoxin
      was demonstrated. An arsC gene with six histidine codons added to the 5' end of
      the gene was constructed, and the resulting ArsC enyzme was shown to be
      functional. Interaction of the histidine-tagged ArsC and glutaredoxin was
      examined by Ni2+ affinity chromatography. The association required the presence
      of reduced glutathione and either the substrate arsenate or a competitive
      inhibitor, phosphate or sulfate. A free thiolate on glutathione was not required.
      A tryptophan residue was introduced into ArsC at the 11th position, immediately
      adjacent to the active site Cys-12. Trp-11 fluorescence was quenched upon
      addition of arsenate. Addition of reduced glutathione after arsenate resulted in
      a rapid increase in fluorescence followed by a slower decay of the signal. These
      spectroscopic signals were specific for arsenate and reduced glutathione; neither
      competitive inhibitors nor non-thiol glutathione analogs produced this effect.
      Cys-12 thiolate was also required. Thus the intrinsic fluorescence of Trp-11
      provides a useful probe to investigate the mechanism of this novel reductase.

PMID- 9261110
TI  - Identification of an amiloride binding domain within the alpha-subunit of the
      epithelial Na+ channel.
AB  - Limited information is available regarding domains within the epithelial Na+
      channel (ENaC) which participate in amiloride binding. We previously utilized the
      anti-amiloride antibody (BA7.1) as a surrogate amiloride receptor to delineate
      amino acid residues that contact amiloride, and identified a putative amiloride
      binding domain WYRFHY (residues 278-283) within the extracellular domain of
      alpharENaC. Mutations were generated to examine the role of this sequence in
      amiloride binding. Functional analyses of wild type (wt) and mutant alpharENaCs
      were performed by cRNA expression in Xenopus oocytes and by reconstitution into
      planar lipid bilayers. Wild type alpharENaC was inhibited by amiloride with a Ki
      of 169 nM. Deletion of the entire WYRFHY tract (alpharENaC Delta278-283) resulted
      in a loss of sensitivity of the channel to submicromolar concentrations of
      amiloride (Ki = 26.5 microM). Similar results were obtained when either
      alpharENaC or alpharENaC Delta278-283 were co-expressed with wt beta- and
      gammarENaC (Ki values of 155 nM and 22.8 microM, respectively). Moreover,
      alpharENaC H282D was insensitive to submicromolar concentrations of amiloride (Ki
      = 6.52 microM), whereas alpharENaC H282R was inhibited by amiloride with a Ki of
      29 nM. These mutations do not alter ENaC Na+:K+ selectivity nor single-channel
      conductance. These data suggest that residues within the tract WYRFHY participate
      in amiloride binding. Our results, in conjunction with recent studies
      demonstrating that mutations within the membrane-spanning domains of alpharENaC
      and mutations preceding the second membrane-spanning domains of alpha-, beta-,
      and gammarENaC alters amiloride's Ki, suggest that selected regions of the
      extracellular loop of alpharENaC may be in close proximity to residues within the
      channel pore.

PMID- 9261112
TI  - The rat glucocorticoid receptor mutant K461A differentiates between two different
      mechanisms of transrepression.
AB  - The glucocorticoid receptor (GR) can both activate and repress transcription of
      target genes by interaction with specific genomic response elements,
      glucocorticoid response elements (GREs). Activation of transcription is usually
      the result of the direct interaction between GR and the GRE, whereas GR-mediated
      transcription repression is either the result of the indirect action of GR,
      mediated by a response element as a result of protein.protein interaction or by
      an occlusion mechanism in which GR displaces a general or regulatory
      transcription factor. A specific mutation of rat GR, K461A, has previously been
      described to transform the indirect protein.protein interaction-dependent
      transrepressive effect of GR into an activating function (Starr, D. B., Matsui,
      W., Thomas, J. R., and Yamamoto, K. R. (1996) Genes Dev. 10, 1271-1283). In HOS
      D4 and COS7 cells, this mutation was shown to transform the transrepressive
      effect of wild-type GR, acting on reporter constructs containing the composite
      GRE from the proliferin gene (plfG) or the negative tethering GRE from the
      collagenase A promoter (colA), into an activating function. In contrast, the
      K461A mutation had no effect on the transrepressive effect of GR on the human
      osteocalcin gene in which repression apparently occurs through the binding of GR
      to a negative GRE that overlaps the TATA box. The transrepressive function,
      typically 40% of the basal level in the absence of hormone, required only the
      isolated DNA-binding domain of wild type or mutant GR and was independent of the
      nature of transactivation domain. Thus, mutation of rat GR at position 461
      differentiates between transrepressive functions of GR dependent on GR.DNA
      interaction (repression by occlusion) and GR.protein interaction (active
      repression).

PMID- 9261113
TI  - Novel inhibitors of cytokine-induced IkappaBalpha phosphorylation and endothelial
      cell adhesion molecule expression show anti-inflammatory effects in vivo.
AB  - We have identified two compounds that inhibit the expression of endothelial
      leukocyte adhesion molecules intercellular adhesion molecule-1, vascular cell
      adhesion molecule-1, and E-selectin. These compounds act by inhibiting tumor
      necrosis factor-alpha-induced phosphorylation of IkappaB-alpha, resulting in
      decreased nuclear factor-kappaB and decreased expression of adhesion molecules.
      The effects on both IkappaB-alpha phosphorylation and surface expression of E
      selectin were irreversible and occurred at an IC50 of approximately 10 microM.
      These agents selectively and irreversibly inhibited the tumor necrosis factor
      alpha-inducible phosphorylation of IkappaB-alpha without affecting the
      constitutive IkappaB-alpha phosphorylation. Although these compounds exhibited
      other activities, including stimulation of the stress-activated protein kinases,
      p38 and JNK-1, and activation of tyrosine phosphorylation of a 130-140-kDa
      protein, these effects are probably distinct from the effects on adhesion
      molecule expression since they were reversible. One compound was evaluated in
      vivo and shown to be a potent anti-inflammatory drug in two animal models of
      inflammation. The compound reduced edema formation in a dose-dependent manner in
      the rat carrageenan paw edema assay and reduced paw swelling in a rat adjuvant
      arthritis model. These studies suggest that inhibitors of cytokine-inducible
      IkappaBalpha phosphorylation exert anti-inflammatory activity in vivo.

PMID- 9261114
TI  - Properties of a cyclosporin-insensitive permeability transition pore in yeast
      mitochondria.
AB  - Yeast mitochondria (Saccharomyces cerevisiae) contain a permeability transition
      pore which is regulated differently than the pore in mammalian mitochondria. In a
      mannitol medium containing 10 mM Pi and ethanol (oxidizable substrate), yeast
      mitochondria accumulate large amounts of Ca2+ (>400 nmol/mg of protein) upon the
      addition of an electrophoretic Ca2+ ionophore (ETH129). Pore opening does not
      occur following Ca2+ uptake, even though ruthenium red-inhibited rat liver
      mitochondria undergo rapid pore opening under analogous conditions. However, a
      pore does arise in yeast mitochondria when Ca2+ and Pi are not present, as
      monitored by swelling, ultrastructure, and matrix solute release. Pore opening is
      slow unless a respiratory substrate is provided (ethanol or NADH) but also occurs
      rapidly in response to ATP (2 mM) when oligomycin is present. Pi and ADP inhibit
      pore opening (EC50 approximately 1 and 4 mM, respectively), however, cyclosporin
      A (7 microg/ml), oligomycin (20 microg/ml), or carboxyatractyloside (25 microM)
      have no effect. The pore arising during respiration is also inhibited by
      nigericin or uncoupler, indicating that an acidic matrix pH antagonizes the
      process. Pi also inhibits pore opening by lowering the matrix pH (Pi/OH-
      antiport). However, inhibition of the ATP-induced pore by Pi is seen in the
      presence of mersalyl, suggesting a second mechanism of action. Since pore
      induction by ATP is not sensitive to carboxyatractyloside, ATP appears to act at
      an external site and Pi may antagonize the interaction. Isoosmotic polyethylene
      glycol-induced contraction of yeast mitochondria swollen during respiration, or
      in the presence of ATP, is 50% effective at a solute size of 1.0-1.1 kDa. This
      suggests that the same pore is induced in both cases and is comparable in size
      with the permeability transition pore of heart and liver mitochondria.

PMID- 9261115
TI  - Src kinase activity is regulated by the SHP-1 protein-tyrosine phosphatase.
AB  - Activation of the cellular Src tyrosine kinase depends upon dephosphorylation of
      the carboxyl-terminal inhibitory tyrosine phosphorylation site. Herein we show
      that Src isolated from human platelets and Jurkat T cells is preferentially
      dephosphorylated at its inhibitory phosphotyrosine site by the SHP-1 tyrosine
      phosphatase. The data also revealed association of Src with SHP-1 in both
      platelets and lymphocytes and the capacity of Src to phosphorylate SHP-1 and
      interact with the SHP-1 NH2-terminal SH2 domain in vitro. Analysis of Src
      activity in thymocytes from SHP-1-deficient motheaten and viable motheaten mice
      revealed this kinase activity to be substantially lower than that detected in
      wild-type thymocytes, but to be enhanced by in vitro exposure to SHP-1.
      Similarly, immunoblotting analysis of thymocyte Src expression before and after
      selective depletion of active Src protein indicated that the proportion of active
      relative to inactive Src protein is markedly reduced in motheaten compared with
      wild-type cells. These observations, together with the finding of reduced Src
      activity in HEY cells expressing a dominant negative form of SHP-1, provide
      compelling evidence that SHP-1 functions include the positive regulation of Src
      activation.

PMID- 9261116
TI  - The role of 3' poly(A) tail metabolism in tumor necrosis factor-alpha regulation.
AB  - In unstimulated RAW 264.7 macrophage-like cells, tumor necrosis factor-alpha (TNF
      alpha) mRNA was transcribed and accumulated in the cytoplasm, but the TNF-alpha
      transcripts failed to associate with polysomes, and TNF-alpha protein was not
      detected. Stimulation with lipopolysaccharide (LPS) induced an increase in TNF
      alpha transcription, cytoplasmic TNF-alpha mRNA accumulation, polysome
      association, and secretion of TNF-alpha protein. This process was associated with
      a 200-nucleotide increase in the apparent length of the TNF-alpha mRNA. The
      difference in TNF-alpha mRNA size was caused by marked truncation of the 3'
      poly(A) tail in unstimulated cells. Fully adenylated TNF-alpha mRNA appeared
      within 15 min of LPS stimulation. We speculate that removal of the poly(A) tail
      blocks initiation of TNF-alpha translation in unstimulated macrophages. LPS
      inactivates this process, allowing synthesis of translatable polyadenylated TNF
      alpha mRNA.

PMID- 9261118
TI  - Modulation of transcription factor Sp1 by cAMP-dependent protein kinase.
AB  - Transcription factor Sp1 is a phosphoprotein whose level and DNA binding activity
      are markedly increased in doxorubicin-resistant HL-60 (HL-60/AR) leukemia cells.
      The trans-activating and DNA binding properties of Sp1 in HL-60/AR cells are
      stimulated by cAMP-dependent protein kinase (PKA) and PKA agonists and inhibited
      by PKA antagonists as well as by the PKA regulatory subunit. Reporter gene
      activity under the control of the Sp1-dependent SV40 promoter is stimulated in
      insect cells transiently expressing Sp1 and PKA, and the DNA binding activity of
      recombinant Sp1 is activated by exogenous PKA in vitro. These results indicate
      that Sp1 is a cAMP-responsive transcription factor and that Sp1-dependent genes
      may be modulated through a cAMP-dependent signaling pathway.

PMID- 9261117
TI  - Dihydroceramide biology. Structure-specific metabolism and intracellular
      localization.
AB  - This study utilized fluorescent analogs to characterize the intracellular
      transport and metabolism of dihydroceramide (DH-Cer), an intermediate in de novo
      sphingolipid biosynthesis. When 6-[N-(7-nitro-2,1,3-benzoxadiazol-4
      yl)amino]hexanoyl-DH-Cer (C6-NBD-DH-Cer) was incubated with HT29, NRK, BHK, or HL
      60 cells, it was efficiently converted to dihydrosphingomyelin and
      dihydroglucosylceramide, and a number of other sphingolipids, with the nature of
      the products depending on the cell line. In addition, complex sphingolipids were
      formed that contained a desaturated (sphingosine) backbone, indicating that DH
      Cer (and/or its metabolites) were substrates for the desaturase(s) that introduce
      the 4,5-trans double bond. Based on the kinetics and inhibitor studies, double
      bond addition did not appear to occur with the complex sphingolipids directly,
      but rather, during turnover and resynthesis. The conversion of C6-NBD-DH-Cer to
      more complex sphingolipids was highly stereoselective for the natural D,erythro
      isomer of C6-NBD-DH-Cer. Interestingly, the stereochemistry of the sphingoid base
      backbone also affected the localization of fluorescent sphingolipids: the
      D,erythro species appeared in the Golgi apparatus, whereas other stereo-isomers
      accumulated in the endoplasmic reticulum. In addition to C6-NBD-Cer and C6-NBD-DH
      Cer, C6-NBD-4-D-hydroxy-DH-Cer gave rise to formation of complex sphingolipids
      and localized at the Golgi apparatus. These studies indicate that dihydroceramide
      is used as the initial backbone of complex (glyco)sphingolipids, perhaps to avoid
      build up of ceramide as an intermediate since this is such a potent bioactive
      compound. The stereoselectivity in transport and metabolism suggests that
      trafficking of ceramide is protein-directed rather than simply a consequence of
      vesicular membrane flow.

PMID- 9261119
TI  - Modification of arginine-198 in sarcoplasmic reticulum Ca2+-ATPase by 1,2
      cyclohexanedione causes inhibition of formation of the phosphoenzyme intermediate
      from inorganic phosphate.
AB  - Sarcoplasmic reticulum vesicles were modified with 1,2-cyclohexanedione (CHD), a
      specific arginine-modifying reagent, in sodium borate (pH 8.0 or 8.8).
      Phosphoenzyme formation from Pi in the Ca2+-ATPase (reversal of hydrolysis of the
      phosphoenzyme intermediate) was almost completely inhibited by the modification
      with CHD. Tight binding of F- and Mg2+ and high affinity binding of vanadate in
      the presence of Mg2+, either of which produces a transition state analog for
      phosphoenzyme formation from the magnesium-enzyme-phosphate complex, were also
      markedly inhibited. In contrast, phosphoenzyme formation from acetyl phosphate in
      the forward reaction was unaffected. The enzyme was appreciably protected by
      tight binding of F- and Mg2+ or by high affinity binding of vanadate in the
      presence of Mg2+, but not by the presence of 20 mM MgCl2 alone or 150 mM Pi
      alone, against the CHD-induced inhibition of phosphoenzyme formation from Pi.
      Peptide mapping of the tryptic digests, detection of peptides containing CHD
      modified arginyl residues with Girard's reagent T, sequencing, and mass
      spectrometry showed that Arg-198 was a single major residue protected by tight
      binding of F- and Mg2+ against the modification with CHD. These results indicate
      that modification of Arg-198 with CHD is responsible for at least a part (the
      portion reduced by the transition state analogs) of the CHD-induced inhibition of
      phosphoenzyme formation from Pi and suggest that Arg-198 is located in or close
      to the catalytic site in the transition state for phosphoenzyme formation from
      the magnesium-enzyme-phosphate complex.

PMID- 9261120
TI  - Mutually exclusive splicing generates two distinct isoforms of pig heart succinyl
      CoA synthetase.
AB  - We have identified two distinct cDNAs encoding the alpha-subunit of pig heart
      succinyl-CoA synthetase. The derived amino acid sequence of one of these,
      PHalpha57, is highly similar to the alpha-subunit of the rat liver precursor
      enzyme. The second cDNA, PHalpha108, was identical throughout its sequence with
      PHalpha57 except for a stretch of 108 nucleotides which replaced a 57 nucleotide
      sequence in PHalpha57. Coexpression of either alpha-subunit cDNA with a common
      pig heart beta-subunit cDNA produced isozymes with GTP-specific enzyme activity.
      The enzyme produced by the combination of PHalpha57 and the beta-subunit cDNA
      resembled the "native" enzyme purified from pig heart tissue. In contrast, the
      expressed enzyme from the combination with PHalpha108 was clearly distinguishable
      from the native enzyme by, for example, hydroxyapatite chromatography. Moreover,
      it was now apparent that this isoform had been observed in previous preparations
      of the native enzyme, but always in very low amounts and, thus, disregarded. We
      have shown further that the two mRNA transcripts arise from a single gene and are
      generated by mutually exclusive splicing. The production of the PHalpha108
      message involves the use of a non-canonical splice site pair, AT-AA. Finally, we
      provide evidence for tissue specific regulation in the splicing of the PHalpha108
      message.

PMID- 9261121
TI  - Relation between the turnover number for vinblastine transport and for
      vinblastine-stimulated ATP hydrolysis by human P-glycoprotein.
AB  - Considerable uncertainty surrounds the stoichiometry of coupling of ATP
      hydrolysis to drug pumping by P-glycoprotein, the multidrug transporter. To
      estimate relative turnovers for pumping of the drug vinblastine and ATP
      hydrolysis, we began by measuring the number of P-glycoprotein molecules on the
      surface of murine NIH3T3 cells expressing the human MDR1 gene. Fluorescence of
      cells treated with monoclonal antibody UIC2 was determined as a function of (i)
      amount of antibody at a fixed number of cells and (ii) increasing cell number at
      constant antibody. The two together gives 1.95 x 10(6) P-glycoprotein
      molecules/cell. Initial uptake rates of vinblastine +/- verapamil measure the
      ability of P-glycoprotein to extract vinblastine from the plasma membrane before
      it enters the cell. As a function of [vinblastine] at 37 degrees C, they give the
      maximum rate of this component of outward pumping as 2.1 x 10(6) molecules s-1
      cell-1 or a turnover number of 1.1 s-1. Initial rates of one-way efflux as a
      function of [vinblastine] at 25 degrees C +/- glucose give the maximum rate of
      this component of pumping as 0.59 x 10(6) molecules s-1 cell-1. The ratio of
      ATPase activity of P-glycoprotein at 37 and 25 degrees C is 4.6. Appropriating
      this ratio for pumping, maximum one-way efflux at 37 degrees C is 4.6 x 0.59 =
      2.7 x 10(6) molecules s-1 cell-1, a turnover number of 1.4 s-1. The vinblastine
      stimulated ATPase activity of P-glycoprotein has a turnover number of 3.5 s-1 at
      37 degrees C, giving 2.8 molecules of ATP hydrolyzed for every vinblastine
      molecule transported in a particular direction. These calculations involve
      several approximations, but turnover numbers for pumping of vinblastine and for
      vinblastine-stimulated ATP hydrolysis are comparable. Thus, ATP hydrolysis is
      probably directly linked to drug transport by P-glycoprotein.

PMID- 9261122
TI  - Characterization of non-peptide antagonist and peptide agonist binding sites of
      the NK1 receptor with fluorescent ligands.
AB  - Ligand recognition of the NK1 receptor (substance P receptor) by peptide agonist
      and non-peptide antagonist has been investigated and compared by the use of
      fluorescent ligands and spectrofluorometric methods. Analogues of substance P
      (SP) labeled with the environment-sensitive fluorescent group 5
      dimethylaminonaphthalene-1-sulfonyl (dansyl) at either position 3, 8, or 11 or
      with fluorescein at the Nalpha position were synthesized and characterized.
      Peptides modified at the alpha-amino group or at positions 3 or 11 conserved a
      relatively good affinity for NK1 and agonistic properties. Modification at
      position 8 resulted in an 18, 000-fold decrease in affinity. A fluorescent dansyl
      analogue of the non-peptide antagonist CP96,345 was prepared and characterized.
      The quantum yield of fluorescence for dansyl-CP96,345 was much higher than for
      any of the dansyl-labeled peptides indicating that the micro-environment of the
      binding site is more hydrophobic for the non-peptide antagonist than for the
      peptide agonists. Comparison of collisional quenching of fluorescence by the
      water-soluble hydroxy-Tempo compound showed that dansyl-CP96,345 is buried and
      virtually inaccessible to aqueous quenchers, whereas dansyl- or fluoresceinyl
      labeled peptides were exposed to the solvent. Anisotropy of all fluorescent
      ligands increased upon binding to NK1 indicating a restricted motional freedom.
      However, this increase in anisotropy was more pronounced for the dansyl attached
      to the non-peptide antagonist CP96,345 than for the fluorescent probes attached
      to different positions of SP. In conclusion, our data indicate that the
      environment surrounding non-peptide antagonist and peptide agonists are vastly
      different when bound to the NK1 receptor. These results support recent
      observations by mutagenesis and cross-linking work suggesting that peptide
      agonists have their major interaction points in the N-terminal extension and the
      loops forming the extracellular face of the NK1 receptor. Our data also suggest
      that neither the C terminus nor the N terminus of SP appears to penetrate deeply
      below the extracellular surface in the transmembrane domain of the receptor.

PMID- 9261123
TI  - Cell-surface interactions of echovirus 22.
AB  - Echovirus 22 (EV22) is a picornavirus forming a distinct molecular cluster
      together with echovirus 23. EV22 has an Arg-Gly-Asp (RGD) peptide motif in its
      capsid protein VP1; similar motifs are known to mediate many cell-cell and
      microbe-host interactions. To identify peptide sequences that specifically bind
      to EV22 and potentially play a role in receptor recognition, we have used here
      peptide libraries displayed in filamentous phage. We isolated an EV22-binding
      motif CLRSG(R/F)GC. The synthetic CLRSGRGC peptide was able to inhibit EV22
      infection. The infection was also inhibited by an RGD-containing peptide
      representing the C terminus of the EV22 capsid protein VP1 and CWDDGWLC (an RGD
      binding peptide; Pasqualini, R., Koivunen, E., and Ruoslahti, E. (1995) J. Cell
      Biol. 130, 1189-1196). As the EV22-recognizing sequence LRSG is found in the
      integrin beta1 chain and the entire LRSGRG hexapeptide occurs in the matrix
      metalloproteinase 9 (MMP-9), we carried out blocking experiments with anti
      integrin and anti-MMP-9 antibodies. EV22 infection could be blocked in cell
      cultures with anti-alphav, -beta1, and, to a lesser extent, with anti-MMP-9
      antibodies. These results imply that EV22 recognizes preferentially alphavbeta1
      integrin as a cellular receptor and MMP-9 may also play a role in the cell
      surface interactions of the virus.

PMID- 9261124
TI  - Synthesis of prostaglandin E2 ethanolamide from anandamide by cyclooxygenase-2.
AB  - Because of its structural similarity to polyunsaturated fatty acids, anandamide
      could serve as substrate for enzymes such as lipoxygenases and cyclooxygenases,
      which metabolize polyunsaturated fatty acids to potent bioactive metabolites.
      Here the ability of recombinant human cyclooxygenase-1 (hCOX-1) and
      cyclooxygenase-2 (hCOX-2) to metabolize anandamide was studied. Baculovirus
      expressed and -purified hCOX-2, but not hCOX-1, effectively oxygenated
      anandamide. Reverse phase high pressure liquid chromatography analysis of the
      products derived from 1-14C-labeled anandamide showed that the products formed
      are similar to those formed with arachidonic acid as substrate. The major
      prostanoid product derived from anandamide was determined by mass spectrometry to
      be prostaglandin E2 ethanolamide. Incubation of anandamide with lysates and the
      intact cell line expressing COX-2 but not that of COX-1 produced prostaglandin E2
      ethanolamide. These results demonstrate the existence of a COX-2-mediated pathway
      for anandamide metabolism, and the metabolites formed represent a novel class of
      prostaglandins.

PMID- 9261125
TI  - Transforming growth factor (TGF-beta)-specific signaling by chimeric TGF-beta
      type II receptor with intracellular domain of activin type IIB receptor.
AB  - Members of the transforming growth factor-beta (TGF-beta) superfamily signal via
      different heteromeric complexes of two sequentially acting serine/threonine
      kinase receptors, i.e. type I and type II receptors. We generated two different
      chimeric TGF-beta superfamily receptors, i.e. TbetaR-I/BMPR-IB, containing the
      extracellular domain of TGF-beta type I receptor (TbetaR-I) and the intracellular
      domain of bone morphogenetic protein type IB receptor (BMPR-IB), and TbetaR
      II/ActR-IIB, containing the extracellular domain of TGF-beta type II receptor
      (TbetaR-II) and the intracellular domain of activin type IIB receptor (ActR-IIB).
      In the presence of TGF-beta1, TbetaR-I/BMPR-IB and TbetaR-II/ActR-IIB formed
      heteromeric complexes with wild-type TbetaR-II and TbetaR-I, respectively, upon
      stable transfection in mink lung epithelial cell lines. We show that TbetaR
      II/ActR-IIB restored the responsiveness upon transfection in mutant cell lines
      lacking functional TbetaR-II with respect to TGF-beta-mediated activation of a
      transcriptional signal, extracellular matrix formation, growth inhibition, and
      Smad phosphorylation. Moreover, TbetaR-I/BMPR-IB and TbetaR-II/ActR-IIB formed a
      functional complex in response to TGF-beta and induced phosphorylation of Smad1.
      However, complex formation is not enough for signal propagation, which is shown
      by the inability of TbetaR-I/BMPR-IB to restore responsiveness to TGF-beta in
      cell lines deficient in functional TbetaR-I. The fact that the TGF-beta1-induced
      complex between TbetaR-II/ActR-IIB and TbetaR-I stimulated endogenous Smad2
      phosphorylation, a TGF-beta-like response, is in agreement with the current model
      for receptor activation in which the type I receptor determines signal
      specificity.

PMID- 9261126
TI  - Inhibition of thymidine transport in dnaA mutants of Escherichia coli.
AB  - DnaA protein is the initiator of chromosomal DNA replication in Escherichia coli.
      We report here our evidence that thymidine transport across cytoplasmic membranes
      in temperature-sensitive dnaA mutants is greatly decreased at a permissive
      temperature for growth of the mutants. Complementation analysis with a plasmid
      containing the wild type dnaA gene and P1 phage-mediated transduction confirmed
      that mutations in the dnaA gene were responsible for the phenotype. A low level
      of nucleoside transport in the dnaA mutant was specific for thymidine; transport
      activities for other nucleosides were much the same as those in wild type cells.
      Membrane vesicles prepared from the dnaA mutant showed much the same activity of
      thymidine transport as did those from the wild type cells. No significant
      difference in the activity of thymidine kinase, which is known to facilitate
      thymidine transport, was seen between the mutant and the wild type cells. An
      increase in the pool of dTTP, a negative regulator for thymidine kinase, was
      observed in the dnaA mutant. Based on these observations, we suggest that
      inhibition of thymidine transport in dnaA mutants is caused by increases in the
      dTTP pool.

PMID- 9261127
TI  - High potency antagonists of the pancreatic glucagon-like peptide-1 receptor.
AB  - GLP-1-(7-36)-amide and exendin-4-(1-39) are glucagon-like peptide-1 (GLP-1)
      receptor agonists, whereas exendin-(9-39) is the only known antagonist. To
      analyze the transition from agonist to antagonist and to identify the amino acid
      residues involved in ligand activation of the GLP-1 receptor, we used exendin
      analogs with successive N-terminal truncations. Chinese hamster ovary cells
      stably transfected with the rat GLP-1 receptor were assayed for changes in
      intracellular cAMP caused by the test peptides in the absence or presence of half
      maximal stimulatory doses of GLP-1. N-terminal truncation of a single amino acid
      reduced the agonist activity of the exendin peptide, whereas N-terminal
      truncation of 3-7 amino acids produced antagonists that were 4-10-fold more
      potent than exendin-(9-39). N-terminal truncation of GLP-1 by 2 amino acids
      resulted in weak agonist activity, but an 8-amino acid N-terminal truncation
      inactivated the peptide. Binding studies performed using 125I-labeled GLP-1
      confirmed that all bioactive peptides specifically displaced tracer with high
      potency. In a set of exendin/GLP-1 chimeric peptides, substitution of GLP-1
      sequences into exendin-(3-39) produced loss of antagonist activity with
      conversion to a weak agonist. The results show that receptor binding and
      activation occur in separate domains of exendin, but they are more closely
      coupled in GLP-1.

PMID- 9261128
TI  - Impact of overexpression of the reduced folate carrier (RFC1), an anion
      exchanger, on concentrative transport in murine L1210 leukemia cells.
AB  - Transport of reduced folates in murine leukemia cells is mediated by the
      bidirectional reduced folate carrier (RFC1) and independent unidirectional exit
      pumps. RFC1 has been proposed to be intrinsically equilibrating, generating
      transmembrane gradients by exchange with inorganic and organic anions. This paper
      defines the role of high level carrier expression, through transfection with RFC1
      cDNA, on concentrative transport of the folate analog, methotrexate (MTX) in
      murine L1210 leukemia cells. RFC1 was expressed in the MTXrA line, which lacks a
      functional endogenous carrier to obtain the MTXrA-R16 clonal derivative. Influx
      was increased approximately 9-fold in MTXrA-R16 cells without a change in Km. The
      efflux rate constant was increased by a factor of 5.1 relative to L1210 cells,
      and this resulted in only a 2.1-fold increase in the steady-state level of free
      intracellular MTX, [MTX]i, when [MTX]e was 1 microM. The concentrative advantage
      for RFC1 (the ratio of [MTX]i in MTXrA-R16 to L1210 cells) increased from 1.8 at
      0.1 microM MTX to 3.8 at an [MTX]e level of 30 microM. Augmented transport in
      MTXrA-R16 cells was accompanied by a 2-fold increase in accumulation of MTX
      polyglutamate derivatives and a approximately 50% decrease in the EC50 for 5
      formyltetrahydrofolate and folic acid and the MTX IC50 relative to L1210 cells.
      These alterations paralleled changes in [MTX]i and not the much larger change in
      influx at low [MTX]e levels, consistent with the critical role that free
      intracellular folates and drug play in meeting cellular needs for folates and as
      a determinant of antifolate activity, respectively. The data indicate that RFC1
      produces a large and near symmetrical increase in the bidirectional fluxes of MTX
      resulting in only a small increase in the transmembrane chemical gradient at low
      extracellular folate levels. Hence, increased expression of RFC1, alone, may not
      be an efficient adaptive response to folate deprivation, and other factors may
      come into play to account for the marked increases in concentrative folate
      transport which occur when cells are subjected to low folate-selective pressure.

PMID- 9261129
TI  - Folding of the glucocorticoid receptor by the heat shock protein (hsp) 90-based
      chaperone machinery. The role of p23 is to stabilize receptor.hsp90
      heterocomplexes formed by hsp90.p60.hsp70.
AB  - In cytosols from animal and plant cells, the abundant heat shock protein hsp90 is
      associated with several proteins that act together to assemble steroid receptors
      into receptor.hsp90 heterocomplexes. We have reconstituted a minimal
      receptor.hsp90 assembly system containing four required components, hsp90, hsp70,
      p60, and p23 (Dittmar, K. D., Hutchison, K. A., Owens-Grillo, J. K., and Pratt,
      W. B. (1996) J. Biol. Chem. 271, 12833-12839). We have shown that hsp90, p60, and
      hsp70 are sufficient for carrying out the folding change that converts the
      glucocorticoid receptor (GR) hormone binding domain (HBD) from a non-steroid
      binding to a steroid binding conformation, but to form stable GR.hsp90
      heterocomplexes, p23 must also be present in the incubation mix (Dittmar, K. D.,
      and Pratt, W. B. (1997) J. Biol. Chem. 272, 13047-13054). In this work, we show
      that addition of p23 to native GR.hsp90 heterocomplexes immunoadsorbed from L
      cell cytosol or to GR.hsp90 heterocomplexes prepared with the minimal
      (hsp90.p60.hsp70) assembly system inhibits both receptor heterocomplex
      disassembly and loss of steroid binding activity. p23 stabilizes the GR.hsp90
      heterocomplex in a dynamic and ATP-independent manner. In contrast to hsp90 that
      is bound to the GR, free hsp90 binds p23 in an ATP-dependent manner, and hsp90 in
      the hsp90.p60.hsp70 heterocomplex is in a conformation that does not bind p23 at
      all. The effect of p23 in the minimal GR heterocomplex assembly system is to
      stabilize GR.hsp90 heterocomplexes once they are formed and it does not appear to
      affect the rate of heterocomplex assembly. Molybdate has the same ability as p23
      to stabilize GR heterocomplexes with mammalian hsp90, but GR heterocomplexes with
      plant hsp90 are stabilized by p23 and not by molybdate. We propose that
      incubation of the GR with hsp90.p60.hsp70 forms a GR.hsp90 heterocomplex in which
      hsp90 is in an ATP-dependent conformation. The ATP-dependent conformation of
      hsp90 is required for the hormone binding domain to have a steroid binding site,
      and binding of p23 to that state of hsp90 stabilizes the GR.hsp90 heterocomplex
      to inactivation and disassembly.

PMID- 9261130
TI  - Glycine N-methyltransferase is an example of functional diversity. Role as a
      polycyclic aromatic hydrocarbon-binding receptor.
AB  - The cytochrome P-4501A1 (CYP1A1) gene is regulated by several trans-acting
      factors including the 4 S polycyclic aromatic hydrocarbon (PAH)-binding protein,
      which has recently been identified as glycine N-methyltransferase (GNMT) (Raha,
      A., Wagner, C., Macdonald, R. G., and Bresnick, E. (1994) J. Biol. Chem. 269,
      5750-5756). The role of GNMT as a 4 S PAH-binding protein in mediating the
      induction of cytochrome P-4501A1 has been investigated further. GNMT cDNA, which
      was cloned into a pMAMneo vector containing the Rous sarcoma virus promoter and
      the neomycin resistance gene, was stably transfected into D422 Chinese hamster
      ovary (CHO) cells. Several positive clones were selected by reverse transcription
      polymerase chain reaction and assayed for the expression of recombinant protein.
      Western blot analysis indicated the expression of significant levels of the 4 S
      protein in the stably transfected CHO cells (CHO-GNMT). Cytosolic preparations
      from the CHO-GNMT showed high benzo[a]pyrene (B[a]P) binding but no 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) binding activity when compared with clones
      transfected with the pMAMneo vector alone (CHO-neo) or the parental CHO cells.
      Challanging the CHO-GNMT cells with 4 microM B[a]P resulted in elevated levels of
      CYP1A1 mRNA. Equally effective in inducing CYP1A1 mRNA were benzo[e]pyrene and 3
      methylcholanthrene. On the other hand, TCDD did not induce CYP1A1 gene expression
      in these cells. B[a]P-treated CHO-GNMT, expressing the 4 S protein, also showed
      CYP1A1 protein by Western blotting and exhibited ethoxyresorufin-O-deethylase
      activity; neither the CHO-neo or parental CHO cells were positive for any of
      these measures. No Ah receptor message or protein was detectable in the parental
      CHO, CHO-neo, or CHO-GNMT cells. Furthermore, no XRE binding activity was
      observed in TCDD-treated cytosolic preparations or nuclear extracts from CHO-GNMT
      cells that were treated with TCDD. These studies unequivocally establish that
      GNMT is a PAH-binding protein that can mediate the induction of CYP1A1 by PAHs
      such as B[a]P through an Ah receptor-independent pathway.

PMID- 9261131
TI  - Opposite effect of intracellular Ca2+ and protein kinase C on the expression of
      inwardly rectifying K+ channel 1 in mouse skeletal muscle.
AB  - The level of inwardly rectifying K+ channel 1 (IRK1) mRNA decreased upon
      denervation and increased during muscle differentiation in mouse skeletal muscle.
      To identify the mechanism(s) underlying the regulation of IRK1 mRNA expression,
      we examined its expression using the well differentiated C2C12 mouse skeletal
      muscle cell line as a model system. Since nerve-induced muscle activity results
      in contraction, it was questioned whether the changes in IRK1 expression might be
      relevant to the increased intracellular calcium that functions as a cytoplasmic
      messenger in excitation-contraction coupling. Indeed, activation of either L-type
      calcium channels or ryanodine receptors increased the level of IRK1 mRNA. More
      directly, ionomycin activated the IRK1 expression in time- and dose-dependent
      manners, which was abolished by treatment with EGTA. Genistein, a tyrosine kinase
      inhibitor, also abolished the stimulating effect of ionomycin. Meanwhile,
      activation of protein kinase C by 12-O-tetradecanoylphorbol acetate (TPA)
      markedly decreased the level of IRK1 mRNA, which required ongoing protein
      synthesis. Actinomycin D experiments revealed that ionomycin increased the half
      life of IRK1 mRNA from 0.86 to 1.97 h, but TPA decreased it to 0.38 h. However,
      neither ionomycin nor TPA appreciably altered the rate of IRK1 gene
      transcription. Based on these observations, we conclude that intracellular
      calcium and protein kinase C are oppositely involved in the muscle activity
      dependent regulation of IRK1 gene expression and that both act at the level of
      mRNA stability.

PMID- 9261132
TI  - Dimerization interactions of the b subunit of the Escherichia coli F1F0-ATPase.
AB  - Site-directed mutagenesis and N-terminal truncations were used to examine
      dimerization interactions in the b subunit of Escherichia coli F1F0-ATPase.
      Individual cysteine residues were incorporated into bsyn, a soluble form of the
      protein lacking the membrane-spanning N-terminal domain, in two main areas: the
      heptad repeat region and the hydrophobic region which begins at residue Val-124.
      The tendencies of these cysteine residues to form disulfide bonds with the
      corresponding cysteine in the bsyn dimer were tested using disulfide exchange by
      glutathione and air oxidation catalyzed by Cu2+. Within the heptad repeat region,
      only cysteines at residues 59 and 60, which occupy the b and c positions of the
      heptad repeat, showed significant tendencies to form disulfides, a result
      inconsistent with a coiled-coil model for bsyn. Mixed disulfide formation most
      readily occurred with the S60C + L65C and A61C + L65C pairs. Cysteines at
      positions 124, 128, 132, and 139 showed strong tendencies to form disulfides with
      their mates in the dimer, suggesting a parallel alpha-helical interaction between
      the subunits in this region. Deletion of residues N-terminal to either Glu-34 or
      Asp-53 had no apparent effect on dimerization as determined by sedimentation
      equilibrium, while deletion of all residues N-terminal to Lys-67 produced a
      monomeric form. These results imply that residues 53-66 but not 24-52 are
      essential for bsyn dimerization. Taken together the results are consistent with a
      model in which the two b subunits interact in more than one region, including a
      parallel alignment of helices containing residues 124-139.

PMID- 9261133
TI  - Guanosine tetra- and pentaphosphate promote accumulation of inorganic
      polyphosphate in Escherichia coli.
AB  - High levels of guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate
      (pppGpp), generated in response to amino acid starvation in Escherichia coli,
      lead to massive accumulations of inorganic polyphosphate (polyP). Inasmuch as the
      activities of the principal enzymes that synthesize and degrade polyP fluctuate
      only slightly, the polyP accumulation can be attributed to a singular and
      profound inhibition by pppGpp and/or ppGpp of the hydrolytic breakdown of polyP
      by exopolyphosphatase, thereby blocking the dynamic turnover of polyP. The Ki
      values of 10 microM for pppGpp and 200 microM for ppGpp are far below the
      concentrations of these nucleotides in nutritionally stressed cells. In the
      complex metabolic network of pppGpp and ppGpp, the greater inhibitory effect of
      pppGpp (compared with ppGpp) leading to the accumulation of polyP, may have some
      significance in the relative roles played by these regulatory compounds.

PMID- 9261134
TI  - Characterization of a novel iodocyanopindolol and SM-11044 binding protein, which
      may mediate relaxation of depolarized rat colon tonus.
AB  - Studies under blockade of alpha-, beta1-, and beta2-adrenoreceptors revealed a
      good correlation between the responses of rat colon relaxation of depolarized
      tonus and of rat adipocyte lipolysis elicited by catecholamines or BRL-37344, a
      selective beta3-adrenoreceptor agonist, suggesting beta3-adrenoreceptor
      stimulation. In contrast, SM-11044, a nonselective beta-adrenoreceptor agonist,
      stimulated colon relaxation more efficiently than lipolysis; its effects were
      differently antagonized by cyanopindolol with pA2 values of 8.31 in colon and of
      7.32 in adipocytes. Binding studies in rat colon smooth muscle membranes using
      [125I]iodocyanopindolol under blockade of adrenaline and serotonin receptors
      revealed the existence of a single class of sites (Kd = 11.0 nM, Bmax = 716.7
      fmol/mg protein). The specific binding was saturable and reversible and was
      displaced by SM-11044 but not by BRL-37344, isoproterenol, noradrenaline,
      adrenaline, serotonin, nor dopamine. This binding site was photoaffinity labeled
      using [125I]iodocyanopindolol-diazirine. The labeling was prevented by SM-11044
      but not by BRL-37344. The amino-terminal amino acid sequences of the high
      performance liquid chromatography-purified peptides generated by enzymatic and
      chemical cleavages of the affinity labeled 34-kDa protein confirmed that the
      novel iodocyanopindolol or SM-11044 binding protein of rat colon smooth muscle
      membranes is different from known adrenaline, serotonin, or dopamine receptors.
      Its functional role might include the relaxation of depolarized colon.

PMID- 9261135
TI  - Transgenic mice with cardiac overexpression of alpha1B-adrenergic receptors. In
      vivo alpha1-adrenergic receptor-mediated regulation of beta-adrenergic signaling.
AB  - Transgenic mice were generated with cardiac-specific overexpression of the wild
      type (WT) alpha1B-adrenergic receptor (AR) using the murine alpha-myosin heavy
      chain gene promoter. Previously, we described transgenic mice with alpha-myosin
      heavy chain-directed expression of a constitutively active mutant alpha1B-AR that
      had a phenotype of myocardial hypertrophy (Milano, C. A., Dolber, P. C., Rockman,
      H. A., Bond, R. A., Venable M. E., Allen, L. F., and Lefkowitz, R. J. (1994)
      Proc. Natl. Acad. Sci. U. S. A. 91, 10109-10113). In animals with >40-fold WT
      alpha1-AR overexpression, basal myocardial diacylglycerol content was
      significantly increased, indicating enhanced alpha1-adrenergic signaling and
      phospholipase C activity. In contrast to the mice overexpressing constitutively
      active mutant alpha1B-ARs, the hearts of these mice did not develop cardiac
      hypertrophy despite an 8-fold increase in ventricular mRNA for atrial natriuretic
      factor. In vivo physiology was studied in anesthetized intact animals and showed
      left ventricular contractility in response to the beta-agonist isoproterenol to
      be significantly depressed in animals overexpressing WT alpha1B-ARs. Membranes
      purified from the hearts of WT alpha1BAR-overexpressing mice demonstrated
      significantly attenuated adenylyl cyclase activity basally and after stimulation
      with isoproterenol, norepinephrine, or phenylephrine. Interestingly, these in
      vitro changes in signaling were reversed after treating the mice with pertussis
      toxin, suggesting that the extraordinarily high levels of WT alpha1B-ARs can lead
      to coupling to pertussis toxin-sensitive G proteins. Another potential
      contributor to the observed decreased myocardial signaling and function could be
      enhanced beta-AR desensitization as beta-adrenergic receptor kinase (betaARK1)
      activity was found to be significantly elevated (>3-fold) in myocardial extracts
      isolated from WT alpha1B-AR-overexpressing mice. This type of altered signal
      transduction may become critical in disease conditions such as heart failure
      where betaARK1 levels are elevated and beta-ARs are down-regulated, leading to a
      higher percentage of cardiac alpha1-ARs. Thus, these mice serve as a unique
      experimental model to study the in vivo interactions between alpha- and beta-ARs
      in the heart.

PMID- 9261136
TI  - Multiple and essential Sp1 binding sites in the promoter for transforming growth
      factor-beta type I receptor.
AB  - Maximal gene expression driven by the promoter for the transforming growth factor
      beta type I receptor (TGF-betaRI) occurs with a 1. 0-kilobase pair fragment
      immediately upstream of exon 1. This region lacks a typical TATA box but contains
      CCAAT boxes, multiple Sp1, and PEBP2/CBFalpha binding sites among other possible
      cis-acting elements. Alterations within two CCAAT box sequences do not mitigate
      reporter gene expression driven by the basal promoter, and no nuclear factor
      binds to oligonucleotides encompassing these sites. In contrast, other deletions
      or site-specific mutations reveal an essential Sp1 site in the basal promoter and
      several dispersed upstream Sp1 sites that contribute to maximal reporter gene
      expression. The proportions of transcription factors Sp1 and Sp3, and their
      ratios of binding to consensus elements, are maintained in bone cells at
      different stages of differentiation. Finally, nuclear factor that binds to
      PEBP2/CBFalpha-related cis-acting elements in the basal promoter sequence also
      occurs in osteoblasts. Our studies reveal that constitutive expression of TGF
      betaRI may be determined by constitutive nuclear factor binding to Sp1 sites,
      whereas other elements may account for the variations in TGF-betaRI levels that
      parallel changes in bone cell differentiation or activity.

PMID- 9261137
TI  - Insulin-like growth factor-I-mediated neurite outgrowth in vitro requires mitogen
      activated protein kinase activation.
AB  - Insulin-like growth factor-I (IGF-I) induces neuronal differentiation in vitro.
      In the present study, we examined the signaling pathway underlying IGF-I-mediated
      neurite outgrowth. In SH-SY5Y human neuroblastoma cells, treatment with IGF-I
      induced concentration- and time-dependent tyrosine phosphorylation of the type I
      IGF receptor (IGF-IR) and extracellular signal-regulated protein kinases (ERK) 1
      and 2. These effects of IGF-I were blocked by a neutralizing antibody against IGF
      IR. Whereas IGF-IR phosphorylation was observed within 1 min, maximal
      phosphorylation of ERKs was not reached for 30 min. Both IGF-IR and ERK
      phosphorylation were maintained for at least 24 h. Also, the concentration
      dependence of IGF-I-stimulated IGF-IR and ERK tyrosine phosphorylation paralleled
      that of IGF-I-mediated neurite outgrowth. We further examined the role of mitogen
      activated protein kinase activation in IGF-I-stimulated neuronal differentiation
      using the mitogen-activated protein kinase/ERK kinase inhibitor PD98059. Whereas
      PD98059 had no effect on IGF-IR phosphorylation, PD98059 reduced IGF-I-mediated
      ERK tyrosine phosphorylation and ERK phosphorylation of the substrate Elk-1.
      PD98059 also produced a parallel reduction of IGF-I-stimulated neurite outgrowth.
      Finally, consistent with its ability to block neuronal differentiation, PD98059
      inhibited IGF-I-dependent changes of GAP-43 and c-myc gene expression. Together
      these results suggest that activation of ERKs is essential for IGF-I-stimulated
      neuronal differentiation.

PMID- 9261138
TI  - Protein kinase C-mediated interphase lamin B phosphorylation and solubilization.
AB  - Disassembly of the sperm nuclear envelope at fertilization is one of the earliest
      events in the development of the male pronucleus. We report that nuclear lamina
      disassembly in interphase sea urchin egg cytosol is a result of lamin B
      phosphorylation mediated by protein kinase C (PKC). Lamin B of permeabilized sea
      urchin sperm nuclei incubated in fertilized egg G1 phase cytosolic extract is
      phosphorylated within 1 min of incubation and solubilized prior to sperm
      chromatin decondensation. Phosphorylation is Ca2+-dependent. It is reversibly
      inhibited by the PKC-specific inhibitor chelerythrine, a PKC pseudosubstrate
      inhibitor peptide, and a PKC substrate peptide, but not by inhibitors of PKA,
      p34(cdc2) or calmodulin kinase II. Phosphorylation is inhibited by
      immunodepletion of cytosolic PKC and restored by addition of purified rat brain
      PKC. Sperm lamin B is a substrate for rat brain PKC in vitro, resulting in lamin
      B solubilization. Two-dimensional phosphopeptide maps of lamin B phosphorylated
      by the cytosolic kinase and by purified rat PKC are virtually identical. These
      data suggest that PKC is the major kinase required for interphase disassembly of
      the sperm lamina.

PMID- 9261140
TI  - Structural and functional requirements for agonist-induced internalization of the
      human platelet-activating factor receptor.
AB  - The receptor for platelet-activating factor (PAF) is a member of the G-protein
      coupled receptor family. To study the structural elements and mechanisms involved
      in the internalization of human PAF receptor (hPAFR), we used the following
      mutants: a truncated mutant in the C-terminal tail of the receptor (Cys317 -->
      Stop) and mutations in the (D/N)P(X)2,3Y motif (Asp289 --> Asn,Ala and Tyr293 -->
      Phe,Ala). Chinese hamster ovary cells expressing the Cys317 --> Stop mutant
      exhibited a marked reduction in their capacity to internalize PAF, suggesting the
      existence of determinants important for endocytosis in the last 26 amino acids of
      the cytoplasmic tail. Substitution of Asp289 to alanine abolished both
      internalization and G-protein coupling, whereas substitution of Tyr293 to alanine
      abolished coupling but not internalization. Inhibition or activation of protein
      kinase C did not significantly affect the internalization process. Receptor
      sequestration and ligand uptake was, at least in part, blocked by concanavalin A
      and blockers of endocytosis mediated by clathrin-coated pits. Our data suggest
      that the internalization of a G-protein-coupled receptor and coupling to a G
      protein can be two independent events. Moreover, the C terminus tail of hPAFR,
      but not the putative internalization motifs, may be involved in the
      internalization of hPAFR.

PMID- 9261139
TI  - The 90-kDa ribosomal S6 kinase (pp90rsk) phosphorylates the N-terminal regulatory
      domain of IkappaBalpha and stimulates its degradation in vitro.
AB  - Nuclear factor kappaB (NF-kappaB) is a eukaryotic member of the Rel family of
      transcription factors whose biological activity is post-translationally regulated
      by its assembly with various ankyrin-rich cytoplasmic inhibitors, including
      IkappaBalpha. Expression of NF-kappaB in the nucleus occurs after signal-induced
      phosphorylation, ubiquitination, and proteasome-mediated degradation of
      IkappaBalpha. The induced proteolysis of IkappaBalpha unmasks the nuclear
      localization signal within NF-kappaB, allowing its rapid migration into the
      nucleus, where it activates the transcription of many target genes. At present,
      the identity of the IkappaBalpha kinase(s) that triggers the first step in
      IkappaBalpha degradation remains unknown. We have investigated the potential
      function of the 90-kDa ribosomal S6 kinase, or pp90(rsk), as a signal-inducible
      IkappaBalpha kinase. pp90(rsk) lies downstream of mitogen-activated protein (MAP)
      kinase in the well characterized Ras-Raf-MEK-MAP kinase pathway that is induced
      by various growth factors and phorbol ester. We now show that pp90(rsk), but not
      pp70(S6K) or MAP kinase, phosphorylates the regulatory N terminus of IkappaBalpha
      principally on serine 32 and triggers effective IkappaBalpha degradation in
      vitro. When co-expressed in vivo in COS cells, IkappaBalpha and pp90(rsk) readily
      assemble into a complex that is immunoprecipitated with antibodies specific for
      either partner. While phorbol 12-myristate 13-acetate produced rapid activation
      of pp90(rsk), in vivo, other potent NF-kappaB inducers, including tumor necrosis
      factor alpha and the Tax transactivator of human T-cell lymphotrophic virus, type
      I, failed to activate pp90(rsk). These data suggest that more than a single
      IkappaBalpha kinase exists within the cell and that these IkappaBalpha kinases
      are differentially activated by different NF-kappaB inducers.

PMID- 9261141
TI  - Kinetic and spectroscopic analyses of mutants of a conserved histidine in the
      metallophosphatases calcineurin and lambda protein phosphatase.
AB  - Calcineurin belongs to a family of serine/threonine protein phosphatases that
      contain active site dinuclear metal cofactors. Bacteriophage lambda protein
      phosphatase is also considered to be a member of this family based on sequence
      comparisons (Lohse, D. L., Denu, J. M., and Dixon, J. E. (1995) Structure 3, 987
      990). Using EPR spectroscopy, we demonstrate that lambda protein phosphatase
      accommodates a dinuclear metal center. Calcineurin and lambda protein phosphatase
      likewise contain a conserved histidine that is not a metal ligand but is within 5
      A of either metal in calcineurin. In this study the conserved histidine in
      calcineurin was mutated to glutamine and the mutant protein analyzed by EPR
      spectroscopy and kinetic methods. Parallel studies with an analogous lambda
      protein phosphatase mutant were also carried out. Kinetic studies using
      paranitrophenyl phosphate as substrate showed a decrease in kcat of 460- and 590
      fold for the calcineurin and lambda protein phosphatase mutants, respectively,
      compared with the wild type enzymes. With a phosphopeptide substrate, mutagenesis
      of the conserved histidine resulted in a decrease in kcat of 1,300-fold for
      calcineurin. With the analogous lambda protein phosphatase mutant, kcat decreased
      530-fold compared with wild type lambda protein phosphatase using phenyl
      phosphate as a substrate. EPR studies of the iron-reconstituted enzymes indicated
      that although both mutant enzymes can accommodate a dinuclear metal center,
      spectroscopic differences compared with wild type proteins suggest a perturbation
      of the ligand environment, possibly by disruption of a hydrogen bond between the
      histidine and a metal-coordinated solvent molecule.

PMID- 9261142
TI  - Oxidation of low density lipoprotein particles decreases their ability to bind to
      human aortic proteoglycans. Dependence on oxidative modification of the lysine
      residues.
AB  - Oxidation of low density lipoprotein (LDL) leads to its rapid uptake by
      macrophages in vitro, but no detailed studies have addressed the effect of
      oxidation on the binding of LDL to proteoglycans. We therefore treated LDL with
      various substances: copper sulfate, 2,2'-azobis(2-amidinopropane)hydrochloride
      (AAPH), soybean lipoxygenase, and mouse peritoneal macrophages, and determined
      the extent to which the oxidatively modified LDL bound to human aortic
      proteoglycans in an affinity column. Oxidation of LDL with copper, AAPH, or
      macrophages, all of which increased its electrophoretic mobility, was associated
      with reduced binding to proteoglycans, until strongly oxidized LDL was totally
      unable to bind to them. After treatment of LDL with soybean lipoxygenase, the
      change in electrophoretic mobility was small, and the amount of binding to
      proteoglycans was only slightly decreased. The increased electrophoretic mobility
      of oxidized LDL reflects modification of the lysine residues of apolipoprotein B
      100 (apoB-100). To mimic the oxidative modification of lysines, we treated LDL
      with malondialdehyde. This treatment also totally prevented the binding of LDL to
      proteoglycans. In contrast, if the lysine residues of apoB-100 were methylated to
      shield them against oxidative modification, subsequent treatment of LDL with
      copper sulfate failed to reduce the degree of LDL binding to proteoglycans.
      Finally, the active lysine residues in the oxidized LDL particles, which are
      thought to be involved in this binding, were quantified with NMR spectroscopy. In
      oxidized LDL, the number of these residues was found to be decreased. The present
      results show that, after modification of the lysine residues of apoB-100 during
      oxidation, the binding of LDL to proteoglycans is decreased, and suggest that
      oxidation of LDL tends to lead to intracellular rather than extracellular
      accumulation of LDL during atherogenesis.

PMID- 9261143
TI  - Human thyroid-stimulating hormone (hTSH) subunit gene fusion produces hTSH with
      increased stability and serum half-life and compensates for mutagenesis-induced
      defects in subunit association.
AB  - The human thyroid-stimulating hormone (hTSH) subunits alpha and beta are
      transcribed from different genes and associate noncovalently to form the
      bioactive hTSH heterodimer. Dimerization is rate-limiting for hTSH secretion, and
      dissociation leads to hormone inactivation. Previous studies on human chorionic
      gonadotropin (hCG) and human follicle-stimulating hormone had shown that it was
      possible by subunit gene fusion to produce a bioactive, single chain hormone.
      However, neither the stability nor the clearance from the circulation of such
      fused glycoprotein hormones has been studied. We show here that genetic fusion of
      the hTSH alpha- and beta-subunits using the carboxyl-terminal peptide of the hCG
      beta-subunit as a linker created unimolecular hTSH whose receptor binding and
      bioactivity were comparable to native hTSH. Interestingly, the fused hTSH had
      higher thermostability and a longer plasma half-life than either native or
      dimeric hTSH containing the hCG beta-subunit-carboxyl-terminal peptide,
      suggesting that dimer dissociation may contribute to glycoprotein hormone
      inactivation in vivo. In addition, we show for the first time that synthesis of
      hTSH as a single polypeptide chain could overcome certain mutagenesis-induced
      defects in hTSH secretion, therefore enabling functional studies of such mutants.
      Thus, in addition to prolongation of plasma half-life, genetic fusion of hTSH
      subunits should be particularly relevant for the engineering of novel analogs
      where desirable features are offset by decreased dimer formation or stability.
      Such methods provide a general approach to expand the spectrum of novel
      recombinant glycoprotein hormones available for in vitro and in vivo study.

PMID- 9261144
TI  - Differential coupling of muscarinic m2 and m3 receptors to adenylyl cyclases V/VI
      in smooth muscle. Concurrent M2-mediated inhibition via Galphai3 and m3-mediated
      stimulation via Gbetagammaq.
AB  - Muscarinic m2 and m4 receptors couple preferentially to inhibition of adenylyl
      cyclase, whereas m1, m3, and m5 receptors couple preferentially to activation of
      phospholipase C-beta and in some cells to stimulation of cAMP. Smooth muscle
      cells were shown to express adenylyl cyclases types V and/or VI. Acetylcholine
      (ACh) stimulated the binding of [35S]GTPgammaS.Galpha complexes in smooth muscle
      membranes to Galphaq/11 and Galphai3 antibody. Binding to Galphaq/11 antibody was
      inhibited by the m3 receptor antagonist, 4-DAMP, and binding to Galphai3 antibody
      was inhibited by the m2 receptor antagonist, N,N'-bis[6[[(2
      methoxyphenyl)methyl]amino]hexyl]-1,8-octanediamine tetrahydrochloride
      (methoctramine). The decrease in basal cAMP (35 +/- 5%) induced by ACh in
      dispersed muscle cells was accentuated by 4-DAMP or Gbeta antibody (55 +/- 8 to
      63 +/- 6%). In contrast, methoctramine, pertussis toxin (PTx), or Galphai3
      antibody converted the decrease in cAMP to increase above basal level (+28 +/- 5
      to +32 +/- 6%); the increase in cAMP was abolished by 4-DAMP or Gbeta antibody.
      In muscle cells where only m3 receptors were preserved by selective receptor
      protection, ACh caused only an increase in cAMP that was abolished by 4-DAMP.
      Conversely, in muscle cells where only m2 receptors were preserved, ACh caused an
      accentuated decrease in cAMP that was abolished by methoctramine or PTx. In
      conclusion, m2 receptors in smooth muscle couple to inhibition of adenylyl
      cyclases V/VI via Galphai3, and m3 receptors couple to activation of the enzymes
      via Gbetagammaq/11.

PMID- 9261145
TI  - Coordinate induction of the three neurofilament genes by the Brn-3a transcription
      factor.
AB  - The POU domain transcription factor Brn-3a is able to stimulate neurite outgrowth
      when overexpressed in the neuronal ND7 cell line, whereas the closely related Brn
      3b factor does not have this effect. We show that Brn-3a overexpression also
      enhances the expression of the three neurofilament genes at both the mRNA and
      protein levels, whereas Brn-3b overexpression has no effect. In addition Brn-3a
      activates the three neurofilament gene promoters in co-transfection assays in
      both neuronal and non-neuronal cells. As observed for enhanced neurite outgrowth,
      the stimulation of neurofilament gene expression and activation of the
      neurofilament gene promoters is observed with the isolated POU domain of Brn-3a.
      A single amino acid change in the POU homeodomain of Brn-3a to the equivalent
      amino acid in Brn-3b abolishes its ability to activate the neurofilament
      promoters, whereas the reciprocal change converts Brn-3b to an activator of these
      promoters.

PMID- 9261146
TI  - Critical cytoplasmic domains of human interleukin-9 receptor alpha chain in
      interleukin-9-mediated cell proliferation and signal transduction.
AB  - Interleukin-9 receptor (IL-9R) complex consists of a ligand-specific alpha chain
      and IL-2R gamma chain. In this study, two regions in the cytoplasmic domain of
      human IL-9Ralpha were found to be important for IL-9-mediated cell growth. A
      membrane-proximal region that contains the BOX1 consensus sequence is required
      for IL-9-induced cell proliferation and tyrosine phosphorylation of Janus kinases
      (JAKs). Deletion of this region or internal deletion of the BOX1 motif abrogated
      IL-9-induced cell proliferation and signal transduction. However, substitution of
      the Pro-X-Pro in the BOX1 motif with Ala-X-Ala failed to abolish IL-9-induced
      cell proliferation but decreased IL-9-mediated tyrosine phosphorylation of JAK
      kinases, insulin receptor substrate-2, and signal transducer and activator of
      transcription 3 (STAT3) and expression of c-myc and junB. Another important
      region is downstream of the BOX1 motif and contains a STAT3 binding motif YLPQ.
      Deletion of this region significantly impaired IL-9-induced cell growth,
      activation of JAK kinases, insulin receptor substrate-2, and STAT3 and expression
      of early response genes. A point mutation changing YLPQ into YLPA greatly reduced
      IL-9-induced activation of STAT3 and expression of c-myc but did not affect cell
      proliferation. These results suggest that cooperation or cross-talk of signaling
      molecules associated with different domains of IL-9Ralpha other than STAT3 is
      essential for IL-9-mediated cell growth.

PMID- 9261147
TI  - An RGD to LDV motif conversion within the disintegrin kistrin generates an
      integrin antagonist that retains potency but exhibits altered receptor
      specificity. Evidence for a functional equivalence of acidic integrin-binding
      motifs.
AB  - Integrin ligands almost invariably employ a variant of either the RGD or LDV
      motif as a key element of their receptor recognition site. These short acidic
      peptide sequences collaborate with specific nonhomologous flanking residues and
      spatially separate "synergy" sequences to determine receptor binding specificity.
      Although the consensus sequences for RGD and LDV motifs are quite different,
      their common use suggests that they might share a critical role in receptor
      ligand engagement. To date, the effects of interconversion of the two motifs
      within a natural protein framework have not been tested; however, in this study,
      we have converted the natural RGD site found in the snake venom disintegrin
      kistrin into an LDV motif and examined the effects of the change on the
      specificity of integrin recognition and on disintegrin potency. While an
      assessment of receptor binding using cell adhesion and purified integrin solid
      phase assays demonstrated recognition of recombinant RGD kistrin by alphaVbeta3
      and alpha5beta1, a series of LDV kistrin chimeras did not bind to these
      integrins, but instead were recognized specifically by alpha4beta1. The minimal
      change to elicit this distinct switch in receptor specificity was found to
      involve alteration of only three residues within kistrin. Alanine scanning
      mutagenesis was used to provide further information on the functional
      contribution of the three residues. More important, the LDV kistrin chimeras also
      retained much of the characteristic potency of RGD kistrin, indicating that the
      kistrin scaffold is optimized for presentation of both RGD and LDV sequences.
      These findings provide evidence for similarities in motif pharmacophore and
      reinforce the hypothesis that RGD and LDV sites have an equivalent functional
      role in receptor binding. They also demonstrate the potential for other
      disintegrin-containing proteins, perhaps from the ADAM family, to employ LDV
      sequences for integrin binding.

PMID- 9261148
TI  - Lewis X biosynthesis in Helicobacter pylori. Molecular cloning of an alpha(1,3)
      fucosyltransferase gene.
AB  - The lipopolysaccharide of certain strains of Helicobacter pylori was recently
      shown to contain the Lewis X (Lex) trisaccharide (Galbeta-1, 4-(Fucalpha(1,3))
      GlcNAc). Lex is an oncofetal antigen which appears on human gastric epithelium,
      and its mimicry by carbohydrate structures on the surface of H. pylori may play
      an important part in the interaction of this pathogen with its host. Potential
      roles for bacterial Lex in mucosal adhesion, immune evasion, and autoantibody
      induction have been proposed (Moran, A. P., Prendergast, M. M., and Appelmelk, B.
      J. (1996) FEMS Immunol. Med. Microbiol. 16, 105-115). In mammals, the final step
      of Lex biosynthesis is the alpha(1,3)-fucosylation of GlcNAc in a terminal
      Galbeta(1-->4)GlcNAc unit, and a corresponding GDP-fucose:N-acetylglucosaminyl
      alpha(1,3) fucosyltransferase (alpha(1,3)-Fuc-T) activity was recently discovered
      in H. pylori extracts. We used part of a human alpha(1, 3)-Fuc-T amino acid
      sequence to search an H. pylori genomic data base for related sequences. Using a
      probe based upon weakly matching data base sequences, we retrieved clones from a
      plasmid library of H. pylori DNA. DNA sequence analysis of the library clones
      revealed a gene which we have named fucT, encoding a protein with localized
      homology to the human alpha(1,3)-Fuc-Ts. We have demonstrated that fucT encodes
      an active Fuc-T enzyme by expressing the gene in Escherichia coli. The
      recombinant enzyme shows a strong preference for type 2 (e.g. LacNAc) over type 1
      (e.g. lacto-N-biose) acceptors in vitro. Certain residues in a short segment of
      the H. pylori protein are completely conserved throughout the alpha(1,3)-Fuc-T
      family, defining an alpha(1,3)-Fuc-T motif which may be of use in identifying new
      fucosyltransferase genes.

PMID- 9261149
TI  - Cloning and heterologous expression of an alpha1,3-fucosyltransferase gene from
      the gastric pathogen Helicobacter pylori.
AB  - Helicobacter pylori is an important human pathogen which causes both gastric and
      duodenal ulcers and is also associated with gastric cancer and lymphoma. This
      microorganism has been shown to express cell surface glycoconjugates including
      Lewis X (Lex) and Lewis Y. These bacterial oligosaccharides are structurally
      similar to tumor-associated carbohydrate antigens found in mammals. In this
      study, we report the cloning of a novel alpha1,3-fucosyltransferase gene (HpfucT)
      involved in the biosynthesis of Lex within H. pylori. The deduced amino acid
      sequence of HpfucT consists of 478 residues with the calculated molecular mass of
      56,194 daltons, which is approximately 100 amino acids longer than known
      mammalian alpha1,3/1,4-fucosyltransferases. The approximately 52-kDa protein
      encoded by HpfucT was expressed in Escherichia coli CSRDE3 cells and gave rise to
      alpha1,3-fucosyltransferase activity but neither alpha1,4-fucosyltransferase nor
      alpha1,2-fucosyltransferase activity as characterized by radiochemical assays and
      capillary zone electrophoresis. Truncation of the C-terminal 100 amino acids of
      HpFuc-T abolished the enzyme activity. An approximately 72-amino acid region of
      HpFuc-T exhibits significant sequence identity (40-45%) with the highly conserved
      C-terminal catalytic domain among known mammalian and chicken alpha1,3
      fucosyltransferases. These lines of evidence indicate that the HpFuc-T represents
      the bacterial alpha1,3-fucosyltransferase. In addition, several structural
      features unique to HpFuc-T, including 10 direct repeats of seven amino acids and
      the lack of the transmembrane segment typical for known eukaryotic alpha1,3
      fucosyltransferases, were revealed. Notably, the repeat region contains a leucine
      zipper motif previously demonstrated to be responsible for dimerization of
      various basic region-leucine zipper proteins, suggesting that the HpFuc-T protein
      could form dimers.

PMID- 9261151
TI  - Mechanism of homophilic binding mediated by ninjurin, a novel widely expressed
      adhesion molecule.
AB  - Ninjurin is a novel protein that is up-regulated after nerve injury both in
      dorsal root ganglion (DRG) neurons and in Schwann cells. We previously reported
      that ninjurin demonstrates properties of a homophilic adhesion molecule and
      promotes neurite outgrowth from primary cultured DRG neurons. We have now found
      that ninjurin is widely expressed in both adult and embryonic tissues, primarily
      in those of epithelial origin. Aggregation assays were used to demonstrate that
      ninjurin-mediated adhesion requires divalent cations and is an energy-dependent
      process. The critical domain for ninjurin-mediated homophilic adhesion was
      localized to an 11-residue region (between Pro26 and Asn37) by mutagenesis and by
      employing synthetic oligopeptides as competitive inhibitors of ninjurin-mediated
      adhesion. Of particular importance are the Trp residue at position 29 and the 3
      arginines in the region. Furthermore, we show that the peptide which inhibits
      aggregation of Jurkat cells expressing ninjurin is also capable of blocking the
      ability of ninjurin to promote neurite extension from DRG neurons. Using FISH
      analysis, the ninjurin gene was localized to human chromosome 9q22. Several
      genetic diseases of unknown etiology have been mapped to this region, including
      hereditary sensory neuropathy type 1, self-healing squamous epithelioma, split
      hand/foot deformity type 1, and familial dilated cardiomyopathy.

PMID- 9261150
TI  - Proteolytic activity of the ATP-dependent protease HslVU can be uncoupled from
      ATP hydrolysis.
AB  - HslVU is a new Escherichia coli ATP-dependent protease composed of two multimeric
      complexes: the HslU ATPase and the HslV peptidase. Prior studies indicated that
      HslVU requires ATP hydrolysis for the cleavage of peptides and proteins. We show
      here that ATP concentrations that activate hydrolysis of benzyloxycarbonyl-Gly
      Gly-Leu-7-amido-4-methylcoumarin are 50-100 fold lower than those necessary for
      degradation of proteins (e.g. casein). Also, the nonhydrolyzable analogs of ATP,
      5'-adenylyl beta, gamma-imidodiphosphate (AMP-PNP) and adenosine 5'-(alpha, beta
      methylene)triphosphate, can support peptide hydrolysis, but only after an initial
      time lag not seen with ATP. This delay decreased at higher temperatures and with
      higher HslU or HslV concentrations and was eliminated by preincubation of HslU
      and HslV together. Thus, ATP hydrolysis accelerates the association of HslU and
      HslV, which occurs slowly with the nonhydrolyzable analog. The addition of KCl
      stimulated 4-6-fold the peptidase activity with AMP-PNP present and eliminated
      the time lag, but KCl had no stimulatory effect with ATP. NH4+ and Cs+ had
      similar effects as K+, but Na+ and Li+ were ineffective. AMP-PNP by itself
      supported hydrolysis of casein and other polypeptides only 20% as well as ATP,
      but in the presence of K+, Cs+, or NH4+, AMP-PNP activated casein degradation
      even better than ATP, although it was not hydrolyzed. In addition, MgCl2, MnCl2,
      and CaCl2 allowed some peptidase and caseinase activity in the absence of any
      nucleotide. However, Mn2+ and Ca2+, unlike Mg2+, abolished ATP hydrolysis and
      prevented further activation by ATP or AMP-PNP. These findings indicate that ATP
      binding to a high affinity site triggers the formation of an active state capable
      of peptide cleavage, although ATP hydrolysis facilitates this process. Rapid
      degradation of proteins requires a distinct state of the enzyme, which is
      normally reached through ATP hydrolysis at low affinity sites. However, AMP-PNP
      binding together with K+ can induce a form of HslVU that degrades proteins
      without energy consumption.

PMID- 9261152
TI  - Crystal structure of murine/human Ubc9 provides insight into the variability of
      the ubiquitin-conjugating system.
AB  - Murine/human ubiquitin-conjugating enzyme Ubc9 is a functional homolog of
      Saccharomyces cerevisiae Ubc9 that is essential for the viability of yeast cells
      with a specific role in the G2-M transition of the cell cycle. The structure of
      recombinant mammalian Ubc9 has been determined from two crystal forms at 2.0 A
      resolution. Like Arabidopsis thaliana Ubc1 and S. cerevisiae Ubc4, murine/human
      Ubc9 was crystallized as a monomer, suggesting that previously reported hetero-
      and homo-interactions among Ubcs may be relatively weak or indirect. Compared
      with the known crystal structures of Ubc1 and Ubc4, which regulate different
      cellular processes, Ubc9 has a 5-residue insertion that forms a very exposed
      tight beta-hairpin and a 2-residue insertion that forms a bulge in a loop close
      to the active site. Mammalian Ubc9 also possesses a distinct electrostatic
      potential distribution that may provide possible clues to its remarkable ability
      to interact with other proteins. The 2-residue insertion and other sequence and
      structural heterogeneity observed at the catalytic site suggest that different
      Ubcs may utilize catalytic mechanisms of varying efficiency and substrate
      specificity.

PMID- 9261153
TI  - Implication of mitochondrial hydrogen peroxide generation in ceramide-induced
      apoptosis.
AB  - The key events implicated in ceramide-triggered apoptosis remain unknown. In this
      study we show that 25 microM C6-ceramide induced significant H2O2 production
      within 60 min, which increased up to 180 min in human myeloid leukemia U937
      cells. Inactive analogue dihydro-C6-ceramide had no effect. Furthermore, no H2O2
      production was observed in C6-ceramide-treated U937 rho degrees cells, which are
      mitochondrial respiration-deficient. We also present evidence that ceramide
      induced activation of the transcription factors NF-kappaB and AP-1 is mediated by
      mitochondrial derived reactive oxygen species. Both H2O2 production,
      transcription factor activation as well as apoptosis could be inhibited by
      rotenone and thenoyltrifluoroacetone (specific mitochondrial complexes I and II
      inhibitors) and antioxidants, N-acetylcysteine and pyrrolidine dithiocarbamate.
      These effects could be potentiated by antimycin A (specific complex III
      mitochondrial inhibitor). H2O2 production was also inhibitable by ruthenium red,
      suggesting a role of mitochondrial calcium homeostasis alterations in ceramide
      induced oxidative stress. Finally, C6-ceramide had no influence on mitochondrial
      membrane potential within the first 6 h. Altogether, our study points to reactive
      oxygen species, generated at the ubiquinone site of the mitochondrial respiratory
      chain, as an early major mediator in ceramide-induced apoptosis.

PMID- 9261154
TI  - Role of an RNA-binding protein in import of tRNA into Leishmania mitochondria.
AB  - Nuclear-encoded cytoplasmic tRNAs are imported into the mitochondria of
      kinetoplastid protozoa by an unknown mechanism. In a Leishmania in organello
      system, ATP-dependent import of a cloned, unspliced tRNATyr(GUA) transcript was
      demonstrated by protection from ribonuclease, whereas import of a tRNAGln(CUG)
      transcript was much less efficient. Specific binding of tRNATyr to two
      mitochondrial surface proteins of 15 and 22 kilodaltons was observed. Tubulin
      antisense-binding protein (TAB), the 15-kilodaton species, was purified to
      apparent homogeneity by RNA affinity chromatography. TAB forms stable complexes
      with the D stem-loop region of tRNATyr. Immunocytochemical and cell fractionation
      experiments, combined with limited proteolysis, suggested the association of TAB
      with the outer mitochondrial membrane. Importantly, anti-TAB antibody
      specifically inhibited binding as well as import of tRNATyr and of a synthetic
      structural homolog. These results support the role of TAB as a membrane-bound
      receptor or carrier for RNA import into Leishmania mitochondria.

PMID- 9261155
TI  - A novel 160-kDa phosphotyrosine protein in insulin-treated embryonic kidney cells
      is a new member of the insulin receptor substrate family.
AB  - We have previously identified a 160-kDa protein in human embryonic kidney (HEK)
      293 cells that undergoes rapid tyrosine phosphorylation in response to insulin
      (PY160) (Kuhne, M. R., Zhao, Z., and Lienhard, G. E. (1995) Biochem. Biophys.
      Res. Commun. 211, 190-197). The phosphotyrosine form of PY160 was purified from
      insulin-treated HEK 293 cells by anti-phosphotyrosine immunoaffinity
      chromatography, the sequences of peptides determined, and its cDNA cloned. The
      PY160 cDNA encodes a 1257-amino acid protein that contains, in order from its N
      terminus, a pleckstrin homology (PH) domain, a phosphotyrosine binding (PTB)
      domain, and, spread over the C-terminal portion, 12 potential tyrosine
      phosphorylation sites. Several of these sites are in motifs expected to bind
      specific SH2 domain-containing proteins: YXXM (7 sites), phosphatidylinositol 3
      kinase; YVNM (1 site), Grb-2; and YIEV (1 site), either the protein-tyrosine
      phosphatase SHP-2 or phospholipase Cgamma. Furthermore, the PH and PTB domains
      are highly homologous (at least 40% identical) to those found in insulin receptor
      substrates 1, 2, and 3 (IRS-1, IRS-2, and IRS-3). Thus, PY160 is a new member of
      the IRS family, which we have designated IRS-4.

PMID- 9261156
TI  - Site-directed mutagenesis and characterization of uracil-DNA glycosylase
      inhibitor protein. Role of specific carboxylic amino acids in complex formation
      with Escherichia coli uracil-DNA glycosylase.
AB  - Bacteriophage PBS2 uracil-DNA glycosylase inhibitor (Ugi) protein inactivates
      uracil-DNA glycosylase (Ung) by acting as a DNA mimic to bind Ung in an
      irreversible complex. Seven mutant Ugi proteins (E20I, E27A, E28L, E30L, E31L,
      D61G, and E78V) were created to assess the role of various negatively charged
      residues in the binding mechanism. Each mutant Ugi protein was purified and
      characterized with respect to inhibitor activity and Ung binding properties
      relative to the wild type Ugi. Analysis of the Ugi protein solution structures by
      nuclear magnetic resonance indicated that the mutant Ugi proteins were folded
      into the same general conformation as wild type Ugi. All seven of the Ugi
      proteins were capable of forming a Ung.Ugi complex but varied considerably in
      their individual ability to inhibit Ung activity. Like the wild type Ugi, five of
      the mutants formed an irreversible complex with Ung; however, the binding of Ugi
      E20I and E28L to Ung was shown to be reversible. The tertiary structure of
      [13C,15N]Ugi in complex with Ung was determined by solution state multi
      dimensional nuclear magnetic resonance and compared with the unbound Ugi
      structure. Structural and functional analysis of these proteins have elucidated
      the two-step mechanism involved in Ung.Ugi association and irreversible complex
      formation.

PMID- 9261157
TI  - Decreased nitric-oxide synthase activity causes impaired endothelium-dependent
      relaxation in the postischemic heart.
AB  - Endothelial nitric-oxide synthase (eNOS) is an important regulator of endothelial
      function and vascular tone in biological tissues. While endothelial dysfunction
      occurs following ischemia and has been attributed to altered NO. formation, the
      biochemical basis for this dysfunction is unknown. Therefore, studies were
      performed to determine the effects of myocardial ischemia and reperfusion on eNOS
      in isolated rat hearts subjected to periods of global ischemia or ischemia
      followed by reperfusion. eNOS activity was assayed by L-[14C]arginine to L
      [14C]citrulline conversion and alterations in the amount and distribution of eNOS
      determined by Western blotting and immunohistochemistry. While activity was
      preserved after 30 min of ischemia with a value of 1.1 +/- 0.1 pmol x min-1 x mg
      of protein-1, it decreased by 77% after 60 min and became nearly undetectable
      after 120 min. Reperfusion resulted in only a partial restoration of activity.
      The decline in activity with ischemia was due, in part, to a loss of eNOS
      protein. Hemodynamic studies showed that the onset of impaired vascular
      reactivity paralleled the loss of functional eNOS. Subjecting isolated eNOS to
      conditions of acidosis, which occur during ischemia, followed by restoration of
      pH as occurs on reperfusion, caused a combination of reversible and irreversible
      loss of activity similar to that seen in ischemic and reperfused hearts. Thus,
      loss of endothelial function following ischemia is paralleled by a loss of eNOS
      activity due to a combination of pH-dependent denaturation and proteolysis.

PMID- 9261158
TI  - A synthetic peptide corresponding to the GLUT4 C-terminal cytoplasmic domain
      causes insulin-like glucose transport stimulation and GLUT4 recruitment in rat
      adipocytes.
AB  - In rat epididymal adipocytes, practically all of the major glucose transporter
      isoform GLUT4 is constitutively sequestered in intracellular membranes and moves
      to the plasma membrane in response to insulin, whereas about half of GLUT1, the
      minor isoform, is constitutively functional at the plasma membrane and thus less
      affected by insulin. Transfection studies using cells whose glucose transport is
      normally not regulated by insulin have suggested that the C-terminal cytoplasmic
      domain of GLUT4 is responsible for its constitutive intracellular sequestration.
      To test if this was also the case in a classical insulin target cell, we
      introduced synthetic peptides corresponding to the C-terminal cytoplasmic domain
      of GLUT4 and GLUT1 (GLUT4C and GLUT1C, respectively) into rat adipocytes and
      studied their effects on the glucose transport activity and the steady state
      GLUT4 and GLUT1 distribution between the plasma membrane and intracellular
      membranes in host cells. GLUT4C introduced into basal adipocytes caused a large
      (up to 4.5-fold) and dose-dependent increase in the plasma membrane GLUT4, with a
      proportional reduction in microsomal GLUT4, without affecting GLUT1 distribution.
      GLUT4C incorporation also caused a large (up to 3-fold) dose-dependent
      stimulation of 3-O-methyl D-glucose (3OMG) flux in host cells. GLUT4C caused
      little if any GLUT4 or GLUT1 redistribution and changes in 3OMG flux in insulin
      stimulated adipocytes. GLUT1C, on the other hand, did not affect GLUT1 or GLUT4
      targeting and 3OMG flux in host cells. These findings not only underscore the
      importance of the C-terminal cytoplasmic domain of GLUT4 in its constitutive
      intracellular sequestration in a classical insulin target cell but also suggest
      the existence of a regulatory protein in adipocytes that interacts with GLUT4 at
      its cytoplasmic domain, thus participating in the constitutive intracellular
      sequestration of GLUT4.

PMID- 9261159
TI  - Murine A-myb gene encodes a transcription factor, which cooperates with Ets-2 and
      exhibits distinctive biochemical and biological activities from c-myb.
AB  - The myb gene family consists of three members, named A-, B-, and c-myb, which
      encode nuclear proteins that bind to DNA and function as regulators of
      transcription. Our results show that murine A-myb is a poor transactivator of
      transcription compared with murine c-myb. Deletion of the COOH-terminal domain of
      A-Myb, or co-expression with Ets-2 resulted in increased transactivation
      potential. While ectopic overexpression of c-myb in 32Dcl3 cells results in a
      block to the ability of these cells to undergo terminal differentiation resulting
      in indefinite growth in granulocyte-colony-stimulating factor (G-CSF), similar
      overexpression of A-myb results in growth arrest and concomitant terminal
      differentiation of 32D cells into granulocytes. Co-expression of A-myb and ets-2
      in these cells results in the restoration of the proliferative activity of the
      cells in G-CSF, but fails to induce a block to G-CSF-induced terminal
      differentiation. However, overexpression of the COOH-terminal deletion mutant of
      A-myb results in a block to G-CSF-induced differentiation of 32D cells,
      suggesting that the distinctive biological phenotypes produced by A-myb and c-myb
      genes are mediated by their COOH-terminal domains.

PMID- 9261160
TI  - Identification of a motif associated with the lactogenic actions of human growth
      hormone.
AB  - Human growth hormone (hGH) stimulates somatogenic and lactogenic actions through
      the GH and prolactin (PRL) receptors, respectively. In contrast, non-primate GHs
      stimulate only somatotropic action. Phe44, of the human GH sequence is present in
      all hormones stimulating lactogenic action and absent in all hormones stimulating
      only somatotropic action. We speculate that the presence of Phe44 is a feature
      necessary for specifying lactogenic activity. In this report, the role of Phe44
      was investigated by its deletion or substitution with alanine or leucine.
      Deletion of Phe44 or substitution with leucine did not significantly change the
      structure of hGH as determined by circular dichroism, absorbance, and
      fluorescence spectroscopies. In contrast, substitution of alanine perturbed the
      structure. Deletion of Phe44 reduced binding affinity for the lactogenic
      receptor, resulting in a reduced activation. Substitution with either alanine or
      leucine partially restored lactogenic receptor binding affinity, which correlated
      with the hormones' activity in the Nb2 rat lymphoma cells. All the recombinant
      hGHs had similar somatotropic activities in FDC-P1 cells transfected with the hGH
      receptor. These data indicate that the hydrophobic side chain of Phe44 is
      required for lactogenic receptor binding and activation but is unnecessary for
      somatotropic action.

PMID- 9261161
TI  - Interaction and regulation of the Caenorhabditis elegans death protease CED-3 by
      CED-4 and CED-9.
AB  - In the nematode Caenorhabditis elegans, three genes, ced-3, ced-4, and ced-9,
      play critical roles in the induction and execution of the death pathway. Genetic
      studies have suggested that ced-9 controls programmed cell death by regulating
      ced-4 and ced-3. However, the mechanism by which CED-9 controls the activities of
      CED-4 and the cysteine protease CED-3, the effector arm of the cell-death
      pathway, remains poorly understood. Immunoprecipitation analysis demonstrates
      that CED-9 forms a multimeric protein complex with CED-4 and CED-3 in vivo.
      Expression of wild-type CED-4 promotes the ability of CED-3 to induce apoptosis
      in mammalian cells, which is inhibited by CED-9. The pro-apoptotic activity of
      CED-4 requires the expression of a functional CED-3 protease. Significantly, loss
      of-function CED-4 mutants are impaired in their ability to promote CED-3-mediated
      apoptosis. Expression of CED-4 enhances the proteolytic activation of CED-3. We
      also show that CED-9 inhibits the formation of p13 and p15, two cleavage products
      of CED-3 associated with its proteolytic activation in vivo. Moreover, CED-9
      inhibits the enzymatic activity of CED-3 promoted by CED-4. Thus, these results
      provide evidence that CED-4 and CED-9 regulate the activity of CED-3 through
      physical interactions, which may provide a molecular basis for the control of
      programmed cell death in C. elegans.

PMID- 9261162
TI  - Tumorigenic transformation of immortalized ECV endothelial cells by
      cyclooxygenase-1 overexpression.
AB  - The cyclooxygenase (Cox) enzyme catalyzes the rate-limiting oxidative and
      peroxidative enzymatic steps in the biosynthesis of prostanoids. Both Cox-1 and 
      2 genes encode the two isoenzymes that carry out similar enzymatic steps.
      Enhanced Cox activity is associated with proliferative diseases such as colon
      cancer. To determine if a cause and effect relationship exists between Cox
      isoenzyme overexpression and tumorigenesis, the human Cox-1 and Cox-2 isoenzymes
      were transfected into ECV immortalized endothelial cells. Although numerous
      clones of Cox-1 expressing cells were obtained, Cox-2 overexpression resulted in
      growth disadvantage and increased cell death. In contrast, Cox-1 overexpressing
      cells expressed high levels of the functional Cox-1 polypeptide in the
      endoplasmic reticulum and the nucleus. In vitro proliferation of these cells was
      reduced compared with vector-transfected ECV cells. Cox-1 overexpression also
      enhanced the tumor necrosis factor-alpha-induced apoptosis of ECV cells 2-fold.
      In contrast to the in vitro behavior, ECV-Cox-1 cells proliferated aggressively
      and formed tumors in athymic "nude" mice, whereas the vector-transfected
      counterparts did not. The growth of Cox-1-induced tumors was not inhibited by
      indomethacin, suggesting a nonprostanoid function of Cox-1. ECV-Cox-1-derived
      tumors were angiosarcoma-like and contained numerous host-derived neovessels.
      These data suggest that Cox-1 overexpression in immortalized ECV endothelial
      cells results in nuclear localization of the polypeptide and tumorigenesis.

PMID- 9261163
TI  - Biochemical characterization of the Wilson disease protein and functional
      expression in the yeast Saccharomyces cerevisiae.
AB  - Wilson disease is a disorder of copper metabolism characterized by hepatic
      cirrhosis and neuronal degeneration due to inherited mutations in a gene encoding
      a putative copper-transporting P-type ATPase. Polyclonal antisera generated
      against the amino terminus of the Wilson protein detected a specific 165-kDa
      protein in HepG2 and CaCo cell lysates. Further analysis revealed that this
      protein is synthesized as a single-chain polypeptide and localized to the trans
      Golgi network under steady state conditions. An increase in the copper
      concentration resulted in the rapid movement of this protein to a cytoplasmic
      vesicular compartment. This copper-specific cellular redistribution of the Wilson
      protein is a reversible process that occurs independent of a new protein
      synthesis. Expression of the wild-type but not mutant Wilson protein in the
      ccc2Delta strain of Saccharomyces cerevisiae restored copper incorporation into
      the multicopper oxidase Fet3p, providing direct evidence of copper transport by
      the Wilson protein. Taken together these data reveal a remarkable evolutionary
      conservation in the cellular mechanisms of copper metabolism and provide a unique
      model for the regulation of copper transport into the secretory pathway of
      eucaryotic cells.

PMID- 9261164
TI  - A new function for the C-terminal zinc finger of the glucocorticoid receptor.
      Repression of RelA transactivation.
AB  - Glucocorticoids inhibit NF-kappaB signaling by interfering with the NF-kappaB
      transcription factor RelA. Previous studies have identified the DNA-binding
      domain (DBD) in the glucocorticoid receptor (GR) as the major region responsible
      for this repressive activity. Using GR mutants with chimeric DBDs the repressive
      function was found to be located in the C-terminal zinc finger. As predicted from
      these results the mineralocorticoid receptor that contains a C-terminal zinc
      finger identical to that of the GR was also able to repress RelA-dependent
      transcription. Mutation of a conserved arginine or a lysine in the second zinc
      finger of the GR DBD (Arg-488 or Lys-490 in the rat GR) abolished the ability of
      GR to inhibit RelA activity. In contrast, C-terminal zinc finger GR mutants with
      mutations in the dimerization box or mutations necessary for full transcriptional
      GR activity were still able to repress RelA-dependent transcription. In addition,
      we found that the steroid analog ZK98299 known to induce GR transrepression of AP
      1 had no inhibitory effect on RelA activity. In summary, these results
      demonstrate that the inhibition of NF-kappaB by glucocorticoids involves two
      critical amino acids in the C-terminal zinc finger of the GR. Furthermore, the
      results from the use of mineralocorticoid receptor and anti-glucocorticoids
      suggest that the mechanisms for GR-mediated repression of NF-kappaB and AP-1 are
      different.

PMID- 9261165
TI  - Peroxisome proliferator activated receptor gamma, CCAAT/enhancer-binding protein
      alpha, and cell cycle status regulate the commitment to adipocyte
      differentiation.
AB  - Terminal differentiation of stem cells is characterized by cessation of cell
      proliferation as well as changes in cell morphology associated with the
      differentiated state. For adipocyte differentiation, independent lines of
      evidence show that the transcription factors peroxisome proliferator activated
      receptor gamma (PPARgamma) and CCAAT/enhancer-binding protein alpha (C/EBPalpha)
      as well as the tumor suppressor retinoblastoma (Rb) protein are essential. How
      these proteins promote adipocyte conversion and how they function cooperatively
      during the differentiation process remain unclear. We have used retinoic acid
      (RA) inhibition of adipogenesis to investigate these issues. RA blocked
      adipogenesis of 3T3-L1 cells induced to differentiate by ectopic expression of
      PPARgamma and C/EBPalpha independently or together. However, under these
      circumstances RA was only effective at preventing adipogenesis when added prior
      to confluence, suggesting that factors involved in regulation of the cell cycle
      might play a role in establishing the commitment state of adipogenesis that is
      insensitive to RA. During differentiation of wild type 3T3 L1 preadipocytes, we
      found that Rb protein is hyperphosphorylated early in adipogenesis, corresponding
      to previously quiescent cells re-entering the cell cycle, and later becomes
      hypophosphorylated. The data suggest that, together with the coexpression of
      PPARgamma and C/EBPalpha, permanent exit from the cell cycle establishes the
      irreversible commitment to adipocyte differentiation.

PMID- 9261167
TI  - Neuronal pentraxin receptor, a novel putative integral membrane pentraxin that
      interacts with neuronal pentraxin 1 and 2 and taipoxin-associated calcium-binding
      protein 49.
AB  - We have identified the first putative integral membrane pentraxin and named it
      neuronal pentraxin receptor (NPR). NPR is enriched by affinity chromatography on
      columns of a snake venom toxin, taipoxin, and columns of the taipoxin-binding
      proteins neuronal pentraxin 1 (NP1), neuronal pentraxin 2 (NP2), and taipoxin
      associated calcium-binding protein 49 (TCBP49). The predominant form of NPR
      contains an putative NH2-terminal transmembrane domain and all forms of NPR are
      glycosylated. NPR has 49 and 48% amino acid identity to NP1 and NP2,
      respectively, and NPR message is expressed in neuronal regions that express NP1
      and NP2. We suggest that NPR, NP1, NP2, and TCBP49 are involved in a pathway
      responsible for the transport of taipoxin into synapses and that this may
      represent a novel neuronal uptake pathway involved in the clearance of synaptic
      debris.

PMID- 9261166
TI  - Blockade of glycosylation promotes acquisition of scrapie-like properties by the
      prion protein in cultured cells.
AB  - The conformational conversion of the prion protein, a sialoglycoprotein
      containing two N-linked oligosaccharide chains, from its normal form (PrPC) to a
      pathogenic form (PrPSc) is the central causative event in prion diseases.
      Although PrPSc can be generated in the absence of glycosylation, there is
      evidence that oligosaccharide chains may modulate the efficiency of the
      conversion process, and may also serve as molecular markers of diverse prion
      strains. In addition, mutational inactivation of one of the N-glycosylation sites
      has recently been associated with a familial spongiform encephalopathy. To
      investigate the role of N-glycans in determining the properties of PrP, we have
      expressed in transfected Chinese hamster ovary cells mouse PrP molecules in which
      N-glycosylation has been blocked either by treatment with the drug tunicamycin,
      or by substitution of alanine for threonine at one or both of the N-X-T consensus
      sites. We report that PrP molecules mutated at Thr182 alone or at both Thr182 and
      Thr198 [corrected] fail to reach the cell surface after synthesis, but that those
      mutated at Thr198 [corrected] or synthesized in the presence of tunicamycin can
      be detected on the plasma membrane. We also find that all three mutant PrPs, and
      to a limited extent wild-type PrP synthesized in the presence of inhibitor,
      acquire biochemical attributes reminiscent of PrPSc. We suggest that the PrP
      molecule has an intrinsic tendency to acquire some PrPSc-like properties, and
      that N-glycan chains protect against this change. However, pathogenic mutations,
      or presumably contact with exogenous prions, are necessary to fully convert the
      protein to a PrPSc state.

PMID- 9261168
TI  - Two-hybrid analysis reveals fundamental differences in direct interactions
      between desmoplakin and cell type-specific intermediate filaments.
AB  - Desmosomes are cell junctions that act as sites of strong intercellular adhesion
      and also serve to anchor the intermediate filament (IF) cytoskeleton to the
      plasma membrane of a variety of cell types. Previous studies demonstrated that
      the COOH terminus of the desmosomal plaque protein, desmoplakin (DP), is required
      for the association of DP with IF networks in cultured cells and that this domain
      interacts directly with type II epidermal keratin polypeptides in vitro. However,
      these studies left open the question of how desmosomes might anchor other IF
      types known to associate with these junctions. In this report we used yeast two
      hybrid and in vitro dot blot assays to further examine the requirements for
      direct interactions between desmoplakin and various IF types. Our results confirm
      the ability of the DP COOH terminus (DPCT) to interact with at least two regions
      of the head domain of the type II epidermal keratin K1 and also demonstrate that
      DPCT can interact with the type III IF family members, vimentin and desmin, as
      well as simple epithelial keratins. Unlike the situation for type II epidermal
      keratins, the interaction between DPCT and simple epithelial keratins appears to
      depend on heterodimerization of the type I and II keratin polypeptides, since
      both are required to detect an interaction. Furthermore, although the interaction
      between DPCT and K1 requires the keratin head domain, deletion of this domain
      from the simple epithelial keratins does not compromise interaction with DPCT.
      The interaction between DPCT and type III or simple epithelial keratins also
      appeared to be less robust than that between DPCT and K1. In the case of K8/K18,
      however, the interaction as assessed by yeast two-hybrid assays increased 9-fold
      when a serine located in a protein kinase A consensus phosphorylation site 23
      residues from the end of DP was altered to a glycine. Taken together, these data
      indicate that DP interacts directly with different IF types in specific ways.

PMID- 9261169
TI  - Alpha-latrotoxin receptor, latrophilin, is a novel member of the secretin family
      of G protein-coupled receptors.
AB  - alpha-Latrotoxin (LTX) stimulates massive exocytosis of synaptic vesicles and may
      help to elucidate the mechanism of regulation of neurosecretion. We have recently
      isolated latrophilin, the synaptic Ca2+-independent LTX receptor. Now we
      demonstrate that latrophilin is a novel member of the secretin family of G
      protein-coupled receptors that are involved in secretion. Northern blot analysis
      shows that latrophilin message is present only in neuronal tissue. Upon
      expression in COS cells, the cloned protein is indistinguishable from brain
      latrophilin and binds LTX with high affinity. Latrophilin physically interacts
      with a Galphao subunit of heterotrimeric G proteins, because the two proteins co
      purify in a two-step affinity chromatography. Interestingly, extracellular domain
      of latrophilin is homologous to olfactomedin, a soluble neuronal protein thought
      to participate in odorant binding. Our findings suggest that latrophilin may bind
      unidentified endogenous ligands and transduce signals into nerve terminals, thus
      implicating G proteins in the control of synaptic vesicle exocytosis.

PMID- 9261170
TI  - Identification and phenotypic analysis of two glyoxalase II encoding genes from
      Saccharomyces cerevisiae, GLO2 and GLO4, and intracellular localization of the
      corresponding proteins.
AB  - We have isolated and characterized two genes coding for the glyoxalase II enzyme
      from Saccharomyces cerevisiae. The coding region of the GLO2 gene corresponds to
      a protein with 274 amino acids and a molecular mass of 31,306 daltons. The open
      reading frame of the GLO4 gene could be translated into a protein with 285 amino
      acids and a molecular mass of 32,325 daltons. The amino acid sequences of the
      deduced proteins are 59.1% identical and show high similarities to the sequence
      of the human glyoxalase II. When grown on either glucose or glycerol as a carbon
      source, a glo2 glo4 double deletion strain contains no glyoxalase II activity at
      all and shows no obvious phenotype during vegetative growth. However, this strain
      showed a similar high sensitivity against exogenous methylglyoxal as compared
      with a glyoxalase I-deficient strain. Whereas the GLO2 gene is expressed on both
      glucose and glycerol, the GLO4 gene is only active on glycerol. The active Glo2p
      protein is localized in the cytoplasm and the active Glo4p in the mitochondrial
      matrix. Heterologous expression of the full-length GLO2 coding region in
      Escherichia coli resulted in an active protein. However, to get an active Glo4p
      protein in E. coli, the putative mitochondrial transit peptide at the N-terminal
      end had to be removed by shortening the 5' end of the GLO4 open reading frame.

PMID- 9261171
TI  - Regulation of protein kinase B in rat adipocytes by insulin, vanadate, and
      peroxovanadate. Membrane translocation in response to peroxovanadate.
AB  - Protein kinase B (PKB) (also referred to as RAC/Akt kinase) has been shown to be
      controlled by various growth factors, including insulin, using cell lines and
      transfected cells. However, information is so far scarce regarding its regulation
      in primary insulin-responsive cells. We have therefore used isolated rat
      adipocytes to examine the mechanisms, including membrane translocation, whereby
      insulin and the insulin-mimicking agents vanadate and peroxovanadate control PKB.
      Stimulation of adipocytes with insulin, vanadate, or peroxovanadate caused
      decreased PKB mobility on sodium dodecyl sulfate-polyacrylamide gels, indicative
      of increased phosphorylation, which correlated with an increase in kinase
      activity detected with the peptide KKRNRTLTK. This peptide was found to detect
      activated PKB selectively in crude cytosol and partially purified cytosol
      fractions from insulin-stimulated adipocytes. The decrease in electrophoretic
      mobility and activation of PKB induced by insulin was reversed both in vitro by
      treatment of the enzyme with alkaline phosphatase and in the intact adipocyte
      upon removal of insulin or addition of the phosphatidylinositol 3-kinase (PI 3
      kinase) inhibitor wortmannin. Significant translocation of PKB to membranes could
      not be demonstrated after insulin stimulation, but peroxovanadate, which appeared
      to activate PI 3-kinase to a higher extent than insulin, induced substantial
      translocation. The translocation was prevented by wortmannin, suggesting that PI
      3-kinase and/or the 3-phosphorylated phosphoinositides generated by PI 3-kinase
      are indeed involved in the membrane targeting of PKB.

PMID- 9261172
TI  - Evaluation of the initiation phase of blood coagulation using ultrasensitive
      assays for serine proteases.
AB  - The initiation phase of enzyme generation in a reconstituted model of the tissue
      factor (TF) pathway to thrombin was evaluated. At 1.25 pM added TF, no thrombin
      generation was observed in the absence of factor V. The substitution of factor Va
      for factor V increased the rate of thrombin generation. Factor X activation
      during the initiation phase was not influenced by the absence of factor VIII or
      thrombin, leading to the conclusion that initially factor Xa is generated
      exclusively by the factor VIIa-TF complex. When thrombin was eliminated from the
      system, no contribution of the factor IXa-factor VIIIa complex to factor X
      activation was observed during the propagation phase. Similarly, factor V
      activation was also not observed in the absence of thrombin, indicating that
      thrombin is the only enzyme responsible for factor V and factor VIII activation.
      Only subnanomolar amounts of factor VII were activated when prothrombin
      activation was almost complete. In the absence of coagulation inhibitors, factor
      XI did not influence thrombin generation initiated by 1.25 pM factor VIIa-TF
      complex. The termination of factor XIa generation by added hirudin in the factor
      XI experiment indicates that factor XI activation occurs exclusively by thrombin.

PMID- 9261173
TI  - High levels of the GTPase Ran/TC4 relieve the requirement for nuclear protein
      transport factor 2.
AB  - The GTPase Ran/TC4 and the 14-kDa protein nuclear transport factor 2 (NTF2) are
      two of the cytosolic factors that mediate nuclear protein import in vertebrates.
      Previous biochemical studies have shown that NTF2 binds directly to the GDP-bound
      form of Ran/TC4 and to proteins of the nuclear pore complex that contain
      phenylalanine-glycine repeats. In the present study we have used molecular
      genetic approaches to study the Saccharomyces cerevisiae homologue of NTF2. The
      scNTF2 gene encodes a protein that is 44% identical to the human protein. We
      found that deletion of the scNTF2 gene is lethal and that repression of NTF2p
      expression by a regulatable promoter results in gross structural distortions of
      the nuclear envelope. In a screen for high copy number suppressors of a scNTF2
      deletion, the only gene we isolated other than scNTF2 itself was GSP1, the S.
      cerevisiae homologue of Ran/TC4. Furthermore, we found that high levels of
      Ran/TC4 can relieve the requirement for NTF2 in a mammalian-permeabilized cell
      assay for nuclear protein import. These data suggest that certain of the nuclear
      protein import functions of NTF2 and Ran/TC4 are closely linked and that NTF2 may
      serve to modulate a transport step involving Ran/TC4.

PMID- 9261174
TI  - The interleukin-1 receptor-associated kinase is degraded by proteasomes following
      its phosphorylation.
AB  - Following interleukin (IL)-1 stimulation, the majority of the cellular
      interleukin-1 receptor-associated kinase (IRAK) translocates to a discrete subset
      of the Type I IL-1 receptor (IL-1R1) in MRC-5 human lung fibroblasts. As the IRAK
      becomes multiphosphorylated, it is degraded by proteasomes at a rate comparable
      to that of the degradation of the phosphorylated IkappaBalpha protein. Proteasome
      inhibitors block the degradation of phosphorylated IRAK and correspondingly
      increase the amount of IL-1R1 that can be coimmunoprecipitated with IRAK. The
      nonspecific kinase inhibitor K-252b blocks IRAK phosphorylation and degradation,
      but does not inhibit IRAK association with the IL-1R1 indicating that
      translocation of IRAK to the IL-1R1 and its phosphorylation are independent
      events. The IL-1 specificity of these effects is indicated by the lack of IRAK
      phosphorylation and degradation by IL-1 in the presence of the IL-1 receptor
      antagonist or by the activation of MRC-5 cells by tumor necrosis factor alpha.
      Long term exposure of MRC-5 cells to IL-1 desensitizes the resynthesized
      IkappaBalpha to IL-1, but not to tumor necrosis factor alpha stimulation, but no
      additional effects on IRAK are seen.

PMID- 9261175
TI  - Association of the T-cell protein tyrosine phosphatase with nuclear import factor
      p97.
AB  - Alternative splicing of the T-cell protein tyrosine phosphatase (TCPTP)
      transcript generates two forms of the enzyme that differ at their extreme C
      termini: a 48-kDa endoplasmic reticulum-associated form and a 45-kDa nuclear
      form. By affinity chromatography, using GST-TCPTP fusion proteins, we have
      isolated three cytoplasmic proteins of 120, 116, and 97 kDa that interact with
      TCPTP. The p120 protein associated with residues 377-415 from the C terminus of
      the 48-kDa form of TCPTP, whereas the recognition site for p97 and p116 was
      mapped to residues 350-381 encompassing the TCPTP nuclear localization sequence
      (NLS). The TCPTP NLS was shown to be bipartite, requiring basic residues 350-358
      (basic cluster I) and 377-381 (basic cluster II), the sites of interaction with
      p97 and p116, for efficient nuclear translocation. The interaction between p97,
      p116, and the TCPTP NLS appeared unique in that these proteins did not form a
      stable interaction with the classical NLS of SV40 large T antigen or the standard
      bipartite NLS of nucleoplasmin. Sequence analysis of p97 identified it as the
      nuclear import factor p97 (importin-beta), which is an essential component of the
      nuclear import machinery. In assays in vitro in permeabilized cells, p97 was
      necessary but not sufficient for optimal nuclear import of TCPTP. We found that
      TCPTP co-immunoprecipitated with the nuclear import factor p97 from cell lysates
      and that purified recombinant p97 and TCPTP interacted directly in vitro. These
      results indicate selectivity in the binding of p97 and p116 to the TCPTP NLS and
      suggest that p97 may mediate events that are distinct from the classical nuclear
      import process. Moreover, these results demonstrate that the C-terminal segment
      of TCPTP contains docking sites for interaction with proteins that may function
      to target the enzyme to defined intracellular locations and in the process
      regulate TCPTP function.

PMID- 9261176
TI  - Purification, characterization, and reconstitution of DNA-dependent RNA
      polymerases from Caulobacter crescentus.
AB  - Cell differentiation in the Caulobacter crescentus cell cycle requires
      differential gene expression that is regulated primarily at the transcriptional
      level. Until now, however, a defined in vitro transcription system for the
      biochemical study of developmentally regulated transcription factors had not been
      available in this bacterium. We report here the purification of C. crescentus RNA
      polymerase holoenzymes and resolution of the core RNA polymerase from holoenzymes
      by chromatography on single-stranded DNA cellulose. The three RNA polymerase
      holoenzymes Esigma54, Esigma32, and Esigma73 were reconstituted exclusively from
      purified C. crescentus core and sigma factors. Reconstituted Esigma54 initiated
      transcription from the sigma54-dependent fljK promoter of C. crescentus in the
      presence of the transcription activator FlbD, and active Esigma32 specifically
      initiated transcription from the sigma32-dependent promoter of the C. crescentus
      heat-shock gene dnaK. For reconstitution of the Esigma73 holoenzyme, we
      overexpressed the C. crescentus rpoD gene in Escherichia coli and purified the
      full-length sigma73 protein. The reconstituted Esigma73 recognized the sigma70
      dependent promoters of the E. coli lacUV5 and neo genes, as well as the sigma73
      dependent housekeeping promoters of the C. crescentus pleC and rsaA genes. The
      ability of the C. crescentus Esigma73 RNA polymerase to recognize E. coli sigma70
      dependent promoters is consistent with relaxed promoter specificity of this
      holoenzyme previously observed in vivo.

PMID- 9261177
TI  - Mutational analysis of the role of the distal histidine and glutamine residues of
      prostaglandin-endoperoxide synthase-2 in peroxidase catalysis, hydroperoxide
      reduction, and cyclooxygenase activation.
AB  - Site-directed mutants of prostaglandin-endoperoxide synthase-2 (PGHS-2) with
      changes in the peroxidase active site were prepared by mutagenesis, expressed in
      Sf-9 cells, and purified to homogeneity. The distal histidine, His193, was
      mutated to alanine and the distal glutamine, Gln189, was changed to asparagine,
      valine, and arginine. The guaiacol peroxidase activities of H193A, Q189V, and
      Q189R were drastically reduced to levels observed in the absence of protein; only
      Q189N retained wild-type PGHS-2 (wtPGHS-2) activity. The mechanism of
      hydroperoxide reduction by the PGHS-2 mutants was investigated using 15
      hydroperoxyeicosatetraenoic acid (15-HPETE), a diagnostic probe of hydroperoxide
      reduction pathways. The hydroperoxide reduction activity of Q189V and Q189R was
      reduced to that of free Fe(III) protoporphyrin IX levels, whereas Q189N catalyzed
      more reduction events than wtPGHS-2. The percentage of two-electron reduction
      events was identical for wtPGHS-2 and Q189N. The number of hydroperoxide
      reductions catalyzed by H193A was reduced to approximately 60% of wtPGHS-2
      activity, but the majority of products were the one-electron reduction products,
      15-KETE and epoxyalcohols. Thus, mutation of the distal histidine to alanine
      leads to a change in the mechanism of hydroperoxide reduction. Reaction of wtPGHS
      2, Q189N, and H193A with varying concentrations of 15-HPETE revealed a change in
      product profile that suggests that 15-HPETE can compete with the reducing
      substrate for oxidation by the peroxidase higher oxidation state, compound I. The
      ability of the PGHS-2 proteins to catalyze two-electron hydroperoxide reduction
      correlated with the activation of cyclooxygenase activity. The reduced ability of
      H193A to catalyze two-electron hydroperoxide reduction resulted in a substantial
      lag phase in the cyclooxygenase assay. The addition of 2-methylimidazole
      chemically reconstituted the two-electron hydroperoxide reduction activity of
      H193A and abolished the cyclooxygenase lag phase. These observations are
      consistent with the involvement of the two-electron oxidized peroxidase
      intermediate, compound I, as the mediator of the activation of the cyclooxygenase
      of PGHS.

PMID- 9261178
TI  - The mouse extracellular signal-regulated kinase 2 gene. Gene structure and
      characterization of the promoter.
AB  - ERK2 (extracellular-signal regulated kinase 2, also known as p42 mitogen
      activated protein kinase) is an integral member of the mitogen-activated protein
      kinase cascade that is crucial for many cellular events such as proliferation and
      differentiation. Here, we determined the genomic organization of the Erk2 gene
      and characterized its promoter. The Erk2 gene spans over 60 kilobases, and the
      coding region is split into eight exons. In the coding region, exon-intron
      organization was exactly conserved between the two mouse genes for ERK2 and ERK1
      except one junction shifted by one nucleotide. Primer extension and S1 nuclease
      analyses identified two major transcription start sites located at -219 and -223
      relative to the translation start site. The 5'-flanking sequence lacked TATA box
      but contained a CCAAT box located approximately 60 base pairs upstream of
      transcription start sites. Sequencing of the 5'-flanking region also revealed
      potential cis-acting elements for multiple transcriptional regulatory factors
      including Sp1, zif268, Ets, CREB, and PuF sites. The promoter activity of the 5'
      flanking region was examined using chloramphenicol acetyltransferase as a
      reporter gene. Transient transfection experiments using Chinese hamster ovary
      cells defined a maximal promoter activity in a 371-base pair region immediately
      upstream of the translation start site. Furthermore, we demonstrated, using mouse
      P19 embryonal carcinoma cells, that this 371-base pair sequence is likely to be
      sufficient to confer the transcriptional activation of the ERK2 promoter during
      the retinoic acid-induced differentiation of P19 cells.

PMID- 9261179
TI  - Characterization of the precursor of prostate-specific antigen. Activation by
      trypsin and by human glandular kallikrein.
AB  - The precursor or zymogen form of prostate-specific antigen (pro-PSA) is composed
      of 244 amino acid residues including an amino-terminal propiece of 7 amino acids.
      Recombinant pro-PSA was expressed in Escherichia coli, isolated from inclusion
      bodies, refolded, and purified. The zymogen was readily activated by trypsin at a
      weight ratio of 50:1 to generate PSA, a serine protease that cleaves the
      chromogenic chymotrypsin substrate 3-carbomethoxypropionyl-L-arginyl-L-prolyl-L
      tyrosine-p-nitroanili ne- HCl (S-2586). In this activation, the amino-terminal
      propiece Ala-Pro-Leu-Ile-Leu-Ser-Arg was released by cleavage at the Arg-Ile
      peptide bond. The recombinant pro-PSA was also activated by recombinant human
      glandular kallikrein, another prostate-specific serine protease, as well as by a
      partially purified protease(s) from seminal plasma. The recombinant PSA was
      inhibited by alpha1-antichymotrypsin, forming an equimolar complex with a
      molecular mass of approximately 100 kDa. The recombinant PSA failed to activate
      single chain urokinase-type plasminogen activator, in contrast to the recombinant
      hK2, which readily activated single chain urokinase-type plasminogen activator.
      These results indicate that pro-PSA is converted to an active serine protease by
      minor proteolysis analogous to the activation of many of the proteases present in
      blood, pancreas, and other tissues. Furthermore, PSA is probably generated by a
      cascade system involving a series of precursor proteins. These proteins may
      interact in a stepwise manner similar to the generation of plasmin during
      fibrinolysis or thrombin during blood coagulation.

PMID- 9261180
TI  - Palmitoylation of human endothelinB. Its critical role in G protein coupling and
      a differential requirement for the cytoplasmic tail by G protein subtypes.
AB  - By site-directed mutagenesis, three cysteine residues (amino acids 402, 403, and
      405) in the carboxyl terminus of human endothelinB (ETB) were identified as
      potential palmitoylation sites. Substitutions of all of the three cysteine
      residues with serine gave an unpalmitoylated mutant, C2S/C3S/C5S. When expressed
      in Chinese hamster ovary cells, C2S/C3S/C5S was localized on the cell surface,
      retained high affinities to ET-1 and ET-3, and was rapidly internalized when
      bound to the ligand. However, unlike the wild-type ETB, C2S/C3S/C5S transmitted
      neither an inhibitory effect on adenylate cyclase nor a stimulatory effect on
      phospholipase C, indicating a critical role of palmitoylation in the coupling
      with G proteins, regardless of the G protein subtypes. Truncation of the carboxyl
      terminus including Cys403/Cys405 gave a deletion mutant Delta403 that was
      palmitoylated on Cys402 and lacked the carboxyl terminus downstream to the
      palmitoylation site. Delta403 did transmit a stimulatory effect on phospholipase
      C via a pertussis toxin-insensitive G protein but it failed to transmit an
      inhibitory effect on adenylate cyclase. These results indicated a differential
      requirement for the carboxyl terminus downstream to the palmitoylation site in
      the coupling with G protein subtypes, i.e. it is required for the coupling with
      Gi but not for that with Gq.

PMID- 9261181
TI  - Transcription factor GATA-3 is differentially expressed in murine Th1 and Th2
      cells and controls Th2-specific expression of the interleukin-5 gene.
AB  - Interleukin-5 (IL-5), which is produced by CD4(+) T helper 2 (Th2) cells, but not
      by Th1 cells, plays a key role in the development of eosinophilia in asthma.
      Despite increasing evidence that the outcome of many diseases is determined by
      the ratio of the two subsets of CD4(+) T helper cells, Th1 and Th2, the molecular
      basis for Th1- and Th2-specific gene expression remains to be elucidated. We
      previously established a critical role for the transcription factor GATA-3 in IL
      5 promoter activation in EL-4 cells, which express both Th1- and Th2-type
      cytokines. Our studies reported here demonstrate that GATA-3 is critical for
      expression of the IL-5 gene in bona fide Th2 cells. Whereas mutations in the GATA
      3 site abolished antigen- or cAMP-stimulated IL-5 promoter activation in Th2
      cells, ectopic expression of GATA-3 in Th1 cells or in a non-lymphoid, non-IL-5
      producing cell line activated the IL-5 promoter. During the differentiation of
      naive CD4(+) T cells isolated from T cell receptor transgenic mice, GATA-3 gene
      expression was up-regulated in developing Th2 cells, but was down-regulated in
      Th1 cells, and antigen- or cAMP-activated Th2 cells (but not Th1 cells) expressed
      the GATA-3 protein. Thus, GATA-3 may play an important role in the balance
      between Th1 and Th2 subsets in immune responses. Inhibition of GATA-3 activity
      has therapeutic potential in the treatment of asthma and other hypereosinophilic
      diseases.

PMID- 9261182
TI  - In vitro synthesis of the iron-molybdenum cofactor and maturation of the nif
      encoded apodinitrogenase. Effect of substitution of VNFH for NIFH.
AB  - NIFH (the nifH gene product) has several functions in the nitrogenase enzyme
      system. In addition to reducing dinitrogenase during nitrogenase turnover, NIFH
      functions in the biosynthesis of the iron-molybdenum cofactor (FeMo-co), and in
      the processing of alpha2beta2 apodinitrogenase 1 (a catalytically inactive form
      of dinitrogenase 1 that lacks the FeMo-co) to the FeMo-co-activatable
      alpha2beta2gamma2 form. The molybdenum-independent nitrogenase 2 (vnf-encoded)
      has a distinct dinitrogenase reductase protein, VNFH. We investigated the ability
      of VNFH to function in the in vitro biosynthesis of FeMo-co and in the maturation
      of apodinitrogenase 1. VNFH can replace NIFH in both the biosynthesis of FeMo-co
      and in the maturation of apodinitrogenase 1. These results suggest that the
      dinitrogenase reductase proteins do not specify the heterometal incorporated into
      the cofactors of the respective nitrogenase enzymes. The specificity for the
      incorporation of molybdenum into FeMo-co was also examined using the in vitro
      FeMo-co synthesis assay system.

PMID- 9261183
TI  - Angiotensin II increases macrophage-mediated modification of low density
      lipoprotein via a lipoxygenase-dependent pathway.
AB  - The molecular and cellular mechanisms by which hypertension enhances
      atherosclerosis are poorly understood. Angiotensin II (Ang II) has been
      implicated in the regulation of cellular lipoxygenases (LO), which are thought to
      play a role in atherogenesis by inducing oxidative modification of low density
      lipoprotein (LDL). We sought to test the hypothesis that Ang II would stimulate
      murine macrophage LO activity (which has both 12- and 15-LO activity).
      Competitive binding studies revealed the presence of Ang II AT1 receptors on
      mouse peritoneal macrophages (MPM) and J-774 cells, but not on the RAW cell line.
      Valsartan, a specific AT1 receptor antagonist inhibited Ang II binding, whereas
      PD 123319, an AT2 receptor antagonist did not. Incubation of MPM or J-774 cells
      with Ang II (10 pM to 1 microM) for 24 h led to a 2.5-3.5-fold increase in LO
      activity, measured as generated 13-HODE or 12(S)-HETE. This stimulation was
      inhibited by valsartan, but not by PD 123319. In contrast, Ang II did not
      stimulate LO activity in RAW macrophages. Semiquantitative reverse transcriptase
      polymerase chain reaction showed a 2-3-fold increase in LO mRNA in MPM, but not
      in RAW cells after treatment with Ang II. Ang II also induced an increase in 12
      LO protein. In addition, pretreatment of J-774 cells with Ang II increased in a
      dose-dependent manner the ability of the cells to modify LDL, resulting in
      greater chemotactic activity for monocytes, typical of minimally modified LDL.
      This stimulation was inhibited by AT1 receptor blockade. In summary, these data
      suggest that Ang II increases macrophage LO activity via AT1 receptor-mediated
      mechanisms and this further increases the ability of the cells to generate
      minimally oxidized LDL. These studies provide a link between hypertension and the
      associated increased atherosclerosis observed in hypertensive patients.

PMID- 9261184
TI  - Cooperative binding of NF-Y and Sp1 at the DNase I-hypersensitive site, fatty
      acid synthase insulin-responsive element 1, located at -500 in the rat fatty acid
      synthase promoter.
AB  - In vitro DNase I footprint analysis of the rat fatty acid synthase (FAS) promoter
      from -568 to -468 revealed four protein binding sites: A, B, and C boxes and the
      FAS insulin-responsive element 1 (FIRE1). As demonstrated by gel mobility shift
      analysis and supershift experiments, FIRE1, located between -516 and -498, is
      responsible for binding NF-Y. The C box located downstream of FIRE1 was shown by
      in vitro footprinting to be a Sp1 binding site, and furthermore, competition with
      Sp1 also abolished FIRE1 binding. Since the half-life of the Sp1.NF-Y.DNA complex
      is significantly longer than the half-lives of the Sp1.DNA or NF-Y.DNA complexes,
      the two transcription factors are deemed to bind cooperatively in the FAS
      promoter at -500. It is unusual that NF-Y binds at this distance from the start
      site of transcription. NF-Y binding sites are found in the promoters of at least
      three other FAS genes, viz. goose, chicken, and man. A second NF-Y binding site
      is located in the FAS promoter at the more usual position of -103 to -87, and it
      too has a neighboring Sp1 site. CTF/NF-1 competes for proteins binding to the B
      box. The A box binds Sp1 and contains a 12/13 match of the inverted repeat
      sequence responsible for binding the nuclear factor EF-C/RFX-1 in the enhancer
      regions of hepatitis B virus and the major histocompatibility complex class II
      antigen promoter. The same relative positions of NF-Y and Sp1 binding sites in
      the promoters of FAS genes of goose, rat, chicken, and man emphasize the
      involvement of these transcription factors in the diet and hormonal regulation of
      FAS.

PMID- 9261186
TI  - Structural elucidation of oxygenated storage lipids in cucumber cotyledons.
      Implication of lipid body lipoxygenase in lipid mobilization during germination.
AB  - At early stages of germination, a special lipoxygenase is expressed in cotyledons
      of cucumber and several other plants. This enzyme is localized at the lipid
      storage organelles and oxygenates their storage triacylglycerols. We have
      isolated this lipid body lipoxygenase from cucumber seedlings and found that it
      is capable of oxygenating in vitro di- and trilinolein to the corresponding mono
      , di-, and trihydroperoxy derivatives. To investigate the in vivo activity of
      this enzyme during germination, lipid bodies were isolated from cucumber
      seedlings at different stages of germination, and the triacylglycerols were
      analyzed for oxygenated derivatives by a combination of high pressure liquid
      chromatography, gas chromatography/mass spectrometry, and nuclear magnetic
      resonance spectroscopy. We identified as major oxygenation products
      triacylglycerols that contained one, two, or three 13S-hydroperoxy-9(Z),11(E)
      octadecadienoic acid residues. During germination, the amount of oxygenated
      lipids increased strongly, reaching a maximum after 72 h and declining afterward.
      The highly specific pattern of hydroperoxy lipids formed suggested the
      involvement of the lipid body lipoxygenase in their biosynthesis. These data
      suggest that this lipoxygenase may play an important role during the germination
      process of cucumber and other plants and support our previous hypothesis that the
      specific oxygenation of the storage lipids may initiate their mobilization as a
      carbon and energy source for the growing seedling.

PMID- 9261185
TI  - T cell receptor-induced phosphorylation of Sos requires activity of CD45, Lck,
      and protein kinase C, but not ERK.
AB  - Stimulation of the T cell antigen receptor (TCR) activates signaling pathways
      involving protein kinases, phospholipase Cgamma1, and Ras. How these second
      messengers interact to initiate distal activation events is an area of intense
      scrutiny. In this report, we confirm that TCR ligation results in phosphorylation
      of Sos, a guanine nucleotide exchange factor for Ras. This requires expression of
      both the CD45 tyrosine phosphatase and the Lck protein tyrosine kinase and
      depends upon signaling via protein kinase C. In contrast to previous studies
      examining requirements for Sos phosphorylation following insulin and epidermal
      growth factor receptor engagement, we show that TCR-induced phosphorylation of
      Sos does not require activation of the mitogen-activated protein
      kinase/extracellular-signal regulated kinase (MEK/ERK) pathway. However, the
      basal phosphorylation of Sos in T cells is affected by either MEK or MEK
      dependent kinases. Although Sos phosphorylation results in its dissociation from
      Grb2 following insulin stimulation in Chinese hamster ovary cells, TCR engagement
      on the Jurkat T cell line fails to elicit a similar effect. These data
      demonstrate that the kinases responsible for Sos phosphorylation differ following
      ligation of various cell surface receptors and that the consequences of Sos
      phosphorylation relies, at least in part, on sites of its phosphorylation.

PMID- 9261187
TI  - Translation of an uncapped mRNA involves scanning.
AB  - tat, an essential gene of human immunodeficiency virus, when placed under the
      control of the RNA polymerase III promoter from the adenovirus VA RNA1 gene, is
      transcribed into an uncapped and nonpolyadenylated mRNA. This VA-Tat RNA is
      translated to produce functional Tat protein in transfected mammalian cells
      (Gunnery, S., and Mathews, M. B. (1995) Mol. Cell. Biol. 15, 3597-3607). The
      presence of an upstream open reading frame (ORF) in VA-Tat RNA is inhibitory to
      the translation of the Tat ORF, suggesting that the RNA is scanned during
      translation even though it is uncapped. Because the effect of the upstream ORF is
      relatively small (about 2-fold), we sought more definitive evidence of scanning
      by introducing secondary structures of varying stabilities into the 5'
      untranslated region of VA-Tat RNA. The results of transfection experiments showed
      that highly stable secondary structure was inhibitory to Tat synthesis, whereas
      structures of lower stability were not inhibitory, confirming that uncapped mRNA
      is subject to scanning. Furthermore, translation of the downstream ORF was
      reduced but not eliminated by mutations that caused the upstream ORF to overlap
      the Tat ORF. Extending the overlap of the two ORFs further decreased the
      translation of the downstream ORF. This observation implies that ribosomes
      reinitiate after termination, possibly after migrating in a 3' to 5' direction
      through the overlap region of the mRNA. Similar results were obtained with a
      capped polymerase II transcript, indicating that the translation of polymerase II
      and polymerase III transcripts occurs through similar mechanisms.

PMID- 9261188
TI  - The effect of nitric oxide release rates on the oxidation of human low density
      lipoprotein.
AB  - 1-Substituted diazen-1-ium-1,2-diolates, a class of nitric oxide (. NO) donor
      compounds that spontaneously release .NO at different rates, were used to
      investigate the effect of .NO release rate upon the oxidation of low density
      lipoprotein (LDL). All donor compounds conferred an inhibitory effect upon the
      oxidation of LDL; however, the effect exhibited a biphasic dependence upon the
      rate of .NO release. The .NO release rate that maximally inhibited oxidation was
      dependent upon the rate of oxidation. When LDL was rapidly oxidized by copper(II)
      sulfate, a faster release rate was more effective. In contrast, when LDL was
      oxidized slowly by 2,2'-azobis-2-amidinopropane hydrochloride, a slower release
      rate was most effective. This biphasic relationship between .NO release rate and
      the duration of inhibition was also demonstrated when LDL oxidation was initiated
      with 5-amino-3-(4-morpholinyl)-1,2, 3-oxadiazolium, a peroxynitrite generator. We
      conclude that the antioxidant ability of .NO is dependent not only upon the rate
      of its release from .NO donors, but also upon the rate of oxidation. This
      conclusion is supported by a kinetic model of LDL oxidation in the presence of
      .NO.

PMID- 9261189
TI  - Native and modified low density lipoproteins increase the functional expression
      of the macrophage class B scavenger receptor, CD36.
AB  - The uptake of oxidized low density lipoprotein (OxLDL) by macrophages is a key
      event implicated in the initiation and development of atherosclerotic lesions.
      Two macrophage surface receptors, CD36 (a class B scavenger receptor) and the
      macrophage scavenger receptor (a class A scavenger receptor), have been
      identified as the major receptors that bind and internalize OxLDL. Expression of
      CD36 in monocyte/macrophages in tissue culture is dependent both on the
      differentiation state as well as exposure to soluble mediators (cytokines and
      growth factors). The regulatory mechanisms of this receptor in vivo are
      undetermined as is the role of lipoproteins themselves in modulating CD36
      expression. We studied the effect of lipoproteins, native LDL and modified LDL
      (acetylated LDL (AcLDL) and OxLDL) on the expression of CD36 in J774 cells, a
      murine macrophage cell line. Exposure to lipoproteins resulted in a marked
      induction of CD36 mRNA expression (4-8-fold). Time course studies showed that
      maximum induction was observed 2 h after treatment with AcLDL and at 4 h with LDL
      and OxLDL. Increased expression of CD36 mRNA persisted for 24 h with each
      treatment group. Induction of CD36 mRNA expression was paralleled by an increase
      in CD36 protein as determined by Western blot with the greatest induction by
      OxLDL (4-fold). In the presence of actinomycin D, treatment of macrophages with
      LDL, AcLDL, or OxLDL did not affect CD36 mRNA stability, implying that CD36 mRNA
      was transcriptionally regulated by lipoproteins. To determine the mechanism(s) by
      which lipoproteins increased expression of CD36 we evaluated the effects of
      lipoprotein components on CD36 mRNA expression. ApoB 100 increased CD36 mRNA
      expression significantly, whereas phospholipid/cholesterol liposomes had less
      effect. Incubation of macrophages with bovine serum albumin or HDL reduced
      expression of CD36 mRNA in a dose-dependent manner. Finally, to evaluate the in
      vivo relevance of the induction of CD36 mRNA expression by lipoproteins,
      peritoneal macrophages were isolated from mice following intraperitoneal
      injection of lipoproteins. Macrophage expression of CD36 mRNA was significantly
      increased by LDL, AcLDL, or OxLDL in relation to mice infused with phosphate
      buffered saline, with OxLDL causing the greatest induction (8-fold). This is the
      first demonstration that exposure to free and esterified lipids augments
      functional expression of the class B scavenger receptor, CD36. These data imply
      that lipoproteins can further contribute to foam cell development in
      atherosclerosis by up-regulating a major OxLDL receptor.

PMID- 9261190
TI  - [Renal ablation by transcatheter renal arterial embolization in the treatment of
      benign renal disease].
AB  - Renal ablation by transcatheter renal arterial embolization (TAE) was performed
      in 10 patients with benign renal disease (hydronephrosis n = 6; renovascular
      hypertension n = 3; nephrotic syndrome n = 1). Each affected kidney had little or
      no renal function. Six patients with hydronephrosis were treated with TAE using
      absolute ethanol alone in three patients and the combination of absolute ethanol
      and gelatin sponge in the other three. Each patient was followed by sclerotherapy
      of the pelvocalyceal system via nephrostomy using absolute ethanol. In four of
      the six patients, the embolized kidney had no urine, and there was very little
      urine in the remaining two. The size of the embolized kidney was markedly
      decreased on CT. The three patients with renovascular hypertension were pre
      studied by selective and renal vein sampling for PRA, and the kidney excreting
      higher renin was embolized by TAE with absolute ethanol. Blood pressure has
      become manageable without antihypertensive drug in two patients and with a
      reduced amount of drug in one. The patient with nephrotic syndrome had end stage
      renal failure and showed significant protein excretion. To prevent further
      protein loss, both kidneys were embolized with stainless steel coils. Urine
      output was significantly decreased, and consequently, hypoalbuminemia improved.
      All patients tolerated the procedure well, and there were no significant
      complications. Renal ablation by TAE may be an alternative to surgical treatment
      in selected patients with benign renal disease, particularly in patients with
      contraindications to surgery and in the elderly. Absolute ethanol and gelatin
      sponge seem safe and effective for TAE in patients with hydronephrosis and
      renovascular hypertension. For hydronephrosis, we recommend combining TAE with
      sclerotherapy of the pelvocalyceal system via nephrostomy using absolute ethanol.
      Though we successfully applied steel coil for the patient with nephrotic
      syndrome, absolute ethanol may be equally effective.

PMID- 9261191
TI  - [Measurement of cerebral blood flow in normal subjects by phase contrast MR
      imaging].
AB  - Global cerebral blood flow (CBF) was quantitatively measured with a two
      dimensional phase contrast cine magnetic resonance (MR) imaging technique in 24
      normal subjects (mean age, 38.6 years; range, 12-70 years). Cine transverse
      images of the upper cervical region (32 phases/cardiac cycle) were acquired with
      a 1.5 Tesla MR imaging unit. In five subjects, measurement of CBF was performed
      before and after intravenous administration of acetazolamide (DIAMOX, 15 mg/kg).
      Inter- and intraobserver variations in flow volume measurement were small (r =
      0.970, standard error of the estimate (SEE) = 2.9 ml/min, n = 80; r = 0.963, SEE
      = 4.6 ml/min, n = 40, respectively). In measuring flow velocity, they were
      inferior to those of flow volume measurement. On a visually determined setting of
      region of interest (ROI), reproducibly of the measurement of flow velocity was
      not satisfactory in this study. Thus only the results of flow volume measurement
      are presented. Mean summed vertebral flow volume (171 ml/min, SD = 40.6) was
      significantly less than mean summed internal carotid flow volume (523 ml/min, SD
      = 111). Total blood flow volume showed a significant decline with age (r = 0.45,
      p < 0.05). The mean proportions of carotid and vertebral flow volume to total
      flow volume were 75.3% and 24.7%, respectively, and showed no significant change
      with age. The left-to-right ratio of vertebral flow volume (1.39) was
      significantly higher than that of internal carotid flow volume (0.99, r = 0.05).
      After DIAMOX i.v., the mean rate of increase in total flow volume was 157%. Mean
      rates of increase in carotid and vertebral flow volume were 154% and 166%,
      respectively, which were not significantly different. In conclusion, this method
      is useful for estimating carotid and vertebral flow volume.

PMID- 9261192
TI  - [Clinical application of three dimensional ultrafast MR imaging to intracerebral
      traumatic lesions].
AB  - We applied a T1-weighted three-dimensional (3D) magnetization-prepared rapid
      gradient-echo sequence (MPRAGE) for the detection of intracerebral lesions
      associated with closed head injuries. Thirty-four patients underwent brain MR
      imaging on a 1.5 Tesla superconducting MR unit. We applied an MPRAGE sequence,
      together with spin echo (SE) and gradient echo (GRE) sequences, and evaluated the
      detectability of lesions with each sequence. A total of 100 intracerebral
      traumatic lesions (33 cortical contusion, 56 diffuse axonal injury, 11
      subcortical gray matter injury) were found. Ninety-seven percent of all lesions
      were detected on MPRAGE images, and 67% on SE and GRE images. The detectability
      of lesions in each category was 91%, 98%, and 100% on MPRAGE images, and 88%,
      54%, and 73% on either SE or GRE images. 3D MPRAGE is a promising method to
      detect intracerebral traumatic lesions, particularly those associated with
      diffuse axonal injury, because of its high quality of contrast and spatial
      resolution and the capability of image reconstruction in any plane.

PMID- 9261193
TI  - [Selective segmental necrotizing therapy for hepatocellular carcinoma: an
      experimental study of an ethanol injection method].
AB  - Selective segmental necrotizing therapy (SSN), which necrotizes the hepatic
      segment by ethanol injection through the intrahepatic portal vein under balloon
      occlusion, is a new treatment for hepatocellular carcinoma. To better perform
      this therapy safely and completely, the author examined an ethanol injection
      method using rabbits. A discolored area immediately formed in the injected area
      following rapid injection (injection speed > or = 1.0 ml/s) of absolute ethanol.
      This area became larger with increasing ethanol volume until it reached a
      plateau. The author defined the minimal volume as the minimal ethanol volume
      needed to form the maximal discolored area. The minimal volume correlated with
      the portal branch diameter of the injected area. A discolored area also formed
      when 50% or 25% ethanol was given by slow injection (injection speed < or = 0.1
      ml/s), similar to the case of using absolute ethanol by rapid injection. The area
      was recognized as a necrotic area on histological examinations 14 days after SSN.
      The blood ethanol level in the right atrium showed the slightest elevation when
      25% ethanol was given by slow injection. GPT showed the highest elevation 1 day
      after SSN, but it returned to normal 7 days after SSN in all ethanol injection
      methods. From these results, the author concluded that SSN should be performed
      using 25% ethanol by slow injection.

PMID- 9261194
TI  - [Radiation therapy for squamous cell carcinoma of uterine cervix using high dose
      rate intracavitary irradiation].
AB  - From January 1981 to December 1990, 214 uterine cervical squamous cell carcinomas
      were treated with external irradiation and high dose rate intracavitary
      irradiation (RALS). We used Henschke-type applicators for the vaginal ovoids
      during the intracavitary irradiation. According to the FIGO classification, 34
      cases were stage I, 76 stage II, 83 stage III and 21 stage IV. The 5-year
      survival rates of stage I, II, III and IV patients were 96.6%, 73.9%, 46.3% and
      26.1%, respectively. The incidence of local recurrence was 20.6%, that of distant
      metastasis 14.8% and that of late complication 14.0% in this series. These
      results are comparable to those previously reported. We think that Henschke-type
      applicators are suitable for women of advanced age because of the ease of
      insertion. The prognosis of patients who developed local recurrence or distant
      metastasis after irradiation was extremely poor. However, aggressive treatment
      for distant metastases prolonged survival, especially in patients with lymph node
      metastases.

PMID- 9261195
TI  - [Micro-wave local area network for radiological image transmission].
AB  - Shinshu University consists of five campuses in different locations, a situation
      that presents some problems in communication. To solve this problem, the Shinshu
      University Video and Data Network System (SUNS), which includes a high-speed
      audio-visual transfer function, has been developed and utilized for pre- and
      postgraduate education, administrative teleconferences, and local telephone (PBX)
      and Fax services. In 1988, a cooperative group for the study of radiographic
      image processing was organized, consisting of staff members of Shinshu University
      Hospital in Matsumoto, the Faculty of Engineering in Nagano (75 km from
      Matsumoto) and the Faculty of Textile Science and Technology in Ueda (45 km from
      Matsumoto). The system has been developed with a pair of personal computer (PC)
      based interactive image workstations and high-speed digital telecommunication
      interfaces to the SUNS. A transmission time of 878 kbps has been attained,
      including the time needed for read/write onto the PC hard disk. Image data thus
      transferred from the hospital have been utilized for the study of image
      processing by researchers in the Faculty of Engineering, and the processed images
      have been sent back to the hospital for evaluation of clinical efficacy of the
      processing by diagnostic radiologists. This kind of microwave network is a
      promising alternative for high-speed data transmission for radiological images
      and their processing.

PMID- 9261196
TI  - [Development of real-time CT fluoroscopy].
AB  - A new CT system that permits real-time monitoring of CT images was developed.
      Phantom and volunteer studies revealed that the images were displayed at a rate
      of six per second with a delay time of 0.83 second with clinically sufficient
      resolution (256 x 256) using the newly developed fast image processor and partial
      reconstruction algorithm. The clinical trial of stereotactic aspiration of
      intracerebral hematoma was successful. The initial trial with CT fluoroscopy
      revealed potential usefulness of the system in biopsy and other CT-guided
      interventions.

PMID- 9261197
TI  - [Usefulness of MR cholangiography with flex coil].
AB  - Fast SE MR cholangiography was performed in 10 healthy volunteers and 10 patients
      with biliary disease, using body, shoulder and flex coils. Surface coils provided
      better images than the body coil. Although high SNR images were obtained near
      surface coils, signal intensity decreased in areas distant from the shoulder
      coil. The flex coil greatly improved image quality, especially in intrahepatic
      bile ducts, compared with the shoulder coil. The application of a flex coil to MR
      cholangiography is a highly useful method to evaluate the biliary system.

PMID- 9261199
TI  - [High-resolution MR imaging of the mediastinum and hilus of the lung using
      surface-coils].
AB  - High-resolution MR imaging using surface-coils (Helmholtz-coil) was performed on
      patients with hilar lung cancer and healthy volunteers. We evaluated the clinical
      usefulness of this technique compared with MR imaging performed with a
      conventional body-coil. Although the signal-to-noise ratio was slightly
      decreased, normal anatomic structures, hilar masses, and enlarged lymph nodes
      were distinctly visualized in comparison with those on MR images obtained with a
      body-coil. High-resolution MR imaging with the Helmholtz-coil seemed to be useful
      for the evaluation of mediastinal and hilar disease, and may able to supplant MR
      imaging with a conventional body-coil in routine examinations.

PMID- 9261198
TI  - [New development of cellulose-ferric ammonium citrate solution as a contrast
      enhancement agent for magnetic resonance imaging of esophageal diseases].
AB  - For magnetic resonance imaging (MRI) of esophageal diseases, we have developed a
      new contrast-enhancement agent, cellulose-ferric ammonium citrate solution. Using
      this agent, the esophageal lumen is easily identified. This agent is expected to
      play a role in the MRI diagnosis of esophageal cancer and to help determine the
      indications for radical surgery and/or intracavitary irradiation.

PMID- 9261200
TI  - [MR imaging of traumatic head injuries using FLAIR technique].
AB  - The visualization of traumatic head injuries was compared between FLAIR images
      and standard long TR/TE images. FlAIR images were more sensitive than long TR/TE
      images in the detection of head injuries. We concluded that FLAIR images are
      better than conventional MR images in the evaluation of traumatic head injuries.

PMID- 9261201
TI  - [Thermotolerance and heat shock protein (HSP 70) in vascular endothelial cells].
AB  - Recently, it was determined that the endothelial cells of blood vessel play a
      very important physiological role in the regulation of blood coagulation and
      selective permeability. To study the thermotolerance of vascular endothelial
      cells, human umbilical vein endothelial cells (HUVEC) were heated at 40, 43, 45
      or 50 degrees C for various lengths of time with or without preheating at 40 or
      43 degrees C for 30 min. The cell viability (CV) of HUVEC decreased gradually
      according to heating time. However, the CV of preheated HUVEC decreased slightly
      or not at all. Heat shock protein (HSP) in HUVEC heated at 37, 40, 43, or 45
      degrees C was examined by immunoblotting. A new HSP 70 band was detected in HUVEC
      by heating at 40, 43 or 45 degrees C. HUVEC revealed thermotolerance with
      induction of HSP by heat stress.

PMID- 9261202
TI  - [Determinants associated with location of terminal care in the cancer patient].
AB  - Data relating to the place where terminal care was provided and where death was
      experienced were extracted from the charts of 100 terminally ill cancer patients
      who had been admitted to the first free-standing hospice in Japan. Of these 100
      patients who died between October 1993 and May 1995, 91 patients died in the
      hospice, five in the hospital, and only four at home. To clarify factors
      associated with the place where terminal care was provided to the cancer patient,
      the length of stay at home during the last 30 days of life was examined. We
      divided the 100 cases into two groups, group 1 comprising 60 cases who had spent
      less than seven days at home, group 2 comprising 40 patients who had spent seven
      days or more at home, and compared these two groups in terms of age, sex,
      diagnosis, strength of pain, morphine dosage, use of intravenous fluids,
      performance status, place of care before admission to hospice, awareness of
      having cancer, distance from the hospice, the number of family members in the
      household, and housing environment. Using multiple logistic regression, three
      factors are identified as significantly impedimental to staying at home: high
      morphine dosage (> 60 mg daily oral morphine equivalence), direct transfer from
      hospital to hospice, and living on the second or upper floors in an apartment
      building. The data suggest that the development of palliative home care and
      improvement of housing environment may enable cancer patients to spend more time
      at home during their terminal phase.

PMID- 9261203
TI  - [Evaluation of environmental stimulation for 18 months and the related factors].
AB  - With the disinteglation of social ties in the community, the role of
      environmental stimulation as an important function in children's health has been
      recognized and social services to evaluate the environmental stimulation are
      important. The Evaluation of Environmental Stimulation (EES) is a questionnaire
      which directly evaluates the interaction between the child and caregiver, and its
      effectiveness as a support system. The purpose of this study is to clarify
      characteristics of the EES by using statistical analysis. The subjects were 388
      children of about 18 months who came for the compulsory health examinations.
      Caregivers were asked to answer the questionnaire. The results are as follows; 1)
      Children at risk for physical, mental and social development scored low for the
      'social stimulation' subscale and in total score. 2) Children at the risk of
      medical and social diagnosis got fewer points in 'independence' subscale,
      'physical stimulation' subscale, and total score than children without risk. 3)
      By ANOVA statistics, risk for development and risk for medical and social
      diagnosis had interactions according to child's sex. These results show that EES
      is effective in finding the risk of environment for children and for development
      of prevention measures, and appears to be useful as a screening system for health
      social services.

PMID- 9261204
TI  - [Costs of health services for the elderly and related factors in cities of
      Japan].
AB  - OBJECTIVES: To estimate the costs of health services for the elderly in 1994 and
      to examine factors affecting them. METHODS: Questionnaires were sent to 631
      cities and responses from 339 cities were received. Data obtained from
      questionnaires were total cost, proportion of labor sent to total cost, cost per
      user, cost per person eligible to receive Health services for the elderly. These
      variables were measured for health counseling service, health education, health
      examinations, functional training, and home-visit guidance. RESULTS: The
      proportion of labor cost was smaller for health examinations than for other
      services. Health examinations and home-visit guidance showed higher correlation
      coefficients between the number of users and the total cost than other services.
      In most services, cost per eligible person were negatively correlated with the
      number of residents in the city and positively correlated with the number of
      public health nurses per resident. However, costs per user did not show a
      correlation. The cities which established municipal health centers had lower
      costs per user of health education and functional training than the cities which
      did not. Standardized mortality ratios of cerebrovascular disease and stomach
      cancer were not correlated with total cost, proportion of labor cost, cost per
      user, cost per eligible person in most services. CONCLUSIONS: For the economic
      evaluation of health services for the elderly, it is necessary to examine the
      relationship between cost, both quantity and quality, and effectiveness of health
      services.

PMID- 9261205
TI  - [Public health center based educational approach for families of the mentally
      disabled in Japan].
AB  - In order to evaluate a public health center based educational approach for
      families of the mentally disabled, questionnaires were sent to all public health
      centers in Japan. Out of 852 public health centers, 742 responded satisfactorily.
      At 68.6% of the 742 public health centers, some form of educational programs for
      families of the mentally disabled have been conducted. In a structured
      educational program, public health nurses and mental health counselors
      participated as the main staff. Training seminars for the staff were conducted by
      prefectural mental health centers or Zenkaren, The National Federation of
      Families with the Mentally Ill. In order to develop an educational program at the
      public health centers, the following three elements are required: 1) information
      transmitted through training seminars and publications, 2) trained staff members
      including mental health welfare counselors and public health nurses specialized
      in mental health, and 3) a sufficient budget. Further development of the program
      is considered crucial for a functional improvement of the public health centers.

PMID- 9261206
TI  - [Readmission among discharged psychiatric patients and it's correlates].
AB  - OBJECTIVE: This study investigated the incidence of readmission among discharged
      psychiatric patients and examined factors predicting early readmission. METHODS:
      A cohort of 343 patients, who had been hospitalized involuntarily to mental
      hospitals for medical care and custody, and who were discharged between April
      1991 and September 1993, in two areas served by Fukuoka Prefectural Yamato Health
      Center (n = 163) and Tagawa Health Center (n = 180) were followed up until
      November 1994. RESULTS: The readmission rates within 6 months of discharge in
      Yamato Health Center and Tagawa Health Center were 17% and 22%, and within 1 year
      were 30% and 31% respectively. From Cox's proportional hazards model,
      alcohol/drug abuse, many of previous admission, long length of recent
      hospitalization, payment of medical care cost from public assistance,
      complication of physical disorders, living without a person responsible for
      custody after discharge, no request of health center's service by the hospital
      and discharge from a large-scale mental hospital were significantly related to
      increased risk of readmission. Not a few patients could not be followed up
      completely because of early drop-out of treatment. The drop-out rates within 1
      month of discharge in Yamato Health Center and Tagawa Health Center were 10% and
      26%, and within 1 year were 15% and 27% respectively. CONCLUSIONS: The rates of
      readmission and drop-out of treatment among discharged psychiatric patients were
      considerably high. This study clarified that rapid establishment of a mental
      health system supporting the mentally disabled in a community is an urgent need
      in Japan.

PMID- 9261207
TI  - [Atopic dermatitis and related factors observed at infant physical examination at
      health centers].
AB  - We investigated the incidence of atopic dermatitis and related factors at infant
      physical examination at health centers. Subjects were 900 infants (290 four-month
      old infants, 298 one-year and six month-old infants, 312 three-year-old infants)
      who participated in infant physical examinations in Kanazawa-ku, Yokohama City.
      Overall, we analyzed 696 infants whose mothers had cooperated with the survey by
      completing questionnaires during physical examinations, and who submitted to
      examination by consulting dermatologists. The incidence of atopic dermatitis was
      11.6% in 4-month-old infants, 12.2% in 1.5-year-old infants, and 12.1% in 3-year
      old infants. The following were found to be related to the atopic dermatitis of
      infants. 1. Family history of atopic dermatitis in their mothers and older
      siblings. 2. Mothers' limited diet during pregnancy (avoiding some food which are
      suspected allergens). 3. Past history of molluscum contagiosum. 4. The frequency
      of taking bath. While epidemiological surveys of atopic dermatitis have
      previously been performed, the criteria at each survey was not identical and
      results could not be compared precisely. In this survey, 1. Dermatologists
      specializing in atopic dermatitis performed examinations. 2. All diagnoses were
      made according to standardized criteria which are applied nationwide. 3. All
      subjects were from a specific region. Because of this approach, this survey
      provides important information that can form the basis of comparison for future
      epidemiological surveys of atopic dermatitis.

PMID- 9261208
TI  - [HIV/AIDS counseling services for foreigners at the Shinjuku Public Health
      Center].
AB  - Since October 1994, the Shinjuku Public Health Center in collaboration with an
      NGO, has offered AIDS counseling services for foreigners. Although the NGO
      operated with volunteers before July 1995, the Center began budgeted HIV/AIDS
      counseling for foreigners from July 1995. The pre-HIV test counseling and post
      test counseling sessions were held twice a month, in English, Thai, Spanish and
      Portuguese. Counselors who speak those languages worked in coordination with
      staff members of the Center. Starting July 1995, counseling by telephone was also
      offered. During the 1 1/2 years, from October 1994 to March 1996, 600 people
      visited the Center for HIV tests and AIDS counseling, of whom 103 (17%) were
      foreigners. Among the 103 foreigners, one person was detected as seropositive.
      The 103 foreigners included 56 Thai speakers, 20 English speakers, 8 Portuguese
      speakers, 7 Spanish speakers and 12 people who speak other native languages
      (Chinese, Korean, Burmese, Iranian). From July 1995 to March 1996, (about 8
      months), 39 foreigners utilized the telephoned service for HIV test information:
      these 39 included 5 seropositive persons and AIDS patients. The number of
      foreigners visiting the Center for AIDS counseling and the number of foreigners
      utilizing the telephone service has increased each year. It is expected that the
      demand for these services will increase continuously in future.

PMID- 9261209
TI  - [Current status of HIV infection in Yunnan Province of China].
AB  - In cooperation with the Chinese Academy of Preventive Medicine and Yunnan
      Province Provincial Office for AIDS Control and Prevention, we studied the
      current status of HIV infection intravenous drug users (IVDUs) and other high
      risk groups in Yunnan province of China. As of the end of 1995, 1,807 HIV cases
      were officially reported (Positive rate was 0.6%), of which 1,278 (77.9%) were
      IVDUs, and 24 were their spouses. The majority of cases were found among the Dai
      minority male farmers near Ruili which borders on Myammar, but HIV also appears
      to be spreading among the Han people. HIV antibody positive rates among
      commercial sex workers, pregnant women and blood donors were 0.2%, 0.07% and
      0.04%, respectively. A system for surveillance of HIV has been developed, but
      preventive strategies to cope with HIV epidemic are not sufficient. As HIV/AIDS
      is now a global issue, (1) the integration and coordination of such preventive
      strategies in cooperation with community health workers, (2) general health
      education for condom use promotion and (3) care of psychological vulnerable
      person such as IVDUs, should be developed.

PMID- 9261210
TI  - [The HIV/AIDS Epidemic in Cambodia].
AB  - In December 1995 and March 1996, we visited institutes which were conducting
      epidemiological studied of HIV/AIDS in Cambodia, and obtained data for further
      collaborative study between Japan and Cambodia. Data included information on AIDS
      patients and HIV infected persons, and behavioral epidemiology of CSWs
      (Commercial Sex Workers). The cumulative reported number of AIDS patients and HIV
      infected persons in Cambodia was 86 and 2,536 cases respectively in 1995. The
      cause of infection was mostly heterosexual contact with very few cases from
      injecting drug use (IDU) and other causes. The seroprevalence rate of HIV
      antibody among donated blood rapidly increased from 0.08% in 1991 to 4.47% in
      1995, and those among CSWs and pregnant women were 37.9% and 2.6%, respectively,
      in 1995. The average rate of condom use among CSWs was 66%, but the rate of usual
      usage was only 14%. These results indicate that the HIV/AIDS epidemic had spread
      rapidly through CSWs, that it had been spread among peoples in communities, and
      that usage of condoms among CSWs was insufficient in Cambodia. Without strong
      countermeasures against HIV/AIDS in this country, HIV/AIDS epidemic may spread
      significantly to not only peoples in this country but also those in neighbouring
      countries in the future.

PMID- 9261211
TI  - [Structure-function study on gastric proton pump].
AB  - H+, K(+)-ATPase is a proton pump responsible for gastric acid secretion. It
      actively transport proton and K+ coupled with the hydrolysis of ATP, resulting in
      the formulation of a 10(6) fold proton gradient across the plasma membrane of
      parietal cells. The pump belongs to a family of P-type ATPases which include the
      Na+ pump (Na+, K(+)-ATPase) and the Ca2+ pump (Ca(2+)-ATPase). This review
      focuses on the structure-function relationship of this proton pump by using
      functional antibodies, specific inhibitor(s), a fluorescent reagent and site
      directed mutants. First we prepared monoclonal antibodies which modified the
      functions of the H+, K(+)-ATPase . One of the antibodies, HK2032 inhibited the
      H+, K(+)-ATPase activity and the chloride conductance in gastric vesicles opened
      by S-S cross-linking, suggesting that the chloride pathway is in the H+, K(+)
      ATPase molecule, and that the H+, K(+)-ATPase is a multi-functional molecule.
      Other antibody, HK4001 inhibited the H+, K(+)-ATPase activity by inhibiting its
      phosphorylation step. By using this antibody we found an H+, K(+)-ATPase isoform
      in the rabbit distal colon. Second we found that scopadulcic acid B, a main
      ingredient of Paraguayan traditional herb, is an inhibitor specific for the H+,
      K(+)-ATPase. This compound inhibited the H+, K(+)-ATPase activity by stabilizing
      the K(+)-form of the enzyme. Third we studied the conformational changes of the
      H+, K(+)-ATPase by observing the fluorescence of FITC-labeled enzyme. H+, K(+)
      ATPase did not utilize acetylphosphate instead the ATP as an energy source of
      active transport, suggesting that the energy transduction system is not common
      among P-type ATPases. Finally we constructed a functional expression system of
      the H+, K(+)-ATPase in human kidney cells. By using this functional expression
      system in combination with site-directed mutagenesis, we studied the significance
      of amino acid residues in the catalytic centers (a phosphorylation site and an
      ATP binding site) and the putative cation binding sites. We newly found the sites
      determining the affinity for cations.

PMID- 9261212
TI  - [Delivery system design for improvement of intestinal absorption of peptide
      drugs].
AB  - Most people drugs are hydrophilic molecules with a molecular weight between 300
      and 20,000 and such molecules are usually given by parenteral administration. In
      many cases, enteral administration of these peptides via the gastrointestinal
      tract is preferred. However, oral administration of peptides and proteins is
      often limited by their instability in the gastrointestinal environment and/or
      poor absorption from the gut. To promote the absorption of these drugs, we first
      discovered unsaturated fatty acids with absorption enhancing activities and less
      harmful properties to the gastrointestinal membranes in hydrolysates of natural
      oil. The mechanisms whereby the permeability of drugs was enhanced by the fatty
      acids are associated with the disorder in the membrane's interior and the
      interaction of these fatty acids with the polar head group of phospholipid.
      Furthermore, we suggested that a SH-related substance was involved in the
      permeability enhancing effect of these fatty acids. Secondly, we developed a
      lympho-targeting delivery system for bleomycin by the combined effects of an ion
      pair complex with dextran sulfate (DS) and an absorption enhancer. We found a
      very high lymphatic concentration when administered bleomycin-DS together with
      the absorption enhancer. Its mechanism may be due to a molecular sieving in the
      blood-lymph barrier in the intestinal tissues. Finally, to improve the intestinal
      absorption of peptides, we synthesized novel lipophilic derivatives of peptides
      including TRH (thyrotropin releasing hormone), tetragastrin, enkephalin,
      calcitonin and insulin by a chemical modification with fatty acids, while
      maintaining their pharmacological activities. The stability and permeability of
      these peptides were improved by acylation with some fatty acids having
      appropriate carbon numbers. Thus, we have established the strategies for
      improving the delivery of peptide drugs by various approaches. In future, the
      combination use of these approaches will be expected to develop the delivery
      systems of these drugs for therapeutic treatment.

PMID- 9261213
TI  - [Molecular characterization of intestinal absorption of drugs by carrier-mediated
      transport mechanisms].
AB  - It has long been thought that intestinal absorption of most of the drugs proceeds
      by passive diffusion mechanism, in which lipid solubility of the drug molecule is
      a determinant factor. However, water-soluble natural compounds such as amino
      acids and sugars can move across cell membranes by the specialized carrier
      mediated transport mechanisms. Although some drugs which are structurally
      analogous to natural compounds have been suggested to be absorbed by such
      transporters, no clear evidence for the involvement of carrier-mediated transport
      mechanisms has been obtained. In the present study, through the approach by means
      of the molecular cloning and functional expression of drug transporters as well
      as membrane physiological analysis for the drug transport across the intestinal
      epithelial cell membranes, participation of the carrier-mediated transport
      mechanisms for the drug absorption was clarified. They include peptide
      transporter, monocarboxylic acid transporter, anion antiporter, and P
      glycoprotein. Most of them have a function for the uptake of drugs into
      epithelial cells, leading to the increased absorption of drugs, whereas P
      glycoprotein excludes drugs into the lumen, thereby decreasing the apparent
      absorbability of drugs. A rat intestinal monocarboxylic acid-proton
      cotransporter, MCT1, and an anion antiporter, AE2, were suggested to contribute
      to the pH-dependent intestinal absorption of monocarboxylic acids such as benzoic
      acid, lactic acid, nicotinic acid, and valproic acid. An involvement of such pH
      dependent transporters in the intestinal absorption of weak organic acids is
      important, because they may have an alternative mechanism against passive
      diffusion according to the pH-partition hypothesis. PepT1 cloned from rat
      intestinal epithelial cells as a peptide transporter was clarified to localize at
      the intestinal epithelia brush-border membrane and to function for the absorption
      of beta-lactam antibiotics by the proton-gradient energized mechanism. In
      contrast, P-glycoprotein functions for the secretion of drugs into the intestinal
      lumen, thereby decreasing intestinal absorption of an immunosuppressive,
      cyclosporin A and a 5-HT3 receptor antagonist, azasetron. These lines of studies
      on the clarification of carrier-mediated drug absorption mechanisms will provide
      new knowledge for the strategies to the enhancement of intestinal absorption of
      drugs.

PMID- 9261214
TI  - [Physiological and pharmacological activities of simple alkyl- and
      arylpyrazines].
AB  - This review describes the physiological and pharmacological effect of simple
      alkyl- and arylpyrazines. The description is made in the following order 1) the
      presence of 2,5-dimethylpyrazine in the urine samples of human being and rodents
      2) the effects of tetramethyl- and tetraethylpyrazines on the vascular smooth
      muscles 3) the activity of alkyl- and arylpyrazines on the aggregation of
      arachidonic acid- and collagen-induced platelets 4) the effects of 2,5
      dimethylpyrazine on the reproductive and the accessory reproductive organs of
      female and male rats 5) the effects of 2,5-dimethylpyrazine on the plasma and on
      the contents of polyamines and fructose in the accessory reproductive organs of
      rats.

PMID- 9261216
TI  - Cut the fat.

PMID- 9261215
TI  - [Effect of tea extracts, catechin and caffeine against type-I allergic reaction].
AB  - The antiallergic effects of green tea, oolong tea, and black tea extracts by hot
      water were examined. These extracts inhibited the passive cutaneous anaphylaxis
      (PCA) reaction of rat after oral administration. Three tea catechins, (--)
      epigallocatechin (EGC), (--)-epicatechin gallate (ECg), and (--)-epigallocatechin
      gallate (EGCg) isolated from green tea showed stronger inhibitory effects than
      that of a green tea extract on the PCA reaction. The inhibitory effects of EGC
      and EGCg on the PCA reaction were greater than that of ECg. Caffeine also showed
      a inhibitory effect on the PCA reaction. These results indicate that tea could
      provide a significant protection against the type-I allergic reaction. These
      findings also suggest that tea catechins and caffeine play an important role in
      having an inhibitory effect on the type-I allergic reaction.

PMID- 9261217
TI  - Finance ... Catholic hospitals take a more conservative approach to collecting
      what's due them.

PMID- 9261218
TI  - Managed care. Spending on saving.

PMID- 9261219
TI  - Employers ... road signs intended help employers put the atlas to use.

PMID- 9261220
TI  - Human resources ... cutting corporate insurance costs.

PMID- 9261221
TI  - Technology ... laptops aren't much use when you don't have a lap to put them on.

PMID- 9261222
TI  - Physicians ... when doctors claim that they're "accredited".

PMID- 9261223
TI  - Education ... "social mission" costs incurred by academic medical centers.

PMID- 9261224
TI  - Faster. Stronger. Private? Stunted by politics and high costs, public hospitals
      convert to compete.
AB  - Public hospitals want out of politics. Executives say they need the freedom to
      cut costs--and deals--like everyone else. In a world where it's compete or die,
      many public hospitals are going private.

PMID- 9261225
TI  - Uncalculated risks. Why risk managers won't benchmark.
AB  - Risk managers are talking about the value of comparing error rates from hospital
      to hospital. But so far, competition and confidentiality stand in the way of wide
      spread benchmarking.

PMID- 9261226
TI  - The market made them do it. Participants in the Medicare Choices project say
      they're nudging out the insurance middleman--and insuring their own survival.
      Panel discussion.
AB  - Medicare is experimenting again. This time HCFA wants to figure out ways to
      expand managed care options for the elderly. Under the Medicare Choices
      Demonstration Project, hospitals and health systems are developing and testing
      alternatives to standard Medicare HMOs. Dick Davidson, president of the American
      Hospital Association, sees these pilot programs as the precursors to provider
      sponsored organizations building up a base of knowledge about what it means to
      manage risk. The AHA recently convened a meeting of organizations involved in the
      demonstration project and asked Hospitals & Health Networks executive editor
      Alden Solovy to lead a panel discussion on the lessons being learned.

PMID- 9261227
TI  - Policing ERISA. Plenty of bark, but no bite.

PMID- 9261228
TI  - Contingency planning. Learning the hard way.

PMID- 9261229
TI  - Mergers. So much for collegiality.

PMID- 9261230
TI  - Hospital watch. Apocalypse then.

PMID- 9261231
TI  - Don't tie the commission's hands.

PMID- 9261233
TI  - Management. Bed news is bad news.

PMID- 9261232
TI  - Quality watch. Making the grade.

PMID- 9261234
TI  - Research ... most people agree that there are too many uninsured children in the
      United States.

PMID- 9261235
TI  - Litigation ... Uncle Sam may have saved a lot of money by closing military bases.

PMID- 9261236
TI  - Long-term care ... San Francisco area may have to increase the number of nursing
      home beds.

PMID- 9261237
TI  - Medicare/Medicaid ... the most promising treatment for AIDS.

PMID- 9261239
TI  - "We're not Columbia". Tenet and other chains stand to profit from their
      competitor's troubles. But how different are they?
AB  - Tenet Healthcare bills itself as the kinder, gentler alternative to the nation's
      #1 for-profit hospital chain--ethically hip and financially strong. That helps
      woo hospital and community leaders who fear the specter of heavy-handed investor
      ownership. But is Tenet really all that different?

PMID- 9261238
TI  - Home health on the high wire. In the search for Medicare savings, politicians
      sidestep important structural questions.

PMID- 9261240
TI  - Organized chaos.
AB  - That's what you'll see if you put your organization under the microscope.
      Doctors, nurses and other staff work in ad hoc patterns that defy efficiency.
      Clinical integration is still more theory than practice, but a few determined
      pioneers aim to trample the chaos and replace it with order.

PMID- 9261241
TI  - Generation hex. Most management service companies are young, merging like mad-
      and losing money.
AB  - Cursed by financial losses and merger madness, today's breed of management
      service organizations faces similar challenges, according to a new survey by
      Medimetrix. This exclusive Executive Chartbook profiles MSOs and tracks key
      issues now and into the future.

PMID- 9261242
TI  - Public relations. Madonna slept here.

PMID- 9261243
TI  - Partnering. In this deal, three's a company.

PMID- 9261244
TI  - Elder care. Long-term scare.

PMID- 9261245
TI  - Employee benefits. Caught in the middle.

PMID- 9261246
TI  - Heterogeneity of endothelial cells. Specific markers.
AB  - During embryonic development, endothelial cells differentiate from a common
      precursor called angioblast and acquire organ-specific properties. One of the
      important determinants of endothelial cell differentiation is the local
      environment, and especially the interaction with surrounding cells. This
      interaction may occur through the release of soluble cytokines, cell-to-cell
      adhesion and communication, and the synthesis of matrix proteins on which the
      endothelium adheres and grows. The acquisition and maintenance of specialized
      properties by endothelial cells is important in the functional homeostasis of the
      different organs. For instance, in the brain, alteration of the blood-brain
      barrier properties may have important consequences on brain functional integrity.
      One of the major limitations to the study of endothelial cell heterogeneity is
      the fact that these cells are still difficult to isolate and culture from the
      microcirculation of different organs, and once in culture, they tend to lose
      their specialized properties. This finding suggests that we have to develop new
      culture systems, which possibly include coculture with other cell types. An
      important issue is to develop tools that can help in recognizing endothelial
      cells and their differentiated phenotype both in vivo and in tissue culture. In
      this review we give a short overview of the differentiated properties of the
      endothelium, considering a few examples of highly specialized endothelial cells,
      such as the brain or bone marrow microcirculation or high endothelial venules. We
      made a particular effort to list the most common markers of endothelial cell
      phenotypes. These molecules and related antibodies may be valuable tools for
      endothelial cell isolation and characterization.

PMID- 9261247
TI  - Smooth muscle cell heterogeneity in pulmonary and systemic vessels. Importance in
      vascular disease.
AB  - Experimental evidence is rapidly accumulating which demonstrates that the
      arterial media in both pulmonary and systemic vessels is not composed of a
      phenotypically homogeneous population of smooth muscle cells (SMCs) but rather of
      heterogeneous subpopulations of cells with unique developmental lineages. In vivo
      and in vitro observations strongly suggest that marked differences in the
      phenotype, growth, and matrix-producing capabilities of phenotypically distinct
      SMC subpopulations exist and that these differences are intrinsic to the cell
      type. These data also suggest that differential proliferative and matrix
      producing capabilities of distinct SMC subpopulations govern, at least in part,
      the pattern of abnormal cell proliferation and matrix protein synthesis observed
      in the pathogenesis of vascular disease. Within the pulmonary circulation, the
      observation that the isolated medial SMC subpopulations exhibit differential
      proliferative responses to hypoxic exposure is important, since this in vitro
      cell-model system can now be used to better understand the mechanisms that
      regulate increased responsiveness of specific medial cell subpopulations to low
      oxygen concentrations. Our data also support the idea that protein kinase C is
      likely to be one important determinant of differential cell growth responses to
      hypoxia. The data also suggest differential involvement of specific arterial SMC
      subpopulations in the elastogenic responses of the vessel wall to injury. We
      believe that a better understanding of the mechanisms contributing to the unique
      behavior of specific arterial cell subpopulations will provide important future
      directions for therapies aimed at preventing abnormal cell replication and matrix
      protein synthesis in vascular disease.

PMID- 9261248
TI  - Myosin gene expression and cell phenotypes in vascular smooth muscle during
      development, in experimental models, and in vascular disease.
AB  - In the aortic wall of mammalian species, the maturation phase of smooth muscle
      cell (SMC) lineage is characterized by two temporally correlated but opposite
      regulatory processes of gene expression: upregulation of SM type SM2 myosin
      isoform and downregulation of brain (myosin heavy chain B)- and platelet (myosin
      heavy chain A(pla))-type nonmuscle myosins. Using the myosin isoform approach to
      study vascular SMC biology, we have shown (1) a marked SMC heterogeneity in adult
      arterial vessels, ie, coexistence of an "immature" and a fully differentiated SMC
      population; and (2) the propensity of the immature type SMC population to be
      activated in experimental models and human vascular diseases that are
      characterized by proliferation and migration of medial SMCs into the
      subendothelial space.

PMID- 9261249
TI  - Effects of contraceptive estrogen and progestin on the atherogenic potential of
      plasma LDLs in cynomolgus monkeys.
AB  - This study was designed to determine the effect of oral contraceptive treatment
      (estrogen and progestin), alone or in combination, on LDL composition and
      atherogenic potential in cynomolgus monkeys fed an atherogenic diet. Groups (n =
      8 each) of monkeys were untreated (control) or treated with ethinyl estradiol
      (EE), levonorgestrel (LNG); or triphasic oral contraceptive (EE+LNG) for 1.5
      years before plasma LDLs were isolated for characterization. Total plasma
      cholesterol concentrations were unaffected by the treatments. LDL particle size
      (measured as LDL molecular weight, g/mumol) was significantly smaller, in the EE
      (4.61 +/- 0.09) and EE+LNG (4.43 +/- 0.09) treatment groups compared with the
      control (4.99 +/- 0.09) or LNG (5.29 +/- 0.17) groups and contained fewer
      molecules of free and esterified cholesterol. Both the EE and EE+LNG groups had
      significantly less cholesterol and apolipoprotein B distributed in the d = 1.015
      to 1.025 g/mL subfraction and correspondingly more in the d = 1.025 to 1.035 g/mL
      subfraction of LDL compared with the control and LNG groups. The apolipoprotein E
      content (molecules/particle) of LDL was significantly less in the EE (0.35 +/-
      0.1) and EE+LNG (0.28 +/- 0.1) groups compared with the control (0.86 +/- 0.2)
      and LNG (0.99 +/- 0.2) groups, and this trend was apparent in all three LDL
      subfractions. The atherogenic potential of LDL was tested using an in vitro
      binding assay to arterial proteoglycans. Twice as much LDL bound to arterial
      proteoglycans in the LNG group (11.3 +/- 1.8% of total LDL cholesterol in the
      incubation) compared with the control (6.4 +/- 1.9%), EE (5.5 +/- 1.5%), or
      EE+LNG (5.2 +/- 1.2%) groups. We conclude that EE and EE+LNG treatment alters the
      composition of LDL toward a less atherogenic particle that is smaller and more
      dense, contains less cholesterol and less apolipoprotein E, and is less reactive
      with arterial proteoglycans compared with LNG treatment. The inclusion of EE in
      the triphasic oral contraceptive treatment was sufficient to negate the
      potentially atherogenic effects of LNG on LDL composition.

PMID- 9261250
TI  - Effect of serum lipids, lipoproteins, and apolipoproteins on vascular and
      nonvascular mortality in the elderly.
AB  - The purpose of this study was to determine the effect of serum lipids,
      lipoprotein fractions, and apolipoprotein (apo) A-1, B and E on mortality from
      vascular and nonvascular causes in an unselected elderly population. The random
      sample of 347 community-living individuals aged 65 years or older was obtained in
      1982. Serum total cholesterol, LDL cholesterol (LDL-C), HDL cholesterol (HDL-C),
      triglyceride, and apo A-1, B and E were determined at baseline. After the 11-year
      follow-up, 199 of the participants had died, and 148 were still alive. Mortality
      data from vascular and nonvascular causes by the end of 1993 were obtained from
      official registers. In the univariate analysis, a low total cholesterol level was
      associated with death due to both vascular and nonvascular causes (P value for
      trend, .021 and .0027, respectively). After the adjustment for other risk
      factors, the inverse association between total cholesterol and vascular mortality
      disappeared, but low total cholesterol was still a significant predictor of death
      due to nonvascular causes. Adjusted relative risks (RRs) of death due to
      nonvascular causes for those with elevated total cholesterol (5.1 to 6.5, 6.6 to
      8.0, and > 8.0 mmol/L) compared with the reference group (< or = 5.0 mmol/L) were
      0.5 (95% confidence interval [CI], 0.2 to 1.2), 0.6 (0.2 to 1.0), and 0.2 (0 to
      0.8), respectively. Neither concentrations of HDL-C, LDL-C, triglyceride, nor apo
      B were associated with vascular or nonvascular mortality. On the other hand, low
      concentration of apo A-1 predicted vascular death. The RR for the lowest tertile
      was 1.6 (1.1 to 2.5) compared with the highest tertile. Furthermore, the
      occurrence of the apo E e4 allele was associated with increased risk of vascular
      mortality (RR, 1.5; 95% CI, 1.0 to 2.2), but the risk was not related to the
      levels of lipids, lipoproteins, or other apolipoproteins at baseline. Nonvascular
      mortality also tended to be predicted by the presence of the e4 allele (RR, 1.5;
      95% CI, 0.9 to 2.5). In an unselected elderly population, the allelic variation
      of apo E, i.e., the presence of the e4 allele, and a low concentration of apo A-1
      were more accurate indicators of vascular mortality than total cholesterol or
      lipoprotein fractions. The risk associated with the apo E polymorphism is
      unrelated to dyslipidemia.

PMID- 9261251
TI  - Increased immunolocalization of paraoxonase, clusterin, and apolipoprotein A-I in
      the human artery wall with the progression of atherosclerosis.
AB  - Using immunolocalization techniques, we have shown that paraoxonase (Pon),
      clusterin, and apolipoprotein (apo) A-I accumulate in the artery wall during the
      development of atherosclerosis. In normal aortas (n = 6) there were low levels of
      extracellular Pon, clusterin, and apoA-I, immunoreactivity. The cytoplasm of
      smooth muscle cells in the media showed granular positivity for both Pon and apoA
      I, indicating that these proteins were undergoing lysosomal degradation. This
      activity was also indicated by the presence of both intact and degradation
      products of Pon in smooth muscle cells as shown by Western blotting. With the
      progression of disease from fatty streaks (n = 3) to advanced atherosclerosis (n
      = 8) there was an increase in Pon, apoA-I, and clusterin immunoreactivity,
      indicating the increasing presence of these proteins with disease progression.
      These proteins are the components of a specific HDL subspecies that has been
      implicated in the prevention of peroxidative damage to phospholipids in LDL and
      membranes. The increase in Pon, clusterin, and apoA-I during the development of
      atherosclerosis may therefore represent a protective response to the oxidative
      stress associated with the development of atherosclerosis.

PMID- 9261252
TI  - Plasma acylation-stimulating protein in coronary artery disease.
AB  - To date, plasma levels of acylation-stimulating protein (ASP) have been
      determined only in normal and obese individuals. Accordingly. ASP was measured in
      fasting samples obtained from 59 age-matched controls and 208 patients with
      documented coronary artery disease (CAD). Overall, plasma ASP was significantly
      higher in the CAD subjects compared to the control subjects (55.3 +/- 1.8 nmol/L
      CAD versus 32.0 +/- 2.6 nmol/L control, P < .0005). In the control group, the
      distribution of plasma ASP values was unimodal whereas in the coronary group it
      was significantly skewed to the right. The coronary group was subdivided into
      those with pronounced elevation of apoB (a marked type II phenotype, n = 13),
      those with hypertriglyceridemia with a normal apoB (n = 17), and the remaining
      CAD subjects (n = 178). In the first two groups, ASP did not differ significantly
      from control subjects (43 +/- 2.8 nmol/L and 49 +/- 4.4 nmol/L respectively). By
      contrast, in the remaining CAD subjects, both the mean ASP level (56.8 +/- 2.0
      nmol/L, P < .001 by ANOVA) and the proportion of patients with a markedly
      elevated ASP (25.3% were > 95th percentile, P < .005 versus control by X2) were
      significantly increased. When this third group was divided into tertiles by
      plasma apoB and triglyceride there was a direct relationship between plasma ASP
      and these two parameters. Linear regression analysis demonstrated an association
      between plasma ASP and plasma triglyceride (P < .05), VLDL cholesterol (P <
      .025), and VLDL apoB (P < .05). Finally, when all of the CAD subjects were
      divided by apoE phenotype, there appeared to be a relationship between plasma ASP
      and apoE phenotype such that ASP was higher in E2 subjects, intermediate in E3
      subjects, and lower in E4 subjects. The present data document plasma ASP levels
      in a number of dyslipoproteinemic states and suggest a relation between the
      adipsin-ASP pathway and other metabolic determinants of lipoprotein metabolism.

PMID- 9261253
TI  - Angiotensin-converting enzyme gene and atherosclerosis.
AB  - Common variants of the angiotensin-converting enzyme (ACE) gene (ACE ie humans,
      Ace in mice) associated with changes in circulating ACE activities have been
      suggested to confer differential risks for atherosclerosis. Using a mouse model
      of atherosclerosis induced by heterozygosity for apolipoprotein E gene disruption
      and an atherogenic diet, we have studied the impact on atherogenesis of a
      mutation that changes the level of function of Ace. We find that this genetically
      determined change does not influence the size or complexity of atherosclerotic
      lesions. Ace genotype was not a significant determinant of lesion size in female
      (+/+ = 12.9 +/- 1.5 and +/- = 11.7 +/- 1.6 microns2 x 10(4)) or male (+/+ = 0.95
      +/- 0.25 and +/- = 1.83 +/- 0.59 microns2 x 10(4)) mice; however, lesions were
      significantly larger (P < .001) in female than male mice. Ace genotype also did
      not affect lesion complexity; however, lesions in females showed significantly
      increased frequency of cholesterol clefts, acellular cores, fibrous caps, and
      calcifications compared with those in males. The hypothesis that genetic
      variation in the level of ACE gene expression affects the development of
      atherosclerosis is not supported by these findings.

PMID- 9261254
TI  - Bimodal effects of angiotensin II on migration of human and rat smooth muscle
      cells. Direct stimulation and indirect inhibition via transforming growth factor
      beta 1.
AB  - Angiotensin II may be an important mediator of neointima formation in vascular
      disease. This study was designed to examine the mechanisms involved in
      angiotensin II-stimulated migration of human and rat aortic vascular smooth
      muscle cells (VSMCs). VSMCs were seeded in one corner of Nunc four-well culture
      chambers; angiotensin II within filter paper was glued onto the wall of the
      opposite side. After 48 hours of incubation in serum-free medium containing
      growth-arresting factor, migrated cells were counted using a light microscope.
      Angiotensin II (2 x 10(-11) to 2 x 10(-8) mol/L) increased migration of VSMCs in
      a concentration-dependent manner. Interestingly, at higher concentrations of
      angiotensin II (up to 2 x 10(-6) mol/L), migration was reduced to levels
      comparable with control levels. Losartan, an AT1 receptor antagonist, prevented
      migration, while PD123319, an AT2 receptor antagonist, had no significant
      inhibitory effect. Transforming growth factor-beta 1 (TGF-beta 1; 0.01 to 10.0
      pg/mL) inhibited migration induced by angiotensin II (2 x 10(-8) mol/L) in a
      concentration-dependent manner. A neutralizing TGF-beta antibody unmasked
      migratory effects of high concentrations of angiotensin II. Furthermore,
      angiotensin II (10(-6) mol/L) upregulated TGF-beta 1 mRNA levels fivefold in rat
      and fourfold in human VSMCs; this effect was prevented by losartan but not by
      PD123319. Thus, the effects of angiotensin II on migration of VSMCs are bimodal,
      ie, both migratory and antimigratory pathways are activated. Autocrine release of
      TGF-beta 1 induced by angiotensin II exerts an antimigratory effect in rat and
      human VSMCs. The AT1 receptor is involved in regulation of both pathways.

PMID- 9261255
TI  - Lysophosphatidylcholine promotes cholesterol efflux from mouse macrophage foam
      cells.
AB  - We examined the effects of lysophosphatidylcholine (lyso-PC) on promoting
      cholesterol efflux from macrophage foam cells. Mouse peritoneal macrophages were
      converted to foam cells by incubation with [3H]cholesteryl linoleate-labeled or
      unlabeled acetyl-LDL. When these cells were incubated with lyso-PC,
      [3H]cholesterol release was promoted in relation to both dose and time, and
      cellular cholesterol mass was decreased, while medium cholesterol mass was
      increased. These cholesterol efflux-promotive effects of lyso-PC were confirmed
      by the fact that the lyso-PC-treated cells showed less oil red O staining than
      the control cells. ApoE secretion, estimated by Western blotting of the medium,
      was also augmented by lyso-PC. Both the cholesterol and apoE released by lyso-PC
      treatment were floated by ultracentrifugation of the medium after its density had
      been adjusted to 1.210 g/mL. By electron microscopic analysis, vesicular
      lipoproteins were observed in ultracentrifugally concentrated conditioned medium
      of lyso-PC. Monensin, a protein secretion inhibitor, effectively inhibited
      [3H]cholesterol release induced by lyso-PC but not by apoA-I. These results
      suggest that lyso-PC may inhibit the development of atherosclerosis or enhance
      its regression by stimulating cholesterol efflux from macrophage foam cells.

PMID- 9261256
TI  - Human leukemia inhibitory factor upregulates LDL receptors on liver cells and
      decreases serum cholesterol in the cholesterol-fed rabbit.
AB  - In a previous study, we found that the cytokine (human) leukemia inhibitory
      factor (hLIF) significantly reduced plasma cholesterol levels and the
      accumulation of lipid in aortic tissues of cholesterol-fed rabbits after 4 weeks
      of treatment. The mechanisms by which this occurs were investigated in the
      present study. This involved examining the effect of hLIF on (1) the level of
      plasma cholesterol at different times throughout the 4-week treatment and diet
      period; (2) smooth muscle cell (SMC) and macrophage-derived foam cell formation
      in vitro; and (3) LDL receptor expression and uptake in the human hepatoma cell
      line HepG2. At time zero, an osmotic minipump (2-mL capacity; infusion rate, 2.5
      microL/h; 28 days) containing either hLIF (30 micrograms kg-1.d-1) or saline was
      inserted into the peritoneal cavity of New Zealand White rabbits (N = 24).
      Rabbits were divided into four groups of six animals each. Group 1 received a
      normal diet/saline; group 2, a normal diet/hLIF; group 3, a 1% cholesterol
      diet/saline; and group 4, a 1% cholesterol diet/hLIF. hLIF had no effect on the
      plasma lipids or artery wall of group 2 rabbits (normal diet). However, in group
      4 rabbits, plasma cholesterol levels and the percent surface area of thoracic
      aorta covered by fatty streaks was decreased by approximately 30% and 80%,
      respectively, throughout all stages of the 4-week treatment period. In vitro,
      hLIF failed to prevent lipoprotein uptake by either SMCs or macrophages (foam
      cell formation) when the cells were exposed to beta-VLDL for 24 hours. In
      contrast, hLIF (100 ng/mL) added to cultured human hepatoma HepG2 cells induced a
      twofold or threefold increase in intracellular lipid accumulation in the medium
      containing 10% lipoprotein-deficient serum or 10% fetal calf serum, respectively.
      This was accompanied by a significant non-dose-dependent increase in LDL receptor
      expression in hLIF-treated HepG2 cells incubated with LDL (20 micrograms/mL) when
      compared with controls (P < .05) incubated in control medium alone (P < .05). We
      suggest that the hLIF-induced lowering of plasma cholesterol and tissue
      cholesterol levels (inhibition of fatty streak formation) in the hyperlipidemic
      rabbit is due in part to upregulation of hepatic LDL receptors, with resultant
      increased clearance of lipoprotein-associated cholesterol from the circulation.
      There is an additional and as-yet-unknown mechanism acting at the level of the
      vessel wall that appears to be affecting the process of arterial cholesterol
      accumulation.

PMID- 9261258
TI  - PDGF receptor protein tyrosine kinase expression in the balloon-injured rat
      carotid artery.
AB  - Platelet-derived growth factor (PDGF) receptor gene expression has previously
      been demonstrated in balloon-injured rat carotid arteries to be regulated during
      repair of carotid injury. In the present study we showed that PDGF receptor
      protein expression and phosphorylation are changed over time after carotid artery
      injury. In control and 2-day-postinjury vessels, expression of PDGF alpha
      receptor protein was readily detectable, whereas PDGF beta receptor expression
      appeared very low. Between 2 and 7 days postinjury, a time interval previously
      shown to correspond with smooth muscle cell migration followed by the appearance
      of a neointima, PDGF alpha receptor expression had increased only slightly, to
      roughly 35% above control levels, and was maximal by day 7 postinjury, whereas
      PDGF beta receptor expression had doubled. From 7 to 14 days after carotid
      injury, intimal area was greatly increased and was associated with a further
      increase in PDGF beta receptor protein expression and receptor phosphorylation to
      a maximum between days 10 and 12. In contrast, PDGF alpha receptor expression had
      decreased slightly during this time interval. Moreover, phosphorylation of PDGF
      alpha receptors was barely detectable and did not change over the time course of
      injury. From 14 to 28 days after injury, intimal area was increased only
      slightly, whereas PDGF beta receptor protein and phosphorylation levels had
      diminished to roughly half of the 10-day injury values. In addition, the increase
      in PDGF beta receptor protein expression and tyrosine phosphorylation observed
      over the time of injury were also associated with a corresponding increase in the
      association of phosphatidylinositol 3' kinase (PI-3 kinase) with phosphorylated
      PDGF beta receptors. These findings show that balloon injury to rat carotid
      arteries results in temporally related changes in the expression of PDGF
      receptors and their state of tyrosine phosphorylation. Furthermore, tyrosine
      phosphorylation of PDGF beta receptors in the balloon-injured rat carotid artery
      in vivo resulted in the association of PI-3 kinase. These are important new
      findings, which add to our knowledge concerning the role and activity of PDGF
      receptors in the formation of a neointima.

PMID- 9261257
TI  - Low-affinity thromboxane receptor mediates proliferation in cultured vascular
      smooth muscle cells of rats.
AB  - We examined the binding properties and mitogenic effects of U46619, using
      cultured vascular smooth muscle cells (VSMCs), by ligand-binding assay, measuring
      [3H]thymidine and [3H]leucine incorporation, checking with flow cytometry, and
      counting the cell number. The U46619-activated mitogenic signal-transduction
      pathway was assessed by measuring formation of inositol monophosphate (IP);
      [Ca2+]i; mitogen-activated protein kinase (MAPK), MAPK kinase (MAPKK), and p74raf
      1 activities; and GTP-bound Ras. [3H]U46619 bound to cultured VSMCs from Wistar
      Kyoto (WKY) rats at a single class of site (Kd: 15.5 +/- 2.6 nmol/L). However, it
      bound to VSMCs from spontaneously hypertensive rats (SHRs) at two classes of
      sites (Kd: 2.3 +/- 0.6 nmol/L and 1.4 +/- 0.5 mumol/L). U46619 increased DNA and
      protein synthesis, cell number, IP formation, [Ca2+]i, and MAPK and MAPKK
      activities, with EC50 values close to its Kd value for the low-affinity binding
      site in VSMCs from SHR. Prostaglandin (PG) E2 and PGF2 alpha showed little of
      such mitogenic effects. All these effects of U46619 were inhibited by SQ29548,
      staurosporine, or pretreatment of VSMCs with phorbol 12-myristate 13-acetate for
      24 hours. However, U46619 stimulation did not lead to a significant increase in
      the Ras-GTP complex or p74raf-1 activity. In conclusion, the mitogenic effect of
      U46619 appears to be mediated via the activation of low-affinity thromboxane
      binding sites that trigger phosphoinositide hydrolysis and activate the MAPK
      pathway, leading to DNA synthesis and cell proliferation.

PMID- 9261259
TI  - Effect of probucol treatment on gene expression of VCAM-1, MCP-1, and M-CSF in
      the aortic wall of LDL receptor-deficient rabbits during early atherogenesis.
AB  - Probucol is a potent inhibitor of atherosclerosis in animal models. However, the
      mechanism of its antiatherogenic effect is not known. To investigate the effects
      of probucol on gene expression of VCAM-1, MCP-1, and M-CSF in vivo during the
      early stages of atherogenesis, we determined gene expression in 12 control WHHL
      rabbits and 12 WHHL rabbits fed 1% probucol from age 3 weeks. Three animals from
      each group were killed at 6, 9, 12, and 18 weeks of age. Two intimal/medial
      segments of the thoracic aorta, each comprising the orifices of a pair of
      intercostal arteries, were analyzed by semiquantitative RT-PCR using GAPDH as an
      internal standard. A third segment located between these two segments was studied
      by immunocytochemistry. A basal level of VCAM-1 gene expression was observed in
      lesion-free aortas of both treated and untreated WHHL rabbits (and in normal NZW
      aortas). Immunocytochemistry showed some VCAM-1 protein in normal arteries and
      confirmed that VCAM-1 protein expression generally correlated with gene
      expression. In the untreated WHHL rabbits, a marked upregulation of VCAM-1
      expression was observed at 18 weeks. To correlate gene expression with intimal
      monocyte/macrophages in each animal, the macrophage area was determined by
      morphometry of immunostained sections. In addition, a scoring system of lesions
      was used. VCAM-1 expression showed a highly significant correlation with the
      extent of intimal macrophage presence (P < .001). A lesser degree of correlation
      between gene expression and macrophage accumulation was also seen for MCP-1. In
      contrast, M-CSF expression remained constant over the entire study period and
      showed no correlation with the intimal macrophage accumulation. Probucol
      treatment completely prevented lesion formation in all animals up to 18 weeks of
      age. Probucol reduced the level of basal VCAM-1 expression and prevented its
      upregulation. MCP-1 expression was not affected by probucol treatment, whereas M
      CSF expression was significantly lowered by probucol. Our results support the
      idea that VCAM-1 plays an important role in early atherogenesis and suggest that
      the antiatherogenic effect of probucol may in part be due to a downregulation of
      VCAM-1. Reduction of the basal level of M-CSF gene expression by probucol
      treatment may also contribute to its ability to inhibit atherogenesis.

PMID- 9261260
TI  - Inhibitory effects of hypercholesterolemia and ox-LDL on angiogenesis-like
      endothelial growth in rabbit aortic explants. Essential role of basic fibroblast
      growth factor.
AB  - Hypercholesterolemic (HC) rabbits exhibit suppressed compensatory vascular growth
      after restriction of arterial supply. However, neovascularization is commonly
      found in atheromas containing inflammatory cells. We used an in vitro model to
      determine the effects of hypercholesterolemia on angiogenesis in the absence or
      presence of inflammatory cells. HC rabbit aortic explants (1 mm2) with or without
      (n = 90 each) lesion-forming inflammatory cells were cultured in a collagen
      matrix with serum-free medium. Explant-derived endothelial cell growth was
      organized into capillary-like microtubes (CLM) that could be videomicroscopically
      quantified. CLM growth from lesion-free HC explants was significantly reduced to
      13 +/- 4% of the value in explants (n = 90) from normocholesterolemic (NC, n =
      15) rabbits (P < .001). In contrast, in lesion-containing HC explants, the matrix
      was invaded by foam cells, and CLM growth was not inhibited. Immunoassayable
      basic fibroblast growth factor (bFGF, in pg/mL) in the culture medium was
      significantly lower in lesion-free HC (< 5) than NC explants (11 +/- 2, P < .01)
      or HC explants with lesions (14 +/- 3). In addition, CLM growth was reduced in NC
      explants incubated with oxidized LDL (ox-LDL, 50-100 micrograms/mL). Exogenous
      bFGF (10 ng/mL) reversed the inhibitory effects of hypercholesterolemia and ox
      LDL, whereas bFGF-neutralizing antibody (10 micrograms/mL) abolished CLM growth
      in all groups. In cultured rabbit aortic endothelial cells, ox-LDL reduced DNA
      synthesis, but this inhibition was reversed by bFGF. We conclude that
      hypercholesterolemia and ox-LDL inhibit angiogenesis like endothelial growth
      because of a suppressed availability of endogenous bFGF. Retained responsiveness
      to exogenous bFGF suggests that inducing bFGF expression at targeted sites may
      improve collateral growth in hyperlipidemic arterial disease.

PMID- 9261261
TI  - Modulation of tissue factor protein expression in experimental venous bypass
      grafts.
AB  - Vein graft failure is a major limitation of coronary artery and peripheral
      vascular surgery. Tissue factor (TF), a transmembrane glycoprotein, generates
      thrombin by initiating the extrinsic coagulation cascade and plays a major role
      in the response to arterial injury. This study was designed to examine changes in
      TF protein expression in response to venous bypass grafting. New Zealand White
      rabbits underwent interposition bypass grafting of the common carotid artery via
      the ipsilateral external jugular vein. The contralateral control jugular veins (n
      = 6), early vein grafts (1 or 3 days after grafting, n = 18), and late vein
      grafts (14 or 28 days after grafting, n = 8) were examined by
      immunohistochemistry. The presence or absence of TF immunostaining in the intima
      was assessed in each vessel quadrant. In control veins, intimal TF staining was
      present in 5 of 24 vessel quadrants. In early vein grafts, TF staining was
      markedly increased in the intima (72 of 72 quadrants, P < .001 vs control veins),
      and TF immunostaining colocalized with CD18-positive leukocytes but not with
      endothelial cells, vascular smooth muscle cells, or RAM11-positive macrophages.
      In late vein grafts with intimal hyperplasia, TF expression was low or absent in
      the intima (6 of 32 quadrants, P < .001 vs early vein grafts; P = NS vs control
      veins), although medial smooth muscle cells expressed TF. Marked changes in TF
      expression occur in vein grafts. In early vein grafts, TF protein was greatly
      increased in the intima for at least 3 days and was associated with CD18-positive
      leukocytes. In late vein grafts with intimal hyperplasia, however, TF protein was
      not seen in the intima. These findings may have important implications for the
      development of therapeutic strategies to limit vein graft failure.

PMID- 9261262
TI  - D-dimer and anticoagulation in patients with mechanical prosthetic heart valves.
      A 2-year follow-up.
AB  - The best anticoagulation level in patients with mechanical heart valve prostheses
      is still being debated. D-dimer, which detects the presence of cross-linked
      fibrin degradation products, has been demonstrated to be a useful marker of
      coagulation activation. This study was designed to verify whether heart valve
      prostheses in anticoagulated patients are associated with abnormalities in D
      dimer plasma levels, and if so, whether such levels are related to the
      anticoagulation level and/or whether they could be predictive of acute vascular
      or hemorrhagic events. In 132 patients with single and 10 with double mechanical
      valve replacement, international normalized ratio (INR) and D-dimer plasma levels
      were determined. The INR levels of the previous 8 months were reviewed to assess
      the time that each patient spent in the therapeutic range. The D-dimer plasma
      levels were compared with those obtained from 102 matched control subjects. The
      patients were then followed up for 2 years to record acute vascular and
      hemorrhagic events. For the entire group, D-dimer plasma levels in patients were
      the same as those in the control group. Patients with double valve replacement
      had higher D-dimer plasma levels than either monovalvular implant patients or
      control subjects. Patients who had spent < 75% of the time within the assigned
      anticoagulation range had higher values for D-dimer plasma levels (median, 270 vs
      198 ng/mL, P = .02). The major determinants of D-dimer plasma levels were age (R2
      = .07, P = .009) and the percentage of time spent below the predetermined INR
      level (R2 = .09, P = .001). During follow-up, 19 acute vascular and 16
      hemorrhagic events occurred. High D-dimer tertile was the only parameter
      predicting the occurrence of thromboembolic events. In patients with mechanical
      heart valve prostheses, the D-dimer plasma level depended on the thoroughness of
      anticoagulation. Patients in the upper tertile of D-dimer values have an
      approximately 5-fold risk of vascular thromboembolic events. D-dimer
      determination can therefore be useful in detecting patients who are at a higher
      risk of severe vascular events.

PMID- 9261263
TI  - Persistent thrombin generation during heparin therapy in patients with acute
      coronary syndromes.
AB  - Intravenous heparin, a fundamental therapy in the treatment of patients with
      acute coronary syndromes, acts by inhibiting thrombin and activated factors X,
      IX, XI, and XII. It has also been demonstrated that heparin reduces plasma
      fibrinopeptide A, a marker of thrombin activity, but it is unknown whether it
      decreases prothrombin fragment 1+2, an indirect marker of thrombin generation. We
      measured the plasma levels of prothrombin fragment 1+2, fibrinopeptide A, and
      antithrombin III in 64 consecutive patients with unstable angina or myocardial
      infarction receiving intravenous heparin. Blood samples were obtained at baseline
      (before any treatment) and then at 90 minutes and 24 and 48 hours after the
      administration of an intravenous bolus of heparin (5000 IU) followed by a
      continuous infusion of 1000 IU per hour to maintain activated partial
      thromboplastin time at more than double its baseline levels. In comparison with
      baseline, there was a significant decrease in fibrinopeptide A at 90 minutes and
      at 24 and 48 hours (baseline, 2.3 nmol/L; 90 minutes, 1.15 nmol/L; 24 hours, 1.4
      nmol/L; 48 hours, 1.2 nmol/L; P < .0001) but no change in prothrombin fragment
      1+2 levels (baseline, 1.27 nmol/L; 90 minutes, 1.3 nmol/L; 24 hours, 1.33 nmol/L;
      48 hours, 1.29 nmol/L; P = NS). Antithrombin III activity decreased at 24 and 48
      hours (baseline, 108%; 24 hours, 97%; 48 hours, 95%; P < .0001). Hence, in
      patients with acute coronary syndromes, intravenous heparin at a dose reaching an
      activated partial thromboplastin time that adequately suppresses thrombin
      activity does not suppress increased thrombin generation.

PMID- 9261264
TI  - Platelet activation in flowing blood passing growing arterial thrombi.
AB  - We investigated the combined effect of wall shear rate and immobilized collagen
      on platelet activation in flowing nonanticoagulated human blood. By combining an
      ex vivo model of thrombogenesis with flow cytometry, we showed that activated
      platelets can be detected in the bloodstream passing growing thrombi at a wall
      shear rate characteristic of moderately stenosed arteries (2600 s-1). The
      activation of the circulating platelets was clearly correlated with thrombus
      growth. Different antibodies against platelet activation-dependent surface
      markers had distinct sensitivity to the thrombotic process. alpha-Granule release
      detected by surface expression of CD62P seemed to be the most sensitive marker,
      as judged by both mean fluorescence intensity and fraction of platelets
      activated. The conformational change in glycoprotein IIb-IIIa, as detected by PAC
      1, also seemed to be a sensitive marker and preceded binding of fibrinogen to
      activated glycoprotein IIb-IIIa, as detected by anti-fibrinogen. Large thrombi
      also elicited lysosome exocytosis, detected by surface expression of CD63.
      Finally, we observed a small decrease of glycoprotein Ib-IX expression, as
      detected by anti-CD42a. Thus, our study provides further information on the
      dynamics of platelet activation in relation to thrombus growth at arterial shear
      conditions in flowing nonanticoagulated human blood.

PMID- 9261265
TI  - Relation of plaque lipid composition and morphology to the stability of human
      aortic plaques.
AB  - The propensity of atherosclerotic plaques to disrupt may be influenced by their
      lipid content and the distribution of these lipids within the plaque. To
      investigate this, we analyzed the morphological and lipid profiles of 668 human
      aortic plaques from 30 males who had died of ischemic heart disease. Plaques were
      classified as disrupted or as intact types A or B, the latter distinction being
      based on the absence or presence, respectively, of disrupted plaques within the
      same aorta. Disrupted plaques have a greater content of lipid (P < .001) and
      macrophages (P < .001) as well as a thinner cap (P < .001) than intact plaques.
      Lipid concentrations are positively associated with macrophage accumulation in
      all plaque types and are negatively associated with minimum cap thickness at the
      edge of disrupted plaques (P < .05). Free cholesterol concentration is inversely
      associated with minimum cap thickness at the center of type B plaques only (P <
      .05). At the center of intact type A and B and disrupted plaques, the free-to
      esterified cholesterol ratios were 0.9 (range, 0.0 to 2.7), 0.8 (0.0 to 3.9), and
      1.6 (0.2 to 4.0), respectively. Esterified cholesterol concentrations were higher
      at the center of type B plaques, and those of free cholesterol were higher at the
      center of disrupted plaques. At the edge of disrupted plaques, the free-to
      esterified cholesterol ratio was 0.5 (0.0 to 2.7) because of the accumulation of
      esterified cholesterol. Concentrations of all fatty acids were increased at the
      edge of disrupted plaques compared with the center, but as a proportion of total
      fatty acids, omega 6-polyunsaturated fatty acids (PUFAs) were lower (44% versus
      46%, P < .01), possibly reflecting oxidation of PUFAs. These data demonstrate
      differences in lipid composition and intraplaque lipid distribution between
      intact and disrupted plaques. At the edge of advanced plaques, increased
      esterified lipid concentrations, inversely associated with cap thickness, may
      reflect macrophage activity and a predisposition to rupture.

PMID- 9261266
TI  - In vivo/in vitro comparison of rat abdominal aorta wall viscosity. Influence of
      endothelial function.
AB  - Arterial wall viscosity (AWV) is a potential source of energy dissipation in
      circulation. That arteries, which are known to be markedly viscous in vitro, have
      lower viscosity in vivo has been suggested but not demonstrated under similar
      pressure conditions. Endothelium, which may modulate AWV through smooth muscle
      tone, could contribute to the low level of viscosity in vivo. Our objectives were
      first to compare AWV of the rat abdominal aorta, in vivo and in vitro, with
      similar pulse-pressure waves, and second, to determine whether endothelial
      function influences AWV in vivo and in vitro. The diameter of the abdominal aorta
      and distending pressure were measured in vivo and in vitro with a high-resolution
      echotracking system and a micromanometer, respectively. AWV was calculated as the
      area of the pressure-volume curve hysteresis. After in vivo examination, the
      arterial segments were isolated in vitro and submitted to resynthesized pressure
      waves identical to those recorded in vivo. Deendothelialization was performed in
      vivo by balloon rubbing; then arteries were examined either in vivo or in vitro.
      AWV was markedly lower in vivo than in vitro (6.6 +/- 0.7 versus 22.7 +/- 3.7 J.m
      1.10(-5), respectively; P < .001). After deendothelialization, a sustained 40%
      increased AWV was observed during a 15-minute follow-up (P < .01). In vitro,
      deendothelialized arteries have a 64% higher AWV than segments with endothelium
      (P < .01). Our results indicate that the physiological effective viscosity,
      measured in vivo in intact animals, is threefold lower than the intrinsic
      viscosity of the arterial wall, measured in vitro. Endothelium removal determines
      a sustained increase in AWV, either in vivo or in vitro. These results suggest
      that active mechanisms compensate for intrinsic viscosity under physiological
      conditions. One of these energy-saving mechanisms might be dependent on normal
      endothelial function.

PMID- 9261267
TI  - Influence of the geometry of the left main coronary artery bifurcation on the
      distribution of sudanophilia in the daughter vessels.
AB  - The proximal portions of the left anterior descending (LAD) and left circumflex
      (LCx) coronary arteries are among the sites most predisposed to atherosclerotic
      disease. This predisposition might be a consequence of their location immediately
      distal to the left main (LM) coronary artery bifurcation, which may increase the
      susceptibility of these segments by promoting an adverse fluid dynamic
      environment within them. The detailed geometry of the bifurcation influences this
      environment and would therefore affect the susceptibility of the proximal
      daughter vessels to disease. This hypothesis was tested by examination of the
      relationship between the geometry of the LM bifurcation and the distribution of
      sudanophilia in the proximal portions of the LAD and LCx. The geometric
      parameters at the LM bifurcation, including all three angles and LM length, were
      obtained from multiangle photographs of 17 vascular casts by use of objective
      computer-based algorithms. A robust index, the relative proximal involvement
      (RPI), was developed to measure the localization of disease to the proximal
      portions of the daughter vessels. The RPI of the LAD segment correlated best with
      an interaction term that included the planarity of the LM bifurcation and the LCx
      LAD branch angle (P = .013). In addition to supporting the concept of geometric
      risk factors, these observations also suggest that interactions between the
      hemodynamic influences of multiple geometric variables may play a role in the
      mediation of tissue susceptibility by geometric factors.

PMID- 9261268
TI  - Changes with age in the influence of endogenous nitric oxide on transport
      properties of the rabbit aortic wall near branches.
AB  - Uptake of circulating albumin by the aortic wall is greater downstream than
      upstream of branches in immature rabbits, but the opposite pattern occurs in
      mature animals. We investigated the role of NO in determining these variations.
      Descending thoracic aortas of rabbits were cannulated using techniques that avoid
      depressurization, overstretching, and excessive fluid dynamic stresses at the
      endothelial surface. They were perfused in situ at a constant pressure and flow
      rate with oxygenated, protein-containing physiological buffer, with or without N
      omega-monomethyl-L-arginine, an inhibitor of NO synthesis. Aortas were fixed 7 to
      8 minutes after the addition of rhodamine-labeled albumin to this perfusate, and
      uptake of the tracer near intercostal ostia was measured by digital imaging
      fluorescence microscopy of sections through the wall. Despite the absence of
      pulsatile flow, blood cells, and many plasma components, patterns of transport in
      control experiments were the same as those occurring in vivo; uptake was greatest
      downstream of ostia in immature vessels and upstream in mature ones, although
      mean uptake was higher than previously reported. In the presence of the
      inhibitor, mean uptake in immature arteries was elevated threefold and the
      maximum tracer concentration occurred deeper in the wall, but there was no change
      in the fractional difference between regions. Conversely, the reverse of the
      control pattern of transport was observed in mature arteries exposed to the
      inhibitor, but there was no change in mean uptake. The reversal was almost
      entirely prevented by adding excess L-arginine to the perfusate and was largely
      stereospecific. Endogenous NO thus appears to determine the mature pattern of
      transport near branches and helps to maintain the barrier function of the
      immature wall.

PMID- 9261270
TI  - Skipping of exon 14 and possible instability of both the mRNA and the resultant
      truncated protein underlie a common cholesteryl ester transfer protein deficiency
      in Japan.
AB  - Among the Japanese population, a G-to-A mutation at the beginning of intron 14 of
      the human cholesteryl ester transfer protein (CETP) gene is a frequent cause of
      CETP deficiency characterized by markedly increased HDL cholesterol. The
      resulting abnormalities responsible for null CETP deficiency were studied in
      detail. The CETP mRNA transcripts amplified by polymerase chain reaction from the
      monocyte-derived macrophages of two homozygous patients were both found to be
      normal except for the whole deletion of exon 14. The deletion causes a shift of
      reading frame and introduces a premature termination codon downstream.
      Examination of the macrophage RNA from heterozygotes suggested the increased
      instability of the abnormal mRNA in the cytoplasm, because the amount of the
      aberrant transcript was nearly one third that of a normal transcript in the
      cytoplasm, while they were equal in the nucleus. Although this indicated the
      synthesis of a mutant CETP that lacks about 15% at its carboxy terminus,
      immunoblot analysis demonstrated that the abnormal CETP was virtually absent in
      both the media and cell lysates of transfected COS-1 cells, which massively
      expressed the mutant CETP mRNA. These results elucidate the primary abnormality
      due to the common CETP splicing mutation to be the exon skipping of mRNA, which
      decreases the level of mRNA and produces a truncated protein that should be
      rapidly degraded intracellularly.

PMID- 9261269
TI  - Lipoprotein kinetics in patients with analbuminemia. Evidence for the role of
      serum albumin in controlling lipoprotein metabolism.
AB  - In vitro data suggested that albumin is a key factor controlling apolipoprotein
      (apo) synthesis by hepatocytes. Studies in analbuminemic rats have shown an
      increase in secretion of apoB-containing lipoprotein from the liver. We studied
      the kinetic aspects of apoB- and apoAI-containing lipoprotein metabolism in two
      sisters with analbuminemia using a constant 14-hour infusion of leucine labeled
      with stable isotopes. Compared with control subjects, total cholesterol was
      higher in the two patients (432 and 461 versus 155 +/- 14 mg/dL), as was apoB
      (257 and 230 versus 72 +/- 7 mg/dL). Triglycerides were slightly increased (134
      and 105 versus 89 +/- 9 mg/dL), whereas apoAI was lower (109 and 105 versus 124
      +/- 6 mg/dL). VLDL-apoB production was higher, as was the production of IDL-apoB
      and LDL-apoB (32.8 and 36.0 versus 24.8 +/- 5.9, 32.1 and 27.2 versus 16.4 +/-
      2.3, and 14.1 and 17.6 versus 10.3 +/- 1.2 mg.kg-1.d-1, respectively). The
      fractional catabolic rate of all the apoB-containing lipoproteins was decreased
      (0.23 and 0.37 versus 0.48 +/- 0.05, 0.27 and 0.28 versus 0.62 +/- 0.08, and
      0.012 and 0.009 versus 0.022 +/- 0.002.h-1, respectively). A similar mechanism
      could explain the dyslipidemia observed in other conditions associated with low
      albumin levels, such as nephrotic syndrome.

PMID- 9261271
TI  - Molecular basis of fish-eye disease in a patient from Spain. Characterization of
      a novel mutation in the LCAT gene and lipid analysis of the cornea.
AB  - The genetic and biochemical basis of fish-eye disease (FED) was investigated in a
      63-year-old female proband with low plasma HDL cholesterol. Analyses of corneal
      and plasma lipids of the proband were consistent with impaired
      lecithin:cholesterol acyltransferase (LCAT) activity. Free cholesterol and
      phospholipid levels were elevated relative to control values, whereas cholesteryl
      ester levels were greatly reduced. Fatty acid compositions of corneal lipids from
      the proband and control subjects differ from the respective fatty acid
      compositions of their plasma lipids. This suggests that the metabolic pathways
      and acyl chain specificities for phospholipid, cholesteryl ester, and
      triglyceride metabolism within the cornea are distinct from those of plasma.
      Sequencing of the LCAT gene from the proband revealed a novel mutation at
      nucleotide 399, corresponding to an Arg99-->Cys substitution. Secretion of LCAT
      (Arg99-->Cys) by transfected COS-6 cells was approximately 50% of that of the
      wild type, but its specific activity against reassembled HDL was 93% lower than
      that of wild-type LCAT. The specific activities of wild-type and LCAT (Arg99-
      >Cys) against LDL were reduced similarly, suggesting that the appearance of the
      FED phenotype does not require enhanced activity against LDL. Our data support
      the hypothesis that FED is a partial LCAT deficiency in which poor esterification
      in specific types of HDL particles may contribute to the appearance of the
      corneal opacities.

PMID- 9261272
TI  - Familial moderate hypercholesterolemia caused by Asp235-->Glu mutation of the LDL
      receptor gene and co-occurrence of a de novo deletion of the LDL receptor gene in
      the same family.
AB  - We identified a large family in which a hitherto unreported point mutation of the
      LDL receptor gene (Asp235-->Glu) cosegregated with moderately elevated serum LDL
      cholesterol concentration. Within one generation, the mean serum total and LDL
      cholesterol levels in four heterozygous carriers of this mutation (7.76 +/- 1.46
      and 5.89 +/- 1.56 mmol/L, respectively) were significantly (P < .05) higher than
      the corresponding concentrations in their five nonaffected siblings (5.81 +/-
      0.57 and 3.77 +/- 0.54 mmol/L, respectively). Lipid levels in carriers of the
      Asp235-->Glu mutation were, however, markedly lower than the corresponding total
      and LDL cholesterol levels (about 12 and 10 mmol/L, respectively) in heterozygous
      patients with the two common LDL receptor mutations (FH-Helsinki and FH-North
      Karelia). None of the four siblings in the age range of 54 to 69 years had
      experienced a myocardial infarction, although symptoms suggestive of coronary
      artery disease were present in two and tendon xanthomas were found in one.
      Expression of the mutant receptor in COS cells indicated an approximately 50% to
      70% reduction of LDL-binding activity compared with the normal receptor. One
      patient (female, aged 39 years) had severe hypercholesterolemia in the range of
      13 to 20 mmol/L when untreated, extensive coronary artery disease as demonstrated
      by angiography, and extensor tendon xanthomatosis. In addition to the Asp235-
      >Glu mutation, she was found to have a de novo deletion of exons 14 and 15 in her
      other LDL receptor allele. In this subject, the total LDL receptor activity of
      mitogen-stimulated blood lymphocytes was very low. In conclusion, along with
      another LDL receptor gene mutation (FH-Espoo or deletion of exon 15) described by
      us previously, the Asp235-->Glu mutation (designated as FH-Keuruu) indicates that
      moderate varieties of inherited hypercholesterolemia may result from LDL receptor
      gene mutations of mild expression.

PMID- 9261273
TI  - Therapeutic response to medium-chain triglycerides and omega-3 fatty acids in a
      patient with the familial chylomicronemia syndrome.
AB  - We have studied the underlying molecular defect in a patient presenting with
      recurrent pancreatitis, hypertriglyceridemia, and virtually undetectable
      postheparin plasma lipoprotein lipase (LPL) mass and activity, who normalized her
      triglycerides 3 to 6 months after initiation of either medium-chain triglyceride
      (MCT) oil or omega-3 fatty acid (omega-3-FA) therapy. After treatment,
      postheparin plasma LPL activity and mass ranged from 24% to 39% of normal and LPL
      specific activity was normal (1.0 nmol.ng-1.min-1). On discontinuation of MCT oil
      or omega-3-FA, plasma triglyceride increased to > 2000 mg/dL. Northern blotting
      revealed both normal size and abundance of LPL mRNA isolated from adipocytes as
      well as macrophages. Sequence analysis of the LPL gene, which included all 10
      exons, intron-exon splice junctions, and 1.7 kb of the 5'-flanking region, and of
      LPL cDNA failed to identify any mutations. ApoC-II activity and mass assays
      revealed the presence of normal levels of a fully functional cofactor as well as
      the absence of circulating plasma inhibitors of lipase function. In summary, we
      describe a unique patient presenting with classical features of the familial
      chylomicronemia syndrome who manifests an unusually beneficial therapeutic
      response to MCT oil and omega-3-FA therapy. Unlike that in most patients with LPL
      deficiency, the chylomicronemia in this patient is not caused by a mutation in
      the structural LPL gene but possibly by a posttranscriptional defect. Thus, a
      subset of LPL-deficient patients with unique genetic defects respond to therapy
      by normalizing fasting plasma triglycerides; a therapeutic trial with MCT oil
      should be considered in all patients presenting with the familial chylomicronemia
      syndrome.

PMID- 9261274
TI  - Uptake of chylomicrons by the liver, but not by the bone marrow, is modulated by
      lipoprotein lipase activity.
AB  - We have shown that chylomicrons are catabolized by the liver and bone marrow in
      rabbits and marmosets. In the present investigation, we studied the role of
      various apolipoproteins and lipoprotein lipase in the clearance of these
      particles by the liver and bone marrow in rabbits. Incubation of chylomicrons
      with purified apolipoprotein (apo) E or C-II resulted in more rapid clearance of
      these particles from the plasma, whereas incubation of chylomicrons with apoA-I,
      apoC-I, apoC-III1, or apoC-III2, did not affect their clearance rates. Analysis
      of tissue uptake revealed that the increased plasma clearance rate of
      chylomicrons enriched with apoE or apoC-II was primarily due to enhanced uptake
      by the liver. The uptake of chylomicrons by the bone marrow increased after their
      enrichment with apoA-I but decreased after their enrichment with apoC-II. Because
      apoC-II is a cofactor for lipoprotein lipase, we hypothesized that the increased
      clearance rates were due to faster hydrolysis of chylomicrons and rapid
      generation of chylomicron remnants. To test this hypothesis, lipoprotein lipase
      activity was inhibited by injection of an antilipoprotein lipase monoclonal
      antibody. Inhibition of lipoprotein lipase retarded clearance of chylomicrons
      from the plasma and decreased their uptake by the liver but did not affect their
      uptake by the bone marrow. These studies suggest that bone marrow can take up
      chylomicrons in the absence of lipoprotein lipase activity and provide an
      explanation for the presence of foam cells in the bone marrow of type I
      hyperlipoproteinemic patients.

PMID- 9261275
TI  - Lipoprotein lipase can function as a monocyte adhesion protein.
AB  - Lipoprotein lipase (LPL) is made by several cell types, including macrophages
      within the atherosclerotic lesion. LPL, a dimer of identical subunits, has high
      affinity for heparin and cell surface heparan sulfate proteoglycans (HSPGs).
      Several studies have shown that cell surface HSPGs can mediate cell binding to
      adhesion proteins. Here, we tested whether LPL, by virtue of its HSPG binding
      could mediate monocyte adhesion to surfaces. Monocyte binding to LPL-coated (1-25
      micrograms/mL) tissue culture plates was 1.4- to 7-fold higher than that of
      albumin-treated plastic. Up to 3-fold more monocytes bound to the subendothelial
      matrix that had been pretreated with LPL. LPL also doubled the number of
      monocytes that bound to endothelial cells (ECs). Heparinase and heparitinase
      treatment of monocytes or incubation of monocytes with heparin decreased monocyte
      binding to LPL. Heparinase/heparitinase treatment of the matrix also abolished
      the LPL-mediated increase in monocyte binding. These results suggest that LPL
      dimers mediate monocyte binding by forming a "bridge" between matrix and monocyte
      surface HSPGs. Inhibition of LPL activity with tetrahydrolipstatin, a lipase
      active-site inhibitor, did not affect the LPL-mediated monocyte binding. To
      assess whether specific oligosaccharide sequences in HSPGs mediated monocyte
      binding to LPL, competition experiments were performed by using known HSPG
      binding proteins. Neither antithrombin nor thrombin inhibited monocyte binding to
      LPL. Next, we tested whether integrins were involved in monocyte binding to LPL.
      Surprisingly, monocyte binding to LPL-coated plastic and matrix was inhibited by
      approximately 35% via integrin-binding arginine-glycine-aspartic acid peptides.
      This result suggests that monocyte binding to LPL was mediated, in part, by
      monocyte cell surface integrins. In summary, our data show that LPL, which is
      present on ECs and in the subendothelial matrix, can augment monocyte adherence.
      This increase in monocyte-matrix interaction could promote macrophage
      accumulation within arteries.

PMID- 9261276
TI  - Evidence for prolonged cell-surface contact of acetyl-LDL before entry into
      macrophages.
AB  - Acetyl-LDL stimulates acyl-CoA:cholesterol acyltransferase (ACAT) much more
      effectively than LDL in mouse peritoneal macrophages. Previous work with another
      potent ACAT stimulator, beta-VLDL, suggested that atherogenic lipoproteins may
      use internalization pathways distinct from that of LDL. Brief incubation of
      fluorescently labeled acetyl-LDL and LDL followed by a short chase period without
      lipoproteins was used to compare endocytic pathways. LDL was delivered rapidly to
      perinuclear vesicles, corresponding to late endosomes and lysosomes. A
      substantial fraction (> 40%) of acetyl-LDL was initially retained in the cell
      periphery, while the rest was rapidly delivered to late endosomes that also
      contained LDL. Fluorescence of peripheral 1,1'-dioctadecyl-3,3,3', 3'
      tetramethylindocarbocyanine perchlorate (DiI)-acetyl-LDL could be quenched by
      TNBS, indicating accessibility of the peripheral acetyl-LDL to the extracellular
      space. Quantification of fluorescence intensities demonstrated that > 40% of the
      cell-associated DiI-acetyl-LDL but only about 10% of DiI-LDL fluorescence was
      quenchable by TNBS after a 3-minute chase. Fucoidin can efficiently displace DiI
      acetyl-LDL bound to cells at 0 degree C. DiI-acetyl-LDL in the TNBS-quenchable
      peripheral compartments, however, was resistant to fucoidin. Electron microscopy
      of colloidal gold-acetyl-LDL showed that acetyl-LDL on the cell surface was often
      associated with microvilli or ruffles. After clearance from the surface, the
      peripheral acetyl-LDL was also delivered to the late endosomes and lysosomes.
      These results indicate that a substantial portion of acetyl-LDL enters
      macrophages through a pathway that initially differs from that of LDL. This
      pathway involves a prolonged retention of acetyl-LDL on the plasma membrane. This
      surface retention may affect ACAT activation in macrophages.

PMID- 9261277
TI  - Increased oxidation of LDL in patients with coronary artery disease is
      independent from dietary vitamins E and C.
AB  - There is increasing experimental evidence that oxidation of LDL plays a major
      role in the pathogenesis of coronary artery disease (CAD). However, results from
      clinical studies on LDL oxidation and CAD are not consistent. In most studies
      only single plasma factors of LDL oxidation have been determined. We studied 207
      patients who underwent coronary angiography. They were divided into subjects with
      CAD (n = 137) and those without CAD (n = 70). We determined the susceptibility of
      LDL to in vitro oxidation (lag phase), potential prooxidative and antioxidative
      plasma factors (plasma vitamin E, LDL vitamin E, ascorbate, iron, copper,
      ferritin, and ceruloplasmin), and markers of in vivo LDL oxidation
      (autoantibodies to malondialdehyde-modified LDL, oxidized LDL, and thiobarbituric
      acid-reactive substances), plasma lipids and lipoproteins, smoking habits, and
      other coronary risk factors in both groups. The lag phase was significantly
      shorter in patients with CAD than in patients without CAD (101 +/- 38.6 versus
      119 +/- 40.6 minutes, P < .01). There was no correlation between the lag phase
      and the other oxidation parameters or the coronary risk factors. In multivariate
      regression analyses the lag phase remained significant in all tested models. Our
      data suggest that a short lag phase of LDL oxidation might be an independent risk
      factor of CAD.

PMID- 9261278
TI  - Vitamin E/lipid peroxide ratio and susceptibility of LDL to oxidative
      modification in non-insulin-dependent diabetes mellitus.
AB  - The presence of conventional risk factors cannot sufficiently account for the
      excess risk of atherosclerosis in patients with non-insulin-dependent diabetes
      mellitus (NIDDM). Oxidative modification of LDL has been implicated in the
      pathogenesis of coronary atherosclerosis. Thirty-five patients with NIDDM, 20
      nondiabetic, hypertriglyceridemic subjects (HTG-control), and 21 diabetic,
      normotriglyceridemic subjects (NTG-control) were enrolled in this study.
      Oxidative susceptibility of LDL was determined by monitoring formation of
      conjugated dienes. Mean lag time of LDL oxidation and vitamin E/lipid peroxide of
      LDL was lower in patients with NIDDM (43.2 +/- 3.9 minutes and 1.6 +/- 1.3) than
      in HTG-control (48.8 +/- 3.2 minutes and 2.3 +/- 1.2, respectively) and NTG
      control subjects (54.2 +/- 6.1 minutes and 3.0 +/- 1.8, respectively). Mean LDL
      particle size in patients with NIDDM and HTG-control subjects (24.4 +/- 0.9 and
      24.7 +/- 0.7 nm, respectively) was smaller than in NTG-control subjects (25.9 +/-
      1.0 nm). Multiple stepwise regression analyses ascertained that the vitamin.
      E/lipid peroxide of LDL is a major determinant of LDL oxidation lag time. These
      results suggest that LDL in patients with NIDDM is more susceptible to oxidative
      modification primarily because of a reduced level of vitamin E/lipid peroxide of
      LDL. The enhanced susceptibility of LDL to oxidation may be a pivotal factor
      underlying the increased incidence of vascular disease in patients with NIDDM.

PMID- 9261279
TI  - Relationship of LDL size to insulin sensitivity in normoglycemic men.
AB  - A preponderance of small, dense LDL has been suggested to be more atherogenic
      than larger, more buoyant LDL. Although several studies have suggested
      associations of small, dense LDL with hyperinsulinemia, few data are available on
      the relation of small, dense LDL to insulin resistance. We examined the
      association of LDL particle size determined by gradient gel electrophoresis with
      the rates of whole-body glucose uptake (WBGU) as determined by the
      hyperinsulinemic euglycemic clamp with indirect calorimetry in 87 Finnish
      normoglycemic men. LDL size was significantly positively correlated with the
      rates of WBGU (overall, r = .31, P < .01; oxidative, r = .23, P < .05; and
      nonoxidative, r = .31, P < .01). Rates of WBGU were also significantly lower in
      subjects with small LDL particles (< or = 26.0 nm) compared with those in
      subjects with larger LDL particles (> 26.0 nm). This relation was not explained
      by obesity. Serum triglyceride concentrations were found to significantly affect
      the relationship of LDL particle size to WBGU. Specifically, LDL size was
      correlated with the rates of WBGU in men with mildly elevated triglyceride levels
      but not in men with low triglyceride levels. Serum VLDL triglyceride
      concentration was a substantially stronger determinant of LDL size than were the
      rates of WBGU. WBGU was not significantly related to LDL size when adjusted for
      triglycerides. We conclude that a preponderance of small, dense LDL particles is
      associated with insulin resistance and that serum triglyceride concentration
      modifies this relationship.

PMID- 9261280
TI  - Metabolic basis of hypotriglyceridemic effects of insulin in normal men.
AB  - The mechanism by which acute insulin administration alters VLDL apolipoprotein
      (apo) B subclass metabolism and thus plasma triglyceride concentration was
      evaluated in 7 normolipidemic healthy men on two occasions, during a saline
      infusion and during an 8.5-hour euglycemic hyperinsulinemic clamp (serum insulin,
      490 +/- 30 pmol/L). During the insulin infusion, plasma triglycerides decreased
      by 22% (P < .05), and serum free fatty acid decreased by 85% (P < .05). The
      plasma concentration of VLDL1 apo B fell 32% during the insulin infusion, while
      that of VLDL2 apo B remained constant. A bolus injection of [3-(2)H]leucine was
      given on both occasions to trace apo B kinetics in the VLDL1 and VLDL2 subclasses
      (Svedberg flotation rate, 60-400 and 20-60, respectively), and the kinetic basis
      for the change in VLDL levels caused by insulin was examined using a non-steady
      state multicompartmental model. The mean rate of VLDL1 apo B synthesis decreased
      significantly by 35% (P < .05) after 0.5 hour of the insulin infusion (523 +/- 87
      mg/d) compared with the saline infusion (808 +/- 91 mg/d). This parameter was
      allowed to vary with time to explain the fall in VLDL1 concentration. After 8.5
      hours of hyperinsulinemia, the rate of VLDL1 apo B synthesis was 51% lower (321
      +/- 105 mg/d) than during the saline infusion (651 +/- 81 mg/d, P < .05). VLDL2
      apo B production was similar during the saline (269 +/- 35 mg/d) and insulin (265
      +/- 37 mg/d) infusions. No significant changes were observed in the fractional
      catabolic rates of either VLDL1 or VLDL2 apo B. We conclude that acute
      hyperinsulinemia lowers plasma triglyceride and VLDL levels principally by
      suppressing VLDL1 apo B production but has no effect on VLDL2 apo B production.
      These findings indicate that the rates of VLDL1 and VLDL2 apo B production in the
      liver are independently regulated.

PMID- 9261281
TI  - Nonobese patients with familial combined hyperlipidemia are insulin resistant
      compared with their nonaffected relatives.
AB  - Familial combined hyperlipidemia (FCH) is a heterogeneous lipid disorder, caused
      by overproduction of VLDL and characterized by the occurrence of small, dense LDL
      particles, all features that are also associated with insulin resistance.
      Therefore, insulin sensitivity was examined directly by means of the euglycemic
      hyperinsulinemic clamp technique in male nonobese, normotensive FCH patients and
      compared with that of their nonaffected relatives, matched for age and body mass
      index (BMI). In addition, an oral 75-g glucose tolerance test (OGTT) was
      performed and lipid values, including the LDL subfraction profile, were
      determined. During the clamp, forearm blood flow (FBF) was measured by venous
      occlusion plethysmography. All participants had a normal glucose response after
      the glucose load, whereas FCH patients showed hyperinsulinemia after OGTT and
      higher fasting C-peptide levels. During the clamp, insulin concentrations
      increased equally in both groups. Mean whole-body glucose uptake (M) (120 to 180
      minutes) was lower in FCH patients than in nonaffected relatives (6.89 +/- 0.31
      versus 8.94 +/- 0.76 mg.kg-1.min-1; P = .01). In addition, the glucose uptake per
      unit insulin (I) was lower in FCH patients (insulin sensitivity index [M/I], 7.46
      +/- 0.50 versus 9.51 +/- 0.53; P = .009). M significantly correlated with BMI,
      plasma cholesterol and triglyceride concentrations, and the individual LDL
      density. The FBF correlated with insulin sensitivity and increased significantly
      in nonaffected relatives (1.9 +/- 0.12 to 2.5 +/- 0.4 mL.min-1.dL-1; P = .025)
      but not in patients. Thus, FCH patients characterized by a predominance of small,
      dense LDL are insulin resistant compared with their nonaffected relatives. This
      insulin resistance may partly be explained by a decreased insulin-induced
      vasodilation in skeletal muscle.

PMID- 9261282
TI  - Sex differences in visceral fat lipolysis and metabolic complications of obesity.
AB  - Cardiovascular complications of obesity are more common in men than women. Sex
      differences in visceral fat lipolysis may be of importance in this respect, since
      increased release of free fatty acids (FFAs) from visceral fat to the liver by
      the portal venous system has been thought to cause several metabolic
      complications due to obesity, such as hypertension, hyperlipidemia, and glucose
      intolerance. The aim of this study was to investigate sex differences in clinical
      characteristics and visceral fat mobilization in obesity. Obese subjects (22 male
      and 23 female) undergoing elective surgery were matched for body mass index and
      age. The males had both higher waist-to-hip ratio (WHR), sagittal diameter, blood
      pressure, fat-cell volume, plasma insulin, glucose, and triglyceride and lower
      HDL cholesterol levels than the females. The rate of norepinephrine-induced FFA
      and glycerol release was twofold higher in men (P = .02). No significant
      reutilization of FFA was observed. The difference in maximum norepinephrine
      induced rate of lipolysis between men and women was independent of both WHR and
      sagittal diameter and was an independent regressor for levels of plasma glucose
      and plasma HDL cholesterol. Fat-cell volume was an independent regressor for
      plasma triglycerides and blood pressure. No sex differences in the lipolytic
      sensitivity to beta 1- or beta 2-adrenoceptor-specific agonists or in the
      antilipolytic effect of insulin were observed. However, the lipolytic beta 3
      adrenoceptor sensitivity was 12 times higher (P = .004) and the antilipolytic
      alpha 2-adrenoceptor sensitivity 17 times lower (P = .003) in men. Furthermore,
      lipolysis induced by agents acting at the adenylate cyclase and protein kinase A
      levels were almost twofold enhanced in men. However, no sex difference in maximum
      hormone-sensitive lipase activity was observed. In conclusion, in obesity,
      catecholamine-induced rate of FFA mobilization from visceral fat to the portal
      venous system is higher in men than women. This phenomenon is partly due to a
      larger fat-cell volume but also to a decrease in the function of alpha 2
      adrenoceptors, an increase in the function of beta 3-adrenoceptors, and an
      increased ability of cyclic AMP to activate hormone-sensitive lipase. These
      factors may contribute to gender-specific differences in metabolic and
      cardiovascular disturbances accompanied by obesity.

PMID- 9261283
TI  - Insecure about Social Security. Part 1: How the system works and what is being
      assumed about its uncertain future.

PMID- 9261284
TI  - Keeping an eye on vision: primary care of age-related ocular disease. Part 1.
AB  - Normal changes in the lens, retina, and vitreous accompany aging, but loss of
      vision in late life is not an inevitable consequence of aging. Cataract,
      glaucoma, diabetic retinopathy, and age-related macular degeneration (ARMD)
      account for most vision loss in the older population. Visual impairment reduces
      older patients' ability to function independently and increases their risk of
      depression and of injury due to falls. When older persons have a visual
      complaint, they tend to blame it on being old and do not tell their physicians.
      In the primary care office, simple screening questions and examination of the
      dilated eye can often reveal a need for further examination and/or referral.

PMID- 9261285
TI  - Meningitis in older patients: how to diagnose and treat a deadly infection.
AB  - Studies of bacterial meningitis have documented a peak of incidence among persons
      age 60 and older. The most common bacterial pathogens in these patients differ
      from those seen in children. Presentation of meningitis in older patients may be
      atypical; fever is not a consistent finding, and nonspecific symptoms such as
      confusion are often seen. Nuchal rigidity is not as sensitive nor as specific a
      sign as in younger patients. Definitive diagnosis relies on interpretation of CSF
      studies. Ampicillin plus a third-generation cephalosporin should be administered
      for community-acquired meningitis until Gram's stain and culture results return.
      Cases of S pneumoniae meningitis may require varying strategies, based upon the
      degree of penicillin resistance.

PMID- 9261286
TI  - Care of the skin at midlife: diagnosis of pigmented lesions.
AB  - Intrinsic skin changes with advancing years include dryness, decreasing
      elasticity, increasing skin fragility, and more prominent vasculature. Extrinsic
      skin aging, caused primarily by cigarette smoking and exposure to sunlight,
      includes mottled pigmentation and yellow discoloration, rough leathery textural
      changes, and wrinkling. Major premalignant and malignant neoplasms in
      photodamaged skin are actinic keratosis, basal cell carcinoma, squamous cell
      carcinoma, and melanoma. Nonmalignant lesions include solar lentigines and
      seborrheic keratoses. The A, B, C, D criteria can assist in the evaluation of
      pigmented nevi. Physicians play an important role in educating patients about the
      health risks associated with excessive sun exposure and about sun protection to
      prevent further skin damage.

PMID- 9261287
TI  - Strategies to protect bone mass in the older patient with epilepsy.
AB  - The annual incidence of epileptic seizures rises dramatically after the age of
      60. Risk factors associated with late-onset epilepsy include cerebrovascular
      disease, dementia, infection, trauma, and alcoholism. The dominant cause of
      seizures in older patients is a previous stroke, whereas a significant percentage
      of cases are attributed to the presence of a tumor. Normal aging is associated
      with an increased risk for fractures from trauma and osteoporosis. Antiepileptic
      medications may exacerbate this problem by adversely affecting bone metabolism
      and increasing the risk of falls related to drug toxicity. The patient work-up,
      careful prescribing, and monitoring for drug toxicity can help preserve bone
      integrity in patients receiving antiepileptic drug therapy.

PMID- 9261288
TI  - Periurethral abscess: complication of UTI.

PMID- 9261289
TI  - The 'good' death: three promises to make at the bedside.

PMID- 9261290
TI  - Multiple red lesions on the legs.

PMID- 9261291
TI  - Cardiovascular function during cognitive stress in men before and after coronary
      artery bypass grafts.
AB  - Cardiovascular function during cognitive stress using the Stroop Color Test
      (SCWT) was documented in 25 men with ischemic heart disease (IHD) before and
      after coronary artery bypass grafting (CABG). Impedance cardiography was used to
      measure changes from resting baseline in heart rate (HR), stroke volume (SV),
      cardiac output (CO), myocardial contractility, and total peripheral resistance
      (TPR). Cognitive stress was associated with significant increases in HR, blood
      pressure, SV, CO, and myocardial contractility. TPR did not change from resting
      baseline during cognitive stress before CABG. However, TPR decreased
      significantly from resting baseline during cognitive stress after CABG. These
      findings support the theory that cognitive stress is associated with a
      significant increase in myocardial oxygen demand.

PMID- 9261292
TI  - Effect of short-duration hyperventilation during endotracheal suctioning on
      intracranial pressure in severe head-injured adults.
AB  - A repeated measures randomized within-group design was used to determine the
      effectiveness of controlled short-duration hyperventilation (HV) in blunting the
      increase of intracranial pressure (ICP) during endotracheal suctioning (ETS). A
      multimodal continuous real-time computerized data acquisition procedure was used
      to compare the effects of two HV ETS protocols on ICP, arterial pressure,
      cerebral perfusion pressure (CPP), heart rate, and arterial oxygen saturation in
      severe head-injured adult patients. The results indicated that short-duration HV
      for 1 minute, which decreases the PaCO2, reduced ETS-induced elevations in ICP
      while maintaining CPP. However, it is not clear whether short-duration HV is
      neuroprotective, particularly in ischemic regions of the brain. Therefore, before
      a change in practice is implemented on the use of short-duration HV as a
      prophylactic treatment against ETS-induced elevations in ICP, additional
      questions on cerebral oxygen delivery and uptake need to be answered.

PMID- 9261293
TI  - The effect of environment on body site temperatures in full-term neonates.
AB  - The effect of environment on temperature was examined by comparing tympanic,
      rectal, inguinal, and axillary temperatures for 63 term infants in three
      environments: incubator, bassinet, and radiant warmer. Tympanic temperatures were
      collected with a FirstTemp (Intelligent Medical Systems, Carlsbad, CA) infrared
      thermometer in the cal-tympanic mode. Rectal, inguinal, and axillary temperatures
      were collected with an IVAC digital thermometer (San Diego, CA) in the predictive
      mode. There were moderate correlations between the body site temperatures. The
      environment significantly influenced temperature readings at the different sites.
      Temperatures assessed in the superheated environments of the radiant warmer and
      the incubator were consistently higher than temperatures in the bassinet.

PMID- 9261294
TI  - Validation of the structure for the "Clinical Assessment of Confusion-A".
AB  - The Clinical Assessment of Confusion-A (CAC-A) is an observational checklist
      developed for practicing nurses to measure the presence and level of confusion in
      hospitalized adults. In a previous study, the following dimensions were found
      using principal factor analysis: cognition, general behavior, motor activity,
      orientation, psychotic/neurotic behavior, and two uninterpretable factors. A
      replication study was conducted to evaluate the validity of a statistically
      derived model for confusion suggested by the CAC-A. Data from a sample of 566
      nurses were analyzed. Three theoretically justified statistical models for the
      structure of confusion were estimated and compared using a model selection
      approach to covariance structures analysis: a single-factor unidimensional model,
      an orthogonal six-factor model, and an oblique six-factor model similar to the
      structure suggested in the development study. The oblique six-factor model
      provided the best fit in the predictive sense and was the most satisfactory from
      a theoretical perspective.

PMID- 9261295
TI  - Depressive phenomena, physical symptom distress, and functional status among
      women with breast cancer.
AB  - The nature and scope of depression and its relationship to physical symptom
      distress and functional status were examined in 79 women 3 to 7 months after
      breast cancer diagnosis. Psychiatric diagnostic criteria for depressive disorders
      and a depression rating scale were used to measure depression. Nine percent of
      the sample had depressive disorder, and 24% had elevated depressive symptoms.
      Women with elevated depressive symptoms had more physical symptom distress (p <
      .0001) and more impaired functioning (p < .0001) than subjects with depressive
      disorders and without depression. Multiple regression was used to examine the
      contribution of key variables to functional status. Two variables accounted for
      35% of the variance in functional status: symptom distress (28%) and depressive
      symptoms (7%).

PMID- 9261296
TI  - Progress in the moral reasoning of baccalaureate nursing students between program
      entry and exit.
AB  - Changes in moral reasoning between entry into and exit from a baccalaureate
      nursing program and the relationship between student characteristics and moral
      reasoning at entry and exit were explored in this descriptive study. The moral
      reasoning of four cohorts of students was measured using the Defining Issues Test
      (DIT). Admission grade point average, prior college credits, and gender accounted
      for 10% of the variance in DIT P% scores at entry and 14% of the variance at exit
      from the program. Female students had significantly higher moral reasoning scores
      than men. Age did not contribute significantly to explaining DIT score variance.
      DIT P% scores at entry for all four cohorts were within the range of reported
      norms for college students. Exit scores for all four cohorts were between the
      normative means for undergraduate students and graduate students. DIT P% score
      gains between entry and exit were significant for all four cohorts. Students
      whose entry scores were in the lowest categories had the greatest mean gains.

PMID- 9261297
TI  - Comparison of three methods of data collection in an urban Spanish-speaking
      population.

PMID- 9261298
TI  - Correspondence analysis: a graphical technique for examining categorical data.

PMID- 9261299
TI  - Where reality meets methodology in conducting nursing intervention research with
      women.

PMID- 9261300
TI  - Unilateral retinoblastoma in adults.

PMID- 9261301
TI  - Noninvasive closure of persistent cyclodialysis cleft.

PMID- 9261302
TI  - Scleritis-associated uveitis.

PMID- 9261303
TI  - Primary glaucoma triple procedure.

PMID- 9261304
TI  - Complications of small clear-zone radial keratotomy.

PMID- 9261305
TI  - Pointers on laser pointers.

PMID- 9261306
TI  - Needling versus medical treatment in encapsulated blebs. A randomized,
      prospective study.
AB  - OBJECTIVE: The purpose of the study is to compare the efficacy and safety of
      transconjunctival needling and medical treatment in eyes with encapsulated blebs.
      DESIGN: A randomized, prospective study. PARTICIPANTS: Two hundred eighty-two
      eyes that underwent a guarded filtration procedure between January 1994 and
      January 1996 at the Glaucoma Service of University of Campinas. INTERVENTION:
      Encapsulated blebs developed in 25 (8.9%) of 282 eyes and were randomized to
      either needling (n = 14) or medical treatment with aqueous humor suppressants (n
      = 11). If one treatment failed to maintain intraocular pressures (IOPs) below 20
      mmHg, the other treatment was initiated. If both methods failed, surgical
      revision or further glaucoma surgery was performed. Complete success was defined
      as IOP less than 20 mmHg after one treatment method. Qualified success was
      defined when IOPs less than 20 mmHg were obtained with both treatment methods,
      whereas failure was defined when IOP greater than 20 mmHg or when further surgery
      was indicated. MAIN OUTCOME MEASURES: Intraocular pressure, vision, and number of
      antiglaucoma medications. RESULTS: After a mean follow-up of 9.6 months, medical
      treatment alone was successful in ten patients (90.9%), whereas needling alone
      was successful in one patient (7.1%) (P = 0.00003). In the needling group, 92.9%
      of the eyes required aqueous humor suppressants, and 57.1% were considered
      qualified successes at the last follow-up (mean = 10.1 months). At the last
      follow-up examination, there was no statistically significant difference between
      the mean number of medications in both groups (P = 0.797). Further glaucoma
      surgery was performed in five patients (35.7%) undergoing needling and one
      patient (9.1%) receiving medical treatment (P = 0.162). CONCLUSIONS: Medical
      treatment with digital pressure should be used as the initial treatment in eyes
      with encapsulated blebs. Needling procedures or surgical revision, methods that
      are more invasive and potentially associated with severe complications, should be
      limited to the small percentage of eyes that do not respond to medical treatment.

PMID- 9261307
TI  - The effect of phacoemulsification on aqueous outflow facility.
AB  - OBJECTIVE: Although control of intraocular pressure (IOP) after cataract
      extraction may be of critical importance, little is known regarding changes in
      facility of outflow in the early postoperative period. The effect of
      phacoemulsification and conjunctival peritomy size on the coefficient of aqueous
      outflow facility (C) and IOP was studied. DESIGN: Participants were assigned
      randomly to one of two treatment groups. PARTICIPANTS: Seventy-four patients with
      cataract and without evidence of glaucoma were studied. INTERVENTION: Patients
      were randomized to receive either single- or two-quadrant conjunctival peritomy
      and phacoemulsification. MAIN OUTCOME MEASURES: Tonometry and tonography were
      assessed before surgery and at 1 day, 1 week, 6 weeks, and 1 year after surgery
      by a masked observer. RESULTS: Fifty patients with a mean of 11.4 months' (range,
      10-13 months) follow-up were analyzed. Patients with reduced preoperative
      facility of outflow (as defined by C < or = 0.28 microliter/min/mmHg) showed a
      significant improvement from a mean preoperative value of 0.24 +/- 0.04
      microliter/min/mmHg to 0.41 +/- 0.22 microliter/min/mmHg at 1 year (P = 0.002, N
      = 19). Among all patients, there was no significant change between mean
      preoperative C and last follow-up (0.39 +/- 0.23 vs. 0.46 +/- 0.38
      microliter/min/mmHg, not significant [ns], N = 50). Furthermore, there was no
      significant change between mean preoperative and final IOP (23.7 +/- 4.1 vs. 23.3
      +/- 3.9 mmHg, ns, N = 50). There was a significant elevation of mean IOP on
      postoperative day 1 to 27 +/- 6.2 mmHg (P = 0.001, N = 50). Patients with IOP
      elevations greater than 8 mmHg on postoperative day 1 had significantly elevated
      IOP at 1 year compared to preoperative values (P = 0.02, N = 12). There were no
      significant differences detected regarding C or IOP between single- or two
      quadrant peritomy groups. CONCLUSIONS: Outflow facility improves after
      phacoemulsification in patients with a reduced preoperative coefficient of
      aqueous outflow. Postoperative day 1 IOP is significantly elevated after
      phacoemulsification. Conjunctival peritomy size does not appear to play a role in
      aqueous outflow facility or IOP after surgery.

PMID- 9261309
TI  - Small incision trabeculectomy avoiding Tenon's capsule. A new procedure for
      glaucoma surgery.
AB  - BACKGROUND AND PURPOSE: Wound healing at the level of Tenon's capsule is a common
      cause of trabeculectomy failure. The purpose of this study is to present a new
      technique for glaucoma filtering surgery in which an injury to Tenon's capsule is
      minimized. METHODS: A 2.5-mm conjunctival peritomy was performed without cutting
      Tenon's capsule. A partial-thickness incision was made at the limbus and a
      scleral pocket was dissected 2 to 3 mm posteriorly. The subconjunctival space was
      entered with a cystotome passed through the scleral pocket, and balanced salt
      solution (BSS, Alcon Laboratories, Ft. Worth, TX) was injected, forming a
      subconjunctival bleb. In patients considered high risk, 5-fluorouracil (5 mg) was
      mixed with the BSS injected. The anterior chamber was entered at the initial
      limbal incision. A 1.5- by 1-mm fragment of the floor of the pocket was excised,
      followed by a peripheral iridectomy. The scleral wound, as well as the
      conjunctiva, was closed with separate 10-0 nylon sutures. This procedure was
      performed in 30 glaucomatous eyes. Seven high-risk eyes received four to seven
      postoperative injections of 5 mg of 5-fluorouracil. RESULTS: Preoperative
      intraocular pressure (IOP) was 34.5 +/- 8.1 mmHg. Postoperative IOP was 13.2 +/-
      4.1 at 6 months (P < 0.01), and 90% of the eyes had IOP less than or equal to 18
      mmHg without medication. Mean follow-up was 7.6 months (range, 6-14 months).
      Blebs were low-lying and diffuse. No serious complications were encountered.
      CONCLUSIONS: This new technique is a safe procedure that effectively reduces IOP.
      It is done through a small incision without sophisticated instruments. More cases
      and a prospective trial are needed to ascertain its potential advantages over
      those of conventional trabeculectomy.

PMID- 9261308
TI  - Comparison of methods to detect visual field progression in glaucoma .
AB  - OBJECTIVE: The purpose of the study is to develop alternative statistical
      approaches for evaluating the trend of visual field series over time and to
      compare the results to human observers. DESIGN: Retrospective analysis of visual
      field results. PARTICIPANTS: Eighty-three eyes of 83 patients (phakic or
      pseudophakic) with open-angle glaucoma and 5 or more eligible fields were
      included in the study. INTERVENTION: Three experienced observers independently
      reviewed the field series to determine stability or progression. MAIN OUTCOME
      MEASURES: The following additional methods to determine progression of visual
      field loss were used: (1) pointwise univariate regression analysis and a glaucoma
      change analysis; (2) univariate regression analysis on visual field indices mean
      deviation, corrected loss variance, and glaucoma pattern index; (3) pointwise
      multivariate regression analysis with fixed effects on panel data; and (4)
      clusterwise multivariate regression analysis with fixed effects on panel data.
      The results of different statistical methods were compared by determining the
      pairwise agreement (Cohen's weighted kappa) between each technique and three
      experienced observers. RESULTS: Patients were observed for a mean (+/-standard
      deviation) of 5.6 (+/-1.4) years. The visual fields of 27 (33%) and 56 (67%) eyes
      were considered to have progressed or remained stable, respectively, based on
      agreement of at least 2 of 3 observers. Univariate regression analysis on visual
      field indices was not useful for detection of visual field progression. Pointwise
      and clusterwise regression analyses with fixed effects on panel data performed as
      well as pointwise univariate regression analysis compared with human observers
      (kappa = 0.52, 0.53, and 0.55, respectively). Both methods showed better
      agreement with human observers than with glaucoma change analysis (kappa = 0.41).
      CONCLUSIONS: A new statistical model, multivariate regression analyses with fixed
      effects on panel data, is an appropriate method to evaluate the course of visual
      field series over time and shows reasonable agreement with experienced observers
      and pointwise univariate regression analysis.

PMID- 9261310
TI  - Photodynamic therapy and digital angiography of experimental iris
      neovascularization using liposomal benzoporphyrin derivative.
AB  - PURPOSE: To study the efficacy of liposomal benzoporphyrin derivative (BPD)
      (Verteportin) for the angiographic visualization and photodynamic therapy (PDT)
      of experimental iris neovascularization. METHODS: Experimental iris
      neovascularization was induced in eight cynomolgus monkey eyes by occluding all
      the branch retinal veins with a dye-yellow (577-nm) laser. Iris angiography was
      done with sodium fluorescein, indocyanine green (ICG), and liposomal BPD to
      compare the visualization of normal and neovascular vessels by these three dyes.
      PDT was performed using an intravenous infusion of liposomal BPD (0.375-0.75
      mg/kg), followed by irradiation with 689-nm light from a diode laser/slit-lamp
      delivery system using 600 mW/cm2 irradiance and 150 J/cm2 fluence. The effect of
      treatment was followed by iris photography and angiography, and the findings were
      confirmed by histopathology using light and electron microscopy. RESULTS: Iris
      fluorescein angiography (FA) showed superficial tortuous and leaky new vessels.
      Liposomal BPD and ICG angiography of the same eye demonstrated deeper dilated and
      tortuous iris vessels, with minimal dye leakage. PDT of the iris with
      irradiation, performed within 20 minutes of the start of dye infusion (0.75
      mg/kg), resulted in angiographic and histologic occlusion of iris vessels
      examined at 24 hours. Three to nine days after PDT, histopathologic examination
      showed regression of the iris neovascular membrane, with some open vessels.
      CONCLUSIONS: Liposomal BPD and ICG provided angiographic visualization of deeper
      normal and neovascular iris vessels. PDT using liposomal BPD leads to effective
      early closure to experimental iris neovascularization.

PMID- 9261311
TI  - Rubeosis iridis in retinoblastoma. Histologic findings and the possible role of
      vascular endothelial growth factor in its induction.
AB  - PURPOSE: Iris neovascularization (rubeosis iridis) is a common finding in eyes
      harboring retinoblastoma. The purpose of the current study is to evaluate the
      histologic factors that may affect the development of rubeosis iridis in eyes
      with retinoblastoma and to examine whether vascular endothelial growth factor
      (VEGF), a hypoxia-induced angiogenic factor, is produced by hypoxic
      retinoblastoma and retinal cells in these eyes. MATERIALS AND METHODS: One
      hundred eighty-one enucleated eyes containing retinoblastoma were the source for
      the current study. Histologic slides were evaluated for the presence and degree
      of rubeosis iridis as well as for other histologic factors. Univariate and
      multivariate statistical analyses were performed to find a correlation between
      rubeosis iridis and the other histologic factors. Eight of the eyes underwent in
      situ hybridization with a specific VEGF mRNA probe to locate tumor and retinal
      cells that may produce this hypoxia-induced angiogenic factor. RESULTS: The
      amount of tumor necrosis as well as choroidal and optic nerve invasion was found
      to be one of the most important factors that correlated with the presence and
      degree of rubeosis iridis in the examined eyes. All eight eyes that underwent in
      situ hybridization analysis showed strong signals of VEGF mRNA in retinoblastoma
      cells around necrotic regions and in the outer nuclear layers in areas of
      detached retina. CONCLUSIONS: There exists an association between rubeosis iridis
      and histologic factors found in advanced stages of retinoblastoma, especially the
      amount of tumor necrosis. Vascular endothelial growth factor may well be an
      angiogenic factor that is secreted by the hypoxic retinoblastoma and retinal
      cells and, reaching the iris, causes (presumably in collaboration with other
      factors) rubeosis iridis.

PMID- 9261312
TI  - Ciliary body and choroidal detachment after laser photocoagulation for diabetic
      retinopathy. A high-frequency ultrasound study.
AB  - OBJECTIVE: The purpose of the study is to clarify the manifestation of the
      ciliary body after retinal photocoagulation for diabetic retinopathy. DESIGN:
      Ultrasound biomicroscopy (UBM) was applied to obtain the tomographic features of
      the anterior ocular segment. PARTICIPANTS: Twenty-one eyes of 17 consecutive
      patients with diabetic retinopathy were included in this study. INTERVENTION:
      These eyes were treated by panretinal photocoagulation divided in four sessions.
      In the first session, the nasal quadrant of the fundus was treated with argon or
      dye (590 nm) laser totaling 208 to 331 spots per eye. MAIN OUTCOME MEASURES: The
      eyes were examined by UBM before, immediately after, 3, and 7 days after the
      first session of photocoagulation. RESULTS: Three days after photocoagulation,
      ciliochoroidal detachment was observed in 19 eyes (90%). The detachment was
      present along the whole circumference. The ciliary detachment was most prominent
      in the pars plana in 19 eyes and extended to the pars plicata in 9 eyes. It
      spontaneously had disappeared 7 days after photocoagulation. CONCLUSIONS:
      Ciliochoroidal detachment was a very frequent feature after sector
      photocoagulation in diabetic eyes. Although this complication was asymptomatic
      and transient so far, this potential hazard merits due attention in the planning
      of panretinal photocoagulation in diabetic eyes.

PMID- 9261313
TI  - Survey of 520 eyes with uveal metastases.
AB  - OBJECTIVE: The purpose of this investigation is to report the clinical features
      of patients with uveal metastases seen at a major ocular oncology center.
      DESIGN/PARTICIPANTS: A retrospective chart review was performed on all patients
      with uveal metastases evaluated at an ocular oncology outpatient facility over a
      20-year period. MAIN OUTCOME MEASURE: To assess the systemic and ophthalmic
      features of uveal metastases. RESULTS: A total of 950 uveal metastases were
      diagnosed in 520 eyes of 420 consecutive patients. Of the 950 metastatic foci,
      the uveal involvement included iris in 90 (9%), ciliary body in 22 (2%), and
      choroid in 838 (88%). The total number of uveal metastases per eye was 1 (71%) in
      370 eyes, 2 (12%) in 63 eyes, and 3 or more (17%) in 87 eyes. The mean number of
      uveal metastases per eye was two (median, one). Iris metastases presented most
      often as a yellow-to-white solitary nodule in the inferior quadrant. Ciliary body
      metastases typically presented as a solitary, sessile, or dome-shaped yellow mass
      in the inferior quadrant, but were difficult to visualize directly. The choroidal
      metastases typically were yellow in color, plateau shaped, and associated with
      subretinal fluid. In the 479 eyes with choroidal metastases, the epicenter of the
      main tumor was found in the macular area in 59 eyes (12%), between the macula and
      equator in 383 eyes (80%), and anterior to the equator in 37 eyes (8%). The mean
      size of the main (largest) choroidal tumor in each eye was 9 mm in base and 3 mm
      in thickness. At the time of ocular diagnosis, 278 patients (66%) reported a
      history of a primary cancer and 142 patients (34%) had no history of a cancer.
      Subsequent evaluation of these 142 patients after the ocular diagnosis of uveal
      metastasis showed a primary tumor in the lung in 50 patients (35%), breast in 10
      (7%), others in 9 (6%), and no primary site was found in 73 patients (51%).
      Nearly half of the patients with no known primary site eventually died of diffuse
      metastatic disease. In the entire group of 420 patients, the uveal metastasis
      came from a primary cancer of the breast in 196 (47%), lung in 90 (21%),
      gastrointestinal tract in 18 (4%), kidney in 9 (2%), skin in 9 (2%), prostate in
      9 (2%), and other cancers in 16 (4%). In 73 cases (17%), the primary site was
      never established despite systemic evaluation by medical oncologists.
      CONCLUSIONS: Iris, ciliary body, and choroidal metastases have typical clinical
      features that should suggest the diagnosis. The choroid is the most common site
      for uveal metastases, and the tumors occur most often in the posterior pole of
      the eye with an average of two tumors per eye. Approximately one third of
      patients have no history of primary cancer at the time of ocular diagnosis.
      Breast and lung cancers represent more than two thirds of the primary tumor
      sites.

PMID- 9261314
TI  - Incision sizes for foldable intraocular lenses.
AB  - OBJECTIVE: The purpose of the study is to determine the minimal incision sizes
      required for implantation of a variety of different foldable intraocular lenses
      (IOLs) and to evaluate the effect of incision size on tissue damage. DESIGN:
      Randomized experimental study. PARTICIPANTS: Sixty-nine fresh human cadaveric
      eyes: 15 (pilot study), 48 (main study), and 6 (scanning electron microscopy
      study). INTERVENTION: Implantation of foldable IOLs into cadaveric eyes. MAIN
      OUTCOME MEASURES: In 48 fresh human cadaveric eyes, limbal corneal tunnel
      incisions were made, and in a randomized fashion, 8 different foldable IOLs of
      20.5 diopters (D) were inserted: 4 silicone (SI-30NB, Allergan Medical Optics,
      Irvine, CA; C10UB, Chiron Ophthalmics, Inc, Irvine, CA; LI41U, IOLAB, Chiron
      Ophthalmics, Inc, Irvine, CA; AA-4203, Staar Surgical Company, Monrovia, CA); two
      soft acrylic (MA60BM and MA30BA, both Alcon Laboratories, Inc, Ft. Worth, TX);
      and two hydrogel models (SH30BC, Alcon; H60M, Storz Ophthalmics, Inc, St. Louis,
      MO). For each IOL model, six insertions were performed with a recommended
      implantation device. Using calipers, the authors measured internal and external
      incision sizes before and after insertion. Scanning electron microscopy was
      performed on selected incisions in six additional human cadaveric eyes. RESULTS:
      Incision sizes after insertion ranged from 3.2 to 3.8 mm. The smallest incisions
      permitting IOL insertion were associated with the injectors. However, these
      incisions enlarged after insertion by approximately 11% and then were similar to
      the incision sizes after forceps insertion of the high-refractive-index silicone,
      the 5.5-mm optic acrylic, and the one-piece hydrogel IOL. The largest incisions
      were associated with the 6-mm acrylic IOL and the three-piece silicone IOL with a
      lower refractive index. The scanning electron microscopy showed tearing of
      corneal tissue after implantation through the smallest incision; this was more
      pronounced with injectors than with forceps. CONCLUSIONS: Corneal tunnel
      incisions enlarged up to 11% after insertion of foldable IOLs through the
      smallest possible incision. With current technology, the smallest postinsertion
      incision size of a 20.5-D foldable IOL is 3.2 mm.

PMID- 9261315
TI  - Evaluation of visual function following neodymium:YAG laser posterior
      capsulotomy.
AB  - PURPOSE: Improvement in visual acuity is the primary endpoint for successful
      neodymium:YAG (Nd:YAG) laser posterior capsulotomy for posterior capsule
      opacification. There is limited information on related parameters of visual
      function that may also improve after laser treatment. The authors evaluate
      changes in contrast sensitivity and glare disability, aside from visual acuity,
      following Nd:YAG laser posterior capsulotomy. METHODS: Measurements of visual
      acuity, contrast sensitivity (using the Pelli-Robson chart), and glare disability
      (using the Brightness Acuity Tester [Mentor O & O, Inc., Norwell, MA]) were
      obtained from 24 consecutive patients before and after Nd:YAG laser posterior
      capsulotomy. Glare testing was done with both the Pelli-Robson and Early
      Treatment Diabetic Retinopathy Study (ETDRS) charts. The degree of glare
      disability was indicated by the difference between visual function with glare (at
      medium and high settings) and without glare. Prelaser measurements were taken
      within 2 weeks prior to treatment, and postlaser measurements were obtained
      within 3 months after treatment. Only one eye per patient was evaluated. RESULTS:
      Mean differences between prelaser and postlaser measurements were significantly
      different from zero: (1) Contrast sensitivity, mean difference = 0.24 log units
      (P < 0.0001); (2) High glare disability using Pelli-Robson chart, mean difference
      = 0.15 log units (P = 0.004); (3) Visual acuity using ETDRS chart, mean
      difference = 11 letters (P < 0.0001); 4) High glare disability using ETDRS chart,
      mean difference = 7 letters (P = 0.005). CONCLUSIONS: Using the above methods for
      visual function testing, Nd:YAG laser capsulotomy is shown to significantly
      improve visual acuity, contrast sensitivity, and glare disability measurements as
      compared with prelaser values. The ophthalmologist may find it helpful to
      document the last two measurements prior to Nd:YAG laser capsulotomy, especially
      in patients who have good visual acuity but complain of glare sensitivity.

PMID- 9261316
TI  - Rapid diagnosis of adenoviral conjunctivitis on conjunctival swabs by 10-minute
      immunochromatography.
AB  - PURPOSE: Several methods are available for the diagnosis of acute conjunctivitis,
      all of which are time-consuming or require the use of a well-equipped laboratory.
      A new method, immunochromatography (IC), for detecting the presence of adenovirus
      (Ad) has been developed. Two direct rapid tests to detect Ad antigen, IC and
      enzyme immunoassay (EIA), were compared with regard to sensitivity, specificity,
      and technical complexity. METHODS: The study materials consisted of 130 swabs
      from patients with conjunctivitis (95 samples of adenoviral conjunctivitis proven
      by positive virus DNA on polymerase chain reaction [PCR], 35 samples of
      nonadenoviral conjunctivitis proven by PCR). IC is a one-step procedure that
      detects the presence of adenoviral antigen by sandwich EIA on a paper disc.
      RESULTS: In 95 adenoviral DNA-positive samples by PCR, the sensitivity and
      specificity of IC were 54.7% and 97.1%, respectively, whereas those of EIA were
      50.5% and 100%, respectively. By IC, PCR-positive Ad type 3 was recognized in
      31%; Ad4 in 100%; Ad7 in 60%; Ad8 in 67%; and Ad37 in 59%, showing similar
      positivity rates for different serotypes (except Ad7) to those using EIA. Visual
      determination of the presence of Ad took an average of 10 minutes by IC compared
      with 70 minutes by EIA. CONCLUSIONS: These results indicate that IC is a more
      rapid and easier test compared with EIA, and it has high specificity. Detection
      of Ad antigen by this simple and rapid method will serve physicians as a useful
      tool for early diagnosis and prevention of adenoviral conjunctivitis.

PMID- 9261317
TI  - Systemic cyclosporine A in severe atopic keratoconjunctivitis.
AB  - OBJECTIVE: Atopic keratoconjunctivitis (AKC) is a potentially blinding disease.
      It is usually associated with atopic dermatitis that has been managed
      successfully with systemic cyclosporine A (CSA) in some severe forms of the
      disease. In this study, the authors evaluated systemic CSA therapy in patients
      with severe AKC. DESIGN: Cohort Retrospective study. PARTICIPANTS: Four patients
      aged 31 to 64 with severe AKC and atopic dermatitis refractory to or dependent on
      steroid therapy. INTERVENTION: The patients received oral CSA. MAIN OUTCOME
      MEASURES: Ocular inflammation, skin condition, CSA treatment methods (dosage,
      duration), CSA-related side effects. RESULTS: Daily dosage of oral CSA was 3 to 5
      mg/kg and mean duration of treatment was 37 months (range, 22-48 months). Ocular
      inflammation was controlled totally in three patients. One patient responded only
      partially to treatment. Side effects included renal toxicity in one patient.
      Reduction of CSA dosage resulted in normalization of serum creatinine level.
      CONCLUSIONS: This report suggests that systemic CSA represents an interesting
      alternative therapy in severe AKC.

PMID- 9261318
TI  - Treatment of Nocardia asteroides keratitis with polyhexamethylene biguanide.
AB  - PURPOSE: Polyhexamethylene biguanide (PHMB) is a polymeric biguanide disinfectant
      that has been used previously in the treatment of Acanthamoeba keratitis. The
      authors report the first case of Nocardia asteroides keratitis treated
      successfully with PHMB. Further studies documenting the efficacy of PHMB against
      N. asteroides in vitro also are presented. METHODS: A soft contact lens wearer
      presented with an infectious keratitis. Cultures from the cornea grew N.
      asteroides. The infection resolved with the treatment with PHMB 0.02%. Serial
      dilutions of PHMB were performed against N. asteroides in culture. RESULTS: In
      vitro dilution studies determined that the minimal inhibitory concentration for
      PHMB against the tested isolate of N. asteroides was 0.01%. This is a
      concentration that has been shown to be well tolerated by the cornea in vivo.
      CONCLUSIONS: Polyhexamethylene biguanide is effective against both Acanthamoeba
      and Nocardia and may have a wider range of usefulness than that currently
      recognized. Further testing, both in vitro and in vivo, is required.

PMID- 9261319
TI  - Infectious posterior scleritis caused by Pseudallescheria boydii.
      Clinicopathologic findings.
AB  - PURPOSE: The purpose of the study is to describe an unusual case of infectious
      posterior scleritis after excision of a pterygium. METHODS: The case history of a
      patient in whom anterior and posterior scleritis developed after excision of a
      pterygium is reviewed. Histopathologic findings are presented. RESULTS:
      Pathologic examination results of a scleral biopsy site and the eye showed
      extensive involvement of the posterior sclera with fungi that on culture grew
      Pseudallescheria boydii. The development of posterior scleral thickening and
      intrascleral abscesses gave the clinical impression of autoimmune posterior
      scleritis or possible tumor. Ultrasonography and computed tomography scan of the
      eye and orbit proved particularly helpful in following progression of scleral
      involvement. CONCLUSIONS: Pseudallescheria boydii is capable of causing an
      infectious posterior scleritis, which can mimic autoimmune posterior scleritis.
      The use of systemic immunosuppressive agents contributed to this unusual clinical
      presentation. Progression of posterior scleritis in the face of apparent adequate
      immunosuppressive therapy always should suggest the possibility of tumor or
      infection.

PMID- 9261320
TI  - Astigmatism induced by spherical photorefractive keratectomy corrections.
AB  - PURPOSE: The purpose of the study is to evaluate the induced astigmatism after
      spherical photorefractive keratectomy on the Summit Omnimed (Summit Instruments,
      Waltham, MA) and the Nidek EC-5000 (Nidek Co. Ltd, Aichi, Japan) excimer lasers.
      METHODS: A total of 4269 eyes of 3289 patients were treated with a 5-mm optical
      zone using the Summit Omnimed excimer laser and 1825 eyes of 1303 patients
      treated with the Nidek EC-5000 excimer laser. The final astigmatic refractive
      outcome was compared with the initial refraction by vector analysis (Alpin and
      Jaffe method). RESULTS: Subjective astigmatic refraction for the Summit laser
      reduced from a mean of -0.39 diopter (D) +/- standard deviation (SD) 0.33 D
      (range, 0 to -2.50 D) to -0.33 D +/- SD 0.41 D (range, 0 to -3.00 D). Surgically
      induced astigmatism (SIA) had a mean of 0.42 +/- SD 0.34 D (range, 0 to 2.89 D).
      Mean SIA increased with increasing preoperative astigmatism by 0.60 D SIA for
      every 1.00 D of preoperative cylinder. For the Nidek laser, subjective astigmatic
      refraction changed from a mean of -0.18 D +/- SD 0.21 D (range, 0 to -1.25 D) to 
      0.30 D +/- SD 0.33 D (range, 0 to -3.00 D). Surgically induced astigmatism had a
      mean of -0.32 D +/- SD 0.29 (range, 0 to 3.05 D). Mean SIA increased with
      increasing preoperative astigmatism by 0.47 D SIA for every 1.00 D of
      preoperative cylinder. CONCLUSIONS: The authors show that spherical
      photorefractive keratectomy corrections can induce significant astigmatic change,
      particularly if a large amount of preoperative astigmatism is present.

PMID- 9261321
TI  - Results of excimer laser retreatment of residual myopia after previous
      photorefractive keratectomy.
AB  - BACKGROUND: Nine percent to 30% of all patients who undergo a single excimer
      laser photorefractive keratectomy (PRK) do not achieve an unaided visual acuity
      of 20/ 40 or better and may require optical correction to obtain adequate vision.
      METHODS: The authors performed a retrospective analysis of the records of 164
      patients who had undergone retreatment with the excimer laser for residual myopia
      after a previous PRK. Mean follow-up was 35.5 +/- 15.2 weeks (range, 26-104
      weeks). RESULTS: The mean spherical equivalent (MSE) before retreatment was -2.59
      +/- 1.36 diopter (D) (range, -0.50 to -7.75 D). The final MSE after reablation
      was -0.52 +/- 1.36 D (range, 2.50 to -5.50). Of the 164 patients, 107 (65.2%)
      obtained a final refraction within 1.00 D of emmetropia and 111 (67.3%) achieved
      an unaided visual acuity of 20/40 or better. Only 10 patients (6.1%) lost more
      than one Snellen line of best-corrected visual acuity. The final MSE result for
      the subgroup of patients who had a pre-retreatment myopia of between -0.50 and 
      1.90 D (-0.31 +/- 1.09 D) was significantly closer to emmetropia than that of the
      subgroup with a residual myopia of -4.00 to -7.75 D (-1.62 +/- 1.94 D).
      CONCLUSIONS: Excimer laser retreatment may provide a relatively safe and
      predictable method of correcting residual myopia after an earlier PRK with a 25%
      extra correction recommended for residual myopia.

PMID- 9261322
TI  - Dilute topical proparacaine for pain relief after photorefractive keratectomy.
AB  - PURPOSE: The purpose of the study is to determine whether there is a
      nonanesthetic and nontoxic concentration of topical proparacaine that can be
      applied repeatedly to the cornea to reduce pain after photorefractive keratectomy
      (PRK). METHODS: Part I: To determine a nonanesthetic concentration, the corneal
      sensitivity of 50 healthy volunteers was assessed using aesthesiometry before and
      after a drop of either 0.01%, 0.025%, 0.05%, 0.1%, or 0.2% topical proparacaine.
      Ten volunteers similarly were tested with multiple doses of 0.05% proparacaine.
      To evaluate toxicity, ten healthy volunteers self-administered 0.05% proparacaine
      to one eye and placebo to the other eye every 15 minutes for 12 hours on day 1
      and every hour for 12 hours on days 2 through 7. Subjects were assessed
      throughout the week using visual acuity, slitlamp examination, aesthesiometry,
      and ultrasonic pachometry. Part II: In a prospective, double-masked study, 34
      patients who underwent PRK (48 eyes) self-administered either topical 0.05%
      proparacaine or placebo for 1 week after PRK as needed to reduce pain. Patients
      recorded their pain score before and after drop use and answered a pain-relief
      questionnaire. RESULTS: Part I: Proparacaine concentrations greater than or equal
      to 0.1% eliminated sensation from some corneas; concentrations of less than or
      equal to 0.05% were never fully anesthetic. No corneal toxicity was observed
      except for some minimal punctate staining in both treatment and placebo eyes.
      Part II: Patients in the treatment group had significantly more pain relief (P <
      0.001) for a longer period (P < 0.001) than did patients in the control group.
      Average change in pain score was significantly greater in the treatment group (P
      < 0.002). No significant difference in the number of days needed to reach
      complete epithelial healing was found between the two groups (P < 0.18).
      CONCLUSIONS: Dilute (0.05%) topical proparacaine is nonanesthetic and nontoxic,
      and can be used safely for at least 1 week to reduce pain after PRK.

PMID- 9261323
TI  - Corneal topography of excimer laser photorefractive keratectomy using a 6-mm beam
      diameter. Summit PRK Topography Study Group.
AB  - OBJECTIVE: The purpose of the study is to define qualitative patterns of corneal
      topography after excimer laser photorefractive keratectomy (PRK) using a 6-mm
      beam diameter, investigate changes in patterns over time, and identify
      associations of topography patterns with clinical outcomes. DESIGN: Multicenter,
      prospective cohort study. PARTICIPANTS: Ninety-eight eyes of 90 patients with
      myopia who had undergone PRK using the Summit Technology, Inc., excimer laser
      with a 6-mm beam diameter. INTERVENTION: Computer-assisted videokeratography data
      were analyzed for eyes having undergone PRK. Topography patterns at 3, 6, and 12
      months after surgery were classified and associations with clinical outcomes
      assessed. MAIN OUTCOMES MEASURED: Topography patterns after PRK were determined
      at 3, 6, and 12 months after surgery. Associations with preoperative
      characteristics of age and attempted correction, and postoperative outcomes of
      uncorrected and spectacle-corrected visual acuity, predictability, astigmatism,
      corneal haze, glare, halo, and patient satisfaction were analyzed. RESULTS: At 1
      year, 21.4% of corneas showed a homogeneous topography, 27.6% showed a toric-with
      axis configuration, 10.2% showed a toric-against-axis configuration, 7.1% showed
      an irregularly irregular topography, 24.5% showed a keyhole/semicircular pattern,
      and 9.2% showed focal topographic variants. From 3 to 6 months, 40.1% of maps
      changed; from 6 to 12 months, 53.1% of maps changed, generally to optically
      smoother, regular patterns. Older age and higher attempted correction were
      associated with the development of more irregular patterns. The irregular groups
      showed worse predictability than did the regular groups and a tendency for slight
      overcorrection. The average reported glare/halo of 1.33 (scale = 0 to 5) in this
      study was less than in a previous study of the 4.5- to 5-mm treatment zone.
      However, of six patients expressing dissatisfaction with the results of surgery,
      three ranked their glare or halo at the maximum level. CONCLUSIONS: Topography
      patterns using a 6-mm beam diameter are identifiable, improve with time, and may
      affect clinical outcomes after photorefractive keratectomy (PRK). The
      keyhole/semicircular pattern is more prevalent with a 6 mm treatment zone than
      with smaller treatment zones. Although optical side effects of glare and halo
      appear to be reduced with the 6-mm treatment, a small number of patients still
      report substantial glare or halo after the procedure.

PMID- 9261324
TI  - Lensification of the posterior corneal surface. An unusual proliferation of lens
      epithelial cells.
AB  - BACKGROUND: Abnormal proliferation of lens epithelial cells occurs in a variety
      of situations, such as anterior and posterior subcapsular cataracts and secondary
      cataract formation. The purpose of this report is to document an unusual
      occurrence of diffuse proliferation of lens epithelium and capsule along the
      posterior corneal surface. METHODS: The authors performed penetrating
      keratoplasty to remove an edematous and scarred cornea is a 19-year-old Indian
      man. Three years previously, the patient had undergone penetrating keratoplasty
      and extracapsular cataract extraction to treat a nonhealing corneal ulcer. The
      keratectomy specimen was processed for conventional light microscopy. Five
      micrometer sections were stained with hematoxylin-eosin and the periodic acid
      Schiff methods. RESULTS: Intraoperatively, the eye was found to be aphakic with
      an intact posterior capsule. The iris tissue consisted of fibrotic, pigmented
      remnants adherent to the peripheral cornea for 360 degrees, closing the angle and
      capsular fornix. Histologically, cataractous lens material including proliferated
      lens epithelial cells and capsule diffusely lined the posterior corneal surface
      along a thick retrocorneal fibrous membrane. CONCLUSIONS: This case represents a
      new category of lens epithelial cell proliferation or migration or both that
      covers entirely the posterior corneal surface. The authors believe the term
      lensification is appropriate for the condition described herein.

PMID- 9261325
TI  - Etiology and prognosis of acute, late-onset esotropia.
AB  - OBJECTIVE: The purpose of the study is to review etiologies and outcomes of
      sudden, late-onset esotropia. DESIGN: The authors reviewed charts of patients in
      whom acute, comitant, constant esotropia developed after 5 years of age. MAIN
      OUTCOME MEASURES: The authors evaluated final ocular alignment, treatment,
      fusion, apparent etiologies, and associated neurologic conditions. RESULTS: Ten
      patients met entry criteria with documentation of previous orthotropia. Ages
      ranged from 5 to 35 years. Esotropia at near ranged from 16 to 70 prism diopters.
      In seven patients, the esotropia improved partially or completely with correction
      of hypermetropia. Eight patients required surgery. In only one patient were
      neuroimaging studies positive, associated ophthalmic and systemic findings
      identified, and underlying neurologic disease diagnosed. CONCLUSIONS: Sudden,
      late-onset esotropia may be caused by an uncorrected refractive error. If no
      other neurologic signs are present, underlying intracranial disease is unlikely.

PMID- 9261326
TI  - A study of topical nonsteroidal anti-inflammatory drops and no pressure patching
      in the treatment of corneal abrasions. Corneal Abrasion Patching Study Group.
AB  - OBJECTIVE: To evaluate the effectiveness of an ophthalmic nonsteroidal anti
      inflammatory drug (NSAID) in the treatment of noninfected, non-contact lens
      related, traumatic corneal abrasions and no pressure patch. DESIGN: A single
      center, randomized, double-masked, placebo-controlled study. PARTICIPANTS: One
      hundred patients with noninfected, non-contact lens-related, traumatic or foreign
      body removal-related corneal abrasions less than 36 hours in duration.
      INTERVENTION: All patients received a cycloplegic drop and erythromycin or
      polymyxin B (Polysporin Ophthalmic Ointment, Burroughs Wellcome, Research
      Triangle Park, NC). Patients were then randomized to receive either ketorolac
      tromethamine 0.5% ophthalmic solution or control vehicle drops. MAIN OUTCOME
      MEASURES: The main outcome measures were six subjective symptoms monitored daily,
      evaluation of corneal abrasion, and determination of adverse events. Long-term
      complications were determined 3 to 8 months after randomization. RESULTS: Twelve
      patients were excluded from the study. One day after randomization, patients
      receiving ketorolac tromethamine 0.5% ophthalmic solution noted significantly
      decreased levels of pain (P < 0.002), photophobia (P < 0.009), and foreign body
      sensation (P < 0.003) as compared with the control vehicle group. In addition,
      the time to resumption of normal activities was shorter in the group who received
      ketorolac tromethamine 0.5% ophthalmic solution (P < 0.001). There was no
      statistical difference in the amount of tearing, healing time, acuity changes, or
      complication rates between the two groups. CONCLUSIONS: Ketorolac tromethamine
      0.5% ophthalmic solution provides increased patient comfort without clinical
      adverse effects when used as adjunctive therapy in the treatment of noninfected,
      non-contact lens-related, traumatic corneal abrasions.

PMID- 9261327
TI  - Corneal endothelial photography. Three-year revision. American Academy of
      Ophthalmology.
AB  - When properly done, corneal endothelial photography has been shown to be a
      relatively safe, reliable, and effective means to ascertain corneal endothelial
      cell density (cells/ mm2) and to provide information about endothelial cell
      morphometry. Currently, this procedure is not essential prior to routine cataract
      surgery, but may be indicated in situations in which the cornea is suspected of
      having endothelial abnormality and in which the accuracy of the estimated cell
      count from slit-lamp biomicroscopy is thought to be less than satisfactory. These
      situations include but are not limited to (1) eyes before secondary lens
      implantation; (2) eyes in which the status of the corneal endothelium is of
      concern because of a history of trauma, acute glaucoma, inflammation, or corneal
      transplantation; (3) eyes that contain intraocular lenses that are partially
      dislocated or are suspected of causing chronic inflammation or endothelial
      injury; and (4) eyes in which the fellow eye has a history of unexplained corneal
      edema.

PMID- 9261329
TI  - The CD28-B7 costimulatory pathway and its role in autoimmune disease.
AB  - The activation of naive CD4+ T cells requires two discrete signals: a signal
      delivered by the T cell receptor following recognition of antigen and an
      accessory signal transduced when costimulatory receptors interact with their
      ligands. Particularly important in the development of an immune response to
      foreign antigens is the T cell molecule CD28, which delivers a potent costimulus
      when engaged by ligands, B7-1 and B7-2, on antigen-presenting cells. It is
      interesting that blockade of B7 molecules, which disrupts interactions with CD28
      and prevents delivery of the CD28 costimulus, also alters the immune responses to
      self antigens and prevents the development of clinical disease in murine models
      of systemic and organ-specific autoimmunity. Herein we review the roles of CD28
      and its B7 ligands in the pathogenesis of autoimmunity, discuss efforts to treat
      animal models of autoimmunity by modifying the CD28 signal, and consider the
      mechanisms by which manipulation of the CD28 signal alters the course of
      experimental autoimmune disease.

PMID- 9261328
TI  - CSF-1 signal transduction.
AB  - Colony-stimulating factor-1 (CSF-1) or macrophage-CSF (M-CSF) is a growth factor
      involved in the proliferation, differentiation, and activation of cells of the
      monocyte/macrophage lineage. Its receptor is the homodimeric, tyrosine kinase
      product of the c-fms proto-oncogene, which contains a so-called kinase insert
      domain. This review focuses mainly on recent studies of signal transduction
      events that are initiated on interaction of CSF-1 and its receptor. A summary is
      given of the tyrosine autophosphorylation sites on c-Fms identified to date,
      including their interaction with various substrates and their possible
      significance for signal transduction and cellular function. In addition, the
      signal transduction pathways that have been identified to lie downstream of
      activated c-Fms are reviewed. Although it is apparent that there have been many
      recent significant developments in our understanding of CSF-1 signaling, a number
      of examples are mentioned of significant discrepancies in the literature, some
      possible reasons for which can sometimes be offered. It is also apparent that any
      particular biochemical response or signal transduction pathway, even though
      widespread in other ligand receptor/cellular systems, including those with
      similar receptor structures to c-Fms, may not be relevant to CSF-1 signaling. The
      relevance of any potentially important molecular signaling pathway activated by
      CSF-1 in cells in vitro will ultimately have to be related to the functions of
      monocytes/macrophages in vivo.

PMID- 9261330
TI  - Leukocyte contribution to parenchymal cell death in an experimental model of
      inflammation.
AB  - The relationship between leukocyte migration and parenchymal cell death in vivo
      remains poorly documented. Accordingly, cell killing in the rat mesentery, as
      recorded by propidium iodide staining, was investigated with an intravital
      approach. Superfusion of platelet-activating factor (PAF, 10(-8) M) or N-formyl
      methionyl-leucyl-phenylalanine (fMLP, 10(-8) M) led to extensive leukocyte
      extravasation but no significant cell death. In contrast, pretreatment with 10(
      8) M PAF or fMLP for 1 h, followed by superfusion of PAF in combination with fMLP
      (both at 10(-8) M) led to an increase in cell death. Mesenteric parenchymal cells
      but no endothelial cells were killed. Some of the dead cells were identified as
      granulocytes/monocytes that were already in the tissue at the start of the
      experiment. The incidence of cell death was lower but not eliminated when
      leukocyte migration was blocked with a monoclonal antibody against CD18. A
      xanthine oxidase inhibitor, BOF-4272, failed to diminish cell death, whereas a
      hydroxyl radical scavenger, dimethylthiourea, attenuated cell killing without an
      effect on the number of adhering and migrating leukocytes. These observations
      demonstrate that leukocytes serve as a factor in the killing of extravascular
      cells only after the development of a level of stimulation that differs from that
      required to induce a migratory stimulus into the extravascular space.

PMID- 9261331
TI  - Porcine bone marrow myeloid cells: phenotype and adhesion molecule expression.
AB  - The purpose of this study was the discrimination of porcine bone marrow
      hematopoietic cell (BMHC) subpopulations and cell maturation stages by using
      cluster of differentiation (CD) and Swine Workshop Cluster (SWC) molecules,
      combined with cell size, granularity, and the capacity to generate an oxidative
      burst. SWC3 was the earliest myeloid marker identified in the differentiation
      pathways. Through SWC3/SWC8 double labeling, three populations committed to the
      myeloid lineage were discriminated: early myeloid progenitors, which were
      SWC3lowSWC8-; cells committed to the granulocytic lineage, which were SWC3+SWC8+;
      monocytic cells, which were SWC3+(-)SWC8-. The SWC3lowSWC8- myeloid progenitors
      expressed high levels of CD44 and CD49d, but no CD14. Among the SWC3+SWC8+
      granulocytic cells, the most immature were CD14-CD11a/18-CD44low, an intermediate
      stage was CD14+CD11a/18lowCD44-, and the most mature were CD14+CD11a/18high
      CD44high. Only the latter could generate a rapid oxidative burst. Moreover,
      during granulocytic maturation, a constant decrease in CD49d/29 expression was
      observed. In contrast, the SWC3+SWC8- monocytic cells were mainly CD14+ and
      expressed high levels of the adhesion molecules. These results define porcine
      hematopoietic differentiation and maturation stages. Similarities in human and
      porcine adhesion molecule expression have been identified, suggesting common
      functionalities in the regulation of hematopoiesis and the potential of the pig
      as a model for hematopoietic studies.

PMID- 9261332
TI  - Activation-associated changes in blood and bone marrow neutrophils.
AB  - Accelerated granulocytopoiesis and polymorphonuclear leukocyte (PMN) activation
      via the complement system are important events in the inflammatory response. This
      study tests the hypothesis that PMN of the peripheral blood and the bone marrow
      behave differently when stimulated with zymosan-activated plasma (ZAP). PMN were
      treated with ZAP and processed to determine the content and distribution of F
      actin, the expression of CD18-integrins, and the cell area/shape with the use of
      a combination of flow cytometry, fluorescence, and light microscopy. The results
      show that untreated bone marrow PMN display similar F-actin content and cell area
      but express less CD18 than peripheral blood PMN. ZAP-activated peripheral blood
      PMN show a marked increase in the F-actin content, CD18 expression, cell area,
      and length. Highly elongated PMN develop a polar shape in which microfilaments
      are redistributed in cell protrusions and CD18 is located in the uropod and the
      lamellipodium. In comparison, activated bone marrow PMN show a lower and more
      transient increase in the F-actin content, express less CD18, show a reduced
      increase in the cell area, and display reduced polarity and microfilament
      redistribution. We conclude that bone marrow PMN show lower complement-activation
      response than peripheral blood PMN and suggest that the lower expression of
      surface membrane integrins and related cytoskeletal filaments may account for
      their reduced ability to develop the polar shape required for diapedesis and
      migration.

PMID- 9261333
TI  - Coupling of neutrophil apoptosis to recognition by macrophages: coordinated
      acceleration by protein synthesis inhibitors.
AB  - Onset of apoptosis in many cell types, including the neutrophil granulocyte,
      leads to recognition and ingestion by macrophages, a key regulatory step in
      clearance of inflammatory cells from inflamed sites. These studies examined the
      requirement for protein synthesis in neutrophil apoptosis and in the recognition
      of apoptotic neutrophils by monocyte-derived macrophages. Treatment with
      cycloheximide or actinomycin D produced a time- and concentration-dependent
      acceleration of apoptosis in populations of neutrophils purified from human
      peripheral blood. Both compounds caused significant promotion of apoptosis after
      8 h (apoptosis was 7.7 +/- 2.9%, mean +/- SEM, in control populations, 57.5 +/-
      4.9% in cycloheximide-treated, and 73.4 +/- 5.5% in actinomycin D-treated
      populations, n = 4, P < 0.001), which was associated with loss of neutrophil
      functional ability (assessed by shape change on N-formyl-methionyl-leucyl
      phenylalanine stimulation) and increased macrophage recognition and ingestion of
      neutrophil populations with accelerated apoptosis. These results support the
      existence of survival proteins, which act as intracellular suppressors of
      programmed cell death. However, protein synthesis was not required for the
      recognition process because macrophage recognition was increased pari passu with
      the morphology of apoptosis.

PMID- 9261334
TI  - Leukotriene B4-activated human endothelial cells promote transendothelial
      neutrophil migration.
AB  - We explored the effect of leukotriene B4 (LTB4) on endothelial cells in LTB4
      induced transendothelial migration (TEM) of neutrophils as an in vitro model of
      neutrophil extravasation. Chemotactic response of human neutrophils to LTB4 was
      significantly lower than that in response to N-formyl-methionyl-leucyl
      phenylalanine (fMLP), whereas the extent of TEM in response to LTB4 was
      significantly higher than that to fMLP. The study on random migration induced by
      LTB4 and fMLP also showed similar results, which indicated that LTB4 might affect
      the human umbilical cord vein endothelial cell (HUVEC) barrier. Neutrophil TEM
      was induced by pretreatment of HUVEC monolayer with LTB4 but not with fMLP.
      Treatment of endothelial cells by ONO-4057, a LTB4 receptor antagonist, abolished
      the effect of LTB4 almost completely whereas neutrophils treated with ONO-4057
      could transmigrate through HUVEC treated with LTB4. These findings indicated that
      LTB4 could induce neutrophil TEM by acting on HUVEC.

PMID- 9261335
TI  - Mast cell granules potentiate endotoxin-induced interleukin-6 production by
      endothelial cells.
AB  - Mast cells are constituent cells of vascular tissue and their numbers are
      increased in atherosclerotic vessels. To gain insight into the role of mast cells
      in vascular inflammation, the effect of mast cell granules (MCG) on endothelial
      cell production of interleukin-6 (IL-6) was examined. Human umbilical vein
      endothelial cells (HUVEC) were cultured with lipopolysaccharide (LPS) in the
      presence or absence of rat peritoneal MCG and IL-6 production was assayed by
      enzyme-linked immunosorbent assay. The interaction of MCG with HUVEC in culture
      was examined by electron microscopy (EM). The EM studies revealed that MCG are
      internalized by HUVEC and appear intact even after 24 h in culture. Unactivated
      HUVEC produced little or no IL-6 either in the presence or absence of MCG.
      Treatment of HUVEC with LPS stimulated IL-6 production in a dose- and time
      dependent fashion. Addition of MCG to LPS-activated HUVEC-resulted in the
      potentiation of IL-6 production at all LPS doses. MCG-induced enhancement of IL-6
      production was evident even at a mast cell-to-endothelial cell ratio of 1:32. The
      enhancement of IL-6 production by MCG was also seen when tumor necrosis factor
      alpha was used as an activator. Although potentiation was evident when MCG were
      added 6 h before or after LPS stimulation, the maximum effect was noted when MCG
      and LPS were added simultaneously. MCG-mediated enhancement of IL-6 production
      was abrogated by pretreating MCG with protease inhibitors. Although MCG proteases
      potentiate IL-6 production by HUVEC, they do not degrade secreted IL-6. These
      results demonstrate that MCG interact with endothelial cells and modulate the
      production of an important inflammatory cytokine.

PMID- 9261336
TI  - Effect of neutrophil serine proteinases and defensins on lung epithelial cells:
      modulation of cytotoxicity and IL-8 production.
AB  - Neutrophil accumulation in the lung may contribute to tissue injury as observed
      in inflammatory diseases. Both oxidative and non-oxidative mechanisms are
      involved in neutrophil-mediated tissue injury. Non-oxidative mechanisms include
      the release of neutrophil granule proteins such as the serine proteinases
      elastase and cathepsin G, and the non-enzymatic defensins. Because stimulated
      neutrophils are thought to release their products simultaneously, we investigated
      possible interactions between purified defensins and serine proteinases with
      respect to induction of cellular injury and their ability to induce interleukin-8
      (IL-8) synthesis in cells of the lung epithelial cell line A549. Whereas
      defensins induced cell lysis, elastase and cathepsin G induced detachment of A549
      cells. Co-incubation of elastase and cathepsin G revealed an additive effect on
      detachment, whereas defensins inhibited serine proteinase-induced detachment.
      Vice versa, both serine proteinases reduced defensin-induced cell lysis.
      Furthermore, elastase and cathepsin G prevented defensin-induced IL-8 synthesis.
      In contrast, no inhibitory interaction between cathepsin G and defensins was
      observed with respect to their antibacterial activity. The results from this
      study indicate that, at sites of inflammation, neutrophil-mediated injury might
      be regulated by interactions between released defensins and serine proteinases.

PMID- 9261337
TI  - Human monocyte ATP-induced IL-1 beta posttranslational processing is a dynamic
      process dependent on in vitro growth conditions.
AB  - Despite a large production capacity, freshly isolated lipopolysaccharide (LPS)
      activated human monocytes release only a small percentage of their newly
      synthesized interleukin (IL)-1 beta into the medium. Extracellular ATP, acting
      via surface P2z-type purino-receptors, increases cytokine posttranslational
      processing. To explore whether this ATP response was affected by culture
      conditions, monocytes were maintained for different time periods in the absence
      and presence of various media components including fetal bovine and human sera
      and recombinant human cytokines. The ability of monocytes to produce radiolabeled
      pro-IL-1 beta in response to LPS and to posttranslationally process the
      procytokine after ATP stimulation was affected both by time in culture and by the
      presence of specific media components. These observations indicate that ATP's
      ability to promote human monocyte IL-1 beta posttranslational processing is a
      dynamic process that is subject to regulation by cytokines and/or growth factors.
      Changes in monocyte/macrophage ATP responsiveness may provide an important
      regulatory mechanism for the control of IL-1 biological activity in vivo.

PMID- 9261338
TI  - 5-Lipoxygenase inhibitors potentiate effects of TGF-beta 1 on the differentiation
      of human leukemia HL-60 cells.
AB  - It was clearly demonstrated that two structurally different inhibitors of 5
      lipoxygenase (5-LPO) metabolism (leukotriene synthesis), i.e. MK-886 and
      esculetin, when combined with transforming growth factor-beta 1 (TGF-beta 1),
      significantly enhanced the differentiation but did not change proliferation (i.e.
      cell number and cell cycle parameters) of human leukemia HL-60 cells in vitro.
      Although cell morphology and measurement of cell surface antigens (CD11b, CD14,
      and CD66b) after 48 h of combined treatment with MK-886 and TGF-beta 1 suggested
      a shift of the HL-60 cell population into more differentiated stages of
      myelopoiesis, cells with a fully mature phenotype were not observed. The effects
      on differentiation were better distinguished in the functional parameters of
      differentiation, i.e. oxidative burst of cells as detected by chemiluminescence
      and the nitroblue tetrazolium reduction test. Detailed statistical analysis of
      these data proved a significant synergistic interaction between TGF-beta 1 and
      inhibitors of 5-LPO metabolism. The differentiation effects of TGF-beta 1 alone
      and especially of its combination with MK-886 were most pronounced when the cells
      were pretreated with dimethyl sulfoxide or all-trans-retinoic acid. The results
      imply that either the lack of 5-LPO metabolites or a certain type of mis-balance
      in arachidonic acid metabolism can modulate the TGF-beta 1 effect on myeloid
      differentiation.

PMID- 9261339
TI  - Differential regulation of biosynthesis of cell surface and secreted TNF-alpha in
      LPS-stimulated murine macrophages.
AB  - Activated macrophages synthesize a 26-kDa cell surface form and a 17-kDa secreted
      form of tumor necrosis factor alpha (TNF-alpha). This study was designed to
      investigate possible differences between the biosynthesis of these two forms by
      murine peritoneal exudate cells (PEC) and a murine macrophage cell line (RAW
      264.7) stimulated with lipopolysaccharide (LPS). Both PEC and RAW 264.7 cells
      produced surface and secreted TNF-alpha in response to LPS in a dose-dependent
      manner. However, much lower concentrations of LPS (100 ng/mL) were needed for
      optimal expression of surface TNF-alpha than for secreted TNF-alpha (1
      microgram/mL). Furthermore, concentrations of actinomycin D that inhibit the
      synthesis of new mRNA and the production of secreted TNF-alpha did not block the
      expression of surface TNF-alpha on LPS-stimulated cells. Cycloheximide inhibited
      the production of both forms of TNF-alpha at similar concentrations. The effects,
      on the expression of the surface form of TNF-alpha, of various pharmacological
      agents known to inhibit the production of secreted TNF-alpha were studied. It was
      found that: (1) dexamethasone, a glucocorticoid agonist and (2) ETI and ETYA,
      inhibitors of lipoxygenase, had no effect on cell surface TNF-alpha at
      concentrations that inhibited secreted TNF-alpha. The data show that there are
      differences in the production of surface and secreted TNF-alpha and indicate that
      the regulation of synthesis of this protein is more complex than that suggested
      by a mere precursor/product relationship between the two forms.

PMID- 9261340
TI  - Contrasting effects of alpha- and beta-androstenediol on oncogenic myeloid cell
      lines in vitro.
AB  - The in vitro effects of 17 alpha AED, the isomer of 5-androstene-3 beta,17 beta
      diol (17 beta AED) on the basal growth of murine RAW 264.7, P388D1, and human HL
      60 cells were investigated. 17 alpha AED treatment of RAW cells for 48 h reduced
      total cell number without increasing cell death as detected by trypan blue
      exclusion. At these doses, DNA synthesis as measured by [3H]thymidine
      incorporation was suppressed by as much as 65%, P < 0.05. This effect was time-
      and dose-dependent and reversible on removal of the steroid. Similar results were
      obtained with P388D1 and human HL-60 cell lines. At 50 nM or above, 17 alpha AED
      induced apoptosis in RAW cells and HL-60 as detected by transmission electron
      microscopy and TUNEL assays. By contrast, treating cells with the isomer 17 beta
      AED had no such effect. These data suggest that the balance between the anti
      proliferative effect of 17 alpha AED and the proliferative effects of 17 beta AED
      may determine the overall level of myelopoiesis.

PMID- 9261341
TI  - Endogenous PMN-derived reactive oxygen intermediates provide feedback regulation
      on respiratory burst signal transduction.
AB  - The role of polymorphonuclear leukocytes (PMN) in stemming systemic infection is
      executed mainly by the utilization of molecular O2 leading to the production of
      reactive oxygen intermediates (ROI). PMN-derived ROI also serve as intra- and
      extracellular second messengers providing both positive and negative feedback on
      cellular autoregulation. We investigated the effect of endogenous ROI on two
      signal transducing pathways: the receptor (R)-G-protein-phospholipase D (PLD) and
      receptor (R)-G-protein-phospholipase C pathways responsible for the subsequent
      interleukin-8 (IL-8)-induced PMN respiratory burst. Purified human PMN were
      primed with LPS adhered to plastic surfaces and stimulated with IL-8 with or
      without the presence of each of five different selective ROI
      scavengers/antioxidants: DMSO, N(a)N3, L-alanine, catalase, or superoxide
      dismutase. Total IL-8 surface receptor expression was assessed by 125I-IL-8 and
      125I-labeled mAbs against IL-8R type A and B binding assays; PLD activation was
      assessed by measuring formation of phosphatidyl ethanol (PEt) in the presence of
      ethanol; PLC activation was measured by quantitative conversion of [32P]ATP
      labeled phosphatidic acid (PA) into diacylglycerol (DAG); expression of G alpha
      inhibitory subunit was assessed by SDS-PAGE and immunoblotting with polyclonal
      Abs against this subunit. Production of O2-, H2O2, HClO, and myeloperoxidase
      (MPO) in the experimental model was confirmed in a separate set of experiments.
      The overall impact of antioxidants on each component of the transducing
      tripartite complex was stimulatory; however, N(a)N3 and SOD exhibited the most
      ubiquitous effect with consistent up-regulation by N(a)N3 of IL-8R expression,
      whereas even trace amounts of externally added authentic MPO significantly down
      regulated the functional activity of both effector enzymes. These results
      demonstrate a multiple site-specific targeting of the signal-transducing complex
      by endogenous PMN-derived ROI and an overall protective effect of ROI
      scavengers/antioxidants.

PMID- 9261342
TI  - Cell-specific and inducible Nramp1 gene expression in mouse macrophages in vitro
      and in vivo.
AB  - Mutations in the Nramp1 gene abolish natural resistance to infections with many
      unrelated intracellular parasites in vivo. Global cDNA amplification was used to
      analyse Nramp1 mRNA expression in bone marrow-derived cell colonies corresponding
      to either undifferentiated progenitors or to mature lymphoid, erythroid, and
      myeloid lineages. Nramp1 mRNA was detected in mature myeloid colonies expressing
      molecular markers for either the monocyte/macrophage or granulocytic lineages.
      Having established constitutive expression of Nramp1 in phagocytic cells, the
      parameters of inducible Nramp1 expression by cytokines and lipopolysaccharide
      (LPS) were studied in the mouse macrophage cell line RAW 264.7. LPS caused up
      regulation of Nramp1 expression in a time- and dose-dependent fashion. This
      induction required de novo protein synthesis and was abrogated by treatment with
      cycloheximide. Treatment with interferon-gamma (IFN-gamma) also caused a modest
      but reproducible twofold induction of Nramp1 mRNA expression. In addition,
      maximum Nramp1 mRNA induction in RAW 264.7 cells was observed after pretreatment
      with IFN-gamma followed by LPS exposure. In vivo, Nramp1 mRNA expression could be
      up-regulated in macrophage populations by intraperitoneal injection of either LPS
      or thioglycollate. Together these results indicate that Nramp1 is expressed in
      professional phagocytes of the myeloid lineage and can be further up-regulated
      during macrophage activation in response to infectious, inflammatory, or cytokine
      stimuli. Finally, the patterns of constitutive and inducible expression of Nramp1
      have been compared to those of the inducible nitric oxide synthase (iNOS) gene in
      the same cells.

PMID- 9261343
TI  - Expression status of Tax protein in human T-cell leukemia virus type 1
      transformed MT4 cells: recall of MT4 cells distributed by the NIH AIDS Research
      and Reference Reagent Program.

PMID- 9261344
TI  - Transformation and tumorigenic properties of a mutant polyomavirus containing a
      middle T antigen defective in Shc binding.
AB  - Polyomavirus middle T antigen is phosphorylated on several tyrosine residues
      which act as binding sites for cellular proteins, including phosphatidylinositol
      3-kinase, Shc, and phospholipase C-gamma. In this report we describe the
      transforming properties and tumor-inducing ability of a polyomavirus that
      contains a single-site mutation in middle T antigen which changes a tyrosine
      residue at amino acid position 250 to serine. This mutation disrupts the
      association of middle T with the transforming protein Shc. The mutant virus is
      weakly transforming, inducing foci which are smaller and of different morphology
      than those of the wild type. Although the virus induced tumors in close to 100%
      of inoculated mice, the spectrum of tumors and their morphology were altered
      compared to those of wild-type virus. The mutant virus induced a reduced
      frequency of kidney and thymic tumors. Both the mammary gland and the thymic
      tumors that were induced were histologically distinct from those induced by wild
      type polyomavirus. These results demonstrate that the signal transduction pathway
      that is deregulated by the middle T-Shc association is important for full
      transformation of cells in culture and for tumor induction in some target tissues
      in the mouse-polyomavirus system.

PMID- 9261345
TI  - Detection of an interaction between the HN and F proteins in Newcastle disease
      virus-infected cells.
AB  - For many paramyxoviruses, including Newcastle disease virus (NDV), syncytium
      formation requires the expression of both surface glycoproteins (HN and F) in the
      same cell, and evidence suggests that fusion involves a specific interaction
      between the HN and F proteins. Because a potential interaction in paramyxovirus
      infected cells has never been demonstrated, such as interaction was explored by
      using coimmunoprecipitation and cross-linking. Both HN and F proteins could be
      precipitated with heterologous antisera after a 5-min radioactive pulse as well
      as after a 2-h chase in nonradioactive medium, but at low levels. Chemical cross
      linking increased detection of complexes containing HN and F proteins at the cell
      surface. After cross-linking, intermediate- as well as high-molecular-weight
      species containing both proteins were precipitated with monospecific antisera.
      Precipitation of proteins with anti-HN after cross-linking resulted in the
      detection of complexes which electrophresed in the stacker region of the gel,
      from 160 to 300 kDa, at 150 kDa, and at 74 kDa. Precipitates obtained with anti-F
      after cross-linking contained species which migrated in the stacker region of the
      gel, between 160 and 300 kDa, at 120 kDa, and at 66 kDa. The three to four
      discrete complexes ranging in size from 160 to 300 kDa contained both HN and F
      proteins when precipitated with either HN or F antisera. That cross-linking of
      complexes containing both HN and F proteins was not simply a function of
      overexpression of viral glycoproteins at the cell surface was addressed by
      demonstrating cross-linking at early time points postinfection, when levels of
      viral surface glycoproteins are low. Use of cells infected with an avirulent
      strain of NDV showed that chemically cross-linked HN and F proteins were
      precipitated independent of cleavage of F0. Furthermore, under conditions that
      maximized HN protein binding to its receptor, there was no change in the
      percentages of HN and F0 proteins precipitated with heterologous antisera, but a
      decrease in F1 protein precipitated was observed upon attachment. These data
      argue that the HN and F proteins interact in the rough endoplasmic reticulum.
      Upon attachment of the HN protein to its receptor, the HN protein undergoes a
      conformational change which causes a conformational change in the associated F
      protein, releasing the hydrophobic fusion peptide into the target membrane and
      initiating fusion.

PMID- 9261347
TI  - Two distinct CCR5 domains can mediate coreceptor usage by human immunodeficiency
      virus type 1.
AB  - The chemokine receptor CCR5 is the major fusion coreceptor for macrophage-tropic
      strains of human immunodeficiency virus type 1 (HIV-1). To define the structures
      of CCR5 that can support envelope (Env)-mediated membrane fusion, we analyzed the
      activity of homologs, chimeras, and mutants of human CCR5 in a sensitive gene
      reporter cell-cell fusion assay. Simian, but not murine, homologs of CCR5 were
      fully active as HIV-1 fusion coreceptors. Chimeras between CCR5 and divergent
      chemokine receptors demonstrated the existence of two distinct regions of CCR5
      that could be utilized for Env-mediated fusion, the amino-terminal domain and the
      extracellular loops. Dual-tropic Env proteins were particularly sensitive to
      alterations in the CCR5 amino-terminal domain, suggesting that this domain may
      play a pivotal role in the evolution of coreceptor usage in vivo. We identified
      individual residues in both functional regions, Asp-11, Lys-197, and Asp-276,
      that contribute to coreceptor function. Deletion of a highly conserved
      cytoplasmic motif rendered CCR5 incapable of signaling but did not abrogate its
      ability to function as a coreceptor, implying the independence of fusion and G
      protein-mediated chemokine receptor signaling. Finally, we developed a novel
      monoclonal antibody to CCR5 to assist in future studies of CCR5 expression.

PMID- 9261348
TI  - Nucleotide substitutions within U5 are critical for efficient reverse
      transcription of human immunodeficiency virus type 1 with a primer binding site
      complementary to tRNA(His).
AB  - Sequence analysis of integrated proviruses of human immunodeficiency virus type 1
      (HIV-1) which utilize tRNA(His) to initiate reverse transcription [virus derived
      from pHXB2(His-AC-TGT)] revealed five additional nucleotide substitutions in the
      U5 and primer binding site (PBS) regions (ATGAC for CCTGT at nucleotides 152,
      160, 174, 181, and 200, respectively) (Z. Zhang et al., Virology 226:306-317,
      1996). We constructed a mutant proviral genome [pHXB2(His-AC-GAC)] which
      contained the ATGAC substitutions to test if they represented a necessary
      adaptation by the virus for use of tRNA(His) to initiate reverse transcription.
      Viruses from pHXB2(His-AC-TGT) and pHXB2(His-AC-GAC) were infectious. Sequence
      analysis of the U5 and PBS regions of integrated provirus from a cell culture
      infected with virus derived from pHXB2(His-AC-TGT) revealed a G-to-A change in
      CCTGT at nucleotide 181 after limited in vitro culture, suggesting that this
      nucleotide change represented an adaptation by the virus to efficiently utilize
      tRNA(His) to initiate reverse transcription. To further address this possibility,
      we used a specific mutation in reverse transcriptase (RT), a methionine-to-valine
      change in the highly conserved YMDD amino acid motif of HIV-1 RT (M184V), which
      has been shown in previous studies to influence the fidelity and activity of the
      enzyme. The M184V RT mutation was cloned into pHXB2(His-AC-GAC) and pHXB2(His-AC
      TGT). Virus derived from pHXB2(His-AC-GAC) with M184V RT had slightly delayed
      replication compared to the virus from pHXB2(His-AC-GAC) with wild-type RT; in
      contrast, virus from pHXB2(His-AC-TGT) with M184V RT was severely compromised in
      replication. Using an endogenous reverse transcription-PCR assay to analyze the
      reverse transcription of viruses obtained after transfection, we found that
      viruses derived from pHXB2(His-AC-GAC) with the wildtype RT were slightly faster
      in the initiation of reverse transcription than viruses with M184V RT. The
      initiation of reverse transcription was delayed in viruses derived from pHXB2(His
      AC-TGT) with wild-type RT and M184V RT compared to viruses derived from pHXB2(His
      AC-GAC). Finally, sequence analysis of U5 and PBS regions of proviruses from
      pHXB2(His-AC-GAC) with wild-type RT revealed considerably more nucleotide
      substitutions than in viruses derived from pHXB2(His-AC-GAC) containing the M184V
      mutation in RT after extended in vitro culture. Our studies point to a role for
      these additional nucleotide substitutions in U5 as an adaptation by the virus to
      utilize an alternative tRNA to initiate reverse transcription.

PMID- 9261346
TI  - Envelope glycoproteins from human immunodeficiency virus types 1 and 2 and simian
      immunodeficiency virus can use human CCR5 as a coreceptor for viral entry and
      make direct CD4-dependent interactions with this chemokine receptor.
AB  - Several members of the chemokine receptor family have recently been identified as
      coreceptors, with CD4, for entry of human immunodeficiency virus type 1 (HIV-1)
      into target cells. In this report, we show that the envelope glycoproteins of
      several strains of HIV-2 and simian immunodeficiency virus (SIV) employ the same
      chemokine receptors for infection. Envelope glycoproteins from HIV-2 use CCR5 or
      CXCR4, while those from several strains of SIV use CCR5. Our data indicate also
      that some viral envelopes can use more than one coreceptor for entry and suggest
      that some of these coreceptors remain to be identified. To further understand how
      different envelope molecules use CCR5 as an entry cofactor, we show that soluble
      purified envelope glycoproteins (SU component) from CCR5-tropic HIV-1, HIV-2, and
      SIV can compete for binding of iodinated chemokine to CCR5. The competition is
      dependent on binding of the SU glycoprotein to cell surface CD4 and implies a
      direct interaction between envelope glycoproteins and CCR5. This interaction is
      specific since it is not observed with SU glycoprotein from a CXCR4-tropic virus
      or with a chemokine receptor that is not competent for viral entry (CCR1). For
      HIV-1, the interaction can be inhibited by antibodies specific for the V3 loop of
      SU. Soluble CD4 was found to potentiate binding of the HIV-2 ST and SIVmac239
      envelope glycoproteins to CCR5, suggesting that a CD4-induced conformational
      change in SU is required for subsequent binding to CCR5. These data suggest a
      common fundamental mechanism by which structurally diverse HIV-1, HIV-2, and SIV
      envelope glycoproteins interact with CD4 and CCR5 to mediate viral entry.

PMID- 9261350
TI  - Evolution of the human immunodeficiency virus type 1 subtype-specific V3 domain
      is confined to a sequence space with a fixed distance to the subtype consensus.
AB  - Human immunodeficiency virus type 1 (HIV-1) strains can be separated into genetic
      subtypes based on phylogenetic analysis of the envelope gene. Once it had been
      shown that population-wide intrasubtype genetic variation of HIV-1 strains
      increases in the course of the AIDS epidemic, it remained uncertain whether HIV-1
      subtypes are phenotypic entities spreading as distinct virus populations. To
      examine this, we applied Eigen's concepts of sequence geometry and fitness
      topography to the analysis of intrasubtype evolution of the gp120 V3 domain of
      HIV-1 subtypes A, B, C, and D in the course of the global AIDS epidemic. We
      observed that despite the high evolution rate of HIV-1, the nonsynonymous
      distances to the subtype consensus of sequences obtained early in the epidemic
      are similar to those obtained more than 10 years later, in contrast to the
      synonymous distances, which increased steadily over time. For HIV-1 subtype B, we
      observed that the evolution rate of the individual sequences is independent of
      their distance from the subtype B consensus, but for the individual sequences
      most distant from the consensus evolution away from the consensus is constrained.
      As a result, individual HIV-1 genomes fluctuate within a sequence space with
      fixed distance to the subtype consensus. Our findings suggest that the evolution
      of the V3 domain of HIV-1 subtypes A, B, C, and D is confined to an area in
      sequence space within a fixed distance to the consensus of a respective subtype.
      This in turn indicates that each HIV-1 subtype is a distinct viral quasispecies
      that is well adapted to the present environment, able to maintain its identity in
      the V3 region over time, and unlikely to merge during progression of the AIDS
      epidemic.

PMID- 9261349
TI  - The potent enhancer activity of the polycythemic strain of spleen focus-forming
      virus in hematopoietic cells is governed by a binding site for Sp1 in the
      upstream control region and by a unique enhancer core motif, creating an
      exclusive target for PEBP/CBF.
AB  - The polycythemic strain of the spleen focus-forming virus (SFFVp) contains the
      most potent murine retroviral enhancer configuration known so far for gene
      expression in myeloerythroid hematopoietic cells. In the present study, we mapped
      two crucial elements responsible for the high activity of the SFFVp enhancer to
      an altered upstream control region (UCR) containing a GC-rich motif (5'-GGGCGGG
      3') and to a unique enhancer core (5'-TGCGGTC-3'). Acquisition of these motifs
      accounts for half of the activity of the complete retroviral enhancer in
      hematopoietic cells, irrespective of the developmental stage or lineage.
      Furthermore, the UCR motif contains the major determinant for the enhancer
      activity of SFFVp in embryonic stem (ES) cells. Using electrophoretic mobility
      shift assays, we show that the UCR of SFFVp, but not of Friend murine leukemia
      virus, is targeted by the ubiquitous transcriptional activator, Sp1. The core
      motif of SFFVp creates a specific and high-affinity target for polyomavirus
      enhancer binding protein/core binding factor (PEBP/CBF) and excludes access of
      CAAT/enhancer binding protein. Cotransfection experiments with ES cells imply
      that PEBP/CBF cooperates with the neighboring element, LVb (the only conserved
      Ets consensus in the SFFVp enhancer), and that the Sp1 motif in the UCR
      stimulates transactivation through the Ets-PEBP interaction. Putative secondary
      structures of the retroviral enhancers are proposed based on these data.

PMID- 9261351
TI  - Nuclear import, virion incorporation, and cell cycle arrest/differentiation are
      mediated by distinct functional domains of human immunodeficiency virus type 1
      Vpr.
AB  - The vpr gene product of human immunodeficiency virus type 1 (HIV-1) is a virion
      associated protein that is essential for efficient viral replication in
      monocytes/macrophages. Vpr is primarily localized in the nucleus when expressed
      in the absence of other viral proteins. Vpr is packaged efficiently into viral
      particles through interactions with the p6 domain of the Gag precursor
      polyprotein p55gag. We developed a panel of expression vectors encoding Vpr
      molecules mutated in the amino-terminal helical domain, leucine-isoleucine (LR)
      domain, and carboxy-terminal domain to map the different functional domains and
      to define the interrelationships between virion incorporation, nuclear
      localization, cell cycle arrest, and differentiation functions of Vpr. We
      observed that substitution mutations in the N-terminal domain of Vpr impaired
      both nuclear localization and virion packaging, suggesting that the helical
      structure may play a vital role in modulating both of these biological
      properties. The LR domain was found to be involved in the nuclear localization of
      Vpr. In contrast, cell cycle arrest appears to be largely controlled by the C
      terminal domain of Vpr. The LR and C-terminal domains do not appear to be
      essential for virion incorporation of Vpr. Interestingly, we found that two Vpr
      mutants harboring single amino acid substitutions (A30L and G75A) retained the
      ability to translocate to the nucleus but were impaired in the cell cycle arrest
      function. In contrast, mutation of Leu68 to Ser resulted in a protein that
      localizes in the cytoplasm while retaining the ability to arrest host cell
      proliferation. We speculate that the nuclear localization and cell cycle arrest
      functions of Vpr are not interrelated and that these functions are mediated by
      separable putative functional domains of Vpr.

PMID- 9261352
TI  - pol gene diversity of five human immunodeficiency virus type 1 subtypes: evidence
      for naturally occurring mutations that contribute to drug resistance, limited
      recombination patterns, and common ancestry for subtypes B and D.
AB  - Naturally occurring mutations in the polymerase gene of human immunodeficiency
      virus type 1 (HIV-1) have important implications for therapy and the outcome of
      clinical studies. Using 42 virus isolates obtained from the UNAIDS sample
      collection, we analyzed the protease (99 amino acids [aa]) and the first 297 aa
      of reverse transcriptase (RT) coding regions. Based on the V3 sequence analysis,
      the collection includes subtype A (n = 5), subtype B (n = 12), subtype C (n = 1),
      subtype D (n = 11), and subtype E (n = 13) viruses. Of the 42 protease genes, 37
      contained naturally occurring mutations at positions in the gene that contribute
      to resistance to protease inhibitors (indinavir, saquinavir, ritonavir, and
      nelfinavir) in clade B isolates. The phenotypic effect of these substitutions in
      non-B isolates is unclear. The The 5'half RT coding region of the 42 isolates was
      found to be less variable, although 19 of the 42 RT sequences contained amino
      acid substitutions known to contribute to nucleoside and/or nonnucleoside drug
      resistance. Since the virus isolates were obtained in 1992, it is unlikely that
      the infected subjects received protease inhibitors, but we found evidence that
      one subject acquired a zidovudine (AZT)-resistant HIV-1 strain from a contact who
      had received AZT. Phylogenetic analysis identified five subtype pol clusters: A,
      B, C, D, and A'. Comparison of env and pol sequences of the same viruses showed
      no more recombination events than were already identified on the basis of gag/env
      comparison (M. Cornelissen, G. Kampinga, F. Zorgdrager, J. Goudsmit, and the
      UNAIDS Network for HIV Isolation and Characterization, J. Virol. 70:8209-8212,
      1996). In one of the known recombinants, a crossover site between subtypes A and
      C could be identified, and in another, a crossover site could not be identified
      due to lack of a reference subtype F pol sequence. We analyzed the ds/da ratio of
      gag, pol, and env sequences of 35 isolates, excluding the recombinants. Our
      analysis showed that gag and pol are subjected to purifying selection with an
      average ds/da ratio above 1, independent of the subtype and in contrast with V3
      (ds/da approximately 1). Based on the low ds/da ratio of the intergroup analysis
      of A/E and B/D gag and pol sequences, we analyzed the evolutionary relation
      between subtypes B and D in more detail by constructing separate phylogenetic
      trees for synonymous and nonsynonymous substitutions. Our analysis suggests a
      common ancestry for subtypes B and D that is distinct from that of subtypes A and
      E.

PMID- 9261353
TI  - Placental trophoblasts resist infection by multiple human immunodeficiency virus
      (HIV) type 1 variants even with cytomegalovirus coinfection but support HIV
      replication after provirus transfection.
AB  - Whether cell-free human immunodeficiency virus type 1 (HIV-1) can productively
      infect placental trophoblasts (which in turn could transmit the virus into the
      fetal circulation) is controversial but essential to know for the evaluation of
      alternative routes (such as cell-mediated infection or trophoblast damage). We
      have addressed infection factors such as cell purity, source, culture methods,
      and activation states as well as virus variant and detection methods to
      conclusively determine the outcome of trophoblast challenge by free virus. Pure
      (> 99.98%) populations of trophoblasts from 11 different placentas were
      challenged at a multiplicity of infection (MOI) as high as 6 with five different
      HIV-1 variants, three of which are non-syncytium-forming, macrophage-tropic
      isolates from infected infants, with and without coinfection with
      cytomegalovirus; these preparations were monitored for productive infection for
      up to 3 weeks after challenge by five different criteria, the most sensitive of
      which were cocultivation with target cells that can detect virus at an MOI of 10(
      7) and HIV DNA PCR that detects 30 virus copies per 10(5) cells. Infection was
      never detected. However, molecularly cloned T-cell (pNL4-3)- and macrophage
      (pNLAD8)-tropic provirus plasmids, when transfected into primary trophoblasts,
      yielded productive infections, indicating that trophoblasts do not suppress late
      stage virus replication and assembly. Because of the purity of the trophoblast
      preparations, the extended length of the infection culture period, the number of
      trophoblast preparations and virus types examined, the sensitivity of the
      bioassays and molecular detection assays, and the observations that trophoblasts
      can support virus replication from provirus, the results of this study strongly
      argue that free virus cannot infect primary villous trophoblasts.

PMID- 9261354
TI  - In vitro study of the NS2-3 protease of hepatitis C virus.
AB  - Processing at the C terminus of the NS2 protein of hepatitis C virus (HCV) is
      mediated by a virus-encoded protease which spans most of the NS2 protein and part
      of the NS3 polypeptide. In vitro cotranslational cleavage at the 2-3 junction is
      stimulated by the presence of microsomal membranes and ultimately results in the
      membrane insertion of the NS2 polypeptide. To characterize the biochemical
      properties of this viral protease, we have established an in vitro assay whereby
      the NS2-3 protease of HCV BK can be activated posttranslationally by the addition
      of detergents. The cleavage proficiency of several deletion and single point
      mutants was the same as that observed with microsomal membranes, indicating that
      the overall sequence requirements for proper cleavage at this site are maintained
      even under these artificial conditions. The processing efficiency of the NS2-3
      protease varied according to the type of detergent used and its concentration.
      Also, the incubation temperature affected the cleavage at the 2-3 junction. The
      autoproteolytic activity of the NS2-3 protease could be inhibited by alkylating
      agents such as iodoacetamide and N-ethylmaleimide. Metal chelators such as EDTA
      and phenanthroline also inhibited the viral enzyme. The EDTA inhibition of NS2-3
      cleavage could be reversed, at least in part, by the addition of ZnCl2 and CdCl2.
      Among the common protease inhibitors tested, tosyl phenylalanyl chloromethyl
      ketone and soybean trypsin inhibitor inactivated the NS2-3 protease. By means of
      gel filtration analysis, it was observed that the redox state of the reaction
      mixture greatly influenced the processing efficiency at the 2-3 site and that
      factors present in the rabbit reticulocyte lysate, wheat germ extract, and HeLa
      cell extract were required for efficient processing at this site. Thus, the in
      vitro assay should allow further characterization of the biochemical properties
      of the NS2-3 protease of HCV and the identification of host components that
      contribute to the efficient processing at the 2-3 junction.

PMID- 9261355
TI  - Role of preterminal protein processing in adenovirus replication.
AB  - Preterminal protein (pTP), the protein primer for adenovirus DNA replication, is
      processed at two sites by the virus-encoded protease to yield mature terminal
      protein (TP). Here we demonstrate that processing to TP, via an intermediate
      (iTP), is conserved in all serotypes sequenced to date; and in determining the
      sites cleaved in Ad4 pTP, we extend the previously published substrate
      specificity of human adenovirus proteases to include a glutamine residue at P4.
      Furthermore, using monoclonal antibodies raised against pTP, we show that
      processing to iTP and TP are temporally separated in the infectious cycle, with
      processing to iTP taking place outside the virus particles. In vitro and in vivo
      studies of viral DNA replication reveal that iTP can act as a template for
      initiation and elongation and argue against a role for virus-encoded protease in
      switching off DNA replication. Virus DNA with TP attached to its 5' end (TP-DNA)
      has been studied extensively in in vitro DNA replication assays. Given that in
      vivo pTP-DNA, not TP-DNA, is the template for all but the first round of
      replication, the two templates were compared in vitro and shown to have different
      properties. Immunofluorescence studies suggest that a region spanning the TP
      cleavage site is involved in defining the subnuclear localization of pTP.
      Therefore, a likely role for the processing of pTP-DNA is to create a distinct
      template for early transcription (TP-DNA), while the terminal protein moiety, be
      it TP or pTP, serves to guide the template to the appropriate subcellular
      location through the course of infection.

PMID- 9261356
TI  - The catalytic subunit of the DNA polymerase of herpes simplex virus type 1
      interacts specifically with the C terminus of the UL8 component of the viral
      helicase-primase complex.
AB  - The herpes simplex virus type 1 (HSV-1) UL8 DNA replication protein is a
      component of a trimeric helicase-primase complex. Sixteen UL8-specific monoclonal
      antibodies (MAbs) were isolated and characterized. In initial immunoprecipitation
      experiments, one of these, MAb 804, was shown to coprecipitate POL, the catalytic
      subunit of the HSV-1 DNA polymerase, from extracts of insect cells infected with
      recombinant baculoviruses expressing the POL and UL8 proteins. Coprecipitation of
      POL was dependent on the presence of UL8 protein. Rapid enzyme-linked
      immunosorbent assays (ELISAs), in which one protein was bound to microtiter wells
      and binding of the other protein was detected with a UL8- or POL-specific MAb,
      were developed to investigate further the interaction between the two proteins.
      When tested in the ELISAs, five of the UL8-specific MAbs consistently inhibited
      the interaction, raising the possibility that these antibodies act by binding to
      epitopes at or near a site(s) on UL8 involved in its interaction with POL. The
      epitopes recognized by four of the inhibitory MAbs were approximately located by
      using a series of truncated UL8 proteins expressed in mammalian cells. Three of
      these MAbs recognized an epitope near the C terminus of UL8, which was subjected
      to fine mapping with a series of overlapping peptides. The C-terminal peptides
      were then tested in the ELISA for their ability to inhibit the POL-UL8
      interaction: the most potent exhibited a 50% inhibitory concentration of
      approximately 5 microM. Our findings suggest that the UL8 protein may be involved
      in recruiting HSV-1 DNA polymerase into the viral DNA replication complex and
      also identify a potential new target for antiviral therapy.

PMID- 9261357
TI  - A 45,000-M(r) glycoprotein in the Sendai virus envelope triggers virus-cell
      fusion.
AB  - Sendai virus envelopes devoid of hemagglutinin-neuraminidase but containing the
      fusion protein (F-virosomes) were prepared. F-virosomes exhibited discernible
      serine protease activity at neutral pH. Electrophoretic analysis of the protein
      profile of the F-virosomes under nonreducing conditions, by both sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and isoelectric focusing, led to the
      identification of a previously unknown glycoprotein with a relative molecular
      weight of 45,000 (45K protein) associated with the F protein. The identity of the
      45K protein, as distinct from F protein, was established by Western blot analysis
      with F- and 45K-specific antibodies. This 45K protein forms a nexus with the F
      protein through noncovalent hydrophobic interactions, as proved by its
      sensitivity to urea treatment, and it is essential for the proteolytic activity
      of the F-virosomes as well as for the fusion of the viral envelope with host cell
      membrane. N-terminal sequence analysis (first 11 amino acids) of this protein
      showed strong homology (> 90%) to flavivirus NS3 serine proteases but no
      similarity to any of the Sendai viral proteins. On the basis of the N-terminal
      sequence, oligonucleotides were designed corresponding to the sense and antisense
      DNA sequences. Dot blot hybridization and primer extension with these
      oligonucleotides with the viral and the host genome confirmed the host origin of
      this protein. Further, the limited proteolytic digestion of the target membrane
      resulted in significant inhibition of viral fusion with it. On the basis of these
      results, we postulate a model for the molecular mechanism of F protein-induced
      membrane fusion, which may provide a rationale for other paramyxoviruses.

PMID- 9261358
TI  - Shared usage of the chemokine receptor CXCR4 by the feline and human
      immunodeficiency viruses.
AB  - Feline immunodeficiency virus (FIV) induces a disease state in the domestic cat
      that is similar to AIDS in human immunodeficiency virus (HIV)-infected
      individuals. As with HIV, FIV can be divided into primary and cell culture
      adapted isolates. Adaptation of FIV to replicate and form syncytia in the
      Crandell feline kidney (CrFK) cell line is accompanied by an increase in the net
      charge of the V3 loop of the envelope glycoprotein, mirroring the changes
      observed in the V3 loop of HIV gp120 with the switch from a non-syncytium
      inducing phenotype to a syncytium-inducing phenotype. These data suggest a common
      mechanism of infection with FIV and HIV. In this study, we demonstrate that cell
      culture-adapted strains of FIV are able to use the alpha-chemokine receptor CXCR4
      for cell fusion. Following ectopic expression of human CXCR4 on nonpermissive
      human cells, the cells are able to fuse with FIV-infected feline cells. Moreover,
      fusion between FIV-infected feline cells and CXCR4-transfected human cells is
      inhibited by both anti-CXCR4 and anti-FIV antibodies. cDNAs encoding the feline
      CXCR4 homolog were cloned from both T-lymphoblastoid and kidney cell lines.
      Feline CXCR4 displayed 94.9% amino acid sequence identity with human CXCR4 and
      was found to be expressed widely on cell lines susceptible to infection with cell
      culture-adapted strains FIV. Ectopic expression of feline CXCR4 on human cells
      rendered the cells susceptible to FIV-dependent fusion. Moreover, feline CXCR4
      was found to be as efficient as human CXCR4 in supporting cell fusion between CD4
      expressing murine fibroblast cells and either HIV type 1 (HIV-1) or HIV-2 Env
      expressing human cells. Previous studies have demonstrated that feline cells
      expressing human CD4 are not susceptible to infection with HIV-1; therefore,
      further restrictions to HIV-1 Env-dependent fusion may exist in feline cells. As
      feline and human CXCR4 support both FIV- and HIV-dependent cell fusion, these
      results suggest a close evolutionary link between FIV and HIV and a common
      mechanism of infection involving an interaction between the virus and a member of
      the seven-transmembrane domain chemokine receptor family of molecules.

PMID- 9261359
TI  - A splicing enhancer in the 3'-terminal c-H-ras exon influences mRNA abundance and
      transforming activity.
AB  - Analysis of cDNA clones previously identified an optional intron in the 3'
      untranslated region of the human H-ras gene. A possible correlation was observed
      between failure to remove this intron and overexpression of the gene, suggesting
      that splicing of the intron may require a specific titrable factor. The splicing
      signals at the end of the intron deviate from the consensus and may be
      inefficient, but we noticed that the adjacent exon downstream has a purine-rich
      region reminiscent of purine-rich splicing enhancers in other genes that
      stimulate the removal of weak, flanking introns. We show here that the purine
      rich region of H-ras has splicing-enhancer activity in the homologous as well as
      a heterologous context. Interestingly, although the affected intron is outside
      the coding region, inversion or deletion of the enhancer reduced the transforming
      activity of oncogenic H-ras alleles severalfold. Experiments with corresponding
      cDNA constructs suggested that this is not a consequence of the altered
      structures of the mRNAs produced when the enhancer is inverted or deleted.
      Instead, we propose that the region controls an additional pre-mRNA processing
      event besides splicing of the terminal intron. Our work indicates that the purine
      rich region may play an important role in the control of H-ras activity.

PMID- 9261360
TI  - Isolation and characterization of human papillomavirus type 6-specific T cells
      infiltrating genital warts.
AB  - The potential role of T cells in the control of human papillomavirus type 6 (HPV
      6) infections is an appealing premise, but their actual role has been sparsely
      investigated. Since HPV-6 infections are confined to the epithelium, such an
      investigation should focus on the T cells present at the site of infection (i.e.,
      the warts). Therefore, we isolated wart-infiltrating lymphocytes (WIL) from
      patients with clinically diagnosed anogenital warts. These WIL were characterized
      by their phenotype and their specificity for E7 and L1 proteins of HPV-6. The
      phenotype of WIL varied drastically from patient to patient, as determined by
      their expression of CD4, CD8, T-cell receptor alpha/beta chain (TCR alpha beta),
      and TCR gamma delta. Despite this heterogeneity in phenotype, HPV-6 E7 and/or L1
      specific WIL, as determined by lymphoproliferation, could be isolated from more
      than 75% of the patients studied. Among all L1 peptides recognized by WIL,
      peptides 311-330 and 411-430 were the most consistently detected, with seven of
      nine patients for whom L1 peptide reactivity was observed responding to at least
      one of them. Moreover, the HPV-6 epitopic peptides recognized by WIL differed to
      some extent from those recognized by peripheral T cells.

PMID- 9261362
TI  - Mapping promoter regions that are hypersensitive to methylation-mediated
      inhibition of transcription: application of the methylation cassette assay to the
      Epstein-Barr virus major latency promoter.
AB  - Methylation-associated transcriptional repression is recognized in many settings
      and may play a role in normal differentiation and in tumorigenesis. Both sequence
      specific and nonspecific mechanisms have been elaborated. Recently, we have
      presented evidence that methylation-associated inhibition of the Epstein-Barr
      virus (EBV) major latency promoter (BamHI C promoter or Cp) in Burkitt's lymphoma
      and Hodgkin's disease may play an important role in the pathogenesis of these
      tumors by protecting them from CD8+ cytotoxic T-cell immunosurveillance. The
      mechanism of transcriptional repression may relate to specific inhibition of the
      binding of a cellular transcription factor by methylation. To dissect the viral
      promoter with regard to transcriptional sensitivity to methylation, we have
      devised an assay that allows the methylation of discrete regions of reporter
      plasmids. During the course of the assay, methylation patterns appeared to be
      stable; there was no evidence of either spread or reversal of the imposed
      methylation pattern. Application of the assay to the 3.8-kb region upstream of
      the major EBV latency promoter with natural Cp reporter plasmids showed that
      sensitivity to methylation is not homogeneously distributed but is concentrated
      in two discrete regions. The first of these methylation-hypersensitive regions
      (MHRI) is the previously identified EBNA-2 response element, which includes the
      methylation-sensitive CBF2 binding site. The second (MHRII) is a sequence further
      downstream whose potential role in methylation-mediated transcriptional
      repression had been previously unsuspected. In chimeric enhancer/promoter
      plasmids, methylation of this downstream region was sufficient to virtually
      abolish simian virus 40 enhancer-driven transcription. Further dissection
      indicated that methylation of the EBNA-2 response element (MHRI) was sufficient
      to abolish EBNA-2-mediated Cp activity while methylation of a region including
      the EBNA-2 response element and downstream sequence (MHRI and MHRII) was
      sufficient to abolish all Cp-mediated reporter activity, including that driven by
      the EBNA-1-dependent enhancer in the origin of plasmid replication, oriP.

PMID- 9261361
TI  - Translation elongation factor-1 alpha interacts with the 3' stem-loop region of
      West Nile virus genomic RNA.
AB  - The conserved 3'-terminal stem-loop (3' SL) of the West Nile virus (WNV) genomic
      RNA was previously used to probe for cellular proteins that may be involved in
      flavivirus replication and three cellular proteins were detected that
      specifically interact with the WNV 3' SL RNA (J. L. Blackwell and M. A. Brinton,
      J. Virol. 69:5650-5658, 1995). In this study, one of these cellular proteins was
      purified to apparent homogeneity by ammonium sulfate precipitation and liquid
      chromatography. Amino acid sequence Western blotting, and supershift analyses
      identified the cellular protein as translation elongation factor-1 alpha (EF-1
      alpha). Competition gel mobility shift assays demonstrated that the interaction
      between EF-1 alpha and WNV 3' SL RNA was specific. Dephosphorylation of EF-1
      alpha by calf intestinal alkaline phosphatase inhibited its binding to WNV 3' SL
      RNA. The apparent equilibrium dissociation constant for the interaction between
      EF-1 alpha and WNV 3' SL RNA was calculated to be 1.1 x 10(-9) M. Calculation of
      the stoichiometry of the interaction indicated that one molecule of EF-1 alpha
      binds to each molecule of WNV 3' SL RNA. Using RNase footprinting and
      nitrocellulose filter binding assays, we detected a high-activity binding site on
      the main stem of the WNV 3' SL RNA. Interaction with EF-1 alpha at the high
      activity binding site was sequence specific, since nucleotide substitution in
      this region reduced the binding activity of the WNV 3' SL RNA for EF-1 alpha by
      approximately 60%. Two low-activity binding sites were also detected, and each
      accounted for approximately 15 to 20% of the binding activity. Intracellular
      association between the host protein and the viral RNA was suggested by
      coimmunoprecipitation of WNV genomic RNA and EF-1 alpha, using an anti-EF-1 alpha
      antibody.

PMID- 9261364
TI  - The hepatitis C virus NS4A protein: interactions with the NS4B and NS5A proteins.
AB  - Hepatitis C virus encodes a large polyprotein precursor that is proteolytically
      processed into at least 10 distinct products, in the order NH2-C-E1-E2-p7-NS2-NS3
      NS4A-NS4B-NS5A-NS5B -COOH. A serine proteinase encoded in the N-terminal 181
      residues of the NS3 nonstructural protein is responsible for cleavage at four
      sites (3/4A, 4A/4B, 4B/5A, and 5A/5B) in the nonstructural region. NS4A, a 54
      residue nonstructural protein which forms a stable complex with the NS3
      proteinase, is required as a cofactor for cleavage at the 3/4A and 4B/5A sites
      and enhances processing at the 4A/4B and 5A/5B sites. Recently reported crystal
      structures demonstrated that NS4A forms an integral part of the NS3 serine
      proteinase. In this report, we present evidence that NS4A forms a nonionic
      detergent-stable complex with the NS4B5A polyprotein substrate, which may explain
      the requirement of NS4A for the 4B/5A cleavage. Isoleucine-29 of NS4A, which has
      been previously shown to be essential for its proteinase cofactor activity and
      formation of the NS3 complex, was found to be important for the interaction
      between NS4A and the NS4B5A substrate. In addition, two more hydrophobic residues
      in the NS4A central region (valine-23 and isoleucine-25) were also shown to be
      essential for the cofactor activity and for the interaction with either the NS3
      proteinase or the NS4B5A polyprotein substrate. Finally, the possible mechanisms
      by which these viral proteins interact with each other are discussed.

PMID- 9261363
TI  - Characterization of pseudorabies virus mutants expressing carboxy-terminal
      truncations of gE: evidence for envelope incorporation, virulence, and
      neurotropism domains.
AB  - Glycoprotein E (gE) gene of pseudorabies virus (PRV) is conserved among diverse
      alphaherpesviruses and therefore is predicted to be important for virus survival.
      gE contributes to viral spread from cell to cell in a variety of hosts and is
      responsible, in part, for increased virulence or pathogenesis of the virus.
      Virulence and spread mediated by gE are thought to be highly correlated. We
      initiated this study to explore the hypothesis that these two phenotypes might
      reflect separate functions of the gE protein. We did so by focusing on the role
      of the gE carboxy terminus in neuronal spread. Viruses harboring nonsense
      mutations affecting the expression of the gE cytoplasmic domain had several
      notable phenotypes. First, the truncated gE proteins expressed from these mutants
      are not found in virion envelopes. Second, the mutants retain the ability to
      spread to all retinorecipient regions of the rodent brain after retinal infection
      of rats. Third, the mutants have the reduced virulence phenotype of a gE deletion
      mutant in rats. Finally, the mutants have distinct plaque-size phenotypes on MDBK
      cells but not PK15 cells. Based on these observations, we suggest that gE
      mediated virulence and spread may reflect separate functions that are not
      mediated by gE on virus particles.

PMID- 9261365
TI  - Phosphorylation sites in polyomavirus large T antigen that regulate its function
      in viral, but not cellular, DNA synthesis.
AB  - Polyomavirus large T antigen (large T) is a highly phosphorylated protein that
      can be separated by proteolysis into two domains that have independent function.
      A cluster of phosphorylation sites was found in the protease-sensitive region
      connecting the N-terminal and C-terminal domains. Edman degradation of 32P
      labeled protein identified serines 267, 271, and 274 and threonine 278 as sites
      of phosphorylation. Analysis of site-directed mutants confirmed directly that
      residues 271, 274, and 278 were phosphorylated. Threonine 278, shown here to be
      phosphorylated by cyclin/cyclin-dependent kinase activity, is required for viral
      DNA replication in either the full-length large T or C-terminal domain context.
      The serine phosphorylations are unimportant in the C-terminal domain context even
      though their mutations activates viral DNA replication in full-length large T.
      This finding suggests that these sites may function in relating the two domains
      to each other. Although the phosphorylation sites were involved in viral DNA
      replication, none was important for the ability of large T to drive cellular DNA
      replication as measured by bromodeoxyuridine incorporation, and they did not
      affect large T interactions with the Rb tumor suppressor family.

PMID- 9261366
TI  - Cyclin-dependent kinase regulation of the replication functions of polyomavirus
      large T antigen.
AB  - The amino-terminal portion of polyomavirus (Py) large T antigen (T Ag) contains
      two phosphorylation sites, at T187 and T278, which are potential substrates for
      cyclin-dependent kinases (CDKs). Our experiments were designed to test whether
      either or both of these sites are involved in the origin DNA (ori DNA)
      replication function of Py T Ag. Mutations were generated in Py T Ag whereby
      either or both threonines were replaced with alanine, generating T187A, T278A,
      and double-mutants (DM [T187A T278A]) mutant T Ags. We found that the Py ori DNA
      replication functions of T278A and DM, but not T187A, mutant T Ags were abolished
      both in vivo and in vitro. Consistent with this finding, it was shown that the
      ori DNA binding and unwinding activities of mutant T278A Py T Ag were greatly
      impaired. Moreover, whereas wild-type Py T Ag is an efficient substrate for
      phosphorylation by cyclin A-CDK2 and cyclin B-cdc2 complexes, it is
      phosphorylated poorly by a cyclin E-CDK2 complex. In contrast to mutant T187A,
      which behaved similarly to the wild-type protein, T278A was only weakly
      phosphorylated by cyclin B-cdc2. These data thus suggest that T278 is an
      important site on Py T Ag for phosphorylation by CDKs and that loss of this site
      leads to its various defects in mediating ori DNA replication. S- and G2-phase
      specific CDKs, but not a G1-specific CDK, can phosphorylate wild-type T Ag, which
      suggests yet another reason why DNA tumor viruses require actively cycling host
      cells.

PMID- 9261368
TI  - Modulation of RANTES production by human cytomegalovirus infection of
      fibroblasts.
AB  - Chemokines play a major role in inflammatory responses and affect hematopoiesis
      both negatively and positively. We show that fresh isolates and laboratory
      strains (Towne and Ad-169) of human cytomegalovirus (HCMV) induce production of
      the CC chemokine RANTES in fibroblasts. Induction of extracellular RANTES
      production occurred as early as 8 h after infection, peaked around 24 h after
      infection, and was almost undetectable by 48 and 72 h. Upregulation occurred in
      the absence of viral DNA synthesis, suggesting that it was due to immediate-early
      early HCMV gene expression. CMV infection stimulated RANTES transcription, since
      reverse transcription-PCR detected a sharp increase in RANTES RNA which persisted
      even when extracellular RANTES was no longer detected. Induction of RANTES in
      fibroblasts was not due to prior induction of tumor necrosis factor alpha or
      interleukin 1 beta. Down-regulation required an active viral genome. Decrease of
      RANTES in culture supernatants may be associated with the appearance of the HCMV
      CC chemokine receptor US28, since we show that this gene is transcribed as early
      as 8 h after infection. Modulation of CC chemokine production early during CMV
      infection might have a regulatory effect on viral replication, as well as affect
      immune surveillance.

PMID- 9261367
TI  - Inhibition of human immunodeficiency virus type 1 replication in vitro by a novel
      combination of anti-Tat single-chain intrabodies and NF-kappa B antagonists.
AB  - Human immunodeficiency virus type 1 (HIV-1) Tat, an early regulatory protein that
      is critical for viral gene expression and replication, transactivates the HIV-1
      long terminal repeat (LTR) via its binding to the transactivation response
      element (TAR) and, along with other cellular factors, increases viral
      transcription initiation and elongation. Tat also superactivates the HIV-1
      promoter through a TAR-independent mechanism, including tumor necrosis factor
      alpha-induced and protein kinase C (PKC)-dependent activation of NF-kappa B, and
      inhibitors of Tat and NF-kappa B cooperatively down-regulate this Tat-mediated
      LTR superactivation. In this study, a combined pharmacologic and genetic strategy
      using two PKC (NF-kappa B) inhibitors, pentoxifylline (PTX) and Go-6976, and a
      stably expressed anti-Tat single-chain intracellular antibody (sFv intrabody) was
      employed to obtain cooperative inhibition of both HIV-1 LTR-driven gene
      expression and HIV-1 replication. Treatment of cells with PTX and Go-6976
      resulted in cooperative inhibition of both HIV-1 LTR-driven gene expression and
      HIV-1 replication. In addition, the combined use of anti-Tat sFv intrabodies and
      the two NF-kappa B inhibitors retained the virus in the latent state for as long
      as 45 days. The combined treatment resulted in more durable inhibition of HIV-1
      replication than was seen with the NF-kappa B inhibitors alone or the anti-Tat
      sFv intrabodies alone. Together, these results suggest that in future clinical
      gene therapy trials, a combined pharmacologic and genetic strategy like the one
      reported here may improve the survival of transduced cells and prolong clinical
      benefit.

PMID- 9261369
TI  - Identification of GB virus C variants by phylogenetic analysis of 5'-untranslated
      and coding region sequences.
AB  - Phylogenetic analysis of 44 GB virus C (GBV-C) 5'-untranslated region (5'-UTR)
      sequences from 37 individuals suggested the presence of GBV-C genotypes (A. S.
      Muerhoff, J. N. Simons, T. P. Leary, J. C. Erker, M. L. Chalmers, T. J. Pilot
      Matias, G. J. Dawson, S. M. Desai, and I. K. Mushahwar, J. Hepatol. 25:379-384,
      1996) that correlated with geographic origin: type 1, 2a and 2b, and 3 isolates
      are found predominantly in West Africa, the United States and Europe, and Japan,
      respectively. We have extended our analysis to include 5'-UTR sequences from 129
      globally distributed GBV-C isolates and sequences from the second envelope
      protein (E2) gene and nonstructural (NS) regions 3 and 5b from a subset of these
      isolates. Bootstrap analysis of a 157-nucleotide segment of the 5'-UTR from 129
      sequences provided weak support for the existence of the four major groups of GBV
      C isolates previously described, although phylogenetic analysis of a 374
      nucleotide segment of the 5'-UTR from 83 isolates provided stronger support.
      Thus, the groups of GBV-C variants previously identified upon analysis of the
      entire 5'-UTR can be distinguished by analysis of the shorter, 374-nucleotide
      region from the 5'-UTR. In contrast, independent analysis of the E2, NS3, or NS5b
      region sequences does not identify groups of GBV-C variants that correlate with
      geographic origin. However, bootstrap analysis of these coding sequences, when
      linked to form colinear sequences, demonstrates that longer coding regions can
      produce GBV-C groupings that are similar to that determined from 5'-UTR sequence
      analysis. The inability to distinguish between GBV-C variants by using small
      segments of coding sequence suggests that the GBV-C genome is constrained. As a
      result of these constraints, there is a high degree of nucleotide and amino acid
      sequence conservation between isolates from widely separated geographic areas.
      Hence, substitutions at many nucleotide positions are not tolerated, so that
      substitutions at the positions which can change are saturated, thereby obscuring
      the evolutionary relationships.

PMID- 9261370
TI  - Simian immunodeficiency virus variants with differential T-cell and macrophage
      tropism use CCR5 and an unidentified cofactor expressed in CEMx174 cells for
      efficient entry.
AB  - The recent identification of coreceptors that mediate efficient entry of human
      immunodeficiency virus type 1 (HIV-1) suggests new therapeutic and preventive
      strategies. We analyzed simian immunodeficiency virus (SIV) entry cofactors to
      investigate whether the macaque SIV model can be used as an experimental model to
      evaluate these strategies. Similar to primary HIV-1 isolates, a well
      characterized molecular clone, SIVmac239, which replicates poorly but efficiently
      enters into rhesus alveolar macrophages and an envelope variant,
      SIVmac239/316Env, with an approximately 1,000-fold-higher replicative capacity in
      macrophages used the beta-chemokine receptor CCR5 for efficient entry. The
      transmembrane portion of 316Env allowed low-level entry into cells expressing
      CCR1, CCR2B, and CCR3. A single amino acid substitution in the V3 loop of
      SIVmac239/316Env, 321P-->S, impaired the ability to enter into the T-B hybrid
      cell line CEMx174 but had relatively little effect on entry into primary cells
      and HOS.CD4 cells expressing CCR5. Although CEMx174 cells do not express CCR5,
      most SIVmac variants entered this hybrid cell line efficiently but did not enter
      the parental T-cell line CEM. It seems likely that CEMx174 cells express an as
      yet-unidentified, perhaps B-cell-derived cofactor which allows efficient entry of
      SIVmac.

PMID- 9261371
TI  - Primary structure of the alcelaphine herpesvirus 1 genome.
AB  - Alcelaphine herpesvirus 1 (AHV-1) causes wildebeest-associated malignant
      catarrhal fever, a lymphoproliferative syndrome in ungulate species other than
      the natural host. Based on biological properties and limited structural data, it
      has been classified as a member of the genus Rhadinovirus of the subfamily
      Gammaherpes-virinae. Here, we report on cloning and structural analysis of the
      complete genome of AHV-1 C500. The low GC content DNA (L-DNA) region of the
      genome consists of 130,608 bp with low (46.17%) GC content and marked suppression
      of CpG dinucleotide frequency. Like in herpesvirus saimiri, the prototype of the
      rhadinoviruses, the L-DNA is flanked by approximately 20 to 25 GC-rich (71.83%)
      high GC content DNA (H-DNA) repeats of 1,113 to 1,118 nucleotides. The analysis
      of the L-DNA sequence revealed 70 open reading frames (ORFs), 61 of which showed
      homology to other herpesviruses. The conserved ORFs are arranged in four blocks
      collinear to other Rhadinovirus genomes. These gene blocks are flanked by
      nonconserved regions containing ORFs without similarities to known herpesvirus
      genes. Notably, a spliced reading frame with a coding capacity for a 199-amino
      acid protein is located in a position homologous to the transforming genes of
      herpesvirus saimiri at the left end of the L-DNA. A gene with homology to the
      semaphorin family is located adjacent to this. Despite common biological and
      epidemiological properties, AHV-1 differs significantly from herpesvirus saimiri
      with regard to cell homologous genes, probably using a different set of effector
      proteins to achieve a similar T-lymphocyte-transforming phenotype.

PMID- 9261373
TI  - Genetic determinant of rapid-onset B-cell lymphoma by avian leukosis virus.
AB  - Infection of 10 day-old chicken embryos with the recombinant avian leukosis virus
      (ALV) EU-8 induces a high incidence of rapid-onset B-cell lymphoma by insertional
      activation of the c-myb gene. LR-9, a related ALV with differences from EU-8 in
      the gag and pol genes, induces rapid-onset lymphoma at only a low incidence. To
      localize the viral determinant(s) responsible for this biologic difference, we
      constructed and tested a series of reciprocal chimeras between EU-8 and LR-9
      ALVs. The ability to induce rapid-onset lymphoma efficiently was localized to a
      925-nucleotide (nt) region of the EU-8 gag gene. Sequence analysis of the region
      revealed a 42-nt deletion in EU-8 relative to LR-9, as well as some single
      nucleotide changes. A mutant virus, delta LR-9, constructed by deleting these 42
      nt from LR-9, also induced rapid-onset lymphoma at a high frequency, confirming
      the biologic significance of this deletion. This deletion removed nt 735 to 776,
      which lies within a cis-acting RNA element that negatively regulates splicing
      (NRS). The deletion was shown to cause an increase in splicing efficiency, which
      may lead to increased production of a truncated myb gene product from an ALV-myb
      readthrough RNA.

PMID- 9261372
TI  - Minimal truncation of the c-myb gene product in rapid-onset B-cell lymphoma.
AB  - Oncogenic activation of c-myb by insertional mutagenesis has been implicated in
      rapid-onset B-cell lymphomas induced by the nonacute avian leukosis virus EU-8.
      In these tumors, proviruses are integrated either upstream of the c-myb coding
      region or within the first intron of c-myb. Tumors with either type of
      integration contained identical chimeric mRNAs in which the viral 5' splice site
      was juxtaposed to the 3' splice site of c-myb exon 2 and myb exon 1 was
      eliminated. Both classes of integrations generated truncated Myb proteins that
      were indistinguishable by Western analysis. In contrast to most other examples of
      c-myb activation, the truncation consisted of only 20 N-terminal amino acids and
      did not disrupt either the DNA binding domain near the N terminus or the negative
      regulatory domain near the C terminus of Myb. The significance of the 20-amino
      acid Myb truncation to tumorigenesis was tested by infection of chicken embryos
      with retroviral vectors expressing different myb gene products. While virus
      expressing either wild-type c-myb or c-myb mutated at the N-terminal casein
      kinase II sites was only weakly oncogenic at 10 weeks, the minimally truncated
      myb virus induced a high incidence of rapid-onset tumors, including B-cell
      lymphomas, sarcomas, and adenocarcinomas.

PMID- 9261374
TI  - Equine infectious anemia virus utilizes a YXXL motif within the late assembly
      domain of the Gag p9 protein.
AB  - We have previously demonstrated that the Gag p9 protein of equine infectious
      anemia virus (EIAV) is functionally homologous with Rous sarcoma virus (RSV) p2b
      and human immunodeficiency virus type 1 (HIV-1) p6 in providing a critical late
      assembly function in RSV Gag-mediated budding from transfected COS-1 cells (L. J.
      Parent et al., J. Virol. 69:5455-5460, 1995). In light of the absence of amino
      acid sequence homology between EIAV p9 and the functional homologs of RSV and HIV
      1, we have now designed an EIAV Gag-mediated budding assay to define the late
      assembly (L) domain peptide sequences contained in the EIAV p9 protein. The
      results of these particle budding assays revealed that expression of EIAV Gag
      polyprotein in COS-1 cells yielded extracellular Gag particles with a
      characteristic density of 1.18 g/ml, while expression of EIAV Gag polyprotein
      lacking p9 resulted in a severe reduction in the release of extracellular Gag
      particles. The defect in EIAV Gag polyprotein particle assembly could be
      corrected by substituting either the RSV p2b or HIV-1 p6 protein for EIAV p9.
      These observations demonstrated that the L domains of EIAV, HIV-1, and RSV were
      interchangeable in mediating assembly of EIAV Gag particles in the COS-1 cell
      budding assay. To localize the L domain of EIAV p9, we next assayed the effects
      of deletions and site-specific mutations in the p9 protein on its ability to
      mediate budding of EIAV Gag particles. Analyses of EIAV Gag constructs with
      progressive N-terminal or C-terminal deletions of the p9 protein identified a
      minimum sequence of 11 amino acids (Q20N21L22Y23P24D25L26S27E28I29K30) capable of
      providing the late assembly function. Alanine scanning studies of this L-domain
      sequence demonstrated that mutations of residues Y23, P24, and L26 abrogated the
      p9 late budding function; mutations of other residues in the p9 L domain did not
      substantially affect the level of EIAV Gag particle assembly. These data indicate
      that the L domain in EIAV p9 utilizes a YXXL motif which we hypothesize may
      interact with cellular proteins to facilitate virus particle budding from
      infected cells.

PMID- 9261375
TI  - Activation domain requirements for disruption of Epstein-Barr virus latency by
      ZEBRA.
AB  - Latent infection of B lymphocytes by Epstein-Barr virus (EBV) can be disrupted by
      expression of the EBV ZEBRA protein. ZEBRA, a transcriptional activator,
      initiates the EBV lytic cascade by activating viral gene expression. ZEBRA is
      also indispensable for viral replication and binds directly to the EBV lytic
      origin of replication. The studies described herein demonstrate that the
      activation domain. ZEBRA activation can be replaced by a heterologous acidic,
      proline-rich, or glutamine-rich activation domain. ZEBRA activation domain swap
      constructs retain ZEBRA's native abilities to activate specific EBV promoters, to
      disrupt EBV latency, and to stimulate replication at the EBV lytic origin.
      Additional work, employing sequential and internal deletions of ZEBRA's N
      terminal activation domain, indicates that its separate activities are not
      attributable to specific subdomains but are spread throughout its N terminus and
      therefore cannot be inactivated by deleting localized regions.

PMID- 9261376
TI  - A 437-base-pair deletion at the beginning of the latency-associated transcript
      promoter significantly reduced adrenergically induced herpes simplex virus type 1
      ocular reactivation in latently infected rabbits.
AB  - In this study we used a herpes simplex virus type 1 (HSV-1) deletion mutant to
      identify a segment of the genome necessary for epinephrine-induced reactivation
      in the rabbit eye model of herpetic recurrent disease. In HSV-1 latently infected
      neural tissue, the only abundant viral products are the latency-associated
      transcripts (LATs). At least one promoter of LAT has been identified, and
      mutations in the LAT domain have been used to investigate HSV-1 reactivation. We
      used an ocular rabbit model of epinephrine-induced HSV-1 reactivation to study
      the effects of deleting a 437-bp region beginning 796 bp upstream of the LAT CAP
      site. Specifically, the 437-bp deletion is located between genomic positions
      118006 and 118443 of the parent 17Syn+, and the construct is designated 17 delta
      S/N. This region also controls a portion of the genome encoding two transcripts
      (1.1 and 1.8 kb) from the LAT domain. A rescuant, 17 delta S/N-Res, was
      constructed from 17 delta S/N. Following ocular infection, all three viruses
      produced similar acute dendritic lesions in rabbits. Five weeks after infection,
      rabbits received transcorneal iontophoresis of epinephrine. The parent, 17Syn+,
      and the rescuant, 17 delta S/N-Res, underwent a high frequency of HSV-1 ocular
      reactivation as determined by recovery of infectious virus in the tear film.
      Rabbits infected with 17 delta S/N had a significantly lower frequency of ocular
      reactivation. Analysis of the trigeminal ganglia from all three groups of
      latently infected rabbits revealed (i) similar amounts of HSV DNA (genomic
      equivalents), (ii) accumulation of 2.0- and 1.45-kb LATs, and (iii) explant
      reactivation at the same high frequency. Therefore, these studies indicate that
      the 437-bp deleted region in 17 delta S/N is essential for epinephrine-induced
      reactivation and could implicate the 1.1- and 1.8-kb transcripts in the
      mechanisms controlling HSV-1 reactivation.

PMID- 9261377
TI  - The Epstein-Barr virus-induced Ca2+/calmodulin-dependent kinase type IV/Gr
      promotes a Ca(2+)-dependent switch from latency to viral replication.
AB  - The switch from latency to viral replication in Epstein-Barr virus (EBV)
      transformed human B cells is mediated by Zta, the protein product of immediate
      early EBV gene BZLF1. BZLF1 transcription is normally suppressed in EBV
      transformed B cells but can be induced in some cell lines upon ligation of
      surface immunoglobulin by mechanisms that include the activation of Ca(2+)
      dependent signaling pathways. The multifunctional Ca2+/calmodulin-dependent
      kinase type IV/Gr (CaMKIV/Gr) is normally absent in primary human B cells, but
      its expression is induced by the EBV oncoprotein LMP1 in the course of B-cell
      growth transformation by EBV. In this study, we demonstrate that activated
      CaMKIV/Gr induces transcription from the BZLF1 promoter and upregulates the
      expression of Zta in permissive cells. Transcriptional activation of the BZLF1
      promoter by CaMKIV/Gr is dependent on the CREB/AP1 binding element ZII and is
      greatly augmented by the Ca2+/calmodulin-dependent phosphatase calcineurin. These
      results outline a virus-regulated mechanism involving CaMKIV/Gr which promotes
      transition from latency to productive viral replication in response to Ca(2+)
      mobilizing extracellular signals.

PMID- 9261378
TI  - Characterization of the minute virus of mice P38 core promoter elements.
AB  - While the minute virus of mice (MVM) P4 promoter, which drives the viral
      nonstructural genes, is highly active in the absence of viral proteins, P38, the
      capsid gene promoter, is strictly dependent on the viral nonstructural protein
      NS1. Once fully transactivated, however, P38 mediates twice the steady-state
      level of expression achieved by P4. In this report, we address the discrepancy
      between the ability of P38 to mediate very high levels of activated transcription
      yet only low levels of basal expression, and we investigate the determinants that
      govern P38 basal expression. The isolated P38 core promoter elements (the P38 Sp1
      binding site and TATA element) are at least as transcriptionally competent as the
      analogous P4 promoter elements. Proximally positioning P4 enhancer factor-binding
      sequences (nucleotides [nt] 57 to 157) upstream of isolated P38 core
      transcription regulatory elements or upstream of a native, though abbreviated,
      P38 cassette (MVM nt 1938 to 2072) confers significant levels of expression to
      P38 in the absence of NS1, while the full left-end hairpin sequences (nt 1 to
      133) elevate basal P38 activity to levels equivalent to P4 basal levels. In the
      context of the complete viral genome, however, proximally positioned enhancer
      sequences are unable to confer significant levels of expression to P38,
      suggesting that low P38 basal levels are a consequence not only of a lack of
      proximal enhancer elements but also of additional positional regulatory
      constraints which can be overcome by NS1.

PMID- 9261379
TI  - Molecular characterization of the type-specific gamma-determinant located on the
      adenovirus fiber.
AB  - The fiber knob carries the type-specific gamma-antigen which can be demonstrated
      in hemagglutination inhibition tests. In order to characterize the gamma
      determinant we selected subgenus DI adenovirus serotypes 9 and 19 (Ad9 and Ad19)
      which exhibited 29 amino acid exchanges in the knob domain. Like all subgenus DI
      adenoviruses they showed a complete hemagglutination pattern with rat and human
      erythrocytes. We constructed a total of 14 chimeric Ad9/Ad19 and Ad19/Ad9 fiber
      proteins, which possessed fiber knobs with progressively exchanged Ad9 and Ad19
      amino acids. Furthermore, we created 39 fiber proteins with distinct amino acid
      exchanges in the knob regions by primer-directed mutagenesis. The proteins were
      expressed in Escherichia coli and tested in hemagglutination and hemagglutination
      inhibition tests. From our results we can conclude that the type-specific gamma
      determinant is not restricted to a distinct region on the adenovirus fiber knob
      but is composed of at least 17 amino acids. Most of the amino acids contributing
      to the Ad9 and Ad19 gamma-determinants are located on the fiber knob loops.

PMID- 9261380
TI  - Membrane binding of human immunodeficiency virus type 1 matrix protein in vivo
      supports a conformational myristyl switch mechanism.
AB  - The interaction of the human immunodeficiency virus (HIV) Gag protein with the
      plasma membrane of a cell is a critical event in the assembly of HIV particles.
      The matrix protein region (MA) of HIV type 1 (HIV-1) Pr55Gag has previously been
      demonstrated to confer membrane-binding properties on the precursor polyprotein.
      Both the myristic acid moiety and additional determinants within MA are essential
      for plasma membrane binding and subsequent particle formation. In this study, we
      demonstrated the myristylation-dependent membrane interaction of MA in an in vivo
      membrane-binding assay. When expressed within mammalian cells, MA was found both
      in association with cellular membranes and in a membrane-free form. In contrast,
      the intact precursor Pr55Gag molecule analyzed in an identical manner was found
      almost exclusively bound to membranes. Both membrane-bound and membrane-free
      forms of MA were myristylated and phosphorylated. Differential membrane binding
      was not due to the formation of multimers, as dimeric and trimeric forms of MA
      were also found in both membrane-bound and membrane-free fractions. To define the
      requirements for membrane binding of MA, we analyzed the membrane binding of a
      series of MA deletion mutants. Surprisingly, deletions within alpha-helical
      regions forming the globular head of MA led to a dramatic increase in overall
      membrane binding. The stability of the MA-membrane interaction was not affected
      by these deletions, and no deletion eliminated membrane binding of the molecule.
      These results establish that myristic acid is a primary determinant of the
      stability of the Gag protein-membrane interaction and provide support for the
      hypothesis that a significant proportion of HIV-1 MA molecules may adopt a
      conformation in which myristic acid is hidden and unavailable for membrane
      interaction.

PMID- 9261381
TI  - The amino-terminal fusion domain peptide of human immunodeficiency virus type 1
      gp41 inserts into the sodium dodecyl sulfate micelle primarily as a helix with a
      conserved glycine at the micelle-water interface.
AB  - A peptide based on the N-terminal fusion domain of gp41 of human immunodeficiency
      virus type 1 (HIV-1) and its tryptophan analog were synthesized to examine the
      secondary structure in the micellar environment. Nuclear magnetic resonance
      (NMR), circular dichroism and electron paramagnetic resonance experiments
      indicated that the gp41 fusion peptide inserted into the micelle primarily as a
      helix (59%), with substantial beta-structure (26.7%). Deep penetration of the
      peptide into the apolar hydrocarbon core was supported by the results of
      fluorescence experiments in which the tryptophan analog exhibited a blue shift of
      about 30 nm in the presence of a sodium dodecyl sulfate micelle, in 1,2
      dimyristoyl-rac-glycero-3-phosphocholine, and in 1,2-dipalmitoyl-sn-glycero-3
      phospho-L-serine vesicular solutions. The results of spin label-attenuated 1H
      resonance experiments show that the region C-terminal to G16, which contains a
      turn structure, exhibited substantial interaction with the micelle, suggesting
      that it lies on the surface of micelle. Molecular simulation based on data from
      NMR experiments revealed a flexible hinge at residues 15 and 16 (alanine and
      glycine, respectively) from the N terminus of the peptide located at the micelle
      solution interface. The highly conserved A15-G16 dipeptide may play a role in the
      function of fusion domain of HIV-1 envelope glycoprotein.

PMID- 9261382
TI  - A 451-nucleotide circular RNA from cherry with hammerhead ribozymes in its
      strands of both polarities.
AB  - The sequence of 451 nucleotides of a cherry small circular RNA (csc RNA1)
      associated with a cherry disease has been determined. Both csc RNA1 and its
      complementary strand can form hammerhead structures similar to those found
      previously in other plant and animal small RNAs. In the branched secondary
      structure of lowest free energy of csc RNA1, the sequences involved in the
      hammerhead structures, which comprise approximately one-fourth of this RNA, are
      found opposite each other, forming part of a rod-like segment. Plus- and minus
      strand full-length transcripts of csc RNA1 self-cleaved during transcription and
      after purification, as predicted by the hammerhead structures, which are stable
      and very probably act as single hammerhead structures. The minus-strand
      hammerhead structure of csc RNA1 is exceptional in having a central loop with
      only 11 conserved nucleotides, a situation previously observed in only one other
      natural hammerhead structure. Both hammerhead structures of csc RNA1 are also
      peculiar in having an A instead of a C preceding the self-cleavage sites. The in
      vivo concentration of the plus strand of csc RNA1 is only slightly higher than
      that of its complementary strand, and significant fractions of both strands are
      extracted from the tissue in the form of a complex. csc RNA1 has sequence
      similarities to viroids and especially to some viroid-like satellite RNAs; they
      also share some characteristics of their corresponding hammerhead structures with
      these satellite RNAs. These observations, together with the association in
      symptomatic tissue of csc RNA1 with a set of presumably viral double-stranded
      RNAs, suggest that csc RNA1 is a new viroid-like satellite RNA.

PMID- 9261383
TI  - Epstein-Barr virus nuclear protein LP stimulates EBNA-2 acidic domain-mediated
      transcriptional activation.
AB  - Epstein-Barr virus (EBV) nuclear proteins EBNA-LP and EBNA-2 are the first two
      proteins expressed in latent infection of primary B lymphocytes. EBNA-2 is
      essential for lymphocyte transformation, and EBNA-LP is at least critical. While
      EBNA-2 activates specific viral and cellular promoters, EBNA-LP's role has been
      obscure. We now show that EBNA-LP stimulates EBNA-2 activation of the LMP1
      promoter and of the LMP1/LMP2B bidirectional transcriptional regulatory element.
      EBNA-LP alone has only a negative effect. EBNA-LP also stimulates EBNA-2
      activation of a multimerized regulatory element from the BamC EBNA promoter.
      Since both viral regulatory elements can bind the EBNA-2-associated cell protein
      RBPJ kappa, consensus RBPJ kappa binding sites were positioned upstream of the
      herpes simplex virus type 1 thymidine kinase promoter and were found to be
      sufficient for EBNA-LP and EBNA-2 coactivation. EBNA-LP strongly stimulated
      activation of an adenovirus E1b promoter with upstream Gal4 binding sites by a
      Gal4 DNA binding domain/ EBNA-2 acidic domain fusion protein, indicating that
      EBNA-LP coactivation requires only the EBNA-2 acidic domain to be localized near
      a promoter. The EBNA-LP stimulatory activity resides in the amino-terminal 66
      amino-acid repeat domain. The carboxyl-terminal unique 45 amino acids appear to
      regulate EBNA-LP's effects. The first 11 amino acids of the 45 have a strong
      negative effect, while the last 10 are critical for the ability of the last 34 to
      relieve the negative effect. These results indicate that EBNA-LP's critical role
      in EBV-mediated cell growth transformation is in stimulating (and probably
      regulating) EBNA-2-mediated transcriptional activation.

PMID- 9261384
TI  - Epstein-Barr virus leader protein enhances EBNA-2-mediated transactivation of
      latent membrane protein 1 expression: a role for the W1W2 repeat domain.
AB  - The Epstein-Barr virus (EBV)-encoded leader protein EBNA-LP is made up of several
      66-amino-acid repeats (the W1W2 domains) linked to a unique 45-amino-acid C
      terminal sequence (the Y1Y2 domain). This protein is highly expressed along with
      a second nuclear antigen, EBNA-2, during the initial stages of virus-induced B
      cell transformation. While EBNA-2's essential role in transformation as a
      transcriptional activatory is well documented, very little is known about EBNA-LP
      function except that recombinant viruses lacking the EBNA-LP Y1Y2 exons show
      reduced, but still detectable, transforming ability. This was taken as evidence
      that EBNA-LP plays an auxiliary role but is not essential for transformation. A
      recent study showed that EBNA-LP could cooperate with EBNA-2 in activating cyclin
      D2 transcription in resting B cells (A.J. Sinclair, L Palmero, G. Peters, and
      P.J. Farrell, EMBO J. 13:3321-3328, 1994). Here we report that EBNA-LP can also
      cooperate with EBNA-2 in up-regulating expression of the major EBV effector
      protein of B-cell transformation, latent membrane protein 1 (LMP1). In transient
      transfection assays, EBNA-LP enhanced the level of EBNA-2-induced LMP1 expression
      by 5- to 10-fold in one Latency I Burkitt's lymphoma cell line, Eli-BL, and was
      absolutely required, along with EBNA-2, to induce LMP1 in a second line, Akata
      BL. These changes in LMP1 protein expression appeared to be reflected at the
      transcriptional level. A study of EBNA-LP mutants showed that this cooperative
      function mapped to the W1W2 repeat domain rather than to Y1Y2. Because a Y1Y2
      deleted form of EBNA-LP may therefore retain some aspects of wild-type function,
      the original data from virus recombinants leave open the possibility that EBNA-LP
      is actually an essential transforming gene.

PMID- 9261385
TI  - Adenovirus type 12 early region 1B 54K protein significantly extends the life
      span of normal mammalian cells in culture.
AB  - The life span of normal human cells in culture is extended by two to four total
      life spans following retrovirus-mediated transfer of the adenovirus type 12 E1B
      54,000-molecular-weight protein (54K protein). This extension of the in vitro
      growth potential was accomplished without any of the obvious changes in
      morphology or growth properties that are usually associated with viral
      transformation. These 54K+ cells escape the normal senescence checkpoint (M1) and
      show a very extended secondary growth phase. The 54K+ human cells eventually
      enter crisis (M2), which does not appear to be due to either telomere attrition
      or the activation of the senescence-associated proteins p21SdilCipIWaf1 and
      p16INK4A. Even in the absence of telomerase activity, high-molecular-weight
      heterogeneous telomeres are produced and maintained in both 54K+ adult dermal
      fibroblasts and embryo kidney cells, indicating that the 54K protein may
      interfere with the normal metabolism of telomeric structures during cell
      division. These findings are discussed with reference to the known ability of the
      54K protein to influence p53 function.

PMID- 9261386
TI  - Highly efficient and sustained gene transfer in adult neurons with a lentivirus
      vector.
AB  - The identification of monogenic and complex genes responsible for neurological
      disorders requires new approaches for delivering therapeutic protein genes to
      significant numbers of cells in the central nervous system. A lentivirus-based
      vector capable of infecting dividing and quiescent cells was investigated in vivo
      by injecting highly concentrated viral vector stock into the striatum and
      hippocampus of adult rats. Control brains were injected with a Moloney murine
      leukemia virus, adenovirus, or adeno-associated virus vector. The volumes of the
      areas containing transduced cells and the transduced-cell densities were
      stereologically determined to provide a basis for comparison among different
      viral vectors and variants of the viral vector stocks. The efficiency of
      infection by the lentivirus vector was improved by deoxynucleoside triphosphate
      pretreatment of the vector and was reduced following mutation of integrase and
      the Vpr-matrix protein complex involved in the nuclear translocation of the
      preintegration complex. The lentivirus vector system was able to efficiently and
      stably infect quiescent cells in the primary injection site with transgene
      expression for over 6 months. Triple labeling showed that 88.7% of striatal cells
      transduced by the lentivirus vector were terminally differentiated neurons.

PMID- 9261388
TI  - Drug resistance during indinavir therapy is caused by mutations in the protease
      gene and in its Gag substrate cleavage sites.
AB  - Two different responses to the therapy were observed in a group of patients
      receiving the protease inhibitor indinavir. In one, suppression of virus
      replication occurred and has persisted for 90 weeks (bDNA, < 500 human
      immunodeficiency virus type 1 [HIV-1] RNA copies/ml). In the second group, a
      rebound in virus levels in plasma followed the initial sharp decline observed at
      the start of therapy. This was associated with the emergence of drug-resistant
      variants. Sequence analysis of the protease gene during the course of therapy
      revealed that in this second group there was a sequential acquisition of protease
      mutations at amino acids 46, 82, 54, 71, 89, and 90. In the six patients in this
      group, there was also an identical mutation in the gag p7/p1 gag protease
      cleavage site. In three of the patients, this change was seen as early as 6 to 10
      weeks after the start of therapy. In one patient, a second mutation occurred at
      the gag p1/p6 cleavage site, but it appeared 18 weeks after the time of
      appearance of the p7/p1 mutation. Recombinant HIV-1 variants containing two or
      three mutations in the protease gene were constructed either with mutations at
      the p7/p1 cleavage site or with wild-type (WT) gag sequences. When recombinant
      HIV-1-containing protease mutations at 46 and 82 was grown in MT2 cells, there
      was a 68% reduction in its rate of replication compared to the WT virus.
      Introduction of an additional mutation at the gag p7/p1 protease cleavage site
      compensated for the partially defective protease gene. Similarly, rates of
      replication of viruses with mutations M46L/I, I54V, and V82A in protease were
      enhanced both in the presence and in the absence of Indinavir when combined with
      mutations in the gag p7/p1 and the gag p1/p6 cleavage sites. Optimal rates of
      virus replication require protease cleavage of precursor polyproteins. A mutation
      in the cleavage site that enhanced the availability of a protein that was rate
      limiting for virus maturation would confer on that virus a significant growth
      advantage and may explain the uniform emergence of viruses with alterations at
      the p7/p1 cleavage site. This is the first report of the emergence of mutations
      in the gag p7/p1 protease cleavage sites in patients receiving protease therapy
      and identifies this change as an important determinant of HIV-1 resistance to
      protease inhibitors in patient populations.

PMID- 9261389
TI  - Human immunodeficiency virus type 1 infection of mature CD3hiCD8+ thymocytes.
AB  - Although CD4+ cells are the primary targets of human immunodeficiency virus type
      1 (HIV-1) infection, earlier reports have suggested that intrathymic infection of
      CD8+ cells may occur. However, it was unclear whether HIV-1-infected CD8+
      thymocytes were truly mature single-positive (SP) cells. In the present study,
      SCID mice implanted with human fetal thymus and liver tissues (SCID-hu mice) were
      infected with three primary isolates of HIV-1 and infected thymocytes were
      analyzed to assess maturational status. After intra-implant or intraperitoneal
      injection with HIV-1, thymocytes were sorted by three-color flow cytometric
      analysis into mature populations of CD3hiCD4+ and CD3hiCD8+ SP cells of > 99%
      purity (< 0.3% CD4-containing cells in the CD8+ population). The presence of HIV
      1 provirus in the sorted thymocyte populations was determined by quantitative
      PCR. A fraction of mature CD3hiCD8+ thymocytes contained HIV-1 proviral DNA, and
      evidence of viral mRNA transcription in these cells was demonstrated by in situ
      hybridization. In contrast, when uninfected CD3hiCD8+ thymocytes were cocultured
      with HIV-1-infected CD4+ thymocytes, no evidence of productive HIV-1 infection
      was detected. Thus, HIV-1 infection of CD8+ thymocytes in the SCID-hu mouse does
      not occur by direct contact with the virus. Rather, cell surface CD4 is required;
      therefore, precursor cells are the likely primary target of HIV-1 infection in
      the thymus. During ontogeny, some of these infected cells continue their
      differentiation into mature CD8+ SP thymocytes that contain proviral DNA and
      express viral RNA.

PMID- 9261387
TI  - Ultrastructure of Kunjin virus-infected cells: colocalization of NS1 and NS3 with
      double-stranded RNA, and of NS2B with NS3, in virus-induced membrane structures.
AB  - The subcellular location of the nonstructural proteins NS1, NS2B, and NS3 in Vero
      cells infected with the flavivirus Kunjin was investigated using indirect
      immunofluorescence and cryoimmunoelectron microscopy with monospecific
      antibodies. Comparisons were also made by dual immunolabelling using antibodies
      to double-stranded RNA (dsRNA), the putative template in the flavivirus
      replication complex. At 8 h postinfection, the immunofluorescent patterns showed
      NS1, NS2B, NS3, and dsRNA located in a perinuclear rim with extensions into the
      peripheral cytoplasm. By 16 h, at the end of the latent period, all patterns had
      changed to some discrete perinuclear foci associated with a thick cytoplasmic
      reticulum. By 24 h, this localization in perinuclear foci was more apparent and
      some foci were dual labelled with antibodies to dsRNA. In immuno-gold-labelled
      cryosections of infected cells at 24 h, all antibodies were associated with
      clusters of induced membrane structures in the perinuclear region. Two important
      and novel observations were made. First, one set of induced membranes comprised
      vesicle packets of smooth membranes dual labelled with anti-dsRNA and anti-NS1 or
      anti-NS3 antibodies. Second, adjacent masses of paracrystalline arrays or of
      convoluted smooth membranes, which appeared to be structurally related, were
      strongly labelled only with anti-NS2B and anti-NS3 antibodies. Paired membranes
      similar in appearance to the rough endoplasmic reticulum were also labelled, but
      less strongly, with antibodies to the three nonstructural proteins. Other paired
      membranes adjacent to the structures discussed above enclosed accumulated virus
      particles but were not labelled with any of the four antibodies. The collection
      of induced membranes may represent virus factories in which translation, RNA
      synthesis, and virus assembly occur.

PMID- 9261390
TI  - Activation of STAT transcription factors by herpesvirus Saimiri Tip-484 requires
      p56lck.
AB  - Signal transducers and activators of transcription (STATs) relay signals from
      activated cell surface receptors directly to the nucleus. Previously, a protein
      required for T-cell transformation by the DNA tumor virus herpesvirus saimiri
      (HVS) and designated tyrosine kinase interacting protein (Tip-484) was shown to
      interact with and dramatically upregulate the activity of p56lck. p56lck is a
      nonreceptor tyrosine kinase that is essential for signaling by the T-cell
      receptor and also interacts with the CD4, CD8, and interleukin-2 receptors. The
      present data show activation of STAT1 and -3 by Tip-484. STAT1 and -3 were also
      found to complex with glutathione S-transferase-Tip-484 only in the presence of
      p56lck, and STAT3 was shown to be phosphorylated by the Tip-484-p56lck
      multiprotein complex in vitro. Infection of T cells with HVS or expression of
      recombinant Tip-484 significantly increased the DNA-binding activity of the STAT1
      and STAT3 transcription factors in nuclear extracts and also increased the
      phosphorylation of STAT3 in vivo. This is the first report of STAT activation by
      a DNA tumor virus protein. Moreover, these studies demonstrate that p56lck is
      required for STAT activation by Tip-484.

PMID- 9261391
TI  - Binding of SP1 to the immediate-early protein-responsive element of the human
      cytomegalovirus DNA polymerase promoter.
AB  - Human cytomegalovirus (HCMV), a member of the herpesvirus family of DNA viruses,
      encodes two major immediate-early (IE) transcription factors, IE72 and IE86, that
      are important for regulated expression of the viral genome. The purpose of this
      study was to identify the host cellular components required for regulation of the
      HCMV DNA polymerase promoter (UL54) by HCMV IE proteins. Extensive mutagenesis
      defined a DNA element located between -54 and -43 relative to the transcription
      start site that was required for both basal transcriptional activity and
      transactivation by viral IE proteins. A single copy of the UL54 -54/-43 sequence
      enhanced the responsiveness of a heterologous minimal promoter to HCMV IE
      proteins. Fractionation of extracts prepared from uninfected cells led to the
      isolation of two cellular proteins with apparent molecular masses of 95 and 105
      kDa that bound specifically to the UL54 -54/-43 element. Biochemical and
      immunochemical analyses identified this protein as the transcription factor SP1.
      Although initial inspection of the UL54 -54/-43 sequence did not predict an SP1
      binding site, subsequent analyses indicated that it is indeed a nonconsensus GC
      box. We propose that SP1 is required to direct basal levels of promoter activity
      and that SP1-regulated transcription complexes allow the entry of HCMV IE
      proteins into the transcription cycle.

PMID- 9261392
TI  - Glycoprotein Erns of pestiviruses induces apoptosis in lymphocytes of several
      species.
AB  - Classical swine fever virus and bovine virus diarrhea virus are members of the
      genus pestivirus, which belongs to the family of the Flaviviridae. Recently,
      envelope glycoprotein Erns was identified as an RNase. RNases can express
      different biological actions. They have been shown to be neurotoxic,
      antihelminthic, and immunosuppressive. We studied the immunosuppressive
      properties of Erns in vitro. The glycoprotein totally inhibited concanavalin A
      induced proliferation of porcine, bovine, ovine, and human lymphocytes. We then
      studied the direct cytotoxic effects of Erns on lymphocytes and epithelial cells
      in protein synthesis assays. Erns strongly inhibited the protein synthesis of
      lymphocytes of different species, without cell membrane damage. This suggested an
      apoptotic process, and indeed apoptosis of lymphocytes was detected after
      incubation with Erns. Pestivirus infections are characterized by leukopenia and
      immunosuppression. Our results suggest that Erns plays an important role in the
      pathogenesis of pestiviruses.

PMID- 9261393
TI  - Repeated emergence of epidemic/epizootic Venezuelan equine encephalitis from a
      single genotype of enzootic subtype ID virus.
AB  - Venezuelan equine encephalitis (VEE) epidemics and equine epizootics occurred
      periodically in the Americas from the 1920s until the early 1970s, when the
      causative viruses, subtypes IAB and IC, were postulated to have become extinct.
      Recent outbreaks in Columbia and Venezuela have renewed interest in the source of
      epidemic/epizootic viruses and their mechanism of interepizootic maintenance. We
      performed phylogenetic analyses of VEE virus isolates spanning the entire
      temporal and geographic range of strains available, using 857-nucleotide reverse
      transcription-PCR products including the E3 and E2 genes. Analyses indicated that
      epidemic/epizootic viruses are closely related to four distinct, enzootic subtype
      ID-like lineages. One of these lineages, which occurs in Columbia, Peru, and
      Venezuela, also included all of the epidemic/epizootic isolates; the remaining
      three ID-like lineages, which occur in Panama, Peru, Florida, coastal Ecuador,
      and southwestern Columbia, were apparently not associated with epizootic VEE
      emergence. Within the Columbia/Peru/Venezuela lineage, three distinct
      monophyletic groups of epidemic/epizootic viruses were delineated, indicating
      that VEE emergence has occurred independently at least three times (convergent
      evolution). Representative, complete E2 amino acid sequences were compared to
      identify potential determinants of equine virulence and epizootic emergence.
      Amino acids implicated previously in laboratory mouse attenuation generally did
      not vary among the natural isolates that we examined, indicating that they
      probably are not involved in equine virulence changes associated with VEE
      emergence. Most informative amino acids correlated with phylogenetic
      relationships rather than phenotypic characteristics, suggesting that VEE
      emergence has resulted from several distinct combinations of mutations that
      generate viruses with similar antigenic and equine virulence phenotypes.

PMID- 9261394
TI  - Neuraminidase hemadsorption activity, conserved in avian influenza A viruses,
      does not influence viral replication in ducks.
AB  - The N1 and N9 neuraminidase (NA) subtypes of influenza A viruses exhibit
      significant hemadsorption activity that localizes to a site distinct from that of
      the enzymatic active site. To determine the conservation of hemadsorption
      activity among different NAs, we have examined most of the NA subtypes from
      avian, swine, equine, and human virus isolates. All subtypes of avian virus NAs
      examined and one equine virus N8 NA possessed high levels of hemadsorption
      activity. A swine virus N1 NA exhibited only weak hemadsorption activity, while
      in human virus N1 and N2 NAs, the activity was detected at a much lower level
      than in avian virus NAs. NAs which possessed hemadsorption activity for chicken
      erythrocytes (RBCs) were similarly able to adsorb human RBCs. However, none of
      the hemadsorption-positive NAs could bind equine, swine, or bovine RBCs,
      suggesting that RBCs from these species lack molecules, recognized by the NA
      hemadsorption site, present on human and chicken RBCs. Mutagenesis of the
      putative hemadsorption site of A/duck/Hong Kong/7/75 N2 NA abolished the high
      level of hemadsorption activity exhibited by the wild-type protein but also
      resulted in a 50% reduction of the NA enzymatic activity. A transfectant virus,
      generated by reverse genetics, containing this mutated NA replicated 10-fold less
      efficiently in chicken embryo fibroblast cultures than did a transfectant virus
      expressing the wild-type NA. However, both viruses replicated equally well in
      Peking ducks. Although conservation of NA hemadsorption activity among avian
      virus NAs suggests the maintenance of a required function of NA, loss of the
      activity does not preclude the replication of the virus in an avian host.

PMID- 9261395
TI  - The latency-associated promoter of herpes simplex virus type 1 requires a region
      downstream of the transcription start site for long-term expression during
      latency.
AB  - The latency-associated transcript (LAT) promoter of herpes simplex virus type 1
      (HSV-1) is unique among the many promoters on the viral genome in that it remains
      active during the latent state. We have previously shown that a DNA fragment
      comprising the LAT promoter element through the cap site, when moved from the LAT
      locus to the glycoprotein C gene, is capable of only short-term expression. These
      and other data suggested that an HSV DNA element from the repeat region, not
      included in the LAT promoter itself, might be needed to preserve long-term
      expression. Based on a number of recombinant viruses, we narrowed our search for
      this putative element to a region 3' of the LAT transcription start site. In the
      present study, we have shown that a 1.1-kb DNA fragment containing the putative
      long-term expression element (LTE) is able to restore latent-phase gene
      expression to the LAT promoter. The element appeared to function best when it was
      placed in its natural location, which is 3' of the LAT promoter; however, partial
      function was obtained when the LTE was inserted upstream of the LAT promoter in
      the reverse direction. These data indicate that the LAT promoter region is more
      complex than originally anticipated and that in addition to requiring both core
      promoter and neuronal transcription factor binding sites, the promoter requires a
      specific region of DNA to prevent its shutoff during a latent infection.

PMID- 9261396
TI  - Specific interaction of polypyrimidine tract-binding protein with the extreme 3'
      terminal structure of the hepatitis C virus genome, the 3'X.
AB  - We previously identified a highly conserved 98-nucleotide (nt) sequence, the 3'X,
      as the extreme 3'-terminal structure of the hepatitis C virus (HCV) genome (T.
      Tanaka, N. Kato, M.-J. Cho, and K. Shimotohno, Biochem. Biophys. Res. Commun.
      215:744-749, 1995). Since the 3' end of positive-strand viral RNA is the
      initiation site of RNA replication, the 3'X should contribute to HCV negative
      strand RNA synthesis. Cellular factors may also be involved in this replication
      mechanism, since several cellular proteins have been shown to interact with the
      3'-end regions of other viral genomes. In this study, we found that both 38- and
      57-kDa proteins in the human hepatocyte line PH5CH bound specifically to the 3'
      end structure of HCV positive-strand RNA by a UV-induced cross-linking assay. The
      57-kDa protein (p57), which had higher affinities to RNA probes, recognized a 26
      nt sequence including the 5'-terminal 19 nt of the 3'X and 7 flanking nt,
      designated the transitional region. This sequence contains pyrimidine-rich motifs
      and shows similarity to the consensus binding sequence of the polypyrimidine
      tract-binding protein (PTB), which has been implicated in alternative pre-mRNA
      splicing and cap-independent translation. We found that this 3'X-binding p57 is
      identical to PTB. The 3'X-binding p57 was immunoprecipitated by anti-PTB
      antibody, and recombinant PTB bound to the 3'X RNA. In addition, p57 bound solely
      to the 3'-end region of positive-strand RNA, not to this region of negative
      strand RNA. We suggest that 3'X-PTB interaction is involved in the specific
      initiation of HCV genome replication.

PMID- 9261397
TI  - Characterization of the genome of feline foamy virus and its proteins shows
      distinct features different from those of primate spumaviruses.
AB  - The genome of the feline foamy virus (FeFV) isolate FUV was characterized by
      molecular cloning and nucleotide sequence analysis of subgenomic proviral DNA.
      The overall genetic organization of FeFV and protein sequence comparisons of
      different FeFV genes with their counterparts from other known foamy viruses
      confirm that FeFV is a complex foamy virus. However, significant differences
      exist when FeFV is compared with primate foamy viruses. The FeFV Gag protein is
      smaller than that of the primate spumaviruses, mainly due to additional MA/CA
      sequences characteristic of the primate viruses only. Gag protein sequence motifs
      of the NC domain of primate foamy viruses assumed to be involved in genome
      encapsidation are not conserved in FeFV. FeFV Gag and Pol proteins were detected
      with monospecific antisera directed against Gag and Pol domains of the human
      foamy virus and with antisera from naturally infected cats. Proteolytic
      processing of the FeFV Gag precursor was incomplete, whereas more efficient
      proteolytic cleavage of the pre125Pro-Pol protein was observed. The active center
      of the FeFV protease contains a Gln that replaces an invariant Gly residue at
      this position in other retroviral proteases. Functional studies on FeFV gene
      expression directed by the promoter of the long terminal repeat showed that FeFV
      gene expression was strongly activated by the Bell/Tas transactivator protein.
      The FeFV Bell/Tas transactivator is about one-third smaller than its counterpart
      of primate spumaviruses. This difference is also reflected by a limited sequence
      similarity and only a moderate conservation of structural motifs of the different
      foamy virus transactivators analyzed.

PMID- 9261398
TI  - Human immunodeficiency virus types 1 and 2 and simian immunodeficiency virus Nef
      use distinct but overlapping target sites for downregulation of cell surface CD4.
AB  - Although the Nef proteins encoded by human immunodeficiency virus type 1 (HIV-1)
      and simian immuno-deficiency virus (SIV) are known to induce the efficient
      internalization and degradation of cell surface CD4, it remains unclear whether
      this process involves a direct interaction between Nef and CD4. Here, we report
      that CD4 downregulation by HIV-1 and SIV Nef requires distinct but overlapping
      target sites within the CD4 intracytoplasmic domain. In particular, mutation of a
      glutamic acid residue located at CD4 residue 405 or of arginine and methionine
      residues located, respectively, at residue 406 and 407 results in a mutant CD4
      protein that is efficiently downregulated by HIV-1 Nef but refractory to
      downregulation by SIV Nef. However, both HIV-1 and SIV Nef require an isoleucine
      located at residue 410 and the dileucine motif found at CD4 residues 413 and 414.
      CD4 downregulation induced by the Nef protein encoded by HIV-2 is shown to
      require a CD4 target sequence that is similar to, but distinct from, that
      observed with SIV Nef. These data explain the previous finding that the murine
      CD4 protein, which has an alanine at residue 405, is refractory to downregulation
      by SIV, but not HIV-1, Nef (J. L. Foster, S.J. Anderson, A. L. B. Frazier, and J.
      V. Garcia, Virology 201:373-379, 1994). In addition, these observations provide
      strong genetic support for the hypothesis that the Nef-mediated downregulation of
      cell surface CD4 requires a direct Nef-CD4 interaction.

PMID- 9261399
TI  - Functional and structural analysis of the sialic acid-binding domain of
      rotaviruses.
AB  - The infectivity of most animal rotaviruses is dependent on the interaction of the
      virus spike protein VP4 with a sialic acid (SA)-containing cell receptor, and the
      SA-binding domain of this protein has been mapped between amino acids 93 and 208
      of its trypsin cleavage fragment VP8. To identify which residues in this region
      are essential for the SA-binding activity, we performed alanine mutagenesis of
      the rotavirus RRV VP8 expressed in bacteria as a fusion polypeptide with
      glutathione S-transferase. Tyrosines were primarily targeted since tyrosine has
      been involved in the interaction of other viral hemagglutinins with SA. Of the 15
      substitutions carried out, 10 abolished the SA-dependent hemagglutination
      activity of the protein, as well as its ability to bind to glycophorin A in a
      solid-phase assay. However, only alanine substitutions for tyrosines 155 and 188
      and for serine 190 did not affect the overall conformation of the protein, as
      judged by their interaction with a panel of conformationally sensitive
      neutralizing VP8 monoclonal antibodies (MAbs). These findings suggest that these
      three amino acids play an essential role in the SA-binding activity of the
      protein, presumably by interacting directly with the SA molecule. The predicted
      secondary structure of VP8 suggests that it is organized as 11 beta-strands
      separated by loops; in this model, Tyr-155 maps to loop 7 while Tyr-188 and Ser
      190 map to loop 9. The close proximity of these two loops is also supported by
      previous results from competition experiments with neutralizing MAbs directed at
      RRV VP8.

PMID- 9261400
TI  - A novel type of defective viral genome suggests a unique strategy to establish
      and maintain persistent lymphocytic choriomeningitis virus infections.
AB  - Defective interfering RNAs have long been thought to be a causal factor of
      persistent RNA virus infections. Here we describe a novel type of defective
      genome of lymphocytic choriomeningitis virus and the unique mechanism by which
      these RNAs appear to contribute to the establishment and maintenance of
      persistent infection. The defective genomes have short deletions in the
      untranslated regions at their termini and additional nontemplated terminal
      nucleotides. This and previous work from our laboratory suggested that the RNAs
      were competent for replication but not for transcription. From experiments using
      a technique to unambiguously determine the sequences of individual RNA termini,
      it appears that some truncated RNAs can be repaired. The data suggest that the
      loss or gain of nucleotides from the RNA termini during the course of infection
      is the mechanism for establishing and maintaining persistence.

PMID- 9261401
TI  - Effects of nucleocapsid mutations on human immunodeficiency virus assembly and
      RNA encapsidation.
AB  - The human immunodeficiency virus (HIV) Pr55Gag precursor proteins direct virus
      particle assembly. While Gag-Gag protein interactions which affect HIV assembly
      occur in the capsid (CA) domain of Pr55Gag, the nucleocapsid (NC) domain, which
      functions in viral RNA encapsidation, also appears to participate in virus
      assembly. In order to dissect the roles of the NC domain and the p6 domain, the C
      terminal Gag protein domain, we examined the effects of NC and p6 mutations on
      virus assembly and RNA encapsidation. In our experimental system, the p6 domain
      did not appear to affect virus release efficiency but p6 deletions and
      truncations reduced the specificity of genomic HIV-1 RNA encapsidation. Mutations
      in the nucleocapsid region reduced particle release, especially when the p2
      interdomain peptide or the amino-terminal portion of the NC region was mutated,
      and NC mutations also reduced both the specificity and the efficiency of HIV-1
      RNA encapsidation. These results implicated a linkage between RNA encapsidation
      and virus particle assembly or release. However, we found that the mutant
      ApoMTRB, in which the nucleocapsid and p6 domains of HIV-1 Pr55Gag were replaced
      with the Bacillus subtilis MtrB protein domain, released particles efficiently
      but packaged no detectable RNA. These results suggest that, for the purposes of
      virus-like particle assembly and release, NC can be replaced by a protein that
      does not appear to encapsidate RNA.

PMID- 9261402
TI  - The herpes simplex virus type 1 immediate-early protein ICP0 is necessary for the
      efficient establishment of latent infection.
AB  - The immediate-early protein ICP0 of herpes simplex virus type 1 (HSV-1) is not
      essential for viral replication. However, ICP0 is important for efficient viral
      replication during the productive infection and for reactivation of latent HSV-1
      in vivo. The in vitro model of HSV-1 latency in dorsal root ganglia neurons was
      used to examine the role of ICP0 in the individual steps that could lead to the
      appearance of a decreased reactivation phenotype of ICP0 mutant viruses. After
      establishment of latent infections in the neuronal cultures, induction of
      reactivation by nerve growth factor (NGF) deprivation resulted in the production
      of infectious virus with delayed kinetics and a burst size that was significantly
      decreased for the ICP0 mutants compared with wild-type HSV-1. The efficiency of
      establishment of latency with the ICP0 mutants was similarly decreased at least
      10-fold, as measured by three criteria: (i) the percentage of neurons expressing
      the major latency-associated transcript during the latent infection, (ii) the
      amount of viral DNA detected in the neuronal cultures, and (iii) the percentage
      of neurons expressing ICP4 immunoreactivity after the induction of reactivation.
      The most striking finding was that ICP0 supplied by an adenovirus vector
      significantly restored the ability of an ICP0 mutant to establish latency and
      reactivation. These results strongly indicate a critical role for ICP0 in the
      establishment of the latent HSV-1 infection in the in vitro neuronal model.

PMID- 9261403
TI  - Analysis of bovine herpesvirus 1 transcripts during a primary infection of
      trigeminal ganglia of cattle.
AB  - During an infection of nonneuronal cells, bovine herpesvirus 1 (BHV-1) gene
      expression proceeds in a well-defined cascade. Products of immediate-early (IE)
      genes are expressed first, and they activate expression of early (E) and late (L)
      genes. Although the same cascade is assumed to occur during an infection of
      neurons in trigeminal ganglia (TG) of cattle, no experimental data is available
      to support this hypothesis. Consequently, we analyzed BHV-1 gene expression in
      bovine TG at 1, 2, 4, 7, and 15 days postinfection (dpi). Infectious virus was
      detected in ocular swabs from 1 to 7 dpi but not 15 dpi. By reverse transcription
      (RT)-PCR, IE (bICP4), E (thymidine kinase, ribonucleotide reductase [RR]), L
      (glycoprotein C, and alpha trans-inducing factor), and dual-kinetic (bICP0 and
      bICP22) transcripts were analyzed. When cDNA synthesis was primed with random
      hexamers, IE and E transcripts were detected at the same time. However, full
      length and poly(A)+ (FL&P) RR or bICP22 RNAs were detected before FL&P IE RNAs.
      Furthermore, FL&P IE transcripts were not detected until viral DNA increased in
      TG. IE transcripts were detected before E or L RNAs when rabbit kidney cells were
      infected with a low multiplicity of infection and the same RT-PCR detection
      method was used. These studies suggested that expression of full-length and
      polyadenylated IE transcripts in trigeminal ganglia was not efficient compared to
      that of RR and bICP22 transcripts.

PMID- 9261404
TI  - The genes encoding the peripheral cannabinoid receptor and alpha-L-fucosidase are
      located near a newly identified common virus integration site, Evi11.
AB  - A new common region of virus integration, Evi11, has been identified in two
      retrovirally induced murine myeloid leukemia cell lines, NFS107 and NFS78. By
      interspecific backcross analysis, it was shown that Evi11 is located at the
      distal end of mouse chromosome 4, in a region that shows homology with human
      1p36. The genes encoding the peripheral cannabinoid receptor (Cnr2) and alpha-L
      fucosidase (Fuca1) were identified near the integration site by using a novel
      exon trapping system. Cnr2 is suggested to be the target gene for viral
      interference in Evi11, since proviruses are integrated in the first intron of
      Cnr2 and retroviral integrations alter mRNA expression of Cnr2 in NFS107 and
      NFS78. In addition, proviral integrations were demonstrated within the 3'
      untranslated region of Cnr2 in five independent newly derived CasBrM-MuLV (mouse
      murine leukemia virus) tumors, CSL13, CSL14, CSL16, CSL27, and CSL97. The Cnr2
      gene encodes a seven-transmembrane G-protein-coupled receptor which is normally
      expressed in hematopoietic tissues. Our data suggest that the peripheral
      cannabinoid receptor gene might be involved in leukemogenesis as a result of
      aberrant expression of Cnr2 due to retroviral integration in Evi11.

PMID- 9261405
TI  - Bovine papillomavirus type 1 DNA replication: the transcriptional activator E2
      acts in vitro as a specificity factor.
AB  - We previously devised cell-free conditions supporting efficient replication of
      bovine papillomavirus type 1 (BPV1) DNA (C. Bonne-Andrea, S. Santucci, and P.
      Clertant, J. Virol. 69:3201-3205, 1995): the use of highly active preparations of
      viral initiator protein E1, together with extract from a particular cell source,
      allowed the synthesis of complete DNA circles through successive rounds of
      replication; this occurred in the absence of the viral transcriptional activator
      E2, required in vivo for the replication of viral genomes. We now report that
      adding E2 to cell-free assays produced only slight effects both on the yield of
      E1-dependent DNA synthesis and on the quality of newly made DNA molecules when a
      template carrying a wild-type BPV1 replication origin (ori) was used. The
      performance of mouse cell extracts, unable to sustain efficient BPV1 DNA
      replication in the presence of E1 only, was likewise not improved by the addition
      of E2. In a proper in vitro environment, E1 is thus fully capable of efficiently
      initiating viral DNA synthesis by itself, an activity which is not enhanced by
      interaction with E2. An important effect, however, was detected: E2 totally
      suppressed the nonspecific replication of ori-defective DNA templates, otherwise
      observed in high E1 concentrations. We examined the requirements for building a
      minimal DNA sequence behaving in vitro as a specific ori sequence under stringent
      recognition conditions, i.e., in the presence of both E1 and E2. Only two
      elements, the 18-bp E1 binding palindrome and an AT-rich sequence, were required
      in cis to allow specific cell-free DNA replication; there seemed to be no need
      for an E2 binding site to ensure discrimination between specific ori templates
      and other DNA molecules, even in the presence of E2. This suggests that during
      the initiation of BPV1 DNA replication, at least in vitro, E2 acts as a
      specificity factor restricting the action of E1 to a defined ori sequence; this
      function, likely not demanding the direct binding of E2 to cognate DNA sites,
      might primarily involve protein-protein interactions.

PMID- 9261406
TI  - Identification and elimination of replication-competent adeno-associated virus
      (AAV) that can arise by nonhomologous recombination during AAV vector production.
AB  - Adeno-associated virus (AAV) vector preparations are often contaminated with
      variable amounts of replication-competent AAV (rcAAV), which may influence the
      behavior of these vectors both in cultured cells and in animals. A packaging
      plasmid/vector plasmid system containing no significant homology and lacking the
      wild-type AAV p5 promoter was constructed to eliminate the production of wild
      type AAV by recombination. Still, rcAAV was detected in vector produced by
      cotransfection of these plasmids at large scale. Sequence analysis revealed that
      nonhomologous recombination was responsible for the generation of these novel
      rcAAVs. A new AAV packaging plasmid carrying separate rep and cap expression
      cassettes in opposite transcriptional orientations was constructed. AAV vector
      preparations produced by using this packaging construct did not contain rcAAV.

PMID- 9261407
TI  - Cloning of adeno-associated virus type 4 (AAV4) and generation of recombinant
      AAV4 particles.
AB  - We have cloned and characterized the full-length genome of adeno-associated virus
      type 4 (AAV4). The genome of AAV4 is 4,767 nucleotides in length and contains an
      expanded p5 promoter region compared to AAV2 and AAV3. Within the inverted
      terminal repeat (ITR), several base changes were identified with respect to AAV2.
      However, these changes did not affect the ability of this region to fold into a
      hairpin structure. Within the ITR, the terminal resolution site and Rep binding
      sites were conserved; however, the Rep binding site was expanded from three GAGC
      repeats to four. The Rep gene product of AAV4 shows greater than 90% homology to
      the Rep products of serotypes 2 and 3, with none of the changes occurring in
      regions which had previously been shown to affect the known functions of Rep68 or
      Rep78. Most of the differences in the capsid proteins lie in regions which are
      thought to be on the exterior surface of the viral capsid. It is these unique
      regions which are most likely to be responsible for the lack of cross-reacting
      antibodies and the altered tissue tropism compared to AAV2. The results of our
      studies, performed with a recombinant version of AAV4 carrying a lacZ reporter
      gene, suggest that AAV4 can transduce human, monkey, and rat cells. Furthermore,
      comparison of transduction efficiencies in a number of cell lines, competition
      cotransduction experiments, and the effect of trypsin on transduction efficiency
      all suggest that the cellular receptor for AAV4 is distinct from that of AAV2.

PMID- 9261408
TI  - Human immunodeficiency virus matrix tyrosine phosphorylation: characterization of
      the kinase and its substrate requirements.
AB  - During virus assembly, a subset of human immunodeficiency virus (HIV) matrix (MA)
      molecules is phosphorylated on C-terminal tyrosine. This modification facilitates
      infection of nondividing cells by allowing for the recruitment of the karyophilic
      MA into the viral core and preintegration complex. MA tyrosine phosphorylation is
      accomplished by a cellular protein kinase which is incorporated into virions. In
      this study, we have investigated the nature of this enzyme as well as the
      determinants of MA necessary for its phosphorylation. Employing an in vitro
      kinase assay, we found that the MA tyrosine kinase activity is present in various
      cultured cell lines including CEM and SupT1 T-lymphoid cells, Namalwa B cells,
      293 and CV-1 kidney fibroblasts, and P4 HeLa cells. In addition, it could be
      detected in platelets, macrophages, and activated peripheral blood lymphocytes
      (PBLs) but not in erythrocytes and resting PBLs isolated from human blood.
      Subcellular localization of the kinase activity by cell fractionation
      demonstrated that it is enriched in cellular membranes. In HIV type 2 (HIV-2)
      particles, the MA tyrosine kinase is associated with the inner leaflet of the
      viral membrane, while the tyrosine-phosphorylated MA is localized to the core.
      Individual mutations of each of the last eight residues immediately upstream of
      the C-terminal tyrosine (Y132) of HIV-1 MA did not prevent Y132 phosphorylation,
      suggesting that the kinase does not require a highly specific sequence adjacent
      to the C-terminal tyrosine. Confirming this, we found that the MA of murine
      leukemia virus, the sequence of which is only moderately homologous to that of
      HIV-1 and HIV-2 MA, is also C-terminally tyrosine phosphorylated.

PMID- 9261409
TI  - Direct repeats of the herpes simplex virus a sequence promote nonconservative
      homologous recombination that is not dependent on XPF/ERCC4.
AB  - We have examined mechanisms of recombination in mammalian cells infected with
      herpes simplex virus type 1 (HSV-1). Amplification of plasmids containing a viral
      origin of replication, oriS, in cells superinfected with HSV-1 revealed that
      linear DNA could be efficiently converted to templates for replication. Two
      distinct pathways were observed: imprecise end joining and nonconservative
      homologous recombination. We noted that direct repeats of the viral a sequence
      promoted efficient nonconservative homologous recombination in BHK cells as well
      as human repair-proficient 1BR.3N cells and xeroderma pigmentosum group F (XP-F)
      cells. The reaction gave rise to functional a sequences supporting the formation
      of defective viruses. It did not seem to proceed by single-strand annealing since
      it occurred in the absence of XPF/ERCC4, the mammalian homolog of the Rad1
      endonuclease from Saccharomyces cerevisiae. In contrast, direct repeats of a 161
      bp nonviral sequence did not take part in nonconservative homologous
      recombination in XP-F cells. Our results suggest that homologous recombination
      may be involved in the circularization of viral genomes. Furthermore, they
      demonstrate that amplification of recombination products supported by HSV-1
      allows a direct examination of pathways for double-strand-break repair in human
      cells.

PMID- 9261411
TI  - Cryo-electron microscopy structure of yeast Ty retrotransposon virus-like
      particles.
AB  - The virus-like particles (VLPs) produced by the yeast retrotransposon Ty1 are
      functionally related to retroviral cores. These particles are unusual in that
      they have variable radif. A paired mass-radius analysis of VLPs by scanning
      transmission electron microscopy showed that many of these particles form an
      icosahedral T-number series. Three-dimensional reconstruction to 38-A resolution
      from cryo-electron micrographs of T = 3 and T = 4 shells revealed that the single
      structural protein encoded by the TYA gene assembles into spiky shells from
      trimeric units.

PMID- 9261412
TI  - Human immunodeficiency virus type 1 mutants that escape neutralization by human
      monoclonal antibody IgG1b12. off.
AB  - IgG1b12, a human monoclonal antibody (MAb) to an epitope overlapping the CD4
      binding site on gp120, has broad and potent neutralizing activity against most
      primary human immunodeficiency virus type 1 (HIV-1) isolates. To assess whether
      and how escape mutants resistant to IgG1b12 can be generated, we cultured primary
      HIV-1 strain JRCSF in its presence. An escape mutant emerged which was
      approximately 100-fold more resistant to neutralization by IgG1b12. Both virion
      associated and solubilized gp120 from this variant had a reduced affinity for
      IgG1b12, and sequencing of its env gene showed that amino acid substitutions had
      occurred at three positions within gp120. Two (D164N and D182N) were located in
      V2, and one (P365L) was in C3. By site-directed mutagenesis, we demonstrated that
      the D182N and P365L mutations, but not D164N, contribute to the IgG1b12-resistant
      phenotype. However, the former two substitutions, individually or in combination,
      hinder the replication of the neutralization-resistant virus. Introduction of the
      D164N substitution into the P365L variant results in a nonviable virus
      (D164N/P365L). In contrast, addition of D164N to the D182N or D182N/P365L mutant
      partially restored replicative function to near wild-type levels. Furthermore, we
      found that all of the IgG1b12-resistant mutant viruses remained sensitive to
      other human MAbs, such as 2G12 and 2F5, and to the CD4-IgG molecule, except that
      the P365L-containing mutant was slightly resistant to CD4-IgG. These results
      suggest that escape from IgG1b12 neutralization is due to a local rather than a
      global modification of the gp120 structure. Our findings have implications for
      the therapeutic and prophylactic applications of antibodies for HIV-1 infection.

PMID- 9261410
TI  - Activation of gene expression by herpes simplex virus type 1 ICP0 occurs at the
      level of mRNA synthesis.
AB  - ICP0 is a nuclear phosphoprotein involved in the activation of herpes simplex
      virus type 1 (HSV-1) gene expression during lytic infection and reactivation from
      viral latency. Although available evidence suggests that ICP0 acts at the level
      of transcription, definitive studies specifically addressing this issue have not
      been reported. In the present study we measured the ability of ICP0 to activate
      gene expression (i) from promoters representing the major kinetic classes of
      viral genes in transient expression assays and (ii) from the same promoters
      during viral infection at multiplicities of infection ranging from 0.1 to 5.0
      PFU/cell. The levels of synthesis and steady-state accumulation of mRNA, mRNA
      stability, and levels of protein synthesis were compared in cells transfected
      with a reporter plasmid in the presence and absence of ICP0 and in cells infected
      with wild-type HSV-1 or an ICP0 null mutant, n212. In transient expression assays
      and during viral infection at all multiplicities tested, the levels of steady
      state mRNA and protein were significantly lower in the absence of ICP0,
      indicating that ICP0 activates gene expression at the level of mRNA accumulation.
      In transient expression assays and during infection at low multiplicities (< 1
      PFU/cell) in the presence or absence of ICP0, marked increases in the levels of
      viral mRNAs accompanied by proportional increases in the levels of protein
      synthesis were observed with increasing multiplicity. At a high multiplicity (5
      PFU/cell) in the presence or absence of ICP0, mRNA levels did not increase as a
      function of multiplicity and changes in the levels of protein were no longer
      related to changes in the levels of mRNA. Collectively, these tests indicate that
      transcription of viral genes is rate limiting at low multiplicities and that
      translation is rate limiting at high multiplicities, independent of ICP0.
      Consistent with the lower levels of mRNA detected in the absence of ICP0, the
      rates of transcription initiation measured by nuclear run-on assays were
      uniformly lower in cells infected with the ICP0 null mutant at all multiplicities
      tested, implying that ICP0 enhances transcription at or before initiation or
      both. No evidence was found of posttranscriptional effects of ICP0 (i.e., effects
      on the stability of mRNA, nuclear-cytoplasmic distribution, polyribosomal mRNA
      distribution, or rates of protein synthesis). Taken together, these results
      suggest that ICP0 activates gene expression prior to or at the level of
      initiation of mRNA synthesis in transient expression assays and during viral
      infection. Based on these findings; we hypothesize that the exaggerated
      multiplicity-dependent growth phenotype characteristic of ICP0 null mutants
      reflects the requirement for ICP0 under conditions where the steady-state level
      of mRNA is rate limiting, such as during low-multiplicity infection and
      reactivation from latency.

PMID- 9261413
TI  - Sequence variation within a nonstructural region of the hepatitis G virus genome.
AB  - Nine sets of nested PCR primers from a 2.6-kb region of the hepatitis G virus
      (HGV) genome at nucleotide positions 5829 to 8421 were designed and used to
      analyze serum specimens obtained from patients with community-acquired non-A, non
      B hepatitis who were HGV RNA positive. One set of primers was found to be most
      efficient in detecting HGV and was subsequently used to test 162 HCV-positive and
      11 HCV-negative plasma units obtained from individual paid donors. HGV RNA was
      detected in 30 (17.3%) plasma units, 2 of which were found among the 11 HCV
      negative specimens. A complete set of nine PCR fragments was obtained from two
      patients with community-acquired acute non-A, non-B hepatitis and from four paid
      donors. All PCR fragments were sequenced and were shown to have a nucleotide
      similarity of 85.9 to 92.3% and a derived amino acid similarity of 96.0 to 99.0%.
      The majority of nucleotide changes occurred in the third position of codons. The
      HGV nucleotide and protein sequences obtained in this study were compared with
      HCV sequences. Based on this analysis the 2.6-kb fragment was predicted to encode
      the C-terminal part of the putative NS4b, the entire NS5a, and almost the
      complete NS5b proteins. Putative protease cleavage sites separating these
      proteins were also predicted. In serial specimens obtained from the two HGV
      infected patients, no significant variations were found in the HGV nucleotide and
      derived amino acid sequences over time. The HGV sequences obtained from one
      patient showed no changes over 6 months, whereas more than 99.0% homology was
      observed for sequences from the second patient over 2.5 years. Heterogeneity
      analysis performed on 10 sequences obtained in this study and corresponding
      regions from 6 known full-size sequences of the HGV genomes demonstrated notable
      discrete heterogeneity consistent with the existence of HGV genetic groups or
      types.

PMID- 9261414
TI  - Poliovirus-encoded protease 2APro cleaves the TATA-binding protein but does not
      inhibit host cell RNA polymerase II transcription in vitro.
AB  - Transient expression of the poliovirus-encoded protease 2APro in eukaryotic cells
      results in inhibition of both cellular transcription and translation. The
      inhibition of transcription observed in cells expressing 2APro could be due to a
      primary effect or secondary effect caused by inhibition of translation. Because
      transcriptional activity of the TATA-binding protein (TBP) is drastically reduced
      in poliovirus-infected cells, we determined if 2APro is able to cleave TBP in
      vitro. We demonstrate here that 2APro directly cleaves the single tyrosine
      glycine bond at position 34 of TBP. This cleavage is also seen in poliovirus
      infected HeLa cells. Surprisingly, despite TBP cleavage 2APro was unable to
      inhibit RNA polymerase II transcription in vitro. Under similar conditions,
      however, 2APro inhibited translation of a capped cellular mRNA in vitro. Thus,
      cleavage of TBP at position 34 does not alter its transcriptional activity in
      vitro. These results suggest that inhibition of host cell RNA polymerase II
      transcription seen in cells transiently transfected with 2APro is due to host
      cell translational shutoff.

PMID- 9261416
TI  - The autonomous growth of human papillomavirus type 16-immortalized keratinocytes
      is related to the endothelin-1 autocrine loop.
AB  - Some human papillomaviruses (HPVs) such as HPV type 16 (HPV16) and HPV18 are
      involved in cervical carcinoma, and they can immortalize and transform
      keratinocytes. Endothelin-1 (ET-1) is produced in keratinocytes and has been
      shown to act through ETA receptors as an autocrine growth factor for
      keratinocytes. This study examines whether HPV16 alters the ET-1-mediated
      autocrine loop in human keratinocytes, providing a selective growth advantage for
      transformed cells. ET-1 is released in similar amounts from normal and HPV
      transfected keratinocytes. All HPV-transfected cell lines express high-affinity
      ETA receptors. A two-fold increase in ET-1 binding sites is present in HPV16
      immortalized keratinocytes, and this effect seems to be linked to the
      overexpression of mRNA for this receptor rather than to differences in the
      surface/internalized ratio of the receptors. ET-1 induces significant increases
      in [3H]thymidine incorporation and cell proliferation. Furthermore, HPV
      transfected keratinocytes can proliferate in the absence of any growth factor
      added to the growth medium, and the ETA receptor antagonist BQ123 prevents this
      proliferation. These data suggest a new mechanism in the growth control of HPV
      transformed cells mediated by the upregulation of ET-1 autocrine loop.

PMID- 9261415
TI  - Interferon-independent and -induced regulation of Epstein-Barr virus EBNA-1 gene
      transcription in Burkitt lymphoma.
AB  - Replication of the Epstein-Barr virus (EBV) genome within latently infected cells
      is dependent on the EBV EBNA-1 protein. The objective of this study was to
      identify transcriptional regulatory proteins that mediate EBNA-1 expression via
      the viral promoter Qp, which is active in EBV-associated tumors such as Burkitt
      lymphoma and nasopharyngeal carcinoma. Results of a yeast one-hybrid screen
      suggested that a subset of the interferon regulatory factor (IRF) family may
      regulate EBNA-1 transcription by targeting an essential cis-regulatory element of
      Qp, QRE-2. Further investigation indicated that the transcriptional activator IRF
      1 and the closely related IRF-2, a repressor of interferon-induced gene
      expression, are both capable of activating Qp. However, the major QRE-2-specific
      binding activity detected within extracts of Burkitt lymphoma cells was
      attributed to IRF-2, suggesting that interferon-independent activation of Qp is
      largely mediated by IRF-2 in these cells. We observed no effect of gamma
      interferon on Qp activity in transfection assays, whereas we observed a moderate
      but significant repression of Qp activity in response to alpha interferon,
      possibly mediated by either the interferon consensus sequence binding protein or
      IRF-7, a novel alpha interferon-inducible factor identified in this study. Since
      expression of IRF-1 and IRF-2 is increased in response to interferons, the Qp
      activity observed in the presence of interferon likely represented an equilibrium
      between IRF factors that activate and those that repress gene expression in
      response to interferon. Thus, by usurping both IRF-1 and its transcriptional
      antagonist IRF-2 to activate Qp, EBV has evolved not only a mechanism to
      constitutively express EBNA-1 but also one which may sustain EBNA-1 expression in
      the face of the antiviral effects of interferon.

PMID- 9261418
TI  - Varicella-zoster virus glycoprotein I is essential for growth of virus in Vero
      cells.
AB  - Varicella-zoster virus (VZV) encodes at least six glycoproteins. Glycoprotein I
      (gI), the product of open reading frame 67, is a 58- to 62-kDa glycoprotein found
      in VZV-infected cells. We constructed two VZV gI deletion mutants.
      Immunoprecipitation of VZV gE from infected cells indicated that cells infected
      with VZV deleted for gI expressed a gE that was larger (100 kDa) than that
      expressed in cells infected with the parental virus (98 kDa). Cell-associated or
      cell-free VZV deleted for gI grew to lower titers in melanoma cells than did
      parental VZV. While VZV deleted for gI replicated in other human cells, the
      mutant virus replicated to very low titers in primary guinea pig and monkey cells
      and did not replicate in Vero cells. When compared with the parental virus,
      rescued viruses, in which the gI deletion was restored with a wild-type allele,
      showed a similarly sized gE and comparable growth patterns in melanoma and Vero
      cells. VZV deleted for gI entered Vero cells; however, viral DNA synthesis was
      impaired in these cells. The VZV gI mutant was slightly impaired for adsorption
      to human cells. Thus, VZV gI is required for replication of the virus in Vero
      cells, for efficient replication of the virus in nonhuman cells, and for normal
      processing of gE.

PMID- 9261417
TI  - Poliovirus Sabin type 1 neutralization epitopes recognized by immunoglobulin A
      monoclonal antibodies.
AB  - Immunity to poliomyelitis is largely dependent on humoral neutralizing
      antibodies, both after natural (wild virus or vaccine) infection and after
      inactivated poliovirus vaccine inoculation. Although the production of local
      secretory immunoglobulin A (IgA) antibody in the gut mucosa may play a major role
      in protection, most of information about the antigenic determinants involved in
      neutralization of polioviruses derives from studies conducted with humoral
      monoclonal antibodies (MAbs) generated from parenterally immunized mice. To
      investigate the specificity of the mucosal immune response to the virus, we have
      produced a library of IgA MAbs directed at Sabin type 1 poliovirus by oral
      immunization of mice with live virus in combination with cholera toxin. The
      epitopes recognized by 13 neutralizing MAbs were characterized by generating
      neutralization-escape virus mutants. Cross-neutralization analysis of viral
      mutants with MAbs allowed these epitopes to be divided into four groups of
      reactivity. To determine the epitope specificity of MAbs, virus variants were
      sequenced and the mutations responsible for resistance to the antibodies were
      located. Eight neutralizing MAbs were found to be directed at neutralization site
      N-AgIII in capsid protein VP3; four more MAbs recognized site N-AgII in VP1 or
      VP2. One IgA MAb selected a virus variant which presented a unique mutation at
      amino acid 138 in VP2, not previously described. This site appears to be
      partially related with site N-AgII and is located in a loop region facing the VP2
      N-Ag-II loop around residue 164. Only 2 of 13 MAbs proved able to neutralize the
      wild-type Mahoney strain of poliovirus. The IgA antibodies studied were found to
      be produced in the dimeric form needed for recognition by the polyimmunoglobulin
      receptor mediating secretory antibody transport at the mucosal level.

PMID- 9261419
TI  - Cyclophilin A-induced alterations of human immunodeficiency virus type 1 CA
      protein in vitro.
AB  - Cyclophilin A (CyP A), a cellular chaperone with cis-trans prolyl isomerase
      activity, is required for postassembly events in human immunodeficiency virus
      type 1 (HIV-1) replication. The requirement for CyP A maps to sequences in the
      capsid (CA) domain of the structural precursor, Gag. To determine the effects of
      interaction with CyP A on capsid (CA) protein structure, the binding interaction
      was investigated in vitro, using recombinant HIV-1 CA protein (which forms
      oligomers in solution) and human CyP A. The CA and CyP A proteins interacted to
      form a complex which was detected predominantly as a heterodimer on sodium
      dodecyl sulfate (SDS)-polyacrylamide gels. Complex formation exhibited a pH
      optimum of 5. The CA protein in the complex was exclusively in a conformation
      whereby the N terminus was blocked to Edman degradation. This finding was
      unexpected since CyP A binds to the central region of the CA protein (residues 85
      to 93). Examination of CA protein incubated with CyP A for alterations in
      structure indicated that CyP A preferentially interacted with the subpopulation
      of trypsin-susceptible subunits in the oligomers and significantly reduced their
      sensitivity to proteolysis. Like CA-CyP A complex formation, conversion to
      trypsin resistance also exhibited a pH optimum of 5. Both complex formation and
      the changes in tryptic susceptibility were only partially inhibited by
      cyclosporin A (CsA). This appeared to be due to a CA subpopulation able to bind
      CyP A despite the presence of CsA. Our results identify specific tryptic sites
      both proximal and distal to the CyP A binding region that are altered by CyP A
      binding and/or by CyP A's prolyl isomerase activity. Comparison with the X-ray
      structure of a complex containing CyP A bound to an amino-terminal fragment of
      the CA protein (CA1-151) (T.R. Gamble et al., Cell 87:1285-1294, 1996) indicates
      that the tryptic sites that become inaccessible are among the same residues that
      lose a significant amount of accessible surface area through CA-CA subunit
      contacts made in the presence of CyP A.

PMID- 9261420
TI  - CXCR4 expression during lymphopoiesis: implications for human immunodeficiency
      virus type 1 infection of the thymus.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection of the human thymus results
      in depletion of CD4-bearing thymocytes. This depletion is initially manifested in
      the immature CD4+/CD8+ thymocyte subset. To determine cellular factors involved
      in HIV infection in the thymus, we examined the expression of the recently
      identified viral coreceptor, CXCR4, on fresh human thymocytes and on human cells
      from SCID-hu (Thy/Liv) mice. CXCR4 is a member of the chemokine receptor family
      which is required along with CD4 for entry into the cell of syncytium-inducing
      (SI) HIV-1 strains. Our analyses show that CXCR4 expression is modulated during T
      lymphoid differentiation such that immature thymocytes display an increased
      frequency and higher surface density of the coreceptor than do more mature cells.
      In addition, using an SI strain of HIV-1 which directs expression of a reporter
      protein on the surface of infected cells, we have found that the immature
      CD4+/CD8+ thymocytes that express the highest levels of both CD4 and CXCR4 are
      the cells that are preferentially infected and depleted by the virus in vitro.
      Thus, high levels of both primary receptor and coreceptor may allow efficient
      infection of the thymus by certain HIV-1 strains. This in part may explain the
      rapid disease progression seen in some HIV-infected children, where the thymus is
      actively involved in the production of new T lymphocytes.

PMID- 9261421
TI  - Priming with live respiratory syncytial virus (RSV) prevents the enhanced
      pulmonary inflammatory response seen after RSV challenge in BALB/c mice immunized
      with formalin-inactivated RSV.
AB  - To investigate enhanced disease associated with a formalin-inactivated (FI)
      respiratory syncytial virus (RSV) vaccine, we studied the pulmonary inflammatory
      response to RSV in BALB/c mice immunized with live RSV, FI-RSV, or combinations
      of the two. After RSV challenge, the number of granular cells, the ratio of
      CD4+/CD8+ lymphocytes, and the level of Th2-like cytokine mRNAs in the
      bronchoalveolar lavage specimens in mice immunized first with live RSV and then
      with FI-RSV were lower than that in FI-RSV-immunized mice and close to that in
      live RSV-immunized mice. These data suggest that prior live RSV infection
      prevents most of the enhanced inflammatory response seen in FI-RSV-immunized mice
      and might explain lack of enhanced disease in older FI-RSV-immunized children. A
      live RSV vaccine might similarly decrease the risk of enhanced disease with non
      live RSV vaccines.

PMID- 9261422
TI  - Placement of tRNA primer on the primer-binding site requires pol gene expression
      in avian but not murine retroviruses.
AB  - In an early step in the retroviral infectious process, reverse transcriptase
      copies the genomic RNA of the virus into complementary minus-strand DNA. The
      primer for this synthetic event is a molecule of cellular tRNA, which is annealed
      by its 3' 18 nucleotides to a region of the genomic RNA termed the primer-binding
      site (PBS); the sequence of the PBS and hence the identity of the tRNA depend
      upon the retrovirus species. In addition to the primer tRNA, retrovirus particles
      contain a substantial number of other tRNA molecules. The latter tRNA population
      is enriched for the tRNA species which serves as primer for the virus. While
      there is considerable evidence that the enrichment for the primer species can be
      attributed to the pol gene product, nothing is known regarding mechanisms of
      annealing the primer to the PBS. We have analyzed pol- mutants of avian leukosis
      virus (ALV) and murine leukemia virus (MuLV) for the presence of primer at the
      PBS in virion genomic RNA. Remarkably, the results were different for the two
      viruses: the PBS was substantially occupied by primer in MuLV but not in ALV.
      Previous data indicates that the Pol-dependent enrichment of the primer within
      the virion is much greater in ALV than in MuLV. We therefore propose that the
      absence of primer at the PBS in pol- ALV is due to the deficiency of the primer
      species within the particle. The results suggest that, at least in MuLV, the tRNA
      is unwound by either the Gag protein or a cellular protein for annealing to the
      PBS. Further, the C-terminal 17 amino acids of Gag are unnecessary for this
      function in MuLV.

PMID- 9261423
TI  - cis elements that contribute to geminivirus transcriptional regulation and the
      efficiency of DNA replication.
AB  - The A genomic component of the geminivirus tomato golden mosaic virus (TGMV)
      contains a 5' intergenic sequence that includes the overlapping AL61 promoter and
      positive-strand origin of DNA replication. The TGMV AL1 protein negatively
      regulates its own transcription and mediates origin recognition by binding to a
      repeated motif shared by the AL61 promoter and the viral origin. We examined a
      series of truncated or mutated 5' intergenic regions in transient expression and
      replication assay to identify other DNA sequences that contribute to TGMV
      promoter and origin function. These experiments revealed that negative regulation
      of the AL61 promoter is complex, involving multiple cis-acting sequences and the
      AL1 and AL4 proteins, which acted through different DNA elements. We also found
      that mutation of the TATA box motif in the AL61 promoter reduced overall
      transcriptional activity and AL1-mediated repression, confirming the importance
      of this sequence in promoter function. Mutation of a G-box consensus sequence was
      highly detrimental to AL61 transcription and abolished AL1 sensitivity,
      suggesting that AL1 interferes with transcriptional activation. Cotransfection
      experiments showed that the TATA box and G-box motif mutations also impaired
      viral DNA replication in the presence of a wild-type origin but had no effect in
      its absence, demonstrating that these transcriptional motifs also function as
      replication efficiency elements.

PMID- 9261424
TI  - Cell-type-specific separate regulation of the E6 and E7 promoters of human
      papillomavirus type 6a by the viral transcription factor E2.
AB  - Gene expression of human papillomaviruses (HPV) is tightly controlled by cellular
      factors and by the virally encoded E2 protein through binding to distinct sites
      within the regulatory noncoding region. While for the high-risk genital
      papillomaviruses a single promoter drives the expression of all early genes, a
      second promoter present in the E6 open reading frame of the low-risk HPV type 6
      (HPV6) would allow an independent regulation of E6 and E7 oncogene expression. In
      this report, we provide the first evidence that E2 regulates both early promoters
      of HPV6 separately and we show that promoter usage as well as E2 regulation is
      cell type dependent. Among the different epithelial cell lines tested, only RTS3b
      cells allowed an expression pattern similar to that observed in naturally
      infected benign condylomas. While the E6 promoter was repressed by E2 to 50% of
      its basal activity, the E7 promoter was simultaneously stimulated up to fivefold.
      Activation of the E7 promoter was mediated predominantly by the binding of E2 to
      the most promoter-distal E2 binding site. Repression of the E6 promoter depended
      on the presence of two intact promoter-proximal binding sites. Mutation of both
      of these repressor binding sites reversed the effect of E2 on the E6 promoter
      from repression to activation. In contrast, in HT3 cells we observed an E2
      mediated activation of the E6 promoter in the context of the wild-type noncoding
      region. This indicated that repression of the E6 promoter by binding of E2 to
      both promoter-proximal binding sites did not function in the cellular environment
      provided by HT3 cells. These data suggest that the separate regulation of the E6
      and E7 promoters of HPV6 is mediated through successive occupation of binding
      sites with different affinities for E2 depending on the intracellular
      concentration of E2 and on the cellular environment provided by the infected
      cell.

PMID- 9261425
TI  - Functional interactions between monomers of the retroviral envelope protein
      complex.
AB  - Retroviral vectors have been widely used in human gene therapy protocols. Entry
      into target cells is directed by the retroviral envelope protein, with receptor
      binding and postbinding fusion functions contributed mainly by the SU and TM
      subunits, respectively. We have generated mutants of the Moloney murine leukemia
      virus (MoMuLV) envelope protein with mutations in both the receptor binding
      domain of SU and throughout the TM subunit that are functionally inactive when
      expressed individually. However, the coexpression of these two classes of mutants
      partially restores envelope protein function and allows transduction. Several
      lines of evidence indicate that this complementation occurs in trans within
      envelope protein heterooligomers. The finding that the binding and postbinding
      functions of a retroviral envelope protein can be contributed by two different
      monomers should assist in the engineering of envelope proteins for tissue
      specific gene delivery.

PMID- 9261426
TI  - Mutations in the N-terminal domain of human immunodeficiency virus type 1
      nucleocapsid protein affect virion core structure and proviral DNA synthesis.
AB  - Nucleocapsid protein NCp7 of human immunodeficiency virus type 1 (HIV-1) is a
      small basic nucleic acid binding protein containing two zinc fingers of the form
      (CX2CX4HX4C) and is present at about 2,000 copies inside the viral core. NCp7
      molecules are tightly associated with the genomic RNA dimer to form the
      nucleocapsid, which also includes reverse transcriptase and integrase proteins.
      In vitro, NCp7 has been shown to bind specifically to HIV-1 RNA, inducing NCp7
      NCp7 interactions. In the viral context, mutagenesis of amino acid residues in
      the zinc finger domains showed that NCp7 is responsible for the specific
      incorporation of genomic RNA into virions and is necessary for correct virion
      assembly and maturation. In this work, we investigated the consequences of
      mutating conserved basic residues in the N-terminal region that precedes the
      first zinc finger. Two of the mutants were poorly infectious and showed only
      limited, though significant, defects in RNA encapsidation and viral protein
      maturation. Electron microscopy, together with sucrose gradient analysis,
      revealed defects in particle core structure and heterogeneity among mutant
      virions. These defects were associated with strong reduction of proviral DNA
      synthesis and stability in newly infected cells. Taken together, these data show
      multiple and probably interdependent implications for the NCp7 protein in both
      early and late phases of the HIV-1 replicative cycle and emphasize it as a target
      for antiviral drug development.

PMID- 9261427
TI  - Induction of tumor necrosis factor alpha in human neuronal cells by extracellular
      human T-cell lymphotropic virus type 1 Tax.
AB  - To examine the role of human T-lymphotropic virus type 1 (HTLV-1) Tax1 in the
      development of neurological disease, we studied the effects of extracellular Tax1
      on gene expression in NT2-N cells, postmitotic cells that share morphologic,
      phenotypic, and functional features with mature human primary neurons. Treatment
      with soluble HTLV-1 Tax1 resulted in the induction of tumor necrosis factor alpha
      (TNF-alpha) gene expression, as detected by reverse-transcribed PCR and by enzyme
      linked immunosorbent assay. TNF-alpha induction was completely blocked by
      clearance with anti-Tax1 monoclonal antibodies. Furthermore, cells treated with
      either a mock bacterial extract or with lipopolysaccharide produced no detectable
      TNF-alpha. Synthesis of TNF-alpha in response to soluble Tax1 occurred in a dose
      dependent fashion between 0.25 and 75 nM and peaked within 6 h of treatment.
      Interestingly, culturing NT2-N cells in the presence of soluble Tax1 for as
      little as 5 min was sufficient to result in TNF-alpha production, indicating that
      the induction of TNF-alpha in NT2-N does not require Tax1 to be continually
      present in the culture medium. Treatment of the undifferentiated parental
      embryonal carcinoma cell line NT2 with soluble Tax1 did not result in TNF-alpha
      synthesis, suggesting that differentiation-dependent, neuron-specific factors may
      be required. These results provide the first experimental evidence that neuronal
      cells are sensitive to HTLV-1 Tax1 as an extracellular cytokine, with a potential
      role in the pathology of HTLV-1-associated/tropical spastic paraparesis.

PMID- 9261428
TI  - Multimerization of polyomavirus middle-T antigen.
AB  - The oncogenic protein of polyomavirus, middle-T antigen, associated with cell
      membranes and interacts with a variety of cellular proteins involved in mitogenic
      signalling. Middle-T antigen may therefore mimic the function of cellular
      tyrosine kinase growth factor receptors, like the platelet-derived growth factor
      or epidermal growth factor receptor. Growth factor receptor signalling is
      initiated upon the binding of a ligand to the extracellular domain of the
      receptor. This results in activation of the intracellular tyrosine kinase domain
      of the receptor, followed by receptor phosphorylation, presumably as a
      consequence of dimerization of two receptor molecules. Similar to middle-T
      antigen, phosphorylation of growth factor receptors leads to recruitment of
      cellular signalling molecules downstream in the signalling cascade. In this
      study, we investigated whether middle-T antigen, similar to tyrosine kinase
      growth factor receptors, is able to form dimeric signalling complexes. We found
      that association with cellular membranes was a prerequisite for multimerization,
      most likely dimer formation. A chimeric middle-T antigen carrying the membrane
      targeting sequence of the vesicular stomatitis virus G protein instead of the
      authentic polyomavirus sequence still dimerized. However, mutants of middle-T
      antigen unable to associate with 14-3-3 proteins, like d18 and S257A, did not
      form dimers but were still oncogenic. This indicates that both membrane
      association and binding of 14-3-3 are necessary for dimer formation of middle-T
      antigen but that only the former is essential for cell transformation.

PMID- 9261430
TI  - Differential divalent cation requirements uncouple the assembly and catalytic
      reactions of human immunodeficiency virus type 1 integrase.
AB  - Previous in vitro analyses have shown that the human immunodeficiency virus type
      1 (HIV-1) integrase uses either manganese or magnesium to assemble as a stable
      complex on the donor substrate and to catalyze strand transfer. We now
      demonstrate that subsequent to assembly, catalysis of both 3' end processing and
      strand transfer requires a divalent cation cofactor and that the divalent cation
      requirements for assembly and catalysis can be functionally distinguished based
      on the ability to utilize calcium and cobalt, respectively. The different
      divalent cation requirements manifest by these processes are exploited to
      uncouple assembly and catalysis, thus staging the reaction. Staged 3' end
      processing and strand transfer assays are then used in conjunction with
      exonuclease III protection analysis to investigate the effects of integrase
      inhibitors on each step in the reaction. Analysis of a series of related
      inhibitors demonstrates that these types of compounds affect assembly and not
      either catalytic process, therefore reconciling the apparent disparate results
      obtained for such inhibitors in assays using isolated preintegration complexes.
      These studies provide evidence for a distinct role of the divalent cation
      cofactor in assembly and catalysis and have implications for both the
      identification and characterization of integrase inhibitors.

PMID- 9261429
TI  - Mutational analysis of the adeno-associated virus type 2 Rep68 protein helicase
      motifs.
AB  - The adeno-associated virus type 2 (AAV) Rep78 and Rep68 proteins are required for
      viral replication. These proteins are encoded by unspliced and spliced
      transcripts, respectively, from the p5 promoter of AAV and therefore have
      overlapping amino acid sequences. The Rep78 and Rep68 proteins share a variety of
      activities including endonuclease, helicase, and ATPase activities and the
      ability to bind AAV hairpin DNA. The part of the amino acid sequence which is
      identical in Rep78 and Rep68 contains consensus helicase motifs that are
      conserved among the parvovirus replication proteins. In the present study, we
      mutated highly conserved amino acids within these helicase motifs. The mutant
      proteins were synthesized as maltose binding protein-Rep68 fusions in Escherichia
      coli cells and affinity purified on amylose resin. The fusion proteins were
      assayed in vitro, and their activities were directly compared to those of the
      fusion protein MBP-Rep68 delta, which contains most of the amino acid sequences
      common to Rep78 and Rep68 and was demonstrated previously to have all of the in
      vitro activities of wild-type Rep78 and Rep68. Our analysis showed that almost
      all mutations in the putative helicase motifs severely reduced or abolished
      helicase activity in vitro. Most mutants also had ATPase activity less than one
      eighth of the wild-type levels and lacked endonuclease activity.

PMID- 9261431
TI  - The critical N-linked glycan of murine leukemia virus envelope protein promotes
      both folding of the C-terminal domains of the precursor polyprotein and stability
      of the postcleavage envelope complex.
AB  - The infectivity of Friend ecotropic murine leukemia virus was previously shown to
      be highly sensitive to modification in its envelope protein (Env) at only one of
      the eight signals for N-linked glycan attachment, the fourth from the N terminus
      (gs4). In the present study, a set of six single-amino-acid substitutions in or
      near gs4 was used to determine the function of this region of Env and the role
      played by the glycan itself. One mutant that lacked the gs4 glycan was fully
      infectious, while one that retained this glycan was completely noninfectious,
      indicating that the gs4 glycan per se is not required for Env function.
      Infectivity correlated with the level of mature Env complex incorporated into
      virus particles, which was determined by the severity of defects in transport of
      the envelope precursor protein (gPrEnv) from the endoplasmic reticulum into the
      Golgi apparatus, in cleavage of gPrEnv into the two envelope subunits (the
      surface protein [SU] and the transmembrane protein [TM]), and in the association
      of SU with cellular membranes. All of the mutants induced the wild-type level of
      superinfection interference, indicating that the gs4 region mutations did not
      interfere with proper folding of the N-terminal domain of SU. These results
      suggest that the gs4 region mediates folding of the C-terminal domains of gPrEnv
      and stability of the interaction between SU and TM. Although the gs4 glycan was
      not essential for infectivity, processing of all mutant Envs lacking this glycan
      was significantly impaired, suggesting that efficient folding of gPrEnv requires
      a glycan at this position. The conservation of a glycosylation site homologous to
      gs4 across a broad range of retroviruses suggests that this sequence may play a
      similar role in many retroviral Envs.

PMID- 9261432
TI  - Cell and viral regulatory elements enhance the expression and function of a human
      immunodeficiency virus inhibitory gene.
AB  - Regulated expression of recombinant genes in CD4+ cells is an important objective
      for gene therapy of AIDS, as these cells represent the principal target for viral
      replication of human immunodeficiency virus (HIV). We report here that specific
      combinations of CD4 cell-specific and viral regulatory elements can enhance
      expression of an antiviral gene product. Different viral regulatory elements were
      incorporated into a previously reported CD4 locus control region to increase the
      expression of reporter genes in T and monocytic cell lines. The CD4-specific
      regulatory elements were included to enhance expression in CD4 cells, and viral
      regulatory regions, including the cytomegalovirus immediate-early (CMV IE)
      upstream enhancer, which contains the kappa B and Ap1 regulatory elements and a
      Tat-responsive element of the HIV type 1 long terminal repeat, were used to
      increase gene expression and modulate its activity in response to viral
      infection. In transient transfection assays, this vector was 100- to 1,000-fold
      more active than the original CD4 regulatory elements alone. Expression of an
      inhibitory form of the Rev protein, Rev M10, was more effective than previously
      described vectors and protected against productive viral replication in CD4+
      peripheral blood mononuclear cells. The combination of CD4 lineage-specific and
      viral regulatory elements will facilitate the development of more effective
      antiviral genetic strategies for AIDS.

PMID- 9261434
TI  - Herpes simplex virus genome replication and transcription during induced
      reactivation in the rabbit eye.
AB  - PCR analysis of herpes simplex virus (HSV) genome replication and productive
      cycle transcription was used to examine the role of the cornea in the latency
      associated transcript (LAT)-mediated reactivation of HSV type 1 (HSV-1) in the
      rabbit eye model. The reduced relative reactivation frequency of 17 delta Pst (a
      LAT- virus) compared to those of wild-type and LAT+ rescuants correlated with
      reduced levels of viral DNA and transcription in the cornea following epinephrine
      induction. The timing of virus appearance in the cornea was most consistent with
      tissue peripheral to the cornea itself mediating a LAT-sensitive step in the
      reactivation process. Specific results include the following. (i) While viral DNA
      was found in the corneas of rabbits latently infected with either the LAT+ or LAT
      virus prior to and during the first 16 to 24 h following induction, more was
      found in animals infected with the LAT+ virus. (ii) A significant increase in
      levels of viral DNA occurred 20 to 168 h following induction. (iii) The average
      relative amount of viral DNA was lower at all time points following reactivation
      of animals infected with the LAT- virus. (iv) Expression of productive-cycle
      transcripts could be detected in corneas of some rabbits latently infected with
      either the LAT+ or LAT- virus, and the amount recovered and the timing of
      appearance differed during the reactivation of rabbits latently infected with the
      LAT+ or LAT- virus. (v) Despite the reduced recoveries of LAT- virus DNA and
      productive-cycle transcripts in reactivating corneas in vivo compared to those of
      their LAT+ counterparts, such differences were not detected in cultured
      keratinocytes or in experiments in which relatively high titers of virus were
      superinfected into the eyes of latently infected rabbits. (vi) A number of LAT(+)
      virus-infected rabbits expressed LAT in corneas isolated from uninduced rabbits.
      When seen, its amount was significantly higher than that of a productive-cycle
      (VP5) transcript.

PMID- 9261433
TI  - The protease and the assembly protein of Kaposi's sarcoma-associated herpesvirus
      (human herpesvirus 8).
AB  - A genomic clone encoding the protease (Pr) and the assembly protein (AP) of
      Kaposi's sarcoma-associated herpesvirus (KSHV) (also called human herpesvirus 8)
      has been isolated and sequenced. As with other herpesviruses, the Pr and AP
      coding regions are present within a single long open reading frame. The mature
      KSHV Pr and AP polypeptides are predicted to contain 230 and 283 residues,
      respectively. The amino acid sequence of KSHV Pr has 56% identity with that of
      herpesvirus salmiri, the most similar virus by phylogenetic comparison. Pr is
      expressed in infected human cells as a late viral gene product, as suggested by
      RNA analysis of KSHV-infected BCBL-1 cells. Expression of the Pr domain in
      Escherichia coli yields an enzymatically active species, as determined by
      cleavage of synthetic peptide substrates, while an active-site mutant of this
      same domain yields minimal proteolytic activity. Sequence comparisons with human
      cytomegalovirus (HCMV) Pr permitted the identification of the catalytic residues,
      Ser114, His46, and His134, based on the known structure of the HCMV enzyme. The
      amino acid sequences of the release site of KSHV Pr (Tyr-Leu-Lys-Ala*Ser-Leu-Ile
      Pro) and the maturation site (Arg-Leu-Glu-Ala*Ser-Ser-Arg-Ser) show that the
      extended substrate binding pocket differs from that of other members of the
      family. The conservation of amino acids known to be involved in the dimer
      interface region of HCMV Pr suggests that KSHV Pr assembles in a similar fashion.
      These features of the viral protease provide opportunities to develop specific
      inhibitors of its enzymatic activity.

PMID- 9261435
TI  - The UL84 protein of human cytomegalovirus acts as a transdominant inhibitor of
      immediate-early-mediated transactivation that is able to prevent viral
      replication.
AB  - The 86-kilodalton immediate-early (IE) 2 protein (IE2-p86) of human
      cytomegalovirus (HCMV) is a multifunctional regulator of HCMV gene expression
      which appears to be essential for triggering the lytic replicative cycle. IE2-p86
      functions as a promiscuous transactivator of both viral and cellular gene
      expression and can repress transcription from its own promoter. In this study we
      demonstrate that a viral early protein, termed pUL84, which is able to interact
      with IE2-p86 both in vivo and in vitro, modulates IE2-p86 in a specific manner.
      First, pUL84 acts as a transdominant inhibitor of IE2-p86-mediated
      transactivation of both homologous and heterologous promoters. Second, negative
      autoregulation by IE2-p86 is augmented in the presence of pUL84. Using two in
      vivo assays, we obtained evidence that expression of pUL84 during the IE phase of
      the viral replicative cycle leads to an inhibition of viral early gene expression
      which prevents replication of HCMV and results in a persistent infection of UL84
      positive cell lines. Transdominant inhibition of a viral IE function by a protein
      expressed during the later phases of replication appears to be a novel principle
      used by herpesviruses which could account for the slow replication of HCMV and
      may be useful in the development of new antiviral strategies.

PMID- 9261436
TI  - Infectious particles derived from Semliki Forest virus vectors encoding murine
      leukemia virus envelopes.
AB  - Semliki Forest virus vectors encoding murine leukemia virus (MLV) envelope
      protein with a truncated cytoplasmic tail generate submicrometer, cell
      associated, membranous particles that transmit replication-competent vector RNA
      specifically to cells bearing the MLV receptor. Such "minimal" viruses could have
      applications as retroviral vaccines or in the study of virus evolution.

PMID- 9261437
TI  - Induction of human papillomavirus type 18 late gene expression and genomic
      amplification in organotypic cultures from transfected DNA templates.
AB  - The genetic analysis of human papillomavirus (HPV) functions during the
      vegetative viral life cycle is dependent upon the ability to generate human
      keratinocyte cell lines which maintain episomal copies of transfected viral
      genomes. We have previously demonstrated that lipofection of normal human
      foreskin keratinocytes with recircularized cloned HPV-31 genomic sequences
      resulted in a high frequency of cell lines which maintained viral genomes as
      extrachromosomal elements (M.G. Frattini, H. Lim, and L.A. Laimins, Proc. Natl.
      Acad. Sci. USA 93:3062-3067, 1996). Following the growth of these cell lines in
      organotypic (raft) cultures, the differentiation-dependent expression of viral
      late genes, the amplification of viral genomes, and virion biosynthesis were
      observed. In the present study, we demonstrate that these methodologies are not
      restricted to HPV-31 but are applicable to other HPV types, including the
      oncogenic HPV-18. HPV-18 genomes were purified from bacterial vector sequences,
      religated, and transfected into normal human foreskin keratinocytes together with
      a neomycin-selectable marker. Following drug selection, resistant cells were
      expanded and examined for the state of the viral DNA. All cell lines examined
      were found to contain approximately 100 to 200 episomal copies of HPV-18 DNA per
      cell. Growth of these cell lines in raft cultures resulted in the differentiation
      dependent expression of the E1 [symbol: see text] E4 and L1 capsid genes. In
      addition, viral genome amplification was observed in suprabasal cells following
      DNA in situ hybridization analysis of differentiated raft cultures. The induction
      of these late viral functions has previously been shown to be directly associated
      with differentiation-dependent virion biosynthesis. Our studies indicate the
      ability to perform a detailed genetic analysis of the various phases of the viral
      life cycle, including control of the differentiation-dependent late viral
      functions, using a second oncogenic HPV type.

PMID- 9261438
TI  - Varicella-zoster virus open reading frame 4 encodes an immediate-early protein
      with posttranscriptional regulatory properties.
AB  - Varicella-zoster virus (VZV) encodes four putative immediate-early proteins based
      on sequence homology with herpes simplex virus type 1: the products of ORF4, -61,
      -62, and -63. Until now, only two VZV proteins have been described as being truly
      expressed with immediate-early kinetics (IE62 and IE63). The ORF4-encoded protein
      can stimulate gene expression either alone or in synergy with the major
      regulatory protein IE62. Making use of a sequential combination of transcription
      and protein synthesis inhibitors (actinomycin D and cycloheximide, respectively),
      we demonstrated the immediate-early nature of the ORF4 gene product, which can
      thus be named IE4. The fact that IE4 is expressed with kinetics similar to that
      of IE62 further underlines the possible cooperation between these two VZV
      proteins in gene expression. Analysis of the IE4-mediated autologous or
      heterologous viral gene expression at the mRNA levels clearly indicated that IE4
      may have several mechanisms of action. Activation of the two VZV genes tested
      could occur partly by a posttranscriptional mechanism, since increases in
      chloramphenicol acetyltransferase (CAT) mRNA levels do not account for the
      stimulation of CAT activity. On the other hand, stimulation of the human
      immunodeficiency virus type 1 long terminal repeat- or the cytomegalovirus
      promoter-associated CAT activity is correlated with an increase in the
      corresponding CAT mRNA.

PMID- 9261439
TI  - The relationship between tumor necrosis factor and human immunodeficiency virus
      gene expression in lymphoid tissue.
AB  - In tissue culture models of chronic human immunodeficiency virus type 1 (HIV-1)
      infection, cytokines such as tumor necrosis factor alpha (TNF-alpha) activate
      viral gene expression. We sought evidence that TNF-alpha might similarly regulate
      viral gene expression in vivo in the major lymphoid tissue (LT) reservoir. We
      used in situ hybridization, quantitative image analysis, and double-label
      techniques to compare cytokine and HIV-1 RNA levels in sections of tonsil and
      lymph node tissues obtained from individuals in early and later stages of HIV-1
      infection. The levels of TNF-alpha gene expression in LT from HIV-1-infected an
      uninfected individuals were indistinguishable, and we found no correlation
      between TNF-alpha gene expression in LT and the level of HIV-1 gene expression in
      LT. There is thus little evidence that in vivo TNF-alpha significantly influences
      HIV production in LT.

PMID- 9261440
TI  - Transmissible Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in
      saliva of men with a history of Kaposi's sarcoma.
AB  - We have evaluated the physical state and infectious nature of Kaposi's sarcoma
      associated herpesvirus (KSHV) in the saliva of nine persons with past or current
      Kaposi's sarcoma (KS). KSHV DNA in saliva had the physical characteristics of DNA
      present in virions. Inoculation of 293 cells with cell-free saliva fluid resulted
      in the persistence of KSHV DNA in culture for at least 13 passages of the cells.
      The addition of tetradecanoyl phorbol acetate to KSHV-infected 293 cells led to
      increased viral DNA. Two virus-specific RNAs were detected by reverse
      transcriptase PCR in 293 cells infected with cell-free saliva fluid and in cells
      present in saliva from subjects with KSHV salivary shedding. These results
      indicate that infectious KSHV can be present in saliva of patients with KS.

PMID- 9261441
TI  - The rapid spread of recombinants during a natural in vitro infection with two
      human immunodeficiency virus type 1 strains.
AB  - We quantified a population of recombinants in a natural in vitro infection, using
      wild-type viruses without any pressure. It was found that recombinants emerged
      early after infection and constituted more than 20% of the whole proviral
      population 15 days after infection. Furthermore, recombinants were isolated as
      infectious viruses by simple limiting dilution. These results imply that, in
      addition to the high mutation rate of human immunodeficiency virus type 1 (HIV
      1), recombination among HIV-1 strains plays a significant part in the development
      of the high diversity of HIV-1.

PMID- 9261443
TI  - Murine CXCR-4 is a functional coreceptor for T-cell-tropic and dual-tropic
      strains of human immunodeficiency virus type 1.
AB  - The human chemokine receptor hCXCR-4 serves as a coreceptor for T-cell-tropic (T
      tropic) and dual-tropic strains of human immunodeficiency virus type 1 (HIV-1).
      We have isolated a homolog of hCXCR-4 from a murine T-cell cDNA library and have
      examined its ability to function as an HIV-1 coreceptor. mCXCR-4 was found to be
      91% identical to the human receptor at the amino acid level, with sequence
      differences concentrated in extracellular domains. Surprisingly, coexpression of
      both hCD4 and mCXCR-4 on either simian or murine cell lines rendered them
      permissive for HIV-1-induced cell fusion, indicating that mCXCR-4 is a functional
      HIV-1 coreceptor. As with hCXCR-4, coreceptor function was restricted to T-tropic
      and dual-tropic HIV-1 strains. Ribonuclease protection analysis indicated that
      mCXCR-4 mRNA was expressed in only two of six murine cell lines tested. In
      contrast, Northern blot analysis of human and mouse tissues revealed that CXCR-4
      is widely expressed in both species in vivo. Overall, these data suggest that the
      reported lack of susceptibility of hCD4+ murine cells to HIV-1 infection in vitro
      is, at least in part, due to a lack of mCXCR-4 expression rather than a lack of
      coreceptor function.

PMID- 9261442
TI  - Enhanced downregulation of Lck-mediated signal transduction by a Y114 mutation of
      herpesvirus Saimiri tip.
AB  - Tip of herpesvirus saimiri associates with Lck and downregulates Lck function in
      cellular signal transduction. In this report, we demonstrate that mutation of
      tyrosine 114 of Tip significantly increases Lck-binding activity. This mutant
      exhibits a dramatic increase in the suppression of cellular tyrosine
      phosphorylation and surface expression of lymphocyte antigens in comparison with
      wild-type Tip. In addition, the expression of TipY114 converted the transforming
      morphology of fibroblasts induced by oncogenic F505 Lck to a normal cellular
      morphology. These results further support a mechanism by which the association of
      Tip with Lck negatively regulates Lck-mediated signal transduction.

PMID- 9261444
TI  - Immunization with plasmid DNA encoding hepatitis C virus envelope E2 antigenic
      domains induces antibodies whose immune reactivity is linked to the injection
      mode.
AB  - Plasmids expressing different domains of the hepatis C virus (HCV) envelope E2
      glycoprotein from a genotype 1a isolate were constructed to compare the
      immunogenic potential of E2 in nucleic acid-based immunizations. One plasmid,
      pCIE2t, expressed a C-terminally truncated form of E2, while others, pS2.SE2A to
      pS2.SE2E, encoded the adjacent 60-amino-acid (aa) sequences of E2 (inserts A to
      E) expressed as a fusion with the hepatitis B virus surface antigen. BALB/c mice
      were given injections of the plasmids intramuscularly (i.m.) or intraepidermally
      (i.e.) via a gene gun (biolistic introduction), and induced humoral immune
      responses were evaluated. The i.e. injections resulted in higher seroconversion
      rates and antibody titers, up to 100-fold, than did the i.m. injections (P = 0.01
      to 0.04). Three restricted immunogenic domains, E2A (aa 384 to 443), E2C (aa 504
      to 555), and E2E (aa 609 to 674), that yielded antibody titers ranging from 1:59
      to > 1:43,700 could be identified. Subtype 1a- and 1b-derived E2 antigens and
      synthetic peptides were used in Western blot and enzyme-linked immunosorbent
      assay analyses, which revealed that the cross-reactivity of the plasmid-induced
      antibodies was linked both to the type of antigen expressed and to the injection
      mode. Induced anti-E2 antibodies could immunoprecipitate noncovalent E1E2
      complexes believed to exist on the surface of HCV virions. This study allowed us
      to identify restricted immunogenic domains within E2 and demonstrated that
      different routes of injection of HCV E2 plasmids can result in quantitatively and
      qualitatively different humoral immune responses.

PMID- 9261445
TI  - Active-site residues of cyclophilin A are crucial for its incorporation into
      human immunodeficiency virus type 1 virions.
AB  - Human immunodeficiency virus type 1 (HIV-1) incorporates the cellular peptidyl
      prolyl cis-trans isomerase cyclophilin A (CyPA), the cytosolic receptor for the
      immunosuppressant cyclosporin A (CsA). CsA inhibits the incorporation of CyPA and
      reduces HIV-1 virion infectivity but is inactive against closely related primate
      lentiviruses that do not interact with CyPA. The incorporation of CyPA into HIV-1
      virions is mediated by a specific interaction with a proline-containing, solvent
      exposed loop in the capsid (CA) domain of the Gag polyprotein. CsA, which
      disrupts the interaction with CA, binds at the active site of CyPA. To test
      whether active-site residues are also involved in the interaction with HIV-1 CA,
      we used a panel of previously characterized active-site mutants of human CyPA.
      Expression vectors for epitope-tagged wild-type and mutant CyPA were transfected
      into COS-gamma cells along with HIV-1 proviral DNA, and the virions produced were
      analyzed for the presence of tagged proteins. Cotransfection of the wild-type
      expression vector led to the incorporation of readily detectable amounts of
      epitope-tagged CyPA into HIV-1 virions. One CyPA mutant with a substantially
      decreased sensitivity to CsA was incorporated with wild-type efficiency,
      demonstrating that the requirements for binding to CsA and to HIV-1 CA are not
      identical. The remaining six CyPA mutants were incorporated with markedly reduced
      efficiency, providing in vivo evidence that HIV-1 CA interacts with the active
      site of CyPA.

PMID- 9261446
TI  - Expression and characterization of recombinant murine cytomegalovirus protease.
AB  - The protease domain of the murine cytomegalovirus (MCMV) M80 open reading frame
      was expressed in and purified from Escherichia coli. The recombinant enzyme was
      recovered as a mixture of active one- and two-chain forms. The two-chain enzyme
      was formed by internal cleavage of the one-chain enzyme at the I site. Activity
      measurements showed that MCMV protease cleaves R- and M-site peptide mimics with
      kinetics similar to those of recombinant human cytomegalovirus (HCMV) protease.
      Both the MCMV and HCMV proteases cleave I-site peptide substrates very poorly,
      but the crystal structure of the HCMV protease indicates that the cytomegalovirus
      I site likely resides on a solvent-exposed loop close to the active site.

PMID- 9261447
TI  - Superinfection exclusion of alphaviruses in three mosquito cell lines
      persistently infected with Sindbis virus.
AB  - Three Aedes albopictus (mosquito) cell lines persistently infected with Sindbis
      virus excluded the replication of both homologous (various strains of Sindbis)
      and heterologous (Aura, Semliki Forest, and Ross River) alphaviruses. In
      contrast, an unrelated flavivirus, yellow fever virus, replicated equally well in
      uninfected and persistently infected cells of each line. Sindbis virus and
      Semliki Forest virus are among the most distantly related alphaviruses, and our
      results thus indicate that mosquito cells persistently infected with Sindbis
      virus are broadly able to exclude other alphaviruses but that exclusion is
      restricted to members of the alphavirus genus. Superinfection exclusion occurred
      to the same extent in three biologically distinct cell clones, indicating that
      the expression of superinfection exclusion is conserved among A. albopictus cell
      types. Superinfection of persistently infected C7-10 cells, which show a severe
      cytopathic effect during primary Sindbis virus infection, by homologous virus
      does not produce cytopathology, consistent with the idea that cytopathology
      requires significant levels of viral replication. A possible model for the
      molecular basis of superinfection exclusion, which suggests a central role for
      the alphavirus trans-acting protease that processes the nonstructural proteins,
      is discussed in light of these results.

PMID- 9261448
TI  - Chemokine receptor CCR5 genotype influences the kinetics of human
      immunodeficiency virus type 1 infection in human PBL-SCID mice.
AB  - Individuals homozygous for a 32-bp deletion (delta 32) in the CCR5 gene encoding
      the coreceptor for macrophage-tropic human immunodeficiency virus type 1 (HIV-1)
      are resistant to virus infection, and heterozygous individuals show some slowing
      of disease progression. The impact of the CCR5 genotype on HIV-1 infection was
      assessed in vitro and in the human PBL-SCID (hu-PBL-SCID) model. Cells and hu-PBL
      SCID mice from CCR5 delta 32/delta 32 donors were resistant to infection with
      macrophage-tropic HIV-1 and showed slower replication of dual-tropic HIV-1. hu
      PBL-SCID mice derived from CCR5 delta 32/+ heterozygotes showed delayed
      replication of macrophage-tropic HIV-1 despite a small and variable effect of
      heterozygosity on viral replication in vitro. The level of CCR5 expression
      appears to limit replication of macrophage-tropic and dual-tropic HIV-1 strains
      in vivo.

PMID- 9261449
TI  - A conditional self-inactivating retrovirus vector that uses a tetracycline
      responsive expression system.
AB  - We developed a novel conditional self-inactivating (C-SIN) vector, TL-SN, by
      replacement of the enhancer-promoter of the 3' long terminal repeat of Moloney
      murine leukemia virus with a synthetic tetracycline operator-cytomegalovirus
      promoter (tetP) from the tetracycline-responsive expression system (TRES). The
      other component of the TRES, a chimeric transactivator (tTA), was stably
      incorporated into PA317 amphotropic packaging cells, thus generating the
      packaging cell line PA317-tTA. C-SIN amphotropic G418-resistant virus particles
      were generated with a titer of 2 x 10(5) CFU/ml within 2 days of transinfection
      of PA317-tTA cells with TL-SN ecotropic virus particles. This titer was
      approximately 2 log units higher than that obtained by transinfection of parental
      PA317 cells and was due to the high level of viral transcripts originating from
      the tetP promoter at the 5' end of the transduced vector in the presence of tTA.
      Our C-SIN vector has the potential for use in human gene therapy since it
      incorporates the advantages of previous SIN vectors in having weak tetP promoter
      activity (in the absence of tTA in target cells) while at the same time achieving
      high viral titers with PA317-tTA packaging cells.

PMID- 9261450
TI  - A single amino acid substitution in the transmembrane envelope glycoprotein of
      feline immunodeficiency virus alters cellular tropism.
AB  - The cellular tropism of the feline immunodeficiency virus (FIV) is affected by
      changes in variable region 3 (V3) of the surface (SU) envelope glycoprotein
      (Verschoor, E. J., et al., J. Virol. 69:4752-4757, 1995). By using high-dose DNA
      transfection, an FIV molecular clone with a non-CRFK-tropic V3 acquired the
      ability to replicate in CRFK cells. A single point mutation from a methionine to
      a threonine in the ectodomain of its transmembrane (TM) envelope glycoprotein was
      responsible for this change in viral tropism. This substitution is located in the
      putative SU interactive region, between the fusion peptide and the membrane
      spanning region. Our results show that this region of the TM envelope
      glycoprotein constitutes an additional determinant for cell tropism.

PMID- 9261452
TI  - Potentiation of human immunodeficiency virus type 1 Tat by human cellular
      proteins.
AB  - The Tat protein is a potent activator of human immunodeficiency virus type 1
      transcription. Tat has been shown to act by increasing both transcription
      initiation and elongation, but a detailed understanding of its interaction with
      the transcriptional machinery is lacking. With the aim of isolating cellular
      proteins that interact with Tat and play a role in transactivation, we have
      reexamined its function in a cell-free transcription assay. Monitoring the
      appearance of transactivation after addition of purified Tat at intervals to the
      reaction mix revealed a lag of approximately 10 min before Tat is able to effect
      transactivation. Incubation of Tat in nuclear or cytoplasmic extracts of human
      cells was sufficient to eliminate the lag, but nuclear extract from a rodent cell
      line was inactive. The accelerating effect of the human cell extract could be
      abrogated by dilution, heat inactivation, or chromatographic depletion. We infer
      that Tat is potentiated for transactivation through interaction with a protein
      factor(s) that is specific to human cells.

PMID- 9261451
TI  - Selective employment of chemokine receptors as human immunodeficiency virus type
      1 coreceptors determined by individual amino acids within the envelope V3 loop.
AB  - The chemokine receptor CCR5 acts as an essential cofactor for cell entry by
      macrophage-tropic human immunodeficiency virus type 1 (HIV-1) strains, whereas
      CXCR4 acts as an essential cofactor for T-cell-line-adapted strains. We
      demonstrated that the specific amino acids in the V3 loop of the HIV-1 envelope
      protein that determine cellular tropism also regulate chemokine coreceptor
      preference for cell entry by the virus. Further, a strong correlation was found
      between HIV-1 strains classified as syncytium inducing in standard assays and
      those using CXCR4 as a coreceptor. These data support the hypothesis that
      progressive adaptation to additional coreceptors is a key molecular basis for HIV
      1 phenotypic evolution in vivo.

PMID- 9261454
TI  - Evaluation of an automatic-mode image processing method in chest computed
      radiography.
AB  - RATIONALE AND OBJECTIVES: The automatic image processing mode of the storage
      phosphor computed radiography system was evaluated. MATERIALS AND METHODS: A
      dedicated chest unit designed for erect view was used to examine a chest phantom.
      Lucite plates 1, 2, and 3 cm thick that conformed to the shape of the lung were
      attached to the phantom, and images were obtained in automatic and manual image
      processing modes. The changes in the optical density of the lung, rib, and heart
      and the changes in contrast were measured. The degree of diffuse opacity due to
      the plates and the visibility of superimposed simulated nodular and honeycomb
      opacities were evaluated. RESULTS: The decrease in optical density and contrast
      caused by increasing thickness of the Lucite plates was less pronounced in the
      automatic mode compared with the manual mode. When plates were placed only on the
      right lung, the optical density and the contrast on the contralateral side either
      increased or remained unchanged with the automatic mode. The degree of diffuse
      opacity was rated higher in the manual mode, and the visibility of superimposed
      simulated opacities was considered relatively constant in the automatic mode.
      CONCLUSION: The automatic image reading mode used in the computed radiography
      chest system may mask the detection of abnormalities such as diffuse homogeneous
      lung opacity.

PMID- 9261453
TI  - Reduction of patient exposure in pediatric radiology.
AB  - RATIONALE AND OBJECTIVES: The authors determined whether presently used exposure
      levels in pediatric imaging can be reduced without loss of information or a
      decrease in diagnostic accuracy. MATERIALS AND METHODS: Multiple (stacked) image
      detectors and filters were used to obtain identical compute radiographic images
      at different exposure levels of neonates with either no active lung disease or
      hyaline membrane disease. Physical characteristics of the images were measured. A
      contrast-detail study and a receiver operating characteristic study were
      conducted to measure observer performance. RESULTS: Physical measurements and
      results of the contrast-detail study revealed that the dose-reduction images were
      essentially limited by x-ray quantum noise. Results of the receiver operating
      characteristic study indicated that diagnostic accuracy did not decrease
      significantly up to about 75% exposure reduction levels, although image quality
      rating data decreased with each exposure reduction. CONCLUSION: Decreasing
      exposure levels to about 75% of current levels may be acceptable in some clinical
      situations where dose is a concern, such as in pediatric imaging.

PMID- 9261455
TI  - Evaluation of a turkey-breast phantom for teaching freehand, US-guided core
      needle breast biopsy.
AB  - RATIONALE AND OBJECTIVES: Use of a turkey-breast phantom for developing freehand
      ultrasound (US)-guided core-needle biopsy skills was evaluated. MATERIALS AND
      METHODS: Thirteen diagnostic radiology trainees with varied experience in
      freehand US-guided breast core-needle biopsy were given instruction and allowed
      to practice the technique in a turkey-breast phantom. Three attempts were made
      before and after instruction and practice, and a questionnaire regarding
      experience, confidence, and anxiety was administered after these attempts.
      Technique, accuracy, and completion time were evaluated. RESULTS: Confidence
      related to procedure performance increased (P < .01), but the change in anxiety
      was not statistically significant. Accuracy improved, with the target being
      obtained in 87% of passes performed after instruction and practice versus 56%
      initially. Difficulty with visualizing the core needle sonographically during
      phantom biopsy decreased from 49% to 5% of attempts. Needle positioning
      perpendicular to the chest wall was observed initially in 38% of passes but was
      not observed after instruction and practice. There was no statistically
      significant change in time to complete biopsy. CONCLUSION: For teaching US-guided
      breast core-needle biopsy, use of a turkey-breast phantom helps improve
      technique, accuracy, and confidence of diagnostic radiology trainees.

PMID- 9261456
TI  - Comparison of conventional and computed radiography: assessment of image quality
      and reader performance in skeletal extremity trauma.
AB  - RATIONALE AND OBJECTIVES: Reader performance and image quality wee assessed for
      standard film, computed film, and computer monitor radiography viewing formats in
      the evaluation of skeletal extremity trauma. MATERIALS AND METHODS: Three
      radiologists and three orthopedic surgeons interpreted 27 skeletal radiographs
      obtained with equivalent technical parameters. Readers evaluated standard film,
      computed film, and computer monitor formats randomly for fracture and soft-tissue
      abnormalities. Sessions were videotaped, and eye motion was recorded. RESULTS: No
      statistically significant differences were found between image formats for true
      positive or false-positive findings of trauma indicators. Findings were
      classified as false-negative based on eye position fixation times. Search errors
      (lesion not fixated) accounted for 21.7%, 20.6% and 17.1% of false-negative
      errors with the computer monitor, computed film, and standard film formats,
      respectively. Combined recognition errors and decision errors were 78.3%, 79.4%,
      and 82.9%, respectively. Viewing times were longest for the computer monitor
      images (P < .001). Image quality, contrast, and sharpness were rated highest for
      computed radiographs (P = .001). Radiologists had a higher true-positive decision
      rate than orthopedic surgeons (P = .03). CONCLUSION: No statistically significant
      differences were seen in reader performance among viewing formats. The computed
      film format received the highest quality rating, and workstation viewing times
      were longest.

PMID- 9261457
TI  - Use of intravenous contrast material in transcranial sonography.
AB  - RATIONALE AND OBJECTIVES: The appearance of the intracranial vasculature was
      compared on power and color Doppler ultrasound (US) scans obtained with and
      without a microbubble contrast agent. MATERIALS AND METHODS: Nine patients (three
      men, six women) aged 42-70 years (mean age, 53 years) participated in the study.
      Seven patients underwent both color Doppler US and power Doppler US before and
      after intravenous administration of contrast agent, and two underwent only color
      Doppler US. All patients had previously undergone cerebral angiography. RESULTS:
      Before contrast material was administered, power Doppler US was more sensitive
      than color Doppler US in the detection of intracranial vessels (P < .05); neither
      technique depicted the entire circle of Willis in eight of nine patients.
      Postcontrast power Doppler US depicted more vascular segments than postcontrast
      color Doppler US (P < .01) or precontrast power Doppler US (P < .01). Use of
      intravenous contrast material enabled the entire circle of Willis to be evaluated
      from a single temporal bone acoustic window with both power Doppler US and color
      Doppler US in all patients. Contrast-enhanced power Doppler US depicted vessels
      not shown by enhanced color Doppler US. CONCLUSION: Contrast-enhanced power
      Doppler US depicted more vessels, better demonstrated specific vascular segments,
      and provided better vascular definition of the intracranial vasculature than
      contrast-enhanced color Doppler US or unenhanced power Doppler US.

PMID- 9261458
TI  - Virtual bronchoscopy with perfluoronated hydrocarbon enhancement.
AB  - RATIONALE AND OBJECTIVES: Bronchoscopic computed tomography (CT) is limited by
      machine resolution and air-soft-tissue contrast. The objective of this study was
      to determine whether improving the contrast by using the contrast agent
      perflubron (PFOB) in the lung would improve the bronchoscopic CT technique and
      permit visualization of small airways. MATERIALS AND METHODS: Bronchoscopic CT
      was performed in an anesthetized 8-week-old New Zealand white rabbit before and
      after the endotracheal administration of PFOB. RESULTS: Bronchoscopic CT
      performed with PFOB permitted navigation of bronchi as small as 0.8 mm in
      diameter, which are much smaller than those that can be navigated without PFOB.
      CONCLUSION: In this example, the use of perfluorochemicals with bronchoscopic CT
      enhanced the capabilities of virtual bronchoscopy.

PMID- 9261459
TI  - Variance-component modeling in the analysis of receiver operating characteristic
      index estimates.
AB  - RATIONALE AND OBJECTIVES: The authors performed this study to clarify and
      systematize the large number of variances and correlations observable with
      variance-component models of receiver operating characteristic (ROC) index
      estimates. MATERIALS AND METHODS: The authors present a variance-component model
      for ROC index estimates (and for differences between estimates) and show
      correspondences between the method of experimental replication and the random
      components in the model. The authors introduce a notation that identifies both
      the method of replication and, when examining estimate differences, the estimate
      pairing scheme. RESULTS: For models with three factors (modality, reader, case
      sample), the authors delineated four methods of replication and eight pairing
      schemes for generating estimate differences. For each of the resulting 32
      replication-pairing combinations, the authors gave expressions for the variance
      of the difference and for the correlation between the two ROC index estimates.
      CONCLUSION: The variance-component approach is a useful statistical tool for
      modeling different sources of variation that contribute to the overall variance
      of ROC data and index estimates derived from those data.

PMID- 9261460
TI  - Medical students' attitudes toward radiology: comparison of matriculating and
      graduating students.
AB  - RATIONALE AND OBJECTIVES: To determine graduating medical students' perceptions
      of radiology and to document changes in their perceptions since they entered
      medical school. MATERIALS AND METHODS: A survey questionnaire was distributed to
      213 graduating students. Questions were similar to those answered by the same
      group of students as they entered medical school nearly 4 years earlier. RESULTS:
      The survey was anonymously completed by 140 students. Seventy percent of students
      changed their choice of medical specialty since entering medical school. Factors
      with a major or important influence on specialty choice included intellectual
      excitement (96%), high patient contact (86%), opportunity for a good family life
      (72%), and regular hours (57%). Radiology was perceived to be a well-paid (89%),
      "high-tech" (86%) specialty with a healthy lifestyle (82%), regular hours (99%),
      and good family life (92%), but it was not perceived to offer high patient
      contact (1%) and was intellectually exciting to only 33% of students. This
      perception was unchanged from freshman year. CONCLUSIONS: This 4-year
      longitudinal study of a medical student class documents surprisingly little
      change in the perception of radiology throughout medical school. High patient
      contact and intellectual excitement, both factors of major or important influence
      on specialty choice, were thought to be lacking in radiology.

PMID- 9261461
TI  - Right iliac fossa pain.

PMID- 9261462
TI  - Choosing an academic career.

PMID- 9261463
TI  - Measurement of inotropic effects by a newly developed guinea pig papillary muscle
      bioassay.
AB  - In order to measure inotropic influences of physiologically occurring substances
      and drugs we used a newly developed guinea pig papillary muscle (GPPM) bioassay.
      GPPM were suspended in air and surface coated with buffer (Krebs-Henseleit
      solution). The muscles were stimulated (pulsating direct current, 1.5 V; 0.5 Hz,
      20 ms duration) which led to contraction. This method enables measurements of
      inotropic effects up to 5 days, contrary to previous studies (1 day), in which
      immersions of GPPM in buffer were performed. In order to investigate the
      comparability of the new method we measured the effect of metabolites (citric
      acid cycle), lactic acid, lactate, and extracellular pH on muscle contractility.
      The H(+)-dependent decrease of the contractile force of the GPPM can be
      compensated by an increased Ca(2+)-concentration. Further, the influence of
      catecholamines (isoproterenol) on the contractility was investigated. As a
      result, isoproterenol caused arrhythmias and extrasystoles as it was observed in
      clinical studies. Several pharmaceutical substances were tested to show the
      reproducibility and repeatability of the bioassay.

PMID- 9261464
TI  - Sleep apnea and cognitive dysfunction in myasthenia gravis.
AB  - 19 middle-aged patients with myasthenia gravis (MG) and 10 age, sex and education
      matched controls underwent overnight polysomnography and neuropsychological
      testing, in order to test the hypothesis of whether cognitive dysfunction and REM
      sleep disturbance in MG are related to nocturnal respiratory problems or caused
      by CNS-involvement. We observed in 60% of the myasthenics central type of sleep
      apneas and hypopneas with resulting oxygen desaturations occurring during REM
      sleep, but no decrease of REM sleep. In neuropsychological testing, we found
      normal vigilance performance but decreased memory function in the myasthenics. In
      comparison with patients without sleep apnea, myasthenics with sleep apneas had
      an impaired memory function.

PMID- 9261465
TI  - On Japanese baseball and erythema induratum of Bazin.

PMID- 9261467
TI  - Fetal and adult hair follicle. An immunohistochemical study of anticytokeratin
      antibodies in formalin-fixed and paraffin-embedded tissue.
AB  - The expression of cytokeratins (CK), involucrin, vimentin, CD34, and alpha-smooth
      muscle actin was studied in fetal and adult hair follicles. The first stage of
      the developing hair follicle is characterized by palisaded, elongated epithelial
      cells budding from the epidermal basal layer. These cells express CK5/6, CK14,
      CK17, CK19, and vimentin. During the following weeks of gestation, different
      structures in the developing hair follicle can be identified and characterized.
      The matrical cells display only CK19. The keratinocytes of the outer root sheath
      express CK5/6, CK14, CK17, CK19, and involucrin; those of the inner root sheath,
      CK4, CK18, and involucrin; those of the isthmus, the same profile as the ORS. In
      the infundibulum, the basal-layer keratinocytes express CK5/6, CK14, CK17, and
      CK19, whereas in the suprabasal layers CK1, CK4, CK10, CK14, and CK17 are seen.
      The adult hair follicle in anagen fails to express CK19 in the matrical cells and
      isthmus and both CK17 and CK19 in the infundibulum. These profiles of
      intermediate filaments and other markers appear to be potentially useful in
      categorizing neoplasms with apparent follicular differentiation.

PMID- 9261466
TI  - The histopathologic spectrum of erythema induratum of Bazin.
AB  - Erythema induratum of Bazin is a tuberculid that is strongly associated with
      tuberculosis. Clinically, erythema induratum of Bazin show recurrent tender
      subcutaneous nodules that occur mainly on the calves of women with tuberculin
      hypersensitivity. Previous studies have not documented the histopathologic
      spectrum of erythema induratum of Bazin in detail. We identified two major
      histopathologic groups in 19 of 20 skin biopsies obtained from 20 patients with
      well-documented erythema induratum of Bazin. Six cases (group I) showed focal
      septolobular panniculitis in close association with a single muscular artery or
      small vessel with primary neutrophilic vasculitis. Thirteen cases (group II)
      revealed diffuse septolobular panniculitis with primary neutrophilic vasculitis
      of either large or smaller vessels. Both groups showed varying combinations and
      degrees of acute and chronic inflammation, coagulative and caseation-like
      necrosis, and granulomatous inflammation. Poorly developed granulomas
      predominated, but mixed, palisading, and lipophagic granulomas also occurred.
      Inflammation and necrosis were more extensive in group II. Erythema induratum of
      Bazin may show predominantly acute suppurative or granulomatous panniculitis.
      Immunostaining showed S100+ antigen-presenting cells, macrophages, and T
      lymphocytes. B-lymphocytes were rare. The presence of primary vasculitis and
      granulomas suggests that types III and IV hypersensitivity reactions play a role
      in the pathogenesis or erythema induratum of Bazin. The latter remains a
      clinicopathologic diagnosis, but awareness of the heterogeneous histopathologic
      spectrum of EIB will ensure a timely diagnosis and institution of antituberculous
      treatment.

PMID- 9261468
TI  - Trichoblastoma and basal cell carcinoma are neoplasms with follicular
      differentiation sharing the same profile of cytokeratin intermediate filaments.
AB  - Trichoblastoma and nodular basal cell carcinoma are generally held to be
      distinctive epithelial neoplasms with some overlapping features. We investigated
      30 trichoblastomas in which the basaloid cells expressed cytokeratins (CK) CK5/6,
      CK14, CK17, CK19, and, in a few cells, vimentin. The cells of the periphery of
      small and large cysts showed the same profile. Cells lining the lumen of small
      cysts expressed CK14, CK17, and involucrin, and those in larger cysts showed a
      positivity for CK1, CK4, CK10, CK14, CK17, and involucrin. The remaining tested
      antibodies (CK7, CK8, CK13, CK18, CK20, alpha-smooth-muscle actin) were negative
      in all cases. The cells of the stroma expressed vimentin and in 22 cases, the
      CD34 antigen. Seventeen nodular basal cell carcinomas showed exactly the same
      staining pattern. Furthermore, there are striking immunohistochemical
      similarities between the neoplastic basaloid cells of both neoplasms and the
      cells of the hair germ. Therefore, trichoblastoma and nodular basal cell
      carcinoma cannot be distinguished by their pattern of cytokeratin expression in
      paraffin sections. The virtually identical cytokeratin pattern seen in
      trichoblastoma, basal cell carcinoma, and the developing fetal hair follicle is
      compelling evidence for common differentiation pathway.

PMID- 9261469
TI  - Clear cell hidradenoma associated with the folliculo-sebaceous-apocrine unit.
      Histologic study of five cases.
AB  - Hidradenomas are benign adnexal neoplasms of uncertain derivation. Although most
      investigators traditionally have considered these neoplasms to exhibit eccrine
      differentiation, with only occasional reports supporting apocrine derivation,
      subdivision of hidradenomas into two groups was recently suggested: those with
      eccrine differentiation (or poroid hidradenomas) and those exhibiting apocrine
      differentiation (or clear cell hidradenomas). We have observed five cases of
      clear cell hidradenomas manifesting unquestionable apocrine characteristics
      excised from sites other than the axilla, and displaying continuity with the
      epidermis through follicles. Because of the common embryologic derivation of
      apocrine glands, sebaceous glands, and hair follicles, and their histologic
      integration as the folliculo-sebaceous-apocrine unit, these findings suggest a
      possible origin of certain apocrine hidradenomas from pluripotential germinative
      cells present in follicles.

PMID- 9261470
TI  - Microcystic adnexal carcinoma with extensive sebaceous differentiation.
AB  - We report two cases of microcystic adnexal carcinoma showing extensive sebaceous
      differentiation. Multiple cellular nests and strands within a moderately
      sclerotic stroma involving the full thickness of the dermis were observed.
      Clusters of basaloid cells with extensive sebaceous differentiation were present.
      Foci of sebaceous ductal differentiation were observed in the more superficial
      areas. Neither strikingly atypical cells nor mitotic figures were present.
      Perineural invasion was present in the deep areas of both tumors. Clinically, the
      lesions were solitary whitish-pink papules with a central dell on the faces of 2
      men (aged 78 and 73 years old). We propose a relationship between these tumors
      and other cytologically bland but locally aggressive adnexal carcinomas.
      Sebaceous differentiation itself in a poorly circumscribed neoplasm does not
      indicate conventional extraocular sebaceous carcinoma. We propose a simple
      classification of locally aggressive adnexal carcinomas that takes into account
      the full range of adnexal differentiation that can occur in such lesions.

PMID- 9261471
TI  - Primary metaplastic carcinoma (carcinosarcoma) of the skin. A clinicopathologic
      study of four cases and review of the literature.
AB  - Metaplastic carcinoma (carcinosarcoma, sarcomatoid carcinoma, malignant mixed
      tumor) is a biphasic tumor comprising malignant epithelial and heterologous
      mesenchymal elements. Primary cutaneous cases are rare, with only seven cases
      documented in the English literature to date. We present four further cases,
      including three that developed in association with squamous cell carcinoma and
      one in an eccrine porocarcinoma. Heterologous malignant mesenchymal elements
      included malignant osteosarcoma, chondrosarcoma, leiomyosarcoma, and
      rhabdomyosarcomas. In contrast to metaplastic carcinomas arising in visceral
      sites, those primarily arising in the skin do not appear to behave in a very
      aggressive manner (Recurrence rate 22%, metastasis rate 22%, overall mortality
      11%). However, the numbers involved are small and the follow-up period is short.
      In view of recent developments and progress in our understanding of the possible
      histogenesis of such tumors, we suggest that metaplastic carcinoma rather than
      carcinosarcoma is the most appropriate term with which to describe these very
      rare cutaneous neoplasms.

PMID- 9261472
TI  - Expression and mutation of the tumor suppressor gene p53 in AIDS-associated
      Kaposi's sarcoma.
AB  - Alteration of the p53 gene is the most frequent event reported in human cancer,
      and p53 mutations have been observed in various neoplasms, including certain
      forms of skin cancer. Therefore, we postulated that p53 may also be involved in
      Kaposi's sarcoma associated with AIDS (AIDS-KS). Expression of the p53 gene was
      examined in freshly isolated tumor biopsy specimens from 15 patients with AIDS
      KS. p53 mRNA was detected by reverse transcriptase-polymerase chain reaction (RT
      PCR) in both the AIDS-KS tumors and in normal skin control samples. p53 protein
      was detected in 4 of the 15 AIDS-KS specimens by immunohistochemical staining.
      Single-strand conformation polymorphism analysis PCR-products (PCR-SSCP) was used
      for detection of mutations of the p53 gene. One of the p53 positive AIDS-KS
      samples showed mobilized shifts in exon 6 suggestive of a mutation. Sequencing
      data showed the mutation to be located in codon 210. We examined other mechanisms
      that could stabilize p53 protein. SV40 large T antigen and adenovirus E1B protein
      were not found in the AIDS-KS specimens. MDM2, a p53-binding protein, was also
      detected in five of the AIDS-KS specimens, two of which also contained p53
      positive cells. These observations suggest that the tumor suppressor gene p53 may
      be involved in the pathogenesis of AIDS-KS.

PMID- 9261473
TI  - Bullous lesions in Kaposi's sarcoma: case report.
AB  - Bullous lesions have been only rarely described in Kaposi's sarcoma (KS), and
      their histopathologic features have never been described in detail. We report a
      case of bullous lesions of KS in an 82-year-old Italian woman. The patient had
      typical smooth pale reddish-grey slightly-raised KS plaques on the legs, present
      for at least 10 years. Several dull grayish-pink blisters (0.5 to 2 cm in
      diameter) affected both dorsa of her feet and ankles symmetrically. Two punch
      biopsies were taken, one from an infiltrated KS plaque on the right buttock and
      the other from a bullous lesion on the right foot. Histopathologically, the late
      KS plaque on the buttock showed typical features of KS, with an increased number
      of spindle cells arranged in short bundles and extravasation of erythrocytes. The
      bullous lesion on the foot showed a full-thickness vascular neoplasm involving
      the upper and lower dermis and the subcutaneous fat. The upper portion of the
      lesion contained many newly formed, highly-dilated blood vessels, touching the
      overlying epidermis and separated from it by a narrow band of collagen and
      endothelial cells; wide, empty spaces characterized the superficial dermis, in
      which preexisting venules and bands of collagen associated with non-atypical
      endothelial cells floated. All these findings would suggest a lymphangiomatous
      lesion, if the presence of specific diagnostic criteria of KS were not
      recognizable at a deeper level of the lesion. Various criteria actually suggest
      that the bullous lesion may be regarded as an epiphenomenon of a KS plaque
      lesion: (a) full-thickness involvement of the reticular dermis and, in this case,
      also of the subcutaneous fat; (b) dense and patchy lymphoplasmocytic infiltrate
      typical of plaque lesions and, much less frequently, of patch lesions; (c)
      presence of ectatic blood vessels, filled with plasma and erythrocytes
      (pseudoangiomatous findings), a nonpathognomonic but highly characteristic
      finding of the plaque lesion; and (d) as in the KS plaque lesions, in the bullous
      lesion as well the reticular dermis was characterized by an increased number of
      anastomosing bizarrely shaped vascular spaces lined by non-atypical endothelial
      cells. We hypothesize that the prevalence of lymphangiomatous differentiation in
      the upper dermis represents one of the many features of KS lesions. When present,
      it may correlate with the clinical feature of a blister.

PMID- 9261474
TI  - CD56/neural cell adhesion molecule expression in primary extranodal Ki-1/CD30+
      lymphoma. Report of a pediatric case with simultaneous cutaneous and bone
      localizations.
AB  - We describe the clinicopathologic features of an unusual case of CD30+/CD50+ T
      cell lymphoma in a child who presented with simultaneous primary extranodal
      cutaneous and bone localizations. The expression of CD56 (neural cell adhesion
      molecule, or NCAM) is rare in non-Hodgkin's lymphomas other than in a group of
      haematopoietic/lymphoid neoplasms of natural killer and natural killer-like T
      cells, which usually involve extranodal sites and often pursue an aggressive
      clinical behavior. Coexpression of CD30 and CD56 in T-cell lymphomas is
      exceedingly rare, and its biological significance is unknown. Our patient
      responded well to an intensive chemotherapy regimen, and she is now in complete
      remission 4 years after discontinuation of chemotherapy. Expression of NCAM could
      be regarded as responsible, in part, for the extranodal localization of lymphoma
      cells; expression of CD56 also might contribute to the definition of a subset of
      CD30+ lymphomas with distinctive clinicopathologic features.

PMID- 9261475
TI  - Expression of intercellular adhesion molecule 3 (CDw50) on endothelial cells in
      cutaneous lymphomas. A comparative study between nodal and cutaneous lymphomas.
AB  - Advances in the molecular definition of surface proteins (adhesion molecules)
      involved in tumor metastasis may help to explain the invasive behavior of
      malignant tumors, that is, the migration of tumor cells involving reversible
      adhesive contacts, their release in the circulation, and their extravasation into
      distant sites. Intercellular adhesion molecule-3 (ICAM-3), the third receptor for
      the lymphocyte function-associated antigen molecule-1 (LFA-1) was recently
      characterized. We investigated fresh frozen skin biopsies from 10 patients with
      mycosis fungoides, four with pleomorphic T-cell lymphoma, six with Sezary
      syndrome, 10 with primary cutaneous B-cell lymphoma, and 10 with eczematous
      lesions as controls. The biopsies were compared with lymph node biopsies of five
      patients with known cutaneous T-cell lymphoma (CTCL), 10 with primary nodal B
      cell lymphoma, and 11 with lymph-node specimens showing dermatopathic
      lymphadenopathy as controls. The specimens were stained with ICAM-3 antibody
      (Bender Medical Science) using the alkaline phosphatase antialkaline phosphatase
      method. Using cytomorphologic criteria, neoplastic lymphocytes could be
      differentiated from smaller reactive cells. Staining intensities were classified
      semiquantitatively as follows: 4, strong expression in 75 to 100% of the tumor
      cells; 3, 50 to 75%; 2, 25 to 50%; 1, 5 to 25%; and 0 fewer than 5% of the tumor
      cells. The endothelial cells in skin biopsies of seven of 30 primary cutaneous
      lymphomas expressed ICAM-3. In contrast, no expression of ICAM-3 could be
      demonstrated on endothelial cells in lymph nodes infiltrated with tumor cells of
      CTCL. Finally, endothelial cells of lymph nodes infiltrated with primary nodal B
      cell lymphomas showed expression of ICAM-3 in three of 10 patients. The
      endothelial cells in the 11 control patients presenting with both eczematous
      lesions and dermatopathic lymphadenopathy showed no staining for ICAM-3. Every
      patient who expressed ICAM-3 on endothelial cells showed systemic spread of this
      disease. The findings suggest that ICAM-3 expression may be induced on
      endothelial cells in late-stage cutaneous lymphomas, probably by a cytokine
      mediated mechanism.

PMID- 9261476
TI  - Proliferative fasciitis. Report of a case with histopathologic and
      immunohistochemical studies.
AB  - We present a case of proliferative fasciitis arising adjacent to an operative
      scar of the right lower leg of a patient with chronic lymphatic leukemia,
      diabetes mellitus, and multiple subcutaneous angiolipomas. A 61-year old man had
      a hard mass in his right lower leg that had rapidly increased in size in the past
      10 days. The mass was microscopically composed of a dense proliferation of
      spindle cells forming interlacing fascicles admixed with an inflammatory
      infiltrate of lymphocytes and eosionphils, focal hemorrhage, and myxomatous
      change as typically seen in nodular fasciitis as well as many characteristic
      ganglion cell-like giant cells. Immunohistochemically, most of the spindle-shaped
      cells were positive for vimentin and alpha-actin, whereas the ganglion cell-like
      giant cells were positive for vimentin and negative for alpha-actin and lysozyme.
      We suggest that the main component cells of proliferative fasciitis are
      fibroblastic in nature, many of which are myofibroblasts in large part, whereas
      the ganglion cell-like giant cells are related more closely to fibroblasts rather
      than histiocytes or pericytes. Additionally, proliferating cell nuclear antigen
      (PCNA) stain revealed that many of the fibroblastic cells showed high
      proliferative activity, especially in the hypercellular areas, although there was
      no significant difference in PCNA staining between the focus traumatized by the
      needle biopsy and the nontraumatized areas.

PMID- 9261477
TI  - Analysis of the lymphocytic infiltrate in a case of vitiligo.
AB  - We report a case of vitiligo notable for a degree and pattern of lymphocytic
      inflammation. Hypopigmentation and subsequent depigmentation developed in a 65
      year-old man. Initial skin biopsy specimen from the border of a patch of
      hypopigmentation revealed a moderately dense perivascular and interstitial
      infiltrate of lymphocytes with exocytosis into epidermis and follicular
      epithelium. The pattern of the infiltrate suggested the diagnosis of cutaneous T
      cell lymphoma or connective-tissue disease. Immunophenotypic analysis revealed a
      mature T-cell population with retention of pan-T-cell markers. Analysis of the T
      cell receptor genome did not identify a rearranged clone. Six months later, the
      clinical and histologic findings were typical in a noninflamed lesion of
      vitiligo.

PMID- 9261478
TI  - Neutrophilic figurate erythema of infancy.
AB  - We describe a transient figurate erythema in an 11-month-old female infant with a
      2-month history of arcuate and annular erythematous lesions localized on the
      face, trunk, and limbs. Constitutional symptoms were absent. Previous medical
      history was unremarkable. Full blood examination, erythrocyte sedimentation rate,
      antistreptolysin-O titer, anti-Ro, and anti-La antibodies were within normal
      limits or negative. Histologic examination revealed a superficial and deep
      perivascular and interstitial dermatitis constituted mostly of neutrophils and
      abundant nuclear dust. The lesions resolved spontaneously within a few months
      without scarring or atrophy. Recurrence has not occurred. This case suggests that
      figurate erythemas in infants rarely may disclose a neutrophilic histologic
      pattern, which must be differentiated from that of other neutrophilic dermatoses.

PMID- 9261479
TI  - Cutaneous metaplastic synovial cyst in an Ehlers-Danlos patient.
AB  - Metaplastic synovial cyst is a recently reorganized entity characterized by a
      cystic space lined by polygonal cells and villous structures resembling synovium
      pointing toward the lumen. It usually develops following trauma. We report a 15
      year-old girl with Ehlers-Danlos syndrome who developed a nodular lesion of her
      elbow without previous trauma. Histopathological and immunohistochemical studies
      yielded results similar to those reported in cases of cutaneous metaplastic
      synovial cyst. This case appears to be the first one reported of cutaneous
      metaplastic synovial cyst associated with an Ehlers-Danlos syndrome. Cutaneous
      fragility and anomalous scarring typical of Ehlers-Danlos syndrome may be related
      to the development of this pseudocyst. If so, other connective-tissue diseases
      with increased skin fragility could be susceptible to development of such
      lesions.

PMID- 9261480
TI  - Histopathologic findings in drug-induced pemphigus.
AB  - Drug-induced pemphigus represents a diagnostic challenge, as usually no clinical
      feature differentiates it from its idiopathic counterpart. It was suggested
      recently that some histologic features may assist in diagnosing drug-associated
      diseases. The purpose of the study was to determine whether the histologic
      criteria suggested in the literature are specific enough to arouse suspicion of
      drug-induced pemphigus. Biopsy specimens of drug-induced and idiopathic pemphigus
      were reviewed by five dermatologists with no clinical data available about the
      patients. The sections were assessed to the presence of spongiosis with
      eosinophils, vacuolar degeneration, and the degree of acantholysis and cleavage
      level. Using the suggested criteria, the reviewers were unable to confirm a
      diagnosis of drug-induced pemphigus. It is advisable to consider drug etiology in
      every case of newly diagnosed pemphigus based on clinical criteria an detailed
      drug consumption history, as histologic features do not differentiate between
      drug-associated and idiopathic disease.

PMID- 9261481
TI  - Androgen receptor status of the oral sebaceous glands.
AB  - In recent years, the receptor status of the estrogens and progestins and their
      relationship to the oral mucosa and its disease processes have been described.
      However, investigations regarding the androgens have largely been neglected. The
      androgens have diverse physiologic effects throughput the body and mediate their
      actions through androgen receptors (ARS) in various target organs. One of these,
      the sebaceous gland of the skin (dermal sebaceous gland, DSG) has been evaluated
      extensively in regard to ARS status. However, to our knowledge, the ARS status of
      the oral sebaceous glands (OSG) has not yet been elucidated. We attempt to
      evaluate the ARS status of 10 cases of OSG, in addition to other tissue
      components of the oral mucosa, using immunohistochemical techniques with a
      monoclonal antibody (MoAb) ARS. Sebaceous glands in all cases examined exhibited
      a moderate to more intense degree in immunoreactivity for ARS. Other tissue
      components, however, including the overlying epithelium and vascular endothelium,
      were essentially nonreactive. Our results indicate that, like the DSG, the OSG
      may be a target for the androgenetic hormones.

PMID- 9261482
TI  - Pleomorphic angioleiomyoma.

PMID- 9261483
TI  - Spitz nevus.

PMID- 9261484
TI  - Physician unawareness of serious substance abuse.
AB  - PURPOSE: To describe and assess the prevalence of perceived physician unawareness
      of serious substance abuse. PATIENTS AND METHODS: We report an observational
      study with validation of multivariable results of data collected by interview
      from persons presenting for addictions treatment in the public system who
      reported having a physician. RESULTS: Of 3,253 patients interviewed, 87% (2,843)
      responded to the question about having a physician. Of 1,440 patients who stated
      that they had physicians, 45% (651) reported that the physician who cared for
      them was unaware of their substance abuse. In multivariable logistic regressions
      adjusting for sociodemographics, health status, and substance abuse histories,
      the following patient characteristics were found to be independently associated
      with physician unawareness of substance abuse and were confirmed in a validation
      analysis (OR = Odds Ratio, CI = 95% Confidence Interval); no prior episodic
      medical illness (OR = 1.98, CI = 1.35-2.92), no health insurance (OR = 1.89, CI =
      1.33-2.70), no prior mental health treatment (OR = 1.75, CI = 1.06-2.88), no
      chronic medical illness (OR = 1.69, CI = 1.18-2.40), no prior substance abuse
      treatment (OR 1.64, CI 1.17-2.31), and no prior detoxification (OR = 1.54, CI =
      1.14-2.22). CONCLUSIONS: Forty-five percent of patients with substance abuse
      serious enough to prompt a presentation for treatment stated that the physician
      who cared for them was unaware of their substance abuse. Patients without health
      insurance, a history of medical illness, or prior substance abuse or mental
      health treatment were more likely to have reported physician unawareness. Even
      among substance abusing patients requesting addiction treatment, many perceive
      that their physicians do not recognize their substance abuse.

PMID- 9261485
TI  - Network Therapy for addiction: assessment of the clinical outcome of training.
AB  - Mental health practitioners in the office setting are often seen as deficient in
      addiction treatment skills. Relevant training in often quite limited, and
      trainees are generally not introduced in an effective office-based modality. We
      studied the feasibility of teaching beginning therapists how to apply Network
      Therapy, a cognitive-behavioral approach to achieving abstinence and preventing
      relapse that augments individual therapy with support from family and friends.
      The therapists were 19 psychiatric residents without experience in substance
      abuse treatment or outpatient therapy, and the patients were 24 cocaine-dependent
      patients who received a 24-week course of Network treatment. The patients
      remained in treatment for an average of 15.4 weeks. Seventy-nine percent of their
      observed weekly urine toxicologies were negative for cocaine, and 42% of patients
      produced clean urines in the 3 weeks immediately before termination. The overall
      outcome compares favorably with that reported in studies on cocaine treatment
      where experienced therapists were employed. Our results suggest that naive mental
      health trainees can be taught to apply Network Therapy for effective substance
      abuse management. This is particularly relevant to technology transfer for
      general mental health trainees, who are often thought to be perceived to be
      refractory to learning about the outpatient management of addiction.

PMID- 9261487
TI  - Relationship between self-efficacy perceptions and in-treatment drug use among
      regular cocaine users.
AB  - The perceived ability to engage in situation-specific behaviors (self-efficacy)
      to overcome nicotine dependence and alcohol abuse has been shown to correlate
      significantly with and be predictive of the actual ability to engage in such
      behaviors. Self-efficacy is also related to subsequent behavior change during
      treatment and maintenance of this change after treatment termination. In this
      study, part of national outcome study, the relationship between self-efficacy and
      drug use was investigated in a subsample of regular cocaine users (n = 294) who
      completed at least three months of treatment in community-based outpatient
      treatment programs. Frequency of cocaine and other drug use was reported for the
      period of 1 year before treatment and a 1 month and 3 months in treatment. Self
      efficacy regarding resisting drug use was measured at 1 and 3 months in
      treatment. Self-efficacy at 1 month was correlated with cocaine use at 1 month
      and self-efficacy contributed to the prediction of self-reported drug use at 1
      month over and above pretreatment and demographic variables. Similarly, self
      efficacy at 3 months was correlated with cocaine use at 3 months and contributed
      to the prediction of self-reported drug use at 3 months. These outcomes were
      obtained even though over 75% of subjects reported no drug use during treatment.
      The results supported previous findings suggesting that increased self-efficacy
      regarding resisting drug use is associated with lower rates of drug use during
      treatment, and that self-efficacy enhancement may be an important intervention in
      the treatment of cocaine use.

PMID- 9261486
TI  - Does increasing the opportunity for counseling increase the effectiveness of
      outpatient drug treatment?
AB  - Increasing the opportunity for group and individual counseling in outpatient drug
      treatment programs could increase client participation in counseling which, in
      turn, may enhance program effectiveness. Findings from the evaluation of the Los
      Angeles Target Cities Enhancement Project indicate that the Target Cities
      programs successfully increased client participation in group and individual
      counseling-an increase that cannot be attributed to client characteristics.
      Further, the magnitude of the increase in group and individual counseling was
      sufficient to increase the overall effectiveness of Target Cities programs. These
      findings support the widely held contention among drug treatment providers and
      policy makers that frequent counseling in necessary for treatment success. They
      suggest that counselors and other service providers should encourage and
      facilitate frequent participation in group and individual counseling. Most
      importantly, the findings indicate that increasing the opportunity for group and
      individual counseling will increase client participation in counseling, and this
      increased participation will elevate the overall effectiveness of outpatient drug
      treatment.

PMID- 9261488
TI  - HIV infection risks, behaviors and methadone treatment: client-reported HIV
      infection in a follow-up study of injecting drug users in New England.
AB  - There is wide variation in reported risk factors for HIV incidence among
      injecting drug users by community. Available HIV seroprevalence and incidence
      data indicate that nearly 60% of HIV infection is associated with injecting drug
      use in Connecticut and 48% in Massachusetts. Using 12-month follow-up data on 354
      initially HIV-negative New England (Massachusetts and Connecticut) methadone
      treatment clients, we assessed the association between baseline drug use
      practices, sexual behavior, partner behaviors, and client-reported HIV infection
      during follow-up. Variables that predicted client-reported positive HIV antibody
      test results were modeled by Cox proportional hazards regression. HIV infection
      among those tested was 14.2 per 100 person years (PY) [95% Confidence interval
      (CI) = 9.5 to 21.3]. For each injection the relative risk (RR) was 1.1 (95% CI =
      1.1 to 1.2), for males 3.0 (95% CI = 1.2 to 7.3), for blacks 5.0 (95% CI = 1.6 to
      15.5), for Hispanics 3.6 (95% CI = 1.2 to 10.5). Men who used more than one
      unclean needle per day and had an HIV-infected steady partner had an RR of 28.4
      (95% CI = 4.4 to 176.4). For women, using speedball (RR = 6.1, 95% CI = 1.2 to
      38.8) and being black (RR = 4.4, 95% CI = 1.0 to 19.8) predicted self-reported
      HIV infection; having a steady partner who ever injected increased this risk
      substantially (RR = 65.3, 95% CI = 4.0 to 1046.5). These findings for IDUs in
      Massachusetts and Connecticut indicate that risk factors for HIV infection for
      men are consistent with expected transmission by unclean needles with an HIV
      infected partner, but a preference for using speedball predicted HIV infection
      among women IDUs.

PMID- 9261489
TI  - Drug use history and criminal behavior among 133 incarcerated men.
AB  - The present study investigated the relationship between crime and substance abuse
      in a sample of 133 consecutively evaluated male prisoners. Using the Structured
      Clinical Interview for DSM-III-R, we assessed the prevalence of various forms of
      substance abuse in this population and attempted to judge whether substance abuse
      played a role in the index crime which has led to the present incarceration. In
      addition, we assessed whether there was a relationship between the nature of
      substance dependence and the type of crime committed, whether sexual, violent, or
      non-violent. Among the 133 prisoners, 95% obtained a diagnosis of dependence on
      one or more substances. Fifty-eight percent of the inmates reported that they
      were acutely intoxicated with one or more substances at the time they committed
      the index crime and an additional 6% were withdrawing from a substance at the
      time of the crime. There was no significant correlation between the type of
      substance abuse diagnosis and the type of crime committed. Similarly, there was
      no significant correlation between the number of individuals who reported they
      were intoxicated at the time of the offense and the type of crime committed.

PMID- 9261490
TI  - Do increased levels of drug abuse treatment lead to fewer drug-related problems?
AB  - It has been argued that increased levels of treatment for drug abuse are
      effective in reducing the levels of drug problems. During the 1980s in Ontario
      levels of treatment increased considerably. More treatment facilities were
      opened, and the number of drug abuse cases increased by a factor of about seven.
      It was expected that drug-related problems (mortality, morbidity, and
      convictions) would decrease, as happened for alcohol problems when alcohol
      treatment levels increased. However, the results were inconsistent. Hospital
      separations for drug problems decreased in the late 1970s and then increased in
      the 1980s. However, deaths from drug psychoses and drug dependency showed an
      opposite trend. Convictions for cocaine offences increased while those for
      narcotics, LSD, and hallucinogenic drugs showed a substantial decline from the
      early 1980s to the present. Significant negative correlations (suggestive of a
      beneficial impact) were found between treatment rates and three drug-problem
      measures (deaths rates from drug psychoses and drug dependence, other drug
      related deaths, and convictions under the Food and Drug Act); however, a
      significant positive correlation was found between treatment rates and Narcotic
      Control Act convictions. Thus, although some of the predicted negative
      relationships between treatment rates and drug problems were observed, the
      correlations did not provide a consistent picture of the effects of increased
      drug treatment. More research is needed to identify better indicators of drug
      problems and monitor the factors that influence them.

PMID- 9261491
TI  - Effects of age on perinatal substance abuse among whites and African Americans.
AB  - This descriptive study assessed age effects on perinatal use of alcohol,
      marijuana, and cocaine among African-American and white women. Data were derived
      from the California Perinatal Exposure Study, relying on a statistical
      probability sample n = 29,494) of women who underwent anonymous urine toxicology
      screening in birthing hospitals. The central hypothesis was that there would be
      no difference in age effects on drug use among white and African-American women.
      Marital status and payment source were used as risk factors in order to create
      detailed age-risk profiles for both racial-ethnic groups. Logistic regression
      analyses were used and findings indicated that cocaine use peaked in early
      adulthood for whites and in mid-adulthood for African-Americans who had higher
      prevalence levels with the same or fewer risk factors as whites. Over one third
      of African-American women in their mid-thirties who were not married and who had
      publicly assisted births tested positive for cocaine. In contrast, high risk
      whites had higher marijuana prevalence levels than African-American women, and
      prevalence increased with age. Alcohol prevalence increased with age for African
      American and white women who were publicly assisted, but decreased with age for
      all others. Findings for alcohol and marijuana generally followed the same risk
      adjusted patterns for African American and white women but with different
      prevalence levels; however, cocaine use had a unique pattern with higher
      prevalence among African-American women in mid-adulthood regardless of risk
      level.

PMID- 9261492
TI  - A grounded theory of protecting recovery during transition to motherhood.
AB  - The purpose of this study was to explore women's concurrent experiences of
      alcohol/drug recovery and transition to parenthood. The study used a qualitative
      design to explore and understand women's experiences of recovery from
      alcohol/drug dependence during pregnancy and early parenting. Observation, diary
      entries, and intensive interviews were used for data collection from a purposive
      sample. Eleven women, who self-identified as recovering alcoholics/addicts and
      were either pregnant or had an infant younger than 12 months, participated in the
      study. Findings from descriptive analyses were compared with concepts in the
      literature about the processes of alcohol/drug recovery, relapse prevention and
      transition to motherhood. Balancing emerged as the core concept, a process that
      explained how women successfully integrated the recovery and motherhood processes
      into their identity. The women used strategies learned in the process of
      alcohol/drug recovery to balance between alcohol/drug recovery and motherhood. A
      part of balancing was the use of the protecting strategy in unique ways during
      pregnancy and early parenting to safeguard both recovery and motherhood.
      Understanding concepts and processes associated with the concurrent experiencing
      of recovery and parenthood will be useful to all disciplines that seek to improve
      the health of mothers, infants, and families. This study demonstrates the
      complexity of the women's experiences and suggests implications for practice,
      theory, research, and policy.

PMID- 9261493
TI  - Illegal drug use among rural adults: mental health consequences and treatment
      utilization.
AB  - This study uses the National Household Survey on Drug Abuse to examine mental
      health consequences and treatment utilization among nonmetropolitan and rural
      adults. The study employs an ecological system perspective, dividing the study
      population into three groups: nonmetropolitan-rural, nonmetropolitan-urban, and
      metropolitan-rural. Logistic regression analysis is used to examine four sets of
      factors related to self-report of mental health problems among drug-using adults,
      including community level features, family characteristics, personal
      characteristics, and stress factors. Perceived ease of purchasing cocaine, number
      of moves in last five years, employment in blue-collar occupations, number of
      jobs in last five years, and residence in neighborhoods with a low rate (< 10%)
      of minority households were significantly related to self-report problems.
      Results of the analysis are discussed in terms of barriers to utilization of
      treatment and rehabilitation services among nonmetropolitan and rural adults,
      such as availability and access to facilities and professional services, social
      stigma, ability to afford services, and the difficulty for rural communities to
      support inhospital and outpatient services.

PMID- 9261494
TI  - The China Productivity Project: results and conclusions.
AB  - Experiments were conducted to determine what factors cause variation in
      individual work output (economic productivity). Forty-five young male Chinese
      cycle haulers from Beijing were assessed for physiological work capacity, size
      and body composition, health, nutritional status, cold resistance, household
      social environment, and motivation. Experiments were conducted in the laboratory
      as well as under actual working conditions; ethnographic observations were made
      in the household and on the job during the Beijing winter of 1992. Overall work
      motivation correlated to actual monthly distance/load measures of productivity
      the most strongly (r = 0.518), followed by physiological capacity estimated by
      heart rate:speed ratio during field experiments (r = -0.473). Alcohol consumption
      (a negative factor), household health, and carbohydrate intake were all moderate
      predictors. Maximum oxygen uptake showed lower correlation (r = 0.261), and among
      anthropometric values only relatively long lower legs were predictive (r =
      0.298). Since many of these variable categories were relatively independent of
      each other, multiple regression analysis showed that together they explained
      61.6% of the work output variance. Simultaneous prediction by FASEM (LISREL) is
      also very strong.

PMID- 9261496
TI  - Non-invasive computed tomography and three-dimensional reconstruction of the
      dentition of a 2,800-year-old Egyptian mummy exhibiting extensive dental disease.
AB  - A second CT scan of the mummy Djedmaatesankh, which is housed in the Royal
      Ontario Museum, Toronto, Ontario, has been undertaken after an interval of some
      15 years. The image data set of her dentition and the associated tissues acquired
      from 3 mm thick x 3 mm spacing slices was transferred to an ISG Allegro work
      station where two-dimensional reformats and three-dimensional reconstructions
      were produced. This non-invasive examination provided information on dental
      disease that is, in a number of respects, an advance on that which previously
      could be obtained from mummies by the traditional methods of visual inspection
      after unwrapping and by two-dimensional radiography. The two- and three
      dimensional images reveal that: three molars are missing and the right maxillary
      canine is impacted; the rest of the dentition is afflicted by severe attrition,
      caries and periodontal disease; and, of the 28 teeth present in the mouth, 24
      exhibit exposure of their dental pulps and 18 are afflicted by periapical lesions
      including five that could have contributed to a large secondarily infected
      radicular cyst. The cyst have displaced the maxillary antrum and enlarged the
      maxilla on its lateral aspect and the vault of the palate on its medial aspect.
      Pus from the cyst may have drained through five different sinuses. In life,
      Djedmaatesankh's widespread dental infection probably caused her considerable
      pain, personal distress and malaise, and possibly resulted in her death.

PMID- 9261495
TI  - Maternal proximity and infant CO2 environment during bedsharing and possible
      implications for SIDS research.
AB  - Sudden infant death syndrome (SIDS) is the leading cause of human infant
      mortality after the neonatal period in Western countries. Recently, child care
      practices have been shown to be important in determining infant vulnerability to
      SIDS. However, very little is known about the impact of parent-infant cosleeping
      on infant sleep physiology and behavior and SIDS risk. This reflects the failure
      of Western societal research paradigms to appreciate the human infant's
      evolutionary history of cosleeping, the recency of the emergence of solitary
      infant sleeping as a practice and the fact that parent-infant cosleeping is still
      the preferred sleeping arrangement for the majority of contemporary societies.
      Incorporating current hypotheses on the mechanisms of SIDS, we have hypothesized
      that the comparatively sensory-rich cosleeping environment might be protective
      against SIDS in some contexts. As a first step to characterize cosleeping
      environments, this investigation is aimed at assessing, in routinely bedsharing
      mothers and infants, their relative sleeping positions and the potential for
      sleeping in close face-to face proximity and for infant exposure to increased
      environmental CO2 produced by maternal respiration. The latter is important in
      that breathing elevated levels of CO2 can have diverse effects, ranging from
      respiratory stimulation at low levels to suffocation at very high levels. Two
      related laboratory studies were performed. In the first, all-night videotapes of
      12 healthy, routinely bedsharing mother-infant pairs were analyzed for sleeping
      positions and time spent in face-to-face orientation and distances separating
      their faces. Infants were 11-15 wk old. Mothers predominantly positioned
      themselves on their sides facing their infants, with the infants placed either
      supine or on their sides. Mothers and infants slept oriented face-to-face for 64
      +/- 27% (S.D.) of non-movement time, with distance less than 20 cm commonly
      separating their faces. In the second study, concentrations of CO2 in air were
      measured in six young women at distances of up to 21 cm from their nares. Peak
      expiratory CO2 concentrations remained above 1.0% at distances up to 9 cm and
      above 0.5% at 18 cm. Both baseline and peak CO2 levels were further increased at
      all distances when measured within a partial air pocket created to simulate a
      bedding environment sometimes seen during bedsharing. We conclude that during
      bedsharing there is potential for 1) a high degree of face-to-face orientation
      and close proximity and consequently 2) increased environmental CO2, as a result
      of maternal respiration, to non-lethal levels that might stimulate infant
      respiration. The close proximity would also maximize the sensory impact of the
      mother on the infant through other modalities. We also suggest that bedsharing
      may minimize prone infant positioning, a known risk factor for SIDS.

PMID- 9261497
TI  - Preoperative anthropometric dysmorphology in metopic synostosis.
AB  - Anthropometric identification of dysmorphology in craniofacial anomalies,
      including the craniosynostoses, provides invaluable assistance in clinical
      diagnosis as well as offering a technique for interpreting possible deformities
      in skeletal remains. Premature closure of the metopic suture is a rare form of
      craniosynostosis, representing about 4% of clinically diagnosed synostoses.
      Accompanying this closure are defects of the head and face, particularly the
      upper face and orbits. To identify quantitatively the craniofacial dysmorphology
      associated with metopic synostosis, 50 patients with a diagnosis of primary
      (nonsyndromal) metopic synostosis were examined using a battery of 24
      anthropometric measurements from which 11 proportion indices were calculated. The
      data were compared to sex- and age-matched normal students and converted to
      standard (Z) scores before being analyzed using Student's t-test. The data
      indicate a complex pattern of dysmorphology arising from the synostosis which
      affects the upper face and orbits as well as the cranial vault. The entire fronto
      orbito-zygomatic complex is narrowed, and vertex is reduced. There is
      compensatory sagittal and transverse growth of the posterior neurocranium and
      compensatory vertical and sagittal growth of the upper face. There are
      statistically significant differences in the pattern of dysmorphology between
      patients presenting prior to 6 months of age and those older but not significant
      differences between sexes.

PMID- 9261498
TI  - The coronal pulp cavity index: a biomarker for age determination in human adults.
AB  - The correlation between reduction of the coronal pulp cavity and chronological
      age was examined in a sample of 846 intact teeth from 433 individuals of known
      age and sex. Panoramic (rotational) radiography was used to measure the height
      (mm) of the crown (CH = coronal height) and the height (mm) of the coronal pulp
      cavity (CPCH = coronal pulp cavity height) of 425 premolars and 421 molars from
      213 males and 220 females. The tooth-coronal index (TCI) after Ikeda et al.
      [1985] Jpn. J. For. Med. 39:244-250) was computed for each tooth and regressed on
      real age. The correlation coefficients ranged from -0.92 (molars, combined
      sample, right side) to -0.87 (female molars), with an S.E. of the estimate
      ranging from 5.88-6.66 years. Correlations were slightly higher in males than
      females. The equations obtained allowed estimation of age in a sample of 100
      teeth from both sexes (not used for the regression) with an error of +/- 5 years
      in 81.4% of cases for male molars. The regression formulae for estimating age
      obtained from the recent sample were tested on a historical sample of 100 teeth
      from 100-year-old skeletons with an error of +/- 5 years in 70.3% of cases for
      male molars. This study illustrates the potential value of a little-known aging
      method which can be easily applied to estimate age in both living individuals and
      skeletal material of unknown age.

PMID- 9261499
TI  - The elusive petroexoccipital articulation.
AB  - In the present study, 1,869 skulls from the Hamann-Todd Collection were examined
      (macroscopically and by radiographs) for closure of the petroexoccipital
      articulation (jugular synchrondrosis). The results demonstrated the the
      petroexoccipital articulation underwent closure between 20 and 50 years of age in
      most human skulls evaluated. Approximately 7-10% of the human skulls underwent
      complete union of the petroexoccipital articulation before 20 years of age. In 5
      9% of the population, the joint remained completely open. After 50 years of age,
      there was no increase in the frequency of individuals with incomplete closure.
      The frequency of "partial closure" was similar (4-8%) for all age groups (20-25,
      30-35, 40-45, 50-55, 60-65, and 70+), excluding the 30-35 year old group (17.5%).
      The time interval necessary for closure to occur appeared to be very short. No
      significant differences in closure rates due to ethnic origin, gender, or
      laterality were noted. The utility of the pteroexoccipital articulation as an age
      estimator is discussed.

PMID- 9261500
TI  - Palatal thickening and facial form in Paranthropus: examination of alternative
      developmental models.
AB  - Paranthropus is distinctive among hominoids in its possession of a greatly
      thickened hard palate. Although traditionally considered a structural adaptation
      to counter high-magnitude masticatory stress, alternative developmental models
      are equally viable. Three models of palatal thickening were evaluated in this
      study. A mechanical model interprets palatal thickening as a compensatory
      response to increased instability of the midpalatal suture effected by an
      anterior placement of the masseteric muscle mass. This model predicts that
      palatal thickness is correlated with the length of the palate posterior to the
      masseteric tubercle. Two non-mechanical models consider the thickness of the hard
      palate to be structurally related to and therefore correlated with either 1) the
      degree to which the premaxilla overlaps the hard palate in the subnasal region or
      2) the height of the posterior facial skeleton. The correlation of craniofacial
      variables was assessed intraspecifically in ontogenetic series of great ape and
      human crania. Tests of correlation were performed for each comparison using both
      residuals calculated from reduced major axis regression of the variable of
      interest against a measure of cranial size and shape ratios. A significant
      correlation of palatal thickness with posterior facial height in Pan suggests
      that the unusually thick hard palate of Paranthropus is directly related to the
      increased posterior facial height characteristic of this taxon. Further
      evaluation suggests that extreme palatal thickening in these specimens occurred
      by virtue of their possession of a nasal septum morphology in which the vomer
      extends onto the superior and nasal surface of the premaxilla. Such a morphology
      would have constrained the palatal nasal lamina to maintain the approximate level
      of the premaxillary nasal lamina throughout the growth process thereby promoting
      palatal thickening.

PMID- 9261501
TI  - Why do we fail in aging the skull from the sagittal suture?
AB  - The controversy over the reliability of ectocranial suture status (open vs.
      closed) as an age estimation stimulated the pursuit of Meindl and Lovejoy's
      suggestion (Meindl and Lovejoy [1985] Am. J. Phys. Anthropol. 68:57-66) for large
      scale analysis. The extent of the sagittal suture closure was assessed in 3,636
      skulls from the Hamann-Todd and Terry collections. The debate over whether
      cranial suture ossification represents a pathologic or an age-predictable
      pathologic process also stimulated a comparison with age and two stress markers,
      hyperostosis frontalis interna and tuberculosis. Sagittal suture closure was
      found to be age-independent and sexually biased. The wide confidence intervals
      (for age) appear to preclude meaningful application of suture status for age
      determination. No correlation was found with the tested biological stressors.

PMID- 9261502
TI  - Dental disease in the Chinese Yin-Shang period with respect to relationships
      between citizens and slaves.
AB  - Seventy-one skulls from the Yin-Shang period tombs of Anyang, China, were
      examined for the incidence of observable dental diseases, including dental
      caries, alveolar bone resorption (an index of periodontal disease), ante-mortem
      tooth loss and tooth attrition. Because the remains were excavated from tombs
      with funerary items, the burials are believed to be of Anyang citizens. Our study
      indicates carious tooth frequency in the Yin-Shang period was rather low (2.9
      4.0%). Periodontal disease frequency was 18.3-26.9%, and ante-mortem tooth loss
      frequency was 2.0-7.5%. To determine the relative prevalence of overall dental
      health in the Yin-Shang populations, observations from the 42 male crania were
      compared to those from 183 male crania of slaves from "sacrificial pits" from the
      Yin-Shang period (Inoue et al. [1992] J. Anthropol. Soc. Nippon 100:1-29).
      Results from this comparison indicate no apparent difference between social
      classes in younger age groups. However, in the older ages the rates of the ante
      mortem tooth loss, periodontal disease and tooth attrition were significantly
      higher in the citizen sample. The findings would suggest dietary development in
      the Yin-Shang period was not dissimilar enough between social classes to induce
      clear differences in dental diseases at least at younger ages. Conversely, it
      appears there must have been significant differences between social classes diets
      in the earlier phase of the Yin-Shang period to produce the differences in dental
      disease present in the older samples.

PMID- 9261503
TI  - Brief communication: prehistoric dentistry in the American southwest: a drilled
      canine from Sky Aerie, Colorado.
AB  - A prehistoric Native American mandible from a Fremont site (circa AD 1025) in
      Colorado has a conical pit in the worn occlusal surface of the lower right
      canine. Natural causes for this modification are ruled out by the presence of
      internal striae, a finding confirmed by experimental replication. The canine was
      artificially drilled before the individual's death and is associated with a
      periapical abscess. This is one of a very few examples of prehistoric dentistry
      in the world, and the first from the American Southwest.

PMID- 9261504
TI  - Brief communication: a sample of pediatric skulls available for study.

PMID- 9261506
TI  - Mitochondrial DNA in ancient Amerindians.

PMID- 9261505
TI  - A reevaluation of the cold water etiology of external auditory exostoses.

PMID- 9261507
TI  - Social and reproductive conditions modulate urinary cortisol excretion in black
      tufted-ear marmosets (Callithrix kuhli).
AB  - The links between psychosocial stress, social status, reproductive function, and
      urinary cortisol were assessed in social groups of black tufted-ear marmosets
      (Callithrix kuhli). Urinary cortisol excretion was monitored in cases of
      intrafamily conflict ("sibling fights") and in daughters in four distinct social
      contexts: in the family group, while housed singly or in same-sex pairs, and
      while paired with a male pairmate. Cortisol excretion was elevated in
      participants in intra-family conflict on the day of and the day following the
      conflict, relative to concentrations a week prior to or following the conflict.
      Daughters in natal family groups had concentrations of cortisol that did not
      differ from reproductively active adult females. This finding held for daughters
      who were either anovulatory or undergoing ovulatory cycles while in the natal
      family group. Natal family members and male pairmates exerted buffering effects
      on levels of activity in the hypothalamic pituitary adrenal axis (HPA) in female
      C. kuhli. Placing females in solitary housing led to significantly increased
      cortisol excretion. In the 2 months subsequent to pairing with a male partner,
      excreted cortisol concentrations in females declined significantly. Daughters
      removed from their natal family group and housed with a sister did not exhibit
      increased cortisol levels. These data reveal that activity in the (HPA) axis in
      marmosets is sensitive to psychosocial stressors, and that urinary cortisol can
      provide a useful quantitative measure of HPA reactivity. As in other
      callitrichids, delayed breeding in daughters and reproductive anomalies in C.
      kuhli appear to be mediated by mechanisms other than elevated HPA activity.

PMID- 9261508
TI  - Interactions between infant growth and survival: evidence for selection on age
      specific body weight in captive common marmosets (Callithrix jacchus).
AB  - The objective of this study is to investigate factors influencing infant survival
      in captive common marmosets. We investigated the influence of age-specific
      weight, litter size, caging, and the presence of helpers on survival to 6 months
      of age in 189 Callithrix jacchus infants. Infant survival was analyzed using Cox
      Proportional Hazards regression, and fitness functions were plotted to explore
      the relationship between survival and growth. Results indicate that weights at
      birth and 120 days significantly affect future survival probability. Litter size
      significantly influences survival prior to 60 days of age with larger litters
      having poorer survival. Males and females did not have significantly different
      survival and the presence of helpers in the group did not influence survival
      probability. Patterns of survival with respect to age-specific weights suggest
      stabilizing selection on birth weight and directional selection on weight at 120
      days of age.

PMID- 9261509
TI  - Genetics of adult body mass and maintenance of adult body mass in captive baboons
      (Papio hamadryas subspecies).
AB  - Adult body mass and changes in mass during an individual's life are important
      indicators of general health and reproductive fitness. Therefore,
      characterization of the factors that influence normal variation in body mass has
      important implications for colony management and husbandry. The main objective of
      this study was to quantify the genetic contribution to adult body mass and its
      maintenance in baboons. Intra-individual mean and variance in body mass were
      calculated from multiple weight measures available for each of 1,614 animals at
      least 10 years of age. Heritabilities were estimated using maximum likelihood
      methods. Mean adult body mass had a significant heritability (50%) as did
      variance in adult body mass (12%). The sexes differed in several respects: on
      average females were smaller than males and had greater variability in adult body
      mass; mean and variance in body mass increased with age in females only; and
      number of offspring showed a significant positive relationship with body mass in
      females only. There were significant differences between subspecies in body mass
      as well as ability to maintain body mass. These results indicate that there is a
      significant genetic influence on body mass and its maintenance, and suggest that
      different factors influence changes in body mass with age as well as body mass
      maintenance in male and female baboons.

PMID- 9261510
TI  - Mapping homology between human and black and white colobine monkey chromosomes by
      fluorescent in situ hybridization.
AB  - We used in situ hybridization of chromosome specific DNA probes ("chromosome
      painting") of all human chromosomes to establish homologies between the human and
      the white and black colobus (Colobus guereza 2n = 44). The 24 human paints gave
      31 signals on the autosomes (haploid male chromosomes homologus to human 14 and
      15, 21 and 22, form colobine chromosomes 6 and 16, respectively. Reciprocal
      translocations were found between human chromosomes 1 and 10, 1 and 17, as well
      as 3 and 19. The alternating hybridization signals between human 3 and 19 on
      Colobus chromosome 12 show that in this case a reciprocal translocation was
      followed by a pericentric inversion. The hybridization data show that in spite of
      the same diploid number and similar Fundamental Numbers, the black and white
      colobine monkey differs from Presbytis cristata, an Asian colobine, by 6
      reciprocal translocations. Comparisons with the hybridization patterns in other
      primates show that some Asian colobines have a more derived karyotype with
      respect to African colobines, macaques, great apes, and humans. Chromosome
      painting also clearly shows that similarities in diploid number and chromosome
      morphology both between colobines and gibbons are due to convergence.

PMID- 9261511
TI  - Behavioral and endocrine characteristics of the reproductive cycle in wild
      muriqui monkeys, Brachyteles arachnoides.
AB  - The analysis of fecal ovarian steroids provides a powerful noninvasive method to
      obtain insights into ovulatory cycles, gestation length, and the timing of sexual
      interactions relative to the periovulatory period in wild primates. Techniques
      developed to collect and assay feces from free-ranging muriqui monkeys
      (Brachyteles arachnoides) for estradiol and progesterone yield the first explicit
      reproductive data on this species, and provide the first opportunity to evaluate
      the timing of observed copulations with muriqui ovarian cycles. Hormonal profiles
      from seven females indicate average cycle lengths of 21.0 +/- 5.4 days (n = 20).
      Females conceived after 3-6 ovulatory cycles. Gestation length averaged 216.4 +/-
      1.5 days for the five females for which conception cycles were sampled. Discrete
      copulation periods spanned an average of 2.1 +/- 1.2 days (n = 29), with
      intervals between these concentrated periods of copulations averaging 15.6 +/-
      6.7 days (n = 20). There were no significant differences among females in cycle
      lengths, copulation period lengths, or copulation interval lengths. Ejaculation
      was visible following 71.8 +/- 26.7% of copulations during the females
      preovulatory periods. All females copulated outside the periovulatory period. The
      proportion of copulation days outside the periovulatory period was slightly
      greater (p = 0.08) for primiparous females (64.8 +/- 28.3%) than for multiparous
      females (28.7 +/- 19.7%).

PMID- 9261512
TI  - Steroid excretion during the ovarian cycle in captive and wild muriquis,
      Brachyteles arachnoides.
AB  - Urine, feces, and copulation frequency were collected from two captive muriqui
      females, Brachyteles arachnoides, at the Centro de Primatologia do Rio de Janeiro
      following the resumption of postpartum ovarian cycles. Fecal steroid profiles
      from seven wild muriqui females at the Estacao Biologica de Caratinga, Minas
      Gerais, Brazil, were compared to the captive females to determine the approximate
      patterns of steroid excretion relative to the urinary LH peak. Hormonal profiles
      from one of the captive female muriquis revealed a discrete urinary LH peak. For
      this female, fecal progesterone increased on the same day as the urinary LH peak,
      while fecal estradiol increased 6 days later and urinary steroids increased 5
      days later. For both captive females, the onset of fecal progesterone increase
      was preceded by the onset of copulations, which occurred during at least a 5-day
      period. The complete fecal hormonal profiles of the one captive female for which
      continuos data were available were similar to those found in wild muriqui
      monkeys, with the onset of an increase in sustained progesterone levels occurring
      several days prior to the onset of sustained estradiol increase. These patterns
      suggest that fecal progesterone may be excreted rapidly in this species. The
      onset of sustained increase in fecal progesterone levels, together with the
      consistent delay in the onset of the sustained increase in estradiol, may provide
      the best indicators of the periovulatory period for muriqui females.

PMID- 9261513
TI  - Number of ovulations in the marmoset monkey (Callithrix jacchus): relation to
      body weight, age and repeatability.
AB  - The relation between number of ovulations and body weight, age or maternal
      identity was examined in 69 ovarian cycles from 29 captive-born common marmoset
      monkeys (Callithrix jacchus). Specifically, we addressed the following questions:
      was there high repeatability of ovulation number? Most of the variation in
      ovulation number was within, rather than between subjects. Repeatability in
      number of ovulations was 0.081 (n = 20 females with 2-6 ovulatory cycles per
      female); was age related to number of ovulations? There was no relation between
      age and number of ovulations, either within or between subjects; and was weight
      related to number of ovulations? Weight was related to number of ovulations. When
      the relation between number of ovulations (1-2 versus 3-4) and weight was
      examined through a logistic regression, there was a significant relation. Also,
      of the 11 subjects which had a variable number of ovulations across cycles, 90.9%
      were heavier when ovulating 3-4 than when ovulating 2. These results are
      discussed as the basis for the proposal that callitrichid primates may have been
      selected for potential variation in reproductive output and that this variation
      may be related to energy availability.

PMID- 9261514
TI  - Parity-related differences in suckling behavior and nipple preference among free
      ranging Japanese macaques.
AB  - Suckling behavior of primiparae in free-ranging Japanese macaques (Macaca
      fuscata) was compared with that of multiparae at Jigokudani Monkey Park, the
      Shiga Heights, Nagano Prefecture, Japan, from April 1984 to 1994. The estimated
      rates of milk secretion in a single preferred nipple among primiparae were lower
      than those among multiparae from birth to 5 months of age. Milk secretion
      capabilities of primiparous mothers, hence, appear to be inferior to those of
      multiparous mothers. In nutritive suckling, although Japanese macaque infants
      preferred one single nipple, nipple preferences in primiparae were weaker than
      those in multiparae. With supplementary two-nipple use during suckling, however,
      the infants of primiparae appear to overcome a suckling flaw of their primiparous
      mothers. After infants were 5 months of age and after a drop (from approximately
      10% to approximately 5%) in the rates of milk secretion, however, milk secretion
      rates in a single preferred nipple among primiparae were similar to those in
      multiparae and the supplementary two-nipple use in primiparous mother-infant
      dyads disappeared.

PMID- 9261515
TI  - The strategy of the Commission for cancer research.

PMID- 9261516
TI  - Reshaping Italian AIDS research.

PMID- 9261517
TI  - What are the goals of the CONSORT initiative and what will it achieve?

PMID- 9261518
TI  - The increased armament in the battle against non-small-cell lung cancer.

PMID- 9261519
TI  - Central nervous system relapse of lymphoid malignancies in adults: the role of
      high-dose chemotherapy.
AB  - Adults with CNS recurrence of lymphoid malignancies generally have a very poor
      prognosis. Although recent reports indicate that a proportion of patients may
      obtain prolonged remission after bone marrow transplantation, the role of high
      dose chemotherapy in the management of this complication remains controversial.
      We reviewed the literature in order to better evaluate the relative contribution
      of high-dose chemotherapy to the outcome of patients with CNS recurrence. We
      focused mainly on results in adults, but included results on pediatric patients
      when relevant. Our review of the data indicates that 20% to 40% of adults with a
      history of CNS involvement by lymphoma or lymphoid leukemia can be cured by high
      dose chemotherapy. A small fraction of patients with active CNS involvement can
      be cured as well. No data is available to determine superiority of a particular
      conditioning regimen or of allogeneic vs. autologous BMT. There is no conclusive
      benefit to post-transplant intrathecal therapy and the role of cranial or cranio
      spinal radiation treatment and its optimal timing remains to be determined.
      Prospective studies are needed to resolve many of the issues regarding the
      treatment, and to improve the outcome of patients with CNS recurrence of lymphoid
      malignancies.

PMID- 9261520
TI  - Single-agent gemcitabine versus cisplatin-etoposide: early results of a
      randomised phase II study in locally advanced or metastatic non-small-cell lung
      cancer.
AB  - BACKGROUND: This randomised study was designed to determine the response rate
      survival and toxicity of single-agent gemcitabine and cisplatin-etoposide in
      chemo-naive patients with locally advanced or metastatic non-small-cell lung
      cancer. PATIENTS AND METHODS: Gemcitabine 1,000 mg/m2 was given as a 30 min
      intravenous infusion on days 1, 8, 15 of a 28-day cycle, cisplatin 100 mg/m2 on
      day 1, and etoposide 100 mg/m2 on days 1 (following cisplatin), 2 and 3. Major
      eligibility criteria included histologically confirmed non-small-cell lung
      cancer, measurable disease, Zubrod PS 0-2; no prior chemotherapy, no prior
      radiation of the measured lesion, and no CNS metastases. RESULTS: 146 patients
      were enrolled, 71 patients on gemcitabine and 75 patients on cisplatin-etoposide.
      Patient characteristics were well matched across both arms. Sixty-six gemcitabine
      patients and 72 cisplatin-etoposide patients were evaluable. Partial responses
      were seen in 12 gemcitabine patients (18.2%; 95% CI: 9.8-30) and 11 cisplatin
      etoposide patients (15.3%; 95% CI: 7.9-25.7). Early indications show no
      statistical differences between the two treatments with respect to time to
      disease progression or survival. Haematological and laboratory toxicity were
      moderate and manageable. However, hospitalisation because of neutropenic fever
      was required for 6 (8%) cisplatin-etoposide patients but not for any gemcitabine
      patients. Non-haematological toxicity was more pronounced with significant
      differences in nausea and vomiting (grade 3 and 4: 11% gemcitabine vs. 29%
      cisplatin-etoposide; despite the allowance for 5-HT3 antiemetics during the first
      cycle of cisplatin-etoposide), and alopecia (grade 3 and 4:3% gemcitabine vs. 62%
      cisplatin-etoposide). CONCLUSIONS: In this randomised study, single-agent
      gemcitabine was at least as active but better tolerated than the combination
      cisplatin-etoposide.

PMID- 9261521
TI  - Postchemotherapy resections of residual masses from metastatic non-seminomatous
      testicular germ cell tumors.
AB  - PURPOSE: To analyse the frequencies of histological findings, predictive factors
      for the presence of undifferentiated tumor and variables influencing the survival
      of patients with non-seminomatous germ cell tumors who underwent secondary
      resection of residual masses after cisplatin-based combination chemotherapy.
      PATIENTS AND METHODS: 134 patients with a median age of 26 years (15-47)
      undergoing at least one surgical intervention at Hannover University Medical
      School were included. One hundred nine patients had received first-line
      chemotherapy and 25 underwent surgery after second-line chemotherapy. RESULTS:
      After first-line chemotherapy the distribution of histological findings was 52%
      necrosis, 27% differentiated teratoma and 21% undifferentiated tumor for 82
      patients with marker negative PR (PRm-). Incompletely resected mass and failure
      to achieved complete tumor marker normalisation were significantly associated
      with the finding of undifferentiated tumor. Five-year progression-free survival
      rates according to histological findings were 78%, 67% and 66% for necrosis,
      differentiated teratoma and undifferentiated tumor. Patients with
      undifferentiated tumor in the resected specimen routinely received postoperative
      additional chemotherapy. Factors associated with a worse overall survival were
      progressive disease within three months, persistent AFP elevation prior to
      surgery, prechemotherapy elevated LDH levels or mediastinal lymph node
      involvement at primary diagnosis. In 8 of 27 patients (30%) undergoing multiple
      resections at different sites a dissimilar histology was found. In the 25
      patients operated after salvage chemotherapy undifferentiated tumor was found in
      80%. A five-year survival of 44% compared to 80% after first-line chemotherapy
      was achieved. CONCLUSIONS: Resection of residual tumors after first-line
      chemotherapy remains essential in the treatment of metastatic testicular cancer.
      Undifferentiated tumor may still be found in 20% of patients despite achieving
      PRm-after first-line chemotherapy. Necrosis is found in only 50% of marker
      normalized patients after first-line and approximately 30% after second-line
      chemotherapy. Future studies have to prove whether the combination of clinical
      prognostic factors and the use of PET-scanning will allow to spare subsets of
      patients from secondary resection.

PMID- 9261522
TI  - Maximum tolerable doses of intravenous zidovudine in combination with 5
      fluorouracil and leucovorin in metastatic colorectal cancer patients. Clinical
      evidence of significant antitumor activity and enhancement of zidovudine-induced
      DNA single strand breaks in peripheral nuclear blood cells.
AB  - BACKGROUND: Experimental studies have demonstrated that 5-fluorouracil (5-FU)
      enhances zidovudine (AZT)-induced DNA strand breaks and cytotoxicity. Phase I
      studies have demonstrated that the maximum tolerable dose (MTD) of AZT is 8000
      mg/sqm when administered i.v. over two hours after weekly 5-FU + l-leucovorin
      (LV), and that this combination has promising antitumor activity. The purpose of
      this study was therefore to evaluate the antitumor activity of weekly bolus 5-FU
      + LV + AZT, administered at its MTD, and to determine whether 5-FU enhances AZT
      induced DNA strand breaks in blood nuclear cells. PATIENTS AND METHODS: Twenty
      nine chemotherapy-naive metastatic colorectal cancer patients with measurable
      disease entered the study to evaluate the activity of a weekly 5-FU 500 mg/m2
      i.v. bolus + LV 250 mg/m2 i.v. two-hour infusion + AZT 8000 mg/m2 i.v. two-hour
      infusion. In 10 different patients, who during three different weeks received 5
      FU + LV, AZT and 5-FU + LV + AZT, DNA strand breaks in blood nuclear cells were
      determined by a fluorescent analysis of DNA unwinding. RESULTS: Treatment was
      generally well tolerated and WHO grades III-IV toxicities, consisting mostly of
      diarrhea (17%), were uncommon. One patient died of severe diarrhea with
      consequent hypokalemia and cardiac arrhythmia. All patients were considered
      evaluable for response, and 3 (10%) complete and 10 (35%) partial responses were
      observed, for an objective response rate of 45% (95% confidence limit interval
      26%-64%). Both 5-FU + LV and AZT decreased the percentage of double stranded DNA
      in nuclear blood cells. The greatest effect was observed with 5-FU + LV + AZT,
      which reduced the percentage of double stranded DNA to 50% and 36% after 24 and
      48 hours, respectively, and this interaction between 5-FU + LV and AZT was found
      to be cumulative. CONCLUSIONS: These studies demonstrate that the present dose
      and schedule of AZT in combination with 5-FU + LV has significant activity in
      metastatic colorectal cancer and that the combination of 5-FU + LV with AZT
      increases the amount of DNA damage. Therefore, AZT in combination with 5-FU + LV
      warrants further study in colorectal cancer.

PMID- 9261523
TI  - Pretreatment prognostic factors for survival in small-cell lung cancer: a new
      prognostic index and validation of three known prognostic indices on 341
      patients.
AB  - AIMS: a) To identify which pretreatment clinical or blood parameters were
      predictive of patients survival in small-cell lung cancer (SCLC) in a
      retrospective analysis. b) To validate three known prognostic indices: Royal
      Marsden Model (index 1), London Group (index 2) and Manchester Score (index 3).
      PATIENTS AND METHODS: From 1981 to 1993, 341 SCLC patients were treated with
      chemotherapy with or without surgery or radiotherapy. Univariate and multiple
      regression analyses of survival were performed and the feasibility of these
      models was explored, index 1: Karnofsky index, albumin, sodium and alkaline
      phosphatase; index 2: ECOG performance status (PS), albumin and alanine
      transaminase; and index 3; lactate dehydrogenase (LDH), disease extent, sodium,
      Karnofsky index, alkaline phosphatase and bicarbonate. RESULTS: Significant
      prognostic factors for survival after univariate and multiple regression analysis
      were: disease extent, PS, creatine kinase, neutrophilia, LDH, hypoalbuminemia,
      hyperglycemia and bicarbonate. A new prognostic index was performed that included
      LDH, hypoalbuminemia, neutrophilia, disease extent and PS. It defined three
      prognostic groups (PG). Median survival and two-year survival for these PG were
      12.3, 8 and 3.4 months and 16.5%, 2.3% and 0%, respectively. The following PG
      were identified after application of the three models proposed: Index 1
      identified two PG with 0% and 16.6% two-year survival (P < 0.001); index 2
      detected three PG with 0%, 5% and 15.7% two-year survival (P < 0.001) and index 3
      detected three PG with 0%, 2.5% and 16.2% two-year survivals, respectively (P <
      0.001). CONCLUSION: A new prognostic index is proposed allowing identification of
      three different PG. The feasibility of three known prognostic models was
      validated and demonstrated. Variables other than disease extent or PS (albumin or
      LDH) should be taken into account in designing future clinical trials.

PMID- 9261524
TI  - Mediastinal non-seminomatous germ cell tumours (MNSGCT) treated with cisplatin
      based combination chemotherapy.
AB  - BACKGROUND: Primary mediastinal non-seminomatous germ cell tumours (MNSGCT)
      constitute a rare malignancy. This study was performed to review our experience
      with cisplatin-based chemotherapy in patients with MNSGCT. PATIENTS AND METHODS:
      Patients with MNSGCT treated with cisplatin-based combination chemotherapy
      between 1978-1995 in three university hospitals in Spain were retrospectively
      studied. RESULTS: There were 25 males and two females with a median age of 26
      years (range 4-71). Fifteen patients had disease confined to the mediastinum and
      12 had metastatic disease. All patients were treated with cisplatin chemotherapy
      regimens (PVB: 7, BEP: 6, and other regimens 12) and considered for residual mass
      surgery (RMS) when indicated. Eleven patients (40.7%) were rendered disease-free
      with initial treatment: four with chemotherapy alone, one with surgery plus
      adjuvant chemotherapy and six with chemotherapy plus RMS. Three of these patients
      relapsed at two, six and seven months. The remaining 16 had unfavourable
      responses (five partial response, three no change, seven progressive disease and
      one toxic death). Eleven patients received salvage treatment but none of them
      achieved a durable response. After a median follow-up of 77 months (range 1-168),
      10 patients remain alive. Actuarial survival at five years is 31.7%. No patients
      in this series developed a haematological malignancy. Chromosomal analysis showed
      that 2 out of 10 patients (20%) had a 47XXY karyotype. CONCLUSIONS: Only patients
      who achieved disease-free status are likely to be cured. Therefore, new up-front
      strategies are needed for the treatment of MNSGCT.

PMID- 9261525
TI  - Delayed emesis induced by moderately emetogenic chemotherapy: do we need to treat
      all patients? The Italian Group for Antiemetic Research.
AB  - BACKGROUND: The pattern and prognostic factors of delayed nausea and vomiting
      induced by moderately emetogenic chemotherapy have not yet been adequately
      studied. PATIENTS AND METHODS: Data are derived from a large and well defined
      population of patients studied to evaluate the efficacy and tolerability of
      granisetron, dexamethasone and their combination in the control of acute emesis
      over repeated cycles of moderately emetogenic chemotherapy. Patients were
      monitored on days 2-5 without receiving any prophylactic treatment for delayed
      emesis. RESULTS: There were 395 evaluable patients at the first, 352 at the
      second and 319 at the third cycle of chemotherapy. Overall, 32.7% patients
      suffered symptoms of delayed vomiting and/or moderate-severe nausea at the first,
      32.1% at the second and 35.1% at the third cycle of chemotherapy. More precisely,
      the incidence of delayed vomiting was 21.3% at the first, 18.5% at the second and
      21.0% at the third cycle of chemotherapy, while the incidence of delayed moderate
      severe nausea was 25.1%, 25.0% and 26.0%, respectively. The incidence of delayed
      vomiting and moderate-severe nausea was very low in patients who obtained good
      control of acute vomiting and moderate-severe nausea, but it remained substantial
      in patients who experienced them during the first 24 hours after chemotherapy. In
      fact, at first/second/third cycle of chemotherapy delayed vomiting occurred in
      12.3%/11.8%/ 13.1% of patients who did not suffer from acute vomiting and in
      54.1%/48.4%/55.9% of those who had acute vomiting, respectively, Similar data
      were obtained for delayed moderate-severe nausea. CONCLUSIONS: Patients without
      acute vomiting or moderate-severe acute nausea may not need any antiemetic
      prophylaxis for delayed vomiting or nausea, while those with a history of acute
      vomiting or moderate-severe acute nausea should always be treated for delayed
      emesis. Selection bias and dependence effect of delayed emesis on acute emesis
      can cause misinterpretation of data derived from clinical trials in patients
      submitted to multiple cycles of chemotherapy.

PMID- 9261526
TI  - Glutathione reduces the toxicity and improves quality of life of women diagnosed
      with ovarian cancer treated with cisplatin: results of a double-blind, randomised
      trial.
AB  - BACKGROUND: Early clinical trials have suggested that glutathione (GSH) offers
      protection from the toxic effects of cisplatin. PATIENTS AND METHODS: One hundred
      fifty-one patients with ovarian cancer (stage I-IV) were evaluated in a clinical
      trial of cisplatin (CDDP) +/- glutathione (GSH). The objective was to determine
      whether GSH would enhance the feasibility of giving six cycles of CDDP at 100
      mg/m2 without dose reduction due to toxicity. RESULTS: When considering the
      proportion of patients receiving six courses of CDDP at any dose, GSH produced a
      significant advantage over control--58% versus 39%, (P = 0.04). For these
      patients there was a significant difference between the reduction in creatinine
      clearance for GSH treated patients compared with control--74% versus 62% (P =
      0.006). Quality of life scores demonstrated that for patients receiving GSH there
      was a statistically significant improvement in depression, emesis, peripheral
      neurotoxicity, hair loss, shortness of breath and difficulty concentrating. As an
      indication of overall activity, these patients were statistically significantly
      more able to undertake housekeeping and shopping. Clinically assessed response to
      treatment demonstrated a trend towards a better outcome in the GSH group (73%
      versus 62%) but this was not statistically significant (P = 0.25). CONCLUSIONS:
      The results demonstrate that adding GSH to CDDP allows more cycles of CDDP
      treatment to be administered because less toxicity is observed and the patient's
      quality of life is improved.

PMID- 9261527
TI  - Preliminary results of a phase II study of high-dose radiation therapy and
      neoadjuvant plus concomitant 5-fluorouracil with CDDP chemotherapy for patients
      with anal canal cancer: a French cooperative study.
AB  - BACKGROUND: Chemotherapy (5-fluorouracil-mitomycin C) concomitant with
      radiotherapy (RT) increases local control and colostomy-free survival in advanced
      anal canal carcinomas (ACC). The purpose of this prospective trial was to analyse
      the toxicity of and response to an induction chemotherapy combining 5
      fluorouracil (5-FU) and CDDP administered concomitantly with irradiation.
      PATIENTS AND METHODS: Thirty patients (24 F/6 M, mean age 60, range 38-74) with
      an advanced ACC > 40 mm and/or with node involvement were prospectively treated
      (1 T1, 16 T2, 8 T3, 5 T4, 10 N1, 1 N2, 8 N3) from November 1994 to January 1996.
      Two induction and two concomitant cycles of 5-FU (800 mg/ m2 D1-4 infusion) and
      CDDP (80 mg/i.v./m2 at D1) were delivered. RT consisted of 45 Gy (1.8 Gy/fr, 5
      fr/w) on pelvis +/- inguinal nodes or 30 Gy (3 Gy/fr, 4 fr/w) by direct perineal
      field. A boost (15-20 Gy) was delivered six weeks later. RESULTS:  TOXICITY: one
      patient died of a pulmonary embolism on D4. The remaining 29 received the entire
      treatment, with reduced 5-FU doses in 11 patients because of acute toxicity. The
      RT boost was delayed for one patient (aplasia). In 109 cycles, 3 grade 4 and 17
      grade 3 toxicities were observed; there were no toxic deaths. Tumor response: the
      complete response (CR) and partial response (PR) rates were, respectively, 11%
      and 61% after induction chemotherapy, 59% and 31% after concomitant
      radiochemotherapy and 96% and 0% two months after completion of the treatment. No
      tumor progression was observed. CONCLUSION: the treatment was well tolerated and
      there was good compliance. After induction chemotherapy, most of the patients
      were in PR, with some even in CR. After completion of the treatment all but one
      were in CR. The tumor response and the long term results of 50 patients will be
      analysed before initiation of a randomised trial is considered.

PMID- 9261528
TI  - Peripheral T-cell lymphomas. Clinico-pathologic study of 168 cases diagnosed
      according to the R.E.A.L. Classification.
AB  - BACKGROUND: One hundred sixty-eight peripheral T-cell lymphomas (PTCLs) were
      reviewed according to the Revised European-American Lymphoma (R.E.A.L.)
      Classification. PATIENTS AND METHODS: The cases, originally diagnosed on the
      basis of the Updated Kiel Classification (UKC), were all provided with
      histological preparations, immunophenotype, clinical information, and follow-up
      data. The slides were reclassified by five observers, who integrated the R.E.A.L.
      criteria with cell size measurements. The prognostic value of clinical and
      pathologic findings was assessed by univariate and multivariate analysis.
      RESULTS: The R.E.A.L. Classification was reproducibly applied by all of the
      observers. Clinically, anaplastic large cell lymphomas (ALCLs) differed from the
      remaining PTCLs by mean age (29.5 vs. 52.9 years), bulky disease (52.3% vs.
      11.3%; P = 0.000), mediastinal mass (52.7% vs. 32%; P = 0.004), and disease-free
      survival (68.0% vs. 38.2%; P = 0.0001). Although each histological type displayed
      specific clinical aspects, PTCLs other than ALCL were basically characterised by
      a poor clinical outcome which was not influenced by the UKC malignancy grade. At
      multivariate analysis, the risk of a lower complete remission rate was related to
      bulky disease (P = 0.001), histologic group (non-ALCL) (P = 0.01), and advanced
      stage (III-IV) (P = 0.0002). CONCLUSIONS: The present study supports the
      classification of T-cell lymphomas proposed by the R.E.A.L. scheme.

PMID- 9261529
TI  - Neurologic complications of Hodgkin's disease: a case history.

PMID- 9261530
TI  - Treatment of angioimmunoblastic T-cell lymphoma with cyclosporine.

PMID- 9261531
TI  - Phase II trial of the oral platinum complex JM216 in non-small-cell lung cancer:
      an EORTC early clinical studies group investigation.
AB  - BACKGROUND: JM216 is a new oral platinum complex with dose-limiting toxicity
      myelosuppression, now undergoing phase II evaluation. PATIENTS AND METHODS: JM216
      was evaluated as first line therapy in non-small-cell lung cancer. Seventeen
      patients received 120 mg/m2/day for five days repeated every three weeks.
      RESULTS: Toxicity was manageable, the commonest side-effects being nausea,
      vomiting, diarrhoea, constipation and asthenia. Myelososuppression was generally
      grade < 2 and there were no cases of neutropenic sepsis or bleeding. Thirteen
      patients were fully evaluable for response. No sustained objective responses were
      reported. One patient was reported as stable disease had a partial response after
      three courses but was progressing again after four. An additional five patients
      had stable disease (46.2%). CONCLUSIONS: Although some patients may have had
      useful palliation, JM216 did not appear to have significant antitumour activity
      in non-small-cell lung cancer.

PMID- 9261532
TI  - How to predict carboplatin clearance from standard morphological and biological
      characteristics in obese patients.
AB  - BACKGROUND: We previously proposed a formula to predict carboplatin clearance
      (CL) from four patient characteristics: plasma creatinine level, body weight,
      age, and sex (J Natl Cancer Inst 1995; 87: 573). Its accuracy was studied in a
      subpopulation of obese patients. PATIENTS AND METHODS: Twenty-five patients (16
      male and 9 female, 23 to 82 years old) were studied. They were 20% to 67% (median
      36%) over the ideal weight which was calculated according to the Lorentz
      equation. Their actual CL was obtained individually by the Siphar program. The
      pharmacokinetic population program NONMEM was used to determine the best value of
      substitution for weight in the formula. RESULTS: By using the actual weight, CL
      was significantly over predicted (by more than 20% for 7 of 25 patients). By
      using the mean value between the ideal and the actual weight, a good prediction
      of CL was obtained: the percentage of error ranged from -21% to +22%. CONCLUSION:
      The formula is applicable to obese patients if both ideal and actual weights are
      taken into account.

PMID- 9261533
TI  - Short-course intravenous prophylaxis for paclitaxel-related hypersensitivity
      reactions.
AB  - PURPOSE: To estimate the incidence of hypersensitivity reactions using a short
      course intravenous prophylactic regimen in patients receiving outpatient therapy
      with paclitaxel. PATIENTS AND METHODS: Patients were identified from a
      retrospective search of a computerized pharmacy database covering a two-year
      period from January 1994 through December 1995. Eligible outpatients received
      paclitaxel as a one- to three-hour infusion 30 minutes after intravenous
      dexamethasone (10 or 20 mg), diphenhydramine (50 mg), and cimetidine (300 mg) or
      ranitidine (50 mg). Charts from all patients were then manually reviewed to
      verify drug administration and to record any evidence of hypersensitivity
      reactions during the first two cycles of therapy. RESULTS: A total of 283
      outpatients were identified from the pharmacy database and all charts reviewed.
      All patients received intravenous dexamethasone (5 to 20 mg) 30 minutes prior to
      paclitaxel without prior oral dexamethasone. Hypersensitivity reactions were
      documented in 13 patients (4.6%) during the first or second cycle with a 95%
      confidence interval (CI) of 2.2% to 7.0%. Reactions resolved rapidly without
      sequelae and did not require hospitalization. Only two reactions (0.7%) were
      graded as serious with a 95% CI of 0.2% to 1.2%, based on the use of
      bronchodilators and presence of angioedema. Therapy was continued with
      modification in 10 patients without recurrent hypersensitivity reaction. Therapy
      was discontinued in two patients without rechallenge and discontinued in one
      patient after rechallenge with a recurrent hypersensitivity reaction. CONCLUSION:
      A short-course single-dose regimen of intravenous dexamethasone, diphenhydramine,
      and cimetidine (or ranitidine) offers a safe and convenient alternative for
      prevention of hypersensitivity reactions associated with outpatient paclitaxel
      administration.

PMID- 9261534
TI  - The control of delayed nausea.

PMID- 9261535
TI  - Sexuality in women receiving chemotherapy for breast cancer.

PMID- 9261536
TI  - Thresholds of microwave-evoked warmth sensations in human skin.
AB  - We measured thresholds for microwave-evoked skin sensations of warmth at
      frequencies of 2.45, 7.5, 10, 35, and 94 GHz. In the same subjects, thresholds of
      warmth evoked by infrared radiation (IR) were also measured for comparison.
      Detection thresholds were measured on the skin in the middle of the back in 15
      adult male human subjects at all microwave (MW) frequencies and with IR. Long
      duration (10-s), large area (327-cm2) stimuli were used to minimize any
      differential effects of temporal or spatial summation. Sensitivity increased
      monotonically with frequency throughout the range of microwave frequencies
      tested. The threshold at 94 GHz (4.5 +/- 0.6 mW/cm2) was more than an order of
      magnitude less than at 2.45 GHz (63.1 +/- 6.7 mW/cm2), and it was comparable to
      the threshold for IR (5.34 +/- 1.07 mW/cm2).

PMID- 9261537
TI  - Increased resorptions in CBA mice exposed to low-frequency magnetic fields: an
      attempt to replicate earlier observations.
AB  - This paper has two aims. First, it reports the findings of a study on the effects
      of low-frequency magnetic fields on reproduction. Second, it serves as an example
      of an attempt to replicate the results of an experimental study in an independent
      laboratory and discusses some of the problems of replication studies. To try to
      replicate the findings of a study reporting increased resorptions (fetal loss) in
      mice exposed to 20 kHz magnetic fields with sawtooth waveform and to study the
      possible effects of 50 Hz sinusoidal fields, pregnant mice were exposed to
      magnetic fields from day 0 to 18 of pregnancy, 24 h per day. The flux densities
      of the vertical magnetic fields were 15 microT (peak-to-peak) at 20 kHz and 13 or
      130 microT (root mean square) at 50 Hz. Two strains of animals were used: CBA/S
      mice imported from the laboratory reporting the original observations, and a
      closely related strain CBA/Ca. The CBA/S mice were cleaned of pathogenic microbes
      and parasites before they were imported into our laboratory. The magnetic field
      exposures did not affect resorption rate in CBA/Ca mice. In CBA/S, the frequency
      of resorptions was higher in the exposed mice than in the control group. However,
      the increase was not significantly different from either the no-effect hypothesis
      or the results of the original study we were attempting to replicate. Differences
      between the two studies and difficulties in interpreting the results are
      discussed. It is concluded that the results tend more to support than argue
      against increased resorptions in CBA/S mice exposed to the 20 kHz magnetic field.
      The results demonstrate that animal strain is an important variable in
      bioelectromagnetics research: even closely related strains may show different
      responses to magnetic field exposure.

PMID- 9261538
TI  - Mortality of plastic-ware workers exposed to radiofrequencies.
AB  - The mortality experience of a cohort of Italian plastic-ware workers exposed to
      radiofrequency (RF)-electromagnetic fields generated by dielectric heat sealers
      was investigated. Follow-up extended from 1962 to 1992. The standardised
      mortality ratio (SMR) analysis was restricted to 481 women workers, representing
      78% of the total person-years at risk. Mortality from malignant neoplasms was
      slightly elevated, and increased risks of leukemia and accidents were detected.
      The all-cancer SMR was higher among women employed in the sealing department,
      where exposure to RF occurred, than in the whole cohort. This study raises
      interest in a possible association between exposure to RF radiation and cancer
      risk. However, the study power was very small, and the possible confounding
      effects of exposure to solvents and vinyl chloride monomer (VCM) could not be
      ruled out. The hypothesis of an increased risk of cancer after radiofrequency
      exposure should be further explored by means of analytical studies characterised
      by adequate power and more accurate exposure assessment.

PMID- 9261539
TI  - Bioeffects induced by exposure to microwaves are mitigated by superposition of
      ELF noise.
AB  - We have previously demonstrated that microwave fields, amplitude modulated (AM)
      by an extremely low-frequency (ELF) sine wave, can induce a nearly twofold
      enhancement in the activity of ornithine decarboxylase (ODC) in L929 cells at SAR
      levels of the order of 2.5 W/kg. Similar, although less pronounced, effects were
      also observed from exposure to a typical digital cellular phone test signal of
      the same power level, burst modulated at 50 Hz. We have also shown that ODC
      enhancement in L929 cells produced by exposure to ELF fields can be inhibited by
      superposition of ELF noise. In the present study, we explore the possibility that
      similar inhibition techniques can be used to suppress the microwave response. We
      concurrently exposed L929 cells to 60 Hz AM microwave fields or a 50 Hz burst
      modulated DAMPS (Digital Advanced Mobile Phone System) digital cellular phone
      field at levels known to produce ODC enhancement, together with band-limited 30
      100 Hz ELF noise with root mean square amplitude of up to 10 microT. All
      exposures were carried out for 8 h, which was previously found to yield the peak
      microwave response. In both cases, the ODC enhancement was found to decrease
      exponentially as a function of the noise root mean square amplitude. With 60 Hz
      AM microwaves, complete inhibition was obtained with noise levels at or above 2
      microT. With the DAMPS digital cellular phone signal, complete inhibition
      occurred with noise levels at or above 5 microT. These results suggest a possible
      practical means to inhibit biological effects from exposure to both ELF and
      microwave fields.

PMID- 9261540
TI  - The effect of pulsed and sinusoidal magnetic fields on the morphology of
      developing chick embryos.
AB  - Several investigators have reported robust, statistically significant results
      that indicate that weak (approximately 1 microT) magnetic fields (MFs) increase
      the rate of morphological abnormalities in chick embryos. However, other
      investigators have reported that weak MFs do not appear to affect embryo
      morphology at all. We present the results of experiments conducted over five
      years in five distinct campaigns spanning several months each. In four of the
      campaigns, exposure was to a pulsed magnetic field (PMF); and in the final
      campaign, exposure was to a 60 Hz sinusoidal magnetic field (MF). A total of over
      2500 White Leghorn chick embryos were examined. When the results of the campaigns
      were analyzed separately, a range of responses was observed. Four campaigns
      (three PMF campaigns and one 60 Hz campaign) exhibited statistically significant
      increases (P > or = 0.01), ranging from 2-fold to 7-fold, in the abnormality rate
      in MF-exposed embryos. In the remaining PMF campaign, there was only a slight
      (roughly 50%), statistically insignificant (P = 0.2) increase in the abnormality
      rate due to MF exposure. When the morphological abnormality rate of all of the
      PMF-exposed embryos was compared to that of all of the corresponding control
      embryos, a statistically significant (P > or = .001) result was obtained,
      indicating that PMF exposure approximately doubled the abnormality rate. Like
      wise, when the abnormality rate of the sinusoid-exposed embryos was compared to
      the corresponding control embryos, the abnormality rate was increased
      (approximately tripled). This robust result indicates that weak EMFs can induce
      morphological abnormalities in developing chick embryos. We have attempted to
      analyze some of the confounding factors that may have contributed to the lack of
      response in one of the campaigns. The genetic composition of the breeding stock
      was altered by the breeder before the start of the nonresponding campaign. We
      hypothesize that the genetic composition of the breeding stock determines the
      susceptibility of any given flock to EMF-induced abnormalities and therefore
      could represent a confounding factor in studies of EMF-induced bioeffects in
      chick embryos.

PMID- 9261541
TI  - Intracellular calcium signaling by Jurkat T-lymphocytes exposed to a 60 Hz
      magnetic field.
AB  - To explore possible biochemical mechanisms whereby electromagnetic fields of
      around 0.1 mT might affect immune cells or developing cancer cells, we studied
      intracellular calcium signaling in the model system Jurkat E6-1 human T-leukemia
      cells during and following exposure to a 60 Hz magnetic field. Cells were labeled
      with the intracellular calcium-sensitive fluorescent dye Fluo-3, stimulated with
      a monoclonal antibody against the cell surface structure CD3 (associated with
      ligand-stimulated T-cell activation), and analyzed on a FACScan flow-cytometer
      for increases in intensity of emissions in the range of 515-545 nm. Cells were
      exposed during or before calcium signal-stimulation to 0.15 mTrms 60 Hz magnetic
      field. The total DC magnetic field of 78.2 microT was aligned 17.5 degrees off
      the vertical axis. Experiments used both cells cultured at optimal conditions at
      37 degrees C and cells grown under suboptimal conditions of 24 degrees C, lowered
      external calcium, or lowered anti-CD3 concentration. These experiments
      demonstrate that intracellular signaling in Jurkat E6-1 was not affected by a 60
      Hz magnetic field when culture and calcium signal-stimulation were optimal or
      suboptimal. These results do not exclude field-induced calcium-related effects
      further down the calcium signaling pathway, such as on calmodulin or other
      calcium-sensitive enzymes.

PMID- 9261542
TI  - Melatonin and a spin-trap compound block radiofrequency electromagnetic radiation
      induced DNA strand breaks in rat brain cells.
AB  - Effects of in vivo microwave exposure on DNA strand breaks, a form of DNA damage,
      were investigated in rat brain cells. In previous research, we have found that
      acute (2 hours) exposure to pulsed (2 microseconds pulses, 500 pps) 2450-MHz
      radiofrequency electromagnetic radiation (RFR) (power density 2 mW/cm2, average
      whole body specific absorption rate 1.2 W/kg) caused an increase in DNA single-
      and double-strand breaks in brain cells of the rat when assayed 4 hours post
      exposure using a microgel electrophoresis assay. In the present study, we found
      that treatment of rats immediately before and after RFR exposure with either
      melatonin (1 mg/kg/injection, SC) or the spin-trap compound N-tert-butyl-alpha
      phenylnitrone (PBN) (100 mg/kg/injection, i.p.) blocks this effects of RFR. Since
      both melatonin and PBN are efficient free radical scavengers it is hypothesized
      that free radicals are involved in RFR-induced DNA damage in the brain cells of
      rats. Since cumulated DNA strand breaks in brain cells can lead to
      neurodegenerative diseases and cancer and an excess of free radicals in cells has
      been suggested to be the cause of various human diseases, data from this study
      could have important implications for the health effects of RFR exposure.

PMID- 9261543
TI  - RF radiation-induced changes in the prenatal development of mice.
AB  - The possible effects of radiofrequency (RF) radiation on prenatal development has
      been investigated in mice. This study consisted of RF level measurements and in
      vivo experiments at several places around an "antenna park." At these locations
      RF power densities between 168 nW/cm2 and 1053 nW/cm2 were measured. Twelve pairs
      of mice, divided in two groups, were placed in locations of different power
      densities and were repeatedly mated five times. One hundred eighteen newborns
      were collected. They were measured, weighed, and examined macro- and
      microscopically. A progressive decrease in the number of newborns per dam was
      observed, which ended in irreversible infertility. The prenatal development of
      the newborns, however, evaluated by the crown-rump length, the body weight, and
      the number of the lumbar, sacral, and coccygeal vertebrae, was improved.

PMID- 9261544
TI  - The incidence and clinical significance of antibodies to interferon-a in patients
      with solid tumors.
AB  - It is well known that natural and recombinant proteins can cause antibody
      formation in the host. We have studied the incidence of binding and neutralizing
      antibodies in carcinoid patients (n = 327). All together 204 patients received
      interferon-alpha 2b (Intron-A), median does 15 MU range 9-35 MU/week
      subcutaneously and 51% of the patients developed binding antibodies by
      immunoassay and 17% showed positive neutralization assay but high titer
      antibodies (> 800 NU/ml) were only found in 4% of the patients. The median time
      until the development of binding antibodies was 26 months and neutralizing
      antibodies 25 months. Twenty-nine patients received interferon-alpha 2a
      (Roferon), median does 18 MU/week subcutaneously and 45% developed binding
      antibodies, 38% had positive neutralization assay and 28% presented high titer
      antibodies. Binding and neutralizing antibodies occurred at the same time after
      median six months of treatment. Patients treated with Wellferon (n = 45) and
      leukocyte interferon (n = 48), median dose of 15 MU/week subcutaneously did not
      develop any neutralizing antibodies. The majority of the interferon-alpha 2
      antibodies were of the IgG isotype. The clinical relevance of the development of
      high titer neutralizing antibodies was evaluated in the patients. All together 17
      patients developed high titer neutralizing antibodies and of these 12 patients
      showed loss of antitumor response measured as increased level of tumor markers
      and of tumor progression. In nine of these patients a switch to human leukocyte
      interferon reinstituted an antitumor response. Neutralizing antibodies against
      recombinant interferon-alpha 2a and 2b might occur in patients with carcinoid
      tumors. The incidence of high titer neutralizing antibodies is significantly
      higher in patients treated with interferon-alpha 2a compared to interferon-alpha
      2b. A significant number of patients lost the antitumor effect during development
      of neutralizing antibodies at high titers, but human leukocyte interferon can be
      used as rescue treatment.

PMID- 9261545
TI  - Interferon antibodies in patients with infectious diseases. Anti-interferon
      antibodies.
AB  - Interferons (IFNs) are generally recognized as the most important therapeutic
      agent in some infectious diseases such as chronic hepatitis B and C. Since the
      early clinical trials it was documented that the therapeutic use of IFNs could be
      complicated by the development of antibodies able to neutralize or to bind to the
      IFN molecule. After several years of research it is now widely accepted that the
      presence of circulating anti-IFN antibodies may affect the response to IFN. Here
      we summarize what is currently know on the clinical significance of antibodies to
      IFN in IFN-treated viral diseases patients.

PMID- 9261546
TI  - Treatment-induced antibodies to interleukin-2.
AB  - Interleukin-2 (IL-2) is a 15 kDa glycoprotein with proven activity as an immune
      stimulant in the treatment of malignant disorders, congenital and acquired immune
      deficiencies, infectious disorders, and as an adjuvant to vaccines. Both natural
      and recombinant type IL-2 preparations have been applied in clinical treatment
      trials and have turned out to be immunogenic, although to a varying extent.
      Enzyme immunoassays and western blotting are standard procedures for the
      detection of IL-2-binding antibodies, whereas the neutralizing capacity of these
      antibodies is frequently demonstrated by inhibition of IL-2-dependent cell growth
      in vitro. The rate of treatment-induced IL-2 antibodies has varied from 0% to
      100% in reported trials and frequently exceeded 50% in patients exposed to
      recombinant IL-2, whereas natural type IL-2 appeared to be little immunogenic.
      Duration of treatment, cumulative IL-2 dose, and route of IL-2 administration are
      likely to determine both the rate of seroconversion as well as composition and
      properties of the anti-IL-2 antibodies. Interleukin-2 antibodies are polyclonal
      in nature and predominantly composed of IgM and IgG types. Frequently they react
      with both recombinant and natural IL-2 types. As a rule, neutralizing IL-2
      antibodies are detected in serum samples with high IL-2-binding titers and are
      recognized later than their non-neutralizing predecessors. Neutralization in
      vitro, however, does not predict neutralization in vivo, and there are very rare
      patients with documented, antibody-mediated loss of response to IL-2 treatment.
      More frequently, IL-2 antibodies will limit the expression of IL-2-dependent
      proteins in vivo, but the opposite has also been observed. Although the precise
      mechanism of antibody induction by IL-2 is unknown, immunogenicity of some drug
      formulations rather than polyclonal B-cell activation appears to play a critical
      role. Approaches aiming at limiting the immunogenicity of IL-2 preparations are
      discussed, and strategies how to recognize and circumvent antibody-mediated IL-2
      resistance are presented.

PMID- 9261547
TI  - Natural antibodies to IL-2.
AB  - Natural antibodies to human interleukin-2 are present in sera of patients
      infected with human immunodeficiency virus and also, at a lower titre, in sera of
      healthy individuals. These antibodies could be purified by affinity
      chromatography. Purified human anti-hIL-2 antibodies can interfere with
      lymphocyte proliferation both in the lymphokine activated killer cell assay and
      in the mixed lymphocyte culture. The neutralizing activity observed in vitro
      suggests that these antibodies play a role in the elaborate cytokine network by
      which the immune system regulates its response.

PMID- 9261548
TI  - Natural antibodies to interferon-gamma.
AB  - Natural antibodies to interferon (IFN)-gamma were detected in the serum of virus
      infected patients and also, at a low titre, in the serum of healthy subjects. The
      increased titre of antibodies to IFN-gamma in the sera of virus-infected
      patients, and its decrease with clinical resolution, indicate that these
      antibodies are related to viral infection and probably reflect IFN-gamma
      production as a result of antigenic stimulation in vivo. Natural antibodies to
      IFN-gamma were affinity purified and studied for their capability to interfere in
      vitro with the multiple activities of the lymphokine. Data obtained show that
      these human anti-IFN-gamma antibodies have no inhibitory effect on the antiviral
      and antiproliferative activity of IFN-gamma and do not interfere with the binding
      of the lymphokine to its specific cell receptor. Instead, they can inhibit the
      expression of HLA-DR antigens induced by IFN-gamma on U937 cells and interfere,
      in mixed lymphocyte culture, with the proliferation of lymphocytes and the
      generation of cytotoxic lymphocytes. Experiments in animal models suggest that
      natural antibodies to IFN-gamma may have a role in the immunoregulatory process
      limiting the intensity and/or duration of immune response. As they can interfere
      only with the immunomodulating activities of IFN-gamma, these antibodies might
      open up new therapeutic approaches to diseases with evidence of activated cell
      mediated immunity.

PMID- 9261549
TI  - Anti-cytokine autoantibodies: epiphenomenon or critical modulators of cytokine
      action.
AB  - Low amounts of high-affinity autoantibodies to various cytokines have been
      detected in sera from healthy donors. Their levels, although highly variable, are
      increased in the circulation of patients subjected to cytokine therapy or
      suffering from a variety of immunoinflammatory diseases. It has been suggested
      that these autoantibodies play a regulatory role in the intensity and duration of
      an immune response. The antibodies may prevent the binding of a cytokine to its
      specific cell surface receptor thereby neutralizing its biological activity in
      vivo. They may also act as carrier proteins preventing the rapid elimination of a
      cytokine from the circulation and thus increase its bioactivity. Additionally or
      alternatively, autoantibodies may modulate cytokine-induced intracellular signal
      transduction pathways or trigger complement-mediated cytotoxicity towards cells
      carrying membrane-bound cytokines. The autoantibodies may exert their regulatory
      role in compliance with the other factors that control cytokine activity,
      including soluble cytokine receptors, cell surface decoy receptors, and receptor
      antagonists. Although not favored by many investigators, a less sophisticated
      role for naturally occurring anti-cytokine autoantibodies should be considered as
      well. Recent evidence has shown that autoantibodies are generated at a high
      frequency as part of a response to foreign antigens. These antibodies are
      produced by B cells arising from the process of somatic mutation. Thus anti
      cytokine autoantibodies may be the result of a "leaky" B cell response triggered
      by immunoinflammatory processes. High-titered autoantibodies induced by cytokine
      therapy are of clinical concern since their occurrence is often associated with
      the loss of response to treatment. Moreover, they may also neutralize
      endogenously produced cytokines with possible pathological consequences. In this
      paper we have reviewed the available information on the biological and clinical
      significance of both naturally occurring and therapeutically induced anti
      cytokine autoantibodies in animals and man with the emphasis on antibodies
      directed to interferons.

PMID- 9261550
TI  - Potential therapeutic use of antibodies directed towards HuIFN-gamma.
AB  - IFN-gamma is an important regulator of immune responses and inflammation. Studies
      in animal models of inflammation, autoimmunity, cancer, transplant rejection and
      delayed-type hypersensitivity have indicated that administration of antibodies
      against IFN-gamma can prevent the occurrence of diseases or alleviate disease
      manifestations. Therefore, it is speculated that such antibodies may have
      therapeutical efficacy in human diseases. Since animal-derived antibodies are
      immunogenic in patients several strategies are being developed in order to reduce
      or abolish this human anti-mouse antibody (HAMA) response. In our laboratory, we
      have constructed a single-chain variable fragment (scFv) derived from a mouse
      antibody with neutralizing potential for human IFN-gamma. A scFv consists of only
      variable domains tethered together by a flexible linker. The scFv was
      demonstrated to neutralize the antiviral activity of HuIFN-gamma in vitro and
      therefore might be considered as a candidate for human therapy.

PMID- 9261551
TI  - Structure-activity of type I interferons.
AB  - Type I IFNs constitute a family of proteins exhibiting high homology in primary,
      secondary, and tertiary structures. They interact with the same receptor and
      transmit signals to cellular nucleus through a similar mechanism, eliciting
      roughly homogeneous biological activity. Nevertheless, the members of that
      family, IFN alpha species, IFN beta and IFN omega, due to local differences in
      the structure sometime show distinct properties. From the reported data it
      results that even minute changes or differences in the primary sequences could be
      responsible for a significant variety of biological actions, thus inducing to the
      hypothesis that Type I IFNs, rather than to be the result of a redundant
      replication during the evolution play definite roles in the defense of living
      organisms to foreign agents.

PMID- 9261552
TI  - Measurement of cytokine antibodies. Test development.
AB  - Several assays have been used for detection of antibodies against cytokines. The
      choice of assay is greatly dependent on the intended goal, e.g. detection of
      naturally occurring antibodies or therapy induced antibodies. The different
      assays can be grouped in 2 categories. The interference or indirect assays are
      based on the detection of the test sample interference with the biological
      activity, with detection of the cytokine in EIA or with binding to cellular
      receptors. In direct assays cytokine antibodies are detected by binding to solid
      phase fixed cytokines, followed by incubation with a secondary enzyme-labelled
      anti-human Ig antibody or by binding to 125I-labelled cytokines in RIA.

PMID- 9261553
TI  - The expression of potency of neutralizing antibodies for interferons and other
      cytokines.
AB  - The occurrence of antibody formation in patients administered biologically active
      human proteins as biotherapy for different diseases emphasizes the importance of
      establishing a common method of reporting neutralizing antibody levels for such
      cytokines. For quantitative neutralization bioassays, the preferred expression of
      the neutralizing potency of an antiserum is a titer, that is, the dilution of
      serum that reduces 10 Laboratory Units (LU)/ml of the cytokine to 1 Laboratory
      Unit/ml, the endpoint of most bioassays. This 10-to-1 LU/ml expression, which has
      been recommended by the World Health Organization for recording the results of
      interferon neutralization by the constant interferon method (with varying
      dilutions of serum) can also be used with the constant antibody method (with
      varying concentrations of interferon). For various reasons, interferon doses in
      International Units (IU)/ml should not be used for the neutralization test.
      Should the interferon concentration vary, intentionally or otherwise, from the
      intended dose of 10 LU/ml, a simple calculation allows expression of the
      neutralizing potency as the recommended reduction of 10-to-1 LU/ml as follows:
      the titer to be reported is the reciprocal of the antibody dilution (achieving
      the endpoint), multiplied by the interferon concentration (measured in that day's
      titration) minus one, divided by 9. This index of neutralization is the preferred
      method to represent the neutralizing potency of polyclonal and monoclonal
      antibodies and should make the results from different laboratories more readily
      interpretable and enable comparison.

PMID- 9261554
TI  - Evolution of nerve development in frogs. I. The development of the peripheral
      nervous system in Discoglossus pictus (Discoglossidae).
AB  - The gross anatomical development of the peripheral nervous system (PNS) during
      embryogenesis and metamorphosis in the frog Discoglossus pictus is described
      based on whole-mount immunostaining for nerves and muscles. In the head, neurite
      outgrowth starts with the mandibular ramus of the trigeminal nerve at the tailbud
      stage. Cranial muscles are innervated as soon as they differentiate, beginning at
      mid-embryonic stages. During late embryonic stages, the course of the trigeminal
      and facial nerves becomes greatly distorted and changes again drastically during
      metamorphosis accompanying the reorganization of the jaw muscles. Two occipital
      somites and nerves develop transitorily but degenerate at late embryonic stages.
      The hypoglossal nerve develops by fusion of the first and second spinal nerves
      and receives a transitory contribution of the third and fourth spinal nerve at
      embryonic stages. In the trunk, several classes of Rohon-Beard neurites could be
      identified at embryonic stages, one of which forms intersegmental sensory nerves
      that prefigure the course of the sensory rami of spinal nerves at later stages.
      We give detailed schedules of PNS and cranial muscle development which, in
      comparison with data on other frog species described in a companion paper, will
      serve as a basis to evaluate heterochronic shift during evolution of PNS
      development in frogs.

PMID- 9261555
TI  - Evolution of nerve development in frogs. II. Modified development of the
      peripheral nervous system in the direct-developing frog Eleutherodactylus coqui
      (Leptodactylidae).
AB  - We use whole-mount immunohistochemistry to describe the pattern of development of
      cranial nerves and muscles in the direct-developing leptodactylid frog
      Eleutherodactylus coqui. Comparison with nerve development in the biphasically
      developing frogs Physalaemus pustulosus (Leptodactylidae) and Discoglossus pictus
      (Discoglossidae; described in a companion paper) allows us to infer the ancestral
      leptodactylid ontogenetic pattern and the extent to which it has been modified
      during the evolution of direct development in Eleutherodactylus. While early
      embryonic development of cranial nerves and muscles is remarkably conserved in E.
      coqui, most transitory embryonic and larval characters (e.g., occipital and
      spinal myotomes together with their innervation, the distorted course of
      trigeminal and facial nerves, ventral branchial arch muscles, a subset of
      branchial-nerve rami and the lateral-line system) never develop. However, a few
      larva-typical characters are recapitulated, including Rohon-Beard cells and an
      anastomosis between the vagal and hypoglossal nerve. In addition to the
      abbreviation of ontogeny by loss of larva-specific traits, dramatic dissociations
      and heterochronic shifts of characters can be observed in E. coqui. The onset of
      development of limb and trunk innervation has been pre-displaced to early
      embryonic stage. Moreover, the reorientation of cranial muscles and nerves
      corresponding to late metamorphic events in biphasically developing anurans
      occurs relatively much earlier and is less pronounced in E. coqui resulting in an
      extreme condensation of ontogeny.

PMID- 9261556
TI  - Professor Lu Ji Shi.

PMID- 9261557
TI  - Replication of M13 single-stranded DNA bearing a site-specific ethenocytosine
      lesion by Escherichia coil cell extracts.
AB  - Previous investigation on the mutagenic effects of 3, N4-Ethenocytosine (epsilon
      C), a nonpairing DNA lesion, revealed the existence of a novel SOS-independent
      inducible mutagenic mechanism in E. coli termed UVM for UV modulation of
      mutagenesis. To investigate whether UVM is mediated by an alteration of DNA
      replication, we have set up an in vitro replication system in which phage M13
      viral single-stranded DNA bearing a single site-specific (epsilon C) residue is
      replicated by soluble protein extracts from E. coli cells. Replication products
      were analyzed by agarose gel electrophoresis and the frequency of translesion
      synthesis was determined by restriction endonuclease analyses. Our data indicate
      that DNA replication is strongly inhibited by epsilon C, but that translesion DNA
      synthesis does occur in about 14% of the replicated DNA molecules. These results
      are very similar to those observed previously in vivo, and suggest that this
      experimental system may be suitable for evaluating alterations in DNA replication
      in UVM-induced cells.

PMID- 9261558
TI  - Human chromosome pellicle antibody recognizing centromere protein-C (CENP-C), the
      main component of the kinetochore.
AB  - Recently the antichromosome antisera from several scleroderma patients have been
      found to recognize the pellicle of metaphase and anaphase chromosomes. In order
      to identify the pellicle components, we used these antichromosome antisera to
      screen a human embryonic cDNA library. The sequences of the positive clones are
      identical to the cDNA gene sequence of CENP-C (centromere protein C), a human
      centromere autoantigen. This result suggests that CENP-C is a component of the
      pellicle of human metaphase and anaphase chromosomes.

PMID- 9261559
TI  - Increment of hFIX expression with endogenous intron 1 in vitro.
AB  - This paper probes into the feasibility of increasing expression level of hFIX
      gene with endogenous intron 1 sequence. hFIX minigene was obtained with middle
      sequence truncated intron 1 inserted into the relative site of hFIX cDNA, and
      plasmid vector pKG5i'IX, retroviral vector GINaCi'IX were constructed. These
      vectors were transduced into target cells of PA317, C2C12, primary rabbit skin
      fibroblasts (RSF) and primary human skin fibroblasts (HSF). The expression level
      of mixed colonies are PA317/pKGoi'IX, 151 ng/10(6) cells/24h; PA317/G1NaCi'IX,
      308 ng/10(6) cells/24 h; C2C12/G1 NaCi'IX, 188 ng/10(5) cells/24 h;
      RSF/G1NaCi'IX, 1929 ng/10(5) cells/24 h; HSF/G1NaCi'IX, 1646 ng/10(6) cells/24 h.
      These results indicated that hFIX minigene with intron 1 is able to increase the
      expression level to about 3 times of that of hFIX cDNA. Meanwhile, in order to
      study the application of hFIX minigene in the retroviral-mediated gene transfer
      system and refrain from intron splicing during viral production, a retroviral
      vector G1NaCi'IXR with reversely inserted hFIX minigene expression cassette was
      constructed. The expression level of reverse constructor in PA317 cells was 390
      ng/10(6) cells/24 h with 79% of bioactivity. PCR detection of HT/G1NaCi'IXR cells
      infected with PA317/G1NaCi'IXR supernatant confirmed the existence of intron 1
      sequence. These results suggested that expression vector with forward-inserted
      intron1-carrying hFIX expression cassette can be used in directed gene transfer,
      but when using the retroviral-mediated gene transfer system, reversely-inserted
      intronl-carrying hFIX expression cassette should be considered.

PMID- 9261560
TI  - Cytological identification of an isotetrasomic in rice and its application to
      centromere mapping.
AB  - The aneuploid with isochromosome or telochromosome is ideal material for
      exploring the position of centromere in lingkage map. For obtaining these
      aneuploids in rice, the primary trisomics from triplo-1 to triplo-12 and the
      aneuploids derived from a triploid of indica rice variety Zhongxian 3037 were
      carefully investigated. From the offsprings of triplo-10, a primary trisomic of
      chromosome 10 of the variety, an isotetrasomic "triplo-10-1" was obtained.
      Cytological investigation revealed that a pair of extra isochromosomes of triplo
      10-1 were come from the short arm of chromosome 10. In the offsprings of the
      isotetrasomic, a secondary trisomic "triplo-10-2", in which the extra- chromosome
      was an isochromosome derived from the short arm of chromosome 10, was identified.
      With the isotetrasomic, secondary trisomic, primary trisomic and diploid of
      variety Zhongxian 3037, different molecular markers were used for exploring the
      position of the centromere of chromosome 10. Based on the DNA dosage effect, it
      was verified that the molecular markers G1125, G333 and L169 were located on the
      short arm, G1084 and other 16 available molecular markers were on the long arm of
      chromosome 10. So the centromere of chromosome 10 was located somewhere between
      G1125 and G1084 according to the RFLP linkage map given by Kurata et al[1]. The
      distance from G1125 to G1084 was about 3.2 cM.

PMID- 9261561
TI  - High efficiency DNA delivery into swine oocytes and embryos by electronic pulse
      delivery (EPD).
AB  - The production of transgenic swine for xenotransplantation has been proposed as
      an optimal option to overcome the chronic shortage of human organ donors.
      Generation of genetically engineered swine has been elusive due to the
      difficulties in gene transfer. In order to achieve effective gene delivery, a key
      step for the genetic modification, we applied electronic pulse delivery (EPD)
      technology to introduce H2Kb-DC DNA construct into swine eggs. Using the
      developed EPD Protocols, we have achieved good viability of the EPD treated
      oocytes, satisfactory embryonic development of the EPD treated embryos, and
      stable DNA transfer into the swine embryos with high efficiency. Thus,
      application of the EPD technology promises to effectively facilitate the
      generation of large transgenic mammals.

PMID- 9261562
TI  - Identification and expression of epidermal growth factor gene in mouse testis.
AB  - Epidermal growth factor (EGF) is produced primarily by Leydig cells of human
      testis. Expression of the EGF gene was assessed in mouse testis during the course
      of sexual maturation by the application of the RT-PCR method and the use of
      specific oligonucleotide primers. Testis EGF mRNA content increased with the
      developmental age of the mice, i.e., day 15 < day 30 < day 45 postnatal. The
      expression of the EGF gene appears to correlate with maturation of the testis and
      proliferation of Leydig-cells.

PMID- 9261563
TI  - Characterization of 5'-proximal sequence of mouse GABA transporter gene (GAT-1).
AB  - The cDNA molecule encoding the mouse GABA transporter gene (GAT-1) was used as
      probe for selecting GAT-1 gene from mouse genomic library. A positive clone,
      harboring the whole open reading frame of the GAT-1 protein and designated as
      MGABAT-G, was fished out from the library, the 5' proximal region and intron 1
      were sequenced and analysed, and low homology was found in the above region
      between GAT-1 genes from mouse and human except some short conserved sequences.
      The DNA-protein interactions between DNA fragments containing the conserved
      sequences in the 5' proximal region and nuclear proteins from different tissues
      of mouse were studied by means of gel-shift assay, and Southern-Western blot. The
      results indicate a possible positive-negative regulation mode controlling the
      expression of the mouse GAT-1 gene.

PMID- 9261564
TI  - Molecular characterization and functional expression of opioid receptor-like1
      receptor.
AB  - The opioid receptor-like1 receptor (ORL1), an orphan receptor whose human and
      murine complementary DNAs, has been characterized recently. ORL1 transcripts are
      particularly abundant in the central nervous system. We demonstrated that ORL1
      expressed in human neuroblastoma SK-N-SH and SH-SY5Y cell lines by radioligand
      binding assay, reverse transcription polymerase chain reaction (RT-PCR) and
      Northern analysis in the present study. Stimulation with ORL1 specific agonist,
      nociceptin/orphanin FQ, increased [35S]GTP gamma S binding to SK-N-SH cell
      membranes (EC50 = 14 +/- 0.45 nM), and attenuated forskolin-stimulated
      accumulation of cellular cAMP (EC50 = 0.80 +/- 0.45 nM), indicative that
      activation of ORL1 activates G proteins and inhibits adenylyl cyclase. Activation
      of ORL1 receptor was also accessed using CHO:hORL1 cell line by microphysiometer.
      Treatment of nociceptin/orphanin FQ increased extracellular acidification rate
      significantly.

PMID- 9261566
TI  - The apoptosis of HEL cells induced by hydroxyurea.
AB  - Hydroxyurea has been used to synchronize cultured cells to S-phase and used to
      treat patients with sickle-cell anemia. Recently, we found that hydroxyurea can
      induce the apoptosis of HEL (human erythroleukemia) cells. The induced HEL cells
      showed ultrastructurally chromatin condensation with regular crescents at the
      nuclear edges and apoptotic bodies. However, the cells of K562, another human
      erythroleukemia cell line, did not show such morphological changes. Under
      fluoroscope, the HEL cells after induction often displayed a clear reduction in
      nuclear diameter and nuclear chromatin cleavage and condensation and the presence
      of nuclear ring and apoptotic bodies. Analysis with flow cytometry showed that
      the percentage of apoptotic cells is about 30-40% after HEL cells were induced by
      hydroxyurea for 3 days. DNA ladder can be observed by electrophoretic analysis.

PMID- 9261565
TI  - Differential expression of a cDNA clone in human liver versus hepatic cancer-
      highly homologous to aryl-dialkyl-phosphatase.
AB  - We applied the technique of mRNA differential display to normal liver tissue and
      hepatoma cell line Hep3B. One of the isolated cDNA clones was expressed in human
      normal liver tissue but not in the human hepatocarcinoma cell line. Northern Blot
      analysis confirmed that high level of mRNA was expressed in human normal liver
      tissue but the level was decreased in non-cancerous liver tissue from hepatoma
      patients. Low level or no expression was observed in human hepatoma tissue. One
      of these transcripts was about 1.8 kb in length. Southern Blot analysis showed
      that it was a single copy gene. We obtained a full length cDNA clone of 2,395 bp
      by screening human liver 5'-stretch plus cDNA library. Nucleotide sequence
      indicated that this clone was highly homologous to aryl-dialkyl-phosphatase and
      possessed two polymorphic sites. Aryl-dialkyl-phosphatase which has a prominent
      role in the metabolism of several toxic, synthetic compounds, may be potentially
      related to human hepatocarcinoma susceptibility. The biological significance of
      its differential expression in normal versus malignant tissue is discussed.

PMID- 9261567
TI  - RAPD analysis of natural populations of Acanthopanax brachypus.
AB  - Random Amplified Polymorphic DNA (RAPD) analysis is a new technology of molecular
      marking which has proved very powerful in detecting genetic diversity at the
      level of population. The genomic DNAs used in our experiment were extracted from
      fresh leaves taken from 59 individuals sampled from three natural populations in
      Yan An, Shanxi Province. Through more than 2,000 PCRs, deep-going RAPD analysis
      was carried out on DNA samples from 49 individuals. The percentage of polymorphic
      RAPD loci found in these three populations were respectively 27.2%, 18.6% and
      5.4%; the average genetic distances within population, 0.055, 0.036 and 0.008;
      the average genetic distances between populations (I-II), (I-III) and (II-III),
      0.105, 0.096 and 0.060. The genetic diversity of A. brachypus within and between
      populations was found, for the first time, to be rather poor, thus revealing
      innate factors as the cause contributing to its endangered status. In addition,
      our work also provides basic materials for elucidating the underlying cause of
      its endangerment and for its protection biology.

PMID- 9261568
TI  - Association of DNA with nuclear matrix in in vitro assembled nuclei induced by
      rDNA from Tetrahymena shanghaiensis in Xenopus egg extracts.
AB  - The nuclei assembled from exogenous DNA or chromatin in egg extracts resemble
      their in vivo counterparts in many aspects. However, the distribution pattern of
      DNA in these nuclei remains unknown. We introduced rDNA from the macronuclei of
      Tetrahymena into Xenopus cell-free extracts to examine the association of
      specific DNA sequences with nuclear matrix (NM) in the nuclei assembled in vitro.
      Our previous works showed the 5'NTS (non-transcription sequences) of the rDNA
      specifically bind to the NM system in the macronuclei. We show now the rDNA could
      induce chromatin assembly and nuclear formation in Xenopus cell-free system. When
      we extracted the NM system and compared the binding affinity of different regions
      of rDNA with the NM system, we found that the 5'NTS still hold their binding
      affinity with insoluble structure of the assembled nuclei in the extracts of
      Xenopus eggs.

PMID- 9261569
TI  - From free chromatin analysis to high resolution fiber FISH.

PMID- 9261570
TI  - The global pattern of cytochrome oxidase stripes in visual area V2 of the macaque
      monkey.
AB  - In primate visual area V2, histochemical staining for cytochrome oxidase (CO)
      reveals a tripartite pattern of densely labeled thick and thin stripes separated
      by pale interstripes. This modularity is believed to be related to functionally
      distinct processing streams that course through the hierarchy of visual areas.
      Here, we studied the overall pattern of CO stripes in V2 of the macaque monkey,
      using tissue that had been physically unfolded and flattened prior to
      histological sectioning. CO stripes were identified on the basis of their
      physical dimensions and on their differential immunoreactivity for the monoclonal
      antibody Cat-301. We observed several distinctive features of compartmental
      organization in V2. The most prominent was a dorso-ventral asymmetry in the
      stripe pattern, occurring in the majority of cases studied. In dorsal V2, most
      stripes measure approximately 10 mm in length and run roughly orthogonal to both
      the posterior and anterior borders of V2. In contrast, many stripes in ventral V2
      have a curved or oblique trajectory, and some extend up to 20 mm in length.
      Stripes following a curved trajectory often become nearly parallel to the
      anterior border of V2. These differences imply an asymmetry in how the visual
      field maps onto dorsal versus ventral stripes. Occasionally, thin stripes fail to
      alternate with thick stripes but instead occur next to one other, separated only
      by interstripes. In three most complete reconstructions, we found that unfolded
      V2 is approximately 110 mm in length, approximately 900 mm2 in surface area, and
      that it contains approximately 28 complete sets of stripes (one thick, one thin
      and two interstripes), yielding an average of approximately 4 mm per set of
      stripes. The maximum width of ventral V2 (13-14 mm) exceeds that of dorsal V2 (10
      mm), and there is a consistent narrowing of V2 in the region of foveal
      representation (3-5 mm).

PMID- 9261571
TI  - The organization of pyramidal cells in area 18 of the rhesus monkey.
AB  - The aim of this study was to investigate the vertical organization of axons and
      pyramidal cells in area 18, and to compare it with that in area 17. In area 18
      there are regularly spaced vertical bundles of myelinated axons that have an
      average center-to-center spacing of 21 microns. This arrangement of axons
      resembles that in area 17. Pyramidal cells in area 18 and their apical dendrites
      are less regularly arranged. The apical dendrites of the pyramidal cells of layer
      6A aggregate with those from layer 5 pyramids to form swathes of apical dendrites
      that pass into layer 4. There they are joined by the apical dendrites of the
      small layer 4 pyramids, so that much of the neuropil of layer 4 is occupied by
      apical dendrites. Most of these apical dendrites form their terminal tufts in
      layer 3. Very few of them reach layer 1, which is dominated by the apical
      dendrites of layer 2/3 pyramids. Thus, there are two tiers of apical dendrites
      and their apical tufts, a deep one formed by the layer 4, 5 and 6 apical
      dendrites that terminate in layer 3, and a second one formed by the apical
      dendrites of layer 2/3 pyramids that terminate in layer 1. In contrast, in area
      17 the apical dendrites of layer 5 pyramids form discrete clusters that have a
      center-to-center spacing of 23 microns. These clusters are joined by the apical
      dendrites of the layer 2/3 pyramids and all of these apical dendrites form their
      apical tufts in layer 1. Based upon the dispositions of the apical dendrites of
      the pyramidal cells in area 17 and 18, we speculate that the influences of, and
      the interactions between, the feed-forward and feed-back signals in the two areas
      are quite different, because in the two areas different postsynaptic targets are
      available to these afferents.

PMID- 9261572
TI  - Neuronal composition and morphology in layer IV of two vibrissal barrel subfields
      of rat cortex.
AB  - The technique of intracellular injection in fixed, flattened slices was used to
      study neuronal composition and morphology in the postero-medial barrel subfield
      (PMBSF) and the antero-lateral barrel subfield (ALBSF) in layer IV of rat cortex.
      The PMBSF and the ALBSF contain the cortical representation of the mystacial and
      rostral snout vibrissae respectively. Neuronal composition differed between the
      PMBSF and the ALBSF. Modified pyramidal cells were the most numerous neuronal
      type in the PMBSF (73.1%), whereas spiny multipolar (stellate) neurons were the
      most numerous type in the ALBSF (40.9%). Tangential dendritic field areas of
      modified pyramidal cells and spiny multipolar cells in the barrels of the two
      barrel subfields were compared. Dendritic field areas of spiny multipolar neurons
      located in the barrels of the PMBSF and the ALBSF were similar (mean +/- SD; 2.44
      +/- 1.83 x 10(4) and 2.88 +/- 1.47 x 10(4) microns2 respectively). Likewise,
      there was no significant difference in 'basal' dendritic field area of modified
      pyramidal neurons located in the barrels of the two different barrel subfields
      (4.63 +/- 1.96 x 10(4) and 4.45 +/- 1.81 x 10(4) microns2 for PMBSF and ALBSF
      respectively). The mean cross-sectional area of PMBSF barrels (20.5 +/- 5.69 x
      10(4) microns2) in which neurons were injected was approximately seven times
      larger than that of the ALBSF (2.94 +/- 1.46 x 10(4) microns2). Thus, on average,
      the dendritic territories of these two neuronal classes sample a larger
      proportion of the cross-sectional area of the barrels in the ALBSF than in the
      PMBSF. We conclude that the close relationship between basal dendritic field area
      of supragranular pyramidal neurons and module size, reported in studies of other
      sensory areas, is not evident in all barrel subfields of the rat.

PMID- 9261573
TI  - The occipitoparietal pathway of the macaque monkey: comparison of pyramidal cell
      morphology in layer III of functionally related cortical visual areas.
AB  - The dendritic morphology of pyramidal cells located at the base of layer III in
      the primary visual area (V1), the second visual area (V2), the middle temporal
      area (MT), the ventral portion of the lateral intraparietal area (LIPv) and in
      the portion of cytoarchitectonic area 7a within the anterior bank of the superior
      temporal sulcus was revealed by injecting neurons with Lucifer Yellow in fixed,
      flattened slices of macaque monkey visual cortex. These areas correspond to
      different levels of the occipitoparietal cortical 'stream', which processes
      information related to motion and spatial relationships in the visual field. The
      tissue was immunocytochemically processed to obtain a light-stable
      diaminobenzidine reaction product, revealing the dendritic morphology in fine
      detail. Retrogradely labelled MT-projecting neurons in supragranular V1 (layer
      IIIc of Hassler's nomenclature, corresponding to Brodmann's layer IVb) were
      predominantly pyramidal, although many spiny multipolar (stellate) cells were
      also found. The average basal dendritic field area of pyramidal neurons in
      sublamina IIIc of V1 was significantly smaller than that in the homologous layer
      of V2, within the cytochrome oxidase-rich thick stripes. Furthermore, the average
      basal dendritic field areas of V1 and V2 pyramidal neurons were significantly
      smaller than those of neurons in MT, LIPv and area 7a. There was no difference in
      basal dendritic field area between layer III pyramidal neurons in areas MT, LIPv
      and 7a. While the shape of most basal dendritic fields was circularly symmetrical
      in the dimension tangential to the cortical layers, there were significant biases
      in complexity, with dendritic branches tending to cluster along particular axes.
      Sholl analysis revealed that the dendritic fields of neurons in areas MT, LIPv
      and 7a were significantly more complex (i.e. had a larger number of branches)
      than those of V1 or V2 neurons. Analysis of basal dendritic spine densities
      revealed regional variations along the dendrites, with peak densities being
      observed 40-130 microns from the cell body, depending on the visual area. The
      peak spine density of layer III pyramidal neurons in V1 was lower than that
      observed in V2, MT or LIPv, which were all similar. Pyramidal neurons in area 7a
      had the greatest peak spine density, which was on average 1.7 times that found in
      V1. Calculations based on the average spine density and number of dendritic
      branches at different distances from the cell body demonstrated a serial increase
      in the total number of basal dendritic spines per neuron at successive stations
      of the occipitoparietal pathway. Our observations, comparing dendritic fields of
      neurons in the homologous cortical layer at different levels of a physiologically
      defined 'stream', indicate changes in pyramidal cell morphology between
      functionally related areas. The relatively large, complex, spine-dense dendritic
      fields of layer III pyramidal cells in rostral areas of the occipitoparietal
      pathway allow these cells to sample a greater number of more diverse inputs in
      comparison with cells in 'lower' areas of the proposed hierarchy.

PMID- 9261574
TI  - Cerebral microgyria, thalamic cell size and auditory temporal processing in male
      and female rats.
AB  - Induction of microgyria by freezing injury to the developing somatosensory cortex
      of neonatal rats causes a defect in fast auditory processing in males, but not in
      females. It was speculated that early damage to the cortex has sexually dimorphic
      cascading effects on other brain regions mediating auditory processing, which can
      lead to the observed behavioral deficits. In the current series of experiments,
      bilateral microgyri were induced by placement of a freezing probe on the skulls
      of newborn male and female rats, and these animals were tested in adulthood for
      auditory temporal processing. Control animals received sham surgery. The brains
      from these animals were embedded in celloidin, cut in the coronal plane and the
      following morphometric measures assessed: microgyric volume, medial geniculate
      nucleus (MGN) volume, cell number, and cell size, and, as a control, dorsal
      lateral geniculate nucleus (dLGN) volume, cell number and cell size. There were
      no sex differences in the cortical pathology of lesioned animals. However,
      microgyric males had more small and fewer large neurons in the MGN than their
      sham-operated counterparts, whereas there was no difference between lesioned and
      sham-operated females. There was no effect on dLGN cell size distribution in
      either sex. Microgyric males were significantly impaired in fast auditory
      temporal processing when compared to control males, whereas lesioned females
      exhibited no behavioral deficits. These results suggest that early injury to the
      cerebral cortex may have different effects on specific thalamic nuclei in males
      and females, with corresponding differences in behavioral effects.

PMID- 9261576
TI  - The Cortical Scholar Prize: Dr Adam H. Gazzaley.

PMID- 9261575
TI  - Bilateral activation of fronto-parietal networks by incrementing demand in a
      working memory task.
AB  - Working memory (WM) is known to activate the prefrontal cortex. In the present
      study we hypothesized that when additional contingencies are added to the
      instruction of a WM task, this would increase the WM load and result in the
      activation of additional prefrontal areas. With positron emission tomography we
      measured regional cerebral blood flow in nine subjects performing a control task
      and two delayed matching to sample tasks, in which the subjects were matching
      colours and patterns to a reference picture. The second of the two delayed
      matching tasks had a more complex instruction than the first, with additional
      contingencies of how to alternate between the matching of colours and patterns.
      This task thus required the subjects not only to remember a stimulus to match but
      also to perform this matching according to a specified plan. Both delayed
      matching tasks activated cortical fields in the middle frontal gyrus, the frontal
      operculum, upper cingulate gyrus, inferior parietal cortex and cortex lining the
      intraparietal sulcus, all in the left hemisphere. When alternated delayed
      matching was compared to simple delayed matching, increases were located in the
      right superior and middle frontal gyrus and the right anterior inferior parietal
      cortex. The increased demand during alternated matching thus resulted in
      bilateral activation of both dorsolateral prefrontal and inferior parietal
      cortex. The area in the inferior parietal cortex has previously been coactivated
      with the dorsolateral prefrontal cortex in several WM tasks, irrespective of the
      sensory modality of the stimuli, and during tasks involving planning.

PMID- 9261577
TI  - The Cortical Explorer Award: Dr Tom Carmichael.

PMID- 9261578
TI  - Cortical Discoverer Prize: Dr Edward White.

PMID- 9261579
TI  - Animal models for intra-abdominal infection.
AB  - Animal models are widely used to study intra-abdominal infections. Experimental
      intra-abdominal infections. Experimental intra-abdominal infection is a bi-phasic
      process; initially a peritonitis or septic phace caused by E. coli and later a
      chronic-abscess forming stage, caused by B. fragilis similar to human beings.
      Various methods have been described. These methods includes challenge of the
      peritoneum with either endogenous bacteria or inoculation of pure bacteria or
      fectal material. Non-bacterial models have also been described. Each of these
      models have their own advantages and disadvantages. The aim and the end points
      should govern the selection of the right model to be used for experimental
      purposes. The ideal model should be reliable, standard, reproducible and
      resembling human disease. A single model with those specifications is yet to be
      described.

PMID- 9261580
TI  - Peritonitis: pathophysiology and local defense mechanisms.
AB  - The peritoneal cavity can be divided in the supracolic infracolic and paracolic
      spaces, the lesser sack and the pelvis. The peritoneum is a semipermeable
      membrane which allows a flux of solutes into and from the peritoneal cavity. In
      addition, particles can be absorbed through the stomata of the diaphragmatic
      peritoneum. Secondary peritonitis is always a polymicrobial infection. The flora
      consists of aerobic enterobacteriaeceae and anaerobs mainly B. fragilis. These
      two groups of bacteria act synergistically. Besides unspecific defence
      mechanisms, i.e. the direct absorption of bacteria and the entrapment of bacteria
      in fibrin, the immunological defence mechanisms of the peritoneal cavity are
      triggered by endotoxin contained in the cell wall of the invading bacteria
      leading to the production of cytokines by macrophages, activation of complement
      and as a result the migration of granulocytes from the intervascular space into
      the peritoneal cavity.

PMID- 9261582
TI  - Antibiotics for prophylaxis and treatment of intra-abdominal infections.

PMID- 9261581
TI  - Prognostic indices in peritonitis.
AB  - In this review an update concerning the prognostic factors and scoring systems in
      peritonitis is given. The course of the disease is influenced by the
      physiological reserve of the patient, the acute severity and the type of the
      disease, the success of the operation and subsequent management and
      complications. The Acute Physiology and Chronic Health Evaluation Score (APACHE
      II) may be used with pre-operative data for the assessment of the severity of the
      disease or with postoperative data for monitoring. The Mannheim Peritonitis Index
      (MPI) and the Peritonitis Index Altona are based on pre- and intraoperative data
      and are also used for severity assessment. Treatment selection with respect to re
      operation is supported by the Prognostic Peritonitis Model and the Abdominal Re
      operation Predictive Index, covering data from the pre-, intra- and postoperative
      period. Adequate evaluation data are available for APACHE II and MPI, showing
      that these instruments are useful for risk assessment, definition of
      inclusion/exclusion criteria and analysis of comparability in clinical trials.
      Evaluation of treatment policies and quality assurance can best be performed with
      APACHE II, monitoring with APACHE II and Multiple Organ Failure scores. Support
      of individual patient care is still experimental.

PMID- 9261583
TI  - Septic complications after biliary tract stone surgery: a review and report of
      the European prospective study.
AB  - We report a prospective, controlled study of the incidence of septic
      complications following biliary tract stone surgery. This study included a total
      of 280 patients operated on in eight hospitals in various European countries. In
      this study the computer program "Surgery" was used. Of 280 patients, 77 (27.5%)
      were male and 203 (72.5%) were female. The age ranged from 20 to 92 years (mean
      54.8 years); 78.9% of the cases corresponded to clean-contaminated surgery; 85%
      of the patients received antibiotic prophylaxis with cefazolin. Twenty-one
      patients developed postoperative septic complications (7.5%) of which 12 (4.3%)
      were wound infections; five patients (1.8%) had intra-abdominal infections. The
      wound infection rate was 3.2% in clean-contaminated surgery, 7.7% in contaminated
      and 20% in dirty (p < 0.02). In laparoscopic cholecystectomy the global rate of
      septic complications was 3.6% vs. 12.6% in open cholecystectomy (p < 0.01); 2.4%
      and 6.3% wound infection respectively. The mean age of patients who developed
      postoperative septic complications was 61.5 years and 54.2 years old who did not
      develop any complications (p < 0.03). The duration of the postoperative period
      was 5 days in patients without infection and 13 days in patients with infection
      (p < 0.0001). Two patients died, one of them (0.4%) caused by sepsis. In addition
      to the European prospective study, a review of the problems of sepsis in biliary
      surgery was carried out.

PMID- 9261584
TI  - Infected pancreatic necrosis complicated by multiple organ failure.
AB  - BACKGROUND/AIMS: Sixteen patients with bacteriologically proven severe infected
      pancreatic necrosis (IPN) undergoing sequential surgical treatment were studied
      prospectively. METHODOLOGY: The severity of IPN was documented pre-operatively
      using the following scores: 1) degree of necrosis by CT scan [< 30% in three
      patients (19%); 30-50% in nine patients (56%); > 50% in four patients (25%)]; 2)
      Elebute and Stoner's sepsis score (16 +/- 4 points); 3) Goris' score of multiple
      organ failure (MOF) (5 +/- 2 points). Sequential surgical treatment was carried
      out by the same surgical team, as follows: 1) abdominal re-explorations through a
      zipper for the first 7-10 days; 2) open abdomen and repeated peritoneal
      debridements for the following 7-10 days; 3) continuous closed peritoneal lavage
      with multiple drainage, until resolution of infection (range: 15-85 days). No
      patient required further re-exploration. RESULTS: Mortality occurred in 3/16
      patients (19%), due to MOF in all 3 cases. The 13 survivors (81%) were discharged
      convalescent with closed abdominal wound, feeding orally, after 73 +/- 33 days,
      without fistulae. These results indicate that by treating severe IPN with the
      technique of sequential abdominal re-explorations, open drainage and continuous
      closed lavage, a low 19% mortality can be achieved. CONCLUSION: This study
      provides an assessment of the pre-operative severity of sepsis and of MOF in each
      patient with IPN: these data could facilitate future comparison of results
      obtained with other treatment modalities.

PMID- 9261585
TI  - Surgical treatment of severe intra-abdominal infection.
AB  - Intra-abdominal infection caused by a perforated hollow viscus, transmural bowel
      necrosis or pancreatic necrosis is a life-threatening illness. The cornerstone of
      surgical treatment is the elimation of the infectious focus, debridement and
      intra-operative lavage. In severe intra-abdominal infection secondary procedures,
      such as continuous postoperative peritoneal lavage or planned re-explorations are
      often done to prevent residual or recurrent infection. The patient benefit of
      these procedures in terms of morbidity and mortality is not evident. New
      therapeutic modalities such a intra-abdominal administration of fibrinolytic
      agents or anty-cytokine antibodies, which are primarily based on
      pathophysiological processes in the abdominal cavity following infection, may
      improve patient outcome.

PMID- 9261586
TI  - Survival probabilities of Pugh-Child-PBC classified patients in the euricterus
      primary biliary cirrhosis population, based on the Mayo clinic prognostic model.
      Euricterus Project Management Group.
AB  - BACKGROUND/AIMS: Estimation of prognosis becomes increasingly important in
      primary biliary cirrhosis (PBC) with advancing disease and also with regard to
      patient management. The ubiquitous used Pugh scoring for severity of disease is
      simple while the Mayo model which has been validated for survival estimates is
      more sophisticated. We wanted to investigate whether Pugh and Mayo scores
      correlate (they have 3 of 5 variables in common) and if so whether a survival
      probability based on Mayo data could be affixed on Pugh classes and scores
      obtained in the same patients. METHODOLOGY: All variables used for Mayo Clinic
      Prognostic Model (Mayo) scoring and Pugh-Child-PBC (Pugh) scoring were available
      in 143 PBC patients of the Pan European database Euricterus. Pugh scores P5-P15
      and has classes A (P5-6), B (P7-9) and C (P10-15). We subdivided P5 in P5A
      (patients with albumin > 40 g/l plus prothrombin time < or = 12 secs) and P5B
      (the other patients in P5). We designed a category Pugh Early (PE) for patients
      with P5A characteristics and bilirubin < 17 mmol/l. Mayo scores R0-R15-with 1-7
      years survival probabilities S-and has risk classes Low (L), Intermediate (Int),
      High (H) and Very High (VH). RESULTS: The estimated survival probabilities of the
      143 patients ranged from 88% at 7 years to 0% at 1 year, median 14% at 5 years.
      The Pugh and Mayo scores correlated r = 0.87 (p < 0.0001) and except age with P,
      all Mayo and Pugh variables correlated with both R and P at p < 0.0001. Survival
      in Pugh class A was median 43% at 7 years and was not different from survival in
      Mayo L+Int (p 0.58). In Pugh class B 7 years survival was 2%, not different from
      Mayo H (p 0.25). Survival in Pugh C was median 24% at 1 years and better than
      Mayo VH (p 0.02). Between P5A (survival 78% at 7 yr) and R 3-4; P5B-6 (40% at 7
      yr) and R5; P7 (22% at 7 yr) and R6; P8-11 (12% at 5 yr) and R7-8; and P12-14 (5%
      at 1 yr) and R9-10 no significant differences were found. From P8 upward there
      was a steep increase in death rate. PE has a 7 year survival of at least 89%.
      Charts of projected survival estimates for Pugh scores and classes are presented.
      CONCLUSION: It was possible (affixing Mayo to Pugh) to define 1-7 years survival
      probabilities to Pugh classes and scores for the last 7 years of the disease,
      i.e. the most important period for therapeutic decisions. These results need to
      be validated in other PBC populations.

PMID- 9261587
TI  - Unsuspected carcinoma of the gall bladder: case report of trocar-site metastasis
      following laparoscopic cholecystectomy.
AB  - Cancer of the gall bladder is a rare malignant neoplasm with an unfavourable
      prognosis. Laparoscopic surgery has brought about the emergence of possible
      neoplastic diffusion along trocar tracts in cases where unrecognized carcinoma of
      the gall bladder is present. The authors present a case of neoplastic abdominal
      diffusion discovered 4 months after laparoscopic cholecystectomy in which
      histologic examination of the surgical specimen revealed the presence of
      unrecognized carcinoma of the gall bladder.

PMID- 9261588
TI  - Bile duct hamartomas: diagnostic problems and treatment.
AB  - Biliary hamartomas are rare, benign malformations of the biliary tract, usually
      discovered at autopsy or erroneously confused with metastasis or other cystic
      hepatic lesions. For these reasons it is necessary to consider them in the
      differential diagnosis. The authors describe three cases of biliary hamartoma in
      which the definitive diagnosis was obtained only with the use of histologic
      examination which represents the only means available that can draw conclusions
      about the real nature of this lesion.

PMID- 9261589
TI  - Extended right trisegmentectomy for hilar bile duct carcinoma.
AB  - Extended right trisegmentectomy with total caudate lobectomy, extrahepatic bile
      duct resection and lymphadenectomy was performed for a 54-year-old man, who was
      diagnosed as type IV hilar bile duct carcinoma. After division of the right
      portal vein and all the portal venous branches to the caudate lobe and the left
      medial segment, the left hepatic artery and its branches to the segment II and
      III were dissected from the corresponding bile ducts to about 1 cm beyond the
      left margin of the umbilical portion of the left portal vein, where the lateral
      segmental bile ducts were divided after transection of the hepatic parenchyma.
      All bile duct margins were free from cancer microscopically. To our knowledge
      this is the first report of extended right trisegmentectomy for hilar bile duct
      carcinoma, in which the bile ducts of the left lateral segment are divided at the
      left side of the umbilical portion of the left portal vein. This technique
      facilitates making the intrahepatic bile duct stumps free from cancer. However,
      its impact on long-term survival remains to be determined.

PMID- 9261590
TI  - Auditory event-related cerebral potentials (P300) in hepatic encephalopathy-
      topographic distribution and correlation with clinical and psychometric
      assessment.
AB  - BACKGROUND/AIMS: Early cognitive disturbances in patients with cirrhosis (Ci) are
      difficult to assess. Therefore, we evaluated the role of topographic auditory
      evoked cerebral potentials (P300-EP). METHODOLOGY: Prospective longitudinal
      study. SETTING: Tertiary clinical care institution. PARTICIPANTS: 45 patients
      with cirrhosis were compared to 22 healthy subjects. MAIN OUTCOME MEASURES:
      Hepatic Encephalopathy (HE) was assessed using the clinical grading, standardized
      psychometric tests, and auditory evoked P300-EP by multichannel EEG recordings.
      RESULTS: In the patients, the mean P300 peak latency was significantly increased
      (386.7 +/- 26.7 versus 318.6 +/- 22.2 ms in controls, p < 0.00001). Even in
      patients with cirrhosis but no HE (n = 18) the P300 peak latency was abnormally
      prolonged (> 384 ms) in 8 cases (44%). In addition, P180 peak latency was
      significantly longer in patients with liver cirrhosis as compared to controls (p
      = 0.021). The maximal P300 amplitude was significantly lowered in patients with
      liver cirrhosis in the frontocentral and central cortical regions (FZ: p < 0.008;
      Cz: p < 0.04). Liver function and etiology of liver disease were not related to
      the increased peak latencies of the P300 and P180 peaks. CONCLUSIONS: P300-EP is
      a sensitive measure to detect functional cognitive impairment in cirrhotic
      patients with subclinical HE and clinically apparent HE. Typical changes include
      latency prolongation and decreased central peak amplitude. Some 40% of patients
      with no clinical evidence of HE and normal psychometric tests show abnormal
      results during P300 testing, which is likely to reflect early impairment of
      cognitive function. Auditory evoked P300 potentials are more sensitive than
      psychometric testing alone.

PMID- 9261591
TI  - Perspectives of liver cell transplantation: a review.
AB  - Liver-directed somatic gene therapy may be performed using the techniques of in
      vivo gene therapy, liver cell transplantation (HcTx) including ex vivo gene
      therapy, and liver transplantation, respectively (1). Liver transplantation has
      become a routine surgical technique in correcting liver disease. The usage of
      HcTx and in vivo gene therapy has increased and may replace liver
      transplantation, at least to some extent, in the future. HcTx involves the
      transplantation of healthy, intact hepatocytes with metabolic properties which
      are deficient in the recipient. Among its different applications, this concept
      may be used for the correction of inborn errors of liver disease and acute liver
      failure. The advantage of HcTx is that for successful gene therapy, the
      underlying primary defect does not require detailed characterization. In
      addition, HcTx is currently being-tested for ex vivo gene therapy. In this form
      of therapy, hepatocytes are isolated after surgical liver resection. The
      hepatocytes are ex vivo genetically modified, e.g. using retroviral vectors, and
      the selected modified cells are subsequently re-injected. Herein, we report the
      historical development, current status and perspectives of the concept of HcTx.

PMID- 9261593
TI  - Conservative pancreatic resection in patients with obstructive chronic
      pancreatitis.
AB  - The purpose of this paper is to present the results of our experience in using a
      conservative pancreatic resection approach in a certain group of patients
      suffering from chronic pancreatitis. From January 1988 to December 1995, 110
      patients underwent surgical therapy for chronic pancreatitis at the Hospital
      Clinic of the University of Barcelona. In 35 patients with an inflammatory mass
      at the pancreatic head, pylorus-preserving duodeno-pancreatectomy was performed.
      Forty male patients with localized focal pancreatitis at the body or tail
      underwent distal pancreatectomy and drainage of the pancreatic remnant. In 30
      patients with pancreatic ducts greater than 7 mm in diameter, side-to-side
      pancreaticojejunostomy was carried out. Five patients could not be included in
      any of these three categories because of their particular characteristics. In all
      cases, resolution of the symptoms was achieved at the mean follow-up of 18 months
      (range 12 to 21 months). No patient showed a deterioration of glucose
      homeostasis, and exocrine dysfunction was not observed. Patients with obstructive
      chronic pancreatitis by inflammatory cystic mass, short strictures or intraductal
      stones located in the central pancreas or uncinate process may be surgically
      managed with conservative pancreatic resection or extraction of the stones from
      the Wirsung duct. The jejunal interposition and pancreaticojejunal anastomosis
      achieved pain control without any deterioration of the endocrine or exocrine
      function.

PMID- 9261592
TI  - Bouveret's syndrome: case report and review of the literature.
AB  - Bouveret's syndrome, or gallstone duodenal pyloric obstruction, almost always
      presents with abdominal pain or vomiting. It occurs more commonly in females
      (65%), with a median age of 68.6 years. The diagnosis is made by endoscopy (60%),
      upper gastrointestinal series (45%) or by direct abdominal x-ray (23%). The
      syndrome is mainly treated by surgery (93%), but recently, it has also been
      treated by endoscopy or extracorporeal shock wave lithotripsy. The mortality rate
      has improved from 33%, as was the case before 1968, to 12% in recent years.
      Herein we report the case of a 79-year-old female with Bouveret's syndrome.

PMID- 9261595
TI  - Ultrasound diagnosis of "dry type" ileocecal tuberculosis: a case report.
AB  - Abdominal tuberculosis is a common curable disease in third world countries. CT
      is the most sensitive imaging technique. The purpose of this paper is to report
      the ultrasound diagnosis of a missed dry type ileocecal tuberculosis. A 40 year
      old patient was admitted to hospital for loin pain and was discharged following
      negative ultrasound and IVU tests. Symptoms recurred and a barium enema, follow
      through and abdominal CT were conducted. Barium studies were non specific and CT
      was normal. Sigmoidoscopy was negative for inflammatory bowel disease. A second
      ultrasound indicated a "coned" cecum with edematous and dilated terminal ileum. A
      diagnosis of tuberculosis was suggested. Colonoscopy showed typical lesions in
      the cecum with nodular terminal ileum. Biopsies were supportive of a tuberculosis
      diagnosis. In conclusion, an ultrasound with a high index of clinical suspicion
      is a useful test for the diagnosis of ileocecal tuberculosis. The coned
      contracted cecum with a dilated edematous terminal ileum are important diagnostic
      signs.

PMID- 9261594
TI  - Massive lower gastrointestinal hemorrhage in patients with portal hypertensive
      enteropathy: a report of two cases.
AB  - Mucosal and vascular changes in the lower gastrointestinal tract occur commonly
      in patients with portal hypertension. Portal enteropathy, however, is usually
      asymptomatic, though occasionally clinically significant for chronic
      gastrointestinal bleeding. Massive hemorrhage has only rarely been described and
      its management is controversial. Even though more effective non-operative
      treatments are now available, an emergency porta-systemic shunt procedure remains
      an important option for selected patients. We report on two cases of massive
      lower gastrointestinal bleeding from portal hypertensive enteropathy secondary to
      post-viral cirrhosis.

PMID- 9261596
TI  - Bezoar manifested with digestive and biliary obstruction.
AB  - BACKGROUND/AIMS: Gastrointestinal obstructions caused by bezoars are uncommon but
      are encountered with increasing frequency in general surgery. METHODOLOGY: We
      made a retrospective review of 30 cases treated in the National Cheng Kung
      University hospital between July 1988 and December 1994. RESULTS: Fourteen
      patients had either prior gastric surgery (9) or peptic ulcer disease (5) and
      were categorized as group I. The remaining 16 patients without above conditions
      were categorized as group II; and seven of them had history of ingestion of Pho
      Pu Zi (Cordia dichotoma Frost. f.), three had food bolus ingestion, two had
      diverticulum, two had adhesion and the remaining two had no significant features.
      Two patients, who received endoscopic removal of gastric bezoar and subsequently
      developed bowel obstruction, needed operation. Sixteen of 30 who underwent
      operation within 24 hours after arrival, recuperated uneventfully and most were
      discharged within a week. Eleven patients who received operation after 24 hours
      resulted in prolonged hospitalization in 9 and death in two. Re-operation was
      performed in one case for the recurrence of obstruction by the residual bezoar.
      CONCLUSION: Dietary factors (Pho Pu Zi or bolus ingestion), and gastrointestinal
      (GI) anatomical lesion (diverticulum or adhesion) are the profound etiologies for
      formation of bezoars in cases without previous gastric surgery. On the other
      hand, gastric factors (previous ulcer surgery or peptic ulcer) play a major role
      even after ingestion of nonspecific high fiber diet. Early diagnosis, surgical
      intervention without delay and thorough exploration of the entire GI tract are
      essential for good postoperative results.

PMID- 9261597
TI  - Effect of collateral circulation on healing of small intestinal anastomosis in
      rabbits.
AB  - BACKGROUND/AIMS: In patients who have acute superior mesenteric artery occlusion
      and clearly gangrenous intestines, resection and anastomosis have been advised as
      the only surgical procedure. Distal and proximal bowel segments adjacent to this
      necrotic part have collateral blood supply although they have normal macroscopic
      appearance. After resection of necrotic segment, there will be a low flow at the
      anastomosis due to collateral circulation and the healing may therefore be
      impaired. METHODOLOGY: This situation was investigated in rabbits creating
      unilateral collateral circulation at the small bowel anastomosis. Bursting
      pressure, tissue hydroxyproline concentration and bursting sites were determined
      on days 4, 8, and 12. Findings were compared with the those of normal
      anastomosis. RESULTS: There was significantly decreased mean bursting
      pressure(106 +/- 40.3 mmHg) in unilateral collateral circulation group as
      compared with the that of control group (158 +/- 26.6 mmHg) on day 8 (p < 0.05).
      On the same day mean hydroxyproline concentration of this group was also
      lower(7.06 +/- 0.5 mg/g tissue) than the value of control group(7.69 +/- 0.4 mg/g
      tissue), with the statistical significance on the border line(p = 0.05). The low
      values of these two parameters reached normal levels on day 12. Bursting sites
      were mostly on the anastomotic line in unilateral collateral circulation group,
      while they were mostly on the bowel wall in the control group on day 8.
      CONCLUSION: These findings suggest an insufficient healing process in the bowel
      anastomosis with unilateral collateral circulation on day 8 in rabbits.

PMID- 9261598
TI  - Morphometric study of the small bowel mucosa in infants with diarrhea due to
      enteropathogenic Escherichia coli strains.
AB  - BACKGROUND/AIMS: Enteropathogenic Escherichia coli (EPEC) strains are the most
      important cause of gastroenteritis in infants under 1 year of age and may induce
      several patterns of villous atrophy in the intestinal mucosa. However, the
      interpretation of these abnormalities has usually been based on semiquantitative
      criteria, giving rise to considerably subjective results. We utilized the linear
      morphometry to analyze the morphological lesions of the small bowel mucosa
      induced by EPEC strains in infants with persistent diarrhea in comparison with
      those seen in infants with asymptomatic environmental enteropathy (AEE) and
      controls. METHODOLOGY: Fifty nine specimens of small bowel mucosa were
      comparatively studied and divided in the following groups: 1. Group I: Thirty
      infants with persistent diarrhea due to EPEC strains, mean age 6.4 months; 2.
      Group II: Sixteen infants with AEE, mean age 6.5 months with no enteropathogenic
      bacteria in stools; 3. Group III: Thirteen children with short stature and no
      gastrointestinal complaints, mean age 15 months. Morphometric analysis of the
      small bowel mucosa was performed by using a x10 objective to a Zeiss light
      microscope, to which a measuring Zeiss ocular, t8x was adapted. The following
      measurements were carried out: Total mucosal thickness (TMT); Villous height
      (VH); Crypt length (CL); Intraepithelial lymphocyte (IEL) count. RESULTS: Except
      for the IEL, there was a significant difference in all the parameters analyzed
      among the evaluated groups. Group I revealed the lowest values for total mucosal
      thickness, villous height, and the ratio villous height/crypt length in
      comparison with the two other groups. On the other hand, the crypt length
      measurements for Group II were larger than those for Groups I and III. The
      measurements of villous height and the ratio villous height/crypt length for
      Group III turned out to be greater than those for Group II. CONCLUSIONS: The
      utilization of an accurate technique in the morphological study of the small
      bowel mucosa allowed us to detect severe abnormalities not only in infants with
      EPEC infection, but also in those counterparts who live in contaminated
      environments, and can therefore potentially acquire this type of intestinal
      infection.

PMID- 9261599
TI  - Factors influencing incidence and extension of metachronous liver metastases of
      colorectal adenocarcinoma. A multivariate analysis.
AB  - BACKGROUND/AIM: Three hundred and eighty-seven patients surgically treated for
      colorectal adenocarcinoma were assessed by a multivariate analysis and the
      factors influencing incidence and extension of metachronous liver metastases
      studied. METHODOLOGY: A series of 387 patients which had been surgically treated
      for colorectal adenocarcinoma between January 1980 to December 1990 and followed
      up over a minimum of a 5-year period was retrospectively studied. RESULTS: The
      most reliable prognostic markers are represented by tumor site (p < 0.05) and,
      more specifically, by wall infiltration (p < 0.01) and metastatic lymph-nodes (p
      < 0.05). The only independent variable with a significant impact on stage of
      metachronous liver metastases was proved to be the depth of wall infiltration (p
      < 0.05). CONCLUSION: This study confirms the reliability of some indicators of
      primary tumor in influencing incidence, but not extension, of metachronous liver
      metastases and this is the main problem when it comes to using prognostic factors
      in order to modulate the intervals of postoperative follow-up according to risk
      category.

PMID- 9261600
TI  - Differences between colorectal adenomas removed endoscopically and surgically.
AB  - BACKGROUND/AIMS: To date, risk factors for severe dysplasia in colorectal
      adenomas have been studied mainly in endoscopically removed material. The aim of
      this study was to determine whether there are any differences between adenomas
      removed endoscopically and surgically in terms of patient and polyp
      characteristics. METHODOLOGY: Between 1978 and 1993, 5092 consecutive patients
      with 9874 colorectal adenomas attending the Medical and Surgical Departments of
      the University of Erlangen were prospectively documented in the Erlangen Registry
      of Colorectal Polyps, and statistically examined using regression analysis.
      RESULTS: 5995 adenomas were removed endoscopically from 3343 patients. 3879
      adenomas were surgically resected in 1749 patients. 313 (9.4%) of the former, and
      218 (12.5%) of the latter, patients harboured adenomas with severe dysplasia. The
      size of the adenoma and the tubulovillous or villous structure were the leading
      risk factors, both in endoscopically and surgically removed adenomas. Adenomas
      located in the right colon were at a lower risk in both endoscopic and surgical
      specimens. The risk factors in endoscopically removed adenomas can be described
      by a model of independent variables. However, the risk of severe dysplasia in
      surgically resected adenomas needs to be described in an interactive model.
      Villous structure act as a confounder which modifies the risk profile by
      increasing the risk associated with multiplicity and right-sided location.
      CONCLUSIONS: The risk of severe dysplasia in colorectal adenomas needs to be
      described in different models, depending on the method of adenoma removal-either
      endoscopic or surgical. A global model describing the colorectal dysplasia
      carcinoma sequence will depend on the composition of the endoscopically or
      surgically removed adenomas and will be a more complex model than the clear and
      simple description applicable to purely endoscopic studies.

PMID- 9261601
TI  - Liver metastasis rare in colorectal cancer patients with fatty liver.
AB  - BACKGROUND/AIMS: As no reports in terms of the relationship between fatty liver
      and liver metastasis of colorectal cancer clinicopathological analysis of
      colorectal cancer patients with fatty were found a liver was carried out.
      PATIENTS AND METHODS: Among 839 patients with single colorectal carcinoma who
      underwent operations at our department between 1985 and 1994, 121 patients were
      designated as fatty liver using ultrasonography (FL group). The remaining 718 non
      fatty liver patients with colorectal cancer (NFL group) were compared to the FL
      group regarding clinicopathological aspects. RESULTS: (1) There were only two
      patients who had liver metastasis in the FL group (1.7%), while the NFL group
      included 115 patients with liver metastasis (16.0%) (p < 0.01). (2) The five-year
      survival rate of the FL group was 95.7%, which was significantly higher than that
      in the NFL group (9.8%) (p < 0.001). (3) In the multivariate analysis, the fatty
      liver was identified as an independent prognostic factor. CONCLUSIONS: The FL
      group had a much better prognosis compared to the NFL group. Especially, liver
      metastasis was extremely rare in the FL group. We believe that these results will
      lead to the clarification of the liver metastasis mechanism.

PMID- 9261602
TI  - Influence of alcohol on gastrointestinal motility: lactulose breath hydrogen
      testing in orocecal transit time in chronic alcoholics, social drinkers and
      teetotaler subjects.
AB  - BACKGROUND/AIMS: The gastrointestinal tract is directly affected by the ingestion
      of alcohol. While the effect of acute ingestion of alcohol on the motility of the
      small intestine is well known, the influence of chronic intake of moderate
      amounts of alcohol and chronic alcoholism on gastrointestinal motility remains
      poorly understood. The aim of this study was to examine the orocecal transit
      (OCt) times in patients with chronic alcoholism and in "social drinkers" and
      compare them with a group of healthy teetotaler subjects, to assess the effects
      of chronic aleohol consumption on gastrointestinal transit through the
      application of a non-invasive technique: the hydrogen breath test. METHODOLOGY:
      Thirty-one alcoholics were enrolled in the study. The control groups consisted of
      31 healthy social drinkers and 24 healthy teetotaler subjects. OCt time was
      assessed using the hydrogen breath test after the administration of 10 g of
      lactulose. RESULTS: The OCt time in patients with alcoholism was significantly
      delayed as compared with the social drinkers (p < 0.001) and healthy teetotaler
      subjects (p < 0.001); the OCt time in social drinkers was significantly longer
      than in healthy teetotaler subjects (p < 0.05). In the alcoholic group, there was
      no significant correlation between the OCt time and daily alcohol intake or years
      of alcohol addiction. CONCLUSION: Our results show a significant prolongation of
      the OCt time, both in patients with alcoholism and in social drinkers, as
      compared to teetotaler subjects. Our findings of an increased OCt time related to
      the consumption of alcohol could support the hypothesis of the toxic effect of
      ethanol on smooth muscle contractile proteins of the small intestine and on vagal
      function.

PMID- 9261603
TI  - Gastrin levels in patients with colorectal cancer.
AB  - BACKGROUND/AIMS: In view of previous studies showing gastrin's trophic effects on
      tumor growth, the authors decided to investigate the relationship between fasting
      serum gastrin levels and the presence of colorectal carcinoma. METHODOLOGY: Fifty
      eight patients were studied: 19 controls who were blood bank donors, 19 patients
      with colorectal neoplasms, Dukes' Stage B or C, and 20 patients with advanced
      colorectal neoplasms (Dukes' Stage D). Pre-surgical and post-surgical serum
      gastrin levels were compared in patients with colorectal neoplasms (Dukes' Stage
      B or C). RESULTS: The mean serum gastrin level was 32.3 pg/ml for the control
      group, 52.1 pg/ml for the second group and 49.5 pg/ml for the third group. There
      were no differences between patients before and after surgery. CONCLUSION: These
      results do not confirm the hypothesis that gastrin levels are elevated in
      colorectal cancer patients.

PMID- 9261604
TI  - Enterocutaneous fistulas: an unusual solution.
AB  - Enterocutaneous fistulas are not a minor problem in gastrointestinal tract
      surgery. Significant reduction of mortality and morbidity has been attained but
      they still remain high. The authors report three clinical cases in which they
      sealed and treated enterocutaneous, chronic, iatrogenic fistulas by injecting
      biological glue (N-Butil 2-Cyanoacrylate-Histoacryl) into the internal opening
      and fistulous tract. We believe that the technic we propose here, in the proper
      setting, may be an important contribution to the management of iatrogenic
      (postoperative) enterocutaneous fistulas.

PMID- 9261605
TI  - Necrotizing granulomatous vasculitis of transverse colon and gallbladder.
AB  - A 52-year-old man suffering neither from allergies or asthma, with necrotizing
      granulomatous vasculitis (allergic granulomatosis) of the transverse colon and
      gallbladder is presented. During an emergency laparotomy, segmental necrosis of
      the mesenteric side of the mid-transverse colon, and a bulky enlarged gallbladder
      were found. The affected colon was resected and cholecystectomy was performed.
      Histological findings included necrotizing granulomatous vasculitis of the small-
      and medium-sized muscular arteries and adjacent veins with tissue infiltration by
      eosinophils and extravascular eosinophilic granulomas. These histological
      features were compatible with allergic granulomatous angitis described by Churg
      and Strauss (CSS). The patient had neither asthma nor involvement of two or more
      extra-pulmonary organs which is a key clinical criteria of CSS and fulfilled the
      criteria of eosinophilia alone. Although pulmonary vasculitis was not confirmed
      in this patient, the histological diagnosis of this patient was definitive CSS.
      Localised PAN with allergic granulomatosis or an isolated or limited form of CSS
      based on these clinical features may be an alternative entity.

PMID- 9261606
TI  - A new approach in the management of Crohn's disease: observations in 20
      consecutive cases.
AB  - Although the "modern history" of Crohn's disease dates back to 1932, the etiology
      is still nebulous, the medical treatment inefficient and resective surgery
      results in a high recurrence rate. Twenty consecutive patients with terminal
      ileitis underwent ileo-cecal resection and mesenteric-epiploonplasty to enhance
      collaterals and lymphatic drainage. This approach was advised by experimental
      observations (the ligation of colonic lymphatic ducts in rabbits), by the
      intraoperative use of optics to better appreciate the details of the diseased
      bowel before and after injecting dye and by the angiographic results in one
      patient. In rabbit experiments, the obliteration of lymphatic drainage led to
      Crohn's disease-like macroscopic and microscopic patterns, while diffusion of the
      dye injected in the diseased segment showed altered lymph flow. The angiographic
      study in one patient confirmed the presence of vascular anomalies. Direct
      observation through optics revealed large vessels in the serosa with milky
      contents and the oozing of sticky exudate. In the 8 patients who underwent this
      procedure over 5 years ago, there were no recurrences. We strongly believe in the
      vasculo-lymphatic etiology of Crohn's disease and in mesentery-epiploonplasty as
      the only actual indirect approach to resolve hemolymphatic obstructions.

PMID- 9261607
TI  - Primary biliary cirrhosis: an electronic diagnostic tool trial based on symptoms,
      (past) history and signs only, using the European database euricterus. The
      Euricterus PMG.
AB  - BACKGROUND/AIMS: Primary Biliary Cirrhosis (PBC) is a relatively rare chronic
      progressive disease in which a working diagnosis of PBC easily leads to a final
      diagnosis by testing for anti-mitochondrial antibodies. Liver transplantation is
      the only effective treatment. The aim of this study was to test an electronic
      diagnostic tool (tool) for it's ability to include PBC in the working
      differential diagnosis. METHODOLOGY: In the European Union Euricterus project a
      large number of (sub)icteric patients in 17 discrete disease categories, PBC
      being one of them, were gathered prospectively. A tool was developed-using Bayes
      (B) and Trial Algorithm (TA) pattern-recognition and based on items related to
      the history, symptoms and signs of all Euricterus patients. We have tested the
      diagnostic tool on 143 PBC Euricterus patients. RESULTS: PBC was mentioned by the
      tool in 86% (B) and 91% (TA) of the 143 patients. These figures were higher for
      patients under 60 and (TA only) females. Females under 60 (n = 89) scored 92% B
      and 96% TA. A sole diagnosis of PBC was made in 31% (B) and 66% (TA). In the
      other patients with a PBC probability, 7 other (first) diagnoses were presented
      by the tool of which non-alcoholic active liver disease and pancreatic or biliary
      carcinoma were the leaders. These 7 diseases appeared evenly distributed along
      the percentual probabilities of PBC given by the tool (B) and also along Pugh and
      Mayo scores (B and TA). PBC was mentioned by the tool in all patients with a Pugh
      score 10 or higher (advanced disease, class C). In the patients in whom the tool
      did not mention PBC, the primary diagnoses came from 9 other disease categories.
      CONCLUSION: This electronic tool has been able to identify PBC as one of the
      differential diagnostic modalities in the large majority of a present population
      of PBC patients.

PMID- 9261608
TI  - Modified serum pancreolauryl test in chronic pancreatitis: evaluation in
      comparison to endoscopic retrograde pancreatography.
AB  - BACKGROUND/AIMS: The aim of this study was to assess the applicability and
      accuracy of the modified serum pancreolauryl test (sPLT) in patients with chronic
      pancreatitis (cP). METHODOLOGY: We compared the results of a modified serum
      pancreolauryl test to morphological changes as detected by endoscopic retrograde
      pancreatography (ERP) in 60 patients with a history suggesting chronic
      pancreatitis were compared. Serum fluorescein was measured 30, 60, 120, 150, 180
      and 240 minutes after the ingestion of fluoresceindilaureat, a standardized
      breakfast, and i.v. administration of secretin (1 U/kg) and metoclopramide (10
      mg). Furthermore, the results of sPLT and ERP were compared to the findings on
      abdominal ultrasonography. RESULTS: Forty of 60 patients suffered from cP
      according to ERP criteria. With a fluorescein cut-off point of 4.5 micrograms/ml,
      sPLT reached a sensitivity of 68% and a specificity of 50%. According to the ROC
      curve, the optimal cut-off point was at a fluorescein level of 4.1 micrograms/ml;
      however, predictive accuracy was only slightly improved at this point. In the
      subgroup of patients with advanced pancreatic duct changes (n = 23), however,
      sPLT reached a sensitivity of 87% with 16 patients showing a peak fluorescein
      concentration below 2.5 micrograms/ml. CONCLUSION: Like other indirect pancreatic
      function tests, modified sPLT provides good recognition of patients with advanced
      cP but poor identification of patients with mild or moderate cP, leading to an
      unsatisfying overall performance of the test.

PMID- 9261609
TI  - Preoperative differential diagnosis of benign and malignant pancreatic lesions-
      the value of pancreatic secretory trypsin inhibitor, procarboxypeptidase B, CA19
      9 and CEA.
AB  - BACKGROUND/AIMS: Pancreatic secretory trypsin inhibitor (PSTI).
      Procarboxypeptidase B (PCPB or Human pancreas-specific protein HPASP), CA19-9 and
      CEA were evaluated for their performance in preoperative differential diagnosis
      of benign and malignant pancreatic lesions. METHODOLOGY: Our prospective study
      included 92 patients with pancreatic lesions diagnosed by imaging techniques. In
      45 of them (group I), the lesions turned out to be malignant tumors (35
      pancreatic cancer, 10 other carcinoma of the pancreatic region); 47 patients
      (group II) had benign lesions (38 inflammatory disease of the pancreas, 9 other
      benign lesions). RESULTS: Statistical analysis showed significant differences
      between these two groups for PSTI, PCPB and CA19-9, but not for CEA. When only
      pancreatitis versus pancreatic cancer was analyzed, differences were more
      significant for PSTI and PCPB, but less significant for CA19-9. Because of a
      strong trend toward false positive values in patients with pancreatic
      inflammation, the specificity of CA19-9 in our selected patient group was only
      67%, but in combination with normal PSTI (< 13.5 ng/ml), it reached 96%.
      CONCLUSION: In our study, PSTI and PCPB were useful markers for pancreatitis.
      PSTI also showed good correlation with the severity of the inflammation and
      provided additional preoperative information, in combination with CA19-9.

PMID- 9261610
TI  - Papillary cystic neoplasm of the pancreas: a description of two clinical cases.
AB  - Papillary-cystic neoplasm of the pancreas is a rare neoplasm principally
      effecting women in the 2nd and 3rd decades of life. It is considered a low grade
      malignancy due to it's favourable prognosis and the rarity of metastatic
      diffusion. Pre-operative diagnosis is rare due to the similarity with other
      cystic pancreatic lesions. It is for this reason that definitive diagnosis is
      made at histologic examination of the surgical specimen and total surgical
      excision represents the therapy of choice. The authors herein describe 2 cases of
      papillary-cystic neoplasm of the pancreas, thus bringing the total number of
      cases reported in the world literature to 294.

PMID- 9261611
TI  - Surgical treatment of gastric cancer detected by mass screening.
AB  - BACKGROUND/AIMS: It is crucial to improve the postoperative prognosis of patients
      with gastric cancer in geographic regions where the incidence of gastric cancer
      is high. This study compared the efficacy of surgical treatment in patients with
      gastric cancer detected by a mass screening survey with that of patients
      diagnosed in accordance with standard medical practice. METHODOLOGY: The subjects
      included 189 patients with gastric cancer detected by a mass screening survey
      (screening group) who underwent surgical treatment from 1988 to 1995, and 517
      patients who underwent a standard medical work-up (non-screening group). RESULTS:
      The incidence of early gastric cancer, curative resectability rate, and 5-year
      survival rates between the screening and non-screening groups were 73.0% versus
      48.4% (p < 0.01), 90.5% versus 66.7% (p < 0.01), and 86.2% versus 61.0% (p <
      0.01), respectively. CONCLUSIONS: Surgical treatment for patients with gastric
      cancer identified by mass screening is effective in saving lives and reduces the
      mortality from gastric cancer in the target population of mass screening.
      However, a further prospective randomized controlled study of this screening
      method will be necessary in the future.

PMID- 9261612
TI  - Histological evaluation of lymph node metastasis on serial sectioning in gastric
      cancer with radical lymphadenectomy.
AB  - BACKGROUND/AIMS: Lymph node metastasis is one of the most important prognostic
      factors in gastric cancer patients. To evaluate the real extent of lymph node
      metastasis from gastric cancer, histological examination by serial sectioning was
      performed. METHODOLOGY: Histological examination of serial sections of lymph
      nodes was performed in 111 gastric cancer patients who underwent radical
      gastrectomy, to evaluate methods of examining lymph node metastasis. A total of
      58430 cross-sections of 3449 lymph nodes were examined. The extent of lymph node
      metastasis was evaluated by the routine one-section method, the 3-section method
      and the serial sectioning method for lymph node examination. RESULTS: The
      frequency of lymph node metastasis was 81.1% (90/111) and metastatic foci were
      detected in 23.0% of all lymph nodes by serial sectioning. Serial sectioning of
      distant lymph nodes showed metastasis in 23.8% by the 1 section method, and 8.4%
      by the 3-section method. Micrometastasis was detected in 10.5% of metastatic
      lymph nodes, and distant lymph nodes had a higher rate of micrometastasis.
      CONCLUSION: Serial sectioning resulted in more accurate evaluation of the extent
      of lymph node metastasis, and it was also shown that distant lymph nodes had a
      higher rate of micrometastasis.

PMID- 9261613
TI  - Quality-of-life after curative surgery for gastric cancer: a comparison between
      total gastrectomy and subtotal gastric resection.
AB  - BACKGROUND/AIMS: Quality-of-Life has become an increasingly important factor for
      long term survivors after surgery for gastric cancer. Quality-of Life also
      includes social and psychological aspects. Many gastric carcinomas are located in
      the distal two thirds of the stomach. In these cases, a subtotal gastric
      resection may be adequate if a proximal safety margin of 5 cm in intestinal type
      tumors according to Lauren and 10 cm in diffuse type cancers respectively can be
      achieved. On the other hand total gastrectomy "de principe" has been advocated
      for all gastric malignancies because of high local recurrence rates after
      subtotal resection. The aim of the present study was to assess the Quality-of
      Life in long term survivors after resection for gastric cancer comparing subtotal
      gastric resection with total gastrectomy. METHODOLOGY: One hundred ninety-five
      patients were examined with the Gastrointestinal Quality-of-Life-Index (GLQI).
      Hard clinical data such as postoperative weight loss, frequency of daily meals
      and bowel emptying were evaluated. One hundred five patients were submitted for
      total gastrectomy and in 90 patients a subtotal gastric resection was performed.
      None of the patients had clinical, radiological or endoscopic evidence of
      recurrence. RESULTS: After subtotal gastric resection, patients achieved
      statistically significant better scores concerning disease/therapy-related
      symptoms, physical functions resulting in a better overall score (p < 0.02).
      Following subtotal resection, patients had a significantly lower weight loss
      compared to patients after total gastrectomy (p < 0.02), a smaller number of
      daily meals (p < 0.001) and a lower frequency of bowel emptying/day (p = 0.031).
      There was no statistically significant difference in emotional status or social
      activities showing a similar acceptance of disease and therapy in both groups.
      CONCLUSIONS: In those cases where an adequate proximal safety margin can be
      achieved by a subtotal gastric resection, this procedure is preferable to a total
      gastrectomy. However preservation of the gastric stump should never be allowed to
      compromise oncological radicality.

PMID- 9261614
TI  - Serum pepsinogen I and gastrin in peptic ulcer patients using nonsteroidal anti
      inflammatory drugs.
AB  - BACKGROUND/AIMS: The inhibition of prostaglandin synthesis induced by
      nonsteroidal anti-inflammatory drugs (NSAIDs) have very complex effects on the
      gastric mucosa. They, for instance, inhibit mucosal cell proliferation in gastric
      ulcer patients. The aim of this study was to investigate whether these effects
      manifest as changes in pepsinogen I and gastrin concentrations. METHODOLOGY:
      Fasting serum pepsinogen I and gastrin samples were collected from 53 consecutive
      Helicobacter pylori (HP) positive peptic ulcer patients. Ulcer was diagnosed by
      endoscopy. The presence of HP was determined from the histological specimen taken
      from the antral mucosa. Histological changes in the gastric mucosa were evaluated
      according to the Sydney system. A structured personal interview was carried out
      with all patients at endoscopy, including detailed questions on the daily use of
      NSAIDs. Patients were divided into two groups according to their use of NSAIDs.
      RESULTS: The age-adjusted mean pepsinogen I concentration was significantly lower
      in patients who used NSAIDs compared to those who did not (91 vs 127 ng/l, p =
      0.0035). There was no difference in the mean gastrin concentration between these
      two groups (91 vs 86 micrograms/l, p = 0.74). CONCLUSIONS: Serum pepsinogen I
      concentration was lower in HP positive peptic ulcer patients who used NSAIDs
      compared to those who did not.

PMID- 9261615
TI  - Assessing the permeability of the gastrointestinal mucosa after oral
      administration of phenolsulfonphthalein.
AB  - BACKGROUND/AIMS: In this study, the oral phenolsufonphthalein (PSP) absorption
      test as a simple and non-invasive method for the assessment of either the extent
      of the permeability of or damage to the gastrointestinal mucosa was evaluated.
      METHODOLOGY: The permeability of the gastrointestinal mucosa of patients with
      liver cirrhosis and those who underwent gastrointestinal surgery was assessed by
      the oral administration of 30 mg of PSP and the measurement of its urinary
      recovery rate. RESULTS: The urinary PSP excretion in patients with liver
      cirrhosis (n = 8; 28.8 +/- 6.0%) was significantly higher than that of patients
      who underwent vascular surgery (n = 8; 10.0 +/- 1.7%) (p < 0.01), which thus
      suggested an increased permeability of the gastrointestinal mucosa in patients
      with liver cirrhosis. The urinary PSP excretion rate in patients who underwent a
      total gastrectomy with Roux-en-Y reconstruction (n = 5) was 17.3 +/- 1.7% which
      was significantly higher than that observed in the control (p < 0.05), while the
      same rates in patients who underwent a partial gastrectomy (n = 10) or colectomy
      (n = 10) were 10.2 +/- 1.8% or 10.6 +/- 0.7%, respectively, which suggested that
      the intestinal mucosa is damaged by a total resection of the stomach.
      CONCLUSIONS: The oral PSP absorption test, which is non-invasive, simple and
      inexpensive, is thus considered to be useful for assessing the degree of damage
      to or the permeability of the gastrointestinal mucosa under various conditions.

PMID- 9261616
TI  - Massive extra-enteric gastrointestinal hemorrhage secondary to splanchnic artery
      aneurysms.
AB  - BACKGROUND/AIMS: Gastrointestinal hemorrhages of obscure origin are often
      difficult to diagnose and manage. Of these, splanchnic artery aneurysms have
      emerged as an important disorder because of the increasing prevalence and
      formidable mortality rate associated with their rupture. We herein evaluated
      extra-enteric gastrointestinal bleeding related to these ruptured aneurysms.
      METHODOLOGY: The medical records of 17 patients with splanchnic artery aneurysms
      known to be exclusively manifested as gastrointestinal bleeding were reviewed.
      The pathogenesis, clinical picture, diagnostic tests, management, complications,
      and outcomes were compiled and analyzed. RESULTS: Of the seventeen patients, 12
      patients had true aneurysms; 5 patients had false aneurysms. Pancreatitis,
      trauma, iatrogenic hepatobiliary injury, and atherosclerosis were the four major
      etiologies. The sensitivity rates measured by endoscopy, ultrasonography,
      computed tomography and visceral angiography were 20%, 50%, 67%, and 100%,
      respectively. An exact diagnosis was attained in 94% of the patients at the time
      of management. Transcatheter embolization was employed in 7 patients, complicated
      with hepatic and splenic infarcts, and pyogenic liver abscesses in 2 instances.
      Two patients had recurrent bleeding aneurysms post embolotherapy. Ten patients
      underwent surgical intervention which resulted in 2 cases of hepatic failure. One
      out of 5 patients with a true aneurysm died, while 4 out of 12 patients with
      false aneurysms eventually died. Overall, the mortality rate was 29%. CONCLUSION:
      Even though the exact diagnosis can be made in most of the patients by modern
      imaging studies, the mortality rate was still formidable, especially in patients
      with false aneurysms, in whom the underlying causal diseases substantially
      influenced the major outcome.

PMID- 9261618
TI  - Clinical and pathologic features of early gastric cancer in elderly patients.
AB  - BACKGROUND/AIMS: The purpose of this study was to review the Clinicopathologic
      features of early gastric cancer in elderly patients. METHODOLOGY: Three hundred
      and seventy-two patients who underwent resection for early gastric cancer were
      divided into groups of patients younger and older than 70 years. The clinical and
      pathologic findings surgical treatment, and perioperative complications in the
      group of elderly patients with early gastric cancer were reviewed and compared to
      those of the younger group. RESULTS: Gastric cancer involving the lower third of
      the stomach, as well as histopathologically well-differentiated carcinomas, were
      significantly more prevalent in the older group. Pre-operatively, the older
      patients had a higher incidence of respiratory dysfunction and hypertension. D1
      lymph node dissections were chosen frequently for older patients. Six older
      patients died within 2 months of hospitalization, while no younger patients died
      within this period. The mortality rate mas 11% in older patients undergoing D2 or
      greater extents of node dissection, although the mortality rate was only 2% in
      older patients undergoing a D1 or less dissection. The 5-year survival rate for
      older patients, including deaths unrelated to cancer, was 71%, which was
      significantly lower than that in the younger group. However, when only mortality
      from gastric cancer was considered, patient survival did not differ according to
      age. CONCLUSION: Given the high mortality in elderly patients unrelated to early
      gastric cancer, we concluded that node dissection should be limited to
      perigastric nodes according to tumor location in such patients.

PMID- 9261617
TI  - Primary adenocarcinoma of the duodenum: treatment and survival in 89 patients.
AB  - BACKGROUND/AIMS: Primary adenocarcinoma of the duodenum is a rare disease and
      diagnosis is always late in being confirmed because of the non-specific symptoms,
      consequently leading to poor prognosis. METHODOLOGY: A retrospective review of 89
      patients with non-ampullary duodenal adenocarcinoma treated in 36 different
      surgical departments in Italy between 1980 and 1994 was performed. The signs and
      symptoms, diagnostic studies conducted, tumor locations, surgical treatment, and
      survival were analyzed. RESULTS: Duodenography and endoscopy were the most
      effective diagnostic tests, showing an accuracy of 81.9% and 88%, respectively.
      The most common tumor site was periampullary, observed in 62.9% of the cases. A
      curative resection was performed in 65 of the 89 patients (73%), a partial
      pancreatoduodenectomy in 37, a segmentary duodenal resection in 15 and a wide
      local excision in 11. The postoperative mortality rate was 10.1% (9 patients),
      and the overall 5-year survival was 25%, which was significantly better after
      resection. The most important prognostic factors were stage and tumor location.
      CONCLUSION: Early diagnosis of primary duodenal adenocarcinoma is the only way to
      improve the results, by providing a higher resectability rate.

PMID- 9261620
TI  - Non-lymphoid cancer after liver transplantation.
AB  - BACKGROUND/AIMS: The increasing length of survival of organ transplant recipients
      necessitates careful attention to the potential neoplastic complications of life
      long immunosuppression, which is required for such patients. Previous studies by
      Penn of patients taking triple drug therapy (Cyclosporin, Azathioprine and
      Prednisone) for immunosuppression, or even of those taking Imuran and
      Cyclophosphamide, have shown a high percentage of tumor development (3117 per
      2915 patients). METHODOLOGY: Three thousand three hundred and ninety-four adult
      patients underwent orthotopic liver transplantation (OLTx) at the University of
      Pittsburgh Medical Center, Transplant Institute prior to December, 1992. Of
      these, 1657 were examined (48.8%). All patients with hepatic or biliary cancer as
      the indication for OLTx were excluded; all other indications were considered. All
      forms of tumor development after OLTx were considered, except for
      lymphoprolipherative disease and hepato-biliary tumors. The immunosuppressive
      regimens were reviewed and patients treated with FK 506 and Cyclosporin A (CSA),
      as well as those switched from CSA to FK 506, were divided into different groups.
      RESULTS: A total of 50 patients with tumors were identified (37 males, 13
      females), ranging between 34 and 69 years of age. Of these patients, 48 are still
      alive. In these patients, 64 tumors, classified according to the TMN
      classification, were discovered: 50 in males and 14 in females. Two metastases
      were found following discovery of the tumor. The tumors identified were as
      follows: basalioma 25%, squamous 20.3%, Bowen 6.2%, warts 3.1%, melanoma 6.2%,
      Kaposi's sarcoma 3.1%, colonic adenocarcinoma 3.1%, colonic polyps 4.6%, rectal
      cancer 1.5%, breast cancer 4.6%, cervical cancer 3.1%, ovarian cancer 3.1%,
      laryngeal cancer 3.1%, prostate cancer 1.5%, lung cancer 3.1%, gastric cancer
      3.1%, and hemangioblastoma 1.5%. CONCLUSIONS: Skin cancer is the most common type
      of tumor discovered after liver transplantation (The transplant does not change
      the occurrence in lung transplants with a positive smoking history). A lower
      incidence of tumors was found after liver transplantation as compared to kidney
      transplantation. A higher incidence of tumors was found with CSA, as opposed to
      FK 506 immunosuppression therapy. None of the patients in this series experienced
      acute graft rejection necessitating re-transplantation. Chronic graft rejection
      was treated either with FK 506 or with OKT3, without an increase in the incidence
      of tumor development.

PMID- 9261619
TI  - Surviving catastrophic gastrointestinal involvement due to Churg-Strauss
      syndrome: report of a case.
AB  - Gastrointestinal (GI) involvement is not rarely encountered in Churg-Strauss
      syndrome (CSS). We describe the case of a young white woman presenting with acute
      acalculous cholecystitis, who subsequently developed, despite prompt
      administration of immunosuppressive therapy, life threatening GI involvement,
      requiring multiple operations. Over a 7-month period the patient eventually
      recovered from her disease. Forty-two months later she is free from symptoms,
      with low daily doses (6 mg) of oral methylprednisolone. Although medical and
      surgical complications of CSS may develop while the patient is undergoing
      therapy, early diagnosis with joint surgical and medical management is essential
      to bring the disease under control.

PMID- 9261621
TI  - Comparison of treatment with two different doses of leukocyte interferon alpha in
      patients with chronic hepatitis C.
AB  - BACKGROUND/AIMS: This study was carried in order to investigate whether human
      leukocyte interferon-alpha administered for 12 months at two different dosages,
      improves long-term responses in chronic hepatitis C and to see whether pre
      treatment gamma-glutamyl transpeptidase values help to predict the clinical
      response to Interferon. METHODOLOGY: Forty-five patients were treated for 12
      months with natural Interferon-alpha: 3 MU (group A: 31 cases); 6 MU (group B: 14
      cases). Biochemical and virological responses were monitored during treatment and
      follow-up. RESULTS: Alanine aminotransferase was normalized in 58.1% (Group A)
      and 54.5% (Group B) of patients by the end of the treatment. Due to side effects
      3 patients had to discontinue treatment. During follow-up, remission was
      maintained in 30.8% and 45.4% of patients respectively (p = 0.046). After 12
      months of therapy, respectively 46.7% and 45.4% of patients with complete
      biochemical response, cleared virus from serum, as did, among long-term
      responders, 3/8 and 3/4 evaluated patients. Independently of dosage, a complete
      response was found more often in patients with normal pre-treatment gamma
      glutamyl transpeptidase than in those with pre-treatment abnormal values.
      CONCLUSIONS: High dosage of IFN alpha was associated with a significantly greater
      rate of sustained biochemical response and with a better chance of viremia
      becoming negative. Pre-treatment gamma-glutamyl transpeptidase was able to
      predict the outcome of the treatment.

PMID- 9261623
TI  - Liver involvement and its course in experimental colitis in rats.
AB  - BACKGROUND/AIM: The aim of the study was to evaluate histological liver lesions
      and to compare these with the results of biochemical parametres. METHODOLOGY: An
      experimental model of chronic ulcerative colitis in rats was utilized. RESULTS:
      Histological studies of the biliary tree showed progressive fibrotic inflammation
      which fulfilled the criteria of early sclerosing cholangitis. The biochemical
      tests of liver function were, however normal in all animals. CONCLUSIONS:
      Sclerosing cholangitis in experimental ulcerative colitis is a progressive
      disease, and normal liver biochemistry does not exclude changes in liver
      histology.

PMID- 9261622
TI  - Hepatic tissue microcirculation, oxygenation and energy charge in ischemia
      reperfusion subjected cirrhotic rat liver.
AB  - BACKGROUND/AIMS: The hemodynamic disturbances in the cirrhotic liver following
      severe variceal bleeding and subsequent restoration by blood transfusion is an
      ischemia/reperfusion injury event which represents the clinical situation of
      liver dysfunction. Therefore, the aim of this study was to evaluate the
      microcirculation, oxygenation and energy charge of the cirrhotic rat liver after
      ischemia/reperfusion. METHODOLOGY: In eight carbon tetrachloride-induced
      cirrhotic rats and an equal number of controls subjected to 30 minutes of
      ischemia and 60 minutes of reperfusion by hepatoduodenal ligament clamping, the
      following parameters were assessed: hepatic microcirculation by laser-Doppler
      fluxmetry, hepatic tissue oxygenation by a Clark-type electrode, hepatic energy
      charge by tissue sampling and adenine-nucleotides determination by means of high
      performance liquid chromatography. RESULTS: At baseline, liver microcirculation
      was found to be significantly decreased in the cirrhotics versus controls groups.
      Ischemia led to a reduction in both groups, while reperfusion improved
      microcirculation, but not to the baseline level. Oxygenation was reduced during
      ischemia and restored after reperfusion in both groups. Hepatic energy charge was
      reduced in the cirrhotics versus controls at baseline, and significantly
      decreased during ischemia in both groups. At reperfusion, a further reduction was
      found in the cirrhotic group, while in the control group it was restored to
      baseline. CONCLUSION: Hepatic microcirculation, oxygenation and energy charge are
      subjected to different degrees of diminution after ischemia/reperfusion in the
      cirrhotic rat liver.

PMID- 9261625
TI  - Serum laminin P1 levels do not reflect critically elevated portal pressure in
      patients with liver cirrhosis.
AB  - BACKGROUND/AIMS: Laminin P1 serum levels run parallel to the accumulation of
      hepatic extracellular matrix in patients with liver cirrhosis. Recent studies
      reported a correlation between laminin P1 and portal pressure, leading to the
      proposal that laminin P1 may be used to identify patients with critically
      elevated portal pressure in liver cirrhosis. So far, most of the data has been
      obtained from patients with alcoholic liver disease. METHODOLOGY: We studied the
      relationship between laminin P1 serum levels and portal hypertension in 34
      patients with liver cirrhosis, mostly of non-alcoholic etiology. Using hepatic
      venous catheterisation the hepatic venous pressure gradient (HVPG), an estimate
      of portal hypertension, was measured. Laminin P1 was compared to the HVPG and the
      size of esophageal varices. RESULTS: Serum laminin P1 was elevated in all
      samples. However, laminin P1 did not significantly correlate with either portal
      hypertension or the size of esophageal varices. Furthermore, laminin P1
      measurement did not identify patients with critically elevated portal pressure
      using a HVPG of either 12 mmHg or 16 mmHg as cut-off points. CONCLUSION: The use
      of laminin P1 serum levels to diagnose critically elevated portal pressure in
      liver cirrhosis cannot be supported for etiologies other than alcoholic liver
      disease.

PMID- 9261624
TI  - The role of HBV DNA and liver histopathology in HBsAg carriers.
AB  - BACKGROUND/AIMS: In this study, we evaluated the association among serum
      transaminase values, seropositivity of HBV DNA and liver histopathology of
      patients with positive HBsAg and HBe antibodies. METHODOLOGY: Thirty-five
      patients were placed in two groups according to their serum transaminase values.
      Patients with normal transaminase values were evaluated in the first group. The
      patients with above normal transaminase values were subjected in the second
      group. RESULTS: In the first group of patients with normal transaminase values,
      biopsy-proven moderate or severe chronic hepatitis was not observed. HBV DNA
      seropositivity was 53.3% in this group. Forty-five percent of the patients with
      above normal transaminase values had moderate chronic hepatitis and
      seropositivity for HBV DNA in this group was 55%. Our results supported the
      association between transaminase values and liver pathology, but no statistically
      significant association was shown between seropositivity of HBV DNA and liver
      pathology. CONCLUSION: There is much to be studied to understand the function of
      HBV DNA in the follow up of HBsAg carriers, and liver biopsy has to be used
      routinely in the follow up of asymptomatic carriers when they happen to have high
      transaminase values.

PMID- 9261626
TI  - Endovascular diagnosis and treatment of profuse esophageal bleeding in patients
      with portal hypertension.
AB  - BACKGROUND/AIMS: In this study the possible choices and the most effective
      tactics of endovascular treatment of bleeding from esophageal varicosities in
      patients with portal hypertension were identified. METHODOLOGY: Results of
      angiographic examination and endovascular interventions in 121 patients with
      portal hypertension complicated by esophageal bleeding were analysed in this
      study. Embolization of esophageal varicosities in the first group of patients
      (N(17) was conducted as emergency intervention within 3-4 hours. Endovascular
      occlusion of bleeding vessels in the second group (N(70) was conducted following
      balloon tamponade of varicosities and drug therapy of homeostasis impairment
      within 3-4 days. The treatment in the third group (N(34) was adjusted by intra
      portal infusion of drugs. RESULTS: Embolization of esophageal varicosities
      without correction of homeostasis impairment due to bleeding had a lethal outcome
      in 52.9% of patients. Three to four days after the interventions had been, 13.5%
      of patients died. Combination of embolization of esophageal and gastric
      varicosities with intra-portal infusion of drugs was accompanied by lethal
      outcome in 8.8% of patients. CONCLUSIONS: Success of endovascular treatment of
      esophageal bleeding in patients with portal hypertension depends on adequate pre
      embolization preparation, selection of tactics, volume and terms of its
      filfilment as well as systematic stage-by-stage corrective endovascular
      interventions in distant terms.

PMID- 9261627
TI  - Solitary necrotic nodule of the liver: diagnosis and treatment.
AB  - In 1983, Shepherd and Lee described the solitary necrotic nodule of the liver, an
      uncommon non-malignant lesion with a characteristic histological appearance. This
      nodule can often be misinterpreted as a necrotic secondary tumour. Limited liver
      resection can make differential diagnosis and cure the lesion.

PMID- 9261628
TI  - A giant hepatic hemangioma with secondary portal hypertension: a case report of
      successful surgical treatment.
AB  - A case of a giant cavernous hemangioma of the liver is presented. Selective
      angiograms revealed secondary portal hypertension, probably caused by a temporal
      obstruction of the extra-hepatic portal vein due to the physical pressure of the
      tumor, and a marked dislocation of the hepatic artery. The patient also had
      consumption coagulopathy. Both the portal obstruction and hematological disorders
      improved after excision of the tumor. Since surgery the patient has been in good
      health with no complaints or recurrence.

PMID- 9261629
TI  - Aureobasidium pneumonia in a post liver transplant recipient: a case report.
AB  - This is the first report of Aureobasidium (A.) pullulans as an opportunistic
      pulmonary infection in a liver transplant recipient. A 46-year-old caucasian man
      had an orthotopic liver transplant in 1988. His liver disease was primary
      sclerosing cholangitis. He required 2 subsequent liver re-transplants for primary
      graft non-function and acute rejection. The patient had been living in the
      California desert for two months prior to admission and presented with ventilator
      dependent acute respiratory failure and hemodialysis-dependent acute renal
      failure. Imaging studies revealed severe bilateral infiltrates. His initial
      bronchoalveolar lavage (BAL) and brushings grew A. pullulans. Pancultures,
      including sputum and throat cultures, were negative for bacterial or other fungal
      organisms. The patient responded to pulmonary support and aggressive systemic
      antifungal agents while being maintained on cyclosporine and prednisone for
      immunosuppression. He was discharged to a skilled nursing facility 37 days after
      hospitalisation. Delay in discharge was primarily due to severe malnutrition and
      renal impairment. Opportunistic fungal infections continue to be a major problem
      in immunosuppressed patients including liver transplant recipients. Here we
      report a pulmonary infection with Coccidioides (C.) immitis and superinfection
      with A. pullulans. Opportunistic infections such as A. pullulans can be treated
      successfully with systemic fluconazole when amphotericin B is not well tolerated.

PMID- 9261630
TI  - Hepatic venous injury; a case report of atriocaval shunt by a centrifugal pump.
AB  - Injury of hepatic vein confluence and retrohepatic vena cava is serious and often
      fatal. We report one such case that was successfully treated by the Biopump
      (Medtronic Bio-Medicus, Inc., Eden Prairie, Minn). A 21-year-old man was admitted
      due to a steering-wheel injury in a motor vehicle accident. CT scan showed
      extravasated contrast material around the right hepatic lobe, and a large low
      density area in the right hepatic lobe adjacent to the inferior vena cava,
      suggesting injury of the hepatic vein confluence or the retrohepatic vena cava.
      The patient underwent surgical treatment. Laceration of the liver was extended to
      the hepatic vein confluence. Right hepatic lobectomy and repair of the middle
      hepatic vein was successfully performed under atriocaval shunting by the Biopump.

PMID- 9261631
TI  - Unresectable pancreatic cancer: is a multi-modality approach a promising
      therapeutical alternative?
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate the combination of
      immunochemotherapy and stop-flow upper abdominal chemotherapy in the prolongation
      of survival in patients with unresectable pancreatic cancer. METHODOLOGY: Thirty
      unresectable pancreatic cancer patients were treated with immuno-chemotherapy in
      combination with stop-flow upper abdominal chemotherapy, in an attempt to improve
      survival time. RESULTS: The results obtained in this study indicate that this
      kind of treatment is feasible, safe and effective for patients suffering from
      Stage III and IV pancreatic duct carcinoma. Twenty per cent of the patients
      within this group were able to undergo radical resection and remain alive and
      free of disease, with a mean survival rate of 16 months. CONCLUSION: The multi
      modality approach used in this study achieved promising results for pancreatic
      cancer patients and is recommended as a promising therapeutic alternative.

PMID- 9261632
TI  - Platelet aggregability and occurrence of restenosis following coronary
      angioplasty.
AB  - Restenosis following percutaneous coronary angioplasty (PTCA) is a complex
      medical problem occurring in nearly a third of the patients undergoing PTCA with
      no single definite predictor demonstrated in an individual patient. Platelets are
      known to play an important role in the pathogenesis of the restenotic process.
      However, no known parameter of platelet function or activity has been studied as
      a risk factor predicting the occurrence of restenosis. We prospectively assessed
      platelet activation in twenty two consecutive patients with stable angina who
      underwent a successful PTCA for single vessel coronary artery disease. Platelet
      activation levels were measured using aggregability curves derived from unclotted
      blood samples on a platelet aggregometer using varying concentrations of
      adenosine di-phosphate (ADP) in the following time sequence: (1) Basal i.e. pre
      PTCA, (2) post-PTCA day 1, (3) post-PTCA day 7, and (4) post-PTCA day 28.
      Occurrence of restenosis was studied using angiographic follow-up in all
      patients. At follow-up, seven of the twenty two patients studied developed
      restenosis. There was no significant difference or any specific trend noted over
      time in the levels of platelet aggregability in the study group as a whole
      (basal: 30.0 +/- 15.4%, post-PTCA day 1: 32.5 +/- 16.1%, post-PTCA day 7: 34.6 +/
      15.4% and post-PTCA day 28: 32.6 +/- 16.1%). However, when the patients were
      subgrouped into those with and without restenosis, the patients with restenosis
      had a significantly higher basal platelet aggregability (38.7 +/- 16.3%) versus
      those who did not develop restenosis (25.0 +/- 12.1%), p = 0.0128. We conclude
      that patients developing restenosis after PTCA have a significantly higher basal
      platelet aggregability and this could be used as a marker for its occurrence in
      an individual patient.

PMID- 9261633
TI  - Spontaneous regression of post-percutaneous transluminal coronary angioplasty
      aneurysm.
AB  - We report a case of a 67-year-old male with spontaneous regression of post
      percutaneous transluminal coronary angioplasty (PTCA) aneurysm. This case
      substantiates the benign prognosis of post-PTCA aneurysms.

PMID- 9261634
TI  - Echocardiographic evaluation of cardiac function in paediatric oncology patients
      treated with or without anthracycline.
AB  - Using Doppler echocardiography, we studied the left ventricular systolic and
      diastolic function in 124 healthy control children (group C), 110 oncology
      patients who had received anthracycline (group A), and 76 oncology patients who
      had received chemotherapy not including anthracycline (group N), at rest and
      after supine bicycle exercise. The mean dosage of anthracycline that group A
      patients received was 219 +/- 95 mg/m2. Impaired systolic function was detected
      in 29% of the patients in group A and 4% in group N. Figures for impaired
      diastolic function for group A and N were 27% and 28% respectively. Abnormal
      diastolic function was detected more frequently in the first two years after
      chemotherapy in both groups. Four parameters measured at rest appeared to be
      specifically abnormal in group A but not in group N. These were ejection
      fraction, fractional shortening, rate-corrected velocity of circumferential fiber
      shortening (VCFC) and left ventricle peak systolic wall stress (LVWS). After
      exercise more parameters were abnormal in group N patients when compared to
      normal children, but abnormalities of VCFC and LVWS remained specific for group
      A. In conclusion, abnormalities of diastolic function were common among
      paediatric oncology patients no matter whether they had received anthracycline
      treatment or not. Abnormalities of systolic function were more specific to
      anthracycline toxicity. VCFC and LVWS were the most sensitive measurements for
      differentiating group N patients from group A patients.

PMID- 9261635
TI  - Rare variants of divided right ventricle with sequestered apical trabecular
      component.
AB  - The right ventricle may be divided into two or more compartments by various
      structures in various ways. Rarely, the apical trabecular component may be
      sequestered from the rest of the right ventricle. We report 4 cases with
      different underlying lesions that share a common pathology of apical
      sequestration of the right ventricle resulting in diverse hemodynamic
      consequences. Case 1 had pulmonary valve stenosis. The apical sequestration of
      the right ventricle resulted in no significant hemodynamic consequence. Case 2
      had multiple defects in the muscular ventricular septum. The volume of left-to
      right shunt seemed to be reduced because of the commitment of some of the defects
      to the sequestered cavity. Case 3 had a large defect in the trabecular septum. As
      the defect involved the whole septum that was related to the sequestered right
      ventricular apex, the left ventricle together with the sequestered right
      ventricle formed a boot-shaped chamber. Hemodynamically, the muscular shelf was
      an interventricular septum. Case 4 had a coronary artery fistula to an isolated
      cavity that occupied the apical region of the right ventricle. The pathology was
      similar to the case that was reported as a five-chambered heart. The abnormal
      cavity was, in fact, the sequestered right ventricular apex.

PMID- 9261636
TI  - Cardiac involvement in childhood polyarteritis nodosa.
AB  - In this report, we evaluated the cardiac findings of 15 children with
      polyarteritis nodosa. The age range of the patients was 4-14 years; with a mean
      of 10 years. All have had systemic involvement of the disease. The most common
      findings in cardiac evaluation were diminished left ventricular systolic
      functions and mild mitral and/or tricuspid valve regurgitation. One patient had
      pericardial thickening with no effusion. One had sinus tachycardia. There were no
      signs of myocardial infarction or ischemia clinically or electro
      cardiographically. In conclusion, we did not find cardiac complications, such as
      pericarditis or myocardial infarction, to be as frequent as in previous reports.
      However, even in asymptomatic patients, systolic dysfunction or valvular
      involvement were common findings in patients with polyarteritis nodosa, which
      were not reported previously. These findings may be due to the histological
      changes of the myocardium or atrioventricular valves. Although these were not
      severe and fatal lesions, long-term follow-up of these patients with
      echocardiography may help to determine the course of cardiac involvement.

PMID- 9261637
TI  - Influence of hemodynamic changes on neuroendocrine response in acute heart
      failure.
AB  - We studied 15 patients with acute deterioration of chronic left ventricular heart
      failure. We compared the influence of reduction of ventricular filling pressures
      with glyceryl trinitrate versus reduction of ventricular filling pressures with
      diuretics on plasma concentration of epinephrine, norepinephrine, aldosterone and
      renin activity. Reduction of ventricular filling pressures with glyceryl
      trinitrate had no influence on plasma concentrations of epinephrine,
      norepinephrine, aldosterone and renin activity. After reduction of ventricular
      filling pressures with diuretics plasma concentrations of epinephrine,
      norepinephrine and aldosterone decreased, while plasma renin activity did not
      change. We conclude that there is a difference in the influence of reduction of
      ventricular filling pressures with glyceryl trinitrate versus reduction of
      ventricular filling pressures with diuretics, on neuroendocrine response in
      patients with acute deterioration of left ventricular heart failure. Thus some of
      the neuroendocrine effects of glyceryl trinitrate are likely to be different from
      those of diuretics, though that they both produce a reduction in left ventricular
      filling pressure.

PMID- 9261639
TI  - Normal angiogram after myocardial infarction in young patients: a prospective
      clinical-angiographic and long-term follow-up study.
AB  - This is an observational study in which we compared the clinical characteristics
      and the long-term course of young patients having acute myocardial infarction and
      angiographically normal coronary arteries and young patients showing significant
      coronary artery disease. In 87 patients aged < or = 40 years who suffered an
      acute myocardial infarction, enrolled in a prospective study over a period of 6.5
      years, coronary anatomy was determined by angiography within a month of
      admission. The risk factors, clinical data, ventricular function and the long
      term outcome were compared between patients with normal angiograms (Group 1, n =
      12) and patients with coronary artery disease (Group 2, n = 75). Patients in
      Group 1 had a lower number of risk factors associated with them (17% vs. 64% with
      > 1 risk factor, P < 0.005), were younger (32 +/- 5 vs. 36 +/- 4, P < 0.01),
      lighter smokers (25% vs. 55% for > or = 2 packs per day, P < 0.05), had less
      frequent hypertension (0 vs. 25%, P < 0.05), hypercholesterolemia (17% vs. 52%, P
      = 0.02) and had a lower mean total cholesterol level (201 +/- 42 vs. 245 +/- 60
      mg/100 ml, P < 0.05) than patients in Group 2. They also had a more common onset
      of their infarction during heavy physical exertion (67% vs. 17%, P < 0.001). A
      history of previous myocardial infarction, infarct location, global left
      ventricular function and regional wall motion were similar in both groups. After
      a mean follow-up period of 41 +/- 23 months, no patient died or had a second
      myocardial infarction in Group 1, and 4 patients had died in Group 2. The
      appearance of angina, less frequent in Group 1 than Group 2, tended to correlate
      with the extension of the coronary artery disease. We concluded that young
      patients with myocardial infarction have good prognosis irrespective of the
      coronary anatomy, although patients with normal coronary angiograms had less risk
      factors and less frequent new ischaemic events.

PMID- 9261638
TI  - Abnormalities of cardiocytes in regions bordering fibrous scars of dogs with
      heart failure.
AB  - Progressive deterioration of left ventricular function is a characteristic
      feature of the heart failure state and is often speculated to result from ongoing
      loss of viable myocytes. We previously showed that in dogs with chronic heart
      failure, cardiocyte death through apoptosis occurs in the border region of
      fibrous scars (old infarcts). In the present study we examined the structural
      integrity of cardiocytes in regions bordering fibrous scars using transmission
      electron microscopy. Morphometric studies were performed using left ventricular
      tissue obtained from ten dogs with chronic heart failure produced by
      intracoronary microembolizations. Mitochondrial number increased significantly
      with proximity to the scar, while mitochondrial size decreased leading to a
      gradual decrease in mitochondrial volume fraction. Severe injury to mitochondria
      was present in only 5% of organelles in myocytes far from the scar but increased
      markedly to 28-41% in myocytes adjacent to or incorporated within the scar.
      Similarly, severe myofibrillar abnormalities were present in only 3% of myocytes
      that were far from the scar but increased significantly to 12-73% in myocytes
      adjacent to or incorporated within the scar. These results indicate that in dogs
      with chronic heart failure, constituent myocytes of left ventricular regions
      bordering fibrous scars manifest heterogeneity in the extent of degeneration. The
      extent of degeneration is greatest in myocytes closest to the scar and least in
      myocytes far from the scar. We postulate that this wavefront of myocyte
      degeneration is a dynamic process that may lead to progressive expansion of the
      scar through loss of viable myocytes and ultimately may contribute, in part, to
      the progressive left ventricular dysfunction that characterizes the heart failure
      state.

PMID- 9261640
TI  - Influence of amiodarone on QT dispersion in patients with life-threatening
      ventricular arrhythmias and clinical outcome.
AB  - Increased QT dispersion, defined as the difference between the maximum and
      minimum QT interval on the standard 12-lead electrocardiogram is assumed to
      reflect regional inhomogeneity of ventricular repolarization and has been shown
      to be associated with an increased risk of arrhythmic events. The purpose of the
      present study is to examine the influence of amiodarone on QT dispersion in
      patients with life-threatening ventricular arrhythmias and to evaluate the
      predictive value of QT dispersion after amiodarone therapy for further arrhythmic
      events. ECG's were obtained in 47 patients 1-2 days before and 6-8 weeks after
      amiodarone was started. All patients had coronary artery disease with a mean EF
      of 34 +/- 14%. The QT interval was measured in each lead of a digitized ECG
      displayed on a high resolution monitor (250 mm s-1). Amiodarone therapy resulted
      in a significant increase in the maximal QTc interval (476 +/- 44 to 505 +/- 44
      ms, p < 0.001). However, measurement of QT dispersion (70 +/- 34 vs 73 +/- 29 ms)
      and Qtc dispersion (78 +/- 37 vs 77 +/- 31 ms) revealed no significant difference
      before and after amiodarone. During a one year follow-up period 26 patients were
      free of arrhythmic events and 7 patients developed further arrhythmic events. The
      remaining 14 patients were excluded from the one year follow-up analysis because
      of drug discontinuation (n = 8), death due to heart failure (n = 1), medical
      intervention (n = 3) and incomplete follow-up (n = 2). No measure of QT
      dispersion was predictive of recurrent arrhythmic events during treatment with
      amiodarone. CONCLUSION: Treatment with amiodarone results in significant QT
      prolongation without altering QT dispersion. Measurements of QT dispersion were
      not predictive of amiodarone efficacy in this patient population.

PMID- 9261641
TI  - Plasma homocysteine and the extent of atherosclerosis in patients with coronary
      artery disease.
AB  - Homocysteine is a graded risk factor for the incidence of stroke and for the
      degree of carotid atherosclerosis. Homocysteine is also a graded risk factor for
      the incidence of myocardial infarction but we do not know its precise relations
      to the severity of atherosclerosis in coronary patients. Seventy five symptomatic
      coronary patients were recruited for the study. Fifty of these patients had
      coronary artery disease only and were compared in a case-control manner to 50
      healthy controls matched for age and sex. The 25 other coronary patients had also
      symptoms in another atherosclerotic territory (cerebral, peripheral or both) and
      were also compared to 25 matched controls. Mean plasma homocysteine level was
      significantly higher in coronary patients than in controls (11.7 +/- 0.7 mumol l
      1, n = 50 versus 9.9 +/- 0.5 mumol l-1, n = 50, p < 0.05). Homocysteine in
      patients with symptomatic atherosclerosis in two or three arterial sites was 15.7
      +/- 1.5 mumol l-1 which differed significantly from matched controls and from
      patients with coronary artery disease only (p = 0.01). The extent of coronary
      atherosclerosis evaluated by an angiographic coronary score correlated weakly to
      plasma homocysteine levels (r = 0.25, p < 0.05). The patients with both
      hypertension and high levels of homocysteine (> 11.3 mumol l-1, median value) had
      more severe coronary atherosclerosis (coronary score of 16.3 +/- 2.3 versus 11.9
      +/- 0.9, p < 0.05) and more diffuse atherosclerosis (number of atherosclerotic
      territories of 1.5 +/- 0.2 versus 1.2 +/- 0.7, p = 0.08) than the coronary
      patients without this association. There were no other high risk association when
      considering the other classical risk factors. Thus, the highest levels of
      homocysteine were present in patients with coronary disease and another
      symptomatic localisation of atherosclerosis. A small gradient in the extent of
      coronary atherosclerosis was found with increasing levels of homocysteine. The
      presence of both hypertension and hyperhomocysteinemia was associated with more
      severe coronary atherosclerosis.

PMID- 9261643
TI  - Acute pericarditis presenting with sinus bradycardia: a case report.
AB  - Acute pericarditis is almost invariably associated with sinus tachycardia. Recent
      onset chest pain in the presence of (sinus) bradycardia is considered to be
      associated with an acute ischemic syndrome rather than acute pericarditis. This
      report describes a patient with acute pericarditis initially presenting with
      sinus bradycardia, probably due to a vasovagal response to (chest) pain.

PMID- 9261642
TI  - Elevated Lp(a) is the most frequent familial lipoprotein disorder leading to
      premature myocardial infarction in a country with low cholesterol levels.
AB  - Disorders of the lipoprotein metabolism are an important cause of premature
      coronary artery disease and myocardial infarction. Of the genetic lipoprotein
      disorders, elevation of apoprotein (apo) B containing lipoproteins is the most
      frequent one in the western population. We aimed to define the prevalence of
      genetic lipoprotein disorders and other risk factors in a population from a
      country with a low average cholesterol levels. We examined 48 consecutive
      patients with premature myocardial infarction below age 55, their 78 siblings and
      age and body mass index matched controls for familial lipoprotein disorders. The
      patients with premature myocardial infarction had higher triglyceride, low
      density lipoprotein, apo B, lipoprotein (Lp) (a) and lower apo A1 levels then
      controls (p < 0.05). Of the nonlipid risk factors, 67% smoked, 8% had diabetes
      mellitus, 17% had hypertension and 58% a family history of premature coronary
      artery disease. Fifty percent of these patients with premature myocardial
      infarction had a familial lipoprotein disorder. Familial excess of Lp(a) was the
      most frequent lipoprotein abnormality present in 16% of the patients followed by
      familial combined hyperlipidemia. We conclude that, Lp(a) increase was the most
      frequent familial lipoprotein abnormality in this population. The frequency of
      familial lipoprotein disorders in this population emphasises the need to screen
      siblings of patients with premature myocardial infarction.

PMID- 9261644
TI  - Painless Prinzmetal's ST elevation related to propranolol: a case report.
AB  - Previous studies have shown that propranolol, an effective mainstay for angina
      pectoris and unstable angina, can induce coronary arterial spasm in patients with
      variant angina. However, no report has yet associated it with painless
      Prinzmetal's ST elevation in patients without a history of variant angina. The
      present communication describes such an unusual and negligible case after
      propranolol overdose. Coronary arterial spasm can be induced by beta-blocker, not
      only in patients with variant angina but also in normal persons.

PMID- 9261645
TI  - N-acetylcysteine infusion in viral myocarditis: a case report.
AB  - N-acetylcysteine improves survival in established acute liver failure following
      paracetamol overdose by reducing the incidence of multiorgan failure. These
      benefits are thought to be related to decreased tissue hypoxia by the enhancement
      of both oxygen delivery and oxygen extraction. Similar findings have been
      recorded in critically ill patients from an alternative aetiology. The
      cardiovascular properties of N-acetylcysteine are to increase stroke volume
      index, and thus cardiac output, although there is no effect on cardiac output in
      normal subjects. N-acetylcysteine is known to improve myocardial contraction in a
      hamster model of chronic myocardial ischaemia, but such effects have not
      previously been described in humans. We report the beneficial circulatory effect
      of N-acetylcysteine in a patient with marked left ventricular dysfunction
      secondary to acute viral myocarditis.

PMID- 9261646
TI  - Mitral valve repair-related hemolysis: a report of two cases.
AB  - Two patients are described who suffered from progressive intravascular hemolysis
      following different kinds of reconstructive surgery of the mitral valve. Within
      the context of increasing numbers of operations aimed to preserve the mitral
      valve, the importance and difficulty of prompt recognition and adequate treatment
      of this very uncommon but potential lethal complication are emphasised.

PMID- 9261647
TI  - Electrocardiographic criteria for the diagnosis of right ventricular involvement
      in the setting of acute inferior infarction.
AB  - Surface electrocardiograph of twelve cases of isolated left ventricular inferior
      infarction and 24 cases of biventricular inferior infarction confirmed by two
      dimensional echocardiography were analysed. ST segment elevation in lead III more
      than in lead II and ST segment depression in leads I and aVL were highly
      sensitive in diagnosing right ventricular involvement. ST segment depression in
      lead V3 equal to or greater than ST segment elevation in lead III was highly
      specific but had low sensitivity. These findings can be helpful in cases where
      right sided chest leads have not been recorded or are inconclusive.

PMID- 9261648
TI  - The nature and extent of body-image disturbances in anorexia nervosa and bulimia
      nervosa: a meta-analysis.
AB  - OBJECTIVE: Although body-image disturbance is among the diagnostic criteria for
      anorexia nervosa and bulimia nervosa, the nature and extent of this disturbance
      have not been precisely identified. This is the purpose of this first meta
      analysis of extant research on body image and eating disorders. METHOD: Using
      contemporary techniques, the meta-analysis systematically examined 66 studies
      (from 1974 to 1993) of perceptual and attitudinal parameters of body image among
      anorexics and bulimics relative to control groups. RESULTS: Attitudinal body
      dissatisfaction, both questionnaire and self-ideal discrepancy measures, produced
      substantially larger effect sizes than did perceptual size-estimation inaccuracy.
      Body dissatisfaction measures, whether global or weight/shape related,
      differentiated bulimic and anorexic groups (with bulimics having more
      dissatisfaction), whereas perceptual distortion indices did not. Somewhat larger
      effects occurred with whole-body than with body-part size-estimation assessments.
      Size distortion among patients with eating disorders appears unlikely to reflect
      a more generalized sensory/perceptual deficit. DISCUSSION: Scientific,
      conceptual, and clinical implications of these findings are delineated.

PMID- 9261649
TI  - Relationship of weight, body dissatisfaction, and self-esteem in African American
      and white female dieters.
AB  - OBJECTIVE: The present study examined the relationship among weight, body
      dissatisfaction, and self-esteem in a large group of African American and white
      female dieters who were generally overweight and of middle to high socioeconomic
      status. METHOD: Subjects were participants in a survey of dieting practices
      undertaken by Consumer Reports magazine. Major outcome measures included the
      Rosenberg Self-Esteem Scale and an assessment of shape and weight attitudes.
      RESULTS: No significant differences between African American and white women were
      found for body dissatisfaction, self-esteem, discrepancies between actual and
      ideal weight and shape, or the relationship between self-esteem and body
      dissatisfaction. Body mass index contributed less to body satisfaction scores in
      African American than in white women. DISCUSSION: This study provides a
      comparison of African American and white women in the upper social classes, and
      raises the possibility that previous findings of less body concern in African
      American women reflect class rather than race effects.

PMID- 9261650
TI  - Eating-disordered behavior in males: the impact of adverse childhood experiences.
AB  - OBJECTIVE: The authors examined the possible relationship of childhood sexual
      abuse, physical abuse, and dysfunctional family background and the risk for
      developing an eating disorder in adult males. METHOD: Several anonymous
      questionnaires were distributed to male university students. RESULTS: Of the 301
      men, 12 (4.0%) had experienced childhood sexual abuse, 11 (3.6%) had been victims
      of physical abuse, 79 (26.2%) reported an adverse family background, and 14
      (4.6%) had an increased risk for developing an eating disorder. There were no
      significant differences in the risk for developing an eating disorder and in
      total EDI between victims and nonvictims, but a significantly increased risk for
      eating disorders in men with an adverse family background. DISCUSSION: The
      findings suggest that long-lasting negative familial relationships, particularly
      in connection with physically abusive experiences, may increase the risk for
      eating disorders.

PMID- 9261651
TI  - Sex differences in the relationship of body fat distribution with psychosocial
      variables.
AB  - OBJECTIVE: This study tested the hypothesis that the relationship of psychosocial
      variables to body fat distribution would differ in men and women and would vary
      according to gender differences in natural patterns of fat distribution. METHOD:
      Body fat distribution and psychological functioning were examined in 5,930 male
      and 7,598 female dieters. RESULTS: Upper body size and shape were more strongly
      related to psychological functioning in men and lower body size and shape were
      more important in women. DISCUSSION: To better understand the association of
      weight with psychosocial status, patterns of body fat distribution should be
      considered.

PMID- 9261652
TI  - Eating disorders in adolescence in a Swiss epidemiological study.
AB  - OBJECTIVE: This is a study of prevalence rates for anorexia nervosa (AN) and
      bulimia nervosa (BN) in an epidemiological sample of Swiss adolescents. METHOD: A
      two-stage approach was used which involved the screening of a large sample of
      adolescents aged 14-17 and subsequent interviews of screen-positive and control
      subjects. RESULTS: The prevalence rates for adolescent girls were 0.7% for AN and
      0.5% for BN. DISCUSSION: Full clinical syndromes of AN and BN in adolescents are
      by far less frequent than individual symptoms of eating disorders. There is more
      cross-cultural variation for prevalence rates in BN than in AN.

PMID- 9261653
TI  - A comparison of psychopathology in eating disorder patients from France and the
      United States.
AB  - OBJECTIVE: This study compares Minnesota Multiphasic Personality Inventory (MMPI)
      profiles of subtypes of eating disorder patients in France and the United States.
      METHOD: The patients were hospitalized in psychiatric hospitals in France and the
      United States. Diagnoses were made by independent clinicians who reviewed the
      clinical material. The 550-item version of the MMPI was administered to the US
      subjects; and a 357-item version to the French. RESULTS AND DISCUSSION: In both
      the US and French subjects, more psychopathology was found in the groups
      diagnosed with both anorexia nervosa and bulimia nervosa than in those with
      either anorexia nervosa or bulimia alone, consistent with previous research. The
      US subjects had generally more psychopathology than the French, except in the
      anorexia-restrictor subgroup.

PMID- 9261654
TI  - Childhood-onset anorexia nervosa: towards identifying a biological substrate.
AB  - OBJECTIVE: The etiology of anorexia nervosa is not fully understood, but is
      probably multifactorial, including a biological substrate. The purpose of this
      paper is to investigate the possible underlying biological substrate. METHOD:
      Fifteen children and adolescents aged 8-16 years underwent regional cerebral
      blood blow radioisotope scans. All fulfilled DSM-IV criteria for anorexia
      nervosa. Three of the girls had a follow-up scan when they had regained their
      lost weight. RESULTS: Thirteen of the 15 patients had unilateral temporal lobe
      hypoperfusion, 8 on the left side and 5 on the right. The abnormality persisted
      in the 3 girls who had a follow-up scan after weight restoration. DISCUSSION:
      This is the first report of reduced regional cerebral blood flow in childhood
      onset anorexia nervosa, and suggests an underlying primary functional
      abnormality.

PMID- 9261655
TI  - Primary prevention of eating disorders: might it do more harm than good?
AB  - OBJECTIVE: The aim of this pilot study was to evaluate a new school-based eating
      disorder prevention program designed to reduce dietary restraint. METHOD: Forty
      six school-girls, aged 13-14 years, took part. The intervention consisted of
      eight weekly sessions of 45 min duration. A battery of self-report questionnaires
      was administered before and after the intervention and 6 months later. RESULTS:
      Unlike previous prevention studies, there was not only an increase in knowledge
      at postintervention but there was also a decrease in target behavior and
      attitudes. However, these effects were short-lived since they had disappeared 6
      months later: indeed, at 6-month follow-up there was an increase in dietary
      restraint compared with baseline. DISCUSSION: These findings suggest that the
      intervention had been counterproductive since it led to an increase in dietary
      restraint. They imply that school-based prevention programs may do more harm than
      good.

PMID- 9261656
TI  - A controlled study of trait narcissism in anorexia and bulimia nervosa.
AB  - INTRODUCTION: Many theories attribute anorexia and bulimia nervosa to
      "pathological narcissism," but this conception has not been adequately evaluated.
      METHOD: We compared the scores of 90 eating disorder (ED) sufferers (23 anorexic
      restricters, 14 anorexic bingers, and 53 bulimics) with those of 36 psychiatric
      control (PC) and 54 normal-control (NC) females on validated self-report scales
      measuring Narcissism, Affective Instability, Stimulus Seeking, Compulsivity, and
      Restricted Expression. RESULTS: Narcissism scores of ED patients (whether
      restricters or bingers/purgers) consistently exceeded those of the PC and NC
      cases, suggesting that Narcissism does indeed load more heavily in the EDs than
      in other psychiatric disturbances. Conversely, Affective Instability was
      characteristic of all clinical cases (i.e., of EDs and PCs), Restricted
      Expression and Compulsivity were characteristic of restricters, and Stimulus
      Seeking was characteristic of bingers/purgers. DISCUSSION: Results are consistent
      with the notion that different ED variants may reflect subtype-specific
      temperaments and/or adaptive styles acting-upon shared underlying narcissistic
      disturbances.

PMID- 9261657
TI  - An examination of subtype criteria for bulimia nervosa.
AB  - OBJECTIVE: We examined the new subtyping criteria for bulimia nervosa by
      comparing purging and nonpurging bulimia nervosa patients with two similar
      subgroups: binge eating disorder patients and an eating disorder not otherwise
      specified (ED-NOS) group who compensates but does not binge eat or meet weight
      criteria for anorexia, which we labeled compensatory eating disorder (CED). Of
      particular interest was whether purging could differentiate a more "disturbed"
      group of patients, bulimic or otherwise. METHOD: We compared these four subgroups
      on the Eating Disorders Inventory (EDI), the Hopkins Symptom Checklist (SCL-90R),
      and rates of hospitalization. RESULTS: There were few differences between either
      the purging or nonpurging bulimic patients, or the CED patients. All three groups
      showed more comorbid disturbance than the binge eating patients. DISCUSSION: The
      findings failed to support the current subgrouping criteria for purging and
      nonpurging bulimia nervosa but indicated the need for further revision in the
      Diagnostic and statistical manual of mental disorders and the possible creation
      of a subgroup based on compensatory behaviors.

PMID- 9261658
TI  - Patterns of food selection during binges in women with binge eating disorder.
AB  - OBJECTIVE: The aim of this study was to determine whether temporal patterns of
      food selection during binges in obese subjects with binge eating disorder (BED)
      differ from those of patients with bulimia nervosa (BN). METHOD: Ten obese women
      with BED and 10 weight-matched women without BED each consumed a multiple-item
      meal identical to that used in previous studies with bulimics, and all subjects
      were instructed to binge. An experimenter recorded the subjects' food choices
      every 10 s throughout the meal via a closed-circuit TV camera. RESULTS: Subjects
      with BED consumed significantly more meat than subjects without BED (397.78 vs.
      270.64 kcal), but the food choices and percentages of time spent eating each of
      the foods were similar among BED, non-BED, and normal weight controls. While
      bulimics ate dessert foods earlier in the meals, all other groups ate meat
      towards the beginning of their meal and ate more dessert foods towards the end of
      the meal. DISCUSSION: Food selection patterns during binges in subjects with BED
      are more similar to eating patterns of noneating disordered subjects, than to
      patterns seen in patients with BN. These data suggest that binge episodes between
      different groups of eating-disordered populations are qualitatively different.

PMID- 9261659
TI  - Initial manifestations of disordered eating behavior: dieting versus binging.
AB  - OBJECTIVE: We examined the onset of binge eating and dieting in 108 women with
      bulimia nervosa to determine whether (1) dieting always preceded binge eating;
      (2) dieting always preceded the onset of bulimia nervosa; and (3) individuals who
      manifested early initial binge eating differed from those whose earliest
      manifestation of disordered eating behavior was dieting in terms of lifetime
      psychopathology and temperament. METHOD: One hundred eight women were assessed at
      entry to a randomized clinical trial of cognitive-behavioral therapy for bulimia
      nervosa using structured diagnostic methodology. Retrospective recall of the
      onset of disordered eating behavior was used to categorize individuals as initial
      binge eaters or initial dieters. We then compared lifetime psychopathology and
      temperament across the two groups. RESULTS: Seventeen percent of women reported
      early binge eating prior to any dieting behavior. The mean age of onset of
      binging in this group was approximately 10 years. Neither the clinical picture of
      bulimia nervosa nor lifetime psychopathology differed between initial binge
      eaters and initial dieters. Individuals with early binge eating endorsed higher
      novelty seeking and lower harm avoidance. CONCLUSION: In a minority of women with
      bulimia nervosa, binge eating precedes dieting. These women display markedly
      higher novelty seeking and lower harm avoidance. Possible links between the
      dopamine system, novelty seeking, and appetitive behavior are discussed.

PMID- 9261660
TI  - A multicenter evaluation of a proprietary weight loss program for the treatment
      of marked obesity: a five-year follow-up.
AB  - OBJECTIVE: The traditional goal of obesity therapy has been the reduction of body
      weight to an ideal standard. Patient difficulties, however, in reaching this goal
      have led to a reassessment of weight loss criteria. The Institute of Medicine of
      the National Academy of Sciences recently proposed that successful long-term
      weight loss be defined as the reduction of initial weight by 5% or more and the
      maintenance of this loss for at least 1 year. The present study used these
      criteria to evaluate the long-term efficacy of a proprietary weight loss program.
      METHODS: Patients were 621 persons who had completed a 26-week weight loss
      program that included 12 weeks of treatment by a very-low-calorie diet. They were
      recruited from a total of 1,283 eligible persons who had been treated at 36
      clinics nationwide. Clinics were randomly selected to participate. Patients'
      weights were determined in telephone interviews initially conducted 2 years after
      treatment and then at yearly intervals through 5 years of follow-up. RESULTS: At
      the end of treatment, men achieved a mean reduction in initial weight of 25.5 +/-
      1% and women 22.6 +/- 1%. Subjects regained substantial amounts of weight by the
      2-year follow-up but 77.5% of men and 59.9% of women still maintained losses of
      5% or more of body weight. At the 3-year follow-up, 53% of the original sample
      (of 621 persons) maintained losses of 5% or more and 35% losses of 10% or more.
      These trends were apparent 4 and 5 years after treatment but the dwindling sample
      sizes prevented definitive assessments. DISCUSSION: The findings showed that a
      program of lifestyle modification combined with the brief use of a very-low
      calorie diet was associated with successful weight control in a substantial
      portion of patients several years after treatment. Long-term weight losses of 5%
      or more of initial weight are likely to be associated with improvements in health
      complications.

PMID- 9261662
TI  - Eating disorders and panic: four cases of pathological coping.
AB  - Four cases demonstrate the intensification of distress when coping triggers panic
      and pathological eating. In all four cases, eating-disordered patients attempt to
      alleviate panic with food, and instead exacerbate both the panic and eating
      disorder symptomatology. Implications for the assessment and treatment of persons
      diagnosed with panic disorder and an eating disorder are presented.

PMID- 9261661
TI  - Adult obesity and functioning in the family of origin.
AB  - OBJECTIVE: This study investigated the relationship between eating and weight
      behaviors and functioning in individuals' families of origin. METHOD: Subjects
      were 237 women and 242 men enrolled in the RENO (Relationship of Energy,
      Nutrition, and Obesity) Diet-Heart Study, a prospective 5-year study of the
      effects of weight fluctuation on cardiovascular disease risk factors in normal
      weight and obese adults. Variables of primary interest included subjects' body
      mass index (BMI), age of onset of obesity, eating attitudes, lack of control
      while eating, and family functioning. RESULTS: In men, higher family cohesion was
      related to healthier eating attitudes and better control over eating, controlling
      for age, BMI, and adaptability, whereas higher adaptability (changing rules and
      poor leadership) was related to earlier onset of obesity and more disturbed
      eating attitudes. Cohesion and adaptability were not related to body weight or
      eating variables in women. DISCUSSION: The lower societal pressure on men to be
      thin may increase the importance of family factors in influencing their shape and
      weight.

PMID- 9261663
TI  - Benchmarks of social treatment for children with autism.
AB  - Data on the social behavior of typical children may inform practitioners and
      researchers regarding the appropriate goals of intervention for children with
      autism. This study assessed the ongoing levels of naturally occurring social
      behavior in 64 preschool-aged children. A 2 x 2 factorial design was used to
      analyze population (children with autism and typical children) and age (3 years 3
      months vs. 4 years 4 months) differences at the time of preschool entry.
      Predictable population differences were found for key social behaviors of
      proximity to children, social bids from children, and focus of engagement on
      children, as well as for behavioral context variables of verbalizations, adult
      focus, and atypical behaviors. No differences were found in the amount of time
      spent focused on toys or objects. There were also no differences in the
      presenting behaviors of younger and older children with autism. Results are
      discussed in terms of implications for establishing early social intervention
      goals.

PMID- 9261664
TI  - Imitation of pretend play acts by children with autism and Down syndrome.
AB  - Although there has recently been considerable research interest in the
      difficulties that children with autism have engaging in pretend play, little
      attention has been paid to the ability of these children to imitate pretend play
      acts. Furthermore, suggestions that children with Down syndrome have relatively
      advanced abilities in pretend play have not been accompanied by an examination of
      their capacity to imitate pretend play. Three groups of children: autistic, Down
      syndrome, and normally developing were studied for their capacity to imitate
      single pretend acts and a series of pretend acts that formed scripts. While the
      children with autism were surprisingly better than the other two groups on the
      single-scheme task, they demonstrated specific difficulties on the multischeme
      task. Results are discussed in relation to current theories of autism and the
      notion of imitation.

PMID- 9261665
TI  - An investigation of attention and affect in children with autism and Down
      syndrome.
AB  - Longitudinal videotape recordings of six young children with autism and six age-
      and language-matched children with Down syndrome in structured play with their
      mothers at home were coded for the focus of the child's visual attention for four
      bimonthly visits and for facial affect for two of the four visits. The main
      finding was that the children with autism showed reduced expression of positive
      affect in a familiar social context. The autistic group attended to the mother's
      face and the researchers only about half as much as the Down syndrome group, but
      these differences did not reach statistical significance. Compared to the Down
      syndrome group, the autistic group displayed a smaller proportion of their total
      positive affect toward the mother's face and toward the researcher, but only the
      latter group difference reached statistical significance. Although limited by the
      small sample size, these findings suggest that autistic children's known deficits
      in attention and affective responsiveness to others persist even in structured
      interactions with a familiar partner in the home.

PMID- 9261666
TI  - Sociosexual knowledge, experience, attitudes, and interests of individuals with
      autistic disorder and developmental delay.
AB  - Thirty-one individuals, 15 with autistic disorder and 16 with developmental
      delay, male and female, were asked to select from a series of drawings depicting
      sexually relevant activities and to define them. In addition they were asked to
      describe their sexual experiences, attitudes, and interests, using a
      semistructured interview format. Ability to select through pointing out sexually
      relevant body parts or activities was not different by level of functioning,
      group, or gender. There were differences in providing a sociosexual label,
      however, with better performance for those with developmental delay and for the
      higher functioning. No differences were evident for sexual experiences, likely
      because of the considerable variability across subjects and types of activity,
      with some individuals reporting very many and others very few. As to attitudes,
      individuals with autistic disorder endorsed more sexual activities than those
      with developmental delay. Higher knowledge of sexuality terms and activities was
      inversely related to their endorsement. Literalness and perseveration were
      evident in the responses of some, primarily those with autistic disorder. Results
      are discussed for their relevance to the reliability and validity of information
      on sexual awareness among the developmentally disabled. Suggestions for future
      research are offered.

PMID- 9261667
TI  - Autistic behaviors among girls with fragile X syndrome.
AB  - Reports of autistic behaviors were examined for 30 school-age girls with fragile
      X (fraX) and 31 age- and IQ-matched controls through a structured interview
      administered to each girl's parent(s). IQ scores were obtained for each
      participant; anxiety, neuroanatomical, and molecular-genetic data were derived
      for girls with fraX. Girls with fraX had significantly more autistic behaviors
      than controls. These behaviors were qualitatively similar to those reported for
      boys with fraX, but were not correlated with IQ. Anxiety in girls with fraX was
      positively correlated with abnormal social and communication behaviors; posterior
      cerebellar vermis area was negatively correlated with measures of communication
      and stereotypic/restricted behaviors. Severity of stereotypic/restricted
      behaviors was negatively correlated with the prevalence of active non-fraX
      chromosomes. Thus anxiety and posterior cerebellar area measures had distinct
      associations with subsets of autistic behaviors; these associations may have
      important implications for understanding the neurobiology of autism.

PMID- 9261668
TI  - Sign language and motor functioning in students with autistic disorder.
AB  - Sign language production of 14 low-functioning students diagnosed with autistic
      disorder was examined. Videotapes of the students signing with their teachers
      were analyzed for frequency and accuracy of sign location, handshape, and
      movement production. The location aspect of signs was produced more accurately by
      the subjects than either the handshape or movement aspects. Wide individual
      differences were evident among the students in the number of signs they produced,
      accuracy of sign formation, and performance on measures of motor functioning.
      Students' sign vocabulary size and accuracy of sign formation were highly
      correlated with their performance on two measures of apraxia and with their fine
      motor age scores.

PMID- 9261670
TI  - Brief report: risperidone for severely disturbed behavior and tardive dyskinesia
      in developmentally disabled adults.

PMID- 9261669
TI  - High-dose pyridoxine and magnesium administration in children with autistic
      disorder: an absence of salutary effects in a double-blind, placebo-controlled
      study.
AB  - Several reports have described salutary effects such as decreased physical
      aggression and improved social responsiveness being associated with the
      administration of high doses of pyridoxine and magnesium (HDPM) in open-labeled
      and controlled studies of patients with autism. Despite this fact, this
      intervention remains controversial. A 10-week double-blind, placebo-controlled
      trial was undertaken to examine both the efficacy and safety of HDPM in autism.
      Twelve patients were enrolled, and 10 patients (mean age 6 years 3 months) were
      able to complete the study. HDPM at an average dose of 638.9 mg of pyridoxine and
      216.3 mg of magnesium oxide was ineffective in ameliorating autistic behaviors as
      assessed by the Children's Psychiatric Rating Scale (CPRS), the Clinical Global
      Impression Scale, and the NIMH Global Obsessive Compulsive Scale. Furthermore, no
      clinically significant side effects were noted during HDPM administration. A
      trend for a transient change on the CPRS was found that was possibly due to a
      placebo response. This study raises doubts about the clinical effectiveness of
      HDPM in autistic disorder.

PMID- 9261672
TI  - Autism and the inferior colliculus.

PMID- 9261671
TI  - Obstetrical suboptimality in autistic children: an Italian sample.

PMID- 9261673
TI  - What is PDD-NOS and how is it diagnosed?

PMID- 9261674
TI  - Glass peek composite promotes proliferation and osteocalcin production of human
      osteoblastic cells.
AB  - An isoelastic intramedullary implant has been developed using a composite of
      polyetheretherketone and 10% random, chopped E-glass fibers (GPEEK). The effect
      of this novel material on human bone cells has not been defined. The objective of
      this study was to test whether GPEEK supported the proliferation of the human
      bone cell line MG63, which exhibits osteoblastlike characteristics. Cells (1 x
      10(5)/mL) were propagated on GPEEK discs with three different surface roughnesses
      (3, 6, and 9 microns) and on polystyrene plates, for comparison. The reaction of
      MG63 osteoblastlike cells to the GPEEK polymer composite was analyzed by
      determination of cell yield, osteocalcin production, and levels of alkaline
      phosphatase. The viable cells that were retrieved from the GPEEK discs of all
      three surface roughness had an approximate sixfold increase in number.
      Osteoblastic function of the cells, indicated by osteocalcin production, was
      unimpaired after a 5-day culture on the three surfaces of GPEEK. The highest
      level of osteocalcin was produced by osteoblastic cells propagated on GPEEK with
      a 9 microns surface roughness. The levels of alkaline phosphatase of these cells
      were similarly greater for the different degrees of surface roughness. Overall,
      this study demonstrates that GPEEK supported proliferation of osteoblastlike
      cells and provided a favorable environment for the continued production of
      osteocalcin in vitro.

PMID- 9261675
TI  - Effect of Ni ions on expression of intercellular adhesion molecule 1 by
      endothelial cells.
AB  - Previous studies have shown that Ni-based alloys implanted into soft tissues
      cause an infiltration of inflammatory cells around the implant. This phenomenon
      is potentially important to dental alloys which are adjacent to oral tissues. To
      help define the mechanisms by which Ni causes an infiltration of inflammatory
      cells, we exposed endothelial cells in vitro to Ni ions and measured the
      expression of intercellular adhesion molecule 1 (ICAM-1). ICAM-1 is known to be
      involved in the recruitment of inflammatory cells from the bloodstream. We also
      exposed macrophages to Ni ions to test the hypothesis that Ni might alter
      cytokine secretion and subsequently cause expression of ICAM-1 on endothelial
      cells. The results showed that Ni ions could promote the expression of ICAM-1 on
      endothelial cells, but only at concentrations which were high enough (850 mumol/L
      for 24 h) to suppress cell metabolic activity. Although we had previous evidence
      that Ni could cause macrophages to secrete cytokines such as interleukin 1 beta,
      Ni-exposed macrophage supernatants did not induce expression of ICAM-1 on
      endothelial cells at concentrations subtoxic to the macrophages (85 mumol/L). At
      subtoxic concentrations, Ni ions were able to suppress ICAM-1 expression on
      endothelial cells which were stimulated with lipopolysaccharide. Thus, Ni ions
      either promoted or suppressed the expression of ICAM-1 depending on their
      concentration. This dual action of Ni ions may be important in vivo where a
      gradient of concentrations of released ions is likely to exist around the
      implanted biomaterial. Further studies are necessary to determine the effect of
      time of exposure and the molecular mechanisms of increased ICAM-1 expression.

PMID- 9261676
TI  - Quantitative comparison of shear-dependent Staphylococcus aureus adhesion to
      three polyurethane ionomer analogs with distinct surface properties.
AB  - Bacterial adhesion is a central step in infection on biomaterial surfaces;
      however, the relation between biomaterial surface properties and adhesion remains
      poorly understood. To quantitatively determine the relationship among
      polyurethane surface properties, protein coating, and adhesion, we have compared
      attachment and detachment kinetics of Staphylococcus aureus on three different
      novel polyurethanes with different protein coatings. Rate constants for
      attachment or detachment were measured as a function of shear rate in a well
      defined laminar flow field. The tested polyurethanes included a relatively
      hydrophobic-base polyether urethane and hydrophilic anionomer and cationomer
      analogs of the base material. Materials were tested bare, or coated with human
      fibrinogen, plasma, or albumin. The results suggest that the presence of
      fibrinogen or plasma greatly enhance the attachment rate constants and decrease
      the detachment rate constants on all materials. The most extreme differences
      among the different materials were observed on the bare materials, with the base
      polyurethane being most resistant to both attachment and detachment. However,
      except for a reduced attachment rate constant on the plasma-coated sulfonated
      polyurethane, few differences in the rate constants were observed among protein
      coated materials, suggesting the primary role of surface properties is masked by
      the presence of the adsorbed protein layer.

PMID- 9261677
TI  - A new anti-infective collagen dressing containing antibiotics.
AB  - A new antibacterial dressing for infected wounds was prepared. The dressing was
      composed of a collagen membrane and collagen sponge; both biomaterials possess
      good tissue biocompatibility. An active antibacterial layer of limited
      hydrophobicity was placed between the membrane and the sponge and into the upper
      part of the sponge. The dressing contained gentamycin or amikacin at
      concentrations of 0.3 microgram/cm2 (loading level of the drug utilized during
      preparation of the dressing). Either the antibiotic or its concentration easily
      can be changed in the dressing by the manufacturer. The dressing was stable for
      several months. The antibiotic was released slowly from the dressing in in vitro
      experiments for 3 days. Antibacterial activity of the dressing was tested using a
      mouse wound model experimentally infected with Pseudomonas aeruginosa. Both
      dressings, containing either amikacin or gentamycin, reduced the number of living
      bacterial cells in the infected tissue almost to zero during the course of
      observation. The new dressing may be effective in the treatment of infected
      wounds in patients.

PMID- 9261678
TI  - Porous bioactive glass and hydroxyapatite ceramic affect bone cell function in
      vitro along different time lines.
AB  - We describe the effects on cell function of treating porous bioactive glass (BG)
      such that its surface is a composite of carbonated hydroxyapatite and serum
      protein. The effects on bone cell function of porous hydroxyapatite (HA) ceramic
      and porous glass treated to become amorphous calcium phosphate only also were
      studied subsequent to their having adsorbed a serum protein layer. Substrates
      treated for different durations were seeded with MC3T3-E1 cells and cultured for
      3-17 days. Whereas cells seeded on any substrates, BG and HA produced collagen
      types I and III, bone sialoprotein, and osteopontin, there were significant
      differences between HA and BG, and among the various surface conditions created
      on BG. Covering the glass surface with hydroxyapatite and serum protein enhanced
      expression of high alkaline phosphatase activity, high rates of cell
      proliferation, and production of mineralized extracellular matrix. The
      enhancement may be due to the adsorption of a high quantity of fibronectin from
      the serum onto the reacted bioactive glass surface.

PMID- 9261679
TI  - Reduced protein adsorption on plastics via direct plasma deposition of
      triethylene glycol monoallyl ether.
AB  - The direct plasma-induced deposition of tri(ethylene glycol) monoallyl ether is
      reported. RF plasma polymerization of this monomer was carried out under both
      continuous wave (CW) and pulsed plasma operation. The major focus of this work
      was optimization of the degree of retention of the C-O-C bonds of the starting
      monomer during the deposition process. This successfully was accomplished using
      low RF power during the CW runs and low RF duty cycles during the pulsed plasma
      experiments. Spectroscopic analysis of the plasma films revealed a strong
      dependence of film composition on the RF power and duty cycles employed. In
      particular, an unusually high level of film chemistry compositional control was
      demonstrated for the pulsed plasma studies, with film composition varying in a
      steady, progressive fashion with sequential changes in the ratios of plasma on to
      plasma off times. This film chemistry controllability is demonstrated despite the
      relatively low volatility of the starting monomer. The utility of this plasma
      deposition approach in introducing polyethylene oxide (PEO) structures on solid
      substrates was evaluated via protein adsorption studies. Radiolabeled bovine
      albumin adsorption was studied on plasma-modified poly(ethylene teraphthalate)
      (PET) substrates. Dramatic reductions in both initial adsorption and retention of
      this protein were observed on PET samples having maximal PEO content relative to
      its adsorption on untreated PET surfaces. Good stability and adhesion of the
      plasma films to the underlying PET substrates were observed, as evidenced from
      prolonged immersion of plasma-treated surfaces in aqueous solution. Overall, the
      results obtained from the present work provide additional support for the utility
      of one-step plasma process to reduce biological fouling of surfaces via
      deposition of PEO surface units.

PMID- 9261680
TI  - Effect of methacrylic acid:methyl methacrylate monomer ratios on polymerization
      rates and properties of polymethyl methacrylates.
AB  - Five binary formulations were prepared from methyl methacrylate (MMA) and
      methacrylic acid (MAA) monomers, and six ternary formulations were prepared from
      polysols of 30% wt polymethyl methacrylate (PMMA)/MMA and MAA. Using thermal
      analyses (DSC and TGA) the polymerization kinetics, condition of postcuring,
      relative amount of residual monomers, and glass transition temperature (Tg) were
      determined. From bar-shaped samples, 25 x 5 x 0.9 mm in dimensions, mechanical
      properties [flexural moduli (E) and maximum strengths (sigma)] were measured in
      three-point bending. Polymerization kinetics of binary formulations improved over
      pure PMMA (from 15 to 4 min) as a result of over a 60-fold increase in
      propagation-to-termination constants (Kp/Kt) of MAA/MMA. The further addition of
      PMMA increased the viscosity, slowed down termination, and, consequently,
      improved the polymerization kinetics twofold. These enhancements occurred without
      a substantive change in the Tg of the ternary system (ca. 107 degrees C) over
      pure PMMA (ca. 112 degrees C). Moreover, the Es of the four ternary formulations
      averaged 2.94 GPa, which was comparable with many values reported in the
      literature. In contrast the sigma s of these same formulations averaged 97 MPa,
      which was about 25% better than earlier investigations of pure acrylic. When a
      thermoplastic material is required for pultruding profiles that cure fast and
      have good thermal-mechanical properties, ternaries of PMMA/MMA/MAA should be
      considered.

PMID- 9261681
TI  - Development and characterization of an alginate-impregnated polyester vascular
      graft.
AB  - Alignate gels are known to be biocompatible, degradable, and nontoxic. In this
      study, sodium alginate was impregnated into a porous, knitted polyester graft
      (Microvel double velour graft) 6 mm in diameter. The alginate-impregnated graft
      was investigated in vitro and in vivo to evaluate its potential for use as a new
      vascular graft impervious to blood, while retaining high porosity for tissue
      ingrowth and biological healing. For in vitro investigation, the coating weight,
      water permeability, morphology, and mechanical properties of the alginate
      impregnated grafts were compared to those of control or commercially available
      collagen-impregnated (Hemashield) grafts. The water permeability of the controls
      (1846 mL/min.cm2 at 120 mm Hg) was reduced > 99% by the alginate impregnation,
      rendering the graft impervious to blood. The coating weight of the alginate was
      45 mg/g of graft, producing a much lower value than that of the collagen
      impregnated model (310 mg/g). For in vivo investigation, the alginate-impregnated
      grafts were implanted in the aorta of mongrel dogs without preclotting for
      scheduled periods ranging from 4 h to 6 months. The control grafts after
      preclotting and the collagen-impregnated grafts without preclotting were also
      implanted for 3 and 6 months for comparison. Gross observation of the explanted
      grafts and histologic examination of the representative sections were conducted
      for three types of grafts using a light microscope after hematoxylin-eosin
      staining. No significant differences were observed between the histologic
      appearance of the alginate-impregnated grafts and that of the preclotted and
      collagen-impregnated grafts in terms of the degree of inflammation, foreign-body
      giant cell reaction, and intimal fibrosis. Endothelial-like cells were present on
      the midsections of all the grafts after 3 months of implantation. The resorption
      rate of alginate impregnated into the graft was also examined after staining the
      sections with periodic acid-Schiff reagent, Toluidine blue, and Alcian blue,
      which are specific for alginates. The staining alginate was partially visible
      between the graft fabrics up to 1 month after implantation, but was completely
      resorbed after 3 months. This preliminary study demonstrated that the use of an
      alginate as a biological sealant instead of proteins such as collagen, gelatin,
      and albumin may be a feasible approach to developing imprevious textile arterial
      prostheses, since the proteins have been reported to be generally unstable, hard
      to obtain in pure forms, not easy to crosslink and control resorption rate, and
      difficult to render compatible with standard storage and sterilization
      procedures.

PMID- 9261682
TI  - Molecular orbital models of ring expansion mechanisms in the silica-carbon
      monoxide system.
AB  - The development of a zero net shrinkage dental restorative material based upon a
      polymer-bioactive glass composite requires a second-phase material that expands.
      This study details the mechanisms of silica ring expansion by reaction with
      carbon monoxide. Carbon monoxide was used as a model adduct to represent
      potentially active sites on the polymer phase of the dental restorative. Silica
      rings were used to model the bioactive-glass phase of the composite. The 3-, 4-,
      5-, and 6-"member" silica rings have been modeled using the Austin Method (AM1)
      semi-empirical molecular orbital calculations. The reaction pathways were
      determined for carbon monoxide (CO) reaction addition to each of the rings. The
      activation barriers (Ea) for the ring expansions were determined from the
      transition state geometries wherein only one imaginary eigenvalue in the
      vibration spectrum existed (a true saddle point). In each case the reaction
      pathway included the hydrogen bonding of CO with a silicon, exothermic
      pentacoordinate bonding to silicon by the CO and weakening of the Si-O bridging
      bonds of the ring, and, finally, the incorporation of CO into the ring, forming a
      silica-carbonate ring. The activation for the ring expansions are +4.3, +6.1,
      +7.0, and -2.9 Kcal/mol for 3-, 4-, 5-, and 6-"member" silica rings,
      respectively. The volumetric expansion of the silica was estimated based upon the
      dilation of adjacent silicon-silicon atomic distances. The dimensional change was
      calculated to be 3.9%, 21.3%, 19.4%, and 24.2% for 3-, 4-, 5-, and 6-membered
      silica-carbonate rings, respectively.

PMID- 9261683
TI  - Reduced plaque accumulation on hydrocarbon thin film deposited on restorative
      acrylic polymers.
AB  - The deposition of a thin polymeric film from ethylene plasma was used to modify
      the surface properties of acrylic teeth, commonly used in the dental practice for
      crown and bridge restorations. The effects of the surface modification process on
      the surface composition, morphology, and energetics were evaluated by electron
      spectroscopy for chemical analysis, atomic force microscopy, and contact angle
      measurement respectively. Plaque accumulation on the plasma-coated and untreated
      material was evaluated in in vivo experiments, in which the same patient received
      conventional and plasma-coated restorations. The hydrocarbon-like surface of the
      plasma-coated restoration remained remarkably free from plaque, even in the
      absence of brushing. On the other hand, plaque accumulation was observed on the
      unmodified restoration. Results are discussed according to recent theories on
      bioadhesive phenomena.

PMID- 9261684
TI  - The effect of hard segment size on the hydrolytic stability of polyether-urea
      urethanes when exposed to cholesterol esterase.
AB  - Previous studies have shown that both polyester and polyether-based polyurea
      urethanes are susceptible to cleavage by hydrolytic enzymes. Furthermore, it has
      been hypothesized that the degree of hard segment micro-domain formation in
      polyurethane materials, as well as its structure, influences the ability of
      enzymes to degrade the polymers. The current study has investigated a series of
      segmented polyether-urea-urethanes synthesized with the same reagents but having
      different hard segment content. Using these materials, the relationship between
      the formation of hard segment domains and the hydrolysis of urea/urethane groups
      was specifically addressed. Both differential scanning calorimetry and X-ray
      photo-electron spectroscopy data indicated that the three materials differed
      significantly in the extent of hard segment domain formation and the nature of
      the chemical groups located in the top 10 nm of the surface. Biodegradation
      studies showed a strong dependence on hard segment domain formation and indicated
      that the polymer containing the highest number of hydrolytically labile urea and
      urethane bonds exhibited the least degradation. The ability of a polyurethane
      material to form hard segment micro-domains may contribute to the formation of a
      protective structure for the hydrolysable hard segment linkages located within
      the micro-domains.

PMID- 9261685
TI  - Variations in solution chemistry during calcium-deficient and stoichiometric
      hydroxyapatite formation from CaHPO4.2H2O and Ca4(PO4)2O.
AB  - This study explores the mechanistic paths taken when calcium-deficient
      hydroxyapatite, CDHAp (Ca/P = 1.50), and stoichiometric hydroxyapatite, SHAp
      (Ca/P = 1.67), form by reaction between particulate calcium phosphate salts. The
      acidic reactant was CaHPO4.2H2O (DCPD) and the basic reactant was Ca4(PO4)2O
      (TetCP). Variations in pH, calcium and phosphate concentrations, and the solids
      present during apatite formation, were determined as functions of reaction
      temperature (25.0 degrees, 37.4 degrees, and 50.0 degrees C) and time. It was
      found that the dissolution of TetCP was rate limiting for both hydroxyapatite
      (HAp) compositions at all three temperatures. However, the retrograde solubility
      and incongruent dissolution of DCPD became increasingly important in influencing
      the kinetics as the reaction temperature was increased. An amorphous intermediate
      phase was observed regardless of the HAp stoichiometry. The solutions from which
      the SHAp formed approached equilibrium at much shorter reaction times (1-2 days)
      than those from which the CDHAp formed. The latter continued to display changes
      in pH and in calcium and phosphate concentrations for 6 months. CDHAp was shown
      to be a thermodynamically stable phase. The dissolution of CDHAp is incongruent,
      showing a Ca/P molar ratio in solution less than 0.5.

PMID- 9261686
TI  - Effect of water vapor pressure and temperature on the amorphous-to-crystalline HA
      conversion during heat treatment of HA coatings.
AB  - X-ray diffraction was used to characterize the increment of crystallinity of HA
      coatings after heat treatment. Coatings were heated over the temperature (T)
      interval of 300 degrees-460 degrees C with a partial water vapor pressure of 0.01
      MPa and 0.001 MPa. Heat treatment also was done in air, as a contrast. It was
      found that the ratio (n) of the increment of crystallinity to the crystallinity
      of the as-received HA coatings was more significant for the coatings heated in
      atmosphere with water vapor than for those heated in air. This ratio also
      increased with water vapor pressure. The logarithm of the ratio increased
      linearly with 1/T, indicating that the ratio is exponential to T. The reason
      might be that recrystallization of the amorphous phase is a diffusion controlled
      process; the nucleation rate and growth velocity of the crystallites are in
      proportion to the diffusion coefficient, which is exponential to the temperature
      (T). Incorporation of water vapor in the atmosphere during heat treatment may
      decrease the activation energy for diffusion, which helps raise the diffusion
      coefficient of the atoms. Thus recrystallization of the amorphous phase can be
      accelerated.

PMID- 9261687
TI  - In vivo biocompatibility and biostability of modified polyurethanes.
AB  - Modified segmented polyurethanes were examined for biostability and
      biocompatibility using an in vivo cage implant system for time intervals of 1, 2,
      3, 5, and 10 weeks. Two types of materials were used: polyether polyurethanes and
      polycarbonate polyurethanes. Two unmodified polyether polyurethanes (PEUU A' and
      SPU-PRM), one PDMS endcapped polyether polyurethane (SPU-S), and two
      polycarbonate polyurethanes (SPU-PCU and SPU-C) were investigated in this study.
      Techniques used to characterize untreated materials were dynamic water contact
      angle, stress-strain analysis, and gel permeation chromatography. Cellular
      response was measured by exudate analysis and by macrophage and foreign body
      giant cell (FBGC) densities. Material characterization, postimplantation, was
      done by attenuated total reflectance-Fourier transform infrared spectroscopy (ATR
      FTIR) in order to quantify biodegradation and scanning electron microscopy (SEM)
      to qualitatively describe the cellular response and biodegradation. The exudate
      analysis showed that the acute and chronic inflammatory responses for all
      materials were similar. Lower FBGC densities and cell coverage on SPU-S were
      attributed to the hydrophobic surface provided by the PDMS endgroups. The
      polycarbonate polyurethanes did not show any significant differences in cell
      coverage or FBGC densities even though the macrophage densities were slightly
      lower compared to polyether polyurethanes. By 10 weeks, biodegradation in the
      case of PEUU A' and SPU-PRM was extensive as compared to SPU-S because the PDMS
      endcaps of SPU-S provided a shield against the oxygen radicals secreted by
      macrophages and FBGCs and lowered the rate of biodegradation. In the case of
      polycarbonate polyurethanes, the oxidative stability of the carbonate linkage
      lowered the rate of biodegradation tremendously as compared to the polyether
      polyurethanes (including SPU-S). The minor amount of biodegradation seen in
      polycarbonate polyurethanes at 10 weeks was attributed to hydrolysis of the
      carbonate linkage.

PMID- 9261688
TI  - Association of human growth hormone and calcium phosphate by dynamic compaction:
      in vitro biocompatibility and bioactivity.
AB  - The association of therapeutic agents with biomaterials has been achieved through
      various techniques, such as coating of the ceramic block surface or drug
      incorporation into ceramics. The dynamic compaction method recently was developed
      to consolidate drug-loaded calcium phosphate powder without a sintering step. In
      the present work, human recombinant growth hormone was loaded on biphasic calcium
      phosphate powder and consolidated by a specific process of cold sintering
      (dynamic compaction). Analyses of the biocompatibility of compacted pellets
      (mouse L929 fibroblastic cell culture) and the bioactivity of the drugs released
      by them (growth hormone bioassay) were performed. This report demonstrates the
      biocompatibility of the compacts prepared by dynamic compaction. L929 cell
      proliferation was maintained and the capacity to secrete fibronectin was
      conserved in the presence of compacted materials. Comparison of released growth
      hormone integrity, revealed by radioimmunoassay and eluted stain bioassay, has
      shown that the biological activity of growth hormone was totally preserved after
      dynamic compaction. However, 35% of loaded growth hormone was not released in our
      experimental conditions, probably because of the inaccessibility of growth
      hormone within the granulated compacts. Dynamic compaction shows good potential
      for the production of biomaterials capable of releasing therapeutic agents in
      situ.

PMID- 9261689
TI  - Assessment of bioactivity for orthopedic coatings in a gap-healing model.
AB  - In order to study bone growth conducting capacities of new biomaterials under
      standardized conditions, a goat model was developed based on a canine model by
      Soballe. Titanium alloy implants with and without a hydroxyapatite coating were
      used as positive and negative controls, and these were implanted with a
      circumferential gap of one millimeter in the spongious bone of the knee condyles
      of two groups of four goats. These goats were sacrificed at 6 and 25 weeks. A
      second experiment was done on two groups of four goats with the same type of
      titanium alloy and hydroxyapatite-coated implants as controls and with Polyactive
      55-45 coated titanium alloy implants for testing. These goats were sacrificed at
      9 and 25 weeks, respectively. Qualitative and quantitative differences in gap
      healing were evaluated through light microscopy, and initiation and direction of
      bone apposition were determined with fluorescence microscopy. Apposition of bone
      was seen directly on all hydroxyapatite surfaces and on some of the noncoated
      titanium alloy surfaces. The difference between the percentage of bone growth on
      the titanium alloy implants and the hydroxyapatite-coated implants appeared to be
      divergent in time: the bone growth on the noncoated implants declined after 9
      weeks in contrast to the steady increase of bone growth on the hydroxyapatite
      coated implants towards the 25 week follow-up time (p = 0.02). No significant
      difference was found between the first and the second experiment: apposition of
      bone on the implants differed only 6.6% on a scale of 0% to 100%. Only scarce
      bone growth was seen on the polyactive-coated implants in this model. The newly
      tested Polyactive 55-45 coating apparently needs initial bone contact for bone
      bonding and therefore showed hardly any direct bone formation on its surface. The
      clear differences in the reaction of bone to the coated and noncoated implants in
      this goat study and the reproducibility of these reactions of bone to the
      different controls indicate the sensitivity of the currently used animal model
      and its suitability for use as a bioactivity assay.

PMID- 9261690
TI  - Factors influencing stability at the interface between a porous surface and
      cancellous bone: a finite element analysis of a canine in vivo micromotion
      experiment.
AB  - Several factors contribute to the success of stable bony ingrowth into the porous
      coated surfaces of orthopaedic implants used in hip arthroplasty. Despite having
      good bony apposition, bony ingrowth might not occur if the relative motion
      between bone and implant is large. Therefore, determining the limiting
      micromotion value that inhibits stable bony ingrowth is important. From a
      previous canine in vivo micromotion study performed at our laboratory, this
      limiting value was found to be 20 microns. Initially, cementless orthopaedic
      implants are stabilized only by frictional forces at the bone-implant interface.
      Therefore, other parameters such as the coefficient of friction and the
      compressive force normal to the interface should be considered as important
      factors which stabilize the interface along with micromotion. The purpose of this
      analytical study was to elucidate how the stability at the bone-implant interface
      is influenced by various factors, namely, motion of the implant, the coefficient
      of friction, the degree of pres fit, and the modulus of the surrounding
      cancellous bone in determining the stability of the bone-implant interface.
      Nonlinear and linear finite element models which simulated the immediate
      postsurgical condition and the end point of the canine in vivo micromotion
      experiment, respectively, were used to this end. From the results of the finite
      element models it was possible to identify the displacement magnitude for which
      the implant slipped relative to the bone as the motion of the implant was
      increased incrementally. This was done for combinations of the coefficient of
      friction, press fit, and Young's modulus of cancellous bone. This was used as an
      indicator of the limiting implant motion value beyond which bony ingrowth will be
      inhibited. The stress distribution in the surrounding cancellous bone bed was
      also obtained from the results of the finite element analyses for different press
      fit conditions. The results of the study indicated that under slight press-fit
      conditions, the implant slipped relative to bone for implant motions as low as 20
      microns. For higher degrees of press fit and reasonable values for the
      coefficient of friction, no slip occurred for implant motions as much as 100
      microns. Although higher degrees of press fit were theoretically conducive to
      better implant stability, the concomitant high stresses in the adjacent
      cancellous bone will tend to compromise the integrity of the press fit. This was
      also evident when the results of an analytical model with a lower degree of press
      fit correlated well with those of the canine in vivo experiment in which a higher
      press fit was used, suggesting a possibility of achieving a less than desired
      press fit during the process of implantation. Through this study the importance
      of factors other than implant motion was emphasized. The results of the study
      suggest that the limiting value of implant motion that inhibits bone ingrowth
      might vary with the degree of press fit for reasonable coefficients of friction.

PMID- 9261691
TI  - Statement letter in regard to use of animals in research.

PMID- 9261692
TI  - Insulin-like growth factor-I liposomal gene transfer and systemic growth hormone
      stimulate wound healing.
AB  - Many of the anabolic effects of growth hormone (GH) act through insulin-like
      growth factor-I (IGF-I). Systemic administration of GH in combination with IGF-I
      has been shown to stimulate wound reepithelialization, however, it causes
      hyperglycemia or hypoglycemia, respectively. We hypothesize that very low doses
      of IGF-I in a liposome form will have the same positive wound-healing effect when
      administered locally as the higher doses of GH plus IGF-I given systemically. To
      test this hypothesis, rats were given a 40% TBSA full-thickness scald injury and
      received either placebo IGF-I (5.0 mg/kg/day, subcutaneously), IGF-I liposome
      (0.9 microgram/kg/week, subcutaneously), or a combination of GH and IGF-I, or IGF
      I liposomes for 8 weeks. GH in combination with IGF-I showed a significant
      increase in postburn weight. Wound reepithelialization, measured by computerized
      planimetry as percentage original wound area, was significantly increased in rats
      receiving GH plus IGF-I, GH plus IGF-I liposomes, and IGF-I liposomes when
      compared to sham, or IGF-I (p < 0.05). Results indicate that small doses of IGF
      I, delivered in the form of liposomes, are equally effective in increasing burn
      wound reepithelialization as the higher doses of GH plus IGF-I, or GH plus IGF-I
      liposomes.

PMID- 9261693
TI  - Expression of cyclin protein after thermal skin injury in a guinea pig model.
AB  - In this study, an immunohistochemical stain for cyclin was used to quantitate
      proliferating elements in hair follicles at the edge of and within thermal burn
      areas. Biopsy specimens from thermal injury in the guinea pig (day 1 through day
      28) were sectioned and stained with MIB-1 antibody, which recognizes cyclin, a
      protein expressed during epithelial cell proliferation. At the edge of the burn,
      89 +/- 6.1 (SD) cells per medium power field (x 10, mpf) were MIB-1-positive on
      days 1 through 16. On day 17, the number of positive cells increased, reaching
      peak values on days 20 to 28 (271 +/- 12.7 cells/mpf). Within the burn, minimal
      staining was observed from day 1 to day 15 (12.7 +/- 1.6 cells/mpf). Thereafter
      the number of MIB-1-positive cells increased and plateaued with an average of
      96.4 +/- 9.0 cells/mpf on days 20 through 28. In conclusion, immunohistochemical
      staining of dermal biopsy specimens with MIB-1 antibody may provide a
      quantitative method for the evaluation of tissue damage and healing after thermal
      injury.

PMID- 9261695
TI  - A burn wound healing model in the hairless descendant of the Mexican hairless
      dog.
AB  - Wound contraction and epithelialization occur much faster in animals than in
      humans. Therefore it is sometimes not valid to apply the results of animal wound
      healing studies to humans. Hairless descendants of Mexican hairless dogs (HD-MHD)
      have attracted attention because their skin characteristics approximate those of
      humans. We used this animal and compared the rate of healing of superficial
      dermal burns (SDB) and deep dermal burns (DDB) in the HD-MHD and normal beagles.
      We also compared the rate of healing with use of Vaseline (Chesebrough-Ponds)
      gauze (VG) and hydrocolloid dressings in the HD-MHD. The HD-MHD demonstrated less
      contraction (p < 0.05). Small pigmented spots could be seen in the HD-MHD wounds,
      suggesting that epithelialization started from epidermal appendages. SDBs treated
      with VG and hydrocolloid dressings were both epithelialized on day 18. DDBs
      treated with hydrocolloid dressings were epithelialized on day 24, whereas DDBs
      treated with VG were epithelialized on day 30. Like human wounds, burns in the HD
      MHD epithelialize from appendages with less wound contraction. These similarities
      support the use of this burn wound healing model.

PMID- 9261696
TI  - Adjusting a prognostic score for burned children with logistic regression.
AB  - This study was aimed at the adjustment and cross-validation of a prognostic score
      for burned children on hospital admission. DEMI score assesses seven risk factors
      related to four main topics: depth (percent of partial-thickness and full
      thickness burn), extension (percent of total body surface area burned and injury
      to dorso-gluteal area), morbidity on admission (preexisting illness and
      complications caused by inadequate transfer), and presence of Inhalation
      syndrome. These items were selected in a previous case control study with
      bivariate analysis on an estimation sample of 168 children with acute burns
      admitted to the burn unit of the Hospital de Pediatria Juan P. Garrahan between
      July 1991 and October 1993. This study uses the same retrospective sample to
      adjust this score by means of multivariate analysis. Only four items were
      included in the logistic regression formula: percentage total body surface area
      burned, inadequate transfer, inhalation syndrome, and dorso-gluteal affection.
      Resulting abbreviation of DEMI score was then cross-validated on a prospective
      validation sample of 137 patients, yielding high correlation with the outcome (R
      = 0.78) and high sensitivity (80.95%), specificity (96.55%), and positive
      (80.95%) and negative (96.55%) predictive values. We conclude that this new DEMI
      score is a simple and accurate tool to predict mortality risk in burned children.

PMID- 9261694
TI  - Residual myocardial damage following electrical injuries.
AB  - It is unknown to what degree electrical injury causes cardiac muscle damage. We
      used standard clinical methods and varying combinations of 201Tl scintigraphy
      (TI), 123I-metaiodobenzylguanidine scintigraphy, echocardiography, 99mTc-RBC
      angiography, and coronary catheterization to evaluate five patients with high
      tension electrical injuries for cardiac damage. The first follow-up examination
      was performed within 2 months of injury, and the second follow-up was performed
      more than 6 months after the first follow-up. Electrocardiographic abnormalities
      were observed in two patients in the acute stage, but no abnormality was detected
      in the follow-up period. Myocardial perfusion abnormalities were found in all
      cases with Tl. The degree of injury indicated by Tl was more severe than that
      indicated by 123I-metaiodobenzylguanidine scintigraphy. Moreover, Tl showed
      progression of injury in all cases. These preliminary findings must now be
      confirmed and verified in a larger group of patients.

PMID- 9261697
TI  - Tunable dye laser neovessel ablation as an adjunct to the management of
      hypertrophic scarring in burned children: pilot trial to establish safety.
AB  - Hypertrophic scarring is a major source of morbidity in patients with burns. The
      physiologic characteristics are poorly understood, but increased neovascularity
      is typically seen in those wounds destined to become hypertrophic. We theorize
      that ablation of the developing neovasculature may favorably influence the
      development of the hypertrophic scar. The goal of this pilot trial was to
      establish the practicality and safety of tunable dye laser neovessel ablation at
      585 nm. Ten sites of evolving hypertrophic scar in nine children were treated
      with a series of 450 msec 6.75 J/cm2 pulses at 585 nm. Although all children had
      the expected transient posttreatment purpura, no pain, ulceration, pruritus, or
      worsening of the lesions was seen. The technique appears safe and is worthy of
      continuing investigation. Investigations with higher fluences and multiple
      treatments are in progress.

PMID- 9261698
TI  - Extensive burns caused by the abusive use of photosensitizing agents.
AB  - Psoralens are photosensitizing agents used in dermatology as reinforcements in
      psoralen ultraviolet A-range therapy. We report observations of 14 young women
      hospitalized for severe burns caused by abusive use of psoralens. The burns were
      of superficial and deep second-degree depth and covered more than 76% of the body
      surface on average. All patients needed fluid resuscitation. Hospital stay was 11
      days on average. Healing was obtained without skin grafting in all cases. Among
      the six patients who responded to the mailed questionnaire, negative effects are
      now present in all patients as inflammatory peaks. Two patients have esthetic
      sequelae such as dyschromia and scars. The misuse of photosensitizing agents
      poses many problems. These accidents are very expensive. The largeness of the
      burned surface can involve a fatal prognosis. And finally, one can suspect that a
      much larger portion of the population regularly uses these products without any
      serious accident. In this case carcinogenesis can be expected.

PMID- 9261699
TI  - Much ado about nothing: methicillin-resistant Staphylococcus aureus.
AB  - The pathogenic methicillin-resistant Staphylococcus aureus (MRSA) has received a
      voluminous amount of notoriety. The four major reasons are its morbidity,
      mortality rate, cost of treatment, and constant appearance in intensive care
      units. Both Staphylococcus aureus and S. epidermidis (MRSE) account for 82% of
      our gram-positive wound isolates, whereas the gram-negative account for 34% of
      all isolates. Therefore we compared the morbidity, mortality rate, and cost
      factors related to MRSA-MRSE and gram-negative infections for a 4-year period,
      assessing more than 214 documented infections. Morbidity and mortality rates were
      minor for MRSA. Pseudomonas aeruginosa and Escherichia coli accounted for 57.5%
      of the total gram-negative isolates. Gram-negative antimicrobial therapy usually
      requires two therapeutic drugs, which increases morbidity and costs, whereas the
      staphylococci usually can be treated by one antimicrobial. During this period
      there were 47 gram-negative infections requiring 10 to 15 additional days of
      hospital stay, with a daily antibiotic cost of $293.40. Costs for MRSA or MRSE
      are 28% less. Therefore our preoccupation with MRSA or MRSE infections is
      unwarranted and unsubstantiated.

PMID- 9261700
TI  - Distal-based flaps for reconstruction of hand burns.
AB  - Any burn injury, even if considered minimal in extent, can still be catastrophic,
      if hand burns are severe enough to result in deformities that render the
      individual unable to perform his own personal daily functions. Usually any
      necessary skin coverage of the hand can be achieved with skin grafts alone; but
      occasionally, seemingly heroic measures requiring vascularized flaps will be
      justified to ensure maximum rehabilitation. Previously, available options
      included proximal-based local flaps, or distant flaps either pedicled while
      remaining attached to another body region, or transferred immediately by use of
      microsurgical techniques. Another new concept that may still be somewhat in the
      investigational stage for burns is the distal-based local flap. These use more
      traditional proximal skin territories, but with a distal vascular pedicle that
      can allow such flaps to reach even the fingertips. More expeditious and
      technically simpler than the transfer of distant flaps, this alternative deserves
      further consideration in the appropriate circumstances.

PMID- 9261701
TI  - Allograft is superior to topical antimicrobial therapy in the treatment of
      partial-thickness scald burns in children.

PMID- 9261702
TI  - Study of antibiotic prophylaxis during burn wound debridement in children.
AB  - Twenty-three children completed a randomized, prospective, partially blinded
      study performed to assess the need and effectiveness of antibiotic prophylaxis at
      the time of burn wound debridement and grafting. Patients with a total body
      surface area (TBSA) burn less than 35% were randomized to receive cefazolin or
      placebo. Patients with burns of 35% or more TBSA were randomized to receive
      cefazolin or targeted antibiotics based on surveillance cultures. Blood cultures
      were obtained at commencement, immediately after, and 24 hours after surgical
      debridement. Quantitative cultures and histologic examination of biopsied burn
      wounds were performed. Burn wound infection occurred in three patients with burns
      of less than 35% TBSA, two in the cefazolin group and one in the placebo group.
      Quantitative tissue cultures and histologic examination did not predict either
      infection. During the four procedures in three patients with 35% or more TBSA,
      three were randomized to receive cefazolin, and one targeted antibiotics. All
      receiving cefazolin developed burn wound infection. Quantitative tissue culture
      was more than 10(5) colony-forming units per gram in all, whereas histologic
      examination was positive in one. In our patients with less than 35% burn,
      cefazolin was not necessary, and in those with 35% or more burn, it was not
      effective.

PMID- 9261703
TI  - Improved survival of adults with extensive burns.
AB  - Before 1988, survival of adults with burns > or = 75% total body surface area was
      uncommon in our burn unit. In 1988 a revised treatment plan for adult patients
      with burns > or = 75% was instituted. This plan included rapid disciplined eschar
      removal to fascia within 7 days, sequential meshed autografting with concomitant
      fresh allograft application, and early enteral feedings.

PMID- 9261704
TI  - Improved burn scar assessment with use of a new scar-rating scale.
AB  - The subjective assessment of scar appearance is a widely used method in the
      evaluation of burn outcomes and the efficacy of treatment methods. The purpose of
      this study is to design a numeric scar-rating scale with better interrater
      reliability than has previously been reported. The rating scale assesses scar
      surface, thickness, border height, and color differences between a scar and the
      adjacent normal skin. Eight raters were trained with use of a standardized set of
      photographs that provide examples of the scores to be assigned to each level of
      severity of each scar characteristic. The raters then rated 10 photographs of
      different scars, referring to the teaching set of pictures for comparison. The
      intraclass correlation (interrater reliability) was 0.94, 0.95, 0.90, and 0.85
      for scar surface, border height, thickness, and color, respectively. This rating
      system has proved to be a useful tool for the evaluation of scar surface,
      thickness, border height, and color.

PMID- 9261705
TI  - A burn center cost-reduction program.
AB  - A concerted effort to decrease resource usage and length of stay without
      sacrificing quality of care was undertaken over a 2-year period in a high-census
      Burn Center. Through a series of changes in practice, substantial decreases in
      the costs of several high-usage items were tracked. During this period the
      average length of stay also was decreased. The average hospital charge decreased
      from $46,628 per patient in fiscal year 1993 to $33,159 per patient in fiscal
      year 1994. During this period there was no significant change in the patient
      population as measured by total body surface area percentage burn and acuity
      level. With the exception of significant improvement in the infection rate, there
      was no substantial change in indicators of quality care as measured by
      readmission, morbidity, and posthospital would healing progression. This cost
      reduction program showed that costs can be reduced without diminishing quality of
      care; in some respects quality of care improved due to the practice changes that
      were implemented.

PMID- 9261706
TI  - Clinical nutrition protocols for continuous quality improvements in the outcomes
      of patients with burns.
AB  - Multiple guidelines for nutrition services in the postburn period exist. Given
      that nutrition intervention after burn injury affects outcome, it is appropriate
      to routinely consider methods for improving current practices. Effective
      nutrition therapies for the thermally injured individual are outlined in this
      article. Support for benchmarking these protocols is presented, and the
      completion of outcomes research in nutrition services for patients with burn
      injuries is encouraged.

PMID- 9261707
TI  - Childhood burns in camping and outdoor cooking accidents: a focus for prevention.
AB  - We have seen increasing numbers of children who present with serious burns
      related to camping and outdoor cooking, prompting this 5-year review. Of 34
      children (21 boys and 13 girls), with an average age of 5.2 years (4 months to 17
      years) and average burn size of 15% (1% to 98%) cared for (4 as outpatients and
      30 as inpatients), there was one fatality (3%). Mechanisms of injury included
      falling into free pits, throwing flammables into grills or pits, placing hands on
      hot objects in or near a fire, walking or falling into hot embers from an
      extinguished fire, spills from insect repellant candies, tent fires, burning of
      paper eating utensils, and cooking scalds. We have initiated a directed
      prevention program with the regional state park systems.

PMID- 9261708
TI  - Who chooses to undergo reconstructive surgery? Empirically confirming the
      subjectivity and social basis of body image.

PMID- 9261709
TI  - Psychologic factors involved in the decision to undergo reconstructive surgery
      after burn injury.
AB  - Burn injuries often result in permanent changes in physical appearance and
      function. Although reconstructive surgery is often considered to improve function
      or physical appearance, or a combination, variables that may predict use of
      surgery are relatively unknown. Burn survivors (N = 46; 48% male) were assessed
      at an evaluation for potential reconstructive surgery. Measures of adjustment,
      distress, and personality were administered. Several psychologic and demographic
      variables differed among those who did versus those who did not subsequently
      undergo surgery. Social, sexual, and family relationships were poorer among those
      who later used surgery, and surgery patients had higher scores on somatization.
      Subjects who had not returned to work, and individuals with private insurance or
      managed care, were significantly less likely to follow-up with reconstructive
      surgery. Contrary to hypothesized results, indexes of burn severity and the
      injury location were not significantly different between the two groups. Results
      suggest that interventions designed to aid adjustment after injury may result in
      the best surgical candidates completing reconstruction.

PMID- 9261710
TI  - The effects of isoproterenol on the cardiac conduction system: site-specific dose
      dependence.
AB  - INTRODUCTION: Isoproterenol is used to assess and facilitate AV nodal conduction,
      and thus potentiate the induction of supraventricular arrhythmias. It is commonly
      administered in increasing doses until a predetermined decrease in sinus cycle
      length, usually 20% to 30%, occurs. This regimen may result in undesirable side
      effects. We have observed that effects of isoproterenol on the AV node may occur
      prior to achieving the target sinus cycle length. The purpose of this study was
      to determine whether the sinus and AV nodes have equal sensitivity to
      isoproterenol. METHODS AND RESULTS: Thirty-eight consecutive patients, who
      underwent electrophysiologic evaluation for a variety of indications, were given
      incremental doses of isoproterenol at 0.007, 0.014, 0.021, and 0.028 microgram/kg
      per minute. Sinus cycle length and AV node function were assessed at baseline and
      after 5 minutes at each dose. The percent change from baseline in AV node
      function was compared with the change in sinus cycle length at each dose
      interval. Significantly greater decreases were observed in the anterograde and
      retrograde AV nodal Wenckebach cycle length (P < 0.0001) than in the sinus cycle
      length at the lowest isoproterenol dose (0.007 microgram/kg per min). These
      differences were not apparent at higher doses. A sustained supraventricular
      tachycardia was inducible in 15 of 38 patients in the presence of isoproterenol,
      of which 40% occurred at the lowest dose. CONCLUSIONS: The AV node is more
      sensitive than the sinus node to the effects of isoproterenol. Lower doses of
      isoproterenol than those commonly used may often facilitate the induction of a
      supraventricular tachyarrhythmia, thus reducing side effects.

PMID- 9261711
TI  - Adenosine-sensitive atrial reentrant tachycardia originating from the
      atrioventricular nodal transitional area.
AB  - INTRODUCTION: Atrial tachycardia shows wide variations in its electrophysiologic
      properties and sites of origin. We report an atrial tachycardia with ECG
      manifestations and electrophysiologic characteristics similar to an atypical form
      of AV nodal reentrant tachycardia (AVNRT). METHODS AND RESULTS: This
      supraventricular tachycardia was observed in 11 patients. It was initiated by
      atrial extrastimulation with an inverse relationship between the coupling
      interval of an extrastimulus and the postextrastimulus interval. Its induction
      was not related to a jump in the AH interval, and its perpetuation was
      independent of conduction block in AV node. Ventricular pacing during tachycardia
      demonstrated AV dissociation without affecting the atrial cycle length. A very
      small dose of adenosine triphosphate (mean 3.9 +/- 1.2 mg) could terminate the
      tachycardia. The earliest atrial activation during tachycardia was recorded at
      the low anteroseptal right atrium with a different intra-atrial activation
      sequence from that recorded during ventricular pacing, where the tachycardia was
      successfully ablated in 9 of 10 attempted patients. Bidirectional AV nodal
      conduction remained unaffected after successful ablation. CONCLUSION: There may
      be an entity of adenosine-sensitive atrial tachycardia probably due to focal
      reentry within the AV node or its transitional tissues without involvement of the
      AV nodal pathways. This tachycardia can be ablated without disturbing AV nodal
      conduction from the right atrial septum.

PMID- 9261712
TI  - Developmental changes in modulation of cardiac repolarization by sympathetic
      stimulation: the role of beta- and alpha-adrenergic receptors.
AB  - INTRODUCTION: Our goals were to study the role of development in determining the
      cardiac effects of sympathetic neural activation, and to identify the roles of
      alpha- and beta-adrenergic receptor-mediated pathways in modulating the effects
      of sympathetic stimulation. METHODS AND RESULTS: We compared responses of young
      and adult canine hearts in situ to right, left, and bilateral stellate ganglion
      stimulation. We focused on changes in heart rate, rhythm, QT interval, rate
      corrected QT interval (QTc), and T wave amplitude. Right stellate stimulation
      (RSS) induced more pronounced sinus tachycardia in adult than young animals. Left
      stellate stimulation (LSS) induced junctional tachycardia in adult more than
      young animals. In adults, LSS and RSS prolonged QTc (LSS > RSS), whereas 1-week
      olds manifested QTc shortening with RSS. LSS also increased T wave amplitude,
      most markedly in adults. In all studies, bilateral stellate stimulation induced
      responses intermediate between those seen with RSS and LSS. beta-Adrenergic
      blockade (propranolol) abolished all responses to LSS in adult hearts, but alpha
      blockade (prazosin) attenuated only the LSS-induced prolongation in QTc.
      CONCLUSION: In the postnatal modulation of cardiac rhythm, rate, and
      repolarization by the sympathetic nervous system, beta-adrenergic receptors play
      a major role at all ages, whereas alpha-adrenergic receptors play a lesser role,
      which is manifested only in adults. Moreover, expression of junctional
      tachycardias, which are beta-adrenergically modulated, is seen only in the
      adults.

PMID- 9261713
TI  - Decreased density of Ito in left ventricular myocytes from German shepherd dogs
      with inherited arrhythmias.
AB  - INTRODUCTION: A colony of inbred German shepherd dogs with inherited ventricular
      arrhythmias has been established. METHODS AND RESULTS: The inward rectifier
      (IK1), the slow delayed rectifier (IKs), and the transient outward current
      (I(to)) were recorded from epicardial myocytes, and Ito was recorded from
      Purkinje myocytes isolated from the left ventricles of dogs mildly or severely
      affected with arrhythmias, and unaffected relatives. There were no differences
      between unaffected and severely affected dogs in the densities of either IK1 or
      IKs. Peak Ito density at +40 mV was reduced by 49% in epicardial myocytes from
      severely affected dogs. I(to) density was also reduced in a subset of Purkinje
      myocytes. Boltzmann analysis of steady-state inactivation showed no differences
      between groups in slope factor. V1/2, the half-inactivation voltage, was shifted
      by +6.2 mV in epicardial cells from severely affected versus unaffected dogs. In
      addition, the time constant for I(to) decay was reduced in mildly and severely
      affected dogs compared to unaffected dogs. CONCLUSION: Altered density and
      inactivation of I(to) are associated with the presence of severe ventricular
      arrhythmias in inbred dogs at risk for sudden death.

PMID- 9261714
TI  - Cellular electrophysiology, heterogeneity, and arrhythmias.

PMID- 9261715
TI  - Abnormal action potential conduction in isolated human hypertrophied left
      ventricular myocardium.
AB  - INTRODUCTION: Cardiac hypertrophy is associated with an increased incidence of
      arrhythmias that result from altered action potential configuration or
      propagation velocity. These variables were measured in isolated preparations of
      human left ventricular myocardium and correlated with the degree of hypertrophy.
      METHODS AND RESULTS: Cardiac mass was estimated by echocardiography and cell
      diameter was measured from fixed isolated specimens; the two variables correlated
      significantly. Action potential duration was measured under field stimulation but
      was independent of the degree of hypertrophy; however, the duration was longer in
      septal preparations (405 +/- 12 msec, 37 degrees C, 1-Hz stimulation) than in
      papillary muscles (342 +/- 11 msec). Conduction velocity decreased progressively
      as cell diameter increased both in septal and papillary muscle preparations.
      Cable analysis showed that the variation of conduction velocity could be
      accounted for adequately by an increase of the intracellular resistivity of the
      preparations. CONCLUSION: The data suggest that conduction defects occur in a
      progressive manner in human hypertrophy, which would provide an important
      substrate for dysrhythmias in human left ventricular hypertrophy and could result
      from a decrease of electrical coupling between adjacent myocardial cells.

PMID- 9261716
TI  - The ventricular defibrillation and upper limit of vulnerability dose-response
      curves.
AB  - INTRODUCTION: A stimulus delivered in the T wave of a paced cardiac cycle can
      induce ventricular fibrillation (VF). If the stimulus strength is increased, the
      probability of inducing VF decreases. This study determines an ideal mathematical
      model (a dose-response curve) for the relationship between the shock strength and
      the probability of inducing VF or defibrillating. METHODS AND RESULTS:
      Defibrillating electrodes were implanted in the right ventricle and superior vena
      cava in 16 pigs. The electrode in the vena cava was electrically connected to a
      cutaneous patch. The same electrodes were used for both VF induction and
      defibrillation. T wave stimuli were given at the peak of the T wave according to
      a modified up-down protocol (40 V up, 20 V down). When a T wave stimulus induced
      VF, a defibrillation stimulus was delivered 10 seconds later, also according to
      the modified up-down protocol. Exponential, logistic, log-dose logistic,
      piecewise linear and Box-Tiao dose-response curves were fit to the resulting data
      using the maximum likelihood method. For the defibrillation data, it was found
      that only the logistic and Box-Tiao curves fit all of the animals (P < 0.05). For
      VF induction, only the Box-Tiao curve fit all of the animals (P < 0.05).
      Extrapolating along a dose-response curve that did not fit to a shock strength
      with a very low probability of inducing VF or a very high probability of
      defibrillating yielded errors as great as 610 V. CONCLUSION: The Box-Tiao dose
      response curve is the best single choice for fitting VF induction or
      defibrillation datasets.

PMID- 9261717
TI  - Electrophysiology of the atrio-AV nodal inputs and exits in the normal dog heart:
      radiofrequency ablation using an epicardial approach.
AB  - INTRODUCTION: We studied the effects of selective and combined ablation of the
      fast (FP) and slow pathway (SP) on AV and VA conduction in the normal dog heart
      using a novel epicardial ablation technique. METHODS AND RESULTS: For FP
      ablation, radiofrequency current (RFC) was applied to a catheter tip that was
      held epicardially against the base of the right atrial wall. SP ablation was
      performed epicardially at the crux the heart. Twenty-three dogs were assigned to
      two ablation protocols: FP/SP ablation group (n = 17) and SP/FP ablation group (n
      = 6). In 12 of 17 dogs, FP ablation prolonged the PR interval (97 +/- 10 to 149
      +/- 22 msec, P < 0.005) with no significant change in anterograde Wenckebach
      cycle length (WBCL). Subsequent SP ablation performed in 8 dogs further prolonged
      the PR interval and the anterograde WBCL (117 +/- 22 to 193 +/- 27, P < 0.005).
      Complete AV block was seen in 1 of 8 dogs, whereas complete or high-grade VA
      block was seen in 6 of 8 dogs. In the SP/FP ablation group, SP ablation
      significantly increased WBCL with no PR changes. Combined SP/FP ablation in 6
      dogs prolonged the PR interval significantly, but no instance of complete AV
      block was seen. VA block was found in 50% of these cases. Histologic studies
      revealed that RFC ablation affected the anterior and posterior atrium adjacent to
      the undamaged AV node and His bundle. CONCLUSION: Using an epicardial approach,
      combined ablation of the FP and SP AV nodal inputs can be achieved with an
      unexpectedly low incidence of complete AV block, although retrograde VA
      conduction was significantly compromised.

PMID- 9261718
TI  - Transcoronary venous radiofrequency catheter ablation of ventricular tachycardia.
AB  - Ventricular tachycardias in coronary artery disease arise mostly from endocardial
      sites. However, little is known about the site of origin in other diseases. We
      present the case of an incessant, adenosine-sensitive ventricular tachycardia
      arising from the lateral wall of the left ventricle in a patient with mildly
      reduced left ventricular function. Intracardiac mapping suggested an epicardial
      origin, and the tachycardia was successfully ablated from a coronary sinus
      branch. After ablation, left ventricular function returned to normal.
      Transcoronary venous radiofrequency catheter ablation is a new approach for the
      treatment of ventricular tachycardia. Its value in the management of other types
      of ventricular tachycardia has yet to be determined.

PMID- 9261719
TI  - Symptomatic atrioventricular block in an atriofascicular pathway inserting into
      the left bundle branch without apparent atrioventricular node function.
AB  - We report a patient with symptomatic AV block associated with conduction solely
      through an atriofascicular pathway that inserted into the left bundle branch.
      There was no apparent conduction present through the AV node. There was, however,
      passive activation through the His-Purkinje system. His-bundle pacing
      demonstrated normal conduction through both right and left bundles. This is the
      first report of such a case.

PMID- 9261720
TI  - The seventh annual Gordon K. Moe Lecture. Atrial fibrillation: from cell t
      bedside.
AB  - Atrial fibrillation is the most common sustained tachyarrhythmia and, as such,
      has become the recent focus of intense clinical and experimental interest.
      Because of its associated morbidity and mortality, there is a multidisciplinary
      effort to understand the pathophysiology that may ultimately lead to improved
      therapeutic options. This review concentrates on three aspects of atrial
      fibrillation that influence contemporary choices for treatment: an
      electrophysiologic basis for initiation of atrial fibrillation, anatomic and
      electrophysiologic remodeling, and concepts regarding its termination or
      prevention.

PMID- 9261721
TI  - Structure of connexin43 and its regulation by pHi.
AB  - Electrical coupling in the heart provides an effective mechanism for propagating
      the cardiac action potential efficiently throughout the entire heart. Cells
      within the heart are electrically coupled through specialized membrane channels
      called gap junctions. Studies have shown that gap junctions are dynamic,
      carefully regulated channels that are important for normal cardiogenesis. We have
      recently been interested in the molecular mechanisms by which intracellular
      acidification leads to gap junction channel closure. Previous results in this lab
      have shown that truncation of the carboxyl terminal (CT) of connexin43 (Cx43)
      does not interfere with functional channel expression. Further, the pH-dependent
      closure of Cx43 channels is significantly impaired by removal of this region of
      the protein. Other studies have shown that the CT is capable of interacting with
      its receptor even when not covalently attached to the channel protein. From these
      data we have proposed a particle-receptor model to explain the pH-dependent
      closure of Cx43 gap junction channels. Detailed analysis of the CT has revealed
      interesting new information regarding its possible structure. Here we review the
      most recent studies that have contributed to our understanding of the molecular
      mechanisms of regulation of the cardiac gap protein Cx43.

PMID- 9261722
TI  - Indications for radiofrequency ablation in the pediatric population.
AB  - Pediatric radiofrequency ablation procedures have become commonplace since their
      introduction to clinical practice 6 years ago. Excellent success rates coupled
      with low complication rates have allowed these procedures to be offered as first
      line therapy to many children. This review focuses on the current indications for
      radiofrequency ablation in children. These indications are not the same as for
      adults. They are based on the natural history of various forms of arrhythmias,
      the risks of the procedure, and the current success rates of the procedures, all
      of which are dependent upon the age of the patient.

PMID- 9261723
TI  - Cycle length and QRS alternation during a narrow QRS tachycardia.

PMID- 9261724
TI  - Computer model analysis of the relationship of ST-segment and ST-segment/heart
      rate slope response to the constituents of the ischemic injury source.
AB  - The objective of the study was to investigate a proposed linear relationship
      between the extent of myocardial ischemic injury and the ST-segment/heart rate
      (ST/HR) slope by computer simulation of the injury sources arising in exercise
      electrocardiographic (ECG) tests. The extent and location of the ischemic injury
      were simulated for both single- and multivessel coronary artery disease by use of
      an accurate source-volume conductor model which assumes a linear relationship
      between heart rate and extent of ischemia. The results indicated that in some
      cases the ST/HR slope in leads II, aVF, and especially V5 may be related to the
      extent of ischemia. However, the simulations demonstrated that neither the ST
      segment deviation nor the ST/HR slope was directly proportional to either the
      area of the ischemic boundary or the number of vessels occluded. Furthermore, in
      multivessel coronary artery disease, the temporal and spatial diversity of the
      generated multiple injury sources distorted the presumed linearity between ST
      segment deviation and heart rate. It was concluded that the ST/HR slope and ST
      segment deviation of the 12-lead ECG are not able to indicate extent of ischemic
      injury or number of vessels occluded.

PMID- 9261725
TI  - Continuous ST-segment monitoring during coronary angioplasty using orthogonal ECG
      leads.
AB  - In order to characterize ST-segment shifts during transient coronary artery
      occlusion, 24 patients with single-vessel disease were continuously monitored
      during percutaneous transluminal coronary angioplasty by use of a computerized
      orthogonal lead system. Changes of ST-segment (J + 60 ms) in leads X, Y, and Z
      and of the ST vector magnitude were analyzed by using 20 microV as a threshold
      for significant ST-segment shift. The sensitivity and magnitude of this shift
      were compared among the left anterior descending, right coronary, and circumflex
      artery groups (11, 8, and 5 patients, respectively) during balloon inflation.
      Significant ST-segment shifts were seen in 22 patients (92%) in ST-VM, Y, and Z
      leads and all patients in lead X (100%). There was no significant difference in
      sensitivity of either the ST vector magnitude or the most sensitive lead for
      occlusion detection among the three groups. There was a significantly greater
      magnitude of ST shift during left anterior descending artery occlusion than
      during right coronary artery and circumflex artery occlusions in ST-VM. Analysis
      of the direction of ST shifts in the X, Y, and Z leads showed a characteristic
      pattern, which could distinguish among the three coronary groups in 21 patients
      (88%). The presence of collaterals was significantly associated with ST-segment
      depression in leads oriented toward ischemia (3 of 6 patients) as compared with
      ST-segment elevation in the absence of collaterals (all of 15 patients), P > .01.
      It is concluded that ST-segment shift in the orthogonal leads is a reliable
      marker for myocardial ischemia. It is equally sensitive to occlusion of each of
      the three major coronary arteries and can thus identify the occluded coronary. An
      ST-segment depression instead of an elevation was related to the presence of
      collaterals, which may reflect a lesser degree of ischemia.

PMID- 9261726
TI  - Comparison of dobutamine ECG stress test with predischarge exercise test after
      acute myocardial infarction.
AB  - Exercise testing after acute myocardial infarction is commonly used, but in
      recent years alternative methods have been proposed. Standard exercise testing
      was compared with dobutamine electrocardiographic (ECG) stress testing in 100
      patients after an acute initial myocardial infarction. Dobutamine ECG stress
      testing was performed in a standard manner at 5 +/- 1 days after the infarction
      and exercise testing was performed a mean of 10 +/- 2 days following the event.
      Agreement between both tests was observed in 91 cases (91%), P < .001, Fisher
      test kappa value, 0.79). The dobutamine test predicted the result of the exercise
      test with a sensitivity of 100% (95% confidence interval, 87-100) and a
      specificity of 88% (95% confidence interval 77-93) for a positive predictive
      value of 75% (95% confidence interval, 62-97) and a negative predictive value of
      100% (95% confidence interval, 91-100). Dobutamine ECG stress testing is
      concluded to be an objective and reliable procedure, which accurately predicts
      the results of standard exercise testing. It is inexpensive, easy to perform, and
      although not yet confirmed, could be particularly useful in patients who cannot
      perform exercise.

PMID- 9261727
TI  - Assessment of ischemic changes by ambulatory ECG-monitoring: comparison with 12
      lead ECG during exercise testing.
AB  - The accuracy of commercially available ambulatory electrocardiographic monitoring
      (AEM) systems for reproducing ischemic changes has been questioned. Since these
      systems are widely used for evaluation of ST-segment changes, both for prognostic
      purposes and for assessment of the efficacy of antiischemic drugs, such doubts
      must be clarified. For this purpose, we recorded electrocardiograms (ECGs) during
      exercise testing, using split leads, simultaneously with a 12-lead
      electrocardiograph and with the Marquette AEM recorder. We studied 29 patients
      with proven coronary artery disease and positive exercise tests and 19
      individuals with low likelihood of coronary artery disease and negative stress
      tests. All 29 patients who had ST-segment depression during exercise as recorded
      on the 12-lead ECG had ST-segment depression in at least one of the three AEM
      leads (resembling the V5, V3, and aVF leads of the 12-lead system). The maximal
      degree of ST-segment depression with AEM was similar to 12-lead ECG (2.3 mm and
      2.1 mm, respectively). The best lead for ischemia detection with AEM was the V5
      type, which detected ischemic changes in 26 of the 29 patients, while the 12-lead
      V5 detected ischemia in 24 patients. The inferior AEM lead detected ischemia in
      only 4 patients, while the aVF lead of the 12-lead ECG detected ischemia in 23
      patients. Of the 19 patients with negative exercise tests only 1 patient had a 1
      mm ST-segment depression on AEM. Thus, of the 48 patients studied, similar
      responses were observed in 47. The results of indicate that the Marquette AEM
      system is as accurate as the 12-lead ECG in detecting ischemic changes and in
      assessing their severity.

PMID- 9261728
TI  - Circadian variation of QT interval dispersion: correlation with heart rate
      variability.
AB  - The circadian variation of QT interval dispersion and its correlation with heart
      rate variability (HRV) was examined in 17 normal subjects by using 24-hour
      recordings of three-lead electrocardiograms. Measurements of HRV, R-R intervals,
      and QT intervals were made for the first 6 minutes of each hour over a 24-hour
      period. Spectral analysis of HRV yielded low-frequency power (LF) (0.04-0.15 Hz),
      high-frequency power (HF) (0.15-0.40 Hz), and the ratio of LF to HF (LF/HF). A
      rate-corrected QT interval (QTc) was calculated by Bazett's formula, and QT and
      QTc dispersion was defined as the difference between the maximum and minimum
      values in any two leads. High-frequency power and QT interval were greater at
      night than during the day: conversely, LF/HF and dispersion of QT and QTc were
      greater during the day. The QTc interval remained virtually unchanged throughout
      the 24-hour period. The dispersion of QTc showed a significant negative
      correlation with HF and a significant positive correlation with LF/HF. The
      results suggest that an increased sympathetic tone or a decreased vagal tone
      increases QT dispersion in healthy subjects.

PMID- 9261729
TI  - Changes in R wave amplitude: ECG differentiation between episodes of reocclusion
      and reperfusion associated with ST-segment elevation.
AB  - This study assesses the electrocardiographic (ECG) differences between episodes
      of increased ST-segment amplitude induced by coronary artery occlusion and by
      reperfusion in the open-chest rabbit model. Nine anesthetized open-chest male New
      Zealand White rabbits were subjected to four episodes of 5 minutes of coronary
      artery occlusion followed by 5 minutes of reperfusion. The ST-segment and R wave
      amplitudes were measured from an ECG lead attached to the pericardium overlying
      the ischemic myocardium. In 10 out of 35 (29%) of the episodes, reperfusion
      resulted in a transient increase in ST-segment amplitude. While episodes of
      coronary artery occlusion were associated with increase in R wave amplitude (69%
      and 97% of the episodes after 1 and 5 minutes, respectively), all reperfusion
      episodes were associated with prompt decrease in R wave amplitude. There was no
      difference between the repeated episodes in the occurrence of ST-segment
      elevation during reperfusion. However, ST-segment elevation during reperfusion
      could be distinguished from the ischemic episodes by the prompt decline in the R
      wave amplitude in the former compared with no change or increase in the latter.

PMID- 9261730
TI  - Facilitation of epinephrine-induced afterdepolarizations by class III
      antiarrhythmic drugs.
AB  - The electrophysiologic actions of epinephrine (10(-9) M, 10(-8) M, and 10(-7) M)
      were evaluated in canine Purkinje fibers pretreated with the class III
      antiarrhythmic drugs clofilium (10(-7) M) or d,l-sotalol (10(-6) M). Clofilium
      and d,l-sotalol prolonged action potential duration at 50% and 90% of
      repolarization without provoking early afterdepolarization (EAD) or delayed
      afterdepolarization (DAD). Subsequent administration of epinephrine provoked both
      bradycardia-dependent EADs and tachycardia-dependent DADs in clofilium-treated
      Purkinje fibers, with predominantly EADs observed in d,l-sotalol-treated Purkinje
      fibers. A temporary increase in Ca0(+2) from 1.35 mM to 5 mM suppressed both EADs
      and DADs. The data demonstrate facilitation of epinephrine-induced EADs and DADs
      by class III antiarrhythmic drugs. The acute suppression of both EADs and DADs
      observed following an acute increase in Ca0(+2) suggests inward Na(+)-Ca0(+2)
      exchange current as a basis for both EADs and DADs observed in the presence of
      class III antiarrhythmic drugs and epinephrine.

PMID- 9261731
TI  - Spectral analysis of electrograms during ventricular tachycardia in a canine
      model: relation with epicardial isochronal maps.
AB  - The purpose of this study was to assess the capability of magnitude-squared
      coherence and bicoherence to differentiate monomorphic ventricular tachycardia
      (MVT) and polymorphic ventricular tachycardia (PVT) in a canine model and to
      relate these results to the epicardial isochronal maps on a beat-to-beat basis.
      Unipolar electrograms were simultaneously recorded from the surface of both
      ventricles with a 127-lead sock electrode array in 12 open-chest anesthetized
      dogs. The sampling frequency was 500 Hz. Atrioventricular block was induced by
      formaldehyde injection into the atrioventricular node. The left anterior
      descending coronary artery was occluded for 60 minutes under ventricular pacing
      (140 beats/min). During reperfusion, 12 MVT episodes lasting more than 42 seconds
      were recorded. Left stellate ganglion stimulation induced five PVT episodes
      lasting more than 42 seconds. Each of these recordings was divided into seven
      segments of 3,072 points (6.144 seconds). After visual selection, 104 segments
      were extracted and classified as 73 MVT and 31 PVT segments. Magnitude-squared
      coherence was estimated as the cross-spectrum from two epicardial signals (on the
      right and left ventricles, respectively), normalized with the respective
      autopower spectrum. Bicoherence was estimated as the bispectrum normalized with
      the autopower spectrum. Magnitude-squared coherence correctly identified 96% of
      MVT and 81% of PVT segments for a total accuracy of 91%. Bicoherence estimated
      with the left ventricular lead correctly identified 100% of MVT and 77% of PVT
      segments with an accuracy of 93%. Beat-to-beat epicardial maps of MVT displayed a
      cluster of sites of origin close to the reperfusion area, while the sites of
      origin from beats during PVT were much more dispersed over both ventricles. A
      strong and significant correlation was found between the number of electrodes
      with the earliest epicardial activation and coherence (r = .76, P < .0001) and
      bicoherence (r = .68, P < .0001), respectively. A high and significant
      correlation was also found between both spectral estimators (r = .74, P < .0001).
      Coherence and bicoherence discriminated accurately between MVT and PVT. Coherence
      achieved better results compared with bicoherence. Coherence and bicoherence
      measurements showed a quantitative relation with the spatial dispersion of the
      sites of origin. Both spectral techniques seemed powerful enough to be used in
      the development of implantable devices.

PMID- 9261732
TI  - Increase in heart rate after radiofrequency catheter ablation is mediated by
      parasympathetic nervous withdrawal and related to site of ablation.
AB  - To assess the mechanism for the increased sinus rate after radiofrequency
      catheter ablation performed for atrioventricular nodal reentrant tachycardia
      (AVNRT), we studied heart rate variability before and after radiofrequency
      catheter ablation in 17 patients with AVNRT and in 38 patients with an accessory
      pathway. The accessory pathway was located at the left ventricular free wall, the
      right ventricular free wall, or the posterior interventricular septum. An
      increased sinus rate was observed in patients with AVNRT or with the accessory
      pathway at the posterior septum or left free wall after radiofrequency ablation.
      In these groups, high-frequency power, root mean square of successive difference
      and percent of adjacent cycles that were more than 50 ms apart, all of which are
      indices reflecting parasympathetic nervous activity, were decreased. The ratio of
      low-frequency to high-frequency power reflecting sympathovagal balance, was
      increased in patients with AVNRT or with an accessory pathway at the posterior
      septum or left free wall. Increases in sinus rate were correlated with decreases
      in high-frequency power, and percent of adjacent cycles more than 50 ms apart
      that the increase in heart rate was due to parasympathetic nervous withdrawal.

PMID- 9261733
TI  - Effect of electrode positioning on ECG interpretation by computer.
AB  - The aim of this study was to assess the variability in automated
      electrocardiogram (ECG) interpretation due to electrode positioning variations.
      Such variations were simulated by using a set of 746 body surface potential
      mappings from apparently healthy individuals and patients with myocardial
      infarction or left ventricular hypertrophy. Four types of electrode position
      changes were simulated, and the effect on ECG measurements and diagnostic
      classifications was determined by a computer program. At most 6% of the cases
      showed important changes in classification for longitudinal shifts. Transversal
      shifts causes less than 1.5% of important changes. An expert cardiologist, who
      analyzed a subset of 80 cases, agreed with the computer in 38 of 40 cases in
      which it made no change. In the 40 cases with large diagnostic changes, the
      cardiologist made no change in 18 cases. The effect of electrode position changes
      on ECG classification by an expert cardiologist was about half of the effect
      determined by computerized ECG classification. The effects on classification are
      significant; therefore, correct placement of chest electrodes remains mandatory.

PMID- 9261734
TI  - Precordial leads QRST time integrals for evaluation of right ventricular overload
      in children with congenital heart diseases.
AB  - It was previously shown that body surface QRST isointegral maps of the anterior
      chest were abnormal in patients with right ventricular overload and that the
      abnormalities varied with hemodynamic status. The QRST isointegral maps were
      first characterized by using a departure index map for normal controls. The study
      group consisted of 14 patients with pulmonary stenosis (PS), 20 with tetralogy of
      Fallot, (TOF) and 43 with atrial septal defect (ASD). The QRST isointegral maps
      of these three groups were compared with the data on 23 to 65 age-matched normal
      children. In mean departure index maps, the patients with right ventricular
      pressure overload (PS or TOF) showed an increase in departure index on the
      anterior midchest, while those of right ventricular volume overload (ASD) showed
      two maxima on the anterior and left lateral chest, with a trough-like negative
      area between them. Since the abnormal findings were seen on the anterior chest,
      we evaluated the diagnostic usefulness of QRST time integral values for
      precordial leads of the routine electrocardiogram (ECG) in a second part of this
      study. The precordial QRST time integral values from 9 patients with PS and 11
      with TOF (0-2 years of age, mean 1.1 years) and 22 ASD patients (6-15 years, mean
      10.1 years) were compared with those of the age-matched control children. The
      QRST time integral values of the precordial leads in right ventricular pressure
      overload were significantly increased in the right precordial leads (V1, V2). In
      right ventricular volume overload, the QRST time integral values of the V1, V2,
      V4, and V6 leads demonstrated a significant deviation from those of the control
      group. Therefore, a discrimination formula was constructed by using the values of
      these leads, and the criteria derived from this formula revealed good (98%)
      diagnostic accuracy. In detection of right ventricular overload, the QRST time
      integral values of the precordial lead ECG, if confirmed in a larger data set,
      may be useful as a simple screening method.

PMID- 9261735
TI  - Case report of a hypermobile pacemaker: abnormal manifestations and surgical
      correction.
AB  - An abnormally mobile subclavian pacemaker pulse generator in a 49-year-old woman
      was stabilized by an absorbable mesh graft. This device was successfully replaced
      2 years later without any problems. A 4-year follow-up evaluation was uneventful.

PMID- 9261736
TI  - Expression of epidermal growth factor in gestational trophoblastic disease (GTD).
AB  - Gestational Trophoblastic Disease (GTD) is an abnormal condition of the placenta,
      the incidence of which is very high in the State of Kerala, India. The biology of
      the disease is vague and methods to determine the malignant potentialis limited.
      Placentae of normal (50) and molar pregnancy (95) including 32 patients showing
      persistent disease were used in this study. EGF expression was analyzed by
      immunohistochemistry using monoclonal antibody to EGF and quantitated using
      isotope labelled antibody to EGF. EGF was expressed more strongly in molar
      placentae in all gestational ages in comparison with normal placentae of similar
      gestational age, the expression being restricted mainly to first and second
      trimesters in normal placentae. Moles with early presenting symptoms (< 12 weeks)
      were at a higher risk for developing persistent disease. In conclusion, the
      immunohistochemical study shows high expression of EGF in early normal placentae
      and moles linking its role to proliferative and differentiating activity of
      trophoblasts. Tumors with histological diagnosis of invasive moles and
      choriocarcinoma showed very strong binding of EGF and thus EGF has the potential
      of identifying high risk lesions.

PMID- 9261737
TI  - Effects of dibutyryl cyclic adenosine monophosphate on nucleolar organizer
      regions and epidermal growth factor receptor of Dunn osteosarcoma cells.
AB  - We investigated the characteristics of nucleolar organizer regions (NORs) and
      epidermal growth factor receptor (EGFR) on differentiated Dunn osteosarcoma in
      response to dibutyryl cyclic adenosine 3',5'-monophosphate (Bt2cAMP). In the
      presence of 3 mM Bt2cAMP, the mean number of NORs was significantly decreased in
      24 hrs and 48 hrs compared with the untreated group. Also, EGFR affinity was
      decreased and the EGFR number was increased in response to the cellular
      differentiation by Bt2cAMP. The decrease in EGFR affinity might be considered as
      an indicator of differentiation or the mature state of the cells. Thus, the
      present study provides a new clue to support differentiation of osteosarcoma
      cells from the viewpoint of NORs findings and EGFR analysis as a differentiation
      marker.

PMID- 9261738
TI  - The overexpression of p53 and proliferative activity in precancerous and
      cancerous lesions of oral squamous epithelium.
AB  - To understand the timing of p53 overexpression in oral carcinogenesis, we
      performed immunohistochemistry for p53 on 118 biopsy specimens containing various
      oral precancerous and cancerous lesions. The immunoreactivity for p53 protein was
      found in the nuclei of the parabasal layer in hyperplastic and precancerous
      lesions which increased according to the degree of dysplastic change. The
      overexpression of p53 protein reached the maximal frequency of 76% in squamous
      cell carcinoma. Moreover, proliferative activity was also evaluated by means of
      Ki-67 immunohistochemistry and the histochemical count of argyrophilic nucleolar
      organizer regions (AgNORs). Although these proliferation markers tended to
      increase in number according to the severity of oral lesions, they were weakly
      correlated with the results of p53 immunohistochemistry. Our results indicate
      that p53 overexpression is an early event in oral carcinogenesis never
      influencing the proliferative advantage in oral precancerous lesions.

PMID- 9261739
TI  - The effects of combined treatments with low hyperthermia and bleomycin on
      survivals of murine L cells.
AB  - Modification effects of low hyperthermia (40 degrees C) on cellular
      chemosensitivity to bleomycin (BLM), and of BLM on thermosensitivity (40 degrees
      C) were investigated in cultured murine L cells with simultaneous or sequential
      treatments of these two agents. The heating of L cells at 40 degrees C up to 6
      hours resulted in no remarkable lethal damage. Treatment with low hyperthermia
      followed by BLM for 4 hours showed no more than additive effect. However, a
      significant chemical (BLM) enhancement effect on the cellular thermosensitivity
      was observed by the treatment with BLM for 4 hours prior to the low hyperthermia
      at 40 degrees C. No appreciable thermal enhancement effect on the cellular
      chemosensitivity to BLM was shown by preheating at 40 degrees C for 3 hours,
      while post-heating at 40 degrees C showed a significant thermal enhancement
      effect as well as in the simultaneous treatments. The cell phase response to BLM
      was levelled in the clinical range of the doses. It is possible that the repair
      of sublethal damage (SLDR) from treatment with BLM was inhibited by 40 degrees C
      post-heating and this SLDR was completed at 3 hours of the interval at 37 degrees
      C between BLM and 40 degrees C heating.

PMID- 9261740
TI  - Proliferative potentials of glioma cells and vascular components determined with
      monoclonal antibody MIB-1.
AB  - Proliferative activity in 78 glioma specimens was assessed immunohistochemically
      by determining proliferating index of tumor cells (PTC-PI) and endothelial cells
      (PEC-PI) using the MIB-1 monoclonal antibody. The PTC-PI of anaplastic
      astrocytoma (9.0 +/- 5.8: mean + standard deviation) was significantly higher
      than that of astrocytoma (1.2 +/- 0.4, < 0.01), and lower than that of
      glioblastoma multiforme (12.0 +/- 5.6, < 0.05). We then compared PTC-PI values
      with the prognosis of patients with malignant glioma (both glioblastoma and
      anaplastic astrocytoma). Kaplan-Meier survival rate analysis demonstrated higher
      survival rates in patients with less than 8.0% of PTC-PI at 5 and 10 years (p <
      0.05). These results suggested PTC-PI provides useful information which may allow
      better assessment of the biological behaviour and clinical prognosis of glioma,
      in addition to histological grading. While the average PEC-PI value (3.3) was
      lower than that of PTC-PI (7.0), there was a significantly close relationship
      between them (p < 0.01), fostering the developments novel therapies directed
      towards suppression of microvascular regeneration.

PMID- 9261741
TI  - Effect of viscum album in the inhibition of lung metastasis in mice induced by
      B16F10 melanoma cells.
AB  - Effect of Iscador, an extract from semiparasitic plant Viscum Album on the
      inhibition of lung metastatic colony formation induced by B16F10 melanoma cells
      was studied in mice. Simultaneous administration of drug (1.66 mg/dose) and
      B16F10 melanoma cells could inhibit lung nodule formation by 92%. Prophylactic
      drug administration produced and inhibition of 78.6% and drug administration five
      days after tumour induction produced 68.16% inhibition of lung nodule formation.
      Lung hydroxyproline and serum sialic acid levels were also lower in the tumour
      bearing animals treated with Viscum Album. The animals treated with simultaneous
      drug administration had an increase of 71.34% in their life span.

PMID- 9261742
TI  - Responsiveness to recombinant human erythropoietin (rh-Epo) of marrow erythroid
      progenitors (CFU-E and BFU-E) from B-chronic lymphocytic leukemia (B-CLL).
AB  - The responsiveness of bone marrow erythroid progenitors (CFU-E and BFU-E) to
      various concentrations of recombinant human erythropoietin (rh-Epo)
      (2,5,20,40,100,200 and 500 U/ml) was investigated in vitro in 18 patients with B
      chronic lymphocytic leukemia to assess the clinical usefulness of rh-Epo in this
      disease. Bone marrow mononuclear cells were cultured by methylcellulose methods
      for CFU-E and BFU-E assays. The B-chronic lymphocytic leukemia patients were
      divided into two groups according to the percentage of lymphocytes in the bone
      marrow (under 70% and over 70%). Among the patients with few lymphocytes, more
      than one third demonstrated some degree of response to rh-Epo. Among the patients
      with a high percentage of lymphocytes in the bone marrow, some revealed no
      response to rh-Epo, but there were patients who showed a good response to rh-Epo.
      Because erythroid progenitors from B-chronic lymphocytic leukemia appeared
      sensitive to rh-Epo in vitro, we propose that high doses of this drug may be
      clinically effective in some patients with this disease, regardless of the degree
      of lymphocytic inflitration of the bone marrow.

PMID- 9261743
TI  - The heterogeneous expression of CD80, CD86 and other adhesion molecules on
      leukemia and lymphoma cells and their induction by interferon.
AB  - CD80 (B7/BB-1, B7-1) and CD86 (B70, B7-2) take an important role in the
      interaction between T lymphocytes and antigen presenting cells (APCs) as co
      stimulatory molecules. We analyzed the manifestation of adhesion molecules,
      including CD80 and CD86, on some leukemia and lymphoma cells. Constitutive
      expression of CD80 and/or CD86 was frequently observed on B cell
      leukemia/lymphoma cells, while it is rare on myeloid leukemia cells. Interferon
      alpha (IFN-alpha) amplified the manifestation of MHC class I and interferon-gamma
      (IFN-gamma) did both class I and class II. We also showed CD80 could be induced
      by IFN-alpha on K562 cells, which were originally negative for CD80. Our data
      implies the immunotherapy via CD80 and CD86 for patients with hematological
      malignancies and the possibility to enhance it using interferons.

PMID- 9261745
TI  - Leukopenia prognosis by radiation therapy of patients with Hodgkin's disease.
AB  - The investigation goal of the present study is the possible utilization of early
      postradiation peripheral blood DNA content changes during radiotherapy (RT) of
      cancer patients for prognostic purposes related to the subsequent ascertaiment of
      leukopenia values. Twenty-three primary patients with II-III stage Hodgkin's
      disease were treated at the linear accelerator of 15 Mev electrons by usual
      fractionation to a total dose of 40 Gy. The blood DNA content was
      fluorometrically determined by 4',6-diamidino-2-phenylindole before treatment, 24
      hrs after the first irradiated dose, in the middle and at the end of RT course.
      Retrospective analysis of obtained data demonstrated that the first patients'
      group with blood leukocyte level above 3 x 10(9) cells/l at the end of RT,
      revealed an average blood DNA concentration decrease only after half of the
      treatment course. The second group of patients, complaining at the end of RT
      severe leukopenia, showed a two-fold decrease of the DNA concentration after the
      first irradiation in 62% of cases. The biochemical changes were not accompanied
      by a proportional decrease of the leukocytes number. The early decrease of DNA
      content drop, at the middle and the end of RT course, was conditioned both by
      lymphocytes and granulocytes. These changes were not practically interfaced with
      plasma changes. Thus, given biochemical criteria may be used as a sensitive index
      for the prognosis of leukopenia values after the RT beginning. As confirmed by
      test-irradiation in vitro of blood specimens of primary patients with Hodgkin's
      disease. There was a significant correlation between the new index and the level
      of leukopenia during post-treatment course.

PMID- 9261744
TI  - HLA class II expression in well differentiated thyroid carcinoma: correlation
      with clinicopathological features.
AB  - Lymphocytic infiltration and aberrant expression of HLA class II antigens on
      malignant thyroid epithelial cells are assumed to play a relevant role in the
      immune response against thyroid cancer. Aberrant expression of the HLA class II
      alpha and beta chains as well as number and distribution of tumor infiltrating
      lymphocytes were investigated in primary tumors (n = 54) and metastases (n = 4)
      of well differentiated thyroid carcinomas (follicular carcinoma: n = 26,
      papillary carcinoma: n = 28). The immunohistochemical findings were correlated
      with clinicopathological features. An aberrant HLA class II beta chain expression
      was detected in 9 (28%) papillary carcinomas and 4 (15%) follicular carcinomas.
      Three HLA class II beta chain positive papillary carcinomas and all follicular
      carcinomas were negative for the HLA class II alpha chain. All lymph node and
      distant metastases were negative for both HLA class II alpha and beta chain.
      Number and distribution of CD45R0+ lymphocytes significantly (p < 0.05, Fisher
      test) correlated with the aberrant HLA II antigen expression on tumor cells.
      There was also a significant correlation (p < 0.05, Fisher test) between an
      aberrant HLA II antigen expression and invasion of the vessels. No correlation
      was found between aberrant HLA class II expression and the occurrence of lymph
      nodes or distant metastases. Our findings indicate that the expression of HLA
      class II antigens on thyroid carcinoma cells is high in the step of invasive
      growth and that the local immune response towards the HLA class II antigens
      appears to prevent metastatic spread of HLA II positive tumor cells. There is
      evidence of different expression of HLA class II chains in follicular and in
      papillary thyroid carcinomas, which could be a further indicator that in these
      two subgroups of thyroid carcinomas different changes in the regulatory
      mechanisms of HLA class II antigen expression occur.

PMID- 9261746
TI  - Intestinal type: diffuse type ratio of gastric carcinoma in a Mexican population.
AB  - This study was performed in order to define the histological patterns of gastric
      carcinoma according to Lauren's classification and the IT:DT ratio in a Mexican
      population. We analyzed the relative frequency of intestinal-type and diffuse
      type carcinomas in a group of patients, diagnosed at the Instituto Nacional de
      Cancerologia in Mexico City between 1982 and 1992. Of the 460 cases of gastric
      cancer, 242 (52.7%) were of the intestinal-type, 206 (44.7%) of the diffuse type,
      and 12 (2.6%) others. A predominance of the diffuse type among the younger age
      groups (< 50 years) was observed-the transitional age for men and women occurred
      in the sixth decade. The global intestinal: diffuse ratio was 1.2 and increased
      with age. This ratio remained similar during the 11 years of the analysis. Men
      had a higher proportion of intestinal type carcinoma than women. These findings
      indicate that Mexico is not a low risk area for gastric cancer with a
      consistently low intestinal: diffuse type ratio. Despite differences in
      geographic and demographic patterns, the intestinal and diffuse types of gastric
      carcinoma have common etiological factors.

PMID- 9261747
TI  - Postoperative combined radiohyperthermia in Astler-Coller stages B2 and C distal
      rectal cancer.
AB  - Pelvic perineal recurrence rate is the major therapeutic problem after curative
      surgery of extraperithoneal rectal cancer, after lower anterior resection as well
      as abdomino-perineal resection: local failure rate is high, particularly for
      stages B2-C. Radiotherapy alone or in combination with chemotherapy proved to be
      an useful adjunct to surgery. Postoperative radiotherapy, with 40 to 50 Gy doses,
      has shown local improvement, but causing intestinal damaging. There is now
      evidence that hyperthermia enthances radiation effects, by killing radioresistant
      acid tumor cells. In order to give high postoperative radiation doses, without
      intestinal damage, and to kill acid tumor cells by hyperthermia, we developed a
      device, able both to displace intestinal loops and to produce combined
      hyperthermia. From 1993 to 1995, four patients with Astler-Coller stages B2 (2
      patients), C1 (1 patient) and C2 (1 patient) distal cancer, were operated by
      Hartmann's procedure and treated with postoperative radio-hyperthermia with our
      device. Overall radiation dose delivered in the pelvic area was of 65 Gy,
      associated with three heating sessions at 43 degrees C for 30 minutes. Pelvic
      infection occurred in one patient; all pelvic byopsies were negative and no bowel
      damage was found. Three patients underwent recanalization, one had anasthomotic
      leackage. The C1 and C2 stage patients died from hepatic metastasis, 18 and 11
      months after recanalization; one B2 stage patient is still under treatment and
      the other is alive and disease free 13 months after recanalization. Our technique
      allows to give high postoperative radiation doses, without small intestine
      damage, and to give a good hyperthermia for better control of local failure.

PMID- 9261749
TI  - Depression secondary to tumors in patients who underwent surgery for mammary
      carcinoma: psycho-pharmaceutical and psychotherapeutic care.
AB  - The Authors repeated a pilot psycho-social research they had already undertaken
      in this University in 1986-1987, with an increased number of patients,
      administering a psycho-therapeutic treatment to patients who had undergone
      surgery for mammary carcinoma and correlating the evolution of the tumoral
      disease with the role of depression and the immune system. These 50 patients were
      compared to another randomly chosen control-group of 50 patients. Both groups
      were homogeneous as regards medical-surgical and psycho-social parameters and had
      routine oncological care. Only the patients of the study-group were submitted to
      individual psychotherapy and treated psychopharmacologically. At the end of the
      study, the two groups showed a statistically significant difference as regards
      the evolution of the tumoral disease in favour of the study-group. In addition, a
      relevant improvement from depression was recorded in the study-group along with a
      normalization and a boost of the immunological measurements.

PMID- 9261748
TI  - BOLD+interferon in the treatment of metastatic uveal melanoma: first report of
      active systemic therapy.
AB  - We conducted a phase II trial of bleomycin+vincristine+lomustine+dacarbazine
      (BOLD) with intercycle alpha interferon-2b in previously untreated patients with
      metastatic uveal melanoma. Objective tumor response and toxicity were assessed.
      Twenty-three patients with histologically verified metastatic uveal melanoma were
      enrolled into this study between November 1992 and August 1995. Chemotherapy was
      administered in the following fashion: dacarbazine (DTIC), 200 mg/m2
      intravenously on days 1-5; vincristine, 1 mg/m2 (not to exceed 2 mg)
      intravenously on days 1 and 4; bleomycin, 15 mg intravenously on days 2 and 5;
      lomustine (CCNU), 80 mg orally on day 1; and alpha interferon-2b, 3 x 10(6) IU
      subcutaneously on days 8, 10, 12, 15, 17, 19. A cycle was 28 days, and patients
      were reevaluated after every 2 cycles. Among twenty evaluable patients, four
      objective responses were observed (RR = 20%). Hematologic toxicity was modest by
      comparison to some other combination chemotherapy regimens in common use.
      Neurotoxicity was frequently observed, but it was seldom severe. An unexpected
      and unpredictable severe pulmonary toxicity was observed in 3 patients, the
      etiology of which remains unclear. The regimen of BOLD+interferon is active in
      the treatment of metastatic uveal melanoma. The precise role of the regimen has
      to be defined in light of its toxicity, particularly the unpredictable pulmonary
      toxicity. The pattern of occurrence of these pulmonary events is most consistent
      with either an acquired hypersensitivity reaction or a cumulative toxic effect of
      2 or more of the agents. Patients considered for treatment with this regimen must
      be judiciously selected. Those with no clear contraindications may benefit from a
      trial of this regimen, but they must be monitored closely.

PMID- 9261750
TI  - How to decrease false-positive cases of ovarian cancer screening by transvaginal
      sonography.
AB  - Screening for ovarian cancer is an important step in improving ovarian cancer
      mortality. This is a report of screening for ovarian cancer using transvaginal
      sonography (TVS) on 2,095 asymptomatic women during the past four years. Ovarian
      tumors over 30 mm in diameter were detected in 87 women (4.2%). Fourteen tumors
      were morphologically classified as complex type and 73 as cystic type. Only 12
      tumors were palpable on bimanual vaginal examination. Seven women with complex
      type tumors underwent laparotomy and their pathological diagnoses revealed 3
      dermoid cysts, 3 endometrioid cysts and 1 ovarian cancer. Two women with cystic
      type tumors underwent laparotomy and their pathological diagnoses revealed 1
      paraovarian cyst and 1 endometrioid cyst. Many ovarian tumors were detected at
      prolonged cycle of menstruation and 69% of them disappeared in repeated TVS.
      Sixty percent of ovarian cystic tumors under 50 mm in diameter also disappeared
      in repeated TVS. Close attention to menstrual cycle and morphologic findings is
      needed to decrease false-positive cases in TVS screening for ovarian cancer.

PMID- 9261751
TI  - Mullerian adenosarcoma of the uterus.
AB  - A case of adenosarcoma of the uterus in a 59-year-old woman is here reported.
      Adenosarcoma is a low malignant potential tumor with a benign glandular and a
      malignant stromal component. The treatment is usually hysterectomy with bilateral
      salpingo-oophorectomy. Debated is the usefulness of adjuvant chemotherapy, while
      radiation treatment is not beneficial. Long term follow-up is necessary for these
      patients because of high recurrence risk, mostly in cases with myometrial
      invasion.

PMID- 9261752
TI  - Renal dysfunctions secondary to ifosfamide treatment in children.
AB  - With the increasing use of ifosfamide in pediatric tumors, nephrotoxicity became
      the point of interest since it may cause chronic morbidity. In this study, the
      renal glomerular and tubular functions of 25 cases with solid tumors aged between
      2-17 years (median 9) who were treated with ifosfamide, were investigated. For
      this purpose, routine blood urea, creatinine, calcium, phosphorus, electrolytes,
      urinary creatinine, phosphorus, glucose, protein and urinary retinol binding
      protein as well as microglobulin were evaluated. Except for two patients who had
      hypophosphatemia, phosphaturia, and proteinuria, all the cases had normal blood
      biochemistry, creatinine clearance, tubular phosphate reabsorption; and none had
      proteinuria, hematuria, or glycosuria. In spite of these findings, urine beta 2
      microglobulin and retinol binding protein were found to be high in 11 patients
      and this elevation persisted during the following one year in 8 cases whose
      treatments were stopped and their levels increased in three patients who
      continued to receive fosfamide therapy. In correlation with the increasing
      cumulative dose of ifosfamide (32-126 g/m2), urinary retinol binding protein or
      beta 2 microglobulin of patients who are treated with ifosfamide may predict the
      existence of renal toxicity even if other routine renal function tests are
      normal. Thus, the periodic evaluation of urinary beta 2 microglobulin and retinol
      binding protein in patients receiving chemotherapy containing ifosfamide is
      recommended.

PMID- 9261753
TI  - Mental state deficit evaluation by computerized test.

PMID- 9261754
TI  - Gene transfer, gentamicin resistance and enterococci.
AB  - Enterococci are versatile pathogens by virtue of their ability to exhibit low
      level intrinsic resistance to clinically useful antibiotics and their tolerance
      to adverse environmental conditions. In the last 20 years these pathogens have
      become progressively more difficult to treat because of their aptitude for
      acquiring antibiotic-resistance genes. Of increasing concern is the rapid
      dissemination of the AAC6'-APH2" bi-functional aminoglycoside modifying enzyme.
      This enzyme confers high-level resistance to gentamicin and all other related
      aminoglycosides with the exception of streptomycin. The gene conferring this
      phenotype has been associated with both narrow and broad host range plasmids, and
      has recently been found on conjugative transposons. The nature of these
      conjugative elements raises the possibility of the resistance gene spreading to
      other pathogenic bacteria.

PMID- 9261755
TI  - Epidemiological typing of Stenotrophomonas maltophilia.
AB  - Stenotrophomonas maltophilia is increasingly recognized as a cause of hospital
      acquired infection and respiratory tract colonization in cystic fibrosis
      patients. A number of methods have been described for the typing of strains in
      epidemiological studies. Pulsed-field gel electrophoresis (PFGE) of total
      chromosomal DNA cleaved by low-frequency restriction site endonucleases (XbaI,
      SpeI) is highly discriminatory and defines populations at the strain level. Other
      molecular methods such as ribotyping with restriction endonucleases (BamHI, ClaI,
      BelI, EcoRI) can be used to subdivide the species but with reduced discrimination
      compared with PFGE. Polymerase chain reaction (PCR) fingerprinting techniques
      utilizing random primers or those directed against repeat motifs (ERIC, REP) are
      rapid and offer high discrimination for the study of outbreaks. A consistent
      finding from a number of incidents is the high diversity of strain types of S.
      maltophilia identified and the low incidence of cross-infection between patients.

PMID- 9261756
TI  - A survey of the incidence and care of postoperative wound infections in the
      community.
AB  - The incidence of postoperative wound infection after clean surgery in the four
      weeks following early discharge from hospital and its effect on community medical
      services have been studied prospectively. The wound infection rate as assessed by
      118/155 patients who responded to a postoperative questionnaire was 9%; half of
      the wound problems presented after discharge. Postoperative wound infection
      increased the time spent by general practitioners per patient twofold, and that
      of practice/district nurses > or = fivefold.

PMID- 9261757
TI  - Surveillance of nosocomial infections in geriatric patients.
AB  - Prospective surveillance of hospital-acquired infections was undertaken in the
      geriatric ward of the University Hospital, Utrecht, the Netherlands. The medical
      records of 300 patients were studied for the presence of nosocomial infections
      using the criteria defined by the Centers for Disease Control (CDC), Atlanta,
      Georgia, USA. Data were collected from patients with and without infection, which
      allowed for the analysis of risk factors for nosocomial infection. In 100 out of
      300 patients (33.3%), a total of 126 infections was diagnosed. The incidence of
      nosocomial infections was 16.9 per 1000 days of stay in the hospital. The mean
      length of stay of patients with infection was 39 days, while that of patients
      without infection was 17.8 days. Infections developed after an average stay of
      13.3 days in the hospital. Patients with infections were 2.6 years older than
      patients without infections (P = 0.005). Dehydration was shown to be a major risk
      factor for infection (RR = 2.1, 95% CI: 1.4-3.2). Of the infections, 58.7% were
      urinary tract infections (UTIs, asymptomatic and symptomatic). The most important
      risk factor for an asymptomatic UTI was an indwelling urinary catheter (RR = 7.3,
      95% CI: 3.1-17.1). The duration of use of the indwelling urinary catheter was of
      significant influence in the development of a UTI. Seventy percent of the
      patients with an asymptomatic UTI were treated with antibiotics. Infections of
      the gastrointestinal tract accounted for 19.8% of all nosocomial infections. The
      majority of these infections were due to an outbreak of Clostridium difficile. In
      conclusion, the length of stay may be prolonged by a nosocomial infection. In
      this study, the main risk factors for developing a nosocomial infection were age,
      dehydration and the presence of an urinary catheter. Our observations showed that
      age is a predisposing factor for nosocomial infection and that the risk increases
      with each year, even for geriatric patients.

PMID- 9261758
TI  - Outbreak of gram-negative septicaemia caused by contaminated continuous infusions
      prepared in a non-clinical area.
AB  - An outbreak of Gram-negative septicaemia due to cross infection on an acute
      cardiology ward is reported. This outbreak was facilitated by two factors: first,
      an area originally designed for non-clinical purposes was converted into a clean
      utility area without consulting the infection control team, and second, changes
      in staff had taken place at the same time. This outbreak emphasizes the
      importance of continuous staff training in infection control, the involvement of
      the infection control team in all building alterations and the need to improve
      recommendations by the Department of Health in the design of clean utility areas.

PMID- 9261759
TI  - Simultaneous persistence of methicillin-resistant and methicillin-susceptible
      clones of Staphylococcus aureus in a neonatal ward of a Warsaw hospital.
AB  - Fifty-seven methicillin-resistant Staphylococcus aureus (MRSA) isolates from
      babies (N = 31), carriers amongst health care workers (N = 16; 10% of all staff
      members) and the environment (N = 10); 39 MSSA isolates, from babies (N = 18),
      health care workers (N = 5) and environment (N = 16) were analysed. The strains
      were from the neonatal ward of a teaching hospital in Warsaw and were collected
      over a period of 16 months (1993/1994). The isolates were characterized by phage
      typing, arbitrary-primed polymerase chain reaction (AP PCR), DNA repeat
      polymorphism within the protein A gene and the resistance pattern to
      antimicrobial agents. The presence of the mecA gene was determined by PCR. MRSA
      were classified as heterogeneously resistant to methicillin, susceptible to other
      antimicrobial agents and, except for three isolates, appeared to be genotypically
      almost identical. The first example of mupirocin resistant MRSA in Poland was
      documented. Amongst MSSA isolates, increased variability was seen, however, the
      persistence of one predominate clone of MSSA was shown. In this particular
      hospital environment, several different strains of both MRSA and MSSA were
      capable of maintaining persistent colonization.

PMID- 9261760
TI  - Inactivation of hepatitis B virus: evaluation of the efficacy of the disinfectant
      'Solprogel' using a DNA-polymerase activity assay.
AB  - The effects of sodium dichloroisocyanurate (NaDCC) and Solprogel (Laboratorios
      Inibsa, S.A., Barcelona, Spain), a compound that contains NaDCC plus a
      biodegradable polymer of acrylic acid, on the activity of DNA polymerase (DNA-P)
      associated with hepatitis B virus in serum were evaluated. DNA-P positive and
      negative pools of human serum samples were used as positive and negative stock
      virus. Inhibition of DNA-P activity by NaDCC and the commercial product was found
      to be concentration-dependent. Two minutes exposure to the minimum effective
      concentration of NaDCC (1000 ppm available chlorine) or Solprogel 16% (960 ppm
      available chlorine) totally inhibited DNA-P activity.

PMID- 9261761
TI  - Endoluminal brushing for detection of central venous catheter colonization--a
      comparison of daily vs. single brushing on removal.
AB  - The fibrin assay system (FAS) has been designed to address the problem of in-situ
      diagnosis of central venous catheter (CVC) colonization. The FAS was evaluated in
      12 critically ill patients with daily brushings, comparing results with culture
      of the catheter tip and blood. Data analysis of the FAS showed a sensitivity of 0
      with a specificity of 1.0. The study was repeated in a further 12 high-risk
      patients with a single terminal brushing on catheter removal. This gave a
      sensitivity of 0.14 and a specificity of 0.8. Differences in sensitivity may be
      due to daily disruption of the endoluminal fibrin clot. Our results do not
      support the routine use of the FAS to detect CVC colonization in the intensive
      care unit.

PMID- 9261762
TI  - A randomized trial of alcohol 70% versus alcoholic iodine 2% in skin disinfection
      before insertion of peripheral infusion catheters.
AB  - Skin disinfection before insertion of peripheral infusion catheters is standard
      practice, but a comparison in effectiveness of the two most widely used
      disinfectants is lacking. We compared alcohol 70% and alcoholic iodine 2% in a
      prospective randomized trial. Data from 109 patients on a pulmonary ward were
      analysed. Phlebitis occurred six times in the alcohol group and 12 times in the
      iodine group. This relative risk reduction of 53% failed to reach significance (P
      = 0.18). The power of the study, however, was only 0.55, meaning a 45% chance of
      missing a true difference. As countless catheters are inserted each year, a small
      difference in phlebitis rate could save discomfort to many patients. Thus, a
      larger trial seems warranted. The addition of theophylline to the prednisone
      infusion resulted in a significantly higher phlebitis rate: 27.3 versus 9.2% (P =
      0.03).

PMID- 9261763
TI  - Strategies for the management of healthcare staff colonized with epidemic
      methicillin-resistant Staphylococcus aureus.

PMID- 9261764
TI  - Hyaluronan polymer size modulates intraocular pressure.
AB  - To investigate whether the occasional increase in intraocular pressure that may
      arise following injection of sodium hyaluronan into the anterior segment during
      intraocular surgery is related to the polymer size of hyaluronan, controlled
      fragmentation of hyaluronan chains in vitro was obtained using progressive
      incubation with testicular hyaluronidase. The profile of molecular sizes of the
      hyaluronan polymers in various preparations was determined using molecular sieve
      column chromatography. Individual preparations were injected into six rabbit eyes
      and intraocular pressures were measured every one-half hour for 12 hours. Longer
      incubations of hyaluronan with hyaluronidase resulted in more extensive
      degradation with accumulation of shorter chain lengths. In the rabbit, mean
      intraocular pressure for 12 hours following intracameral injection of hyaluronic
      acid (HA) is proportional to the polymer size of HA. The occasional elevation of
      intraocular pressure that occurs following injection of hyaluronan during
      ophthalmic surgery can be avoided in part by assuring the rapid fragmentation of
      the large molecular size hyaluronan polymer.

PMID- 9261765
TI  - Dose-response study of dapiprazole HCl in the reversal of mydriasis induced by
      2.5% phenylephrine.
AB  - Dapiprazole HCL is currently available in the United States for reversal of
      diagnostic mydriasis. The recommended dosage for this indication is 2 drops
      followed 5 minutes later by 2 drops. We studied the dose-response profile and
      tolerance of three different treatment regimens: 1 drop alone, 1 drop followed by
      1 additional drop 5 minutes later, and 2 drops followed by 2 additional drops 5
      minutes later. Sixty normal male and female volunteers between 18 and 40 years of
      age were recruited for a double-masked, placebo-controlled, crossover study in
      which each eye of each subject was dilated with 2.5% phenylephrine. After one
      hour, one eye was treated with 0.5% dapiprazole, and the contralateral eye was
      treated with placebo. Each subject was treated with each of the three dapiprazole
      regimens in three different study sessions separated by at least 5 days (drug
      half-life in the eye is 5 hours). Analysis of AUC demonstrated no significant
      difference (P = 0.620) between the 1 drop regimen and the 2 + 2 regimen. A single
      drop of dapiprazole has a clinical effect equivalent to the 2 + 2 drop regimen in
      eyes dilated with 2.5% phenylephrine, which should improve the cost-effectiveness
      of this mydriolytic agent.

PMID- 9261767
TI  - Enhanced ocular hypotensive response to epinephrine in rabbits with prior
      dexamethasone treatment.
AB  - The purpose of this study was to determine glucocorticoid modulation of ocular
      pressure to epinephrine applied topically to rabbit eyes that were pretreated
      with dexamethasone. Rabbit eyes were pretreated with five applications of topical
      0.07% dexamethasone (0.1% dexamethasone phosphate) or saline drops, administered
      at ten minute intervals. The eyes were then treated with epinephrine bitartrate
      drops at concentrations of free base epinephrine of 1.1%, 0.27%, 0.05%, 0.027%,
      0.005% or 0.0005%. An additional group of rabbits received dexamethasone
      pretreatment only. Intraocular pressure (IOP) was measured for the next four
      hours. Enhanced lowering of intraocular pressure was observed with dexamethasone
      pretreatment. Rabbits receiving the smaller dose of epinephrine with
      dexamethasone had the largest decrease in IOP at 135 minutes after instillation
      of the epinephrine drops (0.005% epinephrine, mean difference +/- standard error
      of mean = 5.4 +/- 1.1 mmHg). Similarly, the duration of significant decrease of
      the IOP was prolonged in the groups receiving the lower concentrations of
      epinephrine (0.005% epinephrine, 255 minutes after administration of
      epinephrine). The synergism between glucocorticoids and adrenergic agonists in
      lowering IOP may be potentially useful in the therapy of ocular hypertension and
      glaucoma.

PMID- 9261766
TI  - Pharmacological evidence for thromboxane receptor heterogeneity--implications for
      the eye.
AB  - The pharmacological activity of two novel thromboxane A2 (TxA2)-mimetics,
      AGN191976 and AGN192093, was investigated in vitro, using standard organ bath
      assays and human platelets, to determine potency and selectivity at various
      prostanoid (PG-) receptors. The effects of these compounds on intraocular
      pressure in Beagle dogs were then compared with U-46619, a widely employed and
      structurally different TP-receptor agonist. AGN191976 and AGN192093 were highly
      potent TP-receptor agonists in the rat aorta (EC50 of 0.32 and 1.3 nM,
      respectively) and human myometrium. Both compounds were approximately 10 to 50
      fold more potent than U-46619. These contractile responses could be blocked with
      a potent TP-receptor antagonist, SQ29548. In human platelets, AGN191976 (EC50 =
      16.3 nM) and U-46619 (EC50 = 538.3 nM) potently stimulated aggregation (TP
      receptor mediated effect), whereas AGN192093 was a much weaker agonist (EC50 =
      37.9 microM). AGN192093 was not a partial agonist in platelets, since it did not
      antagonize aggregation induced by AGN191976, U-46619, arachidonic acid or ADP.
      These results provide evidence for a subdivision of TP-receptors, and AGN192093
      appears to be able to distinguish between TP-receptors in smooth muscle and
      platelets. In the Beagle dog eye, both AGN191976 and AGN192093 were highly potent
      and efficacious ocular hypotensives. Single 2.5 micrograms doses of drug
      decreased IOP by 11.4 (AGN191976) and 7.7 mm Hg (AGN192093) relative to the
      contralateral control eye. In contrast, U-46619 did not lower IOP. AGN191976, but
      not U-46619, increased outflow facility in these animals, which is consistent
      with their effects on IOP. Neither compound caused miosis which is FP-receptor
      mediated in the dog. These studies suggest the existence of heterogeneous
      populations of TP-receptors. AGN191976 and AGN192093, two novel TP-receptor
      agonists, appear to be useful tools for the pharmacological distinction of TP
      receptor subtypes.

PMID- 9261768
TI  - Pharmacological analysis of mast cell mediator and neurotransmitter receptors
      coupled to adenylate cyclase and phospholipase C on immunocytochemically-defined
      human conjunctival epithelial cells.
AB  - We sought to establish and immunocytochemically characterize primary cultures of
      human conjunctival epithelial (HCE) cells, and to determine the types of
      receptors coupled to adenylate cyclase (AC) and phospholipase C (PLC) present on
      them which may be stimulated following allergic or inflammatory provocation of
      the tissue. HCE cells possessed the key epithelial cell surface cytokeratins AE1,
      AE3 and AE5. Signal transduction studies (n > or = 3), using agonists and
      antagonists, revealed the presence of beta 2-adrenergic (isoproterenol EC50 = 5.2
      nM), prostaglandin E2 (EC50 = 168 nM) and vasoactive intestinal peptide (EC50 =
      0.69 nM) receptors positively coupled to AC in HCE cells. Bradykinin (EC50 = 0.83
      nM), platelet activating factor (EC50 = 4.5 nM), leukotriene C4 (EC50 = 300 nM)
      and histamine1 (EC50 = 3.1 microM) receptors were coupled to PLC (n = 3 for
      each). These data suggest that HCE cells in vivo may represent target cells for
      mast cell mediators and certain neurotransmitters which are released into the
      tear-film upon allergic provocation of the conjunctiva.

PMID- 9261769
TI  - The effects of elevated glucose on Na+/K(+)-ATPase of cultured bovine retinal
      pigment epithelial cells measured by a new nonradioactive rubidium uptake assay.
AB  - The effects of stimulated hyperglycemia on the Na+/K(+)-ATPase activity of
      cultured bovine retinal pigment epithelial (RPE) cells were investigated. Total
      Rb+ uptake, measured by a chromatographic method, was decreased 20-30% by 55.5 mM
      glucose relative to 5.55 mM glucose for culture periods of 2 to 28 days. An acute
      hyperglycemic stress (< 1 week) had no effect on ouabain-inhibition of Rb+ uptake
      or ouabain binding to RPE cells (IC50 = 55 nM for both processes) and did not
      alter the IC50 value (near 10 nM) for binding of strophanthidin, another
      selective Na+/K(+)-ATPase inhibitor. A small increase in the apparent K(m) of Rb+
      for Na+/K(+)-ATPase accompanied the decrease in maximal Rb+ uptake at 55.5 mM
      glucose. The continuous presence of AL-1576, an aldose reductase inhibitor (ARI),
      normalized the effect of severe hyperglycemia on Rb+ uptake in the chronic (28
      days) but not the acute exposure protocols. Thus, decreased efficiency of
      Na+/K(+)-ATPase caused by chronic accumulation of intracellular sorbitol can
      account for previously reported functional and structural alterations in the RPE
      cell layer of diabetic rodents. The results of the present study suggest that
      hyperglycemia-induced loss of Na+/K(+)-ATPase function in RPE cells, which
      responds to aldose reductase inhibitor treatment, contributes to the pathogenesis
      of diabetic retinopathy.

PMID- 9261770
TI  - Pharmacological evaluation of anti-inflammatory pyrrole-acetic acid derivative
      eye drops.
AB  - The effects of mucoadhesive eye drops containing a pyrrole-acetic acid derivative
      (tolmetin) at 0.5% concentration on ocular inflammation produced by sodium
      arachidonate in the rabbit's eye were evaluated. Furthermore, the bioavailability
      of the mucoadhesive formulation in the aqueous humor against an aqueous-based
      solution was compared. Tolmetin eye drops significantly reduced the signs of
      ocular inflammation elicited by sodium arachidonate on conjunctiva and iris.
      Tolmetin treatment significantly reduced the levels of prostaglandin E2,
      polymorphonuclear leukocytes and protein concentration in aqueous samples
      obtained from the eyes treated with arachidonate. The de novo production of
      prostaglandin E2 by corneas obtained from rabbits sacrificed 2 hours after
      arachidonate instillation were significantly higher in samples taken from
      controls than in corneas obtained from the eyes treated with tolmetin eye drops.
      Furthermore, the drug treatment significantly reduced the rise in intraocular
      pressure arachidonate-induced. The mucoadhesive formulation showed a higher
      bioavailability in aqueous humor compared to the aqueous-based solution both in
      the uninflamed and in the inflamed rabbit eyes.

PMID- 9261771
TI  - Efficacy of oxymetazoline eye drops in non-infectious conjunctivitis, the most
      common cause of acute red eyes.
AB  - Oxymetazoline (OMZ) is an alpha-adrenergic agonist which causes potent
      vasoconstriction in various tissues. Thus, its effects on red eye conjunctivitis
      induced by histamine and arachidonic acid were tested in rabbit eyes. It was
      found that a brief conjunctivitis induced by 0.01% of histamine can be eliminated
      effectively by 0.001, 0.004, and 0.016% of OMZ. The long lasting conjunctivitis
      induced by 0.3% arachidonic acid can also be markedly reduced by 0.004, 0.008,
      and 0.016% of OMZ. These results indicate that OMZ is a potent, long acting
      decongestant for conjunctival red eye syndrome.

PMID- 9261772
TI  - Retinal safety of oral and topical ofloxacin in rabbits.
AB  - Ofloxacin is a broad spectrum fluoroquinolone antibiotic with good ocular
      penetration. We investigated the potential for retinal toxicity associated with
      increased intraocular penetration following intensive topical, oral, and combined
      topical and oral administration. We confirmed ofloxacin concentrations in aqueous
      and vitreous following these forms of administration. Rabbits received either
      topical, oral, or a combination of oral and topical ofloxacin. Topical
      administration consisted of one drop of ofloxacin 0.3% drops given every thirty
      minutes for a total of eight doses. Oral ofloxacin was administered at a dose of
      10 mg (4 mg/kg for average weight 2.5 kg rabbit) every 12 hours for a total of
      three doses. Six rabbits were followed longitudinally for 4 weeks for evidence of
      retinal toxicity by indirect ophthalmoscopy and serial ERGs. Electron and light
      microscopic histopathologic examination of the retina were performed 4 weeks
      following drug administration. To verify intraocular penetration, ten rabbits
      received identical dosing schedules followed by HPLC measurement of aqueous and
      vitreous drug concentrations at 1, 4, 8, 12, and 24 hours following dose
      completion. No evidence of retinal toxicity was detected by indirect
      ophthalmoscopy, electroretinography, or histopathological examination. Vitreous
      ofloxacin levels were highest after combined oral and topical administration,
      peaking at 0.892 microgram/ml 8 hours following dosage completion. The peak
      vitreous level following oral administration was 0.230 microgram/ml and 0.026
      microgram/ml following topical administration. Peak aqueous humor levels were
      achieved one hour following drug administration and were 11.400 micrograms/ml
      after topical, 0.206 microgram/ml after oral, and 8.180 micrograms/ml after
      combined administration. Our study suggests that intensive topical and oral
      ofloxacin administration does not cause retinal toxicity in rabbits, despite
      achieving effective aqueous and vitreous humor antimicrobial concentrations.

PMID- 9261773
TI  - The distribution of total, free, short-chain acyl and long-chain acyl carnitine
      in ocular tissues of the camel (Camelus dromedarius).
AB  - Carnitine (CA) plays an important role in the metabolism of fatty acids. Its
      presence is considerable in tissues that utilize fatty acids as an important
      source of energy, such as the heart and the skeletal muscle. The presence of
      free, short-chain acyl and long-chain acyl carnitine was shown for the first time
      in various tissues of the camel eye. The ratio of acyl carnitine (AC) to free
      carnitine (FC) was high in aqueous humor, indicating a predominance of AC, while
      it was low in vitreous humor, indicating a higher concentration of FC. The
      highest concentration of total carnitine (TC) was observed in the retina,
      followed by the cornea, while the lowest was found in lens nucleus. Among various
      forms, FC concentration was the highest in the cornea while it was the lowest in
      the lens cortex. In the cornea and retina, the proportion of short-chain
      acylcarnitines (SC) was two-fold when compared to long-chain acylcarnitines (LC),
      while in the lens it was the same. The ratio of AC to FC in the retina was high,
      indicating a predominance of AC, while in lens it was low, indicating a higher
      concentration of FC. In contrast, L-CA in the cornea was present equally between
      the free and the esterified forms. The quantitative differences in the
      distribution of L-CA in various tissues of the camel eye reflect that it may be
      involved in providing a source of readily available energy.

PMID- 9261774
TI  - Prevention of thromboembolism in spinal cord injury. Consortium for Spinal Cord
      Medicine.

PMID- 9261775
TI  - Acute management of autonomic dysreflexia: adults with spinal cord injury
      presenting to health-care facilities. Consortium for spinal cord.

PMID- 9261776
TI  - Ultrastructural characteristics of glutamatergic and GABAergic terminals in cat
      lamina IX before and after spinal cord injury.
AB  - The present study was designed to: 1) morphologically characterize cat glutamate
      and GABAergic synaptic terminals in lamina IX in the intact spinal cord at the
      electron microscopic level using postembedding immunochemical techniques and .2),
      begin an analysis of how the synaptic architecture of glutamate and GABAergic
      terminals changes after an ipsilateral spinal cord hemisection. The present study
      shows that glutamate immunoreactive terminals are characterized by a wide
      synaptic cleft, asymmetric synaptic membrane densities and spherical synaptic
      vesicles. Most of the glutamatergic terminals are presynaptic to small or medium
      size dendrites. In contrast, GABAergic terminals display typical pleomorphic
      synaptic vesicles, a narrow synaptic cleft and a symmetrical membrane density.
      Qualitative analysis indicated that 13-17 months after hemisection, the length of
      the synaptic active zones in both glutamatergic and GABAergic terminals
      ipsilateral to hemisection is longer than those observed in the terminals
      contralateral to hemisection orfin normal control cats. Furthermore, the
      perimeters of both dendrites and either glutamate or GABA immunoreactive
      terminals are longer on the hemisected side compared with those observed in the
      nonhemisected side of the spinal cord. The results are important for complete
      understanding of the mechanisms which underlie locomotor recovery in mammals
      following spinal cord injury.

PMID- 9261777
TI  - Short-term bladder-wall response to implantation of microstimulators.
AB  - This study examined the histological response of the bladder wall serosa to the
      implantation of wireless microstimulators secured with a single polypropylene
      suture. Two to three microstimulators were implanted in each of three casts for
      an eight week implantation period to allow sufficient time for a bladder-wall
      injury-response to develop. Gross observation revealed encapsulation of the
      microstimulators with no perforation to the bladder lumen or migration from the
      bladder wall. Histological evaluation confirmed that all the microstimutators
      were encapsulated with a thin connective tissue sheath and a thickened subserosal
      layer. There was no remarkable difference in tissue morphology compared with
      normal bladder wall sections for five of seven stimulators. Two microstimulators
      in one cat revealed a moderate to severe inflammatory response confined to a
      small area around the stimulator. In a second cat, a suture extended through the
      bladder wall. The microstimulators were observed with a scanning electron
      microscope after explantation. The electrode surfaces, bonding interface between
      silicon and glass and insulating films that were exposed to biological fluids
      were carefully inspected. All these observations indicate that the glass capsule
      reliably protected the sealed cavity of the microstimulators from moisture. These
      results indicate the microstimulator should be considered for further studies
      such as effects of stimulation and long-term implantation.

PMID- 9261778
TI  - Manual muscle test score and force comparisons after cervical spinal cord injury.
AB  - Manual muscle test scores (MMTS) and maximum voluntary contraction (MVC) force
      measurements were made from triceps brachii muscles of 70 individuals with
      chronic cervical spinal cord injury (SCI). Both MMTS and strength assessments
      showed that asymmetrical motor deficits were common. Muscles with MMTS of 3
      generated an average of nine percent MVC force produced by control muscles. In
      this SCI population, little residual voluntary force is apparently needed for
      triceps brachii to work against gravity. Only 24 percent of muscles tested had
      this strength, however, indicating the need to develop strategies to alleviate
      this muscle weakness. MMTS and force were related positively but each MMTS was
      not associated with a unique force range. MVC force generating capacity is
      therefore only one factor that determines whether or not a muscle can work with
      or against gravity and against resistance.

PMID- 9261779
TI  - Effect of timing of stabilization on length of stay and medical complications
      following spinal cord injury.
AB  - This retrospective study examines length of acute hospital stay (LOS) and the
      development of medical complications in 64 patients with cervical, thoracolumbar
      or cauda equina injuries divided into two groups according to whether they
      underwent spinal stabilization < 24 hours after injury or > 24 hours after
      injury. The mean length of stay for the early stabilization group was 37.5 days
      (SD +/- 34.2) and for the late stabilization group 54.7 days (SD +/- 40.1). This
      difference was statistically significant by Mann Whitney U test (Z = 2.53, P =
      0.01). There was no statistically significant difference between the early and
      the late groups with respect to the occurrence of common medical complications.
      There was a statistically significant difference in age in the early group (mean
      of 32.4 years) versus the late group (mean of 41.9 years) (t = 2.36, P = 0.02);
      however we do not feel that this age difference is clinically significant. There
      was not a statistically significant difference between the early group (17.9, SD
      = +/-7.2) and the late group (21.3, SD = +/- 8.3) (t = 1.71, p = 0.10) in mean
      injury Severity Scores (ISS). Also the correlation between length of stay and ISS
      scores was not significant (r = 0.18, P = 0.2). Timing of spinal stabilization
      appears to be an important factor in the management of spinal cord injury
      survivors. Our limited retrospective study suggests that when spinal
      stabilization is indicated, performance < 24 hours after injury is associated
      with a significantly shorter length of stay in the hospital. We suspect this is
      due to earlier mobilization of the patient. Medical complication rates were not
      significantly affected.

PMID- 9261780
TI  - Anemia and serum protein deficiencies in patients with traumatic spinal cord
      injury.
AB  - This study was conducted to further investigate the natural history of the
      anemia, hypoproteinemia and hypoalbuminemia commonly observed in patients with
      traumatic spinal cord injury (SCI). Blood samples were taken from 46 traumatic
      SCI patients at the time of initial admission to an acute rehabilitation hospital
      and again approximately one year later during a routine follow-up appointment. At
      initial admission, 65 percent of patients were anemic (hemoglobin < 13.0 g/dl),
      86.7 percent were hypoalbuminemic (albumin < 3.2 g/dl) and 48.9 percent were
      hypoproteinemic (total protein < 6.5 g/dl). Deficiencies were most commonly
      observed in tetraplegics and in patients with complete injuries. At the time of
      follow-up, 6.8 percent of patients were anemic, 2.2 percent demonstrated
      abnormally low serum protein concentrations and a significant (p = 0.01) decrease
      in the incidence of each deficiency was observed. Our findings suggest that
      anemia and decreased serum protein concentrations, while commonly observed in the
      acute SCI population, are much less frequently encountered in the more
      chronically injured. If noted in the chronic SCI patient, these deficiencies
      should alert clinicians to the likelihood of a concurrent process.

PMID- 9261781
TI  - Impact of peripherally inserted central catheters on phlebitic complications of
      peripheral intravenous therapy in spinal cord injury patients.
AB  - We investigated the impact of peripherally inserted central catheter (PICC)
      placement in spinal cord injury patients at high risk for infusion phlebitis. The
      rate and etiology of phlebitis was investigated in two phases. During Phase I,
      peripheral IV cannulae and conventional central venous catheters (CVC) were used.
      During Phase II, patients identified to be at risk for phlebitis received PICCs.
      The number of peripheral IVs, CVCs and PICCs was tabulated for both phases of the
      study. Technical, infectious and thrombotic complications were studied
      prospectively for PICCs and retrospectively for CVCs. We found the rate of
      phlebitis was 16.5 percent and 2.4 percent for Phases I and II, respectively (p =
      0.0002). Three infections occurred in 38 PICCs and one infection was documented
      in 13 conventional CVCs. The number of peripheral IVs and conventional CVCs was
      reduced significantly from Phase I to Phase II. No procedural complications,
      catheter sepsis or clinically apparent venous thrombosis occurred. In conclusion,
      PICCs reduced the rate of phlebitis thresholds with a low complication rate and
      reduced the use of peripheral IVs and conventional CVCs.

PMID- 9261782
TI  - Autonomic dysreflexia/hyperreflexia.
AB  - As alluded to at the onset, our purpose is to provide a periodic reminder about
      autonomic dysreflexia/hyperreflexia (AD). Some historical background was offered
      since so much of the recent literature has been obtained from Medline which
      started in 1966. There were a number of early pioneers who first labored with AD.
      Kewalramani, in his fine paper, found various names for AD in the literature:
      sympathetic hyperreflexia, paroxysmal hypertension, spinal poikilopiesis,
      autonomic spasticity, paroxysmal hyperactive autonomic reflexes and paroxysmal
      neurogenic hypertension. Why not use only one term for this life threatening
      syndrome: autonomic dysreflexia/hyperreflexia.

PMID- 9261783
TI  - Autonomic dysreflexia: pharmacological management of hypertensive crises in
      spinal cord injured patients.
AB  - Interruption of autonomic pathways by spinal cord injury (SCI) causes
      dysfunctional autonomic dysreflexia (AD), which was first described in 1917,
      still remains unrecognized by those in the medical profession not involved in SCI
      care. Autonomic dysreflexia is a syndrome generally manifest by cardiovascular
      symptoms and characterized by paroxysmal hypertension. These symptoms appear in
      patients with spinal cord injury above the sympathetic outflow from the spinal
      cord (T6). Since patients with high level SCI are usually hypotensive, the high
      blood pressures that develop during AD represent pressure changes of a magnitude
      that can cause cerebrovascular accidents and death of the subject. We discuss the
      therapeutic interventions that abate and curtail the symptoms and prevent the
      catastrophic sequelae of autonomic dysreflexia.

PMID- 9261784
TI  - Surgical aspects of autonomic dysreflexia.
AB  - Autonomic dysreflexia (AD) is a characteristic syndrome that occurs in spinal
      cord injury (SCI) patients with lesions above the sympathetic outflow at T6 and
      rarely in those with lesions below T10. Symptoms are initiated by noxious stimuli
      below the level of injury which result in massive sympathetic discharges from the
      isolated cord. These produce what may be called a sympathetic storm manifest by
      severe life threatening hypertension. Anesthesiologists and surgeons dealing with
      SCI patients must know how to recognize this syndrome, how to prevent its
      occurrence and how to manage it aggressively. Choice of anesthesia is frequently
      difficult and, in particular, it may be difficult to decide which type of
      anesthesia is best for patients susceptible to the syndrome. Therefore, we have
      conducted a retrospective study of SCI patients in the Department of Veterans
      Affairs Medical Center, Long Beach, California, where the Spinal Cord Injury
      Service is one of the largest in the country.

PMID- 9261785
TI  - Autonomic dysreflexia and detrusor-sphincter dyssynergia in spinal cord injury
      patients.
AB  - This study reevaluates the significance of our previously reported blood pressure
      monitoring during cystometrographic studies in spinal cord injury patients who
      had detrusor-sphincter dyssynergia. We have now evaluated 26 spinal cord injury
      patients (21 tetraplegics and five high paraplegics) with complex urodynamic
      studies both before and after transurethral modified sphincterotomy (TURS). In
      these patients, mean systolic rise prior to TURS was 32.4 mm Hg (S.D. +/- 16.3)
      and diastolic rise was 14.3 mm Hg (S.D. +/- 9.3). Following TURS, mean systolic
      rise was 15.5 +/- 0.1 and diastolic rise was 7.3 +/- 8.6. This is a statistically
      significant difference (p value .001). Following TURS, blood pressure rises were
      transitory and not associated with significant symptoms of autonomic dysreflexia.
      The present study confirms our previous findings that a high correlation exists
      between the magnitude of blood pressure response, level of injury and severity of
      detrusor-sphincter dyssynergia. These results indicate that following the
      modified external sphincterotomy, there was a significant reduction in the
      dysreflexic response during cystomanometry of the bladder (CMG). The potential of
      a significant rise in blood pressure during CMG makes it necessary to monitor
      blood pressure during these studies and be prepared to expediently deflate the
      bladder to prevent an inordinate rise in blood pressure, preventing cerebral
      vascular complications. Patients with a significant rise in blood pressure during
      CMG are at risk for severe dysreflexia when their bladder is full and require
      management strategies to optimize control of blood pressure response with
      medication and/or transurethral surgery.

PMID- 9261786
TI  - Pregnancy and delivery in tetraplegic women.
AB  - Increase in survival of spinal cord injured (SCI) women, society's acceptance
      that their lives should be similar to those of non-disabled women and their
      better general health are increasing the number of SCI women who become pregnant
      and will be delivered of a child. Vaginal delivery is preferred. Any SCI woman
      whose level is at T6 or higher is at risk for acute autonomic hyperreflexia as a
      result of uterine contractions. If induction is with Pitocin/Oxytocin, the risk
      is even greater. Communication with the woman's obstetrician is essential. The
      patient should be provided with a packet of information to share with the
      obstetrician. This should be followed with a phone call from the SCI physician to
      the obstetrician. Effective management includes epidural anesthesia; vacuum
      extraction is helpful in the expulsion stage. Episiotomy is usually not needed
      since the pelvic floor is relaxed. In addition, there is an increased incidence
      of dehiscence since SCI women should be mobilized early and need to transfer in
      and out of a wheelchair. Blood pressure needs to be taken during the peak of
      contraction. This needs to be compared to prenatal blood pressures. If prenatal
      blood pressure is 80/60 or 90/60 but during contraction is 130/80 with a pounding
      headache, that indicates autonomic hyperreflexia which is an indication for
      epidural anesthesia. With improvement of acute care and more effective
      rehabilitation, pregnancy and delivery in spinal cord injured (SCI) women will
      occur more frequently. No one has any great experience with this situation and
      most articles report only a few cases. Even the report by Goller and Paeslack4
      dealt with 175 cases from 42 centers in 24 countries. Most women were paraplegic
      and several who were injured early in their pregnancy had abnormal babies
      (possibly due to x-rays taken for spinal injury). Our spinal cord injury staff
      were pleased when we had two tetraplegic patients who were pregnant. It helped
      confirm our belief that life and its functions continue after paralysis. Staff
      members were involved in prenatal care, were present during delivery and were
      involved with postnatal care. Even more important is the fact that rehabilitation
      from the start was oriented with child care in mind. Occupational therapists used
      their skills and imagination to develop a program for newborn baby care by the
      tetraplegic mother.

PMID- 9261787
TI  - Efficacy of laser-assisted uvulopalatoplasty.
AB  - BACKGROUND AND OBJECTIVE: Laser-assisted uvulopalatoplasty (LAUP) is being used
      increasingly as a surgical treatment for snoring and obstructive sleep apnea
      (OSA). There is limited evidence for the success of LAUP in eliminating OSA. This
      study assesses the efficacy of LAUP in eliminating snoring and OSA and addresses
      which patients may be the best candidates for LAUP treatment. STUDY
      DESIGN/MATERIALS AND METHODS: From January 1994 to January 1996, 297 patients
      were evaluated for snoring, with 190 (64%) exhibiting some degree of OSA
      documented by a PSG: 41/ 190 (22%) mild OSA; 33/190 (17%) moderate OSA; 85/190
      (45%) severe OSA; 31/190 (16%) severity unknown. Ninety patients (90/ 297) have
      undergone LAUP treatment: 58/90 (64%) with OSA and 32/90 (36%) with snoring only.
      RESULTS: Our results indicate a significant reduction of snoring in patients
      without OSA, but diminishing success in patients with increasing degrees of OSA.
      Additionally, LAUP was not efficacious in treating OSA: pre-op respiratory
      disturbance index (RDI) of 10.8 vs. post-op RDI of 19.5 for mild OSA (P = 0.14);
      pre-op RDI of 22.9 vs. post-op RDI of 25.4 for moderate OSA (P = 0.43); pre-op
      RDI of 56.8 vs. post-op RDI of 46.3 (P < 0.05), which is statistically but not
      clinically significant (i.e., RDI remained in the severe range). CONCLUSION: We
      conclude that LAUP is an effective treatment for nonapneic snoring, but does not
      provide sufficient resolution of OSA, and based on our results, LAUP should be
      considered as an adjunctive therapy rather than a sole treatment for OSA in most
      cases.

PMID- 9261788
TI  - CO2 laser surgery for verrucous carcinoma of the larynx.
AB  - BACKGROUND: The verrucous carcinoma (VC) is a low grade malignant tumor.
      Treatment strategies of VC of the larynx are topics of the ongoing discussion,
      and the role of the carbon dioxide laser therapy in the management remains
      unclear to date. STUDY DESIGN/MATERIALS AND METHODS: From 1986 to 1995, 21
      patients with glottic VC were treated with transoral carbon dioxide laser
      surgery. Follow-up ranged from 6 to 122 months (mean 52). RESULTS: In T1 lesions,
      a complete removal of the tumor was possible with laser-cordectomy in ten cases
      and with extended laser cordectomy in four cases. In seven patients suffering
      from T2 carcinoma, a partial laser laryngectomy was performed. There was no tumor
      related death in this series. No patient required laryngectomy or radiotherapy.
      CONCLUSION: The results presented here are superior to those previously reported
      with radiotherapy. They add further support to the observation that surgery is
      the better treatment option for VC of the larynx. Based on the results of this
      study, recommended treatment for T1 and T2 VC is oncologic CO2 laser surgery in
      combination with a meticulous follow up for early recognition of local
      recurrence.

PMID- 9261789
TI  - In vivo light transmission spectra in EMT6/Ed murine tumors and Dunning R3327 rat
      prostate tumors during photodynamic therapy.
AB  - BACKGROUND AND OBJECTIVE: Variations in the optical coefficients in tissue and
      the photosensitizer during photodynamic therapy (PDT) will require adjustment of
      the light dose during the course of therapy. We have studied the dynamics using
      light transmission spectra for two different tumor models when tetrasulfonated
      aluminum phthalocyanine (AlPcS4) was used as photosensitizer. STUDY
      DESIGN/MATERIALS AND METHODS: Spectra were measured noninvasively in the EMT6/Ed
      murine tumor model, and with interstitially implanted source and probe fibers in
      the Dunning R3327-AT rat tumor model. Measurements were performed in the range
      600-840 nm, using a tunable dye laser, a diode laser, and a Ti:Sapphire laser.
      AlPcS4 has absorption in the range 600-700 nm with an absorption peak at 670 nm
      in saline. RESULTS: The in vivo spectrum of AlPcS4 both in the EMT6/Ed tumor
      model and the Dunning R3327-AT tumor model differs from the spectrum of AlPcS4 in
      saline. The absorption at 670 nm was reduced, whereas the absorption at 640 nm
      increased. Exposure of phototherapeutic levels of light caused reduced light
      absorption by the photosensitizer and further spectral shift. CONCLUSION: We
      found that the AIPcS4 absorption spectrum changes in a biological environment,
      and we also observed increased light transmission at the treatment wavelength
      during PDT in both tumor models. Instability in the absorption spectrum of the
      photosensitizer may influence the effectiveness of PDT.

PMID- 9261790
TI  - Laser-activated solid protein bands for peripheral nerve repair: an vivo study.
AB  - BACKGROUND AND OBJECTIVE: Severed tibial nerves in rats were repaired using a
      novel technique, utilizing a semiconductor diode-laser-activated protein solder
      applied longitudinally across the join. Welding was produced by selective laser
      denaturation of solid solder bands containing the dye indocyanine green. STUDY
      DESIGN/MATERIALS AND METHODS: An in vivo study, using 48 adult male Wistar rats,
      compared conventional microsuture-repaired tibial nerves with laser solder
      repaired nerves. Nerve repairs were characterised immediately after surgery and
      after 3 months. RESULTS: Successful regeneration with average compound muscle
      action potentials of 2.5 +/- 0.5 mV and 2.7 +/- 0.3 mV (mean and standard
      deviation) was demonstrated for the laser-soldered nerves and the sutured nerves,
      respectively. Histopathology confirmed comparable regeneration of axons in laser-
      and suture-operated nerves. CONCLUSION: The laser-based nerve repair technique
      was easier and faster than microsuture repair, minimising manipulation damage to
      the nerve.

PMID- 9261791
TI  - Effect of pulsed Nd:YAG laser radiation on action potential conduction in
      isolated mammalian spinal nerves.
AB  - BACKGROUND AND OBJECTIVE: Dental lasers are claimed to produce analgesia, but the
      mechanisms and extent of any effects are uncertain. This study investigated the
      effects of lasing on nerve conduction in isolated nerves. STUDY DESIGN/MATERIALS
      AND METHODS: Pulsed Nd:YAG laser energy was applied to spinal nerves in vitro and
      effects were measured as attenuation of the compound action potential (CAP)
      evoked by electrical stimulation. RESULTS: Lasing for 1 minute at 0.3-3.0 W
      caused a dose-dependent attenuation of all components of the CAP (P < 0.03). With
      0.3-1.0 W power, the CAP recovered to > 95% of the control levels 7 minutes after
      lasing; recovery was incomplete after lasing at > 2.0 W. CONCLUSION: Isolated
      nerves were remarkably tolerant of lasing. The degree of nerve conduction block
      increased with laser power. The data indicate that lasing could diminish
      sensations, including pain, mediated by peripheral nerves in soft tissues.

PMID- 9261792
TI  - Ultraviolet laser-induced fluorescence of human stomach tissues: detection of
      cancer tissues by imaging techniques.
AB  - BACKGROUND AND OBJECTIVE: The background for this work was several literature
      reports on applications of the fluorescence methods to detection and localization
      of human cancers. The objective of our study has been to investigate if such an
      approach could be applied for the detection of gastric cancers. STUDY
      DESIGN/MATERIALS AND METHODS: Our study was designed in such a way that
      spectrally resolved images of laser-induced fluorescence of human gastric mucosa
      were collected and assessed from a point of view of elaborating an algorithm
      allowing for a differentiation between malignant and premalignant lesions and
      areas of normal mucosa. The method involved exciting the autofluorescence with
      ultraviolet light (325 nm, He-Cd laser). The images were recorded in vitro in six
      regions of a visible spectrum using a cooled CCD camera. The material for study
      was 21 resected specimens for which altogether 72 surface areas were examined.
      RESULTS: The main result is the observation that a difference of the fluorescence
      intensities measured at 440 nm and 395 nm, both normalized to intensity measured
      at 590 nm, differs significantly for the tissues of interest. CONCLUSION: Using
      that difference as a diagnostic parameter, it was possible to classify malignant
      tumor tissues with a sensitivity of 96% and a predictive value of 42%, whereas
      the same approach applied to abnormal but not tumor stomach tissues gave values
      of 80%, and 98%, respectively.

PMID- 9261793
TI  - Giant cell formation in cells exposed to 740 nm and 760 nm optical traps.
AB  - BACKGROUND AND OBJECTIVE: Optical trapping is becoming a useful and widespread
      technique for the micromanipulation of cells and organelles. Giant cell formation
      following optical trapping was studied to detect the potential adverse effects.
      STUDY DESIGN/MATERIALS AND METHODS: The nuclei of preselected single CHO cells
      were exposed to 740 nm and 760 nm laser microbeam generated by a titanium
      sapphire tunable laser at 88 and 176 mW and different time exposures. The
      irradiated single cells were recorded and observed morphologically following
      exposure. Giant cells were tabulated and photographed. RESULTS: The irradiated
      cells either failed to divide, or they underwent nuclear proliferation to form
      giant cells through endoreduplication. CONCLUSION: Giant cells were induced by
      both 740 nm and 760 nm. The frequency of giant cell formation was higher for the
      longer time exposures and at the higher power densities. The use of an optical
      etalon to remove intracavity mode beating and high peak powers of the titanium
      sapphire laser caused a significant reduction in the formation of giant cells.

PMID- 9261794
TI  - Propagation of fluorescent light.
AB  - BACKGROUND AND OBJECTIVE: In general, the remitted fluorescence spectrum is
      affected by the scattering and absorption properties of tissue. Other important
      factors are boundary conditions, geometry of the tissue sample, and the quantum
      yield of tissue fluorophores. Each of these factors is examined through a series
      of Monte Carlo simulations. STUDY DESIGN/MATERIALS AND METHODS: Monte Carlo
      modeling is used to simulate the propagation of excitation light and the
      resulting fluorescence. Remitted fluorescence is determined for semi-infinite
      single and multiple layer geometries and for cubic geometries representing small
      tissue samples. Monte Carlo results are compared to approximations obtained with
      a heuristic model. RESULTS: Remitted fluorescence as a function of (1) the depth
      of fluorescence generation and (2) radial escape position is presented for semi
      infinite single and multiple layer geometries. Fluorescence from a small tissue
      sample is simulated in terms of a cubic geometry, and losses from the sides and
      bottom are presented as a function of cube dimensions in terms of optical depth
      of the excitation wavelength. Monte Carlo results for a homogeneous semi-infinite
      layer are compared to a simple, fast heuristic model. CONCLUSION: Both Monte
      Carlo simulations and the heuristic model clearly detail the volume of tissue
      interrogated by fluorescence. Since approximately 35-40% of the remitted
      fluorescence is due to photons originally directed away from the surface, distal
      layers affect the remitted fluorescence. Fluorescence spectra from small biopsy
      samples may not produce the correct line shape owing to wavelength dependent
      losses.

PMID- 9261795
TI  - Ablation rate of PMMA and human cornea with a frequency-quintupled Nd:YAG laser
      (213 nm).
AB  - BACKGROUND AND OBJECTIVE: As an alternative to the standard excimer laser used
      for PRK, we investigated the ablation rate at 213 nm of PMMA, and human corneas
      under controlled hydration. STUDY DESIGN/MATERIALS AND METHODS: The output of a
      frequency-quintupled Nd:YAG laser (213 nm) was transformed into a quasi-Gaussian
      beam. PMMA and corneal lenticules maintained under controlled hydration were
      ablated until perforation was detected. RESULTS: The ablation rate of PMMA and
      cornea at 213 nm were similar to that at 193 nm when radiant exposure was below
      200 mJ/cm2 and increased gradually between one and two times faster than that at
      193 nm when radiant exposure was > 200 mJ/ cm2. CONCLUSIONS: PMMA and cornea
      ablation at 213 nm are similar to that at 193 nm and are different from that at
      248 nm. The difference between PMMA and cornea ablation rates should be
      considered when using PMMA to test ablated diopter and smoothness for
      photorefractive surgery.

PMID- 9261796
TI  - Ablation of human nail by pulsed lasers.
AB  - BACKGROUND AND OBJECTIVE: The hard and resistant structure of the nail plate
      forms a natural barrier that limits the penetration of topical drugs. To overcome
      this barrier, the use of pulsed laser systems has been suggested. The purpose of
      this study was to evaluate the effect of four laser systems on nail plate
      ablation rates, ablation efficiencies, and subsequent craters morphology. STUDY
      DESIGN/MATERIAL AND METHODS: Solid state Er:YAG (2.94 microns, 250 microseconds),
      a Ho:YSGG (2.08 microns, 250 microseconds), a XeC1 Excimer (308 nm, 15 ns), and a
      novel solid-state ultrashort pulse laser (1.05 microns, 350 fs) were used.
      Ablation rates, surface morphology, and extent of collateral damage were
      evaluated using light and electron microscopy. RESULTS: Best ablation
      efficiencies were demonstrated with the ultrashort pulsed laser (1 micron/mJ),
      whereas maximum material removal per pulse was obtained with the Er:YAG laser (80
      microns/ pulse). Scanning electron microscopy showed cracking damage with both
      Ho:YSGG and Er:YAG. XeC1 and the ultrashort pulse system left tissue surfaces
      free of cracks or thermal damage. CONCLUSION: With its minimal acoustical and
      mechanical impact, high efficiency, and negligible collateral damage, the
      ultrashort pulse laser at 3 J/cm2 was found to be the optimal laser system for
      nail ablation.

PMID- 9261797
TI  - Subsurface morphologic changes of ND:YAG laser-etched enamel.
AB  - BACKGROUND AND OBJECTIVE: Etching the enamel surface with a Nd:YAG dental laser
      produces impact craters with cavities, micropores, and microfissures. This in
      vitro SEM study examined laser-etched enamel to determine the pattern and extent
      of subsurface changes. STUDY DESIGN/MATERIALS AND METHODS: The facial surface of
      10 maxillary central incisor teeth were coated with a black initiator and laser
      etched with a pulsed Nd:YAG laser (1.06 lambda, 75 mJ, 15 Hz, 320 microns fiber,
      94 J/cm2 fluence). The facial surface of five teeth were plastic-embedded under a
      low vacuum, then demineralized in 10% formic acid. The other teeth were split
      incisoapically. All samples were prepared for SEM. RESULTS: Examination of the
      plastic impressions showed a delicate interlacing pattern of thin partitions and
      small knob-like expansions. Examination of the split teeth showed the penetration
      of microfissures into the enamel estimated at 10 microns. CONCLUSION: These
      subsurface alterations may provide space for the infiltration and mechanical
      retention of dental resin.

PMID- 9261798
TI  - Intrarenal use of the holmium laser.
AB  - BACKGROUND AND OBJECTIVE: We investigated the safety, effectiveness, and
      techniques of the holmium (Ho:YAG) laser intrarenally. Data are presented on 52
      patients who were treated with the Ho:YAG laser intrarenally for urinary calculi
      or neoplasms. STUDY DESIGN/MATERIALS AND METHODS: The Ho:YAG laser has a
      wavelength of 2,100 nm, which is delivered in pulsed fashion via a small flexible
      quartz fiber (365 microns), which is placed through a working channel (> 2.2 Fr)
      of a small diameter endoscope. RESULTS: Sixty-three intrarenal procedures were
      performed with the Ho:YAG laser for calculi and neoplasms. Twenty-four procedures
      were performed for intrarenal neoplasms. Average total energy used in these
      patients was 2.61 kilojoules (kJ) with a maximum of 15.28 kJ. Thirty-nine
      procedures were performed for intrarenal calculi; 7/39 procedures were approached
      percutaneously. Average total energy in stone patients was 5.41 kJ with a maximum
      of 37.77 kJ. CONCLUSION: The Ho:YAG laser can be used safely and effectively to
      treat intrarenal calculi or neoplasms. All types of calculi were fragmented and
      all patients with intrarenal tumor were treated successfully. There were no
      vascular or renal injuries and there was no evidence of renal loss. No intrarenal
      strictures were seen on follow-up. The Ho:YAG laser energy can be delivered
      through a small flexible quartz fiber passed through a small diameter endoscope.
      The techniques and applications of the Ho:YAG laser make it well suited for
      urologic application.

PMID- 9261799
TI  - Treatment of a nonresponding port-wine stain with a new pulsed light source
      (PhotoDerm VL).
AB  - BACKGROUND AND OBJECTIVE: The pulsed dye laser is effective and safe in the
      treatment of port-wine stains. It is the laser of choice for port-wine stains and
      initial superficial hemangiomas in children. For the treatment of darker port
      wine stains in adults that have not responded to pulsed dye laser treatment,
      excellent results can be achieved using the PhotoDerm VL, a new technology based
      upon the emission of wide band, noncoherent intense pulsed light. STUDY
      DESIGN/PATIENT AND METHODS: Our report presents a patient with a facial port-wine
      stain that hardly responded to previous pulsed dye laser therapy. After the first
      ineffective treatment trial, the patient refused further dye laser applications.
      An intense pulsed light source (Photoderm VL) was applied instead. RESULTS: The
      lesion responded well after the first treatment session and was completely
      resolved after four treatments with the PhotoDerm VL. CONCLUSIONS: The new
      intense pulsed light source Photoderm VL seems to be a promising treatment
      alternative for the therapy of otherwise nonresponding port-wine stains due to
      its special technical features.

PMID- 9261800
TI  - Voltage-activated intracellular calcium transients in thalamic relay cells and
      interneurons.
AB  - The dynamics of intracellular calcium concentration ([Ca2+]i) following
      activation of low voltage-activated (LVA) and high voltage-activated (HVA) Ca2+
      currents were studied in identified relay neurons and interneurons of the rat
      dorsal lateral geniculate nucleus (LGNd) in situ using Ca2+ imaging and patch
      clamp techniques. In relay neurons, [Ca2+]i transients associated with the LVA
      Ca2+ current showed a fairly homogeneous somatodendritic distribution, whereas
      HVA transients significantly decreased to 65% of the somatic value at 60 microns
      dendritic distance. In interneurons, LVA transients significantly increased to
      239% of the somatic value at 60 microns dendritic distance, whereas HVA
      transients were not significantly different in the soma and dendrites. These
      results indicate differences in [Ca2+]i dynamics, which may reflect a
      heterogeneous distribution of Ca2+ channels contributing to subcellular
      compartmentation in the two types of thalamic neurons.

PMID- 9261801
TI  - Fast visual evoked potential input into human area V5.
AB  - Studies of the human visual cortex have demonstrated that an area for motion
      processing (V5) is located in the lateral occipito-temporal cortex. To study the
      timing of arrival of signals in V5 we recorded multi-channel visual evoked
      potentials (VEPs) to checkerboard stimuli. We then applied dipole source analysis
      which was computed on a grand average of 10 subjects, and on five individual
      subjects, respectively. We demonstrate an early VEP component with onset before
      30 ms and with a peak around 45 ms, located in the vicinity of V5. This early
      component was independent of a second activity, which started around 50 ms and
      peaked around 70 ms, and was located within the striate cortex (V1). These
      results provide further evidence for a very fast input to V5 before activation of
      V1.

PMID- 9261802
TI  - Acute ischemic vulnerability of PKA in the dendritic subfields of the hippocampus
      CA1.
AB  - Alterations of [3H]cyclic AMP (cAMP) binding, an indicator of the binding
      activity of particulate cyclic AMP-dependent protein kinase (PKA), were examined
      after 15 and 30 min of ischemia in the gerbil brain. Severe hemispheric cerebral
      ischemia was induced by occluding the right common carotid artery. Significant
      reductions in cAMP binding were noted only in the dendritic subfields of the
      hippocampus CA1 such as the strata oriens, radiatum and lacunosum-moleculare, on
      the ischemic side after 15 min of ischemia. After 30 min ischemia cAMP binding
      was significantly decreased not only in each dendritic subfield of the
      hippocampus CA1, but also in the layer of pyramidal cell bodies (stratum
      pyramidale) on the occluded side; other brain regions such as the hippocampus
      CA3, dentate gyrus and cerebral cortices revealed no significant changes in cAMP
      binding. These findings suggest that derangement of PKA may begin in the
      dendritic subfields of the hippocampus CA1 after as little as 15 min of severe
      ischemia, and proceed centrally to the neuronal cell bodies of the hippocampus
      CA1.

PMID- 9261803
TI  - Fear decrease in transgenic mice overexpressing bcl-2 in neurons.
AB  - Neuronal destruction in the amygdala, hypothalamus and cerebellum provokes a
      diminution in anxiety and neophobia. In transgenic mice that express the human
      bcl-2 gene under the control of neuron specific enolase promotor (Hu-bcl-2), BCL
      2 overexpression reduces the naturally occurring neuronal death, producing an
      increase of the number of neurons and brain size. Since BCL-2 over-expression has
      been observed in different parts of the brain and especially in the amygdaloid
      nuclei, the hypothalamus and the cerebellum, we studied the fear-related behavior
      of these transgenic mice. Hu-bcl-2 transgenic mice showed a decrease in anxiety
      and neophobia, indicating that, for this particular behavior, supernumerary
      neurons elicit the same modification as that observed after neuronal destruction.

PMID- 9261804
TI  - Alpha 5 subunit forms functional alpha 3 beta 4 alpha 5 nAChRs in transfected
      human cells.
AB  - nAChRs heterologously expressed in human cells after transient transfection with
      alpha 3 beta 4 alpha 5 or alpha 3 beta 4 subunit cDNAs exhibited similar
      sensitivities to antagonists and comparable functional channel profiles. However,
      the sum of two Hill equations was required for best fitting the ACh dose-current
      response curves after co-expression of alpha 5, alpha 3 and beta 4 subunits. One
      component was comparable to that obtained in alpha 3 beta 4-transfected cells,
      while the additional component, putatively attributed to an alpha 3 beta 4 alpha
      5 nAChR population, showed a Hill coefficient > 2 and a nine-fold greater half
      maximal ACh concentration (EC50). These results suggest that the alpha 5 subunit
      participates in the assembly of alpha 3 beta 4 alpha 5 nAChRs complexes in human
      cells, adding a new member to the family of neuronal nicotinic receptors.

PMID- 9261806
TI  - Co-localization of glycine and calbindin D-28k in the vestibular ganglion of the
      rat.
AB  - Bipolar neurons of the vestibular ganglion (VG) are biochemically heterogeneous.
      The calcium-binding protein calbindin D-28k (Calb) is present only in a subset of
      particularly large neurons, and the amino acid glycine (Gly) has been
      immunocytochemically detected in a group of similarly sized cells. The close
      correspondence in size and number of cells in these two subgroups suggests that
      the Calb- and Gly-positive populations may be identical. In order to test this
      hypothesis, we performed direct and indirect double-labeling for Calb and Gly in
      the VG of the rat. The results confirm the existence of a distinct subpopulation
      of Calb-immunoreactive neurons, consisting of the largest cells in the VG. In
      contrast, the vast majority of neurons in the VG display some degree of Gly
      immunoreactivity, which gradually decreases from intense to almost unlabeled.
      Direct evidence is provided that the fraction of cells most heavily labeled by
      Gly antibodies is not identical with the Calb-positive subpopulation. Although
      some correlation between soma diameter and labeling intensity exists, Gly
      immunoreactivity is clearly not restricted to large neurons. The findings imply
      that the functional mechanisms in which Gly is potentially involved may be shared
      by a large spectrum of primary vestibular afferents with a broad range of
      physiological properties.

PMID- 9261805
TI  - Cocaine self-administration alters brain NADH dehydrogenase mRNA levels.
AB  - Using differential display PCR, we identified a cDNA whose expression is altered
      in several brain regions in rats self-administering cocaine. The cDNA sequence
      corresponds to bases 13687-13723 of the rat NADH dehydrogenase subunit 6 gene.
      Northern analysis indicated a 26% decrease in nucleus accumbens, a 305% increase
      in the ventral midbrain and no changes in the caudate putamen mRNA levels;
      changes were also noted in the hypothalamus and cerebellum. This is the first
      demonstration of an effect of cocaine self-administration on mitochondrial gene
      expression and suggests that regional metabolic changes elicited by cocaine may
      be relevant to and involved in its reinforcing properties.

PMID- 9261807
TI  - Neuropsychological changes in subjects at risk of inheriting Alzheimer's disease.
AB  - Subjects from four Mexican families at risk of inheriting Alzheimer's disease
      (AD) were studied using a complete neuropsychological battery. These tests were
      repeated and compared 1 year later. Some of the experimental subjects belong to
      an international protocol on molecular chromosomal study. A control group matched
      in age and schooling was included. The subjects at risk underwent a complete
      physical, neurological and neuropsychological assessment. A neuropsychological
      battery of cognitive domains designed for the the study of dementia syndromes was
      administered to all subjects. Six of the subjects showed abnormal performance in
      cognitive functions, memory, visuospatial functions or language which persisted 1
      year later. The present work describes the initial findings of a long-term
      prospective study aimed at delineating the neuropsychological profile of subjects
      at risk and to validate subtle abnormalities which in some cases could be the
      incipient changes of AD.

PMID- 9261808
TI  - Expression cloning of rat cerebellar adenosine A1 receptor by coupling to Kir
      channels.
AB  - G protein activation of inwardly rectifying K+ (Kir) channels by heptahelical
      receptors is an important signaling motif in slow synaptic transmission in the
      mammalian brain. To isolate candidate receptors responsive to the purine
      nucleoside adenosine, a cerebellar cDNA library was constructed in the vector
      pSGEM and transcripts were injected into Xenopus Laevis oocytes co-expressing
      Kir3.1 and/or Kir3.2 subunits. Stepwise fractionation and functional
      characterization of the library using two-electrode voltage clamp measurements
      resulted in the identification of a single unique cDNA clone with an open reading
      frame of 326 amino acids. The pharmacological properties as determined from the
      responses to cyclopentyl-adenosine (CPA, EC50 = 7 nM) and CGS21680 (EC50 = 2.6
      microM) were typical of adenosine A1 receptors. The differential receptor
      coupling to heteromeric Kir channels composed of Kir3.1-4 subunits provides a
      useful technique to isolate novel heptahelical receptors.

PMID- 9261809
TI  - Extra-junctional localization of glutamate transporter EAAT4 at excitatory
      Purkinje cell synapses.
AB  - We used silver-enhanced immunogold electron microscopy to reveal synaptic
      localization of the glutamate transporter EAAT4 in mouse cerebellar Purkinje
      cells (PCs). Gold-silver particles representing the EAAT4 were densely localized
      on extra-junctional membrane, but not on junctional membrane of PC spines in
      contact with parallel fiber or climbing fiber terminals. No particle
      accumulations were observed at inhibitory synapses formed on cell body and
      dendritic shafts of PCs. Therefore, the EAAT4 is selectively targeted to the
      extra-junctional site of excitatory PC synapses. The finding suggests that the
      EAAT4 transports glutamate or its related amino acids from outside the synaptic
      cleft, which would facilitate glutamate diffusion from the synaptic cleft to the
      extrasynaptic space and restrict glutamate spillover to adjacent synapses.

PMID- 9261810
TI  - Orthovanadate induces cell death in rat dentate gyrus primary culture.
AB  - The aim of this study was to define the effects of a potent inhibitor of tyrosine
      phosphatases, sodium orthovanadate (0.1-100 microM for up to 48 h), on dentate
      gyrus cells (DGC) in culture. Treatment with 100 microM orthovanadate evoked a
      delayed form of cell death. To examine the possible involvement of apoptosis in
      orthovanadate-induced cell death, biochemical and morphological alterations were
      compared with those of necrotic death induced by sodium azide. Phase-contrast
      microscopy and nuclear condensation analysis showed that orthovanadate and azide
      each evoked cell death by distinct pathways. TUNEL assay was positive in both
      cases. Application of a protein synthesis inhibitor, cycloheximide, did not
      prevent cytotoxicity caused by either orthovanadate or azide and potentiated the
      effects of vanadate. We conclude that orthovanadate-induced death of DGC bears
      features of apoptosis.

PMID- 9261812
TI  - Nucleus accumbens lesions impair context, but not cue, conditioning in rats.
AB  - Previous work has provided evidence of a role for the hippocampal formation in
      contextual as opposed to cue conditioning. Similar deficits have been observed
      after transection of the fimbria/fornix, part of which consists of the
      hippocampal-nucleus accumbens (N.Acc) connection arising from both the dorsal and
      ventral subiculum. By means of electrolytic lesions of the N.Acc, we showed that
      the subiculo-accumbens projection appears to participate in aversive conditioning
      to context, but not to a cue (tone). Freezing, measured as an index of learning,
      in the experimental context was greatly reduced in animals with lesions of the
      N.Acc, as compared with sham-operated controls. No difference was found in
      freezing to a distinct tone. These data lend further support to the notion that
      the N.Acc is an important interface between limbic structures and motor output.

PMID- 9261811
TI  - Enkephalinergic nerve terminals target inhibitory interneurons in the rat
      hippocampus.
AB  - Using correlated light and electron microscopic preembedding enkephalin
      immunocytochemistry combined with post-embedding GABA immunogold staining, we
      found morphological evidence of a direct connection between the enkephalinergic
      and GABAergic systems in the rat hippocampus. Enkephalin-immunoreactive boutons
      were found to be presynaptic to GABA-immunoreactive postsynaptic profiles,
      establishing type 2 symmetrical synapses on GABA-positive cell bodies and
      dendritic shafts in strata radiatum and lacunosum moleculare of the CA1 region.
      Thirty-six percent of all studied postsynaptic targets (n = 40) were non
      pyramidal, including all somatic (n = 7) and 47% of the dendritic (n = 13)
      postsynaptic targets. The remaining 64% consisted of pyramidal dendritic shafts
      and spines. These results support previous physiological experiments suggesting
      that the opioidergic system takes part in disinhibitory processes in the
      hippocampal formation.

PMID- 9261813
TI  - Transient forebrain ischemia in the adult gerbil is associated with a complex c
      Jun response.
AB  - C-Jun expression in the hippocampus of gerbils subjected to 5 min of transient
      forebrain ischemia was examined with immunohistochemistry and western blotting
      using two c-Jun antibodies raised against two different amino acid sequences.
      Both c-Jun antibodies showed increased immunoreactivity at 6 and 12 h
      postischemia in the stratum pyramidale of CA3 and granule cell layer of the
      dentate gyrus. No immunostaining was detected in CA1 up to the 7th day. Western
      blots showed increased c-Jun immunoreactivity at 6 and 12 h. However, the
      antibody c-Jun (AB-1) detected a single band at about p39 in normal and post
      ischemic states, whereas the antibody c-Jun/AP-1 (N) recognized a band at about
      p39 in normal and post-ischemic gerbils, and a p62 phosphorylated double-band at
      6 and 12 h following ischemia. In addition, increased c-Jun N-terminal kinase-1
      (JNK-1) expression was observed on western blots at 6 and 12 h postischemia.
      These results suggest that different c-Jun-related responses, some of which
      probably indicate post-translational changes of the c-Jun protein, occur in the
      hippocampus of the gerbil following transient forebrain ischemia.

PMID- 9261814
TI  - Desensitization of spinal 5-HT1A receptors to 8-OH-DPAT: an in vivo spinal reflex
      study.
AB  - Serotonergic influence on spinal monosynaptic transmission and the
      desensitization of spinal 5-HT1A receptors following a single pretreatment with a
      5-HT1A ligand were examined in vivo in acutely spinalized adult rats.
      Administration of a selective 5-HT1A agonist, 8-OH-DPAT (0.1 mg kg-1)
      significantly depressed the monosynaptic mass reflex (MMR) amplitude, which was
      prevented effectively by S(-)-propranolol, a 5-HT1A antagonist. The inhibitory
      effect of 8-OH-DPAT on MMR amplitude was significantly attenuated with a single
      dose of 8-OH-DPAT (1 mg kg-1, s.c.) administered 24 h before the experiments,
      indicating a marked desensitization of spinal 5-HT1A receptors. Desensitization
      of 5-HT1A receptors could be reversed by treatment of spiperone (1 mg kg-1, i.p.)
      3 h before 8-OH-DPAT pretreatment. These results demonstrate that 5-HT1A receptor
      functionally modulates the spinal motor output and confirms the ability of 8-OH
      DPAT to desensitize presynaptic 5-HT1A receptors as observed for the first time
      in rat spinal cord.

PMID- 9261815
TI  - GABAergic neurons with AMPA GluR1 and GluR2/3 immunoreactivity in the rat striate
      cortex.
AB  - The co-localization of GABA with AMPA receptor subunits GluR1 or GluR2/3 was
      analysed in the striate cortex of adult rats by post-embedding
      immunocytochemistry in semithin sections. Adjacent 1 micron semithin sections of
      four brains were alternately incubated with specific antibodies against GABA and
      the GluR1 and GluR2/3 subunits. The post-embedding immunocytochemistry showed
      that 38% of GABAergic neurons contained the GluR1 subunit and 10% contained the
      GluR2/3 subunits. Previous work has shown GluR1 immunoreactivity in non-pyramidal
      neurons and GluR2/3 immunoreactivity in pyramidal neurons. However, this study is
      the first to demonstrate that there are GABAergic neurons co-localized with
      GluR2/3 AMPA subunits. Additionally, this study provides quantitative estimations
      of the laminar distribution of GABAergic and non-GABAergic cells containing the
      AMPA GluR1 and GluR2/3 subunits.

PMID- 9261816
TI  - Synaptic plasticity in olfactory memory formation in female mice.
AB  - Female mice develop a long-lasting olfactory recognition memory of a partner male
      at the first relay in the vomeronasal system. In this study the synaptic
      plasticity relevant to this phenomenon was examined at reciprocal dendrodendritic
      synapses in the accessory olfactory bulb of female mice by electron microscopy.
      The size of asymmetrical excitatory synapses (mitral/tufted to granule cells) of
      the reciprocal synapses was significantly larger in the group of female mice
      which were subjected to a treatment intended to induce olfactory memory formation
      than in the control group. It is suggested that olfactory memory formation is
      associated with a conformational change at the level of synaptic structure of the
      accessory olfactory bulb.

PMID- 9261817
TI  - Altered synaptic plasticity in hippocampal CA1 area of apolipoprotein E deficient
      mice.
AB  - In mice with a homozygous or heterozygous deficiency for ApoE as well as in wild
      type animals we established synaptic responsiveness in the hippocampal CA1 area
      following stimulation of the Schaffer/commissural fibers. The maximal population
      spike amplitude was significantly larger in wild-type animals than in mice
      lacking the ApoE gene, whereas the facilitation in population spike amplitude
      after paired pulse stimulation was most pronounced in homozygous mutant mice.
      Primed burst stimulation induced a lasting increase in population spike amplitude
      of all three groups. Apart from a more pronounced initial potentiation in the
      homozygous mutants, primed burst potentiation was comparable in all groups.
      Subsequent theta burst stimulation resulted in a long-term enhanced synaptic
      responsiveness which was impaired in heterozygous animals. The data show that
      both homo- and heterozygous ApoE mutant mice display altered synaptic plasticity
      in the hippocampal CA1 area.

PMID- 9261818
TI  - Attention-related modulation of activity in primary and secondary auditory
      cortex.
AB  - We investigated the effects of auditory attention on brain activity using
      functional magnetic resonance imaging. Subjects listened to three word lists,
      three times each, and were instructed to count the number of times they heard a
      target word during two of these presentations. For the third, they listened to
      the words without counting. All subjects showed significant areas of activation
      in auditory cortex during the listening conditions compared to rest. There was
      significantly more activation and a larger area of activation, particularly in
      association cortex, in the left temporal lobe during counting of targets compared
      to the no-target conditions, with a similar trend in the right hemisphere. These
      results provide evidence of an attention-related enhancement of both activation
      magnitude and extent in auditory cortex.

PMID- 9261819
TI  - The influence of the subsurface cisterna on the electrical properties of the
      outer hair cell.
AB  - A distributed-parameter computational model of the outer hair cell was used to
      predict the potentials resulting from current injection. A good fit was found to
      the length-dependent whole cell conductance and capacitance. The fit required the
      presence of the subsurface cisterna and a low (0.001 mS/cm2) specific
      conductivity for the plasma membrane of the lateral wall. The lateral wall could
      not be space clamped as significant longitudinal currents pass through the
      extracisternal space vs the axial core. A reduction in the width of the
      extracisternal space decreased the whole-cell conductance and capacitance.
      Position-dependent phase shifts were noted during injection of sinusoidal
      currents (0.001575 rad/micron). These predictions support a role for
      extracisternal longitudinal potential gradients in experimentally observed non
      linear capacitance and electromotility.

PMID- 9261820
TI  - Effects of repeated amphetamine treatment on the locomotor activity of the
      dopamine D1A-deficient mouse.
AB  - The role of dopamine D1A receptors in mediating amphetamine-induced sensitization
      was investigated using the D1A-deficient mouse. During the drug pre-exposure
      phase, D1A-deficient and control mice were injected for five consecutive days
      with saline or amphetamine (2 mg/kg, i.p.). Locomotor activity was measured on
      the first and fifth pre-exposure day. After three abstinence days, mice were
      given either amphetamine or saline and locomotor activity was again assessed.
      Mice were then sacrificed and protein kinase A (PKA) activity was measured. In
      contrast to control mice, D1A-deficient mice did not show a progressive increase
      in locomotor activity across days. Importantly, both control and mutant mice did
      exhibit behavioral sensitization, because mice pre-exposed and tested with
      amphetamine were more active than mice acutely tested with the drug. Even so, the
      amphetamine-induced locomotor activity of the mutant mice was significantly
      reduced when compared with similarly treated control mice, indicating that the
      sensitized response was less pronounced in the D1A-deficient mouse. PKA activity
      also varied depending on genotype, since amphetamine decreased PKA activity in
      control but not D1A-deficient mice.

PMID- 9261821
TI  - Aromatase cytochrome P450 and 5 alpha-reductase in the amygdala and cortex of
      perinatal rats.
AB  - The major androgen metabolizing enzymes, aromatase cytochrome P450 and 5 alpha
      reductase play critical role(s) in the development of sexually dimorphic brain
      structures, the modulation of neuroendocrine function(s) and the regulation of
      sexual and non-sexual behaviors. Using established assays, we detected 5 alpha
      reductase and aromatase enzymatic activities in amygdala and frontal cortical
      tissue from male and female rats during the perinatal interval (from gestational
      day (GD) 19 to postnatal day (PND) 6). The present findings indicate that 5 alpha
      reductase and aromatase rates in the cortex display different enzyme profiles,
      while in the amygdala tissue site a similar pattern is seen for both enzymes
      during perinatal development. In general, there was a lack of sex differences in
      the enzymatic rates. The importance these enzyme systems play in generating
      androgen (and progesterone) steroid metabolites which influence neural
      development and function are discussed.

PMID- 9261822
TI  - Mapping transcranial magnetic stimulation (TMS) fields in vivo with MRI.
AB  - Transcranial magnetic stimulation (TMS) is a non-invasive technique for
      investigating brain function that uses pulsed magnetic fields created by special
      coils to induce localized neuronal depolarization. Despite the technique's
      expanding application, the exact magnetic field produced by TMS coils have never
      been directly measured in human subjects. Using a standard 1.5T MR scanner and
      TMS coils constructed from non magnetic materials, we have obtained 3D maps of
      the magnetic field created by TMS coils in human volunteers. Further, we mapped
      the combined field of two coils and demonstrated that combinations of coils might
      be used to focus the magnetic field to achieve improved stimulation patterns and,
      perhaps, reach areas out of reach of single coils.

PMID- 9261823
TI  - Voltage dependent switch in the activity mode of the K+ channel in presynaptic
      nerve terminals.
AB  - The bursting K+ channel is the most common channel in fused Torpedo presynaptic
      nerve terminals. It possesses the property of 'statistical memory', demonstrated
      by non-random probability of channel opening. We examined the voltage dependence
      of the statistical memory and report that removal of channel inactivation by
      hyperpolarization abolishes it. Addition of the potassium channel blocker 4
      aminopyridine to the bath solution led to disappearance of statistical memory,
      while raising extracellular potassium concentration had the opposite effect.
      Another common channel at Torpedo nerve terminals which is a non-selective
      channel did not exhibit statistical memory. We conclude that statistical memory
      is a channel-specific phenomenon and speculate regarding its possible role in
      cellular and network properties of the nervous system.

PMID- 9261824
TI  - Association between a delta opioid receptor gene polymorphism and heroin
      dependence in man.
AB  - Two allelic variants of the delta opioid receptor gene, distinguished by a single
      base exchange T to C in codon 307 of the translated region, were detected in
      humans. The amino acid sequence was thereby not changed. The resulting C and T
      alleles combined to give the three genotypes CC, CT and TT. Allele C was more
      frequent in a sample of 103 German Caucasian heroin addicts (53.4%) than in a
      control group (39.1%, n = 115). The proportion of CC homozygotes was much greater
      among the drug-dependent subjects (26.2%) than in controls (9.6%). Although the
      reasons for this association remain to be explained, our results argue for a
      participation of the delta type of opioid receptors in the pathophysiology of
      heroin dependence.

PMID- 9261825
TI  - Olfactory cues from an oxytocin-injected male rat can reduce energy loss in its
      cagemates.
AB  - Rats can recognize the odor of a stressed conspecific and react with stress
      themselves. Stress mobilizes energy, causing increased core temperatures and
      energy loss by radiation from the naked tail. Oxytocin administered in high doses
      (1 mg/kg, s.c.) reduces a rat's tail skin temperature and thereby the radiated
      energy loss. While administration of this high dose of oxytocin induces sedation
      low doses induce anxiolysis. This study demonstrates that the cagemates of an
      oxytocin-treated (1 mg/kg s.c.) rat, which themselves have not received any
      oxytocin-treatment, show energy conservation, apparent as reduced tail skin
      temperature. This effect was blocked by olfactory impairment. The temperature
      reduction in the cagemates probably reflects an oxytocin-mediated olfactorily
      activated stress inhibitory mechanism.

PMID- 9261826
TI  - Evidence for asynchronous development of sleep in cortical areas.
AB  - We have recorded from extrastriate area V4 in monkeys performing a visual search
      task. When animals became tired or drowsy, responses to visual stimulation were
      often reduced or even completely blocked, and background activity changed to the
      burst-pause pattern typically seen in sleep. In spite of such neuronal sleep
      observed in V4, animals continued to perform the visual task, indicating that at
      least the primary visual cortex was still working. This observation shows that
      sleep does not develop simultaneously in all cortical areas but may affect some
      areas earlier than others. In particular conditions, local sleep of certain areas
      may be a stable and long-lasting phenomenon.

PMID- 9261828
TI  - (-)-OSU 6162 inhibits levodopa-induced dyskinesias in a monkey model of
      Parkinson's disease.
AB  - We have studied the effects of two D2 dopamine receptor-selective compounds, (-)
      OSU 6162 and raclopride, on levodopa-induced dyskinesias in 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP)-lesioned common marmosets (Callithrix jacchus).
      Three monkeys developed a severe parkinsonian syndrome following administration
      of MPTP. In response to daily levodopa treatment the animals developed
      reproducible and idiosyncratic peak-dose dyskinesias. Pretreatment with (-)-OSU
      6162 and raclopride, in doses increased by multiples of three, both dose
      dependently relieved the levodopa-induced dyskinesias. However, in contrast to
      when raclopride pretreatment was given, (-)-OSU 6162 pretreatment did not induce
      akinesia. Our investigation suggests that (-)-OSU 6162 may be useful an an
      adjuvant treatment to levodopa in advanced Parkinson's disease to selectively
      combat levodopa-induced dyskinesias without affecting the antiparkinsonian
      response.

PMID- 9261829
TI  - Pre-attentive categorization of sounds by timbre as revealed by event-related
      potentials.
AB  - Infrequent (10%) pure tones were randomly presented among nine different missing
      fundamental tones having the same pitch (10% each) to subjects playing a computer
      game. MMN (an index of pre-attentive change detection) was elicited by timbre
      deviant pure tones with 150 and 500 ms stimulus duration. This suggests that the
      spectral component of timbre is pre-attentively determined from relatively short
      (150 ms) acoustic samples. Previous research established that resolving the pitch
      of the same missing-fundamental tones requires longer (> 150 ms) sounds.
      Consequently, timbre and pitch are probably determined by separate neural
      processes. The present results also demonstrate pre-attentive categorization of
      sounds based on timbre as MMN could only be elicited by the pure tones if their
      timbre was contrasted with the combined group of the nine standard sounds of
      qualitatively similar rich timbre.

PMID- 9261827
TI  - mGluR modulation of post-traumatic neuronal death: role of NMDA receptors.
AB  - The potential interaction between group I metabotropic glutamate receptors
      (mGluR) and NMDA receptors in mediating of post-traumatic neuronal death was
      studied using an in vitro trauma model. Treatment with group I mGluR antagonists
      provided significant neuroprotection either in the presence or absence of an NMDA
      receptor antagonist. In contrast, treatment with a group I mGluR agonist alone
      significantly exacerbated injury; this exacerbation was significantly, but
      incompletely, reduced in the presence of an NMDA receptor antagonist. These
      findings are consistent with the conclusion that the effects of group I mGluR
      activation on post-traumatic cell death are mediated only in part through NMDA
      receptor modulation and suggest that group I mGluR antagonists may have important
      therapeutic potential.

PMID- 9261830
TI  - Visually induced gamma-band responses to coherent and incoherent motion: a
      replication study.
AB  - The present study was based on earlier findings that the observation of a
      coherently moving long bar induced gamma-band activity in humans. The power in
      the EEG-gamma-band was reduced during the presentation of two incoherently moving
      short bars. The present study demonstrates the replicability of this cortical
      activity pattern and illustrates intersubjective variability in its topography.
      In addition, cortical alpha-activity was examined to test whether gamma-band
      activity might reflect changes in harmonics of alpha waves. Results indicate that
      induced gamma-band activity cannot be secondary to changes in the amplitude of
      alpha waves, since the latter would require both a similar time course of both
      frequency bands while stimuli are in motion and an identical topographical
      pattern. The present results suggest that oscillations in the gamma- and the
      alpha-bands are two different brain activities, with different functional
      implications.

PMID- 9261831
TI  - Activity of presumed dopamine neurons in the ventral tegmental area during heroin
      self-administration.
AB  - To assess the pattern of mesocorticolimbic dopamine (DA) activity associated with
      drug-seeking and drug-taking behavior, we monitored the firing rate of presumed
      DA neurons in the ventral tegmental area of trained rats during i.v. heroin self
      administration (SA). Relative to a slow and irregular basal activity, the first
      SA of each session was preceded by a phasic increase and followed by a more
      persistent increase in discharge rate that peaked approximately 15-20 min later
      at the time of the second SA. All subsequent SAs were associated with a biphasic
      neuronal change: a transient decrease followed by a gradual increase that peaked
      just before the next SA. Our results support mesocorticolimbic DA activation in
      heroin-seeking behavior but suggest a transient inhibition of DA activity
      correlated with heroin reward.

PMID- 9261832
TI  - Descending pathway from the central pattern generator of vomiting.
AB  - The central pattern generator (CPG) for vomiting has been postulated to consist
      of non-respiratory neurons in the reticular area dorsomedial to the retrofacial
      nucleus. CPG neurons are known to produce vomiting activity patterns similar to
      respiratory spinal motoneurons and premotoneurons in the caudal part of the
      ventral respiratory group (cVRG). This study was performed to reveal direct
      connections between CPG neurons and cVRG neurons in dogs. Twenty-seven non
      respiratory neurons were identified as CPG neurons based on their responses to
      vagal stimulation and their firing patterns of vomiting. Nine of these 27 neurons
      antidromically responded to cVRG stimulation. These results suggest that the CPG
      directly drives respiratory premotor neurons in the cVRG to produce vomiting
      motions.

PMID- 9261833
TI  - Substrate transport and cocaine binding of human dopamine transporter is reduced
      by substitution of carboxyl tail with that of bovine dopamine transporter.
AB  - A chimeric dopamine transporter (DAT) cDNA encoding mutant human DAT (hDAT)
      protein in which the intracellular carboxyl-terminal tail is replaced by that of
      the bovine dopamine transporter (bDAT) was constructed. The chimeric hDAT cDNA
      was expressed in COS-7 cells, and [3H]dopamine and [3H]MPP+ uptake and [3H]CFT
      binding capacities were assessed. Substrate transport and ligand binding of bDAT
      were reduced by 32-43% as a result of substitution of the carboxyl tail in hDAT,
      suggesting that the functional characteristics of bDAT arise from differences in
      the carboxyl tail between human and bovine DAT. Thus, it appears that the
      sequences encoded within the carboxyl terminal of DAT would be one of the
      important determinants for its functions.

PMID- 9261834
TI  - Cellular basis of vestibular compensation: changes in intrinsic excitability of
      MVN neurones.
AB  - A systematic survey of the intrinsically generated in vitro discharge rates of
      rat medial vestibular nucleus (MVN) neurones was carried out in slices from
      normal animals and animals undergoing vestibular compensation over 48 h after
      unilateral labyrinthectomy (UL). Isolation of the individual MVN in vitro
      revealed that the tonic discharge rates of neurones in the rostral MVN
      ipsilateral to the lesion were not different from control 2 h post-UL, but
      increased significantly at 4 h post-UL and remained significantly higher until 24
      h post-UL. There were no significant changes in the in vitro discharge rates of
      MVN cells in the contralateral nucleus. The increase in excitability of the
      ipsilateral MVN cells after UL may be accounted for by a down-regulation of GABA
      receptors on these cells, following their sustained exposure to excessive
      commissural inhibition after labyrinthectomy. We suggest that the increased
      intrinsic excitability of the ipsilateral MVN cells is responsible for the
      restoration of the resting discharge in these cells after UL and the consequent
      recovery of static vestibular function.

PMID- 9261835
TI  - Roles of GABA, glutamate, acetylcholine and STN stimulation on thalamic VM in
      rats.
AB  - The effects of high frequency stimulation of the subthalamic nucleus (STN) and of
      iontophoretic application of different neurotransmitters on neuronal activities
      of the ventromedial thalamic nucleus (VM) were investigated in rats. GABA, when
      applied iontophoretically, inhibited VM neuronal activity while bicuculline, L
      glutamic acid and acetylcholine enhanced the firing rates of the same VM neurons.
      High frequency stimulation of the STN increased VM neuronal activity in a
      frequency-dependent manner, which could be blocked by MK801. These results
      suggest that GABAergic, cholinergic and glutamatergic input information converge
      in the same VM neurons and that an increase in the delivery of glutamatergic
      neurotransmitter activities in the VM is involved in the process of high
      frequency stimulation of the STN.

PMID- 9261836
TI  - OCAM reveals segregated mitral/tufted cell pathways in developing accessory
      olfactory bulb.
AB  - Two functional subsets of vomeronasal sensory neurons project their axons to two
      segregated zones in the accessory olfactory bulb (AOB). Using immunohistochemical
      methods with antibodies against the novel cell adhesion molecule OCAM, we provide
      evidence that the segregation of functional pathways is maintained at the level
      of mitral/tufted (M/T) cells of the mouse AOB and that this pattern emerges early
      in ontogeny. During embryonic and postnatal development OCAM was strongly
      expressed by M/T cells in the caudal zone of the AOB where OCAM-negative
      vomeronasal axons terminated. In contrast, rostral zone M/T cells innervated by
      OCAM-positive vomeronasal axons displayed no or faint OCAM immunoreactivity.
      Differential expression of OCAM in segregated M/T cell pathways suggests that
      OCAM may be involved in defining compartments of connectivity and setting up
      functional subdivisions in the developing AOB.

PMID- 9261837
TI  - Arylsulphatase A pseudodeficiency in vascular dementia and Alzheimer's disease.
AB  - The carrier rates of a genetic marker for arylsulphatase A pseudodeficiency (ASA
      PD) were determined in three series of patients with vascular dementia (VaD) or
      Alzheimer's disease (AD). In the first community-based sample, the 1524 + 95A-->G
      mutation, which is known to be associated with ASA-PD, was present in 35% of VaD
      cases and none of the AD cases. In a second sample of cases drawn from a Dementia
      Register, the mutation rates were 18% (VaD) and 16% (AD). Brain DNA from a post
      mortem sample revealed the ASA-PD mutation in 60% of VaD cases and 34% of AD
      cases. These rates are higher than previous studies of culturally similar
      populations and suggest that ASA-PD may be a risk factor for dementia.

PMID- 9261838
TI  - Parallel input to the hippocampal memory system through peri- and postrhinal
      cortices.
AB  - In the rat, the rhinal cortices consist of the perirhinal, postrhinal and
      entorhinal cortices. The perirhinal and postrhinal cortices, which serve as major
      input sources to the entorhinal cortex, receive functionally different types of
      information. In this study we looked at the projections from the perirhinal and
      postrhinal cortices to the different parts of the entorhinal cortices using an
      anterograde tracing technique. Our results show that the perirhinal cortex
      preferentially projects to the lateral entorhinal cortex, whereas the postrhinal
      cortex mainly sends fibers to the medial entorhinal cortex. Since the lateral and
      medial entorhinal cortices are differentially connected with the hippocampus, we
      suggest that functionally different types of information are processed in
      parallel in the hippocampal memory system.

PMID- 9261839
TI  - Endothelin-1 induced lesions of the frontoparietal cortex of the rat. A possible
      model of focal cortical ischemia.
AB  - Endothelin-1 (ET-1) was unilaterally applied onto the surface of the dorsal
      frontoparietal cortex of the rat. Cortical blood flow measurements using laser
      Doppler flowmetry demonstrated dose-dependent reductions of frontoparietal
      cortical blood flow. Histological analysis demonstrated dose-related lesions and
      the time course was followed using MRI. The lesions appear to be associated with
      a large penumbra area indicated by morphological characteristics. Thus, cortical
      surface exposure to ET-1 may produce graded lesions of the frontoparietal cortex
      related to local ischemia.

PMID- 9261840
TI  - Thiamine deficiency alters APP but not presenilin-1 immunoreactivity in
      vulnerable brain regions.
AB  - Presenilin-1 (PS-1) and amyloid precursor protein (APP) have been linked to the
      pathogenesis of Alzheimer's disease. While APP accumulation is well documented in
      several models of brain injury, the role of PS-1 levels in neurodegeneration, if
      any, remains to be elucidated. The current studies examined PS-1 and APP
      expression in brain following thiamine deficiency (TD), a nutritional model
      associated with impaired oxidation and selective neurodegeneration. TD did not
      alter PS-1 immunoreactivity in any region of rodent brain before or after cell
      loss. In contrast, APP immunoreactivity accumulated in swollen neurites within,
      or around lesions in rats, or in abnormal clusters in mice. Thus, alterations in
      APP but not PS-1 levels are involved in TD-induced neurodegeneration.

PMID- 9261841
TI  - Non-GABAergic effects of midazolam, diazepam and flumazenil on voltage-dependent
      ion currents in NG108-15 cells.
AB  - Non-gamma-Aminobutyric acid (GABA)-mediated effects of benzodiazepines (BZs) have
      not been widely investigated. However, there is significant evidence in the
      literature to suggest that several experimental and clinical observations are
      inconsistent with the commonly accepted GABAergic mechanisms of action for these
      drugs. The purpose of the present study was to explore electrophysiological
      effects of midazolam, diazepam and a specific BZ antagonist, flumazenil, using
      patch-clamp techniques in NG108-15 cells which do not express the GABAA receptor.
      Midazolam and diazepam decreased Na+, K+ and Ca2+ currents in a dose-related
      manner. Ca2+ currents were reduced more significantly by diazepam than by
      midazolam. Flumazenil showed no effects on voltage-dependent ion currents. GABA
      by itself showed neither effects on the membrane potential nor these ion
      currents. Midazolam and diazepam, but not flumazenil, exhibited effects on
      voltage-dependent ion currents in cultured neurons.

PMID- 9261842
TI  - Towards a human crystallin map. Two-dimensional gel electrophoresis and computer
      analysis of water-soluble crystallins from normal and cataractous human lenses.
AB  - This paper describes a first approach to establish a master data base of human
      lens crystallins obtained by computer analysis of standardized two-dimensional
      lenticular protein patterns. To facilitate the eventual identification of the
      spots, the major crystallins have been separated into alpha-, beta H-, beta L-
      and gamma-crystallin fractions by gel filtration. The authors encourage colleague
      investigators to collaborate in a common effort in order to arrive eventually at
      a two-dimensional gel data base of all lenticular proteins.

PMID- 9261843
TI  - Liquid chromatography/mass-spectrometric characterization of sphingomyelin and
      dihydrosphingomyelin of human lens membranes.
AB  - The identity of the major phospholipid component of human lens membrane extracts,
      previously referred to as the 'unknown phospholipid', was recently proposed to be
      4,5-dihydrosphingomyelin (DHS). Using high-performance liquid-chromatographic
      separation with atmospheric pressure chemical ionization and electrospray
      ionization mass-spectrometric detection, we report here the first identification
      of the molecular species of DHSs and sphingomyelins (SPMs) of the human eye lens.
      The most abundant molecular species were palmitic and tetracosenoic (24:1) DHSs,
      representing 57.8 and 23.3% of human lens DHSs, respectively. Lesser amounts of
      hexacosanoic, hexacosenoic, tetracosanoic, docosanoic, docosenoic, stearic,
      palmitoleic, myristic and other DHSs were found. The most abundant normal SPM
      molecular species in the human lens were similar to those of DHS. Palmitic SPM
      represented 53.9% of the uncorrected SPM peak areas, while tetracosenoic SPM
      represented 17.6% of the SPM in the human lens. The sphingolipids of the human
      lens were determined to be composed of 76.9% DHS species and 23.1% SPM species.
      Commercially available SPM was also found to contain significant amounts of DHS
      species.

PMID- 9261844
TI  - Some plasma constituents correlate with human cataract location and nuclear
      colour.
AB  - AIMS: To look for differences in levels of various plasma constituents between
      pair-matched controls and patients who had cataracts classified by location and
      appearance of lens opacity and nuclear colour in order to identify systemic risk
      factors. METHODS: One thousand patients were taken from the cataract waiting list
      of a specialist eye hospital. For each patient, a matched control of the same sex
      and half-decade of age but without cataract was taken from the patient-list of
      the family doctor of the patient; the control was the next alphabetically after
      the patient on the doctor's list. At an early morning visit to the homes of both
      patients and controls, fasting, a team of nurses performed venepunctures and
      collected information for a questionnaire. Eye examinations were performed by a
      team of ophthalmologists. RESULTS: Predominantly nuclear cataract was
      significantly associated with raised plasma alanine aminotransferase and
      bilirubin, posterior subcapsular cataract with increased calcium and urea,
      cuneiform with reduced potassium, mature/hypermature with raised potassium and
      reduced total carbon dioxide. The following were consistently significantly
      associated with all forms of cataract; diabetes and raised plasma glucose (not in
      non-diabetics), use of steroid medication, raised levels of cortisol (steroid
      users excluded), albumin, alkaline phosphatase, gamma-glutamyl transpeptidase,
      sodium and total protein and reduced levels of cholesterol and albumin/(total
      protein-albumin) ratio (an approximation for the albumin/globulin ratio). The
      multivariate analysis indicated that the most important non-specific
      cataractogenic effects were those of increased total protein, diabetes and use of
      steroid medication. CONCLUSION: This and other studies support, broadly, the
      conclusions that senile or age-related cataract is not merely caused by
      increasing age and also that various morphological types have different risk
      factors. The mechanisms underlying the biochemical associations with different
      patterns of lens opacification and the identification of the ultimate risk
      factors remain to be elucidated.

PMID- 9261845
TI  - Effects of different formulations of mitoxantrone (solutions, nanospheres,
      liposomes) on glaucoma surgery in rabbits.
AB  - Pharmacological blockade of fibroblastic proliferation after glaucoma filtration
      surgery by using antimitotic agents in different formulations (liposomes,
      nanospheres) is of great clinical interest. However, only limited comparative
      data are available on the effect of encapsulated drugs on intraocular pressure
      (IOP) after filtering surgery. Therefore we have studied the effect on IOP of
      liposomes, nanospheres and a solution of mitoxantrone (MTO), a well-known
      antimitotic, in rabbits before and after sclerectomy. MTO in solution form, as
      well as in a liposome formulation, improved the outcome of the surgery by
      reducing IOP when administered subconjunctivally just following surgery. This
      effect was similar to mitomycin-C application. In contrast, neither prior
      administration nor subconjunctival nanosphere injections induced a reduction in
      IOP. Liposome administration demonstrated no delayed action or promoting effect
      but reduced the occurrence of corneal opacity observed in groups treated with MTO
      in solution.

PMID- 9261847
TI  - Uniform symbols, abbreviations, and units in pediatric pulmonary function
      testing.

PMID- 9261846
TI  - Concomitant treatment with a 5-lipoxygenase inhibitor improves the anti
      inflammatory effect of the inhibition of nitric oxide synthase during the early
      phase of endotoxin-induced uveitis in the rabbit.
AB  - Nitric oxide (NO) synthase inhibitors, such as NG-nitro-L-arginine methyl ester
      (L-NAME), have been shown to attenuate endotoxin-induced uveitis (EIU) but they
      could increase leukocyte adhesion to the vascular endothelium. We hypothesize
      that a concomitant treatment with the 5-lipoxygenase inhibitor
      nordihydroguaiaretic acid (NDGA) in 50% dimethylsulfoxide (DMSO, a hydroxyl
      radical scavenger) could improve the anti-inflammatory activity of L-NAME. EIU
      was induced in albino rabbits by intravitreal injection of 100 ng
      lipopolysaccharide. Animals were treated with multiple intraperitoneal injections
      of 50% DMSO in phosphate-buffered saline (PBS), NDGA (10 mg/kg) in 50% DMSO, L
      NAME (50 mg/ kg) in PBS, or the combination NDGA+L-NAME. Uveitis was assessed by
      slit lamp examination, protein levels in aqueous humor, and myeloperoxidase (MPO)
      activity in the iris/ciliary body 6 h after induction. Nitrite, leukotriene B4
      (LTB4), prostaglandin E2 (PGE2), platelet-activating factor (PAF) and interleukin
      1 beta (IL-1 beta) levels in aqueous humor were also determined. NDGA or L-NAME
      alone did not show a significant reduction of uveitis intensity, although a
      significant decrease in MPO or in proteins was found, respectively. The
      combination NDGA+L-NAME significantly reduced the uveitis intensity, MPO in the
      iris/ciliary body, and the levels of nitrites, LTB4, PGE2, and PAF in aqueous
      humor. IL-1 beta levels were lower than the detection limit of the
      radioimmunoassay in all treatment groups. We conclude that concomitant treatment
      with NDGA in DMSO improves the anti-inflammatory activity of L-NAME during the
      early phase of EIU, suggesting that the inhibition of NO synthesis could enhance
      leukocyte infiltration and the release of oxygen free radicals.

PMID- 9261848
TI  - Comparative biochemistry of gestational and postnatal lung growth and development
      in the rat and human.
AB  - We compared the ontogeny of collagen (hydroxyproline), elastin (desmosine),
      soluble protein, and DNA in the lungs of rate and humans during gestation and
      postnatal life. In humans, lung weight/body weight ratios declined faster during
      gestation than postnatally, whereas in rats lung weight/body weight ratio
      declined little during gestation and then suddenly on the first day of life. Lung
      weight/body weight ratios may be lower than expected around term in humans, and
      prediction data are given to assess human pulmonary hypoplasia. Rats and humans
      differed in water content of their lungs, with rats showing a sharper decline
      during gestation. In the human lung, collagen and elastin made their appearance
      at an early stage of gestation; elastin. In particular, increased rapidly during
      gestation, suggesting a role in intrauterine alveolar formation. In the rat,
      elastin accumulation is primarily a postnatal event, as is alveolar formation.
      Hydroxyproline concentrations increased with conceptual age and continued to
      increase rapidly postnatally between 4 and 7 weeks in the rat, but slowed in the
      human after 60 weeks of conceptual age. Desmosine concentrations level off at the
      end of the study period in rats, while these are still increasing, although
      slowly, in humans. Overall lung growth, as assessed by weight, was linear in
      humans, but phases of lung growth were apparent in the rat, including one of
      minimal growth in the immediate postnatal period.

PMID- 9261849
TI  - Bronchopulmonary dysplasia of the premature baby: an immunohistochemical study.
AB  - Prematurely born infants who required assisted ventilation may develop chronic
      lung disease or bronchopulmonary dysplasia (BPD). The cells involved in the
      reparative process of the premature lung are not well defined. The repair of
      injured tissues is a highly standardized process and the most important cells are
      activated (modulated) fibroblasts (myofibroblasts). A key cytokine in controlling
      repair is transforming growth factor-beta (TGF-beta). To characterize the cells
      involved in the repair process of the premature lung, we employed
      immunocytochemical techniques and examined the lungs of 39 autopsied premature
      babies who had neonatal respiratory distress syndrome (RDS). All were treated in
      neonatal intensive care units and required mechanical ventilation and
      supplemental oxygen; all survived for at least 12 hours. Antibodies were employed
      against vimentin, alpha-smooth muscle (alpha-SM) actin, total muscle actin,
      desmin, MAC387, and TGF-beta. Our study indicates that myofibroblasts are
      normally present along terminal airways in the developing lung. These cells
      increase in number some days after lung injury, form bundles of cells encircling
      terminal air spaces, and acquire desmin contractile filaments shortly thereafter.
      Myofibroblasts do not lose their contractile filaments with time, suggesting a
      conversion to smooth muscle metaplasia. The proliferation and migration of such
      myofibroblasts at sites of lung injury is associated with the presence of TGF
      beta. These findings suggest that myofibroblasts play an important role in
      premature lung repair. They may point the way to experimental and clinical trials
      that will identify drugs antagonistic to TGF-beta (or other cytokines). Such
      antagonists may protect the neonates who are at high risk of developing BPD.

PMID- 9261850
TI  - Proteinase-free myeloperoxidase increases airway epithelial permeability in a
      whole trachea model.
AB  - In cystic fibrosis the bronchiectatic conducting airways have large numbers of
      neutrophils in their walls and in their luminal contents. The neutrophil's
      primary granule enzyme activities of elastase and peroxidase are increased in the
      sputum of these patients. It has been postulated that these enzymes--together or
      individually--act to damage the airway epithelium. However, only peroxidase
      activity has consistently correlated with the degree of structural and functional
      airway disease in these patients with leakage of plasma protein into the airway
      lumen (Regelmann et al., Pediatr Pulmonol, 1995; 19:1-9). The present study was
      designed to test whether human neutrophil-derived myeloperoxidase can
      independently produce bronchial epithelial damage without the presence of
      proteases, as measured by increased permeability of the airway epithelium. Human
      peripheral blood neutrophils were purified, their primary granules isolated, and
      their peroxidase purified using affinity and ion exchange column chromatography.
      Activity of the proteinase-free peroxidase was measured using a chromogenic
      substrate. The effect of this peroxidase on the permeability of excised rat
      tracheas was measured using radioactive and fluorescent-labeled non-ionic
      molecules of varying molecular weight. Rat tracheas exposed to 15 minute
      treatments with either 130 U of peroxidase or hydrogen peroxide (10(-5) M) did
      not show a significant increase in the permeability of the epithelium to
      [3H]inulin, [14C]sucrose, and fluorescein isothiocyanate dextran 20 compared with
      control tracheas. However, those tracheas exposed to 130 U peroxidase followed by
      10(-5) M hydrogen peroxide showed an increased permeability to each of the three
      test solutes. We conclude that proteinase-free myeloperoxidase, in the presence
      of non-toxic concentrations of its substrates, hydrogen peroxide and halide,
      produced increases in permeability to non-ionic molecules in the rat trachea
      within 15 minutes.

PMID- 9261851
TI  - Nasopharyngeal eosinophil cationic protein in bronchiolitis: relation to viral
      findings and subsequent wheezing.
AB  - A prospective 4-month follow-up of children hospitalized with bronchiolitis
      revealed that high concentrations of eosinophil cationic protein (ECP) in
      nasopharyngeal aspirates (NPA) are predictive of wheezing after bronchiolitis. In
      the 29 patients who received no anti-inflammatory therapy the median
      concentration of NPA ECP was 882 ng/g in those with physician-diagnosed wheezing
      (P = 0.02). The NPA ECP concentration of the whole study group of 88 children
      with and without subsequent hospital admissions for wheezing were 531 and 299
      ng/g, respectively (P = 0.02). At entry the children with negative viral findings
      had significantly higher concentrations of respiratory tract ECP than those with
      positive viral findings (515 vs. 240 ng/g; P = 0.01). The concentration of ECP in
      respiratory secretions decreased significantly after bronchiolitis (P = 0.01)
      provided that no new viral or mycoplasmal infection occurred. NPA ECP values
      decreased in relation to time regardless of whether anti-inflammatory therapy was
      used or not. Children with high concentrations of respiratory tract ECP seemed to
      benefit from anti-inflammatory therapy with nebulized cromolyn sodium or
      budesonide; both drugs significantly decreased the number of subsequent physician
      diagnosed bronchial obstruction (P = 0.0006), and they tended to decrease the
      number of hospital admissions for wheezing (P = 0.08). Our results suggest that
      high concentrations of ECP in respiratory tract secretions in children with
      bronchiolitis reflect the presence of eosinophilic inflammation also seen in
      asthma.

PMID- 9261852
TI  - Effectiveness of home versus hospital care in the routine treatment of cystic
      fibrosis.
AB  - Many cystic fibrosis patients with Pseudomonas lung infections receive
      intravenous (IV) antibiotics and chest physiotherapy (CPT) at home. Previous
      studies have suggested that home care, in the setting of a clinical study, is as
      efficacious as hospital care. This report compares the outcomes of home care with
      minimal supervision to outcomes of hospital care. We compared two groups of
      similar age and severity of lung impairment. Patients met strict definitions for
      home or hospital treatment (27 home care courses/33 hospital care courses). Five
      patients completed six courses of both home care and hospital treatment.
      Treatment in both groups included intravenous antibiotics and CPT. Primary
      outcome measures included changes in pulmonary function between the start of
      treatment and after 2 weeks of therapy, duration of treatment, and intervals
      between antibiotic courses. In hospitalized patients, forced vital capacity (FVC)
      increased by 17.4 +/- 3.1% (mean +/- SEM), and forced expiratory volume in one
      second (FEV1) increased by 23.3 +/- 4.1%, both significant at P < 0.001. The FVC
      and FEV1 of patients treated at home increased by 10.2 +/- 2.0% and 13.7 +/- 2.6%
      respectively, neither of which was a significant improvement. Similar results
      were found in the five patients completing both home and hospital courses. The
      average duration of treatment was twice as long and time between IV antibiotic
      courses only two-thirds as long for those treated at home compared with the
      hospitalized patients. Previous reports have claimed that home care in the
      setting of a prospective study is as efficacious as hospital care. Our experience
      indicates that routine home care with minimal supervision of patients is less
      effective than hospital care. Furthermore, home care as delivered to patients in
      this report increased the overall cost of care by as much as 30% because of
      longer and more frequent courses of antibiotic therapy.

PMID- 9261853
TI  - Lower respiratory illness in infants and young children with cystic fibrosis:
      evaluation of treatment with intravenous hydrocortisone.
AB  - The purpose of our study was to assess the effect on pulmonary function of adding
      intravenous hydrocortisone to the standard treatment of infants with cystic
      fibrosis (CF) hospitalized for lower respiratory illnesses (LRI). Twenty CF
      infants were randomized and received 10 days of hydrocortisone (10 mg/kg/day) or
      placebo in addition to standard treatment with intravenous antibiotics, chest
      physiotherapy, and an aerosolized beta-agonist with cromolyn. Functional residual
      capacity (FRC) and forced expiratory flows (V'mak,FRC) were measured on
      admission, on Day 10 of hospitalization, and as outpatients 1-2 months following
      hospital discharge. Pulmonary function values were adjusted for differences in
      body length and expressed as Z-scores. Upon admission flows were decreased, and
      FRC was increased in both groups; there were no differences between the groups.
      The change in pulmonary function from admission to Day 10 of hospitalization was
      not different for the two groups. From admission to outpatient follow-up after
      hospitalization, there was a significant increase in flows for the steroid group,
      but not for the placebo group. In addition, the direction of change in FRC was
      significantly different for the two groups; the steroid group had a small
      decrease in FRC, while the placebo group had a small increase in FRC. These
      findings suggest that the addition of intravenous hydrocortisone to the standard
      treatment of CF infants hospitalized for a LRI may produce a greater or a more
      sustained improvement in lung function following hospitalization.

PMID- 9261854
TI  - Sensation of smell does not determine nutritional status in patients with cystic
      fibrosis.
AB  - Poor nutritional status in patients with cystic fibrosis (CF) is associated with
      increased mortality. Patients with CF often have a decreased sensation of smell
      secondary to recurrent sinus infections or sinus surgery; in other CF
      populations, a decreased sensation of smell has been associated with poor
      nutritional status. We hypothesized that a decreased sensation of smell would be
      associated with worse nutritional status in patients with CF. We studied 50 (26 F
      and 24 M) of 58 consecutive patients with CF (86%) aged 14-53 years (28 +/- 8;
      mean +/- SD) who attended the University of Washington Medical Center from June
      1994 to March 1995 and who agreed to participate. Demographic information was
      obtained, and nutritional status was assessed by ideal body weight, arm muscle
      area, arm fat area, pancreatic sufficiency, insulin-requiring diabetes, vitamins
      A and E levels, albumin, iron, iron binding capacity, ferritin, cholesterol, and
      zinc levels. Objective sensation of small was examined (Sensonics, Philadelphia,
      PA), a sinus compacted tomogram (CT) was performed, and a questionnaire for prior
      sinus symptoms, sinus surgery, medications, and subjective sensation of smell was
      administered. Twenty-seven of 49 subjects (55%) had an objective decrease in
      sensation of smell, 23/50 (46%) had had prior sinus surgery. 46/50 (92%) were
      pancreatic insufficient, and 8/50 (16%) were insulin-requiring diabetics. Weight
      for height ranged from the 38th to 157th percentile (100 +/- 18; mean +/- SD).
      Arm muscle area ranged from the < 5th to the 75th percentile (25 +/- 23; mean +/-
      SD). Arm fat area ranged from the < 5th to the 95th percentile (45 +/- 39; mean
      +/- SD). Sinus CT scans were abnormal in all patients (100%). Patients with
      anosmia were more likely to have had sinus surgery, but their nutritional status
      was no different from that of patients with a normal sensation of smell. We
      conclude that decreased sensation of smell is common in patients with CF,
      especially those with prior sinus surgery. Subjective sensation of smell and
      sinus CT scans were unreliable indicators of a decreased objective sensation of
      smell. In this pilot study, no association was found between sensation of smell
      and nutritional status.

PMID- 9261855
TI  - Massive hemoptysis as the presenting manifestation in a child with
      histoplasmosis.
AB  - A previously healthy and asymptomatic 7-year-old white boy presented with a
      history of two episodes of hemoptysis productive of bright red blood in the 5
      days preceding admission. After admission he developed massive hemoptysis that,
      on bronchoscopy, was noted to be emanating from the right lower lobe. An
      emergency right lower lobe resection was done. Pathological examination revealed
      hilar adenopathy and peripheral lesions with caseating granulomas containing
      yeast, morphologically consistent with Histoplasma capsulatum.

PMID- 9261856
TI  - Severe necrotizing pneumonitis in a child with Mycoplasma pneumoniae infection.
AB  - Lower respiratory tract illness due to Mycoplasma pneumoniae is typically mild
      and self-limited. There are, however, numerous reports of serious and life
      threatening cases of mycoplasma pneumonia in adults. We present a case involving
      a 4-year-old girl with severe mycoplasma infection and necrotizing pneumonitis
      requiring lobectomy. A detailed pathological report is provided.

PMID- 9261857
TI  - Bi-level positive airway pressure (BiPAP) ventilation in an infant with central
      hypoventilation syndrome.
AB  - A 4-month-old baby girl, after a period of apparent good health, began to have
      aphonia, dyspnea, difficulties with swallowing, cyanosis, apnea, and hypopnea
      during sleep that resulted in admission to an intensive care unit for intubation
      and mechanical ventilation. At the age of 9 months she was admitted to our
      hospital with a possible diagnosis of central hypoventilation syndrome. A
      polysomnographic study showed apnea and hypopnea (apnea + hypopnea index = 47.1),
      hypercapnia (mean end-tidal PCO2 89 +/- 15.0 mmHg), and arterial desaturation
      (mean SaO2 91 +/- 1.7%; lowest SaO2 < 50%; 68% of total sleep time at SaO2 below
      93%); the study also showed an absent ventilatory response to CO2, absent cardiac
      responses to apnea during sleep, and right ventricular hypertrophy. Nocturnal
      nasal bi-level positive airway pressure (BIPAP), applied initially at 6 cmH2O and
      gradually increased to 16 cmH2O, caused the sleep-related abnormal respiratory
      events to disappear. End-tidal PCO2 decreased to 39 mmHg, and SaO2 increased to
      94%. After 6 months of nocturnal BiPAP ventricular right hypertrophy reversed and
      arrested growth and hypotonia normalized. The child has tolerated and has
      remained on BiPAP support up to her current age of 3 years and continues to use
      this form of ventilatory assistance without difficulties.

PMID- 9261858
TI  - Indomethacin depresses prostaglandin F2 alpha-induced contraction in guinea-pig
      uterine artery with both intact and denuded endoth.
AB  - The purpose of this study was to explore whether cyclooxygenase products derived
      from endothelium or vascular muscle participate in the response of guinea-pig
      uterine arterial rings to prostaglandin F2 alpha (PGF2 alpha). Contraction to
      PGF2 alpha (0.1-30 microM) occurred with and without endothelium at similar
      potency and efficacy (pEC50 (-log EC50) values respectively 5.87 +/- 0.06 and
      5.97 +/- 0.07; maximal response respectively 78.1 +/- 1.3% and 76.9 +/- 1.5% of
      contraction induced by 126 mM KCl). Indomethacin (3-30 microM) suppressed the
      maximum response to PGF2 alpha and induced a rightward shift of concentration
      response curves, regardless of the presence of endothelium. pIC50 values for
      indomethacin were 4.67 and 4.74 for vessels with and without endothelium,
      respectively. In contrast, the thromboxane synthesis inhibitor OKY-046 (10 and
      100 microM) did not affect the response to PGF2 alpha. We conclude that the PGF2
      alpha-induced contraction in guinea-pig uterine artery is mediated, at least in
      part, through constrictor non-thromboxane prostanoid(s) of vascular muscle
      origin.

PMID- 9261859
TI  - Microdetermination of the thromboxane B3 gas chromatography-selected-ion
      monitoring using [18O]thromboxane B3 as an internal standard.
AB  - We devised a simple and effective purification for the microdetermination of
      thromboxane B3 (TXB3), a hydrolysis product of TXA3- [18O2]TXB3 was synthesized
      by the repeated base-catalyzed hydrolysis of methyl ester derivatives in
      [18O]water, to obtain an internal standard (IS) for the gas
      chromatography/selected ion monitoring (GC/SIM) of TXB3. The methyl ester (ME)
      methoxime (MO)-dimethylisopropylsilyl (DMIPS) ether derivative was prepared, then
      GC/SIM was carried out by monitoring the ion at m/z 668 for TXB3 and that at m/z
      672 for IS. A good linear response over the range of 10 pg approximately 10 ng
      was demonstrated. We were able to detect the levels of TXB3 in the medium of
      human erythroleukemia (HEL) cell cultured with eicosapentaenoic acid (EPA) or
      docosahexaenoic acid (DHA). This method can be used to determine 3-series
      thromboxane in biological samples.

PMID- 9261860
TI  - Acute effects of thromboxane dual blocker (KDI-792) on different portions of
      lower limb blood flow--a study using Doppler ultrasonography and laser Doppler
      flowmetry in type 2 diabetic patients.
AB  - The acute effects of a newly synthesized thromboxane dual blocker (KDI-792), a
      combined thromboxane synthase inhibitor and receptor antagonist, on lower limb
      circulation were examined using two-dimensional color and pulse Doppler
      ultrasonography and laser Doppler flowmetry. A randomized single-masked, placebo
      controlled trial was performed on 36 type 2 diabetic patients with minimally
      impaired baseline flow. The anatomical cross-sectional area (CSA), maximum flow
      velocity (MFV) and flow volume index (FVI) in the right dorsal pedis artery (DPA)
      and right femoral artery (FA) were determined by Doppler ultrasonography before
      and 45 and 90 minutes after the administration of either 100 or 200 mg of KDI-792
      to the dose groups or placebo to the control group. Periflux blood flow (PBF) in
      the right foot was determined simultaneously by laser Doppler flowmetry. Both CSA
      and MFV in the dose groups were significantly increased in both the FA and DPA.
      FVI was markedly increased from 21.4 +/- 3.7 to 68.3 +/- 26.8 in the DPA (M +/-
      SD, P < 0.01) and from 365.4 +/- 35.3 to 771.7 +/- 75.7 in the FA (P < 0.01) in
      the 200 mg dose group. In the 100 mg dose group, FVI was markedly increased from
      20.0 +/- 8.7 to 68.3 +/- 26.8 (P < 0.01) in the DPA and from 372.5 +/- 130.0 to
      677.5 +/- 187.8 (P < 0.01) in the FA. PBF was also increased in both dose groups
      (from 4.15 +/- 1.4 to 7.0 +/- 4.0 ml/min/100 g tissue in the 200 mg dose group, P
      < 0.01), whereas there were no significant changes in either measurement in the
      control group. There were no significant changes in pulse rate or blood pressure
      after administration in either the dosage group or the placebo group. These and
      previous findings indicate that a single administration of KDI-792 markedly
      increases lower limb blood flow and might have a more potent vasodilating effect
      than that of prostaglandin I2 derivatives.

PMID- 9261861
TI  - Role of prostaglandin E2 on amoebic liver abscess formation in hamsters.
AB  - Entamoeba histolytica can modulate macrophage functions and cytokine production
      by a prostaglandin E2 (PGE2) mechanism. To study the participation of PGE2 on
      amoebic liver abscess formation, we tested the effect of the PG synthesis
      inhibitor indomethacin (INDO) on abscess development in hamsters infected
      intrahepatically with E. histolytica trophozoites. Male infected animals had
      higher levels of plasma PGE2 (5.7 +/- 0.7 pg/ml pre-infection; 26.0 +/- 2.0 pg/ml
      7 days postinfection; p < 0.001). INDO prevented this increase, so that infected
      treated and control non-infected animals had similar levels of plasma PGE2. INDO
      reduced liver and abscess weight by 18% and 30% respectively (p < 0.05).
      Cyclooxygenase (COX) activity determination by thin layer chromatography using (1
      14C) arachidonic acid (AA) showed that liver microsomes from infected animals
      produced more PGE2 than controls. COX activity was considerably inhibited in
      infected INDO-treated animals. Our data suggest that E. histolytica can stimulate
      the hepatic production of PGE2 which contributes to pathogenesis of amoebic
      abscesses through generation and support of the inflammation. The partial effect
      of INDO treatment suggests that additional factors are involved.

PMID- 9261863
TI  - Are there dominant membrane protein families with a given number of helices?

PMID- 9261862
TI  - Rat kidney thromboxane synthase: cDNA cloning and gene expression regulation in
      hydronephrotic kidney.
AB  - We isolated a rat homolog of thromboxane (TX) synthase cDNA (-1.8 kb) from the
      kidney with a fragment of human TX synthase cDNA amplified by polymerase chain
      reaction with placenta cDNA as a template. Northern blot analysis has shown that
      rat TX synthase gene is expressed abundantly in lung, liver, and uterus;
      moderately in kidney. TX synthase mRNA expression was up-regulated in
      hydronephrotic kidney made by ureter ligation. In conclusion, we have revealed
      the structure of rat kidney TX synthase. Up-regulation of renal TX synthase,
      which may cause stimulation of TX synthesis, is possibly implicated in the tissue
      injury in hydronephrotic kidney.

PMID- 9261864
TI  - Dichroic statistical model for prediction and analysis of peptide helicity.
AB  - Traditional statistical models for the prediction of peptide helicity are written
      in terms of the mean fractional helicity of the peptide residues. Far ultraviolet
      circular dichroic measurements of peptide solutions are converted to mean
      fractional helicity by partitioning the observed ellipticity between that of a
      perfect helix and a random coil. This partition does not adequately represent the
      ensemble of peptide molecules present in solution that populate imperfect helical
      conformations of quite variable lengths. A new dichroic statistical model has
      been written in terms of ellipticity rather than fractional helical content that
      recognizes (1) the source of ellipticity, peptide bond adsorption; (2) the
      differential ellipticity of peptide bonds in the terminal and interior helical
      turns; and (3) the contributions of each participant in a conformational ensemble
      to the observed ellipticity. Comparative analyses of host/guest peptides
      indicates that significant differences are obtained between residue w and n
      weights and ellipticity values using the traditional and dichroic statistical
      models.

PMID- 9261865
TI  - Accuracy and precision of NMR relaxation experiments and MD simulations for
      characterizing protein dynamics.
AB  - Model-free parameters obtained from nuclear magnetic resonance (NMR) relaxation
      experiments and molecular dynamics (MD) simulations commonly are used to describe
      the intramolecular dynamical properties of proteins. To assess the relative
      accuracy and precision of experimental and simulated model-free parameters, three
      independent data sets derived from backbone 15N NMR relaxation experiments and
      two independent data sets derived from MD simulations of Escherichia-coli
      ribonuclease HI are compared. The widths of the distributions of the differences
      between the order parameters for pairs of NMR data sets are congruent with the
      uncertainties derived from statistical analyses of individual data sets; thus,
      current protocols for analyzing NMR data encapsulate random uncertainties
      appropriately. Large differences in order parameters for certain residues are
      attributed to systematic differences between samples for intralaboratory
      comparisons and unknown, possibly magnetic field-dependent, experimental effects
      for interlaboratory comparisons. The widths of distributions of the differences
      between the order parameters for two NMR sets are similar to widths of
      distributions for an NMR and an MD set or for two MD sets. The linear
      correlations between the order parameters for an MD set and an NMR set are within
      the range of correlations observed between pairs of NMR sets. These comparisons
      suggest that the NMR and MD generalized order parameters for the backbone amide N
      H bond vectors are of comparable accuracy for residues exhibiting motions on a
      fast time scale (< 100 ps). Large discrepancies between NMR and MD order
      parameters for certain residues are attributed to the occurrence of "rare"
      motional events over the simulation trajectories, the disruption of an element of
      secondary structure in one of the simulations, and lack of consensus among the
      experimental data sets. Consequently, (easily detectable) severe distortions of
      local protein structure and infrequent motional events in MD simulations appear
      to be the most serious artifacts affecting the accuracy and precision,
      respectively, of MD order parameters relative to NMR values. In addition, MD
      order parameters for motions on a fast (< 100 ps) timescale are more precisely
      determined than their NMR counterparts, thereby permitting more detailed dynamic
      characterization of biologically important residues by MD simulation than is
      sometimes possible by experimental methods. Proteins 28:481-493, 1997.

PMID- 9261866
TI  - Extent and nature of contacts between protein molecules in crystal lattices and
      between subunits of protein oligomers.
AB  - A survey was compiled of several characteristics of the intersubunit contacts in
      58 oligomeric proteins, and of the intermolecular contracts in the lattice for
      223 protein crystal structures. The total number of atoms in contact and the
      secondary structure elements involved are similar in the two types of interfaces.
      Crystal contact patches are frequently smaller than patches involved in oligomer
      interfaces. Crystal contacts result from more numerous interactions by polar
      residues, compared with a tendency toward nonpolar amino acids at oligomer
      interfaces. Arginine is the only amino acid prominent in both types of
      interfaces. Potentials of mean force for residue-residue contacts at both crystal
      and oligomer interfaces were derived from comparison of the number of observed
      residue-residue interactions with the number expected by mass action. They show
      that hydrophobic interactions at oligomer interfaces favor aromatic amino acids
      and methionine over aliphatic amino acids; and that crystal contacts form in such
      a way as to avoid inclusion of hydrophobic interactions. They also suggest that
      complex salt bridges with certain amino acid compositions might be important in
      oligomer formation. For a protein that is recalcitrant to crystallization,
      substitution of lysine residues with arginine or glutamine is a recommended
      strategy.

PMID- 9261867
TI  - Simulation of protein crystal nucleation.
AB  - To attempt to understand the physical principles underlying protein
      crystallization, an algorithm is described for simulating the crystal nucleation
      event computationally. The validity of the approach is supported by its ability
      to reproduce closely the wellknown preference of proteins for particular space
      group symmetries. The success of the algorithm supports a recent argument that
      protein crystallization is limited primarily by the entropic effects of geometric
      restrictions imposed during nucleation, rather than particular energetic factors.
      These simulations provide a new tool for attacking the problem of protein
      crystallization by allowing quantitative evaluation of new ideas such as the use
      of racemic protein mixtures.

PMID- 9261868
TI  - Generation of pseudonative protein structures for threading.
AB  - The threading approach to protein structure prediction suffers from the limited
      number of substantially different folds available as templates. A method is
      presented for the generation of artificial protein structures, amenable to
      threading, by modification of native ones. The artificial structures so generated
      are compared to the native ones and it is shown that, within the accuracy of the
      pseudoenergy function or force field used, these two types of structures appear
      equally useful for threading. Since a multitude of pseudonative artificial
      structures can be generated per native structure, the pool of pseudonative
      template structures for threading can be enormously enlarged by the inclusion of
      the pseudonative artificial structures.

PMID- 9261869
TI  - On the reaction mechanism of class Pi glutathione S-transferase.
AB  - Theoretical calculations were performed to examine the ionization of the phenolic
      group of Tyr7 and the thiol group of glutathione in aqueous solution and in the
      protein class-pi glutathione S-transferase (GST-Pi). Three model systems were
      considered for simulations in the protein environments the free enzyme, the
      complex between glutathione and the enzyme, and the complex between 1-chloro-2.4
      dinitrobenzene, glutathione, and the enzyme. The structures derived from
      Molecular Dynamics simulations were compared with the crystallographic data
      available for the complex between the inhibitor S-(p-nitrobenzyl)glutathione and
      GST-Pi, the glutathione-bound form of GST-Pi, and the free enzyme
      carboxymethylated in Cys47. Free-energy perturbation techniques were used to
      determine the thermodynamics quantities for ionization of the phenol and thiol
      groups. The functional implications of Tyr7 in the activation of the glutathione
      thiol group are discussed in the light of present results, which in agreement
      with previous studies suggest that Tyr7 in un-ionized form contributes to the
      catalytic process of glutathione S-transferase, the thiolate anion being
      stabilized by hydrogen bond with Tyr7 and by interactions with hydrating water
      molecules.

PMID- 9261870
TI  - Molecular mechanic study of nerve agent O-ethyl S-[2
      (diisopropylamino)ethyl]methylphosphonothioate (VX) bound to the active site of
      Torpedo californica acetylcholinesterase.
AB  - Herein a molecular mechanic study of the interaction of a lethal chemical warfare
      agent, O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (also called
      VX), with Torpedo californica acetylcholinesterase (TcAChE) is discussed. This
      compound inhibits the enzyme by phosphonylating the active site serine. The
      chirality of the phosphorus atom induces an enantiomeric inhibitory effect
      resulting in an enhanced anticholinesterasic activity of the SP isomer (VXS)
      versus its RP counterpart (VXR). As formation of the enzyme-inhibitor Michaelis
      complex is known to be a crucial step in the inhibitory pathway, this complex was
      addressed by stochastic boundary molecular dynamics and quantum mechanical
      calculations. For this purpose two models of interaction were analyzed: in the
      first, the leaving group of VX was oriented toward the anionic subsite of TcAChE,
      in a similar way as it has been suggested for the natural substrate
      acetylcholine; in the second, it was oriented toward the gorge entrance, placing
      the active site serine in a suitable position for a backside attack on the
      phosphorus atom. This last model was consistent with experimental data related to
      the high inhibitory effect of this compound and the difference in activity
      observed for the two enantiomers.

PMID- 9261871
TI  - ESCHER: a new docking procedure applied to the reconstruction of protein tertiary
      structure.
AB  - Evaluation of Surface Complementarity, Hydrogen bonding, and Electrostatic
      interaction in molecular Recognition (ESCHER) is a new docking procedure
      consisting of three modules that work in series. The first module evaluates the
      geometric complementarity and produces a set of rough solutions for the docking
      problem. The second module identifies molecular collisions within those
      solutions, and the third evaluates their electrostatic complementarity. We
      describe the algorithm and its application to the docking of cocrystallized
      protein domains and unbound components of protein-protein complexes. Furthermore,
      ESCHER has been applied to the reassociation of secondary and supersecondary
      structure elements. The possibility of applying a docking method to the problem
      of protein structure prediction is discussed.

PMID- 9261872
TI  - Flexible glycine rich motif of Escherichia coli deoxyuridine triphosphate
      nucleotidohydrolase is important for functional but not for structural integrity
      of the enzyme.
AB  - Deoxyuridine triphosphate nucleotidohydrolase (dUTPase), a ubiquitous enzyme of
      DNA metabolism, has been implicated as a novel target of anticancer and antiviral
      drug design. This task is most efficiently accomplished by X-ray crystallography
      of the relevant protein-inhibitor complexes. However, the topic of the present
      investigation, a glycine-rich strictly conserved structural motif of dUTPases,
      could not be located in the crystal structure of the Escherichia coli enzyme,
      probably due to its increased flexibility. The present work shows that removal of
      a C-terminal 11-residue fragment, including this motif, by limited trypsinolysis
      strongly impairs catalytic activity. Kinetic analysis of the intact and digested
      variants showed that kcat decreases 40-fold, while KM increases less than twofold
      upon digestion. The tryptic site was identified by mass spectrometry, amino acid
      analysis and N-terminal sequencing. The shortened enzyme variant retains the
      secondary, tertiary, and quaternary (trimeric) structure of the intact species as
      suggested by UV absorption, fluorescence and circular dichroism spectroscopy, and
      analytical gel filtration. Moreover, binding affinity of the shortened variant
      toward the substrate analogue MgdUDP is identical to the one displayed by the
      intact enzyme. I conclude that the glycine-rich motif is functionally relevant
      for E. coli dUTPase. It may play a role in enzymatic catalysis by contributing to
      the formation of the catalytically potent enzyme-substrate complex.

PMID- 9261873
TI  - Crystals of cytochrome c-553 from Bacillus pasteurii show diffraction to 0.97 A
      resolution.
AB  - We report here the purification and characterization of a c-type cytochrome
      present in the soluble fraction of the gram-positive, alkaliphilic, and highly
      ureolytic soil bacterium Bacillus pasteurii. The cytochrome is acidic (pI = 3.3),
      has a molecular mass of 9.5 kDa, and appears to dimerize in 150 mM ionic strength
      solution. The electronic spectrum is typical of a low-spin hexa-coordinated heme
      iron. Crystals of the protein in the oxidized state were grown by vapor diffusion
      at pH 5, by using 3.2 M ammonium sulfate as precipitant. Diffraction data at
      ultrahigh resolution (0.97 A) and completeness (99.9%) have been collected under
      cryogenic conditions, by using synchrotron radiation. The crystals belong to the
      orthorhombic space group P2(1)2(1)2(1), with cell constants a = 37.14, b = 39.42,
      c = 44.02 A, and one protein monomer per asymmetric unit. Attempts to solve the
      crystal structure by ab initio methods are in progress.

PMID- 9261874
TI  - Preliminary crystallographic characterization of ricin agglutinin.
AB  - The quaternary structure of ricin agglutinin (RCA) has been determined by x-ray
      crystallography. The refined structure of ricin proved to be a successful search
      model using the molecular replacement method of phase determination. RCA forms an
      elongated molecule of dimensions 120 A x 60 A x 40 A with two A chains at the
      center and a B chain at each end. The A chains are covalently associated via a
      disulfide bridge between Cys 156 of both chains. Additional contacts at residues
      114-5 stabilize the dimer interface. The covalent association of RCAA chains was
      confirmed by gel filtration under reducing and nonreducing conditions.

PMID- 9261875
TI  - Crystallization of the RNA-binding domain of the transcriptional antiterminator
      protein SacY from Bacillus subtilis.
AB  - SacY is the antiterminator protein involved in the induction by sucrose of the
      expression of the levansucrase gene (sacB) of Bacillus subtilis. In the presence
      of sucrose, SacY is activated and prevents premature termination of transcription
      by binding to a RNA-antiterminator (RAT) sequence partially overlapping with the
      terminator sequence. SacY consists of a RNA-binding N-terminal domain, SacY(1
      55), and a regulatory domain, SacY(56-280), sensitive to the sucrose
      concentration. SacY(1-55) is in itself capable of binding to the RAT sequence and
      preventing termination independently of the sucrose concentration. In this paper
      we describe the overexpression, the purification, and the crystallization of
      SacY(1-55). We obtained six different crystal forms, some of them diffracting to
      high resolution (> 1.5 A). Self rotation function calculations indicated the
      presence of a dimer in the asymmetric unit, which is in agreement with a proposed
      oligomeric state in solution as observed by high-resolution NMR measurements. The
      crystallization of some site-directed cysteine mutants opens the way of solving
      the structure by multiple isomorphous replacement.

PMID- 9261876
TI  - Mitochondrial function and ram sperm fertility.
AB  - These experiments investigated the effect of freezing on mitochondrial function
      in ram sperm, the effectiveness of current freezing procedures in protecting
      mitochondria, and the role of mitochondrial respiration in cervical penetration
      and transit by ram sperm. Only sperm with functioning mitochondria (assessed by
      rhodamine 123 staining) after freezing and thawing were motile in a viscous
      medium (P < 0.05). A simplified rhodamine 123 uptake assay was developed to
      monitor sperm mitochondrial function. The results of this procedure were highly
      correlated (r2 = 0.98) with the proportion of damaged sperm in the semen sample.
      A semen freezing procedure commonly used by industry was compared with newer
      methods, and with freezing without cryoprotectants. None of the freezing
      protocols produced sperm with higher post-thaw levels of mitochondrial integrity
      than unprotected sperm. Merino ewes were inseminated with semen treated with
      metabolic inhibitors. Glycolytic inhibition did not affect fertility.
      Mitochondrial inhibition reduced fertility in cervically (P < 0.05), but not
      laparoscopically inseminated ewes. It is concluded that mitochondrial respiration
      plays an important part in penetration of the cervix by ram sperm. Mitochondrial
      injury during freezing is likely to be implicated in the poor fertility of frozen
      ram semen used for cervical insemination.

PMID- 9261878
TI  - Evaluation of sperm damage and techniques for sperm clean-up.
AB  - The cryopreservation of bull semen adversely affects the metabolism, motility and
      membrane integrity of the spermatozoa, thereby decreasing the fertilizing ability
      of the processed sample. The present review covers methods available for
      examining the functionality of bull spermatozoa after thawing, including the use
      of fluorophores in combination with morphological examination. Procedures for
      clean-up, separation and selection of morphologically-normal, viable spermatozoa
      in vitro are also reviewed. Among the reviewed procedures are methods for
      dilution and washing and the selective fractionation of sperm subpopulations
      (especially density-gradient centrifugation in silica-bead suspensions), as well
      as methods based on adherence to glass (differential filtration) and sperm self
      migration (particularly swim-up through hyaluronic acid). Emphasis is placed on
      assessing the value of these techniques for diagnostic purposes and for
      optimizing the methodology of in vitro fertilization.

PMID- 9261877
TI  - Seasonal effects on ovarian responsiveness to exogenous gonadotrophins and
      successful artificial insemination in the snow leopard (Uncia uncia).
AB  - Ovaries of the seasonally-breeding snow leopard (Uncia uncia) were examined to
      determine whether they were responsive to exogenous gonadotrophins throughout the
      year. The potential of laparoscopic artificial insemination (AI) also was
      assessed for producing offspring. During the non-breeding, pre-breeding, breeding
      and post-breeding seasons, females (n = 20) were treated with a standardized,
      dual-hormone regimen given intramuscularly (600 I.U. of equine chorionic
      gonadotrophin followed 80-84 h later with 300 I.U. of human chorionic
      gonadotrophin (hCG)). Laparoscopy was performed 45-50 h after administration of
      hCG, and all ovarian structures were described. Females with fresh corpora lutea
      (CL) were inseminated, and anovulatory females were subjected to follicular
      aspiration to examine oocyte quality. Snow leopards responded to exogenous
      gonadotrophins throughout the year. Mean number of total ovarian structures
      (distinct follicles mature in appearance plus CL) did not differ (P > or = 0.05)
      with season, but the proportion of CL: total ovarian structures was greater (P <
      0.01) for the breeding season compared with all other seasons. The proportion of
      females ovulating was greater (P < 0.05) during the breeding and post-breeding
      seasons than during the pre-breeding and non-breeding seasons respectively. No
      Grade-1 quality oocytes were recovered from follicles of anovulatory females.
      Serum concentrations of oestradiol-17 beta appeared elevated in all females, and
      neither oestradiol-17 beta concentrations nor progesterone concentrations
      differed (P > or = 0.05) among seasons. Of 15 females artificially inseminated,
      the only one that was inseminated in the non-breeding season became pregnant and
      delivered a single cub. This is the first successful pregnancy resulting from AI
      in this endangered species.

PMID- 9261879
TI  - Alternative strategies for the long-term preservation of spermatozoa.
AB  - A number of perceived future requirements for stored germplasm in agriculture,
      aquaculture, biotechnology and conservation are discussed in the present review.
      In the light of these broad demands, it is apparent that current approaches to
      gamete and embryo storage need considerable improvement, and that novel
      approaches to the technologies of germplasm preservation should be pursued if
      possible. The present article is presented in response to a request for novel
      future research ideas in this area. Early literature on desiccation, and later
      research into natural mechanisms of survival during desiccation, is considered in
      relation to the development of freeze-drying and vitrification methods.
      Developments in reproductive technologies themselves may mean that freeze-dried
      spermatozoa could realistically be used for direct intracytoplasmic
      microinjection of oocytes. Other radical methods that may achieve germplasm
      preservation are harvesting testicular cells in culture, cryopreserving immature
      or seasonally regressed testicular material, or a combination of both. Evidence
      from non-mammalian testicular culture systems, and recent success with the
      transmeiotic development of mouse spermatids in vitro, suggest that these
      approaches may eventually become feasible.

PMID- 9261880
TI  - Do sperm cells age? A review of the physiological changes in sperm during storage
      at ambient temperature.
AB  - In a liquid environment, at high dilutions, fertility of bull sperm is maintained
      for 3-5 days when stored at ambient temperatures (10-21 degrees C), after which
      time it steadily declines at a rate of 3-6% per day. This decline in fertility
      occurs irrespective of whether the sperm are stored at 5 degrees C or at 15
      degrees C, but the rate is greater once storage temperatures exceed 25 degrees C.
      Sperm motility can be maintained for extended periods in an environment where the
      extracellular oxidative stress is minimized by reducing the oxygen tension, by
      addition of antioxidants and chelating agents; however, this will not prevent a
      significant drop in fertility after five days of storage at ambient temperature.
      The requirement of energy by the sperm-motility apparatus demands a high level of
      respiratory activity. This system is very active and the free radicals produced
      in vivo during this process could lead to chromatin damage. As no internal repair
      mechanism exists in sperm, an extraneous supply of protectants, or an environment
      where damage is minimized, is essential to maintain its fertilizing potential.
      The lack of extended storage potential of sperm, even in the presence of
      antioxidants, seems to suggest that although oocyte-penetrating ability of the
      sperm could still be intact, the high rate of intracellular metabolic activity
      could lead to mitochondrial DNA damage and chromosomal abnormalities that would
      compromise the viability of the resulting conceptus.

PMID- 9261881
TI  - Advances in production of embryos in vitro from juvenile and prepubertal oocytes
      from the calf and lamb.
AB  - The use of juvenile donors in embryo-transfer (ET) programmes offers considerable
      potential for accelerated genetic gain in domestic livestock through reduced
      generation interval. The present paper reviews recent research aimed at
      optimizing embryo production from oocytes collected from young calves and lambs
      using in vitro methods of embryo production. Emphasis is placed on criteria for
      donor selection, oocyte-collection methods, and hormone-stimulation methods
      designed to produce maximum yields of viable oocytes. In vitro fertilization
      (IVF) rates of calf and lamb oocytes did not differ significantly whether matured
      in vivo or in vitro, and rates of development of blastocyst stages in culture
      were similar to those observed for embryos derived from adult donors. Blastocysts
      produced by IVF of lamb and calf oocytes established ET pregnancies at rates of
      30-45%. Pregnant recipients have reached full term and delivered normal offspring
      at rates similar to those expected following ET of embryos produced in vivo from
      superovulated donors. On the basis of current follicle-stimulation protocols, on
      rates of blastocyst production in vitro under optimal conditions, and on observed
      pregnancy rates from fresh transfer of IVF embryos, 8-10 pregnancies may be
      expected per oocyte collection from 10-12-week-old calves and from 6-8-week-old
      lambs.

PMID- 9261882
TI  - Comparison between in vivo-derived and in vitro-produced pre-elongation embryos
      from domestic ruminants.
AB  - In vitro production of ruminant embryos has become routine and is increasingly
      available as a commercial service to dairy, meat and wool producers. However, the
      efficiency of producing viable embryos and the development of such embryos after
      transfer to recipients are perceived to be inferior to that which occurs in vivo.
      The present review outlines the biochemical and morphological similarities and
      differences between embryos produced in vitro and those produced in vivo. Some
      measures of metabolism are not markedly different between in vitro- and in vivo
      derived blastocysts. However, at a cellular and subcellular level, differences in
      metabolism, morphology and ultrastructure have been described, as has
      susceptibility to manipulation and cryopreservation. Most importantly are the
      differences in lambing and calving rates and the reports of abnormal fetal
      development from embryos produced in vitro. These latter observations are of
      major concern, as they suggest that the in vitro environment may affect
      subsequent developmental physiology. At the extreme, these effects may not be
      expressed until adult life. Further efforts to improve the efficiency of in vitro
      embryo production must be accompanied by a commitment to assess the long-term
      consequences of these procedures.

PMID- 9261884
TI  - The alteration of cytokeratin 18 molecule and its mRNA expression during tumor
      transformation in hepatoma.
AB  - The cytokeratin 18 related molecules of human hepatocellular carcinoma have been
      previously recognized through a series of biochemical and immunological
      approaches. It is suggested that these molecules undergo modulation from human
      hepatocyte cytokeratin 18. To prove whether these molecules are produced by
      modulation or protein degradation, we checked the cytokeratin profile of human
      hepatoma cell line PLC/PRF/5 with the methods used before. These results revealed
      that the PLC cells have the same cytokeratin 18 related molecules as human
      hepatocellular carcinoma tissue. The gene expression of the cytokeratin 18 in non
      tumor liver tissues, hepatocellular carcinoma and PLC/PRF/5 cells were
      investigated. First, the mRNAs of non-tumor liver tissues, hepatocellular
      carcinoma tissues and PLC/PRF/5 cells were collected by the acid guanidinium
      thiocyanate phenol chloroform method. After transcription into cDNA by reverse
      transcriptase polymerase chain reaction, the cDNAs of each specimen were
      amplified by PCR and then digested by SmaI and BamHI restriction enzymes. The
      digested cDNA fragments were electrophoresed in agarose gel and the base pairs
      were found to be the same in length between neoplastic and non-neoplastic
      hepatocytes.

PMID- 9261883
TI  - Recent developments and potentialities for reducing embryo mortality in
      ruminants: the role of IFN-tau and other cytokines in early pregnancy.
AB  - This review considers the potential reduction of embryo mortality in vitro and in
      vivo in ruminants. Data on cytokines provided by different fields of reproductive
      immunology and biology were collated. Because of the crucial importance of the
      local interactions between the embryo and its dam, the expression of growth
      factor and cytokine genes was analysed in the embryo proper, trophoblast, oviduct
      and endometrium by reverse transcriptase polymerase chain reaction in sheep and
      in cattle during the pre- and periimplantation periods. Many deleterious
      cytokines, such as tumour necrosis factor-alpha, interferon-gamma (IFN-gamma),
      interleukin-2 (IL-2), and beneficial cytokines, such as transforming growth
      factor-beta, leukaemia inhibiting factor, colony-stimulating factor-1 (CSF-1),
      granulocyte-macrophage CSF, IL-1, IL-3, IL-4, IL-6, IL-10 and IFN-tau appeared to
      be involved in embryo survival in ruminants and other species. Their
      administration is efficient in a murine experimental model (CBA/J x DBA/2) of
      embryonic and fetal mortality. For instance, recombinant ovine IFN-tau (roIFN
      tau) injected at the moment of implantation drastically reduces embryonic
      mortality in this model. In ruminants, roIFN-tau and recombinant bovine IFN-tau
      are very efficient in maintaining progesterone luteal secretion in cyclic
      animals. The involvement of IFN-tau in the mechanisms of maternal pregnancy
      recognition are particularly detailed in relation to inhibition of 13,14 dihydro
      15-keto-prostaglandin F2 alpha (PGFM) pulses and oxytocin uterine receptivity. A
      synthetic model of the anti-luteolytic effects of IFN-tau on the endometrial cell
      is proposed. Finally, the particular potential of serum pregnancy-specific
      proteins (PSPs: PSPB, PSP60, pregnancy-associated glycoprotein) for monitoring
      embryo survival, with examples given for cattle and sheep is underlined.

PMID- 9261886
TI  - Kidney as an important metabolic organ for recombinant human insulin-like growth
      factor-I.
AB  - To investigate the kidney as a metabolic organ of recombinant human insulin-like
      growth factor-I (rhIGF-I), a single chain polypeptide consisting of 70 amino
      acids, the renal extraction and urinary excretion of rhIGF-I were examined in
      rats. The distribution of rhIGF-I after subcutaneous administration and the
      degradation in various tissue homogenates were also studied to evaluate the
      contributions of the other tissues to its metabolism. Although potent enzymes
      capable of degrading rhIGF-I exist in other tissues, no other organ except the
      kidney seemed to play a specific role in clearing rhIGF-I from the systemic
      circulation.

PMID- 9261885
TI  - Mechanism(S) of interferon inhibitory activity in blood from patients with AIDS
      and patients with lupus erythematosus with vasculitis.
AB  - We have earlier reported that patients suffering from acquired immuno-deficiency
      syndrome (AIDS), systemic lupus erythematosus (SLE) with vasculitis, Wegner
      granulomatosis and certain types of late stage cancer have interferon inhibitory
      activity in their serum. The purpose of this study was to identify the factor(s)
      involved in this interferon inhibitory activity. Twenty patients with advanced
      AIDS, twenty patients with SLE and vasculitis and twenty normal healthy controls
      between ages 25-40 years were studied. In contrast to normal, healthy controls,
      significant interferon inhibitory activity was found in AIDS and SLE patients.
      This appears to be largely due to: (a) increased soluble circulating interferon
      alpha/beta receptors, (b) increased prostaglandin E2 levels which inhibits
      interferon and (c) a interferon inhibitory protein. Further understaging of the
      nature of interferon inhibitory activity in the patient's sera and development of
      anti-interferon inhibitory agents would greatly enhance interferons potential as
      a treatment modality.

PMID- 9261887
TI  - Phospholipase A2 is activated in the kidney, but not in the liver during ischemia
      reperfusion.
AB  - Phospholipase A2 (PLA2) has been demonstrated to play an important role in the
      reperfusion injury of the kidney, gut, brain, heart and pancreas. This study was
      carried out to clarify whether PLA2 was involved in the ischemia-reperfusion
      injury of the liver. Rats were anesthetized and underwent laparotomy. They were
      allocated into one of 4 groups, i.e., the groups of renal ischemia (group RI),
      renal control (group RC), hepatic ischemia (group HI), and hepatic control (group
      HC). In group RI, the left renal pedicle was occluded for 1 hr, and the left
      kidney was removed after 1-hr reperfusion. In group HI, the portal and the
      hepatic artery supplying the left and middle lobes were clamped for 1 hr,
      followed by reperfusion. After predetermined periods of reperfusion up to 24 hr,
      the ischemic lobes were removed, homogenized and centrifuged. PLA2 activities in
      the mitochondrial fraction and the cytosolic fraction were measured with 14C
      phosphatidylcholine (PC) and 14C-phosphatidylethanolamine (PE) as exogenous
      substrates. PLA2 activities of the both fractions in the kidney were
      significantly enhanced after 1-hr ischemia followed by 1-hr reperfusion. However,
      there was no enhancement of PLA2 activity of the either fraction in the group HI
      compared with the group HC. The results indicate that PLA2 is activated in the
      kidney but not in the liver during ischemia-reperfusion.

PMID- 9261888
TI  - Inhibition of microsomal glucose-6-phosphatase induced by ferrylmyoglobin.
AB  - Ferrylmyoglobin (ferrylMb) caused inhibition of microsomal glucose-6-phosphatase
      (G6Pase) during membrane lipid peroxidation. Butylated hydroxytoluene prevented
      both the inactivation of G6Pase and the lipid peroxidation. Furthermore, ferrylMb
      was adsorbed on to the membranes and the membrane proteins polymerized during the
      lipid peroxidation, suggesting that the inactivation of microsomal G6Pase was due
      to the disturbance of the membrane structure induced by ferrylMb.

PMID- 9261889
TI  - Pharmacokinetics of adriamycin and adriamycinol after intravenous administration
      of adriamycin to rats with water-deprivation for 48 hours.
AB  - Because hormonal, physiological, and biochemical changes occurring in dehydrated
      patients could alter the pharmacokinetics of the drugs used to treat the
      patients, the pharmacokinetics and tissue distribution of adriamycin (ADM) and
      adriamycinol were investigated after 1-min intravenous administration of ADM (16
      mg kg-1) to control and 48-h water-deprived rats. After intravenous
      administration of ADM, the plasma levels of ADM were considerably higher from 3 h
      in water-deprived rats (n = 10) than those in control rats (n = 11). The total
      body clearance was significantly slower (80.3 compared with 110 mL min-1 kg-1) in
      water deprived rats than that in control rats. Adriamycinol was detected in
      plasma up to 30 min for water-deprived rats, but it was detected only up to 5 min
      for control rats with considerably higher levels in water-deprived rats. The
      amount of ADM obtained from kidney, liver, spleen, and small intestine was
      significantly higher in water-deprived rats (n = 6) than those in control rats (n
      = 5). The amount of adriamycinol obtained from liver was significantly higher in
      water-deprived rats. All 11 control rats survived over 48 h whereas 5 water
      deprived rats died within 8 h after intravenous administration of ADM, suggesting
      that the intravenous dose of ADM in water-deprived patients may need modification
      if the present rat data could be extrapolated to humans.

PMID- 9261890
TI  - Effect of 2,4-disubstituted thiazol-5yl-aminoketones on inflammation. In vitro
      and in vivo biological studies: a structure-activity approach.
AB  - Some modified novel thiazol-5yl-aminoketones were evaluated for their anti
      inflammatory, analgesic and antiproteolytic activities. Their inhibitory activity
      on 12-lipoxygenase (12-LO) and beta-glucuronidase in vitro was estimated. Their
      interaction with the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) and
      their RM values were also determined. For two of them, the effect on zoxazolamine
      induced paralysis after a prolonged treatment was determined. The duration of
      paralysis for the same compounds, (only one administration, one before
      zoxazolamine injection) was recorded too. The 2-amino substituted derivatives
      seem to be more potent in comparison with the 2-phenyl. The tested compounds were
      found to influence proteolysis but not the activities at beta-glucuronidase and
      12-LO. Their interaction with DPPH was mild. Compound 2 seems to modify the
      activity of the hepatic drug metabolizing enzymes. In conclusion, their activity
      is related to certain structural characteristics.

PMID- 9261891
TI  - Characteristics of contractile responses of aorta to norepinephrine in db/db
      mice.
AB  - In the isolated mouse aorta with endothelium, although norepinephrine (NE) showed
      only a slight increase in tension in control mice, the NE-induced dose-dependent
      contraction was markedly increased in spontaneously diabetic mice. NE-induced
      contractile responses were significantly enhanced by pretreatment with 10(-4) NG
      monomethyl-L-arginine (L-NMMA), 5 micrograms/ml lysophosphatidylcholine (LPC),
      and the combined treatment with L-NMMA and LPC. When the aortic ring was
      precontracted with 3 x 10(-6) M PGF2 alpha, NE (10(-8) to 3 x 10(-5) M) caused
      dose-dependent relaxation. The NE-induced relaxation was significantly inhibited
      by 10(-4) L-NMMA or 5 micrograms/ml LPC in the normal mice. These results suggest
      that insensitivity of the mouse aorta to NE is due to the release of nitric oxide
      from the endothelium, and that an increased contraction induced by NE in
      spontaneously diabetic mice is due to an impairment of the endothelium.

PMID- 9261892
TI  - Alpha 1-adrenoceptor mediated activation of Na/K/2Cl cotransport and K+ channels
      in the rat heart involves different receptor subtypes.
AB  - Involvement of receptor subtypes in the alpha 1-adrenoceptor mediated activation
      of Na/K/2Cl-cotransport and K+ channels was studied in isolated perfused
      spontaneously beating rat hearts stimulated by phenylephrine (30 mumol/l) in the
      presence of a beta-adrenoceptor antagonist (1 mumol/l timolol). The effects of
      alpha 1-adrenoceptor stimulation on K+ translocation mechanisms were studied by
      measuring the efflux of 86Rb+ (a potassium analogue). The effects of 50 mumol/l
      bumetanide (Na/K/2Cl-cotransport inhibitor) and 0.1-0.3 mmol/l 4-aminopyridine
      (inhibitor of K+ channels) were studied in the presence of alpha 1-adrenoceptor
      subtype selective antagonists. Bumetanide reduced the alpha 1-adrenoceptor
      mediated increase in 86Rb+ efflux by 53 +/- 16.4% (n = 14, P < 0.001) in hearts
      pretreated with the preferentially alpha 1B-adrenoceptor antagonist
      chloroethylclonidine (CEC, 10 mumol/l), and by 35 +/- 7.3% (n = 15, P < 0.001) in
      the presence of the preferentially alpha 1D-adrenoceptor antagonist BMY 7378 (1
      mumol/l). In the presence of the preferentially alpha 1A-adrenoceptor antagonist
      5-methylurapidil (10 mumol/l), however, bumetanide had no effect on the response
      to phenylephrine. 4-Aminopyridine reduced the phenylephrine stimulated 86Rb+
      efflux in the presence of 5-methylurapidil, but the effect of the K(+)-channel
      blocker was eliminated in CEC treated hearts. Thus the effects of the two
      translocation inhibitors were influenced differently by the two subtype selective
      antagonists, showing that alpha 1-adrenoceptor stimulation activates a bumetanide
      sensitive Na/K/2Cl-cotransport mechanism in the rat heart mainly through the
      alpha 1A-receptor subtype while the 4-aminopyridine sensitive K+ channels, are
      mainly activated by the alpha 1B-adrenoceptor subtype.

PMID- 9261893
TI  - Characterization of plasmin-induced platelet aggregation.
AB  - This study was undertaken to determine if reocclusion after treatment of
      myocardial infarction with a tissue-plasminogen activator (t-PA) may be due to
      plasmin-induced platelet aggregation. t-PA caused platelet aggregation by
      conversion of plasminogen to plasmin under certain conditions. Plasmin-induced
      platelet aggregation was inhibited by serine protease inhibitors, aprotinin and
      bdellin, and a lysine binding site inhibitor, epsilon-aminocaproic acid (EACA).
      Extracellular [Ca2+], and RGDS sequence-dependent steps were involved in the
      aggregation process. The action of plasmin was inhibited by large thrombin
      antagonistic molecules such as argatroban-inactivated thrombin or anti-thrombin
      receptor peptide antibodies but not by small molecules like thrombin receptor
      antagonist peptides. This suggests that target molecules of plasmin on the
      surface of platelets may not be thrombin receptors but may exist very close to
      thrombin receptors. Binding experiments using FITC-labeled plasmin showed that
      plasmin has its binding sites on platelets. Flow cytometric analyses with four
      types of anti-plasmin(ogen) monoclonal antibodies suggested that plasmin might
      bind to platelets through the N-terminal region. The binding of plasmin to
      platelets was suppressed by aprotinin and EACA, furthermore indicating that
      protease catalytic sites and lysine binding regions are involved in interaction
      of plasmin to platelet.

PMID- 9261894
TI  - Mitochondrial lipid peroxides and antioxidant enzymes in the liver following
      phorone-induced glutathione depletion.
AB  - The levels of lipid peroxidation product (malondialdehyde = MDA) and vitamin C
      and the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase
      (SOD) were determined in the liver and its mitochondrial fraction, in the rats 2
      and 18 hr after the injection of phorone, a glutathione (GSH) depleting agent.
      GSH levels decreased in liver homogenate and its mitochondrial fraction after 2
      hr of phorone treatment, but these values returned to normal levels at 18 hr. In
      GSH depleted conditions, hepatic vitamin C levels increased, GSH-Px and SOD
      activities remained unchanged in mitochondrial and post-mitochondrial fractions.
      These results indicate that GSH depletion per se does not influence lipid
      peroxidation and GSH-Px and SOD activities in the liver and the mitochondrial
      fraction.

PMID- 9261896
TI  - Remodeling of hepatic microvascular responsiveness after ischemia/reperfusion.
AB  - Although there is substantial evidence suggesting that the integrity of the
      microcirculation is an important determinant of tissue viability during
      reperfusion after ischemia in the liver, as well as other tissues, the mechanisms
      responsible for microvascular failure are not fully understood. It is now
      recognized that the microvascular response to reperfusion, similar to the whole
      organism response to shock, can consist of either a rapid exacerbation of injury
      after a severe ischemic episode or, alternatively, a more slowly developing
      alteration in responsiveness that occurs after a less severe insult. In the more
      slowly developing response, the alterations in vascular status are the result of
      up-regulation of stress-induced vascular mediators such as endothelin, nitric
      oxide synthase (NOS), and heme oxygenase, as well as changes in the reactivity of
      the effector cells to the mediators. The mechanisms for change in reactivity of
      vascular cells range from changes in receptor expression to overt phenotypic
      transformation, as can occur in the hepatic stellate cells in response to
      repeated injury. When maintained in balance, these counteracting constrictor and
      dilator influences can be protective; however, local imbalance can result in
      focal ischemia, thus propagating the injury. Thus, the remodeling of the hepatic
      microvascular responsiveness during reperfusion after ischemia may serve as a
      useful paradigm for consideration of the overall response of the organism to
      shock.

PMID- 9261895
TI  - The effects of interferon-alpha on serum lipid peroxidation and total thiol
      content in patients with chronic active hepatitis-C.
AB  - Chronic hepatitis develops in at least half of the patients with acute hepatitis
      C. Although there is currently no effective therapy for chronic hepatitis C
      (CHC), it is reported that Interferon-alpha (IFN alpha) has some beneficial
      effects. It has been suggested that changes in the oxidant-antioxidant balance
      may take decisive role in the progression of liver damage in viral hepatitis and
      IFN alpha might be effective in the treatment of liver damage by improving the
      antioxidant system. In the present study, when the patients with chronic active
      hepatitis-C (CAH-C) were compared to controls, serum thiobarbituric acid reactive
      substance (TBARS) levels and glutathione peroxidase (GPx) activity as well as
      transaminase activities were increased, but total sulfhydryl (t-SH) contents were
      decreased Following IFN alpha treatment three times a week for a period of 6
      months, it has been observed that elevated TBARS levels and GPx activity were
      decreased and reduced t-SH contents were increased significantly in patients with
      chronic active hepatitis-C (CAH-C). According to our results, these findings
      suggests that oxidative stress may play an important role in HCV induced liver
      injury and IFN alpha may be useful in treatment by reducing the oxidative stress.

PMID- 9261897
TI  - Mechanisms of ischemic preconditioning.
AB  - Ischemic preconditioning (IPC) refers to a phenomenon in which a tissue is
      rendered resistant to the deleterious effects of prolonged ischemia by previous
      exposure to brief periods of vascular occlusion. While the beneficial effects of
      IPC were first demonstrated in the myocardium, it is now clear that
      preconditioning protects postischemic skeletal muscle, brain, and small intestine
      and may also occur in humans. Although first described over a decade ago, the
      mechanisms underlying the powerful protective effects of IPC remain uncertain.
      However, a growing body of evidence indicates that the beneficial actions of IPC
      involve the activation of adenosine A1 receptors during the period of
      preconditioning ischemia in most organs and species. Adenosine A1 receptor
      stimulation is thought to promote the translocation and activation of specific
      isoforms of protein kinase C1 which in turn phosphorylate as yet unidentified
      cellular effector molecules. In the heart, it has been suggested that ATP
      sensitive potassium channels may represent important effectors of the
      preconditioning phenomenon. In contrast, ATP-sensitive potassium channel
      activation does not seem to contribute to the beneficial effects of IPC in the
      small bowel and seems to play only a limited role in skeletal muscle. In these
      peripheral tissues, the beneficial effects of IPC are related to inhibition of
      leukocyte adhesion and emigration. In the small intestine, IPC seems to prevent
      postischemic leukocyte adhesion by maintaining the bioavailability of nitric
      oxide (a potent endogenous anti-adhesive agent) and preventing, the expression of
      P-selectin (an adhesive molecule expressed by endothelial cells that is thought
      to modulate leukocyte rolling). In skeletal muscle, these actions are mediated by
      an effect of IPC to augment the production of adenosine (another potent
      endogenous anti-adhesive agent) during reperfusion. Thus, although adenosine
      induced protein kinase C activation seems to play an important role in initiating
      the beneficial actions of IPC in most tissues, the effector of the
      preconditioning phenomenon seems to differ among tissues. Understanding the
      mechanisms of IPC has led to the recognition that tissues may also be
      preconditioned by administration of agents that act via the same signaling
      cascade (e.g., adenosine, bradykinin, alpha 1-adrenergic agonists). The purpose
      of this review is to summarize the evidence regarding the mechanisms of IPC in
      different organs.

PMID- 9261898
TI  - Reperfusion of the brain after global ischemia: hemodynamic disturbances.
AB  - Recovery of the brain after a period of cerebral ischemia depends greatly on the
      restoration of nutritive blood flow, which, however, may be severely disturbed.
      Early post-ischemic deficits (no-reflow) multiply with increasing duration of
      ischemia. The pathophysiology is multifactorial and includes vascular factors
      (endothelial blebs, compression by swollen glial cells), blood factors (viscosity
      changes due to erythrocyte sludging, platelet aggregation, blood dehydration),
      and general cardiovascular factors (post-ischemic hypotension, venous
      congestion). Treatment of no-reflow requires a combination therapy (e.g.,
      hypertensive flush, small volume hypertonic solutions, fibrinolysis) for
      interfering with as many of these factors as possible. Delayed post-ischemic
      hypoperfusion develops after a preceding phase of post-ischemic hyperemia and is
      characterized by increased vasotonus. Hypoperfusion is associated with a
      disturbed coupling between brain function, metabolism, and blood flow, and may
      lead to secondary stimulation of anaerobic metabolism. Causal factors include
      disturbed blood/vessel wall interactions (expression of adhesion molecules,
      generation of free radicals) and possibly down-regulation of endothelial nitric
      oxide synthase. Treatment of post-ischemic hypoperfusion includes neutrophil
      elimination and free radical scavengers but is still unsatisfactory. Improvement
      of reperfusion deficits is a challenging task that must be solved before
      proceeding to specific molecular interventions for the treatment of ischemic cell
      injury.

PMID- 9261899
TI  - Effect of crystalloid and colloid solutions on blood rheology in sepsis.
AB  - Sepsis is associated with altered blood rheology. Fluid infusion is an essential
      component of therapy for septic shock. The purpose of this study was to compare
      the rheologic changes associated with saline, albumin, and hydroxyethyl starch in
      sepsis. Whole blood was obtained from five normal controls and five patients with
      severe sepsis. The samples were centrifuged, and the erythrocytes were
      resuspended in autologous plasma or autologous plasma plus the buffy coat at an
      hematocrit (Hct) of 40%. The sample was diluted to an Hct of 30%, 20%, and 10%
      with saline, albumin, or hydroxyethyl starch. Viscosity was measured at low and
      high shear rates and erythrocyte aggregation was measured by the ratio of
      viscosity at low to high shear rates. Erythrocyte deformability was assessed by
      filtration. The viscosity of hydroxyethyl starch was greater than saline,
      albumin, or autologous plasma (p < .01). Erythrocyte viscosity was greater (p <
      .01) and deformability less (p < .01) in septic blood compared with normals.
      Dilution with hydroxyethyl starch increased erythrocyte viscosity as compared
      with saline (p < .01) and albumin (p < .01). Erythrocyte deformability was
      decreased with both hydroxyethyl starch (p < .001) and albumin (p < .05) compared
      with saline. Increased erythrocyte aggregation was also observed with
      hydroxyethyl starch (p < .05) and albumin (NS) in septic cells when compared with
      saline. These data indicate that hydroxyethyl starch increases blood viscosity,
      decreases erythrocyte deformability, and increases erythrocyte aggregation when
      compared with saline. These changes are less significant with albumin. In
      patients with sepsis, these effects may further compromise the already altered
      erythrocyte rheology.

PMID- 9261900
TI  - Role of oxidant stress and iron delocalization in acidosis-induced intestinal
      epithelial hyperpermeability.
AB  - Using Caco-2BBe monolayers as a model of the intestinal epithelium, we tested the
      hypothesis that reactive oxygen metabolites contribute to lactic acid-induced
      hyperpermeability. Compared to monolayers incubated at normal pH (i.e., 7.4)
      monolayers incubated in medium titrated to extracellular pH (pHo) 5.0 with 10 mM
      lactic acid demonstrated increased permeability to both fluorescein sulfonic acid
      (FS) and fluorescein isothiocyanate-dextran (average molecular mass = 4000 Da;
      FD4). Lactic acid-induced hyperpermeability to both FS and FD4 was reduced by
      adding either 30 microM EUK-8, a superoxide dismutase/catalase mimetic, or
      catalase (10(4) U/mL). Incubation of monolayers with lactic acid increased
      cellular malondialdehyde content, a measure of lipid peroxidation. EUK-8 (30
      microM) completely abrogated this effect. Incubation with ferrous sulfate (100
      microM) exacerbated both lactic acid-induced hyperpermeability to FS and lactic
      acid-induced lipid peroxidation. Iron chelation with 1 mM diethylene triamine
      pentaacetic acid (DTPA)-trisodium calcium salt attenuated lactic acid-induced
      hyperpermeability, whereas iron-loaded DTPA (1 mM) was not protective. Treatment
      with DTPA-trisodium calcium salt also ameliorated lactic acid-induced lipid
      peroxidation. Incubation with lactic acid (pHo 5.0) for 16 h increased the
      cellular content of low molecular weight iron species. Incubation with lactic
      acid (pHo 5.0) for 24 h significantly increased the percentage of oxidized
      protein-bound thiols in Caco-2BBe cells. We conclude that lactic acidosis induces
      hyperpermeability in Caco-2BBe monolayers, in part, via an iron-dependent
      increase in reactive oxygen metabolite-mediated damage.

PMID- 9261901
TI  - Anti-platelet action of nitric oxide and selective phosphodiesterase inhibitors.
AB  - Nitric oxide gas is a potent inhibitor of platelet aggregation, with an IC50 of
      3.6 microM for rabbit platelets. Since the NO effect is mediated via increased
      cGMP, this in vitro study was undertaken to test the hypothesis that selective
      phosphodiesterase (PDE) inhibitors might enhance aggregation inhibition at lower
      NO concentrations. Because the cAMP-selective PDE III and the cGMP-selective PDE
      V are prominent in platelets, milrinone, a PDE III inhibitor, and zaprinast, a
      PDE V inhibitor, were tested alone and in the presence of NO for their effect on
      aggregation. Aggregometry was performed on rabbit platelet-rich plasma following
      addition of ADP as agonist. Milrinone alone gave an IC50 of 12.4 microM. With
      each agent set to give suboptimal inhibition of aggregation, the combination of
      milrinone (3-16 microM) and NO (2-10 microM) produced a greater effect than
      either agent alone. Zaprinast exhibited no effect on aggregation in
      concentrations up to 160 microM. However, adding zaprinast to 2 microM NO, which
      alone reduced aggregation approximately 30%, produced a marked synergism in the
      inhibitory effect up to and including no observable aggregation. These results
      indicate that elevation of either cAMP or cGMP is sufficient to inhibit platelet
      function. The platelet cAMP concentration appears high enough to be inhibitory
      when degradation is suppressed by milrinone. However, basal cGMP levels must be
      increased by NO before the zaprinast effect is observed.

PMID- 9261902
TI  - Requirement for C5a in lung vascular injury following thermal trauma to rat skin.
AB  - Previous studies in rats have shown that deep second degree dermal burns,
      involving 28-30% of total body surface area, result in systemic complement
      activation, appearance in plasma of chemotactic activity, sequestration of blood
      neutrophils in lung capillaries, and development of neutrophil-dependent dermal
      vascular and lung vascular injury. Although blockade of complement activation or
      depletion of complement before skin burns has resulted in significant attenuation
      of tissue injury both locally and distally (in lung), a role for C5a in these
      events is unclear. In the following studies, we demonstrate the presence of C5a
      and neutrophil chemotactic activity in serum and in lung homogenates after
      thermal injury. C5a has also been found in bronchoalveolar lavage fluids of
      thermally injured animals. Treatment of animals with a polyclonal neutralizing
      rabbit antibody to rat C5a was lung protective. The protective effects of the
      antibody (anti-C5a) were associated with diminished vascular permeability
      changes, as well as reduced tissue build-up of myeloperoxidase. Anti-C5a also
      prevented up-regulation of lung vascular ICAM-1 (intercellular adhesion molecule
      1) in skin-burned rats. These observations indicate that C5a is essential for
      development of neutrophil accumulation and vascular permeability increases in
      distant (lung) organs after thermal trauma to skin. The protective effects of
      anti-C5a in lung, appear to be related to prevention of up-regulation of vascular
      ICAM-1. Accordingly, C5a may represent a target for clinical approaches in the
      treatment of organ injury following thermal trauma.

PMID- 9261903
TI  - Interactions of neutrophils and endothelial cells under low flow conditions in
      vitro.
AB  - The interactions of polymorphonuclear leukocytes (PMN) and endothelial cells are
      modulated by adhesion molecules, inflammatory cytokines, and shear stress. We
      investigated the changes in PMN-endothelial cell interactions induced by
      interleukin (IL)-1 beta under low flow conditions. PMN were isolated from the
      venous blood of healthy adults, and endothelial cells were obtained from human
      umbilical veins. The number of PMN that adhered to the endothelial cells
      monolayer that was treated with IL-1 increased significantly at shear stresses
      from .5 to 4.0 dyn/cm2 as compared with untreated endothelial cells. Anti
      intercellular adhesion molecule (ICAM)-1 monoclonal antibody (mAb), anti-E
      selectin mAb, and anti-CD18 mAb each significantly inhibited the increase in PMN
      adherence induced by IL-1 at a low shear stress (1.0 dyn/cm2). Anti-CD18 mAb
      significantly reduced the number of PMN that migrated through the endothelial
      monolayer by blocking the adherence of PMN to the luminal surface of the
      endothelial cells, as well as their transendothelial migration. In contrast, anti
      ICAM-1 and anti-E-selectin mAb each reduced the number of PMN that migrated by
      reducing the number of PMN that adhered to the luminal surface without
      significantly influencing the percent of the adherent PMN that had migrated.
      Although anti-L-selectin mAb reduced the adherence and migration of PMN, these
      effects were not statistically significant. These results indicated that under
      low flow conditions, as well as in the nonflow state, PMN-endothelial cell
      interactions were elicited via CD11/CD18 and ICAM-1 without the involvement of
      selectins.

PMID- 9261904
TI  - Inhalation injury increases the anastomotic bronchial blood flow in the pouch
      model of the left ovine lung.
AB  - Pulmonary parenchymal damage often occurs after airway injury. Bronchial venous
      drainage empties into the pulmonary microvasculature. We developed an in vivo
      model to study the bronchopulmonary portal system after smoke inhalation injury.
      Eight ewes were instrumented with hydraulic occluders on the left pulmonary
      artery (LPA), the left pulmonary vein, and the bronchoesophageal artery (BEA); a
      catheter in the LPA; and Swan-Ganz and femoral artery catheters. The vasculature
      between the occluders was defined as pouch. At stable mean arterial and right
      pulmonary arterial pressures, LPA occlusion reduced the left pulmonary artery
      pressure (LPAP) from 17 +/- 1 mmHg to 8 +/- 1 mmHg (p < .05). After left
      pulmonary vein occlusion, LPAP rose to 28 +/- 4 mmHg (p < .05 vs. baseline),
      indicating that systemic blood had entered the pouch. Opening the pouch to
      atmospheric pressure revealed an anastomotic bronchial blood flow (anastomotic
      Qbr) of .76 +/- .11% of cardiac output (CO). BEA occlusion reduced the
      anastomotic Qbr to .32 +/- .06% of CO (p < .05). Smoke inhalation injury resulted
      in a further increase in the maximal LPAP to 38 +/- 5 mmHg (p < .05 vs. right
      pulmonary artery pressure). The anastomotic Qbr rose to 1.29 +/- .13% of CO (p <
      .05) and was reduced to .40 +/- .09% of CO (p < .05) by BEA occlusion. Inhalation
      injury increased the anastomotic Qbr mainly due to BEA vasodilatation. Because
      the BEA supplies the injured airway, it may deliver deleterious material to the
      lung parenchyma.

PMID- 9261905
TI  - Nitric oxide in the brain increases during a short period of hemorrhagic shock in
      the rabbit.
AB  - We investigated the changes in nitric oxide (NO) concentration in the brain of
      the rabbit by measuring NO-related electrical current. Seventeen Japanese white
      rabbits were anesthetized with pentobarbital sodium and mechanically ventilated
      with tracheotomy tubes. An NO-selective electrode was used for the detection of
      NO. After a round craniotomy in the left parietal lobe, an NO-sensitive electrode
      was placed in the brain. Rabbits were hemorrhaged to a mean arterial blood
      pressure of 35 +/- 7 mmHg, from a baseline of 112 +/- 12 mmHg (mean +/- SD). The
      shock was maintained for 5 min. The mean extracted blood volume was 77 +/- 17 mL.
      Then, retransfusion of shed blood caused a rapid restoration of mean arterial
      blood pressure. The amount of time required to induce hemorrhagic shock was 261
      +/- 34 s. The time required to retransfuse the extracted blood was 233 +/- 43 s
      (p > .05). During shock, the NO-selective electrode produced an extensive
      increase in current, from 110 +/- 94.5 pA to 1010 +/- 543 pA (mean +/- SD, p <
      .001). The current continued to increase for a few minutes after the recovery
      from shock, with a maximal increase reaching 1245 +/- 515 pA (p < .001). This
      enhanced release of NO-related current (1,132%) recovered to the baseline level
      at 44 +/- 7 min after retransfusion. When the same investigation was performed on
      the same animals on which had been placed the same electrode pretreated with NG
      nitro-L-arginine methylester (L-NAME) 30 mg/kg intravenously, NO-related current
      increased from 101 +/- 158 to a maximum of 860 +/- 406 pA (752%). Our results
      suggest that NO may play an important role in the brain during the early period
      of hemorrhagic shock, and that L-NAME 30 mg/kg intravenously might not inhibit
      the NO production in the parietal lobe, probably due to a blood-brain barrier to
      the nitric oxide synthase-inhibiting drug.

PMID- 9261906
TI  - Glucocorticoid regulation of hepatic TNF production following cecal ligation and
      puncture sepsis.
AB  - Tumor necrosis factor-alpha (TNF) is a critical early mediator in the genesis of
      a systemic inflammatory response during a septic insult. Many of the harmful
      effects evident during sepsis are ascribed to excessive endogenous TNF
      production. Because the liver is an important source of circulating TNF during
      endotoxicosis, and because glucocorticoids are believed to have a regulatory role
      in suppressing endogenous TNF production, we evaluated the effect of
      adrenalectomy on the hepatic production of TNF in an isolated perfused liver
      model after cecal ligation and puncture (CLP) sepsis. Fasted, male Holtzman rats
      (n = 4/group) underwent CLP alone, adrenalectomy (ADREX) alone, or CLP plus ADREX
      (CLP/ADREX). Two hours after the operation, the rat livers were explanted and
      perfused in an isolated recirculating model. Serum TNF levels were greater in
      CLP/ADREX rats than in both other groups. TNF production in the perfused liver
      was greater in the CLP/ADREX rats when compared with either CLP alone or ADREX
      alone. A separate mortality study was performed (N = 35) that demonstrated a CLP
      induced mortality of 45%, and a CLP/ADREX mortality of 100%. Thus, adrenalectomy
      increased circulating TNF and hepatic TNF production as well as mortality in CLP
      sepsis. These findings suggest an important role for endogenous glucocorticoids
      in modulating hepatic TNF production during CLP-induced sepsis.

PMID- 9261907
TI  - The adrenal response to sepsis.

PMID- 9261908
TI  - An inhibitor of poly(adenosine 5'-diphosphoribose) synthetase, 3-aminobenzamide,
      does not improve cardiovascular depression, bronchospasm, or survival associated
      with systemic anaphylaxis in rabbits in vivo.
AB  - We investigated whether an inhibitor of poly(adenosine 5'-diphosphoribose)
      synthetase (PARS) is beneficial in anaphylaxis. Twenty-eight rabbits were
      randomly allocated to three groups: Group I (control) received .9% NaCl solution
      10 min before antigen challenge followed by the infusion of the same solution.
      Group II (3-aminobenzamide 20 mg.kg-1) received 20 mg.kg-1 of 3-aminobenzamide (a
      PARS inhibitor) 10 min before antigen challenge followed by the continuous
      infusion of 20 mg.kg-1 of 3-aminobenzamide. Group III received 40 mg.kg-1 10 min
      before antigen challenge followed by the continuous infusion of 20 mg.kg-1 of 3
      aminobenzamide. Survival were similar between three groups. Heart rate, mean
      arterial pressure (MAP), central various pressure, and pulmonary resistance did
      not differ between three groups. Dynamic pulmonary compliance did not differ in
      the early phase after the antigen challenge; however, it was significantly lower
      in Group III than in Groups I and II 15 min after the initiation of anaphylaxis.
      3-aminobenzamide per se did not affect heart rate, MAP, central venous pressure,
      pulmonary resistance, or dynamic pulmonary compliance in animals without systemic
      anaphylaxis. In conclusion, this PARS inhibitor did not improve cardiovascular
      depression or bronchospasm in the early phase of systemic aggregated anaphylaxis
      in rabbits in vivo, implying that the pathophysiological changes associated with
      systemic anaphylaxis may not be related to activation of an energy-consuming DNA
      repair cycle triggered by PARS.

PMID- 9261909
TI  - Nitric oxide, perioxynitrite and poly(ADP-ribose) synthetase in anaphylactic
      shock.

PMID- 9261910
TI  - Regression towards the mean, historically considered.
AB  - The simple yet subtle concept of regression towards the mean is reviewed
      historically. Verbal, geometric, and mathematical expressions of the concept date
      to the discoverer of the concept, Francis Galton. That discovery and subsequent
      understanding (and misunderstanding) of the concept are surveyed.

PMID- 9261911
TI  - The impact and implication of regression to the mean on the design and analysis
      of medical investigations.
AB  - We have examined the regression effect and its magnitude under the Gaussian
      distributional assumption. The impact and implication of regression to the mean
      on the analysis of medical investigations was discussed. For simplicity, we
      called the approach adjusting for the regression effect a two-stage procedure and
      noted its relationship to the analysis of covariance model for comparing
      treatment groups. We also proposed to examine the correlation structure among
      repeated measurements in the absence of any external interventions through a
      model more realistic than the one assuming equal correlations. The proposed
      structure led us to investigate ways to reduce or eliminate regression effect via
      study designs when patient selection is inevitable. Two examples were given to
      help illustrate the discussion in this paper.

PMID- 9261913
TI  - Non-normal variation and regression to the mean.
AB  - Non-normal variation across repeated measurements leads to nonlinear and
      heteroskedastic regression to the mean unlike the simple linear and homoskedastic
      regression to the mean found in normal models. This paper investigates the nature
      of the regression to the mean phenomenon in non-normal settings using (a) small
      variance approximations and (b) exact results obtained using normal mixtures to
      approximate non-normal distributions.

PMID- 9261912
TI  - Adjusting for regression toward the mean when variables are normally distributed.
AB  - Many studies use the same variable, for example blood pressure in studies of
      antihypertensive treatments, to identify subjects to be included in the study and
      to evaluate the effects of a treatment. As a consequence, if not properly
      accounted for, the effect of regression toward the mean can confound the
      evaluation of treatment effects if the study has no randomized control group. In
      this paper we review the methods that have been proposed for adjusting for the
      effect of regression toward the mean when the variable of interest is assumed to
      be normally distributed. Maximum likelihood estimation and moment-based
      estimation are considered, including more recent methods which can be applied
      when repeated measurements on each subject are available.

PMID- 9261914
TI  - Using regression models for prediction: shrinkage and regression to the mean.
AB  - The use of a fitted regression model in predicting future cases, either as a
      diagnostic tool or as an instrument for risk assessment is discussed. The
      regression to the mean effect implies that the future values of the response
      variable tend to be closer to the overall mean than might be expected from the
      predicted values. The extent of this shrinkage is studied for multiple and
      logistic regression models, and is found to be related to simple goodness-of-fit
      statistics of the original regression. Shrinkage is a particularly serious
      problem if the sample size is small and/or the number of covariates is large.
      Shrinkage of predictors is illustrated by two examples. A more general
      formulation is suggested.

PMID- 9261915
TI  - The Sonda Project: prevention, prediction, and psychological disorder.
AB  - The Sonda Project began in Italy in 1985 and was created by Semeion Research
      Center of Sciences of Communication. It has been operating in approximately 30
      Italian cities, ranging from large to small, since 1986. The aim of the Sonda
      Project is to undertake primary prevention measures at the level of personality
      organization disorder. Cognitive and communication disorders are, in the context
      of the Sonda Project, the common ground for many expressions of cultural
      disorders labeled drug addiction, alcoholism, violence, etc. From the point of
      view of the Sonda Project, measures aimed at combating drug-addiction and
      alcoholism are no more than superficial strategies incapable of dealing with the
      causes of self and hetero-destruction (of others). Such abuses are the most
      evident political symptoms. The methodological aim of the Sonda Project,
      therefore, consists in understanding, predicting, and acting upon the incubation
      disorder of human beings; a disorder which subsequently transforms itself into
      more or less recognizable symptoms. In order to attain its aim, the Sonda Project
      has made use of two instruments: 1) a series of Intelligent Computerized
      Observatories, able to predict, in each community, the typology of people who are
      more likely to exhibit forms of destructive suffering; 2) a local team able to
      use such advanced technology and able to utilize territorial activation
      techniques. These are designed to reinsert into the arena of the social game
      those people who are more "at risk" in terms of self and heterodestruction, and
      who are most exposed to psychological and sociological levels of relational
      "fatigue."

PMID- 9261916
TI  - Ethnography: an overview.
AB  - This article offers an overview of ethnographic research. First, an example from
      a "traditional" ethnography is presented to make explicit some key aspects of the
      research process and the underlying logic of ethnography's "abductive"
      epistemology. Next, ethnography is contrasted and compared with the "received
      view" (deductive, quantitative) to show how it differs from the usual tradition
      of "social research." Finally, the way that ethnography and epidemiology are
      being combined in United States drug use(r) research is described.

PMID- 9261917
TI  - Toward a theory of social pharmacology: the actor-spectator paradox applied to
      the psychotropic prescribing process.
AB  - Traditionally, drug prescribing was regarded as part of the physician's decision
      making role. However, recently it has been recognized that such a perspective is
      insufficient to understand the psychotropic prescribing process. To understand
      this process, a drug communication perspective is necessary. This article
      describes the actor-spectator paradox and its influence on drug communication and
      psychotropic drug prescribing. The actor-spectator paradox postulates that the
      actor and the spectator have divergent perspectives about the cause of the
      actor's behavior. The spectator makes assumptions about the actor's cognitive
      system other than the actor herself is making. This difference is often the basis
      for misunderstandings between a health professional and a patient. If a health
      professional can learn to make more realistic assumptions about a patient's
      cognitive system, communication between the two will improve. In the same way a
      patient has to learn to make more realistic assumptions about the cognitive
      systems of health professionals. The actor-spectator paradox can be applied to
      different areas of Social Pharmacology such as the diagnosis of patients
      suffering from mental health problems, drug compliance, informed consent, and the
      prescribing of psychotropics.

PMID- 9261918
TI  - Modified therapeutic community for mentally ill chemical "abusers": background;
      influences; program description; preliminary findings.
AB  - This paper briefly surveys the literature that addresses the problem of co
      occurring mental and "substance abuse disorders." It discusses several convergent
      influences on the development of modified therapeutic community (TC) approaches.
      The paper describes in some detail the modified TC program for mentally ill
      chemical "abusers" (MICAs). The paper also summarizes research data that
      establish positive retention rates and significant in-treatment change to support
      the effectiveness of the modified TC and to underscore the limited effect of
      treatment-as-usual approaches. Treatment approaches must be comprehensive,
      multidimensional, of relatively long duration, and must systematically address
      the interrelated problems of mental illness and substance use.

PMID- 9261919
TI  - Modulating effects of flavonoids on food mutagens in human blood and sperm
      samples in the comet assay.
AB  - The flavonoids silymarin, myricetin, quercetin, kaempferol, rutin, and kaempferol
      3-rutinoside have been examined in combination with the food mutagens 3-amino-1
      methyl-5H-pyrido (4,3-b)indole (Trp) and 2-amino-3-methylimidazo-4,5-f)quinoline
      (IQ) in the Comet assay in human lymphocytes from donors A and B and human sperm
      from donor B. These compounds alone have been shown to produce positive responses
      in the Comet assay, as have the food mutagens. However, in combination with the
      food mutagens, the flavonoids produced antigenotoxic effects since DNA damage was
      reduced in the Comet assay in human lymphocytes and sperm over a similar dose
      range in the absence of metabolic activation. Only quercetin and kaempferol were
      examined in blood with metabolic activation, but there was no difference in
      response to that obtained without activation. In the blood there was an
      exacerbation or synergy of response at the lowest doses of the flavonoids. In the
      sperm this was also the case with silymarin and myricetin. With kaempferol there
      was no antigenotoxic effect and quercetin protected below baseline levels. Since
      the effects were observed in lymphocytes and sperm over a similar dose range, it
      would suggest that the Comet assay responses occur in somatic and germ cells in a
      one-to-one ratio. These results have implications for man in terms of risk
      assessment and in the modulation of isolated food constituents.

PMID- 9261920
TI  - Detection of fragile sites induced by pyrimethamine.
AB  - In this study, the effect of pyrimethamine in inducing expression of fragile
      sites in human peripheral blood lymphocyte cultures is investigated. In vitro
      lymphocyte cultures of 15 healthy individuals were treated with 0.02 mg/ml of
      pyrimethamine for 48 and 72 hr. One culture was used as control. The number of
      cells showing chromosomal aberration increases significantly in the cultures
      after 48 and 72 hr in comparison to the control group (P < 0.001). Localization
      of fragile sites was determined by the G-banding method and light microscopy. As
      a result, five folic acid-sensitive fragile sites (1p32, 1q32, 3p14, 6p22, 14q24)
      were detected.

PMID- 9261921
TI  - Dimethylarsinic acid treatment alters six different rat biochemical parameters:
      relevance to arsenic carcinogenesis.
AB  - In a previous study, we found that sodium arsenite increased hepatic ornithine
      decarboxylase (ODC) activity and hepatic heme oxygenase (HO) activity, but did
      not cause any DNA damage in adult female rat liver or lung, suggesting that
      arsenite may be a promoter of carcinogenesis. In this study sodium arsenate,
      monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) were administered
      orally in equitoxic doses to adult female rats at 21 and 4 h prior to sacrifice.
      DNA damage (DD), cytochrome P450 content (P450), glutathione content (GSH), ODC,
      serum alanine aminotransferase (ALT) and HO were measured in liver and/or lung
      tissue. At 60 mg/kg in rat liver, sodium arsenate increased hepatic HO fivefold.
      MMA decreased ALT at 226 mg/kg, decreased ALT and GSH at 679 mg/kg and also
      increased P450 at 679 mg/kg in rat liver. DMA decreased ALT and hepatic GSH and
      increased hepatic HO at 387 mg/kg. In the lung, DMA decreased ODC at both 129 and
      387 mg/kg. DD in lung tissue was significantly higher at 387 mg/kg DMA,
      demonstrating organ specific DNA damage. The biochemical effects and the inferred
      oncologic potential of the four major forms of arsenic (arsenate, arsenite, MMA
      and DMA) differ dramatically. The inorganic forms (arsenate and arsenite) are
      similar to each other (both good HO inducers); the methylated organic forms of
      arsenic (MMA and DMA) also share a similar pattern of biochemical effects
      (decreased GSH and ALT, increased P450). All six of the biochemical parameters
      studied were altered by DMA in either rat liver or lung.

PMID- 9261922
TI  - Mutagenic and cytotoxic activity of an isocoumarin (Paepalantine) isolated from
      Paepalanthus vellozioides.
AB  - A new isocoumarin with antimicrobial activity was isolated from Paepalanthus
      vellozioides (a native Brazilian plant) and called paepalantine. This study was
      carried out to assess the mutagenic activity of this new agent in assays with
      Salmonella typhimurium TA100, TA98, and TA102 and in Chinese hamster ovary (CHO)
      cell cultures, as well as cytotoxicity to McCoy cells. paepalantine caused a
      significant dose-dependent increase in the frequency of revertants in the three
      strains used in the assay, both with and without S9 mix, in concentrations
      varying from 2 to 128 micrograms/plate. The mutagenicity was confirmed in assays
      with CHO cells treated in the G1, S, and G2 phases of the cell cycle. There was
      an increase in the chromosomal aberration frequency, mainly in the G2 phase.
      Furthermore, the mitotic index of the treated cultures (40,80, and 160
      micrograms/ml) was significantly lower, indicating cytotoxicity. The midpoint
      cytotoxicity values of McCoy cells by the neutral red (NR) and microculture
      tetrazolium (MTT) techniques resulted in a NR50 and MTT50 of 30 and 38
      micrograms/ml, respectively. Alterations to the paepalantine structure are
      suggested to reduce its mutagenic and cytotoxic activity in investigations for
      its antineoplastic potential.

PMID- 9261923
TI  - First 25 years of the Hungarian congenital abnormality registry.
AB  - The Hungarian Congenital Abnormality Registry was established in 1962 based on
      obligatory notification of cases with congenital abnormalities by physicians.
      However, continuous and expert evaluation of data started in 1970 when the
      Registry was moved to the National Institute of Public Health. Later several
      other systems, including the Nationwide Evaluation of Multimalformed Infants,
      Case-Control Surveillance of Congenital Abnormalities, and Surveillance of
      Germinal Mutations, were based on the Registry. Data and results of the first 25
      years of the Registry are evaluated from three different aspects: 1) evaluation
      of the originally planned and later adopted missions of the Registry; 2) quality
      control of the Registry is based on the proportion of misdiagnoses, completeness
      of notifications, and pathogenetically oriented classification; 3) outcome
      evaluation indicated the different quality of recorded data in lethal, severe,
      and mild congenital abnormalities. The data base of the Registry was appropriate
      to estimate the proportion of preventable congenital abnormalities due to the
      four different preventive programs and to evaluate the pregnancy outcomes after
      the Chernobyl nuclear power plant accident.

PMID- 9261924
TI  - Effect of multifactorial genetic liability to exencephaly on the teratogenic
      effect of valproic acid in mice.
AB  - The present study shows that the multifactorial genetic liability to spontaneous
      exencephaly in the SELH/Bc mouse strain (10-20% of embryos) also confers an
      elevated risk of exencephaly induced by valproic acid. Treatment of pregnant dams
      (600 mg/kg sodium valproate in distilled water, i.p.) during the critical period
      on day 8 (D8) of gestation resulted in D14 exencephaly frequencies of 69% in
      SELH/Bc contrasted with 39% in each of the SWV/Bc and ICR/Bc strains. Analysis of
      these data under the assumptions of the threshold model indicated that the
      valproic acid-induced-shift in mean liability was similar for all three strains,
      and therefore the effects of genotype and teratogen were additive, not
      synergistic. A similar exencephaly response pattern for the same three strains
      was observed previously with retinoic acid [Tom et al. (1991) Teratology 43:27
      40], a pattern that, combined with the data of Finnell et al. [(1988) Teratology
      38:313-320], argues that strain differences in exencephaly response are not due
      to strain differences in teratogen metabolism. SWV/Bc and ICR/Bc embryos differ
      in location of the Closure 2 initiation site of cranial neural tube closure
      [Juriloff et al. (1991) Teratology 44:225-233], but the observation that they do
      not differ in risk of exencephaly produced by either valproic acid or retinoic
      acid contradicts the hypothesis that this particular morphological difference
      underlies strain differences in exencephaly risk. The high exencephaly response
      of SELH/Bc to two teratogens predicts that human conceptuses with a genetically
      determined elevated risk for neural tube defects could be easily tipped into high
      risk by mild teratogens.

PMID- 9261925
TI  - Stereoselective dysmorphogenicity of the enantiomers of the valproic acid
      analogue 2-N-propyl-4-pentynoic acid (4-yn-VPA): cross-species evaluation in
      whole embryo culture.
AB  - We previously reported the in vitro differential stereoselective dysmorphogenic
      potential of the R(+) and S(-) enantiomers of 2n-propyl-4-pentynoic acid (4-yn
      VPA) in mice. To determine whether this stereoselectivity is species specific, we
      evaluated the dysmorphogenic potential of these isomers as well as valproic acid
      (VPA) to gestational day 9 rat embryos using whole embryo culture (WEC). Aqueous
      solutions of the sodium salts of R-4-yn-VPA, S-4-yn-VPA, 50%R/ 50%S-4-yn-VPA or
      VPA were added to the culture medium to give 0, 0.075, 0.15, 0.3, 0.6, or 1.2
      mmol/L and embryos were evaluated 48 hr later. The S-4-yn-VPA enantiomer gave
      clear concentration-dependent dysmorphology as well as effects on developmental
      score, somite number, crown rump length, and head length. Effects on rotation and
      defects of the neural tube, somites and heart were observed. Embryolethality was
      observed only at 1.2 mmol/L concentration. The R-4-yn-VPA enantiomer was neither
      embryo toxic nor dysmorphogenic at any concentration. VPA significantly reduced
      all parameters and was dysmorphogenic at the highest concentration but was not
      embryo lethal. The 50/50 mixture of R- and S-isomers appeared to elicit a degree
      of embryolethality and dysmorphology similar to VPA. The potency order for the
      four chemicals was S(-) > S(-)/R(+) = VPA > > > R(+), comparable to that observed
      in mice by either in vivo or in vitro exposure. These data demonstrate that the
      stereoselective dysmorphology for these enantiomers can be observed across
      species and is not related to maternal metabolism.

PMID- 9261926
TI  - Minor malformations and physical measurements in autism: data from Nova Scotia.
AB  - In the context of an epidemiological study of autism in Nova Scotia, subjects
      were evaluated for minor physical anomalies and physical measurements. Normal
      control children, children with autism and their siblings, and children with
      developmental disabilities and their siblings were compared. Posterior rotation
      of the external ears was found to be a characteristic related to autism
      specifically, rather than to developmental disabilities in general. Small feet
      and normal-to-large hands also were observed in the autism group. Children with
      autism had a significant reduction in interpupillary distance, but not
      intercanthic distance or head circumference. In contrast, children with other
      developmental disabilities were notable for general small stature, which affected
      the hands, feet, eyes, and head size, as well as height. Abnormal ear
      configuration was the minor malformation most characteristic of the developmental
      disability group, and the subset of Down syndrome children had single transverse
      creases of the palm and epicanthic folds that resulted in significantly increased
      rates of these anomalies in the developmentally disabled controls. Siblings of
      the two disabled groups were not significantly different from normal controls on
      any of the measures that characterized children with autism or other
      developmental disabilities. The results agree with those of several previous
      studies, which have suggested that abnormalities of the ears are the general
      category of minor anomalies most associated with autism. Recent evidence
      regarding the embryological origin of autism suggests that the ear effects may be
      an important marker of the initiating events that lead to the disorder.

PMID- 9261927
TI  - Effects of TCDD on Ah receptor, ARNT, EGF, and TGF-alpha expression in embryonic
      mouse urinary tract.
AB  - Prenatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces
      hydronephrosis in C57BL/6N mice. The etiology of this response involves TCDD
      induced hyperplasia of ureteric epithelium, which occludes the ureteric lumen,
      blocking the flow of urine. The present study localizes and examines the effects
      of TCDD on the expression of the Ah receptor (AhR), the Ah receptor nuclear
      translocator (ARNT), epidermal growth factor (EGF), and transforming growth
      factor-alpha (TGF-alpha) in the epithelial cells of the developing urinary tract,
      particularly the ureteric bud derivatives (ureter and tubules). Pregnant C57BL/6N
      mice were dosed on gestation day (GD) 10 with either corn oil or TCDD at 12
      micrograms/kg; a dose of 24 micrograms/kg is expected to induce 100%
      hydronephrosis. The metanephric urinary tract is morphologically detectable as
      early as GD 12; thus, embryos were removed on GD 12, 13, and 14, and the lower
      dorsal torso was prepared for immunohistochemistry or in situ hybridization.
      Regardless of treatment, the expression of both AhR and ARNT increased in
      epithelial cells of the ureter and AhR increased in the metanephric tubules from
      GD 12-14. In situ hybridization localized the expression of AhR and ARNT mRNAs to
      these derivatives of the ureteric bud and levels of mRNA increased throughout the
      developmental period examined. There were no significant effects of TCDD
      treatment on expression of AhR, while TCDD significantly decreased levels of ARNT
      in tubules on GD 14. The epithelial cells of the ureter and tubules expressed TGF
      alpha and EGF. EGF increased from GD 12 to 13 in the tubules and ureter, but
      there was no difference from GD 13 to 14. Treatment with TCDD reduced TGF-alpha
      significantly only in tubules on GD 13. TCDD exposure significantly decreased EGF
      in ureter and tubule cells on both GD 13 and 14. In summary, the epithelial cells
      of the embryonic mouse urinary tract expressed AhR, ARNT, EGF, and TGF-alpha in
      developmentally dependent patterns. These proteins are involved in the regulation
      of embryonic cell proliferation during normal urinary tract development and are
      probably involved in the hyperplastic response to TCDD.

PMID- 9261928
TI  - Teratogen update: polychlorinated biphenyls.

PMID- 9261929
TI  - Comparative effects of lingual and facial nerve stimulation on intracranial and
      extracranial vasomotor responses in anesthetized cats.
AB  - Electrical stimulation of the central cut end of the lingual nerve (as reflex
      activation of parasympathetic nerve) or of the peripheral cut end of the facial
      (VIIth cranial) nerve (as direct activation of parasympathetic nerve) elicited
      the ipsilateral blood flow increases in lower lip, palate and common carotid
      artery (CCA) but not in frontal cerebral cortex in alpha-chloralose-urethane
      anesthetized, vago-sympathectomized cats. No significant difference, in terms of
      the vasomotor changes examined, was found between lingual nerve and facial nerve
      stimulation. The results suggest that there is no somato-parasympathetic reflex
      vasodilator mechanism serving the frontal cerebral cortex, and that changes in
      CCA blood flow should not be taken to be indicative of blood flow changes in
      cerebrocortical blood flow. However, we cannot entirely rule out the possibility
      of a neurogenic vasodilator influence of the facial pathway, since small blood
      flow increases in the frontal cerebral cortex were sometimes observed on facial
      nerve stimulation.

PMID- 9261930
TI  - Effects of long-term low-dose macrolide administration on neutrophil recruitment
      and IL-8 in the nasal discharge of chronic sinusitis patients.
AB  - Effects of long-term low-dose macrolide administration were studied in patients
      with chronic sinusitis. Twelve patients with non-allergic chronic sinusitis were
      orally given 150 mg roxithromycin once a day without other treatments. The
      patients underwent computed tomography before and after the treatment, and
      paranasal sinus aeration was analyzed quantitatively. The number of neutrophils
      in the nasal smear was semiquantitatively assessed on a grading scale, and the IL
      8 concentration in the nasal discharge was measured by enzyme immunoassay. The
      aeration of all four sinuses significantly improved, and recruited neutrophils
      and the IL-8 level in the nasal discharge were simultaneously reduced after the
      treatment. These findings suggest that long-term low-dose roxithromycin
      administration inhibits the positive feedback mechanism of neutrophil recruitment
      and IL-8 production by the recruited neutrophils, which is considered to be an
      essential cause of the prolongation of sinusitis.

PMID- 9261931
TI  - Myocardial glucose metabolism is different between hypertrophic cardiomyopathy
      and hypertensive heart disease associated with asymmetrical septal hypertrophy.
AB  - Myocardial glucose metabolism has been shown to be heterogeneous in patients with
      hypertrophic cardiomyopathy (HCM). We tested the hypothesis that myocardial
      glucose metabolism differs between patients with HCM and those with hypertensive
      heart disease (HHD) associated with asymmetrical septal hypertrophy. We studied
      12 patients with HCM, 7 HHD patients associated with asymmetrical septal
      hypertrophy using 18F 2-deoxyglucose (FDG) and positron emission tomography. We
      calculated % FDG fractional uptake in the inter-ventricular septum and
      posterolateral wall. Heterogeneity of FDG uptake was evaluated by % interregional
      coefficient of variation of FDG fractional uptake in each wall segment. In both
      the interventricular septum and posterolateral wall, % FDG fractional uptake was
      not significantly different between the two groups. The % interregional
      coefficient of variation for both interventricular septum (10.6 +/- 1.6 vs. 4.1
      +/- 0.5, p < 0.01) and posterolateral wall (5.9 +/- 0.7 vs. 3.8 +/- 0.5, p <
      0.05) was significantly larger in patients with HCM than in HHD patients
      associated with asymmetrical septal hypertrophy. Echocardiography demonstrated
      that the degree of asymmetrical septal hypertrophy was similar between the two
      groups. These results suggest that myocardial glucose metabolism may be more
      heterogeneous in patients with HCM compared to HHD patients associated with
      asymmetrical septal hypertrophy, although the left ventricular shape is similar.
      The difference in the heterogeneity might have resulted from differences in the
      pathogeneses of the two diseases.

PMID- 9261932
TI  - A possible use of color Doppler flow imaging in predicting the cause of bladder
      hypertrophy.
AB  - The present study was designed to test the predictability of color Doppler flow
      imaging of the bladder in determining the cause of bladder hypertrophy. The blood
      flow in the anterior bladder wall was measured in 35 patients with an abnormally
      increased ultrasound estimated bladder weight (UEBW) of more than 35.0 g. Of
      these, 18 were diagnosed as having infravesical obstruction due to benign
      prostatic hyperplasia (obstructive group). The remaining 17 were diagnosed as
      having neurogenic bladder dysfunction (NB group). Scanning to detect blood flow
      was continued for 5 minutes, the bladder having been filled with 100 ml of
      saline. Blood flow was detected in 83.3% (15/18) of the obstructive group,
      compared to 23.5% (4/17) in the NB group (p < 0.001). Infravesical obstruction
      was detected with a diagnostic accuracy of 80.0% (28/35) by color Doppler flow
      imaging. Color Doppler flow imaging was useful in predicting the cause of bladder
      hypertrophy in patients with abnormally increased UEBW.

PMID- 9261933
TI  - Angiotensin converting enzyme gene polymorphism and its enzyme activity in serum
      in young Japanese females.
AB  - To assess the potential association between the angiotensin converting enzyme
      (ACE) gene polymorphism and the activity of the renin-angiotensin system in a
      Japanese population, we determined the ACE genotype and its enzyme activity in
      serum in 108 young Japanese females. Genomic DNA was extracted from blood samples
      and amplified by polymerase chain reaction (PCR). PCR primers flanked the
      polymorphic region in intron 16 of the ACE gene. The distribution of the DD, ID
      and II ACE genotypes was 10, 55 and 35%, respectively. The estimated allele
      frequencies of the deletion and the insertion were 0.375 and 0.625, respectively.
      The mean serum ACE activity in DD subjects was about 1.4 times that of II
      subjects (p < 0.01), with ID subjects having intermediate levels (p < 0.05),
      whereas the renin profile were not statistically different among the three
      groups. These results indicate a significant association between ACE gene
      polymorphism and serum ACE activity levels, suggesting a mechanism by which
      genotype might have a hearing on the physiology of the renin-angiotensin system
      axis.

PMID- 9261934
TI  - Decrease in Thy-1 expression on peripheral CD34 positive cells induced by G-CSF
      mobilization. The Tohoku Children Leukemia Study Group.
AB  - In order to ascertain the cytological features of peripheral hematopoietic
      progenitor cells (PHPC) mobilized after administration of chemotherapeutic agents
      and G-CSF, lineage- and progenitor cell-specific surface markers on CD34 positive
      (+) cells were sequentially examined. Nineteen evaluable samples were obtained
      from a malignant lymphoma, an acute lymphoblastic leukemia and 5 neuroblastoma
      patients. CD38 and HLA-DR were respectively expressed on more than 95% and
      approximately 85% of CD34+ PHPC cells. CD19 was also expressed on the majority
      and CD117 on 10 to 20% of the CD34+ cells. The most striking finding was that the
      Thy-1(CDw90)+/CD34+ population was decreased at the peak of mobilization of CD34+
      cells as compared to the early phase after G-CSF administration (approximately
      20% vs. 60%). These results suggest that decrease in Thy-1 expression on CD34+
      cells is related to mechanisms easing CD34+ cell mobilization to the peripheral
      blood.

PMID- 9261935
TI  - A case of a non-insulin dependent diabetic patient with regular spontaneous
      hypoglycemic attacks, which were due to insulin-binding antibodies induced by
      human insulin therapy.
AB  - A 74-year-old diabetic patient had been treated with oral hypoglycemic agents
      from the age of 40 years until the age of 72, when his treatment regimen was
      changed to human insulin. He began experiencing hypoglycemic attacks 14 months
      after the initiation of insulin therapy. He continued to experience hyperglycemia
      every morning and hypoglycemia every day at 5:30 p.m. even after insulin therapy
      was withdrawn. His plasma levels of C-peptide immunoreactivity, total and free
      immunoreactive insulins were 4.2 ng/ ml, 740 microU/ml and 141.8 microU/ml,
      respectively. His 125I-insulin binding rate was 94.4%. These findings suggest
      that his hypoglycemic attacks may have been due to insulin antibodies. Analysis
      revealed that insulin binding antibodies belonged to IgG with kappa light chains.
      The patient's genotype was HLA-DR4. He had not received animal insulin or any
      medications containing a sulfhydryl group. Although the IgG antibody was produced
      against injected human insulin, his HLA type and the characteristics of his
      antibodies resembled those of a patient with insulin autoimmune syndrome (IAS).
      We hypothesize that this patient represented a rare instance of a patient
      constitutionally similar to a patient with IAS, but whose hypoglycemic attacks
      resulted from the antibodies induced by the administration of human insulin. This
      case seems to be the first one with hypoglycemic attacks due to anti-human
      insulin antibody produced by human insulin therapy.

PMID- 9261936
TI  - A case of Marchiafava-Bignami disease with complete recovery: sequential imaging
      documenting improvement of callosal lesions.
AB  - Serial CT and MR imaging findings in a 44-year-old woman with Marchiafava-Bignami
      disease (MBD) are reported. In the acute stage, CT studies disclosed subtle
      hypodensity in the splenium, and T2-weighted MR images revealed apparent high
      signal intensity of the splenium and the central portion of the corpus callosum.
      Treatment with vitamin B complex resulted in complete recovery. T2-weighted MR
      images obtained three weeks after admission revealed dramatic resolution of
      imaging abnormalities, with only faint high signal intensity remaining in the
      splenium. The sequential changes observed on CT and MR images provided early
      diagnosis of MBD and the resolution of the lesion considered as brain edema,
      which suggested that edema might, in addition to demyelination or necrosis, be
      involved in the acute progression of MBD.

PMID- 9261937
TI  - Two-D distance distribution analysis: an application to HBcAg-positive
      hepatocytes and its relation to septum formation in cirrhosis.
AB  - The morphogenesis of cirrhotic septa in chronic hepatitis B was studied assuming
      that they arise at the sites of hepatocellular necrosis invoked by host immune
      reaction against HBcAg-expressing hepatocytes. Sections from three livers with
      chronic hepatitis B, all in cirrhotic stage, were immunostained with HBcAg and
      subjected to morphometry to analyze the distribution of HBcAg(+) hepatocytes and
      its relation with septa. HBcAg(+) cells were not distributed randomly over the
      nodules but forming focal areas. The septum formation along these foci was shown
      by 2-D distance distribution analysis, a technique we devised. Upon a sheet of
      color microphotograph of immunostained section, hundreds of test points each 400
      microns apart were arranged by overlaying a tessellated grid. From each of the
      points hitting the nodules, the distance to the nearest nodulo-septal border
      D(min) was measured. Measurement was performed on a total of 2,585 test points.
      It was shown that the mean D(min) in the HBcAg(+) areas was significantly smaller
      than in HBcAg(-) areas. Thus, the cirrhotic septa are considered to arise at the
      places of HBcAg(+) foci, connecting them by postnecrotic collapsing.

PMID- 9261938
TI  - Innocuity studies of SAG-2 oral rabies vaccine in various Zimbabwean wild non
      target species.
AB  - The SAG-2 modified live rabies vaccine was tested for innocuity when administered
      by the oral route in several potential wild non-target bait-consuming species, as
      follows: ten chacma baboons (Papio ursinus), six African civets (Civettictis
      civetta), six slender mongooses (Galerella sanguinea), six honey badgers
      (Mellivora capensis), six large-spotted genets (Genetta tigrina), 39 multi
      mammate mice (Mastomys natalensis), 26 bushveld gerbils (Tatera leucogaster) and
      six pied crows (Corvus albus). At least 9.0 log10 median tissue culture
      infectious doses (TCID50), given in a volume of 1 ml, was administered orally to
      each of the animals, except the rodents which received 8.0 log10 TCID50, given in
      0.1 ml. All the animals were observed for not < 90 days for signs of vaccine
      induced rabies. Most of the species were also tested for vaccine virus
      replication in the oral cavity and persistent virus infection in the brain,
      salivary gland and tonsil. None of the animals died of rabies and no persistent
      infection was found. Rabies virus which was pathologically and serotypically
      indistinguishable from the vaccinal strain was isolated from the saliva of one
      genet 1 day after vaccine administration. From this study it was concluded that
      SAG-2 rabies vaccine would be safe for use in most situations where oral
      vaccination campaigns for jackals are required in Zimbabwe.

PMID- 9261939
TI  - Further evaluation of the safety and protective efficacy of live attenuated
      hepatitis A vaccine (H2-strain) in humans.
AB  - A study on the possibility of transmission of live hepatitis A vaccine (H2
      strain) from vaccinees to nonvaccinees was conducted. As a result, no
      seroconversion was found among 87 seronegative nonvaccinees, who had a close
      contact with their 141 subcutaneously vaccinated classmates nor was it found
      among 101 seronegative children administered the vaccine orally. The above
      fundings suggest that by losing the ability to be transmitted orally the vaccine
      virus may result in a decreasing possibility of dissemination among contacts. A 4
      year study on the protective efficacy of the H2-strain vaccine was done at 11
      primary schools starting at 1991 in Shaoxing County. Since then, there has been
      no hepatitis A reported among 18102 cumulative person-years in the vaccination
      group, while 495 cases occurred among 242168 cumulative person-years in the
      control groups. A large scale vaccination with a cumulative vaccination coverage
      of 89.45% was carried out in Jiaojiang City among children 1-15 years old.
      Hepatitis A in this age group in the city, which had 12-87 cases per annum with
      an average of 32 for 8 years before vaccination, decreased drastically to 0-1
      cases after vaccination. The protective efficacy of H2-strain vaccine proved to
      be satisfactory.

PMID- 9261940
TI  - Characterization of Schistosoma mansoni 44.7/56.8 kDa egg antigens recognized by
      human monoclonal antibodies which induce protection against experimental
      infection and proliferation of peripheral blood mononuclear cells from
      schistosomiasis patients.
AB  - We described here the characterization of Schistosoma mansoni egg antigens
      recognized by human monoclonal antibodies B10 (HmAb-B10) and D5 (HmAb-D5). SDS
      PAGE and Western blot analysis revealed that these monoclonals recognized two
      antigens of M W 44.7/56.8 kDa, with pI of 7.0 and 7.8, respectively. The passive
      transfer of B10 and D5 induced a significant protection of 48% and 54% in Balbic
      mice. Results of in vitro cytotoxicity assay showed that both monoclonals were
      able to kill schistosomula in the presence of rabbit complement. These
      monoclonals mediated 48% and 74% of schistosomula cytotoxicity, respectively. Egg
      antigens were purified by affinity chromatography using monoclonal antibodies B10
      and D5. Treatment of purified antigens with periodate, galactose oxidase and
      trifluoromethane sulphonic acid did not prevent binding by B10 and D5 in ELISA
      assay. However, the treatment with protease K and 2-mercaptoethanol affects the
      antibodies binding, showing that the HmAbs B10 and D5 recognize polypeptide
      epitopes. Vaccination of mice with these antigens in Freund's adjuvant induced
      43% reduction in worms burden after challenge with S. mansoni cercariae. In vitro
      blastogenesis assays with peripheral blood mononuclear cells from patients
      infected with S. mansoni revealed that purified antigens were able to induce
      significant cell proliferation.

PMID- 9261941
TI  - Relative immunogenicity and efficacy of two synthetic chimeric peptides of
      fimbrin as vaccinogens against nasopharyngeal colonization by nontypeable
      Haemophilus influenzae in the chinchilla.
AB  - The OMP P5-homologous fimbriae of nontypeable Haemophilus influenzae (NTHi) are
      an adhesin and a virulence factor for otitis media in chinchilla models. We
      synthesized two peptides (LB1 and LB2) which incorporate determinants of the
      fimbrial subunit co-linearly synthesized with a "promiscuous" T-cell epitope from
      the fusion protein of measles virus. Sera obtained from immunized rabbits and
      chinchillas demonstrated significant reciprocal titers against both the
      homologous peptide and isolated fimbrial protein. Antisera also immunolabeled
      native fimbriae of whole unfixed NTHi. Immunization with LB1 or fimbrin resulted
      in elimination of NTHi from the chinchilla nasopharynx 2-3 weeks earlier than
      controls, respectively.

PMID- 9261942
TI  - Antibody efficacy as a keen index to evaluate influenza vaccine effectiveness.
AB  - The efficacy of the influenza vaccine is often understimated, due to the dilution
      of the outcome by noninfluenzal illnesses. We thus explored the methodology to
      evaluate the effect of the inactivated influenza vaccine under the following
      strict conditions: an assessment of the effectiveness on clinical illness among
      healthy adults in a small-scale mixed epidemic during the 1991-1992 season. The
      vaccine antigens included were A/Yamagata/32/89 (H1N1), A/Beijing/352/89 (H3N2),
      and B/Bangkok/163/90. Two indices were analyzed: "vaccine efficacy", a comparison
      between the vaccinees and the nonvaccinees; and "antibody efficacy", a comparison
      between those with and those without a protective level of pre-epidemic
      hemagglutination-inhibition (HAI) antibody. The odds ratio (OR) and its 95%
      confidence interval (95% CI) was calculated by the logistic regression model. A
      decrease in the age-adjusted OR of vaccination was not statistically significant:
      0.54 (95% CI: 0.19-1.53) corresponding to vaccine efficacy (1-OR) of 46% (-53% to
      81%). Among the vaccinees, a significantly decreased OR in those with a higher
      titer to A/Beijing was observed: 0.14 (0.02-0.92) adjusted for the mutual effects
      of pre-epidemic antibodies to different vaccine antigens. The adjusted ORs thus
      calculated for A/Yamagata and B/Bangkok were not found to be statistically
      significant. The antibody efficacy (1-OR) was estimated to be 86% (8% to 98%)
      against illnesses related to A/Beijing-like viruses. The product of antibody
      efficacy (86%) and the proportion of those who achieved a protective level of
      antibody after vaccination (73% for A/Beijing strain) was 63%, which is
      theoretically equivalent to the vaccine efficacy. Thus, the antibody efficacy is
      considered to be an important index, while the vaccine efficacy against clinical
      illnesses is easily disturbed by extraneous factors in the field trials.

PMID- 9261943
TI  - Expression of a synthetic pertussis toxin operon in Escherichia coli.
AB  - Bordetella pertussis is the causative agent of whooping cough, a severe disease
      of infants characterised by repeated of paroxysmal coughing. Pertussis toxin (PT)
      is a major virulence factor of B. pertussis and is a typical A/B bacterial toxin
      consisting of five subunits S1-S5 in a ratio of 1:1:1:2:1. The PT subunit genes
      are organized into an operon which is not expressed in Escherichia coli, thus
      hampering the use of this organism for vaccine production. We have expressed the
      five PT subunits individually in E. coli by replacing the wild-type
      transcriptional and translational signals, and in the case of the S4 subunit the
      leader peptide has been exchanged with a modified E. coli beta-lactamase leader
      sequence. We have developed a stepwise cloning method to construct a synthetic PT
      operon which simultaneously expresses the five PT subunits in E. coli. Western
      blot analysis indicated that in E. coli KS476 containing the synthetic PT operon,
      S4 and S5 were completely processed, S1 was partially processed, whilst the
      majority of S2 and S3 remained unprocessed. Periplasmic extracts contained
      soluble S1 and S3; however, the processed form of S2, S4 and S5 were not
      detected, suggesting that these subunits may be membrane associated or in an
      insoluble form. This work should allow an investigation of the potential of E.
      coli to produce detoxified PT in a background free of other pertussis virulence
      factors that may contribute to the side-effects of some vaccine preparations
      currently in use.

PMID- 9261944
TI  - Effect of lipid modification on the physicochemical, structural, antigenic and
      immunoprotective properties of Haemophilus influenzae outer membrane protein P6.
AB  - The outer membrane lipoprotein, P6 of Haemophilus influenzae was studied to
      determine the importance of the native palmitoyl moiety on its physicochemical
      and immunological properties. A recombinant P6 (rP6) molecule devoid of
      lipidation signal sequence was expressed in Escherichia coli and its properties
      were compared to those of the palmitylated protein purified from H. influenzae.
      The isoelectric point of rP6 was more acidic than that of the native protein and
      also exhibited less secondary structure than P6 as judged by circular dichroism.
      However, both forms of P6 induced identical P6-specific antibody titers in guinea
      pigs when Freund's adjuvant was used. These antisera reacted with a panel of
      overlapping P6 peptides in a comparable manner and in addition, rabbit antisera
      raised against the P6 peptides reacted equally well with P6 and rP6. Furthermore,
      all human convalescent sera tested exhibited similar anti-P6 and anti-rP6
      antibody titers. However, rP6 was less immunogenic than P6 when administered
      either without adjuvant or in alum and when tested in competitive inhibition
      studies with anti-P6 antibodies, was a less effective inhibitor than native P6,
      suggesting a diminution in some of the antigenic activity of rP6. In spite of
      these differences, rP6 was capable of eliciting a protective antibody response
      against live H. influenzae type b challenge in a modified infant rat model of
      bacteremia. These findings demonstrate that the non-fatty acylated rP6 could
      possibily be substituted for native P6 in a vaccine against H. influenzae.

PMID- 9261945
TI  - OspA lipoprotein of Borrelia burgdorferi is a mucosal immunogen and adjuvant.
AB  - The outer surface protein A (OspA) lipoprotein of Borrelia burgdorferi, like
      cholera toxin and the heat-labile enterotoxin of Escherichia coli, induces pro
      inflammatory cytokines. This suggested that, like those toxins, OspA might be a
      mucosal immunogen and adjuvant. OspA, administered intranasally (i.n.) or
      intragastrically, induced strong serum IgG and salivary gland IgA responses. The
      serum IgG isotypes were indicative of a mixed T helper 1 and T helper 2 response,
      the latter being more pronounced. The N-terminal tripalmitoyl-S-glyceryl-cysteine
      (Pam3Cys) lipid moiety was absolutely required. OspA strongly enhanced the serum
      IgG and salivary gland IgA responses to jack bean urease co-administered by the
      i.n. route. OspA also enhanced the response to tetanus toxoid and induced limited
      protection against challenge. A synthetic lipopeptide also adjuvanted the
      response to urease by the i.n. route, but was ca 500-fold less potent on a molar
      basis than OspA. These results suggest that OspA or other lipoproteins may be
      useful in mucosal vaccines.

PMID- 9261946
TI  - Antibody response to Actinobacillus pleuropneumoniae antigens after vaccination
      of pigs bred for high and low immune response.
AB  - To enhance inherent general resistance to infectious diseases an indirect
      strategy of selective breeding for multiple immune response traits representing
      both antibody and cell-mediated immune response has been pursued over several
      generations in pigs. High and low response lines differ significantly not only in
      response to antigens included in the estimated breeding values upon which the
      selection was based, but also to other antigens. To test whether or not the lines
      also differed in antibody response to vaccination, high and low response pigs
      were given a commercial Actinobacillus pleuropneumoniae vaccine, and their serum
      antibody to three constituent antigens, carbohydrates (CHO) 1 and 5 and
      lipopolysaccharide (LPS) 1 was measured by enzyme immunoassay. The high line had
      significantly (P < or = 0.05) more antibody to all antigens except at day 28 to
      CHO antigen 5. The frequency of non-response to vaccination was also less in the
      high response pigs to CHO antigen 1 (P < or = 0.01) and to the LPS antigen (P <
      or = 0.06) but not to the CHO antigen 5. Based upon these observation it is
      concluded that the high immune response pigs are more responsive to the
      commercial vaccine than are the low response pigs and that the strategy of
      altering population immune response by multi-trait selective breeding may be
      useful in facilitating vaccine-based health management programs for livestock.

PMID- 9261947
TI  - Induction of cross-reactive cytotoxic T-lymphocyte responses specific for HIV-1
      gp120 using saponin adjuvant (QS-21) supplemented subunit vaccine formulations.
AB  - The antigenic variation associated with Human Immunodeficiency Virus type-1 (HIV
      1) envelope proteins could limit their utility in vaccines if the immune
      responses induced are specific for immunodominant variable epitopes. We evaluated
      the ability of experimental subunit vaccines, containing recombinant forms of the
      envelope glycoprotein (rgp120) from two HIV-1 variants, to induce immune
      responses capable of recognizing unrelated HIV-1 variants. A vaccine formulation
      based on HIV-1IIIB/LAI rgp120 and supplemented with saponin adjuvant (QS-21)
      induced neutralizing antibodies specific for the HIV-1IIIB/LAI variant. This
      antibody response was presumably specific for the variable principle neutralizing
      determinant (PND) of the third variable region of gp120, the V-3 region. This
      formulation induced cytotoxic T-lymphocytes (CTL) specific for the dominant V-3
      epitope but also to an additional unidentified epitope outside of this region.
      The CTL specific for this second epitope also recognized gp120 from the HIV-1MN
      and HIV-1RF variants in a "cross-reactive" manner. A second vaccine formulation
      based on HIV-1MN rgp120 and QS-21 adjuvant induced neutralizing antibodies that
      were again variant-specific but also CTL that recognized all three HIV-1 variants
      in a cross-reactive manner. These data demonstrate that CTL capable of
      recognizing different HIV-1 variants, which are presumed to be specific for a
      conserved HIV-1 gp120 epitope, can be induced using subunit vaccines with the
      appropriate adjuvant while variant-specific antibody responses are produced.
      These findings support further evaluation of this vaccine format.

PMID- 9261948
TI  - Influenza vaccination in patients with asthma: effect on peak expiratory flow,
      asthma symptoms and use of medication.
AB  - This pilot study was undertaken to examine whether killed influenza vaccine
      causes exacerbations in asthmatic adults. Thirty-three stable asthmatics recorded
      peak expiratory flow (PEF), asthma symptoms, and use of asthma medication for 2
      weeks, and then received killed influenza vaccine. Thereafter they recorded PEF,
      asthma symptoms and use of medication for a further 2 weeks. Comparison of
      recordings during the 2 weeks before and after vaccination revealed that
      influenza vaccine was not associated with reduction in PEF (P = 0.76), increase
      in asthma symptoms (P = 0.17) or use of asthma medication (P = 0.58). Similar
      results for PEF (P = 0.49), asthma symptoms (P = 0.17), and asthma medication (P
      = 0.16) were obtained when the analysis was restricted to the 2 days before and
      after vaccination.

PMID- 9261949
TI  - A clinical, epidemiological and laboratory study on avoiding the risk of
      transmitting viral hepatitis during vaccinations with the Dermojet protected by
      an anticontaminant disposable device.
AB  - Jet injectors may transmit blood-borne infections, such as hepatitis B virus
      (HBV) and human immunodeficiency virus (HIV). To evaluate the safety of an
      anticontaminant disposable device which protects the jet injector apparatus,
      22,714 healthy subjects were intradermally inoculated (38,162 inoculations) with
      a variety of vaccines. All the subjects were systematically followed-up
      clinically and epidemiologically for 6-18 months after inoculation; blood samples
      from 1619 subjects, before and 60-75 days after inoculation, were examined by
      enzyme-linked immunosorbent assay (ELISA) for HBV, hepatitis C virus (HCV) and
      HIV. Before vaccination 212 (13.09%) subjects were positive: 204 positive for HBV
      markers and eight for the HCV marker. None of the subjects were positive for the
      anti-HIV marker. During the clinico-epidemiological surveillance and the
      laboratory investigations mentioned above no clinical viral hepatitis B or C case
      and no seroconversion to positivity for HBV or HCV markers among the susceptible
      persons in the group were reported. Considering that in similar situations there
      is a theoretical risk of transmission as high as 1 per 388 to 1 per 3367
      injections and that in our case 38,162 inoculations were performed in 22,714
      subjects with the same Dermojet protected by the same type of anticontaminant
      disposable device, no contamination risk being reported, the conclusion can be
      reached that jet injectors can be safely used in the medical practice if they are
      protected by the sterile anticontaminant disposable device.

PMID- 9261950
TI  - Immunoresponse to hepatitis B vaccination and adherence campaign among injecting
      drug users.
AB  - Fifty injecting drug users (IDUs) were recruited to evaluate the efficacy of an
      hepatitis B virus (HBV) vaccination campaign to be carried out in a Public centre
      for Drug Users (PCDU). The vaccination schedule was successfully performed in
      most patients, who showed a great interest in this problem. After three doses of
      vaccine the seroconversion rate, with antibodies against HBV, proved similar to
      the one obtained in another group of healthy men of same age, while the antibody
      titres against HBV were lower after the second and third dose of vaccine.
      Vaccination campaigns for IDUs could lead to successful results in terms of
      compliance and efficacy, but they need to be closely monitored considering the
      IDUs relatively low antibody response.

PMID- 9261951
TI  - Selection of an adjuvant for vaccination with the malaria antigen, MSA-2.
AB  - Various formulations of the Plasmodium falciparum merozoite surface antigen, MSA
      2, were made and tested in animals in order to select one for use in human
      vaccine trials. Recombinant constructs representing both major allelic forms of
      MSA-2 were formulated with a range of adjuvants and used to immunize rabbits,
      mice and sheep. After immunization, antibody responses obtained with the most
      potent adjuvants were at least tenfold greater than responses obtained with the
      least potent adjuvant Alhydrogel, which was used as the reference standard,
      although its lower potency indicated against its further use in clinical trials.
      Based on broadly similar results obtained with the three animal species, several
      adjuvants, including the water-in-oil adjuvant Montanide ISA 720, the oil-in
      water adjuvant SAF-1, and liposomes containing lipid A formulated with Alhydrogel
      were demonstrated to be potent and potentially suitable for the clinical
      evaluation of MSA-2 as a candidate malaria vaccine antigen. Of these, ISA 720 was
      selected for further trial.

PMID- 9261952
TI  - Haemolytic activities of plant saponins and adjuvants. Effect of Periandra
      mediterranea saponin on the humoral response to the FML antigen of Leishmania
      donovani.
AB  - An 87.7% (P < 0.01) and 84% (P < 0.001) of protection against visceral
      leishmaniasis was achieved in CB hamsters and Balb/c mice, respectively, with
      saponin combined to the fucose-mannose ligand of Leishmania donovani (FML).
      However, an undesirable haemolytic effect was described for several saponins.
      Aiming to improve the formulation with FML/saponin, we comparatively analysed the
      haemolytic potential of recently characterized plant saponins and currently used
      adjuvants. The haemolytic activity of steroidic saponins from Agave sisalana;
      Smilax officinalis as well as commercial saponin (Riedel De Haen's), was higher
      than that of triterpenoid ones (Bredemeyera floribunda; Periandra mediterranea)
      and the Freund's complete adjuvant. The concentration resulting in 50% haemolysis
      was 500 micrograms ml-1 for aluminum hydroxide. The low haemolytic effect of P.
      mediterranea saponin was abolished by removal of its glycidic moiety and its
      sapogenin fraction as well as the Freund's Incomplete Adjuvant were non
      haemolytic within this range. Furthermore, the adjuvant effect of three doses of
      P. mediterranea saponin injected with the FML antigen of L. donovani, was assayed
      in mice, either by the intraperitoneal (i.p.) or the subcutaneous (s.c.) route.
      The anti-FML IgG antibody levels increased and detectable levels were observed up
      to 3 months in the s.c. group. The response was expanded in both groups after an
      injection with a fourth vaccine dose. The IgG response showed increased levels of
      IgG2a only in the i.p. group, while IgG2b and IgG1 but not IgG3 antibodies were
      higher than controls in both groups. In conclusion, the results suggest that the
      recently described triterpenoid fractions of P. mediterranea can be safely used
      as adjuvant with low or non-haemolytic effect.

PMID- 9261953
TI  - Kinetics, localization and cytokine profile of T cell responses to immune
      stimulating complexes (iscoms) containing human influenza virus envelope
      glycoproteins.
AB  - Immune stimulating complexes (iscoms) are 40 nm particles combining adjuvant
      active Quillaja saponins and multimeric presentation of antigens. The
      distribution in mice of influenza virus iscoms and the resulting T cell responses
      in the lymph nodes (LN) and spleen were characterized. After a single
      subcutaneous injection, iscoms were delivered to the draining LN where they
      induced a transient population of LN cells which responded with proliferation and
      secretion of interleukin-2 (IL-2), gamma-interferon (IFN-gamma) and interleukin-4
      (IL-4) after restimulation. The response in the spleen developed more slowly,
      sustained for 12 weeks and was characterized by cells producing in particular IL
      2 and IFN-gamma but also IL-4. A booster resulted in a dramatic enhancement of
      the production of IFN-gamma, indicating that iscoms efficiently recruit cells
      with Th1 properties. Comparisons of T cell responses to iscoms and to influenza
      virus antigen in Freund's complete adjuvant demonstrate that these adjuvants
      affect both the localization and cytokine profile of T cell responses.

PMID- 9261954
TI  - Influenza virus neutralizing antibodies and IgG isotype profiles after
      immunization of mice with influenza A subunit vaccine using various adjuvants.
AB  - The influence of various adjuvants on the development of influenza virus
      neutralizing antibodies and distribution of anti-influenza virus IgG isotypes
      after immunization of mice with influenza A (H3N2) subunit vaccine was
      investigated. Serum titres of influenza virus neutralizing antibodies and titres
      of influenza specific IgG isotypes were determined by a neutralization enzyme
      immunoassay (N-EIA) and a cell-associated antigen enzyme immunoassay (CA-EIA),
      respectively. Serum antibody titres as measured by the two tests correlated
      highly (r = 0.82; P < 0.001). N-EIA titres were enhanced by 38- and 34-fold, when
      L180.5/RaLPS and FCA, respectively, were administered with 1 microgram of
      vaccine. The adjuvants Q-VAC, L180.5 [W/O/W], L180.5 alone and Montanide ISA 740
      were only moderately or not effective in enhancing the immune response to the 1
      microgram dose of vaccine. The Q-VAC and L180.5/RaLPS adjuvants favoured IgG2a
      and IgG2b isotype responses to influenza compared to the other adjuvants. We
      suggest that N-EIA and CA-EIA may be valuable tools to monitor the effects of
      adjuvants on the neutralizing antibody and antibody isotype responses after
      influenza vaccination.

PMID- 9261956
TI  - Cell-mediated immune responses to liver membrane protein in canine chronic
      hepatitis.
AB  - Peripheral blood mononuclear cells from dogs with chronic inflammatory liver
      disease and dogs with noninflammatory liver diseases were evaluated for
      proliferative responses to pokeweed mitogen and canine liver membrane protein.
      Dogs with chronic hepatitis were selected based on histopathological evidence of
      periportal lymphocytic infiltrates with or without neutrophilic infiltrates,
      fibrosis and necrosis. Incorporation of tritiated thymidine was assessed 72 hours
      after addition of liver membrane protein or pokeweed mitogen. Peripheral blood
      mononuclear cell proliferation in response to liver membrane protein was
      significantly higher in chronic hepatitis dogs compared to control dogs. Eight of
      12 dogs with chronic hepatitis and 2 of 7 dogs with noninflammatory liver disease
      had proliferative responses to liver membrane protein greater than 2 standard
      deviations above the mean of the control group. These data support the hypothesis
      that immune-mediated processes are involved in canine chronic hepatitis, but did
      not determine whether this is a primary disorder or occurred secondary to liver
      destruction.

PMID- 9261955
TI  - Molecular characteristics of malignant lymphomas in cats naturally infected with
      feline immunodeficiency virus.
AB  - Neoplastic disease, especially malignant lymphomas, are often observed in cats
      infected with feline immunodeficiency virus (FIV). In order to clarify the
      characteristics of lymphoma cells and to investigate the pathogenesis in FIV
      infected cats, we examined the lymphoma tissues developed in five cats naturally
      infected with FIV by Southern blot analyses using feline immunoglobulin (Ig), T
      cell receptors (TCR) and FIV probes. All of the five cases were serologically
      positive for anti-FIV antibody and negative for feline leukemia virus antigen. Of
      these five lymphoma samples, two displayed rearrangement of the Ig heavy chain
      gene and deletion of the Ig light (kappa) chain gene, indicating that the tumor
      cells were committed to B-cell development. One tumor sample was identified as a
      T-cell lymphoma because of the presence of a rearranged TCR beta-chain gene. The
      other two cases were considered to be non-T non-B cell lymphoma because they did
      not show any rearrangement of the Ig and TCR genes. Therefore, no consistent
      tumor type was found in lymphoma cases infected with FIV. Clonal integration of
      FIV provirus was not detected in any of the five lymphoma samples obtained from
      FIV-infected cats using Southern blot analysis, although FIV proviral genome was
      detected in the genomic DNA of all the lymphoma samples by using a polymerase
      chain reaction (PCR). These results indicated that FIV might not play a direct
      role in tumorigenesis of lymphoma in cats.

PMID- 9261957
TI  - Leukocyte mobilization to skin lesions, determination of cell surface receptors
      (CD11b/CD18) and phagocytic capacities of neutrophils in dogs with chronic deep
      pyoderma.
AB  - A suction blister technique was used in eight dogs with chronic deep pyoderma to
      determine chemotaxis in vivo. By flow cytometry the expression of adhesion
      molecules (CD11b/CD18) on exudative and peripheral neutrophils were analyzed in
      11 healthy dogs and six dogs with chronic deep pyoderma. Phagocytosis in vitro
      capacities of exudative and peripheral neutrophils were analyzed in six healthy
      dogs and six dogs with chronic deep pyoderma. Dogs with chronic pyoderma showed
      significantly better chemotaxis in vivo compared with the healthy dogs (P <
      0.05). Expression of adhesion molecules CD11b and CD18, and phagocytosis was
      significantly (P < 0.05) better in the dogs with pyoderma compared with the
      healthy dogs. In both groups exudative cells expressed significantly (P < 0.05)
      more CD11b/CD18 receptors compared with blood neutrophils. We conclude that there
      are no serious functional disturbances detectable in the peripheral neutrophils,
      nor in the exudative neutrophils from dogs with chronic deep pyoderma.

PMID- 9261958
TI  - Detection of equine and bovine T- and B-lymphocytes in formalin-fixed paraffin
      embedded tissues.
AB  - Formalin-fixed paraffin-embedded sections of equine and bovine lymph nodes,
      spleen, thymus, and Peyer's patches were incubated with monoclonal antibodies to
      B-lymphocyte markers BLA.36, B29, and mb-1 and T-lymphocyte markers CD3 and CD5.
      The monoclonal antibody BLA.36 reacted with 80-90% of lymphocytes in the germinal
      centers and mantle zones of follicles in lymph nodes, spleen, and Peyer's
      patches. In addition, 90% of lymphocytes in the marginal zone of the spleen, and
      variable numbers of lymphocytes within lymph node medullary cords were
      immunopositive for BLA.36. Antibodies to B29 and mb-1 produced similar staining
      patterns as BLA.36 with fewer positive cells in the germinal centers and
      medullary cords. BLA.36, B29, and mb-1 reacted with 30-50% of lymphocytes in the
      medulla of the thymus and with 5-10% of lymphocytes in the cortex. CD3 and CD5
      reacted with 90% of lymphocytes in the paracortex and parafollicular zones of
      lymph nodes, spleen, and Peyer's patches; 40-50% of lymphocytes in the medullary
      cords of lymph nodes, and scattered positive cells within follicles. Anti-CD3
      antibody reacted with 95% of lymphocytes in the splenic red pulp, but antibodies
      directed against CD5 reacted only faintly with approximately 5-10% of lymphocytes
      in the red pulp. CD3 and CD5 reacted with 50-60% of cells in the medulla of the
      thymus and with 40-80% of lymphocytes in the thymic cortex. The biochemical
      characterization of the antibodies by Western blotting against lysates of equine
      and bovine peripheral blood mononuclear cells confirmed that antibodies to
      BLA.36, mb-1, B29, CD3, and CD5 detected molecules of the same approximate
      molecular mass as found on lymphoid cells of human beings and rats.

PMID- 9261959
TI  - Cell-mediated cytolysis of equine herpesvirus-infected cells by leukocytes from
      young vaccinated horses.
AB  - The objective of this study was to determine whether the administration of
      modified-live equine herpesvirus (EHV-1) to young horses with residual maternal
      antibodies stimulated EHV-specific cytolytic responses, and whether these
      responses were crossreactive between EHV-1 and EHV-4. Eighteen clinically normal
      Belgian cross-foals were used in the study and were commingled in two adjacent
      pens. Skin biopsies were harvested from 16 foals within 24 h of birth and
      fibroblast cultures were established, expanded and cryopreserved. Beginning at
      approximately 10 weeks of age, 10 randomly chosen foals were inoculated on days
      0, 21, and 43 of the study with a vaccine containing modified-live EHV-1. Blood
      mononuclear leukocytes were obtained on days 0, 32, and 50 for the assessment of
      EHV-specific cytolytic activity using 5 h and 18 h chromium release assays. EHV-1
      specific antibodies were assessed by enzyme-linked immunosorbent assay using
      serum collected on days -21, 0, 32, and 50 of the study. Lymphocyte blastogenic
      tests and bioassays for interferon activity were conducted on day 50. After two
      vaccinations, mononuclear leukocytes from seven of ten vaccinated foals had
      cytolytic activity against autologous EHV-1 cells and leukocytes from six of ten
      lysed EHV-4-infected cells when tested in an 18 h assay. This activity was
      enhanced by exogenous interleukin 2 and was markedly reduced using target cells
      from unrelated horses. Cytotoxicity was not detected in a 5 h assay following in
      vitro stimulation of leukocytes. After three vaccinations, blood leukocytes from
      6/6 vaccinated foals and 0/6 unvaccinated foals had proliferative responses EHV
      1. There were no significant differences in interferon production by leukocytes
      from these foals. Twelve foals tested had low concentrations of (maternal) EHV-1
      specific antibody prior to vaccination. Five of eight foals tested had increases
      in EHV-specific antibodies, while 4/4 commingled unvaccinated foals had a
      decrease or no change in EHV-specific antibodies. These results demonstrate
      cytotoxic cellular immune responses can be induced in young horses with maternal
      antibodies following administration of modified-live vaccine.

PMID- 9261960
TI  - The acute phase serum amyloid A protein (SAA) in the horse: isolation and
      characterization of three isoforms.
AB  - Serum amyloid A (SAA) from acute phase horse serum was isolated using hydrophobic
      interaction chromatography, gel filtration and ion exchange chromatography. Three
      SAA isoforms with different isoelectric points, i.e. SAA pI 8.0, SAA pI 9.0 and
      SAA pI 9.7, were identified by two-dimensional electrophoresis and further
      characterized with amino acid sequence analysis. These isoforms were found in
      similar concentrations in all animals investigated, with SAA pI 9.7 constituting
      about half of the total SAA content. Partial amino acid sequence analysis
      verified the previously published heterogeneous SAA sequence. SAA pI 8.0 was
      found to have isoleucine in Position 16, glutamine in Position 44 and glycine in
      Position 59. SAA pI 9.0 had leucine, glutamine and alanine in the corresponding
      positions. In SAA pI 9.7 leucine, lysine and alanine were detected. The three
      isoforms characterized in this study are all acute phase SAAs. SAA pI 9.0 and 9.7
      correspond to amyloid A protein variants previously isolated from amyloid
      deposits of equine liver, while there are no reports on an amyloid A variant
      corresponding to SAA pI 8.0.

PMID- 9261961
TI  - The immune response of foetal calves.
AB  - The immunological response of foetal calves to tetanus toxoid was investigated.
      Emphasis was placed on foetal immunocompetence and how this related to responses
      seen in adult cattle. The establishment of indwelling cannulas in the efferent
      prescapular lymphatic ducts and superficial veins of foetal calves allowed
      continual monitoring of cellular and humoral changes in efferent lymph and
      peripheral blood. Foetal calves from 195 to 253 days gestational age had the
      capacity to mount cell-mediated and humoral immune responses of similar character
      and magnitude as adult cattle to tetanus toxoid. Intravenous and subcutaneous
      routes of challenge with tetanus toxoid resulted in specific antibody production
      which peaked 26 to 31 days after vaccination. Significant tetanus toxoid
      stimulated lymphocyte proliferation was present 4 to 6 weeks after vaccination
      with tetanus toxoid in both a foetus and an adult. After antigenic challenge
      lymphocytes remained the predominant cell type in efferent prescapular lymph of
      foetuses and cows while at the same time a marked shift to the left,
      characterised by band neutrophils and neutrophilic metamyelocytes occurred in
      peripheral blood. Lymph flow rate increased and cell concentration decreased
      after antigenic challenge.

PMID- 9261962
TI  - Modulation of endotoxin-induced inflammation in the bovine teat using
      antagonists/inhibitors to leukotrienes, platelet activating factor and
      interleukin 1 beta.
AB  - A leukotriene biosynthesis inhibitor (MK886), a platelet-activating factor (PAF)
      receptor antagonist (WEB 2086), a recombinant human interleukin-1 receptor
      antagonist (IL-1ra) and a polyclonal antibody to recombinant bovine IL-1 beta
      (anti-rBoIL-1 beta) was used to investigate the involvement of leukotrienes, PAF
      and IL-1 beta during endotoxin-induced inflammation in the bovine teat cistern.
      Endotoxin alone was infused into one teat cistern and endotoxin in combination
      with an inhibitor/antagonist was infused into another teat cistern of the same
      animal. Teat cistern samples were taken before infusion and at 3.5 and 7 h after
      infusion, and the numbers of neutrophils were counted. Saline infusion was used
      as control. The inhibitors/antagonists were also tested in combination with
      leukotriene B4 (LTB4), PAF and rBoIL-1 beta, respectively. MK886 or WEB 2086
      significantly reduced the accumulation of neutrophils mainly between 3.5 and 7 h
      after infusion, indicating roles for leukotrienes, probably LTB4, and PAF in
      neutrophil accumulation during endotoxin-induced inflammation. As WEB 2086 also
      reduced cell accumulation between 0 and 3.5 h, PAF was implicated also in the
      early influx of neutrophils. WEB 2086 almost completely inhibited PAF-induced
      cell accumulation between 0 and 3.5 h. LTB4 did not induce significant cell
      accumulation in the teat cistern. IL-1ra did not affect endotoxin-induced
      neutrophil accumulation whereas anti-rBoIL-1 beta reduced total cell accumulation
      and, to some degree, accumulation between 0 and 3.5 h after infusion. Infusion of
      IL-1ra significantly inhibited cell accumulation induced by rBoIL-1 beta. Anti
      rBoIL-1 beta also significantly reduced neutrophil accumulation induced by rBoIL
      1 beta, but to a lesser degree. The results suggest roles for leukotrienes, most
      likely LTB4, and PAF, and to a lesser extent IL-1 beta, during endotoxin-induced
      neutrophil migration into the bovine teat cistern. The potential of the
      inhibitors/antagonists as therapeutic agents for bovine mastitis should be
      investigated.

PMID- 9261963
TI  - Quantification of total sheep IgE concentration using anti-ovine IgE monoclonal
      antibodies in an enzyme immunoassay.
AB  - Monoclonal antibodies (mAbs) which recognize separate epitopes on ovine
      immunoglobulin E (IgE) have been used to develop a non-competitive antibody
      sandwich enzyme immunoassay (EIA) for quantitating ovine IgE. Purified anti-IgE
      mAb (YD3) coated onto polystyrene microtitre plates was used to capture IgE in
      serum samples. Biotinylated anti-IgE mAb (XB6) followed by streptavidin
      conjugated with horseradish peroxidase were used to detect captured IgE.
      Tetramethylbenzidine and H2O2 were used as enzyme substrate. A reference serum
      was prepared by pooling sheep sera containing elevated IgE levels. This reference
      serum was assigned a value of 100 units ml-1 and used to prepare standard curves
      for the EIA. The linear region of log-log transformed standard curve data covered
      a range of 0.05-0.8 units ml-1. The equation of a linear regression line fitted
      to this curve was used to determine sample concentrations. Using purified IgE, 1
      unit of reference serum was equivalent to 0.86 micrograms ml-1 IgE. Maximum intra
      and inter-assay coefficients of variation for the EIA were 4.6% and 9.7%,
      respectively. Subjecting serum samples to 15 freeze/thaw cycles, storage at room
      temperature for 16 days or incubation at 37 degrees C for 8 h resulted in minimal
      loss of IgE detection. Incubation of serum at 56 degrees C resulted in rapid
      reduction in detection of IgE by the EIA. The assay was used to determine IgE
      levels in adult sheep monospecifically infected with weekly doses of the nematode
      Trichostrongylus axei. Serum IgE levels increased from 9 to 16 days following
      first infection and reached maximum levels by days 35-58. Serum IgE responses
      closely followed IgE positive cell responses in the abomasal mucosa.

PMID- 9261965
TI  - Heterogeneity of porcine alveolar macrophages in experimental pneumonia.
AB  - The aim of the study was the morphological and the phenotypic characterization of
      the porcine non-lymphocytic bronchoalveolar lavage (BAL) cell population of
      unaffected- and intrabronchial with Pasteurella multocida- (P.m.) infected swine
      using flow cytometry. Three non-lymphocytic cell populations of the porcine
      bronchoalveolar lavage could be differentiated: (1) large, high autofluorescent
      cells, (LHC); (2) small, high autofluorescent cells, (SHC); (3) small, low
      autofluorescent cells, (SLC). In comparison with the control animals, the
      percentage of the LHC and SHC within the whole non-lymphocytic cell population
      was decreased, whereas the SLC was significantly enhanced after infection. In
      order to investigate the phenotype of these cell populations, monoclonal
      antibodies against porcine antigens (SWC1, SWC3a, MHC class II, 2G6 (against
      macrophages)) were used. The results showed that the cells of the SLC seem to
      belong to the granulocytes, whereas the LHC and the SHC are lung macrophages.
      After the infection of the animals the percentage of the SWC1 positive cells of
      LHC and SHC were significantly increased, indicating an entrance of more immature
      macrophages. The percentage of the MHC class II antibody binding cells of all
      three non-lymphocytic populations was-decreased after infection, indicating a
      restricted MHC class II dependent antigen recognition in P.m. pneumonia.

PMID- 9261964
TI  - Analysis of ovine IL-1 beta production in vivo and in vitro by enzyme immunoassay
      and immunohistochemistry.
AB  - A monoclonal antibody (mAb) specific for ovine IL-1 beta was produced and, in
      conjunction with a polyclonal rabbit antiserum, used to develop a sensitive
      enzyme immunoassay (EIA) for ovine interleukin 1 beta (IL-1 beta). The mAb
      neutralised the activity of recombinant ovine IL-1 beta (rOvIL-1 beta) and native
      OvIL-1 in an ovine thymocyte proliferation assay. However, it did not neutralise
      the biological activity of rOvIL-1 beta in the murine NOB1/CTLL assay. The mAb
      did not react with rOvIL-1 alpha, IL-2, IL-4, IL-8, tumor necrosis factor-alpha,
      gamma-interferon or recombinant human IL-1 beta in indirect EIA.
      Immunohistological staining of activated alveolar macrophages and frozen lymph
      node sections sections demonstrated that the mAb detected IL-1 beta secreted by
      ovine macrophages (CD11c-positive). The EIA was highly sensitive, detecting less
      than 50 pg ml-1 of rOvIL-1 beta and low levels of native IL-1 beta in
      supernatants from lipopolysaccharide-stimulated macrophages. The EIA did not
      detect heat-inactivated IL-1 beta.

PMID- 9261966
TI  - Chicken-embryo fibroblasts produce two types of interferon upon stimulation with
      Newcastle disease virus.
AB  - Controversy has long surrounded the question of whether chickens, like mammals,
      can produce two types of interferon (IFN). Recently, type-I and type-II chicken
      IFNs have been cloned. Our study focuses on the further characterization of
      native fibroblast and spleen IFNs and shows that chicken embryo fibroblasts
      (CEFs) produce a mixture of type-I and type-II IFNs. IFN was purified by three
      different methods, controlled pore-glass chromatography, ion-exchange
      chromatography and preparative SDS-PAGE. Three protein bands showing IFN-like
      anti-viral activity, from CEFs which had been virus-stimulated for IFN
      production, were detected at 25, 27 and 29 kDa. Polyclonal antibodies produced
      against these bands showed partial cross-reaction with purified media from
      mitogen-stimulated spleen cells in ELISA, western blot analysis and anti-viral
      activity neutralization assay. Differences between purified conditioned media
      from CEF and spleen were found with respect to the stimulation of macrophages for
      nitric oxide production, pH stability and signal transduction pathways; only CEF
      IFN activated the IFN-stimulated gene factor-3 complex, whereas both CEF and
      spleen IFNs activated the IFN regulatory factor-1 gene. These findings concur
      with the differences that are known to exist between mammalian type-I and type-II
      IFNs. Attempts at sequencing the 25 and 27 kDa proteins by Edman degradation
      yielded evidence of N-terminal blockage.

PMID- 9261967
TI  - Monoclonal and polyclonal antibodies to chicken immunoglobulin isotypes
      specifically detect turkey immunoglobulin isotypes.
AB  - Turkey immunoglobulin (Ig) isotypes IgG and IgM were isolated from blood and IgA
      was isolated from bile. Isolation was accomplished by gel filtration of the
      ammonium sulphate cut on Sephacryl S-200. Using immunoelectrophoresis and
      indirect ELISA, the cross-reactivity between antibodies, of monoclonal and
      polyclonal origin, specific for the Ig isotypes of chicken, and the purified
      turkey Ig isotypes was evaluated. Commercially available polyclonal antibodies,
      anti-chicken/IgA (alpha-chain specific, affinity purified), anti-chicken/IgG (Fc
      fragment specific) and anti-chicken/IgM (mu-chain specific) showed an
      interspecies cross-reactivity with the corresponding turkey Ig isotypes. The
      monoclonal antibody (MAb) AV-G3 specifically detected turkey IgG, whereas MAb M1
      reacted exclusively with turkey IgM. This panel of anti-immunoglobulins
      represents a useful tool for examining the humoral immune responses of turkeys.

PMID- 9261968
TI  - Detection of homocytotropic antibody in lambs infested with the louse, Bovicola
      ovis, using a basophil histamine-release assay.
AB  - The utility of a basophil histamine-release assay using washed whole blood cells
      was examined in lambs and was used to determine if homocytotropic antibody with
      specificity for Bovicola ovis was produced in response to infestation with the
      louse. Maximal histamine release in the assay in response to Concanavalin A, anti
      ovine IgE monoclonal antibody and, in sensitized lambs, to B. ovis antigen ranged
      from 18 to 48%. Histamine release from blood cells in response to B. ovis antigen
      was significantly higher in louse-infested lambs than in louse-naive lambs and
      was significantly correlated with louse and cockle scores. Passive cutaneous
      anaphylaxis (PCA) tests were negative with sera obtained from the lambs at the
      same time as blood for the basophil histamine-release assay. Serum histamine
      levels also were significantly higher in the louse-infested lambs than in louse
      naive lambs and were significantly correlated with louse and cockle scores. The
      present results support a role for B. ovis-specific homocytotropic antibody in
      the development of cockle and indicate that the basophil histamine-release assay
      is more sensitive than the PCA test.

PMID- 9261969
TI  - Myeloperoxidase activity in chicken heterophils and adherent cells.
AB  - Chicken heterophils are known to lack myeloperoxidase (MPO) activity. In this
      paper, evidence is presented to show that chicken heterophils and adherent cells
      contain a DNA sequence that is homologous to segment 10 of the human MPO gene;
      histochemical staining and microplate assay also show that heterophils and
      adherent cells contain MPO activity.

PMID- 9261970
TI  - Separation of carp (Cyprinus carpio L.) thrombocytes by using a monoclonal
      antibody, and their aggregation by collagen.
AB  - A monoclonal antibody against carp peripheral blood leucocytes was produced, and
      its reactivity analysed by flow cytometry and electron microscopy. The antibody
      reacted positively with 10-35% of the cells in a fraction of lymphocytes and
      thrombocytes that was separated by flow cytometry. Electron microscopy using
      immunogold labelling showed that this antibody reacted strongly with
      thrombocytes, but not with other leucocytes. By using a magnetic separator,
      leucocytes that were positive and negative for this antibody were separated. The
      positive cells were uniform, spindle-type cells that aggregated in the presence
      of collagen, while the negative cells did not aggregate. Light and electron
      microscopy showed that many positive cells changed to a spherical form after the
      addition of collagen and then 40-60% of these cells aggregated.

PMID- 9261971
TI  - Veterinary parasitology in South Africa: some highlights of the past 100 years.
AB  - The reasons for the wide range of parasites occurring in South Africa are
      mentioned. An account is given of the establishment of veterinary research and
      training in South Africa. Some major breakthroughs and advances in the study or
      the control of ecto- and endoparasites as well as protozoal diseases are listed.

PMID- 9261972
TI  - Sustainable tick and tickborne disease control in livestock improvement in
      developing countries.
AB  - Tick and tickborne disease (TTBD) control is a major component of animal health
      programmes protecting livestock, thereby enhancing global food security. The
      present methods for TTBD control are reviewed and an integrated use of the tools
      is recommended with a broader view of how to link TTBD control to the control of
      other parasitic diseases. The work of FAO in this field is presented and it is
      advocated that, although there are still areas that need further investigation, a
      stage has been reached where robust integrated TTBD control schemes, based on
      ecological and epidemiological knowledge of ticks and their associated diseases,
      can be promoted and implemented. Major challenges are the implementation of these
      policies in the field through the continuation of the present on-going programme
      in Africa and support to Latin America and Asia. The importance of involving all
      parties, governments, international and private organisations and the
      agrochemical industry in developing sustainable, cost-efficient control
      programmes is stressed and a global strategy is proposed. The main thrust should
      now be to convince policy makers on the adoption of the strategies and
      veterinarians and farmers on their implementation.

PMID- 9261973
TI  - Alternatives to animal experimentation in parasitology.
AB  - In parasitology, several measures can contribute to the aims of 3R (Reduction,
      Refinement and Replacement of animal experimentation). These include legal
      regulations, international guidelines for evaluating antiparasitic drugs, the
      refinement of animal models for parasitic infections, cryopreservation and
      cultivation of parasites in vitro or in chicken eggs, the maintenance of
      arthropods by artificial feeding, and the use of immunological and molecular in
      vitro techniques (e.g. the production of recombinant antigens for vaccines).
      Considerable progress has been achieved in the development of alternative
      techniques but both their standardisation and validation are not far advanced. A
      wider acceptance and use of alternative methods will only be achieved if research
      can offer economic alternatives that are as effective and reliable as animal
      experiments. Great efforts are needed for further progress.

PMID- 9261974
TI  - New approaches to the integrated control of trypanosomosis.
AB  - Trypanosomosis is one of the most devastating diseases of animals and man in Sub
      Saharan Africa. Over the past century numerous methods of control have been
      developed yet the disease has proved very difficult to eradicate. Current methods
      to control the parasite, in the absence of a vaccine, have to rely on the use of
      trypanocidal drugs and trypanotolerant breeds of livestock. Vector control
      previously depended on ground and aerial spraying of insecticide but now depends
      on the use of traps, targets and bait technology. The application of insecticides
      to cattle is currently of particular interest. Unfortunately all of the current
      methods of control have disadvantages and none has proved to be sustainable.
      There is growing interest in integrated control which can be at three levels;
      integration with rural development, integration with other disease control
      measures and integration of various tsetse and trypanosomosis control measures.
      It is anticipated that distinct benefits can be achieved by an integrated
      approach which will improve the effectiveness of control and enhance the
      prospects of sustainability.

PMID- 9261975
TI  - Wildlife parasites: lessons for parasite control in livestock.
AB  - For sustainable livestock production it is suggested that the parasitologist take
      a leaf out of Nature's book in the search for solutions to the mounting problems
      concerning parasite control. While the farmer has come to regard all parasites
      affecting livestock as entirely without benefit, indigenous parasites and
      diseases are normal and play an essential role as interacting components of a
      natural environment in an ecosystem such as the 19,000 km2-sized Kruger National
      Park, Republic of South Africa. The parasites help to select their hosts for
      fitness and are assisted by predators and intra-species territorial aggression
      which continually eliminate the weak individuals from the system. It is essential
      to guard against the introduction of foreign parasites or infectious agents which
      have no real ecological niche or role in an established ecosystem, however, as
      they cause untoward interactions, sometimes of a violent nature. The policy must
      be to block off or, failing that, to control or eliminate these foreign parasites
      and diseases as far as possible. Often, when Man intervenes in an ecosystem, it
      leads to stress, overcrowding and stagnation and predisposes to disease and
      death. Intensification of the system, as in farming units, denies Nature the
      chance to manage on its own, because of clashing interests with Man. Frank
      parasitism and disease should almost invariably be seen as indicators of an
      imbalance in the ecosystem and should be rectified. Chemicals and vaccines should
      be used to produce sufficient food for all, but without exploiting Nature, or
      else Nature will be unable to continue catering for Man's needs.

PMID- 9261977
TI  - Sense or nonsense? Traditional methods of animal parasitic disease control.
AB  - In recent years, there has been a resurgence of interest in traditional health
      care practices in the western as well as in the developing world. In animal
      health, this has led to further interest in ethnoveterinary research and
      development, a relatively new field of study that covers traditional practices,
      ethnobotany and application of animal care practices embedded in local tradition.
      This development has practical applications for animal parasite control, whether
      related to epidemiology, diagnostics and therapy, or to comprehensive disease
      control methods leading to integrated pest/disease management. Examples are
      provided of traditional practices in diagnostics, herd-, grazing- and pasture
      management as well as of manipulation and treatment. Many of these applications
      indicate a basic understanding of disease, especially epidemiology, by farmers
      and herders, although not always explained, or explainable, in rational western
      ways. Although abuse and quackery exist, the application of traditional practices
      seems to make sense in areas without adequate veterinary services. Moreover,
      acknowledgement of the value of traditional knowledge empowers local
      herders/farmers to try to solve their herds' disease problems in a cost-effective
      way. Traditional practices often make sense, albeit with some regulation to
      ascertain safety and to prevent abuse.

PMID- 9261976
TI  - Application of molecular biology in veterinary parasitology.
AB  - The number of applications of molecular biology in veterinary parasitology is
      increasing rapidly. The techniques used with eukaryotic cells are generally
      applicable to the study of parasites and their hosts. The polymerase chain
      reaction is particularly important for identification and diagnosis of parasites,
      as well as for many other applications. With species and type specific probes or
      primers, sensitivities and specificities unheard of with conventional techniques
      can be achieved. The accumulation of more information on the DNA sequences of
      parasites will reveal many more unique sequences which can be used for
      identification, diagnosis, molecular epidemiology, vaccine development and for
      studying the evolutionary biology and the physiology of parasites and the host
      parasite relationship. Similarly, the completion of genome projects on host
      organisms will greatly assist efforts to select for hosts that are genetically
      resistant to parasite infection. The study of the molecular biology of
      antiparasitic drug receptors, potential targets for chemotherapy, and the
      molecular genetics of drug resistance will allow molecular screens to be used
      with combinatorial chemistry in the search for new antiparasitic drugs,
      improvements to existing chemotherapeutic families and better diagnosis and
      monitoring of drug resistance. While there is a proliferation of molecular
      biology techniques, the availability of simple kits and of automated techniques
      and services for sequencing, library construction and oligonucleotide synthesis
      and other procedures is making it easier for non-specialists to apply many of the
      common techniques of molecular biology. Molecular biology and the benefits from
      its application are relevant for veterinary parasitologists in developing
      countries as well as developed countries and we should introduce aspects of
      molecular biology to the teaching and training of veterinary parasitologists.

PMID- 9261978
TI  - Sustainable helminth control of ruminants in developing countries.
AB  - Widespread anthelmintic resistance, at least amongst the important nematode
      parasites of small ruminants, threatens the sustainability of these livestock
      industries throughout both the developed and developing world. The exacerbation
      of this problem over the last decade or so, has provided the impetus for research
      into non-chemotherapeutic parasite control alternatives, such as host genetic
      resistance, grazing management, worm vaccines and biological control. Although
      some of these options provide practical benefits if currently adopted, or
      exciting prospects for the future, collectively they are unlikely to dispense
      with the need for the timely intervention of effective anthelmintic treatment.
      The issue of sustainability of helminth control practices therefore rests with
      the preservation of anthelmintic effectiveness through the implementation of
      principles of integrated pest management. Herein lies the difficulty-putting the
      principles into practice. Much of the research into sustainable nematode parasite
      control of ruminants has been done in the developed rather than the developing
      world, and the efforts to transfer this information to livestock owners has also
      been commensurately greater in the former. However the need for research and
      technology transfer is much more urgent in the developing world because of the
      lack of scientific and financial resources, the greater dependence on livestock
      industries and the much greater severity of the problem of anthelmintic
      resistance. This will require a major philosophical change in the affluent
      western world to the funding of national and international aid organisations who
      are largely responsible for these activities.

PMID- 9261979
TI  - Novel vaccines for ectoparasites.
AB  - Novel vaccines against ectoparasites have the potential to be cost-effective new
      technology for pest control that avoids some of the real and perceived problems
      with insecticide and acaricide usage. Nevertheless, their development is in its
      infancy. A vaccine against the cattle tick Boophilus microplus, the world's first
      vaccine against an ectoparasite, is in field use in Australia. Considerable
      effort had gone into the development of a vaccine against the sheep blowfly
      Lucilia cuprina, while other vaccines are at an earlier stage of development. The
      identification of critical antigens and their production as effective recombinant
      proteins remains the greatest hurdle. Characteristics of the few known antigens
      and the mode of action of the protective immune response are discussed.
      Development of further vaccines will depend on recognition of likely antigenic
      targets. The efficacy of such vaccines will depend on the characteristics of the
      target species, in particular its digestive biology and the way in which the
      novel vaccine impacts on the parasite population.

PMID- 9261980
TI  - Life on biomembranes viewed with the atomic force microscope.
AB  - Since its invention in 1986, the atomic force microscope (AFM) has become one of
      the most widely used near-field microscopes. Surfaces of hard samples are imaged
      almost routinely with atomic resolution. Soft biological surfaces, however, are
      still challenging. In this brief review, the AFM technique is introduced to the
      experimental biologist. We discuss recent data on imaging molecular structures of
      biomembranes, and give detailed information on the application of the AFM with
      three representative examples. One is imaging plasma membrane turnover of
      transformed renal epithelial cells during migration in vivo, another is
      visualizing a cloned and isolated potassium channel usually located in kidney,
      and a third is imaging macromolecular pore complexes of the nuclear envelope of
      aldosterone-sensitive kidney cells and of Xenopus laevis oocytes. The review ends
      with the conclusion that nuclear pores can serve as birthday candles on a
      Guglhupf.

PMID- 9261981
TI  - Tracing the Na/K-ATPase with rubidium.
AB  - Rubidium (Rb) was used as a marker ion for K to assess Na/K(Rb)-ATPase activity
      in single renal tubule cells. Initial Rb uptake rates were measured by electron
      microprobe analysis in individual tubule cells of the rat kidney during acute
      stimulation or during inhibition of transepithelial Na absorption. Under these
      conditions, Rb uptake closely correlates with intracellular Na concentrations,
      indicating that the intracellular Na concentration is a major determinant in the
      precise adjustment of basolateral, Na/K(Rb)-ATPase-dependent Na extrusion to Na
      entry across the apical cell membrane. Chronically increased distal Na delivery
      induced by loop diuretics triggers adaptive processes which allow increased
      transcellular Na movement at normal or near-normal intracellular Na
      concentrations.

PMID- 9261982
TI  - Mechanisms and regulation of H+ transport in distal tubule epithelial cells.
AB  - The mechanism of acidification in the cortical distal tubule of mammalian kidney
      was analysed by "in vivo" microperfusion and using MDCK cells in culture, by
      electrophysiological and by cell pH microfluorescence techniques. An electrogenic
      effect of the vacuolar H(+)-ATPase, which has been localized to the intercalated
      cells of the cortical distal tubule (connecting segment and initial collecting
      duct) was only observed after blocking Cl- channels by NPPB. In MDCK cells, the
      recovery of cell pH after an acid pulse in Na(+)-free medium was also depressed
      by NPPB, indicating that Cl- ions have an important role in the function of H+
      ATPase. The regulation by hormonal agents of distal H+ transport due to Na+/H+
      exchange and to vacuolar H+ ATPase, was also studied by microperfusion and cell
      pH techniques. Angiotensin and vasopressin at picomolar concentrations stimulated
      both transport mechanisms in late distal tubule, and only Na+/H+ exchange in the
      early segment. In MDCK cells, cell pH recovery in the presence of Na+ was
      stimulated by picomolar concentrations of angiotensin and vasopressin, and
      inhibited by micromolar levels, both effects being reverted by micromolar ANP.
      Studies with specific antagonists suggest that the luminal effect of angiotensin
      is mediated by AT1 receptors, and of vasopressin by V1 receptors. There is
      evidence that cell Ca2+ may have an important regulatory role in the action of
      these hormones.

PMID- 9261983
TI  - Ion exchangers mediating NaCl transport in the proximal tubule.
AB  - We have studied the mechanisms of NaCl transport in the mammalian proximal
      tubule. We identified Cl(-)-formate and Cl(-)-oxalate exchangers as possible
      mechanism's of uphill Cl- entry across the apical membrane of proximal tubule
      cells. For steady state Cl- absorption to occur by these mechanisms, formate and
      oxalate must recycle from lumen to cell. Recycling of formate from lumen to cell
      may occur by H(+)-coupled formate transport and nonionic diffusion of formic acid
      in parallel with Na(+)-H+ exchange. Oxalate recycling from lumen to cell may take
      place by oxalate-sulfate exchange in parallel with Na(+)-sulfate cotransport. Cl-
      exit across the basolateral membrane is most likely mediated by Cl- channels. To
      identify the Na(+)-H+ exchanger (NHE) isoform(s) expressed on the brush border
      membrane of proximal tubule cells, we developed isoform-specific monoclonal and
      polyclonal antibodies. We found that NHE1 is present on the basolateral membrane
      of all nephron segments, whereas NHE3 is present on the apical membrane of cells
      in the proximal tubule and the thin and thick limbs of the loop of Henle. NHE3 is
      also present in a population of subapical intracellular vesicles, suggesting
      possible regulation by membrane trafficking. The inhibitor sensitivity of Na(+)
      H+ exchange in renal brush border vesicles indicates that it is mediated by NHE3
      under baseline conditions and during up-regulation by metabolic acidosis.
      Increased apical membrane Na(+)-H+ exchange activity in response to metabolic
      acidosis and during renal maturation is associated with increased NHE3 protein
      expression. Finally, we found that the organic anion-dependent absorption of Cl-
      is markedly down-regulated in metabolic acidosis in parallel with the up
      regulation of brush border membrane Na(+)-H+ exchange. Thus, differential
      regulation of apical membrane ion exchangers may provide a mechanism to regulate
      the relative rates of NaHCO3 and NaCl reabsorption.

PMID- 9261984
TI  - Membrane traffic and control of proximal tubular sodium phosphate (Na/Pi)
      cotransport.
AB  - Phosphate (P(i)) is freely filtered at the glomerular capillaries and largely
      reabsorbed in the proximal tubule by a Na-dependent, secondary active transport
      mechanism. Two different brush border membrane Na/P(i)-cotransporters have
      recently been "cloned" (type I and type II). Only the type II transporter
      undergoes physiological regulation (e.g., diet, acid/base, parathyroid hormone);
      it is also involved in pathophysiological alterations of renal Pi-handling (e.g.,
      X-linked hypophosphatemia). In recent experiments on rats and on tissue culture
      cells (Opossum kidney cells, OK cells) id was documented that manoeuvres leading
      to increased uptake involve membrane insertion (fast changes) and new synthesis
      of type II transporters (slow changes), whereas decreased Na/Pi-cotransport
      activity is associated with their specific membrane retrieval (fast changes) and
      lysosomal degradation (slow changes).

PMID- 9261985
TI  - The electrogenic Na/HCO3 cotransporter.
AB  - The electrogenic Na/HCO3 cotransporter (symporter) is the major HCO3- transporter
      of the renal proximal tubule (PiT), located at the basolateral membrane (BLM),
      and also plays a noteworthy role in Na+ reabsorption. HCO3 transporters are
      important for regulation of intracellular pH (pHi) in most cells and also thereby
      regulate blood pH. This electrogenic Na/HCO3 cotransporter was first discovered
      using perfused Ambystoma tigrinum (salamander) renal, proximal tubules. This
      novel cotransporter mediates the movement of one Na+ ion with several HCO3- ions,
      making it electrogenic, is blocked by stilbene compounds, but does not depend on
      intra- or extracellular Cl-. This and similar cotransporters have been found in a
      number of tissues and cell types. Recently, we used Xenopus-laevis oocytes to
      expression clone the salamander renal electrogenic Na Bicarbonate Cotransporter
      (NBC). Using microelectrodes to monitor membrane potential (Vm) and intracellular
      pH (pHi), we followed oocyte expression after injecting poly (A)+, fractioned
      poly (A)+, or cRNA. All experimental solutions contained 100 microM ouabain to
      block the Na+/K+ pump. Our expression assay was to apply 1.5% CO2/10 mM HCO3- (pH
      7.5), allow pHi to stabilize from the CO2-induced acidification, and then remove
      bath Na+. Removing bath Na+ from native oocytes and water-injected controls,
      hyperpolarized the oocytes by approximately 5 mV and had no effect on pHi.
      However, for oocytes injected with poly (A)+ RNA, removing Na+ transiently
      depolarized the cell by approximately 10 mV and caused pHi to decrease; both
      effects were blocked by 4,4'-diisothiocyano-2,2'-stilbenedisulfonate (DIDS) and
      required HCO3-. Electrophoretic fractionation of the poly (A)+ RNA, enriched the
      expression signal. From the optimal expression-fraction, we constructed a size
      selected cDNA library in pSPORT1. Screening our Ambystoma library yielded a
      single clone (aNBC). We could detect expression 3 days after injection of NBC
      cRNA. In aNBC-expressing oocytes, adding CO2/HCO3-elicited a large (> 50mV) and
      rapid hyperpolarization, followed by a partial relaxation as pHi stabilized. Na+
      removal in CO2/HCO3-depolarized the cell by > 40mV and decreased pHi, aNBC
      encodes a protein of 1035 amino acids with several putative membrane-spanning
      domains, and has a low level of amino-acid homology (approximately 30% to the AE
      family of Cl-HCO3 exchangers. aNBC is the first member of a new family of Na(+)
      linked HCO3- transporters and, together with the AE family, defines a new
      superfamily of HCO3- transporters. Using aNBC to screen a rat-kidney cDNA
      library, we identified a full-length cDNA clone (rNBC), rNBC encodes a protein of
      1035 amino acids, is 86% identical to aNBC, and can be functionally expressed in
      oocytes.

PMID- 9261986
TI  - Cystic fibrosis transmembrane conductance regulator (CFTR) and renal function.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel is
      expressed in all nephron segments. Although mutations in CFTR are not associated
      with major changes in renal function, drug excretion by the kidneys is altered in
      cystic fibrosis (CF) as is the ability of the kidneys to concentrate and dilute
      the urine and excrete a salt load. It is not clear if these changes in renal
      function are secondary to decreased extracellular fluid volume caused by
      excessive losses of NaCl in sweat and feces or if they are related to primary
      defects in renal function caused by mutations in CFTR. Considerable evidence
      supports a role for CFTR in mediating Cl- secretion by the distal tubule,
      principal cells in the cortical collecting duct (CCD) and the inner medullary
      collecting duct (IMCD). In addition, CFTR is responsible for Cl- secretion into
      the lumen of cysts in polycystic kidneys and, therefore, contributes to cyst
      enlargement. Under some conditions--when Na+ absorption across the apical
      membrane of principal cells in the CCD is stimulated and the apical membrane
      potential is depolarized--the electrochemical gradient for Cl- will support Cl-
      absorption via CFTR Cl- channels. In addition to its function as a 3',5'-cAMP
      activated Cl- channel, CFTR may play a role in intracellular vesicle
      acidification, protein processing, protein trafficking, secretion of ATP and the
      regulation of the epithelial Na channel (ENaC) and the secretory K+ channel
      (ROMK2) which mediate Na+ and K+ transport, respectively, across the CCD. Thus,
      CFTR may regulate Na+ and K+ excretion by the kidneys. The most common mutation
      in CFTR is delta F508, a mutation which causes improper folding of CFTR such that
      it is retained within the endoplasmic reticulum where it is degraded. Thus, in
      the majority of cases, CF is a trafficking disease. However, nothing is known
      about the intracellular trafficking of CFTR in the kidney. In preliminary studies
      we have developed a living cell model to study the intracellular trafficking of
      CFTR and delta F508-CFTR in renal epithelial cells in real time. Our ultimate
      goal is to elucidate the intracellular trafficking of CFTR and to identify
      therapeutic approaches to restore normal function to renal cells in CF and to
      block CFTR-mediated Cl- secretion in cysts in polycystic kidneys.

PMID- 9261987
TI  - Medullary thick limb basolateral Cl- channels.
AB  - Chloride transport by the medullary thick ascending limb is a major determinant
      of urinary concentrating and diluting power and also of tubuloglomerular
      feedback. In this review, we discuss the electrophysiologic, regulatory, and
      molecular features of a Cl- channel present in basolateral membranes from the
      medullary thick ascending limb. Functional and immunohistochemical data support
      the view that rbCIC-Ka, a CIC Cl- channel cloned from rabbit kidney medulla, may
      be the Cl- channel which mediates basolateral Cl- efflux.

PMID- 9261988
TI  - Structure and function of the low conductance KATP channel, ROMK.
AB  - The renal ATP-sensitive low-conductance K+ channel (KATP) plays an important role
      in K+ recycling in the thick ascending limb and in K+ secretion in the collecting
      duct. The low-conductance KATP is stimulated by cAMP-dependent protein kinase A
      and inhibited by protein kinase C, arachidonic acid, acidic pH and sulfonylurea
      agents. We reviewed the progress concerning the properties of the recently cloned
      inward-rectifying K+ channel (ROMK or KirI) and compared their regulatory
      mechanisms with the native low-conductance KATP. The results are important to
      gain insight into molecular mechanisms by which ROMK channels are regulated.

PMID- 9261989
TI  - Transport of water in proximal kidney tubules from whole tubules to single
      channels: length and section of the selectivity filter of aquaporin-1.
AB  - Proximal straight tubule (PST) were dissected from rabbit kidneys, held with
      crimping pipettes in a chamber bathed in a buffered mannitol isosmotic solution
      (MBS, 295 mOsm/kg). Tubule cell volume changes with time (dV/Adt) after steps in
      MBS osmolality (delta Cs) were monitored on line with an inverted microscope, a
      TV camera and an image processor. Reflection coefficients sigma and osmotic
      permeability coefficients, Pos, for several solutes were measured using two
      methods. Method 1: sigma was calculated from the delta Csiso of impermeant and
      permeant solutes at which (dV/Adt)t-->0 = 0 (i.e., by a null point method). It is
      denoted as sigma 1. sigma 1 = 1.00 for mannitol (M), raffinose (R), sucrose (S),
      glycerol (G), acetamide (A) and urea (U). With formamide (F), sigma 1, Formamide
      = 0.62 +/- 0.05. These findings confirm our previous value of dp = 4.5 A for the
      diameter of the selectivity filter of the basolateral PST cell membrane water
      channel AQP1. Method 2: PST were exposed for 20 s to MBS made hyperosmotic by
      addition of a delta Cs of 35 mOsm/kg of R, S, M, G, A and U. Cells shrunk within
      500 ms of t = 0 to their osmometric volume and remained shrunk for the 20 s of
      the osmotic challenge. Pos was measured from the shrinking curves. P(os) = 3000
      +/- 25 microns/s with R, S, M, G, A and U. Method 2 also allowed to calculate
      sigma, denoted as sigma 2. sigma 2 = 1.00 for R, S, M, G, A and U. By contrast,
      the shrinking curve produced by a delta Cs of 35 mOsm/kg F was 1/5th to 1/6th
      slower and smaller (i.e., subosmometric) than that produced by a delta Cs of 35
      mOsm/kg R, S, M, G, A and U. Furthermore, with F cells did not remain shrunk but
      recovered their original volume within 3 s. P(os) (measured with F) is denoted as
      P(os)*, P(os)* = 480 +/- 30 microns/s. sigma 2, Formamide = 0.16 +/- 0.01. Use of
      sigma 1, sigma 2 and P(os)* values in Hill's equations for the bimodal theory of
      osmosis leads to n = 2-9. Where n is the number of water molecules single filling
      within the channel selectivity filter, whose length must lie within 6 to 27 A, a
      value significantly lower than our previous value calculated from the P(os)/Pd*
      ratio.

PMID- 9261990
TI  - Ca(2+)-dependent K+ channels in the cortical collecting duct of rat.
AB  - In the cortical collecting duct of the rat two Ca(2+)-dependent K+ channels have
      been described so far. In the luminal membrane a maxi K+ channel with a single
      channel conductance of 139 +/- 3 pS in excised membrane patches (n = 91) at 0 mV
      clamp voltage and asymmetrical KCl-concentrations in pipette and bath was found,
      while in the basolateral membrane an intermediate conductance K+ channel (85 +/-
      1 pS, n = 53) and a small K+ channel (28 +/- 2 pS, n = 15) was described. All
      these K+ channels had similar pharmacological properties since all could be
      blocked by the K+ channel inhibitors Ba2+, TEA+, and charybdotoxin. Verapamil,
      known as a L-type Ca2+ channel blocker, was also capable of inhibiting these K+
      channels. While the maxi K+ channel from the luminal membrane was upregulated by
      intracellular Ca2+ (EC50: 5 microM), the small and the intermediate K+ channel
      from the basolateral membrane were downregulated (IC50: 10 microM). When the
      cytosolic Ca(2+)-activity was in the physiological range below 1 microM the
      activity of the maxi K+ channel was low and regulated via intracellular pH and
      ATP. Furthermore, when CCD cells were strongly depolarized and under hypoosmotic
      stress, Ca2+ rose and activated this K+ channel, indicating that this channel is
      involved in volume regulation. Like the maxi K+ channel the intermediate
      conductance K+ channel from the basolateral membrane was also sensitive to
      intracellular changes of pH where acidic pH inhibited while alkaline pH activated
      this channel. But unlike the K+ channels from the luminal membrane the K+ channel
      from the basolateral membrane is not regulated by ATP up to 5 mM. The activity of
      the K+ channels from the basolateral membrane decreased steadily after excision
      of the membrane. This decrease could be prevented by applying cGMP and MgATP to
      the bath and thus, activating a membrane-bound cGMP-dependent protein kinase
      (PKG). The activation of the PKG could be reversed by its specific inhibitor
      KT5823 (1 microM). Due to the opposite regulation via intracellular Ca2+ and the
      involvement of different protein kinases a specific and independent regulation of
      K+ secretion and Na+ reabsorption is possible in the CCD of the rat.

PMID- 9261991
TI  - Tubule electrophysiology: from single channels back to the renal epithelium.
AB  - The "black box" study of the passive and active electrical properties of single
      barriers in renal tubules has greatly contributed to the understanding of renal
      ion transport. With the advent of patch-clamp technology, it is feasible to
      record the ion flow through single channel proteins of the kidney, to infer their
      ion selectivity, gating properties, open pore conductivity, and to study directly
      the regulatory domains or sensors that control the gating of renal ion channels.
      Accordingly, it should be possible to upscale these microscopic parameters and
      predict the macroscopic membrane properties of renal membranes, using the
      knowledge of the microscopic single channel current (ij) for ion "j" under a
      physiologic driving force, the average number of channels in a single membrane
      patch (N), the open probability of a single channel (P(o)), the incidence of
      finding a channel in a population of membrane patches (f), and the area of a
      typical membrane patch (a). The experimental errors in the determination of each
      of these microscopic parameters are discussed. On the other hand, the macroscopic
      membrane properties of renal tubule cells cannot be reliably obtained from
      measurements of whole-cell patch-clamp, because of the polarized distribution of
      the dissipative electrical properties within a renal cell. The asymmetrical
      distribution of channel types, channel density and channel kinetics, between the
      apical and the basolateral membrane, precludes the use of the whole-cell
      conductance as the macroscopic reference. Instead, classical equivalent circuit
      analysis of renal epithelia is still necessary to obtain cell membrane parameters
      that validity represent the ensembles of single channels.

PMID- 9261992
TI  - In vitro 6 beta-hydroxylation of progesterone in human renal tissue.
AB  - Increased levels of 6 beta-hydroxylated steroids have been found in the urine of
      several species under different physiological and pathophysiological conditions.
      Until now, liver, adrenal glands and placenta have been identified as organs
      which contain 6 beta-hydroxylase activity. However, it has not yet been
      established whether 6 beta-hydroxylation occurs in mammalian kidney. In this
      study we have performed in vitro studies with preparations from rat and human
      kidney cortex and have obtained evidence for the presence of a small but
      significant renal 6 beta-hydroxylation activity. Two points deserve to be
      mentioned: 1) A species difference is documented by the presence of the enzyme in
      human, but not in rat kidney; 2) Substrate specificity is evident. Progesterone,
      but not corticosterone, was transformed to the 6 beta-hydroxylated metabolite in
      human tissue. The biological significance of the 6 beta-hydroxylation of
      endogenous, as well as exogenous steroids could be that 6 beta-hydroxylation
      opens an alternate route of progesterone metabolism in parallel to other
      conversion and/or degradation pathways. Furthermore, since other 6 beta
      hydroxylated steroids have been reported to exert biological effects, this may
      also be the case with 6 beta-hydroxy progesterone.

PMID- 9261993
TI  - New types of K+ channels in the colon.
AB  - The mechanism of epithelial Cl- secretion requires K+ recycling via basolateral
      ion channels. Two types of K+ channels were identified. A Ca(2+)-activated, and a
      very small cAMP-regulated K+ channel. Increase of cAMP inhibits the Ca(2+)
      activated K+ channel and thus makes small K+ channel the limiting step for cAMP
      dependent Cl- secretion.

PMID- 9261994
TI  - The start of clinical nephrology in Austria and developments in the treatment of
      patients with end stage renal disease over the last decades.
AB  - Over the last 50 years nephrology has seen milestone achievements in basic
      sciences as well as in clinical medicine. This article describes the start of
      clinical nephrology in Austria in the 1950's and the significant changes over the
      last decades. With 625 patients/pmp Austria has worldwide one of the highest
      numbers of patients treated for endstage renal disease. In 1995, 5020 patients
      were alive on replacement therapy, equally distributed between transplanted and
      dialyzed patients. An overview over the developments that led to Austria's
      prominent role in the treatment of end stage renal disease is given.

PMID- 9261995
TI  - Lose salt and gain a friend! A tribute to Gerhard Giebisch.
AB  - In this little essay I describe recent advances in understanding the problem of
      salt sensitivity and salt resistance involved in the control of blood volume and
      blood pressure. Genetic evidence links the recently characterized epithelial
      sodium channel (ENaC) and the potassium channel (ROMK-1) to monogenic diseases in
      humans, characterized by a renal salt-losing syndrome. A loss of function
      mutations in ROMK-1 gene causes in some pedigrees the syndrome of Bartter,
      characterized by metabolic alkalosis and a severe salt-losing syndrome. A loss of
      function mutations in ENaC genes causes pseudohypoaldosteronism-type 1,
      characterized by hypovolaemia, hyperkaliaemia, metabolic acidosis and
      hypotension. ENaC and ROMK-1 are expressed in the apical membrane of principal
      cells of the cortical collecting duct and their role in Na/K balance is briefly
      reviewed.

PMID- 9261996
TI  - beta-Agarase from Pseudomonas sp. W7: purification of the recombinant enzyme from
      Escherichia coli and the effects of salt on its activity.
AB  - The recombinant plasmid (pJAI), harbouring the agarase gene (pjaA) of Pseudomonas
      sp. W7, was introduced and expressed in Escherichia coli JM83. The agarase was
      purified using a combination of acetone precipitation and anion-exchange, gel
      filtration and affinity chromatographies, with overall yield of 10% from the
      culture supernatant of E. coli JM83 (pJAI). The purified agarase migrated as a
      single band (molecular mass 59 kDa) on SDS/PAGE and was found to be beta-agarase,
      which could hydrolyse the beta-1,4 linkage of agarose to yield neoagarotetraose
      as the main product. Optimal enzyme activity was at pH 7.8 and the temperature
      optimum spanned the broad range 20-40 degrees C. The recombinant agarase was
      halophilic, maximum activity being exhibited at 0.9 M NaCl. This halophilic
      property could improve the production of neoagaro-oligosaccharides available in a
      marine environment.

PMID- 9261997
TI  - A new method of synthesizing biopolymeric affinity ligands.
AB  - (1) A new concept for producing soluble polymeric affinity ligands is proposed
      and exemplified. By solid-phase synthesis, an insoluble hydrophilic polymer is
      converted into an affinity gel. The gel is hydrolytically degraded to water
      soluble affinity polymeric ligands which are recovered and purified. (2) A water
      soluble biopolymeric metal-affinity carrier based on an iminodiacetic acid (IDA)
      derivative of dextran has been synthesized through the modification of Sephadex G
      200 by IDA, followed by hydrolysis with dextranase and size-exclusion
      chromatographic purification of the high-molecular-mass fragments. (3) The
      molecular size of the soluble products as a function of hydrolysis time with
      dextranase from Penicillium sp. was determined. The range of molecular size of
      the biopolymeric chelating ligand varies from around 200 Da to greater than 580
      kDa. (4) The influence of three metal ions chelated with the Sephadex derivative
      on the hydrolysis rate and the molecular-size distribution of end products was
      studied. Eu3+ was found to improve the rate of solubilization. Ni2+ and Cu2+
      decreased the hydrolysis rate, as compared with that of the metal-free IDA
      Sephadex. (5) The method introduced here has the potential of being developed and
      applied as a general technology for synthesis of soluble multifunctional affinity
      ligands. Such ligands should be useful for liquid-phase extraction as well as for
      the synthesis of adsorbents with localized multiple binding sites. Other possible
      fields of applications are to be found in medicine, where they could be used for
      slow drug delivery or detoxification, and in analytical chemistry, where they
      could be used in various assays.

PMID- 9261998
TI  - Expression in Escherichia coli and purification of human thrombopoietin.
AB  - Human thrombopoietin (TPO) has been successfully overexpressed in Escherichia
      coli, with an expression level of about 12% of total cellular protein. The full
      length TPO gene was subcloned into the prokaryotic expression vector pKK233-2
      under the control of the inducible tac promoter. The recombinant protein was
      produced mainly in the form of inclusion body. By efficient renaturation and one
      step purification, the recombinant protein was purified to homogeneity. The
      specific activity and yield of recombinant TPO can reach 2 x 10(4) units/mg and 2
      mg/g of wet E. coli cells respectively.

PMID- 9261999
TI  - Some biochemical properties and the classification of a range of bacterial
      haloalkane dehalogenases.
AB  - Multivariate analyses and experimental data have been used to evaluate the
      relationships between eight bacterial hydrolytic haloalkane dehalogenases. The
      results indicate that seven of the dehalogenases investigated can confidently be
      placed into two Classes [sensu Slater, Bull and Hardman (1995) Biodegradation 6,
      181-189] according to their substrate profiles. The remaining enzyme, isolated
      from Rhodococcus erythropolis CP9, appears to represent a third Class of
      haloalkane dehalogenases.

PMID- 9262000
TI  - An efficient cost-effective protocol for automated fluorescent-DNA sequencing.
AB  - A simple and cost-effective method is described to sequence double-stranded DNA
      (< 100 ng) using a very small amount of fluorescent sequencing mix (one-tenth of
      manufacturer-recommended amount). The modification has significant advantages
      over conventional protocols and can be used to sequence, using a single
      sequencing kit, at least ten times the number of samples. This modified method
      also removes the post-reaction cleaning protocol and can be used for direct
      loading of samples on gels after completion of sequencing reactions. The accuracy
      of DNA sequencing data from analysis of 700 to 750 nucleotides is greater than
      98.5%.

PMID- 9262001
TI  - Activity and stability of a Rhizomucor miehei lipase in hydrophobic media.
AB  - The effects of detergents and organic solvents on a commercial lipase (Lipozyme)
      from Rhizomucor miehei were investigated. It was shown that the detergent sodium
      cholate is possibly an activator of the enzyme, increasing lipase activity 2.5
      times (250% of the control) when the enzyme was preincubated with 7 mM cholate.
      Lipozyme activity was over twice as high (230% of the control) in the presence of
      80 mM Tween 80 or 90 mM Tween 20 (polyoxyethylenesorbitan monolaurate),
      apparently through an additional emulsifying action on the substrate.
      Preincubation with Tween 80 (polyoxyethylenesorbitan mono-oleate) did not affect
      enzyme activity. In contrast, lipase activity was completely inhibited in the
      presence of an 8.9 mM concentration of another non-ionic detergent, Brij 58,
      whereas with a 16.4 mM concentration of the cationic detergent
      cetyltrimethylammonium bromide (CTAB), enzyme activity was reduced by 80%.
      Preincubation of Lipozyme with the same concentrations of Brij 58
      [poly(oxyethylene)20 cetyl ether] and CTAB promoted total inactivation of the
      enzyme. Organic solvents had different effects on lipase activity and stability.
      Of the tested solvents, hexane was least deleterious to lipase activity and did
      not alter enzyme stability on preincubation. These results suggest that Lipozyme
      can be used in esterification reactions with hexane as solvent or in hydrolysis
      reactions with Tween 20 or Tween 80 as emulsifying agents, after pretreatment
      with sodium cholate.

PMID- 9262002
TI  - Use of the HIV-1 protease for excision of growth-hormone-releasing factor from
      synthetic and recombinant peptide precursors.
AB  - An autolysis-resistant mutant of the HIV-I protease was employed for removal of
      metabolically stabilized and highly bioactive analogues of bovine growth-hormone
      releasing factor (bGRF) from their larger either synthetic or recombinant
      precursors. The N-terminal four amino acids in two selected model GRF analogues,
      Y1IDAIFTSSYRKVLAQLSARKLLQDILSRQVF32-OH (I; GRF32) and
      Y1IDAIFTSSYRKVLAQLSARKLLQDILSRQ30-OH (IA; GRF30), conform well to the specificity
      of the HIV-I protease for residues in the P1' to P4' positions of its peptide
      substrates. A variety of amino acids were tried in the N-terminal extension
      (positions P4-P1) to fit the protease substrate specificity for the 8 amino acids
      in positions P4-P4'. A synthetic precursor of I, extended N-terminally with RQVF
      , a sequence representing the four C-terminal residues in I, was effectively
      cleaved by the protease at the Phe-1-Tyr1 bond (... RQVF-decreases-YIDA ...) to
      release GRF32. However, when several soluble fusion proteins linked to GRF32 by
      the RQVF sequence were expressed in Escherichia coli, attempts to cleave out the
      core GRF32 met with variable, and only limited, success. By random mutagenesis in
      a propeptide segment, [MGQSVAQVF]-decreases-GRF30, (II) was identified as a
      construct that showed reasonably high-level expression in E. coli and was
      effectively processed by the HIV-I protease. A yield of 5 mg of pure GRF30 was
      obtained/litre of culture medium after a single HPLC purification step.

PMID- 9262003
TI  - Enhancement of cyclodextrin production through use of debranching enzymes.
AB  - In the presence of a complexant and a debranching enzyme capable of cleaving
      alpha-(1-->6) linkages in alpha-D-glucans, Bacillus mascerans cyclodextrin
      glucanotransferase (CGTase; EC 2.4.1.19) converted starch, maltodextrin and
      glycogen into cyclodextrin (CD) in yields higher than those obtainable in the
      absence of debranching enzyme. The extent of yield enhancement by pullulanase (EC
      3.2.1.41; from Enterobacter aerogenes) was dependent upon temperature, type of
      substrate (including source of starch) and kind of complexant. Highest yields
      with pullulanase were attained generally by use of low temperature (15-25 degrees
      C) and starches of low amylose content. At 25 degrees C and pH 7, with
      cyclodecanone as complexant, 91-93% yields of beta-CD were obtainable from
      amylopectin, waxy-maize starch, and tapioca starch. With decan-I-ol as
      complexant, amylopectin was converted at 15 degrees C into alpha-CD in 84% yield.
      With cyclotridecanone as complexant, amylopectin was converted at 40 degrees C
      into gamma-CD in 72% yield. The debranching enzyme isoamylase (EC 3.2.1.68; from
      Pseudomonas amyloderamosa) was also employed successfully to achieve high beta-CD
      yields. A 90% yield of beta-CD from amylopectin was obtained by applying
      isoamylase, CGTase and cyclodecanone at pH 6 and 25 degrees C.

PMID- 9262004
TI  - Isolation and characterization of the high-density lipoproteins from the
      hemolymph and ovary of the penaeid shrimp Penaeus semisulcatus (de Haan):
      apoproteins and lipids.
AB  - The high-density lipoproteins (HDLs) found in the male and female hemolymph of
      Penaeus semisulcatus de Haan were isolated by NaBr (1.22 g/ml) followed by
      sucrose gradient (5-25%) ultracentrifugation. The male HDL contained one protein,
      lipoprotein 1 (LP1), composed of one 110-kDa peptide subunit. The female HDL
      contained two proteins: 1) the LP1 that was immunoidentical to the male LP1 and
      was similarly composed of one 110-kDa peptide subunit and 2) vitellogenin (Vg),
      reacting positively with the rabbit antiserum generated against vitellin (Vt)
      that was isolated from vitellogenic ovaries. Both Vg and Vt consisted mainly of
      three polypeptide subunits (200, 120, and 80 kDa) as revealed by denatured PAGE
      and Western blot. The LP1 from males or females did not react with the Vt rabbit
      antiserum. Similarly, Vg and Vt did not react with the rabbit antiserum prepared
      against LP1. Phospholipids (PL) constituted 71-76% of the total lipids in the
      hemolymph and HDLs of both male and female hemolymph. Cholesterol (Ch) amounted
      to 17-20%, and small amounts (5%) of diacylglycerols (DAG) were also carried by
      these HDLs. Both the PL and DAG contained highly unsaturated fatty acids (20:5
      omega 3 and 22:6 omega 3) that are transported from the food or hepatopancreas to
      the tissues, including the vitellogenic ovaries in females. In the present study
      we show for the first time the separate lipid composition of female LP1 and Vg
      and compare them with the lipids attached to the Vt. Vg had a lower lipid content
      than LP1 (540 and 1089 mg/g protein, respectively). Differences were also found
      in the relative abundance of PL, Ch, and DAG classes in the LP1 in comparison
      with Vg. Furthermore, small amounts (approximately 3.8%) of triacylglycerols
      (TAG) were found only in the hemolymph of vitellogenic females, and they were
      associated with the Vg. Although Vg and Vt were composed of similar polypeptides,
      their lipid composition was different Vt, in contrast to Vg, carried considerable
      amounts of TAG (approximately 22%) and only trace amounts of DAG. The
      significance of the TAG in the hemolymph of vitellogenic females is not known,
      and the functional relationship between Vg and Vt requires future extensive
      studies. Lipids were not detected in hemocyanin that was purified from clotted
      hemolymph.

PMID- 9262005
TI  - Water distribution and permeability of zebrafish embryos, Brachydanio rerio.
AB  - Teleost embryos have not been successfully cryopreserved. To formulate successful
      cryopreservation protocols, the distribution and cellular permeability to water
      must be understood. In this paper, the zebrafish (Brachydanio rerio) was used as
      a model for basic studies of the distribution to permeability to water. These
      embryos are a complex multi-compartmental system composed of two membrane-limited
      compartments, a large yolk (surrounded by the yolk syncytial layer) and
      differentiating blastoderm cells (each surrounded by a plasma membrane). Due to
      the complexity of this system, a variety of techniques, including magnetic
      resonance microscopy and electron spin resonance, was used to measure the water
      in these compartments. Cellular water was distributed unequally in each
      compartment. At the 6-somite stage, the percent water (V/V) was distributed as
      follows: total in embryo = 74%, total in yolk = 42%, and total in blastoderm =
      82%. A one-compartment model was used to analyze kinetic, osmotic shrinkage data
      and determine a phenomenological water permeability parameter, Lp, assuming
      intracellular isosmotic compartments of either 40 or 300 mosm. This analysis
      revealed that the membrane permeability changed (P < 0.05) during development.
      During the 75% epiboly to 3-somite stage, the mean membrane permeability remained
      constant (Lp = 0.022 +/- 0.002 micron x min-1atm-1 [mean +/- S.E.M.] assuming
      isosmotic is 40 mosm or Lp = 0.049 +/- 0.008 micron x min-1atm-1 assuming
      isosmotic is 300 mosm). However, at the 6-somite stage, Lp increased twofold (Lp
      = 0.040 +/- 0.004 micron x min-1atm-1 assuming isosmotic is 40 mosm or Lp = 0.100
      +/- 0.017 micron x min-1atm-1 assuming isosmotic is 300 mosm). Therefore, the low
      permeability of the zebrafish embryo coupled with its large size (and consequent
      low area to volume ratio) led to a very slow osmotic response that should be
      considered before formulating cryopreservation protocols.

PMID- 9262006
TI  - Simulated hibernation of sea turtles in the laboratory: I. Feeding, breathing
      frequency, blood pH, and blood gases.
AB  - Captive immature green (Chelonia mydas) and Kemp's ridley (Lepidochelys kempi)
      sea turtles were examined to determine if a hibernation-like state could be
      induced under controlled conditions. Both species demonstrated that they are able
      to acclimate to cold temperatures behaviorally. However, the two species appeared
      to respond differently to decreasing temperature. Whereas the green turtles
      tolerated the onset of cold water temperatures by reducing swimming activity, the
      ridleys became very agitated and active as they were exposed to temperatures
      below 20 degrees C. Nevertheless, both species displayed semi-dormant behavior at
      temperatures below 15 degrees C, coming to the surface to breathe periodically at
      intervals of up to three hours. At low temperatures, venous blood pO2 and pCO2
      decreased, whereas venous blood pH increased. Feeding also decreased as either
      species was exposed to cold temperature: greens (at 15 degrees C) and ridleys (at
      20 degrees C) decreased food consumption to 50% of control levels, and ceased
      feeding below 15 degrees C. Thus, these species tolerated temperature drops and
      the associated hypophagia. They did not exhibit cold-stunning behavior, as has
      been observed in wild sea turtles exposed to rapid temperature drops, or
      prolonged periods of hibernation-like dormancy, as has been proposed for wild sea
      turtles during cold winter months.

PMID- 9262007
TI  - Ca2+ activated myosin-ATPase in cardiac myofibrils of rainbow trout, freshwater
      turtle, and rat.
AB  - The Ca(2+)-activated myosin-ATPase and its dependence on hypoxia were assessed in
      freshwater turtle, rainbow trout, and in some cases rat. At 20 degrees C and pH
      7.3, the maximal ATPase activity was (mean +/- SEM): turtle 0.040 +/- 0.003,
      trout 0.090 +/- 0.005, and rat 0.12 +/- 0.004 mmol*min-1*g-1 myofibrillar dry
      weight. The turnover number was about three times lower for turtle than for
      trout. Trout is typically active at lower temperatures than turtle, and its
      myosin-ATPase activity was about three times lower at 10 degrees than at 20
      degrees C. Addition of 12 mM phosphocreatine showed that the myosin-ATPase
      activity covered by myofibrillar creatine kinase was 22 +/- 2% for turtle, 14 +/-
      2% for trout, and 69 +/- 5% for rat. At pH 6.8 relative to 7.3, the maximal M
      ATPase activity was the same, whereas the Ca(2+)-sensitivity decreased, and more
      so for trout than for turtle. This difference disappeared, when trout myocardium
      was examined at 10 degrees C. P(i) (15 mM) affected neither maximal activity nor
      Ca(2+)-sensitivity. ADP, however, reduced maximal myosin-ATPase activity, and
      more so in trout than in turtle. In conclusion, the "slow"-type myosin, the low
      sensitivity of acidification and ADP, and the high creatine kinase/myosin-ATPase
      ratio in turtle relative to trout accord with the well-known ability of turtle
      myocardium to work during hypoxia. However, the difference in living temperature
      between turtle and trout obscures the situation (e.g. inclusion of rat data
      suggests that the creatine kinase/myosin-ATPase ratio is related to temperature.

PMID- 9262008
TI  - Effects of embryonic estrogen on differentiation of the gonads and secondary
      sexual characteristics of male zebra finches.
AB  - Male zebra finches sing to court females, whereas females do not normally sing.
      In parallel, the telencephalic brain regions that control song are larger in
      volume and contain larger cells in males than in females. The vocal control organ
      (syrinx) is also larger in males. Some evidence suggests that the sexual
      differentiation of both anatomy and behavior is under the regulation of gonadal
      hormones during early development, yet recent data conflict with the idea that
      the sole source of masculinization of the neural song system is the testes. In
      the present experiment, we treated genetic males with estradiol benzoate on
      embryonic day 5 and measured the volume of and neuron soma size in robust nucleus
      of the archistriatum (RA) and the high vocal center (HVC), two telencephalic song
      control nuclei. We also weighed the syrinx, the muscles of which are the target
      of the motor pathway containing the two brain regions. The estrogen treatment
      disrupted testicular morphology, and induced an oviduct in six of seven animals,
      but it had no effect on any of four measures of masculinization of the neural
      song system. These results suggest that normal testicular tissue is not required
      for masculine development of the neural song system.

PMID- 9262009
TI  - Involvement of chloride channels in progesterone production during meiotic
      maturation of follicle-enclosed oocytes of Rana temporaria and Xenopus laevis.
AB  - The chloride channel blockers SITS (4-acetamido-4'-isothiocyanostibene-2,2'
      disulphonic acid) and DIDS (4,4'-diisothiocyanostilbene-2,2'-disulphonic acid)
      markedly suppressed progesterone production in the Rana temporaria and Xenopus
      laevis follicle-enclosed oocytes and oocyte maturation stimulated by the
      homologous pituitary suspension and hCG, respectively. Inhibition was dose
      dependent and decreased with the increase of the hormone concentration. SITS did
      not affect progesterone production in the R. temporaria follicle-enclosed oocytes
      stimulated by dbcAMP. Substitution of sodium chloride for equimolar
      concentrations of sodium gluconate, methanesulfonate, glutamate, or formate
      significantly potentiated the gonadotropin-stimulated progesterone production and
      oocyte maturation in the both species. Possible involvement of chloride channels
      in progesterone production by the gonadotropin-stimulated amphibian follicle
      enclosed oocytes is discussed.

PMID- 9262010
TI  - Gene flow and genetic diversity in naturally fragmented metapopulations of deep
      sea hydrothermal vent animals.
AB  - The ephemeral nature of deep-sea hydrothermal vents is expected to favor species
      with good colonization abilities, high dispersal rates, and rapid individual
      growth rates. Studies of gene flow in vent-endemic species provide glimpses into
      modes and patterns of dispersal. For some species, gene flow occurs without
      geographical bias (i.e., island model); their dispersal capabilities probably
      exceed the sampled geographical range. For other species, genetic differentiation
      increases with geographical distance (isolation-by-distance model) and suggests a
      stepping-stone mode of dispersal between neighboring vents. Genetic subdivision
      in a third group of species is associated with geographical offsets between
      contiguous segments of a ridge axis. These species all possess a free-living
      larval stage and average rates of gene flow (Nm) exceeding the critical value of
      one. In contrast, an amphipod that broods its young shows evidence for isolation
      by-distance along a ridge axis and nearly complete isolation between distinct
      ridge axes. Early successional species (i.e., those that rapidly establish
      populations at nascent vents) also have high levels of genetic variability that
      probably results from a larger global population size. Bivalve species, which are
      restricted to a few of the known vent sites, appear at a later successional stage
      and have lower levels of variability. The relative successional position (early
      versus late) and overall abundance of a species may play significant roles in
      determining the retention of genetic diversity in populations inhabiting these
      ephemeral environments.

PMID- 9262012
TI  - Effective number of breeding adults in Bufo bufo estimated from age-specific
      variation at minisatellite loci.
AB  - Estimates of the effective number of breeding adults were derived for three semi
      isolated populations of the common toad Bufo bufo based on temporal (i.e. adult
      progeny) variance in allele frequency for three highly polymorphic minisatellite
      loci. Estimates of spatial variance in allele frequency among populations and of
      age-specific measures of genetic variability are also described. Each population
      was characterized by a low effective adult breeding number (Nb) based on a large
      age-specific variance in minisatellite allele frequency. Estimates of Nb (range
      21-46 for population means across three loci) were approximately 55-230-fold
      lower than estimates of total adult census size. The implications of low
      effective breeding numbers for long-term maintenance of genetic variability and
      population viability are discussed relative to the species' reproductive ecology,
      current land-use practices, and present and historical habitat modification and
      loss. The utility of indirect measures of population parameters such as Nb and Ne
      based on time-series data of minisatellite allele frequencies is discussed
      relative to similar measures estimated from commonly used genetic markers such as
      protein allozymes.

PMID- 9262011
TI  - The effects of habitat fragmentation on the genetic structure of small mammal
      populations.
AB  - We present five case studies highlighting the effects of habitat fragmentation on
      the genetic structure of small mammal populations. The studies reflect different
      spatial scales and components of genetic variation. In marginal and central
      populations of Sigmodon hispidus we found less allozymic variation within the
      marginal population, whereas patterns of morphological variability were the
      converse. In the rice rat (Oryzomys spp.), nucleotide diversity in mtDNA was
      similar in an island population in the Florida Keys to mainland populations in
      the Everglades. This observation contrasts with insular vole populations
      (Microtus spp.), where isolation on islands results in genetic structuring.
      Temporal changes in abundance in mainland populations had no effects on genetic
      differentiation (FST values) because subpopulations did not experience
      bottlenecks. In an experimentally fragmented landscape, fragmentation influenced
      demographic processes but not genetic structure. We conclude that (1) with
      extreme fragmentation, small mammal populations become depauperate of genetic
      variation and differentiate genetically; (2) different components of genetic
      variation lead to different genetic structuring; (3) spatial and temporal scales
      should both be considered when examining genetic structure of populations; (4)
      demographic and ecological processes are more likely influenced by fragmentation
      than genetic structure; and (5) there is an interaction between demographic
      processes and genetic structure.

PMID- 9262013
TI  - Lack of concordance between mtDNA gene flow and population density fluctuations
      in the bank vole.
AB  - The genetic structure of bank voles Clethrionomys glareolus was determined from
      analyses of mitochondrial DNA (mtDNA) sequences, and compared with previous data
      on geographical synchrony in population density fluctuations. From 31 sample
      sites evenly spaced out along a 256-km transect in SE Norway a total of 39
      distinct mtDNA haplotypes were found. The geographical distribution of the
      haplotypes was significantly non-random, and a cladistic analysis of the
      evolutionary relationship among haplotypes shows that descendant types were
      typically limited to a single site, whereas the ancestral types were more widely
      distributed geographically. This geographical distribution pattern of mtDNA
      haplotypes strongly indicates that the range and amount of female dispersal is
      severely restricted and insufficient to account for the previously observed
      synchrony in population density fluctuations. We conclude that geographical
      synchrony in this species must be caused by factors that are external to the
      local population, such as e.g. mobile predators.

PMID- 9262014
TI  - Molecular markers reveal differentiation among isolates of Coccidioides immitis
      from California, Arizona and Texas.
AB  - Coccidioides immitis causes coccidioidomycosis, a fungal disease of both immuno
      compromised and otherwise healthy people; it is capable of causing large
      epidemics and the disease is often refractory to chemotherapy. To quantify the
      magnitude of population differentiation and estimate levels of gene flow in C.
      immitis, multilocus genotypes were scored for 20-25 clinical isolates from each
      of Bakersfield (California), Tucson (Arizona), and San Antonio (Texas). The
      molecular markers used were PCR products with polymorphic restriction
      endonuclease sites, found and characterized in a previous study of the Tucson
      population. The data show very highly significant differences in allele
      frequencies between all three populations, and suggest very low levels of
      migration between populations. One isolate in the San Antonio sample was an
      outlier, showing the California-specific allele at all four of the loci
      distinguishing the two populations, and subsequent inquiries indicated that the
      infection had indeed been acquired in California. Thus, genetic information can
      be used to infer the geographical origin of a fungal infection.

PMID- 9262015
TI  - Characterization of microsatellite loci from the socially monogamous lizard
      Tiliqua rugosa using a PCR-based isolation technique.

PMID- 9262017
TI  - The development of field-emission scanning electron microscopy for imaging
      biological surfaces.
AB  - This article traces the important milestones in the development of high
      resolution, field-emission, scanning electron microscopes (SEM). Such instruments
      are now capable of producing images of the surfaces of biological specimens that
      rival, in terms of resolution and contrast, those produced by conventional
      transmission electron microscopy (TEM). Even though one of the first instruments
      to produce a useful transmission electron microscope image was, in fact, an early
      scanning microscope, TEM reached its full potential for biological imaging almost
      30 years sooner than did SEM. The main reason for this slow rate of development
      is the dependence of any scanning technique on source brightness. The only
      suitable electron source was the field-emission source, originally developed in
      the 1930's. Making this into a stable and reliable electron source for microscopy
      required many technical barriers to be overcome. An additional delay may have
      been caused by the great success that attended the introduction of early SEM
      instruments. These instruments which employed heated, tungsten hairpin cathodes,
      were inexpensive and reliable, but they that were also far from optimal in terms
      of optical performance. Their market success may have engendered the sense of
      inertia and complacency that further delayed the introduction of low aberrations
      objective lenses and field-emission sources for almost 20 years after they were
      first introduced to electron microscopy. In addition, the fact that these early
      SEMs accustomed users to operating with a much higher beam voltage than was
      either necessary or wise, lead many to assume that the SEM was incapable of
      producing high-resolution images of biological surfaces. This left them open to
      fascination with newer ahd slower techniques that, on balance, were less suitable
      than optimized SEM for most of their imaging needs. In parallel to these
      developments in instrumentation, major improvements were also made in the way
      that the specimen surface was prepared before placing it into the vacuum and
      radiation environment of the microscope.

PMID- 9262016
TI  - Isolation and characterization of simple sequence repeats in the genome of the
      common shrew.

PMID- 9262018
TI  - Double-layer coating for field-emission cryo-scanning electron microscopy-
      present state and applications.
AB  - Imaging of fast-frozen samples is the most direct approach for electron
      microscopy of organic material. It prevents chemical fixation and drying
      artifacts. Frozen samples can be replicated and imaged in the transmission
      electron microscope (TEM), or they can be directly visualized in the cryo
      scanning electron microscope (cryo-SEM). Double-layer coating combines these two
      techniques and many of their advantages. With this method, the frozen bulk sample
      is coated similar to the TEM-replica technique with, for example, a shadow of
      platinum (at an angle of 45 degrees) and an additional layer of carbon. Then, the
      sample is cryo-transferred to an SEM equipped with a cold stage and imaged with
      the material-dependent backscattered electron signal that shows the platinum
      distribution. With this method, charging artifacts and the effects of beam damage
      are significantly reduced. Although currently the resolution of the replica
      technique cannot be surpassed, the method greatly facilitates the processing of
      brittle, rapidly frozen samples because no replica cleaning is necessary. This
      makes the method especially suitable for high-pressure frozen samples.

PMID- 9262019
TI  - High-resolution cryo-scanning electron microscopy study of the macromolecular
      structure of fibronectin fibrils.
AB  - High-resolution cryo-scanning electron microscopy was used to examine fibronectin
      fibrils formed in culture by human skin fibroblasts and in a cell-free system by
      denaturing soluble plasma fibronectin with guanidine. These studies indicate that
      the conformation of fibrils formed in culture and in a cell-free system appeared
      to be similar and that fibronectin fibrils have at least two distinct structural
      conformations. Fibronectin fibrils can be very straight structures with smooth
      surfaces or highly nodular structures. The average diameter of the nodules in
      these fibrils is 12 nm. Both conformations can be seen within an individual
      fibril indicating that they are not different types of fibronectin fibrils but
      rather different conformational states. Immunolabeling studies with a monoclonal
      antibody, IST-2, to the heparin II binding domain of fibronectin revealed that
      the epitope was buried in highly smooth fibrils, but it was readily exposed in
      nodular fibrils. We propose, therefore, that fibronectin fibrils are highly
      flexible structures and, depending on the conformation of the fibril, certain
      epitopes on the surface may be buried or exposed.

PMID- 9262021
TI  - The fine structure of fenestrated adrenocortical capillaries revealed by in-lens
      field-emission scanning electron microscopy and scanning transmission electron
      microscopy.
AB  - Cell biologists probing the physiologic movement of macromolecules and solutes
      across the fenestrated microvascular endothelial cell have used electron
      microscopy to locate the postulated pore within the fenestrae. Prior to the
      advent of in-lens field-emission high-resolution scanning electron microscopy
      (HRSEM) and ultrathin metal coating technology, quick-freeze, platinum-carbon
      replica and grazing thin-section transmission electron microscopy (TEM) methods
      provided two-dimensional or indirect imaging methods. Wedge-shaped octagonal
      channels composed of fibrils interwoven in a central mesh were depicted as the
      filtering structures of fenestral diaphragms in images of platinum replicas
      enhanced by photographic augmentation. However, image accuracy was limited to
      replication of the cell surface. Subsequent to this, HRSEM technology was
      developed and provided a high-fidelity, three-dimensional topographic image of
      the fenestral surface directly from a fixed and dried bulk adrenal specimen
      coated with a 1 nm chromium film. First described from TEM replicas, the "flower
      like" structure comprising the fenestral pores was readily visualized by HRSEM.
      High-resolution images contained particulate ectodomains on the lumenal surface
      of the endothelial cell membrane. Particles arranged in a rough octagonal shape
      formed the fenestral rim. Digital acquisition of analog photographic recordings
      revealed a filamentous meshwork in the diaphragm, thus confirming and extending
      observations from replica and grazing section TEM preparations. Endothelial cell
      pockets, first described in murine renal peritubular capillaries, were observed
      in rhesus and rabbit adrenocortical capillaries. This report features recent
      observations of fenestral diaphragms and endothelial pockets fitted with multiple
      diaphragms utilizing a Schottky field-emission electron microscope. In-lens
      staging of bulk and thin section specimens allowed tandem imaging in HRSEM and
      scanning TEM modes at 25 kV.

PMID- 9262020
TI  - High-resolution backscatter electron detection of cell surface molecules on human
      platelets using the double-layer coating method and cryo field emission scanning
      electron microscopy.
AB  - A model system utilizing cryo scanning electron microscopy (SEM) for the
      detection of putative cell adhesion molecule(s) on the surface of human platelets
      is described. Plunge freezing was used for cryoimmobilization of unactivated and
      activated platelets after prefixation. Extracellular ice was removed by
      sublimation to expose the surface of the platelet membrane. Cryosamples were
      coated by the double-layer method, in which undirectional shadowing is performed
      at an angle of 45 degrees with 2 nm of platinum by thermal evaporation, followed
      by evaporation of 5 nm of carbon at an angle of 90 degrees for stabilization of
      the platinum film. The topography of the extracellular surface of the
      unstimulated platelet membrane was dominated by small spherical protrusions,
      while that of the activated platelet had not only similar spherical projections,
      but also possessed numerous rod-like protrusions, presumably representing the
      upregulation of the cell adhesion molecule, P-selectin, from intracellular a
      granules. These results clearly demonstrate that cryo field-emission SEM can
      detect molecular topography on the extracellular surface of cells consistent with
      the dimensions and shape of membrane cell adhesion molecules.

PMID- 9262022
TI  - High-resolution field-emission scanning electron microscopy of nuclear pore
      complex.
AB  - The nuclear pore complex (NPC) is a large macromolecular assembly inserted into
      the nuclear envelope (NE). It controls the traffic of proteins, RNA, and RNA
      proteins between nucleus and cytoplasm. It chemical composition and function are
      now intensively investigated in many organisms. To understand this unique
      membrane transport system, we must know the supramolecular organization of the
      NPC. In recent years, high-resolution field-emission scanning electron microscopy
      has made important contributions to our knowledge of NPC structure. It provided
      the first images of the complex and beautiful fish trap-like structure of its
      intranuclear surface, documented in this review. It also has provided the first
      images of a new intranuclear structure, a system of branching hollow cables
      connecting the nuclear interior with the NPCs at the nuclear surface. Most likely
      this is an intranuclear transport system, assuring efficient exchange between the
      nuclear interior and the NE, especially in large nuclei.

PMID- 9262023
TI  - Improved common line-based icosahedral particle image orientation estimation
      algorithms.
AB  - Modifications are described for the center and angular parameter estimation
      algorithms of common line-based particle image orientation determination which is
      an essential step in the three-dimensional reconstruction of icosahedral virus
      particles. The modifications incorporate a variety of image processing, pattern
      recognition, and statistical tools resulting in objective and automated
      orientation estimation algorithms. The modified algorithms were tested using
      electron cryo-microscopic particle images of three different virus specimens,
      with sizes 400-1250 A in diameter, covering a broad range of defocus values.
      Evaluation of these modified algorithms shows significant improvement over the
      previous algorithms. The center and angular parameters were estimated with higher
      accuracy allowing the identification of a larger number of particle orientations.
      Usage of the modified estimation algorithms resulted in the identification of
      particle orientations which could not to be identified using the algorithms
      before modification. Furthermore, these improvements have resulted in the
      determination of a better quality and a higher resolution three-dimensional
      reconstruction. The improved algorithms have been developed into a software
      package which can be obtained via the world wide web at
      http://ncmi.bioch.bcm.tmc.edu/pthuman.

PMID- 9262024
TI  - The use of anisotropic data in 125I prostate implants.
AB  - The report recently published by AAPM Task Group 43' (TG43) recommends the use of
      a two dimensional dose distribution function for the dosimetry associated with
      125I, 192Ir and 103Pd sources. For commercial planning systems that cannot be
      readily adapted to use a two dimensional function, a point source approximation
      is provided. The dose distribution around an array of 125I seeds has been
      calculated using the two dimensional model and the point source approximation.
      Isodose distributions through selected planes and dose volume histograms of
      selected cubic volumes show that differences between the two models for this
      array are insignificant, particularly in view of the uncertainties associated
      with using the data which is provided by TG43 for the two dimensional anisotropy
      function.

PMID- 9262025
TI  - A reference air kerma rate calibration protocol for a 370 GBq 192Ir high dose
      rate brachytherapy source.
AB  - A suggested protocol for the in-air calibration of 192Ir High Dose Rate (HDR)
      Brachytherapy sources is presented. The protocol was constructed using Nucletron
      Oldelft HDR brachytherapy equipment and should be transportable to any High Dose
      Rate Brachytherapy Afterloader system.

PMID- 9262026
TI  - Comparative evaluation of Wellhofer ion chamber array and Scanditronix diode
      array for dynamic wedge dosimetry.
AB  - Normalised profiles have been measured using the Scanditronix diode array and the
      Wellhofer ion chamber array for the Varian dynamic wedge. Agreement was of the
      order of 0.1% of central axis peak dose for an open beam at depth, 0.3% for a
      dynamic wedge field at depth, and up to 0.6% at the peak depth. The use of the
      arrays for data acquisition is discussed, including user interface limitations.
      Data reproducibility is determined to be of the order of 0.1% for both systems.
      The issue of beam hardening within dynamic wedges is discussed and resolved in
      terms of the dose-gradient effect. A method for interpolation between dynamic
      wedge profiles using open beam data is presented that allows construction of
      isodoses to an estimated accuracy of 0.7%. Finally a benchmark for comparison of
      different measuring systems based on quality assurance requirements for the
      enhanced dynamic wedge is suggested.

PMID- 9262027
TI  - A Monte Carlo model for bone mineral measurement using dual energy X-ray
      absorptiometry.
AB  - A detailed Monte Carlo model designed to simulate bone mineral measurements using
      a typical K-edge DEXA technique (LUNAR DPX-L bone densitometer) has been
      developed. Factors considered in the model include measurement geometry, K-edge
      filtration of the X-ray spectrum, photon statistics, count rate corrections and
      detector resolution. Two semi infinite elliptical phantoms simulating the lumbar
      spine and the femoral neck respectively have been used. Each phantom consists of
      four tissue components-fat, lean soft tissue, cortical bone and trabecular bone.
      Model results display similar levels of accuracy and precision to those observed
      in clinical practice. The Monte Carlo model of bone mineral measurements provides
      a valid tool for study of the LUNAR DPX-L DEXA technique.

PMID- 9262028
TI  - Patient doses from chest radiography in Victoria.
AB  - This survey examines doses from PA chest radiography at radiology practices,
      private hospitals and public hospitals throughout metropolitan and country
      Victoria. Data were collected from 111 individual X-ray units at 86 different
      practices. Entrance skin doses in air were measured for exposure factors used by
      the centre for a 23 cm thick male chest. A CDRH LucA1 chest phantom was used when
      making these measurements. About half of the centres used grid technique and half
      used non-grid technique. There was a factor of greater than 10 difference in the
      entrance dose delivered between the highest dose centre and the lowest dose
      centre for non-grid centres; and a factor of about 5 for centres using grids.
      Factors contributing to the high doses recorded at some centres were identified.
      Guidance levels for chest radiography based on the third quartile value of the
      entrance doses from this survey have been recommended and compared with guidance
      levels recommended in other countries.

PMID- 9262029
TI  - X-ray intensifying screen visible light detection meter.
AB  - A light meter has been designed and built for the purpose of measuring the light
      emitted from an intensifying screen during x-ray irradiation. The meter uses a
      photodiode detector with a minimal drift amplification system. The meter
      repeatability was better than 0.5% and was found to be linear. A significant x
      ray induced signal was recorded during measurement which needed to be subtracted
      from readings to deduce the intensification screen light output. The energy
      response of four screen types was subsequently measured.

PMID- 9262030
TI  - Skin dose reduction by a clinically viable magnetic deflector.
AB  - A variable magnetic deflector which attaches onto the treatment head of a linear
      accelerator has reduced skin dose by as much as 65% for 6MV x-rays. The magnetic
      deflector is constructed from Neodymium Iron Boron (NdFeB) rare earth magnets. It
      weighs approximately 15 kg and is designed to easily fit onto the accessory mount
      of a clinical linear accelerator. All field sizes are attainable up to 35 cm x 35
      cm at 100 cm SSD. The gap between the magnetic poles can be adjusted, providing
      the highest field strength for each field size. Magnetic field strengths up to
      0.55 Tesla are attainable. For a 6MV x-ray beam with a 10 mm perspex block tray,
      surface dose is reduced from 29% to 14% and from 59% to 37% for a 20 cm x 20 cm
      and 35 cm x 35 cm field size, respectively. Results at varying SSD's have shown
      at least 10 cm of space must be allowed between the magnets and patient for
      adequate reduction of skin dose through removal of electron contaminants.

PMID- 9262031
TI  - Acceptance testing, commissioning and quality assurance for a 370 GBq 192Ir HDR
      brachytherapy afterloader.
AB  - Proposed methods for the initial source installation tests, acceptance testing
      and a continuing quality assurance program are presented for a Nucletron-Odelft
      High Dose-Rate Brachytherapy Afterloader system.

PMID- 9262032
TI  - The calibration of plane parallel ionisation chambers for the measurement of
      absorbed dose in electron beams of low to medium energies. Part 2: The PTW/MARKUS
      chamber.
AB  - The purpose of Part 2 study of calibration methods for plane parallel ionisation
      chambers was to determine the feasibility of using beams of calibration of the
      MARKUS chamber other than the standard AAPM TG39 reference beams of 60Co and a
      high energy electron beam (E0 > or = 15 MeV). A previous study of the NACP
      chamber had demonstrated an acceptable level of accuracy with corresponding
      spread of -0.5% to +0.8% for its calibration in non-standard situations (medium
      to low energy electron and photon beams). For non-standard situations the spread
      in NDMARKUS values was found to be +/-2.5%. The results suggest that user
      calibrations of the MARKUS chamber in non-standard situations are associated with
      more uncertainties than is the case with the NACP chamber.

PMID- 9262034
TI  - Surveillance of viral infections in donated blood.

PMID- 9262033
TI  - Chart recorder paper minder.
AB  - Many paper based chart recorders still suffer from paper uptake systems for the
      collection of chart record that operate inefficiently or haphazardly. An
      efficient low cost paper minder using 1.2 mm diameter stainless steel wire for
      the Siemens-Elema AB Mingograph 7, has been developed. This wire pivots from the
      end of the chart viewing table and provides an effective force to redirect paper
      into the standard collecting basket over the entire range of paper speeds.

PMID- 9262035
TI  - Comparison of a once-a-day sustained-release morphine formulation with standard
      oral morphine treatment for cancer pain.
AB  - Kadian/Kapanol (K) is a capsule formulation of morphine designed for 12- or 24
      hourly dosing. This double-blind study compared the efficacy and safety of K
      every 24 hr to K every 12 hr and MS Contin tablets (MSC) every 12 hr. One hundred
      fifty-two patients with cancer pain were titrated to adequate analgesia with
      immediate-release morphine (IRM) solution. Stabilized patients were randonized to
      one of the three treatments for 7 +/- 1 days. Rescue medication was IRM tablets.
      Efficacy and safety were assessed by time to first remedication and total dose of
      rescue medication, pain scores, global assessments, and incidence of morphine
      related side effects. Fifty-four patients were treated with K every 24 hr. 45
      with K every 12 hr. and 53 with MSC every 12 hr. Mean age was 61 years and mean
      total daily dose of morphine was 138 mg. Forty-six percent of the K every 24 hr
      patients, 51% of the K every 12 hr patients, and 55% of the MSC every 12 hr
      patients required rescue medication on the final day. Time to remedication was
      16.0 hr for K every 24 hr, 9.1 hr for K every 12 hr and 8.7 hr for MSC every 12
      hr (P = 0.0010). Patient global assessment significantly favored K every 24 hr
      over MSC every 12 hr (P = 0.018). There were no statistically significant
      differences among the treatments for any morphine-related side effects when
      adjusted for baseline. K had efficacy and safety profiles similar to MSC every 12
      hr but had the advantage of 12- or 24-hourly administration.

PMID- 9262036
TI  - Cancer pain education among family physicians.
AB  - This study used performance-based testing (objective structured clinical
      evaluation, OSCE) to evaluate the skills of family physicians in assessing and
      managing the severe pain of a cancer patient, and evaluated a new method of
      education about the management of cancer pain. Twenty-four primary care
      physicians completed a detailed pain assessment of the same standardized cancer
      pain patient (Part A). A proctor observed the interviews and rated the physicians
      on a variety of pre-determined items believed to be important for pain
      assessment. The physicians were then allowed 5 min to answer management questions
      about the patient's cancer pain (Part B). After reviewing each physician's
      performance on Parts A and B, the proctor provided immediate feedback and
      instruction (Part C) on basic principles of cancer pain assessment and
      management. On average, the primary care physicians asked 52% (+/-4.5%) of the
      indicated questions of a detailed pain assessment. Performance was poorest in
      asking about previous pain history, temporal pattern of pain, and pain intensity.
      Performance on the pain assessment was best for eliciting pain location and pain
      relieving factors. Primary care physicians obtained mean scores of 36% (+/-3%) on
      Part B of the OSCE. Although opioid therapy was frequently prescribed, only 42%
      of prescriptions were for regular administration. Performance on Parts A and B
      correlated poorly with years in practice, and older physicians tended to perform
      a less detailed pain assessment than their younger colleagues. Most physicians
      enjoyed participating in this instructional formal and believed that the proctor
      feedback increased the educational value of the module. The results of our study
      suggest that many family physicians may be inadequate in their clinical
      assessment and management of cancer pain. Our study supports the need for
      continuing education in cancer pain management, regardless of years in practice.
      Further study should evaluate the effects of different educational programs on
      clinical practice in patient care.

PMID- 9262037
TI  - A double-blind, placebo-controlled, randomized trial to evaluate the role of
      tetrachlorodecaoxide in the management of chemotherapy-induced oral mucositis.
AB  - We conducted a double-blind, placebo-controlled, randomized trial to evaluate the
      efficacy and safety of tetrachlorodecaoxide (TCDO) in patients with chemotherapy
      induced mucositis. Sixty-two patients with World Health Organization grade II-IV
      oral mucositis were eligible for the study. They were randomized to receive TCDO
      or placebo, 10 ml, twice daily, swish and swallow, for 7 days. Patients were
      evaluated for oral pain, dysphagia, and oral intake. Downgrading and total
      duration of mucositis were documented. Thirty-two were randomized to receive
      TCDO. Thirty received the placebo. All were evaluable. Both arms were well
      matched for age, gender, type of underlying neoplasm, and prior history of oral
      mucositis. Intensity of initial symptoms, degree of mucositis, and time period
      between delivery of chemotherapy and development of mucositis were also similar.
      Post-therapy evaluation revealed no significant difference in the mean grade of
      oral and esophageal pain, or dysphagia between TCDO and placebo. Downgrading or
      total duration of mucositis did not differ between the two groups. Oral intake
      improved significantly in patients taking TCDO. Time to subjective improvement in
      oral pain was significantly shorter with TCDO (3.1 versus 3.6 days). Evaluation
      on day 3 revealed that 77% of those receiving TCDO were free of oral pain in
      comparison to 46% receiving placebo (P = 0.05). These results indicate that TCDO
      may be helpful in palliating some of the symptoms related to oral mucositis. The
      therapeutic benefit, however, is small and needs to be confirmed in a larger
      trial.

PMID- 9262038
TI  - Chronic pain is a manifestation of the Ehlers-Danlos syndrome.
AB  - The Ehlers-Danlos syndrome (EDS) is a group of heritable systemic disorders of
      connective tissue manifesting joint hypermobility, skin extensibility, and tissue
      fragility. Although the presence of pain has been documented in the various types
      of the EDS, its natural history, distribution, and management have not been
      defined. We conducted a structured interview in 51 individuals affected with
      different types of EDS. Affected individuals reported chronic pain of early onset
      involving most frequently the shoulders, hands, and knees. Pain was generally
      refractory to a variety of pharmacologic and physical interventions. Chronic pain
      is a common manifestation of EDS.

PMID- 9262039
TI  - Dying cancer patients: choices at the end of life.
AB  - Physician-assisted suicide and euthanasia have recently received considerable
      attention in the literature and in the courts. Surveys have been conducted
      assessing physicians' attitudes toward euthanasia and physician-assisted suicide.
      Five patients were followed and counseled in a cancer support group from time of
      diagnosis of their malignancies until death. These case reports demonstrate the
      need for further studies to include interviews of dying patients. Review of these
      cases indicates that factors in addition to pain management and the treatment of
      depression, such as care by family members, support groups, and spiritual
      concerns, can influence patients not to act on their previous requests for
      euthanasia or physician-assisted suicide.

PMID- 9262040
TI  - Neuropathic pain in cancer patients: mechanisms, syndromes, and clinical
      controversies.
AB  - The identification of a neuropathic pain syndrome in a cancer patient requires a
      focused clinical evaluation based on knowledge of common neuropathic pain
      syndromes. If a tumor is directly involved in the etiology of the pain, oncologic
      treatment is an initial consideration and may include surgery, radiation, or
      chemotherapy. There is no single accepted algorithm for the analgesic treatment
      of neuropathic pain and a systematic approach utilizing therapeutic trials of
      specific agents at gradually increasing doses is warranted. A trial of opioids,
      perhaps in combination with an NSAID, is warranted. If the pain is relatively
      unresponsive to an opioid, a trial with an adjuvant analgesic is reasonable. For
      example, a tricyclic antidepressant might be selected early for patients with
      continuous dysesthesia, and early treatment with an anticonvulsant might be used
      if the pain is predominantly lancinating or paroxysmal. Other adjuvant analgesics
      can be selected if there is insufficient response to these agents. A trial of
      sympathetic blockade, pharmacologic, anesthetic or surgical, should be considered
      in patients with evidence of causalgia or reflex sympathetic dystrophy.
      Physiatric modalities such as massage, heat, or cold; counterstimulation or
      transcutaneous electrical nerve stimulation (TENS), and orthopedic interventions,
      such as braces and splints may be useful. Epidural injections or neurostimulation
      of the spinal cord or brain can be considered in selected cases where appropriate
      expertise is available. Treatment of neuropathic pain remains a challenge for
      both clinicians and patients. The complexity of syndromes and underlying
      etiologic mechanisms warrants further clinical trials to determine the best
      treatment modalities for individual pain syndromes.

PMID- 9262041
TI  - Seizure after withdrawal from supratherapeutic doses of zolpidem tartrate, a
      selective omega I benzodiazepine receptor agonist.

PMID- 9262042
TI  - Successful management of multiple enterocutaneous fistulas in a patient with
      metastatic colon cancer.
AB  - Enterocutaneous fistula development is not uncommon in patients with advanced
      cancer and can be very challenging to manage. The authors present a case study of
      a patient with multiple enterocutaneous fistulas that developed in the setting of
      metastatic colon cancer. Assessment methods and interventions that permitted
      successful management are discussed with emphasis on the value of
      multidisciplinary care.

PMID- 9262043
TI  - Quality of life rediscovered: implications for clinical outcome and health
      economics in schizophrenia.

PMID- 9262044
TI  - Psychopathology and quality of life in schizophrenia.
AB  - This study was conducted to evaluate the relationship between psychopathology and
      quality of life in individuals with schizophrenia. The findings indicate that
      psychopathology, as determined by total Brief Psychiatric Rating Scale (BPRS)
      score, correlates negatively with global life satisfaction and subjective quality
      of life subscales, but not with objective ones. When positive and negative
      symptom clusters were examined, negative symptoms appeared to have a greater
      impact on subjective measures of quality of life.

PMID- 9262045
TI  - The influence of neurocognitive deficits and symptoms on quality of life in
      schizophrenia.
AB  - The purpose of the present study was to examine the relationship between
      neurocognitive deficits and self-reported quality of life in order to examine
      whether neurocognitive impairment interferes with any aspects of quality of life
      for patients with schizophrenia. Forty-two outpatients with stable chronic
      schizophrenia were assessed for neurocognitive deficits using a computerized test
      battery, and all patients completed a version of the Sickness Impact Profile
      (SIP) to assess their quality of life across a variety of domains. The
      neurocognitive assessment tests revealed significant deficits compared with
      normal control subjects, particularly with respect to impaired iconic memory and
      frontal functioning. Patients reported that their quality of life was
      compromised. Despite the substantiation of marked neurocognitive deficits and
      reduced quality of life, correlations between neurocognitive deficits and quality
      of life were largely nonsignificant or very weak. Symptom expression, however,
      particularly with regard to general psychopathology on the Positive and Negative
      Syndrome Scale (PANSS), was significantly associated with quality of life. These
      results suggest that neurocognitive deficits in schizophrenia, while often
      profound, appear to have little direct impact on the patient's perceived quality
      of life.

PMID- 9262046
TI  - Quality of life and response of negative symptoms in schizophrenia to haloperidol
      and the atypical antipsychotic remoxipride. The Canadian Remoxipride Group.
AB  - In a large, multicenter, double-blind study of the effect of haloperidol and the
      atypical antipsychotic remoxipride on improvement of negative symptoms in
      schizophrenia, quality of life was also assessed using a modified version of the
      Sickness Impact Profile (SIP). Compared with previous studies, this study had a
      longer duration (28 weeks), and the dose of the comparator, haloperidol, was much
      lower. At the end of the study, compared with the baseline, both treatment groups
      reported comparable improvement in negative symptoms as defined by the protocol
      (at least 20% improvement). Similarly, both groups showed comparable changes on
      global and multidimensional self-assessments of quality of life. All the
      subfactors of the modified version of the SIP were similar in both groups, except
      for the subfactor that relates to alertness behavior, which possibly reflects
      remoxipride's lack of any sedating properties compared with haloperidol. This
      study presents an approach for inclusion of quality of life as an outcome measure
      in the design of clinical trials of new antipsychotic medications.

PMID- 9262047
TI  - Quality of life and social integration of severely mentally ill patients: a
      longitudinal study.
AB  - The quality of life concept serves to measure functional changes and program
      outcome. Patients with schizophrenia have an improved prognosis. Is quality of
      life improving over time, and if so, over what period? These questions were
      addressed in a longitudinal study where subjective quality of life (SQOL) was
      rated by severely mentally ill patients living in the community and using support
      services located in an outlying area of Quebec. The Satisfaction for Life Domains
      Scale (SLDS) (Baker and Intagliata 1982) measuring SQOL as a whole and in
      specific domains (for example, housing, finances, social relationships) was
      repeated over a period of 7 y. Results show that SQOL ratings received the same
      scores after 7 y. Functional status was decreased, while social integration
      improved and more services were used. The results could be due to sample
      characteristics or to the ambiguity of the SQOL construct. In our opinion,
      extensive community-based support services may have played a key role in the
      maintenance of patient's quality of life.

PMID- 9262048
TI  - Methods of pharmacoeconomic evaluation of psychopharmacologic therapies for
      patients with schizophrenia.
AB  - The pharmacoeconomic evaluation of psychopharmacologic treatments for patients
      with schizophrenia requires attention to the clinical and quality of life effects
      of the therapy, as well as its impact on the use and cost of medical services.
      The results of pharmacoeconomic studies help clinicians and health care decision
      makers determine treatments that provide the most benefit to patient functioning
      and well-being at the most acceptable medical cost. Various research designs and
      methods have been used to evaluate the cost-effectiveness of antipsychotic drugs,
      including retrospective studies, prospective studies, and clinical decision
      analysis models. This article summarizes these research designs and their
      strengths and weaknesses in the evaluation of antipsychotic drugs for treating
      schizophrenia.

PMID- 9262049
TI  - Quality of life measurement during antipsychotic drug therapy of schizophrenia.
AB  - The strategy for measuring quality of life and the choice of a rating scale
      should follow a rational scheme aimed at capturing the key components of quality
      of life of a specified clinical population. This is achieved through defining the
      purpose of the study, identifying the clinical population and its needs,
      developing a situation-specific quality of life model, and choosing a battery of
      psychometrically sound and user-friendly rating scales based on the model.
      Patients' self-reports and subjective feelings should be central to quality of
      life measurement, which should also monitor symptom severity, drug side effects,
      and psychosocial adjustment. This article describes the application of these
      principles in the context of antipsychotic drug therapy of schizophrenia and
      identifies potential problems that may arise from the conceptual, psychometric,
      clinical, and other feasibility issues. The highly subjective nature of the
      disorder, together with the poor insight, lack of motivation, and neurocognitive
      deficits of those who are afflicted, poses special difficulties for obtaining and
      interpreting patients' quality of life appraisals in schizophrenia.

PMID- 9262050
TI  - Venlafaxine-fluoxetine-nortriptyline interaction.

PMID- 9262051
TI  - Deoxyribonuclease I and its clinical applications.
AB  - DNases are DNA hydrolyzing enzymes. The well-characterized bovine pancreatic
      DNase I, the first DNase discovered, is a model DNase for studying the structure
      function relationships of the DNase I type enzymes. The Epstein-Barr virus
      produces a DNase with an unknown biologic function other than degrading DNA, and
      this viral DNase has been used as an Epstein-Barr viral marker. Human DNase I
      exhibits polymorphism that can be used for forensic identification and for
      correlation with certain diseases. Variations in serum DNase activities have been
      implicated as the result of disease states and measurements of DNase activities
      are often used for diagnosis and prognosis. Recombinant human DNase I has been
      administered in cystic fibrosis patients to improve mucociliary clearance and
      pulmonary function. Thus, although the primary function of DNase is to degrade
      DNA, there are many reports of its clinical applications.

PMID- 9262052
TI  - Neuropathology of amyotrophic lateral sclerosis: new perspectives on an old
      disease.
AB  - Recent discoveries on linkage of the gene mutation of an enzyme, copper/zinc
      superoxide dismutase 1 (SOD-1), to familial amyotrophic lateral sclerosis (ALS)
      (which constitutes about 1% of all ALS cases) and several transgenic mouse models
      of ALS have shed light on potential pathogenetic processes involved in this
      disease. Any speculation as to the pathogenesis of ALS must reflect the unique
      neurobiology of motor neurons. The most distinctive aspects of motor neurons are
      their asymmetry, large size, and enormously elongated and thick axons. These
      characteristics also contribute to their vulnerability to ALS. The determinants
      of these unique properties are the intermediate cytoskeletal filaments, and the
      neurofilaments of motor neurons. This characteristic is not exclusive to motor
      neurons and is shared with other neurons with long axons, including some sensory
      neurons that are also involved in ALS. The histopathology of the early stages of
      ALS overwhelmingly suggests that accumulation and aggregation of neurofilaments
      within motor neurons is intimately related to the morphogenesis of the unique
      cytoplasmic inclusions, and plays a central role in the pathogenesis of the
      disease. Understanding of the causal relationship and the morphogenesis of
      inclusion bodies is critical in any attempt to reverse this complex disease
      process, which potentially involves the neurotoxic effects of free radicals
      (nitric oxide, superoxide, hydrogen peroxide, and peroxynitrite, etc) on
      neurofilaments. By emphasizing the unique make-up of motor neurons, this review
      intends to reevaluate and reinterpret the basic neuropathology of ALS in the
      light of recent molecular genetic-data.

PMID- 9262053
TI  - Apolipoprotein B gene polymorphisms in Taiwanese ischemic stroke patients.
AB  - We analyzed the AluI restriction fragment length polymorphism (RFLP) of the
      apolipoprotein B (apoB) gene to determine the association between AluI allelic
      distribution and the occurrence of ischemic stroke in Taiwan. A total of 44
      healthy volunteers and 159 ischemic stroke patients were included in the study.
      The allele frequency of AluI was very similar in the two groups, 0.87 in the
      patient group and 0.89 in the control group, for the major allele A-. The
      distribution of A-/A-, A-/A+, and A+/A+ genotypes of the patients was not
      significantly different from that of the controls. Among ischemic stroke
      patients, the A+ allele of the AluI restriction site was significantly associated
      with elevated apoB levels. The results of this study suggest that the presence of
      the rare AluI RFLP may contribute to an elevated plasma apoB level, which is a
      known risk factor for ischemic stroke.

PMID- 9262054
TI  - Characterization of Ca(2+)- and voltage-dependent nonselective cation channels in
      human HepG2 cells.
AB  - Nonselective cation channels have been identified and linked to important cell
      functions in rat hepatocytes. In this study, we characterized inward rectifying
      nonselective cation channels in detail by the patch clamp technique in human
      HepG2 cells. Channel properties were studied with high resistance borosilicate
      pipettes in cell-attached and inside-out configurations. With Ringer's solution
      and KCl as pipette solutions, the conductances were 19.7 +/- 2.1 and 22.2 +/- 0.0
      picosiemens (pS), and reversal potentials were 30.9 +/- 3.5 and 31.3 +/- 4.6 mV,
      respectively. The channel was permeable to Ba2+, and the sequence of permeability
      ratios was Na+ > K+ > Cs+ > Ba2+. In the cell-attached configuration, the channel
      had a higher opening probability at depolarizing potential than at
      hyperpolarizing. In the inside-out patches with symmetric Ringer's solution, the
      current voltage curve was linear with conductance of 19.8 +/- 0.9 pS. Reversal
      potential shifted from -0.2 +/- 1.0 mV to 23.2 +/- 1.0 mV when the bath solution
      was replaced by dilute Ringer's solution. In the inside-out configuration, the
      gating was Ca(2+)-dependent, and the opening probability increased with
      increasing intracellular calcium concentration ([Ca2+]i). An outward rectifying
      channel appeared when [Ca2+]i was less than 1 mumol/L. The nonselective channel
      was reversibly blocked by 10 mumol/L internal flufenamic acid. We conclude that
      Ca(2+)- and voltage-dependent nonselective cation channels are present in human
      HepG2 cells. The channels might be involved in the regulation of Ca2+ influx and
      are associated with activation of other ion channels.

PMID- 9262055
TI  - Genomic cloning and sequence analysis of Taiwan-3 human polyomavirus JC virus.
AB  - Four different-strains of human polyomavirus JC virus (JCV), CY, Taiwan-1, Taiwan
      2, and Taiwan-3, have been found in pregnant women and autoimmune disease
      patients in Taiwan. In this study, we report the cloning and sequencing of the
      Taiwan-3 JCV, virus isolated from the urine of an immunosuppressed patient with
      rheumatoid arthritis. The viral genome was amplified by polymerase chain reaction
      and then cloned into a prokaryotic replicative plasmid, pGEM-7Zf(-). The genomic
      DNA was sequenced and found to comprise 5,111 base pairs. The enhancer-promoter
      region of the viral genome lacks a copy of pentanucleotide-A (GGGAA) and
      pentanucleotide-B (AAAGC) compared to the CY archetypal JCV. There are 108
      nucleotides altered in the total genome, excluding the variable part of the
      enhancer-promoter region, between Mad-1 (the prototype JC virus) and Taiwan-3.
      The enhancer-promoter region has approximately 25% of the altered nucleotides,
      resulting in amino acid changes in the open reading frames for I.T. capsid
      proteins (VP1, VP2, and VP3), and the agno protein. The cloned Taiwan-3, genome
      will provide an source for physiologic and pathologic investigation of the JCV
      virus in the future.

PMID- 9262056
TI  - Molecular cloning and expression of a fungal immunomodulatory protein, FIP-fve,
      from Flammulina velutipes.
AB  - FIP-fve, a fungal immunomodulatory protein, was isolated from the fruiting bodies
      of the edible mushroom, Flammulina velutipes. FIP-fve was shown to stimulate
      blast-forming activity of human peripheral blood lymphocytes and gene expression
      of interleukin-2, interferon-gamma and tumor necrosis factor-alpha. Repeated
      administration of FIP-fve to mice inhibits the Arthur and systemic anaphylaxis
      reactions. FIP-fve cDNA was cloned and sequenced, and the amino acid sequence of
      FIP-fve deduced from the nucleotide sequence is identical to that previously
      determined by protein sequencing. FIP-fve cDNA was amplified by polymerase chain
      reaction, ligated into the expression vector, pGEX-2T, and expressed in
      Escherichia coli as a fusion protein of glutathione S-transferase (GST) and FIP
      fve. The GST-FIP-fve fusion protein was soluble, and the yield of recombinant FIP
      fve was about 5 mg/L of induced culture. The recombinant FIP-fve was obtained by
      cleaving the GST-FIP-fve fusion protein with thrombin and purifing to
      homogeneity. The recombinant FIP-fve had about 50% of the immunomodulatory
      activity of the native FIP-fve.

PMID- 9262057
TI  - Factors associated with the therapeutic efficacy of retinoic acids on malignant
      lymphomas.
AB  - We recently reported the successful use of retinoic acids in the treatment of
      refractory lymphoma. The biologic determinants predicting response of lymphomas
      to retinoic acid remain unknown. This study was conducted to explore this
      question using in vitro models. Sensitivity of representative lymphoma cells to
      13-cis-retinoic acid was determined. Sensitive and resistant cell lines were then
      compared for their baseline and/or retinoic-acid-regulated expression of total
      cellular retinoic acid binding protein, retinoic acid receptor (RAR)-alpha, RAR
      beta, RAR-gamma mRNA, retinoid X receptor (RXR)-alpha, RXR-beta, RXR-gamma mRNA,
      transforming growth factor (TGF)-beta 1 and TGF-beta 1 receptors, and Fas (Apo-I)
      mRNA. The results showed that four of five T, two of three Hodgkin's, and none of
      six B cell lymphoma cell lines were sensitive (IC30 < 1.5 mmol/L) to 13-cis
      retinoic acid. Further analyses revealed several of the above-mentioned
      parameters may be relevant to retinoic acid sensitivity. Baseline expression of
      TGF-beta 1 receptors was present in all of the five sensitive cell lines
      examined, but in only one of the four resistant cell lines. The correlation of
      Fas expression and retinoic acid sensitivity was good for B cell lines, but not
      apparent for T cell or Hodgkin's cell lines. On exposure to retinoic acid, an
      immediate and prolonged upregulation of RAR-alpha mRNA expression, lasting for
      more than 12 hours, occurred in all sensitive cell lines, but only minimal or
      transient induction was seen in resistant cells. Together, these data suggested
      that; 1) retinoic acid has a preferential effect on T cell and Hodgkin's lymphoma
      cell lines; 2) autoregulation of RAR-alpha by retinoic acids, and the presence of
      TGF-beta 1 receptors may be relevant to the response of lymphomas to treatment
      with retinoic acids.

PMID- 9262058
TI  - Factors affecting specialty and location of practice of government-sponsored
      physicians in Taiwan.
AB  - Geographic and specialty maldistribution have created problems of physician
      supply in Taiwan. Previous small-scale government-sponsored physician (GSP)
      programs in Taiwan have had only limited effects. To solve this problem, the
      National Yang-Ming Medical College was established in 1975; it supplied its first
      government-sponsored physician graduates in 1982. Obligatory service in different
      specialties and geographic areas were assigned to graduates according to their
      personal preference and school performance. In this study, we evaluated the
      factors affecting the choice of specialty and location for these GSPs during the
      6-year obligatory service period. Data on Department of Health-regulated GSPs who
      finished obligatory service prior to 1991 were obtained from the GSP files,
      medical student files, and the National Medical Manpower Information System for
      the years 1982 to 1985. Logistic regression was used to assess the effect of year
      of entry, age, gender, rank in class, and hometown of the GSPs on specialty
      choice upon entry into the obligatory service period. Both logistic regression
      and generalized estimating equations were used to analyze the effects of these
      parameters and location experiences during obligatory service on location
      selection after the obligatory service period. We found that rural experience
      during obligatory service was strongly associated with the choice of rural
      practice after the completion of the obligatory service. Male gender, a later
      year of entry to the program, and having a rural hometown were only moderately
      associated with the choice of rural practice. A more comprehensive evaluation and
      review of the effect of the GSP program on overall specialty and location
      distribution of physicians is needed to provide guidelines for improvement of
      current GSP program policies.

PMID- 9262059
TI  - Prenatal molecular diagnosis of RET proto-oncogene mutation in multiple endocrine
      neoplasia type 2A.
AB  - We report a case of multiple endocrine neoplasia type 2A (MEN 2A) diagnosed
      prenatally at 16 weeks gestation. The 35-year-old mother is a MEN 2A patient. She
      had had three prior pregnancies: one resulted in a stillbirth; one produced a
      genetically unaffected boy; and the third was terminated in the first trimester
      owing to a diagnosis of blighted ovum. Autopsy did not reveal the cause of death
      of the stillborn infant, who was also found to be affected with MEN 2A by
      molecular study of paraffin-embedded tissue. Because of poor obstetric history
      and the patient's age, amniocentesis for cytogenetic and molecular studies was
      performed at 16 weeks' gestation during the pregnancy under discussion. As with
      other affected members in the mother's family, the missense mutation of TGC to
      TTC at codon 634 of the RET proto-oncogene was found in amniotic fluid cells.
      Analysis of DNA extracted from the lymphocytes of the infant's blood at birth
      confirmed the diagnosis. To our knowledge, this is the first report of prenatal
      diagnosis of MEN 2A.

PMID- 9262060
TI  - Adenocarcinoma combined with malignant peripheral nerve sheath tumor of the
      gallbladder.
AB  - Adenocarcinoma of the gallbladder combined with a malignant peripheral nerve
      sheath tumor (MPNST) in the gallbladder in an 81-year-old woman is reported. The
      resected gallbladder showed two distinct tumor components, the epithelioid type
      of MPNST and adenocarcinoma with areas of mucin production. Although the
      immediate postoperative course was uneventful, a pathologic fracture of her right
      upper femur developed 4 months after the cholecystectomy. The pathology was
      determined to be a feature of metastatic MPNST rather than of adenocarcinoma. A
      whole body bone scan revealed multiple metastases, including the left parietal
      skull, left ninth rib, seventh thoracic vertebra, and right upper third of the
      femur. Despite cholecystectomy and postoperative irradiation therapy, she died 6
      months after diagnosis of the tumor. Without an autopsy the primary site of the
      MPNST was unknown. We found that the prognosis was very poor in patients with
      distal metastatic MPNST, especially in older patients.

PMID- 9262061
TI  - Slipped capital femoral epiphyses in a patient with primary hyperparathyroidism.
AB  - Slipped capital femoral epiphyses are rarely associated with primary
      hyperparathyroidism, and only four cases have been documented in the English
      literature. We report such a case. A 13-year-old boy presented with bilateral
      slipped capital femoral epiphyses. Investigation showed that he had primary
      hyperparathyroidism due to a parathyroid adenoma. The adenoma was removed, and
      then the epiphyses were pinned in situ 3 weeks later. The pins were removed 3
      months postoperatively when the physes had closed. The patient had a painless hip
      1 year later at follow-up. We concluded that identification and excision of the
      hyperparathyroid adenoma and in situ pinning of the slipped epiphyses results in
      satisfactory treatment of the condition.

PMID- 9262062
TI  - Treatment of a large segmental bone defect with allograft and autogenous bone
      marrow graft.
AB  - Management of segmental bone defects is a challenge to orthopedic surgeons. We
      report a 23-year-old man who sustained segmental bone loss of 9 cm in length in
      his left femur due to an open fracture. Open reduction and internal fixation with
      a 95 degrees angle blade plate and screws, supplemented with a composite of two
      femoral head allografts and a graft of 100 mL of autogenous bone marrow, was
      performed 3 weeks after the injury, when the soft tissues had healed. The
      postoperative rehabilitation program included delayed weight bearing (crutches
      for 3 months), a limited early range of motion of the left knee, and quadriceps
      muscle exercise. Callus bridging was noted on x-ray films 3 months
      postoperatively. Clinical and radiographic union were noted 6 months after the
      surgery. We suggest that this new and simple method can be applied to
      successfully treat segmental bone loss of more than 6 cm in length.

PMID- 9262063
TI  - Bacteremia caused by Helicobacter cinaedi in an AIDS patients.
AB  - Helicobacter cinaedi bacteremia has been infrequently described in homosexual
      patients with HIV infection. It may recur despite appropriate antimicrobial
      therapy. We report a bisexual patient with AIDS in whom H. cinaedi bacteremia
      developed and presented with prolonged fever and chronic diarrhea. The symptoms
      resolved without relapse after intravenous immunoglobulin therapy, which was
      administered for the treatment of concurrent parvovirus B19-associated anemia,
      and subsequent treatment with clarithromycin for 14 days.

PMID- 9262064
TI  - Primary cervical neuroblastoma in infants.
AB  - Although neuroblastoma is a relatively common malignancy of childhood, it is
      rarely of cervical origin. We encountered two cases of primary cervical
      neuroblastoma in infants. The first case was in a newborn who presented with
      noisy breathing, dyspnea, and choking on feeding soon after birth. Physical
      examination disclosed a left retropharyngeal mass near the midline causing
      aerodigestive compromise. Magnetic resonance imaging showed a well-defined
      hyperintense mass in the corresponding region. The infant underwent complete
      surgical excision of the mass 1 month after birth. The pathology report confirmed
      neuroblastoma. Horner's syndrome developed soon after surgery but resolved
      spontaneously within 6 months. No recurrence was noted during a 3-year follow-up
      period. The second patient, a 5-month-old female, presented with stridor and
      shortness of breath of 2-weeks' duration due to a right cervical mass. Magnetic
      resonance imaging showed a parapharyngeal mass suggestive of neuroblastoma.
      Complete surgical excision was done at the expense of sacrificing the sympathetic
      nerve trunk. The pathologic diagnosis was moderately differentiated
      neuroblastoma. No recurrence was noted when the patient was seen 2 years after
      surgery, although right-sided Horner's syndrome persisted. Surgical intervention
      can result in a good prognosis for low stage cervical neuroblastomas; however,
      long-term follow-up is important.

PMID- 9262065
TI  - Standards for services for people with severe mental illness.

PMID- 9262066
TI  - The Program of Assertive Community Treatment (PACT): the model and its
      replication.
AB  - The Program of Assertive Community Treatment (PACT) has been investigated in
      Madison and at other replication sites, and the positive results for clients have
      led to more widespread dissemination of the PACT model. This chapter presents a
      basic introduction to the model of care, research findings, and views on PACT
      model replication.

PMID- 9262067
TI  - Becoming real: from model programs to implemented services.

PMID- 9262068
TI  - A model of the dissemination of self-help in public mental health systems.
AB  - Self-help in public mental health systems has been disseminated with five
      different strategies; these strategies sometimes overlap and complement one
      another. The four forms of self-help discussed are mutual support, advocacy,
      consumer/survivor-run services, and coping.

PMID- 9262069
TI  - Stages in realizing the international diffusion of a single way of working: the
      clubhouse model.
AB  - From modest beginnings, Fountain House has assisted the spread of the clubhouse
      philosophy across the United States, and more recently the clubhouse movement has
      spread internationally. At the same time that dissemination of the innovative
      clubhouse approach has taken place, there has been careful specification of the
      contents of the clubhouse approach.

PMID- 9262070
TI  - Employment for people with psychiatric disabilities: knowledge dissemination
      utilization experiences.
AB  - As attitudes toward vocational activities for individuals with disabilities have
      changed, the importance of long-term funding support and of planned training have
      become evident. Continued emphasis is needed on the values underlying the
      interest in and the empowering nature of employment rights.

PMID- 9262071
TI  - Implementing supported housing: current trends and future directions.
AB  - Supported housing, preferred by consumers and demonstrated as effective for
      individuals with psychiatric disabilities, has taken four approaches: residential
      services, intensive case management, hybrid, and homeless outreach. Evaluating
      the choices for local settings requires confronting issues of flexibility and
      responsibility.

PMID- 9262072
TI  - Knowledge and use of folic acid by women of childbearing age--United States,
      1997.
AB  - Each year in the United States, approximately 4000 pregnancies are affected by
      spina bifida and anencephaly. Babies born with spina bifida usually survive,
      often with serious disability, but anencephaly is invariably fatal. The B vitamin
      folic acid can reduce the occurrence of spina bifida and anencephaly by at least
      50% when consumed daily before conception and during early pregnancy. In 1992,
      the Public Health Service (PHS) recommended that all women of childbearing age
      who are capable of becoming pregnant consume 400 microg of folic acid daily.
      Folic acid can be obtained from multivitamins or certain other supplements and
      from some fortified breakfast cereals. It is found naturally in orange juice,
      green leafy vegetables, and beans; however, it is difficult to obtain the
      recommended 400 microg daily through diet alone. This report summarizes findings
      from a survey conducted during January and February 1997 that indicate modest
      increases since 1995 in knowledge about and consumption of folic acid among U.S.
      women aged 18-45 years and highlights the need for additional public health
      efforts to take full advantage of this prevention opportunity.

PMID- 9262073
TI  - Landmine-related injuries, 1993-1996.
AB  - During 1980-1993, the incidence of landmine-related injuries doubled, resulting
      in an estimated 2000 deaths or injuries each month. Approximately 120 million
      landmines are buried in 71 countries throughout the world, and 2-5 million new
      landmines are planted each year. Some countries, such as Afghanistan, Angola, and
      Cambodia, have approximately 10 million landmines each. Landmines can have
      profound medical, environmental, and economic consequences, particularly for the
      civilian populations of those countries burdened with landmines. However, the
      consequences of landmines extend beyond the borders of those countries. Health
      care workers and nongovernmental organizations are increasingly asked to assist
      emergency-affected, displaced, and refugee populations in regional conflicts,
      resulting in their increased exposure to landmines. This report describes three
      cases of landmine-related injury and illustrates the public health consequences
      of those injuries and the potential role for public health workers in preventing
      those injuries.

PMID- 9262074
TI  - Asthma hospitalizations and readmissions among children and young adults-
      Wisconsin, 1991-1995.
AB  - Asthma is the most frequent reason for preventable hospital admissions among
      children. During 1980-1993, national asthma surveillance demonstrated increasing
      rates of hospital admission for persons aged <25 years. These increasing rates
      could be attributed to an increase in either the number of persons admitted,
      readmitted, or both. To determine the number of persons with asthma sufficiently
      severe to require hospitalization and to characterize admission/readmission
      patterns for persons with asthma, the Wisconsin Department of Health and Family
      Services (WDHFS) analyzed data from the Wisconsin Asthma Surveillance System
      (WASS). This report summarizes the findings from WASS, which indicate that,
      during 1991-1995, an annual average of 18% of all asthma admissions among
      Wisconsin residents aged <25 years were readmissions.

PMID- 9262075
TI  - Validation and interdependence with patient-variables of the influence of
      procedural variables on early and late survival after CABG. K.U. Leuven Coronary
      Surgery Program.
AB  - OBJECTIVE: First to identify the patient-, procedural- and surgical experience
      variables influencing the early and late survival after CABG. Second to identify
      patients likely to benefit, and those unlikely to benefit, from technical details
      aimed at improving the results of coronary artery bypass grafting (CABG).
      METHODS: A consecutive series of 9600 patients who underwent CABG using a variety
      of revascularization methods between 1971 and 1992 were followed with 99.9%
      success. A multivariable time-related analysis was performed. Patient-specific
      predictions and nomograms were constructed from it to explore and validate the
      influences and interdependences of patient-variables with variations in details
      of the procedure. RESULTS: The 1-, 10- and 20-year risk-unadjusted survival was
      97, 81 and 50% respectively. Patient-variables influencing early survival
      included severity of symptoms, patient presentation and extent of coronary
      disease, while late survival was influenced importantly by left ventricular
      function and cardiac and non-cardiac comorbidity. Technical details of the
      operation influencing early survival included use of endarterectomy, while
      details such as use of arterial grafting, extensiveness of sequential grafting,
      completeness of revascularization and extent of grafting to small coronaries
      influenced late survival to a highly variable degree. CONCLUSION: The early
      survival is neither improved nor worsened by single, multiple, sequential or
      complete arterial coronary reconstruction. The late survival is modestly improved
      with the use of an arterial graft to a major vessel, preferably but not
      exclusively to the anterior descendens, except for patients with limited life
      expectancy. Differences in time-related survival with and without an arterial
      graft are nearly the same across all levels of ejection fraction. No late
      beneficial or detrimental effect was identified with more extensive use of
      arterial reconstructive surgery in multisystem disease.

PMID- 9262076
TI  - Minimally invasive thoracoscopically assisted coronary artery bypass surgery.
AB  - OBJECTIVE: Minimally invasive techniques have been widely used in other surgical
      fields including video-assisted thoracic surgery (VATS) in thoracic surgery.
      These concepts are now being applied to cardiac surgery. The opportunities to
      make cardiac surgery less invasive include elimination of the median sternotomy
      incision, elimination of cardiopulmonary bypass and no manipulation of the aorta.
      MATERIALS AND METHODS: From January 1992 through September 1996, various aspects
      of minimally invasive cardiac surgery have been examined in the inanimate
      endoscopic trainer, animal model, human cadaver and in human clinical studies.
      Techniques of endoscopic sutured anastomosis as well as alternatives to suturing
      were first perfected in the inanimate trainer. Twenty animals then underwent
      endoscopic coronary artery bypass using the left internal mammary artery to the
      left anterior descending with circulatory support from an axial flow pump. Fifty
      eight minimally invasive coronary artery bypass procedures have been performed in
      humans using thoracoscopic assistance for internal mammary artery harvest.
      RESULTS: One hundred fifty endoscopic coronary anastomoses were performed in the
      inanimate trainer with the endoscopic suturing technique being the preferred
      method. Time required to perform an anastomosis decreased from greater than 60
      min to a mean of 20 min as technique and instruments were developed. In animals,
      methods of access as well as enabling surgical instruments to allow crossclamp of
      the aorta and performance of the anastomosis were developed. Fifty-eight humans
      underwent coronary artery bypass using the left internal mammary artery placed to
      the left anterior descending under direct vision through a limited anterior
      thoracotomy on a beating heart. The procedure was successful in 52 patients with
      conversions required in six patients. Techniques were developed for
      immobilization for performance of the anastomosis. DISCUSSION: The ability to
      perform an endoscopic anastomosis still remains the rate limiting step for
      totally endoscopic coronary artery bypass surgery. The present MIDCAB (minimally
      invasive direct coronary artery bypass grafting) procedure is a significant
      advance in cardiac surgery, but still has limitations that make performance of an
      exact anastomosis still somewhat difficult and applicable only to single-vessel
      disease. Present efforts are directed toward extending the MIDCAB procedure by
      various immobilization and circulatory support devices and combining the MIDCAB
      procedure with catheter techniques for treating more advanced disease.

PMID- 9262077
TI  - Clinical data and histological features of transmyocardial revascularization with
      CO2-laser.
AB  - OBJECTIVE: TMR is a modern therapeutic approach in the treatment of patients with
      severe chronic ischemic cardiac disease. Clinical data from world-wide over 1800
      TMR-treated patients shows that TMR can improve cardiac status in cases without
      preoperative congestive heart failure. The mechanisms underlying beneficial TMR
      effects are not well understood. METHODS: The 61 patients of the Hamburg
      University TMR-trial were treated with a CO2-laser. Clinically, both a 6 and a 12
      months follow-up were performed. Pathologically, hearts from four patients who
      died 3 (2 persons), 16 and 150 days after TMR, respectively, were examined by
      trichrom-and immunostaining (anti-collagen types I and III). RESULTS: In a 6
      months follow-up clinical data indicates that TMR was able to improve clinical
      status in 50 of 61 laser-treated patients (82%), whereas 5 (8.2%) did not show
      any benefit evaluated by CCS grading and six (9.8%) died. CCS grade reduction was
      found in 22 patients with a 12 months follow-up (28 patients still in
      evaluation). Days 30, mortality amounted to 6.5%; late mortality (over 30 days)
      was 3.3%. Histopathological investigations revealed tissue remodeling comparable
      with different stages of wound healing. The cicatricial tissue in the original
      laser-created channels displayed a stronger immunostaining for collagen type III
      than for type I. CONCLUSIONS: Clinically, TMR improves cardiac function in some
      patients with severe ischemic cardiac disease, but pathophysiological data as
      well as morphological features from human myocardium could not explain this
      phenomenon. Therefore, TMR treatment should be used only as 'the last chance' in
      patients with severe angina pectoris.

PMID- 9262078
TI  - Predictors of early and overall outcome in coronary artery bypass without
      cardiopulmonary bypass.
AB  - OBJECTIVE: Cardiopulmonary bypass in coronary artery bypass graft operations may
      adversely affect the outcome especially in high-risk patients. The purpose of
      this study is to evaluate results of coronary artery bypass performed without
      cardiopulmonary bypass, in a relatively high-risk cohort, and to identify
      predictors of unfavorable outcome. METHOD: Three hundred and thirteen (313)
      patients, 246 (79%) of whom had high-risk conditions, who have a coronary anatomy
      suitable for coronary artery bypass surgery without cardiopulmonary bypass,
      underwent this procedure between December 1991 and July 1995. Mean number of
      grafts/patient was 1.8 (1-5), and only 71 patients (23%) received a graft to the
      circumflex coronary system. RESULTS: Early unfavorable outcome events included
      operative mortality (12 patients, 3.8%), nonfatal perioperative myocardial
      infarction (eight patients, 2.6%), emergency reoperation (three patients, 0.9%),
      sternal infection (five patients, 1.6%), and nonfatal stroke (two patients,
      0.6%). Multivariate analysis revealed angina pectoris class IV (odds ratio 5.4)
      and age > or = 70 years (odds ratio 5.0) as independent predictors of early
      mortality. Preoperative risk factors such as repeat coronary artery bypass
      grafting (50 patients, 16%), ejection fraction < or = 0.35 (85 patients, 27%),
      acute myocardial infarction (86 patients, 28%), cardiogenic shock (ten patients,
      3.2%), chronic renal failure (25 patients, 8%), chronic obstructive pulmonary
      disease (20 patients, 6%), and peripheral vascular disease (51 patients, 16%) did
      not increase early mortality. During 33 months of follow-up (range 1-57 months),
      there were 42 deaths, at least 16 cardiac-related (one and four years actuarial
      survival of 90% and 76% respectively), and 39 patients (12.5%) in whom angina
      returned. Calcified aorta (odds ratio 2.6) and old myocardial infarction (odds
      ratio 1.8) were independent predictors of overall unfavorable events.
      CONCLUSIONS: Coronary artery bypass grafting without cardiopulmonary bypass can
      be performed with relatively low operative mortality in certain high-risk
      subgroups of patients; however, an increased risk of graft occlusion is a
      potential disadvantage. This procedure should therefore be considered only for
      patients with suitable coronary anatomy, in whom cardiopulmonary bypass poses a
      high risk. Although the risk of stroke is relatively low, the procedure is still
      hazardous for patients aged 70 years and over.

PMID- 9262079
TI  - Re-do cardiac surgery in patients over 70 years old.
AB  - OBJECTIVE: This study was conducted in order to determine the outcome of cardiac
      re-operations in patients over the age of 70. METHODS: All patients who underwent
      're-do' cardiac surgery at our institution, between January 1987 and October 1995
      were identified. The case notes of patients over the age of 70 were reviewed
      retrospectively and follow-up was by telephone. RESULTS: A total of 687 re-do
      operations were performed during this 8 years and 9 months period. Operations,
      110 (16%) were on patients aged 70 years and over (CABG 54, MVR 32, AVR 9, AVR +
      MVR 5, MVR + CABG 4, AVR + CABG 3, repair of paraprosthetic leak 2 and closure of
      VSD 1). Operations, 63 (57%) were elective and 42 (38%) were urgent. The median
      age was 73 years (range 70-82) and 64 patients (58%) were male. Pre-operatively,
      78 patients (72%) were NYHA functional class III/IV and 55 (50%) had
      angiographically impaired left ventricular function (ejection fraction < 50%).
      The overall operative mortality was 7% (8/110). Median ITU stay was one night
      (range 1-21) and hospital stay was 7 days (range 5-35). Major in-hospital
      complications included resternotomy in five patients (5%), permanent stroke in
      three (3%), renal failure requiring haemodialysis in two (2%) and heart block
      requiring permanent pacing in two (2%). At a median follow-up of 34 months (range
      2-101), 69 of the 77 patients alive at follow-up (90%) were NYHA functional class
      I/II. CONCLUSIONS: 'Re-do' cardiac surgery in patients over the age of 70 carries
      an acceptable operative morbidity and mortality with a good functional
      improvement at medium term follow-up.

PMID- 9262080
TI  - Aortic root replacement with human tissue valves in aortic valve endocarditis.
AB  - OBJECTIVE: Aortic allograft and pulmonary autograft aortic root replacement in
      native and prosthetic aortic valve endocarditis are evaluated and risk factors
      for hospital death are assessed by univariate risk factor analysis. METHODS: From
      April 1989 to May 1996, 59 patients with aortic valve endocarditis (27 native; 32
      prosthetic) underwent aortic root replacement with a human tissue valve. Mean age
      was 53.4 +/- 12.3 years; 46 patients (78%) were male. The mean preoperative NYHA
      functional class was 3.4. The predominant infective organisms were streptococci
      (30%) in the native valve group and staphylococci (30%) in the prosthetic valve
      group. In native valve endocarditis, valve destruction (32%) was the predominant
      finding. Abscesses, either annular (29%) or subannular (36%) and valve dehiscence
      (36%) were the most common findings in patients with prosthetic valve
      endocarditis. Partial or total ventriculo-aortic discontinuity (20%) and aortico
      mitral discontinuity (27%) were other important operative observations. A
      cryopreserved allograft was used in 53 patients (89.5%), the pulmonary autograft
      (Ross procedure) in 5 patients (8.5%), and a fresh antibiotic sterilized
      allograft root in one patient (2%). Mean aortic cross-clamp time was 131 +/- 32
      min. In active native and prosthetic valve endocarditis, intravenous antibiotics
      were continued for at least 6 weeks, monitored by serial CRP measurements.
      RESULTS: Hospital mortality was 8.5% (n = 5; 70% CL: 4.9-12.1%). Univariate risk
      factors for hospital mortality were age (P = 0.001), preoperative New York Heart
      Association functional class (P = 0.001), pre- (P = 0.001) and postoperative (P =
      0.001) renal insufficiency. Major complications were allograft failure (n = 1;
      2%), technical failure (n = 1; 2%) and false aneurysm formation at the proximal
      suture line (n = 1; 2%). Follow-up was complete, mean 33.1 +/- 20.1 months. Two
      late deaths occurred. Actuarial five year survival was 88.8% (70% CL: 80.0
      97.5%); actuarial five year freedom from recurrent endocarditis was 98.1% (70%
      CL: 94.5-100%). CONCLUSION: Allograft aortic root replacement is a valuable
      technique in the life threatening situations both of native and prosthetic aortic
      valve endocarditis with involvement of the annular and peri-annular region.

PMID- 9262081
TI  - Porcine mitral stentless valve mid-term clinical results.
AB  - OBJECTIVES: Time testing is essential with any valvular procedure, especially
      when a new concept is introduced such as the mitral stentless valve. Our purpose
      is to evaluate the results obtained over 4 years with this operation,
      particularly to attest the impact of preservation of annulo ventricular
      continuity on the long term results of these patients. METHODS: From March 1992
      to August 1996, 120 patients had their mitral valves replaced with a porcine
      stentless mitral valve. The observation period was 54 months with total patients
      follow-up of 3424 months with a mean of 28.5 months. The age ranged from 11 to 72
      years (mean 35.22 +/- 14.98). There were 73 females (60.8%) and 47 males (39.2%).
      The predominant etiology was rheumatic heart disease. Associated procedures were
      performed in 12 patients (10%), and the great majority of the patients were in
      functional class III and IV (NYHA). RESULTS: Hospital mortality occurred in seven
      patients (5.83%) non valve related except for one early case of endocarditis.
      Early reoperation related to technical failure were necessary in 4 patients
      without mortality. Follow-up was accomplished in 101 patients and ranged from 2
      to 54 months. Late reoperations were required in 16 patients (nine due to mitral
      insufficiency, five because of endocarditis and two for mitral stenosis). Most
      reoperations were related to technical failure. Among the 82 patients presently
      in control, 72 showed a competent mitral stentless valve, eight with stable mild
      mitral regurgitation and in two a decreased mitral orifice. Hemodynamic
      performance of the valve has been excellent in this group, particularly in
      patients with left ventricular dysfunction. CONCLUSION: Although technical
      complexity remains the main cause of reoperations with this valve, experience has
      shown that it not only provides preservation of the left ventricular function but
      also promised significant increase of the ejection fraction in patients with poor
      left ventricular function.

PMID- 9262082
TI  - Left ventricular remodelling and improvement in Freestyle stentless valve
      haemodynamics.
AB  - OBJECTIVE: To assess how left ventricular (LV) hypertrophy, geometry and function
      change after stentless aortic valve replacement for aortic stenosis, and to
      elucidate the physiological mechanism of the improvement in stentless valve
      haemodynamics. METHODS: 81 patients with aortic stenosis (age 75 +/- 6 years, 47
      male) underwent aortic valve replacement (plus CABG in 33 patients) with a
      Freestyle stentless porcine valve (mean size 23 +/- 2 mm). They were
      prospectively investigated by Doppler echocardiography at 2 weeks, 3-6, 12, and
      24 months after operation. Two hundred and forty-six echocardiograms were
      obtained and analysed. Aortic valve performance was assessed from its effective
      orifice area (EOA), the transvalvular increase in mean flow velocity (delta mV),
      the deceleration time of aortic flow velocity, and mean pressure drop (mPG). LV
      hypertrophy was assessed from LV mass index; LV geometry, from the ratio of wall
      thickness to the radius (T/R ratio) and LV function, from stroke volume index
      (LVSVI) and myocardial stroke work (SW). RESULTS: By 2 years after operation, LV
      mass index had fallen from 162 +/- 64 to 109 +/- 36, g/m2, and T/R ratio from
      0.61 +/- 0.25 to 0.43 +/- 0.10. LVSVI increased from 29.4 +/- 10 to 42 +/- 17,
      ml/m2, and myocardial SW from 3.1 +/- 1.6 to 5.2 +/- 2.2, mJ/cm3 (all P < 0.001
      by ANOVA), while LV outflow tract diameter remained unchanged. At the same time,
      stentless valve EOA increased from 1.59 +/- 0.75 to 2.2 +/- 0.72, cm2, and delta
      mV (from 82 +/- 31 to 49 +/- 24, cm/s) and mPG (from 9.7 +/- 5.0 to 5.2 +/- 3.7
      mmHg) both fell significantly (all P < 0.001 by ANOVA): as the deceleration time
      of aortic flow velocity increased from 153.6 +/- 64.1 to 202.7 +/- 37.6 ms (P <
      0.001 by ANOVA). CONCLUSION: After stentless aortic valve replacement, LV mass
      index and wall thickness both fall towards normal, and myocardial stroke work
      increases. These ventricular remodelling processes are accompanied by a more
      physiological flow jet at valve cusp level, which permits a greater stroke volume
      to be ejected with a smaller transvavular velocity increase, so that effective
      orifice area increases.

PMID- 9262083
TI  - Smoking after heart transplantation: an underestimated hazard?
AB  - OBJECTIVE: Risk factors for the development of vasculopathy and malignancies as
      the most important causes of morbidity and mortality after heart transplantation
      are not well defined. METHODS: Univariate and multivariate Cox regression
      analysis of the data derived from our 84 survivors of more than 3 months after
      orthotopic heart transplantation between 1984 and 1996. Measurement of
      carbonmonoxide-hemoglobin blood levels with an ABL 520 analyzer. RESULTS:
      Recipient or donor age, the mode of immunosuppression, total-, LDL- and HDL
      cholesterol, the HDL/LDL-ratio, triglycerides, hypertension, diabetes mellitus,
      CMV status and rejection episodes had no independent influence on total mortality
      or the occurrence of graft vasculopathy or cancer. By means of an intensive
      questionnaire (in case of deceased patients, by their relatives) and measurement
      of CO-Hb blood levels we detected a high rate of patients who smoked after
      transplantation (22/84 = 26%). Four patients confessed smoking after undergoing
      the blood test. Non-smokers were defined as denying it in the questionnaire and
      having CO-Mb levels < 2.5% in repeated measurements. All but one were smokers
      before heart transplantation. Mean consumption was 11 cigarettes per day. Five
      and 10 years survival was significantly reduced in smokers vs. non-smokers (37
      vs. 80% and 10 vs. 74%, respectively, P < 0.0001). Survival curves diverged
      dramatically after 4 years of observation. Smokers had a higher prevalence of
      transplant vasculopathy as revealed by coronary angiography and/or autopsy (10/22
      smokers vs. 2/62 non-smokers, P < 0.00001) and a higher rate of malignancies
      (7/22 smokers developed cancer, as compared to 4 cancers in 62 non-smokers, P =
      0.0001). The primary site of cancer was the lung in 5/6 smoking and lymphoma in
      all non-smoking cancer patients. CONCLUSIONS: Our data show that the prevalence
      of smoking after heart transplantation may be relatively high, especially in
      former smokers. Repeated measurements of CO-Hb could be helpful in its detection.
      Despite a relatively low cigarette count, smoking is a major risk factor of
      morbidity and mortality after heart transplantation (HTx). Approximately 4 years
      of exposure time is needed to uncover its negative influence. These findings
      should lead to aggressive smoking screening and weaning programs in every HTx
      center.

PMID- 9262084
TI  - Temporary loss of cardiac autonomic innervation after the maze procedure.
AB  - OBJECTIVE: Blunted sinus node response to exercise has been reported after the
      maze operation. We suggested the autonomic vegetative function of the heart to be
      disturbed after the maze procedure. METHODS: 17 patients, mean age 63 +/- 15
      years, with chronic atrial fibrillation for 49 +/- 46 months (range 5-65)
      underwent the maze procedure during mitral valve surgery. Bicycle stress test, 24
      h electrocardiography and heart rate variability were analysed in 11 patients
      after three and in six after 14 +/- 3 months. Spectral analysis within two
      frequency bands, vector analysis of the main circular resultant and influence of
      orthostasis and Valsalva manoeuvre on different R-R intervals were calculated.
      RESULTS: One patient died from a perioperative ischaemic stroke. At follow-up,
      all patients were in sinus rhythm. Heart rate reached 84 +/- 14%, the mean
      circular resultant was 60 +/- 48%, the ratio of the longest to the shortest R-R
      interval during the Valsalva manoeuvre was 92 +/- 8% and the ratio of maximal to
      minimal R-R interval after orthostasis was 98 +/- 4% of the age-adjusted normal
      value. Maximal workload was 116 +/- 31 watts. All patients had abnormal heart
      rate variability. Heart rate variability was significantly more blunted after
      three months, than after 14 months (P < 0.05). The minimal heart rate and the
      difference between the maximal and the minimal heart rate during the 24-h
      electrocardiography were significantly correlated to the number of normal
      physiological tests (r = -0.52; P < 0.05; r = 0.71; P < 0.005); for the maximal
      heart rate, there was a positive trend only (r = 0.44; P = 0.07). CONCLUSIONS:
      Early after the maze procedure, a nearly total denervation of the sinus node is
      present, similar as seen after heart transplantation, with partial restoration of
      the autonomic function after one year. The exercise capacity of the patients was
      satisfactory.

PMID- 9262085
TI  - Thoracotomy and thoracoscopy: postoperative pulmonary function, pain and chest
      wall complaints.
AB  - OBJECTIVE: Two different surgical accesses combined with standard pain management
      procedures are compared regarding early and intermediate pulmonary function and
      pain relief. METHODS: In a prospective study, 15 consecutive patients undergoing
      video-thoracoscopy for pulmonary wedge resection (group 1) were matched to 15
      patients undergoing standard postero-lateral thoracotomy for lobectomy (group 2)
      according to age, gender and preoperative pulmonary function. Postoperative pain
      control consisted of patient controlled analgesia in group 1 and epidural
      analgesia in group 2. Pain intensity was scored from 0-4. The predicted
      postoperative pulmonary function (FVC and FEV 1) after lobectomies was calculated
      from the preoperative value according to the extent of resection. A clinical
      measurement was obtained after a mean follow-up time of 4.2 months. RESULTS: The
      ratios of postoperative measured to predicted values of FVC and FEV1 for group 1
      compared with group 2 were 0.64 +/- 0.15 and 0.65 +/- 0.14 compared with 0.60 +/-
      0.19 and 0.59 +/- 0.13, resp. (both n.s.) at the first day postoperative; 0.92 +/
      0.18 and 0.95 /- 0.17 compared with 0.76 +/- 0.20 (P < 0.05) and 0.83 +/- 0.23
      (n.s.), resp. at hospital discharge; 0.98 +/- 0.10 and 0.94 +/- 0.14 compared
      with 1.01 +/- 0.17 (n.s.) and 1.10 +/- 0.17 (P < 0.05), resp. at follow-up. Pain
      intensity score one day after surgery ranged from 0.4 (resting position) to 1.6
      (coughing) for group 1, and from 0.3 to 1.2 for group 2. Thirty-six percent of
      the thoracoscopy patients and 33% of the thoracotomy group complained of
      persistent pain or discomfort on the site of the operation after 3-18 months.
      CONCLUSION: Post-thoracotomy pain can be effectively controlled with epidural
      analgesia and pain intensity is no higher than in patients after thoracoscopy who
      are managed with patient controlled analgesia. FVC is slightly more decreased
      after thoracotomy during the early postoperative period. FVC and FEV 1 approach
      the predicted values after four months in both groups. The rate of persistent
      pain is similar after thoracoscopy and thoracotomy.

PMID- 9262086
TI  - Experimental gluing of the bronchial stump after pneumonectomy in rats.
AB  - OBJECTIVE: The objective of this experimental study was to evaluate the
      usefulness of gelatin-resorcinol-dialdehyde adhesive in sutureless closure of
      bronchial stumps. METHODS: In 40 male Wistar rats bronchial stumps after left
      sided pneumonectomy were closed by gluing with gelatin-resorcinol-dialdehyde
      adhesive. For macroscopic and microscopic examination four animals were
      sacrificed on postoperative days 2, 7 and 14 each, 14 animals on postoperative
      days 28 and 120 each. RESULTS: On macroscopic examination the gelatin-resorcinol
      dialdehyde adhesive proved in all cases effective in tight bronchial stump
      closure. The adhesive did not cause local infection or necrosis of the bronchial
      stump nor other intrathoracic inflammatory complications. All animals survived
      and made an uncomplicated postoperative recovery. Microscopic examination
      revealed that the gelatin-resorcinol-dialdehyde adhesive initially evoked an
      acute inflammatory response with polymorphonuclear neutrophils predominating.
      After an intermediate stage characterized by a granulomatous reaction and
      resorption of the adhesive by multinucleated giant cells, 120 days
      postoperatively the bronchial stumps at the sites of previous gluing showed a
      regular fibrous scar tissue without inflammatory cells. CONCLUSION: The gelatin
      resorcinol-dialdehyde adhesive showed effective in closing bronchial stumps after
      pneumonectomy in rats. The clinical extrapolation of this effect to thoracic
      surgical patients is uncertain at this time.

PMID- 9262088
TI  - Post-intubation tracheal rupture. A report on ten cases.
AB  - OBJECTIVE: We wanted to evaluate the role of surgical and conservative therapy in
      the treatment of post-intubation tracheal rupture. METHODS: A retrospective study
      was performed on 10 consecutive patients (9 women and 1 man) treated over a 7
      year period. RESULTS: A tracheal rupture following double-lumen intubation was
      recognized and repaired at the time of lobectomy for lung cancer. Five patients
      with rents ranging from 2.5 cm to 5 cm underwent primary repair through a
      cervical collar incision (n = 3) or right posterolateral thoracotomy (n = 2).
      Three patients had small tears (about 1 cm in length) and were treated
      conservatively. Tracheostomy was performed in one patient with a 1.5-cm long
      laceration and extensive subcutaneous emphysema. Results were uniformly good.
      CONCLUSIONS: Early surgical repair is the preferred treatment for most patients
      with post-intubation tracheal ruptures. Conservative treatment may be a viable
      alternative for patients with small rents, in the absence of gross air leak, or
      for those judged unsuitable for surgery. The role of tracheostomy is limited by
      its potential for late sequelae.

PMID- 9262087
TI  - Characterization of pulmonary nodules and mediastinal staging of bronchogenic
      carcinoma with F-18 fluorodeoxyglucose positron emission tomography.
AB  - OBJECTIVE: To evaluate F-18 fluorodeoxyglucose positron emission tomography (PET)
      in terms of its sensitivity and specificity in diagnosing malignant pulmonary
      nodules and staging bronchogenic carcinoma. METHODS: A retrospective review of
      any patient that presented to the VA Palo Alto Health Care System with a
      pulmonary nodule between 9/94 and 3/96 revealed 49 patients (four female, 45
      male) age 37-85 (mean 63) with 54 pulmonary nodules who had: chest CT scan, PET
      scan; and tissue characterization of the nodule. Characterization of each nodule
      was achieved by histopathologic (N = 44) or cytopathologic (N = 10) analysis. Of
      the 49 patients, 18 had bronchogenic carcinoma which was adequately staged.
      Mediastinal PET and CT findings in these 18 patients were compared with the
      surgical pathology results. N2 disease was defined as mediastinal lymph node
      involvement by the American Thoracic Society's classification system. Mediastinal
      lymph nodes were interpreted as positive by CT if they were larger that 1.0 cm in
      the short-axis diameter. RESULTS: Sensitivity and specificity for the diagnosis
      of malignant pulmonary nodules using PET was 93 and 70%, respectively. All
      nodules (N = 3) that were falsely positive by PET scan were infectious in origin.
      All nodules (N = 4) that were falsely negative by PET were technically limited
      studies (outdated scanner, no attenuation correction, hyperglycemia) except for
      one case of metastatic adenocarcinoma. The sensitivity and specificity of PET in
      diagnosing N2 disease was 67 and 100%, compared with 56% and 100% for CT scan
      (not statistically significant). However, one more patient with N2 disease was
      correctly diagnosed by PET than by CT scan. CONCLUSION: PET is a valuable tool in
      the diagnosis and management of pulmonary nodules and may more accurately stage
      patients with bronchogenic carcinoma than CT scanning alone.

PMID- 9262089
TI  - Malignant neoplasms following cardiac transplantation.
AB  - OBJECTIVE: Malignancies have long been recognized as a complication of long
      lasting immunosuppressive therapy. We reviewed our experience to investigate the
      incidence and the spectrum of non cutaneous de novo malignant neoplasms. METHODS:
      Between March 1987 and March 1996, 296 patients underwent 303 cardiac
      transplantation in our service. The population at risk consists of all patients
      surviving more than 1 month after transplantation, leading to a total of 267
      patients. A triple-immunosuppressive therapy was employed. Moderate doses of
      antilymphocyte globulin was used as an induction immunotherapy. RESULTS:
      Neoplasms developed in 18 (6.7%) of the 267 patients at risk. Seventeen patients
      were male. Mean age was 56 +/- 7 years. Fourteen patients (78%) reported a
      significant smoking history. Mean interval between transplantation and clinical
      diagnosis was 36 months. Lung neoplasms (especially adenocarcinoma) were the most
      commonly encountered tumors (11 of 268 patients, 4.1%). Three Non-Hodgkins'
      Lymphoma (NHL) were identified (1.1%). No Kaposi's sarcoma were diagnosed. Mean
      survival after a diagnostic of tumor was 11.7 months. CONCLUSIONS: The incidence
      of NHL is low in our transplant recipients. Conversely, we observed a high
      incidence of lung neoplasms (especially adenocarcinoma) which can be correlated
      with a heavy cigarette use in the study population.

PMID- 9262090
TI  - Management of the univentricular connection: are we improving?
AB  - OBJECTIVE: To assess the impact of the bidirectional cavopulmonary shunt, total
      cavopulmonary connection, and baffle fenestration on outcome of the Fontan
      operation in our unit. METHOD: We reviewed 123 bidirectional cavopulmonary shunts
      and 264 Fontan operations performed from 1980 to 1995. Analysis of pulmonary
      artery size (right and left main and lower lobe branches) before and after
      bidirectional cavopulmonary shunt was performed. Outcome of the Fontan operation
      was analysed in various time periods to assess the effect of prior bidirectional
      cavopulmonary shunt, use of the lateral tunnel, and fenestration. RESULTS:
      Operative risk for the bidirectional cavopulmonary shunt was 4% (CI = 2-10%) with
      a survival of 89% (CI = 83-95%) at 36 months. Probability of conversion to Fontan
      operation at 36 months was 49% (CI = 38-61%). Pulmonary artery size (Nakata and
      lower lobe indices) fell after bidirectional cavopulmonary shunt (P = 0.0006).
      Fontan risk dropped from 8.5% (1980-1987) to 1.8% (1988-1995) (P = 0.02),
      coinciding with the use of the bidirectional cavopulmonary shunt. There was no
      further risk reduction after introduction of the lateral tunnel and baffle
      fenestration, although these comparisons are limited by relatively small numbers.
      Duration of hospital stay related to pleural effusions was lowest for patients
      with a fenestrated lateral tunnel operation (P < 0.05). CONCLUSION: The
      bidirectional cavopulmonary shunt is a suboptimal stimulus for pulmonary artery
      enlargement, but may reduce the risk of Fontan operation in selected children.
      Fenestrated lateral tunnel operations have reduced the duration of postoperative
      pleural effusions.

PMID- 9262091
TI  - Alternative techniques for surgical management of recoarctation.
AB  - OBJECTIVE: To evaluate the different surgical options in patients with
      recoarctation and minimal collaterals. METHODS: Thirty-three cases operated on
      between January 1980 and January 1995 were reviewed. Initial repair was end-to
      end anastomosis in 16 patients, subclavian artery aortoplasty in 10, synthetic
      patch aortoplasty in 4 and bypass conduit in 3 patients. Age at reoperation was
      7.5 +/- 5.2 years (1-17 years). Pressure gradient was 20-48 Torr (33 +/- 9).
      Upper extremity resting or exercise systemic hypertension was present in all. In
      18 patients recoarctation was repaired using subclavian artery aortoplasty (n =
      15) or synthetic patch aortoplasty (n = 3); alone in 9, with temporary
      heparinized bypass in 2, or in addition to placement of ascending aorta to
      descending aorta conduit as a permanent bypass through a left thoracotomy in 9.
      In 13 patients a conduit was interposed between ascending aorta and descending
      aorta through a right thoracotomy. In one patient recoarctation segment was
      patched on cardiopulmonary bypass through a midsternotomy. RESULTS: There was no
      mortality or complications. All patients had no echocardiographic pressure
      gradients across recoarctation on 5 +/- 3.4 years follow-up. Persistent systemic
      hypertension following recoarctation repair was present in 3/8 patients (37%)
      operated on at age greater than 10 years, but has been resolved in all 25
      patients less than 10 years of age (P = 0.02). CONCLUSIONS: Use of ascending
      aorta to descending aorta conduit, either alone through a right thoracotomy, or
      as permanent bypass in combination with patching the recoarctation through a left
      thoracotomy provides safe and excellent relief of obstruction.

PMID- 9262092
TI  - Repair for aneurysms of the entire descending thoracic aorta or thoracoabdominal
      aorta using a deep hypothermia.
AB  - OBJECTIVE: Replacement of the entire descending aorta or of the thoracoabdominal
      aorta still has a significant risk for postoperative paraplegia. Surgical
      strategies using a deep hypothermia to protect the spinal cord or viscera are
      discussed. METHODS: From April 1994, 25 patients underwent graft replacement of
      the entire descending aorta (13 patients) or thoracoabdominal aorta (12 patients)
      using a deep hypothermia. Five patients had atherosclerotic aneurysms and 20 had
      aortic dissection. There were 20 males and 5 females, whose age ranged from 26 to
      72 years old, 47 years old in average. Surgery consisted with proximal
      anastomosis using deep hypothermia (18 degrees C) with retrograde cerebral
      perfusion by elevating central venous pressure to 20 mmHg, reconstruction of the
      intercostal arteries, and distal open anastomosis, while perfusing the brain and
      heart. Proximal open anastomosis was used with retrograde cerebral perfusion
      technique in 18 patients. Averaged number of reconstructed intercostal arteries
      was 2.1 for each patient. RESULTS: No early mortality was found and one patient
      died of respiratory failure 6 months after surgery. One patient had a
      postoperative stroke and one had a delayed onset of paraplegia 2 days after
      operation. The cause of paraplegia was secondary hypoxemia and hypotension due to
      pneumonia. CONCLUSION: Utilization of the deep hypothermia in surgery for
      aneurysms of the entire descending aorta or of the thoracoabdominal aorta
      provided an adequate protection of the spinal cord as well as the abdominal
      viscera, eliminated clamp injury or cerebral embolization of debris or thrombi,
      and afforded excellent surgical exposures.

PMID- 9262093
TI  - Resection of hypernephromas with vena caval or right atrial tumor extension using
      extracorporeal circulation and deep hypothermic circulatory arrest: a
      multidisciplinary approach.
AB  - OBJECTIVE: Among retroperitoneal tumors, renal cell carcinoma most often invades
      the retrohepatic inferior vena cava or the right atrium. Even in these cases,
      radical nephrectomy may be performed with curative intention. The aim of this
      retrospective study was to elucidate the impact of cardiopulmonary bypass and
      hypothermic circulatory arrest on surgical complications, primary mortality, and
      long-term survival. PATIENTS AND METHODS: From Jan. 1981 till Aug. 1996, 44
      patients were operated upon for renal cell carcinoma with advanced vena caval
      extension. The patients were divided into two groups. In 19 cases
      (Cardiopulmonary Bypass Group), extracorporeal circulation and deep hypothermic
      circulatory arrest was used. The Conventional Technique Group comprised 25
      patients who had radical nephrectomy, paraaortic lymphadenectomy and extirpation
      of the intracaval tumor thrombus applying common principles in vascular surgery.
      The median age was 59 years with a range from 42 to 78 years in the
      Cardiopulmonary Bypass Group, and 60 years, ranging from 22 to 72 years, in the
      Conventional Technique Group. In addition, both groups did not differ in gender,
      UICC TNMG staging classification, and perioperative risk factors. A review of the
      patient charts was done and surveys were sent to survivors or nearest of kin.
      Wilcoxon test and log-rank test were used as appropriate. RESULTS: A lower
      intraoperative complication rate was found in patients who had surgery using
      cardiopulmonary bypass. This was especially true with embolization of the tumor
      thrombus into the pulmonary arteries: 0.0% in Cardiopulmonary Bypass Group and
      16.0% in Conventional Technique Group (P < 0.05). Severe hemorrhage occurred in
      10.5% (Cardiopulmonary Bypass Group) and 16.0% (Conventional Technique Group).
      This translated into a significantly lower perioperative mortality in the
      Cardiopulmonary Bypass Group when compared to the Conventional Technique Group
      (5.6 and 16.0%, respectively). In spite of these results, differences in long
      term survival did not reach statistical significance. But, a trend to superior
      long-term survival was apparent. The mean survival was 1289 +/- 278 days in the
      Cardiopulmonary Bypass Group and 746 +/- 166 days in the Conventional Technique
      Group. CONCLUSIONS: Due to acceptable long-term results, the resection of
      hypernephromas showing extensive vena caval invasion seems to be justified. The
      use of cardiopulmonary bypass and hypothermic circulatory arrest is able to
      decrease primary morbidity and mortality. However, the influence on long-term
      survival remains to be proven.

PMID- 9262094
TI  - Successful treatment of primary pneumococcal multilocular mycotic aneurysms.
AB  - We report the case of a patient with five primary pneumococcal multilocular
      mycotic aneurysms located in the left femoral artery, the descending thoracic
      aorta and the right internal iliac artery. A successful treatment combining three
      different procedures was performed, including the use of two cryopreserved
      thoracic homografts. At a 54-month follow-up, the patient is alive and leads a
      normal life. Regular evaluation including computed tomographic scans of the
      thorax and abdomen showed no recurrence of infectious aneurysmal process.
      Moreover, this latter examination confirmed no dilatation nor significant
      calcifications of the thoracic arterial allograft, though chest roentgenogram
      showed discrete calcifications along the borders at the 50th month.

PMID- 9262095
TI  - Aneurysm of aberrant right subclavian [corrected] artery arising from
      diverticulum of Kommerell. Report of a case with tracheal compression.
AB  - A 74-year-old woman presented with severe dyspnea without dysphagia. Computed
      tomographic scans and Digital subtraction angiography revealed the left aortic
      arch with an aberrant right subclavian artery arising from the Kommerell's
      diverticulum and tracheal compression. The aortic arch and the Kommerell's
      diverticulum were aneurysmal and were responsible for this compression. Surgical
      relief was accomplished by replacement of the aortic arch and reconstruction of
      the four brachiocephalic vessels with vascular prostheses through a median
      sternotomy incision extending into the right supraclavicular region.

PMID- 9262096
TI  - Closure of a bronchopleural fistula by midsternal approach in three patients with
      previous aortocoronary bypass grafting.
AB  - The feasibility of midsternal approach for closure of bronchopleural fistula is
      demonstrated in three patients who had previously undergone sternotomy for
      aortocoronary bypass grafting.

PMID- 9262097
TI  - Malignant peripheral nerve sheath tumour: a rare tumour and an unusual
      intrapericardial presentation.
AB  - A 62-year-old man presented with superior vena caval obstruction and was found to
      have a tumour in the pericardial cavity. This was diagnosed as a Malignant
      Peripheral Nerve Sheath Tumour (MPNST), an uncommon sarcoma that is exceedingly
      rare in this location. Stigmata of von Recklinghausen's disease were absent.
      Antibodies to a panel of immunoreactive markers were utilised to establish the
      diagnosis and exclude other tumours. The utility of such an approach in this kind
      of situation is briefly discussed.

PMID- 9262098
TI  - Ectopic thyroid malignancy in the right ventricle of the heart.
AB  - In a 55-year-old woman (10 years after subtotal thyroidectomy for follicular
      adenoma) echocardiography revealed a 25 x 23-mm tumour in the right ventricular
      outflow tract. The successfully removed tumour appeared to be a follicular
      carcinoma. Subsequently, there has been no clinical and laboratory evidence for
      another site of metastasis or ectopic thyroid. The whole body 131I scan showed
      only correct radioiodine uptake in the place of cervical residual thyroid gland.
      We believe this is the first description of follicular carcinoma in cardiac
      ectopic thyroid.

PMID- 9262100
TI  - Images in cardio-thoracic surgery. Mycotic aneurysms of the thoracic aorta caused
      by Streptococcus pneumoniae.

PMID- 9262099
TI  - Extrusion of Teflon aortic pledgets from a sternal wound six years after cardiac
      surgery.
AB  - We present a case of a cardiac surgery patient with a persistent low-grade
      discharge from his sternal wound for over six years. It finally healed when some
      suture material and Teflon felt pledgets were extruded. These had been used
      intraoperatively to close the aortic cannulation site. The extrusion of
      prosthetic material from this site after this length of time has never been
      described.

PMID- 9262101
TI  - Minimal pulmonary resection and minor chest procedures: is pleural drainage
      systematically necessary?

PMID- 9262102
TI  - Emergent axial computed tomography in the diagnosis and management of blunt
      thoracic trauma.
AB  - The purpose of our retrospective study was to evaluate the efficacy of chest
      computed tomography (CCT) in comparison with conventional chest X-ray (CXR) in
      diagnosis and management of acute blunt trauma patients.

PMID- 9262103
TI  - Thoracoscopic pleurodesis for prolonged (or intractable) air leak after lung
      resection.
AB  - Air leaks are common after lung resection, and normally seal with conservative
      therapy. Re-thoracotomy is rarely indicated. We present three patients with
      prolonged air leak and partial pneumothorax treated by thoracoscopy. Complete
      lung re-expansion followed immediately. Postoperative air leak was minimal. The
      chest tubes were removed after three or four days. Complete division of adhesions
      and sealing of the leak(s) are essential. Thoracoscopy may be the method of
      choice for prolonged air leak unresponding to conservative therapy provided the
      bronchial stump or suture have been verified by endoscopy.

PMID- 9262104
TI  - Valve-in-valve or super imposition of mechanical valves on impacted
      bioprostheses.

PMID- 9262105
TI  - Anomalous origin of the right coronary artery.

PMID- 9262107
TI  - Lung cancer.

PMID- 9262106
TI  - Comparison of costs between video-assisted thoracic surgery (VATS) and
      thoracotomy.

PMID- 9262108
TI  - Diagnostic tests for lung cancer.
AB  - Bronchogenic carcinoma is the leading cause of cancer death in both men and women
      in the United States. There has been little impact on the overall mortality from
      lung cancer in the past 20 years. Diagnostic tests such as routine chest x-ray
      and sputum cytology have proven to be ineffective in altering this mortality. The
      identification of risk factors, including obstructive lung disease and familial
      tendencies to develop lung cancer, may allow for specific strategies that will
      impact this mortality. Additionally, biological markers are being identified in
      sputum specimens that may allow identification of premalignant changes prior to
      morphologic changes seen in sputum cytology. Radiologic testing such as CT scans
      with contrast enhancement and positive emission tomography may also aid in the
      early detection of peripheral lung nodules. It is through the development of
      these new technologies that we have an opportunity to alter overall lung cancer
      mortality. Here we review several articles reporting exciting new diagnostic
      technology.

PMID- 9262109
TI  - Pathology of lung cancer.
AB  - In this review, we focus on a number of developments pertaining to lung cancer
      diagnosis, entirely restricted to those parameters assessable by light
      microscopy. A number of discrete areas of interest stand out in 1996 related to
      the pathology of lung cancer. Aberrant p53 expression continues to be debated as
      an independent prognostic factor in nonsmall cell carcinoma. Neuroendocrine
      differentiation may be an independent prognostic factor in nonsmall cell
      carcinoma and new associations with the protein product of the bcl-2 oncogene
      have been described. Angiogenesis continues to arise as a predictor of metastatic
      potential in lung cancer. Finally, we review conceptual aspects of carcinogenesis
      from atypical adenomatous hyperplasia to bronchioloalveolar carcinoma, in
      addition to a variety of individual tumor-related issues associated with
      progression, response to chemotherapy, and survival.

PMID- 9262110
TI  - Intrathoracic neoplasms other than bronchogenic carcinoma.
AB  - Intrathoracic neoplasms other than bronchogenic carcinoma comprise a disparate
      group of tumors that have in common an anatomic location within the thorax. For
      the purposes of this review, they are divided into three categories: pulmonary
      metastases from locations other than the thorax, mediastinal neoplasms, and
      unusual primary lung neoplasms. This article reviews the recent literature;
      discusses evolving strategies for imaging, diagnosis, and treatment; and presents
      promising research developments.

PMID- 9262111
TI  - Disorders of pulmonary circulation.

PMID- 9262112
TI  - Diagnostic strategies for the management of patients with clinically suspected
      deep-vein thrombosis.
AB  - Given the perceived inaccuracy of clinical diagnosis, patients with suspected
      deep vein thrombosis should have objective testing. Due to the inherent
      limitations of the reference method (contrast venography), several diagnostic
      strategies using noninvasive tests have been developed. These strategies share
      two components: anticoagulant therapy is initiated only in patients with an
      abnormal test, and serial testing is performed in patients with an initial normal
      test result. A thorough search of the literature was done to identify all studies
      that have evaluated the feasibility, accuracy, and safety of diagnostic
      strategies in patients with clinically suspected deep vein thrombosis. The safety
      of the individual diagnostic strategies was expressed as the total rate of venous
      thromboembolic complications. Feasibility was expressed as the mean number per
      patient of extra visits to the hospital and additional tests per patient. A total
      of 12 reports qualified for the analysis. The diagnostic strategies included
      venography, serial impedance plethysmography with and without 125I-fibrinogen leg
      scanning, serial ultrasound imaging with and without D-dimer determination,
      serial ultrasound imaging in combination with a clinical score, and a diagnostic
      work-up including ultrasound imaging, impedance plethysmography, D-dimer
      determination, and a clinical score. The observed venous thromboembolic
      complication rates varied between 0.4% and 2.6%. Feasibility was lowest for the
      initial serial impedance plethysmography strategy (mean number of extra hospital
      visits and mean number of additional tests, 4.1 per patient). Strategies that
      used the D-dimer test complimentary to ultrasound imaging or the combination of
      impedance plethysmography and a clinical score performed best (mean number of
      extra hospital visits and mean number of additional tests, approximately 0.3 per
      patient). All available noninvasive diagnostic strategies are as accurate and
      safe as contrast venography for the treatment of patients with clinically
      suspected deep vein thrombosis. The recently introduced simplified diagnostic
      strategies allow treatment decisions to be made on the day of presentation in
      most patients.

PMID- 9262113
TI  - The role of D-dimer in the diagnosis of venous thromboembolism.
AB  - The diagnosis of venous thromboembolism remains a clinical challenge. D-dimer, a
      specific breakdown product of crosslinked fibrin, is a sensitive marker for acute
      thrombosis. Recent studies have demonstrated that D-dimer testing has a promising
      role as an exclusionary test in patients with suspected deep vein thrombosis or
      pulmonary embolism. However, a wide range of sensitivities and specificities has
      been reported for D-dimer assays because of inter- and intra-assay variations and
      differences in patient populations. New rapid D-dimer enzyme-linked immunosorbent
      assays and the whole blood agglutination assay SimpliRED (Agen Biomedical,
      Brisbane, Australia) D-dimer have high negative predictive values. Recent studies
      have shown that a normal result on a SimpliRED assay combined with a low pre-test
      probability or normal result on impedance plethysmography reliably excludes
      venous thrombosis. Latex agglutination assays are relatively insensitive as
      screening tests and should not be used. Management studies are underway and will
      further delineate the role of D-dimer testing in patients with suspected venous
      thromboembolism.

PMID- 9262114
TI  - New imaging techniques for the diagnosis of pulmonary embolism.
AB  - Pulmonary embolism (PE) remains a common cause of illness and death. Appropriate
      therapy requires timely diagnosis, but the currently available noninvasive
      diagnostic methods lack adequate sensitivity and specificity. In particular the
      vast majority of ventilation-perfusion scans are unable to confirm or reliably
      exclude PE, cannot differentiate between acute and chronic PE, and provide no
      clues about possible alternate explanations of presenting symptoms (even if PE
      can be excluded). Although the precise role of these scans in the diagnosis of PE
      remains to be clarified, recent advances appear to ensure a place for magnetic
      resonance imaging and helical computed tomography in the diagnostic evaluation of
      PE in the near future.

PMID- 9262115
TI  - Duration of anticoagulant treatment for venous thrombosis.
AB  - Patients with deep-vein thrombosis require long-term anticoagulant treatment to
      prevent recurrent venous thromboembolism. Anticoagulant treatment should be
      continued for at least 3 months in patients with a first-episode of proximal deep
      vein thrombosis. In patients with a second-episode of venous thromboembolism,
      treatment should probably be continued for at least 1 year, because stopping
      treatment at 3 to 6 months is associated with a high rate of recurrent venous
      thromboembolism. Indefinite treatment may be indicated in patients with a second
      episode of venous thromboembolism, but further clinical trials are required to
      clarify the risk and benefit of indefinite treatment. Further clinical trials are
      also required to determine if a longer course of treatment is indicated for
      subgroups of patients based on clinical characteristics and laboratory features
      (such as those with idiopathic thrombosis versus postoperative thrombosis, and
      those with or without identifiable molecular markers of a high risk of recurrent
      venous thromboembolism such as the factor V Leiden gene mutation).

PMID- 9262116
TI  - Current status on new anticoagulant and antithrombotic drugs and devices.
AB  - Several new drugs for the management of thromboembolic disorders have recently
      become available. Low-molecular-weight heparins are being evaluated for the
      prophylaxis of medical and surgical deep venous thrombosis and pulmonary
      embolism; for the treatment of pre-existing thrombosis; and for cases of coronary
      syndrome (unstable angina, myocardial infarction), thrombotic and ischemic
      stroke, interventional cardiology, pregnancy, cancer, and transplantation
      associated thrombosis. A chemically synthesized heparin pentasaccharide, which
      has purely anti-factor Xa activity and does not induce thrombocytopenia, is also
      in clinical trial. Thrombin inhibitors, such as hirudin and argatroban, are a
      practical anticoagulant substitute where heparin cannot be used. They are also
      useful for the management of coronary syndrome and as adjunct therapy. The
      antiplatelet agent ticlopidine and its analogue, clopidogrel, which does not
      produce blood dyscrasia, are effective for the secondary prevention of thrombotic
      stroke and the management of combined arterial thrombotic syndromes. Glycoprotein
      targeting antibodies, synthetic derivatives, and peptides (some of which are
      orally bioavailable) have added a new dimension to the management of arterial
      thrombosis and high-risk patients having angioplasty. Plasma-derived agents, such
      as antithrombin III, are available for the management of thrombophilia and
      disseminated intravascular coagulation. Compression devices and the foot pump,
      alone and in combination with pharmacologic agents, have been used successfully.
      Combination therapy using various agents in different proportions have also been
      found useful. Although there is much enthusiasm in this quickly developing area
      and clinical trials are demonstrating the antithrombotic efficacy of the new
      drugs, safety considerations require additional clinical validation. Long-term
      outcomes and costs also need to be addressed objectively.

PMID- 9262117
TI  - Diseases of the pleura.

PMID- 9262118
TI  - Mechanisms of pleural liquid formation in pleural inflammation.
AB  - Inflammatory processes are a major cause of pleural effusion. Besides being
      important clinically for diagnosis and treatment of patients with pleural
      effusions, studies of inflammatory pleural effusions shed light on the mechanisms
      of pleural liquid formation and also on general mechanisms of inflammation. In
      this current review, we have chosen papers within the past year that highlight
      aspects of clinical and research interest concerning inflammation and
      inflammatory pleural effusions. In some studies, investigators have investigated
      basic mechanisms of the roles of cytokines and adhesion molecules in inflammatory
      cell recruitment and leakage of liquid. In other studies, clinicians have
      attempted to measure inflammatory markers as a means of diagnosis. In light of
      these studies, we discuss the current understanding of inflammatory pleural
      effusions and suggest future avenues for exploration.

PMID- 9262119
TI  - Hemothorax and chylothorax.
AB  - Hemothorax and chylothorax remain perplexing medical problems. The primary cause
      of hemothorax is trauma, whereas the primary cause of chylothorax is cancer. Most
      patients with hemothorax can be treated with chest tube drainage only. Early
      thoracotomy with thoracic duct ligation is recommended for patients with
      chylothorax when conservative treatment with chest tube drainage and
      hyperalimentation fails. Radiation therapy is the mainstay of treatment for
      chylothorax related to cancer. Video-assisted thoracoscopy may play an increasing
      role in the surgical treatment of both hemothorax and chylothorax.

PMID- 9262120
TI  - Pleural disease in patients with AIDS.
AB  - Patients infected with HIV are at risk of developing a variety of infectious and
      malignant pleuropulmonary disorders. The three most common causes of AIDS-related
      pleural effusions are parapneumonic effusions or empyemas, tuberculosis, and
      Kaposi's sarcoma. However, the relative frequency of these conditions varies from
      series to series as well as from one region of the world to another. Pneumocystis
      carinii is a common pulmonary pathogen in AIDS, but it is rarely the cause of a
      pleural effusion. By contrast, P. carinii infection is strongly associated with
      the occurrence of spontaneous pneumothoraces. Pleural complications in AIDS are
      often difficult to treat and contribute significantly to the high morbidity and
      mortality of the syndrome. Recent progress in antiretroviral therapy as well as
      improved supportive care should lead to better survival rates in AIDS in the near
      future. Unfortunately, this progress may be associated with a growing number of
      patients with AIDS-related diseases, including the pleural complications
      discussed here.

PMID- 9262121
TI  - Current trends in pleurodesis.
AB  - Pleurodesis is intended to prevent the accumulation of fluid or air in the
      pleural space by creating symphysis between the visceral and parietal pleura. The
      main indications for this procedure are malignant effusions and pneumothorax. A
      reexpandable lung and reasonably long expected survival are criteria that must be
      met before pleurodesis is attempted in a patient with malignant pleural effusion.
      A low pleural fluid pH (less than 7.20) is a good predictor for both the presence
      of a trapped lung and short expected survival. Talc appears to be the sclerosing
      agent of choice in cases of cancer, whereas video-assisted thoracic surgery
      techniques are preferable for the treatment of pneumothorax, especially in young
      patients. To improve results and prevent complications, application of the right
      technique is crucial, especially with regard to size of drainage and rate of
      suction. In addition, recent research suggests that prevention of a systemic
      activation of coagulation with prophylactic heparin should be taken into account
      in patients who are undergoing pleurodesis for palliative treatment of malignant
      effusion.

PMID- 9262122
TI  - Bibliography current world literature. Neoplasms of the lung.

PMID- 9262124
TI  - Bibliography current world literature. Diseases of the pleura.

PMID- 9262123
TI  - Bibliography current world literature. Disorders of pulmonary circulation.

PMID- 9262125
TI  - Linkage analysis between idiopathic generalized epilepsies and the GABA(A)
      receptor alpha5, beta3 and gamma3 subunit gene cluster on chromosome 15.
AB  - INTRODUCTION: We tested the hypothesis that genetic variants within the GABA(A)
      alpha5, beta3 and gamma3 subunit gene cluster on chromosome 15q11-q13 confer
      genetic susceptibility to common subtypes of idiopathic generalized epilepsy
      (IGE). MATERIAL AND METHODS: Ninety-four families were selected from IGE patients
      with either juvenile myoclonic epilepsy (JME), juvenile (JAE) or childhood
      absence epilepsy (CAE). Cosegregation was tested between dinucleotide
      polymorphisms associated with the human GABA(A) alpha5, beta3 and gamma3 subunit
      gene cluster and three different IGE trait models. RESULTS: Evidence against
      linkage to the GABA(A) alpha5, beta3 and gamma3 subunit gene cluster was found in
      the entire family set and subsets selected from either CAE or JAE. In 61 families
      of JME patients, a maximum lod score (Zmax=1.40 at Theta(max)=0.00) was obtained
      for a broad IGE spectrum ("idiopathic" generalized seizure or generalized spike
      and wave discharges in the electroencephalogram) assuming genetic heterogeneity
      (alpha=0.37; P=0.06) and an autosomal recessive mode of inheritance. CONCLUSION:
      The possible hint of linkage in families of JME patients emphasizes the need for
      further studies to determine whether a recessively inherited gene variant within
      the GABA(A) alpha5, beta3 and gamma3 subunit gene cluster contributes to the
      pathogenesis of "idiopathic" generalized seizures and associated EEG
      abnormalities in a proportion of families.

PMID- 9262126
TI  - A clinical trial of dextromethorphan in amyotrophic lateral sclerosis.
AB  - INTRODUCTION: Although the cause of amyotrophic lateral sclerosis (ALS) is
      unknown, excitotoxicity mediated by glutamate has been implicated.
      Dextromethorphan is a NMDA-glutamate receptor antagonist with neuroprotective
      properties. MATERIAL AND METHODS: The effect of treatment with dextromethorphan
      (150 mg daily) in ALS patients was evaluated in a randomized, double-blind,
      placebo-controlled study. Forty-five patients were included in the analysis.
      RESULTS: At the end of the treatment period, 12 months after randomization, 15
      patients (65%) in the placebo group and 12 patients (55 %) in the
      dextromethorphan group were still alive (log rank test, P=0.49). Rates of disease
      progression, as expressed by rates of decline in pulmonary function and in
      functional disability, were similar in both groups except for a significantly
      less pronounced rate of decline in the ability scores for the lower extremities
      in the dextromethorphan group. CONCLUSION: Treatment with a relatively low dose
      of dextromethorphan did not result in an improvement in 12-month survival in ALS.

PMID- 9262127
TI  - Pattern of motor neurone disease in eastern India.
AB  - A clinical study about the pattern of motor neurone disease in eastern India was
      carried out from July 1993 to June 1995 at Bangur Institute of Neurology,
      Calcutta and SSKM Hospital, Calcutta. A total of 110 cases were studied and they
      constituted 0.11% of all neurological cases seen in the general OPD. Of 110
      cases, amyotropic lateral sclerosis (ALS) constituted 43.6%, progressive muscular
      atrophy (PMA) 10.9%, post-polio progressive muscular atrophy (PPMA) 1.8%, spinal
      muscular atrophy (SMA) 20%, atypical form Madras pattern of MND (MMND) 0.9% and
      monomelic amyotrophy (MMA) 22.7% of cases. Disease is more common in males than
      females and average duration of symptoms before presentation varied from 1 to 12
      months. Most of the patients were either agricultural labourers or manual workers
      in ALS variety whereas MMA variety was evenly distributed in both hard labourers
      and sedentary workers. Most of the patients in MMA and SMA groups presented
      before 30 years of age whereas ALS and PMA group presented after 30 years. Trauma
      was the commonest antecedent event in ALS and MMA followed by electrocution in
      the same two groups. Family history was found to be absent in SMA group though
      the disease is considered as a hereditary one. Weakness of the limbs and wasting
      of the muscles were common presenting symptoms and signs. Bulbar symptoms and
      signs were found only in the ALS group. EMG showed neurogenic pattern and mixed
      pattern in most of the patients in all groups. Only a few patients showed
      myopathic pattern. Neuroimaging study helped in exclusion of compressive lesion
      excepting two cases of MMA where facetal hypertrophy was present. Monomelic
      amyotrophy, a special variety of motor neurone disease, is not rare in this part
      as compared to other parts of India and Asia.

PMID- 9262128
TI  - Serial Gadolinium-enhanced MRI in untreated patients with acute optic neuritis:
      implications for natural history.
AB  - INTRODUCTION: Serial brain MRIs with and without Gadolinium (Gd)-DTPA were
      performed in acute optic neuritis (ON). MATERIAL AND METHODS: Fifty-nine
      untreated patients (44 female) aged 20-57 years with ON underwent MRI median 16 d
      from onset of symptoms of ON and at 1 and 12 months follow-up. RESULTS: At onset
      of monosymptomatic ON (AMON), 13 of 40 (33%) patients had lesions on MRI without
      Gd-DTPA compared with 15 of 19 (79%) patients with ON as part of clinically
      definite multiple sclerosis (CDMS). An initially abnormal MRI never normalized,
      whereas 3 patients with AMON with initially normal MRI had lesions at follow-up.
      In AMON enhancing lesions were seen in 5% of patients at onset, in 12% after 1
      month, and in 11% after 12 months. The corresponding figures in CDMS were 21%,
      38%, and 33%. All enhancing lesions were also seen on MRI without Gd-DTPA. The
      number of lesions on MRI without Gd-DTPA increased significantly with time in the
      8 patients with AMON with enhancing lesions at one or more MRIs. New enhancing
      lesions appeared in 11 patients (6 AMON), of whom 3 (2 AMON) had an exacerbation.
      In contrast, 12 (5 AMON) patients had an exacerbation, being accompanied by new
      enhancing lesions in only 3 (2 AMON) patients. CONCLUSION: Gd-DTPA did not
      increase the sensitivity of MRI, which was significantly higher in CDMS than in
      AMON, but improved the understanding of the natural history of AMON and CDMS. The
      dynamics of enhancing lesions did not correlate well with exacerbations. Serial
      MRI and clinical assessment are supplementary in monitoring disease activity.

PMID- 9262129
TI  - Mitogenic response and steroid sensitivity in MS lymphocytes.
AB  - OBJECTIVES: We investigated mitogenic response and steroid sensitivity in
      multiple sclerosis (MS) lymphocytes to establish if MS lymphocytes were less
      steroid responsive. MATERIAL AND METHODS: We compared mitogenic response to
      phytohaemagglutinin (PHA) and inhibition by dexamethasone (DEX) in circulating
      lymphocytes from both MS patients and healthy subjects. RESULTS: We found a range
      of responses in each group but no significant differences between the two groups,
      nor in patients with and without enhancement on magnetic resonance imaging. The
      mid-inhibitory concentration of DEX in response to 1 microg/ml PHA was
      significantly lower than that for 2.5 microg/ml PHA in the patients. The mid
      inhibitory concentrations of DEX in response to 2.5 microg/ml PHA negatively
      correlated with endogenous serum cortisol concentrations. CONCLUSION: These data
      imply a spectrum of glucocorticoid response that is similar in normal and MS
      lymphocytes and can partly explain why response to steroid therapy is variable.

PMID- 9262130
TI  - Effects of MRI abnormalities on WAIS-R performance in solvent abusers.
AB  - OBJECTIVE: To clarify how chronic solvent abuse affects cognitive function using
      magnetic resonance imaging as an index of brain damage. MATERIAL AND METHODS: A
      total of 25 chronic solvent abusers underwent magnetic resonance imaging with
      quantitative neurometry and Wechsler Adult Intelligence Scales revised. RESULTS:
      The abusers with white matter change (n=10) showed significantly (P<0.05) lower
      performance IQ, especially in Digit Symbol subtest (P<0.01). Also, the severity
      of pontine atrophy was significantly correlated with PIQ (r=0.60, P<0.01).
      CONCLUSIONS: These data indicate that solvent abuse causes the decline in the
      test performance reflecting cognitive and fine motor dysfunction and that white
      matter changes and pontine atrophy may have some roles in this decline.

PMID- 9262131
TI  - Depression of neuromuscular transmission in methylmercury-poisoned rats: a glass
      microelectrode and single fiber electromyography study.
AB  - Changes in neuromuscular transmission were examined in methylmercury (MeHg)
      poisoned rats, given a total oral dose of 60 mg CH3HgCl at 5 mg/kg/day. A
      microelectrode study was done on the 21st day. The mean quantal content and mean
      values of the immediately available pool of ACh in the MeHg-poisoned rats were
      reduced as compared to those in the control rats, but the mean values for the
      release probability of ACh did not differ significantly. Stimulation single fiber
      electromyography (SFEMG) was done on the biceps femoris muscle at 1, 5, 10 and 20
      Hz on the 28th day. Both a significant and consistent increase in jitter were
      found at increasing stimulation rates in the MeHg-poisoned rats. The SFEMG
      findings suggest presynaptic involvement due to accelerated depletion of ACh. We
      confirmed that neuromuscular transmission is depressed in MeHg-poisoned rats in
      vivo and in vitro.

PMID- 9262132
TI  - Turn/amplitude-analysis in subclinical myogenic lesions.
AB  - OBJECTIVES: To investigate the accuracy of the turn/amplitude-analysis (TAA) in
      the detection of subclinical myogenic lesions, for which Duchenne (DMD) carriers
      were taken as a model. MATERIALS AND METHODS: Conventional EMG (MUAP analysis)
      and the TAA with/without force monitoring were applied to the right brachial
      biceps and femoral rectus muscles of 26 healthy subjects, 11 possible DMD
      carriers and 5 obligate DMD carriers. RESULTS: Conventional EMG was
      unspecifically abnormal in 4 possible and 2 obligate DMD carriers, neurogenic in
      1 possible DMD carrier and myogenic in none of the DMD carriers. Mean turns/s
      (T/S), amplitude/turn (A/T) and the ratio (T/S:A/T) were not significantly
      different between controls and possible or between controls and obligate DMD
      carriers. With force monitoring, the ratio (T/S:A/T) was myogenic in 1 obligate
      DMD carrier at 20% of maximum (brachial biceps). One possible DMD carrier showed
      a neurogenic distribution of the single T/S-A/T pairs around the normal cloud at
      60% of maximum (brachial biceps). Without force monitoring, the TAA was normal in
      all DMD carriers. CONCLUSIONS: TAA is of limited help in demonstrating
      subclinical myopathy, irrespective of whether it is carried out with or without
      force monitoring.

PMID- 9262133
TI  - Changes of sympatho-adrenal and hypothalamo-pituitary-adrenocortical system in
      patients with head injury.
AB  - To determine the role of the sympatho-adrenal (SAS) and hypothalamo-pituitary
      adrenocortical system (HPAS) after head injury, the relationship between venous
      blood epinephrine (E), norepinephrine (NE), adrenocorticotropic hormone (ACTH),
      cortisol levels, and clinical condition was examined in 55 patients. These
      observations suggest that head injury causes mainly activation of the above
      mentioned systems depending on the severity of trauma. An inverse correlation
      between the levels of E, NE and Glasgow Coma Scale score, indicating the severity
      of head injury was revealed. ACTH and cortisol were similarly related to the
      clinical condition, although the observed correlation was less expressed. The
      changes in hormonal levels were present during the whole research period (1
      week), although a certain shift to normalization was observed. However,
      catecholamines and ACTH levels in plasma were relatively low in severely head
      injured patients whose CT scans revealed serious alterations in the mesencephalic
      diencephalic area. At the same time their cortisol levels obtained maximal values
      and their chance to survive was diminutive. The results of this study indicate
      that investigation of hormones of SAS and HPAS might be useful as an additional
      method in the complex of ordinary examinations in establishing early prognosis in
      patients with brain injury.

PMID- 9262134
TI  - Paraparesis caused by a bilateral cervical synovial cyst.
AB  - We describe a 64-year-old man who suffered from rapidly progressive paraparesis.
      At operation the cervical cord of the patient was found to be displaced
      anteriorly due to compression caused by an epidural synovial cyst. The cyst was
      located bilaterally on the dorsolateral aspect of both CVII facet joints. The
      rapid development of paraparesis in this patient can, thus, be explained by the
      enlargement of the cyst on both sides of the spinal cord. After microsurgical
      removal of the cystic tumor, the recovery of the patient was good. Cervical
      epidural cysts are extremely rare, and only anecdotal cases have been reported in
      the literature. Among all previously described patients the present case is
      unique due to the bilateral location of the cyst.

PMID- 9262135
TI  - Auditory event related potentials in patients with epilepsy on sodium valproate
      monotherapy.
AB  - OBJECTIVES: The effects of antiepileptic drugs on event related potentials (ERPs)
      have been studied, but with contradictory results. In this study we examine the
      effect of sodium valproate (VPA) on ERPs in patients with epilepsy. MATERIALS AND
      METHODS: Auditory event related potentials were recorded in 40 patients with
      idiopathic generalized epilepsy, 20 on monotherapy with sodium valproate (VPA),
      20 on monotherapy with carbamazepine and 20 age and sex matched controls. All
      subjects performed a simple auditory discrimination task in which a target tone
      was presented on 20% of the trials. RESULTS: Mean P3 latency of the VPA group was
      significantly prolonged but not in carbamazepine group and healthy controls.
      CONCLUSION: We conclude that VPA monotherapy has an effect on P300 latency in
      patients with epilepsy. This difference might be attributed to effects of
      treatment with VPA and may clarify in the future the mechanism of P300.

PMID- 9262136
TI  - Development of flexible ventriculoscope (Yamadori-type VII) and its application
      to experimental animals.
AB  - We developed a new ventriculoscope (Yamadori-type VII), a 2.1 mm calibrated
      fiberscope with a monopolar coagulator, that can be inserted from the cisterna
      cerebellomedullaris into the third cerebral ventricle of experimental animals,
      like dogs. With the improved performance of the neuroendoscope compared to its
      prototype, Yamadori III, it was possible to inspect clearly and to produce
      electrocoagulative lesions accurately on any part of the intraventricular
      structures with minimal injury to nearby vital brain areas.

PMID- 9262137
TI  - A reliable system of ventricular coordinates for the cartography and stereotaxy
      of the amygdala (and anterior hippocampus) in macaques.
AB  - The most reliable stereotactic methods in primates resort to ventricular as
      opposed to bony landmarks. The usual CA-CP system did not appear satisfactory for
      stereotaxy of the amygdala and anterior hippocampus. Variation studies on
      ventriculograms and reconstructions from histological material were done to find
      more reliable systems. The most precise system of coordinates for cartography and
      stereotaxy of the amygdala is based on the 'amygdalar notch', a ventricular
      diverticulum forming the angle between the inferior and anterior borders of the
      temporal horn of the lateral ventricle, located beneath the inferior border of
      the amygdala. The AN point, the vertex of the notch in the sagittal direction, is
      a reliable ventricular landmark in the antero-posterior and infero-superior
      directions. The medial vertex of the diverticulum, ANm, is a ventricular landmark
      in the medio-lateral direction. The 'AN system of coordinates' is a reliable
      system for amygdalar stereotaxy. Stereotaxy of the anterior hippocampus would
      benefit from other ventricular landmarks. The most lateral point of the main body
      (HiL) is a landmark for the medio-lateral dimension. Ventriculography and
      ventricular landmarks should always be used for stereotaxy in primate species.

PMID- 9262138
TI  - Survival and differentiation of purified embryonic chick retinal ganglion cells
      cultured at low density in a chemically defined medium.
AB  - Both, a tailored chemically defined nutrient medium (BP5) and a sandwich culture
      sustain the survival for more than a week and allow the differentiation of
      embryonic chick retinal ganglion cells (RGCs) seeded at low density. Purification
      of RGCs from 7-11-day old embryos was accomplished by panning using specific anti
      chicken Thy-1 antibodies immobilized in plaques. Yield of RGCs was less than 1%
      of the calculated number of these cells in the used retinas. This result agrees
      with the scarce expression of Thy-1 in immature retina; accordingly, the most
      mature RGCs are those probably selected by the panning. This assumption obtained
      support on the expression of gangliotetraoxylgangliosides (GTOG), that
      characterize the differentiated retinal neurons. Thus, the outgrowth of processes
      observed in cultured cells, might imply axonal regeneration in mature neurons.
      This manageable RGC culture method approaches a system for studying the in vitro
      trophic factors and substrata which affect axonal regrowth in central nervous
      system cells.

PMID- 9262139
TI  - Measurement of intracellular Na+ concentration by a Na+-sensitive fluorescent
      dye, sodium-binding benzofuran isophthalate, in porcine adrenal chromaffin cells-
      usage of palytoxin as a Na+ ionophore.
AB  - Palytoxin was found to equilibrate sodium ions (Na+) across the cell membrane
      much faster than dose gramicidin, which has been frequently used to calibrate the
      intracellular Na+ concentration ([Na+]in), in cells treated with a Na+-sensitive
      fluorescent dye, sodium-binding benzofuran isophthalate (SBFI). Palytoxin was
      capable of equilibrating Na+ in cells treated with SBFI-acetoxymethyl ester (SBFI
      AM) and in voltage-clamped cells loaded with SBFI through a patch pipette.
      Nicotine caused a dose-dependent increase in ([Na+]in) in porcine adrenal
      chromaffin cells treated with SBFI-AM and caused a simultaneous increase in
      [Na+]in and inward current in the voltage-clamped cells loaded with SBFI.
      Palytoxin has an advantage of calibrating ([Na+]in) in a shorter time than dose
      gramicidin because of its powerful ionophoretic activity.

PMID- 9262140
TI  - Transfection of rat brain cells by electroporation.
AB  - Genetic intervention is a powerful means for answering basic biological questions
      about molecular events taking place in brain cells underlying complex behaviors.
      Traditional transfection method has proved difficult to apply to neuronal cells.
      We therefore described an alternative procedure for introducing DNA into cultured
      rat brain cells by electroporation. The various parameters involving the voltage,
      capacitance and electroporation buffer are investigated. We found that this
      transfection procedure is simple, reproducible and applicable to rat brain cells
      in vitro.

PMID- 9262141
TI  - Anatomical localization of electrophysiological recording sites by co-ordinate
      transformation.
AB  - A method for estimating the anatomical locations of the units recorded in
      electrophysiological mapping experiments is described. A total of three locations
      must be marked by dye injections or electrolytic lesions and identified in tissue
      sections. From those locations, equations are derived to translate, scale, and
      rotate the three-dimensional co-ordinates of the recording sites, so that they
      are correct for a second, three-dimensional co-ordinate system based on the
      anatomy of the mapped structure. There is no limit to the number of recording
      sites that can be localized. This differs from methods that require a dye
      injection or lesion to be made at the exact location at which a particular unit
      was recorded. The accuracy of the transformed co-ordinates is limited by the
      accuracy with which the co-ordinates can be measured: in test measurements and in
      the experiments for which this algorithm was developed, the computed co-ordinates
      were typically accurate to within 100 microns or less.

PMID- 9262142
TI  - Hippocampal lesions induced by ionizing radiation: a parametric study.
AB  - The selective lesion of granule cell populations in the dentate gyrus induced by
      ionizing radiation has been proposed as a useful method for evaluating the
      effects of hippocampal lesions on behavioral tasks. In the first part of the
      present study we confirmed the induction of the selective lesion of hippocampal
      dentate gyrus by ionizing radiation in infant Wistar rats, reported previously,
      but to a smaller extent with less cell loss. A parametric study was thus
      performed to assess the effect of modification of the parameters previously
      tested, comprising three further steps: an increase in the total dose of X-rays
      and modification of the fractionating schedule; use of three radiation types, X
      ray, gamma-ray, and electrons (at two energy levels, 3 and 7 mev); use of three X
      ray energy levels, 180, 200 and 250 kVp; and assessment of the effect of five
      total X-ray doses, at 200 kVp, 10, 14, 16, 18 and 20 gy (grays). The data
      suggests that X-ray radiation, in a total dose of 14 gy, at the 200 kVp energy
      level, fractionated into seven consecutive exposures of 2 gy each and produces a
      lesion of about 85% of the dentate gyrus granule cells.

PMID- 9262143
TI  - A low-cost method to analyse footprint patterns.
AB  - Neurological dysfunction can be assessed by analysing footprint patterns and
      walking tracks. However, because such an analysis is very time consuming, we
      developed an MS-Windows program called FOOTPRINTS which facilitates the analysis
      of the commonly used measures and which is considerably quicker than manual
      scoring methods. The prints are scanned at a resolution of 75 dpi and stored as
      black and white bitmaps for further analysis. In order to validate the program,
      we analysed the footprint patterns of mice and rats, using both the program and
      the conventional manual scoring method. In the first study, the walking patterns
      of 3-, 14-, and 26-month-old Janvier Wistar rats were compared, and in the second
      the footprint patterns of C57BL mice were assessed. Comparison of the data
      obtained using the program and of the data obtained by manual scoring showed that
      the computer-based analysis gives reliable results. The program saves
      considerable time as the analysis took 1/8th of the time needed for manual
      evaluation.

PMID- 9262144
TI  - An interface holding chamber for anatomical and physiological studies of living
      brain slices.
AB  - The popularity of infrared DIC videomicroscopy for a variety of anatomical and
      physiological studies in living brain slices has created a need for holding
      chambers to allow more than one slice to be examined during a single experiment.
      As is well known, the yield of experiments requiring living brain slices is
      severely limited by the conditions under which these slices are maintained prior
      to being examined. Previous electrophysiological and morphological studies have
      demonstrated that slices maintained submerged in solution deteriorate
      dramatically compared to those kept at the gas/fluid interface, even after only
      1.5 hours and many recording chambers incorporate the interface principle in
      their design. However, to our knowledge, as obvious as it may seem, this
      principle has not been applied to the design of holding chambers, and those which
      are in current use are of the non-optimal, submerged type. We have designed a
      simple, but extremely effective holding chamber for incubation of brain slices
      floating at the gas-fluid interface. The slices held in this chamber have been
      maintained for at least 12 hours in excellent condition as shown here by rich
      labeling of their local axonal arbors. In addition, the chamber is designed to
      hold individual slices (up to 1 cm2 in size) in separate compartments for better
      preservation of brain slices from valuable species (e.g. animals subjected to
      experimental treatments, nonhuman primates and human biopsy tissue).

PMID- 9262145
TI  - The novel use of vascular access ports for intravenous self-administration and
      blood withdrawal studies in squirrel monkeys.
AB  - An important experimental challenge in research with squirrel monkeys (Saimiri
      scureus) is the development of a reliable closed intravenous system for long term
      drug self-administration studies and the collection of multiple timed blood
      samples. A surgical procedure using a vascular access port (VAP) system was
      developed to provide easy access for venous samples or drug infusions. Daily
      experiments in chaired monkeys were simple and reliable for durations of up to 6
      h. The quantitative performance of the VAP system was evaluated by the number of
      days until port failure for self-administration studies and the number of days
      during which blood samples could be collected beyond an initial time of 91 days.
      The mean best performance for VAP system functional time for self-administration
      studies was 437 +/- 73 and the mean worst performance was 281 +/- 79. The mean
      best performance for blood withdrawal functional time was 362 +/- 81 and the mean
      worst performance was 332 +/- 85. The qualitative performance of the VAP system
      is described including complications that developed during the procedure;
      corresponding suggestions for corrective actions are discussed. Enhancements to
      increase port performance are also recommended.

PMID- 9262146
TI  - Short term storage of samples containing monoamines: ascorbic acid and
      glutathione give better protection against degradation than perchloric acid.
AB  - In order to study the protection of monoamines from degradation during short-time
      storage, the effect of three different antioxidants on the degradation of
      dopamine, dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5
      HIAA) was analyzed after 5 and 20 h. The results showed that dopamine was still
      quite stable after 20 h storage at room temperature, but that about 95% of 5-HIAA
      had disappeared. The best protection against degradation of all three substances
      was achieved when 15% v/v of a solution containing 1-2 mM ascorbic acid or 40 mM
      glutathione was added to the sample, resulting in near 100% protection after 20
      h. Perchloric acid actually accelerated the degradation of 5-HIAA.

PMID- 9262147
TI  - Induction and duration of long-term potentiation in the hippocampus of the freely
      moving mouse.
AB  - We describe a simple method, using readily available minaturised components, for
      inducing and monitoring long-term potentiation (LTP) at perforant path-granule
      cell synapses in the dentate gyrus of the freely moving mouse. Tetanic
      stimulation induced LTP of the field EPSP and the population spike which
      persisted for more than 24 h but was not present 10 days after the tetanus. The
      potentiation of the population spike was proportionately greater than the
      potentiation of the EPSP (E-S potentiation). Induction of LTP was blocked by
      intraperitoneal injections of the N-methyl-D-aspartate (NMDA) receptor
      antagonist, 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP).

PMID- 9262148
TI  - The shrinkage of the human brain stem during formalin fixation and embedding in
      paraffin.
AB  - On the basis of measurements on fresh human brains (n = 33), changes in size of
      the brain stem which occurred as a result of formalin fixation and embedding in
      paraffin were quantified and converted into linear correction factors. In
      contrast to the known changes in the cerebrum, the formalin fixation did not
      result in a 'positive formalin effect', but left transverse values unchanged and
      led to decreases in longitudinal distances of 1-8% (correction factors: 1.01
      1.09). Further embedding resulted in a linear shrinkage of 11-12% (correction
      factors: 1.12-1.13) transversely and 17% (correction factor: 1.21)
      longitudinally, which was smaller than the shrinkage in the cerebrum of 11-25%
      (correction factors: 1.13-1.34) reported in the literature. The examinations
      revealed changes in the brain stem caused by the total fixation and embedding
      process different from those of the cerebrum.

PMID- 9262150
TI  - Multi-channel metallic electrode for threshold stimulation of frog's retina.
AB  - A simple method for making a stimulating multi-channel metallic electrode is
      proposed. The method uses furnace-shaped multiple fine glass tubes as channel
      guides for inserted tungsten wires that are pulled as a unit to produce multi
      channel metallic electrode with a tapered tip. By shortening the tip, the desired
      inter-channels distances (from tens to hundreds of micrometers) can be
      established with a high degree of accuracy. Such an electrode was used to
      stimulate the layer of ganglion cells in a frog's retina. The responses to
      stimuli were recorded extracellularly in the contralateral tectum from the
      terminal arborizations of the excited ganglion cells' axons. A larger area of the
      retina may be excited when several channels are used as a cathode and several
      others as an anode. By varying the stimulating pairs of the channels it is
      possible to change the site of excitation without displacing the electrode.
      Separate ganglion cells may be stimulated, provided the appropriate pair of
      channels is selected. In this case 'all-or-none' responses to the threshold
      stimuli are obtained in the tectum. The artefact of the stimulus is diminished
      effectively by joining additional channels to the anodic one.

PMID- 9262149
TI  - Differentiated B104 neuroblastoma cells are a high-resolution assay for
      micropatterned substrates.
AB  - The B104 neuroblastoma cell line was investigated for use as an assay for
      predicting the patterning of primary neurons. B104 cells were grown on four
      uniform substrates with the result that the cells preferred, in descending order,
      poly-D-lysine (PDL), phenyltrichlorosilane (PTCS), coverslip glass, and silicon
      dioxide coated coverslips. B104 cells were then grown on micropatterned PDL grids
      on silicon dioxide coated substrates with excellent patterning. Compliance of
      somata to the pattern, defined as the percentage of cell bodies in a grid field
      located on the grid pattern, was 86% after 8 h. Neurites were not as compliant,
      since only 10% of background areas were free of neurites and connected cells.
      Compliance at longer time periods was greatly reduced. With the addition of the
      differentiating agent dibutyrylcyclicAMP (DBcAMP), the compliance of somata was
      maintained at high levels for up to 72 h. Also, the compliance of neurites
      greatly increased (70%) and showed positive improvement with longer pattern path
      lengths, contrary to B104 cells without DBcAMP. At longer times neurite
      compliance was reduced (12% at 28 h and 44% at 72 h). Although there are
      differences in substrate preferences, the B104 system with DBcAMP appears to be a
      useful tool in the investigation of the technology of patterned substrates.

PMID- 9262151
TI  - Temporal and spatial monitoring of exocytosis with native fluorescence imaging
      microscopy.
AB  - Exocytosis of rat peritoneal mast cells (RPMCs) was monitored temporally and
      spatially using native fluorescence imaging microscopy with 305-nm laser
      excitation. Real time chemical images of the relative amounts of serotonin and
      protein released from each cell are obtained. Individual cells released different
      amounts of material and the time delay of the release event after stimulation by
      polymyxin varied from cell to cell. Release consisted of a main burst of activity
      followed by slow sustained secretion over many seconds. The images show that
      different regions of a given cell behave asynchronously in releasing material
      into the surrounding medium. On rare occasions, highly localized fluorescence
      bursts can be seen in the vicinity of the cell. Presumably, these are due to
      delayed release of fluorescent mediators from single granules, following
      detachment of the latter from the cell. These quantitative fluorescence
      measurements allow one to follow the time-course of the physiologically important
      parameter---the amount of material that is secreted into the body fluid on
      stimulation.

PMID- 9262152
TI  - Demonstration of glutamate immunoreactivity in vagal sensory afferents in the
      nucleus tractus solitarius of the rat.
AB  - To investigate whether glutamate is a neurotransmitter in vagus nerve sensory
      afferents terminating in the nucleus tractus solitarius, these terminals were
      identified by the anterograde transport and their glutamate content examined
      using the post-embedding immunogold technique. After injection of horseradish
      peroxidase into the nodose ganglion anterogradely labelled axonal boutons were
      visualized throughout the nucleus of the solitary tract (nTS), the dorsal
      motonucleus of the vagus nerve (DVN), predominantly ipsilateral to the injection,
      and to a lesser extent in the area postrema. Electron microscopic analysis of 47
      anterogradely labelled boutons in the nTS following post-embedding
      immunocytochemistry for glutamate revealed that 43 of these boutons (> 91%)
      contained a level of glutamate immunoreactivity significantly greater (P <
      0.001%) than that observed in the surrounding tissue. The observed enrichment of
      glutamate immunoreactivity in boutons identified as vagus nerve sensory afferents
      indicate that glutamate may be a transmitter in these neurones.

PMID- 9262153
TI  - Behavioural performance in three substrains of mouse strain 129.
AB  - Recently, the possibility has been raised that the behavioural abnormalities seen
      in null-mutant mice might be determined by their genetic background rather than
      by loss of gene function, especially when the 129 mouse strain is used as
      supplier for embryonic stem (ES) cells. To examine this issue we tested three 129
      mouse substrains (129/J, 129/Ola, 129/Sv-ter/+) and C57BL/6 (B6) in the Morris
      water maze, the open field, the plus maze and two tests assessing motor co
      ordination. We identified only for the 129/J substrain substantial behavioural
      deficits. These mice are albinos and carry the pink-eyed dilution allele and
      differed in their basal anxiety level as assessed in the open-field test. They
      were severely impaired in spatial learning and memory (Morris water maze test),
      in the Porsolt swim test, which also measures learning and in motor co
      ordination. However, the 129/J substrain has not been used as ES cell donor in
      null-mutant mice where behavioural abnormalities were observed. Instead, mice
      from 129/Ola and 129/Sv-ter/+ substrains have been commonly used as suppliers for
      ES cells. These performed normally in most of the tests, including Morris water
      maze test.

PMID- 9262155
TI  - Source localization of the N400 response in a sentence-reading paradigm using
      evoked magnetic fields and magnetic resonance imaging.
AB  - The aim of the present investigation was to localize the sources of the N400
      response elicited in a sentence-reading paradigm. Eight neurologically healthy
      adults viewed sentences that were presented one word at a time in the center of a
      computer screen. Half of the sentences ended with a semantically inappropriate
      word, while the other half had appropriate endings. Event-related potentials
      recorded at Fz and Pz showed a negative-going deflection, the amplitude of which
      was strongly affected by semantic congruity (N400). Evoked magnetic fields that
      were simultaneously recorded over the left hemisphere showed clear magnetic field
      extrema in seven subjects during the time course of the N400. Underlying sources
      were successfully modeled as single equivalent current dipoles. Anatomical
      regions that contained the dipoles were localized by superimposing dipole
      coordinates onto magnetic resonance scans. Dipole regions were found in temporal
      lobe structures, in the vicinity of the hippocampus and the parahippocampal gyrus
      (in two subjects) and in posterior temporal neocortical regions (in the vicinity
      of the middle temporal gyrus; in five subjects). These findings are consistent
      with the view that posterior association cortices in the left hemisphere are
      involved in word recognition and semantic comprehension during reading.

PMID- 9262154
TI  - Excitation of type II anterior caudate neurons by stimulation of dopamine D3
      receptors.
AB  - Previous studies have demonstrated that both direct- and indirect-acting dopamine
      (DA) receptor agonists excite type II neurons in the anterior caudate (CN) by
      stimulation of DA receptors belonging to the D2 receptor subfamily (D2, D3, D4
      receptor subtypes). In the present study, pramipexole, a D3-preferring DA agonist
      effective in treating Parkinson's disease, excited type II anterior CN neurons.
      As with other direct-acting agonists, excitation of the CN neurons occurred only
      at doses above those that silenced DA neurons in the substantia nigra pars
      compacta (SNPC). Although more potent than pramipexole in inhibiting SNPC cells,
      PNU-91356A, a D2-preferring agonist, did not excite type II CN cells. The D3
      preferring antagonist (+)-AJ76 was weaker than haloperidol, a D2-preferring
      antagonist, in reversing the effects of amphetamine on firing rates in
      dopaminergic neurons in both the SNPC and the CN. However, in relationship to its
      potency in the SNPC, (+)-AJ76 was more potent than haloperidol in the CN. PNU
      101387, a selective D4 antagonist, did not alter amphetamine-induced stimulation
      of type II CN neurons. We conclude that DA agonists may excite type II anterior
      CN neurons via D3 receptor activation. The stimulation of these neurons may
      contribute to the anti-parkinsonian effects of pramipexole.

PMID- 9262156
TI  - Involvement of protein kinase C in homologous desensitization of histamine-evoked
      secretory responses in rat chromaffin cells.
AB  - The secretory responses in rat adrenal chromaffin cells to histamine H1 receptor
      stimulation desensitize during repetitive stimulation. The rate of development of
      this desensitization was slowed by Ro 31-8220, a protein kinase C (PKC)
      inhibitor. Ro 31-8220 also reversed part of the desensitization which had been
      induced by earlier histamine stimulation. Phorbol 12,13-dibutyrate (PDBu), an
      activator of protein kinase C, inhibited histamine-evoked catecholamine (CA)
      secretion almost completely. The inhibitory effect of PDBu on the H1-receptor
      mediated secretory response was antagonized by Ro 31-8220. Histamine induced
      [Ca2+]i increases due to Ca2+ entry and Ca2+ release from intracellular Ca2+
      stores in fura-2-loaded adrenal medullary cells. These [Ca2+]i increases were
      abolished in PDBu-treated cells. These results suggest that the activation of PKC
      following histamine H1 receptor stimulation plays a significant role in the
      process of homologous desensitization of histamine-evoked secretory responses in
      rat chromaffin cells, through modulation by PKC of H1 receptors and/or GTP
      binding proteins coupled with H1 receptors.

PMID- 9262157
TI  - Possible role of cytochrome P450 in inactivation of testosterone in immortalized
      hippocampal neurons.
AB  - The hippocampus as part of the limbic system is sensitive to gonadal hormones.
      The time-dependent expression of steroid receptors and the testosterone
      converting enzyme aromatase (CYP19) is well studied. In contrast, little is known
      about other cytochrome P450 enzymes in hippocampus which inactivate the gonadal
      hormones. For investigation of the total cytochrome P450 content and the
      expression of testosterone degrading CYP2B10 we used embryonic (E18) in
      comparison to postnatal (P21) immortalized hippocampal neurons. These embryonic
      neurons were demonstrated to react to hormones according a 'critical period' of
      sexual differentiation: testosterone treatment (1 microM to 5 microM in the
      culture medium) resulted in a decrease of beta-tubulin, as showed by
      immunocytochemistry and Western blotting. Measurements with reduced CO-difference
      spectrum elucidated that the P450 concentration in the embryonic neurons (10.2
      pmol/mg protein; S.D. +/- 1.9) was twice as high as in the postnatal ones (5.2
      pmol/mg protein; S.D. +/- 1.0). Correspondingly, a high value of the
      mitochondrial subfraction of approx. 141 pmol P450/mg protein was found in the
      embryonic neurons relative to the mitochondrial value of 37.7 pmol P450/mg
      protein in the postnatal neurons. Our results suggest a differential expression
      of cytochrome P450 during development. CYP2B10 was proved by electron microscopy
      and hormone degrading activity.

PMID- 9262158
TI  - Neurotrophin-4 (NT-4) and glial cell line-derived neurotrophic factor (GDNF)
      promote the survival of corticospinal motor neurons of neonatal rats in vitro.
AB  - We have used enriched dissociated, low density cultures of neonatal rat
      corticospinal motor neurons to evaluate the survival-promoting effect of nerve
      growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT
      3), neurotrophin-4 (NT-4), and glial cell line-derived neurotrophic factor (GDNF)
      and the ciliary neurotrophic factor (CNTF). Our current findings demonstrated
      that CNTF promoted the survival of corticospinal motor neurons, in the same
      fashion and at an equivalent potency, as was previously described using a
      different assay system. Among the other factors tested, we also found that NT-4
      and GDNF increased the number of surviving neurons in a dose-dependent manner,
      whereas NGF, BDNF and NT-3 showed no survival promoting effect on corticospinal
      motor neurons.

PMID- 9262159
TI  - Cardiovascular effects of microinjections of opioid agonists into the 'Depressor
      Region' of the ventrolateral periaqueductal gray region.
AB  - Microinjections of excitatory amino acids made into the ventrolateral midbrain
      periaqueductal gray of the rat have revealed that neurons in this region
      integrate a reaction characterised by quiescence, hyporeactivity, hypotension and
      bradycardia. Microinjections of both excitatory amino acids and opioids into the
      ventrolateral periaqueductal gray have shown also that it is a key central site
      mediating analgesia. The effects of injections of opioids into the ventrolateral
      periaqueductal gray on arterial pressure and heart rate or behaviour are unknown.
      In this study we first mapped in the rat the extent of the ventrolateral
      periaqueductal gray hypotensive region as revealed by microinjections of
      excitatory amino acids. We found that ventrolateral periaqueductal gray depressor
      region extended more rostrally than previously thought into the tegmentum
      ventrolateral to the periaqueductal gray. Subsequently we studied for the first
      time, the effects of microinjections of mu-, delta-, and kappa-opioid agonists
      made into the ventrolateral periaqueductal grey depressor region. In contrast to
      the effects of excitatory amino acid injections, microinjections of the mu-opioid
      agonist ([D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin) evoked hypertension and
      tachycardia at approximately 50% of sites. Similar to excitatory amino acid
      injections, microinjections of both the delta-opioid agonist ([D-Pen2,D
      Pen5]enkephalin), and the kappa-opioid agonist ((5,7,8)-(+)-N-Methyl-N-[7-(1
      pyrrolidinyl)-1-oxaspiro[4.5]dec-8-y l]-benzeneacetamide) evoked either a
      hypotension and bradycardia, or had no effect. These results indicate that
      different opiate receptor subtypes are present on a distinct population of
      ventrolateral periaqueductal gray neurons, or at different ventrolateral
      periaqueductal gray synaptic locations (pre- or post-synaptic).

PMID- 9262160
TI  - Changes in extracellular nitrite and nitrate levels after inhibition of glial
      metabolism with fluorocitrate.
AB  - The role of glial cells in nitric oxide production in the cerebellum of conscious
      rats was investigated with a glial selective metabolic inhibitor, fluorocitrate.
      The levels of nitric oxide metabolites (nitrite plus nitrate) in the dialysate
      following in vivo microdialysis progressively increased to more than 2-fold the
      basal levels during a 2-h infusion of fluorocitrate (1 mM), and the increase
      persisted for more than 2 h after the treatment. Pretreatment with N(G)-nitro-L
      arginine methyl ester attenuated the fluorocitrate-induced increase in nitric
      oxide metabolite levels. None of the glutamate receptor antagonists, including D(
      )-2-amino-5-phosphonopentanoic acid, 6,7-dinitroquinoxaline-2,3-dione, and (+/-)
      alpha-methyl-4-carboxyphenylglycine, inhibited the fluorocitrate-induced
      increase. The L-arginine-induced increase was significantly reduced by
      fluorocitrate treatment, while N-methyl-D-aspartate, (+)-alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid, and trans-(+/-)-1-amino-(1S,3R)-cyclopentane
      dicarboxylic acid increased nitric oxide metabolites levels in the fluorocitrate
      treated rats, as much as in control animals. These results suggest that glial
      cells play an important role in modulating nitric oxide production in the
      cerebellum by regulating L-arginine availability.

PMID- 9262161
TI  - Neurotoxicity in organotypic hippocampal slices mediated by adenosine analogues
      and nitric oxide.
AB  - Adenosine (ADO) and nitric oxide (NO) have been implicated in a variety of
      neurophysiological actions, including induction of long-term potentiation,
      regulation of cerebral blood flow, and neurotoxicity/neuroprotection. ADO has
      been shown to promote NO release from astrocytes by a direct effect on A1 and A2
      receptors, thus providing a link between actions of NO and adenosine in the
      brain. However, while adenosine acts as an endogenous neuroprotectant, NO is
      believed to be the effector of glutamate neurotoxicity. To resolve this apparent
      paradox, we have further investigated the effects of adenosine and NO on neuronal
      viability in cultured organotypic hippocampal slices exposed to sub-lethal (20')
      in vitro ischemia. Up to a concentration of 500 microM ADO did not cause toxicity
      while exposures to 100 microM of the stable ADO analogue chloroadenosine (CADO)
      caused widespread neuronal damage when paired to anoxia/hypoglycemia. CADO
      effects were significantly prevented by the ADO receptor antagonist theophylline
      and blockade of NO production by L-NA (100 microM). Moreover, CADO effects were
      mimicked by the NO donor SIN-1 (100 microM). Application of 100 microM ADO
      following blockade of adenosine deaminase (with 10 microM EHNA) replicated the
      effects of CADO. CADO, ADO + EHNA but not ADO alone caused a prolonged and
      sustained release of nitric oxide as measured by direct amperometric detection.
      We conclude that at high concentrations and/or following blockade of its
      enzymatic catabolism, ADO may cause neurotoxicity by triggering NO release from
      astrocytes. These results demonstrate for the first time that activation of
      pathways other than those involving neuronal glutamate receptors can trigger NO
      mediated neuronal cell death in the hippocampus.

PMID- 9262162
TI  - Detection and discrimination of propionic acid after removal of its 2-DG
      identified major focus in the olfactory bulb: a psychophysical analysis.
AB  - Prior 2-deoxyglucose and c-fos studies have demonstrated increased metabolic
      activity in a rostral dorsomedial area of the olfactory bulb in response to the
      vapor of propionic acid. We used psychophysical tests to assess the effect of
      removing this area of the bulb on odor sensitivity and discrimination. Normal
      rats, those with lesions of the rostral dorsomedial bulb or with control lesions
      of the lateral olfactory bulb were tested for propionic acid absolute detection
      and intensity difference thresholds and ability to discriminate propionic acid
      from other odors. There were no differences among groups for absolute or
      intensity difference threshold or on simple 2-odor discrimination tests but both
      groups with bulbar lesions made more errors than controls on a relatively
      difficult odor-mixture task. The results demonstrate that removal of an area of
      the bulb identified as responsive to propionic acid is essentially without effect
      on sensitivity to that odor or ability to discriminate it from other odors.

PMID- 9262163
TI  - Anoxia-induced depolarization in CA1 hippocampal neurons: role of Na+-dependent
      mechanisms.
AB  - We have previously shown that (1) removal of extracellular sodium (Na+) reduces
      the anoxia-induced depolarization in neurons in brain-slice preparations and (2)
      amiloride, which blocks Na+-dependent exchangers, prevents anoxic injury in
      cultured neocortical neurons. Since anoxia-induced depolarization has been linked
      to neuronal injury, we have examined in this study the role of Na+-dependent
      exchangers and voltage-gated Na+ channels in the maintenance of membrane
      properties of CA1 neurons at rest and during acute hypoxia. We recorded
      intracellularly from CA1 neurons in hippocampal slices, monitored Vm and measured
      input resistance (Rm) with periodic injections of negative current. We found that
      tetrodotoxin (TTX, 1 microM) hyperpolarized CA1 neurons at rest and significantly
      attenuated both the rate of depolarization (delta Vm/dt) and the rate of decline
      of Rm (delta Rm/dt) by about 60% during the early phase of hypoxia. The effect of
      TTX was dose-dependent. Amiloride (1 mM) decreased Vm and increased Rm in the
      resting condition but changed little the effect of hypoxia on neuronal function.
      Benzamil and 5-(N-ethyl-N-isopropyl)-2',4'-amiloride (EIPA), two specific
      inhibitors of Na+ dependent exchangers, were similar to amiloride in their
      effect. We conclude that neuronal membrane properties are better maintained
      during anoxia by reducing the activity of TTX-sensitive channels and not by the
      action of Na+-dependent exchangers.

PMID- 9262164
TI  - Preferential expression of kin, a nuclear protein binding to curved DNA, in the
      neurons of the adult rat.
AB  - The KIN17 gene product has been identified by cross immunoreactivity with anti
      RecA antibodies and by DNA recombination techniques, and is probably part of the
      DNA recombination-repair machinery. Following Western blotting and
      immunocytochemistry using anti-RecA antibodies, and in situ hybridization with
      specific KIN17 cDNA probes, we here report the detection of high levels of KIN
      protein and KIN17 mRNA in the CNS of adult rats. The RecA cross-reacting protein
      has an apparent molecular weight of 41 kDa and is located in the nucleus of brain
      cells. Both the KIN17 transcript and the protein were found to be widespread, but
      they were present in different proportions, depending on the type of brain cells.
      High levels of KIN protein were seen in neurons of the motor nuclei of the
      brainstem, the locus coeruleus, hippocampal formation, entorhinal cortex,
      Purkinje cells, pyramidal cells of the cortex and mitral cells. In contrast,
      using a combination of KIN17 mRNA in situ hybridization and GFAP
      immunocytochemistry (a marker of glial cells) showed that the KIN17 messenger is
      preferentially transcribed in neurons, the post-mitotic and long lived brain
      cells. We postulate that KIN17 play a role in the illegitimate recombination of
      DNA sequences and/or the repair of alterations of the genome in neurons.

PMID- 9262165
TI  - Forebrain metabolic activation induced by the repetition of audiogenic seizures
      in Wistar rats.
AB  - In Wistar rats susceptible to audiogenic seizures (Wistar AS) inbred in our
      laboratory, the exposure to an intense sound induces an epileptic seizure
      characterized by a running episode followed by a tonic phase showing the major
      involvement of brainstem structures. After 10-20 sound-induced seizures,
      development of facial and forelimb clonus and/or tonic-clonic seizures
      characterize the generalization from brainstem to the forebrain as a result of
      seizure repetition. In order to specify the anatomical substrates of repeated
      audiogenic seizures in Wistar AS, we used the 2-deoxyglucose (2DG) technique over
      a 5 min period to map the midbrain and forebrain structures activated by
      audiogenic seizures before and after seizure repetition. In naive Wistar AS, six
      of the 22 structures showed a significant 20-56% increase in relative optical
      densities compared to non-epileptic controls; these were central and medial
      amygdala nuclei, perirhinal cortex, medial septum, subthalamic and caudate
      nuclei. In kindled Wistar AS, 12 additional structures showed a significant 16
      121% increase in 2DG labeling. These structures were the substantia nigra, all
      layers of the hippocampus, the basolateral amygdala, three thalamic nuclei, the
      frontal motor and prefrontal cortices. In conclusion, the metabolic activation of
      midbrain and forebrain areas in kindled versus naive Wistar AS rats reflects the
      changes in the nature of the seizures and the involvement of these structures in
      the spread of seizure activity from the brainstem to the forebrain during seizure
      repetition.

PMID- 9262166
TI  - Both high- and low voltage-activated calcium currents contribute to the light
      evoked responses of luminosity horizontal cells in the Xenopus retina.
AB  - We examined the contribution of two intrinsic voltage-dependent calcium channels
      to the light-evoked responses of a non-spiking retinal neuron, the horizontal
      cell (HC). HC's isolated from the Xenopus retina were studied by the whole cell
      version of the patch clamp. In a mixture of agents which suppressed Na- and K
      dependent currents, we identified a transient, low voltage-activated Ca current
      suppressed by Ba2+ and blocked by Ni2+ (T-type) and a sustained, high voltage
      activated, dihydropyridine-sensitive Ca current that was enhanced by Ba2+ (L
      type). We made simultaneous intracellular recordings from rods and HC's in the
      intact, dark-adapted Xenopus retina. Under certain stimulus conditions, transient
      oscillations appeared in HC responses but were absent in rod light-evoked
      waveforms. One type of transient was seen at relatively hyperpolarized potentials
      (< -45 mV), was enhanced by Sr2+ and inhibited by Ni2+. It thus appears to depend
      on a T-type Ca-current. A second type of oscillation was seen to be superimposed
      on a prolonged depolarizing wave following light off in the HC and as spike-like
      depolarizations in rods. These oscillations were enhanced by Ba2+ and Sr2+, but
      blocked by the dihydropyridine, nifedipine, indicating their dependence on an L
      type calcium conductance. All calcium-dependent oscillations were suppressed by
      0.05-0.5 mM Co2+. Suppression of glutamate neurotransmission with CNQX or
      kynurenate, or glycine neurotransmission with strychnine, enhanced the HC
      oscillations.

PMID- 9262167
TI  - Continuous neurogenesis in the olfactory brain of adult shore crabs, Carcinus
      maenas.
AB  - To scrutinize the common belief that the number of neurons in the CNS of adult
      decapod crustaceans stays constant, in spite of their dramatic postlarval
      increase in size, I counted olfactory projection neurons (OPNs) in the brains of
      differently-sized postlarval shore crabs, Carcinus maenas, and performed in vivo
      labeling of proliferating cells with 5-bromo-2'-deoxyuridine (BrdU) on brains of
      adults. The number of OPNs increases continuously throughout the postlarval life
      of shore crabs and approximately doubles from the very young to the oldest
      animals. Brain sections from adult crabs labeled with BrdU revealed ongoing
      proliferation of cells in the lateral soma cluster, which consists of OPN cell
      bodies, and in the cluster of somata of hemiellipsoid body local interneurons,
      which are the targets of the OPNs. Post-injection survival times from 5.5 to 120
      h revealed a small but relatively constant number of labeled nuclei with neuronal
      morphology in both soma clusters of all specimens (31.3 +/- 9.5 S.D. nuclei per
      lateral cluster, n = 29; 20.1 +/- 4.5 S.D. nuclei per hemiellipsoid body cluster,
      n = 10). The labeled nuclei were located in a distinct proliferative zone in each
      cluster. There were significantly more labeled nuclei in both soma clusters after
      a prolonged post-injection survival time of 1 month (71.3 +/- 7.8 S.D. nuclei per
      lateral cluster, n = 4; 38.2 +/- 7.1 nuclei per hemiellipsoid body cluster, n =
      6). In both soma clusters the labeled nuclei formed a compact group that was
      dislocated from the proliferation zone towards the outer edge of the cluster. In
      the proliferation zone of the lateral cluster histological stainings revealed
      cell bodies of typical neuronal shape that are slightly smaller and more
      intensely stained than the surrounding OPN somata. Some of these cell bodies were
      captured in various stages of mitosis. Collectively, these data indicate that
      continuous neurogenesis occurs in the central olfactory pathway of the brain of
      shore crabs throughout their entire adult life. This unexpected structural
      plasticity may enable long-lived decapod crustaceans to adapt to ever-changing
      olfactory environments.

PMID- 9262168
TI  - Superoxide free radical and intracellular calcium mediate A beta(1-42) induced
      endothelial toxicity.
AB  - The 39-42 amino acid residue amyloid beta peptide (A beta), the major protein
      component in senile plaques and cerebrovascular amyloidosis in the brain in
      Alzheimer's disease (AD), has been shown to be neurotoxic in vitro. Accumulating
      data from several areas suggest that cerebrovascular dysfunction and damage may
      also play a significant role in the AD process. For instance, we have recently
      demonstrated enhanced vasoconstriction and resistance to relaxation in intact rat
      aorta treated with A beta [Thomas et al., beta-Amyloid-mediated vasoactivity and
      vascular endothelial damage, Nature, 380 (1996) 168-171]. Significant vessel
      damage occurred after thirty minutes of exposure, but could be prevented with
      superoxide dismutase. To further investigate the role of A beta toxicity on
      endothelial cells, we have applied A beta peptides to cultures of human aortic
      endothelial cells (HAEC). Our results show that both A beta(1-42) and A beta(25
      35) are toxic to HAEC in a time- and dose-dependent manner, and that this
      toxicity can be partially prevented by the calcium channel blocker, verapamil,
      and the antioxidant, superoxide dismutase. The common form of A beta, A beta(1
      40), which has been shown to be neurotoxic, is much less toxic to HAEC. A beta
      toxicity to HAEC occurs within 30 min of treatment with relatively lower doses
      than those usually observed in primary cultured neurons and vascular smooth
      muscle cells. It was recently reported that a variety of mutations in the beta
      amyloid protein precursor gene and the Presenilin-1 and -2 genes linked to early
      onset familial AD cause an increase in the plasma concentration of A beta(1-42)
      in mutation carriers [Scheuner et al., Secreted amyloid beta-protein similar to
      that in the senile plaques of Alzheimer's disease is increased in vitro by the
      presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease,
      Nature Med., 2 (1996) 864-870]. Human aortic endothelial cells are more sensitive
      to A beta(1-42) than A beta(1-40), via a pathway involving an excess of
      superoxide free radicals and influx of extracellular calcium. Finally, we have
      evidence that both apoptotic and necrotic processes are activated by the A beta
      peptides in these endothelial cells.

PMID- 9262169
TI  - A1 and A2A adenosine receptors and A1 mRNA in mouse brain: effect of long-term
      caffeine treatment.
AB  - The effect of oral treatment with caffeine, in doses that are known to produce
      marked adaptive effects, was investigated on A1 and A2A receptors in the mouse
      brain. Caffeine (0.1, 0.3 or 1 g/l) was added to the drinking water and the
      animals were sacrificed after a 14-day treatment period. Ligand binding to A1
      receptors was studied, using quantitative autoradiography, with the agonist
      [3H]cyclohexyladenosine (CHA) and the antagonist [3H]1,3-dipropyl-8-cyclopentyl
      xanthine (DPCPX). Caffeine did not remain in the sections during the
      autoradiography experiments. Caffeine treatment (1 g/l, but not 0.1 or 0.3 g/l)
      tended to increase [3H]CHA binding to the CA3 subfield of the hippocampus, but in
      no other region studied. There was no change in the number of A1 receptors since
      [3H]DPCPX binding to the CA3, cerebral and cerebellar cortex was not influenced
      by caffeine treatment. There was similarly no change in the ability of CHA to
      displace [3H]DPCPX binding, suggesting that there are no major changes in the
      proportion of A1 receptors that are coupled to G-proteins. mRNA for the A1
      receptor, measured by in situ hybridization, did not differ significantly between
      caffeine-treated and control mice in the structures examined. Thus, higher doses
      of caffeine can cause an increase in A1 agonist binding without a corresponding
      change in A1 mRNA or in A1 antagonist binding, suggesting that the adaptive
      changes seen upon prolonged caffeine treatment may be in sites different from A1
      receptors. Caffeine (1 g/l) increased A2A receptors in the striatum measured as
      binding of the agonist [3H]CGS 21680 suggesting that up-regulation of A2A
      receptors may be an adaptive effect of caffeine intake.

PMID- 9262170
TI  - Cloning and expression of the neuromedin B receptor and the third subtype of
      bombesin receptor genes in the mouse.
AB  - We cloned the genes for the mouse homologue of the neuromedin B receptor (NMB-R)
      and the bombesin receptor subtype 3 (BRS-3). Both receptor genes consist of three
      exons with well-conserved intron-exon borders. Although the NMB-R gene spans more
      than 10 kb, the BRS-3 gene spans only about 4 kb. Comparison of the mouse and
      human receptor sequences indicates 90% (NMB-R) and 85% (BRS-3) sequence homology
      at the amino-acid level. In the adult mouse, the NMB-R mRNA is expressed in the
      brain, testis, esophagus, intestine and uterus, whereas the BRS-3 mRNA is
      expressed predominantly in the brain. In the brain, the NMB-R gene expression is
      prominent in the thalamic and olfactory regions, and the BRS-3 gene is expressed
      particularly in the hypothalamic region. In mouse testis, the NMB-R gene
      expression is prominent, and the expression of BRS-3 mRNA is barely detected. In
      contrast, BRS-3 has been shown to be expressed in rat testis and guinea-pig
      uterus, therefore it is possible that a different subtype of the bombesin
      receptor mediates the same response in different species. Together with the mouse
      GRP-R gene cloned previously, cloning of the mouse NMB-R and BRS-3 genes permits
      comparison of function and structure of the three bombesin receptor subtypes in
      the mouse.

PMID- 9262171
TI  - Effects of pro-inflammatory cytokines in experimental spinal cord injury.
AB  - Following injury to the spinal cord, secondary tissue damage leading to massive
      additional tissue loss and inflammatory reactions as well as scar formation takes
      place. The precise functions and effects of the inflammatory cells and their
      secreted factors are largely unclear. The present study investigates whether the
      exogenous local administration of pro-inflammatory cytokines to mice after spinal
      cord injury can influence these intrinsic processes. A mixture of murine
      recombinant interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumour
      necrosis factor alpha (TNF alpha) was administered to the lesioned spinal cord of
      adult mice. These cytokines provoked an increased recruitment and activation of
      macrophages and microglial cells in the lesion area when administered 1 day post
      lesion. In contrast, when administered 4 days after the lesion, recruitment of
      macrophages was slightly increased while activation of microglia was decreased as
      compared to controls. The amount of tissue loss 7 days after trauma was smaller
      in the animals receiving the cytokine mixture than in the mice receiving Ringer
      control solution on day 4 after lesion. Thus the role of the inflammatory
      response in spinal cord injury seems to be complex and well regulated. Anti
      inflammatory cytokines and factors probably also contribute to the outcome of the
      damage following injury to the spinal cord.

PMID- 9262172
TI  - Comparative effects of a melatonin agonist on the circadian system in mice and
      Syrian hamsters.
AB  - S-20098 has potent and specific agonist properties on melatonin receptors both in
      vitro and in vivo. Behavioral studies on rodents already showed that repeated
      intraperitoneal administration of S-20098 could dose-dependently alter the
      functioning of the circadian clock. To determine whether single administration of
      S-20098 could alter the circadian rhythms of rodents, we first used the phase
      response curve (PRC) approach in two different species: Syrian hamsters and mice
      (C3H/HeJ). Our results show that the shape, circadian times and extent of the PRC
      to S-20098 look very similar in mice and hamsters. In both species, the phase
      advance portion of the PRC to S-20098 is limited to a 3 h window preceding the
      onset of locomotor activity, but the magnitude of phase shifts is larger in mice.
      We also tested the phase shifting effects of increasing doses of S-20098 during
      the interval of maximal sensitivity to this compound. Treatment with S-20098
      induces dose-dependent phase shifts, with maximal shifts observed after
      injections of 20 and 25 mg/kg S-20098 i.p., respectively, in mice and hamsters.
      Those results are in agreement with the limited distribution of melatonin-binding
      sites within the circadian clock of adult Syrian hamsters, as compared to other
      rodents.

PMID- 9262173
TI  - Hippocampally dependent and independent chronic spatial navigational deficits
      following parasagittal fluid percussion brain injury in the rat.
AB  - Previous reports have documented spatial navigational deficits following
      experimental traumatic brain injury (TBI), although the majority of the work to
      date has involved assessment at acute intervals following TBI, and has focused on
      tasks sensitive to hippocampal dysfunction. The present experiments were designed
      to investigate the chronic consequences of TBI, and the possible contribution of
      extrahippocampal dysfunction to TBI-induced spatial navigational deficits, in a
      moderate parasagittal fluid percussion TBI model. In Experiment 1, animals were
      pre-trained in a water maze, subjected to TBI or sham procedures, and re
      evaluated in the water maze 48 h following the insult. Six to 8 weeks following
      TBI, the same animals were required to navigate to a different platform location.
      TBI animals exhibited significant deficits in retention of previously learned
      spatial information at the 48 h interval, and marginally impaired acquisition of
      a novel platform location during the chronic test sessions. In Experiment 2,
      animals were required to navigate to novel spatial locations using cued (to
      evaluate extrahippocampal function) as well as non-cued variants of the water
      maze task during the 8 week period following the insult. Injured animals
      exhibited deficits in both tasks which gradually diminished over the course of
      testing. The results of these experiments indicate that moderate TBI is
      accompanied by both retention and acquisition deficits, and that some of the
      navigational deficits observed in the water maze can be attributed to
      extrahippocampal damage. The possible recovery of spatial navigational ability
      following parasagittal TBI at moderate intensities is also discussed.

PMID- 9262174
TI  - Beneficial effects of TDN-345, a novel Ca2+ antagonist, on ischemic brain injury
      and cerebral glucose metabolism in experimental animal models with
      cerebrovascular lesions.
AB  - The effects of TDN-345 on mortality and ischemic neurological deficit following
      transient global cerebral ischemia in Mongolian gerbils and also the rate of
      local cerebral glucose utilization (LCGU) in stroke-prone spontaneously
      hypertensive rats (SHRSP) with cerebrovascular lesions were investigated. In
      Mongolian gerbils, ischemia was produced by clamping the bilateral common carotid
      arteries for 15 min. TDN-345 (0.1-1.0 mg/kg) dose-dependently decreased the
      mortality and ischemic neurological deficit score when administered orally twice,
      60 min before ischemia and 90 min after recirculation. Additionally, TDN-345 (0.2
      or 1.0 mg/kg, p.o. once daily for 3 weeks after the onset of stroke) decreased
      the mortality and recurrence of stroke in SHRSP. To determine the site of action
      of TDN-345 in the brain, the rate of LCGU in various brain regions in SHRSP with
      stroke was examined using a [14C]2-deoxy-D-glucose method. The rate of LCGU
      decreased significantly in all the brain regions in SHRSP with stroke compared
      with Wistar-Kyoto (WKY) control rats, whereas the reduction in the rate of LCGU
      in SHRSP with stroke was prevented by TDN-345 treatment, especially in the
      sensorimotor cortex and locus coeruleus. These results suggest that TDN-345 has
      therapeutic efficacy in the treatment of cerebrovascular disease.

PMID- 9262176
TI  - Effect of chronic clozapine administration on [3H]MK801-binding sites in the rat
      brain: a side-preference action in cortical areas.
AB  - We studied modifications in [3H]MK801-binding sites in the rat brain after
      chronic clozapine. We found a 20-30% reduction of [3H]MK801-binding sites in the
      anterior cingulate, frontoparietal motor and frontoparietal somatosensory
      cortices on the left side but none on the right. We also demonstrated a 20%
      bilateral increase of N-methyl-D-aspartate (NMDA) receptors in the dentate gyrus
      of the hippocampus. No changes were found in the prefrontal cortex, caudate
      putamen, nucleus accumbens, hippocampus or olfactory tubercle.

PMID- 9262175
TI  - Differential effects of 5-HT3 receptor antagonism on working memory failure due
      to deficiency of hippocampal cholinergic and glutamatergic transmission in rats.
AB  - The muscarinic acetylcholine receptor antagonist scopolamine significantly
      increased the number of errors (attempts to pass through two incorrect panels of
      the three panel-gates at four choice points) in the working memory task with a
      three-panel runway setup, when injected bilaterally at 3.2 microg/side into the
      dorsal hippocampus. Concurrent infusion of the selective and potent 5
      hydroxytryptamine3 (5-HT3) receptor antagonist Y-25130 (0.32 and 1.0 microg/side)
      significantly attenuated the increase in working memory errors induced by
      intrahippocampal 3.2 microg/side scopolamine. Intrahippocampal Y-25130 (1.0
      microg/side) by itself did not affect working memory errors. On the other hand,
      intrahippocampal administration of the competitive NMDA receptor antagonist (+/-)
      3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) at 32 ng/side caused a
      significant increase in the number of working memory errors. However, Y-25130 at
      1.0 microg/side did not affect the increase in working memory errors when infused
      intrahippocampally together with 32 ng/side CPP. These results suggest that
      antagonism of hippocampal 5-HT3 receptors is ineffective against working memory
      failure resulting from blockade of NMDA receptor-mediated neurotransmission, but
      that it can compensate deficiency of septohippocampal cholinergic activity
      involved in working memory function of rats.

PMID- 9262177
TI  - Central acetylcholine synthesis and catabolism activities in the cuttlefish
      during aging.
AB  - Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities,
      measured in 10 central regions of young, middle-aged and old cuttlefish, showed a
      regional heterogeneity but with different age-related distribution patterns.
      Maximal acetylcholine synthesis and catabolism were observed in the inferior
      frontal and the optic lobes. Important age-related decreases in ChAT activities
      were evidenced in most regions, while only moderate variations were found for
      AChE. Since the superior frontal lobe is involved in visual learning, the
      dramatic decrease in ChAT activity observed in this lobe (-77%) could be
      implicated in the learning deficits reported in senescent Sepia.

PMID- 9262178
TI  - Behaviors and neurodegeneration induced by two blockers of K+ channels, the mast
      cell degranulating peptide and Dendrotoxin I.
AB  - Both the Mast Cell Degranulating (MCD) peptide and Dendrotoxin I (DTX(I)), two
      blockers of fast activation and slowly inactivating K+ channels, induced
      epileptiform seizures and brain damage after intracerebroventricular injection
      (200 pmol) in Sprague-Dawley rats. A considerable variation in the response of
      the rats was observed for each toxin. The neurodegeneration included the
      hippocampal formation, subiculum, septum, amygdala, and the cerebellum for both
      toxins, and the neocortex and anterior thalamic nuclei exclusively for DTX(I)
      treatment.

PMID- 9262179
TI  - Classification of dorsal horn neurons based on somatic receptive fields in cats
      with intact and transected spinal cords: neural plasticity.
AB  - Classification of dorsal horn neurons based on cell activity responses to somatic
      receptive fields stimulation, was compared between anesthetized cats with
      transected or intact cords. Results showed a significant (P < or = 0.001)
      difference. In animals with transected cords, dorsal horn neurons responded with
      less specificity to noxious and innocuous stimulation. The results are consistent
      with the proposition that loss of supraspinal influences plays a significant role
      in determining response characteristics of dorsal horn neurons.

PMID- 9262180
TI  - Increased number of unmyelinated axons in optic nerves of adult mice deficient in
      the myelin-associated glycoprotein (MAG).
AB  - We have recently demonstrated that the formation of myelin sheaths in the optic
      nerve of young postnatal mice deficient in the myelin-associated glycoprotein
      (MAG) is retarded when compared to age-matched wild-type mice. In the present
      study, we analyzed whether impaired myelination of retinal ganglion cell axons is
      detectable in adult MAG mutants. In optic nerves of 2- and 9-month-old MAG
      deficient mice, we observed a significantly increased number of unmyelinated
      axons compared to age-matched wild-type mice. At both ages, unmyelinated axons in
      optic nerves of MAG mutants were of small caliber. The number of unmyelinated
      axons decreased significantly in 9-month-old MAG mutants when compared to 2-month
      old MAG mutants, indicative of a slow and long-lasting myelination of axons in
      the mutant. Our observations support the view that MAG is involved in the
      initiation of myelination in the CNS.

PMID- 9262181
TI  - G-proteins are involved in riluzole inhibition of high voltage-activated calcium
      channels in rat dorsal root ganglion neurons.
AB  - Effects of riluzole on high voltage-activated (HVA) calcium channels of rat
      dorsal root ganglion neurons were studied using the whole-cell patch-clamp
      technique. Riluzole at 30 microM inhibited the HVA currents. The onset and offset
      of riluzole inhibitory effect were slow usually taking more than 3 min. Riluzole
      inhibition of the HVA currents was abolished and partially reduced by addition of
      500 microM GDP-beta-S and 1 mM N-ethylmaleimide, respectively, to the pipette
      solution. Pre-treatment with pertussis toxin or application of depolarizing pre
      pulses did not affect riluzole's inhibitory effect on the HVA currents. Riluzole
      inhibition of the HVA currents was also blocked by internal application of 50
      microg/ml protein kinase A inhibitory peptide. It was concluded that pertussis
      toxin-insensitive G-proteins and protein kinase A may be involved in riluzole
      inhibition of the HVA currents.

PMID- 9262182
TI  - Delayed neuronal death prevented by inhibition of increased hydroxyl radical
      formation in a transient cerebral ischemia.
AB  - The salicylate-trapping method was used to detect hydroxyl radicals by
      measurement of stable adduct dihydroxybenzoic acid (DHBA). Ten minutes of
      forebrain ischemia followed by reperfusion induced the increase in DHBA in rat
      hippocampal perfusates. Postischemic treatment with a free radical scavenger, 3
      methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), significantly reduced the increase
      in DHBA and suppressed delayed neuronal death in the hippocampal CA1 region.

PMID- 9262183
TI  - Glutamate as a primary afferent neurotransmitter in the medial vestibular nucleus
      as detected by in vivo microdialysis.
AB  - An in vivo microdialysis study using alpha-chloralose-anesthetized cats was
      performed to elucidate whether glutamate is actually released from the vestibular
      nerve terminals in the medial vestibular nucleus (MVN) with electrical
      stimulation of the vestibular nerve. When repetitive stimuli composed of
      rectangular pulses (200 micros in duration, 0.5 mA, and 0.1-50 Hz) were applied
      to the vestibular nerve for 10 min, a significant frequency-dependent increase in
      the release of glutamate was observed in the MVN. However, the levels of other
      amino acids such as aspartate, glycine and GABA remained unaltered with the
      stimuli. These findings indicate that glutamate is the primary afferent
      neurotransmitter from the vestibular nerve to the MVN neurons.

PMID- 9262184
TI  - Presence and characterization of nociceptin (orphanin FQ) receptor binding in
      adult rat and human fetal hypothalamus.
AB  - High affinity and saturable nociceptin (orphanin FQ) receptors were detected and
      characterized in adult rat and human fetal hypothalamic membranes, utilizing
      [125I]Tyr12-nociceptin as ligand. Nociceptin bound with picomolar affinity,
      dynorphin A with nanomolar affinity, naloxone and dynorphan A(1-8) with
      micromolar while des-Tyr1-dynorphin (dynorphin A(2-17)), several other opioids,
      morphine and benzomorphans failed to compete for binding at 1-10 microM. Gpp(NH)p
      together with sodium ion markedly decreased binding, consistent with involvement
      of a G protein-linked receptor.

PMID- 9262185
TI  - Astroglial expression of hepatocyte growth factor and hepatocyte growth factor
      activator in human brain tissues.
AB  - Hepatocyte growth factor (HGF) is a potent mitogen for mature hepatocytes, and
      also has multifunctional effects on some other cells in various organs. A HGF
      activating protease, HGF activator (HGFA) has recently been identified as a key
      enzyme that regulates the activity of HGF in vivo. HGFA appears to be associated
      with the cell surface. We examined HGFA immunolabelling in the brains of
      neurologically normal and Alzheimer disease (AD) cases. Furthermore, we
      identified the expression of the mRNA for HGF and HGFA by in situ hybridization
      histochemistry. The HGFA antibody stained only astrocytes in the white matter in
      all the brain tissues. Expression of the mRNAs of HGF and HGFA was also seen in
      white matter astrocytes. These results suggest that, in human brain, secreted pro
      HGF from astrocytes might be activated by HGFA on/or near the astrocytic cell
      surface.

PMID- 9262186
TI  - N-acetylcysteine protects against age-related increase in oxidized proteins in
      mouse synaptic mitochondria.
AB  - Since it has been proposed that oxidized protein accumulation plays a critical
      role in brain aging, we have investigated the effect of a thiolic antioxidant on
      protein carbonyl content in synaptic mitochondria from female OF-1 mice. At 48
      weeks of age, a control group was fed standard food pellets and another group
      received pellets containing 0.3% (w/w) of N-acetylcysteine. A 24-week treatment
      resulted in a significant decrease in protein carbonyl content in synaptic
      mitochondria of the N-acetylcysteine-treated animals as compared to age-matched
      controls.

PMID- 9262187
TI  - Expression of cyclooxygenase-2 mRNA in rat retrosplenial cortex following
      administration of phencyclidine.
AB  - The effect of NMDA receptor antagonist phencyclidine (PCP) on expression of
      cyclooxygenase (COX)-2 mRNA in the rat brain was studied. Administration of PCP
      (12.5, 25 or 50 mg/kg, i.p., 6 h) caused marked induction of COX-2 mRNA and heat
      shock gene hsp-70 mRNA, a marker of neuronal injury, in the retrosplenial cortex,
      in a dose-dependent manner. These results suggest that COX-2 may play a role in
      the neurotoxicity of NMDA receptor antagonists.

PMID- 9262188
TI  - The subnucleus reticularis dorsalis is involved in antinociception produced by a
      low dose of naloxone during carrageenan-induced inflammation.
AB  - The present study was designed to investigate a role of the subnucleus
      reticularis dorsalis (SRD) in the analgesia produced by a low dose of naloxone
      during carrageenan-induced inflammation. Male Sprague-Dawley rats were divided
      into the following two groups: (1) rats with bilateral lesions of the SRD (n =
      13) and 2) sham-operated rats (n = 24). In each group, effects of a low dose of
      naloxone (5 microg/kg, i.p.) on thermal nociception were examined 4 h, 7 and 28
      days after the induction of unilateral inflammation. Carrageenan (6 mg in 0.15 ml
      saline) was injected subcutaneously into the plantar surface of the left hindpaw.
      The analgesic effect was assessed by prolongation of the paw withdrawal latency
      (PWL) to heating. Prior to carrageenan injection, a low dose of naloxone did not
      prolong PWLs in either group. Four hours after carrageenan, a low dose of
      naloxone produced a prolongation of PWLs in both sham-operated and SRD-lesioned
      rats. Seven days after carrageenan, naloxone failed to produce analgesia in the
      SRD-lesioned rats but did produce analgesia in the sham-operated rats. At 28
      days, a low dose of naloxone induced hyperalgesia in the inflamed paw of both
      groups, whereas naloxone was ineffective in the contralateral non-inflamed paw.
      These results suggest that the SRD plays a role in naloxone-induced analgesia
      during the subacute phase of inflammation (e.g. 7 days after induction of
      inflammation).

PMID- 9262189
TI  - The decrease of serotonin release induced by a tryptophan-free amino acid diet
      does not affect spatial and passive avoidance learning.
AB  - We assessed whether consumption of a diet lacking in tryptophan (TRP) resulted in
      alteration in learning and memory performance and hippocampal 5-HT release in
      rats. Two hours after the acute administration of TRP-free (T) and balanced (B)
      diet rats were trained in a one-trial passive avoidance task. The two groups of
      rats showed no significant difference in retention latencies. Two other groups of
      rats, fed with the above diets during the acquisition of a radial-arm maze task,
      showed no difference in baseline performance. The acute ingestion of the T diet
      produced a significant and long lasting decrease of hippocampal and cortical 5-HT
      release in rats when compared to the B diet, while the 12th day of the T diet, 5
      HT was not detectable in the dialysate. These data indicate that the diminished
      brain release of 5-HT induced by a T diet is not sufficient to impair cognitive
      processes.

PMID- 9262190
TI  - Differential labelling of primary olfactory system subcomponents by SBA (lectin)
      and NADPH-d histochemistry in the frog Pipa.
AB  - SBA and NADPH-d histochemistries allow identification of functionally distinct
      components of the amphibian primary olfactory system. In Pipa, a secondarily
      aquatic frog, combination of both methodologies, using alternate sets of
      histological sections, reveals that, apart from Jacobson's organ, this species
      has a "water-nose" and an "air-nose". The epithelia occupy separate chambers of
      the olfactory organ and give rise to olfactory nerve fiber bundles that are
      identified by the dual staining procedure.

PMID- 9262191
TI  - Selective dopamine depletion within the medial prefrontal cortex induces
      anxiogenic-like effects in rats placed on the elevated plus maze.
AB  - The objective of this study was to investigate if selective dopamine depletion
      within the medial prefrontal cortex modifies the anxiety state in rats. Anxiety
      was evaluated by using the elevated plus maze test, an anxiety model. Dopamine
      depletion in the medial prefrontal cortex (79% vs. controls) induced a
      significantly lower preference to stay on open arms together with a reliably
      lower frequency of open arm entries, as well as a significant increase of percent
      time spent on closed arms. Although locomotion was also significantly reduced,
      protected head-dipping and protected stretched attend, novel "ethologically
      derived" indices of anxiety, were reliably enhanced. Taken together, the results
      are indicative of enhanced anxiety level despite hypomotility. The findings
      confirm that prefrontocortical dopamine activation is necessary for coping with
      an anxiogenic challenge, allowing the animal to display adaptive exploratory
      responses in a fear-inducing environment.

PMID- 9262192
TI  - Human amylin mimics amyloid beta protein-induced reactive gliosis and inhibition
      of cellular redox activity in cultured astrocytes.
AB  - We have previously found that Alzheimer's disease amyloid beta protein (A beta)
      induces reactive gliosis and inhibits cellular redox activity of astrocytes. In
      the present study, human amylin, an amyloidogenic peptide with primary sequence
      dissimilar to A beta, mimicked the effects of A beta in cultured astrocytes.
      However, the non-amyloidogenic rat amylin showed no effect. These results suggest
      that amyloidogenic property is important for A beta to induce morphological and
      functional changes of astrocytes.

PMID- 9262193
TI  - Excitatory connections between neurons of the central cervical nucleus and
      vestibular neurons in the cat.
AB  - The central cervical nucleus (CCN) of the cat receives input from upper cervical
      muscle afferents, particularly primary spindle afferents. Its axons cross in the
      spinal cord, and while in the contralateral restiform body give off collaterals
      to the vestibular nuclei. In order to study the connections between CCN axons and
      vestibular neurons, we stimulated the area of the CCN in decerebrate cats while
      recording intra- or extracellularly from neurons in the contralateral vestibular
      nuclei. CCN stimulation evoked excitatory postsynaptic potentials (EPSPs) or
      extracellularly recorded firing in the lateral, medial and descending vestibular
      nuclei. The latency of EPSPs (mean 1.6 ms) was on average 0.4 ms longer than the
      latency of antidromic spikes evoked in the CCN by stimulation of the
      contralateral vestibular nuclei (mean 1.2 ms), demonstrating that the excitation
      was typically monosynaptic. The results provide further evidence that the CCN is
      an important excitatory relay between upper cervical muscle afferents and neurons
      in the contralateral vestibular nuclei.

PMID- 9262194
TI  - Patterns of connectivity of spinal interneurons with single muscle afferents.
AB  - A technique was developed to measure, in the anesthetized and paralyzed cat under
      artificial ventilation, changes of excitability to intraspinal stimulation
      simultaneously in two different afferent fibers or in two collaterals of the same
      afferent fiber. Intraspinal stimulation reduced the threshold of single muscle
      afferent fibers ending in the intermediate nucleus. This effect was seen with
      strengths below those required to activate the afferent fiber tested (1.5-12
      microA), occurred at a short latency (1.5-2.0 ms), reached a maximum between 15
      and 30 ms, and lasted up to 100 ms. The effects produced by graded stimulation
      applied at the shortest conditioning-testing stimulus time intervals increased by
      fixed steps, suggesting recruitment of discrete elements, most likely of last
      order interneurons mediating primary afferent depolarization (PAD). The short
      latency increases in excitability produced by the weakest effective intraspinal
      stimuli were usually detected only in the collateral closest to the stimulating
      micropipette, indicating that the stimulated interneurons mediating PAD have
      spatially restricted actions. The short-latency PAD produced by intraspinal
      stimuli, as well as the PAD produced by stimulation of the posterior biceps and
      semitendinosus (PBSt) nerve or by stimulation of the bulbar reticular formation
      (RF), was depressed 19-30 min after the i.v. injection of 0.5 mg/kg of
      picrotoxin, suggesting that all these effects were mediated by GABAergic
      mechanisms. The PAD elicited by stimulation of muscle and/or cutaneous nerves was
      depressed following the i.v. injection of (-)-baclofen, whereas the PAD elicited
      in the same collateral by stimulation of the RF was baclofen-resistant. The short
      latency PAD produced by intraspinal stimulation was not always depressed by i.v.
      injections of (-)-baclofen. Baclofen-sensitive and baclofen-resistant
      monosynaptic PADs could be produced in different collaterals of the same afferent
      fiber. The results suggest that the intraspinal terminals of single muscle
      afferents receive synapses from more than one PAD-mediating GABAergic interneuron
      and that a single last-order interneuron has synaptic connections with a
      restricted number of intraspinal terminals and/or collaterals of the same
      afferent fiber. In addition, they support the existence of separate subsets of
      last-order baclofen-sensitive and baclofen-resistant interneurons that respond
      predominantly to segmental and to descending inputs. It is suggested that the
      restricted nature of the PAD plays an important role in the central control of
      the synaptic effectiveness of group I muscle afferents.

PMID- 9262195
TI  - Subthreshold receptive fields and baseline excitability of "silent" S1 callosal
      neurons in awake rabbits: contributions of AMPA/kainate and NMDA receptors.
AB  - The contribution of NMDA and non-NMDA receptors to excitatory subthreshold
      receptive fields was examined in callosal efferent neurons (CC neurons) in
      primary somatosensory cortex of the fully awake rabbit. Only neurons showing no
      traditional (suprathreshold) receptive fields were examined. Subthreshold
      responses were examined by monitoring the thresholds of efferent neurons to
      juxtasomal current pulses (JSCPs) delivered through the recording microelectrode.
      Changes in threshold following a peripheral conditioning stimulus signify a
      subthreshold response. Using this method, excitatory postsynaptic potentials and
      inhibitory postsynaptic potentials are manifested as decreases and increases in
      JSCP threshold, respectively. NMDA and non-NMDA agonists and antagonists were
      administered iontophoretically via a multibarrel micropipette assembly attached
      to the recording/stimulating microelectrode. Receptor-selective doses of both
      AMPA/kainate and NMDA antagonists decreased the excitability of CC neurons in the
      absence of any peripheral stimulation. Threshold to JSCPs rose by a mean of 20%
      for both classes of antagonist. Despite the similar effects of NMDA and non-NMDA
      antagonists on baseline excitability, these antagonists had dramatically
      different effects on the subthreshold excitatory response to activation of the
      receptive field. Whereas receptor-selective doses of AMPA/kainate antagonists
      either eliminated or severely attenuated the subthreshold excitatory responses to
      peripheral stimulation, NMDA antagonists had little or no effect on the
      subthreshold evoked response.

PMID- 9262196
TI  - Cellular and developmental patterns of expression of Ret and glial cell line
      derived neurotrophic factor receptor alpha mRNAs.
AB  - Glial cell line-derived neurotrophic factor (GDNF) has recently been shown to
      signal by binding to GDNF receptor-alpha (GDNFR-alpha), after which the GDNF
      GDNFR-alpha associates with and activates the tyrosine kinase receptor Ret. We
      have localized Ret messenger RNA (mRNA) in the developing and adult rodent and
      compared with to the expression of GDNF and GDNFR-alpha mRNA. Ret mRNA is
      strongly expressed in dopamine neurons and alpha-motor neurons as well as in
      thalamus, ruber and occluomotor nuclei, the habenular complex, septum,
      cerebellum, and brain stem nuclei. Ret mRNA was also found in several sensory
      systems, in ganglia, and in nonneuronal tissues such as teeth and vibrissae. Very
      strong Ret mRNA signals are present in kidney and the gastrointestinal tract,
      where Ret and GDNF mRNA expression patterns are precisely complementary. The
      presence of Ret protein was confirmed in adult dopamine neurons using
      immunohistochemistry. GDNFR-alpha mRNA was strongly expressed in the developing
      and adult dopamine neurons. It was also found in neurons in deep layers of cortex
      cerebri, in hippocampus, septum, the dentate gyrus, tectum, and the developing
      spinal cord. In the kidney and the gastrointestinal tract, GDNFR-alpha mRNA and
      Ret mRNA distribution overlapped. Dorsal root ganglia, cranial ganglia, and
      developing peripheral nerves were also positive. GDNFR-alpha was additionally
      found in sensory areas and in developing teeth. Sensory areas included inner ear,
      eye, olfactory epithelium, and the vomeronasal organ, as well as developing
      tongue papillae. The temporospatial pattern of expression of GDNFR-alpha mRNA did
      not always match that of Ret mRNA. For instance, GDNFR-alpha mRNA was also found
      in the developing ventral striatum, including the olfactory tubercle, and in
      hippocampus. These areas seemed devoid of Ret mRNA, suggesting that GDNFR-alpha
      might also have functions unrelated to Ret.

PMID- 9262197
TI  - Ischemia changes the coexpression of somatostatin and neuropeptide Y in
      hippocampal interneurons.
AB  - Transient cerebral ischemia causes extensive cell death in hippocampal CA1
      pyramidal cells and selective loss of interneurons in the dentate hilus. Many
      hippocampal interneurons can be classified by their contents of somatostatin (SS)
      and/or neuropeptide Y (NPY). Following ischemia in the rat, most of the NPY
      immunoreactivity is permanently lost in hippocampus. Furthermore, SS interneurons
      in the dentate hilus die, whereas CA1 interneurons survive and their expression
      of SS mRNA and peptide returns to preischemic levels within 16 days after
      ischemia. We have addressed the following questions: (1) Does the loss of NPY
      involve a specific downregulation in surviving CA1 interneurons that pre
      ischemically expressed both SS and NPY? (2) Can the subpopulation of dying
      interneurons in hilus be identified from their preischemic coexpression of SS and
      NPY? We investigated the coexpression of SS mRNA and NPY peptide using combined
      in situ hybridization and immunocytochemistry. Cells containing one or both
      markers were counted in control sections and sections taken 2-16 days after
      ischemia from the hippocampal formation. In CA1, a decrease in the number of
      neurons containing NPY alone as well as a decrease in the number of neurons
      coexpressing NPY and SS was observed, whereas the number of neurons containing SS
      alone increased 16 days after ischemia. We conclude that neurons coexpressing SS
      and NPY before ischemia added to the number of neurons containing SS alone after
      ischemia, because NPY expression was selectively down regulated in the
      coexpressing population. In hilus, we demonstrated both survival and ischemic
      cell death of neurons expressing either SS, NPY or both, indicating that hilar
      interneurons dying from ischemia cannot unequivocally be identified from their
      preischemic colocalization of SS and NPY.

PMID- 9262198
TI  - Thalamic and temporal cortex input to medial prefrontal cortex in rhesus monkeys.
AB  - To determine the source of thalamic input to the medial aspect of the prefrontal
      cortex, we injected retrograde tracers (wheat germ agglutinin conjugated to
      horseradish peroxidase, nuclear yellow, and/or bisbenzimide) into seven medial
      prefrontal sites and anterograde tracers (tritiated amino acids) into six
      thalamic sites, in a total of nine rhesus monkeys. The results indicated that
      ventral precallosal and subcallosal areas 14 and 25, and the ventral, subcallosal
      part of area 32, all receive projections from the mediodorsal portion of the
      magnocellular division of the medial dorsal nucleus (MDmc). The dorsal,
      precallosal part of area 32 receives projections mainly from the dorsal portion
      of the parvocellular division of the medial dorsal nucleus (MDpc), which also
      provides some input to area 14. Polar area 10 receives input from both MDpc and
      the densocellular division of the medial dorsal nucleus (MDdc), as does
      supracallosal area 24. Area 24 receives additional input from the anterior medial
      nucleus and midline nuclei. All medial prefrontal cortical areas were also found
      to receive projections from a number of cortical regions within the temporal
      lobe, such as the temporal pole, superior temporal gyrus, and parahippocampal
      gyrus. Areas 24, 25, and 32 receive, in addition, input from the entorhinal
      cortex. Combining these results with prior anatomical and behavioral data, we
      conclude that medial temporal areas that are important for object recognition
      memory send information directly both to dorsal medial prefrontal areas 24 and 32
      and to ventral medial prefrontal areas 14 and 25. Only the latter two areas have
      additional access to this information via projections from the mediodorsal part
      of MDmc.

PMID- 9262199
TI  - Lesions of the entorhinal cortex disrupt behavioral and neuronal responses to
      context change during extinction of discriminative avoidance behavior.
AB  - Rabbits given either electrolytic lesions of the entorhinal cortex or sham
      lesions were trained to prevent a foot-shock by stepping in an activity wheel
      after one tone, a positive conditioned stimulus (CS+), and to ignore a different
      tone, a negative conditioned stimulus (CS-). Neuronal activity was recorded
      simultaneously in the basolateral nucleus of the amygdala, the CA1 cell field of
      hippocampus, anterior cingulate cortical area 24b and posterior cingulate
      cortical area 29c/d. The activity of neurons in the entorhinal cortex was
      recorded in the controls. Acquisition of conditioned avoidance responses (CRs)
      was not affected by lesions of the entorhinal cortex. Discriminative neuronal
      activity (greater neuronal responses to the CS+ than to the CS-) during CR
      acquisition was significantly enhanced in hippocampal area CA1 and attenuated in
      the basolateral amygdala in rabbits with lesions. Following acquisition to a
      criterion, two counterbalanced extinction tests were administered, one in the
      original context and the other in the presence of novel contextual stimuli. CR
      frequency was significantly reduced in controls but not in rabbits with lesions,
      during extinction with novel contextual stimuli, relative to performance in the
      original context. The rabbits with lesions also showed fewer inter-trial
      responses than controls during extinction in the original context but intertrial
      response frequency in rabbits with lesions did not differ from the frequency in
      controls during extinction in the novel context. Neurons in the basolateral
      amygdala in controls showed discriminative activity during extinction in the
      original context but not in the novel context. Amygdalar neurons in the rabbits
      with lesions did not show discriminative activity during extinction in either
      context. Posterior cingulate cortical neurons in control rabbits did not show
      discriminative activity during extinction in the original context but these
      neurons exhibited robust discriminative activity in the novel context. Posterior
      cingulate cortical neurons in rabbits with lesions showed discriminative activity
      in both extinction sessions. The results indicated that the entorhinal cortex
      does not play a significant role in the acquisition of discriminative avoidance
      behavior, under the employed conditions of training. However, the interactions of
      neurons in the entorhinal cortex, amygdala and cingulate cortex are essential for
      contextual modulation of CRs during extinction.

PMID- 9262201
TI  - Differential effect of task conditions on errors of direction and extent of
      reaching movements.
AB  - Invariant patterns in the distribution of the endpoints of reaching movements
      have been used to suggest that two important movement parameters of reaching
      movements, direction and extent, are planned by two independent processing
      channels. This study examined this hypothesis by testing the effect of task
      conditions on variable errors of direction and extent of reaching movements.
      Subjects made reaching movements to 25 target locations in a horizontal
      workspace, in two main task conditions. In task 1, subjects looked directly at
      the target location on the horizontal workspace before closing their eyes and
      pointing to it. In task 2, arm movements were made to the same target locations
      in the same horizontal workspace, but target location was displayed on a vertical
      screen in front of the subjects. For both tasks, variable errors of movement
      extent (on-axis error) were greater than for movement direction (off-axis error).
      As a result, the spatial distributions of endpoints about a given target usually
      formed an ellipse, with the principal axis oriented in the mean movement
      direction. Also, both on- and off-axis errors increased with movement amplitude.
      However, the magnitude of errors, especially on-axis errors, scaled differently
      with movement amplitude in the two task conditions. This suggests that variable
      errors of direction and extent can be modified independently by changing the
      nature of the sensorimotor transformations required to plan the movements. This
      finding is further evidence that the direction and extent of reaching movements
      appear to be controlled independently by the motor system.

PMID- 9262200
TI  - Treadmill running induces striatal Fos expression via NMDA glutamate and dopamine
      receptors.
AB  - Several non-physiological stimuli (i.e. pharmacological or electrical stimuli)
      have been shown to induce Fos expression in striatal neurons. In this work,
      striatal Fos (i.e. Fos-like) expression was studied after physiological
      stimulation, i.e. motor activity (treadmill running at 36 m/min for 20 min). In
      rats killed 2 h after the treadmill session, Fos expression was observed in the
      medial region of the rostral and central striatum, and in the dorsal region of
      the caudal striatum. Fos expression was prevented by pretreatment with the non
      competitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist MK-801 (0.1
      mg/kg) or the D1 dopamine receptor antagonist SCH-23390 (0.1 mg/kg), but not by
      pretreatment with the D2 receptor antagonist eticlopride (0.5 mg/kg). Thirty-six
      hours after 6-hydroxydopamine lesion, a considerable reduction in treadmill
      induced Fos expression was observed in both sides; however, Fos expression in the
      lesioned striatum was higher than in the contralateral intact striatum. Several
      weeks after unilateral 6-hydroxydopamine lesion of the nigrostriatal system,
      treadmill-induced Fos expression was significantly, but not totally, reduced in
      the lesioned striatum. Corticostriatal deafferentation also led to considerable
      reduction in treadmill-induced Fos expression. The present results indicate that
      exercise induces striatal Fos expression and that, under physiological
      stimulation, concurrent activation of D1 and NMDA receptors is necessary for such
      expression to occur. Reduction of Fos expression is practically absolute after
      acute blockage of these receptors, but not after lesions, possibly due partially
      to compensatory changes.

PMID- 9262202
TI  - Influence of pre-target cortical potentials on saccadic reaction times.
AB  - Saccades elicited by suddenly appearing targets show a broad distribution of
      reaction times. This may depend on variations in the subject's state of
      preparation before target onset. To test this hypothesis, we recorded scalp event
      related potentials from eight human subjects to investigate whether differences
      in saccadic reaction times (SRTs) are related to differences in cortical slow
      potentials prior to target onset. Compared with trials with medium SRTs (180-230
      ms), trials with fast SRTs (130-180 ms) were found to be preceded by a more
      negative slow potential and trials with slow SRTs (230-280 ms) were found to be
      preceded by a more positive slow potential. These results support the hypothesis
      that cortical activation prior to target appearance influences SRTs.

PMID- 9262204
TI  - Neural firing in ventrolateral thalamic nucleus during conditioned vocal behavior
      in cats.
AB  - The ventrolateral (VL) thalamus in mammals is a site well-situated to show
      vocalization-related neural activity if there is general or classical motor
      system involvement in vocal production. It receives input from both the basal
      ganglia and cerebellum, and forms reciprocal connections with motor cortical
      areas. The current study examined the activity in cat VL thalamus neurons during
      instrumentally conditioned vocalization. Units in our sample showed irregular
      spontaneous firing which could be modulated by slowly occurring fluctuations in
      intensity of vocalization task performance. Two main types of behavioral events
      were associated with changes in neural firing rate. The first of these was the
      ingestion of food reward. More than half of all recordings showed phasic bursting
      patterns during licking; a similar number had increases in firing preparatory to
      this phasic activity. The second behavioral event modulating unit responses was
      vocalization. Approximately 60% of recordings showed activity changes time-locked
      to vocalization. These responses were almost always excitatory, and often
      involved changes in firing that preceded vocalization onset. No spatial
      organization of differences in firing pattern between neurons could be
      distinguished. Our results suggest that VL thalamus may well be involved in
      mediating vocal behavior, although its functional role remains an object of
      speculation. Results are compared with previous studies of vocalization-related
      activity and of VL thalamus activity.

PMID- 9262203
TI  - Modulation of the spinal network for locomotion by substance P in the neonatal
      rat.
AB  - The tachykinin substance P (SP) is present in the ventral and medial area of the
      lumbar spinal cord. Its localisation suggests that it could modulate the spinal
      network for locomotion. We have investigated its effects on motor outputs by
      applying SP, in vitro, to the lumbosacral segments of an isolated spinal cord of
      new-born rats. SP was applied to the lumbosacral spinal cord either on a
      quiescent preparation or during episodes of fictive locomotion induced by N
      methyl-D,L-aspartate. When applied on quiescent preparations, SP induced a slow
      rhythmic activity (period >30 s). During fictive locomotion, SP increased both
      the locomotor frequency and the duration of the bursts of cyclic activity.
      Furthermore, SP stabilised the locomotor rhythm. These results demonstrate that
      SP is able to modulate both the "clock" and the pattern generator for locomotion.

PMID- 9262205
TI  - Effects of a tilted visual background on human sensory-motor coordination.
AB  - The present study investigated the effects of a tilted visual background on
      perceived hand orientation, and on the execution of aimed arm movements. Subjects
      were seated in a room tilted about their mid-sagittal axis to the left or right.
      They were asked to indicate the gravitational vertical or the body midline by
      rotating their supported or free, unseen hand about the longitudinal forearm
      axis. They were further asked to draw vertical lines with their unseen arm, and
      to point with the hand at visual targets. Our results indicate that if the hand
      is stationary, tilted environments induce an illusory hand and body tilt in the
      opposite direction; the effects on the hand is substantially smaller than that on
      the body. We found no evidence for illusory hand tilt with line drawing, and
      pointing movements were not noticeably modified by background tilt. We concluded
      that the latter two tasks provide dynamic cues about hand orientation, which
      remain veridical in tilted environments, and can be utilized for fast corrections
      of motor commands.

PMID- 9262207
TI  - Behavioral effects of GM1 ganglioside treatment and intrahippocampal septal
      grafts in rats with fimbria-fornix lesions.
AB  - The monosialoganglioside GM1 is a compound with neurotrophic properties found to
      foster functional recovery in various paradigms of brain damage. The present
      experiment examined whether systemic treatment with GM1 may facilitate behavioral
      recovery in rats with fimbria-fornix lesions and intrahippocampal grafts rich in
      cholinergic neurons. Among 68 Long-Evans female rats, 46 sustained a bilateral
      electrolytic lesion of the fimbria and the dorsal fornix and 22 were sham
      operated. Fourteen days later, half the lesioned rats were subjected to
      intrahippocampal grafts of a fetal septal cell suspension. Starting a few hours
      after lesion surgery and over a 2-month period, half the rats of each surgical
      treatment group received a daily injection of GM1 (30 mg/kg i.p.), the other half
      being injected with saline as a control. All rats were subsequently tested for
      locomotor activity and radial maze learning. The lesions induced locomotor
      hyperactivity and impaired learning performances in both an uninterrupted and an
      interrupted radial maze testing procedure. In all rats with surviving grafts, the
      grafts had provided the hippocampus with a new and dense organotypic
      acetylcholinesterase-positive innervation pattern which did not differ between
      saline- and GM1-treated subjects. The scores/performances of the rats that had
      received only the grafts or only the GM1 treatment did not differ significantly
      from those of their respective lesion-only counterparts. However, in the radial
      arm maze task, the grafted rats given GM1 showed improved learning performances
      as compared with their saline-treated counterparts: they used more efficient
      visit patterns under the uninterrupted testing conditions and made fewer errors
      under the interrupted ones. The results suggest that GM1 treatment or
      intrahippocampal grafts used separately do not attenuate the lesion-induced
      behavioral deficits measured in this experiment. However, when GM1 treatment and
      grafts are used conjointly, both may interact in a manner allowing part of these
      deficits to be attenuated.

PMID- 9262206
TI  - The nucleus retroambigualis controls laryngeal muscle activity during
      vocalization in the cat.
AB  - The purpose of this study was to determine (1) whether the nucleus
      retroambigualis (NRA) plays an essential role in periaqueductal gray (PAG)
      induced vocalization and (2) which NRA neurons are involved in the projection
      from the PAG to laryngeal motoneurons. Bilateral injections of the neurotoxin
      kainic acid into the NRA in decerebrate cats abolished PAG-induced vocalization;
      PAG stimulation after the injections no longer modulated vocal fold adductor or
      tensor activity, and only tonically, but no longer phasically, activated the
      abdominal muscles. In contrast, PAG-induced inspiratory excitation remained even
      after the injections. These results suggest that the NRA is essential for the
      vocal activation of the laryngeal adductor and abdominal muscles, and that an
      additional pathway from the PAG to respiratory motoneurons other than through the
      NRA is important for mediating PAG-induced inspiratory activation. Secondly,
      axonal projections of NRA neurons to the contralateral nucleus ambiguus (NA) were
      studied electrophysiologically. Five expiratory neurons, which had decrementing
      (n=4) or constant (n=1) firing patterns, were identified as both having axonal
      projections to the NA and receiving inputs from the PAG. Furthermore, following
      NA stimulation many constant-latency action potentials of silent cells were
      recorded in the vicinity of the NRA, where many silent cells were also
      orthodromically activated by PAG stimulation. No NRA augmenting expiratory
      neurons could be antidromically activated from the NA. It is suggested that the
      NRA and adjacent reticular formation integrate inputs from the PAG and send
      outputs to laryngeal motoneurons for vocalization.

PMID- 9262208
TI  - The influence of stationary and moving textured backgrounds on smooth-pursuit
      initiation and steady state pursuit in humans.
AB  - We investigated the effects of stationary and moving textured backgrounds on the
      initiation and steady state of ocular pursuit using horizontally moving targets.
      We found that the initial eye acceleration was slightly reduced when a stationary
      textured background was employed, as compared to experiments with a homogeneous
      background. When a moving textured background was introduced, the initial eye
      acceleration was significantly larger when the target and the background moved in
      opposite directions than when the target and the background moved in the same
      direction. The use of stationary and moving textured backgrounds resulted in
      comparable effects on the initial eye acceleration when they were presented
      either as a large field or as a narrow, horizontal small field, only covering the
      trajectory of the target. Moreover, small-field stationary backgrounds slightly
      reduced the eye velocity during steady state pursuit. A small-field background
      moving in the opposite direction to the target distinctly reduced eye velocity,
      while a target and a background moving in the same direction sometimes even
      improved pursuit performance, when compared with a homogeneous background. The
      influences of small-field textured backgrounds on steady state pursuit were
      comparable with those of large-field backgrounds in both stationary and moving
      conditions.

PMID- 9262209
TI  - Shortening of simple reaction time by peripheral electrical and submotor
      threshold magnetic cortical stimulation.
AB  - Subthreshold transcranial magnetic stimulation (TMS) over the motor cortex can
      shorten the simple reaction time in contralateral arm muscles if the cortical
      shock is given at about the same time as the reaction stimulus. The present
      experiments were designed to investigate whether this phenomenon is due to a
      specific facilitatory effect on cortical circuitry. The simple visual reaction
      time was shortened by 20-50 ms when subthreshold TMS was given over the
      contralateral motor cortex. Reaction time was reduced to the same level whether
      the magnetic stimulus was given over the bilateral motor cortices or over other
      points on the scalp (Cz, Pz). Indeed, similar effects could be seen with
      conventional electrical stimulation over the neck, or even when the coil was
      discharged (giving a click sound) near the head. We conclude that much of the
      effect of TMS on simple reaction time is due to intersensory facilitation,
      although part of it may be ascribed to a specific effect on the excitability of
      motor cortex.

PMID- 9262210
TI  - Changes in the permeability of the blood-brain barrier following sodium dodecyl
      sulphate administration in the rat.
AB  - The blood-brain barrier (BBB) arises from epithelial-like tight junctions that
      virtually cement adjoining capillary endothelium together in the brain
      microvasculature. Several experimental manipulations have been shown able to
      increase the permeability of brain capillaries, by altering endothelial cell
      membrane integrity or activating specific biochemical pathways involved in
      regulation of BBB functionality. Because of its amphiphilic nature, sodium
      dodecyl sulphate (an anionic surfactant widely used as solubilizer or stabilizer
      in several pharmaceutical preparations; SDS) may enter into interactions with the
      major membrane components, which are lipids and proteins. The aim of the present
      study was to determine the effect of an intracarotid infusion of SDS (25, 50 and
      100 microg/kg; infusion rate: 3 ml/min for 30 s) on the functionality of the BBB
      in the rat. An extensive, dose-dependent Evans blue extravasation was observed,
      in the ipsilateral brain hemisphere, 15 min following SDS infusion. These results
      were confirmed by the significant increase in [14C]alpha-aminoisobutyric acid
      ([14C]AIB) transport (evaluated by calculating a unidirectional transfer
      constant, Ki, for the tracer from blood to brain) measured in several ipsilateral
      brain regions 2 min after SDS infusion; this SDS-elicited BBB opening to [14C]AIB
      proved to be reversible. Since the BBB is created by the plasma membrane and
      tight junctions of the endothelial cells, the change in BBB permeability caused
      by SDS might be explained as a nonspecific surfactant-membrane interaction.
      Furthermore, SDS might affect the functional characteristics of brain vascular
      endothelial cells by an interaction with specific BBB proteins and/or biochemical
      pathways. In conclusion, one can suggest that intracarotid infusion of SDS might
      provide a useful clinical approach for the intentional introduction of different
      substances into the brain. On the other hand, these findings should call
      attention to possible dangerous consequences of using SDS as solubilizer in drug
      excipients.

PMID- 9262211
TI  - Arm and mouth coordination during the eating action in humans: a kinematic
      analysis.
AB  - The kinematic characteristics of the eating action in humans were assessed. Ten
      subjects were asked to bring to the mouth pieces of cheese of different sizes
      (0.7 cm and 2 cm). The pattern of mouth aperture with respect to the size of the
      food was similar to that found for grasping differently sized objects with the
      hand. Mouth aperture was appropriately scaled and the time of maximum aperture
      was reached earlier for the smaller than for the larger piece of cheese. The
      deceleration phase of the arm was prolonged when the small piece of cheese had to
      be brought to the mouth with respect to when the large piece of cheese had to be
      brought to the mouth. Temporal coupling between the time of maximum peak
      deceleration and the maximum mouth aperture was found in seven of the ten
      subjects. Taken together these preliminary results suggest that coordinated
      actions are subserved by the use of a common coordinating schema independently
      from the effectors involved.

PMID- 9262212
TI  - Adaptation to gradual as compared with sudden visuo-motor distortions.
AB  - If visual feedback is discordant with movement direction, the visuo-motor mapping
      is disrupted, but can be updated with practice. In this experiment subjects
      practiced discrete arm movements under conditions of visual feedback rotation.
      One group was exposed to 10 degree-step increments of visual feedback rotation up
      to a total of 90 degrees, a second group to a 90 degree visual feedback rotation
      throughout the experiment. After the first group reached the 90 degree visual
      feedback rotation, its subjects performed faster, with less spatial error, and
      showed larger aftereffects than the subjects who practiced constantly under the
      90 degree visual feedback rotation condition. Results suggest that gradually
      increasing feedback distortion allows more complete adaptation than a large,
      sudden distortion onset.

PMID- 9262214
TI  - Methylprednisolone attenuates the pulmonary hypertensive response in porcine
      meconium aspiration.
AB  - Severe neonatal aspiration of meconium is frequently complicated by fatal
      pulmonary hypertension. The protective effect of an i.v. bolus of
      methylprednisolone on meconium aspiration-induced hypertensive lung injury was
      studied in anesthetized pigs with adapted lung circulation. Eleven 10-wk-old pigs
      received 3 mL/kg 20% human meconium via the endotracheal tube. Five of them were
      pretreated with 30 mg/kg methylprednisolone 30 min before aspiration. Ventilator
      settings were adjusted to keep arterial PO2 above 8 kPa and arterial PCO2 below 5
      kPa. Meconium insufflation induced a biphasic pulmonary pressor response during
      the 6 h follow-up. Methylprednisolone tended to prevent the early (0-1 h)
      increase in pulmonary artery pressure and inhibited significantly the second
      phase (1-6 h) progressive rise in pulmonary artery pressure and pulmonary
      vascular resistance. This inhibition of resistance increase was most profound in
      the postarterial segment of the lung circulation, as determined by pulmonary
      artery occlusion. Additionally, the methylprednisolone pretreated group
      demonstrated a significant decrease in venous admixture together with improved
      oxygenation during the late phase after the insult, and further showed evidence
      of diminished lung edema formation. Although meconium aspiration-induced fall in
      blood leukocyte concentration was inhibited by methylprednisolone pretreatment,
      no histologic difference was found in pulmonary leukocyte sequestration. Our
      results thus show that in adapted porcine lungs methylprednisolone pretreatment
      improves oxygenation and attenuates the meconium aspiration-induced pulmonary
      hypertensive response by preventing the increase in the postarterial resistance.

PMID- 9262213
TI  - Indicators of delayed maturation of rat heart treated prenatally with
      dexamethasone.
AB  - We investigated the effects of prenatal dexamethasone treatment on indicators of
      cardiac maturation: heart weight/body weight ratios, myosin heavy chain (MHC)
      expression, cell proliferation, and extracellular matrix. We administered
      dexamethasone, a synthetic glucocorticoid (approximately 48 microg/d, 3-wk slow
      release pellets), to pregnant rats (n = 8) beginning at 17 d postconception.
      Control dams were unmanipulated (n = 8). After approximately 4-5 d of
      dexamethasone exposure, hearts were collected from neonatal rats (12-24 h after
      birth). The prenatal dexamethasone treatment produced smaller pups with larger
      heart/body weight ratios, accompanied by a higher proliferative index and a
      reduction in extracellular matrix in the ventricles (with lowest values in the
      septal region) compared with control pups. We also report that, although there
      were no sex differences in body mass or heart and heart/body weight ratios,
      females had a greater proportion of cells synthesizing DNA in the heart. In
      addition, ventricles of male pups treated with dexamethasone contained lower
      levels of alpha-MHC mRNA, as reflected in a sex by treatment interaction. The
      changes in each parameter are consistent with delayed maturation. Our findings
      suggest that exposure to excess glucocorticoids in utero can affect cardiac
      development in potentially detrimental ways and that assessment of cardiac
      function should be closely monitored when such circumstances arise.

PMID- 9262215
TI  - Nitric oxide contributes to surfactant-induced vasodilation in surfactant
      depleted newborn piglets.
AB  - To investigate whether nitric oxide (NO) is involved in surfactant-induced
      systemic and pulmonary vasodilatation in newborn piglets with surfactant
      deficiency, 2-6-d-old piglets were subjected to repeated saline lung lavages.
      They were then randomly assigned to one of two groups (seven in each group): the
      N(omega)-nitro-L-arginine methyl ester (L-NAME) group received 3 mg/kg L-NAME
      i.v. 45 min before endotracheal instillation of 200 mg/kg porcine surfactant; the
      saline group received saline i.v. at the same time point, and instillation of 200
      mg/kg surfactant. Mean arterial blood pressure, systemic vascular resistance,
      pulmonary arterial pressure, and pulmonary vascular resistance increased
      significantly after injection of L-NAME (all p < 0.01), whereas the cardiac index
      decreased significantly (p < 0.05). Saline injection did not change any variable.
      Significant decreases in mean arterial blood pressure (from a mean +/- SD of 66
      +/- 10 to 53 +/- 9 mm Hg, p < 0.01), pulmonary arterial pressure (from 29 +/- 6
      to 23 +/- 6 mm Hg, p < 0.01), and systemic vascular resistance (from 0.40 +/-
      0.13 to 0.33 +/- 0.12 mm Hg/mL/min/kg, p < 0.05) were observed only in the saline
      group after surfactant instillation, whereas the decrease in pulmonary vascular
      resistance was not significant after surfactant instillation (p = 0.06). In
      contrast to the saline group, these variables were not modified in the L-NAME
      group after surfactant instillation. We conclude that the vasodilatory effect of
      porcine surfactant instillation in newborn piglets with surfactant deficiency is
      associated with activation of NO synthase.

PMID- 9262217
TI  - Initiation and maintenance of continuous breathing at birth.
AB  - Changes in arterial PCO2 (PaCO2) and body temperature normally occurring at the
      moment of birth may play a role in the initiation and maintenance of continuous
      breathing. To clarify these mechanisms, five chronically instrumented fetal lambs
      were connected to an extracorporeal membrane oxygenation (ECMO) system. ECMO was
      initiated in utero at a flow rate sufficient to support the fetus totally, the
      umbilical cord was occluded, and the fetuses were delivered into a warm isotonic
      saline bath. Breathing activity was present periodically before connection to the
      ECMO system and on ECMO during fetal normocapnia and normoxia. Near delivery
      there were no breathing movements, because all ewes were in labor. After
      delivering the fetuses into the warm saline bath, breathing movements remained
      episodic, being absent during high voltage electrocortical activity, whereas
      fetal PaCO2 remained constant. However, after 36-192 min, breathing activity
      became present continuously in all animals, at a time when fetal central
      temperature decreased. Once initiated, continuous breathing could be stopped by
      reducing the PaCO2. We conclude that maintenance of fetal PaCO2 and a slow
      decrease in central temperature after cord occlusion delays the establishment of
      continuous breathing, and that the level of PaCO2 is important in the maintenance
      of breathing activity during early postnatal life.

PMID- 9262216
TI  - The effects of bronchodilators on spontaneous ventilation and oxygen consumption
      in rhesus monkeys.
AB  - The effects of breathing normal saline, salmeterol, fenoterol, ipratropium
      bromide, or formoterol, and of i.v. infusion of theophylline on oxygen
      consumption (VO2), carbon dioxide production (VCO2), minute ventilation (VE),
      heart and respiratory rates, and end-tidal carbon dioxide tension (P(ET)CO2) have
      been defined in 10 anesthetized, intubated rhesus monkeys (mean age 7.0 y, weight
      10.2 kg). VO2 increased over control by + 17.1% after salmeterol (p < 0.001),
      +33.3% after fenoterol (p < 0.001), +23.7% after formoterol (p < 0.001), +3.9%
      after theophylline (p < 0.01), but did not change after ipratropium bromide and
      normal saline. VE increased by 63.0% after fenoterol (p < 0.001), 49.8% after
      formoterol (p < 0.001), 31.7% after salmeterol (p < 0.01), and 29.7% after
      theophylline (p < 0.001), but not after ipratropium bromide or normal saline.
      Heart rate response was greatest after fenoterol, formoterol, and salmeterol,
      respectively. P(ET)CO2 dropped dramatically after theophylline (-15.7%, p <
      0.001), but not at all with any of the inhaled beta2-adrenoceptor agonists. In
      seven animals, salbutamol (albuterol) caused an increase in V(E) and VO2 of 50.1%
      and 45.9%, respectively, whereas in the presence of a beta2-adrenoceptor
      antagonist [racemic or (+/-)-propranolol (0.1 mg/kg i.v.)], inhaled salbutamol
      (2.5 mg/mL for 10 min) could not increase V(E) (+6.2%, p > 0.05) and VO2 (+1.6%,
      p > 0.05). The increase in VO2 and V(E) after administration of beta2-agonists
      may be partly the result of direct stimulation of the respiratory center and
      partly a response to increased metabolic rate. The dramatic increase in VO2 and
      V(E) after salbutamol was suppressed in the presence of propranolol, which is
      consistent with a beta-receptor-mediated mechanism.

PMID- 9262218
TI  - Surfactant dysfunction develops in BALB/c mice infected with respiratory
      syncytial virus.
AB  - Recent reports suggest an important role for pulmonary surfactant in maintaining
      the patency of narrow conducting airways. The hypothesis that surfactant
      dysfunction is an important factor in respiratory syncytial virus (RSV) infection
      was tested in a mouse model. Mice, inoculated with either a low or a high dose of
      RSV, were subjected to bronchoalveolar lavage (BAL), and the fluids were analyzed
      for percentage of inflammatory cells and concentrations of proteins and
      phospholipids. After concentration of the surfactant by centrifugation, its
      function was analyzed with a capillary surfactometer. RSV infection resulted in a
      dose-dependent disruption of surfactant function (p < 0.0001). BAL fluid
      supernatants were added to calf lung surfactant extract (CLSE) to examine whether
      surfactant inhibiting agents were present. Indeed, BAL fluid supernatants of RSV
      infected mice disrupted the normal function of calf lung surfactant extract in a
      dose dependent way (p < 0.0001), indicating the presence of inhibitors. Protein
      concentrations were increased in BAL fluids of RSV-infected mice versus control
      mice (p < 0.0001), and were inversely related to surfactant function (r = -0.44,
      p = 0.0004), suggesting an inhibitory effect of proteins. Protein concentration
      also correlated with the percentage of inflammatory cells (r = 0.51, p = 0.004).
      Phospholipid concentrations were not affected by the RSV infection. The results
      of these studies strongly suggest that a disruption of pulmonary surfactant
      function, most likely due to inhibition from inflammatory proteins, is important
      for the pathophysiology of RSV infection.

PMID- 9262219
TI  - Function of cell membranes in cerebral cortical tissue of newborn piglets after
      hypoxia and inhibition of nitric oxide synthase.
AB  - Hypoxia-induced brain cell membrane lipid peroxidation can be caused by free
      radicals that are produced during hypoxia. Recently, the production of nitric
      oxide (NO), a free radical, has been shown to be increased during cerebral
      hypoxia-ischemia. The present study tested the hypothesis that inhibition of NO
      synthase (NOS) reduced hypoxia-induced modifications of Na+,K+-ATPase activity,
      lipid peroxidation, and [3H]MK-801 binding to the N-methyl-D-aspartate (NMDA)
      receptor in cerebral cortical tissue of newborn piglets. Studies were performed
      in 26 newborn piglets. Cerebral NOS was inhibited by the i.v. administration of
      25 or 50 mg/kg N(omega)-nitro-L-arginine (NNLA) over 30 min. Control animals
      received normal saline. Six groups of piglets were thus created (normoxia, no
      NNLA; normoxia + NNLA 25 mg/kg; normoxia + NNLA 50 mg/kg; hypoxia, no NNLA;
      hypoxia + NNLA 25 mg/kg; hypoxia + NNLA 50 mg/kg). One hour after the start of
      NNLA or saline infusion, hypoxia was induced by lowering the FiO2 to 0.07 in the
      three hypoxia groups, whereas in the three other groups normoxia was maintained.
      After 60 min of hypoxia, the brain was taken out and frozen. NOS activity, Na+,K+
      ATPase activity, conjugated dienes, and [3H]MK-801 binding to the NMDA receptor
      of cerebral cortical tissue were determined. NOS activity was reduced to 34% of
      its baseline value with NNLA 25 mg/kg, and to 19-27% of its baseline value with
      NNLA 50 mg/kg, respectively. Administration of NNLA did neither significantly
      alter the hypoxia-induced production of conjugated dienes, indicating lipid
      peroxidation nor the decrease of Na+,K+-ATPase activity after hypoxia. [3H]MK-801
      binding studies of the NMDA receptor, however, showed that NNLA preserved Bmax
      and Kd after hypoxia. We conclude that inhibition of NOS does not change the
      hypoxia-induced decrease of Na+,K+-ATPase activity and production of conjugated
      dienes in brain cell membranes. Inhibition of NOS preserved the binding of [3H]MK
      801 to the NMDA receptor after hypoxia.

PMID- 9262220
TI  - Ischemia-reperfusion injury in the intestines of newborn pigs.
AB  - Although the pathogenesis of necrotizing enterocolitis remains uncertain,
      ischemia appears to be an important contributing factor to the development of
      this disorder. Reperfusion plays a major role in ischemia-related injury, and
      oxygen free radicals produced during reperfusion most likely contribute to the
      injury. These oxidants can be generated during prostanoid metabolism, which
      increases during reperfusion of ischemic gut in adult subjects. The present study
      was designed to: 1) examine the effects of superior mesenteric artery occlusion,
      e.g. ischemia and reperfusion in vivo on the development of histopathologic
      intestinal injury; 2) determine whether products of arachidonic acid metabolism,
      e.g. prostanoids are increased during reperfusion of ischemic gut; and 3)
      determine whether oxygen free radical scavengers attenuate the injury in newborn
      pigs. Chronically catheterized placebo-pretreated newborn pigs exposed to
      ischemia-reperfusion, placebo-pretreated nonischemic control pigs, and
      polyethylene glycol-superoxide dismutase (SOD) plus polyethylene glycol-catalase
      (CAT)-pretreated, ischemic pigs were studied by examining changes in intestinal
      circulation, oxygenation, prostanoids, and tissue injury. In the placebo
      pretreated pigs, intestinal blood flow decreased to very low levels during
      superior mesenteric artery occlusion. During reperfusion, blood flow increased,
      but remained below baseline. After ischemia, oxygen uptake returned to values
      that were similar to baseline. Intestinal efflux of the vasodilator 6-keto
      prostaglandin F1alpha was evident (p < 0.05 versus no or zero efflux) during
      early reperfusion. Histopathologic scoring of terminal ileal samples showed
      significant mucosal necrosis, surface epithelial disruption, lamina propria
      congestion and hemorrhage, submucosal hemorrhage, edema, and increases in cells
      compared with the placebo-pretreated nonischemic pigs. In the SOD plus CAT
      pretreated ischemic pigs, changes in intestinal blood flow, oxygen uptake, 6-keto
      prostaglandin F1alpha efflux, and the pattern of the ileal tissue injury did not
      differ significantly from the placebo-pretreated ischemic pigs. In summary,
      superior mesenteric artery occlusion for 1 h and reperfusion for 2 h resulted in
      severe intestinal ischemia, early postocclusive limited increases in intestinal
      perfusion and oxygen uptake, efflux of vasodilating prostanoids during early
      reperfusion, and signs of ischemic tissue injury in the placebo- and SOD plus CAT
      pretreated pigs. This study demonstrates that, after superior mesenteric artery
      occlusion and reperfusion, severe intestinal tissue injury is detected in vivo,
      prostanoid efflux increases, and SOD plus CAT given just before occlusion does
      not attenuate the extent of injury in newborn pigs.

PMID- 9262221
TI  - Fetal and neonatal expression of the apical sodium-dependent bile acid
      transporter in the rat ileum and kidney.
AB  - Previous investigations in rats older than 7 d have shown that apical sodium
      dependent bile acid transport in the ileum is abruptly expressed at the time of
      weaning, whereas it is constitutively expressed in the kidney. The current study
      was designed to characterize the expression of sodium-dependent bile acid
      transport in late gestation and in the immediate postnatal period in the rat.
      Sodium-dependent bile acid transport was measured by rapid filtration using
      [3H]taurocholate and crude brush border membrane vesicles. Apical sodium
      dependent bile acid transporter (ASBT) and ileal lipid binding protein (ILBP)
      expression were analyzed by Western and Northern blotting. Ileal bile acid
      content was measured by gas chromatography/mass spectrometry. In the ileum
      significantly greater sodium-dependent taurocholate uptake was measured in fetal
      d 22 (E22) membrane vesicles compared with postnatal d 7 (E22 17.0 +/- 5.7. P7
      3.9 +/- 2.1 pmol/mg/60 s mean +/- SD, n = 3, p = 0.02). Gas chromatography/mass
      spectrometry revealed significant quantities of ileal bile acids at E22. Western
      and northern blotting of fetal ileum revealed ASBT but not ILBP. ASBT expression
      was suppressed by P7 and then reinduced by P21, whereas ILBP appeared to be first
      expressed postnatally. In contrast ASBT expression in the kidney was less age
      dependent. Therefore, it appears that functional expression of the ASBT gene in
      the rat ileum is biphasic with a prenatal onset of expression, followed by
      repression in the early postnatal period and then marked reinduction at weaning.

PMID- 9262222
TI  - Intestinal excretion of unconjugated bilirubin in man and rats with inherited
      unconjugated hyperbilirubinemia.
AB  - Patients with Crigler-Najjar syndrome and Gunn rats cannot form bilirubin
      glucuronides owing to a lack of bilirubin UDP-glucuronosyltransferase activity.
      Because increased serum and tissue bilirubin levels remain constant, an
      alternative excretory route has to substitute for this deficiency. Gunn rats
      excrete in bile only 2-13% of the bilirubins eliminated in Wistar rats. In
      contrast, the biliary excretion rate of urobilinogen in Gunn and Wistar rats is
      comparable. The sum of bilirubins and urobilinogen excreted in the bile of Gunn
      rats amounts to 10-30% of pigments excreted in Wistar rats. Despite this low
      biliary excretion, the intestinal content and fecal excretion of bile pigments in
      Gunn and Wistar rats were similar. These data support an extrabiliary entrance of
      unconjugated bilirubin into the intestine. Additional proof for this was found in
      that the intestinal lumen of Gunn rats still contains a high amount of bilirubins
      and urobilinogen after 3 d of external biliary drainage. A similar procedure in
      Wistar rats resulted in the complete disappearance of bile pigments from the
      intestine. The direct transmural transport of bilirubin from blood to all parts
      of the intestinal lumen was demonstrated by injecting 14C-bilirubin i.v. into
      Gunn rats with isolated parts of small and large intestine. In Crigler-Najjar and
      Gilbert's syndrome patients, the biliary excretion of bile pigments has
      previously been shown to be strongly reduced. Their stools, however, contained
      approximately the same amount of bile pigments as in normal subjects. Although
      only traces of unconjugated bilirubin were detected in the stool of normal
      persons (4 +/- 3% of total bile pigments), higher amounts were found in patients
      with Crigler-Najjar disease (20 +/- 12&). These results suggest a direct
      intestinal permeation of unconjugated bilirubin in severe unconjugated
      hyperbilirubinemia both in man and rats.

PMID- 9262223
TI  - Exogenous insulin-like growth factor-I increases weight gain in intrauterine
      growth-retarded neonatal pigs.
AB  - Many cases of intrauterine growth retardation (IUGR) are the result of placental
      insufficiency, suggesting that potential therapies should focus on the neonate
      rather than the pregnant female. We wished to determine whether IGF-I could be
      used therapeutically to stimulate normal rates of growth in these neonates. Eight
      sows received 2.3 kg/d of either a control (13% protein) or protein-restricted
      (0.5% protein) diet from d 63 of pregnancy to parturition. Litters were reduced
      to 6 pigs at 3 d of age, and IUGR neonates were fostered onto a control sow.
      Three pigs/ litter received an osmotic minipump containing either saline or
      recombinant human IGF-I, delivered at 4 microg/h from d 3 to d 10 of age. Tissue
      protein synthesis was measured in all pigs using a flooding dose of
      [3H]phenylalanine. At birth, both body weight (10%) and circulating IGF-I
      concentration (30%) were significantly lower in IUGR than in control newborns.
      The infusion of IGF-I to IUGR neonates significantly increased the circulating
      concentration of IGF-I, growth rate, and protein and fat accretion to control
      levels. The infusion of IGF-I did not alter concentrations of insulin, glucose,
      IGF-II, or the thyroid hormones. Our results suggest that IGF-I may be a
      potential therapy to restore normal growth in IUGR infants.

PMID- 9262224
TI  - Zinc and intestinal anaphylaxis to cow's milk proteins in malnourished guinea
      pigs.
AB  - Zinc supplementation could favor recovery from diarrhea in malnourished children.
      As the recent experimental evidence suggests that oxidative stress and intestinal
      anaphylaxis may contribute to the intestinal dysfunction associated with
      malnutrition, we postulated that zinc could act through antioxidant or
      antianaphylactic properties. Control (C), malnourished (M), and malnourished zinc
      treated (MZ) guinea pigs were, respectively, fed a normal 30% protein diet, a low
      4% protein diet, and a low 4% protein diet plus 1800 ppm of zinc. Milk proteins
      were included in the diets to trigger intestinal anaphylaxis. Milk sensitization
      was assessed by passive cutaneous anaphylaxis (PCA) against beta-lactoglobulin
      and by intestinal anaphylaxis measured in Ussing chambers by the increase in
      short circuit-current after addition of beta-lactoglobulin (deltaIsc(betaLg)).
      Oxidative stress was assessed by intestinal lipid peroxidation. The intestinal
      secretion was assessed by deltaIsc induced by inflammatory mediators.
      Malnutrition increased the level of anti-betaLg reaginic antibodies [PCA = 1.19
      +/- 0.79 and 0.69 +/- 0.67 log(l/titer) in M versus C guinea pigs, p = 0.07] and
      enhanced intestinal anaphylaxis (deltaIsc(betaLg)) = 16.4 +/- 9.9 and 9.1 +/- 5.8
      microA/cm2 in M versus C guinea pigs, p = 0.07), without inducing intestinal
      lipid peroxidation. Moreover, malnutrition enhanced significantly the intestinal
      secretory response to histamine and 5-hydroxytryptamine. Administration of
      pharmacologic doses of zinc during malnutrition inhibited the increase in milk
      sensitization induced by malnutrition, both at the systemic [PCA = 0.35 +/- 0.55
      log(l/titer) in MZ guinea pigs, p = 0.03 versus M] and intestinal
      (deltaIsc(betaLg)) = 2.8 +/- 2.5 microA/cm2 in MZ guinea pigs; p = 0.001 versus
      M) level, and prevented the hypersecretion in response to histamine and 5
      hydroxytryptamine. These data suggest that zinc has antianaphylactic and
      antisecretory properties that may contribute to its capacity to prevent
      intestinal dysfunction during malnutrition.

PMID- 9262225
TI  - The mechanisms of transient hypothyroxinemia in infants born to mothers with
      Graves' disease.
AB  - Transient hypothyroxinemia in infants born to mothers with Graves' disease is a
      unique disorder first reported by us in 1988. Most mothers of these infants have
      had no treatment, are diagnosed as having thyrotoxicosis during the last
      trimester, or were not well controlled during pregnancy. These infants are
      believed to have transient central hypothyroidism, the mechanisms of which have
      not been elucidated. We measured TSH-receptor antibody activities in maternal
      serum and blood thyroxine (T4) (free thyroxine, FT4) and TSH levels in blood
      dried on filter paper at 1, 3, and 5 d of age in 114 infants born to mothers with
      Graves' disease. The 114 infants were retrospectively divided into three groups
      according to the clinical course and thyroid function data: group G, neonatal
      thyrotoxicosis; group T, transient hypothyroxinemia; and group E, euthyroid. In
      group T, the dried blood T4 (FT4) level from cord blood and/or 1 d of age blood
      was 6.0 +/- 2.3 microg/dL (0.92 +/- 0.52 ng/dL), a value significantly higher
      than that at 5 d of age (3.6 +/- 1.0 microg/dL; 0.38 +/- 0.18 ng/dL) (p = 0.025
      in T4, p = 0.042 in FT4). In contrast, these levels were significantly lower at
      birth relative to 5 d in group G (p = 0.0001 in T4) and not significantly changed
      in group E. The TSH level of cord blood and/or 1-d-old blood in group T was
      significantly lower than that of group E (p = 0.0006). Moreover, the TSH levels
      in response to thyrotropin-releasing hormone were blunted in most infants in
      group T. Bone maturation was not delayed in group T, compared with euthyroid
      infants. The higher blood T4 (FT4) levels at birth, relative to 5 d in group T,
      suggested that the fetal T4 level was higher than that of the newborn period. The
      fetal T4 level might have been elevated owing to transfer of T4 from mother to
      fetus during the last trimester when the mother's thyroid function was elevated
      and consequently the fetal pituitary-thyroid axis was suppressed. Although the
      serum T4 (FT4) levels were decreased after birth, TSH levels were not elevated,
      probably because the pituitary-thyroid axis was suppressed. This may be the
      reason for the transient hypothyroxinemia with a normal TSH level in infants born
      to mothers with poorly controlled Graves' disease. Weak maternal thyroid
      stimulating antibody activities and differences in sensitivity of the thyroid
      gland to TSH-receptor antibodies may contribute to this unique disorder.

PMID- 9262226
TI  - A case of hyperzincemia with functional zinc depletion: a new disorder?
AB  - We report the case of an 1l-y-old boy with a plasma Zn concentration greater than
      200 micromol/L, but with symptoms consistent with Zn deficiency. He has had
      hepatosplenomegaly, rashes, stunted growth (<3rd centile), anemia, and impaired
      immune function since infancy. He also has vasculitis and osteoporosis. A plasma
      Zn-binding protein has been separated and characterized by a combination of size
      exclusion and ion exchange chromatography and electrophoretic studies and by
      immunologic methods. Antibodies to the partially purified protein have been
      raised in rabbits. Size exclusion chromatography shows that Zn is bound to a
      protein with a mass 110000-300000 kD. Electrophoretic and mass spectrometry
      studies suggest that the protein may be composed of several subunits. One
      component of the isolated protein reacts with antiserum to alpha2-macroglobulin;
      immunoprecipitation studies confirm that the protein is not alpha2-macroglobulin
      or a histidine-rich glycoprotein. Kinetic studies of zinc metabolism in the
      patient and his mother with stable Zn isotopes show the presence of increased
      exchangeable Zn, with a rapid flux from plasma to a stable pool. Liver and muscle
      Zn and Cu concentrations are raised, but with no abnormal liver histology.
      Immunoreactive metallothionein in the liver is increased. We suggest that this
      boy may suffer from a previously unrecognized inborn error of Zn metabolism
      causing symptomatic zinc deficiency.

PMID- 9262227
TI  - Examination of telomere lengths in muscle tissue casts doubt on replicative aging
      as cause of progression in Duchenne muscular dystrophy.
AB  - The mean telomere length (TL) of somatic cells indicates their replicative age.
      In comparison with normal leukocytes (-0.03 kbp/y, 6.2 kbp at 80 y), we found
      advanced TL shortening in premature aging due to ataxia-telangiectasia or the
      Nijmegen chromosomal breakage syndrome. Duchenne muscular dystrophy (DMD) has
      been related to replicative senescence of satellite cells (SCs) caused by
      increased fiber turnover. Therefore, we determined TLs in DMD muscle. Because the
      regenerated fiber nuclei are produced by SCs. telomeres of both fiber and SC
      nuclei should be shortened. In DMD the SC number is increased. We determined that
      up to the age of 7 y the sum of fiber and SC nuclei should be large enough (73%)
      for the detection of TL shortening. Normal muscle fibers have negligible turnover
      rates, and, as expected, we did not find age-related TL shortening (10-83 y, n =
      24, 8.3 +/- 0.5 kbp). Surprisingly, there was only slight TL shortening in
      patient muscles (DMD, 0.3-4.8 y, n = 4, 8.3 +/- 0.7 kbp; 5-7 y, n = 7, 7.9 +/-
      0.4 kbp; limb-girdle muscular dystrophy 2C, 13 y, 7.6 kbp; Becker muscular
      dystrophy, 7 y, 8.5 kbp). Similarly, the peak positions of the telomere blots
      varied only slightly (DMD, 10.0 +/- 0.9 kbp; normal: 10.7 +/- 0.9 kbp). In
      accordance with our TL findings we derived less than 4 annual doublings per SC
      from published histologic data on DMD.

PMID- 9262228
TI  - The presence and significance of the Pi class glutathione S-transferase isoenzyme
      in cerebrospinal fluid during the course of meningitis in children.
AB  - A rise in the concentration of the Pi class isoenzyme of glutathione S
      transferase (GST) in the cerebrospinal fluid (CSF) during meningitis may be an
      early indicator of inflammation and cell damage. Pi class GST concentrations were
      measured in 48 samples of CSF from 46 children with proven or suspected
      meningitis using a commercially available immunoassay. Forty-four fetal brain
      samples were assayed by isoelectric focusing to determine the nature and number
      of isoenzymes likely to be released. Twenty-four percent of children had
      measurable amounts of the isoenzyme in their CSF during the initial stages of the
      disease. One child, for whom CSF samples were taken pre-, mid-, and post
      antibiotic treatment, had measurable Pi class GST in the CSF only in the mid
      treatment sample, when bacterial lysis and inflammation are likely to be at their
      peak. Where follow-up data were available, two of three children with measurable
      Pi class GST in their CSF at the initial stages had recordable disabilities at 5
      y of age compared with 4 of 11 of those in whom no Pi class GST was detected. Two
      proteins analogous to Pi class GST were detected in frozen brain tissue, but only
      one was active with a known substrate; only the active protein was seen in fresh
      tissue. We conclude that 1) initial high levels of CSF Pi class GST may be an
      indicator of the severity of inflammation and thus of prognostic significance and
      2) only one Pi class GST occurs in brain tissue.

PMID- 9262229
TI  - Cytokine production differs in children and adults.
AB  - The susceptibility of normal, healthy children to infection has long been
      recognized, but the underlying mechanisms are poorly understood. As adequate
      cytokine production is crucial for optimal immune responses, we assessed antigen
      and mitogen-induced cytokine production in healthy children. Our results
      demonstrate that healthy children differ markedly compared with adults in their
      ability to produce cytokines (IL-2, interferon-gamma, IL-4, and IL-6). Maximal
      stimulation with mitogen demonstrated impaired cytokine production with markedly
      lower levels of all four cytokines produced compared with adult levels. When
      stimulated with antigens, median levels of IL-2 and IL-4 remained lower than
      adult values, IL-6 production was increased as was interferon-gamma, albeit not
      significantly. Although the study was carried out on peripheral blood mononuclear
      cells that represent a restricted compartment of the immune system, these data
      suggest that, in healthy children, cytokine production is decreased and/or
      altered and could result in a suboptimal immune response, which could be one of
      the factors underlying increased susceptibility to infection in children.

PMID- 9262230
TI  - Prostanoid biosynthesis by blood monocytes of children with hyperprostaglandin E
      syndrome.
AB  - Hyperprostaglandin E syndrome (HPS), the prenatal variant of Bartter's syndrome,
      is characterized by a marked and selective stimulation of prostaglandin E (PGE2)
      synthesis. In the study group HPS patients showed increased urinary levels of
      PGE2, an index of renal, and of 11 alpha-hydroxy-9,15-dioxo-2,3,4,5,20-pentanor
      19-carboxyprostano ic acid (PGE-M), an index of systemic PGE2 synthesis of 470%
      and of 570%, respectively. In addition, plasma concentration of PGE-M was also
      elevated 6.3-fold when compared with a control group. The urinary levels of other
      prostanoids were unaltered. During indomethacin treatment in both groups
      prostanoid excretion rates were suppressed to similar levels. To investigate the
      origin of stimulated prostanoid biosynthesis in HPS patients CD14+ monocytes were
      isolated from plasma samples, and the prostanoid synthesis was analyzed. The
      pattern and amounts of metabolites synthesized from endogenous arachidonic acid
      pools did not vary significantly between monocytes of the HPS and the control
      group. Thromboxane A2 (TXA2) was formed as the major prostanoid product. Using
      PGH2 as an exogenous substrate, again no difference in PGE2 biosynthesis was
      observed, indicating no difference in PGE-synthetic activity between both groups.
      Additionally, mRNA expression analysis of CD14+ monocytes via RT-PCR delineated
      the constitutive expression of cyclooxygenase-1, cyclooxygenase-2, and
      thromboxane synthase mRNA in cells from HPS patients and controls without
      statistical differences between these two groups. In conclusion, our data show
      that monocytes are not the source for the increased PGE2 biosynthesis in children
      with HPS, and a genetic defect in PGE synthesis can be excluded as the primary
      event in the pathogenesis in HPS.

PMID- 9262231
TI  - Analysis of the hypervariable region of hepatitis C virus E2/NS1 gene in an
      infant infected by blood transfusion.
AB  - We investigated the sequential change in the hypervariable region 1 (HVR 1) of
      hepatitis C virus (HCV) E2/NS1 gene in an infant. He was transfused with 160 mL
      of blood containing the HCV (0.7 Meq/mL) on the 6th d after birth and
      subsequently developed chronic viremia. At 16 mo, the HVR1 amino acid sequences
      of HCV observed in the infant's sera were very similar to those from the donor
      (his maternal grandfather) on the day of transfusion. However, highly variable
      amino acid sequences of HVR1 were observed throughout infancy. These results
      demonstrate that an adaptive response of HCV to evade host immunity seems to
      occur, as in adult cases, even in early infancy when the ability to produce
      humoral immunoglobulin is thought to be low.

PMID- 9262232
TI  - Glutamine synthetase is a glial-specific marker in the olfactory regions of the
      lobster (Panulirus argus) nervous system.
AB  - Glutamine synthetase (GS) has been qualified as a very specific marker of
      astroglial-type neuroglia in vertebrate neural tissues. In this paper we have
      begun to examine the possibility that glial localization of GS could be a
      ubiquitous characteristic of complex nervous systems. To this end we have used
      immunohistochemistry to localize GS-like immunoreactivity in the olfactory
      regions of the complex nervous system of the arthropod, the spiny lobster
      Panulirus argus. We describe a novel method for affinity isolation of antibodies
      from crude serum. Using this approach we purified GS-specific antibodies to chick
      retina GS and used these to analyze the lobster brain and the primary olfactory
      organ. Western blots showed that the lobster brain contains an immunoreactive
      peptide with nearly the same molecular mass as that of chick retina GS. Northern
      blot analyses of mRNA and enzymatic activity assays also confirm that the lobster
      brain produces GS. Immunohistochemical staining of sectioned lobster olfactory
      lobes and sensory sensilla showed strong reactivity in specific cells. Comparison
      of the GS immunostaining pattern with that for FMRFamide, a well characterized
      marker of neurons in invertebrate neural tissues, it became clear that GS is
      indeed glial-specific in lobster neural tissues as it is in vertebrates. These
      results suggest that the compartmentalization of GS in non-neuronal cells is
      either an early step in neural evolution or is an obligate and fundamental
      characteristic of complex neural systems composed of both neurons and neuroglia.

PMID- 9262233
TI  - Analysis of motile oligodendrocyte precursor cells in vitro and in brain slices.
AB  - Oligodendrocyte precursor cells are purported to migrate over long distances into
      the various brain regions where they differentiate into oligodendrocytes and
      fulfill their appropriate tasks, i.e., myelination of axons. Here we characterize
      motile oligodendrocyte precursor cells in detail. Video-time lapse analysis was
      performed on isolated precursor cells in single cell cultures, in co-culture with
      cerebellar microexplants, and in living brain slices. Motility analysis of
      individual cells was combined with electrophysiological, immunological, and
      morphological characterizations. Translocation of the cell bodies was not
      continuous but occurred in waves. All motile cells exhibited a simple morphology
      and most, but not all, of them expressed the A2B5 epitope in vitro. Patch clamp
      analysis of the motile cells confirmed that they belong to the O-2A lineage. The
      percentage of motile cells, as well as their velocities, were enhanced on
      substrate-coated laminin in comparison to poly-L-lysine. Motility was not
      influenced by the presence of cerebellar microexplants. O-2A progenitor cells did
      not migrate strictly along neurite fascicles which were projected from the
      microexplants. Glial progenitor cells in situ also did not strictly migrate along
      the main direction of the axonal fibers of the corpus callosum but rather
      traversed the fibers with an overall direction toward the cortex. After Lucifer
      Yellow filling of the motile progenitor cells in situ, we could demonstrate that
      they were dye-coupled to yet unidentified cells of the corpus callosum.

PMID- 9262234
TI  - Gap junctions equalize intracellular Na+ concentration in astrocytes.
AB  - Gap junctions between glial cells allow intercellular exchange of ions and small
      molecules. We have investigated the influence of gap junction coupling on
      regulation of intracellular Na+ concentration ([Na+]i) in cultured rat
      hippocampal astrocytes, using fluorescence ratio imaging with the Na+ indicator
      dye SBFI (sodium-binding benzofuran isophthalate). The [Na+]i in neighboring
      astrocytes was very similar (12.0 +/- 3.3 mM) and did not fluctuate under resting
      conditions. During uncoupling of gap junctions with octanol (0.5 mM), baseline
      [Na+]i was unaltered in 24%, increased in 54%, and decreased in 22% of cells.
      Qualitatively similar results were obtained with two other uncoupling agents,
      heptanol and alpha-glycyrrhetinic acid (AGA). Octanol did not alter the recovery
      from intracellular Na+ load induced by removal of extracellular K+, indicating
      that octanol's effects on baseline [Na+]i were not due to inhibition of Na+, K+
      ATPase activity. Under control conditions, increasing [K+]o from 3 to 8 mM caused
      similar decreases in [Na+]i in groups of astrocytes, presumably by stimulating
      Na+, K+-ATPase. During octanol application, [K+]o-induced [Na+]i decreases were
      amplified in cells with increased baseline [Na+]i, and reduced in cells with
      decreased baseline [Na+]i. This suggests that baseline [Na+]i in astrocytes
      "sets" the responsiveness of Na+, K+-ATPase to increases in [K]o. Our results
      indicate that individual hippocampal astrocytes in culture rapidly develop
      different levels of baseline [Na+]i when they are isolated from one another by
      uncoupling agents. In astrocytes, therefore, an apparent function of coupling is
      the intercellular exchange of Na+ ions to equalize baseline [Na+]i, which serves
      to coordinate physiological responses that depend on the intracellular
      concentration of this ion.

PMID- 9262235
TI  - Dibutyryl cyclic AMP and inflammatory cytokines mediate C3 expression in Schwann
      cells.
AB  - Schwann cells (SchC), the myelinating glia of the peripheral nervous system, are
      immunocompetent cells and secrete a variety of immune and inflammatory mediators.
      In this report, we show that rat SchC in vitro express both C3 mRNA and protein
      in response to dibutyryl cyclic AMP (dbcAMP) and the cytokines IFN-gamma, TNF
      alpha, and IL-1beta. SchC in culture constitutively expressed low levels of C3
      which were significantly upregulated upon stimulation with 1mM dbcAMP by 24
      hours, and persisted up to 120 hours. This response was minimally enhanced by
      costimulation with 100 U/ml IFN-gamma, whereas costimulation with 100 U/ml IFN
      gamma together with 150-450 ng/ml TNF-alpha induced a greatly increased C3
      response. TNF-alpha alone did not induce C3 expression in SchC. Cycloheximide
      inhibited this dbcAMP-dependent delayed C3 production, thus implying an
      intermediary signal in the induction pathway requiring protein synthesis.
      Treatment with 0.1-10 ng/ml IL-1beta for 0-72 hours induced C3 mRNA and protein
      in a dose-dependent manner. C3 mRNA was detectable at 1 hour and mRNA and protein
      peaked by 6-12 hours on stimulation with 10 ng/ml IL-1beta, or at 48 hours with
      1.0 ng/ml IL-1beta. Furthermore, IL-1beta mRNA was detected at 6 hours in dbcAMP
      treated SchC, preceding the dbcAMP-induced C3 expression by 18 hours. Induction
      of C3 mRNA and protein by dbcAMP at 24 hours was inhibited >85% by a neutralizing
      anti-IL-1beta antibody and 76% with an IL-1 receptor antagonist. This suggests
      that dbcAMP-induced synthesis of IL-1beta mediates the C3 production by SchC in
      an autocrine/paracrine fashion by binding to a functional IL-1 receptor expressed
      on the surface of SchC. Endoneurial IL-1 and C3 production by SchC may therefore
      contribute to the inflammatory events associated with peripheral nerve
      demyelination.

PMID- 9262236
TI  - Phenotypic severity of murine Plp mutants reflects in vivo and in vitro
      variations in transport of PLP isoproteins.
AB  - Mutations of the major myelin gene, proteolipid protein (Plp), cause Pelizaeus
      Merzbacher disease and some forms of spastic paraplegia in man and dysmyelinating
      phenotypes in animals. The clinical severity is markedly heterogeneous, ranging
      from relatively mild to severe and fatal. Point mutations, or frame shifts, which
      are predicted to result in translation of structurally altered proteins account
      for many of these cases, including 3 of the allelic murine conditions. Plp(jp
      rsh), Plp(jp-msd), and Plp(jp) represent an increasing severity of clinical and
      pathological phenotypes, respectively. In this study we determined whether there
      was any correlation between the severity of phenotype and the transport of the
      predicted abnormal protein. We examined the ability of the two products of the
      Plp gene, PLP and DM20, to insert into the plasma membrane of transfected BHK or
      COS-7 cells, and into the myelin sheath of oligodendrocytes. With these
      complementary in vitro and in vivo approaches we find that proteins of Plp(jp
      rsh), associated with the mildest phenotype, have a far greater ability to insert
      into the cell membrane or myelin than those associated with the severe
      phenotypes. Additionally, altered DM20 is more readily transported to the cell
      surface and to myelin than the PLP isoprotein. Interestingly, the two clonal cell
      lines chosen for transient transfection differ in their ability to fold DM20 from
      Plp(jp-rsh) and Plp(jp-msd) mice correctly, as inferred by staining for the
      conformation-sensitive O10 epitope. In the case of Plp(jp), which is associated
      with the most severe phenotype, no PLP or O10 staining is present at the cell
      surface or in myelin. The perturbation in trafficking observed for altered
      Plp(jp) PLP and DM20 in oligodendrocytes does not extend to other myelin membrane
      proteins, such as MAG and MOG, nor to wild type PLP co-expressed in the same
      cell, all of which are correctly inserted into myelin. As Plp-knockout mice do
      not have a dysmyelinating phenotype it seems unlikely that absence of PLP and/or
      DM20 in the membrane is responsible for the pathology. It remains to be
      determined whether the perturbation in protein trafficking is associated with the
      dysmyelination, or if the altered product of the mutant alleles acquire a novel
      function which is deleterious to myelin production by oligodendrocytes.

PMID- 9262237
TI  - Effects of delayed re-innervation on the expression of c-erbB receptors by
      chronically denervated rat Schwann cells in vivo.
AB  - We propose that chronically denervated Schwann cells may be less able to respond
      to axonal signals than their acutely denervated counterparts, and that this lack
      of sensitivity may be one reason why axons fail to regenerate into chronically
      denervated nerve stumps. To test this proposal we have used in situ
      hybridization, and quantitative and qualitative immunohistochemistry to compare
      the expression of c-erbB2 and c-erbB4 receptors in Schwann cells denervated for
      up to 6 months in vivo, with that seen in Schwann cells denervated for similar
      periods of time but then exposed to regenerating axons. The results were
      correlated with the extent of axonal regeneration in each experimental group as
      assessed from transverse sections which had been double-immunolabelled using anti
      S-100 and anti-beta tubulin III antibodies. Since c-erbBs are receptors for
      neuronally derived neuregulins we probed the appropriate axotomised DRG neurons
      for expression of GGF2 mRNA. When the denervated distal stumps were anastomosed
      to acutely transected proximal stumps, GGF expression in DRGs increased
      transiently during the first week: we assume that secreted GGF2 derived from
      regrowing axon sprouts would have been available to Schwann cells in all distal
      stumps. Endoneurial cell proliferation (predominantly Schwann cell
      proliferation); levels of expression of c-erbB receptors by Schwann cells, and
      the degree to which axons regenerated into the distal stumps all decreased as the
      period of prior denervation increased: the longer the time of denervation, the
      lower the expression of c-erbBs in Schwann cells, and the smaller the percentage
      of bands of Bungner which were re-innervated.

PMID- 9262238
TI  - Characterization of focal adhesion assembly in XR1 glial cells.
AB  - In the present communication, we have characterized focal adhesions in cultured
      glial cells derived from the Xenopus retina. Using antibodies directed against
      focal adhesion proteins we found that beta1 integrin immunoreactivity colocalized
      with talin, vinculin, and phosphotyrosine immunoreactivities in glial cells from
      primary cultures of Xenopus retina, as well as in the XR1 glial cell line, an
      immortal cell line derived from Xenopus retinal neuroepithelium. beta1 integrin
      immunoreactivity also colocalized with the termini of rhodamine phalloidin
      labeled filamentous-actin at focal adhesions. The regulation of focal adhesion
      assembly was examined in XR1 glial cells using inhibitors against actin
      polymerization (cytochalasins) or tyrosine kinase activity (genistein). Compared
      to control cultures, those treated with the inhibitors exhibited a dose-dependent
      decrease in the proportion of cells displaying focal adhesions. Treatment with
      cytochalasin B also resulted in a dose-dependent decrease in cell area. Mature
      focal adhesions in XR1 cells with a flattened, spread morphology also were
      disrupted by the presence of these inhibitors. These results provide strong
      evidence that an intact actin cytoskeleton and tyrosine kinase activity regulate
      focal adhesion assembly and also play important roles in the maintenance of the
      integrity of focal adhesions in glial cells.

PMID- 9262239
TI  - Localization of endothelial-monocyte-activating polypeptide II (EMAP II), a novel
      proinflammatory cytokine, to lesions of experimental autoimmune
      encephalomyelitis, neuritis and uveitis: expression by monocytes and activated
      microglial cells.
AB  - Endothelial-Monocyte-Activating Polypeptide II (EMAP II) is a proinflammatory
      cytokine and chemoattractant of macrophages. In order to investigate the role of
      EMAP II in autoimmune lesions of the rat nervous system, we have used a synthetic
      gene to express EMAP II in E. coli and have produced monoclonal antibodies
      against EMAP II. Monoclonal antibodies are suited to demonstrate EMAP II in
      ELISAs, Western blots, and paraffin-embedded tissue sections. EMAP II was
      localized to monocytes/macrophages with rather selective staining of a minor rat
      monocyte subpopulation of lymphoid tissues such as spleen, lymph nodes or
      follicles of the gut. In the normal brain, cells of the perivascular but not
      parenchymal microglia were stained. We then investigated expression of EMAP II
      during experimental autoimmune encephalomyelitis (EAE), neuritis (EAN), and
      uveitis (EAU). Within the local inflammatory lesions infiltrating macrophages are
      prominently stained. In the diseased brain, EMAP II-positive microglial cells are
      not only found in the direct vicinity of the inflammatory infiltrate, but
      widespread activation is seen in the parenchyma. This is the first demonstration
      that EMAP II is present in autoimmune lesions. Immunostaining of microglial cells
      is noteworthy, as these cells are strategically placed regulatory elements of CNS
      immunosurveillance. EMAP II might be a factor regulating monocyte
      chemoattraction, endothelial cell activation and a regulator of microglial cell
      reactivity in autoimmune inflammation of the central nervous system.

PMID- 9262240
TI  - Hormone replacement therapy and endometrial cancer: are current regimens safe?

PMID- 9262241
TI  - Malignant origin of the stromal component of Wilms' tumor.

PMID- 9262242
TI  - Doctors strive to minimize DCIS treatment.

PMID- 9262243
TI  - New clinical trials under way for DCIS.

PMID- 9262244
TI  - Calculating the coordinates of cancer risk: no "walk-in" assays just yet.

PMID- 9262245
TI  - National Cancer Policy Board adds its voice to tobacco issues.

PMID- 9262246
TI  - Congress adjourns: major cancer program actions in the works.

PMID- 9262247
TI  - Developmental genes and cancer: role of patched in basal cell carcinoma of the
      skin.
AB  - Many genes originally identified because of their role in embryonic development
      are also important in postnatal control of cell growth and differentiation.
      Mutations in some of these genes have been shown to cause cancer. Basal cell
      carcinoma (BCC) of the skin is the most common cancer in humans. More than 750000
      new cases are diagnosed annually, and the incidence is rising. BCCs are slow
      growing, locally invasive tumors that rarely metastasize but can result in
      extensive morbidity through local recurrence and tissue destruction.
      Epidemiologic studies suggest that sunlight (particularly UVB radiation) is a
      strong risk factor for BCC formation, although other factors are also involved.
      The nevoid basal cell carcinoma syndrome (NBCCS), a rare genetic disorder, is
      characterized by predisposition to BCCs and other tumors as well as to a wide
      range of developmental defects. NBCCS maps to chromosome 9q22.3, and loss of
      heterozygosity at this site in both sporadic and hereditary BCCs suggests that it
      functions as a tumor suppressor. The gene for NBCCS was recently cloned and is
      the human homologue of the Drosophila gene "patched." Genetic studies in
      Drosophila show that patched is part of the hedgehog signaling pathway, which is
      important in determining embryonic patterning and cell fate in multiple
      structures of the developing embryo. Human patched is mutated in both hereditary
      and sporadic BCCs, and inactivation of this gene is probably a necessary, if not
      sufficient, step for BCC formation. Delineation of the biochemical pathway in
      which patched functions may lead to rational medical therapy for BCCs and
      possibly for other tumors associated with NBCCS.

PMID- 9262248
TI  - Estrogen-progestin replacement therapy and endometrial cancer.
AB  - BACKGROUND: It has been known for more than 20 years that estrogen replacement
      therapy substantially increases a woman's risk of developing endometrial cancer.
      To reduce this increased risk, progestins have been added to estrogen replacement
      therapy for between 5 and 15 days (usually 7 or 10 days) per "month" in a
      sequential fashion (sequential estrogen-progestin replacement therapy) or with
      each dose of estrogen replacement therapy (continuous combined replacement
      therapy). At the present time, however, little is known about the effects of
      varying the number of days that progestin is used in sequential estrogen
      progestin replacement therapy. PURPOSE: We sought to determine the effects of
      sequential estrogen-progestin replacement therapy and continuous combined
      replacement therapy on a woman's risk of developing endometrial cancer. METHODS:
      A population-based, case-control study of 833 case subjects and 791 control
      subjects was conducted. Women were postmenopausal, white, and aged 50-74 years
      when first diagnosed with invasive endometrial cancer or were aged 50-74 years at
      the matching date for control subjects. All subjects were interviewed in person
      with the aid of a month-by-month calendar. Relative risks were estimated by odds
      ratios (ORs); ORs were adjusted simultaneously for the different forms of hormone
      replacement therapy and for the known endometrial cancer risk factors. RESULTS:
      The adjusted OR was 2.17 (95% confidence interval [CI] = 1.91-2.47) per 5 years
      of estrogen replacement therapy use (based on 422 users among the case subjects
      and 262 users among the control subjects). For women who received sequential
      estrogen-progestin replacement therapy with the progestin given for less than 10
      days (effectively 7 days) per month, the adjusted OR was only slightly reduced to
      1.87 (95% CI = 1.32-2.65) per 5 years of use (74 case subjects and 47 control
      subjects). However, when progestin was given for 10 or more days (effectively 10
      days), there was essentially no increased risk (adjusted OR = 1.07 per 5 years of
      use; 95% CI = 0.82-1.41) (79 case subjects and 88 control subjects). Continuous
      combined replacement therapy was also associated with essentially no increased
      risk (adjusted OR = 1.07 per 5 years of use; 95% CI = 0.80-1.43) (94 case
      subjects and 81 control subjects). CONCLUSIONS: The progestin in sequential
      estrogen-progestin replacement therapy needs to be given for at least 10 days to
      block effectively any increased risk of endometrial cancer. Continuous combined
      estrogen-progestin therapy is similarly effective. Neither regimen reduces a
      woman's underlying risk of endometrial cancer. The sharp distinction between the
      effects of less than 10 days (effectively 7 days) and 10 or more days
      (effectively 10 days) of progestin use in sequential estrogen-progestin
      replacement therapy suggests that the extent of endometrial sloughing may play a
      critical role in determining endometrial cancer risk.

PMID- 9262249
TI  - Patient-reported impotence and incontinence after nerve-sparing radical
      prostatectomy.
AB  - BACKGROUND: The age-adjusted rate of radical prostatectomy, the most common
      treatment of early (nonmetastatic) prostate cancer, increased almost sixfold
      between 1984 and 1990. This increase was due in part to reported improvements in
      postoperative sexual potency after the use of newly developed "nerve-sparing"
      procedures. However, published estimates from physicians of impotence following
      various types of radical prostatectomy may be low, since not all patients may
      report treatment-related complications accurately and completely to their
      doctors. In contrast, direct surveys of patients indicate much higher rates of
      postoperative sexual and urinary dysfunction. One problem with most physician and
      patient surveys is that they have been performed retrospectively, and
      pretreatment impotence and incontinence prevalent in older men cannot be assessed
      accurately in retrospective studies. PURPOSE: This study was initiated in a
      cohort of men before they underwent radical prostatectomy to assess treatment
      related effects on impotence and incontinence. METHODS: The study population
      consisted of 94 men enrolled in a cohort study of treatment for early prostate
      cancer. The patients completed questionnaires about sexual and urinary functions
      before surgery and at 3 and 12 months after surgery and had adequate information
      to assess the type of surgical technique used (non-nerve-sparing, unilateral
      nerve-sparing, or bilateral nerve-sparing). Because items assessing sexual
      function were inadvertently omitted from the questionnaire in the initial months
      of the study, information on sexual function for all time periods was available
      for only 49 men. RESULTS: Compared with men who had not been treated with a nerve
      sparing procedure, men who underwent nerve-sparing radical prostatectomy,
      particularly of the bilateral type, were younger and had better prognostic
      features, indicating less advanced cancers. Before surgery, nine (75%) of 12 men
      not treated with a nerve-sparing procedure reported erections that were usually
      inadequate for sexual intercourse compared with six (33%) of 18 men and one (5%)
      of 19 men who underwent unilateral and bilateral nerve-sparing prostatectomies,
      respectively. At 12 months after surgery, most men reported inadequate erections,
      including 15 (79%) of the 19 men who had bilateral nerve-sparing surgery;
      unilateral nerve preservation provided no apparent benefit. In general, nerve
      sparing surgery was associated with more use of absorbent pads at 3 and 12 months
      following treatment, and this approach was associated with substantial urinary
      incontinence at 3 months but not at 12 months following surgery. CONCLUSIONS:
      Nerve-sparing prostatectomy, particularly when performed unilaterally, improves
      postoperative sexual function to a lesser extent than previously reported.
      Because men with preoperative impotence and more advanced cancers receive nerve
      sparing surgery less often, some of the previously reported benefit of nerve
      preservation may be the result of patient selection and not of the technique per
      se.

PMID- 9262250
TI  - Dietary modulation of omega-3/omega-6 polyunsaturated fatty acid ratios in
      patients with breast cancer.
AB  - BACKGROUND: Polyunsaturated fatty acids of the omega-6 (omega-6) class, as found
      in corn and safflower oils, can act as precursors for intermediates involved in
      the growth of mammary tumors when fed to animals, whereas polyunsaturated fatty
      acids of the omega-3 (omega-3) class, as found in fish oil, can inhibit these
      effects. The effects of dietary intervention on the ratios of these fatty acids
      in breast and other adipose tissues have not previously been prospectively
      studied. PURPOSE: The present investigation was conducted to study the impact on
      the ratio of omega-3 and omega-6 polyunsaturated fatty acid in plasma and in
      adipose tissue of the breast and buttocks when women with breast cancer consume a
      low-fat diet and fish oil supplements. METHODS: Twenty-five women with high-risk
      localized breast cancer were enrolled in a dietary intervention program that
      required them to eat a low-fat diet and take a daily fish oil supplement
      throughout a 3-month period. Breast and gluteal fat biopsy specimens were
      obtained from each woman before and after dietary intervention. The fatty acid
      compositions of specimens of plasma, breast fat, and gluteal fat were determined
      by gas-liquid chromatography. Statistical analysis involved use of a two-sided
      paired t test. RESULTS: After dietary intervention, a reduction in the level of
      total omega-6 polyunsaturated fatty acids in the plasma was observed (P<.0003);
      moreover, total omega-3 polyunsaturated fatty acids increased approximately three
      fold (P<.0001) and the omega-3/omega-6 polyunsaturated fatty acids ratio
      increased approximately fourfold (i.e., mean values increased from 0.09 to 0.41;
      P = .0001). An increase in total omega-3 polyunsaturated fatty acids in breast
      adipose tissue was observed following dietary intervention (P = .04); the omega
      3/omega-6 polyunsaturated fatty acid ratio increased from a mean value of 0.05 to
      0.07 (P = .0001). An increase in total omega-3 polyunsaturated fatty acids was
      observed in gluteal adipose tissue following the intervention (P = .05); however,
      the ratio of omega-3 to omega-6 polyunsaturated fatty acids (mean ratio values of
      0.036-0.045; P = .06) was unchanged. CONCLUSION: Short-term dietary intervention
      can lead to statistically significant increases in omega-3/omega-6
      polyunsaturated fatty acid ratios in plasma and breast adipose tissue. Breast
      adipose tissue changed more rapidly than gluteal adipose tissue in response to
      the dietary modification tested in this study. Therefore, gluteal adipose tissue
      may not be a useful surrogate to study the effect of diet on breast adipose
      tissue.

PMID- 9262251
TI  - Epidemiologic aspects of gallbladder cancer: a case-control study of the SEARCH
      Program of the International Agency for Research on Cancer.
AB  - BACKGROUND: There are few previous epidemiologic studies of gallbladder cancer, a
      rare but nearly always lethal gastrointestinal cancer with a demonstrated greater
      frequency in adult women and older subjects of both sexes, and also in the
      members of populations throughout central and eastern Europe and certain racial
      groups such as native American Indians. Unfortunately, the prospects for the
      prevention of this form of cancer are poor. PURPOSE: Our purpose in conducting
      this study was to investigate possible new risk factors for gallbladder cancer
      and to strengthen our understanding of established causal agents that may be
      involved in this disease. METHODS: A large, collaborative, multicenter, case
      control study of cancer of the gallbladder was conducted in five centers located
      in Australia (Adelaide), Canada (Montreal and Toronto), The Netherlands
      (Utrecht), and Poland (Opole) from January 1983 through July 1988. Case subjects
      with gallbladder cancer were accrued by the centers from hospital pathology
      records and from reports to regional cancer registries. Cancer diagnosis was
      confirmed by either biopsy, cholecystectomy, or at the time of autopsy. Control
      subjects were randomly assigned at each center from the population. The pooled
      analysis included 196 case subjects and 1515 control subjects (who did not report
      previous cholecystectomy). Ninety-eight percent of the subjects were white.
      Personal interviews of case subjects, control subjects, and surrogates (spouse or
      next of kin) were conducted by trained personnel. RESULTS: After adjusting for
      potential confounding factors (age, sex, center, type of interview, years of
      schooling, alcohol intake, and lifetime cigarette smoking), a history of
      gallbladder symptoms requiring medical attention (e.g., reduced bile secretion
      from the gallbladder into the small intestine due to obstructions of the common
      bile or cystic ducts) was the major risk factor associated with this form of
      cancer (odds ratio [OR] = 4.4; 95% confidence interval [CI] = 2.6-7.5). This
      association was present even in subjects who had their first gallbladder
      examination because of symptoms present more than 20 years earlier (OR = 6.2; 95%
      CI = 2.8-13.4). Other variables associated with gallbladder cancer risk included
      an elevated body mass index, high total energy intake, high carbohydrate intake
      (after adjustment for total energy intake), and chronic diarrhea. All of these
      risk factors have been previously associated with gallstone disease. CONCLUSIONS:
      These findings are consistent with a major role of gallstones, or risk factors
      for gallstones, in the cause of gallbladder cancer. Additional information on
      whether or not screening high-risk subjects for gallstones or gallbladder cancer
      is needed.

PMID- 9262252
TI  - Accelerated titration designs for phase I clinical trials in oncology.
AB  - BACKGROUND: Many cancer patients in phase I clinical trials are treated at doses
      of chemotherapeutic agents that are below the biologically active level, thus
      reducing their chances for therapeutic benefit. Current phase I trials often take
      a long time to complete and provide little information about interpatient
      variability or cumulative toxicity. PURPOSE: Our objective was to develop
      alternative designs for phase I trials so that fewer patients are treated at
      subtherapeutic dose levels, trials are of reduced duration, and important
      information (i.e., cumulative toxicity and maximum tolerated dose) needed to plan
      phase II trials is obtained. METHODS: We fit a stochastic model to data from 20
      phase I trials involving the study of nine different drugs. We then simulated new
      data from the model with the parameters estimated from the actual trials and
      evaluated the performance of alternative phase I designs on this simulated data.
      Four designs were evaluated. Design 1 was a conventional design (similar to the
      commonly used modified Fibonacci method) using cohorts of three to six patients,
      with 40% dose-step increments and no intrapatient dose escalation. Designs 2
      through 4 included only one patient per cohort until one patient experienced dose
      limiting toxic effects or two patients experienced grade 2 toxic effects (during
      their first course of treatment for designs 2 and 3 or during any course of
      treatment for design 4). Designs 3 and 4 used 100% dose steps during this initial
      accelerated phase. After the initial accelerated phase, designs 2 through 4
      resorted to standard cohorts of three to six patients, with 40% dose-step
      increments. Designs 2 through 4 used intrapatient dose escalation if the worst
      toxicity is grade 0-1 in the previous course for that patient. RESULTS: Only
      three of the actual trials demonstrated cumulative toxic effects of the
      chemotherapeutic agents in patients. The average number of patients required for
      a phase I trial was reduced from 39.9 for design 1 to 24.4, 20.7, and 21.2 for
      designs 2, 3, and 4, respectively. The average number of patients who would be
      expected to have grade 0-1 toxicity as their worst toxicity over three cycles of
      treatment is 23.3 for design 1, but only 7.9, 3.9, and 4.8 for designs 2, 3, and
      4, respectively. The average number of patients with grade 3 toxicity as their
      worst toxicity increases from 5.5 for design 1 to 6.2, 6.8, and 6.2 for designs
      2, 3, and 4, respectively. The average number of patients with grade 4 toxicity
      as their worst toxicity increases from 1.9 for design 1 to 3.0, 4.3, and 3.2 for
      designs 2, 3, and 4, respectively. CONCLUSION: Accelerated titration (i.e., rapid
      intrapatient drug dose escalation) designs appear to effectively reduce the
      number of patients who are under-treated, speed the completion of phase I trials,
      and provide a substantial increase in the information obtained.

PMID- 9262253
TI  - Identical genetic changes in different histologic components of Wilms' tumors.
AB  - BACKGROUND: In young children and infants, Wilms' tumor is the most common cancer
      of the kidney. Wilms' tumor exhibits heterogeneous histopathologic features,
      consisting of rapidly proliferating blastemal and epithelial cells and a stromal
      component that has heterologous elements (e.g., cartilage, bone, and striated
      muscle). It is unclear whether the stromal and heterologous components of
      sporadic Wilms' tumor are neoplastic or should be considered non-neoplastic.
      PURPOSE: Our purpose was twofold: 1) to selectively analyze the different
      histologic tissue components of sporadic Wilms' tumors, including blastemal,
      epithelial, stromal, and heterologous elements, for loss of heterozygosity (LOH)
      of the WT1 gene and for expression of the WT1 gene and 2) to determine the role
      of WT1 gene expression in the development of these tissues. METHODS: By use of
      tissue microdissection techniques, various histologic elements (blastema, stroma,
      epithelium, and striated muscle) of sporadic Wilms' tumor were obtained from
      specimens taken from 18 patients. DNA was extracted from the dissected tissue
      fragments, and DNA solutions were amplified by use of the polymerase chain
      reaction and the polymorphic genomic markers D11S1392 and D11S904 to detect LOH
      at the WT1 gene locus (11p13). Three selected specimens with heterologous
      elements and LOH at 11p13 were analyzed for expression of the WT1 gene by means
      of the in situ reverse transcription-polymerase chain reaction. RESULTS: Nine
      (50%) of the 18 specimens showed LOH at the WT1 locus. Although identical WT1
      gene deletion was consistently observed in all of the various histologic
      components of these nine specimens, WT1 gene expression was high in the blastemal
      and epithelial elements and low in the stromal and heterologous elements.
      CONCLUSIONS AND IMPLICATIONS: Identical allelic deletion at 11p13 in all
      components of the sporadic Wilms' tumors examined suggests that the stromal
      tissue components are neoplastic rather than non-neoplastic. In conjunction with
      variable WT1 gene expression in the different histologic components, the results
      raise the possibility that undifferentiated blastemal cells are the precursors of
      the stromal and heterologous elements. Morphologically benign stromal and
      heterologous elements may therefore be derived from neoplastic cells. The
      developmental state of the various tissue components of Wilms' tumor may be
      attributed to an altered residual WT1 gene that is required for the maturation of
      blastemal and epithelial cells but that is not required for the maturation of
      stromal and heterologous elements.

PMID- 9262254
TI  - Suppression of human colorectal mucosal prostaglandins: determining the lowest
      effective aspirin dose.
AB  - BACKGROUND: A variety of studies have supported the finding that regular intake
      of aspirin (acetylsalicylic acid) or nonsteroidal anti-inflammatory agents can
      affect colorectal cancer carcinogenesis. These agents inhibit the synthesis of
      prostaglandins. High levels of prostaglandins are observed in colon cancer
      tissues. PURPOSE: Experiments were planned to determine the lowest dose of
      aspirin that can markedly suppress the levels of mucosal prostaglandins E2 and
      F(2alpha) in colorectal mucosa and to determine whether a relationship exists
      between these levels and plasma levels of both acetylsalicylic acid and its
      metabolite, salicylic acid. METHODS: Healthy men and women aged 18 years or older
      participated in the study. The participants took a single, daily dose of aspirin
      (40.5, 81, 162, 324, or 648 mg) or a placebo for 14 days. Colorectal biopsy
      specimens were taken at baseline, 24 hours after the first dose of aspirin, and
      24-30 hours and 72-78 hours after the last, i.e., fourteenth, daily dose of
      aspirin. The biopsy specimens were assayed for prostaglandins E2 and F(2alpha) by
      use of a competitive enzyme immunoassay. Plasma concentrations of acetylsalicylic
      acid and salicylic acid were determined by use of high-performance liquid
      chromatography. All P values are two-sided. RESULTS: A total of 65 subjects (10
      receiving placebo, groups of 10 each receiving 40.5, 81, 162, or 324 mg of
      aspirin, and a group of 15 receiving 648 mg of aspirin) completed the protocol.
      One subject reported unacceptable drug-induced toxic effects and did not complete
      the protocol; other subjects reported acceptable side effects. The lowest dose to
      significantly suppress colorectal mucosal prostaglandin E2 concentrations from
      baseline at 24 hours after the first dose (by 22.6%; P = .002) and at 24-30 hours
      after the last dose (by 14.2%; P = .021) was 162 mg. At 72-78 hours after the
      last dose, there was significant suppression for subjects receiving 81 mg (by
      23.7%; P = .008). The lowest dose to significantly suppress colorectal mucosal
      prostaglandin F(2alpha) concentrations from baseline at 24 hours after the first
      dose (by 18.3%; P = .032) was 324 mg. The lowest dose causing a marked reduction
      in the level of prostaglandin F(2alpha) at 24-30 hours (by 15.1%; P = .003) and
      72-78 hours (by 23.0%; P = .0002) after the last dose was 40.5 mg. No detectable
      amounts of acetylsalicylic acid or salicylic acid were present in the plasma at
      any of the biopsy time points. CONCLUSIONS: The lowest doses of aspirin taken
      daily for 14 days to significantly suppress concentrations of colorectal mucosal
      prostaglandins E2 and F(2alpha) were 81 and 40.5 mg, respectively. The
      suppression occurred without detectable amounts of aspirin or salicylic acid in
      the plasma at the time points studied. On the basis of these observations, we
      recommend a single, daily dose of 81 mg of aspirin in future studies of this drug
      as a chemopreventive agent for colorectal cancer.

PMID- 9262256
TI  - Delayed anemia and thrombocytopenia after treatment with gemcitabine.

PMID- 9262255
TI  - Cumulative prognostic value of p16/CDKN2 and p53 oncoprotein expression in
      premalignant laryngeal lesions.

PMID- 9262257
TI  - Mammography controversies: time for informed consent?

PMID- 9262258
TI  - Shall we operate on Mullerian defects? An introduction to the debate.

PMID- 9262259
TI  - Incidence of Mullerian defects in fertile and infertile women.

PMID- 9262260
TI  - Results of conventional and hysteroscopic surgery.
AB  - Mullerian anomalies usually come to medical attention when they become
      problematic and require treatment. Most of these complications require surgical
      correction. The most commonly presenting anomaly is the double uterus which can
      be the source of recurrent abortion and preterm deliveries. The Strassman, Jones
      and Tompkins metroplasties have been shown to greatly improve the rate of
      successful deliveries in these patients. Hysteroscopic metroplasty, using either
      scissors, resectoscope or laser is now the recommended treatment for most septate
      uteri due to its relative simplicity, low morbidity and excellent reproductive
      outcome.

PMID- 9262261
TI  - Endoscopic laser treatment of uterine malformations.
AB  - Hysteroscopic resection of an intrauterine septum may benefit patients suffering
      from infertility or recurrent pregnancy loss. A partial or complete uterine
      septum can be easily resected using a Nd-YAG laser. If present, the vaginal
      septum may also be removed during the same procedure. The reproductive outcome of
      women treated by operative hysteroscopy for an intrauterine septum is reviewed.
      To avoid pregnancy in a non-communicating rudimentary horn, the removal of the
      horn and the homolateral tube may be performed by either bipolar coagulation or a
      CO2 laser.

PMID- 9262262
TI  - Familial thrombophilia--the scientific rationale for thrombophylaxis in recurrent
      pregnancy loss?

PMID- 9262263
TI  - An hypothesis on the association between maternal smoking and dizygotic twinning.
AB  - There is good evidence that smoking is a marker for high steroid hormone
      concentrations (at least at the time that smoking is initiated). This would
      explain the finding that smoking is associated with dizygotic, though not
      monozygotic, twinning. The notion that smoking and other elective behaviours
      (e.g. drinking alcohol, opting for vasectomy and use of oral contraception) are
      markers or indices of high hormone concentrations may have widespread
      repercussions for cross-sectional epidemiological studies of such risk factors
      for diseases thought to be partially caused by high (e.g. prostatic and breast
      cancers) or low (e.g. rheumatoid arthritis) concentrations of these hormones.

PMID- 9262265
TI  - An artificially induced follicle stimulating hormone surge at the time of human
      chorionic gonadotrophin administration in controlled ovarian stimulation cycles
      has no effect on cumulus expansion, fertilization rate, embryo quality and
      implantation rate.
AB  - In the spontaneous menstrual cycle, the mid-cycle gonadotrophin surge causes
      maturation of the cumulus-oocyte complex, mucification of cumulus cells and
      expansion of the cumulus oophorus, resumption of meiosis and maturation of the
      cytoplasm of the oocyte. Whether this is an effect purely of luteinizing hormone
      (LH) or whether follicle stimulating hormone (FSH) also plays a role is unknown.
      The effect of an artificially induced FSH surge at the time of human chorionic
      gonadotrophin (HCG) injection on maturation of the cumulus-oocyte complex was
      investigated in a prospective randomized double-blind trial. Twelve patients
      underwent controlled ovarian hyperstimulation [long gonadotrophin-releasing
      hormone agonist (GnRHa)/human menopausal gonadotrophin (HMG) protocol] for in
      vitro fertilization (IVF) treatment. At the time of HCG administration, six
      patients received a bolus injection of FSH (450 IU i.m.); the other six patients
      received a placebo. The peak plasma concentrations of FSH of the experimental
      group were compared with the peak values of FSH obtained at the mid-cycle
      gonadotrophin surge of the natural cycle of a group of 12 volunteers to validate
      the bolus injection of FSH. Maturation of the cumulus-oocyte complex was
      quantified by measuring the expansion of the cumulus, by the fertilization rate
      and the implantation rate. The quality of the embryos was scored according the
      average morphology score. The bolus injection of FSH mimicked the mid-cycle
      gonadotrophin surge. The mean peak value of FSH (12.9 IU/l) in the experimental
      group was fully comparable with the mean peak value of FSH (10.0 IU/l) of the mid
      cycle gonadotrophin surge in the natural cycle. No effect of a bolus injection of
      FSH on the maturation of the cumulus-oocyte complex or any other outcome variable
      was found. It is not advantageous to combine the final HCG injection with a bolus
      injection of FSH in GnRHa/HMG stimulated cycles.

PMID- 9262264
TI  - Hydrosalpinges adversely affect markers of endometrial receptivity.
AB  - While in-vitro fertilization (IVF) was initially developed in women with tubal
      factor infertility, recent clinical studies have suggested that the presence of
      hydrosalpinges lowers implantation and pregnancy rates. We postulated that these
      hydrosalpinges cause impaired endometrial receptivity. A total of 103 women with
      hydrosalpinges were prospectively evaluated, and compared with 55 infertile and
      44 fertile controls. All women had endometrial biopsies during the window of
      implantation, analysed by conventional histological criteria, and also stained
      for three integrin markers of endometrial receptivity (alpha1beta1, alpha4beta1
      and alpha vbeta3). Women with hydrosalpinges (cases) expressed significantly less
      of the alpha vbeta3 integrin compared with controls. There was no difference in
      expression of alpha1beta1 or alpha4beta1 among groups. A significantly greater
      number of cases had out of phase histology and missing alpha vbeta3 (type I
      defects) and absent integrin expression despite normal histological maturation
      (type II) defects, compared with controls. Of 20 women with impaired endometrial
      receptivity who were also biopsied after hydrosalpinx surgery, 70% demonstrated
      increased alpha vbeta3 expression. Seventy-seven percent of type I and 57% of
      type II defects were corrected postoperatively. Using markers of endometrial
      receptivity, this study demonstrates that inflammatory hydrosalpinges have an
      adverse effect on endometrial receptivity, which in some cases may be overcome by
      surgical treatment of the hydrosalpinx.

PMID- 9262266
TI  - Prospective randomized study of an ultrashort gonadotrophin-releasing hormone
      agonist versus a modified suppression protocol for ovarian stimulation in
      intracytoplasmic sperm injection cycles.
AB  - To compare oocyte quality and clinical outcome after an ultrashort or a modified
      suppression gonadotrophin-releasing hormone agonist (GnRHa) protocol for ovarian
      stimulation in intracytoplasmic sperm injection (ICSI) cycles, we conducted a
      prospective randomized study of 60 consecutive couples with severe male
      infertility admitted for their first in-vitro fertilization (IVF) and ICSI
      attempt. More cycles were cancelled after the ultrashort protocol (8/30) than
      after the modified suppression protocol (3/30), although the difference was not
      significant. There were no cases of severe ovarian hyperstimulation syndrome
      (OHSS) in the ultrashort group compared to three cases in the suppression group.
      The percentage of mature metaphase II oocytes recovered in both groups was
      similar (88 versus 86%), as were the fertilization or cleavage rates after ICSI.
      In the ultrashort group, a total of 64 embryos was replaced in 22 transfers (mean
      2.9 embryos per transfer), resulting in three first trimester abortions and seven
      deliveries. In the suppression group, 11 deliveries were achieved after transfer
      of a total of 75 embryos in 27 patients (mean 2.8 embryos per transfer). In
      conclusion, there was no apparent difference between the two GnRHa protocols in
      terms of oocyte quality and clinical outcome. However, because of the lower rate
      of severe OHSS, in our study the ultrashort protocol was more appropriate for
      ovarian stimulation in ICSI cycles than the modified suppression protocol.

PMID- 9262267
TI  - Prolonged inhibition of normal ovarian cycles in the rat and cynomolgus monkeys
      following a single s.c. injection of danazol.
AB  - In castrated male rats, a single s.c. injection of danazol has been shown to
      result in an inordinately prolonged inhibition of serum luteinizing hormone (LH)
      and follicle stimulating hormone (FSH) concentrations. In the present study, we
      have examined whether the same and similar routes of administration suppresses
      ovarian function in normally cycling rats and cynomolgus monkeys. Normally
      cycling female rats received danazol as a single administration either orally,
      i.m. or s.c. and a separate group also received danazol in silastic capsules. The
      duration of the dioestrous interval until the next oestrous smear was followed
      daily and cycle lengths were compared with vehicle-treated groups. Six normally
      cycling cynomolgus monkeys were followed by daily observation and blood sampling
      at 2-3 day intervals. After one normal cycle, danazol (200 mg/kg) was
      administered as a single s.c. injection. Monkeys were followed until the next
      menses and one cycle thereafter and blood samples were assayed for oestradiol,
      progesterone and bioactive LH. Oestrous cycle length in vehicle-treated control
      rats was 4.7 days. A single administration of danazol s.c. at the higher dose
      prolonged the dioestrous interval to 31.3 days (P <0.001) and a similar
      prolongation was observed with this high dose when administered i.m. (27.7 days;
      P <0.001). In normally cycling monkeys, the menstrual cycle length was 30.2 days,
      but following a single danazol administration, the mean duration to the next
      menses was prolonged to 117.5 days (P <0.001). In five out of six monkeys, there
      was a decrease in LH and an absence of normal oestradiol and progesterone
      patterns. After this prolonged hiatus, a subsequent menstrual cycle was normal in
      length and endocrine pattern. A single s.c. administration of danazol resulted in
      a prolonged suppression of ovarian cyclicity in both normally cycling rats and
      cynomolgus monkeys.

PMID- 9262268
TI  - A pilot study of the human chorionic gonadotrophin test for ovarian
      hyperandrogenism.
AB  - A controlled clinical study was designed to investigate the value of human
      chorionic gonadotrophin (HCG) challenge as a test for functional ovarian
      hyperandrogenism. Dexamethasone administration was followed by 5000 IU HCG and
      blood samples for steroid hormone assay were obtained 0, 8, 16, and 24 h
      thereafter. Study subjects were normal women (n = 13); women with functional
      ovarian hyperandrogenism, defined by androgen excess, amenorrhoea and an
      increased 17-hydroxyprogesterone response to nafarelin (n = 6); and normal men (n
      = 4). The responses of 17-hydroxyprogesterone, androstenedione and testosterone
      to HCG in women with functional ovarian hyperandrogenism were significantly
      greater than in normal women. However, the 17-hydroxyprogesterone response to HCG
      in functional ovarian hyperandrogenism was significantly lower after HCG than
      after nafarelin. The oestradiol response was also significantly lower after HCG
      than nafarelin, although oestradiol concentration more than doubled in normal
      women as well as in women with functional ovarian hyperandrogenism. The responses
      to HCG confirm that functional ovarian hyperandrogenism abnormalities are
      luteinizing hormone (LH)-dependent. Therefore, the 17-hydroxyprogesterone
      response to HCG could represent a useful test for the diagnosis of ovarian
      hyperandrogenism. The lower 17-hydroxyprogesterone response to HCG than to
      nafarelin in functional ovarian hyperandrogenism suggests that a follicle
      stimulating hormone (FSH)-responsive factor modulates thecal 17
      hydroxyprogesterone secretion. The oestradiol response to HCG is consistent with
      HCG directly stimulating the oestradiol secretion by thecal cells.

PMID- 9262269
TI  - Post-suckling prolactin:oestradiol ratio--a potential index to predict the
      duration of lactational amenorrhoea in women.
AB  - To assess whether the duration of lactational amenorrhoea can be predicted in
      individual women, we studied the pre- and post-suckling concentrations of immune
      prolactin (IR-PRL) and of bioactive prolactin (BIO-PRL) and basal concentrations
      of oestradiol in ten amenorrhoeic fully nursing women at 3 months post-partum.
      The women were of similar age, weight and had infants of similar growth rate.
      Five of these women were to experience long amenorrhoea (>180 days) and the
      others short amenorrhoea (<180 days). Blood samples were drawn 30 min after a
      suckling episode initiated at 0800 h, 1600 h and 2400 h. BIO-PRL distinguished
      between groups of women at 0030 h but not at other times, while there was
      considerable overlap between values for IR-PRL and oestradiol at all times
      studied. At 1630 h, the ratios post-suckling BIO-PRL: oestradiol and post
      suckling IR-PRL:oestradiol were above 2000 in the women that were to experience
      long amenorrhoea and below this threshold in the other women. The ratio post
      suckling BIO-PRL:oestradiol provided more information since the difference
      between the lowest ratio in the long amenorrhoea and the highest ratio in the
      short was 699, while it was 520 for the IR-PRL:oestradiol ratio. The
      determination of these ratios may help to predict the duration of lactational
      amenorrhoea in individual fully nursing women.

PMID- 9262270
TI  - A randomized study on the effects of intramuscular injections with urinary
      gonadotrophins (Humegon or Pergonal) on pain, local redness and fever in
      infertile women opting for in-vitro fertilization.
AB  - The objective of this open, multicentre, randomized controlled study in women
      opting for in-vitro fertilization was to compare the occurrence of pain and
      redness at the injection site and of post-injection fever after i.m. injection
      with Humegon (n = 89) or Pergonal (n = 92). Assessments were scoring of pain and
      redness at the injection site and of post-injection fever during the next 24 h
      using self-administered questionnaires. Injection site pain was reported in 48.9%
      of injections with Humegon and in 44.9% with Pergonal (P = 0.45). A trend was
      seen towards more redness after Pergonal injection (24.0 versus 15.5%; P = 0.08).
      Post-injection fever was reported in 1.4% with Humegon and in 1.1% with Pergonal
      (P = 0.80). It was concluded that there are no statistically significant
      differences between Humegon and Pergonal after i.m. injection with respect to the
      prevalence of pain and redness at the injection site and of post-injection fever.

PMID- 9262271
TI  - Oestrogen receptor gene polymorphisms and ovarian stimulation for in-vitro
      fertilization.
AB  - Experimental evidence has shown that mice lacking the oestrogen receptor (ESR)
      gene are infertile with cystic ovaries and follicular arrest. In humans, several
      polymorphisms and mutations in the ESR gene have been identified. In this study
      we have analysed a common PvuII and a rare BstUI polymorphism in the ESR gene.
      Analysis was carried out on DNA samples from women undergoing ovarian stimulation
      for in-vitro fertilization (IVF) and embryo transfer and controls having at least
      one pregnancy. Comparisons were done between the three PvuII genotypes,
      concerning the mean numbers of follicles and oocytes and the mean ratios of
      follicles to oocytes harvested in two consecutive cycles. Significantly lower
      ratios were identified in the group lacking the PvuII polymorphism, compared with
      the groups with heterozygous or homozygous PvuII polymorphisms (P > 0.05 and P >
      0.01 respectively). The rare haplotype having both PvuII and BstUI restriction
      sites on one chromosome was present only in the IVF group. Pregnancies from IVF
      were significantly rarer in patients who were homozygous for the PvuII
      polymorphism (P > 0.05). Our results suggest that genetic variability in the ESR
      has a role in the quality of the ovarian follicles as judged by the ovarian
      response to stimulation and may also affect implantation.

PMID- 9262273
TI  - Is routine diagnostic laparoscopy for infertility still justified? A pilot study
      assessing the use of hysterosalpingo-contrast sonography and magnetic resonance
      imaging.
AB  - We assessed the value of hysterosalpingo-contrast sonography (HyCoSy) and
      magnetic resonance imaging (MRI) as alternatives to laparoscopy and dye
      insufflation with or without hysteroscopy in the investigation of infertility. A
      total of 19 women had all three procedures, in addition, one became pregnant
      after HyCoSy alone. The findings were: uterine fibroids (n = 5), minimal-mild
      endometriosis (n = 4) and moderate-severe endometriosis (n = 3) including one
      case of bilateral endometriomas, endometrial polyp (n = 1), polycystic ovaries (n
      = 2), bilateral dermoid cysts (n = 1), haemorrhagic corpus luteal cyst (n = 1)
      and minimal adhesions (n = 3). At laparoscopy, 31/37 tubes were patent and there
      was 84% concordance with the tubal patency findings at HyCoSy. The uterine
      fibroids and ovarian cysts were detected using transvaginal scanning; the
      endometrial polyp and a congenital uterine anomaly were identified using HyCoSy.
      These findings were detected using MRI, but in addition the technique
      distinguished the dermoid cysts from the endometriomas, identified the two other
      cases of moderate-severe endometriosis, fibroids <2 cm (n = 2) and adenomyosis (n
      = 5), and interpreted the haemorrhagic corpus luteum as an endometrioma. Our data
      suggest that women with normal HyCoSy and MRI findings have a normal pelvis and
      may not need routine surgical investigation.

PMID- 9262274
TI  - How effective is patient-controlled analgesia? A randomized comparison of two
      protocols for pain relief during oocyte recovery.
AB  - Although the conventional method of pain relief during outpatient oocyte recovery
      involves physician-administered drugs, patient-controlled analgesia (PCA) offers
      an alternative technique with the potential to give women more control over
      peroperative analgesia. We conducted a prospective randomized study to compare
      the effect of fentanyl administered either through a PCA delivery system or by a
      physician. Thirty-nine women were randomized to PCA during egg collection while
      42 were allocated to receive intermittent doses administered by a physician. Pain
      was evaluated by means of a 100 mm linear analogue scale. The mean (SD) pain
      score in the PCA group was 38.5 (19.8) while in the other group it was 46.1
      (21.3) (P = 0.1). In the PCA group, 64% of women felt very satisfied with their
      analgesia as compared with 57% in the non-PCA group (P = 0.6). Among the PCA
      users, 39% of demands were successful. Significantly more fentanyl (97.5 microg)
      was used in the PCA group than in the other group (84.6 microg) (P = 0.03).
      Though intraoperative PCA with fentanyl is an effective alternative to physician
      administered techniques, many women still feel the need for more analgesia during
      the procedure.

PMID- 9262272
TI  - Two successful pregnancies in a 46,XY patient.
AB  - Two successful pregnancies (singleton followed by twins) following ovum
      donation/in-vitro fertilization in a 46,XY woman have been studied. Although
      similar cases have previously been presented: in a pure XY patient and in a
      45,X/46,XY patient, this case is one in which a subsequent successful pregnancy
      has resulted. In such patients, the rate of Caesarean section appears to be
      increased, and we postulate that the hypoplastic nature of the uterus, although
      able to respond quite well to both exogenous and endogenous hormones to accept
      and maintain a pregnancy, may lack the capability to respond fully in labour by
      dilating appropriately.

PMID- 9262275
TI  - The use of laparoscopic ovarian electrocautery in preventing cancellation of in
      vitro fertilization treatment cycles due to risk of ovarian hyperstimulation
      syndrome in women with polycystic ovaries.
AB  - Fifty women with polycystic ovaries took part in a prospective randomized study.
      All women required treatment by in-vitro fertilization (IVF) for reasons other
      than anovulation. They had all previously undergone ovarian stimulation with
      gonadotrophin therapy which had failed to result in pregnancy or had been
      abandoned due to high risk of developing ovarian hyperstimulation syndrome
      (OHSS). Twenty-five women were treated by long-term pituitary desensitization
      followed by gonadotrophin therapy, oocyte retrieval and embryo transfer (group
      1). Twenty-five women underwent laparoscopic ovarian electrocautery after
      pituitary desensitization followed by gonadotrophin therapy, oocyte retrieval and
      embryo transfer (group 2). A significantly higher number of women in group 1 had
      to have the treatment cycle abandoned due to impending or actual OHSS, determined
      by endocrine and clinical findings. In addition, the development of moderate or
      severe OHSS in completed cycles was higher in group 1. The pregnancy rate and
      miscarriage rates in the two treatment groups were similar. The authors propose
      that laparoscopic ovarian electrocautery is a potentially useful treatment for
      women who have previously had an IVF treatment cycle cancelled due to risk of
      OHSS or who have suffered OHSS in a previous treatment cycle.

PMID- 9262276
TI  - Repeating episodes of low fecundability. A multicentre European study. The
      European Study Group on Infertility and Subfecundity.
AB  - Many reproductive failures tend to repeat themselves within the same couple.
      Whether fecundability (the probability of conceiving in a given number of
      menstrual cycles) follows the same pattern is studied using data from the
      European Studies on Infertility and Subfecundity (ESIS): 6630 women were
      interviewed on 'time to pregnancy' (TTP) and other aspects of their pregnancy
      history. Surveys were conducted between 1991 and 1994 in seven regions from five
      European countries. Furthermore, the pattern of fecundability in this population
      was compared with results from computer simulations based upon a population with
      fixed fecundability parameters. Results from ESIS speak in favour of the
      stability of fecundability in the relatively short reproductive life of a couple.
      However, a substantial proportion of couples with up to two events of
      subfecundability (TTP >9.5 months) became pregnant shortly after trying again.
      This finding calls for reservation in starting expensive and/ or unpleasant
      diagnostic procedures at an early stage when a couple tries to become pregnant
      again.

PMID- 9262277
TI  - The application of neural networks in predicting the outcome of in-vitro
      fertilization.
AB  - Infertility affects one in six couples at some time in their lives, with 48% of
      these couples requiring assisted conception techniques in order to achieve a
      pregnancy. Whilst the overall clinical pregnancy rate per embryo transfer is 23%,
      this varies widely between clinics. The Human Fertilisation and Embryology
      Authority has attempted to analyse the results of all units, with weighting of
      different factors affecting assisted conception, and the published data have
      invariably led to comparisons between units. However, statistical models need to
      be developed to eliminate bias for valid comparisons. Neural networks offer a
      novel approach to pattern recognition. In some instances neural networks can
      identify a wider range of associations than other statistical techniques due in
      part to their ability to recognize highly non-linear associations. It was hoped
      that a neural network approach may be able to predict success for individual
      couples about to undergo in-vitro fertilization (IVF) treatment. A neural network
      was constructed using the variables of age, number of eggs recovered, number of
      embryos transferred and whether there was embryo freezing. Overall the network
      managed to achieve an accuracy of 59%.

PMID- 9262278
TI  - Intrauterine insemination after ovarian stimulation with clomiphene citrate:
      predictive potential of inseminating motile count and sperm morphology.
AB  - This retrospective study aimed to evaluate the prognostic value of the
      inseminating motile count (IMC) and sperm morphology (using strict criteria) on
      success rates after homologous intrauterine insemination (IUI) combined with
      clomiphene citrate (CC) stimulation. A total of 373 couples underwent 792 IUI
      cycles in a predominantly (87.4%) male subfertility group. The overall cycle
      fecundity (CF) and baby take-home rate (BTH) was 14.6 and 9.9% respectively. The
      cumulative CF and BTH (per couple) after three cycles were 30.6 and 21.1%
      respectively. Overall, sperm morphology and IMC were of no prognostic value using
      receiver operating characteristic (ROC) curve analysis, but after classifying the
      study population into different subgroups according to IMC, sperm morphology
      turned out to be a valuable prognostic parameter in subgroup 1, i.e. IMC <1 x
      10(6). In this subgroup, no pregnancies were seen when the morphology score was
      <4% and the mean value of sperm morphology was significantly different in the
      pregnant (8.3%) versus non-pregnant group (5.0%; P <0.05). The cumulative CF and
      BTH after three IUI cycles were comparable for all couples with the exception of
      those cases in which the IMC was <1 x 10(6) with a morphology score of <4% normal
      forms. We recorded only two twin pregnancies (2.5%) and no moderate or severe
      ovarian hyperstimulation syndrome. We conclude that in a selected group of
      patients without CC resistance and normal ovarian response following CC
      stimulation [maximum of three follicles with a diameter of >16 mm at the time of
      administration of human chorionic gonadotrophin (HCG)], IUI combined with CC-HCG
      can be offered as a very safe and non-expensive first-line treatment, at least
      with an IMC of >1 x 10(6) spermatozoa. In cases with <1 x 10(6) spermatozoa, CC
      IUI remains important as a first-choice therapy provided the morphology score is
      > or =4%.

PMID- 9262279
TI  - Chlamydial serology in 1303 asymptomatic subfertile couples.
AB  - The clinical significance of antichlamydial antibodies (Chlam Ab) was determined
      in a total of 1303 subfertile couples consulting for infertility investigation
      and treatment. Median age of the women was 30 (range 22-44) years and of the men
      33 (range 21-53) years. The median duration of infertility was 4 (range 1-21)
      years. All patients were asymptomatic for genital tract infection. A
      comprehensive infertility investigation included examination of the endocrine,
      cervical, and tubal factor, and semen analysis, antisperm antibody (ASA) testing,
      sperm-mucus interaction testing in vitro using a standardized protocol, and post
      coital testing (PCT). Screening for Chlam IgG Ab was performed in serum of both
      partners, obtained at the same time. Simultaneous microbial cultures in genital
      secretions of both partners included a broad spectrum of potentially pathogenic
      bacteria. Elevated titres of Chlam IgG Ab as seromarker for previous infection
      were found in 20.8% of all women, and in 12.6% of men. Chlam Ab were
      significantly more frequent in partners of seropositive patients (in 51.8% of
      women with a Chlam Ab positive partner, compared to 15.8% of the other women).
      Microbial screening outcome was not significantly related to results of
      chlamydial serology in both partners. In women, elevated titres of Chlam Ab were
      significantly associated with a tubal factor, but were not related to reduced
      quality of the endocervical mucus (CM), including the in-vitro penetrability of
      the CM (using partners' or donors' spermatozoa). In males, Chlam Ab were not
      significantly related to the outcome of semen analysis, including screening for
      ASA (IgG and/or IgA) in semen, and several parameters of sperm functional
      capacity. After exclusion of couples with tubal disease, subsequent male
      fertility did not significantly differ in males with or without Chlam Ab. The
      results suggest that during basic infertility investigation, positive chlamydial
      serology as an easy screening procedure indicates a higher risk for a tubal
      infertility factor. However, in asymptomatic patients, Chlam IgG Ab in serum are
      not associated with a cervical factor or with the male factor, using several
      determinants for evaluation of semen quality including subsequent fertilizing
      capacity.

PMID- 9262280
TI  - Seminal cytokine concentrations (IL-1beta, IL-2, IL-6, sR IL-2, sR IL-6), semen
      parameters and blood hormonal status in male infertility.
AB  - Several lines of evidence indicate that cyokines are involved in male fertility.
      They are secreted by different parts of the male genital tract and may exert
      effects on steroidogenesis, spermatogenesis and sperm functions. We measured the
      concentrations of interleukins (IL-beta, IL-2, IL-6) and those of interleukin
      soluble receptors (sR IL-2, SR IL-6) in semen of fertile subjects (n = 21) and of
      patients with a range of andrological diseases (n = 119). The seminal
      concentrations of cytokines were analysed according to semen parameters as well
      as to the blood hormonal profiles of follicle stimulating hormone, luteinizing
      hormone and testosterone. An increase of IL-1beta was observed in the group of
      patients with infertility. No difference was found between the different
      subgroups defined on the basis of progressive motility, percentage of abnormal
      forms and diagnosis of infection. The seminal cytokine concentrations were
      independent of the blood hormonal status. Our data suggest that the determination
      of interleukins (-1beta, -2 and -6) or interleukin soluble receptors (sR IL-2, sR
      IL-6) in human spermatozoa does not provide convenient information in male
      routine infertility work-up.

PMID- 9262281
TI  - A challenge to the concept that the use of calcium channel blockers causes
      reversible male infertility.
AB  - The objective of this study was retrospectively to evaluate both in-vitro
      fertilization (IVF) and non-IVF cycles in which the male partner had been taking
      calcium channel blockers, either to confirm or refute previous data from another
      centre, suggesting that these drugs cause a severe but reversible subfertility
      problem in the male. These drugs were found to inhibit expression of mannose
      ligand binding receptors, thus preventing spermatozoa from attaching to the zona
      pellucida; they were postulated to cause failed fertilization based on one case
      having this defect, in whom a return to normal was achieved after stopping the
      drug. However, the couple did not undergo a cycle with IVF to see if
      fertilization now occurred. The data presented here demonstrated fertilization in
      all patients having IVF who were taking calcium channel blockers. The subsequent
      pregnancy rate per transfer was 17.4%. Also, five out of 11 (45.4%) non-IVF
      patients conceived after correction of various female factors. Failure of the
      other six patients to conceive could be explained by other confounding factors,
      especially oligoasthenozoospermia. Taking into consideration other data
      suggesting poor fertilization when this mannose-ligand binding receptor
      abnormality was demonstrated, we propose the possibility that this defect, when
      not associated with calcium channel blockers, may be associated with some other
      cryptic factor that causes poor fertilization. According to our hypothesis,
      calcium channel blockers might cause the problem in mannose expression but also
      adversely affect some other factor that is deficient when non-drug related
      abnormalities in mannose-ligand binding expression are found.

PMID- 9262282
TI  - Testicular needle aspiration as an alternative to biopsy for the assessment of
      spermatogenesis.
AB  - The technique of fine needle aspiration (FNA) may have a role as a reliable,
      quick and easy method of obtaining testicular tissue. Recent advances in the
      management of male subfertility and, in particular, the finding that spermatozoa
      recovered from the epididymis and testis can result in embryo generation after
      intracytoplasmic sperm injection (ICSI), question the traditional role of open
      testicular biopsy for the assessment of spermatogenesis. FNA of the testis was
      performed on 19 cases of male subfertility and histological and cytological
      preparations obtained were assessed by light microscopy. FNA provided intact
      testicular tubules adequate for the histological assessment of spermatogenesis in
      all cases. There was good correlation with the cytological preparations which
      gave an indication of the number of mature spermatozoa present. FNA should be
      considered as a simple alternative to open testicular biopsy in the current
      investigation of male subfertility and as a method of retrieving spermatozoa for
      assisted conception using ICSI.

PMID- 9262283
TI  - Testicular sperm retrieval by percutaneous fine needle sperm aspiration compared
      with testicular sperm extraction by open biopsy in men with non-obstructive
      azoospermia.
AB  - The efficiency of testicular sperm retrieval by testicular fine needle aspiration
      (TEFNA) was compared with open biopsy and testicular sperm extraction (TESE), in
      37 rigorously selected patients with non-obstructive azoospermia. All patients
      underwent TEFNA and TESE consecutively. Thus, each patient served as his own
      control. The case was regarded as successful if at least one testicular
      spermatozoon was found allowing intracytoplasmic sperm injection (ICSI) of at
      least one oocyte. The mean age of the male patients was 32.7 years (range 24-47).
      Whereas by TEFNA spermatozoa enabling performance of ICSI were found in only four
      patients out of 37 (11%), open biopsy and TESE yielded spermatozoa in 16 cases
      (43%). The negative predictive value of high serum follicle stimulating hormone
      (FSH) concentrations (> or =10 IU/l) (predicting failure to find spermatozoa for
      ICSI) was low (38.4%). The positive predictive value (predicting the chance to
      find spermatozoa for ICSI) of normal-sized testicle was not different from that
      of small-sized (<15 ml) testicle (50%). Complications included one case of
      testicular bleeding following fine needle aspiration, treated locally, and two
      cases of extratunical haematomata following TESE requiring no intervention. In
      patients with non-obstructive azoospermia, TEFNA has a significantly lower yield
      compared to TESE. Performance of ICSI with testicular sperm in these cases
      resulted in satisfactory fertilization and high embryo transfer rates. The
      implantation and pregnancy rates per embryo transfer were 13 and 29%
      respectively. Neither serum FSH values nor testicular size were predictive of the
      chances to find spermatozoa for ICSI. Some complications may occur even following
      TEFNA.

PMID- 9262284
TI  - Single versus double insemination: a retrospective audit of pregnancy rates with
      two treatment protocols in donor insemination.
AB  - Our objective was to evaluate the effect of a change in treatment protocols,
      suggested following an inspection visit by the regulatory authority, from single
      to double inseminations during donor insemination treatment cycles. We therefore
      conducted a retrospective audit of pregnancy rates in the reproductive medicine
      clinic of a major teaching hospital. All patients were treated for male factor
      infertility by donor insemination, without ovulation induction with
      gonadotrophins between October 1992 and December 1995. The main outcome measures
      were cumulative conception and live birth rates. During the study period 250
      patients underwent treatment and 650 single insemination and 277 double
      insemination treatment cycles were undertaken. The pregnancy rate per cycle was
      0.054 and 0.119 for single and double insemination respectively. After six cycles
      the cumulative pregnancy rates were 0.28 and 0.47 and the take-home baby rates
      were 0.25 and 0.37 for single and double inseminations respectively. The change
      in practice from single to double insemination resulted in a doubling of the
      pregnancy rate per treatment cycle. Cumulative pregnancy rates after two
      treatment cycles of double insemination were comparable with those achieved after
      six cycles of single insemination. These results have significant implications
      for both patients and purchasers.

PMID- 9262285
TI  - Successful intracytoplasmic sperm injection with spermatozoa from a patient with
      dysplasia of the fibrous sheath and chronic respiratory disease.
AB  - The present report describes a successful intracytoplasmic sperm injection (ICSI)
      procedure performed with immotile spermatozoa from a young man with a combination
      of dysplasia of the fibrous sheath and dynein deficiency, a recently described
      variant of the immotile cilia syndrome. This methodology provides the only
      suitable solution for these patients in whom all other assisted fertilization
      technologies have previously failed, and opens the possibilities for treatment of
      male infertility due to severe, irreversible sperm defects such as the one
      reported here.

PMID- 9262286
TI  - Placental protein 14 production by human Fallopian tube epithelial cells in
      vitro.
AB  - We studied the in-vitro secretory function of non-polarized and polarized
      cultured Fallopian tube epithelial cells by measurement of the placental protein
      14 (PP14) secretion in primary cultures and subcultures from Fallopian tubes
      obtained from eight premenopausal women in different phases of the ovarian cycle.
      Primary cultures were established in minimal essential medium in Earle's salts
      supplemented with fetal bovine serum and the cells were subcultured for six
      passages, in the polarized cell cultures, the cells being seeded on an
      extracellular matrix system. Cell freezing was carried out using 10% dimethyl
      sulphoxide. PP14 secretion into the culture media was measured by a
      radioimmunoassay using 125I-PP14 as label and rabbit anti-human PP14 serum. There
      was a large amount of PP14 secretion into the culture media in primary cultures,
      the secretion decreasing considerably after subculture 1. PP14 secretion after
      subculture 2 was not different from the control values. Polarized and non
      polarized cells secreted similar amounts of PP14 and frozen-thawed cells did not
      appear to secrete PP14. Epithelial cells from Fallopian tubes obtained at
      different phases of the ovarian cycle did not appear to show any difference in
      PP14 secretion rates. Our data suggest that the in-vitro secretion of PP14 by
      human Fallopian tube epithelial cells is adversely affected by cell ageing and
      freezing.

PMID- 9262287
TI  - Macrophages in normal cycling human ovaries; immunohistochemical localization and
      characterization.
AB  - We evaluated the immunolocalization and characterization of macrophages in 28
      normal cycling human ovaries. Two primary antibodies were used to detect the
      macrophages: PGM1, a general marker for macrophages, and 25F9 which is specific
      for phagocytosing macrophages. Spindle-shaped cells positive for PGM1 but
      negative for 25F9 were observed in the stroma (123.6 +/- 1.05 cells/10(-6) m2)
      and theca layer of the follicle (mean ranged from 22.61 to 53.79) and the number
      of these cells did not change throughout the cycle. After ovulation, PGM1
      positive cells with ballooning bodies began to appear in the early corpus luteum
      (111.8 +/- 0.83). The number of these macrophages increased in the mid and late
      corpora lutea, and reached maximum in the early degenerating corpus luteum
      (1231.0 +/- 3.29). A lower number of PGM1 positive ballooning macrophages were
      observed in the atretic follicle (177.9 +/- 1.42). 25F9 positive cells were also
      observed among the PGM1 positive balloon-shaped cells. The number of cells double
      positive for 25F9 and PGM1 was observed in the mid corpus luteum (44.6 +/- 0.46),
      increased in the late corpus luteum and early degenerating corpus luteum, and
      reached plateau in the late degenerating corpus luteum (549.0 +/- 5.82). A lower
      number of these double positive macrophages were also observed in the atretic
      follicle (64.8 +/- 0.36). The ratio of 25F9 to PGM1 positive cells increased in
      parallel with ageing of the corpus luteum (0.19 in the mid corpus luteum, 0.39 in
      the late corpus luteum, and 0.37 in the early degenerating corpus luteum), and
      the great majority of PGM1 positive cells were also immunopositive for 25F9 in
      the late degenerating corpus luteum (0.81). These results suggest that in normal
      cycling human ovaries, macrophages are mainly involved in luteal regression as
      scavengers.

PMID- 9262288
TI  - Selective transfer of cryopreserved human embryos with further cleavage after
      thawing increases delivery and implantation rates.
AB  - We investigated whether further in-vitro culture of human multicellular embryos
      that survive cryopreservation can select the viable embryos for transfer. Embryos
      for cryopreservation were supernumerary multicellular embryos obtained after in
      vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatments,
      with <20% of their volume filled with anucleate fragments. These had been
      cryopreserved using a slow-freezing and slow-thawing protocol with 1.5 M
      dimethylsulphoxide as the cryoprotectant. From the start of our cryopreservation
      programme until September 12, 1994, the thawing strategy was to thaw frozen
      embryos up to the exact number needed for transfer. Embryos for transfer were
      selected on the basis of their morphological appearance and embryo transfer to
      the patient was done on the day of thawing. From September 12, 1994 onwards we
      used a more selective thawing strategy where a cohort of up to a maximum of 12
      frozen embryos per patient is thawed from which embryos of the best morphological
      quality, and which are furthest advanced in terms of cleavage after a 24 h in
      vitro culture period in Menezo B2 medium, are selected. We took delivery rates,
      embryo implantation rates and birth rates into account to see if there is any
      difference between the following three types of transfers used: 187 transfers
      exclusively of embryos having continued to cleave after thawing, 107 mixed
      transfers of embryos with and without further cleavage and 53 transfers
      exclusively of embryos with no further cleavage. The overall outcome in terms of
      delivery rate and embryo implantation and birth rates were not different between
      the new and the earlier thawing policies (6.6, 5.2 and 3.6% versus 6.0, 4.1 and
      2.7% respectively). Only when a distinction was made between transfers on the
      basis of the presence of embryos with further cleavage, did the advantage of
      selection on the basis of cleavage capacity become evident. Significantly higher
      delivery and embryo implantation and birth rates (11.2, 7.7 and 6.5%
      respectively) were recorded with transfers exclusively of embryos with further
      cleavage versus mixed transfers of embryos with and without further cleavage
      (1.9, 2.9 and 0.6% respectively). Fifty-three transfers exclusively of embryos
      with no further cleavage did not lead to any delivery. Our results demonstrate
      that selection of human multicellular embryos which survive cryopreservation and
      continue to cleave in vitro can significantly improve the delivery rate per
      transfer and the implantation rate per transferred embryo.

PMID- 9262289
TI  - Cryopreservation: the practicalities of evaluation.
AB  - An attempt was made to integrate data from cryopreserved embryos with those from
      fresh embryos to obtain a realistic assessment of the role of cryopreservation in
      assisted reproductive treatment. Principles were applied to previously published
      data from a large prospective randomized multicentre study comprising recombinant
      and urinary follicle stimulating hormone in in-vitro fertilization.

PMID- 9262290
TI  - Reduced pregnancy rates following the transfer of human embryos frozen or thawed
      in culture media supplemented with normal serum albumin.
AB  - Over a 26 month period 17% of couples having treatment in our clinical programmes
      selected a commercially available protein (normal serum albumin, NSA) prepared
      from pooled human sera instead of using their own serum as a supplement for their
      embryo culture media. In a retrospective analysis of >2000 gonadotrophin
      stimulated cycles and 1000 cycles where frozen/thawed embryos were transferred,
      fertilization, embryo quality and pregnancy rates following in-vitro
      fertilization (IVF), gamete intra-Fallopian transfer (GIFT) or intracytoplasmic
      sperm injection (ICSI) were unaffected by the type of protein used to supplement
      the culture medium. When embryos were thawed in medium containing NSA, both
      pregnancy (PR) and implantation rates (IR) were significantly lower (P <0.05)
      than if the medium was supplemented with serum (PR 8.3% and 17.5%; IR 4.6% and
      10.5%). Inclusion of NSA before freezing reduced the IR of thawed embryos. To
      further test this observation all cycles where embryos were cultured and frozen
      in medium containing NSA (173 cycles) were matched to cycles where serum was used
      and the outcome was compared. At the end of 1995 just over half of the embryos in
      both groups had been thawed. No statistical difference was noted in the pregnancy
      rates (NSA, 5.6% versus serum, 11.3%) but the IR per embryo was significantly
      lower when embryos were cultured and frozen in medium supplemented with NSA
      (2.2%) than when serum was used as the supplement (6.6%).

PMID- 9262291
TI  - Early cleavage of in-vitro fertilized human embryos to the 2-cell stage: a novel
      indicator of embryo quality and viability.
AB  - A number of non-invasive methods have been proposed to evaluate embryo viability
      in human in-vitro fertilization programmes. In addition to biochemical analyses,
      a common method for the selection of embryos prior to transfer involves
      assessment of embryo quality and morphology. We propose a new method to evaluate
      embryo viability based on the timing of the first cell division. Fertilized
      embryos that had cleaved to the 2-cell stage 25 h post-insemination were
      designated as 'early cleavage' embryos while the others that had not yet reached
      the 2-cell stage were designated as 'no early cleavage'. In all cases the early
      cleavage embryos were transferred when available. Early cleavage was observed in
      27 (18.9%) of the 143 cycles assessed. There were significantly (chi2 = 4.0; P =
      0.04) more clinical pregnancies in the early cleavage group, 9/27 (33.3%),
      compared with the no early cleavage group, 17/116 (14.7%). No difference was
      found when comparing key parameters (age, stimulation protocol and semen
      characteristics) of couples belonging to both groups, pointing to an intrinsic
      property or factor(s) within the early cleaving embryos. We propose 'early
      cleavage' as a simple and effective non-invasive method for selection and
      evaluation of embryos prior to transfer.

PMID- 9262292
TI  - Use of reverse transcription-polymerase chain reaction to detect embryonic
      interleukin-1 system messenger RNA in individual preimplantation mouse embryos co
      cultured with Vero cells.
AB  - In this study, we report a total of 292 mouse embryos cultured on Vero cell
      monolayers and 77 embryos cultured in medium alone at different preimplantation
      stages examined individually for embryonic mRNA of beta-actin, interleukin-1beta
      (IL-1beta), interleukin-1 receptor antagonist (icIL-1ra) and interleukin-1
      receptor type I (IL-1RtI) using reverse transcription and two-step polymerase
      chain reaction (RT-PCR). The rates of blastocyst formation and blastocyst
      hatching were both significantly higher in embryos co-cultured with Vero cells in
      comparison with the embryos cultured in control medium (81.2 +/- 2.6 versus 42.2
      +/- 3.7%, P < 0.001; 75.6 +/- 2.7 versus 19.2 +/- 6.2%, P < 0.001 respectively).
      We have identified a similar pattern of interleukin-1 family embryonic mRNA
      transcripts expressed from the compact morula stage through to hatching
      blastocyst in both control and Vero cell cultured embryos with significantly
      increased icIL-1ra transcript at hatching blastocyst stage (P < 0.05, P < 0.001
      respectively). There was a significant increase in IL-1beta mRNA transcripts of
      embryos at hatching blastocyst stage compared to compact morula stage in Vero
      cell cultured embryos (P < 0.05). These findings support the hypothesis that the
      IL-1 system is an important factor in embryo-maternal molecular communication
      during the implantation process.

PMID- 9262293
TI  - Embryo morphology or cleavage stage: how to select the best embryos for transfer
      after in-vitro fertilization.
AB  - This retrospective study of 1001 in-vitro fertilization (IVF) cycles included a
      consecutive series of single transfers (n = 341), dual transfers (n = 410) and
      triple transfers (n = 250) where all the transferred embryos in each cycle were
      of identical quality score and identical cleavage stage. In our 2 day culture
      system, transfer of 4-cell embryos resulted in a significantly higher
      implantation rate and pregnancy rate (23 and 49%) compared with 2-cell embryos
      (12 and 22%) and 3-cell embryos (7 and 15%). Furthermore, the transfer of 4-cell
      embryos resulted in a significantly higher pregnancy rate compared with embryos
      that had cleaved beyond the 4-cell stage (28%). The implantation rate (21%) and
      pregnancy rate (43%) after transfer of embryos of score 1.0 were significantly
      higher than after transfer of embryos of score 2.0 (14 and 32% respectively).
      Transferring embryos of score 2.1 resulted in significantly higher implantation
      rates (26%) and similar pregnancy rates compared with score 1.0. Transferring
      embryos of score 2.2-3.0 resulted in a significantly lower implantation rate (5%)
      and pregnancy rate (15%). A striking finding was that embryos of quality score
      2.0 had a significantly lower implantation rate compared with embryos of quality
      score 1.0 and 2.1 and a significantly lower pregnancy rate compared to embryos of
      quality score 1.0. We also found a lower implantation rate and pregnancy rate
      when transferring 3-cell embryos. These findings may indicate periods of
      increased sensitivity to damage during the cell cycle. In conclusion, these
      results substantiate the idea of the superiority of 4-cell embryos and
      demonstrate that minor amounts of fragments in the embryo may not be of any
      importance. These findings may call for a shift when weighing the two main
      morphological components (quality score and cleavage stage) in the sense that
      reaching a 4-cell cleavage stage even with the presence of a minor amount of
      fragments should be preferred to a 2-cell embryo with no fragments.

PMID- 9262294
TI  - Cryopreservation of oocytes and embryos: use of a mouse model to investigate
      effects upon zona hardness and formulate treatment strategies in an in-vitro
      fertilization programme.
AB  - Mouse oocytes and embryos were obtained following ovulation induction of (C57B16
      x CBA) F1 animals. Zonae pellucidae were exposed to alpha-chymotrypsin in
      phosphate-buffered medium (PB1) supplemented with 3 mg/ml bovine serum albumin
      upon a heated stage (37 degrees C) and were observed constantly through an
      inverted microscope. The endpoint of the bioassay was the limits of the zona no
      longer being seen clearly at x 200 magnification, and the time taken for each
      zona to dissolve was recorded. A dose-dependent response in dissolution time was
      clearly seen, with 1% alpha-chymotrypsin being chosen as the routine working
      solution. Cryopreservation of 2-cell mouse embryos using propanediol did not
      cause zona hardening but induced a small and significant softening, as gauged by
      the time taken for zona dissolution (2181 +/- 167 versus 1864 +/- 82 s). Zona
      hardening was not suspected to occur after the freezing of human embryos as there
      was no difference in implantation rates per embryo for in-vitro fertilization
      (IVF) and intracytoplasmic sperm injection (ICSI) treatment cycles between fresh
      [IVF: 63/644 (9.7%); ICSI: 51/330 (15.5%)] and frozen embryos [IVF: 36/458
      (7.9%); ICSI: 18/112 (16.1%)]. Conversely, significant hardening of the zonae of
      mature oocytes was seen following cryopreservation (747 +/- 393 s) compared with
      freshly ovulated oocytes (151 +/- 68 s). It is concluded that (i) the freezing of
      murine oocytes with propanediol results in zona hardening, implying a possible
      benefit of ICSI after the cryopreservation of human oocytes, and (ii) the
      cryopreservation of embryos is not associated with zona hardening or reduced
      implantation, making microdissection of the zona in such cases generally
      unwarranted.

PMID- 9262295
TI  - A randomized comparison of the cryopreservation of one-cell human embryos with a
      slow controlled-rate cooling procedure or a rapid cooling procedure by direct
      plunging into liquid nitrogen.
AB  - We conducted a randomized prospective study of the cryopreservation of one-cell
      human embryos, comparing a slow controlled-rate freezing procedure with a rapid
      cooling procedure by direct plunging into liquid nitrogen. We analysed the
      numbers of embryos that were recovered immediately after thawing (= recovery),
      the number of embryos morphologically intact after thawing and subsequent
      dilution of the cryoprotectants (= survival), the numbers of embryos undergoing
      further cleavage after 24 h of in-vitro culture (= cleavage) and the implantation
      of transferred embryos (= children born per frozen-thawed embryo transferred). We
      demonstrated that the recovery of embryos was greater after slow controlled-rate
      freezing. Survival was greater after rapid cooling and the number of embryos
      undergoing further cleavage was higher after slow controlled-rate freezing.
      Although the birth rate was twice as high after slow controlled-rate freezing as
      after rapid cooling, this difference was not statistically significant. In
      conclusion, our results show clearly that for the freezing of one-cell human
      embryos, slow controlled-rate freezing is more efficient than rapid cooling.
      Before rapid cooling is used routinely in clinical in-vitro fertilization
      programmes, its safety and reproducibility must be convincingly demonstrated.

PMID- 9262296
TI  - Are there any limits to assisted conception possibilities? Pregnancy and birth
      following oocyte donation and intracytoplasmic injection of spermatozoa obtained
      by percutaneous epididymal aspiration.
AB  - Intracytoplasmic injection of donor oocytes with spermatozoa recovered by
      percutaneous epididymal aspiration resulted in pregnancy and the birth of a
      healthy male infant.

PMID- 9262297
TI  - A preliminary morphometric study on the endometrium from patients treated with
      indomethacin-releasing copper intrauterine device.
AB  - The intrauterine device (IUD) is an effective method of birth control. However,
      IUD-induced uterine bleeding is a major side-effect and always causes
      inconvenience, sometimes even anaemia. It has been reported that oral
      administration of indomethacin could can reduce IUD-induced uterine bleeding. In
      the present study, we investigated whether indomethacin-releasing copper IUD (IR
      Cu-IUD) can prevent insertion-induced uterine bleeding and its mechanism. Nine
      healthy volunteers of reproductive age were selected for the study. Endometrial
      tissues were collected at same menstrual stage prior to and 3-6 months after IR
      Cu-IUD insertion. Endometrial morphology, cell proliferation/differentiation,
      morphometry and activity of complement Factor VIII were examined. No significant
      difference was found in any of the parameters examined in the same patients, both
      prior to and after IR-Cu-IUD insertion. By comparison with data previously
      obtained from the patients who had Cu-IUD insertions, it is clear that IR-Cu-IUD
      markedly reduced IUD-induced uterine bleeding and this reduction is primarily
      contributed by the anti-inflammatory action of indomethacin.

PMID- 9262298
TI  - Low-dose aspirin in prevention of miscarriage in women with unexplained or
      autoimmune related recurrent miscarriage: effect on prostacyclin and thromboxane
      A2 production.
AB  - Early pregnancies in women with a history of recurrent spontaneous abortion (RSA)
      are accompanied by a deficiency in vasodilatory and anti-aggregatory prostacyclin
      (PGI2) and/or overproduction of its endogenous antagonist thromboxane A2 (TXA2).
      We evaluated the effect of a low-dose aspirin (LDA) on PGI2 and TXA2 production
      and on pregnancy outcome in RSA women with and without detectable anticardiolipin
      antibodies (ACA). Of 82 RSA women studied, 66 became pregnant, and of them, 33
      (six with elevated and 27 with normal ACA concentrations) were randomized to
      receive LDA (50 mg/day) and 33 (six with elevated and 27 with normal ACA
      concentrations) to receive placebo (PLA) from a mean of 6.6 days after the missed
      period to delivery. Treatment with LDA inhibited platelet TXA2 production
      similarly in RSA women with and without detectable ACA and with continuing
      pregnancies (7.0 +/- 0.7 ng/ml, LDA group versus 254.5 +/- 37.8 ng/ml, PLA group,
      mean +/- SEM, P < 0.0001) or miscarrying pregnancies (13.8 +/- 3.8 ng/ml compared
      with 233.6 +/- 59.8 ng/ml, P < 0.0001 respectively). Furthermore, LDA decreased
      urinary excretion of the TXA2 metabolite (2,3-dinor-TXB2) both in pregnancies
      which went to term (6.1 +/- 0.6 ng/mmol creatinine, LDA group versus 19.3 +/- 3.0
      ng/mmol creatinine, PLA group, P < 0.0001) or again ended in miscarriage (4.7 +/-
      0.8 ng/mmol creatinine versus 17.3 +/- 4.4 ng/mmol creatinine, P < 0.0001
      respectively), but did not affect the excretion of the prostacyclin metabolite
      (2,3-dinor-6-keto-PGF1alpha). Early pregnancy ultrasound examination revealed a
      living fetus in 58 women. Of these, seven in the LDA group (23.3%, four with
      elevated and three with normal ACA concentrations) and five in the PLA group
      (17.9%, two with elevated and three with normal ACA concentrations; not
      significant) experienced a miscarriage. All infants were healthy, and the
      frequency of growth retardation was similar in both groups (13.0%). One woman in
      the LDA group (4.3%) and three women receiving PLA (13.0%) developed pre
      eclampsia (not significant). Therefore, although treatment with LDA caused a
      desirable biochemical effect, it did not improve pregnancy outcome in RSA women
      with or without detectable ACA.

PMID- 9262299
TI  - Cryopreservation of all prezygotes in patients at risk of severe hyperstimulation
      does not eliminate the syndrome, but the chances of pregnancy are excellent with
      subsequent frozen-thaw transfers.
AB  - In-vitro fertilization patients (n = 15) at risk of ovarian hyperstimulation
      syndrome (OHSS) (oestradiol > or =4500 pg/ml on the day of human chorionic
      gonadotrophin administration and 25 or more follicles of intermediate or large
      size) underwent aspiration of all follicles and cryopreservation of all
      fertilized oocytes at the pronuclear stage. Patients were monitored for up to 2
      weeks post-retrieval. Subsequent transfer of cryopreserved-thawed embryos was
      performed in programmed cycles using exogenous oestrogen and progesterone for
      endometrial preparation. Two patients (13%) developed OHSS necessitating
      hospitalization and vaginal aspiration of ascitic fluid. Two other patients (13%)
      developed moderate OHSS requiring ascitic fluid vaginal aspiration in the office
      setting, with dramatic improvement of the condition. Subsequent transfer of
      cryopreserved-thawed embryos yielded a clinical pregnancy rate of 58% per
      transfer and ongoing or delivery rates of 42 and 67% per transfer and per patient
      respectively. By eliminating pregnancy potential with cryopreservation of all
      prezygotes and examining the pregnancy potential with subsequent cryopreserved
      thawed transfers, it is concluded that OHSS is reduced, but not eliminated for
      patients at risk. Subsequent transfer of cryopreserved-thawed prezygotes in a
      programmed cycle with exogenous steroids yields an excellent pregnancy rate.

PMID- 9262300
TI  - First trimester development of human chorionic villous vascularization studied
      with CD34 immunohistochemistry.
AB  - Normal chorionic villous vascularization is essential for the undisturbed
      development of pregnancy. Defective vasculogenesis may play a role in
      pathological pregnancy. To assess pathological chorionic villous vascularization,
      normal vascularization has to be defined first. Few data are available on this
      topic. The aim of this study was therefore to investigate normal chorionic
      villous vascularization in ultrasound-dated first trimester pregnancies from week
      5 menstrual age to week 12 (n = 41), using quantitative CD34
      immunohistochemistry. Two important processes in chorionic villous
      vascularization were quantitatively illustrated: (i) maturation, reflected by an
      increase of the total number of luminized vessels as opposed to non-luminized
      haemangioblastic cords and (ii) margination, due to a decrease of villous stromal
      area and an increase of total villous vascular area. The percentage of villous
      stromal area occupied by vascular elements (area difference %) increased from
      0.7% in week 5-2.5% in week 10. Therefore, the area of the villous stroma
      occupied by vascular elements increases and the vessels are situated closer to
      the trophoblastic layer suitable for fetal-maternal exchange. There was also a
      trend in increased number of peripheral vessels (2.0 in week 5 to 4.6 in week
      10), supporting both developmental mechanisms. In conclusion, in exactly dated
      normal human first trimester pregnancies, development of the chorionic villous
      vascular system seems to be mostly characterized by maturation of luminized
      vessels from primitive haemangioblastic cords, and margination to a situation of
      peripherally located vessels.

PMID- 9262301
TI  - The spontaneous pregnancy prognosis in untreated subfertile couples: the
      Walcheren primary care study.
AB  - The spontaneous pregnancy prognosis of couples in a primary care situation has
      never been studied. Prognostic models have been developed for referral
      populations only. We wished to develop a prognostic model to estimate the
      likelihood of live birth and the impact of prognostic factors among untreated
      subfertile couples in a primary care situation. With this aim, we conducted a
      cohort follow-up study of 726 couples in the peninsula of Walcheren, a
      geographically isolated, but demographically and socio-economically
      representative area of an industrialized Western society, The Netherlands. Of the
      Walcheren population, 9.9% exhibit subfertility complaints at least once during
      their lifetime. There were 201 live birth conceptions during 9915 months of
      untreated observation. The cumulative rate of conceptions leading to live births
      was 52.5% when all of the untreated observations were considered, and 72.0% in
      the subgroup of 342 couples who remained untreated throughout their follow-up.
      The relevant prognostic factors in this primary care subfertility population
      were: abnormal post-coital test, tubal defect, ovulation defect, and duration of
      subfertility. A prediction score based on these factors would be accurate in
      approximately 76-79% of cases. Live birth prognosis can be estimated with
      sufficient accuracy to be useful in counselling subfertility patients, and in
      planning clinical management.

PMID- 9262302
TI  - Successful oocyte donation after stage 1C serous ovarian cancer.
AB  - A stage 1C serous epithelial cancer was discovered and treated during laparoscopy
      performed for infertility investigation. An immediate in-vitro fertilization
      (IVF) was scheduled to obtain frozen embryos. Oncological treatment was then
      completed by radical surgery (with uterine conservation) and chemotherapy. Two
      years later, the thawed embryos were unsuccessfully transferred. However,
      following oocyte donation, the patient became pregnant and delivered two babies.
      From this observation, the authors discuss the strategy required in cases of
      early ovarian cancer associated with infertility.

PMID- 9262303
TI  - Donor insemination: Dutch parents' opinions about confidentiality and donor
      anonymity and the emotional adjustment of their children.
AB  - Results from a comparative study investigating 38 donor insemination (DI) Dutch
      families with 4-8 year old children are presented. The aims of this study were to
      investigate parents' opinions on the issues of confidentiality and donor
      anonymity, to assess the emotional development of the children, and to examine in
      DI families the association between secrecy with regard to the use of a donor and
      the emotional adjustment of the children. The DI families were compared to
      families with a child conceived by in-vitro fertilization (IVF) and to families
      with a naturally conceived child. Secrecy appeared to be associated with DI and
      not with IVF: 74% of the DI parents intended not to inform the child about the
      way in which she/he was conceived, whereas none of the IVF parents intended to
      keep the secret. Only one set of DI parents and two sets of IVF parents had
      actually told the child. As to donor anonymity, a spread of opinions appeared
      among DI parents; 57% preferred an anonymous donor, 31% would have liked non
      identifying information about the donor, 9% preferred the donor's identity to be
      registered and 3% remained unsure. Parents' major concern was to know more about
      the medical/genetic background of the donor. Mothers and fathers in the DI
      families differed in their opinions concerning the issues of confidentiality and
      donor anonymity: fathers, more often than mothers, were secretive with regard to
      the use of a donor and husbands, more often than their wives, were in favour of
      donor anonymity. With regard to the emotional development of the children, more
      emotional/behavioural problems were revealed among DI children than among
      children who were naturally conceived. No association was found between secrecy
      and the emotional/behavioural adjustment of the children.

PMID- 9262304
TI  - Use of hydrogen peroxide for vaginal contraception.

PMID- 9262305
TI  - Chromosomes of multipronuclear zygotes resulting from ICSI.

PMID- 9262306
TI  - 'Curing' empty follicle syndrome.

PMID- 9262307
TI  - Anything to learn from exceptionally good in-vitro fertilization treatment
      cycles?

PMID- 9262308
TI  - Comparative costs of methotrexate and laparoscopic surgery.

PMID- 9262309
TI  - In-situ hybridization chromosome analysis of XYY and XXY males' spermatozoa.

PMID- 9262310
TI  - Regulation of neuronal and recombinant GABA(A) receptor ion channels by
      xenovulene A, a natural product isolated from Acremonium strictum.
AB  - Xenovulene A (XR368) is a natural product exhibiting little structural
      resemblance with classical benzodiazepines yet is able to displace high-affinity
      ligand binding to the benzodiazepine site of the gamma-aminobutyric acid (GABA)A
      receptor. We have characterized this compound and an associated congener (XR7009)
      by use of radioligand binding and electrophysiological methodologies with native
      neurons and the Xenopus oocyte expression system. Xenovulene A, and the more
      potent XR7009, inhibited [3H]flunitrazepam binding to rat forebrain with Ki
      values of 7 and 192 nM, and 1.7 and 42 nM, respectively, each site accounting for
      approximately 50% of the total specific binding. In cerebellar and spinal cord
      membranes, these ligands identified only single binding sites. These ligands
      demonstrated no intrinsic agonist activity at recombinant GABA(A) receptors
      comprising alpha1beta1gamma2S subunits expressed in Xenopus oocytes, yet at 1
      microM both significantly potentiated the GABA-induced response and reduced the
      GABA EC50 from 10.9 (control) to 5.1 (Xenovulene A) or 2.7 microM (XR7009). The
      rank potency order for enhancement of the 10 microM GABA response is: XR7009
      (EC50, 0.02 microM) > diazepam (0.03) > Xenovulene A (0.05) > flurazepam (0.17).
      The activity of XR368 and XR7009 was reduced by the benzodiazepine antagonist,
      flumazenil, and absent in receptors devoid of the gamma2 subunit. These agents
      exhibited receptor subtype selectivity because alpha3beta1gamma2S receptors were
      less sensitive to these compounds relative to alpha1 subunit-containing
      receptors, whereas alpha6beta1gamma2S receptors were completely insensitive.
      Potentiation of the response to GABA on native GABA(A) receptors in cortical
      neurons substantiates the profile of the novel structures of Xenovulene A and
      XR7009 as specific benzodiazepine agonists.

PMID- 9262311
TI  - Modulation of cocaine- and methamphetamine-induced behavioral sensitization by
      inhibition of brain nitric oxide synthase.
AB  - Evidence suggests the existence of multiple interactions between dopamine,
      glutamate and nitric oxide (NO) in brain structures associated with psychomotor
      stimulation. The present study was undertaken to investigate the effect of the
      relatively selective inhibitor of the neuronal nitric oxide synthase (NOS)
      isoform, 7-nitroindazole (7-NI), on the development of sensitization to the
      locomotor stimulating effect of cocaine and methamphetamine (METH). Male Swiss
      Webster mice that received 15 mg/kg cocaine once a day for 5 days developed a
      marked locomotor sensitization to a challenge cocaine (15 mg/kg) or cross
      sensitization to a challenge METH (0.5 mg/kg) injection given after a 10-day drug
      free period. This treatment also produced a context-dependent sensitization as
      evident by the sensitized response to a challenge saline injection. Pretreatment
      with 7-NI (25 mg/kg) 30 min before cocaine administration (5 days) completely
      blocked the induction of sensitization to cocaine, the cross-sensitization to
      METH and the conditioned locomotion induced by cocaine. 7-NI when given alone,
      either acutely or for 5 days, had no significant effect on the locomotor activity
      of animals. Animals treated with METH (1.0 mg/kg) for 5 days developed marked
      sensitization to challenge METH (0.5 mg/kg), cross-sensitization to challenge
      cocaine (15 mg/kg) and context-dependent locomotion. Pretreatment with 7-NI (25
      mg/kg) attenuated the sensitized response to METH and the cross-sensitization to
      cocaine as revealed after a 10-day drug-free period. However, the METH-induced
      conditioned locomotion was unaffected by the pretreatment with 7-NI. The present
      study supports the role of brain NO in the development of sensitization to both
      psychostimulants, cocaine and METH. However, it appears that the inability of 7
      NI to completely abolish the sensitized responses induced after METH
      administration is the result of the resistible conditioned locomotion caused by
      METH, but not by cocaine.

PMID- 9262312
TI  - Receptor specificity of retinoid-induced epidermal hyperplasia: effect of RXR
      selective agonists and correlation with topical irritation.
AB  - Retinoid induction of epidermal hyperplasia was investigated in hairless mice
      with synthetic ligands for the retinoic acid (RAR) and retinoid X (RXR) nuclear
      receptors. Induction of hyperplasia by all-trans retinoic acid and the RAR
      specific retinoids TTNPB, tazarotene and AGN 190121 varied over a wide range
      (ED50 = 0.2-100 nmol/animal in three daily applications). Potency of induction
      was not directly correlated to receptor-binding affinity, but specificity of
      action could be demonstrated by inhibition with the high-affinity antagonist of
      the RARs, AGN 193109. Although RAR is functionally complexed with RXR in vivo,
      RXR-selective compounds have only weak potency in induction of hyperplasia. The
      ED50 value of the RXR-selective AGN 191701 was 600 nmol/animal compared with an
      ED50 value of 0.2 nmol for the structurally similar RAR-selective TTNPB. SR11237
      and SR11217, also RXR-selective, each have an ED50 value of >1000 nmol. Unlike
      RAR-specific retinoids, RXR-selective retinoids cause only very mild skin flaking
      at high doses. Relative potencies for cumulative topical irritation (flaking and
      abrasion) of both RAR and RXR ligands were well correlated with epidermal
      hyperplasia. These data are consistent with RXR as a silent partner in the RAR
      RXR heterodimer in skin.

PMID- 9262313
TI  - Excitatory gastric motor and cardiovascular effects of endothelins in the dorsal
      vagal complex are mediated through ET(A) receptors.
AB  - We have shown recently that intracisternal administration of endothelin-(ET)1 and
      ET-3 evokes increases in gastric motor function and arterial blood pressure. The
      aim of our study was to investigate whether the dorsal vagal complex (DVC) is a
      medullary site of action for the gastric motor and cardiovascular effects of ET-1
      and to identify the ET receptor subtype through which these effects are mediated.
      ET-1 (0.1-40 pmol/site) and ET-3 (1 and 100 pmol/site) were microinjected into
      the DVC of alpha-chloralose anesthetized rats, while monitoring intragastric
      pressure, contractile activity of greater curvature longitudinal and pyloric
      circular smooth muscle, arterial blood pressure and heart rate. ET-1, at doses of
      0.1 to 40 pmol, increased intragastric pressure and, at doses of 10 and 40 pmol,
      increased pyloric contractile activity and arterial blood pressure. The increases
      in gastric motor function, but not the hypertension, induced by ET-1 (10 pmol) in
      the DVC were completely abolished by bilateral vagotomy. Spinal cord transection
      prevented increases in arterial blood pressure evoked by ET-1 (40 pmol). Because
      only the highest dose of ET-3 (100 pmol), microinjected into the DVC, increased
      intragastric pressure and pyloric contractile activity and no consistent changes
      in cardiovascular functions were noted, we hypothesized that the gastric motor
      and hypertensive responses to endothelins in the DVC are mediated via ET(A)
      receptors. This was supported by the observation that a selective ET(A) receptor
      antagonist, cyclo(-D-Trp-D-Asp-Pro-D-Val-Leu) (BQ-123; 400 pmol), microinjected
      into the DVC 15 min before ET-1 (10 pmol) or ET-3 (100 pmol), completely blocked
      the gastric motor and cardiovascular responses to endothelins. We conclude that
      endothelins act in the brainstem at the level of the DVC to increase intragastric
      pressure and gastric contractile activity via a vagally mediated pathway and that
      both the gastric motor and hypertensive effects of endothelins in the DVC are
      mediated through ET(A) receptors.

PMID- 9262314
TI  - Anticonvulsant and behavioral effects of neuroactive steroids alone and in
      conjunction with diazepam.
AB  - Epilepsy continues to be a significant clinical problem as current medications
      neither adequately control seizures nor are free of untoward side-effects.
      Modulation of the neuroactive steroid site on the gamma-aminobutyric acid (GABA)A
      receptor complex may be an important new direction for pharmaceutical
      interventions in epilepsy. In this study we evaluated the protective actions of
      four neuroactive steroids, 3alpha-hydroxy-5alpha-pregnan-20-one, the 3beta
      methylated analog, ganaxolone (3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20
      one), 3alpha-hydroxy-5beta-pregnan-20-one and Co 2-1068 (3beta
      (4acetylphenyl)ethynyl-3alpha,21-dihydroxy-5beta++ +-20-one-21-hemisuccinate),
      against several standard convulsive tests in male, Swiss-Webster mice. Consistent
      with their GABAergic actions, the neuroactive steroids as well as diazepam and
      phenobarbital dose-dependently protected against clonic convulsions induced by
      pentylenetetrazol; the N-methyl-D-aspartate receptor antagonist, dizocilpine, was
      ineffective. In contrast to diazepam and phenobarbital, however, all of the
      neuroactive steroids and dizocilpine produced full protection against cocaine
      induced convulsions. Some of the neuroactive steroids, as well as dizocilpine,
      were efficacious against the seizures and lethality induced by N-methyl-D
      aspartate. Pregnenolone, a steroid devoid of GABAergic activity, was not
      effective in any of the convulsant models. Although all of the compounds produced
      motor toxicity in high doses as measured by the inverted-screen test, the
      neuroactive steroids demonstrated an equivalent or improved separation between
      anticonvulsant potency and motoric impairment. Inactive doses of the neuroactive
      steroids markedly enhanced the anticonvulsant effects of diazepam against
      pentylenetetrazol without significantly increasing motor toxicity. This adjunct
      treatment resulted in protective indices ranging from 60 to 360 compared to 12
      for diazepam alone. The distinct profile of anticonvulsant activity of the
      neuroactive steroids may be related to their combined actions on gamma
      aminobutyric acid, N-methyl-D-aspartate receptors, or voltage-operated Ca++
      channels. These results help to define the neuroactive steroids as a novel class
      of antiepileptic agents and suggest their potential in clinical practice.

PMID- 9262315
TI  - LU 51198, a highly sulfated, low-molecular-weight heparin derivative, prevents
      complement-mediated myocardial injury in the perfused rabbit heart.
AB  - Evidence is presented that treatment with a highly sulfated low-molecular-weight
      heparin fraction, LU 51198, protects the ex vivo perfused rabbit heart from human
      complement-mediated injury. Hearts from male New Zealand White rabbits were
      perfused under constant flow in the Langendorff mode. After equilibration, normal
      human plasma was added to the perfusate as a source of complement. Either control
      (n = 8) or LU 51198 (0.6 mg/ml; n = 7) was added to the perfusion medium 10 min
      before the addition of human plasma. Hemodynamic variables were obtained for both
      groups before treatment of human plasma. Hemodynamic variables were obtained for
      both groups before treatment (baseline), 10 min after treatment (zero) and after
      the addition of human plasma. Compared to control-treated hearts, variables
      recorded during perfusion with human plasma, including coronary perfusion
      pressure, left ventricular developed pressure, and left ventricular end-diastolic
      pressure, along with a reduction of creatine kinase and potassium efflux, were
      significantly improved in hearts treated with LU 51198 (P < .05). ELISA assays
      were used to analyze lymphatic effluent for the presence of iC3b, Bb and SC5b-9
      proteins derived from the activation of human complement. The increased presence
      of the Bb fragment in the effluent obtained from LU 51198-perfused hearts
      suggests an accelerated dissociation of the convertases responsible for
      complement amplification, an observation that coincided with protection from
      complement-mediated damage in the presence of the glycosaminoglycan. The lysis of
      rabbit red blood cells upon exposure to human plasma was inhibited by LU 51198,
      which is evidence of the drug's ability to modulate complement reactivity. The
      results of this study indicate that a highly sulfated heparin fraction, LU 51198,
      can reduce tissue injury and preserve discordant organ function that otherwise
      would be compromised during activation of the human complement cascade.

PMID- 9262317
TI  - Discriminative stimulus effects of l-alpha-acetylmethadol (LAAM), buprenorphine
      and methadone in morphine-treated rhesus monkeys.
AB  - The discriminative stimulus effects of l-alpha-acetylmethadol (LAAM), l-alpha
      acetylnormethadol (nor-LAAM), l-alpha-acetyldinormethadol (dinor-LAAM),
      buprenorphine and methadone were investigated in morphine-treated (3.2 mg/kg/day)
      rhesus monkeys (n = 3-6) discriminating between saline and naltrexone (0.01
      mg/kg) and responding under a fixed ratio (FR) schedule of stimulus-shock
      termination. Monkeys responded on the naltrexone lever after either the
      administration of 0.01 mg/kg of naltrexone or the substitution of saline for the
      daily dose of morphine (i.e., 27-hr morphine deprived). Morphine dose-dependently
      reversed naltrexone lever responding in morphine-deprived monkeys. Methadone,
      LAAM, nor-LAAM and dinor-LAAM had morphine-like discriminative stimulus effects
      in all monkeys, whereas, buprenorphine had naltrexone-like discriminative
      stimulus effects in three monkeys and morphine-like effects in two monkeys; 24 hr
      after administration, buprenorphine antagonized the effects of morphine in the
      former and antagonized the effects of naltrexone in the latter. The agonist and
      antagonist effects of buprenorphine persisted for more than 6 days. The relative
      duration of action was: buprenorphine > LAAM > nor-LAAM = methadone = dinor-LAAM
      = morphine. That buprenorphine had markedly different discriminative stimulus
      effects in monkeys treated identically with morphine is likely due to the low
      efficacy of buprenorphine and emphasizes the difficulty in predicting the
      behavioral effects of buprenorphine in opioid-dependent individuals. The
      considerably longer duration of LAAM, than either nor-LAAM or dinor-LAAM,
      indicates that the rate of metabolite formation is important for the long
      duration of LAAM and further suggests that variations in metabolic activity among
      individuals might result in differences in the behavioral effects of LAAM.

PMID- 9262316
TI  - Repeated binge exposures to amphetamine and methamphetamine: behavioral and
      neurochemical characterization.
AB  - Stimulant psychosis and addiction are most commonly associated with repeated,
      high-dose binges or runs, typically preceded by a more intermittent pattern of
      stimulant abuse. We previously reported that rats exposed to an escalating dose
      run pattern of amphetamine administration exhibited changes in their behavioral
      response profile that differed both qualitatively and quantitatively from the
      response to either acute or intermittent daily treatment. To determine the
      generality of these effects and characterize further the nature of the behavioral
      and neurochemical changes of this treatment, rats received single daily
      injections of amphetamine (2.5 or 4.0 mg/kg s.c.) or equimolar doses of
      methamphetamine, followed by multiple runs (four daily injections at 2-hr
      intervals) with the pretreatment dose. This treatment resulted in a unique
      behavioral profile, including a profound increase in the relative expression of
      locomotion vs. stereotypy. The markedly enhanced poststereotypy locomotor
      activation was characterized by repeated "burst"-like episodes of ambulation. The
      number of runs required for the emergence of this behavior was dose dependent and
      was similar for the two drugs except that with methamphetamine, there also was a
      marked prolongation of the poststereotypy locomotor response during run
      exposures. During runs, both drugs produced a decline in the caudate but not the
      nucleus accumbens microdialysate dopamine response, whereas only methamphetamine
      produced a decline in the serotonin response that was apparent in both regions.
      The possible relationship between these behavioral and neurochemical changes and
      their implications for high dose patterns of stimulant abuse are discussed.

PMID- 9262318
TI  - Enhancing effects of monohexanoin and two other medium-chain glyceride vehicles
      on intestinal absorption of desmopressin (dDAVP).
AB  - The intestinal absorption enhancement of the nonapeptide [Mpa1,D-Arg8]vasopressin
      (dDAVP) by medium-chain glyceride vehicles was studied using an in vivo rat
      model. Rats were gavaged with dDAVP formulated with three different lipid
      vehicles: (1) monohexanoin, (2) mixed monoglycerides, diglycerides and
      triglycerides of hexanoic acid and (3) monoglycerides, diglycerides and
      triglycerides of octanoic and decanoic acids, and with saline as control. The
      marker absorption into blood and urine was followed for 24 hr. All lipid vehicles
      enhanced the oral bioavailability of dDAVP, but monohexanoin gave the highest
      increase, approximately 10 times that of control. In contrast to dDAVP, the
      stable and more lipophilic nonapeptide analog [Mpa1,D-Tyr(ethyl)2,Val4,D
      Arg8]oxytocin did not show increased urine recovery when formulated with
      monohexanoin. A 2-fold increase in urine recovery of the inert low-molecular
      weight marker [51Cr]EDTA was observed when formulated with monohexanoin. With use
      of the fluorescent marker Evans blue formulated with monohexanoin, an elevated
      accumulation of Evans blue in the mucus layer was observed after incubation in in
      situ loops. No mucosal damage after lipid vehicle gavage was observed by light
      microscopic evaluation. Medium-chain glycerides functioned well as oral
      absorption enhancers of the model peptide dDAVP, and monohexanoin showed the
      highest enhancement capacity. The mechanisms of this enhancement appear to be
      related to a protection against luminal dDAVP degradation, mucoadhesive
      properties of the vehicle and, possibly, an altered epithelial absorption
      pathway.

PMID- 9262319
TI  - Extracellular dopamine and amphetamine after systemic amphetamine administration:
      comparison to the behavioral response.
AB  - To further delineate amphetamine-dopamine pharmacokinetic-pharmacodynamic
      relationships, we examined extracellular levels of dopamine and amphetamine in
      caudate-putamen after the s.c. administration of 8 mg/kg amphetamine. In a
      parallel group of animals, we also assessed caudate-putamen tissue levels of the
      drug. Extracellular concentrations of the transmitter and the drug exhibited
      similar temporal profiles, each achieving maximum concentrations within 30 min of
      drug administration. Tissue levels of amphetamine exhibited a similar, although
      slightly earlier time to maximum levels. The concentrations of amphetamine and
      dopamine in the extracellular fluid and amphetamine in tissue rapidly declined
      with similar rates of elimination. In contrast to the temporal profiles for both
      dopamine and amphetamine, stereotyped behaviors achieved maximum intensity at
      about 60 min. In addition, although transmitter and drug declined almost 10-fold
      from maximum values over the 4-hr interval after amphetamine administration,
      stereotyped behaviors persisted for at least 3 hr before abating. The results of
      these studies confirm our previous observation that the temporal profiles for
      stereotyped behaviors and extracellular dopamine are dissociated, and also extend
      this dissociation to extracellular amphetamine. In addition, although there was a
      close correspondence between dopamine and amphetamine within each experimental
      animal, individual animals exhibited a broad range of maximal dopamine responses,
      suggesting a differential responsiveness to amphetamine.

PMID- 9262321
TI  - Disposition of vessel dilator and long-acting natriuretic peptide in healthy
      humans after a one-hour infusion.
AB  - The present investigation was designed to determine half-lives, distribution
      phases and metabolic clearance of two new cardiac peptide hormones in humans.
      Long-acting natriuretic peptide (LANP) and vessel dilator were infused at 100
      ng/kg of b.wt./min concentrations for 60 min with their respective concentrations
      measured by specific radioimmunoassays in plasma during and for 3 hr after
      infusion. The half-life of vessel dilator was 107 min, whereas the half-life of
      LANP was 28 min. The average time that the respective peptides were retained in
      the body (mean residence time) was 214 +/- 34 min for vessel dilator and 178 +/-
      12 min for LANP, which indicates that they are widely distributed outside the
      initial space (i.e., circulation). The metabolic clearance normalized to 1.73 m2
      body surface area was 241 ml/min for vessel dilator and 249 ml/min for LANP. The
      total body clearance normalized to 1.73 m2 body surface area was 130 ml/min for
      vessel dilator and 293 ml/min for LANP. The significantly (P < .001) longer half
      lives and slower metabolic clearance of LANP and vessel dilator compared with
      atrial natriuretic factor (half-life, 2.5 min, metabolic clearance, 582-2,581
      ml/min/1.7 m2) explain why these peptides circulate at concentrations 15- to 24
      fold higher than atrial natriuretic factor in healthy humans.

PMID- 9262320
TI  - V2 receptor antagonism of DDAVP-induced release of hemostasis factors in
      conscious dogs.
AB  - The synthetic arginine vasopressin (AVP) analog 1-desamino-8-D-arginine
      vasopressin (DDAVP) is used in a variety of hemorrhagic disorders. The present
      experiments were designed to further characterize the mechanism of DDAVP-induced
      release of hemostasis factors. The [3H]AVP-labeled AVP receptor in canine
      renomedullary membranes exhibited an AVP V2 profile because the V2 receptor
      agonist DDAVP displayed similar subnanomolar affinities as the natural hormone
      AVP, whereas the two selective V1a compounds SR 49059 and d(CH2)5Tyr(Me)AVP as
      well as the selective V1b agonist D-Pal and oxytocin were much less potent. The
      rank order of the binding affinities of three V2 receptor antagonists was SR
      121463 (a newly described selective V2 receptor antagonist) > OPC 31260 >>
      d(CH2)5D-Ile2,Ile4AVP. In conscious dogs, DDAVP (0.1-1 microg/kg I.V.) caused a
      dose-related increase (maximum, 43-52% at 30 min) in plasma levels of factor VIII
      (FVIII), von Willebrand factor (vWF) and tissue-type plasminogen activator (t
      PA), but not in levels of plasminogen activator inhibitor-1. A DDAVP-induced
      hemostasis factor release was also observed in bilaterally nephrectomized dogs.
      Pretreatment with SR 121463 inhibited DDAVP-induced (1 microg/kg I.V.) increases
      in FVIII, vWF and t-PA plasma levels in a dose-dependent manner (ID50 = 14.0 +/-
      4.0, 12.4 +/- 3.0 and 16.7 +/- 1.0 microg/kg I.V., respectively). OPC 31260 (300
      microg/kg I.V.) revealed a lower activity than SR 121463, and d(CH2)5[D
      Ile2,Ile4]AVP (30 microg/kg I.V.) was without effect on the DDAVP response.
      Pretreatment with SR 49059 (1 mg/kg I.V.) and SR 27417 (a platelet-activating
      factor receptor antagonist) (1 mg/kg I.V.) had no effect on the DDAVP-induced (1
      microg/kg I.V.) increases in FVIII, vWF and t-PA plasma levels. The present
      results, therefore, strongly suggest that the effect of DDAVP on hemostasis
      factors occurs via a specific interaction with extrarenal V2 receptors.

PMID- 9262322
TI  - Renal excretory responses produced by central administration of opioid agonists
      in ketamine and xylazine-anesthetized rats.
AB  - This study examined the renal excretory responses produced by the intravenous
      (i.v.) infusion of the alpha-2 agonist, xylazine, in ketamine-anesthetized rats.
      In addition, the renal responses produced by the intracerebroventricular (i.c.v.)
      injection of opioid agonists were also examined with use of this anesthetic
      paradigm. In male Sprague-Dawley rats, the i.v. infusion of isotonic saline (55
      microl/min) containing ketamine alone (1.0 mg/kg/min) produced low levels of
      urine flow rate (6.3 +/- 1.3 microl/min/gkw) and urinary sodium excretion (0.28
      +/- 0.08 microeq/min/gkw). However, after adding xylazine (50 microg/kg/min) to
      the ketamine infusate, these renal excretory responses were significantly
      augmented. Steady-state levels of urine flow rate and urinary sodium excretion
      were attained approximately 120 min after starting the xylazine infusion and were
      similar in magnitude to the levels of water and sodium excretion previously
      observed in untreated, conscious rats. In ketamine/xylazine-anesthetized rats,
      the i.c.v. injection of the mu opioid agonist, dermorphin (0.1 nmol/kg), or the
      kappa opioid agonist, U-50488H (1 microg total), produced profound and concurrent
      diuretic and antinatriuretic responses. The pattern (direction and magnitude) of
      these opioid-induced renal excretory responses was similar to those previously
      reported in conscious rats. Together, these results indicate that the i.v.
      infusion of xylazine enhances the renal excretion of water and sodium in ketamine
      anesthetized rats. Moreover, the renal responses produced by i.c.v.
      administration of opioids are similar in ketamine/xylazine-anesthetized and
      conscious rats. Thus, it appears that the ketamine/xylazine infusion protocol may
      provide a valid and useful approach to investigate various aspects of the central
      opioid control of renal function in rats during experimental procedures that
      require anesthesia.

PMID- 9262323
TI  - Estimation of transplacental and nonplacental diphenhydramine clearances in the
      fetal lamb: the impact of fetal first-pass hepatic drug uptake.
AB  - Previous estimates of maternal and fetal placental and nonplacental clearances in
      pregnant sheep using a two-compartment open model have revealed higher values of
      fetal placental clearance (CLfm) compared to the maternal placental clearance
      (CLmf) for most drugs. This includes the antihistamine diphenhydramine (DPHM),
      which also has the highest weight-corrected fetal nonplacental clearance (CLfo)
      among the drugs studied. This study was designed to determine the reasons for
      this CLfm - CLmf difference and to identify the sites of high CLfo for DPHM. DPHM
      and a stable isotope-labeled analog, [2H(10)]DPHM, were simultaneously infused to
      steady state to the mother and fetus, respectively, in five pregnant sheep. CLmf,
      CLfm, CLmo and CLfo averaged 50.3 +/- 13.2, 214.4 +/- 30.8, 36.6 +/- 1.9 and
      109.8 +/- 22.3 ml/min(-1)/kg(-1), respectively. By measuring
      diphenylmethoxyacetic acid and [2H(10)]diphenylmethoxyacetic acid levels in
      samples obtained from our previous study of fetal hepatic first-pass DPHM uptake,
      the hepatic first-pass extraction ratio of the drug from umbilical venous blood
      was estimated to be 0.44 +/- 0.05. This can account for virtually all of CLfo.
      Fetal hepatic first-pass uptake of maternally derived DPHM in the paired infusion
      study reduces the fetal/maternal plasma DPHM concentration ratio and results in
      significant underestimation of CLmf. When the CLmf estimate is corrected for this
      factor and for maternal-fetal DPHM plasma protein binding differences, its value
      approaches CLfm. Fetal hepatic first-pass uptake may also be a factor in the
      underestimation of CLmf for most of the other drugs. Conversely, a lower value of
      CLmf compared with CLfm provides evidence for significant fetal hepatic uptake of
      these compounds.

PMID- 9262324
TI  - Dynorphin A (1-8) analog, E-2078, crosses the blood-brain barrier in rhesus
      monkeys.
AB  - E-2078 is a dynorphin A (1-8) analog, [N-methyl-Tyr1, N-methyl-Arg7-D-Leu8]
      dynorphin A (1-8) ethylamide. Its ability to cross the blood-brain barrier was
      examined in rhesus monkeys using matrix-assisted laser desorption/ionization mass
      spectrometry. In vivo studies were carried out by i.v. injecting E-2078, 10
      mg/kg, a dose that had been found to be antinociceptive, to rhesus monkeys. Blood
      and cerebrospinal fluid samples were collected at various time points after the
      injection. It was found that E-2078 was stable in vivo in rhesus monkey blood. No
      biotransformation products were detected in the blood. Mass spectrometric
      analysis of the cerebrospinal fluid samples collected after E-2078 injection
      detected the presence of E-2078, indicating that E-2078 had crossed the blood
      brain barrier. These findings are consistent with the possibility that
      systemically administered E-2078 could produce centrally mediated behavioral and
      physiological effects.

PMID- 9262326
TI  - Endogenous natriuretic factors 6: the stereochemistry of a natriuretic gamma
      tocopherol metabolite LLU-alpha.
AB  - 2,7,8-Trimethyl-(S)-2-(beta-carboxyethyl)-6-hydroxy chroman (S-LLU-alpha)
      isolated from human uremic urine is apparently an oxidative side-chain
      degradation product of gamma-tocopherol. This compound exhibits natriuretic
      activity in vivo and it appears to mediate the inhibition of the 70 pS K+ channel
      in the apical membrane of the thick ascending limb of the nephron. The
      stereochemistry at the C-2 of LLU-alpha has been unequivocally established to be
      S(+) by X-ray crystallographic analysis of a diastereomeric amide derivative. It
      was also established that the chroman ring oxidation of S-LLU-alpha proceeded
      without racemization at C-2. This finding can be extended to nonepimerization at
      C-2 of alpha-delta tocopherols (Vitamin E) during side-chain oxidation and
      stereospecificity (retention or inversion) of oxidative opening of the chroman
      ring. The resolution of the enantiomers of the parent compound and derivatives
      was accomplished by chiral high-performance liquid chromatography. The
      stereospecific enzymatic hydrolysis by an array of commercially available enzymes
      of the racemic methyl ester of LLU-alpha was investigated. The lipase from
      Humicola languinosa appears to be the best enzyme for resolution by selective
      hydrolysis of the racemic methyl ester.

PMID- 9262325
TI  - Influences of excitatory amino acid receptor agonists on nucleus of the solitary
      tract neurons receiving aortic depressor nerve inputs.
AB  - Neurons in the nucleus of the solitary tract (NTS) of the anesthetized rat were
      classified according to their responses to aortic depressor nerve stimulation:
      monosynaptic neurons (MSNs), polysynaptic neurons (PSNs) and non-aortic depressor
      nerve-evoked neurons (NENs). Agonists for excitatory amino acid (EAA) receptors
      were applied by microiontophoresis at currents of 5 to 40 nA. At these "doses,"
      the nonselective EAA agonist glutamate (100 mM) increased the firing rate of some
      MSNs (5/9), PSNs (6/8) and NENs (16/20) (P < .01 for each group). Some neurons in
      each group were very resistant to glutamate, even at high ejecting currents. In
      addition, most NTS neurons were excited by selective EAA agonists, (RS)-alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (10 mM), kainate (10 mM), N
      methyl-D-aspartic acid (100 mM) and trans-(1S,3R)-1-amino-1,3
      cyclopentanedicarboxylic acid (100 mM). As with glutamate, some NTS neurons in
      each class were also very resistant to selective EAA agonists. Statistical
      analysis indicated that N-methyl-D-aspartic acid, but not (RS)-alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid and kainate, was more potent on PSNs
      than on MSNs or NENs (P < .01 for each comparison). There was a trend for trans
      (1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid to be more potent on MSNs than
      on PSNs or NENs (P = .09 and .07, respectively). Our results suggest that all EAA
      receptor subtypes are involved in baroreceptor afferent integration within NTS,
      and NTS neurons appear to possess different combinations of EAA receptor
      subtypes.

PMID- 9262327
TI  - Endogenous natriuretic factors 7: biospecificity of a natriuretic gamma
      tocopherol metabolite LLU-alpha.
AB  - The structural elucidation and mechanism of action of a potential component, LLU
      alpha, of what is possibly a multifactorial complex known as "natriuretic
      hormone" was recently reported [Wechter, W.J. et al. (1996a) Proc. Natl. Acad.
      Sci. U.S.A. 93: 6002-6007]. "Natriuretic hormone," a long-sought factor, is
      believed to regulate extracellular fluid volume and consequently be pathomimetic
      for hypertension, cirrhosis, congestive heart failure and other volume expanded
      states. The studies reported herein further characterize LLU-alpha. The precursor
      of the endogenous LLU-alpha was demonstrated to be gamma-tocopherol by
      radiolabeling studies. The pharmacokinetics of infused rac-LLU-alpha proved to be
      biphasic (half-lives: 12 min and 6 h). Specificity of the inhibition of the 70 pS
      potassium channel of the thick ascending limb of the loop of Henle was examined
      with the natural S-enantiomer being the most potent known inhibitor whereas the
      analogous alpha-tocopherol metabolite, rac-5-Me-LLU-alpha, showed no inhibition.
      Rac-LLU-alpha does not inhibit two isozymes of the Na+/K+-ATPase. LLU-alpha is
      natriuretic acting via inhibition of the 70 pS potassium channel and not Na+/K+
      ATPase, the assumed mechanism of action of the "natriuretic hormone." LLU-alpha,
      a metabolite of a vitamin, if it were found to play a role in the regulation of
      extracellular fluid volume, would be the second example of a vitamin acting as a
      precursor for a hormone. Of considerable interest is the fact that this
      manuscript reports the first biological activity of gamma-tocopherol, a member of
      the vitamin E complex.

PMID- 9262328
TI  - Pharmacokinetics and tissue distribution of a DNA-methyltransferase antisense (MT
      AS) oligonucleotide and its catabolites in tumor-bearing nude mice.
AB  - The pharmacokinetics of a 20-mer phosphorothioate antisense oligodeoxynucleotide
      was investigated in nude mice bearing a s.c. human lung carcinoma. The
      oligodeoxynucleotide, referred to as DNA-methyltransferase antisense (MT-AS) was
      designed to bind to the mRNA that coded for DNA-methyltransferase, an enzyme that
      controls the extent of methylation of 5'-cytosine. MT-AS was administered at four
      different doses (10, 30, 100 and 300 mg/kg) as an i.v. bolus in a composite study
      design. A maximum of four blood samples were collected from any single animal,
      followed by sacrifice to obtain tissues. The plasma and tissue samples were
      collected from 5 min to 48 h after dosing and were processed by anion-exchange
      HPLC (high performance liquid chromatography) and by capillary gel
      electrophoresis. On the basis of total (i.e., 15-mer to 20-mer species) MT-AS
      plasma concentrations as determined by HPLC, total clearance ranged from 7.9
      ml/min/kg at the 30-mg/kg dose level to 15.2 ml/min/kg at 10 mg/kg; however,
      there were no definitive dose-dependent changes in clearance. The volume of
      distribution at steady state increased from a low value of 379 ml/kg at 30 mg/kg
      to a high of 1983.0 ml/kg at 300 mg/kg, a result that suggests saturable protein
      binding. In vitro plasma protein binding data supported this possibility, because
      the percentage of MT-AS bound decreased at high MT-AS concentrations. MT-AS
      distributed into most tissues, with a general rank order of kidney > liver >
      tumor > lung > muscle > brain. Analysis of plasma samples by capillary gel
      electrophoresis from 2 h to 8 h revealed that about 50% of the total
      oligodeoxynucleotides were due to the parent 20-mer MT-AS; the remainder
      consisted of 15-mer to 19-mer catabolites. Of particular interest was the
      relatively high tumor uptake of MT-AS. These results will support future studies
      designed to characterize the pharmacological action of MT-AS and its efficacy in
      preclinical models.

PMID- 9262329
TI  - Sympathetic neurotransmission in isolated rat atria after sensory-motor
      denervation by neonatal treatment with capsaicin.
AB  - Long-term interactions between sympathetic and sensory-motor nerves have been
      shown in several tissues. Previous investigations in this laboratory have
      demonstrated an increase in cardiac sensory-motor innervation after neonatal
      sympathectomy by guanethidine and an increase of perivascular sympathetic
      neurotransmission after neonatal treatment by capsaicin. The present study
      evaluated the effects of sensory-motor denervation on sympathetic
      neurotransmission in the heart. Newborn rats were injected with capsaicin or its
      vehicle (Tween 80). Sympathetic neurotransmission was studied in isolated atria
      driven at a constant rate (4 Hz) by measuring cardiac responses to electrical
      field stimulation, in the presence of atropine 1 microM. Inotropism of tyramine,
      norepinephrine and calcitonin gene-related peptide was also tested. Neonatal
      capsaicin treatment did not affect cardiac responses to trains of an increasing
      number (2-32) of field pulses. Moreover, inotropic responses to tyramine did not
      differ between control, capsaicin- and Tween 80-treated preparations. Neither
      maximal effect nor pD2 values were significantly different between the groups.
      Similarly, the inotropism of calcitonin gene-related peptide was comparable in
      all groups of atrial preparations. In marked contrast to earlier papers on blood
      vessels, this study shows a lack of effect of sensory-motor denervation by
      neonatal capsaicin treatment on cardiac sympathetic neurotransmission. The
      different neuronal plasticity of vascular and cardiac sensory innervation will be
      discussed. The present results also indicate that capsaicin-induced sensory-motor
      denervation is not associated with changes in cardiac responsiveness to
      calcitonin gene-related peptide.

PMID- 9262330
TI  - Activation of the cloned human kappa opioid receptor by agonists enhances
      [35S]GTPgammaS binding to membranes: determination of potencies and efficacies of
      ligands.
AB  - Activation of kappa receptors inhibits adenylate cyclase, enhances K+ conductance
      and reduces Ca++ conductance via pertussis toxin-sensitive G proteins. We
      recently cloned a human kappa opioid receptor and stably expressed it in Chinese
      hamster ovary (CHO) cells. In this study, the effects of activation of the human
      kappa receptor by agonists on [35S]GTPgammaS binding to CHO cell membranes were
      examined. The presence of GDP and Mg++ was essential for the kappa agonist (-)
      U50,488H-induced increase in [35S]GTPgammaS binding to be observed and the
      optimal concentration was 3 microM and 5 mM, respectively. The presence of 100 mM
      Na+ was necessary to produce the maximal signal-to-background ratio. (-)U50,488H
      induced increase in [35S]GTPgammaS binding was time- and tissue concentration
      dependent. (-)U50,488H increased [35S]GTPgammaS binding in a dose-dependent
      manner with an EC50 of 3.1 nM. (+)-U50,488H had no effect, which indicates that
      this effect is stereospecific. Naloxone (1 microM) or norbinaltorphimine (10 nM)
      shifted the dose-response curve of (-)-U50,488H to the right by 100-fold. These
      results indicate that enhancement of [35S]GTPgammaS binding by (-)-U50,488H is a
      kappa receptor-mediated event. Pretreatment of the cells with pertussis toxin,
      but not cholera toxin, abolished the (-)-U50,488H-induced increase in
      [35S]GTPgammaS binding, which indicates the involvement of Gi and/or Go proteins.
      [35S]GTPgammaS binding induced by (-)-U50,488H had a Kd value of 0.34 +/- 0.08 nM
      and a Bmax value of 431 +/- 29 fmol/mg protein. The rank order of potencies of
      opioid ligands tested in stimulating [35S]GTPgammaS binding was dynorphin A 1-17
      > (+/-)-ethylketocyclazocine > beta-funaltrexamine, (-)-U50,488H, tifluadom >
      nalorphine > pentazocine, nalbuphine > buprenorphine. Dynorphin A 1-17, (+/-)
      ethylketocyclazocine, (-)-U50,488H, tifluadom and beta-funaltrexamine were full
      agonists, but nalorphine and pentazocine were partial agonists producing maximal
      responses of 68% and 23% of those of full agonists, respectively. Nalbuphine and
      buprenorphine had low levels of agonist activities. Norbinaltorphimine and
      naloxone were antagonists devoid of activities. Enhancement of [35S]GTPgammaS
      binding by kappa agonists provides a simple functional measure for receptor
      activation and can be used for determination of potencies and efficacies of
      opioid ligands at the kappa receptor.

PMID- 9262331
TI  - Pharmacokinetic-pharmacodynamic modeling of the antinociceptive effect of
      diclofenac in the rat.
AB  - The relationship between the pharmacokinetics and the antinociceptive effect of
      diclofenac was evaluated using the pain-induced functional impairment model in
      the rat. Male Wistar rats were injected with uric acid in the knee joint of the
      right hind limb, which induced its dysfunction. Once the dysfunction was
      complete, animals received a p.o. dose of 0.56, 1, 1.8, 3.2, 5.6 or 10 mg/kg of
      sodium diclofenac, and the antinociceptive effect and drug blood concentration
      were simultaneously evaluated at selected times for a period of 6 h. Diclofenac
      produced a dose-dependent antinociceptive effect, measured as a recovery of the
      functionality of the injured limb. However, the onset of the antinociceptive
      effect was delayed with respect to blood concentrations. Moreover, the effect
      lasted longer than expected from pharmacokinetic data. Therefore, when
      functionality index was plotted against diclofenac blood concentration, an
      anticlockwise hysteresis loop was observed for all doses. Hysteresis collapse was
      achieved using the effect-compartment model, and the plot of functionality index
      against diclofenac concentration in the effect-compartment data was well fitted
      by the sigmoidal Emax model. Our data suggest slow equilibrium kinetics between
      diclofenac concentration in blood and at its site of action, which leads to a
      delayed onset of the antinociceptive effect as well as a longer duration of the
      response resulting from drug accumulation in synovial fluid.

PMID- 9262332
TI  - BIBP 3226, suramin and prazosin identify neuropeptide Y, adenosine 5'
      triphosphate and noradrenaline as sympathetic cotransmitters in the rat arterial
      mesenteric bed.
AB  - The physiological role of neuropeptide Y (NPY) and extracellular adenosine 5'
      triphosphate (ATP) in sympathetic neurotransmission is becoming increasingly
      clear. To assess whether NPY and ATP act as cotransmitters together with
      noradrenaline (NA) in the sympathetic nerves of the superior mesenteric artery,
      the changes in perfusion pressure of the arterial mesenteric bed caused by nerve
      stimulation were recorded. Depolarization of the perivascular superior mesenteric
      arterial nerves caused frequency- and time-dependent increases in the perfusion
      pressure that were abolished by guanethidine, which implied the sympathetic
      origin of these responses. Independent perfusion with either 500 nM BIBP 3226, an
      NPY Y1 antagonist; 3 microM suramin, a competitive purinoceptor antagonist; or
      0.1 nM prazosin, a competitive alpha-1 adrenoceptor antagonist, evoked
      approximately a 30% reduction in the rise in perfusion pressure caused by the 20-
      to 30-Hz electrical depolarization of the perimesenteric arterial nerves.
      Prazosin (0.1 nM) blocked the increases in perfusion pressure caused by
      electrical stimulation of the perimesenteric nerves but did not significantly
      reduce the vasomotor effect of exogenous NA. Likewise, 5-methyl urapidil and
      chloroethylclonidine, alpha-1 adrenoceptor antagonists with selectivity for the
      alpha-1A and alpha-1B receptor subtypes, respectively, concentration-dependently
      decreased the increase in perfusion pressure elicited by electrical stimulation
      of the perimesenteric nerves at concentrations lower than that required to block
      the vasoconstriction elicited by exogenous NA. The combined perfusion of 3 microM
      suramin plus 0.1 nM prazosin did not result in a complete inhibition of the
      physiological response. Only upon the simultaneous application of BIBP plus
      suramin plus prazosin was the rise in perfusion pressure abolished. These results
      support the working hypothesis that the sympathetic nerves of the rat mesenteric
      bed release NPY, ATP and NA that act as postjunctional cotransmitters in this
      neuroeffector junction.

PMID- 9262333
TI  - Direct injection of 5-HT2A receptor agonists into the medial prefrontal cortex
      produces a head-twitch response in rats.
AB  - The serotonin (5-HT)(2A/2c) agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane
      (DOI), the 5-HT2C agonist 6-chloro-2-[1-piperazinyl]-pyrazine and the 5-HT2A
      partial agonist m-chloro-phenylpiperazine (mCPP) were injected bilaterally into
      the medial prefrontal cortex of male rats. DOI and mCPP, but not 6-chloro-2-[1
      piperazinly]-pyrazine, elicited a dose-dependent head-twitch response (HTR). DOI
      induced HTR had an ED50 of 12.8 nmoles/0.5 microl/side and was inhibited by the 5
      HT2A antagonists ketanserin and MDL 100,907 but was not blocked by pretreatment
      with the selective 5-HT(2C/2B) antagonist SDZ SER 082. The HTR to mCPP
      demonstrated a bell-shaped dose-response curve with an ED50 of 1.5 nmoles/0.5
      microl/side and a peak effect after 3 nmoles/side. The response to mCPP was
      greatly diminished by both ketanserin and MDL 100,907 and was partially reversed
      by SDZ SER 082. These findings suggest that the HTR produced by the direct
      injection of serotonergic agonists into the medial prefrontal cortex is, in part,
      mediated by the activation of 5-HT2A receptors. Pretreatment of rats with the 5
      HT1A agonist (+/-)-8-hydroxy-dipropylaminotetralin hydrobromide inhibited the HTR
      to DOI. This is consistent with other evidence that suggests a functional
      antagonism between 5-HT1A and 5-HT2A receptor activation. The HTR to DOI was
      potentiated by the novel 5-HT1A selective antagonist WAY 100,635, which suggests
      that 5-HT1A receptors tonically regulate this behavioral response to stimulation
      of cortical 5-HT2A receptors.

PMID- 9262334
TI  - Differential action of riluzole on tetrodotoxin-sensitive and tetrodotoxin
      resistant sodium channels.
AB  - The effects of riluzole, a neuroprotective drug, on tetrodotoxin-sensitive (TTX
      S) and tetrodotoxin-resistant (TTX-R) sodium channels in rat dorsal root ganglion
      neurons were studied using the whole-cell patch clamp technique. At the resting
      potential, riluzole preferentially blocked TTX-S sodium channels, whereas at more
      negative potentials, it blocked both types of sodium channels almost equally. The
      apparent dissociation constants for riluzole to block TTX-S and TTX-R sodium
      channels in their resting state were 90 and 143 microM, respectively. Riluzole
      shifted the voltage dependence of activation of TTX-R sodium channels in the
      depolarizing direction more than that of TTX-S sodium channels. The voltage
      dependence of the fast inactivation of both types of sodium channels was shifted
      in the hyperpolarizing direction in a dose-dependent manner, and the apparent
      dissociation constants for riluzole to block the inactivated channels were
      estimated to be 2 and 3 microM for the TTX-S and TTX-R sodium channels,
      respectively, indicating a much higher affinity for the inactivated channels than
      for the resting channels. Riluzole was equally effective in blocking both types
      of sodium channels in their slow inactivated state. Since more TTX-S channels are
      inactivated than TTX-R channels at the resting potential, riluzole blocks TTX-S
      sodium channels more potently than TTX-R sodium channels. It was concluded that
      one of the mechanisms by which riluzole exerts its neuroprotective action is to
      preferentially block the inactivated sodium channel of damaged or depolarized
      neurons under ischemic conditions, thereby suppressing excess stimulation of the
      glutamatergic receptors and massive influx of Ca++.

PMID- 9262335
TI  - Relationship between chemical structure and physicochemical properties of series
      of bulky organic cations and their hepatic uptake and biliary excretion rates.
AB  - To obtain more insight in the relationship between physicochemical properties of
      cationic drugs and their hepatobiliary transport rate, a series of 12
      aminosteroidal neuromuscular blocking agents (NMBAs), supplemented with data of
      four related NMBAs from the literature, were investigated in the isolated
      perfused rat liver. A significant correlation was found between plasma protein
      binding and the partition coefficient octanol/Krebs (log P), confirming results
      from the literature with other organic cations. Evidence was found for a
      saturable hepatic uptake of several NMBAs, indicating that carrier-mediated
      uptake processes are involved. Hepatic uptake rate was closely related to the
      lipophilicity of the compounds; the initial extraction ratio, the apparent
      clearance and the intrinsic clearance were significantly correlated to log P. We
      did not find a significant correlation between biliary clearance and
      lipophilicity in the current series of compounds. Pharmacokinetics analysis of
      perfusate disappearance and biliary excretion data revealed that a considerable
      fraction of the dose of these bulky organic cations is stored in the liver and
      seems to not be directly available for biliary excretion. This finding is in line
      with earlier observations showing a pronounced accumulation of this type of
      compounds in mitochondria and lysosomes.

PMID- 9262336
TI  - Potential antidepressant effects of novel tropane compounds, selective for
      serotonin or dopamine transporters.
AB  - The forced swimming test (FST) predicts the efficacy of clinically effective
      antidepressants. In the present study, using the FST we examined the
      antidepressant potential of three novel tropane analogs: 8-methyl-2beta-propanoyl
      3beta-(4-(1-methylethyl)phenyl)-8-azabicy clo[3.2.1] (WF-31) and 2beta-propanoyl
      3beta-(4-(1-methylethyl)phenyl)-8-azabicyclo[3.2.1 ]octane (WF-50), selective
      inhibitors of serotonin uptake, and 8-methyl-2beta-propanoyl-3beta-(4-(1
      methylphenyl)-8-azabicyclo[3. 2.1] octane (PTT, WF-11), a selective inhibitor of
      dopamine uptake. Fluoxetine and GBR 12909 were used as controls for selective
      inhibitors of serotonin and dopamine, respectively. Drugs were administered three
      times in a 24-hr period between pretest and test sessions. Intraperitoneal
      administration of WF-31 (0.1-10.0 mg/kg), WF-50 (0.3-10.0 mg/kg) and fluoxetine
      (0.3-10.0 mg/kg) dose-dependently decreased immobility while increasing swimming.
      In contrast, WF-11 (0.3-3.0 mg/kg) dose-dependently decreased immobility and
      increased both swimming and climbing, whereas GBR 12909 (3.0-30.0 mg/kg)
      decreased immobility, increased climbing but did not affect swimming. In a
      separate experiment, WF-11 (1.0 mg/kg) increased locomotor activity, whereas a
      higher dose of WF-11 (3.0 mg/kg) and GBR-12909 (30.0 mg/kg) produced stereotypic
      behaviors, suggesting that the effects in the FST may have been attributable to
      increases in general activity. However, the effects of WF-11 on swimming in the
      FST indicate that WF-11 produces antidepressant-like effects in addition to motor
      stimulation. These results confirm previous results that behavioral patterns
      manifested in the FST are characteristic of specific monoamine uptake inhibitors.
      In addition, these results demonstrate that WF-31 and WF-50 produce behavioral
      patterns similar to fluoxetine in the FST without accompanying decreases in motor
      activity, suggesting a potential antidepressant action. Based on comparisons with
      fluoxetine, the data suggest WF-31 and WF-50 may be therapeutically useful as
      potential antidepressant medications.

PMID- 9262337
TI  - Mu opioid agonists potentiate amphetamine- and cocaine-induced rotational
      behavior in the rat.
AB  - Opioids modulate brain dopaminergic function in various experimental paradigms.
      This study used the rotational model of behavior in rats with unilateral 6
      hydroxydopamine-induced lesions of the nigrostriatal pathway to investigate this
      interaction. Doses of two presynaptically acting dopaminergic drugs, amphetamine
      and cocaine, were coadministered with several doses of the mu opioid agonist,
      morphine. Morphine, at 3.0 mg/kg, potentiated rotational behavior induced by each
      dose of the stimulants. To determine the receptor specificity of the actions of
      morphine, the mu opioid agonists buprenorphine, fentanyl, levorphanol,
      meperidine, and methadone, and dextrorphan, the non-opioid isomer of levorphanol,
      were administered alone and with 1.0 mg/kg amphetamine. Each of these drugs, as
      well as morphine, produced circling behavior on its own. All of the mu opioid
      agonists and dextrorphan increased amphetamine-induced turning; the
      coadministration of dextrorphan, levorphanol, meperidine, methadone and morphine
      with amphetamine produced turning greater than predicted by simple additivity. To
      determine whether an opioid receptor was involved in these interactions, the
      opioid antagonist, naltrexone, was administered before the amphetamine/mu opioid
      receptor agonist combination. Naltrexone blocked the potentiating effects of
      morphine, but not those of the other drugs. Moreover, naltrexone alone dose
      dependently increased amphetamine-induced rotational behavior. These studies show
      that some mu opioid receptor agonists can potentiate stimulant-induced rotational
      behavior and that blockade of opioid receptors can also produce a potentiation.
      The role of mu opioid receptors in these effects remains unclear.

PMID- 9262338
TI  - Pharmacological characterization of in vivo properties of putative mixed 5-HT1A
      agonist/5-HT(2A/2C) antagonist anxiolytics. II. Drug discrimination and
      behavioral observation studies in rats.
AB  - To characterize their in vivo 5-hydroxytryptamine (5-HT)2A antagonist properties,
      the ability of the putative mixed 5-HT1A agonists/5-HT(2A,2C) antagonists (N
      (29(4-(2-pyrimidinyl)-1-piperazinyl)ethyl)tricyclo(3.3.1.1(3,7) ) decane-1
      carboxamide (WY-50,324), (2-(4-(4,4-bis(4-fluorophenyl)butyl)-1-piperazinyl)-3
      pyridinecarboxy lic acid hydrochloride (FG5974), 9,10-didehydro-N-(2-propynyl)-6
      methylergoline-8b-carboxamid e (LEK-8804) and trans-1,3,4,a5,10b-hexahydro10
      methoxy-4-propyl-2H-(1)benzopyra nol[3,4-b]pyridine (CGS 18102A) to antagonize
      both head twitches and discriminative stimulus (DS) effects produced by (+/-)-2,5
      dimethoxy-4-iodoamphetamine (DOI) in rats were compared with those of the 5-HT2
      antagonists ketanserin and ritanserin, and the 5-HT1A agonists 8-hydroxy-2-(di-n
      propylamino)tetralin (8-OH-DPAT) and buspirone. All of these compounds produced
      dose-related decreases in DOI-induced head twitches; however pretreatment with
      the 5-HT1A antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2
      pyridinyl)cyclohe xanecarboxamide (WAY-100635) failed to alter the ability of
      ritanserin, ketanserin or CGS 18102A to attenuate DOI-induced head twitches. In
      contrast, WAY-100635 completely blocked the effects of 8-OH-DPAT, buspirone and
      WY-50,324, and partially blocked the effects of LEK-8804, demonstrating that 5
      HT1A agonist properties are involved in the effects of all of the mixed compounds
      except CGS 18102A. In rats trained to discriminate DOI (0.63 mg/kg) from saline
      in a two-lever, FR10 drug discrimination paradigm, ketanserin, ritanserin and CGS
      18102A blocked the DS effects of the training dose by more than 50%. In contrast,
      WY-50,324, FG5974, LEK-8804, buspirone and 8-OH-DPAT, up to doses that completely
      suppressed responding, failed to produce more than a 33% blockade of the DS
      effects of DOI. In vivo 5-HT1A agonist effects were demonstrated by the finding
      that relatively selective- and mixed-5-HT1A agonists produced one or more
      elements of the "serotonin syndrome," i.e., flat-body posture, forepaw treading,
      or lower-lip retraction, and produced high levels of drug-lever selection in rats
      trained to discriminate 8-OH-DPAT (0.16 mg/kg) from saline. Because DOI-induced
      head twitches and DS effects are thought to be mediated by 5-HT2A receptors, the
      results demonstrate that the putative mixed compound, CGS 18102A has prominent 5
      HT2A antagonist properties in vivo, whereas 5-HT2A antagonist effects of WY
      50,324, FG5974 and LEK-8804 could not be clearly identified.

PMID- 9262340
TI  - Sex differences in opioid antinociception.
AB  - Previous studies indicate that mu opioid agonists such as morphine may produce
      greater antinociception in male than in female rodents. The present study was
      designed to investigate the generality of this finding across dose, time and type
      of opioid agonist. In adult female and male Sprague-Dawley rats, time-effect
      curves were obtained for vehicle and three doses each of the mu agonists fentanyl
      and buprenorphine, the kappa agonists (5alpha,7alpha,8alpha)-(-)-N-methyl-[7-(1
      pyrrolidinyl )-1-oxaspiro-(4,5)dec-8-yl]benzeneacetamide (U69,593) and
      bremazocine and the delta agonists [D-Pen2,D-Pen5]enkephalin (DPDPE) and
      deltorphin on the 52 degrees C hot-plate and tail-withdrawal (immersion) assays.
      There were sex differences in the antinociceptive effects of the two kappa
      agonists and the two delta agonists, but the differences were assay-, dose-
      and/or time-dependent. Peak effects of U69,593 on tail withdrawal and DPDPE on
      hot plate tended to occur earlier in females than in males, and bremazocine
      produced greater tail-withdrawal antinociception in females than in males,
      whereas the highest doses of the two delta opioids produced greater hot-plate
      antinociception in males than in females. These results contrast with several
      previous reports showing that male rodents are more sensitive than females to the
      antinociceptive effects of mu and kappa (but not delta) opioids. These
      discrepancies may be caused by the more comprehensive examination of sex
      differences across dose and time used in the present study; sex differences that
      are dose- or time-dependent may not be apparent if a single dose or time point is
      examined. In addition, repeated testing procedures used in the present study may
      produce different results than acute testing procedures would, if female and male
      rats develop opioid tolerance at different rates.

PMID- 9262339
TI  - Behavioral and neurochemical effects of intranigral administration of glial cell
      line-derived neurotrophic factor on aged Fischer 344 rats.
AB  - To investigate the efficacy of glial cell line-derived neurotrophic factor (GDNF)
      in the augmentation of functional dopaminergic (DAergic) indices in aged rats, 24
      month-old Fischer 344 (F344) rats received single intranigral injections of 10
      microg GDNF (in 10 microl phosphate-buffered saline) or 10 microl phosphate
      buffered saline. In locomotor activity tests, the GDNF-treated animals exhibited
      significant increases in both total distance traveled and movement speed compared
      with the vehicle group, 3 weeks after injections. In vivo microdialysis studies
      showed that basal extracellular levels of dopamine (DA) and its metabolites, 3,4
      dihydroxyphenylacetic acid and homovanillic acid, were significantly increased in
      the striatum of the GDNF-treated rats. In addition, both potassium- (100 mM, K+)
      and d-amphetamine (250 microM)-induced DA overflow were augmented in the striatum
      and nucleus accumbens of the aged rats injected with GDNF. Whole-tissue levels of
      DA and DA metabolites, as measured by high-performance liquid chromatography
      coupled with electrochemical detection, in the nucleus accumbens and substantia
      nigra were also elevated after GDNF administration. These results indicate that a
      single intranigral injection of GDNF is capable of augmenting locomotor behavior
      and DAergic function in the aged rat striatum and nucleus accumbens. This is the
      first report to demonstrate that a single intranigral injection of GDNF can
      improve the functional capacity of DAergic neurons of aged F344 rats.

PMID- 9262341
TI  - Influence of renal failure on the disposition of morphine, morphine-3-glucuronide
      and morphine-6-glucuronide in sheep during intravenous infusion with morphine.
AB  - The influence of experimentally induced renal failure on the disposition of
      morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) was
      examined in seven sheep infused intravenously with morphine for 6 hr. Between 5
      and 6 hr, blood was collected from the aorta, pulmonary artery, hepatic, hepatic
      portal and renal veins and posterior vena cava. Additional samples from the aorta
      and urine were collected up to 144 hr. Morphine, M3G and M6G were determined in
      plasma and urine by high-performance liquid chromatography. Constant
      concentrations of morphine, but not of M3G and M6G, were achieved in plasma
      between 5 and 6 hr. Significant (P < .001) extraction of morphine by the liver
      (0.72 +/- 0.05) and kidney (0.42 +/- 0.15) occurred. Compared with sheep with
      normal kidneys (Milne et al., 1995), renal failure did not alter (P = .11) the
      mean total clearance of morphine (1.5 +/- 0.3 liters/min); clearance by the
      kidney was less (P < .001). However, a paired comparison using sheep common to
      this study and from the study when their kidneys were normal revealed a
      significant reduction in mean total clearance of 25%. The renal extraction of M3G
      and M6G and urinary recovery of the dose as summed morphine, M3G and M6G were
      reduced by renal failure. The kidney metabolized morphine to M3G. The data
      suggest that nonrenal elimination of M3G becomes more important during renal
      failure.

PMID- 9262342
TI  - Enduring enhancement of amphetamine sensitization by drug-associated
      environmental stimuli.
AB  - We report on the effect of environment on amphetamine sensitization in rats with
      a unilateral 6-hydroxydopamine lesion of the mesostriatal dopamine system. The
      rats were either housed in the test environment (HOME) or exposed to it only
      during the treatments (NOVEL). In experiment 1, the rats received seven
      consecutive i.p. injections of either saline or 2 mg/kg amphetamine. After 1 wk
      withdrawal the rotational response to 2 mg/kg amphetamine i.p. (i.e., amphetamine
      challenge) was compared in saline- vs. amphetamine-pretreated animals. Although
      both HOME and NOVEL groups sensitized, the magnitude of sensitization was greater
      in the NOVEL group. In the NOVEL group there was also a greater conditioned
      response to drug-related cues. In experiment 2 a dose-effect curve (0.75, 1.5,
      3.0 and 6.0 mg/kg amphetamine i.p.) was determined before and after six i.p.
      injections of 4.0 mg/kg amphetamine. Sensitization was indicated by a parallel
      shift to the left of the dose-effect curve in both groups, but this shift was 2.6
      times greater in the NOVEL group than in the HOME group. Finally, in experiment
      3, we found that environment- and sensitization-dependent differences in the
      psychomotor response to amphetamine were not accompanied by differences in the
      concentration of amphetamine in the plasma or in the striatum.

PMID- 9262343
TI  - The relationship between the disposition and immunogenicity of sulfamethoxazole
      in the rat.
AB  - Idiosyncratic toxicity associated with sulfamethoxazole (SMX) is thought to be a
      consequence of bioactivation to the hydroxylamine metabolite (SMX-NOH) and
      further oxidation to the ultimate reactive metabolite, nitroso-sulfamethoxazole
      (SMX-NO). To establish the link between the formation of the ultimate reactive
      metabolite and SMX hypersensitivity, we have undertaken metabolism and
      immunogenicity studies in the rat by use of SMX and its metabolites. SMX was
      excreted in urine as N4-acetyl SMX and SMX-NOH, with approximately 10% remaining
      unchanged as parent amine. After administration of SMX-NOH (54 mg x kg(-1)) and
      SMX-NO (10 mg x kg(-1)), 38.3% and 46.1% of the doses, respectively, were
      excreted in urine as SMX and N4-acetyl SMX, which indicated extensive reduction
      of these metabolites in vivo. The immunogenic potential of SMX and its
      metabolites, SMX-NOH and SMX-NO, were assessed in rats by analyzing serum samples
      for the presence of anti-SMX IgG antibodies during a 4-week dosing period. No
      antibodies to SMX were detected in either control or SMX-treated rats. In
      contrast, a high titer of SMX-specific IgG antibody was present in sera from all
      the rats administered SMX-NO, reaching a maximum 14 to 21 days after the initial
      dose. Rats administered SMX-NOH only produced a weak IgG response after 3 weeks
      of dosing. These findings indicate that SMX-NO is highly immunogenic and may be
      responsible for the hypersensitivity reactions associated with SMX. Both SMX-NOH
      and SMX-NO undergo extensive reduction in vivo which may afford protection
      against SMX toxicity.

PMID- 9262344
TI  - Susceptibility to lidocaine of impulses in different somatosensory afferent
      fibers of rat sciatic nerve.
AB  - Mechanosensitive A beta-fibers (n = 29) and nociceptive A delta- (n = 6) and C
      fibers (n = 10) of the rat sciatic nerve were superfused with lidocaine (LID, 0.1
      1.4 mM) in vivo. The [LID] to abolish single electrically stimulated impulses
      (tonic blockade) in axons was 0.2 to 0.8 mM for A beta-, 0.1 to 0.6 mM for A
      delta- and 0.1 to 1.4 mM for C-fibers. Within each of the fiber groups there was
      no dependence of blocking [LID] on conduction velocity; slower fibers were no
      more susceptible than faster ones. Mean blocking concentrations differed between
      groups, with C-fibers having an IC50 = 0.80 +/- 0.32 mM (+/- S.E.), significantly
      higher (P < .05, ANOVA) than A beta-fibers (IC50 = 0.41 +/- 0.15 mM) and A delta
      fibers (IC50 = 0.32 +/- 0.18 mM). The [LID] causing 50% impulse failure in A beta
      fibers during a 200-Hz, 10-stimulus train (phasic blockade) ranged from 0.2 mM to
      0.7 mM; the mean IC50 equaled 0.28 mM (n = 17). Stimulation of nociceptive A
      delta-fibers (n = 4) and C-fibers (n = 5) at 5 or 10 Hz for 10 pulses produced no
      phasic block at [LID]s (0.1-0.5 mM) below those required for tonic blockade.
      Uptake of 14C-lidocaine by the nerve, measured in vivo under conditions identical
      with those for electrophysiology, showed that: a) little drug was in the segments
      of nerve beyond the superfusion chamber, b) lidocaine was uniformly distributed
      in the nerve within the chamber, c) the intraneural lidocaine content was
      identical with that in nerves equilibrated in vitro. The results show a lack of
      monotonic dependence of sensitivity to local anesthetic on fiber diameter, but do
      suggest that mean susceptibility to nerve block by lidocaine differs for fibers
      grouped by, and perhaps according to, function.

PMID- 9262345
TI  - Studies on the tight-binding nature of tolcapone inhibition of soluble and
      membrane-bound rat brain catechol-O-methyltransferase.
AB  - Catechol-O-methyltransferase (COMT) is an enzyme that plays an important role in
      the inactivation of catecholamine neurotransmitters. Experimental and clinical
      data suggest that COMT inhibitors may be useful in Parkinsonian patients. Among
      COMT inhibitors, nitrocatechol derivatives are the most potent and selective. In
      this study, we evaluated the kinetics of rat brain COMT, as well as its
      mechanisms of inhibition by tolcapone. Rat whole-brain homogenates and the
      corresponding soluble and membrane-bound fractions were evaluated for their
      epinephrine 3-O-methylating activity. Tolcapone exhibited a very low IC50 in all
      the three enzyme preparations. In whole-brain homogenates, saturation curves made
      in the presence of 1 nM tolcapone displayed, when compared with controls, a
      reduction in Vmax without changes in Km, which suggested a noncompetitive type of
      inhibition. This was confirmed by experiments in which the IC50 value for
      tolcapone was not affected by substrate concentration. Nevertheless, this classic
      kinetic analysis is not suitable for a tight-binding inhibitor. A very low IC50,
      an inhibition potency that is dependent on the previous contact time of the
      inhibitor with the enzyme and an enzyme titrating capacity were the three
      criteria that tolcapone met as a tight-binding inhibitor in the rat brain. In
      conclusion, our results show that tolcapone is a highly potent tight-binding
      inhibitor of brain soluble and membrane-bound COMT, but because of difficulties
      in determining the type of inhibition for this type of compound, we cannot
      confirm previous claims about the competitive type of COMT inhibition produced by
      tolcapone.

PMID- 9262346
TI  - Striatal acetylcholine release correlates with behavioral sensitization in rats
      withdrawn from chronic amphetamine.
AB  - Stimulant sensitization is defined as an enhancement of the behavioral response
      to drug after repeated drug exposure. We have examined the relation between the
      expression of behavioral sensitization and the release of the striatal
      neurotransmitters acetylcholine (ACh) and dopamine (DA). Rats were treated with
      amphetamine (4 mg/kg i.p., b.i.d.) for 12 days. The behavioral response to
      amphetamine challenge was assessed during the chronic treatment, at short
      withdrawal (2 days) and at long withdrawal (2-3 wk) from the drug. Neurochemical
      responses to amphetamine challenge were assessed in separate groups of rats at
      the two withdrawal timepoints using in vivo microdialysis. The expression of
      behavioral sensitization in response to a low challenge dose of amphetamine (0.5
      mg/kg) was only observed after long withdrawal; indeed, tolerance was observed at
      the short withdrawal timepoint. In contrast, sensitization of the behavioral
      response to challenge with 4 mg/kg amphetamine developed progressively over the
      course of drug treatment and continued to increase throughout withdrawal.
      Striatal ACh release was enhanced by amphetamine challenge (4 mg/kg) in the
      chronically treated animals and this response also was greater at long withdrawal
      vs. short withdrawal. However, amphetamine administration had no net effect on
      striatal ACh release in animals previously given chronic saline injections.
      Amphetamine challenge increased striatal DA release but this response did not
      differ between drug- or saline-treated animals at either withdrawal timepoint.
      Thus, an enhancement of the drug-induced stimulation of striatal ACh release
      correlates with the temporal profile of the expression of behavioral
      sensitization to amphetamine. In contrast, amphetamine-induced DA release does
      not appear to correlate with the expression of behavioral sensitization in the
      same manner.

PMID- 9262347
TI  - Interactions of the neurosteroid dehydroepiandrosterone sulfate with the GABA(A)
      receptor complex reveals that it may act via the picrotoxin site.
AB  - The interactions of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone
      sulfate (DHEAS) were investigated with various binding sites of the gamma
      aminobutyric acid (GABA(A)) receptor complex to rat brain membranes, and on GABA
      induced [36Cl-] influx in mammalian cortical cultured neurons. DHEAS and DHEA did
      not affect the binding of [3H]flunitrazepam to the benzodiazepine binding sites.
      In contrast, DHEAS, but not DHEA, inhibited the binding of [3H]GABA and [35S]TBPS
      to rat brain cerebral cortical and cerebellar membranes in a concentration
      dependent manner. DHEAS decreased the Bmax values of both the high and low
      affinity GABA receptor binding sites without affecting their affinity constants.
      In contrast, DHEAS inhibited [35S]TBPS binding competitively, as analyzed by
      Scatchard analysis. In dissociation kinetic studies, DHEAS dissociated [35S]TBPS
      from rat cerebral cortical membranes in a monophasic pattern that was similar to
      that observed with inhibitors of GABA(A) receptors such as TBPS and picrotoxin
      but different from pentobarbital and GABA. Taken together, these results suggest
      that DHEAS binds to the TBPS/picrotoxin site of the GABA(A) receptor complex, and
      this interaction may be responsible for the noncompetitive inhibition of GABA
      responses observed with DHEAS. Furthermore, we confirmed that DHEAS inhibits GABA
      responses, as measured by GABA-induced [36Cl-] influx in cultured cortical
      neurons. Studies with DHEA indicate that this neurosteroid does not interact with
      the GABA(A) receptor complex.

PMID- 9262348
TI  - Rapid and reversible effects of methamphetamine on dopamine transporters.
AB  - Reactive oxygen species decrease dopamine transporter (DAT) function in vitro.
      Because of this, and the finding that METH administration causes oxygen radical
      formation in vivo, the effects of METH administration on DAT activity in rat
      striatum were investigated. A single METH injection caused a dose-dependent (0-15
      mg/kg) decrease in [3H]dopamine uptake into striatal synaptosomes prepared 1 h
      after METH administration; an effect attributable to a decreased Vmax of
      [3H]dopamine uptake. Similarly, multiple high-dose administrations of METH (10
      mg/kg/dose; four doses at 2-h intervals) decreased DAT function. The decreases in
      DAT activity after either single or multiple METH administrations were reversed
      24 h after treatment. [3H]5HT transport into striatal synaptosomes was also
      affected by METH treatment. Taken together, these data suggest that METH
      decreases DAT activity, perhaps through a reactive oxygen species-mediated
      mechanism. These findings may have important implications regarding the role of
      oxidative events in the physiological regulation of monoaminergic systems.

PMID- 9262349
TI  - Promethazine affects autonomic cardiovascular mechanisms minimally.
AB  - Promethazine hydrochloride, Phenergan, is a phenothiazine derivative with
      antihistaminic (H1), sedative, antiemetic, anticholinergic, and antimotion
      sickness properties. These properties have made promethazine a candidate for use
      in environments such as microgravity, which provoke emesis and motion sickness.
      Recently, we evaluated carotid baroreceptor-cardiac reflex responses during two
      Space Shuttle missions 18 to 20 hr after the 50 mg intramuscular administration
      of promethazine. Because the effects of promethazine on autonomic cardiovascular
      mechanisms in general and baroreflex function in particular were not known, we
      were unable to exclude a possible influence of promethazine on our results. Our
      purpose was to determine the ground-based effects of promethazine on autonomic
      cardiovascular control. Because of promethazine's antihistaminic and
      anticholinergic properties, we expected that a 50-mg intramuscular injection of
      promethazine would affect sympathetically and vagally mediated cardiovascular
      mechanisms. Eight healthy young subjects, five men and three women, were studied
      at rest in recumbency. All reported drowsiness as a result of the promethazine
      injection; most also reported nervous excitation, dry mouth, and fatigue. Three
      subjects had significant reactions: two reported excessive anxiety and one
      reported dizziness. Measurements were performed immediately prior to injection
      and 3.1 +/- 0.1 and 19.5 +/- 0.4 hr postinjection. We found no significant effect
      of promethazine on resting mean R-R interval, arterial pressure, R-R interval
      power spectra, carotid baroreflex function, and venous plasma catecholamine
      levels.

PMID- 9262350
TI  - Influence of oral S-adenosylmethionine on plasma 5-methyltetrahydrofolate, S
      adenosylhomocysteine, homocysteine and methionine in healthy humans.
AB  - Elevated plasma homocysteine concentration is an independent risk factor for
      vascular disease in humans. In addition to nutritional and genetic factors, an
      interruption of the coordinate regulatory function of S-adenosylmethionine has
      been proposed to be involved in the occurrence of hyperhomocysteinemia. The
      effect of oral S-adenosylmethionine on homocysteine metabolism in humans is
      unknown. We investigated the effect of oral S-adenosylmethionine (400 mg) on
      plasma levels of 5-methyltetrahydrofolate, which is the active form of folate in
      the remethylation of homocysteine to methionine, S-adenosylhomocysteine, the
      demethylated product of S-adenosylmethionine, homocysteine and methionine over 24
      hr in 14 healthy subjects. After oral administration, S-adenosylmethionine
      increased from 38.0 +/- 13.4 to 361.8 +/- 66.4 nmol/liter (mean +/- S.E., P <
      .001) and returned to base-line values with a half-life of 1.7 +/- 0.3 hr. Both S
      adenosylhomocysteine and 5-methyltetrahydrofolate showed a significant transient
      increase (from 29.9 +/- 3.7 to 51.7 +/- 7.1 nmol/liter, and from 25.1 +/- 2.5 to
      36.2 +/- 3.5 nmol/liter, respectively, P < .001), although homocysteine and
      methionine did not change over the time of measurement. These changes were not
      found in subjects without previous S-adenosylmethionine administration. The
      observed metabolic changes suggest that S-adenosylmethionine, at least in
      concentrations obtained in this study, does not inhibit 5,10
      methylenetetrahydrofolate reductase, the 5-methyltetrahydrofolate forming enzyme.
      Rather they indicate a positive effect on 5-methyltetrahydrofolate, a key
      cofactor in homocysteine metabolism, which should be considered in homocysteine
      lowering strategies for the prevention of vascular disease.

PMID- 9262351
TI  - Effect of low density lipoprotein on adenosine receptor-mediated coronary
      vasorelaxation in vitro.
AB  - We investigated the effect of low density lipoprotein (LDL) on vasorelaxations
      and nitric oxide generation induced by the adenosine analogs, 5'-(N
      ethylcarboxamide)adenosine, 2-p-(2-carboxyethyl)phenylethyl-amino-5'N
      ethylcarboxamidoadenosine and/or 2-chloroadenosine in porcine coronary artery
      rings in vitro. Preincubation of tissues with native LDL (100 and 200 microg/ml)
      for 4 hr in the absence or presence of copper sulfate (5 microM) selectively
      attenuated the endothelium-dependent relaxations elicited by 5'-(N
      ethylcarboxamide)adenosine and 2-p-(2-carboxyethyl)phenylethyl-amino-5'N
      ethylcarboxamideoadenosine+ ++ without altering the response to 2-chloroadenosine
      which produced endothelium-independent relaxation. The 4-hr exposure of tissues
      to native LDL (100 microg/ml) also inhibited the production of nitrite induced by
      5'-(N-ethylcarboxamide)adenosine in endothelium-intact rings. These effects were
      associated with enhanced oxidation of the lipoprotein. The inhibitory action of
      LDL on tissue relaxations and nitrite generation as well as the oxidation of the
      lipoprotein were all prevented by high density lipoprotein (100 microg/ml). In
      contrast, a relatively short period (20 min) of tissue incubation with native LDL
      produced no alterations of the relaxations and nitrite production evoked by 5'-(N
      ethylcarboxamide)adenosine and 2-p-(2-carboxyethyl)phenylethyl-amino-5'N
      ethylcarboxamidoadenosine. Under this condition, the oxidation of LDL was not
      also significantly altered. In conclusion, the results indicate that in coronary
      artery LDL, with oxidative modification, causes attenuation of nitric oxide
      mediated endothelial responses induced by adenosine receptors activation, and
      this effect is prevented by high density lipoprotein. Such modulation may be of
      importance in hypercholesterolemia and in the development of atherosclerosis.

PMID- 9262352
TI  - Pharmacological characterization of orphanin FQ/nociceptin and its fragments.
AB  - The cloning of a fourth member of the opioid receptor family has led to the
      discovery of a new neuropeptide termed orphanin FQ or nociceptin (OFQ/N). Studies
      in CD-1 mice confirm the ability of OFQ/N to rapidly induce hyperalgesia within
      15 min which is insensitive to opioid antagonists. This is followed in the next
      30 min by loss of hyperalgesia and the appearance of analgesia in the tailflick
      assay which is readily reversed by opioid antagonists. However, the very poor
      affinity of OFQ/N for all the traditional opioid receptors and the insensitivity
      of OFQ/N analgesia to antisense oligodeoxynucleotides active against MOR-1, DOR-1
      or KOR-1 sequences that selectively block mu, delta or kappa1 analgesia,
      respectively, make it unlikely that OFQ/N analgesia is mediated through typical
      opioid receptors. Blockade of the antiopioid sigma system by haloperidol enhances
      the analgesic potency of OFQ/N of more than 100-fold. This effect is pronounced
      in BALB-C and Swiss-Webster mice. Although OFQ/N alone has little analgesic
      activity in these mice, the blockade of sigma systems with haloperidol uncovers a
      robust analgesic response in both strains. Two shorter OFQ/N fragments, OFQ/N(1
      7) and OFQ/N(1-11), also are analgesic in CD-1 mice and their actions are
      reversed by the opioid antagonist diprenorphine despite very poor affinities of
      both peptides against [125I]OFQ/N binding and all the opioid receptors. In
      antisense studies, a probe targeting the first coding exon of KOR-3 eliminates
      OFQ/N hyperalgesia, but not OFQ/N analgesia. Conversely, antisense probes based
      on the second and third coding exons are inactive against OFQ/N hyperalgesia but
      readily reverse kappa3 opioid analgesia. These results suggest that OFQ/N elicits
      both analgesia and hyperalgesia through pharmacologically distinct receptors that
      do not correspond to traditional opioid receptors.

PMID- 9262353
TI  - Kinetic analysis of the primary active transport of conjugated metabolites across
      the bile canalicular membrane: comparative study of S-(2,4-dinitrophenyl)
      glutathione and 6-hydroxy-5,7-dimethyl-2-methylamino-4-(3
      pyridylmethyl)benzothiazole glucuronide.
AB  - Eisai hyperbilirubinemic rat (EHBR) is a mutant strain with a hereditary defect
      in canalicular multispecific organic anion transporter (cMOAT). We examined the
      uptake and mutual inhibition of S-(2,4-dinitrophenyl)-glutathione (DNP-SG), which
      is a typical substrate for cMOAT, and 6-hydroxy-5,7-dimethyl-2-methylamino-4-(3
      pyridylmethyl) benzothiazole (E3040) glucuronide (E-glu) with canalicular
      membrane vesicles (CMV) prepared from Sprague-Dawley (SD) and EHBR rats to
      investigate the multiplicity of the organic anion transporter. The ATP-dependent
      uptake by CMV from SD rats had an apparent Km of 17.6 microM for DNP-SG and 5.7
      microM for E-glu, whereas the corresponding uptake by CMV from EHBR had an
      apparent Km of 44.6 microM for E-glu. The effects of E-glu, 4-methylumbelliferone
      glucuronide (4 MUG), E3040 sulfate (E-sul) and 4-methylumbelliferone sulfate (4
      MUS) on the uptake of [3H]DNP-SG were also examined. The uptake of [3H]DNP-SG was
      inhibited by glucuronides (E-glu and 4 MUG) in a concentration-dependent manner,
      although it was enhanced by the sulfate conjugates (E-sul and 4 MUS). This
      enhancement was shown to be caused by an increased DNP-SG affinity for the
      transporter. In CMV from SD rats, although ATP-dependent uptake of [3H]DNP-SG was
      almost completely inhibited by E-glu, that of [14C]E-glu was only reduced to
      about 30% of controls by DNP-SG. On the other hand, in CMV from EHBR, the ATP
      dependent uptake of [14C]E-glu was not inhibited at all by DNP-SG. Kinetic
      analysis indicated that E-glu inhibited DNP-SG uptake competitively. IN
      CONCLUSION: 1) cMOAT recognizes both DNP-SG and E-glu, and another transporter
      present in SD rats is also involved in E-glu transport along with cMOAT; 2) the
      latter transporter is kinetically similar to the E-glu transporter present in
      EHBR; 3) E-sul enhances the uptake of DNP-SG by increasing the affinity of
      glucuronide for the transporter.

PMID- 9262354
TI  - The effect of central angiotensin II receptor blockade on interleukin-1beta- and
      prostaglandin E-induced fevers in rats: possible involvement of brain angiotensin
      II receptor in fever induction.
AB  - We investigated the role of the brain angiotensin II (Ang II) receptor subtypes
      AT1 and AT2 in the development of fever induced in freely moving rats by
      administration of interleukin-1beta (IL-1beta) or prostaglandin E2 (PGE2).
      Intraperitoneal (i.p.) injection of IL-1beta (2 microg/kg) induced a marked fever
      of rapid onset. Intracerebroventricular (i.c.v.) administration, immediately
      before IL-1beta injection, of a selective AT2 receptor antagonist, CGP42112A (5
      or 20 microg), reduced the fever in a dose-related manner. Rats given an i.c.v.
      injection of PGE2 (200 ng) developed a monophasic fever response that was
      attenuated by i.c.v. treatment with CGP42112A (10 or 20 microg) in a dose-related
      manner. The IL-1beta (2 microg/kg i.p.)- and PGE2 (200 ng i.c.v.)-induced fevers
      were unchanged by the selective AT1 receptor antagonist losartan (60 microg
      i.c.v.). Treatment with exogenous Ang II (100 ng i.c.v.), which itself had no
      effect on resting body temperature, resulted in an enhancement of the PGE2 (50 ng
      i.c.v.)-induced fever. The administration of CGP42112A (2 and 5 microg) into the
      rostral hypothalamus (preoptic/anterior hypothalamic region) reduced fevers
      induced by IL-1beta (2 microg/kg i.p.) or intrahypothalamic (i.h.) PGE2 (100 ng).
      Moreover, i.h. injection of Ang II (25 ng) augmented the PGE2 (25 ng i.h.)
      induced fever. Finally, the i.h. administration, 15 min before i.h. PGE2 (100
      ng), of the angiotensin-converting enzyme (ACE) inhibitor lisinopril (5 and 10
      microg) attenuated the PGE2-induced fever. These results suggest that brain AT2
      receptors contribute to the induction of such febrile responses in rats.

PMID- 9262355
TI  - Possible mechanism of action of AE0047, a calcium antagonist, on triglyceride
      metabolism.
AB  - We evaluated the effect of AE0047, a dihydropyridine-type calcium antagonist, on
      the plasma lipid levels of obese Zucker rats. In rats treated orally with 3 to 10
      mg/kg/day AE0047 for 7 days, plasma triglyceride (TG) and TG-rich lipoprotein
      levels dose-dependently decreased, whereas those of high-density lipoprotein
      cholesterol increased. Total cholesterol and low-density lipoprotein levels did
      not change. To elucidate the mechanism by which AE0047 decreases plasma TG
      levels, we examined the effect of AE0047 on the synthesis and secretion of TG
      rich lipoproteins in human intestinal cell line Caco-2, as well as on the
      association and degradation of very low density lipoprotein (VLDL) in human
      hepatoblastoma cells HepG2. When Caco-2 cells were grown on a membrane filter and
      14C-oleic acid was added to the apical side, 10(-5) and 10(-6) M AE0047 inhibited
      basolateral secretion of 14C-TG. AE0047 also suppressed the basolateral secretion
      of apolipoprotein B. In HepG2 cells, AE0047 increased the cellular uptake of 125I
      VLDL. These results suggested that AE0047 decreased plasma TG level by the
      inhibition of intestinal chylomicron secretion and the enhancement of hepatic
      uptake of VLDL. AE0047 may be beneficial for the treatment of hypertensive
      patients with hypertriglyceridemia to reduce the risk factors of coronary heart
      disease.

PMID- 9262356
TI  - Relationships between pharmacokinetics and blockade of agonist-induced prostatic
      intraurethral pressure and mean arterial pressure in the conscious dog after
      single and repeated daily oral administration of terazosin.
AB  - The purpose of this study was to determine the potency and selectivity of the
      alpha-1 adrenergic receptor antagonist terazosin based on relationships between
      plasma concentrations and blockade of intraurethral pressure (IUP) and mean
      arterial pressure (MAP) responses after single dosing and to determine cumulative
      effects after repeated dosing. To this end, the relationships between plasma
      concentrations and blockade effects of terazosin on phenylephrine (PE)-induced
      IUP and MAP were evaluated in conscious male beagle dogs after single (0.1, 0.3
      and 1 mg/kg) and repeated (0.3 and 1 mg/kg) daily oral dosing of terazosin.
      Blockade effects and plasma concentrations were evaluated at selected times for
      periods of < or = 24 hr. Terazosin produced dose-dependent antagonism of PE
      induced IUP and MAP responses. When IUP and MAP blockade effects were plotted
      against terazosin plasma concentration, direct relationships were observed that
      were well described by the sigmoidal maximal effect model and resulted in IUP and
      MAP IC50 values of 48.6 and 12.2 ng/ml, respectively. Repeated daily dosing
      resulted in little accumulation of terazosin in plasma and demonstrated
      consistent blockade responses over 7 days. MAP blockade was observed up to 23 hr
      after terazosin administration, whereas IUP blockade returned to control levels
      before 23 hr. Combined pharmacokinetic/pharmacodynamic analysis showed no
      selective antagonism of IUP by terazosin but may provide a useful way to show
      uroselectivity of novel agents.

PMID- 9262357
TI  - Dose-dependent pain-facilitatory and -inhibitory actions of neurotensin are
      revealed by SR 48692, a nonpeptide neurotensin antagonist: influence on the
      antinociceptive effect of morphine.
AB  - Neurotensin has bipolar (facilitatory and inhibitory) effects on pain modulation
      that may physiologically exist in homeostasis. Facilitation predominates at low
      (picomolar) doses of neurotensin injected into the rostroventral medial medulla
      (RVM), whereas higher doses (nanomolar) produce antinociception. SR 48692, a
      neurotensin receptor antagonist, discriminates between receptors mediating these
      responses. Consistent with its promotion of pain facilitation, the minimal
      antinociceptive responses to a 30-pmol dose of neurotensin microinjected into the
      RVM were markedly enhanced by prior injection of SR 48692 into the site (detected
      using the tail-flick test in awake rats). SR 48692 had a triphasic effect on the
      antinociception from a 10-nmol dose of neurotensin. Antinociception was
      attenuated by femtomolar doses, attenuation was reversed by low picomolar doses
      (corresponded to those blocking the pain-facilitatory effect of neurotensin) and
      the response was again blocked, but incompletely, by higher doses. The existence
      of multiple neurotensin receptor subtypes may explain these data.
      Physiologically, pain facilitation appears to be a prominent role for neurotensin
      because the microinjection of SR 48692 alone causes some antinociception.
      Furthermore, pain-facilitatory (i.e., antianalgesic) neurotensin mechanisms
      dominate in the pharmacology of opioids; the response to morphine administered
      either into the PAG or systemically was potentiated only by the RVM or systemic
      injection of SR 48692. On the other hand, reversal of the enhancement of
      antinociception occurred under certain circumstances with SR 48692, particularly
      after its systemic administration.

PMID- 9262358
TI  - Prediction of in vivo hepatic metabolic clearance of YM796 from in vitro data by
      use of human liver microsomes and recombinant P-450 isozymes.
AB  - The metabolic rate of (S)-(-)-2,8-dimethyl-3-methylene-1-oxa-8-azaspiro [4,5]
      decane-L-tartarate monohydrate (YM796), an antidementia agent, was determined by
      use of 12 different human liver microsomal samples. The metabolism of YM796 was
      shown to consist of three components; one high-affinity (Km1 = 1.67 microM), one
      low-affinity (Km2 = 654 microM) and a nonsaturable component. Good correlations
      were observed between the individual CYP3A4 content in 12 different human liver
      microsomal samples and kinetic parameters such as CL(int, all), the high-affinity
      component clearance (Vmax1/Km1) and the low-affinity component clearance
      (Vmax2/Km2). Anti-human CYP3A4/5 antibodies inhibited the metabolism of YM796 at
      1 microM by up to 75%. In addition, ketoconazole, an inhibitor of CYP3A4,
      inhibited YM796 metabolism by >90%. The metabolic clearance of YM796 in each of
      the 12 human liver microsomal samples was successfully predicted from the kinetic
      parameters obtained with the recombinant microsomes by taking into consideration
      the CYP3A4 content in each microsomal sample. Based on the CL(int, all) estimated
      from the in vitro experiments, the area under the plasma concentration-time curve
      after oral administration (AUC(oral)) of YM796 was also predicted by taking into
      account the hepatic blood flow rate (Qh), the unbound fraction of YM796 in human
      plasma (f(p)) and the fraction absorbed from the gut. In addition, AUC(oral) was
      determined in six healthy male volunteers. The predicted AUC(oral) was similar to
      the observed value in vivo, which suggests that the in vitro metabolism data
      obtained with human liver microsomes are useful for quantitatively predicting
      human liver metabolism in vivo and that recombinant microsomes are also available
      when the particular isozyme is almost completely responsible for the metabolism
      of the drug, the variation in P-450 content of human liver is known and the
      experimental conditions such as the amount of CYP reductase and cytochrome b5 are
      carefully optimized to mimic the activity found in native microsomes, as for
      YM796.

PMID- 9262359
TI  - WIN 35,428 and mazindol are mutually exclusive in binding to the cloned human
      dopamine transporter.
AB  - It has been suggested that cocaine and mazindol bind to separate sites on the
      dopamine transporter. In the present study, we address this issue by examining
      the inhibition by mazindol of the binding of [3H]WIN 35,428 ([3H]2beta
      carbomethyoxy-3beta-(4-fluorophenyl)-tropane), a phenyltropane analog of cocaine,
      and the inhibition by WIN 35,428 of [3H]mazindol binding to the cloned human
      dopamine transporter expressed in C6 glioma cells. The design involved the
      construction of inhibition curves at six widely different radioligand levels,
      enabling the distinction between the nonlinear hyperbolic competition (i.e.,
      negative allosteric) model and the competitive (i.e., mutually exclusive binding)
      model. Nonlinear computer curve-fitting analysis indicated no difference in the
      goodness of fit between the two models; the negative allosteric model indicated
      an extremely high allosteric constant of approximately > or = 100, which
      practically equates to the competitive model. The present results suggest that
      complex interactions reported between cocaine and mazindol in inhibiting dopamine
      transport are beyond the level of ligand recognition.

PMID- 9262360
TI  - Role of spinal gamma-aminobutyric acidA receptors in formalin-induced nociception
      in the rat.
AB  - This study investigated the role of gamma-aminobutyric acid (GABA) and GABA(A)
      receptors in the spinal cord in the expression of pain behaviors evoked by
      injection of formalin in concentrations ranging from 0.25 to 2.5% in the hindpaw
      of the rat. Two approaches were used. The first approach compared the effect of
      drug treatment to saline at each concentration of formalin. The second approach
      examined the effect of drug treatment on the concentration-response functions of
      formalin, i.e., its EC50. Intrathecal (i.t.) pretreatment with 0.03 to 0.3 microg
      of bicuculline, a GABA(A) receptor antagonist, dose-dependently increased the
      number of flinches and weighted pain scores in the interphase and phase 2, but
      did not alter responses in phase 1. In the interphase, the EC50 values of
      formalin for number of flinches or weighted pain score in bicuculline-pretreated
      rats were decreased to one-third or one-fourth, respectively, of their values in
      saline-pretreated rats. In phase 2, the EC50 values of formalin for number of
      flinches or weighted pain score in bicuculline-pretreated rats were similarly
      decreased to one-half of their value in saline-pretreated rats. These results
      suggest that formalin was a significantly more noxious stimulus in the presence
      of bicuculline. Pretreatment with the GABA(A) receptor agonists, muscimol (0.3
      microg) or isoguvacine (10 or 30 microg i.t.), significantly decreased the number
      of flinches in phase 1 and phase 2, but produced only a marginal decrease in the
      weighted pain score at the highest doses. These findings suggest that there is
      little tonic activation of GABA(A) receptors by GABA in the spinal cord before or
      immediately after the injection of formalin. However, approximately 10 min after
      the induction of injury by formalin, there is a release of GABA and activation of
      GABA(A) receptors in the spinal cord that 1) contributes to the period of
      quiescence between phase 1 and phase 2 and 2) coincidentally diminishes the
      magnitude of pain behaviors in phase 2, possibly by limiting the development of
      central sensitization in the spinal cord.

PMID- 9262361
TI  - Sex-related differences in morphine's antinociceptive activity: relationship to
      serum and brain morphine concentrations.
AB  - In earlier studies, it was shown that male rats were considerably more sensitive
      to the antinociceptive properties of morphine than females in several
      antinociceptive assays. The purpose of our studies was to examine whether these
      male-female differences might be due to differences in the blood and brain levels
      of morphine attained after its s.c. injection rather than to intrinsic
      differences in the central nervous system sensitivity to the drug. Our results
      confirmed that males were considerably more sensitive than females to the
      antinociceptive properties of morphine on the hot-plate test; the ED50 in males
      was approximately half that found in females. These sex differences were not
      unique to morphine because males were also more sensitive to the antinociceptive
      properties of the potent mu agonist, alfentanil. With respect to the
      pharmacokinetics of morphine, we found that there was a linear relationship in
      both males and females between the dose of morphine injected and the blood and
      brain levels achieved 60 min after the injection when the sex-linked differences
      in morphine-induced antinociception was greatest; no sex differences were found
      in the peak levels of morphine attained in blood or brain at any dose of
      morphine. Furthermore, there were no sex-linked differences in the elimination
      half-life of morphine from blood and, similarly, there were no differences in the
      disappearance of morphine from brain. On the basis of these data, it appears that
      the sex-related differences we have observed between males and females in the
      response to morphine's antinociceptive activity cannot be explained by
      differences in the pharmacokinetics of morphine. Rather, it appears that sex
      differences in morphine-induced antinociception are related to inherent
      differences in the sensitivity of the brain to morphine.

PMID- 9262362
TI  - Two affinity states of N-methyl-D-aspartate recognition sites: modulation by
      cations.
AB  - Previous studies have indicated that inorganic and organic cations can markedly
      affect parameters of the function of the N-methyl-D-aspartate receptor ionophore
      complex. As these effects may involve modulation of agonist binding, the purpose
      of our study was to investigate the stimulatory effect of mono- and divalent
      cations on binding properties of glutamate/N-methyl-D-aspartate recognition sites
      on the N-methyl-D-aspartate receptor complex, using [3H]CGP 39653 as the specific
      ligand for these sites. In well-washed membranes from rat brain, [3H]CGP 39653
      binding sites were present at two affinity states when assayed at 10 mM HEPES-KOH
      buffer. About 75% of these sites were in a low-affinity state (Kd = 210 +/- 30
      nM) although 25% were in a high-affinity state (Kd = 6.4 +/- 0.4 nM). Addition of
      mono- or divalent cations to the incubation medium stimulated [3H]CGP 39653
      binding, measured at a radioligand concentration of 4 nM. Maximal increases in
      binding were to approximately 230 and 400% of control, in the presence of mono-
      and divalent cations, respectively. Values of EC50 for stimulation were 5 to 7 mM
      for monovalent cations and 0.2 to 0.4 mM for divalent cations. At these
      concentrations, cations increased the Bmax for the high-affinity population of
      [3H]CGP 39653 sites and decreased the Bmax for low-affinity ones. These findings
      suggest that, like spermidine, inorganic cations stimulate binding by converting
      [3H]CGP 39653 binding sites from the low- to high-affinity state.

PMID- 9262363
TI  - Transport of quinolone antibacterial drugs by human P-glycoprotein expressed in a
      kidney epithelial cell line, LLC-PK1.
AB  - The purpose of this study was to characterize the transport mechanisms involved
      in the renal tubular secretion of quinolones. The contribution of P-glycoprotein
      to the transport of quinolones was elucidated using a kidney epithelial cell
      line, LLC-PK1, and its transfectant derivative cell line, LLC-GA5-COL150, which
      expresses human P-glycoprotein on the apical membrane. The transcellular
      transport of levofloxacin, a quinolone antibacterial drug, from the basolateral
      to apical side was increased in LLC-GA5-COL150 compared with that in LLC-PK1
      monolayers. The apparent Michaelis constant and maximum velocity values for the
      saturable transcellular transport of levofloxacin from the basolateral to apical
      side in LLC-GA5-COL150 monolayers were 3.0 mM and 45 nmol/mg protein per 15 min,
      respectively. The increased basolateral-to-apical transport in LLC-GA5-COL150
      monolayers was completely inhibited by cyclosporin A and quinidine to the level
      observed in LLC-PK1 monolayers. In addition, 3 mM levofloxacin inhibited the
      basolateral-to-apical transport of daunorubicin in LLC-GA5-COL150 monolayers. The
      basolateral-to-apical transport of another quinolone antibacterial drug, DU
      6859a, in LLC-GA5-COL150 monolayers greatly exceeded than that in LLC-PK1
      monolayers, and was inhibited by levofloxacin. These findings suggest that
      quinolone antibacterial drugs are transported by P-glycoprotein, and that P
      glycoprotein may contribute at least in part to the renal tubular secretion of
      quinolones.

PMID- 9262364
TI  - Differential effects of omega-conotoxin GVIA, nimodipine, calmidazolium and KN-62
      injected intrathecally on the antinociception induced by beta-endorphin, morphine
      and [D-Ala2,N-MePhe4,Gly-ol5]-enkephalin administered intracerebroventricularly
      in the mouse.
AB  - We previously reported that beta-endorphin and morphine administered
      supraspinally produce antinociception by activating different descending pain
      inhibitory systems. To determine the role of spinal calcium channels, calmodulin
      and calcium/calmodulin-dependent protein kinase II in the production of
      antinociception induced by morphine, [D-Ala2,N-MePhe4,Gly-ol5]-enkephalin (DAMGO)
      or beta-endorphin administered supraspinally, the effects of nimodipine (an L
      type calcium channel blocker), omega-conotoxin GVIA (an N-type voltage-dependent
      calcium channel blocker), calmidazolium (a calmodulin antagonist) or KN-62 (a
      calcium/calmodulin-dependent protein kinase II inhibitor) injected intrathecally
      (i.t.) on the antinociception induced by morphine, DAMGO or beta-endorphin
      administered intracerebroventricularly (i.c.v.) were examined in the present
      study. Antinociception was assessed by the mouse tail-flick test. The i.t.
      injection of nimodipine (from 0.024 to 2.4 pmol), omega-conotoxin GVIA (from
      0.0033 to 0.33 pmol), calmidazolium (from 0.0015 to 0.15 pmol) or KN-62 (from
      0.0014 to 0.14 pmol) alone did not affect the basal tail-flick latencies. The
      i.t. pretreatment of mice with nimodipine, omega-conotoxin GVIA, calmidazolium or
      KN-62 dose dependently attenuated the inhibition of the tail-flick response
      induced by beta-endorphin administered i.c.v. However, the inhibition of the tail
      flick response induced by morphine or DAMGO administered i.c.v. was not changed
      by i.t. pretreatment with nimodipine, omega-conotoxin GVIA, calmidazolium or KN
      62. The results suggest that spinally located L- and N-type calcium channels,
      calmodulin and calcium/calmodulin-dependent protein kinase II may be involved in
      the modulation of antinociception induced by beta-endorphin, but not morphine and
      DAMGO, administered supraspinally.

PMID- 9262365
TI  - Interaction between the forced swimming test and fluoxetine treatment on
      extracellular 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in the rat.
AB  - We used in vivo microdialysis to examine extracellular levels of 5
      hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the striatum
      and the lateral septum during the forced swimming test, (FST) a behavioral test
      conducted in rats that is commonly used to predict the effect of antidepressant
      drugs. The forced swimming test consisted of a 15-min pretest swim and a 5-min
      test swim 24 hr later. The antidepressant fluoxetine (20 mg/kg s.c.) or saline
      was administered 23.5, 5 and 1 hr before the test swim. In the striatum, the
      pretest swim increased 5-HT in both treatment groups. On the second day, the test
      swim had no effect on 5-HT in saline-treated rats but slightly decreased striatal
      5-HT in fluoxetine-treated rats. In the lateral septum, the pretest swim
      decreased 5-HT in both treatment groups. On the second day, the test swim had no
      effect on 5-HT in saline-treated rats but decreased lateral septum 5-HT in
      fluoxetine-treated rats. Ratings of behavior showed that fluoxetine treatment
      increased swimming behavior and decreased immobility during the test swim.
      Immobility was positively correlated and swimming was negatively correlated with
      changes in extracellular 5-HT in the lateral septum but not in the striatum.
      Therefore, fluoxetine treatment altered adaptation of the regional response of
      extracellular 5-HT ordinarily produced in the FST, reversing the 5-HT response to
      the initial swim in the striatum and restoring the response to the initial swim
      in the lateral septum.

PMID- 9262366
TI  - Inhibition of nitric oxide synthase enhances antinociception mediated by mu,
      delta and kappa opioid receptors in acute and prolonged pain in the rat spinal
      cord.
AB  - Our study was designed to determine involvement of nitric oxide (NO) in the
      antinociception mediated by mu, delta and kappa opioid receptors in acute and
      prolonged pain in the rat spinal cord. The effect of intrathecally (i.t.)
      injected NO synthase inhibitors and opioid receptor agonists was evaluated in
      acute pain using a tail-flick and a paw pressure tests, and in prolonged pain by
      quantification the pain-related behavior after peripheral formalin injection. It
      was found that the neuronal NO synthase inhibitor 7-nitroindazole (50-400
      microg), used in inactive doses, dose-dependently enhanced antinociception
      induced by morphine (0.5 microg) in the tail-flick and paw pressure. Moreover,
      coadministration of N(G)-nitro-L-arginine methyl ester (50 microg) another NO
      synthase inhibitor, with morphine (0.05-0.5 microg) as well as with specific
      agonists of mu ([D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin 0.1-2.5 ng) and delta ([D
      Pen(2,5)]enkephalin 0.02-0.5 microg) opioid receptors, enhanced dose-dependent
      antinociception in the tail-flick and paw pressure. Coadministration of N(G)
      nitro-L-arginine methyl ester with specific kappa opioid receptor agonist 3,4
      dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzenacetamid e (10-100
      microg), produced antinociception in the paw pressure only. Additionally, N(G)
      nitro-L-arginine methyl ester (100 microg) profoundly potentiated the
      antinociception induced by [D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin (0.5, 15 ng) and
      [D-Pen(2,5)]enkephalin (2, 10 microg) in the dose-related manner in the formalin
      test. N(G)-nitro-L-arginine methyl ester (100 microg) also enhanced the
      antinociception induced by 3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]
      benzenacetamid e (10-100 microg) but only at the last two time points of the
      second phase of the formalin test. These data show that inhibition of the spinal
      NO synthase potentiates the mu-, delta- and to a lesser extent, kappa-mediated
      spinal antinociception in both acute and prolonged pain.

PMID- 9262367
TI  - Efficiency of aerosolized nitric oxide donor drugs to achieve sustained pulmonary
      vasodilation.
AB  - Inhalation of nitric oxide (NO) causes selective pulmonary vasodilation, but
      demands continuous supply of the gaseous agent. We investigated the suitability
      of aerosolization of NO-donor drugs for achieving sustained reduction of
      pulmonary vascular tone. In buffer-perfused rabbit lungs, stable pulmonary
      hypertension was achieved by continuous infusion of the thromboxane-analogue
      U46619. The NO-donor drugs molsidomine, 3-morpholinosydnone-imine (SIN-1), sodium
      nitroprusside (SNP) and glyceryl-trinitrate reduced the pulmonary hypertension in
      a dose-dependent fashion, whether admixed to the perfusate or inhaled as alveolar
      accessible aerosol particles (aerosolization time 3-6 min), with an efficiency
      ranking of SNP > SIN-1 >> molsidomine and glyceryl-trinitrate. Notably, nearly
      identical dose-response curves were obtained when corresponding molar quantities
      of the most potent agents, SNP and SIN-1, were applied either via transbronchial
      or via intravascular routes, with respect to rapidity of onset, extent (pressure
      reduction to near baseline) and duration (>90 min) of vasorelaxation. Appearance
      of sydnonimines in the perfusate after aerosolization and reduction of SIN-1
      efficacy when nebulized in nonrecirculatingly perfused lungs demonstrated
      substantial entry of this prodrug into the vascular space after alveolar
      deposition. In contrast, undiminished vasodilatory efficacy of aerosolized SNP
      under conditions of non-recirculating perfusion suggested predominant efficacy
      via local NO release for this agent. We conclude that short aerosolization
      maneuvers of NO-donor drugs are suitable to achieve dose-dependent, extensive and
      sustained vasodilation in the pulmonary circulation, thus offering a new
      therapeutic approach in pulmonary hypertension.

PMID- 9262368
TI  - Pulmonary dendritic cell distribution and prevalence in guinea pig airways:
      effect of ovalbumin sensitization and challenge.
AB  - We characterized the localization and prevalence of dendritic cells (DC) in
      guinea pig airways before and after s.c. sensitization and aerosol challenge with
      ovalbumin (OVA). DC, eosinophils, macrophages, T cells and B cells in lung and
      trachea were identified and quantified in frozen sections using monoclonal
      antibodies and computer-assisted image analysis. Airway reactivity of conscious
      animals to inhaled methacholine was examined. In unsensitized animals, DC were
      localized primarily within the lamina propria of the trachea and bronchi, in the
      submucosa of the trachea and in the adventitia of the bronchi. In contrast to
      reported studies on rats, few DC were noted in the epithelium. After OVA
      challenge, sensitized animals demonstrated an early obstructive response and a
      late-phase response that was well developed by 18 hr. Challenge with OVA
      increased DC prevalence in the lamina propria and submucosa of the trachea and in
      the lamina propria and adventitia of the bronchi. There was widespread
      eosinophilia throughout the airways, but no changes in B cells or T cells were
      evident. Macrophages were increased in the epithelium of both OVA-treated and
      saline-treated animals. At 18 hr after challenge, sensitized guinea pigs but not
      saline-treated controls were hyperreactive to inhaled methacholine. Except for
      macrophages, none of these effects were observed after saline treatment. Our
      findings indicate that inflammation in the airways of OVA-sensitized guinea pigs
      involves infiltration of DC, which is seen at the time animals are hyperreactive
      to inhaled methacholine.

PMID- 9262369
TI  - Potency of truncated secretory leukoprotease inhibitor assessed in acute lung
      injury models in hamsters.
AB  - We evaluated the potency of truncated secretory leukoprotease inhibitor
      (truncated SLPI) in a human sputum elastase (HSE)-induced lung injury model and
      in a specific neutrophil-mediated acute lung injury model in hamsters.
      Intratracheal administration of HSE induced acute lung hemorrhage that could be
      measured by determination of the hemoglobin content in the bronchoalveolar lavage
      fluid. Intratracheal administration of truncated SLPI 1 hr before HSE
      administration inhibited acute lung hemorrhage in a dose-dependent manner (ED50 =
      46.8 microg/kg), as did i.v. injection of the inhibitor given 2 min before HSE
      administration (ED50 = 14.7 mg/kg). Intratracheal administration of endotoxin
      (lipopolysaccharide) induced pulmonary neutrophilia. Twenty-four hours after
      lipopolysaccharide administration, the addition of formyl-methionyl-leucyl
      phenylalanine resulted in a neutrophil-dependent acute lung injury that expressed
      an increase in hemoglobin content and in elastase-like activity in
      bronchoalveolar lavage fluids. In this model, lung injury was significantly
      attenuated by i.v. and intratracheal administration of truncated SLPI. These
      results suggest that truncated SLPI appears to be a good candidate inhibitor for
      the treatment of destructive lung diseases due to neutrophils.

PMID- 9262371
TI  - II. Localization and characterization of dopamine D4 binding sites in rat and
      human brain by use of the novel, D4 receptor-selective ligand [3H]NGD 94-1.
AB  - The dopamine D4 selective ligand, [H]NGD 94-1, was used in these studies to
      characterize binding sites in rat and human brain tissue by membrane binding and
      autoradiography techniques. Autoradiographic analysis of rat brain showed that
      specific [3H]NGD 94-1 binding was greatest in entorhinal cortex, lateral septal
      nucleus, hippocampus and the medial preoptic area of the hypothalamus. This
      nonstriatal distribution of [3H]NGD 94-1 binding was distinct from the
      autoradiographic distribution of dopamine D2 and D3 receptor subtypes. In
      homogenate preparations from rat brain regions, [3H]NGD 94-1 binding sites were
      low in density (<30.0 fmol/mg protein). The low density of D4 binding sites was
      corroborated by autoradiographic comparisons in which binding density for D4
      receptors as measured by [3H]NGD 94-1 was only 1/7 of D2 and 1/5 of D3 receptor
      densities, despite corrections for differing radioligand binding characteristics.
      Pharmacological evaluation showed high affinity at rat [3H]NGD 94-1 binding sites
      for compounds with known D4 receptor affinity and little displacement by
      compounds with affinity for dopamine D1/D2/D3 receptor subtypes. Specific, high
      affinity [3H]NGD 94-1 binding was also present in several human brain regions,
      including hippocampus, hypothalamus, dorsal medial thalamus, entorhinal cortex,
      prefrontal cortex and lateral septal nucleus. High-affinity [3H]NGD 94-1 binding
      was not present in any human striatal region examined. The pharmacological
      profile of [3H]NGD 94-1 binding sites in human brain was consistent with that
      previously demonstrated for cloned human D4 receptors expressed in mammalian
      cells. These findings suggest that specific, high-affinity [3H]NGD 94-1 binding
      exists in rat and human brain and that these sites reflect populations of
      dopamine D4 receptors with a distribution unique among dopamine receptor
      subtypes.

PMID- 9262370
TI  - I. NGD 94-1: identification of a novel, high-affinity antagonist at the human
      dopamine D4 receptor.
AB  - NGD 94-1 was evaluated for selectivity and in vitro functional activity at the
      recombinant human D4.2 receptor stably expressed in Chinese hamster ovary cells.
      NGD 94-1 showed high affinity for the cloned human D4.2 receptor (Ki = 3.6 +/-
      0.6 nM) and had greater than 600-fold selectivity for the D4.2 receptor subtype
      compared with a wide variety of monoamine or other neurotransmitter receptor or
      modulatory sites except for 5-HT1A and 5-HT3 receptors, in which NGD 94-1 was
      approximately 50- and 200-fold selective, respectively, for the D4.2 receptor. In
      measures of in vitro functional activity, NGD 94-1 showed an antagonist profile
      at the cloned human D4.2 receptor subtype. NGD 94-1 completely reversed the
      decrease in forskolin-stimulated cAMP levels produced by the dopamine receptor
      full agonist quinpirole. Furthermore, NGD 94-1 produced a complete reversal of
      GTPgamma35S binding induced by quinpirole, but was unable on its own to affect
      GTPgamma35S binding. These data suggest that NGD 94-1 functions as an antagonist
      rather than a full or partial agonist at the human D4.2 receptor. In addition,
      NGD 94-1 binding affinity at the D4.2 receptor subtype was unaffected by G
      protein activation by GTP, consistent with the binding affinity seen for other
      antagonists at the D4 receptor. The binding of tritiated NGD 94-1 was saturable
      and of high affinity at cloned human D4.2 receptors. Furthermore, the binding of
      [3H]NGD 94-1 to cloned human D4.2 receptors expressed in Chinese hamster ovary
      cells displayed a pharmacological profile similar to that observed with the
      nonselective dopamine receptor ligand [3H]YM 09151-2. Saturation and
      pharmacological analyses of [3H]NGD 94-1 binding at cloned human D4.2, D4.4 and
      D4.7 receptor variants showed no difference between the three variants. NGD 94-1
      is a novel, high-affinity, D4 receptor-selective antagonist. The clinical use of
      this subtype-specific compound should permit direct evaluation of the role of D4
      receptors in psychiatric disorders.

PMID- 9262372
TI  - Ethanol-mediated transplacental induction of CYP2E1 in fetal rat liver.
AB  - We examined the potential for the widely consumed xenobiotic ethanol to
      transplacentally induce fetal rat CYP2E1. Throughout gestation, rat dams were fed
      a liquid diet containing 5% ethanol or two separate control diets. At 2 days
      before term, the dams were killed, and maternal and embryonic tissues were
      collected. Immunoblot analysis of microsomes from fetal liver, placenta and
      maternal brain revealed a band that comigrated with adult liver CYP2E1. The
      identity of the immunoreactive protein in placenta, brain and fetal liver was
      substantiated as CYP2E1 through restriction enzyme digestion of a reverse
      transcription-polymerase chain reaction product. Quantification of immunoblots
      containing microsomes from maternal and fetal liver of ethanol-treated dams
      displayed a 1.4- and 2.4-fold increase in CYP2E1, respectively, compared with
      microsomes from pair-fed controls. Chlorzoxazone and low substrate concentrations
      of N-nitrosodimethylamine were used as metabolic probes for CYP2E1. The rate of
      chlorzoxazone metabolism by maternal hepatic microsomes from dams fed the 5%
      ethanol diet was 2.6-fold greater than that of controls. Conversely, a negligible
      increase was observed in the rate of metabolism by hepatic microsomes from
      ethanol-exposed fetuses compared with pair-fed animals. When N
      nitrosodimethylamine demethylation was examined, these same fetal samples
      exhibited greater rates of activity (1.5-fold) compared with microsomes from
      control animals. However, this increase was not as great as expected considering
      the 2.4-fold increase in CYP2E1 protein. Collectively, fetuses exposed to a 5%
      ethanol diet throughout gestation exhibited transplacental induction of an
      hepatic CYP2E1 that may possess different catalytic properties from the analogous
      adult enzyme.

PMID- 9262373
TI  - Alterations in thromboxane synthase and thromboxane A2 receptors in experimental
      alcoholic liver disease.
AB  - We have previously shown that hepatic thromboxane production is increased in
      experimental alcoholic liver disease. The present study was designed to
      investigate the cell type in liver responsible for increased thromboxane
      synthesis and the role of the thromboxane receptor system in the pathogenesis of
      liver injury. Male Wistar rats were divided into four groups and fed a liquid
      diet with dextrose or ethanol for 2, 4 and 8 weeks. Medium chain triglycerides or
      corn oil provided the dietary fatty acids. Kupffer cells, endothelial cells and
      hepatocytes were isolated from rats fed the different diets for 4 weeks. Liver
      histopathology, thromboxane synthase mRNA and protein, thromboxane levels and
      thromboxane receptor mRNA were evaluated in each group. In rats fed corn oil and
      ethanol, an increase in thromboxane synthase and liver levels of thromboxane
      metabolites were significantly higher than in the corn oil-dextrose-fed group and
      were correlated with the presence of pathological changes in the liver. Kupffer
      cells showed increased expression of thromboxane synthase. In rats fed medium
      chain triglycerides and ethanol, the levels of thromboxane synthase mRNA and
      protein were significantly lower than in the corn oil-ethanol-fed groups (P <
      .01) and liver injury was absent. However, the levels of thromboxane synthase
      mRNA, protein and thromboxane were significantly higher in the medium chain
      triglyceride-ethanol-fed rats than in the respective dextrose-fed controls. Among
      the different cell types, thromboxane A2-receptor mRNA levels were highest in the
      Kupffer cells in corn oil-ethanol-fed rats. The increase in thromboxane synthase
      in Kupffer cells together with an increase in thromboxane receptor levels
      suggests than thromboxanes may contribute to liver injury in ethanol-fed rats.

PMID- 9262374
TI  - Interaction of ethanol with inducible nitric oxide synthase messenger RNA and
      protein: direct effects on autacoids and endotoxin in vivo.
AB  - Inducible nitric oxide synthase (iNOS) mRNA is up-regulated in vivo by dibutyryl
      cAMP (db-cAMP), the purine-2y receptor agonist 2-methylthio-ATP and Escherichia
      coli endotoxin lipopolysaccharide (LPS). Ethanol and diethyldithiocarbamate
      inhibit LPS-stimulated iNOS mRNA. Their effects on db-cAMP- and 2-methylthio-ATP
      stimulated iNOS mRNA remain undefined. We examined the effect of ethanol (4.5
      g/kg intraperitoneal) and intratracheal diethyldithiocarbamate (5 mg/kg) on
      intratracheal LPS (0.6 mg/kg), db-cAMP (0.1 and 1 mg/kg) or 2-methylthio-ATP (5
      mg/kg)-stimulated rat alveolar macrophage (AM) iNOS mRNA and protein, reactive
      nitrogen intermediates nitrite and nitrate anion (RNI) and nuclear transcription
      factor-kappaB (NF-kappaB) in vivo. LPS and the autacoids increased iNOS mRNA and
      protein in rat AM and RNI in bronchoalveolar lavage fluid and in ex vivo
      incubates of AM compared with these parameters in control rats (n = 6-21/group).
      Only LPS up-regulated TNF-alpha mRNA and release of TNF-alpha in bronchoalveolar
      lavage fluid and AM. Ethanol inhibited LPS stimulation of the iNOS cascade at the
      level of transcription but inhibited only autacoid-stimulated iNOS protein and
      RNI. Diethyldithiocarbamate selectively inhibited the LPS-stimulated iNOS cascade
      at the level of transcription. Coadministration of ethanol and
      diethyldithiocarbamate inhibited LPS-stimulated iNOS mRNA, protein and RNI more
      than either inhibitor alone but did not differ from ethanol alone on autacoid
      stimulated iNOS protein or RNI. LPS increased and db-cAMP did not affect NF
      kappaB in AM. Ethanol inhibited LPS-stimulated NF-kappaB. Thus, two distinct
      pathways exist for induction of iNOS mRNA in rat AM in vivo: an NF-kappaB pathway
      for LPS and cytokines inhibitable by ethanol and diethyldithiocarbamate and an NF
      kappaB-independent pathway, refractory to inhibition by ethanol and
      diethyldithiocarbamate for db-cAMP and 2-mes-ATP. Finally, ethanol inhibits iNOS
      at the level of transcription and at the level of the enzyme.

PMID- 9262375
TI  - Substance P release in the rat periaqueductal gray and preoptic anterior
      hypothalamus after noxious cold stimulation: effect of selective mu and kappa
      opioid agonists.
AB  - Intracerebral microdialysis was used to measure changes in the extracellular
      level of substance P (SP) released from the periaqueductal gray (PAG) and the
      preoptic anterior hypothalamus (POAH) of freely moving Sprague-Dawley rats after
      noxious cold stimulation. Artificial cerebrospinal fluid was perfused into the
      dialysis probe in the PAG or POAH and samples were collected every 30 min for 4
      hr. SP-like immunoreactivity in the samples was measured by radioimmunoassay. In
      the PAG, SP base-line release was 0.43 +/- 0.08 fmol/fraction. SP release was
      increased to 1.3 +/- 0.4 fmol/fraction during the first collection period after
      noxious cold. Pretreatment with the selective mu opioid receptor agonist PL017
      (0.8-3.4 nmol) or the kappa opioid receptor agonist dynorphin A1-17 (4.6-9.2
      nmol), administered into the PAG by microinjection, produced dose-related
      inhibition of the cold-evoked SP release. Naloxone (10 mg/kg s.c.) administration
      10 min before these opioid agonists reduced the inhibition of SP release. In the
      POAH, SP base-line release was 0.45 +/- 0.06 fmol/fraction and noxious cold did
      not cause any significant change in SP release. Microdialysis of SP (271 fmol-271
      pmol/microl/min, for 30 min) into the PAG, but not the POAH, induced dose-related
      analgesia (35-68% MPA) in the cold-water tail-flick test. However, microdialysis
      of SP into the POAH or PAG failed to induce any significant change in body
      temperature. These data suggest that 1) SP released from the PAG acts as a
      neuromodulator to transmit nociceptive information; 2) opioid receptor agonists
      can suppress this information by inhibiting SP release; 3) SP evoked by noxious
      cold may have a role in triggering the antinociceptive function of the PAG; and
      4) SP does not appear to act as a neuromodulator for thermoregulatory responses
      in the POAH.

PMID- 9262376
TI  - Patients with delayed-onset sulfonamide hypersensitivity reactions have
      antibodies recognizing endoplasmic reticulum luminal proteins.
AB  - Sulfonamide antimicrobials cause a delayed-onset, hypersensitivity-type syndrome
      characterized by fever, skin rash and multiorgan toxicity occurring 7 to 14 days
      after initiation of therapy. The pathogenesis is believed to be immune-mediated.
      We investigated whether patients with delayed-onset sulfonamide hypersensitivity
      reactions had antibodies recognizing hapten-microsomal protein conjugates and/or
      native microsomal proteins. By immunoblotting using rat liver as a source of
      microsomal protein, 17 of 21 patients had antibodies recognizing one or more of
      three native endoplasmic reticulum proteins of 55 kDa (14 of 21 patients), 80 kDa
      (4 of 21 patients) or 96 kDa (3 of 21 patients) in size on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. No control subjects (n = 11) and only 1 of 18
      patients with adverse events not consistent with sulfonamide hypersensitivity
      reactions had antibodies against these microsomal proteins under the conditions
      used. Only 1 patient had antibodies that recognized the sulfonamide hapten,
      sulfamethoxazole. The 55-kDa protein was identified as protein disulfide
      isomerase. The 80-kDa protein was identified as grp78. The 96-kDa protein was not
      identified. Delayed-onset sulfonamide hypersensitivity reactions are therefore
      primarily associated with antibodies recognizing specific protein epitopes and
      not anti-drug antibodies.

PMID- 9262377
TI  - Nitric oxide and acetaminophen-mediated oxidative injury: modulation of
      interleukin-1-induced nitric oxide synthesis in cultured rat hepatocytes.
AB  - The role of endogenous hepatocyte synthesis of nitric oxide (NO) in states of
      oxidative stress is largely unknown. In a model of rat hepatocytes in primary
      culture, NO production was induced by exposure to interleukin-1beta (IL-1beta, 50
      ng/ml). Acetaminophen-mediated oxidative injury was analyzed in unstimulated and
      stimulated hepatocytes in the presence and absence of N-methyl-L-arginine, a
      substrate inhibitor of NO synthesis (100 microM). Inhibition of NO synthesis was
      associated with exacerbation of acetaminophen-mediated oxidative injury. This
      effect was independent of guanylyl cyclase and cytochrome P450 activity. In
      addition, oxidative stress was associated with augmentation of interleukin-1beta
      induced NO synthesis. Elevated NO synthesis occurred in parallel with increased
      inducible NO synthase (iNOS) enzyme activity and mass, steady-state levels of
      iNOS mRNA, increased transcription of the iNOS gene, and increased iNOS promoter
      activity. These effects were abrogated in the presence of antioxidants,
      suggesting that oxidative stress augments NO synthesis through a promoter
      specific transcriptional regulatory mechanism. Thus, in conditions where
      oxidative injury may be a component of the overall proinflammatory state,
      induction of iNOS with subsequent elaboration of NO and augmentation of NO
      production may serve as an hepatoprotective mechanism against oxidative injury.

PMID- 9262378
TI  - Comparative dose-dependence study of FK506 and cyclosporin A on the rate of
      axonal regeneration in the rat sciatic nerve.
AB  - The new immunosuppressant drug FK506 (Tacrolimus) increases the rate of nerve
      regeneration in vivo (Gold et al., 1994; Gold et al., 1995). In the present
      study, we have examined the dose-dependence of FK506's ability to enhance nerve
      regeneration. In the first set of experiments, rats received daily s.c.
      injections of FK506 (2 mg/kg, 5 mg/kg or 10 mg/kg) for 18 days after a sciatic
      nerve crush injury. Signs of functional recovery in the hind feet appeared
      earlier than in saline-treated control rats at all three FK506 dosage; recovery
      was maximally accelerated in the 5-mg/kg group. Light microscopy at 18 days after
      nerve crush revealed more regenerating myelinated fibers in FK506-treated rats
      than in controls; this was most apparent in the 5-mg/kg group. Morphometric
      analysis of axonal areas in the soleus nerve confirmed that axonal calibers were
      maximally increased in the 5-mg/kg group. In the second set of experiments, the
      rate of axonal regeneration was determined by radiolabeling the L5 dorsal root
      ganglion. Regeneration rate for sensory axons was maximally increased (by 34%) in
      the 5-mg/kg group. In contrast, cyclosporin A (10 or 50 mg/kg; dosages were
      selected on the basis of the 1/10 lower potency of cyclosporin A) did not
      significantly alter the rate of axonal regeneration. Cyclosporin A (50 mg/kg)
      also failed to increase functional recovery or axonal calibers in the soleus
      nerve. Because the two drugs share a common mechanism for producing
      immunosuppression (i.e., calcineurin inhibition), these results indicate that
      FK506's nerve regenerative property involves a distinct, calcineurin-independent
      mechanism.

PMID- 9262379
TI  - Evaluation of the antiinflammatory activity of a dual cyclooxygenase-2
      selective/5-lipoxygenase inhibitor, RWJ 63556, in a canine model of inflammation.
AB  - Sterile perforated polyethylene spheres (wiffle golf balls) were implanted s.c.
      in beagle dogs. A local inflammatory reaction was elicited within the spheres by
      injecting carrageenan. Changes in leukocyte count, prostaglandin E2, thromboxane
      B2 and leukotriene B4 levels were monitored in fluid samples collected over a 24
      hr period. Blood samples were also collected at various time points and analyzed
      for prostaglandin E2 and leukotriene B4 production after ex vivo calcium
      ionophore treatment. Effects of standard antiinflammatory agents (aspirin,
      indomethacin, dexamethasone, tenidap and zileuton) and newer cyclooxygenase-2
      (COX-2) selective agents (nimesulide, nabumetone and SC-58125) were determined
      after oral administration. Ex vivo inhibition of cyclooxygenase product synthesis
      (prostaglandin E2, thromboxane B2) in whole blood was used as an indicator of
      activity for the constitutive COX-1 isoform, although inhibition of the synthesis
      of these mediators in the chamber exudate during an inflammatory process is
      believed to represent COX-2 inhibition. Treatment effects on leukotriene B4
      production were also determined both ex vivo in whole blood and in the fluid. All
      of the compounds tested, except aspirin, inhibited leukocyte infiltration into
      the fluid exudate. Inhibitors that exert their effects on both isozymes of
      cyclooxygenase attenuate production of cyclooxygenase metabolites in both the
      inflammatory exudate and in peripheral blood ex vivo, although COX-2 selective
      inhibitors only demonstrated activity in the exudate. A 5-lipoxygenase inhibitor
      (zileuton), a corticosteroid (dexamethasone) and a dual COX-2 selective/5
      lipoxygenase inhibitor (RWJ 63556) had similar profiles in that they all
      inhibited cell infiltration and eicosanoid production in the fluid and also
      attenuated leukotriene B4 production in both the fluid and blood.

PMID- 9262381
TI  - Functional characterization of choroid plexus epithelial cells in primary
      culture.
AB  - The objective of this study was to develop and evaluate a primary culture system
      for choroid plexus epithelial cells as an in vitro model for studying organic
      cation transport. Cells were dispersed from choroid plexus of neonatal rats by
      enzymatic digestion and grew as differentiated monolayers when plated on solid or
      permeable support. Electron microscopy showed that cultured cells were
      morphologically similar to intact choroid plexus epithelium, having apical tight
      junctions between cells, numerous mitochondria, basal nuclei and apical
      microvilli and cilia. As previously demonstrated for intact choroid plexus,
      immunocytochemistry showed that Na+,K+-ATPase was localized to the apical
      membrane, and GLUT-1, the facilitative glucose transporter, was localized to the
      basolateral membrane of cultured cells. Apical transport of L-proline by cultured
      cells was mediated by a sodium-dependent, electrogenic process, as in whole
      tissue. 14C-Tetraethylammonium (TEA), a prototypic organic cation, was
      accumulated by isolated choroid plexus in a time-dependent manner; uptake was
      inhibited by tetrapentylammonium (TePA). In cultured cells, apical TEA transport
      was mediated by a saturable process coupled to cellular metabolism. Unlabeled TEA
      and other organic cations (TePA, N1-methylnicotinamide and mepiperphenidol)
      inhibited TEA transport; the organic anion, p-aminohippurate, had no effect.
      Finally, TePA-sensitive transport of 14C-TEA was stimulated after preloading the
      cells with unlabeled TEA. Based on the morphological, biochemical and functional
      properties of these cultured cells, we conclude that this primary culture system
      should be an excellent in vitro model for experimental characterization of
      choroid plexus function.

PMID- 9262380
TI  - Tissue specific toxicities of the anticancer drug 6-thioguanine is dependent on
      the Hprt status in transgenic mice.
AB  - 6-Thioguanine (6TG) a cytostatic antimetabolite is currently used to treat
      patients with cancer, in particular leukemias. However, one drawback of such use
      is the development of 6TG resistance. Hypoxanthine-guanine phosphoribosyl
      transferase (Hprt) plays a crucial role in the bioactivation of 6TG. Loss of Hprt
      has been associated with the resistance of leukemias to 6TG chemotherapy,
      however, nothing has been known about the effect of Hprt status on tissue
      specific toxicity of 6TG in vivo. We determined the effect of Hprt status on the
      tissue-specific toxicity of 6TG in vivo in transgenic Hprt-deficient mice. The
      approximate lethal dose for Hprt-deficient mice was 23-fold higher than for the
      wild-type. Serum biochemical analyses of 6TG-treated wild-type mice showed
      elevated serum enzyme levels characteristic of liver damage whereas the levels in
      Hprt-deficient 6TG-treated mice were within normal physiological limits.
      Histopathological examination of tissues from wild-type and from Hprt-deficient
      mice showed contrasting spectrums of microscopic lesions. Wild-type mice had loss
      of hematopoietic cells from bone marrow starting at the lowest dose of 25 mg/kg
      6TG whereas Hprt-deficient mice had normal bone marrow and spleen even at doses
      of 720 mg/kg 6TG. Wild-type mice also experienced severe loss of epithelial cells
      from the gastrointestinal tract starting at 50 mg/kg; however, the
      gastrointestinal tract of Hprt -/- mice remained unaffected. Wild-type livers
      revealed atrophy and necrosis at doses of 25 mg/kg 6TG although Hprt -/- livers
      displayed no effect until 507 mg/kg. In this study we show that Hprt-deficient
      mice had 6TG-resistant bone marrow and there are several other factors
      contributing to 6TG resistance in patients. Because variations among people exist
      in terms of their 6TG sensitivity, determining 6TG sensitivity of lymphocytes
      prior to 6TG chemotherapy and restricting treatment to 6TG-sensitive patients may
      improve the efficacy.

PMID- 9262382
TI  - Distinct regulation of two hydroxysteroid sulfotransferases, ST2A1 and ST2A2, by
      growth hormone: a unique type of growth hormone regulation in rats.
AB  - In the present study, changes in the mRNAs of two major forms of hydroxysteroid
      sulfotransferases (STs), ST2A1 and ST2A2, have been determined in different
      growth hormone (GH) states. Hepatic ST2A1 mRNA was detected in both sexes of
      mature Sprague-Dawley rats. The level was 5 times higher in the females than in
      the males. ST2A1 mRNA was undetectable in GH-deficient animals, such as
      hypophysectomized rats and spontaneous dwarf rats. Continuous infusion of GH
      (mimicking the female secretory pattern) increased hepatic levels of ST2A1 mRNA
      in both GH-deficient animals. ST2A2 mRNA was detected only in the livers of
      mature female rats and in both sexes of GH-deficient animals. Intermittent
      injection of GH (mimicking male secretory pattern) strongly suppressed hepatic
      levels of ST2A2 mRNA in both GH-deficient animals. These results indicate that
      pituitary GH independently regulates both ST2A1 and ST2A2 at the pretranslational
      levels. These differences in GH responses between ST2A1 and ST2A2 are in good
      agreement with their female-dominant and female-specific modes of expression in
      normal rats. Furthermore, the present study demonstrates a unique response of
      ST2A2 to the secretory pattern of GH among the drug-metabolizing enzymes in rat
      livers, in which ST2A2 mRNA levels are suppressed by the male secretory pattern
      but not by the female secretory pattern of GH.

PMID- 9262384
TI  - Flawed understanding of the scientific process.

PMID- 9262383
TI  - An okadaic acid-sensitive pathway involved in the phenobarbital-mediated
      induction of CYP2B gene expression in primary rat hepatocyte cultures.
AB  - We have previously demonstrated that specific activation of a cAMP-dependent
      protein kinase A (PKA) pathway resulted in complete repression of phenobarbital
      (PB)-inducible CYP gene expression in primary rat hepatocyte cultures. In the
      current investigation, we examined the role of protein phosphatase pathways as
      potential co-regulators of this repressive response. Primary rat hepatocytes were
      treated with increasing concentrations (0.1-25 nM) of okadaic acid, a potent
      inhibitor of serine/threonine-specific protein phosphatases PP1 and PP2A. PB
      induction responses were assessed by use of specific hybridization probes to
      CYP2B1 and CYP2B2 mRNAs. Okadaic acid completely inhibited the PB induction
      process in a concentration-dependent manner (IC50, approximately 1.5-2 nM).
      Similar repression was obtained with low concentrations of other highly specific
      phosphatase inhibitors, tautomycin and calyculin A. In contrast, exposure of
      hepatocytes to 1-nor-okadaone or okadaol, negative analogs of okadaic acid
      largely devoid of phosphatase inhibitory activity, was without effect on the PB
      induction process. At similar concentrations, okadaic acid produced only
      comparatively weak modulation of the beta-naphthoflavone-inducible CYP1A1 gene
      expression pathway. In additional experiments, hepatocytes were treated with
      suboptimal concentrations of PKA activators together with phosphatase inhibitors.
      Okadaic acid markedly potentiated the repressive effects of dibutyryl-cAMP on the
      PB induction process. Together, these results indicate that both PKA and protein
      phosphatase (PP1 and/or PP2A) pathways exert potent and complementary control of
      the intracellular processes modulating the signaling of PB in cultured primary
      rat hepatocytes.

PMID- 9262385
TI  - Fight over Italian research policy threatens chance for reform.

PMID- 9262387
TI  - After Dolly, meet Gene, the cloned calf.

PMID- 9262386
TI  - US to tighten protection of medical data.

PMID- 9262388
TI  - 'Neutral' mechanism sought to fund environmental research.

PMID- 9262389
TI  - Make marijuana research easier, panel urges NIH.

PMID- 9262390
TI  - Head of French leukaemia inquiry quits after partisan remarks.

PMID- 9262391
TI  - Evolutionary biology. Even-toed fingerprints on whale ancestry.

PMID- 9262392
TI  - Adenosine receptors. Knockouts anxious for new therapy.

PMID- 9262393
TI  - Immunotherapy. Fusion induces tumour rejection.

PMID- 9262394
TI  - LDL-receptor structure. Calcium cages, acid baths and recycling receptors.

PMID- 9262395
TI  - Stochastic resonance at the single-cell level.

PMID- 9262396
TI  - Sequence-specific RNA binding by bicoid.

PMID- 9262397
TI  - Fossils, genes and the evolution of animal limbs.
AB  - The morphological and functional evolution of appendages has played a crucial
      role in the adaptive radiation of tetrapods, arthropods and winged insects. The
      origin and diversification of fins, wings and other structures, long a focus of
      palaeontology, can now be approached through developmental genetics.
      Modifications of appendage number and architecture in each phylum are correlated
      with regulatory changes in specific patterning genes. Although their respective
      evolutionary histories are unique, vertebrate, insect and other animal appendages
      are organized by a similar genetic regulatory system that may have been
      established in a common ancestor.

PMID- 9262398
TI  - Conspecific sperm precedence in Drosophila.
AB  - Traits that influence the interactions between males and females can evolve very
      rapidly through sexual selection or sexually antagonistic coevolution. Rapid
      change in the fertilization systems of independent populations can give rise to
      reproductive incompatibilities between populations, and may contribute to
      speciation. Here I provide evidence for cryptic reproductive divergence among
      three sibling species of Drosophila that leads to a form of postmating isolation.
      When a female mates with both a conspecific and a heterospecific male, the
      conspecific sperm fertilize the vast majority of the eggs, regardless of the
      order of the matings. Heterospecific sperm fertilize fewer eggs after these
      double matings than after single matings. Experiments using spermless males show
      that the seminal fluid of the conspecific male is largely responsible for this
      conspecific sperm precedence. Moreover, when two males of the same species mate
      sequentially with a female from a different species, a highly variable pattern of
      sperm precedence replaces the second-male sperm precedence that is consistently
      found within species. These results indicate that females mediate sperm
      competition, and that second-male sperm precedence is not an automatic
      consequence of the mechanics of sperm storage.

PMID- 9262399
TI  - Molecular evidence from retroposons that whales form a clade within even-toed
      ungulates.
AB  - The origin of whales and their transition from terrestrial life to a fully
      aquatic existence has been studied in depth. Palaeontological, morphological and
      molecular studies suggest that the order Cetacea (whales, dolphins and porpoises)
      is more closely related to the order Artiodactyla (even-toed ungulates, including
      cows, camels and pigs) than to other ungulate orders. The traditional view that
      the order Artiodactyla is monophyletic has been challenged by molecular analyses
      of variations in mitochondrial and nuclear DNA. We have characterized two
      families of short interspersed elements (SINEs) that were present exclusively in
      the genomes of whales, ruminants and hippopotamuses, but not in those of camels
      and pigs. We made an extensive survey of retropositional events that might have
      occurred during the divergence of whales and even-toed ungulates. We have
      characterized nine retropositional events of a SINE unit, each of which provides
      phylogenetic resolution of the relationships among whales, ruminants,
      hippopotamuses and pigs. Our data provide evidence that whales, ruminants and
      hippopotamuses form a monophyletic group.

PMID- 9262400
TI  - Formation of olfactory memories mediated by nitric oxide.
AB  - Sheep learn to recognize the odours of their lambs within two hours of giving
      birth, and this learning involves synaptic changes within the olfactory bulb.
      Specifically, mitral cells become increasingly responsive to the learned odour,
      which stimulates release of both glutamate and GABA (gamma-aminobutyric acid)
      neurotransmitters from the reciprocal synapses between the excitatory mitral
      cells and inhibitory granule cells. Nitric oxide (NO) has been implicated in
      synaptic plasticity in other regions of the brain as a result of its modulation
      of cyclic GMP levels. Here we investigate the possible role of NO in olfactory
      learning. We find that the neuronal enzyme nitric oxide synthase (nNOS) is
      expressed in both mitral and granule cells, whereas the guanylyl cyclase subunits
      that are required for NO stimulation of cGMP formation are expressed only in
      mitral cells. Immediately after birth, glutamate levels rise, inducing formation
      of NO and cGMP, which potentiate glutamate release at the mitral-to-granule cell
      synapses. Inhibition of nNOS or guanylyl cyclase activity prevents both the
      potentiation of glutamate release and formation of the olfactory memory. The
      effects of nNOS inhibition can be reversed by infusion of NO into the olfactory
      bulb. Once memory has formed, however, inhibition of nNOS or guanylyl cyclase
      activity cannot impair either its recall or the neurochemical release evoked by
      the learned lamb odour. Nitric oxide therefore seems to act as a retrograde
      and/or intracellular messenger, being released from both mitral and granule cells
      to potentiate glutamate release from mitral cells by modulating cGMP
      concentrations. We propose that the resulting changes in the functional circuitry
      of the olfactory bulb underlie the formation of olfactory memories.

PMID- 9262401
TI  - Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine
      A2a receptor.
AB  - Adenosine is released from metabolically active cells by facilitated diffusion,
      and is generated extracellularly by degradation of released ATP. It is a potent
      biological mediator that modulates the activity of numerous cell types, including
      various neuronal populations, platelets, neutrophils and mast cells, and smooth
      muscle cells in bronchi and vasculature. Most of these effects help to protect
      cells and tissues during stress conditions such as ischaemia. Adenosine mediates
      its effects through four receptor subtypes: the A1, A2a, A2b and A3 receptors.
      The A2a receptor (A2aR) is abundant in basal ganglia, vasculature and platelets,
      and stimulates adenylyl cyclase. It is a major target of caffeine, the most
      widely used psychoactive drug. Here we investigate the role of the A2a receptor
      by disrupting the gene in mice. We found that A2aR-knockout (A2aR-/-) mice were
      viable and bred normally. Their exploratory activity was reduced, whereas
      caffeine, which normally stimulates exploratory behaviour, became a depressant of
      exploratory activity. Knockout animals scored higher in anxiety tests, and male
      mice were much more aggressive towards intruders. The response of A2aR-/- mice to
      acute pain stimuli was slower. Blood pressure and heart rate were increased, as
      well as platelet aggregation. The specific A2a agonist CGS 21680 lost its
      biological activity in all systems tested.

PMID- 9262402
TI  - Altered pain perception and inflammatory response in mice lacking prostacyclin
      receptor.
AB  - Prostanoids are a group of bioactive lipids working as local mediators and
      include D, E, F and I types of prostaglandins (PGs) and thromboxanes.
      Prostacyclin (PGI2) acts on platelets and blood vessels to inhibit platelet
      aggregation and to cause vasodilatation, and is thought to be important for
      vascular homeostasis. Aspirin-like drugs, including indomethacin, which inhibit
      prostanoid biosynthesis, suppress fever, inflammatory swelling and pain, and
      interfere with female reproduction, suggesting that prostanoids are involved in
      these processes, although it is not clear which prostanoid is the endogenous
      mediator of a particular process. Prostanoids act on seven-transmembrane-domain
      receptors which are selective for each type. Here we disrupt the gene for the
      prostacyclin receptor in mice by using homologous recombination. The receptor
      deficient mice are viable, reproductive and normotensive. However, their
      susceptibility to thrombosis is increased, and their inflammatory and pain
      responses are reduced to the levels observed in indomethacin-treated wild-type
      mice. Our results establish that prostacyclin is an antithrombotic agent in vivo
      and provide evidence for its role as a mediator of inflammation and pain.

PMID- 9262403
TI  - Crustacean appendage evolution associated with changes in Hox gene expression.
AB  - Homeotic (Hox) genes specify the differential identity of segments along the body
      axis of insects. Changes in the segmental organization of arthropod bodies may
      therefore be driven by changes in the function of Hox genes, but so far this has
      been difficult to demonstrate. We show here that changes in the expression
      pattern of the Hox genes Ubx and AbdA in different crustaceans correlate well
      with the modification of their anterior thoracic limbs into feeding appendages
      (maxillipeds). Our observations provide direct evidence that major morphological
      changes in arthropod body plans are associated with changes in Hox gene
      regulation. They suggest that homeotic changes may play a role in the normal
      process of adaptive evolutionary change.

PMID- 9262404
TI  - Recruitment of functional GABA(A) receptors to postsynaptic domains by insulin.
AB  - Modification of synaptic strength in the mammalian central nervous system (CNS)
      occurs at both pre- and postsynaptic sites. However, because postsynaptic
      receptors are likely to be saturated by released transmitter, an increase in the
      number of active postsynaptic receptors may be a more efficient way of
      strengthening synaptic efficacy. But there has been no evidence for a rapid
      recruitment of neurotransmitter receptors to the postsynaptic membrane in the
      CNS. Here we report that insulin causes the type A gamma-aminobutyric acid
      (GABA[A]) receptor, the principal receptor that mediates synaptic inhibition in
      the CNS, to translocate rapidly from the intracellular compartment to the plasma
      membrane in transfected HEK 293 cells, and that this relocation requires the
      beta2 subunit of the GABA(A) receptor. In CNS neurons, insulin increases the
      expression of GABA(A) receptors on the postsynaptic and dendritic membranes. We
      found that insulin increases the number of functional postsynaptic GABA(A)
      receptors, thereby increasing the amplitude of the GABA(A)-receptor-mediated
      miniature inhibitory postsynaptic currents (mIPSCs) without altering their time
      course. These results provide evidence for a rapid recruitment of functional
      receptors to the postsynaptic plasma membrane, suggesting a fundamental mechanism
      for the generation of synaptic plasticity.

PMID- 9262405
TI  - Molecular basis of familial hypercholesterolaemia from structure of LDL receptor
      module.
AB  - The low-density lipoprotein receptor (LDLR) is responsible for the uptake of
      cholesterol-containing lipoprotein particles into cells. The amino-terminal
      region of LDLR, which consists of seven tandemly repeated, approximately 40-amino
      acid, cysteine-rich modules (LDL-A modules), mediates binding to lipoproteins.
      LDL-A modules are biologically ubiquitous domains, found in over 100 proteins in
      the sequence database. The structure of ligand-binding repeat 5 (LR5) of the
      LDLR, determined to 1.7 A resolution by X-ray crystallography and presented here,
      contains a calcium ion coordinated by acidic residues that lie at the carboxy
      terminal end of the domain and are conserved among LDL-A modules. Naturally
      occurring point mutations found in patients with the disease familial
      hypercholesterolaemia alter residues that directly coordinate Ca2+ or that serve
      as scaffolding residues of LR5.

PMID- 9262407
TI  - Attention, awareness, and the triangular circuit.
AB  - It is proposed that attention to an object requires the simultaneous activity of
      three brain regions that are interconnected by a triangular circuit. The regions
      are the cortical site of attentional expression, the thalamic enhancement
      structure, and the prefrontal area of control. It is also proposed that awareness
      of an object requires the additional component of attention directed to a
      representation of the self. The expression of attention to a self-representation
      may involve activations of cortical sites corresponding to the body landscape
      and/or verbal-based memories of autobiographical episodes. As in the case of
      attention to objects, attention to the self is presumed to involve a triangular
      circuit. The proposed triangular circuit of attention is shown to be generally
      consistent with current knowledge of brain structures and with data from a broad
      range of experiments concerned with the functions of neurons in these structures.

PMID- 9262406
TI  - Crystal structure of a small G protein in complex with the GTPase-activating
      protein rhoGAP.
AB  - Small G proteins transduce signals from plasma-membrane receptors to control a
      wide range of cellular functions. These proteins are clustered into distinct
      families but all act as molecular switches, active in their GTP-bound form but
      inactive when GDP-bound. The Rho family of G proteins, which includes Cdc42Hs,
      activate effectors involved in the regulation of cytoskeleton formation, cell
      proliferation and the JNK signalling pathway. G proteins generally have a low
      intrinsic GTPase hydrolytic activity but there are family-specific groups of
      GTPase-activating proteins (GAPs) that enhance the rate of GTP hydrolysis by up
      to 10(5) times. We report here the crystal structure of Cdc42Hs, with the non
      hydrolysable GTP analogue GMPPNP, in complex with the GAP domain of p50rhoGAP at
      2.7A resolution. In the complex Cdc42Hs interacts, mainly through its switch I
      and II regions, with a shallow pocket on rhoGAP which is lined with conserved
      residues. Arg 85 of rhoGAP interacts with the P-loop of Cdc42Hs, but from
      biochemical data and by analogy with the G-protein subunit G(i alpha1), we
      propose that it adopts a different conformation during the catalytic cycle which
      enables it to stabilize the transition state of the GTP-hydrolysis reaction.

PMID- 9262408
TI  - Constraints on awareness, attention, processing, and memory: some recent
      investigations with ignored speech.
AB  - We discuss potential benefits of research in which attention is directed toward
      or away from a spoken channel and measures of the allocation of attention are
      used. This type of research is relevant to at least two basic, still-unresolved
      issues in cognitive psychology: (a) the extent to which unattended information is
      processed and (b) the extent to which unattended information that is processed
      can later be remembered. Four recent studies of this type that address these
      questions in various ways (Cowan, Lichty, & Grove, 1990; Wood & Cowan, 1995a,b;
      Wood, Stadler & Cowan, in press) are reviewed as illustrations. We conclude from
      these studies that (a) unattended information appears to be partially processed
      automatically, though attention enhances the processing considerably, and (b) the
      unattended information that is processed may not be retrievable in direct or many
      indirect memory tasks, though it remains possible that there is an automatically
      stored memory trace (e.g., one that could produce semantic priming).

PMID- 9262409
TI  - Attention and semantic priming: a review of prime task effects.
AB  - The single-word semantic priming paradigm is a tool for investigating how and
      when word meaning (semantic) activation occurs during visual word recognition.
      The prime task effect refers to the elimination of the typically robust semantic
      priming effect by a nonsemantic prime task (e.g., subjects search the prime word
      for a letter). The purpose of this paper is to provide a tutorial review of the
      literature examining the prime task effect. Understanding the nature of this
      effect has implications for delineating how selective attention modulates
      evidence for semantic activation during word reading. These implications are
      outlined. Additionally, speculations for how these issues of selective attention
      relate to awareness are offered.

PMID- 9262410
TI  - Parallels between perception without attention and perception without awareness.
AB  - Do studies of perception without awareness and studies of perception without
      attention address a similar underlying concept of awareness? To answer this
      question, we compared qualitative differences in performance across variations in
      stimulus quality (i.e., short vs. long prime-mask stimulus onset asynchrony) with
      qualitative differences in performance across variations in the direction of
      attention (i.e., focused vs. divided). The qualitative differences were based on
      three different phenomena: Stroop priming, false recognition, and exclusion
      failure. In all cases, variations in stimulus quality and variations in the
      direction of attention led to parallel findings. These results suggest that
      perception with and without awareness and perception with and without attention
      are equivalent ways of describing the same underlying process distinction.

PMID- 9262411
TI  - What is it like to be a patient with apperceptive agnosia?
AB  - Neuropsychological deficits have been widely used to elucidate normal cognitive
      functioning. Can patients with such deficits also be used to understand conscious
      visual experience? In this paper, we ask what it would be like to be a patient
      with apperceptive agnosia (a deficit in object recognition). Philosophical
      analyses of such questions have suggested that subjectively experiencing what
      another person experiences would be impossible. Although such roadblocks into the
      conscious experience of others exist, the experimental study of both patients and
      neurologically normal subjects can be used to understand visual processing
      mechanisms. In order to understand the visual processes damaged in apperceptive
      agnosia, we first review this syndrome and present a case study of one such
      patient, patient J.W. We then review several theoretical accounts of apperceptive
      agnosia, and we conclude that studies of the patients themselves may not allow us
      to discriminate between the various explanations of the syndrome. To test these
      accounts, we have simulated apperceptive agnosia in neurologically normal
      subjects. The implications of our results for understanding both apperceptive
      agnosia and normal visual processing are discussed.

PMID- 9262412
TI  - Brain mechanisms of cognitive skills.
AB  - This article examines the anatomy and circuitry of skills that, like reading,
      calculating, recognizing, or remembering, are common abilities of humans. While
      the anatomical areas active are unique to each skill there are features common to
      all tasks. For example, all skills produce activation of a small number of widely
      separated neural areas that appear necessary to perform the task. These neural
      areas relate to internal codes that may not be observed by any external behavior
      nor be reportable by the performer. There is considerable plasticity to the
      performance of skills. Task components can be given priority through attention,
      which serves to increase activation of the relevant brain areas. Attention can
      also cause reactivation of sensory areas driven by input, but usually only after
      a delay. The threshold for activation for any area may be temporarily reduced by
      prior activation (priming or practice). Skill components requiring attention tend
      to cause interference resulting in the dual tasks effects and unified focus of
      attention described in many cognitive studies. Practice may change the size or
      number of brain areas involved and alter the pathways used by the skill. By
      combining cognitive and anatomical analyses, a more general picture of the nature
      of skill emerges.

PMID- 9262413
TI  - Inhibitory tagging of locations in the blind field of hemianopic patients.
AB  - This study evaluated the potential contribution of extrageniculate visual
      pathways to oculomotor orienting reflexes in hemianopic patients. It tested
      whether extrageniculate pathways mediate inhibition of return (IOR)-a phenomenon
      characterized by slowed target detections at recently stimulated locations
      (Posner & Cohen, 1984). Because hemianopic subjects cannot overtly respond to
      stimuli presented within their hemianopic field, we utilized a spatial cueing
      paradigm that capitalized on the fact that IOR operates in spatiotopic
      coordinates. Subjects moved their eyes so that a cue and a target presented at
      the same spatial location were imaged successively onto blind and seeing portions
      of their retinas. One hemianopic patient showed a similar IOR effect from cues
      presented within both the seeing and the hemianopic fields. With a second
      hemianopic patient, only presentations of the cue to the subject's seeing field
      produced IOR. The explanation for this discrepancy is not evident. These
      observations highlight both the potential value and the pitfalls inherent in
      using "blindsight" as a window into human consciousness.

PMID- 9262414
TI  - Negative priming, attention, and discriminating the present from the past.
AB  - Priming effects have been used widely as a tool to study attentional processes.
      However, inferences regarding attention depend on how priming effects are
      interpreted. In the case of negative priming, an activation-based framework for
      interpreting priming suggests that attention inhibits the representation of prime
      distractors and that this inhibition is measured in performance to subsequent
      probes. Data summarized in this article point out that negative priming does not
      depend on selection of one of two primes and that attentional influences during
      retrieval play an important role in determining negative priming. Also, two
      experiments are described that demonstrate a correlation between priming effects
      and knowledge of the relation between primes and probes. We suggest that negative
      priming is not determined directly by a process of ignoring, but instead occurs
      because a repeated probe is less temporally distinct when ignored as a prime than
      when attended.

PMID- 9262415
TI  - Facilitatory or inhibitory nontarget effects in the location-cuing paradigm.
AB  - The effect of nontargets on the identification of targets in the location-cuing
      paradigm was investigated in order to determine whether observers consistently
      allocate their attention to a validly cued location and whether the effect of
      nontargets is to facilitate or to inhibit performance. In four experiments, the
      effects of a single matching nontarget or a single nonmatching nontarget were
      compared. In each experiment, it was shown that observers consistently allocate
      their attention to a cued location when a precue appears and that performance is
      inhibited more by nonmatching nontargets in the display than it is facilitated by
      matching nontargets.

PMID- 9262416
TI  - Understanding diverse effects of visual attention with the VAP-filters metaphor.
AB  - The Variable and Permeable Filters (VAP-Filters) metaphor is presented with an
      explanation of its advantages over other popular metaphors in accounting for
      attention effects in many different research paradigms. Research from
      laboratories of the author and others are discussed briefly and shown to result
      in diverse facilitatory and inhibitory attention effects on visual perception.
      All of these effects are consistent with the VAP-Filters metaphor.

PMID- 9262417
TI  - Some essential differences between consciousness and attention, perception, and
      working memory.
AB  - When "divided attention" methods were discovered in the 1950s their implications
      for conscious experience were not widely appreciated. Yet when people process
      competing streams of sensory input they show both selective processes and clear
      contrasts between conscious and unconscious events. This paper suggests that the
      term "attention" may be best applied to the selection and maintenance of
      conscious contents and distinguished from consciousness itself. This is
      consistent with common usage. The operational criteria for selective attention,
      defined in this way, are entirely different from those used to assess
      consciousness. To illustrate the scientific usefulness of the distinction it is
      applied to Posner's (1994) brain model of visual attention. It seems that
      features that are often attributed to attention-like limited capacity-may more
      accurately be viewed as properties of consciousness.

PMID- 9262418
TI  - The phenomenology of attention. 2. Brightness and contrast.
AB  - The effect of attention on perceived brightness and contrast was investigated in
      eight experiments. Attention was manipulated by engaging observers in an
      attention-demanding concurrent task (letter detection) or by directing attention
      to a location with a peripheral cue. In all of the dual-task manipulations,
      attention reduced the variability of responses. However, attention did not affect
      the brightness of stimuli, nor did it affect the amount of simultaneous
      brightness contrast. Results with peripheral location cues were similar; however,
      the effect of attention in these experiments could be attributed to nonperceptual
      factors. The metaphorical "spotlight" of attention reduces observers' uncertainty
      about the brightness of a stimulus, but it does not "illuminate" in terms of
      brightness or contrast.

PMID- 9262420
TI  - Limited capacity of any realizable perceptual system is a sufficient reason for
      attentive behavior.

PMID- 9262419
TI  - Successive approximations to an adequate model of attention.
AB  - Everybody knows the phenomena summarized with the term attention: concentration,
      focalization, limitation, selection, and intensification (see, e.g., James,
      1890/1950). The explanation of these phenomena is, however, a different matter.
      Problems easily arise with regard to what has to be explained and with regard to
      the style of explanation. A problem of the first kind is the "methodology of 'bad
      focus'": the explanation starts with and is fixated on an intuitively striking
      but nonessential behavioral feature or cognitive achievement. A problem of the
      second kind is a "virtus dormitiva" explanation: the explanation starts with
      emphasizing one aspect of the observed phenomena, the emphasized aspect receives
      an interesting and suggestive name, and that name with its connotations is used
      as a concept in the explanation. At the start of contemporary, behavior-based,
      information processing psychology, a virtus dormitiva explanation infiltrated the
      functional accounts of the phenomena of attention; the empirical observation that
      people show performance limitations was translated into the theoretical concept
      of a communication channel with a limited capacity. That limited capacity notion
      became the core concept in what can be called the standard theory of attention.
      This standard theory of attention faced severe difficulties in explaining the
      guidance of attention by the information processor's goals and intentions.
      Subsequent modifications, concerned with removing these difficulties, revealed
      that selection, guided by goals and intentions, is the essential behavioral
      feature and that the observed performance limitations are a result of this
      selection. So, the limited capacity theorizing was not only plagued by a virtus
      dormitiva explanation, it also suffered from the methodology of bad focus.

PMID- 9262421
TI  - Eye movements and attention.

PMID- 9262422
TI  - Specifying the relations between automaticity and consciousness: a theoretical
      note.
AB  - The relations between automatic processing and (the absence of) consciousness are
      discussed in this paper. It is argued that automatic processing should not be
      identified with the absence of consciousness. The organism has access to
      representations resulting from automatic processing, but these representations,
      in contrast to the representations resulting from nonautomatic processing, are
      not propositional. Therefore monitoring of the process, the defining feature of
      nonautomatic processing, is not possible.

PMID- 9262423
TI  - Invited editorial on "Airway thermal volume in humans and its relation to body
      size".

PMID- 9262424
TI  - Pathogenesis of nitrofen-induced congenital diaphragmatic hernia in fetal rats.
AB  - Congenital diaphragmatic hernia (CDH) is a developmental anomaly characterized by
      the malformation of the diaphragm and impaired lung development. In the present
      study, we tested several hypotheses regarding the pathogenesis of CDH, including
      those suggesting that the primary defect is due to abnormal 1) lung development,
      2) phrenic nerve formation, 3) developmental processes underlying diaphragmatic
      myotube formation, 4) pleuroperitoneal canal closure, or 5) formation of the
      primordial diaphragm within the pleuroperitoneal fold. The 2,4-dichloro-phenyl-p
      nitrophenyl ether (nitrofen)-induced CDH rat model was used for this study. The
      following parameters were compared between normal and herniated fetal rats at
      various stages of development: 1) weight, protein, and DNA content of lungs; 2)
      phrenic nerve diameter, axonal number, and motoneuron distribution; 3) formation
      of the phrenic nerve intramuscular branching pattern and diaphragmatic myotube
      formation; and 4) formation of the precursor of the diaphragmatic musculature,
      the pleuroperitoneal fold. We demonstrated that previously proposed theories
      regarding the primary role of the lung, phrenic nerve, myotube formation, and the
      closure of pleuroperitoneal canal in the pathogenesis of CDH are incorrect.
      Rather, the primary defect associated with CDH, at least in the nitrofen rat
      model, occurs at the earliest stage of diaphragm development, the formation of
      the pleuroperitoneal fold.

PMID- 9262425
TI  - Expression of nitric oxide synthase isoforms in normal ventilatory and limb
      muscles.
AB  - Nitric oxide (NO), an important messenger molecule with widespread actions, is
      synthesized by NO synthases (NOS). In this study, we investigated the correlation
      between fiber type and NOS activity among ventilatory and limb muscles of various
      species. We also assessed the presence of the three NOS isoforms in normal
      skeletal muscles and how various NOS inhibitors influence muscle NOS activity.
      NOS activity was detected in various muscles; however, NOS activity in rabbits
      and rats varied significantly among different muscles. Immunoblotting of muscle
      samples indicated the presence of both the neuronal NOS and the endothelial NOS
      isoforms but not the cytokine-inducible NOS isoform. However, these isoforms were
      expressed to different degrees in various muscles. Although the neuronal NOS
      isoform was detectable in the canine diaphragm, very weak expression was detected
      in rabbit, rat, and mouse diaphragms. The endothelial NOS isoform was detected in
      the rat and mouse diaphragms but not in the canine and rabbit diaphragms. We also
      found that NG-nitro-L-arginine methyl ester, 7-nitroindazole, and S
      methylisothiourea were stronger inhibitors of muscle NOS activity than was
      aminoguanidine. These results indicate the presence of different degrees of
      constitutive NOS expression in normal ventilatory and limb muscles of various
      species. Our data also indicate that muscle NOS activity is not determined by
      fiber type distribution but by other not yet identified factors. The functional
      significance of this expression remains to be assessed.

PMID- 9262427
TI  - Posthemorrhagic antipyresis: what stage of fever genesis is affected?
AB  - It has been shown that hemorrhage leads to a decreased thermal responsiveness to
      lipopolysaccharide (LPS). The aim of this study was to clarify what stage of
      fever genesis [production of endogenous pyrogens such as interleukin-1 (IL-1),
      increase of the prostaglandin E2 (PGE2) concentration in brain tissue, activation
      of cold-defense effectors] is deficient in posthemorrhagic antipyresis. In adult
      rabbits, we evaluated the effect of acute hemorrhage (15 ml/kg) on the rectal
      temperature (Tre) responses to LPS from Salmonella typhi (200 ng/kg iv), ethanol
      purified preparation of homologous IL-1 (1 ml from 3.5 x 10(7) cells, 1.5 ml/kg
      iv), and PGE2 (1 microg, intracisternal injection). The effect of hemorrhage on
      Tre was also studied in afebrile rabbits, both at thermoneutrality (23 degrees C)
      and during ramp cooling (to 7 degrees C). The hemorrhage strongly attenuated the
      biphasic LPS-induced fever (a Tre rise of 0.4 +/- 0.1 instead of 1.2 +/- 0.2
      degrees C at the time of the second peak), the monophasic Tre response to IL-1
      (by approximately 0.5 degrees C for over 1-5 h postinjection), and the PGE2
      induced hyperthermia (0.4 +/- 0.1 vs. 0.9 +/- 0.1 degrees C, maxima). In afebrile
      animals, the hemorrhage neither affected Tre at thermoneutrality nor changed the
      Tre response to cold exposure. The data suggest that neither insufficiency of
      cold-defense effectors nor lack of endogenous mediators of fever (IL-1, PGE2) can
      be the only or even the major cause of posthemorrhagic antipyresis. We speculate
      that fever genesis is altered at a stage occurring after the intrabrain PGE2
      level is increased but before thermoeffectors are activated.

PMID- 9262429
TI  - Effects of transient intrathoracic pressure changes (hiccups) on systemic
      arterial pressure.
AB  - The purpose of the study was to determine the effect of transient changes in
      intrathoracic pressure on systemic arterial pressure by utilizing hiccups as a
      tool. Values of systolic and diastolic pressures before, during, and after
      hiccups were determined in 10 intubated preterm infants. Early-systolic hiccups
      decreased systolic blood pressure significantly (P < 0.05) compared with control
      (39.38 +/- 2.72 vs. 46.46 +/- 3.41 mmHg) and posthiccups values, whereas no
      significant change in systolic blood pressure occurred during late-systolic
      hiccups. Diastolic pressure immediately after the hiccups remained unchanged
      during both early- and late-systolic hiccups. In contrast, diastolic pressure
      decreased significantly (P < 0.05) when hiccups occurred during diastole (both
      early and late). Systolic pressures of the succeeding cardiac cycle remained
      unchanged after early-diastolic hiccups, whereas they decreased after late
      diastolic hiccups. These results indicate that transient decreases in
      intrathoracic pressure reduce systemic arterial pressure primarily through an
      increase in the volume of the thoracic aorta. A reduction in stroke volume
      appears to contribute to the reduction in systolic pressure.

PMID- 9262426
TI  - Acutely administered melatonin reduces oxidative damage in lung and brain induced
      by hyperbaric oxygen.
AB  - Hyperbaric oxygen exposure rapidly induces lipid peroxidation and cellular damage
      in a variety of organs. In this study, we demonstrate that the exposure of rats
      to 4 atmospheres of 100% oxygen for 90 min is associated with increased levels of
      lipid peroxidation products [malonaldehyde (MDA) and 4-hydroxyalkenals (4-HDA)]
      and with changes in the activities of two antioxidative enzymes [glutathione
      peroxidase (GPX) and glutathione reductase (GR)], as well as in the glutathione
      status in the lungs and in the brain. Products of lipid peroxidation increased
      after hyperbaric hyperoxia, both GPX and GR activities were decreased, and levels
      of total glutathione (reduced+oxidized) and glutathione disulfide (oxidized
      glutathione) increased in both lung and brain areas (cerebral cortex,
      hippocampus, hypothalamus, striatum, and cerebellum) but not in liver. When
      animals were injected with melatonin (10 mg/kg) immediately before the 90-min
      hyperbaric oxygen exposure, all measurements of oxidative damage were prevented
      and were similar to those in untreated control animals. Melatonin's actions may
      be related to a variety of mechanisms, some of which remain to be identified,
      including its ability to directly scavenge free radicals and its induction of
      antioxidative enzymes via specific melatonin receptors.

PMID- 9262428
TI  - Interaction between airway edema and lung inflation on responsiveness of
      individual airways in vivo.
AB  - Interaction between airway edema and lung inflation on responsiveness of
      individual airways in vivo. J. Appl. Physiol. 83(2): 366-370, 1997.-Inflammatory
      changes and airway wall thickening are suggested to cause increased airway
      responsiveness in patients with asthma. In five sheep, the dose-response
      relationships of individual airways were measured at different lung volumes to
      methacholine (MCh) before and after wall thickening caused by the inflammatory
      mediator bradykinin via the bronchial artery. At 4 cmH2O transpulmonary pressure
      (Ptp), 5 microg/ml MCh constricted the airways to a maximum of 18 +/- 3%. At 30
      cmH2O Ptp, MCh resulted in less constriction (to 31 +/- 5%). Bradykinin increased
      airway wall area at 4 and 30 cmH2O Ptp (159 +/- 6 and 152 +/- 4%, respectively; P
      < 0.0001). At 4 cmH2O Ptp, bradykinin decreased airway luminal area (13 +/- 2%; P
      < 0.01), and the dose-response curve was significantly lower (P = 0.02). At 30
      cmH2O, postbradykinin, the maximal airway narrowing was not significantly
      different (26 +/- 5%; P = 0.76). Bradykinin produced substantial airway wall
      thickening and slight potentiation of the MCh-induced airway constriction at low
      lung volume. At high lung volume, bradykinin increased wall thickness but had no
      effect on the MCh-induced airway constriction. We conclude that inflammatory
      fluid leakage in the airways cannot be a primary cause of airway
      hyperresponsiveness.

PMID- 9262431
TI  - Vasomotor instability preceding tilt-induced syncope: does respiration play a
      role?
AB  - This study aimed to determine whether alterations in cardiovascular dynamics
      before syncope are related to changes in spontaneous respiration. Fifty-two
      healthy subjects underwent continuous heart rate (HR), arterial blood pressure
      (BP), and respiratory measurements during 10-min periods of spontaneous and paced
      breathing (0.25 Hz) in the supine and 60 degrees head-up tilt positions. Data
      were evaluated by power spectrum and transfer function analyses. During tilt, 27
      subjects developed syncope or presyncope and 25 remained asymptomatic. Subjects
      with tilt-induced syncope had significantly greater increases in low-frequency
      (0.04-0. 15 Hz) systolic BP, diastolic BP, and HR power during tilt than the
      asymptomatic subjects (P </= 0.01). This difference was present during
      spontaneous but not paced breathing. However, average tidal volume, respiratory
      rate, minute ventilation, proportion of breaths below 0.15 Hz, and low-frequency
      respiratory power during tilt did not differ between syncopal and nonsyncopal
      subjects. Transfer magnitudes between low-frequency respiration and BP, and
      between BP and interbeat interval, were also similar between groups. Thus
      vasomotor instability before syncope is not related to alterations in respiration
      or the cardiovagal baroreflex but may reflect oscillating central sympathetic
      outflow to the vasculature.

PMID- 9262430
TI  - Fluid regulatory hormone response to exercise after coca-induced body fluid
      shifts.
AB  - To determine the effect of coca chewing on heart rate (HR), mean arterial blood
      pressure (MAP), and plasma volume and their relationship with the hormones
      regulating cardiovascular and body fluid homeostasis, 16 male volunteers were
      examined at rest and during 1 h of cycle exercise at approximately 75% of their
      peak oxygen uptake in two trials separated by 1 mo. One trial was performed after
      the subjects chewed a sugar-free chewing gum (Coca- trial), whereas the other was
      done after the subjects chewed 15 g of coca leaves (Coca+), with the order of the
      Coca- and Coca+ trials being randomized. Blood samples were taken at rest, before
      (R1) and after 1-h chewing (R2), and during the 5th, 15th, 30th, and 60th min of
      exercise. They were analyzed for hematocrit, hemoglobin concentration, red blood
      cell count, plasma proteins, and for the fluid regulatory hormones, including
      plasma catecholamines [norepinephrine (NE) and epinephrine], renin, arginine
      vasopressin, and the atrial natriuretic peptide (ANP). During the control trial
      (Coca-), from R1 to R2, there was no significant change in hematologic, hormonal,
      and cardiovascular status except for a small increase in plasma NE. In contrast,
      it can be calculated that coca chewing at rest induced a significant
      hemoconcentration (-3.8 +/- 1. 3% in blood and -7.0 +/- 0.7% in plasma volume),
      increased NE and MAP, and reduced plasma ANP. Chewing coca before exercise
      reduced the body fluid shifts but enhanced HR response during exercise. These
      effects were not accompanied by changes in NE, epinephrine, renin, and arginine
      vasopressin plasma levels. In contrast, plasma ANP response to exercise was lower
      during the Coca+ trial, suggesting that central cardiac filling was reduced by
      coca use. It is likely that the reduction in body fluid volumes is a major
      contributing factor to the higher HR at any given time of exercise after coca
      chewing.

PMID- 9262432
TI  - Cerebellar modulation of cough motor pattern in cats.
AB  - Cerebellar modulation of cough motor pattern in cats. J. Appl. Physiol. 83(2):
      391-397, 1997.-The cerebellum modulates respiratory muscle activity in part via
      its influence on the central respiratory pattern generator. Because coughing
      requires well-coordinated respiratory muscle activity, studies were conducted to
      determine whether the cerebellum influences the centrally generated cough motor
      pattern. Integrated phrenic and lumbar efferent neurograms (PN and LN,
      respectively) were monitored in decerebrated, paralyzed, and ventilated cats.
      Mechanical probing of the intrathoracic trachea was used to evoke fictive coughs;
      i.e., large increases in PN and LN amplitudes. Cerebellectomy resulted in a
      decrease in the number of coughs per trial (cough frequency) and LN peak
      amplitudes without any consistent change in PN peak amplitudes. Cerebellar nuclei
      [the rostral interposed nucleus (INr) and the rostral fastigial nucleus (FNr)]
      known to be involved in respiratory control were ablated to determine their
      potential role in the cough response. Control (eupneic) respiratory frequency was
      not affected by cerebellectomy or INr/FNr lesions. Cough frequency was depressed
      by lesion of the INr but not by ablation of the FNr. No significant changes in PN
      and LN amplitudes were observed after lesion of either the INr or FNr. These
      results suggest that the cerebellum, specifically the INr, is involved in
      modulation of the frequency of centrally generated coughing.

PMID- 9262433
TI  - Mechanical properties of rabbit latissimus dorsi muscle after stretch and/or
      electrical stimulation.
AB  - The work loop technique was used to measure the mechanical performance in situ of
      the latissimus dorsi (LD) muscles of rabbits maintained under fentanyl
      anesthesia. After 3 wk of incrementally applied stretch the LD muscles were 36%
      heavier, but absolute power output (195 mW/muscle) was not significantly changed
      relative to that of external control muscle (206 mW). In contrast, continuous 10
      Hz electrical stimulation reduced power output per kilogram of muscle >75% after
      3 or 6 wk and muscle mass by 32% after 6 wk. When combined, stretch and 10-Hz
      electrical stimulation preserved or increased the mass of the treated muscles but
      failed to prevent an 80% loss in maximum muscle power. However, this combined
      treatment increased fatigue resistance to a greater degree than electrical
      stimulation alone. These stretched/stimulated muscles, therefore, are more
      suitable for cardiomyoplasty. Nonetheless, further work will be necessary to find
      an ideal training program for this surgical procedure.

PMID- 9262434
TI  - Transcapillary escape rate of albumin in humans during exercise-induced
      hypervolemia.
AB  - To test the hypotheses that plasma volume (PV) expansion 24 h after intense
      exercise is associated with reduced transcapillary escape rate of albumin
      (TERalb) and that local changes in transcapillary forces in the previously active
      tissues favor retention of protein in the vascular space, we measured PV, TERalb,
      plasma colloid osmotic pressure (COPp), interstitial fluid hydrostatic pressure
      (Pi), and colloid osmotic pressure in leg muscle and skin and capillary
      filtration coefficient (CFC) in the arm and leg in seven men and women before and
      24 h after intense upright cycle ergometer exercise. Exercise expanded PV by 6.4%
      at 24 h (43.9 +/- 0.8 to 46.8 +/- 1.2 ml/kg, P < 0.05) and decreased total
      protein concentration (6.5 +/- 0.1 to 6.3 +/- 0.1 g/dl, P < 0.05) and COPp (26.1
      +/- 0.8 to 24.3 +/- 0.9 mmHg, P < 0.05), although plasma albumin concentration
      was unchanged. TERalb tended to decline (8.4 +/- 0.5 to 6.5 +/- 0.7%/h, P = 0.11)
      and was correlated with the increase in PV (r = -0.69, P < 0.05). CFC increased
      in the leg (3.2 +/- 0.2 to 4.3 +/- 0.5 microl . 100 g-1 . min-1 . mmHg-1, P < 0.
      05), and Pi showed a trend to increase in the leg muscle (2.8 +/- 0. 7 to 3.8 +/-
      0.3 mmHg, P = 0.08). These data demonstrate that TERalb is associated with PV
      regulation and that local transcapillary forces in the leg muscle may favor
      retention of albumin in the vascular space after exercise.

PMID- 9262435
TI  - Effects of renal denervation on cardiovascular and renal responses to ACE
      inhibition in conscious lambs.
AB  - Effects of renal denervation on cardiovascular and renal responses to ACE
      inhibition in conscious lambs. J. Appl. Physiol. 83(2): 414-419, 1997.
      Cardiovascular and renal effects of either the angiotensin-converting enzyme
      inhibitor captopril or vehicle were measured in chronically instrumented lambs in
      the presence (intact; n = 6) and absence of renal sympathetic nerves (denervated;
      n = 5) to determine whether there was an interaction between the renin
      angiotensin system and renal sympathetic nerves early in life. Captopril caused a
      similar decrease in mean arterial pressure (P < 0. 001) in intact and denervated
      lambs, predominantly through a decrease in diastolic pressure. Heart rate was
      increased from 177 +/- 34 to 213 +/- 22 (SD) beats/min during captopril compared
      with vehicle infusion in intact lambs. In denervated lambs, basal heart rates
      were elevated to 218 +/- 33 beats/min; there was no further increase in heart
      rate during captopril compared with vehicle infusion. Captopril infusion caused a
      decrease in renal vascular resistance but only in the absence of renal nerves.
      These findings provide evidence to suggest that early in life there is an
      interaction between renal sympathetic nerves and the renin-angiotensin system in
      regulating renal hemodynamics and the baroreflex control of the heart.

PMID- 9262437
TI  - More tetanic contractions are required for activating glucose transport maximally
      in trained muscle.
AB  - Exercise training increases contraction-stimulated maximal glucose transport and
      muscle glycogen level in skeletal muscle. However, there is a possibility that
      more muscle contractions are required to maximally activate glucose transport in
      trained than in untrained muscle, because increased glycogen level after training
      may inhibit glucose transport. Therefore, the purpose of this study was to
      investigate the relationship between the increase in glucose transport and the
      number of tetanic contractions in trained and untrained muscle. Male rats swam 2
      h/day for 15 days. In untrained epitrochlearis muscle, resting glycogen was 26.6
      micromol glucose/g muscle. Ten, 10-s-long tetani at a rate of 1 contraction/min
      decreased glycogen level to 15.4 micromol glucose/g muscle and maximally
      increased 2-deoxy-D-glucose (2-DG) transport. Training increased contraction
      stimulated maximal 2-DG transport (+71%; P < 0.01), GLUT-4 protein content (+78%;
      P < 0.01), and resting glycogen level (to 39.3 micromol glucose/g muscle; P <
      0.01) on the next day after the training ended, although this training effect
      might be due, at least in part, to last bout of exercise. In trained muscle, 20
      tetani were necessary to maximally activate glucose transport. Twenty tetani
      decreased muscle glycogen to a lower level than 10 tetani (18.9 vs. 24.0 micromol
      glucose/g muscle; P < 0.01). Contraction-stimulated 2-DG transport was negatively
      correlated with postcontraction muscle glycogen level in trained (r = -0.60; P <
      0.01) and untrained muscle (r = -0.57; P < 0.01).

PMID- 9262436
TI  - Focal central chemoreceptor sensitivity in the RTN studied with a CO2 diffusion
      pipette in vivo.
AB  - We describe and use a CO2 diffusion pipette to produce a quickly reversible focal
      acidosis in the retrotrapezoid nucleus region of the rat brain stem. No tissue
      injection is made. Instead, artificial cerebrospinal fluid (aCSF) equilibrated
      with CO2 circulates within the micropipette, providing a source for continued CO2
      diffusion into the tissue from the pipette tip. Tissue pH electrodes show the
      acidosis is limited to 500 micron from the tip. In controls (aCSF equilibrated
      with air), 1-min pipette perfusions increased tissue pH slightly and decreased
      phrenic nerve amplitude. In moderate- and high-CO2 groups (aCSF equilibrated with
      50 or 100% CO2), 1-min perfusions significantly decreased tissue pH and increased
      phrenic nerve amplitude in a dose-dependent manner. The responses developed and
      reversed within minutes. Compared with our prior use of medullary acetazolamide
      injections to produce a focal acidosis, in this approach the acidosis 1) arises
      and reverses quickly and 2) its intensity can be varied. This allows study of
      sensitivity and mechanism. We conclude from this initial experiment that
      retrotrapezoid nucleus region chemoreceptors operate within the normal
      physiological range of CO2-induced tissue pH changes.

PMID- 9262438
TI  - Contractile responsiveness of coronary arteries from exercise-trained rats.
AB  - The purpose of this study was to determine whether exercise training alters
      vasomotor reactivity of rat coronary arteries. In vitro isometric microvessel
      techniques were used to evaluate vasomotor properties of proximal left anterior
      artery rings (1 ring per animal) from exercise-trained rats (ET; n = 10)
      subjected to a 12-wk treadmill training protocol (32 m/min, 15% incline, 1 h/day,
      5 days/wk) and control rats (C; n = 6) restricted to cage activity. No
      differences in passive length-tension characteristics or internal diameter (158
      +/- 9 and 166 +/- 9 micron) were observed between vessels of C and ET rats.
      Concentration-response curves to K+ (5-100 mM), prostaglandin F2alpha (10(-8)-10(
      4) M), and norepinephrine (10(-8)-10(-4)) were unaltered (P > 0.05) in coronary
      rings from ET rats compared with C rats; however, lower values of the
      concentration producing 50% of the maximal contractile response in rings from ET
      rats (P = 0.05) suggest that contractile sensitivity to norepinephrine was
      enhanced. Vasorelaxation responses to sodium nitroprusside (10(-9)-10(-4) M) and
      adenosine (10(-9)-10(-4) M) were not different (P > 0.05) between vessels of C
      and ET rats. However, relaxation responses to the endothelium-dependent
      vasodilator acetylcholine (ACh; 10(-10)-10(-4) M) were significantly blunted (P <
      0.001) in coronary rings from ET animals; maximal ACh relaxation averaged 90 +/-
      5 and 46 +/- 12%, respectively, in vessels of C and ET groups. In additional
      experiments, two coronary rings (proximal and distal) were isolated from each C
      (n = 7) and ET (n = 7) animal. Proximal coronary artery rings from ET animals
      demonstrated decreased relaxation responses to ACh; however, ACh-mediated
      relaxation of distal coronary rings was not different between C and ET groups. NG
      monomethyl-L-arginine (inhibitor of nitric oxide synthase) blocked ACh relaxation
      of all rings. L-Arginine (substrate for nitric oxide synthase) did not improve
      the blunted ACh relaxation in proximal coronary artery rings from ET rats. These
      studies suggest that exercise-training selectively decreases endothelium
      dependent (ACh) but not endothelium-independent (sodium nitroprusside) relaxation
      responses of rat proximal coronary arteries; endothelium-dependent relaxation of
      distal coronary arteries is unaltered by training.

PMID- 9262440
TI  - Effect of hypoxia on respiratory system impedance in dogs.
AB  - The effects of hypoxia on lung and airway mechanics remain controversial,
      possibly because of the confounding effects of competing reflexes caused by
      systemic hypoxemia. We compared the effects of systemic hypoxemia with those of
      unilateral alveolar hypoxia (with systemic normoxemia) on unilateral respiratory
      system impedance (Z) in intact, anesthetized dogs. Independent lung ventilation
      was obtained with a Kottmeier endobronchial tube. Individual left and right
      respiratory system Z was measured during sinusoidal forcing with 45 ml of volume
      at frequencies of 0.2-2.1 Hz during control [100% inspired O2 fraction (FIO2)],
      systemic hypoxemia (10% FIO2), and unilateral alveolar hypoxia (0% FIO2 to left
      lung, 100% FIO2 to right lung). During systemic hypoxemia, there was a mean Z
      magnitude increase of 18%. This change was entirely attributable to a decrease in
      the imaginary component of Z; there was no change in the real component of Z.
      Administration of atropine (0.2 mg/kg) did not block the increase in Z with
      systemic hypoxemia. In contrast, there was no change in Z in the lung subjected
      to unilateral alveolar hypoxia. We conclude that alveolar hypoxia has no direct
      effect on lung mechanical properties in intact dogs. In contrast, systemic
      hypoxemia does increase lung impedance, apparently through a noncholinergic
      mechanism.

PMID- 9262439
TI  - Contractile apparatus and sarcoplasmic reticulum function: effects of fatigue,
      recovery, and elevated Ca2+.
AB  - This investigation tested the notion that fatiguing stimulation induces intrinsic
      changes in the contractile apparatus and sarcoplasmic reticulum (SR) and that
      these changes are initiated by elevated intracellular Ca2+ concentration
      ([Ca2+]i). Immediately after stimulation of frog semitendinosus muscle,
      contractile apparatus and SR function were measured. Despite a large decline in
      tetanic force (Po), maximal Ca2+-activated force (Fmax) of the contractile
      apparatus was not significantly altered. However, Ca2+ sensitivity was increased.
      In conjunction, the rate constant of Ca2+ uptake by the SR was diminished, and
      the caffeine sensitivity of Ca2+ release was decreased. During recovery, Po,
      contractile apparatus, and SR function each returned to near-initial levels.
      Exposure of skinned fibers to 0.5 microM free Ca2+ for 5 min depressed both Fmax
      and Ca2+ sensitivity of the contractile apparatus. In addition, caffeine
      sensitivity of Ca2+ release was diminished. Results suggest that fatigue induces
      intrinsic alterations in contractile apparatus and SR function. Changes in
      contractile apparatus function do not appear to be mediated by increased [Ca2+]i.
      However, a portion of the change in SR Ca2+ release seems to be due to elevated
      [Ca2+]i.

PMID- 9262441
TI  - Chronic beta-blockade increases skeletal muscle beta-adrenergic-receptor density
      and enhances contractile force.
AB  - The effects of a chronic 14-day administration of a selective beta2-adrenergic
      receptor antagonist (ICI-118551) on skeletal muscle were evaluated in female
      Sprague-Dawley rats. Chronic ICI-118551 treatment did not modify muscle mass,
      oxidative potential, or protein concentration of the medial gastrocnemius muscle,
      suggesting that maintenance of these skeletal muscle characteristics is not
      dependent on beta2-adrenergic-receptor stimulation. However, the drug treatment
      increased beta-adrenergic-receptor density of the lateral gastrocnemius (42%) and
      caused an increase in specific (g/g) isometric in situ contractile forces of the
      medial gastrocnemius [twitch, 56%; tetanic (200 Hz), 28%]. The elevated
      contractile forces observed after a chronic treatment with ICI-118551 were
      completely abolished when the beta2-adrenergic antagonist was also administered
      acutely before measurement of contractile forces, suggesting that this response
      is beta2-adrenergic-receptor dependent. Possible mechanisms for the increased
      forces were studied. Caffeine administration potentiated twitch forces but had
      little effect on tetanic force in control animals. Administration of dibutyryl
      adenosine 3',5'-cyclic monophosphate in control animals also resulted in small
      increases of twitch force but did not modify tetanic forces. We conclude that
      increases in beta-adrenergic-receptor density and the stimulation of the
      receptors by endogenous catecholamines appear to be responsible for increased
      contractile forces but that the mechanism remains to be demonstrated.

PMID- 9262442
TI  - Ventilatory stability to transient CO2 disturbances in hyperoxia and normoxia in
      awake humans.
AB  - Modarreszadeh and Bruce (J. Appl. Physiol. 76: 2765-2775, 1994) proposed that
      continuous random disturbances in arterial PCO2 are more likely to elicit
      ventilatory oscillation patterns that mimic periodic breathing in normoxia than
      in hyperoxia. To test this hypothesis experimentally, in nine awake humans we
      applied pseudorandom binary inspired CO2 fraction stimulation in normoxia and
      hyperoxia to derive the closed-loop and open-loop ventilatory responses to a
      brief CO2 disturbance in terms of impulse responses and transfer functions. The
      closed-loop impulse response has a significantly higher peak value [0.143 +/-
      0.071 vs. 0.079 +/- 0.034 (SD) l . min-1 . 0.01 l CO2-1, P = 0.014] and a
      significantly shorter 50% response duration (42.7 +/- 13.3 vs. 72.3 +/- 27.6 s, P
      = 0.020) in normoxia than in hyperoxia. Therefore, the ventilatory responses to
      transient CO2 disturbances are less damped (but generally not oscillatory) in
      normoxia than in hyperoxia. For the closed-loop transfer function, the gain in
      normoxia increased significantly (P < 0.0005), while phase delay decreased
      significantly (P < 0.0005). The gain increased by 108.5, 186.0, and 240.6%, while
      phase delay decreased by 26.0, 18.1, and 17.3%, at 0. 01, 0.03, and 0.05 Hz,
      respectively. Changes in the same direction were found for the open-loop system.
      Generally, an oscillatory ventilatory response to a small transient CO2
      disturbance is unlikely during wakefulness. However, changes in parameters that
      lead to additional increases in chemoreflex loop gain are more likely to initiate
      oscillations in normoxia than in hyperoxia.

PMID- 9262443
TI  - Chronic hormone replacement therapy alters thermoregulatory and vasomotor
      function in postmenopausal women.
AB  - This investigation examined effects of chronic (>/=2 yr) hormone replacement
      therapy (HRT), both estrogen replacement therapy (ERT) and estrogen plus
      progesterone therapy (E+P), on core temperature and skin blood flow responses of
      postmenopausal women. Twenty-five postmenopausal women [9 not on HRT (NO), 8 on
      ERT, 8 on E+P] exercised on a cycle ergometer for 1 h at an ambient temperature
      of 36 degrees C. Cutaneous vascular conductance (CVC) was monitored by laser
      Doppler flowmetry, and forearm vascular conductance (FVC) was measured by using
      venous occlusion plethysmography. Iontophoresis of bretylium tosylate was
      performed before exercise to block local vasoconstrictor (VC) activity at one
      skin site on the forearm. Rectal temperature (Tre) was approximately 0.5 degrees
      C lower for the ERT group (P < 0.01) compared with E+P and NO groups at rest and
      throughout exercise. FVC: mean body temperature (Tb) and CVC: Tb curves were
      shifted approximately 0.5 degrees C leftward for the ERT group (P < 0.0001).
      Baseline CVC was significantly higher in the ERT group (P < 0.05), but there was
      no interaction between bretylium treatment and groups once exercise was
      initiated. These results suggest that 1) chronic ERT likely acts centrally to
      decrease Tre, 2) ERT lowers the Tre at which heat-loss effector mechanisms are
      initiated, primarily by actions on active cutaneous vasodilation, and 3) addition
      of exogenous progestins in HRT effectively blocks these effects.

PMID- 9262444
TI  - Comparative hemodynamic effects of periodic obstructive and simulated central
      apneas in sedated pigs.
AB  - It has been speculated that because of increased left ventricular (LV) afterload,
      decreased intrathoracic pressure (ITP) is responsible for decreased cardiac
      output (CO) in obstructive sleep apnea. If this were true, then obstructive apnea
      (OA) should have a greater effect on CO than would central apnea (CA). To assess
      the importance of decreased ITP during OA, we studied seven preinstrumented
      sedated pigs with OA and simulated CA that were matched for blood gases and apnea
      periodicities (with 15- or 30-s apnea duration). Compared with OA, CA with 30-s
      apnea duration produced comparable decreases in heart rate (from baseline to end
      apnea: OA, 106.6 +/- 4.8 to 93.4 +/- 4.4 beats/min, P < 0.01; and CA, 111.1 +/-
      6.2 to 94.0 +/- 5.2 beats/min, P < 0.01) and comparable increases in LV end
      diastolic pressure and LV end-diastolic myocardial segment length but greater
      increases in mean arterial pressure (97.1 +/- 3.7 to 107.7 +/- 4.3 Torr, P <
      0.05; and 97.3 +/- 4.8 to 119.3 +/- 7.4 Torr, P < 0.01) and systemic vascular
      resistance (2,577 +/- 224 to 3,346 +/- 400 dyn . s . cm-5, P < 0.01; and 2,738 +/
      294 to 5,111 +/- 1,181 dyn . s . cm-5, P < 0.01) and greater decreases in CO
      (3.18 +/- 0.31 to 2.74 +/- 0.26 l/min, P < 0. 05; and 3.07 +/- 0.38 to 2.30 +/-
      0.36 l/min, P < 0.01) and stroke volume (32.2 +/- 2.9 to 25.9 +/- 2.4 ml, P <
      0.05; and 31.5 +/- 1.9 to 19.8 +/- 3.1 ml, P < 0.01). Only CA increased LV end
      systolic myocardial segment length. Similar findings were observed with 15-s
      apnea duration. We conclude that CA produced greater depression of CO and greater
      changes of afterload-related LV dysfunction than did OA. Therefore, decreased ITP
      was not the dominant factor determining LV function with apneas.

PMID- 9262445
TI  - Flow-induced vasodilation in the ferret lung.
AB  - To examine the possibility that shear stress may be a pulmonary vasodilator
      stimulus, we studied the effect of changing blood flow on the diameters of small
      pulmonary arteries in isolated perfused ferret lung lobes. The arteries studied
      were in the approximately 0.3- to 1.3-mm-diameter range, and the diameters were
      measured by using microfocal X-ray imaging. The diameters were measured at two
      flow rates, 10 and 40 ml/min, with the intravascular pressure in the measured
      vessels the same at the two flow rates as the result of venous pressure
      adjustment. The response to a change in flow was studied under both normoxic and
      hypoxic conditions. Hypoxia was used to elevate pulmonary arterial tone to
      increase the likelihood of detecting a vasodilator response. Under normoxic
      conditions, changing flow had little effect on the arterial diameters, but under
      hypoxic conditions the arteries were consistently larger at the higher flow than
      at the lower flow, even though the distending pressure was the same at the two
      flow rates. The results are consistent with the hypothesis that shear stress is a
      pulmonary vasodilator stimulus.

PMID- 9262446
TI  - Enhanced ventilatory and exercise performance in athletes with slight expiratory
      resistive loading.
AB  - We determined the cardiorespiratory and performance effects of slight (1.5-3.0
      cmH2O) expiratory resistive loading (ERL). Twenty-eight highly fit [peak O2
      uptake (VO2 peak) = 63.6 +/- 1.3 ml . kg-1 . min-1] athletes (age = 33.5 +/- 1.3
      yr) performed paired VO2 peak cycle ergometer tests (control vs. ERL). End
      expiratory lung volume was separately determined in a subset of subjects (n = 12)
      at steady-state 75% maximum power output (POmax) and was found to increase (0.67
      +/- 0.29 liter) with ERL. In the VO2 peak tests, peak expiratory pressure at the
      mouth, mean inspiratory flow, minute ventilation, and O2 pulse were greater with
      ERL at every intensity level (i.e., 75, 80, 85, and 90% POmax). Increased minute
      ventilation was largely due to a trend toward increased tidal volume (P < 0.05 at
      80% POmax). O2 uptake was greater at 90% POmax with ERL. Increased O2 pulse with
      ERL at comparative workloads suggests that stroke volume was augmented with ERL.
      Also, with ERL, athletes attained higher VO2 peak (63.0 +/- 1.4 vs. 60.1 +/- 1.3
      ml . kg-1 . min-1) and greater POmax (352.0 +/- 9.9 vs. 345.7 +/- 9.5 W). We
      conclude that elevated end-expiratory lung volume in response to slight ERL
      during strenuous exercise served to attenuate both airflow and blood flow
      limitations, which enhanced exercise capacity.

PMID- 9262448
TI  - Curtailed respiration by repeated vs. isolated hypoxia in maturing piglets is
      unrelated to NTS ME or SP levels.
AB  - In early development, respiratory disorders can produce recurring hypoxic
      episodes during sleep. To examine possible effects of daily repeated vs. isolated
      hypoxic hypoxia, cardiorespiratory functions and central, respiratory-related
      neuromodulator levels in 21- to 32-day-old, chronically instrumented, unsedated
      piglets were compared between a fifth sequential daily hypoxia and an isolated
      hypoxia (10% O2-90% N2 for 30 min). Diaphragmatic electromyographic activity,
      heart rate and arterial pressure, and pH and gas tensions were measured. In vivo
      microdialysis, via chronically implanted guides, served to sample interstitial
      substance P (SP) and methionine-enkephalin (ME) at the level of the respiratory
      related nucleus tractus solitarii (NTS). Compared with an isolated hypoxia,
      repeated hypoxia resulted in 1) lower respiratory frequency (f), ventilation
      equivalent, and arterial pH, higher arterial PO2 during hypoxia, and lower f in
      recovery from hypoxia; and 2) increased SP concentrations but no change in ME
      concentrations. We conclude that, in these maturing swine, repeated vs. isolated
      hypoxic exposure curtails respiratory responses to hypoxia by a mechanism(s)
      unrelated to SP or ME levels at the NTS.

PMID- 9262447
TI  - Impaired calcium pump function does not slow relaxation in human skeletal muscle
      after prolonged exercise.
AB  - This study examined the effects of prolonged exercise on human quadriceps muscle
      contractile function and homogenate sarcoplasmic reticulum Ca2+ uptake and Ca2+
      adenosinetriphosphatase activity. Ten untrained men cycled at 75 +/- 2% (SE) peak
      oxygen consumption until exhaustion. Biopsies were taken from the right vastus
      lateralis muscle at rest, exhaustion, and 20 and 60 min postexercise. Peak
      tension and half relaxation time of the left quadriceps muscle were measured
      during electrically evoked twitch and tetanic contractions and a maximal
      voluntary isometric contraction at rest, exhaustion, and 10, 20, and 60 min
      postexercise. At exhaustion, homogenate Ca2+ uptake and Ca2+
      adenosinetriphosphatase activity were reduced by 17 +/- 4 and 21 +/- 5%,
      respectively, and remained depressed after 60 min recovery (P </= 0.01). Muscle
      ATP, creatine phosphate, and glycogen were all depressed at exhaustion (P </=
      0.01). Peak tension during a maximal voluntary contraction, a twitch, and a 10-Hz
      stimulation were reduced after exercise by 28 +/- 3, 45 +/- 6, 65 +/- 5%,
      respectively (P </= 0.01), but no slowing of half relaxation times were found.
      Thus fatigue induced by prolonged exercise reduced muscle Ca2+ uptake, but this
      did not cause a slower relaxation of evoked contractions.

PMID- 9262449
TI  - Downstream effects of splanchnic ischemia-reperfusion injury on renal function
      and eicosanoid release.
AB  - This study examines the hypothesis that intestinal ischemia-reperfusion (I/R)
      injury contributes to renal dysfunction by altered renal eicosanoid release.
      Anesthetized Sprague-Dawley rats underwent 60 min of sham or superior mesenteric
      artery (SMA) occlusion with 60 min of reperfusion. The I/R groups received either
      allopurinol, pentoxifylline, 1-benzylimidazole, or carrier before SMA occlusion.
      In vivo renal artery blood flow was measured by Transonic flow probes, the
      kidneys were then perfused in vitro for 30 min, and the effluent was analyzed for
      eicosanoid release and renal function. Intestinal I/R caused a twofold increase
      in the ratio of renal release of thromboxane B2 to prostaglandin E2 and to 6
      ketoprostaglandin F1alpha compared with the sham level, with a corresponding 25%
      decrease in renal sodium and inulin clearance and renal blood flow.
      Pentoxifylline or allopurinol pretreatment restored renal eicosanoid release and
      renal sodium and inulin clearance to the sham level but did not alter renal blood
      flow. Pretreatment with 1-benzylimidazole restored renal function, eicosanoid
      release, and renal blood flow to sham levels. These data suggest that severe
      intestinal I/R contributes to the downregulation of renal function. The decrease
      in renal function is due in part to toxic oxygen metabolites, which occur in the
      milieu of altered renal eicosanoid release, reflecting a decrease in vasodilator
      and an increase in vasoconstrictor eicosanoids.

PMID- 9262450
TI  - Effect of 2,4-dinitrophenol on the hypometabolic response to hypoxia of conscious
      adult rats.
AB  - During acute hypoxia, a hypometabolic response is commonly observed in many
      newborn and adult mammalian species. We hypothesized that, if hypoxic
      hypometabolism were entirely a regulated response with no limitation in O2
      availability, pharmacological uncoupling of the oxidative phosphorylation should
      raise O2 consumption (VO2) by similar amounts in hypoxia and normoxia. Metabolic,
      ventilatory, and cardiovascular measurements were collected from conscious rats
      in air and in hypoxia, both before and after intravenous injection of the
      mitochondrial uncoupler 2,4-dinitrophenol (DNP). In hypoxia (10% O2 breathing,
      60% arterial O2 saturation), VO2, as measured by an open-flow technique, was less
      than in normoxia (approximately 80%). Successive DNP injections (6 mg/kg, 4
      times) progressively increased VO2 in both normoxia and hypoxia by similar
      amounts. Body temperature slightly increased in normoxia, whereas it did not
      change in hypoxia. The DNP-stimulated VO2 during hypoxia could even exceed the
      control normoxic value. A single DNP injection (17 mg/kg iv) had a similar
      metabolic effect; it also resulted in hypotension and a drop in systemic vascular
      resistance. We conclude that pharmacological stimulation of VO2 counteracts the
      VO2 drop determined by hypoxia and stimulates VO2 not dissimilarly from normoxia.
      Hypoxic hypometabolism is likely to reflect a regulated process of depression of
      thermogenesis, with no limitation in cellular O2 availability.

PMID- 9262451
TI  - Capillary recruitment and transit time in the rat lung.
AB  - Increasing pulmonary blood flow and the associated rise in capillary perfusion
      pressure cause capillary recruitment. The resulting increase in capillary volume
      limits the decrease in capillary transit time. We hypothesize that small species
      with relatively high resting metabolic rates are more likely to utilize a larger
      fraction of gas-exchange reserve at rest. Without reserve, we anticipate that
      capillary transit time will decrease rapidly as pulmonary blood flow rises. To
      test this hypothesis, we measured capillary recruitment and transit time in
      isolated rat lungs. As flow increased, transit time decreased, and capillaries
      were recruited. The decrease in transit time was limited by an increase in the
      homogeneity of the transit time distribution and an increased capillary volume
      due, in part, to recruitment. The recruitable capillaries, however, were nearly
      completely perfused at flow rates and pressures that were less than basal for the
      intact animal. This suggests that a limited reserve of recruitable capillaries in
      the lungs of species with high resting metabolic rates may contribute to their
      inability to raise O2 consumption manyfold above basal values.

PMID- 9262452
TI  - Aerosolized manganese SOD decreases hyperoxic pulmonary injury in primates. I.
      Physiology and biochemistry.
AB  - Prolonged hyperoxia causes lung injury and respiratory failure secondary to
      oxidative tissue damage mediated, in part, by the superoxide anion. We
      hypothesized that aerosol treatment with recombinant human manganese superoxide
      dismutase (rhMnSOD) would attenuate hyperoxic lung damage in primates. Adult
      baboons were anesthetized and ventilated with 100% oxygen for 96 h or until
      death. Six animals were treated with aerosolized rhMnSOD (3 mg . kg-1 . day-1 in
      divided doses), and six control animals did not receive enzyme therapy.
      Physiological variables were recorded every 12 h, and ventilation-perfusion ratio
      relationships were evaluated by using the multiple inert-gas elimination
      technique. After the experiments, surfactant composition and lung edema were
      measured. We found that rhMnSOD significantly decreased pulmonary shunt fraction
      (P < 0.01) and preserved arterial oxygenation (P < 0.01) during hyperoxia. The
      rhMnSOD increased lung phospholipids, phosphatidylcholine and disaturated
      phosphatidylcholine, and decreased lung edema in this model. Testing of higher
      and lower doses of MnSOD (1 and 10 mg . kg-1 . day-1) in two other groups of
      baboons produced variable physiological protection, suggesting a "window" of
      effective dosage. We conclude that aerosolized MnSOD (3 mg . kg-1 . day-1)
      affords significant preservation of pulmonary gas exchange during hyperoxic lung
      injury.

PMID- 9262453
TI  - Aerosolized manganese SOD decreases hyperoxic pulmonary injury in primates. II.
      Morphometric analysis.
AB  - Hyperoxia damages lung parenchyma via increased cellular production of reactive
      oxygen species that exceeds antioxidant defenses. We hypothesized that
      aerosolized human recombinant manganese superoxide dismutase (rhMnSOD) would
      augment extracellular antioxidant defenses and attenuate epithelial injury in the
      lung during hyperoxia in primates. Twenty-four adult male baboons were
      anesthetized and mechanically ventilated with 100% oxygen for 96 h. The baboons
      were divided equally into four groups. Oxygen alone and oxygen plus rhMnSOD given
      at 3 mg . kg-1 . day-1 were compared to assess efficacy of the drug.
      Subsequently, aerosolized rhMnSOD was given at 1 or 10 mg . kg-1 . day-1 to study
      dose effects and toxicity. Quantitative morphometry showed protection of alveolar
      epithelium from hyperoxia by 3 mg . kg-1 . day-1 rhMnSOD (P < 0.05). In addition,
      interstitial fibroblast volumes were increased in the treatment group (P = 0.06).
      This effect appeared greater at the two higher doses of the rhMnSOD. The
      aerosolized drug was localized to the surface of airways and air spaces and
      macrophages by immunolabeling studies, suggesting efficacy via physicochemical
      properties that localize it to cell surfaces or by effects on alveolar macrophage
      function.

PMID- 9262455
TI  - EEG and sleep disturbances during dives at 450 msw in helium-nitrogen-oxygen
      mixture.
AB  - To study the effects of nitrogen addition to the breathing mixture on sleep
      disturbances at pressure, two dives were performed in which helium-nitrogen
      oxygen mixture was used up to 450 m sea water (msw). In total, sleep of 12
      professional divers was analyzed (i.e., 184 night records). Sleep was disrupted
      by compression and by stay at 450 msw: we observed an increase in awake periods
      and in sleep stages I and II and a decrease in stages III and IV and in rapid-eye
      movement sleep periods. These changes, which were more intense at the beginning
      of the stay, began to decrease from the seventh day of the stay, but the return
      to control values was recorded only during the decompression at depths below 200
      msw. These changes were equivalent to those recorded in other experiments with
      helium-oxygen mixture in the same range of depths and were independent of the
      intensity of changes recorded in electroencephalographic activities in awake
      subjects.

PMID- 9262454
TI  - Pulmonary vasoreactivity to serotonin during hypoxia is modulated by ATP
      sensitive potassium channels.
AB  - The role of ATP-sensitive K+-channel modulation in the canine pulmonary vascular
      response to serotonin during hypoxia was determined in the isolated blood
      perfused dog lung. Pulmonary vascular resistances and compliances were measured
      by using vascular occlusion techniques. Under normoxia, serotonin (10(-5) M)
      significantly increased precapillary and postcapillary resistances and pulmonary
      capillary pressure and decreased total vascular compliance by decreasing both
      microvascular and large-vessel compliances. During hypoxia, the effect of
      serotonin was potentiated on both precapillary and postcapillary resistance and
      capillary pressure, as well as on microvascular compliance and large-vessel
      compliance. Under normoxia, the ATP-sensitive K+-channel opener cromakalim (10(
      5) M) inhibited the serotonergic response on postcapillary resistance and
      microvascular compliance, whereas during hypoxia cromakalim inhibited the
      potentiated effect of serotonin on both precapillary and postcapillary
      resistance, capillary pressure, and both microvascular and large-vessel
      compliances. These results indicate that canine pulmonary vasoreactivity to
      serotonin is heightened under hypoxic conditions and that ATP-sensitive K+
      channels modulate the pressor response to serotonin, an effect that is more
      pronounced during hypoxia.

PMID- 9262457
TI  - Effects of chest wall counterpressures on lung mechanics under high levels of
      CPAP in humans.
AB  - We assessed the respective effects of thoracic (TCP) and abdominal/lower limb
      (ACP) counterpressures on end-expiratory volume (EEV) and respiratory muscle
      activity in humans breathing at 40 cmH2O of continuous positive airway pressure
      (CPAP). Expiratory activity was evaluated on the basis of the inspiratory drop in
      gastric pressure (DeltaPga) from its maximal end-expiratory level, whereas
      inspiratory activity was evaluated on the basis of the transdiaphragmatic
      pressure-time product (PTPdi). CPAP induced hyperventilation (+320%) and only a
      28% increase in EEV because of a high level of expiratory activity (DeltaPga = 24
      +/- 5 cmH2O), contrasting with a reduction in PTPdi from 17 +/- 2 to 9 +/- 7
      cmH2O . s-1 . cycle-1 during 0 and 40 cmH2O of CPAP, respectively. When ACP, TCP,
      or both were added, hyperventilation decreased and PTPdi increased (19 +/- 5, 21
      +/- 5, and 35 +/- 7 cmH2O . s-1 . cycle-1, respectively), whereas DeltaPga
      decreased (19 +/- 6, 9 +/- 4, and 2 +/- 2 cmH2O, respectively). We concluded that
      during high-level CPAP, TCP and ACP limit lung hyperinflation and expiratory
      muscle activity and restore diaphragmatic activity.

PMID- 9262456
TI  - PGE1, dexamethasone, U-74389G, or Bt2-cAMP as an additive to promote protection
      by UW solution in I/R injury.
AB  - A method to reduce ischemia-reperfusion (I/R) injury can be an important
      criterion to improve the preservation solution. Although University of Wisconsin
      solution (UW) works as a lung preservation solution, its attenuation effect on
      I/R injury has not been investigated. We attempted to determine whether, by
      adding various protective agents, modified UW solutions will enhance the I/R
      attenuation by UW. We examined the I/R injury in an isolated rat lung model.
      Various solutions, e.g., physiological salt solution (PSS), UW, and modified UW
      solutions containing various protective agents such as prostaglandin E1,
      dexamethasone, U-74389G, or dibutyryl adenosine 3',5'-cyclic monophosphate were
      perfused individually to evaluate the I/R injury. Isolated rat lung experiments,
      with ischemia for 45 min, then reperfusion for 60 min, were conducted in a closed
      circulating system. Hemodynamic changes, lung weight gain (LWG), capillary
      filtration coefficient (Kfc), protein content of lavage fluid, concentration of
      cytokines, and lung histopathology were analyzed. Results showed that the acute
      I/R lung injury with immediate permeability pulmonary edema was associated with
      an increase in tumor necrosis factor-alpha (TNF-alpha) production. A significant
      correlation existed between TNF-alpha and Kfc (r = 0.8, P < 0.0001) and TNF-alpha
      and LWG (r = 0. 9, P < 0.0001), indicating that TNF-alpha is an important
      cytokine modulating early I/R injury. Significantly lower levels of Kfc, LWG, TNF
      alpha, and protein concentration of lung lavage (P < 0.05) were found in the UW
      perfused group than in the control group perfused with PSS. Modified UW promoted
      the protective effect of UW to further decrease Kfc, LWG, and TNF-alpha (P <
      0.05). Histopathological observations also substantiated this evidence. In the
      UW+U-74389G group, bronchial alveolar lavage fluid contained lowest protein
      concentration. We conclude that the UW solution attenuates I/R injury of rat lung
      and that the modified UW solutions further enhance the effect of UW in reducing
      I/R injury. Among modified solutions, UW+U-74389G is the best. Further
      investigation of the improved effects of the modified UW solutions would be
      beneficial in lung transplantation.

PMID- 9262458
TI  - Comparison of effects of sustained isocapnic hypoxia on ventilation in men and
      women.
AB  - Sleep-related respiratory disturbances are more common in men than in
      premenopausal women. This might, in part, be due to different susceptibilities to
      the respiratory depressant effects of hypoxia. Therefore, we compared ventilation
      during 10 min of baseline room-air breathing and 20-min sustained isocapnic
      hypoxia (fractional inspired O2 = 11%, arterial saturation of O2 approximately
      80%) followed by 10 min of breathing 100% O2 in 10 normal men and in 10 women in
      the follicular phase of the menstrual cycle. Control measurements were made
      during two transitions from room air (10 min) to 100% O2 (10 min) and averaged.
      Inspired minute ventilation (VI) after 2 min of hypoxia was the same in men and
      women [131 +/- 6.1% baseline for men, 136 +/- 7.7% baseline for women; not
      significant (NS)] and declined to the same level after 20 min (115 +/- 5.0%
      baseline for men, 116 +/- 6.6% baseline for women; NS) associated with a similar
      decline in inspiratory time and tidal volume. Breathing frequency did not change.
      VI decreased transiently during subsequent 100% O2 breathing in both men and
      women, associated with reduced frequency and duty cycle and increased expiratory
      time. The fall in VI was significantly greater than that observed during control
      hyperoxia experiments in men but not in women. We conclude that ventilatory
      responses to sustained isocapnic hypoxia do not differ between awake healthy men
      and women in the follicular phase of their menstrual cycle. However, after
      termination of isocapnic hypoxia, men appear to depress their ventilation to a
      greater degree than women.

PMID- 9262459
TI  - Oral glucose ingestion increases endurance capacity in normal and diabetic (type
      I) humans.
AB  - The effects of an oral glucose administration (1 g/kg) 30 min before exercise on
      endurance capacity and metabolic responses were studied in 21 type I diabetic
      patients [insulin-dependent diabetes mellitus (IDDM)] and 23 normal controls
      (Con). Cycle ergometer exercise (55-60% of maximal O2 uptake) was performed until
      exhaustion. Glucose administration significantly increased endurance capacity in
      Con (112 +/- 7 vs. 125 +/- 6 min, P < 0.05) but only in IDDM patients whose blood
      glucose decreased during exercise (70.8 +/- 8.2 vs. 82.8 +/- 9.4 min, P < 0.05).
      Hyperglycemia was normalized at 15 min of exercise in Con (7.4 +/- 0.2 vs. 4.8 +/
      0.2 mM) but not in IDDM patients (12.4 +/- 0.7 vs. 15.6 +/- 0.9 mM). In Con,
      insulin and C-peptide levels were normalized during exercise. Glucose
      administration decreased growth hormone levels in both groups. In conclusion,
      oral glucose ingestion 30 min before exercise increases endurance capacity in Con
      and in some IDDM patients. In IDDM patients, in contrast with Con, exercise to
      exhaustion attenuates hyperglycemia but does not bring blood glucose levels to
      preglucose levels.

PMID- 9262460
TI  - Role for anions in pulmonary endothelial permeability.
AB  - beta-Adrenergic stimulation reduces albumin permeation across pulmonary artery
      endothelial monolayers and induces changes in cell morphology that are mediated
      by Cl- flux. We tested the hypothesis that anion-mediated changes in endothelial
      cells result in changes in endothelial permeability. We measured permeation of
      radiolabeled albumin across bovine pulmonary arterial endothelial monolayers when
      the extracellular anion was Cl-, Br-, I-, F-, acetate (Ac-), gluconate (G-), and
      propionate (Pr-). Permeability to albumin (Palbumin) was calculated before and
      after addition of 0.2 mM of the phosphodiesterase inhibitor 3-isobutyl-1
      methylxanthine (IBMX), which reduces permeability. In Cl-, the Palbumin was 3.05
      +/- 0.86 x 10(-6) cm/s and fell by 70% with the addition of IBMX. The initial
      Palbumin was lowest for Pr- and Ac-. Initial Palbumin was higher in Br-, I-, G-,
      and F- than in Cl-. A permeability ratio was calculated to examine the IBMX
      effect. The greatest IBMX effect was seen when Cl- was the extracellular anion,
      and the order among halide anions was Cl- > Br- > I- > F-. Although the level of
      extracellular Ca2+ concentration ([Ca2+]o) varied over a wide range in the anion
      solutions, [Ca2+]o did not systematically affect endothelial permeability in this
      system. When Cl- was the extracellular anion, varying [Ca2+]o from 0.2 to 2.8 mM
      caused a change in initial Palbumin but no change in the IBMX effect. The anion
      channel blockers 4-acetamido-4'-isothiocyanotostilbene-2, 2'-disulfonic acid
      (0.25 mM) and anthracene-9-carboxylic acid (0.5 mM) significantly altered initial
      Palbumin and the IBMX effect. The anion transport blockers bumetanide (0.2 mM)
      and furosemide (1 mM) had no such effects. We conclude that extracellular anions
      influence bovine pulmonary arterial endothelial permeability and that the
      pharmacological profile fits better with the activity of anion channels than with
      other anion transport processes.

PMID- 9262461
TI  - In vivo validation of whole body composition estimates from dual-energy X-ray
      absorptiometry.
AB  - We validated whole body composition estimates from dual-energy X-ray
      absorptiometry (DEXA) against estimates from a four-component model to determine
      whether accuracy is affected by gender, race, athletic status, or musculoskeletal
      development in young adults. Measurements of body density by hydrostatic
      weighing, body water by deuterium dilution, and bone mineral by whole body DEXA
      were obtained in 172 young men (n = 91) and women (n = 81). Estimates of body fat
      (%Fat) from DEXA (%FatDEXA) were highly correlated with estimates of body fat
      from the four-component model [body density, total body water, and total body
      mineral (%Fatd,w,m); r = 0.94, standard error of the estimante (SEE) = 2.8% body
      mass (BM)] with no significant difference between methods [mean of the difference
      +/- SD of the difference = -0.4 +/- 2.9 (SD) % BM, P = 0.10] in women and men. On
      the basis of the comparison with %Fatd,w,m, estimates of %FatDEXA were slightly
      more accurate than those from body density (r = 0.91, SEE = 3.4%; mean of the
      difference +/- SD of the difference = -1.2 +/- 3.4% BM). Differences between
      %FatDEXA and %Fatd,w,m were weakly related to body thickness, as reflected by BMI
      (r = -0.34), and to the percentage of water in the fat-free mass (r = -0.51), but
      were not affected by race, athletic status, or musculoskeletal development. We
      conclude that body composition estimates from DEXA are accurate compared with
      those from a four-component model in young adults who vary in gender, race,
      athletic status, body size, musculoskeletal development, and body fatness.

PMID- 9262462
TI  - Mechanism of the exercise hyperkalemia: an alternate hypothesis.
AB  - A progressive hyperkalemia is observed as exercise intensity increases. The
      current most popular hypothesis for the hyperkalemia is that the Na+-K+ pump
      cannot keep pace with the K+ efflux from muscle during the depolarization
      repolarization process of the sarcolemmal membrane during muscle contraction. In
      this report, we present data that suggest an alternate hypothesis to those
      previously described. Because phosphocreatine (PCr) is a highly dissociated acid
      and creatine is neutral at cell pH, the concentration of nondiffusible anions
      decreases, and an alkaline reaction takes place when PCr hydrolyzes. This creates
      a state of cation (K+) excess and H+ depletion in the cell. To examine the
      balance of K+ and H+ for exercising muscle during the early period of exercise
      when PCr changes most rapidly, catheters were inserted into the brachial artery
      and femoral vein (FV) in five healthy subjects who performed two 6-min cycle
      ergometer exercise tests at 40 and 85% of peak oxygen uptake. FV blood was
      sampled every 5 s during the first 2 min, then every 30 s for the remaining 4 min
      of exercise and the first 3 min of recovery, and then less frequently for the
      next 12 min. Arterial sampling was every 30 s during exercise and simultaneous
      with FV sampling during recovery. Arterial K+ concentration ([K+]) increase
      lagged FV [K+] increase. The hyperkalemia observed during early exercise results
      from K+ release from skeletal muscle. FV [K+] increased by 5 s of the start of
      exercise and followed the rate of H+ loss from the FV blood for the first 30 s of
      exercise. FV lactate and Na+ kinetics differed from K+ kinetics during exercise
      and recovery. As predicted from the PCr hydrolysis reaction, the exercising limb
      took up H+ and released K+ at the start of exercise (first 30 s) at both exercise
      intensities, resulting in a FV metabolic alkalosis. K+ release was essentially
      complete by 3 min, the time at which oxygen uptake (and, presumably, PCr) reached
      its asymptote. These findings lead us to hypothesize that the early K+ release by
      the cell takes place with H+ exchange and that the major mechanism for the
      exercise hyperkalemia is the reduction in nondiffusible intracellular anions in
      the myocyte as PCr hydrolyzes.

PMID- 9262463
TI  - Acid-base regulation after maximal exercise testing in late gestation.
AB  - This study employed Stewart's physicochemical approach to quantify the effects of
      pregnancy and strenuous exercise on the independent determinants of plasma H+
      concentration ([H+]). Subjects were nine physically active pregnant women [mean
      gestational age = 33 +/- 1 (SE) wk] and 14 age-matched nonpregnant controls.
      Venous blood samples and respiratory data were obtained at rest and during 15 min
      of recovery from a maximal cycle ergometer test that involved 20 W/min increases
      in work rate to exhaustion. Mean values for [H+], PCO2, and total protein
      increased, whereas those for bicarbonate concentration ([HCO-3]) and the strong
      ion difference ([SID]) decreased in the transition from rest to maximal exercise
      within both groups. At rest and throughout postexercise recovery, the pregnant
      group exhibited significantly lower mean values for PCO2, [HCO-3], and total
      protein, whereas [SID] was significantly lower at rest and early recovery from
      exercise. [H+] was also lower at all sampling times in the pregnant group, but
      this effect was significant only at rest. Our results support the hypothesis that
      reduced PCO2 and weak acid concentration are important mechanisms to regulate
      plasma [H+] and to maintain a less acidic plasma environment at rest and after
      exercise in late gestation compared with the nonpregnant state. These effects are
      established in the resting state and appear to be maintained after maximal
      exertion.

PMID- 9262464
TI  - Effect of inotropic interventions on contraction and Ca2+ transients in the human
      heart.
AB  - The present study investigated the influences of inotropic intervention on the
      intracellular Ca2+ transient (intracellular Ca2+ concentration ([Ca2+]i)) and
      contractile twitch. Isometric twitch and [Ca2+]i (fura 2 ratio method) were
      measured simultaneously (1 Hz, 37 degrees C) after stimulation with Ca2+ (0.9-3.2
      mM), the cardiac glycoside ouabain (Oua; 0.1 microM), the beta1- and beta2
      adrenoceptor-agonist isoprenaline (Iso; 1-10 nM), and the Ca2+ sensitizer EMD
      57033 (30 microM) by using isolated human nonfailing right auricular trabeculae
      (n = 19). Inotropic interventions increased force of contraction and peak rate of
      tension rise (+T) significantly. Only Iso stimulated peak rate of tension decay (
      T) higher than +T (P < 0.05), thereby reducing time of contraction (Ttwitch). EMD
      57033 increased +T more effectively than -T and prolonged Ttwitch (P < 0.05).
      Ca2+, Oua, and Iso, but not EMD-57033, increased systolic Ca2+. Diastolic Ca2+
      increased after stimulation with Oua or Ca2+, but not in the presence of EMD
      57033. Iso shortened the Ca2+ transient and did not influence diastolic Ca2+. In
      conclusion, positive inotropic agents differently affect force and [Ca2+]i
      depending on their mode of action. Inotropic interventions influence diastolic
      Ca2+ and thus may be less advantageous in a situation with altered intracellular
      Ca2+ homeostasis (e.g., heart failure due to dilated cardiomyopathy).

PMID- 9262465
TI  - Exercise performance of Tibetan and Han adolescents at altitudes of 3,417 and
      4,300 m.
AB  - The difference was studied between O2 transport in lifelong Tibetan adolescents
      and in newcomer Han adolescents acclimatized to high altitude. We measured minute
      ventilation, maximal O2 uptake, maximal cardiac output, and arterial O2
      saturation during maximal exercise, using the incremental exercise technique, at
      altitudes of 3,417 and 4,300 m. The groups were well matched for age, height, and
      nutritional status. The Tibetans had been living at the altitudes for a longer
      period than the Hans (14.5 +/- 0.2 vs. 7.8 +/- 0.8 yr at 3,417 m, P < 0.01; and
      14.7 +/- 0.3 vs. 5.3 +/- 0.7 yr at 4,300 m, P < 0.01, respectively). At rest,
      Tibetans had significantly greater vital capacity and maximal voluntary
      ventilation than the Hans at both altitudes. At maximal exercise, Tibetans
      compared with Hans had higher maximal O2 uptake (42.2 +/- 1.7 vs. 36.7 +/- 1.2 ml
      . min-1 . kg-1 at 3,417 m, P < 0.01; and 36.8 +/- 1.9 vs. 30.0 +/- 1. 4 ml . min
      1 . kg-1 at 4,300 m, P < 0.01, respectively) and greater maximal cardiac output
      (12.8 +/- 0.3 vs. 11.4 +/- 0.2 l/min at 3,417 m, P < 0.01; 11.5 +/- 0.5 vs. 10.0
      +/- 0.5 l/min at 4,300 m, P < 0. 05, respectively). Although the differences in
      arterial O2 saturation between Tibetans and Hans were not significant at rest and
      during mild exercise, the differences became greater with increases in exercise
      workload at both altitudes. We concluded that exposure to high altitude from
      birth to adolescence resulted in an efficient O2 transport and a greater aerobic
      exercise performance that may reflect a successful adaptation to life at high
      altitude.

PMID- 9262466
TI  - Airway thermal volume in humans and its relation to body size.
AB  - The objective of this study was to investigate the influence of volume
      ventilation (VE) and cardiac output (Q) on the temperature of the expired gas at
      the distal end of the endotracheal tube in anesthetized humans. In 63
      mechanically ventilated adults, we used a step decrease in the humidity of
      inspired gas to cool the lungs. After change from humid to dry gas ventilation,
      the temperature of the expired gas decreased. We evaluated the relationship
      between the inverse monoexponential time constant of the temperature fall (1/tau)
      and either VE or Q. When VE was increased from 5.67 +/- 1.28 to 7.14 +/- 1.60
      (SD) l/min (P = 0. 02), 1/tau did not change significantly [from 1.25 +/- 0.38 to
      1.21 +/- 0.51 min-1, P = 0.81]. In the 11 patients in whom Q changed during the
      study period (from 5.07 +/- 1.81 to 7.38 +/- 2.45 l/min, P = 0.02), 1/tau
      increased correspondingly from 0.89 +/- 0.22 to 1. 52 +/- 0.44 min-1 (P = 0.003).
      We calculated the airway thermal volume (ATV) as the ratio of the measured values
      Q to 1/tau and related it to the body height (BH): ATV (liters) = 0.086 BH (cm) -
      9. 55 (r = 0.90).

PMID- 9262467
TI  - Seed banks and molecular maps: unlocking genetic potential from the wild.
AB  - Nearly a century has been spent collecting and preserving genetic diversity in
      plants. Germplasm banks-living seed collections that serve as repositories of
      genetic variation-have been established as a source of genes for improving
      agricultural crops. Genetic linkage maps have made it possible to study the
      chromosomal locations of genes for improving yield and other complex traits
      important to agriculture. The tools of genome research may finally unleash the
      genetic potential of our wild and cultivated germplasm resources for the benefit
      of society.

PMID- 9262469
TI  - Sulfur and hydrogen isotope anomalies in meteorite sulfonic acids.
AB  - Intramolecular carbon, hydrogen, and sulfur isotope ratios were measured on a
      homologous series of organic sulfonic acids discovered in the Murchison
      meteorite. Mass-independent sulfur isotope fractionations were observed along
      with high deuterium/hydrogen ratios. The deuterium enrichments indicate formation
      of the hydrocarbon portion of these compounds in a low-temperature environment
      that is consistent with that of interstellar clouds. Sulfur-33 enrichments
      observed in methanesulfonic acid could have resulted from gas-phase ultraviolet
      irradiation of a precursor, carbon disulfide. The source of the sulfonic acid
      precursors may have been the reactive interstellar molecule carbon monosulfide.

PMID- 9262473
TI  - Natural (Mg,Fe)SiO3-ilmenite and -perovskite in the Tenham meteorite.
AB  - The minerals (Mg,Fe)SiO3-ilmenite and -perovskite were identified in the shock
      induced veins in the Tenham chondritic meteorite. Both phases are inferred to
      have transformed from pyroxene at high pressures and temperatures by shock
      metamorphism. Columnar-shaped ilmenite grains, one of two types of morphologies,
      have a topotaxial relationship with neighboring pyroxene grains, indicating shear
      transformation. Granular-shaped perovskite grains showed a diffraction pattern
      consistent with orthorhombic perovskite, but these grains were not stable under
      the electron beam irradiation and became amorphous. The higher iron concentration
      in both phases compared with those experimentally reported may suggest their
      metastable transition from enstatite because of shock compression.

PMID- 9262471
TI  - Selective colorimetric detection of polynucleotides based on the distance
      dependent optical properties of gold nanoparticles.
AB  - A highly selective, colorimetric polynucleotide detection method based on
      mercaptoalkyloligonucleotide-modified gold nanoparticle probes is reported.
      Introduction of a single-stranded target oligonucleotide (30 bases) into a
      solution containing the appropriate probes resulted in the formation of a
      polymeric network of nanoparticles with a concomitant red-to-pinkish/purple color
      change. Hybridization was facilitated by freezing and thawing of the solutions,
      and the denaturation of these hybrid materials showed transition temperatures
      over a narrow range that allowed differentiation of a variety of imperfect
      targets. Transfer of the hybridization mixture to a reverse-phase silica plate
      resulted in a blue color upon drying that could be detected visually. The
      unoptimized system can detect about 10 femtomoles of an oligonucleotide.

PMID- 9262474
TI  - Size variation in Middle Pleistocene humans.
AB  - It has been suggested that European Middle Pleistocene humans, Neandertals, and
      prehistoric modern humans had a greater sexual dimorphism than modern humans.
      Analysis of body size variation and cranial capacity variation in the large
      sample from the Sima de los Huesos site in Spain showed instead that the sexual
      dimorphism is comparable in Middle Pleistocene and modern populations.

PMID- 9262476
TI  - A macrophage invasion mechanism of pathogenic mycobacteria.
AB  - Tuberculosis is the leading cause of death due to an infectious organism, killing
      an estimated 3 million people annually. Mycobacterium tuberculosis, the causative
      agent of tuberculosis, and other pathogenic mycobacteria require entry into host
      macrophages to initiate infection. An invasion mechanism was defined that was
      shared among pathogenic mycobacteria including M. tuberculosis, M. leprae, and M.
      avium but not by nonpathogenic mycobacteria or nonmycobacterial intramacrophage
      pathogens. This pathway required the association of the complement cleavage
      product C2a with mycobacteria resulting in the formation of a C3 convertase. The
      mycobacteria-associated C2a cleaved C3, resulting in C3b opsonization of the
      mycobacteria and recognition by macrophages.

PMID- 9262477
TI  - Functional role of high-affinity anandamide transport, as revealed by selective
      inhibition.
AB  - Anandamide, an endogenous ligand for central cannabinoid receptors, is released
      from neurons on depolarization and rapidly inactivated. Anandamide inactivation
      is not completely understood, but it may occur by transport into cells or by
      enzymatic hydrolysis. The compound N-(4-hydroxyphenyl)arachidonylamide (AM404)
      was shown to inhibit high-affinity anandamide accumulation in rat neurons and
      astrocytes in vitro, an indication that this accumulation resulted from carrier
      mediated transport. Although AM404 did not activate cannabinoid receptors or
      inhibit anandamide hydrolysis, it enhanced receptor-mediated anandamide responses
      in vitro and in vivo. The data indicate that carrier-mediated transport may be
      essential for termination of the biological effects of anandamide, and may
      represent a potential drug target.

PMID- 9262478
TI  - An NGF-TrkA-mediated retrograde signal to transcription factor CREB in
      sympathetic neurons.
AB  - Nerve growth factor (NGF) is a neurotrophic factor secreted by cells that are the
      targets of innervation of sympathetic and some sensory neurons. However, the
      mechanism by which the NGF signal is propagated from the axon terminal to the
      cell body, which can be more than 1 meter away, to influence biochemical events
      critical for growth and survival of neurons has remained unclear. An NGF-mediated
      signal transmitted from the terminals and distal axons of cultured rat
      sympathetic neurons to their nuclei regulated phosphorylation of the
      transcription factor CREB (cyclic adenosine monophosphate response element
      binding protein). Internalization of NGF and its receptor tyrosine kinase TrkA,
      and their transport to the cell body, were required for transmission of this
      signal. The tyrosine kinase activity of TrkA was required to maintain it in an
      autophosphorylated state upon its arrival in the cell body and for propagation of
      the signal to CREB within neuronal nuclei. Thus, an NGF-TrkA complex is a
      messenger that delivers the NGF signal from axon terminals to cell bodies of
      sympathetic neurons.

PMID- 9262479
TI  - Hypermethylated SUPERMAN epigenetic alleles in arabidopsis.
AB  - Mutations in the SUPERMAN gene affect flower development in Arabidopsis. Seven
      heritable but unstable sup epi-alleles (the clark kent alleles) are associated
      with nearly identical patterns of excess cytosine methylation within the SUP gene
      and a decreased level of SUP RNA. Revertants of these alleles are largely
      demethylated at the SUP locus and have restored levels of SUP RNA. A transgenic
      Arabidopsis line carrying an antisense methyltransferase gene, which shows an
      overall decrease in genomic cytosine methylation, also contains a hypermethylated
      sup allele. Thus, disruption of methylation systems may yield more complex
      outcomes than expected and can result in methylation defects at known genes. The
      clark kent alleles differ from the antisense line because they do not show a
      general decrease in genomic methylation.

PMID- 9262480
TI  - In situ activation pattern of Drosophila EGF receptor pathway during development.
AB  - Signaling cascades triggered by receptor tyrosine kinases (RTKs) participate in
      diverse developmental processes. The active state of these signaling pathways was
      monitored by examination of the in situ distribution of the active, dual
      phosphorylated form of mitogen-activated protein kinase (ERK) with a specific
      monoclonal antibody. Detection of the active state of the Drosophila epidermal
      growth factor receptor (DER) pathway allowed the visualization of gradients and
      boundaries of receptor activation, assessment of the distribution of activating
      ligands, and analysis of interplay with the inhibitory ligand Argos. This in situ
      approach can be used to monitor other receptor-triggered pathways in a wide range
      of organisms.

PMID- 9262482
TI  - Altered neural cell fates and medulloblastoma in mouse patched mutants.
AB  - The PATCHED (PTC) gene encodes a Sonic hedgehog (Shh) receptor and a tumor
      suppressor protein that is defective in basal cell nevus syndrome (BCNS).
      Functions of PTC were investigated by inactivating the mouse gene. Mice
      homozygous for the ptc mutation died during embryogenesis and were found to have
      open and overgrown neural tubes. Two Shh target genes, ptc itself and Gli, were
      derepressed in the ectoderm and mesoderm but not in the endoderm. Shh targets
      that are, under normal conditions, transcribed ventrally were aberrantly
      expressed in dorsal and lateral neural tube cells. Thus Ptc appears to be
      essential for repression of genes that are locally activated by Shh. Mice
      heterozygous for the ptc mutation were larger than normal, and a subset of them
      developed hindlimb defects or cerebellar medulloblastomas, abnormalities also
      seen in BCNS patients.

PMID- 9262484
TI  - Advances and perspectives in acne therapy.
AB  - Acne is one of the most common diseases in dermatology. It is of considerable
      esthetic significance, which explains the mental stress in affected patients.
      Although acne almost always heals spontaneously in early adulthood, treatment
      measures can shorten the course, reduce the severity of the disease, and avoid
      complications such as scarring. Treatment has changed substantially in recent
      years. In accordance with pathogenic principles, effective treatment is possible.
      In most patients, a combination of drugs aimed at correcting abnormal
      keratinization and reducing the proliferation of Propionibacterium acnes is
      sufficient to control the disease. For more severely affected patients with no
      response to this approach, therapy to suppress sebum production is indicated. Of
      all therapeutic modalities available, only oral isotretinoin alters the natural
      course of the disease. In acne inversa, surgical management should be undertaken
      as early as possible.

PMID- 9262483
TI  - Epidermal cell differentiation in Arabidopsis determined by a Myb homolog, CPC.
AB  - The roots of plants normally carry small hairs arranged in a regular pattern.
      Transfer DNA-tagged lines of Arabidopsis thaliana included a mutant with few,
      randomly distributed root hairs. The mutated gene CAPRICE (CPC) encoded a protein
      with a Myb-like DNA binding domain typical of transcription factors involved in
      animal and plant development. Analysis in combination with other root hair
      mutations showed that CPC may work together with the TTG gene and upstream of the
      GL2 gene. Transgenic plants overexpressing CPC had more root hairs and fewer
      trichomes than normal. Thus, the CPC gene determines the fate of epidermal cell
      differentiation in Arabidopsis.

PMID- 9262485
TI  - Effect of a nasal challenge with endotoxin-containing swine confinement dust on
      nasal nitric oxide production.
AB  - Inhalation of swine confinement dust containing endotoxin causes an inflammatory
      response in the nose as reflected by an influx of neutrophils 3 hrs after
      exposure (Am J Respir Crit Care Med 149: A401(1994)). As there is evidence that
      nitric oxide (NO) in exhaled air indicates cellular activation, we studied
      whether endotoxin causes an increase in nasal NO production in human subjects.
      Seven healthy subjects underwent a nasal challenge in which 50 mg swine
      confinement dust was given into each nostril (endotoxin concentration, 23.6
      microg . g-1). Exhaled NO was measured before and during 3 hrs after the
      challenge and was compared to control values measured over the same period of
      time. Endotoxin produced a slight but statistically significant (p = 0.017)
      increase in nasal NO concentrations, mean (+/-SEM) values over 3 hrs being 367.5
      +/- 7.5 ppb after endotoxin and 342.1 +/- 7.2 ppb under control conditions. The
      difference was most pronounced during the first hour after the challenge. We
      conclude that nasal administration of endotoxin causes a short-term increase in
      NO production which must precede cell influx or upregulation of transcription.

PMID- 9262486
TI  - CT guided needle localization for video-thoracoscopic resection of pulmonary
      nodules.
AB  - Because of its decreased invasiveness Video-Assisted Thoracoscopic Surgery (VATS)
      has advantages over the traditional open thoracotomy. However, resection of small
      and subpleural pulmonary nodules via the thoracoscope is often technically
      difficult or impossible. To facilitate the resection of these difficult-to
      palpate lesions, a protocol was established to localize the nodules
      percutaneously with a fine needle under CT guidance. This method was used in four
      patients to localize five lung lesions identified radiographically in various
      lung segments. Of the four patients in the study, three presented with malignancy
      of the lower extremities (alveolar sarcoma, squamous cell carcinoma, and spindle
      cell carcinoma). In two of these patients (having alveolar sarcoma and spindle
      cell carcinoma primaries), the resected pulmonary lesions proved to be metastatic
      disease. The lesions of the other two patients were nonmalignant (actinomycosis
      and fibrotic granuloma). The patients with actinomycosis had two distinct lesions
      which were identified preoperatively with two localizations. All five lesions
      were able to be localized and resected with clear margins. The patients tolerated
      the procedures well without complication. VATS with preoperative CT guided needle
      localization of a subpleural nodule can be a useful diagnostic tool. Its use in
      therapeutic metastasectomy, nonetheless, remains controversial.

PMID- 9262487
TI  - Elevated serum-calcium and parathormone-levels in HIV afflicted female heroin
      addicts.
AB  - Alterations of calcium and bone metabolisms have been observed in numerous
      studies of small groups of male HIV-infected patients. However, our knowledge
      regarding the manifestation of AIDS-associated hypoparathyroidism in female
      subjects is limited. In order to investigate the influence of heroin on the
      calciotropic hormones we performed a cross-sectional study on 45 female patients
      with proven HIV infection. The following criteria were used for exclusion from
      the study: age less than 20/ more than 50 years; confinement to bed; wasting
      symptoms; treatment with agents containing ketoconazole, renal or hepatic
      insufficiency; clinical or echographic signs of liver cirrhosis; endocrine
      diseases, or treatment with drugs known to influence calcium metabolism. A
      reduced parathormone (PTH) level was found among the female HIV-infected
      patients. Additional long-term use of heroin resulted in a significant increase
      of PTH compared to sex- and age matched controls and a second group of non-HIV
      afflicted heroin dependent females. Significantly lowered serum magnesium
      concentrations were found in all three groups. Both serum calcium and urinary
      excretion of calcium were elevated in the group of HIV-infected heroin addicts
      and were independent from low vitamin D3 levels (1,25-dihydroxycholecalciferol)
      and alterations of protein metabolism. Therefore, it is concluded that the
      changes of PTH secretion are mainly due to mechanisms both of the impaired immune
      defense of HIV-infected females and the additional effect of opiates.

PMID- 9262488
TI  - Increased renal natriuretic peptide (urodilatin) excretion in heart failure
      patients.
AB  - Accumulating evidence suggests that urodilatin, a kidney-derived member of the
      natriuretic peptide family, contributes as a major mediator of sodium excretion
      to body fluid regulation in healthy men. In contrast to other members of the
      natriuretic peptide family, pathophysiological data for the renal natriuretic
      peptide have still been missing. The present study compares renal synthesis of
      urodilatin in patients with congestive heart failure (CHF) and healthy
      volunteers. Because urodilatin excretion, considerably increases with increasing
      nutritive sodium intake (p<0.004), the CHF patients (15 NYHA I/II, 8 NYHA III/IV)
      were kept on a 165 mmol/day sodium diet and 6 healthy volunteers on a identical
      nutritive sodium intake level were selected as proper controls. Although
      urodilatin excretion significantly increased (p<0.027) with increasing severity
      of CHF and was therefore significantly higher in mild CHF (40.7 +/- 2.5 fmol/min)
      and severe CHF (54.7 +/- 6.6 fmol/min) than in healthy controls (3.2 +/- 4.2
      fmol/min), both groups of CHF patients retained sodium and had significantly
      lower sodium excretion rates (NYHA I/II 79.0 +/- 6.9 micromol/min, NYHA III/IV
      97.9 +/- 12.7 micromol/min) than the healthy controls (139 +/- 3.4 micromol/min).
      Our data suggest that renal urodilatin synthesis, may not be involved in the
      etiology of sodium retention in CHF, but may rather be stimulated to counteract
      antinatriuresis during CHF.

PMID- 9262489
TI  - Resistance to activated protein C: arterial thrombosis associated with autoimmune
      features.
AB  - A 27 year old woman presented with recurrent cerebrovascular strokes in the
      setting of an ill defined auto-immune disease responsive to corticosteroid
      therapy. Investigation for a hypercoagulable state revealed activated protein C
      resistance in the absence of protein C, protein S, or antithrombin III deficiency
      or anticardiolipin antibodies. Her parents and sibling did not demonstrate APC
      resistance. This case suggests that activated protein C resistance may be
      associated with arterial as well as venous thrombotic events and implies that
      resistance to activated protein C should also be considered in the evaluation of
      young adults with strokes.

PMID- 9262490
TI  - The significance of selected epidemiologico-clinical factors in the prevalence of
      the Helicobacter pylori infection in young males.
AB  - A serological diagnosis (ELISA test) was carried out of infections by
      Helicobacter pylori in 1200 young males (recruits in the Polish Army) and the
      influence of selected epidemiologico-clinical factors (civil status, place of
      residence, profession, economical conditions, tobacco smoking, consumption of
      alcohol, diseases of the parodontonium, nutritional habits) on the prevalence of
      the infection was studied. Specific antibodies were detected in 228 (19%) of the
      persons tested. Of the eight factors analyzed, only three parodontium diseases,
      tobacco smoking and place of residence (of decreasing importance in that order),
      had a statistically significant relationship to infection by Helicobacter pylori
      in young males.

PMID- 9262491
TI  - Clinico-pathological features of colorectal adenomatous polyps with negative
      results on immunochemical fecal occult blood test.
AB  - BACKGROUND: This study was carried out to clarify the clinico-pathological
      features of colorectal adenomatous polyps showing negative results on an
      immunochemical fecal occult blood test. METHODS: Four hundred sixty patients with
      colorectal adenoma 1.0 cm or larger in diameter served as subjects of this study.
      They were divided into two groups based on the results of an immunochemical fecal
      occult blood test with a 3-day method: two hundred twenty four patients with
      positive results (positive group) and two hundred thirty six patients with
      negative results (negative group). The above two groups were compared in terms of
      their individual factors such as lesion site, lesion size, lesion shape, and
      histological type. RESULTS: In negative group, the frequencies of rectal
      adenomatous polyps (p<0.01) and colorectal adenomatous polyps 1.0-1.5 cm in size
      (p<0.001) were higher, and also pedunculated type (p<0.05) were lower than in
      positive group, but there was no difference in histological type between the two
      groups. CONCLUSIONS: These findings suggest that immunochemical fecal occult
      blood testing is relatively inferior for the detection of colorectal adenomatous
      polyps in rectum, smaller size, and non-pedunculated type.

PMID- 9262492
TI  - Candida abscess of the thyroid in a patient with acute lymphocytic leukemia.
AB  - A case of Candida abscess of the thyroid in a patient with acute lymphoblastic
      leukemia is described. The patient developed this rare complication after
      treatment with steroids and combination chemotherapy, during therapy with broad
      spectrum antibiotics for febrile neutropenia. Prior to the thyroiditis the
      patient had pulmonary aspergillosis. The abscess developed during treatment with
      high dose Amphotericin B. Unlike previous cases, the Candida was isolated to the
      thyroid, with no evidence of Candidemia or Candida infection in other sites.

PMID- 9262493
TI  - The acquisition of herpes simplex virus during pregnancy.
AB  - BACKGROUND: The acquisition of genital herpes during pregnancy has been
      associated with spontaneous abortion, prematurity, and congenital and neonatal
      herpes. The frequency of seroconversion, maternal symptoms of the disease, and
      the timing of its greatest effect on the outcome of pregnancy have not been
      systematically studied. METHODS: We studied 7046 pregnant women whom serologic
      tests showed to be at risk for herpes simplex virus (HSV) infection. Serum
      samples obtained at the first prenatal visit, at approximately 16 and 24 weeks,
      and during labor were tested for antibodies to HSV types 1 and 2 (HSV-1 and HSV
      2) by the Western blot assay, and the results were correlated with the occurrence
      of antenatal genital infections. RESULTS: Ninety-four of the women became
      seropositive for HSV; 34 of the 94 women (36 percent) had symptoms consistent
      with herpes infection. Women who were initially seronegative for both HSV-1 and
      HSV-2 had an estimated chance of seroconversion for either virus of 3.7 percent;
      those who were initially seropositive only for HSV-1 had an estimated chance of
      HSV-2 seroconversion of 1.7 percent; and those who were initially HSV-2
      seropositive had an estimated chance of zero for acquiring HSV-1 infection. Among
      the 60 of the 94 pregnancies for which the time of acquisition of HSV infection
      was known, 30 percent of the infections occurred in the first trimester, 30
      percent in the second, and 40 percent in the third. HSV seroconversion completed
      by the time of labor was not associated with an increase in neonatal morbidity or
      with any cases of congenital herpes infection. However, among the infants born to
      nine women who acquired genital HSV infection shortly before labor, neonatal HSV
      infection occurred in four infants, of whom one died. CONCLUSIONS: Two percent or
      more of susceptible women acquire HSV infection during pregnancy. Acquisition of
      infection with seroconversion completed before labor does not appear to affect
      the outcome of pregnancy, but infection acquired near the time of labor is
      associated with neonatal herpes and perinatal morbidity.

PMID- 9262494
TI  - Cumulative effects of high cholesterol levels, high blood pressure, and cigarette
      smoking on carotid stenosis.
AB  - BACKGROUND: Single measurements of cardiovascular risk factors may not accurately
      reflect a person's past exposure to those risk factors. We therefore studied the
      long-term associations of cardiovascular risk factors such as high serum
      cholesterol levels, high blood pressure, and cigarette smoking with the
      prevalence of carotid stenosis. METHODS: We studied cross-sectional and
      longitudinal information from a sample of 429 men and 661 women in the Framingham
      Heart Study who underwent B-mode ultrasound measurements of the carotid artery.
      Their mean age was 75 years, and each had attended most of the biennial clinic
      examinations over the 34 years before the carotid ultrasound study. We used time
      integrated measurements to assess the associations between various cardiovascular
      risk factors and the degree of carotid stenosis. RESULTS: Moderate carotid
      stenosis (> or =25 percent) was present in 189 men and 226 women. We assessed the
      odds ratios for this degree of stenosis as compared with minimal stenosis (<25
      percent) according to increases in risk factors. In the men, the odds ratio for
      moderate carotid stenosis associated with an increase of 20 mm Hg in systolic
      blood pressure was 2.11 (95 percent confidence interval, 1.51 to 2.97). The odds
      ratio for an increase of 10 mg per deciliter (0.26 mmol per liter) in the
      cholesterol level was 1.10 (95 percent confidence interval, 1.03 to 1.16), and
      for an increase of five pack-years of smoking it was 1.08 (95 percent confidence
      interval, 1.03 to 1.13). The results were similar in the women. Time-integrated
      measurements of diastolic blood pressure showed significant associations with
      carotid stenosis in men and insignificant associations in women. CONCLUSIONS:
      Over the long term, high systolic blood pressure, high cholesterol levels, and
      smoking were associated with an increased risk of carotid stenosis in this
      elderly population.

PMID- 9262495
TI  - The effect of calcium supplementation on bone density during lactation and after
      weaning.
AB  - BACKGROUND: Women may lose bone during lactation because of calcium lost in
      breast milk. We studied whether calcium supplementation prevents bone loss during
      lactation or augments bone gain after weaning. METHODS: We conducted two
      randomized, placebo-controlled trials of calcium supplementation (1 g per day) in
      postpartum women. In one trial (the study of lactation), 97 lactating and 99
      nonlactating women were enrolled a mean (+/-SD) of 16+/-2 days post partum. In
      the second trial (the study of weaning), 95 lactating women who weaned their
      infants in the 2 months after enrollment and 92 nonlactating women were enrolled
      5.6+/-0.8 months post partum. The bone density of the total body, lumbar spine,
      and forearm was measured at enrollment and after three and six months. RESULTS:
      The bone density of the lumbar spine decreased by 4.2 percent in the lactating
      women receiving calcium and by 4.9 percent in those receiving placebo and
      increased by 2.2 and 0.4 percent, respectively, in the nonlactating women
      (P<0.001 for the effect of lactation; P= 0.01 for the effect of calcium). After
      weaning, the bone density of the lumbar spine increased by 5.9 percent in the
      lactating women receiving calcium and by 4.4 percent in those receiving placebo;
      it increased by 2.5 and 1.6 percent, respectively, in the nonlactating women
      (P<0.001 for the effects of lactation and calcium). There was no effect of either
      lactation or calcium supplementation on bone density in the forearm, and there
      was no effect of calcium supplementation on the calcium concentration in breast
      milk. CONCLUSIONS: Calcium supplementation does not prevent bone loss during
      lactation and only slightly enhances the gain in bone density after weaning.

PMID- 9262496
TI  - Mutations of the p53 gene as a prognostic factor in aggressive B-cell lymphoma.
AB  - BACKGROUND: Mutations of the p53 gene are associated with a poor prognosis in
      several types of cancer. We investigated the prognostic importance of p53
      mutations in patients with aggressive B-cell lymphoma. METHODS: We examined the
      relation between the presence or absence of a detectable p53 mutation in lymphoma
      cells and the response to chemotherapy and overall survival in 102 previously
      untreated patients with aggressive B-cell lymphoma. Mutations of the p53 gene
      were identified by polymerase-chain-reaction-mediated analysis of single-strand
      conformation polymorphisms and by direct sequencing. RESULTS: Of 102 cases of
      aggressive B-cell lymphoma, 22 (22 percent) involved p53 mutations. The rate of
      complete remission was significantly lower in patients with a tumor carrying a
      p53 mutation (6 of 22 patients, 27 percent) than in those with the wild-type p53
      gene (61 of 80 patients, 76 percent) (P<0.001). Overall survival was
      significantly lower among patients with p53 mutations than among those with the
      wild-type p53 gene; the Kaplan-Meier estimates of survival at five years were 16
      percent and 64 percent, respectively (P<0.001). Multivariate analysis
      incorporating prognostic factors from the international prognostic index
      demonstrated that p53 mutations had independent effects on the rates of complete
      remission and survival. When we categorized patients according to the
      international prognostic index, we found no effect of p53 mutations in patients
      in the groups at high-intermediate and high risk. However, these mutations were
      significantly associated (P< 0.001) with low rates of complete remission (33
      percent vs. 91 percent) and survival (27 percent vs. 81 percent at five years) in
      the groups at low and low-intermediate risk. CONCLUSIONS: Mutations of the p53
      gene are associated with a poor prognosis in patients with aggressive B-cell
      lymphoma.

PMID- 9262497
TI  - Images in clinical medicine. Positive Tzanck smear.

PMID- 9262498
TI  - Discrepancies between meta-analyses and subsequent large randomized, controlled
      trials.
AB  - BACKGROUND: Meta-analyses are now widely used to provide evidence to support
      clinical strategies. However, large randomized, controlled trials are considered
      the gold standard in evaluating the efficacy of clinical interventions. METHODS:
      We compared the results of large randomized, controlled trials (involving 1000
      patients or more) that were published in four journals (the New England Journal
      of Medicine, the Lancet, the Annals of Internal Medicine, and the Journal of the
      American Medical Association) with the results of meta-analyses published earlier
      on the same topics. Regarding the principal and secondary outcomes, we judged
      whether the findings of the randomized trials agreed with those of the
      corresponding meta-analyses, and we determined whether the study results were
      positive (indicating that treatment improved the outcome) or negative (indicating
      that the outcome with treatment was the same or worse than without it) at the
      conventional level of statistical significance (P<0.05). RESULTS: We identified
      12 large randomized, controlled trials and 19 meta-analyses addressing the same
      questions. For a total of 40 primary and secondary outcomes, agreement between
      the meta-analyses and the large clinical trials was only fair (kappa= 0.35; 95
      percent confidence interval, 0.06 to 0.64). The positive predictive value of the
      meta-analyses was 68 percent, and the negative predictive value 67 percent.
      However, the difference in point estimates between the randomized trials and the
      meta-analyses was statistically significant for only 5 of the 40 comparisons (12
      percent). Furthermore, in each case of disagreement a statistically significant
      effect of treatment was found by one method, whereas no statistically significant
      effect was found by the other. CONCLUSIONS: The outcomes of the 12 large
      randomized, controlled trials that we studied were not predicted accurately 35
      percent of the time by the meta-analyses published previously on the same topics.

PMID- 9262499
TI  - Injury prevention. First of two parts.

PMID- 9262500
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 26-1997. A 64-year-old man with progressive dementia, seizures,
      and unstable gait.

PMID- 9262501
TI  - Calcium supplementation during breast-feeding.

PMID- 9262502
TI  - The promise and problems of meta-analysis.

PMID- 9262503
TI  - Should a low-fat, high-carbohydrate diet be recommended for everyone? The case
      for a low-fat, high-carbohydrate diet.

PMID- 9262504
TI  - Should a low-fat, high-carbohydrate diet be recommended for everyone? Beyond low
      fat diets.

PMID- 9262505
TI  - Age-associated decline in human femoral neck cortical and trabecular content of
      insulin-like growth factor I: potential implications for age-related (type II)
      osteoporotic fracture occurrence.
AB  - Recent evidence suggests that regulatory peptides such as insulin-like growth
      factor-I (IGF-I) are released locally from bone during resorption, and may then
      act in a sequential manner to regulate the cellular events required for the
      coupling of bone formation to resorption. Among other factors, a decrease in bone
      associated IGF-I levels could therefore result in remodeling imbalance and
      contribute to the gradual loss of bone that occurs with age. As the femoral neck
      region is of primary concern for the clinical manifestations of osteoporosis, the
      current study was intended to assess the IGF-I contents in femoral neck cortical
      and trabecular bone from aging individuals. Bone samples from the neck region
      were obtained at postmortem from 39 females and 35 males, aged 23-92 years.
      Concentrations of IGF-I and osteocalcin were measured by radioimmunoassay in the
      supernatants obtained after EDTA and guanidine hydrochloride extraction. The
      total amount of protein present in the extracts was determined by
      spectrophotometry. IGF-I levels were significantly lower in trabecular compared
      with cortical bone. Though femoral neck total protein did not vary with donor
      age, both IGF-I and osteocalcin were found to decline markedly. Between the ages
      of 23 and 92 years, average yearly rates of loss of 0.30 and 0.21 ng IGF-I/mg
      protein were observed in cortical and trabecular bone, respectively,
      corresponding with net losses of nearly 35% of the cortical skeletal content of
      IGF-I and 41% of the trabecular skeletal content of IGF-I. These changes in bone
      associated IGF-I paralleled those of osteocalcin, consistent with an overall
      decrease in osteoblast function with aging. In women, the rate of decline was
      significantly faster for trabecular than for cortical IGF-I, however in men, age
      dependent changes in cortical and trabecular IGF-I were similar. These findings
      support the hypothesis that changes in the local IGF regulatory system over time
      could be a pathophysiologic component of the age-related (type II) femoral neck
      osteoporotic syndrome.

PMID- 9262506
TI  - Calcification of the lumbar vertebrae during human fetal development.
AB  - The calcification rate of the human fetal vertebrae has not been previously
      documented. In bridging this gap in knowledge, this report will specifically
      provide reference values for mineral content in predominantly trabecular bone
      during its formation in the prenatal period. Such information would facilitate
      early detection of ossification defects which become apparent in the fetal spine
      as early as 20 weeks of gestation [1]. Lumbar vertebrae were obtained at autopsy
      from 33 human fetuses aged 17-41 weeks of gestation. Vertebral demineralization
      was effected using an acid-alcohol solution. The extracted concentrations of
      calcium and phosphorus were determined spectrometrically from the solutions.
      Atomic absorption spectroscopy was used to determine calcium concentration and
      phosphate concentration was assessed by ultraviolet colorimetry. Mineralization
      could be described by a linear relationship over the age range studied. Calcium
      was taken up by the fetal vertebrae at twice the rate of phosphorus (0.2% per
      week). When the fetuses were classed according to similar gestational ages, the
      Ca/P weight ratios increased from 1.7 in the youngest group to 2.2 in the oldest
      group. The time of onset of calcification, calculated by extrapolation of the
      calcium data, appeared to be earlier than ultrastructural studies by other
      investigators suggest, but was subject to many uncertainties.

PMID- 9262507
TI  - Expression of bone sialoprotein in human lung cancer.
AB  - Lung cancer belongs to the group of malignant lesions that specifically select
      bone as secondary implantation site. The molecular bases for this property,
      defined as osteotropism, is still largely unknown. The recent demonstration that
      human breast cancer cells express and attach to bone sialoprotein (BSP), a
      sulfated phosphoprotein rich in bone and other mineralized tissues, could provide
      a clue to elucidating bone metastases formation. BSP contains the integrin
      binding peptide Arg-Gly-Asp (RGD), as well as non-RGD cell attachment domain.
      Using an immunoperoxidase technique and a specific polyclonal antibody directed
      against a BSP synthetic peptide, we examined the expression of BSP in 48 lung
      lesions including 25 squamous carcinoma, 21 adenocarcinoma, and 2
      bronchioloalveolar cancers, as well as 38 human ovarian carcinoma that constitute
      a group of generally nonosteotropic cancers. BSP was not specifically detected in
      normal lung tissue with the exception of cartilage associated with bronchi. Most
      of the adenocarcinoma (74%) and all squamous carcinoma of the lung examined
      exhibited detectable levels of BSP. Staining was mainly cytoplasmic and membrane
      associated. The two bronchioloalveolar lung cancers examined did not show
      detectable amounts of BSP. When microcalcifications were observed in pulmonary
      malignant lesions, they were usually associated with cancer cells expressing BSP.
      Only 21% of the ovarian cancers examined contained malignant cells with 2+ or 3+
      positivity for BSP. We further demonstrated that in 8 of 10 additional lung
      cancers, BSP was detected at the mRNA level. Our observation is the first
      demonstration that BSP is expressed in non-small cell lung carcinoma. Lung cancer
      cells are now the second type of osteotropic malignant cells described to express
      BSP. Added to the observation that BSP expression is not frequent in ovarian
      carcinoma, a low osteotropic cancer, our study supports our hypothesis that BSP
      could play a role in determining the affinity of cancer cells to bone.

PMID- 9262508
TI  - Symmetry of bone mineral density at the proximal femur with emphasis on the
      effect of side dominance.
AB  - The symmetry and effect of side dominance on the bone mineral density (BMD) of
      proximal femur was evaluated in 266 normal Chinese women with a dual photon
      absorptiometer (DPA, Norland 2600). The BMDs of the femoral neck, trochanter, and
      Ward's triangle at the proximal femur in the dominant leg (BMDd) were compared
      with those of the nondominant side (BMDn). The linear regression of BMDd and BMDn
      of the corresponding regions at the proximal femur showed a good correlation (r =
      0.893-0.941, SEE = 0.052-0.062 g/cm2). The paired difference of proximal femoral
      BMD was -0.002 +/- 0.062 g/cm2 for the femoral neck, 0.003 +/- 0.054 g/cm2 for
      the trochanter, and 0.008 +/- 0.062 g/cm2 for the Ward's triangle. The ratio of
      asymmetry for femoral neck BMD was mean +/- SD = -0.4 +/- 7.8%, for trochanter
      0.6 +/- 8.1%, and for the Ward's triangle 1.3 +/- 9.7%. Both paired difference
      and ratio of asymmetry between BMDd and BMDn were approximately normally
      distributed, with a mean +/- 2 SD ranging from -0.126 to 0.122 g/cm2 for paired
      difference and -16.0% to 15.2% for the ratio of asymmetry in the femoral neck.
      These data revealed that dominance had little effect on the proximal femur BMDs.
      However, the wide range of paired difference and ratio of asymmetry of the
      proximal femur BMD in the normal individuals should be considered in the
      interpretation of the proximal femoral BMD.

PMID- 9262509
TI  - Bone metabolism during exercise and recovery: the influence of plasma volume and
      physical fitness.
AB  - Understanding the reaction of bone to physical exercise is important for the
      development of strategies to increase and maintain bone mass. In this study the
      aim was to investigate the relationship among exercise intensity, physical
      capacity, and the biochemical responses, estimated by measuring biochemical
      markers of bone metabolism in serum. As a complement to the circulating
      concentrations we also accounted for the plasma volume shifts during and after
      exercise. The study included 10 men and 10 women, mean age 29 years, with a wide
      range of physical capacity, who performed a standardized running exercise test on
      a motor-driven treadmill with loads corresponding to 47 and 76% of VO2 max
      (maximal oxygen uptake) followed by a maximal effort until exhaustion. Total work
      time was about 35 minutes. Venous blood samples were drawn at rest, after each
      load, and after 30 minutes and 24 hours of recovery. The reductions in plasma
      volume during exercise were 4.3% (P < 0.05) and 15.1% (P < 0.001) whereas after
      24 hours in recovery there was an expansion of 7.5% (P < 0.001). There were
      marked, intensity-related, increases of PICP and tALP concentrations (P < 0.001)
      during exercise. Since these were of the order of plasma volume reduction they
      did not correspond to a change in the calculated circulating amount (content).
      However, as the concentrations returned to basal during recovery, the total
      circulating amounts were increased at this point (P < 0.05). Osteocalcin was also
      increased during recovery (P < 0.01), although concentrations were unchanged
      during the entire study. The amount (P < 0.001) and concentration (P < 0. 05) of
      ICTP were also increased during follow-up. Serum PTH concentrations rose (P <
      0.05) in proportion to the intensity of exercise and remained elevated during
      recovery. The subjects' VO2 max demonstrated positive relationships to the
      biochemical responses to exercise in bone and BMD of the legs, and a negative
      relationship to basal PTH levels. Bone turnover and PTH secretion was stimulated
      by exercise, and low basal levels of PTH and high BMD were induced by a high
      level of physical fitness. These observations correlate well with the favorable
      effects of exercise and training on bone mass.

PMID- 9262510
TI  - Expression of p21CIP1/WAF1 in chondrocytes.
AB  - During endochondral ossification, proliferative activity of chondrocytes is
      arrested and the cells undergo terminal hypertrophic differentiation. We examined
      the expression of the cyclin-dependent kinase inhibitor, p21(CIP1/WAF1) in
      permanent cartilage (xyphoid and articular cartilage) and in cartilage undergoing
      endochondral ossification (growth plate, epiphyseal ossification centers, and
      costochondral junctions) to determine if p21 is up-regulated in chondrocytes
      during hypertrophic differentiation. Northern blot analyses demonstrated
      expression of p21 in chondrocytes undergoing endochondral ossification and from
      sites of permanent cartilage. Quantitative analyses of Northern data showed an
      association between expression of the hypertrophic-specific marker, collagen type
      X, and the level of 21 expression. In situ hybridization of rodent femoropatellar
      joints and costochondral junctions localized p21 mRNA to chondrocytes within both
      the proliferative and hypertrophic zones of the growth plates, in chondrocytes
      involved in formation of the epiphyseal ossification centers, and in articular
      chondrocytes. Immunohistochemical analyses of p21 expression in the same tissues
      demonstrated comparatively higher levels of p21 protein in postmitotic
      chondrocytes. These data suggest that p21 is active in cell cycle regulation in
      chondrocytes, and that increased p21 expression is associated with hypertrophic
      differentiation.

PMID- 9262511
TI  - c-fms mRNA is regulated posttranscriptionally by 1,25(OH)2D3 in HL-60 cells.
AB  - Macrophage colony-stimulating factor (MCSF) is required for normal osteoclast and
      macrophage development. The receptor for MCSF (c-fms) is expressed on the
      pluripotent precursor and mature osteoclasts and macrophages. We have previously
      shown in myelomonocytic HL-60 cells that phorbol myristate acetate (PMA)
      upregulates c-fms mRNA expression. This induction of c-fms is inhibited by
      1,25(OH)2D3. The major regulatory control of c-fms mRNA levels by PMA has been
      identified as posttranscriptional. However, a role of transcript elongation in
      controlling levels of c-fms mRNA has also been suggested. To better understand
      the 1,25(OH)2D3 regulation of c-fms mRNA expression we studied nuclear run on,
      mRNA stability, and transcript elongation in HL-60 cells treated with 10 ng/ml
      phorbol myristate acetate, 10 nM 1,25(OH)2D3 alone or combined. We demonstrated
      by nuclear run on that c-fms was constitutively transcribed in 1,25(OH)2D3 as
      well as control and PMA-treated cells. Transcript elongation was evaluated by RT
      PCR for exon 2 or exon 3. Both exons were minimally expressed in control and
      1,25(OH)2D3-treated cells, and increased in PMA-treated cells; this increased
      expression was inhibited by the addition of 1,25(OH)2D3. These results fail to
      show differential transcript elongation. Measurement of mRNA stability
      demonstrated decreased mRNA half-life to 5 hours in cells treated with PMA and
      1,25(OH)2D3 compared with a half-life of 8 hours in cells treated with PMA alone.
      Our findings demonstrate that c-fms is regulated by 1,25(OH)2D3 at the
      posttranscriptional level by changes in mRNA stability. This gives the cell the
      ability to respond to local signals with rapid changes in c-fms levels altering
      the ability of the cell to respond to MCSF.

PMID- 9262512
TI  - Chicken parathyroid hormone gene expression in response to gastrin, omeprazole,
      ergocalciferol, and restricted food intake.
AB  - Treatment with omeprazole, a long-acting proton pump inhibitor of acid secretion,
      induces hypergastrinemia. In chickens, omeprazole induces growth not only of the
      acid-producing mucosa (probably reflecting the trophic action of gastrin), but
      also of the parathyroid glands (hypertrophy + hyperplasia), while suppressing
      bone density and body weight gain without affecting blood calcium. The first part
      of the present study was concerned with the effect of omeprazole, ergocalciferol
      (vitamin D2), and restricted food intake on the gene expression of parathyroid
      hormone (PTH) in the parathyroid glands of the chicken. Chickens were treated
      with omeprazole (400 micromol/kg/day, I.M.), food restriction, omeprazole + food
      restriction, ergocalciferol (250 000 IU/kg/day, S.C.), or ergocalciferol +
      omeprazole for 5 weeks. The weight gain of the chickens was monitored, and the
      weights of the parathyroid glands and femurs were determined at sacrifice. PTH
      mRNA in the parathyroid glands was analyzed by Northern blot. The second part of
      the study examined the effect of 3 weeks of continuous gastrin infusion (chicken
      gastrin 20-36, 5 nmol/kg/hour, S.C.) on the expression of PTH mRNA in the
      parathyroid glands. Omeprazole reduced the body weight and femur density (ash
      weight per volume) while greatly increasing the weight of the parathyroid glands
      and the PTH gene expression. Food restriction alone and ergocalciferol alone (at
      a dose that raised blood Ca2+) were without effect, but food restriction greatly
      enhanced the omeprazole-evoked increase in parathyroid gland weight and PTH gene
      expression. Gastrin increased the weight of the parathyroid glands and reproduced
      the effect of omeprazole on PTH gene expression. Hence, it seems likely that the
      effect of omeprazole reflects the ensuing hypergastrinemia.

PMID- 9262513
TI  - Crystal growth and molecular modeling studies of inhibition of struvite by
      phosphocitrate.
AB  - The inhibition by phosphocitrate of struvite crystal formation and growth has
      been examined in the present study. Crystal growth in a gel matrix was controlled
      by phosphocitrate in a dose-dependent manner. The effects of inhibition were
      followed using scanning electron microscopy, optical microscopy, and single
      crystal X-ray analysis. The presence of phosphocitrate induced very strong,
      crystal face specific inhibition of struvite, leading to total cessation of
      crystal growth when sufficient concentration of the inhibitor was made available.
      Crystal growth studies and results from molecular modeling indicated strong
      affinity of phosphocitrate to (101) faces of struvite. This in turn led to an
      alteration in the expression of these faces and the development of a
      characteristic arrowhead struvite morphology. Similar changes were not observed
      in the presence of identical concentrations of citrate, acetohydroxamic acid, and
      N-sulfo-2 amino tricarballylate (an analog of phosphocitrate), emphasizing the
      unique interaction of phosphocitrate with the struvite crystal lattice.

PMID- 9262514
TI  - Estimation of total collagen and types I and III collagen in canine rotator cuff
      tendons.
AB  - The collagen composition of the supraspinatus, infraspinatus, and subscapularis
      tendons, which form part of the rotator cuff of the shoulder, was determined.
      Tendons were obtained from adult, male beagle dogs and total collagen was
      estimated by measurement of hydroxyproline. There was little variation in
      collagen content among the three major cuff tendons and the quantity approximated
      that cited in the literature for other tendons. However, the collagen content in
      the insertion zone of the supraspinatus tendon was significantly higher than in
      the tendon proper. NaCl fractionation of supraspinatus collagen indicated that
      type I was the predominant collagen but significant amounts of type III and
      possibly some type II and type V were also present. Interestingly, there appeared
      to be more type III collagen in the insertion zone than in the tendon proper,
      cyanogen bromide digestion and peptide mapping confirmed this finding. The
      differential collagen composition of the supraspinatus tendon may contribute to
      the high incidence of tear that is associated with this rotator cuff tendon.

PMID- 9262515
TI  - Effects of magnesium deficiency on magnesium and calcium content in bone and
      cartilage in developing rats in correlation to chondrotoxicity.
AB  - Quinolone-induced arthropathy has been described in juvenile rats between 3 and 6
      weeks of age, but not in adult rats. The mechanism of this chondrotoxic effect is
      probably related to the Mg2+-chelating properties of the drugs, since identical
      cartilage lesions were observed in magnesium-deficient juvenile rats without
      quinolone treatment. However, the reasons for the phase-specificity of the effect
      are unknown. In the present study, we fed a magnesium-deficient diet to Wistar
      rats at different postnatal developmental stages. Cartilage lesions were only
      observed in magnesium-deficient rats between 3 and 5 weeks of age, but not in
      rats receiving the magnesium-deficient diet during weeks 5 to 8, weeks 8 to 11,
      or months 15 to 16. The formation of cartilage lesions was not related to the
      magnesium concentration in plasma, since magnesium concentrations in plasma were
      similarly reduced in rats with and without cartilage lesions. However,
      chondrotoxicity correlated with magnesium content in articular cartilage. In
      articular cartilage (articular and epiphyseal cartilage in immature rats) and
      bone, magnesium content was more reduced in rats receiving the magnesium
      deficient diet between 3 and 5 weeks of age as compared with rats receiving the
      magnesium-deficient diet during weeks 8 to 11 postnatally. It was not possible to
      reduce the magnesium content in bone tissue of 15-month-old Wistar rats, which
      suggests a lower magnesium turnover in aged rats. Magnesium content in epiphyseal
      cartilage of 2-week-old rats (total femoral head) was 41.9 +/- 16.9 mmol/kg dry
      weight. The magnesium content in joint hyaline cartilage was significantly lower
      in 4-week-old rats (19.5 +/- 3.6 mmol/kg dry weight) and increased subsequently
      again to 48.5 +/- 9.2 mmol/kg dry weight (mean +/- SD; n = 8 to 16). Increase of
      the magnesium content in femoral bone between weeks 4 and 6 postnatally was less
      pronounced (139 +/- 10 and 175 +/- 15 mmol/kg dry weight, respectively). Taken
      together, these data show that in 4-week-old rats, magnesium concentration in
      joint hyaline cartilage is significantly lower than at other times during
      postnatal development. Only at this developmental stage can cartilage lesions be
      induced by feeding rats a magnesium-deficient diet. This period correlates well
      with the sensitive phase of immature rats toward the chondrotoxic action of
      quinolones.

PMID- 9262516
TI  - Preventive effects of traditional Chinese (Kampo) medicines on experimental
      osteoporosis induced by ovariectomy in rats.
AB  - Preventive effects by traditional Chinese (Kampo) medicines, Unkei-to, Hachimi
      jio-gan, and Juzen-taiho-to, on the progress of bone loss induced by ovariectomy
      in rats were investigated for a period of 49 days. The bone mineral density (BMD)
      of tibia in ovariectomized (OVX) rats decreased by 20% from those in sham
      operated (Sham) rats, with the decrease completely inhibited by the
      administration of any one of these Kampo medicines or 17beta-estradiol. From
      scanning electron microscopic (SEM) analyses, the surface of a trabecular bone of
      tibia in OVX rats had a porous or erosive appearance, whereas that of the same
      bone in Sham rats was composed of fine particles. The administration of three
      Kampo medicines and 17beta-estradiol to OVX rats preserved the fine particle
      surface of the trabecular bone. These results strongly suggest that any of these
      three gynecological Kampo medicines is as effective as 17beta-estradiol in
      preventing the development of bone loss induced by ovariectomy in rats.

PMID- 9262517
TI  - Evidence for the involvement of carbonic anhydrase and urease in calcium
      carbonate formation in the gravity-sensing organ of Aplysia californica.
AB  - To better understand the mechanisms that could modulate the formation of
      otoconia, calcium carbonate granules in the inner ear of vertebrate species, we
      examined statoconia formation in the gravity-sensing organ, the statocyst, of the
      gastropod mollusk Aplysia californica using an in vitro organ culture model. We
      determined the type of calcium carbonate present in the statoconia and
      investigated the role of carbonic anhydrase (CA) and urease in regulating
      statocyst pH as well as the role of protein synthesis and urease in statoconia
      production and homeostasis in vitro. The type of mineral present in statoconia
      was found to be aragonitic calcium carbonate. When the CA inhibitor,
      acetazolamide (AZ), was added to cultures of statocysts, the pH initially (30
      min) increased and then decreased. The urease inhibitor, acetohydroxamic acid
      (AHA), decreased statocyst pH. Simultaneous addition of AZ and AHA caused a
      decrease in pH. Inhibition of urease activity also reduced total statoconia
      number, but had no effect on statoconia volume. Inhibition of protein synthesis
      reduced statoconia production and increased statoconia volume. In a previous
      study, inhibition of CA was shown to decrease statoconia production. Taken
      together, these data show that urease and CA play a role in regulating statocyst
      pH and the formation and maintenance of statoconia. CA produces carbonate ion for
      calcium carbonate formation and urease neutralizes the acid formed due to CA
      action, by production of ammonia.

PMID- 9262518
TI  - Skeletal casein kinase activity defect in the HYP mouse.
AB  - The Hyp mouse, a model for human X-linked hypophosphatemia (XLH), is
      characterized by phosphate wasting and defective mineralization. Since
      osteopontin (OPN) is considered pivotal for biological mineralization, we
      examined the biosynthesis of OPN in osteoblasts of +/Y and Hyp/Y mice.
      Immunoprecipitation analyses using a specific antibody to OPN revealed that Hyp/Y
      and +/Y osteoblasts secrete similar levels of OPN as determined by [35S]
      methionine biosynthetic labeling, but a reduced phosphorylation was noted after
      32P-PO4 biosynthetic labeling. Northern blot hybridization analysis of +/Y and
      Hyp/Y mice osteoblast mRNAs, using a cDNA probe for mouse OPN, revealed no
      difference in the steady state levels of osteopontin mRNA. Analysis of casein
      kinase II activity in +/Y and Hyp/Y mice osteoblast, kidney, heart and liver
      membrane fractions revealed that casein kinase II activity in the Hyp/Y mice
      osteoblasts and kidney is only 35%-50%, respectively, of that of the +/Y mice
      tissues. The accumulated data are consistent with a post-translation defect in
      the Hyp/Y mouse osteoblast which results in the under-phosphorylation of
      osteopontin and subsequent under-mineralization of bone matrix.

PMID- 9262519
TI  - Goal-directed therapy for erectile dysfunction.

PMID- 9262520
TI  - Epstein-Barr virus infection in infants and their mothers.

PMID- 9262521
TI  - Emergency medicine and family physicians.

PMID- 9262522
TI  - Emergency medicine and family physicians.

PMID- 9262523
TI  - New models of health care in the home and in the work site.

PMID- 9262524
TI  - Recognition and management of Lyme disease.
AB  - Lyme disease, the most common tick-borne illness in the United States, has an
      annual incidence of 0.5 percent in endemic areas. It most commonly occurs in the
      Northeast and upper Midwest, in areas that encourage and harbor the deer tick.
      The tick transmits an infection of the spirochete Borrelia burgdorferi that
      typically manifests as a localized skin lesion, erythema migrans. Rarely, Lyme
      disease manifests as localized arthritis, heart block or disease of the nervous
      system. Lyme disease is a clinical diagnosis, and laboratory tests should only be
      used to clarify diagnostic issues. The current standard for laboratory diagnosis
      includes a two-step approach using an initial immunoassay with a confirmatory
      Western blot. Treatment includes 10 to 21 days of oral doxycycline in nonpregnant
      adults or a similar course of amoxicillin in children or pregnant women.
      Overdiagnosis and overtreatment of Lyme disease have become common.

PMID- 9262525
TI  - Dermatoses in newborns.
AB  - Benign dermatoses in newborns must be distinguished from more serious disorders
      with cutaneous manifestations. Erythema toxicum neonatorum, transient neonatal
      pustular melanosis, sucking blister, miliaria and mongolian spots are among the
      many benign skin conditions that can occur in newborns. Recognition of these
      dermatoses allows the physician to proceed appropriately, reassure the parents
      and initiate further evaluation or treatment as necessary. To avoid adverse
      sequelae, special attention must be given to more persistent conditions and those
      with the potential for complications or malignant transformation. Consultation
      with a pediatric dermatologist, a plastic surgeon or a neurosurgeon may be
      necessary.

PMID- 9262526
TI  - Antidepressant withdrawal reactions.
AB  - Antidepressants can cause a variety of withdrawal reactions, starting within a
      few days to a few weeks of ceasing the drug and persisting for days to weeks.
      Both tricyclic antidepressants and selective serotonin reuptake inhibitors cause
      similar syndromes, most commonly characterized by gastrointestinal or somatic
      distress, sleep disturbances, mood fluctuations and movement disorders. Most
      symptoms related to tricyclic antidepressant withdrawal are believed to be caused
      by rebound excess of cholinergic activity after prolonged anticholinergic effect
      on cholinergic receptors. (This situation is analogous to the adrenergic rebound
      that occurs after beta-blocker withdrawal.) Treatment involves restarting the
      antidepressant and tapering it more slowly. Alternatively, tricyclic
      antidepressant withdrawal symptoms often respond to anticholinergics, such as
      atropine or benztropine mesylate. Three case reports of antidepressant withdrawal
      are presented, including one featuring akathisia (motor restlessness) related to
      withdrawal of venlafaxine.

PMID- 9262527
TI  - Intrathecal narcotics for labor analgesia.
AB  - Intrathecal narcotics are a relatively recent addition to the list of analgesic
      options that are available for the management of labor pain. Pain during the
      first stage of labor is related to repetitive uterine contractions and resultant
      cervical dilatation, while pain during the second stage is due to stretching of
      the perineum. Traditionally, continuous epidural analgesia has been used as the
      reference standard for providing comfort during labor. Intrathecal narcotics
      represent a safe and effective alternative that provides significant, rapid
      relief of labor pain during the first stage of labor. The drugs most often used
      for intrathecal administration include sufentanil, fentanyl, meperidine and
      morphine. Use of intrathecal narcotics does not significantly affect the natural
      progression of labor, and no adverse fetal outcomes have been reported.

PMID- 9262528
TI  - Reducing the complications of type II diabetes: a patient-centered approach.
AB  - Diabetes mellitus is responsible for 12 percent of health care expenditures in
      the United States, and much of the cost can be attributed to the treatment of
      complications. Morbidity, particularly the development of microvascular
      complications, has been linked to poor glycemic control in type 1 diabetes.
      Evidence strongly suggests that improved glycemic control may reduce the
      morbidity, mortality and treatment costs of type II diabetes. To prevent
      cardiovascular complications, physicians and patients must work together to
      address risk factors such as dyslipidemia, hypertension and smoking. Effective
      care of type II diabetes requires an appropriate diet, an exercise program and,
      if needed, a carefully monitored drug regimen. In addition, physicians and
      patients need to cooperate in setting goals and making tradeoffs related to the
      potential benefits and adverse effects of therapy. Individualized patient
      education and support groups also can be very useful.

PMID- 9262529
TI  - Primary care of adults with mental retardation living in the community.
AB  - An increased number of adults with mental retardation are living in the community
      and seeking health care from family physicians. When mentally retarded patients
      are enrolled in a medical practice, guardianship status should be determined, but
      these patients should be involved in their own care to as great an extent
      possible. Since a verbal history may be difficult to obtain, a systematic,
      thorough physical examination is important. Certain Illnesses, such as hepatitis
      B, recurrent aspiration syndrome, leukemia and atlantoaxial instability, are much
      more common in adults with Down syndrome then in adults with mental retardation
      from other causes. Seizures and mental illness are equally common in all mentally
      retarded adults. The behavior management and pharmacologic therapy of patients
      with mental retardation are best handled in close association with caregivers, as
      well as psychiatrists and neurologists who are familiar with the special needs of
      this population.

PMID- 9262530
TI  - The serum digoxin concentration: ten questions to ask.
AB  - Although the role of digoxin therapy has been the subject of debate, the drug is
      generally accepted as effective in the treatment of heart failure due to systolic
      dysfunction and as therapy for atrial fibrillation and supraventricular
      tachyarrhythmias. Serum digoxin concentrations are commonly used to gauge patient
      response to digoxin. Digoxin pharmacokinetics are complex, and many factors can
      confound the interpretation of digoxin concentrations. The exact therapeutic
      range of serum digoxin varies in the literature but should be considered to be
      from 0.8 to 2.0 ng per mL, on the basis of population data regarding therapeutic
      response and toxicity. Renal function plays a major role in digoxin
      pharmacokinetics and is an important factor in determining digoxin doses. Many
      medications, including quinidine, amiodarone and verapamil, alter digoxin
      pharmacokinetics and can result in two- to three-fold increases in the serum
      digoxin concentration. Effective interpretation of the digoxin concentration
      requires consideration of the patient's renal function and clinical status,
      possible drug interactions, time of the assay and other variables.

PMID- 9262531
TI  - Diagnostic imaging in the evaluation of constipation in adults.
AB  - Acute and chronic constipation are common conditions. In most instances, a
      thorough history and digital rectal examination provide sufficient information to
      begin treatment. Occasionally, imaging studies can be useful to confirm the
      presence of a suspected abnormality. The acute onset of constipation suggests
      colonic obstruction. Plain abdominal radiographs may be sufficient to determine
      the level and cause of the obstruction, such as sigmoid or cecal volvulus. Barium
      enema radiographic examination or colonoscopy may also be useful to detect the
      cause of obstruction. In patients with chronic constipation, plain abdominal
      radiographs can be used to show the extent of fecal impaction. Colonic transit
      time can be assessed on serial abdominal radiographs after the patient has
      ingested radiopaque markers. Evacuation proctography can be used to diagnose a
      variety of functional disorders of the rectum and anus, such as rectocele,
      intussusception and abnormal perineum floor descent.

PMID- 9262532
TI  - Hepatic hydrothorax: possible etiology of recurring pleural effusion.
AB  - A case of hepatic hydrothorax is presented as a reminder that a large, recurring
      pleural effusion may have an abdominal source, even in patients with minimal or
      no apparent ascites. One of the known mechanisms for hepatic hydrothorax is a
      peritoneopleural communication, as demonstrated in this case. A simple
      radionuclide imaging procedure, in which technetium 99m-sulfur colloid is
      injected into the peritoneal cavity prior to imaging of the chest and abdomen,
      can be used to document this finding. Treatment may include therapeutic
      thoracentesis, salt and water restriction, diuretics, tube thoracostomy with
      pleurodesis, surgical repair or placement of a portosystemic shunt.

PMID- 9262533
TI  - Medical options for early pregnancy termination.
AB  - Newly developed protocols using methotrexate and misoprostol are more than 90
      percent effective in terminating pregnancies of less than seven weeks of
      gestation. Major side effects include cramping and bleeding. In a significant
      minority of women, the abortion is completed only after a prolonged wait.
      Nonetheless, abortions completed with methotrexate and misoprostol have been well
      tolerated and acceptable to patients. Mifepristone (formerly called RU 486) will
      soon be available in the United States. When used with misoprostol, mifepristone
      successfully terminates 94 to 99 percent of early pregnancies.

PMID- 9262534
TI  - Community-acquired pneumonia in adults: initial antibiotic therapy.
AB  - Community-acquired pneumonia is a common infection encountered in clinical
      practice and is the leading cause of death due to infectious disease in the
      United States. To choose initial antimicrobial therapy appropriately, physicians
      must keep informed of recent developments in the epidemiology and clinical
      manifestations of atypical pathogens, antibiotic resistance and new antibiotics.
      Differentiating between "typical" and "atypical" pneumonia based on the initial
      clinical presentation is difficult. Primary treatment for community-acquired
      pneumonia in young adults without comorbidities is erythromycin. Older adults or
      those with comorbidities should be treated with erythromycin plus trimethoprim
      sulfamethoxazole, a second- or third-generation cephalosporin, or a new
      macrolide. Empiric therapy for moderately or severely III hospitalized patients
      usually begins with erythromycin plus a second- or third-generation
      cephalosporin. Physicians should use initial antibiotic therapy for coverage of
      both typical and atypical pathogens.

PMID- 9262535
TI  - Salmeterol in the treatment of chronic asthma.
AB  - Salmeterol is a highly selective beta 2-adrenoreceptor agonist with a long
      duration of action--as long as 12 hours or more. When inhaled twice daily in the
      management of chronic asthma, salmeterol can improve lung function and the
      quality of life for patients with asthma, and reduce acute asthma exacerbations.
      It is also a useful adjunct in the treatment of exercise-induced asthma and
      nocturnal asthma. In patients who continue to have symptomatic asthma despite the
      regular use of an inhaled corticosteroid, salmeterol acts as a secondary
      controller of symptoms and reduces the need for inhaled short-acting beta 2
      agonist "rescues". Since salmeterol is different from other beta 2 agonists,
      patients must be carefully educated in its proper use. Salmeterol should be
      administered in combination with an inhaled anti-inflammatory medication as
      adjunctive therapy, but it should not be used for rescue bronchodilatation.

PMID- 9262536
TI  - NHLBI issues updated guidelines for the diagnosis and management of asthma.

PMID- 9262537
TI  - NIH develops consensus statement on interventions to prevent HIV risk behaviors.

PMID- 9262538
TI  - Foscarnet-Ganciclovir Cytomegalovirus Retinitis Trial: 5. Clinical features of
      cytomegalovirus retinitis at diagnosis. Studies of ocular complications of AIDS
      Research Group in collaboration with the AIDS Clinical Trials Group.
AB  - PURPOSE: To examine associations of systemic and ocular characteristics with
      severity of cytomegalovirus (CMV) retinitis at time of diagnosis and to compare
      ocular characteristics of eyes with and without CMV retinitis. METHODS: Eleven
      clinical centers, a data coordinating center, and a fundus photograph reading
      center participated in a randomized, controlled, multicenter clinical trial
      comparing foscarnet and ganciclovir as primary therapy for previously untreated
      CMV retinitis in 240 patients with AIDS. RESULTS: The systemic characteristics
      marginally associated with the percentage of retina affected by CMV in a
      patient's worse eye at diagnosis were chronic fever, weight loss, and number of
      HIV-related illnesses. A positive CMV blood culture at diagnosis was similarly
      associated with bilateral disease. Laboratory measures of disease did not
      correlate well with measures of CMV retinitis severity. Many eyes with CMV
      retinitis had no or minimal lesion hemorrhage, but most had signs of
      inflammation. Patients often reported visual symptoms for involved eyes. The
      worse eyes (the eye with lesions covering the most retinal area) of patients with
      bilateral disease had greater retinal involvement, more lesions, and fewer
      degrees of visual field than did involved eyes of patients with unilateral
      disease. Visual symptoms, inflammation, indolent retinitis, and hemorrhagic
      lesions were associated with a greater percentage of retina affected by CMV.
      CONCLUSIONS: The findings support viremia as a mechanism of spread for untreated
      disease. Visual symptoms and signs of ocular inflammation were indicators both of
      the presence of CMV retinitis and of greater extent of retinal area covered by
      CMV retinitis lesions.

PMID- 9262539
TI  - Analysis of visual dysfunctions in HIV-positive patients without retinitis.
AB  - PURPOSE: To investigate visual dysfunctions in ophthalmoscopically normal human
      immunodeficiency virus (HIV)-positive patients and to correlate the results to
      the stage of HIV disease and neuropsychological status. METHODS: Fifty-one
      randomly selected eyes (26 right, 25 left) of 51 HIV-positive patients with
      visual acuity measurements of 20/20 or better and no ophthalmoscopically
      detectable disorders were prospectively examined using achromatic and short
      wavelength automated perimetry, color vision testing, and contrast sensitivity
      testing. CD4+ T-lymphocyte count, presence of systemic infection, hemoglobin,
      hematocrit, serum beta 2-microglobulin levels, and results of neuropsychological
      testing were also analyzed. RESULTS: On achromatic automated perimetry, 21.6%
      (11/51) of patients performed abnormally according to the mean defect and 27.5%
      (14/51) according to the Glaucoma Hemifield Test; 29.4% (15/51) performed
      abnormally on short-wave-length automated perimetry according to the mean defect
      and 23.5% (12/51) according to the Glaucoma Hemifield Test. On contrast
      sensitivity, 5.9% (3/51) of patients performed abnormally in the 1.5-cycles per
      degree (cpd) line, 2.0% (2/51) in the 3-cpd line, 23.5% (12/51) in the 6-cpd
      line, 25.5% (13/51) in the 12-cpd line, and 33.3% (17/51) in the 18-cpd line. On
      the Farnsworth-Munsell 100-hue test, 29.4% (15/51) of patients performed
      abnormally. After correction for multiple correlations, two statistically
      significant correlations were found: sum of log contrast sensitivity with
      achromatic automated perimetry and sum of log contrast sensitivity with the
      Farnsworth-Munsell 100-hue test. CONCLUSIONS: A significant percentage of HIV
      positive patients with visual acuity of 20/20 or better and no ophthalmologic
      evidence of retinitis performed abnormally on visual psychophysical tests. The
      severity of visual dysfunction was not correlated with the stage of HIV infection
      or the degree of neuropsychological dysfunction.

PMID- 9262540
TI  - Intraocular pressure and aqueous humor dynamics in patients with AIDS treated
      with intravitreal cidofovir (HPMPC) for cytomegalovirus retinitis.
AB  - PURPOSE: To evaluate the decrease in intraocular pressure associated with
      cidofovir (1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine dihydrate; HPMPC)
      intravitreal injections. METHODS: We followed up 97 eyes of 63 patients with
      acquired immunodeficiency syndrome (AIDS) who had cytomegalovirus retinitis and
      had been treated with up to nine 20-microgram intravitreal cidofovir injections.
      Measurements were taken at baseline, between 2 and 3 weeks, and at 5 to 6 weeks
      after injections. Anterior chamber fluorophotometry was studied in seven eyes
      (four patients) before and after injections. Ciliary body anatomy was evaluated
      in two patients. RESULTS: After the first intravitreal injection, mean
      intraocular pressure was 2.2 mm Hg lower than that at baseline at 2 to 3 weeks (P
      < .001) and 1.3 mm Hg lower than at baseline at 5 to 6 weeks (P = .0025). After
      the second injection, mean pressure was 2.6 mm Hg lower at 2 to 3 weeks (P =
      .0013) and 1.5 mm Hg lower at 5 to 6 weeks (P = .043). After subsequent
      injections, however, the decrease was less than 1 mm Hg, suggesting that a
      plateau had been reached. Pressure in eyes with anterior uveitis after the first
      injection was lower than that in eyes without anterior uveitis (P < .0001). The
      mean rate of aqueous flow decreased from 2.8 to 1.9 microliters per minute 2 to 4
      weeks after injection (P < .015). Ultrasound biomicroscopy disclosed that severe
      hypotony after cidofovir injections is associated with ciliary body atrophy.
      CONCLUSIONS: Intraocular pressure decreases after the initial 20-microgram
      cidofovir intravitreal injection. However, eyes stabilize (pressure plateaus)
      after three injections. Effects on the ciliary body are the main cause of the
      decrease after cidofovir injections.

PMID- 9262541
TI  - An in vivo model of human cytomegalovirus retinal infection.
AB  - PURPOSE: To develop an animal model system in which human retina implanted in the
      anterior chamber of the eyes of rats would support human cytomegalovirus
      replication. Cytomegalovirus retinitis currently represents the most common cause
      of posterior uveitis in many urban areas in North America. Despite the tremendous
      interest in cytomegalovirus retinitis as a result of the acquired
      immunodeficiency syndrome (AIDS) epidemic, human cytomegalovirus infection has
      been difficult to model in vivo because of its extreme species-specificity.
      METHODS: Human retina was introduced into the anterior chamber of athymic rats
      and allowed to attach to the rat iris. A human cytomegalovirus mutant carrying a
      beta-galactosidase indicator gene was then injected into the anterior chamber to
      infect the implanted tissue. After 4 weeks, the eyes were removed, sectioned, and
      developed with a chromogenic substrate to demonstrate the presence and location
      of beta-galactosidase expression. RESULTS: Multiple spreading foci of beta
      galactosidase expression were found in the retinal implants, indicating that
      human cytomegalovirus replication had occurred within the human tissue. There was
      no infection of rat tissue. CONCLUSIONS: This model allows human cytomegalovirus
      infection of human retina to be established in vivo and sustained long enough to
      permit multiple cycles of viral replication to occur. The model thus has
      potential for evaluating antiviral therapies directed against human
      cytomegalovirus retinal disease.

PMID- 9262542
TI  - Elevation of laser flare photometry in patients with cytomegalovirus retinitis
      and AIDS.
AB  - PURPOSE: To investigate an alteration of the blood-ocular barriers by laser flare
      photometry in patients with acquired immunodeficiency syndrome (AIDS) diagnosed
      with cytomegalovirus retinitis. METHODS: Serial laser flare photometry
      measurements from 31 eyes of 31 patients with AIDS and newly diagnosed
      cytomegalovirus retinitis were compared with measurements from 31 control
      patients with AIDS but without documented eye disease. Location and extent of
      retinitis, presence of visual symptoms, and CD4 lymphocyte counts were also
      compared with laser flare photometry readings. RESULTS: Laser flare readings
      (mean +/- SE) were significantly higher in eyes with (13.0 +/- 1.5 photon counts
      per msec) than without cytomegalovirus retinitis (4.9 +/- 0.3 photon counts per
      msec) (P < .001). Lesions within the arcade vessels resulted in significantly
      higher laser flare photometry readings (17.3 +/- 2.5 photon counts per msec)
      compared with peripheral retinitis (9.8 +/- 1.5 photon counts per msec) (P =
      .01). A significant correlation was found between area of involvement of
      peripheral retinitis and laser flare photometry readings (P = .008). Readings in
      patients without cytomegalovirus retinitis increased significantly 10 months
      after the first measurement (9.5 +/- 1.9 photon counts per msec) (P = .04).
      Readings in patients with cytomegalovirus remained elevated 3 months after
      successful treatment of retinitis (12.3 +/- 2.3 photon counts per msec) (P = .6).
      CONCLUSIONS: Laser flare photometry readings are significantly elevated in eyes
      with cytomegalovirus retinitis, suggesting a breakdown of the blood-ocular
      barriers. Increasing laser flare photometry readings over time in patients
      without known ocular disease suggests that HIV infection may cause progressive
      breakdown of the blood-ocular barrier.

PMID- 9262543
TI  - Regression of cytomegalovirus retinitis associated with protease-inhibitor
      treatment in patients with AIDS.
AB  - PURPOSE: To report the observation that anti-retroviral therapy that includes a
      protease inhibitor can induce the regression of cytomegalovirus retinitis without
      requiring specific anticytomegalovirus drug therapy. METHODS: We examined the
      fundi of four patients with advanced acquired immunodeficiency syndrome (AIDS)
      who were placed on highly active antiretroviral therapy consisting of two
      nucleoside analogs and a protease inhibitor. The combined medications resulted in
      increased CD4+ T-lymphocyte counts and decreased load of human immunodeficiency
      virus (HIV-1). A prospective evaluation of the effect of these medications on an
      active cytomegalovirus retinitis lesion was conducted in one patient. Retinal
      lesions were documented with fundus photography. RESULTS: None of these patients
      received specific anticytomegalovirus medications. The average baseline CD4+ T
      lymphocyte count was 33 cells per microliter (range, 4 to 88 cells per
      microliter) and increased an average of 118.5 cells per microliter (range, 66 to
      185 cells per microliter). Average baseline plasma HIV-1 viral loads (HIV-1-RNA
      copies per ml) decreased 1.46 log units (range, 0.65 to 2.93 log units). In one
      patient, posterior progression (border advancement toward the posterior pole) of
      a cytomegalovirus retinitis lesion decelerated over time and stopped. Three other
      patients on initial examination had areas of retinal scarring consistent with
      healed cytomegalovirus retinitis. CONCLUSIONS: The addition of an HIV-1 protease
      inhibitor in the treatment of AIDS may lead to complete regression of
      cytomegalovirus retinitis without specific anticytomegalovirus medications. This
      effect may be related to reduced HIV-1 loads, a possible direct drug effect, an
      increase in CD4+ T-lymphocyte counts, or other associated changes in immune
      status.

PMID- 9262544
TI  - Lack of virus transmission by the excimer laser plume.
AB  - PURPOSE: To test the possibility of pathogenic virus transmission into the
      operating suite during excimer laser treatment of corneal tissue. Such treatment
      vaporizes corneal tissue, which may put the surgeon at risk of infection from
      human immunodeficiency virus, hepatitis virus, or other viruses. We developed a
      model system to test the possibility of such virus transmission. METHODS:
      Pseudorabies virus is a porcine enveloped herpesvirus similar in structure and
      life cycle to human immunodeficiency virus and herpes simplex virus. An excimer
      laser was used to ablate a virus-infected tissue culture plate while an
      uninfected tissue culture plate was in an inverted position over the infected
      plate. Six hundred laser pulses were applied. Pseudorabies virus in the excimer
      laser plume would, potentially, contact and infect the uninfected cells. The
      experiment was repeated 20 times with appropriate positive and negative controls.
      RESULTS: None of the 20 uninfected plates was infected by the laser plume rising
      from ablation of infected tissue culture plates. Positive and negative controls
      performed as expected. CONCLUSIONS: Even under conditions designed to maximize
      the likelihood of virus transmission, the excimer laser ablation plume does not
      appear capable of transmitting this particular live enveloped virus. Excimer
      laser ablation of the cornea of a human immunodeficiency virus (HIV)-infected or
      herpesvirus-infected patient is unlikely to pose a health hazard to the surgeon.

PMID- 9262545
TI  - Superficial keratopathy in intensive care unit patients.
AB  - PURPOSE: To determine the prevalence of keratopathy in a randomly selected group
      of hospitalized patients in the intensive care unit and to identify factors
      associated with an increased incidence of corneal abnormalities. METHODS: We
      conducted bedside examinations with a portable slit lamp on 50 randomly selected
      patients. Evidence of superficial keratopathy was recorded. Associated factors
      analyzed included Glasgow Coma Scale, period in the intensive care unit,
      intubation status, underlying disease, and current eye care. RESULTS: Superficial
      keratopathy was present in 20 (40%) of the patients. Of these 20, 18 (90%) were
      intubated, whereas of the remaining 30 patients without corneal abnormalities,
      only 15 (50%) were intubated (P < .01). Fourteen (70%) of the 20 patients with
      corneal abnormalities had been hospitalized in the intensive care unit for 1 week
      or longer compared with 10 (33%) of the 30 patients without corneal abnormalities
      (P = .03). Twelve (60%) of the 20 patients with corneal abnormalities had Glasgow
      Coma Scale scores of 7 or less compared with seven (23%) of the 30 patients
      without corneal abnormalities (P < .03). Only one of the 20 patients with
      superficial keratopathy was receiving ocular lubrication. CONCLUSIONS: The
      prevalence of corneal abnormalities in the critically ill patient reflects
      certain predictors of keratopathy, including the Glasgow Coma Scale, length of
      hospitalization, intubation, and significant metabolic derangement. More
      ophthalmologic attention must be given to patients in intensive care units to
      prevent the development of ocular disease.

PMID- 9262546
TI  - Macular pattern retinal dystrophy, adult-onset diabetes, and deafness: a family
      study of A3243G mitochondrial heteroplasmy.
AB  - PURPOSE: To correlate mitochondrial DNA (mtDNA) mutation with phenotypic
      expression in three members of a Finnish family with macroreticular pattern
      dystrophy, non-insulin-dependent diabetes mellitus, and deafness. METHODS: A
      multiplex polymerase chain reaction/allele-specific oligonucleotide method was
      used to screen 10 mtDNA point mutations known to cause mitochondrial DNA
      disorders, often characterized by myopathy, retinopathy, or both. Quantitative
      analysis of mutant mitochondrial DNA was performed in three tissue types in each
      of three family members by determining the percentage of mutant mtDNA in blood,
      buccal cells, and hair follicles. RESULTS: A heteroplasmic A3243G mtDNA point
      mutation was found in each of the three family members studied. Heteroplasmy
      refers to the coexistence of normal and mutant mitochondria in the same cell. The
      average percentage of mutant heteroplasmy ranged from 11% to 25%. The severity of
      disease symptoms did not appear to correlate with the average degree of mutant
      heteroplasmy in the three tissues analyzed. CONCLUSIONS: Molecular confirmation
      in this family emphasizes the importance of mitochondrial DNA mutation analysis
      in patients with macular pattern retinal dystrophy and other mitochondrial
      associated nonocular disease, such as non-insulin-dependent diabetes mellitus and
      deafness. The detection of a disease-associated mitochondrial DNA mutation
      warrants genetic counseling, appropriate patient follow-up, and possibly the
      molecular testing of other at-risk family members.

PMID- 9262547
TI  - Giant retinal tear as a complication of attempted removal of intravitreal lens
      fragments during cataract surgery.
AB  - PURPOSE: To report giant retinal tear and retinal detachment as a complication of
      attempted removal of intravitreal lens fragments at the time of cataract surgery
      and to evaluate the anatomic and visual acuity outcomes of pars plana vitrectomy
      and retinal reattachment surgery. METHODS: Retrospectively, 10 patients with
      giant retinal tear, retinal detachment, and intravitreal lens fragments in 10
      eyes were reviewed. RESULTS: In 10 eyes, retrieval of intravitreal lens fragments
      using the limbal approach by deep vitrectomy, copious vitreous cavity irrigation,
      or deep vitreous cavity phacoemulsification had been attempted by the anterior
      segment surgeon at the time of cataract surgery in each patient. The average
      interval from cataract surgery to the initial vitreoretinal consultation was 8
      days. Each of the 10 eyes had a giant retinal tear involving the inferior retina:
      in four eyes, of between 90 degrees and 180 degrees; in four, equal to 180
      degrees; and in two, of greater than 180 degrees. After pars plana vitrectomy and
      retinal detachment repair, nine (90%) of 10 eyes had retinal reattachment, but
      seven patients required more than one operation. One eye had persistent retinal
      detachment, and one eye had corneal graft failure. Seven (70%) of the 10 eyes had
      best-corrected final visual acuity of 20/200 or better; three eyes had light
      perception, hand-motion, and counting-fingers vision. CONCLUSIONS: Aggressive
      attempts at intravitreal lens fragment retrieval from a limbal-based approach
      should be avoided because these procedures may result in serious retinal
      complications, such as formation of a giant retinal tear.

PMID- 9262548
TI  - AIDS and ophthalmology: a period of transition.

PMID- 9262549
TI  - Antiviral chemoprophylaxis after occupational exposure to human immunodeficiency
      virus: why, when, where, and what.
AB  - PURPOSE: To update ophthalmologists on recent developments in the area of
      antiviral chemoprophylaxis after occupational exposure to human immunodeficiency
      virus (HIV). Background information is provided by which to make an informed
      decision about whether to initiate antiviral chemoprophylaxis against HIV
      infection. METHODS: We discuss why HIV postexposure prophylaxis should be
      considered; when prophylaxis should be initiated; where prophylaxis medications
      should be located in the operating or emergency room; and what medications might
      be used and the factors influencing their selection. Recent provisional
      recommendations by the United States Centers for Disease Control and Prevention
      and the International AIDS Society-USA are reviewed along with literature dealing
      with antiviral chemoprophylaxis against HIV infection. RESULTS: Recommendations
      are made for specific antiviral chemoprophylaxis after occupational exposure to
      HIV based on the Centers for Disease Control and Prevention and the International
      AIDS Society-USA provisional recommendations. Uncertain areas and the minor
      discrepancies in these two reports are discussed. CONCLUSIONS: Prevention of HIV
      transmission after accidental occupational exposure is possible. Combination
      therapy is more effective than monotherapy in treating HIV infections. Zidovudine
      (AZT or ZDV) is effective in postexposure prophylaxis; the combination of
      zidovudine and lamivudine (3TC) and indinavir (IDV) has greater antiretroviral
      activity than zidovudine alone does. The requirements for effective HIV
      postexposure prophylaxis may be somewhat different than those for optimum HIV
      treatment in the chronically ill HIV-positive patient. Ophthalmologists should
      have an in-depth knowledge of current thinking regarding HIV pathophysiology and
      treatment.

PMID- 9262550
TI  - Molluscum contagiosum eyelid lesions as the initial manifestation of acquired
      immunodeficiency syndrome.
AB  - PURPOSE: To report molluscum contagiosum as the initial manifestation in acquired
      immunodeficiency syndrome (AIDS). METHOD: Case report. A 34-year-old man was
      examined with atypical, extensive molluscum contagiosum of the eyelids. RESULTS:
      Biopsy of the lesions confirmed molluscum contagiosum, and a previously normal
      fundus now disclosed bilateral cotton wool spots and classic signs of
      cytomegalovirus retinitis in the left eye. Human immunodeficiency virus (HIV)
      antibody testing was positive. CONCLUSIONS: Manifestation of atypical and
      extensive eyelid molluscum contagiosum may warrant additional history taking,
      comprehensive ophthalmic examination, including dilated ophthalmoscopic
      examination, and HIV testing.

PMID- 9262551
TI  - Ocular and sinus microsporidial infection cured with systemic albendazole.
AB  - PURPOSE: To report treatment of a patient with acquired immunodeficiency syndrome
      (AIDS) and ocular and paranasal sinus microsporidial infection. METHOD: Case
      report. RESULTS: A patient with AIDS and ocular microsporidial infection
      experienced resolution of ocular symptoms with topical fumagillin, but symptoms
      recurred upon cessation of therapy. Paranasal sinus microsporidial infection was
      diagnosed. The patient received sequential systemic treatment with itraconazole
      followed by albendazole. Sinus symptoms resolved with albendazole. He remained
      symptom-free with a normal examination 17 months after concluding therapy.
      CONCLUSIONS: Although fumagillin and itraconazole may have played a role,
      systemic albendazole appears to be responsible for clinical resolution of
      microsporidial infection.

PMID- 9262552
TI  - Metastatic anterior chamber non-Hodgkin lymphoma in a patient with acquired
      immunodeficiency syndrome.
AB  - PURPOSE: To alert ophthalmologists to the possibility of metastatic anterior
      chamber intraocular non-Hodgkin lymphoma in patients with acquired
      immunodeficiency syndrome (AIDS). METHODS: We examined a 19-year-old man with
      AIDS who had an anterior uveitis with pseudohypopyon and a history of 2 months of
      malaise. A specimen of the lesion was obtained with a 25-gauge needle for
      pathologic examination. RESULTS: Systemic exploration showed hepatomegaly.
      Abdominal computed tomography showed multiple lesions in the liver and spleen.
      Fine-needle aspiration disclosed a high-grade non-Hodgkin lymphoma. The result of
      a fine-needle aspiration obtained from a lesion in the anterior chamber was
      consistent with the same diagnosis. CONCLUSION: An anterior chamber
      pseudohypopyon with uveitis can be the manifesting sign of a systemic lymphoma in
      a patient with AIDS and requires a thorough systemic evaluation.

PMID- 9262553
TI  - Damage of foldable intraocular lenses by incorrect folder forceps.
AB  - PURPOSE: To evaluate possible damage of foldable silicone or acrylic intraocular
      lenses caused by the use of incorrect lens folder forceps. METHODS: Ten silicone
      and 10 acrylic intraocular lenses were divided into two groups, each containing
      five silicone and five acrylic lenses. Two easily mistaken folder forceps, each
      expressly designed for either silicone or acrylic lenses only were properly used
      to fold the intraocular lenses in group 1 whereas in group 2, the silicone lenses
      were folded with the forceps designed for the acrylic lenses, and the acrylic
      lenses were folded with the forceps designed for the silicone lenses. We observed
      the lenses by transmission and scanning microscopy after folding. RESULT: The
      acrylic lenses folded with forceps designed for the silicone lenses (group 2)
      disclosed considerable damage of the lens optic. CONCLUSION: Incorrect folder
      forceps may damage acrylic intraocular lenses.

PMID- 9262554
TI  - Atrophic fundus lesions associated with untreated retinopathy of prematurity.
AB  - PURPOSE: To document that lacunar, atrophic lesions of the retinal pigment
      epithelium, previously reported as a complication of treatment, can result from
      the natural course of retinopathy of prematurity. METHODS: We reviewed
      photographs of patients diagnosed with retinopathy of prematurity at the Casey
      Eye Institute between 1979 and 1996. Lacunar atrophic lesions of the retinal
      pigment epithelium were correlated with the clinical records of the affected
      patients. RESULT: Three untreated eyes of three patients with retinopathy of
      prematurity had lacunar atrophic lesions of the retinal pigment epithelium.
      CONCLUSIONS: The spectrum of findings associated with untreated retinopathy of
      prematurity includes lacunar, atrophic lesions of the retinal pigment epithelium.
      These lesions are distinct from scars secondary to treatment and are possibly
      linked to macular dragging and exudative or serous retinal detachment.

PMID- 9262555
TI  - Peripapillary staphyloma.
AB  - PURPOSE: To report a rare case of peripapillary staphyloma. METHOD: Case report.
      A 5-month-old infant was examined for esotropia associated with a retinal and
      optic nerve abnormality of the left eye. RESULTS: Detailed clinical examination
      along with diagnostic ultrasonography and electroretinography established a
      diagnosis of a peripapillary staphyloma of the left eye measuring 9.77 mm in
      depth. The patient's right eye was entirely normal, and she showed no systemic
      abnormalities. CONCLUSION: Although extremely rare, the peripapillary staphyloma
      may cause severe visual impairment of the affected eye in an otherwise healthy
      individual unassociated with systemic abnormalities.

PMID- 9262556
TI  - Angle-closure glaucoma in a 10-year-old girl.
AB  - PURPOSE: To report a case of angle-closure glaucoma in a 10-year-old girl with
      ocular albinism. METHODS: Case report. A 10-year-old girl with autosomal
      recessive ocular albinism was examined and treated for subacute angle-closure
      glaucoma of the right eye. RESULT: The patient was successfully treated with
      Nd:YAG laser iridotomy of the right eye. CONCLUSIONS: Angle-closure glaucoma may
      rarely occur in young or adolescent children. Gonioscopy of children with shallow
      anterior chambers is recommended.

PMID- 9262557
TI  - Idiopathic intracranial hypertension in children and adolescents.
AB  - PURPOSE: To investigate sex distribution, frequency of obesity, and other
      associated conditions among children and adolescents with idiopathic intracranial
      hypertension. METHODS: We conducted a retrospective chart review of patients aged
      18 years or younger diagnosed with idiopathic intracranial hypertension between
      1988 and 1995 at two medical centers. Meta-analyses were performed using our data
      pooled with published information. RESULTS: Of 374 patients, 175 (46.8%) were
      male and 199 (53.2%) were female. Obesity was noted in 50 (29.6%) of the 169
      patients for whom relevant data are available, and other associated conditions
      were noted in 185 (53.2%) of the 348 patients. CONCLUSIONS: Idiopathic
      intracranial hypertension among children and adolescents affects boys and girls
      equally; concurrent obesity occurs less frequently than in adults; and other
      associated conditions or secondary causes are common.

PMID- 9262559
TI  - Retinal vein occlusion and transient monocular visual loss associated with
      hyperhomocystinemia.
AB  - PURPOSE: To report a 24-year-old man with bilateral central retinal vein
      occlusions who had preceding episodes of prolonged transient monocular visual
      loss during which ophthalmoscopic findings were not suggestive of vein occlusion.
      METHOD: Case report. RESULT: Extensive hematologic studies for causes of vein
      occlusion were unremarkable with the exception of increased plasma homocysteine
      in the patient and in his asymptomatic father. CONCLUSIONS: Impending vein
      occlusion should be considered in the differential diagnosis of transient
      monocular visual loss regardless of ophthalmoscopic appearance, and
      hyperhomocystinemia should be considered as a possible cause of retinal vein
      occlusion.

PMID- 9262558
TI  - Recurrent abducens nerve palsy caused by dolichoectasia of the cavernous internal
      carotid artery.
AB  - PURPOSE: To describe a 59-year-old patient who had seven recurrent, self-limited
      episodes of isolated ipsilateral abducens nerve palsy in the previous 4 years.
      Each episode lasted between 2 and 5 weeks. METHODS: Systemic examination and
      neuroimaging studies were performed. RESULT: Repeated comprehensive examination
      failed to demonstrate any ocular or systemic condition apart from a lateral
      protrusion by dolichoectasia of the posterior portion of the cavernous left
      internal carotid artery, compressing the posterior left cavernous sinus.
      CONCLUSION: Numerous self-limited episodes of sixth nerve palsy may be associated
      with structural abnormalities of the intracranial carotid vasculature.

PMID- 9262560
TI  - Echographic diagnosis of scleral fold in hypotony.
AB  - PURPOSE: To report the echographic appearance of a scleral fold in hypotony.
      METHOD: We performed ultrasonography on a patient who, after trabeculectomy with
      mitomycin C, had an intraocular pressure of 1 mm Hg, an opaque cataract, and
      suspected hypotonous maculopathy in the left eye. RESULTS: An area of dome-shaped
      eyewall thickening was noted near the tendon of the lateral rectus muscle in
      primary gaze. This thickening increased substantially in lateral gaze, mimicking
      a foreign body or a tumor. CONCLUSION: Recognizing this abnormality is important
      to avoid erroneous diagnosis of an intraocular foreign body or a tumor in
      hypotonous eyes.

PMID- 9262562
TI  - Sectorial choroidal ischemia associated with ipsilateral lacrimal gland tumor.
AB  - PURPOSE: To report the association of sectorial choroidal ischemia with
      ipsilateral tumor of the lacrimal gland. METHODS: Case report. In a 62-year-old
      man, a complete ophthalmologic examination, including fluorescein angiography and
      computed tomographic scans of the orbit, was performed. The patient underwent an
      en bloc excisional biopsy of the tumor. RESULTS: Fluorescein angiography of the
      left eye showed extensive sectorial choroidal ischemia superotemporal to the
      optic disk with macular involvement and associated chorioretinal folds. The
      patient was found to have a benign mixed tumor of the left lacrimal gland.
      CONCLUSION: The tumor of the lacrimal gland may have compressed choroidal vessels
      and short posterior ciliary arteries with subsequent sectorial choroidal
      ischemia.

PMID- 9262561
TI  - Ophthalmic findings in a case of hemophagocytic syndrome.
AB  - PURPOSE: To report a case of hemophagocytic syndrome, which is characterized by
      hemophagocytosis of histiocytes; optic nerve involvement, and unusual retinal
      white patches. METHOD: Case report. A 10-year-old boy had repeated relapses of
      hemophagocytic syndrome. He complained of swelling of the right upper eyelid and
      bilateral visual disturbance. RESULTS: Ophthalmoscopic examination disclosed
      bilateral optic disk edema, retinal hemorrhages, and multiple perivenous white
      patches in the retina. Magnetic resonance imaging demonstrated enlargement of
      both optic nerves. After chemotherapy and bone marrow transplantation, his visual
      acuity improved in both eyes, and retinal patches changed to inactive-appearing
      scars. CONCLUSION: Hemophagocytic syndrome may manifest with ophthalmic findings
      such as optic nerve involvement, retinal hemorrhages, and multiple white
      perivenous retinal patches.

PMID- 9262563
TI  - Frozen section--guided surgical debridement for management of rhino-orbital
      mucormycosis.
AB  - PURPOSE: To present a new method of surgical treatment for rhino-orbital
      mucormycosis. METHOD: We treated a patient with extensive surgical debridement of
      mucormycosis with intraoperative frozen section guidance. The patient did not
      require exenteration. RESULT: Our patient survived with normal vision and no
      diplopia. CONCLUSIONS: Frozen section-guided surgical debridement in rhino
      orbital mucormycosis may provide an alternative to traditional radical surgical
      excision. In selected cases, this new method of treatment may cause less
      morbidity than do traditional treatments.

PMID- 9262564
TI  - Pulmonary lobectomy patient care pathway: a model to control cost and maintain
      quality.
AB  - BACKGROUND: Cost containment is a reality in thoracic surgery. Patient care
      pathways have proved effective in cardiac surgery to reduce length of stay and
      control costs. METHODS: A multidisciplinary team formulated a pulmonary lobectomy
      patient care pathway to standardize care, reduce length of stay and costs, and
      maintain quality. Variance codes were developed to collect data prospectively on
      reasons for prolonged stay. A patient satisfaction survey was instituted to learn
      patients' responses to their hospitalization. RESULTS: One hundred forty-seven
      patients underwent lobectomy in 1995 before institution of the pathway with a
      mean length of stay of 10.6 days and a mean cost of $16,063. The lobectomy
      pathway was instituted at the beginning of 1996. One hundred thirty patients
      underwent lobectomy in 1996 with a mean length of stay of 7.5 days (p = 0.03) and
      a mean cost of $14,792 (p = 0.47). Readmission and mortality rates were
      unchanged. Eighty-eight of 130 patients (68%) were able to be discharged by the
      target length of stay of 7 days in 1996 as opposed to 76 of 147 patients (52%) in
      1995. The most common reason for delayed discharge was inadequate pain control.
      The majority of patients felt prepared for discharge by the seventh postoperative
      day (70 of 96 patients, 73%). CONCLUSIONS: The institution of a lobectomy patient
      care pathway appeared to reduce length of stay and costs. The pathway provided a
      framework to begin systematic quality control measures to enhance patient care.

PMID- 9262565
TI  - Incidence of lung nodules found in patients undergoing lung volume reduction.
AB  - BACKGROUND: The risk of lung cancer is increased with cigarette smoking and
      obstructive lung disease. Patients having a lung volume reduction operation
      represent a high-risk population for cancer. METHODS: Between March 1994 and
      December 1996, 281 patients underwent a lung volume reduction operation. All had
      severe obstructive lung disease with hyperinflation. The incidence of lung
      nodules and their management were addressed. RESULTS: Of the 281 patients, 39.5%
      had at least one lung nodule identified. Fifty-two nodules had typical benign
      calcification patterns. Of the remaining nodules, 78 were resected and 20 were
      followed up. Seventeen nodules resected were cancerous, of which 13 were primary
      lung cancers. Of the resected nodules there were 28 nodules not identified by the
      preoperative radiologic evaluation. CONCLUSIONS: Nodules are frequently seen in
      patients undergoing lung volume reduction operations. The overall incidence of
      cancer was 6.4%, with several only identified in the pathologic examination.
      Survival at short follow-up has been excellent for those with primary lung
      cancer. Nodules seen in this group of patients should be aggressively diagnosed
      and managed.

PMID- 9262567
TI  - Radiologic emphysema morphology is associated with outcome after surgical lung
      volume reduction.
AB  - BACKGROUND: Lung volume reduction surgery is known to alleviate dyspnea and to
      improve pulmonary function, performance in daily activity, and quality of life in
      selected patients with severe pulmonary emphysema. We investigated the role of
      radiologically assessed emphysema morphology on functional outcome after a lung
      volume reduction operation. METHODS: The preoperative chest computed tomograms in
      50 consecutive patients who had undergone surgical lung volume reduction were
      retrospectively reviewed by 6 physicians blinded to the clinical outcome.
      Emphysema morphology was determined according to a simplified classification (ie,
      homogeneous, moderately heterogeneous, and markedly heterogeneous; lobe
      predominance). We studied the impact of these morphologic aspects on functional
      outcome at 3 months. RESULTS: We found a fair interobserver agreement applying
      our classification system. Functional improvement after surgical lung volume
      reduction was best in markedly heterogeneous emphysema with an increase in forced
      expiratory volume in 1 second of 81% +/- 17% (mean +/- standard error, n = 17)
      compared with 44% +/- 10% (n = 16) for intermediately heterogeneous emphysema.
      But also in patients with homogeneous emphysema clinical relevant improvement of
      function could be observed (increase in forced expiratory volume in 1 second =
      34% +/- 6%; n = 17). CONCLUSIONS: The morphologic type of emphysema, assessed by
      a simplified surgically oriented classification, is an important predictor of
      surgical outcome. Lung volume reduction surgery may also improve dyspnea and lung
      function in homogeneous emphysema.

PMID- 9262566
TI  - Use of over-sized mature pulmonary lower lobe grafts results in superior
      pulmonary function.
AB  - BACKGROUND: Mature lobar transplantation will increase the pediatric donor organ
      pool; however, issues regarding size discrepancy between donor grafts and
      recipient lungs remain unresolved. We hypothesized that an oversized mature
      pulmonary lobar allograft implanted into an immature recipient would provide
      adequate longterm pulmonary function versus a size-matched mature lobar graft or
      an immature whole lung. METHODS: We investigated our hypothesis in a porcine
      orthotopic left lung transplant model in which 19 immature animals made up one
      control and three recipient groups. Group I underwent sham left thoracotomy
      (control, n = 4). Group II received age- and size-matched immature whole left
      lung transplant (n = 6). Group III received mature size-matched left upper lobe
      transplants (n = 4). Group IV received mature over-sized left lower lobe
      transplants (n = 5). Twelve weeks after implantation, data were collected after
      the native right lung was excluded. RESULTS: Graft weight was significantly
      elevated in group IV as compared with the explanted lung (72.4 +/- 6.8 versus
      38.3 +/- 4.5 g; p = 0.003). Pulmonary artery pressure and pulmonary vascular
      resistance were significantly elevated in group III as compared with the over
      sized mature lower lobe transplants (51.8 +/- 2.2 versus 40.4 +/- 2.5 mm Hg [p <
      0.0001] and 1,605.9 +/- 117.5 versus 857.6 +/- 133.6 dynes.s.cm-5 [p < 0.0005],
      respectively). A trend toward decreased oxygenation was identified in group II.
      CONCLUSIONS: Over-sized mature lobar grafts provide improved hemodynamics as
      compared with size-matched grafts. Mature left lower lobe grafts are superior to
      size-matched upper lobe grafts in this model, probably as a result of an
      augmented vascular bed.

PMID- 9262568
TI  - Functional comparison of unilateral versus bilateral lung volume reduction
      surgery.
AB  - BACKGROUND: Lung volume reduction surgery (LVRS) has shown early promise as a
      palliative therapy in severe emphysema. A number of patients, however, are not
      candidates for a bilateral operation, or exhibit a predominantly unilateral
      disease distribution. METHODS: Over 20 months, we performed LVRS in 92 patients
      selected on the basis of severe hyperinflation with air trapping, diaphragmatic
      dysfunction, and disease heterogeneity. Twenty-eight patients underwent
      unilateral LVRS on the basis of asymmetric disease distribution, prior thoracic
      operation, or concomitant tumor resection. RESULTS: Unilateral LVRS resulted in
      comparable improvements in exercise capacity and dyspnea as the bilateral
      procedure, with a similar perioperative mortality and actuarial survival to 24
      months. Improvements in spirometric indices of pulmonary function, however, were
      less in patients undergoing unilateral than bilateral LVRS. CONCLUSIONS: In
      properly selected patients, unilateral LVRS provides functional and subjective
      benefits of comparable magnitude to those associated with a bilateral operation.
      Unilateral LVRS is therefore an option in the therapy of end-stage emphysema in
      patients with asymmetric disease distribution, a prior thoracic operation, or
      contraindications to sternotomy, and may have a role as a bridge to
      transplantation in selected cases.

PMID- 9262569
TI  - Standardized exercise oximetry predicts postpneumonectomy outcome.
AB  - BACKGROUND: We have developed a safe, simple, and easily performed standardized
      exercise oximetry outpatient test to assess patients undergoing lung resections.
      We studied its ability to predict outcome after pneumonectomy in 46 consecutive
      patients over a 5-year period. METHODS: Room air oximetry is initially performed
      at rest. The patient then begins to exercise on a stair-stepper apparatus
      (Stamina Stepper), which provides uniform resistance to stepping. Oxygen
      saturation values are noted at 10, 20, and 30 steps, equivalent to climbing three
      flights of stairs. Group 1 consisted of the patients who either had a resting
      saturation less than 90%, or desaturation greater than or equal to 4% during
      exercise. Group 2 consisted of all patients who had a preoperative forced
      expiratory volume in 1 second of 60% or less. Group 3 consisted of all patients
      who had a predicted postoperative forced expiratory volume in 1 second of 40% or
      less. Group 4 consisted of patients who had a predicted postoperative diffusing
      capacity of 40% or less. RESULTS: There were four deaths (8.6%), 12 patients
      (26%) remained in the intensive care unit 4 or more days, and 11 patients (23%)
      suffered major morbidity. Desaturation during exercise (group 1) significantly
      predicted longer intensive care unit stay (p = 0.0002) and incidence of major
      morbidity (p < 0.0001). Groups 2, 3, and 4 were not significantly predictive of
      either longer intensive care unit stay or major morbidity. CONCLUSIONS:
      Standardized exercise oximetry performed in the outpatient facility is highly
      predictive of major morbidity and prolonged intensive care unit stay after
      pneumonectomy.

PMID- 9262570
TI  - Unusually located hydatid cysts: intrathoracic but extrapulmonary.
AB  - BACKGROUND: Hydatid cyst disease is still a problem in Turkey, as well as in many
      other places in the world. Extrapulmonary location of the disease in the thorax
      is very rare, and surgical procedures can be considered that differ from those
      used for pulmonary hydatid cysts. METHODS: We reviewed retrospectively our
      experience in the surgical treatment of 22 patients with intrathoracic,
      extrapulmonary hydatid cysts. In our department, 297 patients with thoracic
      hydatid cysts were managed surgically in the last 14 years, in 22 (7.4%) of whom
      the cysts were localized extrapulmonarily in the thorax. The locations of these
      hydatid cysts were a fissure, the pleural cavity, chest wall, mediastinum,
      myocardium, and diaphragm. RESULTS: Total resection was chosen as the surgical
      procedure in all patients except 4 (18.2%), 1 of whom had cystectomy and
      capitonnage for cardiac hydatid cyst and 3 of whom had cystectomy and local
      curettage for cysts located in the chest wall. Empyema developed postoperatively
      in 1 case (4.5%) with a cyst in the fissure. The follow-up period was 1 year, and
      there were no deaths. CONCLUSIONS: Hydatid cyst may be found in many different
      sites, including extrapulmonarily in the thorax, and bearing this in mind will
      facilitate planning of the operation.

PMID- 9262571
TI  - One-stage surgical procedure for bilateral lung and liver hydatid cysts.
AB  - BACKGROUND: Echinococcus disease is endemic in areas where livestock are raised
      in association with dogs. The majority of patients reporting in the Department of
      Cardiovascular and Thoracic Surgery at Postgraduate Institute of Medical
      Education and Research have unilateral pulmonary hydatid disease. METHODS: From
      March 1988 to May 1996 we came across 58 patients with pulmonary hydatidosis, of
      which 5 patients presented with combined bilateral pulmonary and hepatic hydatid
      cysts. In these patients, to avoid three-stage operation of two thoracotomies and
      a laparotomy, we proceeded with simultaneous combined resection of hydatid cysts
      in one stage through midsternotomy along with laparotomy or transdiaphragmatic
      removal of liver cysts. RESULTS: Results indicate that combined resection of
      pulmonary and hepatic hydatid cysts is feasible with minimum morbidity and no
      recurrence. CONCLUSIONS: We conclude that a one-stage surgical procedure for
      bilateral lung and liver hydatid cysts is superior to the classic three-stage
      approach as it decreases morbidity, hospital stay, and cost.

PMID- 9262573
TI  - Experimental reconstruction of the mediastinal trachea with a wing-shaped
      reversed esophageal flap.
AB  - BACKGROUND: In cases of extensive tracheal resection in which direct end-to-end
      anastomosis is impossible there is a need for reconstruction. Nevertheless, with
      the present lack of reliable artificial trachea, no reconstruction method is
      available to assure safe replacement of the mediastinal trachea. METHODS: After
      tubular resection of the mediastinal trachea in mongrel dogs, the trachea was
      reconstructed using a wing-shaped reversed esophageal flap. A silicone tube was
      used as an internal stent. RESULTS: In group I (16 animals), three tracheal rings
      were resected; in group II (4 animals), six tracheal rings; in group III (6
      animals), eight tracheal rings; and in group IV (5 animals), eight tracheal rings
      and the lining of the greater omentum. Safe reconstruction was accomplished in
      all cases in groups I and II, 2 of 6 cases in group III, and 2 of 5 cases in
      group IV. The omentopexy failed to prevent incomplete closure, yet served to
      minimize inflammation in the mediastinum. CONCLUSIONS: A reversed esophageal
      autograft can be considered as a tracheal replacement.

PMID- 9262572
TI  - Treatment strategy for patients with surgically discovered N2 stage IIIA non
      small cell lung cancer.
AB  - BACKGROUND: The treatment strategy for patients with non-small cell lung cancer
      and clinically negative, but surgically detected mediastinal lymph node
      metastasis (surgically discovered N2 disease) is controversial. METHODS: From
      August 1979 through December 1994, 53 patients with non-small cell lung cancer
      were found to have surgically discovered N2 disease. We retrospectively studied
      the clinical characteristics and the factors that influenced the prognosis in
      these patients. RESULTS: The 3-year and 5-year survival rates and the median
      survival for the 53 patients with surgically discovered N2 disease were 44%, 21%,
      and 26 months. Two thirds of the patients had adenocarcinoma. Only complete
      resection affected long-term survival; adjuvant therapy had no effect on
      survival. In regard to lymph node status, a single metastatic focus in the aortic
      area was associated with long-term survival. CONCLUSIONS: Patients with
      adenocarcinoma may require histologic determination of N2 disease. Complete
      resection, including extensive and complete mediastinal lymph node dissection, is
      warranted in patients with surgically discovered N2 disease. In particular, when
      the aortic lymph node (including stations 5 and 6) alone is involved, the
      patients should undergo as complete a resection as possible.

PMID- 9262574
TI  - Management of malignant tracheoesophageal fistulas with a cuffed funnel tube.
AB  - BACKGROUND: A detachable cuffed flange tube for the assessment of malignant
      tracheoesophageal fistulas by a minimal invasive surgical insertion technique is
      presented. The funnel cuff of this tube seals the space between the esophageal
      wall and the flange of conventional tubes above the fistula at the level of the
      suprastrictural dilatation. METHODS: Twenty-eight patients having a malignant
      esophagorespiratory fistula with associated primary or secondary esophageal
      stricture, except 1, underwent esophageal intubation with this prosthesis between
      1983 and 1996. RESULTS: All insertion attempts, without previous esophageal
      dilation, were successful. The overall mortality was 7.4%. The cuffed funnel has
      provided hermetic water-tight exclusion of the fistula in all instances.
      Intraabdominal septic complications, reflux, or tube displacement have never
      occurred after use of this intubation technique. CONCLUSIONS: For occlusion of
      malignant respiratory tract fistulas this cuffed flange tube proved to be
      superior to conventional esophageal prostheses.

PMID- 9262575
TI  - Mediastinal growing teratoma syndrome.
AB  - BACKGROUND: The growing teratoma syndrome refers to the phenomenon whereby germ
      cell tumors enlarge after chemotherapy despite complete eradication of malignant
      cells and normalization of serum tumor markers. This clinical scenario must be
      differentiated from that in which germ cell tumors maintain their malignant
      characteristics with elevated levels of serum tumor markers. METHODS: Hospital
      record review was conducted of 2 cases. RESULTS: Two male patients are presented,
      1 with a metastatic germ cell tumor of both the retroperitoneum and mediastinum
      (with elevated alpha-fetoprotein level) and 1 with a primary germ cell tumor of
      the mediastinum (with elevated alpha-fetoprotein and beta-human chorionic
      gonadotropin levels). After completion of chemotherapy and normalization of tumor
      markers, both patients presented with pulmonary symptoms attributable to their
      massively enlarging mediastinal teratomas. The clinical and roentgenographic
      features of patients with thoracic manifestations of the growing teratoma
      syndrome, as well as its management, are reviewed. CONCLUSIONS: After
      chemotherapy in patients with primary or metastatic mediastinal germ cell tumors
      whose tumor markers normalize, a growing mass in the mediastinum may represent
      the growing teratoma syndrome.

PMID- 9262576
TI  - Micrometastatic tumor cells in the bone marrow of patients with non-small cell
      lung cancer.
AB  - BACKGROUND: This study was designed to evaluate the incidence and clinical
      implications of detection of micrometastatic cancer cells in bone marrow
      aspirates of patients with operable non-small cell lung cancer. The relationship
      between micrometastatic cells and p53 overexpression in the primary tumor was
      also assessed. METHODS: Thirty-nine patients with stages I through III non-small
      cell lung cancer who underwent curative resection were entered into this study.
      Immunohistochemistry with monoclonal antibody to cytokeratin 18 was used to
      detect tumor cells in bone marrow. Immunostaining of p53 protein in the
      corresponding primary tumors was also done. RESULTS: Cytokeratin 18-positive
      cells were detected in 15 (39%) of the 39 patients. Overexpression of p53 was
      associated with positivity of the tumor cells in the bone marrow at borderline
      significance (14/29 versus 1/10; p = 0.0574). The patients with cytokeratin 18
      positive cells in bone marrow demonstrated a significantly earlier recurrence
      than those without such cells (p = 0.0083, log-rank test). CONCLUSIONS:
      Micrometastatic cancer cells were frequently present in bone marrow of patients
      with operable non-small cell lung cancer and may be a significant predictor of
      early recurrence. Further evaluation of this method may be useful in identifying
      patients with non-small cell lung cancer who are most likely to benefit from
      adjuvant chemotherapy.

PMID- 9262577
TI  - Intraoperative echocardiography is indicated in high-risk coronary artery bypass
      grafting.
AB  - BACKGROUND: Intraoperative echocardiography is a valuable monitoring and
      diagnostic technology used in cardiac surgery. This reports our clinical study of
      the usefulness of intraoperative echocardiography to both surgeons and
      anesthesiologists for high-risk coronary artery bypass grafting. METHODS: From
      March to November 1995, 82 consecutive high-risk patients undergoing coronary
      artery bypass grafting were studied in a four-stage protocol to determine the
      efficacy of intraoperative echocardiography in management planning. Alterations
      in surgical and anesthetic/hemodynamic management initiated by intraoperative
      echocardiography findings were documented in addition to perioperative morbidity
      and mortality. RESULTS: Intraoperative echocardiography initiated at least one
      major surgical management alteration in 27 patients (33%) and at least one major
      anesthetic/hemodynamic change in 42 (51%). Mortality and the rate of myocardial
      infarction in this consecutive high-risk study population using intraoperative
      echocardiography and in a similar group of patients without the use of
      intraoperative echocardiography was 1.2% versus 3.8% (not significant) and 1.2%
      versus 3.5% (not significant), respectively. CONCLUSIONS: We conclude that when
      all of the isolated diagnostic and monitoring applications of perioperative
      echocardiography are routinely and systematically performed together, it is a
      safe and viable tool that significantly affects the decision-making process in
      the intraoperative care of high-risk patients undergoing primary isolated
      coronary artery bypass grafting and may contribute to the optimal care of these
      patients.

PMID- 9262578
TI  - Intracoronary ultrasound-guided CABG in patients with angiographically
      noncritical lesions. Cardiovascular Surgery Associates.
AB  - BACKGROUND: Coronary angiography is used to determine the severity of coronary
      artery disease; however, in a small group of patients, clinically significant
      angina and physiologic tests indicative of myocardial ischemia do not correlate
      with angiographically demonstrable critical coronary artery disease. In these
      patients intracoronary ultrasound may demonstrate the true severity of lesions.
      METHODS: Eight patients with angina and positive stress testing but without
      angiographically critical left main or left anterior descending artery stenoses
      were retrospectively identified. After intracoronary ultrasonic demonstration of
      critical left main or left anterior descending artery lesions, coronary artery
      bypass grafting was performed. Follow-up evaluation of clinical status and repeat
      stress testing were carried out. RESULTS: Intracoronary ultrasound demonstrated
      critical left main (n = 4) or proximal left anterior descending artery (n = 7)
      stenoses in all patients. Severity of angiographic versus intracoronary
      ultrasound-documented stenoses was (mean +/- standard error of the mean) 10% +/-
      10% versus 65% +/- 10% for left main lesions and 30% +/- 5% versus 75% +/- 5% for
      left anterior descending artery lesions. After coronary artery bypass grafting
      all patients had decreased angina and normalization of stress testing.
      CONCLUSIONS: In patients with clinical presentations indicative of significant
      coronary artery disease but with angiographically noncritical lesions,
      intracoronary ultrasound can accurately assess the severity of stenoses. Coronary
      artery bypass grafting guided by intracoronary ultrasonic findings successfully
      treats myocardial ischemia in these patients.

PMID- 9262579
TI  - The autopsy: still important in cardiac surgery.
AB  - BACKGROUND: This study examined the ability of autopsy to confirm or dispute
      presumptive cause of death among cardiac surgery patients. METHODS: Autopsy
      reports were compared with mortality conference notes that were dictated
      prospectively before autopsy results were available. Between January 1985 and
      December 1995, there were 600 hospital deaths among 13,029 adult cardiac surgery
      patients (4.6% mortality). Of these 600 deaths, 147 (24.5%) had postmortem
      examination. RESULTS: Annual autopsy rate remained constant over the course of
      the study. Autopsied patients were younger (60.4 +/- 15 versus 66.7 +/- 13 years
      [mean +/- standard error of the mean]; p < 0.0001), but their race and sex
      distributions were similar to deceased patients not having autopsy. Autopsy
      confirmed clinical presumptive cause of death in 52% (76), disputed clinical
      diagnosis in 9.5% (14), provided definitive diagnosis in the absence of clinical
      diagnosis in 13.6% (20), and failed to provide definitive diagnosis in 25% (37).
      One third of autopsies (39%; 57) provided information that was clinically
      unrecognized and might have altered therapy and outcome if known premortem. As
      determined by autopsy, common causes of death were cardiac (27%; 39), unknown
      (25%; 37), sepsis (14%; 21), stroke (8.8%; 13), cholesterol embolism (4.1%; 6),
      pulmonary embolism (4.1%; 6), and adult respiratory distress syndrome (4.1%; 6).
      CONCLUSIONS: Autopsy reveals or confirms cause of death in nearly three quarters
      of cardiac surgical deaths and provides information that differs significantly
      from premortem clinical impression more than 20% of the time. As such, the
      autopsy remains important to quality assurance in cardiac surgical care.

PMID- 9262580
TI  - Traumatic aortic transections: eight-year experience with the "clamp-sew"
      technique.
AB  - BACKGROUND: Because traumatic aortic transection is associated with high
      mortality rates, great debate exists about the appropriate operative technique
      for treatment of patients who have acute traumatic aortic transection. METHODS:
      To determine the safety and efficacy of the "clamp-sew" method, we
      retrospectively reviewed our 8-year experience treating 75 patients who had
      aortic injuries secondary to blunt trauma. Seventy-one of these patients were
      treated surgically. The clamp-sew method was used in all of these operations.
      RESULTS: Aortic cross-clamp time averaged 24 minutes (range, 14 to 36 minutes),
      with 4/71 having times in excess of 30 minutes. One patient (clamp time, 28
      minutes) became paraplegic. Significant associated injuries were seen in 51/75
      patients (48/71 patients with operation), including intrathoracic (35 patients),
      orthopedic (28 patients), intraabdominal (24 patients), and central nervous
      system (17 patients) damage. No patient died within 24 hours of operation.
      Overall 30-day mortality was 12% (9/75), with 7/9 having two or more
      aforementioned associated injuries. Of these 7, 5 had central nervous system
      injuries. Two of 9 died within 30 days without two or more associated injuries: 1
      Jehovah's Witness of low hemoglobin, and 1 patient of sepsis. CONCLUSIONS:
      Although any of several maneuvers may be appropriate in managing traumatic aortic
      injuries, the simple "clamp-sew" technique is a safe and effective method for the
      treatment of traumatic aortic transections.

PMID- 9262581
TI  - Heart valve operation in acromegaly.
AB  - BACKGROUND: Intractable congestive heart failure is known as a serious
      complication of acromegaly, but valvular heart disease rarely occurs in
      acromegalic patients. We experienced 5 surgical cases of valvular heart disease
      associated with acromegaly. We describe the features of those cases in this
      report. METHODS: The patient characteristics and operative and pathologic
      findings were retrospectively studied. RESULTS: There were 4 men and 1 women. Age
      at operation was 59 +/- 5.5 years. Cardiac lesions consisted of 1 case of aortic
      regurgitation associated with mitral regurgitation, 1 of aortic regurgitation,
      and 3 of mitral regurgitation. Operative procedures consisted of 1 double valve
      replacement (aortic and mitral valve replacement), 1 aortic valve replacement,
      and 3 mitral valve replacements. The causes of aortic valvular regurgitation were
      aortic valvular degeneration and aortic annular dilatation. The causes of mitral
      regurgitation were chordal rupture and mitral valvular degeneration.
      Histopathologic examination of the excised valves showed mucopolysaccharide
      deposits and myxomatous degeneration of the leaflets. The myocardium showed
      fibrosis of interstitial spaces and endocardium, and disarrangement of muscle
      fibers. CONCLUSIONS: We report 5 successful surgical cases of valvular heart
      disease associated with acromegaly. Earlier operation is recommended for such
      cases because of acromegalic cardiomyopathy.

PMID- 9262582
TI  - Predictors of sinus rhythm restoration after Cox maze procedure concomitant with
      other cardiac operations.
AB  - BACKGROUND: There have been sporadic cases of persistent atrial fibrillation and
      sick sinus syndrome after the maze procedure. The purpose of this study was to
      identify the predictors of sinus rhythm restoration after operation. METHODS:
      Between March 1993 and June 1995, we evaluated retrospectively 96 consecutive
      patients who underwent the maze procedure (maze III) in combination with another
      type of cardiac operation. Four patients who died and 6 patients who required
      permanent pacemaker implantation because of sick sinus syndrome were excluded.
      Ambulatory electrocardiographic monitoring was evaluated 1 year after operation.
      Multiple logistic regression analysis was applied to identify the predictors of
      sinus rhythm restoration. RESULTS: The final population comprised 86 patients
      (mean age, 59.8 years; 67 patients with mitral valve disease). Overall, sinus
      rhythm was restored in 68 of 86 patients (79.1%). The magnitude of the atrial
      fibrillatory wave positively predicted postoperative sinus rhythm restoration.
      Conversely, left atrial diameter was inversely related to postoperative sinus
      rhythm restoration. The odds ratio of having both a fine atrial fibrillatory wave
      (< 1.0 mm) and enlarged left atrial diameter (> or = 65 mm) for patients with
      sinus rhythm restoration was 0.04 (95% confidence interval, 0.01 to 0.28).
      CONCLUSIONS: Atrial fibrillatory wave and left atrial diameter were independent
      predictors of sinus rhythm restoration after the maze procedure in patients with
      chronic atrial fibrillation and organic heart disease.

PMID- 9262583
TI  - Long-term follow-up (8 to 17 years) after thromboexclusion operation for thoracic
      aortic aneurysms.
AB  - BACKGROUND: It has been reported that the thromboexclusion operation is a good
      method for managing certain difficult thoracic aortic aneurysms. METHODS: Forty
      four patients underwent graft replacement (group 1) and 14, the thromboexclusion
      operation (group 2). We reviewed the long-term results of the thromboexclusion
      operation and compared them with those of graft replacement in our institutions.
      RESULTS: The hospital mortality rate in groups 1 and 2 was 29.5% (13 patients)
      and 35.7% (4 patients), respectively. In group 1, the one late death (2.3%) was
      due to heart failure and in group 2, three of the four late deaths (28.6%) were
      due to rupture of the excluded thoracic aorta, and one late death was due to
      heart failure. Long-term follow-up was possible for 23 patients in group 1 and 5
      patients in group 2. Survival 3 years after operation was significantly better in
      group 1 than in group 2 (p < 0.05). Long-term follow-up with blood pressure
      measurements, chest roentgenograms, electrocardiograms, and echocardiograms
      showed no significant differences between the preoperative and postoperative
      findings. However, in group 2, left ventricular hypertrophy and hypertension,
      which had not been present preoperatively, were found in all of the patients.
      Also, 1 patient has had persistent hemoptysis. CONCLUSIONS: The thromboexclusion
      operation has introduced unanticipated problems that were recognized at long-term
      follow-up.

PMID- 9262584
TI  - Delayed stimulation of the latissimus dorsi may result in disuse atrophy.
AB  - BACKGROUND: The latissimus dorsi is usually left unstimulated for 2 weeks after
      cardiomyoplasty to allow the muscle to recover from the loss of the collateral
      circulation. To determine whether the 2-week delay may cause muscle atrophy, we
      randomized 15 mongrel dogs to a control group or a disuse atrophy group. METHODS:
      The collateral circulation to the latissimus dorsi was ligated in all animals
      before cardiomyoplasty to reduce the risk of ischemic injury to the muscle during
      mobilization. Two weeks after collateral ligation, the atrophy group had the
      tendinous attachment of the latissimus dorsi severed and then 2 weeks later
      underwent cardiomyoplasty. The control group had a 2-week delay after collateral
      ligation followed by cardiomyoplasty. Biopsies were performed before collateral
      ligation and before cardiomyoplasty. After heart failure was induced, hemodynamic
      function was assessed during synchronized contraction of the latissimus dorsi by
      measuring the maximum systolic elastance, stroke volume, preload recruitable
      stroke work index, and diastolic compliance. RESULTS: Comparison of muscle
      morphology between the two groups demonstrated the presence of muscle atrophy in
      those animals that had been randomized to the atrophy protocol. During
      synchronized contraction of the latissimus dorsi, there was no significant
      increase in maximum systolic elastance in either group. However, both stroke
      volume and pulmonary recruitable stroke work index were significantly higher in
      the control animals during assisted beats. The left ventricle was less compliant
      in the atrophy group, suggesting that muscle atrophy had adversely affected
      diastolic function. CONCLUSIONS: Delayed electrical stimulation of the latissimus
      dorsi may result in atrophy and loss of function.

PMID- 9262585
TI  - Risk stratification for open heart operations: comparison of centers regardless
      of the influence of the surgical team.
AB  - BACKGROUND: Risk-adjusted mortality was previously used to compare institutions
      as a whole or surgeons. Because the same surgical team is working in two
      different hospitals, the aim of our study was to assess whether the institution
      can make a difference in surgical mortality. METHODS: Preoperative data of 554
      patients in institution A and 500 in institution B were prospectively collected
      during the same period of time. All patients were operated on by the same surgeon
      with the same first assistant and anesthesiology staff in both institutions.
      Patient population was stratified according to Parsonnet's predictive model, in
      five risk groups, and mortality was adjusted by the direct standardization
      method. RESULTS: At institution A it was observed that in-hospital mortality was
      2.3% (95% confidence interval, 1.3% to 4.0%), and in institution B 4.0% (95%
      confidence interval, 2.5% to 6.1%). The difference between the two mortality
      rates (1.7%; 95% confidence interval, -0.5% to 3.8%) is not statistically
      significant (p = 0.16), nor is the difference within each class. The standardized
      mortality ratio was 3.6% (95% confidence interval, 2.7% to 4.8%) and 5.8% (95%
      confidence interval, 4.6% to 7.2%), respectively. The difference of 2.2% (95%
      confidence interval, 0.5% to 3.8%) is statistically significant (p = 0.01).
      CONCLUSIONS: The institution can affect mortality of patients undergoing open
      heart operations, regardless of the influence of the surgical team.

PMID- 9262587
TI  - Long-term follow-up of small (size 20 and 21) Medtronic-Hall aortic valve
      prostheses.
AB  - BACKGROUND: Our goal was to study the long-term follow-up of patients having
      aortic valve replacement and to focus particularly on the patients receiving
      small prostheses. METHODS: Four hundred twenty-eight Medtronic-Hall valves were
      implanted (156 size 20 or 21 mm, 149 size 22 or 23 mm, and 123 size 25 or 27 mm).
      Group 20-21 had a higher number of female patients, more associated coronary
      lesions, and more patients with aortic stenosis. RESULTS: The actuarial survival
      rate at 8 years was 80% for group 20-21, 80% for group 22-23, and 76% for group
      25-27 (p = not significant). In group 20-21, the actuarial event-free rates at 8
      years were as follows: thromboembolic complications, 94%; prosthetic valve
      endocarditis, 99%; reoperation, 98%; and hemorrhagic complications, 78%. The only
      factors of prognostic value in this group were age and associated coronary
      lesions. CONCLUSIONS: The durable nature of the results obtained with the
      Medtronic-Hall 20- and 21-mm prostheses compared with large-diameter prostheses
      allows the use of a simple and reliable surgical technique and should mean that
      indications for ring enlargement become rare.

PMID- 9262588
TI  - Intraoperative blood flow measurement of the right gastroepiploic artery using
      pulsed Doppler echocardiography.
AB  - BACKGROUND: In coronary artery revascularization, the right gastroepiploic artery
      (GEA) has become the third arterial conduit of choice after both internal
      thoracic arteries. To evaluate the function of the right GEA, we used
      intraoperative ultrasonographic Doppler measurement of the blood flow of this
      artery. METHODS: From November 1992 to December 1993, in 41 consecutive patients,
      graft flow velocity, diameter, and blood flow were measured in the proximal part
      of the GEA before takedown and after completion of the anastomosis just before
      sternal closure. We also analyzed the predictors of postoperative ischemia.
      RESULTS: Flow volume of the GEA after anastomosis with the coronary artery has a
      significant correlation with the diameter of the target coronary artery (p =
      0.0011). Two patients had development of ischemia postoperatively. In both,
      volume flow of the GEA was less than 25 mL/min before takedown compared with an
      average flow of 55.78 mL/min in the patients without ischemia postoperatively.
      This was found to be a prognostic indicator of poor graft performance with
      consequent ischemia. CONCLUSIONS: When the GEA blood flow volume before takedown
      is less than 25 mL/min, we suggest that this artery not be used as a bypass graft
      for myocardial revascularization.

PMID- 9262586
TI  - L-arginine prevents cyclosporin A-induced pulmonary vascular dysfunction.
AB  - BACKGROUND: Cyclosporin A is known to alter endothelium-dependent responses to
      different agonists. Few data are available concerning the effect of cyclosporin A
      on the pulmonary vascular bed. METHODS: The endothelium-dependent responses to
      acetylcholine (20 micrograms), bradykinin (5 micrograms), and substance P (5
      micrograms) were investigated in a dog model of left lung autoperfusion at
      constant flow. RESULTS: The vasodilator response to bradykinin and substance P
      was significantly decreased with cyclosporin A (20 mg) administration. The
      average decreases in pulmonary arterial pressure with bradykinin were 5.4 +/- 1.5
      mm Hg and 2.4 +/- 0.4 mm Hg before and after cyclosporin A administration,
      respectively (p = 0.04). The average decreases in pulmonary arterial pressure
      with substance P were 4.4 +/- 1.0 mm Hg and 1.8 +/- 0.5 mm Hg before and after
      cyclosporin A administration, respectively (p = 0.04). The responses to
      acetylcholine and the endothelium-independent relaxing agent nitroglycerin were
      not significantly affected by cyclosporin A. The effects of cyclosporin A on
      endothelium-dependent responses to bradykinin and substance P were overcome by
      the administration of L-arginine (200 mg/kg intravenously). The decreased
      response to bradykinin and substance P after cyclosporin A administration was not
      significantly affected by indomethacin, a cyclooxygenase inhibitor. The pulmonary
      angiotensin-converting enzyme activity was also measured using [3H]benzoyl
      phenylalanyl-glycyl-proline, an inactive angiotensin-converting enzyme substrate.
      There was an average [3H]benzoyl-phenylalanyl-glycyl-proline hydrolysis of 54% +/
      2% and 55% +/- 2% before and after cyclosporin A administration, respectively
      (not significant). CONCLUSIONS: The present study suggests that cyclosporin A
      selectively decreases endothelium-dependent responses to bradykinin and substance
      P without affecting the cyclic guanosine monophosphate-dependent pathway in the
      canine pulmonary vascular bed. The decreased endothelium-dependent responses to
      bradykinin and substance P are not related to increased angiotensin-converting
      enzyme activity. The toxic effect of cyclosporin A on endothelium-dependent
      responses is reversible by the administration of L-arginine, a source of
      substrate for nitric oxide.

PMID- 9262589
TI  - Evaluation of brain oxygenation during selective cerebral perfusion by near
      infrared spectroscopy.
AB  - BACKGROUND: Although selective cerebral perfusion (SCP) has been used for
      cerebral protection in aortic arch operations, the appropriate perfusion
      conditions of SCP are unclear. METHODS: We used near-infrared spectroscopy, which
      evaluates brain ischemia noninvasively and continuously, to determine whether
      perfusion with SCP (core temperature, 20 degrees C; flow rate, 10 mL.kg-1.min-1)
      was acceptable in terms of oxyhemoglobin and deoxyhemoglobin in patients having
      SCP for aortic arch operations (SCP group, n = 6) versus patients having
      cardiopulmonary bypass (CPB) for coronary artery bypass grafting (CPB group, n =
      6). RESULTS: There were no significant differences in age (65 +/- 10 versus 63 +/
      12 years), CPB time (199 +/- 67 versus 199 +/- 52 minutes), changes in
      hematocrit (-12.9% +/- 3.7% versus -12.5% +/- 6.0%), lowest blood pressure (43 +/
      7 versus 45 +/- 10 mm Hg), or highest central venous pressure (8 +/- 2 versus 9
      +/- 4 mm Hg) between the SCP and CPB groups. In the SCP group, the maximum
      decrease in oxyhemoglobin level and the maximum increase in deoxyhemoglobin level
      were -5.0 to -11.4 mumol/L and -0.1 to 3.9 mumol/L, respectively; in the CPB
      group, the respective changes were -3.2 to -14.2 mumol/L and -0.4 to 3.6 mumol/L.
      Changes of oxyhemoglobin and deoxyhemoglobin levels in the SCP group were almost
      within the range of those in the CPB group. There were no brain complications in
      either group. CONCLUSIONS: As described here, SCP is acceptable and safe for
      brain protection in aortic arch procedures.

PMID- 9262590
TI  - Influence of left ventricular function on survival after coronary artery bypass
      grafting.
AB  - BACKGROUND: Preoperative left ventricular function is a most important predictor
      for survival in patients with ischemic heart disease. To elucidate the optimal
      timing of recommended coronary artery bypass grafting, we investigated the
      influence of different aspects of preoperative left ventricular function on
      relative survival. METHODS: To calculate the relative survival and estimate the
      disease-specific survival, we compared 6,514 patients who survived the first
      month after primary coronary artery bypass grafting with the general Swedish
      population stratified by age, sex, and 5-year calendar period. In particular we
      studied the relation between relative survival and different aspects of left
      ventricular performance, namely left ventricular function at rest, New York Heart
      Association functional class, and number of previous myocardial infarctions.
      RESULTS: The three variables (left ventricular function at rest, New York Heart
      Association functional class, and number of previous myocardial infarctions) as
      well as age and follow-up year gave independent information concerning relative
      survival. The results from this multivariate analysis were used to define a risk
      score for each patient. Patients were categorized into different risk groups.
      Patients in the low-risk group (30% of the total) showed a survival better than
      that of the population at large for 9 years after operation. The medium-risk
      group had no or low excess mortality for about 7 years, and the high-risk group
      (25%) showed increased excess mortality immediately after operation. CONCLUSIONS:
      If primary coronary artery bypass grafting is performed before the left
      ventricular function and physical performance deteriorate, survival is excellent.

PMID- 9262592
TI  - Modified T graft for triple-vessel disease.
AB  - BACKGROUND: Arterial coronary bypass grafts are used in younger patients due to
      the limited long-term patency of saphenous vein grafts. Using both internal
      thoracic arteries in a T graft configuration allows complete myocardial
      revascularization without the need for alternative conduit. METHODS: A
      prospective analysis of 75 consecutive patients with triple-vessel disease who
      were aged less than 66 years and who had a left ventricular ejection fraction
      greater than 0.50 was performed from November 1994 to November 1995. Seventy
      three patients underwent myocardial revascularization using a modified T graft
      technique using both internal thoracic arteries. Postoperative cardiac enzyme and
      electrocardiographic analyses were performed along with routine surgical and
      cardiologic review to March 1996. RESULTS: There were no deaths or perioperative
      myocardial infarcts, and there was no sternal dehiscence due to infection. Five
      patients had recurrent angina and underwent repeat angiography. Three were
      treated by single coronary artery angioplasty and 2 with medical therapy.
      CONCLUSIONS: A modified T graft revascularization of patients selected by the
      protocol used in this study is safe.

PMID- 9262591
TI  - Valve repair for mitral regurgitation caused by isolated prolapse of the
      posterior leaflet.
AB  - BACKGROUND: Although prolapse of the posterior leaflet is the most common
      abnormality of the mitral valve causing dysfunction, the long-term results of
      mitral valve repair for this condition are seldom reported. METHODS: From October
      1988 to June 1994, 208 patients (mean age, 59.4 years) with mitral regurgitation
      caused by isolated prolapse of the posterior leaflet underwent mitral valve
      repair alone or combined with myocardial revascularization (n = 30). The surgical
      techniques were quadrangular resection (n = 199) followed by annulus plication (n
      = 101) or sliding leaflet plasty (n = 98), use of artificial chordae (n = 5), or
      papillary muscle shortening (n = 4). All patients had an annuloplasty with a
      Carpentier ring. Mean follow-up was 3.4 +/- 0.1 years and total follow-up, 656
      patient-years. RESULTS: There were six operative deaths (2.9%). Postoperative
      Doppler echocardiography found two cases of systolic anterior motion (1%), and
      echocardiographic studies at follow-up showed satisfactory mitral valve function
      in 97% of 112 patients. At 6 years, the actuarial survival rate was 87% +/- 7%,
      and freedom from thromboembolic complications, bleeding complications, and
      reoperation was 93% +/- 7%, 95% +/- 3%, and 95% +/- 4%, respectively.
      CONCLUSIONS: Mitral valve repair for regurgitation caused by prolapse of the
      posterior leaflet provides excellent survival at 6 years and should be considered
      the method of choice for its surgical treatment.

PMID- 9262593
TI  - Aortic atheroma is related to outcome but not numbers of emboli during coronary
      bypass.
AB  - BACKGROUND: The relation between aortic atheroma severity and stroke after
      coronary artery bypass grafting is established. The relation between atheroma
      severity and other outcome measures or numbers of emboli has not been determined.
      METHODS: Using transesophageal echocardiography, we determined the severity of
      atheroma in the ascending, arch, and descending aortic segments in 84 patients
      undergoing operations. Seventy patients were monitored using transcranial Doppler
      ultrasonography. RESULTS: The incidence of stroke was 33.3% among 9 patients with
      mobile plaque of the arch and 2.7% among 74 patients with nonmobile plaque (p =
      0.011). Cardiac complications were not significantly related to atheroma severity
      in any aortic segment. Length of stay was significantly related to atheroma
      severity in the aortic arch (p = 0.025) and descending segment (p = 0.024). The
      presence of severe atheroma in both the arch and descending segments was
      associated with significantly longer hospital stays as compared with patients
      with severe atheroma in neither segment (p = 0.05). Numbers of emboli were
      greater in patients with severe atheroma at clamp placement, although the
      differences did not achieve statistical significance. CONCLUSIONS: Aortic
      atheroma severity is related to stroke and to the duration of hospitalization
      after coronary artery bypass grafting. The lack of correlation between numbers of
      emboli and atheroma severity suggests that m any emboli may be nonatheromatous in
      nature.

PMID- 9262594
TI  - Cardiopulmonary bypass alters vasomotor regulation of the skeletal muscle
      microcirculation.
AB  - BACKGROUND: Cardiopulmonary bypass (CPB) is associated with alterations in the
      regulation of organ perfusion and vascular permeability. The purpose of this
      study was to examine the effects of hypothermic CPB on the regulation of the
      skeletal muscle microcirculation and the modulating influence of the priming
      solution. METHODS: Sheep were placed on hypothermic CPB with a prime of either
      Pentastarch hydroxylethyl starch (HS) solution (n = 7), a solution in which HS is
      conjugated with deferoxamine (n = 7), or Ringer's lactate solution (n = 7). Sheep
      were placed on hypothermic CPB (27 degrees C) for 90 minutes while the heart was
      protected with cold blood cardioplegia. Sheep were then separated from CPB and
      perfused for an additional 3 hours off CPB. Hemodynamics and total water content
      were measured. RESULTS: In vitro relaxation responses of gracilis muscle
      arterioles (70 to 180 microns) to the endothelium-dependent agent acetylcholine,
      the endothelium-independent cyclic GMP-mediated vasodilator sodium nitroprusside,
      the beta-adrenergic agonist isoproterenol, and the adenylate cyclase activator
      forskolin were studied. No statistically significant hemodynamic differences were
      observed between groups. However, weight gain was significantly less when the
      priming solution was HS or HS-deferoxamine compared to when Ringer's lactate was
      used. Skeletal muscle arteriolar relaxations to the endothelium-dependent
      vasodilator acetylcholine and the beta-adrenergic agonist isoproterenol were
      impaired after CPB in the HS and Ringer's lactate groups. Acetylcholine response
      was preserved in the HS-deferoxamine group, whereas the response to isoproterenol
      remained impaired. The responses to sodium nitroprusside and forskolin were
      similar in all groups. CONCLUSIONS: Skeletal muscle microvascular endothelium
      dependent relaxation and beta-adrenergic relaxation are reduced after CPB using
      either a crystalloid or HS prime. Skeletal muscle microvascular endothelial
      dysfunction may be attributable to oxygen-derived free radical-mediated injury,
      whereas altered beta-adrenergic regulation is attributable to mechanisms other
      than the generation of oxygen-derived free radicals during CPB.

PMID- 9262595
TI  - Histologic analysis of transmyocardial channels: comparison of CO2 and
      holmium:YAG lasers.
AB  - BACKGROUND: Transmyocardial laser revascularization using different lasers is
      being tested in the treatment of refractory angina. We conducted comparative
      analysis of the acute and chronic myocardial effects of these different lasers.
      METHODS: Transmyocardial channels were made in normal dog hearts with either a
      holmium:yttrium-aluminum garnet or a CO2 laser. Channels were examined
      histologically 6 to 24 hours, 2 to 3 weeks, and 6 weeks after creation. RESULTS:
      Regardless of the laser source, the channels were occluded by thrombus within 6
      to 24 hours. Subsequently, organization and neovascularization of the channel
      region occurred. Thermoacoustic damage was initially greater with the
      holmium:yttrium-aluminum garnet laser, but the channel appearances were
      indistinguishable from those made with the CO2 laser by 6 weeks. CONCLUSIONS:
      Histologically, the myocardial effects of the CO2 and holmium:yttrium-aluminum
      garnet lasers are similar and differ predominantly in the amount of acute
      thermoacoustic injury. Channels are rapidly occluded by thrombus and are replaced
      by neovascularized collagen. This suggests that the physiologic effects of these
      two lasers may be similar and that mechanisms other than blood flow through
      chronic patent channels should be considered as contributing to the clinical
      benefits observed with this procedure.

PMID- 9262596
TI  - Impact of early exercise radionuclide cineangiography on long-term prognosis
      after CABG.
AB  - BACKGROUND: The immediate benefits of coronary artery bypass grafting might be
      only transient. This prospective study examined the capability of exercise
      radionuclide cineangiography done shortly after coronary artery bypass grafting
      to predict outcome and long-term prognosis. METHODS: Results of exercise
      radionuclide cineangiography at 5.5 +/- 0.7 months (range, 4 to 8 months)
      postoperatively were correlated with mortality, major surgical and nonsurgical
      cardiac events, and cardiac event-free survival in 100 consecutive patients who
      underwent coronary artery bypass grafting. Stepwise logistic regression analysis
      was used to evaluate the incremental value of radionuclide cineangiography beyond
      the commonly used variables. RESULTS: Left ventricular ejection fraction at rest
      was normal (> or = 0.45) in 72 patients and increased on exercise in 58. The
      exercise radionuclide variables that correlated with future cardiac events were
      change and fractional change in heart rate, ST segment changes, anginal pain and
      congestive heart symptoms during exercise, rest ejection fraction, and change and
      fractional changes in ejection fraction. Predictors of event-free survival were
      exercise heart rate, rest ejection fraction, and change and fractional change in
      ejection fraction during exercise. Logistic regression analysis revealed that
      change in ejection fraction was an independent predictor of cardiac death and
      surgical interventions, whereas resting ejection fraction was a predictor of
      nonsurgical cardiac events. CONCLUSIONS: Postoperative exercise radionuclide
      cineangiography carried out soon after coronary artery bypass grafting had
      definite independent prognostic value and should be performed routinely to help
      decide treatment protocol.

PMID- 9262598
TI  - Ross procedure with aortic root tailoring for aortic valve replacement in the
      pediatric population.
AB  - BACKGROUND: Aortic valve replacement with a pulmonary autograft (Ross procedure)
      is being applied more commonly in children. Although indications for this
      procedure have been expanded, the presence of a dilated aortic annulus has
      remained a relative contraindication. In this condition, the use of an undersized
      autograft in an enlarged aortic annulus may result in significant aortic
      regurgitation. METHODS: Among 68 children and young adults undergoing the Ross
      procedure, 15 (age range, 8 to 24 years) with severe aortic regurgitation or
      stenosis and an aortic annulus diameter that was at least 2 mm larger than the
      pulmonary annulus had aortic root tailoring. In this group, the diameter of the
      aortic annulus measured 26.6 +/- 1.3 mm (mean +/- standard error of the mean),
      whereas that of the pulmonary annulus was 22 +/- 0.9 mm. The mean annular
      difference was 4.6 +/- 0.7 mm (range, 2 to 12 mm). The aortic annulus was reduced
      by excising a triangular wedge of tissue posteriorly from the aortic valve
      annulus at the level of the commissure between the left and noncoronary cusps
      extending into the anterior leaflet of the mitral valve. The edges were
      reapproximated over a calibrated dilator to adjust the final size of the aortic
      annulus to 2 mm smaller than that of the pulmonary autograft. Circumferential
      felt strips were not used in any patient. RESULTS: All patients survived and
      morbidity was limited to one reoperation for bleeding. Doppler echocardiographic
      examination performed at discharge demonstrated that no patient had more than
      trace to 1+ aortic regurgitation and none had evidence of aortic stenosis. Over a
      mean follow-up period of 6.3 +/- 1.5 months (range, 1 to 16 months) there has
      been no late morbidity or mortality and no progression of aortic regurgitation.
      CONCLUSIONS: Aortic root tailoring further extends the use of the Ross procedure
      to patients with excessive aortic annular dilation while maintaining the
      potential for growth, which is particularly important in the pediatric
      population.

PMID- 9262597
TI  - Coronary artery bypass grafting "on pump": role of three-day discharge.
AB  - BACKGROUND: A new emphasis has been directed toward "off-pump" coronary artery
      bypass grafting to avoid the morbidity of cardiopulmonary bypass and further
      reduce the postoperative hospital length of stay. With the intent of achieving a
      hospital discharge for "on-pump" coronary artery bypass grafting procedures
      comparable with the same procedures "off pump," we applied a rapid-recovery
      protocol with particular attention paid to patients eligible for discharge on the
      third postoperative day. METHODS: The cases of 104 consecutive patients who
      underwent isolated coronary artery bypass grafting using cardiopulmonary bypass
      were retrospectively reviewed. A rapid-recovery protocol emphasizing reduced
      cardiopulmonary bypass time, an anesthesia protocol for early extubation,
      perioperative administration of corticosteroids and thyroid hormone, and
      aggressive diuresis was applied to all patients. The goal during the first 24
      hours postoperatively was to achieve early extubation as well as a mild state of
      negative fluid balance and to ensure absence of postoperative bleeding and a safe
      transfer from the intensive care unit to a monitored floor. On the second
      postoperative day, chest drains were discontinued, and aggressive ambulation
      therapy was instituted. If at 72 hours postoperatively the patient was walking
      without assistance, had return of normal bowel function, and had no atrial
      fibrillation, a 3-day discharge home was planned. RESULTS: The 30-day mortality
      rate for the entire group was 1.9%. The average postoperative hospital length of
      stay for the entire series was 4.8 +/- 2.4 days. Of the 102 survivors, 30
      patients (29%) were discharged within 3 days postoperatively (group 1), and 72
      patients (71%) were discharged after the third postoperative day (group 2).
      Patients in group 1 were younger and had fewer comorbid conditions. Compared with
      group 2, group 1 had fewer patients with diabetes (7% versus 28%; p < 0.05),
      congestive heart failure (7% versus 18%), symptomatic vascular disease (0% versus
      11%), chronic obstructive pulmonary disease (0% versus 10%), ambulatory
      difficulties (0% versus 10%), and the requirement of an intraaortic balloon pump
      preoperatively (13% versus 35%). Group 1 patients also had almost no
      complications and a lower readmission rate (3.3% versus 6.9%). CONCLUSIONS: With
      the application of a rapid-recovery protocol to patients undergoing "on-pump"
      coronary artery bypass grafting, discharge home within 3 days postoperatively is
      attainable and safe for patients who have minimal comorbid conditions.

PMID- 9262599
TI  - Anatomically sound, simplified approach to repair of "complete" atrioventricular
      septal defect.
AB  - BACKGROUND: There are few congenital anomalies of the heart that have benefited
      more from thorough anatomic analysis than the complex anomaly known as
      atrioventricular septal defect in the setting of common atrioventricular
      junction. Recent advances in understanding the anatomy of this lesion have led to
      alternative methods of repairing these defects. METHODS: The medical records of
      21 consecutive patients undergoing repair of complete atrioventricular septal
      defect have been reviewed. Nine of these patients had a standard one- or two
      patch repair, and 12 had direct closure of the ventricular element of the defect.
      RESULTS: Direct closure resulted in significantly shorter pump and cross-clamp
      times. Follow-up for an average of 34 months suggests that when direct closure
      can be performed, the results are comparable with those of the more standard
      technique. CONCLUSIONS: Our initial success with this approach is encouraging;
      however, longer follow-up is required to establish whether it will be broadly
      applicable.

PMID- 9262600
TI  - Senning plus arterial switch operation for discordant (congenitally corrected)
      transposition.
AB  - BACKGROUND: Congenitally corrected transposition of the great arteries is a
      complex cardiac lesion, usually associated with ventricular septal defect, left
      ventricular outflow tract obstruction, and tricuspid valve abnormalities. A
      subset of patients without left ventricular outflow tract obstruction have
      undergone Senning plus arterial switch operation in an attempt to place the left
      ventricle in the systemic circuit and the right ventricle in the pulmonary
      circuit. METHODS: Fourteen patients have had the operation performed since July
      1989. Age and weight medians were 12 months (range, 0.5 to 120 months) and 8.2 kg
      (range, 3.2 to 34 kg). All but 1 patient had a left ventricular to right
      ventricular pressure ratio greater than 0.7, due to a large ventricular septal
      defect (with or without a previous pulmonary artery band), severe congestive
      heart failure caused by right ventricular dysfunction and tricuspid
      insufficiency, or a pulmonary artery band for left ventricular retraining. At
      least 10 patients had strong contraindications to "classic" repair, including
      right ventricular hypoplasia (n = 2), moderate to severe right ventricular
      dysfunction (n = 5), or moderate to severe tricuspid insufficiency (n = 9).
      RESULTS: There was one hospital death, occurring in a neonate (7%; 95% confidence
      interval = 0% to 34%). Actuarial survival beyond 10 months is 81% (95% confidence
      interval = 42% to 95%), currently with 389 patient-months of total follow-up
      time. The median grade of tricuspid insufficiency fell from 3/4 preoperatively to
      1/4 postoperatively (p = 0.003). Right ventricular function is normal in 11/12
      current survivors, all but 1 of whom are in New York Heart Association class I or
      II. CONCLUSIONS: Senning plus arterial switch operation is a good option for
      selected patients with congenitally corrected transposition of the great arteries
      with a similar or lower early risk (as compared with classic repairs). Some of
      the long-term problems associated with congenitally corrected transposition of
      the great arteries may be avoided with this strategy.

PMID- 9262601
TI  - Arch growth after staged repair of interrupted aortic arch using carotid artery
      interposition.
AB  - BACKGROUND: Between 1980 and 1990, our practice was to perform carotid artery
      interposition as part of a staged repair of interrupted aortic arch with various
      associated cardiac defects. METHODS: This procedure was used in 16 patients with
      IAA type B. The median age at operation was 4.5 days and the median weight, 3.2
      kg. Ten of the patients had an associated ventricular septal defect. Six more had
      complex anatomy. There were two death at carotid interposition, two interim
      deaths, and two deaths after intracardiac repair. Preoperative echocardiographic
      and angiographic studies were compared with postoperative studies in 11 survivors
      of arch repair to assess sequential growth of the interposed carotid artery.
      Measurements of the carotid artery were normalized to the descending aorta.
      RESULTS: Preoperatively, the left carotid artery had a median diameter of 3.7 mm
      and was 42.9% of the descending aortic diameter. Postoperative studies performed
      at a median age of 5.7 months disclosed that the interposed carotid artery had
      grown to a median diameter of 7.0 mm and was 69.6% of the diameter of the
      descending aorta (normal > or = 81%). On follow-up at a median time of 4 years, 6
      of 9 patients have no gradient by blood pressure measurements or
      echocardiographic Doppler studies, and 3 have modest gradients. No patient has
      required revision of the arch repair. CONCLUSIONS: Survival is good after carotid
      artery interposition for interrupted aortic arch and growth of the carotid artery
      approaches that of a normal arch. Carotid artery interposition is a viable
      alternative for repair of this lesion should primary definitive repair not be
      feasible.

PMID- 9262602
TI  - Patch augmentation of regurgitant common atrioventricular valve in univentricular
      physiology.
AB  - BACKGROUND: Regurgitation of the common atrioventricular valve in patients with
      univentricular atrioventricular connection has a negative impact on outcome in
      the Fontan operation. Because severe regurgitation of the common atrioventricular
      valve may not be sufficiently reduced by a volume-reducing operation alone, the
      addition of a valvuloplasty may be a necessary adjunct to achieve competence of
      the common atrioventricular valve. A modified technique of valvuloplasty of the
      common atrioventricular valve and its medium-term results are presented. METHODS:
      Two infants and 1 young child with isomeric right atrial appendages, complete
      atrioventricular canal, univentricular atrioventricular connection with a double
      inlet right ventricle through a common atrioventricular valve, pulmonary atresia
      (n = 2) or pulmonary stenosis (n = 1), and bilateral superior venae cavae
      presented with marked dilatation of the annulus of the common atrioventricular
      valve and severe regurgitation between the bridging leaflets. All 3 patients
      previously had been palliated with a generous central aortopulmonary shunt. The
      repair technique consisted of patch augmentation of the central bridging leaflets
      with an autologous pericardial patch. In addition, bilateral bidirectional
      cavopulmonary anastomoses were constructed and additional sources of pulmonary
      blood flow were eliminated. RESULTS: Intraoperative echocardiography demonstrated
      competence of the large central leaflet, excellent coaptation between the central
      leaflet and the bilateral mural leaflets, and decrease of the anteroposterior
      diameter of the annulus of the atrioventricular valve from 24, 29, and 34 mm
      preoperatively to 20, 23, and 29 mm, respectively. In all 3 patients,
      echocardiographic follow-up at 17, 14, and 6 months showed continued competence
      of the atrioventricular valve. CONCLUSIONS: Pericardial patch augmentation of the
      bridging leaflets may be a valuable adjunctive technique in the reconstruction of
      the regurgitant common atrioventricular valve in hearts with univentricular
      atrioventricular connection, especially if a volume-reducing operation alone does
      not result in competence of the valve.

PMID- 9262603
TI  - Morphologic features of the normal aortic arch in neonates, infants, and children
      pertinent to growth.
AB  - BACKGROUND: The aorta in newborns rapidly adapts by growth to postnatal
      circulatory conditions. The question arises what structural features are
      associated with growth and whether differences occur between the various
      segments. METHODS: Nineteen specimens have been studied: seven from babies less
      than 1 month, seven from 1 month to 1 year, and five from 1 to 4 years. In each
      baby the diameter of the aortic segments and its branches were measured.
      Histologically the number of elastin lamellae was counted, and furthermore,
      collagen density was quantified at several measurement sites. RESULTS: The
      diameter of each segment increases rapidly after birth and more so than that of
      the descending aorta, except for the brachiocephalic artery and its branches and
      the left common carotid artery, albeit not at the same rate. The ascending aorta
      is the only segment that shows a decrease in the ratio of elastin lamellae to
      diameter. Collagen density was always highest in the descending aorta.
      CONCLUSIONS: These observations show that postnatal growth of the thoracic aorta
      is associated with distinct structural remodeling soon after birth; these
      observations are of clinical relevance in case of aortic arch abnormalities.

PMID- 9262604
TI  - Hypoplastic aortic arch morphology pertinent to growth after surgical correction
      of aortic coarctation.
AB  - BACKGROUND: Whether a hypoplastic transverse arch will grow after successful
      coarctectomy remains controversial. METHODS: We studied 15 coarctation specimens
      with hypoplastic transverse arch. Eight patients were less than 1 month old and 7
      were between 1 and 3 months. The diameter and length of the various segments of
      the aortic arch were measured. The number of elastin lamellae was determined
      histologically. Collagen density was quantified with a microdensitophotometer.
      Using immunohistochemistry, we determined alpha-actin-positive smooth muscle
      cells in the media of the ascending aorta and the hypoplastic transverse arch.
      RESULTS: Despite a hypoplastic transverse arch, the ascending and descending
      aorta grew. The absolute number of elastin lamellae in the hypoplastic transverse
      arch was low, but when expressed as a ratio versus its diameter, this number was
      high (p < 0.05). Collagen density showed high absolute values in the descending
      aorta. In the older group, 4 of 7 showed no staining for alpha-actin in the
      hypoplastic transverse arch, whereas under 1 month of age, only 2 of 8 cases were
      negative. CONCLUSIONS: The hypoplastic transverse arch is characterized by a
      relatively high number of elastin lamellae. Fewer alpha-actin-positive cells in
      the hypoplastic transverse arch occur in older specimens, which could indicate a
      diminished potential growth.

PMID- 9262605
TI  - Modified ultrafiltration after cardiopulmonary bypass in pediatric cardiac
      surgery.
AB  - BACKGROUND: Cardiopulmonary bypass in children results in considerable water
      retention, especially in neonates and small infants. Dilution of plasma proteins
      increases water loss into the extravascular compartments. Excessive total body
      water may prolong ventilatory support and may contribute to a prolongation of
      intensive care convalescence. After discontinuation of cardiopulmonary bypass,
      modified ultrafiltration can be used to withdraw plasma water from the total
      circulating volume. METHODS: This retrospective study included 198 pediatric
      patients who underwent cardiac operations in the period from September 1991 to
      November 1994. Two groups were compared: 99 patients without ultrafiltration and
      99 patients receiving modified ultrafiltration. The following indices were
      analyzed: cardiopulmonary bypass prime volume, transfused blood volume during and
      after the operation, postoperative chest drain loss, and hemoglobin and
      hematocrit levels before, during, and after the procedure. RESULTS: Modified
      ultrafiltration resulted in a significant increase in hemoglobin and hematocrit
      levels and a significantly lower amount of transfused blood. Mean postoperative
      chest drain loss was significantly less in the patients who underwent modified
      ultrafiltration. CONCLUSIONS: Modified ultrafiltration decreases blood
      transfusion requirements and chest drain loss after pediatric cardiac surgical
      procedures.

PMID- 9262606
TI  - Pulmonary valve replacement late after repair of tetralogy of Fallot.
AB  - BACKGROUND: Pulmonary valve incompetence is usually well tolerated after
      tetralogy of Fallot repair but may result in late progressive right heart failure
      as manifested by increasing fatigue, dyspnea, and frequently arrhythmias.
      METHODS: All patients who underwent pulmonary valve replacement in our center
      late after repair of tetralogy of Fallot were reviewed. RESULTS: Eighty-five
      patients had elective pulmonary valve replacement late (median, 9.3 years) after
      repair. Operative risk was low (1.1%). Ninety percent of survivors are in New
      York Heart Association class I. Survival 10 years after pulmonary valve
      replacement is 95%, with 86% of the patients free of reoperation for valve
      failure. CONCLUSIONS: Pulmonary valve replacement is infrequently required after
      repair of tetralogy of Fallot. Pulmonary valve replacement may be performed
      electively with little risk; it improves symptoms of right heart failure and
      provides satisfactory long-term survival with low risk of early valve failure. As
      the population of patients who have had repair of tetralogy of Fallot ages,
      pulmonary valve replacement will become a more frequent consideration.

PMID- 9262607
TI  - Homograft as a conduit for superior vena cava syndrome.
AB  - This report outlines the management of a 30-year-old man with severe
      multiresistant mycobacterium tuberculosis of his right lung. Despite medical
      therapy he had open tuberculosis with positive sputum smears. A right
      pneumonectomy was undertaken, but due to distorted hilar anatomy, the superior
      vena cava was resected. Postoperatively, superior vena cava syndrome developed
      and failure of venous drainage was demonstrated by bilateral arum venography and
      computed tomographic scanning. The superior vena cava syndrome was successfully
      relieved using an aortic homograft as a superior vena cava replacement instead of
      a spiral vein graft or a prosthetic conduit.

PMID- 9262608
TI  - Coronary artery problems during homograft aortic valve replacement: role of
      transesophageal echocardiography.
AB  - We describe 2 cases in which intraoperative transesophageal echocardiography
      detected complications related to the proximal coronary arteries during homograft
      aortic valve and root replacement. In both cases, cardiopulmonary bypass could
      not be discontinued despite the use of large doses of inotropic drugs.
      Transesophageal echocardiography demonstrated aliasing on color flow mapping in
      the left main coronary artery in 1 case and proximal right coronary artery in the
      other, along with severely depressed left ventricular anterior wall and right
      ventricular function, respectively. Coronary artery bypass grafting was performed
      in both cases, and the outcome was successful.

PMID- 9262609
TI  - Thrombus formation on a calcific and severely stenotic bicuspid aortic valve.
AB  - We report on a case of thrombus formation on a native bicuspid aortic valve,
      which was found during an elective operation for aortic valve replacement.
      Although no apparent predisposing cause of thrombosis could be ascertained,
      severe calcific stenosis of the bicuspid valve and cardiac catheterization may
      have played a role. The patient is in excellent condition 9 months after the
      operation.

PMID- 9262610
TI  - Bilateral branch pulmonary artery obstruction due to kinking at insertion sites
      of bilateral ductus arteriosus.
AB  - Bilateral ductus arteriosus (or ligamentum arteriosum) with right aortic arch and
      isolation of the left subclavian artery is a rare anomaly of the aortic arch
      system. We report on a patient with complete atrioventricular septal defect,
      right aortic arch, bilateral ligamentum arteriosum, and isolation of the left
      subclavian artery in whom kinking at the ductal insertions caused bilateral
      branch pulmonary artery obstruction. Complete surgical repair was performed when
      the patient was 4 months of age, and the pulmonary artery obstructions were
      entirely relieved by ligation and division of both ducts without pulmonary
      arterioplasty.

PMID- 9262611
TI  - Absorbable pulmonary artery band.
AB  - Absorbable pulmonary artery banding may be a useful method of avoiding further
      operation or angioplasty in patients whose underlying lesion has a natural
      history of resolution. We report 2 cases of absorbable pulmonary artery banding
      using braided Dexon. In both cases the bands functioned well initially and were
      completely resorbed after 2 years and 6 months, respectively.

PMID- 9262612
TI  - Right atrial separation for chronic atrial fibrillation with atrial septal
      defects.
AB  - A right atrial separation procedure was performed for the ablation of atrial
      fibrillation during the concomitant repair of an atrial septal defect. This
      procedure consisted of a Y-shaped incision in the right atrium, followed by
      cryoablation of the tricuspid annulus and the atrial septum without any
      procedures performed on the left atrium. This is a simple and effective method
      for the elimination of chronic atrial fibrillation associated with atrial septal
      defects in adults.

PMID- 9262613
TI  - Internal mammary artery grafting in a neonate for coronary hypoperfusion after
      arterial switch.
AB  - Coronary hypoperfusion may occur after the arterial switch operation, especially
      when coronary anatomy is complicated. We report successful use of the left
      internal mammary artery graft for a neonate with coronary hypoperfusion after the
      arterial switch operation for transposition of great arteries with intramural
      left coronary artery. Internal mammary arteriography showed a patent graft 19
      months after operation.

PMID- 9262614
TI  - Minimally invasive coronary bypass for protected left main coronary stenosis
      angioplasty.
AB  - A case is presented of left main coronary artery stenosis in a patient with
      significant comorbidities who was successfully managed with minimally invasive
      direct coronary artery bypass as protection before percutaneous transluminal
      coronary angioplasty. This "hybrid" approach for the management of a high-risk
      patient led to a favorable outcome.

PMID- 9262615
TI  - Elephant trunk reconstruction for aberrant right subclavian and aortic aneurysm.
AB  - Although an aberrant right subclavian artery is the most common abnormality of
      aortic arch development, it is an unusual entity to encounter during repair of
      thoracic aortic aneurysms. A case of an aberrant right subclavian artery
      requiring reattachment during repair of an ascending aorta, aortic arch, and
      descending thoracic aortic aneurysm is reported. We report using the modified
      elephant trunk technique for surgically managing the aneurysm and aberrant right
      subclavian artery.

PMID- 9262616
TI  - Simultaneous surgical correction of a common atrium and impure flutter.
AB  - We performed surgical correction and treatment of a common atrium and chronic
      impure flutter using a computerized mapping system in a 49-year-old man. A
      reentrant circuit was observed to exist around the left atrial appendage. In
      contrast to the regular activation in the left atrium, the activation sequence of
      the right atrium was extremely chaotic. Cryolesions were applied to the area of
      the reentrant pathway. After the operation, sinus rhythm was restored.

PMID- 9262617
TI  - Surgical management of intrapericardial teratoma diagnosed in utero.
AB  - Intrapericardial teratoma is a rare, often benign congenital tumor, which
      frequently leads to respiratory distress and pericardial tamponade shortly after
      birth. Surgical excision is not only curative but potentially lifesaving, because
      these lesions often become fatal if not promptly excised. We present a case of
      one of two twins diagnosed with a large intrapericardial teratoma. The management
      of this case was complicated by the necessity to consider the well-being of the
      other (normal) twin in planning the timing of delivery and operation. After the
      twins were delivered by cesarean section in one operating room, the mass was
      excised from the infant in an adjoining operating room with cardiopulmonary
      bypass standby.

PMID- 9262619
TI  - Simultaneous repair of pectus excavatum and congenital heart disease.
AB  - Most repair of heart lesions and pectus deformity has been performed in adult
      patients using long incisions, sternal splits, excision of deformed cartilages,
      and sternal turnover operations that could result in poor cosmesis and chest
      growth in children because of sternal devascularization. We performed
      simultaneous pectus repair and atrial septal defect closure in 2 children using a
      short longitudinal incision and avoiding a transverse or longitudinal sternal
      split. After extraperichondrial excision of the deformed cartilages and
      mobilization of the sternum from the neurovascular bundles, a transverse wedge of
      sternum was removed at the level of the third cartilages, allowing cephalad
      retraction of the sternum and providing excellent exposure for the intracardiac
      operation. The cosmetic appearance remains excellent in both patients at 1 and 4
      years postoperatively.

PMID- 9262618
TI  - Dramatic response of postthymomectomy myasthenia gravis with multiple lung
      nodules to corticosteroids.
AB  - A 36-year-old woman underwent thymomectomy and left pneumonectomy with total
      pleurectomy for stage IVa invasive thymoma without myasthenia gravis. Six years
      later, a crisis of myasthenia gravis developed associated with multiple lung
      nodules. Steroid therapy induced remarkable regression of the lung nodules that
      has persisted for more than 11 months. Concurrently, the clinical severity of her
      myasthenia gravis markedly decreased and recovered to the extent of permitting
      her to return to normal life.

PMID- 9262621
TI  - Combined repair of upper sternal cleft and tetralogy of Fallot in an infant.
AB  - We report on a 2-month-old infant with the unusual association of an upper
      sternal defect and tetralogy of Fallot. Surgical correction of the cardiac
      disease consisted of closing the ventricular septal defect and relief of the
      right ventricular outflow tract by infundibuloplasty. The already less compliant
      bony thorax of the infant made direct approximation of the upper sternal defect
      only possible with adjuvant bilateral chondrotomies. Sternal cleft repair is
      advised during the very first weeks of life, during which complete correction of
      the rarely associated tetralogy of Fallot can be successfully performed.

PMID- 9262620
TI  - Chronic expanding hematoma in the chest.
AB  - We herein report the successful surgical treatment of 2 cases of chronic
      expanding hematoma in the chest. The first patient, who had undergone
      thoracoplasty 42 years earlier due to tuberculosis, became aware of a slowly
      growing mass protruding in the lateral thoracic wall. The second patient, who had
      tuberculous pleurisy 36 years earlier, was referred to our department because of
      a slowly expanding intrathoracic mass revealed by a roentgenogram. The tumors,
      which were encapsulated chronic hematomas, were both surgically resected. These
      cases are rare because of the development of a very large mass after undergoing
      treatment for tuberculosis more than 30 years previously.

PMID- 9262622
TI  - Placement of two pacing leads with one venipuncture in dual-chamber pacemaker
      implantation.
AB  - We describe a method of inserting two guidewires through a single percutaneous
      introducer and then subsequently sliding the introducer over each guidewire
      separately to provide independent access for transvenous placement of two pacing
      leads.

PMID- 9262623
TI  - Prevention of internal thoracic artery spasm.
AB  - Perioperative spasm of the internal thoracic artery is a common experience in
      coronary artery bypass grafting. We describe a simple method of harvesting the
      internal thoracic artery with improved ease of dissection that helps to prevent
      the arterial spasm.

PMID- 9262624
TI  - Thoracic aortic operations: management of maldistribution of arterial flow during
      cardiopulmonary bypass.
AB  - On three occasions during operations for aortic aneurysm involving the ascending
      aorta it was noted that upon the release of the aortic clamp the grafted segment
      remained collapsed, indicating very little or no flow reaching the lumen of the
      reconstructed aorta. This was promptly and successfully remedied in 2 patients by
      perfusing the graft directly with a pediatric arterial catheter attached to a
      pump head while the femoral arterial line maintained systemic arterial inflow.
      This simple, safe, and highly effective technique adds to the surgeon's
      repertoire to manage yet another intriguing intraoperative development during
      thoracic aortic operations.

PMID- 9262625
TI  - Modified unroofing procedure in anomalous aortic origin of left or right coronary
      artery.
AB  - A modified technique is reported for unroofing of the intramurally coursing
      segment of the left main or right coronary artery with anomalous aortic origin.
      This technique avoids detachment and resuspension of the intercoronary commissure
      and thus lessens the risk of post-operative aortic valve regurgitation.

PMID- 9262626
TI  - Cardiac stabilizer for minimally invasive direct coronary artery bypass.
AB  - We describe a simple and effective device that is useful in reducing cardiac
      motion, enabling the surgeon to perform a precise direct left internal mammary
      artery anastomosis to the left anterior descending coronary artery on a beating
      heart.

PMID- 9262628
TI  - As originally publised in 1989: Right thoracotomy, femorofemoral bypass, and deep
      hypothermia for re-replacement of the mitral valve. Updated in 1997.

PMID- 9262627
TI  - Magnesium deficiency and cardiogenic shock after cardiopulmonary bypass.
AB  - Magnesium is an important cation that has a key role in cellular processes of
      energy transfer and utilization involving adenosine triphosphate, and influences
      cell membrane functions. Its antiarrhythmic properties are well-known and it is
      widely recognized as an adjunct for the treatment of arrhythmias after myocardial
      infarction and cardiopulmonary bypass. Magnesium may influence hemodynamic
      performance through its effects on vascular tone, modulation of intracellular
      calcium, regulation of catecholamine activity, and its essential role in
      adenosine triphosphate metabolism. The potential for magnesium deficiency to
      affect cardiovascular performance may be especially relevant in ischemic states.
      We report a case of cardiogenic shock developing after cardiopulmonary bypass
      that was initially unresponsive to therapeutic intervention, but that resolved
      promptly after magnesium administration. The potential role of magnesium in
      enhancing hemodynamic performance is discussed, with a review of its cellular
      metabolic properties and activities.

PMID- 9262629
TI  - Tetraplegia after tracheal resection.

PMID- 9262631
TI  - Thoracoscopic thymectomy: which side to approach?

PMID- 9262630
TI  - Pulmonary resection after pneumonectomy.

PMID- 9262632
TI  - Pulmonary artery aneurysm.

PMID- 9262634
TI  - Aneurysm of pulmonary trunk.

PMID- 9262635
TI  - Risk of bacteremia complicating valve replacement in the presence of colon
      cancer.

PMID- 9262636
TI  - Adenosine and K(+)-induced Ca2+ loading.

PMID- 9262637
TI  - Acute adrenal insufficiency after coronary artery bypass grafting.

PMID- 9262638
TI  - The safety of CABG without cardiopulmonary bypass.

PMID- 9262639
TI  - Emergency coronary bypass on a beating heart.

PMID- 9262640
TI  - Talc insufflation versus slurry.

PMID- 9262641
TI  - Aortic approach to retained mitral leaflet after mitral valve replacement.

PMID- 9262642
TI  - Synthesis of dipeptides by suspension-to-suspension conversion via thermolysin
      catalysis: from analytical to preparative scale.
AB  - When using proteases in direct reversal of their normal hydrolytic function, the
      equilibrium position is very important in limiting the attainable yield in
      equilibrium-controlled enzymic peptide synthesis. Analysis of the equilibrium
      position reveals a favourable shift towards the peptide product if starting
      materials are largely undissolved in the reaction medium and the product
      precipitates. This approach enabled us to obtain high peptide yields in
      thermolysin-catalysed reactions in high-density aqueous media with an equimolar
      supply of substrates. The easy scale-up (up to mol-scale) of this approach is
      demonstrated by two examples. Z-His-Phe-NH2 and Z-Asp-Phe-OMe, precursors for
      cyclo-[-His-Phe-] and the low-calorie sweetener Aspartame, respectively, were
      synthesized in preparative yields of 84-88%.

PMID- 9262643
TI  - Application of reversible biotinylated label for directed immobilization of
      synthetic peptides and proteins: isolation of ligates from crude cell lysates.
AB  - Chaperonin 10 protein from Rattus norvegicus (Rat cpn 10) has been reported to
      bind chaperonin 60 from Escherichia coli (GroEL) in an ATP-dependent manner.
      Chemically synthesized Rat cpn10 was immobilized in a defined orientation to
      agarose-bound monomeric avidin using a reversible biotinylated affinity label
      (1), attached to the N alpha-terminal residue. The resulting affinity
      chromatographic matrix was then used to isolate binding proteins from a crude
      cell lysate. Following affinity separation the bound ligand and ligate was
      released by treatment with organic base. Rat cpn 10 was prepared using a highly
      effective synthetic protocol involving HBTU/HOBt activation and capping with N-(2
      chlorobenzyloxycarbonyloxy) succinimide to terminate unreacted amino groups. The
      biotinylated Fmoc-based molecule (1) was introduced specifically onto the N alpha
      terminal amino acid as the succinimidyl carbonate, before final cleavage and
      deprotection of side-chain protecting groups using a low-TFMSA/high-HF procedure.
      Crude biotinylated Rat cpn10 (Rat cpn10 + 1) was immobilized on monomeric avidin
      with a binding efficiency of approximately 75% and unlabelled truncated/capped
      impurities eluted off the column with buffer. The biotinylated Rat cpn10-avidin
      affinity matrix was then used to isolate GroEL from a crude cell lysate. The
      identity of the purified protein was confirmed by SDS-PAGE and binding to a
      specific anti-GroEL monoclonal antibody (MoAb). These results extend the
      applicability of the biotinylated label (1), providing a reversible non-covalent
      anchor for immobilization of peptide and protein ligands, thus simplifying
      isolation of ligates and enabling recovery of synthetic material under mild
      conditions.

PMID- 9262644
TI  - Solid-phase acyl donor as a substrate pool in kinetically controlled protease
      catalysed peptide synthesis.
AB  - Recently we have demonstrated the advantage of solid-phase substrate pools mainly
      in equilibrium controlled protease-catalysed peptide syntheses. The extension of
      this approach to protease-catalysed acyl transfer reactions will be presented.
      The model reaction was systematically investigated according to both the
      influence of solid phases present in the system on enzyme activity as well as
      nucleophile concentration on peptide yield. The key parameter for obtaining high
      peptide yield via acyl transfer is the ratio between aminolysis and hydrolysis.
      We combined high nucleophile concentrations with solid-phase acyl donor pools.
      This approach enabled us to supply ester substrate and nucleophile in equimolar
      amounts in a high-density media without the addition of any organic solvent.
      Several multi-functional di- to tetrapeptides were obtained in moderate to high
      yields.

PMID- 9262645
TI  - Molecular parameters in melittin immunogenicity.
AB  - Based on immunogenicity studies, two T-cell epitopes in melittin were found to be
      functional in guinea pigs, one being centrally located, the other one residing in
      the C-terminal chain. In Balb/c mice only the central epitope was found to be
      active. A human T-cell clone was found by T-cell proliferation studies to employ
      strictly the C-terminal chain. Truncation of melittin peptides at the N-terminus
      did not markedly affect the capacity of guinea pigs to develop anti-IgG responses
      towards peptidic epitopes and towards a C-terminally attached haptenic group.
      Attachment of various substituents inside and outside the T-cell epitopic areas
      had no marked effect on antibody responses. In contrast, the substituents
      positioned within a T-cell epitope abolished T-cell proliferation. This
      difference between whole animal data and cellular in vitro responses is presently
      not understood.

PMID- 9262646
TI  - Synthesis of a novel side-chain to side-chain cyclized enkephalin analogue
      containing a carbonyl bridge.
AB  - A novel type of cyclic opioid peptide analogue, cyclo[N epsilon,N epsilon'
      carbonyl-D-Lys2,Lys5]enkephalinamide, was prepared from a linear precursor
      peptide. The peptide was synthesized on the Merrified resin and also by a
      combination of the solid-phase technique and the classical method in solution. In
      both cases the cyclization was performed by reaction of bis(4
      nitrophenyl)carbonate with the free side-chain amino groups of the two lysine
      residues. The described method permits the convenient preparation of novel
      peptide analogues cyclized via a ureido group incorporating the side-chain amino
      groups of two alpha, omega-diamino acid residues. The cyclic enkephalin analogue
      containing a 21-membered ring structure showed preference for mu over delta
      opioid receptors in opioid bioassays in vitro.

PMID- 9262647
TI  - A novel beta-thymosin from the sea urchin: extending the phylogenetic
      distribution of beta-thymosins from mammals to echinoderms.
AB  - The study of the phylogenetic distribution of the beta-thymosin family is
      important to elucidate its biological function further. A new thymosin,
      designated as thymosin beta 14, consisting of 40 amino acid residues and with a
      molecular weight of 4537 Da as determined by ion spray mass spectrometry, was
      isolated from the sea urchin. The N-terminus of this polypeptide is blocked by an
      acetyl group as found by matrix-assisted laser desorption mass spectrometric and
      amino acid analysis. The primary structure was elucidate by Edman degradation of
      the HPLC-purified thymosin beta 14 fragments produced by digestion with
      endoproteinase Asp-N and trypsin. Sequence comparison reveals that thymosin beta
      14 is 73% homologous to thymosin beta 4, obtained from calf thymus. By isolating
      and characterising the structure of thymosin beta 14 from the sea urchin, an
      invertebrate, substantial knowledge about the phylogenetic distribution and
      evolution of beta-thymosins is gained.

PMID- 9262648
TI  - Synthesis and properties of novel lipopeptides and lipid mimetics.
AB  - Lipid mimetics, synthetic molecules that resemble natural lipids either
      structurally or functionally, have been developed as potential medicinal
      substances. They have been successfully applied in the development of drug and
      peptide delivery systems and for the development of inhibitors or lipid
      metabolizing enzymes. Phospholipase A2 is considered to be involved as the rate
      limiting step in the production of lipid mediators of inflammatory responses and,
      as such, it has been a target for drug design. A series of lipid mimetics
      including lipopeptides, amides and alcohols of lipidic alpha-amino acids, have
      been tested by bulk and monolayer assay techniques. The findings suggested the
      direct interaction of the tested compounds with porcine pancreatic phospholipase
      A2. The inactivation of the enzyme occurred in a competitive manner. The most
      active compound I (2-amino-N-hexadecyl-L-hexanamide) showed an apparent IC50 of
      12 microM and inhibitory power Z = 13 in the monolayer assay.

PMID- 9262649
TI  - Structural comparison in solution of a native and retro peptide derived from the
      third helix of Staphylococcus aureus protein A, domain B: retro peptides, a
      useful tool for the discrimination of helix stabilization factors dependent on
      the peptide chain orientation.
AB  - A peptide fragment corresponding to the third helix of Staphylococcus Aureus
      protein A, domain B, was chosen to study the effect of the main-chain direction
      upon secondary structure formation and stability, applying the retro-enantio
      concept. For this purpose, two peptides consisting of the native (Ln) and
      reversed (Lr) sequences were synthesized and their conformational preferences
      analysed by CD and NMR spectroscopy. A combination of CD and NMR data, such as
      molar ellipcitity. NOE connectivities, H alpha and NH chemical shifts, 3J alpha N
      coupling constants and amide temperature coefficients indicated the presence of
      nascent helices for both Ln and Lr in water, stabilized upon addition of the
      fluorinated solvents TFE and HFIP. Helix formation and stabilization appeared to
      be very similar in both normal and retro peptides, despite the unfavourable
      charge-macrodipole interactions and bad N-capping in the retro peptide. Thus,
      these helix stabilization factors are not a secondary structure as determined for
      this specific peptide. In general, the synthesis and confirmational analysis of
      peptide pairs with opposite main-chain directions, normal and retro peptides,
      could be useful in the determination of secondary structure stabilization factors
      dependent on the direction.

PMID- 9262651
TI  - Annual author and subject indexes to volumes 459, 474-481 (January 1993, January
      December 1994).

PMID- 9262650
TI  - 3D structure of kaliotoxin: is residue 34 a key for channel selectivity?
AB  - Kaliotoxin (KTX) is a natural peptide blocker of voltage-dependent K+ channels.
      The 3D structure of a truncated analogue of KTX (Fernandez et al. (1994)
      Biochemistry 33, 14256-14263) was determined by NMR spectroscopy and showed
      significant differences from structures established for other related scorpion
      toxins. A recent publication with the structure of the complete toxin (Aiyar et
      al. (1995) Neuron 15, 1169-1181) did not confirm these differences. In this
      communication we report NMR data for KTX at pH 3.0, 5.5 and 7.2 and the 3D
      structure obtained from data at pH = 5.5. Complete KTX displays a folding similar
      to that of other toxins with an alpha-helix and a beta-sheet linked by two
      disulphide bonds. The pKa of His 34 is anomalously low (4.7-5.2 depending on the
      buffer) owing to its interaction with two Lys residues (including the essential
      Lys 27), the charged N-terminus and the side chain of Met 29. Charged residues
      are placed symmetrically with respect to an axis that approximately coincides
      with one of the principal components of the moment of inertia of the toxin. His
      34, which occupies a well-defined position between two conserved Cys, is located
      on the centre of a layer of charged groups. Positively and negatively charged
      residues are found at the same position in related toxins. It is suggested that
      electrostatic effects modulate the distances between positive charges in flexible
      side chains, contributing to the fine tuning of the selectivity toward different
      channel subclasses and that the approximate coincidence between the moment of
      inertia and the charge axis facilitate the approach of the toxin to the channel.
      The very low pKa of His 34 implies that it will be completely unprotonated at
      physiological pH.

PMID- 9262652
TI  - FARAD seeks more funds.

PMID- 9262653
TI  - Scientists to pursue AIDS vaccine based on EIA model.

PMID- 9262654
TI  - AVMA, OSHA meet and establish dialogue.

PMID- 9262655
TI  - Sarcoma brochure available from AVMA.

PMID- 9262656
TI  - FDA prohibits extralabel use of two drug classes.

PMID- 9262657
TI  - Take your hamburger's temperature.

PMID- 9262658
TI  - USDA plans for BSE contingency.

PMID- 9262659
TI  - Plan put to test.

PMID- 9262660
TI  - CVM lifts import alert on FSH products.

PMID- 9262662
TI  - Is advanced training in veterinary medicine worth the cost?

PMID- 9262661
TI  - Plague finding ways to stop a killer.

PMID- 9262663
TI  - Confusion on ethical guidelines.

PMID- 9262664
TI  - What is your diagnosis? Hepatomegaly and cholelithiasis with mineralization of
      the biliary tract.

PMID- 9262666
TI  - Some legal concerns of veterinary medical associations.

PMID- 9262665
TI  - Chronic weight loss in an immunodeficient adult llama.

PMID- 9262667
TI  - Extralabel use of tranquilizers and general anesthetics.

PMID- 9262668
TI  - Knowledge and attitudes of residents in two areas of Massachusetts about rabies
      and an oral vaccination program in wildlife.
AB  - OBJECTIVE: To compare public knowledge and attitudes about rabies and an oral
      rabies vaccination program in raccoons. DESIGN: Random-digit dial telephone
      survey. SAMPLE POPULATION: Residents of 2 areas of Massachusetts. PROCEDURE:
      Residents of 2 areas of Massachusetts were called to participate in a telephone
      survey. One area (Cape Ann) included 8 towns, most of which have had rabies in
      raccoons since 1993. The second area (Cape Cod) included 7 towns, 5 of which have
      not had rabies in raccoons. Calls were made to 642 persons, and of these, 265
      agreed to participate in the survey. Of the nonrespondents who were subsequently
      contacted again, half agreed to participate. Data were analyzed using a
      statistical program. Fisher's exact and chi 2 tests were used to determine
      associations. RESULTS: Residents from the area virtually free of rabies in
      raccoons were significantly less likely to consider rabies as a potential health
      threat for children in their household. The perception of rabies as a threat was
      higher for residents in the endemic area. Residents in both areas considered
      rabies control to be a high priority and supported use of state funding for an
      oral vaccination program. CLINICAL IMPLICATIONS: People recognize dangers
      associated with rabies and believe that oral vaccination programs will decrease
      the risk of exposure.

PMID- 9262669
TI  - Use of propofol-isoflurane as an anesthetic regimen for cesarean section in dogs.
AB  - OBJECTIVE: To evaluate use of propofol-isoflurane as an anesthetic regimen for
      cesarean section in dogs and to compare this protocol with epidural analgesia and
      anesthesia induced with thiopental sodium. DESIGN: Prospective study. ANIMALS:
      141 bitches admitted for cesarean section. PROCEDURE: General anesthesia was
      induced with propofol in 141 dogs undergoing cesarean section. After intubation,
      anesthesia was maintained by means of inhalation of isoflurane (0.5 to 2.0%),
      administered in a 65:35 mixture of oxygen:nitrous oxide. After induction, 20
      minutes were allowed to elapse before delivery of puppies was begun. Viability of
      neonates was ascertained immediately after surgery. Owners were interviewed by
      telephone to determine survival of puppies during the postoperative period.
      Survival rates from this study were compared with those from cesarean section
      performed on dogs under epidural analgesia or under general anesthesia induced
      with thiopental sodium. RESULTS: Induction, maintenance, and recovery were
      problem free in all bitches. Of 412 puppies delivered by cesarean section, 293
      (71%) survived, 13 (3%) were born alive but died within 20 minutes of delivery,
      and 106 (26%) were stillborn. Survival rate for puppies from dams induced with
      propofol-isoflurane was similar to that for puppies from dams receiving epidural
      analgesia. Survival rate for puppies delivered by cesarean section performed on
      dams under general anesthesia was higher for dams induced with propofol than for
      dams induced with thiopental sodium. CLINICAL IMPLICATIONS: General anesthesia
      induced with propofol and maintained with isoflurane is acceptable for performing
      cesarean section in dogs.

PMID- 9262670
TI  - Colonic nitrite and immunoglobulin G concentrations in dogs with inflammatory
      bowel disease.
AB  - OBJECTIVE: To evaluate lavage analytes as markers of mucosal inflammation in
      healthy dogs and dogs with inflammatory bowel disease (IBD). DESIGN: Case control
      study. ANIMALS: 9 healthy dogs and 10 dogs with IBD. PROCEDURE: A polyethylene
      glycol electrolyte solution was administered into the dogs colons via a rectal
      balloon catheter prior to colonoscopy. Lavage solution was allowed to remain
      intraluminally for 30 minutes and then was withdrawn. Lavage supernatant samples
      were immediately analyzed for total protein, IgG, and nitrite concentrations and
      myeloperoxidase activity. Mucosal biopsy specimens were obtained from the
      descending colon and histologically reviewed. RESULTS: All dogs with IBD had mild
      to severe lymphocytic-plasmacytic colitis, whereas 8 of 9 healthy dogs did not
      have substantial mucosal inflammation. Myeloperoxidase activity was not detected
      in lavage samples from healthy dogs or dogs with IBD. Total protein concentration
      was not significantly different between groups. Mean nitrite and IgG
      concentrations were significantly higher in samples from dogs with IBD (1.83
      nmol/ml and 46 mg/dl, respectively), compared with samples from healthy dogs
      (0.245 nmol/ml and undetectable concentrations, respectively). Severity of
      lesions was not correlated with nitrite or IgG concentration. CLINICAL
      IMPLICATIONS: Assay of nitrite and IgG concentrations in colonic lavage fluid is
      a simple, objective means of evaluating mucosal inflammation in dogs with IBD.
      Potential uses include monitoring response to treatment and evaluation of complex
      cases of chronic intestinal inflammation.

PMID- 9262671
TI  - Comparison of results of adrenocorticotropic hormone stimulation and low-dose
      dexamethasone suppression tests with necropsy findings in dogs: 81 cases (1985
      1995).
AB  - OBJECTIVE: Comparison of diagnostic accuracy of results of low-dose dexamethasone
      suppression (LDDS) and ACTH stimulation tests with necropsy findings in 81 dogs.
      DESIGN: Retrospective study. ANIMALS: 81 dogs that had undergone screening tests
      for hyperadrenocorticism and that had a complete necropsy report. PROCEDURE:
      Medical records were evaluated for results of CBC, serum biochemical analysis,
      urinalysis, endocrine testing, signalment, treatment, and necropsy findings. Each
      dog was definitively classified as having true-positive, true-negative, false
      positive, or false-negative results. Statistical analyses included determination
      of prevalence, apparent prevalence, accuracy, number of dogs misclassified,
      sensitivity, specificity, and positive- and negative-predictive values. RESULTS:
      Of the 81 dogs that fit the criteria for selection, 40 (49%) were confirmed as
      having hyperadrenocorticism (30 had pituitary-dependent disease and 10 had
      adrenal gland tumors). Forty-one dogs had illnesses attributable to a cause other
      than disease of the adrenal glands. Sensitivity of ACTH stimulation and LDDS
      tests were 95 and 96%, respectively. Specificity for the ACTH stimulation test
      was higher (91%) than that of the LDDS test (70%). When prevalence of the disease
      in the study population was taken into consideration, the positive-predictive
      value for the ACTH stimulation test was 91%, compared with 76% for the LDDS test.
      CLINICAL IMPLICATIONS: The ACTH stimulation test was more specific than the LDDS
      test, although sensitivity was similar for both tests. The ACTH stimulation test
      also had a significantly higher positive-predictive value than the LDDS test when
      a prevalence of 25% was taken into consideration.

PMID- 9262672
TI  - Insulin overdose in dogs and cats: 28 cases (1986-1993).
AB  - OBJECTIVE: To characterize the frequency, medical history, clinical signs,
      methods of treatment, and outcome of insulin-induced hypoglycemia and to identify
      predisposing factors. DESIGN: Retrospective study. ANIMALS: 8 dogs and 20 cats
      with diabetes mellitus that developed hypoglycemia because of insulin overdose.
      PROCEDURE: Medical records of dogs and cats receiving insulin for treatment of
      diabetes mellitus were reviewed. Medical records of dogs and cats that had an
      episode of hypoglycemia were reviewed in detail. RESULTS: Overdosing of insulin
      was more common in cats than in dogs. Median weight of diabetic cats that became
      hypoglycemic was significantly greater than that of the hospital population of
      diabetic cats at diagnosis. Eighty percent of cats that became hypoglycemic were
      receiving insulin doses > 6 U/injection, administered once or twice daily. Dose
      and type of insulin did not correlate with duration or severity of hypoglycemia.
      In 7 of 8 dogs and 10 of 20 cats, management factors or concurrent medical
      problems were considered to be predisposing causes for insulin overdose. Two dogs
      and 2 cats did not have clinical signs of hypoglycemia, despite documented low
      concentrations of glucose in their blood. CLINICAL IMPLICATIONS: Diabetic cats,
      especially if obese, are at greater risk of insulin overdose than are diabetic
      dogs. The reason for overdose may not be evident. Diabetic dogs and cats may
      become hypoglycemic without developing autonomic warning signs of hypoglycemia,
      or these signs may not be recognized (hypoglycemia unawareness).

PMID- 9262673
TI  - Sepsis of the common digital extensor tendon sheath secondary to
      hemicircumferential periosteal transection in a foal.
AB  - A 4-month-old Quarter Horse was admitted for evaluation of infection that
      developed following bilateral hemicircumferential periosteal transection and
      elevation. Sepsis of the common digital extensor tendon sheath was diagnosed.
      Treatment included lavage of the tendon sheath, placement of an indwelling drain
      for lavage after surgery, establishment of drainage, and administration of
      antimicrobial and anti-inflammatory drugs. Three months after treatment, the foal
      was clinically normal.

PMID- 9262674
TI  - Overwhelming strongyloidosis in a foal.
AB  - A 6-month-old foal was evaluated because of weakness, weight loss, and
      inappetence of 3 weeks' duration. On initial examination, the foal was weak,
      poorly responsive, and emaciated. Clinicopathologic abnormalities included anemia
      and hypoproteinemia. Because of its severe debilitation, the foal was
      euthantized. Necropsy revealed marked infection of the small intestine with
      Strongyloides westeri and severe edema of the entire gastrointestinal tract. The
      foal had been orphaned when it was 6 hours old and raised in isolation from other
      horses. We believe that this foal developed overwhelming strongyloidosis when it
      was first exposed to other foals at 5 months of age, because it had not been
      naturally exposed to the organism at a younger age and was immunologically naive.

PMID- 9262675
TI  - Surgical treatment of progressive ethmoidal hematoma aided by computed tomography
      in a foal.
AB  - A progressive ethmoidal hematoma (PEH) was treated successfully in a 4-week-old
      Belgian filly by surgical removal, using a frontonasal bone flap. The filly had
      respiratory stridor, epistaxis, and facial enlargement over the left paranasal
      sinuses, which had progressively increased in size since birth. Computed
      tomographic images of the head obtained with the foal under general anesthesia
      were useful in determining the extent and nature of the soft-tissue mass and
      planning surgical intervention. On the basis of the histologic appearance of the
      mass, a diagnosis of PEH was made. Twelve months after surgery, the facial
      appearance was normal and the abnormal appearance of the ethmoid region on
      endoscopic evaluation was less obvious, with return of the nasal septum to a
      normal position. Progressive ethmoidal hematoma is uncommon and, to our
      knowledge, has not been reported in a neonate. Clinical signs of PEH in this foal
      were atypical because of the rapid enlargement of the mass, extent of facial
      deformity, and minimal epistaxis and interoperative hemorrhage.

PMID- 9262676
TI  - Lateral buccotomy for removal of a supernumerary cheek tooth in a horse.
AB  - A 3-year-old female Standardbred was admitted for evaluation of a firm swelling
      on the right side located rostral to the facial crest and a firm intraoral
      swelling located rostral to the erupted cheek teeth. Examination of skull
      radiographs revealed a supernumerary cheek tooth rostral to the erupted third
      premolar. The supernumerary tooth was removed via lateral buccotomy. The horse
      did not have complications after surgery and resumed racing. Lateral buccotomy
      should be considered for removal of rostrally located maxillary or mandibular
      cheek teeth. Supernumerary cheek teeth can be found in locations in the upper
      dental arcade, other than caudal to the last molar.

PMID- 9262679
TI  - Computed tomography of the normal feline nasal cavity and paranasal sinuses.
AB  - Computed tomography (CT) images of the feline nasal cavity and paranasal sinuses
      were acquired from normal adult cats. Good resolution and anatomic detail were
      obtained from the CT images using soft tissue formatting. A description of normal
      feline nasal cavity and paranasal sinus anatomy using CT is presented.

PMID- 9262677
TI  - Neodymium:yttrium-aluminum-garnet laser treatment of cystic granula iridica in
      horses: eight cases (1988-1996).
AB  - OBJECTIVE: To determine clinical features of cystic granula iridica in horses and
      outcome of horses treated with an ophthalmic neodymium:yttrium-aluminum-garnet
      (Nd:YAG) laser. DESIGN: Retrospective study. ANIMALS: 8 horses. PROCEDURE: An
      ophthalmic Nd:YAG laser was used to deflate cysts in all horses. RESULTS: Horses
      were examined because of visual impairment (n = 5), decreased jumping performance
      (2), or head shaking (1). Clinical signs associated with cysts resolved in all
      horses after treatment. Short- and long-term complications did not develop, and
      cysts did not recur. CLINICAL IMPLICATIONS: Cystic granula iridica may cause
      vision impairment in horses. Treatment with an ophthalmic Nd:YAG laser appears to
      be safe and effective.

PMID- 9262680
TI  - Thoracic radiographic findings in dogs infected with Rickettsia rickettsii.
AB  - Sixteen beagle dogs were injected intradermally with Rickettsia rickettsii. The
      dogs were divided into four groups (n = 4): 1) infected, non-treated control; 2)
      infected, treated with doxycycline; 3) infected, treated with doxycycline and an
      anti-inflammatory dose of corticosteroid; and 4) infected, treated with
      doxycycline and an immunosuppressive dose of corticosteroid. Thoracic radiographs
      were made and ocular fluorescein angiography was performed on days 6, 10, 17 post
      inoculation. A mild interstitial lung opacity was noted in 4/16 dogs on day 6,
      5/16 on day 10 and 3/16 on day 17 post-inoculation. Increased retinal vascular
      permeability was noted in 8/16 dogs on day 6, 3/16 on day 10 and 1/16 on day 17
      post-inoculation. Correlation between the presence of radiographic and retinal
      lesions was not significant (p = 0.08). Eleven, naturally infected, dogs with
      thoracic radiographs and a final diagnosis of RMSF were also evaluated. Four of
      the 11 dogs had an unstructured interstitial pattern. Dogs with acute,
      experimentally-infected or naturally-occurring RMSF may have subtle pulmonary
      changes characterized by an unstructured interstitial pattern.

PMID- 9262681
TI  - Subdural injection of contrast medium during cervical myelography.
AB  - Three patients (1 dog, 2 horses) are described where myelography was complicated,
      purportedly by injection of contrast medium into the meninges superficial to the
      subarachnoid space. Contrast medium injected in this location in a cadaver tended
      to accumulate dorsally within the vertebral canal, deep to the dura mater but
      superficial to the subarachnoid space. The ventral margin of the pooled contrast
      medium had a wavy or undulating margin and the dorsal margin was smooth. Pooled
      contrast medium was believed to be sequestered within the structurally weak dural
      border cell layer between the dura mater and arachnoid membrane, or the so-called
      subdural space.

PMID- 9262682
TI  - Correlation of radiographic, necropsy and histologic findings in 8 dogs with
      elbow dysplasia.
AB  - Elbow dysplasia is osteoarthrosis/degenerative joint disease due to abnormal
      development of the elbow joint. The abnormal development is the result of
      specific inherited etiologies alone or in combination. This paper attempts to
      clarify the diagnosis of elbow dysplasia based on the presence of degenerative
      joint disease by correlating radiographic, necropsy, and histopathologic results
      using elbows from 8 German Shepherd dogs. All elbows had radiographic changes
      consistent with osteoarthrosis/degenerative joint disease which were identified
      best on the flexed medial-lateral projection. Radiographically, a specific
      diagnosis was made in seven elbows; ununited anconeal process (6) and
      osteochondrosis (1). At necropsy these lesions were confirmed plus 14 elbows were
      identified that had fragmented medial coronoid process (6), abnormally shaped
      medial coronoid processes or fissures in the articular cartilage of the medial
      coronoid process (8). Additionally, histopathologically there was proliferative
      synovitis at the radial notch of the ulna and degenerative changes on the
      proximal, nonarticular surface of the anconeal process at the site of insertion
      of the olecranon ligament and joint capsule. Therefore, for screening the elbow
      joint to identify elbow dysplasia, the recognition of osteoarthrosis/degenerative
      joint disease on an extreme flexed mediolateral radiograph appears to be
      sufficient.

PMID- 9262683
TI  - Diagnosis of cerebral ventriculomegaly in normal adult beagles using quantitative
      MRI.
AB  - The brain of 17 asymptomatic normal adult beagles was evaluated with magnetic
      resonance imaging. Lateral ventricular size was quantified using computer
      algorithms. In beagles with large ventricles, contrast medium was introduced into
      the cerebellomedullary cistern to determine whether obstructive hydrocephalus was
      present. Total lateral ventricular volume ranged from 77 mm3 to 11,726 mm3. Based
      on Gd-DTPA diffusion, the CSF flow pattern was considered normal and normal
      neural morphology was seen using electron microscopy. Results suggest a high
      incidence of clinically asymptomatic ventriculomegaly in normal adult beagles.

PMID- 9262684
TI  - Radiology corner. Sagittal computed tomography of the feline spine.

PMID- 9262685
TI  - Asystole associated with iohexol myelography in a dog.
AB  - This is a report of a 10-year-old female neutered Doberman Pinscher with a
      clinical diagnosis of myelopathy. The dog was anesthetized using oxymorphone,
      thiopental, and halothane in oxygen for a cerebrospinal tap and a myelogram.
      Iohexal injection into the subarachnoid space by lumbar puncture was uneventful.
      Additional iohexal was given into the cerebeliomedullary cistern. Immediately
      following iohexal administration into the cerebellomedullary cistern, several
      electrocardiographic changes occurred. Two extended periods of asystole responded
      to intravenous glycopyrrolate administration. A slow multiform ventricular escape
      rhythm was established after the second dose of glycopyrrolate. Ultimately,
      atrial activity with apparent AV dissociation resumed, atrial fibrillation
      developed, and the rhythm converted to normal sinus rhythm. The dog had a normal
      cardiac examination the following day. Two days later, the dog was anesthetized
      using a similar anesthetic regimen with maintenance on isoflurane in oxygen for a
      hemilaminectomy. The dog recovered uneventfully from surgery and was discharged 2
      days later.

PMID- 9262686
TI  - Biplane transesophageal echocardiography in the normal cat.
AB  - Eight healthy, adult cats were examined with biplane transesophageal
      echocardiography (TEE). Cats were sedated with a combination of diazepam and
      propofol and were examined using a 5 mm x 80 cm pediatric biplane TEE probe.
      Consistent images were obtained at three imaging depths within the esophagus. The
      caudal position provided satisfactory short-axis images of the left ventricle and
      heart base. The middle position provided the best long-axis views of the left
      atrium, left ventricle, and aorta and allowed Doppler examination of transmitral
      left ventricular inflow. The cranial position provided satisfactory imaging of
      the aorta and pulmonary artery and allowed Doppler examination of right
      ventricular and left ventricular outflow. Biplane TEE provides an additional
      method of imaging the feline heart which is complimentary to other imaging
      techniques and the images obtained were similar to those reported for dogs.
      Although TEE offers a slight advantage over transthorcic imaging for Doppler
      examination, the quality of the images of heart base structures was not as
      consistently superior to transthoracic images in cats as reported in dogs.

PMID- 9262687
TI  - Ultrasonographic features of intestinal adenocarcinoma in five cats.
AB  - Adenocarcinoma, followed by lymphosarcoma, are the most common feline intestinal
      neoplasms. Clinicopathological, survey radiographic, and ultrasonographic
      findings of five cats with intestinal adenocarcinoma are reported. An abdominal
      mass was palpable in all five cats, but the mass could be localized to bowel in
      only two cats. Radiographically an abdominal mass was detected in only one cat.
      Ultrasonographically there was a segmental intestinal mural mass in all five
      cats. The mass was characterized by circumferential bowel wall thickening with
      transmural loss of normal sonographic wall layers. In one cat, the
      circumferential symmetric hypoechoic bowel wall thickening was similar to that
      reported for segmental lymphoma. In the other four cats, the sonographic features
      of the thickened bowel wall were varied, being mixed echogenicity and asymmetric
      in 3 cats and mixed echogenicity and symmetric in one. The results of the present
      report suggest that sonographic observation of mixed echogenicity segmental
      intestinal wall thickening in the cat represents adenocarcinoma rather than
      lymphosarcoma, although other infiltrative diseases should be considered.

PMID- 9262688
TI  - Ultrasonography of gastric ulceration in the dog.
AB  - The clinical, ultrasonographic and, when available, histopathologic findings of
      gastric ulceration in 7 dogs were reviewed. The most common clinical signs were
      vomiting, hematemesis, melena, weight loss and anemia. Ultrasonographic features
      of gastric ulcer included local thickening of the gastric wall, possible loss of
      the 5-layer structure, the presence of a wall defect or "crater," fluid
      accumulation in the stomach and diminished gastric motility. The localized
      gastric thickening varied from 9 to 16 mm. The ulcer crater was often located in
      the center of the thickened site and appeared as a mucosal defect associated with
      persistent accumulation of small echoes, most likely representing microbubbles.
      In this preliminary study, there was no definitive ultrasonographic distinction
      between benign and malignant ulcers.

PMID- 9262689
TI  - Color flow Doppler imaging and Doppler spectral analysis of the brain of neonatal
      dogs.
AB  - Doppler ultrasonography was performed on the cerebral arteries of 19 neonatal
      dogs. Vascular structures were identified using anatomic preparations of brains
      pre-injected with a radiopaque silicone rubber product and cleared using a
      modified tissue clearing technique. Brain sections were subsequently radiographed
      or examined under a stereomicroscope. Color flow Doppler imaging was used to
      facilitate positioning of the Doppler calipers for measurement of peak systolic
      velocity, minimum diastolic velocity, and resistance index. Blood flow velocities
      in the internal carotid and middle cerebral arteries were lower when measured in
      transverse images than in sagittal images. The rostral cerebral arteries could be
      measured using either plane but values obtained from different locations or using
      different methods of measurement were statistically different. Blood flow
      velocities generally increased during the first month after birth. Arterial
      signals were diphasic with flow throughout diastole. Resistance indices most
      often were between 0.6 and 0.7 and did not exceed 0.86.

PMID- 9262690
TI  - Quantitative 99mTc-pertechnetate thyroid scintigraphy in normal beagles.
AB  - This study was done to investigate the validity of published canine
      thyroid/salivary (T/S) ratios of approximately 1 in normal dogs and to determine
      thyroid uptake of 99mTc-pertechnetate (pertechnetate) measured as percent uptake
      of injected dose. These parameters were evaluated in 13 Beagle dogs over a 4 hour
      period. Mean +/- standard deviation (SD) and median T/S ratios of 1.2 +/- 0.3 and
      1.1 were essentially the same at twenty minutes and 1 hour. T/S values ranged
      from 0.9 to 2.2 at 20 minutes and from 0.8 to 2.4 at 1 hour. T/S ratio values
      progressively declined over the subsequent time intervals with mean +/- SD and
      median values of 0.6 +/- 0.2 and 0.6, respectively, measured at 4 hours. The mean
      +/- SD maximum percent dose uptake of pertechnetate within the thyroid gland was
      0.55% +/- 0.15% with a range of 0.28% to 0.90%. The mean +/- SD time interval
      from injection of pertechnetate to maximum uptake within the thyroid gland was
      160 +/- 55 minutes with a range 31-240 minutes. The data derived from this study
      of normal dogs may be useful in the evaluation of dogs with thyroidal diseases
      including hypothyroidism.

PMID- 9262691
TI  - The role of the emergency department in creating a safe America.

PMID- 9262692
TI  - Rural hospital transfer patterns before and after implementation of a statewide
      trauma system. OHSU Rural Trauma Research Group.
AB  - OBJECTIVE: To evaluate trauma transfer practices in rural Oregon before and after
      implementation of a statewide trauma system. METHODS: A pre- vs post-system
      implementation (historical control) analysis of trauma transfer practices was
      performed using a sample of rural ED trauma patients from 4 Level-3 and 5 Level-4
      trauma hospitals. Medical records of patients with specific index injury
      diagnoses in 4 anatomic regions (head, chest, liver/ spleen, and femur/open
      tibia) were reviewed for a 3-year period before statewide trauma system
      implementation and 3 years after hospital trauma designation. RESULTS: Of 1,057
      patients entered into the database, 532 were evaluated during the pre-system
      period and 525 were evaluated during the post-system period. Overall, 47% had
      head injuries, 34% had chest injuries, 23% had femur/open-tibia injuries, and 12%
      had spleen/liver injuries. There were 142 (13%) patients with an injury in > 1
      index area. After trauma system implementation, there was a significant increase
      in the proportion of ED trauma patients transferred from Level-4 trauma hospitals
      (32% vs 68%, p < 0.001), with a corresponding decrease in the number of hospital
      admissions to these facilities (63% to 29%, p < 0.001). Significant increases in
      the proportion transferred from Level-4 trauma hospital EDs were noted for all
      index injury categories (p < 0.001). Trauma patients presenting to Level-4 EDs
      were significantly more likely to be transferred to Level-2 facilities (66% vs
      82%, p = 0.030), while patients at Level-3 facilities were significantly more
      likely to be transferred to Level-1 centers (2% vs 14%, p = 0.002) following
      trauma system implementation. Multiple logistic regression modeling indicated
      that implementation of the statewide trauma system was an independent predictor
      of rural trauma patient transfer from Level-4 hospitals, while transfers from
      Level-3 facilities were dependent on type of injury. CONCLUSION: Implementation
      of the Oregon statewide trauma system was associated with a redistribution of
      rural trauma patients to trauma hospitals with greater therapeutic resources.

PMID- 9262693
TI  - The urban epidemiology of recurrent injury: beyond age, race, and gender
      stereotypes.
AB  - OBJECTIVES: To profile all patients presenting to an urban ED with any injury,
      and to determine whether the rate of subsequent injury treated in the ED varied
      by demographic and E-code (external mechanism of injury) category. The hypothesis
      that young black males were disproportionately at risk for re-injury was
      addressed. METHODS: A cohort of consecutive patients presenting to an urban ED
      with any injury between January 1, 1991, and November 31, 1992, were followed
      prospectively for 1 year from their index visit dates. Any repeat ED visits due
      to injury were sought. The mean number of injury visits per year (the total
      number of ED injury visits for each patient divided by 1 year) was computed for
      the overall population and by race, age, gender, and E-code. RESULTS: The sample
      consisted of 34,378 patients who made 44,813 visits to the ED for injury. Of
      these patients, 22% had a repeat injury in 1 year, with a cohort mean of 1.30
      injury visits per year. This mean did not vary appreciably by race (black 1.33,
      white 1.27), age (1-17 yr, 1.21; 18-24 yr, 1.32; 25-64 yr, 1.34; > 65 yr, 1.23),
      gender (males 1.33, females 1.27), or E-code category. Having a prior injury
      visit in the preceding year was the best predictor of future injury (mean repeat
      visit rate = 2.08). CONCLUSIONS: When examining patients presenting with any
      injury to an urban ED, the mean numbers of injury visits are remarkably similar
      across demographic and E-code categories. Although there are factors that place
      patients at risk for recurrent injury, those factors are not demographic-all
      patients presenting to an ED with injury should be considered at risk for re
      injury.

PMID- 9262694
TI  - Ankle radiograph utilization after learning a decision rule: a 12-month follow
      up.
AB  - OBJECTIVE: To test whether the reduction in ankle radiograph ordering was
      sustained during a 12-month period after a formal trial to introduce the Ottawa
      ankle rules. METHODS: A before-after clinical trial of ankle radiograph ordering
      practice was performed in a university-based ED. All 1,884 (947 "during
      intervention," 937 "postintervention") adults seen with acute ankle injuries
      during 2 12-month trial periods were evaluated. The behavioral intervention was
      the teaching of the Ottawa ankle rules and feedback of compliance with the rules
      during the intervention period. No further education about the ankle rules or
      feedback regarding compliance occurred during the postintervention year.
      Physicians were unaware of any postintervention surveillance. The primary outcome
      was the proportion of eligible patients referred for an ankle radiograph during
      the intervention and postintervention periods. RESULTS: During the intervention
      period (January 1-December 31, 1993), the proportion of patients who received an
      ankle radiograph [609 x-rayed of 947 patients seen (64.3%; 95% CI 61.2-67.4%)]
      did not differ from the proportion who received an x-ray in the postintervention
      period (January 1-December 31, 1994) [583 x-rayed of 937 patients seen (62.2%;
      95% CI 59.1-65.3%), p = 0.65, power > 0.80 to detect a 10% increase in the
      radiograph ordering rate]. There was also no difference in the radiograph
      ordering rate in the first 3 months of the postintervention period compared with
      the last 3 months of the postintervention period (68.8% vs 64.7%, respectively, p
      > 0.30). CONCLUSIONS: Compliance with the Ottawa ankle rules was sustained during
      a 12-month postintervention surveillance period when physicians did not know they
      were being observed. Physicians will continue to use a simple clinical guideline
      once it has been learned.

PMID- 9262695
TI  - Effectiveness of selective use of intravenous pyelography in patients presenting
      to the emergency department with ureteral colic.
AB  - OBJECTIVE: To determine whether i.v. pyelography (IVP) is required routinely for
      all patients presenting to the ED with ureteral colic. METHODS: A randomized
      prospective study was conducted with 2 patient group-a routine IVP group, in
      which all patients underwent IVP, and a selective IVP group, in which patients
      were treated, observed, and released without undergoing IVP unless they
      experienced continued symptoms. The study was performed in a large university
      affiliated, community hospital ED. Participants were patients aged 18-65 years
      with signs and symptoms consistent with ureteral colic. RESULTS: Among the 40
      patients enrolled in the routine IVP group, 26 had positive studies, 8 of which
      necessitated hospitalization. Among the 41 patients randomized to the selective
      IVP group, there were only 19 IVPs performed, of which 6 were positive and 4
      necessitated hospitalization. Compared with the routine IVP group, there were 54%
      fewer IVPs performed and a 51% lower admission rate in the selective IVP group.
      Despite the fact that fewer IVPs were performed in the selective IVP group,
      clinical outcomes in the 2 groups were similar, without significant complication
      in either group. CONCLUSIONS: IVPs do not need to be routinely performed for all
      patients presenting to the ED with ureteral colic. The decision to perform an IVP
      may be dictated by symptoms that persist after initial evaluation and treatment.

PMID- 9262696
TI  - The significance of out-of-hospital hypotension in blunt trauma patients.
AB  - OBJECTIVE: To determine the significance of a low out-of-hospital systolic blood
      pressure (SBP) reading in blunt trauma patients who have a normal SBP upon ED
      arrival. METHODS: A retrospective case-control study compared admitted blunt
      trauma patients who were hypotensive (SBP < or = 90 mm Hg) in the field and
      normotensive in the ED (group 1) with those who were normotensive both in the
      field and in the ED (group 2). The groups were compared for mortality, intensive
      care unit (ICU) admission, injury severity scale (ISS) score, need for
      transfusion in the ED, incidence of intra-abdominal injury, and incidence of
      pelvic or femur fracture. RESULTS: Each group consisted of 52 patients. The
      groups were similar with respect to age, gender, and initial ED SBP. The group 1
      patients had a higher mortality (10 vs 1, p = 0.008), a higher number of ICU
      admissions (28 vs 12, p = 0.001), more pelvic or femur fractures (16 vs 7, p =
      0.03), and a higher ISS score (19.0 vs 10.5, p = 0.01). Although not significant,
      group 1 also had higher incidences of intra-abdominal injury (10 vs 3, p = 0.07)
      and transfusion (8 vs 2, p = 0.09). CONCLUSION: The injured patients who were
      hypotensive in the out-of-hospital setting but normotensive upon ED arrival were
      more severely injured and had more potential for blood loss than were the
      patients who were normotensive both in the out-of-hospital setting and in the ED.
      Out-of-hospital hypotension may be a clinical predictor of severe injury, even in
      the face of normal ED SBP. Prospective studies are indicated to validate this
      hypothesis.

PMID- 9262697
TI  - Failure of the Miller criteria to predict significant intracranial injury in
      patients with a Glasgow Coma Scale score of 14 after minor head trauma.
AB  - OBJECTIVE: To determine the utility of the Miller criteria (presence of headache,
      nausea, vomiting, and signs of depressed skull fracture) for predicting the need
      for CT in patients with minor head trauma and a Glasgow Coma Scale score (GCS) of
      14. METHODS: The study was a prospective, consecutive series of all patients
      undergoing head CT scans with a GCS of 14 following head trauma. A data sheet was
      completed for all patients prior to obtaining a head CT scan. RESULTS: 264
      patients were entered into the study and 35 patients were found to have traumatic
      abnormalities on head CT scan. The use of the Miller criteria to select those
      patients who would require head CT scan would have resulted in missing 17 of the
      35 abnormal scans, including 2 patients who required neurosurgical intervention.
      These 2 patients were markedly intoxicated upon presentation. CONCLUSION: The use
      of the Miller criteria as the only criteria for screening patients with a GCS of
      14 after minor head trauma who require a head CT scan is not recommended. While
      the authors have identified ethanol intoxication as one confounding factor,
      further refinement of this risk-stratification tool is required.

PMID- 9262698
TI  - The impact of an endotracheal side port on the absorption of lidocaine.
AB  - OBJECTIVE: To compare lidocaine levels after administration through an i.v. line,
      a standard endotracheal (ET) tube, and an ET tube side port (ETSP) designed for
      medication administration. METHODS: A double-blind, prospective, triple crossover
      canine study was performed. Seventeen anesthetized mongrel dogs were given
      standard doses of 2% lidocaine via i.v. (1.5 mg/kg), endotracheally through the
      main lumen (3 mg/kg diluted in 10 mL normal saline), and endotracheally through
      the modified side port (3 mg/ kg diluted in 10 mL normal saline). Arterial blood
      gases (ABGs) and plasma lidocaine levels were measured at time 0, 30 sec, 1 min,
      5 min, 10 min, 20 min, 30 min, and 60 min. Mean lidocaine levels across time,
      comparing the 3 methods of administration, were analyzed with repeated-measures
      analysis of variance. The main outcome was the comparison of mean ET and ETSP
      lidocaine levels at each time point using paired t-tests. The attainment and
      duration of lidocaine levels considered therapeutic in cardiac arrest (1.4
      micrograms/mL) were described. ABGs were measured at each point to describe
      trends in oxygenation. RESULTS: Mean lidocaine levels, comparing the 3 methods of
      administration, were significantly different at all time points except time 0.
      The ETSP levels were significantly lower than the ET main-lumen levels at 30 sec,
      1 min, 5 min, and 10 min. i.v.-administered lidocaine attained quick therapeutic
      levels and revealed faster elimination. Lidocaine administered through the ET
      main lumen reached therapeutic levels more slowly, and maintained such levels
      longer. Lidocaine administered through the ETSP never reached therapeutic levels.
      Mean PO2S remained > 340 torr throughout each method of administration.
      CONCLUSION: This nonarrest canine model suggests that lidocaine levels achieved
      through an ETSP are lower than levels obtained with the same drug dose via an ET
      main lumen. Therapeutic lidocaine levels are obtainable by i.v. or ET main-lumen
      routes, but not via this ETSP.

PMID- 9262699
TI  - Utility of urine and blood cultures in pyelonephritis.
AB  - OBJECTIVE: To determine how often the results of urine and blood cultures led to
      changes in antibiotic therapy for patients discharged from the hospital with the
      diagnosis of pyelonephritis. METHODS: A retrospective chart review was performed
      of consecutively admitted patients, 10-90 years old, with an ICD-9 discharge
      diagnosis of acute pyelonephritis. All patients were admitted to a university
      based, tertiary care center and a large HMO medical center from 1993 to 1994. The
      association of urine and blood culture results with a change in antibiotic
      therapy was assessed. RESULTS: Of the 194 patients who met inclusion criteria,
      189 (97%) had urine cultures obtained at the time of admission and 139 (71%) had
      blood cultures obtained. Ampicillin, gentamicin, or both were given as initial
      antibiotics 81% of the time, and isolated organisms from urine or blood were
      sensitive to the empiric antibiotics 95% of the time. Most (171/189; 90%) urine
      cultures were positive, but only 9 (5%) of these led to a change in antibiotic
      therapy. 80% of the urinary pathogens were Escherichia coli, 5% Enterococcus, 5%
      Proteus, and 4% Klebsiella. Only 40 (29%) of the 139 blood cultures were
      positive; none prompted a change in antibiotics. There were no cases in which
      blood and urine cultures grew different pathogens. CONCLUSIONS: Urine cultures
      are useful in directing antibiotic therapy in patients with the discharge
      diagnosis of acute pyelonephritis and support a change in therapy in 5% of cases.
      Among the patients in this study, blood cultures results did not lead to changes
      in antibiotic therapy. These findings warrant prospective, multicenter
      evaluation.

PMID- 9262700
TI  - Predictive value of letters of recommendation vs questionnaires for emergency
      medicine resident performance.
AB  - OBJECTIVE: To evaluate the predictive value of standard letters of recommendation
      (LORs) vs preprinted questionnaires (PPQs) for resident performance at one
      emergency medicine (EM) residency program. METHODS: A retrospective association
      of LORs and PPQs with in-training residents performance ratings was done at one
      EM residency program. The residency application files of EM residents who
      completed the program were reviewed to locate files that had LORs and PPQs
      written by the same author. Seventeen resident files contained 32 LOR/PPQ pairs.
      These LORs and PPQs were submitted in a blinded fashion to 3 outside EM residency
      directors. Each LOR and PPQ was evaluated for the applicant's suitability for the
      specialty of EM, medical knowledge, procedural skills, interpersonal skills,
      motivation, and overall rank. The scores given by the outside reviewers were
      compared with resident performance ratings determined by 5 EM attending
      physicians who evaluated the residents along the same 6 dimensional ratings.
      RESULTS: Statistically, no differences were found between the LORs and PPQs in
      predicting resident performance. CONCLUSIONS: PPQs may substitute for LORs in the
      evaluation of resident applicants.

PMID- 9262701
TI  - Wound botulism associated with black tar heroin.
AB  - The incidence of wound botulism is increasing and the epidemiology of the disease
      is changing. The majority of new cases are associated with injection drug use, in
      particular, the use of Mexican black tar heroin. This case report and discussion
      of wound botulism illustrate the following important points: Dysphagia,
      dysphonia, diplopia, and descending paralysis, in association with injection drug
      use, should alert the treating physician to the possibility of wound botulism. In
      such patients, the onset of respiratory failure may be sudden and without
      clinically obvious signs of respiratory weakness. For the reported patient,
      maximum inspiratory force measurements were the only reliable indicator of
      respiratory muscle weakness. This is a measurement not routinely performed in the
      ED, but may prove essential for patients with suspected wound botulism. To
      minimize the effect of the botulinum toxin and to decrease length of hospital
      stay, antitoxin administration and surgical wound debridement should be performed
      early.

PMID- 9262702
TI  - Clinical pearls. Stab wound to the left forearm.

PMID- 9262703
TI  - Use of the World Wide Web for multisite data collection.
AB  - As access to the Internet becomes increasingly available, research applications
      in medicine will increase. This paper describes the use of the Internet, and,
      more specifically, the World Wide Web (WWW), as a channel of communication
      between EDs throughout the world and investigators who are interested in
      facilitating the collection of data from multiple sites. Data entered into user
      friendly electronic surveys can be transmitted over the Internet to a database
      located at the site of the study, rendering geographic separation less of a
      barrier to the conduction of multisite studies. The electronic format of the data
      can enable real-time statistical processing while data are stored using existing
      database technologies. In theory, automated processing of variables within such a
      database enables early identification of data trends. Methods of ensuring
      validity, security, and compliance are discussed.

PMID- 9262704
TI  - Statistical methodology: III. Receiver operating characteristic (ROC) curves.
AB  - Measures including sensitivity, specificity, and positive and negative predictive
      values have been traditionally used to assess a diagnostic test's ability to
      detect the presence or absence of disease. Receiver operating characteristic
      (ROC) curve analysis allows visual evaluation of the trade-offs between
      sensitivity and specificity associated with different values of the test result,
      or different "cutpoints" for defining a positive result. The purpose of this
      article is to define, construct, and interpret a ROC curve using a hypothetical
      example applicable to emergency medicine practice.

PMID- 9262705
TI  - Sonographic detection of a renal mass in a young adult: a case for radiologic
      screening of new-onset ureteral colic.

PMID- 9262706
TI  - Letters of recommendation: what does good really mean?

PMID- 9262707
TI  - Bilateral blindness.

PMID- 9262708
TI  - Tension hydrothorax.

PMID- 9262709
TI  - The relative risks.

PMID- 9262710
TI  - Power error.

PMID- 9262711
TI  - Amrinone and verapamil overdose study design.

PMID- 9262712
TI  - Assessment of dehydration in adults using hematologic and biochemical tests.

PMID- 9262713
TI  - Multivisceral surgery in advanced gastric carcinoma.
AB  - From April 1986 to June 1994 a total of 284 patients with gastric carcinoma were
      admitted to the authors' department. Mainly advanced tumour stages were seen:
      stage I = = 23%, II = 13%, III = 22% and IV = 42%. In 256 tumour resections
      (resection rate = 90%) multivisceral surgery (mvs) was necessary in 146 patients
      (mvs = 57%). Long-term survival of stage IV gastric cancer patients cannot be
      prolonged by mvs, and RD-resection can be achieved in few patients (9/120 = 7.5%
      in stage IV). Perioperative morbidity, postoperative complications and the mean
      postoperative hospital stay were increased after extensive surgery. Major
      complications were anastomotic leakage, local infections and pulmonary diseases.
      Even when resection seems to be an acceptable palliation for stage IV gastric
      cancer patients, mvs in only justified where RD-resection seems achievable.

PMID- 9262714
TI  - The role of invasive sonography in the differential diagnosis and treatment of
      intraabdominal fluid collections.
AB  - Sixty-nine ultrasound-guided interventions (23 punctures and 46 drainages) were
      performed on 51 patients with the suspicion of intraabdominal abscess or another
      type of fluid collection in a prospective-controlled study. Of the procedures,
      58.8% were carried out following surgery, while in 41.2% the indication were not
      related to prior surgical intervention. Repeated procedures were done in 10
      patients. In the group of punctures the procedure was therapeutic in 3 cases and
      diagnostic in 16 patients. The drainage was technically successful in 92.7%. The
      drain was displaced or blocked in 27% (n = 10), but reinterventions were
      necessary in only 5 cases for this reason. The total number of redrainages was
      18.9%. The percutaneous (pc) drainage was insufficient in 8 patients (21.6%), all
      these patients were operated on. 62.2% of the patients recovered after pc
      drainage, 13.5% following redrainage (total 75.5%). In 8.1% of the cases after pc
      drainage and in 5.4% after pc redrainage open surgery became necessary. There was
      only one complication due to the procedure. Seven patients (14.3%) died of the
      disease which indicated the procedure. There were no fatal outcomes on the
      account of the intervention. Ultrasound-guided puncture is a suitable method to
      indicate or contraindicate open surgery in the case of intraabdominal fluid
      collection. The diagnostic puncture may be followed by sonographically guided
      drainage or in selected cases by therapeutic puncture, but if the pc drainage is
      insufficient, open surgery should be performed in time.

PMID- 9262715
TI  - Occurrence and significance of Helicobacter pylori infection after gastric
      surgery.
AB  - Occurrence and significance of Helicobacter pylori (Hp) infection in patients
      having undergone partial and total gastric resection was studied. Forty-nine
      patients after gastric resection with Billroth I and II operation (28 patients
      due to ulcer and 21 patients due to gastric cancer), and 8 patients with total
      gastrectomy due to gastric cancer were selected. In addition, 40 patients with
      active peptic ulcer disease, 32 patients suffering from gastric cancer, and 28
      patients with non-ulcer dyspepsia as a control group were enrolled. Occurrence of
      Hp in patients having been operated on due to ulcer disease was slightly lower
      than in controls (50% vs. 54%), but it was significantly lower than in patients
      with active peptic ulcer (50% vs. 85%, p < 0.001). On the other hand, in patients
      who were operated on due to gastric cancer, Hp was much less frequent than in the
      control group, as well as in patients in the preoperative period (9.5% vs. 54%
      and 72%, p < 0.001). As a conclusion, since in our series colonization with Hp
      was found to be less frequent after gastric resection than before surgery, its
      aetiologic significance in postoperative chronic gastritis and ulceration seems
      to be unlikely. Therefore, the routine postoperative eradication of Hp appears to
      be unnecessary in such patients.

PMID- 9262716
TI  - Pseudophakic retinal detachment.
AB  - PURPOSE: Extracapsular cataract extraction and intraocular lens implantation have
      become a widespread surgical method in Hungary during the last 10 years.
      Consecutive pseudophakic retinal detachment cases show an increasing trend.
      METHOD: 27 patients with pseudophakic retinal detachment were observed during a 3
      year period. Careful fundus examination was carried out with indirect
      ophthalmoscopy, slit-lamp biomicroscopy and ultrasonography. The surgical method
      of choice was a standard operation (scleral buckling, encircling bend, cryopexy
      and laser coagulation) as first approach, or, in cases of PVR pars plana
      vitrectomy with fluid-gas exchange or silicon oil implantation. When reoperation
      was required, standard methods and/or pars plana vitrectomy with silicon oil
      implantation was applied. RESULTS: 17 out of 27 retinas reattached. Reoperation
      was necessary in 10 cases. Standard method failed in 8 out of 17 cases.
      Vitrectomy was successful in nine out of 17 cases. CONCLUSION: Pseudophakic
      retinal detachment often produces diagnostic difficulties: smell, undilatable
      pupils, capsular fibrosis, slightly decentred intraocular lens inhibit detection
      of tears. In these cases vitrectomy is recommended as first surgical approach. In
      severe cases removal of the intraocular lenses should be considered.

PMID- 9262717
TI  - Intraoperative pachymetry during excimer photorefractive keratectomy.
AB  - The evaluation of pre- and intraoperative corneal thickness is of great
      importance in photorefractive surgery and in planning phototherapeutic
      treatments. The authors evaluated 14 eyes with Humphrey ultrasonic pachymeter
      Model 855 during photorefractive keratactomies (PTK). All treatments were
      performed with the Aesculap Meditec MEL 60 ArF excimer laser. The preoperative
      uncorrected visual acuity averaged 0.078 +/- 0.068. The average of preoperative
      correction used to obtain the best corrected visual acuity was: -6.11 +/- 3.70.
      The average preoperative corneal thickness was found at 548.14 +/- +/- 24.58
      microns; the average thickness of the mechanically removed epithelium was: 51.5
      +/- 1.49 microns. After PRK the corneal thickness decreased to 440.78 +/- 33.2
      microns. The thickness of the photoablated corneal tissue was on the average
      55.86 microns measured by the ultrasound pachymeter. The pachymeter values
      correlated well with the average of 53.21 +/- 30.19 microns thickness change
      calculated by the excimer laser combi modul display monitor. The authors
      conclude, that ultrasound pachymeter is suitable for evaluating pre- and intra
      operative corneal thickness. Echobiometric pachymetry is valuable in planning and
      executing phototherapeutic treatment. It permits the surgeon to assess
      intraoperatively the thickness of the already ablated corneal tissue and reduce
      the risk of postoperative refractive changes. The method is also suitable for
      controlling the photorefractive calibration of the excimer laser.

PMID- 9262718
TI  - Laparoscopic appendectomy (LA) with a new technique.
AB  - The technique of LA has evolved during the past decade. We describe a
      simplification using a scope with work channel. TECHNIQUE: A 1.2 cm paraumbilical
      trocar enters the CO2(-)-inflated peritoneum. The 1 cm scope with work channel is
      introduced. If the view confirms the diagnosis of appendicitis we place a 1-cm
      trocar in the midline 2 cm above the symphysis pubis. The scope is switched to
      the 1 cm trocar. The appendix is immobilized through the work channel. Through
      the paraumbilical site the appendiceal artery is clipped or coagulated as
      necessary. The stump is closed by Roeder loops or stapler. The specimen is
      removed through the larger site. The wounds are closed with single sutures.
      CONCLUSION: This technique has the advantage of being less invasive on the
      abdominal wall. The sum of the stab wounds is 2.2 cm, requires only one surgeon
      and the assistance of a scrub nurse. If necessary, the operation it can be
      converted to 3- or 4-trocar technique or an open one.

PMID- 9262719
TI  - Posterior avulsion of the optic nerve due to deceleration trauma.
AB  - A patient with complete transection of the optic nerve (posterior avulsion) and
      explosion of the eyeball, due to an attempted suicide is reported. The symptoms,
      mechanism of injury and therapeutic possibilities in complete transection and in
      partial posterior optic nerve avulsions are discussed. Although this case ended
      up with enucleation, the partial avulsions are not without hope. The importance
      of team-work is emphasized in polytraumatic patients.

PMID- 9262720
TI  - Recent management of colo-rectal tumours and precancerous conditions.
AB  - Authors review the early diagnostic means of colo-rectal cancers and precancerous
      conditions. For treating these patients a detailed protocol for examination,
      surgery, surgical technique, and follow-up is recommended. More active surgical
      solutions are stimulated for the surgical management of primary tumours,
      recurrences and metastases as well.

PMID- 9262721
TI  - Thymic cysts. Report of 10 cases.
AB  - Among 984 mediastinal tumours in the authors' series, 10 thymic cysts were found;
      one of the cysts extended to the neck. The literature is reviewed in relation to
      the aetiology, pathogenesis, pathology, diagnostic features, differential
      diagnosis, therapy and prognosis of thymic cysts.

PMID- 9262722
TI  - Perforated duodenal diverticulum.
AB  - Duodenal diverticula are found in up to 20% of the population but only few
      patients require surgery for acute complications. Perforation is the rarest of
      the complications, just over 100 cases have been reported in the world
      literature. Besides a case report, the characteristics and the therapy of
      duodenal diverticula are reviewed in this report.

PMID- 9262723
TI  - Strangulated intestinal obstruction due to forgotten eroding laparotomy pad.
AB  - Small-bowel obstruction from impacted intraluminal foreign body after laparotomy
      is encountered but rarely. This report presents a case in which a laparotomy pad
      left in the abdomen caused strangulated intestinal obstruction after
      cholecystectomy.

PMID- 9262724
TI  - The effects of variously performed vagotomies on gastric secretion and gastric
      emptying in rats.
AB  - The main purpose of this study was to investigate the effects of (i) truncal
      vagotomy + pyloroplasty, (ii) proximal cell vagotomy and (iii) anterior proximal
      cell vagotomy + posterior truncal vagotomy on the gastric secretion and gastric
      emptying in rats. After vagotomy basal and 2-deoxy-glucose stimulated gastric
      secretion decreased significantly in all three vagotomy groups. Gastric secretion
      on the other hand was significantly higher in the proximal cell vagotomy group
      than on the other vagotomy groups. The rate of gastric emptying in proximal cell
      vagotomy and anterior proximal cell vagotomy + posterior truncal vagotomy groups
      was delayed. The best results were found in the truncal vagotomy + pyloroplasty
      group when the gastric secretion and the rats of gastric emptying are concerned.

PMID- 9262725
TI  - The use of Voltaren (diclofenac sodium, Ciba) in acute renal colic.
AB  - Thirty-one patients with acute renal colic were treated with Voltaren (Diclofenac
      Sodium, Ciba). The drug proved to be suitable for relieving, and stopping pain.
      Adverse effects were observed but in few cases. For this reason authors suggest a
      more extensive use of the drug.

PMID- 9262726
TI  - Comparison of prosthetic materials used for abdominal wall defects or hernias (an
      experimental study).
AB  - The prosthetic materials polypropylene and polytetrafluoroethylene were
      comparatively studied for postinterventional infection, development of adhesions,
      and recurrence of hernias and tissue reactions in rats in which abdominal defects
      1 by 2 cm in size had been repaired with one of these materials. As regards
      infection and hernias there was no significant difference vs. a control group of
      rats. There was no collagen deposition in polytetrafluoroethylene, and the
      mononuclear inflammatory cell reaction and fibroblastic activity outside the
      graft layer were steadily less intense with polytetrafluoroethylene than with
      polypropylene. Adhesions were significantly (p < 0.05) more marked with
      polypropylene.

PMID- 9262727
TI  - Long-term results of minimally invasive lumbar disc surgery.
AB  - Long-term results of minimally invasive primary lumbar discectomies are
      processed. The operation was fairly simple and inexpensive, with reduced hospital
      stay (24 hours). The subsequent rehabilitation was compared to the more extensive
      procedures. The Oswestry-style questionnaires were found to be gratifying with a
      high percentage (80.9%) of patients, who returned to normal or nearly normal
      lives. No significant difference was found with published results of
      microdiscectomy.

PMID- 9262728
TI  - Excimer laser in the treatment of recurrent pterygia.
AB  - Authors report two cases of multiple recurrent pterygia which were treated with
      the usual surgical technique (sec. Arlt) and a subsequent excimer laser
      treatment. In case one they used slit mode, in the other case spot mode was
      applied. The superficial phototherapeutic ablations were performed with an
      Aesculap Meditec MEL 60 193-nm Arf excimer laser. During a one year follow-up
      period recurrence was experienced in both cases. According to the literature in
      primary pterygia the excimer laser might be helpful in the reepithelization by
      smoothing the corneoscleral surface. In recurrent cases, however, the
      glycosaminoglycane content of the collagen fibres are lower in the corneal scar
      tissue, so due to the impaired hydratation, the fluency of the excimer laser
      might fail to ablate the pathological surface structures. On the other hand, in
      recurrent cases the corneoscleral barrier function is also heavily impaired, so
      the conjunctival epithelial cells are not able anymore to recognize the
      corneoscleral border. It is concluded that in recurrent cases the excimer laser
      phototherapeutic treatment is of less value than in primary pterygia.

PMID- 9262729
TI  - Retinoscopy after excimer laser photorefractive treatments.
AB  - Photorefractive keratectomy (PRK) is capable of changing the refractive power of
      the human cornea. Retinoscopy is an objective method of measuring the refractive
      power of the eye. The authors performed PRK in 28 myopic eyes with the Aesculap
      Meditec MEL 60 ArF excimer laser. During a prospective study, the subjective and
      objective refractive power of the eyes were assessed and compared 6 months after
      PRK. The average preoperative refractive error was: -5.11 +/- 2.51 D and -5.08 +/
      2.20 D on the right side (n = 16) and on the left side (n = 12), respectively.
      In order to obtain the best corrected visual acuity 6 months after PRK, the right
      and left eyes needed an average of -0.09 +/- 0.26 D and -0.33 +/- 0.64 D
      postoperative correction, respectively. The postoperative refractive change could
      be verified with the retinoscopy at +/-0.5 D accuracy. The authors describe a
      double refractive corneal ring after PRK, which may disturb retinoscopy. The post
      PRK refractive change can be verified by retinoscopy. Postoperative funduscopy,
      fundus photography and possible future retinal procedures were not disturbed by
      the double corneal refractive rings in myopic eyes.

PMID- 9262730
TI  - Refractive results after photorefractive excimer laser treatment in mild myopic
      and in mild hyperopic eyes.
AB  - Evaluation of 12-month results of photorefractive keratectomies (PRK) performed
      in low myopic (0 to -6.0 D) and low hyperopic (0 to +6.0 D) eyes. Myopic and
      hyperopic PRK treatments with the Aesculap Meditec MEL 60 ArF excimer laser.
      Prospective study, 30 eyes per group. The change in best corrected visual acuity
      (VA), refraction required, uncorrected VA and the postoperative haze were
      compared at the 12th postoperative month. The average preoperative correction in
      the low myopic eyes (Group I) was -4.65 +/- 1.24 D, which decreased to -0.17 +/-
      0.56 D during the follow-up. In mild hyperopic eyes (Group II) the preoperative
      refraction was +3.9 +/- 0.93 D and decreased to +1.23 +/- 1.59 D post-PRK.
      Comparing the pre- and postoperative average best corrected VA values, there was
      no statistical change in either group. In the low myopic group all eyes had a
      20/40 or better uncorrected VA, in hyperopic eyes 11 had a VA of 20/40 or better,
      four had a worse uncorrected VA. In Group I, 86.6% of the eyes were within +/-1.0
      D of the intended refraction at 12 months postoperatively. In Group II, 46.7% of
      the eyes were within +/-1.0 D of final refraction. There were no intergroup
      differences in subjective complaints, reepithelization and average postoperative
      haze. Both methods are able to alter the refractive power of the cornea toward
      emmetropia. The predictability of the method was to be found higher in cases of
      mild myopia than in mild hyperopia. The upper limit of myopia is above -6.0 D,
      but in hyperopia, with the present technical facilities, good postoperative
      results can be obtained only as far as +4.25 D of preoperative refractive error.

PMID- 9262731
TI  - Changes of the corneal endothelium after ultraviolet-B exposure in previously
      photokeratectomized eyes.
AB  - The photorefractive effect of excimer lasers is based on an interaction between
      the 193-nm ultraviolet-C laser beam and the stromal chromophore molecules.
      Recently, in some patients an increase of subepithelial haze and a regression of
      refractive effect has been observed following suntanning (UV-B exposure). The aim
      of the study was to find out the possible endothelial damage caused by
      photoablation with increasing depth and the effect of subsequent UV-B exposure on
      previously photokeratactomized eyes. Altogether 12 chinchilla rabbits were
      treated. Four animals received a -5.0 D PRK; four animals a -15.0 D PRK and four
      animals a -30.0 D PRK treatment. The endothelial average number, size and
      variation were determined two weeks post-PRK. Three weeks following PRK, a half
      of the animals received a 1 J/cm2 ultraviolet-B radiation in a constant
      dermatological UV-chamber. The endothelial morphology was measured the same way
      with automated specular microscopy two weeks after UV-B irradiation. After PRK
      treatment there was no statistically demonstrable change in endothelial
      morphology. On the other hand, after UV-B radiation all eyes showed a decrease in
      endothelial number and an increase in size and variation. The ratio of
      hexagonality decreased, and endothelial rosette formation appeared. The early
      morphological changes resembled the physiological aging changes. Conditions (deep
      stromal photoablation, cumulative effect of suntanning or solarium treatments)
      may exaggerate the physiological aging processes leading to subsequent
      pleomorphism, polymegatism and cell loss. This may accelerate corneal
      dysfunction.

PMID- 9262732
TI  - Experiences with photorefractive excimer laser treatment in compound myopic
      astigmatism.
AB  - The invention of excimer lasers and different masks in order to treat refractive
      failures has opened a new era in refractive surgery. The refractive grading, the
      ablation effect, which can be controlled within one micrometer, and the design of
      a special mask made possible so-called "corneal sculpting" in compound
      astigmatism. The authors evaluated their experiences on 27 myopic compound
      astigmatic eyes. The average age of the patients was 28.67 +/- 9.78 years and the
      average preoperative uncorrected visual acuity was 0.06 +/- 0.04. The spherical
      component averaged -6.74 +/- 2.81 D and the cylindrical component averaged -2.3
      +/- 1.54 D (the preoperative correction needed to obtain the best corrected
      visual acuity). Postoperatively, the uncorrected visual acuity improved to 0.65
      +/- 0.26. To obtain the best corrected postoperative visual acuity an average 
      0.51 +/- 1.06 D sph and an average -0.54 +/- 1.06 D cyl component was needed. The
      authors conclude that ArF excimer laser treatment is able to alter both of the
      spherical and cylindrical components of the eye toward emmetropia. The lower the
      degree of preoperative compound myopic astigmatism, the better are the chances of
      postoperative emmetropia. No serious complications were met during the follow-up
      period.

PMID- 9262733
TI  - Ormond's disease.
AB  - Three cases of Ormond's disease (syndrome) are described, and the
      aetiopathogenesis, clinical picture and diagnostics of the disease are dealt with
      in this report. Besides, the traditional therapy and the new therapeutic
      possibilities are discussed. For a disease of low incidence and assumed
      autoimmune origin malignancy cannot be excluded. Therefore, surgical exploration
      and histological verification are indispensable interventions in every case of
      Ormond's disease. In two of the present cases, steroid was administered in
      defence of percutaneous nephrostomy. In two cases, the recently recommended anti
      oestrogen therapy was successful. Stagnation, or even regression, of the process
      followed. The authors are sure that they were the first in Hungary to administer
      anti-oestrogen to patients suffering from IFR.

PMID- 9262735
TI  - Co-incidence of angioleiomyolipoma and renal cyst.
AB  - Authors report on a 60-years-old female patient with right renal angiomyolipoma
      and solitary cyst. Partial resection of the tumour and the cyst was performed
      during open surgery. Ultrasonography and computerized tomography are mandatory
      methods of the preoperative investigation. The authors give a review of the
      related literature.

PMID- 9262734
TI  - A modified mediocolic approach to removal of local relapse of renal tumour.
AB  - A modified approach is recommended for removal of local relapse following
      leftside nephrectomy. In the course of transperitoneal mesocolic approach, the
      retroperitoneum is opened as usual at Treitz's ligament, between the aorta and
      the inferior mesenteric vein. For further exposure, two or three radial vessels
      are preserved. Thus, sufficient room ir available between these bridges to remove
      the tumour, expose the v. cava and the aorta and remove the renal vessels.
      Mobilization of the colon is not necessary.

PMID- 9262736
TI  - Minimal and direct access ureterolithotomy.
AB  - Authors developed an alternative method to laparoscopic surgery for
      ureterolithotomy. The surgery is of minimal access because the length of the
      single skin incision ranges from 3 to 4 cm, depending on the type of exploration.
      It is of direct access because the surgeon sees the operative area directly and
      stereoscopically with his own two eyes without video-optical support. The
      procedure requires a special open-lumen retractorscope (Jakoscope) with a high
      intensity fiberoptic light system and modified standard hand instruments.
      Ureterolithotomy is operated retroperitoneally through a minilumbotomy incision.
      The procedures are simple, rapid and the instruments are inexpensive. The
      postoperative pain and morbidity are comparable to the laparoscopic approach.

PMID- 9262737
TI  - Federal panel backs early, aggressive HIV therapy.

PMID- 9262738
TI  - New pneumococcal-vaccine recommendations include strategies for increasing
      vaccine use.

PMID- 9262739
TI  - NIOSH recommends steps for reducing work-related exposure to latex.

PMID- 9262741
TI  - Adverse reactions to alternative medicine.

PMID- 9262740
TI  - Prioritizing pharmacy services in the emergency department.

PMID- 9262742
TI  - Restructuring the academic health center for the twenty-first century.

PMID- 9262744
TI  - Peer review and continuous quality improvement of pharmacists' clinical
      interventions.
AB  - A peer-review-based continuous quality improvement (CQI) program for improving
      pharmacists' clinical interventions at a hospital is described. With the
      implementation of pharmaceutical care at Detroit Receiving Hospital came the need
      for a CQI system to validate and improve this type of patient care. A peer-review
      group (PRG) was formed. The PRG decided to review 60 pharmacist interventions per
      month for clinical appropriateness, accuracy of entry into the computer,
      documentation in the medical record by the pharmacist, and implementation if
      accepted by the physician. Interventions are assigned to individual reviewers,
      and final decisions on the appropriateness and correctness of the selected
      interventions are made at periodic PRG meetings. In its first year the PRG met
      nine times and evaluated 409 interventions; 96% of the interventions were judged
      clinically appropriate, 62% were accurately entered into the computer, 62% were
      documented in the medical record by the pharmacist, and 92% were implemented if
      accepted by the physician. Meetings, additional reviews, and inservice sessions
      were used to address deficiencies in the interventions; these efforts led to
      improvements. The clinical appropriateness of documented interventions was
      included as a medication use indicator in the hospital CQI program. A peer-review
      based CQI process allowed a hospital to effectively monitor and improve the
      quality and documentation of interventions recommended by pharmacists.

PMID- 9262743
TI  - Clinical and economic impact of replacing divalproex sodium with valproic acid.
AB  - The impact of replacing divalproex sodium with valproic acid on patient outcomes
      and direct drug costs was studied. Before-and-after medical chart review was
      performed in a state-supported facility for mentally retarded adults in which a
      pharmacy and therapeutics (P&T) committee recommended replacement of divalproex
      with valproic acid. Patients were studied if they had received divalproex for at
      least three months and if their antiepileptic drug was changed from divalproex to
      valproic acid between October 1993 and June 1994. Clinical, economic, and
      prescribing-pattern data were recorded for the periods extending 12 months before
      and 18 months after the change in therapy. Data for 46 patients were analyzed.
      Replacing divalproex with valproic acid was effective in 41 (89%) of the
      patients. There was no significant difference between the divalproex and valproic
      acid periods in seizure rate or frequency of new drug therapy for GI disorders.
      Between fiscal year 1992-93 and fiscal year 1995-96 there was a 56% decrease in
      total direct divalproex plus valproic acid costs, including drug products and
      packaging materials and labor. The rate of valproic acid prescriptions increased
      steadily after the replacement was recommended, and then plateaued. Replacing
      divalproex sodium with valproic acid in a group of institutionalized mentally
      retarded adults with epilepsy was clinically effective and economically
      advantageous.

PMID- 9262745
TI  - Computerized documentation of activities of Pharm.D. clerkship students.
AB  - A method for documenting the contributions of entry-level Pharm.D. clerkship
      students at a teaching hospital is described. Between mid-September 1995 and
      April 1996, students were asked to use a cost-accounting software program to
      document time spent on various activities associated with inpatient pharmacy
      services. The system was already being used for documenting the clinical
      activities of staff pharmacists; pharmacists entered activities in the same way
      that they entered medication orders, using a mnemonic for a clinical activity in
      place of a drug name and time spent on the activity in place of a dosage.
      Pharmacist preceptors verified the students' entries. Eleven students reported
      3,466 clinical events. Thirty-five pharmacists reported 54,299 clinical events
      during the same period. Students were responsible for 42.5% of the initial
      patient work-ups reported, 34.0% of the patient information and education
      episodes, and 24.6% of the inservice programs for physicians. On the basis of
      documented student contributions to the clinical workload, the pharmacy
      department requested additional clerkship students. The following year, 16
      clerkship students were assigned to the department and the program was expanded
      to year-round clerkships. Pharmacy clerkship students contributed to the
      productivity data of a teaching hospital. Documentation of the students'
      contributions led to an expansion of the clerkship program.

PMID- 9262746
TI  - Comparison of information obtained from a Usenet newsgroup and from drug
      information centers.
AB  - Responses to drug information questions posted on the Internet Usenet pharmacy
      newsgroup sci.med. pharmacy were compared for accuracy with responses from drug
      information centers (DICs). Twenty-five questions were randomly selected from the
      past five years' continuing-education sections of the Annals of Pharmacotherapy,
      and possible answers were determined on the basis of corresponding articles. The
      questions were randomly submitted to sci.med.pharmacy from various e-mail
      accounts over a 10-week period. The same questions were submitted by telephone to
      randomly selected DICs. The correctness of responses was judged by a panel of
      four pharmacists. The questions received 31 responses from sci.med. pharmacy and
      38 from the DICs. The responses from sci.med.pharmacy received 38 (31%) judgments
      of correct and the responses from the DICs, 85 (56%). A significantly smaller
      proportion of drug information responses from the Usenet newsgroup
      sci.med.pharmacy were judged as being accurate compared with responses from DICs.

PMID- 9262747
TI  - Compatibility of cisatracurium besylate with selected drugs during simulated Y
      site administration.
AB  - The compatibility of cisatracurium besylate with 91 other drugs during simulated
      Y-site injection was studied. Five milliliters of cisatracurium 0.1, 2, and 5
      mg/mL (as besylate) in 5% dextrose injection was combined with 5 mL of each of 91
      drugs in 5% dextrose injection or 0.9% sodium chloride injection. All
      combinations were prepared in duplicate and stored at approximately 23 degrees C.
      Samples were visually examined under normal laboratory fluorescent light and, if
      there was no obvious visual incompatibility, under high-intensity monodirectional
      light. Turbidity was measured as well. Particle sizing and counting was performed
      for selected combinations. All evaluations were performed at intervals up to four
      hours. Cisatracurium besylate at all three concentrations was compatible with
      most of the drugs tested. However, one drug (cefoperazone) was incompatible with
      cisatracurium besylate at all three concentrations, 14 (including many
      cephalosporins) were incompatible with cisatracurium besylate 2 and 5 mg/ mL, and
      12 were incompatible with cisatracurium 5 mg/ mL. During simulated Y-site
      administration, cisatracurium 0.1, 2, and 5 mg/mL (as besylate) in 5% dextrose
      injection was compatible with 64 of 91 drugs for four hours at approximately 23
      degrees C. Twenty-seven drugs were incompatible with cisatracurium besylate at
      one or more concentrations.

PMID- 9262748
TI  - Financial impact of clinical research on a health system.

PMID- 9262749
TI  - Regulating managed care in an integrated health system environment.

PMID- 9262750
TI  - Appropriateness of maximum-dose guidelines for vincristine.

PMID- 9262751
TI  - Giving partial doses of transdermal patches.

PMID- 9262752
TI  - Pharmacist as newspaper columnist.

PMID- 9262753
TI  - Implementation of a computerized drug information database.

PMID- 9262755
TI  - Night landings on an aircraft carrier: hospital mergers and antitrust law.

PMID- 9262756
TI  - The conversion conundrum: the state and federal response to hospitals' changes in
      charitable status.

PMID- 9262757
TI  - ERISA preemption and regulation of managed health care: the case for managed
      federalism.

PMID- 9262758
TI  - Resource allocation in the National Health Service.

PMID- 9262759
TI  - The U.S. health delivery system: inefficient and unfair to children.

PMID- 9262761
TI  - Ensuring the safety of genotech drugs through implied warranty theory.

PMID- 9262760
TI  - The due process right to a safe and humane environment for patients in state
      custody: the voluntary/involuntary distinction.

PMID- 9262762
TI  - Mechanisms of burn injury secondary to airbag deployment.
AB  - The efficacy of airbags as a vital, supplemental restraining device has been
      proven by their role in diminishing the rate of fatalities and severity of injury
      in motor vehicle crashes. Unfortunately, as with any developing technology,
      deployment of the airbag itself has caused some new problems. Most airbag-related
      injuries are minor and, surprisingly, more than 5% are burns typically involving
      the upper extremity or head and neck. These are a result of the high temperature
      of the gases released during inflation or of direct contact with the corrosive
      alkaline plume created as a combustion by-product. Fortunately, these are
      superficial burns that usually require only expectant treatment, but a high
      degree of suspicion in these circumstances is needed to make the proper
      diagnosis.

PMID- 9262763
TI  - Spontaneous autoinflation of saline mammary implants.
AB  - This study was prompted by 5 patients (seen by OGR) presenting with unilateral
      enlargement of the breasts 4 to 9 years following augmentation mammaplasty with
      saline-filled implants. At exploration one breast implant was seen to be markedly
      enlarged when compared to the other, with a brownish yellow material that had the
      consistency of serum. Studies were undertaken to determine the permeability of
      the silicone container to various body fluids and a study of the contained fluid
      itself. Protein measurements, viscosity measurements, and osmotic water
      permeability measurements were performed. The results were consistent with the
      hypothesis that these silicone implants were indeed permeable to both water,
      glucose, and protein. We hypothesize that the mechanism underlying this in vivo
      expansion is colloid osmotic swelling. Why one breast should be more involved
      than the other is unknown. We believe that this phenomenon is occurring more
      frequently than is being reported.

PMID- 9262764
TI  - Poland's deformity reconstructions with a customized, extrasoft silicone
      prosthesis.
AB  - Chest and breast reconstruction with a customized prosthesis in 5 patients with
      Poland's syndrome are presented. The customized, textured silicone prostheses are
      fabricated from an extrasoft silicone polymer that more closely approximates the
      softness of natural tissue. Two women and three men underwent the reconstructive
      procedure. Both women had composite implants made of the solid, extrasoft polymer
      in the superior portion and silicone gel with a saline fill option for the breast
      portion. The men were reconstructed with solid, textured prostheses that filled
      the various chest deficiencies and irregularities of their Poland's deformity.
      Seroma formation was seen in 2 patients and needle aspirations were required to
      resolve the problem. All patients have comfortable, soft, and aesthetically
      acceptable results after a mean of 5 years. The reconstructive technique
      presented with this initial group of patients is a simple, alternative procedure
      to the more complex surgery of muscle transposition. The extrasoft polymer is an
      advance in implant technology that merits consideration for use in a customized
      prosthesis when reconstructing patients with Poland's syndrome deformity.

PMID- 9262766
TI  - End-on-side microvascular anastomosis: an experimental study.
AB  - A new method, the end-on-side microanastomotic technique, is presented and also
      compared with the conventional end-to-side technique. The technique can be
      summarized as follows: The proximal end of the donor vessel is incised
      bilaterally at midlateral points. Thus it is separated into inferior and superior
      segments. These segments are placed to overlap the posterior and anterior walls
      of the recipient artery by using two vertical sutures. Two additional horizontal
      sutures are placed between the apexes of the midlateral incisions and the apexes
      of the arteriotomy on the recipient artery. Eventually the microanastomosis is
      totally completed with four sutures lying at the intramural position in the
      recipient artery. Twenty rabbits were equally divided into two groups. The
      femoral and the profunda femoris arteries were used bilaterally to investigate
      applicability of the end-on-side technique in the first 10 rabbits. Eighteen end
      on-side anastomoses were observed to be patent in the first stage. Subsequently
      the end-on-side technique was compared with the conventional end-to-side
      technique in the other 10 rabbits. All anastomoses, both end on side and end to
      side, were patient. Four end-on-side microanastomoses were histologically
      evaluated. It was proved that the end-on-side technique is a feasible and
      experimentally reliable method.

PMID- 9262765
TI  - Evaluation of penicillin and hyperbaric oxygen in the treatment of streptococcal
      myositis.
AB  - The purpose of this study was to evaluate effects of hyperbaric oxygen (HBO) and
      penicillin (PCN) therapy in a murine model of streptococcal myositis. The thighs
      of Swiss Webster mice were inoculated with Streptococcus pyogenes. Four groups
      were evaluated: (1) control (N = 10), (2) HBO treatment (N = 10), (3) PCN
      treatment (N = 8), and (4) PCN and HBO treatment (N = 6). Mortality (day of
      death) and the number of colony-forming units (cfu) were measured. PCN
      significantly lowered cfu from control (p < 0.05). Cfu in group 4 was
      significantly lower than PCN alone (p = 0.006). Survival was significantly longer
      in the PCN group compared with the control (p < 0.01). Survival in the combined
      treatment group was significantly longer than PCN alone (p < 0.01). These results
      suggest that (1) HBO treatment alone does not decrease mortality or bacterial
      proliferation in vivo significantly, (2) PCN therapy alone improves outcome
      significantly, and (3) the combined treatment of PCN and HBO exerts at least
      additive effects in both decreasing bacterial counts in vivo and increasing
      survival in this model.

PMID- 9262767
TI  - Adjuvant therapy: the effects on microvascular lower extremity reconstruction.
AB  - Adjuvant therapy and microsurgery have allowed advances in surgical extirpation
      of lower extremity neoplasms. This retrospective study was designed to evaluate
      the microvascular transfer for lower extremity reconstruction in patients
      receiving pre- or post-operative irradiation and chemotherapy alone and in
      combination. Over a 5-year period, 24 free tissue transfers were performed in 22
      patients undergoing surgical resection with adjuvant therapy for lower extremity
      neoplasms. There were 13 male and 9 female patients with an average age of 51
      years. The latissimus dorsi muscle was most commonly transferred (N = 15).
      Eighteen tumors received pre- and three received postoperative radiotherapy. Two
      tumors received a combination of radiotherapy and brachytherapy. Pre- and/or
      postoperative chemotherapy was used in 14 patients. Twelve of these patients had
      both chemo- and radiation therapy. A total of six complications occurred, with no
      flap loss. Complications were evenly distributed among adjuvant regimens. All
      patients who underwent attempted limb salvage were able to ambulate
      postoperatively, except for 1 patients who had local recurrence. In conclusion,
      adjuvant therapy did not increase the complication rate for free tissue transfer
      in the lower extremity. Adjuvant therapy did not require alterations in the free
      tissue transfer and, similarly, free tissue transfer did not alter adjuvant
      therapy. We believe that free tissue transfer in complicated wounds allows for
      better wound healing with adjuvant therapy rather than local or primary wound
      closure alone.

PMID- 9262768
TI  - Clinical applications of the delayed arterialized venous flap.
AB  - Arterialized venous flaps have been used clinically but still have limited
      applications for coverage of small surface defects. Varying degrees of necrosis
      of the larger, arterialized venous flaps remain an unsolved problem. We have
      treated 13 patients, with acute soft-tissue defects in 9 patients and scar
      contracture in 4 patients, with surgically or surgically-chemically delayed
      arterialized venous flaps from 1993 to 1995. There were 9 males and 4 females.
      The average age of the 13 patients was 34.7 years. Donor sites were the medial
      calf in 4 patients, the volar surface of the forearm in 6 patients, the dorsum of
      the foot in 2 patients, and the medial thigh in 1 patient. Before
      arterialization, surgical delay was done in 9 patients and a combined surgical
      chemical delay in 4 patients. There were 12 skin flaps and one composite
      tendocutaneous flap. The follow-up period ranged from 5 to 28 months, with an
      average of 15 months. The surviving surface area of the arterialized venous flap
      was 100% in 10 patients, axial 70% in 1 patient, axial 50% in 1 patient, and
      total necrosis in the remaining patient. Among the 10 flaps with total survival,
      the minimal flap size was 6 x 8 cm and the maximal flap size was 14 x 16 cm.
      Advantages of the delayed arterialized venous flap are (1) developing a larger
      flap than can be obtained with a pure venous flap or arterialized venous flap and
      (2) the increased survival rate of the arterialized venous flap, which permits
      the possibility of using a composite flap. This delayed arterialized venous flap
      also has all the advantages of the pure venous flap, such as preservation of the
      main artery of the donor site; thin, nonbulky tissue; and easy elevation without
      deep dissection. The disadvantage is the requirement of a two-stage operation.

PMID- 9262769
TI  - Bone morphogenetic protein promotes vascularization and osteoinduction in
      preformed hydroxyapatite in the rabbit.
AB  - Early reconstruction of large osseous defects in children is often delayed due to
      limited availability of autogenous bone graft donor sites. With the advent of
      growth factors, osteoinductive proteins, and delivery matrices, it is possible to
      fabricate new bone at extraskeletal sites. Due to their own blood supply,
      adequate bony volume, and decreased resorption, vascularized bone flaps have
      demonstrated greater success in restoring large bony defects compared with
      nonvascularized bone grafts. The purpose of this study is to prefabricate a
      vascularized bone flap in the immature-age rabbit using the auricularis anterior
      muscle as a muscle pedicle. Sixteen female New Zealand White rabbits, 2.0 to 2.5
      kg, were divided into two groups. Group 1 contained 8 animals that had T-shaped,
      10 x 6 x 4-mm hydroxyapatite (HA) implants combined with 100-microgram bovine
      derived bone morphogenetic protein (BMP) placed supraperiosteally and fixed deep
      to the auricularis anterior muscle. Implants with HA alone were placed in the
      same animal and secured to the contralateral auricularis anterior muscle. Group 2
      contained 8 animals that had HA/BMP placed subperiosteally and fixed deep to the
      auricularis anterior muscle, while implants with HA alone were secured in the
      same animal to the contralateral auricularis anterior muscle. In each group, 4
      animals were sacrificed at 4 and 8 weeks. The animals underwent randomized
      bilateral carotid artery injection with micropaque barium suspension just prior
      to sacrifice to help maintain vascularity. At harvest the implants and
      surrounding muscle and cranium were removed en bloc. New bone formation in the HA
      implants was examined by using routine histology and scanning electron
      microscopic backscattering image (quantitative) analysis. Microradiographs were
      performed on representative specimens. At 4 weeks postimplantation,
      backscattering analysis in the subperiosteal HA/BMP showed a mean 17.1% bone
      ingrowth vs. 11.3% of HA alone (p < 0.05). Supraperiosteal HA/BMP showed a mean
      12.9% bone ingrowth vs. 0% of HA alone (p < 0.05). At 8 weeks, backscatter
      analysis of supraperiosteal HA/BMP showed a mean 19.33% bone ingrowth vs. 0% of
      HA alone (p < 0.05). Subperiosteal HA/BMP showed a mean 22% bone ingrowth vs.
      20.85% of HA alone. This was the only group that did not have statistically
      significant results. Implant histology demonstrated woven bone within the
      interstices of HA/BMP placed either supra- or subperiosteally. In the HA-alone
      implants placed supraperiosteally, fibrovascular ingrowth was seen without any
      evidence of bone formation. In the HA-alone implant placed subperiosteally, woven
      bone was seen at the calvarium-implant junction. Microradiographs also
      demonstrated vascularization and bone formation similar to that seen on scanning
      electron microscopy. BMP-treated specimens appeared to have slightly greater
      vascularity than the nontreated specimens. The greatest bone formation occurred
      with the HA/BMP implant placed subperiosteally in the immature rabbit.
      Furthermore, these results demonstrate the potential prefabrication of
      vascularized bone flaps as early as 4 to 8 weeks. The clinical advantage of HA
      permits the surgeon to design osseous flaps that are customized in shape, fill
      all contour defects, and have little resorptive properties. Such prefabricated
      bone with an axial blood supply may allow for ultimate transfer as a pedicle or
      free flap to reconstruct osseous defects in children.

PMID- 9262770
TI  - Effective treatment of hypertrichosis with pulsed light: a report of two cases.
AB  - Hypertrichosis is an often stigmatizing cosmetic problem not only for women but
      also for male-to-female transsexual patients. The hitherto described therapeutic
      measures include chemical epilation, razoring, camouflage, electrolysis and
      thermolysis, and waxing. All of these measures are transient, more or less
      painful, and may lead to severe side effects (e.g., inflammatory responses and
      scarring). We report the successful treatment of the perioral and mandibular area
      of two transsexual patients (male to female), who we treated with a recently
      introduced intense, pulsed light source--the PhotoDerm VL. Two days after the
      nearly painless treatment, hair could be epilated easily with forceps. Biopsies
      of the treated area show an atrophy of the follicles, which can be contributed
      either to direct thermal injury or to an indirect photothermolytical effect. Six
      months after the last treatment, there is no local recurrence and no side
      effects.

PMID- 9262771
TI  - Treatment of a degloved hand injury by arteriovenous anastomosis: a case report.
AB  - It goes without saying that the optimal therapy for reconstruction of degloving
      injuries is to employ the tissues that were avulsed. However, it is difficult to
      evaluate the circulation and viability of avulsed tissues, and in the case of
      conservative treatment it is quite common for the avulsed tissues to become
      necrotic. This often necessitates a second reconstructive operation. We report a
      case of degloving injury of the hand. We performed reconstruction by
      arteriovenous anastomosis of a superficial vein in the avulsed skin flap and a
      superficial vein of the hand with the radial artery. We were thereby able to
      arterialize and salvage the avulsed skin flap on the back and palm of the hand,
      and the results were cosmetically and functionally satisfactory.

PMID- 9262772
TI  - A method of breast reconstruction with a deepithelialized TRAM flap via the
      abdominal approach for failed implant salvage in postmastectomy patients.
AB  - Postmastectomy reconstruction of breasts is one of the most commonly performed
      procedures of the plastic surgeon today. Tissue expansion with subsequent implant
      placement, transverse rectus abdominis musculocutaneous (TRAM) flaps, latissimus
      dorsi flaps, gluteal flaps, Ruben's fat pad flaps, and free flaps from other
      areas have all been utilized with consistently good aesthetic results. One
      special class of patient is the woman who has undergone breast reconstruction
      with tissue expansion, with or without subsequent implant placement, who than
      receives external beam radiation therapy. Capsular contraction frequently
      complicates this therapy. In the past, women have undergone capsulotomy or
      capsulectomy with replacement of the implant. Recently, women are more reluctant
      to have foreign tissue in their bodies and are opting for autologous tissue
      reconstructions. TRAM reconstruction following removal of implants has been
      previously reported. A new approach to the placement of the TRAM flap after
      implant reconstruction via the abdominal approach, with avoidance of any incision
      on the breast itself, is presented. This is especially important in a patient who
      has evidence of radiation damage to the skin, placing any incision through the
      treated tissue at risk.

PMID- 9262773
TI  - Functional reconstruction of total lower lip defects with a radial forearm free
      flap combined with a depressor anguli oris muscle transfer.
AB  - Two total lower lip reconstructions were accomplished by combining a radial
      forearm free flap and a depressor anguli oris muscle transfer. The radial forearm
      flap was used to reconstruct the inner surface of the lower lip. The bipedicled
      musculofascial flap, which includes both depressor anguli oris muscles, the
      depressor labii inferioris muscles, and the mentalis muscles, was elevated onto
      the chin and sutured superiorly to the modioli to obtain innervated sphincter
      function. Good results were obtained both aesthetically and functionally.
      Electromyography revealed almost normal mobility of the depressor anguli oris
      muscles 6 months after the operation. No drooling was seen during mastication,
      and no air leakage was observed during puffing of the cheeks. This is an
      effective procedure for the reconstruction of the sphincter function of the lower
      lip.

PMID- 9262774
TI  - Calvarial deformity and remodeling following prolonged scalp expansion in a
      child.
AB  - A main concern in the use of scalp tissue expansion in the pediatric population
      has been the risk of skull deformation. Little is known about the long-term
      effects of tissue expansion on the skull and the ability of the skull to remodel
      following removal of the tissue expander. We report a recent case in which a 5
      year-old boy had a fully inflated tissue expander retained under the scalp for a
      15-month period. At surgery for removal of the implant the patient was noted to
      have a profound skull deformity characterized by severe calvarial depression and
      ridging. The patient underwent scalp reconstruction. Follow-up at 6 months
      revealed nearly complete remodeling of the skull with minimal visual deformity.
      This case demonstrates not only the profound bony deformity that can result from
      tissue expansion, but also the striking ability of the pediatric skull to
      remodel.

PMID- 9262775
TI  - A combined reverse temporalis muscle flap and pericranial flap for reconstruction
      of an anterior cranial base defect: a case report.
AB  - After the excision of a recurrent squamous cell carcinoma in a 52-year-old man, a
      reverse temporalis muscle flap combined with a pericranial flap was used to
      reconstruct the anterior cranial base and the frontal defect. The combined flap
      is based on the superficial temporal fascia supplied by the superficial temporal
      vessels. We recommend the usage of the combined reverse temporalis muscle flap
      and the pericranial flap for reconstruction of the anterior cranial base, the
      frontal region, and other facial defects.

PMID- 9262776
TI  - The great saphenous vein fasciocutaneous island flap for immediate calcaneal
      wound reconstruction.
AB  - Reconstruction of a calcaneal wound in an obese elderly diabetic was accomplished
      with a Type I venous fasciocutaneous flap based on the great saphenous vein. This
      unique reconstruction has several advantages including ease of dissection and
      preservation of arterial inflow into the distal foot.

PMID- 9262777
TI  - The reverse lateral arm adipofascial flap for elbow coverage.
AB  - The reverse lateral arm adipofascial flap covered immediately with a skin graft
      has been used successfully for reconstruction of a cubital fossa defect (caused
      by avulsion injury) and an exposed olecranon (resulting from recurrent bursitis)
      in 2 patients. The flap is nourished by the septal perforators of the posterior
      radial collateral artery, which in turn obtains its blood supply from the
      interosseous recurrent artery. The distal vascular pedicle should contain a
      sufficient amount of subcutaneous fat and its underlying fascia to enhance the
      arterial input and the venous drainage of the flap. The primary benefit of this
      technique is that the thickness of the flap can be tailored to fit into the
      defect, and the donor site can be closed primarily without tension. The
      advantages include satisfactory cosmetic results, a rapid one-stage procedure, no
      sacrifice of the main artery or local muscle, and avoidance of any long-term
      immobilization of the involved elbow joint.

PMID- 9262778
TI  - Brachioradialis musculocutaneous flap closure of the elbow utilizing a distal
      skin island: a case report.
AB  - A brachioradialis musculocutaneous flap with a distal skin island is described to
      close a chronic elbow wound. This newly described distal skin island directly
      over the brachioradialis tendon provides viable and durable coverage for the
      olecranon/posterior elbow region. The advantages and disadvantages of this
      treatment as compared with other historical reconstructive options for this
      region are analyzed. The patient has a stable healed wound at 2 years of follow
      up.

PMID- 9262779
TI  - Bilobed fasciocutaneous flap for primary repair of a large upper arm defect with
      secondary closure of the donor site without a skin graft.
AB  - Primary repair of 2 patients with large upper arm defects with the bilobed
      fasciocutaneous flap is reported. In this procedure the repair of a large soft
      tissue defect with a flap prepared adjacent to the defect and closure of the flap
      donor site are performed at the same time without a skin graft. This procedure
      enabled regional reconstruction and provided excellent aesthetic results. It is
      simple and reliable. In addition, primary repair of large upper arm defects can
      be expected.

PMID- 9262780
TI  - A unilateral cleft lip patient with holoprosencephaly.
AB  - Holoprosencephaly includes a spectrum of conditions that have in common the
      associated anomalies of false median cleft lip, nasal malformation, orbital
      hypotelorism, and brain malformations. We recently encountered a patient with
      holoprosencephaly presenting with a rare unilateral cleft of the lip. This
      patient was potentially viable, although mental development was retarded.

PMID- 9262781
TI  - Uncommon Klinefelter's variant (49,XXXXY) with cleft palate.
AB  - The karyotype 49,XXXXY is a rare form of Klinefelter's syndrome. Various
      anomalies can be found in this variant--more than other variants of Klinefelter's
      syndrome. Cleft palate is rarely seen among these anomalies. A cleft palate
      deformity can be diagnosed early and easily. This deformity should cause one to
      suspect an uncommon variant of Klinefelter's syndrome. Here we present a patient
      with an uncommon variant of Klinefelter's syndrome who was diagnosed with the
      help of the presence of an incomplete cleft palate deformity.

PMID- 9262782
TI  - A clever solution.

PMID- 9262783
TI  - Z-plasty practice for the beginner.

PMID- 9262784
TI  - Hemangioma of the nasal bones.

PMID- 9262785
TI  - Parenting the prematurely born child.
AB  - The purpose of this chapter is to summarize the findings of the nursing research
      on parenting the prematurely born child. This research focused on eight general
      areas: impact of the home environment on infant development status, the
      relationship between premature infants and their mothers during the first 2
      years, parenting during hospitalization, maternal concerns about infant
      discharge, fathering, subpopulations of premature infants, parenting after the
      first 2 years, and interventions to improve parenting. There is a need to
      strengthen the design and conceptualization of these studies, to move toward more
      intervention research, and to do research that is more culturally sensitive,
      especially toward fathers, ethnic and cultural minority groups, and the poor.

PMID- 9262786
TI  - Interventions for cognitive impairment and neurobehavioral disturbances of older
      adults.
AB  - This synthesis of the research literature includes a discussion of selected
      neurobehavioral disturbances that accompany impairments in cognitive functioning
      in older adults. A combination of computerized and manual searches was used to
      access interdisciplinary and nursing research reports on the care and treatment
      of older adults who are cognitively impaired. The results demonstrated that
      protocols are needed that systematically integrate and evaluate extant working
      knowledge and evolving research bases for proactive preventive approaches to the
      care of cognitively impaired older adults with neurobehavioral disturbances.

PMID- 9262787
TI  - Uncertainty in acute illness.
AB  - In this chapter, the research on uncertainty in acute illness is reviewed and
      critiqued. Both qualitative and quantitative studies are included. The review
      considers the cause and consequences of uncertainty from research on adults and
      from research on parents of acutely ill children.

PMID- 9262788
TI  - Violence in the workplace.
AB  - This integrative review of research on workplace violence in Canada and the
      United States showed that risk factors for homicide and nonfatal assault injuries
      differed significantly. In 1993, there were 1,063 work-related homicides in the
      United States (Bureau of Labor Statistics, 1994). Workplace homicide was the
      second leading cause of fatal occupational injuries overall, but the primary
      cause for women. The highest risk for workplace homicide was observed among
      males, the self-employed, and those employed in grocery stores, eating and
      drinking establishments, gas service stations, taxicab services, and government
      service, including law enforcement. The majority of workplace homicides occurred
      during robberies. Unlike workplace homicide, the majority of nonfatal assaults
      that involved lost work time occurred to women, primarily employed in health care
      or other service sector work. The assault rates for residential care and nursing
      and personal care workers were more than ten times that of private non-health
      care industries. Minimal intervention research has been reported. In recent
      years, some governmental agencies and professional organizations have begun to
      address policy issues related to workplace violence.

PMID- 9262789
TI  - Interventions to reduce the impact of chronic disease: community-based arthritis
      patient education.
AB  - Systematic development and testing of the efficacy of educational interventions
      to improve functioning, prevent disability, and reduce the impact of chronic
      disease has been limited, perhaps because many chronic diseases disable, do not
      kill, and because they are managed largely within home, work, and community
      environments and not within the medical care system. Until recently, these
      factors contributed to a paucity of arthritis educational interventions. But
      since the impetus provided by the establishment of the Multipurpose Arthritis
      Centers Program of the NIH (1977), a number of arthritis patient education
      programs have been established and evaluated. This chapter summarizes findings
      from community-based arthritis patient education studies conducted between 1980
      and 1995, critiques the methods of these studies, and provides guidance for state
      of-the-art community-based intervention research aimed at reducing the individual
      and social impact of arthritis and other chronic diseases.

PMID- 9262790
TI  - Parent-adolescent communication in nondistressed families.
AB  - The focus of this chapter is parent and adolescent communication in nondistressed
      families. Communication is the assertive and unoffensive expression and accurate
      and attentive receipt of opinions, feelings, and ideas. Aspects of adolescent and
      adult development have been shown to influence as well as be influenced by
      perceptions of family communication. Though recently subject to extensive
      scrutiny and criticism, the paradigm of parent and adolescent conflict dominates
      this research area. Nurses and other have demonstrated strategies to enhance
      communication between parent and adolescents, with promising results. Issues of
      subject participation are reviewed and recommendations for future directions in
      research and practice are made.

PMID- 9262792
TI  - Health promotion and disease prevention in the worksite.
AB  - U.S. and Canadian research studies (n = 73) on health promotion/disease
      prevention programs in the worksite reported from 1990 through 1994 were reviewed
      for this chapter. In those studies, diverse intervention foci were provided and
      outcomes specific to the foci, as well as numerous additional outcomes, cost and
      cost benefit being the most common, were measured. To aid future researchers, two
      appendices list reports by foci of intervention and by outcomes measured.
      Deficiencies and inadequacies in reports and studies are described. Nearly all
      (68 out of 73) of the published studies obtained positive results in terms of
      benefiting health or reducing costs. The Johnson & Johnson LIVE FOR LIFE Program
      is presented as an exemplar of a comprehensive, multifaceted, worksite health
      promotion/disease prevention program whose effects were consistently assessed.
      Although health promotion and prevention of disease has always been an important
      component of nursing practice, few reports included nurse scientists as authors
      or coauthors. Potential explanations for the limited involvement by nurse
      scientists and recommendations regarding future research directions are
      presented. The worksite remains the best place to promote improved health for
      adults and this area of research represents an opportunity for greater
      involvement by nurse scientists.

PMID- 9262791
TI  - Adherence to therapy in tuberculosis.
AB  - Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide. In the
      United States, TB has undergone a resurgence and the appearance of multidrug
      resistant TB has caused new concerns. A critical part of TB treatment is
      adherence to the prescribed therapy for a considerable time period. Treatment
      "failure" is often due to nonadherence. Many factors influence adherence to
      therapy in TB. This chapter reviews research in the area of adherence to the TB
      treatment plan in the United States and worldwide. It discusses adherence as an
      outcome related to treatment regimens such as directly observed therapy, patient
      characteristics, life and family circumstances, motivation, education,
      incentives, and combination strategies. Themes across studies are compared and
      suggestions for successful future studies are identified.

PMID- 9262793
TI  - Nursing at war: catalyst for change.
AB  - From the first development of nursing research agendas, scholars have called for
      historical inquiries into nursing's heritage and the influences that have
      affected the development of the profession. Because war leaves an indelible and
      distinct mark on the era in which it occurs, periods of significant development
      and change in nursing's heritage can be linked to involvement in war. This review
      explores the published scholarship about American nurses in wartime, from the War
      for Independence through the Persian Gulf War and notes the most significant
      changes that have come as a result of this involvement. Although particular wars
      and wartime nursing is a popular topic for historical inquiry, there are still
      eras that need to be further explored for contributions to the profession of
      nursing as it is today.

PMID- 9262794
TI  - Long-term vascular access devices.
AB  - Introduced in the 1970s, long-term vascular access devices are used in both
      adults and children, with about 500,000 devices placed annually. This integrative
      review of research on dressings to minimize infectious catheter-related
      complications showed that current practices were adapted from knowledge derived
      from short-term central venous and peripheral catheters without thorough
      investigation. Summary and critique of recent, as well as older significant
      studies, provide guidance for future research. Specifically, future research
      should demonstrate greater confidence in outcome measures with attention to
      reliability of laboratory methods, diagnostic criteria, and interrater
      reliability. Continuing research efforts are needed to capture unique design
      features of various devices, qualify device performance across prolonged time,
      examine nuances within patient subgroups, and address underrepresented patients
      and settings. Confounding and interacting variables require greater attention in
      study design and analysis.

PMID- 9262795
TI  - Nursing research in Taiwan.
AB  - Nursing research in Taiwan has evolved over the past 30 years. This review
      focused on refereed publications, research published in English, and specifically
      the 27 studies produced by doctorally prepared first authors. Most investigators
      used surveys and interviews. Designs were at the levels of description,
      association, and evaluation, not at the level of experiment. Problems are
      identified for this body of research. Further evolution of nursing science in
      Taiwan needs to incorporate the scientific and technologic resources of the world
      to develop nursing knowledge.

PMID- 9262796
TI  - Time to bite the [abuse] bullet.

PMID- 9262797
TI  - Child abusers, the abused, and the murdered: in our nation and your state.
AB  - In an effort to alert pediatric dental practitioners to the ongoing epidemic of
      child victimizations and murder, a review provided of Department of Justice and
      Department of Health and Human Services reports, including data on the
      perpetrators of these crimes and a state by state review of these criminal
      events.

PMID- 9262798
TI  - A comparison of plaque removal effectiveness of an electric versus a manual
      toothbrush in children.
AB  - The purpose of this study was to test the plaque-removing efficacy of an electric
      brush (Philips HP550) in comparison with a manual brush (Butler Gum 111) in five-
      to ten-year-old uninstructed children. The sample included twenty-three children
      who were divided into two groups, each group brushing for four weeks with the
      assigned brush at home. After this period children were asked to brush for two
      minutes in a dental clinic. Plaque was scored according to the Turesky modified
      Quigley and Hein Index before and after brushing. Analysis shows that plaque
      reduction with the electric brush is significantly better than with the manual
      brush: 46 percent versus 25 percent reduction, respectively. Results are most
      marked for the lingual posterior areas. Results further indicate that using an
      electric brush, plaque is reduced more evenly over the dentition. Participants
      without previous experience with powered toothbrushes showed no problem in
      adapting to the electric brush.

PMID- 9262799
TI  - Initial tensile bond strength of resin-modified glass ionomers and polyacid
      modified resins on perfused primary dentin.
AB  - The objective of this study was to evaluate the initial tensile bond strength of
      a resin-modified glass ionomer (Photac-Fil) and two polyacid-modified composite
      resins (Compoglass, Dyract) to primary dentin. A hybrid composite resin (Tetric)
      and two chemical cured glass ionomers (BaseLine, Hi-Dense) served as controls.
      Ninety caries-free dentinal discs were ground flat and perfused with Ringer's
      solution. Dentinal surfaces were conditioned (except for Base Line). From each
      material, fifteen standardized specimens were attached to the dentin. Light
      curing of the respective materials followed (1 min), and adhesion was tested with
      a universal testing machine 15 min after application. The highest initial bond
      strength was observed with Tetric (5.17 MPa). Closed test procedure (Kruskal
      Wallis) showed significant differences between all materials (P < 0.05), except
      for Compoglass (1.82 MPa) vs. Dyract (2.35 MPa), and BaseLine (0.37 MPa) vs.
      Photac-Fil (0.42 MPa). The condensable glass ionomer Hi-Dense revealed a mean
      tensile bond strength of 0.79 MPa. Adhesion of (polyacid-modified) composite
      resins is superior to the other tested glass ionomer materials, when applied to
      perfused primary dentin.

PMID- 9262800
TI  - Alveolar bone height of primary and first permanent molars in healthy seven- to
      nine-year-old children.
AB  - The purpose of the study was to establish baseline values of the alveolar bone
      height of the primary molars and first permanent molars in sample of healthy U.S.
      seven- to nine-year-old children. Direct measurements of the distance from the
      cementoenamel junction (CEJ) to the alveolar crest (AC) on 223 pairs of bitewing
      radiographs from 223 subjects were made using a digimatic caliper under
      standardized conditions. The distance from the CEJ to the AC had medians from
      0.58 mm to 1.39 mm (range 0.0 to 4.44 mm) for the primary molars and from 0.00 mm
      to 0.64 mm (range -1.35 to 2.15 mm) for the mesial aspect of the permanent
      molars. There were no statistically significant differences in the distance from
      CEJ to AC between teeth on the right and left sides of the mouth. The distances
      from CEJ to AC were always greater in the maxilla than in the mandible for
      similar primary molar sites, but only true for the mesial aspect of the permanent
      first molar at age nine. As a tooth is positioned more anteriorly in the mouth,
      the distance from CEJ to AC was greater. On the whole, males had greater
      distances than females and eight-year-olds had larger distances than seven- or
      nine-year-olds. Differences were observed in the measured distances for the
      different age and sex-groups and may be attributable to variations in eruption
      and exfoliation patterns. The distance was significantly greater in areas of
      interproximal restorations and open contacts, and there was a tendency for the
      distances to be greater in areas of interproximal caries.

PMID- 9262801
TI  - A comparative study of midazolam to meperidine/promethazine as an IM sedative
      technique for the pediatric dental patient.
AB  - This study evaluated the efficacy and safety of midazolam (0.2 mg/kg) as an IM
      sedative agent in the pediatric population as compared to the standard IM
      meperidine (2.0 mg/kg)/promethazine (1.0 mg/kg) sedation technique. Ten pediatric
      dental patients, ASA Class I, were evaluated in this double-blind, randomized,
      crossover study. The patients ranged in age from two to four years. Vital signs,
      sedation levels, and anxiety levels were evaluated. Midazolam was shown to be
      safe, but the inferior drug compared to the standard IM meperidine/promethazine
      sedation technique.

PMID- 9262802
TI  - Mutans streptococcal serotypes in children with gastroesophageal reflux disease.
AB  - It has been suggested that vomiting acid gastric contents in bulimia might favor
      oral growth of Streptococcus sobrinus. We studied the colonization of
      Streptococcus sobrinus (serotypes g and d) and Streptococcus mutans (serotypes c,
      e and f) in sixteen children, ages five to fifteen years, who had suffered for
      four to eleven years from gastroesophageal reflux, another condition with
      recurrent acid regurgitation. Our aim was to find out if the prevalence of
      Streptococcus sobrinus would be higher also in this patient group. Mutants
      streptococci were detected in twelve out of sixteen (75 percent) study patients
      of the saliva samples cultured on MSB agar. For the Mutans streptococci positive
      children healthy controls were matched by salivary levels of mutans streptococci
      and age as closely as possible. From each child three to six isolates
      representing both Streptococcus mutans and Streptococcus sobrinus (n = 103) were
      serotyped by immunodiffusion method. The distribution of serotypes in the
      study/control group was: c: 7/10; e: 4/2; f: 0/1; g:3/2; d:0/0. One strain in the
      study group remained untypable. All patients infected with Streptococcus sobrinus
      were also infected with Streptococcus mutans. Our results indicate the great
      similarity in the distribution of ms serotypes in the gastroesophageal reflux
      children and their healthy controls. The data do not suggest that the acid
      regurgitation would have an influence on the prevalence of Streptococcus
      sobrinus.

PMID- 9262804
TI  - Clinical outcomes for nursing caries treated using general anesthesia.
AB  - This study did follow-up examinations of 84 Medicaid-eligible children with
      nursing caries after they received treatment for nursing caries utilizing general
      anesthesia. Results at six months suggest that parents are unresponsive to follow
      up care and over half of the children seen had new smooth surface caries lesions.
      While results are preliminary, they suggest that major changes are needed in the
      tertiary care of children with nursing caries.

PMID- 9262803
TI  - Oral self-injurious behavior in the developmentally disabled: review and a case.
AB  - Self-injurious behavior occurs in conjunction with a variety of psychiatric
      disorders as well as various developmental disabilities and some syndromes. The
      behavioral and biochemical aspects of self-injurious behavior are poorly
      understood and several etiologies have been suggested. Treatments for self
      injurious behavior in developmentally disabled individuals fall into three main
      categories: pharmacological, behavior modification and physical restraints. The
      dental management of self-injurious behavior is often difficult. Numerous
      appliances of various design have been reported in the literature. Osteotomies or
      extraction of the offending teeth may have to be considered if less invasive
      methods are unsuccessful. A case is reported where a child engaged in tonic lip
      biting secondary to a neurological and seizure disorder is treated using a
      removable lip-protruding device. No impression or lab construction is required.
      The appliance presents minimal interference with oral hygiene procedures and it
      can be removed and reinserted as needed. We conclude that a removable lip-bumper
      may be a viable option in treating transient and acute episodes of self-injurious
      behavior involving the lower lip and buccal mucosa.

PMID- 9262805
TI  - Changes in families and getting youngsters to the dentist.
AB  - Bureau of the Census surveys for the mid-1990s, with projections into the early
      years of the next century, indicate a continuing increase in the numbers of
      single-parent families, grandparent supervised children, families with two
      employed parents and a wide variety of child care arrangements. Pediatric
      dentists increasingly will need to deal with juggled parental work schedules,
      unavailability of parents/guardians and any number of difficulties resulting from
      changed family structures in both traditional and nontraditional patient
      populations.

PMID- 9262806
TI  - CHARGE syndrome: review of literature and report of case. Coloboma, heart
      disease, atresia of choanae, retarded mental development, genital hypoplasia, ear
      abnormalities-deafness.
AB  - Because of the medical characteristics of this inheritable disorder, the
      treatment of these patients can be fraught with potential pitfalls. Oral
      manifestations can include taurodontism of the pulp chambers, retrognathia,
      palatal constriction with attendant posterior crossbite, frontal tongue
      posturing, and mouth breathing relating to airway restriction from choanal
      atresia. The authors describe their treatment of a patient three years of age
      with a tracheostomy.

PMID- 9262807
TI  - Preservation of permanent teeth in a patient with Papillon-Lefevre syndrome by
      professional tooth-cleaning.

PMID- 9262808
TI  - Two-crew operations: stress and fatigue during long-haul night flights.
AB  - BACKGROUND: As part of a research program concerning legal aspects of two-pilot
      operations on long-haul routes, the purpose of the study was to investigate two
      crew extended range operations during a flight roster with two consecutive night
      flights and a short layover. HYPOTHESIS: Present flight time regulations may not
      be adequate for two-crew minimum operations. METHODS: The study was conducted in
      cooperation with a German airline company on the route Frankfurt (FRA)-Mahe
      (SEZ). There were 11 rotations (22 flights) that were investigated by pre-, in-
      and post-flight data collection each time from the two pilots. Recordings
      included sleep, taskload, fatigue and stress by measurement of EEG, ECG, motor
      activity, and subjective ratings. The average actual flight times were 9:15 h
      (FRA-SEZ) and 9:53 h (SEZ-FRA). All flights took place at night. The layover
      duration in Mahe was 13:30 h during day-time. RESULTS: During layover, sleep was
      shortened by 2 h on average compared with 8-h baseline sleep. The two consecutive
      night duties resulted in a sleep loss of 9.3 h upon return to home base. Inflight
      ratings of taskload showed moderate grades, but for fatigue ratings an increasing
      level was observed. Fatigue was more pronounced during the return flight and
      several pilots scored their fatigue at a critical level. Motor activity,
      brainwave activity (occurrences of micro-events) and heart rate indicated
      drowsiness and a low state of vigilance and alertness during both night flights,
      but these effects were more pronounced during the second flight. CONCLUSIONS:
      From the findings it is concluded that a duty roster, as conducted in this study,
      may impose excessive demands on mental and physiological capacity.

PMID- 9262810
TI  - Relationship between age and susceptibility to altitude decompression sickness.
AB  - BACKGROUND: Susceptibility to altitude decompression sickness (DCS) is influenced
      by a multitude of factors including, potentially, an individual's age. Previous
      attempts by authors to determine the effect of age on DCS susceptibility have
      produced conflicting results. The purpose of this study was to try to clarify
      that conflict and to quantify the impact of age on DCS risk. METHODS: We examined
      the Armstrong Laboratory DCS Hypobaric Research Database containing data on 1299
      subject flight exposures conducted from 1983-94. Subjects were from 18-45 yr of
      age. Exposure altitudes ranged from 11,500 ft (3505 m) to 30,000 ft (9144 m). The
      duration of exposure varied from 3-8 h and preoxygenation time ranged from 0-2 h
      and 15 min. Data were compiled according to seven age groups. RESULTS: The
      results show a significant three-fold increase in susceptibility between the age
      group 18-21 and the group > 42 yr of age. The results also show a trend toward
      increased susceptibility between the 18-21 group and the groups between 26 and 41
      yr of age. However, there was no significant change within the range of 26-41 yr.
      CONCLUSION: There is a trend toward increased DCS susceptibility with increasing
      age, with a particularly strong trend for individuals over 42 yr of age.

PMID- 9262809
TI  - Acutely shifting the sleep-wake cycle: nighttime sleepiness after diurnal
      administration of temazepam or placebo.
AB  - HYPOTHESIS: Sleepiness on the job is a common problem suffered by people involved
      in night shift work, especially in conditions of abrupt reversal of the sleep
      wake cycle, such as emergencies and combat air operations. It is well known that
      sleepiness can severely affect alertness and performance. One of the most useful
      countermeasures is to take a prophylactic nap before working at irregular hours.
      To induce and maintain sleep in the "forbidden zones for sleep" during the day,
      it is possible to use suitable benzodiazepine hypnotics such as temazepam (TMZ).
      However, it is then necessary to monitor sleepiness and performance the night
      following the diurnal intake of the drug in order to evaluate possible side
      effects. METHODS: In this study, sleepiness was subjectively and objectively
      measured during the night after a daytime administration of TMZ 20 mg in soft
      gelatine capsules or placebo to obtain a prophylactic sleep. RESULTS AND
      DISCUSSION: Results showed the effectiveness of TMZ for inducing and maintaining
      diurnal sleep. This lengthening of total sleep time did not cause a decrease of
      sleepiness during the night, but no significant carry over effect of TMZ was
      present for nighttime sleep tendency. Both polygraphic and subjective measures of
      sleep latency decreased during the night. Finally, no significant relationship
      between the Stanford Sleepiness Scale and the Multiple Sleep Latency Test
      measures was found.

PMID- 9262811
TI  - Effects of altitude hypoxia on middle latency auditory evoked potentials in
      humans.
AB  - BACKGROUND: This paper presents an investigation of auditory evoked responses in
      humans subjected to high altitude hypoxic conditions. METHODS: Middle latency
      (MLAEPs) as well as short latency (BAEPs) evoked potentials were recorded in 10
      healthy subjects, first at sea level (N), then 24 h (H1) and 72 h (H3) after
      their arrival at an altitude of 4350 m. At the same time, arterial blood
      parameters (PaO2, PaCO2 and pH) were measured and the clinical status of the
      subjects was assessed. RESULTS: In altitude conditions, the amplitude of BAEP
      peak V decreased (-17%). The MLAEP waves showed variations in the shape of their
      latest waveforms. Their amplitudes, however, were not affected. The Pa-Nb
      interpeak latency significantly decreased (-2.2 ms) between N and H1, and
      remained stable during the stay at high altitude. CONCLUSION: A correlation was
      found between the relative decrease of PaCO2 and the shortening of Nb wave
      latency, suggesting that the variations in MLAEPs could be preferentially related
      to the ventilatory response of the subjects in hypoxic conditions. However, no
      correlation was found between the clinical status of the subjects (Acute Mountain
      Sickness score) and the parameters of the waves.

PMID- 9262812
TI  - Renal function of substance P in rats chronically exposed to hypoxia.
AB  - BACKGROUND: We studied the renal action of substance P (SP) in rats chronically
      exposed to hypoxia (high altitude, HA), compared to control rats kept at sea
      level (SL). METHODS: Hypoxia was induced by placing female Wistar rats (182-225
      g) in an altitude chamber (5500 m) 15 h.d-1 for 4 weeks. RESULTS: Intrarenal
      arterial infusion of substance P (60 ng.kg-1. h-1) increased the excretion of
      urine, sodium in both groups of rats, however, the excretion of kallikrein (KK)
      and the glomerular filtration rate (GFR) were not significantly altered. After
      aprotinin (10,000 kiu.kg-1. min-1) treatment, kallikrein was depleted, and
      substance P lost its diuretic action. Spantide, an SP antagonist (6000 ng.kg-1. h
      1, I.V.) decreased urine, and urinary excretion of sodium and potassium in SL
      rats, but not in HA rats. Acute renal denervated diuresis in SL rats was not
      modified after Spantide administration. Finally, it was found that both SP and SP
      antagonist did not significantly change the renal parameters in either group of
      rats after chronic renal denervation. CONCLUSION: We made the following
      conclusions: a) endogenous renal action of SP was suggested in SL but not in HA
      rats; b) the renal action of SP might be through KK release, although urinary KK
      did not increase after SP administration; and c) SP action is renal nerve
      dependent in both groups of rats.

PMID- 9262813
TI  - Relationship of leg strength and power to ground reaction forces in both
      experienced and novice jump trained personnel.
AB  - METHODS: There were 14 male soldiers who participated in this study examining the
      relationship of leg strength and power on landing performance. Subjects were
      separated into two groups. The first group (E, n = 7) were parachute training
      instructors and highly experienced in parachute jumping. The second group of
      subjects (N, n = 7) had no prior parachute training experience and were
      considered novice jumpers. All subjects were tested for one-repetition maximum (1
      RM) squat strength and maximal jump power. Ground reaction forces (GRF) and the
      time to peak force (TPF) at landing were measured from jumps at four different
      heights (95 cm, 120 cm, 145 cm, and 170 cm). All jumps were performed from a
      customized jump platform onto a force plate. RESULTS: No differences were seen
      between E and N in either IRM squat strength or in MJP. In addition, no
      differences were seen between the groups for time to peak force at any jump
      height. However, significantly greater GRF were observed in E compared to N.
      Moderate to high correlations between maximal jump power and GRF (r values
      ranging from 0.62-0.93) were observed in E. Although maximal jump power and the
      TPF was significantly correlated (r = -0.89) at only 120 cm for E, it was
      interesting to note that the correlations between MJP and the time to peak force
      in E were all negative and that the correlations between these variables in N
      were all positive. CONCLUSIONS: These results suggest that experienced
      parachutists may use a different landing strategy than novice jumpers. This
      difference may be reflected by differences in GRF generated during impact and a
      more efficient utilization of muscle power during the impact phase of the
      landing.

PMID- 9262814
TI  - Arm arterial occlusion cuffs as a means of alleviating high +Gz-associated arm
      pain.
AB  - In an aircraft used under sustained high +Gz conditions, if the stick and
      throttle are positioned such that the pilot's hands are 20 cm or more below heart
      level, the consequent rise in forearm venous pressure (FVP) may give rise to arm
      pain, which is exacerbated by positive pressure breathing for G protection (PBG).
      This study examined the use of arm arterial occlusion cuffs (AAOC) as a means of
      pain alleviation. Six subjects were exposed on a human centrifuge to a simple
      acceleration profile of +7 Gz for 15 s, (onset rate 1 G.s-1), and to a complex
      profile of +4.8 Gz for 10 s followed by +7 Gz for 10 s, repeated 3 times.
      Subjects wore full coverage anti-G trousers, used PBG (+2 Gz out-in and 10 mm
      Hg/G), and performed runs with and without inflation of AAOC, during which
      invasive measurement of FVP was made. During the simple acceleration profile
      without AAOC, FVP rose to a mean peak of 209 mm Hg and arm pain was severe. With
      inflation of the AAOC, FVP rise was curtailed at a mean peak of 158 mm Hg and
      pain was absent. However, during sequential +7 Gz plateaus of the complex
      profile, AAOC inflation was associated with serially increasing FVP, which was
      significantly higher than that without AAOC inflation (p < 0.05 and p < 0.001 for
      second and third plateaus, respectively), giving rise to immediate and severe arm
      pain. Therefore, the use of arm arterial occlusion as a means of alleviating arm
      pain is unsuccessful.

PMID- 9262815
TI  - Mathematical model for the calculation of oxygen concentrations in a closed
      circuit oxygen rebreathing apparatus.
AB  - BACKGROUND: Closed circuit oxygen rebreathing diving apparatus are used by armed
      forces in special tasks because of their advantages of long endurance, low noise
      and minimal gas escape. There is little knowledge about the administered oxygen
      concentrations in these systems. Closed circuit oxygen rebreathing apparatus are
      also used as a first aid device for the treatment of severe disorders. Because of
      similar constructive components, these rebreathing apparatus are comparable to
      the Drager LAR V model. HYPOTHESIS: This study was conducted to measure the
      oxygen concentrations in the LAR V and estimate the correlation between oxygen
      concentration and pre-breathing purges. METHOD: Subjects were 12 males who
      performed the pre-breathing procedure. The oxygen concentrations in the breathing
      loop were measured after each purge. RESULTS: The oxygen concentrations depended
      on the volume of the apparatus dead space, the total capacity of the divers
      breathing system respective to the volume of the breathing purges and the number
      of pre-breathing purges. The maximum oxygen concentration was reached after eight
      purges (O2 = 85%). An equation to estimate the oxygen concentration inside the
      LAR V and first aid rebreather was derived. CONCLUSIONS: The results indicated
      that the present purging procedure (three purges) before diving is normally not
      sufficient to remove the nitrogen totally from the deadspace of the LAR V, the
      divers airways and lungs. Only a small modification (six purges) is necessary to
      improve the safety of the diver in case of a diving apparatus malfunction during
      the mission profile.

PMID- 9262816
TI  - Changes in radioactive tracer distribution in rats after 24 hours of 45 degrees
      hind limb unweighting.
AB  - INTRODUCTION: Changes in radioactive tracer distribution were examined in rats
      after exposure to a simulated microgravity model of 45 degrees head down tilt
      (45HDT) or 45 degrees hind limb unweighting (45HU) for up to 24 h. METHODS: Rats
      were randomly assigned to either 45HDT (or 45HU) experimental groups or control
      groups for each time point of 0.5 h, 1 h, 2 h, 4 h, 8 h, or 24 h. The 0.5-h
      through 8-h experimental rats were anesthetized and placed head-down on a ramp at
      45 degrees, while control rats were placed in a prone position. Non-anesthetized
      rats in the 24-h experimental group were tail-suspended at 45 degrees, while
      control rats were allowed unrestrained movement. Technetium-labeled
      diethylenetriamine pentaacetate (99mTcDTPA, physical half-life of 6.02 h, MW =
      492 amu) and indium-labeled diethylenetriamine pentaacetate (111In DTPA, physical
      half-life of 3.5 d, MW = 545 amu) were used to measure body organ distributions
      of the radioactive tracers at the 0.5-h-8-h and 24-h time points, respectively.
      Major organs were harvested after each time period and measured for radioactive
      counts. Light and electron micrographs were examined. RESULTS: Mean 111InDTPA
      counts for the lungs, kidneys, and brains of the 24 h 45HU groups were
      significantly higher than control counts. Light and electron microscopy
      demonstrated the development of pulmonary edema in the alveolar septal areas
      after 2 h of 45HDT, and a shift in edema to the pulmonary airways and pulmonary
      arteries after 24 h of 45HU. CONCLUSIONS: Pulmonary edema development,
      accompanied by a significant increase in 111InDTPA lung, kidney, and brain counts
      in the 24-h 45HU groups, suggests vascular injury in the microcirculation of
      these organs.

PMID- 9262817
TI  - Head positioning for high +Gz loads: an analysis of the techniques used by F/A-18
      pilots.
AB  - A study was undertaken among Royal Australian Air Force fighter pilots to
      determine whether, as an occupational group, they had developed any particular
      protective head positioning strategies in order to minimize their risk of
      sustaining a +Gz-induced neck injury during air combat maneuvering. There were 42
      F/A-18 Hornet pilots who responded to an anonymous questionnaire which asked
      about head positioning strategies. Of these, 29 pilots reported using a
      protective strategy. Several pilots reported using several different techniques.
      The most popular strategy reported was positioning the head prior to the
      application of +Gz (13 respondents). Eleven pilots reported using aircraft
      structures to wedge or brace their heads against. The results of this study show
      that fighter pilots who are regularly exposed to high +Gz forces develop an
      individualized approach to protecting their cervical spines from +Gz-induced
      injury.

PMID- 9262818
TI  - The Dynamic Aviation Data System (DADS).
AB  - This paper proposes The Dynamic Aviation Data System (DADS), which integrates a
      variety of existing information sources regarding flight to serve as a tool to
      pilots in dealing with the challenges of flight. The system is composed of three
      main parts: a pilot's history on disk; a system that can read proposed flight
      plans and make suggestions based upon Geographical Information Systems, weather,
      aircraft, and case report databases that exist throughout North America; and a
      small hand-held computer that interfaces with the aircraft's instruments and that
      can be brought into the cockpit to aid the pilot before and during flight. The
      system is based upon technology that currently exists and information that is
      already regularly collected. While many issues regarding implementation and cost
      efficiency of the system need to be addressed, the system shows promise in its
      ability to make useful flight safety information available to all pilots in order
      to save lives.

PMID- 9262819
TI  - Incorporating occupational medicine methodology into military fitness for duty
      and readiness issues.
AB  - The need for the U.S. Air Force (USAF) to know its personnel's fitness for duty
      and readiness status is one of the most significant criteria for determining
      their ability to complete the missions assigned to them. This is especially
      critical in the current milieu of increasing deployments. However, the USAF has a
      very limited program to meet this need. Occupation Medicine has had extensive
      experience in determining job requirements, assessing individuals, and monitoring
      performance over time. Further integrating Occupational Medicine methodology and
      the current state of scientific knowledge on physical performance is advocated to
      improve the USAF's ability to have a fit and ready force able to meet its
      burgeoning mission. This paper reviews the literature with the following
      recommendations: a) assess the physical fitness of the force given future demands
      due to readiness taskings and if necessary mandate individual and unit exercise
      and provide time for these activities; b) eliminate the weight management and
      cycle ergometry programs; c) establish physical fitness standards appropriate for
      each job as well as for initial entry into the USAF, these standards should
      incorporate ongoing testing, evaluation, and training; d) body fat should be
      treated only as a medical condition and not as an image standard; and e)
      establish case management teams to optimize the identification, treatment, return
      to duty and medical boarding of personnel with injuries or subpar performance.

PMID- 9262820
TI  - Are human subject volunteers still players in aeromedical research as we enter
      the 21st century?
AB  - The U.S. Air Force has enjoyed the luxury of having dedicated human volunteer
      subjects for sustained and impact acceleration research for over 50 yr. However,
      with today's world economy and budgetary cutbacks, this may no longer be a viable
      option. The onslaught of advanced medical technology, combined with an increasing
      performance envelope for aircraft and their ejection systems, have created an
      environment where the validity of research data and the ethics of human-use
      research are being challenged. Now is an opportune time to reevaluate the way
      human-use aeromedical research is conducted. The validity of using nonpilots in
      lieu of pilots in aeromedical research is discussed in light of the following: a)
      the increased emphasis on performance metrics within sustained acceleration; b)
      the matching of human subjects (nonpilots) to pilots in the appropriate
      attributes to ensure validity of data; c) degree of medical screening required
      given the ethics of human-use research and concerns of pilots; and d) the
      challenge of evaluating the "value added" of new technology for medical
      screening. It is concluded that volunteer panels should be maintained with
      nonpilots matched with pilots physically and psychologically such that
      operational performance characteristics are similar. Medical screening should be
      similar so that research data from subjects can be applied to the target
      population (pilots). Longitudinal data collection (e.g., spinal X-rays) on pilots
      would also be of great value as a basis for studying the occupational hazards of
      flying.

PMID- 9262821
TI  - Outcome from neurological decompression illness.

PMID- 9262822
TI  - Material optimisation of the femoral component of a hip prosthesis based on the
      fatigue notch fatigue approach.
AB  - Previous studies have optimised the shape of a cemented stainless steel stem in
      order to minimise the fatigue notch factor Kf in the cement whilst at the same
      time maximising Kt in the proximal medial bone to prevent bone resorption [1].
      The present study firstly describes the effect of changes in the modulus of
      elasticity of the stem material for both the original Charnley stem and the
      optimised shape on Kf as predicted by a 2D finite element (FE) model of the
      implanted prosthesis. The paper further describes a method for parametric
      optimisation to determine the best material properties of a layered composite
      femoral stem consisting of a core material (stainless steel) and an outer layer
      of a different material, the elastic modulus of which is used as a design
      variable. The overall objective of the optimisation was to maximise Kf in the
      proximal bone whilst at the same time constraining Kf at all cement interfaces to
      be no greater than its initial value. The results of the first study suggest that
      Young's moduli of about 145 and 210 GPa are optimal for the monolithic Charnley
      and optimised stems, respectively. A composite prosthesis with a layer of modulus
      31 GPa added to the optimised stainless steel stem in the proximal region only
      was found to significantly increase the stresses in the proximal bone and reduce
      Kf in the cement whilst retaining the advantages of an outer stem profile very
      similar to that of the original Charnley prosthesis.

PMID- 9262823
TI  - Non-linear large deformation FE analysis of orthodontic springs.
AB  - Large deformation non-linear finite element models of T, V, L and B (Baldwin)
      orthodontic springs were developed and experimentally validated. Spring
      stiffnesses and moment/force ratios were computed. Compared to the T loop, under
      horizontal activation, the V loop was half as stiff, the L loop was equal, and
      the B spring was 10% as stiff. The moment/force ratio was 30% higher in the V
      configuration, while the B spring was less by 95%. The asymmetric L loop exerted
      a moment/force ratio that was 30% on the one side, but 180% in the opposite
      direction on the other side. With vertical activation, also compared to the T
      spring, the horizontal stiffnesses were 500% (V), 150% (L), and 30% (B). The
      concomitant vertical stiffnesses were 100%, 50% and 25%. The vertically activated
      moment/force ratios were nearly equal in the four springs. Experiments validated
      these FEM calculations.

PMID- 9262824
TI  - On the three-point flexural tests of dental polymeric resins.
AB  - Currently acrylic resins are commonly employed in many medical applications,
      especially for the fabrication of long span provisional restorations in dentistry
      and bone cement in orthopedics. On of the major problems associated with the
      conventional type of acrylic resins is their unsatisfactory mechanical
      properties. Among many attempts to strengthen acrylic resins, it has been
      demonstrated that they can be strengthened through the addition of
      reinforcement(s) as structural components of different size, shape and chemical
      composition, dispersed in the acrylic matrix, thus forming a composite structure.
      In the course of studies to strengthen dental polymeric resins by admixing
      various metallic oxide particles, PMMA-, PEMA-, and PIMA-based resins were
      reinforced by 2 vol.% added alumina, magnesia, zirconia, and silica powders. It
      was found that PMMA admixed with 2 vol.% zirconia exhibited the best improvement
      of mechanical properties (breaking strength, modulus of elasticity, offset yield
      strength, and fracture toughness as well). All tests were conducted under three
      point bending. It was also found that the breaking strength based on the original
      sample dimension was, at most 20% less than those based on the final sample
      dimension. Moreover, this discrepancy was independent of the type of tested
      material, but dependent on the sample's modulus of elasticity.

PMID- 9262825
TI  - Biomechanical evaluation of hydroxyapatite intervertebral graft and anterior
      cervical plating in a porcine cadaveric model.
AB  - The biomechanical properties of a porous hydroxyapatite (HA) intervertebral graft
      with or without anterior cervical plating were evaluated in cadaveric porcine
      cervical spine model using C3-4 discectomy and dissection of the posterior
      longitudinal ligament to cause instability. The experimental groups were intact
      (n = 11), instability (n = 11), autogenous bone implant (n = 6), HA graft implant
      (n = 5), autogenous bone with plating (n = 6), and HA graft with plating (n = 5).
      Porous HA with 40% porosity and scapular bone were used as grafts. The
      displacement rates of the cervical spine by compressive forces in the flexural,
      extensional, and lateral bending directions were evaluated using video-recording
      followed by computer-assisted analysis. The stiffness to compressive load was
      calculated from the load-displacement rate curve. The linear and non-linear
      coefficients of the Fung's equation were obtained based on the plot of Young's
      modulus against load. There were no statistical differences in the stiffness
      between the HA and autogenous bone graft in all directions. The two plating
      groups showed significantly increased stiffness in all directions. The non-linear
      coefficient value in Fung's equation was far larger in both HA and HA graft with
      plating groups than in the other groups in flexural compression. Porous HA graft
      has a compressive strength similar to autogenous graft in vitro, and anterior
      plating provides additional stiffness to the cervical spine. The larger non
      linear coefficient value of the HA groups may represent the characteristic
      biomechanical brittleness of HA graft, but this is manifest only in flexural
      compression.

PMID- 9262827
TI  - Heterogeneous fluoridated hydroxyapatites partially substituted with fluoride
      ions.
AB  - The partially substituted fluoridated apatites H-FHAp0.5 and FH-HAp0.5 were
      synthesized heterngeneously by supplying fluoride at a concentration equivalent
      to half of the maximum value of fluorapatite during the initial or final half of
      the experimental period. Although X-ray diffraction patterns and SEM photos of H
      FHAp0.5 and FH-HAp0.5 apatites were not significantly different, high-resolution
      electron microscopy showed quite different features; H-FHAp0.5 type apatite was
      an elongated hexagon with electron beam damage in the core, and FH-HAp0.5 type
      apatite was a rather wide hexagon analogous to fluorapatite. Energy dispersive
      spectroscopy attached to the SEM showed H-FHAp0.5 apatite to have a higher
      fluoride peak intensity than FH-HAp0.5. These results supported the previous
      speculations on the two different types of heterogeneous fluoridated
      hydroxyapatites: hydroxyapatite covered with fluorapatite and fluorapatite
      coverted with hydroxyapatite.

PMID- 9262826
TI  - Hydroxyapatite impregnated bone cement: in vitro and in vivo studies.
AB  - Hydroxyapatite (HA) particle impregnated polymethylmethacrylate (PMMA) bone
      cement was fabricated in order to induce bony tissue ingrowth into the pores left
      behind by resorption of the HA. The amount of HA was 0%, 10%, and 30% by weight.
      After mixing the HA with bone cement it was cast in a 4 mm inside diameter glass
      tube (10 mm long). Each specimen was cut into half and used for in vitro and in
      vivo experiment. Diametral tensile and flexural bend tests were made to evaluate
      its mechanical properties. SEM (scanning electron microscope) and ESCA (electron
      spectroscopy for chemical analysis) were used to evaluate the surface
      characteristics of the specimen. Push-out test and histology studies were made
      after implanting the specimens for six weeks in the distal portion of rabbit
      femur. The mechanical test results showed significant decrease of the flexural
      and diametral tensile strength linear with the increased amount of HA (p < 0.05).
      The SEM and ESCA analyses showed no definite exposure of HA particles on the
      surface of the specimens due to the covering by PMMA. The interfacial shear
      strength of the implanted specimens showed significant increases in the 30% HA
      specimens compared with the 0% ones but the 10% specimens did not show any
      difference. Histological observation showed little HA particle apposition to new
      bone in 10% specimens but more in the 30% ones. In conclusion, this study showed
      the decreased mechanical properties both by increasing the amount of HA particles
      and with the bone particles impregnated bone cement. In vivo study showed much
      lower interfacial shear strength due to implant site compared to other studies
      but the 30% HA specimens showed statistically significant increase in the push
      out strength after implanting into the distal end of rabbit femora.

PMID- 9262828
TI  - Mechanical evaluation of humeral interlocking intramedullary nails.
AB  - Implantation of an interlocking intramedullary nail has rapidly become the
      modality of choice for the management of various fractures of the humeral shaft;
      namely, those that are not minimally displaced, impacted and/or stable. The
      mechanical properties of the nail per se or the nail-bone construct are essential
      to the nail's satisfactory clinical performance. The present work is a critical
      review of this topic, using reports given in the opne literature. Whence, gaps
      and unresolved controversies in the current knowledge base are identified.
      Expositions on future work, based on the foregoing observations as well as
      uncharted topics, are presented.

PMID- 9262830
TI  - A viscoelastic material model to represent smooth muscle shortening.
AB  - The mechanical properties of a contracting smooth muscle can be changed by
      changing its length. A viscoelastic material model was developed to predict the
      length-dependent stiffness changes when a constrained muscle is allowed to
      shorten under a constant external force. Three-dimensional finite element
      simulations were carried out to estimate the stiffness changes and compared to
      available experimental data. A good agreement was found indicating that the
      viscoelastic material model developed gives a valid representation of the length
      dependent stiffness changes of a smooth muscle. Sensitivity analysis was carried
      out to determine the relative effects of material constants in the model on the
      length dependent stiffness.

PMID- 9262829
TI  - Residual stresses in the human aorta and their influences by growth and
      remodelling.
AB  - The aim of the present work is to demonstrate of the influence of the adventitia
      on distribution of residual stresses in the human aorta. The biomaterial increase
      in media as well as in adventitia in the course of the aorta's growth is formed
      by an intussusceptive mechanism of growth. In children's aortas, formative
      elastin lamellae are wavy with high amplitude perpendicular to the aortic
      surface. In adults' aortas the waves become smoother (stepwise) towards the
      adventitia. Also introduced is the growth function, which characterizes the
      biomaterial growth and the interference between the media and adventitial layers.
      It is possible to expect an extraordinary variability in the formation of the
      aortic wall tissue in the course of its growth as a result of metabolic and
      humoral influences and magnitude of the residual stresses in the course of
      growth.

PMID- 9262831
TI  - A constitutive modeling of the human lumbar intervertebral disc and forward
      backward bending simulation.
AB  - This paper presents a constitutive law of the lumbar intervertebral disc to be
      described mathematically with the finite deformation theory. Mechanical behavior
      of the cadaveric lumbar disc obtained from continuous cyclic compression-tension
      tests and continuous cyclic axial torsion tests was formulated by the
      constitutive equation with a semi-circular shaped model. These equations were
      formulated with or without taking the nucleus pulposus into account. It was also
      confirmed that forward-backward bending behavior of the disc could be simulated
      numerically from these equations.

PMID- 9262832
TI  - Bone stiffness changes due to microdamage under different loadings.
AB  - Stiffness changes due to microdamage in the longitudinal and cross-sectional
      directions in a dog bone model under different loadings were investigated using
      three-dimensional finite element analysis. Stiffness changes and severity of both
      longitudinal and cross-sectional type microcracks were estimated between the
      damaged and undamaged bone under four-point bending, torsion and tension. Finite
      element simulation results indicated that longitudinal damage was more severe
      than cross-sectional damage under axial tension and bending, and the opposite was
      true for torsional loading. However, for axial tension, the stiffness change due
      to cross-sectional microcracks remained constant.

PMID- 9262833
TI  - Effect of the archwire slot profile on the performance of bonded orthodontic
      brackets.
AB  - The finite element analysis method and a two-dimensional idealization were used
      to conduct a parametric study of the effect of the archwire slot (or insert)
      profile on the stresses in, deformation of, and efficiency of a model of a bonded
      edge-wise "combination-materials" type of orthodontic bracket. The results are
      consistent with a priori expectations and are qualitatively the same as those
      obtained by previous workers who used the two-dimensional photoelasticity stress
      analysis method. The results thus highlight a possible approach to improving the
      clinical performance of these brackets.

PMID- 9262834
TI  - Metallic ion release in artificial saliva of titanium oral implants coupled with
      different metal superstructures.
AB  - In this work the metallic ion release in oral implants with superstructures of
      different metals and alloys used in clinical dentistry has been determined. This
      study has been realized in a saliva environment at 37 degrees C. The measurements
      of the ion release were carried out by means of the Inductively Coupled Plasma
      Mass Spectrometry technique. The titanium oral implant coupled with a chromium
      nickel alloy releases a high quantity of ions and the implant coupled with the
      titanium superstructure presents a low value of ion release.

PMID- 9262835
TI  - Technology acquisition strategies for clinical engineering.

PMID- 9262836
TI  - In vitro testing of pacemakers for digital cellular phone electromagnetic
      interference.

PMID- 9262837
TI  - Feasibility study of a single- and multiple-source near-infrared phase-modulation
      device for characterizing biologic systems.
AB  - Near-infrared (NIR) spectroscopy is an inexpensive and noninvasive optical method
      to characterize biologic and physiologic systems. Measurements of oxygen
      saturation in various organs, cytochrome oxidase concentration, and glucose
      concentration in tissue are examples of NIR spectroscopy applications. This
      instrument also has potential for diagnostic imaging by comparing the optical
      properties of a given point in tissue with those of the surrounding areas, e.g.,
      tumor localization, hematoma detection, or deep vein thrombosis detection.
      Currently, NIR spectroscopy is available in three modalities: time-resolved
      spectroscopy (TRS), continuous-wave spectroscopy (CWS), and a phase-modulation
      device. This paper describes a single-source phase-modulation device and a
      multiple-source (in- and anti-phased) device and their application to system
      identification. The phase and intensity information for homogeneous systems is
      correlated with system and instrumental parameters. Phase and intensity changes
      resulting from the presence of one and two absorbers are illustrated. The
      sensitivity of in- and anti-phased phase-modulation devices (phased arrays) is
      demonstrated. The use of amplitude-modulated phased array for heterogeneity
      detection is described.

PMID- 9262838
TI  - The use of two or more microorganisms versus one microorganism in the carrier
      materials for biological indicators.
AB  - Specification for the preparation of a biological indicator (BI) using two or
      more microorganisms in the carrier material were deleted from the current ISO
      11138 series and Working Draft 14161 because it was assumed that the resistances
      of the individual microorganisms would be affected by interference from the other
      microorganisms. This assumption is speculative only, and has not been supported
      by experimental evidence. To test its validity, the author carried out an
      experiment to determine the resistances of Bacillus subtilis and Bacillus
      stearothermophilus when used alone and together in BI carrier material. In total
      concentrations of 10(6) cfu/0.1 mL, the organisms were applied alone and together
      to filter paper and dried. After incorporation into the BI, the three
      preparations (B. subtilis alone, B. stearothermophilus alone, and both together)
      were subjected to ethylene oxide sterilization or to moist-heat sterilization
      using the procedures described in ISO 11138-2 or ISO 11138-3, respectively.
      Resistances were measured in terms of decimal reduction times (D values). The D
      values of the preparations were determined using the survival-curve method and
      the limited Spearman-Karber method in conjunction with a BI evaluator
      resistometer. The D values of the preparations did not differ significantly with
      either sterilization method, providing experimental evidence that, at least under
      these conditions, the presence of a second microorganism in the carrier material
      did not interfere with the resistance of the original microorganism.

PMID- 9262839
TI  - Unconstrained heart-rate monitoring during bathing.
AB  - An unconstrained electrocardiograph (ECG) and heart-rate monitor was designed to
      record ECG measurements in the bathtub. The apparatus consists of analog and
      digital parts. In the analog part, electrocardiographic signals obtained from
      electrodes placed inside the bathtub were amplified approximately 4,000 times.
      The electrodes were made of stainless steel and were 104 x 74 x 0.5 mm in size,
      including the absorbent sponge covers. Each electrode fitted into a plastic case
      110 x 79 x 23 mm in size. Working electrodes were placed 20 cm from the bottom of
      the long bathtub wall, close to the position of the immersed trunk, and a
      reference electrode was placed 5 cm from the bottom of the side wall close to the
      toe position. In the digital part of the system the heart rate was calculated
      from the R-R interval of each ECG pulse and the calculated data were stored in a
      random-access memory. These stored data were transferred to a personal computer
      through an RS 232C interface and analyzed. The heart rates obtained from the
      bathtub ECG agreed with those obtained from a body-surface ECG. During
      measurements in bathwater with various concentrations of sodium chloride, the
      amplitude of the electrocardiographic waveform decreased as the electrical
      conductivity increased. The frequency characteristics of the bathtub ECG varied
      with the bathtub dimensions and the electrical conductivity of the water. Using
      this apparatus, heart-rate measurements can be obtained easily and noninvasively,
      but interpretation of the ECG signal requires great care. This monitor could be
      used as a home health heart-rate monitor.

PMID- 9262840
TI  - Mechanical prosthetic heart valves.

PMID- 9262841
TI  - Dialysis.

PMID- 9262842
TI  - Equations for the calculation of the protein catabolic rate from predialysis and
      postdialysis urea concentrations and residual renal clearance in stable
      hemodialysis patients.
AB  - Several simple equations exist for the calculation of K1/V from predialysis
      (Cpre) and postdialysis (Cpost) measurements of urea concentration. Analogous
      equations are needed for precise determination of patients protein catabolic rate
      (nPCR) from Cpre and Cpost. In this study we develop three simple nPCR equations
      from urea mass balance theory. The equations, which include a term for residual
      function, may be applied to any session of the week for patient dialyzed three
      times weekly who are in steady state with respect to dialysis dose and protein
      catabolism. The precision of each equation was tested with Cpre Cpost data
      obtained from steady state simulations of 540 patients without residual renal
      clearance (KR) and 972 simulated patients with significant residual KR. The
      simplest equation has the form: [formula: see text] where V is urea distribution
      volume and a and d are constants varying with session of the week. When compared
      to nPCR values calculated from formal urea kinetic modeling, the error determined
      with this formula never exceeded 5% for the midweek or final session. A more
      complicated equation of the form: [formula: see text] provided nPCR estimates
      with a maximum error < 1.3% for any dialysis session of the week and for KR up to
      4 ml/min for a 70-kg patient. The only data required for the latter equation are
      Cpre, Cpost, length of dialysis session, volume ultrafiltered (delta BW), and an
      approximate value of the patient's urea distribution volume. The proposed
      equations permit nPCR to be calculated simply and accurately for stable patients
      dialyzed three times a week.

PMID- 9262844
TI  - Effects of LDL apheresis on blood rheology in two patients with homozygous
      familial hypercholesterolaemia.
AB  - Changes in haemorheological and lipid variables were investigated in 2 patients
      with homozygous familial hypercholesterolaemia (FH) treated with low-density
      lipoprotein (LDL) apheresis using dextran sulphate adsorbent. The immediate
      effect of LDL apheresis was a fall in plasma fibrinogen by 50%, total and LDL
      cholesterol by 60%, plasma viscosity by 12% and whole blood viscosity by 17%.
      Before the 12th treatment session, plasma fibrinogen concentration remained
      reduced by 22%, whole blood viscosity by 17% and the plasma viscosity by 11%
      compared with the initial values. Total and LDL cholesterol in plasma also
      remained reduced by about 50%. We conclude that LDL apheresis, using dextran
      sulphate adsorbent, improves blood rheology. The decrease in plasma fibrinogen
      concentrations, plasma viscosity and LDL cholesterol might be factors
      contributing to the improved haemorheological properties.

PMID- 9262843
TI  - On-line predilution hemofiltration versus ultrapure high-flux hemodialysis: a
      multicenter prospective study in 23 patients. Sardinian Collaborative Study Group
      of On-Line Hemofiltration.
AB  - The aims of the present prospective multicenter study were to assess the clinical
      tolerance and well being, the correlation between nPCr and Kt/V and the
      pretreatment beta 2-microglobulin level in patients sequentially treated with
      high-flux dialysis with ultrapure bicarbonate hemodialysis (HD; phase 1) and
      predilution hemofiltration (HF) with on-line prepared bicarbonate substitution
      fluid (phase II). The same monitor (Gambro AK 100 ULTRA) and membrane (polyamide)
      were used. Twenty-three patients, all in a stable clinical condition, entered the
      study. The treatment was targeted to an equilibrated Kt/V (eqKt/V) of 1.4 for HD
      and 1.0 for HF. No mortality or relevant morbidity were observed. The number of
      hypotensive episodes was 1.78 +/- 2.8 per patient and month during HD vs. 1.17 +/
      3.1 during HF (p = 0.003) and the number of the hypertensive episodes 1.28 +/-
      2.8 during HD vs. 0.42 +/- 0.8 during HF (p = 0.04). Incidences of arrhythmia,
      muscular cramps and headache were significantly less frequent during HF.
      Interdialytic cramps, arthralgia and fatigue were also significantly less
      frequent during the HF period. The average beta 2-microglobulin level was 27.1 +/
      14.7 mg/dl at the start of the study, 22.9 +/- 4.9 mg/dl at the beginning of
      phase II and 22.4 +/- 4 mg/dl at the end of phase II (p = 0.01 compared to the
      start). A significant linear correlation between the normalized protein catabolic
      rate and eqKt/V was obtained faster during HD than during HF (45 vs. 120 days)
      indicating that HF affects the nutritional status with mechanisms different from
      HD. The present study is in agreement with the hypothesis that HF gives and
      adequate nutritional status with improved clinical stability and well being at a
      lower Kt/V compared to HD. Both therapies were efficient in controlling the
      pretreatment beta 2-microglobulin level.

PMID- 9262845
TI  - Chlorine dioxide: a new agent for dialysis monitor disinfection in a pediatric
      center.
AB  - In order to evaluate the bacterial and endotoxin contamination in the dialysis
      fluids of our pediatric center and the effectiveness of chlorine dioxide (CD)
      compared with a conventional method, (1) deionized water, (2) dialysate fluid,
      (3) basic concentrate, and (4) acid concentrate were tested in 4 dialysis
      machines. Monitor sterilization was made using CD in protocol A and sodium
      hypochlorite/acetic acid in protocol B. Once every 2 weeks the deionized water
      set of distribution was routinely disinfected with peracetic acid. Each protocol
      lasted 1 months and the samples were taken, under aseptic conditions, on the
      15th, 22nd and 27th day. All samples, at all stages of the study, showed an
      endotoxin concentration below the limits recommended by the Canadian Standard
      Association. Fifty-nine out of 72 samples in A and 62 out of 72 samples in B
      showed a bacterial count within the range recommended by the Association for the
      Advancement of Medical Instrumentation. The data show that both protocols
      produced the same results. However, protocol A is to be preferred for its
      simultaneous disinfecting-cleaning and descaling activity which proves time
      saving.

PMID- 9262846
TI  - Viral hepatitis in continuous ambulatory peritoneal dialysis patients in an
      endemic area for hepatitis B and C infection: the Taiwan experience.
AB  - The prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), and their
      associations in 64 continuous ambulatory peritoneal dialysis (CAPD) patients (30
      males and 34 females) were evaluated. A comparison was also made with 526 normal
      controls (266 males and 260 females). Forty-seven (75%) CAPD patients were anti
      HBc positive, with no significant difference to the control group (81.9%). This
      probably reflects acquisition of HBV infection by CAPD patients before initiation
      of chronic dialysis therapy in a region hyperendemic for HBV. On the contrary, 11
      (17.2%) CAPD patients were anti-HCV positive and 8 (15.2%) were seropositive for
      both anti-HBc and anti-HCV-much greater prevalence rates compared to those of the
      control group. The prevalence of anti-HCV correlated with the history and numbers
      of blood transfusion, and the length of time on previous hemodialysis. A similar
      correlation occurred in patients with both anti-HBc(+) and anti-HCV(+). In
      conclusion, in an HBV endemic area such as Taiwan, the prevalence of coexisting
      HBV and HCV infection in CAPD patients depends on the latter.

PMID- 9262847
TI  - Heparin-free hypothermal hemodialysis at 20 degrees C improves biocompatibility.
AB  - We investigated the effect of cooling blood to 20 degrees C on the reactions and
      dialysis efficiency in a model using pigs. Eighteen uremic pigs were
      hemodialyzed. Nine pigs were hemodialyzed cooling the blood in the dialysis
      filter and rewarmed using microwaves to body temperature before being returned to
      the pigs; no heparin was added. Nine pigs (control group) were dialyzed using
      heparin without blood cooling. A significant decrease in the number of leukocytes
      was observed after 15 min in the control group, whereas no change was observed in
      the hypotherm-dialyzed group. We conclude that heparin-free hemodialysis
      performed at 20 degrees C with microwave rewarming is possible, improving
      biocompatibility significantly.

PMID- 9262848
TI  - Assessment of the effects of low dialysate flow rates on removal rates and
      clearance using high flux membranes.
AB  - The effects of the low dialysate flow rates on the removal rate and clearance of
      urea nitrogen, creatinine, uric acid, beta 2-microglobulin and myoglobin, using
      high flux membranes were studied. The removal rates for all substances were not
      significantly decreased. Although clearance of urea nitrogen, creatinine and uric
      acid was significantly decreased (p < 0.05), clearance of inorganic phosphate,
      beta 2-microglobulin and myoglobin was not significantly decreased. These results
      suggest that hemodialysis at low dialysate flow rates for a short term during
      water shortages due to natural disasters and drier climates can be performed with
      an insignificant reduction in removal rates and a minimum reduction in clearance.

PMID- 9262849
TI  - Computer models of language disorders.

PMID- 9262850
TI  - Neuropragmatics: neuropsychological constraints on formal theories of dialogue.
AB  - We are interested in the validation of a cognitive theory of human communication,
      grounded in a speech acts perspective. The theory we refer to is outlined, and a
      number of predictions are drawn from it. We report a series of protocols
      administered to 13 brain-injured subjects and to a comparable control group. The
      tasks included direct and indirect speech acts, irony, deceits, failures of
      communication, and theory of mind inferences. All the predicted trends of
      difficulty are consistently verified; in particular, difficulty increases form
      direct/indirect speech acts to irony, from irony to deceits, and from deceits to
      failure recovery. This trend symmetrically shows both in the successful situation
      and in the failure situation. Further, failure situations prove more difficult to
      handle than the relevant successful situation. In sharp contrast with previous
      literature, there is no difference between the subjects' comprehension of direct
      and indirect speech acts. The results are discussed in the light of our
      theoretical approach.

PMID- 9262851
TI  - An anatomically structured sensory-motor sequence learning system displays some
      general linguistic capacities.
AB  - The capacity in primates to master temporal-sequential constraints from the
      external world might provide a basis for accommodating similar constraints in
      language. While the neural specialization required for language clearly
      distinguishes man from the other primates, it is less clear to what extent this
      specialization constitutes a drastic neurophysiological divergence versus a
      variation on an existing sequencing capability. In an effort to address this
      issue, an anatomically structured neural network model, previously developed to
      reproduce complex sensory-motor sequences and the corresponding single-unit
      recordings from primate prefrontal cortex, is studied in a simple linguistic
      context. The model is presented sentences from a small language and demonstrates
      a simple capacity to "understand" and generalize at different levels.
      Interactions between variations on (a) the model architecture and (b) the target
      language structure agree with data from crosslinguistic aphasia studies. These
      results support the hypothesis that a brain architecture for nonlinguistic
      cognitive functions (in this case sensory-motor sequencing) can provide a basis
      for a general sequence processing component of linguistic function.

PMID- 9262852
TI  - Aphasic sentence comprehension as a resource deficit: a computational approach.
AB  - This article describes a new computational model of aphasic sentence
      comprehension. The model is based on the premise that all aphasics, however
      different, share a common deficit which determines a considerable amount of the
      individual variation observed in their sentence comprehension performance. This
      common deficit is construed as a pathological reduction in the activation
      resources of a working memory system that subserves sentence comprehension
      (Miyake, Carpenter, & Just, 1994). To test the theoretical feasibility of the
      resource reduction hypothesis, a new computer model of aphasic sentence
      comprehension was developed and tested. We describe the model as well as some
      initial simulation results, indicating that the model can account for some of the
      sentence complexity and severity effects that have been reported in the aphasia
      literature.

PMID- 9262853
TI  - An artificial life approach to language.
AB  - The aim of the paper is to show that an Artificial Life approach to language
      tends to change the research agenda on language which has been shared by both the
      symbolic paradigm and classical connectionism. Artificial Life Neural Networks
      (ALNNs) are different from classical connectionist networks because they interact
      with an independent physical environment; are subject to evolutionary,
      developmental, and cultural change, and not only to learning; and are part of
      organisms that have a physical body, have a life (are born, develop, and die),
      and are members of genetic and sometimes, cultural populations. Using ALNNs to
      study language shifts the emphasis from research on linguistic forms and
      laboratory-like tasks to the investigation of the emergence and transmission of
      language, the use of language, its role in cognition, and language as a
      populational rather than as an individual phenomenon.

PMID- 9262854
TI  - A parallel licensing model of normal slips and phonemic paraphasias.
AB  - A model of phonological processing in speech production based on prosodic
      licensing can capture general patterns of errors found in both normal and aphasic
      speech. All segments must be licensed by some prosodic category (syllable,
      nucleus, or rime) in order to be produced. Constraints on licensing, including
      both phonotactic and binding constraints, ensure that only correct licensing
      associations are retained. A computer simulation of our model produces utterances
      in qualitative agreement with human speech error data. Phonemic puraphasias are
      claimed to arise from the same mechanisms as normal speech errors; the difference
      being only a matter of disturbance of the lexical retrieval and licensing
      processes. The fact that these errors, which can involve gross disruption of the
      segmental sequence, still produce phonotactically well-formed strings is a direct
      consequence of the syllabic licensing that forms the core of our theory of speech
      production.

PMID- 9262855
TI  - Ethicist's second commentary on the case of the stray tattooed beagle.

PMID- 9262856
TI  - Canadian veterinarians in The Netherlands.

PMID- 9262857
TI  - Ecosystem health as a clinical rotation for senior students in Canadian
      veterinary schools.
AB  - We describe 4 years of an experimental rotation in ecosystem health offered to
      senior veterinary students in Canada. Faculty from the 4 Canadian veterinary
      colleges collaborated in offering the rotation once annually at 1 of the
      colleges. The 1st rotation was held in Guelph in 1993, followed in successive
      years by rotations at Saskatoon, Saint-Hyacinthe, and Charlottetown. The rotation
      is a predominantly field-based experience that allows students to work with
      veterinary and other role models who are actively engaged in clinical research
      related to ecosystem health. Five specific field studies that worked particularly
      well during the rotations are presented. These studies involved investigating
      mortality in wildlife due to botulism, designing an environmental surveillance
      system around herds of beef cattle, using belugas to evaluate the health of the
      St. Lawrence River, dealing with competition for water use by aquaculture and
      agriculture, and exploring the role of veterinarians during major coastal oil
      spills. The experience has resulted in our developing the subject matter, field
      examples, teaching approach, and confidence necessary to make ecosystem health
      the focus of a productive clinical rotation for senior year veterinary students.

PMID- 9262858
TI  - Focal myasthenia gravis in a dog.
AB  - A 10-month-old American cocker spaniel was evaluated for megaesophagus,
      aspiration pneumonia, but no appendicular muscle weakness. During
      hospitalization, weakness of the facial muscles developed, this resolved with
      anticholinesterase administration. Serum antibodies against acetylcholine
      receptors were documented, confirming the diagnosis of focal myasthenia gravis.
      Diagnosis, management, and medical treatment are discussed.

PMID- 9262859
TI  - Copper toxicity in confinement-housed ram lambs.
AB  - Fourteen Suffolk rams (6 mo) were diagnosed with chronic copper poisoning.
      Preliminary results indicated that a combination of serum aspartate
      aminotransferase, gamma glutamyltransferase, and copper could be used as a test
      so that high risk lambs could be treated more aggressively.

PMID- 9262860
TI  - Combination of medical and surgical therapy for pleuropneumonia in a horse.
AB  - Medical management was unable to prevent the development of an extrapulmonary
      abscess in a 10-year-old Thoroughbred gelding with anaerobic pleuropneumonia.
      Intercostal thoracostomy achieved drainage of the abscess. Resolution of the
      abscess and subsequent bronchopleural fistulas was monitored by ultrasonography
      and video-endoscopy. The horse returned to training 4 mo after discharge.

PMID- 9262863
TI  - Combating hypothermia, including recommendations for the use of oat bags.

PMID- 9262861
TI  - Trichophyton dermatophytosis--a disease easily confused with pemphigus
      erythematosus.
AB  - Trichophytosis is a rare diagnosis in dogs in Ontario, but recently 4 dogs with a
      scaling and crusting, alopecic, facial dermatitis have been so diagnosed. In all
      cases, the histopathological findings of severe epidermal and follicular
      interface dermatitis, accompanied by an acantholytic intraepidermal pustular
      dermatitis suggested an immune-mediated disease.

PMID- 9262862
TI  - Leptospirosis in 2 unrelated dogs.

PMID- 9262864
TI  - Diagnostic ophthalmology. Hypertensive retinopathy.

PMID- 9262865
TI  - Effect of metabolic inhibitors on membrane potential and ion conductance of rat
      astrocytes.
AB  - 1. The aim of this study was to elucidate the effect of metabolic inhibition on
      the membrane potential and ion conductance of rat astrocytes. The metabolic
      inhibitors investigated were dinitrophenol (DNP), carbonyl cyanide p
      trifluoromethoxyphenyl hydrazone (FCCP), cyanide, and oligomycin. 2. Primary
      cultures of astroglial cells from newborn rat cerebral cortex were cultivated for
      13-20 days on chamber slides. The effect of metabolic inhibitors on the cellular
      ATP concentration was estimated from the decrease in peak chemiluminescence from
      the luciferin/luciferase reaction. The membrane potential and ion conductances
      were measured from whole-cell recordings with the patch-clamp technique. 3. After
      2.0 min of incubation ATP decreased from the control level to 43% with cyanide (2
      mM), 58% with DNP (1 mM), 47% with FCCP (1 microM), and 69% with oligomycin (10
      microM). 4. Under normal conditions V was -74.4 +/- 1.0 mV. DNP and FCCP both
      caused a rapid and reversible depolarization equivalent to a shift in the I/V
      curve of 8.2 +/- 1.3 and 19.7 +/- 3.8 mV, respectively. DNP decreased the slope
      conductance (g) by 22.1% but FCCP had no significant effect on g. In contrast,
      neither oligomycin nor cyanide had any significant effect on the I/V curve. 5.
      Tetraethylammonium (TEA; 10 mM) depolarized the cells by 7.1 +/- 2.0 mV but had
      no significant effect on g. In the presence of TEA, DNP caused a depolarization
      of 52.8 +/- 3.5 mV and increased g by 45.5 +/- 9.6%. The action of FCCP was not
      affected by the presence of TEA. 6. Perfusion of the astrocytes with a Cl- free
      solution inhibited the action of DNP and FCCP. Thus the depolarization was only
      4.2 +/- 1.5 mV in DNP and 3.7 +/- 0.3 mV in FCCP, which were significantly
      smaller effects than in the presence of a high intracellular [Cl-]. 7. Block of
      tentative KATP channels with tolbutamide (1 mM) or Cl- channels with Zn2+ (1 mM)
      did not inhibit the depolarization caused by DNP or FCCP. 8. In conclusion, DNP
      and FCCP have specific effects on the plasmalemma in rat astrocytes which may be
      due to opening of Cl- channels. This effect was not seen with cyanide or
      oligomycin and should be considered as a possible complication when DNP and FCCP
      are used for metabolic inhibition.

PMID- 9262866
TI  - Expression of a quail bHLH transcription factor is associated with adrenergic
      development in trunk neural crest cultures.
AB  - 1. Expression of chick type 1 basic helix-loop-helix transcription factor
      GbHLH1.4 persists in several embryonic regions, including some where neural crest
      cells differentiate (Helms, J. A., et al., Mech. Dev. 48:93-108, 1994.) We have
      cloned portions of the quail homologue (designated QbHLH) in order to investigate
      its expression and possible function in quail neural crest cultures. Three sets
      of polymerase chain reaction primers were used to amplify cDNA sequences
      encompassing much of the coding region outside the bHLH domain. Two of the primer
      sets amplified a single band from all quail and chick tissues tested. The third
      set of primers produced two bands, differing by a 72-base pair insertion, both of
      which which were present in all tissues assayed. 2. The quail sequences showed
      greater than 97% nucleotide identity with GbHLH1.4. In situ hybridization of
      cultured quail neural crest cells showed expression in some, but not all, cells
      throughout the first 2 weeks in culture. 3. Tyrosine hydroxylase immunoreactivity
      correlated particularly well with QbHLH expression, although substantial
      subpopulations of cells with other phenotypes also express QbHLH. 4. In some
      cells, only limited regions of the cytoplasm showed hybridization with QbHLH
      probes, indicating possible mRNA localization. 5. The expression of QbHLH in
      neural crest cultures is consistent with its role as a relatively widely
      expressed helix-loop-helix dimerization partner and suggests that it may function
      by interacting with cell type-specific partners to regulate expression of genes
      involved in the development and maintenance of several phenotypes.

PMID- 9262867
TI  - Beta-adrenoceptors in the tree shrew brain. I. Distribution and characterization
      of [125I]iodocyanopindolol binding sites.
AB  - 1. The number and distribution pattern of beta-adrenergic receptors in the brain
      have been reported to be species specific. The aim of the present study was to
      describe binding of the beta-adrenoceptor ligand [125I]iodocyanopindolol in the
      brain of the tree shrew (Tupaia belangeri), a species which provides an
      appropriate model for studies of psychosocial stress and its consequences on
      central nervous processes. 2. 125I-Iodocyanopindolol (125ICYP) labeling revealed
      a high degree of nonspecific binding, which was due mainly to interactions of
      this ligand with serotonin binding sites. For a quantitative evaluation of beta 1
      and beta 2-adrenoceptors, serotonin binding sites had to be blocked by 100
      microM 5HT. 3. Binding of the radioligand to beta 1- and beta 2-adrenoceptors was
      characterized using the beta 1-specific antagonist CGP20712A and the beta 2
      specific antagonist ICI118.551. beta 1-adrenoceptor binding is present in the
      whole brain, revealing low receptor numbers in most brain regions (up to 1.5 to
      2.7 fmol/mg). A slight enrichment was observed in cortical areas (lateral orbital
      cortex: 4.0 +/- 0.7 fmol/mg) and in the cerebellar molecular layer (8.7 +/- 1.0
      fmol/mg). 4. Competition experiments demonstrated high- and low-affinity binding
      sites with considerable variations in Ki values for CGP20712A, showing that
      various affinity states of beta 1-adrenoceptors are present in the brain (Ki:
      0.61 nM to 67.1 microM). In the hippocampus, only low-affinity beta 1
      adrenoceptors were detected (Ki: 1.3 +/- 0.2 microM). Since it is known that
      125ICYP labels not only membrane bound but also internalized beta-adrenoceptors,
      it can be assumed that the large population of the low-affinity sites represents
      internalized receptors which may be abundant due to a high sequestration rate. 5.
      High numbers of beta 2-adrenoceptors are present in only a few brain structures
      of tree shrews (external layer of the olfactory bulb, 15.8 +/- 2.0 fmol/mg;
      claustrum, 19.3 +/- 1.5 fmol/mg; anteroventral thalamic nucleus, 19.4 +/- 1.5
      fmol/mg; cerebellar molecular layer, 55.0 +/- 4.3 fmol/mg). Also for this class
      of beta-adrenoceptors, high- and low-affinity binding sites for the beta 2
      selective antagonist ICI118.551 were observed, indicating that 125ICYP labels
      membrane bound and internalized beta 2-adrenoceptors. Only in the cerebellar
      molecular layer was a high percentage of high-affinity beta 2-adrenoceptors
      detected (Ki for ICI118.551 was 1.8 +/- 0.3 nM for 90% of the receptors). 6. In
      conclusion, beta 1- and beta 2-adrenoceptor binding can be localized and
      quantified by in vitro receptor autoradiography in the brains of tree shrews when
      serotonergic binding sites are blocked. Modulatory effects of long-term
      psychosocial conflict on the central nervous beta-adrenoceptor system in male
      tree shrews are described in the following paper.

PMID- 9262868
TI  - Beta-adrenoceptors in the tree shrew brain. II. Time-dependent effects of chronic
      psychosocial stress on [125I]iodocyanopindolol bindings sites.
AB  - 1. Stress in known to affect the functioning of the central noradrenergic system
      in a region-specific manner. The aim of the present investigation was to
      understand better the consequences of recurrent stressful experiences on central
      beta-adrenoceptors. 2. Alterations in the central nervous beta-adrenoceptor
      system resulting from different periods of psychosocial stress (PSS) were
      analyzed in male tree shrews (Tupaia belangeri) which were submitted to
      subordination stress for varying time periods. 3. In the first experiment, the
      whole number of beta-adrenoceptors was analyzed in the forebrains of subordinate
      animals and controls by in vitro autoradiography using 125I-iodocyanopindolol
      (125ICYP), while nonspecific binding of the radioligand to serotonin receptors
      was blocked with 100 microM 5HT. 4. PSS affects beta-adrenoceptors in a time
      dependent manner. A decrease in receptor affinity occurred after just 21 days of
      PSS in cortical areas and in the hippocampus, indicating stress effects on the
      conformation of beta-adrenoceptors. After 30 days of PSS, the numbers of beta
      adrenoceptors were significantly decreased in several cortical regions and in the
      olfactory area. 5. In the second experiment, we investigated the influence of PSS
      on both beta 1- and beta 2-adrenoceptors separately. 125ICYP binding was
      quantified in the presence of either ICI188.551 to block beta 2-adrenoceptors or
      in the presence of CGP20712A to block beta 1-adrenoceptors. 6. After 2, 10, 21,
      and 28 days of PSS, it become apparent that the two beta-adrenoceptor subtypes
      are regulated independently. Beta 1-adrenoceptors were transiently down-regulated
      after 2 days of PSS in the prefrontal cortex and in the olfactory area and were
      decreased after 28 days of PSS in the parietal cortex and the hippocampus. A
      transient up-regulation of beta 1-adrenoceptors occurred in the pulvinar nucleus
      after 10 days of PSS. Beta 2-adrenoceptors were transiently down-regulated after
      2 days of PSS in the prefrontal cortex and up-regulated in the pulvinar nucleus
      after 28 days of PSS. 7. These data demonstrate that chronic psychosocial stress
      in subordinate tree shrews leads to time-dependent changes in the central nervous
      beta-adrenoceptors system. 8. The high regional variability in stress-induced
      beta-adrenoceptor regulation is supposed to be due to the complex mechanisms of
      intracellular beta-adrenoceptor sequestration, which includes down-regulation
      and/or reinsertion of receptors into the plasma membrane. These mechanisms may be
      important components of the regulatory apparatus which enables the individual to
      adapt to situations of recurrent stressful experiences by balancing the central
      nervous adrenoceptor number.

PMID- 9262869
TI  - Modulation of glutamine synthesis in cultured astrocytes by nitric oxide.
AB  - 1. Previous results suggest that glutamine synthesis in brain could be modulated
      by nitric oxide. The aim of this work was to assess this possibility. 2. As
      glutamine synthetase in brain is located mainly in astrocytes, we used primary
      cultures of astrocytes to assess the effects of increasing or decreasing nitric
      oxide levels on glutamine synthesis in intact astrocytes. 3. Nitric oxide levels
      were decreased by adding nitroarginine, an inhibitor of nitric oxide synthase. To
      increase nitric oxide we used S-nitroso-N-acetylpenicillamine, a nitric oxide
      generating agent. 4. It is shown that S-nitroso-N-acetylpenicillamine decreases
      glutamine synthesis in intact astrocytes by approximately 40-50%. Nitroarginine
      increases glutamine synthesis slightly in intact astrocytes. 5. These results
      indicate that brain glutamine synthesis may be modulated in vivo by nitric oxide.

PMID- 9262870
TI  - Dueling hypotheses: circatidal versus circalunidian battle basics.
AB  - The circalunidian-clock hypothesis is a formulation describing the means by which
      the tide-associated rhythms of intertidal organisms are generated. The postulate
      was described in a 1995 article in this journal (12:299-310). A recent paper
      published here (13:153-62) by Prof. Ernest Naylor challenges the validity of this
      hypothesis and presents an alternate he calls the "circatidal/circadian clock
      hypothesis." His paper first presents a model of his idea and then expresses the
      model's action in an unusual type of plot of his own invention. From the latter's
      display, he concludes it describes all the properties used as supporting evidence
      for the circalunidian-clock idea and thus discredits that hypothesis. Here, I
      present my analysis of his model and discuss its usefulness to the field. I find
      that his Naylor plot does not represent his model, and that his hypothesis mainly
      explains only data he has obtained for his favorite research subject, the crab
      Carcinus. I built a model similar to his and show that it produces a compact plot
      nothing like the one he reported. Finally, I believe that the circalunidian-clock
      hypothesis-which was not at all endangered by the Naylor paper-is clearly the
      best explanation at this time for the control of organismic tide-associated
      rhythms.

PMID- 9262871
TI  - Circannual variation of cell proliferation in lymphoid organs and bone marrow of
      BDF1 male mice on three lighting regimens.
AB  - BDF1 male mice, which had been raised for several generations on a lighting
      regimen of LD 12:12, were studied. Experiments were conducted over 24 h spans
      during winter, spring, summer, and fall. For 3-4 weeks prior to each study, one
      third of the animals were kept on a lighting regimen of 8 h of light alternating
      with 16 h of darkness (LD 8:16), one-third was kept on a regimen of LD 12:12, and
      one-third was kept on a regimen of LD 16:8. Subgroups of mice on all three
      lighting regimens were killed at 4 h intervals over a 24 h span. At 20 minutes
      prior to sacrifice, the animals received 5 microCi of 3H-thymidine/0.2 ml/20 gm
      body weight intraperitoneally. The thymidine uptake in DNA (DPM[3H]/microgram
      DNA) was studied as an index of cell proliferation in the thymus, inguinal lymph
      node, spleen, femur, and a segment of the lumbar vertebral column. A circannual
      variation of 3H-thymidine uptake in DNA was found in all organs irrespective of
      the lighting regimen under which the animals were kept. The timing of the
      circannual variation, however, varied among the organs. In the thymus, the lowest
      thymidine uptake occurred during summer, with higher thymidine uptake during the
      other three seasons. In the inguinal lymph node, the peak in thymidine uptake was
      in the spring, with lower values during the other three seasons, the lowest
      during summer. In the spleen, the highest thymidine uptake occurred in the mice
      on all three lighting regimens during fall, with lower uptake during winter,
      spring, and summer. In the bone marrow of both the femur and the vertebral
      column, the thymidine uptake was high in winter and fall and low in spring and
      summer. Serum corticosterone measurements were available in winter, spring, and
      fall, and they showed statistically significant lower values in winter and fall
      than in spring. The conclusion was drawn that circannual rhythms of 3H-thymidine
      uptake in the DNA of the thymus, spleen, lymph nodes, and bone marrow are found
      in mice reared for generations under a LD 12:12 lighting regimen and persist if
      the animals are kept under a regimen of LD 8:16 or LD 16:8 for 3-4 weeks prior to
      sacrifice.

PMID- 9262872
TI  - 24 h rhythm of the ventricular fibrillation threshold during normal and
      hypoventilation in female Wistar rats.
AB  - A 24 h rhythm of the ventricular fibrillation threshold (VFT) was investigated in
      female Wistar rats under conditions of normal ventilation (NV) (17 animals) and
      hypoventilation (HV) (10 animals). The animals were adapted to a daily 12:12 h
      light-dark cycle with the dark period from 18:00 to 06:00 under constant
      temperature conditions. The experiments were performed in pentobarbital
      anesthesia (40 mg/kg ip, open chest experiments) during the whole year, and the
      obtained results were averaged independently of the seasons. During NV, the VFT
      in female rats showed a significant 24 h rhythm (p < 0.01) with the mesor 2.59 +/
      0.53 mA, amplitude 0.33 +/- 0.11 mA, and acrophase -338 degrees (at 22:53 h) and
      the confidence intervals from -288 degrees to -7 degrees (from 19:12 to 00:28 h)
      using the population mean cosinor test. The maximal values of the VFT were
      measured in the active phase between 24:00 and 03:00 h. During HV, the
      rhythmicity of the VFT showed a more pronounced biphasic character with a smaller
      peak between 15:00 h and 18:00 h hours and a higher peak between 24:00 h and
      03:00 h of the daily regime. Hypoventilation significantly decreased the VFT (p <
      0.001) at each interval of the measurement. It is concluded that the electrical
      stability of the heart measured by the VFT shows a significant 24 h rhythm in
      female Wistar rats and that HV decreased the VFT during the whole 24 h period.

PMID- 9262873
TI  - Morning versus afternoon gymnastic time and diurnal and seasonal changes in
      psychophysiological variables of school children.
AB  - The aims of this study were to document time-related (morning versus afternoon)
      effects of physical activities (gymnastics) on a set of physiological and
      psychological variables in school children, including diurnal changes. For the
      study, 61 boys and 69 girls, 6 to 11 years of age, volunteered. They were
      considered healthy according to routine clinical criteria. They were synchronized
      with diurnal activity from around 07:00 to 21:00 and nocturnal rest, time of year
      being taken into account. Tests were performed at school during 4 weeks of 4.5
      days of school at fixed clock hours: 09:00, 11:00, 14:00, and 16:00. Gym time was
      randomized with regard to week order and season. Four different classes (39 boys
      and 38 girls) were involved in psychophysiological tests, and two different
      classes (22 boys and 31 girls) collected saliva samples for morning free cortisol
      determination. Both t-test and three-factor analysis of variance (ANOVA) were
      used for statistical analyses. Better performances were obtained in June than in
      mid-winter with reference to letter cancellation and random number addition
      tests. As a group phenomenon, morning (09:00 to 10:00) versus afternoon (14:00 to
      15:00) gym was not an influential condition with regard to sleep duration, oral
      temperature, self-rated fatigue and drowsiness, letter cancellation, addition
      tests, or salivary cortisol. However, gym-time-related differences were observed
      in classes of younger subjects (e.g., 6-7 years) with regard to self-rated
      fatigue and the letter cancellation test. Such variability among subgroups
      suggests that interindividual differences are likely to exist in younger children
      with regard to manipulation of environmental factors. In addition, gym itself
      (without gym time consideration) may be an influential factor with regard to
      diurnal patterns of some variables (e.g., the letter cancellation test).

PMID- 9262874
TI  - Changes in endocrine circadian rhythms as markers of physiological and
      pathological brain aging.
AB  - We studied the circadian rhythm of plasma melatonin, growth hormone (GH),
      prolactin (PRL), adrenocorticotropic hormone (ACTH), and cortisol in 52 mentally
      healthy old subjects, 35 old demented patients, and 22 clinically healthy young
      controls. When compared to young controls, the circadian profile of plasma
      melatonin of old subjects, both demented or not, was clearly flattened,
      particularly during the night. The selective impairment of nocturnal melatonin
      secretion was significantly related to both the age and the severity of mental
      impairment (Mini Mental State Examination [MMSE] score). The PRL and GH circadian
      profiles were similar in the three groups during the day, but a significant
      lowering of the values recorded during the night occurred with aging. The
      impairment of the nocturnal secretion was related to the subjects' age and, for
      the GH secretory pattern only, also to the MMSE score. The ACTH circadian profile
      was similar in the three groups studied, even when old subjects exhibited higher
      ACTH levels throughout the 24 h cycle, compared to young controls. Significantly
      higher cortisol values at evening- and nighttime occurred in elderly subjects and
      particularly in the demented group. Both the mean levels and the nadir values of
      plasma cortisol were positively related to age and negatively to MMSE score. In
      order to verify the sensitivity of the hypothalamo-pituitary-adrenal (HPA) axis
      to the steroid feedback, the circadian profile of plasma cortisol was evaluated
      also after dexamethasone (DXM) administration (1 mg at 23:00 h); the sensitivity
      of the HPA axis was significantly impaired in old subjects and particularly in
      the demented ones. These findings suggest that the neuroendocrine alterations
      already present in physiological aging, due to both anatomical damages and
      unbalanced central neurotransmitters, are enhanced in senile dementia.

PMID- 9262875
TI  - Age-related differences of blood pressure profile in essential hypertension.
AB  - The purpose was to assess age-related circadian changes of blood pressure profile
      (BPP) employing a truncated Fourier series with four harmonics (tFs) in patients
      with essential hypertension. The study was performed on 32 patients with
      essential hypertension divided in two groups: (A) 15 patients younger than 55
      years and (B) 17 patients older than 60 years. Systolic blood pressure (SBP) and
      diastolic blood pressure (DBP) were monitored every 20 minutes for 24 h with a
      noninvasive portable device (SpaceLabs 90202). To evaluate the existence of SBP
      and DBP circadian rhythms a one-sample runs-test was performed and the mesor,
      amplitude, and acrophase from the overall curve of each patient were obtained by
      tFs. In both groups, SBP and DBP profiles showed a first peak in the late morning
      and a second peak in the early evening around the same hours. The two peaks in
      the SBP profile were higher and the two peaks in the DBP profile were lower in
      older patients than in younger ones (p < .01, p < .05, p < .3, p < .05). The
      truncated Fourier series with four harmonics evidences different age-related BP
      profiles characterized by two peaks with higher SBP and lower DBP in elderly
      patients. These changes of BPP are in accordance with the reported higher risk of
      cardiovascular events observed around the same hours.

PMID- 9262876
TI  - Computation of time-specified tolerance intervals for hybrid time series with
      nonequidistant sampling, illustrated for plasma growth hormone.
AB  - The ideal reference interval for a variable of clinical interest would be
      specific for all deterministic factors affecting that variable, including the
      time of sampling in relation to biological rhythms. In particular, growth hormone
      is characterized in children by circadian and ultradian variability, with high
      peaks of secretion occurring mainly during sleep. For clinical applications, the
      use of tolerance intervals has been recommended, and they should substitute,
      whenever possible, for prediction limits. In the case of hybrid data (time series
      of data collected from a group of subjects), such a tolerance interval could be
      very difficult to determine following a parametric approach similar to the
      procedure used for the computation of prediction intervals, especially when
      consideration of both within-subjects and among-subjects variances is wanted.
      Accordingly, we have developed a nonparametric method for the computation of such
      tolerance intervals. Because the method is based on bootstrap techniques, it does
      not require the assumption of normality or symmetry in the data and is also more
      appropriate when dealing with small samples. The method was used to establish
      time-qualified reference limits for a series of growth hormone sampled around the
      clock in groups of prepubertal children differentiated according to stature. The
      use of these tolerance intervals may eliminate many false-positive and false
      negative diagnoses that might be obtained when relying on time-unspecified single
      samples. The provision of such tolerance limits introduces time-specification and
      time-structure evaluation into prevention, diagnosis, and treatment of growth
      disorders.

PMID- 9262877
TI  - Crab clocks rewound.
AB  - In response to my advocacy of a circatidal/circadian model to explain behavioral
      rhythms in Carcinus (1), Palmer (2) raises questions concerning my initial
      premise, the nature of one of my model parameters, and the form of data analysis
      that I used. These questions are responded to and it is restated that the
      circatidal/circadian model of clock control adequately explains characteristics
      of free-running behavioral rhythms in Carcinus and probably in some other coastal
      animals, purported to be explained only by the recently formulated circalunidian
      hypothesis (3).

PMID- 9262878
TI  - Dueling hypotheses: circatidal versus circalunidian battle basics--second
      engagement.

PMID- 9262879
TI  - Crab clocks sent for recalibration.

PMID- 9262880
TI  - Environmental conditions during the 1996 Olympic Games: a brief follow-up report.

PMID- 9262881
TI  - Head, neck, and facial injuries in ice hockey: the effect of protective
      equipment.
AB  - OBJECTIVES: To determine the factors and behaviors associated with facial, head,
      and/or neck injuries to those engaged in ice hockey; the use of protective
      equipment was also examined. DESIGN: Prospective case series. SETTING: Emergency
      Department of Sudbury General Hospital. PATIENTS: All patients presenting to the
      emergency department with a head, neck, or facial injury while playing hockey
      between the months of October and March 1993-94 and 1994-95 were included in the
      study. Physicians completed data forms on each patient. Information was validated
      by review of the emergency-room records; further information was obtained by
      telephone. RESULTS: A total of 226 patients were identified with ice-hockey
      related head, neck, or facial injuries. Most injuries involved males (99%), and
      the mean age of patients was 23.9 (range, 4-63). Injuries occurred most
      frequently to the face [192 (85%)]. Many of the injuries were minor, with a mean
      injury severity score of 1.5 (range, 1-25). However, three patients (1%) required
      hospital admission, and one teenager suffered a serious spinal fracture.
      Protective facial hockey equipment use was low in our sample, except among
      younger injured players. Most of the facial injuries occurred in mature athletes
      playing recreational hockey. Full facial protection reduced the chance of upper
      facial injury (p = 0.0001), but the risk of such injury while wearing a half
      visor was the same as while wearing no facial protection at all (p > 0.05). From
      the current study, we estimate that these hockey injuries result in approximately
      2.7-3.0 million dollars of direct acute-care medical expenditure per year in
      emergency departments throughout Ontario. CONCLUSIONS: Head, neck, and facial
      injuries suffered during ice hockey participation are common problems presented
      to emergency departments. Moreover, serious injuries can occur while playing this
      sport. Most injuries appear to be preventable, and facial protection appears to
      be less frequently used, especially by older men, than is currently recommended.
      Prevention strategies are discussed.

PMID- 9262882
TI  - Do pseudoephedrine or phenylpropanolamine improve maximum oxygen uptake and time
      to exhaustion?
AB  - OBJECTIVE: To study the effects of over-the-counter dosages of the pure alpha 1
      agonists pseudoephedrine (PSE) and phenylpropanolamine (PPA) on selected
      parameters of exercise performance, and to establish a range of corresponding
      drug levels in the urine of the athletes who use these drugs. DESIGN: Placebo
      controlled, randomized, double-blinded, multiple-dose trial. SETTING: The
      National Institute of Fitness and Sport, the Department of Family Medicine,
      Indiana University, and the Sports Medicine Lab, Department of Pathology, Indiana
      University, Indianapolis, Indiana. PARTICIPANTS: A convenience sample of 20 male
      cyclists, aged 18-35, from the local cycling community. Inclusion criteria
      required cycling at least 50 miles a week, no chronic medical problems, and not
      taking any medications. Subjects were recruited by local ads and word of mouth.
      INTERVENTION: Patients were randomized to one of two groups of 10 subjects. Each
      subject in both groups performed three separate bicycle ergometer tests after
      ingestion of varying dosages of alpha 1-agonists. One group performed tests after
      receiving placebo, 0.33 mg/kg PPA, and 0.66 mg/kg PPA, whereas the other group
      received placebo, 1 mg/kg PSE, and 2 mg/kg PSE. A minimum 1-week washout period
      was required between tests. Urine for drug testing was collected 1 h before,
      immediately afterward, and the next morning after testing. Drug testing was
      performed by gas GC/MCD at a facility approved by the International Olympic
      Committee. MAIN OUTCOME MEASURES: Maximum oxygen uptake (VO2max), time to
      exhaustion, urine drug levels of PSE and PPA, peak blood pressures (BPs), peak
      pulse, and Borg scale (rating of perceived exertion or RPE). MAIN RESULTS: In the
      PPA group, the 0.33-mg/kg dose resulted in insignificant changes in peak systolic
      BP (+5.4 mm Hg, p = 0.260), peak diastolic BP (-1.6 mm Hg, p = 0.622), peak pulse
      (-2.2 beats/min, p = 0.12), peak Borg (RPE = -0.10 (p = 0.823), time to
      exhaustion (-16.9 s, p = 0.287), and VO2max (+0.50 ml/kg/min, p = 0.71). No
      significant change was noted in any study variable at the 0.66-mg/kg PPA dose,
      and some effects were dissimilar to the lower PPA dose effects. Peak systolic BP
      increased 2.8 mm Hg (p = 0.617), diastolic BP decreased 1.6 mm Hg (p = 0.634),
      peak pulse increased 1.4 beats/min (p = 0.504), peak Borg RPE decreased 0.80 (p =
      0.210), time to exhaustion decreased 2.6 s (p = 0.861), and VO2max decreased 2.92
      ml/kg/min (p = 0.14). In the 1-mg/kg PSE group, there was a significant increase
      in peak systolic BP (+10.6 mm Hg, p = 0.029). No significant changes occurred in
      peak diastolic BP (+2.4 mm Hg, p = 0.333), peak pulse (+2.2 beats/min, p =
      0.306), peak RPE (+0.2, p = 0.62), time to exhaustion (+21.4 s, p = 0.289), and
      VO2max (+2.29 ml/kg/min, p = 0.31). In the 2-mg/kg PSE dose trial, there were
      insignificant changes in peak systolic BP of +2.4 mm Hg (p = 0.559), +3.8 mm Hg
      in peak diastolic BP (p = 0.106), +1.6 beats/min in peak pulse (p = 0.586), -0.1
      in peak Borg RPE scales (p = 0.76), -10.4 s in time to exhaustion (p = 0.41), and
      +1.79 ml/kg/min in VO2max (p = 0.43). Urine drug levels in those subjects
      receiving 1 mg/kg PSE ranged from 7-55 micrograms/ml before performance and 30
      128 micrograms/ ml after performance to 7-35 micrograms/ml the next morning.
      Levels in those receiving 2 mg/kg ranged from 5-160 micrograms/ml before
      performance and 44-200 micrograms/ml after performance to 8-44 micrograms/ ml the
      next day. In the PPA 0.33-mg/kg dose trials, the levels ranged 1-36 micrograms/ml
      before performance and 9-50 micrograms/ml after performance to < 1-14
      micrograms/ml the next morning. In the PPA 0.66-mg/kg dose trials, the levels
      were 4-52 micrograms/ml before performance, 8-80 micrograms/ml after performance,
      and 6-74 micrograms/ml the next day. CONCLUSIONS: We found no significant
      differences between trials in maximum oxygen uptake (VO2max), peak or progression
      of Borg Scale (RPE), maximum systolic and diastolic BPs, peak pulse, or t

PMID- 9262883
TI  - Hip and ankle range of motion in elite classical ballet dancers and controls.
AB  - OBJECTIVE: To report range of motion at the hip and ankle in male and female
      ballet dancers compared with controls. DESIGN: Cross-sectional cohort study with
      convenience control sample. SETTING: National classical ballet school in
      Australia. PARTICIPANTS: Thirty-three female and 30 male full-time ballet
      students of mean (SD) age 16.9 (0.8) and 18.0 (1.4) years, respectively. Controls
      were 31 female and 16 male nondancing, normally active university students of
      average ages 18.8 +/- 0.6 and 18.8 +/- 0.9 years, respectively. MAIN OUTCOME
      MEASURES: Degrees of range of motion of left and right sides for the following
      four movements: standing plie in parallel-passive ankle dorsiflexion (DF),
      standing turnout in the balletic first position-lower limb external rotation
      (LLER), supine hip external rotation (ER), supine hip internal rotation (IR). Two
      additional ranges of motion were calculated. External rotation below the hip
      joint (BHER) was derived by subtracting hip ER from LLER, and total supine hip
      rotation (Hip IR + ER) was derived by summing hip ER and hip IR. MAIN RESULTS: On
      both left and right sides, dancers had greater LLER (p < 0.0001) and hip ER (p <
      0.0001) but lesser hip IR than the controls (p < 0.0001). Female but not male
      dancers had greater total supine hip rotation (hip ER+IR) than controls (p <
      0.05). There was no difference in either BHER or ankle DF between dancers and
      controls. Within dancers, females had greater range in both left and right hip
      IR, LLER, and hip IR + ER. There was no difference in hip ER. Regression analysis
      revealed that LLER related to hip ER in both males and females. CONCLUSIONS:
      Elite classical dance students had greater hip external rotation (both ER and
      LLER) and less hip internal rotation than controls but similar BHER and ankle DF.
      Since ER below the hip joint and ankle DF do not differ between dancers and
      controls, despite repeated training of these movements in ballet, there may be
      anatomical (bony/ligamentous) limitations to these movements.

PMID- 9262884
TI  - Hyponatremia and weight changes in an ultradistance triathlon.
AB  - OBJECTIVE: To describe the weight changes and the incidence of hyponatremia
      during an ultradistance triathlon in the athletes who attend medical care after
      the race. DESIGN: Descriptive research. SETTING: The 1996 New Zealand Ironman
      Triathlon in which each athlete swam 3.8 km, cycled 180 km, and ran 42 km.
      PARTICIPANTS: Ninety-five athletes attending for medical care after the race were
      studied. One hundred sixty-nine athletes who did not attend for medical care were
      also weighed before and after the race. MAIN OUTCOME MEASURES: Weights were
      measured at race registration and on finishing the race. Whole-blood sodium
      concentration was measured in those athletes with clinical evidence of fluid or
      electrolyte disturbances. RESULTS: Weights were significantly decreased at the
      end of the race in the athletes seeking medical care (n = 48, mean % delta wt = 
      2.5%, p < 0.001) and also in the athletes who did not seek medical care (n = 169,
      mean % delta wt = -2.9%, p < 0.001). Seventeen percent of race starters sought
      medical attention. Dehydration accounted for 26% of primary diagnoses and
      hyponatremia for 9%. One athlete with hyponatremia (Na 130 mEq/L) is described
      who drank 16 L over the course of the race, with a weight gain of 2.5 kg. This is
      consistent with the hypothesis of fluid overload as the cause of his
      hyponatremia. Hyponatremia accounted for four of five admissions to the hospital
      after the race. An inverse relationship between postrace sodium concentrations
      and percentage change in body weight was observed (r = -0.63). CONCLUSIONS:
      Hyponatremia is an important risk to the health of athletes competing in an
      ultradistance triathlon, with fluid overload the likely aetiology.

PMID- 9262885
TI  - Influence of exercise-induced plasma volume changes on the interpretation of
      biochemical data following high-intensity exercise.
AB  - OBJECTIVE: To assess the effects that exercise-induced plasma volume changes
      (PVCs) have on the interpretation of biochemical and hormonal parameters in the
      blood of athletes after high-intensity exercise. It was hypothesized that two
      unrelated high-intensity exercise protocols, performed by two separate subject
      groups each using different exercise modes, would result in similar percentage
      changes in plasma volume (% delta PV). It was further hypothesized that the %
      delta PV, measured in both protocols, would comparably influence the
      interpretation of biochemical variables measured following exercise. DESIGN: An
      experimental before-after trial on volunteers was performed. Two different
      exercise modes employing two different high-intensity acute exercise protocols
      were investigated. Eight male swimmers performed an interval training session
      (ITS) consisting of 15 x 100-m freestyle efforts at 95% of their maximal exercise
      intensity, and eight male runners performed a multistage discontinuous treadmill
      test (MSD) to volitional exhaustion. SETTING: The Human Performance Laboratory at
      the Department of Human Movement at the University of Western Australia. MAIN
      OUTCOME MEASURES: Blood samples obtained before, immediately after, and 30, 60,
      and 120 min during recovery were analyzed for plasma volume changes, urea, uric
      acid, creatinine, albumin, calcium, iron, transferrin, testosterone, cortisol,
      and sex hormone-binding globulin (SHBG). MAIN RESULTS: The ITS and MSD protocols
      produced similar and significant alterations (p < 0.01) in plasma volume. Both
      protocols also elicited significant fluctuations (p < 0.01) in the concentration
      of most of the parameters measured (excluding iron). When albumin, transferrin,
      testosterone, and SHBG values were adjusted for the significant % delta PV, their
      concentrations did not change over the experimental period, suggesting that the
      changes in measured concentration of these parameters may be, in part, due to
      changes in plasma volume. However, urea, uric acid, creatinine, calcium, and
      cortisol, when corrected for % delta PVC, still demonstrated significant changes
      (p < 0.01). CONCLUSIONS: It is recommended, when sampling biochemical and
      hormonal parameters in blood following an acute bout of exercise, that
      corrections for PVCs should be conducted. Apparent changes in blood solutes may
      reflect PVCs. PVCs should be taken into consideration when interpreting results
      regardless of exercise protocol and exercise mode performed.

PMID- 9262886
TI  - Safety in Canadian junior ice hockey: the association between ice surface size
      and injuries and aggressive penalties in the Ontario Hockey League.
AB  - OBJECTIVE: To investigate the associations between ice surface size and injuries
      and aggressive penalties in Canadian junior hockey. DESIGN: Injury (all injuries
      and neurotraumas) and penalty data (aggressive and nonaggressive) were
      categorized into the ice surface size on which they occurred: larger than
      standard (LTS), standard (S), and smaller than standard (STS). PARTICIPANTS:
      There were 328 injury records and 538 penalty records collected for all 16 teams
      in the Ontario Hockey League (OHL) during the 1993-94 season. The OHL is a junior
      A league comprised of amateur players aged approximately 16-20 years. MAIN
      OUTCOME MEASURE: In the absence of any evidence, the null hypotheses of no
      association between injuries and ice surface size and penalties and ice surface
      size were tested. RESULTS: The rates of injury per game were inversely related to
      ice surface sizes (95% confidence intervals: LTS, 0.33 +/- 0.20; S: 0.58 +/-
      0.08; and STS, 0.76 +/- 0.06). The associations for all of the paired comparisons
      of these rates with ice surface size were statistically significant (p < 0.01).
      Neurotraumas per game and aggressive penalty rates showed no significant
      relationship with ice surface size (p < 0.05). CONCLUSIONS: It was concluded that
      ice surface size is a risk factor to consider in assessing overall injury rate.
      The larger the ice surface is, the lower is the rate of injury. It appears that
      the medical community was correct in suspecting ice surface size as a factor in
      creating a safer environment for ice hockey players. Penalty data do not appear
      to be important factors in relation to ice surface size.

PMID- 9262887
TI  - Serial sevens: not the most effective test of mental status in high school
      athletes.
AB  - OBJECTIVE: To evaluate the ability of uninjured high school athletes to pass
      three mental status tests that are commonly used on the sidelines for the
      evaluation of concussions: the serial sevens test, the serial threes test, and
      recitation of months of year in reverse order (MOYR). PARTICIPANTS: High school
      student athletes in grades 9, 10, 11, and 12 having sports preparticipation
      physical examinations. The initial study tested 522 consecutive athletes. The
      follow-up study tested 109 consecutive athletes. INTERVENTION: The athletes of
      the initial group were asked to perform a serial sevens test, followed by a
      serial threes test, and finally to recite the MOYR. The second group was asked to
      perform the same tests in a random order. MAIN OUTCOME MEASURES: Participants
      were given 1-min time limits for each test, with passing defined as either 7
      consecutive correct iterations or 11 correct with one mistake. RESULTS: For the
      initial group, 51.3% successfully performed serial sevens, 78.7% successfully
      performed serial threes, and 89.5% successfully recited the MOYR. For the second
      group, 52.7% successfully performed serial sevens, 78.1% successfully performed
      serial threes, and 88.9% successfully recited the MOYR. The pass rates were
      significantly different for both groups. The pass rates were similar for both
      sexes, all grade levels, and all sports in both test groups. Participants, both
      overall and in all subgroups, failed serial sevens more often than serial threes
      and MOYR (p < 0.001 for the initial group; p < 0.0001 for the second group). They
      failed serial threes more often than MOYR (p < 0.001 for the initial group; p <
      0.01 for the second group). CONCLUSIONS: The percentage of uninjured high school
      athletes successfully completing serial sevens is too low to make the test useful
      for evaluation of concussion; the test lacks specificity. The percentage of
      athletes passing the MOYR was greatest, perhaps making this a better sideline
      test than the traditional serial sevens test. However, testing needs to be done
      in injured athletes before clinical application can be recommended.

PMID- 9262888
TI  - Patellar tendon ultrasonography and jumper's knee in female basketball players: a
      longitudinal study.
AB  - OBJECTIVE: To compare patellar tendon sonographic findings at baseline and at
      follow-up in active female basketball players with and without symptoms of
      jumper's knee. We hypothesized that baseline sonographic morphology would not
      reliably predict prognosis and, in particular, that it would not predict the need
      for surgery. DESIGN: Prospective longitudinal study with 12-month minimum follow
      up. SETTING: Institutional elite athlete study group in Australia (Victorian
      Institute of Sport Tendon Study Group). PATIENTS AND PARTICIPANTS: A total of 15
      female elite basketball players with 23 sonographically abnormal tendons and 15
      matched control basketball players with 23 sonographically normal tendons. MAIN
      OUTCOME MEASURES: Sonographic patellar tendon appearance and clinical assessment
      of symptoms of jumper's knee at baseline and follow-up. Dimensions of abnormal
      regions were measured. RESULTS: At baseline, the 23 subject tendons contained
      sonographic hypoechoic regions (six currently symptomatic, eight previously
      symptomatic only, and nine never symptomatic). At follow-up, the hypoechoic areas
      in seven tendons had resolved (and caused no symptoms), the hypoechoic areas in
      11 tendons had remained essentially the same size (five were symptomatic), and
      the hypoechoic areas in five tendons had expanded (three symptomatic). At
      baseline, there were no differences between the mean +/- SD cross-sectional areas
      of the abnormalities in the tendons that subsequently resolved (15.9 +/- 10.1
      mm2) and those that remained unchanged (39.3 +/- 25.8) or expanded (25.3 +/-
      12.5). The presence of a baseline sonographic abnormality predicted symptoms of
      jumper's knee at follow-up (p < 0.05), but the presence of symptoms of jumper's
      knee at baseline also predicted symptoms at follow-up (p < 0.05). No subject or
      control missed any games or underwent surgical treatment. CONCLUSIONS: Patellar
      tendon sonographic hypoechoic areas can resolve, remain unchanged, or expand in
      active sports-women without predicting symptoms of jumper's knee. Thus, symptoms
      were not directly related to sonographic tendon morphology. Sonographic
      hypoechoic regions ought not to constitute per se an indication for surgery.

PMID- 9262889
TI  - Operative versus nonoperative treatment of acute Achilles tendon ruptures: a
      quantitative review.
AB  - OBJECTIVE: To determine the optimal treatment of acute Achilles tendon ruptures.
      DATA SOURCES: A comprehensive search for all of the English articles published
      between 1959 and 1997. STUDY SELECTION: All of the articles were reviewed
      independently by at least three of the four authors to decide on eligibility
      based on predetermined criteria. Disagreements were discussed and then settled,
      if necessary, by a majority vote. DATA EXTRACTION: Eligible studies were reviewed
      independently, and data were extracted by using standardized coding forms.
      Inconsistencies in data extraction were settled by discussion and majority vote.
      The main outcomes extracted were strength, time to return to work, frequency of
      return to sports, rerupture rate, and complications. Complications were divided
      into major, moderate, and minor categories. DATA SYNTHESIS: The overall rerupture
      rate was 2.8% for operatively treated and 11.7% for nonoperatively treated
      patients (p < 0.001). The rate of minor and moderate complications in operatively
      treated patients was 20 times that of nonoperatively treated patients. The
      difference in rates for major complications was not statistically significant.
      CONCLUSIONS: Although operative treatment provides a reduced rerupture rate
      compared with nonoperative treatment, the minor and moderate complication rate of
      operative treatment is 20 times greater. Treatment should be individualized to
      the concerns and health of the patient. Future clinical trials are necessary to
      determine the optimal method of both operative and conservative treatment.

PMID- 9262890
TI  - Cryotherapy-induced common peroneal nerve palsy.
AB  - PURPOSE: To report an uncommon complication of distal hamstring icing,
      cryotherapy-induced common peroneal nerve palsy. CASE SUMMARY: A 22-year-old
      football player applied ice to his distal hamstring for 20 min because of
      soreness. This application of ice resulted in foot drop and sensory changes in
      the anterior lower leg and dorsum of the foot. Over the next year, full clinical
      neurologic function returned. DISCUSSION: Previously reported cases of
      cryotherapy-induced common peroneal nerve palsy involved lateral knee or
      circumferential thigh icing with nerve injury at the fibular neck. This case
      involved distal hamstring icing, and nerve injury occurred more proximally.
      RELEVANCE: This case demonstrates that caution should be used even when using a
      modality as common as ice. Ice exposure should be limited in patients with low
      body fat or in areas where a nerve is not well protected by subcutaneous tissue.

PMID- 9262891
TI  - Obturator nerve entrapment.
AB  - PURPOSE: To describe a case of obturator nerve entrapment, a previously
      unreported cause of chronic groin pain in athletes. CASE SUMMARY: A 23-year-old
      man, an elite Australian rules footballer, presented with a 2-year history of
      groin pain. Conservative treatment was unsuccessful. Examination postexercise
      revealed adductor weakness and medial thigh paraesthesia. Diagnosis of obturator
      nerve entrapment was confirmed by EMG and nerve block. Surgical neurolysis was
      performed. The patient returned to sport and has remained symptom free.
      DISCUSSION: Although intrapelvic obturator nerve entrapment has been reported
      following surgical trauma, no cases of sport-related entrapment have been
      described. RELEVANCE: Obturator nerve entrapment should be considered as a
      potential cause of chronic groin pain in athletes.

PMID- 9262892
TI  - Fifth metacarpal stress fracture in a female softball pitcher.
AB  - PURPOSE: This article describes a previously unreported fifth metacarpal stress
      fracture. CASE SUMMARY: A female softball pitcher presented with gradual
      development of dorsal pain in her pitching hand. A radioisotope scan showed
      increased uptake in the fifth metacarpal. This supported a clinical diagnosis of
      a stress fracture, and the patient was treated with a period of relative rest. At
      6 weeks, the patient was able to return to pitching with technique modification.
      DISCUSSION: Seven cases of metacarpal stress fractures have been reported, yet
      none involved the fifth metacarpal. The causes of a fifth metacarpal stress
      fracture differ from those of other metacarpals and may be a combination of
      extrinsic forces from the ball and intrinsic forces from muscle pull. Although
      treatment involves the standard rest period, technique must be assessed and
      appropriately adjusted. RELEVANCE: Metacarpal stress fractures should be
      considered in athletes with persistent hand pain where repetitive grip function
      is used.

PMID- 9262893
TI  - Sacral stress fractures in long-distance runners.

PMID- 9262894
TI  - Applying functional status measures to individual patients.

PMID- 9262895
TI  - Tc-99m pertechnetate thyroid images in hyperthyroidism. Size, distribution, and
      presence of a pyramidal lobe.
AB  - One hundred consecutive thyroid images obtained by use of Tc-99m pertechnetate,
      in authenticated cases of hyperthyroidism, were reviewed. Calibrated images
      showed that only 42 of the 200 thyroid lobes (21%) were greater than 5 cm in
      length. The enlarged lobes occurred in 29 patients. Of these, only 4 had a
      multinodular appearance (and 7 patients with smaller lobes also had multinodular
      glands). Neither thyromegaly (by length) nor multinodular appearance are common
      features of hyperthyroidism in this area. There were 12 instances of pyramidal
      lobes in the hyperthyroid men (12 of 26 = 46%) and 24 cases in women (24 of 74 =
      32%). The site of origin of the pyramidal lobe was from the left in 17, from
      right in 16, and from the midline in 3 cases. During the period of review of all
      thyroid images, only one other case of a pyramidal lobe was found (a case of
      multinodular goiter).

PMID- 9262896
TI  - Diagnosis of postoperative urinary ascites using renal scintigraphy.
AB  - Nuclear medicine biliary studies have been routinely used to identify bile leaks
      that occur after laparoscopic cholecystecomy. The use of a Tc-99m
      mercaptoacetyltriglycine (MAG3) renal scan to diagnose a case of urinary leakage
      that occurred after a laparoscopic-assisted colectomy is shown in this report.
      Laparoscopic surgery is widely used in place of conventional laparotomy to
      minimize recovery time and discomfort after surgery. The complication rate for
      laparoscopic colectomy has been reported as approximately 6% to 10%. In
      particular, ureteral leak has been reported in 2% of procedures. Ascites of
      unknown origin can become a diagnostic dilemma. We present a case of
      postoperative ascites of unknown origin that was successfully diagnosed as
      urinary leakage using renal scintigraphy.

PMID- 9262897
TI  - Radionuclide angiography and ventilation/perfusion studies in two patients with
      systemic arterial supply to the basal segment of the left lung.
AB  - The findings of radionuclide studies in two adult men with systemic arterial
      supply to the basal segment of the left lung without sequestration are reported.
      Radionuclide angiography with Tc-99m human serum albumin-diethylenetriamine
      showed that the lung was perfused by the systemic circulation rather than by the
      pulmonary artery. Ventilation and perfusion scans with Xe-133 and Tc-99m MAA
      showed a V/Q mismatch in this area, suggesting the presence of normal bronchial
      communication without a pulmonary arterial supply. These results also suggest the
      presence of a left-to-left shunt in the well-ventilated lung in this area. MRI
      and conventional angiography showed an aberrant artery arising from the
      descending thoracic aorta, supplying the basal segment of the left lung without a
      pulmonary artery. In both patients, left lower lobectomy showed normal
      alveobronchial structures without sequestration. Radionuclide angiography and
      ventilation/perfusion imaging appear to be reliable noninvasive methods for
      diagnosing this rare anomaly with a left-to-left shunt.

PMID- 9262898
TI  - Scintigraphy of lower extremity cadaveric bone allografts in osteosarcoma
      patients.
AB  - PURPOSE: To describe scintigraphic characteristics of bone allografts used in
      limb salvage reconstruction after resection of lower extremity osteosarcoma.
      MATERIALS AND METHODS: The authors reviewed 85 skeletal scintigrams of 20
      pediatric patients followed up for 0.5-5.7 years after resection of lower
      extremity osteosarcoma and allograft reconstruction. Uptake in the allograft and
      adjacent host tissues was assessed visually. RESULTS: Lack of tracer uptake in
      the allografts was seen in 99% of the studies and a faint rim of tracer
      localization outlining the allograft's periphery was seen in 95% of the studies.
      Increased uptake was noted at the allograft-host bone junction in 78% of the
      studies. Uptake was increased in the joint surfaces of native bones articulating
      with allografts (97% of studies), including the patella (93% of studies) when the
      knee was involved. These findings were stabilized as time passed. CONCLUSION:
      Cadaveric bone allografts have a characteristic scintigraphic appearance in this
      selected patient group that reflects the physiology of their incorporation
      process.

PMID- 9262900
TI  - Focal hyperemia on RBC blood-flow imaging. A scintigraphic marker of
      arterioportal venous shunting in hepatic cavernous hemangiomas?
AB  - PURPOSE: To investigate the significance of increased perfusion associated with
      some hepatic hemangiomata during radionuclide blood volume imaging. METHODS:
      Immediate dynamic planar projections and delayed SPECT imaging of a hepatic
      lesion were obtained after the administration of Tc-99m-labeled RBC.
      Scintigraphic data were compared with X-ray CT, contrast angiography and
      postresection histopathology. RESULTS: A surgically proven, cavernous hemangioma
      with typical findings on delayed radionuclide blood-pool imaging showed markedly
      increased perfusion by scintigraphy. This correlated with arterioportal venous
      shunting (AVPS) on contrast angiography. CONCLUSION: Increased perfusion on
      radionuclide blood-volume imaging of hepatic hemangiomata may be a scintigraphic
      marker of AVPS. This may serve to identify patients with increased risk for
      spontaneous rupture or may identify them for the development of portal
      hypertension.

PMID- 9262899
TI  - The usefulness of Tc-99m HMPAO labeled WBC SPECT in eosinophilic gastroenteritis.
AB  - Tc-99m HMPAO labeled WBC SPECT was performed in 5 patients with eosinophilic
      gastroenteritis before and after successful medical therapy. The imaging findings
      were graded according to the following imaging scheme; grade 0, no uptake; grade
      1, uptake < bone marrow; grade 2, uptake < liver; grade 3, uptake > liver. In no
      patient was the diagnosis made radiologically or with colonoscopy. The sites of
      involvement were identified with Tc-99m HMPAO WBC imaging in all patients before
      treatment and the radionuclide imaging studies were all negative after therapy.

PMID- 9262901
TI  - Diagnosis of orbital cavernous hemangioma with Tc-99m RBC SPECT.
AB  - The authors report two cases of orbital cavernous hemangioma diagnosed by Tc-99m
      RBC SPECT. Tc-99m RBC SPECT showed a typical scintigraphic pattern commonly seen
      in hepatic hemangioma in which there is intense focally increased uptake on
      delayed SPECT images. Tc-99m RBC SPECT in orbital cavernous hemangioma may be as
      useful a diagnostic modality as in hepatic hemangioma.

PMID- 9262902
TI  - Transient liver accumulation of Tc-99m phytate in hepatocellular carcinoma after
      percutaneous ethanol injection.
AB  - PURPOSE: We report that colloid liver scanning gave early evidence of the return
      to normal of Kupffer cell functions after ethanol injections into the liver.
      PATIENT AND METHODS: A 71-year-old man with hepatocellular carcinoma received
      percutaneous ethanol injections twice of 15 mL of ethanol, 1 week apart. RESULTS:
      Abdominal CT after the second injection showed an irregularly shaped low-density
      area in the left side of the tumor, extending outside the tumor. Liver imaging
      with To-99m phytate 10 days later showed increased activity at the corresponding
      site. Thirty days after the second injection, liver imaging did not show high
      activity. CONCLUSIONS: Ethanol that leaked into the normal part of the liver
      probably temporarily activated Kupffer cell function.

PMID- 9262903
TI  - Tc-99m sestamibi and Tc-99m HMDP uptake in a malignant phyllodes tumor of the
      breast.

PMID- 9262904
TI  - Tc-99m MAG3 demonstration of polycystic kidneys in tuberous sclerosis.

PMID- 9262905
TI  - FDG uptake in gestational sac.

PMID- 9262906
TI  - Incidental finding of a urinoma on bone scintigraphy.

PMID- 9262907
TI  - Pulmonary atresia with intact septum. Findings on exercise stress sestamibi scan.

PMID- 9262908
TI  - Reversal of Ga-67 'bone scan' with vitamin B12 therapy in a patient with
      pernicious anemia.

PMID- 9262909
TI  - Bilateral and symmetric accumulation of Tc-99m MDP in breast prostheses.

PMID- 9262910
TI  - Discrepancy between 24-hour I-131 and 30-minute Tc-99m tetrofosmin thyroid
      imaging in thyroiditis.

PMID- 9262911
TI  - Pancreatitis secondary to endoscopic retrograde cholangiopancreatography on a
      whole-body Ga-67 scan.

PMID- 9262912
TI  - Delayed epiphyseal closure attributable to androgen deficiency.

PMID- 9262914
TI  - Hydrocele mimicking testicular torsion on radionuclide and ultrasound studies.

PMID- 9262913
TI  - Tc-99m HMPAO uptake in renal cell carcinoma metastases.

PMID- 9262915
TI  - I-123 uptake in the chest wall after needle biopsy of a pulmonary nodule. A cause
      for false-positive I-123 uptake.

PMID- 9262916
TI  - Neurofibromatosis type I shown by Tc-99m (V) DMSA.

PMID- 9262917
TI  - Chilaiditi's syndrome. Incidental findings on Ga-67 scintigraphy.

PMID- 9262919
TI  - Immunodeficiency in the adult patient.

PMID- 9262918
TI  - New contraceptive options for adolescents.

PMID- 9262920
TI  - Natural origins of gynecologic treatment.

PMID- 9262921
TI  - Chronic cough.

PMID- 9262922
TI  - Management of congestive heart failure in primary care settings.

PMID- 9262923
TI  - Hair & nail problems.

PMID- 9262924
TI  - Hepatitis A-G prevention, diagnosis, & therapy.

PMID- 9262925
TI  - Donepezil (Aricept) therapy for Alzheimer's disease.

PMID- 9262926
TI  - Breastfeeding definitions.

PMID- 9262927
TI  - Multicenter study of the Lactational Amenorrhea Method (LAM): I. Efficacy,
      duration, and implications for clinical application.
AB  - A multicenter study of the Lactational Amenorrhea Method (LAM) was carried out to
      test the acceptability and efficacy of the method. Additionally, the data are
      used to test new constructs for improvement of method criteria. A protocol was
      designed at the Institute for Reproductive Health (IRH), Department of Obstetrics
      and Gynecology, Georgetown University Medical Center, a World Health Organization
      (WHO) Collaborating Center, and was reviewed and modified in collaboration with
      the co-sponsors, the World Health Organization and the South to South Cooperation
      for Reproductive Health, and the principal investigators from each site. Data
      were gathered prospectively on LAM acceptors at 11 sites. Data were entered and
      cleaned on-site and further cleaned and analyzed at IRH, using country-level and
      pooled data to produce descriptive statistics and life tables. The 98+% efficacy
      of LAM is confirmed in a wide variety of settings. In addition, the results yield
      insight on the possibility of continued use beyond 6 months. LAM is found to be
      highly effective as an introductory postpartum method when offered in a variety
      of cultures, health care settings, socio-economic strata, and industrial and
      developing country locales. In addition, LAM acceptance complements breastfeeding
      behaviors without ongoing breastfeeding support services. The parameters studied
      yield high efficacy and method continuation. Therefore, the basic tenets of the
      1995 Bellagio consensus on LAM is reconfirmed and it is recommended that LAM be
      reconfirmed and it is recommended that LAM be incorporated into hospital,
      maternity, family planning, maternal and child health, and other primary health
      care settings.

PMID- 9262928
TI  - Multicenter study of the Lactational Amenorrhea Method (LAM): II. Acceptability,
      utility, and policy implications.
AB  - A multicenter study of the Lactational Amenorrhea Method (LAM) was carried out to
      determine acceptability, satisfaction, and utilization in 10 different
      populations, and to confirm the efficacy of the method. Efficacy data are
      presented in a companion paper. A protocol was designed at the Institute for
      Reproductive Health (IRH), Department of Obstetrics and Gynecology, Georgetown
      University Medical Center, and reviewed and modified in collaboration with the co
      sponsors, the World Health Organization, the South-to-South Cooperation for
      Reproductive Health, and the principal investigators from each site. Data were
      gathered prospectively on LAM users at 11 sites. Data were entered and cleaned on
      site, and further cleaned and analyzed at IRH, using country-level and pooled
      data to produce descriptive statistics. The overall satisfaction with LAM was
      83.6%, and continuation with another method of family planning was shown to be
      67.6% at 9 months postpartum, in most cases exceeding previous use of
      contraception prior to use of LAM. Knowledge and understanding of the method at
      discontinuation were high, ranging from 78.4 to 88.6% for the three criteria. LAM
      can be used with a high level of satisfaction and success by women in a variety
      of cultures, health care settings, socio-economic strata, and industrial and
      developing country settings. The results confirm that LAM is acceptable and ready
      for widespread use, and should be included in the range of services available in
      maternal and child health, family planning, and other primary health care
      settings.

PMID- 9262929
TI  - Premature introduction of progestin-only contraceptive methods during lactation.
AB  - Experts on contraceptive technology concur that progestin-only methods can be
      used safely during lactation. However, very few studies exist of the effects on
      lactation of the introduction of progestin-only methods prior to the sixth
      postpartum week. Since progesterone withdrawal is the likely stimulus that
      initiates lactogenesis, it appears necessary for natural progesterone levels to
      decline to baseline before a progestin-only contraceptive is initiated.
      Therefore, the use of such contraceptive methods should be delayed for at least 3
      days after the birth. Non-hormonal methods remain the first choice category of
      contraceptive methods for breastfeeding women, since there is no possibility that
      they will interfere with lactation. Progestin-only methods comprise a viable and
      often desirable next choice category, although the timing of their commencement
      must be determined with care in order to support lactation.

PMID- 9262930
TI  - Modified minilaparotomy technique of interval female sterilization.
AB  - The study of a modified minilaparotomy technique of interval female sterilization
      is reported. The modified minilaparotomy technique of interval female
      sterilization is performed under local anesthesia using the Ramathibodi uterine
      manipulator, bivalve speculum, and a low midline incision. Sixty cases were
      treated with this technique. From the study, it was revealed that the mean age of
      patients +/- SD was 31.2 +/- 5.6 years, the mean body weight +/- SD was 43.3 +/-
      5.1 kg, and the mean height +/- SD was 152.1 +/- 8.2 cm. The mean operating time
      was 24.3 +/- 5.5 min with a range from 15 to 35 min. All patients recovered and
      were allowed home within 2 h after operation. No immediate or late complications
      were observed. It was concluded that this technique is quick, safe, inexpensive,
      and easy to perform as an outpatient procedure.

PMID- 9262931
TI  - Contraceptive use in women with bacterial vaginosis.
AB  - The aim of the study was to investigate if bacterial vaginosis (BV) is associated
      with use of specific contraceptives. Women at family planning and youth clinics
      (n = 956), among whom 131 had BV, were subjects for structured in-depth
      interviews including current and previous contraceptive use. Variables measuring
      sexual risk-taking were ascertained. Current users of contraceptives were
      compared with non-users. Both oral contraceptive (OC) and condom use showed a
      significant protective effect against BV, adjusted for possible confounders (odds
      ratios were 0.4 and 0.3, respectively). Intrauterine device use (IUD) showed no
      association with BV. Women with BV had less often used any contraceptives,
      including condom, at their sexual debut than the women in the comparison group.
      In this study, OC and condom use seemed to exert a protective effect against BV,
      whereas no effect for IUD use was found.

PMID- 9262932
TI  - A multicenter comparative study on the efficacy, safety, and acceptability of the
      contraceptive subdermal implants Norplant and Norplant-II.
AB  - In order to assess efficacy, safety, and acceptability of the contraceptive
      subdermal implants Norplant and Norplant-II in Mexican women, a comparative phase
      III clinical trial was undertaken in eight clinics across the country. The study
      involved 1052 women who were followed-up trimonthly for three years. Cumulative
      pregnancy rates were 0.29% and 0.34% for Norplant and Norplant-II implants,
      respectively. Similar overall cumulative discontinuation rates were observed at
      three years: 50.38% for Norplant capsules, and 50.44% for Norplant-II rods. The
      main method-related reason for termination was endometrial bleeding irregularity
      which led to discontinuation rates of 11.94% and 11.62% for Norplant and Norplant
      II contraceptive systems, respectively. In 15,279 woman-months of experience
      accumulated with Norplant implants and 14,092 with Norplant-II implants, there
      were few adverse events reported. No difference was found between the two groups
      in either difficulty for implants placement and removal or women's discomfort,
      even though the time required for insertion and removal of Norplant capsules was
      longer than for Norplant-II rods. It is concluded that during the first three
      years of use, both implants systems are equally effective, safe, and acceptable.

PMID- 9262933
TI  - Study on antifertility effect of a novel LHRH antagonist in male rats.
AB  - The potential of a novel LHRH antagonist, TX54, to inhibit reproductive function
      in male rats was evaluated. After subcutaneous injection at a dosage of 200
      micrograms/rat, once a week for 2 weeks, all the drug-treated male rats
      maintained mating behavior. But, only one out of seven female rats mated to
      treated males was pregnant with two fetuses. At the end of medication, sperm
      count and motility of caudal epididymal spermatozoa of the treated rats were
      reduced significantly (TX54 vs. control: 11.3 +/- 3.2 x 10(8)/mg epididymal
      plasma, 66.4 +/- 13.4% vs 18.4 +/- 2.4 x 10(8)/mg epididymal plasma, 83.0 +/-
      2.7%). Suppression of serum testosterone by TX54 was not observed 48 h after drug
      injection and at the end of experiment. Morphological examination revealed that
      at the IX stage of seminiferous epithelium cycle, spermiation was impaired in
      TX54-treated rats. Less elongated spermatids were found in the lumen of
      seminiferous tubules of the treated rats. The size of Leydig cells decreased;
      psychosis and apoptosis features occurred.

PMID- 9262934
TI  - Pharmacokinetics of orally administered norethisterone enanthate in rabbit,
      monkey, and women.
AB  - Norethisterone enanthate (NET-En), an established intramuscular long-acting
      contraceptive agent, has previously been shown to be effective in inhibiting
      fertility in two rodent species even 4 days after oral ingestion.
      Pharmacokinetics of NET and NET-En were studied after oral and intramuscular
      doses in two animal species and a few women. The results suggest that the NET-En
      was absorbed within a day in all the species after oral dose. The estimates of
      relative bioavailability ranged from 13 to 51% in rabbits, monkeys, and women.
      The elimination half-life was 5-10 days. The presence of the active component,
      NET, in the circulation over the experimental period of 15 days suggests that NET
      En could be useful as a long-acting oral pill. The suppression of progesterone
      levels during the luteal phase of menstrual cycle in women also supports this
      finding.

PMID- 9262935
TI  - Meta-analysis of erythrocyte Na,K-ATPase activity in bipolar illness.
AB  - Sodium, potassium-activated adenosine triphosphatase (Na,K-ATPase) pump activity
      has been variously reported to be increased, decreased, or unchanged in bipolar
      patients. To explore this association we conducted a meta-analysis of the
      available literature. All papers containing data on erythrocyte Na,K-ATPase
      activity were reviewed independently by both authors. A meta-analysis of these
      data was accomplished by standard procedure. We found a significant mood-state
      related decrease in Na,K-ATPase activity in both manic and bipolar depressed
      patients when compared to euthymic bipolar patients, but not when ill patients
      were compared to normal controls. The overall change can be characterized as
      small to moderate in magnitude.

PMID- 9262936
TI  - Childhood adversity and vulnerability to mood and anxiety disorders.
AB  - Based upon epidemiological surveys, adverse childhood events are proposed to be
      risk factors for adult depressive and anxiety disorders. However, the extent to
      which these events are seen in clinical patient populations is less clear. We
      examined the prevalence of a number of proposed risk factors for depression in
      650 patients with mood and anxiety disorders at the time of presentation for
      treatment in an outpatient subspecialty clinic. Emotional abuse, physical abuse,
      or sexual abuse (childhood adversity) was found in approximately 35% of patients
      with major depression and panic disorder, was more common in women than men, and
      was associated with an earlier onset of symptoms. Childhood adversity was also
      strongly associated with marital discord/divorce, and psychopathology in a
      parent, suggesting family discord predisposes to childhood abuse. Furthermore,
      the association of childhood abuse with parental mental illness suggests that
      genetic and environmental factors are difficult to separate as etiological
      factors in vulnerability.

PMID- 9262937
TI  - Bipolar depression: an underestimated treatment challenge.
AB  - We sought to determine whether depressive and mixed/cycling episodes were as
      responsive to standardized pharmacotherapeutic interventions as were manic
      episodes in bipolar 1 patients. As part of the Maintenance Therapies in Bipolar
      Disorder (MH29618, E. Frank, PI) study, forty-two acutely ill bipolar 1 patients
      who had been randomly assigned to one of two preliminary phase non-pharmacologic
      treatment strategies (interpersonal and social rhythm therapy [IPSRT] or a
      standard medication clinic approach) were treated according to a standardized
      pharmacotherapeutic protocol. Symptom severity was measured weekly with the
      Hamilton Depression Rating Scale and the Bech-Rafaelsen Mania Scale in order to
      assess symptomatic remission. Survival analysis with the proportional hazards
      model was performed on time to remission. Manic patients were significantly more
      likely to achieve clinical remission than the depressed patients (100 vs. 59%)
      and did so significantly more rapidly. The difference in proportion remitting and
      time to remission between the depressed and mixed/cycling groups was not
      statistically significant. No significant effect for non-pharmacologic treatment
      assignment was found. These results point to the need to develop more effective
      treatments for bipolar depression. They also suggest that psychotherapy has a
      limited impact in the acute phase treatment of bipolar episodes.

PMID- 9262938
TI  - Clomipramine augmentation in treatment-resistant depression.
AB  - In depression that is resistant to tricyclic antidepressant (TCA) therapy, the
      substitution of a selective serotonin re-uptake inhibitor (SSRI), clomipramine,
      or a monoamine oxidase (MAO) inhibitor has been recommended. However, adding an
      additional antidepressant medication from a different drug class may produce even
      more rapid efficacy. In this regard, the combination of a MAO inhibitor or a SSRI
      plus a TCA has been shown to be of value in treatment-resistant depression (TRD).
      In this report, we examined the efficacy of clomipramine augmentation in 20
      patients who failed to respond to either a MAO inhibitor or fluoxetine therapy
      for at least a 6-week period, and compared this to a third group given MAO
      inhibitor plus a conventional TCA. Two out of 9 (22%) MAO inhibitor/clomipramine
      patients and 4 out of 11 (36%) fluoxetine/clomipramine patients improved
      (Fisher's Exact test, P = ns), compared to 3 out of 7 (43%) patients taking MAO
      inhibitor/TCA (P = ns). However, the MAO inhibitor/clomipramine group experienced
      significantly more adverse events which necessitated stopping treatment (56%)
      when compared to the fluoxetine/clomipramine (9%) and compared to the MAO
      inhibitor/TCA group (0%) (chi 2 = 8.9, df = 2, P < 0.05). These adverse events
      included several cases of serotonin syndrome of mild to moderate severity. These
      observations indicate that clomipramine augmentation of a failed MAO inhibitor
      trial is of marginal efficacy (compared to augmentation with a conventional TCA)
      and should be employed with extreme caution.

PMID- 9262939
TI  - Prevalence of antithyroid antibodies in mood disorders.
AB  - We examined the prevalence of antimicrosomal and antithyroglobulin antibodies in
      psychiatric inpatients with unipolar depression (N = 218), bipolar disorder manic
      (N = 51), bipolar disorder depressed (N = 19), and bipolar disorder mixed (N =
      26) in comparison with two control groups: psychiatric inpatients with adjustment
      disorder (N = 80) and family medicine outpatients without current psychiatric
      illness (N = 144). A statistical analysis that controlled for age and sex
      revealed the frequency of positive antibody titers not to be increased in
      patients with a diagnosis of unipolar depression (6.9%) or bipolar disorder manic
      (3.9%), when compared with patients with adjustment disorder (2.5%) and non
      psychiatric subjects (6.9%). There was a weak trend toward an increased
      prevalence of antithyroid antibodies in patients with bipolar disorder, mixed
      (19%) or depressed subtype (16%). The excess occurrence of antibodies in patients
      with either mixed or depressed bipolar disorder did not appear to be related to
      lithium exposure, which was similar in all bipolar subgroups. When the
      intervening influences of age and sex are taken into account, unipolar depression
      does not appear to be associated with an excessive rate of antithyroid
      antibodies; however thyroid autoimmunity may be weakly associated with subtypes
      of bipolar disorder in which depressive symptoms are prominent.

PMID- 9262940
TI  - Relationship between objective and subjective sleep measures in depressed
      patients and healthy controls.
AB  - The purpose of this study was to correlate subjective sleep characteristics based
      on questionnaire response, and objective sleep EEG features based on
      polysomnography, in 52 patients with major depressive disorders (MDD) and 49
      healthy controls. With the exception of the number of awakenings, subjective and
      objective sleep measures were strongly correlated in both groups. Patients and
      controls were able to accurately judge time in bed, total sleep time and sleep
      latency. However, sleep quality, depth, and how rested participants felt upon
      awakening were not strongly correlated with objective sleep characteristics,
      particularly in those with MDD. The findings suggest that estimates such as total
      sleep time and sleep latency, obtained from questionnaire data, bear a strong
      resemblance to objective polysomnographic characteristics in both those with MDD
      and healthy controls. Patients with MDD do not show sleep-state misperceptions
      although depressed women are more accurate in estimating sleep characteristics
      than depressed men.

PMID- 9262941
TI  - Effect of demographic and clinical variables on time to antidepressant response
      in geriatric depression.
AB  - The authors examined the effect of demographic and clinical variables on time to
      treatment response in geriatric depression. One hundred and one patients, aged 60
      92 years, with nonpsychotic, nonbipolar major depression were treated in an open
      fashion with 6 weeks of nortriptyline followed, if necessary, by 2 weeks of
      lithium augmentation. Univariate Cox proportional hazards analyses showed that 3
      of 19 variables predicted time to response: high baseline anxiety was associated
      with delayed response (median of 5 weeks vs. 4 weeks for patients with low
      anxiety scores), whereas hospitalization for the index episode of depression and
      attempted suicide predicted shorter time to response. In the final multivariate
      Cox regression model, baseline anxiety and inpatient status were most predictive
      of outcome; attempted suicide did not significantly improve the predictive power
      of the model. Our findings strengthen existing evidence that concomitant anxiety
      can adversely affect the outcome of geriatric depression.

PMID- 9262942
TI  - Reduced whole blood serotonin in major depression.
AB  - Whole blood serotonin (WBS) was measured in 17 patients with DSM-III-R major
      depression and compared to a healthy control group of 57. Values were
      significantly lower in the depressed group, but there was no correlation with the
      degree of depression. Four patients with a history of suicide attempts had even
      lower levels, but this was not statistically significant. Across all subjects,
      there was an effect of season of sampling, with values in spring significantly
      higher than those in autumn. Since blood serotonin is primarily produced
      peripherally, these results suggest that some aspect of peripheral serotonin
      metabolism is abnormal in major depression.

PMID- 9262943
TI  - Quantitative structure-activity relationships in substrates, inducers, and
      inhibitors of cytochrome P4501 (CYP1).

PMID- 9262944
TI  - Olestra, a nonabsorbed, noncaloric replacement for dietary fat: a review.
AB  - Olestra has been shown to be safe for its intended use by extensive testing in
      animals and in humans. It is not digested or absorbed and has no effect on the
      structure or physiology of the GI tract, the only organ of the body that it
      contacts. Olestra can interfere with the absorption of other lipophilic
      substances from the GI tract. The interference occurs because a portion of those
      molecules that are sufficiently lipophilic partition into the nonabsorbed olestra
      and is carried out of the body. Whether olestra will interfere with the
      absorption of a specific molecule can be predicted from the octanol-water
      partition coefficient of the molecule, a parameter that can be measured or
      calculated from a knowledge of the structure of the molecule. Olestra does not
      affect the absorption or efficacy of oral drugs because, in general, they are not
      sufficiently lipophilic to partition into the olestra. Olestra does not affect
      the absorption of water-soluble micronutrients or the absorption and utilization
      of macronutrients. Olestra can reduce the absorption of the fat-soluble vitamins
      when olestra foods and the vitamins are coingested. These effects can be offset
      by adding specific amounts of the vitamins to foods made with olestra. Other than
      the carotenoids and vitamins A and E, olestra does not affect the absorption of
      potentially beneficial components of fruits and vegetables. The effects on the
      vitamins can be offset by adding the vitamins to olestra foods. The reduction in
      the absorption of carotenoids will be less than 6-10% when olestra snacks are
      eaten under free-living dietary patterns. Any effect this reduction has on
      vitamin A status can be offset by addition of vitamin A to the foods. The
      absorption of flavonoids, polyphenols, and most other phytochemicals in fruits
      and vegetables, which have been shown to provide beneficial health effects, will
      not be affected by olestra because they are not sufficiently lipophilic.
      Individuals consuming large quantities of olestra may experience mild or moderate
      common GI symptoms such as loose or soft stools, gas, or nausea, symptoms similar
      to those experienced with certain other foods or changed dietary habits. When
      olestra snack foods are eaten under free-living dietary patterns, the symptoms
      are not different from those experienced when eating full-fat snack products, in
      either incidence or severity. When they are experienced, the symptoms resolve in
      1-2 days, but may recur. They do not worsen with continued or increased olestra
      consumption and pose no health risk to the consumer. Olestra products will carry
      an information label alerting consumers to the possibility of GI symptoms.
      Olestra foods provide an additional option to those individuals who want or need
      to lower their total energy intake and body weight. These individuals will find
      it easier to change dietary habits and to maintain healthful nutritional
      practices when they use olestra foods. For those who want or need to reduce fat
      intake but not lose weight, olestra foods can reduce fat intake without affecting
      energy. Because olestra foods have taste and other organoleptic properties that
      are similar to those of full-fat foods, individuals will find it easier to switch
      to low-fat diets.

PMID- 9262945
TI  - Directly coupled HPLC-NMR and its application to drug metabolism.

PMID- 9262946
TI  - Modeling the active sites of cytochrome P450s and glutathione S-transferases, two
      of the most important biotransformation enzymes.

PMID- 9262947
TI  - A history of drug metabolism in the United Kingdom.

PMID- 9262948
TI  - Drug metabolism: from experiments to regulatory aspects.

PMID- 9262949
TI  - Impact of heavy metals on water loss from lichen thalli.
AB  - Water loss in lichen species Cladonia convoluta (Lam.) and C. rangiformis (L.)
      Hoffm. after exposure to heavy-metal (Pb, Cu, or Zn) solutions, either as single
      compounds or in combination, have been studied in this laboratory. Water loss was
      reduced in Pb-treated C. convoluta, whereas in C. rangiformis it increased
      significantly with 10(-2) M Pb treatment. Water loss increased significantly (P =
      0.05) after Cu treatment in C. convoluta but was significantly reduced (P = 0.05)
      in 10(-8) and 10(-6) M CuCl2-treated C. rangiformis. Similarly, water loss
      increased in all Zn-treated thalli but was significantly decreased (P = 0.05) in
      10(-8) M treated C. rangiformis. A cumulative effect of Pb, Cu, and Zn was
      observed on water loss after uptake from mixed-metal solution. K+ efflux
      indicated the extent to which the plasma membrane presents an effective barrier
      to metal ion uptake.

PMID- 9262950
TI  - Added risk approach to derive maximum permissible concentrations for heavy
      metals: how to take natural background levels into account.
AB  - A unified method is presented to derive maximum permissible concentrations (MPCs)
      of xenobiotic and naturally occurring substances. The method relies upon risk
      limitation expressed as the maximum potentially affected fraction of all possible
      species (PAFmax) in a component ecosystem, due to a bioavailable concentration of
      the considered substance. For xenobiotic compounds the method is simplified to
      the "HC5 approach," i.e., the MPC equals the hazardous concentration at which 5%
      of the species are unprotected. If the natural background of a substance is
      (partly) bioavailable, the related background effect, also expressed as PAF, is
      taken into account in deriving a MPC. Examples are given and MPCs for zinc,
      chromium, cadmium, copper, and lead for different levels of bioavailability in
      water are developed.

PMID- 9262951
TI  - Absorption and degradation of metalaxyl in mustard plant (Brassica juncea).
AB  - Absorption and degradation of metalaxyl were studied in mustard (Brassica juncea)
      plants after application as a seed dresser, a foliar spray, and a combination of
      both under subtropical conditions in India. Results indicated that absorption of
      metalaxyl increased up to 30 days when it was applied as a seed dresser;
      thereafter, it started declining and was not detectable after 60 days of sowing.
      The maximum residues (average, 9.03 ppm) of metalaxyl were found after 1 day of
      spraying. The dissipation of metalaxyl after initial deposits on mustard plants
      was almost complete after 15 days of spraying. The safe waiting period of
      metalaxyl was calculated to be 62 and 8 days for seed dresser and foliar
      application, respectively. The seeds raised through treatments under study were
      completely free from any detectable amount of metalaxyl residues.

PMID- 9262952
TI  - Effects of temperature on the relative toxicities of Cd, Cu, Pb, and Zn to
      Folsomia candida (Collembola).
AB  - EC50s for cadmium, copper, lead, and zinc were determined for juvenile production
      of Folsomia candida Willem, 1902, at 25, 20, and 15 degrees C in a standard
      laboratory test system. Juvenile production of F. candida was too low at 25
      degrees C for reliable EC50-reproduction values to be determined. The EC50
      reproduction values (micrograms g-1) for cadmium, copper, and zinc were similar
      at both 20 and 15 degrees C (20 degrees C: Cd, 590; Cu, 700; Zn, 900; 15 degrees
      C: Cd, 540; Cu, 640; Zn, 590). Corresponding values for lead were considerably
      higher (20 degrees C: Pb, 2790; 15 degrees C: Pb, 1570). In aerially contaminated
      field sites adjacent to primary zinc smelters, zinc is invariably present in
      surface soils at concentrations of at least 50 times those of cadmium. The
      similarity of the EC50-reproduction values for cadmium and zinc in F. candida at
      20 and 15 degrees C determined in this study strongly suggests that deleterious
      effects of mixtures of these metals on populations of Collembola in such sites
      can be attributed to zinc rather than cadmium.

PMID- 9262953
TI  - Toxicity assessment of 16 inorganic environmental pollutants by six bioassays.
AB  - The relative toxicity of 16 environmental pollutants, such as inorganic elements
      (Ba, Cd, Co, Cr, Cu, Fe, Ge, Hg, Mn, Nb, Pb, Sb, Sn, Ti, V, and Zn), is evaluated
      on the L-929 established cell line of murine fibroblasts, with five bioassays
      [RNA synthesis rate assay (RNA), MTT reduction assay (MTT), neutral red
      incorporation assay (NRI), Coomassie blue assay, and cellular growth rate assay],
      and on the ciliated protozoa Tetrahymena pyriformis GL [doubling time of T.
      pyriformis GL population assay (DTP)]. For each inorganic substance, the six
      bioassays allowed the toxicological index IC50 ("inhibitory concentration 50%")
      to be calculated. The IC50 values are useful to rank the tested elements and to
      compare the features of the six bioassays. The most sensitive assays were the
      RNA, MTT, NRI, and DTP assays. Moreover, the in vitro IC50 values correlated with
      the in vivo LD50 values; these results were close to those obtained with
      established lines of human, murine, or fish cells. The sensitivity and the
      complementarity of these bioassays would be in favor of their incorporation in a
      "battery" of tests used for toxicological screening studies of xenobiotics.

PMID- 9262954
TI  - BSD extent, an index for metal pollution screening based on the metal content
      within digestive cell lysosomes of mussels as determined by autometallography.
AB  - The extent of autometallographical black silver deposits (BSD) has been
      semiquantified at the light microscope in the gills and digestive gland of either
      control mussels or Zn-polluted mussels after depuration and on exposure to
      sublethal concentrations of Cu, Zn, and Cd. The BSD extent in the gills and
      digestive gland of control mussels was much reduced compared to that in other
      experimental mussels. The extent of BSD in the gills of depurating mussels was
      reduced at short depuration times due to decreased levels in the abfrontal cells
      while in the digestive gland it did not change with the depuration period. The
      extent of BSD in digestive lysosomes of Cu- and Zn-exposed mussels followed a
      logarithmic pattern in relation to metal concentration increasing with metal
      concentrations in the digestive gland. However, a reduced extent of BSD was
      related to the presence of high metal concentrations under Cd-exposure
      conditions. This is because the great extent of BSD present in the lumen of the
      digestive tubules was not taken into account to carry out semiquantification,
      but, however, the chemical analysis measured the Cd content of these BSD. As
      such, the extent of BSD in digestive lysosomes followed a logarithmic pattern
      with total metal concentrations in the digestive gland of Cd-exposed mussels.
      Therefore, the semiquantitative estimation of BSD in the digestive lysosomes
      could be considered a reliable index to reflect changes in metal bioavailability
      in sea water.

PMID- 9262955
TI  - Cell integrity markers for in vitro evaluation of cytotoxic responses to bacteria
      containing commercial insecticides.
AB  - Toxicity of two commercial "BT" products, containing Bacillus thuringiensis
      subsp. kurstaki spores (Btk) and associated parasporal inclusion body proteins,
      was tested in vitro using two unrelated lepidoperan cell lines and several
      markers of cell integrity (morphology, quantification of loss of adherence and
      electron transport (redox) activity, and degradation of nuclear DNA, actin, hsp
      70, and beta-tubulin). With doses of 10(-7), 10(-5), and 10(-3) International
      Units (IU)/target cell, these markers measured exposure-dependent effects closely
      linked to cell death, which occurred rapidly once Btk spores germinated, unless
      inhibited by antibiotic. Derivation of marker half-lives (HL50) revealed that
      temperature critically affected product performance. Between 34 and 37 degrees C,
      HL50 was < or = 5 hr, but dose discrimination between 10(-5) and 10(-3) IU was
      poor. At temperatures less than 34 degrees C, the resolution between different
      HL50s and doses increased in a manner directly relating to published data
      obtained from in vivo BT-spore-induced LD50 assays. It was concluded that BT
      product toxification is complex, essentially enabled by an autobiotransformation
      process in which dose-response lag is affected by temperature-dependent temporal
      expression of spore germination and critical buildup of vegetative cells and
      byproduct toxicants. The in vitro dosimetry assays described here are potentially
      useful for obtaining mechanistic toxicologic data and in vivo relevant
      quantifications of subingredient activities in various commercial BT formulations
      as well as in other microbe-based biotechnology products.

PMID- 9262956
TI  - A conceptual framework for implementation of bioavailability of metals for
      environmental management purposes.
AB  - Although bioavailability is an important issue, the scientific basis for its
      adequate use in the assessment of ecological risks is weak. What is often ignored
      is that bioavailability should be handled as a dynamic process that comprises two
      distinct phases: a physicochemically driven desorption process (also referred to
      as "environmental availability") and a physiologically driven uptake process
      (also referred to as "environmental bioavailability"). Since the internal
      concentration of the organism (also referred to as "toxicological
      bioavailability") is related with organ-effect levels, it is the latter that is
      determinant for the actual bioavailability. On the basis of contemporary ideas on
      equilibrium partitioning both within soils and between soils and organisms
      combined with a detailed literature review, in this contribution a framework is
      presented aimed at providing a guidance to necessary components of risk
      assessment procedures that take bioavailability into account. The framework
      provides suggestions with regard to the design and scope of studies to be carried
      out. It is based on knowledge on physico-chemical metal partitioning, in
      combination with models and concepts applied to analyse toxico-kinetics in
      exposed organisms. The conceptual dynamic framework boils down to a description
      of the system in the form of equilibria. It is assumed that each biotic species
      can be considered as one of the soil phases next to the particulate phase and the
      liquid phase. Each phase has a characteristic set of exposure routes.
      Equilibration processes are assumed to take place between all phases present.
      Essential is that the plan should result in validated procedures that, because
      they will explicitly address the issue of availability, will be predictive of
      effects in systems that have not been biologically tested.

PMID- 9262957
TI  - Ecotoxicity hazard assessment of styrene.
AB  - The ecotoxicity of styrene was evaluated in acute toxicity studies of fathead
      minnows (Pimephales promelas), daphnids (Daphnia magna), amphipods (Hyalella
      azteca), and freshwater green algae (Selenastrum capricornutum), and a subacute
      toxicity study of earthworms (Eisenia fostida). Stable exposure levels were
      maintained in the studies with fathead minnows, daphnids, and amphipods using
      sealed, flowthrough, serial dilution systems and test vessels. The algae were
      evaluated in a sealed, static system. The earthworms were exposed in artificial
      soil which was renewed after 7 days. Styrene concentrations in water and soil
      were analyzed by gas chromatography with flame ionization detection following
      extraction into hexane. Test results are based on measured concentrations.
      Styrene was moderately toxic to fathead minnows, daphnids, and amphipods: fathead
      minnow: LC50 (96 hr), 10 mg/liter, and NOEC, 4.0 mg/liter; daphnids: EC50 (48
      hr), 4.7 mg/liter, and NOEC, 1.9 mg/liter; amphipods: LC50 (96 hr), 9.5 mg/liter,
      and NOEC, 4.1 mg/liter. Styrene was highly toxic to green algae: EC50 (96 hr),
      0.72 mg/liter, and NOEC, 0.063 mg/liter; these effects were found to be
      algistatic rather than algicidal. Styrene was slightly toxic to earthworms: LC50
      (14 days), 120 mg/kg, and NOEC, 44 mg/kg. There was no indication of a concern
      for chronic toxicity based on these studies. Styrene's potential impact on
      aquatic and soil environments is significantly mitigated by its volatility and
      biodegradability.

PMID- 9262958
TI  - Mitochondrial myopathy in Senna occidentalis-seed-fed chicken.
AB  - Plants of the genus Senna (formerly Cassia) have been recognized as the cause of
      a natural and experimental syndrome of muscle degeneration frequently leading to
      death in animals. Histologically, it demonstrated skeletal and cardiac muscle
      necrosis, with floccular degeneration and proliferation of sarcolemmal nuclei.
      Recently, it was described as an experimental model of mitochondrial myopathy in
      hens chronically treated with Senna occidentalis. Currently, skeletal muscles of
      chicks intoxicated with seeds of the poisonous plant S. occidentalis were studied
      by histochemistry and electron microscopy. Since birth, the birds were fed ground
      dried seeds of this plant with a regular chicken ration at a dose of 4% for 11
      days. Microscopic examination revealed, besides muscle-fiber atrophy, lipid
      storage in most fibers and a moderate amount of cytochrome oxidase-negative
      fibers. By electron microscopy, enlarged mitochondria with disrupted or
      excessively branched cristae were seen. This picture was characteristic of
      mitochondrial myopathy. These findings have hitherto remained unnoticed in
      skeletal muscle of young birds treated with S. occidentalis.

PMID- 9262960
TI  - The role of cytokines in ultraviolet-B induced immunosuppression.
AB  - Cytokines play an important role in the mechanisms resulting in ultraviolet B
      induced immunosuppression. They play a crucial role in the induction of local as
      well as systemic immunomodulatory events. Ultraviolet B irradiation directly
      induces the release of cytokines in the epidermis, resulting in complex and
      diverse interactions on epidermal cells, which results in migration out of the
      skin and infiltration into the skin of different cell types. Partly because of
      the interaction of locally produced cytokines with antigen-presenting cells,
      systemic effects, such as antigen-specific tolerance, can be observed. This
      review describes the different mechanisms whereby ultraviolet B exposure affects
      immune functions with special emphasis on the role of T-cell subsets and
      cytokines.

PMID- 9262959
TI  - Relative sensitivity of three endangered fishes, Colorado squawfish, bonytail,
      and razorback sucker, to selected metal pollutants.
AB  - The acute toxicity of four metal pollutants to larval and juvenile stages of
      endangered Colorado squawfish (Ptychocheilus lucius), bonytail (Gila elegans),
      and razorback sucker (Xyrauchen texanus) were determined in a water quality
      representative of that in the Green River, Utah. The rank order of toxicity (96
      hr LC50) of the metals to all species and life stages from most toxic to least
      toxic was mercury (57-168 micrograms/liter) > cadmium (78-168 micrograms/liter) >
      hexavalent chromium (32,000-123,000 micrograms/liter) > lead (> 170,000
      micrograms/liter). In tests with lead, a precipitate formed in all test solutions
      and no mortalities occurred in these treatments. The larvae of each species were
      as sensitive or more sensitive than the juveniles to cadmium, hexavalent
      chromium, and mercury. Overall, the three species exhibited similar sensitivities
      to cadmium, hexavalent chromium, and mercury. Comparison of test results for the
      juveniles with toxicity values reported for other freshwater fishes tested in
      different water qualities indicates that the endangered fishes are more sensitive
      to cadmium than other cyprinids and centrarchids and less sensitive than
      salmonids, whereas their sensitivity to hexavalent chromium and mercury is
      similar to that of other cyprinids, centrarchids, and salmonids.

PMID- 9262961
TI  - Macrophage colony-stimulating-factor (M-CSF or CSF-1) and its receptor: structure
      function relationships.

PMID- 9262962
TI  - Production of ovarian cytokines and their role in ovulation in the mammalian
      ovary.
AB  - Cytokines, originally identified as products of immune cells, are synthesized
      throughout the female reproductive tract. Evidence has accumulated supporting the
      role of cytokines in reproduction, including gamete and follicle development and
      steroidogenesis. In these processes, cytokines act either through a paracrine or
      autocrine mechanism. The present article focuses on the role of cytokines during
      ovulation, which shares many of the features of the inflammatory reaction. The
      intraovarian production of cytokines, as well as its regulation by sex steroid
      and peptide hormones, is considered. The role of cytokines in follicle rupture
      and remodelling, leukocyte infiltration, angiogenesis, steroid hormone production
      and oocyte maturation is also described.

PMID- 9262963
TI  - Cytokines and peripheral nerve disorders.
AB  - Peripheral nerve production of cytokines originates from resident and recruited
      macrophages, lymphocytes, mastocytes, Schwann cells, and probably neurons.
      Cytokines are involved in nerve lesions and repair. Tumor necrosis factor-alpha
      (TNF-alpha) injected into nerve induces Wallerian degeneration, whereas,
      interleukin-1 (IL-1) production promotes detersion by scavenger macrophages, and
      synthesis of neurotrophic factors (nerve growth factor-NGF- and leukemia
      inhibitory factor-LIF). After experimental axotomy, other neurotrophic factors,
      including IL-6, LIF and transforming growth factor-beta 1 (TGF-beta 1), are
      overexpressed in nerve and promote axonal growth until axon/Schwann cell contact.
      Proinflammatory cytokines are instrumental in the course of inflammatory
      demyelinating neuropathies. They increase vascular permeability and blood nerve
      barrier breakdown (TNF-alpha, vascular endothelial growth factor/ vascular
      permeability factor-VEGF/VPF), favor transmigration of leukocytes into nerve,
      induce activation and proliferation of lymphocytes (IL-1, IL-2) and macrophages
      (gamma-interferon-IFN-gamma), and have a direct myelinotoxic activity (TNF-alpha
      and TNF-beta). In addition, downregulation of the immunosuppressive cytokine TGF
      beta 1 may favor the nerve inflammatory reactions.

PMID- 9262964
TI  - Interleukin-10-mediated T cell apoptosis during the T helper type 2 cytokine
      response in murine Schistosoma mansoni parasite infection.
AB  - The pathogenesis of infection with the helminth parasite Schistosoma (S) mansoni
      in mice has been reported to involve a T helper (Th)1 to Th2 cytokine switch,
      associated with a pathogenic granulomatous response to parasite eggs and to a
      global defect in Th1-cell effector functions. Here we report that the Th2
      cytokine response, which begins 6 weeks after infection, at the time of parasite
      egg laying (i) does not occur in the context of a genuine Th1 to Th2 cytokine
      switch, but is associated with a persistent capacity of Th1 (or Th0) cells to
      secrete IL-2 and IFN-gamma in response to T cell receptor (TCR) stimulation; (ii)
      is associated, in vitro, with spontaneous death by apoptosis of a significant
      fraction of the CD4 and CD8 T cells, which is greatly enhanced by TCR
      stimulation; and (iii) is associated, in vivo, with numerous and large clusters
      of apoptotic cells in the spleen and in the inflammatory infiltrates surrounding
      the parasite egg deposits in the liver. The in vitro addition of antibodies to
      the Th2 cytokine IL-10 had both a preventive effect on TCR-induced T cell
      apoptosis and an enhancing effect on TCR-induced T cell secretion of Th1
      cytokines. Taken together, these findings suggest that the downregulation of Th1
      cell-mediated effector functions in S. mansoni-infected mice may not be related
      to a lack of Th1 cell production, but to a process of IL-10-mediated and
      activation-induced premature T cell death, that include Th1 (or Th0) cells.
      Further identification of mechanisms involved in the regulation of T cell
      apoptosis has implications for the understanding of the pathogenesis of
      immunosuppression associated with chronic infectious diseases.

PMID- 9262965
TI  - Functional epitope mapping of human interleukin-1 beta by surface plasmon
      resonance.
AB  - A panel of monoclonal antibodies to human IL-1 beta has been used to probe its
      conformational and functional characteristics. Real time antibody-protein
      interaction was assessed by surface plasmon resonance with a BIAcore apparatus,
      in order to determine the kinetic and thermodynamic parameters of the interaction
      and to map the recognition sites of the antibodies on the IL-1 beta surface.
      Topological analysis was thus compared to the inhibitory capacity of antibodies
      for IL-1 beta bioactivity and binding to the activating receptor IL-1RI. This
      functional mapping analysis allows the following hypothesis. At least two
      discrete areas of IL-1 beta, located within the sequences 133-147 and 177-186 (as
      defined by mAbs MhC1 and BRhD2, respectively), are apparently involved in IL-1RI
      independent agonist activity, and thus possibly take part in the interaction with
      the receptor accessory protein IL-1RAcP. Another area in the 133-147 sequence
      (defined by mAb BRhC3) is involved in agonist binding to its receptor CDw121a (IL
      1RI), whereas a site recognized by mAb BRhG5 within the sequence 218-243 is
      selectively responsible for non-agonist binding to the activating receptor. The
      loop between the 4th and the 5th beta-strand, at the open end of the IL-1 beta
      barrel structure, may possibly take part in both non-agonist binding to IL-1RI
      and in the interaction with IL-1RAcP.

PMID- 9262966
TI  - Interleukin-1 beta primes interleukin-8-stimulated chemotaxis and elastase
      release in human neutrophils via its type I receptor.
AB  - Interleukin-1 (IL-1) is a pleiotropic proinflammatory cytokine which binds to
      human neutrophils (PMN) and can directly or indirectly activate their functions.
      In this study we show that a brief exposure to IL-1 beta induces a potentiation
      of both PMN elastase release and chemotactic response to interleukin-8 (IL-8),
      the prototype of C-X-C chemokines. Priming by IL-1 beta was maximal at 100 ng/ml,
      was completely blocked in the presence of IL-1 receptor antagonist (IL-1ra) and,
      in the chemotaxis assay, was best observed at suboptimal (3-6 ng/ml) or inactive
      (0.75 ng/ml) concentrations of IL-8. Priming of PMN by IL-1 beta was completely
      blocked by M1, a specific antibody against the type I IL-1 receptor (IL-1RI). On
      the other hand M22, an antibody directed against the IL-1 decoy type II IL-1
      receptor did not affect IL-1 beta action and slightly increased the priming
      effect. Thus, exclusively via its type I receptor, IL-1 beta can act on PMN at
      multiple levels, by promoting their accumulation in tissues through the induction
      of chemotactic factors (e.g. IL-8) and the upregulation of adhesion molecules,
      and by priming their response to chemotactic agonists.

PMID- 9262967
TI  - Distinct patterns of expression of interleukin-1 alpha and beta by normal and
      cancerous human ovarian tissues.
AB  - Immunohistochemical staining of normal and cancerous ovarian tissues has
      demonstrated that both IL-1 alpha and IL-1 beta are more strongly expressed in
      cancerous than in normal tissues and are secreted mainly by epithelial cells. We
      have shown by bioassay and immunoassay that cancerous, but not normal ovarian
      tissues constitutively secrete IL-1 in vitro. Activation of cancerous ovarian
      tissues by lipopolysaccharide (LPS) increased its capacity to secrete IL-1.
      Normal ovarian tissues secreted low amounts of IL-1 only after prolonged
      stimulation (72-96 h) by high doses of LPS (10-100 micrograms/ml). On the other
      hand, constitutive IL-1 was detected in homogenates of normal ovarian tissues and
      stimulation by LPS increased its capacity to produce IL-1. IL-1 beta was the main
      type of IL-1 secreted by cancerous ovarian tissues. IL-1 alpha was detected at
      lower levels. In contrast, in normal tissues similar amounts of both IL-1 alpha
      and IL-1 beta were detected in the supernatants. The levels of both types of IL
      1, and also the bioactivity of IL-1 were significantly higher in cancerous than
      in normal ovarian tissues. Established primary cell lines from normal ovarian
      tissues did not secrete IL-1 into supernatants but did express it at very low
      levels. Stimulation with LPS did not affect the capacity of these cell lines to
      secrete IL-1 but it increased their capacity to express it. In contrast, primary
      established epithelial cell lines from cancerous ovarian tissues did secrete and
      express high levels of IL-1 and these levels were increased under stimulation
      with LPS. Cancerous ovarian tissues did not only secrete higher levels of both IL
      1 alpha and beta than normal ovarian tissues, but also the mechanism controlling
      the secretion of these factors in cancerous ovarian tissues seemed to be
      different from that found in normal ovarian tissues. Our results suggest that
      paracrine/autocrine factors may be involved in the regulation of both types of IL
      1 secreted by ovarian tissues. These cytokines may play a role in regulating the
      physiological, pathophysiological and oncogenic processes of the ovary.

PMID- 9262968
TI  - Interleukin-13 effects on activated monocytes lead to novel cytokine secretion
      profiles intermediate between those induced by interleukin-10 and by interferon
      gamma.
AB  - We have examined in detail the activities of IL-13 on monokine production in
      vitro and compared its effects with those of IL-10 and IFN-gamma. IL-13 and IL-10
      show qualitatively and quantitatively similar activities on cytokine production
      by monocytes when administered simultaneously with LPS i.e. inhibition of IL-1,
      IL-6 and TNF-alpha, up-regulation of IL1-ra. However when either LPS and IFN
      gamma or fixed S. aureus Cowan (SAC) are used to activate monocytes, IL-10 is a
      much more potent inhibitor of TNF-alpha production than is IL-13. IL-10 is also
      an extremely potent inhibitor of IL-12 (p70) production when given with either
      SAC or LPS, while IL-13 has little effect. Indeed, IL-13 actually increases SAC
      induced IL-12 production. When IL-13 is administered prior to the LPS
      stimulation, its modulation of cytokine production is drastically different.
      Production of IL-12, MCP-1, TNF-alpha and to a lesser extent IL-6 induced by LPS
      is now "primed", whereas that of IL-1, IL-8, and IL-10 is still inhibited. IL-10
      does not show this "priming" effect, and is a dominant inhibitor of IL-13. The
      initial IL-13 priming effect is not however due to an inhibition of endogenous IL
      10 production; nor is it due to inhibition of PGE2 production. The priming effect
      of IL-13 on IL-12 production is additive with that of IFN-gamma, and is partly
      independent of IFN-gamma. The earliest event in IL-13 priming so far noted is an
      increase in TNF-alpha mRNA production at 1-2 hours. IL-13 priming of IL-12
      production can be completely abolished by anti-TNF-alpha antibodies suggesting
      that IL-13 may be priming via increased TNF-alpha expression, although merely
      substituting TNF-alpha for IL-13 does not reproduce the priming effect. IL-13 is
      a thus a more subtle immune regulator than IL-10 or IFN-gamma. When administered
      with LPS or SAC, it dampens the resulting inflammatory response, though in a more
      selective way than IL-10. In contrast, when it is added before an inflammatory
      signal, it primes an immunostimulatory monokine secretion profile resembling that
      of IFN-gamma, but without the proinflammatory IL-1 component. Early in response
      to an inflammatory stimulus, IL-13 may thus play an essentially anti-inflammatory
      role, switching to a primarily immunostimulatory role in the case of an ongoing
      infection.

PMID- 9262970
TI  - Interferons and cytokines: where we stand after the first joint meeting of the
      International Cytokine Society and the International Society for Interferon and
      Cytokine Research (Geneva, October 6-10, 1996).

PMID- 9262969
TI  - The related cytokines interleukin-13 and interleukin-4 are distinguished by
      differential production and differential effects on T lymphocytes.
AB  - We have compared the production of the related cytokines IL-13 and IL-4 by T
      lymphocytes, and the effects of the two cytokines on these cells. IL-13 and IL-4
      production differ in a number of respects. IL-13 is produced at higher levels
      than IL-4 by activated T lymphocytes, and its accumulation in the culture medium
      can be more prolonged, corresponding partly to differential mRNA accumulation and
      partly to a preferential depletion of IL-4 from the culture medium. Certain
      inducing combinations such as PMA and anti-CD28, stimulate high levels of IL-13
      and IL-13 mRNA, but little or no IL-4 or IL-4 mRNA. The ratio of IL-13 to IL-4,
      both at protein and mRNA levels, is higher in CD8+ lymphocyte than in CD4+
      lymphocyte populations. Although after in vitro polarization of peripheral blood
      lymphocytes leading to type 1 and type 2 populations, IL-13 is made principally
      by cells of a type 2 phenotype, as is IL-4; it can also be produced by type 1
      CD4+ and CD8+ T lymphocyte clones making large amounts of IFN-gamma and very
      little IL-4. IL-13 and IL-4 exert different effects on T lymphocyte functions. IL
      13 does not significantly inhibit the IL-2-induced T lymphocyte production of IFN
      gamma, RANTES, MIP-1 alpha or MIP-1 beta, nor that of perforin mRNA, as does IL
      4. We have also been unable to demonstrate STAT6 activation by IL-13 on T
      lymphocytes purified in a number of ways, despite strong activation of STAT6 by
      IL-4 in these cells. This is contrary to some previous reports, but is consistent
      with the notion that the majority of T lymphocytes lack functional IL-13
      receptors. A higher and more prolonged T lymphocyte production of IL-13 than that
      of IL-4 may thus be permissible because IL-13 does not inhibit T-cell functions.
      Conversely, sustained IL-13 production may be partly due to the absence of
      receptor-mediated depletion of this cytokine.

PMID- 9262971
TI  - Endomysium: autoantigen in coeliac disease.
AB  - In coeliac disease, dietary exposure to gluten is associated with an autoimmune
      response to gastrointestinal antigens, including endomysium. Measurement of
      autoantibodies to endomysium is a highly specific and sensitive method of
      diagnosing coeliac disease. Analysis of the interaction between gluten and
      endomysium should provide a critical insight into the pathogenesis of this
      condition.

PMID- 9262972
TI  - Is human umbilical cord the most suitable substrate for the detection of
      endomysium antibodies in the screening and follow-up of coeliac disease?
AB  - BACKGROUND: Immunoglobulin A (IgA) anti-endomysium antibodies, the most reliable
      immunological marker for both the screening and follow-up of coeliac disease,
      need monkey oesophagus as antigenic substrate; this limits their use because of
      high costs and the exploitation of endangered species. OBJECTIVES: (1) To compare
      the diagnostic accuracy of anti-endomysium antibodies detected by indirect
      immunofluorescence on monkey oesophagus and on human umbilical cord; (2) to
      evaluate their reliability during follow-up in detecting non-compliant patients.
      PATIENTS: One hundred and four untreated adults with biopsy-proven coeliac
      disease and 94 controls were investigated. RESULTS: Endomysium antibodies were
      found in 99 patients (95%) on both substrates, with a specificity, respectively,
      of 100% and 99% on monkey oesophagus and umbilical cord. One year after gluten
      withdrawal, out of 47 patients who were investigated, only six presented with
      complete mucosal recovery: none of these subjects was positive on either
      substrates, while, among patients with persistent histological alterations,
      endomysium positivity persisted in only 10 on monkey oesophagus, but in 32 on
      umbilical cord. Histology (recovery or persistent involvement) was in agreement
      with endomysium (negative or positive) in 34% on monkey oesophagus, but in 81% on
      umbilical cord (P < 0.0001). CONCLUSION: Human umbilical cord, with its
      comparable diagnostic efficiency, could replace monkey tissues, with the
      advantages of saving both money and monkeys. Moreover, it seems the most suitable
      substrate in the follow-up, as it enables detection of non-compliant patients
      with persisting mucosal alterations.

PMID- 9262973
TI  - IgM antibody against measles virus in patients with inflammatory bowel disease: a
      marker of virus-related disease?
AB  - OBJECTIVE: Viral infections of the mesenteric microvascular endothelium have been
      hypothesized as pathogenetic factors in inflammatory bowel diseases. The aim of
      this study was to determine whether immunoglobulin M (IgM) antibody against
      measles virus is associated with disease. PATIENTS AND METHODS: The IgM antibody
      was detected by indirect antibody test in 36 patients with evidence of Crohn's
      disease (23 males and 13 females, median age 40 years, range 20-66), 22 patients
      with ulcerative colitis (14 males and 8 females, median age 42 years; range 19
      65), 59 patients with a chronic active hepatitis (35 males and 24 females, median
      age 56 years, range 38-77) and 30 blood donors (20 males and 10 females, median
      age 45 years, range 29-62). RESULTS: Twenty-eight of 36 patients (78%) with
      Crohn's disease and 13 of 22 patients (59%) with ulcerative colitis tested
      positive as compared to only 3 of 89 (3.3%) controls (P < or = 0.001).
      CONCLUSION: The detection of IgM anti-measles virus in the majority of patients
      with Crohn's disease and in about half of ulcerative colitis patients as compared
      to a very low prevalence in patients with other chronic inflammatory disease is
      consistent with the hypothesis that the measles virus has pathogenetic
      implications in inflammatory bowel diseases.

PMID- 9262975
TI  - Do patients with systemic sclerosis have abnormal gallbladder function?
AB  - OBJECTIVE: To determine gallbladder motility in patients with systemic sclerosis.
      DESIGN: Case control study. SETTING: University hospital, out-patient department
      of rheumatology. PATIENTS: Ten patients with systemic sclerosis according to the
      criteria of the American Rheumatism Association with documented involvement of
      the gastrointestinal tract and 10 healthy controls matched for age, sex and body
      mass index. INTERVENTION: Cephalic vagal cholinergic simulation by modified sham
      feeding and hormonal stimulation by infusion of cholecystokinin. MEASUREMENTS:
      Gallbladder volume obtained by ultrasonography and determination of plasma
      cholecystokinin concentrations. RESULTS: Fasting gallbladder volumes were not
      significantly different between patients with systemic sclerosis and controls
      (19.6 +/- 1.9 cm3 and 23.3 +/- 2.9 cm3, respectively, mean plus or minus standard
      error of the mean). Neither were there significant differences in reduction of
      gallbladder volume in response to modified sham feeding (35 +/- 4% and 33 +/- 4%,
      respectively) nor during cholecystokinin infusion (56 +/- 4% and 60 +/- 6%,
      respectively). The increase in plasma cholecystokinin levels during infusion was
      not different in the two groups. CONCLUSION: Gallbladder motility in patients
      with systemic sclerosis is preserved in response to both cholinergic and hormonal
      stimulation, even when other gastrointestinal motor disturbances are present.
      These results suggest that patients with systemic sclerosis are not at increased
      risk for cholelithiasis because of gallbladder dysmotility.

PMID- 9262974
TI  - Indomethacin influences regulatory peptides and increases DNA synthesis in the
      gastrointestinal tract of the rat.
AB  - OBJECTIVE: To examine the effect of long-term administration of indomethacin on
      regulatory peptides and DNA synthesis. DESIGN: Sprague-Dawley rats were treated
      with 1 mg/kg indomethacin subcutaneously or indomethacin and 500 micrograms/kg
      oral prostaglandin E2 or solvents for 2 months before labelling with methyl-3H
      thymidine. METHODS: The labelling index, growth fraction and the number of
      epithelial cells were determined on autoradiographs of the stomach small
      intestine and colon. Plasma and gastrointestinal tissue concentrations of
      regulatory peptides were analysed by radioimmunoassay. RESULTS: Indomethacin
      increased the concentration of somatostatin in the gastric fundus and ileum and
      reduced it in the colon. Prostaglandin E2 reduced the somatostatin concentration
      in the duodenum and colon. Indomethacin increased the concentration of
      neurotensin neurokinin A and glucagon in the distal small intestine and reduced
      the glucagon level in the colon. Prostaglandin E2 prevented such changes.
      Indomethacin increased DNA synthesis in the small intestine and produced
      hypoplasia of the villi. These changes were prevented by prostaglandin E2, except
      for the villous hypoplasia observed in the distal small intestine. Prostaglandin
      E2 reduced the labelling index in the antrum and colon. CONCLUSION: Endogenous
      prostaglandins selectively modulate the synthesis and/or release of regulatory
      peptides and regulate the outflow of cells from the epithelial surface.
      Indomethacin induces hypoplasia, which triggers a secondary trophic reaction in
      the epithelium that may, at least partially, be mediated by regulatory peptides.

PMID- 9262976
TI  - The ursodeoxycholic acid-p-aminobenzoic acid deconjugation test, a new tool for
      the diagnosis of bacterial overgrowth syndrome.
AB  - OBJECTIVE: To determine the possible complementary role of the ursodeoxycholic
      acid-p-aminobenzoic acid (UDCA-PABA) loading test in the diagnosis of intestinal
      bacterial overgrowth. DESIGN: A prospective clinical study. PATIENTS AND METHODS:
      The hydrogen breath and UDCA-PABA tests were performed simultaneously in 68
      patients with suspected contaminated small bowel syndrome (CSBS), and in 10
      healthy control subjects. The hydrogen breath test was performed by oral loading
      of 25 g of lactose and/or 10 g of lactulose. The UDCA-PABA test was carried out
      by oral loading of 250 mg of UDCA-PABA conjugate, followed by measurement of the
      amount of PABA excreted in the urine. The diagnosis of bacterial overgrowth was
      considered to be established when either the hydrogen breath test or the UDCA
      PABA test produced abnormal results. RESULTS: Thirty-five of the 68 patients
      proved to have CSBS. In 13 of these 35 patients, only the enhanced urinary PABA
      excretion (11.7 +/- 1.42 mg vs. 3.6 +/- 0.68 mg) indicated bacterial overgrowth,
      15 of the 35 patients gave only a positive hydrogen breath test, and in the
      remaining seven cases the results of both tests were abnormal. In eight CSBS
      patients, the urinary excretion of PABA was decreased significantly following 10
      day tinidazole treatment (5.5 +/- 1.29 mg vs. 13.1 +/- 2.07 mg). CONCLUSION: The
      UDCA-PABA test is a valuable clinical method for the detection of bacterial
      overgrowth, especially in cases where hydrogen production alone fails to reveal
      CSBS. It is also a useful procedure for evaluating the efficacy of antibacterial
      treatment.

PMID- 9262977
TI  - Effects of smoking on the presentation and clinical course of inflammatory bowel
      disease.
AB  - OBJECTIVE: To evaluate the influence of regular smoking on the presentation and
      clinical course of inflammatory bowel disease. METHODS: We performed a case
      control study interviewing 160 inflammatory bowel disease patients (63 with
      Crohn's disease (CD) and 97 with ulcerative colitis (UC)) and 140 first-degree
      relatives as controls. The risk of developing the disease relative to a smoking
      habit was calculated as the odds ratio. Furthermore, to evaluate the influence of
      smoking on the subsequent course of inflammatory bowel disease, we performed a
      multivariate analysis that included pertinent variables such as the need for
      surgery, number of hospitalizations and relapses. RESULTS: The pattern of smoking
      in UC patients was different from that in CD patients. In UC there was a
      significant predominance of non-smokers and ex-smokers (P = 0.02), whereas
      smoking habits in CD were not different from those in controls. Giving up smoking
      was a risk factor to develop UC (odds ratio: 3.2, P = 0.02). In UC, non-smokers
      and specially ex-smokers need surgery more frequently than smokers (P < 0.01).
      Otherwise the relapse/year index was not influenced by smoking. In CD there was a
      non-significant association between smoking habits and the various clinical
      parameters analysed. UC patients who begin smoking after diagnosis of the disease
      present a significant reduction in the number of recurrences. CONCLUSION: Smoking
      habit significantly affects the presentation and clinical course of UC, whereas
      in CD, a smoking habit does not have any apparent influence on the disease.

PMID- 9262978
TI  - Irritable bowel syndrome: the view from general practice.
AB  - OBJECTIVE: To determine the attributes of the irritable bowel syndrome (IBS) in
      general practice as perceived by the doctors. SUBJECTS AND METHODS: We
      administered a 93-item questionnaire about the terminology, diagnosis and
      treatment of the irritable bowel to 43 of 55 randomly selected general
      practitioners (28 men, 15 women). RESULTS: General practitioners were unfamiliar
      with the Manning criteria for the irritable bowel syndrome. Nevertheless, most of
      them diagnosed the irritable bowel with reasonable confidence and it is less
      troublesome to them than pelvic pain, headache or backache. Their main concern
      was excluding organic disease (63%) and 65% believed their patients shared this
      concern. Nevertheless, they ordered few tests and were often (72%) prepared to
      make the diagnosis on the initial visit. They estimated that they referred only
      14% of IBS patients to specialists, in most cases (56%) because of an unsatisfied
      patient and in 35% because of an uncertain diagnosis. For treatment, most (77%)
      chose 'explanation and reassurance'. Virtually all employed drugs, usually
      several. CONCLUSION: General practitioners say they diagnose the irritable bowel
      syndrome with less difficulty than other common, painful disorders, but it would
      be helpful to find out exactly how they do so. Their confidence could be
      increased by use of diagnostic criteria. Patients referred to specialists are
      likely to be a minority of hard-to-satisfy people. The optimal approach to such
      patients should be developed by general practitioners and specialists together.
      Specialists should strive to satisfy the patient and confirm the diagnosis in the
      few that are referred. Drug usuage in the irritable bowel syndrome is more than
      is justified and should, in our view, be minimized.

PMID- 9262979
TI  - The breath test--a call for more regional use.
AB  - OBJECTIVE: Although the 13C-urea breath test is commonly used for detection of
      Helicobacter pylori infection and eradication, access to commercial testing
      centres for analysis may at times limit its use. We have addressed this issue by
      establishing a regional-based means of analysis as a Hospital-University
      collaboration. DESIGN/METHODS: A blind comparison was undertaken of 13C-urea
      breath test results performed 'in house' by the stable isotope laboratory in
      Queen's University Belfast and a commercially available 13C-urea breath test.
      RESULTS: The H. pylori status of the patients (n = 110) agreed for all patients
      (kappa score = 1). The excess values showed good agreement. The cost of the 'in
      house' breath test was less than 20 pounds compared with 32.90 pounds for the
      commercial breath test. CONCLUSION: Regional access to the 13C-urea breath test
      could decrease costs, increase availability of testing, improve local health
      services and economy and increase collaborative research opportunities.

PMID- 9262980
TI  - Radiolucent pancreatic lithiasis: a precursor stage for calcified pancreatic
      lithiasis or a new entity?
AB  - OBJECTIVE: Radiolucent pancreatic lithiasis (RPL) has been identified as a
      different entity from calcified pancreatic lithiasis. The purpose of this study
      is to evaluate the frequency, characteristics and evolution of RPL. PATIENTS:
      Between 1983 and 1995, 278 consecutive patients who presented with pancreatic
      lithiasis were studied. Forty-four patients had RPL (15.8%): 27 had pure
      radiolucent stones (PRS) (group 1), 5 had pure radiolucent stones combined with
      evenly calcified stones (ECS) (group 2), 2 had target calculi (TC) (radiolucent
      core with calcified shell) (group 3), 10 had TC combined with ECS (group 4).
      RESULTS: Among the 27 patients with PRS, there were 19 males with a mean age of
      41 years. PRS were mainly located in the head of the pancreas with a mean
      diameter of 5 mm (range 3-26 mm). Seven patients among 27 with PRS (26%) were
      less than 20 years old (juvenile form) or more than 60 years old (senile form).
      They were characterized by no or low alcohol consumption and a high rate of
      attacks of acute pancreatitis. In group 1, PRS turned to more advanced calcified
      stages in 6/16 of patients (37%) followed in 30 to 144 months with a prior stage
      of TC in 2 cases. An evolution toward more calcified stages (TC or ECS) occurred
      in half of the patients belonging to group 2 and 4 in 36 to 84 months. Genetic
      disposition and alcohol consumption could account for the evolution toward more
      calcified stages. A genetic factor is suggested by a rapid evolution to evenly
      calcified stones in two aged children 8 and 10 years and by a high frequency of
      familial cases in patients belonging to groups 2 and 4 (60% and 20%) as compared
      to group 1 with PRS (4%). Alcohol consumption could accelerate the calcifying
      process since patients belonging to groups 2 and 4 had a significantly higher
      alcohol consumption than those with PRS (group 1). CONCLUSION: RPL is a
      heterogeneous pancreatic disease including juvenile and senile presentation which
      may represent about 15% of pancreatic lithiasis. Evolution towards calcified
      stages (PRS then TC then ECS) occurred in 37-50% of cases and could be related to
      a genetic factor and increased alcohol consumption.

PMID- 9262982
TI  - Successful pregnancy in a patient with chronic intestinal pseudo-obstruction
      while on ambulatory percutaneous endoscopic gastrostomy feeding.
AB  - We report a case of ambulatory endoscopic gastrostomy feeding via a low profile
      button device using a portable feeding pump. This provided successful nutritional
      support to a patient with chronic intestinal pseudo-obstruction who became
      pregnant while on gastrostomy feeding. She successfully completed her pregnancy
      with nutritional support through the gastrostomy. The portable feeding pump gave
      her excellent quality of life both indoors and outdoors, and she could continue
      feeding without interrupting her daily housework, shopping and babycare.

PMID- 9262981
TI  - Bile salt-induced cytotoxicity and ursodeoxycholate cytoprotection: in-vitro
      study in perifused rat hepatocytes.
AB  - OBJECTIVES: Membrane toxicity induced by hydrophobic bile salts may be important
      in liver diseases. Administration of ursodeoxycholate reduces serum liver enzymes
      in chronic liver diseases, but the nature of this effect is still unclear. We
      aimed at establishing a convenient in-vitro system for investigating the
      hepatotoxic properties of hydrophobic bile salts and the putative
      hepatoprotective effect of ursodeoxycholate. METHODS: About 100 mg of freshly
      isolated rat hepatocytes were suspended on a resin column (Bio-Gel P4 fine) and
      perifused with different concentrations of bile salts. The effluent was collected
      at 5-min intervals and assayed for lactate dehydrogenase (LDH), aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT) activity. Enzyme
      leakage induced by bile salts was compared with that induced by Triton X-100
      (Union Carbide, Danbury, CT, USA) at different concentrations. After perifusion,
      hepatocytes were collected for electron microscopic observation. RESULTS:
      Cytotoxicity of individual bile salts, assessed by enzyme release, was time and
      concentration dependent and corresponded to their hydrophilic-hydrophobic
      balance. Perifusion with hydrophilic bile salts, cholate and ursodeoxycholate,
      did not result in a significant enzyme release in concentrations up to 5 mmol/l,
      whereas hydrophobic bile salts, chenodeoxycholate and deoxycholate, induced
      significant enzyme leakage even in low concentrations, 0.5 and 0.1 mmol/l,
      respectively. Addition of ursodeoxycholate significantly reduced the hepatotoxic
      effect of deoxycholate. This protective effect was evident within minutes. The
      ultrastructural appearance of hepatocytes exposed to hydrophobic bile salts was
      very similar to the non-specific cellular lysis observed after exposition to
      Triton X-100, suggesting that they act mainly in a detergent-like fashion.
      CONCLUSION: Perifused rat hepatocytes seem a convenient in-vitro system for
      investigating the hepatotoxic properties of bile salts and hepatoprotective
      effect of ursodeoxycholate, offering the opportunity to investigate the effects
      of bile salts under dynamic conditions, mimicking the in-vivo situation, and
      allowing continuous enzyme release monitoring. Hydrophobic bile salts seem to act
      mainly in a detergent-like fashion; ursodeoxycholate-related hepatoprotection
      could be due not only to a dilution effect of toxic bile salts, but also to a
      direct cytoprotective effect.

PMID- 9262983
TI  - Sweet's syndrome: an unusual cutaneous feature of Crohn's disease or ulcerative
      colitis. The South West Gastroenterology Group.
AB  - Sweet's syndrome is characterized by tender, red inflammatory nodules or papules,
      usually affecting the upper limbs, face or neck. It is part of the group of acute
      neutrophilic dermatoses that includes pyoderma gangrenosum, but can be
      distinguished by its appearance, distribution and histological features. Four
      patients with Sweet's syndrome and Crohn's disease are reported. A total of 30
      cases from the literature suggest that Sweet's syndrome is an unusual
      extraintestinal manifestation of either Crohn's disease or ulcerative colitis.
      There is a strong predilection for women (87%), patients with colonic disease
      (100%) and those with other extraintestinal features (77%). The rash is
      associated with active disease in 67-80%, but may precede the onset of intestinal
      symptoms in 21% and has been reported 3 months after proctocolectomy for
      ulcerative colitis.

PMID- 9262985
TI  - Oesophageal lichen planus.
AB  - Lichen planus is a common skin and mucosal disease, with very rare symptomatic
      oesophageal involvement. We report a case of painful dysphagia due to oesophageal
      lichen planus in a 60-year-old woman who also had oral, cutaneous and genital
      lichen planus lesions. Steroid treatment produced considerable improvement of all
      lesions and a rapid symptomatic remission.

PMID- 9262984
TI  - Absence of Epstein-Barr virus (EBV) in a gastrointestinal stromal cell tumour
      (GIST) in an adult human immunodeficiency virus-seropositive patient with past
      EBV infection.
AB  - Gastrointestinal stromal cell tumours (GIST) of the small intestine are rare
      malignancies. Recently, an association of Epstein-Barr virus (EBV) with malignant
      stromal cell tumour in young people with AIDS and past EBV infection has been
      described. We describe a 33-year-old heterosexual male with asymptomatic human
      immunodeficiency virus (HIV) infection who had had an EBV infection in the past
      and who presented with an EBV-negative GIST. The association between EBV and
      malignant stromal cell tumours in young people with AIDS could not be reconfirmed
      in our adult patient. The relationship between EBV and malignant stromal cell
      tumours in AIDS patients and the possible pathogenetic role of EBV remains to be
      established, at least in adults.

PMID- 9262986
TI  - Systemic absorption of 5-aminosalicylic acid in patients with inactive ulcerative
      colitis treated with olsalazine and mesalazine.

PMID- 9262987
TI  - Minimal residual disease detection in B-cell malignancies by assessing IgH
      rearrangement.
AB  - In B-cell malignancies, the uniqueness of the immunoglobulin heavy chain locus
      (IgH) clonal rearrangement provides a useful marker for the detection of minimal
      residual disease (MRD) after treatment. During the last decade, several
      techniques have been proposed and used for detecting MRD. In this review, we
      report the current PCR based techniques dealing with amplification of the VDJ
      segment since the CDR3 region is unique to each IgH rearrangement. The
      sensitivity of these techniques varies considerably with a detection level of one
      tumoral cell in 10(-2) to 10(-6) normal cells. Accurate and sensitive assessment
      of MRD may have profound impact in the clinical management of patients with
      hematologic malignancies. Although, a majority of studies have shown a good
      correlation between the rapidity or extent of the reduction in the number of
      tumoral cells and the subsequent relapse, other studies demonstrated substained
      positivity of PCR in patients in long term remission. Thus, current clinical
      studies of MRD should establish whether MRD predicts relapse uniformly and,
      therefore, justifies intensification of therapy in positive cases, or whether it
      simply detects leukemic cell populations whose proliferative potential has been
      altered by chemotherapy.

PMID- 9262988
TI  - Cytokine-mediated expansion does not deplete cord blood cells with stem cell
      characteristics.
AB  - Cord blood (CB) has been successfully used to regenerate the hematopoietic system
      after myeloablative therapy. We investigated whether cytokine mediated expansion
      depletes CB of cells with stem cell characteristics. CB mononuclear cells (MNC)
      were enriched for quiescent (primitive) stem cells by incubation with 25
      micrograms/ml 5-Fluorouracil (5-FU) and control CB MNC were incubated with media
      alone. Cells were then incubated for 7 days with Interleukin-1 (IL1)+IL3+Stem
      Cell Factor (SCF) and progenitor content, cell cycle status, nucleated cell
      count, immunophenotype and resistance to 25 micrograms/ml 5-FU (primitive stem
      cells) were evaluated before and after cytokine exposure. Incubation with
      IL1+IL3+SCF caused an increase (fold expansion) in committed (28.6 +/- 8.1),
      immature (5.8 +/- 1.8), and primitive progenitors (4.1 +/- 0.8) among control CB
      MNC compared to a decrease in committed progenitors (0 +/- 0) but an increase in
      both immature (8.4 +/- 4.8) and primitive progenitors (7 +/- 2.9) among 5-FU
      resistant CB MNC. An increase in the proportion of CD34+ cells occurred in both
      fractions. Expanded control CB MNC showed a significant increase in numbers of 5
      FU resistant committed (p = 0.024), immature (p = 0.014) and primitive
      progenitors (p = 0.01) as compared with fresh CB MNC. Re-exposure of 5-FU
      resistant expanded CB MNC to 5-FU shows growth of some immature and primitive
      progenitors. Cytokine-mediated expansion of untreated and quiescent CB cells is
      possible and cytokine-mediated expansion does not deplete CB cells with stem cell
      characteristics.

PMID- 9262989
TI  - Incidence of graft vs host disease in allogeneic bone marrow transplantation in a
      single center study from Turkey.
AB  - Graft versus host disease (GVHD) is one of the obstacles encountered in
      allogeneic bone marrow transplantation (alloBMT) and has a direct impact on the
      transplant outcome and survival. In this report, we summarized the incidence of
      acute and chronic GVHD among 71 HLA matched and 9 HLA mismatched sibling alloBMTs
      performed for various hematological malignancies, mainly leukemias seen at Ibn-i
      Sina Hospital. Fifty-five were male and 25 were female Turkish patients. Median
      age was 29 (12-48). Cyclophosphamide(CY)+total body irradiation (TBI)(12),
      CY+total lymphatic irradiation (TLI)(6), busulfan (BU)+CY(58) and ALG/ATG+CY(4)
      were the regimens used for conditioning. Cyclosporin A (CsA)+short term
      methotrexate were given for GVHD prophylaxis except for two syngeneic transplants
      who both received only CsA. In 22 of the patients ABO and in 30 patients sex
      mismatched bone marrow was given. Thirty-one (38.8%) patients showed acute GVHD
      (grade I-II: 22, grade III-IV: 9) and 8 (11.6%) showed chronic GVHD. In HLA
      matched and mismatched patients acute GVHD incidence were 33.7% and 44.4%
      respectively. All of the HLA mismatched patients that showed acute GVHD were in
      advanced stage. Of the patients with acute GVHD, 28 (96.5%) disclosed skin, 22
      (75.9%) hepatic and 14 (48.3%) gut involvement. In the chronic form three
      patients had mild limited, two limited, two moderate and one advanced GVHD. Seven
      of the patients were lost due to GVHD. To determine the graft versus leukemia
      effect of alloBMT, we compared the disease free survival (DFS) of the 68 leukemia
      patients. Although the patients who had grade I-II acute GVHD showed a better DFS
      than the patients who did not have acute GVHD, it did not reach to a significance
      (15.9 vs 13.6 months: p = 0.43).

PMID- 9262990
TI  - Structural and functional studies of hemoglobin Moabit (alpha 86(F7) Leu-->Arg.
AB  - An abnormal hemoglobin fraction was detected on high performance liquid
      chromatography profile performed for the measurement of glycated hemoglobin in a
      55-year-old caucasian patient. The structural and functional studies were
      performed by standard techniques. Separation of hemoglobins by alkaline
      electrophoresis and by IEF revealed a slightly more rapid fraction than does Hb
      S. By acid electrophoresis, no abnormal Hb fraction could be observed. Separation
      of globin chains by electrophoresis demonstrated an alpha-chain variant and by
      chromatography, a fraction which eluted between beta and gamma globin chains.
      Tryptic digests and amino acid analysis have demonstrated a previously described
      substitution of Leu-->Arg alpha 86(F7).

PMID- 9262991
TI  - Expansion of polyclonal B-cell precursors in bone marrow from children treated
      for acute lymphoblastic leukemia.
AB  - In a series of 12 patients (mean age: 3 years at diagnosis) receiving
      chemotherapy for acute lymphoblastic leukemia, bone marrow examinations performed
      during hematopoietic recovery following treatment-induced agranulocytosis or
      completion of maintenance treatment showed at least 15% of non malignant immature
      cells which were sometimes hardly distinguishable from leukemic cells. No
      comparable data was observed in patients treated with G-CSF. The cytological
      features of these cells as well as their immunophenotyping were defined. Results
      showed that the majority of cells expressed HLA-DR, CD19, CD10 and cytoplasmic
      IgM but not the CD34 markers. This predominant and homogeneous pre-B cell
      population which likely represents the expansion of a minor population detectable
      in normal bone marrow is phenotypically indistinguishable from leukemic cells.
      The pattern of IgH gene rearrangements studied by PCR amplification of the CDRIII
      region showed that these cells were polyclonal. Except in one patient, minimal
      residual disease was not detected using probes specific for IgH or TCR gene
      rearrangement of the malignant clone. In children during the hematopoietic
      recovery after chemotherapy, immature marrow cells in great numbers, even with an
      highly homogeneous immunophenotype identical to the malignant clone's, are not
      sufficient for the diagnosis of relapse.

PMID- 9262992
TI  - Evaluation of the ABX Cobas Vega automated hematology analyzer and comparison
      with the Coulter STKS.
AB  - An evaluation of the new automated hematology analyzer was performed in
      comparison with the Coulter STKS on 1,694 blood samples coming from the different
      departments of Nice University Hospital. The Cobas Vega showed very satisfactory
      results in terms of repeatability, reproducibility and linearity. Correlation
      with the STKS was excellent with the exception of the following parameters: red
      blood cell distribution index and the absolute values for eosinophils and
      basophils. Two qualities were particularly appreciable: absence of leukocyte
      carryover, and stability of the complete blood count and leukocyte differential
      count over a long period. Analysis of qualitative flags showed that the overall
      blood smear review rate was 47% for the Cobas Vega, not forgetting that optical
      microscopy detects 37% of all abnormalities. The STKS's review rate was 49.5%.
      Flags commonly concerned the granulocytic lineage, 61% for the STKS and 48% for
      the Vega, with a false positive rate of 43.4% for the STKS compared with 22% for
      the Vega. The opposite phenomenon was observed with the flag for atypical
      lymphocytes which represented 11% of flags for the STKS and 25.6% for the Vega,
      with a false positive rate of 25.5% for the STKS and 34% for the Cobas Vega. This
      may be explained by the fact that lymphocyte abnormalities sometimes generated
      "granulocytic" flags on the STKS. Studies of the false negative rate carried out
      using light microscopy on 505 blood samples without flags on either system,
      detected the presence of a slight myelemia, and a few hyperbasophilic lymphocytes
      or plasmocytes in 18.6% of all cases. Finally, the Cobas Vega's practicality was
      greatly appreciated and there was no trouble with breakdowns throughout the whole
      period of its use.

PMID- 9262993
TI  - Massive delayed hemolysis following peripheral blood stem cell transplantation
      with minor ABO incompatibility.
AB  - After hematopoietic stem cell transplantation, delayed immune hemolysis may occur
      when donor-derived B lymphocytes carried with the graft produce immune antibodies
      against the recipient's incompatible red cells. We report the occurrence of this
      syndrome in the context of minor blood group incompatibility between donor and
      recipient after peripheral blood stem cell (PBSC) transplantation. On day 12 post
      transplant there was abrupt onset of hemolysis necessitating supportive treatment
      with hydration and transfusions. Because, as compared to bone marrow, PBSC grafts
      are enriched with lymphocytes, more frequent and intense delayed immune hemolysis
      may be anticipated when using PBSC. This complication is described most often
      when cyclosporine alone is used for immunosuppression following the graft. The
      addition of methotrexate, which with CyA forms the classic regimen for the
      prevention of graft-vs-host disease, may diminish the frequence and severity of
      this adverse reaction.

PMID- 9262994
TI  - A novel volumetric feature extraction technique with applications to MR images.
AB  - A semiautomated feature extraction algorithm is presented for the extraction and
      measurement of the hippocampus from volumetric magnetic resonance imaging (MRI)
      head scans. This algorithm makes use of elements of both deformable model and
      region growing techniques and allows incorporation of a priori operator knowledge
      of hippocampal location and shape. Experimental results indicate that the
      algorithm is able to estimate hippocampal volume and asymmetry with an accuracy
      which approaches that of laborious manual outlining techniques.

PMID- 9262995
TI  - Multishot rosette trajectories for spectrally selective MR imaging.
AB  - In nuclear magnetic resonance, different spectral components often correspond to
      different chemical species and as such, spectral selectivity can be a valuable
      tool for diagnostic imaging. In the work presented here, a multishot image
      acquisition method based upon rosette K-space trajectories has been developed and
      implemented for spectrally selective magnetic resonance imaging (MRI). Parametric
      forms for the gradient waveforms and design constraints are derived, and an
      example multishot gradient design is presented. The spectral behavior for this
      imaging method is analyzed in a simulation model. For frequencies that are near
      to the resonant frequency, this method results in a lower intensity, but
      undistorted image, while for frequencies that are off-resonance by a large
      amount, the object is incoherently dephased into noise. A method by which
      acquisitions are delayed by small amounts is introduced to further reduce the
      residual intensity for off-resonant signals. An image reconstruction method based
      on convolution gridding, including a correction method for small amounts of
      magnetic field inhomogeneity, is implemented. Finally, the spectral selectivity
      is demonstrated in vivo in a study in which both water and lipid images are
      generated from a single imaging data set.

PMID- 9262996
TI  - Learning-based ventricle detection from cardiac MR and CT images.
AB  - The objective of this work is to investigate the issue of automatically detecting
      regions of interest (ROI's) in medical images. It is assumed that the regions to
      be detected can be roughly segmented by a threshold based on a likelihood measure
      of the ROI. First, an analysis of the global histogram is used to compute a
      preliminary threshold that is likely near the optimal one. The histogram analysis
      is motivated by the analytical result of a bell image intensity model proposed in
      this work. Then, the preliminary threshold is used to segment the input image,
      resulting in an attention map, which contains an attention region that
      approximates the ROI as well as many spurious ones. Due to the nonoptimality of
      the preliminary threshold, it can happen that the attention region contains a
      part of, or more regions than, the ROI. Learning takes place in two stages: 1)
      learning for automatic selection of the preliminary threshold value and 2)
      learning for automatically selecting the ROI from the attention map while
      dynamically tuning the threshold according to the learned-likelihood function.
      Experiments have been conducted to approximately locate the endocardium
      boundaries of the left and right ventricles from gradient-echo magnetic resonance
      (MR) images. Cardiac computed tomography (CT) images have also been used for
      testing. The boundary of the segmented region provided by this algorithm is not
      very accurate and is meant to be used for further fine tuning based on other
      application-specific measures.

PMID- 9262997
TI  - Tracking geometrical descriptors on 3-D deformable surfaces: application to the
      left-ventricular surface of the heart.
AB  - Motion and deformation analysis of the myocardium are of utmost interest in
      cardiac imaging. Part of the, research is devoted to the estimation of the heart
      function by analysis of the shape changes of the left-ventricular endocardial
      surface. However, most clinically used shape-based approaches are often two
      dimensional (2-D) and based on the analysis of the shape at only two cardiac
      instants. Three-dimensional (3-D) approaches generally make restrictive
      hypothesis about the actual endocardium motion to be able to recover a point-to
      point correspondence between two surfaces. The present work is a first step
      toward the automatic spatio-temporal analysis and recognition of deformable
      surfaces. A curvature-based and easily interpretable description of the surfaces
      is derived. Based on this description, shape dynamics is first globally estimated
      through the temporal shape spectra. Second, a regional curvature-based tracking
      approach is proposed assuming a smooth deformation. It combines geometrical and
      spatial information in order to analyze a specific endocardial region. These
      methods are applied both on true 3-D X-ray data and on simulated normal and
      abnormal left ventricles. The results are coherent and easily interpretable.
      Shape dynamics estimations and comparisons between deformable object sequences
      are now possible through these techniques. This promising framework is a suitable
      tool for a complete regional description of deformable surfaces.

PMID- 9262999
TI  - Lesion contrast enhancement in medical ultrasound imaging.
AB  - Methods for improving the contrast-to-noise ratio (CNR) of low-contrast lesions
      in medical ultrasound imaging are described. Differences in the frequency spectra
      and amplitude distributions of the lesion and its surroundings can be used to
      increase the CNR of the lesion relative to the background. Automated graylevel
      mapping is used in combination with a contrast-weighted form of frequency
      diversity speckle reduction. In clinical studies, the techniques have yielded
      mean CNR improvements of 3.2 dB above ordinary frequency-diversity imaging and
      5.6 dB over sharper conventional images, with no post-processing graylevel
      mapping.

PMID- 9262998
TI  - A methodology for specifying PET VOI's using multimodality techniques.
AB  - Volume-of-interest (VOI) extraction for radionuclide and anatomical measurements
      requires correct identification and delineation of the anatomical feature being
      studied. We have developed a toolset for specifying three-dimensional (3-D) VOI's
      on a multislice positron emission tomography (PET) dataset. The software is
      particularly suited for specifying cerebral cortex VOI's which represent a
      particular gyrus or deep brain structure. A registered 3-D magnetic resonance
      image (MRI) dataset is used to provide high-resolution anatomical information,
      both as oblique two-dimensional (2-D) sections and as volume renderings of a
      segmented cortical surface. VOI's are specified indirectly in two dimensions by
      drawing a stack of 2-D regions on the MRI data. The regions are tiled together to
      form closed triangular mesh surface models, which are subsequently transformed
      into the observation space of the PET scanner. Quantification by this method
      allows calculation of radionuclide activity in the VOI's, as well as their
      statistical uncertainties and correlations. The methodology for this type of
      analysis and validation results are presented.

PMID- 9263000
TI  - Choice of initial conditions in the ML reconstruction of fan-beam transmission
      with truncated projection data.
AB  - We investigate the effects of initial conditions in the iterative maximum
      likelihood (ML) reconstruction of fan-beam transmission projection data with
      truncation. In an iterative ML reconstruction, the estimate of the transmission
      reconstructed image in the previous iteration is multiplied by some factors to
      obtain the current estimate. Normally, a flat initial condition (FIC) or an image
      with equal positive pixel values is used as initial condition for an ML
      reconstruction. Usage of FIC has also been perceived as a way of preventing any
      bias on the reconstruction which may have come from the initial condition. When
      projection data have truncation, we show that using an FIC in an ML iterative
      reconstruction can introduce a bias to the reconstruction inside the densely
      sampled region (DSR), whose projection data have no truncation at any angle. To
      reduce this bias, we propose to use the largest right singular vector (LRSV) of
      the system matrix as the initial condition, and demonstrate that the bias can be
      reduced with the LRSV. When data truncation is reduced, the LRSV approaches the
      FIC. This result does not contradict to the use of FIC when projection data are
      not truncated. We also demonstrate that the reconstructed transmission image
      using LRSV as initial condition provides a more accurate attenuation coefficient
      distribution than that using FIC. However, the improvement is mostly in the area
      outside the DSR.

PMID- 9263001
TI  - Development of an intravascular impedance catheter for detection of fatty lesions
      in arteries.
AB  - Recent studies show that the presence of fatty lesions in the atherosclerotic
      vessel wall is a risk factor for acute occlusion of blood vessels. Although fat
      has a high electrical resistivity, existing impedance catheter systems cannot be
      used for detection of these lesions because artifacts owing to impedance
      variations in the extravascular surroundings have a major and irretraceable
      effect on the measurement. Standard algorithms used in attempt to compensate for
      these artifacts suffer from severe instability problems. We defined design
      guidelines to be met by a new impedance catheter system in order to make a robust
      reconstruction algorithm possible and have built an experimental in travascular
      impedance catheter (IIC) system according to these guidelines, using a normalized
      differential measurement procedure. With this IIC, we performed experiments on
      human iliac arteries from the section ward (fixed specimens), showing that
      plastic models of arterial fatty lesions (8 mm3) can be detected reliably.

PMID- 9263002
TI  - Registration of head volume images using implantable fiducial markers.
AB  - In this paper, we describe an extrinsic-point-based, interactive image-guided
      neurosurgical system designed at Vanderbilt University, Nashville, TN, as part of
      a collaborative effort among the Departments of Neurological Surgery, Computer
      Science, and Biomedical Engineering. Multimodal image-to-image (II) and image-to
      physical (IP) registration is accomplished using implantable markers. Physical
      space tracking is accomplished with optical triangulation. We investigate the
      theoretical accuracy of point-based registration using numerical simulations, the
      experimental accuracy of our system using data obtained with a phantom, and the
      clinical accuracy of our system using data acquired in a prospective clinical
      trial by six neurosurgeons at four medical centers from 158 patients undergoing
      craniotomies to resect cerebral lesions. We can determine the position of our
      markers with an error of approximately 0.4 mm in X-ray computed tomography (CT)
      and magnetic resonance (MR) images and 0.3 mm in physical space. The theoretical
      registration error using four such markers distributed around the head in a
      configuration that is clinically practical is approximately 0.5-0.6 mm. The mean
      CT-physical registration error for the phantom experiments is 0.5 mm and for the
      clinical data obtained with rigid head fixation during scanning is 0.7 mm. The
      mean CT-MR registration error for the clinical data obtained without rigid head
      fixation during scanning is 1.4 mm, which is the highest mean error that we
      observed. These theoretical and experimental findings indicate that this system
      is an accurate navigational aid that can provide real-time feedback to the
      surgeon about anatomical structures encountered in the surgical field.

PMID- 9263003
TI  - Identification of the complete expressed human TCR V gamma repertoire by flow
      cytometry.
AB  - Five of the six expressed human TCR V gamma regions (V gamma 2, 3, 4, 8 and 9)
      can be detected by available mAb. No mAb with specificity for the remaining V
      gamma 5 region has been described. In this study, we have characterized mAb 56.3,
      which was obtained after immunization with V gamma 2/3/4/9-negative thymic gamma
      delta cells. V gamma transcripts were analyzed by inverse PCR and RT-PCR in 56.3+
      cell lines and clones derived from peripheral blood. mAb 56.3 recognized all
      cells that expressed in-frame V gamma 5 transcripts. In addition, mAb 56.3
      recognized some but not all cells expressing V gamma 3, but did not react with a
      large panel of clones expressing V gamma 2, 4, 8 or 9. In combination with anti-V
      gamma 2/3/4 mAb 23D12, V gamma 5-expressing cells could be clearly identified as
      56.3+23D12(-). In some donors, mAb 56.3 also recognized a small fraction of TCR
      alpha beta cells. At the clonal level, these cells expressed in-frame V gamma 5-J
      beta-C beta or V gamma 3-J beta-C beta trans-rearrangements. When mAb 56.3 was
      combined with V gamma 2/3/4-, V gamma 8- and V gamma 9-specific mAb, all
      peripheral blood gamma delta T cells were stained. Thus, mAb 56.3 supplements the
      panel of available TCR V gamma-specific mAb. It is now possible to analyze the
      complete expressed human V gamma repertoire by flow cytometry.

PMID- 9263004
TI  - TCR analysis reveals significant repertoire selection during in vitro lymphocyte
      culture.
AB  - The in vitro stimulation of T lymphocytes is frequently used as a technique to
      expand specific cells present at low precursor frequency in vivo. However, cells
      analysed after such procedures may no longer reflect those originally present in
      vivo because of the variable efficiency of outgrowth of different T cell
      subpopulations. To systematically assess this and to complement functional
      assays, we have analysed the TCR repertoire using a new high resolution RT-PCR
      method to determine TCR beta chain CDR3 transcript length. In the ex vivo
      analysis of tumor infiltrating lymphocytes (TIL) of renal cell carcinoma and
      glioblastoma patients, we observed and quantified oligoclonally expanded
      populations of T cells that were very susceptible to repertoire modification upon
      subsequent in vitro culture with autologous tumor cells. This in vitro repertoire
      skewing occurred preferentially with TIL rather than peripheral blood lymphocytes
      and we noted that tumor cells rather than normal cells of the same tissue type
      were the most potent inducers of the effect. It was striking that this selection
      was sometimes negative: certain prominent T cell populations that were highly
      represented in vivo disappeared after in vitro re-stimulation. This suggests that
      the presentation of tumor associated antigens during culture may eliminate rather
      than enrich for in vivo primed T cells. It is clear that in vitro functional
      tests cannot adequately describe all T cells with tumor specificity. Approaches
      that allow the assessment of potentially antigen-reactive T cell populations ex
      vivo are thus an important advance in the global appraisal of anti-tumor T cell
      immune responses.

PMID- 9263005
TI  - Oncogenic mutations in ras create HLA-A2.1 binding peptides but affect their
      extracellular antigen processing.
AB  - Point mutations in oncogene products such as ras may create neoantigenic
      determinants recognizable by T lymphocytes as tumor antigens, that could be
      marshalled to eliminate a tumor by inducing specific cytotoxic T lymphocytes
      (CTL) with an appropriate vaccine. Peptide-pulsed dendritic cells are a promising
      new approach to cancer vaccines. For such an approach to work, the determinant
      must be appropriately processed to the right size fragment and be presented by an
      appropriate HLA molecule. We have investigated both of these issues for a series
      of ras codon 12 and 13 point mutations that contain sequences predicted to bind
      to HLA-A2.1, the most common class I HLA molecule. We find that not only do the
      different mutations affect binding to HLA-A2.1, but also they affect
      extracellular antigen processing in two ways: by influencing the trimming of
      flanking residues from the longer sequence and by influencing the susceptibility
      of the optimal decamer to further proteolytic degradation. The influence of
      internal residues on cleavage of flanking residues downstream demonstrates the
      importance of distant interactions between separated amino acid side chains
      and/or conformational effects in determining antigen processing. These results
      may be important in designing an effective vaccine to induce mutant ras-specific
      tumor immunity.

PMID- 9263006
TI  - B7-CD28 interaction is a late acting co-stimulatory signal for human T cell
      responses.
AB  - The interaction of CD28 with one of the B7 molecules (CD80 and CD86) on
      professional antigen-presenting cells (APC) is generally considered as the most
      important co-stimulatory signal for T cell activation. APC in a resting condition
      express either no or only low levels of B7 molecules. These are up-regulated as a
      result of interactions with activated T cells, thus suggesting that B7-CD28
      interaction is not required at initiation of T cell activation. To study this
      issue, we blocked B7-CD28 interaction at various time points after in vitro
      stimulation of peripheral blood T cells with allogeneic monocytes. Epstein-Barr
      virus-transformed B cells or soluble antigens. We observed that T cell
      proliferation and IL-2 production were inhibited by B7-blocking agents (CTLA-4-Ig
      or anti-B7 mAb) almost to the same degree when added either at initiation of
      culture or 24 h later. B7-blocking agents still resulted in significant
      inhibition of allogeneic T cell activation when added after 48 h. Furthermore,
      when CTLA-4-Ig was added at the start of an allogeneic T cell stimulation,
      addition of anti-CD28 mAb after 24 h of culture nearly fully restored T cell
      proliferation to control levels. Finally, we demonstrate that delayed addition of
      B7-blocking agents together with cyclosporin A 1 day after the onset of culture
      of T cells with allogeneic B cells is highly efficient to induce energy as
      evaluated by lack of proliferation, cytotoxic T lymphocyte reactivity and IFN
      gamma or IL-5 production upon alloantigen rechallenge. Taken together, our data
      can explain why B7 expression on APC is not required at the time of initial APC-T
      cell contact, and suggest that the effect of the CD28 signal indeed consists in
      prolonging IL-2 production and amplifying T cell responses, rather than in
      providing a critical co-stimulatory signal at the time of initial TCR triggering.

PMID- 9263007
TI  - Skewing of TCR V genes to CD4+ and CD8+ subsets of T lymphocytes is not
      determined by amino acid composition of CDR3.
AB  - TCR V genes show differing expression patterns, termed skewing, in CD4+ and CD8+
      subsets of T lymphocytes. To determine which elements of the TCR V regions
      contribute to these observed TCR V gene skewing patterns, we have performed an in
      depth analysis, taking advantage of RT-PCR and DNA sequencing, which was focused
      on the multi-member TCRBV6 gene family. These studies allowed us to evaluate the
      contributions of the various elements, that constitute the TCR beta chain
      variable region, to the observed TCR V gene skewing patterns. The results of
      these analyses revealed that within the TCRBV6 family individual members
      exhibited differing skewing patterns, i.e. TCRB6S7 was significantly skewed
      towards the CD4+ T cell subset, whereas TCRBV6S5 was significantly skewed towards
      the CD8+ subset. Scrutiny of the usage of TCRBV6 family members in combination
      with TCRBJ gene usage and amino acid composition of CDR3 did not reveal obvious
      structural characteristics which would explain the differing skewing patterns
      between TCRBV6S7 and TCRBV6S5. Further examination of these TCR V regions showed
      that the CDR1 and 2 regions within these TCRBV elements were composed of
      different amino acids. These observations suggests that these components
      contribute to the observed TCR V gene skewing patterns.

PMID- 9263008
TI  - Thymus dysfunction and chronic inflammatory disease in gp39 transgenic mice.
AB  - Expression of gp39 on activated T cells provides a co-stimulatory signal in
      peripheral lymphoid tissue that regulates humoral and cell-mediated immunity. The
      function of gp39 and its receptor CD40 in thymus remains uncertain. Here we
      report that overexpression of gp39 in transgenic mouse thymus caused a dose
      dependent decline in thymocyte numbers (> 500 fold), loss of cortical epithelium
      and expansion of CD40+ medullary cells. Transplantation of transgenic bone marrow
      into normal mice indicated that gp39 significantly diminished thymocyte viability
      in the context of a 'normal' thymic environment. The peripheral tissues of
      transgenic mice also accumulated abnormalities in a transgene dose-dependent
      manner that involved inflammation and lymphoid tissue hypertrophy. Animals with
      the highest transgene copy numbers acquired a lethal inflammatory bowel disease
      marked by the infiltration of gp39+ T cells and CD40+ cells into diseased
      tissues. Examination of cells overexpressing gp39 suggested that these defects
      were caused, in part, by the saturation of a mechanism that sequesters gp39
      inside non-activated cells and thus protects the immune system from inappropriate
      gp39-CD40 interaction. These results establish a regulatory role for gp39 in
      thymus function and a causal relationship in mediating chronic inflammatory
      disease.

PMID- 9263010
TI  - Induction of B cell apoptosis by co-cross-linking CD23 and sIg involves aberrant
      regulation of c-myc and is inhibited by bcl-2.
AB  - A novel system to study the effects of co-cross-linking CD23/FceRII and sIg on
      murine B lymphocytes utilizes a highly multivalent form of anti-Ig prepared by
      covalently linking anti-Ig antibodies to a DNP-dextran backbone. CD23-sIg co
      cross-linking is accomplished by the addition of DNP-specific monoclonal IgE.
      Previous studies demonstrated that co-cross-linking CD23 and sIg significantly
      inhibited mouse B cell proliferation, especially at high doses of the multivalent
      anti-Ig. Interestingly, examination of early activation signals reveals no
      difference in B cells subjected to co-cross-linking conditions as compared to B
      cells activated with anti-Ig alone. Total cellular protein tyrosine
      phosphorylation levels are unchanged by co-cross-linking. Analysis of B cell mRNA
      reveals that co-cross-linking the receptors does not alter the expression levels
      of ornithine decarboxylase 8 h after stimulation as compared to the controls. In
      contrast, levels of the proto-oncogene c-myc were significantly elevated 1 h
      after inducing B cell activation under co-cross-linking conditions. However, it
      remains unclear whether this aberrant c-myc regulation plays any role in inducing
      apoptosis. In addition, on day 3 after stimulation, the co-cross-linking of CD23
      and sIg resulted in the formation of apoptotic B cells, determined by both
      photomicroscopy of the B cell cultures and FACS analysis of B cell nuclei. B
      cells obtained from bcl-2 transgenic mice proliferated as well as controls, and
      failed to undergo apoptosis when CD23 and sIg were co-cross-linked on their
      surface. These studies indicate that co-cross-linking of CD23 with B cell sIg
      inhibits B cell proliferation by a mechanism that is distinct from that seen by
      co-cross-linking of the Fc gamma RII and sIg. In addition, these results suggest
      a means by which antigen-specific IgE can down-regulate additional B cell
      activation and IgE synthesis.

PMID- 9263009
TI  - IL-2 and IL-7 differentially induce CD4-CD8- alpha beta TCR+NK1.1+ large granular
      lymphocytes and IL-4-producing cells from CD4-CD8- alpha beta TCR+NK1.1- cells:
      implications for the regulation of Th1- and Th2-type responses.
AB  - Effector functions of CD4-CD8- double negative (DN) alpha beta TCR+ cells were
      examined. Among mouse DN alpha beta TCR+ thymocytes, NK1.1+ cells expressing a
      canonical V alpha 14/J alpha 281 TCR but not NK1.1- cells produce IL-4 upon TCR
      cross-linking and IFN-gamma upon cross-linking of NK1.1 as well as TCR.
      Production of IL-4 but not IFN-gamma from DN alpha beta TCR+NK1.1+ cells was
      markedly suppressed by IL-2. Whereas V alpha 14/J alpha 281 TCR+ cells express
      NK1.1+, these cells are not the precursor of DN alpha beta TCR+NK1.1+CD16+B220+
      large granular lymphocytes (LGL). IL-2 induces rapid proliferation and generation
      of NK1.1+ LGL from DN alpha beta TCR+NK1.1- but not from DN alpha beta TCR+NK1.1+
      cells. LGL cells exhibit NK activity and produce IFN-gamma but not IL-4 upon
      cross-linking of surface TCR or NK1.1 molecules. In contrast to IL-2, IL-7 does
      not induce LGL cells or NK activity from DN alpha beta TCR+NK1.1- cells but
      induces the ability to produce high levels of IL-4 upon TCR cross-linking. Our
      results show that DN alpha beta TCR+ T cells have several distinct
      subpopulations, and that IL-2 and IL-7 differentially regulate the functions of
      DN alpha beta TCR+ T cells by inducing different types of effector cells.

PMID- 9263011
TI  - gp 120s derived from four syncytium-inducing HIV-1 strains induce different
      patterns of CD4 association with lymphocyte surface molecules.
AB  - This work extends our previous finding that lymphocyte treatment with gp120IIIB
      specifically induces CD4 association with several surface molecules to other
      molecules and to three other gp120s from different HIV-1 strains. The ability to
      induce this association was displayed by the four gp120s employed, i.e.
      gp120IIIB, gp120SF2, gp120MN and gp120(451), and the association patterns were
      different, as shown by both co-capping and immunoprecipitation. Co-capping showed
      that all four gp120s significantly potentiated CD4 association with CD3, CD45RA,
      CD45RB, CD38, CD26, CD59 and class I MHC molecules. By contrast, CD4 association
      with CD95 was induced only by gp120(451) and gp120MN; that with CD11a only by
      gp120SF2 and gp120MN; and that with CD27 and CD45RO only by gp120MN and
      gp120(451) respectively. All gp120s induced significant CD4 association with
      CD49d, but gp120SF2 displayed a significantly weaker effect than gp120IIIB.
      Induction of association was not mediated by inside-out signaling via the CD4
      associated tyrosine kinase p58lck, since it was not inhibited by the tyrosine
      kinase inhibitors herbymicin and genistein, nor by CD45 bridging between CD4 and
      the associating molecule, since similar patterns of association were detected IN
      cells expressing different CD45 isoform patterns. Moreover, it was not mediated
      by chemokine receptors interacting with the gp120 V3 loop, since RANTES did not
      alter the gp120-induced CD4 association pattern. By contrast, the observation
      that gp120s from four HIV-1 strains induce different CD4 association patterns
      suggests that gp120 directly interacts with the associating molecules, possibly
      via their hypervariable regions.

PMID- 9263012
TI  - Interplay of J chain and disulfide bonding in assembly of polymeric IgM.
AB  - Normal mouse IgM is synthesized as hexamers in the absence of J chain and as
      pentamers in its presence. Previous work has suggested that polymer size is also
      closely related to formation of the inter-mu chain disulfide bond mediated by
      cysteine 414, one of three cysteines involved in inter-mu chain bonding. This
      correlation in turn suggested that formation of C414-C414 might be required for J
      chain to influence how IgM assembles and that formation of C414-C414 might affect
      the J chain/IgM stoichiometry. To test such hypotheses we have used cell lines
      which either expressed or did not express J chain to produce IgM in which serine
      was substituted for C414. In contrast to the case of IgM assembled from normal mu
      chains, IgM-S414 was secreted mostly as pentamers and tetramers but not as
      hexamers, irrespective of J chain synthesis. These results indicate that the role
      of J chain as modulator of IgM structure and function requires C414. Moreover, a
      more detailed analysis of the structure of J-plus and J-minus IgM-S414 revealed
      that J chain, in fact, influenced the nature of secreted IgM-S414: In the absence
      of J chain, some IgM-S414 was secreted as dimers and trimers, while in the
      presence of J chain, some IgM was secreted as non-covalently assembled pentamers.
      These results imply that disulfide bonding can occur differently from the pattern
      depicted in conventional models of IgM structure.

PMID- 9263013
TI  - Direct evidence for the contribution of B cells to the progression of insulitis
      and the development of diabetes in non-obese diabetic mice.
AB  - The non-obese diabetic (NOD) mouse is an excellent animal model of autoimmune
      diabetes associated with insulitis. The progression of insulitis causes the
      destruction of pancreatic beta cells, resulting in the development of
      hyperglycemia. Although it has been well documented that T cells are required for
      the development of insulitis and diabetes in NOD mice, the importance of B cells
      remains unclear. To clarify the role of B cells in the pathogenesis of NOD mice,
      we therefore generated B cell-deficient NOD (B-NOD) mice. Surprisingly, none (of
      13) of the B-NOD mice developed diabetes by 40 weeks of age, while the control
      littermates with B cells (B+NOD) suffered from a high proportion (43 of 49) of
      diabetes. The insulin reactivity of B+NOD mice was significantly impaired, while
      the B-NOD mice showed a good insulin response, thus suggesting the pancreatic
      beta cell function to be well preserved in B-NOD mice. Although B-NOD mice did
      develop insulitis, the extent of insulitis was significantly suppressed. These
      data thus provide the direct evidence that B cells are essential for the
      progression of insulitis and the development of diabetes in NOD mice.

PMID- 9263014
TI  - Characterization of the specificity and duration of T cell tolerance to
      intranasally administered peptides in mice: a role for intramolecular epitope
      suppression.
AB  - Mucosal administration of antigens in experimental animals leads to the induction
      of peripheral T cell tolerance. We have previously reported that in H-2b mice,
      intranasal (i.n.) or oral administration of a peptide containing the
      immunodominant T cell epitope will down-regulate the function of CD4+ T cells
      reactive with Der P 1, a major target antigen in both B and T cell responses to
      house dust mite. In the present study we have investigated the tolerogenicity of
      peptides containing both dominant and subdominant determinants when given i.n. to
      nalve mice. Induction of tolerance by the nasally administered immunodominant
      peptide leads to a diminution in all T cell-derived cytokines and modulation of
      delayed-type hypersensitivity responses, but IgE production did not seem to be
      affected, furthermore the induction of T cell tolerance was stable, lasting
      beyond 6 months. We have also examined the specificity of intramolecular epitope
      suppression which is a feature of mucosal tolerance induced by nasally
      administered peptides and demonstrate that regulatory CD4+ T cells may exert
      their suppressive effect by linked recognition of epitopes on the same or
      neighbouring antigen-presenting cells.

PMID- 9263015
TI  - Analysis of antibody reactivities toward self antigens of IgM of patients with
      Waldenstrom's macroglobulinemia.
AB  - By using a quantitative immunoblotting technique, we have analyzed the
      repertoires of antibody reactivities of IgM directed toward self antigens in the
      serum of patients with Waldenstrom's macroglobulinemia (WM) and in the serum of
      healthy adults. Monoclonal IgM of patients with WM expressed various degrees of
      polyreactivity and a high degree of heterogeneity with regard to the number and
      the nature of the protein bands that were recognized in homologous tissue
      extracts. Heterogeneous patterns of reactivity of WM IgM contrasted with the
      conserved profiles of reactivity of IgM in the serum of healthy blood donors.
      Protein bands that were recognized by WM IgM belonged to the restricted set of
      self antigens recognized in homologous tissues by normal polyclonal IgM,
      indicating the absence of a disease-specific reactivity profile of monoclonal WM
      IgM. Thus, monoclonal IgM that is present in large amounts in WM distorts the
      homogeneous pattern of reactivity of natural antibodies with self antigens which
      characterizes the natural antibody repertoire of healthy individuals.

PMID- 9263016
TI  - A novel first primary anchor extends the MHC class II I-Ad binding motif to
      encompass nine amino acids.
AB  - The MHC class II molecule I-Ad has been reported to bind peptides containing a
      motif of six consecutive amino acids. We demonstrate that binding of the murine
      IgG2ab heavy chain allopeptide gamma 2ab 435-451 (Kabat numbering) to I-Ad is
      strongly enhanced by a novel first primary anchor (P1) three residues N-terminal
      to this hexamer. This is based on flow cytometric assessment of the I-Ad binding
      capacity of gamma 2ab peptide analogues, their antigenicity for I-Ad-restricted T
      cell clones and molecular modelling. The P1 pocket is broadly specific since
      allphatic, aromatic, acidic, the basic histidine and small polar side chains all
      allowed good binding. By contrast, asparagine, arginine and glycine reduced the
      binding capacity 10-, 16- and > 100-fold respectively. Truncation or glycine
      substitution at P1 decreased antigenicity by a factor > 1000. Nevertheless, I-Ad
      restricted T cells are not completely dependent on this anchor since high
      concentrations of a peptide with glycine-substituted P1 elicited maximal
      responses. Additional anchoring side chains are found at P4, P6 and P9. The
      autologous IgG2aa heavy chain shares prominent epitopic residues with gamma 2ab
      435-451 at P3, P5 and P8. However, the lysine of gamma 2aa at P9 impairs binding
      to I-Ad, which may explain why the gamma 2ab allopeptide-reactive T cells escaped
      negative selection. The data rationalize our observation (Bartnes, K. and
      Hannestad, K. 1997. Eur. J. Immunol. 27:1124) that these T cells recognize a
      syngeneic B cell lymphoma, provided its presentation of intrinsic gamma 2aa is
      enhanced by surface IgG2aa ligation.

PMID- 9263017
TI  - Diversity of epitopes recognized by cytotoxic T lymphocytes that are specific for
      rejection antigen peptide pRL1a presented on BALB/c leukemia RL Male 1.
AB  - Cytotoxic T lymphocytes (CTL) generated in (BALB/c x C57BL/6)F1 (CB6F1) and
      BALB/c spleen cells stimulated with BALB/c radiation-leukemia RL Male 1 cells or
      pRL1a (IPGLPLSL) peptide itself recognized pRL1a on RL Male 1 in association with
      Ld. We first studied pRL1a peptide residues used for binding to the Ld molecule
      by examining the inhibition by variant peptides with single Ala substitutions at
      each position (P) of recognition of P815 target cells sensitized with Ld-binding
      p2Ca (LSPFPFDL) peptide for BALB/c anti-p2Ca CTL. The results showed that Leu at
      P8 is predominantly involved in the binding and Pro at P2 is partially involved.
      Substitution of Gly to Ala at P3 increased binding. We then investigated the
      epitope residues recognized by four pRL1a-specific CTL clones by examining their
      cytotoxicity against the P815 target sensitized with variant pRL1a peptides.
      Recognition by clone Y-16 involved predominantly Leu at P4 and P6, and also Pro
      at P5 and Ser at P7, and partially Ile at P1. Recognition by clone U-41 involved
      predominantly Ile at P1 and Leu at P6, and partially Gly at P3, Leu at P4, Pro at
      P5 and Ser at P7. Recognition by clone P-2 involved predominantly Leu at P4 and
      P6, and Ser at P7, with no partial involvement of other substitutions being
      observed. Finally, recognition by clone B-24 predominantly involved all residues,
      except Gly at P3, which was partially involved. TCR V beta genes utilized by
      those CTL clones were different. The findings show that tumor antigen peptide
      pRL1a generates a wide repertoire of CTL clones that differ in TCR V beta usage
      and in the intrapeptide epitope residues they recognize.

PMID- 9263018
TI  - DNA vaccination with plasmids encoding the intracellular (HBcAg) or secreted
      (HBeAg) form of the core protein of hepatitis B virus primes T cell responses to
      two overlapping Kb- and Kd-restricted epitopes.
AB  - Plasmid DNA encoding either the intracellular form HBcAg or the secreted form
      HBeAg of the core protein of hepatitis B virus (HBV) was injected into the muscle
      of H-2b, H-2d or F1b x d mice. Serum antibody responses and class I-restricted
      cytotoxic T lymphocyte (CTL) responses to HBcAg/ HBeAg were detected in all mice
      tested. Stable murine H-2b and H-2d transfectants that express either
      intracellular HBcAg were secreted HBeAg were constructed. With these cell lines
      we restimulated in vitro T cells primed in vivo and detected their specific
      cytolytic reactivity against naturally processed peptides. CD8+ CTL responses
      elicited by DNA vaccination with plasmids encoding HBcAg or HBeAg were specific
      for the (previously described) Kd-binding HBcAg93-100 peptide MGLKFRQL in H-2b
      mice or the (newly defined) Kd-binding HBcAg87-96 peptide SYVNTNMGL in H-2d mice.
      The overlapping epitopes span residues 87-100 of HBcAg, and are present on HBcAg
      and HBeAg. CTL responses were equally well elicited in vivo by injecting HBcAg-
      or HBeAg-expressing plasmid DNA, and CTL efficiently recognize in vitro HBcAg-
      and HBeAg-expressing transfectants. DNA vaccination of F1b x d mice with HBcAg-
      or HBeAg-expressing plasmid DNA primed CTL populations that recognized the Kb- or
      the Kd-restricted epitope. Both Kb- and Kd-binding peptides are thus generated
      from cytoplasmic/nuclear HBcAg and secreted HBeAg. These data make it unlikely
      that the appearance of HBeAg-negative variants during chronic HBV infection
      results from CTL-driven selection. DNA vaccination is an efficient technique to
      prime CTL responses against overlapping epitopes present on intracellular or
      secreted viral protein antigens.

PMID- 9263019
TI  - Expression of the H2-E molecule mediates protection to collagen-induced arthritis
      in HLA-DQ8 transgenic mice: role of cytokines.
AB  - Transgenic mice expressing DQA1*0301 and DQB1*0302 (HLA-DQ8) molecules in class
      II-deficient Ab degree mice are susceptible to collagen-induced arthritis (CIA).
      To evaluate the role of the H2-E molecule (a homolog of HLA-DR) in DQ-restricted
      arthritis, the H2-E gene was introduced into DQ8.Ab degree mice to generate
      DQ8/E+.Ab degree mice. Expression of the E molecule protects DQ8.Ab degree mice
      against arthritis. In vitro studies using draining lymph nodes from mice primed
      with bovine type II collagen (BII) showed that the response to BII in both
      transgenics is DQ and CD4 restricted. Challenge with BII in vitro leads to
      production of high levels of IFN-gamma in DQ8 and IL-4 in DQ8/E+ mice. We have
      hypothesized that the H2-E molecule modulates the T cell repertoire and changes
      the cytokine balance, resulting in protection of disease.

PMID- 9263020
TI  - Further evidence for supporting cell conversion in the damaged avian basilar
      papilla.
AB  - Two lines of evidence suggested that a process other than supporting cell
      divisions may give rise to new hair cells in the bird inner ear injured by either
      noise or ototoxic drugs. This process, supporting cell conversion, occurs when
      non-dividing supporting cells transdifferentiate into hair cells. First, noise
      exposed chicks received zero, one or two daily i.p. injections of cytosine
      arabinoside (a DNA synthesis blocker), as well as two daily intraperitoneal
      injections of bromodeoxyuridine, for four days. Following sacrifice, the papillae
      were processed for bromodeoxyuridine immunocytochemistry. All the ears
      demonstrated dividing cells, but increasing the number of cytosine arabinoside
      injections decreased the number of labeled cells. Indeed, two cytosine
      arabinoside injections per day nearly completely blocked supporting cell
      divisions in the short hair cell region within the sound-induced lesion. This
      suggested that unpaired, immature cells observed in a similar region with
      scanning electron microscopy, despite the presence of cytosine arabinoside, may
      have been products of supporting cell conversion. In the second experiment, birds
      were treated with gentamicin for three days. Upon sacrifice at 6 days post
      treatment, papillae were processed for light and transmission electron
      microscopy. Several unusual cells were observed with phenotypic features of both
      hair cells and supporting cells. The peculiar cells may be in a transition from
      the supporting cell phenotype to that of a hair cell.

PMID- 9263021
TI  - Ionic currents in regenerating avian vestibular hair cells.
AB  - By applying the conventional whole-cell patch-clamp technique in combination with
      the slice procedure, we have investigated the properties of avian semicircular
      canal hair cells in situ. Passive and active electrical properties of hair cells
      from control animals have been compared with those of regenerating hair cells
      following streptomycin treatment (that killed almost all hair cells).
      Regenerating type II hair cells showed patterns of responses qualitatively
      similar to those of normal hair cells. However, parameters reflecting the total
      number of ionic channels and the surface area of type II hair cells changed
      during recovery-suggesting that new hair cells came from smaller precursors which
      (with time) reacquired the same electrophysiological properties as normal hair
      cells. Finally, we have investigated the ionic properties of a small sample of
      type 1 hair cells. Ionic currents of regenerating type I hair cells did not show,
      at least in the temporal window considered (up to 10 weeks from the end of the
      streptomycin treatment), the typical ionic currents of normal type I hair cells,
      but expressed instead ionic currents resembling those of type II hair cells. The
      possibility that regenerating type I hair cells can transdifferentiate from type
      II hair cells is therefore suggested.

PMID- 9263022
TI  - Discharge properties of pigeon single auditory nerve fibers after recovery from
      severe acoustic trauma.
AB  - The time course of recovery of compound action potential (CAP) thresholds was
      observed in individual adult pigeons after severe acoustic trauma. Each bird had
      electrodes implanted on the round window of both ears. One ear was exposed to a
      tone of 0.7 kHz at 136-142 dB SPL for 1 hr under general anesthesia. Recovery of
      CAP audiograms was monitored twice a week after trauma. Single unit recordings
      from auditory nerve fibers were made after 3 weeks and after 4 or more months of
      the exposure. The CAP was abolished immediately after overstimulation in all
      animals. Based on the temporal patterns of functional recovery of the CAP three
      groups of animals were identified. The first group was characterized by fast
      functional recovery starting immediately after trauma followed by a return to pre
      exposure values within 3 weeks. In the second group, slow functional recovery of
      threshold started 1-2 weeks after trauma followed by a return to pre-exposure
      values by 4-5 weeks. A mean residual hearing loss of 26.3 dB at 2 kHz remained.
      The third group consisted of animals that did not recover after trauma. Three
      weeks after the exposure, tuning curves of single auditory nerve fibers were very
      broad and sometimes irregular in shape. Their thresholds hovered around 120 dB
      SPL. Spontaneous firing rate and driven rate were much reduced. Four or more
      months after exposure, the thresholds and sharpness of tuning of many single
      units were almost completely recovered. Spontaneous firing rate and driven rate
      were comparable to those of control animals. In the slow recovery group neuronal
      tuning properties showed less recovery, especially at frequencies above the
      exposure frequency. Thresholds and sharpness of tuning were normal at frequencies
      below the exposure frequency, but were much poorer at frequencies above the
      exposure. Spontaneous firing rate was much reduced in fibers with high
      characteristic frequencies. In fast recovering animals, the papilla was
      repopulated with hair cells after 4 months. In slow recovering animals, short
      (abneural) hair cells were still missing over large parts of the papilla after 4
      months of recovery. Residual short (abneural) hair cell loss was largest at two
      areas, one more basal and the other more apical to the characteristic place of
      the traumatizing frequency. The results show that, in adult birds, functional
      recovery from severe damage to both short (abneural) and tall (neural) hair cells
      occurs. However, the onset of recovery is delayed and the time course is slower
      than after destruction of short (abneural) hair cells alone. Also, recovery is
      incomplete, both functionally and morphologically. There is residual permanent
      hearing loss, and regeneration of short (abneural) hair cells is incomplete.

PMID- 9263024
TI  - Morphological evidence for supporting cell to hair cell conversion in the
      mammalian utricular macula.
AB  - The possible origin of the immature hair cells that appear in the utricular
      maculae of guinea pigs following gentamicin-induced hair cell death was
      investigated. Guinea pigs were continuously infused with bromodeoxyuridine, to
      label proliferating cells and their progeny, for 2 weeks after inducing damage to
      the inner ear on one side with gentamicin. The opposite ear in each animal served
      as control. Serial sections were cut through the entire utricular maculae of both
      ears of each animal and the number of labelled cells in the epithelium and
      underlying connective tissue was counted. Label was present in cells in the
      sensory epithelium in the utricles from the drug exposed ears but not in the
      controls. The nuclei of cells in the underlying connective tissue were also
      labelled in both ears. Some of the labelled nuclei in the epithelium were at the
      level normally occupied by hair cells, but most were at the level of supporting
      cell nuclei. However, the total number of labelled nuclei in the sensory
      epithelium was small; the maximum was 12 in one animal. The number of labelled
      nuclei in the connective tissue of the treated ears was significantly greater
      than the number in the untreated ear. This confirms that cell proliferation is
      stimulated in the mature mammalian utricular macula after hair cell loss, but the
      extent to which it occurs appears to be insufficient to explain the recovery in
      hair cell numbers which is observed. Detailed thin section studies of the
      utricular maculae of gentamicin-treated animals over a prolonged post-treatment
      period were also performed. In utricles which had suffered damage, there were
      cells which, like supporting cells but unlike hair cells, were resting on
      basement membrane, but which possessed at their apical ends organized bundles of
      microvilli similar to immature hair cell stereocilia. Other cells with more
      obvious stereocilia remained in contact with the basement membrane via and a
      small feet process. In still other cells, where a stereociliary bundle was
      obvious and almost mature in appearance, there was a foot process extending
      towards the basement membrane but not quite in contact, suggesting it had just
      detached. All these cells were contacted by nerve endings and specialization of
      the membranes were apparent at the site of cell-neurone contact. The
      morphological characteristics of these cells are consistent with phenotypic
      conversion of supporting cells into hair cells and this may account for some of
      the hair cell production in the mature mammalian vestibular sensory epithelia
      after hair cell death.

PMID- 9263023
TI  - Calbindin and parvalbumin are early markers of non-mitotically regenerating hair
      cells in the bullfrog vestibular otolith organs.
AB  - Earlier studies have demonstrated hair cell regeneration in the absence of cell
      proliferation, and suggested that supporting cells could phenotypically convert
      into hair cells following hair cell loss. Because calcium-binding proteins are
      involved in gene up-regulation, cell growth, and cell differentiation, we wished
      to determine if these proteins were up-regulated in scar formations and
      regenerating hair cells following gentamicin treatment. Calbindin and parvalbumin
      immunolabeling was examined in control or gentamicin-treated (GT) bullfrog
      saccular and utricular explants cultured for 3 days in amphibian culture medium
      or amphibian culture medium supplemented with aphidicolin, a blocker of nuclear
      DNA replication in eukaryotic cells. In control cultures, calbindin and
      parvalbumin immunolabeled the hair bundles and, less intensely, the cell bodies
      of mature hair cells. In GT or mitotically-blocked GT (MBGT) cultures, calbindin
      and parvalbumin immunolabeling was also seen in the hair bundles, cuticular
      plates, and cell bodies of hair cells with immature hair bundles. Thus, these
      antigens were useful markers for both normal and regenerating hair cells.
      Supporting cell immunolabeling was not seen in control cultures nor in the
      majority of supporting cells in GT cultures. In MBGT cultures, calbindin and
      parvalbumin immunolabeling was up-regulated in the cytosol of single supporting
      cells participating in scar formations and in supporting cells with hair cell
      like characteristics. These data provide further evidence that non-mitotic hair
      cell regeneration in cultures can be accomplished by the conversion of supporting
      cells into hair cells.

PMID- 9263025
TI  - Quantification of the process of hair cell loss and recovery in the chinchilla
      crista ampullaris after gentamicin treatment.
AB  - The degree of ototoxic drug sensitivity and hair cell repair was determined in
      the chinchilla horizontal crista ampullaris after intraotic administration of
      gentamicin. Histological evaluation was made of 22 cristae ampullaris from one
      normal and six post-treatment (PT) animal groups killed at 1, 4, 7, 14, 28, and
      56 days. New hair cell production was quantified, using the dissector technique.
      Transmission electron microscopy was used to investigate the ultrastructural
      characteristics of the hair cells in the regenerated epithelium. At 1 day PT,
      type I and II hair cells presented cytoplasmic vacuolization, swollen nerve
      calyces and 20% of type I and 18% of type II hair cells were lost. At 4 days PT,
      95% of type I hair cells and 14% of type II hair cells had disappeared. In
      addition, most of the type II hair cells showed clumping of nuclear material.
      Nerve fibers were not found in the sensory epithelium, but were still observed
      below the basal lamina. Supporting cells appeared unaffected, maintaining their
      location in the crista. At 1 and 4 days PT, the damage to hair cells was more
      pronounced in the central region of the crista ampullaris. The degree of ototoxic
      damage at 7 days was similar to that of 14 days: no type I hair cells were
      present and most of the type II hair cells had disappeared; supporting cell
      nuclei began to occupy the apical part of the sensory epithelium and most of the
      nerve fibers had retracted. Quantitatively, 87 and 93% of type II hair cells were
      lost at 7 and 14 days PT, respectively. Initial signs of hair cell recovery began
      at 28 days PT; immature type II-like hair cells appeared, supporting cell nuclei
      began to align at the base of the sensory epithelium and nerve fibers penetrating
      the basal lamina were observed. No type I hair cells were found, but 40% of the
      normal number of type II hair cells were present. Hair cells appeared to
      regenerate in the peripheral areas of the cristae ampullaris first. At 56 days
      PT, an increase in the number of mature type II hair cells was present,
      supporting cells were aligned at the base of the epithelium, and more nerve
      fibers appeared to penetrate the basal lamina to the sensory epithelium. Although
      type I hair cells were absent from the epithelium 55% of the normal number of
      type II hair cells were present. At this time, more regenerated hair cells were
      located in the center of the cristae ampullaris as compared to the periphery. At
      the transmission electron microscopic level, type II hair cells at different
      stages of maturation were observed. Some exhibited mature stereocilia, a
      cuticular plate, and terminal endings with synaptic specialization opposing these
      hair cells. In conclusion, type I hair cells were more sensitive than type II
      hair cells to gentamicin intoxication (as they disappeared as early as 4 days
      PT). After 56 days PT, the number of type II hair cells reached 55% of normal. No
      type I hair cells had regenerated at this time. These results demonstrate
      quantitatively the differential ototoxic sensitivity and regenerative capacity of
      hair cells.

PMID- 9263026
TI  - Cellular interactions as a response to injury in the organ of Corti in culture.
AB  - We discovered and described ultrastructurally the intricate relationships between
      the sensory cells and their supporting cells in cultures of the organ of Corti
      following laser beam irradiation. Injury was performed using a 440 nm nitrogen
      dye pulse laser aimed at the cuticular plates of inner hair cells. Laser injury
      is compared with mechanical injury inflicted on the hair cell region by a pulled
      glass pipette. Regardless of the type of injury, but depending on its severity,
      the surviving hair cells may: (1) lose their stereocilia but subsist at the
      surface of the organ; (2) retain contact with the reticular lamina but be
      overgrown by the processes of the supporting cells; or (3) become sequestered
      from the reticular lamina and internalized among the supporting cells, where they
      either remain dedifferentiated or regrow an apical process which regains contact
      with the surface of the organ. All supporting cells, including pillar and Deiters
      cells take part in wrapping their respective inner or outer hair cells. The
      supporting cells not only cover the injured sensory cells, but also invert their
      villi toward the maimed cuticular plates and release an extracellular matrix
      around them. We suggest that the supporting cells play a protective and trophic
      role in the recovery of injured hair cells.

PMID- 9263027
TI  - Does the organ of Corti attempt to differentiate new hair cells after antibiotic
      intoxication in rat pups?
AB  - In the adult mammalian cochlea, post-injury hair cell losses are considered to be
      irreversible. Recent studies in cochlear explants of embryonic rodents show that
      the organ of Corti can replace lost hair cells after injury. We have investigated
      this topic in vivo during the period of cochlear development. Rat pups were
      treated with a daily subcutaneous injection of 500 mg/kg amikacin for eight
      consecutive days between postnatal day 9 (PND 9) and PND 16. During this period
      the organ of Corti is not fully mature, but hair cells are hyper-sensitive to
      aminoglycoside antibiotics. Scanning and transmission electron microscopy was
      used to evaluate morphological changes in the organs of Corti during the
      treatment and at different post-treatment periods, up until PND 90. A massive
      loss in outer and inner hair cells was observed at least as early as PND 14. A
      prominent feature in the apical part of cochleas at PND 21 and 35 was the
      transient presence of small atypical cells in the region of pre-existing outer
      hair cells. These atypical cells had tufts of microvilli reminiscent of nascent
      stereociliary bundles. A second striking observation was the replacement of
      degenerating inner hair cells by pear-shaped supporting cells throughout the
      cochlea. These cells were covered with long microvilli, and their basal pole was
      contacted by both afferent and efferent fibers, as in the early stages of inner
      hair cell maturation. At PND 55 and 90, these features were not clearly observed
      due to further cytological changes in the organ of Corti. It is possible that an
      attempt at hair cell neodifferentiation could occur in vivo after an amikacin
      treatment in the rat during the period of cochlear hyper-sensitivity to
      antibiotic.

PMID- 9263028
TI  - Factors modulating supernumerary hair cell production in the postnatal rat
      cochlea in vitro.
AB  - It has been shown in the past that extra hair cells or supernumerary cells can be
      produced when neonatal cochleae are maintained in vitro. In this report, we
      investigated the effects of the culture methods, molecules and growth factors
      that are thought to be involved in cell proliferation. Quantitative studies of
      supernumerary hair cells were made by measuring the cell density over the entire
      spiral lamina at two postnatal stages: birth and 3 days after birth. With a
      standard feeding solution without serum, a difference in cell density was
      observed between the two methods of culture. Cochlear explants in a standard
      feeding solution supplemented with serum showed an increase of cell density only
      when the explantation is made at birth. Retinoic acid added to the standard
      feeding solution did not increase the hair cell density, while insulin induced an
      increase, especially at 5 micrograms/ml. Several growth factors were tested.
      Epidermal growth factor (EGF) presented a dose dependent effect with an increase
      of up to 30% of hair cell density that was observed in the basal region when the
      explantation was made at birth. Transforming growth factor-alpha did not induce
      an increase of cell density, whereas transforming growth factor-beta presented an
      effect on hair cell density, with a dose dependent effect reaching 37.4% for the
      basal inner hair cells. Interpretation of these results is limited because of the
      lack of data concerning the presence of specific membrane receptors. One
      possibility is that insulin stimulates hair cell differentiation from existing
      undifferentiated cells. Another hypothesis may be related to the EGF and
      transforming growth factor-beta, where these molecules might induce
      transdifferentiation of cells by acting on the transmembrane molecules and the
      extracellular matrix.

PMID- 9263029
TI  - The development of the reticular lamina in the hamster: an examination of
      transitory features and their functional roles.
AB  - This study examines the development of the reticular lamina in the Syrian golden
      hamster postriatally from birth to adulthood at 2 day intervals using the
      scanning electron microscope. During this period, numerous transitory features
      emerged whose roles were concerned primarily with the development of the
      tectorial membrane (TM). The principal findings were as follows. (1) The surface
      of the developing organ of Corti produced all the fibrous material composing the
      minor tectorial membrane (mTM) including radial and longitudinal fiber bundles
      which formed the skeleton of the TM, and spongy, amorphous material which formed
      its intervening ground substance. (2) Throughout most of the cochlear spiral,
      radial fiber bundles were seen extending from the microvilli of supporting cells
      and projecting toward the major tectorial membrane (MTM). In most of the basal
      turn, but not in the apical turn, these radial bundles were interwoven with
      longitudinal fiber bundles which emerged from the surface of Hensen's cells.
      These findings indicate that the architecture of the TM is more complex in the
      basal turn than in the apex. (3) Increases in the dimensions of the reticular
      lamina resulted from the emergence of pillar cell headplates and growth in the
      diameter of hair cells and supporting cells. The emergence of pillar cell
      headplates was the principal factor contributing to increases in the radial
      dimension of the reticular lamina. This emergence was most dramatic between 10
      and 12 days after birth (DAB) after the mTM completed its growth. Since the mTM
      appears to be bound medially to the MTM and laterally to the marginal pillars by
      10 DAB, it seems likely that the growth of the reticular lamina after 10 DAB
      causes some stretching of the mTM both radially and longitudinally. (4)
      Completion of outer hair cell stereocilia growth at 8 DAB was followed by loss of
      supporting cell attachments of the TM (trabeculae) by 10 DAB, and coincided with
      the formation of marginal pillars from the third row of supporting cells. It is
      suggested that the formation of marginal pillars may be required for coupling of
      the TM to the tips of outer hair cell stereocilia and for induction of radial
      tension of the mTM. (5) Removal of the marginal pillar attachments occurred
      following completion of hair cell growth. (6) All structures on the reticular
      lamina appeared to have adult-like characteristics by 20 DAB.

PMID- 9263030
TI  - Immortalized cell lines from embryonic avian and murine otocysts: tools for
      molecular studies of the developing inner ear.
AB  - Recently, our studies have focused on genes expressed at the earliest stages of
      inner ear development. Our aim is to identify and characterize genes that are
      involved in determining the axes of the semicircular canals, in otic crest
      delamination and in early innervation of the inner ear. Many elegant studies of
      auditory development have been done in animal models. However, the need for large
      amounts of well-characterized embryonic material for molecular studies makes the
      development of otocyst cell lines with different genetic repertoires attractive.
      We have therefore derived immortalized otocyst cells from two of the most widely
      used animal models of ear development: avians and mice. Avian cell isolates were
      produced from quail otocysts (embryonic stage 19) that were transformed with
      temperature-sensitive variants of the Rous sarcoma virus (RSV). Among the
      individual transformed cells are those that produce neuron-like derivatives in
      response to treatment with 10(-9) M retinoic acid. Mammalian cell isolates were
      derived from otocysts, of 9 day (post coitus) embryos of the H2kbtsA58 transgenic
      mouse (Immortomouse), which carries a temperature-sensitive variant of the Simian
      Virus 40 Tumor antigen. The vast majority of cells of the Immortomouse are
      capable of being immortalized at 33 degrees C, the permissive temperature for
      transgene expression, in the presence of gamma-interferon. Several putative
      clones et these cells differentiated into neuron-like cells after temperature
      shift and withdrawal of gamma-interferon; another isolate of cells assumed a
      neuron-like morphology on exposure to brain-derived neurotrophic factor even at
      the permissive temperature. We describe also a cell isolate that expresses the
      Pax-2 protein product and two putative cell lines that express the protein
      product of the chicken equivalent of the Drosophila segmentation gene engrailed.
      These genes and their protein products are expressed in specific subpopulation of
      otocyst cells at early stages. Both mouse and quail immortalized cell lines will
      be used to study inner ear development at the molecular level.

PMID- 9263031
TI  - Conditional immortalization of hair cells from the inner ear.
AB  - The aim of this work was to culture conditionally immortalized cells that possess
      the potential to differentiate into mechanosensory hair cells. Utricular
      epithelia at embryonic stage E16 were cultured from the vestibular system of the
      H2kbtsA58 transgenic mouse (Immortomouse) that carries a conditionally expressed
      immortalizing gene derived from the simian virus 40. Immunolabelling showed that
      the immortalizing transgene product, the T antigen (Tag), was expressed in
      utricular cells under permissive conditions and that it was inactivated under non
      permissive conditions. Several morphologically distinct cell types proliferated
      when Tag was expressed, including those that resembled fibroblasts, nerve cells
      and epithelial cells. Mixed cultures of cells from the utricle, passaged up to 50
      times every 3-4 days over a period of 5 months, were subsequently allowed to
      differentiate for 10 days by transferring them to non-permissive conditions.
      Monoclonal antibody markers were used to locate expression of hair cell specific
      antigens. One antibody that normally labels stereociliary bundles from postnatal
      stage P4-6 labelled cellular projections from a population of spheroid cells that
      were distributed across the culture surface. A second antibody that normally
      labels stereociliary bundles did not label the same structures. We conclude that
      utricular hair cell progenitors can be derived from the H2kbtsA58 transgenic
      mouse but that under the experimental conditions used they do not follow the
      normal pattern of differentiation.

PMID- 9263032
TI  - Transforming growth factor alpha treatment alters intracellular calcium levels in
      hair cells and protects them from ototoxic damage in vitro.
AB  - To determine if transforming growth factor alpha (TGF alpha) pretreatment
      protects hair cells from aminoglycoside induced injury by modifying their
      intracellular calcium concentration, we assayed hair cell calcium levels in organ
      of Corti explants both before and after aminoglycoside (i.e. neomycin, 10(-3) M)
      exposure either with or without growth factor pretreatment. After TGF alpha (500
      ng/ml) treatment, the intracellular calcium level of hair cells showed a five
      fold increase as compared to the levels observed in the hair cells of control
      cultures. After ototoxin exposure, calcium levels in hair cells of control
      explants showed an increase relative to their baseline levels, while in the
      presence of growth factors pretreatment, hair cells showed a relative reduction
      in calcium levels. Pretreatment of organ of Corti explants afforded significant
      protection of hair cell stereocilia bundle morphology from ototoxic damage when
      compared to explants exposed to ototoxin alone. This study correlates a rise in
      hair cell calcium levels with the otoprotection of hair cells by TGF alpha in
      organ of Corti explants.

PMID- 9263034
TI  - Viral-mediated gene transfer in the cochlea.
AB  - Gene transfer is an exciting new tool in medical therapy and scientific
      investigation, but only very recently has it begun to be developed in the
      auditory system. This paper describes in vivo and ex vivo experiments using an
      adenoviral vector (Ad. RSVntlacZ), which is a replication-deficient virus based
      on a human adenoviral (serotype 5) genomic backbone. The in vivo experiments
      demonstrate successful gene transfer into multiple types of cochlear cells. We
      observed a relatively efficient transduction, several weeks of sustained
      transgene expression and an absence of major lethal cytotoxicity in spiral
      ganglion and epithelial cells of the cochlea in adult animals. The ex vivo
      experiments were performed using fibroblasts transduced in vitro with Ad.
      RSVntlacZ. Two weeks after inoculation of the fibroblasts into the perilymph, we
      observed transplanted fibroblasts, which were adherent to the lining of the
      perilymphatic spaces, and were expressing the lacZ transgene. We speculate that,
      as the genetic basis of degenerative cochlear diseases is characterized on a
      mutational level, transgene expression will allow us to test hypotheses regarding
      the effects of specific genes on cochlear cell biology. Gene transfer will not
      only increase our understanding of the pathophysiology of hearing loss, but also
      may provide gene therapy for disease.

PMID- 9263033
TI  - Mice with a targeted disruption of the neurotrophin receptor trkB lose their
      gustatory ganglion cells early but do develop taste buds.
AB  - The alleged ability of taste afferents to induce taste buds in developing animals
      is investigated using a mouse model with a targeted deletion of the tyrosine
      kinase receptor trkB for the neurotrophin BDNF. This neurotrophin was recently
      shown to be expressed in developing taste buds and the receptor trkB has been
      shown to be expressed in the developing ganglion cells that innervate the taste
      buds. Our data show a reduction of geniculate ganglion cells to about 5% of
      control animals in neonates. Degeneration of ganglion cells starts when processes
      reach the central target (solitary tract) but before they reach the peripheral
      target (taste buds). Degeneration of ganglion cells is almost completed in trkB
      knockout mice before taste afferents reach in control animals the developing
      fungiform papillae. Four days later the first taste buds can be identified in
      fungiform papillae of both control and trkB knockout mice in about equal number
      and density. Many taste buds undergo a normal maturation compared to control
      animals. However, the more lateral and caudal fungiform papillae grow less in
      size and become less conspicuous in older trkB knockout mice. No intragemmal
      innervation can be found in trkB knockout taste buds but a few extragemmal fibers
      enter the apex and end between taste had cells without forming specialized
      synapses. Taste buds of trkB knockout mice appear less well organized than those
      of control mice, but some cells show similar vesicle accumulations as control
      taste bud cells in their base but no synaptic contact to an afferent. These data
      strongly suggest that the initial-development of many fungiform papillae and
      taste buds is independent of the specific taste innervation. It remains to be
      shown why others appear to be more dependent on proper innervation.

PMID- 9263035
TI  - Novel genes expressed in the chick otocyst during development: identification
      using differential display of RNA.
AB  - Differential display of mRNA is a technique that enables the researcher to
      compare genes expressed in two or more different tissues or in the same tissue or
      cell under different conditions. The method is based on polymerase chain reaction
      amplification and comparison of specific subsets of mRNA. We have used this
      method to clone partial complementary DNAs (cDNAs; amplicons) for genes expressed
      in the otocyst in order to identify genes that may be involved in development of
      the inner ear. A full length cDNA was isolated from an embryonic quail head
      library with an amplicon (KH121) obtained from the otocyst. This avian cDNA
      encoded a novel, 172-amino acid acidic protein and detected a major transcript of
      ca 0.8 kb in RNA from chick embryos and several neonatal chick tissues. The full
      length avian cDNA had high sequence identity to several human cDNAs (expressed
      sequence tags) from human fetal tissues, including cochlea, brain, liver/spleen
      and lung, and from placenta. The human homologue of the avian gene encoded a
      protein that was 183 amino acids long and had 75.6% amino acid sequence identity
      to the avian protein. These results identified both the avian and human
      homologues of an evolutionarily conserved gene encoding a small acidic protein of
      unknown function; however, expression of this gene was not restricted to
      otocysts.

PMID- 9263037
TI  - Time course of nerve-fiber regeneration in the noise-damaged mammalian cochlea.
AB  - The time course of events which are essential for nerve-fiber regeneration in the
      mammalian cochlea was determined using a group of chinchillas that had been
      exposed for 3.5 hr to an octave band of noise with a center frequency of 4 kHz
      and a sound pressure level of 108 dB. The animals recovered from 40 min (0 days)
      to 100 days at which times their inner ears were fixed and the organs of Corti
      prepared for phase-contrast and bright-field microscopy as plastic-embedded flat
      preparations. Selected areas identified in the flat preparations were semi-thick
      and thin sectioned at radial or tangential angles for examination by bright-field
      and transmission electron microscopy. The following time-ordered events appeared
      critical for nerve-fiber regeneration: (1) The area of the basilar membrane in
      which regeneration had a possibility of occurring showed signs of severe injury.
      Outer hair cells degenerated first followed by outer pillars, inner pillars,
      inner hair cells and other supporting cells; (2) Myelinated nerve fibers in the
      osseous spiral lamina became fragmented, starting at the distal ends of the
      fibers. This degeneration gradually extended back to Rosenthal's canal; (3)
      Fibrous processes, originating from Schwann-like cells in the osseous spiral
      lamina, extended laterally on the basilar membrane; (4) Schwann cells lined up
      medial to the habenulae perforata in the areas of severest damage, apparently
      ready to migrate through the habenulae onto the basilar membrane; (5) Schwann
      cell nuclei appeared on the basilar membrane beneath the developing layer of
      squamous epithelium which was in the process of replacing the degenerated portion
      of the organ of Corti; (6) Regenerated nerve fibers with thin myelin sheaths or a
      simple investment of Schwann cell cytoplasm appeared in areas of total loss of
      the organ of Corti; and (7) The myelin sheaths on the regenerated nerve fibers
      gradually became thicker.

PMID- 9263036
TI  - Transfection of neonatal rat cochlear cells in vitro with an adenovirus vector.
AB  - A recombinant adenovirus vector containing a beta-galactosidase reporter gene was
      used to transfect neonatal rat organ of Corti or spiral ganglion explants in
      vitro. Infection at appropriate titers (10(6)-10(7) pfu/ml) transduced virtually
      all cells in the cultures after 72 hr. However, spiral ganglion neurons and cells
      in the inner hair cell regions of the organ of Corti showed the highest levels of
      expression. Viral titers that produced high levels of beta-galactosidase
      expression did not appear to damage the cultures, and did not inhibit neurite
      outgrowth from spiral ganglion cells. However, higher titers (10(8)-10(9) pfu/ml)
      clearly diminished explant viability and inhibited neurite extension. The results
      demonstrate that cochlear cells can be transfected successfully with an
      adenovirus vector, at viral titers which do not induce obvious signs of cellular
      damage or dysfunction.

PMID- 9263038
TI  - Implication of NMDA type glutamate receptors in neural regeneration and
      neoformation of synapses after excitotoxic injury in the guinea pig cochlea.
AB  - In the adult mammalian cochlea, the ability of nerve fibres to regenerate has
      been observed following disruption of the organ of Corti by various means, or
      transsection of the cochlear nerve in the internal auditory meatus. Based upon
      the implication of glutamate as a neurotransmitter at synapses between sensory
      hair cells and terminal dendrites of the auditory nerve in the mammalian cochlea,
      we have developed, in a previous study, an in vivo model of neural regeneration
      and formation of synapses after the destruction of the afferent nerve endings by
      local application of the glutamate agonist alpha-amino-3-hydroxy-5-methyl
      isoxazol-propionic acid (AMPA). In situ hybridization experiments performed
      during the re-innervation process revealed an overexpression of mRNA coding for
      NR1 subunit of N-methyl-D-aspartate (NMDA) receptors in the spiral ganglion
      neurons, suggesting that these receptors are implicated in neural regenerative
      processes. The present study has been designed to study the functional
      implication of NMDA receptors in the regrowth and synaptic repair of auditory
      dendrites in the guinea pig cochlea, by blocking the NMDA receptors during the
      period of normal functional recovery. In a first set of experiments, we recorded
      compound action potential after acute perilymphatic perfusion of cumulative doses
      (0.03-10mM) of DL 2-amino-5-phosphonovalerate (D-AP5), a NMDA antagonist, to
      determine the efficiency of the drug. In a second set of experiments, the
      auditory dendrites were destroyed by local application of the glutamate agonist
      AMPA. The blockage of NMDA by the antagonist D-AP5 applied with an osmotic
      micropump delayed the functional recovery and the regrowth of auditory dendrites.
      The findings of our study support the hypothesis that, in addition to acting as a
      fast transmitter, glutamate has a neurotrophic role via the activation of NMDA
      receptors.

PMID- 9263040
TI  - Pre- and postnatal expression of glycoconjugates (3-fucosyl-N-acetyllactosamine
      and HNK-1 epitopes) in the mouse inner ear.
AB  - The distribution of two glycoconjugates 3-fucosyl-N-acetyllactosamine (CD15) and
      HNK-1 epitope (CD57) in the inner ear of the NMRI mouse was analysed from the
      eighth day of gestation to the 16th day after birth. CD15 epitope distribution is
      developmentally regulated. The up- and down-regulation of expression, the change
      in the number of cells which are positive, the ingrowth of CD15-positive cells
      and their distribution, intracellular and/or cell-surface-associated expression,
      all assume a characteristic appearance at each developmental stage. Distribution
      of CD57 documented the nerve outgrowth and formation of the innervation of the
      vestibular apparatus and cochlear duct. Correlation between CD15 and CD57
      expression patterns revealed differences in the interaction of the ingrowing
      fibres and epithelial tissue between the vestibular organ and the cochlea and
      differences in the development of the cristae and maculae.

PMID- 9263039
TI  - Neurotrophins can enhance spiral ganglion cell survival after inner hair cell
      loss.
AB  - Following destruction of sensory cells of the organ of Corti, spiral ganglion
      cells (SGC) in the guinea pig degenerate. Chronic electrical stimulation via
      cochlear prostheses can enhance their survival, with the effect blocked by
      stopping the electrically elicited action potentials with tetrodotoxin. Blocking
      action potentials in the normal hearing ear with tetrodotoxin, however, does not
      cause degeneration. This suggests that in the pathological ear VIII N activity
      acts as a survival factor, while in the normal ear there are other survival
      factors that maintain SGCs. We examined neurotrophins, as survival factors in the
      deafened ear. Two weeks of treatment with BDNF (brain derived neurotrophic
      factor) administered chronically via a mini-osmotic pump into scala tympani at 50
      ng/ml, provided a statistically significant enhanced SGC survival over untreated
      deafened ears or deafened ears treated with artificial perilymph. Neurotrophin 3
      provided some enhanced survival, but this was not statistically significant over
      untreated deafened ears. These observations suggest there are survival factors in
      the inner ear, including those coupled to direct activation of the auditory nerve
      fibers, that may serve to maintain the auditory nerve. These factors may be
      applied following deafness to maintain and enhance neural populations and to
      increase benefits to the profoundly deaf receiving cochlear implants.

PMID- 9263041
TI  - Polysialic acid in the cochlea of the developing mouse.
AB  - Polysialic acid (PSA), an unusual molecule covalently attached to the neural cell
      adhesion molecule, NCAM, has been shown to regulate cell-to-cell and cell-to
      matrix interactions by interfering with the binding of cell-surface adhesion
      molecules. We used immunocytochemistry to map the temporospatial distribution of
      PSA in the mouse cochlea between embryonic day 16 and postnatal day 32 and
      compared it to the known timetable of neural growth and development. Polysialic
      acid immunoreactivity develops along a temporospatial gradient beginning in the
      basal turn and progressing to the apical turn. The expression is transitory on
      spiral ganglion neurons, intraganglionic bundles, radial bundles, and outer hair
      cells. Immunoreactivity diminishes progressively from the basal turn to the
      apical turn. Immunolabeling is maintained to adulthood on fibers in the inner
      spiral and inner pillar bundles, bundles which have been suggested to sprout
      continually and grow even in older animals. Inner hair cells are never
      immunolabeled. The temporo-spatial expression of PSA suggests its involvement in
      neural growth, whereas its extinction correlates with the time of onset of nerve
      receptor interactions.

PMID- 9263043
TI  - Henry Perly Rusk, 1884-1954: a brief biography.

PMID- 9263042
TI  - The development of vestibulocochlear efferents and cochlear afferents in mice.
AB  - We have reinvestigated the embryonic development of the vestibulocochlear system
      in mice using anterograde and retrograde tracing techniques. Our studies reveal
      that rhombomeres 4 and 5 include five motor neuron populations. One of these, the
      abducens nucleus, will not be dealt with here. Rhombomere 4 gives rise to three
      of the remaining populations: the facial branchial motor neurons; the vestibular
      efferents; and the cochlear efferents. The migration of the facial branchial
      motor neurons away from the otic efferents is completed by 13.5 days post coitum
      (dpc). Subsequently the otic efferents separate into the vestibular and cochlear
      efferents, and complete their migration by 14.5 dpc. In addition to their common
      origin, all three populations have perikarya that migrate via translocation
      through secondary processes, form a continuous column upon completion of their
      migrations, and form axonal tracts that run in the internal facial genu. Some
      otic efferent axons travel with the facial branchial motor nerve from the
      internal facial genu and exit the brain with that nerve. These data suggest that
      facial branchial motor neurons and otic efferents are derived from a common
      precursor population and use similar cues for pathway recognition within the
      brain. In contrast, rhombomere 5 gives rise to the fourth population to be
      considered here, the superior salivatory nucleus, a visceral motor neuron group.
      Other differences between this group and those derived from rhombomere 4 include
      perikaryal migration as a result of translocation first through primary processes
      and only then through secondary processes, a final location lateral to the
      branchial motor/otic efferent column, and axonal tracts that are completely
      segregated from those of the facial branchial and otic efferents throughout their
      course inside the brain. Analysis of the peripheral distribution of the cochlear
      efferents and afferents show that efferents reach the spiral ganglion at 12.5 dpc
      when postmitotic ganglion cells are migrating away from the cochlear anlage. The
      efferents begin to form the intraganglionic spiral bundle by 14.5 dpc and the
      inner spiral bundle by 16.5 dpc in the basal turn. They have extensive
      collaterals among supporting cells of the greater epithelial ridge from 16.5 dpc
      onwards. Afferents and efferents in the basal turn of the cochlea extend through
      all three rows of outer hair cells by 18.5 dpc. Selective labeling of afferent
      fibers at 20.5 dpc (postnatal day 1) shows that although some afferents are still
      in early developmental stages, some type II spiral ganglion cells already extend
      for long distances along the outer hair cells, and some type I spiral ganglion
      cells end on a single inner hair cell. These data support previous evidence that
      in mice the early outgrowth of afferent and efferent fibers is essentially
      achieved by birth.

PMID- 9263044
TI  - Influence of postpartum weight and body condition change on duration of anestrus
      by undernourished suckled beef heifers.
AB  - Two experiments were conducted to determine the relationship between change in
      weight and body condition on postpartum interval of thin first-calf beef heifers.
      Twenty-nine (Exp. I) and 36 (Exp. II) Angus and Angus-sired crossbred heifers
      were limit-fed to reduce their condition score (BCS) to 4 (scale of 1 to 9) at
      calving. After calving, heifers were assigned to one of four daily ME intakes
      (range of 198 to 305 kcal ME/kg BW.75) designed to create a range of BCS changes.
      Each unit change in BCS was associated (R2 = .72; P < .0001) with a 33-kg weight
      change. Mean postpartum interval (PPI) from calving to initiation of luteal
      activity was 121 +/- 6.0 d. As dietary energy density increased, PPI decreased (P
      < .01). Condition score at calving (CCS) accounted for a greater proportion of
      the variation (R2 = .37) associated with PPI than did condition score change from
      calving to d 90 postpartum (CSCH90; R2 = .27) or weight change from calving to d
      90 postpartum (WTCH90; R2 = .17). The "best fit" equation (R2 = .56) for
      predicting PPI included CCS and CSCH90: PPI = 244.5 - 28.28(CCS) - 23.07(CSCH90)
      + 6.36(CSCH90(2)). Maximum reduction in PPI occurred when heifers gained 1.8
      units of BCS during the first 90 d of lactation. Gaining BCS at a faster rate was
      of no additional benefit.

PMID- 9263046
TI  - The effect of adding further traits in index selection.
AB  - The effect on genetic and economic response of adding further traits in index
      selection was studied. This was done first using the true parameters and then
      using simulated parameter estimates and with "bending" to ensure consistent
      matrixes. The extra responses obtained in the full aggregate genotype were
      expressed as a percentage of the response before adding the trait. For simplicity
      the cases studied were limited to 2 to 4 traits, and to a range of simple
      parameter sets. The extra response from adding a further trait in index selection
      was very variable, but was often very large. As a simple rule, adding a trait
      with a high relative product (ah2) of the standardized economic weight (a) and
      heritability (h2) gave large extra response. Adding a trait with lower ah2 value
      gave less extra response. The extra responses were smaller if the correlations
      between the added trait and other traits with high relative ah2 were favorable
      and were larger if the correlations were unfavorable. With estimated parameters,
      the results from adding a further trait in index selection were more variable.
      For many cases the increase in the response was still large but for some cases
      the response was reduced. With poor parameter estimates the number of traits in
      index selection should be limited to those with the larger values of ah2. As the
      parameter estimates improve, more traits can be added without reducing overall
      genetic response. Even though some general tendencies have been discerned, there
      was much variation in the extra responses obtained.

PMID- 9263045
TI  - Estrus and luteal function in suckled beef cows that were anestrous when treated
      with an intravaginal device containing progesterone with or without a subsequent
      injection of estradiol benzoate.
AB  - The objectives in this study were to determine whether treatment with
      progesterone (P4) via an intravaginal device would induce estrus and development
      of corpora lutea (CL) with typical life spans and whether treatment with
      estradiol benzoate (EB) following device removal would enhance the responses. At
      treatment initiation (d 0), suckled beef cows (n = 362) that were anestrous
      received one of the following: 1) an intravaginal device containing P4 for 7 d
      plus an injection of 1 mg of EB 24 to 30 h after device removal (P4+EB), 2) an
      intravaginal device containing P4 for 7 d (P4), 3) a sham device for 7 d plus an
      injection of 1 mg of EB 24 to 30 h after device removal (EB), or 4) a sham device
      for 7 d (control). Progesterone treatment increased the proportion of cows that
      formed CL with a typical lifespan (P < .001) and exhibited behavioral estrus (P <
      .05). Treatment with EB in combination with P4 increased (P < .001) the
      proportion of cows that exhibited estrus. Treatment with P4 alone had no effect,
      but the combination of P4 and EB increased (P < .01) the proportion of cows that
      formed short-lived or typical lifespan CL by the end of the experiment compared
      with untreated cows. In summary, treatment with P4 increased the incidence of
      estrus and the proportion of cows that formed CL with a typical lifespan.
      Treatment with P4 resulted in resumption of luteal function in suckled beef cows
      that were anestrous, with most cows developing CL with a typical lifespan,
      whereas EB enhanced the expression of estrus.

PMID- 9263047
TI  - Optimum postweaning test for measurement of growth rate, feed intake, and feed
      efficiency in British breed cattle.
AB  - The optimum duration of test for measurement of growth rate, feed intake, feed
      conversion, and residual feed intake was examined using postweaning feed intake
      and weight data from 760 Angus, Hereford, Polled Hereford, and Shorthorn heifer
      and Angus bull progeny from 78 sires. Variance components, heritability,
      phenotypic and genetic correlations, and the efficiency of selection using
      shortened tests compared with a 199-d test were used as criteria to assess the
      optimum test length. The results indicated that a 35-d test was sufficient for
      measurement of feed intake, whereas a 70-d test was required to measure growth
      rate, feed conversion, and residual feed intake without compromising the accuracy
      of measurement. When a 70-d test is used to measure growth rate, feed conversion,
      and residual feed intake there is minimal loss in accuracy when weights are
      collected every 2 wk instead of weekly, but a further increase in the interval
      between weights to 5 wk caused a decline in the accuracy of the test. Therefore a
      70-d test with cattle weighed every 2 wk seems to be optimal for measuring these
      traits in British breed cattle.

PMID- 9263049
TI  - Approximate confidence intervals for heritability from method R estimates.
AB  - Method R estimates of heritability (h2) and associated confidence intervals (CI)
      were obtained from simulated data using a single trait, direct effects, full
      animal model, with 50% subsampling. Five hundred data sets were simulated for
      each of five levels of h2 (.10, .20, .30, .40, and .50) and two types of pedigree
      structure (random pedigree structure [N = 2,000] that varied over simulations, or
      the pedigree structure from a real data set [N = 2,644] that was constant for all
      simulations). The first 10, 20, and all 50 h2 estimates were used to obtain 80,
      90, 95, and 99% CI for each data set. The variance of h2 estimates within data
      sets approximated the sampling variance of the h2 estimates. The Box-Cox
      transformation was used to normalize the distribution of estimates from each data
      set. Confidence intervals were computed on the transformed scale as CI = mu +/-
      (T x sigma), where mu and sigma = the mean and SD of the N transformed h2
      estimates, respectively, and T = the critical value from the T distribution for a
      1-alpha CI, with df = N-1. Upper and lower CI bounds were converted back to the
      original scale by reversing the transformation. The percentages of CI containing
      the true h2 value, pooled across all levels of h2, types of pedigree, and number
      of estimates used to obtain CI, for 80, 90, 95, and 99% CI were 81.14, 90.96,
      95.27, and 98.76%, respectively. These results suggested that Method R h2
      estimates can be used to obtain reliable CI.

PMID- 9263048
TI  - Response to selection for fertility in a fall-lambing sheep flock.
AB  - Selection for fertility in a fall lambing system was applied for 5 yr (1.45
      generations) in a crossbred sheep population. Three flocks were involved: a fall
      lambing selected (S) flock of 125 ewes and 10 rams, a fall-lambing environmental
      control (EC) flock of 55 ewes and five rams, and a spring-lambing genetic control
      flock of 45 ewes and five rams used to produce replacements for EC. Estimated
      breeding values for fertility (ewes lambing per ewe exposed) were calculated for
      animals mated in each year of the study using a single-trait animal model and
      increased more rapidly in S (.0138/yr) than in EC (.0067/yr). After accounting
      for genetic drift, EBV of ewes mated in S in the final year of the study averaged
      .070 +/- .032 (P = .08). A correlated response of .0087 lambs/yr was observed in
      S for fall litter size Genetic trends in all body weights were positive in EC,
      likely because of supplemental selection on body size in ram lambs used in EC.
      Ninety-day weight, maternal effects on weaning weight, and 90-d scrotal
      circumference increased in S, but direct effects on birth and weaning weights
      declined. In order to focus on realized selection response in fertility, EBV for
      fertility of 330 replacement ewe lambs from S and EC were calculated using only
      data collected after their birth. These realized EBV were then regressed on
      pedigree EBV calculated at the time the ewe lambs were born. The regression was
      significant when all relationships were used to calculate both EBV (.20 +/- .08)
      but only approached significance (.13 +/- .07) when only records of the ewe lambs
      themselves, their descendants, and their paternal half-sibs were used to
      calculate realized EBV. Also, EBV for all ewes were calculated at the start of
      each breeding season and were higher (P < .01) for ewes that subsequently lambed
      than for open ewes. These results suggest that selection can be used to improve
      fertility in fall-lambing sheep flocks.

PMID- 9263050
TI  - Mapping genomic regions associated with growth rate in pigs.
AB  - The objective of this study was to identify genomic regions associated with
      postweaning average daily gain (ADG) in swine. Two families were produced using
      sires obtained from the cross of lines divergently selected for high and low
      growth rate. Sires were mated to 29 unrelated dams that produced 124 and 115
      offspring. Average daily gain was recorded for every individual; mean ADG was
      .593 +/- .007 kg/d and .619 +/- .009 kg/d in the two families. Selective
      genotyping was performed as a prescreening procedure to identify genomic regions
      potentially associated with ADG. A total of 75 genetic markers were used between
      both families. Markers identified as nominally significant (P < .05) in an
      individual marker analysis were subsequently typed in all individuals. Markers
      still nominally significant (P < .05) after analysis with the complete family
      were then reevaluated together with flanking markers in an interval mapping
      analysis. A single region on chromosome 3, flanked by markers Sw2429 and Sw251,
      for the second family had a logarithm of the odds score of 2.9, which is
      suggestive of linkage with a quantitative trait locus for ADG. Differences were
      .033 +/- .009 kg/d between individuals inheriting alternative paternal alleles
      for Sw251, which was the most significant marker.

PMID- 9263051
TI  - Nutrient flows in agriculture in The Netherlands with special emphasis on pig
      production.
AB  - Annual nitrogen (N), phosphorus (P), and potassium (K) flows in agriculture in
      The Netherlands were identified and quantified in 1990, with special emphasis on
      pig production. Also, the effects that various management strategies in pig
      production have on NPK emission in 1990 were compared using a static
      deterministic simulation model. Ammonia emission from pig production in 1990
      (60.9 Gg N) exceeded the defined target for the year 2000 (12.7 Gg N). Measures
      that affect volatilization of ammonia directly (i.e., introduction of low
      emission stables, manure storage facilities, or manure application techniques)
      reduced ammonia emission most effectively. These measures, however, should be
      combined with a reduction in application of artificial N fertilizer to avoid an
      increase in N losses through leaching, run-off, or denitrification. Targets for
      ammonia emission in the year 2010 require a reduction in the pig population of 24
      to 62%, in addition to implications of measures described in this article.
      National NPK losses in 1990 through leaching, run-off, or denitrification,
      predicted at 223.5 kg/ha for N, 32.7 kg/ha for P, and 67 kg/ha for K, exceeded
      government targets for the year 2010 (185 kg N/ha; 8.7 kg P/ha; norm not set for
      K). Reducing application of artificial NPK fertilizer reduced national NPK losses
      most effectively. For P, use of phytase and feeding pigs in accordance with their
      P requirements is required, in addition to limited use of artificial P fertilizer
      to meet targets for the year 2010. Hence, from an environmental point of view,
      pig production in The Netherlands is limited primarily by ammonia emission
      targets for the year 2010.

PMID- 9263052
TI  - Behavior of cattle during hot-iron and freeze branding and the effects on
      subsequent handling ease.
AB  - Three hundred feedlot steers (320 +/- 2 kg) were assigned to freeze brand, hot
      iron brand, and sham branding treatments according to a randomized branding
      arrangement. Behaviors believed to be indicative of pain (i.e., tail-flicking,
      kicking, falling, and vocalizing) were recorded during branding. Escape behavior,
      measured as the amount and duration of force exerted on the headgate and squeeze
      chute by the animals during treatment, was obtained using load cells and strain
      gauges. Subsequent handling ease following branding was tested every 2nd d for 10
      d by recording the time and effort required to move animals into the chute. Hot
      iron-branded steers had greater tail-flick, kick, fall and vocalization
      frequencies than freeze-branded or sham-branded animals (P < .005). However,
      freeze-branded animals differed from shams only in regard to tail-flick
      frequencies (P < .005). The average and maximum exertion forces and the duration
      of force were greater in hot-iron-than in freeze- and sham-branded steers (P <
      .001); freeze branded steers had greater values than shams (P < .001). No
      treatment differences in handling ease were observed. However, all steers
      required more handling effort for up to 6 d, indicating that handling, per se,
      was aversive. Results indicate that hot-iron-branded steers experienced more
      discomfort at the time of branding than freeze-branded and sham steers, and
      freeze-branded steers experienced more discomfort than shams.

PMID- 9263053
TI  - Preference of sheep and goats for extracts from high-grain concentrate.
AB  - Appetite stimulants were extracted and partially isolated from high-grain
      concentrate. The stimulants were fed daily and were palatable to sheep and goats
      used in the experiments. The stimulative effects were tested by comparing the
      intake of two types of hay: with or without the extracts. Diethylether and n
      pentane extracts of the concentrate stimulated feeding in sheep (P < .01 and P <
      .05, respectively). However, methanol extracts had no significant stimulative
      effect on selective feeding in sheep. Goats also preferentially fed on hay
      sprayed with the diethyl ether extracts (P < .01). The diethyl ether extracts
      were divided into acid, neutral, and basic fractions. Sheep and goats had a
      marked preference for the acid fraction only (P < .01 and P < .05, respectively).
      These results suggest that specific chemicals to increase palatability of hay are
      present in high-grain concentrate and that the chemical are nonpolar, acidic
      substances.

PMID- 9263054
TI  - Preference among cooling systems by gilts under heat stress.
AB  - A preference experiment was conducted to compare and evaluate the use of three
      cooling systems by mature gilts. Systems evaluated were snout coolers (S), drip
      coolers (D), and conductive cool pads (P). Preference for cooling system and pen
      position were continuously monitored and evaluated during daily heat stress
      conditions (34.2 +/- 2.8 degrees C), nightly warm conditions (26.6 +/- 2.3
      degrees C), and for total time. The physiological variables of respiration rate
      (RR) and rectal temperature (Tr) were measured at three separate times daily.
      Gilts naive to the cooling systems were individually housed in pens with three
      free stalls, each stall containing a different cooling system. After 1 d of warm
      temperature (27.6 +/- 2.5 degrees C) acclimation, gilts were exposed to 10 h of
      the heat stress conditions and 14 h of the warm night conditions each day for six
      consecutive days. Cooling system use was higher during the hot period (80.2%)
      than during the warm period (66.2%). The conductive cool pad was preferred over
      the drip cooler (P < .02) and the snout cooler (P < .0002). The preference for
      the conductive cool pad persisted in the warm period. Cooling system use had a
      significant effect on Tr and RR (P < .001). The Tr (P < .005) and RR were lower
      (P < .005) with the use of the conductive cool pad, whereas the drip cooler and
      snout cooler showed no effect on these variables.

PMID- 9263055
TI  - Insulin sensitivity and responsiveness of portal-drained viscera, liver,
      hindquarters, and whole body of beef steers weighing 275 or 490 kilograms.
AB  - Our objective was to quantify effects of age, weight, and body composition on
      responsiveness (Rmax or Rmin) and sensitivity (ED50) of several parameters of
      glucose metabolism to insulin in growing beef steers. Steers ate equal-sized
      meals every 2 h; the diet contained 62% concentrate and sustained 1 kg ADG.
      Treatments were euglycemic clamps at 10, 20, 40, 80, 160, and 320 mU.h-1.kg BW-1
      of insulin infused into a mesenteric vein of seven younger (275 kg BW) and seven
      older (490 kg BW) steers. Most steers received three of the six treatments; two
      extra steers were added to compensate for missing data. Steers had blood vessel
      catheters and ultrasound flow probes that allowed measurement of net uptake or
      release of glucose and insulin by portal-drained viscera (PDV), liver, and
      hindquarters (HQ). Steady-state glucose infusion rate (SSGIR) was intrajugular
      glucose infused during treatments to maintain euglycemia. Within age groups, Rmax
      or Rmin and ED50 were estimated by nonlinear regression of glucose flux on
      arterial plasma insulin concentrations. Steers were killed after sampling,
      tissues were weighted, and HQ content of fat and protein was determined. Those
      data were used to predict tissue weights and HQ composition at the time of the
      euglycemic clamps. Predicted EBW (243 vs 444 kg), liver (4.24 vs 6.19 kg), and HQ
      (73 vs 122 kg) were heavier for older than for younger steers. Fat in HQ was
      higher for older than for younger steers (173 vs 134 g/kg), but protein was
      similar (198 g/kg). The ED50 (mU of insulin/L of plasma) for SSGIR (237 +/- 65 vs
      113 +/- 22), liver glucose release (89 +/- 22 vs 44 +/- 11), total glucose entry
      (418 +/- 184 vs 125 +/- 20), and HQ glucose uptake (488 +/- 151 vs 243 +/- 78)
      was higher for older than for younger steers. The Rmax (mmol glucose.h-1.kg
      tissue-1) for SSGIR (2.68 +/- .22 vs 2.09 +/- .23) and HQ (3.08 +/- .33 vs 2.46
      +/- .30) was higher for younger than for older steers. Liver glucose release
      decreased in response to insulin; Rmin (mmol glucose.h-1.kg liver-1) was higher
      for younger (36.0 +/- 6.9) than for older (24.7 +/- 3.2) steers. We conclude that
      as steers grew older, heavier, and fatter, their peripheral tissues and liver
      became less sensitive and less responsive to insulin.

PMID- 9263056
TI  - The response of transgenic mice to beta-adrenergic agonist administration is
      different from that of normal mice.
AB  - Eighteen transgenic mice carrying an ovine metallothionein la-ovine growth
      hormone (oMTla-oGH) transgene and 18 littermate normal mice were used to
      investigate the effects of transgene expression and clenbuterol administration on
      growth performance and skeletal muscle characteristics. The oGH transgene was
      activated from 21 d of age, and half of the mice were fed 15 ppm clenbuterol from
      42 to 70 d of age. All mice were killed at 70 d of age after 4 wk of treatment,
      and organs and muscles were dissected, weighted, and analyzed. Transgenic mice
      (TM) gained 2.6 times more than normal mice (NM). However, TM had a significantly
      lower (-20%, P < .01) proportion of muscle, expressed as percentages of body
      weights, and a higher percentage of heart (+10%), liver (+26%, P < .01) and
      spleen (+64%, P < .01) than NM. Clenbuterol improved the weight gain of TM by
      20%, compared with 10% for NM. The growth-promoting effect of clenbuterol was
      almost exclusively confined to skeletal muscle (24% increase) in NM, in contrast
      to a more generalized growth increase in all tissues including skeletal muscle
      (11% increase) in TM. The skeletal muscles of TM were longer but smaller in
      diameter due to 30% smaller muscle fiber cross-sectional area. Clenbuterol
      increased the muscle fiber size of all fiber types by 60% in NM, compared to 30%
      in TM. Muscle DNA concentrations and content were higher (P < .05) in TM than in
      NM, and clenbuterol administration decreased DNA concentrations but not total DNA
      content for both genotypes. Cathepsin B, C, and H activities were higher (P <
      .01) in TM muscle, but the significance is not clear at the present time,
      although it points to a potential for greater protein degradation and(or)
      turnover rates as suggested by smaller muscle weights.

PMID- 9263057
TI  - Effect of the callipyge phenotype and cooking method on tenderness of several
      major lamb muscles.
AB  - We conducted three experiments to determine the effects of the callipyge
      phenotype on the tenderness of several major lamb muscles and to determine the
      effect of method of cookery on the tenderness of callipyge lamb at 7 d
      postmortem. In Exp. 1, chops from normal (n = 23) and callipyge (n = 16)
      carcasses were open-hearth-broiled. Warner-Bratzler shear force values of
      longissimus, gluteus medius, semimembranosus, biceps femoris, semitendinosus,
      adductor, and quadriceps femoris were 123, 44, 28, 26, 19, 16, and 13% greater,
      respectively, for callipyge (P < .05). In Exp. 2, muscles from normal (n = 18)
      and callipyge (n = 18) carcasses were oven-roasted. Shear force of triceps
      brachii was 11% greater for callipyge (P < .001); however, phenotype did not
      affect shear force of supraspinatus (P = .87) or psoas major (P = .64). In Exp.
      3, a trained sensory panel evaluated leg roasts and open-hearth-broiled leg chops
      from normal (n = 60) and callipyge lamb carcasses (n = 60). Callipyge chops were
      less tender than normal chops (P < .05). Regardless of callipyge phenotype,
      muscles were more (P < .05) tender when roasted; however, the effect of method of
      cookery on tenderness scores was greater for callipyge muscles than for normal
      muscles. Callipyge roasts and normal roasts had similar tenderness (P = .58), and
      callipyge roasts were more tender than normal chops (P < .05). Regardless of
      cooking method, callipyge samples were less juicy than normal samples (P < .05).
      These data demonstrate that the callipyge phenotype will likely reduce consumer
      satisfaction due to reduced tenderness and juiciness; however, reduced tenderness
      in callipyge leg muscles could be prevented by ovenroasting.

PMID- 9263058
TI  - Effect of rapid rigor mortis processes on protein functionality in pectoralis
      major muscle of domestic turkeys.
AB  - The pale, soft, exudative (PSE) phenomenon in turkey pectoralis major (breast)
      muscle was studied using a combination of biochemical, meat quality, microscopic,
      and gel electrophoresis techniques. Breast muscle samples were collected from
      turkeys characterized by slow vs fast postmortem glycolysis assessed by muscle pH
      at 20 min after death. The PSE group was characterized by lower muscle ATP (P <
      .05) and higher lactate levels (P < .05) compared with the normal group. Excess
      water-holding capacity and cooking yield were significantly lower (P < .05) in
      the PSE group than in normal turkeys. Breast muscle of the PSE group was also
      lighter (P < .05) than that in the normal group as determined by Minolta L*
      values. The SDS-PAGE, Western blotting, and immunofluorescence microscopy
      revealed that phosphorylase, a soluble enzyme, became tightly associated with the
      myofibrils in muscle from the PSE group. Also, less myosin could be solubilized
      from PSE vs normal myofibril samples. The results indicate that irreversible
      myosin insolubility due to low pH and high-temperature conditions is decisive in
      the development of PSE turkey breast muscle.

PMID- 9263059
TI  - Increasing valine, isoleucine, and total branched-chain amino acids for lactating
      sows.
AB  - One hundred eighty-five (n = 24 to 27/group; average parity 1.3) sows (PIC, Line
      C-15) were used to evaluate effects of the interrelationship between isoleucine
      and valine on sow and litter performance. Diets were formulated to .90% total
      lysine with all amino acids other than isoleucine and valine at least 110% of
      their suggested requirement estimate relative to lysine using ratios derived from
      the National and Agricultural Research Councils. The control diet was formulated
      to .50% isoleucine and .72% valine. L-Valine and L-isoleucine replaced cornstarch
      to provide .72 or 1.07% dietary valine, and .50, .85, or 1.20% isoleucine. A
      seventh diet contained .50% isoleucine and 1.42% valine. Mean litter size after
      cross-fostering was 11.1 pigs, and average lactation length was 20.3 d. No valine
      x isoleucine interactions were observed (P > .10) for most response criteria.
      Number of pigs weaned (mean = 10.9), sow feed intake (mean = 6.13 kg), and lysine
      intake (mean = 55 g/d) were not affected by dietary isoleucine or valine. Litter
      weight and weight gain at weaning increased as dietary valine (P < .07),
      isoleucine (linear, P < .07), and total branched-chain amino acids (linear, P <
      .02) increased. Twelve sows per treatment (84 total) were milked manually on
      either d 17 or 18 of lactation. Increasing dietary valine increased milk DM and
      fat (linear, P < .01). Milk DM, CP, and fat increased (linear, P < .002) as
      dietary isoleucine increased. The casein fraction of milk protein increased
      (linear, P < .01) and whey and nonprotein N fractions decreased (linear, P < .06,
      P < .01, respectively) as dietary isoleucine increased. Based on these results,
      valine and isoleucine increased litter weights. The independent increases in
      litter weaning weights from adding valine and isoleucine suggest separate modes
      of action in lactating sows.

PMID- 9263060
TI  - The efficacy of Aspergillus niger phytase in rendering phytate phosphorus
      available for absorption in pigs is influenced by pig physiological status.
AB  - We performed an experiment with 112 piglets, 32 growing-finishing pigs, and 12
      sows during pregnancy and lactation to test the hypotheses that apparent total
      tract digestibilities of P and Ca as well as the efficacy of Aspergillus niger
      phytase in rendering phytate P available in pigs depend on pig physiological
      status. All pigs were fed diets with identical feedstuff composition either
      without or with added microbial phytase (Natuphos, 500 FTU/kg diet). The diets
      contained 6.2 g Ca, 4.8 g total P, and 3.7 g phytate P per kilogram, and
      intrinsic phytase activity of 120 FTU/kg. The digestibility of P increased by 8.3
      percentage units when BW of pigs increased from 30 to 60 kg and then remained
      stable until 100 kg. Pregnant sows had a lower efficiency of P absorption than
      piglets and growing-finishing pigs. During lactation, the efficiency of P
      absorption was 3.4 percentage units higher than during pregnancy but was still
      6.6 percentage units lower than for growing-finishing pigs. The efficacy of the
      phytase in generating digestible P decreased in the order or lactating sows,
      growing-finishing pigs, sows at the end of pregnancy, piglets, and sows at
      midpregnancy; the average amounts of generated digestible P were 1.03, .83, .74,
      .66, and .32 g/kg diet, respectively. The addition of phytase to the diet raised
      apparent Ca digestibility in the piglets and growing-finishing pigs (by 4.6 and
      4.0 percentage units, respectively) but not in the sows. We conclude that in the
      formulation of swine diets the amount of phytase to be added should be tailored
      to the target category.

PMID- 9263061
TI  - Factors affecting phosphorus and calcium digestibility in diets for growing
      finishing pigs.
AB  - In two experiments, we investigated various factors that affect the estimation of
      the apparent total tract digestibility (ATTD) of DM, Ca, and total P in diets for
      growing-finishing pigs. In Exp. 1, the effects of age, housing, and calculation
      method (indicator [Cr2O3] vs 10-d total collection) were determined. Eighteen
      barrows and gilts (40 to 95 kg BW) were housed in six pens, and ATTD was
      estimated using the indicator method. Twelve barrows were housed in metabolic
      crates, and ATTD was estimated using both calculation methods. Dietary treatments
      were 1) a tapioca-soybean-barley-based diet, 2) Diet 1 supplemented with 400 FTU
      microbial phytase/kg of diet, and 3) a corn-soybean meal-based diet: In Exp. 2,
      six barrows (95 to 120 kg BW) were fed a phytase-deficient diet to investigate
      the effects of coprophagy (40 g fresh feces/kg of diet) and movement. Pigs were
      fed at 2.8 times maintenance requirement (418 kJ ME/BW.75); water supply was 2.5
      L/kg of feed. The ATTD increased as BW increased. Phytase enhanced total P ATTD
      by an average of 18.1 percentage units. The ATTD of DM was higher and the ATTD of
      Ca and total P (P < .001) were lower in pigs housed in pens than in pigs housed
      in metabolic crates. Fecal consumption and movement led to numerical increases in
      Ca (P = .217) and total P (P = .103) ATTD. Estimates of Ca and total P ATTD using
      pigs in metabolic crates are lower than estimates in practice.

PMID- 9263062
TI  - The effects of sow parity on digestibility of proximate components and minerals
      during lactation as influenced by diet and microbial phytase supplementation.
AB  - Ninety-six (Finnish Landrace x Dutch Landrace) reproductive sows were used at
      parities 1, 3, 5, and 7 + 8 from d 107 of gestation to d 21 of lactation to
      investigate the effects of diet and parity on apparent total tract digestibility
      (ATTD). Animals were randomly assigned to one of four dietary treatments. Dietary
      treatments were 1) a P-deficient (1.1 g digestible P [dP]/kg) Dutch semipractical
      diet; 2) Diet 1 supplemented with 400 FTU Aspergillus niger phytase per kilogram
      of diet (1.7 g dP/kg); 3) a corn-soybean meal-based diet (1.3 g dP/kg); and 4)
      Diet 3 supplemented with extra monocalcium phosphate (MCP; 2.4 g dP/kg of diet).
      Animals were fed twice daily at 2.8 times maintenance (418 kJ ME/ BW75) from d 8
      to the end of lactation. Feces and urine were collected during d 11 to 13 and d
      18 to 20 of lactation. The ATTD of DM, OM, ash, CP, Ca, Mg, and total P (P < .01)
      were higher for the corn-soybean meal-based diets than for the Dutch
      semipractical diet not supplemented with phytase. Addition of MCP enhanced total
      P ATTD by an average of 6.7 percentage units. Addition of microbial phytase
      improved Ca, Mg, and total P ATTD, but the effects were dependent on the stage of
      lactation. Lower ATTD of OM and CP were seen for first parity animals compared
      with higher parity sows. The ATTD of Mg increased with increasing parity. Parity
      had little effect on the ATTD of minerals during lactation, and dietary effects
      were prominent and followed a similar trend to those seen in growing-finishing
      pigs.

PMID- 9263063
TI  - Use of a raw meat-based diet or a dry kibble diet for sand cats (Felis
      margarita).
AB  - Limited information is available on the utilization of different types of diets
      by captive exotic felid species. Utilization of diets by small exotic felids may
      differ depending on the diet fed. Eight sand cats (Felis margarita), which are
      small, 2- to 4-kg cats, were used to examine the digestibility of two types of
      diets: a raw meat-based diet and a dry kibble diet. Dry matter, crude protein and
      energy intakes and digestibilities were evaluated. Digestibilities for dry
      matter, energy, and crude protein were 83.5 +/- 4.8, 89.6 +/- 5.2, 92.4 +/- 5.3%
      for the raw meat-based diet and 72.7 +/- 12.3, 76.8 +/- 14.5, and 77.9 +/- 13.5%
      for the kibble diet. Physiological variables also were examined and included
      plasma taurine, vitamin A, retinyl palmitate, beta-carotene, calcium, and
      phosphorus. Plasma taurine means were 91.4 +/- 8.4 mumol/L in cats consuming the
      raw meat-based diet and 248.0 +/- 23.2 mumol/L in cats consuming the kibble diet.
      Plasma phosphorus was 5.2 +/- .1 and 4.5 +/- .1 mg/dL, respectively, in cats
      consuming raw meat-based and kibble diets. beta-Carotene was 25.2 +/- 2.9 and 2.9
      +/- .3 micrograms/dL, respectively, for cats consuming the raw meat-based and
      kibble diets. These results indicate that diets formulated for small captive
      exotic felid species should be evaluated with respect to diet type and nutrient
      utilization.

PMID- 9263064
TI  - Technical note: pig model for studying nutrient assimilation by the intestine and
      colon.
AB  - We have developed a system for chronically catheterizing 10- to 25-d-old pigs
      that permits stable isotope tracer studies of intestinal or colonic assimilation
      of nutrients. This model also can be used to ensure constant enteral feeding or
      to assess the rate of entry into the terminal ileum of carbohydrates, fats, and
      amino acids. A plastic cannula with a luminal flange can be surgically placed in
      the stomach for tracer studies of sugar digestion or for controlled infusion of
      any formula diet. A similar cannula can be placed in the cecum for infusion of
      tracer and(or) substrates for studies of fermentation. The cannula has been
      machined so that a washer and nut can be threaded onto it, allowing the entire
      apparatus to be fixed to the abdominal wall. The distal end protruding above the
      skin was tapered to fit standard i.v. extension tubing. A carotid arterial
      catheter was used to sample substrates for isotopic enrichment measurements.

PMID- 9263065
TI  - Growth and physiological responses to toxicosis in lines of mice selected for
      resistance or susceptibility to endophyte-infected tall fescue in the diet.
AB  - In three experiments, mice from lines selected for resistance (R) or
      susceptibility (S) to growth depression from endophyte-infected fescue seed in
      the diet were fed diets containing infected (E+) or non-infected (E-) seed.
      Activities of liver enzymes known to participate in oxidation, reduction, or
      hydrolysis or in conjugation of xenobiotics were measured in these mice. In all
      experiments, E+ caused greater reduction in initial ADG of S than of R mice. In
      Exp. 1, liver cytochromes P450 and b5 activities were not affected by line, diet,
      or their interaction. These enzymes were not evaluated in subsequent experiments.
      In all experiments, glutathione-S-transferase (GST) and uridine diphosphate
      glucuronosyltransferase (GRT) activities differed between lines. Resistant mice
      had significantly higher GST activity on both diets in Exp. 1, on E- in Exp. 2,
      and on E+ in Exp. 3. Resistant mice had higher GRT activities on E+ in Exp. 1, on
      E- in Exp. 2, but after 4 wk on either diet in Exp. 3. Before test diets were
      imposed in Exp. 3, GST and GRT activities were higher in R-line mice. Divergent
      selection created lines that differed in response to tall fescue in the diet.
      Postweaning growth of resistant mice was less severely depressed by E+, although
      susceptible mice later expressed compensatory gain. Activities of two
      detoxification enzymes generally were higher in livers from R-line mice,
      suggesting a biochemical mechanism for the difference. Using such traits, it may
      be possible to select ruminants for resistance to fescue toxicosis.

PMID- 9263066
TI  - Estimating the maximum effective dose in a quantitative dose-response experiment.
AB  - A simulation study was conducted to compare several procedures for estimating the
      maximum effective dose in a quantitative dose-response experiment. Using four
      equally spaced dose levels, data were generated from four different model types:
      the quadratic growth curve, the Mitcherlich growth curve, the linear-linear
      plateau spline model, and the quadratic-linear plateau spline model. Each model
      type was parameterized to create three different model ranges, and for each
      range, data were generated from populations with three different standard
      deviations. The existence of unique dose-response curves is assumed; thus, all
      the procedures compared in this paper require that the data have been modeled by
      a polynomial or nonlinear regression model. An attempt was made to fit each
      generated data set with each of the four model types. Maximum effective dose
      estimation procedures were applied to a data set only when the data were
      adequately described by a given model. The stimulation indicated that the
      estimate of the maximum effective dose is influenced more by the choice of model
      than by the method of estimation. Because of the consistently low estimates
      produced when the data were modeled by the linear-linear plateau spline, this
      model is not recommended for use an maximum effective dose estimation
      experiments. The simulation also demonstrated that the design failed to provide
      sufficient information about the form of the dose-response curve. Designs with
      more than four dose levels should be considered.

PMID- 9263068
TI  - Conception failure in swine: importance of the sex ratio of a female's birth
      litter and tests of other factors.
AB  - Failure of gilts and sows to conceive when they are mated is a potentially
      serious economic cost for swine producers. In Exp. 1, we determined that
      anogenital distance of newborn gilts is related to the proportion of males in the
      litter (P < .001). Gilts from litters with more males have larger anogenital
      distances (mean = 8.0 +/- .2 mm); those from litters with low proportions of
      males have smaller anogenital distances (mean = 5.7 +/- .1 mm). In Exp. 2, we
      examined the effect of birth litter sex ratio of sows and gilts on reproductive
      performance using a 13-yr database of breeding and litter data. Gilts that failed
      to become pregnant on the first breeding attempt came from litters with
      significantly higher proportions of males than gilts that successfully conceived
      on the first breeding attempt. Overall, female swine were significantly more
      likely to exhibit lower rates of successful breeding during their first four
      breeding attempts if they had been born in a male-biased litter. These results
      have implications for swine producers deciding which gilts to keep and which to
      market. Given the higher probability of reproductive problems for gilts from
      litters of 12 or more pigs with 67% or more males, these females should likely
      become market hogs. Sow's age, mode of insemination, and the number of
      insemination attempts at an estrus period, but not season, can affect successful
      breeding.

PMID- 9263067
TI  - Effect of feeding blends of Fusarium mycotoxin-contaminated grains containing
      deoxynivalenol and fusaric acid on growth and feed consumption of immature swine.
AB  - Experiments were conducted to determine the effect of feeding diets containing
      combinations of the Fusarium metabolites deoxynivalenol (DON) and fusaric acid
      (FA) to starter swine. In all experiments, pigs of approximately 8.2 kg initial
      weight were fed diets containing blends of mycotoxin-contaminated corn, wheat,
      and barley for 21 d with growth and feed consumption determined weekly. In the
      first experiment, diets were determined to contain 0 microgram DON/g + 58.9
      micrograms FA/g (control), 4.4 micrograms DON/g + 57.1 micrograms FA/g, 6.0
      micrograms DON/g + 48.6 micrograms FA/g, and 7.5 micrograms DON/g + 57.4
      micrograms FA/g. The feeding of all diets containing DON caused significant
      linear depressions in growth and feed intake after only 1 wk. Lower
      concentrations of DON and FA were fed in the second experiment with diets
      containing 0 microgram DON/g + 16.3 micrograms FA/g (control), .5 microgram DON/g
      + 14.3 micrograms FA/g, 1.1 micrograms DON/g + 14.1 micrograms FA/g, and 1.9
      micrograms DON/g + 13.6 micrograms FA/g. There was a significant linear reduction
      in feed intake after 1 wk with increasing levels of dietary DON. Weight gains
      declined significantly only after 3 wk. Increasing amounts of FA combined with
      relatively constant amounts of DON were fed in the third experiment. By analysis,
      diets contained .5 micrograms DON/g + 2.9 micrograms FA/g (control), 2.2
      micrograms DON/g + 12.2 micrograms FA/g, 2.5 micrograms DON/g + 15.6 micrograms
      FA/g, and 2.4 micrograms DON/g + 15.9 micrograms FA/g. In the 1st wk, the feeding
      of increasing amounts of fusaric acid combined with a relatively constant amount
      of DON caused a significant linear depression in weight gain. We concluded that a
      toxicological synergism exists between DON and FA when fed to immature swine and
      that FA concentrations in feeds should be determined whenever DON analysis is
      conducted.

PMID- 9263069
TI  - Relationships of light and heavy fetuses to uterine position, placental weight,
      gestational age, and fetal cholesterol concentrations.
AB  - With emphasis on increasing litter size to improve productivity and
      profitability, lightweight pigs born will increase in number as litter size
      increases and may be problematic due to reduced neonatal survival of lightweight
      pigs. To study developmental aspects of lightweight fetuses, fetal and placental
      weights were evaluated at three stages of pregnancy (30, 70, and 104 d) from
      white composite gilts (n = 88, 123, and 135, respectively) in relation to uterine
      position of light and heavy fetuses. Fetal cholesterol concentrations were
      analyzed at the beginning (d 70) and end (d 104) of the in utero growth phase
      (last third of gestation). At 30 d of gestation, no differences were noted
      between fetal weight and position within the uterine horn, but at 70 d and 104 d
      of pregnancy, heavy fetuses were found at the tubal ends and light fetuses at the
      cervical ends of the uterus. Using the criteria of +/- 1 SD or +/- 2 SD of the
      mean and lower and upper 10 or 20% of fetal weights for each gestational age,
      light and heavy fetuses in conjunction with their placentas were different from
      population means at all stages of gestation. Cholesterol concentrations were
      lower in light fetuses (d 104) and increased in heavy fetuses. In 28 litters (d
      104) selected for extremes in within-litter fetal weights, concentrations of IGF
      I increased with fetal weight (P < .01), which suggests that growth and
      development of lightweight pigs may be limited by critical endocrine components.

PMID- 9263070
TI  - Transfer of an ovine metallothionein-ovine growth hormone fusion gene into swine.
AB  - An ovine metallothionein-1a (oMT1a)-ovine growth hormone (oGH) fusion gene was
      microinjected into 400 pig zygotes, the zygotes were transferred into recipient
      females, and 15 founder transgenic pigs were born. Of 12 transgenic pigs assayed,
      five expressed high levels of oGH (> 900 ng/mL plasma), one expressed low levels
      of oGH (10 to 30 ng/mL), and six did not express oGH. Dietary supplementation
      with 2,000 ppm of zinc for 6 d induced a 20-fold increase in plasma oGH in the
      transgenic pig with low expression but did not induce expression in the six
      transgenic pigs with no constitutive oGH expression. The average daily gain of
      five transgenic pigs with elevated oGH was similar to that of non-transgenic
      littermates during a 9-wk feeding trial (P = .52). The liver, kidney, adrenal,
      and thyroid weights were all significantly heavier for the oGH-expressing
      transgenic pigs than for non-transgenic littermates. Total carcass fat,
      longissimus muscle fat, subcutaneous backfat thickness, and loin eye area were
      lower and carcass protein and water content and beta R fiber area of longissimus
      muscle were higher in the transgenic pigs with elevated oGH than in their
      littermate controls (P < .05 for each). The data indicate that even though the
      oMT1a promoter was more inducible by zinc than was previously reported for the
      mouse MT promoter in swine, the former provided a higher level of oGH expression
      than the mouse MT promoter.

PMID- 9263072
TI  - Current perspective on assessing site of digestion in ruminants.
AB  - The site of nutrient digestion in the gastrointestinal tract of ruminants affects
      nutrient availability and the nature of digestive end-products supplied to the
      host animal. Methods to study site of digestion in vivo provide a tool to obtain
      data that enhance the ability to interpret or predict animal responses to some
      feeding practices. Examples are discussed for which site of digestion data
      provided insights that might not have been evident from other approaches. The use
      of site of digestion techniques may provide interpretation regarding digestion of
      N by ruminants different from those derived from measurement of total tract N
      digestion. Site of digestion measurements have been particularly important in
      studying effects of heat processing of protein sources and in understanding the
      nature of digestion of N in high-quality, fresh forages. Moreover, site of
      digestion techniques have been instrumental in interpreting the influences of
      supplemental fat sources on ruminal digestion and ruminal biohydrogenation and
      small intestinal digestion of long-chain fatty acids.

PMID- 9263071
TI  - In vitro determination of ruminal protein degradability of alfalfa and prairie
      hay via a commercial protease in the presence or absence of cellulase or
      driselase.
AB  - Ruminal protein degradation of alfalfa (2.62% N, 49.6% NDF, and in vivo
      undegradable intake protein [UIP] = 16.4% of CP) and prairie hay (.88% N, 69.4%
      NDF, and in vivo UIP = 44.5% of CP) was estimated using the Streptomyces griseus
      protease (SGP) in vitro method with or without pretreatment with two
      carbohydrases: cellulase from Penicillium funiculosum or driselase from
      Basidiomycetes. Driselase is a broad-spectrum carbohydrase. Incubating forage
      samples for 48 h with cellulase or driselase at a concentration of 800 mg/g per g
      of hay nearly maximized ADF and NDF disappearances. This concentration and
      incubation time then were used to pretreat hay samples. A 2-h pretreatment was
      included to evaluate the potential for reducing the analysis time. Other sets of
      samples were or were not pretreated with acetate buffer alone. Following
      pretreatment, samples were subjected to SGP for .25, .5, 1, 2, 4, 8, 12, 24, and
      48 h. Pretreatment altered the sizes of protein pools and their degradation
      rates. When the UIP contents of the forages were estimated using SGP and a single
      pool, first-order, kinetic model, cellulase (48 h) or driselase pretreatments
      yielded UIP predictions that were more similar to in vivo values. Some
      carbohydrase and protease combinations also yielded single time-point estimates
      of UIP that were similar to in vivo values. Similarly, when sufficient time was
      permitted for protease incubation, single time-point estimates derived from
      protease alone were similar to in vivo values.

PMID- 9263073
TI  - Design and interpretation of nutrient digestion studies.
AB  - A variety of factors influence the results of digestion studies designed to
      measure ruminal disappearance of nutrients and flow of nutrients to the
      intestine. Feed intake, marker usage, sample collection, statistical design, and
      computation methods are among the factors discussed in this review. Guidelines
      are provided for presentation and interpretation of data from digesta flow
      studies. The scientific value of such studies often is limited because 1)
      replication, relative to expected variation, is inadequate and 2) experimental
      animals are not maintained under conditions similar to those used in normal
      production. Because studies conducted with inappropriate methods or inadequate
      replication are of little value and waste resources, validation of techniques is
      critical, and individual researchers should strive to verify their techniques.

PMID- 9263074
TI  - Considerations for gastrointestinal cannulations in ruminants.
AB  - The complexity of ruminant digestion necessitates a greater variety and
      complexity of experimental methods than with any other species. The fact that
      dietary ingredients are first subjected to microbial fermentation requires
      elaborate measures to ascertain nutrients presented for absorption. Numerous
      approaches have been attempted to obtain representative samples of digesta at
      sites throughout the gastrointestinal tract. The choices of a researcher before
      an experiment include animal(s), site(s) for cannula placement, style of cannula,
      cannula material, and numerous other more subtle factors that may contribute to
      the success of an experiment. This review compares the advantages and
      disadvantages of various approaches, cannula types, and cannula materials that
      should be considered before experiments are conducted.

PMID- 9263075
TI  - Alternative techniques for measuring nutrient digestion in ruminants.
AB  - Because in vivo measurement of nutrient digestion in the rumen and small
      intestine requires ruminally and intestinally cannulated animals that are
      expensive, labor-intensive, and subject to error associated with markers and
      inherent animal variation, alternative techniques have been developed.
      Researchers have proposed various in situ or in vitro procedures for estimating
      ruminal and small intestinal nutrient digestion. This review summarizes these
      alternative techniques.

PMID- 9263076
TI  - Ruminal fermentation and nutrient digestion in sheep fed hydroxyethylsoyamide.
AB  - Hydroxyethylsoyamide (HESA) was reported previously to protect soybean oil from
      ruminal biohydrogenation and increase plasma unsaturated fatty acids in sheep.
      Two digestibility trials with sheep and a rumen in vitro trials were conducted in
      this study to determine the effects of HESA on ruminal VFA and nutrient
      digestibility. Trial 1 was a 4 x 4 Latin square with 17-d periods in which four
      wethers were fed either a control diet (CON) with no added fat, 2.5% soybean oil
      (SBO), 5% butylsoyamide (BuSA), or 5% HESA. The HESA diet was ground with a
      mortar and pestle before feeding to disperse fat lumps that formed during diet
      mixing. Compared with the CON diet, the HESA diet reduced DMI, acetate/
      propionate (A/P), and total tract fiber digestibility, but these were not
      affected by SBO or BuSA. Trial 2 was a 24-h rumen in vitro study showing that
      total VFA concentration and A/P in cultures were reduced by 10% linoleic acid but
      not by 10% ethanolamine or 10% HESA. In Trial 3, four wethers were fed the CON
      and HESA diets in a replicated 2 x 2 Latin square to determine digestibility
      responses to HESA when grinding was avoided. Fiber digestibilities and A/P were
      not affected by HESA in Trial 3. The HESA in this study had variable effects on
      fiber digestibility that may have been related to physical attributes of the
      diet, including particle size. Substitution of ethanolamine for butylamine during
      synthesis of the amide increased fatty acid digestibility but reduced dry matter
      intake.

PMID- 9263077
TI  - Rapid communication: nucleotide sequence of ovine mitochondrial genes for tRNA
      glycine and cytochrome c-oxidase subunit III.

PMID- 9263078
TI  - Rapid communication: restriction fragment length polymorphism in amplification
      products of the porcine growth hormone-releasing hormone gene.

PMID- 9263079
TI  - Rapid communication: mapping the pig VCAM1 locus to chromosome 4 using a double
      stranded conformation polymorphism marker (VCAM1-2).

PMID- 9263080
TI  - Rapid communication: a restriction fragment length polymorphism in the porcine
      leptin receptor (LEPR) gene.

PMID- 9263081
TI  - Computerized recordkeeping and information management in cardiothoracic and
      vascular anesthesia.

PMID- 9263082
TI  - Computerized data collection in the operating room during coronary artery bypass
      surgery: a comparison to the hand-written anesthesia record.
AB  - OBJECTIVE: To investigate variability between hand-written and computerized
      anesthesia records and evaluate any associated bias. DESIGN AND MEASUREMENTS: A
      computer system that was used to collect intraoperative data for a study of
      hemodynamic management during coronary artery bypass graft surgery is described.
      The system collected and recorded hemodynamic data automatically downloaded from
      the anesthesia monitor as well as surgical events and drug administration data
      entered through menu options. The system then combined, summarized, and graphed
      the data as well as formatted it for export to a commercially available database
      program. In a sample of 14 patients, blood pressure data collected by the
      computer system was compared with the blood pressure data charted in the hand
      written anesthesia record. MAIN RESULTS: Although general linear models
      controlling for within-patient variation and randomization assignment for mean
      arterial pressure range on cardiopulmonary bypass showed a significant
      relationship; low R2 values indicated that much of the variability could not be
      explained and that there was, therefore, poor agreement between the two records.
      Furthermore, a systematic bias in the hand-written anesthesia record was found
      when the computer system record was compared with the hand-written record and to
      the difference of the two records, so that extremes seen in the computer system
      record tended to be minimized in the hand-written anesthesia record. CONCLUSIONS:
      Because of the lack of explained variability between the computer system and hand
      written anesthesia records and the bias in the hand-written anesthesia record,
      the hand-written anesthesia record should not be relied on as a source of
      accurate data for research purposes.

PMID- 9263083
TI  - Anesthesia and minimally invasive thoracoscopically assisted coronary artery
      bypass: a brief clinical report.
AB  - OBJECTIVE: To examine the anesthesia implications of minimally invasive
      thoracoscopically assisted coronary artery bypass (MITACAB) surgery. DESIGN: A
      combined retrospective and prospective observational report of patients
      undergoing MITACAB surgery. SETTING: A community heart center. PARTICIPANTS:
      Patients having MITACAB surgery. INTERVENTIONS: None specifically related to the
      report. MAIN RESULTS: The MITACAB approach was found to be successful in
      completing left internal mammary artery (LIMA) to left anterior descending
      coronary artery (LAD) bypass in 17 of 20 patients. No patient required emergency
      institution of cardiopulmonary bypass or defibrillation during the procedure.
      However, 6 of the 17 patients who underwent the MITACAB surgery required
      transvenous pacing at the time of surgery. None of 17 patients who underwent
      MITACAB surgery has required additional cardiovascular intervention since the
      time of surgery. Stroke volume and pulmonary arterial pressures were generally
      unaffected during performance of the bypass graft. CONCLUSION: MITACAB requires
      special anesthetic interventions; however, MITACAB appears to be a safe,
      effective approach to LIMA-to-LAD bypass.

PMID- 9263084
TI  - The effects of cardiopulmonary bypass on total and unbound plasma concentrations
      of propofol and midazolam.
AB  - OBJECTIVE: To examine the effects of cardiopulmonary bypass (CPB) on total and
      unbound plasma concentrations of propofol and midazolam when administered by
      continuous infusion during cardiac surgery. DESIGN: Prospective clinical study.
      SETTING: University hospital. PARTICIPANTS: Twenty-four adult patients undergoing
      cardiac surgery. INTERVENTIONS: Patients received either propofol or midazolam to
      supplement fentanyl anesthesia. Twelve patients received a propofol bolus (1
      mg/kg) followed by an infusion of 3 mg/kg/hr. A second group received midazolam,
      0.2 mg/kg bolus, followed by an infusion of 0.07 mg/kg/hr. MEASUREMENTS AND MAIN
      RESULTS: Blood sample were collected from the radial artery cannula at 0, 2, 4,
      8, 8, 10, 15, 20 minutes and then every 10 minutes before CPB, at 1, 2, 3, 4, 6,
      10, 15, 20 minutes and then each 10 minutes during CPB. On weaning from CPB
      samples were collected at 0, 5, 10 and 20 minutes. Plasma binding, total and
      unbound propofol and midazolam concentrations were determined by ultrafiltration
      and high-pressure liquid chromatography (HPLC). CPB resulted in a fall in total
      propofol and midazolam plasma concentrations, but the unbound concentrations
      remained stable. The propofol unbound fraction increased from 0.22 +/- 0.06% to
      0.41 +/- 0.17%. The midazolam unbound fraction increased from 5.6 +/- 1.0% to
      11.2 +/- 2.1%. CONCLUSIONS: Unbound concentrations of propofol and midazolam are
      not affected by cardiopulmonary bypass. Total intravenous anesthesia algorithms
      do not need to be changed to achieve stable unbound plasma concentrations when
      initiating CPB.

PMID- 9263085
TI  - Bolus administration of eltanolone, thiopental, or etomidate does not affect
      systemic vascular resistance during cardiopulmonary bypass.
AB  - OBJECTIVE: To discover possible effects on systemic vascular resistance of the
      anesthetic induction agent eltanolone in comparison with thiopental and
      etomidate. The measurements were performed during cardiopulmonary bypass to
      maintain a constant cardiac output (approximately pump flow). DESIGN: The
      patients were prospectively randomized in three groups to receive either
      eltanolone, thiopental, or etomidate. SETTING: University hospital as a single
      center. PARTICIPANTS: Seventy-five patients scheduled for elective coronary
      artery bypass grafting. INTERVENTIONS: The anesthetic induction agents were
      repeated at the same dosage when cardiopulmonary bypass was instituted. The
      respective mean dosages were eltanolone, 0.41 +/- 0.1 mg/kg; thiopental, 2.88 +/-
      0.62 mg/kg; etomidate, 0.26 +/- 0.06 mg/kg. MEASUREMENTS AND MAIN RESULTS:
      Systemic vascular resistance was calculated from the mean of a triple measurement
      (normal pump flow and +/- 20%). Points of measurement were before, and 2 and 5
      minutes after injection of the hypnotic agent. None of the injected drugs made a
      significant change in the systemic vascular resistance. A small (not significant)
      decrease from 1,295 +/- 296 dyne/s/cm-5 to 1,196 +/- 323 dyne/s/cm-5 (mean +/-
      SD) was seen in the eltanolone group, whereas the other patients did not show any
      change during the study period. CONCLUSIONS: The reason for the significant
      reduction of the arterial pressure attributed to anesthetic induction by
      eltanolone may be more a cardiodepressive effect than a direct vasodilation.

PMID- 9263086
TI  - Concentration of cefamandole in plasma and tissues of patients undergoing cardiac
      surgery: the influence of different cefamandole dosage.
AB  - OBJECTIVE: To develop an improved regimen of antibiotic prophylaxis in cardiac
      surgery, three antibiotic prophylactic regimens for patients scheduled to have
      elective cardiothoracic surgery involving a median sternotomy were evaluated.
      DESIGN: A prospective, randomized, unblinded study. SETTING: A university
      teaching hospital. PARTICIPANTS: Sixty-nine men scheduled for elective coronary
      artery bypass grafting (CABG) with extracorporeal circulation (ECC) were included
      in the study. INTERVENTIONS: The patients were selected at random to receive 2 g
      of cefamandole (CM) at induction of anesthesia (group 1, n = 24), or 2 g of CM at
      the beginning of anesthesia followed by an additional dose (2 g) immediately
      after onset of cardiopulmonary bypass (CPB) (group 2, n = 22), or 4 g of CM just
      at the initiation of anesthesia (group 3, n = 23). Samples from the mammary
      artery, sternum, and plasma were obtained at various intervals after injection of
      the antibiotic (10 minutes intravenously) to compare antibiotic levels, assayed
      for CM concentrations, with high-pressure liquid chromatography (HPLC) and plasma
      bactericidal activity as well as infectious complications in these sites as a
      function of time for the three groups. MEASUREMENTS AND MAIN RESULTS: There were
      no significant differences in biometric data, duration of hospitalization, or
      management of cardiopulmonary bypass, including urinary tract drainage and
      infusion volume. The mean plasma t1/2 (distributive or alpha-phase) before bypass
      was 51.7 +/- 16.7 minutes for group 1 and 2 patients and 54.9 +/- 15.9 minutes
      for group 3 patients. CM plasma values were significantly higher in group 2
      (170.3 +/- 105.8 micrograms/mL) than in groups 1 and 3 (111.8 +/- 42.2
      micrograms/mL, 101.2 +/- 57.2 micrograms/mL) at the end of bypass periods (p <
      0.05). The antibiotic contents of mammary artery and sternum samples of group 2
      (15.6 +/- 4.7 micrograms/mL, 9.5 +/- 4.7 micrograms/mL) were significantly higher
      after completion of CPB compared with group 1 (5.7 +/- 1.9 micrograms/mL, 3.8 +/-
      2.9 micrograms/mL) and group 3 (6.3 +/- 3.5 micrograms/mL, 3.6 +/- 1.8
      micrograms/mL) (p < 0.05). There were no significant differences in distribution
      of micro-organisms among the three groups, but two patients of groups 1 and 3
      with plasma and tissue CM levels below minimal inhibitor concentration (MIC90)
      for Hemophilus influencea, E coli, Proteus ssp and Klebsiella ssp after
      completion of CPB, respectively, developed a pneumonia postoperatively caused by
      Hemophilus influencea (1), E coli (1) and Klebsiella ssp (2) (p < 0.05).
      CONCLUSIONS: It would be preferable to infuse the antibiotic shortly before the
      operative procedure. However, to keep tissue and plasma CM values more than MIC90
      for common pathogens during the time period studied, a second infusion of 2 g of
      CM administered after onset of CPB suggests better protection against the risk of
      microbial infections. Therefore, the findings might be important for the choice
      of antibiotic prophylaxis, particularly for high-risk patients.

PMID- 9263087
TI  - Endogenous nitric oxide and low systemic vascular resistance after
      cardiopulmonary bypass.
AB  - OBJECTIVES: To investigate the relationship between excessive endogenous
      production of nitric oxide (NO) and the low systemic vascular resistance (SVR)
      syndrome after cardiac surgery. DESIGN: Prospective, case-control. Cases defined
      by low SVR postoperatively (< 750 dyn/s/cm-5), and matched with controls (> 900
      dyn/s/cm-5). SETTING: Cardiothoracic intensive care unit (ICU) in a tertiary care
      hospital. PARTICIPANTS: Forty-four patients after cardiac surgery. INTERVENTIONS:
      Collection of plasma and urine samples after identification. MEASUREMENTS AND
      MAIN RESULTS: Plasma and urine nitrate concentrations were measured as an index
      of endogenous NO production. Hemodynamic, inotropic, and outcome data were
      collected. Median nitrate concentrations did not differ between cases and
      controls (plasma, 58 mumol/L, v 62 mumol/L, p = 0.43; urine, 399 mumol/L v 404
      mumol/L, p = 0.38). Times to extubation and intensive care unit (ICU) discharge
      were prolonged in patients with low SVR (17.8 hours v 8.7 hours, p = 0.021; 2.5
      days v 1.2 days, p = 0.019, respectively). CONCLUSIONS: No association between
      "low SVR syndrome" and endogenous NO production was found. Patients with low SVR
      after cardiac surgery required a longer period of inotropic and ventilator
      support, with delay in discharge from the ICU. The risk and cost implications of
      this syndrome support further research.

PMID- 9263088
TI  - Neutrophil expression of CD11b/CD18 and IL-8 secretion during normothermic
      cardiopulmonary bypass.
AB  - OBJECTIVE: To assess blood polymorphonuclear neutrophil (PMN) activation status
      during normothermic cardiopulmonary bypass (CPB), the expression of the PMN
      adhesion molecule CD11b/CD18 was measured. Basal state as well as ex vivo
      capacity of PMN to be stimulated by a bacterial peptide (FMLP) were investigated.
      Because interleukin-8 (IL-8) is known to induce CD11b/CD18 expression in vitro in
      PMN, IL-8 plasma levels were concomitantly measured. DESIGN: Prospective study.
      SETTING: University hospital. PARTICIPANTS: Thirteen patients scheduled for
      cardiac surgery. INTERVENTIONS: Systemic arterial and pulmonary arterial blood
      samples were withdrawn at the same moment during the first 4 hours after the
      onset of CPB. MEASUREMENTS AND MAIN RESULTS: Twenty minutes after the onset of
      CPB, basal expression of PMN CD11b/CD18 was upregulated, whereas IL-8 plasma
      levels remained unchanged. The increase in PMN CD11b expression was maintained
      until the fourth hour after the onset of CPB. At this time, elevation of IL-8
      plasma levels was maximal. No differences were found between pulmonary and
      systemic arterial IL-8 plasma levels, even after aortic unclamping. The capacity
      of PMN to be stimulated ex vivo by FMLP remained normal. CONCLUSIONS:
      Normothermic CPB induced a fast increase in CD11b expression, which appeared to
      be similar to that observed during hypothermia. IL-8 was probably not related to
      the very early CD11b upregulation, but could be involved in pulmonary PMN
      sequestration during pulmonary reperfusion and contribute to the maintained
      expression of PMN CD11b. Although partially activated, PMNs maintain a normal
      capacity to respond to a further FMLP stimulation and thus to bacterial
      infection.

PMID- 9263089
TI  - A human urinary protease inhibitor (ulinastatin) inhibits neutrophil
      extracellular release of elastase during cardiopulmonary bypass.
AB  - OBJECTIVES: To determine the benefits of a human urinary protease inhibitor
      (ulinastatin) on postoperative pulmonary dysfunction associated with neutrophil
      activation during cardiopulmonary bypass. DESIGN: A prospective, randomized,
      clinical study. SETTING: The study was performed at Keio University Hospital,
      Tokyo. PARTICIPANTS: Eighteen adult patients scheduled for primary cardiac
      surgery. INTERVENTIONS: The patients were randomly assigned either to the control
      group (n = 8) or to the group (n = 10) receiving ulinastatin (600,000 U in
      total). MEASUREMENTS AND MAIN RESULTS: Human neutrophil ability to release
      elastase in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) in
      vitro was measured before and after cardiopulmonary bypass, together with plasma
      levels of neutrophil elastase complex, interleukin-B, and C3a. Intrapulmonary
      shunt fraction was then calculated. Neutrophil elastase release in response to
      fMLP significantly increased in the control group, but remained unchanged in the
      ulinastatin group. In addition, ulinastatin minimized the increase of plasma
      neutrophil elastase, independently of the production of interleukin-B or C3a.
      Simultaneously, ulinastatin ameliorated the increase of intrapulmonary shunt,
      which was correlated with extracellular elastase release. CONCLUSIONS:
      Ulinastatin attenuated the elevation of fMLP-induced elastase release, which was
      associated with the deterioration of gas exchange during cardiopulmonary bypass.
      The administration of this agent has a potential to lessen the risk of
      postperfusion lung injury.

PMID- 9263090
TI  - Enalaprilat decreases plasma endothelin and atrial natriuretic peptide levels and
      preload in patients with left ventricular dysfunction after cardiac surgery.
AB  - OBJECTIVE: To study the acute effects of angiotensin-converting enzyme inhibition
      by intravenous enalaprilat infusion in patients with left ventricular dysfunction
      after cardiac surgery. DESIGN: Prospective, consecutive sample, before-after
      trial. SETTING: Surgical intensive care unit in a tertiary care university
      hospital. PARTICIPANTS: Eight patients with left ventricular dysfunction after
      cardiac surgery. Patients were defined as having left ventricular dysfunction if
      the pulmonary capillary wedge pressure persisted above 18 mmHg in spite of
      conventional vasoactive medication (inotropic or vasodilating and diuretic drugs)
      and intermittent mandatory ventilation during the first postoperative week.
      INTERVENTIONS: Enalaprilat was infused initially at 1 mg/ hour. The rate was
      doubled every 30 minutes until pulmonary capillary wedge pressure decreased at
      least 20% or until a maximum total dose of 10 mg was achieved. MEASUREMENTS AND
      RESULTS: Central hemodynamics, systemic oxygenation, and hormonal regulation of
      circulation (plasma renin activity, plasma endothelin, atrial natriuretic
      peptide, norepinephrine, epinephrine, and vasopressin concentrations, serum
      angiotensin-converting enzyme activity, and serum levels of aldosterone) were
      assessed at baseline before enalaprilat infusion, and repeatedly over 2 hours
      after the infusion. Enalaprilat infusion (median dose, 2.0 mg; infusion time, 48
      minutes) caused a significant decrease in pulmonary capillary wedge pressure (p =
      0.004), lasting until the end of the 2 hours' follow-up. This coincided with
      inhibition of serum angiotensin-converting enzyme activity (p < 0.001), an
      increase in plasma renin activity (p = 0.022), and decreases in plasma endothelin
      (p = 0.035), atrial natriuretic peptide (p = 0.005), and serum aldosterone (p =
      0.001) concentrations. Cardiac output, venous admixture, and oxygen delivery and
      consumption remained unchanged. CONCLUSIONS: Adding enalaprilat to conventional
      therapy makes it possible to unload the left ventricle and to relieve overt
      neurohormonal activation temporarily while maintaining cardiac function and
      systemic oxygenation.

PMID- 9263091
TI  - Topical ice slurry prevents brain rewarming during deep hypothermic circulatory
      arrest in newborn sheep.
AB  - OBJECTIVES: To measure the effect of ice slurry topical cooling on brain surface
      temperature during deep hypothermic circulatory arrest. DESIGN: This was a
      prospective, controlled experiment. SETTING: Animal laboratory at a university
      hospital. PARTICIPANTS: Five control lambs, five treatment (ice slurry) lambs.
      INTERVENTIONS: Animals were studied in two groups: the study group had topical
      cooling of the head with ice slurry started immediately before circulatory arrest
      and continued throughout the period of circulatory arrest; control group lambs
      received no supplemental topical cooling. MEASUREMENTS AND MAIN RESULTS: Brain
      surface temperature, scalp, nasopharyngeal, and rectal temperatures were measured
      at 5-minute intervals during 45 minutes of circulatory arrest. Lambs receiving
      topical cooling of the head with ice slurry had a statistically significant
      decrease in brain surface temperature of 2.2 +/- 1.2 degrees C during circulatory
      arrest, whereas brain surface temperature increased 1.2 +/- 0.3 degrees C, in
      control lambs. Equilibration of temperature between the scalp and brain in
      control lambs produced rewarming of the brain surface. CONCLUSIONS: Topical
      cooling of the head with ice slurry in newborn lambs lowers brain surface
      temperature during deep hypothermic circulatory arrest. Surrogate temperature
      monitoring locations such as nasopharyngeal and rectal temperatures varied
      significantly and do not accurately reflect changes in brain surface temperature.

PMID- 9263092
TI  - The effects of endobronchial cuff inflation on double-lumen endobronchial tube
      movement after lateral decubitus positioning.
AB  - OBJECT: This study was designed to measure changes in tracheal and bronchial
      lumen distances from mainstem and secondary carina with lateral positioning, and
      to assess whether inflation of the endobronchial cuff before lateral positioning
      would further secure a double-lumen endobronchial tube (DLT) and reduce movement.
      DESIGN: Prospective study. SETTING: University-affiliated cancer center.
      PARTICIPANTS: Fifty adult patients scheduled for elective thoracic surgical
      procedures requiring the placement of a left DLT. INTERVENTIONS: Patients were
      sequentially assigned to either the endobronchial cuff-inflated group or the
      deflated group during lateral positioning. After induction of general anesthesia,
      a left polyvinylchloride (PVC) DLT was placed and the position confirmed. In the
      supine position, the distance from the tip of the tracheal lumen to main carina
      was measured using a fiberoptic bronchoscope (FOB) passed through the tracheal
      lumen, and the distance from the bronchial lumen to secondary carina was measured
      with the FOB passed through the bronchial lumen. The patients were then
      positioned laterally and a second set of measurements taken. Overall movement was
      determined by increases and decreases in tracheal and bronchial distances
      obtained by substracting supine values from lateral values. MEASUREMENTS AND MAIN
      RESULTS: There was significant tracheal movement in 40 of 50 patients, with a
      mean of 0.92 +/- 1.0 cm. This was predominantly in the upward direction, as seen
      in 35 of 50 patients. There was significant bronchial movement in 37 of 50
      patients, with a mean of 0.92 +/- 1.15 cm. Also, predominance in the upward
      direction was seen in 34 of 50 patients. CONCLUSIONS: DLTs move with lateral
      positioning, regardless of endobronchial cuff inflation. The movement is
      predominantly in the upward direction. Therefore, fiberoptic visualization in the
      supine position should be used only to confirm that the endobronchial lumen is
      placed on the appropriate side and the cuff is at least 1 cm inside the left
      mainstem bronchus. Final positioning should always be verified in the lateral
      position.

PMID- 9263093
TI  - A comparison of two different bronchial cuff designs and four different bronchial
      cuff inflation methods.
AB  - OBJECTIVE: To compare directly measured pressures at the cuff/trachea interface
      that are associated with two different bronchial cuff designs and four different
      methods of bronchial cuff inflation suggested for use with one-lung ventilation.
      DESIGN: In vitro study. SETTING: Experimental laboratory in a university
      affiliated hospital. INTERVENTIONS: The bronchial cuffs of two different
      endotracheal tubes were inflated using one of four different methods of
      determining the cuff volume and pressure necessary to "just seal" the bronchus
      and obtain lung separation; positive-pressure test, negative-pressure test, CO2
      analysis, and a new test using an anesthesia ventilator. When each method
      predicted the "just-seal" state, the pressure at the cuff/bronchus interface as
      well as cuff inflation pressure and volume were recorded. MEASUREMENTS AND MAIN
      RESULTS: Although the new test was incompatible with the bronchial blocker, the
      other three tests all accurately predicted lung separation with the Univent, with
      no significant differences in pressures exerted on the trachea. However, when
      used with the double-lumen tube, the new test produced significantly lower
      measured parameters than the other inflation methods. CO2 analysis did not
      reliably predict bronchial seal with the double-lumen tube. CONCLUSIONS: To
      achieve lung separation with the lowest pressure on the trachea, the new test is
      the most appropriate method for use with the double-lumen tube; however, the
      negative-pressure test appeared to be the easiest and fastest method for use with
      the bronchial blocker. Although the bronchial blocker was associated with lower
      pressures transmitted from the cuff to the trachea, the in vitro model cannot
      predict which bronchial cuff design would be superior in vivo.

PMID- 9263094
TI  - Lung mechanical behavior during one-lung ventilation.
AB  - OBJECTIVE: Switching from two-lung to one-lung ventilation would be expected to
      have large effects on lung mechanical properties, and these effects may depend on
      tidal volume and respiratory frequency. These changes in lung mechanics with one
      lung ventilation may be similar to pulmonary edema. Deteriorating lung mechanics
      during pulmonary edema have been attributed to a loss of ventilated lung units.
      Therefore, changes in lung mechanics caused by one-lung ventilation were measured
      and compared with those previously seen during pulmonary edema. DESIGN:
      Prospective study. SETTING: Research laboratory. INTERVENTIONS: After induction
      of anesthesia, beagle dogs' tracheas were intubated with an endotracheal tube
      with a bronchial blocker (Univent System Corp, Tokyo, Japan) to apply one-lung
      ventilation. The proper position of the bronchial blocker during one-lung
      ventilation was confirmed with a fiberoptic bronchoscope. MEASUREMENTS AND MAIN
      RESULTS: Lung elastance (EL) and resistance (RL) were calculated from
      measurements of airway pressure, esophageal pressure, and airway flow in five
      anesthetized, paralyzed dogs during sinusoidal forcing at a constant mean airway
      pressure of 10 cmH2O in a wide range of breathing frequencies (0.2 to 1.0 Hz in
      intervals of 0.2) and tidal volumes (50, 100, 200, and to 300 mL). Measurements
      were made before and after the left mainstem bronchus was occluded with the
      bronchial blocker. During ventilation of both lungs, EL and RL depended
      relatively little on frequency, and both EL and RL were independent of tidal
      volume. During one-lung ventilation, EL doubled and, at most frequencies, RL
      increased; frequency dependences were not increased, and no dependence on tidal
      volume was observed. CONCLUSIONS: The lack of tidal volume dependence in EL and
      lack of large-frequency dependence in RL during one-lung ventilation are
      inconsistent with changes induced by severe pulmonary edema. Although decreases
      in ventilatable lung volume may contribute to increases in lung elastance, other
      characteristics of mechanical behavior during one-lung ventilation differ from
      those of pulmonary edema; therefore, other additional mechanisms must be involved
      in determining lung mechanical properties during severe pulmonary edema.

PMID- 9263096
TI  - Airway obstruction with a minitracheotomy tube.

PMID- 9263095
TI  - Chest wall and lung mechanics during acute hemorrhage in anesthetized dogs.
AB  - OBJECTIVES: In trauma and in surgical patients, respiratory mechanics may change
      because of many factors, including the hypotension induced by hemorrhage. The
      effects of acute hemorrhage on elastic and resistive characteristics of the
      respiratory system were studied. DESIGN: Prospective study. SETTING: Anesthesia
      research laboratory. INTERVENTIONS: Acute hemorrhagic shock was induced in 24
      supine anesthetized/paralyzed, mechanically ventilated dogs by blood withdrawal
      over a 12-minute period to decrease systolic arterial pressure to 50 mmHg;
      additional blood was subsequently withdrawn to maintain this pressure for 2
      hours. Total respiratory system dynamic compliance and resistance and lung and
      chest wall compliances and resistances were measured. MEASUREMENTS AND MAIN
      RESULTS: Total respiratory system dynamic compliance decreased from control (0.03
      +/- 0.002 L/cmH2O) by the first 10 minutes of shock (p < 0.05) and was 9.8 +/- 2%
      lower than control 2 hours after the induction of shock because of decreases in
      both lung (9.6 +/- 3%) and chest wall (7.7 +/- 3%) compliances. Total respiratory
      resistance increased 12.8 +/- 3% from control (3.08 +/- 0.19 cmH2O/L/s) after 2
      hours of shock (p < 0.05) because of an increase in chest wall resistance (21.6
      +/- 8%, p < 0.05). Pulmonary resistance was not significantly increased (p >
      0.05). In six control dogs, prepared similarly but not hemorrhaged, chest wall
      compliance and resistance did not change, but lung compliance gradually decreased
      by 17.8% during 150 minutes of anesthesia/paralysis. Lung resistance increased
      only after 100 minutes (p < 0.05). CONCLUSIONS: (1) Hemorrhagic shock caused
      slight changes in the chest wall, but effects on lung mechanics were a
      consequence of prolonged mechanical ventilation during anesthesia/paralysis, and
      (2) changes in respiratory mechanics caused by hemorrhagic shock are small and,
      unless other deleterious factors are present, would probably have little clinical
      significance.

PMID- 9263097
TI  - Mainstem bronchial intubation: an unrecognized source of hypotension during
      coronary artery bypass surgery.

PMID- 9263098
TI  - Intraoperative usefulness of transesophageal echocardiography: detection of
      unsuspected rupture of an aneurysm of the sinus of Valsalva.

PMID- 9263099
TI  - Anticoagulation for cardiopulmonary bypass of a patient with "heparin allergy".

PMID- 9263100
TI  - The MIDCAB experience: a current look at evolving surgical and anesthetic
      approaches.
AB  - This article reviews and updates the recent modifications in patient selection
      and revisions in the anesthetic approach to MIDCAB surgery. It outlines the
      changing surgical selection criteria, current ways to assess graft patency, and
      evolving anesthetic management. A promising new advancement in coronary artery
      bypass, the minimally invasive technique has received varying reviews and
      undergoes careful evaluation. Increasing surgical experience, immediate
      postoperative assessment of graft patency, and improvement in surgical
      instruments are expected to improve patient outcome. A stratification of MIDCAB
      patients into status I and status II patients will aid in future evaluation of
      surgical and anesthetic outcome. Communication of newly developed techniques to
      those caring for cardiovascular patients is imperative.

PMID- 9263101
TI  - A pathophysiological basis for informed preoperative smoking cessation
      counseling.

PMID- 9263103
TI  - Case 3--1997. Bilateral pulmonary edema after left modified Blalock-Taussing
      shunt.

PMID- 9263102
TI  - Electrophysiological mechanisms for ventricular arrhythmias in patients with
      myocardial ischemia: anesthesiologic considerations, Pt II.
AB  - This is the second half of a two-part review article that discusses ventricular
      tachyarrhythmias, either induced by acute ischemia or consequent to chronic
      myocardial ischemia, and their anesthestic implications. The first half of the
      article was published in the June 1997 Issue of The Journal.

PMID- 9263104
TI  - Mini-CABG: a step forward or backward? The "pro" point of view.

PMID- 9263105
TI  - Mini-CABG: a step forward or a step backward? the "con" point of view.

PMID- 9263106
TI  - Detection of an abnormal aortic valve by intraoperative transesophageal
      echocardiography.

PMID- 9263107
TI  - A knotty problem.

PMID- 9263108
TI  - Hemodynamic instability and excessive vasoconstrictor use during cardiopulmonary
      bypass.

PMID- 9263109
TI  - Avoiding neurological injury.

PMID- 9263110
TI  - A simple technique for contralateral left bronchial intubation in children
      undergoing right thoracotomy or thoracoscopy.

PMID- 9263111
TI  - Plateletapheresis with a next generation blood cell separator.
AB  - Procedure time has been identified as the-most important element in apheresis
      platelet donor retention. Fenwal has developed a next generation apheresis
      system, the Amicus, with the intent of efficiently producing high platelet yields
      with low WBC content in much shorter processing times than currently available.
      This report describes the Amicus and presents results of a clinical trial of an
      Amicus prototype and a comparison to Fenwal CS 3000+. Thirty Amicus double-needle
      plateletapheresis procedures were evaluated. Average processing time was 61 +/-
      16 min with 63% of the processing times < or = 60 min. The average preplatelet
      count was 246 +/- 46 x 10(3)/microliter, platelet yield 4.4 +/- 1.2 x 10(11) plt,
      collection efficiency 73 +/- 14%, platelet collection rate 0.075 +/- 0.016 plt x
      10(11)/min and citrate toxicity incidence 3%. A comparison of double-needle
      procedures, 20 Amicus and 20 CS 3000+, showed that Amicus had significantly
      shorter (P < .05) processing times (64 +/- 17 vs. 86 +/- 10 min) and higher (P <
      .05) platelet collection rates (0.070 +/- 0.017 vs. 0.054 +/- 0.018 plt x
      10(11)/min) but comparable (P < .05) platelet yields (4.4 +/- 1.4 vs. 4.7 +/- 1.0
      x 10(11) plt). Comparison of 13 single and 13 double-needle Amicus procedures
      showed comparable (P < .05) processing times (71 +/- 13 vs. 65 +/- 18 min),
      platelet yields (4.7 +/- 1.0 vs. 4.6 +/- 1.5 x 10(11) plt), collection efficiency
      (74 +/- 7 vs 74 +/- 17%), and platelet collection rates (0.068 +/- 0.020 vs 0.072
      +/- 0.018 plt x 10(11)/min). Using normal probability plots of WBC content at 95%
      confidence level. Amicus can provide products with < 5.0 x 10(6)WBC or < 1.0 x
      10(6) WBC in 99.7% or 92.7% of collections, respectively, compared with 69.0% or
      44.0%, respectively, for CS 3000+. We found Amicus was able to provide equivalent
      quantities of platelets with less WBC content in significantly shorter processing
      times than CS3000+ as well as shown encouraging results for single-needle
      procedures.

PMID- 9263112
TI  - Prospective, concurrent comparison of the Cobe Spectra and Haemonetics MCS-3P
      cell separators for leukapheresis after high-dose filgrastim in patients with
      hematologic malignancies.
AB  - A prospective study was undertaken to compare the mononuclear cell, CD34+ cell,
      and CFU-GM yields of the Haemonetics MCS-3P and the Cobe Spectra cell separators
      in ten patients (nine multiple myeloma and one non-Hodgkin lymphoma) on two
      consecutive days after mobilization with high-dose filgrastim (12-16
      micrograms/k) for 4 days. All patients were harvested once on each machine, five
      starting on each machine. The target duration of the procedure on the Spectra was
      160 minutes, and the target blood volume processed on the MCS-3P was 60-70 ml/kg
      body weight. Both machines were operating on the 1995 software versions supplied
      by the respective manufacturers. The time taken for the procedure was
      significantly longer with the Haemonetics machine. The volumes of blood processed
      and the product collected were significantly higher with the Spectra, as were the
      absolute mononuclear and CD34+ cell yields, and yields per unit time. Mononuclear
      and CD34+ cell yields per unit volume of blood processed were comparable for both
      machines. The differences in CFU-GM yields were not significant, largely because
      of wide interpatient variations. The extent of platelet depletion as a result of
      the procedure was greater with the Spectra because of the higher blood volume
      being processed. We conclude that the Cobe Spectra is a significantly faster
      machine than the Haemonetics MCS-3P; and consequently, its use is associated with
      higher mononuclear and CD34+ cell yields.

PMID- 9263113
TI  - Adjustment of the interface detector (location 71) to the absolute number of
      mononuclear cells in the peripheral blood: no improvement of the collection
      efficiency of the Fenwal CS3000 plus during progenitor cell harvests.
AB  - Improvement of the collection efficiency (CE) of the Fenwal CS3000 plus in
      collecting circulating progenitor cells (CPC) might diminish the number of
      leukapheresis procedures (LP) required to obtain the CPC required to assure
      engraftment. We analyzed whether adjustment of the optical setting (location
      71,L71) to the number of MNC present in the peripheral blood could enhance the CE
      of the MNC. Thirty-five patients underwent 121 LP with an adjusted L71. We
      compared the results retrospectively with 26 LP performed with a fixed L71
      (1:100) in 12 patients. The CPC were mobilized with chemotherapy followed by
      subcutaneous administration of granulocyte colony-stimulating factor (G-CSF) in
      both groups. Adjustment of the L71 did neither improve the CE of the MNC, the
      estimated CE of CD34+ cells nor diminished granulocyte contamination. For the
      total 121 LP with an adjusted L71 and for the total 26 LP with a fixed L71 the
      mean CE of MNC were, respectively, 44.6 +/- 18.3% and 46.4 +/- 14%. The mean
      granulocyte contamination, determined by manual white blood cell differentiation,
      was 1.7 +/- 2.3% for the adjusted L71 group and 2.3 +/- 3 for the fixed L71
      group. There was no difference in the median number of LP required to obtain 3 x
      10(6) CD34+ cells/kg between both groups. We found a weak significant correlation
      between WBC and pre-LP MNC count and the CE of MNC (r = 0.36, P = 0.012, resp.r =
      0.33, P = 0.023), but no correlation between the CE of MNC and the estimated CE
      of CD34+ cells (r = 0.24, P = 0.113). In conclusion, adjustment of the L71 to the
      MNC did not improve the CE of MNC of the Fenwal CS3000. The lack of correlation
      between the CE and MNC and the estimated CE of CD34+ cells should be further
      explored.

PMID- 9263114
TI  - Determinants of the efficacy of prophylactic granulocyte transfusions: a meta
      analysis.
AB  - BACKGROUND: Cytokines that improve granulocyte collection yields have recently
      become available, and may lead to a new series of trials of granulocyte
      transfusion (GTX) therapy. We conducted a meta-analysis of studies of
      prophylactic GTX in order to identify the determinants of efficacy of this
      intervention, and to assist in the design of future trials of GTX for the
      treatment of patients with overwhelming infection. METHODS: Randomized controlled
      trials of the efficacy of prophylactic GTX published in English in 1970-1995 were
      retrieved, and eight studies were eligible for analysis. Summary relative odds
      (RR) of bacterial or fungal infection, death, or death from infection in
      transfused patients vs. controls were computed for patient subsets defined on the
      basis of dose of granulocytes transfused, assessment of leukocyte compatibility,
      duration of neutropenia, and infection rate of controls. The random-effects
      method was used for all analyses. RESULTS: Assessment of leukocyte compatibility
      prior to the transfusion, dose of granulocytes transfused, and duration of
      neutropenia in enrolled patients could account, respectively, for the variation
      in findings across published reports in terms of all three, two, and one of the
      outcome measures studied. Transfusion of adequate doses of compatible leukocytes
      significantly reduced the relative risk (RR) of infection, death, and death from
      infection in transfused patients vs. controls (RR = 0.075, RR = 0.224, and RR =
      0.168, respectively; P < 0.05). CONCLUSION: Two necessary elements in the design
      of future trials of therapeutic GTX should be the transfusion of high doses of
      granulocytes and the provision of leukocytes that are crossmatch-compatible with
      the recipient's serum.

PMID- 9263115
TI  - Evaluation of a new protocol for peripheral blood stem cell collection with the
      Fresenius AS 104 cell separator.
AB  - In this report we analyzed sixty leukapheresis procedures on 35 patients with a
      new protocol for the Fresenius AS 104. Yields and efficiencies for MNC, CD 34+
      cells, and CFU-GM indicate that the new protocol is able to collect large
      quantities of hemopoietic progenitors. Procedures were performed processing 8.69
      +/- 2.8 liters of whole blood per apheresis and modifying 3 parameters: spillover
      volume 7 ml, buffy-coat volume 11.5 ml, centrifuge speed 1,500 rpm; blood flow
      rate was 50 ml/min and the anticoagulant ratio was 1:12. No side effects were
      observed during apheresis procedures except for transient paresthesia episodes
      promptly resolved with the administration of calcium gluconate. Yields show a
      high capacity of the new program to collect on average MNC 17.28 +/- 10.85 x
      10(9), CD 34+ 471 +/- 553.5 x 10(6) and CFU-GM 1278.7 +/- 1346.3 x 10(4) per
      procedure. Separator collection efficiency on average was 49.91 +/- 23.28% for
      MNC, 55.1 +/- 35.66% for CFU-GM, and 62.97 +/- 23.09% for CD 34+ cells.
      Particularly interesting are results for MNC yields and CD 34+ efficiency; these
      results make the new program advantageous or similar to the most progressive
      blood cell separators and capable to collect a sufficient number of progenitor
      cells for a graft with a mean of 1.80 +/- 0.98 procedures per patient.

PMID- 9263116
TI  - Partial colloid starch replacement for therapeutic plasma exchange.
AB  - Traditionally protein solutions have been used as the replacement solution of
      choice during therapeutic plasma exchange (TPE). Treatment protocols vary, but
      neurology patients, who exhibit autonomic instability, are typically replaced
      entirely with 5% protein solution. Due to sporadic product shortages and the
      increasing cost of protein solutions, we evaluated the use of 6% and 3%
      hetastarch (HES) as partial replacement during TPE. All adult neurology patients
      with normal liver, heart, and kidney function were evaluated for HES replacement.
      The first seven patients (33 procedures) received 1000 ml of 6% hetastarch as
      part of their replacement fluid and the next 42 patients (289 procedures)
      received 1000 ml of 3% HES as part of their replacement fluid. Three patients
      crossed over into both groups. Patients were evaluated for signs of peripheral
      edema, evidence of bleeding, skin rash, and any subjective changes. Total protein
      albumin, osmolality, PT, and aPTT were measured prior to each procedure in the
      first five patients in each group. In both groups there was a drop in total
      protein, but all other lab values returned to normal limits within 48 hours of
      treatment. One patient reported slight peripheral edema after two procedures. In
      the 3% HES group the BP and P remained stable in 97.3% (280) procedures. Two
      patients receiving 6% HES and 1 patient receiving 3% HES complained of severe
      transient back and head pain during HES infusion. There was no evidence of
      bleeding or subjective changes. Three percent HES is a safe and cost-effective
      partial replacement for albumin during TPE.

PMID- 9263117
TI  - Sepsis and polyspecific intravenous immunoglobulins.
AB  - The treatment of sepsis with i.v. immunoglobulins (IVIG) is currently regarded as
      not indicated. Several clinical studies, placebo controlled since 1985, to
      determine efficacy have failed to prevent fatal outcome, even when IVIG was given
      at high doses. The prevailing action mechanism put forward by most researchers is
      the capacity of specific antibodies contained in IVIG to bind to the infectious
      organism followed by opsonophagocytosis. Recently, IVIG preparations have been
      shown, both in vitro and in vivo, to profoundly affect the homeostasis of the
      cytokine network, probably in a way which directs this network from disturbed to
      regulated functioning. Excessive production and insufficient removal of cytokines
      due to multiorgan failure of sepsis patients are now known to play a decisive
      role in progression of sepsis to septic shock. There are researchers wondering
      whether the newly discovered influence of IVIG on cytokines might not be
      exploited for the design of improved study protocols, including better selection
      of the dosage, dosage schedule, association to other treatments and selection of
      patients. On the side of the IVIG preparations, improvements discussed include
      spiking of polyclonal preparations with monoclonal antibodies, selection of
      appropriate production lots and study of the efficacy not only of IgG but also of
      IgM isotype containing preparations.

PMID- 9263118
TI  - Allogeneic peripheral blood stem cell transfusion from human leukocyte antigen
      mismatched sibling for the treatment of engraftment failure after bone marrow
      transplantation for severe aplastic anemia.

PMID- 9263119
TI  - Contamination of Bacillus cereus in an apheresis-derived platelet concentrate.

PMID- 9263120
TI  - Proton nuclear magnetic resonance studies on huwentoxin-I from the venom of the
      spider Selenocosmia huwena: 2. Three-dimensional structure in solution.
AB  - The three-dimensional structure in aqueous solution of native huwentoxin-I, a
      neurotoxin from the venom of the spider Selenocosmia huwena, has been determined
      from two-dimensional H NMR data recorded at 500 and 600 MHz. Structural
      constraints consisting of interproton distances inferred from NOEs and dihedral
      angles from spin-spin coupling constants were used as input for distance geometry
      calculation with the program XPLOR 3.1. The best 10 structures have NOE
      violations < 0.3 A, dihedral violations < 2 degrees, and pairwise root-mean
      square differences of 1.08 (+/- 0.20) A over backbone atoms (N, C alpha, C). The
      molecule adopts a compact structure consisting of a small triple-stranded
      antiparallel beta-sheet and five beta-turns. A small hydrophobic patch consisting
      of Phe 6, Trp 28, and Trp 31 is located on one side of the molecule. All six
      lysine residues are distributed on the molecular surface. The three disulfide
      bridges are buried within the molecule. The structure contains an "inhibitor
      cystine knot motif" which is adopted by several other small proteins, such as
      omega-conotoxin, agatoxin IVA, and gurmarin.

PMID- 9263121
TI  - Classification and prediction of beta-turn types.
AB  - Although a beta-turn consists of only four amino acids, it assumes many different
      types in proteins. Is this basically dependent on the tetrapeptide sequence alone
      or is it due to a variety of interactions with the other part of a protein? To
      answer this question, a residue-coupled model is proposed that can reflect the
      sequence-coupling effect for a tetrapeptide in not only a beta-turn or non-beta
      turn, but also different types of a beta-turn. The predicted results by the model
      for 6022 tetrapeptides indicate that the rates of correct prediction for beta
      turn types I, I', II, II', VI, and VIII and non-beta-turns are 68.54%, 93.60%,
      85.19%, 97.75%, 100%, 88.75%, and 61.02%, respectively. Each of these seven rates
      is significantly higher than 1/7 = 14.29%, the completely randomized rate,
      implying that the formation of different beta-turn types or non-beta-turns is
      considerably correlated with the sequences of a tetrapeptide.

PMID- 9263122
TI  - A computer modeling study of the interaction between tissue factor pathway
      inhibitor and blood coagulation factor Xa.
AB  - Activation of blood coagulation factor X to factor Xa (FXa) is inhibited by
      tissue factor pathway inhibitor (TFPI). The second Kunitz-type inhibitory domain
      (K2) of TFPI binds a catalytic domain of FXa, whereas the first domain (K1) does
      not. We analyzed computer models of complexes of FXa with K1 or K2, which were
      made using a crystal structure of FXa. Favorable hydrophobic interaction was
      observed in the complex of FXa with K2. Furthermore, we constructed a tertiary
      structure of FXa using CHIMERA to assess the accuracy of a homology modeling
      method. The isolated model structure of FXa agreed well with the crystal
      structure, but analyses of complexes of this structure with K1 or K2 revealed
      that the models of complexes could not provide clear evidence of greater binding
      ability to K2 because of the positional difference of a few side chains
      interacting with the inhibitor.

PMID- 9263123
TI  - Predicting differential antigen-antibody contact regions based on solvent
      accessibility.
AB  - A novel computational approach was examined for predicting epitopes from primary
      structures of the seven immunologically distinct botulinum neurotoxins (BoNT/A-G)
      and tetanus toxin (TeTX). An artificial neural network [Rost and Sander (1994),
      Proteins 20, 216] was used to estimate residue solvent accessibilities in
      multiple aligned sequences. A similar network trained to predict secondary
      structures was also used to examine this protein family, whose tertiary fold is
      presently unknown. The algorithm was validated by showing that it was 80%
      accurate in determining the secondary structure of avian egg-white lysozyme and
      that it correctly identified highly solvent-exposed residues that correspond to
      the major contact regions of lysozyme-antibody cocrystals. When sequences of the
      heavy (H) chains of TeTX and BoNT/A-G were analyzed, this algorithm predicted
      that the most highly exposed regions were clustered at the sequentially
      nonconserved N- and C-termini [Lebeda and Olson (1994), Proteins 20, 293]. The
      secondary structures and the remaining highly solvent-accessible regions were, in
      contrast, predicted to be conserved. In experiments reported by others, H-chain
      fragments that induced immunological protection against BoNT/A overlap with these
      predicted most highly exposed regions. It is also known that the C-terminal
      halves of the TeTX and BoNT/A H-chains interfere with holotoxin binding to
      ectoacceptors on nerve endings. Thus, the present results provide a theoretical
      framework for predicting the sites that could assist in the development of
      genetically engineered vaccines and that could interact with neurally located
      toxin ectoacceptors. Finally, because the most highly solvent-exposed regions
      were not well conserved, it is hypothesized that nonconserved, potential contact
      sites partially account for the existence of different dominant binding regions
      for type-specific neutralizing antibodies.

PMID- 9263124
TI  - Molecular dynamics on complexes of ras-p21 and its inhibitor protein, rap-1A,
      bound to the ras-binding domain of the raf-p74 protein: identification of
      effector domains in the raf protein.
AB  - We have computed the average structures for the ras-p21 protein and its strongly
      homologous inhibitor protein, rap-1A, bound to the ras-binding domain (RBD) of
      the raf protein, using molecular dynamics. Our purpose is to determine the
      differences in structure between these complexes that would result in no
      mitogenic activity of rap-1A-RBD but full activity of p21-RBD. We find that
      despite the similarities of the starting structures for both complexes, the
      average structures differ considerably, indicating that these two proteins do not
      interact in the same way with this vital target protein. p21 does not undergo
      major changes in conformation when bound to the RBD, while rap-1A undergoes
      significant changes in structure on binding to the RBD, especially in the
      critical region around residue 61. The p21 and rap-1A make substantially
      different contacts with the RBD. For example, the loop region from residues 55-71
      of rap-1a makes extensive hydrogen-bond contacts with the RBD, while the same
      residues of p21 do not. Comparison of the structures of the RBD in both complexes
      reveals that it undergoes considerable changes in structure when its structure
      bond to p21 is compared with that bound to rap-1A. These changes in structure are
      due to displacements of regular structure (e.g., alpha-helices and beta-sheets)
      rather than to changes in the specific conformations of the segments themselves.
      Three regions of the RBD have been found to differ significantly from one another
      in the two complexes: the binding interface between the two proteins at residues
      60 and 70, the region around residues 105-106, and 118-120. These regions may
      constitute effector domains of the RBD whose conformations determine whether or
      not mitogenic signal transduction will occur.

PMID- 9263125
TI  - Inhibition of oncogenic and activated wild-type ras-p21 protein-induced oocyte
      maturation by peptides from the ras-binding domain of the raf-p74 protein,
      identified from molecular dynamics calculations.
AB  - In the preceding paper we found from molecular dynamics calculations that the
      structure of the ras-binding domain (RBD) of raf changes predominantly in three
      regions depending upon whether it binds to ras-p21 or to its inhibitor protein,
      rap-1A. These three regions of the RBD involve residues from the protein-protein
      interaction interface, e.g., between residues 60 and 72, residues 97-110, and 111
      121. Since the rap-1A-RBD complex is inactive, these three regions are implicated
      in ras-p21-induced activation of raf. We have therefore co-microinjected peptides
      corresponding to these three regions, 62-76, 97-110, and 111-121, into oocytes
      with oncogenic p21 and microinjected them into oocytes incubated in in insulin,
      which activates normal p21. All three peptides, but not a control peptide,
      strongly inhibit both oncogenic p21- and insulin-induced oocyte maturation. These
      findings corroborate our conclusions from the theoretical results that these
      three regions constitute raf effector domains. Since the 97-110 peptide is the
      strongest inhibitor of oncogenic p21, while the 111-121 peptide is the strongest
      inhibitor of insulin-induced oocyte maturation, the possibility exists that
      oncogenic and activated normal p21 proteins interact differently with the RBD of
      raf.

PMID- 9263126
TI  - Expression, purification, characterization, and X-ray analysis of
      selenomethionine 215 variant of leukocyte collagenase.
AB  - Matrix metalloproteinases belong to the superfamily of metzincins containing,
      besides a similar topology and a strictly conserved zinc environment, a 1,4-tight
      turn with a strictly conserved methionine residue at position three (the so
      called Met-turn [Bode et. al. (1993) FEBS 331, 134-140; Stocker et al. (1995)
      Protein Sci. 4, 823-840]. The distal S-CH3 moiety of this methionine residue
      forms the hydrophobic basement of the three His residues liganding the catalytic
      zinc ion. To assess the importance of this methionine, we have expressed the
      catalytic domain of neutrophil collagenase (rHNC, residues Met80-Gly242) in the
      methionine auxotrophic Escherichia coli strain B834[DE3](hsd metB), with the two
      methionine residues replaced by selenomethionine. Complete replacement was
      confirmed by amino acid analysis and electrospray mass spectrometry. The folded
      and purified enzyme retained its catalytic activity, but showed modifications
      which are reflected in change kinetic parameters. The Met215SeMet substitution
      caused a decrease in conformational stability upon area denaturation. The X-ray
      crystal structure of this selenomethionine rHNC was virtually identical to that
      of the wild-type catalytic domain except for a very faint local disturbance
      around the sulfur-seleno substitution site.

PMID- 9263127
TI  - Inhibition of tryptase TL2 from human T4+ lymphocytes and inhibition of HIV-1
      replication in H9 cells by recombinant aprotinin and bikunin homologues.
AB  - The serine esterase TL2 from human T4+ lymphocytes is a binding component to HIV
      1 glycoprotein gp120 and seems to play a role in the HIV-1 infection mechanism.
      Recombinant variants of the Kunitz-type serine proteinase inhibitor aprotinin
      were investigated for their ability to inhibit tryptase TL2 and the binding of
      gp120 to this enzyme. Furthermore, the viral replication of HIV-1 was
      investigated H9 cell cultures under the influence of recombinant aprotinin and
      bikunin variants. In contrast to native aprotinin, the recombinant variant
      [Arg15, Phe17, Glu52] aprotinin with a reactive-site sequence homologous to the
      V3 loop of HIV-1 gp120 showed a specific inhibition of tryptase TL2 (> 80%).
      However, the [Leu15, Phe17, Glu52] aprotinin variant with hydrophobic subsites
      was the most potent inhibitor of the binding of gp120 to tryptase TL2 (68%). Our
      results show that the enzyme activity of purified tryptase TL2 is inhibited not
      only by variants with basic amino acids, but also those with hydrophobic residues
      in the reactive-site region. Therefore, tryptase TL2 is not a typical trypsin
      like or chymotrypsin-like protease. Investigations on inhibition of HIV-1
      replication in H9 cell cultures showed that tryptase TL2 is involved in the
      mechanism of virus internalization into human lymphocytes. The [Leu15, Phe17,
      Glu52] aprotinin showed a significant retardation of syncytium formation over a
      period of 5 days in a 1 micro M concentration. Similar investigations were
      performed with recombinant variants of bikunin, the light chain of human inter
      alpha-trypsin inhibitor. Only the single-headed variant [Arg94] delta 2 bikunin
      inhibited slightly the syncytium formation over a period of 2 days in a 2.2 micro
      M concentration. Wild-type bikunin and all full-length variants showed no effect,
      possibly due to steric hindrance by the second domain of the double-headed
      inhibitor.

PMID- 9263128
TI  - Hospital communication threats and intervention.
AB  - 1. Threats are indirect acts of criminal behavior designed to weaken or injure
      individuals, institutions, or property. 2. All threats should be analyzed and
      investigated quickly and with high priority. 3. An interdisciplinary hospital
      team should conduct periodic reviews of threats received, threat management, and
      case outcome.

PMID- 9263129
TI  - Visual coping scenarios to facilitate discussion of coping responses with
      impoverished women at risk for AIDS.
AB  - 1. Impoverished and homeless women are prone to coping with life stresses through
      drug and alcohol use. 2. Visual coping scenarios are culturally sensitive
      strategies to help impoverished minority women discuss effective coping
      responses. 3. A visual coping scenario redirects attention from a negative
      emotional event to an effective problem-focused coping strategy.

PMID- 9263130
TI  - Consultation-liaison psychiatric nursing in long-term care.
AB  - 1. The psychiatric and mental health APRN is in an excellent position to use his
      or her training and expertise to integrate various models of care. 2. Clinical
      functions of the psychiatric and mental health APRN include patient-focused and
      staff-centered activities, administrative functions include consulting,
      performance improvement, and research. 3. The psychiatric and mental health APRN
      is well-equipped to adapt to developing changes and challenges in the future of
      long-term care.

PMID- 9263131
TI  - A hermeneutic analysis of the process of conducting clinical interviews.
AB  - 1. Although no right way to interview exists, an interviewer should develop a
      comfortable, personal style. 2. Allowing an interview to follow its own course
      while remembering the overall interview agenda will contribute to quality of the
      data. 3. Interviewing skills are enhanced as the interviewer develops a personal
      style and becomes comfortable as a practitioner.

PMID- 9263132
TI  - Stress intervention. A model of stress inoculation training.
AB  - 1. The initial clinical experience in a hospital setting has been identified as a
      major area of threat for beginning nursing students. 2. A stress inoculation
      program, in which students were exposed to situation similar to future clinical
      experience, was used to help students develop confidence and coping skills. 3.
      The program was found to be an effective preparation for clinical experience,
      mainly in terms of the students clinical performance.

PMID- 9263133
TI  - Monitoring for methotrexate hepatotoxicity in patients with rheumatoid arthritis:
      another hepatologist's perspective.

PMID- 9263134
TI  - Sex hormones in systemic lupus erythematosus: a controversy for modern times.

PMID- 9263135
TI  - Understanding rheumatoid arthritis.

PMID- 9263136
TI  - Effects of tenidap and nonsteroidal antiinflammatory drugs on the response of
      cultured human T cells to interleukin 2 in rheumatoid arthritis.
AB  - OBJECTIVE: To assess the effects of tenidap, a new oxindole class
      antiinflammatory compound, on the proliferative response of cultured T cells to
      interleukin 2 (IL-2); and to compare these effects with the antiinflammatory
      drugs ibuprofen, naproxen, indomethacin, piroxicam, and sulindac. METHODS: T
      cells were cultured with either tenidap, ibuprofen, indomethacin, naproxen,
      piroxicam, or sulindac in the presence of IL-2, then assayed for incorporation of
      tritiated thymidine. RESULTS: Tenidap, ibuprofen, and naproxen, at
      therapeutically attainable concentrations, significantly inhibited the
      proliferative response of T cells to IL-2. In contrast, indomethacin, piroxicam,
      and sulindac did not alter this response. Tenidap had a direct inhibitory effect
      on the response of activated T cells to IL-2. Both ibuprofen and naproxen
      interfered with the binding of IL-2 to T cells. CONCLUSION: These results suggest
      variable effects of different antiinflammatory drugs on lymphocyte function that
      may relate to the differential effectiveness of these drugs in patients with
      rheumatoid arthritis.

PMID- 9263137
TI  - In vitro modulation of cytokine, cytokine inhibitor, and prostaglandin E release
      from blood mononuclear cells and synovial fibroblasts by antirheumatic drugs.
AB  - OBJECTIVE: To assess the effect of various antirheumatic drugs on cytokine,
      cytokine inhibitor, and prostaglandin E (PGE) production by normal blood
      mononuclear cells (MNC) and rheumatoid arthritis (RA) synovial fibroblasts in
      vitro. METHODS: MNC from healthy donors and RA synovial fibroblasts were
      preincubated with or without prostaglandin E2 (PGE2), indomethacin,
      dexamethasone, gold sodium thiomalate (GSTM), methotrexate (MTX), and cyclosporin
      A (CyA), and then cultured in the absence or presence of interleukin-1 beta (IL-1
      beta) or tumor necrosis factor-alpha (TNF-alpha) for 48 h. We characterized
      cytokines such as IL-1 beta, IL-8, monocyte chemoattractant protein-1 (MCP-1),
      and cytokine inhibitors such as IL-1 receptor antagonist (IL-1ra) and soluble TNF
      receptors (sTNFR p55 + p75) as well as PGE in the cell-free culture supernatants.
      RESULTS: In MNC and synovial fibroblast cultures dexamethasone, GSTM, and PGE2
      most markedly downregulated spontaneous and/or cytokine stimulated production of
      IL-1 beta, IL-14a, IL-8, and MCP-1, whereas sTNFR shedding was not affected. In
      contrast, MTX and CyA had only marginal or no effects on mediator release,
      whereas indomethacin inhibited only PGE production. CONCLUSION: Among several
      antirheumatic drugs examined, dexamethasone and GSTM exhibited the most potent
      inhibitory effects on inflammatory cytokine and cytokine inhibitor production by
      blood mononuclear cells and synovial fibroblasts. These drugs may exert their
      antiinflammatory actions by unspecific suppression of monocyte and fibroblast
      secretory function.

PMID- 9263138
TI  - Comparative usefulness of C-reactive protein and erythrocyte sedimentation rate
      in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To determine the comparative usefulness of the C-reactive protein
      (CRP) and erythrocyte sedimentation rate (ESR) in the assessment of rheumatoid
      arthritis (RA) activity and to provide tables and nomograms of normative data in
      RA allowing the linking and interchange of test values. METHODS: We studied 774
      patients with RA seen in the clinic by obtaining complete rheumatologic
      examinations and laboratory studies. Clinical variables included visual analog
      scale pain and global severity, joint count, functional disability, depression,
      and a composite measure of disease activity. In addition, we measured ESR and
      hemoglobin, and rheumatoid factor (RF), CRP, IgG, IgA, IgM, haptoglobin, alpha 1
      antitrypsin, albumin, pre-albumin, and C4 by nephelometry. RESULTS: Median values
      for CRP were 0.82 mg/dl and ESR 26 mm/h. The average correlation with 7 clinical
      variables was 0.248 for ESR compared to 0.259 for CRP. But partial correlation
      analysis showed that a substantial portion of the correlation with ESR is
      explained by the effect of immunoglobulins, RF, and hemoglobin rather than the
      acute phase response. Twenty-eight percent of results were discordant between ESR
      and CRP, and this discordance was explained by the above factors. When
      discordance occurred, CRP was a better measure of disease activity than ESR.
      CONCLUSION: Simple comparisons between ESR and CRP suggest that both tests are
      similar, but partial correlation analysis indicates that part of the correlation
      between ESR and clinical variables comes from non-acute phase factors. These
      factors, in turn, are responsible for most of the discordance between ESR and CRP
      results. Thus, CRP appears to be the better test regarding measurement of the
      acute phase. Because ESR is sensitive to immunoglobulins and RF, it may measure
      general severity better than CRP, even though it is a poorer measure of
      inflammation. This perhaps accounts for the relative equivalence of the tests.
      The combination of ESR and CRP yields useful information that is often not
      apparent when only a single test is used.

PMID- 9263139
TI  - The C-reactive protein but not erythrocyte sedimentation rate is associated with
      clinical severity in patients with osteoarthritis of the knee or hip.
AB  - OBJECTIVE: To investigate the association of C-reactive protein (CRP) with
      symptoms of clinical disease and demographic factors in osteoarthritis (OA). In
      addition, to compare CRP with erythrocyte sedimentation rate (ESR) in their
      ability to associate with osteoarthritic symptoms and features. METHODS: A total
      of 655 consecutive clinic patients with OA of the knee or hip underwent a
      rheumatic disease examination, completed a clinical health assessment
      questionnaire (CLINHAQ), and had laboratory tests performed, including
      hemoglobin, CRP, and ESR. RESULTS: The median value of CRP was 5.9 micrograms/ml.
      CRP was significantly associated with functional disability, joint tenderness,
      pain, fatigue, global severity, and depression. In addition, correlations were
      noted for body mass index (BMI) and sex. ESR, by contrast, was unassociated with
      clinical signs or symptoms except for a weak association with functional
      disability. The best explanatory multiple regression model for CRP in OA includes
      BMI, functional disability, and joint tenderness count (R-squared 0.159).
      CONCLUSION: CRP is elevated in OA compared to healthy individuals, and is
      correlated with rheumatic disease signs and symptoms, including HAQ disability,
      joint count, and pain. The associations, not seen with ESR, appear to be real,
      but are not strong. An inflammatory component associated with OA can be detected
      in the serum.

PMID- 9263141
TI  - Limited bone loss due to corticosteroids; a systematic review of prospective
      studies in rheumatoid arthritis and other diseases.
AB  - OBJECTIVE: To clarify the relation between changes in bone density, the treated
      disease, and dose of corticosteroids prescribed. METHODS: MEDLINE database (1966
      95) and bibliographic searches selected cohorts of patients with rheumatoid
      arthritis (RA) and non-RA patients, studied by reliable serial bone density
      measurements. RESULTS: Two randomized controlled trials in early RA found greater
      lumbar bone loss after corticosteroid treatment (pooled effect size at 6 mo 3.9%;
      95% CI: 1.9, 6.0%). The other studies included 66 patients with RA taking mean 7
      mg prednisone/day; 371 "untreated" RA patients; and 216 non-RA patients taking
      mean 20 mg prednisone/day. Lumbar bone mass changed (weighted mean) 0.0% (-0.6,
      0.7%) per year in steroid treated RA, -0.6% (-0.9, -0.2%) in untreated RA, and 
      4.7% (-5.2, -4.3%) in non-RA. Femoral neck changed -3.0% (-4.2, -1.8%), -0.7% (
      1.0, -0.3%), and -1.5% (-2.5, -0.4%), respectively. In RA, most bone was lost in
      the first half year, and in early or uncontrolled disease. CONCLUSION: In
      patients with RA bone loss is limited, influenced by the interaction of disease
      characteristics and low dose corticosteroid therapy. In contrast, non-RA patients
      taking higher doses of corticosteriods may loss clinically relevant amounts of
      bone (i.e., > 5%) within one year.

PMID- 9263140
TI  - Effects of low dose methotrexate on the bone mineral density of patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: To determine the effects of low dose methotrexate (MTX) on bone
      mineral density (BMD) of patients with rheumatoid arthritis (RA). METHODS: We
      examined the relationship between BMD and disease modifying antirheumatic drug
      (DMARD) use with data from a prospective, randomized, placebo controlled trial
      assessing the effects of calcium and vitamin D3 supplementation on BMD of
      patients with RA. Measurements of BMD of the lumbar spine and femoral neck were
      performed at baseline and at yearly followup visits over 3 years. RESULTS:
      Information about DMARD use and BMD was available for 133 patients at baseline,
      and for 95 patients at Year 3. Lumbar spine and femoral neck BMD of MTX and non
      MTX treated patients were similar at the start of the study. At the end of 3
      years of followup, there was no significant differences in the change in BMD of
      the femoral neck and lumbar spine in MTX and non-MTX treated patients, in
      general. However, patients treated with prednisone > or = 5 mg/day plus MTX had
      greater loss of BMD in the lumbar spine than patients treated with a similar dose
      of prednisone without MTX (difference -8.08% over 3 years; p = 0.004).
      CONCLUSION: At the end of 3 years, low dose MTX use was not associated with
      change in femoral neck or lumbar spine BMD in patients who were not treated with
      corticosteroids. However, among patients treated with prednisone > or = 5 mg/day,
      combined treatment with MTX and prednisone was associated with greater bone loss
      in the lumbar spine than treatment with prednisone without MTX.

PMID- 9263142
TI  - Elevated levels of inflammatory cytokines in bone marrow of patients with
      rheumatoid arthritis and anemia of chronic disease.
AB  - OBJECTIVE: Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha)
      and interleukin 6 (IL-6) play an important role in decreased erythropoiesis in
      patients with anemia of chronic disease (ACD) and rheumatoid arthritis (RA).
      Modulation of quantities of bone marrow erythroid progenitors during chronic
      inflammation may be one of the pathogenetic mechanisms leading to ACD. We studied
      bone marrow from patients with ACD with RA by investigating, first, local
      production of inflammatory cytokines in the bone marrow, and second, the relative
      fraction of late erythroid progenitors (erythropoietin and transferrin receptor
      positive cells; EpoR+ TrfR+) in bone marrow. In addition, the effects of TNF
      alpha on EpoR+ TrfR+ cells were studied in vitro. METHODS: Levels of IL-6 and TNF
      alpha were measured by EL ELISA in supernatant of bone marrow and peripheral
      blood cultures from 14 patients with RA and ACD and 14 patients with RA without
      anemia. The numbers of EpoR+ TrfR+ cells in bone marrow samples of both groups
      were assessed by 2 color fluorescence flow cytometry. RESULTS: Levels of IL-6 and
      TNF-alpha were significantly higher in the supernatant of bone marrow cultures of
      patients with ACD compared to controls. No significant differences in the
      fraction of EpoR+ TrfR+ cells in samples was observed between the 2 groups of
      patients. Incubation of the samples with TNF-alpha did not result in modulation
      of the number of EpoR+ TrfR+ cells. CONCLUSION: Local production of
      proinflammatory cytokines in the bone marrow may be associated with the
      development of ACD in RA.

PMID- 9263144
TI  - Detection of large macrophage colony forming cells in the peripheral blood of
      patients with rheumatoid arthritis.
AB  - OBJECTIVE: To test for the presence of colony forming cells, that form large
      macrophage colonies (> 2.5 mm in diameter, > 10,000 cells), in the peripheral
      blood of patients with rheumatoid arthritis (RA) and to determine its association
      with the clinical and laboratory features of RA. METHODS: Peripheral blood
      mononuclear cells (PBMC) from 96 patients with RA and 20 healthy controls were
      assayed for in vitro colony formation. In addition, PBMC from 38 patients with
      other rheumatic diseases including systemic lupus erythematosus (SLE),
      progressive systemic sclerosis (SSc), and polymyositis/dermatomyositis (PM/DM);
      23 patients with infectious inflammatory diseases were also assayed. RESULTS:
      Large macrophage colony forming cells were detected in the peripheral blood of
      19% of patients with RA (18/96), but not in that of healthy controls. In
      addition, these cells were detected in the peripheral blood of 11 of the 38
      patients with other rheumatic disease (7/13 SSc and 4/11 PM/DM), but not in the
      23 patients with infectious diseases. In the patients with RA, interstitial lung
      disease was significantly more frequently observed among patients in whom colony
      forming cells were found than among those in whom they were not found (p <
      0.001). CONCLUSION: Based on the size of the colonies they formed, the macrophage
      colony forming cells detected in patients with RA probably corresponded to
      primitive hematopoietic progenitor cells, defined as high proliferative potential
      colony forming cells (HPP-CFC). Our observations provide preliminary evidence of
      the appearance of HPP-CFC in the circulation during inflammation of RA, and
      during that in other rheumatic diseases such as SSc and PM/DM, and of the
      association of HPP-CFC with interstitial lung disease in patients with RA.

PMID- 9263143
TI  - Concentrations and origins of soluble interleukin 6 receptor-alpha in serum and
      synovial fluid.
AB  - OBJECTIVE: To determine levels of soluble interleukin 6 receptor-alpha (sIL-6R
      alpha) in synovial fluid (SF) and serum from patients with different rheumatic
      diseases, and to analyze its cellular origin compared to IL-6. METHODS: IL-6 and
      sIL-6R alpha concentrations were measured in sera, SF, and culture supernatants
      of different cells types using specific sandwich ELISA. RESULTS: IL-6 levels were
      significantly higher (30 to 1000-fold) in SF than in sera, and higher in
      inflammatory arthropathies such as rheumatoid arthritis (RA), chondrocalcinosis,
      and gout than in osteoarthritis (OA). sIL-6R alpha levels in SF from patients
      with RA, gout, and chondrocalcinosis were also higher (24.7 +/- 7.5, 23.2 +/-
      9.1, and 19.5 +/- 7.4 ng/ml, respectively) than in patients with OA (10.1 +/- 5
      ng/ml), although the difference was distinctly smaller. In contrast, sIL-6R alpha
      concentrations did not differ significantly between the sera of healthy donors
      and patients. sIL-6R alpha levels were similar in SF and sera from inflammatory
      arthropathies, but lower in all osteoarthritic SF, compared to their
      corresponding serum. In contrast to IL-6, sIL-6R alpha was produced in high
      amounts by hepatocytes but not by structural cells of the joint (chondrocytes,
      synoviocytes, fibroblasts, and endothelial cells). Polymorphonuclear cells and
      mononuclear cells released intermediate levels. A significant correlation between
      sIL-6R alpha concentration and total number of leukocytes was observed in SF.
      CONCLUSION: Elevated levels of sIL-6R alpha were found in serum, likely to result
      from a marked release by hepatocytes in vitro. That levels are higher in
      inflammatory SF may be due in part to release by inflammatory cells in situ.

PMID- 9263145
TI  - Family history as a risk factor for rheumatoid arthritis: a case-control study.
AB  - OBJECTIVE: To investigate the risk of rheumatoid arthritis (RA) in the first
      degree relatives and to investigate whether the sex of the parent influences the
      pattern of inheritance. METHODS: An interview based case-control study, with
      subjects serially matched for age and sex. We analyzed 126 cases (hospital cases)
      and 94 controls (derived from the same hospitals), who gave information for
      family history of RA. Data concerning RA history among siblings and parents were
      computerized and analyzed univariately and multivariately. RESULTS: The odds
      ratio (OR) for developing RA is 4.4 (p < 0.001) if a first degree relative
      reported having the disease and 5.4 (p < 0.01) if a female first degree relative
      reported having the disease. For females the OR is 7.0 (p < 0.01) if the first
      degree relative is female. When the analysis was restricted to parents only, it
      was found that mothers with RA predispose their daughters and sons to develop RA
      more (OR = 8.6, p < 0.01, for daughters and 4.8, p < 0.05, for both sexes) than
      fathers (OR = 1.1 and 1.9, respectively). CONCLUSION: This case-control study
      confirms the familial clustering of RA and suggests that mothers confer
      susceptibility to RA on their offspring more often than fathers.

PMID- 9263146
TI  - Financial and career losses due to rheumatoid arthritis: a pilot study.
AB  - OBJECTIVE: To use a novel method of estimating income loss associated with
      rheumatoid arthritis (RA). METHODS: For the 26 RA patients (16 female and 10
      male, mean age 52.77 yrs) participating in our study, job histories were used to
      estimate earning potential based on the United States Department of Labor job
      analysis. To estimate current function, work samples were performed using the
      Valpar Instrument Battery. The tests include measures of motor coordination,
      finger dexterity, and manual dexterity. Databases were used to estimate current
      earning potential on the basis of these performance measures. RESULTS: Estimated
      earnings decreased from $18,409 to $13,900 per yr. Furthermore, it was estimated
      that the number of jobs patients could perform dropped from 11.5 million to 2.6
      million. CONCLUSION: These preliminary estimates suggest that RA causes
      significant reductions in earning potential and in the number of jobs that can be
      performed. This methodology, using a small sample of patients, produced results
      consistent with larger population studies.

PMID- 9263147
TI  - Efficacy of low load resistive muscle training in patients with rheumatoid
      arthritis functional class II and III.
AB  - OBJECTIVE: To determine the effect of a low load resistance exercise training
      program on muscle strength, functional outcome, and cardiovascular endurance.
      METHODS: Forty-nine patients, 37 women and 12 men between the ages of 35-76 yrs
      (mean 60.5 yrs), with definite rheumatoid arthritis (RA) functional class II and
      III (mean disease duration of 10.5 yrs) were randomly assigned to exercise and
      control groups for a 12 wk resistive muscle training program. A circuit weight
      bearing form of training was incorporated using light loads with high
      repetitions. A video tape demonstrating the exercises was given to all exercising
      participants to enable them to continue the program at home at least 3 times per
      wk with a biweekly self-report evaluation. Baseline and post-intervention
      evaluations included joint activity, muscle strength, endurance, functional
      outcome, and self-report. Cardiovascular fitness measured by treadmill time,
      anaerobic threshold and peak oxygen consumption (VO2) in this group were assessed
      at baseline and 12 wks. RESULTS: A significant improvement at 12 wks was noted in
      the exercise group for self-reported joint count (p = 0.02), number of painful
      joints (p = 0.004), HAQ (p = 0.012), sit-to-stand time (p = 0.02), grip strength
      (p = 0.05) knee extension 60 degrees (p = 0.03), Arthritis Impact Measurement
      Scales dexterity (p = 0.02), and time to anaerobic threshold (p = 0.03).
      Significant improvement in the exercise group compared to the control group was
      noted for self-reported joint count (p = 0.02), night time pain (p = 0.05), and
      sit-to-stand time (p = 0.02). Increase in treadmill time was not statistically
      significant nor was a change in peak oxygen consumption (VO2) noted.
      Abnormalities on initial treadmill screening were detected in 2 of 49
      asymptomatic patients. They were excluded from the study and subsequent workup
      revealed significant coronary artery disease. CONCLUSION: Low load resistive
      muscle training increased functional capacity as reported by patients and is a
      clinically safe form of exercise in functional class II and III RA. Screening
      this population for dormant coronary artery disease is recommended.

PMID- 9263148
TI  - Reduction in heart rate variability in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: To determine whether heart rate variability and cardiovascular reflex
      tests are abnormal in patients with systemic lupus erythematosus (SLE). METHODS:
      We measured heart rate variability (24 h ambulatory recordings), and used
      baroreflex sensitivity testing and cardiovascular reflex tests in a cross
      sectional, case-control study. Those taking drugs with cardiovascular activity
      were excluded. RESULTS: Determination of heart rate variability was simple to
      perform, well tolerated, and found to be reduced in the patients with lupus, but
      not strongly related to disease activity or duration. CONCLUSION: This may
      reflect underlying autonomic dysfunction; longitudinal studies will determine
      full clinical relevance.

PMID- 9263149
TI  - The antiphospholipid/cofactor syndromes. II. A variant in patients with systemic
      lupus erythematosus with antibodies to beta 2-glycoprotein I but no antibodies
      detectable in standard antiphospholipid assays.
AB  - OBJECTIVE: After the initial description of the anticardiolipin syndrome
      inpatients with systemic lupus erythematosus (SLE), it became clear that
      phospholipids other than cardiolipin could also be involved, that there could
      also be a primary syndrome, and that protein cofactors participate in in vitro
      reactivity of the autoantibodies. We describe 5 patients with SLE with clinical
      manifestations of antiphospholipid syndrome (APS) but persistently negative
      antiphospholipid antibodies (aPL). In all their tested sera we found antibodies
      to phospholipid-free beta 2-glycoprotein I (a beta 2-GPI). METHODS: We studied 5
      patients with SLE with at least 2 clinical manifestations of APS with no serum
      aPL detected in routine assays. IgG and IgM a beta 2-GPI were studied by ELISA
      and by Western blot. We also tested for antibodies to phosphatidylcholine,
      phosphatidylethanolamine, and phosphatidylserine by ELISA. We studied 54 normal
      sera as controls. RESULTS: Four patients had livedo reticularis, 2 had
      thrombocytopenia, 2 had hemolytic anemia, and one each had recurrent venous
      thromboses, repeated fetal loss, pulmonary arterial hypertension, and transverse
      myelitis. No patient had serum aPL, but all had high titers of IgG a beta 2-GPI
      (p < 0.001 vs controls). Reactivity found in ELISA was confirmed by Western blot.
      CONCLUSION: We describe a variant of APS in patients with SLE with negative aPL
      but serum antibodies to beta 2-GPI.

PMID- 9263150
TI  - Quantitative analysis of apoptosis and bcl-2 in Sjogren's syndrome.
AB  - OBJECTIVE: To determine whether apoptosis plays a significant role in tissue
      damage of Sjogren's syndrome (SS). METHODS: We performed a quantitative analysis
      of programmed cell death on salivary glands of 11 patients. Ten age matched women
      with sicca syndrome served as controls. Morphometric measurement of the
      fractional volume of acini and ducts showing DNA strand breaks was performed in
      sections stained by deoxynucleotidyl transferase assay. The extent of bcl-2
      expression was determined in sections labeled with monoclonal antibody. The
      different cell populations infiltrating the glands were examined in tissues
      stained with anti-leukocyte common antigen and OPD4 monoclonal antibodies.
      RESULTS: In patients with SS, 68% of the ductal epithelium was occupied by
      apoptotic structures, whereas only 12% of acini showed DNA strand breaks.
      Corresponding values in control salivary glands were 3 and 0.13%. bcl-2 labeling
      was higher in ducts than in acini of both control and pathologic glands. However,
      in SS a 43% (p < 0.001) and 75% (p < 0.001) reduction in bcl-2 expression was
      observed in ductal and acinar epithelium, respectively. In comparison with
      controls, the numerical density of CD4+ cells and plasma cells scattered
      throughout the interstitium was 323% and 203% higher (p < 0.001) in SS. Moreover,
      T helper/inducer lymphocytes represented 52% of the inflammatory foci.
      CONCLUSION: Apoptosis occurs in minor salivary glands of patients with SS with a
      prevailing localization on the ductal epithelium in association with
      downregulation of bcl-2 and a large number of infiltrating CD4+ lymphocytes.
      Thus, the destruction of glandular tissue and the loss of secretory function in
      SS is dependent on the activation of the suicide program of epithelial cells.

PMID- 9263151
TI  - Familial Mediterranean fever and hyperimmunoglobulinemia D syndrome: two diseases
      with distinct clinical, serologic, and genetic features.
AB  - OBJECTIVE: To determine whether the 2 periodic febrile syndromes familial
      Mediterranean fever (FMF) and hyperimmunoglobulinemia D syndrome (HIDS) are
      distinct diseases. METHODS: Clinical manifestations of the diseases were analyzed
      by physicians experienced with FMF and HIDS. Serum immunoglobulin (Ig) levels
      were studied in 70 patients with FMF using nephelometry or ELISA and compared
      with Ig levels in 50 patients with HIDS. Genetic linkage of HIDS with the
      chromosome 16 polymorphic locus RT70, currently used for refined localization of
      the FMF susceptibility gene (MEFV), was studied in 9 HIDS families (18 patients)
      using polymerase chain reaction amplification and gel electrophoresis. RESULTS:
      The main clinical features distinguishing FMF from HIDS were lymphadenectomy,
      skin eruption, and symmetrical oligoarthritis in HIDS, and monoarthritis,
      peritonitis, and pleuritis in FMF. Increased IgG levels were found in 12 patients
      with FMF (17%), IgA in 16 (23%), IgM in 9 (13%), and IgD in 9 (13%),
      significantly lower than the prevalence reported for HIDS. We found no evidence
      for genetic linkage between HIDS and the chromosome 16 marker RT70. CONCLUSION:
      HIDS and FMF are different entities, clinically, immunologically, and
      genetically.

PMID- 9263152
TI  - Amelioration of type II collagen induced arthritis in rats by treatment with
      thymulin.
AB  - OBJECTIVE: To investigate the effects of thymulin (serum thymic factor + Zn2+) in
      collagen induced arthritis (CIA) in rats. METHODS: SD rats were immunized with
      bovine type II collagen plus Freund's incomplete adjuvant, and thymulin was
      administered intraperitoneally on the first day of first immunization. We
      determined the level of serum thymulin by rosette inhibition assay. Effects of
      thymulin on CIA rats were estimated by measuring the extent of hind paw edema,
      the level of serum anti-type II collagen antibody, and changes in
      histopathological features of the affected joints. RESULTS: Serum thymulin levels
      in CIA rats were significantly lower than in untreated rats. Thymulin diminished
      hind paw swelling and onset of arthritis compared with control rats. The serum
      anti-type II collagen antibody level was also reduced by thymulin.
      Histopathological examination showed inhibition of granulation tissue and new
      bone formation after injection of thymulin. CONCLUSION: Our results suggest
      thymulin plays a significant role in the onset and development of CIA in rats.
      Our data indicate thymulin may be therapeutically effective in preventing the
      development of rheumatoid arthritis.

PMID- 9263153
TI  - Color Doppler sonography of the temporal arteries in giant cell arteritis and
      polymyalgia rheumatica.
AB  - OBJECTIVE: To test the diagnostic value of color Doppler sonography (CDS) of the
      superficial temporal arteries in patients suffering from giant cell arteritis
      (GCA). METHODS: The superficial temporal arteries and their frontal and parietal
      rami were examined by CDS in 11 patients with GCA, 21 patients with polymyalgia
      rheumatica (PMR), and 32 controls. The peak systolic velocity (Vmax) was measured
      at the tragus (proximal superficial temporal artery) and at the temporal bone
      (distal superficial temporal artery) level. Hypoechoic thickening of the vessel
      wall was systematically searched for. RESULTS: Mean Vmax in the proximal and
      distal superficial temporal artery was considerably lower in the GCA group [mean
      (+/- SEM) 30.9 (+/- 5.6) mm/s proximally and 5.8 (+/- 3.7) mm/s distally]
      compared to the PMR group [mean (+/- SEM) 64.6 (+/- 3.8) mm/s proximally and 49.3
      (+/- 4.2) mm/s distally] and the control group [mean (+/- SEM) 56.9 (+/- 2.2)
      mm/s proximally and 42.6 (+/- 2.2) distally]. Thickening of the vessel wall was
      found in only 2 patients: one with GCA and one with PMR. Followup of CDS in 6 GCA
      patients under treatment produced evidence of a significant increase in the mean
      Vmax at the distal site. CONCLUSION: Decreased blood flow velocity in the
      superficial temporal artery is very common in GCA patients and rare in PMR
      patients. Therefore, CDS examination may contribute to the diagnosis of GCA.

PMID- 9263154
TI  - Correlation between ossification of the stylohyoid ligament and osteophytes of
      the cervical spine.
AB  - OBJECTIVE: To investigate the correlation between ligamentous ossification or
      osteophytes of the cervical spine and ossification of the styloid process and
      stylohyoid ligament, and to determine any relation between diffuse idiopathic
      skeletal hyperostosis (DISH) of the thoracic spine and ossification of the
      styloid process and stylohyoid ligament. METHODS: Four patients having cervical
      spine DISH, an elongated styloid process and/or variable patterns of stylohyoid
      ligament ossification, and clinical findings compatible with Eagle's syndrome are
      described. Cervical computed tomography scans of 100 patients who also had
      lateral radiographs of the thoracic spine were reviewed. Point biserial and
      Spearman rank correlation analysis, McNemar test, chi-squared test, and Fisher's
      exact test were used to determine correlation between elongation of the styloid
      process and/or ossification of the stylohyoid ligament and (1) ligamentous
      ossification or osteophytes of the cervical spine (the characteristic spinal
      manifestation of DISH), and/or (2) DISH of the thoracic spine. RESULTS: (1)
      Elongation of the styloid process and variable patterns of ossification of the
      proximal, middle, and distal parts of the stylohyoid ligament, and (2)
      enlargement of this ligament were significantly correlated with transverse and
      anteroposterior dimensions of ligamentous ossification or osteophytes of the
      cervical spine at various levels. The prevalence of such abnormalities of this
      process and ligament was not significantly different between the patients with
      and without thoracic spine DISH. CONCLUSION: Variable types of styloid process
      stylohyoid ligament complex abnormalities have significant correlation with
      ligamentous ossification and osteophytes of the cervical spine.

PMID- 9263155
TI  - Cyclosporin A in the treatment of adult onset Still's disease.
AB  - OBJECTIVE: To determine whether cyclosporin A (CyA) is a useful option in the
      treatment of adult onset Still's disease (ASD). METHODS: Low dose CyA was given
      to 6 patients with chronic or relapsing ASD who had not been prescribed any other
      second line agents during the previous 6 mo. RESULTS: The disease completely
      remitted in 4 patients and improved markedly in the remaining 2. The
      corticosteroid requirement was substantially reduced in all cases. Tolerability
      was rated good or very good by all patients but one, who reported good tolerance
      to CyA only in a new formulation. CONCLUSION: CyA may be included among the
      second line agents used in the treatment of refractory ASD.

PMID- 9263156
TI  - Nucleotide pyrophosphohydrolase in human synovial fluid.
AB  - OBJECTIVE: To identify the molecular forms of ectonucleotide pyrophosphohydrolase
      (NTPPHase) in human synovial fluid (SF). METHODS: We examined synovial fluids
      from 32 patients with various joint diseases [10 calcium pyrophosphate dihydrate
      (CPPD) deposition disease; 7 osteoarthritis (OA); 6 rheumatoid arthritis (RA); 3
      after total knee arthroplasty (TKA); 6 olecranon bursa] and 3 normal joint
      fluids. Joint fluids were analyzed after sequential centrifugation for NTPPHase
      activity and by Western blot using polyclonal antibodies against 127 kDa porcine
      articular cartilage vesicle-associated NTPPHase and against PC-1 and 58 kDa, 2
      other ecto-NTPPHases. Lysate from human synoviocytes, porcine chondrocytes, and
      their conditioned media were examined using antibodies to these ecto-NTPPHases.
      Radiographs of joints from which fluid was obtained were graded for degenerative
      changes 0-4 using a standard method. RESULTS: NTPPHase activity was found in all
      pathological and normal SF tested and correlated with the degree of radiographic
      degeneration (r = 0.55, p < 0.05). NTPPHase specific activity in
      ultracentrifugation pellets was highest in CPPD deposition disease fluids (p <
      0.05). 127 kDa enzyme was found in both sedimentable and soluble fractions from
      CPPD, OA, TKA, and normal fluids, and was extensively degraded in all
      inflammatory fluids. Intact 115 kDa PC-1 was found only in the 2 CPPD fluids with
      the highest NTPPHase activity. 58 kDa enzyme was found in most fluids,
      predominantly in the soluble fraction. 127 kDa protein was identified in human
      synoviocyte conditioned media but not in cell lysate, while PC-1 and 58 kDa
      proteins were found in the cell lysate but not in the conditioned media.
      CONCLUSION: There was no disease specific association with any one ecto-NTPPHase.
      Total enzyme activity correlated with the degree of degenerative change. The
      specific activity of pelletable 127 kDa enzyme was higher in fluids containing
      CPPD crystals. All 3 ecto-NTPPHases or their presumed degradation products were
      detectable in some pathologic and normal fluids. A 200 kDa reactive band often
      accompanied reactivity to the 127 kDa enzyme. PC-1 and 127 kDa proteins were
      extensively degraded in inflammatory SF, while 58 kDa protein was not. The
      relative contribution of each of these enzymes to inorganic pyrophosphate
      production by human joint tissues remains unclear.

PMID- 9263157
TI  - An open, randomized study of ketoprofen in patients in surgery for Achilles or
      patellar tendinopathy.
AB  - OBJECTIVE: To assess the concentration of ketoprofen, after topical plaster
      application, in various tissues in relation to plasma levels in 60 patients
      undergoing surgery for Achilles or patellar tendinopathy; and to analyze whether
      tissues act as a reservoir of ketoprofen, by evaluating tissue concentrations in
      relation to plasma concentration at various time points after removal of the
      plaster. No attempt was made to study the clinical effect of treatment per se.
      METHODS: In random order to patients applied 30 mg plasters once daily for 5
      consecutive days (n = 30), or took a single oral dose 50 mg (n = 30) before
      surgery. Tissue samples of skin, subcutaneous fat, tendon sheath, and tendon, and
      plasma were collected intraoperatively at 0, 6 and 14 hours after removal of the
      5th plaster, and at 2, 6, and 14 hours after oral intake. Ketoprofen
      concentration was determined by a validated GC/MS method. The low limit of
      quantification was 0.5 ng/ml plasma and 0.5 ng/50 mg tissues. RESULTS: High
      concentrations of ketoprofen were observed in fat, tendon sheath, and tendon
      after topical applications, whereas plasma levels of ketoprofen were low.
      CONCLUSION: Ketoprofen attains high concentrations in subcutaneous tissues after
      multiple topical applications. Subcutaneous tissues appear to act as a reservoir
      of ketoprofen.

PMID- 9263158
TI  - Osteoarthritis of the hip and knee and mechanical occupational exposure--a
      systematic overview of the evidence.
AB  - OBJECTIVE: To clarify examine the epidemiologic evidence linking work related
      exposure to osteoarthritis (OA) of the hip and knee. METHODS: We investigated
      MEDLINE and EMBASE 1966-1994 with search terms of osteoarthritis, osteoarthrosis,
      arthrosis; risk factors, exposure; occupational diseases, agricultural workers'
      diseases, work. From 123 original studies on risk factors for OA, 17 studies were
      identified as providing a comparison group and relating the presence or absence
      of radiologically diagnosed OA to occupational factors. The quality of the
      methodology of each study was evaluated independently by 4 reviewers using a
      standardized protocol. RESULTS: Common methodological problems were encountered
      in areas such as representatives, recall of exposure, and evaluation of exposure
      and outcome. These problems often made a cause-effect relationship difficult to
      interpret. However, 7 of the 17 studies met our criteria for good methodological
      quality. A critical analysis of their results led to the following conclusions:
      (1) A consistently positive relationship exists between work involving knee
      bending and knee OA in men (range of odds ratio: 1.4-6). (2) The evidence
      suggesting a relationship between knee OA and occupational exposure in women is
      inconclusive. (3) A consistently positive but weak relationship exists between
      work related exposure (i.e., farming in particular) and hip OA in men. We felt we
      could not conclude with confidence that this relationship is strong due to the
      potential biases that exist in each of these studies. (4) No study attempted to
      investigate occupational exposure and hip OA in women. CONCLUSION: Studies
      suggest a strong positive relationship between work related knee bending exposure
      and knee OA. The evidence between work related exposure, farming in particular,
      and hip OA is consistently positive but weak.

PMID- 9263159
TI  - Consistency and validity of patient administered assessment of quality of life by
      the MOS SF-36; its association with disease activity and damage in patients with
      systemic lupus erythematosus.
AB  - OBJECTIVE: To investigate the metric properties and validity of the assessment of
      quality of life by the MOS Short Form 36 (SF-36) in patients with systemic lupus
      erythematosus (SLE) and to examine the effect of disease on quality of life.
      METHODS: Cross sectional study of 150 patients with SLE (age: mean 39.7 yrs, SD
      11.4 yrs; 95% female) attending 2 specialist lupus clinics between November 1994
      and April 1995. Shortly before or after the consultation patients completed the
      SF-36 and the MOS SF-20 with an additional question about fatigue (SF-20+) in
      random order. Disease activity was measured by the British Isles Lupus Activity
      Group System (BILAG), disease damage by the Systemic Lupus International
      Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index
      (SLICC). RESULTS: SF-36 domains were shown to be internally consistent
      (Cronbach's coefficient alpha > or = 0.71). Significant associations of the SF-36
      domains with the corresponding domains of the SF-20+ and with global disease
      activity measured by BILAG were observed. SF-36 scores in patients with SLE were
      significantly lower than in controls. Different disease activity levels were
      significantly associated with different quality of life scores, with excellent
      ability to record the continuum from good health to serious illness by the SF-36.
      Disease activity had greater effect on quality of life than age, cumulative
      damage, or disease duration. CONCLUSION: This study shows the SF-36 is internally
      consistent and proves construct, discriminatory, and criterion validity for the
      SF-36 and construct validity for the SF-20+ in patients with SLE. The SF-36 is
      preferred because of its broader scope of questions, its widespread use, and
      previous international validation for a wide variety of diseases.

PMID- 9263161
TI  - Strategies for assessing pain and pain exaggeration: controlled studies.
AB  - OBJECTIVE: To compare structured with intuitive methods of detecting exaggerated
      pain, in 2 randomized studies, with masked observers, and to compare properties
      of measures of relative tenderness, as surrogates for measures of pain. METHODS:
      Pairs of experienced rheumatologists assessed tenderness and behavior in subjects
      who were either giving honest responses (Not Acting) or exaggerating their
      tenderness while hiding the deception (Acting). In Study 1 (20 subjects) the
      assessments of behavior were descriptive only; for Study 2 (25 subjects) a
      prestructured format was developed. The challenge to the examiners was to detect
      Acting. The challenge to the analyst was to develop, from the recorded data, an
      algorithm that described or bettered the examiners' performance. RESULTS: By
      exaggerating, nontender patients could meet formal ACR criteria for fibromyalgia.
      The addition of a prestructured pain behavior assessment in Study 2 was
      associated with improvement in the observers' ability to detect Acting, with
      improvement of sensitivity from 60 to 90% (p = 0.0003, Study 2 compared with
      Study 1). False positive diagnoses of Acting by the observers were uniformly
      uncommon, with specificity of 85 and 86% in the 2 studies. CONCLUSION: Formal
      numerical techniques are required and feasible for separately assessing the
      structural and psychogenic components of chronic pain.

PMID- 9263160
TI  - Fibromyalgia--are there different mechanisms in the processing of pain? A double
      blind crossover comparison of analgesic drugs.
AB  - OBJECTIVE: Pain was analyzed in patients with fibromyalgia (FM) in a randomized,
      double blind, crossover study using intravenous (i.v.) administration of
      different drugs. METHODS: In 18 patients with FM muscle pain to i.v.
      administration of morphine (0.3 mg/kg), lidocaine (5 mg/kg), ketamine (0.3
      mg/kg), or saline was studied. Spontaneous pain intensity, muscle strength,
      static muscle endurance, pressure pain threshold, and pain tolerance at tender
      points and non-tender point areas were followed. Drug plasma concentrations and
      effects on physical functioning ability score (FIQ) were recorded. A personality
      inventory (KSP) was used to related pain response to personality traits. RESULTS:
      Thirteen patients responded to one or several of the drugs, but not to placebo.
      Two patients were placebo responders responding to all 4 infusions. Three were
      nonresponders responding to no infusions. Seven of the responders had a reduction
      in pain for 1-5 days. Pressure pain threshold and pain tolerance increased
      significantly in responders. Plasma concentrations were similar in responders and
      nonresponders. FIQ values improved significantly after the ketamine infusion.
      Responders scored higher on KSP scales for somatic anxiety, muscular tension, and
      psychasthenia compared with healthy controls. CONCLUSION: FM diagnosed according
      to the American College of Rheumatology criteria seems to include patients with
      different pain processing mechanisms. A pharmacological pain analysis with
      subdivision into responders and nonresponders might be considered before
      instituting therapeutic interventions or research.

PMID- 9263162
TI  - WHO/ILAR Taskforce on quality of life.

PMID- 9263163
TI  - Total assessment of rheumatoid polyarthritis--a postgraduate training program for
      physical and occupational therapists: a 20 year success story.

PMID- 9263164
TI  - Fatal exacerbation of systemic lupus erythematosus after induction of ovulation.
AB  - It is well known that sex hormones can regulate the course of systemic lupus
      erythematosus (SLE). We describe a young woman who had a fatal exacerbation of
      SLE after controlled ovarian hyperstimulation for induction of ovulation. We
      recommend careful attention to the immunological status of the infertile women
      before starting any ovulation inducing treatment for assisted reproduction.

PMID- 9263165
TI  - Relapse of polymyositis after prolonged remission.
AB  - We describe the case of a patient with polymyositis and anti-Jo-1 antibodies who
      experienced a relapse of his inflammatory muscle disease after 7 years of
      clinical remission. Our review of the literature shows that remission is achieved
      in 25-68% of patients treated with high dose corticosteroids as part of their
      initial therapy. Relapse rates after complete remission vary from 6 to 43% in the
      few studies where this information is available. Late relapses after initial
      remission appear to be unusual, but may be more frequent in patients like this
      one with antisynthetase syndrome.

PMID- 9263166
TI  - Adult onset Still's disease associated hemophagocytosis.
AB  - Reactive hemophagocytosis is characterized by the activation of histiocytes with
      prominent hemophagocytosis in the reticuloendothelial system, and usually occurs
      in association with underlying disorders such as viral or bacterial infection and
      malignancy. We describe 3 cases of adult onset Still's disease (AOSD) who
      developed hemophagocytosis in bone marrow. Extensive studies could not identify
      any viral infection or other known underlying disorders for reactive
      hemophagocytosis except for active AOSD. Although the causative mechanisms of
      reactive hemophagocytosis in AOSD are not clear, our cases suggest the
      possibility of AOSD associated hemophagocytosis.

PMID- 9263167
TI  - Pasteurella multocida infectious arthritis with acute gout after a cat bite.
AB  - A 74-year-old man with chronic lymphocytic leukemia, immune purpura, and gout
      presented with a painful, swollen ankle after a cat bite to his leg. On
      aspiration of the ankle, gram negative pleomorphic rods and monosodium urate
      crystals were seen and Pasteurella multocida was cultured. He was treated with
      ampicillin/sulbactam, joint aspiration, and intraarticular steroids, with
      resolution of infection and return of joint function. The syndromes of
      Pasteurella arthritis and crystal arthropathy with septic arthritis are reviewed.

PMID- 9263168
TI  - The continuing challenge of predictive factors in rheumatoid arthritis.

PMID- 9263169
TI  - Childhood sarcoidosis--does age of onset predict clinical manifestations?

PMID- 9263170
TI  - Axonal neuropathy in a patient receiving interferon-alpha therapy for chronic
      hepatitis C.

PMID- 9263171
TI  - Musculoskeletal complaints and fibromyalgia in patients attending a respiratory
      sleep disorders clinic.

PMID- 9263172
TI  - On the antiphospholipid/cofactor syndromes.

PMID- 9263173
TI  - Temporal arteritis in Israel.

PMID- 9263174
TI  - IL-10 plasma levels correlate with disease activity in spondyloarthropathy.

PMID- 9263175
TI  - Unusual pulmonary manifestations of Takayasu's arteritis.

PMID- 9263176
TI  - Sjogren's syndrome associated with hypokalemic myopathy due to Bartter's
      syndrome.

PMID- 9263177
TI  - Diet and gene interaction.

PMID- 9263178
TI  - Diet, genetics and hypertension.
AB  - It is generally accepted that genetics play a significant role in the
      pathogenesis of hypertension. Since hypertension often follows kidney
      transplantation, candidate genes have been sought and found in the kidneys of
      rats and humans. One well-recognized, inherited influence on blood pressure (BP)
      occurs via abnormal renal sodium handling in vivo. Further, abnormal renal sodium
      handling is seen in isolated kidneys of genetically hypertensive rats. People who
      have a relative inability to handle a sodium load properly, and retain it
      inappropriately, often develop high BP and are referred to as "salt-sensitive".
      More than half of patients diagnosed with essential hypertension are salt
      sensitive. In contrast to the deleterious effects associated with high sodium
      intake, many believe that ingestion of more potassium, calcium, and magnesium may
      influence BP favorably. The beneficial effects of these ions work, at least in
      part, through an effect on sodium balance, i.e. a diuretic influence. In support
      of this concept, they lower BP more effectively in salt-sensitive hypertensives.
      Refined carbohydrates and saturated fats are also associated with salt retention
      and hypertension. Thus, dietary factors, working directly on their own and/or
      indirectly via effects on genetic mechanisms, may alter BP favorably or
      unfavorably.

PMID- 9263179
TI  - Genetic factors influence the atherogenic response of lipoproteins to dietary fat
      and cholesterol in nonhuman primates.
AB  - Comparative studies of diet responsiveness have carried out in five different old
      world primate species, including African green, stumptail, rhesus, patas, and
      cynomolgus monkeys. The dietary variables examined were level of cholesterol
      (0.03 and 0.8 mg cholesterol/kcal) and type of fat (enriched in saturated vs. n-6
      polyunsaturated fatty acids). In all cases, hypercholesterolemia resulted from
      the high cholesterol diet, making it possible to identify low, moderate, and high
      responding species. Polyunsaturated vs. saturated fat effects to lower plasma
      cholesterol did not appear to be remarkably species specific, except for the more
      pronounced response in African green monkeys. For low-density lipoprotein (LDL)
      cholesterol concentrations, African green monkeys were the lowest responding
      species and cynomolgus monkeys were the highest. LDL particle enlargement was
      least in African green monkeys and highest in rhesus and cynomolgus monkeys. High
      density lipoprotein (HDL) cholesterol levels were similar among species on the
      low cholesterol diet, but decreased when the high cholesterol diet was fed in all
      species except African green monkeys, where HDL increased with added dietary
      cholesterol. Coronary artery atherosclerosis developed only when the high
      cholesterol diet was fed, occurred more rapidly, and became more extensive in
      cynomolgus compared to African green monkeys. Polyunsaturated fat limited the
      amount of atherosclerosis that developed in both species. Genetic factors
      regulating the response to dietary cholesterol in degree of hyperlipoproteinemia,
      cholesterol distribution among lipoproteins, LDL particle size, and HDL
      cholesterol concentration were characteristically unique among different primate
      species. The effects of lipoproteins were well correlated with the extent of
      coronary artery atherosclerosis.

PMID- 9263180
TI  - Diet-gene interactions in human lipoprotein metabolism.
AB  - Genetic variation can influence the effects of hypocholesterolemic dietary
      interventions on lipoproteins involved in coronary artery disease (CAD).
      Individuals with the E4 allelic variant of the apo E gene exhibit greater low
      density lipoprotein (LDL) cholesterol reductions on low-fat, low-cholesterol
      diets than subjects with other alleles. Another apolipoprotein structural
      variant, apo A-IV-2, attenuates the response of LDL cholesterol to dietary
      cholesterol. Other studies have associated lipoprotein response to dietary
      modifications with DNA polymorphisms in the genes for apo B and the LDL receptor,
      and in the promoter region of the apo A-I gene. Studies in our laboratory
      involving variation in dietary fat and carbohydrate intake have demonstrated that
      alleles at the apo E gene locus are associated with changes in large, buoyant but
      not smaller, denser LDL subclasses. On the other hand, a low-fat diet induces a
      reduction in small, dense LDL in individuals with a genetically influenced
      metabolic profile characterized by a predominance of these particles. Moreover,
      reductions in LDL cholesterol and apo B in these subjects are greater than in the
      majority of subjects with larger LDL. Since in humans a predominance of small LDL
      signifies a higher risk for coronary artery disease than that associated with
      larger LDL, metabolic and genetic factors contributing to the small LDL trait may
      account for a substantial portion of the coronary risk benefit attributed to
      reduced-fat diets. Studies in large population groups or in suitable animal
      models will be necessary to determine the impact of genetic influences on dietary
      response affecting lipoprotein metabolism and their interactions with other
      environmental and hormonal factors.

PMID- 9263181
TI  - Genetic effects on bone mass and turnover-relevance to black/white differences.
AB  - The mass of a bone is given by its volume and its apparent density--mass per unit
      external volume. Most measurements of so-called density are of mass incompletely
      normalized by some index of bone size. Genes control about 60% to 75% of the
      variance of peak bone mass/density and a much smaller proportion of the variance
      in rate of loss. Genetic influence on bone mass/density are mediated in large
      part by body size, bone size, and muscle mass. Most of the fifty-fold increase in
      bone mass from birth to maturity is due to bone growth, which is linked to muscle
      growth and bodily growth. Three-D apparent bone density in the vertebrae
      increases about 15% during the pubertal growth spurt. The genetic potential for
      bone accumulation can be frustrated by insufficient calcium intake, disruption of
      the calendar of puberty and inadequate physical activity. The growing skeleton is
      much more responsive than the mature skeleton to the osteotrophic effect of
      exercise, which is mediated by the detection of deviations from a target value
      for strain, and orchestration of cellular responses that restore the target
      value, processes collectively termed the mechanostat. Production of metaphyseal
      cancellous bone and growth in length are both linked to endochondral
      ossification, which is driven by growth plate cartilage cell proliferation.
      Production of diaphyseal cortical bone and growth in width are both linked to
      periosteal apposition, which is driven by osteoblast precursor proliferation.
      During adolescence trabeculae and cortices become thicker by net endosteal
      apposition, which increases apparent density. Two lines of evidence support a
      genetic basis for black/white differences in bone mass. First, the magnitude (10%
      to 40%) is incommensurate with known nongenetic factors. Second, the difference
      is already evident in the fetus and increases progressively during growth,
      especially in adolescence; the difference in peak bone mass persists throughout
      life. The genetic determination of bone mass is mediated by two classes of gene.
      The first regulates growth of the body, including muscles and bones, under the
      control of a master gene or set of genes whose products function as the sizostat.
      The second regulates the increase in apparent bone density in response to load
      bearing, under the control of a master gene or set of genes whose products
      function as the mechanostat.

PMID- 9263182
TI  - Infants diets and insulin-dependent diabetes: evaluating the "cows' milk
      hypothesis" and a role for anti-bovine serum albumin immunity.
AB  - Insulin-Dependent Diabetes (IDD) results from an autoimmune destruction of the
      insulin secreting pancreatic beta cells. The immunological mechanisms underlying
      the development of IDD as well as the role of environmental agents (e.g., diet,
      viruses, stress) in the pathogenesis of the disease are the subject of
      considerable research efforts. Significant attention has recently been directed
      to a hypothesis that consumption of cows' milk in infancy may trigger the
      autoimmune process underlying IDD. Early evidence supporting this "cows' milk
      hypothesis" included case-control studies surveying infant nutrition practices
      (i.e., breast feeding versus consumption of infant formula) and the subsequent
      development of IDD. However, intense media interest surrounding a report
      indicating anti-bovine serum albumin (BSA) immunity as the cause of IDD has lead
      to heightened public awareness of the issue, and, together with the
      epidemiological data, prompted The American Academy of Pediatrics to modify its
      guidelines for infant feeding practices. However, less public and scientific
      attention has been given toward the observations that many of these case-control
      studies were retrospective in design and subject to recall bias, narrow in scope
      in terms of collecting dietary information, and that similar results have not
      been duplicated in other more recent (and better designed) investigations.
      Furthermore, the immunological report implicating anti-BSA immunity with the
      disease has become controversial due to difficulties in conforming the findings,
      and experiments in animal models closely resembling human IDD have not uniformly
      supported a role for anti-BSA immunity in the pathogenesis of IDD. Given the
      significant morbidity and mortality associated with IDD, an improved
      understanding of the cause of this disorder as well as identifying possible
      methods for its prevention are essential. However, without additional supporting
      information, modification of the cows' milk/BSA composition of diets in order to
      avoid the disease may be premature. Further studies are needed to clearly
      establish a role for diet in the pathogenesis of IDD.

PMID- 9263183
TI  - Comparison of the enzyme activities between the thickest and the thinnest parts
      of the abdominal pannus.
AB  - OBJECTIVE: According to some reports, there are variations in metabolism in
      adipocytes from different areas of the body. The purpose of this study was to
      determine if there are differences in some of the lipid assimilating enzyme
      activities between the thickest (overhang) and the thinnest (upper margin) parts
      of the abdominal pannus. METHODS: The abdominal panniculectomy activities of sn
      glycerol-3-phosphate dehydrogenase (31 subjects, spectrophotometric method),
      fatty acid synthetase (14 subjects, spectrophotometric method) and lipoprotein
      lipase (18 subjects, radioactive method) were determined in the thickest and the
      thinnest parts of the pannus of lipectomy patients. RESULTS: The enzyme
      activities were as follows: sn-glycerol-3-phosphate dehydrogenase: thickest: 2083
      +/- 227.7 nm/mg/min; thinnest: 2084 +/- 208.3 nm/mg/min (p < 0.098, T = 0.02).
      Fatty acid synthetase: thickest: 22.0 +/- 3.9 microns/mg/min; thinnest 25.9 +/-
      6.9 microns/mg/min (p < 0.36, T = 0.94). Lipoprotein lipase: thickest: 0.70 +/-
      0.11% of control; thinnest: 0.61 +/- 0.14% of control (p < 0.47, T = 0.75). Thus
      no differences in specific enzyme activities were found between the two sites
      studied. CONCLUSIONS: There was no difference in the activity of the enzymes
      studied at the thickest and the thinnest part of the pannus.

PMID- 9263184
TI  - Impaired endocrine and exocrine pancreatic functions in copper-deficient rats:
      the effect of gender.
AB  - OBJECTIVE: To examine the effect of gender on endocrine and exocrine pancreatic
      function in female and male rats fed from weaning a copper-deficient diet.
      METHODS: Weanling male and female rats were fed a copper-deficient or adequate
      diet for 4 weeks. Rats were sacrificed after an overnight fast. Livers and
      pancreata were removed, weighed and the concentrations of copper and iron were
      determined. In addition, insulin was measured in pancreatic tissue and plasma.
      Lipase and amylase activities were measured in pancreas. Lipid peroxidation was
      assessed in liver. RESULTS: Copper deficiency in the male resulted in a profound
      reduced glandular mass of the pancreas. The pancreas continued low activities of
      lipase and amylase but excessive levels of insulin. Iron retention in the
      pancreas of the copper-deficient male rat was greater than in the female
      counterpart. Effects of copper deficiency in female rats on pancreas mass and
      endocrine pancreas were of lesser magnitude compared with males. Plasma insulin
      in the female rat was much higher than in the male rat. Hepatic lipid
      peroxidation was increased by copper deficiency in the male rat but was
      unaffected in the female. CONCLUSIONS: Data show that pancreatic atrophy is more
      pronounced in males compared with females, and the endocrine pancreas of the male
      is more susceptible to dietary copper deprivation than the female rat. The
      greater degree of pancreatic atrophy and associated abnormalities in males
      compared with females may be related to the greater retention of pancreatic iron
      and subsequent peroxidative damage.

PMID- 9263185
TI  - Effect of magnesium deficiency on vitamin B2 and B6 status in the rat.
AB  - OBJECTIVE: The present study was undertaken to investigate the effect of dietary
      magnesium (Mg) deficiency on vitamin B2 (riboflavin) and B6 (pyridoxine) status
      in rats. METHODS: We fed Wistar rats an Mg-deficient diet (56 mg magnesium per kg
      food) for 70 days. On days 21, 35 and 70 we measured Mg and manganese (Mn) in
      plasma and whole blood, alkaline phosphatase in plasma, erythrocyte glutathione
      reductase activity coefficient (AC-EGR) for riboflavin status, and erythrocyte
      aspartase transaminase activity coefficient (AC-EAST) for vitamin B6 status.
      RESULTS: Intake of the Mg-deficient diet significantly decreased plasma and whole
      blood levels of Mg and plasma alkaline phosphatase activity on all sampling days.
      The Mg deficit had no effect on plasma concentrations of Mn, but significantly
      increased whole blood levels of this element on days 35 and 70. The Mg-deficient
      diet had no effect on AC-EGR, and thus appeared not to affect riboflavin status.
      However, AC-EAST was significantly increased on day 70, implying that the animals
      were at risk for vitamin B6 deficiency. CONCLUSION: Mg deficiency impairs vitamin
      B6 status by depleting intracellular Mg and thus inhibits the activity of
      alkaline phosphatase, a metalloenzyme required for the uptake of pyridoxal
      phosphate by tissues. Although part of the intraerythrocyte loss of Mg is
      countervailed by Mn, which can act as a substitute activator of alkaline
      phosphatase, the degree of compensation is insufficient to fully offset the
      decrease in activity caused by Mg depletion.

PMID- 9263187
TI  - Nutritional disorders in a concentration camp.
AB  - OBJECTIVE: Observations on nutritional disorders were made by a physician inmate
      in a concentration camp before and during the Great Starvation in China.
      METHODS/RESULTS: Based on therapeutic response, many unique abnormalities should
      be considered as a part of clinical picture of malnutrition, such as
      mucocutaneous pigmentation, nail layering phenomena and intranail hemorrhage,
      palmar/plantar fissures, vegetative system crisis, a avitaminostic fevers,
      multiple premature beats, and enlargement of cartilage, lymph nodes, and
      submandibular glands. DISCUSSION: Thiamin deficiency should be also considered as
      one, if not the only, etiologic factor of several common disorders, including
      submandibular gland cyst, Baker's cyst, stenosing tenosynovitis, direct inguinal
      hernia, among others.

PMID- 9263186
TI  - Effect of a two-year supplementation with low doses of antioxidant vitamins
      and/or minerals in elderly subjects on levels of nutrients and antioxidant
      defense parameters.
AB  - BACKGROUND: Eighty-one elderly hospitalized subjects (> 65 years) were recruited
      for a double-blind placebo-controlled study to examine low dose supplementation
      of antioxidant vitamins and minerals on biological and functional parameters of
      free radical metabolism. Subjects were randomly assigned to one of the four
      treatment groups, daily receiving for 2 years: placebo group; mineral group: 20
      mg zinc, 100 micrograms selenium; vitamin group: 120 mg vitamin C (Vit C), 6 mg
      beta-carotene (beta CA), 15 mg vitamin E (Vit E); mineral and vitamin group: Zn
      20 mg, Se 100 micrograms, Vit C 120 mg, beta CA 6 mg, Vit E 15 mg. RESULTS: Fifty
      seven subjects completed the study. A large frequency of Vit C, Zn and Se
      deficiencies were observed at baseline. As early as 6 months of treatment, a
      significant increase in vitamin and mineral serum levels was observed in the
      corresponding groups. The increases ranged from 1.1-4.0 fold depending on the
      nutrient. Antioxidant defense, studied in vitro with a test using red blood cells
      in presence of 2,2'-azo-bis (2-amidinopropane) by hydrochloride, showed an
      increase of cell resistance in patients receiving vitamins (p = 0.002); it was
      positively correlated with serum Vit C (p < 0.0001), alpha-tocopherol/cholesterol
      (p = 0.06), beta CA (p = 0.0014), serum Cu and Se (p < 0.05). Moreover, red blood
      cell antioxidant defense was reduced in elderly compared with young control
      subjects (50% hemolysis time: 69 +/- 14 mn and 109 +/- 12 mn, respectively).
      Erythrocyte glutathione peroxidase activity was enhanced in groups receiving
      minerals, whereas no significant change was observed for other indicators of
      oxidative stress (erythrocyte superoxide dismutase activity, thiobarbituric acid
      reactive substances, total glutathione, reduced and oxidized forms). DISCUSSION:
      Our results provide experimental evidence that a low dose supplementation with
      vitamins and minerals was able to normalize biological nutrient status as early
      as 6 months of treatment. In addition, our data indicate that antioxidant defense
      in elderly subjects was improved with low doses of vit C, vit E and beta CA as
      studied by means of a functional test utilizing red blood cells challenged in
      vitro with free radicals.

PMID- 9263188
TI  - Effect of technological treatments on digestibility and allergenicity of meat
      based baby foods.
AB  - OBJECTIVE: When suitability prepared according to particular characteristics of
      hygiene and digestibility, meat is an important food for human weaning. The
      present knowledge on meat digestibility and allergenicity are not enough to
      justify removal of meat from a child's diet when there is risk but no clinical
      evidence of allergy. Based on these considerations, the role of technological
      treatments on digestibility and allergenicity of meat-based baby foods is
      considered. SUBJECTS: Eight children (five males and three females) suffering
      from atopic dermatitis (AD), aged 3.8 to 7.1 years (mean age 4.86 +/- 1.10
      years). STUDY DESIGN AND METHODS: An in vitro multienzymatic digestibility assay
      was used to evaluate proteolysis in meat samples (from four different animal
      species). The experimental design included raw, steam-cooked (home-made and
      industrial cooking), homogenized (strained) and freeze-dried meat samples. Skin
      prick test (SPT) was performed to evaluate positive responses to meat samples
      (raw, cooked, strained and freeze-dried) from four animal species. RESULTS: Our
      data indicate that enzymatic attack is strongly affected by heat treatment as
      shown in steam-cooked meat samples. On the other hand, blending, homogenization
      and freeze-drying processes are able to partially reverse the phenomenon. Data on
      modification of sodium dodecyl sulfate-polyacrylamide gel rlectrophoresis (SDS
      PAGE) protein pattern during the multienzymatic assay are reported. Cooking and
      technological treatments reduce positive responses obtained in SPT. CONCLUSIONS:
      Technological treatments improve digestibility and reduce antigenicity of meat
      products.

PMID- 9263190
TI  - Modeling the relation between neurofibrillary tangles and intellectual status.
AB  - The relationship between the neurofibrillary tangles and the intellectual deficit
      observed in senile dementia of the Alzheimer type was studied in 27 patients over
      the age of 75. The presence and density of tau positive tangles were assessed in
      six areas including limbic, paralimbic, and isocortical cortices. In the
      isocortical areas, the presence [1] or absence [0] of neurofibrillary tangles was
      better correlated with the Blessed test score than the density of the
      neurofibrillary tangles profiles. Multivariate analysis showed that the number of
      areas containing at least one neurofibrillary tangle was the best explanatory
      variable of the intellectual status. The cortical areas were ranked according to
      the prevalence of their involvement. The presence of tangles in an area of a
      given rank took place only if the areas of lower ranks were also involved. It is
      proposed that the presence of tangles in a given area is a more significant
      information than the value of their density. These data may lead to new
      diagnostic procedures.

PMID- 9263189
TI  - Meat allergy: III--Proteins involved and cross-reactivity between different
      animal species.
AB  - BACKGROUND: Although relatively infrequent, meat allergy represents a serious
      problem for children both because it is generally associated with intolerance to
      other protein sources and because of the suggested role of meat in stimulating
      the gastrointestinal development during weaning. OBJECTIVE: With these
      considerations, the aim of our work was to improve biological-biochemical
      knowledge of meat allergy. METHODS: This study was performed using in vivo skin
      prick test (SPT) and in vitro (electrophoresis associated with the immunoblotting
      technique) tests. RESULTS: Bovine serum albumin (BSA) and actin were the proteins
      most frequently involved in binding with the circulating IgE. BSA involvement was
      confirmed by SPT; the high number of positive responses observed with actin in
      immunoblotting was not confirmed by SPT data. Cross-reactivity between serum
      albumins from different animal species was demonstrated. Our studies show that in
      this group of children, the correspondence between the percentage of sequence
      identity (phylogenetic similarity) and the number of positive responses was
      surprisingly high. CONCLUSIONS: Although further studies are necessary, the data
      reported here provide new biochemical data on meat allergy.

PMID- 9263191
TI  - Decrease in adenylate cyclase activity antecedes neurofibrillary tangle
      formation.
AB  - In previous studies, the formation of cAMP was seen to be significantly reduced
      in various brain regions in Alzheimer patients. Recently, a staging system was
      introduced in which Alzheimer-related. histopathological changes were classified
      according to the pattern of alterations rather than their density. In this study,
      we examined the degree of correlation between these stages and the postmortem
      activity of the CAMP-generating enzyme adenylate cyclase. Our findings suggest
      that forskolin-stimulated adenylate cyclase activity is significantly decreased
      before major neurofibrillary changes develop. Early impairment of postreceptor
      signalling could have potentially important consequences for drug treatment
      and/or for the development of neurofibrillary changes.

PMID- 9263192
TI  - Free intracellular calcium in peripheral cells in Alzheimer's disease.
AB  - The goal of the present study was to evaluate several parameters of free
      intracellular Ca2+ regulation ([Ca2+]i) in Alzheimer's disease (AD) in a very
      large group of patients (n = 50) and nondemented controls (n = 41), using blood
      lymphocytes and neutrophils as two different peripheral model systems. We found
      no major difference, because neither the basal [Ca2+]i, nor the activation
      induced Ca2+ responses differed among neutrophils or lymphocytes from aged
      controls and AD patients. However, we observed a delayed Ca2+ response of AD
      lymphocytes after phytohemagglutinin (PHA) stimulation, indicating an impaired
      function of Ca2+ influx-controlling mechanisms, because Ca2+ release from
      intracellular stores appears to be unchanged. Because the PHA-induced Ca2+
      response in lymphocytes is accelerated by beta-amyloid (Beta A) similarly to its
      effects on central neurons, we also investigated the effect of beta A on Ca2+
      signalling with regard to AD-related alterations. In contrast to lymphocytes from
      aged controls, the amplifying effect on Ca2+ signalling was significantly reduced
      in lymphocytes from a high percentage of AD patients. The results are discussed
      with respect to their diagnostic potential and to a possible involvement of
      altered beta A sensitivity of lymphocytes in the pathophysiology of AD.

PMID- 9263193
TI  - Twenty-four hour cortisol release profiles in patients with Alzheimer's and
      Parkinson's disease compared to normal controls: ultradian secretory pulsatility
      and diurnal variation.
AB  - Endocrine abnormalities of the hypothalamic-pituitary-adrenal (HPA) system in
      patients with Alzheimer's disease (AD) and Parkinson's disease (PD) have been
      described repeatedly. However, no data are available on the diurnal cortisol
      secretory pattern in these major neurodegenerative disorders. Therefore, we
      studied 24-h pulsatile cortisol secretion in 12 patients with AD and 12 patients
      with PD compared to 10 normal community- and age-matched volunteers (NV). Twenty
      four hour blood sampling was performed from 1800 h to 1800 h at 15-min intervals.
      Cortisol half-life, number of cortisol secretory bursts/24-h, interpulse
      interval, mass of cortisol secreted per burst, amplitude of cortisol secretory
      bursts, pulsatile cortisol production rate, 24-h mean, and integral cortisol
      concentrations were calculated by applying deconvolution analysis. Furthermore,
      the relative diurnal variation and the quiescent period were determined. Patients
      with AD and PD were found to have significantly higher total plasma cortisol
      concentrations (24-h pulsatile cortisol production rate: AD + 56%; PD + 52%/24-h
      integrated cortisol: AD + 37%; PD + 29%) compared to NV. This sustained
      hypercortisolism is due to a higher mass of cortisol secreted per burst (AD +
      62%; PD + 79%), but not to increased cortisol half-life or secretory pulse
      frequency or amplitude. Despite these similarities between AD and PD patients,
      relative diurnal variation of cortisol secretion was significantly decreased in
      patients with PD (-22%), whereas the pattern of secretory curves was not
      different between NV and AD patients. This observation was indirectly supported
      by a reduction of the quiescent period in patients with PD (-74 min) compared to
      the NV and AD group. Based on these results and recently published animal data,
      we hypothesize that decreased expression of hippocampal mineralocorticoid
      receptors (MR) may account for the flattened diurnal cortisol secretory curve
      observed in PD patients, whereas the intact diurnal profile in AD patients may be
      due to a relative increase in MR compensating for the hippocampal neuronal loss
      commonly occurring in this disorder.

PMID- 9263194
TI  - Erythrocyte aging characteristics in elderly individuals with beginning dementia.
AB  - An increase in erythrocyte-bound IgG and enhanced breakdown of the erythrocyte
      anion exchanger band 3, characteristics of normal erythrocyte aging are observed
      in old, healthy individuals when compared with young donors. These findings
      indicate that the rate of cellular aging increases with organismal aging. Results
      from previous studies on the same parameters have suggested that the erythrocyte
      aging process is disturbed in patients in advanced stages of Alzheimer type
      dementia, and in individuals with Down's syndrome who show no signs of dementia.
      In this study we find no changes in erythrocyte aging parameters in old
      individuals in beginning stages of dementia of various etiologies. We conclude
      that, in general, characteristics of disturbed erythrocyte aging cannot serve as
      presymptomatic markers of Alzheimer-type dementia.

PMID- 9263195
TI  - Effect of glucose and peripheral glucose regulation on memory in the elderly.
AB  - We examined changes in cognitive performance following the intake of a glucose
      (50 g) or saccharin solution (50 mg) in fasted elderly male and female subjects.
      Glucoregulation was estimated using a recovery index that was used to categorize
      subjects within each sex as having poor or good recovery. Elderly males with poor
      recovery performed worse on the Logical Memory subtest of the Wechsler Memory
      Scale and on the free recall or recognition parts of a work list task. The item
      analysis of the Logical Memory subtest showed that male subjects with poor
      recovery remembered less of the last items of the paragraphs after drinking
      saccharin while the first items were equally remembered by both groups. Glucose
      improved the performance of the males with good regulation for the first seven
      items while the performance of males with poor regulation decreased for those
      items under glucose. The present study support the notion that peripheral
      glucoregulation can influence memory performance and that the ingestion of
      glucose can influence certain aspects of memory functioning.

PMID- 9263196
TI  - Elevated phosphocholine and phosphatidylcholine following rat entorhinal cortex
      lesions.
AB  - At early stages of Alzheimer's disease, phosphomonoesters (PMEs) including
      phosphocholine (P-choline) are present at elevated levels. PMEs also are elevated
      in the developing brain during the period of neurite extension. To determine if
      the elevation of PMEs in AD could reflect neuritic sprouting, 31P-NMR was used to
      examine phospholipid metabolites and membrane phospholipids at various times
      following unilateral lesions of the entorhinal cortex, a well-defined model of
      neuritic sprouting. Two to 7 days postlesion, P-choline levels were elevated 48%
      in the hippocampus ipsilateral to the entorhinal cortex lesion, but not in the
      contralateral hippocampus or cerebral cortex. P-choline levels declined by day
      15, and reached control levels 45 days following the lesion. The lesion-induced
      elevation in P-choline could result from increased P-choline synthesis via
      choline kinase, decreased activity of CTP:phosphocholine cytidylyltransferase, or
      breakdown of phosphatidylcholine (PC). To distinguish between these
      possibilities, the membrane phospholipids PC and phosphatidylethanolamine (PE)
      were measured. Both phospholipids were maintained at or above control levels at
      each of the postlesion time points, arguing against membrane breakdown or
      decreased PC synthesis contributing to the elevation of P-choline levels. Other
      alterations included a widespread elevation in inositol phosphate 2 days
      postlesion, but not at later time points. The alterations in phospholipid
      metabolites observed in the rat hippocampus following entorhinal cortex lesions
      closely resemble those observed in the human brain in the early stages of AD.

PMID- 9263197
TI  - Long-term treatment of male F344 rats with deprenyl: assessment of effects on
      longevity, behavior, and brain function.
AB  - L-Deprenyl (selegiline) was chronically administered to male Fischer 344 rats via
      their drinking water beginning at 54 weeks of age (estimated daily dose: 0.5
      mg/kg/day). Beginning at 84 weeks of age, the rats were behaviorally evaluated
      using a sensorimotor battery, a motor-learning task, and the Morris water maze.
      At 118 weeks of age, cerebellar noradrenergic function was evaluated in the
      surviving rats using in vivo electrochemistry. The rats were then sacrificed to
      measure brain monoamine oxidase activity and perform quantitative autoradiography
      to evaluate the effect of chronic deprenyl treatment on beta-adrenergic receptors
      in the cerebellum, alpha 2-adrenergic receptors several brain regions, and D1 and
      D2 dopamine receptors in the striatum. Deprenyl treatment reduced brain monoamine
      oxidase B activity by 85%, but had no effect on brain monoamine oxidase A. A
      clear effect of chronic deprenyl treatment upon longevity was not observed.
      Several measures of CNS function were altered in the deprenyl-treated animals: 1)
      spatial learning in the Morris water maze was improved; 2) electrochemical
      signals recorded following local application of NE were reduced, and the
      responsiveness to the reuptake blocker nomifensine was enhanced, in the
      cerebellum; 3) beta-adrenergic receptor binding affinity was increased in the
      cerebellum; 4) alpha 2-adrenergic receptor density was increased in the inferior
      colliculus; and 5) striatal D1 dopamine receptor density was reduced but binding
      affinity was enhanced. In contrast, chronic deprenyl treatment did not cause
      changes in: 1) sensorimotor function, as evaluated by balance beam, inclined
      screen, or wire hang tasks; 2) motor learning; 3) alpha 2-adrenergic receptor
      density in any region examined except for the inferior colliculus, or binding
      affinity in any region examined; or 4) striatal D2 dopamine receptor number or
      affinity. Thus, long-term oral administration of deprenyl extended the functional
      life span of rats with respect to cognitive, but not motor, performance.

PMID- 9263198
TI  - Neurochemical changes in the hippocampus of the brown Norway rat during aging.
AB  - Microdensitometrical and stereological techniques were applied to study the
      effects of aging on the hippocampus of 3-, 6-, 12-, 18-, 24-, 30-, and 36-month
      old male Brown Norway rats. Stereological analysis of basic fibroblast growth
      factor (bFGF) immunoreactive glial cells in the CA1 area showed an age-dependent
      decrease in the number of cells, starting at 18 months of age. Specific mean gray
      values of the immunoreactivity for bFGF were reduced in the CA3 area, in the
      dentate gyrus, and in fields of the CA1 area, starting at 24 months of age. There
      were no differences between the age groups in the number of glial fibrillary
      acidic protein or glucocorticoid receptor (GR) immunoreactive cells of the CA1
      CA2 areas. However, the intensity of the GR immunoreactivity was decreased in the
      18-month-old and older rats. No changes in the immunoreactivity for the
      mineralocorticoid receptor were observed in the CA1-CA2 areas of any of the age
      groups. Spontaneous alternation test and reactivity in an open field did not
      reveal marked differences between the age groups. These findings give evidence
      that there is a loss of neural GR immunoreactivity, but no loss of GR
      immunoreactive neurons, in the CA1-CA2 areas of the aged Brown Norway rat. Aging
      may also be characterized by substantial deficits of glially derived growth
      factors, such as bFGF in the hippocampus. The changes in immunoreactivities were
      not correlated to alterations in selected behaviors dependent on normal
      hippocampal function.

PMID- 9263199
TI  - N-methyl-D-aspartate receptor binding in brains of rats at different ages.
AB  - Potential age differences in N-methyl-D-aspartate (NMDA) receptor binding were
      evaluated in rat brain using [3H]dizocilpine and [3H]D,L-(E)-2-amino-4-propyl-5
      phosphono-3-pentanoic acid (CGP 39653) as the radioligands. Neither
      [3H]dizocilpine nor [3H]CGP 39653 binding in hippocampus revealed any age
      difference (7 vs. 23-25 months) in Bmax or Kd. High-affinity [3H]dizocilpine
      binding showed a developmental increase (8 vs. 2 months) in hippocampus but not
      in frontal cortex. No senescence-related change (25 vs. 8 months) was observed in
      either region. The lack of senescence-related differences in these biochemical
      markers does not preclude the possibility of functional changes in the NMDA
      receptor with aging.

PMID- 9263200
TI  - Expression of alpha 4-1 and alpha 5 nicotinic cholinoceptor mRNA in the aging rat
      cerebral cortex.
AB  - Although important in neurodegeneration, systematic studies of nicotinic
      acetylcholine receptor expression in normal aging human brains are difficult to
      perform. We have studied the expression of nicotinic receptor alpha 4-1 and alpha
      5 mRNA in the frontal and parietal isocortex of 3- (young adult), 24- (late
      middle aged), and 33-month-old (old) rats by nonisotopic in situ hybridization.
      In all groups transcripts were mainly present in layer II/III and V pyramidal
      neurons. The numerical densities of alpha 4-1 mRNA-containing neurons with
      respect to those of cresyl violet-stained neurons decreased with aging in the rat
      frontal and parietal cortex, while those of alpha 5 mRNA-containing neurons were
      not affected. These findings point to an age-related decrease of the percentages
      of numerical densities of alpha 4-1 mRNA-containing neurons, which has to be
      taken into account as a possible substrate for the well-known decrease of
      nicotine binding sites in the aging cerebral cortex.

PMID- 9263201
TI  - Interleukin-1 beta inhibits glutamate release in hippocampus of young, but not
      aged, rats.
AB  - The proinflammatory cytokine, interleukin-1, is synthesized in neuronal and glial
      cells and is released in response to stress/injury. IL-1 exerts profound effects
      on the central nervous system, which include an inhibitory effect on synaptic
      activity in hippocampus, a brain area expressing a high density of IL-1
      receptors. We report that IL-1 beta has an inhibitory effect on KCl-stimulated
      release of glutamate and KC1-stimulated [45Ca] influx in synaptosomes prepared
      from hippocampus of 4-month-old rats. These effects were inhibited by the
      endogenous receptor antagonist, IL-1ra, and by the phospholipase A2 (PLA2)
      inhibitor, quinacrine, suggesting that IL-1 receptor activation is coupled to
      PLA2. An inhibitory effect of IL-1 beta on protein kinase C activity was also
      observed. KC1-induced calcium-dependent release and calcium influx, and protein
      kinase C activity were significantly decreased in hippocampal synaptosomes
      prepared from 22-month-old compared to 4-month-old animals. In contrast to the
      inhibitory effect of IL-1 beta in synaptosomes prepared from young adult animals,
      no effect was observed on release, calcium influx, or protein kinase C activity
      in synaptosomes prepared from aged animals. We report that there is an age
      related increase in expression of IL-1 beta in hippocampus and propose that this
      change may underlie the attenuated responses to IL-1 beta in hippocampus of aged
      animals.

PMID- 9263202
TI  - Distribution of estrogen receptor-beta-like immunoreactivity in rat forebrain.
AB  - The data presented here are the first to describe the distribution of estrogen
      receptor-beta (ER beta)-like immunoreactivity in brain tissue. We employed an
      affinity purified rabbit antiserum made against a portion of the C-terminal of
      the ER beta protein. The majority of ER beta-like immunoreactive (ER beta-ir)
      neurons were found in the following regions: lateral septum, bed nucleus of the
      stria terminalis, paraventricular nucleus, supraoptic nucleus, medial amygdala,
      the dentate gyrus and the CA1 and CA2 fields of the hippocampus. A few ER beta-ir
      neurons were noted in the anterior hypothalamus, periventricular nucleus, medial
      preoptic area, and in the arcuate nucleus. All of the immunoreactivity appeared
      nuclear in its subcellular distribution, with the exception of the cells in the
      lateral septum, CA1 and CA2. In these areas immunoreactivity was noted throughout
      the perikarya and in cell processes. The data suggest that ER beta mediates
      estrogen's actions in a subset of hypothalamic and limbic neurons.

PMID- 9263203
TI  - Histamine and prostaglandin interaction in the central regulation of ACTH
      secretion.
AB  - Since prostaglandins (PGs) and histamine (HA) seem to be involved in the
      activation of the hypothalamic-pituitary-adrenal axis following immunochallenges
      with lipopolysaccharide (LPS) endotoxin and cytokines, we investigated whether
      the histaminergic and eicosanoid systems in the male rat brain interact in their
      regulation of ACTH secretion. The PG synthesis inhibitor indomethacin (10 mg/kg
      i.p.) attenuated the ACTH response to LPS (10 micrograms/kg i.p.) and HA (30
      micrograms i.c.v.). Infusion of PGE1, PGE2 or PGF2 alpha (1 and/or 5 micrograms
      infused intracerebroventricularly) stimulated ACTH secretion. The ACTH response
      to PGE1 was inhibited by the HA synthesis inhibitor alpha-fluoromethyl-histidine
      and the H1 receptor antagonist mepyramine (MEP) but not the H2 receptor
      antagonist cimetidine (CIM). Neither MEP nor CIM affected the ACTH response to
      PGE2. MEP and CIM attenuated the ACTH response induced by PGF2 alpha. The
      findings indicate that HA and some PGs in the brain interact in their stimulatory
      regulation of ACTH secretion. Such an interaction may also be involved in their
      mediation of the ACTH response to immunochallenges.

PMID- 9263204
TI  - Central administration of the neurotensin receptor antagonist, SR48692, modulates
      diurnal and stress-related hypothalamic-pituitary-adrenal activity.
AB  - Previous studies in our laboratory suggest that neurotensin (NT) acts centrally
      to modulate adrenocorticotropin hormone (ACTH) and corticosterone release. In the
      present studies, we examined hypothalamic-pituitary-adrenal (HPA) function under
      basal conditions and during restraint stress following central administration of
      the highly specific NT receptor antagonist, SR48692. Chronic delivery of SR48692
      to the paraventricular nucleus (PVN) of the hypothalamus via indwelling central
      cannulae attenuated both the diurnal- and stress-induced elevations in HPA
      activity. Thus, SR48692 decreased the diurnal increase in plasma ACTH and
      corticosterone during the evening phase of the cycle, but did not affect morning
      levels. Restraint-induced increases in plasma ACTH and corticosterone levels were
      also significantly reduced in the SR48692-implanted animals. This suggests that
      the inhibitory effects of SR48692 were restricted to periods of stimulated HPA
      activity. A decrease in corticotropin-releasing hormone (CRH)-like
      immunoreactivity was observed within the PVN following chronic SR48692, and
      parallel decreases in CRH-like immunoreactivity were observed within the external
      zone of the median eminence. These findings suggest that endogenous NT serves to
      increase HPA activity during periods of enhanced stimulation.

PMID- 9263205
TI  - Glucocorticoids inhibit stress-induced phosphorylation of CREB in corticotropin
      releasing hormone neurons of the hypothalamic paraventricular nucleus.
AB  - The corticotropin-releasing hormone (CRH) gene contains a perfect palindromic
      motif in its promoter region that allows binding of the cyclic adenosine
      monophosphate response element binding protein, CREB. Since previous studies
      suggest that the CRH gene can be activated by cyclic adenosine monophosphate, we
      determined whether stress and feedback inhibition by glucocorticoids in CRH
      producing neurons in the hypothalamic paraventricular nucleus could be mediated
      by changes in the phosphorylation of CREB. Antisera to CREB and phospho-CREB
      Ser133 (PCREB), the active phosphorylated form of CREB, were used for
      immunohistochemical studies on rat brain. In nonstressed animals CREB
      immunostaining was confined to the nucleus of cells ubiquitously throughout the
      hypothalamus, while PCREB immunostaining was discretely localized in
      magnocellular neurons and only a few cells in the medial parvocellular
      subdivision of the paraventricular nucleus. Ether and handling stress markedly
      increased the number of PCREB-labeled neurons in the parvocellular subdivision.
      Double immunolabeling with CRH antiserum revealed that the majority of
      hypophysiotropic CRH neurons in stressed animals expressed PCREB. Following
      systemic administration of dexamethasone (100 micrograms/day) for 2.5 days, PCREB
      immunostaining was completely abolished in parvocellular CRH-producing neurons
      after ether or handling stress. Dexamethasone had no apparent effect on CREB
      immunostaining. These results demonstrate that glucocorticoids suppress CREB
      phosphorylation in hypophysiotropic CRH neurons and suggest that prevention of
      CREB phosphorylation is a possible mechanism for feedback inhibition of CRH
      biosynthesis by glucocorticoids.

PMID- 9263206
TI  - Effect of cholinergic blockade on glucocorticoid regulation of NPY and
      catecholamines in the rat adrenal gland.
AB  - Catecholamines and neuropeptide Y (NPY) levels were determined in the adrenals of
      rats treated for 2.5 days with chlorisondamine (6 mg/day), a nicotinic ganglionic
      blocking agent, metyrapone (66 mg/day), an inhibitor of the 11 beta-hydroxylase
      activity or both metyrapone and chlorisondamine. Chlorisondamine induced a
      significant increase in adrenal weight (31%) without significant rise in
      hypothalamic CRH content, plasma ACTH level and plasma corticosterone
      concentration. This drug was unable to affect significantly dopamine (DA),
      norepinephrine (NE) and epinephrine (E) content of the adrenals; in contrast, it
      induced a significant decrease (90%) of plasma NE and E levels. Chlorisondamine
      induced no change in adrenal NPY content as well as NPY mRNA level determined by
      Northern blot but significantly increased NPY plasma level. Metyrapone-treatment
      induced a significant drop of plasma corticosterone level and elicited a
      significant reduction of hypothalamic CRH content, a rise (460%) of the plasma
      ACTH concentration associated with a significant increase (18%) of the adrenal
      weight. A marked increase of DA (240%) and significant decrease of E (22%) in the
      adrenal gland were observed in response to metyrapone treatment. In addition,
      metyrapone induced a drop (23%) in plasma E level. In both the adrenals and the
      plasma, the ratio E/NE was significantly reduced by metyrapone treatment.
      Metyrapone elicited a significant increase of adrenal NPY content (88%) as well
      as of NPY mRNA revealed by Northern blot analysis but was unable to significantly
      affect NPY plasma level. The effects of chlorisondamine, given in combination
      with metyrapone on both hypothalamic CRH content and plasma ACTH level, were
      similar to those induced by metyrapone given alone. Chlorisondamine-mediated
      pharmacological ganglionic blockade increased metyrapone-induced adrenal
      hypertrophy and adrenal DA storage but prevented metyrapone-induced depletion of
      adrenal E as well as increase of the adrenal NPY mRNA level and NPY content.
      Chlorisondamine-induced elevation of plasma NPY level was not observed under
      metyrapone treatment. Present data suggest that the increase in adrenal NPY
      synthesis in response to metyrapone treatment is mediated by transsynaptic
      cholinergic activation and implies nicotinic receptors. On the other hand,
      adrenal TH may be regulated by additional or different mechanisms, which possibly
      involve nonnicotinic transmission. Present work also suggests that the
      suppression of the glucocorticoid feedback inhibition of hypothalamic CRH neurons
      could stimulate sympathoneuronal outflow and consequently elicit transsynaptic
      cholinergic activation of adrenal neuropeptide Y gene expression.

PMID- 9263207
TI  - Sauvagine and TRH differentially stimulate proopiomelanocortin biosynthesis in
      the Xenopus laevis intermediate pituitary.
AB  - In the amphibian Xenopus laevis, adaptation of the skin color to background light
      intensity is regulated by alpha-melanophore-stimulating hormone (alpha-MSH), a
      proopiomelanocortin (POMC)-derived peptide. In animals adapted to a white
      background, the level of POMC biosynthesis in the intermediate pituitary is much
      lower than in animals adapted to a black background. Release of alpha-MSH from
      neurointermediate lobes of white-adapted animals is stimulated in vitro by the
      regulatory peptides sauvagine and thyrotropin-releasing hormone (TRH), which are
      produced in the magnocellular nucleus of the hypothalamus. To study the role of
      sauvagine, cAMP, TRH and phorbol 12-myristate 13-acetate (PMA) in the regulation
      of POMC biosynthesis, the degree of incorporation of radioactive amino acids into
      the POMC protein was determined after treatment of the neurointermediate lobes
      with these secretagogues. When lobes of white-adapted animals are incubated in
      vitro, biosynthetic activity spontaneously increases because hypothalamic
      inhibitory control is removed by dissection. In addition to this control
      situation, the effects of secretagogues were tested on lobes with an inhibited
      level of biosynthesis, which is achieved by addition of neuropeptide Y (NPY) to
      the incubation medium. After 24 h of treatment, TRH stimulated POMC biosynthesis
      in NPY-inhibited lobes of white-adapted animals from 40.2 to 95.3% of control
      level. This stimulation could not be reduced by adding PMA, which indicates that
      protein kinase C is not involved in the stimulation of POMC biosynthesis by TRH.
      Sauvagine partially restored POMC biosynthesis from 27.2 to 62.5% of control
      level, whereas 8-Br-cAMP completely counteracted NPY inhibition from 27.8 to
      97.5% of control level. After 3 days of treatment, stimulation by sauvagine and 8
      Br-cAMP was maintained (sauvagine increased POMC biosynthesis in NPY-inhibited
      lobes from 7.4 to 36.2% of control level and 8-Br-cAMP stimulated from 6.5 to
      82.5% of control level). TRH had no effect on POMC biosynthesis after 3 days of
      treatment, although its receptor was still functional as was shown in superfusion
      experiments where TRH stimulated alpha-MSH secretion. The observations indicate
      that the neuropeptides sauvagine and TRH differently control POMC biosynthesis in
      the Xenopus intermediate pituitary. This differential regulation is not only
      apparent with regard to time aspects (sauvagine has a sustained regulatory
      function, whereas TRH is only effective in the initial phase of POMC biosynthesis
      stimulation), but also an uncoupling of biosynthetic and release processes could
      be shown for TRH, which did not occur with sauvagine.

PMID- 9263208
TI  - Dual effect of electrochemical stimulation of the medial preoptic area on the
      release of LH: possible neurotransmitter involvement.
AB  - Electrochemical and electrical stimulation of the medial preoptic area (MPA) was
      shown to induce release of LH in rats. Owing to differences in cytoarchitecture
      and neural afferents between the medial (mMPA) and lateral (lMPA) parts of the
      MPA, we decided to explore whether this difference in organization would
      distinctly influence the secretion of gonadotropin. Both parts of the MPA were
      electrochemically stimulated on the day of proestrus in freely behaving rats
      bearing chronic implanted electrodes. An anodic direct current of 100 microA was
      delivered for 40 s at 11.00 h and blood samples were obtained every hour until
      17.00 h. Serum LH concentrations in rats stimulated in the medial part of the MPA
      showed a robust rise 1 h after the stimulus was applied and the values remained
      high up to the end of the bleeding period. All these animals ovulated. An initial
      rise in serum LH was also seen in rats stimulated in the lMPA but serum values
      thereafter returned to basal levels, significantly lower than those in the mMPA
      stimulated or in control, nonstimulated rats. Only 2 rats showed full ovulation
      and the others failed to ovulate or had partial ovulation. Injection of the
      serotonin antagonist, methysergide, did not affect the response of rats
      stimulated in either the mMPA or lMPA. The GABA antagonist, bicuculline, had no
      effect on LH release evoked by lMPA stimulation but blocked the release induced
      by mMPA stimulation. This later blockade was partially reversed by the
      administration of the opioid receptor antagonist, naloxone, suggesting the
      existence of GABA facilitatory influences on LH release via inhibition of
      opioidergic inputs to the GnRH neurons. On the other hand, naloxone
      administration had no effect on LH release evoked by stimulation of the mMPA but
      partially reversed the inhibition resulting from stimulating the lMPA. These data
      indicate that the mMPA and lMPA have opposite effects on LH secretion and provide
      evidence for the possible neurotransmitters involved.

PMID- 9263209
TI  - Expression of glutamate receptor subunit mRNAs in gonadotropin-releasing hormone
      neurons during the sexual maturation of the female rat.
AB  - Excitatory amino acids, particularly glutamate, are thought to be important for
      the maturation of the brain-pituitary-gonadal axis and the induction of puberty
      in the rat. We have previously shown that, in the female rat, GnRH neurons
      preferentially express the KA2 and NMDAR2A receptor subunit mRNAs, but not AMPA
      or NMDAR1 mRNA. The aim of the present study was to determine whether the onset
      or rate of KA2 and NMDAR2A receptor expression in GnRH neurons is correlated with
      the onset of puberty. Dual in situ hybridization using digoxigenin-labeled GnRH
      cRNA probes and 35S-labeled glutamate receptor subunit probes, followed by
      autoradiography and image analysis were used to measure the KA2 or NMDAR2A mRNA
      content in GnRH neurons in 20- to 50-day-old female rats which were sacrificed at
      08.00 or 17.00 h. The results show that: (a) the KA2 mRNA content of GnRH neurons
      and the number of GnRH neurons expressing KA2 mRNA increase progressively in the
      morning hours between postnatal days 20 and 40; (b) the diurnal pattern of KA2
      mRNA levels in GnRH neurons changes between days 40 and 50 from high KA2 levels
      in the morning hours before day 40 to high KA2 mRNA levels in the afternoon in 45
      and 50-day-old animals; (c) while the high levels of KA2 mRNA in GnRH neurons in
      the morning hours of 20- to 40-day-old animals are paralleled by an overall
      increase in KA2 expression in the preoptic area, the rise in KA2 mRNA in GnRH
      neurons in the afternoon of 45- and 50-day-old animals appears to be specific for
      the GnRH neurons, and (d) no significant differences were detected for the
      NMDAR2A mRNA content in GnRH neurons among the different age groups and the
      morning and afternoon values. Since the gradual increase in the KA2 mRNA content
      in GnRH neurons of animals reaching puberty as well as the reversal of diurnal
      rhythmicity in KA2 receptor mRNA content of GnRH neurons coincide with the times
      of vaginal opening and first ovulation, it is suggested that glutamate, acting
      through KA2 receptors directly on GnRH neurons is, at least in part, an important
      factor in the excitatory regulation of the postnatal sexual development of the
      female rat. In contrast, expression of the NMDA-preferring receptor, NMDAR2A, in
      GnRH neurons appeared to be unchanged during this development.

PMID- 9263210
TI  - Vasopressin acts in the subfornical organ to decrease blood pressure.
AB  - In addition to its traditional role as a circulating vasoactive peptide,
      vasopressin (VP) has been shown to play significant roles in central
      cardiovascular processing. The recent description of VP receptors within the
      subfornical organ (SFO) has suggested this circumventricular organ (CVO) as a
      potential locus for feedback actions of circulating VP on the brain. The well
      established anatomical connections between SFO and hypothalamic autonomic control
      centers provide further arguments in support of such a view. This study was
      undertaken to determine the physiological consequences of activation of VP
      receptors within the SFO of urethane anesthetized rats. Microinjection (0.5
      microliter) of 5 pmol VP into SFO resulted in significant decreases in blood
      pressure (BP, mean AUC -638.3 +/- 110.3 mm Hg.s, p < 0.01, n = 13) without a
      change in heart rate (HR, mean AUC 7.9 +/- 14.0 beats, p > 0.05, n = 12), effects
      which were repeatable. These depressor effects were specific to microinjection
      locations within this CVO as similar VP microinjections into non-SFO tissue were
      without effect on BP (mean AUC 245.4 +/- 111.5 mm Hg.s, p > 0.05, n = 10), or HR
      (mean AUC 1.8 +/- 3.1 beats, p > 0.05, n = 9). In contrast to the former
      depressor effects, VP microinjection (5 pmol in 0.5 microliter) into the third
      ventricle produced large increases in BP (mean AUC 1,461.8 +/- 368.97 mm Hg.s, p
      < 0.05, n = 6) again with no change in HR (mean AUC 1.4 +/- 5.96 beats, p > 0.05,
      n = 6). The hypotensive effects observed in response to VP microinjection into
      SFO were abolished by systemic treatment with a V1 receptor antagonist (mean AUC
      89.5 +/- 67.7 mm Hg.s, p > 0.05) compared to BP response before V1 receptor
      blockade (mean AUC -605.9 +/- 119.8 mm Hg.s, n = 4). These results suggest that
      the SFO may be an essential structure in the feedback control loop through which
      circulating VP influences descending autonomic pathways involved in
      cardiovascular control.

PMID- 9263211
TI  - NG-methyl-L-arginine, an inhibitor of nitric oxide synthase, affects the central
      nervous system to produce peripheral hyperglycemia in conscious rats.
AB  - To determine whether the nitric oxide (NO) system in the central nervous system
      (CNS) is involved in the peripheral metabolism of carbohydrate we injected NG
      methyl-L-arginine (L-NMA), an inhibitor of NO synthase, into the third cerebral
      ventricle of unanesthetized, unrestrained rats and determined the plasma level of
      glucose. This intracerebroventricular (i.c.v.) injection of the drug increased
      the plasma level of glucose dose-dependently, whereas an intravenous (i.v.)
      injection had no effect. The hyperglycemia thus induced was suppressed by
      concomitant i.c.v. or prior i.v. administration of L-arginine. Concomitant
      administration of D-arginine did not affect hyperglycemia by L-NMA. The i.c.v.
      injection of 5 x 10(-6) mol L-NMA increased plasma levels of glucose, epinephrine
      and norepinephrine, and serum levels of glucagon. However, plasma levels of
      insulin were unchanged, despite the presence of hyperglycemia. The hyperglycemia
      produced by L-NMA was completely inhibited by bilateral adrenalectomy. It was
      also inhibited by prior intraperitoneal injection of phentolamine, but not of
      propranolol or naloxone. Results suggest that L-NMA acts on the CNS to stimulate
      adrenal secretion of epinephrine and, subsequently, to elevate glucose levels in
      the peripheral blood. The NO system thus seems to be involved in the neural
      regulation of the adrenal by the GNS, which in turn regulates peripheral blood
      glucose levels.

PMID- 9263212
TI  - Therapeutic prospects for fibroblast growth factor treatment of brain ischemia.
AB  - Ischemic stroke causes neurological disability in millions of people worldwide
      each year. At present, standard therapies are often ineffective in stroke
      prevention. In this review, we summarize recent findings on the role of
      fibroblast growth factors in neuroprotection after experimental brain ischemia.

PMID- 9263213
TI  - The predictive value of ventricular CSF removal in normal pressure hydrocephalus.
AB  - We report the impact of diagnostic ventricular CSF removal (VCR) on the gait
      disturbance in 24 patients with suspected normal pressure hydrocephalus (NPH) who
      had an intraventricular catheter for studies of CSF dynamics in order to select
      patients for shunt surgery. There were no complications related to removal of 24
      ml CSF over a period of 6 hours in four instances or to the removal of 15-18 ml
      at one time in twenty instances. Seventeen out of 24 patients were diagnosed as
      having NPH. Two of those patients who had relatively mild symptoms had a
      prolonged amelioration of their gait disturbance after diagnostic VCR. Thirteen
      patients underwent subsequent shunt operations. Eleven of them had good
      functional and symptomatic improvement on follow-up. In those six patients who
      had a marked amelioration of their gait disturbance after diagnostic VCR, not
      only improvement of the gait disturbance was observed after shunting, but a
      consistent overall improvement as well. The predictive value of VCR was more
      variable in those six patients who had only a moderate response to VCR. No change
      of the gait disturbance after VCR was noted in seven patients in whom the
      diagnosis of NPH was not confirmed. Diagnostic VCR might be a valuable ancillary
      test in specialized centers which routinely use intraventricular CSF monitoring
      in the selection of patients for shunt surgery.

PMID- 9263214
TI  - Extracellular glial fibrillary acidic protein and amino acids in brain regions of
      patients with subarachnoid hemorrhage--correlation with level of consciousness
      and site of bleeding.
AB  - The extracellular fluid of two cortical regions was investigated in eight
      patients who underwent surgery for subarachnoid hemorrhage within 7-96 h after
      the rupture of an arterial aneurysm. Microdialysis samples, collected from the
      cortex of the ipsilateral gyrus rectus and temporal lobe for 52-127 h, were
      analyzed with respect to amino acids and the glial fibrillary acidic protein. In
      agreement with a previous study, an inverse relation was observed between total
      amino acid concentration and the level of consciousness. We also found that the
      concentration of glial fibrillary acidic protein was higher close to the bleeding
      site. Furthermore, we observed specific changes in the concentration of the
      protein and certain amino acids which coincided with clinical events such as
      increased intracranial pressure, vasospasm, ischemia and infarction. Finally, the
      concentrations of taurine may corroborate its function as an osmoequivalent.

PMID- 9263215
TI  - Effect of tumor necrosis factor-alpha on the permeability of bovine brain
      microvessel endothelial cell monolayers.
AB  - The administration of chemotherapy to patients with tumors of the central nervous
      system is often blocked by the blood-brain barrier. Tumor necrosis factor-alpha
      (TNF-alpha) is a cytokine that promotes vascular permeability in addition to its
      pro-inflammatory effects. However, no direct evidence exists as to whether TNF
      alpha may increase permeability of the BBB. We evaluated the effect of TNF-alpha
      on the transport of cisplatin (CDDP) or high molecular weight dextran labeled
      with fluorescein isothiocyanate (FITC-dextran) across bovine brain microvessel
      endothelial cell (BMEC) monolayers that was conducted on side-by-side diffusion
      chambers in vitro. The permeability coefficient for the transport of CDDP across
      the untreated monolayer was 3.80 x 10(-5) cm sec-1 at 30 minutes. After treating
      the BMEC monolayer with TNF-alpha (50 U ml-1 and 500 U ml-1) for 36 hours, the PC
      of CDDP increased significantly to 8.94 x 10(-5), and 14.43 x 10(-5) cm sec-1
      respectively (p < 0.01). TNF-alpha had no effect on the transport of FITC-dextran
      across the BMEC monolayers. Electron microscopy showed that the tight junctions
      between the BMECs persisted even after treatment with TNF-alpha, whereas they had
      been partially disrupted following exposure to mannitol, 1600 mOsm kg-1. TNF
      alpha selectively promoted the in vitro permeability of the blood-brain barrier
      to CDDP without disrupting tight junctions. This system could be used as a model
      for experimental studies of chemotherapy. Findings suggested that the combined
      administration of TNF-alpha and CDDP may be clinically useful.

PMID- 9263216
TI  - Stroke recurrence among 30 days survivors of ischemic stroke in a prospective
      community-based study.
AB  - A cohort of 209 patients (105 men and 104 women), who survived 30 days after
      'first ever-in-lifetime ischemic stroke' were followed for one year. Predictors
      of survival were examined by log-rank test and Cox proportional hazards method.
      Twenty-four patients had a stroke recurrence (11.4%). Thirteen of the patients
      with recurrent stroke (54%) died because of the sequelae of the second stroke.
      Stroke recurred in 16% of patients with stroke due to atherosclerosis, in 12.5%
      of patients with cardioembolic stroke, and in 4.4% of patients with lacunar
      stroke. The life table cumulative risk of death at 6 and 12 months for patients
      with recurrent stroke was statistically higher (22% and 57%) than patients
      without recurrent stroke (13% and 29% respectively). History of untreated
      hypertension prior to the initial stroke (RR = 1.7, 95% Cl 1.2-4.1, p < 0.05) was
      an independent predictor of recurrence. In 134 patients (64.9%) aspirin was
      initiated during the first month after stroke. Only 81 patients (39.8%) continued
      aspirin treatment for the whole year. Life table cumulative risk of mortality
      among the patients treated with aspirin was 8% at 6 months and 12% at 1 year
      compared to 19% at 6 months and 45% at 12 months for those untreated with
      aspirin. We conclude that the high risk of recurrent stroke in Poland could be
      redaced by increased use of anti-platelets therapy and anti-hypertensive therapy
      after ischemic stroke.

PMID- 9263217
TI  - Comparison of ultrasonic and histopathological features of carotid artery
      stenosis.
AB  - Besides the degree of carotid artery stenosis, the composition of the plaque may
      help to predict the thromboembolic risk. Low echogenicity on ultrasound and
      hemorrhage into the atheroma demonstrated histopathologically have been shown to
      be associated with a higher risk of embolism. Twenty-nine consecutive patients
      with carotid artery stenosis and scheduled for carotid endarterectomy were
      investigated preoperatively by B-mode ultrasound. Post-operatively the
      endarterectomy specimens were examined histopathologically. Neither atheroma with
      hemorrhage nor atheroma without hemorrhage were significantly associated with
      echolucent ultrasound presentation. Out of the 10 lesions echolucent and
      homogeneous on ultrasound, six corresponded to atheroma with hemorrhage, two
      corresponded to atheroma with hemorrhage plus thrombus, two corresponded to
      fibrous plaque plus thrombus, and one corresponded to pure thrombus. Out of the 4
      lesions heterogeneous and predominantly echolucent, one corresponded to atheroma
      without hemorrhage plus thrombus, one corresponded to atheroma with hemorrhage,
      one corresponded to atheroma with hemorrhage plus thrombus, one corresponded to
      atheroma with hemorrhage plus fibrous plaque. Seven out of the 18 atheromas with
      hemorrhage did not present as purely or predominantly echolucent lesions, six of
      them were even homogeneously echogenic. Plaque surface could not reliably be
      predicted by ultrasound. In our study, there was no significant correlation
      between ultrasound and histology of the lesion.

PMID- 9263218
TI  - The outcome of early surgical management of ruptured posterior circulation
      aneurysms.
AB  - Since 1990, early surgery within 3 days following subarachnoid hemorrhage has
      been performed routinely in our hospital even for ruptured posterior circulation
      aneurysms. Our experience with early surgical management of 25 patients with
      posterior circulation aneurysms, including two patients who underwent
      endovascular surgery, is reported. Fourteen patients had an aneurysm on the
      basilar, the posterior cerebral or superior cerebellar artery (BA), and 11
      patients had an aneurysm on the vertebral or posterior inferior cerebellar artery
      (VA). The mortality and morbidity of the BA group were 7% and 29%, respectively,
      and those of the VA group were 27% and 9%, respectively. In BA, the incidence of
      symptomatic vasospasm and hydrocephalus was definitely high compared with VA, and
      the outcome in elderly patients was significantly unfavorable. Early surgery for
      posterior circulation aneurysms to prevent rebleeding might be considered in
      selected cases.

PMID- 9263219
TI  - Bromocriptine prevents neuron damage following inhibition of superoxide dismutase
      in cultured ventral spinal cord neurons.
AB  - Rosen et al. have reported point mutations in the cytosolic Cu/Zn superoxide
      dismutase (SOD 1) gene in some families with familial amyotrophic lateral
      sclerosis (ALS). To determine whether decreased SOD activity could contribute to
      neuronal damage, rat embryo ventral spinal cord neurons were incubated with
      diethyldithiocarbamate (DDC), an inhibitor of SOD. There was a marked increase in
      neuronal damage in cultures exposed to DDC and this phenomenon was dose-related.
      In this paradigm, these deteriorative changes were prevented by bromocriptine.
      DDC-treated ventral spinal cord neurons provide an in vitro model of free radical
      neurotoxicity secondary to decreased SOD activity. Simultaneous treatment with
      bromocriptine and DDC reduced neurotoxicity, indicating that bromocriptine has a
      neuroprotective effect against free radicals.

PMID- 9263220
TI  - Evaluation of cerebral autoregulation following diffuse brain injury in rats.
AB  - The normal cerebral circulation has the ability to maintain a stable cerebral
      blood flow over a wide range of cerebral perfusion pressures and this is known as
      cerebral autoregulation. This autoregulation may be impaired in the injured
      brain. Closed head injury was induced in 28 Sprague-Dawley rats weighing 400-450
      g. Four groups were studied: control group, head injured rat from meter height
      using 350 g, 400 g and 450 g respectively. CBF, volume velocity was monitored
      using laser-Doppler flowmetry together with monitoring of ICP and arterial blood
      pressure. Correlation to assess the relationship between CBF and CPP was done in
      each animal every hour. If correlation coefficient was > 0.85 and CPP was within
      normal range, loss of autoregulation was hypothesized. Chi square test, ANOVA
      test and unpaired Student's t-test were done and significant level of p < 0.05
      was established. Mean CBF in injured rats was significantly lower than controls
      (p = 0.028) at the fifth hour. CBV was lower in the group of 450 g 1 m impact
      than in controls at 3 h (p = 0.04). Velocity in the group of all injured rats,
      was significantly lower than in controls at 3 h (p = 0.032) and at 4 h (p =
      0.027). Loss of autoregulation was seen during first four hours after trauma in
      all groups of rats who sustained injury. Statistical significant difference (p =
      0.041) in loss of autoregulation between injured and control animals was seen. No
      loss of autoregulation was observed in the control group. In conclusion CBF and
      CPP provide information about loss of autoregulation in diffuse brain injury.
      Decrease in CBF and increase of ICP is observed as a result of loss of cerebral
      autoregulation. Knowledge of loss of autoregulation could give important
      information and help in the management of head injured patients.

PMID- 9263221
TI  - Cerebral calcium fluxes and calcium homeostasis in the rat: a minimal model.
AB  - Disturbance of calcium homeostasis and unregulated increase in intracellular
      calcium have been implicated in cell damage and cell death in the central nervous
      system in particular. To determine the specific pathway(s) of cerebral Ca
      transport of importance in a pathophysiological situation, we have measured long
      term Ca flux in brain in vivo in rat, and developed a kinetic model incorporating
      physiologically relevant pathways of cerebral Ca transport. 45Ca was injected
      into a tail vein in conscious rats. Plasma 45Ca was monitored up to 4 days post
      injection and 45Ca uptake determined in samples of cerebrospinal fluid (CSF) and
      at several sites of brain at euthanasia. Uptake of the tracer by tissues peaked
      after 1 h, isotopic equilibration taking longer. The uptake at hippocampus was
      the highest. Computer simulation of the kinetics of the plasma, CSF and tissue
      data was performed using a compartmental model, which included two
      subcompartments (intra- and extra-cellular) and two pathways from plasma to the
      brain: directly across the blood-brain barrier and via CSF, which included a
      delay. The analysis based on this model enabled estimation of the fractional
      rates of transport of Ca to cerebral and noncerebral tissues across all the
      barriers of the model.

PMID- 9263222
TI  - Endovascular suture occlusion of the middle cerebral artery in rats: effect of
      suture insertion distance on cerebral blood flow, infarct distribution and
      infarct volume.
AB  - Sprague-Dawley rats anesthetized with isoflurane, underwent MCA occlusion by
      intraluminal 3-0 suture insertion, either 22 mm (n = 8) or 18 mm (n = 6) beyond
      the CCA bifurcation or were sham-operated as controls (n = 3) for
      autoradiographic analysis of cerebral blood flow. Infarct volume was measured 24
      hours after the onset of ischemia (22 mm, n = 11; 18 mm, n = 10); neurological
      examinations were performed at 6 and 24 hours. Cerebral blood flow in the MCA
      distribution was significantly lower in the 22 mm suture insertion group than in
      the 18 mm group (p < 0.05). The total infarct volume was significantly larger
      (197 +/- 15 versus 135 +/- 19 mm3, p < 0.05) and the coefficient of variance was
      significantly smaller (23.8% versus 43.9%, p < 0.05) in the 22 mm group. Border
      zone regions of medial caudoputamen and dorsolateral cortex were often spared in
      the 18 mm group but never in the 22 mm group. The neurological deficit was more
      severe in the 22 mm group at 24 hours (p < 0.05), but not at 6 hours. The greater
      blood flow reduction and the less variable histological damage in dorsolateral
      cortex (a watershed area between the middle and anterior cerebral arteries) and
      the greater histological damage in medial caudate in the 22 mm group further
      characterizes this focal ischemia model for two potential applications: 22 mm
      insertion for studies requiring extensive and reproducible infarcts; 18 mm
      insertion for studies requiring less severe and more variable lesions after
      permanent MCA occlusion.

PMID- 9263223
TI  - Animal survival related to acute blood pressure response in global cerebral
      ischemia in rats.
AB  - The increase in mean arterial blood pressure (MABP) during global cerebral
      ischemia constitutes a compensatory and protective mechanism, regulated by the
      Central Nervous System, in response to the accumulation of different toxic
      compounds in the brain stem. The relationship between MABP increases and improved
      tolerance by the animals to ischemia is discussed.

PMID- 9263224
TI  - Identification of proliferating human anterior pituitary adenoma cells in vitro.
AB  - A method to determine whether dispersed human anterior pituitary adenoma cells
      proliferate in mixed culture was developed. Fifteen pituitary adenomas were
      dispersed enzymatically to single cells, following which twelve were double
      immunostained after eight days. Proliferating cells were identified
      immunologically following one hour of bromo-deoxyuridine incorporation. Adenoma
      cells were subsequently identified with an anti-neuron-specific enolase antibody
      system. A time course of bromo-deoxyuridine labelling was performed on three
      nonfunctional adenomas over a four day period, with bromo-deoxyuridine being
      added to cultures at one hour, 24 hours and four days prior to immunostaining.
      Double immunolabelled cells were unambiguously identified by a dark brown nucleus
      surrounded by red cytoplasm. Eight out of 12 pituitary adenomas (two
      prolactinomas, three nonfunctional, three growth hormone secreting) showed an
      increased bromo-deoxyuridine labelling index (range 0.1%-1.4%). Bromo
      deoxyuridine incorporation over four days showed an increase in bromo
      deoxyuridine from 0.02%, 0.03% and 3.3% at one hour to 10.1%, 1.3% and 5.0% at
      four days, respectively, but evidence of mitosis was scant. This study shows that
      pituitary adenomas may proliferate in vitro and that this double immunostaining
      method may be used as an in vitro proliferation assay in a mixed cell population.

PMID- 9263225
TI  - Effect of L-arginine and NG-nitro-L-arginine on delayed neuronal death in the
      gerbil hippocampus.
AB  - To assess the role of nitric oxide (NO) in cerebral ischemia, we investigated the
      effect of L-arginine, a substrate of NO synthase (NOS), and NG-nitro-L-arginine
      (L-NNA), a NOS inhibitor, on neuronal death in the CA1 hippocampal region.
      Seventy-two Mongolian gerbils were used in the study. Both carotid arteries were
      occluded for 4 min to induce forebrain ischemia. Temporal muscle temperature was
      strictly maintained at 37.5 +/- 0.3 degrees C during the ischemia. L-arginine (10
      and 100 mg kg-1) or L-NNA (1, 10 and 100 mg kg-1) was administered
      intraperitoneally 4 times: 30 min before, 3 h, 6 h and 24 h after induction of
      ischemia. Four days after ischemic insult, the animals were perfusion-fixed, and
      the neuronal densities in the medial, middle and lateral CA1 subfield were
      estimated. Average neuronal cell density of the control group was 2-3 mm in each
      subfield. L-arginine at doses of 10 and 100 mg kg-1 did not prevent neuronal
      death. L-NNA at doses of 1 and 10 mg kg-1 did not protect neuronal cells from
      ischemia either. However, in ischemia gerbils treated with 100 mg kg-1 L-NNA, the
      average neuronal cell density in the lateral CA1 subfield was 54.4 +/- 19.1, L
      NNA (100 mg kg-1) significantly (p < 0.05) reduced the occurrence of neuronal
      death in the lateral CA1 subfield. The present results suggest that NO plays an
      important role in the development of neuronal injury after global ischemia.

PMID- 9263226
TI  - Post-ischemic treatment with a lazaroid (U74389G) prevents transient global
      ischemic damage in rat hippocampus.
AB  - The ability of an experimental lazaroid, U74389G, to prevent damage to
      hippocampal CA1 cytoarchitecture due to transient global ischemia was studied by
      light and electron microscopy. Post-ischemic rats were given a single i.p. dose
      of lazaroid (6 or 18 mg kg-1) at 5 min after revival by cardiopulmonary
      resuscitation (CPR). Without lazaroid treatment the number of normal-appearing
      neurons in the CA1 region declined from a normal value of 15.49 +/- 2.21 to 8.40
      +/- 10.08 per 100 microns2 on day 7 after the ischemic episode, and there was
      extensive damage visible in the cytoarchitecture of this region. In lazaroid
      treated rats, the normal cytoarchitecture was retained and the number of normal
      appearing cells was maintained at 15.10 +/- 2.22 per 100 microns2. Ultrastructure
      studies indicated that pyknotic pyramidal cells laden with lysosomal aggregates
      were common in untreated post-ischemic rats but rare in lazaroid-treated rats.
      These results indicate that U74389G maintained the structural integrity of this
      region of the brain after transient global ischemia and suggest that this
      lazaroid may be an effective neuroprotectant.

PMID- 9263227
TI  - Experience with transcranial magnetic stimulation in cortical mapping.
AB  - Seventeen subjects underwent transcranial magnetic stimulation (TMS) toward
      cortical mapping. Cortical mapping produced scalp representations of five upper
      extremity muscles, and their spatial orientation tended to support an expected
      anatomic pattern. Muscle map locations and map areas showed trends across musical
      skill and hand dominance, as well. No subject experienced adverse effects during
      the study. TMS promises to be an effective tool for noninvasive cortical mapping.

PMID- 9263228
TI  - A mathematical model of the intracranial system including autoregulation.
AB  - Cerebral autoregulation plays an important role in the dynamic processes of
      intracranial physiology. This work develops a four-compartment, lumped-parameter
      model for the interactions of intracranial pressures, volumes, and flows as a
      test bed for examining the consistent inclusion of explicit autoregulation in
      mathematical models of the intracranial system. It is hypothesized that
      autoregulation of the blood supply from the arterioles to the capillary bed can
      be modeled by allowing the flow resistance at the interface of the artery and
      capillary compartments in the model to be a function of pressure rather than a
      constant. The functional dependence on pressure of this resistance parameter is
      not specified in advance, but emerges naturally from the assumed relationship
      between pressure differences and flows. Results show that a constant flow from
      the artery to the capillary compartment can be maintained by a flow resistance
      which is resistance which is directly proportional to the pressure difference
      between these two compartments. Oscillatory flow is reestablished in the model at
      the capillary-cerebrospinal fluid and capillary-venous interfaces.

PMID- 9263229
TI  - Distribution of myelin basic protein messages relative to the cytoskeleton.
AB  - In situ hybridization is performed on oligodendrocytes using oligo- nucleotide
      probes to determine the subcellular distribution of myelin basic protein (MBP)
      encoding messages which are associated with the cytoskeleton, relative to sub
      cellular distribution of all MBP-encoding messages in the cells.

PMID- 9263230
TI  - The effect of carbohydrates on affect.
AB  - This report reviews studies addressing the issue of the effect that carbohydrates
      have on affective behavior. The review begins with an overview of the physiologic
      and psychological mechanisms that have been proposed to explain a carbohydrate
      induced behavioral effect. Attention is then devoted to studies that have
      investigated the mood-altering effect of carbohydrates on normal individuals,
      depressed individuals, obese individuals, and individuals with seasonal affective
      disorder and premenstrual syndrome. Throughout the report it is apparent that
      carbohydrate consumption is relevant for individuals experiencing symptoms of
      emotional distress, particularly symptoms indicative of depression, and that the
      individuals with depressive symptoms show a preference for sweet simple
      carbohydrates. Enduring questions permeating the diet-behavior field are
      delineated and future research directions are suggested.

PMID- 9263231
TI  - Changes in nutritional status and patterns of morbidity among free-living elderly
      persons: a 10-year longitudinal study.
AB  - Nutritional intake appears to be an important factor contributing to aging. In
      the present study we describe changes in physical health related to nutritional
      intake among elderly persons in a 10-y longitudinal study. Among 304 healthy
      elderly participants (median age 72 y on entry into the study in 1980), 97
      (34.2%) are still in good health 10 y later in 1990, 74 (26.5%) have become frail
      or sick, 54 (19.1%) have died, and 57 (20.1%) have dropped out of the study.
      Women with lower or higher energy intakes (in 1980 and 1981) than the current
      Recommended Daily Allowance (RDA; between 25 and 30 kcal/kg) were more likely to
      become frail or sick or to die in 1990 than those with energy intake in the
      midrange (below RDA, odds ratio (OR) = 3.3, confidence interval (CI) = 1.2-8.6;
      above RDA, OR = 3.4, CI: 1.1-10.7). Moreover, women with protein intakes greater
      than the midrange of 0.8-1.2 g/kg of body weight (1.20-1.76 g/kg in 1980 and
      1981) tended to have fewer health problems over the next 10 y than those with
      protein intakes < 0.8 g/kg, suggesting that the mean protein requirement in
      elderly adults is greater than that established by the 1985 joint World Health
      Organization/ FAO/UNU Expert Committee. Moreover, a decrease in energy intake was
      greater in elderly persons who died or dropped out of the study because of
      illness.

PMID- 9263232
TI  - Percutaneous endoscopic gastrostomy: a long-term follow-up.
AB  - Percutaneous endoscopic gastrostomy (PEG) is the preferred method of long-term
      tube feeding, but only a few studies describe a long-term follow-up. The purpose
      of this study is to analyze the follow-up of PEG enteral feeding patients in the
      long term, and to report on the complication and survival rates. Between January
      1991 and June 1995, we studied 136 patients (49% cancer and 51% non-cancer
      patients; male = 68%, female = 32%) after PEG insertion. One hundred twenty-eight
      patients had a long-term follow-up of over 31 d. The mean duration of PEG feeding
      was 277 +/- 358 d (range 31-1590): 17% of patients returned to oral feeding, 34%
      continued enteral nutrition, and 49% died. Major complications occurred in 3% of
      the patients: 1 aspiration pneumonia, 1 subcutaneous abscess. 2 buried bumper
      syndrome. Minor complications arose in 14% of our cases: 8 tube blockages, 4 tube
      dislodgements, 6 site infections. For the whole group of 136 patients, survival
      probabilities after PEG insertion at 1, 6, 12, and 24 mo were 90.5%, 52%, 42%,
      and 35%, respectively. After 180 d, the difference in survival probabilities
      between cancer and non-cancer patients became significant (P < 0.02). Median
      survival probability was 64% for non-cancer and 39% for cancer patients, and this
      trend did not change over 2 y.

PMID- 9263233
TI  - Effect of sex and age on bone mass, body composition and fuel metabolism in
      humans.
AB  - The mechanism(s) governing the gain of upper-body fat and its relationship to the
      decrease in bone mass with age is still unclear. Therefore, four groups of
      subjects matched for weight, height, and body mass index (n = 119; 60 women, 59
      men), but differing in age (above and below 50 y) and sex were investigated using
      dual energy x-ray absorptiometry (DXA) to assess body composition (bone, lean,
      and fat mass as well as its distribution) and indirect calorimetry to determine
      resting fuel metabolism. Fat mass of trunk and arms (P < 0.01), but not legs,
      increased with advancing age in males, resulting in a continuous increase in the
      ratio of upper- to lower-body fat (r = 0.45, P < 0.001). In contrast, total fat
      mass remained stable in women, irrespective of menopause, but a redistribution of
      fat occurred with advancing age (r = 0.43, P < 0.001), resulting in a higher
      upper- to lower-body fat ratio (P < 0.05) in older than in younger women. Total
      lean soft-tissue mass of all segments of the body was greater in men than in
      women irrespective of age (P < 0.001), and lower in the older groups than in the
      younger ones irrespective of sex. In males, but not females, lean soft-tissue
      mass in arms and legs decreased (r = 0.57, P < 0.001), whereas the ratio of total
      fat to lean soft-tissue mass increased (r = 0.53, P < 0.001) with age. Bone
      mineral content correlated with total body fat in both groups of women and in
      young males (r > 0.5, P < 0.001), but not in older males. With advancing age, the
      proportion of lean soft-tissue mass occupied by total skeleton declined in women
      (n = 59, P < 0.001), but remained stable in males. Resting energy expenditure
      decreased with age in both sexes. Protein and carbohydrate oxidation were similar
      in all four groups of subjects. Total fat oxidation and fat oxidation per
      kilogram of lean soft-tissue mass decreased with age (r > 0.36, P < 0.01) in
      males, but not in females, whereas it increased with increasing fat mass in
      females (r > 0.32, P < 0.03), but not in males. In contrast, fat oxidation per
      kilogram of fat mass decreased with fat mass in males (r = 0.61, P < 0.001), but
      not in females. Our results suggest that aging affects body composition and fuel
      metabolism differently in each gender, leading to reduced fat oxidation and
      accumulation of upper-body fat with loss of striated muscle in men, and to an
      increased ratio of upper- to lower-body fat and bone loss in women, the latter
      depending on fat mass.

PMID- 9263234
TI  - Effects of diet supplementation with wheat bran on serum estrogen levels in the
      follicular and luteal phases of the menstrual cycle.
AB  - There is both epidemiologic and experimental support for the hypothesis that a
      high-fiber diet can reduce breast cancer risk; this may be due, at least in part,
      to a reduction in circulating estrogens. This study examined the effects of three
      levels of wheat bran supplementation (5, 10, and 20 g/d for 2 mo) on the major
      serum estrogens during both the luteal and follicular phases of the menstrual
      cycle. The 10- and 20-g supplements, which increased the total dietary fiber
      intakes to approximately 20 and 32 g/d, respectively, resulted in significant
      decreases in the luteal serum estrone (P < 0.05 and < 0.02, respectively). The
      serum estradiol was significantly reduced in the 10-g wheat bran group after 2 mo
      (P < 0.05); the 20-g supplemented group showed a significant decrease in
      estradiol at 1 mo (P < 0.02), but not at 2 mo. No changes occurred in the estrone
      sulfate concentrations. During the follicular phase, the 10-g wheat bran group
      exhibited a significant reduction in the serum estrone (P < 0.02). Only the serum
      estrone sulfate showed any reduction with the 20-g supplement, and this just
      failed to achieve significance (P = 0.07). Serum sex hormone-binding globulin
      levels were unaffected by wheat bran. When of long duration, these effects may be
      sufficient to favorably influence breast cancer risk in Western women.

PMID- 9263236
TI  - Stability of ranitidine and thiamine in parenteral nutrition solutions.
AB  - Our objectives were to ascertain the stability of thiamine HCl (3 mg/L) and
      ranitidine HCl (150 mg/L) at room and refrigeration temperatures in a central
      vein formula of parenteral nutrition (PN) solution (containing 6% amino acid, 25%
      carbohydrate, macro- and microminerals, and multivitamins) and to determine the
      effect of ranitidine on the stability of thiamine. Stability of thiamine and
      ranitidine in PN solutions was also compared with PN-salt solutions, which
      contained no amino acids or carbohydrates, to indirectly ascertain the impact of
      these macronutrients on the stability of these moieties. High-pressure liquid
      chromatography (HPLC) methods were developed to measure thiamine and ranitidine
      in the PN mixture. Stability studies were conducted in triplicate and each sample
      was assayed in duplicate using newly developed HPLC methods. Refrigeration
      provided stability for both ranitidine and thiamine for extended periods of time.
      At room temperature, ranitidine was also shown to be stable for about 188 h;
      there was, however, significant degradation of thiamine at 24 h with, and
      without, addition of ranitidine. The time required for 10% of thiamine to degrade
      was calculated to be 12.9 h for the PN mixture containing multivitamins and
      ranitidine; 11.1 h for the PN mixture containing multivitamins alone; and 33.4 h
      for the PN mixture containing only thiamine HCl. This work suggests that the
      concentration of thiamine in this central vein PN formula, with or without
      ranitidine, falls below the 90% acceptable stability within 24 h.

PMID- 9263235
TI  - Effects of growth hormone and insulin-like growth factor-1 on protein metabolism,
      gut morphology, and cell-mediated immunity in burned rats.
AB  - The effects of recombinant human growth hormone (GH) and insulin-like growth
      factor-1 (IGF-1) were investigated in burned rats. Sprague-Dawley rats were fed
      exclusively by total parenteral nutrition and were subjected to 20% third-degree
      scald burns. The rats were then divided into the following three groups: (1) the
      GH group received GH at a dose of 1 IU.kg-1.d-1 for 2d (n = 10); (2) the IGF
      group received IGF-1 at a dose of 4 mg.kg-1.d-1 for 2d (n = 19); and (3) the
      control group received saline (n = 17). Cumulative nitrogen balance increased
      significantly in the GH (P < 0.01) and IGF (P < 0.01) groups as compared with the
      control group. There were no differences in nitrogen balance between the GH and
      IGF groups. Blood glucose was decreased in the IGF group (P < 0.01) and increased
      in the GH group (P < 0.05) as compared with the control group. The intestinal
      villus height and wall thickness of the GH and IGF groups were significantly
      greater than those of the control group. Delayed-type hypersensitivity was
      enhanced in both the GH and the IGF groups as compared with the control group
      (both P < 0.01). Furthermore, the increase in the IGF group was significantly
      greater than that in the GH group (P < 0.05). It was concluded that both GH and
      IGF-1 improve protein metabolism and immune responsiveness, as well as promote
      proliferation of the intestinal mucosa.

PMID- 9263237
TI  - A bag carrier for continuous intravenous hyperalimentation.
AB  - We designed a new bag-carrier device system for continuous intravenous
      hyperalimentation. The patient carries it on his shoulder and can both walk up
      and down stairs and go out. The use of this device is simple and easy, and was
      found to increase the patient's opportunity to engage in physical activity.

PMID- 9263238
TI  - Venocutaneous fistula: a central venous catheter--associated complication.
AB  - Central venous catheter placement for parenteral feeding, whether short-term as
      in acute hospital care or long-term as in home total parenteral nutrition (TPN),
      is a well-established intervention in the patient who cannot eat. Access to the
      central venous system in the majority of the cases is gained by insertion of the
      catheter into either the subclavian or jugular vein. Associated with central
      venous catheters is the possible development of mechanical and septic
      complications, the incidence of which depends upon the skill, experience, and
      commitment of both the patient and the nutrition support team. A case report is
      presented in which a woman developed a venocutaneous fistula due to a chronic
      indwelling right internal jugular central catheter placed for long-term home
      nutritional support. The patient's medical history, management of her catheter,
      and proposed etiology for this problem are discussed, and complications of
      central access and TPN usage are addressed.

PMID- 9263239
TI  - New aspects on etiology, biochemistry, and therapy of portal systemic
      encephalopathy: a critical survey.
AB  - There is scientific agreement that portal systemic encephalopathy (PSE) is caused
      morphologically by portal systemic shunts and biochemically by constituents of
      the portal venous blood. Ammonium has a key role in the pathogenesis of PSE.
      Direct correlations with the degree of PSE have been established exclusively with
      glutamine, i.e. the terminal product of the peripheral detoxification of
      ammonium. In PSE, ammonium is probably responsible for damage to astrocytic and
      neuronal cells. Ammonium's toxic effect is due to the intracerebral glutamine
      synthesis. After several metabolic steps, which will be discussed in detail,
      brain cell damage is caused directly or indirectly (exitotoxically) by energy
      deficiency. Hyperammonemia and PSE are each well defined though different forms
      of disturbance. Therefore, ammonium is not the sole decisive factor in the
      pathogenesis of PSE. We performed a detailed and critical analysis of all studies
      on amino acid therapy of PSE, especially those that were randomized and
      controlled. This analysis revealed a close and direct correlation between
      qualitative and quantitative dosages of amino acids on one hand, and parallel
      improvements of amino acid imbalance (essentially associated with PSE) and degree
      of PSE on the other. A close and direct dose/efficacy correlation must be
      assumed. Disturbed plasmatic amino acid homeostasis and cerebral monoaminergic
      neurotransmission are probably important pathogenic factors of PSE. A fundamental
      cofactor in the efficacy of each adequate amino acid therapy might be a
      substantial decrease of endogenous ammonium production. Physiologic
      benzodiazepines may also have an important function in the pathogenesis of PSE:
      not so, however, the glutamate-ergic and GABA-ergic neurotransmission, which are
      disturbed principally in PSE. In close correlation to pathogenesis, established
      and proposed therapies of PSE are critically discussed.

PMID- 9263240
TI  - Victims of our own success.

PMID- 9263241
TI  - Aging and body composition.

PMID- 9263242
TI  - Long-term stability of body mass and physique.

PMID- 9263243
TI  - Glutamine homologues and derivatives: a limiting factor in current artificial
      nutrition?

PMID- 9263244
TI  - Peripheral parenteral nutrition and venous thrombophlebitis.

PMID- 9263245
TI  - Cereal foods and nutrition in ancient Egypt.

PMID- 9263246
TI  - Histamine and the neuroregulation of food intake.

PMID- 9263247
TI  - Weight as an outcome measure in hospital patients and role of catering services.

PMID- 9263248
TI  - Is hospital pharmacy practice at a crossroad?

PMID- 9263249
TI  - The dietitian's role in withholding and withdrawing nutritional support: special
      considerations for the older adult.

PMID- 9263250
TI  - The evolving health care market ... exploring alternatives.

PMID- 9263251
TI  - Workshop on cost-effectiveness in health and medicine.

PMID- 9263252
TI  - Influence of liver failure, ascites, and energy expenditure on the response to
      oral nutrition in alcoholic liver cirrhosis.
AB  - The influence of liver failure, ascites, and energy expenditure on the response
      to oral nutrition was assessed in a group of 55 alcoholic cirrhotic patients.
      Caloric intake, nutritional status, resting energy expenditure (REE), and Child
      Pugh score were evaluated before and after 1 mo of oral nutrition. Patients were
      severely malnourished, 73% had muscular midarm circumference (MMAC) below the 5th
      percentile of a reference population, 51% had triceps skinfold thickness below
      the 25th percentile. Eleven patients were in class A of Child, 19 in class B, and
      25 in class C. Twenty-six patients were nonascitic, whereas ascites was resolved
      in 10 ascitic patients by the end of the study and 19 patients had refractory
      ascites. Liver damage was more pronounced and did not improve during the study in
      patients with refractory ascites. Caloric intake was approximately 40 kcal/kg of
      body weight and was in the same range in the three groups according to Child
      classification. Fat mass (FM) increased, respectively, from 17.4% +/- 1.7% to
      19.5% +/- 1.4%, P < 0.01, in Child A patients; from 17.1% +/- 1.4% to 19.3% +/-
      1.4%, P < 0.001, in Child B patients; and from 17.6% +/- 1.5% to 18.8% +/- 1.5%,
      P < 0.05, in Child C patients. The increase in FM was comparable in the three
      groups, whereas MMAC and the creatinine/height ratio did not change
      significantly. FM was lower and did not increase in patients with refractory
      ascites. Child C patients were characterized by an increase in the rate of
      glucose oxidation (P < 0.02) and a decrease in the rate of lipid oxidation (P <
      0.05). High-density lipoprotein cholesterol and apolipoprotein (Apo) A1 were
      reliable indices of improvement of liver function in patients with severe liver
      failure, ApoA1 was also a marker of improvement of metabolic impairment. With
      respect to the measured REE/predicted REE ratio calculated according to Harris
      Benedict equation (r), 19 patients were considered hypermetabolic (r < 1.1), 30
      normometabolic (0.9 < r < 1.1), and 6 hypometabolic (r < 0.9). An increase in FM
      correlated with r (P < 0.01) and was more marked in hypermetabolic patients. In
      contrast to the other two groups, Child-Pugh score and nutritional status
      remained unchanged in the hypometabolic patients. These results show that severe
      liver failure did not preclude improvement of nutritional status provided caloric
      intake was high. In Child C patients, improvement of nutritional status
      paralleled improvement of liver function and normalization of oxidative
      metabolism. Refractory ascites had negative effects on changes in nutritional
      status and liver function. Despite adequate caloric intake to energy
      requirements, hypometabolism has a poor prognosis regarding both nutritional
      status and liver function.

PMID- 9263253
TI  - Clinical and laboratory evaluation of a closed enteral feeding system under
      cyclic feeding conditions: a microbial and cost evaluation.
AB  - Cyclic feeding schedules are now commonly used in conjunction with closed enteral
      feeding systems. Some manufacturers and clinicians have speculated that closed
      system cyclic feeding may promote formula contamination via retrograde movement
      of bacteria during the "no-flow" periods. Using both laboratory and clinical
      settings, our study evaluated whether retrograde bacterial movement under "no
      flow" conditions results in contamination of closed system feeding containers.
      The clinical phase was conducted with 57 closed system feeding containers used to
      feed nursing home residents. In both laboratory and clinical testing there was no
      evidence of container contamination at 36-48 h, nor was there evidence of
      retrograde movement of bacteria beyond the drip chamber. Formula waste and costs
      were also analyzed using several 24- or 36-h hang time scenarios. Provided the
      appropriate container size is used, potential cost savings between $67 to $135
      per patient per month may be achieved with the 36-h hang time scenarios.
      Retrograde movement of bacteria does not appear to be a source of closed system
      feeding container contamination in systems that incorporate a drip chamber. Using
      the appropriate size feeding container and systems with at least a 36-h hang time
      will result in significant cost savings.

PMID- 9263254
TI  - Body composition changes in patients with human immunodeficiency virus infection.
AB  - Malnutrition characterized by weight loss and often extreme wasting generally
      develops when patients progress from infection with human immunodeficiency virus
      (HIV) to AIDS. There is evidence that before the development of AIDS, HIV
      infected patients without weight loss show early signs of malnutrition, defined
      as an increase in the ratio of extracellular mass (ECM) to body cell mass (BCM).
      As part of a dietary intervention study, body composition measurement were
      obtained at baseline and after 6 wk in 18 patients with HIV infection and CD4
      counts between 140 and 740 cells/mm3. Only one patient had a prior weight loss
      (3.7 kg); patients gained 2 pounds after 3 wk of dietary supplementation of 500
      kcal daily. Bioelectrical impedance was used to measured body compartments. The
      average ECM/BCM ratio (0.77 +/- 0.13) was within the normal range (0.83 +/- 0.16)
      indicating the absence of malnutrition by this criterion. Most measurements of
      BCM (kg) approximated normal values, while several for BCM (kg) exceeded normal.
      BCM (kg) correlated poorly with the ECM/BCM ratio (r2 = 0.08; P = 0.11) in
      contrast to ECM (kg), which was well correlated (r2 = 0.82; P = 0.00). In
      addition, there was a significant correlation of body mass index (BMI) with the
      ECM/BCM ratio (r2 = 0.38; P = 0.00) and with ECM (r2 = 0.244; P = 0.003)
      indicating that overweight patients may be more likely to be considered
      malnourished than normal weight patients using this ratio. Without use of
      bioelectrical impedance, these subtle changes might be missed. Once significant
      weight loss has occurred coupled with decreases in BCM (kg), the ECM/BCM ratio
      may be more reflective of malnutrition. These conjectures will require
      prospective evaluation, but for now it seems reasonable to include bioelectrical
      impedance as a potentially useful tool in the evaluation of malnutrition in this
      population.

PMID- 9263255
TI  - Soybean protein lowers serum cholesterol levels in hamsters: effect of debittered
      undigested fraction.
AB  - The undigested fraction (UDF) of soybean protein exerts a marked
      hypocholesterolemic effect in relation to soybean protein (SOY) in rats. The
      present study was conducted to confirm whether UDF was effective in hamsters as
      in rats in combination with different fat sources, either perilla oil (PER) or
      safflower oil (SAF). Because the hamster, unlike the rat, disliked the bitter
      taste of UDF, the effect of debittering UDF also was studied. Cholesterol
      enriched (0.2%) diets containing 20% protein and 10% fat were fed to hamsters for
      4 wk. UDF was more hypocholesterolemic than soybean protein in hamsters
      regardless of the dietary fat source. The ratio of high-density lipoprotein to
      total cholesterol essentially remained unchanged. The debittered UDF, without
      influencing food intake and thereby weight gain, exerted a significant
      hypocholesterolemic effect comparable with UDF in relation to SOY accompanying
      stimulation of fecal neutral and acidic steroid excretion. The fatty acid
      composition of liver phospholipids was influenced by the type of the dietary
      protein, and both UDF seemed to interfere characteristically more than SOY with
      the desaturation systems between linoleic acid and arachidonic acid. Thus, the
      debittered UDF, similar to UDF, exerted a distinct influence on the various
      parameters of lipid metabolism in relation to SOY.

PMID- 9263257
TI  - Glutamine requirement of proliferating T lymphocytes.
AB  - Glutamine is required for lymphocyte proliferation but the site of glutamine
      action is not yet known. In this study, the effect of glutamine on key events
      that occur during lymphocyte activation [interleukin-2 (IL-2) production, IL-2
      use, IL-2 receptor expression, transferrin receptor expression] was investigated.
      Rat or mouse spleen lymphocytes were cultured in the presence of the T-cell
      mitogen concanavalin A (Con A) and various concentrations of glutamine. There was
      a trend (not significant) for the ratio of CD4+:CD8+ spleen lymphocytes to
      increase (from 1.9 to 2.6) as the concentration of glutamine in culture medium
      increased from 0 to 2 mmol/L. As the concentration of glutamine increased, there
      was an increase in the proportion of cells expressing the IL-2 receptor (from 30
      to 45%) and the transferrin receptor (from 34% to 55%). As the concentration of
      glutamine increased there was a 2.7-fold increase in the concentration of IL-2 in
      the culture medium. The IL-2 concentration was decreased when an IL-2 receptor
      blocking antibody was included in the culture medium; the IL-2 concentrations
      measured were taken to indicate the initial Con A-stimulated production of IL-2.
      In these conditions, the IL-2 concentration in the medium increased 39-fold as
      the glutamine concentration increased. The use of IL-2 by an IL-2-dependent cell
      line was dependent on the glutamine concentration in the culture medium. Thus,
      all four components of lymphocyte activation investigated (IL-2 production, IL-2
      use, IL-2 receptor expression, transferrin receptor expression) were dependent on
      the concentration of glutamine present in the culture medium. Thus, glutamine
      might provide an early signal in the lymphocyte activation process.

PMID- 9263256
TI  - Branched-chain transaminase and keto acid dehydrogenase activities in burned
      rats: evidence for a differential adaptation according to sex.
AB  - Female and male rats show differences in nitrogen metabolism after trauma, and
      the contribution of the branched-chain amino acid oxidizing pathway following
      thermal injury was evaluated. Female and male rats were subdivided into baseline,
      burned and unburned, pair-fed groups. Burned and pair-fed rats were sacrificed on
      days 1, 2, and 3 postburn, and branched-chain amino acid transaminase (BCTA),
      branched-chain alpha-keto acid dehydrogenase (BCKDH) activated and total, and
      succinate dehydrogenase (SDH) activities were measured in red and white muscle
      and in liver, BCTA was not measured in liver. Baseline and pair-fed groups had
      similar enzyme activities. Changes following thermal injury were: (1) elevated
      SDH in all tissues for both sexes; (2) increased BCTA activity in red and white
      muscles from male rats; and (3) increased percentage of activated BCKDH in red
      and white muscles on days 2 and 3 for male rats. All other activities were
      unchanged. These findings agree with previous post trauma differences in urinary
      nitrogen losses in female and male rats. The results show that the enzymes for
      oxidation of the branched-chain amino acids in males respond to injury while
      those do not in females.

PMID- 9263258
TI  - Effect of epidermal growth factor on glutamine metabolic enzymes in small
      intestine and skeletal muscle of parenterally fed rats.
AB  - Exogenous epidermal growth factor (EGF) markedly increases the in vivo uptake of
      glutamine by small intestine during total parenteral nutrition (TPN). Since
      glutamine is the major oxidative fuel for the small intestine and is synthesized
      mainly in skeletal muscle, we investigated whether EGF would induce changes in
      the activity of the enzymes that mediate glutamine degradation (glutaminase) and
      synthesis (glutamine synthetase) in the two tissues. Male Sprague Dawley rats
      were randomized into three groups: group I (chow) were fed rat chow and water and
      libitum, group II (TPN) received a standard formula of TPN, and group III (TPN
      EGF) received the same TPN as group II and injections of EGF (0.1 microgram/ gm
      body weight (bw)) subcutaneously twice daily. TPN was given for 2 wk; when EGF
      was administered along with TPN, the glutaminase activity of intestinal mucosa
      and the glutamine synthetase activity of skeletal muscle were increased,
      respectively, by 25% and 24% (P < 0.05, versus TPN group). These data suggest a
      mechanism whereby EGF enhances the intestinal utilization of glutamine by
      changing the activities of glutamine metabolic enzymes in the small intestine and
      skeletal muscle during TPN.

PMID- 9263259
TI  - Effects of garlic on atherosclerosis.
AB  - This review discusses the use of garlic and garlic preparations as agents for
      prevention and treatment of atherosclerosis and atherosclerosis-related diseases.
      Garlic indirectly effects atherosclerosis by reduction of hyperlipidemia,
      hypertension, and probably diabetes mellitus and prevents thrombus formation. In
      addition, in animal models, garlic causes direct antiatherogenic (preventive) and
      antiatherosclerotic (causing regression) effects at the level of artery wall.
      Garlic's direct effect on atherosclerosis may be explained by its capacity to
      reduce lipid content in arterial cells and to prevent intracellular lipid
      accumulation. This effect, in turn, is accompanied by other atherosclerotic
      manifestations, i.e., stimulation of cell proliferation and extracellular matrix
      synthesis. Clinical trials are currently being carried out to reveal the possible
      effect of garlic therapy on human atherosclerosis. Positive results of these
      trials may open a new era in the use of garlic for prevention and treatment of
      many atherosclerosis-related diseases.

PMID- 9263260
TI  - Calcium and osteoporosis.
AB  - Calcium is an essential nutrient that is involved in most metabolic processes and
      the phosphate salts of which provide mechanical rigidity to the bones and teeth,
      where 99% of the body's calcium resides. The calcium in the skeleton has the
      additional role of acting as a reserve supply of calcium to meet the body's
      metabolic needs in states of calcium deficiency. Calcium deficiency is easily
      induced because of the obligatory losses of calcium via the bowel, kidneys, and
      skin. In growing animals, it may impair growth, delay consolidation of the
      skeleton, and in certain circumstances give rise to rickets but the latter is
      more often due to deficiency of vitamin D. In adult animals, calcium deficiency
      causes mobilization of bone and leads sooner or later to osteoporosis, i.e., a
      reduction in the "amount of bone in the bone" or apparent bone density. The
      effects of calcium deficiency and oophorectomy (ovariectomy) are additive. In
      humans, osteoporosis is a common feature of aging. Loss of bone starts in women
      at the time of the menopause and in men at about age 55 and leads to an increase
      in fracture rates in both sexes. Individual fracture risk is inversely related to
      bone density, which in turn is determined by the density achieved at maturity
      (peak bone density) and the subsequent rate of bone loss. At issue is whether
      either or both of these variables is related to calcium intake. The calcium
      requirement of adults may be defined as the mean calcium intake needed to
      preserve calcium balance, i.e., to meet the significant obligatory losses of
      calcium through the gastrointestinal tract, kidneys, and skin. The calcium
      allowance is the higher intake recommended for a population to allow for
      individual variation in the requirement. The mean requirement defined in this
      way, calculated from balance studies, is about 20 mmol (800 mg) a day on Western
      diets, implying an allowance of 25 mmol (1000 mg) or more. Corresponding
      requirements and allowances have been calculated for pregnancy and lactation and
      for children and adolescents, taking into account the additional needs of the
      fetus, of milk production, and of growth. There is a rise in obligatory calcium
      excretion at menopause, which increases the theoretical calcium requirement in
      postmenopausal women to about 25 mmol (1000 mg) and implies an allowance of
      perhaps 30 mmol (1200 mg) or even more if calcium absorption declines at the same
      time. At issue here, however, is whether menopausal changes in calcium metabolism
      are the cause or the result of postmenopausal bone loss. The first interpretation
      relies on evidence of a positive action of estrogen on the gastrointestinal
      absorption and renal tubular reabsorption of calcium; the latter interpretation
      relies on evidence of a direct inhibitory effect of estrogen on bone resorption.
      The calcium model for postmenopausal bone loss tends to be supported by the
      effect of calcium therapy. An analysis of the 20 major calcium trials in
      postmenopausal women reported in the last 20 years yielded a mean rate of bone
      loss of 1.00% per annum (p.a.) in the controls and 0.014% p.a. (NS) in the
      treated subjects (P < 0.001). However, trials in which calcium and estrogen have
      been directly compared have shown that the latter is generally more effective
      than calcium in that it produces a small, but often significant bone gain. This
      superiority of estrogen over calcium could be due to the former's dual action on
      calcium absorption and excretion or to a direct action of estrogen on bone
      itself. In older women, the importance of calcium intake is overshadowed by the
      strong association between vitamin D insufficiency and hip fracture. Whether this
      insufficiency arises primarily from lack of exposure to sunlight or to a
      progressive failure to activate the vitamin D precursor in the skin or both is
      uncertain but it is compounded by a general decline in dietary vitamin D intake
      with age. The biological effect is probably an impairment of calcium absorption
      and c

PMID- 9263261
TI  - On the impact of the metabolic state in cirrhotic patients.

PMID- 9263262
TI  - Nutrition: a whole-organism science.

PMID- 9263263
TI  - Energy metabolism in brain dead organ donors.

PMID- 9263264
TI  - The evolutionary imperative and the origin of the prion pathogen.

PMID- 9263265
TI  - The link between bracken fern and stomach cancer: milk.

PMID- 9263266
TI  - L-glutamate and N-methyl-D-aspartate receptors: learning, growth, and death in
      the mammalian brain.

PMID- 9263267
TI  - Beta-carotene supplementation and cancer prevention.

PMID- 9263268
TI  - Satisfaction data as quality measures for long-term care residents.

PMID- 9263269
TI  - The patient as a valuable source of outcomes and quality information.

PMID- 9263270
TI  - Dietary and dining expectations of residents of long-term care facilities.

PMID- 9263271
TI  - Measuring consumer satisfaction in nursing home residents.

PMID- 9263272
TI  - Zinc and the common cold: are we close to a cure?

PMID- 9263273
TI  - Working the margins.

PMID- 9263274
TI  - Credentialing: achievement or alphabet soup?

PMID- 9263275
TI  - Assessment of nutritional status via anthropometry.

PMID- 9263276
TI  - The Third Oxford Glutamine Workshop, 20 March 1996.

PMID- 9263277
TI  - The proposed role of glutamine in some cells of the immune system and speculative
      consequences for the whole animal.
AB  - The activity of glutaminase is high in lymphoid organs, lymphocytes and
      macrophages and increases in the popliteal lymph node in response to an
      immunological challenge. Consistent with this high activity, glutamine is
      utilised at a high rate by resting lymphocytes and macrophages in culture.
      Mitogenic stimulation of lymphocytes increases both glutaminase activity and the
      rate of glutamine utilisation. The major products of glutamine utilisation by
      lymphocytes and macrophages in culture are glutamate, aspartate, lactate and
      ammonia; < 25% of the glutamine used is completely oxidised. It is suggested that
      the high rate of glutamine utilisation by cells of the immune system serves to
      maintain a high intracellular concentration of intermediates of biosynthetic
      pathways such that optimal rates of DNA, RNA and protein synthesis can be
      maintained. In the absence of glutamine, lymphocytes do not proliferate in vitro;
      proliferation increases greatly as the glutamine concentration increases. The
      synthesis of interleukin-2 by lymphocytes and of interleukin-1 by macrophages is
      glutamine-dependent. Macrophage-mediated phagocytosis is influenced by glutamine
      availability. Glutamine is synthesized in skeletal muscle. Skeletal muscle and
      plasma glutamine levels are lowered by sepsis, injury, burns, surgery and
      endurance exercise and in the overtrained athlete. These observations indicate
      that a significant depletion of the skeletal muscle glutamine pool is
      characteristic of trauma and it has been suggested that the lowered plasma
      glutamine concentration contributes, at least in part, to the immunosuppression
      which accompanies such situations. Beneficial effects of the provision of
      glutamine or its precursors have been reported in patients following surgery,
      radiation treatment or bone marrow transplantation or suffering from injury,
      sepsis or burns.

PMID- 9263278
TI  - Glutamine dipeptides in clinical nutrition.
AB  - Glutamine is a conditional indispensable amino acid during stress. However,
      limited solubility and instability of glutamine prevent its addition to presently
      available nutritional preparations. To overcome these drawbacks, we propose the
      dipeptide concept by which stable and highly soluble synthetic glutamine
      containing dipeptides are used. The synthetic dipeptides fulfill all
      chemical/physical properties to be considered as parenteral substrates. Numerous
      experimental studies show rapid clearance of parenteral supplied glutamine
      containing dipeptides without accumulation in tissues; the loss via the urine
      being inconsequential. Differences related to the dipeptide structure are not
      observed. There is overwhelming evidence existent that a nutritional support with
      supplemental glutamine dipeptide positively influences nitrogen excretion, immune
      status, gut integrity, morbidity, rehabilitation and outcome. Consequently,
      omission of glutamine from conventional TPN and its subsequent administration
      should be considered as a replacement of a deficiency rather than a
      supplementation. It might thus be conceivable that the beneficial effects
      observed with glutamine nutrition are simply a correction of disadvantages
      produced by an inadequacy of conventional amino acid solutions. The availability
      of stable glutamine containing preparations will certainly facilitate an adequate
      amino acid nutrition in routine clinical setting during episodes of stress and
      malnutrition.

PMID- 9263279
TI  - The effects of oral glutamine supplementation on athletes after prolonged,
      exhaustive exercise.
AB  - Athletes undergoing intense, prolonged training or participating in endurance
      races suffer an increased risk of infection due to apparent immunosuppression.
      Glutamine is an important fuel for some cells of the immune system and may have
      specific immunostimulatory effects. The plasma glutamine concentration is lower
      after prolonged, exhaustive exercise: this may contribute to impairment of the
      immune system at a time when the athlete may be exposed to opportunistic
      infections. The effects of feeding glutamine was investigated both at rest in
      sedentary controls and after exhaustive exercise in middle-distance, marathon and
      ultra-marathon runners, and elite rowers, in training and competition.
      Questionnaires established the incidence of infection for 7 d after exercise:
      infection levels were highest in marathon and ultra-marathon runners, and in
      elite male rowers after intensive training. Plasma glutamine levels were
      decreased by approximately 20% 1 h after marathon running. A marked increase in
      numbers of white blood cells occurred immediately after exhaustive exercise,
      followed by a decrease in the numbers of lymphocytes. The provision of oral
      glutamine after exercise appeared to have a beneficial effect on the level of
      subsequent infections. In addition, the ratio of T-helper/T-suppressor cells
      appeared to be increased in samples from those who received glutamine, compared
      with placebo.

PMID- 9263280
TI  - The use of glutamine in the treatment of gastrointestinal disorders in man.
AB  - The human gastrointestinal tract (GIT) is a major site of glutamine utilisation
      accounting for more than half of the net splanchnic utilisation (approximately 15
      g/day) of glutamine obtained from the systemic circulation. Dietary glutamine
      (approximately 5 g/day) is less important than circulating glutamine, especially
      in disease conditions associated with substantial reduction in food intake.
      Glutamine has multiple effects on the structure and function of the GIT, and
      effects in improving morbidity and mortality in animal models of GIT damage has
      led to a series of studies in man, which have produced variable results.
      Glutamine administration to treat mucositis of the upper GIT (mouth, oesophagus)
      due to cytotoxic drug therapy, has produced no evidence of benefit. Early studies
      suggested improved healing, as do recent studies of small intestinal mucositis
      resulting from chemotherapy. Investigations in colitis are lacking although in
      experimental rat models of colitis no benefit has been reported. Multiple
      explanations can be put forward to explain the overall results, including the GIT
      distribution of enzymes involved in glutamine metabolism. Apart from the lower
      stomach in man (upper stomach in the rat) there is very little weak activity of
      glutamine synthetase, suggesting that the gut derives glutamine formed in other
      tissues and from the diet. The activity of glutaminase, which is key flux
      generating enzyme involved in glutaminolysis is very weak in mucosa with
      stratified squamous epithelium (oesophagus), where intermediate in the same
      intestine, and highest in the small intestinal mucosa which accounts for about
      80% of the total glutaminase in the entire human GIT mucosa.

PMID- 9263281
TI  - Glutamine supplementation in cancer patients receiving chemotherapy: a double
      blind randomized study.
AB  - The purpose of this study was to evaluate the efficacy of glutamine in preventing
      doxifluridine-induced diarrhea and the potential impact of glutamine on the tumor
      growth. We investigated 65 patients with advanced breast cancer receiving
      doxifluridine in a double-blind randomized fashion: 33 patients took glutamine
      (30 g/d, divided in 3 doses of 10 g each) for 8 consecutive days (5-12h) during
      each interval between chemotherapy, which was administered from day 1 to 4.
      Thirty-two patients took an equal dose of placebo (maltodextrine). The incidence
      of diarrhea was registered after each cycle of chemotherapy and severity was
      scored by the National Cancer Institute (NCI), Bethesda, Maryland,
      classification. The tumor response was evaluated by the World Health Organization
      (WHO) criteria. A total of 278 and 259 cycles (median 10 cycles), respectively,
      were delivered in glutamine and placebo groups. There were 34 and 32 episodes of
      diarrhea in glutamine and placebo groups, with no statistical difference overall,
      in the severity and duration of tumor growth, there was no difference in the
      response rate (21% and 28% of complete or partial response, respectively), in
      median time to response (2 mo), or in median duration of response. In conclusion,
      glutamine did not prevent the occurrence of the doxifluridine-induced diarrhea
      and did not have any impact on tumor response to chemotherapy.

PMID- 9263282
TI  - Outcome of critically ill patients after supplementation with glutamine.
AB  - Glutamine has many important metabolic roles that may protect or promote tissue
      integrity and enhance the immune system. The normal abundance of glutamine has
      meant that it has not been considered necessary to include glutamine in
      traditional parenteral feeds. However, low plasma and tissue levels of glutamine
      (Gln) in the critically ill suggest that demand may exceed endogenous supply. A
      relative deficiency of glutamine in such patients could compromise recovery,
      result in prolonged illness, and an increase in late mortality. The few percent
      of the most critically ill intensive care patients who are unable to tolerate
      enteral nutrition are especially at risk since they have increased demands for
      glutamine yet lack an exogenous supply. Such patients undergo considerable
      skeletal muscle wasting compromising glutamine supply further. In a prospective,
      randomised double blind clinical study of 84 patients with a high mortality due
      to multiple organ failure requiring parenteral feeding a significant improvement
      in six-month survival was observed in the group supplemented with glutamine 24/42
      versus isonitrogenous, isoenergetic control 14/42, P = 0.049.

PMID- 9263283
TI  - Elemental diets in the repair of small intestinal damage.
AB  - We have investigated the possible benefits of elemental diets, especially a diet
      supplemented with L-glutamine, on maintenance of intestinal absorptive function
      in rat small intestine damaged by 5-fluorouracil. Although a standard rat diet
      sustained better body growth in control rats, each of the elemental diets and the
      diet containing intact casein in place of hydrolyzed casein was beneficial in
      promoting less body weight loss during the 3 d after 5-fluorouracil injection.
      The same significant benefit was seen in absorptive activity measured in small
      intestine in vitro 3 d after the cytotoxic injury. Glutamine supplementation,
      however, did not confer any significant advantages, although it did cause
      significant elevation of muscle glutamine pools. This elevation was substantially
      less than the corresponding increase in muscle glycine content after dietary
      supplementation with glycine.

PMID- 9263284
TI  - Prescription drug budgets for physicians.

PMID- 9263285
TI  - The Bridgeport Hospital experience with autologous transfusion in orthopedic
      surgery.
AB  - The transfusion records of 341 orthopedic patients who donated blood
      preoperatively in the years 1992 and 1993 were audited to review the transfusion
      practices associated with the surgical procedures. The study sample underwent 182
      total knee (TKA), 123 total hip (THA) arthroplasties, and 33 laminectomies with
      fusion (LAM) and 3 without. Data used were age, gender, predonation hemoglobin
      concentration (Hbd), initial (Hbi) and final (Hbf) hemoglobin concentration,
      surgical procedure, surgical blood order (SBO), and estimated blood loss (EBL).
      We analyzed for means and associations and differences between covariates. The
      means of EBL (mL), transfused units, donated units, Hbi, (g/dL), Hbd, and Hbf
      (g/dL) for the most common procedures were: TKA--272, 1.1, 2.1, 10.4, 13.9, and
      10.1; THA--951, 2.3, 2.4, 9.4, 13.8, and 9.9; and LAM--589, 1.5, 2.2, 12.0, 14.6,
      and 11.2. Phlebotomies for procedures with minimal blood loss, as for total knee
      arthroplasties, result in wastage. Autodonation under such circumstances takes
      patients to an unnecessary low hemoglobin concentration prior to either
      retransfusing the blood taken or discarding part of it. The number of
      preoperative autologous units donated can be reduced if predonation hemoglobin
      concentration is > 15 g/dL and expected blood loss is not > 2 g.

PMID- 9263286
TI  - Thiazide-induced hyponatremia in the postoperative total joint replacement
      patient.
AB  - The thiazide diuretic is a common medication in the elderly population for the
      treatment of hypertension. These same patients are the largest population for
      surgical intervention for joint arthroplasty. Postoperative management of these
      patients has shown to be complicated by hyponatremia associated with the use of
      thiazide diuretics. This study evaluates a consecutive series of 408 patients
      undergoing elective joint arthroplasty. An association was found with the use of
      thiazide diuretics in the preoperative period and the development of
      postoperative hyponatremia. The study is presented, along with a relevant review
      of the literature and suggestions for the orthopedic staff to limit the risk of
      hypoantremia and prolonged hospitalization in an otherwise stable postoperative
      course.

PMID- 9263287
TI  - Cervical disk disease and the keyhole foraminotomy: proven efficacy at extended
      long-term follow up.
AB  - Eighty-four consecutive patients with posterolateral cervical disk herniation
      treated by keyhole foraminotomy between 1980 and 1987 were reviewed. Radicular
      pain was the most common presenting complaint. Weakness was present in 59
      patients. Sixty patients were available for long-term follow up, averaging 6.1
      years. Fifty-six patients' results were graded as excellent. Three patients had
      good results and one fair result was noted. There were no poor results.
      Preoperative pain symptoms were relieved in all patients. There were no
      significant complications. The posterolateral keyhole foraminotomy is an
      efficient means of decompressing lateral soft disk herniations, without the risk
      of an anterior approach or iliac crest bone harvest. Careful patient selection
      and use of an operative microscope are essential in obtaining consistent,
      excellent results.

PMID- 9263288
TI  - Mechanical evaluation of a soft cast material.
AB  - In this study, the structural and material properties of a new semi-rigid
      material, Scotchcast SoftCast (SCS), were compared to the properties of two rigid
      materials, plaster of paris (POP) and Scotchcast Plus (SCP). Cylinders and flat
      beams made from 4, 6, 8, and 10 layers of each casting material were tested in
      three-point bending and diametrical compression. Initial stiffness and yield
      force values of SCS casts were significantly lower than for casts of SCP and POP
      made of the same number of layers. Casts made from SCS may be indicated for non
      rigid applications, but not where rigid immobilization is required.

PMID- 9263289
TI  - Placement of screws in the uncemented acetabulum: anatomic analysis of the danger
      zone.
AB  - Six cadavers were used to define the projection of the external iliac artery on
      the inner table of the acetabulum, and to quantitatively determine bony
      dimensions of the danger zone with regard to screw placement. The results showed
      that the majority of projections of the external iliac arteries were located on
      the superior portion of the posterosuperior quadrant and extended to the mid
      superior portion of the anterosuperior quadrant (danger zone). The inferior
      portion of the danger zone was relatively far from the external iliac artery. The
      greatest depths of bone were found in the inferior portion of the danger zone,
      and the depths of bone in the middle and superior portion of the danger zone were
      relatively thinner. This anatomic study showed that the real danger zone was
      found in the middle and superior portions of the anterosuperior quadrant of the
      acetabulum. The inferior portion of the anterosuperior quadrant was relatively
      safer. This area may be considered if transacetabular screw replacement in the
      anterosuperior quadrant is required.

PMID- 9263291
TI  - Acute traumatic vertical axis rotational dislocation of the patella.

PMID- 9263290
TI  - Treatment of considerations in patients with compartment syndrome and an
      inherited bleeding disorder.
AB  - In addition to consultation with an experienced hematologist, the following are
      recommendations regarding compartment syndrome in a patient with an inherited
      bleeding disorder. Von Willebrand's Disease. Humate-P (rich in von Willebrand
      factor) is the replacement therapy of choice for surgical procedures in patients
      with von Willebrand's disease. In general, in the perioperative period, factor
      VIII levels between 50% and 100% are ideal with a gradual tapering to maintain
      levels at 50% for approximately 2 weeks. Adjuncts to therapy are DDAVP and EACA.
      Hemophilia A. During the initial evaluation and with measurement of compartment
      pressures, factor VIII replacement to levels in the range of 40% to 60% of normal
      is appropriate replacement therapy. For fasciotomy, however, factor VIII levels
      greater than 50% to 100% are required. In patients who have developed antibodies
      to factor VIII, a number of options are available. With low titers of factor VIII
      inhibitor, higher doses of factor VIII may be successful in overriding the
      inhibitor. In patients with higher titers of inhibitor, activated factor VII or
      porcine factor VIII is recommended. Hemophilia B. Highly purified factor IX
      replacement aimed at keeping factor levels between 50% and 100% in the
      perioperative period, followed by maintenance at 50% for approximately 2 weeks,
      is optimal management. Treatment Algorithm: The Figure outlines an algorithm to
      aid in the diagnosis and treatment of compartment syndrome in the patient with an
      inherited bleeding disorder. In a suspected case of compartment syndrome due to a
      soft-tissue hemorrhage or injury, factor replacement as outlined above should be
      initiated. Unequivocal clinical findings in the normal patient usually would be
      an indication to proceed to fasciotomy without obtaining compartment pressures.
      In the patient with an inherited bleeding disorder, however, factor replacement
      and subsequent normalization of the clotting cascade may help lowe compartment
      pressures. Therefore, we advocate obtaining initial pressures even with clinical
      findings of an acute compartment syndrome. At our institution, we advocate using
      an automated handheld pressure monitor (Stryker, Ontario, Canada) or the needle
      injection technique as described by Whitesides et al. In interpreting the
      obtained pressures, we choose to use the guidelines as described by Heppenstall
      et al. Briefly, Heppenstall et al determined that the pressure threshold at which
      cellular damage occurred was related more closely to the difference between the
      mean arterial blood pressure and compartment pressure than with the absolute
      compartment pressure alone; this measurement is called delta P. If delta P is >
      30 mm Hg, then one should continue factor replacements and perform serial
      clinical and pressure examinations. Pressures should be taken every hour for 2
      hours total. If the patient worsens in either respect, then the physician should
      enter the other limb of the algorithm for delta P < 30 mm Hg. For the patient
      with a delta P < 30 mm Hg, the amount of time since onset of symptoms must be
      considered. Since the patient may improve with adequate factor replacement, a
      delta P < 30 mm Hg mercury does not dictate automatic fasciotomy. An adequate
      time trial of replacement therapy may be attempted. In patients whose pressures
      do not begin normalizing, we advocate proceeding to fasciotomy. Patients who
      begin to normalize pressures during a 2-hour trial can be followed with serial
      clinical and pressure examinations. Any worsening in either scenario is an
      indication for fasciotomy; otherwise, observation and factor replacement may be
      continued. After initial decompression, staples may be placed in both wound edges
      with an elastic vascular loop woven between the two edges in a "shoelace"
      pattern. Then while waiting for closure, the loops can be gradually tightened at
      the bedside. Definitive closure should be attempted around the fifth
      postoperative day. All closure techniques should be pre

PMID- 9263292
TI  - Bilateral, asynchronous, apophyseal fractures in the pelvis and proximal femur.

PMID- 9263293
TI  - Nonunited carpal scaphoid fracture in a child: treatment with pulsed
      electromagnetic field stimulation.

PMID- 9263294
TI  - Intraosseous epidermoid cyst in a metacarpal mimicking malignancy.

PMID- 9263296
TI  - More on risk management.

PMID- 9263295
TI  - Radiologic case study. Skewfoot.

PMID- 9263297
TI  - More on sports medicine.

PMID- 9263298
TI  - "This doesn't hurt, does it Johnny?".

PMID- 9263299
TI  - The preoperative evaluation of the pediatric patient.

PMID- 9263301
TI  - Preparation and intraoperative management of the pediatric patient.

PMID- 9263300
TI  - Emergence and recovery from anesthesia for pediatrics patients in the post
      anesthesia care unit.

PMID- 9263302
TI  - The use of neuromuscular-blocking agents in children.

PMID- 9263303
TI  - Postoperative pain management.
AB  - Recent evidence has documented the deleterious physiologic effects of pain and
      the beneficial results of effective postoperative analgesia. As outlined in this
      article, a three-step approach is recommended depending on the severity of pain.
      The three-step approach utilizes a combination of NSAIDs, oral or intravenous
      opioids. In addition to selecting a particular opioid to use, the practitioner
      must also consider the route of administration and the mode of administration.
      All three choices may significantly impact on the efficacy of analgesia. While we
      continue to use primarily intravenous opioids to treat moderate and severe pain
      in the hospital setting, future formulations and developments may allow for the
      increased use of non-parenteral routes.

PMID- 9263304
TI  - Sun Smart Day: a pilot program for photoprotection education.
AB  - Excessive exposure to the sun's ultraviolet radiation (UVR) contributes to the
      etiology of melanoma and nonmelanoma skin cancers. Many behaviors that increase
      lifetime risk of skin cancer--sun exposure, sunburn, and lack of sun protection-
      occur early in childhood. A 1-day school-based skin cancer prevention effort--Sun
      Smart Day--was implemented and evaluated in three elementary schools to improve
      fourth-graders' knowledge, attitudes, and behaviors related to skin cancer
      prevention. A classroom-based skin cancer prevention lesson was compared to an
      interactive sun safety fair was vehicles for promoting comprehensive
      photoprotection. Sun Smart Day interventions had their greatest impact on fourth
      graders' awareness and knowledge of skin cancer and children's increased
      knowledge persisted through the summer break. While both the classroom curriculum
      and the health fair boosted awareness and knowledge of sun safety among fourth
      graders, the classroom curriculum demonstrated a slight immediate advantage over
      the health fair on these outcomes. Also the curriculum was less difficult to
      implement, but the health fair was more engaging. A Sun Smart Day program may be
      an important first step in increasing public awareness and understanding of skin
      cancer and its prevention.

PMID- 9263305
TI  - Misdiagnosis, treatments, and outcomes in the immunobullous diseases in children.
AB  - As a group, the immunobullous diseases are very uncommon in childhood. We
      analyzed all cases of immunobullous diseases in individuals under age 18 years
      which we had evaluated at the University of Colorado and examined their age of
      onset, diagnostic difficulties, treatments, and outcomes. This was considered to
      be a representative North American population within a single referral area which
      contained a diverse ethnic population mixture. Further, we believe this study to
      be uniquely uniform in that all the patients were examined by us using the same
      diagnostic strategy and the immunofluorescent (IF) diagnostic tests were
      performed by the same individual (J.C. Huff) using uniform diagnostic criteria
      and consistent IF techniques.

PMID- 9263306
TI  - Gianotti-Crosti syndrome associated with Epstein-Barr virus infection.
AB  - Gianotti-Crosti syndrome (GCS) is a distinct exanthematic, acrolocated eruption
      of childhood caused by a variety of infectious agents. Historically hepatitis B
      antigen positive (HBsAG+) papular acrodermatitis of childhood and HBsAg negative
      (HBsAg-) papulovesicular acrolocated syndrome have been distinguished. Here we
      characterize the spectrum of associated infectious agents in seven patients with
      confirmed GCS seen in our departments in the years 1994-1995. Where available,
      stored frozen serum samples were reanalyzed for antiviral antibodies. The mean
      age of the two girls and five boys was 22.5 months with a range of 8 to 53
      months. None of the patients was HBsAG+. Four patients showed serologic evidence
      of an acute infection and one patient of a recent Epstein-Barr virus (EBV)
      infection. In two additional children vaccination preceded the appearance of GCS.
      In these two patients serologic investigations revealed no evidence of recent
      infection with most common viruses. Our results underline the role of viral
      infections other than hepatitis B in the etiology of GCS. EBV infection was the
      most commonly associated viral disease in our population. We agree with other
      authors that we should avoid using the terms papular acrodermatitis of childhood
      and papulovesicular acrolocated syndrome in describing HBsAg+ and HBsAg- forms of
      GCS.

PMID- 9263307
TI  - Phylloid pigmentary pattern with mosaic trisomy 13.
AB  - In most patients with hypomelanosis of Ito, the hypopigmentation is characterized
      by narrow bands following the lines of Blaschko. We report a 13-year-old severely
      retarded girl with leaf-shaped patches of hypopigmentation on the back together
      with short stature, scoliosis, facial dysmorphism, and asymmetrical leg length.
      The cytogenetic examination of both lymphocytes and fibroblasts demonstrated a
      mosaicism of 46,XX/47,XX+13. This result was confirmed by in situ hybridization
      using a chromosome 13-specific library in interphase cells. The pigmentary
      disturbance of our patient was similar to the phylloid pattern (type 3) of the
      classification of pigmentary patterns postulated by Happle. This type has been
      described in four patients so far, along with additional anomalies and a
      chromosomal mosaisicm in two patients.

PMID- 9263308
TI  - Cutaneous leiomyosarcoma in a child.
AB  - Superficial leiomyosarcomas are infrequent tumors that are very rare in
      childhood. We report on a 12-year-old white boy with a cutaneous leiomyosarcoma
      of his left groin. Immunohistochemical study revealed positive immunostaining
      with antibodies to vimentin, desmin, and smooth muscle actin. The tumor was
      removed with wide surgical margins.

PMID- 9263309
TI  - Urticaria pigmentosa presenting with massive peripheral eosinophilia.
AB  - A 5-month-old Hispanic boy had a diffuse eruption and massive peripheral
      eosinophilia. Mastocytosis was diagnosed by skin biopsy and Giemsa stain. Other
      causes of eosinophilia were ruled out by bone marrow examination and negative
      cultures. The patient's course improved with antihistamines and the removal of
      mast cell degranulating agents. Clinicians need to be aware that mastocytosis
      should be considered in the differential diagnosis of eosinophilia.

PMID- 9263310
TI  - Multiple leiomyomata presenting in a child.
AB  - We report a 2-year-old boy with a plaque on the upper arm composed of multiple 2-
      to 3-mm leiomyomata which developed at the age of 3 months and have been
      unchanged since. Immunohistologically there was positive staining for the muscle
      intermediate filament desmin. We discuss the unusual clinical presentation and
      possible prognosis.

PMID- 9263311
TI  - Mycobacterium fortuitum infection occurring after a punch biopsy procedure.
AB  - Mycobacterium fortuitum is a rapidly growing atypical mycobacterium frequently
      reported as a postsurgical wound complication from a major surgical procedure. We
      present a unique case of M. fortuitum infection occurring in a 4-year-old boy
      after a minor punch biopsy surgical procedure. As far as we know there has been
      no published case of M. fortuitum occurring after a punch biopsy procedure.

PMID- 9263312
TI  - Simultaneous occurrence of lichen striatus in siblings.
AB  - Lichen striatus (LS) is a self-limiting linear papular dermatosis of unknown
      etiology seen mostly in children. We report LS occurring in two pairs of
      siblings: two sisters who had LS at an interval of 6 months and a brother and
      sister who had the dermatosis contemporaneously after an episode of flulike
      fever. In all four patients family history was positive for atopy. LS is
      frequently associated with atopic diseases. The abnormal immune status of
      patients with atopy may be a predisposing factor in the induction of LS. In our
      patients the simultaneous occurrence of LS in siblings after a flulike fever
      appears to corroborate the hypothesis that a viral infection is a possible
      candidate, as other authors have proposed. The rarity of familial cases of LS is,
      in our opinion, due to the exceptional confluence of difference sporadic events
      (atopy, viral infection caught at a specific period of life such as childhood,
      and a genetic predisposition) simultaneously present in the same patient.

PMID- 9263313
TI  - Neurofibromatosis and reticulate acropigmentation of Dohi: a case report.
AB  - A 13-year-old boy had progressive pigmentary changes affecting his limbs which
      began when he was 9 months of age. He also had a history of cafe au lait macules
      on his trunk since birth which were becoming more numerous. The diagnosis of
      reticulate acropigmentation of Dohi (dyschromatosis symmetrica hereditaria) and
      neurofibromatosis type 1 (NF-1) was made on the basis of the clinical features.
      To our knowledge, this is the first report of these two conditions occurring in
      the same patient.

PMID- 9263314
TI  - Pulmonary hemorrhage: an often fatal complication of Henoch-Schoenlein purpura.
AB  - Two patients with Henoch-Schoenlein purpura developed pulmonary hemorrhage. One
      patient survived after treatment with intravenous methylprednisolone and
      cyclophosphamide; the other patient died from cardiopulmonary arrest before
      therapy could be initiated. Although rare, pulmonary complications of Henoch
      Schoenlein purpura can lead to rapid demise unless immediate supportive treatment
      is initiated.

PMID- 9263315
TI  - Linear IgA disease with clinical and immunopathological features of epidermolysis
      bullosa acquisita.
AB  - A 10-year-old boy had a 3-month history of urticarial plaques and vesicles.
      Histologic and immunofluorescence testing confirmed the diagnosis of linear IgA
      disease. Immunoelectron microscopy revealed IgA deposits in the sublamina densa
      area similar to those seen in epidermolysis bullosa acquisita. Milia developed
      after resolution of the lesions, similar to lesions of epidermolysis bullosa
      acquisita.

PMID- 9263316
TI  - Herlitz junctional epidermolysis bullosa: a case report and review of current
      diagnostic methods.
AB  - We report an infant with Herlitz junctional epidermolysis bullosa (JEB)
      presenting at birth with erosions on the scalp, thigh and periumbilical area in
      addition to nail abnormalities. Ultrastructural studies demonstrated a split
      through the lamina lucida with poorly formed hemidesmosomes and no clearly
      defined subbasal dense plates. Indirect immunofluorescence staining with
      antibodies GB3 (antilaminin 5) and 19-DEJ-1 (antiuncein) was totally absent.
      These findings, in combination with the clinical picture, favor a diagnosis of
      Herlitz JEB. Immunohistochemistry findings greatly facilitated an accurate
      diagnosis, which is essential in view of the poor prognosis for patients with
      this form of junctional epidermolysis bullosa.

PMID- 9263317
TI  - Congenital Wells syndrome.
AB  - We describe a girl with eosinophilic cellulitis (Wells syndrome) in whom the
      disease appeared immediately after birth with subcutaneous nodules on the scalp
      and trunk, followed by the characteristic skin swelling and erythema at the age
      of 6 months. The lesions disappeared after a few weeks, but recurred several
      times. The mother had consumed large quantities of medications during the
      pregnancy, including iron, vitamins, and "natural remedies." Based on time of
      onset, this may be regarded as a unique case of congenital Wells syndrome. Its
      relation to the medications taken by the mother remains speculative. Subcutaneous
      nodules may be the presenting sign of Wells syndrome in children.

PMID- 9263318
TI  - Diffuse whitening of the oral mucosa in a child.
AB  - We report a healthy 16-year-old Caucasian boy, who consulted us for white,
      asymptomatic lesions in the mouth. The lesions were stable and had been present
      for 6 years. On physical examination, there were diffuse white, soft, corrugated
      plaques involving the buccal and labial mucosa, oral commissures, and floor of
      the mouth. No other mucosae were affected and there were no skin or nail
      abnormalities. The histologic findings revealed epidermal hyperplasia with
      parakeratosis and intracellular edema in the squamous cell layer. No nuclear
      atypia was observed. A differential diagnosis of three entities is proposed:
      white sponge nevus, leukoedema, and focal epithelial hyperplasia.

PMID- 9263319
TI  - Use of an emollient as a steroid-sparing agent in the treatment of mild to
      moderate atopic dermatitis in children.
AB  - The effectiveness of an emollient as an adjunct to topical corticosteroid therapy
      for the treatment of mild to moderate atopic dermatitis was studied for 3 weeks
      in 25 children 3 to 15 years of age in comparison with corticosteroid therapy
      alone. The adjunctive regimen of a once-daily application each of hydrocortisone
      2.5% cream and of a water-in-oil cream was equivalent in efficacy to the
      comparative regimen of twice-daily applications of hydrocortisone 2.5% cream.
      Both treatment regimens elicited significant improvement in skin condition by day
      7 ( p < 0.005) and further significant improvement by day 14 (p < 0.005). No
      significant differences between the two treatment regimens were observed in the
      rates of improvement (p > 0.545) or in the reductions in mean lesion size (p >
      0.98). No differences were observed in parental evaluations, except for ease of
      application where a slight preference was expressed for the hydrocortisone 2.5%
      cream preparation (p < 0.038). We conclude that emollient adjunctive therapy
      offers a steroid-sparing alternative to topical corticosteroids alone in the
      treatment of mild to moderate atopic dermatitis.

PMID- 9263320
TI  - Q-switched ruby laser treatment of traumatic tattooing induced by pencil point
      puncture in children.
AB  - Traumatic tattoos induced by pencil point puncture in children may result in
      persistent disfigurement if left untreated. The Q-switched ruby laser effectively
      removes darkly colored cutaneous chromophores with minimal disruption of
      unaffected skin. We present a young patient with pencil point induced traumatic
      tattooing of the face, suffered 1 year prior to presentation, who was
      successfully treated with the Q-switched ruby laser with excellent cosmetic
      results.

PMID- 9263322
TI  - What syndrome is this? Aplasia cutis congenita.

PMID- 9263321
TI  - Multiple acquired vascular nodules.

PMID- 9263324
TI  - Accessory nipples and associated conditions.

PMID- 9263323
TI  - Herpes zoster in a 3-month-old infant.

PMID- 9263325
TI  - Survival of Cloudman mouse melanoma cells after irradiation by solar wavelengths
      of light.
AB  - A number of variants of Cloudman S91 mouse melanoma cells that differ with
      respect to the amount of pigment produced are available for study. In this
      report, we compare the photobiological responses of S91/amel, which contains
      about 1 pg of melanin per cell, with S91/I3, which contains about 3 pg/cell.
      Earlier studies had shown that UVC induced more oxidative damage (in the form of
      thymine glycols) in cell line S91/I3 than in S91/amel and that cell line S91/amel
      was more resistant to killing by UVC than S91/I3. The present study finds that
      S91/amel cells are also relatively resistant to killing by near monochromatic UVB
      from a Philips TL01 fluorescent lamp and by near monochromatic UVA from a Philips
      HPW125 lamp. However, when the cells are irradiated with a Westinghouse FS20
      polychromatic lamp, the S91/I3 cells are more resistant than the S91/amel cells.
      These findings cannot be explained on the basis of pigment induction because in
      S91/I3 this is about the same after UVB and FS20, although the maximum is reached
      earlier after UVB. Nor can our findings be explained on the basis of pyrimidine
      dimer formation, which is comparable in the two cell lines regardless of the type
      of irradiation. These results suggest that, with a pigment such as melanin, which
      absorbs light across the visible and ultraviolet ranges of the spectrum, cellular
      responses to monochromatic light do not necessarily predict responses to
      polychromatic mixtures.

PMID- 9263326
TI  - Ganglioside expression in melanomas from Japanese individuals: unusual pattern in
      two patients with metastatic lesions of acral lentiginous melanomas.
AB  - Melanoma among Japanese is rare, and differs in its clinical and histological
      characteristics from that found in Caucasians. In this study, the ganglioside
      expression of melanoma specimens obtained from Japanese was determined and
      compared with previously published data on Caucasians. The ganglioside
      composition of 25 biopsy melanoma specimens, including 13 primary and 12
      metastatic lesions, was studied using thin layer chromatography. Four
      gangliosides (GM3, GD3, GM2, GD2) were most commonly expressed in melanomas in
      Japanese. The expression of gangliosides was quite variable in both primary and
      metastatic melanomas as seen in previous reports. No significant differences were
      observed between gangliosides from primary and metastatic sites. A new type of
      ganglioside expression, in which GM3 was nearly the only ganglioside (> 95%), was
      found in metastatic tumors from two Japanese patients with acral lentiginous
      melanoma (ALM), which is the most common clinical and histopathological type of
      melanoma among Japanese but is very unusual among Caucasians. The patterns of
      expression were similar to those in Caucasians except for the detection of a
      "new" pattern.

PMID- 9263327
TI  - Biological role of tyrosinase related protein and its biosynthesis and transport
      from TGN to stage I melanosome, late endosome, through gene transfection study.
AB  - Tyrosinase-related protein (TRP)-1 is one of the most abundant melanosomal
      glycoproteins involved in melanogenesis. This report summarizes our recent
      research efforts related to the biological role and biosynthesis of TRP-1 and its
      transport from TGN (trans-Golgi network) to the stage I melanosome. Our UV
      irradiation and tyrosinase and TRP-1 cDNA co-transfection studies indicated that
      human TRP-1 is involved in not only melanogenesis but also prevention of
      melanocyte death, which may occur during biosynthesis of melanin pigment in the
      presence of tyrosinase. Furthermore, a coordinated gene interaction was indicated
      between tyrosinase and TRP-1, resulting in upregulation of mRNA and protein
      expression of LAMP (lysosome-associated membrane protein)-1 that would directly
      prevent the tyrosinase-mediated programmed cell death of melanocytes. Similar to
      tyrosinase, however, TRP-1 appears to require a molecular chaperone, calnexin,
      which we have cloned recently. Our cDNA transfection study of tyrosinase with
      calnexin showed clearly the necessity of calnexin in order to have efficient,
      functional activity of melanosomal glycoprotein, especially tyrosinase. Once
      glycosylation is completed, TRP-1 will be transported from TGN to the stage I
      melanosome. At this stage, TRP-1 will have its own target signal, in particular,
      tyrosine-rich leucine residues in cytoplasmic tail. Our TRP-1 cDNA transfection
      and immunoelectron microscopy study shows that TRP-1 will be transported through
      small vesicles, probably non-clathrin-coated type, to large vacuoles, identical
      to the MPR (mannose-6-phosphate receptor)-positive, late endosomes. In this
      transport process a low molecular weight G-protein, rab-7, was isolated from the
      purified melanosomal protein on 2D-PAGE and identified by subsequent sequencing
      and PCR amplification. Confocal microscopy with double immunostaining and
      immunoelectron microscopy confirmed the co-localization of rab-7 and TRP-1 in the
      melanosomes with early stages of maturation (I-HI). Furthermore, this process
      will also be regulated by phosphatidylinositol 3-kinase (PI-3 kinase).

PMID- 9263328
TI  - Electron transfer and photoprotective properties of melanins in solution.
AB  - The polyquinoid nature of eumelanin(s) enables them to couple oxidation of
      electron donors with the reduction of electron acceptors. We have studied the
      ability of synthetic (Sigma) and "biological" (cuttlefish sepia) melanins to
      mediate electron transfer between hydroxybenzene donors (tyrosine, dopa, chemical
      depigmenters) and model acceptors (ferricyanide, tyrosinase). 1) Depending on the
      reductant, melanin either retards or accelerates ferricyanide reduction. Reaction
      kinetics are consistent with a mechanism involving non-interactive binding of
      both hydroxybenzene and ferricyanide to melanin prior to coupled electron
      transfer. 2) Melanins also act as an electron conduit in markedly accelerating
      the tyrosinase-catalyzed oxygenation of p-hydroxyanisole (MMEH). The active
      species appears to be a complex between melanin and MMEH. The magnitude of both
      effects depend on the type of melanin as well as its oxidation state. Sepia
      (eu)melanin appears to protect against UV-induced damage to acid-soluble
      collagen, as judged by irreversible loss of intrinsic collagen fluorescence.
      Photoprotection against this type of damage appears primarily to involve optical
      absorption/scattering by the pigment.

PMID- 9263329
TI  - The role of endothelin-1 in epidermal hyperpigmentation and signaling mechanisms
      of mitogenesis and melanogenesis.
AB  - The paracrine linkage of endothelins (ET) between keratinocytes and melanocytes
      suggested that ETs are intrinsic mediators for human melanocytes in UVB-induced
      pigmentation. In this study, the role of ET-1 in the epidermal hyperpigmentation
      was investigated in vivo and in vitro. The addition of 10 nM ET-1 induced a H-7
      (10 microM) suppressible-increase in tyrosinase activity in cultured human
      melanocytes and was accompanied by elevated levels of tyrosinase and tyrosinase
      related protein-1 mRNA expression as shown by Northern blotting. Analysis of
      signaling mechanisms leading to tyrosinase activation demonstrated the
      involvements of quick translocation of PKC, the H-7 (10 microM) suppressible
      phosphorylation of the threonine residue of several proteins, and highly elevated
      level of cyclic AMP (4-fold over control). Reverse transcription polymerase chain
      reaction (RT-PCR) of RNA isolated from the epidermis of human skin exposed to UVB
      revealed that UVB irradiation with a dose of 2 MED caused a significant increase
      in the expressions of ET-1, IL-1 alpha, and tyrosinase mRNA signals 5 days after
      irradiation. The involvement of ET-1 in UVB-pigmentation was also corroborated by
      the experiments that the extracts of M. Chamomilla, which can act as an
      antagonist for ET-receptor binding-mediated signaling but has no inhibitory
      effect on tyrosinase activity in culture, had a significant inhibitory effect on
      UVB-induced pigmentation in vivo when daily applied immediately after UVB
      exposure to human skin. These findings suggest that ET-1 is an important mediator
      in the epidermis for UVB-induced pigmentation in vivo.

PMID- 9263330
TI  - Comparison of TRPs from murine and human malignant melanocytes.
AB  - Most of our knowledge of the mammalian tyrosinase related protein (TRP)
      activities is derived from studies using murine melanoma models, such as B16 or
      Cloudman S-91 melanocytes. Owing to the high degree of homology between the
      murine and human enzymes, it has been assumed that their kinetic behaviour could
      be similar. However, the protein sequences at the metal binding sites of the
      murine and human enzymes show some differences of possible functional relevance.
      These differences are more significant in the metal-A site than in the metal-B
      site. By using three human melanoma cell lines (HBL, SCL, and BEU), we have
      studied the catalytic abilities of the human melanogenic enzymes in comparison to
      those obtained for the counterpart murine enzymes isolated from B16 melanoma. We
      have found that TRP2 extracted from all cell lines show dopachrome tautomerase
      activity, although the activity levels in human malignant melanocytes are much
      lower than in mouse cells. Reconstitution experiments of the human enzyme
      indicate that TRP2 has Zn at its metal binding-sites. Although mouse tyrosinase
      does not show DHICA oxidase activity, and this step of the melanogenesis pathway
      is specifically catalyzed by mouse TRP1, the human enzyme seems to recognize
      carboxylated indoles. Thus, human tyrosinase could display some residual DHICA
      oxidase activity, and the function of human TRP1 could differ from that of the
      murine protein. Attempts to clarify the nature of the metal cofactor in TRP1 were
      unsuccessful. The enzyme contains mostly Fe and Cu, but the reconstitution of the
      enzymatic activity from the apoprotein with these ions was not possible.

PMID- 9263332
TI  - Endogenous hyperinsulinism: diagnosis, management, and long-term follow-up.
AB  - Persistent hyperinsulinemic hypoglycemia of the neonate (PHHN) usually presents
      in the neonate or infant. Although rare, the possibility of PHHN should be
      considered in all neonates who have unremitting hypoglycemia. Untreated
      hypoglycemia results in severe neurological disability or death. An
      inappropriately elevated serum insulin level and low serum ketone and free-fatty
      acid concentrations in the presence of hypoglycemia confirm the diagnosis. Early
      diagnosis and aggressive medical management have reduced the morbidity associated
      with PHHN. Pancreatic resection is necessary for long-term control of
      hypoglycemia when medical therapy fails. Ninety-five percent pancreatectomy has
      been the procedure of choice at the author's institution and other pancreatic
      centers. However, a review of the authors' experience and of in the English
      language literature has demonstrated a 33% failure rate, requiring further
      surgery or medical management. Furthermore, long-term follow-up showed that
      diabetes develops in most children who undergo 95% pancreatectomy. The high
      failure rate of 95% pancreatectomy and the ultimate development of diabetes in
      virtually all children suggest the alternative approaches should be considered.

PMID- 9263331
TI  - Selective and synergistic activity of L-S,R-buthionine sulfoximine on malignant
      melanoma is accompanied by decreased expression of glutathione-S-transferase.
AB  - L-buthionine-S,R-sulfoximine (BSO) selectivley inhibits glutathione (GSH)
      synthesis. Malignant melanoma may be uniquely dependent on GSH and its linked
      enzymes, glutathione S-transferase (GST) and GSH-peroxidase, for metabolism of
      reactive orthoquinones and peroxides produced during melanin synthesis. We
      compared the in vitro effects of BSO on melanoma cell lines and fresh melanoma
      specimens (n = 118) with breast and ovarian cell lines and solid tumors (n =
      244). IC50 values (microM) for BSO on melanoma, breast and ovarian tumor
      specimens were 1.9, 8.6, and 29, respectively. The IC90 for melanoma was 25.5
      microM, a level 20-fold lower than steady state levels achieved clinically. The
      sensitivity of individual specimens of melanoma correlated with their melanin
      content (r = 0.63). BSO synergistically enhanced BCNU activity against melanoma
      cell lines and human tumors. We followed GSH levels, GST enzyme activity, GST
      isoenzyme profiles and mRNA levels after BSO. BSO (50 microM) treatment for 48 hr
      resulted in a 95% decrease in ZAZ and M14 melanoma cell line GSH levels, and a
      60% decrease in GST enzyme activity. GST-mu protein and mRNA levels were
      significantly reduced in both cell lines. GST-pi expression was unaffected. These
      data suggest that BSO action on melanoma may be related to GSH depletion,
      diminishing the capacity to scavenge toxic metabolites produced during melanin
      synthesis. We report here for the first time that BSO enhancement of alkylator
      action may be related in part to down regulation of GST. BSO may be a clinically
      useful adjunct in the treatment of malignant melanoma.

PMID- 9263333
TI  - Controversies related to the medical and surgical management of hyperthyroidism
      in children.
AB  - The symptoms of Graves disease were first described more that 150 years ago;
      however, therapy remains controversial. Surgery was the only treatment available
      before the development of various drugs and radioiodine. Medication using
      thionamides has become the most commonly used therapy for Graves' disease in
      childhood. Historically, radioiodine has been avoided in children because of the
      presumed risk for carcinogenesis and genetic mutation. More recently, however,
      long-term follow-up studies have shown little support for these concerns and
      radioiodine has become more commonly employed. None of these main forms of
      therapy is without complication, and the decision to use one or the other is in
      part related to the patient, family, or clinician's perceived risk. None of the
      three forms of therapy is directed at the underlying immunologic problem, and
      until such a treatment is found, no consensus regarding the best way to manage
      these children is likely to be achieved. This review examines the benefits,
      complications, and rationale for using the three main forms of therapy for
      childhood hyperthyroidism owing to Graves' disease.

PMID- 9263334
TI  - 131I therapy for pediatric thyroid cancer.
AB  - The treatment of differentiated thyroid cancer occurring in children and young
      adults remains controversial. Because the mortality rate associated with this
      disease is extremely low and recurrence can develop many years after primary
      therapy, it is impossible to perform randomized trials that answer therapeutic
      questions. In previous issues, the topic of thyroid cancer from the surgical
      perspective has been addressed. Herein the authors discuss the techniques and
      applicability of radioactive iodine therapy in the treatment of patients with
      differentiated thyroid cancer. Topics included are indications for treatment as
      well as short- and long-term complications. A discussion of secondary
      malignancies is also provided.

PMID- 9263335
TI  - Medullary carcinoma of the thyroid gland and the MEN 2 syndromes.
AB  - Medullary thyroid carcinoma (MTC) is an uncommon neoplasm in children that
      usually is associated with the multiple endocrine neoplasia (MEN) syndrome types
      2A and 2B and with familial medullary thyroid carcinoma (FMTC). Recently,
      germline mutations in the RET proto-oncogene have been found in patients with
      these syndromes. Thus, with direct DNA testing, kindred members with MEN 2A, MEN
      2B, or FMTC can be identified before clinical of biochemical evidence of MTC
      develops. It has been hypothesized that prophylactic thyroidectomy early in
      childhood, based on a positive genetic test, produces a better clinical outcome
      than thyroidectomy at the time MTC is diagnosed either clinically or
      biochemically. In the present report, the Washington University experience with
      MTC in children with MEN 2A and 2B is reviewed. Sixteen patients with MEN 2A who
      had thyroidectomy based on the biochemical diagnosis of MTC are compared with 14
      children with MEN 2A who underwent prophylactic thyroidectomy based on direct
      genetic testing. In addition, the clinical results of 11 patients with MEN 2B
      treated for MTC are reviewed. After 3 years of follow-up there has been no
      biochemical or clinical evidence of MTC among the 14 children who had
      prophylactic thyroidectomy. Among the 16 children with MEN 2A who had
      thyroidectomy because of elevated basal of stimulated calcitonin levels, four
      (25%) have persistent of recurrent MTC after a mean follow-up period of 7.6
      years. Of the 11 patients with MEN 2B who underwent thyroidectomy during
      childhood, one has died and seven (70%) of the remaining patients have recurrent
      MTC after a mean follow-up period of 11 years. The authors conclude that a
      significant number of children with MEN 2A or MEN 2B, who have clinical of
      biochemical evidence of MTC before thyroidectomy, have persistent or recurrent
      disease after long-term clinical follow-up. The diagnosis by direct DNA testing
      in patients with these syndromes allows prophylactic thyroidectomy before the
      development of extensive local or metastatic MTC.

PMID- 9263336
TI  - Unusual peptide-secreting tumors in adolescents and children.
AB  - Endocrine tumors of the pancreas and intestine are uncommon but challenging
      lesions. Those tumors that arise in the pancreas are typically derived from one
      of the various cell types of the islet of Langerhans and secrete the peptide
      associated with the cell type. In general, the primary tumors are small,
      relatively slow growing, and many are benign. However, certain tumors are
      malignant, more aggressive, and metastasize early, such as gastrinomas,
      glucagonomas, and VIPomas. Many of these tumors can be multicentric, and some may
      arise in the duodenum of small intestines. Tumors that arise more often in the
      intestine are carcinoids and VIPomas. The endocrine effects of many of these
      tumors such as VIPomas or gastrinomas can be life-threatening. A markedly
      elevated level of a specific peptide will generally be sufficient to establish
      the diagnosis. Often, the greatest challenge is localizing the tumor(s). The only
      opportunity for cure is complete surgical excision. Palliation can be accompanied
      through tumor reduction, surgically of with antineoplastic agents (eg,
      doxorubicin and 5-fluorouracil). Palliation from symptoms also can be
      accomplished by blockade of the peptide's secretion of effects. The prognosis is
      variable and depends on cell type, resectability, and presence of metastases.

PMID- 9263337
TI  - Masculinizing and feminizing syndromes caused by functioning tumors.
AB  - Steroidogenic tumors are derived from cells of male and female reproductive
      tracts, adrenal glands, central nervous system, and, to a lesser degree, from the
      liver and pituitary gland. The symptoms caused by these tumors are related to
      their secretory products. Because enzymatic pathways are shared by both adrenal-
      and gonadal-derived tissues, and the conversion of some of these steroids occurs
      in the adipose tissue, positive identification of many lesions cannot be based on
      peripheral blood hormone levels alone, but require complex protocols to improve
      diagnostic accuracy. Furthermore, these tumors often are smaller than the size
      limit of conventional imaging modalities and thus demand more precise imaging
      techniques. Although diagnosis and localization may be challenging, the rewards
      of a positive prognosis, with complete reversal of symptoms, are more likely to
      occur with early detection and treatment. This article is a review of the
      clinical syndromes associated with pediatric steroidogenic tumors; suggested
      strategies to facilitate their diagnosis, localization, and treatment are
      provided.

PMID- 9263338
TI  - Functioning adrenal neoplasms.
AB  - Neoplasms of the adrenal gland may cause increased hormone activity, which has
      profound effects on the growing child. The adrenal gland should be viewed as two
      functionally separate glands: the adrenal medulla and adrenal cortex. Neoplasms
      of the adrenal cortex secrete excess glucocorticoids, mineralocorticoids, or
      androgens. Adrenal medulla neoplasms generally secrete excess catecholamines.
      Understanding the anatomy, embryology, and physiology of the adrenal cortex and
      medulla allows surgeons to diagnose these tumors, prepare the patients for
      surgery, and treat them effectively after resection. Because adjuvant therapy for
      adrenal cortical and medullary tumors is of limited effectiveness, the surgeon's
      role in the treatment of these neoplasms is extremely important.

PMID- 9263339
TI  - Ascending aortic aneurysm with or without features of Marfan syndrome and other
      fibrillinopathies: new insights.
AB  - More than 70 unique fibrillin-1 mutations have been identified in individuals
      with a variety of phenotypic changes. These range from severe neonatal lethal
      forms of Marfan syndrome to adult onset manifestations, mitral valve prolapse
      syndromes to isolated features such as ectopia lentis, Marfanoid body habitus and
      ascending aortic aneurysm and/or dissection. Fibrillin-1 mutations result in
      structurally and functionally defective fibrillin-1 molecules and microfibrils.
      Recent molecular genetic and fibrillin-1 biosynthesis studies suggest that
      individuals with fibrillin-1 abnormalities can be further subdivided into groups
      that are associated with distinct differences in severity and prognosis. In
      recognition of the expanding scope of related connective tissue disorders, we
      propose the terms microfibrillar disorder for disorders affecting fibrillin
      containing microfibrils, and the more narrow concept of fibrillinopathy for
      clinical entities associated with abnormalities of fibrillin-1 or fibrillin-2.
      This latter category includes the previously defined disorders Marfan syndrome,
      congenital contractual arachnodactyly, and forms of ascending aortic aneurysm
      and/or dissection.

PMID- 9263340
TI  - New and future approaches for spinal cord protection.
AB  - The major cause of spinal cord injury, during and after aortic surgery, is based
      on the occurrence of one or more of the three following events: (1) the duration
      and degree of ischemia;(2) failure to re-establish blood flow to the spinal cord
      after the repair; and (3) a biochemically mediated reperfusion injury.
      Clinically, this manifests either as permanent or reversible paraplegia or
      paraparesis, or a neurogenic bladder. For more than 40 years, numerous methods
      have been attempted to prevent paralysis, and some of the newer technical
      innovations include reducing the duration of ischemia, the use of newer
      centrifugal pump distal perfusion techniques, localized hypothermia, intrathecal
      maneuvers, pharmacological agents, angiography, somatosensory-evoked potential
      monitoring, spinal motor-evoked potential monitoring, hydrogen mapping, not
      resecting the posterior aortic wall, the use of stents, and a spectrum of various
      pharmacological agents to prevent reperfusion injury to the spinal cord. Some of
      these techniques and agent seem to be effective at reducing the risk of spinal
      cord injury.

PMID- 9263341
TI  - Retrograde cerebral perfusion (RCP) in aortic arch surgery: efficacy and possible
      mechanisms of brain protection.
AB  - Retrograde cerebral perfusion (RCP) was first introduced to treat air embolism
      during cardiopulmonary bypass (CPB). Its use was reintroduced to extend the
      safety of hypothermic circulatory arrest (HCA) during operations involving an
      open aortic arch. RCP seems to prevent cerebral rewarming during HCA. Both
      clinical and animal data suggest that RCP provides between 10% and 30% of
      baseline cerebral blood flow when administered through the superior vena cava
      (SVC) at jugular pressures of 20 to 25 mm Hg. RCP flows producing jugular venous
      pressures higher than 30 mm Hg may cause cerebral edema. Cerebral blood flow
      generated by RCP is able to sustain some cerebral metabolic activity, yet is not
      able to fully meet cerebral energy demands even at temperatures of 12 degrees to
      18 degrees C. RCP may further prevent embolic events during aortic arch surgery
      when administered at moderate jugular vein pressures (< 40 mm Hg). Clinical
      results suggest that RCP, when applied during aortic arch reconstruction, may
      extend the safe HCA period and improve morbidity and mortality, especially when
      HCA times are more than 60 minutes. RCP applied in patients and severe carotid
      and brachiocephalic occlusive disease may be ineffective, and caution is in order
      when RCP times are greater than 90 minutes.

PMID- 9263342
TI  - Ascending aortic aneurysm and aortic valve disease: what is the most optimal
      surgical technique?
AB  - The merits of separate versus composite valve graft replacement for the treatment
      of patients with ascending aortic aneurysms or dissections associated with aortic
      valve disease remain a controversial issue. Considering all available clinical
      data, the early and late results surprisingly are quite similar between the two
      procedures. However, patient selection criteria and operative technique are
      important. In patients with the Marfan syndrome and in those with significantly
      diseased or destroyed sinuses, composite valve graft replacement is the procedure
      of choice. The "open" (Carrel button) method of coronary reimplantation is
      recommended in almost all cases to minimize the risk of late false aneurysm
      formation. If the aortic leaflets are normal, a valve-sparing aortic root
      remodeling procedure is a reasonable alternative in certain individuals. Separate
      valve graft replacement is still a satisfactory option in other (non-Marfan)
      patients; however, most of the sinuses should be resected, leaving only small
      tongues of aortic wall surrounding the coronary ostia to reduce the risk of late
      aortic root aneurysmal degeneration. In patients with complex prosthetic valve
      endocarditis or multiple paravalvular leaks, homograft aortic root replacement is
      a good option after radical debridement of all infected or devitalized tissue.

PMID- 9263343
TI  - Coagulation disturbance in profound hypothermia: the influence of anti
      fibrinolytic therapy.
AB  - Extensive thoracic aortic resections often require a period of profoundly
      hypothermic circulatory arrest. The extent of surgical dissection, damaging
      effects of cardiopulmonary bypass, and coagulation disturbances of hypothermia
      predispose to bleeding. Although impervious vascular grafts and biological glues
      have made an important contribution to eliminating the vicious cycle of
      transfusion of stored blood and worsening coagulopathy, hemorrhage remains an
      important cause of morbidity in these patients. Thrombin generation by activation
      of the coagulation cascades also leads to excessive fibrinolytic activity with
      the potential to disrupt the hemostatic process. Pharmacological antifibrinolytic
      therapy with aprotinin or other agents has been shown to preserve hemostasis, but
      the efficacy of antifibrinolytic therapy remains unproven in thoracic aortic
      operations with hypothermic circulatory arrest. This report discusses the
      interactions of hypothermia with the coagulation system, together with the
      efficacy of fibrinolytic therapy from existing surgical experience.

PMID- 9263344
TI  - Endovascular stent graft repair of thoracic aortic aneurysms.
AB  - Aneurysmal disease of the thoracic aorta continues to present vexing challenges
      to the aortic surgeon. Not only does the incidence of the disease seem to be
      increasing, but the older population also harbors more comorbidities. In an
      effort to reduce the perioperative mortality and morbidity, surgeons and
      interventional radiologists at Stanford University Medical Center devised a less
      invasive, endovascular stent-graft repair. This report details the results of the
      first 81 patients, and reviews some other pertinent developments. The stent-graft
      is composed of interlocked, self-expanding "Z" stents covered with a woven Dacron
      graft, which can then be introduced through a hollow 27F Teflon sheath under
      fluoroscopic guidance and deployed across the aneurysm. Aneurysms of the
      descending thoracic aorta are most easily treated, but distal arch pathology can
      occasionally be accommodated. A friction seal prevents movement of the stent, and
      complete exclusion of the aneurysm sac from the circulation is usually possible.
      Degenerative aneurysms accounted for the majority of the diseased aortas.
      RESULTS: There were 7 (9% +/- 3%) deaths, 3 directly attributable to the stent
      graft procedure, including two strokes presumably from atheroemboli from the
      aortic arch. Paraplegia occurred in three patients, but in only one with an
      uncomplicated stent-graft placement without protracted hypotension. Two nonfatal
      strokes also occurred. There has been only a single instance of documented late
      graft failure, which resulted in a fatal hemorrhage. Although the long-term
      durability of the stent-grafts in unknown at this early stage, we believe this
      technology to be a significantly less morbid treatment for aneurysmal disease of
      the descending thoracic aorta. Only long-term follow-up will further define its
      utility.

PMID- 9263345
TI  - Pathophysiology of Barrett's esophagus.
AB  - A novel pathophysiology of Barrett's esophagus and a new method of assessing
      biopsy specimens in patients with gastroesophageal reflux disease (GERD) are
      presented. This is based on the observation in autopsy studies of patients
      without GERD that the squamous epithelium of the esophagus transitions directly
      to fundic mucosa in many people and that the cardiac mucosa is of very short
      length in others. Available evidence suggests that what is termed gastric cardiac
      mucosa is in reality an abnormal mucosa resulting from metaplasia of the squamous
      epithelium of the esophagus as a result of GERD. The severity of GERD correlates
      with the length of metaplastic cardiac mucosa and further changes occurring in
      it, permitting development of a system that provides good correlation between
      biopsy histology and severity of GERD. Intestinal metaplasia ("Barrett's
      esophagus") always occurs in this metaplastic cardiac mucosa. The recognition of
      this new pathophysiology of Barrett's esophagus permits identification of the
      entire sequence whereby GERD leads to adenocarcinoma: GERD-->cardiac metaplasia
      of squamous epithelium-->reflux carditis-->intestinal metaplasia-->dysplasia-
      >adenocarcinoma. This article also attempts to develop a terminology that avoids
      use of the confusing term "Barrett's esophagus," which should be discarded.

PMID- 9263346
TI  - Management of Barrett's esophagus free of dysplasia.
AB  - Barrett's esophagus is a condition in which intestinal metaplasia replaces a
      portion of the normal squamous epithelium lining the distal esophagus. It occurs
      as a consequence of chronic gastroesophageal reflux. Patients with Barrett's
      often have both lower esophageal sphincter dysfunction and impaired esophageal
      body motility, and therefore tend to have relatively severe reflux. In addition,
      it is likely that the composition of refluxed material is important in patients
      with Barrett's. There is increasing evidence that Barrett's and complications of
      Barrett's are related to duodenogastric rather than pure gastric reflux. By
      allowing continued duodenogastric reflux, acid suppression therapy may promote
      the development of Barrett's. On the other hand, a functioning fundoplication
      abolishes reflux, ends repetitive injury to the esophageal mucosa, and is
      associated with a decreased incidence of disease progression in patients with
      Barrett's compared with medical therapy. Barrett's is a premalignant condition,
      and all patients should undergo routine endoscopic surveillance. Patients with
      adenocarcinoma detected while on surveillance present at an earlier stage and
      have better survival than patients who present outside a surveillance program. In
      the future, mucosal ablation techniques may allow removal of the metaplastic
      epithelium and eliminate the risk of malignancy.

PMID- 9263347
TI  - Management of Barrett's esophagus with dysplasia.
AB  - Barrett's esophagus is a metaplastic change in the mucosal lining which
      represents a peculiar form of healing in response to the chronic injury due to
      gastroesophageal reflux. It has been recognized that this change is associated
      with an increased risk of developing esophageal adenocarcinoma. Several factors
      have been shown to identify the patients who are at particular risk for
      carcinoma, the most importance of which is the development of dysplasia. As a
      result, management of patients with Barrett's esophagus must include careful
      endoscopic surveillance with histological examination of the biopsies by two
      independent experienced pathologists. Patients with low-grade dysplasia require
      complete control of reflux and careful endoscopic surveillance. Because the
      majority of patients with high-grade dysplasia will have co-existent
      adenocarcinoma, and because of difficulties in differentiating high-grade
      dysplasia from invasive adenocarcinoma, esophagectomy is the treatment of choice
      for these individuals. This approach has been shown to result in a significant
      improvement in survival in patients with esophageal cancer identified under
      surveillance.

PMID- 9263348
TI  - Management of adenocarcinoma arising in Barrett's esophagus.
AB  - Esophageal adenocarcinoma is a highly malignant tumor and, if not diagnosed at an
      early stage, carries a poor prognosis. Controversy exists over how to manage
      carcinoma of the esophagus confined to the mucosa and the extent of resection to
      cure disease that has extended beyond the mucosa. Similarly, there are differing
      opinions regarding the role of adjuvant chemotherapy and the efficacy of surgical
      resection for palliation. These issues are discussed as they pertain to the
      management of adenocarcinoma arising in Barrett's esophagus.

PMID- 9263349
TI  - Erythromelalgia and thrombocythemia: a disease of platelet prostaglandin
      metabolism--thesis, Rotterdam, 1981.

PMID- 9263350
TI  - Proposal for revised diagnostic criteria of essential thrombocythemia and
      polycythemia vera by the Thrombocythemia Vera Study Group.
AB  - The present study revises the criteria of the Polycythemia Vera Group (PVSG) for
      the diagnoses of essential thrombocythemia (ET) and polycythemia vera (PV) in
      view of accumulating data on in vitro cultures of hematopoietic progenitors and
      by adding histopathology from bone marrow biopsies. The majority of ET patients
      show spontaneous megakaryocyte or erythroid growth or both, but in about 35% the
      growth pattern is normal. So far none of the patients with reactive
      thrombocytosis have shown either spontaneous megakaryocyte or erythroid colony
      growth. Virtually all PV patients show spontaneous or endogenous erythroid colony
      (EEC) formation, whereas patients with secondary erythrocytosis and healthy
      controls do not show any erythroid colony growth in the absence of erythropoietin
      (EPO). Some rare patients with a disorder other than a myeloproliferative disease
      (MPD) may show spontaneous growth of erythroid colonies caused by a mutation in
      the EPO receptor. Megakaryocytes in bone marrow smears and biopsy material from
      ET and PV patients are typically increased in number and size. Enlarged
      megakaryocytes with mature cytoplasm and multilobulated nuclei and the tendency
      of these megakaryocytes to cluster in a normal or slightly increased cellular
      bone marrow represent the diagnostic hallmark of ET. Increase and clustering of
      enlarged, mature, and pleiomorphic megakaryocytes in a moderate to marked
      hypercellular bone marrow with hyperplasia of dilated sinuses is the diagnostic
      feature of untreated PV. In reactive thrombocytosis and secondary erythrocytosis
      the size and morphology of megakaryocytes remain normal and there is no tendency
      of the megakaryocytes to cluster. Both spontaneous EEC and histopathology of bone
      marrow biopsies appear to offer specific clues to the diagnosis of overt and
      latent ET or PV and have the potential to differentiate ET from reactive
      thrombocytosis and PV from secondary erythrocytosis. Moreover, bone marrow
      histopathology has the diagnostic power to distinguish and to stage the various
      MPDs without regard to clinical and laboratory data.

PMID- 9263351
TI  - Aspirin and platelets: the antiplatelet action of aspirin and its role in
      thrombosis treatment and prophylaxis.
AB  - The antithrombotic action of aspirin (acetylsalicylic acid) is due to inhibition
      of platelet function by acetylation of the platelet cyclooxygenase (COX) at the
      functionally important amino acid serine529. This prevents the access of the
      substrate (arachidonic aid) to the catalytic site of the enzyme at tyrosine385
      and results in an irreversible inhibition of platelet-dependent thromboxane
      formation. Aspirin is an approximately 150- to 200-fold more potent inhibitor of
      the (constitutive) isoform of the platelet enzyme (COX-1) than the (inducible)
      isoform (COX-2) which is expressed by cytokines, inflammatory stimuli, and some
      growth factors. This explains the different dosage requirements of aspirin as an
      antithrombotic (COX-1) and an anti-inflammatory drug (COX-2), respectively.
      Aspirin is the "gold standard" antiplatelet agent for prevention of arterial
      thromboses. The optimum dose of aspirin as an antithrombotic drug can differ in
      different organ circulations. While 100 mg/day is sufficient for prevention of
      thrombus formation in the coronary circulation, higher doses may be required for
      the prevention of vascular events in the cerebral and peripheral circulation.
      However, any effective antiplatelet dose of aspirin is associated with an
      increased risk of bleeding. Therefore, the individual benefit/risk ratio
      determines the administration of the compound. There are no known prostaglandin
      independent mechanisms for the antithrombotic action of aspirin in clinical use.
      Thus, platelet activation caused by other factors remains unchanged and might
      result in a resistance against inhibition of platelet function by aspirin. This
      involves platelet activation by shear stress and ADP. Additionally, there is no
      "sparing" of endothelial prostacyclin synthesis in clinical conditions of
      atherosclerotic endothelial injury. In this case, inhibition of COX-1 by aspirin
      will also reduce the amount of precursors for vascular prostacyclin synthesis,
      provided, for example, from adhering platelets.

PMID- 9263352
TI  - Erythromelalgia: a pathognomonic microvascular thrombotic complication in
      essential thrombocythemia and polycythemia vera.
AB  - Erythromelalgia is a characteristic thrombotic complication in patients with the
      myeloproliferative disorders, essential thrombocythemia and polycythemia vera. In
      this minireview, which is based on more than 20 years of clinical observations
      and intervention studies, the clinical manifestations, treatment, and
      pathogenesis of erythromelalgia are discussed.

PMID- 9263353
TI  - Neurologic and visual symptoms in essential thrombocythemia: efficacy of low-dose
      aspirin.
AB  - Neurologic and visual symptoms frequently occurred in 56 reported patients with
      essential thrombocythemia (ET). They may either precede or follow the well-known
      microcirculatory complications of ET of acroparesthesias, erythromelalgia, and
      acrocyanosis or ischemia of one or more toes. In comparison with transient
      ischemic attacks in patients with vascular risk factors, the usual neurologic
      presentation of ET consists of brief attacks of sudden cerebral or visual
      dysfunction, which can be either well localized or diffuse and entirely
      nonspecific. A dull and throbby headache usually lasting for several hours
      frequently accompanies the neurologic symptoms. Visual symptoms are less frequent
      and include transient monocular blindness and global symptoms such as
      scintillating scotomas and attacks of blurred vision. Neurologic and visual
      symptoms may leave minor sequelae but are generally nondisabling. The striking
      similarity to migraine, together with the absence of vascular risk factors and
      the striking efficacy of aspirin treatment supports the hypothesis that the
      ischemic neurologic and visual symptoms in ET are caused by shear rate-induced
      intravascular activation and aggregation of platelets with subsequent transient
      sludging or occlusion of the cerebral arterial microvasculature. Available data
      show that both the erythromelalgic distress and the ischemic neurologic attacks
      in ET are completely abolished by control of platelet function with low dose
      aspirin alone or reduction of platelet counts to normal as well as by the
      combination of platelet reducing therapy and low-dose aspirin. Early recognition
      and appropriate treatment of neurologic symptoms in patients with ET is therefore
      of great clinical relevance.

PMID- 9263354
TI  - Aspirin in essential thrombocythemia: status quo and quo vadis.
AB  - Aspirin has a well established role in the prevention of arterial thrombosis.
      Discussion on the efficacy and safety of aspirin in the treatment and prophylaxis
      of thrombosis in essential thrombocythemia (ET) has become an important issue.
      The rationale for its use in ET comes from the observation that arterial
      thrombosis and platelet-mediated microcirculatory disturbances are the major
      causes of morbidity and mortality in ET. Experimental data have shown
      persistently elevated levels of thromboxane A2 (TXA2) in ET patients probably
      reflecting an enhanced in vivo platelet activation. Increased TXA2 biosynthesis
      and platelet activation in vivo in ET are selectively suppressed by repeated low
      doses of aspirin. ET-related symptoms such as erythromelalgia, transient
      neurologic and ocular disturbances are sensitive to aspirin. However, the benefit
      of low-dose aspirin is still uncertain in the primary prevention of thrombosis in
      ET. Furthermore, aspirin may unmask a latent bleeding diathesis frequently
      present in ET which may result in severe hemorrhagic complications. Thus, aspirin
      is contraindicated in ET patients with a bleeding history or a very high platelet
      count (> 1500 x 10(9)/L) leading to the acquisition of von Willebrand factor
      deficiency. If indicated, aspirin is presently used in the widely accepted low
      dose regimen of 100 mg daily. However, an optimal effective dose has not yet been
      established. To further evaluate the efficacy and safety of aspirin in ET,
      prospective clinical trials are needed.

PMID- 9263355
TI  - Anagrelide as a new platelet-lowering agent in essential thrombocythemia:
      mechanism of actin, efficacy, toxicity, current indications.
AB  - Anagrelide is an oral imidazoquinazoline agent with an anti-cyclic AMP
      phosphodiesterase activity and inhibits platelet aggregation in both humans and
      animals. In addition, it has in humans a species-specific platelet-lowering
      activity observed at dose levels lower than those required to inhibit platelet
      aggregation. Because of this, the drug has been tested in patients with clonal
      thrombocytosis and has been shown to have potent platelet-reducing activity in
      essential thrombocythemia (ET) and related disorders. The mechanism of action may
      involve the drug's interference with megakaryocyte maturation. More than 90% of
      patients with ET respond to anagrelide regardless of the presence or absence of
      previous therapy. The responses are durable with a median maintenance dose of
      approximately 2 to 2.5 mg/day. Side effects are related mostly to the drug's
      direct vasodilating and positive inotropic effects and include headache, fluid
      retention, tachycardia, and arryhthmias. The place of anagrelide therapy in the
      current management of patients with ET is discussed.

PMID- 9263356
TI  - The paradox of bleeding and thrombosis in thrombocythemia: is von Willebrand
      factor the link?
AB  - Thrombosis and bleeding, reflecting the extreme ends of hemostasis, are common
      complications in patients with thrombocythemia in its primary form or in
      association with polycythemia vera. The pathogenesis of these thrombohemorrhagic
      predispositions is not clearly understood. In the present study we describe the
      paradoxical and sequential occurrence of thrombotic and bleeding complications in
      six patients with thrombocythemia. Strikingly, in all patients some abnormality
      of plasma von Willebrand factor was detected. The potential role of von
      Willebrand factor in the pathogenesis of these hemostatic complications is
      discussed.

PMID- 9263357
TI  - Relation of platelet abnormalities to thrombosis and hemorrhage in chronic
      myeloproliferative disorders.
AB  - The chronic myeloproliferative disorders (MPD), predominantly polycythemia vera
      and essential thrombocythemia, are characterized by a high incidence of
      thromboembolic and, to a lesser degree, hemorrhagic complications. The disease
      process in chronic MPD affects a pluripotent progenitor cell and results in
      trilineage hematopoietic proliferation. Clonal involvement of
      megakaryocytopoiesis is regarded as the main origin of thromboembolism in MPD and
      results in abnormal platelet production. These platelets show increased size
      heterogeneity and ultrastructural abnormalities, and their function in vitro is
      in many ways impaired with a high degree of individual variability. Elevated
      levels of platelet-specific proteins, increased thromboxane generation, and
      expression of activation-dependent epitopes on the platelet surface are common on
      chronic MPD, and may reflect an inappropriate state of platelet activation.
      Although a variety of platelet receptor deficiencies and some defects of
      intracellular signaling pathways have been identified, the different platelet
      defects in MPD could not be traced back to an underlying general pathogenetic
      mechanism. On progression of chronic MPD to more advanced stages of the disease,
      the number of platelet abnormalities tend to increase. Cytoreductive drugs may
      partly improve platelet dysfunction, and platelet inhibitory agents reduce
      symptoms of platelet activation. However, neither of these therapeutic principles
      is able to normalize platelet function in MPD. As an alternative to conventional
      treatment, specific suppression of clonal megakaryocyte growth and recovery of
      polyclonal hematopoiesis may be achieved by biologic agents such as interferon
      alpha. Such treatment strategies may prevent thromboembolic complications
      together with hematologic symptoms and progression of the disease and should be
      further evaluated in prospective studies.

PMID- 9263358
TI  - Risk factors for genital ulcerations in Kenyan sex workers. The role of human
      immunodeficiency virus type 1 infection.
AB  - BACKGROUND AND OBJECTIVES: Genital ulcer disease (GUD) is a major risk factor for
      human immunodeficiency virus (HIV) transmission. Cross-sectional studies have
      suggested that HIV infection may itself predispose to genital ulceration (GU).
      GOAL: To prospectively study the effects of HIV type 1 (HIV-1) infection and
      behavioral variables on GU incidence. METHODS: A cohort of 302 Kenyan female sex
      workers was established in April 1991. Women were scheduled for assessment every
      2 weeks, and bloods were collected every 6 months for HIV serology, rapid plasma
      reagin (RPR) and CD4 counts. Logistic regression was used to study risk factors
      for incident genital ulcers. RESULTS: 189 women (62.5%) had at least one incident
      ulcer over 24.3 +/- 15.3 months. GU incidence was higher in seropositive than
      initially seronegative women (82% vs. 48%; odds ratio [OR]) = 4.33; P < 0.01).
      Only HIV-1 seropositivity (OR = 3.42), a CD4 count < 200/ml (OR = 1.94), and oral
      contraceptive use (OR = 1.35) were associated (P < 0.05) with GU incidence in
      regression analysis. For those ulcers where an etiology was actively sought,
      Hemophilus ducreyi was confirmed in 54 (19%) of cases, and syphilis in 30 (29%).
      CONCLUSION: GU incidence in Kenyan sex workers is independently affected by HIV-1
      serostatus, degree of immunosuppression, and oral contraceptive use.

PMID- 9263359
TI  - Factors associated with appropriate physician management of sexually transmitted
      diseases in an urban Canadian center.
AB  - BACKGROUND AND OBJECTIVES: To explore physicians' management of selected sexually
      transmitted diseases (STDs), because previous studies suggest that physicians'
      management practices could be improved. GOALS: To determine the estimated annual
      incidence of STD seen by family/general practitioners (FPs), gynecologists (GYNs)
      and urologists (UROLs), adequacy of STD management practices, and any
      associations with demographic and other characteristics. STUDY DESIGN: A self
      administered questionnaire was mailed to GYNs, UROLs, and a random sample of FPs
      in Hamilton, Ontario. RESULTS: Eighty-one of 102 (79.4%) FPs, 27 of 32 (84.4%)
      GYNs, and 7 of 8 (87.5%) UROLs responded. Vaginitis, male urethritis, and genital
      warts in women were the most frequently observed STDs. The treatment of bacterial
      vaginosis and pelvic inflammatory disease were most frequently at variance with
      published guidelines. CONCLUSIONS: Deficiencies exist in physicians' management
      of both common and potentially serious STD problems.

PMID- 9263360
TI  - Neurocognitive impairment in human immunodeficiency virus infection is correlated
      with sexually transmitted disease history.
AB  - BACKGROUND AND OBJECTIVES: Neurocognitive impairment is common in human
      immunodeficiency virus (HIV)-infected subjects. The relationship of sexually
      transmitted diseases to neurocognitive changes is unknown. GOAL: To establish
      whether HIV-infected patients with a history of syphilis or gonorrhea have a
      higher rate of neurocognitive dysfunction. STUDY DESIGN: Neurocognitive function
      was measured by a battery of quantitative tests in a 453-person HIV-infected
      cohort and a 219-person HIV-seronegative control group. Neurocognitive function
      was then correlated with histories of either syphilis or gonorrhea to assess for
      possible relationships between these sexually transmitted diseases and neurologic
      impairment. RESULTS: Human immunodeficiency virus-infected subjects with a
      history of either syphilis or gonorrhea tended to perform worse on neurocognitive
      testing than their counterparts. This difference could not be explained by
      educational attainment, age, race or CD4 cell count, and was not noted in the HIV
      uninfected control subjects. CONCLUSIONS: Sexually transmitted diseases in HIV
      infected subjects are correlated with neurocognitive impairment through an
      unidentified mechanism.

PMID- 9263361
TI  - Reasons for not using condoms of clients at urban sexually transmitted diseases
      clinics.
AB  - BACKGROUND AND GOAL: Greater understanding of the factors related to inconsistent
      condom use is essential in the development of strategies to promote condom use
      among clients who access public, inner-city sexually transmitted diseases (STD)
      clinics. Therefore, this study aimed to explore reasons for not using condoms
      among 260 predominantly African American heterosexual male and female clients
      presenting for care at two inner-city STD clinics. STUDY DESIGN: Clients selected
      for this descriptive analysis reported having had at least one unprotected
      episode of sexual intercourse in the last 10 episodes. In face-to-face
      interviews, clients provided information about sexual activity, sexual partners,
      and condom use in the previous 30 days. In addition, they were asked to indicate
      the main reason for not using condoms when having unprotected sex. RESULTS:
      Content analysis showed six major categories of reasons for not using condoms:
      reasons related to partner relationships, reasons related to sexual sensation,
      reasons related to situational constraint, reasons related to condoms themselves,
      reasons related to pregnancy, and reasons related to types of sexual activity.
      Most frequent explanations given for not using condoms included partner trust
      (19.6%), the feel of condoms (11.9%), and lack of condom availability (11.5%).
      Clients also reported barriers to condom use that included beliefs about condom
      sensation and partner relationships. CONCLUSIONS: These results show the
      continued barriers that exist with respect to condom use in at-risk populations
      and emphasize the need to tailor meaningful interventions in order to promote
      condom use among persons who, for differing reasons, choose not to use them.

PMID- 9263362
TI  - Molecular epidemiology of infections with Neisseria gonorrhoeae among visitors to
      a sexually transmitted diseases clinic.
AB  - OBJECTIVES: To identify determinants for plasmid-mediated resistance to
      penicillin (penicillinase-producing Neisseria gonorrhoeae [PPNG]) and
      tetracycline (tetracycline-resistant N. gonorrhoeae [TRNG]) among gonococci, to
      determine the distribution of bacterial characteristics, and to correlate these
      with antibiograms and patient characteristics. STUDY DESIGN: Gonococcal isolates
      from 131 patients attending a sexually transmitted diseases clinic in The
      Netherlands in 1994 were auxotyped and serotyped and antimicrobial susceptibility
      was tested. Information on patient characteristics was collected at the initial
      visit. RESULTS: The most prevalent serotype, IB-1 (26%), proved to be related to
      sexual contact with casual partners, especially commercial sex partners. In
      addition, IB-1 strains were associated with PPNG and displayed higher minimum
      inhibitory concentrations (MICs) for ceftriaxone, cefuroxime, and ciprofloxacin.
      Homosexual men were more often infected with nonrequiring, IB-2, and IB-6 strains
      than heterosexuals. These strains were very sensitive to ceftriaxone and
      ciprofloxacin. Overall, one strain showed decreased susceptibility to
      ciprofloxacin (MIC 0.5 microgram/ml), but no resistance to ceftriaxone,
      ciprofloxacin, or cefuroxime was observed. However, 31% of the isolates were
      TRNG, PPNG, or both. Determinants for these resistant strains among men were the
      use of antibiotics (odds ratio [OR] = 4.8, 90% confidence interval [CI] 1.3
      19.1), Surinam or Morrocan origin (OR = 3.3, 90% CI 1.3-8.4), and homosexual
      contacts (OR = 0.1, 90% CI 0.03-0.4). CONCLUSIONS: Different types, with variable
      susceptibility, were associated with homosexual and commercial sexual behavior.
      PPNG and TRNG were more commonly isolated from antibiotic users, heterosexual
      individuals, and ethnic minorities. Continuous surveillance of susceptibility is
      needed to follow the spread of PPNG and TRNG and to detect resistance to the
      currently recommended agents in a timely fashion.

PMID- 9263363
TI  - Risky behavior in women with history of casual travel sex.
AB  - OBJECTIVES: To define epidemiologic and psychosocial characteristics in women
      with a history of casual travel sex abroad. STUDY DESIGN: The participants
      consisted of 996 women attending for contraceptive advice, of whom 276 admitted
      that they had experience of casual travel sex. The remaining women served as a
      comparison group. In structured interviews, questions were asked about
      educational level, partnerships, reproductive history, contraceptive and drug
      use, smoking, and psychosocial factors such as wariness, success, and
      attractiveness. RESULTS: The women with experience of casual travel sex were more
      often single, had more often experienced broken relationships, were more often
      smokers, and used alcohol or cannabis at a higher-frequency. Their educational
      level was higher and a history of induced abortions was more common. CONCLUSIONS:
      The results of this study indicate that women with experience of casual travel
      sex not only take sexual risks, but take other risks that might impose danger to
      their health.

PMID- 9263364
TI  - Comparisons of cost and accuracy of DNA probe test and culture for the detection
      of Neisseria gonorrhoeae in patients attending public sexually transmitted
      disease clinics in Los Angeles County.
AB  - BACKGROUND: Strict handling and transport requirements for the successful use of
      culture in the detection of Neisseria gonorrhoeae warrant investigation of
      accurate and cost-effective test alternatives such as the Gen-Probe PACE 2 DNA
      probe assay (Gen-Probe, Inc., San Diego, CA). STUDY DESIGN: The Gen-Probe PACE 2
      DNA probe assay for N. gonorrhoeae was compared with conventional culture methods
      in the principal Los Angeles County (LAC) Department of Health Services (DHS)
      Public Health Laboratory and three of its branch laboratories. Urethral and
      endocervical samples were collected from 1,566 patients (921 males; 645 females)
      attending six LAC DHS sexually transmitted disease clinics. Cost analysis was
      performed comparing material and labor costs of the two test methods. RESULTS:
      The overall prevalence based on culture was 11.8% (15.7% for males; 6.4% for
      females). Nine samples were culture positive, Gen-Probe negative and four samples
      were culture negative, Gen-Probe positive and remained discordant after
      discrepant analysis. The sensitivity and specificity were 94.6% and 99.7%,
      respectively, for the PACE 2 assay compared with culture. The positive and
      negative predictive values were 97.8% and 99.3%, respectively. No statistically
      significant difference was found between the two tests. A cost analysis found an
      average cost of $3.11/test for culture and $3.85/test for PACE 2, given the
      approximate 12% disease prevalence in this population. CONCLUSIONS: Gen-Probe's
      PACE 2 assay may provide an acceptable, cost-effective alternative to culture,
      especially among high-risk males.

PMID- 9263365
TI  - Feasibility and yield of screening urine for Chlamydia trachomatis by polymerase
      chain reaction among high-risk male youth in field-based and other nonclinic
      settings. A new strategy for sexually transmitted disease control.
AB  - BACKGROUND: Inner-city youth are at disproportionate risk for Chlamydia
      trachomatis infection. Identification of infected individuals is hampered by the
      often asymptomatic nature of infection and access and utilization barriers to
      clinic-based screening services. The feasibility and yield of screening urine for
      C. trachomatis by polymerase chain reaction was studied among high-risk male
      youth outside traditional clinic settings. METHODS: As part of a community-level
      sexually transmitted disease (STD) prevention program among high-risk youth in
      Denver, outreach workers enrolled subjects, administered questionnaires, and
      collected first-catch urine samples in nonclinical facility-based and field-based
      settings. Facility settings consisted of community/recreation centers, high
      schools, and an STD/human immunodeficiency virus prevention storefront. Field
      settings included alleys, parking lots, parks, and residences. Individuals who
      tested C. trachomatis positive were contacted by program outreach workers and
      provided with standard treatment and partner notification services. RESULTS: Over
      a 20-month period, 486 urine specimens were collected, 32 (6.6%) of which were C.
      trachomatis positive. Rates were higher for subjects screened in the field than
      in facility settings (11.9% vs. 4.4%, P < 0.05). Subjects with chlamydial
      infection were more likely to have had vaginal intercourse in the previous 30
      days (adjusted odds ratio: 2.9) and to have been recruited in field settings
      (adjusted odds ratio: 2.5). Of subjects with chlamydial infection, 31/32 (97%)
      were treated within a median of 8 days after urine collection. CONCLUSIONS: Urine
      chlamydial screening by polymerase chain reaction of sexually active male youth
      in nontraditional settings appears to be feasible and to provide yields similar
      to those reported in standard clinic settings. Evaluation of samples easily
      collected in nonclinic locations holds great promise as an additional strategy
      for the control of chlamydial infection and other STD among difficult-to-reach
      populations.

PMID- 9263366
TI  - Definitions of genital ulcer disease and variation in risk for prevalent human
      immunodeficiency virus infection.
AB  - OBJECTIVES: Although genital ulcer disease (GUD) has been associated with human
      immunodeficiency virus (HIV) infection in a number of studies, definitions of
      genital ulceration have varied. The authors hypothesized that the association of
      GUD with prevalent HIV infection may vary according to the definition of GUD that
      is used. METHODS: As part of a prospective cohort study, 863 patients were
      interviewed and examined who presented to a sexually transmitted disease (STD)
      clinic for new symptom evaluation and who agreed to HIV testing to determine
      demographic and behavioral risk associated with prevalent HIV infection. To
      determine the association between GUD and prevalent HIV, the following
      definitions of GUD were used: observed ulcers, history of syphilis, serologic
      evidence of syphilis, observed culture-proven genital herpes, and serologic
      evidence of herpes simplex virus type II (HSV-2) infection. RESULTS: Of 481 men
      and 382 women enrolled, prevalent HIV infection was detected in 12.5% and 5.2%,
      respectively. In multivariate analyses controlling for known HIV risk behaviors,
      prevalent HIV infection was associated with observed GUD (odds ratio [OR] = 2.0,
      95% confidence intervals (CI) = 1.0-3.9), a history of syphilis (OR = 6.0, CI =
      2.8-12.7), and serologic evidence of syphilis (OR = 3.7, CI = 1.9-7.0), but not
      with serologic evidence of HSV-2 (OR = 1.2, CI = 0.7-2.1), nor with observed HSV
      2 culture-positive genital ulcerations (OR = 1.0, CI = 0.4-4.2). Factors
      contributing to different strengths of association between HIV infection and a
      history of syphilis or serologic evidence of syphilis included the presence of
      underdiagnosed syphilis infection in people with reactive serologic tests and the
      absence of serologic reactivity in people with a positive history. CONCLUSIONS:
      Although GUD is strongly associated with prevalent HIV, the strength of the
      association depends on the definition of GUD used. For accurate evaluation of
      people at risk for HIV, clinicians and researchers should use multiple
      definitions of GUD.

PMID- 9263367
TI  - A model of human aiming movements applied to Parkinson's disease.
AB  - Healthy control subjects and Parkinsonian patients with and without l-DOPA
      medication were tested in a motor paradigm. The subjects were instructed to aim
      with the forearm as fast and as accurately as possible to the illuminated target.
      A quantitative dynamic model for planning and execution of voluntary aiming
      movements is developed. The proposed 'motor model' reproduces Parkinsonian
      symptoms and the therapeutic effects of the drug. The proposed model implies that
      the basal ganglia store movement and limb specific parameters which are necessary
      for the control of voluntary aiming movements. The model is contrasted against
      analytic concepts of motor control. Analytic concepts assume that movements are
      planned in space coordinates and then transformed to neural activities
      corresponding to the muscle force. In contrast, the neuronal activities simulated
      in the proposed 'motor model' can not be described by the terms 'planned
      trajectory', 'muscle force' or similar terms but suggest a more abstract dynamic
      concept.

PMID- 9263368
TI  - Implant dentistry--development and current focus.
AB  - Today, implant dentistry plays an important role in the maintenance of chewing
      function and oral health. For thirty years now oral implants and methods for
      implantation have been developed further to assure a lifetime stability of these
      devices and to optimize function and esthetics. Starting with the treatment of
      fully edentulous patients, oral implants are now used for the reconstruction of
      partially edentulous patients as well. Thereby, implants not only replace missing
      teeth but also help to preserve intact remaining teeth. They are usually
      incorporated to improve the patient's subjective chewing comfort. The present
      paper gives an overview of the development and the current state of the art of
      oral implants, as well as their clinical indications.

PMID- 9263369
TI  - Analysis of ultrasonic Doppler velocity data obtained in models of stenosed
      carotid bifurcations with irregular lesion surface.
AB  - In this study properties are concerned of ultrasonic Doppler spectra recorded
      distal to an irregularity localised in the internal carotid artery of a true-to
      scale elastic model of a severely stenosed carotid bifurcation. Four models
      differing in irregularity were obtained by melting graded holes in the original
      wax cast, about 5-7 mm distal to the bifurcation. Velocity data were collected
      using an HP Sonos 2500 ultrasonograph working in pulsed Doppler mode. The
      observed effect of the irregularity with respect to the smooth wall model
      consisted in: (1) presence of a reduced flow zone 15 mm distal to the severe
      irregularity situated at the outer wall of the model in the ICA branch; (2)
      presence of a recirculation zone 15 mm distal to the severe irregularity situated
      at the inner wall of this model; (3) negative values of the measure of symmetry
      of the Doppler spectrum and (4) decreased values of relative width of Doppler
      spectra obtained 25 mm distal to the bifurcation in models with severe
      irregularity. The alterations of flow distribution and Doppler spectra depend on
      the geometry of the model under investigation and this study provides an
      indication as to what phenomena can happen in a model of stenosed carotid
      bifurcation with irregular lesion surface and how these phenomena may affect the
      ultrasonic Doppler spectra. Such information could be used in the evaluation of
      the risk of cerebral embolism.

PMID- 9263371
TI  - Approach to computer-based medication planning and coordination support in
      intensive care units.
AB  - Due to more and more complex diagnosis and therapy measures, the critical care of
      patients requires an extensive work organisation which comprises patient,
      doctors, nurses and external services (e.g., central laboratory). In this
      organisation, the documentation plays a major role for the planning and
      coordination of work procedures and information flow within the medical staff.
      Various studies in intensive care units (ICU) reveal that the complex work
      organisation and the related information flow are faulty. Breakdowns are often
      caused by a lack of coordination between doctors and nurses and by poor
      transparency of work procedures. A typical example is the incorrect application
      of a doctor's medication orders by a nurse because she might have overseen a plan
      modification. This intransparency increases the strain on the medical staff and
      might result in critical effects on the patient. One approach to design a
      computer support for medication planning as well as the coordination when
      executing medication plans is given by work flow models. This paper shows that
      work flow models could be used to improve deficiencies in medication planning and
      coordination. Furthermore, it is demonstrated how such a support can be mediated
      to the user through an appropriately designed user interface.

PMID- 9263370
TI  - Imaging of the orifice of the left ventricular outflow tract: technique and
      initial results.
AB  - The mechanism of left ventricular outflow tract (LVOT) obstruction in the patient
      after mitral valve replacement or repair was examined with the aid of 2D
      echocardiography. For the interpretation of the spatial relationship between the
      aortic root and mitral annulus, however, the 2D display is sometimes inadequate
      since it may not simultaneously capture these structures in each center. We
      developed a method to clarify this relationship in 3D based on magnetic resonance
      images. We defined the office of the left ventricular outflow tract (LVOT
      orifice), consisting of, in turn, a muscular region, i.e., edge of the
      interventricular septum, and an annular region, i.e., the annulus of the anterior
      mitral leaflet. In this paper we present image data obtained from one of eight
      normal subjects examined and compare this with data of one of two patients who
      preoperatively suffered degenerative mitral regurgitation and subsequently
      underwent chordal-preserving mitral valve replacement, in which anterior chordae
      were reattached to the anterior annulus. In the normal subject, the mitral
      annulus exhibited a flexible change in shape during the systole, maintaining
      sufficient LVOT orifice size. In the patient, the prosthetic valve exhibited
      translational motion during systole, resulting in dynamic LVOT obstruction. This
      phenomenon was also observed in one other case. Furthermore, the lateral view of
      the LVOT orifice revealed a projection of the prosthetic valve into the LVOT,
      causing mechanical LVOT obstruction. The finding that translational motion of the
      prosthetic valve with an inflexible mitral annulus results in dynamic LVOT
      obstruction may support the hypothesis that annular rigidity causes dynamic LVOT
      obstruction after mitral valve repair with a rigid prosthetic ring.

PMID- 9263372
TI  - Maximising the cost effectiveness of BMD referral for DXA using ultrasound as a
      selective population pre-screen.
AB  - Bone mineral density (BMD) referral for dual energy X-ray absorptiometry (DXA) is
      generally based upon agreed clinical referral criteria (CRC). The aim of this
      study was to determine whether ultrasound measurements of Broadband UI-trasound
      Attenuation (BUA) and velocity (VOS) provide a superior selective pre-screen
      referral method for BMD assessment by DXA. 107 women aged 60-69 years (64.2 +/-
      2.8) had BMD measurements at lumbar spine and right femoral neck along with
      ultrasound BUA and VOS measurements of the left calcaneus. Each subject completed
      an extensive clinical and social questionnaire to ascertain those who would have
      met one or more of the five general clinical referral criteria adopted by our
      Centre. Each subject was classified by DXA using the WHO criteria as normal,
      osteopenic or osteoporotic at lumbar spine or femoral neck. The cost per
      osteoporotic subject correctly identified was calculated. As a reference, based
      upon DXA measurements alone on all 107 subjects, the cost per osteoporotic
      subject identified would be Ponds 185. If subjects had been referred using the
      clinical referral criteria the cost is Ponds 171. For assessment of referral by
      BUA or VOS, an additional charge for ultrasound measurement of all subjects was
      incorporated. At a BUA of 60 dB MHz-1 the cost per osteoporotic subject is Ponds
      107. Ultrasound velocity or a combination of BUA or VOS with clinical referral
      criteria did not provide a significantly reduced cost than the current clinical
      referral criteria alone. This study has demonstrated that BUA provides an
      improved referral procedure to that currently achieved with clinical referral
      criteria and supports the concept of BUA being used as a selective pre-screen for
      DXA in 7th decade subjects.

PMID- 9263373
TI  - Neural network method to determine the vigilance levels of the central nervous
      system, related to occupational chronic chemical stress.
AB  - The effects of chronic toxic occupational factors and functional disorders of the
      central nervous system (CNS) in chemical industry were studied. These factors
      cause various stages of chronic chemical stress on the human CNS together with
      changes of the vigilance levels. On the basis of QEEG data analysis and
      psychometric tests we identified three stages of occupational chemical stress
      syndromes according to the CNS vigilance level (ordered from light to severe):
      hypersthenic syndrome, hyposthenic syndrome, and organic psychosyndrome. Each
      syndrome is characterized by specific changes in the QEEG data. A perceptron
      based neural network was developed for the classification of the QEEG data to one
      of the above-mentioned syndrome classes. The data of 77 patients and 10 healthy
      subjects were selected to test the algorithm. Different combinations of the QEEG
      data as input features to the classifier were chosen. The most reliable
      classification was obtained when QEEG data measured during the visual stimulation
      of the CNS were used. However, sometimes the algorithm was unable to solve the
      classification problem, or it took a very long time to train the perceptron. In
      part, difficulties arose from using a perceptron-based algorithm, which can
      classify only linearly separable data.

PMID- 9263374
TI  - Single-dose pharmacokinetics and pharmacodynamics of oral triazolam in relation
      to cytochrome P4502C19 (CYP2C19) activity.
AB  - Previous studies have suggested that triazolam is at least partly metabolized by
      cytochrome P4503A4 (CYP3A4). However, no study has examined the relationship
      between the metabolism of triazolam and CYP2C19, which is involved in the
      metabolism of diazepam. Therefore, the single-dose pharmacokinetics and
      pharmacodynamics of oral triazolam were studied in relation to the CYP2C19 status
      assessed by the S-mephenytoin 4-hydroxylation capacity in 12 healthy male
      volunteers, consisting of seven extensive metabolizers (EMs) and five poor
      metabolizers (PMs) of S-mephenytoin 4-hydroxylation. Each subject was
      administered a single oral dose of 0.5 mg of triazolam, and blood was sampled up
      to 12 hours after the dosing. Psychomotor function was assessed by the Digit
      Symbol Substitution test, Visual Analogue Scale, and Udvalg for Kliniske
      Undersogelser (UKU) scale. Plasma triazolam concentrations were measured by high
      performance liquid chromatography. There were no significant differences in
      plasma concentrations from 20 minutes to 6 hours after the dosing nor in
      pharmacokinetic parameters of triazolam between the EM and PM groups. No
      significant difference was found in psychomotor function between the EM and PM
      groups. These results suggest that CYP2C19 is not involved in the metabolism of
      triazolam and that CYP2C19 status is not a pharmacodynamic determinant of this
      triazolobenzodiazepine.

PMID- 9263375
TI  - Simple bioequivalence criteria: are they relevant to critical dose drugs?
      Experience gained from cyclosporine.
AB  - A critique of the current bioequivalence regulations is presented with reference
      to critical dose drugs. Using the development of a new cyclosporine formulation
      as an example, the deficiencies in current bioequivalence testing guidelines are
      examined and discussed. Based on the experience gained with cyclosporine,
      recommendations are made on how therapeutic equivalence, rather than just
      bioequivalence, should be established.

PMID- 9263376
TI  - Pharmacokinetics of mercaptopurine: plasma drug and red cell metabolite
      concentrations after an oral dose.
AB  - Measurement of red cell 6-mercaptopurine (MP) derived 6-thioguanine nucleotide
      (TGN) and methylmercaptopurine metabolites (MeMPs) can be used to monitor therapy
      in children who are administered MP for childhood lymphoblastic leukemia. Red
      cell TGNs are not influenced by the time of blood sampling in relation to the
      last MP dose. The purpose of this study was to find out whether the same is true
      for the MeMPs. Plasma MP and red cell MP metabolite pharmacokinetics were studied
      in seven children immediately before and for 4 hours after a protocol
      standardized dose of MP. Duplicate blood samples were taken, one was processed
      immediately whereas one was left at an ambient temperature for 24 hours. The
      variation in TGN and MeMP metabolites over the 0- to 4-hour period (10 time
      points per child) was within the error of the assays used. The coefficients of
      variation for the TGNs ranged from 2.7% to 7% and for the MeMPs, 4% to 10.7%.
      There was no difference in the TGN and MeMP concentrations measured when the
      blood samples were left for 24 hours. If a child takes a MP tablet immediately
      before a clinic appointment, it has no major influence on MeMP measurements.

PMID- 9263377
TI  - A case report on drug screening of nail clippings to detect prenatal drug
      exposure.
AB  - In a case of a sudden infant death syndrome-related death of a 3-month-old
      infant, nail clippings were positive for cocaine by gas chromatography-mass
      spectroscopy analysis that revealed a prenatal exposure to the drug substance. In
      utero exposure to drugs has been investigated using amniotic fluid, neonatal
      urine, meconium, and hair samples. Nail analysis offers some advantage over hair
      analysis because of its continuous growth and persistence after delivery. Nail
      material is easy to sample in suitable amounts. Currently, the cocaine finding
      cannot be related to the underlying cause of death. However, this observation
      indicates that nail analysis may be a new and valuable tool to screen newborns
      for intrauterine drug exposure. In addition, it can help collect information on
      the prevalence of possible embryotoxic effects and the link to postnatal
      manifestations of different dysfunctions in infants who are born by drug abusing
      mothers.

PMID- 9263378
TI  - Pharmacokinetic monitoring of anticancer drugs at King Faisal Specialist
      Hospital, Riyadh, Saudi Arabia.
AB  - Pharmacokinetic monitoring of anticancer agents has the potential to become of
      considerable clinical value. Recognizing this and the leading role of the King
      Faisal Specialist Hospital and Research Centre (KFSH & RC) in healthcare delivery
      in the Kingdom of Saudi Arabia, particularly in oncology, the authors have
      established a pharmacokinetics service and research laboratory equipped with the
      state-of-the-art analytical instrumentation. After the acquisition of these
      instruments, we initiated research work that lead to the development of improved
      analytical methods for methotrexate and 7-OH methotrexate (high-performance
      liquid chromatography [HPLC]), doxorubicin (HPLC), etoposide (HPLC), 5
      fluorouracil (HPLC), mitoxantrone (HPLC), mesna and dimesna (HPLC), taxol (HPLC),
      aminoglutethimide (HPLC), tamoxifen (HPLC), and acrolein (HPLC), cisplatin or
      carboplatin (electrothermal atomic absorption spectrophotometry, ETAAS),
      cyclophosphamide (gas chromatography) and CCNU and BCNU (gas chromatography).
      Currently, most of these drugs are monitored selectively as requested by
      oncologists at the KFSH & RC. The authors are aware that controlled, randomized
      studies of the concentration-effect relationships for many of these drugs are
      still missing. However, the authors hope that once these studies become
      available, this service will be used more fully.

PMID- 9263379
TI  - Changes in body weight with chronic, high-dose gabapentin therapy.
AB  - The authors reviewed changes in body weight in 44 patients treated with
      Gabapentin (GPN) for a period of 12 or more months. All patients had a seizure
      disorder and the dose of GPN was increased aiming at complete seizure control or
      until side effects limited further increase. Twenty-eight patients were receiving
      GPN dosages of > 3000 mg/day. Observed changes in body weight were as follows 10
      patients gained more than 10% of their baseline weight, 15 patients gained 5% to
      10% of baseline, 16 patients had no change, and 3 patients lost 5% to 10% of
      their initial weight. Weight increase started between the second and the third
      months of GPN treatment in most patients and tended to stabilize after 6 to 9
      months of treatment, although the doses of GPN remained unchanged. Weight gain
      occurred in patients taking GPN in combination with each of the major
      antiepileptic drugs including Felbatol and also occurred with GPN monotherapy.

PMID- 9263380
TI  - Kinetics and dynamics of single oral doses of sirolimus in sixteen renal
      transplant recipients.
AB  - Sirolimus is a new immunosuppressive drug that has been evaluated in animal
      experiments. The current study was conducted on humans with reformulated
      sirolimus in doses from 3 mg/m2 to 15 mg/m2. Sixteen renal transplant recipients
      were included in this phase I study to determine the safety, tolerance, and
      preliminary pharmacokinetics of increasing single doses of orally administered
      sirolimus. All 16 patients had stable renal graft function after a renal
      transplant at least 6 months before the study. Basal immunosuppression consisted
      of cyclosporine and prednisolone (n = 10) or cyclosporine, azathioprine, and
      prednisolone (n = 6). Four groups (I, 3 mg/m2; II, 5 mg/m2; III, 10 mg/m2; IV, 15
      mg/m2) of four patients were assigned randomly to receive sirolimus (n = 3) or
      placebo (n = 1). Among the 12 patients who received sirolimus, five had mild
      transient study events such as headache, nausea, mild dizziness, hypoglycemia,
      epistaxis, and decrease in platelets. No serious adverse events occurred and no
      nephrotoxic effects could be related to the single dose administration of
      sirolimus. The only study event that was judged as probably related to sirolimus
      was the single case of thrombocytopenia. The other events were evaluated as
      possibly related. Thrombocytopenia occurred at the highest dose level (15 mg/m2
      sirolimus). In two of the patients in the placebo group, slight elevations of
      liver enzymes and serum amylase were seen. Blood and plasma sirolimus
      concentrations were analyzed by an electrospray-high performance liquid/mass
      spectrophotometric (ESP-HPLC/MS) method Sirolimus showed an extensive red blood
      cell distribution with a mean blood/ plasma ratio of 49.1. The elimination half
      life ranged from 43.8 to 86.5 hours (mean 56.9 hours). The Cmax and the area
      under the concentration versus time curves (AUC) correlated reasonably with doses
      from 3 to 15 mg/m2. The oral dose clearance ranged from 42 to 339 ml/h.kg. No
      clinically significant differences were seen in the trough concentrations of
      cyclosporine or the AUCs before and after the administration of sirolimus.
      Administration of single oral doses of sirolimus from 3 to 15 mg/m2 was safe and
      well tolerated in stable renal transplant recipients. Thrombocytopenia may be the
      dose-limiting toxicity. Additional phase II and phase III clinical trials will
      define the immunosuppressive efficacy of sirolimus.

PMID- 9263381
TI  - Clinical outcome of smoking-cessation trial of nicotine chewing gum evaluated by
      analysis of nicotine in hair.
AB  - The axial distribution of nicotine along the hair shafts was examined in 21
      subjects enrolled in a placebo-controlled, double-blind trial of nicotine chewing
      gum (Nicorette) for validating their self-reported smoking behavior and their
      physicians' assessments. Hair samples obtained from the subjects once during the
      3-month follow-up period (n = 10 for placebo and n = 11 for Nicorette ad libitum)
      were analyzed for the cm x cm distribution of nicotine along the hair shafts.
      Hair analysis results were compared with the monthly self-reports and with the
      plasma concentrations of thiocyanate (SCN-) measured at 1-month intervals. A
      gradual decrease in nicotine content along the hair shafts generally corresponded
      to the decrease in self-reported number of cigarettes smoked daily by the
      subjects who reported that they abstained from smoking or decreased the number of
      daily cigarettes in placebo and nicotine chewing gum groups. Because nicotine may
      dissociate slowly from hair follicle cells, nicotine in the hair did not mark a
      sudden decrease or cessation of smoking and, therefore, hair analysis tended to
      underestimate the real decrease of smoking. However, physician assessment seemed
      to depend solely on self-reporting because the time profile of changes in serum
      SCN- concentration did not correspond necessarily to the changes in the self
      reported number of cigarettes used daily.

PMID- 9263382
TI  - A limited sampling approach in bioequivalence studies.
AB  - A limited sampling model (LSM) has been developed for an antidepressant immediate
      release product (Drug A) and an antiepileptic controlled release product (Drug B)
      to predict the area under the curve (AUC) and the maximum plasma concentration
      (Cmax) and to compare the bioequivalence of two formulations of each drug using
      predicted versus observed AUC and Cmax after a single oral dose. The LSM for drug
      A was developed using data from 10 healthy people. The correlation between plasma
      concentration (independent variable) at selected time points with the AUC or Cmax
      (dependent variable) was evaluated by simple regression analysis. The linear
      regression that gave the best correlation coefficient (r) for a single sampling
      time versus AUC or Cmax was chosen as the LSM. The model provided good estimates
      of AUC and Cmax for drug A. The 90% confidence interval on log transformed
      observed and predicted AUC and Cmax were as follows: AUC observed = 100% to 118%,
      AUC predicted = 101% to 117%, Cmax observed = 99% to 125%, and Cmax predicted =
      100% to 131%. The LSM for drug B was developed using a similar approach to drug
      A. The 90% confidence interval on log transformed observed and predicted AUC and
      Cmax were: AUC observed = 99% to 110%, AUC predicted = 99% to 118%, Cmax observed
      = 107% to 120%, and Cmax predicted = 99% to 111%. Although the predicted Cmax did
      not meet the 90% confidence interval for drug A, the method described here may be
      used to estimate AUC and Cmax for a drug in bioequivalence studies without
      detailed blood sampling. More research is needed in this direction.

PMID- 9263383
TI  - Comparison by external quality assessment of performance of analytical systems
      for measurement of therapeutic drugs in serum.
AB  - The precision and accuracy of analytical methods currently in use for therapeutic
      drug monitoring were evaluated from proficiency test data provided by
      laboratories participating in the international Healthcontrol external quality
      assessment scheme for a range of eight antiepileptic drugs, theophylline,
      caffeine, and digoxin. Different analytical systems were assessed after grouping
      according to the reagent source and the analyzer used. The majority of analytical
      methods produced comparable levels of performance with coefficient of variation
      of < 10% and accuracy within +/-7% of the spike value. Emit reagents were
      implemented successfully on diverse analyzers but data from the Cobas Mira were
      generally in the technique group with significantly lower precision. Bias
      problems were evident for a number of FPIA assays for specific drugs. For
      example, caffeine interference was present in theophylline measurements by Sigma
      FPIA reagents whereas use of nonhuman matrix caused a negative bias in Abbott
      FPIA measurements of carbamazepine. Measurements in the group with highest
      positive bias were produced by Roche FPIA reagents for phenytoin, phenobarbitone,
      and carbamazepine. Chromatographic and turbidimetric techniques performed
      satisfactorily. The variable performance of the different reagent/analyzer
      combinations demonstrates the value of the narrower technique classification in
      the assessment of assay performance.

PMID- 9263384
TI  - Effect of drugs and cocaine metabolites on cocaine and cocaethylene binding to
      human serum in vitro.
AB  - The effect of amphetamine (AMPH), codeine (COD), methamphetamine (MEPH), morphine
      (MORP), and benzoylecgonine (BE) on the binding of cocaethylene (CE) and cocaine
      (COC) to human serum in vitro was investigated by equilibrium dialysis at 4
      degrees C. Each compound was added individually at concentrations of 500, 1,000,
      or 2,000 nM to pooled human serum containing COC or CE at 500 nM concentration.
      For COC, the addition of COD, MEPH, and CE enhanced serum binding whereas MORP
      and BE decreased it. Variable effects on COC binding were noted for AMPH. For CE,
      the addition of COD and COC generally increased binding whereas MORP decreased
      it. No appreciable effect on CE binding was observed after adding AMPH, MEPH, and
      BE. Except for CE, AMPH, and MEPH in the presence of COC, the binding of COC and
      CE tended to be less with 2,000 nM of each added drug than at lower
      concentrations of them, presumably because of mass-action displacement of COC and
      CE at the higher concentration. These findings should be clinically important
      because these drugs are frequently found together in patients.

PMID- 9263385
TI  - A rapid cost-effective high-performance liquid chromatographic (HPLC) assay of
      serum lamotrigine after liquid-liquid extraction and using HPLC conditions
      routinely used for analysis of barbiturates.
AB  - Lamotrigine (lamictal) is a new anticonvulsant drug approved by the FDA for
      clinical use. Therapeutic monitoring of lamotrigine is useful for patient
      management and avoidance of toxicity. The suggested therapeutic range is 1 to 4
      micrograms/ml. The authors describe a simple high-performance liquid
      chromatographic (HPLC) method for analysis of lamotrigine from serum. Serum (0.5
      ml) was alkalinized with borate buffer (pH 9.8). Lamotrigine and the internal
      standard thiopental were extracted with 10 ml of chloroform. After evaporation of
      the extract, the residue was reconstituted in the mobile phase (prepared by
      mixing 750 ml of potassium dihydrogen phosphate, 550 ml of deionized water, 430
      ml of methanol, and 100 microliters of triethylamine as an ion pairing reagent)
      and injected into an LC-18 column (15 cm x 4.6 mm). The authors use this HPLC
      system routinely in their laboratory for the analysis of barbiturates. They
      demonstrated that the same system can be used for the analysis of lamotrigine.
      The within-run and between-run precisions of the lamotrigine assay were 1.63%
      (mean = 3.05, SD = 0.05 microgram/ml, n = 6) and 3.7% (mean = 2.97 micrograms/ml,
      SD = 0.11, n = 8). The assay was linear for serum lamotrigine concentrations of
      0.5 microgram/ml to 20 micrograms/ml with a detection limit of 0.5 microgram/ml.
      The authors observed excellent correlation between serum lamotrigine
      concentrations measured by their assay and a reference laboratory in six patients
      receiving lamotrigine. Their assay is free from interferences from common
      tricyclic antidepressants, benzodiazepines, other common anticonvulsants,
      salicylate, and acetaminophen.

PMID- 9263386
TI  - Ketoconazole and fluconazole inhibition of the metabolism of cyclosporin A by
      human liver in vitro.
AB  - The effects of the important antifungal agents, ketoconazole (Ket) and
      fluconazole (Flu), on the microsomal metabolism of cyclosporin A (CsA) by seven
      human livers was measured in vitro. A total of eight CsA metabolites were
      identified by high-performance liquid chromatography, with metabolites AM9 and
      AM1 predominating. Ket was a stronger inhibitor than Flu for the formation of
      each of the 8 metabolites; the mean IC50 for the inhibition of total CsA
      metabolism was 0.26 +/- 0.08 microM and 85.7 +/- 23.9 microM for Ket and Flu,
      respectively. Inhibition by Ket and Flu was noncompetitive, with Ki = 0.13 microM
      and 25.1 microM, respectively. There was considerable interindividual variation
      in the sensitivity of CsA metabolism to inhibition by Ket or Flu and the degree
      of inhibition was not uniform across the range of individual CsA metabolites. In
      six of the seven livers tested, Ket and Flu inhibited the aggregate formation of
      secondary metabolites (AM19, AM49, AM4N9, and AM1c) more than the aggregate
      formation of primary metabolites (AM9, AM1, and AM4N) and inhibited the formation
      of AM9 more than AM1. Although the degree of inhibition of total CsA metabolism
      by Flu correlated directly with the control (uninhibited) rate of total CsA
      metabolism (r = 0.95), no similar correlation for inhibition by Ket was noted,
      nor was the magnitude of inhibition by Ket and Flu related. The results are
      discussed in relation to the inhibition of CsA metabolism by Ket and Flu in
      patients in vivo and to the possibility of changes in the efficacy and toxicity
      of CsA as a result of alterations in its metabolite profile.

PMID- 9263387
TI  - Comparison of cyclophilin binding assay and radioimmunoassay in monitoring of
      blood cyclosporine.
AB  - Cyclosporine binds with cyclophilin, an abundant protein found in almost all
      tissues, and the resulting complex interacts with calcineurin diminishing T-cell
      activation. Cyclophilin can be regarded as a cellular "receptor" for
      cyclosporine. Measuring cyclosporine binding to cyclophilin may offer a link
      between pharmacokinetics and pharmacodynamics that could improve monitoring of
      cyclosporine therapy. The authors investigated the feasibility of the cyclophilin
      binding assay and compared the results with a standard specific monoclonal
      radioimmunoassay in 100 blood samples taken for therapeutic drug monitoring. The
      results obtained with these methods were related closely with each other (r =
      0.96; p < 0.001) but the mean (+/-SEM) concentrations were approximately two-fold
      higher in cyclophilin binding assay than in radioimmunoassay (520.4 +/- 49.9
      ng/ml versus 257.7 +/- 28.6 ng/ml, respectively, p < 0.001). The shapes of the
      cyclosporine concentration versus time curves in two patients after a liver and
      heart transplantation, respectively, were similar after both methods but
      cyclophilin binding assay gave higher values than radioimmunoassay. Before firm
      conclusions on the clinical value of cyclophilin binding assay can be made,
      comparative studies in patients linking cyclosporine concentrations measured with
      cyclophilin binding assay and standard methods to the therapeutic outcome are
      needed.

PMID- 9263388
TI  - A population pharmacokinetic model of trimethoprim in patients with pneumocystis
      pneumonia, made with parametric and nonparametric methods.
AB  - A population pharmacokinetic model of intravenously and orally administered
      trimethoprim in patients with acquired immunodeficiency syndrome and Pneumocystis
      carinii pneumonia has been made using a parametric iterative two-stage Bayesian
      and a nonparametric expectation maximization computer program. When good
      information was present in the serum level data, both methods obtained similar
      results. With the nonparametric expectation maximization program, the median
      apparent rate constant for absorption (Ka) was 1.602 hr-1, median slope (Ks) of
      the relationship between creatinine clearance and elimination was 0.001168 hr-1,
      median apparent volume of distribution (Vs) was 1.058 l/kg, and median fraction
      of oral dose absorbed (Fa) was 0.955. These results permit dosage
      individualization adjusted to body weight and renal function to achieve chosen
      serum level peak and trough goals. Peak goals of 9 ug/ml and trough goals of 5
      ug/ml appear reasonable for most patients in this population, and should permit
      most to complete an effective course of therapy with a reduced risk for treatment
      terminating hematologic toxicity. However, therapeutic goals should always be
      selected based on each patient's apparent need for the drug and the risk of
      toxicity that is justifiably acceptable to obtain the expected benefits of the
      drug.

PMID- 9263389
TI  - Analysis of the antiepileptic phenyltriazine compound lamotrigine using gas
      chromatography with nitrogen phosphorus detection.
AB  - A method is described for the determination of lamotrigine in serum or plasma,
      based on gas chromatography with nitrogen-phosphorus detection. The method
      requires minimal sample preparation. The drug is extracted from 1.0 ml of serum
      at pH 11 into butylacetate containing prazepam as internal standard. An aliquot
      of the organic phase is then injected onto an HP-5 fused silica capillary column
      and analyzed with temperature programming from 90 degrees to 250 degrees C.
      Lamotrigine is characterized by a relative retention time of 0.832 (+/-0.03)
      compared with prazepam. The method is competitive with the reported high
      performance liquid chromatography procedures in terms of precision and
      sensitivity. Coefficients of variation, calculated from the results of between
      run reproducibility tests, were 6.7%, 4.6%, 4.8%, and 6.2% for samples spiked
      with 0.20, 1.21, 2.42 and 10.84 micrograms/ml lamotrigine, respectively. The
      lower limit of quantitation of the method is 0.15 microgram/ml. The proposed
      procedure can be integrated easily in a comprehensive toxicology screening.

PMID- 9263390
TI  - Interference of oleandrin and oleandrigenin in digitoxin immunoassays: minimal
      cross reactivity with a new monoclonal chemiluminescent assay and high cross
      reactivity with the fluorescence polarization assay.
AB  - Toxicity from ingestion of the oleander plant is common. Oleandrin, the oleander
      glycoside, has structural similarity to cardiac glycoside digoxin and is known to
      cross react with various digoxin immunoassays. The authors studied the cross
      reactivity of oleandrin and its deglycosylated congener oleandrigenin with a
      fluorescence polarization immunoassay for digitoxin and compared their results
      with a new chemiluminescent assay for digitoxin on the Automated Chemiluminescent
      System (ACS:180 Plus) from Chiron Diagnostics. Even though the chemiluminescent
      assay has been reported to be comparable with the fluorescence polarization assay
      among normal patient population, oleandrin and oleandrigenin showed very high
      cross reactivities with the fluorescence polarization immunoassay and minimal
      cross reactivity with the new chemiluminescent assay. When the authors
      supplemented a serum specimen containing no digitoxin with 50 micrograms/ml of
      oleandrin, the fluorescence polarization assay recorded a value of 535.7 ng/ml of
      digitoxin equivalent, whereas the new chemiluminescent assay recorded a value of
      10.3 ng/ml of digitoxin equivalent. The cross reactivity of oleandrigenin with
      the fluorescence polarization immunoassay for digitoxin was significantly lower
      than oleandrin. The presence of oleandrin also falsely elevated total digitoxin
      level in a specimen supplemented with digitoxin and oleandrin. The authors also
      measured free digitoxin concentration by the fluorescence polarization
      immunoassay in the ultrafiltrate of serum supplemented with digitoxin and
      oleandrin. Because digitoxin and oleandrin are bound strongly to protein,
      monitoring free digitoxin concentration by the fluorescence polarization
      immunoassay instead of total digitoxin concentration does not eliminate oleandrin
      interference. The authors conclude that fluorescence polarization immunoassay for
      digitoxin has a high cross reactivity with oleandrin and can falsely elevate
      digitoxin concentration in the presence of oleandrin, whereas the new
      chemiluminescent assay for digitoxin is almost free from interferences from
      oleandrin.

PMID- 9263391
TI  - A specific method for the measurement of tacrolimus in human whole blood by
      liquid chromatography/tandem mass spectrometry.
AB  - Tacrolimus (FK 506) measurement by immunoassays in clinical samples of organ
      transplant patients often lacks a specific reference method. A method combining
      liquid chromatography (LC) with tandem mass spectrometry (MS/MS) was developed to
      quantify tacrolimus in whole blood. Liquid-liquid extraction was performed on 1
      ml of sample before narrow-bore LC/MS/MS analysis. Ascomycin was used as an
      internal standard. The standard curve was composed of seven points ranging from 1
      to 50 micrograms/l (average r2 = 0.9999). Limits of detection and quantitation
      were 0.25 and 0.75 microgram/l, respectively. Imprecision was < 5% across the
      therapeutic range. Tacrolimus recovery averaged 62%. The most abundant
      metabolites detected in clinical samples were 13-O- and 15-O-demethyl tacrolimus.
      This method was used in a comparison study with a microparticle enzyme
      immunoassay (MEIA): MEIA = 1.03 LC/MS/MS -0.084 (microgram/l), (Sy/x = 1.43), r2
      = 0.933. With its high sensitivity and specificity, this LC/MS/MS method presents
      a good reference method for immunoassay evaluation as well as a valuable tool for
      metabolism studies.

PMID- 9263392
TI  - Heat treatment of human serum to inactivate HIV does not alter protein binding of
      selected drugs.
AB  - Human immunodeficiency virus (HIV) may be transmitted via certain biological
      fluids, particularly blood. To minimize the risk of accidental exposure, the
      virus may be inactivated by heat treatment of blood, plasma, or serum samples at
      54-56 degrees C for 5 h. The objective of this study was to determine whether
      heat treatment of human serum alters the protein binding of model compounds.
      Diazepam, phenytoin, and digitoxin were selected for investigation because they
      bind to three different sites on human serum albumin (HSA); propranolol also was
      examined since it binds to both HSA and alpha 1-acid glycoprotein. The unbound
      fraction of selected drugs was measured by ultrafiltration at 37 degrees C after
      addition of each compound to either untreated or heat-treated serum. The
      percentage unbound in serum for diazepam, phenytoin, digitoxin, and propranolol
      was not significantly different between the untreated and heat-treated samples.
      Therefore, heat treatment of serum does not appear to alter the binding
      characteristics at these four binding sites and would not be expected to lead to
      erroneous unbound concentration estimates and inappropriate adjustments in drug
      therapy.

PMID- 9263393
TI  - Automated determination of clozapine and major metabolites in serum and urine.
AB  - Clozapine is an atypical neuroleptic that is increasingly used for the treatment
      of schizophrenia. An automated method was developed for the routine
      quantification of clozapine and its major metabolites, N-desmethylclozapine and
      clozapine N-oxide, in human serum and urine by column switching and online high
      performance liquid chromatography with ultraviolet detection. The method included
      adsorption of clozapine and its metabolites on a cyanopropyl-coated clean-up
      column (10 microns; 10 mm x 4.0 mm ID), washing interfering serum constituents to
      waste by deionized water, and, after column switching, separation on C18 ODS
      Hypersil reversed-phase material (5 microns; 250 mm x 4.6 mm ID). The compounds
      of interest were separated and eluted in fewer than 20 minutes, using a mobile
      phase consisting of 37.5 acetonitril:62.5 water, containing 0.4% (vol/vol)
      tetramethylethylenediamine and adjusted to pH 6.5 with concentrated acetic acid.
      Ultraviolet-detection was performed at 254 nm. The determinations exhibited
      linearity between detector signal and drug concentrations in a range from 5 ng/ml
      to 50 micrograms/ml. As little as 10 ng/ml of clozapine and 20 or 30 ng/ml of the
      metabolites was quantifiable. Interferences with other psychotropic drugs, serum,
      or urine constituents were negligible. The automated procedure enables the
      analysis of clozapine and metabolites in serum or urine in less than 1 hour.

PMID- 9263394
TI  - cDNA cloning of a heterogeneous two-chain anticoagulant protein IX-bp.
AB  - IX-bp and IX/X-bp are heterogeneous two-chain anticoagulant proteins isolated
      from the venom of habu snake, Trimeresurus flavoviridis. The amino acid sequence
      of one (B chain) of their two chains is identical. We recently reported the
      cloning of cDNA encoding the B chain and that of the A chain of IX/X-bp. Here, we
      report the isolation and characterization of cDNA clones encoding the A chain of
      IX-bp. The 697-bp sequence showed a putative ORF capable of encoding a 152-amino
      acid protein containing a 23-amino-acid signal peptide. The overall amino acid
      sequence identity between the pre-A chain of IX-bp and that of IX/X-bp is 84%,
      whereas the cDNA sequence identity of the two ORFs is 91% indicating that habu
      snake acquired the variety of venom proteins by efficient mutations of antonymous
      sites.

PMID- 9263395
TI  - Alterations in the free radical generation and nitric oxide release from rat
      peripheral polymorphonuclear leukocytes following thrombosis.
AB  - The present investigation was undertaken to study the alterations in free radical
      generation and release of nitric oxide (NO) from polymorphonuclear leukocytes
      (PMNLs) following thrombosis. Thrombosis was induced in rats by intravenous
      injection of collagen and adrenaline. PMNLs were separated from rat blood by
      using dextran sedimentation and Ficoll-Hypaque. Arachidonic acid (AA), formyl
      methionine leucine phenylalanine (FMLP) and opsonized zymosan (OZ) induced free
      radical generation was estimated as luminol (LCL) and Lucigenin (LUCDCL)
      dependent chemiluminescence. PMNLs nitric oxide synthase (NOS) activity and NO
      release were measured by using [14C] L-Arginine (L-Arg) and oxy-hemoglobin
      respectively. LCL and LUCDCL responses in rat PMNLs were significantly attenuated
      following thrombosis. There was no change in the release of myeloperoxidase
      enzyme (MPO) from PMNLs obtained following thrombosis. PMNLs NOS activity and NO
      release were also found to be increased after thrombosis. Pretreatment of rat
      PMNLs with 10 mM L-NAME (NO precursor) or 100 microM sodium nitroprusside (NO
      donor), resulted in significant reduction of AA induced LCL response. Results
      obtained indicate that NO release form PMNLs was augmented while free radical
      generation response was attenuated after the induction of thrombosis.

PMID- 9263396
TI  - Chimeric fibrolase: covalent attachment of an RGD-like peptide to create a
      potentially more effective thrombolytic agent.
AB  - We have prepared an agent possessing both thrombolytic and antiplatelet
      properties, by conjugating fibrolase, a direct-acting fibrinolytic enzyme
      isolated from southern copperhead venom, to a peptide which inhibits platelet
      aggregation. Heterobifunctional coupling reagents, N-succinimidyl 3-(2
      pyridyldithio) propionate (SPDP) or sulfosuccinimidyl 6-[alpha-methyl-alpha-(2
      pyridyldithio)-toluamido]hexanoate (Sulfo-LC-SMPT), were used in a molar ratio of
      10:1 (coupling agent/fibrolase). The N-hydroxy-succinimide of the coupling agent
      reacts with surface epsilon-amino groups of lysine residues on fibrolase and
      provides a dithio group that is highly reactive with small thiol compounds. The
      derivatives obtained in the first reaction contain approximately two moles of 2
      pyridyl disulphide per mole of enzyme. These derivatives were then reacted with
      the free thiol group in an antiplatelet peptide at a molar ratio of 2:1
      (peptide/fibrolase). The peptide-fibrolase conjugate was purified by cation
      exchange HPLC and analyzed by amino acid analysis. The conjugate contains one
      mole peptide per mole of fibrolase and retains approximately 85% fibrinolytic
      activity. The IC50 for inhibition of platelet aggregation in human PRP is 300 nM
      for the conjugate and 67 nM for the antiplatelet peptide. These results
      demonstrate the successful formation of a novel chimeric protein with
      bifunctional activity.

PMID- 9263398
TI  - Inhibition of leukocyte leukotriene B4 production by an olive oil-derived phenol
      identified by mass-spectrometry.
AB  - We have evaluated the effects of hydroxytyrosol (HT), a potent antioxidant
      present in olive oil, on the formation of arachidonic acid 5-lipoxygenase
      metabolites by leukocytes in vitro. HT, a simple phenolic compound, extracted
      from first-pressure oil, was isolated by HPLC and characterized by gas
      chromatography/mass spectrometry. HT inhibited in a dose-related manner the
      production of leukotriene B4 (LTB4) by calcium ionophore-stimulated leukocytes.
      As expected, similar inhibition was observed for omega-oxidized metabolites of
      LTB4, namely 20-hydroxy and 20-carboxy-LTB4. The results disclose a new
      biological activity of olive oil-derived phenols on leukocyte eicosanoid
      production.

PMID- 9263397
TI  - Quantitative PCR analysis reveals novel expression of prothrombin mRNA and
      regulation of its levels in developing mouse muscle.
AB  - Precise determination of mRNA levels is an essential element in any investigation
      of complex regulatory systems. Classical methodologies such as Northern
      hybridization suffer from requirements for significant samples of material and
      also a degree of nonspecificity. Recently, quantitative techniques involving PCR
      amplification have been devised. We have developed and applied such procedures to
      the determination of prothrombin messages in skeletal muscle cells during
      development. In addition to its role in the blood coagulation cascade, the serine
      protease thrombin has been shown to participate in several signaling events in
      the neuromuscular system. The inactive precursor, prothrombin, primarily produced
      in the liver, has also been shown to be synthesized and developmentally-regulated
      in the brain. In skeletal muscle, thrombin is a mediator of activity-dependent
      polyneuronal synapse elimination (ADPSE) which occurs in early postnatal
      development. Recent experiments showing that thrombin is released from myotubes
      in culture under the influence of acetylcholine suggest that locally-synthesized
      prothrombin may be the source of this Hebbian synaptic interaction. We have
      determined that prothrombin is expressed in skeletal muscle, as the likely source
      of thrombin involved in ADPSE, and the current results show the quantitative
      expression of muscle prothrombin during this time of intense synapse remodeling.

PMID- 9263399
TI  - Bactericidal/permeability-increasing protein ameliorates hypercoagulability after
      hemorrhagic shock.
AB  - We recently showed that both plasminogen activator inhibitor-1 (PAI-1) and tissue
      factor (TF) are induced after a massive hemorrhage. In this study, we determined
      if bactericidal/permeability-increasing protein (BPI) has any effects on the
      induction of these factors after hemorrhagic shock. Three days after cannulation,
      rats were bled and maintained at a mean blood pressure of 40 mmHg for 60 min, and
      then were resuscitated with the shed blood and an equal volume of saline over 60
      min. Rats in the BPI group were given at 6 mg/kg of rBPI21 (XOMA, Berkeley, CA; a
      3-mg/kg dose at the beginning of hemorrhage followed by two doses of 1.5 mg/kg at
      the end of shock and at the end of resuscitation). The control group was treated
      similarly to the BPI group, but received control protein in the same dose as
      rBPI21. Plasma endotoxin concentration, whole blood clotting time (WBCT) and
      plasma PAI activity were measured at times 0, 2, 4, 6, and 8 h. The time-course
      changes in mRNA of TF, PAI-1, tumor necrosis factor alpha (TNF alpha),
      interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) were also detected in
      the liver by reverse transcription and polymerase chain reaction. The plasma
      endotoxin levels increased after hemorrhagic shock and showed a peak at 2 h in
      the control group. These increases were significantly neutralized by rBPI21
      treatment at 2 h in the BPI group. WBCT decreased and PAI activity increased
      rapidly after hemorrhagic shock in the control group. These changes were
      significantly smaller in the BPI group at 6 and 8 h. The increases in mRNA of TF,
      PAI-1, TNF alpha, and IL-6 were also attenuated by rBPI21 treatment. These
      results show that BPI ameliorates hypercoagulability after hemorrhagic shock and
      suggest that endotoxin plays a role in the pathogenesis of thrombogenic responses
      after hemorrhagic shock.

PMID- 9263400
TI  - Sphingosine stimulates thrombin-induced gelation of the fibrinogen.

PMID- 9263402
TI  - Illuminating the force: bacterial mitosis?

PMID- 9263401
TI  - Contact system in healthy term newborns: reference values in cord blood.

PMID- 9263403
TI  - Something in the air: volatile signals in plant defence.

PMID- 9263404
TI  - Control of HIV co-receptor expression: implications for pathogenesis and
      treatment.

PMID- 9263405
TI  - Evolution in health and disease.

PMID- 9263406
TI  - The chlamydial inclusion membrane as an engine of survival.

PMID- 9263407
TI  - Herpes simplex virus and the cytoskeleton.

PMID- 9263408
TI  - Natural functions of bacterial multidrug transporters.
AB  - Bacteria express several multidrug transporters that recognize structurally
      dissimilar toxic molecules and expel them from cells. These transporters may have
      evolved to protect bacteria from diverse environmental toxins or to transport
      specific physiological compounds with the ability to expel drugs being only a
      fortuitous side effect.

PMID- 9263409
TI  - Endogenous retroviruses and the evolution of resistance to retroviral infection.
AB  - The current AIDS epidemic has rekindled interest in the evolution of retroviruses
      and the development of resistance to infection. Retroviruses and their vertebrate
      hosts have coexisted for millions of years, during which time a variety of host
      defence mechanisms has evolved. One repeated strategy is to use endogenous
      retroviruses to combat infection by their exogenous relatives.

PMID- 9263410
TI  - The record of horizontal gene transfer in Salmonella.
AB  - The evolution of virulence in Salmonella is driven by horizontal gene transfer.
      This has given rise to highly flexible pathogens that are able to colonize new
      niches and extend their host range. Tracing the record of horizontal gene
      transfer can provide clues to the virulence factors that contribute to the
      formation of new pathovars.

PMID- 9263411
TI  - DNA supercoiling and bacterial adaptation: thermotolerance and thermoresistance.
AB  - When bacterial cells are shifted to higher temperatures their degree of DNA
      supercoiling changes. Topoisomerases are involved in bacterial adaptation to
      environmental changes requiring rapid shifts in gene expression. This role in
      heat shock has been elucidated by genetic studies on the Escherichia coli topA
      gene and its sigma 32-dependent promoter, P1. Other studies have shown that
      certain gyrA mutants have increased thermoresistance.

PMID- 9263412
TI  - Influence of microbial infections on the progression of HIV disease.
AB  - HIV infection is associated with immune activation, which in turn stimulates HIV
      replication. Certain other co-infections cause immune activation and may
      contribute to an increased viral load. The impact of co-infections by
      microorganisms such as Mycobacterium tuberculosis can be important for patient
      survival, particularly those at high risk of exposure to infection and with poor
      access to medical care.

PMID- 9263413
TI  - PrP genetics in sheep and the applications for scrapie and BSE.
AB  - The strong links between PrP genotype and the occurrence of scrapie in sheep
      strengthen evidence supporting the central importance of the PrP protein in the
      development of transmissible spongiform encephalopathies, despite the fact that
      the cattle PrP gene has, so far, failed to show any association between PrP
      alleles and susceptibility to BSE.

PMID- 9263414
TI  - Prenatal ultrasound examinations: for whom, by whom, what, when and how many?

PMID- 9263415
TI  - Classical versus artificial neural network analysis.

PMID- 9263416
TI  - Doppler indices in tumors--resolution of a dilemma?

PMID- 9263418
TI  - Fetal pyelectasis in consecutive pregnancies: a possible genetic predisposition.
AB  - Mild fetal pyelectasis is a relatively common finding. The objective of this
      study was to assess its recurrence rate in subsequent pregnancies. The study
      comprised 420 women with two consecutive normal uncomplicated pregnancies
      screened at 15-24 weeks' gestation by ultrasound. Pyelectasis was defined as a
      fetal pelvis of 4 mm or more in its anterior-posterior dimensions. Of 64 fetuses
      with pyelectasis, 43 (67%) had a recurrence of this finding in their subsequent
      pregnancy. Compared with normal fetuses, those with pyelectasis had a relative
      risk of 6.1 to have a recurrence of this finding in their next pregnancy (95%
      confidence interval, 4.3-7.5, p < 0.001). These results suggest a predisposition
      for pyelectusis that may be influenced by genetic and/or environmental factors.
      More data are needed before an accurate adjustment based on previous results can
      be made.

PMID- 9263417
TI  - Mild pyelectasis ascertained with prenatal ultrasonography is pediatrically
      significant.
AB  - Isolated 'mild renal collecting system dilatation' (mild pyelectasis) is a common
      prenatal sonographic finding. An association between mild pyelectasis and fetal
      aneuploidy has been established, but in the absence of a concomitant anomaly,
      mild pyelectasis is usually regarded as benign and of no clinical consequence,
      and follow-up is often not obtained after the initial ascertainment. To test
      this, we investigated the relationship between mild pyelectasis and (1)
      progression to hydronephrosis; (2) postnatal vesicoureteral reflux (VUR); and (3)
      postnatal surgery. Between 1 January 1992 and 1 January 1995, we performed 453
      prenatal sonographic examinations of 306 patients with mild fetal pyelectasis and
      no other anomalies. During the course of a routine sonographic examination, we
      performed a detailed evaluation of the fetal genitourinary tract, Mild
      pyelectasis was defined as a pelvocalyceal fluid-filled space with the smallest
      of two transverse perpendicular sonographic measurements of > or = 4 mm and < 10
      mm. Hydronephrosis was defined similarly, but with a measurement of > or = 10 mm.
      Postnatal urological assessment was obtained with routine renal ultrasonography,
      and voiding cystourethrography (VCUG), measurement of 99mTc-labelled
      diethylenetriamine pentaacetic acid (DPTA) mercaptacetyltriglycerine (MAG3), and
      intravenous pyelogram, as necessary. After exclusion criteria were applied, 294
      (96%) patients with isolated fetal pyelectasis were considered. A total of 251
      (82%) of these were followed with ultrasonography prenatally and during the
      postnatal period. Two or more prenatal examinations were carried out in 129
      patients (51%) and in 35 (27%) of these cases the biometry progressed to frank
      hydronephrosis (> 10 mm). In only six (5%) of the cases followed prenatally did
      the measurement diminish to < 4 mm. We found a greater variability in prenatal
      renal biometry throughout gestation in infants found to have VUR, when compared
      with those who had no VUR. On postnatal follow-up, 84 patients had VCUG. Sixteen
      of these patients (6% of all patients [16/251] and 19% [16/84] of those who had
      the test) were found to have an abnormal finding. Whereas the prenatal appearance
      of mild pyelectasis improved in only a small number of cases, we found that it
      progressed to hydronephrosis in 27% of cases. Postnatal evaluation found VUR to
      be common in apparent uncomplicated mild prenatal pyelectasis. Although postnatal
      surgery was necessary in only a small number of cases, surgical intervention was
      necessary in 33% (four of 12) of those with VUR.

PMID- 9263419
TI  - A cross-sectional study of changes in fetal renal size with gestation in
      appropriate- and small-for-gestational-age fetuses.
AB  - This cross-sectional study aimed to determine whether there are differences in
      kidney size and shape in small- and appropriate-for-gestational-age fetuses at
      different gestations. In the Fetal Growth Clinic of a large university hospital
      in England, 219 singleton fetuses were studied cross-sectionally at different
      gestational ages from 22 to 38 weeks. At each gestational age, the fetal kidney
      length, circumference and anterior-posterior and transverse diameters were
      measured using an Aloka 650 SL machine. At birth, the fetuses were classified as
      small or appropriate for gestational age, depending on the birth weight centile;
      the various kidney measurements for the two groups were compared. The kidney
      lengths at different gestational ages were similar in the two groups. The
      circumference and transverse and anterior-posterior diameters were significantly
      greater in the appropriate-for-gestational-age fetuses from about 28 weeks'
      gestation. We conclude that differences in fetal kidney size with gestation
      manifest from as early as 26-28 weeks. The differentially smaller anterior
      posterior and transverse kidney diameters in small-for-gestational age fetuses,
      resulted in altered renal morphology, producing sausage-shaped kidneys.

PMID- 9263420
TI  - Pulmonary venous blood flow in the human fetus.
AB  - The objective of this study was to assess the feasibility of recording pulmonary
      venous blood flow in the human fetus, and to evaluate its relationship with
      gestational age. We studied 152 singleton pregnancies between the 19th and 40th
      weeks of gestation. One hundred and one cases were studied cross-sectionally to
      gather data on color flow visualization, and 51 were studied longitudinally. The
      upper right pulmonary vein was interrogated by pulsed wave Doppler to assess
      pulmonary venous blood flow. On color Doppler, the upper right pulmonary vein
      could be imaged in 89.6% of cases in the peri-atrial tract and in 75% of cases
      within the lung. The upper left pulmonary vein could only be imaged in 8% of
      cases close to the atrium and in 41% of cases within the lung. Reliable velocity
      waveforms were obtained in 91% of cases. The mean systolic peak velocity was
      22.19 +/- 6.39 cm/s and the mean diastolic peak velocity was 22.1 +/- 6.35 cm/s.
      Both increased significantly with gestational age. Reversed end-diastolic blood
      flow was present in 18% of cases, regardless of gestational age and fetal heart
      rate. Expressed as a percentage of the forward flow velocity time integral, its
      value was 7.65 +/- 5.2%. Our data seem to confirm the presence of pulsatile
      pulmonary venous blood flow in the second- and third-trimester fetus. Normative
      data have been established for the second and third trimesters of pregnancy.

PMID- 9263421
TI  - Venous blood flow pattern suggesting tachycardia-induced 'cardiomyopathy' in the
      fetus.
AB  - Studies in the fetal lamb and human fetus demonstrated that, in the late stage of
      supraventricular tachycardia, myocardial dysfunction (tachycardia-induced
      'cardiomyopathy') may appear and even persist after drug-induced conversion to
      sinus rhythm. The objective of this study was to verify whether these changes in
      cardiac function are reflected in the venous system. In seven fetuses with
      supraventricular tachycardia (five with hydrops and four of these with
      atrioventricular valve incompetence during tachycardia) between 24 and 33 weeks
      of gestation, spectral Doppler analysis of flow velocity waveforms in the
      inferior vena cava and the ductus venosus was performed before and after drug
      induced cardioversion, and was compared with reference values known from the
      literature and our own indices obtained in 129 normal pregnancies. After drug
      induced conversion from supraventricular tachycardia to sinus rhythm associated
      with a change from a pulsatile to a normal biphasic forward venous blood flow
      pattern, abnormal venous indices resulting from increased reverse blood flow
      during atrial contraction persisted for 2-42 days (median 12 days). Severe
      functional tricuspid insufficiency can lead to a significant decrease in the
      systolic peak velocity with deterioration of the venous blood flow indices. In
      the first days after supraventricular tachycardia, rapid changes in these indices
      seem to depend predominantly on the decrease of tricuspid insufficiency and the
      increase of the systolic peak velocity. In addition to the persistence of
      atrioventricular valve regurgitation, abnormal indices of venous blood flow
      during sinus rhythm indicate the existence of altered myocardial function,
      suggesting reversible tachycardia-induced 'cardiomyopathy'. Blood flow indices in
      the venous system seem to reflect changing myocardial function very sensitively
      and rapidly and, therefore, appear very useful in the surveillance of the fetus
      with tachyarrhythmia under drug therapy, especially with regard to the assessment
      of cardiac function at the time of cardioversion and in the period after
      supraventricular tachycardia.

PMID- 9263422
TI  - Sonographic prediction of malignancy in adnexal masses using multivariate
      logistic regression analysis.
AB  - The aim of the study was to assign a probability of malignancy for any patient
      with an adnexal tumor by the application of multivariate logistic regression
      analysis to variables recorded at the time of pelvic sonography. Sixty-seven
      women with known adnexal masses were examined using transvaginal B-mode and color
      Doppler imaging. For each patient the variables included: (1) age, (2) maximum
      tumor diameter, (3) tumor volume, (4) unilocularity (presence (0) or absence(1)),
      (5) papillary projections (presence (1) or absence (0)), (6) random echogenicity
      (presence (1) or absence (0)), (7) highest peak systolic velocity (PSV), (8) time
      averaged maximum velocity (TAMXV), (9) pulsatility index (PI) and (10) resistance
      index (RI). The TAMXV, PI and RI were those associated with the highest PSV.
      These ten independent variables and the final histological diagnosis for each
      patient (the dependent variable) were used for the regression analysis.
      Approximately 75% of the entire dataset was randomly selected for generating the
      regression model. The remaining 25% was used as the testing set for cross
      validation of the model. In the entire dataset there were 52 women with benign,
      three with borderline and 12 with invasive ovarian tumors. Regression analysis on
      the ten variables resulted in the retention of only 'age', 'papillary projection
      score' and 'TAMXV' as significantly contributing to predicting the presence or
      absence of malignancy. The probability of malignancy for any patient was given by
      solving the equation: Probability = 1/(1 + e-z) where e is the base value for
      natural logarithms and z = (0.1273 x Age) + (0.2794 x TAMXV) + (4.4136 x
      Papillary projections score) - 14.2046. Cross-validation of the model on the test
      set of data gave a 100% sensitivity and specificity. However, for the entire
      dataset the best sensitivity and specificity were 93.3 and 90.4%, respectively,
      at a cut-off value of 25% probability of malignancy. In conclusion, multivariate
      logistic regression analysis enables the calculation of probability of malignancy
      for any patient with a known adnexal mass. The accuracy of this prediction
      appears to be better than that of morphological or Doppler criteria when the
      latter are used independently. The value of this model needs to be tested
      prospectively.

PMID- 9263423
TI  - Optimized differential diagnosis of breast lesions by combined B-mode and color
      Doppler sonography.
AB  - To optimize the sensitivity and specificity of gray-scale imaging and color
      Doppler in breast tumor diagnosis, alone and in combination, 89 women with
      palpable breast masses were scanned preoperatively and standard parameters were
      determined in both modes. Parameters significant for differentiation of benign
      and malignant tumors identified using univariate analysis were combined and
      weighted using multivariate analysis (multiple logistic regression).
      Histologically 59 tumors were malignant and 30 benign. Gray-scale sonography
      alone achieved a sensitivity of 88% and a specificity of 96% using the parameters
      of wall structure and posterior acoustic attenuation. Color Doppler achieved a
      sensitivity of 85% and a specificity of 79% using resistance index and
      pulsatility index as parameters. Combination of both methods yielded an accurate
      diagnosis in 84/87 patients (sonographic lesion correlates were absent in two
      cases), equivalent to a sensitivity of 97% and a specificity of 96%. Thus the
      individual diagnostic performance of gray-scale imaging and color Doppler
      sonography in palpable breast disease is further enhanced using multiple logistic
      regression to combine independently significant parameters.

PMID- 9263424
TI  - Expression of thymidine phosphorylase in uterine sarcoma and uterine leiomyoma:
      association with microvessel density and Doppler blood flow analysis.
AB  - The aim of this study was to determine whether the expression of thymidine
      phosphorylase (TP) by uterine sarcoma and leiomyoma cells is associated with the
      density of microvessels within the tumor, and with Doppler ultrasound-derived
      peak systolic velocity (PSV) of blood flow. Sections of tissue from four uterine
      sarcomas and 41 uterine leiomyomas which had been used in a previous study to
      determine intratumoral peak systolic velocity were analyzed for the cellular
      expression of TP and the intratumoral density of microvessels by
      immunohistochemistry, using monoclonal antibody to TP and factor VIII-related
      antigen, respectively. The main outcome measures were whether or not the tumor
      cells were TP-positive or TP-negative, and the microvessel count within each
      tumor type. Uterine sarcomata were classified as TP-positive and uterine
      leiomyomata as TP-negative. The microvessel count in uterine sarcomas was
      significantly higher than that in uterine leiomyomas (p = 0.002, Mann-Whitney U
      test). We concluded that the expression of TP by uterine sarcoma cells is
      associated with an increase in microvessel density and with a higher peak
      systolic velocity.

PMID- 9263426
TI  - Hepatic mesenchymal hamartoma: a pediatric tumor that may be diagnosed
      prenatally.
AB  - Hepatic mesenchymal hamartoma is a benign tumor, defined as an excessive focal
      overgrowth of mature normal cells and stroma native to the liver. The increasing
      popularity of antenatal scanning has resulted in in utero diagnosis of congenital
      malformations and anomalies that previously became apparent only after delivery.
      Herein, we present a rare case of fetal mesenchymal hamartoma of the liver, which
      was initially sonographically detected at 29 weeks of gestation. A brief
      literature survey and obstetric recommendations for management and monitoring of
      such rare cases are included.

PMID- 9263425
TI  - Uterine cavity assessment prior to in vitro fertilization: comparison of
      transvaginal scanning, saline contrast hysterosonography and hysteroscopy.
AB  - A total of 44 patients undergoing in vitro fertilization (IVF) and requiring
      uterine cavity assessment agreed to have both saline contrast hysterosonography
      (SCHS) and hysteroscopy. SCHS was performed following a baseline transvaginal
      scan by injection of saline into the uterine cavity during continuous scanning.
      Hysteroscopy was performed with a flexible fiberscope with a 3.6-mm outer
      diameter; 38 of 44 women (86%) underwent both procedures. Hysteroscopy diagnosed
      intrauterine abnormalities in 16 women. SCHS was in complete agreement in 13 of
      16 cases. As a screening test for any cavity abnormality, SCHS had a 87.5%
      sensitivity, 100% specificity, 100% positive predictive value and 91.6% negative
      predictive value. In 14 women, an abnormal uterine cavity was apparent on
      transvaginal scanning (TVS). However, TVS, unlike SCHS, could not (1) confidently
      diagnose submucosal fibroids in the presence of a uterus with multiple fibroids;
      (2) distinguish between a hyperplastic endometrium and a large polyp; or (3)
      differentiate between an arcuate and a septate uterus. In addition, ovarian
      pathology was diagnosed on TVS in five women: endometrioma (n = 1), complex cysts
      (n = 2) and polycystic ovaries (n = 2). SCHS is a simple, accurate, well
      tolerated procedure that can be performed within a fertility unit, avoiding
      invasive and expensive diagnostic hysteroscopy. Significant findings can be
      treated by operative hysteroscopy prior to commencing an IVF treatment cycle.

PMID- 9263427
TI  - Sonodynamic changes after transcatheter arterial embolization in a vaginal
      hemangioma: case report.
AB  - A 36-year-old pregnant woman with a rapidly growing hemangioma in the vagina was
      treated by transcatheter arterial embolization after delivery. Blood flow
      characteristics within the tumor were evaluated using transvaginal color Doppler
      ultrasound both before and after the embolization. The vascular resistance in the
      tumor vessels within the vaginal hemangioma was observed to be significantly
      decreased; the tumor reduced in volume following this non-surgical treatment.

PMID- 9263428
TI  - Clinical and perinatal sonographic features of congenital adrenal cystic
      neuroblastoma: a case report with review of the literature.
AB  - Cystic formation in association with adrenal neuroblastoma may be related to
      hemorrhage and necrosis of the tumor. We present an unusual case of congenital
      cystic fetal neuroblastoma of the right adrenal gland detected at 37 weeks'
      gestation which evolved into a complex echogenic mass 6 weeks after birth.
      Surgical exploration revealed a 3.5 x 3 x 3 cm right complex adrenal tumor which
      was resected. The infant did well 10 weeks after tumor resection. Typically
      adrenal hemorrhage may appear sonographically to be entirely echogenic, of mixed
      echogenicity, or anechoic when first imaged. Gradually, the texture of the
      hematoma will evolve and become more cystic and echolucent on follow-up
      ultrasound examinations. In contrast, our case of congenital adrenal cystic
      neuroblastoma became more complex after resolution of the hemorrhagic cyst. This
      case suggests that adrenal hemorrhagic and adrenal cystic neuroblastoma with a
      hemorrhagic cyst have different sonographic appearances. We suggest that
      additional imaging and surgical intervention should be considered whenever a
      cystic suprarenal mass becomes more complex after resolution and demonstrates no
      significant decrease in size in postnatal examinations.

PMID- 9263429
TI  - Incrustation of contraceptive devices: ultrasound as a diagnostic tool.

PMID- 9263430
TI  - Modeling inhibition of type II units in the dorsal cochlear nucleus.
AB  - Type II units in the dorsal cochlear nucleus (DCN) are characterized by vigorous
      but nonmonotonic responses to best frequency tones as a function of sound
      pressure level, and relatively weak responses to noise. A model of DCN neural
      circuitry was used to explore two hypothetical mechanisms by which neurons may be
      endowed with type II unit response properties. Both mechanisms assume that type
      II units receive excitatory input from auditory nerve (AN) fibers and inhibitory
      input from an unspecified class of cochlear nucleus interneurons that also
      receive excitatory AN input. The first mechanism, a lateral inhibition (LI)
      model, supposes that type II units receive inhibitory input from a number of
      narrowly tuned interneurons whose best frequencies (BFs) flank the BF of the type
      II unit. Tonal stimuli near BF result in only weak inhibitory input, but
      broadband stimuli recruit enough lateral inhibitors to greatly weaken the type II
      unit response. The second mechanism, a wideband inhibition (WBI) model, supposes
      that type II units receive inhibitory input from interneurons that are broadly
      tuned so that they respond more vigorously to broadband stimuli than to tones.
      Physiological and anatomical evidence points to the possible existence of such a
      class of neurons in the cochlear nucleus. The model extends an earlier computer
      model of an iso-frequency DCN patch to multiple frequency slices and adds a
      population of interneurons to provide the inhibition to model type II units
      (called 12-cells). The results show that both mechanisms accurately simulate
      responses of type II units to tones and noise. An experimental paradigm for
      distinguishing the two mechanisms is proposed.

PMID- 9263431
TI  - Classification of protein families and detection of the determinant residues with
      an improved self-organizing map.
AB  - Using a SOM (self-organizing map) we can classify sequences within a protein
      family into subgroups that generally correspond to biological subcategories.
      These maps tend to show sequence similarity as proximity in the map. Combining
      maps generated at different levels of resolution, the structure of relations in
      protein families can be captured that could not otherwise be represented in a
      single map. The underlying representation of maps enables us to retrieve
      characteristic sequence patterns for individual subgroups of sequences. Such
      patterns tend to correspond to functionally important regions. We present a
      modified SOM algorithm that includes a convergence test that dynamically controls
      the learning parameters to adapt them to the learning set instead of being fixed
      and externally optimized by trial and error. Given the variability of protein
      family size and distribution, the addition of this features is necessary. The
      method is successfully tested with a number of families. The rab family of small
      GTPases is used to illustrate the performance of the method.

PMID- 9263432
TI  - A dynamic model of motor basal ganglia functions.
AB  - Fast aiming movements were measured in a choice reaction paradigm in a healthy
      control group and in Parkinsonian patients. The patients were tested without
      ('off') and with 3,4-dihydroxyphenylalanine ('on') (L-dopa) medication. The
      movement trajectories were used to estimate the parameters of a dynamic linear
      model. The model is based on the functional structure of the basal ganglia
      thalamocortical circuit with direct and indirect pathways linking the putamen to
      the basal ganglia output nuclei (Albin et al. 1989). The output of the circuit is
      connected to a model for the motor neuron-musculo-skeletal system. The gain kd
      for the direct pathway and the gain ki for the indirect pathway were estimated.
      They were found to be significantly decreased for Parkinsonian patients in 'off'
      compared with the control group. L-dopa therapy in Parkinsonian patients
      increased the gains of the direct and the indirect pathway almost to normal
      values which implies that the long-term dopamine level in the striatum was
      excitatory for the direct and for the indirect pathway. This result is restricted
      to movements of correct size. For movements of diminished size, which are typical
      for Parkinsonian patients, the model predicts that the dopamine level in the
      striatum is excitatory for the direct pathway but inhibitory for the indirect
      pathway. The simulated values for neuronal activities are in agreement with
      expected values according to the experimental data. The proposed model of the
      'motor' basal ganglia thalamocortical circuit implies that information about
      biomechanical properties of the musculo-skeletal system is stored in the 'motor'
      basal ganglia-thalamocortical circuit, and that the basal ganglia are involved in
      computation of the desired movement amplitude.

PMID- 9263433
TI  - Is the alpha rhythm a control parameter for brain responses?
AB  - The main goal of the present study is to develop a conceptual analysis of alpha
      response in the brain based on single sweep evaluation. A new method was employed
      to estimate a set of single-sweep parameters and quantify the oscillatory
      behaviour of single, electroencephalograph (EEG) sweeps. It was aimed to
      demonstrate that brain alpha responses are governed by spontaneous alpha activity
      and to validate the principle of brain response excitability. Because the
      spontaneous alpha activity depends on both the topology of recording and the
      subject's age, topology and age models were used. Spontaneous and evoked alpha
      activity were recorded at frontal and occipital sites in three groups of
      subjects: 3-year-old children, young adults and middle-aged subjects. Amplitude,
      enhancement and phase-locking of single alpha responses to visual stimuli were
      analysed. Major results showed that; (1) visual alpha responses could be recorded
      only if the alpha rhythm was developed in the spontaneous EEG independent of
      electrode location; (2) middle-aged adults showed more expressed frontal
      spontaneous alpha activity in comparison with young adults; (3) accordingly,
      alpha responses with higher amplitude and stronger phase-locking were produced
      over the frontal brain area in middle-aged than young adults. These results
      validate the principle of brain response excitability and demonstrate that a
      shift towards frontal brain areas for both the spontaneous and evoked alpha
      activity occurs with increasing age in adults. The results are discussed in the
      context of the diffuse and distributed alpha system of the brain. Age-dependent
      changes in frontal alpha activity are suggested to be related to frontal brain
      functioning during aging.

PMID- 9263434
TI  - The influence of prostaglandin E1 on in vitro transcription of sperm chromatin
      from healthy males.
AB  - Run-on transcription experiments with sonicated chromatin from healthy
      individuals in the presence and absence of prostaglandin E1 showed different
      levels of transcription. Thus the level of incorporation of 14C-UTP into pre-mRNA
      proved to be about twice as high in the presence of postaglandin E1 as in the
      controls. The kinetic data of the in vitro transcription indicated that there
      were two peaks of incorporation of 14C-UTP into RNA both in the controls and in
      prostaglandin E1 treated probes but at different time intervals. The results show
      that prostaglandin E1 has a stimulatory effect on in vitro transcription of
      chromatin, isolated from normal patients.

PMID- 9263436
TI  - Far-field fluorescence microscopy with three-dimensional resolution in the 100-nm
      range.
AB  - We report three-dimensional (3D) microscopy with nearly isotropic resolution in
      the lambda/5-lambda/10 range. Our approach combines 4PI-confocal two-photon
      fluorescence microscopy with image restoration. The 3D resolution is demonstrated
      with densely clustered beads as well as with F-actin fibers in mouse fibroblast
      cells. A comparison with unrestored two-photon confocal images reveals a total
      reduction of the uncertainty volume up to a factor of 15.

PMID- 9263435
TI  - The dynamics of inflammation of the anterior eye in a novel experimental model
      for hypersensitivity.
AB  - A novel immunologically provoked inflammatory process was studied in guinea pigs.
      The animals were immunized by i.p. injections of ovalbumin (OA) suspended in
      Freund's complete adjuvant and challenged by the application of OA into the
      conjunctival sac of one eye. An inflammatory reaction was seen a few minutes
      after provocation and lasted normally for 4-7 days. The process was characterized
      by early damage to the epithelial layer which was partly detached in small
      flakes; an intense tearing with the tear fluid soon turning mucous and then
      purulent; vasodilation in the bulbar conjunctiva, in particular towards the
      limbal region; margination and emigration of polymorphonuclear, and to a lesser
      extent, eosinophil, leucocytes which migrated towards and infiltrated the surface
      epithelial layer. Subsequently, the dominant cell type infiltrating the submucosa
      was lymphocytes. Later, opacity of the cornea occurred, probably due to oedema
      and neovascularization of the stroma progressing centrally from the periphery.
      When the antigenic challenge was repeated, thickening of the conjunctival mucosa,
      and neoformation of collagen bundles in the submucosa led to the swelling of the
      upper lids. The facets of this inflammatory trauma may not fit easily into any of
      the classical types of hypersensitivity. Rather, it may combine features of
      several of them, at least type 1 and type 4. This syndrome shows several features
      similar to those of human vernal keratoconjunctivitis.

PMID- 9263437
TI  - Three-dimensional reconstruction of colon carcinoma metastases in liver.
AB  - Resection of liver metastases in patients with colon cancer increases survival
      but success depends on removal of all tumour tissue. For this purpose,
      understanding of spatial relationships between metastases and liver architecture
      is essential. Because metastatic cancer growth is essentially a three-dimensional
      (3D) event, we decided to apply 3D reconstruction techniques to study these
      spatial relationships between metastases and liver structures such as blood
      vessels, stroma and the liver capsule (Glisson's capsule). Colon carcinoma
      metastases were experimentally induced in rat liver by injection of colon cancer
      cells (CC531) into the portal vein. Three weeks later, livers from these animals
      and control livers were removed and immediately frozen in liquid nitrogen. Thirty
      seven to 110 consecutive sections were used for each 3D reconstruction of 26
      metastases in eight livers. Contours of different structures were stained by
      (immuno)histochemical means, traced in each section and stored in a database.
      From the contour model, a volume model was generated. Among the 26 metastases,
      seven were found to grow distantly from the liver capsule. They were small and
      consisted of well-differentiated cancer cells that were totally surrounded by a
      basement membrane and stroma which was always connected with adjacent blood
      vessels of a portal tract. The remaining 19 metastases showed a more advanced
      pattern of development. Infiltration of poorly differentiated colon cancer cells
      progressed through the stroma at various sites and areas of direct contact
      between cancer cells and hepatocytes were frequently found. This type of
      outgrowth of cancer cells was only found when metastases had made contact with
      the liver capsule. However, some areas in sections of these advanced stages still
      resembled small metastases. On the basis of these findings, we conclude that
      stroma-affects the differentiation pattern of cancer cells and has at least a
      dual role in tumour growth. On the one hand it limits invasion of cancer cells in
      the surrounding host tissue. On the other hand, stroma formation at the capsule,
      which consists mainly of granulation tissue, facilitates outgrowth of the
      tumours. Furthermore, our 3D reconstructions demonstrate the spatial
      heterogeneity of larger metastases and the importance of a 3D approach to
      understand growth and development of metastases in general and colon cancer
      metastases in the liver in particular.

PMID- 9263438
TI  - Analysis of cardiac function by MRI and stereology.
AB  - Design-based stereology and phase contrast magnetic resonance imaging (MRI) were
      combined to monitor changes in the volume of the four chambers of the human heart
      during the cardiac cycle. The data set consisted of 18 adjacent slices (or
      'scanning levels') of 0.5 cm thickness, perpendicular to the long axis of the
      body, and encompassing the whole heart of a healthy volunteer. At each scanning
      level, a cardiac gated MR image was obtained at each of 16 equally spaced time
      frames within the cardiac cycle. Given stationarity with respect to time, absence
      of image artefacts and appropriate definition of chamber boundaries, for each
      time frame unbiased estimates of total blood volume in the relevant heart
      chambers were efficiently obtained using the Cavalieri method and point counting.
      Combined with a proper MRI acquisition, modern stereological methods constitute
      an efficient and reliable tool to quantify cardiac function noninvasively.

PMID- 9263439
TI  - Scanning (atomic) force microscopy imaging of earthworm haemoglobin calibrated
      with spherical colloidal gold particles.
AB  - Scanning (atomic) force microscopy (SFM) permits high-resolution imaging of a
      biological specimen in physiological solutions. Untreated extracellular
      haemoglobin molecules of the common North American earthworm. Lumbricus
      terrestris, were imaged in NH4Ac solution using calibrated SFM. Individual
      molecules and their top and side views were clearly identified and were
      comparable with the images of the same molecule obtained by scanning transmission
      electron microscopy (STEM). A central depression, the presumed mouth of the hole,
      was detected. We analysed 75 individual molecules for their lateral dimensions.
      Compression varied for different molecules, presumably because of the variation
      of the interaction between the SFM tip and the protein molecule. Two effective
      heights which correspond to the heights of the points of the haemoglobin
      molecules first and last touched by the tip, h1 and h2, respectively, were
      measured for each protein and ranged between 1.58 and 16.2 nm for h1 and 1.23 and
      13.6 nm for h2. The apparent diameter was measured and ranged from 44.9 to 86.6
      nm (63.2 +/- 10.5 nm, n = 75), which is about twice the diameter of the molecule
      reported by STEM for the top view orientation. The higher the measured effective
      heights, the worse was the tip convolution effect. In order to determine the tip
      parameters (semivertical angle, curvature of radius and the cut-off height) and
      to calibrate images of earthworm haemoglobin molecules, spherical gold particles
      were scanned as standards. The tip sectional radii at distances of h1 and h2
      above the tip apex were subtracted from the apparent diameter of the protein. The
      calibrated lateral dimension was 29.1 +/- 3.85 nm, which is close to the reported
      scanning transmission electron microscopy data 30.0 +/- 0.8 nm. The results
      presented here demonstrate that the calibration approach of imaging gold
      particles is practical and relatively accurate. Calibrated SFM imaging can be
      applied to the study of other biomacromolecules.

PMID- 9263440
TI  - Immunohistochemical processing of tissue which allows for embedding in Araldite,
      and orientation and correlation between light and electron microscopic staining.
AB  - This paper describes a simple and efficient method for the immunohistochemical
      processing of tissue sections on glass slides and the subsequent transfer of the
      entire section to an Araldite medium. These sections present in one plane can
      then be orientated and when cut provide the user with whole tissue, free from
      gaps due to folding. This procedure therefore enables the changes in protein
      concentration and distribution to be assessed and correlated within and between
      different cells at the light and electron microscopic level. This procedure may
      be of use in other microscopic techniques studies.

PMID- 9263441
TI  - Minimal inhibitory concentrations of sulbactam/ampicillin against drug sensitive
      and drug resistant isolates of Mycobacterium tuberculosis.
AB  - A total of 92 isolates of Mycobacterium tuberculosis consisting of equal numbers
      of sensitive and resistant strains was tested for their susceptibility to
      sulbactam and ampicillin (in the ratio of 1:2) on Lowenstein-Jensen (LJ) and 7H11
      agar media. The geometric mean MIC was 63.97 micrograms/ml for the drug sensitive
      strains and 65.92 micrograms/ml for the resistant strains, and the overall mean
      was 65.01 micrograms/ml. The high MIC on LJ medium could be attributed to the
      higher protein content which resulted in greater binding of sulbactam/ampicillin.
      On the other hand, the geometric mean MIC on 7H11 medium was 26.73 micrograms/ml
      for sensitive strains and 23.82 micrograms/ml for resistant strains; the overall
      mean being 25.23 micrograms/ml. Although these MICs of sulbactam-ampicillin are
      higher than those reported earlier, they can be easily achieved in serum. Further
      studies on experimental tuberculosis and in humans will be needed to prove the
      efficacy of sulbactam/ampicillin in the treatment of patients with multidrug
      resistant tuberculosis.

PMID- 9263442
TI  - Interaction of synthetic pyrethroids with micro-organisms: a review.
AB  - Pyrethroids are widely used insecticides in agriculture and public health. They
      are photostable with high insecticidal activity and low toxicity to birds and
      mammals. At lower concentrations, they are less toxic, but have significant
      effects on micro-organisms at high concentrations. Pyrethroids constitute about
      25% of the total pesticides used in the world and due to the restricted use of
      organochlorine insecticides, the application of pyrethroids is expected to
      increase. The present review deals with the interaction of pyrethroids with micro
      organisms.

PMID- 9263443
TI  - Antibiotic activity of strains of the genus Arthrinium on bacteria and yeasts.

PMID- 9263444
TI  - Immunochemical localization of CAMP factor (protein B) in Streptococcus
      agalactiae.
AB  - Biochemical and immunochemical investigations were used in order to study the
      quantitative and qualitative localization of CAMP factor (protein B) in the cell
      fractions of Streptococcus agalactiae during the logarithmic growth phase. The
      dynamic quantitative distribution of CAMP factor activity showed that higher
      concentrations of CAMP factor were found in the cytoplasm than in the cell
      envelopes. A maximal intracellular accumulation of CAMP factor activity was
      observed in the late log phase. Immunoblotting analysis using specific anti-CAMP
      IgG showed that CAMP factor could be detected in the different cell fractions of
      S. agalactiae. During the early log phase, CAMP factor was present as a single 25
      kD protein band in the cytoplasm; white it was found together with its 26 and 24
      kD satellite proteins in the cytoplasmic membrane and the cell wall as well as in
      all the cell fractions in the mid- and late log phases. Intracellular CAMP factor
      exhibited the same antigenic and amphiphilic behaviour as the extracellular
      species. Additionally, a newly discovered amphiphilic protein of approximately 54
      kD which exhibited similar antigenicity with the CAMP factor was present in all
      the cell fractions. Immunoelectron microscopic examinations using ferritin
      labelled antibodies revealed that CAMP factor was mainly found in the cytoplasm,
      whereas it was associated to a minor extent with the cell envelopes.
      Interestingly, an accumulation of CAMP factor was also localized either at the
      sites of cross-wall initiation or at the cell surfaces where the cell wall became
      autolysed.

PMID- 9263445
TI  - Alteration of the symbiotic properties of Rhizobium meliloti by plasmid
      manipulations.
AB  - Mutants with symbiotic activity were obtained by random Tn5-Mob mutagenesis of
      Rhizobium meliloti 41. The place of the Tn5 insertion was localized on a cryptic
      middle-sized plasmid pRme41a. Mobilization of the labelled plasmid pRme41a::Tn5
      Mob into R. meliloti 114, which did not contain such a plasmid led to a complete
      loss of the nodulation ability of the recipient strain. The Nod-phenotype was a
      result of a large deletion in the symbiotic (pSym) plasmid of R. meliloti 114.

PMID- 9263446
TI  - Alteration of Escherichia coli O157:H7 growth and molecular fingerprint by the
      neuroendocrine hormone noradrenaline.
AB  - The neuroendocrine hormone noradrenaline has previously been shown to increase
      the growth of Gram-negative bacteria. To determine whether these results were due
      to noradrenaline-induced genetic rearrangements, arbitrarily-primed PCR utilizing
      a large number of primers of varying G + C content was performed on Escherichia
      coli O157:H7 grown in serum-based media at low initial inocula in order to
      approximate in vivo conditions. In addition to increased growth, bacteria grown
      in noradrenaline supplemented media displayed a different molecular fingerprint
      compared with growth in non-noradrenaline supplemented media with a minority of
      the primers tested. Differences in fingerprint patterns between noradrenaline
      supplemented and non-supplemented growth bacteria were greatest in the late
      logarithmic to early stationary phase of growth compared with the late stationary
      phase. These results suggest that the neuroendocrine hormonal environment of the
      host may provide environmental signals which lead to genetic rearrangements in
      the infectious agent and possibly alterations in subsequent pathogenicity.

PMID- 9263447
TI  - Recognition of bacterial avirulence proteins occurs inside the plant cell: a
      general phenomenon in resistance to bacterial diseases?
AB  - One of the recent exciting developments in the research area of plant-microbe
      interactions is a breakthrough in understanding part of the initial signalling
      between avirulent Gram-negative bacteria and resistant plants. For resistance to
      occur, both interacting organisms need to express matching genes, the plant
      resistance gene and the bacterial avirulence gene. The biochemical function of
      bacterial avirulence genes and the nature of the signal molecules recognized by
      the plant have been a mystery for a long time. Recently, several laboratories
      have shown that bacterial avirulence proteins function as elicitors that are
      perceived within the plant cell.

PMID- 9263448
TI  - Developmental regulation of the gibberellin biosynthetic gene GA1 in Arabidopsis
      thaliana.
AB  - The GA1 gene of Arabidopsis thaliana encodes ent-kaurene synthase A (KSA), which
      catalyzes the first committed step in the biosynthetic pathway of the plant
      hormone gibberellin (GA). Its location in the GA biosynthetic pathway has led to
      speculation that KSA regulation is one of the controlling steps. However, because
      KSA activity is so low that it is only measurable in Arabidopsis siliques, GA1
      promoter-GUS reporter gene fusions and quantitative reverse transcriptase
      polymerase chain reaction (RT-PCR) were used to examine the expression pattern of
      GA1. The results from this study indicate that GA1 gene expression is highly
      regulated during growth and development, and it is restricted to specific cell
      types at the sites of expression. GA1 promoter activity is highest in rapidly
      growing tissues, e.g. shoot apicas, root tips, developing flowers and seeds. It
      is also active in the vascular tissue of some non-growing organs, such as
      expanded leaves, suggesting that these leaves may be a site of GA synthesis for
      transport to other organs. It was also found that the first one or two introns in
      the GA1 gene are required for proper expression. Because of the high degree of
      regulation, GA1 may act as a gatekeeper, controlling the flow of metabolites into
      the GA biosynthetic pathway, while the levels of specific bioactive GAs are
      controlled by other downstream steps.

PMID- 9263449
TI  - Use of Arabidopsis recombinant inbred lines reveals a monogenic and a novel
      digenic resistance mechanism to Xanthomonas campestris pv campestris.
AB  - Infiltration of the Arabidopsis thaliana accession Landsberg erecta (Ler) with
      Xanthomonas campestris pv campestris isolate 2D520 results in extensive necrosis
      and limited chlorosis within 5-6 days post-inoculation (d.p.i.), which can lead
      to systemic necrosis within 23 d.p.i. in contrast, the accession Columbia (Col)
      remains asymptomatic after infiltration. Although both accessions support
      bacterial growth, 5-28-fold more bacteria are present in Ler than in Col leaf
      tissue. Inheritance studies indicate that three independent, dominant or
      partially dominant, nuclear genes condition resistance to X. c. campestris 2D520.
      The major gene, termed RXC2, conditions monogenic resistance to X. c.; campestris
      and was mapped to a 5.5 cM interval of chromosome V. Segregation data indicate
      that the locus RXC3 in conjunction with RXC4 confers digenic resistance to X. c.
      campestris. The combined action of RXC3 and RXC4 is correlated with a suppression
      of in planta bacterial levels and a suppression of symptoms relative to Ler. The
      RXC3 + RXC4-mediated resistance is novel in that although the Col allele of RXC4
      contributes positively to resistance, it is the Ler and not the Col allele of
      RXC3 that contributes positively to resistance. RXC3 was mapped to the bottom arm
      of chromosome V in a 2.7 cM interval within the major recognition gene complex
      MRC-J, a cluster of genes involved in disease resistance. RXC4 was mapped to a 12
      cM interval on chromosome II that also contains RXC1, a gene conferring tolerance
      to X. c. campestris.

PMID- 9263450
TI  - Physical mapping of the 5S ribosomal RNA genes in Arabidopsis thaliana by multi
      color fluorescence in situ hybridization with cosmid clones.
AB  - The 5S ribosomal RNA genes were mapped to mitotic chromosomes of Arabidopsis
      thaliana by fluorescence in situ hybridization (FISH). In the ecotype Landsberg
      erecta, hybridization signals appeared on three pairs of chromosomes, two of
      which were metacentric and the other acrocentric. Hybridization signals on one
      pair of metacentric chromosomes were much stronger than those on the acrocentric
      and the other pair of metacentric chromosomes, probably reflecting the number of
      copies of the genes on the chromosomes. Other ecotypes, Columbia and
      Wassilewskija, had similar chromosomal distribution of the genes, but the
      hybridization signals on one pair of metacentric chromosomes were very weak, and
      detectable only in chromosomes prepared from young flower buds. The chromosomes
      and arms carrying the 5S rDNA were identified by multi-color FISH with cosmid
      clones and a centromeric 180 bp repeat as co-probes. The metacentric chromosome 5
      and its L arm carries the largest cluster of the genes, and the short arm of
      acrocentric chromosome 4 carries a small cluster in all three ecotypes.
      Chromosome 3 had another small cluster of 5S rRNA genes on its L arm. Chromosome
      1 and 2 had no 5S rDNA cluster, but they are morphologically distinguishable;
      chromosome 1 is metacentric and 2 acrocentric. Using the 5S rDNA as a probe,
      therefore, all chromosomes of A. thaliana could be identified by FISH. Chromosome
      1 is large and metacentric; chromosome 2 is acrocentric carrying 18S-5.8S-25S
      rDNA clusters on its short arm; chromosome 3 is metacentric carrying a small
      cluster of 5S rDNA genes on its L arm; chromosome 4 is acrocentric carrying both
      18S-5.8S-25S and 5S rDNAs on its short (L) arm; and/chromosome 5 is metacentric
      carrying a large cluster of 5S rDNA on its L arm.

PMID- 9263451
TI  - Possible involvement of differential splicing in regulation of the activity of
      Arabidopsis ANP1 that is related to mitogen-activated protein kinase kinase
      kinases (MAPKKKs).
AB  - Three types of Arabidopsis cDNA (cANP1, cANP2 and cANP3) have been isolated that
      encode putative protein kinases, designated ANP1, ANP2 and ANP3. These kinases
      exhibit a high degree of homology to NPK1, a tobacco protein that is a member of
      the family of mitogen-activated protein kinase kinase kinases (MAPKKKs), which
      appears to function in the proliferation of tobacco cells. The predicted amino
      acid sequences of the kinase domains in the amino-terminal halves of the ANPs
      were more than 80% identical to that of NPK1, while the kinase-unrelated regions
      in the carboxy-terminal halves exhibited relatively low homology. Two species of
      cANP1 were identified, ANP1L cDNA (cANP1L) and ANP1S cDNA (cANP1S), which were
      derived from a single ANP1 gene: the former had an intron-like sequence in the
      coding region for the kinase-unrelated region, while the latter did not include
      such an intron-like sequence. cANP1L encoded a putative protein with both kinase
      and kinase-unrelated domains, resembling NPK1, whereas cANP1S encoded only the
      amino-terminal kinase domain because the intron-like sequence was absent, with
      resulting elimination of most of the kinase-unrelated region. Genetic analysis
      with mutant yeast cells showed that over-expression of cANP1L or of cANP1S
      activated the mating pheromone-responsive signal pathway which is mediated by a
      MAP kinase cascade. Moreover, the extent of such activation by cANP1S was greater
      than that by cANP1L. These results predict that differential splicing of the
      intron-like sequence in the ANP1 transcript might be at least one of the
      molecular mechanisms involved in the generation of active ANP1 protein kinase.

PMID- 9263453
TI  - Interaction of the maize and Arabidopsis kinase interaction domains with a subset
      of receptor-like protein kinases: implications for transmembrane signaling in
      plants.
AB  - The kinase interaction (KI) domain of kinase-associated protein phosphatase
      (KAPP) interacts with the phosphorylated form of an Arabidopsis thaliana receptor
      like protein kinase (RLK). The KI domain may recruit KAPP into an RLK-initiated
      signaling complex. To examine additional roles that this domain may play in plant
      signal transduction, a search was conducted for other KI domain-containing
      proteins. One gene was isolated which encodes a KI domain, the maize homolog of
      KAPP. To test whether the maize KI domain associates with other maize proteins,
      it was used as a probe in a protein-protein interaction cloning strategy. A new
      maize RLK, KI domain interacting kinase 1 (KIK1), was identified by its
      interaction with the maize KI domain. The maize KI domain and the KIK1 kinase
      domain association required phosphorylation of the kinase. This work establishes
      that the KI domain phosphorylation-dependent signaling mechanism is present in
      both monocots and dicots. Additionally, it was determined that both the maize and
      Arabidopsis KI domains interact with several but not all of the active RLKs
      assayed. These multiple associations imply that KAPP may function in a number of
      RLK-initiated signaling pathways.

PMID- 9263452
TI  - Molecular characterization of a phloem-specific gene encoding the filament
      protein, phloem protein 1 (PP1), from Cucurbita maxima.
AB  - Sieve elements in the phloem of most angiosperms contain proteinaceous filaments
      and aggregates called P-protein. In the genus Cucurbita, these filaments are
      composed of two major proteins: PP1, the phloem filament protein, and PP2, the
      phloem lactin. The gene encoding the phloem filament protein in pumpkin
      (Cucurbita maxima Duch.) has been isolated and characterized. Nucleotide sequence
      analysis of the reconstructed gene gPP1 revealed a continuous 2430 bp protein
      coding sequence, with no introns, encoding an 809 amino acid polypeptide. The
      deduced polypeptide had characteristics of PP1 and contained a 15 amino acid
      sequence determined by N-terminal peptide sequence analysis of PP1. The sequence
      of PP1 was highly repetitive with four 200 amino acid sequence domains containing
      structural motifs in common with cysteine proteinase inhibitors. Expression of
      the PP1 gene was detected in roots, hypocotyls, cotyledons, stems, and leaves of
      pumpkin plants. PP1 and its mRNA accumulated in pumpkin hypocotyls during the
      period of rapid hypocotyl elongation after which mRNA levels declined, while
      protein levels remained elevated. PP1 was immunolocalized in slime plugs and P
      protein bodies in sieve elements of the phloem. Occasionally, PP1 was detected in
      companion cells. PP1 mRNA was localized by in situ hybridization in companion
      cells at early stages of vascular differentiation. The developmental accumulation
      and localization of PP1 and its mRNA paralleled the phloem lactin, further
      suggesting an interaction between these phloem-specific proteins.

PMID- 9263454
TI  - Structural cell-wall proteins in protoxylem development: evidence for a repair
      process mediated by a glycine-rich protein.
AB  - Polyclonal antibodies were used to localize structural cell-wall proteins in
      differentiating protoxylem elements in etiolated bean and soybean hypocotyls at
      the light- and electron-microscopic level. A proline-rich protein was localized
      in the lignified secondary walls, but not in the primary walls of protoxylem
      elements, which remain unlignified, as shown with lignin-specific antibodies.
      Secretion of the proline-rich protein was observed during lignification in
      different cell types. A glycine-rich protein (GRP1.8) was specifically localized
      in the modified primary walls of mature protoxylem elements and in cell corners
      between xylem elements and xylem parenchyma cells. The protein was secreted by
      Golgi bodies both in protoxylem cells after the lignification of their secondary
      walls and in the surrounding xylem parenchyma cells. The modified primary walls
      of protoxylem elements were visualized under the light microscope as filaments or
      sheets staining distinctly with the protein stain Coomassie blue. Electron
      micrographs of these walls show that they are composed of an amorphous material
      of moderate electron-density and of polysaccharide microfibrils. These materials
      form a three-dimensional network, interconnecting the ring- or spiral-shaped
      secondary wall thickenings of protoxylem elements and xylem parenchyma cells. The
      results demonstrate that the modified primary walls of protoxylem cells are not
      simply breakdown products due to partial hydrolysis and passive elongation, as
      believed until now. Extensive repair processes produces cell walls with unique
      staining properties. It is concluded that these walls are unusually rich in
      protein and therefore have special chemical and physical properties.

PMID- 9263455
TI  - Very-long-chain fatty acid biosynthesis is controlled through the expression and
      specificity of the condensing enzyme.
AB  - The Arabidopsis FATTY ACID ELONGATION1 (FAE1) gene encodes a putative seed
      specific condensing enzyme. It is the first of four enzyme activities that
      comprise the microsomal fatty acid elongase (FAE) involved in the biosynthesis of
      very-long-chain fatty acids (VLCFAs). FAE1 has been expressed in yeast and in
      tissues of Arabidopsis and tobacco, where significant quantities of VLCFAs are
      not found. The introduction of FAE1 alone in these systems is sufficient for the
      production of VLCFAs, for wherever FAE1 was expressed, VLCFAs accumulated. These
      results indicate that FAE1 is the rate-limiting enzyme for VLCFA biosynthesis in
      Arabidopsis seed, because introduction of extra copies of FAE1 resulted in higher
      levels of the VLCFAs. Furthermore, the condensing enzyme is the activity of the
      elongase that determines the acyl chain length of the VLCFAs produced. In
      contrast, it appears that the other three enzyme activities of the elongase are
      found ubiquitously throughout the plant, are not rate-limiting and play no role
      in the control of VLCFA synthesis. The ability of yeast containing FAE1 to
      synthesize VLCFAs suggests that the expression and the acyl chain length
      specificity of the condensing enzyme, along with the apparent broad specificities
      of the other three FAE activities, may be a universal eukaryotic mechanism for
      regulating the amounts and acyl chain length of VLCFAs synthesized.

PMID- 9263456
TI  - Transformation of Arabidopsis thaliana with the codA gene for choline oxidase;
      accumulation of glycinebetaine and enhanced tolerance to salt and cold stress.
AB  - Glycinebetaine is one of the compatible solutes that accumulate in the
      chloroplasts of contain halotolerant plants when these plants are exposed to salt
      or cold stress. The codA gene for choline oxidase, the enzyme that converts
      choline into glycinebetaine, has previously been cloned from a soil bacterium,
      Arthrobacter globiformis. Transformation of Arabidopsis thaliana with the cloned
      codA gene under the control of the 35S promoter of cauliflower mosaic virus
      enabled the plant to accumulate glycinebetaine and enhanced its tolerance to salt
      and cold stress. At 300 mM NaCl, considerable proportions of seeds of transformed
      plants germinated well, whereas seeds of wild-type plants failed to germinate. At
      100 mM NaCl, transformed plants grew well whereas wild-type plants did not do so.
      The transformed plants tolerated 200 mM NaCl, which was lethal to wild-type
      plants. After plants had been incubated with 400 mM NaCl for two days, the
      photosystem II activity of wild-type plants had almost completely disappeared,
      whereas that of transformed plants remained at more than 50% of the original
      level. When exposed to a low temperature in the light, leaves of wild-type plants
      exhibited symptoms of chlorosis, whereas those of transformed plants did not.
      These observations demonstrate that the genetic modification of Arabidopsis
      thaliana that allowed it to accumulate glycinebetaine enhanced its ability to
      tolerate salt and cold stress.

PMID- 9263457
TI  - Spatial expression dynamics of Men-9 delineate the third floral whorl in male and
      female flowers of dioecious Silene latifolia.
AB  - Sex determination in Silene latifolia is controlled by heteromorphic sex
      chromosomes. Female flowers have five fused carpels and ten arrested stamen
      primordia. The male-determining Y chromosome overrides female development to
      suppress carpel formation and promote stamen development. The isolation and
      characterization of two S. latifolia. Male enhanced cDNAs, Men-9a and Men-9b,
      which probably represent different alleles of a novel gene are reported here. Men
      9a and Men-9b share 91.8% coding sequence nucleotide identity, yet only 85.4%
      amino acid identity. The Men-9 cDNAs are related to the previously reported MROS3
      cDNA from S. latifolia. However, MROS3 is not present in the S. latifolia
      population used in these studies and the expression dynamics of Men-9a and Men-9b
      contrast dramatically with those reported for MROS3. Men-9 cDNAs are expressed
      primarily in anthers of young male flowers, with highest expression in 1-2 mm
      buds. Men-9 expression is also observed at a low level in female flowers. In situ
      hybridization analysis reveals two phases of Men-9 expression. The first phase is
      during a common stage of early stamen development in male and female flowers
      prior to stamen arrest in female flowers. The second phase of Men-9 expression is
      maximal in the epidermis and endothecium of Y chromosome- and Ustilago violacea
      induced stamens; expression in male and female flowers extends to the epidermis
      of the staminal nectaries with strict boundaries at the second and fourth whorls,
      Men-9 gene expression therefore delineates the boundaries of the third floral
      whorl in S. latifolia flowers.

PMID- 9263458
TI  - Yeast 5-aminolevulinate synthase provides additional chlorophyll precursor in
      transgenic tobacco.
AB  - Synthesis of the tetrapyrrole precursor 5-aminolevulinate (ALA) in plants starts
      with glutamate and is a tRNA-dependent pathway consisting of three enzymatic
      steps localized in plastids. In animals and yeast, ALA is formed in a single step
      from succinyl CoA and glycine by aminolevulinate synthase (ALA-S) in
      mitochondria. A gene encoding a fusion protein of yeast ALA-S with an
      aminoterminal transit sequence for the small subunit of ribulose bisphosphate
      carboxylase was introduced into the genome of wild-type tobacco and a chlorophyll
      deficient transgenic line expressing glutamate 1-semi-aldehyde aminotransferase
      (GSA-AT) antisense RNA. Expression of ALA-S in the GSA-AT antisense transgenic
      line provided green-pigmented co-transformants similar to wild-type in
      chlorophyll content, while transformants derived from wild-type plants did not
      show phenotypical changes. The capacity to synthesize ALA and chlorophyll was
      increased in transformed plants, indicating a contribution of ALA-S to the ALA
      supply for chlorophyll synthesis. ALA-S activity was detected in plastids of the
      transformants. Preliminary evidence is presented that succinyl CoA, the substrate
      for ALA-S, can be synthesized and metabolized in plastids. The transgenic plants
      formed chlorophyll in the presence of gabaculine, an inhibitor of GSA-AT. Steady
      state RNA and protein levels and consequently, the enzyme activity of GSA-AT were
      reduced in plants expressing ALA-S. In analogy to the light-dependent ALA
      synthesis attributed to feedback regulation, a mechanism at the level of
      intermediates or tetrapyrrole end-products is proposed, which co-ordinates the
      need for heme and chlorophyll precursors and restricts synthesis of ALA by
      regulating GSA-AT gene expression. The genetically engineered tobacco plants
      containing the yeast ALA-S activity demonstrate functional complementation of the
      catalytic activity of the plant ALA-synthesizing pathway and open strategies for
      producing tolerance against inhibitors of the C5 pathway.

PMID- 9263459
TI  - The plant 2-Cys peroxiredoxin BAS1 is a nuclear-encoded chloroplast protein: its
      expressional regulation, phylogenetic origin, and implications for its specific
      physiological function in plants.
AB  - 2-Cys peroxiredoxins constitute a family of enzymes which catalyze the transfer
      of electrons from sulfhydryl residues to peroxides and are ubiquitously
      distributed among all organisms. This paper characterizes the higher plant 2-Cys
      peroxiredoxin BAS1. (i) Escherichia coli over-expressing BAS1 exhibit increased
      tolerance for alkyl hydroperoxides in vivo. This result substantiates the
      peroxiredoxin function of BAS1. (ii) BAS1 protein is associated with the soluble
      chloroplast fraction of mesophyll protoplasts. Import and processing of in vitro
      transcribed and cell-free translated BAS1 protein into isolated chloroplasts
      provides conclusive evidence that the plant-specific N-terminal extension of bas1
      encodes the chloroplast import signal which targets the pre-form of BAS1 to the
      chloroplast stroma where it is cleaved to its mature size. (iii) Genomic analysis
      reveals that the targeting signal is encoded by a separate exon in Arabidopsis
      thalina. (iv) The amino acid sequence of the BAS1 core protein of higher plants
      has a higher degree of similarity to open reading frames in the genome of the
      bluegreen algae Synechochystis PCC sp. 6803 and in the plastome of the red algae
      Porphyra purpurea than to any other nuclear-encoded 2-Cys peroxiredoxin.
      Therefore, it is tempting to speculate that the chloroplast import signal was
      added to an ancestor gene of endosymbiotic origin in the course of plant
      evolution. (v) The bas1 gene expression is regulated under the control of the
      cellular redox state which is in accordance with the anti-oxidant function of the
      enzyme. While oxidative stressors increased expression only slightly,
      antioxidants such as reduced thiols strongly suppressed the transcript level. The
      implications of these findings are discussed with respect to the possible
      physiological functions of BAS1.

PMID- 9263460
TI  - Roscovitine, a novel cyclin-dependent kinase inhibitor, characterizes restriction
      point and G2/M transition in tobacco BY-2 cell suspension.
AB  - Although the developmental programs of plants and animals differ, key regulatory
      components of their cell cycle have been conserved. Particular attention has been
      paid to the role of the complexes between highly conserved cyclin and cyclin
      dependent kinases in regulating progression through the cell cycle. The recent
      demonstration that roscovitine is a potent and selective inhibitor of the animal
      cyclin-dependent kinases cdc2 (CDK1), CDK2 and CDK5 prompted an investigation
      into its effects on progression through the plant cell cycle. Roscovitine induced
      arrests both in late G1 and late G2 phase in BY-2 tobacco cell suspensions. Both
      block were fully reversible when roscovitine was used at concentrations similar
      to those used in the animal system. Stationary-phase cells subcultured in the
      presence of roscovitine were arrested at a 2C DNA content. This arrest was more
      efficient without exogenous addition of plant growth regulator. Roscovitine
      induced a block in G1 earlier than that induced by aphidicolin. S-phase
      synchronized cells treated with roscovitine were arrested at a 4C DNA content at
      the G2/ M transition. The expression analysis of a mitotic cyclin (NTCYC1)
      indicated that the roscovitine-induced G2 block probably occurs in late G2.
      Finally, cells in metaphase were insensitive to roscovitine. The purified
      CDK/cyclin kinase activities of late G1 and early M arrested cells were inhibited
      in vitro by roscovitine. The implications of these experimental observations for
      the requirement for CDK activity during progression through the plant cell cycle
      are discussed.

PMID- 9263461
TI  - Alteration of anion channel kinetics in wild-type and abi1-1 transgenic Nicotiana
      benthamiana guard cells by abscisic acid.
AB  - The influence of the plant water-stress hormone abscisic acid (ABA) on anion
      channel activity and its interaction with protein kinase and phosphatase
      antagonists was examined in stomatal guard cells of wild-type Nicotiana
      benthamiana L. and of transgenic plants expressing the dominant-negative (mutant)
      Arabidopsis abi1-1 protein phosphatase. Intact guard cells were impaled with
      double-barrelled micro-electrodes and membrane current was recorded under voltage
      clamp in the presence of 15 mM CsCl and 15 mM tetraethylammonium chloride (TEA
      Cl) to eliminate K+ channel currents. Under these conditions, the free-running
      voltage was situated close to 0 mV (+9 +/- 6 mV, n = 18) and the membrane under
      voltage clamp was dominated by anion channel current (ICl) as indicated from tall
      current reversal near the expected chloride equilibrium potential, current
      sensitivity to the anion channel blockers 9-anthracene carboxylic acid and
      niflumic acid, and by its voltage-dependent kinetics. Pronounced activation of
      ICl was recorded on stepping from a conditioning voltage of -250 mV to voltages
      between -30 and +50 mV, and the current deactivated with a voltage-dependent
      halftime at more negative voltages (tau approximately equal to 0.3 sec at -150
      mV). Challenge with 20 microM ABA increased the steady-state current conductance,
      gCl, near 0 mV by 1.2- to 2.6-fold and at -150 mV by 4.5- to sixfold with a time
      constant of 40 +/- 4 sec, and it slowed ICl deactivation as much as fourfold at
      voltages near -50 mV, introducing two additional voltage-sensitive kinetic
      components to these current relaxations. Neither the steady-state and kinetic
      characteristics of ICl nor its sensitivity to ABA were influenced by H7 or
      staurosporine, both broad-range protein kinase antagonists. However, the protein
      phosphatase 1/2A antagonist calyculin A mimicked the effects of ABA on gCl and
      current relaxations on its own and exhibited a synergistic interaction with ABA,
      enhancing ICl sensitivity to ABA three- to four-fold. Quantitatively similar
      current characteristics were recorded from guard cells of abi1-1 transgenic N.
      benthamiana, indicating that the abi1-1 protein phosphatase does not influence
      the anion current or its response to ABA directly. These results demonstrate that
      ABA stimulates ICl and modulates its voltage sensitivity. Furthermore, they show
      that ABA promotes ICl, either by introducing additional long-lived states of the
      channel or by activating a second anion channel with similar permeation
      characteristics but with a very long dwell time in the open state. Overall, the
      data are broadly consistent with the view that ABA action engenders coordinate
      control of ICl together with guard cell K+ channels to effect solute loss and
      stomatal closure.

PMID- 9263462
TI  - Structure and subcellular localization of a small RNA-binding protein from
      tobacco.
AB  - In this study, a cDNA encoding a small RNA-binding protein was isolated from a
      Nicotiana sylvestris cDNA library. The predicted protein (RGP-3) is 144 amino
      acid residues long, and contains a consensus sequence-type RNA binding domain (CS
      RBD) of 83 amino acids and a short glycine-rich region of 15 amino acids. RGP-3
      synthesized in Escherichia coli has high affinity for poly(U). Immunocytochemical
      analysis indicated that RGP-3 is localized in the nucleoplasm, and that RGP-1b, a
      related protein reported previously, is localized in the nucleolus. Possible
      roles of these proteins in pre-mRNA or pre-rRNA processing are discussed.

PMID- 9263463
TI  - ZmEsr, a novel endosperm-specific gene expressed in a restricted region around
      the maize embryo.
AB  - A novel endosperm-specific gene named Esr (embryo surrounding region) has been
      isolated by differential display between early developmental stages of maize
      endosperms and embryos. It is expressed in a restricted region of the endosperm,
      surrounding the entire embryo at early stages (4 to 7 days after pollination,
      DAP) and ever-decreasing parts of the suspensor at subsequent stages. The
      expression starts at 4 DAP and is maintained until at least 28 DAP. A minimum of
      three Esr genes are present in the maize genome and at least two of them map to
      the short arm of chromosome 1 at position 56. The Esr genes contain no introns
      and show no significant nucleotide or amino acid sequence homologies to sequences
      in the databases. The open reading frames encode basic proteins of 14 kDa with
      presumptive signal peptides at their N-terminal followed by a hypervariable and a
      conserved region. The gene product may play a role in the nutrition of the
      developing embryo or in the establishment of a physical barrier between embryo
      and endosperm.

PMID- 9263464
TI  - Who mixes with whom? A method to determine the contact patterns of adults that
      may lead to the spread of airborne infections.
AB  - Although mixing patterns are thought to be important determinants of the spread
      of airborne infectious diseases, to our knowledge, there have been no attempts to
      directly quantify them for humans. We report on a preliminary study to identify
      such mixing patterns. A sample of 92 adults were asked to detail the individuals
      with whom they had conversed over the period of one, randomly assigned, day.
      Sixty-five (71%) completed the questionnaire, providing their age, the age of
      their contacts and the social context in which the contacts took place. The data
      were analysed using multilevel modelling. The study identified, and allowed the
      quantification of, contact patterns within this sample that may be of
      epidemiological significance. For example, the degree of assortativeness of
      mixing with respect to age was dependent not only on the age of participants but
      the number of contacts made. Estimates of the relative magnitude of contact rates
      between different social settings were made, with implications for outbreak
      potential. Simple questionnaire modifications are suggested which would yield
      information on the structure and dynamics of social networks and the intensity of
      contacts. Surveys of this nature may enable the quantification of who acquires
      infection from whom and from where.

PMID- 9263466
TI  - Dominance and queen succession in captive colonies of the eusocial naked mole
      rat, Heterocephalus glaber.
AB  - Naked mole-rat colonies exhibit a high reproductive skew, breeding being
      typically restricted to one female (the 'queen') and one to three males. Other
      colony members are reproductively suppressed, although this suppression can be
      reversed following the removal or death of the queen. We examined dominance and
      queen succession within captive colonies to investigate the relationship between
      urinary testosterone and cortisol, dominance rank and reproductive status; and to
      determine if behavioural and/or physiological parameters can be used as
      predictors of queen succession. Social structure was characterized by a linear
      dominance hierarchy before and after queen removal. Prior to queen removal,
      dominance rank was negatively correlated with body weight and urinary
      testosterone and cortisol titres in males and females. Queen removal results in
      social instability and aggression between high ranking individuals. Dominance
      rank appears to be a good predictor of reproductive status: queens are the
      highest ranking colony females and are succeeded by the next highest ranking
      females. The intense dominance-related aggression that accompanies reproductive
      succession in naked mole-rats provides empirical support for optimal skew theory.

PMID- 9263465
TI  - Optimal killing for obligate killers: the evolution of life histories and
      virulence of semelparous parasites.
AB  - Many viral, bacterial and protozoan parasites of invertebrates first propagate
      inside their host without releasing any transmission stages and then kill their
      host to release all transmission stages at once. Life history and the evolution
      of virulence of these obligately killing parasites are modelled, assuming that
      within-host growth is density dependent. We find that the parasite should kill
      the host when its per capita growth rate falls to the level of the host mortality
      rate. The parasite should kill its host later when the carrying capacity, K, is
      higher, but should kill it earlier when the parasite-independent host mortality
      increases or when the parasite has a higher birth rate. When K(t), for parasite
      growth, is not constant over the duration of an infection, but increases with
      time, the parasite should kill the host around the stage when the growth rate of
      the carrying capacity decelerates strongly. In case that K(t) relates to host
      body size, this deceleration in growth is around host maturation.

PMID- 9263467
TI  - LH responses to single doses of exogenous GnRH by social Mashona mole-rats: a
      continuum of socially induced infertility in the family Bathyergidae.
AB  - The Mashona mole-rat, Cryptomys darlingi, exhibits an extreme reproductive
      division of labour. Reproduction in the colony is restricted to a single breeding
      pair. The non-reproductive male and female colony members are restrained from
      sexual activity by being familiar and related to one another and the reproductive
      animals. Circulating basal concentrations of luteinizing hormone (LH) as well as
      LH levels measured in response to a single exogenous gonadotropin releasing
      hormone (GnRH) challenge are not significantly different between the reproductive
      and non-reproductive groups of either sex. Socially induced infertility in both
      non-reproductive males and females does not result from a reduced pituitary
      secretion of LH or decreased sensitivity to hypothalamic GnRH, but rather appears
      to result from an inhibition of reproductive behaviour in these obligate
      outbreeders. The African mole-rats exhibit a continuum of socially induced
      infertility with differing social species inhabiting regions of varying degrees
      of aridity. In this continuum a transition from a predominantly behavioural
      repression in a social mesic-adapted species through to complete physiological
      suppression lacking incest avoidance in an arid-adapted eusocial species occurs
      in this endemic African family of rodents.

PMID- 9263468
TI  - Synaesthesia in the normal limb.
AB  - We explored the degree to which vision may alter kinaesthetic perception by
      asking participants to view their hand through a prism, introducing different
      horizontal deviations, while trying to align their fingers above and below a thin
      table. When the visual image of one hand was displaced this overwhelmed
      kinaesthetic judgements and participants reliably reported that they felt their
      limbs were aligned, even when they were laterally mis-aligned by as much as 10
      cm. This effect, however, was mediated by 'visual capture' and when the task was
      attempted in a darkened room with limb position indicated by an LED taped to the
      finger, kinaesthesis dominated and participants reported that the LED seemed to
      become detached from their finger tip. In both light and dark conditions the
      finger was clearly visible and only the background detail was extinguished.
      Hence, in perceiving limb position, it appears that we believe in what we see,
      rather than in what we feel, when the visual background is rich, and in what we
      feel when the visual background is sparse.

PMID- 9263469
TI  - Reconstructing labroid evolution with single-copy nuclear DNA.
AB  - Fifteen per cent of all living fishes are united in a single suborder (Labroidei)
      and display a dazzling array of behavioural and ecological traits. The labroids
      are considered monophyletic and members share a pharyngeal jaw apparatus (PJA)
      modified for crushing and processing prey. Outside of the explicitly functional
      PJA, there is no corroborative evidence for a monophyletic Labroidei. Here, we
      report the first molecular phylogenetic analysis of the suborder. Contrary to
      morphology-based phylogenies, our single-copy nuclear DNA data do not support
      labroid families as a natural group. Our data indicate that pharyngognathy has
      evolved independently among labroid families and that characters of the PJA are
      not reliable markers of perciform evolution. This work 'crushes' conventional
      views of fish phylogeny and should engender novel concepts of piscine life
      history evolution.

PMID- 9263470
TI  - The role of visual field position in pattern-discrimination learning.
AB  - Invariance of object recognition to translation in the visual field is a
      fundamental property of human pattern vision. In three experiments we
      investigated this capability by training subjects to distinguish between random
      checkerboard stimuli. We show that the improvement of discrimination performance
      does not transfer across the visual field if learning is restricted to a
      particular location in the retinal image. Accuracy after retinal translation
      shows no sign of decay over time and remains at the same level it had at the
      beginning of the training. It is suggested that in two-dimensional translation
      invariance-as in three-dimensional rotation invariance-the human visual system is
      relying on memory-intensive rather than computation-intensive processes. Multiple
      position- and stimulus-specific learning events may be required before
      recognition is independent of retinal location.

PMID- 9263471
TI  - Molecular evidence for single Wolbachia infections among geographic strains of
      the flour beetle Tribolium confusum.
AB  - Infections with the rickettsial microorganism Wolbachia are cytoplasmically
      inherited and occur in a wide range of insect species and several other
      arthropods. Wolbachia infection often results in unidirectional cytoplasmic
      incompatibility (CI): crosses between infected males and uninfected females are
      incompatible and show a reduction of progeny or complete inviability.
      Unidirectional CI can also occur when males harbouring two incompatible Wolbachia
      strains are crossed with females infected with only one of the two strains. In
      the flour beetle Tribolium confusum, Wolbachia infections are of particular
      interest because of the severity of incompatibility. Typically, no progeny
      results from the incompatible cross, whereas only partial incompatibility is
      observed in most other hosts. Werren et al. (1995a) reported that Wolbachia
      infections in T. confusum consist of two bacterial strains belonging to distinct
      phylogenic groups, based on PCR amplification and sequence analysis of the
      bacterial cell division gene ftsZ. However, Fialho & Stevens (1996) showed that
      eight strains of T. confusum were infected with a single and common
      incompatibility type. Here we report analysis of the ftsZ gene by specific PCR
      amplification. Diagnostic restriction enzyme assays revealed no evidence of
      double infections in 11 geographic strains of T. confusum, including the strain
      examined by Werren et al. (1995a). Further, sequence analysis of the Wolbachia
      ftsZ gene and an internal transcribed spacer (ITS) region in two of these strains
      displayed no nucleotide variation or evidence of polymorphisms. Results suggest
      that T. confusum is infected with B-group Wolbachia only.

PMID- 9263472
TI  - A model of bovine tuberculosis control in domesticated cattle herds.
AB  - A typical strategy for disease control in domesticated animals involves regular
      field tests and quarantine of infected herds. This prevents disease spread beyond
      the herd, while slaughter of diseased animals removes the infection from within
      the herd. A model of bovine tuberculosis (Tb) control in cattle is examined,
      which includes 'test and slaughter' combined with herd isolation and vaccination.
      Herd status is represented by an integral equation expressing the duration of
      herd isolation. The current Tb situation in New Zealand is used as an example,
      and vaccination strategy discussed. Extrapolation of existing management
      strategies indicate that a vaccine of efficacy greater than 96% would be
      required, reaching 95% of target Tb levels within six years. These results
      suggest that a complementary strategy of vaccination and vector control may be
      more promising than vaccination alone.

PMID- 9263473
TI  - Evolutionary relationships of the metazoan beta gamma-crystallins, including that
      from the marine sponge Geodia cydonium.
AB  - beta gamma-crystallins are one major component of vertebrate lenses. Here the
      isolation and characterization of a cDNA, coding for the first beta gamma
      crystallin molecule from an invertebrate species, the marine sponge Geodia
      cydonium, is described. The size of the transcript as determined by Northern
      blotting was 0.7 kb in length. The deduced amino acid sequence consists of 163 aa
      residues and comprises four repeated motifs which compose the two domains of the
      beta gamma-crystallin. Motif 3 contains the characteristic beta gamma-crystallin
      'Greek key' motif signature, while in each of the three other repeats, one aa
      residue is replaced by an aa with the same physico-chemical property. The sponge
      peptide shows striking similarities to vertebrate beta gamma-crystallins.
      Analysis by neighbour joining of the sponge motifs with the two motifs present in
      spherulin 3a of Physarum polycephalum shows that motif 4 of the sponge beta gamma
      crystallin was added as the last single sequence to the tree. The data support
      the view that the beta gamma-crystallin superfamily, present in eukaryotes,
      evolved from a common ancestor including also the sponge beta gamma-crystallin.

PMID- 9263475
TI  - Towards an oral influenza vaccine.

PMID- 9263474
TI  - Reduced autonomic responses to faces in Capgras delusion.
AB  - People experiencing the Capgras delusion claim that others, usually those quite
      close emotionally, have been replaced by near-identical impostors. Ellis & Young
      suggested in 1990 that the Capgras delusion results from damage to a neurological
      system involved in orienting responses to seen faces based on their personal
      significance. This hypothesis predicts that people suffering the Capgras delusion
      will be hyporesponsive to familiar faces. We tested this prediction in five
      people with Capgras delusion. Comparison data were obtained from five middle-aged
      members of the general public, and a psychiatric control group of five patients
      taking similar anti-psychotic medication. Capgras delusion patients did not
      reveal autonomic discrimination between familiar and unfamiliar faces, but
      orienting responses to auditory tones were normal in magnitude and rate of
      initial habituation, showing that the hyporesponsiveness is circumscribed.

PMID- 9263476
TI  - Transdermal therapy and diagnosis by iontophoresis.
AB  - Iontophoresis, the use of an electric current to drive charged molecules across
      the skin, has the potential to expand the feasible range of drugs for transdermal
      administration significantly. This method of delivery is being examined carefully
      with respect to higher-molecular-weight therapeutics (in particular, peptides and
      small proteins), which cannot be absorbed following oral administration and for
      which, at this time, an invasive injection remains the only option. In addition,
      the procedure of so-called 'reverse' iontophoresis would appear to represent a
      truly noninvasive approach for diagnostic monitoring of blood chemistry.

PMID- 9263477
TI  - Integration of foreign DNA and its consequences in mammalian systems.
AB  - The insertion of foreign DNA into the genomes of established cells and organisms
      and the consequences of this integration event are of significance for viral
      oncology, reverse genetics, transgenic organisms, human somatic gene therapy and
      evolution. This review summarizes recent experimental findings and focuses on the
      alteration of cellular DNA methylation at regions remote from the site of
      insertion. We also discuss experimental data demonstrating that foreign DNA
      ingested by mice is not completely degraded in their gastrointestinal tracts;
      fragments of this DNA have been found to be covalently linked to DNA with 70%
      homology to the mouse IgE receptor gene.

PMID- 9263478
TI  - Severe defects in immunity and hematopoiesis caused by SHP-1 protein-tyrosine
      phosphatase deficiency.
AB  - Spontaneous mouse mutations that cause severe immunodeficiency or autoimmunity
      are invaluable tools with which to investigate the mammalian immune system.
      Mutations at the 'motheaten' locus result in severe immunological dysfunction due
      to disruption of the structural gene encoding Src-homology 2-domain phosphatase-1
      (SHP-1). This natural model for a specific protein-tyrosine-phosphatase
      deficiency is being widely utilized to determine the role of SHP-1 in the
      negative regulation of multiple signaling pathways in a number of hematopoietic
      lineages.

PMID- 9263479
TI  - Heterologous biopharmaceutical protein expression in Streptomyces.
AB  - The commercial production of human proteins in recombinant microorganisms for
      therapeutic use is well established. Systems have been developed to exploit the
      natural ability of certain bacteria to secrete properly folded, bioactive
      proteins into the extracellular medium. The streptomycetes are a relatively well
      characterized group of nonpathogenic filamentous bacteria that have the capacity
      to secrete large amounts of protein. In particular, Streptomyces lividans has the
      ability to secrete human proteins at a commercially viable level, thanks to
      relatively well-established plasmid-based expression system, a high-biomass
      fermentation process and a low level of endogenous protease activity.

PMID- 9263480
TI  - Transgenic animals as models of neurodegenerative diseases in humans.
AB  - Neurodegenerative diseases are of major socioeconomic importance and represent an
      enormous challenge for the scientific and medical communities. Advances in
      molecular genetics during the past decade have begun to provide approaches for
      the establishment of animal models for these disorders using transgenic
      technology. Their analysis will lead to better understanding of disease
      pathogenesis and will be invaluable for the identification of novel diagnostic
      and therapeutic agents. With the current pace of genomic research, the generation
      of transgenic animal models, reproducing in full the pathology and symptoms of
      even complex disorders such as Alzheimer's disease, must now be considered
      achievable.

PMID- 9263481
TI  - Selective targeting of bioactive compounds to mitochondria.
AB  - Mitochondrial function can be manipulated selectively by targeting bioactive
      compounds to mitochondria in living cells. Current targeting mechanisms involve
      harnessing either the mitochondrial membrane potential or the mitochondrial
      protein-import machinery to take up molecules linked to lipophilic cations or
      mitochondrial signal peptides, respectively. Compounds localized like this have
      been used in studies of mitochondrial metabolism and show potential as anticancer
      drugs. In addition, because mitochondria play a role in many critical cell
      processes, mitochondrial targeting has the potential to protect, repair or kill
      cells selectively, and may become a key tool in the development of gene therapy
      for mitochondrial DNA diseases.

PMID- 9263482
TI  - The accessory root of the medial fascicle of the brachial plexus in man.
AB  - The continuation of the anterior division of the inferior trunk usually forms the
      medial fascicle. Sometimes the accessory root (2, 3, 10), derived from the middle
      trunk, takes part in its formation. Studies devoted to this root's internal
      structure have not been published yet, therefore I decided to work on some of its
      features. The study was performed on 264 medial fascicles obtained bilaterally
      from the cadavers of sixty one males and seventy one females who died between the
      first day and eighty seventh year of life. The methods used to visualize
      different structures of brachial plexus, to obtain and fix the sections, to stain
      the slides and to determine thickness of the examined parts of peripheral nervous
      system, number of fascicles, and the index of their cross-section area were
      described in the previous papers (9, 10).

PMID- 9263483
TI  - Roots of the lateral cord of the brachial plexus in man.

PMID- 9263484
TI  - Some features of the internal structure of the brachial plexus trunks in man.

PMID- 9263487
TI  - The influence of encortone on ultrastructural changes in the parotid cells of
      female white rats of Wistar race.
AB  - It is generally known that glucocorticoids exert an essential influence on
      digestive tract physiology (2). Many investigations carried out refer to the
      changes observed in the pancreas under different experimental conditions (4, 5,
      6, 7, 8). The investigations of the influence of glucocorticoids on salivary
      glands and mainly on a parotid gland are very general. Salivary glands play an
      important role in the initial stages of taking up and assimilating food.
      Moreover, the produced growth factors and parotin play an important role in
      tissue development and maturation in young animals (12).

PMID- 9263485
TI  - The roots and the trunk of the median nerve in man.

PMID- 9263486
TI  - Sinusogenous intracerebral inflammatory complications in CT-imaging.

PMID- 9263489
TI  - The high opening of the right bronchial artery with a non-typical course.
AB  - Authors describing the bronchial vessels agree to the fact that they are
      characterised by a great variability in regard to their number and the place
      where they leave aorta (1, 2, 6). The characteristic feature of the right
      bronchial artery is that it often forms common trunks with other vessels (mainly
      with the first right aortic intercostal branch or with one of the upper
      oesophageal arteries). It can also have a common let-out trunk with the left
      upper bronchial artery (4). Bearing in mind that the operations on trachea and
      bronchi are difficult, and that it is very important to maintain the blood supply
      of the walls in the operated organs we have decided to publish our observations.
      They refer to a case, not described before, in which the right bronchial artery
      left the aortic arch in a high position making the vascular supply to the front
      lower half of the trachea and its bifurcation. Then, it went down to the
      membranous part of the right bronchus.

PMID- 9263488
TI  - Impedance audiometry in newborns of abnormal deliveries.

PMID- 9263490
TI  - Ultrastructural study of odontoblasts of dental pulp in the cells aging process.
AB  - Odontoblasts located in the peripheral layer of the pulp reflect current state of
      the process connected with the formation of the secondary dentin and thereby they
      protect teeth from inflammatory processes (1, 3, 4, 6, 10). Odontoblasts are
      highly specialized cells that can react to the mechanical, thermic and toxic and
      bacterial traumas (12, 13, 14, 15).

PMID- 9263492
TI  - Maxillary fistulas of dental origin. The techniques of recognizing and supply.

PMID- 9263491
TI  - Histological examinations of the influence of 6-hydroxydopamine (6-OH-DA) upon
      the ileum of the guinea pig.
AB  - Examinations of the influence of 6-OH-DA (6-hydroxydopamine) upon the structure
      of nerve cells and their axons have been conducted by many authors and in various
      aspects (1, 2, 8, 10). They have concerned histochemistry, fluorescence and
      ultrastructure of neurons and have shown that the substance evokes various
      changes in the perikaryons and axons of adrenergic neurons. The wall of the small
      intestine is innervated by external autonomyous nerves and fibres of the
      intramural autonomyous plexuses. External autonomyous fibres make numerous
      anastomoses with the neurons of the two intramural plexuses and ganglia: the
      myenteric one (Auerbach's) and the submucosal one (Meissner's) (6). Both ganglia
      run along the length of the intestine and their neurons apart from making
      anastomoses, send axons to the nonstrained muscles cells and glandular cells in
      the mucosa. As a consequence, the active phase is easily carried over along the
      alimentary system stimulating action of nonstrained muscles and glandular cells.
      6-OH-DA exerts strong action upon the nerve cells and ends, that is why we have
      decided to examine the changes taking place in the ileum when the substance
      starts to operate.

PMID- 9263493
TI  - Ultrasonographic and tomographic evaluation of the chronic liver diseases.

PMID- 9263494
TI  - Effect of tumor necrosis factor alpha on steroidogenesis in cultured human
      ovarian granulosa cells.

PMID- 9263495
TI  - Brain neoplasms with development similar to transient brain ischaemia.
AB  - Diagnostics of brain tumours still remains a serious problem in neurologist's
      career. Difficulties in proper diagnosing refer mainly to endocranial tumours
      with atypical clinical course. Frequency of brain tumours' vascular manifestation
      is assessed as 1-4%, and in most cases it is the kind of manifestation which
      corresponds with intracerebral bleedings and more seldom with ischaemic strokes.
      Reports on brain tumours with developments similar to transient brain ischaemia
      (1, 2, 3, 4) are published occasionally. In Neurology Clinic of the Medical
      Academy in Lublin, we conducted observation of two patients with brain tumours
      (one metastatic and the other one-primary), where the former as well as the
      latter case were treated as cerebral circulation failures at their initial stage.
      Application of typical vasoactive treatment brought about temporary regression of
      symptoms.

PMID- 9263497
TI  - Current opinions in etiopathogenesis of headaches caused by cervical spine
      pathology.
AB  - Headaches of occipital and nape region, which repeat paroxysmally and are
      concerned with cervical spine disorders cause many problems in everyday medical
      practice. This review article presents problems of classification, clinical
      features and current opinions in etiopathogenesis of headaches caused by cervical
      spine pathology.

PMID- 9263499
TI  - The effect of intravenous loading with glucose on inorganic phosphorus and lipid
      phosphorus in the blood of patients with intracerebral haemorrhage.

PMID- 9263496
TI  - The influence of Nootropil on the content of inorganic phosphorus and lipid
      phosphorus in the blood of patients with intracerebral haemorrhage.
AB  - Nootropil exerts positive impact on both intracortical and cortico-subcortical
      conduction and increases ATP content in the nerve cell which leads to the
      increase of ribonucleic acid's synthesis necessary for long duration memory and
      proteins essential for the production of enzymes (3). The cerebral stroke can
      change the activity of the central vegetative neurons and induce generalized
      disturbances of the mechanism of metabolism, e. g. in phosphorus and phospholipid
      economy (1, 2).

PMID- 9263498
TI  - Does a spasm of vertebral canal exist?
AB  - During myelographic examination the travel of a contrast medium through the
      vertebral canal can be observed when it is applied by the lumbar puncture. When
      the vertebral canal is totally obstructed the contrast medium stops at the verge
      of the closing forming sometimes (in case of tumours) concave meniscus. In case
      of incomplete block of the canal the contrast medium flows around the obstacle.
      Results of myelographic examination do not leave much room for doubts as to the
      character of discovered disease process. They are very often confirmed during
      follow up computer tomography imaging of the suitable segment of the spinal
      column. In some patients being under clinical observation in this Department of
      Neurology, however, it was difficult to arrive at a specific diagnosis on the
      basis of the examination of their vertebral canal by means of the contrast medium
      in spite of the abnormalities observed repeatably and the concomitant severe
      progressive lessions of their spinal cords.

PMID- 9263500
TI  - Phosphorus economy in a healthy man.

PMID- 9263501
TI  - The types of renal calyces and pelvises in people from the Lublin region.

PMID- 9263502
TI  - Evaluation of the usefulness of the serum estriol (E3) estimation in preterm
      delivery.

PMID- 9263503
TI  - The estimation of progesterone (P) in preterm delivery.

PMID- 9263504
TI  - Ultrasonographic diagnostics of maxillo-facial haemangiomas.

PMID- 9263506
TI  - The value of behavioral methods of hearing examinations in comparison with ABR.

PMID- 9263505
TI  - Morphological and biochemical studies of daunorubicin hepatotoxicity including
      the protective effects of tocopherol and ascorbic acid.

PMID- 9263507
TI  - Thiamine blood level and erythrocyte transketolase activity in continuous
      ambulatory peritoneal dialysis and intermittent peritoneal dialysis patients.

PMID- 9263508
TI  - Dental amalgam and antibiotic resistance--an association?

PMID- 9263509
TI  - Neurological gene therapy.

PMID- 9263510
TI  - Adaptive mutations: a challenge to neo-Darwinism?

PMID- 9263511
TI  - Perfluorochemical respiratory gas carriers: applications in medicine and
      biotechnology.

PMID- 9263512
TI  - [Malignancy of colorectal cancer analyzed by expression of cyclin D1].
AB  - We evaluated the clinical significance of cyclin D1 expression in colorectal
      adenocarcinoma. One hundred twenty-three specimens resected from patients with
      colorectal cancers were investigated by staining with a monoclonal antibody
      against cyclin D1. The possible correlations among cyclin D1 expression,
      clinicopathologic factors and prognosis were studied. There was no significant
      association between cyclin D1 expression and various clinicopathological factors.
      However, disease-free survival was significantly worse in the patients with
      cyclin D1 strongly positive tumors than in those with cyclin D1 negative tumors.
      Cyclin D1 overexpression may be useful as a predictor of disease recurrence in
      patients with colorectal adenocarcinoma.

PMID- 9263513
TI  - [p53 alterations and chromosome 17 aberrations in non-small cell lung cancer].
AB  - We studied the relationship between DNA index, numerical abberation of chromosome
      17 and alterations of the p53 gene in 23 non-small cell lung cancers. Diploid and
      aneuploid cells from 23 non-small cell lung cancer with DNA aneuploidy were flow
      sorted into each cell population using FACStar(plus). They were examined by PCR
      SSCP analysis for p53 mutation and by microsatellite analysis for loss of
      heterozygosity at TP53 locus (17p13.1). They were also analyzed by FISH for copy
      number of chromosome 17. p53 mutations were found in aneuploid cells from the 11
      cases (48%). Among them, 8 cases were informative at TP53 locus, and all showed
      loss of heterozygosity. Aneuploid cells from 16 cases exhibited gain of
      chromosome 17 copy number in FISH analysis. DNA index was significantly
      associated with th mean copy number of chromosome 17, suggesting that the number
      of chromosome 17 changed with DNA index. There were no associations between p53
      mutation and DNA index or mean copy number of chromosome 17. In some cases, we
      also analyzed structural abberation of short arm of chromosome 17 by FISH using
      p53-cosmid (17p13.1) and Distal 17p (17p13.3-ptel) probes. The p53 gene located
      on the increased chromosome 17 was lost due to point mutation or deletion of 17p.

PMID- 9263515
TI  - [Analysis of microsatellite regions and DNA ploidy pattern in signet ring cell
      carcinomas of the stomach].
AB  - We examined microsatellite instability (MSI) and loss of heterozygosity (LOH) in
      regions of several important genes in 25 signet-ring cell carcinomas of the
      stomach. The relationship between microsatellite analysis and DNA ploidy pattern
      was also investigated. MSI was observed in 15% (2/13) of early carcinomas and in
      17% (2/12) of advanced carcinomas. Although LOH in the region of APC gene was
      found in 16% (4/25) and LOH of p53 was found in 12% (3/25), 15% (2/13) of early
      carcinomas and 33% (4/12) of advanced carcinomas showed LOH in regions of E
      cadherin gene. Cyto-fluorometrical study revealed that 85% (11/13) of early
      carcinomas were diploid pattern, and aneuploid components were demonstrated in
      50% (6/12) of advanced carcinomas. However, no MSI-positive cases contained
      aneuploid components, and in contrast, all p53-LOH cases contained aneuploid
      components. Our results suggest that gene abnormalities which have been
      frequently reported in differentiated adenocarcinomas are rare events in signet
      ring cell carcinomas other than those associated with cell adhesion, and that MSI
      is not related to the occurrence of aneuploid cells.

PMID- 9263514
TI  - [Clinicopathological study on early recurrent hepatoma and its treatment].
AB  - Early Recurrence of Hepatoma: PCNA Labeling Index and DNA Ploidy Pattern Sixty
      four cases of recurrent hepatocellular carcinoma (HCC) after hepatectomy were
      divided into two groups; E-group with recurrence within one year, and L-group
      with recurrence after 1 year. Clinicopathological features and surgical
      curability were the same in both groups. E-group had significantly higher
      positive rates of portal invasion, intrahepatic metastasis and rate of patients
      with more than 40% on PCNA labeling index. While the similar recurrence mode and
      the same treatment modalities were done, cumulative survival rates after
      recurrence in E-group had a poorer prognosis than L-group. These results suggest
      the possibility of lower response for the treatment on the recurrent lesion would
      be manifest in the E-group. New modalities for prevention of early recurrence of
      HCC after resection should be developed.

PMID- 9263516
TI  - [Alteration of p15 and p16 gene in gastric cancer].
AB  - We analyzed p15 and p16 gene alterations in gastric cancer. Only MKN45 showed
      both homozygous deletions but other cell lines and all of tumor specimens did not
      show any alterations. Using RT-PCR analysis, decreased or no expression of the
      p16 gene was found in 1 of 7 cell lines (except MKN45) (14.2%) and in 8 of 20
      tumors (40%), whereas no abnormalities of p15 gene expression were found. These
      results suggest that the p16 gene may correlate with tumorigenesis and tumor
      expansion due to decrease or loss of gene products in gastric cancer.

PMID- 9263517
TI  - [The significance of p21 expression in gastric cancer].
AB  - We examined the expression of p53, p21, cyclin D1, E, and PCNA in 75 cases of
      gastric cancer by immunohistochemical study and the expression of p21 RNA in
      cases by in situ hybridization. The rate of stage III, IV cases of p53(+) p21(-)
      group was significantly higher than that of any other groups. The apportinately 3
      year survival rate of p53(+) p21(-) group was significantly lower than either
      that of p21(+) p53(-) or p53(-) p21(-) group. The 3-year survival rates of
      positive cases were significantly lower than those of negative cases on both
      cyclin D1 and E. The positive rate of cyclin E of the p53(-) p21(+) group was
      significantly lower than that of the p53(+) p21(-) group. The average PCNA
      Labeling. Index (LI) of the p53(+) p21(-) group was significantly higher than
      that of the p53(-) p21(+) group. The 3-year survival rate of cases with
      expression of p21 RNA was higher than that of cases without p21 RNA. Average PCNA
      L1 of cases with expression of mutant-type p53 was high and the number of poor
      prognostic cases in cases with expression of mutant-type p53 was large. In
      contrast, the average PCNA LI of cases with expression of p21 was low and the
      number of good prognostic cases with expression of p21 was large. These results
      suggest that p21 suppresses synthesis of DNA via cyclin E and PCNA.

PMID- 9263518
TI  - [Immunohistochemical study of p21 expression in gastric carcinoma].
AB  - In this study, the expression of p21 protein was investigated
      immunohistochemically in 152 patients with gastric cancer. Expression of p21 was
      detected in 64 tumors (42.1%). There were significant differences among the
      expression of p21, histologic type, depth of invasion, lymph node metastasis,
      liver metastasis, and peritoneal metastasis. The deeper the tumor invaded, the
      more frequent p21 expression increased. Of the 152 patients, lymph node, liver
      and peritoneal metastasis were found in 86, 13 and 23 patients, respectively. p21
      expression was more frequently lost in tumors from patients with metastasis. In
      relation to prognosis, patients with p21-positive tumors had a significantly
      better prognosis than those with p21-negative tumors. In conclusion, this study
      suggested that expression of p21 has a prognostic value in gastric cancer.

PMID- 9263519
TI  - [Mechanism of regression of metastatic liver tumors in rats treated with
      angiogenesis inhibitor with special reference to apoptosis].
AB  - We examined the mechanism of the reduction of metastatic liver tumors in rats
      treated with angiogenesis inhibitor TNP-470 on the histological basis of patterns
      of tumor cell death. Metastatic tumors were developed by intravenous injection of
      AH-130 cell line, followed by a dose of TNP-470. Alteration in the size and
      number of metastatic liver tumors and its cell death pattern were analyzed. The
      number and size of the metastatic tumors at 2 weeks in untreated rats were larger
      than those in treated rats. The number of tumors in untreated rats decreased,
      whereas their size increased. All rats treated were alive and free from tumors
      after 4 weeks, although all untreated rats died of metastatic tumors. Necrosis
      was predominant in the tumors of untreated rats, while most tumors in treated
      rats showed apoptosis. Consequently, the metastatic tumor in untreated rats might
      grow faster than its angiogenesis, suggesting the occurrence of central necrosis
      due to apparent ischemia. On the other hand, the tumor in treated rats might be
      reduce a by weak ischemic stimulus, which triggers apoptosis.

PMID- 9263520
TI  - [Correlations between cell proliferating activity and apoptosis in the colorectal
      cancer and apoptosis in the mucosa adjacent to colorectal cancer].
AB  - To investigate the growth and progression of colorectal cancer, cell production
      versus cell loss in colorectal cancer was examined using the proliferating cell
      nuclear antigen (PCNA) positivity rate and apoptotic index (AI). Cell loss was
      then examined using AI in the mucosa adjacent to colorectal cancer. The higher
      the PCNA positivity rate, the higher the apoptotic index in colorectal cancer.
      These results suggested that changes in cell production and cell loss may be
      closely correlated and play a role in the growth and progression of colorectal
      cancer. In patients with advanced colorectal cancer, the mucous composition of
      the adjacent mucosa was classified as sialomucin-predominant. Apoptosis at the
      proliferating zone in the mucosa adjacent to colorectal cancer (one or two
      glandular ducts) was also examined using the TUNEL method. This suggests that the
      mucosa adjacent to cancer is involved in apoptosis.

PMID- 9263521
TI  - [Minute carcinoid tumor in the rectum with liver metastasis].
AB  - A 65-year-old woman was admitted to our hospital for evaluation of multiple liver
      tumors following endoscopic polypectomy for rectal polyp a year earlier. The
      polypectomy specimen was reexamined and showed inclusion of a carcinoid tumor 3
      mm in diameter. The perirectal lymph node was palpated by digital examination on
      readmission. The patient died one mouth after readmission due to liver failure.
      Autopsy revealed metastatic carcinoid tumor in the liver and perirectal nodes.

PMID- 9263522
TI  - [Prognosis of renal cell carcinoma and detection of numerical chromosome
      aberration].
AB  - Identification of numerical abberations of chromosome #3, #7, #11, #17, #18, X
      and Y were evaluated using biotinylated probes specific for the alpha satellite
      region on paraffin embedded sections from formalin-fixed materials of renal cell
      carcinoma utilizing in situ hybridization (ISH). The copy number of each
      chromosome did not show any correlation with tumor grade, clinical (Robson)
      stage, pT, pN, pV or the presence of metastasis. Copy numbers of #3 chromosome
      were highly correlated with the patient prognosis (p < 0.01). Since numerical
      abberations of #3 chromosome are suggested to be correlated with the prognosis of
      renal cell carcinoma, this technique can now be applied to the detection of
      biological activity in renal cell carcinoma.

PMID- 9263523
TI  - [Analysis of DNA ploidy pattern and overexpression of p53 protein in cases of
      early gastric carcinoma with lymph node metastasis].
AB  - Twenty-one cases of surgically resected early gastric carcinoma with lymph nodal
      involvement (4 mucosal and 17 submucosal carcinomas) and 37 cases of that with no
      lymph nodal involvement (14 mucosal and 23 submucosal) were investigated by means
      of flow cytometry and immunohistochemical staining in order to clarify the
      correlation between lymph node metastasis and DNA ploidy pattern as well as
      overexpression of p53 protein. DNA aneuploidy was found to show a significantly
      higher frequency in submucosal carcinomas (60.0%) than in mucosal ones (22.2%),
      and also a significantly higher frequency in node positive cases (76.2%) than in
      node negative ones (32.4%). Meanwhile, the overexpression of p53 protein showed
      higher frequency in submucosal carcinomas (52.5%) than in mucosal ones (22.2%),
      and also higher frequency in node positive cases (47.6%) compared with that in
      node negative ones (40.5%). However there was no significant difference either in
      relation to the depth of tumor invasion or the lymph node metastasis. Thus, DNA
      aneuploidy showed a significant correlation to the depth of cancer invasion as
      well as lymph node metastasis, which was regarded as a useful indicator for the
      preoperative estimation of the depth of tumor invasion as well as lymph node
      metastasis.

PMID- 9263524
TI  - [Significance in gene expression of matrix metalloproteinase-9, urokinase-type
      plasminogen activator and tissue inhibitor of metalloproteinase for metastases of
      gastric and/or colo-rectal cancer].
AB  - In order to clarify the role of matrix metalloproteinase-9 (MMP-9), urokinase
      type plasminogen activator (uPA) and tissue inhibitor of metalloproteinase (TIMP)
      in metastases of gastroenterological cancer, their gene expression in the primary
      lesions on 47 gastric or 48 colorectal cancer patients was examined by RT-PCR
      method. 1) The expression of MMP-9, uPA, and TIMP was observed in 55.3%, 66.0%
      and 87.2% of gastric cancer and in 54.2%, 70.8%, and 89.6% of colorectal cancer,
      respectively. 2) In the cases with either peritoneal dissemination or lymph node
      metastases, the incidence of gene expression of MMP-9 was significantly higher in
      comparison to the cases without those metastases. The same result was observed as
      for uPA. 3) In the cases with liver metastases, the incidence of gene expression
      of MMP-9 was significantly higher in comparison to the cases without liver
      metastasis. The same result was observed as for uPA. The above results indicate
      that MMP-9 and uPA might play important roles in the peritoneal and lymph node
      metastases in gastric cancer and in liver metastasis in colorectal cancer.
      Therefore the investigation of their gene expression in the primary lesions of
      cancer could be one of the useful methods for the prediction of metastasis,
      leading to the best decision as to the treatment.

PMID- 9263525
TI  - [Findings of genetic changes in small intestinal carcinomas].
AB  - There is now good evidence that a series of genetic lesions in both dominant
      oncogenes and tumor suppressor genes are involved in the pathogenesis of human
      digestive tract carcinomas. Small intestinal carcinomas are very rare, accounting
      for only about 0.19% of all primary gastrointestinal malignant tumors in Japan,
      so there are few reports investigating genetic changes of small intestinal
      carcinoma. We analyzed 3 microsatellite loci and the status of K-ras and p53
      genes isolated from tumors and surrounding normal tissue samples obtained during
      surgery. The polymerase chain reaction (PCR) technique used frequent genetic
      instability to assess differences between tumor and matched DNAs. Replication
      errors (RERs) were observed in 3 of the 29 cases (10%) of gastric carcinoma and
      in 11 of the 72 cases (15%) of colorectal carcinoma. None of the 13 (0%)
      esophageal carcinoma cases showed any RER, but 5 of 11 cases of small intestinal
      carcinoma (45%) had RERs, reflecting a significantly high incidence. None of the
      11 small intestinal carcinoma cases exhibited K-ras gene mutations. Of 7 case
      amplified successfully by polymerase chain reaction (PCR) in exon 5-8 loci in p53
      gene, 2 exhibited abnormally migrated bands in polymerase chain reaction-single
      strand conformation polymorphism (PCR-SSCP) analysis. It is thus clear that the
      genetic carcinogenesis in the small intestine is different from other parts of
      the digestive tract. These results suggest that genetic instability plays an
      important role in the pathogenesis of small intestinal carcinomas.

PMID- 9263526
TI  - AML1 gene in human leukemias: dominant negative effects of the chimeric proteins
      over wild-type AML1.

PMID- 9263527
TI  - Inhibition of azoxymethane-initiated colon tumor by bovine lactoferrin
      administration in F344 rats.
AB  - The influence of bovine lactoferrin (bLF) on colon carcinogenesis was
      investigated in male F344 rats treated with azoxymethane (AOM). Following three
      weekly injections of AOM, the animals received 2 or 0.2% bLF for 36 weeks. No
      effects indicative of toxicity were noted, but significant reduction in both the
      incidence and number of adenocarcinomas of the large intestine was observed with
      both doses. Thus, the incidences of adenocarcinomas in the groups receiving 2%
      and 0.2% bLF were 15% and 25%, respectively, in contrast to the 57.5% control
      value (P < 0.01 and P < 0.05, respectively). The results indicate that bLF might
      find application for chemoprevention of colon cancer.

PMID- 9263528
TI  - A novel somatic mutation in the RET proto-oncogene in familial medullary thyroid
      carcinoma with a germline codon 768 mutation.
AB  - In individuals who carry germline mutations in tumor suppressor genes
      predisposing them to inherited cancer syndromes, occurrence of somatic mutations
      in the same genes contributes to tumorigenesis. Germline mutations in the RET
      proto-oncogene predispose individuals to multiple endocrine neoplasia (MEN) type
      2 syndromes. Since these mutations are oncogenic by themselves, somatic mutations
      in the same gene had been thought unnecessary. Recently, a somatic mutation at
      codon 918 of RET was reported in medullary thyroid carcinoma (MTC) and C-cell
      hyperplasia in patients with MEN 2A or familial MTC (FMTC), suggesting its
      possible contribution to tumorigenesis. We describe here a novel somatic mutation
      at codon 919 in a patient with FMTC carrying a germline mutation at codon 768
      that may also be related to tumor progression.

PMID- 9263530
TI  - Second primary cancers following non-Hodgkin's lymphoma in Japan: increased risk
      of hepatocellular carcinoma.
AB  - We evaluated the risk of development of second primary cancers, with particular
      reference to subsequent hepatocellular carcinoma (HCC), in 592 patients diagnosed
      as non-Hodgkin's lymphoma (NHL), at Osaka Medical Center for Cancer and
      Cardiovascular Diseases. During 1978-1994, 2,163 person-years of observation were
      accrued, and 27 of the patients developed a second primary cancer, yielding an
      observed-to-expected ratio (O/E) of 1.53 [95% confidence interval (CI) = 1.01
      2.23]. Significant excess risk was noted for primary liver cancer (PLC; O/E =
      4.36, 95% CI = 1.99-8.28; O = 9) and non-lymphocytic leukemia (O/E = 26.17, 95%
      CI = 5.26-76.46; O = 3). The excess risk of PLC was relatively constant within
      the first 10 years after the NHL diagnosis. Patients who received chemotherapy as
      the NHL treatment had a significantly increased risk of PLC (O/E = 5.91, 95% CI =
      2.70-11.23; O = 9). Their clinical reports indicated that all nine patients with
      PLC were diagnosed as HCC, and eight of them had clinical and/or histologic
      evidence of cirrhosis at the time of HCC diagnosis. None of the nine patients had
      a history of blood transfusion between the first NHL treatment and the diagnosis
      of HCC. These findings suggested that Japanese NHL patients might have an
      increased risk of developing HCC, and they indicated the importance of medical
      surveillance for liver malignancies, as well as subsequent leukemias. Possible
      explanations for the excess risk of subsequent HCC are discussed.

PMID- 9263529
TI  - Cytotoxin genes of Helicobacter pylori in chronic gastritis, gastroduodenal ulcer
      and gastric cancer: an age and gender matched case-control study.
AB  - Helicobacter pylori (H. pylori) infection is involved in many gastrointestinal
      diseases, such as chronic gastritis (CAG), peptic ulcer and gastric cancer (GCA).
      Both host factors and H. pylori strain differences may contribute to differences
      in the diseases. Thus, we conducted an age and gender matched case-control study
      of 35 patients each with CAG, gastric ulcer (GUL), duodenal ulcer (DUL) and
      gastric cancer (GCA) to examine the role of strain differences of the H. pylori
      cytotoxin genes cagA and vacA in these diseases. We employed polymerase chain
      reaction to examine the gastric juice for H. pylori DNA. The test was positive
      for 26 (74.3%) CAG, 29 (82.9%) GUL, 28 (80.0%) DUL and 27 (77.1%) GCA patients,
      showing no statistically significant difference among the diseases (P = 0.84).
      cagA and vacA genes (picked up by using a vacA1 + vacA2 primer pair which
      detected non-variable regions of the vacA gene) were detected by PCR in the H.
      pylori DNA-positive cases as follows: CAG, 92.3% and 76.9%; GUL, 100% and 86.2%;
      DUL, 89.3% and 89.3%; GCA, 92.6% and 85.2%, respectively. No statistically
      significant differences were found in the frequencies of these cytotoxin genes in
      H. pylori-positive cases among the various gastric diseases (P = 0.39 for cagA
      and P = 0.64 for vacA).

PMID- 9263531
TI  - Chemopreventive efficacy of piroxicam administered alone or in combination with
      lycopene and beta-carotene on the development of rat urinary bladder carcinoma
      after N-butyl-N-(4-hydroxybutyl)nitrosamine treatment.
AB  - The effects of the non-steroidal anti-inflammatory drug (NSAID) piroxicam and the
      carotenoids lycopene and beta-carotene, alone or in combination, on the
      development of rat superficial urinary bladder carcinomas induced by N-butyl-N-(4
      hydroxybutyl)nitrosamine (BBN) were studied. Male Fischer 344 rats, 6 weeks old,
      were given 0.05% BBN in the drinking water for 8 weeks followed by administration
      of piroxicam (0.0075% in the diet), lycopene (0.0025% in the drinking water)
      and/or beta-carotene (0.0025% in the drinking water) for 12 weeks, then killed
      for histological analysis of urinary bladder lesions. Cell proliferation
      potential was analyzed by immunohistochemical staining of the proliferative cell
      nuclear antigen (PCNA). Piroxicam alone, piroxicam+lycopene, and piroxicam
      +lycopene+ beta-carotene all significantly decreased the incidences and numbers
      of transitional cell carcinomas (TCCs), but the combination of piroxicam with
      carotenoids did not result in a clear improvement in the preventive potential of
      piroxicam. Piroxicam+ beta-carotene also caused a significant reduction and
      lycopene alone a slight but not significant reduction in the number of TCCs. In
      contrast, beta-carotene alone and lycopene+ beta-carotene were without inhibitory
      influence on any of the lesion categories examined, and the latter significantly
      increased the proportion of high-grade TCCs. Nevertheless, all of the
      chemopreventive agents, either alone or in combination, significantly decreased
      the TCC PCNA index, the effect extending to the surrounding epithelium in the
      piroxicam+lycopene and piroxicam+lycopene+beta-carotene groups. These results
      indicate that the NSAID piroxicam may be a more effective chemopreventive agent
      than lycopene and beta-carotene for superficial urinary bladder carcinogenesis.

PMID- 9263532
TI  - Inhibitory activity of green and black tea in a free radical-generating system
      using 2-amino-3-methylimidazo[4,5-f]quinoline as substrate.
AB  - Green tea and black tea inhibit colon carcinogenesis in rats exposed to the
      cooked meat mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). In the present
      investigation, green tea, black tea and (-)-epigallocatechin gallate (EGCG) were
      shown to block the production of oxygen free radicals derived from IQ in the
      presence of NADPH-cytochrome P450 reductase. In kinetic studies using IQ as the
      substrate and DMPO as a free radical spin trap, EGCG increased the K(m) of the
      reaction without altering Vmax, suggesting competitive enzyme inhibition (Ki =
      9.96 microM). This was confirmed in spectrophotometric studies using cytochrome c
      as the substrate, in which EGCG acted as a competitive inhibitor of NADPH
      cytochrome P450 reductase (Ki = 9.7 microM). These results suggest that the
      inhibitory activities of green tea and black tea in electron spin resonance
      assays using IQ as the substrate for the reductase are related to an indirect
      effect on the enzyme rather than via direct scavenging of the free radicals. The
      possible implications of these findings are discussed in the context of pathways
      involved in the activation and detoxification of IQ in the colon.

PMID- 9263533
TI  - Microsatellite instability in lung cancer patients 40 years of age or younger.
AB  - Lung cancer in the young, which has the characteristics of a higher incidence of
      adenocarcinoma, lower male-to-female ratio of the patients, and less frequent
      smoking history in the patients, may possibly be associated with genetic
      predisposition to cancers. We studied six microsatellite loci (D2S123, D3S659,
      D3S966, D5S346, WT1, and TP53) in 18 surgically treated lung cancer patients aged
      25-40 years and nine control patients aged 62-74 to determine the presence of
      microsatellite instability (MSI) and to correlate its occurrence with
      clinicopathological characteristics. Of the 18 patients, 11 were female and seven
      were non-smokers. There were 15 adenocarcinomas and three squamous cell
      carcinomas, 15 (83%) of which had vascular invasion. MSI was positive in seven
      (39%) of 18 young patients and one (11%) of nine control patients. Moreover, MSIs
      in a half or more of six loci examined were demonstrated in five (28%) young
      patients, whereas no control patients showed such a high frequency of MSI. We
      observed no significant differences in clinical or pathologic parameters between
      cases with and without MSI. This result suggests that genetic factors play an
      important role in the development of lung cancer in young adults.

PMID- 9263534
TI  - Modulation of motility and proliferation of glioma cells by hepatocyte growth
      factor.
AB  - Invasive proliferation is a critical biological characteristic of gliomas. We
      evaluated the activities of hepatocyte growth factor (HGF) on proliferation and
      motility of glioma cells, comparing them with the effects of other growth factors
      (EGF, bFGF, PDGF-BB, TGF-beta 1). Seven primary culture lines all expressed c-met
      and HGF mRNA, and secreted HGF. HGF stimulated 3H-thymidine uptake of every
      glioma cell line (30 to 70% upregulation). Boyden chamber assay and scattering
      assay revealed that HGF promoted cell motility with chemokinetic and strong
      chemotactic activities. Concentric circle assay showed that HGF promoted two
      dimensional expansion (proliferation and motility) most strongly among the growth
      factors studied. Further, we analyzed 23 paraffin-embedded sections of surgically
      resected gliomas (7 grade II, 8 grade III, and 8 grade IV) by
      immunohistochemistry. Expression of HGF and Met increased with malignant
      progression of gliomas, suggesting that gliomas stimulated their invasive
      proliferation by autocrine HGF production. Neurons and vasculature were HGF
      positive, and Met-positive glioma cells gathered around them. The data indicate
      that neurons and vasculature, which are the main tracks of glioma invasion,
      augment chemotactic invasion and proliferation of gliomas by paracrine HGF
      secretion. Clearly HGF plays a critical role in invasive proliferation of glioma
      cells and it is therefore a candidate target of therapeutic intervention.

PMID- 9263535
TI  - In vivo effect of recombinant human leukemia inhibitory factor in primates.
AB  - Leukemia inhibitory factor (LIF) is known to be a causative factor for cachexia
      and thrombocytosis in nude mice bearing human cancer cells. In the present study,
      we investigated whether recombinant human (rh) LIF can induce these biological
      activities in a primate model. rhLIF was synthesized by the expression of LIF
      protein in Escherichia coli. rhLIF (5, 20, or 80 micrograms/kg) was administered
      subcutaneously twice daily to cynomolgus monkeys for 14 consecutive days. A
      remarkable decrease of body weight (10%) was observed in the 80 micrograms/kg/day
      group. Approximately two-fold increases in platelet counts were observed at doses
      higher than 5 micrograms/kg/day when compared with control counts. These
      biological effects disappeared soon after the cessation of rhLIF treatment.
      Macroscopically, a remarkable reduction in subcutaneous fatty tissues and severe
      splenomegaly were observed. The results of this study demonstrate that rhLIF
      induces weight loss and thrombocytosis in a primate model.

PMID- 9263536
TI  - Protective effect of recombinant human leukemia inhibitory factor against
      thrombocytopenia in carboplatin-treated mice.
AB  - The protective effect of recombinant human leukemia inhibitory factor (rhLIF)
      against development of thrombocytopenia in carboplatin (CBDCA; cis-diammine-1,1
      cyclobutane dicarboxylate platinum II)-treated mice was examined. The optimal
      dose of rhLIF was determined by administering doses of rhLIF ranging from 0.2 to
      20 micrograms/day intraperitoneally to normal BALB/c mice, and by analyzing
      platelet counts. Platelet counts significantly increased at doses over 0.2
      microgram/day. When 20 micrograms/day rhLIF was injected for 7 days, platelet
      counts increased to 240% of control. A remarkable weight loss occurred in the 20
      micrograms/day group, but no weight loss was detected at doses of less than 10
      micrograms/day. The rhLIF dose of 4 micrograms/day was therefore used to examine
      the protective effect against carboplatin-induced thrombocytopenia in mice. The
      intravenous injection of 100 mg/kg carboplatin caused a significant
      thrombocytopenia with a nadir on day 8. The administration of 4 micrograms/day
      rhLIF intraperitoneally for 7 days promoted the recovery of platelet counts from
      day 5 after the injection of carboplatin. These results suggest that rhLIF at a
      suboptimal dose might be a useful therapeutic agent for chemotherapy-induced
      thrombocytopenia.

PMID- 9263537
TI  - Fibrotic focus in invasive ductal carcinoma of the breast: a histopathological
      prognostic parameter for tumor recurrence and tumor death within three years
      after the initial operation.
AB  - We investigated whether the presence of a fibrotic focus (FF) in the primary
      lesion and in lymph node metastasis is a good predictor of early tumor recurrence
      or death in patients with invasive ductal carcinoma (IDC). Multivariate relative
      risk (RR) of tumor recurrence and death according to the presence of FF in the
      primary tumor was estimated using the Cox proportional hazards regression model
      with adjustment for other prognostic factors (histologic grade, T classification,
      nodal status, tumor necrosis, DNA ploidy, c-erbB-2 protein expression, p53
      protein expression, and labeling index of proliferating cell nuclear antigen).
      For the evaluation of the metastatic status in the axillary lymph nodes, RR of
      multivariate analysis was adjusted for the presence of FF in the metastatic tumor
      and the number of lymph nodes involved (1-3 and > 3). The presence of FF
      increased the RR of tumor recurrence significantly for the cases in all stages,
      and especially for those in stages I and II (RR = 6.9, P < 0.05 and RR = 25.0, P
      < 0.005, respectively). All cases that died of disease had FF. Among IDCs with
      FF, 24 cases had FF in lymph node metastasis. Significantly higher RRs of tumor
      recurrence and death were observed in cases with FF in lymph node metastasis than
      in those without it (RR = 2.0, P < 0.001 and RR = 5.9, P < 0.05, respectively).
      It was suggested that the presence of FF is an important predictor of early tumor
      recurrence or death in patients with IDCs. The presence of FF in lymph node
      metastatic lesions is also a significant prognostic parameter.

PMID- 9263538
TI  - Apoptosis induced by NS-398, a selective cyclooxygenase-2 inhibitor, in human
      colorectal cancer cell lines.
AB  - Recent studies have suggested that apoptosis is a key phenomenon in the
      chemopreventive action of nonsteroidal antiinflammatory drugs (NSAIDs), which
      exhibit cancer-preventive and tumor-regressive effects in the human colon. The
      effect of NS-398, N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide, which is a
      selective inhibitor of cyclooxygenase-2 (COX-2), on the induction of apoptosis in
      two human colorectal cancer cell lines (Colo320 and THRC) was determined. The
      apoptotic ratios (-fold vs. control value) of Colo320 in the presence of 100
      microM indomethacin and NS-398 were 3.3 +/- 1.5 and 9.0 +/- 0.94, and those of
      THRC were 2.3 +/- 0.46 and 7.4 +/- 0.87, respectively. The ability of NS-398 to
      induce apoptosis is greater than that of indomethacin. Both indomethacin and NS
      398 reduced the cell proliferation in a concentration-dependent manner. The IC50
      values of NS-398 (54.8 +/- 3.6 and 77.2 +/- 4.9 microM) were significantly lower
      than those of indomethacin (206.3 +/- 43.0 and 180.3 +/- 22.6 microM) at P < 0.01
      in Colo320 and THRC cell lines, respectively. These findings suggest that NS-398,
      a selective inhibitor of COX-2, is a possible candidate for a chemopreventive
      agent with a potent apoptosis-inducing effect and low ulcerogenic activity.

PMID- 9263540
TI  - Viscoelastic properties of the superficial musculoaponeurotic system (SMAS): a
      microscopic and mechanical study.
AB  - A study was undertaken to determine the physical properties and microscopic
      structure of the superficial musculoaponeurotic system (SMAS) tissue. Forty
      virginal specimens and eight reoperated specimens were examined. The following
      findings were discovered. 1) Microscopic appearance shows the SMAS to consist of
      collagen fibers, a relatively high concentration of elastic fibers interspersed
      with fat cells. 2) On scanning electron microscopy, the virginal SMAS shows the
      collagen fibers to have a similar convoluted appearance as in the dermis. There
      is some evidence of parallelization of the collagen fibers in the reexcised SMAS
      specimens. 3) Mechanical testing (Instron) demonstrates that both the SMAS and
      preauricular skin were subjected to a series of loading/ unloading tests at
      various rates, amplitudes, and stress relaxation tests. Both sets of specimens
      indicated definite viscoelastic properties. Although the mechanical behavior of
      both tissues was somewhat similar, the viscoelastic effect of the SMAS was less
      pronounced. A slackening effect of the SMAS indicated a gradual expansion of the
      SMAS postoperatively. These results could provide some indication of the long
      term effects of SMAS surgery.

PMID- 9263541
TI  - CAST liposuction of the arm improves aesthetic results.
AB  - Lipocontouring the arm has a lower degree of patient satisfaction compared to
      other regions since untoward sequelae such as sagging and wrinkled skin may
      result. Circumferential para-Axillary Superficial Tumescent (CAST) liposuction
      was offered as an alternative to traditional arm liposuction or brachioplasty to
      59 patients. Fifty-three of 59 patients (89.9%) were satisfied or very satisfied
      with the procedure; six patients (10.2%) requested secondary procedures; four,
      further liposuction (6.8%); two, brachioplasty (3.4%). Although temporary
      untoward sequelae (15.3%) and minor complications (8.5%) were not infrequent and
      more vigorous postoperative care necessary, the final aesthetic result was rarely
      compromised and patient satisfaction was high.

PMID- 9263539
TI  - Imaging of recurrent intestinal carcinoma with indium-111-labeled anti
      carcinoembryonic antigen monoclonal antibody CEA102.
AB  - CEA102 is a mouse immunoglobulin G1 monoclonal antibody (mAb) that detects an
      epitope of carcinoembryonic antigen (CEA). The biodistribution and imaging
      characteristics of indium-111-labeled (111-In)-mAb CEA102 were studied in 1
      primary and 9 extrahepatic recurrent intestinal carcinoma patients. Evaluation
      included antibody pharmacokinetics and assessment of antibody distribution in
      surgical specimens, in comparison with whole body imaging using a gamma camera,
      and imaging with single photon emission computed tomography. Selective mAb CEA102
      localization to tumor tissue was demonstrated in 7 patients with tumors over 2 cm
      in size, and the external images correlated well with the results of surgical
      inspection, pathological examination, and tissue radioactivity measurements.
      Tumor:serum ratios ranged from 0.20:1 to 3.22:1, and serial biodistribution study
      of "regions of interest" also demonstrated a high radioactivity in the tumor.
      These results indicated the potential exploitability of the 111-In-labeled mAb
      CEA102 in radioimmunodetection of primary and extrahepatic recurrence of CEA
      positive intestinal carcinomas.

PMID- 9263542
TI  - Cutaneous hyperpigmentation caused by liposuction.
AB  - A wide range of sequels have been described as derived from a bad technique or a
      bad indication of liposuction. We present the cases of three patients who
      underwent a syringe liposuction of hips and lower limbs and had cutaneous
      hyperpigmentation as a sequel in the treated zone. We review the ethiopatogenic
      circumstances and their evolution.

PMID- 9263543
TI  - Extracorporeal septoplasty combined with open rhinoplasty.
AB  - Extracorporeal septoplasty is a radical solution for the severely deviated nose.
      The major problems associated with this procedure are fixation of the septal
      cartilage graft and dorsal irregularities. Extracorporeal septoplasty was
      performed in combination with open rhinoplasty in 17 patients with severe nasal
      deformities. In this technique septum was totally removed through the columellar
      incision of open rhinoplasty, corrected outside, and replaced as a free "L"
      shaped cartilage graft. The cartilage graft was fixated to the upper lateral
      cartilages to restore the natural relations of the anatomical structures.
      Additional rhinoplastic manipulations were also performed. The follow-up period
      was up to 18 months. The overall result was successful in all patients. Nasal
      deviation did not recur and secondary revisions were not needed for any patient
      during follow-up.

PMID- 9263544
TI  - New surgical concepts: nasal tip function.
AB  - Since the birth of plastic surgery, rhinoplasty has been an outstanding chapter.
      Facial balance has been endeavoured with two parameters: size and shape. Now,
      however, the criterion for harmony has involved two more parameters; position and
      function. Position is related to other facial elements, such as, upper maxilla,
      upper lip, forehead, and frontonasal sulcus. Function is important because nasal
      superficial musculoaponeurotic system (SMAS) muscles are important for Nasal tip
      movement. To understand this better, we must analyze the nasal SMAS, which
      consists of primary or intrinsic and secondary or extrinsic muscles. When the
      extrinsics contract, they allow function of the intrinsics. They are the ala
      nasalis dilator, the ala nasalis elevator, the tranversus, and the tip depressor.
      Obvious hypertrophies of the dilator and the elevator has been observed in young
      athletes. Our method combines conventional, new, and modern aspects. It is
      conventional because the alar cartilages have been completely freed by
      intercartilaginous and marginal approaches, and the upper or lower border trimmed
      according to the case. It is more important to measure how much cartilage is
      left, than how much is removed. The new aspect is consideration of nasal SMAS to
      treat short noses that display a tendency to descend with laughter, and the
      modern aspect is the evaluation of dynamic surgical results, apart from the
      static.

PMID- 9263545
TI  - Technique for harvesting of conchal cartilage grafts.
AB  - Conchal cartilage is an important source of cartilage for the rhinoplasty surgeon
      [Falces E, Gorney M: Plast Reconstr Surg 50:147, 1972; Hage J: Brit J Plast Surg
      18:92, 1965; Juri J et al: Plast Reconstr Surg 63:377, 1979]. We describe a
      technique to harvest conchal cartilage which minimizes morbidity for the patient
      and produces an excellent scar.

PMID- 9263547
TI  - Double eyelid procedure by removal of transconjunctival orbital fat and buried
      sutures combined with sling technique to avoid wounding the eyelid.
AB  - In the typical transconjunctival buried suture procedure for double eyelids, the
      adhesion between the skin and the pretarsal tissue or conjunctiva through the
      tarsal plate and the sling with the skin, the levator, and Muller's muscle are
      obtained by suturing. These are assisted by the stab wound or a needle through
      the eyelid skin, and the skin wound takes several days to heal. Also these
      suturing knots are buried under the skin on the tarsal plate, so that these will
      tend to appear on the skin surface later on. Removing the excess orbital fat that
      migrates to the area of fixation and jeopardizes the effect of the suturing
      technique is performed with skin incision and usually leaves a linear scar. The
      author devised a method that makes a double eyelid with two linear, wide sutures
      that lie between the levator and Muller's muscle and the immediately adjacent
      subdermal tissue of the skin by using one thread. It also reduces the excess
      orbital fat through the conjunctiva without wounding the skin and makes face
      washing or application of make-up possible immediately after the operation. Only
      one ligation is left at the lateral subconjunctiva to avoid its appearance on the
      skin surface to effect easy correction in case necessary. This method has evolved
      from previous method of transcutaneously burying sutures for the double eyelid,
      which was made wide by a linear suture by using one thread. Insufficient results
      were observed in eight of 280 cases.

PMID- 9263546
TI  - Deep planed torso-abdominoplasty combined with buttocks pexy.
AB  - This new procedure was created for aesthetic purposes with the intention of
      creating a longer and more slender waist and at the same time treating
      neighboring areas. This procedure also is used to raise or change the position of
      a previous abdominoplasty scar. In addition it is also beneficial for treating
      gestation sequelae of the torso-abdominal wall, ptosis of the abdomen, vertical
      and horizontal enlargements of the musculoaponeurotic system, lipodystrophy,
      stretch marks, rhytidosis of the inguinal region, and ptosis of the external
      quadrant of the gluteous and the external trochanter area in one surgical
      procedure. It is not always necessary to apply the entire procedure to each case.
      The deep planed torso-abdominoplasty offers a broader selection of techniques for
      creating aesthetic contouring of the torso-abdominal wall, flanks, inguinal
      region, and outer thighs. It also creates pexy of the external quadrant of the
      gluteous region.

PMID- 9263548
TI  - Unusual palpebral foreign bodies.
AB  - We encountered cases of palpebral foreign bodies, which were a bamboo chip that
      entered in a trauma, a gelatinoid material that formed an iatrogenic ulcer, and
      self-injected lipstick. Treatments and complications of these unusual palpebral
      foreign bodies are evaluated.

PMID- 9263549
TI  - An outer-table suspension technique for endoscopic browlift.
AB  - For the past 2 years, we have sought to develop a stable and reliable technique
      for soft-tissue suspension in the endoscopic browlift, while eliminating the need
      for permanent or temporary anchoring screws. To this end, we have developed an
      outer calvarial table fixation technique. This technique allows direct fixation
      of the periosteum or galea to the outer table of the frontal bone through the use
      of an outer table calvarial tunnel. The technique has been used in 34 patients,
      21 of which were followed for more than a year. The results have been consistent
      and reliable. We feel this technique affords precise control of soft tissue
      suspension during endoscopic browlift, providing long-lasting elevation and
      lateral advancement of the brow complex.

PMID- 9263550
TI  - Differences in horizontal, neoclassical facial canons in Chinese (Han) and North
      American Caucasian populations.
AB  - To better our ability to analyze the facial disproportions of patients of Chinese
      ancestry, we compared the validity of four neoclassical canons of facial
      proportion in Chinese and North American Caucasians populations. We tested the
      frequency of four horizontal facial canons and their eight variations in 206
      healthy adults (105 males and 101 females, 18-25 years old) belonging to the
      predominant ethnic group (Han: 400 million) of the Chinese population, and
      compared them to those of 103 healthy young North American Caucasian adults. The
      nose width corresponded to one-quarter of the face width (the nasofacial canon)
      significantly more frequently in Chinese participants (51.5%) than in Caucasian
      adults (36.9%). The nose was narrower than one-quarter of the face width in 38.8%
      of North American Caucasians and in 21.8% of Chinese; this difference was also
      statistically significant. In defiance of the naso-oral canon, the mouths of
      Chinese people were significantly more often narrower than 1.5 times the nose
      width (71.8%), while in North American Caucasian ethnics the mouth was
      significantly more frequently wider (60.2%).

PMID- 9263551
TI  - Axillary reduction mammaplasty--Yhelda Felicio's technique.
AB  - The problem most common to the majority of mammary reductions is patient
      dissatisfaction due to breast scarring of lateralization of the breast. Many of
      these complications can be avoided by use of an axillary approach for correction
      of breast ptosis via the axillary skin incisions.

PMID- 9263552
TI  - Immediate reaugmentation of the breasts using bilaterally divided TRAM flaps
      after removing injected silicone gel and granulomas.
AB  - The authors present eight cases of reconstruction of the breasts using
      bilaterally divided TRAM flaps after removing the injected silicone gel and
      granulomas. In Japan, we have the opportunity to examine many patients who have
      had foreign substance injections to the breasts for purposes of augmentation
      however, most of them are now suffering from delayed complications. Until now we
      have reconstructed breasts such cases by use of silicone bag prostheses after
      removal of granulomas; however, now it is difficult to obtain silicone
      prostheses. Thus, we have decided to reconstruct by the use of autogenous
      cutaneous and adipose tissue flaps as presented by us in this article.

PMID- 9263553
TI  - The mini rhytidectomy.
AB  - A technique is described in which superficial musculoaponeurotic system (SMAS) is
      plicated from the deep temporal fascia above the zygoma to the level of the
      earlobe. This procedure requires only an extended preauricular incision. The neck
      is dealt with by liposuction. This technique is ideally suited to the younger
      patient requesting facelift and is based on a sound understanding of the anatomy
      of SMAS. The outcome of 35 patients who underwent this procedure during a 3.5
      year period are described. There were no cases of facial nerve paresis or hair
      loss. There were no cases of skin necrosis but two patients developed small
      hematomas and one patient complained of a stretched preauricular scar. The mini
      facelift leads to a satisfactory result in the younger patient requesting
      rhytidectomy. The technique is simple and safe and can easily be performed on an
      ambulatory basis. Complications are uncommon and of a minor nature.

PMID- 9263554
TI  - Should diastasis recti be corrected?
AB  - The plication of the anterior rectus sheath is a procedure that is performed by
      most surgeons during abdominoplasty. A main concern is whether the correction of
      recti diastasis is really effective and if it is stable. In order to verify the
      position of the rectus muscle, a CT-scan was used in 14 patients who underwent
      abdominoplasty with rectus plication to compare the preoperative situation of
      these muscles with their position 3 weeks and 6 months postoperatively. None of
      these patients had had previous abdominal surgery. The recti diastasis was
      corrected with a two-layer 2-0 Nylon suture. A dynamometer was used to measure
      the resistance force of the anterior aponeurosis of the rectus. In all cases the
      CT data shows that correction of the diastasis was achieved completely after 6
      months.

PMID- 9263555
TI  - Renal tolerance with the use of intralipid-amphotericin B in low-birth-weight
      neonates.
AB  - Amphotericin B is still the first-line therapy for neonatal fungal infections.
      With several comparative trials of intralipid-based amphotericin B (IL-AmB)
      demonstrating its clinical effectiveness and reduced renal toxicity in adults, we
      examined the renal tolerance and infection outcome in low-birth-weight infants in
      our 48-bed NICU treated with IL-AmB. Over 2 years, 52 patients (58 courses)
      received > or = 10 days of IL-AmB. Nineteen charts (23 episodes) were randomly
      accessed and reviewed. Mean birthweight = 747 grams, gestational age = 25.6
      weeks, total IL-AmB dosage = 19.8 +/- 3.3 mg/kg (n = 23); 20 of these episodes
      were fungal culture positive (9 fungemias). Only one patient (who died during
      therapy) had a rise in creatinine of > 0.3 mg/dL. Overall, serum creatinine
      decreased significantly after Day 10 of IL-AmB therapy, from 0.93 +/- 0.42 mg/dL
      at baseline, to 0.54 +/- 0.24 after 19 days of therapy (p < 0.0001). Serial urine
      output, serum potassium and potassium supplementation data showed no significant
      differences from baseline. No interruption of therapy nor infusion reactions
      occurred. Only one death occurred attributable to fungal infection. Intralipid
      amphotericin B may provide an effective alternative in the antifungal therapy of
      low birthweight neonates, without nephrotoxicity. Further prospective,
      comparative trials are warranted.

PMID- 9263556
TI  - Pneumothorax in pregnancy associated with cocaine use.
AB  - Pneumothorax is extremely rare during pregnancy. We describe two antepartum cases
      temporally associated with cocaine use with a review of the literature and
      discussion on treatment options. Case 1, a 39-year-old female, presented at 31.3
      weeks' gestation with a right pneumothorax after smoking crack cocaine. The
      pneumothorax was refractory to conservative therapy necessitating transaxillary
      resection of apical lung blebs. Fetal compromise was diagnosed at 34.6 weeks of
      gestation requiring induction of labor and subsequent delivery of a viable
      infant. Case 2, a 27-year-old female, presented at 28.9 weeks of pregnancy with
      her third episode of recurrent left pneumothorax. Thoracotomy and excision of
      lung bleb was performed and the patient was discharged on postoperative Day 5.
      Although the patient denied any history of drug use, drug screens were positive
      for cocaine. The patient delivered at term without further complications. Cocaine
      use is a predisposing factor for pneumothorax during pregnancy. Spontaneous
      pneumothorax carries a high risk of recurrence, possibly higher if induced by
      continued cocaine-use. Surgical intervention should be considered in refractory
      or recurrent cases.

PMID- 9263557
TI  - In utero management of hydrops fetalis caused by critical aortic stenosis.
AB  - Hydrops fetalis is rarely associated with congestive heart failure caused by
      obstructive left-sided heart lesions. There are rare cases of live born neonates
      with critical congenital valvar aortic stenosis and hydrops reported in the
      literature, all with fatal outcomes. This report describes, to the best of our
      knowledge, the first two newborns who were diagnosed prenatally to have hydrops
      fetalis caused by critical valvar aortic stenosis, who were treated prenatally
      with digoxin and who postnatally had successful percutaneous balloon aortic
      valvuloplasty. Both patients had not only left but right ventricular dysfunction.
      We speculate that right ventricular dysfunction was a contributing factor in the
      development of hydrops in these patients and in utero medical therapy with
      digoxin is associated with resolution of the hydrops before delivery.

PMID- 9263558
TI  - Evolution of fetal ventricular aneurysms and diverticula of the heart: an
      echocardiographic study.
AB  - Due to the rarity of congenital ventricular diverticula and aneurysms, their
      natural history remains unclear. An excellent prognosis has been suggested for
      those cases diagnosed during fetal life: From October 1992 to January 1996 seven
      fetuses were diagnosed with ventricular diverticula or aneurysms. Gestational age
      ranged from 18 to 36 weeks. The indications for fetal echocardiogram were
      cardiomegaly, abnormal four-chamber view, a large pericardial effusion, and
      hydrothorax. Echocardiography revealed a moderate sized apical left ventricular
      aneurysm (2), a small subvalvular right ventricular diverticulum (1), small
      apical right ventricular diverticulum (2), a large submitral left ventricular
      aneurysm (1), and a large diverticulum arising from the lateral free wall of the
      left ventricle (1). Decreased left ventricular function was detected in three
      fetuses with left ventricular aneurysms. Two fetuses with large lesions,
      developed hydrops and died in utero. Postnatal echocardiograms confirmed prenatal
      findings in all survivors. All infants remained asymptomatic, with age on follow
      up from 8 to 24 months. An accurate diagnosis of ventricular diverticula and
      aneurysms is feasible prenatally. Outcome depends on the size and progression of
      the lesion. The presence of a large pericardial effusion in three cases with a
      diverticula was noted.

PMID- 9263559
TI  - Serum tumor necrosis factor-alpha in neonatal sepsis.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is thought to be an important mediator in
      the pathogenesis of neonatal septicemia. To assess the role of TNF-alpha in
      neonatal sepsis, serum levels of TNF-alpha were measured in a group of neonates
      with septicemia and compared with the levels of gestational-postnatal, age
      matched healthy controls. The relationships between severity of infection, the
      nature of causative microorganisms, and TNF-alpha levels were also investigated
      in this prospective study. A total of 49 infants (25 full-term, 24 preterm) with
      proven sepsis and 40 healthy infants (20 full-term, 20 preterm) were included.
      Serum TNF-alpha levels were measured using the TNF-alpha immunoradiometric assay.
      The median level of TNF-alpha was found to be significantly higher in infants
      suffering from sepsis (154 pg/mL) particularly in those with septic shock (242.5
      pg/mL) as compared to healthy controls (61.5 pg/mL) (p < 0.001). No correlation
      was found between TNF-alpha and postnatal ages, gestational ages or birth weights
      of the infants. TNF-alpha levels were not different in surviving and terminal
      neonates. Although serum, TNF-alpha levels were found to be slightly higher in
      gram-negative septicemia, the difference was not significant. These findings
      suggest that TNF-alpha plays an important role in the pathophysiology of neonatal
      septicemia, but its importance as a prognostic factor is not yet clear.

PMID- 9263560
TI  - Tocolytic treatment for preterm contractions with and without cervical changes.
AB  - Our purpose was to evaluate the impact of intravenous and oral tocolysis on
      prolongation of gestation for women with preterm uterine contractions and/or
      labor. Candidates for evaluation and treatment including women with contractions
      between 24 and 35 weeks. Two hundred women (group I) without cervical changes met
      the protocol criteria and 175 women (group II) who presented with or developed
      cervical changes were treated by protocol. A representative sample of both groups
      received oral terbutaline maintenance therapy until 37 weeks' gestation. Primary
      outcome variables included the length of gestation obtained following initial
      treatment and the preterm birth rate. Women in group II were twice as likely to
      deliver before 35 weeks, 23% versus 9.5%, respectively, and to have a delivery
      before 37 weeks' gestation, 45% versus 22%, respectively, (p < 0.05). There was
      no significant difference in days gained in utero for women on oral terbutaline
      for either group. Women in group II on oral therapy were more likely to be
      readmitted and retreated with parenteral tocolysis. In conclusion, oral
      maintenance tocolysis has no significant impact on further prolongation of
      pregnancy after intravenous tocolysis.

PMID- 9263561
TI  - Perinatal outcome of pregnancies complicated with varicella infection during the
      first 20 weeks of gestation.
AB  - Varicella-Zoster (V-Z) virus infection during pregnancy is uncommon.
      Nevertheless, it has importance due to the risk of vertical transmission of the
      infection and also because of a higher morbidity rate among pregnant women. The
      cases of varicella infection that occur in the first and second trimesters of
      pregnancy are occasionally associated to the development of congenital varicella
      syndrome. We studied 22 women whose pregnancy was complicated with varicella
      during the first 20 weeks of gestation. The average age of these patients was 20
      +/- 3.6 years with a range of 16 to 20 years. None of the patients presented
      complications due to the V-Z virus infection. Two pregnancies finalized in
      preterm labor. None of the newborns had congenital anormalies; one presented
      microcephaly, and another low birth weight. There was no significant difference
      between the infants of women with varicella and those of the controls in birth
      weight, size, and head circumference. We concluded that varicella infection
      during the first 20 weeks of gestation was not associated with serious maternal
      morbidity, and has low repercussion in the pregnancy outcome and the fetus.

PMID- 9263562
TI  - Neonatal thrombocytopenia: incidence, serological and clinical observations.
AB  - In this study, platelet counts were determined from the cord blood of consecutive
      9142 newborns. Neonates with known autoimmune thrombocytopenia were not included.
      The platelet count < 100 x 10(9)/L was found in 64 newborns. In five of them,
      neonatal alloimmune thrombocytopenia (NAIT) was diagnosed. The overall incidence
      of neonatal thrombocytopenia was 0.7%, the incidence of NAIT was about 10 times
      less. Serological and clinical observations are summarized from 238
      thrombocytopenic newborns (54 from the above group and 184 previously referred to
      serological investigations). All of the newborns were divided into two groups:
      NAIT (46 cases) and other thrombocytopenias (192 cases). Among platelet-specific
      antibodies in NAIT, 91.4% were anti-HPA-1a, the rest were anti-HPA-1b and anti
      HPA-5b. In the majority of the cases, antibodies were detectable by the platelet
      suspension immunofluorescence test (PSIFT) and monoclonal antibody immobilization
      of platelet antigens (MAIPA) assay. In 19.6% cases, antibodies were detectable by
      MAIPA only. In 10.9% of these cases, antibodies were undetectable.
      Thrombocytopenia < 50 x 10(9)/L and hemorrhagic diathesis were more often
      observed in NAIT than in other thrombocytopenias, whereas associated disorders
      that could contribute to thrombocytopenia, here observed almost only in the
      latter group. We also report certain other observations, such as the presence of
      anti-HLA antibodies, a rise in the anti-HPA-1 a antibody titer after infection
      without pregnancy, and a higher incidence of petechiae in nonimmune
      thrombocytopenia as compared with the incidence of low platelet counts.

PMID- 9263563
TI  - Fetal but not maternal serum cytokine levels correlate with histologic acute
      placental inflammation.
AB  - Our objective was to determine if placental histologic acute inflammation is
      related to maternal and fetal serum cytokine levels in preterm labor, using a
      data set previously constructed blinded to histopathologic information. To this
      goal in 1992, 32 consecutive patients at 20-36 weeks with progressive labor and
      tocolytic failure were recruited. Maternal serum sampled during the active phase
      of labor, and fetal (umbilical vein) serum were assayed by ELISA for levels of
      soluble interleukin-1 beta (IL-1 beta), soluble interleukin-2 receptor (IL-2 R),
      and interleukin 6 (IL-6) (T-Cell Diagnostics). Acute placental inflammation was
      scored by two groups blinded to clinical data, and the average scores analyzed
      for relationships to serum cytokine levels. Weighted kappa values, reflecting
      interobserver agreement in scoring of acute inflammation, were: amnion 0.84;
      choriodecidua 0.84; umbilical cord 0.85; and chorionic plate 0.73. Fetal levels
      of IL-1 beta and IL-2 R were higher with grade 3-4 acute amnionitis than with
      grades 0-2 (p = 0.022 and p = 0.023). Fetal levels of all three cytokines were
      higher in grade 3-4 umbilical vasculitis (IL-1 beta p = 0.008, IL-2 R p = 0.01,
      and IL-6 p = 0.03). In contrast, maternal serum cytokine levels were not
      associated with presence or severity of histologic evidence of acute placental
      inflammation. Histologic acute inflammation was not related to duration of labor,
      interval from membrane rupture to delivery, and presence or duration of
      antibiotic therapy. We conclude that fetal serum, but not maternal serum cytokine
      levels, are correlated with histologic evidence of acute placental inflammation,
      and may reflect a predominant placental origin of the cytokines.

PMID- 9263564
TI  - In utero progression of isolated renal pelvis dilation.
AB  - The objective of this study to determine the risk of in uteroprogression of renal
      pelvis dilation when detected on antenatal ultrasound examination. We reviewed
      230 fetuses with evidence of renal pelvis dilation. At least one exam was
      subsequently performed prior to delivery in all cases. Renal pelvis dilation was
      defined as an anterior-posterior renal pelvis measurement > 4 mm at < 32 weeks'
      and > 7 mm at > or = 32 weeks' gestation. Hydronephrosis was considered to be
      present when the renal pelvis measured +10 mm independent of gestational age.
      Multiple gestations and fetuses with additional congenital anomalies were
      excluded. The mean gestational age at diagnosis was 24 weeks. Renal pelvis
      dilation progressed to hydronephrosis in a total of 10.9% (25 of 230) of fetuses.
      There was a 3.3% chance of unilateral renal pelvis dilation progressing to
      hydronephrosis versus 26.0% in bilateral dilation (OR 10.4 [95% Cl 3.5-33.3]). Of
      those fetuses with progression, 80% had bilateral dilation (p < 0.0001). There
      was no difference in progression between right and left kidneys. Additionally,
      gender, gestational age at diagnosis and delivery, and birth weight did not
      differ between those fetuses with and without progression. The hydronephrosis in
      7 of 25 (28%) regressed to pyelectasis on a subsequent ultrasound exam. Thus, the
      overall rate of progression of renal pelvis dilation to persistent hydronephrosis
      was 7.8% (18 of 230). In conclusion, the risk of isolated renal pelvis dilation
      progressing to hydronephrosis is low. Although bilateral pelvis dilation carries
      a higher risk for progression, no fetus in our study required in utero
      intervention. A follow up scan prior to delivery may be considered to identify
      those fetuses who will require postpartum intervention.

PMID- 9263565
TI  - Ultrasound detection of Apert syndrome: a case report and literature review.
AB  - Apert Syndrome is characterized by craniosynostosis, bilateral syndactyly, and
      midfacial hypoplasia. Although it was first described by Wheaton in 1894, it was
      first diagnosed prenatally only a decade ago-with only five cases reported in the
      literature. A sixth case is reported here. Prenatal diagnosis of Apert syndrome
      is reviewed.

PMID- 9263566
TI  - Brain death during pregnancy: tocolytic therapy and aggressive maternal support
      on behalf of the fetus.
AB  - We report a case of maternal brain death at 25 weeks gestation in which
      aggressive maternal hemodynamic, respiratory, and metabolic support and tocolytic
      drug therapy resulted in prolongation of pregnancy for 25 days. The indication
      for delivery was torulopsis giabrata amnionitis, which may have occurred due to
      transmembrane or transplacental route. The baby was treated for fungal sepsis,
      and did well. Premature labor may occur spontaneously after maternal brain death,
      and may be precipitated by infection or by maternal drug therapy. The myriad of
      hemodynamic and endocrine issues associated with maternal brain death complicate
      the choice of tocolytic drugs, but this case illustrates that uterine activity
      can be successfully blocked, potentially diminishing risks to the newborn,
      following the tragedy of maternal brain death during pregnancy.

PMID- 9263567
TI  - Immunohistochemical localization in the stallion genital tract, and topography on
      spermatozoa of seminal plasma protein SSP-7, a member of the spermadhesin protein
      family.
AB  - SSP-7 is a protein originally isolated from stallion seminal plasma. It has
      extensive amino acid sequence homology with boar spermadhesin AWN, and, like its
      porcine counterpart, SSP-7 displays zona pellucida-binding activity. Strikingly,
      however, immunohistochemical studies presented here show that the stallion and
      the boar spermadhesin homologues are secreted at different places of the male
      genital tract. Furthermore, indirect immunofluorescence shows that the topography
      of SSP-7 on the surface of stallion spermatozoa is restricted to the equatorial
      segment, whereas boar AWN epitopes cover the entire acrosomal cap membrane. The
      different cellular origin and compartimentalization of spermadhesin molecules in
      different species suggest that structurally related proteins could be involved in
      species-specific aspects of mammalian fertilization.

PMID- 9263568
TI  - Granulocyte elastase indicates silent male genital tract inflammation and
      appropriate anti-inflammatory treatment.
AB  - Diagnosis of male genital inflammations plays a significant role in andrology.
      Although genital infections are often silent, they can severely impair male
      fertility. In the seminal plasma of 305 patients, immunoglobulins IgG, IgA,
      complement factor C3C, coeruloplasmin and the number of peroxidase-positive cells
      were determined in addition to conventional semen parameters and microbiological
      investigations. A leukocyte esterase dipstick test was also carried out. All
      these parameters were correlated with the granulocyte elastase determined by an
      enzyme immunoassay. A highly significant correlation between elastase
      concentrations and the other parameters indicating inflammation was observed.
      After anti-inflammatory treatment, elastase concentrations decreased markedly.
      The results showed that exact quantification of granulocyte elastase is a very
      specific and sensitive method to distinguish inflammatory from non-inflammatory
      male adnexal affections, which is appropriate for control of anti-inflammatory
      treatment and facilitates the diagnosis of inflammatory processes in andrology.

PMID- 9263569
TI  - CD 45/67 immunobead preparation of human semen activates granulocytes.
AB  - In human semen reactive oxygen species (ROS) produced by spermatozoa or
      leukocytes can impair spermatozoa functions. The objective of this study was to
      assess the effects of CD 45- and/or CD 67 immunobead preparation on the
      chemiluminescence (CL) of seminal plasma free ejaculate cells (= original cell
      suspension), as well as of the spermatozoa and leukocyte fractions. The original
      cell suspensions of 68 infertile and 8 fertile men were incubated with CD 45 or
      CD 67 immunobeads. After separation in a magnetic field the luminol
      chemiluminescence of the original cell suspensions, the spermatozoa and the
      leukocyte fractions were recorded on a luminometer. Spermatozoa fractions did not
      contain any leukocytes as no increase in CL-counts occurred after addition of
      FMLP. The number of peroxidase-positive cells (per 10(7) spermatozoa) correlated
      with the CL of the original cell suspensions (r = 0.7; P < 0.0001) as well as the
      CL of the spermatozoa and the leukocyte fractions after CD 45 or CD 67
      preparation (r = 0.64; P < 0.0001). The CL of the spermatozoa and of the
      leukocyte fractions after CD 45 immunobead incubation were significantly
      correlated (r = 0.091; P < 0.0001). According to these data contaminating
      leukocytes could be eliminated by immunobead preparation. However, incubation of
      original cell suspensions with CD 45 or CD 67 immunobeads stimulated leukocytes
      to release soluble products resulting in elevated CL signals both in the
      leukocyte and the spermatozoa fractions. These effects have to be taken into
      account when using immunobeads for the preparation of human semen.

PMID- 9263570
TI  - Chronic ethanol intake may delay the onset of gossypol-induced infertility in the
      male rat.
AB  - Parameters were obtained from the reproductive organs of ethanol-fed, gossypol
      treated Sprague Dawley rats. The experimental animals were fed either on a normal
      (15.17%) or low protein (8.00%) diet. Measurements included reproductive organ
      weights, seminal characteristics, serum concentration of testosterone and
      histological, stereological and histomorphometric evaluation of the testis. The
      testis size, length and diameter of the seminiferous tubule had the least values
      in the protein-malnourished, gossypol-treated rats (3.01 +/- 0.26 g, 0.56 +/-
      0.03 m, 281.34 +/- 11.30 microns), in comparison to corresponding animals which
      had received ethanol simultaneously with gossypol (3.40 +/- 0.25, 0.71 +/- 0.06
      m, 314.42 +/- 11.61 microns). As gossypol and ethanol are both associated with
      reduced reproductive capacity, this unexpected but interesting finding lends
      support to the hypothesis that either a normal dietary protein or ethanol
      consumption may modify the action of gossypol on body tissues, including the
      testis. This effect, presumably mediated through changes caused to the
      bioavailability of gossypol, modifies its antifertility activity. The present
      observation further highlights the need to consider the concurrent administration
      of other drugs, such as alcohol, and the nutritional status in the evaluation of
      gossypol for various potential uses.

PMID- 9263571
TI  - Assessment of hyperactivation, acrosome reaction and motility characteristics of
      spermatozoa from semen of men of proven fertility and unexplained infertility.
AB  - Semen from men of proven fertility was compared with that of men with unexplained
      infertility to determine differences in spermatozoal functions such as
      hyperactivation and acrosome reaction and spermatozoal motility characteristics.
      The hyperactivated spermatozoa in both groups could be visualised on the monitor
      of the Computer Assisted Semen Analyser and they exhibited 'circling',
      'thrashing', 'starspin' and 'helical' motility patterns and the mean
      hyperactivation rates were not significantly different. However, 20% of the men
      with unexplained infertility did not exhibit hyperactivation compared to only 4%
      in the fertile group. Furthermore, the semen from infertile men when evaluated
      for hyperactivation could be categorised into two groups with those having lower
      hyperactivation (< 10% or < 6% after 4 and 6 h of incubation respectively),
      forming the first group, and those having a higher hyperactivation rate
      constituting the second group. In the fertile men such distinct groups were not
      visible and the percentage hyperactivation ranged from 1 to 16%. No significant
      differences were observed in the rate of acrosome reaction of fertile and
      unexplained infertile men. The non-hyperactivated spermatozoa from unexplained
      infertile men showed a significant increase in path velocity (VAP), curvilinear
      velocity (VCL) and amplitude of lateral head displacement (ALH) and a decrease in
      linearity (LIN) and straightness (STR) compared to spermatozoa from fertile men.
      Furthermore, the hyperactivated spermatozoa from infertile men also showed an
      increase in progressive velocity (VSL) (only after 2 h of incubation) and LIN and
      decrease in ALH and beat cross frequency (BCF) compared to spermatozoa from
      fertile men. The results are discussed in the light of the importance of the
      above spermatozoal functions and spermatozoal parameters in fertilization.

PMID- 9263572
TI  - The correlation of Ureaplasma urealyticum infection with infertility.
AB  - A prevalence study of Ureaplasma urealyticum (UU) infection of the male genital
      tract was carried out in Shanghai between March 1992 and June 1995. Significantly
      higher frequency of UU infection was found among infertile males (549/1416) as
      compared to fertile controls (34/375). Examination of 8 specimens each from
      infertile men and fertile subjects by electron microscopy, immunogold and
      immunofluorescence techniques, demonstrated adhesion of Ureaplasma urealyticum to
      the membrane of spermatozoa and exfoliated germ cells. In addition, gold
      particles on Ureaplasma urealyticum were found to be adhered to the sperm surface
      in 4 of the 8 samples. Strong specific anti-UU fluorescence was detected in 6 of
      8 samples, mainly on the midpieces and post-acrosomal regions of the spermatozoa.
      To further study the effects of Ureaplasma urealyticum on fertility, 47 male
      Sprague-Dawley (SD) rats were infected artificially with Ureaplasma urealyticum
      serotype 8 (T960). Morphological changes in the seminiferous tubules were
      observed 3-5 weeks after inoculation in the sacrificed animals. Dramatic
      impairment of spermatogenesis of both testes was found in 11 rats. Mating
      experiment confirmed infertility in 12 of 40 rats. Offsprings of the infected
      rats were significantly smaller than those of controls in terms of prenatal
      weights and birthweights.

PMID- 9263573
TI  - Maintenance of human sperm motility and prevention of oxidative damage through co
      culture incubation.
AB  - Co-culture incubation is one of the important techniques used in basic and
      clinical research of assisted reproduction. In this study, sperm samples from 40
      healthy donors were prepared for co-culture incubation with Vero cells which had
      been derived from the kidney fibroblasts of the African green monkey,
      Cercopithecus aethiops. We found that the motility characteristics of ejaculated
      human sperm co-cultured with Vero cells were largely maintained and the
      percentage of hyperactivated sperm in the co-culture group was not affected.
      While the sperm of the control group completely lost the motility at 12 h
      incubation at 37 degrees C in 5% CO2, the sperm co-cultured with Vero cells still
      maintained 74% of the original motility. Lipid peroxidation and accumulation of 8
      hydroxy-2'-deoxyguanosine in spermatozoa were also reduced by the co-culture
      incubation, which strongly indicates that intercellular interactions may play
      some role in the maintenance of sperm functions. We conclude that the oxidative
      damage in vitro of the sperm can be reduced by the co-culture system and thereby
      maintains the function of sperm from oxidative damage.

PMID- 9263574
TI  - The effects of lactate and beta-hydroxybutyrate on the energy metabolism and
      neural activity of hippocampal slices from adult and immature rat.
AB  - We investigated the correlation between energy metabolism and neural activity
      during glucose deprivation and during replacement of glucose with lactate and
      beta-hydroxybutyrate (OHBA) in neural tissue from rats of different ages.
      Hippocampal slices were prepared from 4-, 7-, 10-, 13- and 16-day-old and adult
      rats. The population spikes (PS) were recorded in the pyramidal cell layer of the
      CA3 area as the index of neural activity. ATP and creatine-phosphate (CrP) levels
      in each slice were determined during glucose deprivation and during replacement
      of glucose with lactate or OHBA. After deprivation of glucose, the PS of the
      slices from 4-, 7- and 10-day-old and adult rats decayed and extinguished in 30
      min and the decay time was shortened according to the age of the rat. The levels
      of ATP and CrP in the slices also decreased, but to a lesser extent than the
      amplitudes of PS. After substitution of lactate or beta-hydroxybutyrate (OHBA)
      for glucose, PS of the adult rat disappeared as was the case with glucose
      deprivation, although the levels of high energy phosphates were well maintained.
      In the case of the immature rat, however, PS decayed more slowly. Especially in
      the case of 4-day-old rat, ATP and CrP in the slices were maintained as high as
      those under the initial concentrations and PS amplitude showed no decay even
      after 60 min. These results indicate that the presence of glucose is essential
      for neural activity in the adult rat, and lactate or OHBA cannot replace it for
      the maintenance of neural activity. In the immature rat, glucose metabolites such
      as lactate and OHBA are available for both neural activity as well as maintaining
      the levels of high-energy phosphates in the tissue slice.

PMID- 9263575
TI  - Apoptosis is induced by choline deficiency in fetal brain and in PC12 cells.
AB  - Treatment of rats with choline during critical periods in brain development
      results in long-lasting enhancement of spatial memory in their offspring.
      Apoptosis is a normal process during brain development, and, in some tissues, is
      modulated by the availability of the nutrient choline. In these studies, we
      examined whether availability of choline influences apoptosis in fetal brain and
      in the PC12 cell line derived from a rat pheochromocytoma. Timed-bred Sprague
      Dawley rats were fed a choline-deficient (CD), choline-control, or choline
      supplemented (CS) diet for 6 days and, on embryonic day 18, fetal brain slices
      were prepared and apoptosis was assessed using terminal dUTP nucleotide end
      labeling (TUNEL) to detect DNA strand breaks and by counting of apoptotic bodies.
      TUNEL-positive cells were detected in 15.9% (P < 0.01), 8.7% and 7.2% of
      hippocampal cells from fetuses of dams fed the CD, control or CS diets,
      respectively. A similar inverse relationship between dietary intake of choline
      and TUNEL positive cells was detected in an area of cerebral cortex from these
      fetal brain slices. Counts of apoptotic bodies in fetal brain slices correlated
      inversely with choline intake of the mothers (6.2% (P < 0.01), 2.5% and 1.9% of
      hippocampal cells had apoptotic bodies in fetuses of dams fed the CD, control and
      CS diets, respectively). PC12 cells were grown in DMEM/F12 media supplemented
      with 70 microM choline or with 0 microM choline. The number of apoptotic bodies
      in PC12 cells increased when cells were grown in 0 microM choline medium (1.5%; P
      < 0.05) compared to 70 microM choline medium (0.55%). In PC12 cells, TUNEL
      labeling (DNA strand breaks) increased in choline deficient (13.5%, P < 0.05)
      compared to sufficient medium (5.0%). In addition, cleavage of genomic DNA-into
      200 bp internucleosomal fragments was detected in choline-deficient cells. These
      results show that choline deficiency induces-apoptotic cell death in neuronal
      type cells and in whole brain. We suggest that variations in choline availability
      to brain modulate apoptosis rates during development.

PMID- 9263576
TI  - Behavioral changes in rats with early ventral hippocampal damage vary with age at
      damage.
AB  - Our previous work demonstrated that neonatal (on postnatal day 7, PD7)
      excitotoxic damage of the ventral hippocampus (VH) results in delayed emergence
      of behaviors related to dopaminergic (DA) transmission. In this study, the
      developmental effects of VH lesions induced at two other ages were investigated
      in the rat. Ibotenic acid or artificial cerebrospinal fluid was infused into the
      VH of 3- (PD3) or 14- (PD14)-day-old rat pups. Amphetamine-induced (1.5 mg/kg,
      i.p.) locomotor activity was assessed in the sham and lesioned rats prior to
      (PD35) and after puberty (PD56 and PD86). Apomorphine-induced (0.75 mg/kg s.c.)
      stereotypic behaviors were measured on PD56. Similar VH lesions resulted in
      different profiles of behavioral abnormalities depending upon the age at which
      they were induced. The PD3 lesioned rats displayed hyperlocomotion to amphetamine
      only after puberty, while the PD14 lesioned rats manifest hyperlocomotion as
      early as 3 weeks after surgery (at PD35). Moreover, the PD3 lesioned rats tended
      to show more stereotypic behaviors in response to apomorphine than the sham
      operated controls, while the PD14 rats had a profoundly diminished stereotypic
      response. The behavioral changes in the PD3 lesioned rats are reminiscent of
      those previously described in animals lesioned at PD7. In contrast, the deficits
      in the PD14 lesioned animals resemble those seen before in rats lesioned in
      adulthood. These results indicate that the pattern of impairments associated with
      the excitotoxic VH lesion varies with age at lesion, i.e. a similar pattern seems
      to be associated with lesions up to PD7, but not by PD14. To the extent that the
      neonatal VH lesion in the rat models certain phenomenological aspects of
      schizophrenia, including the temporal pattern of symptom onset, these results
      provide evidence that the model requires an early defect in limbic cortical
      development.

PMID- 9263577
TI  - Gliogenesis in postnatal rat optic nerve: LC1 + microglia and S100-beta +
      astrocytes.
AB  - Lipocortin 1 (LC1) and S100-beta, two Ca(2+)-binding proteins that serve as
      specific markers for microglia and astrocytes, respectively, have been used to
      study postnatal gliogenesis in the rat optic nerve. Computerized image analysis
      was used to quantify and map the stained and unstained glia in transverse
      sections (10 microns thick) taken 1-2 mm from the chiasm in optic nerves from rat
      pups at postnatal day 0 (P0), P7, P14, P21, P28, P38 and adults. The number of
      astrocytes was remarkably constant (100 per section) at all ages. Because the
      area of the nerve increases 10-fold from P0 to adult, the population density of
      astrocytes begins al > 5000 mm-2 and drops to 400 mm-2 in the mature nerve;
      however, because the nerve length increases two-fold, the number of astrocytes
      doubles over the same period. In contrast, the number of LC1 + cells per section
      initially is sparse (4 at P0), increases rapidly up to 36 at P21 and levels off
      at 49 in adults. The microglia population density is relatively stable throughout
      development (200-300 mm-2) except during the peak of oligodendroblast apoptosis
      (P21) when it rises to 450 mm-2. Neonatally, LC1 immunoreactivity predominantly
      labels spherical-ameboid cells; but by P28 they are replaced by mature ramified
      microglia. The number of unstained cells (putative oligodendrocytes) per section
      increases from 11 at P0 to a peak of 308 at P21, and declines slightly to 269 in
      adults. While generally confirming concepts of astrocyte and oligodendrocyte
      ontogeny from the literature, the present report adds considerable detail
      regarding microglia, which often have been ignored. Microglia identified by LC1
      immunoreactivity comprise 12% of the glia in adult optic nerve near the chiasm.

PMID- 9263578
TI  - Functional connectivity in the rodent trigeminal pathway grown in vitro.
AB  - In explant cocultures of the rat trigeminal pathway, embryonic trigeminal
      ganglion cells grow their axons into peripheral cutaneous and central nervous
      system targets (R.S. Erzurumlu, S. Jhaveri, Target influences on the morphology
      of trigeminal axons, Exp. Neurol, 135 (1995) 1-16; R.S. Erzurumlu, S. Jhaveri, H.
      Takahashi, R.D.G. McKay, Target-derived influences on axon growth modes in
      explant cocultures of trigeminal neurons, Proc. Natl. Acad. Sci. USA 90 (1993)
      7235-7239). In heterochronic cocultures, composed of embryonic trigeminal
      ganglion, embryonic whisker pad and postnatal brainstem slice, trigeminal axons
      develop arbors and terminal boutons in the brainstem trigeminal nuclei. To
      determine whether these terminal arbors establish functional connections with the
      brainstem neurons, we examined the electrophysiological properties of brainstem
      neurons and their responsiveness to trigeminal ganglion stimulation.
      Intracellular recordings were done in vitro on cells of the trigeminal subnucleus
      interpolaris (SPI) in trigeminal pathway cocultures (E15 whisker pad, E15
      trigeminal ganglion, and postnatal day (PND) 0-2 brainstem slice) or in the SPI
      of acutely prepared brainstem slices. Electrophysiological properties of SPI
      cells in both preparations were virtually identical. The voltage responses of SPI
      neurons to intracellular current injection were highly linear suggesting they
      lacked a number of voltage-dependent conductances. Depolarizing current injection
      produced trains of action potentials with a frequency that varied with stimulus
      intensity. In explant cocultures, electrical activation of the trigeminal
      ganglion evoked EPSPs, and EPSPs coupled with IPSPs in SPI cells. Bicuculline
      blockade of IPSP activity resulted in long lasting EPSPs whose duration increased
      with membrane depolarization. These results show that brainstem trigeminal
      neurons can retain their functional properties in culture and establish
      functional connections with primary sensory afferents.

PMID- 9263579
TI  - No effect of glutamate on metabolic disturbances in hippocampal slices of mature
      fetal guinea pigs after transient in vitro ischemia.
AB  - The involvement of glutamate in the development of cerebral metabolic
      disturbances in mature fetuses after transient ischemia was studied using a
      hippocampal slice model. We investigated the effects of exogenously applied
      glutamate or glutamate antagonists on the recovery of energy metabolism and
      protein synthesis rate (PSR) in hippocampal slices of mature guinea pigs after in
      vitro ischemia. The slices were incubated in a thermostatically controlled flow
      through chamber and gassed with carbogen (95% O2/5% CO2). In vitro ischemia was
      induced by transferring the slices to an aglycemic, artificial cerebrospinal
      fluid (aCSF) equilibrated with 95% N2/5% CO2. In a first set of experiments
      slices were exposed to 10 mM glutamate during a 20-40 min period of in vitro
      ischemia. In a second set slices were incubated in aCSF containing MK-801 (100
      microM) or kynurenic acid (0.5 mM) 30 min before, during and 2 h after in vitro
      ischemia. After a 12 h recovery phase, the concentrations of adenylates in the
      slices were measured by HPLC after extraction with perchloric acid. PSR was
      calculated from the rate of incorporation of [14C]leucine into tissue proteins.
      Neither glutamate nor glutamate antagonists had any effect on the postischemic
      recovery of energy metabolism and PSR when applied during in vitro ischemia. It
      is therefore concluded that glutamate does not play a major role in the
      development of metabolic disturbances in hippocampal slices from mature guinea
      pig fetuses subjected to transient in vitro ischemia.

PMID- 9263580
TI  - Development of the enkephalin-, neurotensin- and somatostatin-like (ENSLI)
      amacrine cells in the chicken retina.
AB  - The development of the enkephalin-, neurotensin- and somatostatin-like
      immunoreactive (ENSLI) amacrine cells in the chicken retina has been investigated
      by radioimmunoassay (RIA) and immunocytochemistry (ICC). By RIA, enkephalin-like
      immunoreactivity (ENK-LI) was detected at embryonic day (E) 5 at only very low
      levels, which gradually increased until E17. From E18 to E21, there was a
      relatively rapid increase in ENK-LI levels, and just after hatching, there was a
      very steep rise. By ICC, the cell bodies of the ENSLI amacrine cells were first
      detected in the inner nuclear layer on E18, with no immunostaining in the inner
      plexiform layer (IPL). On E21, more cells were detected and processes in the IPL
      were visible, but detailed arborisations were not clear. On postnatal day (P) 1,
      the ENSLI amacrine cells showed a morphology similar to that in mature retina in
      both the density of cell bodies and the ramification pattern of processes.
      Antibodies to neurotensin and somatostatin revealed a similar developmental
      pattern. Thus, the three peptides appear to follow a similar developmental
      pattern in the ENSLI amacrine cells, suggesting that the three peptides respond
      similarly to developmental stimuli, just as they are released in parallel in
      response to physiological stimulation from mature ENSLI amacrine cells. After
      hatching, higher levels of ENK-LI were detected by RIA and more ENSLI amacrine
      cell bodies and processes were detected by ICC in animals kept in the light than
      in those kept in the dark. In retinas kept in the light for 12 h, it was found
      that immunoreactive processes in the IPL formed strongly stained patches, but
      this was not observed in retinas kept in the dark for 12 h.

PMID- 9263581
TI  - Developmental profile of NGF immunoreactivity in the rat brain: a possible role
      of NGF in the establishment of cholinergic terminal fields in the hippocampus and
      cortex.
AB  - In the current investigation, we have examined the developmental profile of nerve
      growth factor immunoreactivity (NGF-ir) in the postnatal rat. During the first 3
      weeks after birth, NGF-ir was observed within the hippocampal mossy fiber region,
      where it persists throughout adulthood and appeared transiently within three
      additional zones-the dentate gyrus supragranular zone, the tenia
      tecta/intermediate lateral septum, and the cingulate/retrosplenial cortex. In all
      cases, the appearance of NGF-ir progressed in a rostrocaudal pattern over time. A
      strong correlation was seen between the pattern of NGF-ir and cholinergic
      innervation in the dentate gyrus supragranular zone, both spatially and
      temporally, suggesting that NGF may direct the innervation of cholinergic
      afferents to this region. A spatial correlation was also observed between NGF-ir
      and cholinergic innervation within the retrosplenial cortex and tenia tecta. With
      our current techniques, however, we were unable to determine at what point during
      development the adult-like pattern of cholinergic terminal innervation in these
      regions occurred and, thus, were not able establish a temporal correlation in
      these regions. Within the cingulate cortex, there was no evidence suggesting that
      the developmental appearance of NGF-ir in this region was associated with a
      specific enhancement of cholinergic innervation. Thus, the results of the current
      investigation clearly identify the presence of transiently occurring zones of NGF
      ir during postnatal CNS development, although defining their exact functional
      role will require additional investigation.

PMID- 9263582
TI  - Early behavioral development of mice is affected by staggerer mutation as soon as
      postnatal day three.
AB  - Staggerer is a neurological mutation of mice that affects the development of the
      central nervous system and causes abnormal behaviors. The staggerer cerebellum is
      already abnormal at birth and as the animal grows up there is a progressive loss
      of granule cells which have all disappeared by day 28. The earliest behavioral
      disturbance observed is a motor deficiency which occurs between 10 and 15 days
      i.e. several days later than the appearance of the cortical abnormalities. To
      show that staggerer mutant mice also differ from normal mice in behavioral
      aspects before the age of 10 days, 28 staggerer pups and 246 normal pups aged
      from 1 to 9 days underwent different motor tests. In addition, the number of
      ultrasounds emitted during 40 s was recorded, and the animals were weighted every
      day. Differences between staggerer and normal mice were found as early as 3 days:
      staggerers were less efficient in motor tasks and they weighed less than normal
      mice. Staggerers also differed from normal mice in ultrasound production.

PMID- 9263583
TI  - Expression of eight metabotropic glutamate receptor subtypes during neuronal
      differentiation of P19 embryocarcinoma cells: a study by RT-PCR and in situ
      hybridization.
AB  - Metabotropic glutamate receptors modulate neuronal activity but expression and
      alternative splicing of their subtypes (mGluR1-mGluR8) during early neuronal
      differentiation are essentially unknown. In the mouse embryocarcinoma cell line
      P19, one of the best established systems to study neurogenesis in vitro, it was
      shown by RT-PCR and in situ hybridization that the neuronal differentiation
      process, induced by retinoic acid, is characterized by an early increase in the
      expression of mGluR3, mGluR7 and mGluR8 and a late rise in the mRNA levels of
      mGluR1 and mGluR5, whereas mGluR2 and mGluR4 seem to be constitutively expressed.
      In comparison, in primary embryonic neurons all mGluR subtypes were detected at
      day 3 after plating while primary astrocytes and oligodendrocytes have diverging
      mGluR pattern. In addition, the splicing pattern of mGluR1 and mGluR5 transcripts
      differ remarkably between neural cells in vitro and brain tissue. These data,
      although not comparable to the situation in vivo, might be a hint on so far
      unknown functions of metabotropic glutamate receptors during neuronal
      differentiation.

PMID- 9263584
TI  - Nicotinic and muscarinic cholinergic receptor binding in the human hippocampal
      formation during development and aging.
AB  - High-affinity nicotine, alpha-bungarotoxin (alpha BT) and muscarinic receptor
      binding was measured in the human hippocampal formation in a series of 57 cases
      aged between 24 weeks gestation and 100 years. Changes in nicotine receptor
      binding during development and aging were more striking than differences in alpha
      BT and muscarinic binding. Nicotine binding was higher at the late foetal stage
      than at any other subsequent time in all areas investigated. In the hippocampus a
      fall in binding then occurred within the first six months of life, with little or
      no subsequent fall during aging, whereas in the entorhinal cortex and the
      presubiculum the major loss of nicotine binding occurred after the fourth decade.
      alpha BT binding was significantly elevated in the CA 1 region, but in no other
      region of the hippocampus, in the late foetus, and there was also a fall in alpha
      BT binding in the entorhinal cortex during aging from the second decade. The
      modest changes in total muscarinic binding, which appeared to reflect those in M1
      and M3 + 4 rather than M2 binding, were a rise in the entorhinal cortex between
      the foetal stage and childhood and a tendency for receptors to fall with age in
      the hippocampus and subicular complex. These findings implicate mechanisms
      controlling the expression of nicotinic receptors to a greater extent than
      muscarinic receptors in postnatal development and aging in the human hippocampus.

PMID- 9263585
TI  - Influence of the neuropeptide somatostatin on the development of dendritic
      morphology: a cysteamine-depletion study in the rat auditory brainstem.
AB  - We investigated the functional role of somatostatin during early ontogeny of the
      brain, when the neuropeptide as well as its receptors are heavily expressed in
      the auditory brainstem. Rat pups received a daily injection of cysteamine which,
      when applied at low concentrations, most selectively depletes somatostatin.
      Neurons from the lateral superior olive, an auditory brainstem nucleus which
      transiently receives a dense somatostatinergic input, were intracellularly
      labeled at postnatal day 14 or 18. The dendritic morphology of these neurons was
      then analyzed quantitatively and compared with neurons from controls. Cysteamine
      treatment induced a reduction of the number of dendritic end points by more than
      50%. At postnatal day 14, for example, controls and somatostatin-depleted animals
      had an average of 58 and 28 end points, respectively. The number of primary
      dendrites was also significantly reduced by cysteamine. In contrast, the size of
      the somata, the orientation of the dendritic trees within the lateral superior
      olive, the dendritic areas, and the cross-sectional size of the lateral superior
      olive were not altered. These results indicate that somatostatin depletion during
      early development has profound effects on the maturation of dendritic morphology.
      The selective influence on the dendritic trees suggests that somatostatin acts as
      an endogenous trophic peptide and promotes the achievement of dendritic
      complexity.

PMID- 9263586
TI  - Acceleration of neuronal maturation of P19 cells by increasing culture density.
AB  - P19 embryonal carcinoma cells differentiate into neurons, astrocytes, and
      fibroblast-like cells following induction with retinoic acid. The mature neurons
      are capable of neurotransmitter release, and from functional synapses. We have
      previously shown that high culture density suppresses the cholinergic phenotype
      of P19 neurons. Here we demonstrate that increasing culture density accelerates
      the maturation of P19 neurons in a continuous manner. This is manifested by
      several criteria: increased efficiency of evoked [3H]aspartate release; decreased
      level of basal release; up-regulation of synaptic vesicle proteins; increased
      neurite outgrowth rate; and earlier segregation of axons and dendrites. While
      glutamate release is enhanced in dense cultures, the efficiency of [3H]GABA
      release is hardly affected, suggesting that P19 GABAergic neurons are not
      affected by culture density. The acceleration of neuronal maturation in dense
      cultures is also exhibited by the ability of dense, but not sparse cultures to
      release [3H]aspartate at an earlier day of differentiation. Furthermore, density
      effects are monitored already a few hours after plating the cultures, when
      neurite length in dense cultures is several fold higher than in sparse cultures.
      This indicates that commitment to a faster and coordinated maturation process
      occurs already very early during P19 neuronal differentiation.

PMID- 9263587
TI  - Postnatal neurogenesis in the telencephalon of turtles: evidence for nonradial
      migration of new neurons from distant proliferative ventricular zones to the
      olfactory bulbs.
AB  - Postnatal neurogenesis in the the turtle telencephalon was investigated by using
      bromodeoxyuridine immunocytochemistry and [3H]thymidine autoradiography. Red
      eared slider turtles Trachemys scripta elegans (Cryptodira, Emydidae) 2-3 months
      old were injected with the thymidine analogue 5'-bromodeoxyuridine (BrdU) and
      allowed to survive for 7, 30, 90, and 180 days. Results indicate that cells in
      the walls of the lateral ventricles continue to proliferate postnatally. Shortly
      after BrdU treatment (seven days) most labelled cells were found in the walls of
      the lateral ventricles (ventricular zone: VZ). Labelled cells were particularly
      abundant in and around the ventricular sulci. The same pattern of labelling was
      found in the telencephalon of juvenile turtles (> two years old) injected with
      BrdU and killed seven day later, suggesting that the proliferative activity
      continues in the telencephalic VZ of turtles during juvenile stages of life and
      possibly into adulthood. With longer survival periods after BrdU administration
      (30, 90, and 180 days), the VZ of the telencephalon showed a similar pattern of
      labelling to that found at seven days. Furthermore, with survival periods of 90
      and 180 days labelled cells resembling neurons were found in most telencephalic
      regions. The largest numbers of these putative neurons were found in the
      olfactory bulbs. By using [3H]thymidine autoradiography combined with electron
      microscopy these postnatally generated cells were confirmed as neurons. We
      conclude that postnatal neurogenesis occurs in the turtle telencephalon. This
      process is most prominent in the olfactory bulbs. From the pattern of
      proliferation of neuronal precursors in the VZ we infer that neurons recruited
      postnatally into the olfactory bulbs come from distant proliferative VZs in the
      walls of the lateral ventricles.

PMID- 9263588
TI  - Development of HVA and LVA calcium currents in pyramidal CA1 neurons in the
      hippocampus of the rat.
AB  - High voltage activated (HVA) and low voltage activated (LVA) calcium currents
      were recorded in acutely dissociated CA1 hippocampal pyramidal neurons of the rat
      during the first three postnatal weeks as well as in adults. Measured in whole
      cell voltage clamp the amplitude of the HVA calcium current increased steadily
      and reached adult values after 20 postnatal days (P20). Using the perforated
      patch configuration with amphotericin B the amplitude of the HVA component was
      more than five times smaller, but the time course of development was the same.
      The LVA component also increased with age but reached adult values already around
      P13. The amplitude and developmental pattern of this component were not different
      when measured with the perforated patch technique. The results indicate a
      different role for intracellular modulators on these calcium currents, but
      exclude them as important factors in the developmental pattern. The fast
      development of the LVA component could lead to calcium dependent action
      potentials (and calcium spikes) in immature cells. The complex developmental
      pattern of the relative amplitude of the two currents will either lead to
      specific variations in the intracellular calcium homeostasis or will have to be
      accompanied by an adequate developmental pattern of buffering and extrusion
      mechanisms.

PMID- 9263589
TI  - Early generation of glia in the intermediate zone of the developing cerebral
      cortex.
AB  - Radial glia are present at the earliest stage of cerebral cortical development,
      and later they transform into astrocytes. Other glial cells including astrocytes
      and oligodendrocytes are thought to appear only after neuron generation is
      complete and the cortical layers are formed. Little is known of when and where
      microglia enter the central nervous system and proliferate. We addressed the
      question of the origin of these three glial cell types in the developing ferret
      cerebral cortex. We assessed the temporal pattern of glial cell division by
      administering [3H]thymidine to label cells in S phase, and by using survival
      periods of 1-2 h to label dividing cells in situ. Labeled cells were identified
      in the developing intermediate zone of the ferret cerebral wall. These cells were
      present at E28, and reached a maximum number at P1. Double labeling experiments
      identified these cells as astrocytes, oligodendrocytes or microglia. None of the
      dividing cells expressed neuronal markers. These data show that all three types
      of glia are generated in the developing subcortical white matter, and that glial
      progenitors are present in the intermediate zone as soon as it becomes a
      recognizable structure. These data also show that the period of glial generation
      overlaps extensively with the period of neuron generation, since neuron
      generation is not complete until the end of the second postnatal week in the
      ferret.

PMID- 9263590
TI  - Retinal activity regulates developmental switches in functional properties and
      ifenprodil sensitivity of NMDA receptors in the lateral geniculate nucleus.
AB  - Previous studies have shown that marked changes occur in the kinetic properties
      of N-methyl-D-aspartate (NMDA) receptors during development of the visual
      pathways. In the lateral geniculate nucleus (LGN) of the ferret, excitatory
      postsynaptic currents (EPSCs) induced by activation of NMDA receptors display a
      very slow decay time during the first postnatal month, then become shorter in
      duration following eye-opening (around postnatal day 32; P32). In view of the
      critical role that NMDA receptors play in activity-dependent refinement of visual
      connections during development, we have examined the mechanisms that underlie
      these changes and how they are regulated. To examine the role of retinal
      activity, whole-cell recordings were conducted in the LGN slice preparation
      obtained from normal ferrets and ferrets treated with continuous intraocular
      application of tetrodotoxin (TTX) from P25 until the time of recording. Blockade
      of ganglion cell activity with TTX prevented the changes in decay rate of the
      postsynaptic current induced by NMDA receptors. Treated animals older than P40
      had NMDA-EPSCs markedly longer in duration than normal animals at a similar age,
      resembling responses present in normal newborn animals. To examine whether
      changes in subunit composition of the NMDA receptor may contribute to the
      maturation of its kinetic properties, we used the antagonist ifenprodil, which
      produces selective inhibition of heteromeric NMDA receptors containing the NR-2B
      subunit. Ifenprodil induced profound inhibition of NMDA receptor activity in
      normal young animals and TTX-treated mature animals, but substantially less
      inhibition in normal mature animals. These findings indicate that retinal
      activity is required for the developmental switch from a juvenile form of the
      NMDA receptor to a more mature form, possibly affecting NR2 subunit expression.

PMID- 9263591
TI  - Transient expression of NADPH-diaphorase/nitric oxide synthase in the paratenial
      nucleus of the rat thalamus.
AB  - The distribution pattern of nitric oxide synthesizing neurons was studied in the
      paratenial nucleus throughout the rat development using the NADPH-diaphorase (ND)
      histochemical method and nitric oxide synthase (NOS) immunocytochemistry. The
      onset of ND/NOS activity in the paratenial nucleus was detected in the postnatal
      life day 1. Until the postnatal stage 4, a quick increase in the number and
      staining intensity of the ND/NOS positive neurons was observed. From postnatal
      day 4 to postnatal day 6, these variations continued slowly, whereas an increase
      in the neuronal size was evident. In these stages, densely packed ND/NOS-labeled
      neurons were observed. From stages 6 to 10, the ND/NOS-positive elements
      demonstrated similar number, size, and staining intensity. These cells had medium
      size, variable morphology and showed reaction product in the cell bodies and, at
      most, their proximal dendrites. After postnatal day 10, a quick decrease in the
      staining intensity and in the number of ND/NOS-labeled elements was detected,
      although no changes were observed in their morphological characteristics.
      Postnatal day 15 was the last developmental stage studied in which ND/NOS
      positive elements were observed. Finally, the paratenial nucleus did not present
      ND/NOS-positive elements in adult animals. This transient expression of the
      ND/NOS-activity suggests a role of nitric oxide in the reorganization of the
      paratenial nucleus during the first postnatal fortnight.

PMID- 9263592
TI  - Differential laminin isoform expression in the developing rat olfactory system.
AB  - Members of the laminin family influence mammalian cells in a variety of ways,
      mediating adhesion, proliferation, migration, and growth of neuronal processes.
      Specific laminin domains act through a number of cellular interaction sites to
      mediate these activities. In the developing olfactory system, axons grow from the
      olfactory epithelium to synaptic sites in the olfactory bulb a matrix rich in
      laminins and known mediators of laminin-axon interactions include integrins and a
      galectin-1/glycoconjugate adhesion system. Using biochemistry,
      immunocytochemistry, and in situ hybridization, we identified alpha 2, alpha 3,
      beta 1, beta 2 and gamma 1 laminin isoforms in the late embryonic and neonatal
      rat olfactory system. However, alpha 1-containing laminin could not be detected
      in association with olfactory neurons. Immunocytochemistry revealed that beta 2
      laminin is preferentially expressed in the ventral and lateral nerve layer of the
      olfactory bulb and in the main olfactory axon tracks, but is undetectable in the
      accessory system during embryonic and early postnatal development. In contrast,
      beta 1 and gamma 1 laminins are evenly distributed throughout the olfactory bulb
      and in both the main and accessory olfactory axon tracks. The differential
      localization of laminin chains in vivo is likely to have functional significance
      for the development and maintenance of the olfactory system.

PMID- 9263593
TI  - Involvement of phosphatidylinositol-3 kinase in prevention of low K(+)-induced
      apoptosis of cerebellar granule neurons.
AB  - Cerebellar granule neurons obtained from 9-day-old rats die in an apoptotic
      manner when cultured in serum-free medium containing a low concentration of
      potassium (5 mM). A high concentration of potassium (26 mM) in the culture medium
      and BDNF can effectively prevent this apoptosis. The survival effects of high
      potassium and BDNF were additive, and the effect of high potassium was not
      blocked by addition of anti-BDNF antibody. These observations indicated that
      these survival effects were independent. To examine which molecules are involved
      in the survival pathway induced by BDNF or high K+, we used wortmannin, a
      specific inhibitor of PI-3 kinase. Wortmannin blocked the survival effects of
      both BDNF and high K+ on cerebellar granule neurons. Furthermore, in vitro PI-3
      kinase assay showed that treatment with BDNF or high K+ induced PI-3 kinase
      activity, which was diminished by addition of wortmannin. These results indicate
      that different survival-promoting agents, BDNF and high K+, can prevent apoptosis
      in cerebellar granule neurons via a common enzyme, PI-3 kinase.

PMID- 9263594
TI  - Retrosplenial/presubicular continuum in primates: a developmental approach in
      fetal macaques using neurotensin and parvalbumin as markers.
AB  - In spite of numerous hodological and neuropsychological studies emphasizing the
      multimodal connections and integrative functions of the retrosplenial cortex in
      primates, the precise fate of its caudoventral extent and the composition of the
      merging area with the hippocampal formation remain a matter of debate. We
      reported previously how the anlage of the retrosplenial cortex merges with the
      immature presubicular zone in the fetal rhesus monkey at the end of the first
      trimester of gestation. In the present study, this caudal area was further
      defined on a chemoarchitectonic basis, particularly during the late prenatal and
      perinatal stages, which correspond to the development of the cingulate sulcus and
      temporal gyri, and the differentiation of the retrosplenial/subicular complex.
      Neurotensin (NT), a pyramidal cell marker in the limbic cortex, and parvalbumin
      (PV), a marker of a subset of inhibitory local circuit neurons in the hippocampal
      formation, were used as immunocytochemical markers. According to distinct
      chemoarchitectural patterns, (1) areas 29 l and 29 m of the retrosplenial cortex
      formed a triangle-shaped ventral expansion which merged with a similar but dorsal
      expansion of the pre/parasubicular fields. A temporal extension of area 29 m down
      to area TH could not be detected. The pre/parasubiculum contributed with area 29
      m to the lateral bank of the calcarine sulcus as far as the most caudal extent of
      the hippocampal formation. (2) The lamina principalis interna of the presubiculum
      was well individualized and did not appear as a simple horizontal shift of
      adjoining fields. (3) NT and PV displayed a distinct temporal profile of
      development. NT was already expressed in the pyramidal cells of the prospective
      retrosplenial cortex and ventral hippocampal formation at E47 (term 165 days).
      Major pathways of the hippocampal formation and retrosplenial cortex (fimbria,
      fornix, angular and cingulum bundles) were progressively labeled indicating early
      developing projections. A large set of NT-positive afferents reached the
      retrosplenial cortex between E114 and E120. Their laminar distribution was
      compatible with a thalamic or a subicular origin. (4) The development of PV
      expression was delayed until the last quarter of gestation, supporting its
      proposal as a signal of functional onset. The developmental fate and the
      particular connections of the presubiculum suggest that its functional importance
      should be further investigated during infancy and adulthood.

PMID- 9263595
TI  - Immunocytochemical localization of a novel radial glial intermediate filament
      protein.
AB  - We have examined by immunocytochemistry the subcellular localization of a chick
      radial glial protein, named transitin, that by molecular cloning has been shown
      to be a novel member of the intermediate filament protein superfamily. In
      astrocytes cultured from E10 chick brain, transitin is localized to the
      intermediate filament network in accordance with its structural properties. Using
      confocal microscopy we examined the expression of transitin, vimentin and glial
      fibrillary acidic protein (GFAP) in cultured astrocytes, and show that transitin
      co-distributes with these other glial intermediate filament proteins. The
      expression of transitin, vimentin and GFAP was also compared in embryonic chick
      spinal cord and brain radial glia, with these studies showing that these
      intermediate filament proteins display distinct expression patterns during CNS
      development. Of particular note is the absence of vimentin and GFAP in spinal
      cord midline radial glia that express transitin protein, and a transient
      expression of transitin in brain midline radial glia that continue to express
      vimentin. Our studies presented here therefore indicate that transitin, a novel
      radial glial intermediate filament protein, may have functions that are unrelated
      to GFAP or vimentin during CNS development, since transitin is localized to the
      processes of midline radial glia and is transiently expressed during chick CNS
      development.

PMID- 9263596
TI  - Changes in proenkephalin gene expression in the developing hamster.
AB  - Proenkephalin (Penk) gene expression is high in the adult hamster adrenal medulla
      and it is comparable to that found in both the hamster and rat striatum. In
      addition, Penk gene expression in the hamster adrenal medulla is more typical of
      adult mammalian adrenals than the rat. Since the nature of Penk gene expression
      in the developing hamster adrenal is not known, it was examined and compared to
      that found in the striatum were adult levels in the adrenal and striatum are
      similar. The results show that Penk gene expression progressively increases in
      the developing hamster adrenal to peak on postnatal day 4. There is then a small
      decline to adult levels by postnatal day 12 when the morphology of the developing
      adrenal resembles the adult. Functional splanchnic nerve activity, as assessed by
      the ability of reserpine to induce increases in adrenal tyrosine hydroxylase
      mRNA, is not present until after postnatal day 4. Therefore, early increases in
      Penk gene expression are independent of splanchnic nerve activity. Adrenal EC
      peptides resulting from the developmental increases in Penk gene expression
      appear to be unprocessed and proenkephalin-like. This is based on the very low
      levels of free enkephalin (met-enkephalin) detected in the adrenals from both
      newborn and adult hamsters (1-5% of total EC peptide levels). In the developing
      hamster striatum, Penk gene expression remains low and unchanged until postnatal
      day 4 and increases six-fold by adulthood. Free enkephalin (met-enkephalin)
      levels remain high (between 36 and 88% of total EC peptide levels) in the
      developing and adult hamster striatum. Therefore the results show early increases
      in adrenal Penk gene expression in the developing hamster that are independent of
      splanchnic nerve activity and adult Penk gene expression which is high and
      dependent on splanchnic nerve activity. This differs from what is observed in the
      frequently studied rat. However, developmental changes in the hamster striatum
      are similar to those in the rat.

PMID- 9263597
TI  - Myelin basic protein immunoreactivity in the internal capsule of neonates from
      rats on a low iodine intake or on methylmercaptoimidazole (MMI).
AB  - Rats fed on low iodine diets (LIDs) result in a normal circulating level of
      triiodothyronine (T3), a low level of thyroxine (T4) and an elevated thyroid
      stimulating hormone (TSH). These changes are similar to those observed in
      habitants who live in iodine-deficient areas and different from those observed
      when the hypothyroidism is produced by goitrogens. To study the effects of LID or
      goitrogens on the myelin basic protein (MBP) immunoreactivity (MBP-ir) during the
      myelination of the internal capsule, one group of experimental female rats was
      fed on an LID, and another group received a standard laboratory diet with
      methylmercaptoimidazole (MMI) added in the drinking water. Animals fed on a
      standard laboratory diet and animals fed on an LID supplemented with KI were used
      as controls. At P10, the MMI treatment has produced a more marked decrease in the
      surface density of MBP-ir processes with respect to controls than that produced
      in the LID animals. This decrease was correlated with the cerebral concentrations
      of triiodothyronine (T3) we found. During the postnatal development, a recovery
      in the levels of the surface density with respect to controls was observed in
      both experimental groups. The recovery occurred by P20 in the LID group and by
      P32 in the MMI rats.

PMID- 9263598
TI  - The growth-associated protein GAP-43 is specifically expressed in tyrosine
      hydroxylase-positive cells of the rat retina.
AB  - In the adult retina, the growth-associated protein GAP-43 is exclusively present
      in three distinct sublaminae of the inner plexiform layer. During postnatal
      development, it is transiently expressed in the optic nerve fibers. No
      conclusions about the GAP-43 expressing cells can be derived from
      immunohistochemical stainings because GAP-43 protein is rapidly transported into
      the distal neuronal processes. We have combined immunohistochemistry to study the
      protein expression of GAP-43 and non-radioactive in situ hybridization to study
      the cellular expression of GAP-43 in the rat retina. We have found that in the
      mature retina GAP-43 mRNA is present only in retinal ganglion cells and in a
      small subset of cells of the inner nuclear layer. During postnatal development,
      no cells besides retinal ganglion cells and a subpopulation of cells in the inner
      nuclear layer express GAP-43 mRNA. Double staining experiments with tyrosine
      hydroxylase (TH) immunohistochemistry and GAP-43 in situ hybridization showed
      that GAP-43 expressing cells in the inner nuclear layer are immunoreactive for
      TH. They are most probably dopaminergic amacrine cells. Our results show that GAP
      43 expression in the retina is restricted to very few cell types. They suggest
      that TH-positive cells (probably dopaminergic amacrine cells) retain a higher
      degree of structural plasticity in the adult retina.

PMID- 9263599
TI  - Activation of the type 2 adrenal steroid receptor can rescue granule cells from
      death during development.
AB  - To determine whether activation of the type 2 adrenal steroid receptor affects
      granule cell death in the developing dentate gyrus, we treated rat pups with the
      type 2 receptor agonist RU28362 and examined degenerating cells using terminal
      deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) and
      Nissl staining. RU28362 administration decreased the numbers of degenerating
      granule cells suggesting that type 2 receptor activation can rescue granule cells
      from degeneration.

PMID- 9263600
TI  - Interactions of corticosterone and embryonic light deprivation on memory
      retention in day-old chicks.
AB  - Corticosterone, injected embryonically into eggs hatched in the dark, improved
      retention for a weak passive avoidance task in day-old chicks, the optimal time
      points for injection were days E19 to E20, resembling those found previously for
      light exposure, suggesting possible interactions between light and corticosterone
      during late embryonic development with consequent effects on post-hatch
      behaviour.

PMID- 9263601
TI  - Sexually dimorphic effects of anti-NGF treatment in neonatal rats.
AB  - This study investigated how chronic perinatal reduction of nerve growth factor
      (NGF) affected brain cholinergic markers in the two sexes. Rats received anti-NGF
      on postnatal days (PNDs) 2-12, and choline acetyltransferase (ChAT) activity was
      measured on PND 16. Anti-NGF significantly reduced cortical ChAT activity in
      males, but not in females; no sex-dependent effects were found in hippocampus or
      striatum. These data suggest sexual dimorphism in cholinergic responsiveness to
      NGF.

PMID- 9263602
TI  - Developmental differences in endplate response to P-type calcium channel blockade
      in the rat diaphragm.
AB  - Endplate potentials (epps) were recorded intracellularly from single diaphragm
      fibers of newborn (7-10 days, n = 11) and older (24-30 days, n = 11) rats in the
      presence of 100 nM omega-agatoxin IVA, a P-type Ca2+ channel blocker. The muscle
      was stimulated via the phrenic nerve for 1 s at 40 Hz. In both age groups epp
      amplitude decreased with omega-agatoxin, however the decrease was greater in the
      older group (mean = 60% of control vs. 40% of control in the younger group). A
      larger number of fibers in the older group (84% vs. 54% in the young) showed a >
      or = 50% decrease in epp amplitude. These data suggest that although P-type Ca2+
      channels are present in the immature presynaptic nerve terminals at the
      neuromuscular junction, functional maturation of these channels occurs with
      development. This may contribute to the susceptibility to neuromuscular
      transmission failure in the newborn diaphragm.

PMID- 9263603
TI  - Carbon monoxide formation in the guinea pig hippocampus: ontogeny and effect of
      in vitro ethanol exposure.
AB  - Carbon monoxide (CO) is considered to be a novel neuronal messenger in the brain,
      similar to nitric oxide. The ontogeny of CO formation in transverse hippocampal
      slices of the guinea pig was elucidated at selected prenatal and postnatal ages,
      and the effect of in vitro ethanol exposure on hippocampal CO formation was
      determined. There was a higher rate of hippocampal CO formation in the fetus at
      gestational day (GD) 50 and GD 62 (term, about GD 68) compared with the adult. In
      vitro ethanol exposure (50 and 100 mM) decreased hippocampal CO formation in the
      GD 62 fetus, which was prevented by incubation with 500 microM L-glutamate.

PMID- 9263604
TI  - Developmental switch in phenotypic expression of preproenkephalin mRNA and 45Ca2+
      accumulation following kainate-induced status epilepticus.
AB  - Kainic acid-induced status epilepticus results in delayed degeneration of CA3
      hippocampal neurons in the mature but not immature rat hippocampus. In adult
      rats, the putative opioid precursor, preproenkephalin (PPE) mRNA increases in the
      dentate gyrus (DG), a region resistant to damage, following continuous limbic
      seizures. To explore why the immature brain is resistant to seizure-induced
      damage, the regional distribution of PPE mRNA expression and 45Ca2+ accumulation
      were compared in postnatal day 14 (P14) pup, and adult hippocampus at 5-6 h after
      kainate-induced status epilepticus. Inverted patterns of PPE expression and Ca2+
      uptake were observed at the two ages. In P14 pups, PPE mRNA expression increased
      in DG and escalated in CA3, regions where 45Ca2+ accumulations were absent. In
      adult rats, PPE mRNA expression increased only in DG; 45Ca2+ labeling was
      predominant in CA3a,c and absent in DG. Pronounced increases in enkephalin
      neuropeptide synthesis in immature CA3 neurons may reduce glutamate release
      presynaptically and also prevent voltage-gated Ca2+ uptake into these neurons
      despite recurrent seizure activity. Opioid-mediated inhibition may provide an
      explanation for the resistance of the immature CA3 region to seizure-induced
      damage.

PMID- 9263605
TI  - NGF antibodies impair long-term depression at the mossy fibre-CA3 synapse in the
      developing hippocampus.
AB  - Nerve growth factor (NGF) and other neurotrophins are proteins involved in
      neuronal survival and differentiation. Much experimental evidence is now drawing
      attention into a role of neurotrophins in activity-dependent synaptic plasticity
      processes. We now show that slices from rats chronically deprived of NGF, by
      intraventricular injection of alpha D11 hybridoma cells, which produce monoclonal
      antibodies against NGF, display a reduced probability of induction of long-term
      depression at the mossy fibre-CA3 synapse.

PMID- 9263607
TI  - Ipriflavone: background.

PMID- 9263606
TI  - Serotonin facilitates synaptic plasticity in kitten visual cortex: an in vitro
      study.
AB  - We have addressed the role of serotonin-2C (5-HT2C) receptors in the development
      and maintenance of synaptic plasticity in the kitten visual cortex. In visual
      cortical slices, taken from 40- to 80-day-old kittens, bath application of
      serotonin markedly facilitated the induction of both long-term depression (LTD)
      and long-term potentiation (LTP). Field potential responses to white matter
      stimulation were recorded from layer IV after a regime of low frequency
      stimulation (LFS; 1 Hz, 15 min), which reliably induced LTP or LTD in younger
      kittens (less than 30 days of age). At 40-80 days, this protocol almost never
      induced LTD or LTP in layer IV. However, in 50% of the visual cortical slices
      studied in 40-80-day-old kittens, LTD or LTP was induced, if serotonin (1 or 10
      microM) was co-applied with LFS. No such serotonin facilitation of long-term
      plasticity was ever detected in > 120-day-old animals, indicating that serotonin
      facilitates synaptic plasticity within a defined period of visual cortical
      development. Serotonergic 5-HT2C receptors are likely to contribute to the
      synaptic plasticity observed in layer IV, since mesulergine, an antagonist of the
      5-HT2C receptor, completely blocked synaptic modifications induced by the
      combination of low frequency stimulation and serotonin application.

PMID- 9263608
TI  - Natural and synthetic isoflavones in the prevention and treatment of chronic
      diseases.
AB  - The evidence that natural isoflavones protect against several chronic diseases is
      both observational and experimental. In humans, epidemiologic findings clearly
      show a higher incidence of some common types of cancer (i.e., breast, prostate,
      and colon) and of coronary heart diseases in Western populations exposed to
      limited amounts of soybean isoflavones (i.e., genistein, daidzein) in the diet.
      Further evidence for cancer and cardiac protection and antiatherogenic effects
      resulting from soybean isoflavones administration has been noted in various
      experimental animal models. Isoflavones may also prevent postmenopausal bone loss
      and osteoporosis. In fact, genistein has been reported to be as active as
      estrogens in maintaining bone mass in ovariectomized rats. Moreover, the
      synthetic isoflavone derivative ipriflavone is able to reduce bone loss in
      various types of animal models of experimental osteoporosis providing a rationale
      on its use in the prevention and treatment of postmenopausal and senile
      osteoporosis in humans. The mechanism through which isoflavones may exert the
      above-mentioned effects seems to depend, at least in part, on their mixed
      estrogen agonist-antagonist properties. An alternative hypothetical mechanism
      could derive from other biochemical actions of isoflavones such as inhibition of
      enzymatic activity, in particular protein kinases, or activation of an "orphan"
      receptor distinct from the estrogen type I receptor.

PMID- 9263609
TI  - Ipriflavone inhibits bone resorption in intact and ovariectomized rats.
AB  - The aim of this study was to investigate the possible inhibitory effect of
      ipriflavone on bone resorption in rats. For this purpose, 10-week-old, intact and
      ovariectomized (OVX) rats, prelabeled from birth with [3H]-tetracycline, were
      used. Bone resorption was monitored by measuring the urinary excretion of [3H].
      The animals were fed a purified diet devoid of naturally occurring flavonoids. In
      the intact rats, the daily meal was given either as a single portion or divided
      into four portions, a procedure known to lead by itself to a decrease in bone
      resorption. Ipriflavone, given 7 days after OVX at the dose of 400 mg/kg B.W.
      daily mixed with the food, led within 2-3 days to a significant decrease in bone
      resorption equivalent to that of 27.2 micrograms/kg s.c. of 17 beta-estradiol.
      The inhibition was sustained for the length of the experiment, up to 21 days.
      Ipriflavone given 7 days before OVX prevented the increase in bone resorption
      induced by castration, the effect being dose-dependent between 50 and 400 mg/kg
      B.W. In contrast to 17 beta-estradiol, a 5-week treatment with ipriflavone failed
      to prevent the OVX-induced uterine atrophy. Significant inhibition of bone
      resorption was also seen in intact animals, provided they rapidly ingested the
      daily meal. Actually, the decrease in bone resorption induced by portioning the
      daily food masked the inhibitory effect of ipriflavone in intact animals. In
      conclusion, ipriflavone can decrease bone resorption in both intact and OVX
      animals given a purified diet as a single daily meal. In the OVX model,
      ipriflavone mimics the osteoprotective effect of estrogen. However, the lack of a
      uterotropic effect suggests that the compound can discriminate between bone and
      reproductive tissues.

PMID- 9263610
TI  - In vitro and in vivo effects of ipriflavone on bone formation and bone
      biomechanics.
AB  - Ipriflavone (i.p.) positively affects bone density in postmenopausal
      osteoporosis, primarily by inhibiting bone resorption. Using in vitro models of
      human osteoblast differentiation, we have observed that i.p. and some of its
      metabolites stimulate the expression of bone sialoprotein, decorin, and type I
      collagen, and facilitate the deposition of mineralized matrix. This suggests that
      i.p. may stimulate bone formation in addition to its antiresorptive activity. To
      assess whether these effects translate into an improved bone "quality" in vivo,
      we measured biomechanical properties, mineral composition, and crystallinity of
      femurs of 12-week-old, male, Sprague-Dawley rats treated with i.p. for 1 month.
      i.p. significantly decreased vibration damping, an index of strain energy loss.
      Because vibration damping increases as bone porosity increases, the results
      indicate that i.p.-treated bones acquired a higher capacity to withstand dynamic
      stress. In fact, 1.5-fold higher energy was required to fracture femurs of i.p.
      treated rats after a single supramaximal impact. i.p. also increased BMD,
      assessed by both volume displacement and ash analysis, whereas the relative
      contents of Ca, P, and Mg in the ashes were not affected. Thus, no gross
      abnormalities in mineral composition of bone occurred after i.p. administration.
      As a measure of bone crystallinity, X-ray diffraction analysis was performed. The
      broadening parameter beta 1/2 for the (310) and (002) reflections was not
      significantly different between i.p.-treated and control animals. Similarly,
      there were no differences in serum levels of Ca, Mg, alkaline phosphatase, and
      type I collagen telopeptides between treated and control animals at the end of
      the study. Therefore, 1-month treatment with i.p. increased bone density and
      improved the biomechanical properties of adult male rat bones without altering
      mineral composition or bone crystallinity.

PMID- 9263611
TI  - Ipriflavone prevents the loss of bone mass in pharmacological menopause induced
      by GnRH-agonists.
AB  - In a double-blind, placebo controlled study, ipriflavone (600 mg/day, T.D.D.) or
      identical placebo tablets were given with 500 mg/day of calcium to patients
      treated with the gonadotropin hormone-releasing hormone agonist (Gn-RH-A)
      leuproreline acetate, 3.75 mg every 30 days for 6 months. In placebo-treated
      subjects (n = 39), urinary hydroxyproline excretion and plasma osteocalcin levels
      showed a significant (P < 0.01 and P < 0.05, respectively) increase, whereas
      spine bone density and total body bone density significantly (P < 0.001 and P <
      0.05, respectively) decreased after 3 and 6 months of GnRH-A administration.
      Conversely, in the ipriflavone-treated group (n = 39), no significant difference
      in bone markers and bone density was evidenced. These data indicate that
      ipriflavone can restrain the bone remodeling processes and prevent the rapid bone
      loss that follows medically induced hypogonadism.

PMID- 9263612
TI  - Effect of chronic treatment with ipriflavone in postmenopausal women with low
      bone mass.
AB  - We present the results of two multicenter, double-blind, placebo-controlled, 2
      year studies to evaluate the efficacy and tolerability of ipriflavone in
      postmenopausal women (PMW) with low bone mass. 453 PMW (aged 50-65 years) with a
      vertebral (VMD) or radial (RMD) mineral density value 1 SD lower compared with
      age-matched controls, were randomly selected to receive oral ipriflavone (200 mg
      T.I.D. at meals) or matching placebo, plus 1 g oral calcium daily. Vertebral
      (study A, by dual X-ray absorptiometry-DXA) and radial (study B, by dual photon
      absorptiometry-DPA) bone density, serum bone Gla-protein (BGP), and urinary
      hydroxyproline/creatinine (HOP/Cr) were measured every 6 months. In both studies,
      the Valid Completers (VC) analysis showed a maintenance of bone mass in
      ipriflavone-treated women, whereas in the placebo group, bone mineral density
      (BMD) was significantly decreased. The final outcome was a bone-sparing effect of
      1.6% in study A, and of 3.5% in study B after 2 years. The Intention to Treat
      (ITT) analysis confirmed the decrease in the placebo group, with no changes in
      ipriflavone-treated women. A significant (P < 0.05) between-treatment difference
      was found in both studies. Biochemical markers of bone turnover decreased in
      patients treated with ipriflavone, thus suggesting a reduction of bone turnover
      rate. Twenty-six women treated with ipriflavone and 28 receiving the placebo
      dropped out because of side effects, mainly gastrointestinal. The compliance to
      the oral long-term treatment was good. The results of these studies show that
      ipriflavone is able to prevent both axial and peripheral bone loss in PMW with
      low bone mass, and is well tolerated.

PMID- 9263613
TI  - Efficacy of ipriflavone in established osteoporosis and long-term safety.
AB  - Ipriflavone (i.p.), an isoflavone derivative, is currently used in several
      countries for prevention and treatment of osteoporosis. Recently, 149 elderly,
      osteoporotic women (65-79 years) with prevalent vertebral fractures were enrolled
      in two Italian, multicenter, double-blind, 2-year studies. Women were randomly
      allocated to receive either oral i.p. (200 mg T.I.D. at meals) or matching
      placebo, plus 1 g oral calcium daily. One hundred eleven subjects completed the 2
      year treatment period. A significant increase in forearm bone mineral density
      (BMD), measured by dual photon absorptiometry (DPA), was obtained after i.p.
      treatment. Women receiving the placebo showed only a limited bone loss during the
      treatment period, probably due to calcium supplement; however, a significant
      between-treatment difference was obtained in both studies. Urinary hydroxyproline
      was significantly decreased in i.p.-treated patients, suggesting a reduction in
      bone turnover rate. A reduction of incident vertebral fractures was observed in
      i.p.-treated women compared with control subjects. A significant improvement of
      bone pain and mobility has also been pointed out in one of the studies. To date,
      2769 patients have been treated with i.p., for a total of 3132 patient/years, in
      60 clinical studies performed in Italy, Japan, and Hungary and reviewed for long
      term safety assessment. The incidence of adverse reactions in ipriflavone-treated
      patients (14.5%) was similar to that observed in subjects receiving the placebo
      (16.1%). Side effects were mainly gastrointestinal. Few patients presented
      reversible modifications of laboratory parameters. The data from the above
      studies show that long-term treatment with i.p. may be considered safe, and may
      increase bone density and possibly prevent fractures in elderly patients with
      established osteoporosis.

PMID- 9263614
TI  - Design for an ipriflavone multicenter European fracture study.
AB  - In order to investigate the efficacy of ipriflavone (i.p.) on the prevention of
      vertebral fractures and the effect on bone mineral density (BMD) in women with
      postmenopausal osteoporosis, a large multicentric European study was designed and
      is presently ongoing. Included in the study were 460 Caucasian, nonobese
      postmenopausal women aged > 45 and < 75 years, menopaused for at least 12 months.
      Inclusion was on the basis of a lumbar bone mineral density (BMD) lower than 2 SD
      compared with healthy women aged 50 years, corresponding to values below 0.860
      g/cm2 (antero-posterior measurement) by Hologic QDR 1000. Women with prevalent
      vertebral fractures were excluded as well as those presenting secondary
      osteoporosis or having been treated with medications that could affect bone
      metabolism. This study was designed as a 3-year, double-blind, placebo
      controlled, parallel group study that randomized the women to the oral
      administration of either 3 x 200 mg/day of i.p. or placebo. All patients received
      a daily supplement of 500 mg calcium. The primary purpose of the study was to
      evaluate the efficacy of i.p. in preventing vertebral nontraumatic fractures.
      Fracture is defined here as a > or = 20% decrease in any anterior, central, or
      posterior T4-L4 vertebral height. Blinded vertebral X-ray readings and vertebral
      morphometry have been centralized in an independent Center, with standardized
      evaluation of two experts. Power calculations have been based on the hypothesis
      that 21% of placebo-treated patients would fracture within 3 years and that
      treatment with i.p. would lead to a 50% reduction in the incidence of fracture.
      Statistical tests have been designed to have a power of 80%, with a type I error
      equal to 5%. Secondary endpoints were changes in vertebral, radial, and femoral
      BMD. Centralized controls on 100% BMD scans would ensure the good quality of BMD
      readings. This study should verify the hypothesis that i.p. significantly
      decreases the risk of vertebral fracture in postmenopausal, osteoporotic women.

PMID- 9263615
TI  - The future of ipriflavone in the management of osteoporotic syndromes.

PMID- 9263617
TI  - Effects of combined training loads on relations among force, velocity, and power
      development.
AB  - The effects of different training programs on the force-velocity relation and the
      maximum power output from the elbow flexor muscles were examined in 12 male
      adults. The subjects were divided into two equal groups (G30 + 100 and G30 + 0).
      In the G30 + 100 group, training was performed with five repetitions at 30%
      maximum strength (Fmax) and five isometric contractions (100% Fmax), and in the
      G30 + 0 group with five repetitions at 30% Fmax and five contractions with no
      load (0% Fmax). Training was performed 3 days a week for 11 weeks. Maximum power
      increased significantly in both groups after training. The power increase was
      significantly greater in the G30 + 100 group. Maximum strength was significantly
      higher only in the G30 + 100 group, while maximum velocity increased in both
      groups. No significant difference in strength or velocity gain was observed
      between the two groups. These results suggest that isometric training at maximum
      strength (100% Fmax) is a more effective form of supplementary training to
      increase power production than no load training at maximum velocity.

PMID- 9263616
TI  - Human skeletal muscle fiber types: delineation, development, and distribution.
AB  - This brief review attempts to summarize a number of studies on the delineation,
      development, and distribution of human skeletal muscle fiber types. A total of
      seven fiber types can be identified in human limb and trunk musculature based on
      the pH stability/lability of myofibrillar adenosine triphosphatase (mATPase). For
      most human muscles, mATPase-based fiber types correlate with the myosin heavy
      chain (MHC) content. Thus, each histochemically identified fiber has a specific
      MHC profile. Although this categorization is useful, it must be realized that
      muscle fibers are highly adaptable and that innumerable fiber type transients
      exist. Also, some muscles contain specific MHC isoforms and/or combinations that
      do not permit routine mATPase-based fiber typing. Although the major populations
      of fast and slow are, for the most part, established shortly after birth, subtle
      alterations take place throughout life. These changes appear to relate to
      alterations in activity and/or hormonal levels, and perhaps later in life, total
      fiber number. Because large variations in fiber type distribution can be found
      within a muscle and between individuals, interpretation of data gathered from
      human muscle is often difficult.

PMID- 9263618
TI  - One-mile run-walk performance in young men and women: role of anaerobic
      metabolism.
AB  - The aim of this study was to evaluate the importance of anaerobic metabolism as a
      determinant of individual differences in performance of a 1-mile run-walk (MRW).
      Anaerobic capacity, percentage of anaerobic capacity used during the MRW,
      percentage of energy used during the MRW that was supplied through anaerobic
      processes, aerobic metabolic determinants of distance running performance, and
      MRW time were measured in 26 male and 29 female young adult nonathletes.
      Anaerobic processes averaged 7-8% of the energy used during the MRW. In multiple
      regression analyses, anaerobic capacity, and a linear combination of all three
      anaerobic variables contributed significantly to the prediction of MRW with the
      effects of gender and VO2 peak held constant, but the additional variance
      accounted for by the anaerobic variables was relatively small (2-7%). In
      conclusion, anaerobic metabolism supplies only a small portion of the energy used
      during the MRW, and anaerobic capacity and metabolism during the MRW do not
      confound its interpretation as an indicator of maximal aerobic power in a
      heterogeneous group of young men and women of moderate fitness level.

PMID- 9263619
TI  - Hemodynamic strategies in blood pressure regulation during orthostatic challenge
      in women.
AB  - Several studies indicate that carotid baroreflex responsiveness is a good
      predictor of orthostatic tolerance. Two groups of healthy women with high (HI)
      and low (LO) carotid baroreflex responsiveness were studied (a) to determine any
      differences in the level of orthostatic tolerance of the two groups, and (b) to
      study the hemodynamic strategies used by HI and LO responders to regulate
      arterial pressure during the orthostatic challenge of lower body negative
      pressure (LBNP). Orthostatic tolerance was similar between the two groups,
      whereas the hemodynamic strategies recruited to maintain blood pressure at -40
      mmHg LBNP differed: HI responders exhibited greater LBNP-induced decreases in
      stroke volume and cardiac output, as well as a greater increase in peripheral
      resistance compared to LO responders (p < .05). In addition, a significant
      increase in plasma renin activity during LBNP was found in the HI responders
      only. No significant between-group differences were found in arterial and
      cardiopulmonary control of vascular resistance or arterial baroreflex control of
      heart rate during LBNP.

PMID- 9263620
TI  - Dynamics of the ventilatory response to step changes in end-tidal PCO2 in older
      humans.
AB  - The purpose of this study was to examine the ventilatory response to carbon
      dioxide (CO2) in young and older men. Six square-wave steps of end-tidal CO2
      (PETCO2) were administered in euoxia (PETO2 = 100 torr), hyperoxia (PETO2 = 500
      torr), and mild hypoxia (PETO2 = 60 torr). The peripheral and central chemoreflex
      loops were described by three parameters including a gain (gp and gc), time
      constant of the response (tau p, tau c), and a time delay (Tp, Tc), respectively.
      The young and older men showed similar characteristics for Tp and Tc, with Tp
      being 3 to 5 s shorter than Tc. In hypoxia, the ventilatory responses of the old
      group were characterised by a significantly smaller gc and a smaller gp. In
      hypoxia, tau c was significantly shortened from its euoxic value in the young
      group, but not in the old group. Thus, this study demonstrated that in older men,
      the ventilatory responses to CO2 in euoxia and hyperoxia are similar to younger
      men, while in hypoxia the ventilatory responses are characterised by smaller gain
      terms.

PMID- 9263621
TI  - Glycogen storage in fetuses of trained pregnant rats.
AB  - The purpose was to determine if running 30 m/min on a 10 degrees incline, 60
      min/day for 5 days/ week altered fetal glycogen storage in prepregnancy trained
      rats. Animals that exercised for 3 weeks prior to pregnancy either continued the
      same exercise program until Day 19 of gestation (pregnant running group [PR]), or
      ceased exercising at conception (pregnant controls [PC]). A separate set of
      animals did not exercise either before or during pregnancy (pregnant nonrunning
      control group [PNRC]). On Day 20 of gestation, fetal organs and placenta were
      weighted and analyzed for glycogen concentration. Glycogen concentrations were
      not different in either fetal liver, heart, or placenta of PR rats compared to
      PNRC animals. However, fetal liver glycogen concentration was significantly lower
      in the fetal heart and liver of PC animals compared to glycogen measured in both
      PNRC and PR animals (p < .05). These results suggest that exercise of this
      intensity does not compromise fetal glycogen storage in trained pregnant rats.
      However, chronic prepregnancy exercise and then abrupt cessation of exercise at
      conception may compromise fetal growth and development.

PMID- 9263622
TI  - Preservation of reproductive function before therapy for cancer: new options
      involving sperm and ovary cryopreservation.
AB  - In summary, sperm cryopreservation for future ICSI and ovarian tissue
      cryopreservation for future autotransplantation are new opportunities to preserve
      reproductive options of great importance to patients with newly diagnosed cancer.
      Since patients must utilize these strategies before cancer therapy is initiated,
      and these patients will not have a future chance to benefit once therapy has
      damaged gonadal function, awareness of these technologies among oncologists,
      radiation therapists, and other colleagues who interface with the victims of
      cancer is a high priority.

PMID- 9263623
TI  - Bicalutamide ('Casodex') development: from theory to therapy.

PMID- 9263624
TI  - 'Casodex': defining the role of antiandrogens.

PMID- 9263625
TI  - Time for a change.

PMID- 9263626
TI  - Histologic markers and long-term prognosis in breast cancer.

PMID- 9263627
TI  - Predictive factors for outcome in invasive bladder cancer treated with
      alternating chemoradiotherapy.
AB  - PURPOSE: In order to select patients properly for a bladder preservation program,
      this retrospective study aimed to evaluate the predictive role of pretreatment-
      and treatment-related factors in a group of patients with invasive bladder cancer
      treated with alternating chemoradiotherapy at a single institution. METHODS AND
      MATERIALS: From 1986 to 1994, 72 patients with invasive bladder cancer, stages T1
      poorly differentiated or T2-4M0 refusing surgery or not eligible for surgery,
      were treated with alternating chemoradiotherapy. Each patient had a pretreatment
      cystoscopy with an attempted complete transurethral resection of the bladder
      tumor (TURB). The treatment schedule consisted of chemotherapy (cisplatin, 5
      fluorouracil, or methotrexate) alternated with radiotherapy. Over the years, the
      treatment schedule was modified with respect to the total number of chemotherapy
      cycles, the type of chemotherapy drugs, the dose per fraction and total dose of
      radiation therapy, and the presence of a planned treatment gap at midtreatment.
      Treatments were aligned in order of their received average relative dose
      intensities of both chemotherapy (ARDICT) and radiotherapy (RDIRT). RESULTS:
      Twenty-two patients (76%) developed infiltrative bladder recurrences for an
      estimated 5-year pelvic control rate of 68% +/- 6%; 5-year actuarial survival
      with intact bladder is 40% +/- 6%. Obstructive uropathy at diagnosis, residual
      disease after TURB, and ARDICT value equal or below the median were independent
      predictive factors for pelvic failure, with hazard ratios of 2.87 (95% confidence
      interval [CI], 1.16-7.04), 8.13 (95% CI, 2.74-24.1), and 3.36 (95% CI, 1.29
      8.74), respectively. A more detailed model including interactions among these
      factors showed that the negative prognostic effect of obstructive uropathy at
      diagnosis was not modified by ARDICT or TURB resection; on the contrary, the risk
      of local failure for patients with incomplete TURB was markedly affected by
      different levels of ARDICT. Also, a trend toward a better local outcome was
      observed for patients with RDIRT above the median. Hydronephrosis and incomplete
      TURB were also independent predictors of distant metastases and overall survival,
      but no effect was found for ARDICT on these endpoints. DISCUSSION: As a result of
      this analysis we believe that (1) patients with obstructive uropathy should not
      be offered a bladder-sparing approach, (2) gross total TURB of the primary tumor
      should be maximized, (3) prompt surgery should be considered for patients with
      incomplete TURB who are not compliant with the combined-modality treatment, and
      (4) the intrinsic value of dose intensity of both chemotherapy and radiotherapy
      should be confirmed in a prospective, controlled study.

PMID- 9263628
TI  - Breast cancer metastatic phenotype as predicted by histologic tumor markers.
AB  - PURPOSE: Two clinical characteristics of the metastatic cancer phenotype are
      virulence-which reflects the pace of disease growth, clinical manifestation, and
      dissemination-and metastagenicity, the ultimate likelihood of distant metastasis.
      Molecular markers may allow distinguishing between these two cancer phenotypes.
      The purpose of this study is to determine whether proliferating cell nuclear
      antigen (PCNA) and tumor nuclear grade are markers of virulence or
      metastagenicity. PATIENTS AND METHODS: PCNA and tumor nuclear grade were
      determined in patients with extensive follow-up, treated only with mastectomy,
      for whom archival paraffin-embedded tissue was available. RESULTS: There is no
      significant difference in long-term disease-free survival (DFS) as a function of
      PCNA, but after only 5 years of analysis there are significant differences that
      gradually disappear with further follow-up, reflecting differences in virulence.
      While the likelihood of recurrence is the same, in patients with high PCNA 80% of
      disease recurrences become evident in the first 2 to 3 years, whereas in patients
      with low PCNA it takes more than 10 years for 80% of metastases to become
      clinically detectable. There was a significant difference in 20-year DFS for
      nuclear grade 1 compared with nuclear grade 2 and 3 tumors, indicating a
      difference in metastagenicity. The differences in DFS between nuclear grade 2 and
      3 tumors decrease as the length of follow-up increases; thus, like PCNA, these
      grade differences are also a marker of virulence. Eighty percent of the
      metastasis became evident within 4 years in grade 3 tumors and within 12 years in
      grade 2 tumors. DISCUSSION: PCNA and nuclear grade (2 vs 3) are markers of
      virulence. We have previously shown angiogenesis to be a marker of
      metastagenicity as is, in this study, the difference between nuclear grade 1 and
      nuclear grades 2 and 3. Both phenotypic characteristics, virulence and
      metastagenicity, are important to understanding the natural history of the tumors
      and may influence the nature of the therapy.

PMID- 9263629
TI  - Overexpression of BCL-x protein in primary breast cancer is associated with high
      tumor grade and nodal metastases.
AB  - PURPOSE: Dysregulation of genes that control apoptosis can contribute to tumor
      progression and increased drug resistance. The BCL2 gene and its family member
      BCL-x as well as the TP53 genes regulate apoptosis and have been shown to have a
      direct effect on the sensitivity of cancer cells to radiation and
      chemotherapeutic agents. METHODS: The expression of BCL-x, a BCL2-related protein
      that is a potent inhibitor of apoptosis, was investigated by immunohistochemical
      and immunoblot methods in 43 primary untreated breast carcinomas, in conjunction
      with BCL2 and TP53. RESULTS: BCL-x protein was overexpressed in 18 of 42 (43%)
      invasive breast cancers when compared with adjacent normal breast epithelium.
      Western blot analysis of eight primary breast cancers and five breast cancer cell
      lines indicated that BCL-xL was the predominant BCL-x protein expressed.
      Overexpression of BCL-x protein in these tumors was associated with higher tumor
      grade and increased number of positive nodes. In contrast, BCL2 protein was
      overexpressed in 19 of 42 tumors (45%) and was strongly correlated with estrogen
      receptor positivity, lower tumor grade, smaller tumor size, and lower stage. TP53
      protein immunostaining was detected in 12 of 40 tumors (29%) and was inversely
      correlated with BCL2 expression and ER positivity. There was no correlation
      between the level of BCL-x protein expression and age, tumor size, ER status, and
      TP53 status. At a median follow-up time of 216 weeks, there was a trend toward
      decreased overall survival in patients with tumors overexpressing BCL-x.
      CONCLUSIONS: These findings suggest that expression of BCL-x protein is increased
      in a significant fraction of invasive breast cancers. In contrast to BCL2
      expression, up-regulation of BCL-x protein may be a marker of tumor progression.
      Additional data including larger numbers of patients, more uniform treatments,
      and longer follow-up are needed to define the prognostic significance of
      overexpression of BCL-x during breast cancer progression.

PMID- 9263630
TI  - Adult medulloblastoma: an analysis of survival and prognostic factors.
AB  - PURPOSE: This analysis aimed to review the experience in the management of adult
      medulloblastoma at the University of California, San Francisco, and to identify
      important prognostic factors for survival and posterior fossa control. PATIENTS
      AND METHODS: We performed a retrospective review of 34 adult patients, age > or =
      15, with cerebellar medulloblastoma treated with radiotherapy at the University
      of California, San Francisco from 1970 to 1994. All patients underwent a surgical
      procedure (complete resection in 17, subtotal resection in 10, and biopsy alone
      in seven), followed by craniospinal irradiation. Most patients treated after 1979
      also received chemotherapy. Twenty were classified as poor-risk due to either
      incomplete resection or evidence of disease outside of the posterior fossa at
      diagnosis. RESULTS: The 5-year posterior fossa control and overall survival rates
      were 61% and 58%, respectively. The majority of relapses occurred in the
      posterior fossa (14 of 17). Multivariate analysis revealed that age (favoring
      older patients), gender (favoring female patients), and extent of disease at
      diagnosis (favoring localized disease) were important prognostic factors for
      posterior fossa control. There was a trend toward improved posterior fossa
      control with higher radiation dose to the posterior fossa in patients with a
      complete resection. Gender and extent of disease at presentation were significant
      prognostic factors for survival. The 5-year survival rates were 92% for female
      patients versus 40% for male patients, and 67% for patients with localized
      disease versus 25% for those with disseminated disease. The prognosis following
      recurrence was poor; all died of the disease. DISCUSSION: Survival for adult
      medulloblastoma was comparable to its pediatric counterpart. In patients with
      localized disease at presentation, gender (favoring female patients) and age
      (favoring older patients) were important prognostic factors for posterior fossa
      control and survival. In patients with disseminated disease at presentation, the
      prognosis is poor, and innovative therapy is needed to improve survival.

PMID- 9263631
TI  - Carboplatin and short-infusion paclitaxel in high-risk and advanced-stage ovarian
      carcinoma.
AB  - PURPOSE: To present tolerance and toxicity information on previously untreated
      high-risk early-stage and advanced-stage primary epithelial ovarian cancer
      patients treated with adjuvant 3-hour paclitaxel and carboplatin. PATIENTS AND
      METHODS: Consecutive patients with high-risk early-stage and advanced-stage
      epithelial ovarian cancer underwent maximal surgical debulking and/or staging.
      Paclitaxel (175 mg/m2) was infused over 3 hours followed by a 30-minute
      carboplatin infusion (area under the plasma concentration time curve = 7.0-7.5
      mg/mL/min) for a planned six (q 21 day) courses. RESULTS: Twenty-two patients
      underwent 132 cycles and were evaluable for toxicity. Myelosuppression was dose
      limiting. Grade 4 granulocytopenia occurred in 31% of the cycles. Grade 3 and 4
      thrombocytopenia was uncommon (5%, 1%) and predictable. Delay in administration
      was necessary in 10 of 132 (7.6%) cycles (5 of 22 patients). Eight of these 10
      delays were 7 days. Seventeen of 22 (77%) patients completed therapy without a
      delay. Non-hematologic toxicity was mild. A significant individual weight gain of
      2.5 kg was noted. Among 19 patients with advanced disease, 16 had a complete
      clinical remission after six cycles of therapy. Nine patients with stage IIB-IV
      disease have undergone reassessment procedures (four pathologic complete
      responses, three microscopic positive, two macroscopic positive). Sixteen of 22
      (77%) have no evidence of disease, four have no evidence of disease following a
      secondary therapy, one is under therapy with salvage chemotherapy, and one is
      dead of disease. Median follow-up is 14 months (range: 6-30 months).
      Comparatively, the mean carboplatin dose administered was 440 mg/m2 (95% CI, 428
      486 mg/m2). CONCLUSION: Paclitaxel and carboplatin administered in this design
      are well tolerated, with predictable and acceptable hematologic and
      nonhematologic toxicity. Dose-limiting toxicity is granulocytopenia with relative
      platelet sparing. Outpatient administration is safe.

PMID- 9263632
TI  - Genetic predisposition testing for breast cancer.

PMID- 9263633
TI  - Comparison of prostate cancer treatments.

PMID- 9263634
TI  - Killing two birds with one stone: a chemically plausible scheme for linked
      nucleic acid replication and coded peptide synthesis.
AB  - To understand how life began, we must explain the origins of nucleic acid
      replication and genetically coded peptide synthesis. Neither of these is easy to
      explain individually; here, we propose a chemically plausible scheme for the
      evolution of a process that simultaneously produced both polymers. Later, two
      separate machineries could have evolved from the linked process.

PMID- 9263635
TI  - The road less travelled: taming phosphatases.
AB  - Phosphatases are important in signal transduction, bacterial pathogenesis and
      several human diseases. So far, however, it is their opposite numbers, the
      kinases, that have received more attention from chemists. Recent progress in
      inhibitor development offers hope that new probes of cellular processes, and
      perhaps novel therapeutic agents, may soon become available.

PMID- 9263636
TI  - How to starve a tumor.
AB  - The formation of new blood vessels, termed angiogenesis, is a central process in
      the evolution of a tumor and its subsequent metastasis. Angiogenesis is potently
      inhibited by the fumagillins, a family of epoxide-containing natural products.
      The recent identification of a protein target for these compounds may help
      decipher the mechanisms underlying endothelial cell growth. The fact that binding
      is irreversible may inspire the design of electrophilic inhibitors of other,
      poorly understood cellular processes.

PMID- 9263638
TI  - A limitation of two-state analysis for transitions between disordered and weakly
      ordered states.
AB  - BACKGROUND: The stability of the secondary structure of particular peptide
      regions is often used to investigate the involvement of the region in protein
      folding. When analysing the relatively small populations of associated states
      that are formed by weak interactions (i.e. those interactions that are comparable
      to thermal energies), it is common practice to characterise the associated state
      by a parameter that is measured when this state is highly occupied. The accuracy
      of this method, however, has not yet been determined. RESULTS: Using as a model
      the vancomycin group of antibiotics, either forming dimers or binding to cell
      wall precursors, we have investigated the dependence of the limiting (i.e. fully
      associated) chemical shifts of two protons on the equilibrium constants for the
      formation of the fully associated states. The chemical shift shows a large
      variation with the equilibrium constant for the formation of the fully associated
      state. CONCLUSIONS: The results demonstrate, in two systems, that a parameter
      representing a fully associated state (chemical shift) varies greatly with the
      equilibrium constant for the formation of that associated state. The results have
      implications for two-state analyses of populations of protein fragments in which
      a parameter representing the fully associated state is taken to be independent of
      the equilibrium constant for its formation. Using two-state analysis to determine
      the population of associated states of protein fragments could result in an
      underestimation of the population of these associated states.

PMID- 9263637
TI  - Designed protein pores as components for biosensors.
AB  - BACKGROUND: There is a pressing need for new sensors that can detect a variety of
      analytes, ranging from simple ions to complex compounds and even microorganisms.
      The devices should offer sensitivity, speed, reversibility and selectivity. Given
      these criteria, protein pores, remodeled so that their transmembrane conductances
      are modulated by the association of specific analytes, are excellent prospects as
      components of biosensors. RESULTS: Structure-based design and a separation method
      that employs targeted chemical modification have been used to obtain a
      heteromeric form of the bacterial pore-forming protein staphylococcal alpha
      hemolysin, in which one of the seven subunits contains a binding site for a
      divalent metal ion, M(II), which serves as a prototypic analyte. The single
      channel current of the heteromer in planar bilayers is modulated by nanomolar
      Zn(II). Other M(II)s modulate the current and produce characteristic signatures.
      In addition, heteromers containing more than one mutant subunit exhibit distinct
      responses to M(II)s Hence, a large collection of responsive pores can be
      generated through subunit diversity and combinatorial assembly. CONCLUSIONS:
      Engineered pores have several advantages as potential sensor elements:
      sensitivity is in the nanomolar range; analyte binding is rapid (diffusion
      limited in some cases) and reversible; strictly selective binding is not required
      because single-channel recordings are rich in information; and for a particular
      analyte, the dissociation rate constant, the extent of channel block and the
      voltage-dependence of these parameters are distinguishing, while the frequency of
      partial channel block reflects the analyte concentration. A single sensor element
      might, therefore, be used to quantitate more than one analyte at once. The
      approach described here can be generalized for additional analytes.

PMID- 9263639
TI  - A unique mechanism for RNA catalysis: the role of metal cofactors in hairpin
      ribozyme cleavage.
AB  - BACKGROUND: Ribozymes are biological catalysts that promote the hydrolysis and
      transesterification of phosphate diesters of RNA. They typically require divalent
      magnesium ions for activation, although it has proven difficult to differentiate
      structural from catalytic roles for the magnesium ions and to identify the
      molecular mechanism of catalysis. Direct inner-sphere coordination is usually
      invoked in the catalytic step, although there is no evidence to support the
      generality of such a pathway for all ribozymes. RESULTS: We studied the catalytic
      pathway for the hairpin class of ribozyme. The substitutionally inert transition
      metal complex cobalt hexaammine [Co(NH3)6(3+)] was shown to be as active as
      Mg2+(aq) in promoting hairpin ribozyme activity, demonstrating that inner-sphere
      pathways are not used by this class of ribozyme. These results were confirmed by
      studies with Rp- and Sp-phosphorothioate substrate analogs which show a similar
      reactivity to that of the native substrate towards the magnesium-activated
      ribozyme. Monovalent cations enhance the activity of Co(NH3)6(3+)-promoted
      reactions, but inhibit Mg(2+)-activated catalysis, demonstrating a requirement
      for hydrated cations at several key sites in the ribozyme. CONCLUSIONS: These
      results provide clear support for a model of RNA catalysis that does not involve
      direct coordination of magnesium to the phosphate ester, nor activation of a
      bound water molecule. A mechanism in which catalysis is carried out by functional
      groups on the RNA ribozyme itself is possible; such functional groups are likely
      to have pKa values that are appropriate for carrying out this catalysis. The
      metal cofactor would then serve to define the architecture of the catalytic
      pocket and contribute to the stabilization of transient species, as has been
      described earlier. Hydrolytic pathways in nucleic acid reactions are apparently
      more diverse than was previously thought, and the hairpin ribozyme falls into a
      mechanistically distinct class from the Tetrahymena and the hammerhead ribozymes.

PMID- 9263640
TI  - Stretching and breaking duplex DNA by chemical force microscopy.
AB  - BACKGROUND: Specific interactions between complementary strands of DNA and other
      molecules are central to the storage, retrieval and modification of information
      in biological systems. Although in many cases the basic structures of duplex DNA
      and the binding energetics have been well characterized, little information is
      available about the forces in these systems. These forces are of critical
      importance because they must be overcome, for example, by protein machines during
      transcription and repair. Recent developments in atomic force microscopy make
      possible direct measurements of such forces between the individual
      oligonucleotide strands that form DNA duplexes. RESULTS: We used the chemical
      force microscopy technique, in which oligonucleotides are covalently linked to
      the force microscope probe tip and the sample surface, to measure the elongation
      and binding forces of individual DNA duplexes. The separation forces between
      complementary oligonucleotide strands were found to be significantly larger than
      the forces measured between noncomplementary strands, and to be consistent with
      the unbinding of a single DNA duplex. With increasing applied force, the
      separation of complementary strands proceeded in a stepwise manner: B-form DNA
      was stretched, then structurally transformed to a stable form of DNA
      approximately twice the length of the B form, and finally separated into single
      stranded oligonucleotides. These data provide a direct measurement of the forces
      required to elastically deform and separate double-stranded DNA into single
      strands. CONCLUSIONS: Force microscopy provides a direct and quantitative
      measurement of the forces and energetics required to stretch and unbind DNA
      duplexes. Because the measurements can be carried out readily on synthetic
      oligonucleotides and in the presence of exogenous molecules, this method affords
      an opportunity for directly assessing the energetics of distorting and unbinding
      specific DNA sequences and DNA complexes. Such data could provide unique insights
      into the mechanistic steps following sequence-specific recognition by, for
      example, DNA repair and transcription factors.

PMID- 9263641
TI  - Glucosylation of the peptide leucinostatin A, produced by an endophytic fungus of
      European yew, may protect the host from leucinostatin toxicity.
AB  - BACKGROUND: Yew species (Taxus spp.) throughout the world are hosts to hundreds,
      or perhaps thousands, of endophytic organisms. Most commonly, these organisms are
      fungi, living in a commensal or a symbiotic relationship with their host plant,
      so the plants exhibit little or no outward evidence that they are supporting
      these microorganisms. Little is known about any of the biochemical mechanisms
      that mediate the interactions between the yew host and its associated microbes.
      We feel that such information may not only contribute to our understanding of
      endophyte-tree biology, but also may provide novel pharmaceutical leads, because
      some of the compounds produced by these endophytes have demonstrated
      pharmacological activities. RESULTS: Acremonium sp. was isolated as an endophytic
      fungus of the European yew, Taxus baccata. Entry of Acremonium sp. into the plant
      may proceed via invasion of natural openings such as stomata. The relationship
      between Acremonium sp. and T. baccata may be a symbiotic one, because no symptoms
      are seen when Taxus media p.v. Hicksii is inoculated with this fungus. In
      culture, the fungus makes leucinostatin A, a peptide with phytotoxic, anticancer
      and antifungal properties. Although this peptide causes necrotic symptoms in many
      non-host plants and other cell types, it causes no visible symptoms in the host
      plant. T. baccata and several other plants have a UDP glucose; leucinostatin A
      glucosyl transferase that catalyzes the production of leucinostatin A beta di-O
      glucoside from leucinostatin A. This glucoside, also made by the fungus, has a
      lower bioactivity against plants, fungi and a breast cancer cell line, BT-20,
      than leucinostatin A. CONCLUSIONS: Leucinostatin A may be one of several
      potentially toxic peptides produced by Acremonium sp. that contribute to the
      defense of the host, thereby preserving the fungus' own biological niche. The
      host plant is relatively immune to leucinostatin A because it has an enzyme which
      transfers two glycosyl residues to leucinostatin A, markedly reducing the
      peptide's bioactivity. Our results suggest that glucosylation reactions may play
      a more general role in plant defenses, especially against toxin-mediated disease
      development.

PMID- 9263642
TI  - Shine a light, Aurora Biosciences Corporation.

PMID- 9263643
TI  - The molecular epidemiology of lung cancer.
AB  - One in ten tobacco smokers develops bronchogenic carcinoma over a lifetime. The
      study of susceptibility of an individual and a population to lung cancer
      traditionally has been limited to the study of tobacco smoke dose and family
      history of cancer. New insights into lung carcinogenesis have made the study of
      molecular markers of risk possible in human populations in the emerging field of
      molecular epidemiology. This review summarizes data addressing the relationships
      of human lung cancer to polymorphisms of phase I procarcinogen-activating and
      phase II-deactivating enzymes and intermediate biomarkers of DNA mutation, such
      as DNA adducts, oncogene and tumor suppressor gene mutation, and polymorphisms.
      These parameters are reviewed as they relate to tobacco smoke exposure,
      procarcinogen metabolizing polymorphisms, and the presence of lung cancer.
      Problem areas in biomarker validation, such as cross-sectional data
      interpretation; tissue source, race, statistical power, and ethical implications
      are addressed.

PMID- 9263644
TI  - Methoxychlor as a model for environmental estrogens.
AB  - Estrogens can have a variety of physiological effects, especially on the
      reproductive system. Chemicals with estrogenic activity that are present in the
      environment may thus be considered potentially hazardous to development and/or
      reproduction. Methoxychlor is one such chemical, a chlorinated hydrocarbon
      pesticide with proestrogenic activity. Metabolism of the chemical either in vivo
      or using liver microsomes produces 2,2-bis(p-hydroxyphenyl)- 1,1,1
      trichloroethane (HPTE), the active estrogenic form, and the delineation of this
      mechanism is reviewed herein. When administered in vivo, methoxychlor has adverse
      effects on fertility, early pregnancy, and in utero development in females as
      well as adverse effects on adult males such as altered social behavior following
      prenatal exposure to methoxychlor. Effects of methoxychlor on the female have
      been studied extensively, whereas reports on the chemical's effects on males are
      less common. From the studies reviewed here, the reproductive toxicity of
      methoxychlor is evident, but the significance of this toxicity with respect to
      human health remains to be determined.

PMID- 9263645
TI  - Differential effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin, bis(tri-n-butyltin)
      oxide and cyclosporine on thymus histophysiology.
AB  - Recent advances in the histophysiology of the normal thymus have revealed its
      complex architecture, showing distinct microenvironments at the light and
      electron microscopic level. The epithelium comprising the major component of the
      thymic stroma is not only involved in the positive selection of thymocytes, but
      also in their negative selection. Dendritic cells, however, are more efficient
      than epithelial cells in mediating negative selection. Thymocytes are dependent
      on the epithelium for normal development. Conversely, epithelial cells need the
      presence of thymocytes to maintain their integrity. The thymus rapidly responds
      to immunotoxic injury. Both the thymocytes and the nonlymphoid compartment of the
      organ can be targets of exposure. Disturbance of positive and negative thymocyte
      selection may have a major impact on the immunological function of the thymus.
      Suppression of peripheral T-cell-dependent immunity as a consequence of thymus
      toxicity is primarily seen after perinatal exposure when the thymus is most
      active. Autoimmunity may be another manifestation of chemically mediated thymus
      toxicity. Although the regenerative capacity of thymus structure is remarkable,
      it remains to be clarified whether this also applies to thymus function. In-depth
      mechanistic studies on chemical-induced dysfunction of the thymus have been
      conducted with the environmental contaminants 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) and bis(tri-n-butyltin)oxide (TBTO) as well as the pharmaceutical
      immunosuppressant cyclosporine (CsA). Each of these compounds exerts a
      differential effect on the morphology of the thymus, depending on the cellular
      targets for toxicity. TCDD and TBTO exposure results in cortical lymphodepletion,
      albeit by different mechanisms. An important feature of TCDD-mediated thymus
      toxicity is the disruption of epithelial cells in the cortex. TBTO primarily
      induces cortical thymocyte cell death. In contrast CsA administration results in
      major alterations in the medulla, the cortex remaining largely intact. Medullary
      epithelial cells and dendritic cells are particularly sensitive to CsA. The
      differential effects of these three immunotoxicants suggest unique
      susceptibilities of the various cell types and regions that make up the thymus.

PMID- 9263646
TI  - Update on local cardiac renin-angiotensin system.
AB  - In the past decade evidence has accumulated for local tissue renin-angiotensin
      systems and for direct trophic effects of angiotensin II. In the present update
      we review new evidence for the independent generation of cardiac angiotensin II
      and its relevance for cardiac pathophysiology. A major role of angiotensin II
      generated by cardiac tissue has become apparent for the development of volume
      overload-induced cardiac hypertrophy. In contrast, evidence that cardiac pressure
      overload is associated with increased generation of angiotensin II by cardiac
      tissue is missing, and a role for angiotensin II produced by cardiac tissue in
      pressure overload-induced cardiac hypertrophy remains to be addressed. Similarly,
      although evidence has accumulated for increased gene expression and production of
      components of the renin-angiotensin system in the area adjacent to a myocardial
      infarction, data on changes in cardiac angiotensin II in infarcted or remnant
      myocardium are very limited. Without these, one can not assess whether blockade
      of angiotensin II generated by cardiac tissue contributes to the beneficial
      effects of blockers of the renin-angiotensin system on cardiac remodeling
      postmyocardial infarction.

PMID- 9263647
TI  - Clinical significance of endothelin in cardiovascular disease.
AB  - Endothelins are ubiquitously produced 21-amino-acid peptides that were discovered
      as an endothelial product and may play important roles in cardiovescular
      physiology and pathophysiology. The main endothelin produced by the endothelium
      is endothelin-1. The vasoconstrictor role of endothelins may participate in blood
      pressure elevation and vascular hypertrophy in salt-dependent models of
      hypertension (deoxycorticosterone acetate-salt hypertensive rats, spontaneously
      hypertensive rats treated with deoxycorticosterone, acetate and salt, and Dehl
      salt-sensitive rats), and in stroke-prone spontaneously hypertensive rats. In
      humans, endothelins may play important roles in moderate to severe essential
      hypertension, and in the hypertension of African-Americans. Endothelins may be
      involved in cardiac hypertrophy, and there is increasing evidence of their
      participation in heart failure, in which acute endothelin antagonism in humans
      exerts beneficial effects. Endothelin expression is enhanced in smooth muscle
      cells migrating into the intima of arteries in atherosclerosis, suggesting a role
      in atherogenesis. Endothelin may participate as a vasoconstrictor in coronary
      artery disease, and as a contributor to intimal proliferation in restenosis after
      coronary angioplasty. In patients with myocardial infarction, cardiac production
      of endothelin is increased, particularly in those with cardiogenic shock. There
      is a potential for participation of endothelins in vasospasm accompanying stroke
      or subarachnoid hemorrhage: in the latter, endothelin antagonism has shown
      beneficial effects in experimental models. In neonatal and in primary pulmonary
      hypertension, endothelin expression is enhanced, and in experimental models
      endothelin antagonism resulted in favorable responses. Systemic sclerosis is
      another, peripheral, form of vascular disease in which endothelin may play a role
      and in which endothelin antagonism may be an interesting therapeutic alternative.
      The pathophysiologic role of endothelins is becoming increasingly apparent in
      cardiovascular disease, generating interesting potential therapeutic targets for
      the use of endothelin antagonists or endothelin-converting enzyme inhibitors.

PMID- 9263648
TI  - Rationale and benefits of classification of hypertension severity.
AB  - Classification schemes for hypertension are helpful in defining the condition,
      quantitating risk, estimating prognosis, and guiding management. Most "classic"
      systems classify hypertension based on the blood pressure level, according to
      "relative risk" (the proportional likelihood of cardiovascular events occurring
      as blood pressure--either systolic, diastolic, or both--rises). Several recent
      systems are based on "absolute risk," and quantify the risk for adverse events
      related to other cardiovascular risk factors besides hypertension. Classification
      schemes based on the pattern of blood pressure elevation, extent of damage to
      target organs from hypertension, and laboratory evaluations have also been
      suggested, but are, of necessity, more complicated than systems based simply on
      the blood pressure readings. Two novel systems of classifying hypertension have
      recently been proposed, incorporating most of the desirable attributes of the
      simpler (and widely used) methods of "staging" blood pressure, but adding a
      subscript to indicate the presence ("c") or absence ("u") of complications or
      other risk factors present in a given patient. This system also uses a subscript
      "e" to indicate the presence of a widened pulse pressure (more common in the
      elderly); such patients are more likely to benefit from hypertension treatment. A
      complete medical history and physical examination and a few inexpensive
      laboratory tests provide essentially all the information needed to classify an
      individual as "complicated" or "uncomplicated." This system also provides a guide
      to treatment, because drug therapy should be used sooner in those with
      complicated hypertension. Implementation of this system is likely to be enhanced
      if compensation for health care providers were higher when treating the higher
      stages of hypertension, especially an elderly patient with complicated
      hypertension, compared with a younger person with uncomplicated hypertension.

PMID- 9263649
TI  - Mechanisms of hypertension in cardiac transplantation and the role of
      cyclosporine.
AB  - The use of cyclosporine in solid organ transplantation has been shown to be
      associated with the development of hypertension and nephrotoxicity. Several
      mechanisms, including endothelin-mediated systemic vasoconstriction, impaired
      vasodilatation secondary to reduction in nitric oxide, and altered cytosolic
      calcium translocation, have been proposed to underlie cyclosporine-induced
      hypertension. In addition, other studies have shown activation of the sympathetic
      nervous system and the renin-angiotensin system, as well as abnormalities in
      prostaglandin metabolism, as culpable mechanisms. Hemodynamic features of
      cyclosporine-induced hypertension consist of elevated peripheral vascular
      resistance, ventricular vascular uncoupling contributing to left ventricular
      hypertrophy, and abnormalities in the diastolic function of the allograft.
      Combined calcium-channel blockers and angiotensin-converting enzyme inhibitors
      have been used for this treatment of this clinical problem, and they achieve
      blood pressure control in 65% of patients. Moreover, these agents may also be
      beneficial in preventing development of cardiac allograft vasculopathy, a long
      term nemesis in cardiac transplantation.

PMID- 9263650
TI  - New or developing antihypertensive agents.
AB  - Although significant pharmacologic and nonpharmacologic advances in treating
      hypertension during the last decade have reduced mortality and morbidity,
      hypertension continues to be a major health concern worldwide. Therefore, the
      search continues for newer specific pharmacologic treatment of this disorder.
      This review focuses on pharmacologic agents or classes of agents either recently
      approved or under clinical development for the treatment of hypertension.

PMID- 9263651
TI  - Aortic dissection.

PMID- 9263652
TI  - Aortic valve-sparing operations in patients with ascending aortic aneurysms.
AB  - Composite replacement of the aortic valve and ascending aorta was the standard
      treatment for patients with aortic insufficiency and aortic root aneurysm.
      However, it has been pointed out that the aortic valve leaflets are normal or
      near normal in almost one half of the patients who undergo surgery for aortic
      root aneurysms. It is now possible to accurately determine the quality of the
      aortic valve leaflets using transesophageal multiplane echocardiography, and with
      current knowledge of the functional anatomy of the aortic root, it is feasible to
      reconstruct the aortic root and preserve the aortic valve leaflets in these
      patients. There are various aortic valve-sparing procedures depending on the
      mechanism of aortic insufficiency and the pathology of the aortic root. Although
      these operations are now performed in many cardiac centers, long-term results are
      not yet available. Aortic valve-sparing operations have been performed in 97
      patients in our institution since 1988; the clinical results have been excellent
      and the valve repair remains stable for up to 8 years of follow-up. These results
      justify the continued use of these operative procedures.

PMID- 9263653
TI  - Endovascular stent graft repair of aortic aneurysms.
AB  - Vascular surgeons are increasingly encountering older patients with large
      aneurysms associated with severe comorbid conditions. This situation can increase
      operative morbidity and elevate the mortality rate of aortic surgery over 60%.
      With some frequency many patients will represent a prohibitive risk for
      conventional graft replacement. The endoluminal treatment of 110 patients has
      proved to be feasible and may represent an alternative solution. One hundred six
      of the patients had an abdominal aortic aneurysm and in four patients, the
      thoracic aorta was involved. All of them underwent endoluminal repair for the
      aortic pathology using the combination of stents and grafts in aorto-aortic or
      aorto-iliac position, with straight, tapered, or bifurcated stent-graft devices.
      The results are as follows: Initial success was 84% in aorto-aortic abdominal
      devices and 100% in aorto-aortic thoracic devices. In aorto-iliac devices,
      initial success was 75%. Late success rates were 62% of the initial group and 80%
      of the initially successful group.

PMID- 9263654
TI  - Clinical trials with implications regarding heart failure therapy.
AB  - Paradigms for the treatment of heart failure have changed substantially over the
      past several decades. It has been the performance of relatively large, carefully
      controlled and often mortality endpoint trials that has given us great insight
      into therapies that are advantageous, disadvantageous, or neutral with respect to
      outcomes in patients with heart failure. No longer is the care of a patient with
      ventricular dysfunction and heart failure solely rooted in the prescription of a
      diuretic and digoxin. Indeed, we have seen a rather radical evolution from this
      prescription practice to approaches that were thought to be contraindicated at
      one time, such as beta blocker and vasodilator therapy. Indeed, treatment
      paradigms today are shifting rapidly toward more complete attenuation of
      adrenergic processes known to be detrimental in this setting. It is important to
      review the recent clinical trials that have given us further insight into
      managing heart failure. Twenty trials published since 1995 have been selected
      because of the important insight they give us regarding the wide spectrum of
      therapeutic options available for individuals with heart failure.

PMID- 9263655
TI  - An update on acute myocardial infarction from recent clinical trials.
AB  - Exploration of new strategies and therapies to improve survival and outcomes of
      acute myocardial infarction (AMI) continues. Recently published large clinical
      trials, including the long-term results from Grampian Region Early Anistreplase
      Trial, Global Use of Strategies to Open Occluded Coronary Arteries, and the
      Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes
      (GUSTO-)IIb angioplasty substudy, have helped to clarify the relative benefits of
      earlier treatment, the use of third-generation thrombolytic agents, and the use
      of primary angioplasty. Other, smaller trials such as Evaluation of c7E3 Fab in
      Preventing ischemic Complications of High-risk Angioplasty and intracoronary
      Stenting and Antithrombotic Regimen have stimulated thoughts about new adjunctive
      agents and devices, including platelet glycoprotein IIb/IIIa antagonists, primary
      stenting, and antioxidants. Both knowledge and therapies have advanced
      significantly in the past year, which should improve clinical outcomes of AMI in
      the near future.

PMID- 9263656
TI  - Antiplatelet and antithrombin therapies in the acute coronary syndromes.
AB  - The circulating platelet and the soluble coagulation protein thrombin play key
      roles in the thrombosis responsible for the acute coronary syndromes. The
      standard antiplatelet and antithrombin agents used today in patients with acute
      coronary syndromes are aspirin and heparin. Despite our experience with these
      agents, they both have significant limitations. A number of new antiplatelet
      drugs, including clopidogrel and the glycoprotein IIb/IIIa antagonists, have been
      investigated in recent large clinical trials and show significant promise both in
      patients undergoing angioplasty and those with acute coronary syndromes. The
      results of recent trials with new antithrombin agents have been less impressive.
      Low-molecular-weight heparins appear to be beneficial in patients with acute
      coronary syndromes. Recent trials with direct thrombin inhibitors in patients
      with acute coronary syndromes have demonstrated modest benefit, but also revealed
      their narrow therapeutic window and associated risk of bleeding. Further trials
      with novel antiplatelet and antithrombin agents in patients with acute coronary
      syndromes are ongoing.

PMID- 9263657
TI  - Molecular biology of iron and zinc uptake in eukaryotes.
AB  - Recent studies of iron uptake in Saccharomyces cerevisiae have provided insights
      into the role of multicopper oxidases in eukaryotic metal transport. These
      studies have also led to the identification of a novel iron transporter in plants
      and the recognition of a new family of transporter proteins that may participate
      in metal uptake in a diverse array of eukaryotic species.

PMID- 9263658
TI  - Membranes and sorting.

PMID- 9263659
TI  - Membrane permeability.

PMID- 9263661
TI  - Epidemiology and prevention.

PMID- 9263660
TI  - Atherogenic lipoproteins and human disease: extending concepts beyond the heart
      to the kidney.

PMID- 9263662
TI  - Genetic factors in human hypertension.
AB  - The advancement of molecular biomedical techniques has allowed solutions to the
      problem of finding a genetic linkage to hypertension. This is now being
      approached by limiting study to a select number of genetic factors possibly
      influencing a particular physiologic dysfunction or structural defect. Analysis
      of chromosomal abnormalities or regions bearing a particular mutation have been
      greatly influenced by the ability to produce artificial chromosomes or to
      identify closely linked markers. Rapid accumulation of knowledge of the genetic
      map has led to a number of these gene/disease linkages. Perhaps the unraveling of
      some of the polygenic influences in hypertension may lead to even better
      treatment protocols to minimize the disease complications of elevated blood
      pressure.

PMID- 9263663
TI  - Metabolic abnormalities in hypertension.
AB  - Hypertension is often accompanied by a host of metabolic defects. Investigations
      have shown an association between insulin resistance, hyperinsulinemia,
      central/visceral obesity, and hypertension. Recent interest has focused on the
      fact that untreated hypertensive individuals have compensatory hyperinsulinemia,
      are resistant to insulin-mediated glucose uptake, and frequently have coexisting
      lipid abnormalities. Data from prospective studies appear to indicate that
      fasting hyperinsulinemia is an independent predictor of coronary artery disease.
      Additionally, there is evidence that hyperinsulinemia and diabetes eliminate the
      normal sex differences in the prevalence of coronary artery disease. The salutary
      effects of ovarian hormones on the prevalence of hypertension and cardiovascular
      disease in postmenopausal women are well established. Hyperandrogenism, in
      particular elevated serum levels of dehydroepiandrosterone sulfate, is believed
      to be a risk factor promoting sex-specific impairments of glucose and lipid
      metabolism, obesity, and hypertension in women. Clinical and epidemiologic
      evidence have linked elevated blood pressure to disturbances in lipoprotein
      metabolism, fibrinolytic activity, plasminogen activation inhibitor levels, and
      dyslipidemia. This review briefly presents the current understanding of various
      metabolic disturbances associated with hypertension, the pathophysiologic
      mechanisms involved, and the significance of the interplay between them relative
      to the complications of this disease.

PMID- 9263664
TI  - The emergence of case-control studies in hypertension research: valid or
      misleading?
AB  - Recently published case-control studies have generated considerable controversy.
      Compared with prospective studies, case-control studies permit investigation of
      uncommon diseases or outcomes in a more cost and time efficient manner. In
      addition, multiple possible risk factors can be studied simultaneously. If the
      assumptions of the study design are met, results of case-control studies are
      valid. For this reason, the use of this study design has increased markedly. This
      review summarizes the advantages and disadvantages of this study design and
      criteria to evaluate the results of such studies.

PMID- 9263665
TI  - The explosion of morbidity and mortality trials in hypertension.
AB  - The highlights of each generation of hypertension trials have been varied, but
      interrelated. The initial hypertension trials focused on middle-aged hypertensive
      individuals and later on the elderly, with emphasis on diastolic blood pressure
      and subsequently on systolic blood pressure. Past generations of trials
      elucidated whether and whom to treat. The current explosion of morbidity and
      mortality trials in hypertension largely seeks to learn what drugs should be used
      and to delineate what blood pressure goals should be targeted.

PMID- 9263666
TI  - Treatment of renal failure and blood pressure.
AB  - Some of the more important advances in slowing progression of renal disease in
      the past few years include the following: the identification of specific racial
      groups, such as African-Americans and Mexican-Americans, who are at higher risk
      for renal disease progression than the general population; the observation that
      African-Americans may require lower levels of blood pressure reductions (i.e. <
      125/75 mmHg) than the general population in order to achieve a similar degree of
      protection against renal disease progression; the understanding that angiotensin
      converting enzyme inhibitors in the early stages of diabetic renal disease and
      nondihydropyridine calcium-channel blockers in those with established renal
      insufficiency from diabetes slow renal disease progression and reduce
      proteinuria; and lastly, aggressive blood pressure reduction in dialysis patients
      is associated with a reduction in cardiovascular events.

PMID- 9263667
TI  - Further trends in the etiology of end-stage renal disease in African-Americans.
AB  - Publications in the past year have continued to shed light on the etiology of the
      excess risk of end-stage renal disease end-stage renal disease among African
      Americans. Prospective data now show that even mild elevations in blood pressure
      are associated with an increased risk of end-stage renal disease. The prevalence
      of hypertension among African-Americans has been declining, but remains much
      higher than among White people. Management of hypertension is the best avenue to
      prevent much of the excess burden of end-stage renal disease, but the relative
      merits of different agents and levels of blood pressure control are still under
      study. In addition, individuals with human immunodeficiency virus-related end
      stage renal disease represent a small but rapidly growing number of patients that
      are predominantly African-American. Studies are underway to examine ethnic
      differences and risk factors for the earlier stages of renal disease as well as
      genetic mutations for non-Mendelian forms of end-stage renal disease.

PMID- 9263668
TI  - The circadian pattern of blood pressure: cardiovascular risk and therapeutic
      opportunities.
AB  - It has been known for many years that humans possess internal time clocks that
      regulate multiple physiologic factors (chronobiology). Epidemiologic studies have
      demonstrated that the peak incidence of many diseases, including respiratory
      disease (asthma, allergy), cardiovascular disease (hypotension, angina,
      myocardial infarction, stroke), as well as several others, tends to occur in a
      circadian pattern. In particular, studies utilizing ambulatory blood pressure
      monitoring have demonstrated that blood pressure has a very definite and
      reproducible circadian pattern over a 24-h period. Blood pressure is highest
      during the day; lowest during sleep, and then rapidly increases during the period
      0400 h to 1200 h. Because recent data have demonstrated a possible cause-effect
      relationship between increases in blood pressure and angina, effective
      antihypertensive control in the early morning is desirable. Some once-a-day drugs
      taken in the morning may lose efficacy in the last few hours of the dosing
      interval, resulting in increases in blood pressure during the early morning
      period. In an attempt to ensure peak plasma levels during the early morning
      period, novel, controlled-onset, extended release-delivery systems have been
      developed. Studies using these delivery systems have demonstrated that, when
      dosed at night, these formulations provide maximal plasma levels during the
      period 0600 h to 1200 h, when blood pressure is physiologically rising at its
      greatest rate. The use of drugs designed to have peak efficacy at certain
      desirable times in the circadian pattern is referred to as chronotherapeutics.

PMID- 9263669
TI  - Apoptosis and autoimmunity.
AB  - Apoptotic cell antigens have been identified increasingly as the targets of
      autoantibodies in autoimmune diseases such as systemic lupus erythematosus. This
      review examines evidence supporting the hypothesis that apoptotic cells are a
      primary source of immunogen in lupus, as well as potential mechanisms by which
      tolerance to apoptotic cells may break down.

PMID- 9263670
TI  - The nephritogenic immune response.
AB  - Recent insights into the etiopathogenesis of nephritogenic immune responses are
      derived primarily from experimental models of systemic and organ-specific
      autoimmunity. Genetic analyses and immune-related gene ablation studies indicate
      that multiple independent mechanisms determine disease susceptibility. However,
      full characterization of proximal immunologic events in many diseases awaits
      identification of the renal antigens recognized by nephritogenic lymphocytes.
      Advances in characterization of effector mechanisms include epitope mapping of
      several putative pathogenic glomerular antigens and identification of novel
      pathways of immune-mediated tissue injury, including those involved in glomerular
      tubulointerstitial communication and tubulointerstitial fibrosis. Finally,
      successful interruption of signal transduction pathways and transforming growth
      factor-beta 1 blockade by gene therapy suggest novel approaches to therapeutic
      intervention in immunologic renal injury.

PMID- 9263671
TI  - Cystic kidney diseases.
AB  - The goal of understanding the primary defects that lead to renal cystic diseases
      has proved to be an elusive one, despite 3 decades of physiologic and genetic
      investigation. Within the past 2 years the genes responsible for type 1 and type
      2 autosomal dominant polycystic kidney disease have been identified. The process
      of defining the normal distribution and functions of the proteins encoded by
      these genes as well as the precise pathophysiology of cystogenesis is underway.
      For other major hereditary cystic kidney diseases, chromosomal localization or
      gene identification has also been achieved in recent years. Mouse and rat models
      of renal cystic disease continue to be a rich source of new data on the effect of
      genetic and environmental modifying factors on disease progression as well as
      serving as a preliminary testing ground for novel approaches to management such
      as gene therapy and early dietary modification. Ongoing clinical research
      continues to better define the renal and extra-renal manifestations of autosomal
      dominant polycystic and other renal cystic diseases. It is likely that a clearer
      understanding of the pathophysiology of these diseases will provide important
      insights into the processes that control tissue development and growth, and
      cellular differentiation.

PMID- 9263672
TI  - The prospects for xenotransplantation of the kidney.
AB  - A severe shortage of transplant donors has led to a markedly prolonged waiting
      time for renal transplantation and has thus sparked interest in the use of
      animals in lieu of humans as a source of kidneys for transplantation. Clinical
      application of xenotransplantation is limited in large part by the severe
      immunologic reaction of the recipient against the graft. This immunologic
      reaction is mediated initially by components of natural immunity, such as
      xenoreactive antibodies, complement and natural killer cells, and later by
      elicited humoral and cellular immune responses that act in concert to disrupt the
      function of the endothelial lining of blood vessels. The past few years have
      brought considerable progress in elucidating the molecular and cellular basis of
      xenograft rejection and in developing strategies to overcome it.

PMID- 9263675
TI  - Epidemiology and prevention.

PMID- 9263676
TI  - Renal immunology and pathology.

PMID- 9263674
TI  - Evaluation of the transplant recipient and donor: molecular approach to tissue
      typing, flow cytometry and alternative approaches to distributing organs.
AB  - An enzyme-linked immunosorbent assay test for measuring and characterizing anti
      human leukocyte antigen antibodies in recipient sera received mixed evaluations.
      Enzyme-linked immunosorbent assay and flow cytometry crossmatch tests using
      solubulized donor human leukocyte antigens were introduced New methods for
      allocating kidneys included permissible human leukocyte antigen mismatch, human
      leukocyte antigen amino acid residue match, and kidney size/human leukocyte
      antigen match algorithms.

PMID- 9263673
TI  - Chimerism after organ transplantation.
AB  - Recent evidence suggests that passenger leukocytes migrate after organ
      transplantation and produce persistent chimerism, which is essential for
      sustained survival of the allograft. Here, we describe how this
      hematolymphopoietic chimerism provides an important framework for interpretation
      of post-transplant phenomena and for initiation of therapeutically oriented
      transplantation research.

PMID- 9263677
TI  - Mineral metabolism.

PMID- 9263678
TI  - Parathyroid hormone-related peptide and the parathyroid hormone/parathyroid
      hormone-related peptide receptor in skeletal development.
AB  - Parathyroid hormone-related peptide has recently been shown to have important
      functions in the control of cellular growth and differentiation. Studies using
      knockout and transgenic technology have played a key part in the development of
      our understanding of its physiological role in endochondral bone development and
      adult skeletal homeostasis. Acting, at least partly, through the parathyroid
      hormone/parathyroid hormone-related peptide receptor, parathyroid hormone-related
      peptide profoundly influences chondrocytic and osteogenic cell biology. Further
      understanding of these functions may have important implications in the
      pathophysiology and treatment of human skeletal disorders, including
      osteoporosis.

PMID- 9263679
TI  - Control of nuclear transcription of vitamin D-dependent genes by vitamin D.
AB  - Vitamin D acts on the genome via its active metabolite, calcitriol, which is
      bound to its nuclear receptor (vitamin D receptor) and a DNA response element.
      The characterization of the DNA target of the vitamin D receptor in vitamin D
      activated or -repressed genes and structure-function analysis of the vitamin D
      receptor have led to several advances. These include a better understanding of
      the mechanisms of transactivation via the vitamin D receptor by the description
      of direct and indirect interactions of the vitamin D receptor with the basal
      transcriptional machinery. Physiological evidence for heterodimerization of the
      vitamin D receptor with the retinoid X receptor, and with other liganded or
      unliganded nuclear receptors, has indicated how the genetic response to vitamin D
      can be modulated. This modulation can also be brought about by cooperation
      between vitamin D receptor and transcription factors, by the action of a dominant
      negative isoform of vitamin D receptor, and by cross-talk between the signalling
      pathways for vitamin D and growth factors. These new concepts, plus the
      development of analogues of calcitriol, all indicate considerable progress
      towards vitamin D therapy for several disorders, including renal diseases.

PMID- 9263680
TI  - Regulation of parathyroid cell proliferation.
AB  - The parathyroid normally has very few cells in mitosis but it retains the
      potential to proliferate. In-vivo studies in rats have demonstrated that
      hypocalcaemia and high serum phosphate both lead to an increase in the number of
      proliferating cells, which is relevant to the increased parathyroid cell
      proliferation in chronic renal failure. Hypophosphataemia and 1,25(OH)2D3
      decrease parathyroid cell proliferation. Genetic factors have been defined for
      multiple endocrine neoplasia which includes parathyroid cell hyperplasia, and in
      some parathyroid adenomas there are genetic rearrangements.

PMID- 9263681
TI  - Role of cytokines in renal osteodystrophy.
AB  - Patients with end-stage renal failure present with various debilitating forms of
      renal osteodystrophy characterized either by high bone turnover with or without
      mineralization defect or low bone turnover, that is, adynamic bone disease.
      Alterations in parathyroid hormone and calcitriol production do not completely
      account for the abnormalities in bone turnover. This suggest that other factors
      or mediators, or both, are involved in the regulation of bone turnover. Among
      them, the cytokine systems are of particular interest because of the following:
      cytokine production is altered in uremic patients; there are interactions between
      parathyroid hormone, calcitriol, and cytokines; and cytokines modulate bone cell
      number or activity, or both. Preliminary results of direct assessment of
      cytokines in bone of uremic patients are promising. Future research in this field
      should advance our knowledge of the intricate mechanisms that regulate bone
      turnover in renal osteodystrophy. This could provide a basis for better
      strategies in the control of bone abnormalities in uremic patients.

PMID- 9263682
TI  - Invasive versus non-invasive diagnosis of renal bone disease.
AB  - At present, bone histomorphometry remains the gold standard for the diagnosis of
      the various types of renal bone disease. In the search for a non-invasive method
      of diagnosis, biochemical serum markers of bone remodelling, in addition to serum
      intact parathyroid hormone and aluminium determinations, have been proposed as
      the most reliable tools and are at present widely used in clinical practice.
      Their respective diagnostic values, as separate items and in combined analysis,
      are thoroughly discussed in the present review.

PMID- 9263683
TI  - Imaging of the parathyroid in chronic renal failure: diagnostic and therapeutic
      aspects.
AB  - On the basis of recent advances in our understanding of the pathogenesis of
      chronic renal failure, imaging of parathyroid hyperplasia in chronic dialysis
      patients has become a highly useful tool not only for identification, but also
      for evaluation of the nature of abnormal glands and for various intervention
      strategies. Rational imaging approaches, different from those used for primary
      hyperparathyroidism, should be established for secondary hyperparathyroidism.

PMID- 9263684
TI  - Adynamic bone disease: pathogenesis, diagnosis and clinical relevance.
AB  - In the past several years significant attention has been directed to the study of
      adynamic bone disease in uremic patients. Several reports have provided
      additional information about the prevalence of adynamic bone disease in different
      countries. It has now become clear that the pathogenesis of adynamic bone disease
      cannot be ascribed to one single aetiological factor, but rather to a host of
      complex factors. From recently published papers we have learned about the
      mechanism of downregulation of the parathyroid hormone/parathyroid hormone
      related peptide receptor on osteoblast-like cells, which may be a very important
      step in the pathogenesis of adynamic bone disease. A provocative hypothesis
      attempts to link the widespread use of erythropoietin to the emergence of
      adynamic bone disease-lacking excessive aluminium accumulation. It appears from
      some studies that bone-specific alkaline phosphatase might become a valuable tool
      in differentiating high turnover from low/normal turnover bone disease; however,
      further studies are needed to establish the role of this marker in the diagnosis
      of adynamic bone disease. Several papers discussed the pros and cons of lowering
      the calcium concentration of the dialysate in order to prevent adynamic bone
      disease. The results of these studies help us to understand the pathogenesis and
      the clinical relevance of this lesion in attempts to provide better care for our
      patients.

PMID- 9263685
TI  - Hyponatremia: a re-examination.

PMID- 9263686
TI  - Role of aquaporins in water balance disorders.
AB  - The aquaporins are a recently recognized family of water channels that mediate
      water transport in kidney and in other organs. Aquaporin-2, 'vasopressin
      regulated water channel', is regulated by vasopressin in two ways to account for
      overall control of collecting duct water permeability. First, vasopressin has a
      short-term effect in triggering translocation of aquaporin-2-containing
      intracytoplasmic vesicles to the apical plasma membrane, thus increasing
      principal cell water permeability. Second, vasopressin has a long-term effect in
      increasing the abundance of aquaporin-2 in collecting duct principal cells,
      increasing the maximal attainable water permeability. Using animal models,
      defects in these control mechanisms have been shown to be associated with several
      disorders of water balance, including central diabetes insipidus, congenital
      nephrogenic diabetes insipidus, acquired diabetes insipidus, syndrome of
      inappropriate antidiuretic hormone secretion, and several extracellular fluid
      volume expanded states.

PMID- 9263688
TI  - Recent advances in the understanding of polycystic kidney disease.
AB  - Polycystic kidney disease is characterized by localized autonomous cellular
      proliferation, compartmentalized fluid accumulation within the cysts, and
      intraparenchymal fibrosis of the kidney. The clinical features include renal
      failure, liver cysts, and vascular and cardiac valve abnormalities. Recent
      developments have extended our understanding of cyst formation, fluid secretion,
      and the genetics of polycystic kidney disease. Two causal genes for polycystic
      kidney disease, PKD1 and PKD2, that are responsible for greater than 95% of cases
      of autosomal dominant polycystic kidney disease, have been identified and
      sequenced. The mechanisms of cystogenesis are being uncovered and the phenotypic
      features of cystic epithelial cells are being discovered. This review describes
      recent advances made in the molecular biology of the genetic causes of polycystic
      kidney disease. The mechanistic details of cystogenesis are discussed and
      contrasted with the paradigms that guide current experimental approaches.

PMID- 9263687
TI  - Sodium transporters in health and disease.
AB  - Our understanding of sodium transport defects has exploded in the past 18 months,
      and has provided unique insights into epithelial transport processes and unusual
      clinical syndromes resulting from mutations of specific transporters. These
      genetic disorders disturb sodium balance, with both sodium retaining and sodium
      wasting disorders as the consequence.

PMID- 9263689
TI  - Cell biology of aminoglycoside nephrotoxicity: newer aspects.
AB  - Recent advances in the understanding of the cell biology of aminoglycoside
      antibiotics have answered some questions and opened many new avenues for
      exploration. Binding at the apical surface of proximal tubule cells is now known
      to involve megalin. Once endocytosed, aminoglycosides inhibit endosomal fusion.
      They may also be directly trafficked to the Golgi apparatus. Finally, the
      proximal tubule cell has the ability to inhibit selectively the uptake of
      gentamicin yet maintain endocytosis of other ligands.

PMID- 9263690
TI  - Transforming growth factor-beta in human glomerular injury.
AB  - Overexpression of the cytokine transforming growth factor-beta has been
      identified as the key mediator of chronic progressive kidney fibrosis in
      experimental and human kidney diseases. The renoprotective effects of angiotensin
      II blockade and low-protein diets have recently been linked to downregulation of
      transforming growth factor-beta production. Neutralizing the actions of
      transforming growth factor-beta by decorin gene therapy appears to be a highly
      effective new approach in the treatment of renal fibrosis.

PMID- 9263691
TI  - Endothelin in ischemic acute renal failure.
AB  - The endothelin peptides comprise a family of potent and long-lasting
      vascoconstrictors, to which the renal microcirculation is particularly
      susceptible. Increased renal endothelin expression is observed after a variety of
      injurious stimuli, including ischemia, and persists for days after resolution of
      the initial injury. Autoinduction of its own production is likely to be a central
      mechanism underlying endothelin's prolonged effects. Furthermore, antagonizing
      endothelin reveals its role in maintaining the postischemic glomerular
      dysfunction that typifies ischemic acute renal failure.

PMID- 9263692
TI  - The use of growth factors to increase glomerular filtration rate in chronic renal
      failure patients.
AB  - Insulin-like growth factor-1 has been safely administered to humans with chronic
      renal failure in an attempt to increase glomerular filtration rate. The results
      of short-term studies have been encouraging. Further studies will be required to
      better define the role of this or other growth factors in increasing glomerular
      filtration rate in patients with chronic renal failure.

PMID- 9263694
TI  - Mineral metabolism.

PMID- 9263693
TI  - Pathophysiology of reduced glomerular filtration rate in delayed graft function.
AB  - Delayed graft function is a form of postischemic acute renal failure. It lowers
      glomerular filtration rate in large part by depressing the glomerular
      transcapillary hydraulic pressure difference, the driving force for the formation
      of filtrate. Loss of proximal tubule cell polarity, impaired sodium reabsorption
      and tubuloglomerular feedback-mediated afferent arteriolar constriction are all
      implicated. A link between delayed graft function and chronic allograft injury is
      evident. The ensuing impairment of graft survival makes urgent the need for
      further elucidation of delayed graft function and a search for an effective
      therapy.

PMID- 9263695
TI  - Renal pathophysiology.

PMID- 9263696
TI  - Premenstrual syndrome: current perspectives on treatment and etiology.
AB  - In the past year, randomized controlled clinical trials of treatments for clearly
      diagnosed premenstrual syndrome reported efficacy for serotonergic
      antidepressants and a gonadotropin-releasing hormone agonist. Preliminary data
      suggested efficacy for spironolactone and a carbohydraterich beverage. Several
      neuroendocrine studies have contributed to a growing list of findings that
      suggest an underlying neurobiological vulnerability in premenstrual syndrome.

PMID- 9263697
TI  - Menstrual migraines: etiology, treatment, and relationship to premenstrual
      syndrome.
AB  - Migraine headache is a common condition in women and frequently occurs in
      relation to the menstrual cycle. This article reviews the neuroendocrine etiology
      of menstrual migraine, its possible relationship to premenstrual syndrome, and
      recent developments in treatment strategies for these often refractory headaches.

PMID- 9263698
TI  - Endometrial changes with chronic tamoxifen use.
AB  - Tamoxifen is a nonsteroidal antiestrogenic drug used successfully to reduce
      recurrences in all stages of breast carcinoma. Recent reports have emphasized an
      increased incidence of premalignant and neoplastic endometrial changes that have
      questioned the risk-benefit ratio of this medication. It appears that the use of
      tamoxifen increases the incidence of endometrial abnormalities in 1.2 individuals
      per 1000 women treated with tamoxifen, increasing to 6.3 per 1000 women after 5
      years. However, current evidence suggests that the use of tamoxifen as an
      adjuvant for breast carcinoma overrides the risk of developing endometrial
      neoplasias. It is not clear which long-term method of surveillance is most cost
      effective for these patients. Therefore, individuals should be alerted to the
      potential risks of tamoxifen use. At present, the screening method of choice
      should be decided by each individual practitioner, bearing in mind that any
      vaginal bleeding should be readily investigated. If high-grade hyperplasias of
      the endometrium or cancer are found, management should be tailored in conjunction
      with the physician responsible for the woman's breast care.

PMID- 9263699
TI  - Infertility treatment in women over 40 years of age.
AB  - Women experience a sharp decline in fecundity after the age of 40. Most research
      points to decreasing oocyte competency and ovarian function as the main causes of
      this downward trend. Aggressive treatment with in vitro fertilization, laboratory
      techniques that improve the implantation ability of embryos, and ovum donation
      can help many of these women achieve healthy pregnancies. Such medical advances
      are accompanied by new ethical challenges.

PMID- 9263700
TI  - Implantable hormonal and emergency contraception.
AB  - Recent publications about emergency and implantable contraception focused on
      increasing the awareness about emergency contraceptive methods and on updating
      readers about the controversies surrounding Norplant. Both emergency and
      implantable contraception have excellent safety and efficacy profiles, yet
      neither has realized its potential for widespread use. This review addresses
      these concerns and attempts to place these issues in perspective.

PMID- 9263701
TI  - Use of androgens in postmenopausal women.
AB  - Serum androgen levels decline with age in women, a decline already demonstrable
      prior to menopause. Oestrogen administration is associated with a decrease in
      bioavailable testosterone. Testosterone administration can lead to increases in a
      number of parameters of sexuality, probably by direct neural effects. Androgens
      also have anabolic effects on bone, and do not adversely affect lipids,
      especially when given parenterally.

PMID- 9263702
TI  - Steroid abuse in female athletes.
AB  - Drug abuse in sport attracts considerable media and public interest, particularly
      around the time of major international events such as the Olympic Games. From a
      scientific viewpoint the benefits of drugs to sportspersons have been difficult
      to address. In the case of steroids, the experiments required for proof,
      particularly in women, are unethical. Drug testing is an expensive mechanism for
      deterrence, but there are areas in the scenario where validation data are lacking
      and improvements to the procedures are needed. Testing standards for women cannot
      be based on results from tests in men, and regulations need revision to take
      account of new data.

PMID- 9263704
TI  - Insulin resistance in polycystic ovary syndrome.
AB  - Hyperinsulinaemia is found in 30% of slim and 75% of obese women with polycystic
      ovary syndrome. Despite resistance to insulin action in terms of glucose
      transport, increased insulin levels may cause hyperandrogenaemia by enhancement
      of androgen production in the ovaries where insulin acts as co-gonadotrophin.
      Recent interest in insulin resistance results from the recognition that it
      predisposes to various metabolic abnormalities, and could be involved in the
      pathogenesis of atherosclerosis. Women with polycystic ovary syndrome frequently
      have metabolic disturbances associated with insulin resistance, and recent long
      term follow-up studies have indicated that they also have a higher incidence of
      diabetes and hypertension later in life compared with control populations. This
      review describes the association of hyperinsulinaemia with hyperandrogenism,
      metabolic and circulatory changes in women with polycystic ovary syndrome.
      Special emphasis is placed on recent studies of molecular mechanisms of insulin
      resistance in polycystic ovary syndrome and clinical implications of
      hyperinsulinaemia in these women.

PMID- 9263703
TI  - Investigations in the assessment and management of patients with hirsutism.
AB  - Most hirsute women have polycystic ovaries. The few women who have a more
      sinister cause for their hirsutism can probably be identified by clinical
      symptoms and signs. Therefore, the purpose of investigation is to identify those
      women, and this can probably be best achieved by a first-line measurement of
      serum testosterone. If this is normal, subsequent investigations are only
      required to guide the choice and use of any systemic therapy. It is probably
      unnecessary to measure any endocrine parameters once therapy has been initiated,
      since there is no relationship between these variables and hair growth.

PMID- 9263705
TI  - Premature ovarian failure.
AB  - The past 2 years have seen progress in our understanding of the process of
      premature ovarian failure with identification of molecular causes and
      clarification of the autoimmune targets within the ovary. With the knowledge that
      most women with premature ovarian failure have ovarian follicles on
      ultrasonography, we eagerly await the next therapeutic landmark-the application
      of the preservation or in-vitro maturation of ova.

PMID- 9263706
TI  - New developments in postmenopausal hormone replacement therapy.
AB  - In this review we summarize background data that have steadily accumulated to
      help explain the beneficial actions of oestrogen replacement treatment on
      cardiovascular disease. The range of beneficial actions on the cardiovascular
      system is extraordinary, and goes far beyond the widely acknowledged effects on
      lipoprotein action. We also review recent reports on the beneficial actions of
      oestrogen treatment on Alzheimer's disease and colorectal cancer. The emphasis
      throughout is on understanding the mechanisms of benefit.

PMID- 9263708
TI  - Fertility.

PMID- 9263709
TI  - Reproductive endocrinology.

PMID- 9263707
TI  - Management of multiple gestations complicated by a single anomalous fetus.

PMID- 9263710
TI  - Endoscopic surgery.

PMID- 9263711
TI  - Fluid balance during hysteroscopic surgery.
AB  - Absorption of irrigating solution may involve serious complications during
      hysteroscopic surgery. This absorption occurs mainly into the vessels opened
      during the procedure. Careful perioperative monitoring of the deficit of
      collected irrigating medium during transcervical surgery is mandatory.
      Significant absorption seems to be connected with the development of discrete
      cerebral oedema and nausea, secondary to dilutional hyponatraemia and elevation
      of several amino acids.

PMID- 9263712
TI  - Endometrial ablation.
AB  - Endometrial ablation is associated with a shorter operative time, fewer
      complications, less use of analgesics, a shorter convalescence and a quicker time
      to return to work than hysterectomy in the treatment of menorrhagia. Endometrial
      resection costs the health service provider less money than hysterectomy;
      however, women randomized to hysterectomy have reported slightly higher rates of
      satisfaction than those randomized to endometrial resection.

PMID- 9263713
TI  - Laparoscopic myomectomy and myolysis.
AB  - The indications for operative laparoscopy have expanded greatly over the past
      decade as its many advantages over laparotomy have become recognized.
      Laparoscopic myomectomy as a technique is now clearly described. A monopolar hook
      is used for the uterine incision. After atraumatic enucleation of the myoma, the
      myometrium and serosa are usually sutured, especially if the incision is deep or
      more than 2 cm long. Myomas can be removed by posterior colpotomy. However, the
      development of an electrical cutting device permits easier and quicker removal of
      the myoma through the suprapubic puncture site. Only complicated myomas or those
      which give rise to persistent symptoms despite properly prescribed medical
      treatment, together with those which grow rapidly, require surgery. These
      satisfactory preliminary results must not mask the fact that laparoscopic
      myomectomy is lengthy and difficult, reserved for experienced surgeons with a
      thorough familiarity with endoscopic sutures. Under these conditions,
      laparoscopic myomectomy is possible, even for large myomas (5 cm and over)
      located purely intramurally. However, there are limits, and it is preferable to
      schedule myomas measuring over 8 cm and multiple myomectomy (over two) for
      laparotomy. Although the preliminary results are encouraging, the risk of
      adhesiogenesis on the uterine scar, the quality of the uterine suture and the
      fertility results need to be assessed in the near future.

PMID- 9263714
TI  - How can we avoid adhesions after laparoscopic surgery?
AB  - Although fewer develop than after laparotomy, laparoscopic surgery is still
      associated with adhesion formation. In order to minimize this, nothing replaces
      good surgical technique. Basic principles of microsurgery, liberal irrigation of
      the abdominal cavity and instillation of a large amount of Ringer's lactate at
      the completion of the procedure should be followed. Among adhesion preventing
      substances, adhesion barriers including expanded polytetrafluoroethylene and
      regenerated oxidized cellulose are the most effective. Alternatively, a second
      look laparoscopy to liberate the adhesions can be performed.

PMID- 9263716
TI  - Laparoscopic management of gynecological malignancies.
AB  - The primary surgical management of endometrial and cervical carcinoma requires
      four operations: simple and radical hysterectomy, and pelvic and aortic
      lymphadenectomy. All these four operations can now be carried out
      laparoscopically with significant reduction in morbidity and among the patient
      population that develops these malignancies, namely, the elderly and the obese.
      Moreover, as judged by the number of nodes harvested and the proportion of
      positive nodes, the radicality of laparoscopic lymphadenectomy is equivalent to
      its 'open' counterpart. Thus, laparoscopic management is feasible in almost every
      patient who has carcinoma of the endometrium or cervix. Experience with the
      laparoscopic management of ovarian cancer is more limited. There has been concern
      that the increased frequency of cyst rupture makes laparoscopic management
      inappropriate, but cyst rupture per se does not impair survival provided patients
      are managed appropriately with adjuvant chemotherapy, and all but stage I, grade
      I ovarian cancer is treated with neoadjuvant chemotherapy. Many patients who have
      stage II-IV disease can be satisfactorily 'debulked' laparoscopically, and a
      significant proportion of those who cannot be debulked primarily can be debulked
      laparoscopically after neoadjuvant chemotherapy. The laparoscopic management of
      ovarian cancer promises to be the most active area of advance over the next few
      years.

PMID- 9263715
TI  - Laparoscopic colposuspension and pelvic floor repair.
AB  - True progress was achieved when the laparoscope was first used to explore the
      extraperitoneal space. Up to 25 reports on laparoscopic bladder neck surgery have
      been published in the past five years, and a few present prospective data.
      Laparoscopic surgery for the other aspects of pelvic floor reconstruction is
      still only timidly mentioned and in the case study stage.

PMID- 9263717
TI  - Managed care in obstetrics.
AB  - Managed care has marched relentlessly through all fields of obstetric care:
      individual and group practices, proprietary hospitals and academic medical
      centers, and public health systems. Emphasis on cost containment while preserving
      high quality has driven the redesign of healthcare delivery. A number of models
      for providing effective and less expensive obstetric care are now being examined
      in the USA and abroad. Increased market penetration by managed care will also
      exert profound and possibly harmful effects on traditional academic teaching
      institutions. These organizations must adapt to this new environment or face the
      erosion of physician support and training bases. Ultimately, significant moral
      and ethical dilemmas will arise when patients' best interests for care are being
      continually brought into conflict with the physician's need to earn a living.

PMID- 9263718
TI  - The managed care of early pregnancy problems.
AB  - There is an increasing trend towards non-invasive diagnosis and conservative
      treatment for early pregnancy problems. Although there are enormous potential
      benefits for women being treated thus, the ideal treatment methods and diagnostic
      algorithms have yet to be elucidated. Further large-scale studies are required.

PMID- 9263719
TI  - Managed care in benign gynecology.
AB  - The invasion of managed care into the American health system has led to drastic
      and potentially salutary changes in both the locus and delivery of care. With a
      focus on cost-effectiveness and decisions based on outcomes analysis, the
      rationale of many traditional management options has been called into question. A
      discussion of how the implementation of this new evidence-based, cost-centered
      gold standard has affected the management of four benign gynecologic processes is
      the purpose of this update.

PMID- 9263720
TI  - Managed care of hormone replacement therapy in the menopause.
AB  - The principles of managed care are more difficult to apply to preventive medical
      treatments, such as hormone replacement therapy, than to the investigation and
      treatment of established disease. In addition to an ageing society with increased
      health demands, the use of hormone replacement therapy is increasing in most
      developed countries. Clinical guidelines for the counselling of post-menopausal
      women and the use of hormone replacement therapy have been prepared by the
      American College of Physicians. There is limited information about the benefits
      and risks of hormone replacement therapy from randomized prospective studies and
      these guidelines are based on the best available data from observational studies
      and meta-analysis. More secure data will become available within the next decade
      from long-term studies that are currently in progress. Managed care proposals for
      hormone replacement therapy must be flexible enough to adjust to new data as they
      become available while recognizing that, given current knowledge, hormone
      replacement is healthcare-cost-effective for the vast majority of menopausal
      women.

PMID- 9263721
TI  - Antiphospholipid antibodies, infertility and recurrent miscarriage.
AB  - Antiphospholipid antibodies are found in 15% of women with recurrent miscarriage.
      These women have only a 10% live birth rate in subsequent pregnancies in which no
      pharmacological treatment is given. Pregnancy loss is often attributable to
      uteroplacental insufficiency subsequent to placental thrombosis. Treatment with
      low dose aspirin improves the live birth rate amongst women with antiphospholipid
      antibodies to 40% but this is further and significantly increased to 70% when
      they are treated with aspirin together with low-dose heparin.

PMID- 9263722
TI  - Endoscopic surgery.

PMID- 9263723
TI  - Managed care.

PMID- 9263724
TI  - Clinical chemistry in laboratory medicine in Europe--past, present and future
      challenges.
AB  - European experts in clinical laboratory sciences have different backgrounds, and
      development of expertise in this field started more than 100 years ago. Specific
      national activities have created the heterogeneity that now exists amongst the
      academic professional membership of more than 40 scientific societies in Europe.
      The recent political changes have in addition contributed to the rapidly changing
      profile of Clinical Chemistry and related fields. Based on a questionnaire
      answered by 31 national representatives, the past, present and future aspects of
      the European Clinical Laboratory are reviewed. Of the more than 30,000 members of
      national societies, the majority studied medicine (40.1%), chemistry (27.2%) and
      pharmacy (21.1%) with large national differences in relative percentages. Post
      graduate education is provided by two thirds of the national societies. In most
      European countries the same experts cover not only clinical chemistry but also
      haematology, haemostaseology, immunology and transfusiology. National quality
      assurance programmes are said to be established in 25 countries, but mandatory in
      only 11 of them. Of the future challenges, the implementation of request
      strategies were named most often, with interpretative reports and preanalytical
      aspects estimated as similarly important. It was thought that information
      technology and new scientific developments would make the greatest impact in the
      coming years, with economic pressure being the major limiting factor. Despite
      these limitations an increase in the number of tests is anticipated by most
      representatives, supporting the assumption of an increasing role of the clinical
      laboratory in future clinical medicine.

PMID- 9263725
TI  - Clinical laboratory work--concepts and terms.
AB  - An appropriate term is sought for the concept embracing the different types of
      clinical laboratory work. The defining characteristics of the concept are
      therefore described, i.e. site, goal, objectives, activity, field, and
      participating professionals. It is proposed that the superordinate concept should
      be "medicine" while the subordinate concept under discussion is defined on the
      basis of the characteristics, thereby distinguishing it from coordinate concepts,
      i.e. from other branches of medicine. The principles used for establishing
      existing terms in other branches of medicine are presented, together with a
      discussion of existing terms in the clinical laboratory field. It is suggested
      that the current term 'laboratory medicine' has several advantages. The workplace
      may be called a 'department of laboratory medicine' or 'clinical (or medical)
      laboratory'. It is further suggested that the term 'clinical chemistry' should
      not generally be replaced by 'clinical biochemistry'.

PMID- 9263726
TI  - Activated protein C resistance--a major risk factor for thrombosis.
AB  - Resistance to activated protein C is a recently detected phenomenon that has
      gained a rapid acceptance as a major risk factor for venous thromboembolism. The
      phenotypic expression of resistance to activated protein C is characterized by a
      poor response to the anticoagulant activity of activated protein C, a key enzyme
      in the down-regulation of blood coagulation, which causes a disposition for a
      hypercoagulable state. At least 90% of the cases with resistance to activated
      protein C are explained by a point mutation in the gene for coagulation factor V,
      resulting in replacement of an Arg to Gln at position 506 (factor V:Q506, often
      denoted factor V Leiden), one of the three activated protein C cleavage sites in
      activated factor V. The mutation is inherited as an autosomally dominant trait
      and has a prevalence of 2% to more than 10% in the general Caucasian population.
      A number of clinical studies, using different inclusion criteria, show a
      prevalence of activated protein C resistance of 20-60% among patients with venous
      thromboembolism. The actual thrombotic risk is moderate with an odds ratio of 5-7
      but its high prevalence makes it by far the most important inherited risk factor
      known today, even higher than the sum of contributions from inherited
      deficiencies of antithrombin, protein C and protein S. Recent data suggest that
      activated protein C resistance, which is not due to factor V:Q506 and which
      appears to be acquired, is also a risk factor for venous thrombosis and for
      cerebral ischaemic disease. A decreased response to activated protein C is common
      during pregnancy and during use of oral contraceptives, but the clinical
      relevance of these findings have yet to be determined. The activated protein C
      resistance phenotype is typically diagnosed with an activated partial
      thromboplastin time-based assay, which detects factor V:Q506-dependent as well as
      acquired activated protein C resistance. However, the sensitivity and specificity
      for the factor V mutation are usually below 90%. Coagulation instruments with a
      turbidimetric or photometric clot detection principle generally provide a better
      performance as compared to electromechanical instruments. The activated partial
      thromboplastin time test requires careful control of preanalytical variables and
      platelet contamination should be below 1% since otherwise a falsely low activated
      protein C response will be obtained. A sensitivity and specificity of close to
      100% for factor V:Q506 is obtained in a modified activated partial thromboplastin
      time test using predilution of sample plasma with factor V deficient plasma. The
      influence of preanalytical variables in this assay is minor. A number of
      polymerase chain reaction-based methods, some of them allele-specific, have been
      published, which provide convenient and objective confirmation of the factor V
      mutation. Thrombotic events are often triggered through the presence of a
      combination of inherited and circumstantial risk factors. The high prevalence of
      activated protein C resistance raises the issue whether it would be cost
      beneficial to screen for this trait in connection with surgery, pregnancy and
      oral contraceptives. Some data already support this, but prospective studies will
      be necessary to delineate under which circumstances this might be implicated.

PMID- 9263727
TI  - Superoxide dismutase activity in lymphocytes and polymorphonuclear cells of
      diabetic patients.
AB  - Copper-zinc superoxide dismutase (Cu,Zn-superoxide dismutase) activity was
      evaluated in lymphocytes and polymorphonuclear cells of insulin-dependent (n =
      33) and non-insulin-dependent (n = 34) diabetic patients. A commercial method for
      the measurement of superoxide dismutase activity was adapted for use on a
      discrete analyser and evaluated for interference by other antioxidants with
      superoxide anion-scavenging properties. In comparison to healthy control subjects
      (n = 32), a significantly lower Cu,Zn-superoxide dismutase activity was found in
      both lymphocytes and polymorphonuclear cells of insulin-dependent (2.08 +/- 0.58
      vs. 1.70 +/- 0.46 U/mg protein, p < 0.05, and 1.06 +/- 0.46 vs. 0.64 +/- 0.40
      U/mg protein, p < 0.001, respectively) and non-insulin-dependent diabetic
      patients (2.08 +/- 0.58 vs. 1.61 +/- 0.48 U/mg protein, p < 0.01, and 1.06 +/-
      0.46 vs. 0.53 +/- 0.24 U/mg protein, p < 0.001, respectively). There was a week,
      but significant negative correlation between age and Cu,Zn-superoxide dismutase
      activity in lymphocytes and polymorphonuclear cells (r = -0.22 and r = -0.28, p <
      0.05, respectively), whereas no influence of gender, diabetes duration and
      glycaemic control was observed. The results indicate that diabetes mellitus could
      elicit a significant disturbance in superoxide anion-scavenging potential of
      lymphocytes and polymorphonuclear cells.

PMID- 9263728
TI  - Diagnostic value of lactate dehydrogenase isoenzyme pattern in pleural effusions.
AB  - Lactate dehydrogenase isoenzymes have been used to classify the nature of pleural
      effusion. Nevertheless, studies have reported conflicting results. The objective
      of this study was to evaluate the diagnostic value of lactate dehydrogenase
      isoenzymes in the analysis of pleural effusions. Pleural fluid samples obtained
      from three respective diagnostic groups: group I transudate (n = 23), group II
      parapneumonic effusion (n = 29) and group III malignant effusion or pleuritis
      carcinomatosa (n = 41) were evaluated. Total lactate dehydrogenase activity and
      lactate dehydrogenase (LDH) isoenzyme pattern were significantly different
      between transudative (group I) and exudative (group II and III) effusions. Group
      II and III showed a low percentage of LDH1 (p < 0.001), whereas the percentages
      of LDH4 (p < 0.001) and LDH5 (p < 0.001) were higher compared to group I.
      Moreover, in exudative effusions the percentage of LDH1 (p < 0.005), LDH4 (p <
      0.005), as well as LDH5 (p < 0.005) were significantly different between
      parapneumonic and malignant effusions. In contrast to relative lactate
      dehydrogenase isoenzyme values, the absolute values of lactate dehydrogenase
      isoenzymes did not differ between group II and group III. Logistic regression
      analysis yielded a strong discrimination between group I and II+III,
      simultaneously using lactate dehydrogenase, glucose and protein as explanatory
      variables. Logistic regression analysis yielded only a weak discrimination
      between group II and III, simultaneously using lactate dehydrogenase, glucose and
      the absolute values of LDH2 and LDH4 as explanatory variables. In conclusion, the
      lactate dehydrogenase isoenzyme pattern differed between pleural effusions of
      transudative and exudative origin. However, including lactate dehydrogenase
      isoenzyme activities in the biochemical work-up of pleural effusions did not
      reveal an additional discriminatory value in the assessment of the classification
      of these effusions.

PMID- 9263729
TI  - Serum pooling lowers cholesterol recovery.
AB  - Matrix effects hinder the transferability of accuracy for cholesterol. A general
      assumption is that pooled and individual samples yield similar results. We tested
      the hypothesis that serum-pooling affects the recovery for cholesterol. We pooled
      100 serum samples, determining cholesterol of pool and of the individual samples
      with Hitachi 717 and 914. Over twenty days, we daily determined cholesterol of
      individual and pooled samples, using a Hitachi 736 and 747 analyzers. For the
      hundred-sample pool, the pool was 1.1 to 1.5% lower than the individual samples.
      With the daily pool study, the ratio of 747 to 736 was 1.7% lower for the pooled
      compared with the individual samples. Therefore, pooling of serum samples causes
      a decreased recovery, averaging from 1.1-1.7%, and representing 37-57% of the
      allowable bias for cholesterol (< 3%), and it is thereby significant.

PMID- 9263730
TI  - Paediatric reference values for urinary catecholamine metabolites evaluated by
      high performance liquid chromatography and electrochemical detection.
AB  - The majority of the published reference range data on catecholamines excretion by
      healthy children is incomplete and often contradictory (1). We assayed in the
      urines of 127 healthy children the values of the catecholamines (norepinephrine,
      epinephrine, dopamine) and their methylated metabolites (normetanephrine,
      metanephrine, 3-methoxytyramine) for the determination of paediatric reference
      ranges. Data were expressed as micrograms/24 h, mumol/24 h and mmol/mol
      creatinine. An isocratic HPLC procedure by ion-pair reversed phase chromatography
      on a C18 column, using a single mobile phase containing formic acid,
      acetonitrile, diethylamine and octane sulphonic acid (ion pairing agent),
      permitted the separate assay of the various fractions of total catecholamines.
      The relations between each biogenic amine and age were studied and reference
      values were determined as a function of age.

PMID- 9263731
TI  - Determination of 18 beta-glycyrrhetinic acid in human serum using the fully
      automated ALCA-system.
AB  - We report a method for the determination of 18 beta-glycyrrhetinic acid
      (glycyrrhetinic acid) in human serum using the ALCA-system. The technology of the
      ALCA-system is based on the principles of adsorptive and desorptive processes
      between liquid and solid phases. The assay is run fully automated and selective.
      Procedural losses throughout the analysis are negligible, thereby allowing for
      external calibration. The calibration curve is linear up to 10 mg/l and
      concentrations as low as 10 micrograms/l are detectable. CV is 2.5% for within-
      and 7.5% for between-assay precision at a level of 50 micrograms/l and 1.2% for
      within- and 8.5% for between-assay precision at a level of 500 micrograms/l.
      Specific and expensive reagents are not necessary and time-consuming manual
      operations are not involved. This assay can be selected from a wide spectrum of
      methods at any time. Thus, the present method is well-suited for drug monitoring
      purposes in the routine laboratory. In a pharmacokinetic study we measured serum
      levels of glycyrrhetinic acid in ten healthy young volunteers after ingestion of
      500 mg glycyrrhetinic acid. Maximum levels of glycyrrhetinic acid were 6.3 mg/l 2
      to 4 hours after ingestion. Twenty-four (24) hours after ingestion seven probands
      still had glycyrrhetinic acid levels above the detection limit with a mean level
      of 0.33 mg/l.

PMID- 9263732
TI  - Identification of apolipoprotein E polymorphisms using temperature cycled primer
      oligo base extension and mass spectrometry.
AB  - The isothermal Primer Oligo Base Extension (PROBE) reaction combined with matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry for
      diagnostic product detection as recently introduced by our group is modified to
      incorporate temperature cycling during the primer extension step, resulting in
      enhanced levels of diagnostic product generation. Utilizing temperature cycled
      PROBE, the identities of two apolipoprotein E polymorphisms (codons 112 and 158)
      for differentiation of epsilon 2/epsilon 3, epsilon 3/epsilon 3, epsilon
      3/epsilon 4, and epsilon 4/epsilon 4 genotypes were simultaneously determined.
      Primers specific for each site are extended by a series of bases unique to the
      identity of that variable site, producing low mass diagnostic products (M(r) <
      9000) highly amenable to detection by mass spectrometry. The temperature cycled
      PROBE method has yielded unambiguous and correct diagnoses for all samples tested
      thus far. The increased amount of diagnostic product generated per primer by the
      cycling method makes possible faster spectrum acquisition due to the increased
      signal intensity, critical for future automated measurement of such samples.

PMID- 9263733
TI  - Mean corpuscular volume-dependent deviations in red blood cell distribution width
      between Sysmex NE-8000 and SF-3000.
AB  - Values for red blood cell distribution width yield information concerning size
      heterogeneity of red blood cell populations. Comparative studies between various
      haematology analysers are obligatory to quantify apparatus-dependent deviations
      with respect to accuracy and subsequent consequences with respect to clinical
      interpretation of results. In this study a comparative assessment is performed
      between a Sysmex SF-3000 and NE-8000 Haematology Analyser. Fifty-four specimens
      with abnormal red blood cell volumes and a hundred specimens from apparently
      healthy subjects were assayed. Systematic deviations in values concerning red
      blood cell distribution width are demonstrated to show a tendency to decrease
      towards higher mean corpuscular volume values.

PMID- 9263734
TI  - Endogenous interferences on a DAX system: effects of haemolysis and
      hyperbilirubinaemia on creatinine and enzyme determinations.

PMID- 9263735
TI  - Evaluation of plasma (1-->3)-beta-D-glucan measurement by the kinetic
      turbidimetric Limulus test, for the clinical diagnosis of mycotic infections.
AB  - The present multicentre clinical study was conducted to assess the clinical
      utility of a new diagnostic method for deep mycosis in which (1-->3)-beta-D
      glucan, a fungal cell wall component existing in plasma, was quantitatively
      measured by the kinetic turbidimetric Limulus test (WB003). Plasma (1-->3)-beta-D
      glucan concentrations were 0.57 +/- 0.10 microgram/l in 92 healthy subjects and
      0.62 +/- 0.32 microgram/l in 26 patients with non-mycotic diseases (disease
      control group). In comparison with these healthy subjects and patients with non
      mycotic diseases, patients with mycosis had significantly higher plasma (1-->3)
      beta-D-glucan concentrations: 19.63 +/- 73.28 micrograms/l in 12 patients with
      candidaemia, 11.28 +/- 21.42 micrograms/l in 7 patients with urinary Candida
      infection, 4.84 +/- 12.71 micrograms/l in 5 patients with pulmonary candidiasis,
      and 12.21 +/- 31.31 micrograms/l in 4 patients with invasive pulmonary
      aspergillosis. On the statistical analysis of these data, a cut-off value was set
      at 1.0 microgram/l. Using this cut-off value, 3 patients with pulmonary
      cryptococcosis and 4 patients (4/6) with pulmonary aspergilloma were all negative
      with low plasma (1-->3-beta-D-glucan levels. The test WB003 provided equivalent
      or higher efficiency of diagnosis of candidiasis and aspergillosis, in comparison
      with commercially available antigen detection kits, demonstrating its utility as
      a diagnostic reagent. It may also be useful in assessing therapeutic
      effectiveness when used periodically after treatment.

PMID- 9263736
TI  - The history of International Congresses of Clinical Chemistry, 1954-1996.
AB  - Between 1954 and 1996 a total of 16 International Congresses of Clinical
      Chemistry were held. Their main features are reviewed: their size and location;
      organisation and costs; the awards made to eminent clinical chemists; the
      publication of congress proceedings; the scientific content of congresses; and
      the role of industry. These have all changed over this period in a way which
      reflects the development of clinical chemistry. Although these congresses are
      becoming increasingly expensive, and cannot satisfy the needs of everyone, they
      are unique in providing a comprehensive and up-to-date overview of the subject
      and enabling clinical chemists from different countries to meet and exchange
      ideas and experiences.

PMID- 9263737
TI  - Pathobiology and consequences of the discovery of the hepatitis G virus.

PMID- 9263738
TI  - Decreased sensitivity to insulin-like growth factor I in Turner's syndrome: a
      study of monocytes and T lymphocytes.
AB  - Turner's syndrome is characterized, amongst other things, by growth retardation
      with high serum levels of insulin-like growth factor 1 (IGF-I) in relation to
      growth, by a tendency to autoimmune disease and by insulin resistance with
      hyperlipidaemia. Assuming a role for IGF-I subresponsiveness in the last two
      features, the present study was designed to evaluate in patients with Turner's
      syndrome their monocyte/macrophage response to growth hormone (GH) and to IGF-I
      with respect to low-density lipoprotein (LDL) degradation and to the monocyte
      dependent lymphocyte proliferation. Nineteen patients with Turner's syndrome and
      puberty-matched control subjects were studied. Monocytes were isolated from the
      blood of the patients and the control group, and cultured to develop into
      macrophages. The cells were then incubated with 125I-labelled LDL (25 micrograms
      of protein mL-1) in the absence or presence of 50 ng mL-1 IGF-I or GH, and
      cellular lipoprotein degradation was determined. GH and IGF-I effects on T-cell
      proliferation were measured in autologous mixed lymphocyte reaction
      Monocytes/macrophages degradation of LDL was lower in Turner's syndrome patients
      than in control subjects (P < 0.05). IGF-I stimulated LDL degradation by 42 +/-
      8% in the control subjects and by only 16 +/- 7% in Turner's syndrome patients (P
      < 0.05). Control lymphocyte proliferation in AMLR was significantly augmented by
      50-100 ng mL-1 GH or IGF-I. Lymphocytes derived from peripheral blood of Turner's
      syndrome patients remained almost unaffected by either GH or IGF-I. Measurement
      of IL-2 secretion by purified blastoid T lymphocytes-I. revealed a significant
      augmentation by 100 ng mL-1 GH and by 50-100 ng mL-1 IGF-I in control subjects,
      and almost no response in Turner's0 ng syndrome. Turner's syndrome is associated
      with decreased sensitivity of peripheral blood mononuclear cells to GH and to IGF
      I, as is evident by the reduction in LDL degradation, monocyte-stimulated T
      lymphocyte proliferation and IL-2 secretion by blastoid T cells.

PMID- 9263739
TI  - Decreased sensitivity to insulin-like growth factor I as a cause of growth
      failure in Turner's syndrome?

PMID- 9263740
TI  - Chronic administration of propranolol improves vascular contractile
      responsiveness in portal hypertensive rats.
AB  - Propranolol is used clinically as a prophylactic drug to prevent oesophageal
      variceal bleeding in cirrhotic patients with portal hypertension. Vascular
      hyporesponsiveness is a common characteristic of the portal hypertensive state.
      The present study aimed to investigate whether chronic administration of
      propranolol could improve vascular responsiveness in portal hypertensive rats.
      Portal hypertension was induced by partial portal vein ligation (PVL). Sham
      operated rats served as controls. There were four study groups: PVL-propranolol
      group (portal hypertensive rats receiving propranolol), PVL-vehicle group (portal
      hypertensive rats receiving saline), sham-propranolol group (sham-operated rats
      receiving propranolol) and sham-vehicle group (sham-operated rats receiving
      saline). Propranolol (30 mg kg-1 day-1) or saline was given for 9 days via
      gastric gavage starting 1 day before ligation and thereafter. Then, the superior
      mesenteric artery was removed from each group for contractile study after
      haemodynamic measurement. In portal hypertensive rats, propranolol significantly
      alleviated the hyperdynamic state, including portal pressure, cardiac index and
      total peripheral resistance in the treated group compared with the vehicle group.
      The maximal contractile responses to KCl and vasopressin in mesenteric artery
      were significantly greater in the sham-vehicle group than in the PVL-vehicle
      group. Long-term propranolol treatment enhanced the contractile reactivity of
      mesenteric artery to KCl and vasopressin in PVL rats, and the contractile
      profiles were corrected towards those in sham-treated animals. In contrast,
      propranolol treatment decreased heart rate, mean arterial pressure and cardiac
      index but did not alter the contractile responsiveness of sham-operated rats.
      These results showed that, in portal vein stenosed rats, long-term treatment with
      propranolol improved arterial contractile reactivity together with portal
      pressure reduction. The propranolol effect on vascular reactivity is probably
      related to haemodynamic improvement, instead of a direct contractile effect on
      the vasculature.

PMID- 9263741
TI  - Effect of propranolol on vascular hyporesponsiveness in cirrhosis.

PMID- 9263742
TI  - Acute saline infusion induces extracellular acidification and activation of the
      Na+/H+ exchanger in man.
AB  - The effect of acute expansion of the extracellular fluid volume (ECV) with
      isotonic (0.9%) saline on the activity of the lymphocyte Na+/H+ antiport (NHE)
      was studied in a total of 18 healthy volunteers. Saline was infused at a constant
      rate so that 4 mmol kg-1 b.w. was administered over 2 h. NHE activity was
      measured by quantifying cytosolic pH (pHi) recovery following acidification of
      the cells with propionic acid and by pH clamping at various pHi values between
      7.2 and 5.8 using nigericin. Both methods demonstrate NHE activation associated
      with intravenous saline infusion, the kinetic difference being a marked decrease
      in the Hill coefficient n from 3.28 +/- 0.21 (SEM) to 2.22 +/- 0.11 in the
      absence of changes in baseline pHi (7.14 +/- 0.02 vs. 7.08 +/- 0.02; P = 0.15),
      Vmax (42.8 +/- 2.7 vs. 48.1 +/- 2.8 mmol L-1 min-1; P = 0.08) and pK (6.32 +/-
      0.04 vs. 6.35 +/- 0.02). NHE activation was associated with significant decreases
      in serum chloride (P = 0.016), calcium (P = 0.008), total cholesterol (P =
      0.008), low-density lipoproteins (P = 0.016) and high-density lipoproteins (P =
      0.008). Moreover, saline infusion induced extracellular acidification with a
      decrease in pH from 7.39 +/- 0.01 to 7.37 +/- 0.01 (P = 0.016), HCO3- from 23.3
      +/- 0.43 mmol L-1 to 21.3 +/- 0.25 mmol L-1 (P = 0.008) and base excess from 
      1.03 +/- 0.38 mmol L-1 to -3.00 +/- 0.31 mmol L-1 (P = 0.008). Our results show
      for the first time that acute ECV expansion with isotonic saline is followed by
      an activation of the lymphocyte NHE. The underlying mechanism(s) remain to be
      investigated. However, the demonstration in our study of marked changes in acid
      base balance induced by acute saline points to a possible inter-relationship of
      antiporter activation and extracellular acidification.

PMID- 9263743
TI  - Can the Na+/H+ exchange serve as an intermediate phenotype for essential
      hypertension?

PMID- 9263744
TI  - Thrombosis triggered by severe arterial lesions is inhibited by oral
      administration of a glycoprotein IIb/IIIa antagonist.
AB  - Platelet aggregation and thrombosis play an important role in the onset of acute
      coronary events. Regardless of the stimulus for activation, platelet thrombus
      formation is ultimately regulated through the IIb/IIIa receptor complex. The
      effects of oral administration of xemilofiban, a non-peptide mimetic of the RGDF
      sequence of the IIb/IIIa receptor complex, on thrombus formation were evaluated
      in a canine model. Xemilofiban significantly reduced platelet deposition on
      severely damaged arterial wall. Platelet deposition was reduced at both low (13
      +/- 1 from 56 +/- 18 x 10(6) platelets cm-2; P < 0.05) and high (23 +/- 2 from
      111 +/- 21 x 10(6) platelets cm-2; P < 0.01) shear rates. Platelet deposition was
      reduced to a monolayer as seen by electron microscopy (platelet-vessel wall
      interaction). Therefore, the availability of an orally active IIb/IIIa antagonist
      for chronic use may have significant value in preventing thrombus formation in
      those clinical situations associated with severe arterial injury, such as
      atherosclerotic plaque disruption.

PMID- 9263745
TI  - Stimulation of arginine vasopressin secretion by a small increase in blood
      ionized calcium in normal men.
AB  - Evidence has been provided for an increase in baseline serum corticotrophin
      (ACTH) levels in response to a rise in circulating ionized calcium (Cai) levels
      within the physiological range. In order to establish whether small Cai
      increments are also able to modify the basal secretion of arginine vasopressin
      (AVP), we infused calcium gluconate through an intravenous infusion pump in eight
      healthy male subjects (25-31 years old). Serum Cai, ACTH and AVP concentrations
      were measured every 10 min over an infusion period lasting 90 min. A significant
      progressive rise in serum Cai (baseline: 42 +/- 0.9 mg dL-1; 90 min: 47.2 +/- 0.9
      mg dL-1, P < 0.001), ACTH (baseline: 30.7 +/- 1.3 pg mL-1; mean peak at 80 min:
      37.4 +/- 2.4 pg mL-1, P < 0.01) and AVP levels (baseline: 2.1 +/- 0.6 pg mL-1;
      mean peak at 80 min: 3.2 +/- 0.5 pg mL-1, P < 0.01) was observed during calcium
      infusion. Furthermore, a significant positive correlation (r = 0.71; P < 0.001)
      was observed between ACTH and AVP responses to calcium infusion at 60, 70, 80 and
      90 min. These data demonstrate that AVP secretion is stimulated by a slight rapid
      increase in serum Cai levels even though absolute serum Cai levels remain within
      the normal range. In addition, the positive correlation between Cai-induced ACTH
      and AVP increments suggests that AVP plays a releasing role on ACTH secretion
      during calcium infusion.

PMID- 9263746
TI  - Western blotting of NC1 type IV collagen fragments in human plasma.
AB  - Collagen IV matrix of glomerular basement membrane may be involved in the
      development of various renal diseases, e.g. diabetic nephropathy. An
      immunoblotting method for the detection of the carboxy-terminal non-collagenous
      (NC1) domain of type IV collagen in plasma was developed. The high sensitivity
      down to the picogram range enabled characterization of NC1(IV) fragments in human
      blood for the first time. Both Western blotting and gel filtration chromatography
      coupled with an enzyme-linked immunoassay surprisingly revealed that the NC1(IV)
      related components are bound to the fibrin clot forming during blood coagulation.
      About 40% of the NC1(IV) fragments in plasma had an apparent molecular mass
      higher than 340,000. Abnormal NC1(IV) immunoblot patterns were observed in about
      50% of patients with insulin-dependent (n = 20) and non-insulin-dependent (n =
      20) diabetes mellitus compared with less than 7% in healthy control subjects (n =
      30). There were no obvious associations between abnormal immunoblots and stage of
      nephropathy or glycaemic control in diabetic subjects.

PMID- 9263747
TI  - Effects of hemicolectomy on bile acid metabolism in relation to colon
      carcinogenesis in man.
AB  - Bile acids are probably important in colon carcinogenesis. Regional differences
      in bile acid metabolism within the colon were studied to illuminate the
      preferential distal occurrence of colon cancer in Western countries. Faeces (24
      h) were collected for bile acid measurement from 25 patients with hemicolectomy
      (nine left and 16 right) and 17 adenoma patients with an intact colon (control
      subjects). Duodenal bile and cytolytic and alkaline phosphatase activity of
      faecal water were also studied. The median percentage of deoxycholic acid (DCA)
      was lower in the hemicolectomy groups [left 48% (range 38-57%), right 45% (2-62%)
      vs. control subjects 59% (38-70%), P < 0.05]. In duodenal bile, the proportion of
      DCA in left [4% (1-25%)] was lower than in the patients with right hemicolectomy
      [19% (0-69%)] and control subjects [24% (7-50%)] P < 0.05. Faecal concentration
      of protonated DCA was higher in those with right hemicolectomy (0.101 mumol g-1)
      than in those with left hemicolectomy (0.048 mol g-1), which coincided with a
      higher cytolytic [right 49% (3-93%), left 2% (1-37%)] and alkaline phosphatase
      activity [right 6.7 U mL-1 (1.2-40.1 U mL-1), left (2.0 U mL-1 (1-25.7 U mL-1),
      both P < 0.02]. These findings suggest differences in bile acid metabolism
      between the proximal and distal colon that may contribute to the disparity in
      cancer risk.

PMID- 9263749
TI  - Low-density lipoprotein-induced formation of nitric oxide by cultured vascular
      smooth muscle cells of the rat.
AB  - There is evidence that low-density lipoprotein (LDL) plays a crucial role in
      atherogenesis. On the cellular level, LDL has been shown to activate a number of
      mechanisms involved in atherogenesis and vasoconstriction. Local immoderate
      vasoconstriction is physiologically antagonized by nitric oxide, which is
      released from the endothelium. To find out whether LDL also influences the
      synthesis of nitric oxide in vascular smooth muscle cells, both the conversion of
      arginine to citrulline and the production of nitrite were determined as a measure
      of nitric oxide formation. After incubation of rat vascular smooth muscle cells
      with native LDL (25 micrograms mL-1) for 24 h, the production of both L-[14C]
      citrulline [39600 (3600) cpm mg-1 cell protein] and nitric oxide [2.95 (0.56)
      mumol L-1] were about twice and 1.5-fold the amount of the corresponding values
      in untreated cells (mean +/- SD, P < 0.05, n = 4). Oxidized LDL was less
      effective than the native form. The presence of the arginine analogue NG-methyl-L
      arginine reduced citrulline production dose-dependently but augmented DNA
      synthesis, both induced by LDL. In addition, the lipoprotein caused a 1.6-fold
      increase in cyclic GMP production following a 24-h incubation [control = 10.9
      (3.8) pmol mg-1 cell protein, P = 0.016]. The results suggest that native LDL
      might partly impair its atherogenic potential on the vasculature by stimulating
      the production by smooth muscle cells of both nitric oxide and cyclic GMP.

PMID- 9263748
TI  - Increased activity of platelet-activating factor acetylhydrolase in low-density
      lipoprotein subfractions induces enhanced lysophosphatidylcholine production
      during oxidation in patients with heterozygous familial hypercholesterolaemia.
AB  - Patients with heterozygous familial hypercholesterolaemia (FH) have elevated
      plasma concentrations of low-density lipoprotein (LDL) and develop premature
      atherosclerosis. There is increasing evidence that oxidative modification of LDL
      is important for the pathogenesis of atherosclerosis, and the LDL-associated
      platelet-activating factor acetylhydrolase (PAF-AH) seems to play a key role in
      LDL oxidation by hydrolysing the oxidized phospholipids of phosphatidylcholine
      (PC) and producing lysophosphatidylcholine (lyso-PC). We measured the total serum
      and high-density lipoprotein (HDL) levels of PAF-AH activity and studied the
      distribution of PAF-AH activity among three LDL subfractions isolated by gradient
      ultracentrifugation in 15 patients with heterozygous FH and 13 normolipidaemic
      control subjects. We also determined the lyso-PC production in each LDL
      subfraction during Cu2(+)-induced oxidation in vitro. The total serum PAF-AH
      activity in heterozygous FH patients was significantly higher than in control
      subjects, whereas the HDL-associated PAF-AH activity, expressed as a percentage
      of total serum PAF-AH activity, was significantly lower in the FH patients than
      in control subjects (13.9 +/- 6.6% vs. 30.6 +/- 4.4%, P < 0.001). Among the LDL
      subfractions, the PAF-AH activity in both normolipidaemic control subjects and FH
      patients, expressed as nmol mg-1 protein min-1, was significantly higher in the
      LDL3 subfraction (33.1 +/- 4.8 and 53.4 +/- 11.5 respectively) than in the LDL2
      (18.6 +/- 5.3 and 26.8 +/- 10.4 respectively, P < 0.0001 for both comparisons)
      and LDL1 subfractions (5.1 +/- 1.5 and 7.8 +/- 2.6, respectively, P < 0.0001 for
      both comparisons). Additionally, the enzyme activity in each LDL subfraction of
      the heterozygous FH patients was significantly higher than in control subjects (P
      < 0.02 for LDL1, P < 0.03 for LDL2 and P < 0.0001 for LDL3). No difference was
      observed in the susceptibility to oxidation of each LDL subfraction among the
      heterozygous FH patients and the normolipidaemic control subjects. During
      oxidation, the PAF-AH activity decreased, whereas the lyso-PC levels
      significantly increased in all subfractions of both groups. The lyso
      PC/sphingomyelin molar ratio in each LDL subfraction of the FH patients 3 h after
      the onset of the oxidation was significantly higher than in control subjects
      [0.38 +/- 0.05 and 0.27 +/- 0.04, respectively, for LDL1 (P < 0.006), 0.47 +/-
      0.08 and 0.39 +/- 0.03, respectively, for LDL2 (P < 0.04), 0.55 +/- 0.11 and 0.42
      +/- 0.06, respectively, for LDL3 (P < 0.02)]. Our results show that heterozygous
      FH patients exhibit higher PAF-AH activity than control subjects in all LDL
      subfractions, resulting in higher lyso-PC production during oxidation, which
      confers on these subfractions higher biological potency. This phenomenon, in
      combination with the diminished anti-atherogenic and antioxidant capability of
      HDL in these patients due to the relatively low HDL-cholesterol levels compared
      with LDL-cholesterol levels and, consequently, the relatively low HDL-associated
      PAF-AH activity, could contribute to the higher atherogenicity and incidence of
      coronary artery disease observed in FH patients.

PMID- 9263750
TI  - Circulating anti-(xanthine oxidoreductase) antibodies in healthy human adults.
AB  - Levels of free anti-(xanthine oxidoreductase) (XOR) antibodies in the serum of
      normal healthy human subjects were determined, using both human and bovine enzyme
      as antigen, in an enzyme-linked immunosorbent assay (ELISA). Levels of IgM class
      anti-(human XOR) antibodies were found to be particularly high (mean values
      representing approximately 3% of total IgM) and to be significantly higher than
      levels of IgM anti-(bovine XOR) antibodies, indicating that endogenous XOR,
      rather than ingested bovine milk XOR, is the immunogen. IgM anti-XOR antibody
      levels were significantly higher in women under 50 years than in age-matched men,
      or in older women. Levels of IgG class anti-XOR antibodies were much lower and
      showed no correlation with gender or age. Affinity-purified anti-(human XOR)
      antibodies only partially inhibited enzymic activities of XOR. The majority of
      both IgM and IgG anti-(human XOR) antibodies in serum occurred as immune
      complexes, suggesting that the specific antibodies have a protective role in
      removing potentially damaging XOR from the circulation.

PMID- 9263751
TI  - Differentiation of BCS-TC2 human colon adenocarcinoma cells by sodium butyrate:
      increase in 5'-nucleotidase activity.
AB  - We have analysed the major effects of sodium butyrate on the morphology, protein
      content and induction of epithelial differentiation markers in human colon
      adenocarcinoma BCS-TC2 cells. Sodium butyrate alters the cell morphology,
      inducing a larger cellular size, flattening and vacuolization. The protein
      content per cell increases, whereas the proliferation rate is reduced. Moreover,
      cell death by apoptosis is also observed. Butyrate-treated cells show higher
      levels of alkaline phosphatase activity and carcinoembryonic antigen, suggesting
      that this agent induces the in vitro differentiation of BCS-TC2 cells. These
      effects are reversible and time and dose dependent. In addition, we have observed
      that the ectoenzyme 5'-nucleotidase activity also increases during this
      treatment, suggesting that it could be considered as a new differentiation marker
      for this type of carcinoma cells. These results contribute to the understanding
      of the action of sodium butyrate as a potential cancer chemotherapeutic agent.

PMID- 9263752
TI  - No effect of calcitriol on insulin-mediated glucose uptake in healthy subjects.
AB  - Administration of active vitamin D (calcitriol) improves insulin sensitivity in
      uraemic patients. These patients have subnormal plasma calcitriol concentrations
      in parallel with increased intact parathyroid hormone (PTH) concentrations. It is
      therefore unclear whether the improvement in insulin sensitivity results from a
      direct effect of calcitriol or from amelioration of secondary
      hyperparathyroidism. So far, no evidence has been presented that insulin
      sensitivity is specifically affected by calcitriol in healthy subjects. We
      investigated the effect of (supra)therapeutic doses of calcitriol on insulin
      sensitivity in healthy volunteers. In a double-blind parallel group design, 18
      healthy male subjects received in random order either placebo or 1.5 micrograms
      of calcitriol per day by mouth for 7 days. Insulin-mediated glucose uptake, i.e.
      insulin sensitivity, was assessed using the euglycaemic clamp technique. Mean
      glucose disposal rate, i.e. M-value, was not significantly affected by placebo or
      calcitriol treatment (placebo: 7.1 +/- 1.3 mg kg-1 min-1 before and 7.2 +/- 1.5
      mg kg-1 min-1 after treatment; calcitriol 7.0 +/- 1.4 mg kg-1 min-1 and 7.2 +/-
      1.4 mg kg-1 min-1). There were no significant changes in mean plasma glucose,
      insulin, phosphate, bicarbonate and ionized calcium concentrations after
      administration of placebo or calcitriol. Furthermore, platelet intracellular
      calcium concentration (assessed by fluorescence spectroscopy) and mean arterial
      blood pressure (24 h ambulatory measurement) did not change with placebo and
      calcitriol treatment. On the other hand, mean intact PTH concentration decreased
      significantly (P < 0.01) with calcitriol treatment, but not with placebo. In
      addition, mean 24 h urinary calcium excretion increased significantly (P < 0.05)
      with calcitriol administration but was unchanged with placebo. Administration of
      (supra)physiological doses of calcitriol has no effect on insulin sensitivity in
      healthy subjects, despite a significant decrease in PTH concentrations. These
      observations are compatible with the notion that the effect of calcitriol on
      insulin sensitivity is present only in uraemic calcitriol-depleted patients.

PMID- 9263753
TI  - Reciprocal association between insulin sensitivity and the haematocrit in man.
AB  - In epidemiological studies, a high haematocrit has been associated both with
      increased cardiovascular risk and with hyperinsulinaemia, a surrogate of insulin
      resistance. To examine directly the relationship between the haematocrit and
      insulin sensitivity, we studied 12 healthy volunteers and 12 patients with non
      insulin-dependent diabetes mellitus (NIDDM) with the use of a 4-hour
      hyperinsulinaemic [1 mU min-1 kg-1] isoglycaemic clamp. In the whole group,
      insulin sensitivity (as the ratio of insulin-mediated glucose clearance to steady
      state plasma insulin concentrations) was inversely related to the haematocrit (r
      = 0.50, P < 0.01). To test whether acute changes in the haematocrit affect
      insulin sensitivity, in two NIDDM patients and three healthy subjects the clamp
      study was repeated after lowering (-18%) the haematocrit by erythro-apheresis. In
      all five subjects, the lower haematocrit was associated with slightly reduced (
      7% on average, P = NS) rather than increased insulin sensitivity. We conclude
      that insulin sensitivity is inversely related to the haematocrit independently of
      the glucose tolerance status. The association does not result from acute
      haemodynamic effects on insulin sensitivity, and may therefore reflect an action
      of insulin resistance/ hyperinsulinaemia on blood viscosity, or the presence of a
      common determinant.

PMID- 9263754
TI  - Calretinin is transiently expressed in tendon fibroblasts of the paravertebral
      region of the chick embryo.
AB  - Although calretinin is an intracellular calcium acceptor protein essentially
      located in neurons, we have previously shown that calretinin was also expressed
      in the mesenchymal cells forming the intervertebral disc. Here, we describe,
      using immunohistochemistry, the transient expression of calretinin in fibroblasts
      responsible for the tendon formation in the paravertebral region. We have looked
      at chick embryos from embryonic day 4 to day 18. At embryonic day 6, calretinin
      immunoreactivity was detected in chick embryo cells located laterally to the
      spinal cord between two groups of developing muscular cells. At embryonic day 8,
      calretinin immunoreactivity intensity was the highest in cells showing a
      fibroblast morphology. After embryonic day 8, when fibroblast proliferation
      decreased and differentiation increased, calretinin immunoreactivity
      progressively disappeared. Interestingly, calretinin could not be detected in
      fibroblasts of the anterior and posterior limbs at any investigated age. Because
      calretinin expression appeared selectively and transiently in the fibroblasts of
      the paravertebral region, we may conclude that the phenotype of those fibroblasts
      is different from the limbs fibroblasts.

PMID- 9263755
TI  - A comparative review of the sites of histoenzymatic dephosphorylating activities
      and of gene expression in developing limb buds of mammalian and avian species.
AB  - The sites of dephosphorylating activities histochemically demonstrated in
      developing limb buds of mammalian and avian species have been reviewed and
      compared with the pattern of gene expression or of other biochemical properties
      reported at similar stages in the corresponding sites. Alkaline phosphatase, acid
      phosphatase, 5' nucleotidase and ATP-phosphohydrolase reactions were studied in
      mouse, rat and chick embryos. Alkaline phosphatase only was detected in mole limb
      buds whereas only 5' nucleotidase and ATP-phosphohydrolase were revealed in limb
      rudiments of macacus rhesus embryos. Five decisive periods or events of limb
      morphogenesis have been considered successively: (1) the early stages during
      which the prospective limb constituents acquire limb forming properties and give
      rise to the young limb buds, (2) the invasion of the limb bud mesoderm by
      myogenic cells of somitic origin, (3) the ectoderm-mesoderm interactions with
      particular emphasis on the properties displayed by the apical ectodermal ridge
      and by the underlying subridge mesoderm of the progress zone, (4) the period of
      growth and pattern formation along the proximo-distal, anterior-posterior and
      dorso-ventral axes, with special attention to the properties of the zone of
      polarizing activity, and (5) the period of tissular predifferentiation
      particularly as concerns prospective skeletal, musculo-tendinous and connective
      tissues, with brief comments about growing nerves and blood vessels. At least
      during the morphogenetic period, most dephosphorylating properties appear
      independently associated with gene expression or other regional biochemical
      properties. Many sites of dephosphorylating activity may therefore be considered
      as interesting markers of ungoing morphogenetic events among which tissue
      interaction and signalling are frequently concerned.

PMID- 9263756
TI  - Presence and function of growth factors in the avian ovary.
AB  - It is now evident that a number of growth factors and cytokines are intimately
      involved in ovarian processes. This review focuses on these autocrine/paracrine
      modulators in terms of describing their presence and function in avian ovaries.

PMID- 9263757
TI  - The cranial lateral-line system in Clarias gariepinus (Burchell, 1822)
      (Siluroidei:Clariidae): morphology and development of canal related bones.
AB  - The cranial lateral-line system, as well as the canal bones are well developed in
      the African clariid catfish Clarias gariepinus. A generalised cranial lateral
      line pattern is present (supraorbital, infraorbital, preoperculo-mandibular,
      otic, postotic and temporal canals). The supratemporal commissure, however, is
      missing, although a supraorbital commissure is present (formed through the fusion
      of the epiphysial branches). In addition to canals, some pit-lines are present
      which cover both canal regions and non-canal regions (vertical, horizontal, oral,
      anterior, middle and posterior pit-lines). In this paper, several ontogenetic
      stages of the canal related bones in C. gariepinus were studied. A description of
      the canal bones, as well as some considerations concerning their nomenclature are
      given. All canal bones develop, whereas the parietal bone seems to have fused
      with the supraoccipital bone during ontogeny, as has been observed in some
      siluroids. The extrascapulars (= supratemporals) are missing in C. gariepinus, as
      is the case in many siluroids. The posttemporal and supracleithral bones have
      fused as well. Surprisingly, some separate splenial bones, enclosing the distal
      part of the mandibular canal are present. Some secondary modifications indicate
      the apomorphic features of the Clariidae. The infraorbital bones, from which the
      antorbital bone has lost the antorbital commissure, and the suprapreopercular
      bone are enlarged, plate-like bones. The nasal bone has undergone some secondary,
      plate-like extensions as well.

PMID- 9263758
TI  - Modulation of the calcium sensitivity of the smooth muscle contractile apparatus:
      molecular mechanisms, pharmacological and pathophysiological implications.
AB  - Smooth muscle contraction is the basis of the physiological reactivity of several
      systems (vascular, respiratory, gastrointestinal, urogenital ...).
      Hyperresponsiveness of smooth muscle may also contribute to a variety of problems
      such as arterial hypertension, asthma and spontaneous abortion. An increase in
      cytoplasmic calcium concentration ([Ca2+]i) is the key event in excitation
      contraction coupling in smooth muscle and the relationship linking the [Ca2+]i
      value to the force of contraction represents the calcium sensitivity of the
      contractile apparatus (CaSCA). Recently, it has become evident that CaSCA can be
      modified upon the action of agonists or drugs as well as in some
      pathophysiological situations. Such modifications induce, at a fixed [Ca2+]i
      value, either an increase (referred to as sensitization) or a decrease
      (desensitization) of the contraction force. The molecular mechanisms underlying
      this modulation are not yet fully elucidated. Nevertheless, recent studies have
      identified sites of regulation of the actomyosin interaction in smooth muscle.
      Sensitization primarily results from the inhibition of myosin light chain
      phosphatase (MLCP) by intracellular messengers such as arachidonic acid or
      protein kinase C. In addition, phosphorylation of thin filament-associated
      proteins, caldesmon and calponin, increases CaSCA. Activation of small
      (monomeric) G-proteins such as rho or ras is also involved. Desensitization
      occurs as a consequence of phosphorylation of myosin light chain kinase (MLCK) by
      the calcium-calmodulin activated protein kinase II, or stimulation of MLCP by
      cyclic GMP-activated protein kinase. In the present review, examples of
      physiological modulation of CaCSA as well as pharmacological and
      pathophysiological implications are illustrated for some smooth muscles.

PMID- 9263759
TI  - Dynamics of the cationic and secretory responses to A-4166 in perifused
      pancreatic islets.
AB  - The dynamics of the cationic and secretory response to A-4166, a hypoglycemic
      meglitinide analogue, was investigated in rat islets prelabelled with either 36Rb
      or 45Ca and placed in a perifusion system. In the absence of D-glucose, A-4166
      (10 microM) provoked an immediate, sustained and rapidly reversible inhibition of
      36Rb outflow, this contrasting with a short-lived stimulation of insulin release.
      In the presence of 6 mM D-glucose, A-4166 provoked a rapid, sustained and rapidly
      reversible stimulation of both insulin release and 45Ca efflux. The latter
      cationic response was suppressed in the absence of extracellular Ca2+, in which
      case A-4166 even caused a modest decrease in effluent radioactivity. These
      findings support the view that A-4166 acts mainly in the islet B-cell by closing
      ATP-responsive K+ channels, leading to subsequent depolarization of the plasma
      membrane and gating of voltage-sensitive Ca2+ channels. Independently of the
      latter effect, A-4166 may also affect the intracellular distribution of Ca2+
      ions. The present data further indicate that A-4166 belongs to those hypoglycemic
      agents that cause rapidly reversible changes in cationic and secretory events, at
      variance with highly potent sulfonylureas such as glibenclamide or glimepiride.

PMID- 9263760
TI  - NG-nitro-L-arginine methyl-ester: a muscarinic receptor antagonist?
AB  - The effect of the nitric oxide synthase inhibitor NG-Nitro-L-arginine methyl
      ester (L-NAME) towards muscarinic receptors was studied in vitro and in vivo. L
      NAME displaced the antimuscarinic ligand [3H]quinuclidinyl benzilate ([3H]QNB)
      from its specific binding sites in rat cerebral cortex and cerebellum homogenates
      with a more than 10,000 fold lower affinity than atropine, pirenzepine and AFDX
      116. Data for L-NAME binding were best fit according to a two-site model (Kd 7.2
      nM and 3,000 nM) in the rat cerebellum, whereas in rat cortex a one-site model
      (Kd 1670 nM) was superior. In anesthetized rats and rabbits L-NAME (7.5-185
      mumol/kg) attenuated a hypotensive response to Acetyl beta-methyl-choline (Ac
      beta-Me Ch)(6.25 nmol/kg) in a dose related fashion, but this effect was
      negligible as compared to that of atropine (8.8 and 17.7 nmol/kg). Furthermore,
      the effect of L-NAME was not specifically antimuscarinic since its attenuating
      effect against ATP- or histamine-induced responses was not statistically
      different from that of Ac beta-Me Ch. A vagus stimulation induced bradycardia was
      entirely uninfluenced by L-NAME (37 mumol/kg). In isolated bladder experiments
      (rabbit) we demonstrated a complete lack of efficacy of L-NAME against Ac beta-Me
      Ch induced contractions. In the pithed rat preparation L-NAME was ineffective
      against the MeN-A-343 induced pressor responses. In summary, we demonstrated that
      the nitric oxide synthase inhibitor L-NAME shows very weak affinity at M1- and M2
      receptors in the rat brain in vitro, but appears to have no significant
      antimuscarinic properties against M1-, M2- and M3-receptor mediated effects in
      rats and rabbits in vivo.

PMID- 9263761
TI  - The effects of ryanodine on calcium uptake by the sarcoplasmic reticulum of
      ischemic and reperfused rat myocardium.
AB  - The effects of ischemia and reperfusion on sarcoplasmic reticulum (SR) calcium
      uptake were measured in crude heart homogenates of rats and were compared to
      published results for rabbit hearts. Isolated rat hearts (n = 5 in each group)
      were Langendorff-perfused at 37 degrees C and were either kept normally perfused
      (control group), or submitted to 15 min normothermic ischemia (ischemic group),
      or reperfused for 10 min after 15 min ischemia (reperfused group). Mechanical
      function recovered to 50-60% of control after 10 min reperfusion following
      ischemia. Ca uptake (control Vmax: 23.0 +/- 2.20 nmol.min.1.mg of protein-1)
      decreased during ischemia (Vmax: 15.7 +/- 1.60 nmol.min-1.mg-1) but recovered to
      control level on reperfusion (Vmax: 20.8 +/- 2.02 nmol.min-1.mg-1). An increased
      Ca uptake was obtained when the measurements were carried out in the presence of
      ryanodine (430 microM) to block Ca leakage through SR Ca-release channels. The
      relative magnitude of ryanodine effect in the ischemic myocardium (increase: 77.2
      +/- 18.20%) was more marked than in control (32.0 +/- 8.22%) or reperfused
      myocardium (39.0 +/- 10.66%). This result is different from that of rabbit
      myocardium where similar ryanodine effect is present in all groups (56.7 +/-
      13.76%, 50.0 +/- 13.56% and 54.2 +/- 6.88% in control, ischemic and reperfused
      hearts, respectively) and suggests that a component of cytosolic Ca overload via
      SR Ca-release channels is present during ischemia in rat, but not in rabbit
      myocardium.

PMID- 9263762
TI  - Coronary effects of exogenous and endogenous bradykinin in conscious dogs.
AB  - The effects of intravenous (iv) bolus administrations of bradykinin (0.1-1
      microgram.kg-1) on large and small coronary arteries were investigated in seven
      chronically instrumented conscious dogs. Bradykinin dose-dependently increased
      heart rate, left ventricular dP/dt max, coronary blood flow and coronary artery
      diameter and decreased aortic pressure. Subchronic inhibition of the nitric oxide
      synthase (NOS) pathway (N omega-nitro-L-arginine, 20 mg.kg-1.d-1 during 7 days)
      attenuated the systemic and coronary effects of bradykinin. HOE 140, a specific
      bradykinin B2 receptor antagonist, administered at a dose (30 micrograms/kg)
      sufficient to completely inhibit the systemic and coronary effects of exogenous
      bradykinin (1 microgram/kg, iv bolus), had no effect on baseline systemic and
      coronary hemodynamic parameters. HOE 140 had also no effect on the flow-dependent
      increase in large coronary artery diameter and on the relationship between flow
      debt and flow repayment volumes observed during myocardial reactive hyperemia.
      This lack of effect of HOE 140 persisted when experiments were repeated after NOS
      inhibition. We conclude that (a) exogenous bradykinin dilates large and small
      coronary arteries through a partially NO-mediated mechanism, and (b) endogenous
      bradykinin plays no role in the control of arterial pressure, heart rate, LV
      dP/dt max, basal and flow-stimulated coronary hemodynamics, both in control
      conditions and after subchronic inhibition of NOS in the conscious dog.

PMID- 9263763
TI  - Chronotropic and inotropic effects of terikalant on isolated, blood-perfused
      atrial and ventricular preparations of dogs.
AB  - We investigated the effects of terikalant, which blocks inward rectifier K+
      current, on the sinus rate, atrial and ventricular contractile force in the
      isolated, blood-perfused right atrial and left ventricular preparations of dogs,
      and the effects of terikalant on the negative cardiac responses to acetylcholine,
      adenosine or pinacidil (an ATP-sensitive K+ channel opener) and on the positive
      cardiac responses to norepinephrine. Terikalant (1-100 nmol) decreased sinus rate
      and briefly and slightly increased atrial contractile force in isolated atria.
      However, terikalant did not increase ventricular contractile force in isolated
      ventricles. Neither propranolol nor atropine inhibited the positive inotropic and
      negative chronotropic responses to terikalant, respectively. Terikalant (10 or 30
      nmol) did not significantly affect the negative cardiac responses to
      acetylcholine, adenosine nor pinacidil and the positive responses to
      norepinephrine. These results suggest that terikalant decreases sinus rate with a
      small changes in myocardial contractile force and does not affect the cardiac
      responses to muscarinic and adenosine receptor agonists, ATP-sensitive K+ channel
      openers nor beta-adrenoceptor agonists in the dog heart.

PMID- 9263764
TI  - alpha-Methylnoradrenaline-induced contractions in rat aorta are mediated via
      alpha 1D-adrenoceptors.
AB  - The subtype(t) of alpha-adrenoceptor-mediating contractions to alpha
      methynoradrenaline in the rat aorta has been investigated by using alpha
      adrenoceptor-selective competitive antagonists and the alpha 1-adrenoceptor
      selective agonist, phenylephrine, for comparison. alpha-Methylnoradrenaline and
      phenylephrine elicited concentration-dependent contractions in the endothelium
      denuded and endothelium-intact aortic rings with similar potencies and maximal
      effects. alpha-Methylnoradrenaline- and phenylephrine-induced contractions in
      endothelium-denuded aortic rings were competitively antagonized by prazosin (pA2
      = 9.38 and 9.13; respectively) and rauwolscine (pA2 = 7.19 and 6.60,
      respectively). This confirms that there is an alpha 1- and a non alpha 2
      adrenoceptor response to alpha-methylnoradrenaline in the rat aorta. The subtype
      selective alpha 1D-adrenoceptor antagonist, BMY 7378, was found to antagonize
      contractions to alpha-methylnoradrenaline and phenylephrine competitively in
      endothelium-denuded and endothelium-intact aortic rings. The pA2 values of BMY
      7378 against alpha-methylnoradrenaline (8.39 and 8.41; endothelium-intact and
      endothelium-denuded, respectively) and phenylephrine (8.64 and 8.76; endothelium
      intact and endothelium-denuded, respectively), are consistent with its published
      functional potency and clonal alpha 1D-adrenoceptor binding affinity. In
      addition, contractions to alpha-methylnoradrenaline and phenylephrine in
      endothelium-denuded aortic rings, were potently inhibited by WB 4101 with pA2
      values of 9.75 and 9.25, respectively. The high pA2 values for WB 4101 indicate
      that the alpha 1B-adrenoceptor subtype does not seem to participate in alpha
      methylnoradrenaline (and phenylephrine) induced contractions in this artery.
      These results suggest that the alpha 1D-subtype plays a determining role in rat
      aorta contractions induced by alpha-methylnoradrenaline.

PMID- 9263765
TI  - Quantitative opioid withdrawal signs in rats: effects exerted by clothiapine
      administration.
AB  - An opioid withdrawal syndrome, which causes alteration of several physiological
      signs, was induced in rats by repeated morphine administration and final naloxone
      injection. The aim of this study was prevention of the altered physiological
      profiles by utilising clothiapine, which is capable of affecting fecal and
      urinary excretion, rectal temperature, pain threshold levels and salivatory
      behaviour. Morphine was administered in three daily intraperitoneal (ip)
      injections for 4 days at doses of 9, 16 and 25 mg/kg (d 1), 25, 25 and 50 mg/kg
      (d 2), 50, 50 and 50 mg/kg (d 3) and 50, 50 and 100 mg/kg (d 4). Naloxone was
      injected (30 mg/kg) ip 180 min after the last morphine injection. Clothiapine was
      administered orally 0.7, 2 and 6 mg/kg 2 hours before the naloxone
      administration. Signs such as fecal and urine excretion, rectal temperature and
      latency times to thermal stimulus salivation, jumping and wet dog shakes were
      affected in different ways by morphine, naloxone, clothiapine and combination of
      them. Notably the administration of clothiapine in rats receiving morphine and
      naloxone decreased the intensity of certain withdrawal symptoms, such as altered
      excretion of feces, temperature values, salivation, jumping and wet dog shakes
      behaviour, and elevated the nociceptive threshold values. The effects exhibited
      by clothiapine administration may be explained through its antimuscarinic,
      antiadrenergic and antidopaminergic activities interfering with the mechanisms
      involved in the regulation of these previously mentioned withdrawal symptoms. The
      use of this drug is thus suggested as a possible control of the acute phase of
      opioid withdrawal in heroin addicts.

PMID- 9263766
TI  - Effect of MET-88, a gamma-butyrobetaine hydroxylase inhibitor, on myocardial
      derangements induced by hydrogen peroxide in the isolated perfused rat heart.
AB  - The effect of MET-88 (3-(2,2,2-trimethylhydrazinium) propionate dihydrate), a
      gamma-butyrobetaine (gamma-BB) hydroxylase inhibitor, on the hydrogen peroxide
      (H2O2)-induced mechanical and metabolic derangements was studied in the isolated
      rat heart, which was perfused aerobically by the Langendorff's technique at a
      constant flow rate and driven electrically. In the first series of experiments,
      MET-88 (100 mg/kg/d) was orally administered to rats for 10 days prior to
      isolation of the heart. In the second series of experiments, MET-88 or gamma-BB
      was directly infused to the isolated perfused heart. In both series of
      experiments, H2O2 (600 microM) decreased the left ventricular developed pressure
      (mechanical dysfunction) and the tissue levels of high-energy phosphates
      (metabolic derangement). In the first series of experiments, oral pretreatment
      with MET-88 attenuated the H2O2-induced metabolic derangement with a marked
      increase in the myocardial level of gamma-BB, while it did not attenuate the H2O2
      induced mechanical dysfunction. In the second series of experiments, MET-88 (1
      mM) did not attenuate the H2O2-induced metabolic derangement, whereas gamma-BB
      (500 microM or 1 mM) attenuated it. Nevertheless, gamma-BB did not modify the
      energy metabolism of H2O2-untreated heart (normal heart). These results suggest
      that oral pretreatment with MET-88 protects the energy metabolism against the
      H2O2-induced derangement and that the beneficial effect of the oral pretreatment
      with MET-88 may be mediated by gamma-BB that has accumulated in the myocardium
      because of inhibition of gamma-BB hydroxylase.

PMID- 9263767
TI  - Serum bupivacaine concentrations and transplacental transfer following repeated
      epidural administrations in term parturients during labour.
AB  - Bupivacaine is the most widely used local anaesthetic in obstetrics for epidural
      analgesia. Nineteen women (mean age 26.9 +/- 5.3 years) who underwent epidural
      analgesia during labour were included in this study. All parturients received a
      first injection of 21.8 +/- 2.5 mg 0.25% plain bupivacaine. The following
      administrations were given on request: 0.25% concentration was used when cervix
      uteri was supple, and a 0.375% concentration when it was tonic. Blood samples
      were collected 5 min after the first injection and then every 30 min until
      delivery. At delivery blood samples were collected from the infant umbilical cord
      vein and from the arm vein of the mother. Bupivacaine was assayed by high
      pressure liquid chromatography. Serum data were analyzed for each patient using a
      non-compartmental model. Bupivacaine was rapidly detected in serum, and maximal
      concentration was reached between 5 and 35 min. Pharmacokinetic parameters were
      estimated in 17 women after the first injection: 87 +/- 35 min for elimination
      half-life, 60 +/- 19 L for apparent volume of distribution and 0.5 +/- 0.3 L/min
      for plasmatic clearance. For a mean total duration of labour and total dose
      administered of respectively 222 +/- 115 min and 57.1 +/- 28.7 mg the mean value
      of the foeto-maternal ratio was 0.29 +/- 0.10. The infant maximal serum
      concentration was 0.26 microgram/mL. No side effects were spontaneously reported
      by the parturients and all infants had an Apgar score of 10 at 5 min after the
      delivery. We confirm the fast systemic absorption and rapid elimination of
      bupivacaine which may be used without risk of acute toxicity both in mother and
      child, even when it is used in a 0.375% concentration.

PMID- 9263768
TI  - The influence of pregnancy on endothelium-derived nitric oxide mediated
      relaxations in isolated human resistance vessels.
AB  - Pregnancy is associated with drastic hemodynamic adaptations, including a
      decrease in peripheral resistance. Vascular resistance is substantially
      influenced by endothelium-derived nitric oxide (NO). This study was designed to
      investigate whether pregnancy might influence endothelium-derived NO-mediated
      relaxations in human resistance arteries. Reactivity of isolated human
      subcutaneous arteries, dissected out of abdominal fat from women who underwent a
      laparotomy or cesarean section, was studied using a small vessel myograph.
      Addition of acetylcholine (1 nM-10 microM) or bradykinin (1 nM-10 microM) to
      precontracted preparations elicited concentration-dependent relaxation responses
      that were dependent on the presence of the endothelium and were partially
      inhibited by the NO-synthase inhibitor nitro-L-arginine (0.1 mM). The relaxations
      to acetylcholine and bradykinin were similar in vessels isolated from pregnant
      and non-pregnant women. Nitro-L-arginine (0.1 mM) had no influence on basal tone
      and had a similar inhibitory influence on the endothelium-mediated relaxations in
      vessels from non-pregnant and pregnant women. These results indicate that the
      influence of endothelium-derived NO in human subcutaneous resistance arteries is
      not altered at the end of pregnancy.

PMID- 9263769
TI  - Serum butyrylcholinesterase (CHE1) polymorphism in a Chilean population of mixed
      ancestry.
AB  - We estimated the allele frequencies of three variants of serum butyryl
      cholinesterase, CHE1*U, CHE1*A and CHE1*F in an urban population of Santiago,
      Chile, resulting from a mixture of Amerindians with Europeans (mostly Spanish).
      The CHE1*A frequency was approximately that expected for this population but the
      incidence of CHE1*F was higher than previous studies would have predicted,
      probably because in this case more precise techniques were used for its
      detection. The finding of a CHE1 AK individual suggests that allele CHE1*K is
      also present at an appreciable frequency in this population.

PMID- 9263770
TI  - ACP and PGM1 polymorphisms in a Chilean population.
AB  - A random sample of 140 individuals from the population of Valparaiso, Chile, was
      studied for 2 polymorphic genetic markers. The gene frequency estimates were:
      ACP*A = 0.246 +/- 0.026 and PGM1*2 = 0.235 +/- 0.025. The comparison of ACP with
      data obtained from other populations indicates a similarity with Mongoloid groups
      whereas for PGM1, the comparison with the data obtained shows no significant
      difference from Caucasoid populations. These results indicate that the Valparaiso
      population is the result of genetic admixture of various populations.

PMID- 9263771
TI  - Blood group polymorphisms in the Canary Islands.
AB  - Human samples from the seven Canary Islands were studied for the following
      polymorphic red cell blood group systems: ABO, RH, MNSs, FY and P. In contrast to
      the intra-insular homogeneity found, inter-insular heterogeneity was observed for
      ABO, RH and FY. The observed blood group allelic systems were within the range of
      European populations, with some minor African contribution.

PMID- 9263772
TI  - Distribution of glutathione S-transferase T1 phenotypes in the Estonian
      population.
AB  - The distribution of glutathione S-transferase T1 (GSTT1) phenotypes was studied
      in a total sample of 673 Estonians whose four grandparents were born in Estonia,
      by an ELISA test able to differentiate between GSTT1 positive and GSTT1 negative
      phenotypes. 18% of the total sample did not present GSTT1-1 protein in whole
      blood. GSTT1-1 concentration was assayed in 519 out of the 552 GSTT1 positive
      subjects (i.e. 82% of the total sample) 49% percent of this subsample made up by
      519 subjects was found to have GSTT1-1 in intermediate concentration and 33% in
      high concentration. The gene frequency of the GSTT1 deleted allele was estimated
      to be 0.423 as the square root of the frequency of the GSTT1 negative subjects
      (square root of 0.18 = 0.423) and that of the GSTT1 positive allele as (1-0.423)
      = 0.577. Statistically significant regional differences were found within the
      population with the lowest frequency of GSTT1 negative in western Estonia (9.5%)
      and the highest in the southeastern part of the country (24.5%).

PMID- 9263773
TI  - Hemogenetic studies in southern Germany.
AB  - Typing of 23 blood groups, serum protein and red cell enzyme polymorphism was
      performed on two samples from Baden-Wurttemberg, Germany. One random sample comes
      from the city of Ulm and its surroundings and the other from a small isolate
      located in Upper Swabia. While the Ulm sample displayed allele and haplotype
      frequencies similar to those of other German populations, the sample from the
      isolate turned out to be different.

PMID- 9263774
TI  - Distribution of AB0 and Lewis blood groups in Greece.
AB  - The distribution of AB0 blood and Lewis blood group phenotypes in 2988 Greek
      individuals was determined with monoclonal reagents and the results analysed
      according to their birthplace or that of their parents when they were born in the
      same region. Overall, the AB0 blood groups distribution was similar to that
      reported for Greek soldiers in 1919. The only unusual variation was that 29% of
      the donors born in Thrace were group B. The proportion of Lewis (a-b-)
      individuals ranged from 1-3%. The frequency of Le (a+b-) donors (non-secretors)
      ranged from 16% in Thessaly to 27% in East Macedonia, Epirus and those born
      abroad; the Le (a-b+) frequency was 71-83%.

PMID- 9263775
TI  - HLA gene frequencies and migration in an Italian province.
AB  - HLA class I (HLA-A, HLA-B) and class II (HLA-DR, HLA-DQ) gene frequencies in 6
      subareas of Pavia province are calculated in two samples of bone marrow donors.
      We estimated the degree of genetic differentiation between the 6 sub-areas
      through the standardized variance FST. On the basis of the island migration model
      the number of migrants is estimated from FST and compared with the observed
      migration index in the province according to the 1991 census.

PMID- 9263776
TI  - Cystic Fibrosis in Ukraine: age, origin and tracing of the delta F508 mutation.
AB  - Seven already known CF mutations were searched in 170 unrelated cystic fibrosis
      patients from different regions of Ukraine. Their frequencies in this sample
      were: delta F508-50%, 1677delTA-0.3% (10th exon), R553X-0.6%, G551D-0.3% (11th
      exon), R334W-0.6% (7th exon). 1154insTC (7th exon) and S549I (11th exon) were not
      found. Heterozygotes for delta F508 were searched in 865 healthy volunteers from
      different Ukranian regions. Their frequencies ranged from 1:28 to 1:70. We report
      here unpublished population data from Ukraine in order to discuss the origin,
      evolution and dispersion of chromosomes bearing the delta F508 mutation.
      Selection in terms of heterozygote advantage is also discussed.

PMID- 9263777
TI  - Present and future of intraoperative radiation therapy (IORT). Keynote address.

PMID- 9263778
TI  - Quality of life and cancer IORT treatment. del Regato Distinguished Lecture.

PMID- 9263779
TI  - Intraoperative radiation therapy terminology.

PMID- 9263780
TI  - Combining intraoperative and conventional external radiotherapy doses: a biology
      based approach.

PMID- 9263781
TI  - Implications of vasomotor reactions for a combined oncotherapy including IORT. I.
      Angiophysiology and oncotherapy.

PMID- 9263782
TI  - Implications of vasomotor reactions for a combined oncotherapy including IORT.
      II. Possibilities for adjuvant pharmacotherapy in oncotherapy.

PMID- 9263783
TI  - Implications of vasomotor reactions for a combined oncotherapy including IORT.
      III. On cell-physiological mechanisms in oncotherapy.

PMID- 9263784
TI  - Experimental study of vascular sequelae of combined upper abdominal
      intraoperative and external-beam radiation therapy.

PMID- 9263785
TI  - Late effects of integrated therapies, including IORT, on lumbosacral plexus and
      anorectal physiology in patients treated for rectal cancer.

PMID- 9263786
TI  - Tissue changes in normal canine liver following intraoperative brachytherapy.

PMID- 9263787
TI  - Reactions of the gastric wall following IORT +/- ERT to the upper abdomen in
      rabbits.

PMID- 9263788
TI  - 3-D dose reconstruction in IORT.

PMID- 9263789
TI  - IORT Novac7: a new linear accelerator for electron beam therapy.

PMID- 9263790
TI  - Preliminary studies for clinical applications of Novac7, a robotic mobile
      intraoperative electron beam therapy unit.

PMID- 9263791
TI  - The Mobetron: a new concept for IORT.

PMID- 9263792
TI  - Field shaping in IORT.

PMID- 9263794
TI  - IORT in P.A. Ghertsen Oncological Institute: reality and perspectives.

PMID- 9263793
TI  - Early IORT experience in a public university hospital in Spain: Hospital General
      Universitario Gregorio Maranon (Madrid).

PMID- 9263795
TI  - IORT in a Lithuanian Oncology Center.

PMID- 9263796
TI  - Malignant brain tumors treated with IORT.

PMID- 9263797
TI  - Clinical study of glioma treated with HDR Ir-192 interstitial brachytherapy and
      surgical resection.

PMID- 9263799
TI  - A new method for treatment planning and quality control in IORT of brain tumors.

PMID- 9263798
TI  - IORT for malignant brain tumors.

PMID- 9263800
TI  - IORT in floor of the mouth cancer.

PMID- 9263801
TI  - Adjuvant electron-beam IORT in high-risk head and neck cancer patients.

PMID- 9263802
TI  - IORT using electron beam or HDR brachytherapy for previously unirradiated head
      and neck cancers.

PMID- 9263803
TI  - IORT for locally advanced oropharyngeal carcinomas with major extension to the
      base of the tongue: 5-year results of a prospective study.

PMID- 9263804
TI  - IORT in the management of locally advanced or recurrent head and neck cancer.

PMID- 9263805
TI  - IORT for early breast cancer: a report on long-term results.

PMID- 9263806
TI  - IORT in breast carcinomas.

PMID- 9263807
TI  - IORT for non-small-cell lung cancer: preliminary report of 33 cases.

PMID- 9263808
TI  - Resection and IORT followed by three-dimensional conformal radiotherapy with or
      without adjuvant chemotherapy for malignant mesothelioma.

PMID- 9263809
TI  - IORT for extremity sarcomas.

PMID- 9263810
TI  - IORT in the management of extremity and limb girdle soft tissue sarcomas.

PMID- 9263811
TI  - Intraoperative high-dose-rate brachytherapy after preoperative radiochemotherapy
      in the treatment of Ewing's sarcoma.

PMID- 9263812
TI  - Early results of IORT in the treatment of gastric cancer.

PMID- 9263813
TI  - IORT in gastric carcinoma: the Lyon experience. A retrospective series of 63
      patients.

PMID- 9263814
TI  - IORT combined with resection for stage IV gallbladder carcinoma.

PMID- 9263815
TI  - IORT of carcinoma of the extrahepatic bile ducts.

PMID- 9263816
TI  - Dose-volume histogram analysis of external-beam irradiation combined with IORT
      for unresectable pancreatic cancer.

PMID- 9263817
TI  - IORT in pancreatic adenocarcinoma.

PMID- 9263818
TI  - IORT for pancreatic cancer: the Kyoto University experience.

PMID- 9263819
TI  - CT changes following IORT for unresectable pancreatic cancer.

PMID- 9263820
TI  - IORT in primary rectal cancer (T3-4Nx): multi-institutional experience with
      conventional treatment sequence. Spanish Group of IORT.

PMID- 9263821
TI  - Intense local therapy in primary rectal cancer: multi-institutional results with
      preoperative chemo-radiation therapy plus IORT. Spanish Group of IORT.

PMID- 9263822
TI  - IORT as adjuvant treatment in primary rectal carcinomas: multi-modality
      treatment.

PMID- 9263823
TI  - Locally advanced primary colorectal cancer: IOERT and EBRT +/-5-FU.

PMID- 9263824
TI  - IORT in integrated treatment of high-risk rectal cancers.

PMID- 9263825
TI  - Chemoradiation therapy and IORT in locally advanced rectal cancer: preliminary
      results in 36 patients.

PMID- 9263826
TI  - IORT: a randomized trial in primary rectal cancer by the French group of IORT.

PMID- 9263827
TI  - Combined modality treatment including IORT in locally advanced and recurrent
      rectal cancer: results from a prospective Norwegian study.

PMID- 9263828
TI  - Locally recurrent colorectal cancer: IOERT and EBRT +/-5-FU and maximal
      resection.

PMID- 9263830
TI  - IORT as a surgical adjuvant for pelvic recurrence of rectal cancer.

PMID- 9263829
TI  - IORT for recurrent rectal carcinoma.

PMID- 9263831
TI  - IORT using high-dose-rate brachytherapy or electron beam for colorectal
      carcinoma.

PMID- 9263832
TI  - Pathological downstaging does not guide the need for IORT in primary locally
      advanced rectal cancer.

PMID- 9263833
TI  - Report on radiotherapy for bladder cancer during surgery.

PMID- 9263834
TI  - Pilot study of IORT for bladder carcinoma.

PMID- 9263835
TI  - IORT for locally advanced or recurrent renal cell carcinoma.

PMID- 9263836
TI  - IORT for locally advanced gynecological malignancies.

PMID- 9263837
TI  - The role of IORT as salvage therapy for recurrent cervical and endometrial
      carcinoma.

PMID- 9263838
TI  - Tumor debulking and IORT for recurrent gynecological carcinomas of the pelvic
      sidewall.

PMID- 9263839
TI  - Prognostic factors for local control in recurrent cervical carcinoma treated with
      IORT: report of the French IORT Group.

PMID- 9263840
TI  - Experimental infection of non-pregnant and pregnant sheep with Neospora caninum.
AB  - In an initial experiment, 21 sheep in groups of five or six were inoculated
      subcutaneously (sc) with 10(8), 10(6) or 10(4) Neospora caninum tachyzoites
      (Liverpool isolate), or with control inoculum, and monitored for clinical signs
      and for "seroconversion". Animals given the two higher doses showed febrile
      responses and all three groups inoculated with the parasite showed
      seroconversion. In a second experiment, 12 pregnant sheep were each inoculated sc
      at 90 days' gestation with 10(6) tachyzoites, and at 25, 40 and 53 days post
      inoculation (dpi) groups of four were killed for examination of the fetuses and
      placentas. Appropriate control ewes were included in the study. All fetuses were
      alive immediately before their dams were killed, except for one, which was found
      to be mummified at 40 dpi. Histopathological lesions were found consistently in
      both fetal central nervous system (CNS) and placental tissues. In the latter,
      focal necrosis, which was mild at 25 dpi, was much more severe at 40 dpi and much
      less severe at 53 dpi. Lesions in the fetal CNS consisted of focal microgliosis
      (with or without central necrosis), lymphoid cuffing and non-suppurative
      meningitis. Lesions were also found in fetal liver, heart and lung. Neospora
      antigen was demonstrated in fetal brain and placental tissues and, at 25 dpi, in
      single samples of fetal liver and heart. The prescapular lymph nodes did not
      differ in size from those of control fetuses but were more mature in that they
      contained a significantly greater number of secondary follicles. Both IgM and IgG
      antibodies to N. caninum were detected in the serum of fetuses from infected
      ewes. Thus, N. caninum readily infected pregnant ewes and caused lesions in fetal
      tissues and placentas which resembled those of ovine toxoplasmosis. In addition,
      the changes were similar to those of bovine neosporosis; the infected pregnant
      ewe therefore offers a good model for the bovine disease.

PMID- 9263841
TI  - Neuronal ceroid-lipofuscinosis in a domestic cat: clinical, morphological and
      immunohistochemical findings.
AB  - A 9-month-old domestic shorthair cat was humanely killed because of uncoordinated
      gait, myoclonus, seizures and reduced vision. Histological, immunohistochemical
      and ultrastructural examination revealed a neuronal storage disease consistent
      with neuronal ceroid-lipofuscinosis (NCL). Neurons contained Sudan black- and
      luxol fast blue-positive material which was autofluorescent.
      Immunohistochemically, the storage material was found to contain subunit c of
      mitochondrial ATP synthase, a protein recently recognized as the main component
      of the storage material in NCL. Ultrastructurally, the material consisted of
      curvilinear and fingerprint bodies, which are indicative of NCL.

PMID- 9263842
TI  - Immunohistopathological characterization of pig pneumonia caused by a combined
      Aujeszky's disease virus and Actinobacillus pleuropneumoniae infection.
AB  - Nine pigs were inoculated endobronchially with Actinobacillus pleuropneumoniae
      serotype 1 (App-1) 6 days after infection with Aujeszky's disease virus (ADV);
      four died within 3 days and the remainder were killed after 1-6 days.
      Immunohistopathologically, there were two types of pneumonic lesion:
      pleuropneumonia, characterized by coagulative necrosis, oedema and fibrinous
      thrombosis; and necrotizing interstitial pneumonia, characterized by bronchitis,
      bronchiolitis and alveolitis. The former type of lesion was associated with App-1
      antigen, and the latter with ADV antigen. These results indicated that a combined
      ADV and App-1 infection produced severe haemorrhagic pleuropneumonia; and that
      ADV and App-1 each produced a characteristic pneumonic lesion.

PMID- 9263843
TI  - Cytohistological and immunological classification of canine malignant lymphomas:
      comparison with human non-Hodgkin's lymphomas.
AB  - Non-Hodgkin's lymphomas (NHLs) in man are on the increase. They are also common
      in dogs, which, as close companions of man, may constitute a useful experimental
      model. However, comparisons cannot be made without a reliable morphological and
      immunological classification of canine NHL. Canine NHLs (n = 134) were classified
      on the basis of fine-needle lymph-node aspirates according to the Kiel
      classification, and 92 were re-classified according to the Working Formulation
      and the updated Kiel classification, in a histological and immunological study.
      The immunophenotype was determined (1) in 92 cases by the use of the pan-T anti
      CD3 polyclonal antibody and the pan-B anti-mb1 monoclonal antibody on paraffin
      wax-embedded tissue sections, and (2) in 47 cases by the use of a panel of
      polyclonal and monoclonal antibodies on fresh preparations and frozen tissue.
      Cytological analysis showed a predominance of high-grade lymphomas (73.9%) over
      low-grade lymphomas (26.1%); it also demonstrated forms not reported in other
      species (small-cell variants, lymphomas with macronucleolated medium-sized cells
      [MMCs], and polymorphic lymphomas with a centroblastic component). Histological
      examination revealed the rarity of follicular lymphomas (2.2% of cases), an
      appearance suggestive of T-cell neoplasia (8.7% of cases), and evidence that some
      MMC lymphomas originated in the marginal perifollicular zones. Some (26%) of the
      lymphomas were of the T-cell phenotype: the majority of these consisted of small
      cell, low-grade lymphomas and mycosis fungoides, the rest being either high-grade
      pleomorphic lymphomas (mixed or large-cell) or, rarely, high-grade, small
      noncleaved-cell, plasmacytoid lymphomas. No lymphoma expressed a double (T and B)
      phenotype. This study revealed similarities with, but also notable differences
      from, human NHL. In particular, the MMC lymphomas may constitute an interesting
      equivalent of human marginal zone B-cell lymphomas.

PMID- 9263844
TI  - Growth fractions in canine non-Hodgkin's lymphomas as determined in situ by the
      expression of the Ki-67 antigen.
AB  - The proportion of proliferating cells in non-Hodgkin's lymphomas (NHLs) as
      determined in situ by the expression of the Ki-67 antigen, has prognostic value
      in human oncology, and is strongly related to the different grades of malignancy.
      The evaluation of the Ki-67 index in canine NHLs may be useful in assessing the
      individual variability of the growth fraction in the different sub-types of
      lymphoma, and also the validity of the classification in terms of grade of
      malignancy. The growth fraction was evaluated in 92 canine NHLs, previously
      classified according to the Kiel classification (as adapted to the canine
      species), by determining the expression of the Ki-67 antigen with the MIB1
      antibody on (1) paraffin-wax tissue sections in all 92 cases, and (2) fine-needle
      aspirates or tumour imprints in 30 cases. The labelling appeared satisfactory in
      88% of the cases, with good concordance between the histological and cytological
      data. A highly significant correlation (P < 0.001) was established between the
      proportion of Ki-67+ cells and the classification into low-grade (Ki-67 index <
      21%) and high-grade malignancy (Ki-67 index > 21% and usually > 29%). In the low
      grade lymphoma group, a macronucleolated medium-sized-cell lymphoma not found in
      man had the lowest proliferation index. In the high-grade malignancy group, the
      number of Ki-67+ cells seemed to be proportional to cell size, whatever the
      phenotype, with the rare exceptions of some unclassifiable small-cell Burkitt
      type or plasmacytoid lymphomas, which were highly proliferating. The
      classification of lymphomas into low-grade and high-grade appears to correlate
      well with their proliferative index. The existence of individual variations,
      within given categories of canine NHL, suggests that, as in human medicine,
      prognosis may be assisted by determining the growth fraction at initial
      diagnosis, and by fine-needle aspiration at relapses.

PMID- 9263845
TI  - Effects of Trypanosoma evansi on the output of cells from a lymph node draining
      the site of Pasteurella haemolytica vaccine administration.
AB  - The prefemoral efferent lymphatics of sheep infected with Trypanosoma evansi and
      inoculated with P. haemolytica vaccine and of those given only the vaccine, were
      surgically cannulated to study the effects of the infection on the total cellular
      output and output of blast cells from the node in response to the vaccine. T.
      evansi delayed and depressed the increases in total cell and lymphoblast outputs.
      In uninfected sheep, the total cellular output increased and peaked at more than
      twice the prevaccination values on days 4 and 5 after primary vaccination, but
      the increases were smaller and peaked on days 6 and 8 after primary vaccination
      in the infected sheep. The output of lymphoblasts mirrored the total cell output,
      though it was suppressed to a greater degree by T. evansi. The output of blasts
      peaked at more than 8 and 14 times the prevaccination values in the uninfected
      animals after primary and secondary (booster) vaccinations, respectively; but in
      infected animals, it peaked at twice the prevaccination values after the primary
      vaccination and showed no increase after booster vaccination until 11 days later.
      It is concluded that the inhibition of total and blast cell outputs by T. evansi
      may limit the early systemic dissemination of antigen-specific cells, thus
      playing a role in the induction of immunosuppression by the parasite.

PMID- 9263846
TI  - Canine cutaneous protothecosis: an immunohistochemical analysis of the
      inflammatory cellular infiltrate.
AB  - In this immunohistochemical study, the distribution of the cellular inflammatory
      infiltrate associated with cutaneous canine protothecosis (Prototheca
      wickerhamii) was evaluated by consecutive biopsies taken before, during and after
      treatment. Antibodies specific to canine immunoglobulins (IgG, IgM, IgA), human
      CD3 antigen (pan T-lymphocyte marker) and human myeloid/ histiocyte antigen
      (macrophage/neutrophil marker) were used. Before treatment, cellular infiltrate
      was very scanty in the inflamed areas, but it increased during the treatment,
      whereas the number of protothecal organisms decreased. Statistical analysis
      revealed an inverse relation between the number of protothecal organisms and the
      number of infiltrating macrophage/neutrophils (P < 0.004), T lymphocytes (P <
      0.001), and cells containing immunoglobulin G (P < 0.001), M (P < 0.001) and A (P
      < 0.001) at different stages of the disease. These findings suggest either that
      protothecal organisms inhibit the migration or proliferation of cellular
      inflammatory infiltrate or that only dead protothecal organisms induce an
      effective local immune response.

PMID- 9263847
TI  - Hypertrophic cardiomyopathy in a common wombat (Vombatus ursinus).
AB  - A case of hypertrophic cardiomyopathy (HCM) in a common wombat (Vombatus ursinus)
      is described. At necropsy, the heart showed symmetrical ventricular hypertrophy,
      a narrow left ventricular cavity, and dilatation of the left atrium.
      Microscopical findings in the ventricular myocardium included a strikingly
      disordered arrangement of cardiac muscle cells, in which adjacent cells were
      aligned perpendicularly and obliquely to each other, interstitial myocardial
      fibrosis, and arteriosclerosis of small intramural coronary arteries
      (fibromuscular hyperplasia). The changes, which were widespread in both
      ventricles, resembled those of HCM in man and other animals.

PMID- 9263848
TI  - Heterotopic neural tissue in the pharynx of a 7-week-old kitten.
AB  - A 7-week-old male kitten had a pharyngeal mass (1 x 2 cm) causing displacement of
      the tongue. The surgically resected tissue was seen to be a moderately discrete
      subepithelial mass comprising islands of neuroglia and neurons separated by dense
      collagenous connective tissue. It is not known whether this mass retained any
      connection with the brain. Histochemical and immunohistochemical examination
      confirmed the presence of neurons and a pleocellular glial population, supporting
      a diagnosis of heterotopic neural tissue. The cat remained well 20 months after
      surgical treatment. Heterotopic neural tissue is well-recognized in man but has
      not been described in animals.

PMID- 9263849
TI  - A comparison of heuristic search algorithms for molecular docking.
AB  - This paper describes the implementation and comparison of four heuristic search
      algorithms (genetic algorithm, evolutionary programming, simulated annealing and
      tabu search) and a random search procedure for flexible molecular docking. To our
      knowledge, this is the first application of the tabu search algorithm in this
      area. The algorithms are compared using a recently described fast molecular
      recognition potential function and a diverse set of five protein-ligand systems.
      Statistical analysis of the results indicates that overall the genetic algorithm
      performs best in terms of the median energy of the solutions located. However,
      tabu search shows a better performance in terms of locating solutions close to
      the crystallographic ligand conformation. These results suggest that a hybrid
      search algorithm may give superior results to any of the algorithms alone.

PMID- 9263850
TI  - An automated method for predicting the positions of hydrogen-bonding atoms in
      binding sites.
AB  - Hydrogen bonds are the most specific, and therefore predictable of the
      intermolecular interactions involved in ligand-protein binding. Given the
      structure of a molecule, it is possible to estimate the positions at which
      complementary hydrogen-bonding atoms could be found. Crystal-survey data are used
      in the design of a program, HBMAP, that generates a hydrogen-bond map for any
      given ligand, which contains all the feasible positions at which a complementary
      atom could be found. On superposition of ligands, the overlapping regions of
      their maps represent positions of receptor atoms to which each molecule can bind.
      The certainty of these positions is increased by the incorporation of a larger
      number and diversity of molecules. In this work, superposition is achieved using
      the program HBMATCH, which uses simulated annealing to generate the
      correspondence between points from the hydrogen-bonding maps of the two
      molecules. Equivalent matches are distinguished on the basis of their steric
      similarity. The strategy is tested on a number of ligands for which ligand
      protein complexes have been solved crystallographically, which allows validation
      of the techniques. The receptor atom positions of thermolysin are successfully
      predicted when the correct superposition is obtained.

PMID- 9263851
TI  - A Monte Carlo method for finding important ligand fragments from receptor data.
AB  - A simulated annealing method for finding important ligand fragments is described.
      At a given temperature, ligand fragments are randomly selected and randomly
      placed within the given receptor cavity, often replacing or forming bonds with
      existing ligand fragments. For each new ligand fragment combination, the bonded,
      nonbonded, polarization and solvation energies of the new ligand-receptor system
      are compared to the previous configuration. Acceptance or rejection of the new
      system is decided using the Boltzmann distribution e-E/kT, where E is the energy
      difference between the old and new systems, k is the Boltzmann constant and T is
      the temperature. Thus, energetically unfavorable fragment switches are sometimes
      accepted, sacrificing immediate energy gains in the interest of findings a system
      with minimum energy. By lowering the temperature, the rate of unfavorable
      switches decreases and energetically favorable combinations become more difficult
      to change. The process is terminated when the frequency of switches becomes too
      small. As a test, the method predicted positions and types of important ligand
      fragments for neuraminidase that were in accord with the known ligand, sialic
      acid.

PMID- 9263852
TI  - Molecular modelling studies of substrate binding to the lipase from Rhizomucor
      miehei.
AB  - Lipase enzymes have found increasingly widespread use, especially in
      biotransformation reactions in organic synthesis. Due to their efficiency and
      high enantioselectivity, they can be employed in a variety of reactions to carry
      out asymmetric hydrolyses, esterifications and transesterifications. However, the
      reasons for their stereospecificity have not been fully correlated with the
      enzyme structure. Employing molecular modelling techniques and existing
      experimental data, a transesterification reaction using Rhizomucor miehei lipase
      was studied. The results indicate that the major controlling factor for this
      reaction is hydrophobic in nature, providing support for previous literature
      hypotheses. In addition, computational experiments suggest that the origin of
      enantioselectivity is the formation of essential hydrogen bonds in and around the
      catalytic triad of active site residues. Only one enantiomer of the substrate is
      able to form these hydrogen bonds during the formation of the first tetrahedral
      transition state.

PMID- 9263853
TI  - Molecular modeling of cytochrome P450 3A4.
AB  - The three-dimensional structure of human cytochrome P450 3A4 was modeled based on
      crystallographic coordinates of four bacterial P450s; P450 BM-3, P450cam,
      P450terp, and P450eryF. The P450 3A4 sequence was aligned to those of the known
      proteins using a structure-based alignment of P450 BM-3, P450cam, P450terp, and
      P450eryF. The coordinates of the model were then calculated using a consensus
      strategy, and the final structure was optimized in the presence of water. The
      P450 3A4 model resembles P450 BM-3 the most, but the B' helix is similar to that
      of P450eryF, which leads to an enlarged active site when compared with P450 BM-3,
      P450cam, and P450terp. The 3A4 residues equivalent to known substrate contact
      residues of the bacterial proteins and key residues of rat P450 2B1 are located
      in the active site or the substrate access channel. Docking of progesterone into
      the P450 3A4 model demonstrated that the substrate bound in a 6 beta-orientation
      can interact with a number of active site residues, such as 114, 119, 301, 304,
      305, 309, 370, 373, and 479, through hydrophobic interactions. The active site of
      the enzyme can also accommodate erythromycin, which, in addition to the residues
      listed for progesterone, also contacts residues 101, 104, 105, 214, 215, 217,
      218, 374, and 478. The majority of 3A4 residues which interact with progesterone
      and/or erythromycin possess their equivalents in key residues of P450 2B enzymes,
      except for residues 297, 480 and 482, which do not contact either substrate in
      P450 3A4. The results from docking of progesterone and erythromycin into the
      enzyme model make it possible to pinpoint residues which may be important for 3A4
      function and to target them for site-directed mutagenesis.

PMID- 9263854
TI  - Is the parallel or antiparallel beta-sheet more stable? A semiempirical study.
AB  - The geometry and energy of parallel and antiparallel peptidic beta-sheets have
      been calculated using AM1. beta-Sheets composed of two peptide chains of up to 11
      amino acid residues (Ala and Gly) and the dimers of cyclooctapeptides are used as
      model systems. The enthalpic difference between the parallel and the antiparallel
      arrangement is calculated to be very small, as it is found experimentally for the
      cyclic systems. The coordinates of the calculated structure of the
      cyclooctapeptide dimer 1 (cyclo-D,L-(Ala)8) have an rms deviation of only 0.223 A
      to the coordinates of the corresponding cyclopeptide obtained by X-ray analysis.

PMID- 9263855
TI  - Structure-activity relationships of cannabinoids: a joint CoMFA and
      pseudoreceptor modelling study.
AB  - A cannabinoid pseudoreceptor model for the CB1-receptor has been constructed for
      31 cannabinoids using the molecular modelling software YAK. Additionally, two
      CoMFA studies were performed on these ligands, the first of which was conducted
      prior to the building of the pseudoreceptor. Its pharmacophore is identical with
      the initial superposition of ligands used for pseudoreceptor construction. In
      contrast, the ligand alignment for the second CoMFA study was taken directly from
      the final cannabinoid pseudoreceptor model. This altered alignment gives markedly
      improved cross-validated r2 values as compared to those obtained from the
      original alignment with r2 cross values of 0.79 and 0.63, respectively, for five
      components. However, the pharmacophore alignment has the better predictive
      ability. Both the CoMFA and pseudoreceptor methods predict the free energy of
      binding of test ligands well.

PMID- 9263857
TI  - CAMDAS: an automated conformational analysis system using molecular dynamics.
      Conformational Analyzer with Molecular Dynamics And Sampling.
AB  - We present an automated conformational analysis program, CAMDAS (Conformational
      Analyzer with Molecular Dynamics And Sampling). CAMDAS performs molecular
      dynamics (MD) calculations for a target molecule and samples conformers from the
      trajectory of the MD. The program then evaluates the similarities between each of
      the sampled conformers in terms of the root-mean-square deviations of the atomic
      positions, clusters similar conformers, and finally prints out the clustered
      conformers. This MD-based conformational analysis is a broadly used method, and
      CAMDAS is intended to provide a convenient framework for the method. CAMDAS has
      the ability to find the representative conformers automatically from an
      arbitrarily given structure of the molecule. The accuracy of the program was
      examined using N-acetylalanine-N'-methylamide, and the obtained result was
      consistent with that of the systematic search method. In the test calculation of
      cyclodecane, CAMDAS could identify most of the known conformers and their
      conformational enantiomers by examining only 5000 conformers. In addition, the
      potential-scaled method, which we have developed previously as an accelerating
      technique for MD, could find two additional conformers of cyclodecane that have
      not been reported. CAMDAS presents a convenient way to find the energetically
      possible conformers of a molecule, which is needed especially in the early stage
      of drug design.

PMID- 9263858
TI  - Pulmonary autografts: the unresolved issues.

PMID- 9263859
TI  - The International Registry of the Ross procedure: 1996 results.

PMID- 9263860
TI  - The Ross procedure in children and young adults with congenital aortic valve
      disease.
AB  - METHODS: Thirty-three children and young adults with congenital aortic valve
      disease underwent pulmonary autograft replacement of the aortic valve between
      October 1993 and March 1997. There wer six females and 27 males; at operation,
      median age was 16 years (range: 3 to 41 years) and median body weight 60 kg
      (range: 14 to 121 kg). Fifteen patients (46%) had undergone one or more previous
      cardiac surgical procedures. A bicuspid aortic valve was present in 31 patients
      (94%); moderate to severe aortic stenosis and regurgitation was present in 10
      (30%) and 26 (79%), respectively. RESULTS: All patients underwent the Ross
      procedure while in NYHA class I (64%) or class II (36%). A preoperative
      shortening fraction of 41 +/- 1.4% suggested well-preserved systolic function,
      but the mean left ventricular end-diastolic pressure of 16.6 +/- 1.3 mmHg was
      consistent with preoperative left ventricular pressure and volume overload. The
      aortic root was replaced using an interrupted suture technique in two patients
      and with three separate running sutures in 31. The right ventricular outflow
      tract was reconstructed in all classes with a cryopreserved pulmonary homograft
      valved conduit (median diameter 23 mm; range 19 to 30 mm). Intraoperative
      complications included transient atrioventricular dissociation (one), permanent
      atrioventricular dissociation (one), and left coronary artery distortion relieved
      by shortening the distal ascending aorta (one). Postoperatively,
      postpericardiotomy syndrome developed in six patients (18%), supraventricular
      tachycardia in three (9%), and ventricular tachycardia in one (3%). At three days
      after surgery, one patient developed ischemic left ventricular dysfunction
      requiring repositioning of the distorted left coronary artery higher on the neo
      aortic root. Hospital survival rate was 100%. During a median follow-up of 17
      months (range: 1 to 41 months) one patient suffered a non-cardiac death due to
      blunt trauma. there has been a significant postoperative improvement in NYHA
      class among surviving patients (class I, 94%; class II, 6%; p = 0.004 versus
      preoperative). Postoperative aortic regurgitation was absent or trivial in 17
      (60%) and mild in the remaining 11 (40%) patients for whom follow-up
      echocardiographic data are available. One patient required reoperation 16.5
      months after the Ross procedure to replace a rapidly degenerating pulmonary
      homograft, and one with moderately severe homograft stenosis and five with mild
      homograft stenosis are being monitored. Postoperatively, a gradual early
      expansion in the diameter of the neo-aortic root and reduction in
      echocardiographic indices of left ventricular hypertrophy and dilatation
      occurred. CONCLUSIONS: Pulmonary autograft replacement of the aortic valve in
      young patients with congenital aortic valve disease has produced excellent short
      term anatomic/physiologic results and symptomatic relief with no mortality.
      Indices of left ventricular dilatation and hypertrophy regress after repair when
      the Ross operation precedes important deterioration in preoperative ventricular
      function. Important technical considerations include: (i) the native distal
      ascending aorta should be sufficiently shortened before performing the distal
      aortic anastomosis; and (ii) the left coronary anastomosis should be positioned
      relatively high on the neo-aortic root with a slight amount of tension. Both of
      these maneuvers reduce the likelihood of coronary artery distortion. Rapid
      degeneration of the pulmonary homograft and the propensity towards progressive
      dilatation of the neo-aorta are important postoperative considerations. Until
      more is known about the etiology and natural history of these two potential
      complications, postoperative anti-inflammatory and/or immunosuppressive therapy
      and strict control of hypertension should be strongly considered.

PMID- 9263861
TI  - Current techniques to reduce blood loss after the Ross procedure.
AB  - BACKGROUND AND AIMS OF THE STUDY: Although pulmonary autograft (PA) offers many
      theoretical advantages, the operation is more complex and the need for extensive
      reconstruction carries an increased risk for postoperative bleeding. The study
      aim was to evaluate the impact of different pharmacological and surgical
      strategies on total blood loss and blood product requirements after PA use.
      METHODS: Between July 1994 and March 1997, 26 patients (22 males) with a mean age
      of 26 +/- 8 years (range: 11 to 36 years) underwent aortic valve replacement with
      PA (22 root; four subcoronary implant). A relatively high incidence of re
      exploration for bleeding (n = 3) and significant total blood loss during our
      early experience (Group I, n = 8), prompted the subsequent introduction of
      different strategies (Group II, n = 18). These included perioperative use of
      aprotinin, reinforcement of suture lines of the neo-aortic root with autologous
      pericardium and accurate hemostasis of the raw surface on the back of the right
      ventricular outflow tract (RVOT) during a brief period of circulatory arrest,
      also with application of fibrin glue, RESULTS: There were no hospital deaths. No
      patients in group II required re-exploration or transfusion, and mean total
      postoperative blood loss was reduced (group I, 720 +/- 465 ml/m2 body surface
      area (BSA), versus group II, 323 +/- 84 ml/m2 BSA). By-pass and aortic cross
      clamp times were not significantly longer in group II patients. At a mean follow
      up of 15 months, all 25 survivors are asymptomatic, in NYHA functional class I,
      and with normal social interactions. CONCLUSIONS: Early survival after aortic
      valve replacement with the PA appears comparable with the use of more
      conventional valve substitutes. Blood loss containment by routine application of
      medical and surgical strategies appears feasible. In view of the common concern
      about blood transfusion, particularly in young patients, these findings may help
      to widen the range of indications for the Ross procedure.

PMID- 9263856
TI  - A theoretical model for the Gla-TSR-EGF-1 region of the anticoagulant cofactor
      protein S: from biostructural pathology to species-specific cofactor activity.
AB  - Protein S (PS), which functions as a species-specific anticoagulant cofactor to
      activated protein C (APC), is a mosaic protein that interacts with the
      phospholipid membrane via its gamma-carboxyglutamate-rich (Gla) module. This
      module is followed by the thrombin-sensitive region (TSR), sensitive to thrombin
      cleavage, four epidermal growth factor (EGF)-like modules and a last region
      referred to as the sex hormone binding globulin (SHBG) domain. Of these, the TSR
      and the first EGF-like regions have been shown to be important for the species
      specific interaction with APC. Difficulties in crystallising PS have so far
      hindered its study at the atomic level. Here, we report theoretical models for
      the Gla and EGF-1 modules of human PS constructed using prothrombin and factor X
      experimental structures. The TSR was built interactively. Analysis of the model
      linked with the large body of biochemical literature on PS and related proteins
      leads to suggestions that (i) the TSR stabilises the calcium-loaded Gla module
      through hydrophobic and ionic interactions and its conformation depends on the
      presence of the Gla module; (ii) the TSR does not form a calcium binding site but
      is protected from thrombin cleavage in the calcium-loaded form owing to short
      secondary structure elements and close contact with the Gla module; (iii) the PS
      missense mutations in this region are consistent with the structural data, except
      in one case which needs further investigation; and (iv) the two PS 'faces'
      involving regions of residues Arg49-Gln52-Lys97 (TSR-EGF-1) and Thr103-Pro106
      (EGF-1) may be involved in species-specific interactions with APC as they are
      richer in nonconservative substitution when comparing human and bovine protein S.
      This preliminary model helps to plan future experiments and the resulting data
      will be used to further validate and optimise the present structure.

PMID- 9263862
TI  - Factors influencing medium-term performance of right-sided cryopreserved
      homografts.
AB  - BACKGROUND OF THE STUDY: Between February 1987 and December 1996, 187 children
      and young adults underwent right ventricular outflow tract (RVOT) reconstruction
      with aortic or pulmonary homografts. METHODS: Patients were allocated to four
      groups according to preoperative diagnosis: RVOT obstructions with ventriculo
      arterial (VA) concordance (n = 90), RVOT obstructions with VA discordance (n =
      26), truncus arteriosus (n = 19) and RVOT reconstruction after the Ross procedure
      (n = 52). RVOT reconstruction was a reoperation in 49.7% of cases. A pulmonary
      homograft was used in preference (87% in concordant, 90% in Ross, 79% in truncus,
      and 50% in discordant groups). RESULTS: Five patients died after homograft repair
      (hospital mortality rate 2.7%). Mean follow up was 34 +/- 27 months. Four
      patients died during subsequent follow up; hence actuarial survival rate was 93
      +/- 2% at 60 months. All other patients are currently in NYHA class I or II. Nine
      patients underwent reoperation because of homograft dysfunction. Overall survival
      was 90 +/- 3% at 60 months. CONCLUSIONS: Uni- and multivariate analysis
      identified young age at correction, the use of aortic homografts, corrections in
      patients with VA discordance, and longer aortic cross-clamp time as independent
      predictors of homograft failure.

PMID- 9263863
TI  - The influence of geometric mismatch between the native aortic, native pulmonary
      and homograft pulmonary valve on the results of the pulmonary autograft
      operation.
AB  - BACKGROUND: The pulmonary autograft operation has achieved broad acceptance and
      may be the ideal aortic valve substitute. Both the pulmonary autograft and the
      aortic homograft are more complicated procedures than prosthetic valve
      replacement. The trend to insert the pulmonary autograft as a root replacement
      rather than in the subcoronary position has achieved greater uniformity in the
      results, but there is still confusing diversity in opinions on technical details
      and anatomical dimensions. The importance of both size and shape mismatches
      between the three valves involved has received little attention. The valves often
      differ in diameter and in the shape of the recipient aortic annulus. This
      uncertainty and the diversity of opinions on essential technical details was
      disconcerting when we proceeded from aortic homograft-to-pulmonary autograft
      operations, this was compounded by only a single homograft being available for
      every operation as we have no homograft bank. METHODS: We compared the
      hemodynamic results regarding various geometric mismatches. All operative details
      were the same and patients were studied at regular intervals. Comparisons were
      made in patients with mismatch between recipient aortic annulus and pulmonary
      autograft. Patients with a normal tricuspid aortic annulus were compared to those
      with either a circular redo prosthetic valve annulus or a bicuspid recipient
      annulus. Thirdly we compared the patients with plication of the aortic annulus to
      those with remodeling of the distal aorta. Lastly we compared mismatch between
      donor homograft and pulmonary autograft. RESULTS: No influence of geometric
      mismatch between the three valves could be found on the results of the pulmonary
      autograft operation. CONCLUSIONS: Good results are obtainable without a painful
      learning curve if one keeps to certain surgical principles. It need not be a
      complicated operation and geometric mismatches between the three valves involved
      may be compensated for adequately.

PMID- 9263864
TI  - Coronary translocation during aortic root replacement with the pulmonary
      autograft: complications and their management.
AB  - BACKGROUND AND AIMS OF THE STUDY: Aortic root replacement with the pulmonary
      autograft has become an alternative to replacement of the diseased aortic valve
      with mechanical or biological prostheses. Due to greater technical complexity of
      the operation, complications with autograft root replacement (ARR) may be more
      common. In particular, a higher prevalence of coronary complications has been
      suggested. METHODS: In order to assess the prevalence, cause and management of
      coronary complications after ARR, results with 26 consecutive operations were
      reviewed and compared with previously published series. Between July 1994 and
      Apri 1997, 22 males and four females (mean age 26 +/- 8 years; range: 11 to 36
      years) underwent aortic root (n = 22) or valve replacement (n = 4) with a
      pulmonary autograft for regurgitation (n = 14), stenosis (n = 4) or both (n = 8).
      Associated lesions were present in 10 (38%) patients, including three cases of
      major coronary artery anomalies such as origin of the circumflex from the right
      coronary sinus, high origin of the right coronary, aneurysmal and calcified right
      and left main coronaries, both in one patient. RESULTS: There were no early
      deaths. Major complications occurred in six patients; re-exploration for bleeding
      was required in three (11%) and partial take down of repair for coronary
      complications in three (11%), all with preoperative coronary anomalies. Two of
      the latter patients presented with intraoperative right ventricular ischemia due
      to kinking of the right coronary (corrected by re-implantation at a higher
      level), and one had intraoperative hemorrhage due to rupture of a calcified left
      main coronary, which required transection of the pulmonary homograft above the
      valve to expose the tear. Recovery was prompt in all patients (mean ICU stay 35
      +/- 28 h) with no metabolic or electrocardiographic evidence of ischemia.
      Echocardiography at discharge showed satisfactory biventricular kinetics in all;
      mild regurgitation of the autograft was found in two (8%) who had undergone
      subcoronary implant, and absent or trivial in 22 (92%). One patient died suddenly
      13 months after ARR; hence actuarial survival rate was 100% and 96% at 12 and 24
      months, respectively. At mean follow up of 15 +/- 11 months (range 1 to 32
      months), all patients are in NYHA class I and have returned to school or prior
      employment. CONCLUSIONS: Complications with coronary artery translocation during
      ARR may be a definite risk, particularly in the presence of coronary anomalies.
      Prompt recognition and an aggressive intraoperative approach, including partial
      take down of the repair, may limit the morbidity of this complex surgical
      procedure.

PMID- 9263865
TI  - Valve repair in rheumatic mitral valve disease: is it always worth trying?

PMID- 9263866
TI  - The appropriateness of mitral valve repair for rheumatic mitral valve disease.

PMID- 9263867
TI  - The wisdom of repairing stenotic mitral lesions.

PMID- 9263868
TI  - Repair versus replacement for mitral stenosis.

PMID- 9263869
TI  - Hemodynamic assessment of replacement valves in the aortic position: is stress
      echocardiography necessary?

PMID- 9263871
TI  - Perioperative morbidity and mortality in combined aortic and mitral valve
      surgery.
AB  - BACKGROUND AND AIMS OF THE STUDY: Despite many significant improvements in
      cardiac surgical technique, the operative risk for combined aortic and mitral
      valve surgery remains between 5% and 12%. Identification of high-risk patients
      will allow surgeons to develop strategies to improve these results. METHODS: The
      30-day postoperative mortality and complication rates were analyzed in a group of
      206 patients operated on over a 16-year period with cold crystalloid
      cardioplegia. Thirty-three possible risk factors for death and low output
      syndrome (LOS) were entered into univariate and multivariate logistic regression
      analysis. RESULTS: There were 10 perioperative deaths (4.9%). Major complications
      occurred in 38 patients (18.4%), 19 with LOS. On univariate analysis, right
      atrial pressure (RAP) > or = 8 mmHg (p = 0.001), aortic stenosis (p = 0.009) and
      systolic pulmonary artery pressure > or = 60 mmHg (p = 0.095) were found to be
      risk factors for death, as were RAP > or = 8 mmHg (p = 0.001), previous heart
      surgery (p = 0.007), serum creatinine > or = 120 mumol/l (p = 0.03), tricuspid
      valve disease (p = 0.038) and aortic stenosis (p = 0.09) for LOS. On multivariate
      analysis, RAP > or = 8 mmHg (p < 0.001) and aortic stenosis (p = 0.002) were
      identified as independent risk factors for death, as were RAP > or = 8 mmHg (p =
      0.001) and previous heart surgery (p = 0.008) for LOS. CONCLUSIONS: Mitro-aortic
      valve surgery involves complex procedures with substantial mortality and
      morbidity. The risk factors point toward the importance of operating before the
      stage of advanced heart failure and toward the key role of better myocardial
      protection techniques in these compromised hearts with limited reserves.

PMID- 9263870
TI  - Invasive evaluation of mitral regurgitation: the importance of hemodynamic
      measurements during exercise.
AB  - BACKGROUND AND AIMS OF THE STUDY: In patients with mitral regurgitation, left
      ventricular angiography is usually performed to grade the regurgitation. This is
      a semi-quantitative method which gives some information related to the
      regurgitant volume at a certain time. The aim of our study was to evaluate the
      benefits of invasive hemodynamic examinations during stress. Patients with mitral
      regurgitation according to Doppler color flow mapping, and regurgitation of no
      more than grade 2+ according to left ventricular angiography, were of special
      interest. METHODS: One hundred and four consecutive patients were examined with
      transesophageal echocardiography (TEE), left ventricular angiography and cardiac
      catheterization during rest and during hemodynamic stress. RESULTS: All patients
      had mitral regurgitation according to Doppler color flow mapping. Thirty eight
      patients had a mitral regurgitation of grade 0, 1+ or 2+ according to left
      ventricular angiography. Of these, seven had a resting v-wave < or = 25 mmHg, and
      a v wave > or = 50 mmHg during stress. When these seven patients were compared
      with those with severe grade 3+ and 4+ regurgitation, there was a significant
      difference between the v-wave at rest (p = 0.02) but no significant difference
      during stress (p = 0.42). CONCLUSIONS: Mitral regurgitation is a dynamic lesion,
      the complete assessment of which cannot be obtained from a single measure during
      one hemodynamic situation. Additional information from v-wave recordings during
      hemodynamic stress identified a subgroup of patients who had near-normal
      pressures at rest, but whose v-wave measurements during stress did not differ
      significantly from those of patients with severe angiographically assessed
      regurgitation (grades 3+ and 4+). In patients with only minor mitral
      regurgitation which is suspected to contribute to their clinical symptoms, the
      monitoring of invasive hemodynamic parameters during stress is important.

PMID- 9263872
TI  - Improved regional left ventricular performance in mitral valve replacement with
      orthotopic refixation of the anterior mitral leaflet.
AB  - BACKGROUND AND AIMS OF THE STUDY: To investigate the influence of different
      surgical techniques of chordal preservation in mitral valve replacement (MVR) on
      left ventricular size and function, we studied a series of 244 patients who
      underwent mitral valve replacement either with (n = 161) or without (n = 83)
      preservation of the subvalvular structures. RESULTS: Preoperatively there were no
      differences between the two patient groups. Three months postoperatively,
      echocardiography demonstrated that chordal preservation in MVR resulted in
      smaller left ventricular end-systolic diameter (LVESD) and end-diastolic diameter
      (LVEDD): preservation versus resection, LVESD: 43.4 +/- 7.8 mm versus 48.8 +/-
      9.2 mm (p < 0.05), LVEDD: 57.3 +/- 7.8 mm versus 62.9 +/- 10.5 mm (p < 0.05) and
      a significantly decreased LV-L (long axis) (87.1 +/- 4.2 mm versus 97.5 +/- 5.7
      mm; p < 0.05). There was no significant difference in cardiac dimensions between
      the three patient subgroups in whom chordal preservation was possible. In
      addition, left ventricular ejection fraction in the preservation groups was
      significantly improved compared with the resection group (54.2 +/- 11.2% versus
      48.1 +/- 12.4%, p < 0.05); there were no differences between the preservation
      subgroups. Regional wall motion analysis revealed significantly improved
      segmental myocardial performance in all segments if both leaflets were preserved
      or the anterior mitral leaflet was reattached to the anterior mitral annulus.

PMID- 9263873
TI  - Choice of replacement valve in the elderly.
AB  - BACKGROUND AND AIMS OF THE STUDY: Little comparative information exists on the
      outcome of the valve replacement with bioprostheses or mechanical valves in the
      elderly. This study was carried out to make such a comparison. METHODS: Follow up
      data were examined from 219 patients aged > or = 65 years who underwent aortic
      and/or mitral valve replacement using bioprosthetic (n = 67) or mechanical valve
      (n = 152) between April 1979 and December 1993. The mean follow up periods were
      6.3 +/- 2.8 years after bioprosthesis and 4.9 +/- 2.1 years after mechanical
      valve implantation. RESULTS: Although the actuarial rate of structural
      deterioration was higher in patients with bioprosthetic valves than in those with
      mechanical valves (58% versus 100% freedom at 10 years after surgery, p < 0.01),
      no such prosthesis-related difference was seen in the subgroup of patients aged >
      or = 70 (100% versus 100% at nine years, p = N.S.). The actuarial rate of major
      bleeding was higher after mechanical valve implantation than after bioprosthetic
      valve placement (90% versus 100% freedom at 10 years, p < 0.05); this lower rate
      with bioprosthetic valves was maintained in patients aged > or = 70 (78% versus
      100% at nine years, p < 0.05). There were no significant differences in the
      incidences of thromboembolism and bacterial endocarditis between the two valve
      types. CONCLUSIONS: Structural degeneration of bioprosthetic devices was a major
      problem in patients aged 65-70 years, but it was essentially negligible in those
      aged > or = 70 years. Anticoagulant-related bleeding was a major problem with
      mechanical valves in both age groups. Therefore, for patients older than 70
      years, valve replacement with a bioprosthesis appears to be the method of choice.

PMID- 9263874
TI  - The Bicarbon heart valve prosthesis: short-term results.
AB  - BACKGROUND AND AIMS OF THE STUDY: To determine the short-term results of the
      Bicarbon (Sorin Biomedica, Saluggia, Italy) heart valve prosthesis at our
      institution. METHODS: Between November 1991 and December 1995, 256 patients (mean
      age 59.9 +/- 9.8 years) underwent valve replacement with a Bicarbon valve
      prosthesis. The mean ejection fraction was 60 +/- 14.8% and the mean left
      ventricular end-diastolic pressure 15.9 +/- 8.7 mmHg. Redo (n = 61) and combined
      procedures (n = 72) were included in this study; mixed types of prostheses were
      excluded. The procedures were divided into groups: aortic valve replacement (n =
      163), mitral valve replacement (n = 60) and aortic-mitral (double) valve
      replacement (n = 33). Kaplan-Meier survival analysis was performed and predictors
      for survival were tested univariately and multivariately. RESULTS: The mean
      follow up was 30 +/- 25.1 months with a total of 7,696 patient-months (641.3
      patient-years) and was 100% complete. The Kaplan-Meier survival rate at 48 months
      was 87 +/- 2%. The valve-related morbidity expressed as linearized incidence rate
      (% per patient-year) was: anticoagulation bleeding 2.3 +/- 0.6; thromboembolic
      event 1.0 +/- 0.4; periprosthetic leak 0.6 +/- 0.3; and endocarditis 0.3 +/- 0.2.
      Univariate significant factors for worse survival were: higher preoperative New
      York Heart Association (NYHA) functional class, valve implantation site, presence
      of associated operation, increasing age, decreasing ejection fraction, longer
      aortic cross-clamp time, and longer cardiopulmonary bypass time. In multivariate
      analysis longer aortic cross-clamp time and higher preoperative NYHA
      classification were significant independent predictors. CONCLUSIONS: These good
      short-term results after Bicarbon valve replacement are encouraging and
      comparable with those obtained with other bileaflet mechanical heart valves.
      However, further follow up is mandatory.

PMID- 9263875
TI  - Chemical modification of bovine tissues by dye-mediated photooxidation.
AB  - BACKGROUND AND AIMS OF THE STUDY: Photooxidation of pericardium has been shown
      chemically to alter and stabilize tissue. The characterization of
      photooxidatively induced, chemical modifications of bovine pericardial and
      arterial tissue is reported here. METHODS: Tissues were prepared by various
      methods of photooxidation and analyzed for thermal denaturation temperature,
      protein extraction, amino acid content and crosslink content. RESULTS:
      Photooxidation of tissue resulted in no significant time-dependent changes in
      thermal denaturation temperature, but did result in a time-dependent alteration
      and reduction in extracted proteins. This reduction is consistent with chemical
      alteration and stabilization of the tissue. Photooxidation also resulted in a
      time-dependent reduction of histidine content in treated tissues by histidine
      being converted to a non-detectable form. No other amino acid alteration was
      detected by amino acid analysis. Crosslink analysis of tissue hydrolyzates showed
      a time-dependent alteration in crosslink content of photooxidized tissue and an
      apparent addition of several types of new crosslinks. CONCLUSIONS: These chemical
      modifications are consistent with oxidative modification of amino acids in the
      tissues, resulting in an alteration of existing crosslinks and possible addition
      of new crosslinks in the tissues. This treatment process leads to in vivo and in
      vitro stability of pericardial and arterial tissues with potential use as
      bioprosthetic materials.

PMID- 9263877
TI  - The influence of sizing and method of fixation on the hydrodynamic function of
      stentless, free-hand inserted porcine bioprosthesis: an in vitro study.
AB  - BACKGROUND AND AIMS OF THE STUDY: There is increasing interest in the use of
      stentless porcine bioprostheses implanted by the free-hand suturing technique.
      However, preservation of normal valve geometry and function is a matter of
      concern. This in vitro study was conducted to investigate the influence of sizing
      and method of fixation in glutaraldehyde on the hydrodynamic function of
      stentless, free-hand inserted porcine bioprosthetic valves in the aortic
      position. METHODS: Three sets of porcine aortic roots were used, with six
      specimens in each set. Group A comprised 2-3 mm larger aortic valve (oversizing)
      fixed in glutaraldehyde under zero pressure inserted by free-hand suturing
      technique in fresh aortic roots; group B comprised size-for-size placement of
      aortic valve fixed in glutaraldehyde under zero pressure inserted by free-hand
      suturing technique in fresh aortic roots; and group C comprised size-for-size
      placement of aortic valve fixed in glutaraldehyde under zero pressure with
      permanent predilatation before fixation inserted by free-hand suturing technique
      in fresh aortic roots (undersizing). Hydrodynamic function and leaflet bending
      deformations were analyzed in a modified pulsatile flow simulator which
      incorporated the elastic aortic roots. RESULTS: The hydraulic effective orifice
      area (EOA) of the valve (derived from flow and pressure measurements) was divided
      by actual orifice area of the annulus to determine the performance index.
      Although statistically non-significant, the performance index of 0.50 in group A
      (oversizing) was higher than that of size-for-size placement in group B (0.39).
      The performance index in group C of 0.41, following use of a permanent
      predilatation technique, was again not significantly different. The mean pressure
      difference during peak flow followed a correspondingly reversed order, with 11.4
      mmHg in group B, 8.86 mmHg in group C, and 7.75 mmHg in group A. No significant
      difference was observed between the groups in terms of open leaflet bending
      deformations, nor was there any inter-group difference in regurgitation.
      CONCLUSIONS: No beneficial effect was seen to suggest that size-for-size
      placement was superior to the currently followed practice of over-sizing. In
      contrast to previous studies of whole root replacement, permanent predilatation
      and fixation was also not shown to have any additional advantages in a stentless
      scalloped free-hand inserted porcine valve.

PMID- 9263876
TI  - High-resolution magnetic resonance imaging to characterize the geometry of
      fatigued porcine bioprosthetic heart valves.
AB  - BACKGROUND AND AIMS OF THE STUDY: Porcine bioprosthetic heart valves (PBHV)
      continue to suffer from limited long-term durability. Failure of PBHV occurs
      mainly in the cusps and is characterized by mechanical damage, usually in
      conjunction with calcification. Mechanisms underlying calcification have received
      considerable attention, yet mechanical damage phenomena remain poorly understood.
      The structural response of PBHV cusps to in-vivo cyclic loading involves three
      primary factors: (i) mechanical properties; (ii) fiber architecture; and (iii) 3D
      geometry. Previous finite element studies have shown cuspal stress distribution
      to be highly sensitive to subtle changes in geometry, yet to date, cusp geometry
      has been largely ignored in studies of PBHV durability. METHODS: A non
      destructive method was developed to quantify PBHV 3D geometry using high
      resolution magnetic resonance (MR) imaging. Images were obtained in three
      orthogonal planes from virgin and accelerated tested (50 x 10(6) and 200 x 10(6)
      cycles) PBHVs to fully capture 3D cuspal geometry. Surface curvatures were
      computed using a local biquadric surface patch approach. RESULTS: Results
      indicated a tendency for cusps to permanently deform with accelerated testing,
      manifesting primarily as sagging of the cusp. This sagging induced areas of high
      curvature from the central belly region upwards to the nodulus of Aranti,
      corresponding to known locations of tissue failure. CONCLUSIONS: It is likely
      that the observed changes in cuspal geometry induce deleterious alterations in
      the stress distribution, independent of those related to mechanical properties
      and fiber structure, and contribute to valve failure. Our results suggest that
      PBHV designers should attempt to compensate for the deleterious geometric changes
      that occur post-implantation.

PMID- 9263878
TI  - An anomalous muscle bundle inside the right atrium possibly related to the right
      venous valve.
AB  - The right and left venous valves of the sinoatrial orifice regulate the flow of
      blood from the sinus venosus to the atrium in pisces, amphibians, and reptiles.
      In aves, mammals and humans, the venous valve loses its hemodynamic function and
      hence has become the 'Cinderella' among heart valves, receiving attention only
      when congenital anomalies occur that are related to it. The right venous valve
      persists in humans as the crista terminalis, Eustachian and Thebesian valves. An
      intraluminal muscle band is described located inside the right atrium, and
      coursing in the line of the crista terminalis between the septum spurium and
      inferior vena cava. This abnormal band is possibly derived from the right venous
      valve.

PMID- 9263879
TI  - Hemodynamic performance of the Edwards Prima stentless valve.

PMID- 9263881
TI  - A model of scorpion toxin binding to voltage-gated K+ channels.
AB  - Mutational studies have identified part of the S5-S6 loop of voltage-dependent K+
      channels (P region) responsible for tetraethylammonium (TEA) block and permeation
      properties. Several scorpion peptide toxins-charybdotoxin (ChTX), kaliotoxin
      (KITX), and agitoxin (AgTX)-also block the channel with high affinity and
      specificity. Here, we examine the interaction predicted when the toxins are
      docked onto the molecular model of the K+ channel pore that we recently proposed.
      Docking with the model of the Kv1.3 channel started by location of Lys-27 side
      chain into the central axis of the pore, followed by energy minimization. In the
      optimal arrangement, Arg-24 of KITX or AgTX forms a hydrogen bond with the Asp
      386 carboxyl of one subunit, and Asn-30 is in immediate contact with Asp-386 of
      the opposing subunit in the tetramer. Toxin residues in proximity to the side
      chain of Lys-27 (Phe-25, Thr-36, Met-29, and Ser-11 in KITX) interact with the
      four C-end His-404s. For ChTX the interaction with Asp-386 is reduced, but this
      is compensated by additional nonbonded interactions formed by Tyr-36 and Arg-34.
      Comparison of calculated energy of interaction of these specific toxin-channel
      residues with experimental studies reveals good agreement. The similar total
      calculated energy of interaction is consistent with the similar IC50 for Kv1.3
      block by KITX and AgTX. Steric contacts of residues in position 380 of the S5-P
      linker with residues on the upper part of toxins permit reconstruction of the K+
      channel outer vestibule walls, which are about 30 A apart and about 9 A high.
      Molecular modeling shows complementarity of the pore model to toxin spacial
      structures, and supports the proposal that the N-terminal borders of the P
      regions surround residues of their C-terminal halves.

PMID- 9263880
TI  - The molecular physiology of electroneutral cation-chloride cotransport.
AB  - The application of molecular biology to the study of electroneutral cation
      chloride cotransporters has been extremely successful, resulting in the
      identification of a new gene family of five membrane proteins. The function,
      expression, and regulation of these important proteins can increasingly be
      described in molecular terms. In addition, mutations in two renal cation-chloride
      transporter genes have been found in patients with Bartter's and Gitelman's
      syndromes, autosomal recessive disorders of renal salt excretion.

PMID- 9263882
TI  - Facilitation of membrane fusion during exocytosis and exocytosis-coupled
      endocytosis and acceleration of "ghost" detachment in Paramecium by extracellular
      calcium. A quenched-flow/freeze-fracture analysis.
AB  - We had previously shown that an influx of extracellular Ca2+ (Ca2+e), though it
      occurs, is not strictly required for aminoethyldextran (AED)-triggered exocytotic
      membrane fusion in Paramecium. We now analyze, by quenched-flow/freeze-fracture,
      to what extent Ca2+e contributes to exocytotic and exocytosis-coupled endocytotic
      membrane fusion, as well as to detachment of "ghosts"-a process difficult to
      analyze by any other method or in any other system. Maximal exocytotic membrane
      fusion (analyzed within 80 msec) occurs readily in the presence of [Ca2+]e > or =
      5 x 10(-6) M, while normally a [Ca2+]e = 0.5 mM is in the medium. A new finding
      is that exocytosis and endocytosis is significantly stimulated by increasing
      [Ca2+]e even beyond levels usually available to cells. Quenching of [Ca2+]e by
      EGTA application to levels of resting [Ca2+]i or slightly below does reduce (by
      approximately 50%) but not block AED-triggered exocytosis (again tested with 80
      msec AED application). This effect can be overridden either by increasing
      stimulation time or by readdition of an excess of Ca2+e. Our data are compatible
      with the assumption that normally exocytotic membrane fusion will include a step
      of rapid Ca(2+)-mobilization from subplasmalemmal pools ("alveolar sacs") and, as
      a superimposed step, a Ca(2+)-influx, since exocytotic membrane fusion can occur
      at [Ca2+]e even slightly below resting [Ca2+]i. The other important conclusion is
      that increasing [Ca2+]e facilitates exocytotic and endocytotic membrane fusion,
      i.e., membrane resealing. In addition, we show for the first time that increasing
      [Ca2+]e also drives detachment of "ghosts"-a novel aspect not analyzed so far in
      any other system. According to our pilot calculations, a flush of Ca2+, orders of
      magnitude larger than stationary values assumed to drive membrane dynamics, from
      internal and external sources, drives the different steps of the exo-endocytosis
      cycle.

PMID- 9263883
TI  - Mechanical properties of brush border membrane vesicles from kidney proximal
      tubule.
AB  - The mechanical properties of brush border membrane vesicles, BBMV, from rabbit
      kidney proximal tubule cells, were studied by measuring the initial and final
      equilibrium volumes of vesicles subjected to different osmotic shocks, using
      cellobiose as the impermeant solute in the preparation buffer. An elevated
      intracellular hydrostatic pressure was inferred from osmotic balance requirements
      in dilute solutions. For vesicles prepared in 18 and 85 mosM solutions, these
      pressures are close to 17 mosM (290 mm Hg). The corresponding membrane surface
      tension is 6.0 x 10(-5) N cm-1 while the membrane surface area is expanded by at
      least 2.2%. When these vesicles are exposed to very dilute solutions the internal
      hydrostatic pressure rises to an estimated 84 mosM (1444 mm Hg) just prior to
      lysis. The corresponding maximal surface tension (pre-lysis) is 18.7 x 10(-5) N
      cm-1, and the maximal expansion of membrane area is 6.8%. The calculated area
      compressibility elastic modulus was 2.8 x 10(-3) N cm-1.

PMID- 9263884
TI  - Water permeability of brush border membrane vesicles from kidney proximal tubule.
AB  - Brush border membrane vesicles (BBMV) maintain an initial hydrostatic pressure
      difference between the intra- and extravesicular medium, which causes membrane
      strain and surface area expansion (Soveral, Macey & Moura, 1997). This has not
      been taken into account in prior osmotic water permeability Pf evaluations. In
      this paper, we find further evidence for the pressure in the variation of stopped
      flow light scattering traces with different vesicle preparations. Response to
      osmotic shock is used to estimate water permeability in BBMV prepared with
      buffers of different osmolarities (18 and 85 mosM). Data analysis includes the
      dissipation of both osmotic and hydrostatic pressure gradients. Pf values were of
      the order of 4 x 10(-3) cm sec-1 independent of the osmolarity of the preparation
      buffer. Arrhenius plots of Pf vs. 1/T were linear, showing a single activation
      energy of 4.6 kcal mol-1. The initial osmotic response which is significantly
      retarded is correlated with the period of elevated hydrostatic pressure. We
      interpret this as an inhibition of Pf caused by membrane strain and suggest how
      this inhibition may play a role in cell volume regulation in the proximal tubule.

PMID- 9263885
TI  - 5-Lipoxygenase metabolites of arachidonic acid regulate volume decrease by
      mudpuppy red blood cells.
AB  - We examined whether metabolites of arachidonic acid (AA) regulate K+ efflux
      during regulatory volume decrease (RVD) by mudpuppy red blood cells (RBCs).
      Volume regulation was inhibited by the phospholipase A2 antagonists mepacrine (10
      microM) and ONO-RS-082 (10 microM); the inhibitory effect of ONO-RS-082 was
      reversed by gramicidin (5 microM). Eicosatetraynoic acid (ETYA, 100 microM), a
      general antagonist of AA metabolism, also blocked RVD. In addition, volume
      regulation was inhibited by the lipoxygenase pathway antagonist
      nordihydroguaiaretic acid (NDGA, 10 microM), the 5 lipoxygenase antagonists AA
      861 (5 microM) and curcumin (20 microM), and by the 5-lipoxygenase activating
      protein inhibitor L-655,298 (5 microM). Inhibition by all four of these agents
      was reversed with gramicidin. In contrast, the 12- and 15-lipoxygenase pathway
      inhibitor ethyl-3,4-dihydroxy-benzylidene-cyanoacetate (EDBCA, 1 microM) and the
      cytochrome P-450 monooxygenase pathway blocker ketoconazole (20 microM) had no
      effect. On the other hand, the cyclooxygenase pathway inhibitor aspirin (100
      microM) slightly enhanced RVD. Consistent with these findings, a K(+)-selective
      whole cell conductance responsible for K+ efflux during cell swelling was
      inhibited by ONO-RS-082 (10 microM), NDGA (10 microM), AA-861 (5 microM),
      curcumin (20 microM), and L-655,298 (5 microM). In contrast, EDBCA (1 microM),
      ketoconazole (20 microM), and indomethacin (10 microM) did not block this whole
      cell conductance. These results indicate that a channel mediating K+ loss during
      RVD is regulated by a 5-lipoxygenase metabolite of arachidonic acid.

PMID- 9263886
TI  - K(+)-sensitive gating of the K+ outward rectifier in Vicia guard cells.
AB  - The effect of extracellular cation concentration and membrane voltage on the
      current carried by outward-rectifying K+ channels was examined in stomatal guard
      cells of Vicia faba L. Intact guard cells were impaled with double-barrelled
      microelectrodes and the K+ current was monitored under voltage clamp in 0.1-30 mM
      K+ and in equivalent concentrations of Rb+, Cs+ and Na+. From a conditioning
      voltage of -200 mV, clamp steps to voltages between -150 and +50 mV in 0.1 mM K+
      activated current through outward-rectifying K+ channels (IK,out) at the plasma
      membrane in a voltage-dependent fashion. Increasing [K+]o shifted the voltage
      sensitivity of IK,out in parallel with the equilibrium potential for K+ across
      the membrane. A similar effect of [K+]o was evident in the kinetics of IK,out
      activation and deactivation, as well as the steady-state conductance-(g kappa-)
      voltage relations. Linear conductances, determined as a function of the
      conditioning voltage from instantaneous I-V curves, yielded voltages for half
      maximal conductance near -130 mV in 0.1 mM K+, -80 mV in 1.0 mM K+, and -20 mV in
      10 mM K+. Similar data were obtained with Rb+ and Cs+, but not with Na+,
      consistent with the relative efficacy of cation binding under equilibrium
      conditions (K+ > or = Rb+ > Cs+ > > Na+). Changing Ca2+ or Mg2+ concentrations
      outside between 0.1 and 10 mM was without effect on the voltage-dependence of g
      kappa or on IK,out activation kinetics, although 10 mM [Ca2+]o accelerated
      current deactivation at voltages negative of -75 mV. At any one voltage,
      increasing [K+]o suppressed g kappa completely, an action that showed significant
      cooperativity with a Hill coefficient of 2. The apparent affinity for K+ was
      sensitive to voltage, varying from 0.5 to 20 mM with clamp voltages near -100 to
      0 mV, respectively. These, and additional data indicate that extracellular K+
      acts as a ligand and alters the voltage-dependence of IK,out gating; the results
      implicate K(+)-binding sites accessible from the external surface of the
      membrane, deep within the electrical field, but distinct from the channel pore;
      and they are consistent with a serial 4-state reaction-kinetic model for channel
      gating in which binding of two K+ ions outside affects the distribution between
      closed states of the channel.

PMID- 9263887
TI  - Facilitated transport of lactate by rat jejunal enterocyte.
AB  - L-lactate transport mechanism across rat jejunal enterocyte was investigated
      using isolated membrane vesicles. In basolateral membrane vesicles L-lactate
      uptake is stimulated by an inwardly directed H+ gradient; the effect of the pH
      difference is drastically reduced by FCCP, pCMBS and phloretin, while furosemide
      is ineffective. The pH gradient effect is strongly temperature dependent. The
      initial rate of the proton gradient-induced lactate uptake is saturable with
      respect to external lactate with a K(m) of 39.2 +/- 4.8 mM and a Jmax of 8.9 +/-
      0.7 nmoles mg protein-1 sec-1. A very small conductive pathway for L-lactate is
      present in basolateral membranes. In brush border membrane vesicles both Na+ and
      H+ gradients exert a small stimulatory effect on lactate uptake. We conclude that
      rat jejunal basolateral membrane contains a H(+)-lactate cotransporter, whereas
      in the apical membrane both H(+)-lactate and Na(+)-lactate cotransporters are
      present, even if they exhibit a low transport rate.

PMID- 9263888
TI  - Characterization of single inward rectifier potassium channels from embryonic
      Xenopus laevis myocytes.
AB  - Single inward rectifier K+ channels were studied in Xenopus laevis embryonic
      myocytes. We have characterized in detail the channel which is most frequently
      observed (Kir) although we routinely observe three other smaller current levels
      with the properties of inward rectifier K+ channels (Kir(0.3), Kir(0.5) and
      Kir(0.7)). For Kir, slope conductances of inward currents were 10.3, 20.3, and
      27.9 pS, in 60, 120 and 200 mM [K+]o respectively. Extracellular Ba2+ blocked the
      normally high channel activity in a concentration-dependent manner (KA = 7.8
      microM, -90 mV). In whole-cell recordings of inward rectifier K+ current, marked
      voltage dependence of Ba2+ block over the physiological range of potentials was
      observed. We also examined current rectification. Following step depolarizations
      to voltages positive to EK, outward currents through Kir channels were not
      observed even when the cytoplasmic face of excised patches were exposed to Mg(2+)
      free solution at pH 9.1. This was probably also true for Kir(0.3), Kir(0.5) and
      Kir(0.7) channels. We then examined the possibility of modulation of Kir channel
      activity and found neither ATP nor GTP-gamma S had any effect on Kir channel
      activity when added to the solution perfusing the cytoplasmic face of a patch.
      Kinetic analysis revealed Kir channels with a single open state (mean dwell time
      72 msec) and two closed states (time constants 1.4, 79 msec). These results
      suggest that the native Kir channels of Xenopus myocytes have similar properties
      to the cloned strong inward rectifier K+ channels, in terms of conductance,
      kinetics and barium block but does show some differences in the effects of
      modulators of channel activity. Furthermore, skeletal muscle may contain either
      different inward rectifier channels or a single-channel type which can exist in
      stable subconductance states.

PMID- 9263889
TI  - Tonsillectomy: indications for referral by family physicians versus indications
      for surgery by otolaryngologists.
AB  - OBJECTIVE: The purpose of this study was to compare reasons for family physician
      (FP) referral of children for tonsillectomy to the indications for this surgery
      used by otolaryngologists practising in the same region. METHOD: A checklist-type
      survey was sent to a random sample of 300 FPs and all of the practising
      otolaryngologists in Nova Scotia in the spring of 1995. RESULTS: There were
      significant differences between reasons for referral and indications for
      treatment in many areas, the most important of which was that over 60% of FPs
      referred cases because of parental insistence, while no surgeons operated for
      this reason. If inappropriate referrals are taken to be those for which no
      specialist intervention occurs, it appears that there is a significant number of
      referrals. CONCLUSION: These results suggest that both FPs and parents require
      information about these common paediatric problems.

PMID- 9263890
TI  - Is selective neck dissection sufficient treatment for the N0/Np+ neck?
AB  - OBJECTIVE: The purpose of this study was to evaluate the therapeutic role of
      selective neck dissection performed electively in the N0 patient. METHOD: Fifty
      four patients with squamous cell carcinoma of the oral cavity, pharynx, and
      larynx, without clinical evidence of lymph node metastases, underwent 72
      selective neck dissections over a 6-year period. The preoperative tumour and
      patient data were recorded in all patients. Mean follow-up was 59 months. Outcome
      data pertaining to pathologic nodal status, tumour recurrence, and survival were
      recorded on all patients. RESULTS: Eighty-one percent of patients were
      histologically and clinically node negative. Seven percent of N0/Np0 patients
      failed in the neck compared to 50% of patients with occult nodal metastases
      (N0/Np+). Salvage treatment following nodal recurrence was successful in only one
      patient. CONCLUSION: Selective neck dissection does not compromise survival and
      may minimize surgical morbidity in the N0/Np+ population.

PMID- 9263891
TI  - Uvulopalatopharyngoplasty versus laser-assisted uvulopalatopharyngoplasty in the
      treatment of snoring.
AB  - OBJECTIVE: This study was performed to compare the efficacy, pain, and
      complication rates between laser-assisted uvulopalatopharyngoplasty and
      conventional tonsillectomy and uvulopalatopharyngoplasty. METHOD: Eighty patients
      who had undergone the laser procedure and 29 the conventional procedure were
      studied prospectively. Snoring was measured using a new numeric snoring scale.
      RESULTS: There were no statistically significant differences between groups for
      final snoring scores, pain, or complication rates. The criteria for selecting
      uvulopalatopharyngoplasty candidates, which is described, resulted in a 97%
      success rate in the treatment of snoring. CONCLUSION: Laser-assisted
      uvulopalatopharyngoplasty and conventional tonsillectomy and
      uvulopalatopharyngoplasty are equally effective in the management of snoring in
      correctly selected patients. They are similarly painful procedures. A new and
      simple numeric snoring scale is described.

PMID- 9263892
TI  - Paraseptal structural changes and chronic sinus disease in relation to the
      deviated septum.
AB  - OBJECTIVE: This study was conducted to evaluate the use of computerized
      tomography in the delineation of the ostiomeatal complex to enhance the
      endoscopic surgeon's understanding of associated and contributing anatomic
      features. METHODS: The ostiomeatal complex region (OMC) was prospectively
      evaluated in 122 consecutive patients as a function of the degree of nasal-septal
      deviation. This data was correlated with paranasal sinus disease, lateral nasal
      wall findings, and middle-turbinate abnormalities. RESULTS: Patients with
      increasing nasal-septal deviations were associated with a higher incidence of OMC
      obstruction (p < .05). OMC obstruction in the direction of septal angulation was
      attributable to nasal septal deformity. However, contralateral OMC obstruction
      was related to middle-turbinate and lateral nasal-wall abnormalities, which
      appeared with increased frequency on the side opposite to the septal deviation (p
      < .05). Furthermore, an increased incidence and severity of sinus disease was
      noted with increasing septal deviation (p < .05). CONCLUSION: Increasing angles
      of septal deviation are associated with bilateral sinus disease and contralateral
      middle turbinate abnormalities and ethmoid bulla prominence.

PMID- 9263893
TI  - Modified laryngotracheoplasty for surgical management of chronic laryngotracheal
      stenosis in adults.
AB  - A new surgical technique of laryngotracheoplasty with posterior cricoid splitting
      and grafting with thyroid cartilage and long-term stenting was exclusively used
      in 10 patients presenting with laryngotracheal stenosis. The initial results have
      been found to be extremely satisfactory. The surgical method consists of
      meticulous handling of granulation tissue, minimum excision of scar tissue and
      reconstruction of laryngotracheal mucosa and posterior cricoid split with thyroid
      cartilage grafting followed by insertion of a silicone stent in a swiss roll
      fashion. The operative wound at the end is closed in such a fashion that no
      tissue layers are approximated between stent and skin. The clinical picture and
      etiologic aspects of laryngotracheal stenosis are being reviewed.

PMID- 9263895
TI  - Management of head and neck lymphatic malformations in children.
AB  - Lymphatic malformations (LM) are complex entities. Their development and
      management remain controversial. A retrospective review of 35 patients treated
      for lymphatic malformation over a 10-year period (1985-1995) is presented. The
      demographics of the cases, the method of presentation, treatment modalities, and
      outcomes are presented. The majority or patients presented at birth, and 83% were
      treated before the age of 7 years. The most common presentation was an
      asymptomatic neck mass (74%), of which 54% were in the posterior triangle and 17%
      were in the submandibular space. The treatment was primarily surgical excision:
      22 (63%) patients had total surgical excision, 7 (20%) had partial excision, and
      6 (17%) had needle aspiration. A proposal of management is presented.

PMID- 9263894
TI  - Congenital teratomas of the head and neck.
AB  - OBJECTIVE: This article reviews teratomas, neoplasms composed of the three
      germinal layers of the embryo that form tissues foreign to the part in which they
      arise. These are most common in the sacrococcygeal region and are rare in the
      head and neck. In this region, major concerns are airway obstruction and
      cosmesis. METHOD: Pathology records at two tertiary care paediatric hospitals
      were reviewed for diagnoses of head and neck teratomas. This revealed nine cases
      between 1983 and 1993, five males and four females. Two males were stillborn.
      Five were cervical, two were in the nasopharynx, and two were facial. The lesions
      were immature in two cases and mature in the remainder. All of the liveborn
      children underwent surgery within the first year of life, and only one required
      tracheotomy. RESULTS: One child had recurrence of teratomatous tissue diagnosed
      with CT, which was treated surgically. The child has remained free of tumour for
      over 3 years. Pathogenesis, clinical appearance, diagnostic work-up, and
      currently accepted modes of therapy are reviewed.

PMID- 9263896
TI  - Current management of thyroglossal-duct remnant.
AB  - OBJECTIVE: Thyroglossal-duct remnant (TGDR) should be differentiated from ectopic
      thyroid prior to surgical excision. The purpose of this study is to discuss our
      experience with TGDR and review the role of technetium 99m-labelled sodium
      pertechnetate (99mTc), thyroid function test (TFT), ultrasound (US), and
      computerized tomography (CT) scan in the management of TGDR. METHODS AND RESULTS:
      This retrospective study comprised 24 (18 M:6 F) patients with TGDR, whose ages
      ranged between 3 and 52 years, 83.3% of whom were less than 30 years of age. The
      most common complaints were anterior neck swelling in 79% (19/24) and draining
      sinus in 37.5% (9/24). Other rare complaints include throat discomfort,
      hoarseness, and pain. Axial CT scan through the area of interest in four patients
      revealed intralaryngeal and extralaryngeal extension, with some cartilage
      destruction and pre-epiglottic extension in two patients. 99mTc and US and TFT
      demonstrated normal thyroid in 11 and 10 patient, respectively. Thyroid tissue
      element reported histologically in 58.3% (14/24) of cases. These 24 patients
      underwent 10 simple cyst excisions and 21 Sistrunk procedures. The rate of
      recurrence was 40% and 7%, respectively. CONCLUSION: When the thyroid gland can
      be identified in the normal position, coexistent ectopic thyroid is seldom found.
      However, when ectopic thyroid is suspected, 99mTc and TFT are valuable tests.
      Furthermore, CT scan may be profitable when there is evidence of laryngeal
      involvement. Sistrunk's procedure replaces simple cyst excision and continues to
      be the mainstay treatment of TGDR.

PMID- 9263897
TI  - Invasive Aspergillus tympanomastoiditis in an immunocompetent patient.

PMID- 9263898
TI  - Congenital mesenchymoma transgressing the cribriform plate.

PMID- 9263899
TI  - Botulinum toxin for cricopharyngeal dysphagia: case reports of CT-guided
      injection.
AB  - OBJECTIVE: The National Institutes of Health have recognized the use of botulinum
      toxin (Botox) as a therapeutic agent to treat many ophthalmologic and
      otolaryngologic disorders. There are three reports in the literature regarding
      the use of Botox to treat cricopharyngeal dysphagia, all describing good results.
      In the larger study, the toxin was administered under general anaesthetic. This
      article discusses CT-guided injection of Botox: a relatively noninvasive, out
      patient procedure. We also discuss failure of injection in one case and
      complications in another. CONCLUSION: The patients described experienced
      improvement in their dysphagia symptoms following injection.

PMID- 9263900
TI  - Hemangiopericytoma of the sinonasal tract.

PMID- 9263902
TI  - How we do it: diathermy palatoplasty.

PMID- 9263901
TI  - Relief of sensorineural hearing loss due to rheumatoid arthritis by endolymphatic
      sac decompression.

PMID- 9263903
TI  - How we do it: management of facial hyperpigmentation.

PMID- 9263904
TI  - The history of otolaryngology in Canada: University of Ottawa.

PMID- 9263905
TI  - The history of otolaryngology in Canada: University of Sherbrooke.

PMID- 9263906
TI  - Extracellular divalent cations block a cation non-selective conductance unrelated
      to calcium channels in rat cardiac muscle.
AB  - 1. The effect of removing extracellular divalent cations on resting potential
      (Vrest) and background conductance of rat cardiac muscle was studied. Vrest was
      measured with 3 M KCl-filled microelectrodes in papillary muscles, or with a
      patch electrode in ventricular myocytes. Whole-cell membrane currents were
      measured in myocytes using step or ramp voltage commands. 2. In both muscles and
      single cells, decrease or removal of Ca2+o and Mg2+o caused a nifedipine
      resistant depolarization, which was reversed upon readmission of Ca2+o or Mg2+o
      (half-maximal effect at 0.8 mM Ca2+o or 3 mM Mg2+o in muscles). 3. In single
      myocytes, removal of Ca2+o and Mg2+o had no effect on the seal resistance in
      nonruptured cell-attached recordings, but reversibly induced a current with a
      reversal potential (Vrev) of -8 +/- 3.4 mV (with internal Cs+; mean +/- S.E.M., n
      = 23) during whole-cell recordings. The current was insensitive to nifedipine (3
      100 microM) or amiloride (1 mM). Vrev was insensitive to changes in the
      equilibrium potential for chloride ions (ECl). 4. The current induced in the
      absence of extracellular divalent cations was blocked in a concentration
      dependent manner by Ca2+o. (At -80 mV, the affinity constant KCa was 60 microM
      with a Hill coefficient of 0.9) KCa was voltage dependent at positive but not
      negative potentials. Mg2+o, Ni2+o, Sr2+o, Ba2+o, Cd2+o and Gd3+o also blocked the
      current. 5. In 0 mM Na+ (145 mM NMDG+), the inward component of the divalent
      cation-sensitive current was decreased and Vrev shifted to more negative
      potentials. 6. These results suggest that a novel conductance pathway, permeable
      to monovalent cations but not to Cl- and blocked by divalent cations, exists in
      ventricular myocytes.

PMID- 9263907
TI  - P-glycoprotein is not a swelling-activated Cl- channel; possible role as a Cl-
      channel regulator.
AB  - 1. The whole-cell configuration of the patch-clamp technique was used to
      determine if P-glycoprotein (Pgp) is a swelling-activated Cl- channel. 2. Hamster
      pgp1 cDNA was transfected into a mouse fibroblast cell line resulting in
      expression of functional Pgp in the plasma membrane. This cell line was obtained
      without exposure to chemotherapeutic agents. 3. Swelling-activated whole-cell Cl-
      current (ICl,swell) was elicited by lowering the bath osmolality. ICl,swell was
      characterized in detail in the pgp1-transfected mouse cell line and compared with
      that of its parental cell line. Expression of Pgp did not modify the magnitude or
      properties of ICl,swell, except that addition of the anti-Pgp antibody C219 to
      the pipette solution inhibited this current by 75% only in the Pgp-expressing
      cells. 4. ICl,swell in the mouse Pgp-expressing cell line was compared with that
      in a Pgp-expressing hamster fibroblast cell line. The characteristics of
      ICl,swell (voltage dependence, blocker sensitivity, anion selectivity sequence,
      requirement for hydrolysable ATP) in Pgp-expressing cells were different between
      the two cell lines. These results suggest that the channel(s) responsible for
      ICl,swell are different between the two cell lines. In addition, C219 inhibited
      ICl,swell in both Pgp-expressing cell lines, even though they seem to express
      different swelling-activated Cl- channels. 5. We conclude that firstly, Pgp is
      not a swelling-activated Cl- channel; secondly, it possibly functions as a Cl-
      channel regulator; and thirdly, ICl,swell is underlined by different Cl- channels
      in different cells.

PMID- 9263908
TI  - Chloride channel blockers inhibit myogenic tone in rat cerebral arteries.
AB  - 1. We have investigated the role of chloride channels in pressure-induced
      depolarization and contraction of cerebral artery smooth muscle cells. 2. Two
      chloride channel blockers, indanyloxyacetic acid (IAA-94) and 4,4'
      diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS), caused hyperpolarizations
      (10-15 mV) and dilatations (up to 90%) of pressurized (80 mmHg), rat posterior
      cerebral arteries. Niflumic acid, a blocker of calcium-activated chloride
      channels, did not affect arterial tone. 3. Dilatations to IAA-94 and DIDS were
      unaffected by potassium channel blockers, but were prevented by elevated
      potassium. IAA-94 and DIDS had no effect on membrane potential or diameter of
      arteries at low intravascular pressure, where myogenic tone is absent. Reduction
      of extracellular chloride (60 mM Cl-) increased the pressure-induced
      contractions. Removal of extracellular sodium did not affect the pressure-induced
      responses. 4. Our results suggest that intravascular pressure activates DIDS- and
      IAA-94-sensitive chloride channels to depolarize arterial smooth muscle, thereby
      contributing to the myogenic constriction.

PMID- 9263909
TI  - Corticotropin releasing hormone inhibits an inwardly rectifying potassium current
      in rat corticotropes.
AB  - 1. The perforated-patch-clamp technique was used to identify an inwardly
      rectifying K+ current (IK(IR)) in cultured rat anterior pituitary cells highly
      enriched in corticotropes. IK(IR) was rapidly activating and highly selective for
      K+. The K+ conductance was approximately proportional to the square root of the
      extracellular K+ concentration. 2. IK(IR) was blocked in a voltage-dependent
      manner by external Ba2+ and Cs+, slightly attenuated by 5 mM 4-aminopyridine (15%
      inhibition) and insensitive to 10 mM tetraethylammonium, 2 mM Ca2+, 1 mM Cd2+ and
      50 microM La3+. 3. In physiological saline, 100 microM Ba2+, which inhibits 86%
      of IK(IR) at the cell resting potential, depolarized cells by 6.1 +/- 0.7 mV from
      a mean resting potential of -59.6 +/- 0.8 mV. 4. Corticotropin releasing hormone
      (CRH), which activates adenylyl cyclase and stimulates adrenocorticotropic
      hormone (ACTH) secretion from corticotropes, inhibited IK(IR) by 25% and
      depolarized the cells by 10.2 +/- 1.0 mV. Dibutyryl cAMP ((Bu)2cAMP) mimicked
      these effects. 5. The membrane depolarization evoked by Ba2+ or CRH increased the
      cell firing frequency. Comparison of cells exhibiting a membrane potential of
      approximately -50 mV revealed that spike frequency in the presence of CRH (109 +/
      7 spikes (5 min)-1) was greater than in control (60 +/- 5 spikes (5 min)-1) or
      Ba(2+)-treated (77 +/- 15 spikes (5 min)-1) corticotropes. 6. The data suggest
      that IK(IR) contributes to maintenance of the resting membrane potential of rat
      corticotropes. Inhibition of IK(IR) plays a role in, but does not account for all
      of, the membrane depolarization and enhancement of firing frequency evoked by
      CRH.

PMID- 9263910
TI  - Interactions between neuropeptide Y and the adenylate cyclase pathway in rat
      mesenteric small arteries: role of membrane potential.
AB  - 1. Simultaneous measurements of membrane potential and tension were performed to
      investigate the intracellular mechanisms of neuropeptide Y (NPY) in rat
      mesenteric small arteries. 2. NPY (0.1 microM) depolarized arterial smooth muscle
      cells from -55 to -47 mV and increased wall tension by 0.22 N m-1, representing
      11% of the contraction elicited by a high-potassium solution. Isoprenaline (1
      microM) and acetylcholine (1 microM) evoked hyperpolarizations of 11 and 17 mV,
      respectively. NPY inhibited the isoprenaline-induced effects on membrane
      potential without affecting those of acetylcholine. 3. Forskolin evoked sustained
      concentration-dependent hyperpolarizations of small mesenteric arteries. NPY (0.1
      microM) inhibited the responses to 1 microM forskolin, but did not alter the
      stable hyperpolarization elicited by the specific activator of protein kinase A
      (PKA) SP-5,6-DCl-cBIMPS (0.1 mM). Forskolin increased the cyclic AMP (cAMP)
      content of the arteries 21-fold, and NPY inhibited the forskolin-evoked increase
      in cAMP levels by 91%. 4. The hyperpolarization produced by 1 microM forskolin
      was not affected by either charybdotoxin (0.1 microM) or 4-aminopyridine (0.5
      mM), but glibenclamide (5 microM) inhibited the hyperpolarization by 70%.
      Glibenclamide also inhibited the hyperpolarization evoked by SP-5,6-DCl-cBIMPS by
      59%. 5. Neither depolarization nor contraction caused by NPY were significantly
      affected by either glibenclamide (5 microM) or nifedipine (1 microM), but they
      were reduced by gadolinium (10 microM). However, the blocking effect of NPY on
      forskolin-elicited hyperpolarization was not affected by gadolinium. 6.
      Charybdotoxin (0.1 microM) and 4-aminopyridine (0.5 mM) strongly enhanced the
      depolarization and contraction caused by NPY (0.1 microM), and nifedipine (1
      microM) prevented the enhanced responses to NPY in the presence of charybdotoxin.
      7. These findings suggest that NPY acts through at least two different
      intracellular mechanisms in mesenteric small arteries: a depolarization of
      arterial smooth muscle which is probably due to activation of non-selective
      cation channels, and a marked inhibition of adenylate cyclase activity, which in
      turn inhibits the hyperpolarization produced by cAMP accumulation in these
      arteries.

PMID- 9263911
TI  - Selective inhibition of a slow-inactivating voltage-dependent K+ channel in rat
      PC12 cells by hypoxia.
AB  - 1. Electrophysiological (single-channel patch clamp) and molecular biological
      experiments (reverse transcriptase-polymerase chain reaction) were performed to
      attempt to identify the O2-sensitive K+ channel in rat phaeochromocytoma (PC12)
      cells. 2. Four types of K+ channels were recorded in PC12 cells: a small
      conductance K+ channel (14 pS), a calcium-activated K+ channel (KCa; 102 pS) and
      two K+ channels with similar conductance (20 pS). These last two channels
      differed in their time-dependent inactivation: one was a slow-inactivating
      channel, while the other belonged to the family of fast transient K+ channels. 3.
      The slow-inactivating 20 pS K+ channel was inhibited by hypoxia. Exposure to
      hypoxia produced a 50% reduction in channel activity (number of active channels
      in the patch x open probability). Hypoxia had no effect on the 20 pS transient K+
      channels, whereas reduced O2 stimulated the KCa channels. 4. The genes encoding
      the alpha-subunits of slow-inactivating K+ channels for two members of the Shaker
      subfamily of K+ channels (Kv1.2 and Kv1.3) together with the Kv2.1, Kv3.1 and
      Kv3.2 channel genes were identified in PC12 cells. 5. The expression of the
      Shaker Kv1.2, but none of the other K+ channel genes, increased in cells exposed
      to prolonged hypoxia (18 h). The same cells were more responsive to a subsequent
      exposure to hypoxia (35% inhibition of K+ current measured in whole-cell voltage
      clamp) compared with the cells maintained in normoxia (19% inhibition). 6. These
      results indicate that the O2-sensitive K+ channel in PC12 cells is a 20 pS slow
      inactivating K+ channel that is upregulated by hypoxia. This channel appears to
      belong to the Shaker subfamily of voltage-gated K+ channels.

PMID- 9263912
TI  - Voltage-dependent binding and calcium channel current inhibition by an anti-alpha
      1D subunit antibody in rat dorsal root ganglion neurones and guinea-pig myocytes.
AB  - 1. The presence of calcium channel alpha 1D subunit mRNA in cultured rat dorsal
      root ganglion (DRG) neurones and guinea-pig cardiac myocytes was demonstrated
      using the reverse transcriptase-polymerase chain reaction. 2. An antipeptide
      antibody targeted at a region of the voltage-dependent calcium channel alpha 1D
      subunit C-terminal to the pore-forming SS1-SS2 loop in domain IV (amino acids
      1417-1434) only bound to this exofacial epitope if the DRG neurones and cardiac
      myocytes were depolarized with 30 mM K+. 3. Incubation of cells under
      depolarizing conditions for 2-4 h with the antibody resulted in a maximal
      inhibition of inward current density of 49% (P < 0.005) for DRGs and 30% (P <
      0.05) for cardiac myocytes when compared with controls. 4. S-(-)-Bay K 8644 (1
      microM) enhanced calcium channel currents in DRGs by 75 +/- 19% (n = 5) in
      neurones incubated under depolarizing conditions with antibody that had been
      preabsorbed with its immunizing peptide (100 micrograms ml-1). This was
      significantly (P < 0.05) larger than the enhancement by S-(-)-Bay K 8644 that was
      seen with cells incubated under identical conditions but with antibody alone,
      which was 15 +/- 4% (n = 5). 5. These results demonstrate the presence of calcium
      channel alpha 1D subunits in rat DRG neurones and guinea-pig cardiac myocytes.
      They also show that amino acids 1417-1434 of the alpha 1D subunit are only
      exposed to the extracellular face of the membrane following depolarization and
      that the binding of an antibody to these amino acids attenuates calcium channel
      current and reduces the ability of S-(-)-Bay K 8644 to enhance this current,
      indicating that it is an L-type current that is attenuated.

PMID- 9263913
TI  - Receptors couple to L-type calcium channels via distinct Go proteins in rat
      neuroendocrine cell lines.
AB  - 1. The present study examines the hypothesis of G protein subtype selectivity in
      receptor-induced inhibition of calcium channel currents (ICa) in the insulin
      secreting RINm5F and pituitary GH3 rat cell lines. Specificity of receptor
      coupling to G proteins was studied by infusion of purified G alpha isoforms into
      cells via a patch pipette. 2. In RINm5F cells, the neuropeptide galanin inhibited
      dihydropyridine (DHP)- and omega-conotoxin-sensitive components of ICa and slowed
      down their activation kinetics. In GH3 cells, DHP-sensitive ICa was inhibited by
      galanin, as well as by somatostatin and carbachol. Agonist-induced ICa inhibition
      was suppressed by pertussis toxin (PTX) pretreatment of the cells. In PTX
      pretreated cells of either cell line, the response to galanin was restored only
      by the G alpha o1 subunit. Following PTX treatment of GH3 cells, only the G alpha
      o1 subunit restored carbachol-induced inhibition of ICa, whereas only the G alpha
      o2 subunit restored somatostatin-induced inhibition of ICa. G(i) subtypes had no
      effect on ICa inhibition. 3. Both cell lines expressed two distinct
      immunoreactive Go proteins. Whereas in RINm5F cell membranes Go1 was found to be
      the predominant isoform, we detected more Go2 than Go1 in GH3 cell membranes.
      Nevertheless, all agonists stimulated incorporation of the photoreactive GTP
      analogue [alpha-32P]GTP azidoanilide into both G(o) isoforms. 4. The results
      indicate that the same Go subtype, i.e. Go1, mediates galanin-induced inhibition
      of ICa in both cell lines and that the Go subtype specificity of receptor-G
      protein coupling is confined to intact cells.

PMID- 9263914
TI  - Currents evoked in Bergmann glial cells by parallel fibre stimulation in rat
      cerebellar slices.
AB  - 1. Whole-cell recordings were obtained from Bergmann glial cells in rat
      cerebellar slices. 2. The cells had low input resistances (70 +/- 38 M omega; n =
      13) and a mean resting potential of -82 +/- 6 mV (n = 12) with a potassium-based
      internal solution. Electrical and dye coupling between Bergmann glia were
      confirmed. 3. Stimulation of parallel fibres induced a complex, mostly inward
      current which could be decomposed pharmacologically. 4. The ionotropic glutamate
      receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM), but
      not DL-2-amino-5-phosphonopentanoic acid (DL-APV; 100 microM) consistently
      blocked an early inward current component that may reflect synaptic activation of
      AMPA/kainate receptors in Bergmann glia. 5. Addition of cadmium ions (100 microM)
      to inhibit transmitter release blocked most of the CNQX-APV-insensitive current.
      This component probably reflects electrogenic uptake of the synaptically released
      glutamate. 6. Tetrodotoxin (TTX; 1 microM) blocked the remaining inward current:
      a slow component, possibly produced by the potassium ion efflux during action
      potential propagation in parallel fibres. An initial triphasic component of the
      response was also TTX sensitive and reflected passage of the parallel fibre
      action potential volley. 7. The putative glutamate uptake current was further
      characterized; it was blocked by the competitive uptake blockers D-aspartate (0.5
      mM) and L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC; 0.5 mM), and by
      replacement of sodium with lithium. Monitoring the triphasic TTX-sensitive
      component showed that this inhibition did not result from changes of action
      potential excitation and propagation. 8. Intracellular nitrate ions increased the
      putative uptake current, consistent with the effect of this anion on glutamate
      transporters. 9. The putative uptake current was reduced by depolarization,
      consistent with the voltage dependence of glutamate uptake. 10. It is concluded
      that a large fraction of the current induced by parallel fibre stimulation
      reflects the uptake of synaptically released glutamate. The uptake current
      activated rapidly, with a 20-80% rise time of 2.3 +/- 0.7 ms (n = 10), and
      decayed with a principal time constant of 25 +/- 6 ms (n = 10).

PMID- 9263915
TI  - Role of Q-type Ca2+ channels in vasopressin secretion from neurohypophysial
      terminals of the rat.
AB  - 1. The nerve endings of rat neurohypophyses were acutely dissociated and a
      combination of pharmacological, biophysical and biochemical techniques was used
      to determine which classes of Ca2+ channels on these central nervous system (CNS)
      terminals contribute functionally to arginine vasopressin (AVP) and oxytocin (OT)
      secretion. 2. Purified neurohypophysial plasma membranes not only had a single
      high-affinity binding site for the N-channel-specific omega-conopeptide MVIIA,
      but also a distinct high-affinity site for another omega-conopeptide (MVIIC),
      which affects both N- and P/Q-channels. 3. Neurohypophysial terminals exhibited,
      besides L- and N-type currents, another component of the Ca2+ current that was
      only blocked by low concentrations of MVIIC or by high concentrations of omega
      AgaIVA, a P/Q-channel-selective spider toxin. 4. This Ca2+ current component had
      pharmacological and biophysical properties similar to those described for the
      fast-inactivating form of the P/Q-channel class, suggesting that in the
      neurohypophysial terminals this current is mediated by a 'Q'-type channel. 5.
      Pharmacological additivity studies showed that this Q-component contributed to
      rises in intraterminal Ca2+ concentration ([Ca2+]i) in only half of the terminals
      tested. 6. Furthermore, the non-L- and non-N-component of Ca(2+)-dependent AVP
      release, but not OT release, was effectively abolished by the same blockers of Q
      type current. 7. Thus Q-channels are present on a subset of the neurohypophysial
      terminals where, in combination with N- and L-channels, they control AVP but not
      OT peptide neurosecretion.

PMID- 9263916
TI  - Calcium release from intracellular stores evoked by extracellular ATP in a
      Xenopus renal epithelial cell line.
AB  - 1. The signal transduction mechanism mediating extracellular adenosine 5'
      triphosphate (ATP)-induced calcium release in a renal epithelial cell line (A6)
      was investigated using the whole-cell voltage-clamp technique and fura-2
      fluorescence measurement. 2. ATP (10 microM) activated calcium-dependent non
      selective cation channels in cells held under voltage clamp. 3. Guanosine 5'-O-(2
      thiodiphosphate) (GDP beta S; 0.1-1.0 mM) in the pipette inhibited the ATP
      activated calcium-dependent currents. With guanosine 5'-O-(3-thiotriphosphate)
      (GTP gamma S; 0.1-1.0 mM) in the pipette, the currents were spontaneously
      elicited without application of ATP. Pretreatment with pertussis toxin (PTX)
      affected neither the ATP-activated currents nor the increase in intracellular
      free calcium concentration ([Ca2+]i) evoked by ATP. 4. Intracellular application
      of neomycin or heparin inhibited the ATP-activated currents. Inositol 1,4,5
      trisphosphate (IP3; 0.1-100 microM) in the internal solution produced currents
      similar to those due to ATP activation. 5. These results suggest that a PTX
      insensitive guanosine 5'-triphosphate (GTP)-binding regulatory protein (G.
      protein) is involved in extracellular. ATP-induced phosphoinositide turnover and
      subsequent calcium release from IP3-sensitive stores, which subsequently
      activates the calcium-dependent channels in A6 cells.

PMID- 9263917
TI  - The electrogenic effects of Na(+)-K(+)-ATPase in rat auditory thalamus.
AB  - 1. The electrogenic effects of the Na(+)-K(+)-ATPase in thalamic neurones were
      investigated by means of intracellular and whole-cell patch-clamp recording
      techniques in rat medial geniculate body (MGB) maintained in vitro. 2. In twenty
      six out of thirty-one neurones recorded intracellularly, application of the Na(+)
      K+ pump inhibitor strophanthidin induced two different types of membrane
      depolarization: a small, reversible depolarization with a peak amplitude of 4 +/-
      2.6 mV or a prolonged depolarization of large amplitude (48.6 +/- 9.0 mV) with or
      without a decrease in apparent membrane resistance. Blockade of glutamate
      receptors with kynurenic acid or 6-cyano-7-nitroquinoxaline-2,3-dione and (+/-)-2
      amino-5-phosphonopentanoic acid did not prevent either type of pump response, but
      the large depolarization was not seen when the medium contained the sodium
      channel blocker TTX. 3. Whole-cell patch-clamp recording showed that the small
      membrane depolarization is mediated by an inward membrane current (39.00 +/- 5.70
      pA) that exhibited a weak voltage dependence. An inward current of similar
      amplitude was also induced in MGB cells when the pipette solution contained
      nominally zero Na+ or when K+ was temporarily omitted from the extracellular
      medium. The large membrane depolarization or the corresponding membrane current
      was not observed in whole-cell conditions. 6. Transient inhibition of the
      electrogenic Na(+)-K(+)-ATPase consistently led to a change in the mode of
      synaptic transmission in MGB cells, during which the synaptically evoked burst
      response was either blocked or converted into a single spike discharge. 7. Taken
      together, these data suggest that blockade of the electrogenic pump produces a
      dual membrane effect in mammalian thalamic neurones: a small electrogenic
      membrane depolarization and a large depolarization response that can be prevented
      by artificially maintaining the transmembrane ionic gradients. The electrogenic
      activity of the Na(+)-K(+)-ATPase may play an important role in setting the mode
      of synaptic transmission in sensory thalamus.

PMID- 9263918
TI  - Differential Na(+)-K(+)-ATPase activity in rat lemniscal and non-lemniscal
      auditory thalami.
AB  - 1. Using whole-cell recording and confocal immunofluorescent microscopy, we have
      investigated the differential electrogenic activity, subunit expression and
      subcellular distribution of the Na(+)-K(+)-ATPase in the lemniscal (ventral) and
      non-lemniscal (dorsal) pathways of the rat medial geniculate body (MGB) in vitro.
      2. Bath application of Na(+)-K(+)-ATPase inhibitors strophanthidin or dihydro
      ouabain produced a transient, dose-dependent inward current or membrane
      depolarization which were significantly larger in dorsal MGB neurones than in
      ventral cells (45.9 +/- 6.45 vs. 24.3 +/- 4.1 pA; P < 0.05). Electrophysiological
      and morphometric measurements showed that the dorsal MGB neurones had a
      significantly lower input conductance and a smaller somata than their ventral
      counterparts. The level of the resting membrane potential also differed by about
      6 mV between the two cell populations, with the dorsal cells being more
      hyperpolarized (-74.2 +/- 0.6 vs. -67.7 +/- 1.3 mV; P < 0.001). 3. Incubation of
      enzymatically dissociated MGB neurones with fluorescent monoclonal antibodies
      against alpha 1-alpha 3 isoforms of Na(+)-K(+)-ATPase showed that both dorsal and
      ventral cells expressed primarily alpha 3 subunits. Confocal laser scanning
      revealed, however, that the mean pixel density of alpha 3 fluorescent antibodies
      in the plasma membrane domain, but not in the cytoplasmic compartment, was about
      40% higher in dorsal neurones than in the ventral cells (29.7 +/- 4.7 vs. 16.9 +/
      2.3 grey shadow per pixel; P < 0.05). 4. The above results suggest that the
      electrogenic activity of the Na(+)-K(+)-ATPase is differentially regulated
      between lemniscal and non-lemniscal auditory thalami through a mechanism that
      probably involves differential pump densities in the cell membrane.

PMID- 9263919
TI  - Hyperpolarization of isolated capillaries from guinea-pig heart induced by K+
      channel openers and glucose deprivation.
AB  - 1. The present study was designed to test if microvascular coronary endothelial
      cells express ATP-sensitive K+ channels (KATP channels). We performed
      microfluorometric measurements of the membrane potential of freshly isolated
      guinea-pig coronary capillaries equilibrated with the voltage-sensitive dye bis
      oxonol (bis-[1,3-dibutylbarbituric acid] trimethineoxonol, [DiBAC4(3)]). 2. The
      resting membrane potential of capillaries in physiological salt solution was -46
      +/- 4.2 mV (n = 8) at room temperature (22 degrees C) as determined after
      calibration of the fluorescence using the Na(+)-K+ ionophore gramicidin in the
      presence of different K+ concentrations. Spontaneous membrane potential
      fluctuations of 10-20 mV amplitude were often observed. 3. A reversible,
      sustained hyperpolarization to a new membrane potential close to the K+
      equilibrium potential (EK) could be induced by application of the K+ channel
      openers HOE 234 (100 nM to 1 microM), diazoxide (10 PM to 100 nM) or pinacidil
      (100 nM). Subsequent addition of glibenclamide (200 nM to 2 microM) reversed this
      hyperpolarization. 4. A glibenclamide-sensitive hyperpolarization of coronary
      capillaries to values near EK was also observed upon omission of D-glucose (10
      mM) from the superfusing solution or by substituting L-glucose for D-glucose.
      Maximum hyperpolarization was reached in less than 10 min. 5. Our results suggest
      that microvascular coronary endothelial cells express KATP channels which may be
      activated during hypoglycaemia.

PMID- 9263920
TI  - Regulation by gastric acid of the processing of progastrin-derived peptides in
      rat antral mucosa.
AB  - 1. Inhibition of gastric acid secretion by proton pump inhibitors like omeprazole
      increases the synthesis and secretion of the pyloric antral hormone gastrin. We
      report here how omeprazole influences the conversion of the gastrin precursor to
      its final products, and the abundance of mRNAs encoding proteins associated with
      progastrin processing in rat antral mucosa. 2. Progastrin processing was studied
      using a pulse-chase protocol in antral mucosa, incubated in vitro, from rats
      treated with omeprazole for up to 5 days. Labelled peptides were detected by on
      line scintillation counting after immunoprecipitation and HPLC. The mRNAs
      encoding prohormone-processing enzymes were identified by Northern blot,
      polymerase chain reaction or ribonuclease protection assay, and their cellular
      origins identified by immunocytochemistry. 3. Cleavage of [3H]- and [35S]
      labelled progastrins at Arg-94-95 or Arg-57-58, and amidation at Phe-92 were not
      influenced by pretreatment with omeprazole. In contrast, cleavage of G34 (the
      thirty-four amino acid amidated gastrin) at Lys-74-75 to give G17 (the seventeen
      amino acid amidated gastrin), and of G34-Gly to G17-Gly (G34 and G17 with COOH
      terminal glycine), was increased 3-fold after treatment with omeprazole for
      either 1 or 5 days. 4. Approximately 20% of newly synthesized amidated and Gly
      extended gastrins were secreted within 240 min of the labelling period in
      omeprazole-treated samples, but secretion of labelled gastrins from control
      tissue was undetectable over a comparable period. 5. The amidating enzyme,
      peptidyglycine alpha-amidating mono-oxygenase (PAM), the prohormone convertases
      PC1/3, PC2, PC5 and the PC2 chaperone 7B2 were localized to rat antral gastrin
      cells by immunocytochemistry. The relative abundance of mRNA species encoding
      7B2, PC5 and PAM were unchanged after treatment with omeprazole for 5 days,
      whereas gastrin, PC1/3 and PC2 mRNAs are known to increase at this time. 6. The
      main consequence of increased cleavage at Lys-74-75 is the production of G17 and
      G17-Gly at the expense of G34 and G34-Gly, respectively. The latter have longer
      plasma half-lives, and so their increased cleavage may serve to limit the rise in
      plasma gastrin concentration after inhibition of acid secretion. Changes in the
      abundance of mRNAs encoding prohormone-processing enzymes cannot account for the
      rapidity of the changes in cleavage of progastrin at Lys residues after
      omeprazole.

PMID- 9263921
TI  - Mechanisms for stimulation of rat anterior pituitary cells by arginine and other
      amino acids.
AB  - 1. Arginine and other amino acids are secretagogues for growth hormone and
      prolactin in the intact animal, but the mechanism of action is unclear. We have
      studied the effects of amino acids on cytosolic free calcium concentration
      ([Ca2+]i) in single rat anterior pituitary (AP) cells. Arginine elicited a large
      increase of [Ca2+]i) in about 40% of all the AP cells, suggesting that amino
      acids may modulate hormone secretion by acting directly on the pituitary. 2. Cell
      typing by immunofluorescence of the hormone the cells store showed that the
      arginine-sensitive cells are distributed uniformly within all the five AP cell
      types. The arginine-sensitive cells overlapped closely with the subpopulation of
      cells sensitive to thyrotrophin-releasing hormone. 3. Other cationic as well as
      several neutral (dipolar) amino acids had the same effect as arginine. The
      increase of [Ca2+]i was dependent on extracellular Ca2+ and blocked by
      dihydropyridine, suggesting that it is due to Ca2+ influx through L-type voltage
      gated Ca2+ channels. The [Ca2+]i increase was also blocked by removal of
      extracellular Na+ but not by tetrodotoxin. The substrate specificity for
      stimulation of AP cells resembled closely that of the amino acid transport system
      B0+. We propose that electrogenic amino acid influx through this pathway
      depolarizes the plasma membrane with the subsequent activation of voltage-gated
      Ca2+ channels and Ca2+ entry. 4. Amino acids also stimulated prolactin secretion
      in vitro with a similar substrate specificity to that found for the [Ca2+]i
      increase. Existing data on the stimulation of secretion of other hormones by
      amino acids suggest that a similar mechanism could apply to other endocrine
      glands.

PMID- 9263922
TI  - Mechanical study of rat soleus muscle using caged ATP and X-ray diffraction: high
      ADP affinity of slow cross-bridges.
AB  - 1. The cross-bridges in slow- and fast-twitch fibres (taken, respectively, from
      soleus and psoas muscles of rats) were examined in mechanical experiments using
      caged ATP and X-ray diffraction, to compare their binding of ATP and ADP. 2.
      Caged ATP was photolysed in rigor fibres. When ADP was removed from pre
      photolysis fibres, the initial relaxation (+/- Ca2+) in soleus was as fast as
      that in psoas fibres, whereas the subsequent contraction (+Ca2+) was slower in
      soleus than in psoas. The ATPase rate during the steady-state contraction was
      also slower in soleus fibres. 3. When ADP was added to pre-photolysis fibres (+/-
      Ca2+), tension developed even in the initial phase, the overall tension
      development being biphasic. Both initial and late components of the Ca(2+)-free
      contraction were enhanced when ADP was added before photolysis, although pre
      photolysis ADP was not a prerequisite for the late component. The effect of ADP
      was greater in soleus than in psoas fibres. Static experiments on rigor fibres
      revealed a higher ADP affinity in soleus fibres. 4. The intensity of the actin
      layer-line from ADP rigor soleus fibres decreased rapidly on photorelease of ATP.
      We conclude that, despite the tight ADP binding of the soleus cross-bridge, its
      isometric reaction is not rate limited by the 'off' rate of ADP.

PMID- 9263924
TI  - Reflex cardiac dromotropic responses to stimulation of the carotid and aortic
      chemoreceptors in the anaesthetized cat.
AB  - 1. The reflex changes in the dromotropic state of the heart (P-R interval or
      atrioventricular conduction time) in response to selective stimulation of the
      carotid and aortic bodies by sodium cyanide were studied in the anaesthetized
      cat. The heart was paced and the arterial blood pressure was kept constant to
      minimize secondary effects of changes in arterial baroreceptor activity. 2.
      Stimulation of the carotid and aortic bodies caused an increase in the
      atrioventricular conduction time. 3. Evidence is presented to suggest that this
      negative dromotropic response was due predominantly to a vagal cholinergic
      mechanism. There is a small sympathetic component but only in so far as the
      carotid body reflex is concerned. 4. The negative dromotropic responses were
      enhanced during reflex suppression of the central inspiratory neuronal drive
      combined with minimal activity of the slowly adapting pulmonary stretch afferents
      indicating that they are respiratory modulated. 5. The clinical implications of
      these results are discussed.

PMID- 9263925
TI  - Stress in the workplace: unfinished business.

PMID- 9263923
TI  - Chemo-mechanical energy transduction in relation to myosin isoform composition in
      skeletal muscle fibres of the rat.
AB  - 1. ATP consumption and force development were determined in single skinned muscle
      fibres of the rat at 12 degrees C. Myofibrillar ATPase consumption was measured
      photometrically from NADH oxidation which was coupled to ATP hydrolysis. Myosin
      heavy chain (MHC) and light chain (MLC) isoforms were identified by gel
      electrophoresis. 2. Slow fibres (n = 14) containing MHCI and fast fibres (n = 18)
      containing MHCIIB were compared. Maximum shortening velocity was 1.02 +/- 0.63
      and 3.05 +/- 0.23 lengths s-1, maximum power was 1.47 +/- 0.22 and 9.59 +/- 0.84
      W l-1, and isometric ATPase activity was 0.034 +/- 0.003 and 0.25 +/- 0.01 mM s-1
      in slow and in fast fibres, respectively. 3. In fast as well as in slow fibres
      ATP consumption during shortening increased above isometric ATP consumption. The
      increase was much greater in fast fibres than in slow fibres, but became similar
      when expressed relative to the isometric ATPase rate. 4. Efficiency was
      calculated from mechanical power and free energy change associated with ATP
      hydrolysis. Maximum efficiency was larger in slow than in fast fibres (0.38 +/-
      0.04 versus 0.28 +/- 0.03) and was reached at a lower shortening velocity. 5.
      Within the group of fast fibres efficiency was lower in fibres which contained
      more MLC3f. We conclude that both MHC and essential MLC isoforms contribute to
      determine efficiency of chemo-mechanical transduction.

PMID- 9263926
TI  - An intervention strategy for workplace stress.
AB  - This article explores a range of sources of workplace stress and a three-prong
      intervention strategy for managing pressures at work. The three approaches
      highlighted are primary, secondary, and tertiary prevention interventions.
      Primary is concerned with stressor reduction, secondary with stress management
      and tertiary with remedial support. In addition, a number of wider policy issues
      are suggested, such as risk assessment, economic incentives, and specific
      measures to help small- and medium-sized workplaces in managing workplace stress.

PMID- 9263927
TI  - Upper limb disorders and work: the importance of physical and psychosocial
      factors.
AB  - Upper limb, shoulder, and neck disorders cause both acute and chronic pain, as
      well as significant functional impairment. They impose a heavy financial burden
      on societies, industries, and individuals. Our understanding of the pathology of
      many of the disorders is poor. The epidemiological pursuit of causal
      relationships is hampered by the nature of the disorders and by the diverse and
      interactive exposures both at, and away from, the workplace. Current studies
      suggest that forceful, repetitive manual work, along with prolonged static
      loading and exposure to vibration are established areas of risk. Much less is
      known about the possible contribution of psychological factors. Perception of
      work characteristics, for example, low decision latitude and lack of social
      support, appear to show increased associations with a number of upper limb
      disorders, although mechanisms to explain these observations are still broadly
      theoretical. Research into individual factors is limited, but age and gender both
      appear to be important.

PMID- 9263928
TI  - Impairment in the medical and legal professions.
AB  - Male doctors and lawyers are among the job groups with high mortality from
      alcohol-related diseases, although the prevalence of substance misuse among these
      groups is not known. Both professions have occupational risk factors. This
      article describes aspects of the work environment which have facilitated
      substance misuse by doctors and lawyers, and describes the professional
      consequences of addiction. Data will be presented from two studies: a
      retrospective casenote survey of doctors treated for substance misuse; and a
      questionnaire survey of lawyers in recovery from alcohol problems. Mechanisms for
      assisting impaired professionals into treatment have been developed in the UK and
      the USA. The most successful models separate health procedures from disciplinary
      procedures as much as possible, and offer a confidential evaluation and treatment
      program. Self-help groups play a crucial role in these therapeutic processes.

PMID- 9263929
TI  - Technological stress: psychophysiological symptoms in modern offices.
AB  - Increasingly, employees in modern office environments report suffering from
      psychosomatic symptoms. Studies of employees in high-technology industries
      suggest that psychosomatic symptoms are related in part to high perceived mental
      demands in combination with lack of sufficient skills. Employees with symptoms
      more commonly report that they are not sufficiently recognized by their employer,
      as compared with nonsymptomatic peers. Low perceived organizational efficiency
      correlates with high mental stress among employees. In a controlled stress
      management program, we observed lower mental stress levels among participants, as
      compared with controls, and lower physiological arousal, measured as circulating
      levels of prolactin. It is suggested that organizational reengineering and the
      introduction of information technologies constitute potential stressors
      challenging employees' cognitive resources. It is predicted that psychosomatic
      syndromes in the workplace will most likely increase in the foreseeable future
      due to the rapid changes currently transcending working life.

PMID- 9263930
TI  - Non-specific symptoms in response to hazard exposure in the workplace.
AB  - Recent concerns in occupational health have shown a shift in emphasis from the
      study of diseases with well-established pathology toward the investigation of
      conditions characterized by a range of nonspecific symptoms. Exposure to
      potential hazards differing widely in terms of their physical nature or chemical
      composition, for example, electromagnetic fields, organophosphate-based
      pesticides, and organic solvents, frequently results in the reporting of a
      relatively consistent group of symptoms. Furthermore, these symptoms may arise
      among groups of workers where no specific physical or chemical cause can be
      implicated; for example, in many cases of sick building syndrome. The role of
      psychosocial factors in the expression of ill-health has been well-documented in
      the psychological literature. Important modifying factors include the attitudes
      and belief systems of the individuals concerned, certain personality and behavior
      patterns, and the presence of current stress or pre-existing psychological
      distress. In addition, social processes may be involved in the generation and
      reinforcement of health concerns at the group level. These include the workers'
      perceptions of the competence and credibility of managers and professionals, and
      the influence and involvement of the media, pressure groups, and the legal
      system. A proper understanding of the association between putative hazards and
      the reporting of nonspecific symptoms therefore requires consideration not only
      of the direct physical pathway between hazard and harm, but also an assessment of
      factors which may modify the relationship between exposure and symptom reporting.
      The results of such investigations have important implications for determining
      the focus of any management and control strategies which may subsequently be
      implemented in the workplace.

PMID- 9263931
TI  - Perceived sources of work stress and satisfaction among hospital and community
      mental health staff, and their relation to mental health, burnout and job
      satisfaction.
AB  - This questionnaire study examined perceived sources of stress and satisfaction at
      work among 121 mental health staff members. Five factors were derived from
      principal component analysis of sources of work stress items (stress from: role,
      poor support, clients, future, and overload), and accounted for 70% of the total
      variance. Four factors were derived from the items related to sources of job
      satisfaction (satisfaction from: career, working with people, management, and
      money), accounting for 68% of the variance. The associations of these factors
      with sociodemographic and job characteristics were examined, and they were
      entered as explanatory variables into regression models predicting mental health,
      burnout, and job satisfaction. Stress from "overload" was associated with being
      based outside an in-patient ward, and with emotional exhaustion and worse mental
      health. Stress related to the "future" was associated with not being white.
      Stress from "clients" was associated with the "depersonalization" component of
      burnout. Higher job satisfaction was associated with "management" and "working
      with people" as sources of satisfaction, whereas emotional exhaustion and poorer
      mental health were associated with less "career" satisfaction.

PMID- 9263932
TI  - Improving stress assessment: toward an evidence-based approach to organizational
      stress interventions.
AB  - There is little evidence to suggest that the stress management interventions
      (SMIs) used in organizations are necessarily effective nor is it clear why, in
      principle, they should be. Why then do organizations introduce SMIs? A wide
      variety of reasons is apparent, many focusing on reducing the presumed costs of
      stress and the attractiveness of what appears to be a panacea-like intervention.
      The central aim of this study is to make the case for and outline an evidence
      based approach to SMIs in which data gathered from initial assessments are used
      to make decisions about interventions. Valid assessment requires a relatively
      sophisticated and comprehensive approach to measurement; designs which permit
      causal relationships between the phenomena of interest to be established; and a
      healthy scepticism toward the claims that are made by organizations and
      individuals about stress. It is argued that an evidence-based approach will lead
      to advances in theory development and intervention practices.

PMID- 9263933
TI  - Work and psychiatric disorder in the Whitehall II Study.
AB  - It is important that the effects of work on mental health are investigated when
      work practices are changing rapidly and there is decreasing job security. This
      has been examined in the Whitehall II Study, a cohort study of 6895 male and 3413
      female, London-based civil servants, aged 35-55 years at baseline in 1985. Work
      characteristics were measured by modified Karasek indices in a self-report
      questionnaire. Psychiatric disorder was measured by the 30-item General Health
      Questionnaire (GHQ). In longitudinal analyses in men and women, high work social
      support predicted lower GHQ scores, and high job demands predicted higher GHQ
      scores at follow-up. High work social support and high skill discretion were
      protective against taking short spells of psychiatric sickness absence. The
      protective effects of social support at work and the potential risk of job
      demands have implications for management, job design, training, and further
      research.

PMID- 9263934
TI  - Fatigue in the workforce of National Health Service Trusts: levels of
      symptomatology and links with minor psychiatric disorder, demographic,
      occupational and work role factors.
AB  - The aims of this study were: (1) to obtain a systematic estimate of the levels of
      fatigue in representative samples of the major occupational groups of health care
      workers; (2) to examine the relationship between fatigue and mental health as a
      function of occupational and work role factors; and (3) to test the proposition
      that fatigue arises from a combination of poor mental health and high job stress.
      Questionnaire data from 7720 NHS Trust staff was used. Higher levels of fatigue
      were reported among health care workers in comparison with general population
      figures. Highest levels of general fatigue, the subjective sensation of
      tiredness, were experienced by doctors (especially women doctors), professions
      allied to medicine and managers. Highest levels of fatigability, the onset of
      symptoms after exertion, were experienced by ancillary and nursing staff. Both
      general fatigue and fatigability were associated with high levels of
      psychological distress. Support was also found for the proposition that fatigue
      arises from a combination of poor mental health and high work demands.

PMID- 9263935
TI  - Psychological well-being at work: is prevention better than cure?
AB  - This article describes a comparative stress management intervention study. The
      impacts and outcomes of an individual level intervention (counseling) and an
      organizational level intervention (increasing employees' participation and
      control) are compared. The results suggest that counseling has clear benefits for
      employees' psychological well-being and that the organizational intervention does
      not. Neither intervention had any impact on perceptions of work characteristics,
      physical symptoms, or absenteeism. It is suggested that the causal relationship
      between the work environment and psychological distress have not been
      demonstrated and that techniques for bringing about change in complex
      organizations are poorly developed. For these reasons, the strategy of changing
      work conditions cannot, at present, be expected to improve the psychological
      states of employees. Thus, whereas organizational interventions that aim to
      prevent psychological distress may be "better" in ethical and moral terms,
      individual interventions that aim to treat existing psychological problems or
      help individual employees manage difficult working conditions appear to be
      "better" in terms of efficacy and efficiency.

PMID- 9263936
TI  - Insurance issues: beyond the small print.

PMID- 9263937
TI  - A study of suicide in farmers in England and Wales.
AB  - The proportional mortality ratio for suicide is higher in farmers than in the
      general population. The reasons for this are likely to be complex, but may
      include easy availability of firearms, stress related to work, financial
      difficulties, and family problems. A psychological autopsy study of suicide in 84
      farmers who died between 1991-1994 is presented and some preliminary findings are
      discussed.

PMID- 9263938
TI  - The percentage of consonants correct (PCC) metric: extensions and reliability
      data.
AB  - Research in normal and disordered phonology requires measures of speech
      production that are biolinguistically appropriate and psychometrically robust.
      Their conceptual and numeric properties must be well characterized, particularly
      because speech measures are increasingly appearing in large-scale epidemiologic,
      genetic, and other descriptive-explanatory database studies. This work provides a
      rationale for extensions to an articulation competence metric titled the
      Percentage of Consonants Correct [PCC; Shriberg & Kwiatkowski, 1982; Shriberg,
      Kwiatkowski, Best, Hengst, & Terselic-Weber, 1986], which is computed from a 5-
      to 10-minute conversational speech sample. Reliability and standard error of
      measurement estimates are provided for 9 of a set of 10 speech metric including
      the PCC. Discussion includes rationale for selecting one or more of the 10
      metrics for specific clinical and research needs.

PMID- 9263939
TI  - The speech disorders classification system (SDCS): extensions and lifespan
      reference data.
AB  - A companion paper includes rationale for the use of 10 metrics of articulation
      competence in conversational speech (Shriberg, Austin Lewis, McSweeny, & Wilson,
      1997). The present paper reports lifespan reference data for these measures using
      records from a total of 836 3- to 40(+)-year-old speakers with normal and
      disordered speech. The reference data are subdivided by diagnostic classification
      based on extensions to an instrument titled the Speech Disorders Classification
      System (SDCS; Shriberg, 1993). Appendices provide procedural information on the
      SDCS and statistical rationale for the reference data.

PMID- 9263940
TI  - Three accounts of the grammatical morpheme difficulties of English-speaking
      children with specific language impairment.
AB  - Several hypotheses have been offered to explain the grammatical morpheme
      difficulties observed in the speech of children with specific language
      impairment. Three of the accounts that could be evaluated in English were the
      focus of this study: the extended optional infinitive account, the implicit rule
      deficit account, and the surface account. Preschoolers with specific language
      impairment, a group of age controls, and a group of younger children matched for
      mean length of utterance were evaluated in their use of several theory-relevant
      grammatical morphemes. The findings revealed advantages for both the surface and
      extended optional infinitive hypotheses. In contrast, a test of the predictions
      based on the implicit rule deficit account suggested that the children studied
      here were not experiencing a deficit of this type.

PMID- 9263941
TI  - Response latency and verbal complexity: stochastic models of individual
      differences in children with specific language impairments.
AB  - Within-subject statistical modeling techniques were employed to investigate
      individual differences in the extent to which two possible indicators of
      processing time predicted changes in utterance complexity during spontaneous
      discourse for 10 children ages 7;1 to 10;1 with specific language impairments
      (SLI) who differed in receptive language abilities. The two indicators of
      processing time that were modeled were response latency and the use of a specific
      discourse marker (Verbal Pause) that provided children with additional time to
      respond. Longer response latencies were not a strong predictor of increased
      utterance length for any of the children. However, results indicated that
      children with better receptive skills used substantially more verbal pauses than
      children with both expressive and receptive deficits and that the use of these
      pauses was a strong predictor of increased utterance length for children with
      better comprehension skills.

PMID- 9263942
TI  - The extent to which psychometric tests differentiate subgroups of children with
      SLI.
AB  - This paper reports on the results of a large project involving 7-year-old
      children attending language units in England. A group of 242 children with
      specific language impairment (SLI) were assessed on a battery of psychometric
      tests. In addition, teacher interviews were carried out to ascertain teachers'
      opinions of the children's difficulties. Cluster analysis revealed six robust
      subgroups of children with language difficulties. The findings are discussed in
      the context of other approaches to the classification of language impairment in
      children with special reference to the work of Rapin and Allen (1987).

PMID- 9263943
TI  - Epidemiological and offspring analyses of developmental speech disorders using
      data from the Colorado Adoption Project.
AB  - Although the adoption design is the most powerful method to disentangle nature
      and nurture, it has not been applied previously to developmental speech or
      language disorders. The present study examined the speech outcomes of 156 adopted
      and nonadopted children at varying risk for speech disorders based upon self
      reported parental speech history. The sample consisted of four groups: (a) 16
      adopted children with an affected biological parent; (b) 19 adopted children with
      an affected adoptive parent; (c) 31 nonadopted children with an affected natural
      parent; and (d) 90 low-risk adopted and nonadopted children with no parental
      speech disorder history. Results revealed that 25% of the children with a genetic
      background of speech disorder displayed questionable speech, language, or fluency
      skills at age 7, in comparison to 9% of the children with no known genetic
      history. Logistic regression analyses indicated that positive biological parental
      background was the best predictor of offspring affected status. The child's Full
      Scale IQ and the HOME Scale of family environment were not significantly
      associated with speech outcome. These results provide additional evidence that
      genetic factors contribute importantly to the vertical transmission of some
      developmental speech disorders of unknown origin.

PMID- 9263944
TI  - Auditory processing in individuals with mild aphasia: a study of resource
      allocation.
AB  - This study examined the effects of lesion location (frontal vs. posterior) and
      nature of distraction (nonverbal vs. verbal secondary, competing task) on mildly
      aphasic individuals' performances of listening tasks that required semantic
      judgments and lexical decisions under isolation, focused attention, and divided
      attention conditions. Despite comparable accuracy among all groups during
      isolation conditions, the aphasic groups responded less accurately and more
      slowly than the normal control group during focused and divided attention
      conditions. Generally, the two aphasic groups performed similarly, quantitatively
      and qualitatively. Demographic characteristics such as time post stroke did not
      correlate with performance decrements. Independent of group, all individuals
      showed greater disruption of auditory processing skills when the secondary task
      was verbal rather than nonverbal. Within a limited-capacity model of attention,
      the results suggest that aphasic individuals display impairments of attention and
      resource allocation and that these impairments negatively interact with their
      auditory processing abilities.

PMID- 9263945
TI  - Grammatical deficits in Italian-speaking children with specific language
      impairment.
AB  - In earlier work, Italian-speaking children with specific language impairment
      (SLI) have been shown to exhibit a profile of grammatical morpheme difficulties
      that is quite different from the profile seen for English-speaking children with
      SLI. In the present study, this difference was confirmed using a wider range of
      grammatical morpheme types. A group of Italian-speaking children with SLI
      produced articles and third person plural verb inflections with lower percentages
      in obligatory contexts than a group of age controls and a group of younger
      controls matched for mean length of utterance (MLU). However, the children with
      SLI closely resembled the MLU controls in their production of noun plural
      inflections, third person copula forms, first person singular and plural verb
      inflections, and third person singular verb inflections. Errors on articles and
      copula forms were usually omissions whereas errors on verb inflections were
      usually productions of inappropriate finite inflections. Infinitives were seen in
      contexts requiring finite forms but they were not the dominant error type. Data
      from comprehension tasks raise the possibility that production factors were
      responsible for some of the differences seen. The findings of this study suggest
      that accounts of SLI are incomplete unless they assign a major role to the
      relative case of identifying and interpreting the relevant data in the ambient
      language. The implications of these findings for current accounts of SLI are
      discussed.

PMID- 9263946
TI  - Adults recovered from stuttering without formal treatment: perceptual assessment
      of speech normalcy.
AB  - The purpose of this study was to determine if the speech of adults who self
      judged that they were recovered from stuttering without the assistance of
      treatment is perceptually different from that of adults who never stuttered.
      Fifteen adult speakers verified as persons who had recovered from a valid
      stuttering problem without the assistance of treatment were compared with 15
      adult speakers verified as persons with normally fluent speech. Judges viewed
      videotaped speech samples of all speakers and were instructed to decide whether a
      speaker used to stutter or never stuttered. A separate group of judges rated the
      same samples for speech naturalness. Various speech behavior measures were also
      obtained. Results revealed that the speech of speakers who used to stutter was
      perceptually different from that of speakers who never stuttered. This difference
      was correlated with unnatural sounding speech and a high frequency of part-word
      repetitions.

PMID- 9263947
TI  - Modifications in aerodynamic variables by persons who stutter under fluency
      evoking conditions.
AB  - The purposes of this study were to (a) compare the effects of fluency-evoking
      conditions on aerodynamic variables in 10 persons who stutter with those
      previously reported for 12 individuals who do not stutter; (b) determine if any
      changes demonstrated in the amplitude and/or timing of aerodynamic variables were
      accounted for by changes in speech intensity; and (c) determine if any amplitude
      or timing changes in flow and intraoral pressure were related to improved
      fluency. The fluency-evoking conditions were choral reading (CR), metronome
      pacing (MET), delayed auditory feedback (DAF), and noise (NOISE). From 8 words
      beginning with plosive consonants in CVC contexts read aloud in sentences,
      measures were made of 8 variables, including closure duration, amplitude and time
      to maximum airflow and intraoral pressure for initial plosives, and the duration
      and intensity of the following vowel. Speech rate was also computed. Only
      fluently produced target words from persons who stutter were analyzed. All
      persons who stutter showed improved fluency under all conditions. Both groups
      demonstrated significant (p < or = 0.006) condition effects for peak flow, vowel
      intensity, and pressure rise time. Thus, fluency-evoking conditions affected
      these variables regardless of speaker type. Both groups changed peak pressure in
      similar directions from baseline depending on condition, but not significantly
      for each group in the same conditions. Persons who stutter significantly
      increased speech rate for CR, DAF, and NOISE; and persons who do not stutter
      significantly decreased rate under DAF. The reported changes in peak pressure and
      peak flow could not be accounted for by changes in vowel intensity. Larger
      improvements in fluency occurred under conditions when peak flow and peak
      pressure values were decreased from baseline. Thus, variables that were modified
      by both groups when speaking under conditions were also the variables related to
      changes in fluency for the persons who stutter.

PMID- 9263948
TI  - The response to sudden change in vocal tract resistance during stop consonant
      production.
AB  - The speech respiratory system is configured in ways that tend to maximize its
      ability to respond to changes in the airway environment. Intraoral pressures
      remain at levels sufficient to generate reliably recognized consonant sounds even
      in the presence of structural deficits such as velopharyngeal inadequacy. Similar
      respiratory compensations occur when bite blocks and bleed valves are used to
      vent airway pressures. The purpose of the present study was to determine the
      sensitivity of the monitoring system psychophysically and to assess its
      physiological response to sudden, unanticipated perturbations. Twenty adults were
      asked to produce the utterance/pa/, and a calibrated perturbator valve permitted
      air to escape from the oral cavity on randomly selected productions. Respiratory
      responses were recorded using PERCI-SARS instrumentation. The results indicated
      that sudden openings of 0.14 cm2 (SD = 0.04) were detected by speakers.
      Compensatory respiratory responses to suprathreshold pressure-venting occurred
      rapidly (i.e., 27 ms [SD = 8]) after valve opening. Although peak pressure and
      area under the pressure pulse fell with valve opening, the magnitude of pressure
      was nevertheless sufficient for sound generation. Measurements of the slope of
      the rise in intraoral pressure after subthreshold pressure-venting in 10
      participants were compared to measurements obtained from an-elastic model of the
      upper airway. The data demonstrated a significant difference between vented and
      unvented conditions for the model, but not the participants. This suggests that
      elastic recoil is actively and unconsciously controlled in humans to compensate
      for losses in airway pressure during speech.

PMID- 9263949
TI  - Interspeaker variation in habitual speaking rate: evidence for a neuromuscular
      component.
AB  - Neuromuscular and sociolinguistic hypotheses were proposed to explore and account
      for the nature of individuals' idiosyncratic speech rates. One hundred subjects
      (50 males and 50 females) read the Farm Script passage at both habitual and
      maximum rates. FAST and SLOW subgroups of subjects were selected for both genders
      based on their overall speaking rates. The articulation rate data derived from 30
      selected subjects (SLOW and FAST) revealed the following findings: (a) a
      significant linear regression function existed between the habitual and maximum
      rates, (b) significantly different maximum rates were found for the SLOW and the
      FAST groups, (c) roughly equivalent relative changes from habitual to maximum
      rate for both SLOW and FAST groups. No significant gender differences were found
      across different speech tasks and measures of speech rates. The weight of the
      evidence seems to suggest that neuromuscular constraints play a role in the
      determination of an individual's habitual speaking rate. Nevertheless, the study
      did not suggest that either neuromuscular hypotheses or sociolinguistic
      hypotheses alone can account for the control of individuals' speaking rates due
      to the unusual ability demonstrated by a few subjects in the SLOW group, to speak
      at very fast maximum rates.

PMID- 9263950
TI  - Children recovered from stuttering without formal treatment: perceptual
      assessment of speech normalcy.
AB  - Current evidence suggests that young children who recover from stuttering are
      essentially stutter-free. However, there is no evidence to indicate if their
      speech is perceptually indistinguishable from normally fluent peers or whether
      they retain perceptually unusual speech. One important example of recovery from
      stuttering is children who have recovered without receiving formal treatment. An
      investigation was conducted to determine if the speech of these children is
      perceptually different from the speech of children who have never stuttered.
      Speakers consisted of 10 preschool and early school-age children documented as
      recovered from stuttering without benefit of formal treatment. In a series of
      studies they were compared with 10 children who had never stuttered. Three groups
      of judges-sophisticated, unsophisticated, and experienced-were separately asked,
      using videotaped speech samples of the children, to decide which samples were
      from children who used to stutter. Results revealed that the children who
      recovered from stuttering were perceptually indistinguishable from the normal
      controls. The same result was obtained regardless of whether the samples were
      presented in paired-stimulus or single-stimulus mode. Two of the groups of judges
      were also instructed to rate the speech naturalness of the speech samples. The
      speakers were not distinguished on this measure either. Methodological issues and
      the implications of the findings are discussed.

PMID- 9263951
TI  - Lip and jaw kinematics in bilabial stop consonant production.
AB  - This paper reports two experiments, each designed to clarify different aspects of
      bilabial stop consonant production. The first one examined events during the
      labial closure using kinematic recordings in combination with records of oral air
      pressure and force of labial contact. The results of this experiment suggested
      that the lips were moving at a high velocity when the oral closure occurred. They
      also indicated mechanical interactions between the lips during the closure,
      including tissue compression and the lower lip moving the upper lip upward. The
      second experiment studied patterns of upper and lower lip interactions, movement
      variability within and across speakers, and the effects on lip and jaw kinematics
      of stop consonant voicing and vowel context. Again, the results showed that the
      lips were moving at a high velocity at the onset of the oral closure. No
      consistent influences of stop consonant voicing were observed on lip and jaw
      kinematics in five subjects, nor on a derived measure of lip aperture. The
      overall results are compatible with the hypothesis that one target for the lips
      in bilabial stop production is a region of negative lip aperture. A negative lip
      aperture implies that to reach their virtual target, the lips would have to move
      beyond each other. Such a control strategy would ensure that the lips will form
      an air light seal irrespective of any contextual variability in the onset
      positions of their closing movements.

PMID- 9263952
TI  - Miniature head-mounted microphone for voice perturbation analysis.
AB  - The miniature head-mounted microphone has become the microphone of choice in
      clinics, laboratories, and professional work settings where voice amplification
      or recording is needed and subject mobility is desirable. In this study, a
      miniature head-mounted condenser microphone was compared to a larger,
      professional grade stand-mounted condenser microphone for perturbation analysis.
      Amplitude and frequency perturbation measures of human phonation were made for
      comparison. The results indicate that only small differences exist between the
      two microphones. The only exception is when there is significant head movement,
      in which case the head-mounted microphone offers an advantage. Errors associated
      with variable source-to-microphone distance can therefore be reduced without
      losing baseline quality in transducing voice signals for analysis.

PMID- 9263953
TI  - Relationships between subjective ratings and objective measures of performance in
      speechreading sentences.
AB  - Ninety-six participants with normal hearing and 63 with severe-to-profound
      hearing impairment viewed 100 CID Sentences (Davis & Silverman, 1970) and 100 B-E
      Sentences (Bernstein & Eberhardt, 1986b). Objective measures included words
      correct, phonemes correct, and visual-phonetic distance between the stimulus and
      response. Subjective ratings were made on a 7-point confidence scale. Magnitude
      of validity coefficients ranged from .34 to .76 across materials, measures, and
      groups. Participants with hearing impairment had higher levels of objective
      performance, higher subjective ratings, and higher validity coefficients,
      although there were large individual differences. Regression analyses revealed
      that subjective ratings are predictable from stimulus length, response length,
      and objective performance. The ability of speechreaders to make valid performance
      evaluations was interpreted in terms of contemporary word recognition models.

PMID- 9263954
TI  - Effect of time and frequency manipulation on syllable perception in developmental
      dyslexics.
AB  - Many people with developmental dyslexia have difficulty perceiving stop consonant
      contrasts as effectively as other people and it has been suggested that this may
      be due to perceptual limitations of a temporal nature. Accordingly, we predicted
      that perception of such stimuli by listeners with dyslexia might be improved by
      stretching them in time-equivalent to speaking slowly. Conversely, their
      perception of the same stimuli ought to be made even worse by compressing them in
      time-equivalent to speaking quickly. We tested 15 children with dyslexia on their
      ability to identify correctly consonant-vowel-consonant (CVC) stimuli that had
      been stretched or compressed in the time domain. We also tested their perception
      of the same CVC stimuli after the formant transitions had been stretched or
      compressed in the frequency domain. Contrary to our predictions, we failed to
      find any systematic improvement in their performance with either manipulation. We
      conclude that simple manipulations in the time and frequency domains are unlikely
      to benefit the ability of people with dyslexia to discriminate between CVCs
      containing stop consonants.

PMID- 9263955
TI  - Effect of acoustic cues on labeling fricatives and affricates.
AB  - Previous studies have shown that manipulation of frication amplitude relative to
      vowel amplitude in the third formant frequency region affects labeling of place
      of articulation for the fricative contrast /s/-/integral of/ [Hedrick & Ohde,
      1993; Stevens, 1985]. The current study examined the influence of this relative
      amplitude manipulation in conjunction with presentation level, frication
      duration, and formant transition cues for labeling fricative place of
      articulation by listeners with normal hearing and listeners with sensorineural
      hearing loss. Synthetic consonant-vowel (CV) stimuli were used in which the
      amplitude of the frication relative to vowel onset amplitude in the third formant
      frequency region was manipulated across a 20 dB range. The listeners with hearing
      loss appeared to have more difficulty using the formant transition component than
      the relative amplitude component for the labeling task than most listeners with
      normal hearing. A second experiment was performed with the same stimuli in which
      the listeners were given one additional labeling response alternative, the
      affricate /t integral of/. Results from this experiment showed that listeners
      with normal hearing gave more /t integral of/ labels as relative amplitude and
      presentation level increased and frication duration decreased. There was a
      significant difference between the two groups in the number of affricate
      responses, as listeners with hearing loss gave fewer /t integral of/ labels.

PMID- 9263956
TI  - Scalp potentials evoked by amplitude-modulated tones in dyslexia.
AB  - We recorded the far-field EEG potential evoked by amplitude modulation of
      acoustic stimuli (the amplitude modulation following response, AMFR) in adults
      with developmental dyslexia and in a matched control group of adults with no
      history of reading problems. The mean AMFR recorded from participants with
      dyslexia was significantly smaller than that recorded from members of the control
      group. In contrast, the amplitude of the click-evoked auditory brainstem response
      (ABR) was not significantly different between participant groups. Also, there was
      no difference between participant groups in the latency of the AMFR or ABR. The
      reduced AMFR in listeners with dyslexia may reflect impaired ability of the
      auditory system to follow rapid changes in stimulus energy, a cue believed to be
      important in the perception of speech.

PMID- 9263957
TI  - Auditory development in complex tasks of comodulation masking release.
AB  - Experiments on listeners aged 5 years to adult were conducted to investigate the
      development of comodulation masking release (CMR) under conditions where auditory
      grouping could be affected either by the coherence of modulation pattern among
      noise bonds, or the temporal asynchrony among bands. The conditions examining CMR
      when two modulation patterns were present (each carried by a different set of
      noise bands) indicated a similar effect across all age groups. Here, CMR was
      substantial when the on-signal band (OSB) and six comodulated flanking bands
      (FBs) were presented, decreased when two bands having a second pattern of
      modulation were added, and then recovered partially when a further six bands that
      had the second modulation pattern were added. In conditions where there was a
      temporal asynchrony between the OSB and the FBs, the children typically showed
      smaller CMRs than the adults. In the case where the OSB preceded the FBs, adults
      typically showed CMR near zero when the temporal fringe was 50 ms or more.
      Children usually showed negative CMRs for such conditions. In the case where the
      FBs preceded the OSB, all age groups showed substantial CMRs, but the CMRs of
      adults were significantly larger than those of the children. The present results
      indicate that the effect of a second, independent modulation pattern on CMR is
      similar in children and adult listeners, but that CMR appears to be detrimentally
      affected more in children than in adults when there is a temporal asynchrony
      between the on-signal and flanking bands.

PMID- 9263958
TI  - MLD in children: effects of signal and masker bandwidths.
AB  - The first aim of this study was to obtain a more detailed picture of the effect
      of masker bandwidth (20 Hz to 1000 Hz bandwidth) on the masking level difference
      (MLD) for a 500-Hz signal as a function of listener age. The results of the pure
      tone signal experiment showed that the MLDs of older children differed from
      adults only for the narrowest masker bandwidth. In contrast, children younger
      than about 7 years of age tended to have smaller MLDs than adults at all but the
      widest masker bandwidth must be for MLDs of adult magnitude to be observed. One
      interpretation of this effect is that younger listeners require relatively great
      spectral dissimilarity (and, therefore perceptual dissimilarity) between the
      signal and masker in order to obtain MLDs of adult magnitude. The second aim of
      this study was to test this possibility by determining the MLD for noise signals
      in cases where the signal and masker bandwidths were the same. The results of
      this experiment showed that the MLDs of children were as large as those of adults
      when the signal/masker bandwidth was 320 Hz, but were smaller than those of
      adults when the signal/masker bandwidth was 20 Hz. This indicates that the factor
      limiting the MLD for narrowband noise in children is related more to the masker
      bandwidth than to the perceptual similarity between the signal and the masker.

PMID- 9263959
TI  - The future of medicine in Hong Kong, SAR, China.

PMID- 9263960
TI  - Acne.

PMID- 9263961
TI  - The autoimmune bullous diseases.

PMID- 9263962
TI  - Surgery and laser therapy.

PMID- 9263963
TI  - HIV-related skin diseases.

PMID- 9263964
TI  - Molecular genetic approaches to skin disease: keratins and keratinisation.

PMID- 9263965
TI  - Nuclear medicine: guidelines for the provision of a clinical service. Report of a
      Working Group of the Royal College of Physicians Nuclear Medicine Committee.

PMID- 9263966
TI  - Specialist paediatric health services and academic departments--what and where?

PMID- 9263967
TI  - Health/ill-health transition in less privileged populations: what does the future
      hold?
AB  - Changes in health/ill-health in response to alterations in environmental factors
      are recognised. While the phenomenon has been extensively investigated in Western
      populations, the extent and sequelae of transitions in less privileged
      populations are less well appreciated. Examples of changes are given, first for
      Western populations as a comparison but, more particularly, for rural and urban
      Africans, for African-Americans, and also for Australian Aboriginals, whose
      mortality rates for chronic degenerative diseases now exceed those of white
      Australians. Discussion of the likely future of these populations indicates that
      a lessening of proneness to Western diseases is unlikely.

PMID- 9263968
TI  - Age-related variations in presentation and outcome in Wegener's granulomatosis.
AB  - Wegener's granulomatosis (WG) is increasingly being diagnosed in older people.
      The object of this study was to see whether age influences the clinical
      presentation and prognosis. In a retrospective open case-note review of 51
      patients with a diagnosis of WG based on internationally accepted criteria, 29
      patients (56.9%) below 60 years and 22 (43.1%) aged 60 or above were compared.
      The incidence of limited (10% vs 9.1%) and classical (89.6% vs 90.9%) disease was
      similar in the two groups, but some clinical features were commoner in the
      younger cohort at presentation: ear, nose and throat (100% vs 68.1%; p < 0.01),
      ophthalmic (48.3% vs 18.2%; p = 0.05) and dermatological (51.7% vs 18.2%; p =
      0.05). There were no significant differences in the incidence of renal,
      pulmonary, rheumatological or neurological involvement or in the presence of
      antineutrophil cytoplasmic antibody. Outcome was significantly worse for the over
      60 group despite a similar treatment regimen (prednisolone, cyclophosphamide, and
      dialysis if required) (six months' survival: 96.5% vs 59.1%; p < 0.01). Renal
      function at presentation was a significant determinant of prognosis: mean serum
      creatinine at presentation was 525 mumol/l vs 291 mumol/l respectively in those
      who died within six months and in those who survived (p = 0.03). Uncontrolled
      pulmonary vasculitis was the commonest cause of death. In conclusion, the
      classical presentations of WG are similar in older patients. Disease in the
      latter is more often restricted to the lungs and the kidneys, and this may cause
      diagnostic uncertainty. The outcome is worse in older patients, with uncontrolled
      pulmonary vasculitis the commonest cause of death despite immuno-suppressive
      treatment. Early diagnosis and treatment may improve outcome.

PMID- 9263969
TI  - One-stop chest pain clinic can identify high cardiac risk.
AB  - The aim of this study was to record prognosis for patients with stable chest pain
      referred for outpatient cardiac assessment. All 660 patients in the study had a
      normal resting ECG and no history of myocardial infarction, unstable angina or
      coronary revascularisation. Main outcome measures were all-cause mortality, non
      fatal ischaemic events and coronary revascularisation. Cardiac chest pain was
      diagnosed in 182 patients (28%). It was more frequent in patients with recent
      onset of symptoms (< 6 months), patients over 50, white patients, and patients
      with hypertension or diabetes. The mean follow-up was 622 +/- 338 days. Among
      survivors, 37% continued to suffer from symptoms (cardiac group: 59 (35.1%); non
      cardiac group: 177 (38.4%)). When all hard events were considered, event-free
      survival (95% confidence interval) for the cardiac group was 90.9% (86.7-95.2%)
      at six months, 88.9% (84.2-93.6%) at one year, and 83.6% (77.5-89.7%) at two
      years. Corresponding figures for the non-cardiac group at the same time points
      were better (p < 0.0001): 98.5% (97.4-99.6%), 97.5% (96.1-99.0%) and 96.6% (94.7
      98.5%), respectively. In conclusion, the use of clinical criteria in a cardiac
      outpatient clinic, backed up by simple non-invasive investigations, can reliably
      identify a population at high risk of subsequent cardiac events.

PMID- 9263970
TI  - Continuing professional development in public health medicine.
AB  - BACKGROUND: A survey of public health doctors was undertaken in the South Thames
      region to support coordination of continuing professional development (CPD) and
      to guide appropriate provision of educational activities for those working in the
      specialty. METHODS: A postal survey of 130 public health doctors in service,
      academic and military posts in the South Thames region of the UK. RESULTS: The
      response rate was 79% with good representation of grades and geographical areas.
      Public health doctors preferred personal and small group learning particularly
      focused on problem solving. Epidemiology as a basic discipline was rated highly
      by respondents, but senior doctors also showed preferences for topics beyond the
      textbooks. Respondents demonstrated that they had acquired such knowledge and
      skills, which could be shared in CPD sessions with colleagues. There was support
      for learning with and from non-medical colleagues. In the service posts
      structural change was ongoing, expectations of performance by management were
      high, and appropriate CPD was an expressed need, although time was seriously
      limited for this activity. CONCLUSIONS: Appropriate CPD could support the
      effectiveness of public health physicians in challenging circumstances. However,
      a critical evaluation of the relevance of CPD programmes to public health
      practice is essential if CPD is to support doctors in delivering the public
      health agenda in the changing structures within which they work.

PMID- 9263971
TI  - Obtaining medical information from the Internet.
AB  - The Internet is rapidly expanding as an environment for electronic communication
      and resource sharing. The World Wide Web, a relatively new service on the
      Internet, provides access to a wealth of information resources through a simple
      point-and-click interface. Available resources of interest to physicians include
      bibliographical and statistical databases, literature reviews, discussion groups,
      press releases, newsletters, drug information, self-assessment questionnaires,
      multimedia textbooks, patient simulations, clinical decision aids, educational
      software, and much more. Access to the Internet is widely available in
      universities and medical libraries; physicians working at home can gain access
      from a personal computer linked by a modem to a telephone line, by subscribing to
      an Internet service provider.

PMID- 9263972
TI  - Down at heart--the meaning and implications of social inequalities in
      cardiovascular disease.

PMID- 9263973
TI  - Sun, sex and responsibility. The Lumleian Lecture 1996.

PMID- 9263974
TI  - Transplantation: some British pioneers.

PMID- 9263975
TI  - Medical statues.

PMID- 9263976
TI  - Medicine, artists and their art.

PMID- 9263978
TI  - Medicine in Hong Kong (and China) since 1841.

PMID- 9263979
TI  - The treatment of minimal change nephropathy and focal segmental
      glomerulosclerosis.

PMID- 9263977
TI  - Hong Kong's eastern and western medical history.

PMID- 9263980
TI  - The early repetition of deliberate self harm.

PMID- 9263981
TI  - Increasing demand for dermatological services.

PMID- 9263982
TI  - Improving communication between doctors and patients.

PMID- 9263983
TI  - The balance of acid, base and charge in health and disease.

PMID- 9263984
TI  - Cell-cycle control and renal disease.

PMID- 9263985
TI  - Receptor protein tyrosine kinases in perinatal developing rat kidney.
AB  - We have identified receptor protein tyrosine kinases (PTKs) that are expressed
      and/or activated during kidney development. mRNA from fetal rat kidneys in late
      gestation (embryonic day 21), was used to prepare a cDNA template for polymerase
      chain reaction amplification with primers based on conserved regions of PTKs, and
      products were subcloned and sequenced. Among 346 clones, we identified epidermal
      growth factor receptor (EGF-R), Tie-2, platelet-derived growth factor receptor
      (PDGF-R)-alpha, PDGF-R beta, Flk-1, Flt-4, fibroblast growth factor receptor (FGF
      R)-1, FGF-R3, FGF-R4, Met, and RYK/Nbtk-1. PTK expression was studied by
      immunoprecipitation and immunoblotting of kidney membrane proteins with specific
      antibodies. EGF-R, PDGF-R alpha, FGF-R1, FGF-R3, Met, and in some cases Tie-2
      protein expression was greater in fetal kidneys, as compared with kidneys from 12
      week-old adult rats (controls). Flk-1, PDGF-R beta, and FGF-R4 proteins were
      expressed comparably, however, Flt-4 was not detected. As a reflection of
      receptor PTK activity, we assessed endogenous tyrosine phosphorylation, and in
      vitro autophosphorylation. EGF-R and PDGF-R alpha displayed activity in fetal,
      but not adult kidneys. FGF-R3 and Flk-1 were active in some fetal kidneys, and
      the other PTKs were not active. Thus, in late gestational rat kidney, there are
      distinct patterns of receptor PTK expression and activity. EGF-R, PDGF-R alpha,
      FGF-R3 and Flk-1 are among the PTKs that are activated, and they may mediate
      perinatal development of renal epithelial, interstitial, or vascular structures.

PMID- 9263986
TI  - Induction of mesangial interleukin-6 synthesis by apoptotic U937 cells and
      monocytes.
AB  - Infiltration of the glomerular mesangium by monocytes and macrophages is a
      central pathologic feature in various forms of glomerulonephritis. Dependent on
      the presence and activity of local survival factors, monocytes may undergo
      apoptosis. Therefore, we looked for the interaction between cultured human
      mesangial cells (HMC) and intact, necrotic or apoptotic monocytic cells with
      different stages of programmed cell death (U937 cells and blood-derived human
      monocytes) and the possible evoked secretory responses of HMC. Interleukin-6 (IL
      6) synthesis of HMC after a two hour co-culture with late apoptotic U937 cells
      was significantly increased (505 +/- 55 pg/ml) as compared to intact U937 cells
      (349 +/- 27 pg/ml; HMC alone, 319 +/- 62 pg/ml), and was further elevated after
      20 hours (815 +/- 108 pg/ml). U937 cells alone, after incubation in HMC
      conditioned medium or after coincubation with HMC, did not produce any detectable
      IL-6. A high mesangial IL-6 synthesis in response to apoptotic U937 cells was
      dependent on the cellular contact between HMC and U937 and could not be mimicked
      by apoptotic U937 culture supernatants. Radiolabeling studies indicated that HMC
      bound (16.6 +/- 2.4%) and ingested (12.5 +/- 1.9%) apoptotic U937 cells to a much
      higher amount as compared to intact U937 (5.3 +/- 2.0% binding; 5.0 +/- 1.1%
      phagocytosis). Binding and ingestion of monocytic cells undergoing apoptosis was
      confirmed by morphologic studies using electron microscopy. Incubation of HMC
      with a blocker of the CD36/ vitronectin receptor (VnR) dependent recognition
      mechanism of phagocytes for apoptotic leukocytes (RGDS peptide) did not alter
      binding, phagocytosis or IL-6 synthesis of HMC in response to apoptotic U937.
      Phospho-L-serine as an antagonist of the phosphatidylserine (PS) mediated
      recognition pathway for apoptotic cell disposal was able to reduce binding and IL
      6 production by HMC but not phagocytosis. Thus, binding of apoptotic monocytic
      cells by HMC rather than ingestion may be the prerequisite for a stimulated
      secretory response. To elucidate whether binding and phagocytosis of particles in
      general might stimulate HMC to produce IL-6, we looked for mesangial IL-6
      production after binding and ingestion of opsonized zymosan particles. In this
      case, IL-6 synthesis was markedly down-regulated. Furthermore, HMC proliferated
      after zymosan treatment, whereas after apoptotic cell uptake the mesangial cell
      number remained constant. In conclusion, apoptotic monocytic cells provoked an
      enhanced mesangial IL-6 synthesis by a PS-dependent recognition mechanism. This
      secretory response may have secondary implications for humoral or cellular
      processes within the mesangium.

PMID- 9263987
TI  - Feedback regulation of extracellular ATP-stimulated phosphoinositide hydrolysis
      by protein kinase C-alpha in bovine glomerular endothelial cells.
AB  - In glomerular endothelial cells, extracellular ATP stimulates a phospholipase C
      with subsequent hydrolysis of polyphosphoinositides and an increase in cytosolic
      free Ca2+ concentration ([Ca2+]i). Short-term (30 min) pretreatment of
      endothelial cells with 12-O-tetradecanoylphorbol 13-acetate (TPA), a potent
      activator of protein kinase C (PKC), decreases the ATP-stimulated
      phosphoinositide degradation and Ca2+ mobilization. However, this inhibition was
      lost after incubating the cells for four hours with TPA. Longer-term pretreatment
      (10 to 48 hr) even potentiated ATP-induced phosphoinositide breakdown and Ca2+
      mobilization. In addition, pretreating the cells for 30 minutes with the specific
      PKC inhibitor Ro 31-8220 dose-dependently increased ATP-stimulated
      phosphoinositide hydrolysis, thus clearly indicating a regulatory role for PKC in
      the inositol lipid signaling pathway in glomerular endothelial cells. By using
      specific antibodies recognizing the different PKC isoenzymes, it is observed that
      glomerular endothelial cells express five isoenzymes: PKC-alpha, -delta, 
      epsilon, -zeta and -theta. No PKC-beta, -gamma, -eta and -mu isoenzymes were
      detected. On exposure to TPA, a complete depletion of PKC-alpha is observed
      within four hours. In contrast, PKC-epsilon was more resistant to phorbol ester,
      and even after 48 hours of TPA treatment, only 60% of PKC-epsilon was down
      regulated. PKC-theta decreased very slowly from the cytosol (47% left after 24 hr
      of phorbol ester treatment) and translocated to the Triton X100-insoluble
      fraction. Moreover, PKC-delta and PKC-zeta were not significantly affected by 48
      hours of phorbol ester incubation. Thus, only PKC-alpha is depleted with a
      kinetic that corresponds to the loss of feedback inhibition of ATP-stimulated
      phosphoinositide turnover. In the next step, [Ca2+]i changes were measured in
      single cells loaded with Fura-2 after microinjection of neutralizing PKC
      isoenzyme-specific antibodies. Injection of antibodies specific for PKC-alpha
      potently increased Ca2+ mobilization in response to ATP stimulation when compared
      to cells injected with buffer only or antibodies specific for PKC-epsilon. These
      results provide evidence that PKC-alpha mediates feedback inhibition of ATP
      stimulated phosphoinositide hydrolysis in glomerular endothelial cells.

PMID- 9263989
TI  - A novel in vivo mechanism for angiotensin type 1 receptor regulation.
AB  - This study examined whether a regulatory mechanism exists for the angiotensin II
      receptor that is compatible with in vivo homeostatic need. Experiments were
      conducted under two different experimental stresses, (1) deletion of receptor
      protein and (2) chronic extracellular fluid (ECF) volume depletion. To circumvent
      potentially dampening intermediary feedback signals in vivo, any feedback gain
      was completely averted through genetic engineering. The coding exon of
      angiotensin type 1A (AT1A) receptor gene (Agtr1a) was targeting-replaced with a
      reporter gene, lacZ, so that the transcription of lacZ, instead of Agtr1a, is
      driven by the native Agtr1a promoter. ECF volume depletion by dietary sodium
      restriction enhanced Agtr1a gene expression in the adrenal gland of wild-type
      mice. However, although blood pressure fell in the homozygous targeted mice,
      Agtr1a gene expression remained unchanged in the adrenal, indicating that adrenal
      Agtr1a gene expression is regulated entirely through angiotensin receptor-ligand
      interactions. In the kidney, AT1A mRNA assessed by Northern blotting also did not
      change in AT1A null-mutated mice with or without sodium restriction. However,
      tissue examinations for lacZ mRNA and activities indicated that sodium
      restriction and receptor protein depletion result in dramatic up-regulation of
      Agtr1a gene expression within the renal arterioles, which can be nullified by an
      experimental normalization of blood pressure. No such change was observed in wild
      type mice. This study demonstrates a presence within the resistance vessel of a
      blood pressure-sensitive mechanism for AT1 receptor regulation that opposes a
      down-regulatory influence of the ligand during ECF volume depletion.

PMID- 9263988
TI  - Evidence against a major role of adenosine in oxygen-dependent regulation of
      erythropoietin in rats.
AB  - This in vivo study investigated whether adenosine (ADO) plays a role in oxygen
      dependent production of erythropoietin (EPO). Exposure of rats to 0.075% carbon
      monoxide (CO) for four hours was used as a stimulus for EPO production. To
      inhibit potential effects of ADO, rats were treated with the non-specific ADO
      antagonist theophylline, the selective ADO A1 receptor blockers DPCPX and KW
      3902, the selective ADO A2 receptor blocker DMPX, and AOPCP, an inhibitor of 5'
      ectonucleotidase, an ADO generating enzyme that is expressed on the surface of
      EPO producing cells. To stimulate ADO receptor activity, animals were treated
      with the selective ADO A1 and A2 receptor agonists CHA and CGS 21680, the ADO
      reuptake inhibitors dipyridamole and soluflazine and the ADO desaminase inhibitor
      EHNA. At doses known to interfere with ADO signal transmission in vivo, none of
      these substances either influenced EPO serum levels in normoxic rats or affected
      the approximately 30-fold rise in EPO serum levels and the increase in renal EPO
      mRNA after exposure to carbon monoxide. Continuous administration of theophylline
      to normoxic rats for seven days did not alter hematocrit, hemoglobin or EPO serum
      levels. Taken together, these experiments do not support the hypothesis that ADO
      plays an important role in the regulation of EPO production.

PMID- 9263990
TI  - Inhibition of platelet-derived growth factor receptor tyrosine kinase by atrial
      natriuretic peptide.
AB  - Atrial natriuretic peptide (ANP) is known to suppress platelet-derived growth
      factor (PDGF)-stimulated proliferation of rat cultured vascular smooth muscle
      cells. The present study examined whether ANP inhibits the PDGF receptor (PDGFR)
      tyrosine kinase activation, an initial event for PDGF cellular signaling. ANP
      reduced the in vivo tyrosine phosphorylation of PDGFR stimulated by PDGF in a
      dose-dependent manner. This effect was not due to the reduction in PDGFR protein
      as detected by immunoblot analysis. 8-Bromo-cyclic GMP, a membrane-permeable
      3',5'-cyclic monophosphate (cGMP) derivative, mimicked the action of ANP. HS-142
      1, an antagonist for guanylate cyclase A (GC-A) and B, co-incubated with ANP,
      restored the PDGF-induced PDGFR autophosphorylation. The effect of ANP was also
      observed in the presence of a protein tyrosine phosphatase inhibitor, sodium
      orthovanadate. To confirm that ANP exerts its action by inhibiting protein
      tyrosine kinase (PTK), an in vitro kinase assay was performed. Cyclic GMP
      inhibited PTK activity of PDGFR partially purified by lectin affinity
      chromatography. In contrast, PTK activity in immobilized PDGFR immunocomplexes
      was not inhibited by cGMP. However, exogenous cGMP dependent protein kinase (PKG)
      reduced the PTK activity in the presence of cGMP. These results demonstrate that
      ANP suppresses PDGFR PTK through GC-A probably by activating PKG. This may be an
      important mechanism by which ANP exerts its anti-proliferative action
      antagonizing PDGF.

PMID- 9263991
TI  - The IGF-I axis in kidney and skeletal muscle of potassium deficient rats.
AB  - Potassium deficiency in the rat results in growth retardation, muscle wasting and
      renal hypertrophy. This study tests the thesis that K deficiency leads to tissue
      distinct changes in the local IGF-I system and cell sensitivity to IGF-I that
      favors renal enlargement on the one hand and impaired muscle growth on the other.
      In rats after eight days of K deficiency, compared to pair-fed control rats, food
      utilization and muscle and body wt gain were attenuated while the kidneys
      enlarged. In muscle GH receptor and IGF-I gene expression, IGF-I peptide and IGF
      binding protein-5 (IGFBP) levels were decreased. Together with reduced food
      utilization, these changes may contribute to the attenuated muscle growth. In the
      enlarged kidneys despite a fall in IGF-I mRNA level, IGF-I peptide concentration
      was increased more than twofold. This increase in IGF-I could be caused by the
      increase in kidney IGFBP-1 gene and protein expression and the decrease in kidney
      IGF-I degrading activity noted in K deficiency. Treatment with IGF-I failed to
      induce body or muscle growth, but induced a further increase in kidney size and
      enlargement of the spleen. Thus, in K deficiency the spontaneous increase in IGF
      I levels in the kidney that is IGF-I sensitive may well be a cause of the renal
      hypertrophy.

PMID- 9263992
TI  - Expression of tissue type plasminogen activator and type 1 plasminogen activator
      inhibitor, and persistent fibrin deposition in chronic renal allograft failure.
AB  - Persistent fibrin deposition has been observed in kidneys undergoing chronic
      rejection, and has been suggested to contribute to the obliteration of the
      vasculature in these grafts. The mechanisms leading to it are not clear.
      Fibrinolysis, the process to remove fibrin in tissues, is initiated by tissue
      type plasminogen activator (tPA) and suppressed by type 1 plasminogen activator
      inhibitor (PAI-1). To investigate their roles in chronic rejection and fibrin
      deposition, we serially examined the expression of tPA and PAI-1 in an unmodified
      chronic rejection model, using a Fisher 344 to Lewis rat renal transplant, at 0,
      2, 4, 6, 10, 12, 16 and 20 weeks post-transplantation (N = 4 rats/time point in
      each group). We also analyzed fibrin deposition and the development of chronic
      changes in the grafts. Our results show that tPA was up-regulated only in the
      acute phase of rejection (P < 0.05), whereas PAI-1 was induced and persistently
      expressed during the progressive phase of chronic rejection, together with
      persistent fibrin deposition in the grafts. Immunohistochemistry showed PAI-1 was
      mainly localized to the damaged/proliferative vascular intima. The results
      suggest that persistent induction of PAI-1 may be responsible for the continuance
      of fibrin deposition, which is associated with irreversible damage and chronic
      graft loss.

PMID- 9263993
TI  - Nitric oxide and superoxide induced p53 and Bax accumulation during mesangial
      cell apoptosis.
AB  - During proliferative glomerulonephritis, the early phase of mesangiolysis is
      linked to increased nitric oxide (NO) production. NO. as well as superoxide (O2-)
      are inflammatory mediators that are generated by mesangial cells (MC) after
      cytokine stimulation. Added individually, both radicals induce MC apoptosis.
      However, the co-existence of a defined NO./O2- ratio is cross-protective.
      Apoptosis is characterized by specific features such as chromatin condensation,
      DNA strand breaks, and the occurrence of apoptotic regulating proteins. The tumor
      suppressor p53 and Bax (Bcl-2 associated protein x) are considered to be
      classical death promotors, which accumulate after toxic insults. To study p53 and
      Bax protein accumulation in NO. and/or O2(-)-induced apoptosis, we used the NO
      donor S-nitrosoglutathione (GSNO) and the redox cycler 2,3-dimethoxy-1,4
      naphtoquione (DMNQ). Both agonists initiated DNA fragmentation in a concentration
      dependent manner associated with transient p53 and Bax up-regulation. Co
      generation of NO./O2- resulted not only in reduced DNA fragmentation, but also in
      decreased Bax accumulation. Comparable to the NO./O2- co-generation, cytokines
      failed to induce apoptosis. In contrast, cytokines in combination with
      pyrrolidine dithiocarbamate, which blocks endogenous superoxide dismutase,
      allowed p53 and Bax accumulation as well as DNA fragmentation. Our results
      demonstrate p53 and Bax as early components in NO. and O2(-)-induced rat MC
      apoptosis and point to the NO./O2- interaction as a naturally occurring cell
      defense mechanism.

PMID- 9263994
TI  - Mesangial cell abnormalities in spontaneously hypertensive rats before the onset
      of hypertension.
AB  - To identify kidney biosynthetic abnormalities that may precede the onset of
      hypertension, we studied the expression of fibronectin (FN) and collagen IV (Coll
      IV) in young SHR (4 weeks of age) whose systolic blood pressure was normal and
      similar to that of age-matched control WKY rats. In isolated glomeruli the level
      of FN protein assessed by immunoblotting tended to be lower in the SHR than in
      the WKY rats. By Northern analysis the FN/actin mRNA ratio was significantly
      lower in glomeruli from SHR (0.56 +/- 0.47) than in glomeruli from WKY rats (2.0
      +/- 0.8). These abnormalities were maintained in vitro since the expression of FN
      was significantly lower in SHR than in WKY cultured mesangial cells (FN/actin
      mRNA ratio = 0.84 +/- 0.46 vs. 1.9 +/- 0.7, P = 0.029). No differences in Coll IV
      mRNA or protein levels were observed in SHR glomeruli and mesangial cells when
      compared with WKY rats. The levels of aortic FN and Coll IV mRNAs were not
      different in SHR and WKY rats. In addition, mesangial cells from SHR showed a
      significantly higher growth rate than those from WKY. The biosynthetic and
      proliferative abnormalities observed in the SHR mesangial cells appear to reflect
      genetic characteristics, and could provide novel insights into cellular
      mechanisms linking the genetics of hypertension with predisposition to glomerular
      pathology.

PMID- 9263995
TI  - Podocytes are the major source of IL-1 alpha and IL-1 beta in human
      glomerulonephritides.
AB  - To address the question of in situ production of IL-1 alpha and IL-1 beta in
      proliferative and non-proliferative forms of human glomerulonephritis (GN), we
      performed immunocytochemical and in situ hybridization studies on renal biopsies
      from patients with mesangial IgA-GN (N = 38), idiopathic membranous GN (MGN; N =
      12), minimal change disease (MCD; N = 9), focal segmental glomerulosclerosis
      (FSGS; N = 5) and acute endocapillary GN (AGN; N = 3). Normal kidneys (N = 10)
      served as controls. Concomitantly, the expression of IL-1 receptor type I (IL-1
      RI), IL-1 receptor type II (IL-1 RII) and of IL-1 receptor antagonist (IL-1 RA)
      was analyzed. Antibodies against antigens expressed on podocytes (PP-44),
      endothelial cells (CD31) and monocytes/macrophages (CD11b, CD14, CD68) were
      applied to attribute the expression of IL-1/IL-1 related peptides to intrinsic
      glomerular and/or blood-derived infiltrating cells. Our results demonstrate that
      IL-1 RII is constitutively expressed on endothelial cells, and its expression can
      be induced in proximal tubular cells and in the interstitium. In diseased
      glomeruli podocytes are capable of producing IL-1 alpha/beta. In MGN and
      MCD/FSGS, the expression of both IL-1 forms is particularly noted in early stages
      of the disease and is not only accompanied by a marked reactivity for IL-1 RI,
      but also for IL-1 RA. In segmental sclerosing lesions in FSGS and in IgA-GN with
      marked glomerular proliferation and/or sclerosis, a reduced expression of the PP
      44 antigen and a diminished ability of podocytes to produce IL-1/IL-1 related
      peptides are noted. These results suggest that intrinsic glomerular production of
      IL-1 may be of relevance for the protection of glomeruli from continuing injury.

PMID- 9263996
TI  - Cyclin kinase inhibitors are increased during experimental membranous
      nephropathy: potential role in limiting glomerular epithelial cell proliferation
      in vivo.
AB  - The inadequate proliferative response of the visceral glomerular epithelial cell
      (GEC) following injury in vivo may contribute to the development of progressive
      glomerulosclerosis in many forms of glomerular disease. Cell proliferation is
      ultimately controlled by cell-cycle regulatory proteins, including cyclins that
      bind to cyclin dependent kinases (CDK), and the active complex formed is
      necessary for progression through the cell-cycle. By inhibiting cyclin-CDK
      complexes, cyclin kinase inhibitors arrest the cell-cycle and prevent
      proliferation. To determine the mechanisms that may be responsible for the lack
      of GEC proliferation in vivo, we examined GEC expression of specific cell-cycle
      proteins in normal rats and in the passive Heymann nephritis (PHN) model of
      membranous nephropathy, where the GEC are the target of complement-mediated
      injury. Following antibody deposition and complement activation there was a
      marked up-regulation in the cyclin kinase inhibitors p21 and p27 in rats with
      PHN. By associating with cyclin A-CDK2 complexes, p21 and p27 limited the kinase
      activity of CDK2. Giving bFGF to rats with PHN was associated with an increase in
      GEC mitosis and ploidy and a decrease in expression of p21, but not CDK2 or p27.
      Furthermore, apoptosis was not present in PHN, but was increased in rats given
      bFGF. In conclusion, this study shows that the low proliferative capacity of the
      GEC in vivo in response to immune injury may be due to an increase in the
      expression of specific cyclin kinase inhibitors. The increase in mitosis in PHN
      rats given bFGF may be due to a decrease in p21. Thus, changes in cell cycle
      regulatory proteins may regulate the response of GEC to injury and underlie the
      development of progressive glomerulosclerosis in diseases of the GEC.

PMID- 9263997
TI  - Immunodissection of the human proximal nephron: flow sorting of S1S2S3, S1S2 and
      S3 proximal tubular cells.
AB  - We report on the use of several proximal tubular cell (PTC) surface markets and
      corresponding antibodies in fluorescence-activated cell sorting (FACS), and their
      ability to identify and flow sort cells of defined proximal tubular origin
      (S1S2S3) or of defined proximal subsegmental origin (S1S2 only/S3 only). We
      tested monoclonal/polyclonal antibodies directed against five different surface
      peptidases [leucine aminopeptidase (LAP), neutral endopeptidase 24.11 (NEP),
      dipeptidyl peptidase IV (DPPIV), aminopeptidase A (APA) and gamma-glutamyl
      transferase (gamma-GT)], the S3 segment-specific marker intestinal type alkaline
      phosphatase (iAP) and an S1S2 marker (TN20-antigen), originally proposed as a
      surface marker for interstitial fibroblasts. Segmental (proximal tubular vs.
      distal tubular) and proximal subsegmental (S1S2 vs. S3) expression of all five
      surface peptidases and TN20 antigen were first assessed by comparing
      immunohistochemical staining on normal human kidney tissue with staining for well
      known segment-specific differentiation markers (intestinal type alkaline
      phosphatase, Tamm-Horsfall protein) on adjacent sections. All five peptidases
      were found to be expressed to a certain degree in all subsegments (S1 S2 and S3)
      of the proximal nephron, whereas expression was never seen in the more distal
      parts of the nephron. Flow cytometry was performed on cells obtained following
      gradient purification of collagenase-digested human renal tissue. Labeling cells
      for expression of LAP, NEP or DPPIV resulted in high yields of specifically
      labeled PTC (S1S2S3 origin). Labeling with anti-LAP resulted in the clearest
      distinction between positive and negative cell subpopulations, and therefore LAP
      was considered the best PTC marker for use in FACS. iAP histochemical staining on
      sorted cells showed that flow sorting with monoclonal antibody (moAb) 250 (anti
      intestinal type alkaline phosphatase) allowed sorting of S3 cells with > 90%
      purity. Likewise, moAb TN20 enabled us to obtain a highly purified S1S2
      population as confirmed by the absence of iAP on sorted cells.

PMID- 9263998
TI  - Carnitine palmitoyl-transferase enzyme inhibition protects proximal tubules
      during hypoxia.
AB  - The role of inhibition of the CPT enzymes responsible for accumulation of long
      chain acylcarnitines (LCAC) during hypoxia in the proximal tubule has not been
      previously examined. We have characterized CPT enzyme activities in mitochondrial
      fractions of rabbit proximal tubules. Malonyl CoA-sensitive CPT I activity (1.1
      +/- 0.3 nmol/min/mg protein), and detergent-solubilized, malonyl CoA-insensitive
      CPT II activity (2.3 +/- 0.4 nmol/min/mg protein) were readily detected in
      proximal tubule mitochondrial fractions. Subjecting rabbit proximal tubules to
      various periods of hypoxia did not significantly change mitochondrial CPT I or
      CPT II activities. Thirty minutes of hypoxia resulted in an increase in
      lysophospholipid mass from 440 +/- 105 to 720 +/- 93 pmol/mg protein, N = 5, LCAC
      mass from 79 +/- 11 to 618 +/- 34 pmol/mg protein, N = 5, and lactate
      dehydrogenase (LDH) release from 9 +/- 1% to 46 +/- 3%, N = 8. Pretreatment of
      proximal tubules with two different CPT inhibitors, glybenclamide (Glyb) 400
      microM and oxfenicine (Oxfe) 1 mM, resulted in reduction in the magnitude of
      hypoxia-induced lysophospholipid formation 490 +/- 160 (Glyb), 342 +/- 150
      pmol/mg protein (Oxfe), N = 4, hypoxia-induced LCAC formation 295 +/- 27 (Glyb),
      128 +/- 16 pmol/mg protein (Oxfe). N = 5, and LDH release 25 +/- 1% (Glyb) and 19
      +/- 2% (Oxfe), N = 8. The protective effect of CPT inhibition was also associated
      with increased production of lactate suggesting the modulation of a substrate
      mediated metabolic switch. Immunoblots demonstrated that hypoxia caused a time
      dependent hydrolysis of fodrin-alpha subunit and that CPT inhibition protected
      against hypoxia-induced fodrin proteolysis. These data suggest a unifying
      hypothesis that links phospholipase A2 (PLA2) activation, and hypoxia-mediated
      fodrin proteolysis to the proximal tubule mitochondrial CPT system. I propose
      that CPT inhibition may represent a novel mechanism to ameliorate proximal tubule
      cell death during hypoxia.

PMID- 9263999
TI  - Role of caspases (ICE/CED 3 proteases) in DNA damage and cell death in response
      to a mitochondrial inhibitor, antimycin A.
AB  - Caspases (ICE/ Ced3 proteases) are a closely related family of cysteine proteases
      that play a key role in apoptotic cell death. We examined the role of caspases in
      DNA damage and cell death in response to the mitochondrial inhibitor, antimycin
      A. LLC-PK1 cells contain caspase activity that was markedly inhibited by cleavage
      site-based peptide inhibitors of caspases but not by inhibitors of serine,
      cysteine, aspartate or metalloproteinases. The caspase activity increased within
      five minutes of exposure to antimycin A, preceding any evidence of DNA damage and
      cell death. The specific caspase inhibitors. Ac-Tyr-Val-Ala-Asp-aldehyde
      (inhibitor I) and Ac-Asp-Glu-Val-Asp-aldehyde (inhibitor II) prevented, in a dose
      dependent manner, antimycin A-induced DNA strand breaks as determined by DNA
      unwinding assay (residual double stranded DNA in control, 94 +/- 2%; antimycin A
      alone, 48 +/- 3%; antimycin A + inhibitor I at 50 microM, 93 +/- 2%; antimycin A
      + inhibitor II at 50 microM, 89 +/- 5%; N = 3 to 4, P < 0.001). These inhibitors
      also prevented antimycin A-induced DNA fragmentation as determined by agarose gel
      electrophoresis and by in situ labeling of cell nuclei by the terminal
      deoxynucleotidyl transferase (TdT) nick end labeling (TUNEL) method. The caspase
      inhibitors markedly prevented antimycin A-induced cell death in a dose-dependent
      manner as measured by trypan blue exclusion (control 6 +/- 1%, antimycin A alone
      40 +/- 1%, antimycin A + inhibitor I at 50 microM 16 +/- 1%, antimycin A +
      inhibitor II at 50 microM 16 +/- 1%; N = 4 to 7, P < 0.001). These data indicate
      that the caspase family of enzymes play an important role in DNA damage and cell
      death in response to the mitochondrial inhibitor, antimycin A.

PMID- 9264000
TI  - Effect of acute increases in filtered HCO3- on renal hydrogen transporters: II.
      H(+)-ATPase.
AB  - Adaptive increases in renal bicarbonate reabsorption occur in response to acute
      increases in filtered bicarbonate (FLHCO3). In a previous study, we showed that
      an increase in FLHCO3 induced by plasma volume expansion increased the Vmax for
      Na+/H+ exchange activity in renal cortical brush border membrane vesicles (BBMV),
      providing a potential mechanism for the adaptive increase in HCO3- reabsorption.
      The present studies were undertaken to determine whether the increase in FLHCO3
      induced by plasma expansion also stimulates the other major H+ transporter in
      cortical BBMV, the H(+)-ATPase. H(+)-ATPase activity was assessed in BBMV
      obtained from hydropenic and plasma expanded Munich-Wistar rats, using a NADH
      linked ATPase assay. H(+)-ATPase activity was measured as the ouabain and
      oligomycin-insensitive, bafilomycin A1-sensitive component of total ATPase
      activity. Acute plasma expansion doubled single nephron FLHCO3, and this change
      was associated with a 64% increase in the Vmax for H(+)-ATPase activity, with no
      change in apparent Km. The Vmax for H(+)-ATPase activity correlated directly with
      whole kidney GFR and FLHCO3 (r = 0.68 and 0.72, respectively), and with single
      nephron GFR and FLHCO3 (r = 0.76 and 0.80, respectively). Thus, the mechanism for
      the adaptive increase in proximal tubular HCO3- reabsorption that occurs in
      response to acute increases in FLHCO3 appears to be related to increased activity
      of both H(+)-ATPase and Na+/H+ exchange in the apical membrane of the proximal
      tubule epithelium.

PMID- 9264001
TI  - Moxonidine inhibits Na+/H+ exchange in proximal tubule cells and cortical
      collecting duct.
AB  - The imidazoline receptor agonist moxonidine has been recently introduced as an
      antihypertensive therapy. Imidazoline specific binding sites have also been found
      in the kidney. Moxonidine induced natriuresis and diuresis in clearance studies
      in rats. Related substances such as various guanidinium derivatives have been
      shown to inhibit Na+/H+ exchange in several preparations. We therefore examined
      whether the renal effects of moxonidine could be mediated by an inhibition of the
      Na+/H+ exchanger. Intracellular pH (pHi) was measured microfluorimetrically with
      BCECF in proximal LLC-PK1 cells and in the principal cells of rat cortical
      collecting ducts (CCD). In LLC-PK1 cells moxonidine (10 mumol/liter) had no
      effect on the basal pH1; however, it reduced the Na+/H+ activity reversibly by 43
      +/- 4% (N = 26) when the exchanger was activated by cellular acidification. In
      rat CCD cells moxonidine slightly decreased basal pHi by 0.08 +/- 0.03 pH units
      (N = 12). After acidification the recovery rate of pHi was reduced with
      moxonidine by 45 +/- 6% (N = 18). The effects of moxonidine could be mimicked in
      both cell types by inhibitors of the Na+/H+ exchanger (HOE 694, amiloride). In
      the presence of the imidazoline receptor antagonist idazoxan (10 mumol/liter) the
      effects of moxonidine were almost completely inhibited. The alpha 2-antagonist
      yohimbine (10 mumol/liter) did not significantly alter the effects of moxonidine
      in both cell types. These data suggest that in LLC-PK1 and in rat CCD cells,
      Na+/H+ is inhibited by moxonidine via an activation of the imidazoline receptor.

PMID- 9264002
TI  - Glomerular and vascular tissues do not down-regulate nitric oxide synthesis
      during protracted endotoxemia.
AB  - Down-regulation of cytokines is implicated as an important component of the
      phenomenon of tolerance to bacterial products in humans and animals. Since many
      effects of endotoxin and cytokines are mediated by nitric oxide, this study was
      designed to evaluate in vivo the L-arginine:NO pathway in endotoxin tolerance.
      Sublethal injections of E. coli lipopolysaccharide (LPS, 1 mg/kg body wt, i.p.)
      were given to rats daily for five days. Blood levels of NO2-/NO3-, stable
      metabolites of nitric oxide (NO), significantly increased on day 1 (baseline,
      89.64 +/- 40, day 1, 260.32 +/- 36 nmol/ml; P < 0.05) but returned to baseline
      levels on day 5 (77.60 +/- 5 nmol/ml). However, urinary NO2-/NO3- remained
      significantly elevated several-fold throughout the study period (baseline, 121.25
      +/- 11.4, day 1, 899.35 +/- 15.8, day 5, 250.23 +/- 21.4 nmol/hr/100 g body wt).
      Glomeruli and aortae obtained from these rats showed increased NO production that
      was maintained at similar levels even at day 5 (glomeruli: control, 0.01 +/- 0.0,
      day 1, 22.4 +/- 0.3, and day 5, 22.0 +/- 2.5, P < 0.05 vs. control; aortae;
      control, 0.01 +/- 0.0, day 1, 4.3 +/- 2.2, and day 5, 5.4 +/- 1.0 nmol/hr/mg
      protein, P < 0.05 vs. control, respectively); this further increased
      significantly in response to in vitro LPS challenge. However, peritoneal
      macrophages, liver and spleen showed an initial increase in NO production that
      decreased significantly by the fifth day of LPS and could not be further
      stimulated by in vitro LPS challenge. Thus, in vivo NO synthesis is down
      regulated during protracted LPS. Our results show that the process is relatively
      specific to the liver, spleen and macrophages, and is qualitatively and
      quantitatively different in vascular tissues such as aortae and glomeruli.

PMID- 9264004
TI  - Angiotensin-converting enzyme gene polymorphism in non-insulin dependent diabetes
      mellitus and its relationship with diabetic nephropathy.
AB  - Previous studies have shown that the angiotensin-converting enzyme (ACE) gene
      polymorphism is associated with an increased risk of vascular disease in non
      diabetic patients. The present study was conducted on 509 NIDDM patients who
      underwent a screening test to determine their ACE genotype for the Appropriate
      Blood Pressure Control in Diabetes (ABCD) Trial. Various baseline indices were
      correlated with the three ACE polymorphisms. The genotype was determined through
      polymerase chain reaction amplification of the angiotensin-converting enzyme
      polymorphism. The univariate relationship between the presence of the DD genotype
      with nephropathy as measured by urinary albumin excretion (UAE), and a history
      coronary artery disease (CAD) was then examined. Finally, a multiple model for
      each UAE and CAD was created so as to determine the independent effects of the
      presence of the DD genotype on each diabetic complication. Univariately, the
      presence of the DD genotype was associated with diabetic nephropathy.
      Furthermore, in a multiple model predicting diabetic nephropathy, the presence of
      the DD genotype was independently associated with diabetic nephropathy (odds
      ratio = 2.8, 95% confidence interval 1.4 to 5.5) but not CAD. Thus, the ACE DD
      genotype in 509 non-Hispanic white NIDDM patients in a metropolitan area in the
      U.S. was independently associated with the presence of diabetic nephropathy and,
      therefore, may be potentially used as a marker for NIDDM patients at risk for
      developing diabetic nephropathy.

PMID- 9264003
TI  - Physiology and biochemistry of endothelial function in children with chronic
      renal failure.
AB  - Premature atherosclerosis is a major cause of morbidity and mortality in chronic
      renal failure (CRF). Endothelial dysfunction is a key early event in
      atherogenesis. The aim of this study was to assess the effect of CRF on
      endothelial function using physiological and biochemical measures. To focus on
      the effect of CRF itself, 23 children (matched with 23 controls for age and
      vessel diameter) were selected because they were normotensive, had normal total
      cholesterol (TC) levels, and were not on vasoactive drugs. Their mean (range) age
      was 12.0 (7.8 to 17.0) years; GFR 17.5 (8.8 to 34.5) ml/min/1.73 m2. The
      physiology of endothelial function in the brachial artery was assessed using high
      resolution ultrasound by measuring its diameter at rest, during reactive
      hyperemia (endothelium dependent dilation) and after sublingual glyceryl
      trinitrate (GTN; endothelium independent dilation). Nitric oxide (NO) metabolites
      and endogenous NO synthetase (eNOS) inhibitors were measured as an assessment of
      endothelial metabolism. Brachial artery dilation to flow [FMD, mean (SEM)%] was
      reduced in CRF to 4.9 (0.6) and controls 8.6 (0.6), P < 0.0001. In contrast, the
      response to GTN was similar in both groups: CRF 25.1 (1.6), controls 23.3 (1.2),
      P = 0.31. There was no difference in TC, low density lipoprotein (LDL) or high
      density lipoprotein (HDL) between the patients and the controls. Triglycerides
      (TG) were higher in the patients but within the normal range. Antibodies against
      oxidized LDL (ox-LDL) were high in CRF. Endogenous NOS inhibitors were high in
      CRF, and intermediate NO metabolites were low. There was no correlation between
      FMD of the brachial artery and lipid subfractions, or with NO metabolites or eNOS
      inhibitors. Endothelium dependent dilation of the brachial artery is impaired in
      children with CRF who do not have co-existing risk factors for atherosclerosis.
      This may represent early evidence of atherogenic vascular disease.

PMID- 9264005
TI  - Urinary tract morbidity due to Schistosoma haematobium infection in Mali.
AB  - A total of 824 Malian villagers in a region endemic for Schistosoma (S.)
      haematobium were examined clinically, parasitologically and by abdominal
      ultrasound. Systematic schistosomicidal treatment had never been applied to this
      population. Prevalence of S. haematobium infection ranged from 77% in adolescents
      to 51% in adults older than 40 years. Intensity of infection was generally mild,
      91% of all patients excreting less than 100 ova/10 ml urine. Bladder wall
      enlargement and irregularities, bladder masses, pseudopolyps and dilation of the
      upper urinary tract were found ultrasonographically in about one third of
      infected individuals. Bladder lesions were more frequent in children than in
      adults and correlated with the intensity of infection in younger age groups only.
      Hydronephrosis was rare (7 of 824) and never seen in uninfected individuals.
      Prevalence of urinary tract pathology dropped significantly with age (P < 0.001)
      and was lowest in patients older than 40 years. Logistical regression identified
      age and infection as independent parameters affecting the prevalence of urinary
      tract pathology (P < 0.001). We conclude that Schistosoma haematobium infection
      causes substantial morbidity in children and younger adults. The reduction of
      urinary tract morbidity with age despite a considerable prevalence of infection
      in older age groups suggests spontaneous resolution during adulthood in most
      cases.

PMID- 9264006
TI  - Increased incidence of glomerulonephritis following spleno-renal shunt surgery in
      non-cirrhotic portal fibrosis.
AB  - In a prospective study of 200 non-cirrhotic portal fibrosis (NCPF) patients, 7%
      had mild proteinuria and their renal biopsies showed mild mesangial proliferative
      glomerulonephritis (mes-PGN). The remaining 93% biopsies were normal. However,
      following the insertion of a spleno-renal shunt (SRS) for portal hypertension 32%
      of these patients developed nephrotic syndrome in five years. Renal histology
      revealed mesangiocapillary glomerulonephritis (MCGN) (18.5%), mes-PGN (9%),
      minimal change nephropathy (3%), and chronic sclerosing GN (1.5%).
      Immunofluorescence showed granular deposition of IgA and C3. IgA2 was the
      predominant form of Ig in the glomerular deposits, indicating that IgA in the
      immune complexes was derived from the gastrointestinal tract. Electron microscopy
      revealed electron dense deposits in the mesangium. In contrast to the NCPF
      patients who underwent a SRS for portal hypertension, the 200 patients in our
      study who underwent spleno-renal shunting because of extra hepatic portal
      obstruction did not have renal disease, nor did they develop renal disease during
      the five-year post-operative follow-up. Fifty percent of the glomerulonephritis
      (GN) in the NCPF group progressed to renal failure in five years; 46.6% continued
      to have proteinuria. Low serum complement, C3 (40%) and circulating immune
      complexes (14.8%) were detected in the glomerulonephritis group. Our study shows
      that: (i) there is a high rate of the occurrence of GN following SRS in NCPF
      patients, but not in those with normal livers; (ii) the type of GN is primarily
      IgA nephropathy; and (iii) the GN could be the result of defective hepatic
      reticuloendothelial function in the NCPF group that is worsened by the shunting
      procedure.

PMID- 9264007
TI  - Dietary protein, urea nitrogen appearance and total nitrogen appearance in
      chronic renal failure and CAPD patients.
AB  - This study was carried out to examine the mathematical relationships between the
      urea nitrogen appearance (UNA), total nitrogen appearance (TNA) and dietary
      nitrogen intake (DNI) in patients with chronic renal failure. Studies were
      conducted in 20 nondialyzed patients with advanced chronic renal failure (CRF)
      who were fed 27 constant protein diets for 24.8 +/- 9.5 days (SD) and eight
      patients undergoing continuous ambulatory peritoneal dialysis (CAPD), who
      ingested 13 constant protein diets for 20.3 +/- 4.9 days. All patients lived in a
      hospital research ward throughout the study and underwent full nitrogen balance
      measurements. Data were analyzed after patients attained equilibrium or near
      equilibrium with each dietary protein intake. In the CRF patients, using the mean
      values obtained during the equilibrium phase, there was a direct and precise
      correlation between the TNA and UNA, where TNA g/day = 1.19 UNA g/day + 1.27
      g/day, r = 0.948. The correlation between DNI and UNA was also highly
      significant, but less precise, with somewhat greater 95% confidence intervals:
      DNI g/day = 1.20 UNA g/day + 1.74 g/day, r = 0.865. The relationship between DNI
      and TNA was not much more precise: DNI g/day = 0.97 TNA g/day + 0.65 g/day, r =
      0.880. With the CAPD patients, the relationships were as follows: TNA g/day =
      0.94 UNA g/day + 5.54 g/day, r = 0.956; DNI g/day = 0.97 UNA g/day + 6.80 g/day,
      r = 0.705; DNI g/day = 1.07 TNA g/day + 0.63 g/day, r = 0.760. For the CAPD
      patients, the lowest 95% confidence intervals were also found for the correlation
      between TNA and UNA. Thus, in both CRF and CAPD patients, the TNA is highly and
      precisely correlated with the UNA. The DNI is also significantly correlated with
      UNA and TNA, but the relationship is less precise. In both of these two groups of
      patients, the difference between the regression equations for TNA versus UNA and
      DNI versus UNA was, to a substantial degree, accounted for by the intercept.

PMID- 9264008
TI  - Kinetic basis of hyperhomocysteinemia in patients with chronic renal failure.
AB  - We investigated the elimination of total homocysteine (tHcy) from plasma after
      peroral homocysteine (Hcy) loading in eight patients with chronic renal failure.
      Data on bioavailability and distribution volume were obtained from two patients
      and two healthy controls by performing both intravenous and peroral Hcy loading.
      Response to high-dose folic acid was studied in six cases. Mean (SD) basal plasma
      tHcy was 27.4 (11.0) microM at inclusion. The half-life and the area under the
      curve were about four times higher, and clearance was reduced to 29.8% compared
      to controls. High-dose folic acid had no influence on half-life for tHcy, but the
      basal tHcy level declined by 26.8%. The reduction in tHcy was particularly
      pronounced in three patients with low-normal serum folate, and the enhanced
      methionine response to Hcy loading after folic acid suggested improved Hcy
      remethylation in tissues. In conclusion, patients with renal failure had markedly
      reduced clearance of tHcy from plasma, which probably accounts for their
      hyperhomocysteinemia. High-dose folic acid reduces fasting tHcy by improving
      tissue Hcy remethylation without affecting the low renal clearance of tHcy.

PMID- 9264009
TI  - Insulin resistance in adult polycystic kidney disease.
AB  - Adult polycystic kidney disease (APKD) is a common hereditary disease with renal
      and extra-renal manifestations. There are at least three genes responsible for
      this disease. The polycystic kidney disease 1 (PKD1) gene product is a membrane
      protein involved in cell-cell and cell-matrix interactions and has a widespread
      tissue distribution. Abnormal membrane fluidity in erythrocytes from APKD
      patients is due to altered membrane proteins. Membrane fluidity of mononuclear
      cells is related to whole body insulin sensitivity. Insulin sensitivity might
      therefore be disturbed in APKD if the erythrocyte membrane abnormality is also
      present in other cells. Therefore, we investigated insulin sensitivity in 15 APKD
      patients and 20 normal subjects matched for age and sex. Insulin sensitivity was
      assessed by a short insulin tolerance test to derive the first-order rate
      constant for the disappearance of glucose (Kitt) and mononuclear leukocyte
      membrane fluidity was measured by fluorescence anisotropy. The Kitt value (%
      mmol.liter-1.min-1) was lower in APKD patients than in normal subjects [median
      (range) 2.2 (1.5 to 6.3) vs. 4.1 (2.0 to 5.4). P < 0.001]. Fasting plasma insulin
      concentrations were negatively correlated with the Kitt values (r = -0.66, P <
      0.001). Core region anisotropy was significantly lower (higher fluidity) in
      leukocytes from APKD patients [mean (SEM) 0.164 (0.003) vs. 0.174 (0.001), P <
      0.001]. Insulin sensitivity was positively correlated with the fluorescence
      anisotropy of the core region of leukocyte membranes (r = 0.81, P = 0.0001). In
      conclusion, APKD patients were insulin resistant and some patients were
      hyperinsulinemic, which may indicate increased cardiovascular risk. The cellular
      basis of the insulin resistance may be directly related to the proteins causing
      the disease or to the general change in membrane properties.

PMID- 9264010
TI  - Galactose-deficient IgA1 in sera of IgA nephropathy patients is present in
      complexes with IgG.
AB  - IgA1 proteins from sera of patients with IgA nephropathy (IgAN) are
      galactosylated to a lesser degree than those from healthy controls. The increased
      reactivity of intact or de-sialylated serum IgA1 with N-acetylgalactosamine
      (GalNAc)-specific lectins, Helix aspersa (HAA) and Caragana arborescens (CAA) and
      de-sialylated IgA1 with Helix pomatia (HPA) and Bauhinia purpurea (BPA) indicated
      that the Gal deficiency is in glycans located in the hinge region of IgA1
      molecules. De-sialylated IgA from sera of 81 IgAN patients bound biotin-labeled
      lectin HAA more effectively than did de-sialylated IgA from 56 healthy controls
      (P < 0.0001). Similar results were observed for 67 IgAN patients and 52 controls
      with second lectin, CAA (P < 0.001). The binding patterns for 9 patients with
      mesangial proliferative glomerulonephritis of non-IgA origin were similar to
      those for controls. Incompletely galactosylated IgA1 capable of binding GalNAc
      specific lectins was detected in complexes with IgG as demonstrated by ELISA,
      size-exclusion chromatography and sucrose gradient ultracentrifugation. The
      formation of IgA1-IgG complexes may affect the serum level of IgA1 by reducing
      the rate of its elimination and catabolic degradation by the liver.

PMID- 9264011
TI  - Mutation (677 C to T) in the methylenetetrahydrofolate reductase gene aggravates
      hyperhomocysteinemia in hemodialysis patients.
AB  - Hyperhomocysteinemia is frequent in hemodialysis patients and represents an
      independent risk factor for vascular disease in these patients. Elevated total
      homocysteine (tHcy) plasma levels can results from defective remethylation of Hcy
      to methionine due to decreased activity of the enzyme methylenetetrahydrofolate
      reductase (MTHFR). A genetic aberration in the MTHFR gene (677 C to T
      substitution) has been shown to result in reduced MTHFR activity. We tested the
      hypothesis that elevation of tHcy plasma levels in hemodialysis patients is
      influenced by the 677 C to T mutation of the MTHFR gene and examined the relation
      of the genotype with tHcy, folate and vitamin B12 plasma levels in these
      patients. The allelic frequency of the MTHFR mutation was evaluated in 203
      patients maintained on chronic hemodialysis treatment. Total Hcy, folate, vitamin
      B12 levels and the MTHFR mutation were analyzed in 69 of the 203 patients and in
      69 age- and sex-matched healthy control subjects. The allelic frequency of the
      677 C to T transition in the MTHFR gene in hemodialysis patients was 34.7% versus
      35.5% in healthy controls. Of 203 patients 26 (12.8%) were homozygous for the
      mutation (+/+) versus 10.2% in healthy subjects. The heterozygous (+/-) genotype
      was identified in 43.8% of patients versus 50.7% in controls. The mean tHcy level
      in hemodialysis patients was 28.7 +/- 11.0 mumol/liter versus 10.0 +/- 3.0
      mumol/liter in control subjects. The mean tHcy levels were 36.4 +/- 13.4
      mumol/liter in (+/+) patients and 12.2 +/- 4.5 mumol/liter in (+/+) controls,
      28.7 +/- 10.8 mumol/liter in (+/-) patients and 9.9 +/- 2.7 mumol/liter in (+/-)
      controls and 25.4 +/- 8.5 mumol/liter in (-/-) hemodialysis patients versus 9.7
      +/- 2.8 mumol/liter in (-/-) controls: There was no significant difference of
      folate and vitamin B12 concentrations in patients and controls with different
      MTHFR genotypes. Analysis of covariance including age, gender, folate
      concentrations, vitamin B12 levels, albumin and creatinine as covariables
      revealed a significant influence of the (+/+) genotype, albumin and folate status
      on tHcy levels in hemodialysis patients. Together, our data demonstrate that the
      extent of hyperhomocysteinemia in hemodialysis patients is not only the result of
      uremia or folate status, but is also genetically determined by the (+/+) MTHFR
      genotype. The presence of the 677 C to T mutation in the MTHFR gene does not
      appear to represent a risk factor for development of end-stage renal disease.

PMID- 9264012
TI  - Outcomes of single organism peritonitis in peritoneal dialysis: gram negatives
      versus gram positives in the Network 9 Peritonitis Study.
AB  - The use of the "peritonitis rate" in the management of patients undergoing
      peritoneal dialysis is assuming importance in comparing the prowess of
      facilities, care givers and new innovations. For this to be a meaningful outcome
      measure, the type of infection (causative pathogen) must have less clinical
      significance than the number of infections during a time interval. The natural
      history of Staphylococcus aureus, pseudomonas, and fungal peritonitis would not
      support that the outcome of an episode of peritonitis is independent of the
      causative pathogen. Could this concern be extended to other more frequently
      occurring pathogens? To address this, the Network 9 Peritonitis Study identified
      530 episodes of single organism peritonitis caused by a gram positive organism
      and 136 episodes caused by a single non-pseudomonal gram negative (NPGN)
      pathogen. Coincidental soft tissue infections (exit site or tunnel) occurred
      equally in both groups. Outcomes of peritonitis were analyzed by organism
      classification and by presence or absence of a soft tissue infection. NPGN
      peritonitis was associated with significantly more frequent catheter loss,
      hospitalization, and technique failure and was less likely to resolve regardless
      of the presence or absence of a soft tissue infection. Hospitalization and death
      tended to occur more frequently with enterococcal peritonitis than with other
      gram positive peritonitis. The outcomes in the NPGN peritonitis group were
      significantly worse (resolution, catheter loss, hospitalization, technique
      failure) compared to coagulase negative staphylococcal or S. aureus peritonitis,
      regardless of the presence or absence of a coincidental soft tissue infection.
      Furthermore, for the first time, the poor outcomes of gram negative peritonitis
      are shown to be independent of pseudomonas or polymicrobial involvement or soft
      tissue infections. The gram negative organism appears to be the important factor.
      In addition, the outcome of peritonitis caused by S. aureus is worse than that of
      other staphylococci. Thus, it is clear that all peritonitis episodes cannot be
      considered equivalent in terms of outcome. The concept of peritonitis rate is
      only meaningful when specific organisms are considered.

PMID- 9264013
TI  - Precise quantification of dialysis using continuous sampling of spent dialysate
      and total dialysate volume measurement.
AB  - The "gold standard" method to evaluate the mass balances achieved during dialysis
      for a given solute remains total dialysate collection (TDC). However, since
      handling over 100 liter volumes is unfeasible in our current dialysis units,
      alternative methods have been proposed, including urea kinetic modeling, partial
      dialysate collection (PDC) and more recently, monitoring of dialysate urea by on
      line devices. Concerned by the complexity and costs generated by these devices,
      we aimed to adapt the simple "gold standard" TDC method to clinical practice by
      diminishing the total volumes to be handled. We describe a new system based on
      partial dialysate collection, the continuous spent sampling of dialysate (CSSD),
      and present its technical validation. Further, and for the first time, we report
      a long-term assessment of dialysis dosage in a dialysis clinic using both the
      classical PDC and the new CSSD system in a group of six stable dialysis patients
      who were followed for a period of three years. For the CSSD technique, spent
      dialysate was continuously sampled by a reversed automatic infusion pump at a
      rate of 10 ml/hr. The piston was automatically driven by the dialysis machine:
      switched on when dialysis started, off when dialysis terminated and held during
      the by pass periods. At the same time the number of production cycles of
      dialysate was monitored and the total volume of dialysate was calculated by
      multiplying the volume of the production chamber by the number of cycles. Urea
      and creatinine concentrations were measured in the syringe and the masses were
      obtained by multiplying this concentration by the total volume. CSSD and TDC were
      simultaneously performed in 20 dialysis sessions. The total mass of urea removed
      was calculated as 58038 and 60442 mmol/session (CSSD and TDC respectively; 3.1 +/
      1.2% variation; r = 0.99; y = 0.92x -28.9; P < 0.001). The total mass of
      creatinine removed was 146,941,143 and 150,071,195 mumol/session (2.2 +/- 0.9%
      variation; r = 0.99; y = 0.99x + 263; P < 0.001). To determine the long-term
      clinical use of PDC and CSSD, all the dialysis sessions monitored during three
      consecutive summers with PDC (during 1993 and 1994) and with CSSD (1995) in six
      stable dialysis patients were included. The clinical study comparing PDC and CSSD
      showed similar urea removal: 510 +/- 59 during the first year with PDC and 516 +/
      46 mmol/dialysis session during the third year, using CSSD. Protein catabolic
      rate (PCR) could be calculated from total urea removal and was 1.05 +/- 0.11 and
      1.05 +/- 0.09 g/kg/day with PDC and CSSD for the same periods. PCR values were
      clearly more stable when calculated from the daily dialysate collections than
      when obtained with urea kinetic modeling performed once monthly. We found that
      CSSD is a simple and accurate method to monitor mass balances of urea or any
      other solute of clinical interest. With CSSD, dialysis efficacy can be monitored
      at every dialysis session without the need for bleeding a patient. As it is
      external to the dialysis machine, it can be attached to any type of machine with
      a very low cost. The sample of dialysate is easy to handle, since it is already
      taken in a syringe that is sent directly to the laboratory. The CSSD system is
      currently in routine use in our unit and has demonstrated its feasibility, low
      cost and high clinical interest in monitoring dialysis patients.

PMID- 9264014
TI  - Lupus nephritis.

PMID- 9264015
TI  - Complexities of DNA base excision repair in mammalian cells.

PMID- 9264016
TI  - Resistance to tobamoviruses in transgenic tobacco plants expressing the coat
      protein gene of pepper mild mottle virus (Korean isolate).
AB  - Red pepper, one of the most important vegetable crops in Korea, is severely
      affected by viral diseases causing 20-50% reduction in product yield. A pepper
      strain of tobacco mosaic virus (TMV-p) is the most common virus in red pepper. To
      study the molecular structure of the TMV-p virus, we generated cDNA clones of the
      viral genome. Partial sequencing of a few cDNA clones revealed that TMV-p shares
      a 98% identity at the nucleotide level with the Spanish isolate of pepper mild
      mottle virus (PMMV-s). This suggests that TMV-p should be reclassified as the
      Korean isolate of PMMV (PMMV-k). The coat protein (CP) gene together with the 3'
      untranslated region of the PMMV-k virus was obtained by reverse transcriptase
      polymerase chain reaction (RT-PCR) using oligomers deduced from the sequence of
      PMMV-s. The sequence analysis of the CP gene and the 3' untranslated region
      further confirmed that PMMV-k is highly related to PMMV-s. The CP gene and the 3'
      untranslated region of PMMV-k were cloned into a plant expression vector and the
      construct was introduced into tobacco plants. The transgenic plants expressing
      the PMMV-k CP gene were delayed in developing systemic disease or failed to
      develop symptoms at all after inoculation with PMMV-k. Delay of symptoms was also
      observed when the plants were inoculated with TMV-OM which shares a 74% homology
      with PMMV-k in the amino acid sequence of the CP region. In a local lesion host,
      the CP expressing plants exhibited a greatly reduced number of necrotic lesions
      as compared to control plants after inoculation with TMV-OM. Our results show
      that CP-mediated viral resistance is readily applicable in the case of PMMV-k and
      can provide resistance to other viruses in the tobamovirus group.

PMID- 9264017
TI  - Expression of brain-derived neurotrophic factor mRNA stimulated by basic
      fibroblast growth factor and platelet-derived growth factor in rat hippocampal
      cell line.
AB  - Brain-derived neurotrophic factor (BDNF) promotes neuronal cell survival and
      differentiation in the central nervous system. BDNF mRNA is expressed at high
      levels in hippocampus and BDNF serves as a trophic factor in primary cultures of
      rat hippocampus. A hippocampal stem cell line HIB5, which is immortalized by the
      temperature sensitive SV 40 T antigen, undergoes neuronal differentiation at non
      permissive temperatures. During the differentiation process, platelet-derived
      growth factor (PDGF) and basic fibroblast growth factor (bFGF) facilitate cell
      survival and differentiation in HiB5 cells as well as in primary cultures of rat
      embryonic hippocampal cells. This report demonstrates that HiB5 cells express a
      functionally active PDGF beta receptor and that PDGF and bFGF stimulate the
      expression of BDNF within 2 h. These results propose that BDNF is a candidate
      mediator of trophic effects of PDGF and bFGF in the hippocampal stem cell line
      HiB5.

PMID- 9264018
TI  - Ribozyme mediated targeting of cucumber mosaic virus RNA 1 and 2 in transgenic
      tobacco plants.
AB  - Hammerhead ribozymes have been extensively used to inhibit the expression of
      cellular genes or viral genes mainly in the animal study. In this study, we
      designed a ribozyme targeting the conserved leader sequences of cucumber mosaic
      virus (CMV) RNA 1 and 2. The ribozyme, with asymmetric lengths of flanking
      complementary regions, cleaved a model substrate RNA efficiently at 26 degrees C
      as well as at 37 degrees C or 50 degrees C in vitro. And the ribozyme encoding
      sequence was introduced into tobacco plants and expressed with the CaMV 35S
      promoter and 3' NOS terminator in a monomeric type (pBIR1), tandemly repeated
      type (pBIR3), and cotranscriptionally combined type (pRokR) with 2.2 copies of
      I17N satellite RNA. Virus challenging experiments in F1 plants of respective
      transformants with CMV-Y showed specific reductions of viral RNA 1 and 2 in
      comparison with RNA 3 or 4. Although young plants of a three-leaf-stage showed
      rather similar mild symptom attenuations in all constructions compared to CMV-Y
      inoculated wild type, fully grown plants showed a differential degree of
      resistance upon systemic infections of CMV-Y in pRokR, pBIR3 and pBIR1
      transformed plants in a decreasing order.

PMID- 9264019
TI  - Cloning of a cysteine proteinase cDNA of adult Paragonimus westermani by
      polymerase chain reaction.
AB  - Cysteine proteinase cDNA fragment from adult mammalian trematode, Paragonimus
      westermani was amplified by reverse transcription-polymerase chain reaction (RT
      PCR) using degenerate oligonucleotide primers derived from conserved cysteine
      proteinase sequences. The 5' and the 3' regions of the cysteine proteinase gene
      were amplified using the PCR protocol for the rapid amplification of cDNA ends
      (RACE). It has an open reading frame of 804 bp. The deduced amino acid sequence
      consists of 268 amino acids. Sequence analysis and alignment showed significant
      sequence similarity to other eukaryotic cysteine proteinases and conservation of
      the cysteine, histidine, and asparagine residues that form the catalytic triad.
      The cysteine proteinase cDNA fragment was also subcloned in the expression vector
      pET and expressed as a C-terminal His-tag fusion protein in Escherichia coli.

PMID- 9264020
TI  - Evaluation of the N-terminal role in peptide antigenicity of the preS2 region of
      the hepatitis B virus surface antigen.
AB  - Previously we reported that the N-terminal sequence 120-129 of the preS2 region
      of the hepatitis B virus (HBV) surface antigen (HBsAg) plays an important role in
      peptide antigenicity against an preS2 specific anti-HBsAg monoclonal antibody (H8
      mAb) by affecting the B cell epitope conformation of a peptide existing within
      the sequence 130-145. In this study, we tried to confirm the previous results
      using a series of N-terminal sequentially deleted peptides and peptides
      substituted at position 127. This position was previously found to be important
      for H8 mAb binding. Peptide antigenicity of sequentially deleted peptides was
      gradually decreased when the residues from 125 to 129 were deleted, indicating
      that the residues cumulatively affect antigenicity. Peptide antigenicity relative
      to the substituted residues at position 127 of p123 showed an order of F > I > E
      > or = T > A > or = P > K and was correlated with their CD spectra. Structure
      dependent peptide antigenicity was also found in many polyclonal antisera
      produced by immunization with peptide-protein conjugates and HBsAg. Twenty-nine
      out of 34 polyclonal antisera had reactivities increased 2-fold or more with p123
      relative to those with p130. Among them, 10 antisera showed increased
      reactivities of 7 fold or more. These results confirm our previous results, which
      suggested the existence of the conformational B cell epitope in the preS2 region
      maintained by the N-terminal sequence. This experimental also suggests that N
      terminal sequence 125-129 is important in maintaining a higher antigenic
      structure.

PMID- 9264021
TI  - Evidence for the complex formation between reverse transcriptase and multicopy
      single-stranded DNA in retron EC83.
AB  - Multicopy single-stranded DNA (msDNA) is produced by reverse transcriptase (RT)
      and is mutagenic in E. coli. In order to study the interaction between msDNA and
      RT, an RT open reading frame of retron EC83 was fused with maltose binding
      protein. The fusion protein, MBP-RT, was active in msDNA synthesis. The msDNA was
      copurified with MBP-RT by amylose affinity column. When purified msDNA was mixed
      with MBP-RT, the msDNA formed a complex with the fusion protein. These results
      show that msDNA is present as a complex with RT in vivo and it is able to form
      such a complex in vitro. We suggest that RT may compete with MutS protein for
      binding to msDNA and thereby controls mutagenesis by msDNA.

PMID- 9264022
TI  - Plastid development in disc cells of glandular trichomes of Cannabis
      (Cannabaceae).
AB  - Plastids in lipophilic glandular trichomes of chemically fixed (CF) and high
      pressure cryofixed-cryosubstituted (HPC-CS) bracteal tissues of Cannabis were
      examined by transmission electron microscopy. In CF preparations, plastids in
      disc cells prior to secretory cavity formation possessed several lobed and
      dilated thylakoid-like features. In glands with secretory cavities, thylakoid
      like features aggregated to form reticulate bodies that distended regions of the
      elongated plastids. Electron-gray inclusions evident on the plastid surface
      appeared continuous with the reticulate body. Inclusions of similar electron
      density also appeared in the cell cytoplasm, along the plasma membrane, between
      the plasma membrane and cell wall facing the cavity, and in the secretory cavity
      in both CF and HPC-CS preparations. The bilayer structure of membranes of the
      plastid envelope was evident in HPC-CS but not in CF preparations. In HPC-CS
      preparations, secretions were evident on the plastid surface and were continuous
      with those in the plastid through pores in the envelope. This study supports an
      interpretation that these specialized plastids, lipoplasts, synthesize secretions
      that are transported through the plasma membrane and cell wall to subsequently
      accumulate in the secretory cavity.

PMID- 9264023
TI  - Cyclins and cyclin dependent kinases during cardiac development.
AB  - The molecular mechanisms that regulate the cardiomyocyte cell cycle and its
      terminal differentiation remain largely unknown. To determine which cyclins or
      cyclin dependent kinases (CDKs) are important for cardiomyocyte proliferation, we
      examined the expression of cyclins and CDKs during normal cardiac development.
      All cyclins and CDKs were highly expressed during embryonic cardiac development,
      then they decreased at different rates after birth. The mRNAs and proteins of
      cyclins A and B (G2 and M phase cyclins) were found in embryonic and neonatal
      hearts, but were not detected in young or adult hearts. In contrast, while the
      mRNAs of cyclins D1, D2, D3, and E (G1 and S phase cyclins) were observed during
      all stages of development, the proteins of cyclins D1, D3, and E were observed in
      hearts at the young growth stage, although the levels decreased differently.
      Reverse transcriptase-polymerase chain reaction (RT-PCR) using specific cyclin B
      and D3 primers revealed that cyclins B and D3 originated from cardiomyocytes and
      noncardiomyocytes. The CDKs (cdc2, CDK2, and CDK4) were highly expressed during
      embryonic cardiac development and maintained almost constant levels during
      neonatal periods. However, they were expressed at very low levels at the young
      and adult stages. The pattern of proliferating cell nuclear antigen (PCNA)
      expression during cardiac development was similar to the expression of CDKs.
      These findings suggest that all cyclins and CDKs are involved in the cardiac cell
      cycle, and that marked and rapid reduction of mitotic cyclins may be associated
      with the withdrawal of the cardiac cell cycle after birth.

PMID- 9264024
TI  - Cloning and expression of a gene encoding Moraxella sp. CK-1 autolysin.
AB  - A gene of Moraxella sp. CK-1 encoding cell wall lytic activity has been cloned
      and expressed in E. coli. A genomic library of Moraxella sp. CK-1 was constructed
      in the multifunctional phagemid vector pT7T3 19u, with partial Sau3A digests of
      Moraxella sp. CK-1 genomic DNA inserted at the BamHI restriction site. Screening
      of about 5,000 transformants for cell lysis activity in LB agar plates containing
      Micrococcus Iuteus cells gave one positive clone harboring the 3.7 kb insert
      (pMXA282). Restriction mapping and deletion analysis of the recombinant plasmid
      carrying a 3.7 kb insert suggested that the autolysin gene was located within a
      1.1 kb BamHI-PstI fragment. Analysis of extracts of E. coli clone harboring
      recombinant plasmids on renaturing SDS-polyacrylamide gels containing heat-killed
      Micrococcus luteus cells showed a clear zone around a polypeptide of about 32
      kDa. Lytic activity against Micrococcus luteus cell walls by the cloned autolysin
      was maximum at pH 9.0. Even in conditions of over pH 10.0, this cloned autolysin
      showed a vigrous lytic activity. Southern blot analysis suggested the existence
      of other homologous regions in Moraxella sp. CK-1 genome.

PMID- 9264025
TI  - Analysis of the structure and expression fo the TFIIB gene in Drosophila
      melanogaster.
AB  - We have isolated and characterized a genomic clone encoding the Drosophila
      melanogaster transcription factor IIB (TFIIB). The coding region of the TFIIB
      gene is interrupted by three short introns. The 5'-flanking region of the gene
      lacks the typical TATA box sequence like those of other known genes encoding the
      general transcription factors. In addition, the 5'-flanking region of the gene
      contains several common DNA sequences present in Drosophila TBP and TFIIS genes,
      suggesting the common regulation mechanism of gene expression. RNA blot analysis
      revealed that the gene expresses 1.6 kb, 1.3 kb and 1.2 kb mRNAs throughout
      development and in adults. Deletion analysis of the promoter region shows that
      the minimal promoter necessary for efficient expression is located between -698
      (PstI) and +60 relative to the transcription start point. Within this minimal
      promoter region, the upstream regulatory element responsible for the stimulation
      of gene expression may exist in the DNA fragment between -698 (PsfI) and -351
      (StuI).

PMID- 9264026
TI  - Purification and some properties of ribulose 1,5-bisphosphate
      carboxylases/oxygenases from Acinetobacter sp. strain JC1 and Hydrogenophaga
      pseudoflava.
AB  - Ribulose 1,5-bisphosphate carboxylases/oxygenases (RuBisCOs) of two
      carboxydobacteria, Acinetobacter sp. strain JC1 and Hydrogenophaga pseudoflava,
      grown on carbon monoxide were purified and partially characterized. RuBisCO of
      Acinetobacter sp. JC1 was purified 5-fold in eight steps to homogeneity, with a
      yield of 1.6%. The final specific activity of the purified enzyme was 39.5 nmol
      CO2 incorporated per min per mg protein. The molecular weight of the native
      enzyme was determined to be 520,000. Sodium dodecyl sulfate-gel electrophoresis
      revealed two nonidentical subunits of molecular weights 53,500 and 15,000. The Km
      and Vmax for CO2 were 36.7 microM and 296.1 nmol per min per mg protein,
      respectively, and those for ribulose 1,5-bisphosphate were 3.7 microM and 770
      nmol per min per mg protein, respectively. The enzyme of H. pseudoflava was
      purified 55-fold in eight steps to homogeneity, with a yield of 3.6%. The final
      specific activity was 304.3 nmol CO2 incorporated per min per mg protein. The
      molecular weight of the enzyme was estimated to be 505,000. The enzyme was found
      to have two kinds of nonidentical subunits of molecular weights 51,500 and
      14,000. The Km and Vmax for CO2 were found to be 16.4 microM and 777.8 nmol per
      min per mg protein, respectively, and those for ribulose 1,5-bisphosphate were
      0.1 microM and 436.2 nmol per min per mg protein, respectively. The N-terminal
      amino acid sequences of the large and small subunits of Acinetobacter sp. JC1
      enzyme were Ala-Asp-Arg-Trp-Asn-Ala-Gly-Val-IIe-Pro-Tyr-Ala-Glu-Met-Gly and Met
      Arg-Ile-Thr-Glu-Gly-Thr-Phe-Ser-Tyr-Leu-Pro-Asp-Phe-Thr, respectively. The
      sequences of the H. pseudoflava enzyme were Ala-Thr-Lys-Thr-Tyr-Asu-Ala-Gly-Val
      Lys-Glu-Tyr-Trp-Ser-Thr and Met-Ser-Met-Gln-Asp-Tyr-His-Ser-Arg-Leu-Ser-Asp-Pro
      Ala-Ile, respectively. The peptide map of RuBisCO from Acinetobacter sp. JC1
      grown on carbon monoxide was different from that of the bacterium grown on
      methanol. The two RuBisCOs, however, were found to be identical in N-terminal
      residue and antigenic property. The RuBisCO of Acinetobacter sp. JC1 was found to
      share no immunological properties with those of H. pseudoflava, Oligotropha
      carboxidovorans and Pseudomonas carboxydohydrogena.

PMID- 9264027
TI  - Temperature sensitivity of a class I tRNA synthetase induced by artificial
      breakage of polypeptide chain.
AB  - Escherichia coli methionyl-tRNA synthetase consists of catalytic, anticodon
      binding, and dimerization domains. The polypeptide was genetically cleaved and
      expressed as multiple subunits to investigate how peptide breakage affects the
      activity and stability of the enzyme. Mutants cleaved near conserved or
      functionally important sites were inactive. A few bipartite mutants were active,
      but they showed temperature sensitivity in their activity and stability. An
      additional cleavage of the active bipartites inactivated the enzyme, suggesting
      that at least two functional domains have to be covalently connected to retain
      the activity. This approach proves to be useful in determining the structural and
      functional organization of a protein.

PMID- 9264028
TI  - Monitoring catecholamine differentiation in the embryonic brain and peripheral
      neurons using E. coli lacZ as a reporter gene.
AB  - An X-gal based histochemical assay was used to detect catecholamine (CA) cells in
      transgenic mouse embryos, in which the expression of the lacZ reporter was driven
      by the tissue-specific promoter of the rat tyrosine hydroxylase (TH) gene. As the
      first enzyme in the biosynthetic pathway for CA neurotransmitters, TH is a
      specific phenotypic marker for CA cells in the central and peripheral nervous
      systems of adult animals. During embryogenesis, TH expression appears permanently
      within CA-producing cells, and transiently within several other cell types. In
      this study we were able to monitor TH expression in transgenic mouse embryos by
      following the expression of the lacZ reporter in substantia nigral dopaminergic
      neurons in the central nervous system, the trigeminal (V) sensory ganglia, and
      dorsal root ganglia in the periphery. Our results demonstrate that the rat TH
      promoter-lacZ transgene provides an important experimental tool for monitoring
      catecholaminergic lineage cells during embryogenesis.

PMID- 9264029
TI  - Partial anatomical and physiological characterization and dissociated cell
      culture of the nervous system of the marine mollusc Aplysia kurodai.
AB  - Snail nervous systems are powerful tools for neurobiological studies as the
      biophysical properties of the giant neurons and their neural circuits can be
      examined in relation to specific behaviors of animals. The marine mollusc Aplysia
      californica is particularly useful for analyzing the components of learning and
      memory at the molecular and cellular levels. Here we partially examined the
      nervous systems of two species (A. kurodai and A. juliana) commonly found along
      the Korean coast in comparison with that of A. californica, one of the American
      marine snails. A. kurodai appeared to be identical to A. californica in both
      anatomical and physiological properties of the nervous system. A. juliana could
      be distinguished from A. californica in certain morphological aspects of the
      nervous system. The hemolymph either from A. kurodai or from A. juliana was
      required for effectively elongating neurite outgrowth of A. kurodai neurons in
      dissociated cell culture. The cultured cells retained neuronal properties such as
      neurite outgrowth, synapse formation, and generation of action potentials. The
      sensory cells of A. kurodai in dissociated cultures showed a response to
      serotonin (5-HT) of spike broadening and enhanced membrane excitability as in
      intact ganglia. Therefore, the nervous system and dissociated neuronal culture of
      A. kurodai may be useful for studying learning and memory in the context-of well
      defined neural circuits of A. californica.

PMID- 9264030
TI  - Purification and antifungal activity of a basic 34 kDa beta-1,3-glucanase from
      soybean hypocotyls inoculated with Phytophthora sojae f. sp. glycines.
AB  - Inoculation of soybean (Glycine max L. cv. Jangyup) hypocotyls with Phytophthora
      sojae f. sp. glycines results in a marked accumulation of some pathogenesis
      related (PR) proteins. A basic beta-1,3-glucanase (34 kDa) was purified from
      soybean hypocotyls infected by an incompatible race of P. sojae f. sp. glycines
      using CM-cellulose cation exchange chromatography and Bio-gel P-60 gel
      filtration. The purified soybean beta-1,3-glucanase cross-reacted with polyclonal
      antibody raised against a tomato beta-1,3-glucanase. The activity of beta-1,3
      glucanase was much higher in the infected soybean hypocotyls than the healthy
      ones. The beta-1, 3-glucanase purified from soybean inhibited spore germination
      and hyphal growth of the chitin-negative fungus P. sojae f. sp. glycines, but did
      not show any antifungal activity against the chitin-containing fungi Alternaria
      mali, Colletotrichum gloeosporioides, and Magnaporthe grisea.

PMID- 9264031
TI  - Genomic organization of the human DDX13 gene located between RD and RP1 in the
      class III MHC complex.
AB  - Recently we cloned a novel human cDNA homologous to yeast SKI2, reported a
      partial cDNA sequence, and mapped the gene to human chromosome 6p21 (Lee et al.,
      1995). It was a member of the DEAD/DExH family gene with seven conserved helicase
      domains; thus, it was named DDX13 consequently. We determined the complete
      genomic organization of the DDX13 gene. It consisted of 28 exons distributed over
      11 kb of genomic DNA. An Alu element was present in introns 17 and 18,
      respectively. The major transcription start site was located 390 bp upstream from
      the translation initiation codon. The DDX13 gene was located in the class III
      region of the MHC between the genes coding for two other nuclear proteins, RD and
      RP1. The RD and DDX13 genes were oppositely oriented, and their first exons were
      overlapped. The distance between their first methionine codons was only 745 bp.
      It was of note that DDX13 and RD are in such proximity that their 5' regulatory
      regions overlap. The RP1 gene was located immediately downstream from the DDX13
      gene in the same transcriptional orientation, and the distance between the stop
      codon of DDX13 and the translation initiation codon of RP1 was 2,272 bp.

PMID- 9264032
TI  - Improvement of the 3'-5' exonuclease activity of Taq DNA polymerase by protein
      engineering in the active site.
AB  - Taq DNA polymerase from Thermus aquaticus has been shown to be very useful in the
      polymerase chain reaction method. Taq DNA polymerase has a domain at its amino
      terminus (residue 1 to 291) that has a 5'-3' exonuclease activity, a 3'-5'
      exonuclease domain in the middle (residue 292 to 423), and a domain at its C
      terminus that catalyzes polymerase reactions. Taq DNA polymerase is classified
      into the polI family which is represented by E. coli DNA polymerase I. The three
      dimensional structural alignment of 3'-5' exonuclease domains from the polI
      family, DNA polymerases leads us to understand why Taq DNA polymerase does not
      carry out proof-reading in the polymerase chain reaction. Three sequence motifs,
      called ExoI, II, and III must be present in order to carry out proof-reading by
      the 3'-5' exonuclease reaction in DNA polymerization, but Taq DNA polymerase
      contains none of them. The key catalytic module in the 3'-5' exonuclease is two
      metal ions chelated by active-site carboxylic amino acids. In order to render the
      3'-5' exonuclease activity in Taq DNA polymerase, a catalytic module was
      constructured in the active site by protein engineering. The mutant Taq DNA
      polymerase shows twice as much the 3'-5' exonuclease activity as that of wild
      type DNA polymerase.

PMID- 9264034
TI  - Colchicine activates actin polymerization by microtubule depolymerization.
AB  - Swiss 3T3 fibroblasts were treated with the microtubule-disrupting agent
      colchicine to study any interaction between microtubule dynamics and actin
      polymerization. Colchicine increased the amount of filamentous actin (F-actin),
      in a dose- and time-dependent manner with a significant increase at 1 h by about
      130% over control level. Confocal microscopic observation showed that colchicine
      increased F-actin contents by stress fiber formation without inducing membrane
      ruffling. Colchicine did not activate phospholipase C and phospholipase D,
      whereas lysophosphatidic acid did, indicating that colchicine may have a
      different mechanism of actin polymerization regulation from LPA. A variety of
      microtubule-disrupting agents stimulated actin polymerization in Swiss 3T3 and
      Rat-2 fibroblasts as did colchicine, but the microtubule-stabilizing agent taxol
      inhibited actin polymerization induced by the above microtubule-disrupting
      agents. In addition, colchicine-induced actin polymerization was blocked by two
      protein phosphatase inhibitors, okadaic acid and calyculin A. These results
      suggest that microtubule depolymerization activates stress fiber formation by
      serine/threonine dephosphorylation in fibroblasts.

PMID- 9264033
TI  - Endogenous glutamate levels regulate nerve growth factor mRNA expression in the
      rat dentate gyrus.
AB  - The levels of nerve growth factor (NGF) mRNA can be regulated in vitro and in
      vivo in the hippocampal formation by events associated with pharmacological
      activation of glutamate receptors. In the present study, the level of NGF mRNA in
      the hippocampal formation was examined following an intrahippocampal injection of
      1 nmole fluorocitrate, which temporarily inhibits the astrocyte metabolic
      activity in vivo. Consistent with previous findings, fluorocitrate treatment
      significantly increased glutamate levels and decreased glutamine levels in the
      dentate gyrus as determined by in vivo microdialysis. The increased ratio of
      glutamate to glutamine was followed by a significant increase in NGF mRNA
      expression selectively in dentate gyrus granule cells. The effects of increasing
      glutamate levels were blocked by pretreatment with 50 nmole 2-amino-5
      phosphonovalerate (AP5), a competitive antagonist that acts at the N-methyl-D
      aspartate (NMDA) glutamate receptor subtype. These findings suggest that NGF mRNA
      expression is regulated, in part, by changes in endogenous glutamate levels,
      partially through enhanced excitatory neurotransmission through NMDA receptors.

PMID- 9264035
TI  - Insulin activates Ras in the PC12 cell line.
AB  - To address whether Ras can be activated by insulin in the PC12 cell line,
      proteins interacting with insulin receptor and IRS-1 molecules and their tyrosine
      phosphorylation were analyzed by immunoblotting following immunoprecipitation
      with antibodies. Tyrosine phosphorylation of the insulin receptor and IRS-1 was
      increased by insulin. Grb2 and Ras-GAP appeared in the immunoprecipitates by anti
      insulin receptor and anti-IRS-1 from insulin-treated cells. In addition, PI 3
      kinase was activated by insulin treatment in this cell line and Grb2, Ras-GAP,
      and MAP kinase were coprecipitated with Ras from both insulin-treated and NGF
      treated cells. Analysis of MAP kinases from insulin-treated cells revealed that
      insulin, like NGF, increased tyrosine phosphorylation. However, activation of the
      MAP kinase by NGF lasted longer than activation by insulin. These results
      indicate that Ras can be activated by insulin in the PC12 cell line and that Ras
      activation is neither an accurate nor a plausible method of discriminating
      signals between proliferation and differentiation.

PMID- 9264036
TI  - CRP:cAMP complex binding to the lac operator region induces a structural change
      in lac DNA.
AB  - Changes in DNA structure induced by cAMP receptor protein (CRP) binding to the
      lac-control region contained on a 231 bp fragment were investigated by
      measurement of the molar cyclization factor (jM). Increases in jM were observed
      at low to moderate CRP: cAMP complex concentrations and correlated with CRP
      binding to the promoter-proximal CRP binding site. At CRP:cAMP complex
      concentrations greater than 200 nM, decreases in jM correlated with CRP binding
      to both the promoter-proximal and the operator-proximal CRP binding sites. These
      results show that binding of the CRP:cAMP complex to the operator-proximal CRP
      binding site induces a structural change in lac DNA.

PMID- 9264037
TI  - In situ localization of WDNM1 and ferritin heavy chain gene expression in mammary
      gland.
AB  - In situ hybridization was performed with sections obtained from mammary gland at
      10 days of lactation and at 1 and 3 days of involution using either digoxigenin
      labeled antisense or sense RNA probe in order to localize expression of WDNM1 and
      ferritin heavy chain mRNA. The WDNM1 gene was predominantly expressed in the
      layer of secretory epithelial cells surrounding the lumen of mammary gland
      alveoli. The lower levels of WDNM1 mRNA were observed at involution day 3
      compared to involution day 1. The expression of ferritin heavy chain mRNA also
      appears to be confined to the epithelial layer of mammary alveoli. The lower
      levels of ferritin heavy chain mRNA were observed at involution day 3 compared to
      involution day 1.

PMID- 9264038
TI  - A pharmacological and clinical review on topiramate, a new antiepileptic drug.
AB  - Topiramate is a new antiepileptic drug which has recently become available in the
      United States and in a number of European countries. Pharmacological studies
      suggest that its mode of action is multifactorial and involves blockade of
      voltage-dependent sodium channels, potentiation of GABAergic transmission and
      inhibition of excitatory pathways through an action at AMPA receptor sites.
      Carbonic anhydrase inhibiting properties have also been demonstrated but they are
      considered not to be relevant to anticonvulsant activity. Topiramate is well
      absorbed from the gastrointestinal tract, peak plasma levels being usually
      attained in 2-3 hours. The drug is negligibly (9-17%) bound to plasma proteins
      and is eliminated partly by renal excretion in unchanged form and partly by
      oxidation and hydrolysis. In healthy volunteers, the half-life is about 20-30
      hours, but elimination rate is accelerated in patients taking concomitant enzyme
      inducing drugs such as phenytoin, carbamazepine and barbiturates. Topiramate has
      no major effects on plasma levels of concurrent anticonvulsants, except for a
      rise in plasma phenytoin in occasional patients. In double-blind add-on trials in
      refractory partial epilepsy, a significant reduction in seizure frequency has
      been demonstrated in over 40% of topiramate-treated patients (vs about 10% of
      those treated with placebo), a response rate which compares favourably with that
      observed with other new antiepileptic drugs. Dosages found to be effective in add
      on controlled trials range between 200 and 1000 mg day-1, although most patients
      are likely to benefit from receiving 400 mg day-1 or less. Preliminary data
      suggest that topiramate may be effective also in generalized epilepsies, but this
      needs to be confirmed in prospective studies. The most common adverse effects of
      topiramate are CNS-related and include dizziness, fatigue, visual disturbances,
      ataxia, mental slowing and impaired concentration. Paresthesias, anorexia, weight
      loss and increased risk of nephrolithiasis have been also reported. Many of these
      effects are related to dose and/or to rate of dose titration. Based on these
      data, topiramate appears to be a valuable new drug, whose main current indication
      is in the add-on management of refractory partial and secondarily generalized
      seizures. Studies on its potential-value as monotherapy are in progress.

PMID- 9264040
TI  - PI3K signal and DNA repair: a short commentary.
AB  - PI3K was originally discovered as a lipid kinase involved in the phosphorylation
      of the inositol ring in position -3, leading to the synthesis of phosphatidyl
      inositol-3-4 bisphosphate. The enzyme purified from rat liver is an heterodimer
      of two subunits of 85 and 110 KD respectively: it phosphorylates the D3 hydroxyl
      of phosphoinositides to produce phosphatidyl-inositol-3-phosphate. So far the
      function of the 3-phospho-inositide is unclear. It is likely that the entire
      phospholipid serves as a second messenger, since no phospholipase C has yet been
      found that can cleave the inositol group with a 3 phosphate residue. However the
      activation targets of this second messenger are still poorly known. Recently a
      novel/serine/theronine kinase was insolated by three groups and called
      differently RAC, PKB and AKT. It exhibits sequence homology with protein kinase A
      and C at the carboxyl terminal, whereas the aminoterminal domain has a plectrin
      homology. Activation of ATK is inhibited by wortmannin, a specific inhibitor of
      PI3K at very low concentrations. Furthermore inositol-3-phosphate can activate
      ATK in vitro. In addition very recently, a linkage of G-protein coupled receptors
      to the MAP kinase signalled pattern through PI3K has been discovered. But what is
      downstream of this pathway? 70S6 kinase is an attractive candidate since this
      kinase, involved in protein synthesis, is activated by AKT in vivo. Interestingly
      AKT is the cellular protooncogene of v-ATK and this implies that ATK induces a
      pathway of oncogenic transformation. AKT is inhibited by dominant negative
      mutants of ras and thus involved in the ras-raf-MAP kinase pathway. The role of
      PI3K is still indefinite but it must have a paramount importance in cell
      signalling since nearly all growth factor receptors recruit this enzyme and that
      the activity of fundamental growth factor receptors like PDGF, EGF and insulin
      are blocked by the specific inhibitor wortmannin, leading to the conclusion that
      the PI3K signal is much important in mitogenesis, protein synthesis, membrane
      ruffling, cell transformation and cell cycle progression.

PMID- 9264039
TI  - Complex interplay among apoptosis factors: RB, p53, E2F, TGF-beta, cell cycle
      inhibitors and the bcl2 gene family.
AB  - Apoptosis is a fundamental cell program as important as growth, differentiation
      and quiescence. It regulates tissue development, homeostasis and it is a basic
      defence against cancer. The cell can undertake multiple apoptotic pathways, where
      different elements are involved. In this report, we would like to stress
      particularly that the p53/RB pathway and its complex, interplay with the bcl2
      gene family, where paramount elements of apoptosis regulation are operating. It
      is generally believed that bcl2 blocks apoptosis at the level of the activation
      of ICE-(Interleukin Converting Enzymes)-like proteases [1,2]. The interconnection
      between apoptosis and cell cycle is very important and complex and we will start
      the story from this very up-to-date point of view.

PMID- 9264041
TI  - Immunopharmacological activity of aporphinoid alkaloid oxoglaucine.
AB  - The ability of aporphinoid alkaloid oxoglaucine to influence T- and B-cell immune
      response was studied in mice models. The substance inhibited in vitro mitogen
      induced lymphocyte proliferation and suppressed antibody response to sheep red
      blood cells (SRBC) and lipopolysaccharide (LPS) in vivo effectively. The action
      depended on the relative timing of antigen and oxoglaucine administration. The
      substance manifested stimulatory effect in popliteal lymph node (PLN) reaction
      and LPS-induced B-cell activation. In the chronic inflammatory model of adjuvant
      arthritis oxoglaucine exhibited stimulatory or suppressive action related to the
      kinetics of the process. At low doses (1 or 2 mg kg-1) oxoglaucine improved the
      outcome of Klebsiella pneumoniae infection, while at higher doses (10 or 20 mg kg
      1) the substance caused an impairment of host resistance to infectious agent. The
      comparison with cyclophosphamide in some tests showed that oxoglaucine was
      effective in manifold lower doses. In conclusion, oxoglaucine exerted
      immunomodulatory effects in vivo in a dose-dependent and protocol-dependent
      manner. Yet, its overall action might be attributed to the different sensitivity
      of the cells involved in the developing immune response.

PMID- 9264042
TI  - Liver injury model induced in mice by a cellular immunologic mechanism--study for
      use in immunopharmacological evaluations.
AB  - Various drugs for clinical hepatitis were applied to a new model of liver injury
      induced in mice by delayed-type hypersensitivity to picryl chloride (PCI-DTH).
      The hepatoprotective agent, biphenyl dimethyl dicarboxylate showed a remarkable
      improvement against the elevation of serum transaminase levels as well as the
      histopathological changes when given during the induction phase but not during
      the effector phase of DTH reaction. Cyclophosphamide (Cy), an immunosuppressive
      agent, significantly inhibited the enzymatic elevation given in both induction
      and effector phases. However, Cy did not affect the sustaining of liver injury 4
      weeks after the liver injury eliciting. Moreover, the consecutive administration
      of prednisolone (Pred), in both induction phase and sustaining process of liver
      injury, conversely caused a more severe liver damage. Such exacerbation by Pred
      might be resulted from its toxic action to hepatocytes. As an immunomodulatory
      and antiinflammatory agent, glycyrrhizin remarkably improved the sustaining
      process but not the acute phase of the liver injury. Krestin and malotilate also
      showed an improving effect on the sustaining development of liver injury. These
      findings that most of above drugs showed an improving action in their respective
      manner suggest that this model may be useful for the pharmacological evaluation
      of drugs especially immunomodulating agents for hepatitis.

PMID- 9264043
TI  - Bisaramil and antiarrhythmics as inhibitors of free radical generation.
AB  - The aim of this study was to investigate the effect of bisaramil--an
      antiarrhythmic drug under clinical trials-on free radical generation of isolated
      polymorph neutrophil granulocytes (PMN) and furthermore to compare its activity
      to that of well-known antiarrhythmics which have different modes of action. PMNs
      were isolated from healthy beagle dogs, and superoxide radical generation was
      induced by phorbol-myristate-acetate. Stimulated free radical generation capacity
      of PMNs and the time lag necessary for the initiation of free radical production
      were measured. All compounds were used at the concentrations of 10, 25, 50, 75,
      100 micrograms ml-1. None of the antiarrhythmics stimulated by itself the free
      radical generation. Bisaramil exerted concentration dependent inhibitory effect
      on PMA-stimulated free radical generation and prolonged the time lag
      concentration dependently. At the investigated concentration range of
      antiarrhythmics only propafenon, mexiletine and diltiazem showed similar activity
      to bisaramil, but clear concentration dependency could not be seen in any of the
      cases. According to the results of this study inhibition of the stimulated free
      radical production of isolated PMNs cannot be closely connected merely to either
      membrane stabilizing or Ca-antagonistic activity of drugs. In vitro and earlier
      measured in vivo inhibitory action of bisaramil on free radical generation
      indicate a possible cardioprotective effect existing independently from its
      antiarrhythmic one. This observation may be important in outlining of the
      clinical indication field of bisaramil, and may be useful in the treatment of
      reperfusional damage.

PMID- 9264044
TI  - Clonidine-induced emesis: a multitransmitter pathway concept.
AB  - The emetic effect of clonidine injected into the cerebral ventricles through
      chronically implanted cannulae was investigated in unanaesthetized cats.
      Clonidine (0.1-300 micrograms) induced dose-dependent and shortlasting emesis.
      The emesis induced by the supramaximal dose of clonidine (100 micrograms) was not
      abolished after the ablation of area postrema. Both the alpha 2 adrenoceptor
      blocking agent idazoxan and the mixed alpha 1 and alpha 2 adrenoceptor antagonist
      phenoxybenzamine, injected intracerebroventricularly, attenuated or abolished the
      emesis induced by clonidine (100 micrograms). On the other hand, the alpha 2
      adrenoceptor blocking agent yohimbine, the alpha 1 adrenoceptor blocking drug
      prazosin and the non-selective beta-adrenoceptor antagonist propranolol, injected
      into the cerebral ventricles, had no significant effect on clonidine-induced
      emesis. The antimuscarinic drug atropine injected into the cerebral ventricles
      prevented the clonidine-induced emesis in a dose-dependent manner. The dopamine
      antagonist chlorpromazine, the 5-hydroxytryptamine blocking agent methysergide
      and the histamine H1 and H2 receptor antagonists, antazoline and cimetidine,
      injected intracerebroventricularly reduced or abolished the emesis produced by
      clonidine. The ganglionic blocking substance mecamylamine and the opioid
      antagonist naloxone, all injected into the cerebral ventricles, had no
      significant effect on clonidine-induced emesis. In cats pretreated with the
      intracerebroventricular competitive inhibitor of the synthesis of catecholamines,
      alpha-methyl-p-tyrosine, as well as with the inhibitor of acetylcholine synthesis
      hemicholinium-3, the emesis caused by clonidine was depressed or abolished. The
      clonidine-induced emesis was also abolished when catecholamine stores were
      depleted by intracerebroventricular reserpine. However, the clonidine-induced
      emesis was not significantly changed when 5-hydroxylryptaminergic nerve terminals
      were damaged by 5,6-dihydroxytryptamine. It follows, therefore, that cholinergic
      and noradrenergic mechanisms are of basic importance for the emetic action of
      clonidine. With regard to receptors, the emesis induced by clonidine injected
      into the cerebral ventricles, is mediated at least in part through alpha
      adrenoceptors, muscarinic cholinoceptors, 5-hydroxytryptamine receptors and H1
      and H2 histamine receptors. These receptors appear to be located mostly
      presynaptically and they transmit emetic impulses to neurones integrating them
      into emesis. However, the direct effect of clonidine on postsynaptic receptors
      cannot be excluded, particularly when muscarinic and 5-hydroxytryptamine
      receptors are implicated. Taken together, these results point to the existence of
      a multitransmitter pathway/s outside the area postrema, subserving the central
      regulation of emesis.

PMID- 9264045
TI  - Effects of beta-blockers association with pilocarpine on rabbit intraocular
      pressure and heart rate.
AB  - The effect of 7-days BID (twice in a day) or TID (three times in a day)
      administration of the eye-drop combinations of timolol and pilocarpine (0.5% and
      2%, respectively), metipranolol and pilocarpine (0.1% and 2%, respectively) or
      placebo on intraocular pressure (IOP) and heart rate (HR) of conscious rabbits
      were studied in order to assess the pharmacological potency of the combinations
      and their heart side effects. TID administration of both pharmacological
      combinations was followed by similar decrease of IOP as measured over 24 h (at
      4.00 and 20.00 h). After the BID administration, a reduction in IOP was observed
      only twice with the timolol-pilocarpine combination. In contrast, a constant
      reduction in IOP was seen with the metipranolol-pilocarpine combination.
      Furthermore, the TID administration of the timolol-pilocarpine combination
      exerted a decrease of IOP that appeared to be more pronounced than that observed
      after the BID administration of the same combination, while no difference was
      found between the TID and BID administration of the metipranolol-pilocarpine
      treatment. Heart rate, when measured after 7 days of treatment, appeared to be
      constantly decreased only in the group of animals which received the TID
      administration of timolol-pilocarpine combination. The present results suggest
      that the BID or TID administration of metipranolol-pilocarpine combination was
      fully effective in reducing IOP without influencing HR. The timolol-pilocarpine
      association appeared to be fully active in reducing IOP only under the TID
      administration schedule. However, this rate of administration was followed by a
      constant reduction of HR. Thus, on a dose basis the metipranolol-pilocarpine
      combination appeared to be more effective in reducing IOP and less effective in
      inducing bradycardia than the timolol-pilocarpine association.

PMID- 9264047
TI  - Levodopa and 3-O-methyldopa in cerebrospinal fluid after levodopa-carbidopa
      association.
AB  - Since motor fluctuations in Parkinsonian patients might be, at least in part,
      explained by an antagonism between levodopa (LD) and its metabolite 3-O
      methyldopa (3-OMD) at blood-brain-barrier (BBB), we decided to study LD and 3-OMD
      plasma and cerebrospinal fluid (CSF) levels in subjects undergoing lumbar
      puncture for diagnostic purposes. After informed consent, 70 subjects took a
      tablet of carbidopa-levodopa association (Sinemet or Sinemet-CR) 0.5, 1, 2, 4, 8,
      12 h before blood and lumbar cerebrospinal fluid collection. LD and 3-OMD were
      determined by an HPLC-electrochemical method. The subjects treated with Sinemet
      CR had lower LD cerebrospinal fluid concentrations along with lower LD and higher
      3-OMD plasma concentrations. This pattern of LD cerebrospinal fluid
      concentrations may be explained by means of a transport competition between LD
      and 3-OMD at blood brain barrier level.

PMID- 9264048
TI  - Galantide improves social memory in rats.
AB  - The role of galanin in memory paradigms has been largely evaluated. The galanin
      antagonist galantide, a chimeric peptide obtained from amino acids 1-13 of
      galanin attached to the C-terminal fragment of bradykinin, has been found to
      improve social memory in 'social recognition' test when i.c.v. administered at
      doses varying from 6-6000 nmoles.

PMID- 9264046
TI  - A match between binding to beta-adrenoceptors and stimulation of adenylyl cyclase
      parameters of (-)isoproterenol and salbutamol on rat brain.
AB  - Inhibition experiments of (-)[3H]CGP 12177 binding by (-)isoproterenol and
      salbutamol were performed on synaptosomes prepared from rat brain cortex and
      cerebellum. Adenylyl cyclase (AC) stimulation experiments on slices of these
      structures were also performed, with measuring [14C]cAMP obtained from
      [14C]adenine. Studying beta 1- and beta 2-adrenoceptors (beta 2AR) separately,
      dissociation constants of (-)isoproterenol for the high- (KH) and low- (KL)
      affinity states are 8 and 206 nM, respectively, for beta 1AR, vs 20 and 900 nM
      for beta 2AR. With salbutamol, KH and KL for beta 2AR are 37 and 1250 nM,
      respectively, vs 430 and 8500 nM for beta 1AR. In any case, the proportion of
      high-affinity state (RH) of beta 2AR in the cerebellum (59% and 35% for (
      )isoproterenol and salbutamol, respectively) is twice that of beta 1AR (30% and
      18%). Surprisingly, the RH of cortex beta 2AR with (-)isoproterenol (30%) is
      significantly lower than in the cerebellum, but not with salbutamol (35%). To
      allow meaningful comparisons of potencies in stimulating [14C]cAMP production, we
      define the coupling efficiency (CE), applicable to specified beta AR subtype and
      agonist, and expressed as the maximal production of mol cAMP.mol-1 beta AR.min-1.
      The order of CE was always in favor of (-)isoproterenol vs salbutamol on
      cerebellum beta 2AR > on cortex beta 2AR > on cortex beta 1AR. This order
      indicates the partial agonism of salbutamol for both beta AR subtypes, and an
      intrinsic better coupling of beta 2AR vs beta 1AR in rat brain. Moreover, this
      order corresponds roughly to that of RH. Hence, CE is directly correlated with RH
      at least for these two agonists. EC50 for cAMP production for each subtype and
      agonist is in the same order than the respective KL, and might only reflect the
      rapid return of receptor to low-affinity state after the activation of Gs
      protein. In binding experiments on the whole beta AR in both areas, the pseudo
      Hill coefficient did not reach 1 with 0.3 mM guanosine 5'-(beta, gamma
      imido)triphosphate (GppNHp). This dysfunction of GppNHp in rat brain structures
      might be caused by a major difference in the regulation of coupling in the
      ternary complex as compared with peripheral tissues.

PMID- 9264049
TI  - LHRH receptors and LHRH receptor-bearing cells in pituitaries of streptozocin
      diabetic male rats.
AB  - Streptozocin (STZ)-diabetic rats have low hypothalamic luteotropic hormone
      releasing hormone (LHRH) secretion and various alterations of gonadotrope cells,
      among which low luteotropic hormone (LH) secretion. Possible causes for the
      gonadotrope disorders may be low hypothalamic LHRH secretion alone or combined
      with reduced (a) number of LHRH receptor sites, or (b) receptor to ligand
      affinity, or (c) of LHRH receptor-bearing cells. To clarify this question we
      determined by saturation and competition binding Bmax, KD and KA of the LHRH
      receptor sites and counted the receptor-bearing cells in pituitary glands of
      control and STZ-diabetic adult male rats. We found a single receptor class, the
      Bmax was strongly reduced in diabetic animals whereas both KD and KA were similar
      in the two groups. The number of LHRH receptor-bearing cells in diabetic animals
      was increased. Therefore a reduced number of receptor sites per gonadotrope cell
      occurs in our model. Since in the STZ-diabetic male rats the number of
      gonadotropes is increased, a higher number of receptor-bearing cells was
      observed. We conclude that the reduced LH secretion from the diabetic pituitary
      gland might be due to a reduced number of LHRH receptor sites in the pituitary
      gland. The increased number of receptor-bearing cells might partially compensate
      for this change.

PMID- 9264050
TI  - Gas chromatographic assay for estazolam in human plasma and results of a
      bioequivalence study.
AB  - This paper describes a new sensitive gas chromatographic method with electron
      capture detector to assay estazolam in human plasma, which has been developed and
      validated for pharmacokinetic purposes. The drug and the internal standard
      (triazolam) were extracted from plasma buffered at pH 9.0 into toluene and
      analysed on a widebore DB 17 column. The calibration curve covered the 1.0-200 ng
      ml-1 range with a mean determination coefficient of 0.9996. The quantification
      limit was 1.0 ng ml-1. This method was used to investigate the bioequivalence of
      a new formulation of estazolam in drops (test) and the formulation in tablets
      (reference, ESILGAN). Both formulations were administered at a single dose of 2
      mg in a clinical trial carried out on 24 healthy volunteers consisting of 12
      males and 12 females, following a crossover randomised design in two periods with
      wash-out. The test and the reference formulations proved to be fully
      bioequivalent according to operating guidelines, namely through 90% confidence
      intervals in the 0.80-1.25 range.

PMID- 9264051
TI  - Interaction between fluoxetine and haloperidol: pharmacokinetic and clinical
      implications.
AB  - The extent and clinical significance of the pharmacokinetic interaction between
      fluoxetine and haloperidol was studied in 13 schizophrenic patients with
      prominent negative symptoms. Patients stabilized on chronic low-dose haloperidol
      (3-8 mg day-1) received additional fluoxetine (20 mg day-1) for 12 consecutive
      weeks. Mean plasma concentrations of haloperidol increased significantly from 6.5
      +/- 2.4 nmol l-1 at baseline to 8.8 +/- 3.6 nmol l-1 (P < 0.01) at week 12 of
      fluoxetine treatment, but this effect was not associated with an increase in mean
      extrapyramidal side effects score on the Simpson and Angus Scale. The improvement
      in negative symptomatology, as measured by the Scale for Assessment of Negative
      Symptoms, did not correlate significantly with the increase in plasma haloperidol
      levels. Though our findings confirm that fluoxetine impairs haloperidol
      clearance, this interaction is unlikely to have adverse clinical consequences, at
      least in patients chronically stabilized on a low dosage of haloperidol. As
      fluoxetine is a potent inhibitor of cytochrome P450 (CYP) 2D6, these results also
      provide indirect evidence for an involvement of CYP2D6 in the metabolism of
      haloperidol.

PMID- 9264052
TI  - Association equilibrium of L-methamphetamine with serum albumin in various animal
      species.
AB  - The association equilibrium of complex formation between serum albumin (bovine,
      rat, rabbit, guinea pig, horse, mouse and chicken) and L-methamphetamine (MAMP)
      was determined by the use of ultrafiltration to examine the effect of animal
      species on adsorption of L-MAMP to albmin. Serum albumin L-MAMP complexes had the
      same Scatchard plot patterns in all species tested. The binding parameters of
      each association equilibrium were estimated by Rosenthal's method. One kind of
      binding site and non-specific binding sites were distinguished in terms of the
      association equilibrium between each serum albumin and L-MAMP in all species
      tested.

PMID- 9264053
TI  - A protective role for calcitonin gene-related peptide in water-immersion stress
      induced gastric ulcers in rats.
AB  - This study investigated the role of endogenous and exogenous calcitonin gene
      related peptide (CGRP) in water immersion stress (WIS)-induced gastric ulcers in
      rats. WIS produced gastric ulcers which were inversely correlated to the decrease
      in CGRP-like immunoreactivity observed in the whole thickness of the corpus
      stomach but not in its mucosal layers. Systemic administration of CGRP (100
      micrograms kg-1 s.c.) produced a significant decrease in lesion index of WIS
      ulcers and this protection was inhibited by functional ablation of afferent
      neurons induced by capsaicin pretreatment (100 mg kg-1 s.c. in two days, a week
      before the experiments). These findings suggest that sensory endogenous CGRP
      plays a defensive role in WIS-ulcers.

PMID- 9264054
TI  - 5-HT3 serotonin hetero-receptors inhibit [3H]acethylcholine release in rat
      cortical synaptosomes.
AB  - The present study was designed to verify the presynaptic localization of 5-HT3
      serotonin receptors on cholinergic, serotonergic and dopaminergic nerve endings
      in rat brain regions where they have been shown to modulate the release of these
      neurotransmitters. We measured the effect of 5-HT3 agonists on [3H]
      neurotransmitter release from superfused synaptosomes as a functional assay of
      the presence of 5-HT3 serotonin receptors. m-Cl-phenylbyguanide (m-Cl-PBG, 1
      microM) inhibited by 18% depolarization-evoked [3H]acethylcholine (ACh) release
      from cortical synaptosomes, and this effect was blocked by a potent and selective
      5-HT3 antagonist based on the arylpiperazine skeleton (VC 135, 0.03 microM).
      Ondansetron (0.1 microM) per se had an inhibitory effect as well, thus making it
      difficult to evaluate its interaction with m-Cl-PBG. Up to 10 microM, m-Cl-PBG
      did not affect [3H]dopamine release in striatum, nucleus accumbens and frontal
      cortex. A similar, although not significant inhibition (16%) of [3H]ACh release,
      was obtained with 2-methylserotonin (10 microM), which, at this concentration,
      did not modify either basal or depolarization-induced release of [3H]serotonin in
      hippocampus or [3H]dopamine in striatum. IN conclusion, our data suggest that 5
      HT3 hetero-receptors are located on cortical nerve endings where they directly
      inhibit acethylcholine release, but they do not seem to be located on
      serotonergic and dopaminergic nerve endings in the brain regions studied,
      probably having an indirect effect on these neurotransmitters release in rat
      brain.

PMID- 9264063
TI  - D1 and D2 dopamine and opiate receptors are involved in the restraint stress
      induced sensitization to the psychostimulant effects of amphetamine.
AB  - The time course of the restraint stress-induced sensitization to the stimulant
      effects of amphetamine (AMPH, 0.5 mg/kg IP) on locomotor activity was
      investigated for up to 8 days. In a series of separate experiments, the
      involvement of opioid and dopaminergic mechanisms in the development of acute
      restraint stress-induced behavioral sensitization were characterized. Both a
      single restraint session (2 h) and chronic restraint (2 h per day for 7 days)
      similarly potentiated the effects of AMPH on motor activity. This behavioral
      sensitization was prevented by the administration of naltrexone (2 mg/kg IP),
      haloperidol (1 mg/kg IP), sulpiride (60 mg/kg IP) or SCH23390 (0.5 mg/kg IP) 10
      20 min prior to restraint. These results indicate that 1) the development of
      sensitization to amphetamine-induced effects on motor activity does not depend on
      the length of exposure to stress (acute or chronic). 2) the stimulation of both
      D1 and D2 dopaminergic receptors is necessary for the development of the
      restraint stress-induced sensitization to AMPH and 3) and opioid system is also
      implicated in this sensitization process.

PMID- 9264062
TI  - Development of tolerance in mice to the sedative effects of the neuroactive
      steroid minaxolone following chronic exposure.
AB  - Minaxolone is a potent ligand for the neurosteroid binding site of the GABAA,
      receptor. In radioligand binding studies to rat brain membranes, minaxolone
      caused a 69% increase in [3H]muscimol binding and a 25% increase in
      [3H]flunitrazepam binding and inhibited the binding of [3H]TBOB with an IC50 of 1
      microM. In mice, minaxolone (100 mg/kg, orally) had marked sedative effects as
      indicated by a reduction in locomotor activity. Chronic dosing with minaxolone
      (100 mg/kg, orally, once daily for 7 days) resulted in a loss of sedative
      response to an acute dose of the drug, indicating development of tolerance.
      Chronic dosing with temazepam (10 mg/kg, orally, once daily for 7 days) resulted
      in the development of tolerance to an acute dose of temazepam; however, the two
      drugs did not appear to be cross-tolerant, indicating that they may have a
      different mechanism of action at the level of the GABAA receptor.

PMID- 9264064
TI  - The relationship of oral chlorpyrifos effects on behavior, cholinesterase
      inhibition, and muscarinic receptor density in rat.
AB  - Behavioral changes and tissue cholinesterase (ChE) inhibition were examined in
      animals treated with the commonly used insecticide chlorpyrifos. Adult male rats
      were dosed by gavage with 0, 10, 30, 60, or 100 mg/kg chlorpyrifos. Rats (n =
      20/dose group) were evaluated using a functional observational battery (FOB) and
      an automated measure of motor activity. All rats were tested the day before
      dosing and at 3.5 h (the time of peak effect) after dosing; half of these (n =
      10/dose) were sacrificed immediately after testing for tissue collection. The
      remaining rats were tested again at 24 h, followed by sacrifice. The following
      tissues were collected from each animal: half brain, individual brain areas from
      the other half of the brain (frontal cortex, hippocampus, striatum, hypothalamus,
      cerebellum, pons/medulla), retina, liver, heart, diaphragm, quadriceps femoris
      muscle, and blood (separated into whole blood, plasma, and erythrocytes). ChE
      activity was measured in all tissues, and muscarinic receptor density was
      assessed as quinuclidinyl benzilate (QNB) binding in all brain regions, heart,
      and retina. The lowest dose produced no behavioral effects but did produce
      significant ChE inhibition in most tissues at 3.5 h. Higher doses produced more
      ChE inhibition and cholinergic signs of toxicity. Partial recovery from
      behavioral effects was evident at 24 h, with little or no corresponding recovery
      of ChE activity. Apparent downregulation of muscarinic receptor density was noted
      only in striatum and pons/medulla of rats treated with the highest dose of
      chlorpyrifos. Correlations for behavioral and biochemical effects were generally
      poor because: a) the low-dose effects on ChE inhibition were not reflected in
      behavioral signs, and b) behavioral signs showed recovery at 24 h, whereas ChE
      activity did not. Examination of data for individual rats indicated that > 60% of
      brain ChE inhibition was reached before neurobehavioral effects were evident.

PMID- 9264065
TI  - Cocaine reward and locomotor activity in C57BL/6J and 129/SvJ inbred mice and
      their F1 cross.
AB  - Large individual differences exist among mice in their behavioral responses to
      drugs of abuse, and many of these differences have a substantial genetic basis.
      The creation of new animal models using recombinant DNA technology has provided
      new genetic tools for assessing the role of specific candidate genes in drug
      response. This study presents a characterization of cocaine activation and reward
      in the two strains used most commonly for production of knockout mice, C57BL/6J
      and 129/SvJ, and their outcrossed F1 offspring. Using conditioned place
      preference, the study demonstrates that there are large strain differences in
      spontaneous locomotor activity and in the rewarding effects of cocaine. The
      129/SvJ strain is hypoactive and is very sensitive to the locomotor activating
      effects of cocaine but does not develop cocaine-conditioned place preference
      under conditions that yield significant place preference in C57BL/6J mice. These
      phenotypes are not inherited in a simple additive manner, but rather the F1
      generation resembles the C57BL/6J progenitor strain for a number of the behaviors
      examined.

PMID- 9264066
TI  - Effects of chlorpromazine on rats' acquisition of lever-press responding with
      immediate and delayed reinforcement.
AB  - The effects of chlorpromazine (0, 2, 6, and 10 mg/kg) on the acquisition of lever
      press responding by rats were examined under conditions where reinforcement
      (water delivery) was immediate or delayed. Under the immediate reinforcement
      condition, water-deprived rats were exposed during 8-h sessions to a fixed-ratio
      1 (FR 1) schedule of water delivery without prior autoshaping or hand shaping.
      Under the delayed reinforcement condition, similar rats were exposed to a tandem
      FR 1 fixed-time 8-s schedule of water delivery. A different squad of eight rats
      was exposed to each delay condition and drug dose. For all subjects, responses on
      one lever produced water and responses on a second lever had no programmed
      consequences. Regardless of whether reinforcement was immediate or delayed,
      chlorpromazine reduced in dose-dependent fashion the mean number of operative
      lever responses emitted, which suggests that the drug interfered with learning.
      At all chlorpromazine doses except 10 mg/kg, substantially more operative-lever
      than inoperative-lever responding occurred, indicating that the operant response
      was acquired. Chlorpromazine at 2 and 6 mg/kg disrupted the acquisition of
      stimulus control by the operative lever when reinforcement was delayed, but not
      when it was immediate. At 10 mg/kg, most subjects did not acquire lever-pressing
      regardless of whether they were exposed to the immediate or delayed reinforcement
      procedure. Procedures similar to those used in the present study appear to
      provide a reasonable assay for examining how drugs affect the initial behavioral
      effects of immediate and delayed reinforcement, and may merit further
      investigation.

PMID- 9264067
TI  - Effects of ibogaine on performance in the 8-arm radial maze.
AB  - The effects of ibogaine were studied in 12 rats trained to perform in an 8-arm
      radial maze. In Phase I, the mean number of sessions to criterion and cumulative
      errors to criterion, as well as mean response rate, were determined for two
      groups of six animals in a task where only four arms were baited. Group 1
      received a potentially neurotoxic dose of ibogaine (50 mg/kg IP administered
      twice, with approximately 8 h between injections), and group 2 received vehicle.
      Both groups had similar levels of performance, but ibogaine-treated subjects had
      a significantly lower rate of responding in the maze. During Phase II, subjects
      were given a range of doses of ibogaine 20 min prior to working in the maze.
      Ibogaine produced a dose-dependent decrease in response rate, but efficiency (%
      arms correct) was not affected. In Phase III, subjects were divided into the same
      groups as they had been in Phase I. Ibogaine (30 mg/kg, IP) or vehicle was
      administered immediately following daily sessions in the maze. Ibogaine-treated
      rats committed significantly fewer errors than those in the vehicle treated
      group. Thus, in the present study, ibogaine failed to produce any deleterious
      effects on either acquisition of a novel task or efficiency in a previously
      learned task.

PMID- 9264068
TI  - Dietary modulation of mu and kappa opioid receptor-mediated analgesia.
AB  - Research has demonstrated that intake of palatable carbohydrates and fats
      enhanced morphine-induced analgesia (MIA) in Sprague-Dawley rats. To determine if
      the effects of palatable foods on nociceptive responses would generalize to other
      strains of animals and other opioid agonists, the present experiments
      investigated whether intake of palatable foods would: a) alter MIA in Long-Evans
      rats, and b) alter analgesia produced by drugs acting at kappa opioid receptors.
      In experiment 1, adult male Long-Evans rats were fed Purina chow alone or chow
      and either a 32% sucrose solution, a 0.15% saccharin solution, or hydrogenated
      vegetable fat. Using a tail-flick apparatus, nociceptive responses, measured as
      percent maximal possible effect (%MPE), were examined after morphine
      administration [0.0, 1.0, 3.0, and 6.0 mg/kg subcutaneously (SC)]. %MPEs varied
      directly as a function of dose and were significantly greater for rats fed chow
      and either sucrose or fat than for rats fed chow alone or chow and saccharin.
      Experiment 2 compared the analgesic effect of the kappa opioid receptor agonist
      U50,488H (0, 5.0, 10.0, and 20.0 mg/kg SC) in rats fed chow alone or chow and a
      32% sucrose solution. Administration of U50,488H led to analgesia. However, %MPEs
      did not vary directly as a function of dose. %MPEs of rats fed chow and sucrose
      were significantly greater than those of rats fed chow alone after injections of
      10.0 and 20.0 mg/kg U50,488H. Experiment 3 compared the analgesic effect of
      U50,488H (5.0, 10.0, 15.0, and 20.0 mg/kg SC) in rats fed chow alone or chow and
      either a 0.15% saccharin solution or hydrogenated vegetable fat. Administration
      of U50,488H led to analgesia. However, %MPEs did not vary directly as a function
      of dose or as a function of diet. %MPEs of rats fed chow and fat were
      significantly greater than those of rats fed chow alone after injection of 5.0
      mg/kg U50,488H.

PMID- 9264069
TI  - Fluoxetine reduces saccharin-induced elevation of fluid intake in alcohol
      preferring Fawn-Hooded rats.
AB  - Previous work has established that saccharin and alcohol intakes are highly
      correlated in a variety of rat strains. In addition, it has been shown that
      alcohol-preferring rats consume saccharin beyond the limit of their normal daily
      fluid intake (DFI). It has been hypothesized that alcohol-preferring rats have
      impaired control over consumption of reinforcing substances, which may be related
      to a deficiency of brain serotonin. In the present study, we examined the effect
      of the serotonin reuptake inhibitor fluoxetine (2.5, 5.0, 10.0 mg/kg, IP, twice a
      day) on saccharin intake in alcohol-preferring Fawn-Hooded (FH) rats. It was
      confirmed that alcohol preferring FH rats almost triple their DFI when
      saccharin/water choice was introduced. Treatment with fluoxetine resulted in a
      dose-dependent decrease in saccharin intake to, but not below, the normal level
      of their DFI. No significant effects of fluoxetine on water intake were observed.
      Despite a significant (up to 69%) decrease in saccharin intake, only a minimal
      reduction (< 4%) in saccharin preference occurred. We conclude that fluoxetine
      reduces the exessive elevation of fluid intake observed at the presence of the
      palatable saccharin solution in Fawn-Hooded rats. These findings may provide more
      evidence for the involvement of the serotonergic system in the brain in exessive
      drinking of rewarding substances.

PMID- 9264070
TI  - The alpha-1 adrenergic agonist, cirazoline, impairs spatial working memory
      performance in aged monkeys.
AB  - The alpha-1 adrenergic agonist, cirazoline, was examined for effects on spatial
      working memory performance in aged rhesus monkeys. Cirazoline has additional high
      affinity for imidazoline receptors and has good brain penetrance when
      administered systemically. Spatial working memory was assessed using the variable
      delayed response task, a test dependent upon prefrontal cortical function in
      monkeys. Low doses of cirazoline (0.00001-0.001 mg/kg) impaired delayed response
      performance significantly. This impairment did not appear to result from
      nonspecific changes in behavior, because cirazoline had no significant effect on
      performance of control trials where the delay was "0" s, and had no significant
      effect on behavioral ratings. Impairment was reversed by pretreatment with the
      alpha-1 adrenergic antagonist, prazosin, consistent with drug actions at alpha-1
      adrenergic receptors. In contrast, preliminary data suggest that higher
      cirazoline doses (0.001-0.01 mg/kg) occasionally produced improved performance
      that was not reversed by prazosin, but rather, by the imidazoline/alpha-2
      adrenergic antagonist, idazoxan. The finding that alpha-1 adrenergic receptor
      stimulation impairs spatial working memory performance complements previous
      research demonstrating that alpha-2 adrenergic receptor stimulation improves
      working memory, and suggests that norepinephrine may have opposing actions at
      alpha-1 vs. alpha-2 receptors in the prefrontal cortex as it does in the
      hypothalamus and thalamus.

PMID- 9264071
TI  - Tolerance to the anticonflict effects of diazepam: importance of methodological
      considerations.
AB  - The present study examines the effects of chronic diazepam treatment on conflict
      behavior in rats using the Geller-Seifter paradigm. A dose-response function for
      the effects of diazepam (DZ) on punished and unpunished responding was determined
      (0.0, 0.63, 1.25, 2.5, and 5.0 mg/kg DZ intraperitoneally) using five independent
      groups. The test doses of DZ produced an inverted U-shaped function where
      punished responding increased as a function of dose up to 2.5 mg/kg and then
      decreased at 5.0 mg/kg. All groups were then treated with 2 x 5 mg/kg DZ per day
      for 5 days. When the dose-response function was redetermined at 36 h post-chronic
      treatment, it was found that the function had shifted to the right, indicating
      tolerance. Because of the inverted U-shaped nature of the original function,
      tolerance was manifested as a decrease in responding on the ascending portion of
      the function and as an increase in responding on the dose (5 mg/kg) representing
      the descending side of the inverted U.

PMID- 9264072
TI  - The effect of cumulative dosing on the analgesic potency of morphine in mice.
AB  - Opioid analgesic potency can be evaluated using cumulative dosing, in which
      subjects are repeatedly administered a drug and tested after each dose until a
      criterion effect is reached. Although many laboratories use cumulative dosing,
      the effects of varying the starting dose and the magnitude of the increment dose
      on morphine analgesia (tail flick) in mice have not been evaluated. In experiment
      1. mice were injected with the same starting dose [0.5 mg/kg subcutaneously (SC)]
      and 30 min later were tested for analgesia. Mice that were not analgesic were
      administered an increment dose (0.5, 1.0, 2.0, 2.5, or 3.0 mg/kg) and retested.
      The process was continued until all mice were analgesic. There was a significant
      effect of increment dose on morphine potency, with the relative potency
      increasing as the increment dose was increased. In experiment 2, different
      starting doses (0.5, 1.0, 2.0, or 3.0 mg/kg) were used with a constant increment
      dose of 1.0 mg/kg. There was a significant effect of starting dose on the potency
      of morphine, with the relative potency increasing as the starting dose increased.
      To determine if increment and starting dose affect tolerance estimates, mice were
      implanted SC with a 25- or 75-mg morphine or placebo pellet for 7 days and then
      tested using cumulative dose-response. Changes in the increment dose
      significantly affected the degree of tolerance for mice implanted with a 25-mg
      morphine pellet but not for mice implanted with a 75-mg morphine pellet. Changes
      in the starting dose did not significantly alter estimates of tolerance. Overall,
      these data indicate that the starting dose and increment dose can impact on
      morphine's potency determined by cumulative dosing protocols. Furthermore,
      estimates of tolerance can be affected by dosing parameters in the cumulative
      dosing protocol. These results suggest that cumulative dosing procedures should
      be standardized across experiments.

PMID- 9264074
TI  - Effects of opioids on the absorption of alcohol.
AB  - Administration of opiate agonists and antagonists has been shown to increase and
      decrease alcohol consumption, respectively. Because opioids can affect gastric
      emptying and decrease intestinal motility, the present experiments were done to
      determine whether changes in alcohol consumption following opioid administration
      might be due to opioid-induced changes in the pharmacokinetics of alcohol. In
      experiment 1, morphine in doses ranging from 1.5 to 4.5 mg/kg dose dependently
      decreased the absorption of alcohol induced by oral intubation (1 g/kg) and
      reduced peak blood alcohol levels (BALs). Naltrexone in doses ranging from 1.5 to
      4.5 mg/kg produced a small, but significant, reduction in the absorption of
      alcohol, but the effects were not dose related. Similar effects of morphine and
      naltrexone on alcohol absorption were observed in rats infused with alcohol (1
      g/kg) through an implanted intragastric cannula. The effects of morphine on
      alcohol absorption were observed whether alcohol levels were determined from tail
      vein or arterial blood samples or from brain samples. The effects of morphine on
      alcohol absorption were not blocked by pretreatment with methyl-naltrexone.
      However, the peripherally acting opioid agonist loperamide reduced BALs in a
      manner similar to morphine. These studies indicate that although opiate agonists
      and antagonists modify alcohol absorption to different extents, their effects on
      BALs are not a sufficient condition to induce changes in alcohol consumption.

PMID- 9264073
TI  - Changes in rat spleen cannabinoid receptors after chronic CP-55,940: an
      autoradiographic study.
AB  - We examined whether cannabinoid receptor density changes in the rat spleen after
      in vivo chronic exposure to cannabinoids. Rats received daily injections of 0.4
      mg/kg IP of the synthetic cannabinoid receptor ligand CP-55,940 for 11 days. One
      h after the last injection on day 11, the rats were killed and spleen coronal
      sections were processed for receptor binding autoradiography with 10 nM of [3H]CP
      55,940 in the absence or presence of unlabeled CP-55,940 (10 microM).
      Densitometric analysis of the autoradiograms showed significant loss of [3H]CP
      55,940 binding of about 42% in chronic cannabinoid-treated, tolerant rats. Our
      findings indicate that cannabinoid receptors basically present in immune spleen
      cells are down-regulated by chronic exposure to cannabinoids, suggesting a role
      in immune modulation and in the impairment of immune function.

PMID- 9264075
TI  - Marmoset conspecific confrontation: an ethologically-based model of anxiety.
AB  - A method of measuring confrontation-induced behavioural changes in common
      marmosets (Callithrix jacchus) together with automated monitoring of locomotor
      activity has been developed as a possible model of anxiety. Recording both
      affiliative and agonistic behaviours between male/female pairs of marmosets and
      using diazepam as a reference drug, it has been possible to define a profile of
      behavioural changes which could be regarded as representing an anxiolytic
      response. Unfamiliar male/female pairs of marmosets were brought into close (non
      contact) proximity in a controlled environment, in which their locomotor activity
      was recorded automatically. Simultaneously, their interactive behaviour was
      assessed by an independent observer via closed-circuit television. The following
      behaviours were analysed: aggressive postures, allogrooming, scratching, anxiety
      related behaviours, social contact and self-grooming. Administration of diazepam
      at 1 and 3.5 mg/kg PO induced a significant (compared to control) reduction in
      scratching, aggressive behaviours, anxiety-related behaviours and an increase in
      allogrooming without affecting locomotor activity during confrontation. Differing
      responses dependent on gender were not found, nor did gender influence the effect
      of treatment on behaviour. Habituation to repeated confrontation did not occur.
      The results from this study demonstrate that this method can be used to measure
      anxiolytic activity in an objective manner.

PMID- 9264076
TI  - Comparative effects of alcohol and marijuana on mood, memory, and performance.
AB  - This study compared subjective and behavioral effect profiles of alcohol and
      smoked marijuana using technology that controlled puffing and inhalation
      parameters. Male volunteers (n = 5) with histories of moderate alcohol and
      marijuana use were administered three doses of alcohol (0.25, 0.5, or 1.0 g/kg),
      three doses of marijuana [4.8, or 16 puffs of 3.55% delta 9-tetrahydrocannabinol
      (THC)], and placebo in random order under double blind conditions in seven
      separate sessions. Blood alcohol concentration (10-90 mg/dl) and THC levels (63
      188 ng/ml) indicated that active drug was delivered to subjects dose dependently.
      Alcohol and marijuana produced dose-related changes in subjective measures of
      drug effect. Ratings of perceived impairment were identical for the high doses of
      alcohol and marijuana. Both drugs produced comparable impairment in digit-symbol
      substitution and word recall tests, but had no effect in time perception and
      reaction time tests. Alcohol, but not marijuana, slightly impaired performance in
      a number recognition test. These data are useful for understanding the relative
      performance impairment produced by alcohol and marijuana at the delivered doses
      and the relationship between their subjective and behavioral effects.

PMID- 9264077
TI  - Dopaminergic and cholinergic interaction in cataleptic responses in mice.
AB  - The cataleptogenic effects of haloperidol, a dopamine D2 receptor antagonist;
      SCH23390, a D1 receptor antagonist; physostigmine, a cholinesterase inhibitor;
      and pilocarpine, a muscarinic M1 receptor agonist, were challenged by
      pretreatment of mice with SKF38393, a dopamine D1 receptor agonist; apomorphine,
      a dopamine D1/D2 receptor agonist (mainly D2 receptor); pirenzepine, a muscarinic
      M1 receptor antagonist; and scopolamine, a muscarinic M1/M2 receptor antagonist.
      The effect of physostigmine and pilocarpine on haloperidol and SCH23390
      cataleptic responses was also examined. Each of the challenging agents blocked
      one or more of the cataleptogenic agents, but only scopolamine blocked all four.
      Pirenzepine blocked cataleptic responses induced by SCH23390 and pilocarpine, but
      not those by haloperidol and physostigmine. The results of this study suggest
      that the action of physostigmine (endogenous acetylcholine) on M2 receptors might
      be more potent than that on muscarinic M1 receptors. A further interesting
      observation was that the haloperidol-induced catalepsy was enhanced by
      physostigmine pretreatment, but not by pilocarpine pretreatment, whereas the
      SCH23390-induced catalepsy showed the opposite spectrum of enhancement by the two
      cholinergic agonists. We conclude that, although the four cataleptogenic agents
      act via the dopaminergic-cholinergic systems, their pharmacological differences
      may be due largely to the different receptor subtypes that are involved in the
      mediation of catalepsy produced by each agent. Thus, dopamine receptors not only
      influence the cholinergic muscarinic receptors, but muscarinic M1 and M2
      receptors also might mediate dopamine D1 and D2 receptor responses, respectively.
      The results suggest that there are, at the least, relationships between
      muscarinic M1 receptors and dopaminergic D1 receptors, and between muscarinic M2
      receptors and dopaminergic D2 receptors. Dopamine D1 and D2 receptors may
      interact in a synergistic fashion on dopaminergic systems, but act independently
      of each other in influencing other system such as cholinergic neurons.

PMID- 9264078
TI  - Alpha 2-adrenoceptor agonists and stress-induced analgesia in rats: influence of
      stressors and methods of analysis.
AB  - The present experiments were designed to investigate the role of housing and
      handling conditions during testing, as well as data analysis, on the outcome of
      antinociceptive testing of alpha 2-adrenoceptor agonists, fentanyl, and a high
      dose of chlordiazepoxide in the tail withdrawal reaction test (TWR test) in rats.
      Dose-response curve data were obtained with fentanyl, clonidine, xylazine,
      dexmedetomidine, and 40.00 mg/kg chlordiazepoxide and were compared under normal
      TWR test conditions and during immobilization or immobilization with continuous
      painful stimulation. Data were analyzed in terms of all-or-none criteria as well
      as percentage maximum possible effect (%MPE) analysis over the total measurement
      period or at any specific time point during testing. The results indicate that
      stress, induced by immobilization and immobilization with long-term-applied paw
      pressure, unmasked possible antinociceptive properties of the various alpha 2
      adrenoceptor agonists and potentiated the effects of fentanyl. Stress also
      unmasked the positive effects of benzodiazepines. The manner of data analysis was
      shown to significantly affect the outcome measured in stress and nonstress
      conditions. The MPE analysis, particularly at one time point, appeared much more
      sensitive than the all-or-none criteria. The data indicate that the housing and
      handling conditions of animals during testing, together with data analysis, may
      affect the outcome of different classes of compounds in the TWR test, and this
      knowledge may help control for false positive results.

PMID- 9264079
TI  - GABAergic drugs inhibit amphetamine-induced distractibility in the rat.
AB  - Drugs facilitating GABAergic neurotransmission have been reported to block some
      behavioral actions of dopaminergic stimulation but not others. The present
      experiments were performed with the purpose to extend the range of behaviors in
      which the interaction between GABA and dopamine have been studied. The ability of
      the GABAB agonist baclofen and the GABA transaminase inhibitor sodium valproate
      to block the enhanced distractibility produced by amphetamine was evaluated in a
      procedure especially designed for analyzing drugs' effects on distractibility.
      Briefly, rats were trained to traverse a straight runway with a sucrose solution
      as reinforcement. Once the response had been acquired, an additional runway
      ending in an empty box was connected. The time spent investigating this
      additional runway is the measure of distractibility. Male rats treated with
      amphetamine, 1 mg/kg, displayed an increase of the time spent in the additional
      runway. Baclofen, 2.5 and 5 mg/kg, and sodium valproate, 100 and 200 mg/kg, had
      no effect on distraction behavior when administered alone. However, when these
      drugs were administered together with amphetamine, 1 mg/kg, they completely
      inhibited the effects of the stimulant on distractibility. These data show that
      distractibility is similar to discrimination learning with regard to the capacity
      of GABAergic drugs to block the effects of dopaminergic stimulation. It is
      different from locomotor activity, however, where GABAergic drugs are ineffective
      in this respect.

PMID- 9264080
TI  - The conditioned eyeblink response: a role for the GABA-B receptor?
AB  - In well-trained animals, infusion of the GABA-B agonist baclofen into the
      cerebellar interpositus nucleus and overlying cortex abolished the conditioned
      response (CR) with no effect on the unconditioned response (UR) with doses at or
      above 5.0 mM. Infusion of the GABA-B antagonist CGP 5584-5A alone had no effect
      on the CR or UR. However, administration of 5 mM baclofen soon after infusion of
      CGP 5584-5A (15 min) resulted in no reduction of percent CR and only partial
      reduction of CR amplitude. Naive animals given interpositus infusions of baclofen
      during training showed no learning, yet learned normally in postinfusion
      training. The distribution of (radiolabelled) baclofen was localized and remained
      within the cerebellum. The results presented here are consistent with a growing
      body of literature supporting the hypothesis that the memory trace for eyeblink
      conditioning is formed and stored in the cerebellum and may involve GABAergic
      mechanisms.

PMID- 9264081
TI  - Dosage choices of rats for morphine, for heroin, and between morphine and heroin.
AB  - Each of four doses of intravenous morphine and four of intravenous heroin was
      tested for reinforcing efficacy, and comparisons were made among the four
      morphine doses, among the four heroin doses, and between morphine and heroin.
      Rats with venous catheters performed one daily forced run for 75 s to one of the
      two compartments of a spatial choice apparatus, with compartments and doses or
      drugs alternating over days. In each trial, the accessible compartment depended
      on which dose (including zero dose) or drug a rat was to receive. After 18-28
      forced trials and 0 or 4 reinforced choice trials, efficacies of the different
      doses and drugs were measured by subsequent compartment choices. Increasing dose
      effects on choice were found for morphine (0.32, 1.0, 3.2, and 10.0 mg/kg
      intravenously) and for heroin (0.032, 0.10, 0.32, and 1.0 mg/kg intravenously). A
      32:1 morphine:heroin dose ratio produced nearly equal choice. Dose effects were
      more evident in within-subjects experiments (each rat received two doses or two
      drugs) than in between-subjects experiments (each rat received one dose of one
      drug.

PMID- 9264082
TI  - Hyperactivity induced by prenatal nicotine exposure is associated with an
      increase in cortical nicotinic receptors.
AB  - Prenatal exposure to nicotine may lead to hyperactivity. To evaluate possible
      involvement of central nicotinic receptors in this condition, pregnant Sprague
      Dawley rats were implanted with osmotic minipumps to receive nicotine (6
      mg/kg/day) or saline throughout gestation. A total of 222 pups (118 males and 104
      females) from 24 dams were measured for locomotor activity. Male and female
      hyperactive and nonhyperactive offspring from each treatment group were selected
      and analyzed for nicotinic receptor concentrations in various brain regions.
      Hyperactive male offspring that were prenatally exposed to nicotine exhibited a
      significant increase in the cortical receptor densities without a change in
      binding affinity. Hyperactive offspring of saline-treated dams did not show an
      increase in cortical nicotinic receptors. These results suggest that hyperactive
      male offspring of nicotine-exposed dams are also susceptible to neurochemical
      effects of intrauterine nicotine exposure.

PMID- 9264083
TI  - The analgesia-enhancing component of ingested amniotic fluid does not affect
      nicotine-induced antinociception in naltrexone-treated rats.
AB  - Ingestion of amniotic fluid and placenta by rats has been shown to enhance opioid
      mediated antinociception but not affect the nonopioid-mediated antinociception
      produced by aspirin, suggesting specificity for opioid-mediated processes.
      However, enhancement by the active substance(s) in amniotic fluid and placenta
      (POEF, for placental opioid-enhancing factor) of antinociception produced by
      other nonopioid mechanisms has yet to be examined. The present experiments tested
      whether ingestion of amniotic fluid enhances the antinociception produced by
      nicotine injection. In Experiment 1A, enhancement of morphine-mediated
      antinociception by ingestion of amniotic fluid was demonstrated in a hot-plate
      assay. In Experiment 1B, rats pretreated with naltrexone were given an orogastric
      infusion of amniotic fluid or control (0.25 ml), then injected with nicotine (0,
      0.075, 0.125, or 0.225 mg/kg subcutaneously), then tested for antinociception in
      a hot-plate assay. Amniotic fluid ingestion did not enhance the antinociception
      produced by various doses of nicotine. In Experiment 2, rats pretreated with
      naltrexone were given an orogastric infusion of amniotic fluid (0, 0.125, 0.25,
      or 0.50 ml) and then injected with 0.125 mg/kg nicotine. None of the doses of
      amniotic fluid enhanced the nicotine-induced antinociception. The findings of
      these experiments lend support to our contention that the enhancement by POEF of
      antinociception is specific to opioid-mediated processes.

PMID- 9264084
TI  - Interaction of morphine and haloperidol on agonistic and motor behaviors of male
      mice.
AB  - To further clarify the interaction between opioid and dopaminergic systems, the
      effects of simultaneous administration of morphine hydrochloride (1.25 or 2.5
      mg/kg) and haloperidol (0.1 mg/kg) on aggressive behavior of male mice were
      explored. Isolated male mice (experimental animals) were confronted in a neutral
      area with anosmic, group-housed consepecifics (standard opponents) 30 min after
      injection of both compounds, and aggression was evaluated by estimation of times
      allocated to 11 different behavioral categories. In the first experiment (which
      functioned as a pilot study), the two doses of morphine were explored. In the
      second one, incorporating a more complete experimental design, only the lowest
      morphine dose was used and the animals were preselected by a previous aggression
      test. In attack behavior, morphine added to haloperidol counteracted, at least
      partially, the antiaggressive effect of the neuroleptic. In contrast, the
      impairing effects of haloperidol on motor activity were increased by the addition
      of morphine. These results show that the behavioral effects of dopaminergic
      antagonists are modulated by opioid influences and that opiates and dopaminergic
      agents interact in a different manner on motor and on aggressive behaviors.

PMID- 9264085
TI  - The behavioral effects of NMDA antagonists in serotonin depleted rats.
AB  - The influence of serotonin (5-HT) depletion (5,7-dihydroxytryptamine, 5,7-DHT,
      250.0 micrograms, ICV), on behavioral effects of non-competitive (MK-801) and
      competitive (CGP 37849) NMDA antagonists, was examined in rats. 5,7-DHT induced
      very potent and long lasting decrease in the 5-HT concentration in the brainstem
      and limbic forebrain. One week after 5,7-DHT administration, dopamine metabolism
      was found enhanced in the brainstem. The lesion did not change rat baseline motor
      and exploratory activity, but it significantly disinhibited animals' behavior
      suppressed by shock, in the Vogel test. Serotonin depletion revealed locomotor
      stimulating effect of MK-801, administered IP at the doses of 0.05 and 0.2 mg/kg.
      However, no change in striatal dopamine metabolism was detected in rats injected
      with the same dose of MK-801 (0.2 mg/kg), and examined one week after
      serotonergic denervation. Serotonergic lesions antagonized both enhancements of
      exploratory behavior, and motor suppression produced by the dose of 1.0 and 10.0
      mg/kg of CGP 37849, respectively. Thus, 5,7-DHT-induced lesions influenced in a
      complex way the effects of NMDA antagonists. It is reasoned, that enhancement of
      motor stimulating effects of MK-801 in neurotoxin pretreated animals, reflects
      synergistic disinhibition of activity of dopaminergic neurons by MK-801 and
      serotonin depletion. On the other hand, antagonism of CGP 37849-caused motor
      depression can be explained by the lowering influence of 5,7-DHT on serotonin
      content. It is known that the release of serotonin is strongly stimulated by
      higher doses of CGP 37849, and takes part in the expression of some symptoms of
      the serotonin-like syndrome, including motor disturbances.

PMID- 9264086
TI  - Kainate microinjection into the dorsal raphe nucleus induces 5-HT release in the
      amygdala and periaqueductal gray.
AB  - Earlier results obtained in one of our laboratories showed that microinjection
      into the dorsal raphe nucleus (DRN) of the excitatory amino acid kainic acid, the
      benzodiazepine (BZD) inverse agonist FG 7142, and the 5-HT1A receptor agonist 8
      OHDPAT changed the behavior of rats in the elevated T-maze, an animal model of
      anxiety. The present study investigates biochemical correlates of these results
      in awake rats by measuring 5-HT release with in vivo microdialysis in two brain
      structures innervated by the DRN-the amygdala (Am) and the dorsal periaqueductal
      gray matter (DPAG)-that have been implicated in anxiety. Microinjection of kainic
      acid (60 pmol) into the DRN significantly increased 5-HT release in both the Am
      and the DPAG. In the DPAG, the increase was 14-fold higher with respect to the
      baseline and occurred only at the first sample, which was collected 30 min after
      the injection. In the Am, the increase was less pronounced (nearly fourfold) but
      persistent, lasting until the fourth sample, which was collected 120 min from the
      injection. FG 7142 (40 pmol) and 8-OH-DPAT (8 nmol) were ineffective. Because
      only intra-DRN kainate both increased inhibitory avoidance and decreased one-way
      escape in the elevated T-maze, the present behavioral results support the
      suggestion that 5-HT facilitates conditioned fear in the Am and inhibits
      unconditioned fear in the DPAG.

PMID- 9264087
TI  - Effects of caerulein and CCK antagonists on tolerance induced to morphine
      antinociception in mice.
AB  - Different groups of mice received one daily dose (50 mg/kg) of morphine
      subcutaneously (SC) for 3, 4 or 5 days to develop tolerance to the opioid. The
      antinociceptive response of morphine (9 mg/kg) was tested in the hot-plate test
      24 h after the last dose of the drug. Tolerance to morphine was obtained in all
      groups. The group of mice that received morphine for 4 days was employed for the
      rest of the experiments. Pretreatment of animals with a single dose of caerulein
      (0.025, 0.05, and 0.1 mg/kg, SC) 30 min prior to receiving morphine (50 mg/kg;
      during the development of tolerance to the opioid) on day 1, 2, 3, 4 or 5 of
      morphine administration potentiate antinociception induced by morphine (test dose
      of 9 mg/kg). The dose of 0.05 mg/kg of caerulein, used 30 min before morphine
      administration on day 3, was also used to evaluate the effects of antagonists on
      caerulein-induced decrease in tolerance. The selective cholecystokinin (CCK)
      receptor antagonists, MK-329 [1-methyl-3-(2 indoloyl)amino-5-phenyl-3H-1,4
      benzodiazepin-2-one; 0.25 and 0.5 mg/kg] or L-365,260 [3R(+)-N-(2,3-dihydro-1
      methyl-2-oxo-5-phenyl-1H- 1,4-benzodiazepin-3-yl)-N-(3-methyl-phenyl)urea: 0.25
      and 0.5 mg/kg] decreased potentiation of morphine response induced by caerulein.
      MK-329 or L-365,260, when were injected 35 min before morphine injection during
      the development of tolerance and on day 3, decreased the tolerance to morphine. A
      single administration of MK-329 or L-365,260 (in the absence of caerulein) 35 min
      and 48 h before the test dose of morphine (9 mg/kg) potentiated the
      antinociception of morphine in nontolerant animals. In conclusion, CCK
      mechanism(s) may interact with morphine tolerance.

PMID- 9264088
TI  - Biphasic emetic response of cyclophosphamide in the ferret.
AB  - Cyclophosphamide (177 mg/kg, IV: n = 8) produced a biphasic emetic response in
      the ferret with a mean +/- SE of 23.3 +/- 4.0 emetic episodes during a 4-h
      observation period. The emetic profile of cyclophosphamide showed a first phase
      with 18.6 +/- 3.9 episodes and a second phase with 4.7 +/- 1.2 episodes.
      Ondansetron (0.07 and 0.13 mg/kg, IV) and droperidol (0.25 and 0.79 mg/kg, IV)
      significantly reduced the number of emetic episodes in the first phase.
      Metoclopramide (2.24, 4.08, and 7.07 mg/kg, IV) also significantly reduced the
      number of emetic episodes in the first phase, and the dose of 7.07 mg/kg
      completely prevented emetic episodes in the second phase. In addition,
      ondansetron-treated ferrets (0.04, 0.07, and 0.13 mg/kg, IV) had a significant
      increase in the number of emetic episodes in the second phase.

PMID- 9264089
TI  - Bromocriptine enhances feeding behavior without changing dopamine metabolism.
AB  - Bromocriptine is an ergot derivative and has been thought to act as a selective
      D2 receptor agonist, but its effects on dopamine release in vivo have not been
      confirmed. We administered bromocriptine into the striatum of rats and studied
      the effects on feeding behavior and dopamine release. Bromocriptine was perfused
      via a microdialysis probe into the ventrolateral striatum of rats fasted for 22
      h, and the rats were then allowed to feed freely for 6 h. Bromocriptine perfusion
      increased food intake in a dose-dependent manner, whereas the extracellular
      concentrations of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and
      homovanillic acid (HVA) did not change. Perfusion of (-) sulpiride, a selective
      D2 receptor antagonist, decreased food intake, but increased dopamine release and
      the levels of DOPAC and HVA. Pretreatment with (-)sulpiride perfusion for 1 h
      prior to bromocriptine perfusion inhibited the increase of food intake induced by
      bromocriptine, and it increased dopamine release and the levels of DOPAC and HVA.
      These findings suggest that bromocriptine directly perfused into the
      ventrolateral striatum acts selectively on postsynaptic D2 receptors and enhances
      feeding behavior.

PMID- 9264091
TI  - Chronic ethanol ingestion-induced changes in open-field behavior and oxidative
      stress in the rat.
AB  - The effects of chronic ethanol intoxication on the open-field behavior, on
      antioxidant enzyme activities, and the degree of lipid peroxidation were
      investigated. Rats consuming a liquid diet containing 7% ethanol for 4, 7, 14, or
      21 days exhibited a significantly decreased ambulation activity, accompanied by a
      reduced frequency and duration of explorative rearing in an open-field task 4, 7,
      and 14 days after chronic ethanol ingestion, whereas presumed adaptation to the
      neurologic effects of ethanol was observed on day 21. Changes in the activities
      of glutathione peroxidase (GSH-Px): glutathione reductase (GSH-R), and catalase,
      and in the content of reduced glutathione (GSH) in blood samples were determined
      by means of biochemical methods. The degree of lipid peroxidation was measured
      via thiobarbituric acid assays. Chronic ethanol ingestion elicited a significant
      increase in GSH-Px activity (by a maximum of approximately 32% on day 14),
      whereas opposite alterations in GSH-R and catalase activities were recorded (49%
      of the control value on day 4 and 17% on day 21, respectively). Highly elevated
      contents of thiobarbituric acid reactive substances reflected extensive lipid
      peroxidation processes throughout the experiment. These changes indicate that
      ethanol toxicity induces profound changes in explorative behavior, mediated, at
      least partly, by changes in the free radical metabolism.

PMID- 9264090
TI  - Influence of continuous levels of fentanyl in rats on the mu-opioid receptor in
      the central nervous system.
AB  - The highly potent and efficacious mu-opioid agonist fentanyl was SC infused into
      rats with submaximal analgesic doses (0-1.14 mumol/kg/day) continuously for 8
      days, checked by the constant daily urinary recovery of intact drug (0.43 +/-
      0.031% of the daily dose). Tail-flick latencies measured at 24 (day 1) and 48 h
      (day 2) after starting the infusion were increased in a dose-dependent fashion
      compared with those before the infusion (day 0). However, at day 8, the latencies
      were increased only weakly, not significantly, revealing tolerance to the
      antinociceptive activity of fentanyl. Fentanyl at all doses showed no significant
      effect on the capacity (Bmax) and affinity (Kd) of the mu-opioid receptor binding
      of DAMGO to whole brain (Bmax 126.2 +/- 3.00 fmol/mg protein, Kd 1.00 +/- 0.04
      nM) and spinal cord (Bmax 48.24 +/- 2.71 fmol/mg protein, Kd 1.93 +/- 0.13 nM)
      membranes gained from the rats after killing them at day 8. Gpp(NH)p increased
      the Kd for brain and spinal cord sites by 3.09 and 2.65, respectively,
      independent of the fentanyl dose. The infusion with fentanyl did not after the
      basal and forskolin-stimulated adenylate cyclase activity in the whole brain
      membranes, nor did it change the inhibition of the forskolin-stimulated activity
      by DAMGO. It is concluded that, in rats, constant long-term body levels of highly
      potent mu-agonists result in a tolerant state that, however, does not produce
      overall changes in the parameters of their specific receptor sites in the CNS,
      i.e., receptor capacity and affinity, and in the events closely related to them,
      i.e., their regulation by GTP and of adenylate cyclase. This does not exclude
      such possible changes to be restricted to specific regions in the CNS.

PMID- 9264092
TI  - Effects of brief caffeinated-beverage deprivation on mood, symptoms, and
      psychomotor performance.
AB  - The effects of short-term deprivation of caffeinated beverages on mood,
      withdrawal symptoms, and psychomotor performance were studied in habitual coffee
      drinkers. Twenty-four male and female coffee drinkers were tested at midday (1130
      1330 h) under two conditions. On one day they consumed caffeinated beverages ad
      lib prior to testing, and on the other they remained caffeine abstinent. The
      order of treatments was counterbalanced. Mood and withdrawal symptom reports were
      collected by questionnaires. Psychomotor performance was tested with a
      computerized test battery. Caffeinated-beverage deprivation was associated with
      decreased vigor and increased fatigue and with symptoms including headache. No
      changes in psychomotor performance were observed. Even short periods of
      caffeinated-beverage deprivation, equivalent in length to missing regular morning
      coffee, can produce noticeable unpleasant caffeine-withdrawal symptoms by the
      middle of the day. These symptoms may be a common side effect of habitual
      caffeinated beverage consumption.

PMID- 9264093
TI  - Effect of combinations of insulin, glucose and scopolamine on radial arm maze
      performance.
AB  - Previous research has shown that glucose is an effective agent in facilitating
      memory performance and in attenuating scopolamine-induced amnesia. Although
      insulin has not been shown to facilitate unimpaired memory, a previous study has
      demonstrated that insulin can also attenuate scopolamine-degraded memory. The
      present study was designed to determine how different combinations of insulin,
      glucose and scopolamine affect memory. It involved nine rats whose memory was
      assessed through performance in a win-shift radial arm maze task under different
      drug treatments. A 2 x 2 x 2 (insulin x glucose x scopolamine) within-subjects
      design with a 5-h drug test interval was employed. Scopolamine disrupted memory
      performance, and both glucose and insulin counteracted this disruption. Combining
      the glucose and insulin treatments did not increase their ability to attenuate
      scopolamine deficits but slightly decreased this effect. Glucose tended to
      enhance memory, even in the absence of scopolamine, whereas insulin had no effect
      on memory in the absence of scopolamine. Blood glucose levels were measured and
      did not indicate changes caused by drug treatments. The memory effects may have
      been due to the acetylcholine-agonist actions of glucose and insulin, an
      interpretation consistent with previous research findings.

PMID- 9264094
TI  - Active immunization with cocaine-protein conjugate attenuates cocaine effects.
AB  - Immunization with cocaine-keyhole limpet hemocyanin (KLH) conjugate elicited the
      formation of anti-cocaine antibody sufficient to blunt the effects of cocaine in
      rats. Cocaine was bound to KLH for immunization with the photoactivatable
      crosslinker N-hydroxysuccinimide-4-azidobezoate (HSAB). Immunization with the
      cocaine-KLH-complete Freund's adjuvant complex was effective in attenuating the
      analgesic and reinforcing effects of cocaine in laboratory rats. Enzyme-linked
      dot blot assay revealed the presence of anti-cocaine antibody in serum.
      Competitive binding studies suggest that the antibody was specific to cocaine.
      Active immunization for cocaine may provide an alternative to drug treatment and
      may provide protection from addiction.

PMID- 9264095
TI  - Dorsal raphe and substantia nigra response to flumazenil in diazepam-dependent
      rats.
AB  - Flumazenil (FLU; 25 micrograms) and DMSO-vehicle were focally injected (1
      microliter) into the substantia nigra (SN) and the dorsal raphe nucleus (DR) in
      rats chronically implanted with silastic capsules containing diazepam (DZ; 540
      mg/week). FLU precipitated an abstinence syndrome in the SN as indicated by a
      significant abstinence score, several abstinence signs and reduced total power of
      the fast frequency bands of the electroencephalogram (EEG) in the injections
      sites frontal cortex, (FC) and hippocampus (H). In contrast, FLU did not produce
      an abstinence syndrome in the DR, and its effect on the power of the EEG in DR,
      FC and H was not significantly different from that of the DMSO-vehicle. The data
      show regional heterogeneity in the response of the SN and the DR to chronic DZ
      treatment in terms of a focally precipitated abstinence syndrome.

PMID- 9264096
TI  - Behavioral and autonomic thermoregulation in the rat following propylthiouracil
      induced hypothyroidism.
AB  - A reduced body temperature is a common symptom of hypothyroidism and may result
      from a deficiency in metabolic heat production. However, a reduced metabolism
      does not necessarily imply a failure in thermoregulatory control if other
      thermoeffectors, in particular behavioral thermoregulation, are operative. To
      address this issue, selected ambient temperature (Ta) in a temperature gradient,
      core temperature (Tc), heart rate (HR), and motor activity (MA) were monitored
      via radiotelemetry in euthyroid rats and rats made hypothyroid by the
      administration of 0.05 mg/ml propylthiouracil (PTU) in drinking water for
      approximately 15 days. Core temperature of PTU-treated rats was reduced by 0.3
      degree, whereas selected Ta was increased by 2.3 degrees. PTU treatment led to
      significant reductions in HR, whereas MA was unaffected. Thermoregulatory
      behavior did not reverse the PTU-induced hypothermia, suggesting that PTU-induced
      hypothyroidism leads to a regulated reduction in body temperature (i.e., decrease
      in the set point). A reduced set point seems to be an adaptive response that
      lowers the metabolic requirements for thermoregulation in the hypothyroid rat.

PMID- 9264097
TI  - Isobolographic analysis of the interaction between epidural sufentanil and
      bupivacaine in rats.
AB  - The present study was performed to evaluate the nature of the interaction between
      epidurally administered sufentanil and bupivacaine in producing antinociception
      in rats. Rats in which epidural catheters had been inserted received epidural
      injections with bupivacaine and sufentanil. Nociception was tested by use of the
      tail-withdrawal reaction (TWR) test and the hot-plate test. Isobolographic
      analyses were performed with fixed and variable dose ratio treatment schedules
      based on the ED50s and the highest inactive concentrations of the compounds in
      both tests. In the TWR test, a synergistic interaction was obtained between the
      two compounds independent of whether a variable dose ratio regimen (with either
      0.08 microgram/rat sufentanil or 80 micrograms/rat bupivacaine as the preset
      component) or a fixed dose ratio of 1/1,000 sufentanil/bupivacaine (based on the
      individual ED50s) was used. In the hot-plate test, a synergistic interaction was
      observed only in the variable dose ratio regimen with 0.08 microgram/rat
      sufentanil as the preset component and in the fixed dose ratio regimen of 1/1,000
      sufentanil/bupivacaine (a ratio based on the ED50 values of the TWR test) but not
      with a ratio of 1/200, as demonstrated by the ED50s of both drugs in the hot
      plate test. The interaction between epidurally administered bupivacaine and
      sufentanil seems to be synergistic for both tests when variable and fixed dose
      ratios are used. The synergism could be more easily demonstrated in the TWR test.
      For drugs with a segmental action, the hot-plate test seems to be less optimal.
      The necessity of a minimal critical amount of bupivacaine to obtain synergism may
      have clinical implications.

PMID- 9264098
TI  - Perinatal exposure to morphine disrupts brain norepinephrine, ovarian cyclicity,
      and sexual receptivity in rats.
AB  - The effect of perinatal exposure to morphine on the development of
      catecholaminergic and reproductive function in female rats was investigated.
      Adult rats received morphine intraperitoneally daily for 40 days. The dose of
      morphine was progressively increased at 10-day intervals from 5, 7.5, 10 to 15
      mg/kg body weight until day 40. The rats were mated between days 38 and 45.
      Administration of morphine at dose rates of 20 and 30 mg/kg continued during
      pregnancy. The dose was increased to 40 mg/kg for 10 days postpartum. Results
      showed that morphine disrupted ovarian cyclicity in 52% of the females. Amongst
      the remaining females, 43% became pregnant when mated. In the female offspring
      born to such dams, sexual maturation was delayed and body weight was reduced
      until weaning. At adulthood, lordosis behavior was inhibited when the female
      offspring were tested against stimulus males. Plasma estradiol and ovarian
      estradiol and progesterone levels were reduced. Norepinephrine concentration in
      the hypothalamus was reduced, whereas it remained unchanged in the amygdala.
      Dopamine concentrations in both hypothalamus and amygdala were not influenced by
      perinatal morphine exposure. These results suggest that chronic morphine
      treatment during perinatal life selectively influences the development of
      noradrenergic mechanisms in the rat brain and this may in turn be responsible for
      reduced reproductive activity.

PMID- 9264099
TI  - NMDA but not AMPA receptor antagonists impair the delay-interposed radial maze
      performance of rats.
AB  - The effects of the N-methyl-D-aspartate (NMDA) receptor antagonists CGS19755 and
      MK801 and the 2-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA)
      receptor antagonist YM90K on spatial working memory were investigated by using a
      delay-interposed radial-arm maze (RAM) task in rats. CGS19755 and MK801, at the
      largest dose that had no effect on the performance in the nondelayed RAM task,
      significantly decreased the initial correct response after the 5-min delay in the
      delay-interposed RAM task. In contrast, YM90K had no effect on the initial
      correct response and arm reentries in both the delay-interposed and nondelayed
      RAM task. CGS19755, MK801 and YM90K, at all doses tested, did not alter the
      running time in either the delayed or the nondelayed RAM tasks. These results
      suggest that spatial working memory can be impaired by a blockade of NMDA
      receptor function and that such impairment is particularly sensitive to delay
      interposition. The lack of effect of the AMPA receptor antagonist provides
      additional evidence of the importance of the NMDA subtype of the glutamate
      receptors in cognitive processes.

PMID- 9264100
TI  - Acute and subchronic effects of tiapride on isolation-induced aggression in male
      mice.
AB  - Although the antiaggressive properties of several atypical neuroleptics are
      known, the actions of tiapride (a selective dopaminergic D2-receptor antagonist)
      on agonistic behavior have not been explored and there are no studies comparing
      acute and subchronic effects of this compound on aggression in rodents. In this
      work, the effects of tiapride (20-100 mg/kg, IP), administered acutely or
      subchronically for 10 days, on agonistic behaviour elicited by isolation in male
      mice were examined. Individually housed mice were exposed to anosmic "standard
      opponents" 30 min after drug administration, and the encounters were videotaped
      and evaluated using an ethologically based analysis. Tiapride decreased time
      spent in offenssive behaviors significantly, without an impairment of motor
      activity (60 and 80 mg/kg). Moreover, no tolerance to tiapride antiaggressive
      activity was observed after repeated administration of the drug. On the contrary,
      the action on immobility showed a clear tolerance development with repeated
      injections (100 mg/kg). The divergence found in the temporal course of tolerance
      to tiapride in its antiaggressive and motor effects is discussed.

PMID- 9264101
TI  - NMDA receptor complex blockade by oral administration of magnesium: comparison
      with MK-801.
AB  - The ion channel of the N-methyl-D-aspartate (NMDA) receptor complex is subject to
      a voltage-dependent regulation by Mg2+ cations. Under physiological conditions,
      this channel is supposed to be blocked by a high concentration of magnesium in
      extracellular fluids. A single dose of magnesium organic salts (i.e., aspartate,
      pyroglutamate, and lactate) given orally to normal mice rapidly increases the
      plasma Mg2+ level and reveals a significant dose-dependent antagonist effect of
      magnesium on the latency of NMDA-induced convulsions; this effect is similar to
      that seen after administration of the dizocilpine (MK-801) channel blocker. An
      anticonvulsant effect of Mg2+ treatment is also observed with strychnine-induced
      convulsions but not with bicuculline-, picrotoxin-, or pentylenetetrazol-induced
      convulsions. In the forced swimming test, Mg2+ salts reduce the immobility time
      in a way similar to imipramine and thus resemble the antidepressant-like activity
      of MK-801. This activity is masked at high doses of magnesium by a myorelaxant
      effect that is comparable to MK-801-induced ataxia. Potentiation of yohimbine
      fatal toxicity is another test commonly used to evaluate putative antidepressant
      drugs. Administration of Mg2+ salts, like administration of imipramine strongly
      potentiates yohimbine lethality in contrast to MK-801, which is only poorly
      active in this test. Neither Mg2+ nor MK-801 treatment can prevent reserpine
      induced hypothermia. These data demonstrate that oral administration of magnesium
      to normal animals can antagonize NMDA-mediated responses and lead to
      antidepressant-like effects that are comparable to those of MK-801. This
      important regulatory role of Mg2+ in the central nervous system needs further
      investigation to evaluate the potential therapeutic advantages of magnesium
      supplementation in psychiatric disorders.

PMID- 9264102
TI  - Changes in tonic immobility and the GABA-benzodiazepine system in response to
      handling in the chick.
AB  - Changes in the GABA-benzodiazepine system were investigated following regular
      handling of male chicks. Compared with handling-naive chicks, those exposed to 10
      days of gentle handling required a larger number of inductions and had a lower
      duration of tonic immobility. Corresponding biochemical changes occurred, with
      handling-habituated chicks having a significantly lower basal [14C]GABA release
      from archistriatal slices and a reduction in the Bmax of [3H]muscimol binding in
      the forebrain. Benzodiazepine binding in the archistriatum was investigated using
      in vitro quantitative receptor autoradiography. Binding was localised in the
      anterior, mediale, dorsalis, and ventralis intermedium nuclei of the
      archistriatum, and there was significantly more binding in the anterior and
      ventralis intermedium/mediale archistriatum nuclei than in the dorsalis
      intermedium archistriatum nuclei. Benzodiazepine binding was not altered after
      handling in any of the investigated nuclei of the archistriatum. The results
      suggest that whereas several days of gentle handling in chicks leads to a
      decrease in forebrain GABAA receptors and a decrease in GABA release from the
      archistriatum, there are no accompanying changes in benzodiazepine receptors.
      Regular handling exerts a specific effect on chicks: it reduces their fear or
      human beings but not that of novel places or objects. It is possible that the
      pattern of biochemical changes observed in the present study may be specifically
      associated with this particular behavioural modification rather than with a
      change in general fearfulness.

PMID- 9264103
TI  - Involvement of opioid mu 1 receptors in morphine-induced conditioned place
      preference in rats.
AB  - The main purpose of this study was to evaluate the role of mu 1-opioid receptors
      in morphine reward. Therefore, we studied the ability of a mu 1-selective
      antagonist, naloxonazine [15 mg/kg intraperitoneally (IP)], to antagonize the
      conditioned place preference (CPP) induced by morphine [3 mg/kg subcutaneously
      (SC)]. In addition, effects of naloxonazine on morphine-induced catalepsy (15
      mg/kg), analgesia (3 mg/kg), and hyperthermia (3 mg/kg) were studied. For
      comparison, the effects of a nonselective opioid receptor antagonist, naltrexone
      (2.5 mg/kg SC), and a selective delta-opioid receptor antagonist, naltrindole (2
      mg/kg IP), on CPP induced by morphine were investigated. Morphine-induced CPP was
      clearly antagonized by pretreatment with naloxonazine and naltrexone (12 h and 20
      min prior to morphine, respectively) but not by naltrindole (15 min before
      morphine). Naloxonazine also antagonized morphine-induced catalepsy and analgesia
      but not morphine-induced hyperthermia. Naltrindole did not modify morphine
      induced catalepsy. These results suggest an active role for mu 1-opioid receptors
      in morphine reward, whereas morphine-induced hyperthermia does not appear to be
      mediated by mu 1-opioid receptors. Furthermore, delta-opioid receptors seem to be
      without significance in morphine-induced reward.

PMID- 9264104
TI  - Anticonvulsant activity of azirino[1,2-d][1,4]benzodiazepines and related 1,4
      benzodiazepines in mice.
AB  - The anticonvulsant properties of several 1,4-benzodiazepine and azirino[1,2
      d][1,4]benzodiazepine (ABDZ) derivatives were studied after intraperitoneal (IP)
      administration in DBA/2 mice (a strain genetically susceptible to sound-induced
      seizures) and in Swiss mice. The anticonvulsant effects were evaluated on
      seizures evoked by means of auditory stimulation (109 dB, 12-16 kHz) in animals
      placed singly under a hemispheric Perspex dome or on seizures induced by
      administration of pentylenetetrazole. The 1,4-benzodiazepines were generally more
      potent than the related ABDZ derivatives. The rank order of potency for
      anticonvulsant activity was flunitrazepam > diazepam > pinazepam > ABDZ5 > ABDZ4
      > prazepam > halazepam > ABDZ1 > ABDZ3 > camazepam > ABDZ6 > ABDZ2. The
      impairment of locomotor performance following IP administration of these
      derivatives was also evaluated by means of the rotarod test. The rank order of
      potency for impairment of coordinated motor movements was pinazepam >
      flunitrazepam > diazepam > ABDZ5 > prazepam > halazepam > ABDZ4 > ABDZ3 > ABDZ1 >
      camazepam > ABDZ2 = ABDZ6. The potency of various 1,4-benzodiazepines and ABDZs
      as inhibitors of specific [3H]flumazenil binding to membranes from cerebellum or
      cortex was evaluated. In general, ABDZs were active as anticonvulsants and
      inhibited [3H]flumazenil binding in the micromolar range. Radioligand binding
      studies carried out in stable cell lines demonstrated that none of the ABDZs
      tested showed a particular subtype specificity. The pharmacological actions of
      ABDZ4 and ABDZ5, which appeared to be the most potent ABDZs as anticonvulsants,
      were significantly reduced by treatment with flumazenil (8.24 mumol/kg IP),
      suggesting a clear involvement of benzodiazepine mechanisms in the anticonvulsant
      activity of these compounds or their metabolites. The anticonvulsant activity of
      ABDZ4 and ABDZ5 was also evaluated against seizures induced in DBA/2 mice by two
      beta-carbolines: methyl-beta-carboline-3-carboxylate (beta-CCM) and methyl-6,6
      dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM). Both ABDZ4 and ABDZ5 give
      better protection against seizures induced by beta-CCM than DMCM, suggesting a
      preferential action on the benzodiazepine receptor subtype BDZ1.

PMID- 9264105
TI  - Limits and limitations to nitrogen use in farm animals.

PMID- 9264106
TI  - Nitrogen metabolism in gastrointestinal tissue of the pig.

PMID- 9264108
TI  - Nutrient-hormone signals regulating muscle protein turnover in pigs.

PMID- 9264107
TI  - Regulation of hepatic nitrogen metabolism in ruminants.

PMID- 9264109
TI  - Nutritional control of amino acid supply to the mammary gland during lactation in
      the pig.
AB  - The paucity of data relating to lactation physiology of the sow has frustrated
      researchers in estimating nutrient needs for production and mammary maintenance
      functions. The nutritional control of amino acid supply for milk synthesis is
      influenced by factors that have yet to be measured, such as blood flow and amino
      acid contribution from the body protein pool. The interaction or role of hormones
      such as insulin, glucagon or prolactin in amino acid dynamics and inter-organ
      exchange during lactation in the sow, are not well understood. The discrepancy
      existing between milk and mammary amino acid uptake profiles relative to lysine
      may be indicative of mammary metabolism and possibly maintenance requirements for
      specific amino acids. Hence, amino acid metabolism in the mammary gland,
      regardless of arterial blood substrate supply, may play an important role in a
      factorial approach to determining requirements. Mammary amino acid uptake ratios
      rather than milk amino acid ratios should provide a better tool to estimate amino
      acid requirements relative to lysine. Although lysine has typically been limiting
      in maize-soyabean-meal-based diets fed to lactating sows, current production
      trends are bringing a new dimension to the formulation of lactating-sow diets.
      Other amino acids may become limiting if dietary crystalline lysine is added
      without concern for the whole essential amino acid profile. Formulations based on
      an ideal amino acid profile for the lactating sow will, therefore, become
      critical.

PMID- 9264110
TI  - Amino acid supply and metabolism by the ruminant mammary gland.

PMID- 9264111
TI  - Molecular mechanisms involved in the nutritional and hormonal regulation of
      growth in pigs.

PMID- 9264112
TI  - Immunological manipulation of growth.

PMID- 9264113
TI  - Modelling post-absorptive protein and amino acid metabolism in the ruminant.

PMID- 9264114
TI  - Mathematical modelling of nitrogen flow in growing pigs and lactating sows.
AB  - The present paper describes both nutrient-partitioning and metabolic models as
      applied to pigs. It is suggested that nutrient-partitioning models are most
      useful for use as management aids for commercial pork production, but that
      metabolic models may be more useful in understanding biological mechanisms. There
      is a pressing need for more quantitative information on potential protein
      deposition rates, the relationship between protein deposition and energy intake,
      endogenous amino acid losses, and metabolic effects on reproduction, all under
      varying conditions of genetic strain, health, ambient temperature, stocking
      density, and other factors.

PMID- 9264115
TI  - Postprandial lipid metabolism: an overview.

PMID- 9264116
TI  - Triacylglycerol and coronary heart disease.
AB  - Based on meta-analysis of prospective studies from the epidemiological
      literature, TAG is a risk factor for CVD, independent of HDL-cholesterol. The RR
      values were 1.3 and 1.8 for a 1 mmol/l increase in TAG among men and women
      respectively. Adjustment for HDL-cholesterol and other risk factors attenuated
      these estimates, but they remained statistically significant. Recent prospective
      findings from the Stanford Five City Project (Gardner et al. 1996) and the
      Physicians' Health Study (Stampfer et al. 1996) further demonstrate that TAG and
      LDL size are highly inter-related risk factors for CHD. Quantitative genetic
      analysis from large-scale family studies show that these correlations reflect
      common genetic influences that may be important for understanding genetic
      susceptibility to CHD.

PMID- 9264117
TI  - Postprandial lipid metabolism in relation to coronary heart disease.

PMID- 9264118
TI  - Postprandial lipid metabolism: effects of dietary fatty acids.

PMID- 9264119
TI  - Low-density lipoprotein subclasses: mechanisms of formation and modulation.

PMID- 9264120
TI  - The acylation-stimulating protein pathway and regulation of postprandial
      metabolism.
AB  - Much has recently been learned about the processes involved in postprandial
      triacylglycerol clearance. As discussed previously, important differences in the
      metabolism of chylomicrons and VLDL have become apparent. The ASP pathway has
      also been recognized and appears to play a critical role in chylomicron
      metabolism. The ASP pathway is activated in order to trap the fatty acids
      released from chylomicrons by the action of LPL and there is now unequivocal in
      vivo evidence in human subjects that ASP is generated by adipocytes in the
      postprandial period. These findings match the in vitro data showing that
      chylomicrons, but not the other plasma lipoproteins or fatty acids, activate the
      generation of ASP by cultured human adipocytes. An inverse relationship appears
      to exist between the proportion of fatty acids taken up by adipocytes and that
      released into the general circulation. Too great a release into the general
      circulation because of diminished trapping of fatty acids released from
      chylomicrons appears to be critical in the pathogenesis of the
      dyslipoproteinaemias associated with hyperapo B or FCHL and omental obesity.
      Evidence has been presented that dysfunction of the ASP pathway may be one of the
      causes of this disorder. Put differently, the ASP pathway is essential for the
      normal clearance and disposition of dietary fatty acids. Binding of chylomicrons
      to capillary endothelium followed by lipolysis by LPL results in the sudden
      liberation of fatty acids, and in the marked generation of ASP by adipocytes. The
      ASP that is generated is essential if LPL is to continue to form fatty acids at a
      normal rate. It is essential also if the fatty acids which are formed are to
      enter the adipocyte rather than exit into the general circulation. The transport
      vehicle, the chylomicron, therefore stimulates the formation of the peptide, ASP,
      which is responsible for its successful metabolism. Thus, the ASP pathway
      provides the metabolic coordination between the chylomicron and the adipocyte,
      which we describe as microenvironmental metabolic regulation and which we believe
      is essential for the normal clearance of dietary triacylglycerol from plasma.

PMID- 9264121
TI  - Regulation of the plasma non-esterified fatty acid concentration in the
      postprandial state.

PMID- 9264122
TI  - Lipoprotein lipase: regulation and role in lipoprotein metabolism.

PMID- 9264124
TI  - Postprandial lipid metabolism and thrombosis.

PMID- 9264123
TI  - Lipoprotein lipase (EC 3.1.1.34) targeting of lipoproteins to receptors.
AB  - Summarizing all available data on the role of lipases in targeting lipoproteins
      to their receptors, we propose the following model: TRL after hydrolysis by LPL
      have apo E exposed on their surface and might contain one or more molecules of
      LPL. Both 'apolipoproteins' direct the particles to the cell surface by high
      affinity binding to cellular proteoglycans. HL, bound to the surface of
      hepatocytes can further hydrolyse the particles and together with apo E and LPL
      mediate the binding to cellular receptors. The most important receptors
      recognizing these remnants are LRP and VLDLR. The LRP seems to be mainly
      responsible for the hepatic uptake of remnant lipoproteins, while the VLDLR,
      mainly located in adipose tissue and muscle, might target the lipoproteins to
      these tissues for fatty acid delivery.

PMID- 9264125
TI  - Effects of drugs on postprandial lipoprotein metabolism.

PMID- 9264126
TI  - Insulin action and non-esterified fatty acids. The European Group for the Study
      of Insulin Resistance (EGIR).

PMID- 9264127
TI  - Sir David Cuthbertson Medal Lecture. Energy metabolism in cancer and human
      immunodeficiency virus infection.

PMID- 9264128
TI  - Isolation of a novel cancer cachectic factor.

PMID- 9264129
TI  - Wasting illness as a disorder of body weight regulation.
AB  - Recent major breakthroughs in our understanding of the negative feedback control
      of body weight have modified our understanding of disorders characterized by both
      too much and too little body fat. On the one hand, defective negative feedback
      signalling in the form of leptin contributes to certain forms of obesity, at
      least in rodent models. On the other, excessive leptin-like signalling,
      potentially resulting from the elaboration of inflammatory cytokines, may
      contribute to the pathogenesis of wasting illness. With the rapid pace of
      progress that has occurred in this field in recent years, it seems likely that
      breakthroughs in the treatment of these catastrophic illnesses may follow in the
      wake of new insights into the physiology and pathophysiology of body weight
      regulation.

PMID- 9264130
TI  - Measurement of muscle proteolysis and the impact on muscle wasting.

PMID- 9264131
TI  - Liver protein and glutamine metabolism during cachexia.

PMID- 9264132
TI  - Susceptibility loci for bipolar affective disorder on chromosome 18? A review and
      a study of Danish families.
AB  - Chromosome 18 is one of the most promising chromosomes in the search for
      susceptibility genes for bipolar disorder based on results from cytogenetic,
      linkage, and association studies. Susceptibility loci on chromosome 18p and 18q
      have been suggested for bipolar affective disorder. We present a review of
      published studies which suggests that it is presently unclear whether one or more
      susceptibility loci on chromosome 18 exist, and that their more accurate
      localization is unknown. The present study investigated 27 DNA markers on
      chromosome 18 in two Danish families with bipolar affective disorder. We found
      positive lod scores in the larger family for markers on chromosome 18q12,
      especially for the affection status model which only includes bipolar patients.
      The highest lod score found was for marker D18S67, 1.83 at 0.05 recombination
      fraction.

PMID- 9264133
TI  - Lack of association of catechol-O-methyltransferase (COMT) functional
      polymorphism in bipolar affective disorder.
AB  - Abnormal catecholamine transmission has been implicated in the pathogenesis of
      mood disorders. Consequently, alterations in genes that are involved in
      catecholamine metabolism could be potential candidates for bipolar affective
      disorder (BPD) vulnerability. One such candidate is catechol-O-methyltransferase
      (COMT). A functional polymorphism has recently been characterized that is
      responsible for substantial variability in COMT enzymatic activity. A relatively
      low activity allele is associated with a methionine residue at amino acid 158 of
      membrane bound COMT whereas a high activity variant has a valine at this site. We
      have now screened 63 unrelated patients with BPD for this functional
      polymorphism. However, no significant association was detected. This suggests
      that the codon 158 COMT polymorphism is not a susceptibility gene in BPD.

PMID- 9264134
TI  - Allelic association between D2 but not D1 dopamine receptor gene and alcoholism
      in Finland.
AB  - We studied the relationship of D2 and D1 receptor gene polymorphisms and
      alcoholism in male Finnish alcoholics and assessed male controls. Seventy
      alcoholics entering a detoxification programme and 50 control individuals were
      recruited. Forty-three per cent of the alcoholic patients, but only 22% of
      controls, had the D2 receptor gene TaqI A restriction fragment length
      polymorphism A1 allele. The frequency of the A1 allele was significantly higher
      in alcoholics (p = 0.039). In comparison, no association between alcoholism and
      the D1 receptor gene EcoRI restriction fragment length polymorphism alleles was
      found. A logistic regression analysis of the alcoholic population failed to
      support the idea that the presence of the A1 allele would be linked to estimates
      of alcohol dependence severity rated with the Severity of Alcohol Dependence
      Questionnaire or the Michigan Alcoholism Screening Test. In conclusion, allelic
      association between the D2 but not D1 receptor gene and alcoholism in a
      genetically relatively homogenous population of male Finns was found. The results
      are in agreement with the view that the D2 receptor locus is involved in genetic
      susceptibility to alcoholism but does not give support to a special association
      of severe alcohol dependence and the A1 allele of the D2 receptor gene.

PMID- 9264135
TI  - Age-of-onset or age-cohort changes in the lifetime occurrence of depression?
AB  - In a re-investigation of the NIMH Psychobiology of Depression data, we have
      studied the question of shifts towards earlier onset together with the question
      of steadily increasing lifetime risk of major depression in successive birth
      cohorts. Using a contingency-table approach, it turned out that inhomogeneities
      with respect to successive birth-cohorts exclusively showed up in the
      neighborhood of principally unobservable combinations of the variables under
      investigation. Standard approaches to testing independence in cross-classified
      data, such as the quasi-independence model, yielded highly significant results.
      Through the definition of a log-linear model with weights which replaces the
      'discrete' truncation of the quasi-independence approach by a 'smoothed'
      truncation, it was possible to fully explain the observed age-of-onset shifts,
      thus supporting the hypothesis that age-of-onset and birth-cohort are
      independent. With respect to the question of generational changes in the lifetime
      risk of depression this independence implied that such changes should occur at
      equal rates across all ages of onset. The analysis yielded significantly larger
      cohort sizes for the two youngest birth-cohorts, a fact which might be
      interpreted as an indication of increasing environmental impacts on the
      genetically predisposed vulnerability during recent years. However, our cross
      sectional survey data were, by design, not an optimal basis for a reliable
      assessment of changes in the lifetime risk of depression, because the risk
      estimate derived from affected-only survey data corresponds to the probability
      that a depressive belongs to a certain birth-cohort and is only loosely related
      to the lifetime risk of this cohort (which is the probability that a person
      belonging to a certain birth-cohort develops depression). We therefore conclude,
      firstly, that method effects are likely to explain a major portion of secular
      trends thus far reported in the literature, and, secondly, that there appears to
      be no clear necessity to include changing environmental effects into quantitative
      genetic modelling.

PMID- 9264136
TI  - Lack of allelic association between 102T/C polymorphism of serotonin receptor
      type 2A gene and schizophrenia in Chinese.
AB  - Recent studies have reported an association between a 102T/C polymorphism of
      serotonin receptor type 2A gene (5-HT2A) and schizophrenia. In addition, an
      association was detected between a 102T/C polymorphism of the 5-HT2A receptor
      gene and drug response to clozapine in the treatment of schizophrenic patients.
      These studies suggest an important role of the 5-HT2A gene in schizophrenia. To
      study the possible involvement of the 5-HT2A gene in the pathogenesis of
      schizophrenia, a case-control association study was carried out in a Chinese
      population from Taiwan. No significant differences of genotype distributions,
      allele frequencies and homozygosity were detected between schizophrenic patients
      (n = 177) and nonpsychiatric controls (n = 98). When subjects were divided into
      subgroups according to sex, still no differences of allele frequencies or
      genotype distributions were noted between patients and controls. Our data do not
      support an allelic association between the 102T/C polymorphism of the 5-HT2A
      receptor gene and schizophrenia in Chinese population.

PMID- 9264137
TI  - PCR amplification of the Taq I B1/B2 polymorphism at intron 5 of the dopamine
      beta-hydroxylase gene.

PMID- 9264138
TI  - Recurrent brief depression in Prader-Willi syndrome: a case report.
AB  - Prader-Willi syndrome is caused by a deletion of 15q11-13 or maternal disomy of
      chromosome 15. A female patient with Prader-Willi syndrome, who was 19 years of
      age at the first onset of her recurrent brief episodes, is described. The
      episodes showed a near-monthly rhythm and were followed by a spontaneous
      remission in 7-18 days. The symptoms during the episodes were anorexia, insomnia,
      guilt feelings, ideas of being doomed, ostracized and persecuted, and stupor
      alternating with agitation.

PMID- 9264139
TI  - Functional promoter polymorphism of the human serotonin transporter: lack of
      association with panic disorder.
AB  - To probe the hypothesis of a role for a functionally relevant 44 bp
      insertion/deletion of the serotonin transporter promoter in the aetiopathogenesis
      of panic disorder, we determined the allele frequency of the variant in two
      samples (combined n = 158) of panic disorder patients (DSMIII-R) and compared it
      with its allele frequency in two ethnically matched control samples (combined n =
      169). The fact that no difference could be observed (x 2 analysis) argues against
      a major role for this serotonin transporter promoter polymorphism in the
      aetiopathogenesis of panic disorder.

PMID- 9264140
TI  - Genes and manic depression.
AB  - Recent reports on susceptibility loci for manic depression have sparked lively
      debate. The pros and cons of these findings are discussed from a methodological
      vantage point, with implications for linkage studies generally.

PMID- 9264141
TI  - Cortisol, high cortisol diseases and anti-cortisol therapy.
AB  - Elevated cortisol is found in many diseases, including infectious, aging-related,
      depression and depression-associated conditions; even in some with no known
      origin, and no known therapy. While it was initially thought that 'high cortisol'
      is the result of these diseases, there is mounting evidence to the contrary,
      namely, that high cortisol actually plays a major role in inducing them, opening
      the possibility that anti-cortisol drugs might represent a new beneficial
      therapy. Evidence is here presented, showing that the use of anti-cortisol drugs
      has already induced beneficial results in conditions ranging from AIDS to
      depression. A main reason for not realizing the major role played by cortisol is
      due to a defective interpretation of cortisol results. If cortisol is within
      normal range of 0800 h or 1700 h, it has been considered normal, without
      realizing that swings, sometimes at immunosuppressive levels, might occur during
      its 24 h circadian rhythm. We suggest that a first step toward unveiling the role
      of cortisol in diseases would be to develop a standardized cortisol circadian
      rhythm chart that would show normal levels at any time during a 24 h period,
      enabling a more accurate comparison with cortisol values obtained under
      pathological conditions.

PMID- 9264142
TI  - Serum cortisol and DHEA concentrations during HIV infection.
AB  - The progression of HIV infection is accompanied by severe immunodepression and
      cachexia, particularly during advanced stages. The immune depression is due
      largely to a dramatic drop in the number of CD4 cells. The loss of body weight is
      mainly due to a reduced fat-free mass with no change in adipose tissue. We
      determined the serum concentrations of cortisol and DHEA and their correlations
      with absolute CD4 cell counts and changes in body weight of HIV-positive men. The
      results of five retrospective and prospective studies indicate that the serum
      concentrations of cortisol and DHEA in HIV-infected patients were different from
      those of HIV-negative controls. Serum cortisol was elevated at all stages of
      infection (+20 to +50%, p < .05 to p < .001) particularly in AIDS patients (stage
      IV C). In contrast, the serum DHEA concentrations were closely correlated with
      the stage of HIV-infection, being higher in the early stages (stages II and III
      or > 500 CD4) than in advanced stages (IV C or < 500 CD4)-in the latter being
      below those of HIV-negative men-or in controls (+40 to 100%, p < .01 to p <
      .001). There was a negative linear correlation between the CD4 cell counts and
      cortisol (r = -0.4, p < .02) and a positive linear correlation with DHEA (r =
      +0.36, p < .01). There was no significant correlation between delta body weight
      and serum cortisol. In contrast, there was a negative correlation between serum
      DHEA and delta body weight (%) (r = -0.69, p < .0001) and a positive correlation
      with the cortisol/DHEA ratio (r = +0.61, p < .0001). There is thus a link between
      the circulating concentrations of adrenal steroids and the progression of
      immunosuppression and cachexia during HIV-infection. This raises the question of
      whether there is a cause-and-effect relationship between clinical progression and
      circulating steroid concentrations. Further investigations into the relationship
      between the ratio cortisol/DHEA and the immune response and cachexia should
      indicate the contributions of these steroids to the etiology of HIV infection and
      lead to the development of new therapeutic strategies.

PMID- 9264143
TI  - Glucocorticoids and the immune system in AIDS.
AB  - An interesting aspect of HIV disease is the immunoendocrine dialogue, via the
      hypothalamo-pituitary-adrenal axis, between glucocorticoids and cytokines and its
      potential role in HIV disease progression. This study reports recent data on the
      interaction between glucocorticoids and the immune system in AIDS patients with
      an acquired form of glucocorticoid resistance. Clinically, glucocorticoid
      resistant AIDS patients (AIDS-GR; about 12% in our series of patients) present
      Addisonian symptoms (weakness, weight loss, hypotension, hyponatremia and intense
      mucocutaneous melanosis) in spite of elevated values of plasma cortisol and
      urinary free cortisol. Monocytes from these patients have a significantly lower
      receptor affinity (higher Kd) for glucocorticoids and a higher receptor density
      than other patients and controls. Such receptor alteration is associated with
      higher values of plasma interferon alpha (IFN alpha). In AIDS-GR there is a
      significant correlation between the values of receptor Kd and of plasma IFN alpha
      (r = 0.77). After poly(I):poly(C) stimulation, monocytes from AIDS-GR produce
      much more IFN alpha than other AIDS patients. While in patients with no
      resistance and in control patients, monocyte production of IFN alpha is inhibited
      by dexamethasone (the effect being reversed by RU-486), a very slight inhibition
      of dexamethasone on IFN alpha production is observed in monocytes from AIDS-GR.
      In conclusion, these data demonstrate that the immunosuppressive mechanisms
      acting in AIDS may be reversed, as shown by the increased stimulus on IFN alpha
      production found in cortisol-resistant patients. These data also suggest that
      antiglucocorticoid drugs may be helpful in HIV disease as they antagonize the
      excessive immunosuppression induced by the increased production of
      glucocorticoids found at every stage of HIV disease.

PMID- 9264145
TI  - Programmed cell death in HIV infection: dysregulation of BCL-2 and Fas pathways
      and contribution to AIDS pathogenesis.
AB  - In the peripheral immune system, apoptosis is involved in the down-regulation of
      immune reactions, acting as a homeostatic mechanism to limit the expansion of
      activated lymphocytes, for example in viral diseases. We previously reported that
      uninfected T lymphocytes from HIV-infected persons were highly prone to in vitro
      spontaneous apoptosis which was increased following TCR-dependent or independent
      activation. The present report reviews recent data suggesting that the chronic
      stimulation of the immune system in HIV infection induces a dysregulation in the
      expression of molecules involved in cell survival (Bcl-2) or cell death (Fas),
      promoting an exacerbated peripheral cell death in blood and lymph nodes, possibly
      contributing to the loss of both functional cytotoxic and helper T lymphocytes in
      AIDS.

PMID- 9264144
TI  - A possible role for the cortisol/anticortisols imbalance in the progression of
      human immunodeficiency virus.
AB  - The progression of HIV infection is accompanied by complex alterations in the
      production of adrenal steroids. Cortisol levels are increased in HIV infection
      whereas those of dehydroepiandrosterone (DHEA), a physiologic antagonist of the
      immunoregulatory activities of cortisol, decrease. The progression of HIV
      infection to AIDS is also characterised by a shift from a type 1 to type 2
      cytokine production. Thus, defective production of interferon gamma (IFN gamma),
      interleukin (IL)-2, and IL-12 as well as increased production of IL-4, IL-5, IL
      6, and IL-10 are observed in HIV-seropositive individuals and are proposed to be
      in vitro immunologic marker of progression. Cortisol and pharmacological doses of
      glucocorticoids (GC) suppress IL-2 and IFN gamma production and favour the
      production of IL-4. Furthermore, GC and IL-4 stimulate the differentiation of B
      lymphocytes into IgE producing plasma cells, the concentration of which augments
      in HIV infection. Finally, GC induce programmed cell death (PCD) in a variety of
      different cells, including mature T lymphocytes, and type 2 cytokines were
      recently proposed to augment the susceptibility of T lymphocytes to PCD. It was
      suggested that the progressive shift from type 1 to type 2 cytokine production
      characteristic of HIV infection could be at least partially provoked by the
      increase in the production of cortisol and the reduction of DHEA. This hypothesis
      is discussed within the scenario of an endrocrinologic imbalance being
      responsible for HIV progression at least partially via increased susceptibility
      of HIV + CD4 lymphocyte to PCD.

PMID- 9264146
TI  - HIV-1 viral protein R (Vpr) as a regulator of the target cell.
AB  - Among the putative 'accessory genes' of HIV-1, the 96 amino acid virion
      associated Vpr gene product has been described to have several novel biological
      activities. These include cytoplasmic-to-nuclear translocation thus empowering
      HIV to infect and replicate in nondividing cells and to function to increase
      viral replication, particularly in monocytes. Along with these viral effects, we
      describe the dramatic biological changes induced by HIV-1 Vpr in the target cells
      of HIV infection including induction of changes in transcriptional patterns and
      complete inhibition of proliferation which collectively is termed
      differentiation. These changes occur in the absence of other viral gene products
      and suggest that Vpr mediates its proviral effects partially or perhaps solely
      through modulation of the state of the target cell rather than directly on the
      virus. The inhibition of proliferation in T-cell lines has been proposed by
      several groups to demonstrate that the inhibition of proliferation specifically
      arrests the cell cycle further supporting the notion that Vpr activity is
      directed at cellular targets. We have recently described a role for Vpr in
      modulating the glucocorticoid pathway, a pathway involved in the regulation of
      the state of the cell in cytoplasmic-to-nuclear translocation and in the
      modulation of host cell transcription. Importantly, certain antiglucocorticoids
      have been shown to modulate Vpr activity in vitro. These results demonstrate that
      the cell contains specific receptor(s) molecule(s) through which Vpr mediates its
      activity and that these molecules have implications for cell biology in general.
      These results collectively demonstrate that Vpr represents a unique target for
      anti-HIV drug development and has significance for HIV-1 disease progression.

PMID- 9264148
TI  - The effect of dehydroepiandrosterone (DHEA) on Zucker rat food selection and
      hypothalamic neurotransmitters.
AB  - The effect of dehydroepiandrosterone (DHEA) administered as an acute
      intraperitoneal (IP) injection on food selection and levels of hypothalamic
      neurotransmitters of obese Zucker rats was investigated. Animals consumed a
      'macronutrient selection' diet which consisted of three separate foodstuffs; they
      were nearly pure selections of fat, protein or carbohydrate. On the day before
      DHEA treatment, food bowls were removed at 1700 h and the animals fasted. The
      next morning some were treated with IP DHEA (100-200 mg/kg) while the controls
      received vehicle. Two hours later, their food intakes over 4 h were quantitated
      or, in other experiments, the animals were decapitated and hypothalamic
      neurotransmitter levels determined. Results showed that the administration of
      DHEA clearly diminished the amount of fat the animals consumed while their
      intakes of carbohydrate and protein were unchanged. Levels of neurotransmitters
      in the paraventricular nuclear region were altered. It is concluded that DHEA
      diminishes the fat food consumption of obese Zucker rats by altering the levels
      of neurotransmitters in select regions of the hypothalamus.

PMID- 9264147
TI  - Pituitary-adrenal response to RU 486 in man.
AB  - New therapeutic indications of the antiprogesterone RU 486 are emerging which
      require long-term administration and raise the question of its safety because of
      the associated antiglucocorticoid action of the drug. A trial was designed to
      assess the antiglucocorticoid effect of RU 486, possible manifestations of
      peripheral cortisol deprivation, and the adrenocortical and corticotrophin
      reserves. Ten normal males were given RU 486 per os (200 mg/day) or placebo
      between 0800-0900 h for eight days in a randomized, double-blind, crossover
      design, with a 1-month interval between the two periods. RU 486 induced the
      overactivation of the pituitary-adrenal axis. Baseline values (mean +/- SEM)
      before and at end of treatment were, respectively: 0800 h plasma cortisol, 147.3
      +/- 15.5 and 257.6 +/- 8.8 ng/ml; 0800 h salivary cortisol, 5.8 +/- 1.2 and 15.2
      +/- 0.8 ng/ml; nocturnal (2200-0800 h) urinary cortisol, 8.4 +/- 1.5 and 33.7 +/-
      11.1 micrograms; and 0800 h plasma ACTH, 29.2 +/- 3.7 and 60.2 +/- 8.4 pg/ml. All
      of these variations were different from those during placebo treatment (0.0001 <
      p < .03) and disappeared four days after the end of treatment. A daily record of
      subjective clinical symptoms, body weight and temperature, blood pressure, and
      heart rate showed no side effects, and no significant variation during treatment.
      Blood electrolyte and eosinophil counts were unchanged; fasting blood glucose was
      slightly higher at the end of treatment (5.0 +/- 0.2 vs. 4.7 +/- 0.1 mmol/L; p <
      .04). The adrenocortical response to Cortrosyn (0.25 mg IM) was exaggerated
      during RU 486 treatment (p < .006). Peak values before and at the end of
      treatment were, respectively: plasma cortisol, 272.5 +/- 15.2 and 347.1 +/- 20.6
      ng/ml; and salivary cortisol, 17.0 +/- 2.2 and 31.1 +/- 3.1 ng/ml. Direct
      pituitary stimulation (100 micrograms ovine corticotrophin release hormone (CRH),
      followed by 1 IU LVP) also induced exaggerated corticotroph and adrenocortical
      responses (p < .005). Peak values before and at the end of treatment were,
      respectively: plasma ACTH, 147.7 +/- 24.6 and 254.0 +/- 41.3 pg/ml: and plasma
      cortisol, 231.6 +/- 7.3 and 319.2 +/- 12.3 ng/ml. These data show that 8-day
      treatment with 200 mg RU 486 daily induces a hormonally detectable
      antiglucocorticoid effect without clinical symptoms. This state results in a
      reversible cortisol overproduction and a preservation of adrenocortical and
      pituitary reserves.

PMID- 9264149
TI  - HPA axis dysfunction in depression: correlation with monoamine system
      abnormalities.
AB  - Abnormality of the hypothalamic-pituitary-adrenal (HPA) axis has been one of the
      most consistently demonstrated biological markers of depressive disorder. It has
      also been proposed that abnormality of monoamine function plays a role in the
      pathogenesis of the disorder. In order to examine the interrelationships of the
      HPA axis with the dopaminergic, noradrenergic, and serotoninergic systems, we
      studied, in 52 medication-free inpatients with DSM-IV nonpsychotic major
      depressive disorder, the relationship between dexamethasone suppression test
      (DST) status and a series of multihormonal responses to apomorphine (APO),
      clonidine (CLO), and D-fenfluramine (FEN) tests. DST nonsuppressors did not
      present any difference compared with suppressors in growth hormone (GH) and
      cortisol stimulation by APO suggesting that a chronic elevation of cortisol did
      not lead to an alteration of dopaminergic activity in this population of
      nonpsychotic depressed inpatients. Cortisol and prolactin responses to FEN were
      comparable in nonsuppressors and in suppressors. In contrast, GH response to CLO
      was lower in DST nonsuppressors than in suppressors (p < .03), suggesting that
      the HPA abnormality indicated by a positive DST may be related to alpha 2
      adrenoreceptor dysfunction.

PMID- 9264150
TI  - Synaptic functions in the aged rat hippocampus: a target for corticosteroids?
AB  - The role of corticosteroids in brain aging remains a controversial issue.
      Conceivably, if corticosteroids levels are increased in the aged brain, neuronal
      function might be altered. For instance, GABA-mediated synaptic events, spike
      accommodation and afterhyperpolarizing potentials (AHPs) might be modified. Our
      electrophysiological results show that the most consistent alterations observed
      in the aged rat hippocampus concern cholinergic receptors, glutamatergic NMDA
      receptors and GABAB receptors mediated synaptic potentials. In contrast no
      consistent alterations were observed in afterhyperpolarizing potentials, calcium
      spikes, or GABAA mediated synaptic events. Therefore our electrophysiological
      results are difficult to reconcile with a 'glucocorticoid cascade hypothesis,'
      involving an elevated level of corticosterone in the aged rat.

PMID- 9264151
TI  - Regulation of cytokine gene expression in the central nervous system by
      glucocorticoids: mechanisms and functional consequences.
AB  - The proinflammatory cytokines which are released by activated accessory immune
      cells during the course of an infection have profound effects on the brain. These
      effects include activation of the hypothalamic-pituitary-adrenal axis, fever and
      behavioral depression. They are mediated by cytokines which are synthesized and
      released in the brain, in response to peripherally released cytokines.
      Glucocorticoids have potent regulatory effects on the synthesis of cytokines by
      activated macrophages and monocytes. These hormones are also able to regulate the
      synthesis and action of cytokines in the brain, as demonstrated by the
      sensitizing effects of adrenalectomy and the depressing effects of stress on the
      increased cytokine and interleukin-1 beta converting enzyme gene expression that
      occurs in response to lipopolysaccharide in mice. Preliminary experiments
      indicate that another way glucocorticoids can contribute to down regulation of
      the IL-1 system is by increasing the expression of the type II IL-1 receptor in
      the brain. The regulatory effects of glucocorticoids on cytokine expression in
      the brain have functional consequences, as demonstrated by the enhanced
      sensitivity of adrenalectomized animals to the behavioral actions of centrally
      administered LPS and IL-1. The effects of adrenalectomy are inhibited by
      compensation with a corticosterone implant and they are mimicked by
      administration of the type II glucocorticoid receptor, RU 38486. The regulatory
      role of glucocorticoids on the expression and action of cytokines in the brain
      makes these hormones and their mechanisms of action key targets for therapeutic
      interventions in psychopathology and neuropathology.

PMID- 9264152
TI  - Corticosteroid effects on electrical properties of brain cells: temporal aspects
      and role of antiglucocorticoids.
AB  - Pyramidal cells in the CA1 hippocampal area express both mineralo- and
      glucocorticoid receptors (MRs and GRs respectively) to which the rat adrenal
      hormone corticosterone binds effectively. Through activation of these receptors
      corticosteroids exert a delayed and persistent control over signal transduction
      in the hippocampus. Many cellular responses are affected by the hormone,
      including responsiveness to serotonin (5HT) and the cholinergic agent carbachol
      (CCh). It was found that predominant MR occupation results within hours in small
      responses to 5HT and to CCh. Concomitant activation of GRs leads to larger
      transmitter responses. Particularly strong responses to 5HT were observed 1-4
      hours after an acute stress; this could be prevented by pretreatment with the
      antiglucocorticoid RU38486. Steroids also exert a long-term effect on aminergic
      responses. Chronic exposure to a very high corticosterone dose was found to
      depress 5HT responses. These data indicate that short-term fluctuations in
      corticosterone level alter neurotransmitter responses in the hippocampus, a
      structure involved in mood and cognition. In addition, long-term aberrations in
      corticosteroid levels, e.g. due to glucocorticoid feedback resistance in
      association with several stress-related disorders, also change the hippocampal
      responsiveness to monoamines. Future studies will have to examine the potential
      of antiglucocorticoids to restore this disturbed neurotransmitter function.

PMID- 9264153
TI  - Behavioral and neuroendocrine responses controlled by the concerted action of
      central mineralocorticoid (MRS) and glucocorticoid receptors (GRS).
AB  - The balance between MR- and GR-mediated effects is of paramount importance for
      the homeostatic control of stress responsiveness, adaptation and cognition in
      animals. If the MR/GR activation ratio is shifted, the control of glucocorticoids
      on neuronal excitability (Joels & de Kloet, 1994), neuroendocrine reactivity and
      behavior will change (de Kloet, 1991). In order to elucidate the underlying
      neural substrate of behavior, the different levels of biological organization
      must be brought into relation with each other. For instance, we have suggested
      that GRs are involved in the storage of information and MRs in the execution of
      behavior preceding information processing. It is nevertheless important to
      reemphasize that the biological significance of behavioral responses is due to
      the concerted action of various receptor systems. In addition, the results on the
      function of MRs and GRs show clearly that the coupling of one receptor with one
      function is too reductionistic to fully explain the biological relevance of such
      receptors.

PMID- 9264154
TI  - What are ago-antagonistic couples? Their role in normal and pathological
      situations. Therapeutical consequences.
AB  - Two classes of steroid hormones are successively produced following a microbial
      infection stress in rat and man. First there are those of attenuation and
      acceptation, the glucocorticoids and progestins, which correspond to the
      temporization phase of reaction to stress. Secondly, there are those of rejection
      or creative reinforcement, namely the adrenal androgens converted in certain
      circumstances to estrogens by aromatization, which are necessary to fight against
      or accept the stressor. We suggest that these two classes of signal carrier
      molecules function as agonistic-antagonistic couples which work to prevent the
      organism from going too far in the direction of attenuation-acceptation or, on
      the contrary, in the direction of rejection-reinforcement. The presence of
      agonistic-antagonistic couples can be identified as regulating numerous other
      steps in the signal networks. Dysfunctions of such couples result in pathological
      situations, characterized by an imbalance in the concentration and
      correspondingly in the biological activity of one of the partners due to a change
      in the 'equilibrium constant' of the ago-antagonistic couple, changes in the
      level of synthesis or catabolism of one of the partners, the presence in adequate
      time and location of the partners, or the deficiency of the receptor of at least
      one of the partners. Different 'paradoxical' therapeutical strategies are
      envisaged to reequilibrate the imbalance.

PMID- 9264155
TI  - Antiglucocorticoid function of androstenetriol.
AB  - The anti-inflammatory and immunosuppressive functions of corticosteroids have
      been well established and characterized. In contrast, a different group of native
      steroids, which include dehydroepiandrosterone (DHEA) and two of its metabolites,
      androstenediol (5-androstene-3 beta-17 beta-diol, AED) and androstenetriol (5
      androstene-3 beta-7 beta-17 beta-triol, beta AET), function in vivo to up
      regulate host immune response against infections and counteract stress-induced
      immunosuppression. Indeed, DHEA and particularly, AED and beta AET, have been
      shown to protect mice from viral, bacterial, and parasitic infections. In vivo,
      these three hormones are in opposition to the widely demonstrated
      immunosuppressive action of glucocorticoids, suggesting a possible new immune
      regulation mechanism. The individual activity in vitro of each of these steroids,
      i.e. DHEA, AED, and beta AET, on a mitogen-induced mixed splenocyte proliferation
      assay were determined. The results showed that DHEA suppressed the proliferation
      of cultures activated with concanavalin A (ConA) or lipopolysaccharide (LPS) in a
      dose-dependent manner. AED had little influence on the activation response.
      However, beta AET potentiated the response to both mitogens significantly above
      control. The regulation of the cytokine secretion, of both interleukin-2 (IL-2)
      and interleukin-3 (IL-3), from ConA-activated lymphocytes was affected in the
      same manner. These functions were depressed by DHEA, unaffected by AED, and
      potently increased by beta AET. Moreover, the classic immunosuppressive effects
      of hydrocortisone on ConA-induced lymphocyte proliferation, as well as on IL-2
      and IL-3 production, were unaffected by being co-cultured with DHEA and only
      minimally counteracted by AED at high doses. In contrast, co-culturing with beta
      AET significantly counteracted the immunosuppressive effects of hydrocortisone on
      lymphocyte proliferation and cytokine production. These data show that in-vivo,
      DHEA, AED, and beta AET may have some similar functions, while in vitro, their
      effects are dramatically different from one another. Only beta AET could markedly
      potentiate the cellular response by increasing lymphocyte activation and
      counteracting the immnosuppressive activity of hydrocortisone on lymphocyte
      proliferation and cytokine production.

PMID- 9264156
TI  - Pathogenetic role, in human and murine tuberculosis, of changes in the peripheral
      metabolism of glucocorticoids and antiglucocorticoids.
AB  - Immunity to tuberculosis (TB) requires a Th1 pattern of cytokine release,
      dominated by interleukin-2 (IL-2) and interferon gamma (IFN gamma). In
      experimental models even a minor Th2 component (characterized by production of IL
      4) abrogates immunity, and leads to an immunopathology that mimics the human
      disease. Increased exposure of T cells to glucocorticoids drives them towards a
      Th2 cytokine profile and could therefore help to explain the presence of an
      inappropriate Th2 component in TB. Analysis of adrenal steroid metabolites in 24
      h urine collections revealed a striking increase in metabolites of active
      cortisol relative to metabolites of inactive cortisone. This indicates a change
      in the balance of 11 beta-hydroxysteroid dehydrogenase to 11 beta-ketosteroid
      reductase. The site of this disease-associated alteration in
      reductase/dehydrogenase balance may be the lung. The lung contains 11 beta HSD-1,
      (a reversible oxido-reductase) which in the liver works as a reductase. In the
      normal lung it functions paradoxically as a reductase, but it can alter its
      function in the presence of cytokines. TB patients (like other ill individuals)
      also show reduced 24-h urinary secretion of dehydroepiandrosterone (DHEA)
      derivatives. Since these have antiglucocorticoid functions in vivo, this fall may
      exacerbate the effects of the reduced inactivation of cortisol and loss of
      diurnal rhythm, and contribute to immunological dysfunction. Recent studies of TB
      in mice, and in children during infancy, adrenarche and puberty, suggest that the
      ratio of cortisol to DHEA may be crucial both to susceptibility and to the
      pathology of the disease that develops.

PMID- 9264157
TI  - The acute effect of a noontime meal on the serum levels of cortisol and DHEA in
      lean and obese women.
AB  - Lean [n = 11, body mass index (BMI) < 22.5] and obese (n = 13, BMI > 31.5) women
      consumed a noontime meal while serum levels of cortisol and
      dehydroepiandrosterone (DHEA) were measured. Before the meal the obese had lower
      levels of serum cortisol compared to the leans. Within 20-40 min of consuming the
      meal the levels of cortisol rose in both groups; those of the obese rose by a
      greater increment and in the first postprandial hour there were no differences
      between lean and obese. After the meal-induced peak, the obese again had lower
      cortisol values. DHEA levels rose with the meal in both groups but the difference
      over baseline was only significant for the obese. These results show that the
      lean and obese respond differently to the physiologic stimulus of a meal. These
      results are consistent with the hypothesis that obesity is influenced by
      differences in adrenal function that are demonstrable during stimulation with a
      meal.

PMID- 9264158
TI  - Antiglucocorticoid treatments in psychiatry.
AB  - A confluence of evidence indicates that alterations in hypothalamic-pituitary
      adrenal regulation can have profound effects on the symptom picture of
      psychiatric illnesses and that therapeutic interventions directly targeted at
      corticosteroid metabolism may have clinical benefit. This paper reviews the
      varying lines of inference that support such a hypothesis and reviews work by our
      group and others utilizing the cortisol synthesis inhibitor, ketoconazole and,
      more recently, dehydroepiandrosterone (DHEA), as potential novel mood-altering
      agents. The data thus far suggest that antiglucocorticoid drug treatment may be
      useful in certain subgroups of depressed patients and may offer a theoretical
      rationale for alternative drug design.

PMID- 9264159
TI  - Antiglucocorticoid therapies in major depression: a review.
AB  - In major depression there are two well-documented biochemical abnormalities:
      hypercortisolism, and its resistance to dexamethasone suppression. It therefore
      seems reasonable to see if giving drugs which interfere with cortisol
      biosynthesis might bring about a remission. An open trial was begun in our
      institution of 20 refractory patients with major depression. Aminoglutethimide,
      metyrapone, ketoconazole or combinations of these drugs along with a maintenance
      dose of cortisol were used for eight weeks. Of the 17 completers, eleven patients
      were considered to have good responses and two partial responses. Four had
      complete remissions lasting several years. A similar study of four patients who
      received oral RU 486 also gave encouraging results. Two patients with obsessive
      compulsive disorder associated with depression showed striking improvement on
      aminoglutethimide combined with a serotonin re-uptake inhibitor. In addition to a
      case report in 1988 by Ravaris et al. of a patient hypophysectomized for previous
      Cushing's syndrome whose depression responded to ketoconazole, several other
      studies over the past five years have had similar favorable results. Wolkowitz et
      al. (1993) gave oral ketoconazole to 10 depressed patients for three weeks which
      resulted in a significant drop in their Hamilton Depression Scale ratings.
      O'Dwyer et al. (1995) conducted a placebo-controlled single-blind crossover study
      using lifetyrapone and maintenance cortisol in eight inpatients for two weeks;
      six responded. Thakore and Dinan (1995) studied eight inpatients using
      ketoconazole for four weeks; there were five responders and three partial
      responders. Anand et al. (1995) conducted a four-week double-blind trial of
      ketoconazole in a single treatment-refractory patient with good results. Arana et
      al. (1995) used a different approach but one which also leads to suppression of
      endogenous corticosteroids-i.e. short-term dexamethasone suppression (4 mg/day
      for four days). When tested at 14 days, 7/19 of the dexamethasone group had
      responded well while only 1/18 of the placebo group had responded. While these
      studies have shortcomings, antiglucocorticoid therapy appears to be an effective
      tool in the treatment of major depression. Possible mechanisms are discussed, and
      a unifying hypothesis is attempted.

PMID- 9264160
TI  - Postoperative hyperamylasaemia in cardiac surgery.
AB  - The mechanism of postoperative hyperamylasaemia was studied in 48 patients
      undergoing coronary artery bypass grafting (CABG). Mild hyperamylasaemia
      developed in 87% of the patients, and in 10% the serum amylase activity was >
      1000 U/l. Serial measurements of serum salivary (S-) and pancreatic (P-)
      isoamylases indicated that hyperamylasaemia was highest 24 hours after CABG and
      consisted mainly of P-amylase component. Serum creatinine, creatinine clearance
      and urinary albumin concentration remained normal after CABG, excluding severe
      renal damage. The fractional clearance (i.e. relative to creatinine clearance) of
      P-amylase decreased more than of S-amylase (from 3.6 to 0.9% vs 1.3 to 0.8%).
      Decreased rate of excretion into urine, rather than pancreatic cellular damage,
      is the main source of hyperamylasaemia after CABG.

PMID- 9264163
TI  - Long-term follow-up of patients treated with implantable cardioverter
      defibrillators in a Danish centre. Accurrence ICD therpay and patient survivors.
AB  - The aim of the this prospective follow-up study was to evaluate long-term
      survival and implantable cardioverter-defibrillator (ICD) therapy for ventricular
      tachyarrhythmias in patients treated with an ICD in a Danish centre. A total of
      140 consecutive patients (112 men), of which 70.7% had coronary artery disease,
      received an ICD at Skejby University Hospital between March 1989 and October
      1996. Mean age was 55.6 +/- 14.6 years (range 14-78 years). After implantation,
      136 of the patients were followed for a median (range) of 17.7 (0.4-74.1) months.
      Survival, mode of death and incidence of appropriate ICD therapy and therapy due
      to potential life-threatening ventricular tachyarrhythmia were the main outcome
      measures. Kaplan-Meier plots representing total survival, cardiac death, sudden
      cardiac death and first episode of ICD therapy are presented. After 1, 2, 3 and 4
      years, respectively, the cumulative incidences of death were 9, 18, 20 and 24%,
      of cardiac death 4, 11, 14 and 18%, and of sudden cardiac death 2, 3, 6 and 6%.
      The cumulative incidences of appropriate therapy after 1, 2, 3 and 4 years were
      47, 56, 66 and 80%, respectively. The cumulative incidences of cardiac death
      after the first episode of appropriate therapy were 9, 11, 15 and 20% after 1, 2,
      3 and 4 years, respectively. The occurrence of ICD therapy and patient survival
      in the present study population treated with ICD at a Danish centre was
      comparable to results published previously from other larger centres. The rate of
      sudden cardiac death was low and most of our patients received appropriate ICD
      therapy during follow-up, indicating correct patient selection and probable
      benefit of the ICD device.

PMID- 9264161
TI  - Surgical and long-term outcome of graft replacement of aneurysms of the
      descending thoracic aorta. Analysis of 28 consecutive cases.
AB  - A consecutive series of 28 patients operated on at the Oulu University Hospital
      during the years 1974-1994 for aneurysms of the descending thoracic aorta is
      presented. Twenty-five cases were elective and three were operated on as
      emergencies. Their mean age was 58 years. During the aortic cross-clamp,
      circulatory support of the lower body, was used in 27 cases as follows: a direct
      aorto-femoral shunt without a pump (12/28), left-heart bypass (11/28) or femoro
      femoral perfusion (4/28). Hospital mortality was 14% (4/28). One patient with a
      ruptured aneurysm died of renal failure, but there were no other renal
      complications. None had paraplegia postoperatively. Three had symptoms of
      paraparesis, but only one of them had a slight permanent discomfort while
      walking. The mean follow-up time was 100 months, range 2-242 months. Late
      actuarial survival including hospital mortality, was 65% at 5 years and 41% at 10
      years, reflecting the generalized aortic disease with a high risk of very late
      rupture (4) and other manifestations of atherosclerosis with myocardial
      infarction (6) or cerebral atherosclerosis (1), the remaining late deaths being
      unrelated. The efficacy of lower body circulatory support in avoiding
      peroperative renal and spinal cord ischaemic complications is demonstrated.

PMID- 9264162
TI  - Outcome of cardiopulmonary resuscitation following open heart surgery.
AB  - The outcome of cardiopulmonary resuscitation (CPR) following cardiac surgery is
      not known to date. A retrospective analysis of all patients subjected to CPR
      during their hospital stay following heart surgery was conducted; 1.4% of
      patients required CPR 0.5-192 h following surgery. The mean duration of CPR was
      42 +/- 29 min. Twenty-nine patients were subjected to emergency rethoractomy and
      14 patients received coronary artery bypass grafting. The hospital mortality was
      46%. There was a significant correlation of duration of CPR and death (r = 0.44,
      p = 0.004). The commonest cause of death was consecutive multiorgan failure in 12
      patients. Twenty-one patients were long-term survivors without neurological
      sequelae. Twenty patients were in NYHA class I or II. Ventricular fibrillation
      and myocardial ischaemia are the commonest conditions leading to CPR in an
      average population of patients immediately after cardiac surgery. Aggressive
      treatment and emergency rethoracotomy in most cases results in long-term survival
      in 50%.

PMID- 9264164
TI  - Bronchiectasis resulting from aspirated grass inflorescences.
AB  - Bronchiectasis due to aspiration of grass inflorescences is described in three
      children. One patient spontaneously expelled a grass head by coughing and was not
      operated on. The grass inflorescence was found in the right lobe's medial segment
      bronchi in the second case and in the pleural cavity of the third. Pulmonary
      resection was performed in both cases. The clinical manifestations were of both
      "lodging" and "extrusive" types of aspirated grass inflorescence. This
      possibility must be considered in the differential diagnosis of chronic pulmonary
      infections in children.

PMID- 9264165
TI  - Acute dissection of ascending aortic aneurysm in a patient with previous coronary
      artery bypass grafting.
AB  - Six years after coronary artery bypass grafting, a 61-year-old man underwent
      emergency surgery for annulo-aortic ectasia and acute dissection. The aneurysmal
      tissue and aortic valve were excised and reconstruction was achieved with a
      composite graft. The patent vein grafts were attached to the composite graft and
      the original coronary orifices were closed.

PMID- 9264166
TI  - Post-traumatic costochondritis caused by Candida albicans. Aetiology, diagnosis
      and treatment.
AB  - Candida costochondritis is a rare disease of complex aetiology. Pathogenetic
      factors range from postoperative and posttraumatic complications to haematogenous
      dissemination in intravenous drug addicts. In addition to clinical examination,
      possible diagnostic procedures include scintiscan and magnetic resonance imaging.
      The treatment of choice is extensive debridement and resection of the structures
      affected by the inflammatory process. The long-term prognosis is good.

PMID- 9264167
TI  - Surgery of complex coronary arteriovenous fistula.
AB  - A rare type of coronary arteriovenous fistula with multiple supplying vessels
      from both coronary arteries and draining into the pulmonary artery was found in a
      52-year-old woman with angina pectoris. The fistula was successfully closed by
      division of the vessels draining into the pulmonary artery.

PMID- 9264168
TI  - Ivemark syndrome. A case with successful surgical intervention.
AB  - A 19-day-old boy with Ivemark syndrome (splenic agenesis associated with complex
      cardiac malformations and visceral abnormality) underwent palliative surgery
      including Glenn and hemi-Fontan procedures. Five months later the child is alive
      and well. We believe that early palliative surgery is worthwhile in Ivemark
      syndrome with a single ventricle.

PMID- 9264169
TI  - Pneumatocele complicated by fungal lung abscess in Job's syndrome. Successful
      lobectomy with the aid of videothoracoscopy.
AB  - Hyperimmunoglobulin E (Job's) syndrome, is a complex immune disorder
      characterized by complications involving, pulmonary and cutaneous infections. An
      11-year-old girl presented with a pneumatocele superinfected by aspergillosis and
      occupying almost the entire right lower lobe. Lobectomy was performed with the
      aid of videothoracoscopic instruments, and 9 months later the patient is doing
      well.

PMID- 9264170
TI  - Spontaneous double vessel coronary artery dissection. A case report and surgical
      management.
AB  - Spontaneous coronary artery dissection is an uncommon clinical entity, its
      presentation and management similar to atherosclerotic coronary artery disease.
      We report on a young adult male who presented with myocardial infarction due to
      simultaneous dissection of left anterior descending and right coronary artery. He
      was treated with bilateral interal mammary artery grafts.

PMID- 9264171
TI  - Neuroendocrine blockade in coronary surgery. A clinical study with reference to
      myocardial metabolism and performance.

PMID- 9264172
TI  - Urban birth and residence as risk factors for psychoses: an analysis of 1880
      data.
AB  - It is known that social drift to cities increases the urban prevalence for severe
      mental illnesses. Recent studies in England and Sweden have reported that being
      born in, or raised in, an urban area is also a risk factor for later developing
      schizophrenia. The present study utilized 1880 census data, the most complete
      enumeration of severely mentally ill individuals ever done in the United States,
      to examine the association of urban residence and severe mental illnesses.
      Individuals identified as having one of seven forms of 'insanity' (n = 91959)
      were allocated to their county of origin (n = 2661) in the census. Rates of
      'insane' persons per 1000 population were calculated for each county. The
      counties were then divided by degree of urbanization based on the largest cities
      and the percentage of population living in towns of 4000 or more. The point
      prevalence of 'insanity' in the United States as a whole in 1880 was 1.8 per
      1000. There was a significant association between 'insanity' by county and degree
      of urbanization, with odds ratios of 1.66 for urban, 1.46 for semi-urban, and
      1.44 for semi-rural, and 1.37 for rural, using completely rural counties as a
      baseline. Most completely rural counties with high rates included mining camps,
      lumbering camps, or fishing villages, and not farming areas. In addition to urban
      drift, urban birth and residence appear to be risk factors for developing severe
      mental illnesses. Psychological and biological explanations have both been
      proposed. However, recent studies reporting winter birth and urban birth or
      residence as synergistic risk factors favor the latter.

PMID- 9264173
TI  - Schizophrenia, rheumatoid arthritis and natural resistance genes.
AB  - The strong negative correlation between schizophrenia and rheumatoid arthritis
      might provide clues as to the aetiology of these two diseases. An immunological
      explanation has been sought in the HLA sector of the major histocompatibility
      complex, which has been shown to have a role in the development of rheumatoid
      arthritis. The search for an association between schizophrenia and HLA
      haplotypes, however, has yielded only controversial results. Nevertheless, an
      autoimmune aetiology is still suspected. The recent demonstration of geographical
      co-occurrence of high rates of schizophrenia and flavivirus infection suggests,
      for the first time, that a natural resistance gene (NRG) might be involved in the
      aetiology of schizophrenia. Such a NRG is carried by the C3H/RV mouse, providing
      protection against lethal infection by flavivirus, but not by the histocompatible
      C3H/He mouse. Furthermore, the C3H/He mouse has proved to be a good model for the
      development of Lyme arthritis, resulting from infection by Borrelia burgdorferi.
      It is suggested that there is a possibility that the C3H/RV mouse, which is known
      to be resistant to both flavivirus and rickettsia, may also be resistant to
      borrelia, since the Ixodid tick vector of flavivirus is the vector for all three
      of these organisms. If so, then the C3H/RV mouse would resist infection by
      borrelia, and could not develop Lyme arthritis. It is hypothesised, therefore,
      that despite the histocompatibility of these two strains, while the C3H/He mouse
      is vulnerable to Lyme arthritis, the C3H/RV mouse may be resistant. As a
      consequence, NRGs may play a part in triggering autoimmune disease, with HLA
      antigens responsible for its further development. This would indicate that the
      negative association of schizophrenia and rheumatoid arthritis could result from
      resistance or vulnerability to certain infections.

PMID- 9264174
TI  - A new approach to discourse analysis in psychiatry, applied to a schizophrenic
      patient's speech.
AB  - OBJECTIVE: Progress in the science of data analysis and computer technology has
      led to the development of advanced methods for investigating structure discourse
      in the psychiatric field, where language constitutes a useful investigative and
      therapeutic tool. The purpose of this study was to present and use a computer
      assisted method of discourse analysis (Alceste-software) to analyse the
      schizophrenic subject's oral contributions regularly collected for 3 months.
      METHOD: The method used consisted of modelling the main word distribution in
      spoken recordings pooled together and identifying the repetitive language
      patterns most frequently used by the speaker. RESULTS: Four main kinds of
      discourse emerged from the pool of schizophrenic's speech samples, on specific
      topics without any lack of ability to organize the material, but the technique
      analysis showed that the main kinds of discourse were interspersed with
      unexpected 'language satellites' consisting of a secondary short and specific
      discourse which was also well planned but had no relevance to the main discourse
      making for a lack of cohesion in the speech samples. This method allows us direct
      access to the inner experience of the patient. The technique highlighted a very
      poor pre-syntax linked to the choice of words and a tendency to make pronoun
      errors, possibly reflecting some confusion between the patient herself and
      others, mainly her mother, especially in the discourse about childhood.
      CONCLUSION: This method of discourse analysis made it possible to investigate
      various language disturbances at the same time and at different levels. It is
      particularly adapted for analysing the schizophrenic's speech. The data obtained
      were consistent with the assumption that schizophrenia involves 'thought
      disorders': these ones giving rise to the language impairments.

PMID- 9264175
TI  - Attribution of intentions to others in people with schizophrenia: a non-verbal
      exploration with comic strips.
AB  - Several clinical and experimental data suggest that some people with
      schizophrenia have an impaired ability to attribute relevant mental states to
      other people. We tested this notion in 24 schizophrenic patients and two control
      groups, who performed a task devised to test understanding of the intentions of
      nonverbal comic strip characters. Only the schizophrenic subjects with thought
      and speech disorganization had specific difficulties attributing mental states to
      others. The findings support cognitive models which postulate a link between
      planning process disorders and a deficit in mentalizing skills. The hypothesis
      that the more frequent an action is in everyday life, the more easily it is
      understood by schizophrenic subjects, is discussed.

PMID- 9264176
TI  - Clinical symptom dimensions and deficits on the Continuous Performance Test in
      schizophrenia.
AB  - We examined the relationships between symptom dimensions derived from factor
      analytic studies of schizophrenic symptoms and sustained attention deficits. Four
      factors, negative, delusion/hallucination, disorganization, and excitement, were
      yielded from factor analysis on 14 items of the Positive and Negative Syndrome
      Scale (PANSS) among 60 Chinese inpatients with acute schizophrenia. The negative
      dimension was associated with lower sensitivity index (d') while the excitement
      dimension was associated with higher d' on the Continuous Performance Test (CPT)
      after sex, age and education were adjusted for in multiple linear regressions.
      The positive dimension affected only response criterion (ln beta) and was not
      associated with the d' on the CPT. In contrast, the summed scores of PANSS
      Positive and Negative scales did not have significant correlations with d' on the
      CPT. Thus, the discriminant validity of these symptom dimensions of schizophrenia
      is supported by their correlations with CPT performance indices.

PMID- 9264177
TI  - Differential pathophysiological mechanisms of reduced P300 amplitude in
      schizophrenia and depression: a single trial analysis.
AB  - In order to address basic mechanisms behind a reduced averaged P300 wave in
      schizophrenia and depression, 17 unmedicated schizophrenic and 11 unmedicated
      depressive subjects were tested in an 'oddball paradigm' against healthy controls
      matched for gender and age. The amplitude distributions of single trials' maximum
      positive deflections after stimulation (P300) for both target and nontarget
      stimuli were determined, which served as a basis for calculating the
      discrimination index d'. This index characterizes differences in the
      electrophysiological responses to target and nontarget stimuli of a subject being
      engaged in a discrimination task. As a main result d' was significantly lower for
      schizophrenics than for their controls. Directly compared to depressive subjects,
      schizophrenics also depicted a statistically significant decrease of the
      discrimination index, which could not be explained by differences in age.
      Although the averaged P300 signals did not show any significant differences
      between the two diagnostic groups, the approach of calculating d' on the basis of
      single trial analysis differentiated between schizophrenics and depressives. In
      conclusion, schizophrenic patients revealed different functional features when
      generating event-related potentials in an 'oddball paradigm' compared to healthy
      controls and depressives.

PMID- 9264178
TI  - Behavioral and P3 amplitude enhancement in schizophrenia following feedback
      training.
AB  - In order to clarify the remediability of behavioral and electrophysiological
      abnormalities in schizophrenia, hit rate, reaction time, and P3 amplitude from
      auditory event-related potentials were evaluated before and after feedback
      training of a task in 14 schizophrenics and 12 age-matched normal controls.
      Although mean changes in the three indices due to the training were
      nonsignificant in both schizophrenic and normal control groups as a whole, the
      changes in hit rate and reaction time correlated significantly with the P3
      amplitude change in the schizophrenic (r = 0.60 and -0.58, respectively) but not
      in the normal control group. The P3 amplitude change also correlated with the P3
      amplitude before the training only in the schizophrenic group (r = -0.68),
      suggesting that the training was more effective for the schizophrenic patients
      with marked P3 amplitude reduction. The observed P3 amplitude increase due to
      training may represent an electrophysiological correlate of a remediable aspect
      of behavioral deficits in schizophrenics, which may underlie the effectiveness of
      nonpharmacological treatments.

PMID- 9264179
TI  - Bladder dysfunction in schizophrenia.
AB  - In schizophrenic patients with incontinence our previous urodynamic studies
      showed detrusor hyperreflexia in some cases. Many schizophrenic patients have
      brain abnormalities similar to those associated with urge incontinence and
      detrusor hyperreflexia in neurological patients. We therefore propose bladder
      dysfunction and incontinence as previously unrecognized neurobiological
      correlates of schizophrenia. To clarify this concept our first step, the present
      study, was a patient survey for urinary problems. Incontinence was more prevalent
      in schizophrenic patients than in a comparison group of mood disorder patients at
      the same hospitals. Urge incontinence and leakage of any type were related
      closely to psychiatric diagnosis. These data, like our pilot urodynamic studies,
      suggest that incontinence represents detrusor hyperreflexia in a significant
      subset of schizophrenic patients. Prospective urodynamic studies will be needed
      to test our proposal directly.

PMID- 9264180
TI  - Glutamate dehydrogenase mRNA is immediately induced after phencyclidine treatment
      in the rat brain.
AB  - To clarify the molecular mechanism of phencyclidine (PCP)-induced
      schizophreniform psychosis in humans and of behavioral abnormalities in
      experimental animals, we used differential screening of a cDNA library from the
      cerebral cortex of rats treated with PCP. We identified a PCP-induced cDNA clone
      as the gene encoding glutamate dehydrogenase (GDH), an enzyme central to
      glutamate metabolism. GDH mRNA levels significantly increased as early as 15 min
      following PCP administration in both the cerebral cortex and the cerebellum. This
      effect was observed even in the presence of a protein synthesis inhibitor,
      cycloheximide. In contrast to a transient increase in c-fos expression, the
      elevation of GDH mRNA levels lasted up to 8 days after a single PCP injection.
      These results suggest that GDH mRNA induction may be involved in the pathology of
      PCP-induced psychosis, and that GDH may be one of the candidate genes that are
      vulnerable in subjects with schizophrenia.

PMID- 9264181
TI  - Clozapine-reserpine combination for refractory psychosis.

PMID- 9264182
TI  - Dissociation of W/REM/NREM states may cause psychotic symptoms.

PMID- 9264184
TI  - [Habitual dependence on modern imaging modalities: the new golem].
AB  - Modern imaging techniques have been taking over our medical life, but none denies
      the progress that has followed introduction of modern imaging modalities. For the
      generation of younger physicians who entered the profession after the
      introduction of these techniques, use of US, CT, MRI and the like is natural and
      often applied. But the patient is not computerized and medicine is far from being
      a pure science. 3 cases of common surgical problems are presented in which
      excessive use of diagnostic modalities resulted in unnecessary operations, thus
      leading to unnecessary morbidity. In these days of soaring medical expenses, many
      unnecessary imaging and laboratory studies are done for reasons of "defensive"
      medicine. It is important to fortify the position of clinical diagnosis, but
      making clinical decisions without requiring expensive and sometimes misleading
      imaging studies significantly reduces costs. Admittedly, courage and firm
      professional backbone are required to face a lawyer or a judge and say: "This CT
      or US study would not have changed my clinical decision; it would have made no
      positive contribution to it, and might even have mislead me." This paper comes to
      remind physicians of the importance of clinical diagnosis and the need to develop
      and rely on primary medical skills. Machines and laboratory tests are aids to
      diagnosis, they do not make the diagnosis.

PMID- 9264183
TI  - [International quality assurance standards (ISO 9002) in an Israeli hospital].
AB  - This hospital has been certified by the Israel Standards Institute as having a
      quality assurance system fulfilling the requirements of the international
      standard, ISO 9002. This is the first hospital in this part of the world to be
      certified as fulfilling this standard. Its adoption is one of several accepted
      approaches to quality assurance in medicine. World-wide, very few health
      organizations, including hospitals, have implemented this system successfully.
      Opinions regarding its importance are divided, mostly because of lack of
      experience in its application. We describe its features, goals and structure, and
      its implementation in various sectors, including health organizations. The
      process of its adoption, application and implementation is described, and the
      problems which arose are discussed.

PMID- 9264185
TI  - [Distraction osteogenesis for hypoplastic facial bones].
AB  - Distraction osteogenesis is a well-known method for bone lengthening which
      stretches callus to generate new bone in the distracted area. The method was
      developed by Ilizarov for the lengthening of long enchondral bones. In recent
      years the method has also been applied to the facial bones and to the jaw.

PMID- 9264186
TI  - [Hyponatremia due to prolonged excessive ingestion of water].
AB  - We report a 1.5-year-old boy admitted for restlessness and constipation. He was
      found to have hyponatremia caused by voluntary drinking of excessive amounts of
      water. Although unusual in children, intoxication by oral water is a recognized
      clinical syndrome in infants, 3-6 months old, fed with dilute formula. Water
      intoxication in older children is rare. The diagnosis was established by the
      water deprivation test.

PMID- 9264188
TI  - [Traumatic common carotid-internal jugular fistula: positive aspect].
AB  - A 42-year-old man presented with a penetrating neck injury from a pellet gun.
      Physical examination showed an open 1 cm wound on the right side of the neck,
      hematoma of the right sternocleidomastoid muscle, and carotid artery injury. He
      was hemodynamically stable and there was no neurological deficit. Arteriogram of
      the neck disclosed a pseudoaneurysm with an arteriovenous fistula between the
      common carotid artery and internal jugular vein. At surgery, the tears in the
      carotid artery and jugular vein were sutured and a vacuum drain was introduced.
      The postoperative course was uneventful, and the patient was discharged 5 days
      later. Instead of the expected results of a penetrating carotid artery injury,
      such as blood loss, airway obstruction or neurological deficit, the arteriovenous
      fistula caused by the pellet actually saved the patient's life. Blood flow from
      the artery via the pseudoaneurysm to the jugular vein kept the patient in stable
      condition.

PMID- 9264187
TI  - [Effect of chlorocresol vs caffeine on muscle contracture in malignant
      hyperthermia susceptible patients].
AB  - The phenotype of susceptibility to malignant hyperthermia (MHS); can only be
      detected reliably by the in vitro caffeine-halothane contracture test (CHCT).
      Enhanced sensitivity of the calcium-induced calcium release mechanism is
      responsible for the exaggerated contracture response of skeletal muscle fibers
      from MHS patients to halothane and caffeine. Chlorocresol was demonstrated to be
      a potent activator of Ca++ release from skeletal muscle sarcoplasmic reticulum.
      This effect is probably mediated through action on a ryanodine sensitive Ca++
      release channel known to be more sensitive in MH. We studied the effect of
      chlorocresol on the mechanical contracture response of skeletal muscle from
      patients presenting for the in vitro CHCT. Chlorocresol induces contracture
      response in a concentration 1/200 of that of caffeine in muscle strips from MH
      patients. By adding chlorocresol to the protocol of the CHCT, there is clearer
      discrimination between the responses of MH patients and normal subjects can be
      achieved.

PMID- 9264190
TI  - [Road traffic accidents--a public health issue].

PMID- 9264189
TI  - [Embolic splenic infarction: a rare complication of atrial fibrillation].
AB  - Splenic infarction is a rare disorder. The typical clinical presentation is
      sudden pain in the left upper quadrant of the abdomen, and awareness to this
      possibility is the major clue for diagnosis. We describe a 49-year-old man with
      chronic atrial fibrillation and splenomegaly who was treated with anticoagulants.
      Because of hematuria, the regular dose of anticoagulant therapy was reduced. The
      hematuria stopped but he complained of sudden onset of pain in the left upper
      quadrant. Computerized tomography and isotope scan of the spleen confirmed the
      clinical suspicion of splenic infarction. Treatment with anticoagulants and
      analgesics was followed by clinical improvement.

PMID- 9264191
TI  - [Receptors, genetics and malignant hyperpyrexia].

PMID- 9264192
TI  - [The Internet and geriatric medicine].

PMID- 9264194
TI  - [Familial ovarian cancer].

PMID- 9264193
TI  - [Molecular biology of melanoma--1997].

PMID- 9264195
TI  - [Genetic risk factors for diabetic complications].

PMID- 9264197
TI  - [Bacterial vaginosis and preterm labor].

PMID- 9264196
TI  - [Blood and urinary level of methylmalonic acid: an important index in evaluating
      cobalamin deficiency].

PMID- 9264198
TI  - [Calcium blockers and cancer--is there any link between them?].

PMID- 9264199
TI  - [The use of intuition--conceptual aspects and clinical significance].

PMID- 9264200
TI  - [Dobutamine stress-echocardiography].

PMID- 9264201
TI  - [Post-antibiotic effect and the principle of once-a-day aminoglycoside
      administration].

PMID- 9264202
TI  - [Halachic aspects of the right of the terminally ill to know].

PMID- 9264203
TI  - [Airway management of the multiple trauma patient].

PMID- 9264204
TI  - [Femoral neuropathy in a patient with unstable angina].

PMID- 9264205
TI  - Public health in medical education.

PMID- 9264206
TI  - Diphyllobothriasis after eating raw salmon.
AB  - An 11-year-old boy in Hawaii passed mucus and a moving object in his stool. The
      object was identified as a segment of the fish tapeworm Diphyllobothrium species
      which is not indigenous to Hawaii. Diphyllobothrium ova were also found in the
      stool. The only raw fish he recalled eating in previous months were tuna sushi
      and lomi-lomi salmon which usually contains raw but previously frozen salmon. Of
      these two fish, only salmon which is not native to Hawaiian waters, has been
      incriminated as a significant source of diphyllobothrium fish tapeworm infection.
      Freezing kills this parasite, however, we speculate that the raw fish in the lomi
      lomi salmon that our patient had eaten had not been pre-frozen or was not
      adequately pre-frozen. Eating raw salmon without certainty that it has been
      adequately pre-frozen carries the risk of diphyllobothriasis or fish tapeworm
      infection.

PMID- 9264207
TI  - Project caring for life--long-term care funding alternative.
AB  - The synopsis of The Hawaii Long-Term Care Task Force describes the product of
      project: "Caring ... For Life" as "the framework for implementation of a long
      term care system. Framework will encompass promotion, programs, education,
      legislation and other initiatives necessary for an effective system. The product
      will be a combined effort of the private sector and government to bring about
      changes which will provide a continuum of services to all residents in need of
      long-term care in the least intensive, most appropriate and affordable setting."
      The purpose of this concept paper has been to paint the big picture of LTC as it
      now is and provide, in concept, an alternative picture of what it could be. It is
      by no means complete but hopefully will serve as an initial effort to be
      addressed and, if appropriate, be expanded upon or modified. It could also serve
      as a basis of comparison for other alternatives as they are considered. Long-term
      care is a complex problem, there are no quick fixes. The solution will require
      great imagination and the ultimate of our creativity. The product should be
      flexible and above all, should be able to stand the test of time.

PMID- 9264208
TI  - It's complete disclosure time.

PMID- 9264209
TI  - Insurance claims: protect yourself from becoming the next one in 10.

PMID- 9264210
TI  - A clinical decision making framework for the medically compromised patient:
      ischemic heart disease and chronic obstructive pulmonary disease.
AB  - The intent of this article is to assist dentists and their staff in the
      assessment of systemic disease, and establish a framework for clinical decision
      making that correlates medical risk with the anticipated complexity of the
      planned dental procedures. Two examples of systemic disease, ischemic heart
      disease (IHD) and chronic obstructive pulmonary disease (COPD), are discussed in
      terms of pathophysiology, risk factors, clinical manifestations of disease and
      disease progression.

PMID- 9264211
TI  - Oral squamous cell carcinoma: new insights.
AB  - Squamous cell carcinoma is the most common form of oral cancer, and causes more
      deaths than any other oral disease. Dentists and dental auxiliaries must know the
      clinical, etiologic, pathogenetic and prognostic features of squamous cell
      carcinoma to ensure appropriate screening and diagnosis of the patient. It is now
      recognized that cancers are genetic diseases, which arise from inherited genetic
      factors and exposure to exogenous carcinogens that alter the DNA of cells.
      Increasingly, the genetic events that contribute to the development of cancers at
      many sites within the body are being identified, and the complex series of
      genetic steps required for fully-developed neoplasia to arise in the oral cavity
      are being better characterized. This article reviews recent advances in the
      understanding of the etiology and pathogenesis of oral carcinoma, including the
      involvement of various oncogenes, tumor suppressor genes and viruses.

PMID- 9264212
TI  - New developments in selected cysts of the jaws.
AB  - The number and variety of cysts that occur in the jaws are greater than those in
      any other part of the body. Consequently, dental practitioners must keep up with
      advances in this field, including the definition of new entities, such as the
      glandular odontogenic cyst; the deletion of the old incorrect concept of
      maxillofacial fissural cysts, including the globulo-maxillary cyst; and the
      advances in the molecular biology of established cysts, such as the dentigerous
      cyst and the odontogenic keratocyst.

PMID- 9264213
TI  - Gingival cyst of the adult: a review and a report of eight cases.
AB  - The gingival cyst of the adult (GCA) is an uncommon gingival lesion that is
      usually found within attached or unattached soft tissues. It is generally
      considered to be a cyst of odontogenic origin, though this is still debated
      somewhat. This article reviews the diagnosis and treatment of GCA and summarizes
      the features of eight cases.

PMID- 9264214
TI  - Dental practice transitions: potential problems and possible solutions.

PMID- 9264215
TI  - A survey of general dentists in Ontario, Part I: Sealant use and knowledge.
AB  - This study assessed the use of pit and fissure sealants by Ontario dentists, as
      well as variations in the knowledge and practices of this population with respect
      to certain aspects of the preventive technique. A mail questionnaire on dental
      practices and knowledge was answered by 1,276 general dentists in Ontario. Most
      dentists (90 per cent) provided sealants to their patients, and reported using
      sealants on an average of 45 per cent of their patients between the ages of six
      and 16 years. While most dentists knew that sealants have been proven effective
      in preventing caries (90 per cent), many incorrectly believed that sealants are
      cost-effective to apply to both primary molars and permanent premolars (40 per
      cent and 68 per cent respectively). Bivariate analyses showed that many of the
      reported characteristics are statistically significant. The variables that were
      consistently associated with sealant use include: knowledge of the effectiveness
      and cost-effectiveness of sealants; year of graduation from dental school; level
      of dental hygienist employment; and continuing education participation. Although
      multivariate analyses identified many of these variables as statistically
      significant, only a moderate amount of the variation in sealant use for patients
      aged six to 16 was explained (R2 = 0.22). Due to misinformation about the cost
      effectiveness of sealants, some dentists may overuse them in certain instances.
      Conversely, misinformation about the effectiveness of sealants and the risk of
      further decay after sealant placement has resulted in some dentists under
      utilizing them. Continuing education courses are needed to update dentists'
      knowledge and beliefs regarding dental sealants. In addition, dentistry's
      professional bodies should develop clinical practice guidelines to aid dentists
      in their treatment planning decisions.

PMID- 9264216
TI  - Fissure sealants and dental dam.

PMID- 9264217
TI  - Hypertension and obesity in African-American patients undergoing surgery.
AB  - This study was designed to determine the prevalence of hypertension and obesity
      in a population of African-American patients scheduled to undergo surgery. Weight
      and blood pressure were measured in 431 randomly selected patients. This included
      282 women (65%) and 149 men (35%). Hypertension was present in 27% of the women
      and 32% of the men. Obesity was present in 58% of the women and 23% of the men.
      Fifteen percent of all patients met the criteria for having both hypertension and
      obesity. This study confirms the high incidence of hypertension and obesity in
      the African-American population. The high morbidity and mortality associated with
      these conditions suggest that a renewed community-wide effort and public
      education program on the part of health-care providers is needed to inform this
      patient population of these dangers.

PMID- 9264218
TI  - Promotion of mental health through coaching competitive sports.
AB  - Competitive sports can have a negative or positive impact on an athlete's mental
      health, and an athlete's coach plays a large role in determining this. The
      coach's goal should be to help athletes realize that developing human potential
      is equally as important as winning. This article highlights guidelines to assist
      coaches in instructing and mentoring athletes.

PMID- 9264219
TI  - Hyperinsulinemia and acanthosis nigricans in African Americans.
AB  - Compared with the US white, non-Hispanic population, the African-American
      population has a nearly two-fold higher prevalence of noninsulin-dependent
      diabetes mellitus (NIDDM). Obesity, which usually precedes NIDDM, is associated
      with the skin lesion acanthosis nigricans in African Americans. This study was
      undertaken to determine what the relationship of acanthosis nigricans was to
      hyperinsulinemia, a major risk factor for NIDDM. Eighty-nine African-American
      subjects with acanthosis nigricans and 25 others without the skin lesion were
      evaluated using oral glucose tolerance testing and responsiveness to insulin.
      Noninsulin-dependent diabetes mellitus was present in 19 of the subjects with
      acanthosis nigricans. The prevalence of NIDDM in this group increased with
      increasing age, reaching 50% among those in their 40s. Fasting plasma insulin
      concentration was in direct proportion to the severity of the acanthosis
      nigricans involvement of the neck. These data suggest that among African
      Americans, this skin lesion is a marker for hyperinsulinemia and insulin
      resistance. Furthermore, the presence of acanthosis nigricans identifies a subset
      with a much higher prevalence of NIDDM than is present in African Americans in
      the general population.

PMID- 9264220
TI  - Total hip reconstruction in a woman with Cornelia de Lange syndrome: a case
      report.
AB  - More than 250 cases of Cornelia de Lange syndrome have been reported in the
      medical literature, but not have described the use of hip reconstruction to
      correct the congenital dysplasia that may be associated with this condition. This
      article reports the application of a bipolar hemiarthroplasty and acetabular
      allograft reconstruction for a 32-year old woman with congenital dysplasia and
      degenerative joint disease of the hip secondary to de Lange's syndrome. On
      admission, she was in considerable pain and unable to bear weight on the affected
      extremity. Her Harris hip score was 25. Following surgical intervention and a
      well-designed plan of rehabilitation, the patient's functional status improved
      markedly. Her Harris hip score was 72, and her pain was alleviated.

PMID- 9264223
TI  - The occurrence of endometrial adenocarcinoma in a patient with basal cell nevus
      syndrome.
AB  - Basal cell nevus syndrome is rare multisystem disorder. Its genital implications
      in female patients is thought to be limited to ovarian fibroma. This article
      describes endometrial adenocarcinoma in association with basal cell nevus
      syndrome in a 37-year-old female with multiple basal cell carcinomas, mandibular
      and maxillary bone cysts, right ovarian fibroma, and scoliosis. Histopathologic
      examination of her endometrial biopsy, performed for irregular uterine bleeding,
      revealed endometrial hyperplasia. Her bleeding failed to respond to progestin
      therapy, and a repeat endometrial biopsy revealed a well differentiated
      endometrial adenocarcinoma. Health-care providers are encouraged to refer these
      patients to gynecologists. Regular gynecologic examination as well as appropriate
      evaluation of abnormal menstrual bleeding should be emphasized.

PMID- 9264222
TI  - Intravenous immunoglobulin in symptomatic and asymptomatic children with
      perinatal HIV infection.
AB  - One hundred thirty-five children born to human immunodeficiency virus (HIV)
      infected mothers were selected randomly to receive immunoglobulin (Gamimune-N,
      Miles Pharmaceutical Co) 200 mg/kg monthly for 1 year. All patients were
      seropositive by ELISA and Western blot at birth. At the time of the study, 15
      symptomatic (P2) and 57 asymptomatic (P1) patients with evidence of viral
      infection (positive HIV culture or P24 antigen) received the immunoglobulin.
      Sixty-three indeterminate (PO) patients with no evidence of infection served as
      the control. Mean age for infants in group P2 was 32 months, 26 months for group
      P1, and 11 months for group PO. Significant reduction in the frequency of
      bacterial infections (ie, otitis media, upper respiratory tract infections,
      urinary tract infections, and acute gastroenteritis) was seen in the symptomatic
      group compared with both the asymptomatic and the control groups. Growth as
      measured by weight and height > 50th percentile was also markedly better in the
      symptomatic group than either asymptomatic or control patients. There was no
      significant difference in head circumference in all three groups. These results
      indicate that monthly intravenous immunoglobulin infusion (IVIG) appears to be
      beneficial to both symptomatic and asymptomatic HIV patients in reducing the
      frequency of bacterial infection and also enhancement of the immune response.
      However, symptomatic patients responded much better than the asymptomatic
      patients.

PMID- 9264221
TI  - African-American physicians and smoking cessation counseling.
AB  - While African American physicians can play a key role in encouraging black
      patients who smoke to quit, little is known about the views and activities of
      these physicians with respect to antitobacco programming. In the process of
      developing a protocol for encouraging physicians' smoking cessation intervention,
      96 African-American physicians completed a survey indicating their knowledge,
      attitudes, and practices relating to stop smoking counseling. Few physicians
      reported patient help-seeking behavior and 47.9% cited lack of patient motivation
      as a key barrier to intervention. Only 46.8% believed that it is possible to
      accomplish a lot of cessation help in a few minutes time, and 34.4% believed that
      setting up and maintaining an office protocol would require a great deal of
      effort. Explaining health risks (71.9%) and enrolling patients in programs
      (66.6%) were perceived as keys to patient cessation; fewer than half of the
      physicians surveyed discuss specific strategies for quitting with their patients.
      Physicians indicated a willingness to offer more counseling in the future and
      were open to a range of strategies for learning more about effective approaches.
      Our findings support the need for dissemination of such information, particularly
      among specialists, to support antitobacco efforts among African-American
      physicians.

PMID- 9264224
TI  - Homage to the NMA: the NDA story (1895 to 1975)--Part 2.

PMID- 9264225
TI  - Munchausen's syndrome: a medico-legal dilemma.
AB  - In his or her life-long career, the physician will eventually encounter a patient
      with factitious disorder, or Munchausen's syndrome. We discuss two patients
      complaining of renal colic that were identified as having Munchausen's syndrome.
      We review the literature to identify certain aspects of the disease and to
      discuss the medical and legal implications for the treating physician and
      hospital.

PMID- 9264226
TI  - Psychiatric in-patient suicide rates: a 21-year study.
AB  - Psychiatric in-patient suicides were traced from the hospital death register for
      the 21-year period 1973 to 1993. Suicide rates for each of the 21 years were
      calculated and an overall rate of 3.68 per 1,000 admissions was found. Suicide
      rates for the period after 1987 were significantly lower than for the period
      before 1987. However, there was a significant upward trend during the last three
      years of the study period. The role of the new Mental Health Act (introduced in
      1987) on reducing the suicide rate and the effects of the amalgamation of three
      hospitals on increasing the rate are discussed.

PMID- 9264227
TI  - Unexpected death of psychiatric patients: suicide, misadventure, accident or
      unsolved mystery?
AB  - We examined the association between the psychiatric history of patients who were
      the subjects of a coroner's inquest and the recorded verdict, in a seven-year
      retrospective review. A suicide verdict was less frequently returned on patients
      who had inpatient psychiatric treatment compared to other unexpected deaths.
      History and diagnosis of an alcohol-related condition, method of death and
      intimation of intent were the main factors that appeared to be associated with
      the coroner's verdict. Age, sex, duration of illness, time and number of
      admissions, previous suicide attempts and treatment received did not appear to be
      significantly associated with the recorded verdict.

PMID- 9264228
TI  - AIDS: safety, regulation and the law in procedures using blood and blood
      products.
AB  - The purpose of this paper is to examine issues of regulation of the market for,
      and use of, blood and blood products. The situation has changed since the
      discovery of the Human Immune Deficiency Virus (HIV), the presumed cause of AIDS,
      because it was recognized that some haemophiliacs were infected with HIV from
      transfused blood and blood products before 1985. When the danger was realized in
      that year, regulations were introduced internationally to prevent this, but
      meanwhile some haemophiliacs developed AIDS. In several countries, governments
      have accepted responsibility, without liability, for possible transmission of
      infection, and paid compensation to victims. In France three health service
      officials have been convicted of fraud and criminal negligence. In March 1997 a
      trial began in Japan of three drugs company executives accused of promoting the
      sale of HIV-contaminated blood products. Since then there has been a class action
      in the USA resulting in awards. Further issues have arisen with regard to the
      outcome and treatment of asymptomatic infection with HIV. The implications for
      public safety, and for medical and legal practice, are far reaching and reveal a
      need for more effective monitoring of the existing procedure for supply and
      clinical use of blood and blood products.

PMID- 9264229
TI  - 'Fitness to be interviewed'--a proposed definition and scheme of examination.
AB  - Police surgeons are frequently asked by the police to assess whether suspects
      held in police custody are fit to be interviewed. The lack of any clear medical
      and legal criteria by which fitness for interview can be assessed has left many
      doctors confused about what exactly the term means. This paper draws attention to
      the importance of the topic and suggests a working definition of 'fitness to be
      interviewed.' A scheme of examination is proposed which should enable the police
      surgeon to make a meaningful assessment of a suspect's fitness for interview.

PMID- 9264230
TI  - Reye's syndrome.
AB  - Reye's syndrome is a rare disorder appearing almost always in childhood. It is
      characterized by acute encephalopathy and fatty degeneration of the viscera. The
      mortality is high and many survivors have neurologic sequelae. A viral illness,
      particularly varicella or influenza B, usually precedes the syndrome. It has been
      associated with the use of aspirin during such infections. The number of cases
      has declined in countries where there has been a public education campaign and
      aspirin products have been withdrawn from sale. It is suggested that the same
      campaign is initiated in Denmark.

PMID- 9264232
TI  - Detection of bromisovalum from the bone marrow of skeletonized human remains: a
      case report with a comparison between gas chromatography/mass spectrometry
      (GC/MS) and high-performance liquid chromatography/mass spectrometry (LC/MS).
AB  - We report a case of totally skeletonized human remains in which a considerable
      amount of a hypnotic, bromisovalum (bromovalerylurea), was detected from the bone
      marrow. The unknown skeletal remains were found in a bush, together with empty
      vials of bromisovalum and a water bottle. The body was identified as a 46-year
      old male, who had died about seven months previously. There was no evidence of
      trauma. The dried bone marrow of both femurs was separately collected and
      toxicologically analysed by gas chromatography/mass spectrometry (GC/MS) and a
      high-performance liquid chromatography/mass spectrometry (LC/MS). Bromisovalum
      was identified from the femurs. The concentration along with the circumstantial
      evidence suggested possible contribution of bromisovalum to the fatality.
      However, a considerable quantitative difference was observed between the left and
      right femur, showing significant post-mortem interference to toxicological
      evidence. The result showed that multiple sampling at least would be required for
      quantitative evaluation of post-mortem toxicological evidence. Moreover, the
      diagnostic value should also be considered with caution in relation to the load
      to bone marrow ratio of each drug concentration.

PMID- 9264231
TI  - Sudden unexpected death in young adults including four cases of SADS: a 10-year
      review from the west of Ireland (1985-1994).
AB  - Sudden unexpected death in young adults of 18-35 years account for an important
      subset of deaths in our autopsy population. The case notes and autopsy reports in
      44 subjects were analysed during the period 1985-94 at the Department of
      Histopathology, University College Hospital, Galway to establish the underlying
      cause of death. Subjects who were involved in road traffic accidents, cases of
      drowning, and patients with known congenital heart disease, chronic renal failure
      and malignancy were excluded. We found that a large proportion of sudden deaths
      in young adults were secondary to epilepsy and chemical/drug poisoning,
      accounting for 34 per cent and 31.8 per cent respectively. Sudden adult death
      syndrome (SADS) accounted for 9 per cent of the study population. Detailed case
      history, meticulous post-mortem examination and complete toxicological screening
      are recommended to arrive at the underlying cause of death.

PMID- 9264233
TI  - Unusual presentation of colloid cyst of the third ventricle.
AB  - This case report describes death in a young male, six months after an assault.
      The death was caused by a colloid cyst, a rare but important malformation in the
      brain. The possible relationship between the assault and the cyst is discussed.

PMID- 9264234
TI  - Unusual post-mortem autolytic change in the liver: wavy transformation of
      hepatocytes.
AB  - An unusual morphologic change noted in the liver of a 21-year-old male who
      committed suicide by taking dimenhydrinate is described. The post-mortem interval
      was two days. Microscopically, there were no marked ante-mortem pathologic
      changes. In addition to the unusual post-mortem autolytic changes, such as
      disappearance of the hepatic cords and shrinkage of the hepatocytes, conspicuous
      way transformation of the hepatocytes, which was apparently never been reported
      before, was observed. This change could not be identified as an artifact, and it
      was assessed to be a type of autolysis.

PMID- 9264235
TI  - Significant coincidental findings at autopsy in accidental childhood death.
AB  - Three cases of unexpected childhood death are presented in which significant
      potentially life-threatening lesions were identified that were considered
      coincidental to the cause of death. Two children died of accidental asphyxia and
      one died of potassium fluoride poisoning. Abnormalities identified at autopsy
      included established myocarditis (two cases) and cardiac rhabdomyomas (one case).
      In one case a previously unsuspected abnormal familial karyotype was found. These
      cases emphasize the value of complete autopsy investigations in all types of
      sudden childhood death, even when the cause of death appears obvious; they also
      demonstrate that potentially lethal organic disease may be asymptomatic in
      childhood and unrelated to death.

PMID- 9264236
TI  - Arrhythmogenic right ventricular dysplasia (ARVD): an overlooked and
      underdiagnosed condition?
AB  - We present three cases of arrhythmogenic right ventricular dysplasia causing or
      contributing to sudden death. These cases serve to highlight the range of
      clinical presentations and histological features seen in this rare and poorly
      understood condition. Arrhythmogenic right ventricular dysplasia (ARVD) is a
      cardiomyopathy characterized by a normal or mild increase in heart weight with
      right-sided heart dilatation. Typically a proportion of the right ventricular
      muscle is replaced by fat and fibrous tissue. Clinically, the condition is
      characterized by episodes of ventricular tachycardia and global dyskinesia of the
      right ventricle. It may cause ventricular fibrillation and sudden death,
      especially in young persons engaged in strenuous exercise or who experience
      severe emotional outburst. The aetiology of the condition is unknown, although it
      has been noted to show familial clustering in some cases.

PMID- 9264237
TI  - Querulous behavior.

PMID- 9264238
TI  - The role of fractures of neck structures in hanging.

PMID- 9264239
TI  - Reply to Professor Herschel Prins' letter in the April issue.

PMID- 9264241
TI  - Bioorganometallic chemistry--synthesis and antitumor activity of cobalt carbonyl
      complexes.
AB  - The interaction of organometallic compounds with biological systems, generally
      called bioorganometallic chemistry, is receiving increasing interest. We present
      the first part of our studies concerning the biological activity of
      organometallic compounds. Several alkyne-cobalt carbonyl complexes inhibited the
      growth of human melanoma and lung carcinoma cell lines. They are more active than
      uncomplexed dicobalt octacarbonyl, cobalt chloride, or the free ligand. A
      significant difference in potency towards the lung carcinoma cell line was
      observed among the cobalt complexes, indicating that the complexed ligand may
      influence cytotoxic activity. These results suggest that further exploratory work
      with such cobalt-alkyne complexes is warranted.

PMID- 9264240
TI  - Syntheses of novel pyridazinomorphinans by inverse electron demand cycloaddition
      and their binding to mu and kappa receptors.
AB  - A number of novel pyridazinomorphinans have been synthesized by the inverse
      electron demand Diels-Alder reaction of various 3,6-disubstituted 1,2,4,5
      tetrazines with enamines derived from dihydrocodeinone and with codeinone.
      Reduction of some of the pyridazinomorphinans did not furnish the expected
      pyrroloepoxymorphinans; in all cases investigated reductive cleavage of the
      epoxybridge was observed to yield dihydropyridazino- or pyrrolomorphinans. The
      structures of all new compounds were assigned by the spectral data, that of the
      cycloadduct of codeinone was additionally verified by X-ray crystallography.
      Compounds 5a, 8, 11a and 16 have been evaluated for their affinity at mu and
      kappa opioid receptors in radioligand binding assays. Their ability to inhibit
      [3H]DAMGO binding at mu and [3H]U 69.593 binding at kappa receptors, respectively
      as compared to codeine has been found to be lower.

PMID- 9264242
TI  - Structure-activity relationship studies of CNS agents, Part 32: Effect of
      structural modifications in 1-arylpiperazine derivatives on alpha(1) 
      adrenoreceptor affinity.
AB  - The alpha(1)-adrenergic and 5-HT1A serotonergic receptor affinities of a series
      of 1-arylpiperazines are presented. The role of the spacer and the influence of
      the terminal substituents on the alpha(1)-adrenoreceptor affinity and the 5
      HT1A/alpha(1) receptor selectivity are discussed.

PMID- 9264244
TI  - Synthesis of vinca alkaloids and related compounds. Part 84. Sulfonamide
      derivatives of some vinca alkaloids with cardiovascular activity.
AB  - (+)-Vincamine (1) and (+)-vinpocetine (2) were chlorosulfonylated and the
      resulting sulfonyl chloride isomers (3-6) were transformed into sulfonamides (7
      10). The ester group of sulfonamides was modified by selective hydrolysis and
      transesterification. Apovincaminol derivatives (14-16) were also prepared by
      reduction. In addition to the known cerebrovascular effects of the unsubstituted
      compounds (1,2) sulfonamides also show a significant peripheral vasodilator
      effect.

PMID- 9264243
TI  - Aza-analogs of 8-styrylxanthines as A2A-adenosine receptor antagonists.
AB  - In the present study we synthesized aza-analogs of 8-styrylxanthines, in which
      the ethenyl bridge is replaced by an imine, amide, or azo function, in order to
      investigate structure-activity relationships of the 8-substituent of A2A
      selective xanthine derivatives. Thus, various 8-substituents were combined with
      theophylline or caffeine, respectively, and affinities of the novel compounds for
      adenosine A1- and A2a-receptors were determined and compared with those of
      analogous 8-styrylxanthine derivatives. 8-(Benzylideneamino)caffeine derivatives
      exhibited high affinity and selectivity for A2A-adenosine receptors, but were
      unstable in aqueous buffer solution at physiological pH values. 8
      (Phenylazo)caffeine derivatives were less potent than corresponding 8
      styrylcaffeine derivatives at adenosine receptors. The most potent azo compound
      of the present series was 8-(m-chlorophenylazo)caffeine (14b) exhibiting a Ki
      value of 400 nM at A2A-adenosine receptors and 20-fold selectivity versus A1
      receptors. Due to the facile synthetic access to 8-(phenylazo)xanthine
      derivatives, which are obtained by coupling of 8-unsubstituted xanthines with
      phenyldiazonium salts, 14b may be an interesting new lead compound for the
      development of more potent and selective A2A-antagonists with azo structure.

PMID- 9264245
TI  - Spatial features of calcium-regulated gene expression.
AB  - A key characteristic of an animal's nervous system is that it can respond to
      brief environmental stimuli with lasting changes in its structure and function.
      These changes are triggered by specific patterns of neuronal electrical activity
      and are manifested as changes in the strength and patterns of synaptic
      connectivity between activated neurons. The biochemical mechanisms that control
      these changes are unclear, but cytoplasmic rises in Ca2+ levels may play a
      critical role, especially in regulating neuronal gene expression for making
      activity-induced synaptic changes permanent. Recently, two reports have explored
      the spatial features by which activity-induced rises in Ca2+ levels activate
      transcription factors and gene expression. The reports suggest that Ca2+ influx
      acts both locally at the synapse and distantly within the nucleus to regulate
      transcription factors and gene expression. The results also show that regulatory
      elements within genes can respond differentially, depending on spatial
      differences in intracellular Ca2+ rises. These reports suggest new spatial
      mechanisms by which Ca(2+)-dependent gene expression could contribute to activity
      dependent synaptic changes.

PMID- 9264246
TI  - Why are Hox genes clustered?
AB  - The evolutionarily conserved genomic organization of the Hox genes has been a
      puzzle ever since it was discovered that their order along the chromosome is
      similar to the order of their functional domains along the antero-posterior axis.
      Why has this colinearity been maintained throughout evolution? A close look at
      regulatory sequences from the mouse Hox clusters suggests that enhancer sharing
      between adjacent Hox genes may be one reason. Moreover, characterizing the
      activity of one of these mouse enhancers in Drosophila illustrates that despite
      many similarities, not all Hox clusters are built in the same way.

PMID- 9264247
TI  - Looking into the sea urchin embryo you can see local cell interactions regulate
      morphogenesis.
AB  - The transparent sea urchin embryo provides a laboratory for study of
      morphogenesis. The calcareous endoskeleton is formed by a syncytium of mesenchyme
      cells in the blastocoel. The locations of mesenchyme in the blastocoel, the size
      of the skeleton, and even the branching pattern of the skeletal rods, are
      governed by interactions with the blastula wall. Now Guss and Ettensohn show that
      the rate of deposition of CaCO3 in the skeleton is locally controlled in the
      mesenchymal syncytium, as is the pattern of expression of three genes involved in
      skeleton formation. They propose that short range signals emanating from the
      blastula wall regulate many aspects of the biomineralization process.

PMID- 9264248
TI  - Dueling orphans--interacting nuclear receptors coordinate Drosophila
      metamorphosis.
AB  - At least seven orphan members of the nuclear receptor superfamily are
      transcriptionally regulated by the steroid hormone ecdysone and expressed during
      the onset of Drosophila metamorphosis. A recent paper provides functions for two
      of these receptors, E75B and DHR3, through trans-regulation and
      heterodimerization. DHR3 appears to function as a switch that defines the
      transition from a late larva to a prepupa, and E75B functions as a timer that
      modulates this transition. This study provides a biological function for orphan
      receptor interactions during development.

PMID- 9264249
TI  - Epithelial differentiation in Drosophila.
AB  - Our understanding of epithelial development in Drosophila has been greatly
      improved in recent years. Two key regulators of epithelial polarity, Crumbs and
      DE-cadherin, have been studied at the genetic and molecular levels and a number
      of additional genes are being analyzed that contribute to the differentiation of
      epithelial cell structure. Epithelial architecture has a profound influence on
      morphogenetic movements, patterning and cell-type determination. The combination
      of embryological and genetic/molecular tools in Drosophila will help us to
      elucidate the complex events that determine epithelial cell structure and how
      they relate to morphogenesis and other developmental processes.

PMID- 9264250
TI  - Epithelial stem cells.
AB  - New molecular markers for epidermal stem cells have enabled their isolation both
      in vitro and from the epidermis lying between hair follicles. Micro-dissection
      experiments have localised a second population of stem cells within hair
      follicles. Epidermal stem cells have a patterned distribution in vivo. The
      patterning can be reconstituted in vitro, showing that it is generated by
      interactions between keratinocytes and that the differentiation of epidermal stem
      cells is regulated by signals from other keratinocytes. Recent evidence from
      transgenic mice suggests that stem cell behaviour in the gut may be regulated by
      similar cell-cell interactions in vivo. Candidate genes for mediating these
      interactions are the homologues of Drosophila cell fate patterning genes such as
      Notch and Wingless and the Cadherin family of cell-cell adhesion molecules. The
      roles of stem cells and of mutations of the Patched gene in epithelial
      carcinogenesis are discussed.

PMID- 9264251
TI  - Regulation of gene expression in developing epidermal epithelia.
AB  - Skin is one of the most thoroughly studied epithelia and can be used as a model
      for transcriptional control of epithelial differentiation. In particular, the
      stages of epidermal development and differentiation from a simple epithelium are
      well characterized. Temporal gene expression during development can be used to
      assign roles for transcription factors in epidermal differentiation. Approaches
      to understanding transcriptional regulation in epidermis include extensive
      promoter analysis and expression studies, in some cases coupled to functional
      studies. This work has not produced any consensus about the importance of any
      particular factor or class of factors in epidermal specification. There is, as
      yet, nothing similar to the myo D family of tissue-specific and cell-type
      determining factors in epidermis. These studies, however, have revealed much
      about control of the differentiation process in epidermis. Most recently, there
      has been a suggestion that epithelial transcription can be influenced directly by
      the status of the adhesion complexes at the cell surface, providing a direct link
      between one of the distinguishing features of the epithelial state and gene
      transcription.

PMID- 9264252
TI  - Molecular aspects of the epithelial phenotype.
AB  - Epithelia can be defined morphologically as tissues that line surfaces, and
      ultrastructurally with reference to their cells' apico-basal polarity and
      possession of specific cell-cell junctions. Defining the epithelial phenotype at
      a molecular level is more problematic--while it is easy to name proteins (e.g.
      keratins) expressed by a 'typical' epithelium, no known molecules are expressed
      by every epithelium but by no other tissues. Cells can differentiate to and from
      the epithelial state as part of normal development, as a response to disease or
      when manipulated in culture. Many factors (matrix components, adhesion molecules,
      growth factors, transcription factors) have been identified that can trigger
      these transitions of phenotype in specific cases, but to date no general master
      regulators of the epithelial state have been found. The epithelial state may
      therefore be controlled by multiple regulatory genes so that there is no single
      molecule responsible for all of the diverse types of epithelium that exist in
      higher animals.

PMID- 9264253
TI  - The epithelial cell default-phenotype hypothesis and its implications for cancer.
AB  - The expression of epithelial cell adhesion and cytoskeletal genes is orchestrated
      by an apparently unique set of rules. No tissue-specific transactivator proteins
      have been found to drive them; only ubiquitous factors are utilized. In non
      epithelial cells, they are actively repressed. Moreover, it was recently found
      that a single protein (adenovirus E1a) coordinately represses non-epithelial
      genes while inducing epithelial genes. A simple model is offered to explain how
      epithelial gene expression is coordinated. Under this model, the epithelial cell
      gene expression program is a transcriptional 'default'; that is, it occurs in the
      absence of tissue-specific transactivation. Conversion to this default requires
      only that mesenchymal transactivators are not expressed, or that central
      'integrator' proteins are inactive. In their absence, mesenchymal gene expression
      cannot occur. Moreover, because the repressors cease to be expressed, the
      epithelial genes are induced. Oncogenes generally cause the breakdown of the
      epithelial phenotype--generating carcinomas--so genes such as E1a that cause
      epithelial conversion may prove useful for both understanding and controlling
      cancer.

PMID- 9264254
TI  - Epithelial apoptosis.
AB  - Apoptosis is an essential part of the normal cellular phenotype repertoire. In
      the absence of appropriate survival factors, apoptosis is activated through
      specific signalling cassettes. Epithelia form distinctive three-dimensional
      cohesive structures that depend on adhesive interactions in order for these
      tissues to carry out their specialised roles, such as secretion and reproduction.
      The cellular programme that triggers apoptosis in epithelial cells has not yet
      been shown to differ form that in other cell types, yet the unique
      characteristics of epithelia endow them with specific determinants for survival.
      In particular, cell-matrix and cell-cell interactions are required to prevent
      entry of epithelial cells into apoptosis, and soluble factors that have profound
      effects on epithelia, such as steroid hormones or hepatocyte growth factor, also
      influence their survival. The regenerative capacity of certain epithelia is
      controlled by intrinsic expression of survival genes within stem cell
      populations, and may regulate the susceptibility of different epithelial tissues
      to undergo carcinogenesis.

PMID- 9264255
TI  - Morphogens and pattern formation.
AB  - Morphogen gradient theories have enjoyed considerable popularity since the
      beginning of this century, but conclusive evidence for a role of morphogens in
      controlling multicellular development have been elusive. Recently, work on three
      secreted signalling proteins. Activin in Xenopus, and Wingless and Dpp in
      Drosophila, has strongly suggested that these proteins function as morphogens. In
      order to define a factor as a morphogen, it is necessary to show firstly, that it
      has a direct effect on target cells and secondly, that it affects the development
      of target cells in a concentration-dependent manner. With these criteria in mind,
      the evidence available for a variety of proposed morphogens is discussed. While
      the evidence is not conclusive in most of the cases considered, there is a strong
      case in favour of the three proteins mentioned above, which suggests that
      morphogens are potentially of general importance in controlling the development
      of multicellular organisms.

PMID- 9264256
TI  - Selective compartments for resistant microorganisms in antibiotic gradients.
AB  - The development of bacterial resistance to antibiotics is one of the best
      documented examples of contemporary biological evolution. Variability in the
      mechanisms of resistance depends on the diversity of genotypes in the huge
      bacterial populations, and also on the diversity of selective pressures that are
      produced along the antibiotic concentration gradients formed in the highly
      compartmentalized human body during therapy. These antibiotic gradients can be
      conceived as comprising selective compartments, each one of them defined as the
      concentration able to select a particular genetic variant. In vitro experimental
      models confirm that some antibiotic resistant variants are selected only at
      certain selective concentrations of antibiotics. The correspondence between
      selective compartments and selectable variants could offer a way of describing
      more accurately the antibiotic selective landscapes and for taking measures to
      prevent the development of a major threat to the future of modern medicine.

PMID- 9264257
TI  - Initial closure of the mesencephalic neural groove in the chick embryo involves a
      releasing zipping-up mechanism.
AB  - According to a traditional viewpoint, initial closure of the anterior neural
      groove involves bilateral elevation of the edges of the neural plate, flattening
      of the midline area, subsequent convergence of the dorsal neural folds, and
      finally adhesion and fusion of the medial fold edges. In a transverse view, the
      shape of the neural groove thereby changes from V > U > toppled C > O. This
      sequence implicates that the neural groove is wide almost from its inception. In
      the present study, a new mechanism of initial closure is proposed, based on
      observations in living chick embryos and on light and scanning electron
      microscopic observations during neurulation in the presumptive mesencephalic
      region. The medial part of the neural plate invaginates in ventral direction. The
      walls of the arising neural groove appose, beginning in the depth, and make
      subsequent contact. During continued invagination the neural walls extend in
      ventral direction, the apposition/contact zone shifts in dorsal direction up to
      the neural folds and the neural walls separate ventrally, resulting in the
      incipient neural tube lumen. The mechanism is best compared with a zipping-up
      releasing model. In a transverse view, the shape of the neural groove changes
      from V > Y > I > O. While, according to the traditional view, the neural folds
      have to converge from a distance in order to contact each other, in the present
      mechanism the walls and folds are sequentially in contact by the ventro-dorsal
      zipping-up mechanism, thereby avoiding the possibility of mismatch of the neural
      folds. The above process is initiated over a considerable longitudinal distance
      along the neural plate, but only at the mesencephalic level does the dorsal shift
      of the contact zone become complete. At other levels of the neuraxis, the contact
      zone releases prematurely and the neural walls become widely separated well
      before their dorsal neural folds are in contact. These folds have to converge,
      therefore, in order to close, but their matching is facilitated by the alignment
      of the previously contacted neural folds at the mesencephalic level as well as by
      guidance underneath the vitelline membrane.

PMID- 9264258
TI  - Proliferation and differentiation of smooth muscle cell precursors occurs
      simultaneously during the development of the vessel wall.
AB  - Formation of the blood vessel wall depends on the recruitment, proliferation, and
      differentiation of smooth muscle cell (SMC) precursors. The temporal events
      associated with the onset of expression of several SMC proteins have been well
      characterized in mouse and avian species. However, the timing of cell
      proliferation during this process has not been explored. More importantly, it has
      not been clear whether commitment to the smooth muscle pathway precludes
      proliferation during development. In the present study, we have determined the
      kinetics of replication in developing chick aortae between days 2.5 and 19 and
      have correlated these data with the expression of various SMC differentiation
      markers. We found that proliferation of aortic SMC precursors occurs in two
      waves; an early phase of rapid proliferation (15-17%; between days 4 and 12), and
      a second phase, when replication was reduced to less than 5% (days 16 to
      hatching). Proliferation of SMC during the first wave occurred concomitantly with
      the progressive accumulation of SMC contractile proteins, such as SM alpha-actin,
      calponin, myosin heavy chain, and the 1E12 antigen. We also found that the
      relative proliferation capacity within each compartment of the vessel wall, ie.,
      intima, media, and adventitia varies throughout development. Approximately, 55
      63% of all replicating cells were found in the tunica adventitia from days 6 to
      12, whereas 35% were found in the tunica media (tunica media:adventitia = 1:2).
      This ratio was inverted after day 12, when most of the replicating cells were
      located in the tunica media (tunica media:adventitia = 2:1). In addition, we
      observed a ventral-to-dorsal gradient in the proliferation of SMC precursors
      between days 2.5 and 5. The ventral-to-dorsal proliferation gradient was similar
      to the previously described differential expression of two early SMC markers:
      alpha-actin and the 1E12 antigen. These data support the concept that a polarity
      exists either in the pool of SMC precursors or, in expression of factors that
      regulate recruitment of presumptive SMC.

PMID- 9264259
TI  - TGF-alpha, EGF, and their cognate EGF receptor are co-expressed with desmin
      during embryonic, fetal, and neonatal myogenesis in mouse tongue development.
AB  - The developing mouse tongue provides a model for discrete patterns of
      morphogenesis during short periods of embryonic development. Occipital somite
      derived myogenic cells interact with cranial neural crest-derived ecto
      mesenchymal cells to form the musculature of the tongue. The biochemical signals
      that control close range autocrine and/or paracrine signaling processes required
      to establish the fast-twitch complex tongue musculature are not known. The
      present study was designed to test the hypothesis that desmin, epidermal growth
      factor (EGF), and transforming growth factor-alpha (TGF alpha) and their cognate
      receptor, epidermal growth factor receptor (EGFr), are co-expressed during tongue
      myogenesis and define specific developmental stages of tongue muscle cell
      differentiation. To test this hypothesis, we performed studies to analyze the
      timing, position, and concentration of desmin, TGF alpha, EGF, and EGFr from
      embryonic day 9 (E9) through birth in Swiss Webster mouse tongue development.
      Desmin, TGF alpha, EGF, and EGFr co-localized to cells of myogenic lineage in the
      four occipital somites and subsequently in myoblasts and myotubes from E9 through
      E17. By newborn stage, desmin is localized to discrete regions in myofibers
      corresponding to Z-line delimiting sarcomeres, and A-band within sarcomeres;
      immunostaining for desmin, TGF alpha, and EGF persisted in differentiated
      myotubes and striated skeletal muscle. Desmin increased from 0.01% at E11 to
      0.51% of the total protein by E17 and at birth. Concomitantly, the patterns and
      increases in TGF alpha, EGF, and EGFr showed significant increases during the
      same developmental period. The temporal and positional co-localization of TGF
      alpha, EGF, and EGFr support the hypothesis that autocrine and paracrine
      regulation of desmin by actions of growth factor ligand and receptor defines
      critical stages of tongue myogenesis.

PMID- 9264260
TI  - Localization of basement membrane-associated protein isoforms during development
      of the ocular surface of mouse eye.
AB  - The developmental localization patterns of collagen type IV alpha1-5 chains,
      laminin-1, laminin-5, and laminin alpha2 chain were analyzed in the embryonic
      mouse eye using isoform specific antibodies and immunofluorescence microscopy.
      Laminin-1 isoform and alpha1-2(IV) were ubiquitously expressed along the ocular
      surface basement membranes at a very early stage of eye development. Alpha3-5(IV)
      were first detected at later stages of development, and exhibited a variable
      distribution pattern along the ocular surface basement membrane. In contrast,
      expression of the laminin alpha2 chain was restricted to the conjunctival
      basement membrane, and was first detected during the same developmental period in
      which keratin K4-positive, differentiated conjunctival epithelial cells were
      observed. Although laminin-5 was uniformly expressed along the adult ocular
      surface basement membrane, during embryogenesis it was first incorporated into
      the conjunctival basement membrane structure. These data suggest that some of the
      laminin isoforms, including laminin alpha2 and laminin-5, may play a role in the
      formation of a conjunctival-type basement membrane. The temporal relationship
      between the localization of these molecules to the conjunctival basement membrane
      and the appearance of differentiated conjunctival epithelial cells suggests a
      role for external influence on the differentiation pathways of ocular surface
      epithelium.

PMID- 9264261
TI  - Parallel expression of Sox9 and Col2a1 in cells undergoing chondrogenesis.
AB  - To assess the role of the transcription factor Sox9 in cartilage formation we
      have compared the expression pattern of Sox9 and Col2a1 at various stages of
      mouse embryonic development. Expression of Col2a1 colocalized with expression of
      Sox9 in all chondroprogenitor cells. In the sclerotomal compartment of somites
      the onset of Sox9 expression preceded that of Col2a1. A perfect correlation was
      also seen between high levels of Sox9 expression and high levels of Col2a1
      expression in chondrocytic cells. However, no Sox9 expression was detected in
      hypertrophic chondrocytes; only low levels of Col2a1 RNA were found in the upper
      hypertrophic zone. Coexpression of Sox9 and Col2a1 was also seen in the
      notochord. At E11.5 Sox9 expression in the brain and spinal neural tube was more
      widespread than that of Col2a1 although at E14.5 Sox9 and Col2a1 transcripts were
      colocalized in discrete areas of the brain. Distinct differences between Sox9 and
      Col2a1 expression were observed in the otic vesicle at E11.5. At E8.5, expression
      of Sox9 but not of Col2a1 was seen in the dorsal tips of the neural folds and
      after neural tube closure also in presumptive crest cells emigrating from the
      dorsal pole of the neural tube. No Col2a1 expression was detected in gonadal
      ridges in which high levels of Sox9 expression were detected. Together with our
      previous results showing that the chondrocyte-specific enhancer element of the
      Col2a1 gene is a direct target for Sox9, these results suggest that Sox9 plays a
      major role in expression of Col2a1. The correlation between high expression
      levels of Sox9 and high expression levels of Col2a1 in chondrocytes suggests the
      hypothesis that high levels of Sox9 are needed for full expression of the
      chondrocyte phenotype; lower levels of Sox9 such as in neuronal tissues which are
      also associated with lower expression levels of Col2a1 would be compatible with
      other cell specifications.

PMID- 9264262
TI  - Basic fibroblast growth factor (FGF-2) induced transdifferentiation of retinal
      pigment epithelium: generation of retinal neurons and glia.
AB  - In the present study we report that basic fibroblast growth factor (bFGF, FGF-2)
      promotes the transdifferentiation of Xenopus laevis larval retinal pigment
      epithelium (RPE) into neural retina. Using specific antibodies we have examined
      the cellular composition of the regenerated retinal tissue. Our results show
      that, in addition to retinal neurons and photoreceptors, glial cells were also
      regenerated from the transdifferentiated RPE. These results were specific to FGF
      2, since other factors that were tested, including acidic FGF (aFGF, FGF-1),
      epidermal growth factor (EGF), laminin, ECL, and Matrigel, exhibited no activity
      in inducing retinal regeneration. These results are the first in amphibians
      demonstrating the functional role of FGF-2 in inducing RPE transdifferentiation.
      Transplantation studies were carried out to investigate retinal regeneration from
      the RPE in an in vivo environment. Sheets of RPE implanted into the lens-less
      eyes of larval hosts transformed into neurons and glial cells only when under the
      influence of host retinal factors. In contrast, no retinal transdifferentiation
      occurred if the RPE was implanted into the enucleated orbit. Taken together,
      these results show that the amphibian RPE is capable of transdifferentiation into
      neuronal and glial cell-phenotypes and implicate FGF-2 as an important factor in
      inducing retinal regeneration in vitro.

PMID- 9264263
TI  - Differential expression of galectin-1 and galectin-3 during first trimester human
      embryogenesis.
AB  - Development of complex organisms requires specific temporospatial differentiation
      and expression of the correct phenotype through activation of a variety of genes.
      Galectins are mammalian lectins able to interact with various extracellular
      matrix glycoconjugates and have been implicated in several biological events
      including cell attachment, differentiation, apoptosis, embryogenesis, and cancer
      invasion and metastasis. In this study, we have examined the expression of
      galectin-1 and galectin-3 during human first trimester embryogenesis using
      immunohistochemistry and Western blotting. Variable amounts of galectin-1 and
      galectin-3 were detected in all tissue protein extracts. Galectin-1 expression
      was demonstrated in the connective tissue and derived tissues such as smooth and
      striated muscle cells, and in some epithelia, such as in the basal layers of the
      skin after 14 weeks and in the epithelial cells of the gonads. Galectin-3 was
      detected mainly in epithelia, such as the skin, epithelial lining of the
      digestive and respiratory tract, and urothelium and excretory tubes of the
      kidney, but also in the myocardial cells, in the peripheral and preossifying
      hypertrophic chondrocytes, and in the notochord and in the liver. Our study
      constitutes the first demonstration of galectin-1 and galectin-3 during human
      embryogenesis. The differential expression of these two lectins suggests that
      they could participate in the complex processes of tissue differentiation.

PMID- 9264265
TI  - Expression of ALK-1, a type 1 serine/threonine kinase receptor, coincides with
      sites of vasculogenesis and angiogenesis in early mouse development.
AB  - ALK-1 is a type I serine/threonine kinase receptor for members of the TGF-beta
      superfamily of growth factors; its endogenous ligand is not known. In this study,
      we have analyzed the temporal and spatial expression pattern of ALK-1 mRNA in
      mouse embryos from the one-cell zygote until 12.5 dpc using RT-PCR and in situ
      hybridization. ALK-1 mRNA was first detected in the embryo at 6.5 dpc. From 7.5
      8.5 dpc expression was highest at sites of vasculogenesis in both the embryonic
      and extraembryonic part of the conceptus, in trophoblast giant cells, and in the
      endothelial lining of the blood vessels in the decidua. From 9.5-12.5 dpc, ALK-1
      was found to be expressed in several different tissues and organs, but was
      highest in blood vessels, mesenchyme of the lung, submucosal layer of the stomach
      and intestines, and at specific sites of epithelial-mesenchymal interactions. Its
      expression pattern suggests that ALK-1 is a type I receptor for TGF-beta1 in the
      developing mouse.

PMID- 9264264
TI  - lim6, a novel LIM homeobox gene in the zebrafish: comparison of its expression
      pattern with lim1.
AB  - A novel LIM class homeobox gene, lim6, was isolated from a zebrafish embryonic
      cDNA library. The encoded protein shares a high degree of sequence similarity
      with the previously described Lim1 and Lim5 proteins. This study compares the
      spatial and temporal expression pattern of the closely related lim6 and lim1
      genes during early embryogenesis. Generally, lim6 mRNA was found at rather low
      amounts compared to lim1 mRNA. At the shield stage, lim6 mRNA, similar to lim1
      mRNA, was predominantly expressed in the shield. Lim6 was transiently expressed
      in a restricted region of the anterior neural plate at the bud stage, distinct
      from the expression of lim1 in the notochord and the pronephros and pronephric
      ducts. During the segmentation period, the lim6 gene started to be expressed in
      single cells in the spinal cord, followed by a gradually increasing wide-spread
      expression throughout the CNS. During this stage, lim1 mRNA disappeared in the
      notochord and pronephric ducts and was found in the pronephroi and single cells
      in the CNS. In 24 hr embryos, lim6 and lim1 were expressed in the fore-, mid-,
      and hindbrain and the spinal cord, except that lim1 mRNA was limited to two small
      domains in the telencephalon, whereas lim6 mRNA was widely expressed in this
      region. A comparison of expression of lim1 and lim6 and of the previously
      characterized lim5 show that, in spite of close sequence similarity, distinct
      expression patterns imply nonredundant functions for each member of this group of
      genes.

PMID- 9264266
TI  - Cases and controls from different settings: ideals and practicalities.

PMID- 9264267
TI  - Height, body weight, and risk of prostate cancer.
AB  - Using data from the Health Professionals Follow-Up Study, we prospectively
      examined the relationships between height, body mass index, waist and hip
      circumferences, and risk of total and advanced (extraprostatic and metastatic)
      prostate cancer. In addition, we assessed adiposity during childhood,
      adolescence, and early, middle, and late adulthood using pictograms in relation
      to prostate cancer risk. Between 1986 and 1994, 1,369 cases of prostate cancer
      (excluding stage A1) were confirmed in 47,781 men. Adult body mass index and
      waist and hip circumferences were not appreciably related to risk of total
      prostate cancer or advanced prostate cancer. In contrast, preadult (age 10)
      obesity assessed in 33,336 men in 1988 was prospectively related to lower risk of
      advanced [relative risk (RR) = 0.72 with 95% confidence interval (CI) = 0.47
      1.10, between high and low quintiles; P(trend) = 0.06] and metastatic prostate
      cancer (RR = 0.38 with 95% CI = 0.19-0.77; P(trend) = 0.004). For the advanced
      lesions, an association was observed with height (RR = 1.68 with 95% CI = 1.16
      2.43 for men 74 inches or taller, relative to men 68 inches or shorter; P(trend)
      = 0.01). In an analysis limited to particularly aggressive forms of prostate
      cancer, i.e., cases found to be metastatic at time of diagnosis between 1988 and
      1994 after a negative digital rectal examination in 1988, we found that obesity
      at ages 5 and 10 had a strong inverse association (RR = 0.16 with 95% CI = 0.05
      0.54, between high and low quintiles at age 10) and that tallness had a strong
      direct association with risk of metastatic disease (RR = 2.29 with 95% CI = 1.04
      5.05, for height > or = 74 inches versus < or = 68 inches). Our findings suggest
      that the preadult hormonal milieu, as reflected in attained height and childhood
      obesity, may have a strong influence on prostate carcinogenesis.

PMID- 9264268
TI  - Identifying and recruiting healthy control subjects from a managed care
      organization: a methodology for molecular epidemiological case-control studies of
      cancer.
AB  - Case-control studies with stringent matching criteria require large pools of
      healthy subjects from which to select matched controls. This paper describes a
      successful method of identifying a large pool of potential control subjects to
      participate in two molecular epidemiological case-control studies of lung cancer,
      each enrolling 400 case subjects and 400 control subjects. These studies are not
      population based, and the study base is not well-defined. Therefore, potential
      control subjects are being identified and recruited through 20 area clinic sites
      of a large multispecialty health maintenance organization. Because the research
      focus is driven by genetic hypotheses and we are controlling for multiple smoking
      related variables, representativeness is of lesser concern. To identify potential
      control subjects, a one-page questionnaire is distributed to patients in the
      waiting room to assess contact information as well as data relevant to the case
      control matching process. An average of 2,228 questionnaires are returned monthly
      toward a target pool of 40,000; of these, 59% of the respondents fulfill
      eligibility criteria as a control subject for one of the studies and are not
      averse to being contacted in the future for the purpose of research. When
      compared to former smokers and never smokers, current smokers in the control
      population were least likely to refuse further contact. A collaborative
      arrangement with a managed care organization offers a feasible mechanism through
      which researchers can access a large, ethnically diverse population of potential
      control subjects.

PMID- 9264269
TI  - Meat intake, heterocyclic amines, and risk of breast cancer: a case-control study
      in Uruguay.
AB  - To study the effects of meat intake, including heterocyclic amine exposure, on
      the risk of breast cancer, we conducted a hospital-based case-control study
      involving 352 patients with breast cancer and 382 controls. A strong effect of
      red meat, total meat, beef, fried meat, and heterocyclic amine exposure was
      found, after controlling for potential confounders. The odds ratio for the
      highest quartile of 2-amino-3-methylimidazo [4,5-f]quinoline exposure was 3.34
      (95% confidence interval 1.85-6.02). According to these results, meat intake and
      chemicals formed during the cooking process appear to be strong risk factors in
      human breast carcinogenesis.

PMID- 9264270
TI  - Expression of p53 protein in actinic keratosis, adjacent, normal-appearing, and
      non-sun-exposed human skin.
AB  - Nonmelanoma skin cancer, including both squamous cell carcinoma and basal cell
      carcinoma, is a significant and increasing health problem in the United States.
      The precursor lesion of cutaneous squamous cell carcinoma, actinic keratosis
      (AK), is a major risk factor for nonmelanoma skin cancer, and it is also a marker
      of long-term sun exposure. AKs themselves can serve as biomarkers in
      chemopreventive studies, but in addition, they may contain phenotypic and genetic
      alterations that are related to the process of UV-induced skin carcinogenesis.
      One of these alterations, the tumor suppressor gene p53, is altered early in UV
      induced skin carcinogenesis in humans. p53 protein expression was measured by
      immunohistochemistry in biopsies from AKs, tissue immediately adjacent to AKs (AK
      adjacent), normal-appearing upper medial arm skin, and non-sun-exposed skin from
      19 subjects. There was a significant difference and a progressively increasing
      mean p53 labeling index in total epidermis (basal and suprabasal layers) between
      upper medial arm skin (0.9 +/- 1.8%) and AK-adjacent (12.1 +/- 14.4%; P = 0.0004)
      and between AK (27.7 +/- 21.3%) and AK-adjacent skin (P = 0.04), whereas upper
      medial arm skin was marginally different from non-sun-exposed skin (0.1 +/- 0.2;
      P = 0.05). This pattern of p53 expression was also seen when epidermis was
      separated into basal and suprabasal layers. We conclude that epidermal p53
      protein expression is associated with histological evidence of chronic sun
      damage.

PMID- 9264271
TI  - Serum beta-carotene level, arsenic methylation capability, and incidence of skin
      cancer.
AB  - To elucidate the associations of arsenic-induced skin cancer with serum beta
      carotene level and arsenic methylation capability, a total of 654 residents of
      age 30 or older were recruited from three arseniasis-hyperendemic villages in
      Taiwan and regularly examined for skin lesions during the follow-up period. There
      were 33 cases affected with newly diagnosed skin cancer during the follow-up,
      giving an incidence of 14.74 per 1000 person-years. Although most study subjects
      had stopped consuming high-arsenic artesian well water more than 20 years ago,
      the risk of skin cancer was found to increase significantly with cumulative
      arsenic exposure before the cessation of drinking artesian well water in a dose
      response relationship. Frozen serum samples collected at the recruitment from
      newly developed skin cancer cases and matched controls were tested for beta
      carotene levels by high-performance liquid chromatography. Frozen urine samples
      of these subjects were examined by high-performance liquid chromatography to
      speciate arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMA), and
      dimethylarsinic acid and then quantitated by hydride generator combined with
      atomic absorption spectrometry. Skin cancer cases had a significantly lower serum
      level of beta-carotene than matched healthy controls. Although the primary
      methylation capability indexed by the ratio of MMA/(AsIII + AsV) was greater in
      cases than in controls, the secondary methylation capability indexed by the ratio
      of dimethylarsinic acid/MMA was lower in cases than in controls. An elevated
      proportion of MMA in total urinary arsenic level was associated with an increased
      risk of skin cancer. Subjects with a cumulative arsenic exposure of > or = 20.0
      mg/liter-year and a proportion of MMA in total urinary arsenic level >26.7% had a
      multivariate-adjusted odds ratio of developing skin cancer as high as 20.91 (95%
      confidence interval, 2.63-166.5) compared wih those who had a cumulative arsenic
      exposure of <20.0 mg/liter-year and a MMA percentage of < or = 26.7%. Whether the
      association with capability of inorganic methylation is also applied to cancers
      of internal organs, including lung, liver, and urinary bladder, remains to be
      elucidated.

PMID- 9264272
TI  - High dietary omega-6 polyunsaturated fatty acids drastically increase the
      formation of etheno-DNA base adducts in white blood cells of female subjects.
AB  - Lipid peroxidation generates reactive aldehydes such as trans-4-hydroxy-2-nonenal
      and malonaldehyde, which form promutagenic exocyclic DNA adducts in human cells
      and may contribute to diet-related cancers. Using ultrasensitive detection
      methods, analysis of WBC DNA from volunteers in a dietary study revealed that
      high intake of omega-6 polyunsaturated fatty acids increased malonaldehyde
      derived adducts in male and female subjects. In contrast, etheno adducts (1,N6
      ethenodeoxyadenosine; 3,N4-ethenodeoxycytidine) were not elevated in males but
      were, on average, 40 times higher in females, displaying a huge intersubject
      variation in lipid peroxidation-derived DNA damage. Exocyclic DNA adducts are
      promising biomarkers for examining the hypothesis of possible links between
      increased intake of dietary omega-6 polyunsaturated fatty acids, DNA damage, and
      elevated cancer risk for breast, colon, and prostate.

PMID- 9264273
TI  - Predictive value of molecular dosimetry: individual versus group effects of
      oltipraz on aflatoxin-albumin adducts and risk of liver cancer.
AB  - Studies in animals and humans have established serum aflatoxin-albumin adducts as
      biomarkers of exposure to aflatoxin B1 (AFB1), a food-borne hepatocarcinogen. To
      assess the utility of measurements of aflatoxin-albumin adducts to predict risk
      of hepatocellular carcinoma (HCC), 123 male F344 rats were dosed with 20 microg
      of AFB1 daily for 5 weeks after randomization into three groups: no intervention;
      delayed-transient (500 ppm of oltipraz, weeks 2 and 3 relative to AFB1); or
      persistent (500 ppm oltipraz, weeks -1 to 5). Serial blood samples were collected
      from each animal at weekly intervals throughout aflatoxin B1 exposure and assayed
      for levels of aflatoxin-albumin by radioimmune assay. Area under the curve (AUC)
      values for aflatoxin-albumin adducts decreased 20 and 39% in the delayed
      transient and persistent oltipraz intervention groups, respectively, as compared
      to no intervention. Similarly, the total incidence of HCC dropped from 83 to 60%
      (P = 0.03) and 48% (P < 0.01) in these groups. Tumor multiplicity was also
      reduced in the two oltipraz intervention groups, whereas time to HCC was
      increased. Mononuclear cell leukemia, a common neoplasm in F344 rats, was seen in
      39% of the control animals, whereas the two oltipraz interventions reduced
      incidence to 18% (P = 0.05) and 13% (P = 0.01), respectively. Overall, a
      significant association was seen between biomarker AUC and risk of HCC (P =
      0.01). However, when the predictive value of aflatoxin-albumin adducts was
      assessed within treatment groups, there was no association between AUC and risk
      of HCC (P = 0.56). Thus, aflatoxin-albumin adducts can be useful for monitoring
      population-based changes induced by interventions, such as in chemoprevention
      trials, but have limited utility in identifying individuals destined to develop
      HCC. As a consequence, the use of this biomarker in quantitative risk assessment
      should be pursued cautiously.

PMID- 9264274
TI  - A hot spot for p53 mutation in transitional cell carcinoma of the bladder: clues
      to the etiology of bladder cancer.
AB  - Twenty-eight transitional cell carcinomas of the bladder, grade 2 or 3, were
      analyzed for the presence of p53 mutations. Thirteen tumors were found to contain
      14 mutations. These were all base substitution mutations, of which nine were GC-
      >AT transitions (three at CpG sites). The remaining five mutations were
      transversions (three GC-->CG, one GC-->TA, and one AT-->TA). Four of the
      mutations were found at codon 280. A comparison with other studies of bladder
      tumors reveals that a region encompassing codons 280 and 285 represents a hot
      spot for p53 mutation in bladder cancer. The 280/285 hot spot lies within two
      purine-rich sequences that may provide some clues to the identity of potential
      bladder carcinogens. A comparison of mutations from bladder tumors of smokers and
      nonsmokers reveals no significant differences.

PMID- 9264275
TI  - Responsiveness of carotenoids to a high vegetable diet intervention designed to
      prevent breast cancer recurrence.
AB  - Epidemiological studies suggest that a high vegetable diet may reduce risk for
      breast cancer and may also improve prognosis after the diagnosis of breast
      cancer. Circulating carotenoids may serve as a biomarker of vegetable and fruit
      intake, although several factors affect their bioavailability from food sources
      and may influence concentrations. One purpose of this study was to identify
      factors predictive of serum carotenoid, retinol, and alpha-tocopherol
      concentrations in 79 postsurgically resected breast cancer patients at enrollment
      and at 12 months in a feasibility study of a high vegetable, low fat diet
      intervention to reduce risk for cancer recurrence. Another purpose was to
      identify variables associated with change in these serum concentrations 12 months
      after randomization into control and intervention groups. The diet intervention
      (versus control) group had significantly greater increases in carotenoid intakes
      (P < 0.03) and significantly greater increases in serum concentrations of lutein,
      alpha- and beta-carotene, lycopene, and retinol (P < 0.04). Stepwise multiple
      regression revealed the level of dietary intake to be predictive of most serum
      carotenoid concentrations at baseline and 12 months, with additional associations
      between selected micronutrient concentrations and serum cholesterol, body mass
      index, age, percentage of energy intake from fat, and alcohol intake also
      observed at these time points. Intervention group change in serum carotenoid
      concentrations was inversely associated with baseline level, age, and change in
      serum cholesterol concentration and positively associated with change in
      carotenoid and alcohol intake. Circulating carotenoid concentrations are
      responsive to a high vegetable diet intervention, which also included reduced
      dietary fat and increased fiber intakes, to reduce risk for breast cancer
      recurrence.

PMID- 9264276
TI  - Mammography diffusion and trends in late-stage breast cancer: evaluating outcomes
      in a population.
AB  - The purpose of this study was to assess mammography diffusion in a population
      offered an organized breast cancer screening program, using intervals of 1-3
      years, and to evaluate its effect on the late-stage cancer (tumors > or = 3 cm2)
      rates compared to rates in the surrounding community. We measured "ever-use" of
      mammography (1986-1992) among women enrollees of a consumer-controlled health
      care organization (n > or = 60,000/year; ages > or = 40), Group Health
      Cooperative of Puget Sound (GHC). Among these same women and the surrounding
      community (n = > or = 745,000/year), we measured late-stage cancer rates. Using
      unconditional logistic regression, we compared annual rates of ever-use among GHC
      women ages 40-49 and > or = 50 (1986-1992) and late-stage breast cancer (1983/84
      1991/92) among all women. Among all GHC women ages 40 to 49, and 50 years of age
      and older, 67.4 and 82.8%, respectively, ever-used mammography by 1992. By 1992,
      approximately one-third of the mammograms among GHC women occurred in each of the
      three previous years. The rate of late-stage tumors declined significantly in the
      GHC and non-GHC populations among women 50 years of age and older (P < 0.001) but
      not among women ages 40 to 49. In conclusion, implementing a system of automated
      reminders was not sufficient to maximize mammography use in a population.
      Reductions in late-stage disease occurred among women ages > or = 50, even when
      regular" was not synonymous with "annual."

PMID- 9264277
TI  - Transforming growth factor alpha distribution in rectal crypts as a biomarker of
      decreased colon cancer risk in patients consuming cellulose.
AB  - Data from rat experimental carcinogenesis studies indicate that supplemental
      dietary cellulose reduces the incidence of colon cancer. Epidemiology studies
      also indicate that high dietary fiber reduces the risk of colorectal cancer in
      humans. Patients diagnosed with sporadic adenomas were entered into a randomized
      clinical trial to determine if supplemental dietary cellulose would reduce the
      patients' risk for colon cancer. Immunohistochemical staining for transforming
      growth factor alpha (TGF-alpha) was done on biopsies of rectal mucosa taken from
      patients at the time of initial polypectomy and 1 year later. Results were
      evaluated for utility as a surrogate end point biomarker for reduction in colon
      cancer risk. There was a significant decrease in the fraction of the rectal crypt
      cells that stained for TGF-alpha in six of seven of the patients given the
      cellulose supplements but in only one of six of the patients not given cellulose.
      Thus, whether evaluated as a group or in individual patients, there was a
      significant decrease in TGF-alpha in rectal crypts due to cellulose intervention,
      which correlated with the expected ability of supplemental dietary cellulose to
      decrease the risk for colon cancer. Long-term testing of the ability of dietary
      cellulose to reduce adenoma recurrence is under way to validate the use of TGF
      alpha as a surrogate end point biomarker.

PMID- 9264278
TI  - Effect of Helicobacter pylori eradication on subsequent development of cancer
      after endoscopic resection of early gastric cancer.
AB  - Although epidemiological studies strongly suggest an association between gastric
      cancer and Helicobacter pylori infection, there has been no clinical report
      indicating that cure of the infection prevents cancer. We conducted a
      nonrandomized H. pylori eradication trial in patients whose gastric cancer was
      removed by endoscopic resection (ER). We investigated the effect of treatment on
      the histopathology of the gastric mucosa, as well as on the incidence of
      metachronous gastric cancer during the long-term clinical and endoscopic follow
      up. One hundred and thirty-two patients with early gastric cancer underwent ER
      and had H. pylori infection. Sixty-five (group A) were treated with omeprazole
      and antibiotics to eradicate the infection, and 67 (group B) were not. All
      patients were followed for 2 years post ER. After eradication treatment in group
      A, the disappearance of neutrophil infiltration in the antrum and body of the
      stomach was observed as was a decrease of the severity of intestinal metaplasia.
      Endoscopy after ER detected no new gastric cancers in these patients. After 3
      years of follow-up, 6 (9%) of the 67 patients in group B had a new early-stage,
      intestinal-type gastric cancer endoscopically diagnosed. The above results
      suggest that H. pylori eradication may improve neutrophil infiltration and
      intestinal metaplasia in the gastric mucosa and inhibit the development of new
      carcinomas. This finding should be confirmed in a randomized, controlled trial.

PMID- 9264279
TI  - International symposium on the role of lycopene and tomato products in disease
      prevention.

PMID- 9264280
TI  - Diet, nutrition, and genetic susceptibility.

PMID- 9264281
TI  - Formation of a molecular epidemiology group?

PMID- 9264282
TI  - Correspondence re: A. Manetta et al., Beta-carotene treatment of cervical
      intraepithelial neoplasia: a phase II study. Cancer Epidemiol., Biomarkers &
      Prev., 5: 929-932, 1996.

PMID- 9264283
TI  - Correspondence re: J. Shannon et al., Relationship of food groups and water
      intake to colon cancer risk. Cancer Epidemiol., Biomarkers & Prev., 5: 495-502.

PMID- 9264284
TI  - G --> A hypermutation does not result from polymerase chain reaction.

PMID- 9264285
TI  - Synthetic peptide ELISAs for detection of and discrimination between group M and
      group O HIV type 1 infection.
AB  - We developed and evaluated two peptide-based immunoassays to confirm and
      discriminate between group M and group O HIV-1 infection. These assays are based
      on in vitro competition for antibody binding between M and O peptides. The first
      EIA is based on competition between group M and group O gp41 immunodominant
      domains and the second on competition between group O and group M V3 regions of
      gp120. Two panels of sera were used: the first consisted of 109 sera collected
      from 27 group O- and 92 group M-infected patients in whom the HIV isolates had
      been genotyped by sequencing or heteroduplex mobility assay. In this panel, the
      combination of the two assays correctly discriminated 106 samples (100% group O
      and 96.7% group M samples). The second panel, used for the field evaluation of
      the two assays, consisted of 157 samples from HIV-1-infected Cameroonian
      patients, 33 strains having been genotyped. The combination of the two techniques
      in a serogrouping algorithm discriminated 147 of these samples, 74 being HIV-1
      group O and 73 group M. These results always correlated with genotyping results.
      The 10 sera that were not successfully classified by these assays were from early
      seroconverters. Altogether, the two assays clearly differentiated 263 of 276
      (94.9%) samples in the two panels. On the basis of the genotyping results, the
      positive predictive value for group discrimination in the two panels was 100% for
      both GSEIA assays. Our peptide-blocking group-specific EIAs for differentiation
      and confirmation of HIV-1 group M and group O infection are complementary tools
      for epidemiological studies and surveillance of HIV-1 group O strain trafficking.

PMID- 9264286
TI  - Envelope sequence variability and serologic characterization of HIV type 1 group
      O isolates from equatorial guinea.
AB  - Four sera from Equatorial Guinea (EG) suspected to contain antibody against HIV-1
      group O-related viruses were identified on the basis of unusual and differential
      serologic reactivity in selected commercial assays and Western blot. Degenerate
      primers, designed from HIV-1 group O published sequences, were used to PCR
      amplify envelope (env) gene sequences from the suspect EG sera. A complete
      envelope gene sequence from each serum was determined from the overlapping env
      gene fragments. Analysis (PHYLIP package of programs) of Env amino acid sequences
      (translated from nucleotide sequences) indicated that the amino acid sequences
      obtained from EG sera clustered more closely with HIV Env sequences of group O
      compared to group M. The amino acid sequences at the octameric tip of the V3 loop
      were either RIGPLAWY (one isolate), RIGPMAWY (two isolates), or GLGPLAVY (one
      isolate). The V3 tip tetrameric sequence GPLA is represented only once in the
      1995 HIV (Los Alamos) database, but was present in two of our group O-related EG
      samples. The gp41 immunodominant regions (IDR) protein sequences were identical
      for sequences from three of the sera, RLLALETLIQNQQLLNLWGCKGR(K)L(I)VCYTSVK(T)W,
      whereas sequence from the fourth serum contained three changes as noted in
      parentheses. IDR sequences derived from EG sera were unique compared to those
      reported for other HIV-1 group O isolate ANT70, VAU, or MVP5180. Antibody in each
      EG serum directed against the IDR could be detected using synthetic peptides
      comprising sequences from the ANT70 or MVP5180 IDRs, but were most reactive
      against the sequences derived from the samples themselves. Little or no serologic
      reactivity was detected when EG sera were reacted against peptides comprising the
      IDR of HIV-1 group M (subtype B consensus) or HIV-2 (consensus).

PMID- 9264287
TI  - An investigation of the high-avidity antibody response to glycoprotein 120 of
      human immunodeficiency virus type 1.
AB  - The avidity of antibodies for antigens can be measured by determining what
      remains bound after exposing the antibody-antigen complex to a chaotropic agent
      such as urea. This method has been gaining popularity for assessing the immune
      response to the human immunodeficiency virus type 1 (HIV-1) surface glycoprotein
      gp120 (or its counterpart from simian immunodeficiency virus), during natural
      infection or after subunit vaccination. High-avidity antibodies have been
      considered to be a possible correlate of protection. We have examined the avidity
      assay to determine what it, in fact, measures. First, we studied the development
      of the anti-gp120 response in seroconverting individuals. Urea elution reduced
      the polyclonal anti-gp120 titers by 3- to 10-fold. After allowing for the
      consequent reduction in assay sensitivity, there was no obvious change in the
      rate of development of the high-avidity and unfractionated antibody responses.
      Furthermore, in the one individual who developed a strong autologous, virus
      neutralizing response, the appearance of neutralizing antibodies and high-avidity
      antibodies did not coincide. Antibodies to the V3 loop, when present, comprised a
      major fraction of the polyclonal response that survives urea elution. We next
      examined the effect of urea elution on the binding to gp120 of a panel of
      monoclonal antibodies (MAbs). Urea treatment preferentially eluted MAbs to
      discontinuous rather than continuous epitopes, independent of their affinities.
      Furthermore, these patterns of epitope stability were unaltered by the presence
      of polyclonal anti-gp120 antibodies. As most broadly neutralizing anti-gp120
      antibodies recognize discontinuous epitopes, this skewing effect must be taken
      into account when interpreting studies using polyclonal sera.

PMID- 9264289
TI  - Functional B cell abnormalities in HIV type 1 infection: role of CD40L and CD70.
AB  - Early in HIV-1 infection, B cell responses to T cell-dependent antigens are
      impaired. In addition to the receptor-ligand pair CD40/CD40L, CD27/CD70 also
      appears to be involved in T cell-dependent B cell stimulation. We have shown that
      CD70+ B cells are the main producers of Ig when stimulated in a T cell-dependent
      manner, and that CD70 upregulation is dependent on interaction of CD40L on T
      cells with CD40 on B cells. We confirm here that B cells from HIV-infected
      individuals are impaired in T cell-dependent Ig production in vitro. This
      dysfunction could partly be restored by adding allogeneic T cells to the culture.
      In contrast, IgG production induced by CD40 MAb, IgM MAb, and IL-10 was in the
      normal range. In line with this, CD70 upregulation on B cells from HIV-infected
      individuals was impaired after stimulation in vitro by activated T cells but not
      after stimulation with CD40 MAb and IgM MAb. Furthermore, CD40L expression was
      decreased on CD4+ T cells after stimulation in vitro. Finally, CD70 expression on
      freshly isolated B cells from HIV-infected individuals was decreased, and low
      CD70 expression correlated with low IgG production after T cell-dependent
      stimulation. In conclusion, our data strongly suggest that impaired B cell
      responses to T cell-dependent Ag in HIV-1 infection are due to a defect in T
      cells.

PMID- 9264288
TI  - Human immunodeficiency virus glycoprotein-specific CD4+ cytotoxic T lymphocytes
      are involved in two types of cytotoxicity: antigen-specific and cell-cell fusion
      related cell lysis.
AB  - Human immunodeficiency virus (HIV) glycoprotein-specific CD4+ cytotoxic T
      lymphocytes (CTLs) lyse target cells in an MHC-restricted calcium-dependent
      fashion similar to the mechanism used by CD8+ CTLs. However, contact of unprimed
      peripheral blood CD4+ T cells with HIV glycoprotein-expressing cells has been
      shown to cause, in addition to cell-cell fusion, rapid cytolysis that may
      resemble antigen-specific cytotoxicity in the chromium release assay. In this
      study, the ability of glycoprotein-specific CD4+ CTLs to undergo similar fusion
      related cytolysis was examined. The data obtained demonstrate that in addition to
      antigen-specific calcium-dependent cytotoxicity, envelope-specific CD4+ CTLs are
      involved in fusion-related, calcium-independent cytolysis.

PMID- 9264290
TI  - Progressive B cell apoptosis and expression of Fas ligand during human
      immunodeficiency virus type 1 infection.
AB  - HIV-1 infection causes functional defects in T cells. It also leads to a
      progressive reduction in numbers of such cells and both CD4+ and CD8+ cells have
      been reported to undergo apoptosis in culture. A corresponding reduction in B
      cells has not been described, but these cells are also functionally altered, with
      reports of polyclonal activation and hyporesponsiveness to antigenic and
      mitogenic stimuli. Here we investigated B cells from HIV-1-seropositive
      individuals and found that these cells, which are not the target for virus
      infection, died of apoptosis on culturing. We could also confirm previous
      findings that CD4+ cells from HIV-1-infected individuals undergo apoptosis in
      culture. Apoptosis of both B cells and CD4+ cells correlated inversely with CD4
      cell counts. B cells from HIV-1-infected individuals were found to express Fas
      ligand, and the expression of this protein correlated with the levels of
      apoptosis in the same cells. Non-B cells, on the other hand, expressed increased
      levels of Fas but low levels of Fas ligand. These results are in line with
      suggestions that the Fas/Fas ligand pathway may trigger the increased levels of
      apoptosis observed in cells from HIV-1-infected individuals.

PMID- 9264291
TI  - Low production of interferon gamma is related to disease progression in HIV
      infection: evidence from a cohort of 347 HIV-infected individuals.
AB  - A total of 347 HIV-seropositive individuals attending the Department of
      Infectious Diseases at Rigshospitalet in Copenhagen and 110 age- and sex-matched
      healthy controls not at risk for HIV infection were included in this study.
      Interferon gamma (IFN-gamma) production was measured in whole blood of 223 HIV
      seropositive individuals (68 had developed AIDS at enrollment) and 99 healthy sex
      and age-matched controls 4.5 hr after challenge with phytohemagglutinin. HIV
      infected individuals for whom IFN-gamma production was measured were followed
      with a median follow-up time of 2.89 years (range, 0.02-4.54 years) from the date
      of enrollment. Survival analysis was performed considering three different end
      points: (1) a CD4 count below 100 cells/mm3, (2) an AIDS diagnosis defined
      according to the 1993 Centers for Disease Control definition, and (3) death. The
      production of IFN-gamma was highly increased in the blood of HIV-infected
      individuals without AIDS, but decreased in the blood of AIDS patients (both
      compared to controls). In the HIV-infected individuals, the total production of
      IFN-gamma was positively correlated with the number of CD8+ T lymphocytes and
      with the number of CD16+/CD56+ natural killer cells and negatively correlated
      with serum levels of beta2-microglobulin. Low levels of IFN-gamma production were
      associated with an increased risk of experiencing a CD4 count below 100 cells/m3
      and death, analyzed in both univariate analysis and in multivariate analysis
      adjusting for CD4 counts and age. Thus, changes in production of IFN-gamma seem
      to be truly related to the risk for disease progression in HIV infection.

PMID- 9264292
TI  - The metabolic and immunologic effects of short-term thalidomide treatment of
      patients infected with the human immunodeficiency virus.
AB  - Thalidomide therapy has been shown to cause increases in body weight in patients
      with HIV and tuberculosis infections. To examine the nature of this weight gain
      and its immunological correlates in patients with HIV infection, we studied a
      cohort of 13 patients with minimally symptomatic HIV disease. Patients were
      admitted to the Rockefeller University General Clinical Research Center and
      maintained on strict isocaloric diets to achieve weight stabilization before a 14
      day course of thalidomide treatment. Mean percentage weight increase was 3.6% on
      day 14 of thalidomide therapy (p = 0.002). Weight gain was associated with a
      reduction in mean daily urinary nitrogen excretion of 1.81 g (p = 0.017). Resting
      energy expenditure was unaffected by thalidomide. Body composition analysis
      suggested some extracellular fluid retention in the first week of thalidomide
      therapy, followed by an expansion of lean tissue mass during the second week.
      Remarkably, total lymphocyte counts and CD8+ T cell counts increased following
      treatment with the drug from 1578 +/- 185 to 2617 +/- 265 and from 938 +/- 146 to
      1369 +/- 231, respectively. Modest increases in CD4+ T cell counts were also
      observed. Levels of circulating TNF-alpha were not elevated at baseline. A
      significant increase in mean plasma levels of soluble interleukin 2 receptor (sIL
      2r), from 1918 +/- 250 to 3816 +/- 411 pg/ml (p = 0.0022), occurred in response
      to thalidomide, suggesting drug-induced immunological activation. In conclusion,
      thalidomide treatment of patients with HIV infection caused weight gain and lean
      tissue anabolism, even when caloric intake was kept constant. The nature of the
      association between thalidomide treatment-induced metabolic changes and the
      immunomodulatory effects of the drug has yet to be elucidated.

PMID- 9264293
TI  - Brain proton magnetic resonance spectroscopy in HIV-related encephalopathy:
      identification of evolving metabolic patterns in relation to dementia and
      therapy.
AB  - Proton MRS has proved useful in the early diagnosis of HIV-related
      encephalopathy. The modifications of brain metabolism in HIV-related
      encephalopathy can be classified according to different metabolic patterns (Vion
      Dury J et al. CR Acad Sci 1994;317:833-840). The present study describes the
      relative occurrence of these patterns and evaluates their evolution under
      zidovudine treatment. We have examined 112 HIV patients--35 neuroasymptomatic
      patients and 77 patients with ADC (AIDS dementia complex)--with localized proton
      MRS, using the PRESS 135-msec sequence. We have found the same metabolic
      modifications in N-acetylaspartate and choline-containing compounds as described
      in the literature. In addition, 14% of HIV patients with normal MRI displayed
      abnormal MRS, whatever their neurological status. The MRS-added diagnostic value
      in neuroasymptomatic patients reaches 30 %. The occurrence of undifferentiated
      (modification of NAA/Cho ratio only) and Cho (mainly an increase in choline
      signal) patterns is not significantly different in neuroasymptomatic and ADC
      patients. The NAA pattern (mainly a significant loss of NAA) is more frequent in
      ADC patients. Only ADC patients display the double pattern (with a significant
      increase in choline signal and a significant loss of NAA). Quantitated cerebral
      atrophy (bifrontal ratio) is related to the occurrence of NAA loss (in NAA and
      double patterns). An MRS follow-up study of 11 HIV patients showed that the
      clinical outcome was favorable after a 1000-mg/day zidovudine treatment in
      patients displaying an NAA pattern whereas this treatment had no effect on the
      patients displaying the Cho pattern. Consequently, MRS appears to be of great
      interest in predicting responsiveness to antiretroviral drugs and detecting early
      any resistance to treatment.

PMID- 9264294
TI  - Detection of HTLV type I provirus by in situ polymerase chain reaction in
      mouthwash mononuclear cells of HAM/TSP patients and HTLV type I carriers.
AB  - Molecular studies have revealed the presence of HTLV-I provirus DNA in saliva of
      HTLV-I-infected subjects. However, cellular localization has not been determined.
      In the present study, we have used in situ PCR technique to study saliva
      associated cells for localization of HTLV-I proviral DNA. We found that HTLV-I
      proviral DNA was present in the nuclei and cytoplasm of salivary lymphocytes in
      five (71%) of seven HTLV-I-seropositive subjects. The percentage of infected
      cells in positive mouthwash samples ranged from 0.5 to 2%. None of the HTLV-I
      negative patients had HTLV-I provirus in saliva. The localization of HTLV-I
      provirus DNA suggests that salivary lymphocytes can serve as vector for HTLV-I
      infection through saliva.

PMID- 9264295
TI  - HIV type 1 subtype C in Addis Ababa, Ethiopia.

PMID- 9264296
TI  - When seeing isn't believing.

PMID- 9264297
TI  - Propionibacterium endophthalmitis following Molteno tube repositioning.
AB  - PURPOSE: We describe an aphakic patient who developed recurrent Propionibacterium
      acnes endophthalmitis after Molteno tube revision. PATIENT AND METHOD: The
      patient presented with a red painful right eye, decreased vision, and a hypopyon.
      A moderate anterior chamber reaction and mild vitritis were present. Two weeks
      earlier, the patient had undergone Molteno tube repositioning. A diagnosis of P.
      acnes endophthalmitis was made after positive culture of anterior chamber needle
      aspirate. RESULTS: Initially the patient was treated with repeated intraocular
      vancomycin injections, to which the eye "responded poorly." Temporary clearance
      of the infection was achieved after placement of the tube in the subconjunctival
      space. The patient required explantation of the implant to achieve complete
      resolution of the infection. CONCLUSION: Tube reinsertion into the anterior
      chamber resulted in recurrence of the infection. The evaluation of alternative
      therapies of aqueous tube shunt-related endophthalmitis would require a large
      case-controlled series of patients.

PMID- 9264298
TI  - Improved reproducibility of measurements with the nerve fiber analyzer.
AB  - PURPOSE: This study was undertaken to assess and improve the repeatability and
      reproducibility of nerve fiber layer (NFL) measurements using the Nerve Fiber
      Analyzer (NFA I), a scanning laser polarimeter. METHODS: The repeatability of two
      subsequent measurements was determined in 100 healthy eyes. Four methods of image
      evaluation were performed. Polarimetric measurements of retinal NFL were obtained
      along a peripapillary band at the superior and inferior poles of the optic disk
      and analyzed in a one-pixel band of absolute retardation values (method 1) and
      relative to the nasal segment (method 2). Method 3 used measurements obtained in
      a 10-pixel band along the same peripapillary band. Method 4 comprised
      measurements in selected areas outside the peripapillary band, which did not
      contain blood vessels. The repeatability (r) and relative reliability coefficient
      (Rel) were assessed as indices of agreement of repeated measurements. In
      addition, the reproducibility (R) from day to day for methods 3 and 4 was
      assessed by taking 10 images on 10 consecutive days from each of 10 subjects.
      RESULTS: The 95% critical value for r in the superior and inferior segments
      improved from about 30% for methods 1 and 2, to 23% for method 3, and to 11% for
      method 4. For the superior and inferior segments, the fourth method of image
      evaluation yielded a Rel of 98%, as compared with 54% in method 1, 80% in method
      2, and 87% in method 3. The 95% critical value for R was 23% for method 3 but
      only 15% for method 4. CONCLUSIONS: The improved reproducibility of measurements
      has made the NFA I a promising device. An improved reproducibility (smaller limit
      for detecting change) does not necessarily indicate good sensitivity and
      specificity for any instrument. The role of the scanning laser polarimeter in
      clinical practice requires further study.

PMID- 9264299
TI  - Reproducibility of laser Doppler flowmetry in the human optic nerve head.
AB  - PURPOSE: We sought to demonstrate reproducibility of the noninvasive laser
      Doppler flowmetry technique for measuring microvascular hemodynamics of the optic
      nerve head in human subjects. METHODS: Laser Doppler flowmetry was performed by
      four examiners on four human optic nerve heads during multiple sessions.
      Intersubject, interexaminer, intersession, and intrasession variabilities were
      calculated for velocity, blood volume, and blood flow (flux). RESULTS: Initial
      variability of measurements improved after 3 months' experience. The standard
      deviation of the intrasession variation for single readings was 18% of the
      velocity mean value and 24% of the flow (flux) mean value. Based on this, a
      sample size of 17 (power beta = 0.8, alpha = 0.05, paired t test) will
      demonstrate a 10% physiologic change in flux within a session if the average of
      five readings is used before and after the experimental perturbation. The
      intersession variation was 12% and 32% for velocity and flux, respectively.
      Because of this, a larger sample size or additional measurement sessions are
      required for detection of an experimental influence between two sessions. The
      coefficient of variation among subjects for single readings was 7% and 10% for
      velocity and flux, respectively. CONCLUSIONS: Reproducibility of velocity
      measurements is better than reproducibility of flux measurements. After
      experience with the method, laser Doppler flowmetry is sufficiently precise to
      permit feasible studies of human optic nerve head microvascular hemodynamics when
      physiologic perturbations are applied.

PMID- 9264300
TI  - Influence of a dilated pupil on the visual field in glaucoma.
AB  - PURPOSE: The author studied the effects of pupillary dilation on perimetry in a
      group of glaucomatous patients receiving timolol therapy. PATIENTS AND METHODS: A
      prospective study compared the visual fields of 23 patients with primary open
      angle glaucoma of varying severity (mean defect: 3.84; short-term fluctuation:
      1.91; pattern standard deviation [SD]: 3.61; corrected pattern SD: 3.12) before
      and after instillation of phenylephrine 10% using the Octopus 1-2-3 projection
      perimeter (INTERZEAG AG, Schlieren, Switzerland). RESULTS: The mean defect became
      impaired by an average of 3.01 (SD +/- 1.52) dB after administration of
      phenylephrine (p < 0.001). The pattern SD and the corrected pattern SD also
      became impaired with dilation by 1.51 dB (p < 0.01) and 1.73 dB (p < 0.05),
      respectively, after dilation. These changes varied across the visual field. The
      outer zone of the visual field had the greatest impairment after dilation with
      phenylephrine. CONCLUSIONS: Pupillary dilation in patients with glaucoma produces
      a nonuniform decrease in threshold sensitivities that is statistically greater on
      outer zone of the visual field.

PMID- 9264301
TI  - Quantitative estimation of retinal nerve fiber layer height in glaucoma and the
      relationship with optic nerve head topography and visual field.
AB  - PURPOSE: The authors estimated the retinal nerve fiber layer height (RNFLH)
      measurements in patients with glaucoma compared with those in age-matched healthy
      subjects as obtained by the laser scanning tomography and assessed the
      relationship between RNFLH measurements and optic and visual field status.
      METHODS: Parameters of optic nerve head topography and RNFLH were evaluated in
      125 eyes of 21 healthy subjects and 104 patients with glaucoma using the
      Heidelberg Retina Tomograph ([HRT] Heidelberg Engineering GmbH, Heidelberg,
      Germany) for the entire disc area and for the superior 70 degrees (50 degrees
      temporal and 20 degrees nasal to the vertical midline) and inferior 70 degrees
      sectors of the optic disc. The mean deviation of the visual field, as determined
      by the Humphrey program 24-2 (Humphrey Instruments, Inc., San Leonardo, CA,
      U.S.A) was calculated in the entire field and in the superior and inferior
      Bjerrum area. RESULT: Retinal nerve fiber layer height parameters (mean RNFLH and
      RNFL cross-sectional area) were decreased significantly in patients with glaucoma
      compared with healthy individuals. Retinal nerve fiber layer height parameters
      was correlated strongly with rim volume, rim area, and cup/disc area ratio. Of
      the various topography measures, retinal nerve fiber layer (RNFL) parameters and
      cup/disc area ratio showed the strongest correlation with visual field mean
      deviation in patients with glaucoma. CONCLUSION: Retinal nerve fiber layer height
      measures were reduced substantially in patients with glaucoma compared with age
      matched healthy subjects. Retinal nerve fiber layer height was correlated
      strongly with topographic optic disc parameters and visual field changes in
      patients with glaucoma.

PMID- 9264302
TI  - A color Doppler analysis of nifedipine-induced posterior ocular blood flow
      changes in open-angle glaucoma.
AB  - PURPOSE: This pilot study used color Doppler imaging to investigate the effects
      of nifedipine on the posterior ocular blood flow of patients with glaucoma
      progression at normal intraocular pressures. PATIENTS AND METHODS: Eighteen
      patients, 11 men and seven women with a median age of 61.7 years, were imaged
      before and 6 weeks after the initiation of 30 mg of sustained-release nifedipine
      (Procardia XL; produced by either Pfizer or Pratt) daily. RESULTS: There was no
      statistically significant change in the blood velocity of the ophthalmic artery,
      central retinal artery, and main nasal and temporal short posterior ciliary
      arteries after treatment with nifedipine. CONCLUSION: The routine use of
      nifedipine in patients with normal tension glaucoma progression is not supported
      by this study.

PMID- 9264303
TI  - Confocal scanning laser Doppler flowmetry: experiments in a model flow system.
AB  - PURPOSE: We conducted this study toward validating confocal scanning laser
      Doppler flowmetry (SLDF), a new noninvasive technique for measuring retinal and
      optic nerve head hemodynamics. METHODS: We designed a model flow system using a
      glass capillary coupled to a microlitre syringe driven by an infusion pump.
      Eleven capillaries with parallel walls (internal diameters ranging 705 to 25
      microm) were used. The capillaries were perfused with skim milk over a range of
      pump flow rates. At each flow rate, measurements were made with the Heidelberg
      Retina Flowmeter (HRF) to study the relationship between HRF-measured flow and
      actual flow. The initial experiments (n = 2) were conducted to establish the
      approximate velocity operating range of the HRF with single HRF measurements
      across a wide range of flow rates, whereas the subsequent experiments (n = 9)
      were concentrated within this operating range with five HRF measurements at each
      flow rate. RESULTS: When pump flow rates were converted to actual velocity at the
      measurement point for the initial experiments, the velocity operating range of
      the HRF was approximately 0.08 to 1.0 mm/s. For velocities of >1 mm/s, HRF
      measured velocity was not linearly related to actual velocity. Within the
      operating range, there was a highly significant linear relationship between HRF
      measured flow and actual flow (0.935 < or = r < or = 0.990, p < 0.001). When the
      curves of HRF-measured velocity versus actual velocity for the different
      experiments were plotted, they largely superimposed. The variability of the HRF
      measurements was between 3.57% and 4.05% and was independent of flow rate.
      CONCLUSIONS: SLDF measures reliably and linearly within a given operating range.

PMID- 9264304
TI  - The effect of interleukin-1alpha on outflow facility in rat eyes.
AB  - PURPOSE: The authors investigated whether regulation of the trabecular
      extracellular matrix turnover rate and remodeling plays an important role in
      decreasing outflow resistance by determining the effect of intracamerally given
      interleukin-1alpha, a known stimulator of the expression of trabecular matrix
      metalloproteinases, on outflow facility of albino rat eyes. MATERIALS AND
      METHODS: Forty normal albino rats (Sprague-Dawley), weighing 250 to 300 g, were
      studied. Rats were anesthetized by intraperitoneal pentobarbital sodium (30
      mg/kg) injection. The rats were separated into four groups and given 5, 10, 25,
      or 50 units of interleukin-1alpha injected intracamerally in one eye. Bovine
      serum albumin in phosphate-buffered saline, which was used to dissolve the
      interleukin-1alpha, was injected in the fellow eye as a control. Outflow facility
      was measured by two-level constant pressure perfusion 1, 3, and 7 days after
      injection. RESULTS: The eyes treated with 50 units of interleukin-1alpha showed a
      statistically significant increase of outflow facility by 37% compared with the
      contralateral control eyes 3 days after injection, but returned to normal levels
      in 7 days. The eyes treated with 5, 10, 25, or 50 units of interleukin-1alpha
      showed outflow facility increases of 12%, 20%, 39%, and 37%, respectively, 3 days
      after injection. CONCLUSION: Interleukin-1alpha increased the outflow facility,
      supporting the hypothesis that regulation of trabecular meshwork extracellular
      matrix plays a role in trabecular outflow resistance.

PMID- 9264306
TI  - The ability of Medmont M600 automated perimetry to detect threats to fixation.
AB  - PURPOSE: The authors studied the sensitivity and specificity of the Medmont M600
      central 10 degrees program (Medmont PTY Ltd., Camberwell, Victoria, Australia) in
      identifying paracentral threats to fixation mapped on the Humphrey program 10-2
      (Humphrey Inst. Inc., San Leandro, CA, U.S.A.). METHODS: Humphrey automated
      threshold perimetry (program 10-2) and Medmont M600 automated threshold perimetry
      (central 10 degrees program) were performed on 62 eyes of 62 patients with
      glaucoma, and their paracentral point defects on the field were investigated. The
      sensitivity and specificity of Medmont central 10 degrees program were analyzed.
      RESULTS: The sensitivity and specificity of Medmont M600 central 10 degrees field
      was 78% and 81% within 1 degree, and 95% and 83% within 3 degrees in detecting
      the field defects on the Humphrey program 10-2. The Medmont M600 central 10
      degrees threshold visual field test took 36% of the testing time required for the
      Humphrey threshold 10-2 visual field examination. CONCLUSION: The Medmont
      perimeter seems to be efficient in its performance of central threshold testing
      and significantly cuts down the test time.

PMID- 9264305
TI  - Brimonidine: a new alpha2-adrenoreceptor agonist for glaucoma treatment.
AB  - PURPOSE: Brimonidine is a highly selective alpha2-adrenoceptor agonist. It has
      intraocular pressure (IOP)-lowering characteristics similar to other alpha2
      agonists and acts by reducing aqueous humor production and increasing uveoscleral
      outflow. It is oxidatively stable, which may account for its lower reported rate
      of ocular allergy compared with other alpha2-agonists. The focus of this report
      is to review the receptor pharmacology and clinical experience with brimonidine
      tartrate, the newest of the alpha2-adrenergic agonists. METHODS: Clinical studies
      have been performed for acute indications using the 0.5% concentration and
      chronic indications using the 0.2% concentration. RESULTS: Brimonidine 0.5% given
      as one drop before, after, or both before and after 360 degrees argon laser
      trabeculoplasty significantly lowers the incidence of postlaser IOP spikes.
      Brimonidine 0.2% instilled twice daily offers long-term IOP control comparable
      with that achieved with timolol 0.5% and better than betatolol 0.25% suspension.
      CONCLUSIONS: In light of these data, brimonidine 0.5% may be considered for
      prophylaxis against laser-induced IOP spikes and brimonidine 0.2% for chronic use
      in patients with ocular hypertension and glaucoma.

PMID- 9264307
TI  - Neuroprotection: the next breakthrough in glaucoma? Proceedings of the Third
      Annual Optic Nerve Rescue and Restoration Think Tank.

PMID- 9264308
TI  - An alternative molecular mechanism of action of 5-fluorouracil, a potent
      anticancer drug.
AB  - It is assumed that the primary mode of action of 5-fluorouracil (5-FUra) is
      mediated via inhibition of thymidylate synthetase. Persistent inhibition of
      cellular proliferation after treatment of the 5-FUra-inhibited cells with
      exogenous thymidine do not support the notion that the anti-proliferitive action
      of 5-FUra is due exclusively to inhibition of DNA replication. Our studies have
      revealed an alternative mechanism of action at the level of pre-ribosomal RNA
      (pre-rRNA) processing. Pre-rRNA processing was inhibited completely in vitro as
      well as in S-100 extract from the mouse lymphosarcoma P1798 cells that were
      treated with 5-FUra. Under this condition, the 5-FUra-substituted pre-rRNA
      substrate was processed efficiently at the primary processing site. This study
      showed that the activity and/or the synthesis of a factor potentially involved in
      pre-rRNA processing is blocked in cells treated with the fluoropyrimidine. UV
      cross-linking study showed that a 200 kDa polypeptide designated ribosomal RNA
      binding protein (RRBP) was absent in the S-100 extract from the drug-treated
      mouse lymphosarcoma cells. Since a polypeptide that cross-links to a processing
      site on RNA is usually involved in the RNA processing, RRBP may have a direct
      role in pre-rRNA processing. A key molecular mechanism far the antiproliferative
      action of 5-FUra may be due to its interference with the activity and/or
      synthesis of RRBP. Exposure of cells to 5-FUra did not inhibit the interaction
      between U3 small nucleolar RNA (snoRNA) and pre-rRNA at the primary processing
      site (a key step in the processing reaction) and the formation of U3 small
      nucleolar ribonucleoprotein (snoRNP). Treatment of cells with the
      fluoropyrimidine did not block the 3' end processing of pre-messenger RNA (pre
      mRNA). This article also discusses the effects of 5-FUra on pre-mRNA splicing and
      mRNA translation, and proposes other avenues of research to explore further the
      mechanism of action of this important pyrimidine analog.

PMID- 9264309
TI  - Human placental cholinergic system.
AB  - The occurrence of acetylcholine (ACh)-like activity in human placenta, a tissue
      without innervation, has been known for more than 60 years. However, the non
      neuronal functions of ACh in human placenta are not clearly understood. The
      components of the cholinergic system-ACh, choline acetyltransferase,
      acetylcholinesterase, butyrylcholinesterase, muscarinic receptors, and nicotinic
      receptors--in human placenta have been demonstrated by unequivocal methods.
      Primate placentae store and release ACh by mechanisms similar to those of nervous
      tissue. However, there are many gaps in our knowledge, which include: (a)
      endogenous quaternary ammonium compounds other than ACh in human placental
      extracts; (b) the specificity of placental enzymes; (c) the subtypes and
      structures of placental muscarinic and nicotinic receptors; and (d) the
      significance of placental alpha-bungarotoxin binding proteins, ACh receptor
      stimulation-cellular signaling by second messengers, and activation of immediate
      early target genes (C-fos, C-jun) encoding transcription factors. Several
      hypothetical non-neuronal functions of ACh in placenta have been postulated based
      upon available experimental evidence. These include: (a) regulation of blood flow
      and fluid volume in placental vessels; (b) opening and closing of trophoblastic
      channels; (c) induction of contractile properties to myofibroblasts; (d)
      facilitation of amino acid transport necessary for fetal growth across placenta;
      (e) release of placental hormones; and (f) modulation of the formation of
      myometrial and placental prostaglandins in human parturition. All of these roles
      are reasonable, and some of these roles mav turn out to be linked to one another
      to influence or maintain placental function.

PMID- 9264310
TI  - Dual cytotoxic mechanisms of submicromolar taxol on human leukemia HL-60 cells.
AB  - Taxol-induced mitotic block and apoptosis were investigated using taxol-sensitive
      human leukemia HL-60 cells at submicromolar concentrations of the drug. Cells
      exposed to either 20 nM taxol for 1 hr or 10 nM taxol for 12 hr were able to
      resume normal growth, whereas cells exposed to 60 nM taxol for 1 hr or 10 nM
      taxol for 24 hr failed to proliferate after drug removal. Progressive changes in
      the percentage of mitotic block and apoptosis induced by these four treatment
      protocols were monitored continuously for 3-5 days after drug removal. Cells
      treated with 20 nM taxol for 1 hr showed a mitotic block without a subsequent
      increase in apoptosis, whereas cells treated with 10 nM taxol for 12 hr showed an
      increase in apoptotic ratio within several hours without an increase in mitotic
      block. These results indicate that apoptosis does not necessarily result from
      mitotic block and that these two phenomena can occur independently of each other.
      Drug sensitivity at progressive stages of the cell cycle was also investigated.
      The results showed that, in addition to the cells in G2/M phase, the cells in S
      phase were also sensitive to the drug, especially to a prolonged treatment. These
      results suggest that, in HL-60 cells, the apoptotic programs can be initiated in
      either the G2/M or S phase and represent two different cytotoxic mechanisms of
      taxol.

PMID- 9264311
TI  - Regulation of the function of P-glycoprotein by epidermal growth factor through
      phospholipase C.
AB  - Many multidrug-resistant (MDR) cell lines overexpress the epidermal growth factor
      receptor (EGFR) as well as P-glycoprotein (P-gp). However, the role of the
      increased EGFR in P-gp-mediated drug resistance remains unclear. Since recent
      studies suggest that activation of phospholipase C (PLC) could increase the
      phosphorylation of P-gp, and activation of the EGFR would also activate PLC, we
      investigated whether the effect of epidermal growth factor (EGF) on the
      phosphorylation of P-gp was mediated through PLC. Treatment of the human MDR
      breast cancer cell line, MCF-7/AdrR, with EGF increased the phosphorylation of P
      gp by 20-50%. The increased phosphorylation of P-gp was accompanied by
      stimulation of PLC activity, as measured by the production of inositol, 1,4,5
      trisphosphate and diacylglycerol, products of phosphatidylinositol-4,5
      bisphosphate hydrolysis. Treatment of MDR cells with EGF also had detectable
      effects on P-gp function. For example, following incubation of MCF-7/AdrR cells
      with ECF, we observed a consistent decrease in total vinblastine (VBL)
      accumulation. Kinetic analysis revealed this change to be due to an increase in
      membrane efflux. The latter was measured by the initial uptake velocity, which
      was inhibited by EGF. VBL uptake measured at 0-320 sec was inhibited by 20-40%,
      which was associated with a similar increase in VBL efflux. EGF had no effect on
      drug accumulation, uptake, or efflux in sensitive MCF-7 cells. These data
      indicate that EGF can modulate the phosphorylation and function of P-gp, and
      suggest that this effect may be initiated by the activation of PLC.

PMID- 9264312
TI  - Interactions of amphetamine analogs with human liver CYP2D6.
AB  - The interaction of fifteen amphetamine analogs with the genetically polymorphic
      enzyme CYP2D6 was examined. All fourteen phenylisopropylamines tested were
      competitive inhibitors of CYP2D6 in human liver microsomes. The presence of a
      methylenedioxy group in the 3,4-positions of both amphetamine (Ki = 26.5 microM)
      and methamphetamine (Ki = 25 microM) increased the affinity for CYP2D6 to 1.8 and
      0.6 microM, respectively. Addition of a methoxy group to amphetamine in the 2
      position also increased the affinity for CYP2D6 (Ki = 11.5 microM). The compound
      with the highest affinity for CYP2D6 was an amphetamine analog (MMDA-2) having
      both a methoxy group in the 2-position and a methylenedioxy group (Ki = 0.17
      microM). Mescaline did not interact with CYP2D6. O-Demethylation of p
      methoxyamphetamine (PMA) by CYP2D6 was characterized (Km = 59.2 +/- 22.4 microM,
      and Vmax = 29.3 +/- 16.6 nmol/mg/hr, N = 6 livers). This reaction was negligible
      in CYP2D6-deficient liver microsomes, was inhibited stereoselectively by the
      quinidine/quinine enantiomer pair, and was cosegregated with dextromethorphan O
      demethylation (r = 0.975). The inhibitory effect of methylenedioxymethamphetamine
      (MDMA) was enhanced by preincubation with microsomes, suggesting that MDMA may
      produce a metabolite complex with CYP2D6. These findings suggest that
      phenylisopropylamines as a class interact with CYP2D6 as substrates and/or
      inhibitors. Their use may cause metabolic interactions with other drugs that are
      CYP2D6 substrates, and the potential for polymorphic oxidation via CYP2D6 may be
      a source of interindividual variation in their abuse liability and toxicity.

PMID- 9264313
TI  - Possible involvement of multiple cytochrome P450S in fentanyl and sufentanil
      metabolism as opposed to alfentanil.
AB  - Fentanyl, sufentanil, and alfentanil are commonly used as opioid analgesics.
      Alfentanil clearance has previously been shown to exhibit an important
      interindividual variability, which was not observed for fentanyl or sufentanil.
      Differences in pharmacokinetic parameters of alfentanil have previously been
      associated with the wide distribution of CYP3A4, the only known hepatic
      cytochrome P450 monooxygenase (CYP) involved in the conversion of alfentanil to
      noralfentanil. Little is known about the involvement of CYP enzymes in the
      oxidative metabolism of fentanyl and sufentanil. Microsomes prepared from
      different human liver samples were compared for their abilities to metabolize
      fentanyl, sufentanil and alfentanil, and it was found that disappearance of the
      three substrates was well correlated with immunoreactive CYP3A4 contents but not
      with other CYPs, including CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2D6 and CYP2E1.
      Specific known inhibitors of CYP enzymes gave similar results, whereas the use of
      recombinant human CYP enzymes expressed in yeast provided information about the
      possible involvement of other CYPs than CYP3A4 in the biotransformation of
      fentanyl and sufentanil. The possible in vivo interaction of fentanyl and
      sufentanil with other drugs catalyzed by CYP3A4 is also discussed.

PMID- 9264314
TI  - Activation by beta-carbolines of G-proteins in HL-60 membranes and the bovine
      retinal G-protein transducin in a receptor-independent manner.
AB  - Naturally occurring beta-carbolines are lipophilic compounds which show
      psychotropic and physiological effects in mammals. They bind to distinct high
      affinity binding sites in various mammalian tissues. However, the mechanism by
      which the beta-carbolines affect transmembrane signal transduction processes is
      still unknown. Since beta-carbolines are cationic-amphiphilic substances and
      since such substances are known to activate heterotrimeric regulatory guanine
      nucleotide binding proteins (G-proteins) in a receptor-independent manner, we put
      forward the hypothesis that beta-carbolines act directly on G-proteins.
      Therefore, we investigated the ability of beta-carbolines to stimulate high
      affinity GTP hydrolysis in membranes of dibutyryl-cAMP differentiated HL-60 cells
      and of the purified bovine G-protein, transducin (TD). The beta-carbolines
      norharman and harman, stimulated the GTPase in HL-60 membranes with an EC50 of
      410 microM and 450 microM, respectively, and a maximum effect at 1 mM each.
      Norharman and harman stimulated the GTPase of TD with an EC50 of 60 microM and
      300 microM, and a maximum at 1 mM for both compounds. The stimulatory effect of
      norharman in HL-60 membranes was pertussis toxin-sensitive. Structure/activity
      characteristics of the beta-carbolines showed a specificity of norharman to
      stimulate the GTPase of TD, because norharman activated GTP hydrolysis in HL-60
      membranes approximately 7 times less potently than that of TD. Norharman was a
      five-fold more potent activator of TD than tetrahydronorharman. Hydroxylation of
      the beta-carboline molecule in position 6 led to a loss of GTPase-activating
      properties. Our data suggest that naturally occurring beta-carbolines are a novel
      class of receptor-independent G-protein activating substances. This mechanism
      could contribute to their diverse biological effects.

PMID- 9264315
TI  - Pharmacological influence of antirheumatic drugs on proteoglycans from
      interleukin-1 treated articular cartilage.
AB  - The purpose of this study was to examine whether drugs used in the treatment of
      arthritic disorders possess any inhibitory potential on the proteoglycanolytic
      activities of matrix metalloproteinases (MMPs), and to determine whether drugs
      which inhibit these enzymes also modulate the biosynthesis and release of
      proteoglycans (PGs) from interleukin-1-(IL-1) treated articular cartilage
      explants. The cartilage-bone marrow extract and the glycosaminoglycan-peptide
      complex (DAK-16) dose-dependently inhibited MMP proteoglycanases in vitro when
      tested at concentrations ranging from 0.5 to 55 mg/mL, displaying an IC50 value
      of 31.78 mg/mL and 10.64 mg/mL (1.9 x 10[-4] M) respectively. (R,S)-N-[2-[2
      (hydroxyamino)-2-oxoethyl]-4-methyl-1-oxopentyl++  +]-L-leucyl-L
      phenylalaninamide (U-24522) proved to be a potent inhibitor of MMP
      proteoglycanases (IC50 value 1.8 x 10[-9] M). None of the other tested drugs,
      such as possible chondroprotective drugs, nonsteroidal anti-inflammatory drugs
      (NSAIDs), disease modifying antirheumatic drugs (DMARDs), glucocorticoids and
      angiotensin-converting enzyme inhibitors tested at a concentration of 10(-4) M
      displayed any significant inhibition. Only U-24522, tested at a concentration
      ranging from 10(-4) to 10(-6) M, significantly inhibited the IL-1-induced
      augmentation of PG loss from cartilage explants into the nutrient media, whereas
      DAK-16 and the cartilage-bone marrow extract were ineffective. DAK-16 and the
      cartilage-bone marrow extract did not modulate the IL-1-mediated reduced
      biosynthesis and aggregability of PGs by the cartilage explants. The addition of
      10(-5) M U-24522, however, partially maintained the aggregability of PGs ex vivo.
      In our experiments, both possible chondroprotective drugs as well as U-24522
      demonstrated no cytotoxic effects on chondrocytes.

PMID- 9264317
TI  - Relationship between flavonoid structure and inhibition of phosphatidylinositol 3
      kinase: a comparison with tyrosine kinase and protein kinase C inhibition.
AB  - Depending on their structure, flavonoids display more or less potent inhibitory
      effects on the growth and proliferation of certain malignant cells in vitro, and
      these effects are thought to be due to inhibition of various enzymes. We
      investigated the inhibitory action of fourteen flavonoids of different chemical
      classes on phosphatidylinositol 3-kinase alpha (PI 3-kinase alpha) activity, an
      enzyme recently shown to play an important role in signal transduction and cell
      transformation. Of the fourteen flavonoids tested, myricetin was the most potent
      PI 3-kinase inhibitor (IC50 = 1.8 microM), while luteolin and apigenin were also
      effective inhibitors, with IC50 values of 8 and 12 microM, respectively. Fisetin
      and quercetin, as previously reported, were also found to significantly inhibit
      PI 3-kinase activity. The same flavonoids were also analyzed for inhibition of
      epidermal growth factor receptor (EGF-R), intrinsic tyrosine kinase and bovine
      brain protein kinase C (PKC). At elevated doses, some of these flavonoids were
      found to also cause significant inhibition of PKC and tyrosine kinase activity of
      EGF-R. A structure-activity study indicated that the position, number and
      substitution of the hydroxyl group of the B ring, and saturation of the C2-C3
      bond are important factors affecting flavonoid inhibition of PI 3-kinase. They
      may also play a significant role in specificity of inhibition and could help to
      provide a basis for the further design of specific inhibitors of this lipid
      kinase. Finally, possible relationships between the antitumoral properties of
      these flavonoids and their biological activities are discussed.

PMID- 9264316
TI  - Differential effect of hypophysectomy and growth hormone treatment on hepatic
      glucuronosyltransferases in male rats: evidence for an action at a
      pretranslational level for isoforms glucuronidating bilirubin.
AB  - The influence of growth hormone (GH) on 4-nitrophenol, bilirubin, testosterone,
      androsterone and estrone glucuronidation activities was studied in fully
      activated male rat hepatic microsomes. Sham-operated and hypophysectomized
      animals were injected with two different dosages of GH, mimicking either the male
      or female GH secretion pattern. Half the animals received thyroxine and cortisol
      in concentrations chosen to compensate for the lack of thyroid hormones and
      glucocorticoids in hypophysectomized rats. GH induced a decrease in several
      glucuronidation activities: bilirubin glucuronidation in both sham-operated and
      cortisol/ thyroxine-treated hypophysectomized rats in a dose-dependent manner,
      testosterone glucuronidation in hypophysectomized animals, and androsterone and
      estrone glucuronidation in cortisol/thyroxin-treated hypophysectomized rats. 4
      nitrophenol glucuronidation was not affected by GH treatment. A hypothetical
      "feminizing" effect of GH (due to an almost continuous secretion) could not be
      invoked to explain these results, contrary to what has been observed elsewhere
      for other hepatic enzyme activities. Hypophysectomy altered all the activities
      tested, with bilirubin the most modified (a 200% enhancement). Restoration of
      control values was achieved in hypophysectomized animals with cortisol/thyroxine
      replacement together with a low dosage of GH (mimicking a male GH secretion
      pattern), except for androsterone glucuronidation activity where both GH and
      cortisol/thyroxine treatments reinforced the decreasing effect of hypophysectomy.
      Variations in protein amounts were correlated to variations in bilirubin,
      testosterone and androsterone conjugation activities induced by hypophysectomy
      and GH treatment. Reverse transcription-polymerase chain reaction (RT-PCR) mRNA
      analysis of bilirubin cluster isoforms or uridine diphosphate
      glucuronosyltransferase 1B1 (UGT1B1), UGT1B2 and UGT1B5 showed that GH controlled
      the different isoforms involved in bilirubin glucuronidation differentially at a
      pretranslational level.

PMID- 9264318
TI  - Iron mobilization from crocidolite as enhancer of collagen content in rat lung
      fibroblasts.
AB  - Asbestos exposure causes pulmonary fibrosis by mechanisms that remain uncertain.
      There is increasing evidence that iron from asbestos is responsible for many of
      its effects. In this paper, we investigated the effect of iron mobilized from
      crocidolite asbestos on collagen content in rat lung fibroblast cultures under
      serum-free conditions. Crocidolite (2, 4, 6 microg/cm2 well) increased collagen
      content in a dose-dependent manner (+42 +/- 8, +92 +/- 10, and +129 +/- 13% vs
      controls). This effect was specific for collagen, since it did not alter total
      protein content and was inhibited by the iron chelator deferoxamine (DFO).
      Preincubation of crocidolite with citrate (1 mM) for 48 hr resulted in iron
      mobilization (51 microM) and increased collagen production (>3-fold) in treated
      cells. These effects occurred without the intervention of serum factors. The
      absence of cell damage, proliferation or lipid peroxidation leads to the
      supposition that iron from crocidolite per se may act as a profibrogenic agent.
      Although the in vivo participation of other cells and factors cannot be excluded,
      we conclude that iron released from crocidolite plays a role in collagen increase
      occurring during asbestosis.

PMID- 9264319
TI  - Effect of 2-(1-piperazinyl)-4H-pyrido[1,2-a]pyrimidin-4-one (AP155) on human
      platelets in vitro.
AB  - The effect on human platelets of 2-(1-piperazinyl)-4H-pyrido[1,2-a]pyrimi din-4
      one (AP155) was tested in vitro by measuring cyclic adenosine monophosphate
      (cAMP) level, cytosolic Ca++, [(125I)]fibrinogen binding as well as aggregation
      induced by several agonists. AP155 dose-dependently inhibited aggregation both in
      platelet rich plasma (PRP) and in washed platelets (WP), exerting its maximal
      power in the presence of collagen, ADP and platelet activating factor (PAF). It
      specifically inhibited the activity of cAMP high affinity phosphodiesterase
      (PDE), resulting in a sufficient increase in cAMP levels to activate cAMP
      dependent protein kinase. AP155 was able to inhibit aggregation, the increase in
      cytosolic Ca++ induced by thrombin, and fibrinogen binding to ADP or thrombin
      stimulated platelets. Thus, this new pyridopyrimidine derivative exerts its
      antiplatelet activity by increasing cAMP intracellular concentration.

PMID- 9264320
TI  - Serine protease inhibition and mitochondrial dysfunction associated with
      cisplatin resistance in human tumor cell lines: targets for therapy.
AB  - Indicators of mitochondrial function were studied in two different cell culture
      models of cis-diamminedichloroplatinum-II (CDDP) resistance: the intrinsically
      resistant human ovarian cancer cell line CI-80-13S, and resistant clones (HeLa
      S1a and HeLa-S1b) generated by stable expression of the serine protease inhibitor
      plasminogen activator inhibitor type-2 (PAI-2), in the human cervical cancer cell
      line HeLa. In both models, CDDP resistance was associated with sensitivity to
      killing by adriamycin, etoposide, auranofin, bis[1,2
      bis(diphenylphosphino)ethane]gold(I) chloride ([Au(DPPE)2]Cl), CdCl2 and the
      mitochondrial inhibitors rhodamine-123 (Rh123), dequalinium chloride (DeCH),
      tetraphenylphosphonium (TPP), and ethidium bromide (EtBr) and with lower
      constitutive levels of ATP. Unlike the HeLa clones, CI-80-13S cells were
      additionally sensitive to chloramphenicol, 1-methyl-4-phenylpyridinium ion
      (MPP+), rotenone, thenoyltrifluoroacetone (TTFA), and antimycin A, and showed
      poor reduction of 1-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide
      (MTT), suggesting a deficiency in NADH dehydrogenase and/or succinate
      dehydrogenase activities. Total platinum uptake and DNA-bound platinum were
      slightly lower in CI-80-13S than in sensitive cells. The HeLa-S1a and HeLa-S1b
      clones, on the other hand, showed poor reduction of triphenyltetrazolium chloride
      (TTC), indicative of low cytochrome c oxidase activity. Total platinum uptake by
      HeLa-Sla was similar to HeLa, but DNA-bound platinum was much lower than for the
      parent cell line. The mitochondria of CI-80-13S and HeLa-S1a showed altered
      morphology and were fewer in number than those of JAM and HeLa. In both models,
      CDDP resistance was associated with less platinum accumulation and with
      mitochondrial and membrane defects, brought about one case with expression of a
      protease inhibitor which is implicated in tumor progression. Such markers may
      identify tumors suitable for treatment with gold phosphine complexes or other
      mitochondrial inhibitors.

PMID- 9264321
TI  - Receptor-mediated diacylglycerol kinase translocation dependent on both transient
      increase in the intracellular calcium concentration and modification by protein
      kinase C.
AB  - Diacylglycerol kinase (DG kinase) is activated by various stimuli in many types
      of cells. We reported earlier that carbachol (CCh) induced DG kinase
      translocation from the cytosolic fraction to the membrane fraction in guinea pig
      taenia coli (Biochem. Pharmacol., 50: 591-599, 1995). In this study, the
      regulation mechanisms of DG kinase translocation are reported, based on the
      following findings: 1) CCh sustained an increase in DG kinase in the membrane
      fraction and a decrease in the cytosolic fraction; 2) blocking calcium influx by
      removing extracellular calcium did not affect the CCh-induced sustained DG kinase
      translocation; 3) exposing purified protein kinase C (PKC) to DG kinase increased
      DG kinase affinity to octylglycoside micelles only with the enzyme extracted from
      the cytosolic fraction; and 4) CCh-induced DG kinase translocation was reversed
      by removing CCh, and the serine/threonine phosphatase inhibitor, okadaic acid,
      blocked the reversal of the translocation. These results suggest that CCh-induced
      DG kinase translocation is promoted by both a transient increase in intracellular
      calcium, which may be released from the intracellular store, and by DG kinase
      phosphorylation by PKC.

PMID- 9264322
TI  - Selective mechanism-based inactivation of peptidylglycine alpha-hydroxylating
      monooxygenase in serum and heart atrium vs. brain.
AB  - Peptidylglycine alpha-hydroxylating monooxygenase (PHM; EC 1.14.17.3) catalyses
      the rate-limiting step in the post-translational activation of substance P, among
      other neuropeptides, from its glycine-extended precursor. Comparative kinetic
      studies were performed, using trans-styrylacetic acid or trans-styrylthioacetic
      acid as known mechanism-based inhibitors, of PHM isolated from rat, horse or
      human blood serum. Distinctive species differences with respect to PHM
      inactivation were observed: the efficiency of inactivation decreased in the order
      of horse >> rat > human. Trans-styrylacetic acid was more active than its
      thioether derivative. Moreover, we studied the differential sensitivity towards
      mechanism-based inactivation, of soluble PHM from rat blood serum and rat brain
      by trans-styrylacetic acid or benzylhydrazine, as well as the membrane-associated
      enzymes from rat brain and heart atrium. For the heart atrium membrane PHM or the
      soluble PHM from blood serum, inactivation rate constants k(inact)/K(I) of
      approximately 100 M(-1)sec(-1) were found with trans-styrylacetic acid. However,
      neither of the two tested compounds, at 100 microM or 12 mM, respectively, could
      inactivate the soluble or membranous PHMs from rat brain during a 15-min pre
      incubation period. Instead, under conditions of reversible inhibition, trans
      styrylacetic acid competitively inhibited the soluble or membrane-associated
      brain PHM with inhibition constants K(I) = 0.6 microM and 1.0 microM,
      respectively. Organ-selective, time-dependent inactivation of PHM with compounds
      of the above types might be an important pharmacological tool to control
      peripheral neuropeptide activation.

PMID- 9264323
TI  - Dual modulation of 5-fluorouracil cytotoxicity using folinic acid with a
      dihydropyrimidine dehydrogenase inhibitor.
AB  - Dihydropyrimidine dehydrogenase (DPD) is the key enzyme of the fluorouracil (FU)
      catabolic pathway. We have shown that tumor cells expressing a high DPD activity
      are resistant to FU (Eur J Cancer 30: 1517, 1994), and that 5-ethynyluracil
      (776C), a very potent DPD inactivator, markedly enhances the FU cytotoxic effect
      (Clin Cancer Res 1: 991, 1995). Both experimental background and clinical
      experience have demonstrated the role of folinic acid (FA) in increasing FU
      efficacy. The aim of the present study was to investigate the dual FU
      pharmacomodulation based on the combination of FU with 776C and/or FA on 7 human
      cancer cell lines (2 head and neck, 3 breast, 1 colon, 1 duodenum) expressing a
      spontaneous FU sensitivity. These cell lines were chosen according to their
      ability to respond to FU modulation by FA and/or 776C. The potency of FU
      modulation was evaluated by the ratio between FU IC50 and FU IC50 in the presence
      of the tested biomodulator(s), defined as factor F. In cell lines sensitive to FU
      modulation by 776C only (median F value with 1 microM of 776C = 2.5), the
      addition of FA did not enhance FU-776C cytotoxicity. In contrast, for cell lines
      resistant to FU modulation by 776C, the FU-FA-776C combination led to a
      significant cytotoxicity enhancement as compared to FU-FA (median F values were
      3.6 and 2.6 respectively). In cell lines responsive to FU modulation by FA and
      776C, the median F values were 2.3 and 1.8 with FA and 776C, respectively.
      Interestingly, the dual modulation by FA + 776C led to a median F value at 6.3,
      suggesting more than the additive effects of FA and 776C. This synergistic
      interaction was statistically confirmed by multivariate ANOVA (FA x 776C
      interaction). The present study points out that FA plus 776C could prove to be a
      very attractive combination for future strategies in FU biomodulation.

PMID- 9264324
TI  - 1-desamino-8-D-arginine vasopressin (DDAVP) as an agonist on V1b vasopressin
      receptor.
AB  - 1-desamino-8-D-arginine vasopressin (DDAVP) is considered a standard vasopressin
      V2 receptor-selective agonist with a potent antidiuretic effect through V2
      receptor without the induction of vasoconstriction through V1a receptor.
      Furthermore, DDAVP was reported to act as an agonist on non-V1a, non-V2 receptor
      to cause the accumulation of intracellular Ca2+ in several tissues. However, the
      agonistic activity of DDAVP against the other vasopressin receptor, V1b (or V3),
      which can accumulate intracellular Ca2+ and which we recently cloned, has not
      been clarified. Hence, we compared the characteristics of DDAVP on V1b receptor
      with those on the other vasopressin receptors. In binding experiments, DDAVP more
      strongly inhibited [3H]arginine vasopressin binding to V1b than to V2 receptor
      (Ki: 5.84 nM vs 65.9 nM). In addition, DDAVP dose-dependently stimulated inositol
      turnover in human V1b receptor-expressing COS-1 cells. DDAVP acted as a full
      agonist on human V1b receptor (EC50: 11.4 nM) as well as on human V2 receptor
      (EC50: 23.9 nM). However, DDAVP behaved as a partial agonist toward rat V1b
      receptor (intrinsic activity: 0.7, EC50: 43.5 nM), while there was no significant
      difference in the agonistic properties of arginine vasopressin on human and rat
      V1b receptor. In conclusion, DDAVP acts as an agonist on V1b receptor, as it does
      on V2 receptor. These findings will allow us to better understand the
      physiological role of V1b receptor in pancreatic beta cells and in the renal
      inner medullary collecting duct, and help us to identify as yet unknown
      vasopressin receptors through which DDAVP cause the accumulation of intracellular
      Ca2+ in other tissues.

PMID- 9264325
TI  - Tumor selectivity and transcriptional activation by azelaic bishydroxamic acid in
      human melanocytic cells.
AB  - Azelaic bishydroxamic acid (ABHA), a potent differentiating agent for lymphoid
      cells, was selectively toxic for 5 human tumor cell lines and transformed human
      melanocytes and keratinocytes (dose for 37% survival, D37, 30-100 microg/mL)
      compared with normal cells (melanocytes, fibroblasts; D37 > 300 microg/mL).
      Dendritic morphology was the only indicator found for increased differentiation,
      markers for the pigmentation pathway being unchanged or inhibited by ABHA. In
      contrast to hexamethylene bisacetamide and azelaic acid, ABHA significantly
      increased the HIV LTR, SV40 and c-fos promoter activities during a 24 hr
      treatment. Metallothionein promoter activity was enhanced by 5 hr treatment with
      ABHA in a sensitive melanoma cell line (MM96L) but was inhibited in a more
      resistant line (HeLa); c-fos promoter activity was inhibited in HeLa during this
      time. Transcription from a p53 binding response element was inhibited in MM96L by
      a 24 hr ABHA treatment but enhanced in HeLa. ABHA may represent a structural
      prototype for designing more potent and selective anti-melanoma agents.

PMID- 9264326
TI  - Differential regulation of phospholipase A2 in human leukemia cells by the
      etherphospholipid analogue hexadecylphosphocholine.
AB  - Hexadecylphosphocholine (HePC) is the main representative of a new group of
      antineoplastic agents, the alkylphosphocholines, which were originally derived
      from cytotoxic etherlysophospholipids. HePC shows antiproliferative action
      against a whole variety of tumor cells and tumors in vitro and in vivo.
      Furthermore, it also induces differentiation in some hematologic cell lines and
      prevents invasive growth of neoplastic cells in vitro. To date, the precise
      molecular mechanisms mediating the biological effects of HePC have not been
      identified yet. As etherlysophospholipids seem to inhibit some pathways of lipid
      dependent intracellular signalling, similar effects may be relevant for HePC. We
      therefore investigated the influence of HePC on phospholipase A2 (PLA2-EC 3.1.1)
      in the human leukemia cell line U 937. HePC seems to inhibit enzyme activity
      independently of protein kinase C (PKC) in differentiated U 937 cells stimulated
      by tumor necrosis factor alpha (TNFalpha). Inhibition of purified secretory PLA2
      from snake venom (EC 3.1.1.4) in vitro shows characteristics of a non-competitive
      mode. In contrast, HePC leads to an enhancement of PLA2 activity in immature
      cells which cannot be explained by changes in membrane composition. Our data
      suggest that PLA, inhibition is most probably not the mechanism by which HePC
      mediates its antiproliferative effects.

PMID- 9264327
TI  - Role of P-glycoprotein in colchicine and vinblastine cellular kinetics in an
      immortalized rat brain microvessel endothelial cell line.
AB  - Uptake and efflux of colchicine and vinblastine, whose effects are related to
      their high-affinity binding to tubulin, were studied in the immortalized rat
      brain microvessel endothelial cell line RBE4. At 10 nM extracellular drug
      concentration, uptake equilibrium was approached at 45 hr for colchicine, but at
      only 3.5 hr for vinblastine. After 1 hr preincubation with 200 nM colchicine or
      vinblastine, drug efflux fitted biexponential kinetics with an initial fast phase
      (half-life = 2.2 min and 9.6 min, respectively) and a later slow phase (half-life
      = 3.6 hr and 1.8 hr, respectively). After 6 hr preincubation with 200 nM
      colchicine, only the slow phase (half-life = 3.6 hr) could be observed. The
      colchicine and vinblastine uptake rate was increased by cyclosporin A, an
      inhibitor of the drug efflux pump P-glycoprotein, which is expressed at the blood
      brain barrier. Whereas cyclosporin A decreased vinblastine efflux, its effect on
      colchicine efflux was apparent after only 13 hr washout and was associated with
      the re-uptake by cells of colchicine molecules. Differences in uptake kinetics of
      colchicine and vinblastine could be related to differences in their lipid
      solubility, and mainly in their binding affinities to tubulin. Differences in
      efflux kinetics could in addition be explained by the involvement of P
      glycoprotein in the efflux of vinblastine, whereas efflux of colchicine was not
      influenced by this pump. Indeed, binding of colchicine to tubulin would imply
      that most intracellular colchicine may be inaccessible to P-glycoprotein. In the
      case of a cytotoxic drug such as colchicine, which is tightly bound to
      intracellular receptors, the role of P-glycoprotein within the blood-brain
      barrier would be more to protect the brain against entry of this drug than to
      detoxify the brain by its extraction.

PMID- 9264328
TI  - Release of free, redox-active iron in the liver and DNA oxidative damage
      following phenylhydrazine intoxication.
AB  - Following the subchronic intoxication of rats with phenylhydrazine, resulting in
      marked anemia, reticulocytosis, methemoglobinemia and increased hemocatheresis,
      the hepatic content of total iron was increased, as was hepatic ferritin and its
      saturation by iron. A striking increase (approximately 7-fold) was also observed
      in free iron which appeared to be redox-active. The increase in liver free iron
      involved the hepatocellular component of the liver. Since DNA is one of the
      cellular targets of redox active iron, liver DNA from phenylhydrazine-treated
      rats was analyzed by electrophoresis and found to be markedly fragmented.
      Experiments with isolated hepatocytes in culture or in suspension challenged with
      phenylhydrazine or Fe-nitrilotriacetate strongly suggested that the DNA damage
      was due to reactive iron rather than to the hepatic metabolism of
      phenylhydrazine. The levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), a
      specific marker of oxidative DNA damage, were significantly higher in
      phenylhydrazine-treated rats as compared to untreated controls. The prolongation
      of phenylhydrazine treatment over a period of 6 weeks resulted in a persistent
      damage to DNA and in phenotypic changes such as an increase in hepatocyte gamma
      glutamyl transpeptidase (gamma-GT, EC 2.3.2.2) activity. Possible relationships
      between iron overload, iron release, DNA damage and tumor initiation are
      discussed.

PMID- 9264329
TI  - Beditine, a new benzodioxane derivative, as a suppressor of human
      polymorphonuclear leukocyte and platelet activation.
AB  - Beditine, 2-(2-amino-4-thiazolyl)-1,4-benzodioxane hydrochloride is a new
      substance which reduced platelet activation and degranulation, prevented
      aggregation and superoxide generation by activated human polymorphonuclear
      leukocytes (PMNL) and inhibited the activation of arachidonate 5-lipoxygenase.
      Beditine may, therefore, be a useful agent in the treatment of cardiovascular
      disease.

PMID- 9264330
TI  - The modulation effect of vitamin E on prostaglandin E2 level and ornithine
      decarboxylase activity at the promotion phase of lung tumorigenesis in mice.
AB  - The present study was undertaken to investigate a mechanism of the inhibitory
      effect of vitamin E in urethane-induced lung tumorigenesis in mice. We assayed
      ornithine decarboxylase (ODC) activity and the prostaglandin E2 (PGE2) level in
      lung at 8 weeks after urethane injection (promotion phase). Excessive vitamin E
      feeding or indomethacin treatment suppressed the urethane-induced increase in ODC
      activity, while exogenous PGE2 overcame the effect of vitamin E on ODC activity.
      Furthermore, the amount of PGE, and the level of ODC activity were well
      correlated. These results indicate that the vitamin E-induced decrease in PGE2
      level probably contributes to the inhibition of ODC induction and the prevention
      of tumor development in the lung.

PMID- 9264332
TI  - Introduction to the thymus.

PMID- 9264331
TI  - Effects of S-adenosyl-L-methionine on platelet thromboxane and vascular
      prostacyclin.
AB  - We therefore designed the present study to evaluate the effect of S-adenosyl-L
      methionine (SAMe) on the synthesis of platelet thromboxane and vascular
      prostacyclin. The experimental materials were human blood and aortic rings from
      untreated Wistar rats; and platelets and aortic rings from Wistar rats treated
      for 7 days with SAMe at 5 or 10 mg/kg/day s.c. The administration of 10 mg/Kg/day
      of SAMe to rats significantly increased vascular production of 6-keto-PGF1alpha.
      In vitro vascular production of 6-keto-PGF1alpha increased in a concentration
      dependent manner when SAMe was incubated in the range of 10(-7) to 10(-4) M. The
      greatest increase was 167 +/- 15%, obtained in samples incubated with 5 x 10(-5)
      M SAMe. In aortic rings, lipid peroxidase production was inhibited in a
      concentration-dependent manner in the SAMe range of 10(-7) to 10(-5) M. Maximum
      inhibition (75.3 +/- 6.2%) was obtained with SAMe at 1.5 x 10(-5) M. Vascular 6
      keto-PGF1alpha production showed a significant inverse linear correlation with
      vascular lipid peroxide production (Y = -0.04x + 18.1, r = 0.7309, P < 0.0001).

PMID- 9264333
TI  - Development of the thymus.
AB  - Proper development of the thymus is critical for an individual to acquire full
      immune capability. A full complement of the components that participate in thymic
      development, interacting with each other at the correct time, is required for
      maturation. In order to establish the microenvironment necessary for T-cell
      differentiation, the epithelial primordium of the thymus must expand from
      pharyngeal endoderm with the aid of contributions from the ectoderm. Experimental
      studies have established the importance of mesenchymal derivatives from the
      neural crest in functional development of the epithelial primordium. Interfering
      with this process inhibits thymic development in a manner similar to that
      observed in congenital conditions such as the DiGeorge syndrome and the fetal
      alcohol syndrome. These observations provide clues to understanding the origin of
      defects in thymus-dependent immunity, and point the way to studies that will
      expand our understanding of the controls that are involved in genetic and
      environmental factors impacting on this process.

PMID- 9264334
TI  - Thymic microenvironment at the light microscopic level.
AB  - The thymus is a primary lymphoid organ that serves the immune system by providing
      an optimal microenvironment for developing T cells to rearrange the genes
      encoding the T-cell receptor and to undergo positive and negative selection in
      shaping the peripheral T-cell repertoire. The microenvironment of the organ is
      peculiar among lymphoid organs, as the supporting stroma consists of reticular
      epithelial cells. Bone marrow-derived interdigitating cells and macrophages are
      the main accessory cell populations. The epithelium, interdigitating cells, and
      macrophages each contribute to the T-cell selection process. During the last
      decade knowledge has been gathered that these cell populations show a
      considerable heterogeneity, as documented for subcellular features and
      immunologic phenotype. This heterogeneity may reflect various stages in
      differentiation, but may otherwise be linked to the functional activity of the
      cells. The authors survey the major cell populations, i.e., epithelial cells and
      lymphocytes. Macrophages and interdigitating cells are briefly discussed.
      Emphasis is given to functional aspects of histologic/ cytologic features.

PMID- 9264335
TI  - Heterogeneity of epithelial cells in the rat thymus.
AB  - The morphological heterogeneity of the thymic epithelium has been well documented
      both at the light and electron microscopic level. Immunohistochemistry has
      revealed four broad classes of epithelial cells (EC): subcapsule/perivascular,
      cortical, medullary EC, and medullary Hassall's corpuscles. Ultrastructural
      analysis has revealed further heterogeneity. In the cortex, four EC subtypes have
      been described ultrastructurally: subcapsular/perivascular, "pale,"
      "intermediate," and "dark" EC. These subtypes are also present in the medulla.
      Two additional EC subtypes are restricted to the medulla: an undifferentiated
      subtype, and a subtype displaying signs of high metabolic activity. Based on the
      morphological features of the epithelium, it has been hypothetized that the
      thymic EC subtypes represent a process of differentiation.

PMID- 9264337
TI  - Thymic nurse cells: their functional ultrastructure.
AB  - Thymic nurse cells are defined in vitro as multicellular complexes of epithelial
      cells and thymocytes. Although these structures have been implicated in the
      intrathymic differentiation of thymocytes, little is known about the biology of
      this cell complex and about the occurrence of the cells in the thymus in situ.
      Therefore, to clarify the matter, in this review we have presented
      characteristics of epithelial cells capable of forming complexes with thymocytes,
      in light of the literature data and the experience of the authors. The structure
      of cells within the complexes allowed us to distinguish three types of thymic
      nurse cells. Three-dimensional reconstruction of the thymus and observations
      employing TEM and SEM demonstrated the presence of distinct types of complexes in
      various topographic regions of the thymus. Where possible, the functional
      relevance of the morphological data was analyzed.

PMID- 9264336
TI  - Immuno-electron microscopy of the thymic epithelial microenvironment.
AB  - Normal T cell development depends upon interactions between progenitor cells and
      the thymic microenvironment. Monoclonal antibodies (Mabs) have been used to
      define subtypes of thymic epithelium by light microscopy (clusters of thymic
      epithelial staining [CTES]). We have now used a range of these Mabs together with
      gold-coupled reagents in immuno-electron microscopy to study the fine cellular
      distribution of the molecules to which the antibodies bind. Anti-cytokeratin
      antibodies were used to identify all thymic epithelial cells, while the
      distribution of MHC class II molecules was revealed with Mabs to shared
      nonpolymorphic determinants. MR6, a CTES III Mab, shows strong surface labelling
      of cortical epithelial cells and thymic nurse cells and very weak surface
      staining of thymocytes, medullary macrophages, and interdigitating cells. Mab
      8.18 (CTES V) also labels a cell surface molecule; this is present on Hassall's
      corpuscles and associated medullary epithelial cells. The molecules detected by
      Mabs MR6 and 8.18 are therefore located in a position where they are available to
      interact with external cellular and soluble signals within the thymus. In
      contrast, Mabs MR10 and MR19 (CTES II) recognise intracellular molecules within
      subcapsular, perivascular, and medullary epithelium. A similar distribution was
      seen with Mab 4beta, directed against the thymic hormone thymulin, although, in
      addition to the expected intracellular epithelial staining, large lymphoblasts in
      the subcapsular zone showed surface positivity, indicating the presence of
      thymulin bound to surface receptors on these early lymphoid cells. As expected,
      MHC class II molecules were expressed on some medullary and essentially all
      cortical epithelial cells. However, although most subcapsular epithelium was
      class II-negative, some cells did express these MHC molecules on their apical
      surface and on the surface of their cytoplasmic extensions into the cortex.
      Interestingly, some cortical epithelial cells surrounding capillaries were
      positive for both MR6 (CTES III) and for MR10, MR19, and 4beta (CTES II). Double
      labelling experiments, using MR6 and MR19 simultaneously, revealed a double
      positive perivascular epithelial cell population in the thymic cortex. The
      possibility that these cells represent a thymic epithelial progenitor population
      is discussed.

PMID- 9264338
TI  - Human thymic dendritic cells.
AB  - ABSTRACT Human thymic dendritic cells (DC) represent a member of the bone marrow
      derived dendritic cell family. They have a dendritic shape and are found in small
      numbers mainly at the corticomedullary border and in medullary regions of the
      thymus. Human thymic DC were isolated by density gradient separation, followed by
      treatment with CD2, CD7, CD1, and CD11b mAb and immunobeads magnetic separation.
      The resulting population contains 60-75% brightly HLA-DR+ cells which present the
      morphological characteristics of DC observed in situ. Extensive phenotypic
      analysis confirmed that they are of mesenchymal origin and that some express
      CD11a and CD54 molecules. Freshly isolated DC do not stain with a wide variety of
      anti-T-B and -monocyte or -macrophage mAb. However, they acquire the CD1 molecule
      after a few days in culture. By using a cell sorter we obtained 90-95% of
      purified human thymic DC. Functional studies have shown that human thymic DC are
      potent activators in mixed lymphocyte reactions, act as accessory cells in
      mitogenic thymocyte proliferation, increase the thymocyte proliferative response
      to a toxin signal, and produce IL-1. They also formed spontaneous physical
      associations with thymocytes, which raises questions about the implication of DC
      in differentiation and/or maturation processes of thymocytes.

PMID- 9264339
TI  - Thymic epithelial cell culture.
AB  - Culture of epithelial cells from the thymus of children and laboratory animals
      has been used for more than two decades to evaluate both the nature of these
      cells and their importance in the selection and maturation of functional T cells.
      Especially by the use of serum-free cultures and by establishment of cell lines
      from cultured thymic epithelial cells (TEC), it has been possible to obtain basic
      information on morphology of subpopulations of TEC, including surface
      determinants of importance for interactions with T-cell precursors, and on the
      repertoire of cytokines secreted by different types of TEC. The available
      information, obtained by co-culture of pre-T cells and TEC, on the effects of TEC
      on the fate of pre-T cells suggests that cultured TEC/TEC lines are able both to
      secrete needed cytokines for T-cell development, and to deliver signals needed
      for T-cell selection. In vivo results showing cross-talk between TEC and T cells
      indicate that more careful evaluation of interactions between well-defined
      subtypes of cultured TEC and co-cultured subpopulations of pre-T cells (as well
      as macrophages/dendritic cells) will be of importance in evaluation of the
      function of the thymus.

PMID- 9264340
TI  - Thymic microvascular system.
AB  - Morphological studies of the microcirculatory system in the thymus were reviewed
      in regards to methodology and structural organization of blood and lymphatic
      vessels. The blood capillaries and postcapillary venules (PCVs) in the thymus are
      characterized by a double-walled structure. These vessels are surrounded more or
      less by perivascular spaces (PVSs) containing many lymphocytes. This space is
      delimited on the one side by abluminal surface of the vascular endothelium and on
      the other side by cytoplasmic processes of epithelial reticular cells. There are
      interruptions or gaps on the outer epithelial reticular layer. The lymphatic
      vessels can be distinguished histochemically from blood vessels based on strong
      5'-nucleotidase (5'-Nase) activity. The 5'-Nase-positive lymphatic vessels were
      seen predominantly in the capsule and interlobular connective tissue but
      sometimes in the immediate vicinity of the PVS around the PCV, when a discrete
      opening in the lymphatic wall next to the PVS was found. Thus, it may be regarded
      as an initial part of lymphatics closely associated with the PVS, suggesting a
      possible route for lymphocyte efflux into the lymphatic vessel from the PVS. The
      endothelial cells of lymphatic vessels as well as PCVs are often infiltrated by
      lymphocytes, particularly more heavily during acute involution of the thymus.
      These images represent the migration of lymphocytes into the blood or lymphatic
      microcirculation.

PMID- 9264341
TI  - Functional histology of the neuroendocrine thymus.
AB  - The primary role of the thymus lies in T-cell differentiation and self-education
      leading to the establishment of appropriate host immune defenses. However, the
      view of the thymus as a self-contained organ is no longer valid. It is now clear
      that intricate interactions of both a stimulatory and inhibitory nature exist
      between the neuroendocrine and immune system. A broad array of neuroendocrine
      circuits are networked with the thymus and neuroendocrine-thymic interactions are
      bidirectional. These interactions are thought to play an important
      immunomodulatory role during an active immune response, during T-cell ontogeny
      and in the aging process of the whole organism. The chemical messengers that
      transmit communicating signals in this network are secreted neuropeptides and
      their specific receptors. The objective of this review is to provide a
      comprehensive overview of the morphological substrates of these neuropeptides in
      the thymus.

PMID- 9264342
TI  - Histopathological features of the Harderian glands in transgenic mice carrying
      MMTV/N-ras protooncogene.
AB  - The Harderian gland is a tubule-alveolar gland found within the orbit, on the
      posterior aspect of the eyeball. In mice, it is composed almost exclusively of
      secretory tubules and alveoli. The Harderian glands of transgenic mice, carrying
      the activated N-ras oncogene under the transcriptional control of the mouse
      mammary tumor virus long terminal repeat promoter (MMTV-LTR), were examined and
      compared to those of normal mice. Thirty transgenic mice provided by A. Pellicer
      (NYU) and 30 normal mice were examined in this study. Harderian glands were
      dissected, immersed in a formalin-based fixative, and embedded in paraffin. The
      sections of these glands were studied via histological techniques. Our results
      show that proliferative alterations in the Harderian glands of these transgenic
      mice are present even in the youngest animals. Such alterations correspond to
      different tumoral evolution stages, ranging from hyperplasia to wide tissue
      destruction. In the most advanced situations, these changes are accompanied by a
      glandular hypertrophy. Our results suggest a very high tumoral incidence in the
      Harderian glands of transgenic mice compared to normal mice. Tumors appear
      spontaneously in some areas, but not at the same time in the whole gland.

PMID- 9264343
TI  - Spray-freezing freeze substitution (SFFS) of cell suspensions for improved
      preservation of ultrastructure.
AB  - Some unicellular organisms present challenges to chemical fixations that lead to
      common, yet obvious, artifacts. These can be avoided in entirety by adapting
      spray-freezing technology to ultrarapidly freeze specimens for freeze
      substitution. To freeze specimens, concentrated suspensions of cells ranging in
      diameter from 0.5-30 pm were sprayed with an airbrush at 140-200 kPa (1.05-1.5
      torr; 20.3-29.0 psi) into a nylon mesh transfer basket submerged in liquid
      propane. After freezing, the mesh basket containing the frozen sample was lifted
      out of the chamber, drained and transferred through several anhydrous acetone
      rinses at 188 K (-85 degrees C). Freeze substitution was conducted in 1% tannic
      acid/1% anhydrous glutaraldehyde in acetone at 188 K (-85 degrees C), followed by
      1% OsO4/acetone at 277 K (4 degrees C). Freeze substitution was facilitated using
      a shaking table to provide gentle mixing of the substitution medium on dry ice.
      High quality freezing was observed in 70% of spray-frozen dinoflagellate cells
      and in 95% of spray-frozen cyanobacterial cells. These could be infiltrated and
      observed directly; however, overall ultrastructural appearance and membrane
      contrast were improved when the freeze-substituted cells were rehydrated and post
      fixed in aqueous OSO4, then dehydrated and embedded in either Spurr's or Epon
      resin. Ultrastructural preservation using this ultrarapid freezing method
      provided specimens that were consistently superior to those obtainable in even
      the best comparable chemical fixations.

PMID- 9264344
TI  - Local immune response in the skin of the external auditory meatus: an
      immunohistochemical study.
AB  - Cerumen plays an important role in the protection of the external auditory meatus
      against several kinds of damage. Its hydrophobic properties, due to the high
      concentration of lipids, shelter the canal from physical damages, while other
      components probably protect against certain microbial strains. Nevertheless there
      has been considerable dispute in the literature with regard to the antibacterial
      activity of cerumen. Because of the importance of the role of immunoglobulins
      (Ig) in local defense mechanisms, we attempted to study, by immunohistochemical
      methods, the presence and localization of the cells necessary to activate an Ig
      mediated immune response and the epithelial expression of immunoglobulin A (IgA),
      immunoglobulin M (IgM), and immunoglobulin G (IgG) in order to obtain information
      about a local immune response in those areas of the skin that take part in
      cerumen production. Our findings indicate that in the human skin of the external
      auditory canal the cells necessary to activate an antibody-mediated immune
      response were localized in the different layers of the epidermis and/or in the
      dermis surrounding the sebaceous and ceruminous glands and the piliary follicle,
      while an intense immunoreactivity for IgA and IgG was observed in the epithelial
      layers of the skin. The results suggest that the external auditory canal is
      protected from the insults of pathogens by an antibody-mediated local immune
      response, because all the effector components of an active local immune system
      are present.

PMID- 9264345
TI  - Acquisition of high-resolution digital images in video microscopy: automated
      image mosaicking on a desktop microcomputer.
AB  - For the digital processing of microscopical images, mosaicking is a prerequisite
      if the specimen is larger than the camera field at the necessary magnification.
      This study investigates the possibilities and limitations of fully automated
      mosaicking on a desktop computer. Cross-correlation-based frame registration was
      performed with high reliability if the video frames were edge-enhanced before
      matched filtering, and also in a reasonable time since the search for matches was
      restricted to pairs of consecutive frames. An environment for routine mosaicking
      was developed and implemented in a widely used desktop image-processing program.
      The software developed during this study has been released to the public domain.

PMID- 9264346
TI  - Low-molecular-weight heparin in the management of Trousseau's syndrome.
AB  - BACKGROUND: Thrombophlebitis migrans is a major cause of morbidity in
      approximately 11% of patients with cancer. Thrombosis may predate the appearance
      of malignancy, and patients with thrombosis often respond poorly to warfarin.
      METHODS: Four patients with extensive thrombosis and cancer are described in this
      article. Enoxaparin, a low-molecular-weight heparin, was administered
      subcutaneously to these patients for 5, 6, 26, and 27 months, respectively. The
      literature on the management of Trousseau's syndrome was reviewed and analyzed.
      RESULTS: All four patients remained free of venous thromboembolism while being
      treated with low-molecular-weight heparin, acutely and during follow-up.
      Previously published studies suggest that therapy with low-molecular-weight
      heparin results in lower mortality than standard heparin therapy. CONCLUSIONS:
      Further study to evaluate the safety and efficacy of low-molecular-weight heparin
      for both prophylaxis and treatment of thromboembolism in association with
      malignancy may lead to decreased morbidity and better quality of life for
      patients with this disorder.

PMID- 9264347
TI  - Neutropenic enterocolitis in a patient with colorectal carcinoma: unusual course
      after treatment with 5-fluorouracil and leucovorin--a case report.
AB  - BACKGROUND: Neutropenic enterocolitis is observed in approximately 25% of
      patients with acute leukemia, but has been reported rarely in patients with solid
      tumors. If treatment is not initiated promptly, the mortality is high. The
      incidence of this disease is rising in patients with hematologic malignancies.
      Increasing numbers of patients with solid tumors are subject to high dose
      chemotherapy regimens or new drugs known to cause severe neutropenia. Therefore,
      the frequency of this disease can be expected to increase. METHODS: The authors
      report a patient with colorectal carcinoma who developed neutropenic
      enterocolitis after treatment with 5-fluorouracil and leucovorin. RESULTS: The
      patient developed the typical clinical picture of abdominal pain, diarrhea, and
      neutropenia. The course was complicated by a recurrence of symptoms after
      initially successful antibiotic therapy without the patient receiving further
      chemotherapy. CONCLUSIONS: This case indicates that neutropenic enterocolitis may
      occur in patients with colorectal carcinoma receiving 5-fluorouracil and
      leucovorin.

PMID- 9264348
TI  - Lymph node spread from carcinoma of the gallbladder.
AB  - BACKGROUND: Lymph node spread is the most common pattern of progression in
      gallbladder carcinoma (GBC) and is a prognostic factor. The purpose of this study
      was to determine the prevalence of lymph node metastases in patients with
      resected advanced GBC, and to evaluate the curative effects of radical surgery
      for patients with lymph node metastasis. METHODS: One hundred and eleven
      consecutive patients who had undergone radical surgery for GBC were included in
      this study. The pattern of lymph node metastases was examined
      histopathologically, using the TNM staging of the American Joint Committee on
      Cancer. RESULTS: There was no neurovascular invasion or lymph node involvement in
      15 patients with pT1 tumors. Sixty of 96 patients with pT2-4 tumors had lymph
      node metastases. The pericholedochal lymph node was the most common metastatic
      lymph node, followed by the cystic lymph node. The frequency of metastases in
      retroportal, posterosuperior pancreaticoduodenal, and interaorticocaval lymph
      nodes was >15% in all cases. pT3-4 tumors had significantly more lymph node
      involvement (79%) and significantly higher N2:N1 ratios (2.5) than pT2 tumors
      (46% and 0.6, respectively). There was no difference in 5-year survival between
      N0 and N1 groups in pT2-4 tumors (66% in N0 and 53% in N1). Patients with N2
      disease had a significantly worse prognosis, but 4 patients survived >5 years.
      CONCLUSIONS: The cystic and pericholedochal lymph nodes are the initial site of
      spread from GBC. The frequency of lymph node involvement is strongly influenced
      by the depth of invasion of the primary tumor. GBC limited to such lymph node
      metastases can be cured by surgery in >50% of such cases.

PMID- 9264349
TI  - Oncogene expression in gastroenteropancreatic neuroendocrine tumors: implications
      for pathogenesis.
AB  - BACKGROUND: Neuroendocrine tumors of the gastroenteropancreatic system include
      pancreatic islet cell and carcinoid tumors. These tumors comprise a functionally
      and biologically heterogeneous group of neoplasms that rarely show reliable
      histopathologic signs of malignancy. No etiologic factors are proven to be
      associated with them, and their exact ontogeny and carcinogenesis remain unknown.
      METHODS: Monoclonal antibodies were employed, along with microwave antigen
      retrieval and the avidin-biotin immunohistochemical method, to investigate the
      expression of c-myc, bcl-2, c-erb B-2, c-erb B-3, c-jun, and proliferating cell
      nuclear antigen (PCNA) in a retrospective series of 116 primary
      gastroenteropancreatic neuroendocrine tumors (GPNTs). The authors attempted to
      correlate this expression with the clinicopathologic outcome of the disease.
      RESULTS: Immunoreactivities for c-myc, bcl-2, c-erb B-2, c-erb B-3, and c-jun
      were detected in 100%, 45%, 24%, 7%, and 24% of pancreatic neuroendocrine tumors
      (PNTs), respectively. In carcinoid tumors, immunoreactivities were detected for c
      myc (63%), bcl-2 (28%), c-erb B-2 (31%), c-erb B-3 (6%), and c-jun (23%). There
      were significantly higher incidences of c-myc, bcl-2, and c-erb B-2
      immunoreactivities in carcinoid tumors of the rectum than in those of the
      appendix, and significantly higher incidences of bcl-2 and c-jun
      immunoreactivities in carcinoid tumors of the bronchus than in those of the
      appendix. Incidence of PCNA immunoreactivity was significantly higher in
      malignant than in benign PNTs and also significantly higher in carcinoid tumors
      of the jejunum and ileum than in those of the appendix. CONCLUSIONS: The
      oncogenes c-myc, bcl-2, c-erb B-2, and c-jun are frequently expressed in human
      GPNTs. The expression of these oncogenes may represent pathogenic events in the
      generation, malignant transformation, and progression of GPNTs. The
      immunohistochemical evaluation of cell kinetics in GPNTs by PCNA might be a
      useful adjunct to conventional diagnostic procedures.

PMID- 9264350
TI  - Utility of screening procedures for detecting recurrence of disease after
      complete response in patients with small cell lung carcinoma.
AB  - BACKGROUND: Studies evaluating the efficacy of routine follow-up testing in
      detecting disease recurrence in treated lung carcinoma patients are lacking.
      METHODS: To investigate this subject, the authors studied 115 patients who had
      previously been entered on North Central Cancer Treatment Group (NCCTG) small
      cell lung carcinoma clinical trials, had achieved a complete response after
      chemotherapy/radiotherapy treatment, and subsequently developed disease
      progression. The authors included 58 patients with limited stage and 57 patients
      with extensive stage disease. Follow-up testing on these clinical trials was
      scheduled at 4-month intervals in the first year and every 6 months thereafter.
      At each visit, testing included a clinical history, physical examination, chest X
      ray, chemistry group, and hematology group. Patients' records were evaluated to
      determine the first test(s) to identify disease recurrence, whether the
      recurrence was diagnosed at the time of routine follow-up or between scheduled
      follow-up evaluations, the sites of recurrence, and patient outcome. RESULTS:
      Recurrences occurred in 56 patients (49%) in the first follow-up year, 51 (44%)
      in the second year, and 8 (7%) after 2 years. Recurrences were signaled by
      clinical histories in 71% of patients, by physical examinations in 10%, chest X
      rays in 12%, and abnormal chemistry testing in 6%. Although 41% of recurrences
      were detected at scheduled clinical visits, 59% of patients had disease
      recurrence signaled by symptoms that prompted interval visits between scheduled
      appointments. At last follow-up, all the patients in this study had died (median
      survival, 115 days [range, 1-793 days] after diagnosis of recurrence), supporting
      the lack of curative therapy for patients with recurrent small cell lung
      carcinoma. CONCLUSIONS: These data, demonstrating that clinical histories and
      physical examinations are the most fruitful means of detecting evidence of
      recurrent lung carcinoma, are consistent with data regarding the follow-up of
      other curatively treated cancers, such as breast carcinoma and melanoma. Chest X
      rays in asymptomatic patients detect recurrences in a small proportion of
      patients, whereas routine blood tests appear to be of little value.

PMID- 9264351
TI  - Primary germ cell tumors of the mediastinum: I. Analysis of 322 cases with
      special emphasis on teratomatous lesions and a proposal for histopathologic
      classification and clinical staging.
AB  - BACKGROUND: Primary germ cell tumors of the mediastinum are unusual neoplasms
      with histopathologic features that are similar to those of germ cell tumors in
      the gonads. However, their clinical features, behavior, and spectrum of
      pathologic features in the mediastinum have not yet been fully defined. METHODS:
      The clinical and pathologic features of 322 cases of primary mediastinal germ
      cell tumors were reviewed, with special emphasis on teratomatous lesions. The
      tumors were divided into groups according to their histologic features and
      correlated with their order of frequency, patient gender and age distribution,
      and morphologic features. A clinical staging scheme based on the extent and
      location of the lesions was devised. RESULTS: The overwhelming majority of
      patients were men (320); only 2 were women (both had teratomatous lesions with
      additional malignant components). The patients' ages ranged from 1 to 79 years
      (mean, 40 years). Histologically, all types of germ cell tumors were represented,
      including 138 teratomas (87 mature teratomas, 6 immature teratomas, and 45
      teratomas with additional malignant components); 120 seminomas; 52
      nonseminomatous, nonteratomatous germ cell tumors (38 yolk sac tumors, 6
      embryonal carcinomas, and 8 choriocarcinomas); and 12 combined germ cell tumors
      without teratomatous components. The teratomatous lesions with additional
      malignant components were further separated into subtypes based on the histologic
      types of their malignant components, i.e., epithelial, mesenchymal, etc. Clinical
      staging was possible in 242 cases, with 191 cases (79%) in Stage I, 4 cases
      (1.6%) in Stage II, and 47 cases (19.4%) in Stage III. In each group, the
      clinical staging correlated well with the clinical outcome for the majority of
      patients. CONCLUSIONS: The results of this study showed that mediastinal germ
      cell tumors have demographic and histopathologic distributions similar to those
      of tumors occurring in the male gonads, with teratomatous and seminomatous
      lesions being the most common. Among the nonseminomatous germ cell tumors in this
      study, the yolk sac tumors appeared to occur the most frequently (the ratio of
      yolk sac tumor occurrence to embryonal carcinoma occurrence was 6.1:1). In
      addition, the subclassification of teratomas with additional malignant components
      based on the histologic types of malignancies may lead to more therapy choices
      for patients. At the same time, the use of a clinical staging scheme may be of
      value in predicting clinical outcome and planning therapy.

PMID- 9264352
TI  - Primary germ cell tumors of the mediastinum: II. Mediastinal seminomas--a
      clinicopathologic and immunohistochemical study of 120 cases.
AB  - BACKGROUND: Primary seminomas of the mediastinum are unusual neoplasms that are
      morphologically indistinguishable from their gonadal counterparts but may have
      different biologic behavior because they arise at this particular location.
      METHODS: The clinical and pathologic features in 120 cases of primary mediastinal
      seminoma were reviewed, and the immunohistochemical staining patterns in 50 of
      these tumors were also analyzed. RESULTS: The patients were all men between the
      ages of 14 and 79 years (mean age, 46.5 years). Their clinical symptoms included
      cough, chest pain, and dyspnea. In some patients, the lesions were asymptomatic
      and discovered incidentally on routine chest radiographs. None of the patients
      had a previous history of testicular neoplasm or tumor elsewhere.
      Macroscopically, the tumors were described as soft and tan, with a slightly
      lobulated cut surface, and measured up to 16 cm in greatest dimension.
      Histologically, the morphologic features were similar to those of tumors
      occurring in the gonads, namely, a neoplastic proliferation of round-to-polygonal
      cells with indistinct cell borders, clear-to-lightly-eosinophilic cytoplasm with
      round-to-oval nuclei and prominent nucleoli, associated with a prominent
      inflammatory background composed mainly of mature lymphocytes. Necrosis,
      hemorrhage, multinucleated giant cells, granulomatous reaction, and remnants of
      thymic tissue were observed in a variable number of cases; mitoses were rare.
      Immunohistochemical studies in 50 cases showed cytoplasmic staining with
      placental alkaline phosphatase in 80% of the tumors, focal dotlike positivity for
      CAM 5.2 low-molecular-weight keratins in 75%, focal cytoplasmic staining for wide
      spectrum keratin in 70%, focal positive reaction with vimentin in 70%, and focal
      positivity with HCG in singly scattered cells in 5%. Immunostains for
      carcinoembryonic antigen, epithelial membrane antigen, and alpha-fetoprotein were
      negative in all the cases studied. Fifty patients were Stage I, 3 patients were
      Stage II, and 12 patients were Stage III. Clinical follow-up information was
      obtained for 65 cases (54%). Forty-nine patients were alive and disease free
      after a period ranging from 1 to 19 years (mean follow-up, 10 years). Sixteen
      patients died within the same period and were found to have metastases to distant
      organs. Of the 16 patients who died, 6 showed extension of the tumor outside of
      the mediastinal compartment at the time of initial diagnosis (Stage III lesions).
      Aside from clinical staging, the authors' findings also suggest that patients >37
      years have worse outcomes than younger individuals. The authors were unable to
      find any correlation between histopathologic features and clinical behavior in
      any of these cases. CONCLUSIONS: Clinical and pathologic staging of mediastinal
      seminomas are important parameters that can be useful in determining the clinical
      outcomes of patients with these tumors. Tumor invasion into adjacent organs
      represents a marker of increased morbidity and mortality. The authors' findings
      suggest that patients with mediastinal seminomas may have a very good prognosis
      when the diagnosis is made early; patients with more advanced lesions may require
      more aggressive therapy for improved local control and prevention of distant
      metastases.

PMID- 9264353
TI  - Primary germ cell tumors of the mediastinum: III. Yolk sac tumor, embryonal
      carcinoma, choriocarcinoma, and combined nonteratomatous germ cell tumors of the
      mediastinum--a clinicopathologic and immunohistochemical study of 64 cases.
AB  - BACKGROUND: Yolk sac tumor (YST), embryonal carcinoma (EC), choriocarcinoma (CC),
      and combined germ cell tumors (CGCTs) of the mediastinum are uncommon neoplasms.
      Only sporadic cases have been documented in the literature; therefore, the
      clinical behavior of these tumors when located in the mediastinum remains
      relatively unknown. METHODS: The clinical and pathologic features of 64 cases of
      primary YST, EC, CC, and CGCTs without teratomatous components were reviewed. The
      immunohistochemical findings in 29 cases were also analyzed using a panel of
      monoclonal and polyclonal antibodies in formalin fixed, paraffin embedded
      tissues. RESULTS: The patients were all men between the ages of 14 and 63 years
      (mean, 38.5 years). Their clinical symptoms included chest pain, shortness of
      breath, chills, fever, and superior vena cava syndrome. None of the patients had
      a previous history of testicular neoplasm or tumor elsewhere. Macroscopically,
      the lesions in 27 patients were described as large, soft, hemorrhagic, and in
      some cases necrotic, and varied in greatest dimension from 6 to 20 cm.
      Histologically, the tumors displayed morphologic features similar to those of
      their gonadal counterparts. Pure YSTs accounted for the majority of cases in this
      series (38 of 64, 60%), followed by pure CCs (8 of 64, 12%) and pure ECs (6 of
      64, 9%). CGCTs accounted for only 18% of the total cases (12 of 64). YSTs showed
      a variety of growth patterns; however, the reticular pattern was the most
      commonly observed. ECs showed a more solid growth pattern with marked
      pleomorphism of the tumor cells and abundant areas of necrosis. CCs were
      characterized by the presence of cytotrophoblastic and syncytiotrophoblastic
      elements with frequent areas of necrosis and hemorrhage. The cases of
      nonteratomatous CGCT consisted of 5 cases of EC + YST, 2 cases of EC + seminoma,
      4 cases of YST + seminoma, and 1 case of EC + CC. In clinical staging, 14
      patients were Stage I, 6 were Stage II, and 19 were Stage III. Information on
      follow-up ranging from 1 month to 13 years was available for 40 patients.
      Seventeen patients with YST died of their tumors. Of these, 10 who presented with
      Stage III disease died within the first 2 years. Unfortunately, no clinical
      staging was obtained for the other 7 patients in this group, and they died within
      6-36 months. It is noteworthy that 4 patients with YST have survived for more
      than 2 years; these patients presented in Stages I and II, and 2 of them received
      aggressive therapy with chemotherapeutic agents and radiation. Two patients with
      Stage III EC died within 2 years. The remaining 4 patients with EC were lost to
      follow-up. Eight patients with CC died within 6 months after initial diagnosis; 7
      of them presented Stage III disease and only 1 presented with Stage I. In the
      nonteratomatous CGCT category, 2 patients with EC + YST died within 2 years after
      initial diagnosis, whereas 3 patients with YST + seminoma were alive after 4-9
      years. CONCLUSIONS: The results of this study confirm the aggressive nature of
      primary nonseminomatous germ cell tumor of the mediastinum; 72% of the patients
      with adequate follow-up died of their tumors within 6-36 months after diagnosis,
      despite aggressive therapy. Clinical and pathologic staging of mediastinal YST,
      EC, and CGCT are important parameters that may be helpful in predicting the
      clinical outcomes of patients with these tumors. The authors' findings suggest
      that the majority of tumors that are not limited to the mediastinum at the time
      of diagnosis have more aggressive behavior. On the other hand, mediastinal
      choriocarcinomas appeared to follow a very aggressive clinical course, regardless
      of treatment modality or clinical tumor stage.

PMID- 9264354
TI  - Prognostic factors in idiopathic (primary) osteomyelofibrosis.
AB  - BACKGROUND: Prognostic variables for idiopathic (primary) osteomyelofibrosis
      (IMF) are ill-defined because of the lack of large control studies based on
      uniform diagnostic criteria. METHODS: A retrospective clinicopathologic study was
      performed on 250 consecutively recruited patients (115 males and 135 females)
      with an established diagnosis of IMF. In contrast to previous studies, the
      current study cohort encompassed the full spectrum of initial to advanced stages
      of the disease process according to laboratory data and particularly histology.
      Because of the relatively high patient age on admission (median, 66.5 years),
      relative survival rates with corresponding life expectancies and disease specific
      life loss were calculated. Moreover, a classification and regression tree (CART)
      analysis was performed to segregate the study patients into subgroups with
      significantly different prognosis. RESULTS: Analysis of the life expectancy and
      the proportion of deaths attributable to IMF showed a global reduction in life
      expectancy of 31%. Further calculation disclosed a consistently greater impact of
      disease in older patients. Age, hemoglobin level on admission, and leukocyte and
      thrombocyte counts remained as the most relevant parameters for prognosis in
      multivariate consideration (CART analysis) and facilitated a clear-cut separation
      into three risk groups. The life expectancy of low risk patients was
      approximately 10 times higher than that of high risk patients (22.07 years vs.
      2.25 years). CONCLUSIONS: These results are in keeping with the assumption that
      features signaling bone marrow insufficiency are associated with a worsening of
      survival. Generalization, indicated by myeloid metaplasia, can occur at every
      stage, even in so-called hypercellular phases of IMF. Conversely, myelofibrosis
      alone is not necessarily predictive of poor survival.

PMID- 9264355
TI  - Impact of menstrual phase on false-negative mammograms in the Canadian National
      Breast Screening Study.
AB  - BACKGROUND: The efficacy of breast carcinoma screening should be enhanced if
      false-negative mammography were reduced. Prospectively collected data from the
      Canadian National Breast Screening Study were used to examine whether menstrual
      cycle phase was associated with false-negative outcomes for mammographic
      screening. METHODS: Of 8887 women ages 40-44 years at the onset of screening,
      randomized to receive annual mammography and clinical breast examination,
      reporting menstruation no more than 28 days prior to their screening examination,
      and with a valid radiologic report, 1898 had never used oral contraceptives or
      replacement estrogen with or without progesterone. The remainder were past (6573)
      and current (416) estrogen users. Similar selection criteria were applied at
      subsequent screens. The distribution of false-negative and false-positive
      mammography in relation to true-negative and true-positive mammography was
      examined with respect to the follicular (Days 1 to 14) and luteal (Days 15-28)
      menstrual phases. RESULTS: Comparing luteal with follicular mammograms in 6989
      patients who ever used estrogen, the unadjusted odds ratio (2-sided P-values) for
      false-negatives versus true-negatives was 2.16 (0.05) and the adjusted odds ratio
      was 1.47 (0.05). In 1898 never-users, parallel odds ratios for luteal false
      negatives were 0.55 (1.0) and 0.74 (1.0), respectively. CONCLUSIONS: These
      results suggest that menstruating women who have used hormones may have an
      increased risk of false-negative results for screening mammograms performed in
      the luteal phase of the menstrual cycle. An increased risk of false-negative
      mammography might adversely affect screening efficacy. The impact of menstrual
      phase on mammographic interpretation, especially for women who ever used
      hormones, requires further investigation.

PMID- 9264356
TI  - Risk factors for breast carcinoma in Singaporean Chinese women: the role of
      central obesity.
AB  - BACKGROUND: The incidence of breast carcinoma in Singapore has nearly doubled
      over the past 25 years. This prospective case-control study involving 1086 women
      (204 cases and 882 controls) was conducted to determine significant factors
      associated with the risk of breast carcinoma among Chinese women in Singapore
      ages 45 to 69 years. METHODS: A forward stepwise logistic regression model
      adjusted for confounding variables of age, age at menarche, menopausal status,
      parity, age at first and last delivery, use of oral contraceptives, hormone
      replacement therapy, family history of breast carcinoma, history of benign breast
      biopsy, smoking history, height, weight, body mass index, and waist to hip ratio
      was used. RESULTS: Central obesity as indicated by women with a larger waist to
      hip ratio was associated with highest risk for breast carcinoma (odds ratio [OR]:
      9.18; 95% confidence interval [CI],4.8-17.5 comparing last and first quintile; P
      < 0.0001, chi-square test for trend). Significant trends were also noted for
      increasing height and breast carcinoma risk (P = 0.003, chi-square test). Women
      who were taller than 159 cm (OR: 2.3; 95% CI, 1.4-3.9) had approximately twice
      the risk of women shorter than 150 cm. Body mass index as a measure of
      generalized obesity did not significantly predict risk for breast carcinoma.
      Reproductive and menstrual factors significantly related to risk for breast
      carcinoma were number of deliveries (OR: 0.81; 95% CI, 0.7-0.9; P < 0.001), age
      at last delivery (P = 0.03), and use of hormone replacement therapy (OR: 0.54;
      95% CI, 0.3-0.9; P = 0.01). Previous breast biopsy for benign disease was also
      associated with a higher risk for breast carcinoma (OR: 3.5; 95% CI, 2.1-5.7; P <
      0.001). CONCLUSIONS: The authors conclude that the risk of breast carcinoma is
      strongly associated with changes in lifestyle related to caloric intake (central
      obesity and height) and reproductive or menstrual factors (number of deliveries,
      age at last delivery, age at menopause, and breast feeding). Better and excess
      nutrition in early and later years of life and fewer births (related to rapid
      urbanization) may explain in part the increasing incidence of breast carcinoma
      occurring in Singapore.

PMID- 9264357
TI  - The effects of postradiation treatment with tamoxifen on local control and
      cosmetic outcome in the conservatively treated breast.
AB  - BACKGROUND: The aim of this study was to evaluate the impact on disease
      recurrence and cosmetic outcome of tamoxifen treatment initiated after breast
      conserving therapy (BCT). METHODS: Between 1982 and 1994, 498 women (509 breasts)
      were treated with BCT in accordance with a highly standardized institutional
      protocol. Adjuvant tamoxifen was administered to 130 patients (134 breasts),
      beginning 1-6 weeks after irradiation. The median ages and duration of follow-up
      for groups who received tamoxifen (TAM+) and no tamoxifen (TAM-) were 62.5
      years/56 months and 53 years/60 months, respectively. The members of the TAM+
      group were significantly older (P = 0.0001) and had increased incidences of
      positive axillary lymph nodes or undissected axilla (P = 0.001). There was a
      significant (P = 0.001) difference between the TAM+ and TAM- groups in the
      distribution of histopathologic subtypes; this reflected an increased proportion
      of associated ductal carcinoma in situ in the TAM- group. More extensive regional
      lymphatic irradiation was administered to the TAM+ group. Chemotherapy was
      administered to 15% of TAM+ and 28% (P = 0.003) of TAM- patients. There were no
      significant differences between the groups with respect to tumor size,
      reexcision, total excised tissue volume, final margin status, total radiation
      dose, or use of interstitial implant boost. RESULTS: There was no significant
      difference between the TAM+ and TAM- groups in the overall distribution of
      cosmetic scores (P = 0.18). The 5-, 7-, and 10-year actuarial local failure rates
      for TAM+ versus TAM- patients were 0% versus 3.1%, 1.9% versus 5.4%, and 1.9%
      versus 8.4%, respectively. Multivariate regression analyses of potentially
      confounding variables revealed no significant associations between tamoxifen and
      either cosmetic outcome or local failure. CONCLUSIONS: Radiotherapy followed by
      tamoxifen has no adverse interactive effect on cosmesis, and tamoxifen is
      associated with a trend toward enhanced 5-year local control probability.

PMID- 9264359
TI  - Prostate carcinoma and long term survival.
AB  - BACKGROUND: The long term survival of patients with prostate carcinoma is not
      well understood. The objective of the current study was to investigate the
      temporal trend of prostate carcinoma mortality in patients who survived > or = 10
      years after diagnosis. METHODS: Men with prostate carcinoma diagnosed from 1958
      through 1983 in the Stockholm/Gotland region in Sweden and who survived > or = 10
      years after the diagnosis were investigated regarding survival beyond 10 years.
      The expected survival was calculated from an annually selected age and time
      matched cohort of men from the general population in the same geographic region.
      The relative survival was expressed as the annual quotient of the observed
      survival over the expected survival. RESULTS: The authors identified 1896
      patients who had survived > or = 10 years. The relative survival decreased up to
      approximately 18 years after the diagnosis, whereupon it reached a plateau that
      was constant up to 30 years after diagnosis. CONCLUSIONS: Men with prostate
      carcinoma surviving > or = 10 years have an excess mortality compared with age
      matched controls. This excess mortality ceases 20 to 23 years after diagnosis and
      the observed and the expected survival are similar, indicating few, if any,
      deaths from prostate carcinoma from there on.

PMID- 9264358
TI  - Angiogenesis in endometrial carcinoma.
AB  - BACKGROUND: Tumor angiogenesis is essential for tumor growth and metastases.
      Recently, microvessel density (MVD), a measure of tumor angiogenesis, has been
      found to have prognostic significance for predicting metastasis and survival in
      many tumor types. This study was conducted to determine how MVD was related to
      several clinicopathologic parameters and correlated with metastasis and survival
      in patients with endometrial carcinoma. METHODS: From 1979 through 1989, 85 cases
      of clinical Stage I and II endometrial carcinomas treated initially by
      hysterectomy with pelvic lymph node dissection were reviewed histologically. All
      hysterectomy specimens were stained immunohistologically for factor VIII-related
      antigen. MVD was counted in a x200 field (x20 objective lens and x10 ocular lens,
      0.785 mm2 per field) in the most active area of neovascularization. Results were
      expressed as the highest number of microvessels identified within any single x200
      field. Statistical analysis included the Mann-Whitney U test, Kruskal-Wallis test
      of variance, and the Spearman rank correlation test. Survival was calculated
      using the Kaplan-Meier method and differences in survival were analyzed using the
      log rank test. MVD and several other prognostic parameters were examined for
      their correlation with progression free survival (PFS) and overall survival (OS)
      by a multivariate analysis according to the Cox proportional hazards model.
      RESULTS: MVD was significantly correlated with tumor grade (P = 0.0281),
      myometrial invasion (P = 0.0282), and lymph-vascular space invasion (P = 0.0073).
      There was no correlation between microvessel count and lymph node status and
      stage. Patients with a high MVD (> or =60) had significantly worse PFS and OS
      than those with a low MVD (<60) (log rank test, P = 0.0116 and P = 0.0096,
      respectively). Multivariate analysis showed that MVD correlated significantly and
      independently with PFS and OS. CONCLUSIONS: In this study, MVD was found to be an
      independent prognostic factor for PFS and OS in patients with endometrial
      carcinoma.

PMID- 9264360
TI  - The prognostic significance of p34cdc2 and cyclin D1 protein expression in
      prostate adenocarcinoma.
AB  - BACKGROUND: Cyclin-dependent kinases (CDK) and cyclins constitute the subunits of
      the maturation-promoting factor that controls the process of cell division. High
      levels of these proteins have been reported in human malignancies of the stomach,
      colon, breast, and lung, and have been implicated in aberrant cell division and
      dysregulated tumor growth. METHODS: p34cdc2 CDK and cyclin D1 (D1) protein
      expression were evaluated in 140 radical prostatectomy specimens harboring
      adenocarcinoma (PAC), using the respective monoclonal antibodies on archival
      tissue sections. In each case, slides stained with hematoxylin and eosin were
      examined for evaluation of Gleason's grade and pathologic stage. The DNA content
      of the tumors was determined by the Feulgen method with the CAS200 Image Analyzer
      (Cell Analysis Systems, Lombard, IL). Nuclear immunoreactivity for the two
      proteins was semiquantitatively scored, and results were correlated with
      Gleason's grade, stage, ploidy, metastatic status, and disease recurrence after
      radical prostatectomy. RESULTS: p34cdc2 was expressed in 84 of 140 PACs (60%) and
      correlated with high Gleason's grade (P = 0.0001), advanced pathologic stage (P =
      0.01), nondiploid DNA content (P = 0.0001), and metastases (P = 0.04). On
      multivariate analysis using the Cox proportional hazards model, p34cdc2
      immunoreactivity (P = 0.0001) and high Gleason's grade (P = 0.01) each
      independently predicted disease recurrence. When tumors were of low Gleason's
      grade and lacked p34cdc2 expression, 4 of 39 PACs (10%) recurred, as compared
      with 18 of 47 (38%) that recurred when tumors were of high Gleason's grade and
      expressed p34cdc2 protein. D1 was positive in 31 of 140 PACs (22%) and showed a
      trend (P = 0.07) of high Gleason's grade, but it did not reach statistical
      significance with any of the prognostic variables. In the majority of PACs
      expressing both p34cdc2 and D1 proteins, the adjacent benign prostate acini
      showed focal, scattered nuclear positivity of the basal and secretory epithelial
      cells. CONCLUSIONS: p34cdc2 is expressed in a majority of PACs and correlates
      with high Gleason's grade, advanced pathologic stage, nondiploid DNA content, and
      metastases. On multivariate analyses high Gleason's grade and p34cdc2
      immunoreactivity predict disease recurrence independently of the pathologic
      stage. Thus, p34cdc2 appears to play a critical role in the evolution,
      proliferation, and spread of PACs and may be of prognostic value when applied to
      initial prostate tissue samples taken by needle biopsy.

PMID- 9264361
TI  - Management of unfavorable locoregional prostate carcinoma with radiation and
      androgen ablation.
AB  - BACKGROUND: This study attempted to define unfavorable locoregional prostate
      carcinoma and presents the results of treatment with combined radiation and
      androgen ablation for these patients. METHODS: Of a group of 938 men with
      clinically localized N0/NX disease treated with radiation alone, an unfavorable
      category included all men with prostate specific antigen (PSA) > 20 ng/mL and all
      men with 10 < PSA < or = 20 ng/mL but with Gleason's grade > 7. One hundred and
      eighty-five such men treated with radiation alone and an additional 100 men with
      similar disease received radiation with early androgen ablation. A second cohort
      was comprised of 229 men with lymphadenectomy proven pelvic lymph node
      metastases, with 185 receiving early androgen ablation alone and 44 receiving
      androgen ablation and local radiation. The outcomes, with recurrence or rising
      PSA as the endpoint, were compared among these various treatment groups using
      multivariate techniques. RESULTS: Disease outcome with the combined modality
      treatment was dramatically improved in both cohorts of men. For those with
      unfavorable N0/NX disease, the failure rate at 5 years decreased from 82% with
      only radiation therapy to 15% with combined treatment. Likewise, for patients
      with lymph node disease, the failure rate at 5 years decreased from 58% with only
      androgen ablation to 10% with combined treatment. For the whole group with
      unfavorable disease (unfavorable N0/NX and lymph node positive disease) the 6
      year failure decreased from 71% with single modality treatment to 13% with
      bimodality treatment. There was a close relationship between the incidence of
      lymph node disease and prognostic categories and patients with otherwise
      unfavorable disease did not have their poor outlook ameliorated by undergoing a
      negative lymphadenectomy. CONCLUSIONS: Unfavorable locoregional prostate
      carcinoma can be recognized on the basis of pretreatment PSA level, T category,
      and Gleason's grade without specific evaluation of pelvic lymph node status.
      Combined local radiation and androgen ablation for patients with unfavorable
      disease results in a substantial improvement in disease control compared with
      that achieved by either modality alone. The authors found no improvement in
      survival because all groups of men had a normal life expectancy to at least 5
      years.

PMID- 9264362
TI  - Expression of the endogenous galactose-binding protein galectin-3 correlates with
      the malignant potential of tumors in the central nervous system.
AB  - BACKGROUND: The 31-kilodalton beta-galactoside-binding protein galectin-3 has
      been associated with cellular transformation and metastasis. Because neural
      tissues contain large amounts of glycoconjugates, and endogenous carbohydrate
      binding proteins have been described in the human brain, the authors examined the
      expression of galectin-3 in human brain tumors and metastases to the central
      nervous system. METHODS: Brain tumors were categorized by the World Health
      Organization system and galectin-3 expression by immunoperoxidase staining using
      a quantitative staining score. RESULTS: Glioblastomas (Grade 4 astrocytomas) all
      stained strongly for galectin-3, whereas low grade astrocytomas (Grade 2) did not
      express the endogenous lectin. Anaplastic astrocytomas (Grade 3) exhibited
      intermediate expression. The staining score was significantly associated with
      tumor grade (P < 0.001). Normal brain tissue and benign tumors did not express
      galectin-3, whereas metastases to the brain were all positive for galectin-3
      expression. Metastases expressed significantly more galectin-3 than the primary
      tumors from which they were derived (P = 0.003). CONCLUSIONS: Galectin-3
      expression correlates with the malignant potential of tumors in the central
      nervous system.

PMID- 9264363
TI  - Kaposi's sarcoma-associated herpesvirus sequences in benign lymphoid
      proliferations not associated with human immunodeficiency virus.
AB  - BACKGROUND: Kaposi's sarcoma-associated herpesvirus (KSHV) DNA sequences have
      been identified in approximately 95% of Kaposi's sarcoma (KS) lesions and primary
      effusion lymphomas (PELs), suggesting a pathogenetic role for this virus in these
      lesions. However, KSHV has also been identified in a variety of specimens,
      including lymph nodes, peripheral blood B cells, semen, and prostate tissue, with
      varying frequencies. This suggests that KSHV, like Epstein-Barr virus, may be
      ubiquitously distributed. To evaluate further the clinical spectrum of KSHV
      infection and define better the prevalence of this virus in lymphoid tissues in
      the general population, the authors examined a wide spectrum of benign lymphoid
      proliferations occurring in human immunodeficiency virus (HIV)-negative
      individuals. METHODS: One hundred eight lymphoid lesions were examined for the
      presence of KSHV by polymerase chain reaction (PCR) amplification using primers
      to open reading frame (ORF) 26. Positive cases were confirmed by Southern blot
      hybridization using an internal oligonucleotide probe and by PCR amplification
      using primers to ORF 74 and ORF 75 of the virus. RESULTS: Only 4 (4%) of 108
      specimens were KSHV positive. Three positive lymph node specimens were taken from
      patients with multicentric Castleman's disease (3 of 11 total cases of
      Castleman's disease; 3 of 5 total cases of multicentric Castleman's disease). The
      remaining case was a lymph node showing paracortical hyperplasia, taken from a
      patient with systemic lupus erythematosus. CONCLUSIONS: KSHV is not detectable by
      PCR technology in a wide range of lymphoid proliferations occurring outside of
      HIV infection. These studies further support the contention that KSHV is
      preferentially associated with KS, PEL, and some cases of multicentric
      Castleman's disease.

PMID- 9264364
TI  - Thyroid dysfunction as a late effect in survivors of pediatric
      medulloblastoma/primitive neuroectodermal tumors: a comparison of
      hyperfractionated versus conventional radiotherapy.
AB  - BACKGROUND: Primary hypothyroidism is a common sequela of craniospinal
      radiotherapy in the treatment of pediatric brain tumors. METHODS: The authors
      compared the incidence of primary hypothyroidism after hyperfractionated
      radiotherapy (HFRT) (n = 14 patients) versus conventionally fractionated
      radiotherapy (CRT) (n = 34 patients) in a group of pediatric patients with
      medulloblastoma/primitive neuroectodermal tumors (MB/PNET). RESULTS: The mean age
      at the time of tumor diagnosis was 7.9 years in the HFRT group and 8.4 years in
      the CRT group. The patients were followed for a mean of 4.6 years (HFRT) and 8.3
      years (CRT) after diagnosis. Mean radiation doses to the thyroid were similar in
      both radiotherapy groups (29 gray [Gy] [HFRT] vs. 24 Gy [CRT]). Approximately 14%
      of the HFRT and 62% of the CRT patients developed primary hypothyroidism within a
      similar period after irradiation (3.2 years [HFRT] vs. 3.0 years [CRT]). Analysis
      by cumulative incidence function demonstrated a significant difference in the
      risk of developing thyroid dysfunction between these two groups of patients (P =
      0.02). CONCLUSIONS: The current study findings suggest that the use of HFRT in
      the treatment of pediatric patients with MB/PNET is associated with a lower risk
      of these patients developing primary hypothyroidism.

PMID- 9264365
TI  - The National Cancer Data Base report on carcinoma of the anus.
AB  - BACKGROUND: The last 15 years have seen substantial advances in the management of
      anal carcinoma, primarily in the use of radiochemotherapy as definitive or
      adjuvant treatment. This study reviews the patterns of presentation, care, and
      outcome reflected in data from the National Cancer Data Base representing a broad
      range of medical centers. METHODS: Data on patients with anal carcinoma (on 1050
      patients from 1988 and 1289 patients from 1993) were reviewed for patterns of
      care and presentation. The 1988 cases were also reviewed for outcome data.
      RESULTS: There was an increase in the use of chemotherapy between 1988 and 1993
      (from 61.6% to 67.2%), and substantial differences were observed in the
      management of epidermoid carcinomas and adenocarcinomas. The majority of
      epidermoid carcinomas were managed nonsurgically, principally with combined
      chemotherapy and radiation, whereas three-fourths of patients with adenocarcinoma
      underwent surgery. The most important factors for favorable 5-year survival were
      early stage (ranging from 71.3% for Stage I to 23.1% for Stage IV), epidermoid
      carcinoma histology (57.6%, compared with 41.3% for adenocarcinoma), and female
      gender (56.2%, compared with 49.6% for males). For Stage I-II epidermoid
      carcinomas, the 5-year survival for patients who received nonsurgical treatment
      with radiochemotherapy was equivalent to that of patients who received surgical
      treatment (64.0% and 65.4%, respectively). CONCLUSIONS: This study confirms a
      trend in patterns of care favoring nonsurgical management with radiochemotherapy
      for epidermoid carcinomas of the anus. For adenocarcinomas, there has been a
      trend toward increasing use of multimodality therapy with surgery and adjuvant
      radiochemotherapy. Survival data from the 1988 cases confirmed the efficacy of
      conservative treatment with radiation plus chemotherapy for epidermoid
      carcinomas.

PMID- 9264366
TI  - The National Cancer Data Base report on malignant epithelial ovarian carcinoma in
      African-American women.
AB  - BACKGROUND: Epithelial ovarian carcinoma is the fifth most common cause of cancer
      death among African-American women. Although the incidence rate of ovarian
      carcinoma for whites is higher than that for African Americans, the relative
      survival rate for African Americans is poorer. METHODS: Data were cases submitted
      to the National Cancer Data Base for invasive epithelial tumors of the ovary
      diagnosed between 1985-1988 and 1990-1993. African-American women with epithelial
      ovarian carcinoma were compared with non-Hispanic white women with the same
      disease. The groups of white women with which African-American women were
      compared were classified as "White-same facility" and "White-other facility."
      "White-same facility" were white patients from hospitals that contributed a
      substantial proportion of African-American patients. "White-other facility" were
      white patients from hospitals that contributed few or no African-American
      patients. No patient had a history of prior cancer. RESULTS: African-American
      women with advanced invasive epithelial ovarian carcinoma were less often treated
      with combined surgery and chemotherapy and more often treated with chemotherapy
      only. African-American women were twice as likely as white women not to receive
      appropriate treatment. African-American women had poorer survival rates than
      white women from the same or different hospitals, regardless of income. Among
      staged cases, African-American women were more often diagnosed with Stage IV
      disease than either group of white women. CONCLUSIONS: The current study findings
      show that African-American women with advanced epithelial ovarian carcinoma
      received less aggressive treatment than white women and had a poorer prognosis.

PMID- 9264367
TI  - Smad5, a tumor suppressor candidate at 5q31.1, is hemizygously lost and not
      mutated in the retained allele in human leukemia cell line HL60.
AB  - Deletions of the long arm of chromosome 5 with common overlapping segment 5q31.1
      are among the most frequent cytogenetic aberrations in myelodysplastic syndromes
      and acute myeloid leukemias (MDS/AML). We have constructed a YAC-based physical
      map of the 5q31.1 critical locus and localized the transcriptional transactivator
      Smad5 adjacent to loci showing consistent loss of heterozygosity in these
      disorders. Smad5 plays a key role along the bone morphogenetic protein-4 (BMP-4)
      inhibitory signalling pathway inducing embryonic hematopoiesis. Smad5 homologs
      Smad2 and DPC4 have recently been linked to human cancer. FISH analysis of AML-M2
      cell line HL60 and of four MDS/AML patients revealed consistent hemizygous loss
      of the Smad5 locus. In HL60 cells, a translocation event within 5q31.1 associated
      with loss of adjacent material leads to disruption of the critical locus with
      partial retention of the 5q31.1 genomic sequences on a marker chromosome. RT-PCR
      sequencing analysis of the HL60 Smad5 remaining allele ruled out the functional
      inactivation of the gene analogous to that occurring in the Smad5 homologs DPC4
      and Smad2 in cases of pancreatic and colorectal cancers. Mutational analysis of
      Smad5 in MDS/AML cases is in progress.

PMID- 9264368
TI  - The use of an all oral chemotherapy (idarubicin and etoposide) in the treatment
      of acute myeloid leukaemia in the elderly: a report of toxicity and efficacy.
AB  - Acute myeloid leukaemia (AML) is predominantly a disease of the elderly but such
      patients are not always appropriate candidates for intensive intravenous (i.v.)
      based treatment regimens. The development of the anthracycline idarubicin which
      is highly effective in the treatment of AML and is active when given orally has
      made it possible to design anti-leukaemic regimens which may be given orally and
      be particularly useful in those elderly patients with AML considered unsuitable
      for standard intensive aggressive treatments. We have assessed an oral regimen
      combining idarubicin 30 mg/m2 and etoposide 80 mg/m2 for 3 consecutive days as
      initial treatment in 28 elderly patients with AML (median age 69 years, range 56
      81) who were not considered suitable for more intensive i.v. chemotherapy
      schedules. Following informed consent, two patients died before treatment began
      and one patient withdrew prior to treatment. Twenty-five patients underwent one
      to four courses of treatment. The schedule was well tolerated with minor
      nonhaematological toxicity. The first course was given in hospital, eight of 21
      subsequent courses of treatment were given entirely as an out-patient. Eleven
      patients responded to treatment with nine (36%) achieving complete remission
      (CR). The median survival for all patients was 3 months, but for the nine who
      achieved a CR it is 9 months with six patients still alive, five in first CR and
      one in second CR. We conclude that a combination of idarubicin and etoposide
      given orally as first-line treatment in elderly patients with AML is safe and
      effective. In some patients this means treatment and follow-up can be given
      entirely on an out-patient basis.

PMID- 9264369
TI  - Cranial irradiation is the major cause of learning problems in children treated
      for leukemia and lymphoma: a comparative study.
AB  - Prophylactic treatment of the central nervous system (CNS) in childhood leukemia
      and non-Hodgkin lymphoma (NHL) has negative effects on intelligence. We
      investigated the clinical significance of this finding by comparing the effect of
      different types of CNS prophylaxis on the survivor's learning capabilities. To
      isolate the effect of different types of CNS prophylaxis from other treatment and
      disease variables on learning problems, children treated for leukemia or NHL who
      received CNS prophylaxis with cranial irradiation (n = 30) or without cranial
      irradiation (n = 36) were compared with children treated for solid tumors who
      received systemic chemotherapy without any CNS treatment (n = 30) and with
      matched healthy controls (n = 265). The identification of learning problems was
      based on the school system's assessment. Parents and teachers reported on the
      child's educational status in a standardized way. Learning problems were found in
      80% of children who received CNS prophylaxis with cranial irradiation. This was
      significantly higher than the 14% found in children treated with CNS prophylaxis
      without cranial irradiation (P < 0.000). The prevalence of learning problems in
      this latter group did not differ significantly from that in childhood cancer
      survivors without any form of CNS prophylaxis (20%) and in healthy matched
      controls (17%). We conclude that the high prevalence of learning problems in
      survivors of childhood leukemia and NHL is directly related to CNS prophylaxis
      with cranial irradiation and not to CNS prophylaxis per se or to other treatment
      and disease variables.

PMID- 9264371
TI  - Deletion of chromosome arm 3p in hematologic malignancies.
AB  - Cytogenetic aberrations resulting in deletion of 3p are common in solid tumors,
      indicating the presence of tumor suppressor genes (TSG) on this chromosome arm.
      The present study was undertaken to investigate 3p loss in hematologic disorders.
      Ten acute myeloid leukemias (AML), two myelodysplastic syndromes (MDS), one
      Philadelphia chromosome-positive chronic myeloid leukemia (CML), three acute
      lymphoblastic leukemias (ALL), one chronic lymphoproliferative disorder (CLD),
      and three non-Hodgkin's lymphomas (NHL) with abnormalities leading to 3p
      deletions were identified, constituting 2.9% of AML, 0.7% of MDS, 1.0% of CML
      with changes in addition to t(9;22), 1.5% of ALL, 4.2% of CLD, and 1.1% of NHL
      with cytogenetic abnormalities analyzed at our Department. Among 19042
      karyotypically aberrant published cases, 1.2% of 6260 AML, 1.3% of 2285 MDS, 0.8%
      of 840 chronic myeloproliferative disorders (CMD), 0.7% of 1894 CML with
      additional aberrations to t(9;22), 0.6% of 3589 ALL 2.4% of 1602 CLD, 4.5% of 178
      Hodgkin disease (HD), and 3.1% of 2394 NHL displayed partial loss of 3p (0.6
      4.5%; P < 0.001); the majority occurring together with other abnormalities. The
      frequencies of 3p loss did not differ significantly among the MDS, ALL, and CLD
      morphologic subgroups, between B and T cell ALL, CLD, and NHL, among low-,
      intermediate-, and high-grade NHL, or between therapy-related MDS and de novo
      MDS, whereas the incidence of 3p deletions was higher in treatment-associated AML
      (P < 0.001) than in de novo AML and varied among the AML FAB groups (P < 0.001).
      The most frequently deleted chromosome bands were 3p25 in AML, 3p26 in MDS, 3p14
      in CMD, 3p25, 3p23, and 3p21 in CML, 3p26 and 3p25 in ALL, 3p26 and 3p25 in CLD,
      3p26 in HD, and 3p26 in NHL. These deletion hot spots are more distal than those
      reported in most solid tumor types, suggesting that different TSG are involved in
      hematologic malignancies and solid neoplasms.

PMID- 9264370
TI  - Genetic studies of childhood acute lymphoblastic leukemia with emphasis on p16,
      MLL, and ETV6 gene abnormalities: results of St Jude Total Therapy Study XII.
AB  - To determine the frequency and prognostic significance of recently described
      genetic lesions in pediatric acute lymphoblastic leukemia (ALL), all cases with
      available leukemic cell samples treated on St Jude Study XII were analyzed by
      molecular techniques for alterations of the p16, MLL and ETV6 genes. Homozygous
      p16 deletion was seen in 36 of 155 cases, including 14 of 23 T cell cases, but
      had no prognostic value. Rearrangement of MLL was seen in nine of 170 cases (5%)
      and conferred a poor prognosis, with a 5-year EFS estimate of only 11 +/- 7%,
      compared with 74 +/- 5% for the germline MLL group (P=0.0001). By contrast,
      rearrangement of ETV6 was found in 35 cases (21%) and was significantly
      associated with a better outcome (5-year EFS estimates: 87 +/- 7% vs 64 +/- 6%).
      In a Cox regression model adjusted for age, DNA index, race, leukocyte count,
      treatment group, and CNS status, ETV6 rearrangement retained independent
      prognostic significance (two-sided P value 0.012). Thus, in this uniformly
      treated group of patients, we confirmed the unfavorable prognostic significance
      of MLL rearrangement and demonstrated the favorable impact of ETV6 rearrangement,
      suggesting that these factors be added to ALL risk classification schemes.

PMID- 9264372
TI  - Involvement of a human endogenous retroviral sequence (THE-7) in a
      t(7;14)(q21;q32) chromosomal translocation associated with a B cell chronic
      lymphocytic leukemia.
AB  - B cell chronic lymphocytic leukemias (B-CLL) like other blood cell malignancies
      are characterized by chromosomal anomalies directly involved in tumor
      pathogenesis. We report here the molecular characterization of a t(7;14)(q21;q32)
      chromosomal translocation observed during the course of a B-CLL. We show that
      this translocation led to the juxtaposition of the immunoglobulin heavy chain
      locus on chromosome 14 to an endogenous retroviral sequence belonging to the THE
      family (transposable-like human element) on chromosome 7q21. RT-PCR analysis
      demonstrated that this sequence is transcribed in most of the tumoral and normal
      tissue analyzed and in the B-CLL described here. These data raise the question of
      the role of transposable elements in the pathogeny of some leukemias or at least,
      in the occurrence of chromosomal rearrangements. Structural rearrangements of the
      7q21-22 region are frequently encountered in myeloid disorders, and the work
      presented here could help in their characterization.

PMID- 9264373
TI  - TEL is one of the targets for deletion on 12p in many cases of childhood B
      lineage acute lymphoblastic leukemia.
AB  - Abnormalities of the short arm of chromosome 12 including loss of heterozygosity
      (LOH) and TEL/AML-1 fusion resulting from a t(12;21)(p13;q22) translocation are
      frequently observed in childhood acute lymphoblastic leukemia (ALL). We
      investigated 21 DNA samples of childhood ALL which had LOH at 12p13.
      Rearrangement of TEL was observed in eight cases and another case showed a
      homozygous deletion of TEL. Two informative samples with TEL rearrangement had a
      deletion localized to the 5' region of this gene. The deletion in these two cases
      includes the helix-loop-helix (HLH) domain. This is consistent with the
      hypothesis that the normal tel can heterodimerize with the TEL/AML-1 gene product
      and inhibit the transforming capacity of the chimeric protein. Presumably, loss
      of the HLH of the normal remaining TEL allele abrogates this tumor suppressor
      like function. The case with homozygous deletion of TEL is also consistent with
      this gene having qualities of a tumor suppressor. One unusual case had T-ALL
      rather than B-lineage ALL and the leukemic cells had rearrangement of TEL, but
      they did not have an alteration of the remaining TEL allele suggesting that the
      etiology of this disease may be different. This analysis further emphasizes the
      importance of loss of the normal TEL allele in childhood precursor B-lineage ALL.

PMID- 9264374
TI  - ETS-1 induces increased expression of erythroid markers in the pluripotent
      erythroleukemic cell lines K562 and HEL.
AB  - Members of the ETS gene family are known to be expressed in hematopoietic tissues
      and cell lines, and there is increasing evidence that ETS proteins may play a
      role in normal hematopoietic cell development. We demonstrate that ETS-1 can
      contribute to the development of an erythroid phenotype in vitro. The pluripotent
      erythroleukemic K562 and HEL cell lines express messages for a number of ETS
      genes, but only c-ETS-1 levels are elevated in response to treatment with hemin
      or cytosine arabinofuranoside (Ara-C), agents which induce erythroid
      differentiation. Furthermore, ETS-1 antisense oligonucleotides inhibit
      hemoglobinization of cells treated with Ara-C or hemin, and K562 and HEL cells
      infected with retrovirus expressing the c-ETS-1 gene exhibit a significant
      increase in erythroid character (as indicated by benzidine staining for
      hemoglobin (Hb) and surface marker analysis), a dramatic increase in
      responsiveness to hemin or Ara-C, and a decreased rate of proliferation (20-40%
      of control rates). In contrast, infection with virus expressing ETS-2 or vector
      sequences only causes no detectable changes in the proliferation or erythroid
      character of either the HEL or K562 cell lines. These data indicate a role for
      ETS-1 in erythroid differentiation.

PMID- 9264375
TI  - Expression of FLT4 and its ligand VEGF-C in acute myeloid leukemia.
AB  - FLT4 represents a recently cloned member of class III receptor tyrosine kinases
      which include receptors for the angiogenic growth factor VEGF, namely FLT1 and
      KDR. The ligand of FLT4 has been identified as VEGF-C which shares sequence
      homology with VEGF and P1GF. In the adult FLT4 shows a restricted expression
      pattern that is limited to lymphatic endothelia and endothelia of some high
      endothelial venules (HEV). FLT4 has also been detected in some tumor cell lines
      including the hematopoietic line HEL. We therefore investigated expression of
      FLT4 and its ligand VEGF-C in fresh samples from patients with AML. Using a
      sensitive PCR method we detected FLT4 m-RNA in 15 of 41 patients with de novo AML
      at diagnosis or relapse and in three of 12 patients with secondary AML. FLT4
      expression was confirmed by immunocytochemistry in a subgroup of the studied
      patient population. FLT4 was also found in leukemic cell line U937, but not TF-1
      and KG1a. VEGF-C expression was found in leukemic samples of four of seven FLT4
      positive and four of six FLT4-negative patients. U937 cells also produced VEGF-C
      m-RNA. Interestingly, FLT4 expression was not detected in bone marrow samples of
      15 normal volunteer donors or in CD34-positive cells from three additional
      donors. Possible autocrine and paracrine growth stimulation of leukemic blasts by
      VEGF-C is currently being investigated in our laboratory.

PMID- 9264376
TI  - Camptothecin-induced apoptosis in p53-null human leukemia HL60 cells and their
      isolated nuclei: effects of the protease inhibitors Z-VAD-fmk and
      dichloroisocoumarin suggest an involvement of both caspases and serine proteases.
AB  - The human leukemia cell line, HL60 is very sensitive to various apoptotic stimuli
      and p53-null. The death-related cysteine proteases of the caspases family play a
      central role in the execution phase of apoptosis, and we recently reported the
      importance of serine protease activation in camptothecin-induced apoptotic
      endonuclease activation in HL60 cells. In the present study, we investigated the
      role of caspases (ICE/CED-3-related cysteine proteases) and serine proteases in
      cell death induced by the topoisomerase I inhibitor, camptothecin, in HL60 cells
      and in a cell-free system. We found that CPP32 is activated during camptothecin
      induced apoptosis, and that N-benzyloxycarbony-Val-Ala-Asp (O-methyl) 
      fluoromethyketone (Z-VAD-fmk), a cell permeable caspase inhibitor blocks all
      features of apoptosis: morphological changes, cleavage of caspase 3
      (CPP32/Yama/Apopain) and poly(ADP-ribose) polymerase, lamin B degradation and DNA
      fragmentation. However, Z-VAD-fmk and two other ICE/CED-3 inhibitors, YVAD-CHO
      and DEVD-CHO, were inactive in a cell-free system reconstituted from nuclei of
      untreated HL60 cells and cytosol from camptothecin-treated cells, suggesting that
      caspases are not required for endonuclease activation or lamin B cleavage in the
      cell-free system. By contrast, the serine protease inhibitors, 3,4
      dichloroisocoumarin (DCI) and L-1-chloro-3-(4-tosylamido)-4-phenyl-2-butanone
      tosyl-L-phenylalanine chloromethyl ketone (TPCK), abolished the apoptosis
      associated biochemical changes induced by camptothecin both in whole cells and in
      a cell-free system. DCI also inhibited CPP32 cleavage. Taken together, these
      results suggest that in HL60 cells, both CPP32 and serine proteases are activated
      in camptothecin-induced apoptosis.

PMID- 9264377
TI  - Differential CD95 expression and function in T and B lineage acute lymphoblastic
      leukemia cells.
AB  - CD95 (Fas/APO-1) is a cell surface receptor able to trigger apoptosis in a
      variety of cell types. The expression and function of the CD95 antigen on
      leukemic blasts from 42 patients with B lineage and 53 patients with T lineage
      acute lymphoblastic leukemia (ALL) were investigated using immunofluorescence
      staining and apoptosis assays. The CD95 surface antigen was expressed in most ALL
      cases, with the T lineage ALL usually showing a higher intensity of surface CD95
      expression as compared with the B lineage ALL cells (relative fluorescence
      intensity, RFI: 4.8 +/- 0.47 vs 2.2 +/- 0.23, respectively, P < 0.01). Functional
      studies disclosed that upon oligomerization by anti-CD95 monoclonal antibodies
      the CD95 protein was either not able to initiate apoptosis of leukemic cells (75%
      of cases) or induced low rates of apoptosis (20% of cases). Only in 5% of cases
      did the apoptosis rate exceed the 20% level of the CD95-specific apoptosis. Most
      of the CD95-sensitive cases were found among T lineage ALLs (38% of T lineage vs
      10% of B lineage ALLs). Overall, the extent of CD95-induced apoptosis did not
      correlate with the expression level of CD95. Similarly, no significant
      correlation between expression level and functionality of CD95 in human leukemia
      cell lines of B and T cell origin could be observed. Bcl-2 protein has been
      associated with prolonged cell survival and has been shown to block partially
      CD95-mediated apoptosis, but for ALL cells no correlation between bcl-2
      expression and spontaneous or CD95-mediated apoptosis could be found. The results
      obtained in this study indicate that, despite constitutive expression of CD95,
      the ALL cells are mainly resistant to CD95-triggering. More detailed
      investigations of the molecular mechanisms involved in the intracellular
      apoptotic signal transduction, such as interactions of the bcl-2 and the other
      members of the bcl-2 family, and functionality of the interleukin-1beta
      converting enzyme (ICE) like-proteases, may give new insights into key events
      responsible for the resistance or sensitivity to the induction of apoptosis in
      acute leukemia.

PMID- 9264378
TI  - Induction of apoptosis by 2-chlorodeoxyadenosine in B cell chronic lymphocytic
      leukemia.
AB  - We investigated whether 2-chlorodexoyadenosine could induce apoptosis in B cell
      chronic lymphocytic leukemia (B-CLL) cells in vitro using clinically achievable
      drug doses, measuring apoptosis ratio by flow cytometry. B cells were isolated
      from previously untreated patients and apoptosis was measured in these cells
      immediately after isolation and following incubation in vitro, without and with 2
      chlorodeoxyadenosine at different concentrations, for 24 and 48 h. Distribution
      of cellular DNA content and quantitative analysis of apoptosis were determined by
      standard propidium iodide staining and flow cytometry. Spontaneous apoptosis
      occurred in B-CLL cells incubated in vitro in the absence of drug, but the level
      of apoptosis was greater in cells treated with 2-chlorodeoxyadenosine after the
      second day of culture. The present in vitro study of B-CLL cells from previously
      untreated patients suggests this chemotherapeutic agent activates a program of
      cell death by apoptosis using a drug dose equivalent to the physiological
      concentration used in patients in vivo. These data reveal an interesting
      possibility in the 2-chlorodeoxyadenosine treatment of untreated patients by
      neoplastic B cell apoptosis induction.

PMID- 9264379
TI  - Rearrangement status of the malignant cell determines type of secondary IgH
      rearrangement (V-replacement or V to DJ joining) in childhood B precursor acute
      lymphoblastic leukemia.
AB  - Immunoglobulin heavy chain (IgH) oligoclonality in childhood B precursor acute
      lymphoblastic leukemia (ALL) as determined by Southern analysis is found in 30
      50% of patients and has been shown to be the result of ongoing IgH rearrangement
      (mostly V(H)-replacement and V(H) to D-J(H) joining) after malignant
      transformation. It is unknown however, what determines the type of secondary
      rearrangement. Also the biological basis of the variable degree of oligoclonality
      observed in childhood ALL is poorly understood. We analyzed in detail the IgH
      rearrangement status of the leukemic cells for a random panel of 18 childhood B
      precursor ALL patients by polymerase chain reaction (PCR)/sequencing analysis and
      by Southern analysis. By Southern analysis 10/18 (55.6%) patients were considered
      oligoclonal and 8/18 (44.4%) monoclonal. In contrast, by PCR minor clonal
      rearrangements were detected in 14/18 (77.8%) patients. V(H)-replacement was
      found in 7/14 patients, V(H) to D-J(H) joining in 6/14 patients and an unusual
      type of secondary rearrangement, V(H)-D to J(H) joining, in one patient. Only a
      single type of secondary rearrangement was detected in each patient. The type of
      secondary rearrangement (V(H)-replacement or V(H) to D-J(H) joining) depended on
      the rearrangement status (VDJ/VDJ or VDJ/DJ, respectively) of the dominant
      leukemic clone as determined by Southern analysis. We found that in addition to a
      more 'advanced' IgH rearrangement status patients with V(H)-replacements also
      have a more 'advanced' TCRdelta rearrangement status, which possibly reflects
      exposure of both the IgH locus and the TCRdelta locus to recombinase activity in
      a preleukemic clone. Finally, we investigated a putative relationship between
      oligoclonality by Southern analysis and S-phase fraction of the leukemic cell
      population. We found a significantly lower percentage cells in S-phase for
      oligoclonal patients as compared to monoclonal patients. Our data add to the
      understanding of ongoing rearrangement of antigen receptor loci in childhood ALL
      and have implications for the monitoring of minimal residual disease by PCR.

PMID- 9264380
TI  - Multiparameter phenotype mapping of normal and post-chemotherapy B lymphopoiesis
      in pediatric bone marrow.
AB  - We studied the differentiation profiles of B cell precursors (BCP) in normal and
      post-chemotherapy pediatric bone marrow (BM) using multiparameter flow cytometry.
      The goal of our study was to draw a comprehensive phenotypic map of the three
      major maturational BCP stages in BM. By correlating lineage-associated markers,
      CD45RA, and several adhesion molecules, the stage-specific patterns were found to
      differ in certain details from previously published concepts. Among the earliest
      BCP, a subset of CD34+ CD10(lo) precursors was repeatedly observed in addition to
      the well characterized CD34+ CD10(hi) CD19+ majority of cells. Only two-thirds of
      these CD34+ CD10(lo) cells expressed CD19. However, uniformity of phenotypic
      features, absence of T lineage markers, and the regeneration kinetics after
      chemotherapy suggest the B lineage affiliation of the CD34+ CD10(lo) precursors
      in general. In the more mature BCP, expression of CD10, CD20, cytoplasmic and
      surface mu chains (c mu and s mu) was observed to overlap more than previously
      recognized. We found that CD20 and c mu appear early during B cell ontogeny
      (already on CD34+ BCP), and that CD10 is lost late, following the onset of s mu
      expression. Differences between normal and post-chemotherapy BM specimens
      regarding the phenotypic appearance of BCP were exclusively due to differences in
      the subset composition, as post-chemotherapy samples showed a preponderance of
      immature stages. Our observations may build a framework for comparing leukemic
      cells with their normal counterparts to define possible leukemia-associated
      aberrations useful for residual disease studies.

PMID- 9264381
TI  - Comparison of the immunoglobulin gene transcripts between immature B lineage
      acute lymphoblastic leukemia and the normal phenotypic counterparts in the bone
      marrow.
AB  - Immature B lineage acute lymphoblastic leukemia (ALL) is divided into two
      subtypes, 'pre-B' and 'early pre-B' ALL, by the presence or absence of
      cytoplasmic immunoglobulin (cIg). To study their clonal origin, we compared mu
      chain transcripts in six cIg+ and eight cIg- ALL samples (CD10+/- CD19+ surface
      Ig-) with those in the normal phenotypic counterparts (CD10+ CD19+ surface Ig-)
      sorted from the bone marrow (BM). Northern blot analysis showed that the cIg+ ALL
      samples expressed greater amounts of mu-chain transcripts than the cIg- ALL
      samples. In the ALL samples and their counterparts, sequence analysis of mu-chain
      transcripts revealed infrequent somatic mutations of the V(H) genes and the
      similar usage of D and J(H) gene segments, but the length of complementarity
      determining region (CDR)-3 in the ALL samples was longer than that in the
      counterparts (50.0 +/- 15.5 vs 40.8 +/- 12.7 bp, P = 0.01). The mu-chain
      transcripts in the six cIg+ ALL samples and the counterparts (119/120 clones) had
      productive sequences, whereas those in the eight cIg- ALL samples had nonsense
      codons and/or frame shifts in their CDR-3. Our data suggest that a phenotype of
      ALL, 'pre-B' or 'early pre-B', is associated with V(H)-D-J(H) gene
      recombinatorial events, and that the CD10+ CD19+ surface Ig- population in the BM
      is not simply the cellular origin of ALL.

PMID- 9264382
TI  - Does transmembrane communication through gap junctions enable stem cells to
      overcome stromal inhibition?
AB  - When long-term bone marrow cultures are treated with Amphotericin B (AB) their
      haemopoietic stem cells (HSC) cease growing. This is not a toxic effect of the
      drug because once that is removed, HSC resume clonal growth and, given sufficient
      time, form as many cells as HSC in untreated cultures. Amphotericin B-evoked
      inhibition of blood formation is probably mediated by transmembrane communication
      between HSC and stroma for the following reasons: (1) AB does not stop HSC
      forming colony-forming units in culture (CFU-c) when HSC are separated from
      stroma by culturing them on Transwell inserts above the stroma. (2) Conditioned
      media (CM) from AB-containing or normal long-term cultures (LTC) does not inhibit
      normal marrow cells forming colonies in semi-solid cultures without stromal
      underlays. (3) AB itself does not stop bone marrow cells forming colonies in semi
      solid cultures nor does it stop stromal cells growing or prejudice their long
      term maintenance. (4) Furthermore, growing stromal cells with AB does not alter
      the number of transcripts they form for cytokines and chemokines to any large
      extent, including TGF-beta1. We have extensive, though circumstantial, evidence
      that gap junctions are involved in this communication. AB only stopped the growth
      of HSC when we blocked intercellular communication via gap junctions (GJIC)
      (tested by micro-injection of lucifer yellow). Lipophilic compounds that do not
      affect GJIC had no effect on the growth of HSC. Looking at a series of stromal
      cell lines from foetal liver and neonatal bone marrow we found that extensive
      GJIC correlated with stromal support of the late-appearing clones formed by
      primitive HSC (week 3-5 cobblestone-area forming cells, CAFC). We propose that
      the proliferation of HSC is regulated via transmembrane communication between
      stromal and HSC. Our findings support the proposal that gap junctions play a part
      in this stromal-dependent regulation.

PMID- 9264383
TI  - Upregulation of CD9 expression during TPA treatment of K562 cells.
AB  - The CD9 antigen, a major platelet glycoprotein, is a member of the tetraspan
      superfamily. We show that treatment of K562 cells with 12-O-tetradecanoylphorbol
      13-acetate (TPA) which induces megakaryocytic differentiation, leads to a seven
      fold increase in CD9 expression, which becomes associated with the integrin
      beta1, suggesting that it is functionally relevant. The upregulation of CD9
      expression precedes the appearance of the megakaryocytic-specific marker GPIIb
      (CD41) as well as integrins beta3 (GPIIIa/CD61), alpha v (CD51) and VLA-2
      (CD49b). Both GPIIb/IIIa expression and CD9 upregulation are dependent on protein
      kinase C (PKC) activation since they are blocked by the specific inhibitor
      GF109203X. Steady-state levels of CD9 and GPIIb mRNA were also measured by
      quantitative RT-PCR. Both messengers were detected on resting cells and were
      shown to accumulate during TPA treatment. However, the increase of the CD9 mRNA
      was detected much earlier than the increase of GPIIb mRNA (1-2 h vs 24-48 h).
      Using different constructs of the 5'-flanking domain of the CD9 gene cloned ahead
      of the CAT reporter gene, we could demonstrate that a responsive element was
      located in a 52 bp fragment of the promoter of the CD9 gene. Altogether, these
      data suggest that CD9 upregulation in the megakaryocytic lineage could occur at
      early stages of differentiation.

PMID- 9264384
TI  - Interleukin-15 + thioredoxin induce DNA synthesis in B-chronic lymphocytic
      leukemia cells but not in normal B cells.
AB  - We have previously shown that Staphylococcus aureus Cowan strain 1 particles
      (SAC) + thioredoxin (Trx) + IL-2 may induce B-chronic lymphocytic leukemia (B
      CLL) cells to proliferate. In this paper we have examined IL-15, which has
      activities similar to IL-2, for its ability to stimulate B-CLL cells and compared
      its activity with that of IL-2. We found that B-CLL cells could be induced to DNA
      synthesis upon treatment with IL-15 + Trx. The presence of Trx was essential for
      the IL-15-induced DNA synthesis. This contrasts to the effect of IL-15 + Trx on
      normal CD5+ and CD5- B cells, where IL-15 + Trx alone only induced limited DNA
      synthesis. IL-15 was as effective in the induction of DNA synthesis in B-CLL
      cells as IL-2, but about 100-fold less potent with an EC50 of 200 ng/ml. In
      addition we found that the IL-15 + Trx-induced proliferation was inhibited by
      CD40 stimulation. We conclude that IL-15 together with a proper costimulus can
      induce B-CLL cells to proliferate in vitro.

PMID- 9264385
TI  - The human T-cell lymphotropic viruses types I/II are not involved in T
      prolymphocytic leukemia and large granular lymphocytic leukemia.
AB  - The possible involvement of the human T lymphotropic viruses type I and II (HTLV
      I and -II) in lymphoproliferative disorders of mature T cells other than adult T
      cell leukemia/lymphoma (ATLL) has been controversial. Most studies have focused
      primarily on the cutaneous T cell lymphomas. However, skin involvement is a
      frequent feature of T prolymphocytic leukemia (T-PLL) and antibodies against HTLV
      I and -II have been reported in individuals with large granular lymphocytic (LGL)
      leukemia. We examined 36 patients with T-PLL and 28 with LGL leukemia for
      evidence of HTLV-I and -II. Polymerase chain reaction (PCR) was performed on DNA
      from fresh peripheral blood mononuclear cells (PBMCs) and PBMCs after short-term
      culture (STC) using primers against all parts of the HTLV-I genome (LTR, gag,
      env, pol, tax/rex) and against HTLV-II pol and gag. Reverse transcriptase (RT)
      activity was measured on supernatants from STCs using a sensitive PCR-based
      technique. No HTLV-I or -II sequences were found by PCR nor RT activity detected
      in the 64 cases. Our findings do not provide evidence of HTLV-I or -II infection
      in T-PLL and LGL leukemia patients from an HTLV-I nonendemic area. Previous
      positive reports on these disorders may represent technical artefacts, detection
      of endogenous HTLV-like sequences or reflect patients from endemic areas and a
      variable etiology of T cell diseases.

PMID- 9264386
TI  - The prognostic significance of T cell receptor beta gene rearrangements and
      idiotype-reactive T cells in multiple myeloma.
AB  - Clonal T cell populations with idiotype specificity are present in the peripheral
      blood of a proportion of patients with multiple myeloma. We have identified the
      presence of both T cell subpopulations with a specificity for autologous
      immunoglobin fragments and T cell receptor beta gene rearrangements in peripheral
      blood samples of patients with myeloma. T cell receptor beta gene rearrangements
      were detected in 38 of 119 patient samples (32%) and were more common in
      progressive disease (70%), than at diagnosis (25%) or in stable disease (23%).
      The 38 patients who had T cell receptor beta gene rearrangements detected at any
      time had a better overall survival (median not yet achieved) than the patients
      who never had rearrangements detected (median 45 months, n = 49; chi2 = 6.2, P <
      0.01). All 12 patients with T cell receptor beta gene rearrangements at diagnosis
      are still alive whereas the median survival for 28 patients with a germline
      configuration at diagnosis was 40 months (chi2 = 5.8, P > 0.01). The presence of
      T cell receptor beta gene rearrangements even conferred a survival advantage
      during progressive disease (median survival 44 months vs 19 months; chi2 = 8.7, P
      < 0.003). Two colour flow cytometry with biotinylated autologous immunoglobulin
      fragments demonstrated idiotype-reactive T cells in the peripheral blood of five
      out of 15 patients all of whom had T cell gene rearrangements. The remaining 10
      patients had neither idiotype-reactive T cells nor a detectable T cell receptor
      beta gene rearrangement in concurrent samples. Thus in patients with myeloma
      there was a good correlation between the presence of T cell receptor beta gene
      rearrangements and idiotype-reactive T cells. Patients with a rearranged T cell
      receptor beta gene had a significantly better prognosis.

PMID- 9264387
TI  - POEMS syndrome: report on six patients with unusual clinical signs, elevated
      levels of cytokines, macrophage involvement and chromosomal aberrations of bone
      marrow plasma cells.
AB  - POEMS syndrome is a multisystemic disorder characterized by the association of
      polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes and various
      other systemic clinical signs. The pathophysiology of this syndrome remains
      largely unknown. In order to gain insight into its pathophysiology, we studied
      the clinical characteristics and performed serum analysis (auto-antibodies,
      cytokine levels) and phenotypic and cytogenetic studies of bone marrow plasma
      cells (BMPC) in six patients with unequivocal POEMS syndrome. Two unusual
      clinical signs were present in these patients: pulmonary hypertension (two
      patients) and diffuse cutaneous necrosis (one patient). No auto-antibodies
      against peripheral nerve (PN) antigens (SGPG and SGLPG glycolipids, GM1, GD1a,
      GD1b and GT1b gangliosides) were found. Sequential evaluations of serum cytokines
      (IL-1-beta, IL-6 and TNF-alpha) showed a moderate to marked elevations of IL-6
      and TNF-alpha in all patients (up to six-fold for TNF-alpha and 16-fold for IL
      6). Using in situ hybridization of these cytokines mRNAs on lymph node specimens
      of two patients who had an angiofollicular lymph node hyperplasia, a strong
      positivity was found with the IL-1-beta antisense probe in lymph node
      macrophages. On skin biopsy a high number of cells expressing TNF-alpha mRNA was
      observed in the dermis. The biological features of BMPC: phenotype (expression of
      CD19 and CD56 antigens), kinetics (Ki-67 index), karyotype, DNA content and
      chromosomal in situ hybridization remained those of BMPC found in monoclonal
      gammopathy of undetermined significance. We conclude that POEMS syndrome is a
      hypercytokinemic syndrome in which BMPC are not of malignant type. Macrophages
      are involved in this syndrome and their role has to be further investigated as
      well as treatments which act through an anti-cytokine mechanism.

PMID- 9264388
TI  - Concomitant manifestation of systemic lupus erythematosus and low-grade non
      Hodgkin's lymphoma.
AB  - We describe a patient presenting with systemic lupus erythematosus (SLE) and
      concomitant low-grade (Ig) non-Hodgkin's lymphoma of the B cell type (B-NHL).
      Although the association of autoimmune disorder and lymphoma is well conceived,
      there is only scarce information available as to the simultaneous occurrence of
      both disease conditions in one patient. As in this patient diagnosis of Ig B-NHL
      was also based on the detection of a monoclonal population of CD5+ B lymphocytes,
      and given that the polyclonal expansion of CD5+ B cells has been previously
      reported in rheumatoid arthritis (RA), Sjogren's syndrome (SS) and single cases
      of SLE, the observations we made in this patient led us to discuss the role of
      the CD5+ population in the development of rheumatic disorders and concomitant
      lymphoid malignancy. Moreover, since impaired production rates of interleukin 3
      (IL-3) and interleukin 4 (IL-4) have been associated with an abnormal expansion
      of CD5, lymphoma cells and seeing that soluble interleukin 2 receptor (sIL-2R)
      serum levels were found to be positively correlated with disease activity both in
      SLE and Ig B-NHL, these parameters were investigated and related to the patient's
      disease state throughout the entire clinical observation period.

PMID- 9264389
TI  - Increased cystine uptake capability associated with malignant progression of Nb2
      lymphoma cells.
AB  - Analysis of rat, pre-T cell 'Nb2 lymphoma' sublines, manifesting different
      degrees of malignant progression, can indicate phenotypic changes potentially
      useful as therapeutic targets. In this study, the prolactin (cytokine)-dependent
      Nb2-11 and autonomous Nb2-SFJCD1 sublines were compared for in vitro thiol growth
      requirements. Whereas Nb2-11 culture growth depended on 2-mercaptoethanol (2-ME;
      33-100 microM), Nb2-SFJCD1 cells were 2-ME-independent. This difference stemmed
      from differential uptake of exogenous L-cystine, critically required for
      proliferation. Uptake of 35S-L-cystine (10 microCi/ml; 40 microM) showed Nb2-11
      cells had low cystine uptake capability; 2-ME enhanced cystine uptake to growth
      sustaining levels. Nb2-SFJCD1 cells did not require 2-ME due to intrinsic, 11
      fold higher cystine uptake via the x(c)- cystine/glutamate transport system. In
      absence of 2-ME, monosodium glutamate abrogated Nb2-SFJCD1 proliferation by
      specifically inhibiting cystine uptake (85% at 10 mM). Elevated glutathione (GSH)
      levels were not essential for growth of either line as shown with L-buthionine
      (S,R)-sulfoximine (0.1-4 mM) treatment. The cyst(e)ine requirement therefore did
      not primarily involve maintenance of normal GSH levels, reported critical for T
      lymphocyte replication. These and other results suggest increased cystine uptake
      capability constitutes another potential step in progression of T cell cancers
      which is not coupled to cytokine autonomy or metastatic ability development. The
      x(c)- transport system apparently provides a novel target for T cell cancer
      therapy. Its inhibition would suppress cystine uptake by certain progressed
      cells, and also interfere with cystine uptake, and subsequent cysteine release,
      by eg macrophages, thought to have a role in cysteine delivery to lymphoid cells.

PMID- 9264390
TI  - Diminished TCR signaling in cutaneous T cell lymphoma is associated with
      decreased activities of Zap70, Syk and membrane-associated Csk.
AB  - Malignant cells of patients with cutaneous T cell lymphoma (CTCL) are of
      monoclonal origin and of the CD4+/CD45RO+ subset. Since unlike their normal
      counterparts, triggering of their TCR/CD3 in vitro elicits only a weak mitogenic
      response, we set out to determine which of the signal transduction molecules
      initiated by anti-CD3E antibodies are affected in neoplastic cells. The results
      obtained from analysis of tumor cells from four patients show a general reduction
      in basal and induced tyrosine phosphorylation of a wide range of signaling
      proteins. Furthermore, the function of members from distinct families of protein
      tyrosine kinases was altered in neoplastic cells. The enzymatic activity of the
      membrane-bound fraction of Csk was suppressed, and its association with other
      cellular proteins was altered. There was a decline in the amount and activity of
      Syk, and a slight decrease in the specific activity of Lck kinases. Zap70 tyrosyl
      phosphorylation was reduced or undetectable and the kinase associated weakly, or
      not at all, with the TCR zeta chain. We propose that dampened TCR-triggered
      responses in CTCL are caused by suppression of an array of effector molecules
      required for coupling cell surface receptors to early and late signaling events.

PMID- 9264392
TI  - A new breakpoint, telomeric to TEL/ETV6, on the short arm of chromosome 12 in T
      cell acute lymphoblastic leukemia.
AB  - Abnormalities of the short arm of chromosome 12 frequently involve the TEL/ETV6
      gene in acute leukemias. In two cases of T cell acute lymphoblastic leukemia with
      translocation t(12;14)(p13;q11) and t(7;12)(q35;p13), respectively, the
      breakpoints were located telomeric to the TEL/ETV6 locus. Further fluorescence in
      situ hybridization (FISH) studies showed that the breakpoint was located between
      two markers, FGF6 (centromeric) and D12S983 (telomeric) on 12p in both patients.
      This result suggests that a new chromosomal breakpoint can nonrandomly involve
      rearrangements in T cell malignancies. The breakpoint on chromosome 14 was
      localized centromeric to the TRCA/D locus.

PMID- 9264391
TI  - The genetics of familial leukemia.
AB  - Familial leukemia is rare, but, as is the case with other cancer family
      syndromes, its study is likely to lead to the identification of genes causative
      of the far more common, sporadic cases. I review the clinical and, what is known
      of the molecular genetic features of familial leukemia. I propose a nosology
      based on whether the leukemia is a component of a medical syndrome or exists as a
      solitary disease, the apparent mode of inheritance, and the distribution of
      leukemia types and subtypes in affected family members. I review the recent
      findings from my group that leukemia is inherited with 'anticipation', in the
      form of a declining age of onset with each passing generation. I consider two
      models of leukemia genesis that can potentially account for anticipation in
      familial cases and incorporate epidemiological observations made in sporadic
      cases. The first model is analogous to trinucleotide repeat expansion in
      Huntington disease, myotonic dystrophy, and other inherited neurodegenerative
      illness demonstrating anticipation. The second model considers evidence that
      anticipation may be common to multiple types of familial cancer and is based on
      the intergenerational inheritance of multiple downstream mutations resulting from
      a defect in a single DNA repair gene.

PMID- 9264393
TI  - Germline configuration of nfkb2, c-rel and bcl3 in childhood acute lymphoblastic
      leukemia (ALL).
AB  - The well-known family of NF-kappaB/Rel transcription factors is a central
      regulator of growth, differentiation and apoptosis in hematopoietic cell
      lineages. There is increasing evidence for their role in malignant
      transformation, especially in lymphomas. To study the possible involvement of NF
      kappaB/Rel genes in the development of pediatric acute lymphoblastic leukemia
      (ALL), DNA samples from 140 patients were examined by Southern blot analysis. All
      samples revealed germline configuration of nfkb2, c-rel, and bcl3, indicating
      that structural alterations of these members of the NF-kappaB/Rel family are
      extremely rare, if existing at all in childhood ALL.

PMID- 9264394
TI  - Isochromosome 7q: the primary cytogenetic abnormality in hepatosplenic gammadelta
      T cell lymphoma.
AB  - Malignant lymphomas often have complex, nonrandom chromosomal abnormalities.
      Hepatosplenic gammadelta T cell lymphoma (gammadelta TCL) is an unusual post
      thymic T cell lymphoma that primarily involves liver and spleen, often in young
      adult males. Few cases have had cytogenetic analysis. We report a consistent
      isochromosome 7q [i(7q)] abnormality in three cases of hepatosplenic gammadelta
      TCL, one with i(7q) as the sole abnormality at presentation. Three patients, 15-,
      37- and 65-year-old males, presented with hepatosplenomegaly and fevers.
      Histopathologic, immunophenotypic, and molecular genetic studies supported the
      diagnosis. Spleen, liver, and bone marrow contained sinusoidal infiltrates of
      atypical lymphoid cells of T cell immunophenotype. PCR performed on two cases
      demonstrated clonal T cell receptor gamma gene rearrangements. Cytogenetic
      analysis of bone marrow showed i(7q) as the sole abnormality at presentation in
      one case. The second case showed i(7q) in addition to two normal chromosomes 7,
      and other structural and numerical abnormalities. The third case showed i(7q) and
      a deletion in the long arm of chromosome 11. These findings support the proposal
      that i(7q) represents the primary nonrandom cytogenetic abnormality in
      hepatosplenic gammadelta TCL, and plays a role in its pathogenesis.

PMID- 9264395
TI  - A family with chronic haemolysis and selective accumulation of erythrocyte CDP
      choline.
AB  - In this paper, we report a family with compensated chronic haemolysis where the
      only erythrocyte abnormality detected was an increased level of erythrocyte CDP
      choline. Using 31P-NMR spectroscopy and enzymatic analysis the possibility of a
      pyrimidine 5'-nucleotidase deficiency was excluded. Thus, this family represents
      the first evidence for a hereditary haemolytic anaemia where the inferred
      enzymatic defect is located to choline phosphotransferase, the enzyme catalysing
      the final step in lecithin synthesis. The family history indicates an autosomal
      dominant mode of transmission with incomplete penetrance.

PMID- 9264396
TI  - Transient hyperlipidemia during treatment of ALL with L-asparaginase is related
      to decreased lipoprotein lipase activity.
AB  - A 13-year-old girl with acute lymphoblastic leukemia (ALL) developed extremely
      high plasma triglyceride (TG) concentrations of 103 mmol/l (reference value <1.8
      mmol/l) during combination treatment with corticosteroids and asparaginase.
      Corticosteroids are known to induce the production of TG-rich particles. On the
      other hand, corticosteroids increase the activity of lipoprotein lipase (LPL), a
      key enzyme in the removal of TG from plasma. Generally, the increased LPL
      activity prevents an extreme rise in TG levels upon therapy with corticosteroids.
      In our patient, we found that the corticosteroid-induced LPL activity
      dramatically declined after therapy with L-asparaginase. This suggests that the
      extensive hypertriglyceridemia in our patient was due to an L-asparaginase
      induced decrease in LPL activity. This hypothesis was further supported by the
      finding that hypertriglyceridemia was less severe when corticosteroids and
      asparaginase were given separately.

PMID- 9264397
TI  - Clonal evolution to acute myeloblastic leukemia with MLL gene rearrangement from
      trisomy 8 clone.
AB  - A 20-year-old Japanese man was referred because of severe pancytopenia with 14%
      of abnormal blasts in hypocellular bone marrow. After treatment by granulocyte
      colony-stimulating factor (G-CSF) and transfusions of red blood cells,
      spontaneous remission was subsequently achieved. After 3 months' remission,
      however, the patient developed AML characterized by the abnormal karyotype:
      46XY,+8,t(9;11)(p22;q23). FISH study revealed the presence of trisomy 8 clone
      also in the hypoplastic state. While MLL-AF9 chimeric mRNA was observed in
      leukemic cells, it was not detectable in bone marrow cells from the hypoplastic
      state by RT-PCR. This is the first report of a trisomy 8 clone which evolved into
      one with a MLL gene rearrangement.

PMID- 9264398
TI  - Sezary cell-like leukemia with atypical immunophenotype.
AB  - We describe the clinical and laboratory features of an unusual case with Sezary
      cell-like leukemia. Clinical manifestations were: anemia (Hb 9.4 g/dl), severe
      thrombocytopenia (5 x 10(9)/l), lymphocytosis (43 x 10(9)/l) and splenomegaly.
      There was no lymphadenopathy, hepatomegaly or skin lesions. Bone marrow trephine
      showed diffuse infiltration by atypical lymphoid cells. By ultrastructural
      analysis the cells were small to medium-size lymphocytes with nuclear features
      identical to Sezary cells. Immunophenotyping showed that most peripheral blood
      mononuclear cells were negative with B lymphoid, myeloid, and stem cell
      associated markers and were also negative with most T lymphoid markers (CD2, CD4,
      membrane/cytoplasmic CD3, CD5 and CD8). However, they were positive with CD38
      (70%), CD7 (25%) and TIA-2 (25%). Molecular analysis showed a clonal
      rearrangement of the TCR beta and gamma chain genes. The patient was initially
      treated with vincristine, doxorubicin and asparaginase and then with six cycles
      of CHOP, achieving a complete remission and remaining free of disease 22 months
      from diagnosis. Aberrant immunophenotypes are not frequent in primary T cell
      leukemias. This is the first case of a rare type of T cell neoplasm, Sezary cell
      like leukemia, in which cells lacked most of the T cell-associated antigens.

PMID- 9264399
TI  - 2-Chlorodeoxyadenosine therapy for idiopathic hypereosinophilic syndrome.
AB  - Idiopathic hypereosinophilic syndrome (HES) is a rare disease with no established
      effective therapy. It has been reported that interleukin-5 (IL-5) produced by
      helper T cells plays a major role in the proliferation of eosinophils. The
      nucleotide analogue 2-chlorodeoxyadenosine (2-CdA), which induces excellent
      clinical responses in hairy cell leukemia, is known to suppress helper T cells;
      therefore, we used 2-CdA, alone or in combination with cytarabine, to treat
      patients with idiopathic HES. 2-CdA alone and combined with cytarabine resulted
      in a rapid and sustained decrease in circulating eosinophils in two patients with
      idiopathic HES that was refractory to steroids, hydroxyurea and cytarabine. The
      efficacy of 2-CdA alone and combined with cytarabine exceeded by far that of
      cytarabine alone. However, reverse transcription-polymerase chain reaction (RT
      PCR) did not show production of IL-5 or granulocyte-macrophage colony-stimulating
      factor mRNA in T cells as previously reported, and multiple cytokine receptors
      were found on eosinophils in idiopathic HES, suggesting that IL-5 may not be the
      sole cytokine involved in the regulation of idiopathic HES. The clinical efficacy
      of 2-CdA in idiopathic HES needs to be established on a large group of patients.

PMID- 9264400
TI  - Mutation of CDKN2 is infrequently detected in myelodysplastic syndrome.

PMID- 9264401
TI  - Intrathecal chemotherapy and bone marrow.

PMID- 9264402
TI  - Raf/MAPK and rapamycin-sensitive pathways mediate the anti-apoptotic function of
      p21Ras in IL-3-dependent hematopoietic cells.
AB  - The Ras signal transduction pathway is activated by a number of hematopoietic
      cytokines and is implicated in the prevention of apoptotic death in hematopoietic
      cells. Recent studies have provided evidence that the downstream of Ras is highly
      divergent and several independent pathways appear to mediate distinct biological
      functions of Ras. In the present study, we investigated the downstream pathway(s)
      of Ras responsible for the maintenance of hematopoietic cell survival by using
      various mutants of signaling molecules. Activation of the Raf/MAPK pathway in
      interleukin (IL) 3-dependent cells by expression of an oncogenic Raf or a Ras
      mutant (G12V/T35S) prevented apoptosis following IL-3 deprivation. In contrast,
      another Ras mutant (G12V/V45E), which is apparently incapable of activating MAPK,
      efficiently blocked apoptosis as well. It is therefore likely that the activation
      of the Raf/MAPK pathway is not an absolute requirement for the prevention of
      apoptosis, and there appears to be a Raf/MAPK-independent pathway that
      contributes to hematopoietic cell survival. Since Ras(G12V/V45E) was able to
      cause the phosphorylation of p70/S6 kinase, we inhibited the S6 kinase pathway by
      rapamycin and by wortmannin, and found that the anti-apoptotic function of
      Ras(G12V/V45E), but not of Ras(G12V), was critically influenced by both
      inhibitors. These results indicate that the Raf/MAPK and a rapamycin/wortmannin
      sensitive pathways mediate Ras function to prevent apoptotic death in
      hematopoietic cells.

PMID- 9264403
TI  - Induction of p27Kip1 degradation and anchorage independence by Ras through the
      MAP kinase signaling pathway.
AB  - While most untransformed cells require substrate attachment for growth (anchorage
      dependence), the oncogenic transformed cells lack this requirement (anchorage
      independence) and are often tumorigenic. However, the mechanism of loss of
      anchorage dependence is not fully understood. When rat normal fibroblasts were
      cultured in suspension without substrate attachment, the cell cycle arrested in
      G1 phase and the cyclin-dependent kinase inhibitor p27Kip1 protein and its mRNA
      accumulated. Conditional expression of oncogenic Ras induced the G1-S transition
      of the cell cycle and significantly shortened the half-life of p27Kip1 protein
      without altering its mRNA level. Inhibition of the activation of mitogen
      activated protein (MAP) kinase by cyclic AMP-elevating agents and a MEK inhibitor
      prevented the oncogenic Ras-induced degradation of p27Kip1. These results suggest
      that the loss of substrate attachment induces the cell cycle arrest through the
      up-regulation of p27Kip1 mRNA, but the oncogenic Ras confers anchorage
      independence by accelerating p27Kip1 degradation through the activation of the
      MAP kinase signaling pathway. Furthermore, we have found that p27Kip1 is
      phosphorylated by MAP kinase in vitro and the phosphorylated p27Kip1 cannot bind
      to and inhibit cdk2.

PMID- 9264404
TI  - c-Myc plays a role in cellular susceptibility to death receptor-mediated and
      chemotherapy-induced apoptosis in human monocytic leukemia U937 cells.
AB  - Human monocytic leukemia U937 cells readily undergo apoptosis when they are
      treated with TNF-alpha, anti-Fas antibody and anticancer drugs such as etoposide
      and Ara-C. To study the mechanism of apoptosis, we developed a novel apoptosis
      resistant variant, UC, from U937 cells. The UC cells showed resistance to
      apoptosis induced by TNF-alpha, anti-Fas antibody, etoposide and Ara-C. Somatic
      cell hybridization between U937 and UC showed that apoptosis-resistance to TNF
      alpha in UC was genetically recessive and resistance to etoposide was dominant,
      suggesting that UC has at least two different mutations functionally involved in
      apoptosis. Mechanistic analysis revealed that UC cells expressed reduced amounts
      of c-Myc. Transfection of the c-myc gene into UC cells restored the sensitivity
      of the cells to undergo apoptosis induced by TNF-alpha and anti-Fas, which
      attributes apoptosis-resistance in this circumstance to the reduced expression of
      c-Myc. On the other hand, c-myc transfection into UC cells could not restore
      their sensitivity to etoposide- and Ara-C-induced apoptosis, arguing against the
      role of c-myc in chemotherapy-induced apoptosis. However, treating the parental
      U937 cells with antisense oligonucleotides designed to reduce c-Myc expression
      rendered the cells resistant to etoposide-induced as well as to TNF-alpha-induced
      apoptosis. These results indicate that the reduced expression of c-Myc in UC is
      strongly associated with the resistance to etoposide-induced apoptosis. Our
      finding that c-myc transfection into UC could not restore the sensitivity to
      etoposide-induced apoptosis, suggests UC could have a second mutation that
      confers resistance to etoposide-induced apoptosis in a genetically dominant
      manner. Taken together, our present results indicate that c-Myc plays a role in
      cellular susceptibility to death receptor-mediated and chemotherapy-induced
      apoptosis.

PMID- 9264405
TI  - Activation of c-Myc uncouples DNA replication from activation of G1-cyclin
      dependent kinases.
AB  - Proto-oncogenes like c-myc are thought to control exit from the cell cycle rather
      than progression through the cell cycle itself. We now present a different view
      of Myc function. Exponentially growing Rat1-MycER fibroblasts were size
      fractionated by centrifugal elutriation. In these cells, activation of cyclin E-
      and cyclin A-dependent kinases, degradation of p27, hyperphosphorylation of
      retinoblastoma protein and activation of E2F occur sequentially at specific cell
      sizes. Upon activation of Myc, however, these transitions all occur
      simultaneously in small cells immediately after exit from mitosis. In contrast,
      Myc has no discernible effect on the cell size at which DNA replication is
      initiated. These data show first that Myc controls the activity of G1 cyclin
      dependent kinases independently from the transition between quiescence and
      proliferation and from any effect on cell growth in size. These data also provide
      evidence of at least one dominant mechanism besides activation of E2F and of
      cyclin E/cdk2 kinase, which prevents DNA replication unless a critical cell size
      has been reached.

PMID- 9264406
TI  - Characterization of an E2F-p130 complex formed during growth arrest.
AB  - Electrophoretic mobility shift assays were used to analyse the pattern of E2F
      transcription factor complexes containing pRB and related 'pocket' proteins
      associated with changes in growth of monkey CV-1 cells. Little change was noted
      in pRB/E2F complexes following growth arrest or serum stimulation. Serum
      starvation induced the formation of a novel slowly-migrating p130/E2F complex,
      termed C7, which was comparable to one reported previously in terminally
      differentiated C2C12 mouse cells (Corbeil et al., 1995, Oncogene 11, 909-920) and
      thought to contain one or more additional unidentified proteins. After serum
      stimulation, C7 complex disappeared in S-phase but returned during mitosis. A
      major E2F complex containing p107 appeared during S-phase but was undetectable at
      other times. It appeared likely that regulation of pRB, p107 and p130 occurs by
      several mechanisms. First, phosphorylation has previously been proposed to be
      involved. All pRB-related proteins were found to be highly phosphorylated during
      S-phase when E2F activity was highest, and hypophosphorylated in arrested cells
      when E2F activity was low. Second, the absolute levels of some members of the RB
      family varied during the cell cycle. Levels of pRB protein and pRB/E2F complexes
      changed little; however, the amounts of both p107/E2F and p130/E2F complexes
      varied according to the overall levels of p107 and p130 proteins. Formation of
      the novel C7 complex in serum arrested cells suggested a third regulatory
      mechanism mediated by interactions with additional proteins. Our studies
      indicated that binding of such proteins with p130/E2F occurred via a site in the
      'pocket' similar to that utilized by adenovirus E1A proteins. Such proteins could
      function as additional regulators of E2F-driven transcription.

PMID- 9264407
TI  - Sp1 recognition sites in the proximal promoter of the human vascular endothelial
      growth factor gene are essential for platelet-derived growth factor-induced gene
      expression.
AB  - Stimulation of NIH3T3 cells with platelet-derived growth factor (PDGF)-BB
      enhances expression of vascular endothelial growth factor (VEGF), an endothelial
      cell-specific mitogen and a key mediator of tumor angiogenesis. Here, we
      identified cis-acting VEGF promoter elements and trans-acting factors which are
      involved in PDGF-stimulated VEGF expression. By 5'-deletion and transient
      transfection analysis, a G + C-rich region at -85 to -50 of the human VEGF
      promoter was shown to be necessary and sufficient for both PDGF inducible and
      basal expression. The region contains three potential recognition sites for Sp1
      transcription factors, which overlap with two Egr-1 sites. Mutations that abolish
      the ability of Sp1 to interact with the VEGF promoter element also abrogate
      expression induced by PDGF. Mutations of the potential Egr-1 binding sites did
      not affect PDGF responsiveness. Gel shift and antibody supershift analyses showed
      that Sp1 and Sp3 interact constitutively with the VEGF promoter element. Our data
      strongly suggest that enhanced VEGF gene expression in PDGF-induced NIH3T3 cells
      is mediated by Sp1 and/or Sp3 transcription factors bound to the -85 to -50
      promoter region of the VEGF gene.

PMID- 9264408
TI  - The protooncogene product, PEBP2beta/CBFbeta, is mainly located in the cytoplasm
      and has an affinity with cytoskeletal structures.
AB  - The Pebpb2/Cbfb gene encodes the non-DNA binding beta subunit of the
      heterodimeric transcription factor, PEBP2/CBF, and has been implicated in a
      subtype of human acute myeloid leukemia, as well as being indispensable for the
      development of definitive hematopoiesis in the murine fetal liver. By examining a
      subcellular localization of the PEBP2beta/CBFbeta protein in tissue culture
      cells, we could reveal an additional aspect of the protein other than to be a
      subunit of a transcription factor. Immunoblot and immunocytochemical staining
      showed that PEBP2beta/CBFbeta was mostly present in the cytoplasm. This
      PEBP2beta/CBFbeta was free from its DNA-binding partner, the alpha subunit of
      PEBP2/CBF, as judged by the electrophoretic mobility shift assays. Furthermore, a
      significant amount of PEBP2beta/CBFbeta was retained in the cytoskeleton
      preparation after detergent extraction of the cells and was found by double
      immunofluorescence to colocalize with the F-actin on stress fibers and the
      vinculin in membrane processes. Thus, the present study extends PEBP2beta/CBFbeta
      to be a cytoskeleton-affinitive as well as nuclear protein. The implications of
      these results are discussed.

PMID- 9264409
TI  - Loss of p21CIP1/WAF1 does not recapitulate accelerated malignant conversion
      caused by p53 loss in experimental skin carcinogenesis.
AB  - The p21(CIP1/WAF1) protein is considered a downstream effector of tumor
      suppression by p53. We have previously demonstrated that p53 null keratinocytes
      have lower basal p21(CIP1/WAF1) mRNA levels and that tumors derived from these
      cells following transduction with the v-ras(Ha) oncogene grow faster than
      wildtype keratinocytes and rapidly progress to undifferentiated carcinomas
      (Cancer Res 54: 5584-5592, 1994). In this study, primary keratinocytes differing
      in p21(CIP1/WAF1) gene dose were transduced with v-ras(Ha) encoding retrovirus
      and grafted to nude mouse hosts to test whether the p53 null phenotype is
      mediated through p21(CIP1/WAF1). Resulting tumors from all genotypes were well
      differentiated papillomas; focal carcinomas were observed in 43, 30 and 44% of
      papillomas derived from +/+, +/- and -/- keratinocytes, respectively.
      p21(CIP1/WAF1) deficient keratinocytes expressing v-ras(Ha) do not display the
      degree of increased growth observed in p53 deficient tumors in vivo or the
      decreased responsiveness to negative growth regulation by Ca2+ in vitro. These
      results suggest that p21(CIP1/WAF1) does not regulate the differentiated
      phenotype or malignant progression of v-ras(Ha) initiated keratinocytes and that
      additional functions of the p53 protein other than transcriptional regulation of
      the p21(CIP1/WAF1) gene are required for p53 mediated tumor suppression.

PMID- 9264410
TI  - Mouse Neogenin, a DCC-like molecule, has four splice variants and is expressed
      widely in the adult mouse and during embryogenesis.
AB  - Neogenin is a member of the N-CAM family of cell adhesion molecules and is
      closely related to the DCC tumor suppressor gene product. Recently, it has been
      demonstrated that the DCC/Neogenin subfamily plays a key role in axonal guidance
      within the embryonic nervous system, however little is known about the function
      of DCC or Neogenin in non-neuronal tissues in vertebrates. To gain an
      understanding of Neogenin function outside of the nervous system we have cloned
      and sequenced the mouse homologue of Neogenin. We describe three alternatively
      spliced exons within the extracellular domain of Neogenin and a fourth
      alternatively spliced exon within the cytoplasmic domain. We further demonstrate
      that three of these alternatively spliced exons are developmentally regulated.
      Analysis of Neogenin mRNA expression showed that two distinct Neogenin
      transcripts are expressed at significant levels in a broad spectrum of adult
      mouse tissues and throughout the mid to late stages of embryogenesis. In situ
      hybridization studies on day 15.5 mouse embryos revealed that Neogenin is
      expressed widely throughout the developing mouse embryo, in both neuronal and non
      neuronal tissues. These observations suggests that Neogenin may play an integral
      role in regulating differentiation programmes and/or cell migration events within
      many embryonic and adult tissues.

PMID- 9264411
TI  - Mechanism of transformation by v-ErbA: substitution for steroid hormone receptor
      function in self renewal induction.
AB  - V-ErbA, a mutated thyroid hormone receptor (TR) alpha cooperates with tyrosine
      kinase oncoproteins to induce fatal erythroleukemia in chicks. In vitro, v-ErbA
      employs a similar cooperation to induce sustained proliferation and arrest
      differentiation of committed erythroid progenitors. V-ErbA has been proposed to
      function as a dominant-negative c-ErbA/TR alpha, since it lacks an AF-2
      transactivation domain and cannot be activated by hormone but retains the
      capacity to bind corepressors. However, v-ErbA fails to heterodimerize with the
      coreceptor RXR, exhibits an altered DNA binding specificity and fails to suppress
      the action of coexpressed TR alpha/c-ErbA in erythroblasts. In this paper, we
      identify a novel mechanism by which v-ErbA contributes to leukemogenesis.
      Recently, the glucocorticoid receptor (GR) was identified as a key regulator of
      proliferation and differentiation in normal erythroid progenitors. For this, the
      GR required to cooperate with endogenous receptor tyrosine kinases (c-Kit) and
      with the estrogen receptor (ER). Here, we demonstrate that v-ErbA can substitute
      for the ligand-activated GR and ER, inducing proliferation and arresting
      differentiation in the presence of specific GR and ER antagonists. Like the GR, v
      ErbA required to cooperate with c-Kit for both proliferation induction and
      differentiation arrest, being devoid of biological activity in the absence of an
      active c-Kit. In self-renewing erythroblasts, v-ErbA not only repressed known v
      ErbA target genes but also maintained high expression of c-myb. These biological
      activities of v-ErbA depended on distinct mutations in the DNA-binding domain.
      Additionally, v-ErbA acted as a partial, weak repressor of c-ErbA/TR alpha
      function in normal erythroblasts. It could be converted into a truly dominant
      negative receptor by restoring its ability to heterodimerize with RXR.

PMID- 9264413
TI  - Cooperative transformation of NIH3T3 cells by G alpha12 and Rac1.
AB  - The heterotrimeric G-protein, G alpha12, together with the closely-related G
      alpha13, are members of the G12 class of alpha-subunits important in mediating
      the signaling from seven transmembrane domain-spanning receptors. Recent evidence
      implicating both G alpha12 and G alpha13 in the activation of signaling pathways
      involving members of the RHO gene family led us to examine the role of Rac1, RhoA
      and Cdc42Hs in the transforming properties of G alpha12. Asparagine 17 (Asn 17)
      dominant inhibitory mutants of Rac1, and to a lesser extent RhoA, block focus
      forming ability of the GTPase-deficient mutant of G alpha12 (G alpha12 Leu 229)
      in NIH3T3 cells. In turn, wild-type G alpha12 cooperates well with Rac1 Val 12
      but not with RhoA Leu 63 mutant in transforming NIH3T3 cells. Interestingly, the
      morphology of foci induced by G alpha12 and RhoA mutants are strikingly similar
      and is distinct from those displayed by Rac1 Val 12 mutant. The fact that G
      alpha12's ability to induce mitogenesis in NIH3T3 cells is not significantly
      perturbed by C3 ribosyltransferase suggested that RhoA does not play a major role
      in G alpha12-induced mitogenic events. Activated mutant of Rac1 has previously
      been demonstrated to stimulate the activity of the stress-induced c-Jun N
      terminal kinase/stress-activated protein kinases (JNK/SAPKs). Transient co
      transfection of Rac1 Val 12 mutant with the wild-type G alpha12 in COS7 cells
      leads to the further activation of an exogenously expressed hemagglutinin(HA)
      tagged JNK. Furthermore, the cooperation between G alpha12 and Rac1 in cellular
      transformation is correlated with their ability to stimulate transcription from c
      fos serum response element (SRE).

PMID- 9264412
TI  - Essential role of calcium in the regulation of MAP kinase phosphatase-1
      expression.
AB  - Mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1) is a dual
      specificity protein phosphatase encoded by an immediate-early gene responsive to
      growth factors and stress. The MKP-1 protein selectively inactivates MAP kinases
      in vitro by dephosphorylation of the regulatory Thr and Tyr residues. Little is
      known on the mechanisms that regulate MKP-1 gene expression. Here, we demonstrate
      that Ca2+ is both necessary and sufficient for the induction of MKP-1 gene
      expression. Treatment of Rat1 fibroblasts with the Ca2+ chelating agent BAPTA
      completely suppressed serum-induced MKP-1 expression in a dose- and time
      dependent manner. The inhibitory effect of BAPTA was observed at the level of the
      protein and the mRNA. Importantly, Ca2+ chelation blocked the induction of MKP-1
      expression in response to all stimuli tested and in different cell types.
      Increasing the intracellular concentration of Ca2+ with the ionophore A23187 was
      sufficient to induce MKP-1 mRNA and protein expression in rat fibroblasts. We
      also provide evidence that activation of MAP kinases is not an absolute
      requirement for induction of the MKP-1 gene. Exposure of rat fibroblasts to
      A23187 induced MKP-1 expression without activating the JNK and p38 MAP kinase
      pathways. Also, inhibition of the ERK pathway with the selective MEK inhibitor
      PD98059 did not interfere with serum-stimulated MKP-1 mRNA expression. These
      results will help define the regulatory mechanisms that govern MKP-1 gene
      transcription in target cells.

PMID- 9264415
TI  - Comparison of maximum versus submaximum exercise testing in providing prognostic
      information after acute myocardial infarction and/or coronary artery bypass
      grafting.
AB  - Exercise testing after acute myocardial infarction (AMI) provides prognostic
      information. In many studies submaximum exercise tests performed until a given
      work load, metabolic equivalents (METs) level, or heart rate were used or
      patients discontinued the exercise test prematurely because of symptoms. We
      showed recently that peak oxygen uptake during maximum exercise provides
      independent prognostic information in patients with coronary artery disease. It
      is, however, not known whether maximum exercise testing is superior in predicting
      mortality than testing until a target level. Second, it is unclear which target
      end point best classifies patients at increased risk. Therefore, the independent
      relation between mortality and indexes of, respectively, maximum and submaximum
      exercise capacity, were analyzed in 527 patients, who were tested until
      exhaustion. To express submaximum exercise capacity dichotomous variables (the
      ability to reach a target METs level or not), and a continuous variable relative
      to maximum exercise capacity (the ventilatory anaerobic threshold) were used.
      After adjustment for significant covariates, peak oxygen uptake was significantly
      related to all-cause and cardiovascular mortality. The target level of 5 METs and
      the ventilatory anaerobic threshold, when expressed in absolute workload, were
      related to mortality when unadjusted, but after adjustment for age and other
      confounders significancy was lost. In multiple Cox regression analysis, the
      prognostic power of peak oxygen uptake remained significant when 5 METs or the
      anaerobic threshold were forced into the equations. When analyzing the relation
      of various METs levels with mortality, the 7 METs level was independently related
      to all-cause and cardiovascular mortality and yielded the highest diagnostic
      accuracy. We conclude that maximum exercise testing is more potent in predicting
      mortality than the ability to reach a predetermined level of exercise, such as
      the commonly used 5 METs level or the anaerobic threshold. Otherwise, the use of
      a higher target level of 7 METs is recommended.

PMID- 9264414
TI  - Analysis of the DNA-binding activities of Myc/Max/Mad network complexes during
      induced differentiation of U-937 monoblasts and F9 teratocarcinoma cells.
AB  - The bHLHZip protein Max interacts with both the Myc and Mad family proteins
      forming heterodimers which specifically bind certain E-box DNA recognition
      sequences, thereby regulating transcription. Whereas Myc proteins actively
      promote cell proliferation, Mad complexes have the opposite function. Although
      the main regulation of this network seems to be the control of myc- and mad
      family gene expression, regulation at the level of DNA-binding and
      transactivation may also be in operation. Few studies on the DNA-binding activity
      of native Myc:Max or Max:Mad complexes have been reported mainly due to technical
      difficulties. To overcome these problems we have developed a specific and
      sensitive solid phase DNA-binding assay based on partial purification of native
      Myc, Max and Mad1 complexes by immunological methods. Using this technique we
      report that the DNA-binding activity of c-Myc-containing complexes is reduced
      during induced differentiation of U-937 monoblasts and F9 embryonic
      teratocarcinoma cells. In contrast, the DNA-binding of Mad1-containing complexes
      increases during monocytic differentiation. In general, the DNA-binding activity
      of c-Myc and Mad1 correlate with their expression. However, our studies of early
      kinetics of TPA-induced differentiation of U-937 cells as well as of late events
      during F9 differentiation suggest that post-translational regulation of Myc and
      Max DNA-binding may also occur. The solid phase DNA-binding assay may thus
      provide a tool to study the regulation of DNA-binding in more detail.

PMID- 9264416
TI  - Usefulness of the addition of heart rate variability to Holter monitoring in
      predicting in-hospital cardiac events in patients with unstable angina pectoris.
AB  - Transient ischemia on Holter monitoring is a major determinant of outcome in
      unstable angina. In this study we investigated whether analysis of heart rate
      variability (HRV) may further improve the prognostic yield of Holter monitoring
      in this clinical setting. We performed 24-hour Holter monitoring in 75 patients
      with unstable angina (59 men, aged 62 +/- 9 years) within 12 hours of hospital
      admission. Number and duration of myocardial ischemic episodes, and both time
      domain and frequency domain HRV measures were obtained from Holter recordings. In
      hospital major cardiac events (death or myocardial infarction) occurred in 7
      patients (9%). Episodes of ST-segment depression on Holter monitoring were found
      in 6 of 7 patients (86%) with and in 26 of 68 patients (38%) without events (p
      <0.05). There were no differences between patients with or without events in both
      time domain (standard deviation [SD] of all normal RR intervals in the entire 24
      hour electrocardiographic recording (SDNN), SD of the mean RR intervals for all 5
      minute segments (SDANN-i), mean of SD of all RR intervals for all 5-minute
      segments (SDNN-i), percentage of differences between adjacent RR intervals >50 ms
      (pNN50), and square root of the mean squared differences of successive RR
      intervals) (RMSSD), and frequency domain (ultra low, very low, low, and high
      frequency) HRV indexes. However, the low-frequency/high-frequency (LF/HF) ratio
      was significantly higher in patients with cardiac events (2.12 +/- 1.4 vs 1.48 +/
      0.5, p = 0.01). Moreover, when considering only the 32 patients with myocardial
      ischemic episodes on Holter monitoring, the LF/HF ratio was again higher in the 6
      patients with than the 26 patients without major cardiac events (2.45 +/- 1.5 vs
      1.31 +/- 0.3, p <0.01). Multivariate logistic regression, including clinical and
      angiographic variables, showed that transient ischemia on Holter monitoring was
      the only independent determinant of outcome (odds ratio = 12.2, p = 0.03), with
      the LF/HF ratio being only slightly over statistical significance (odds ratio for
      0.1 increments = 2.8, p = 0.08). Our data confirm that transient ischemia on
      Holter monitoring is a powerful predictor of cardiac events in unstable angina
      and indicates that an imbalance in cardiac autonomic tone toward a prevalence of
      sympathetic activity increases the risk of events in this group of patients.

PMID- 9264418
TI  - Cardiac sympathetic denervation in patients with coronary artery disease without
      previous myocardial infarction.
AB  - Myocardial infarction damages sympathetic nerve fibers coursing through the
      infarct zone. In this study we investigated whether coronary artery disease
      without myocardial infarction results in sympathetic denervation. We examined 12
      patients without a history of previous myocardial infarction and 19
      postinfarction patients. 1-123 metaiodobenzylguanidine (MIBG) and technetium-99m
      sestamibi (MIBI) single-photon emission tomography were conducted at rest to
      determine the extent of denervated myocardium and the extent of myocardium with
      reduced perfusion, respectively. In addition, myocardial perfusion during
      exercise was assessed with MIBI. A MIBG or MIBI defect was determined as being
      regional uptake of < or =30% of the maximal myocardial activity. All but 1
      patient without previous infarction had MIBG defects. MIBG defects (10.3 +/- 8.5%
      of left ventricular mass) were significantly larger than MIBI defects at rest
      (2.4 +/- 3.2%, p <0.001) and during exercise (4.8 +/- 6.1%, p <0.05). In
      multiregression analysis, the size of an MIBG defect was associated with severity
      of coronary stenoses (> or =90% of lumen diameter; p <0.05), but not with age,
      number of significant stenoses (> or =50% of lumen diameter), left main disease,
      functional class, left ventricular ejection fraction, angina pectoris, maximal ST
      depression, or mean workload during exercise test. MIBG and MIBI defects were
      significantly larger in patients with severe coronary stenoses than in patients
      with moderate stenoses (50% to 89% of lumen diameter) (16.4 +/- 8.9% vs 6.0 +/-
      5.2% [p <0.05] and 5.0 +/- 3.1% vs 0.6 +/- 1.3% [p <0.001], respectively). The
      size of MIBG (16.1 +/- 8.9%) and MIBI defects (7.3 +/- 6.5%) at rest in
      postinfarction patients did not differ from patients with severe stenoses. Our
      study demonstrates that cardiac adrenergic tissue is very sensitive to ischemia
      and that regional cardiac sympathetic denervation can occur in patients with
      stable coronary artery disease without previous myocardial infarction.

PMID- 9264417
TI  - Impact of acute propranolol administration on dobutamine-induced myocardial
      ischemia as evaluated by myocardial perfusion imaging and echocardiography.
AB  - Beta-blocker therapy may delay or completely prevent myocardial ischemia during
      exercise testing, as assessed by ST-segment shifts, myocardial perfusion defects,
      or echocardiographic wall motion abnormalities. However, the impact of beta
      blocker therapy on these end points during dobutamine stress testing has not been
      well established. The purpose of this study was to determine the impact of
      propranolol on dobutamine stress testing with ST-segment monitoring, technetium
      99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT)
      imaging, and echocardiography. In 17 patients with known reversible perfusion
      defects, dobutamine stress tests with and without propranolol were performed in
      randomized order and on separate days, following discontinuation of oral beta
      blockers and calcium antagonists. Propronolol was administered intravenously to a
      cumulative dose of 8 mg or to a maximum heart rate reduction of 25% and
      dobutamine was infused in graded doses in 3 minute stages until a standard
      clinical end point or the maximum dose of 40 microg/kg/min was achieved. The
      dobutamine stress test after propranolol was associated with a lower maximum
      heart rate (83 +/- 18 vs 125 +/- 17, p <0.001) and rate pressure product (14,169
      +/- 4,248 vs 19,894 +/- 3,985, p <0.001) despite a higher infusion dose. The
      SPECT myocardial ischemia score was also lower (6.9 +/- 5.8 vs 10.1 +/- 7.1, p =
      0.047) and fewer echocardiographic segments were abnormal (3.4 +/- 3.0 vs 4.6 +/-
      3.4, p = 0.042). In 4 of 17 patients, reversible perfusion defects and
      echocardiographic wall motion abnormalities were detected during the control but
      not during the propranolol test. Thus, during dobutamine stress testing, beta
      blocker therapy attenuates, and in some cases eliminates, evidence of myocardial
      ischemia.

PMID- 9264419
TI  - Effects of fluvastatin on coronary atherosclerosis in patients with mild to
      moderate cholesterol elevations (Lipoprotein and Coronary Atherosclerosis Study
      [LCAS]).
AB  - Despite the potential for reduced morbidity and mortality, aggressive
      intervention against mild to moderate hypercholesterolemia in patients with
      coronary heart disease (CHD) remains controversial and infrequently practiced.
      Eligible patients in the 2.5-year Lipoprotein and Coronary Atherosclerosis Study
      were men and women aged 35 to 75 years with angiographic CHD and mean low-density
      lipoprotein (LDL) cholesterol of 115 to 190 mg/dl despite diet. Patients (n =
      429; 19% women) were randomized to fluvastatin 20 mg twice daily or placebo. One
      fourth of patients were also assigned open-label adjunctive cholestyramine up to
      12 g/day because prerandomization LDL cholesterol remained > or = 160 mg/dl. The
      primary end point, assessed by quantitative coronary angiography, was within
      patient per-lesion change in minimum lumen diameter (MLD) of qualifying lesions.
      Across 2.5 years, mean LDL cholesterol was reduced by 23.9% in all fluvastatin
      patients (+/- cholestyramine) (146 to 111 mg/dl) and by 22.5% in the fluvastatin
      only subgroup (137 to 106 mg/dl). Primary end point analysis (340 patients)
      showed significantly less lesion progression in all fluvastatin versus all
      placebo patients, deltaMLD -0.028 versus -0.100 mm (p <0.01), and for fluvastatin
      alone versus placebo alone, deltaMLD -0.024 versus -0.094 mm (p <0.02). A
      consistent angiographic benefit with treatment was seen whether baseline LDL
      cholesterol was above or below 160 or 130 mg/dl. Beneficial trends with treatment
      were also consistently seen in clinical event rates but were not statistically
      significant. Thus, lipid lowering by fluvastatin in patients with mildly to
      moderately elevated LDL cholesterol significantly slowed CHD progression.

PMID- 9264420
TI  - Design & rationale of the Air Force/Texas Coronary Atherosclerosis Prevention
      Study (AFCAPS/TexCAPS).
AB  - The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) is
      a randomized, double-blind, placebo-controlled primary prevention trial. It is
      designed to test the hypothesis that in addition to a lipid-lowering diet,
      treatment with lovastatin is more effective than placebo in reducing acute major
      coronary events (i.e., sudden cardiac death, fatal and nonfatal myocardial
      infarction, and unstable angina) in a cohort with normal to mildly elevated total
      (180 to 264 mg/dl) and low-density lipoprotein (LDL) cholesterol (130 to 190
      mg/dl) and low high-density lipoprotein (HDL) cholesterol (< or =45 mg/dl for men
      and < or =47 mg/dl for women). Two sites in Texas, Lackland Air Force Base in San
      Antonio and the University of North Texas Health Science Center in Fort Worth,
      will conduct the study. After at least 12 weeks of an American Heart Association
      Step 1 diet and 2 weeks placebo run-in, 6,605 men and women, ages 45 to 73 and 55
      to 73 years, respectively, without clinical evidence of coronary heart disease,
      are randomized in equal numbers to either lovastatin (20 mg/day) or placebo.
      Study procedures maintain the blind, allowing titration of lovastatin from 20 to
      40 mg/day to achieve an LDL cholesterol goal of < or = 110 mg/dl. All
      participants are followed until study completion, when 320 participants have had
      a primary end point or a minimum of 5 years after the last participant is
      randomized, whichever occurs last. All end points are adjudicated by an
      independent committee using prespecified criteria. Unique features of this trial
      are (1) the inclusion of unstable angina in the primary end point to reflect the
      increasing trend to treat coronary heart disease aggressively before a myocardial
      infarction has occurred, (2) aggressive pharmacologic intervention, with
      titration, to attain an LDL cholesterol goal less than the current National
      Cholesterol Education Panel guidelines for primary prevention, and (3) a cohort
      that includes women, the elderly, and those with mild to moderate hyperlipidemia
      and low HDL cholesterol. Compared with earlier studies, results will be
      applicable to a broader population and may help clarify the role of aggressive
      LDL cholesterol reduction measures in primary prevention. Treatment of this
      population is likely to realize the greatest cumulative long-term benefit in the
      prevention of acute major coronary events.

PMID- 9264421
TI  - Systolic and diastolic effects of variable atrioventricular delay in patients
      with complete heart block and normal ventricular function.
AB  - This study was designed to demonstrate the effects of varying the
      atrioventricular delay (AVD) on ventricular diastolic filling dynamics and the
      resultant stroke volume in patients with complete heart block and normal cardiac
      function. We studied 7 patients with normal cardiac function in whom a dual
      chamber pacemaker had been implanted because of complete heart block. Doppler and
      M-mode echocardiography was performed at 70, 100, 140, 180, and 220 ms, AVD with
      the device in DDD mode at a rate of 80 beats/min. The effects of these variable
      intervals on the contribution of the E and A waveform to the diastolic filling,
      on the stroke volume, and on the systolic intervals were evaluated. Optimization
      of this interval, with a 19% increase in stroke volume was achieved in the group
      of patients at an AVD of 140 ms. When considered individually, the AVD associated
      with the largest stroke volume, was 100 ms in 2 patients and 140 ms in the
      remaining 5. At this individual optimal AVD the ventricular septal contraction
      occurred 31 +/- 14 ms, before the end of the transmitral flow. The optimal AVD
      is, therefore, the one which synchronizes the ventricular and atrial systole so
      that the first ventricular septal contraction occurs after the peak of the A
      wave, just before the end of the transmitral flow. Because of the different
      functional cardiovascular status of the single patient, this parameter should be
      individualized; this can be clinically important as it may lead, in this patient
      population, to an improvement of the stroke volume up to 42%.

PMID- 9264423
TI  - Differing effects of age on heart rate variability in men and women.
AB  - Gender and age are both known to affect heart rate variability (HRV). Their
      interaction is not known. HRV, determined from 24-hour Holter recordings, was
      compared between gender-matched older (15 men and 15 women, aged 67 +/- 3 years,
      range 64 to 76) and younger (15 men and 15 women, aged 33 +/- 4 years, range 26
      to 42) subjects selected for an age difference of approximately 35 years. HRV for
      older and younger subjects was compared separately by gender. HRV was also
      compared by gender within groups. Heart rates were significantly higher, and all
      time and frequency domain indexes of HRV were significantly lower among the older
      than among the younger men. Among the women only the shorter term indexes of HRV
      were significantly lower in the older group. When HRV was compared by gender
      within age groups, there were no significant differences between men and women in
      the older group. In the younger group, men had lower heart rates, and all 24-hour
      time domain indexes of HRV, except those that reflect vagal modulation of heart
      rate, were significantly higher than those in women. We conclude that HRV is
      comparable in older men and women. However, HRV is differently affected by age.
      In men, for whom initial levels of HRV are significantly higher, older age is
      associated with a global reduction in HRV, reflecting reductions in both
      sympathetic and parasympathetic modulation and a loss of circadian variability.
      In women, older age is associated mainly with a decline in shorter term indexes
      of HRV without significant changes in circadian variability.

PMID- 9264422
TI  - Clinical and socioeconomic profile of patients with malignant ventricular
      arrhythmias in 1993 to 1995. AVID investigators. Antiarrhythmics Versus
      Implantable Defibrillator.
AB  - This report summarizes the clinical and socioeconomic characteristics of the
      first 542 patients entered into the Antiarrhythmics Versus Implantable
      Defibrillator (AVID) trial. AVID is a multicenter trial comparing a strategy of
      initial implantable cardioverter-defibrillator placement to initial
      antiarrhythmic drug therapy in preventing death in patients resuscitated from
      cardiac arrest who were not taking amiodarone and who did not have an implantable
      cardioverter-defibrillator in place at the time of the index event. These
      patients were randomly assigned to immediate defibrillator placement or to "best"
      medical therapy. Clinical and socioeconomic histories were collected by interview
      using standard terms developed for the study. Patients without (group 1) and with
      (group 2) a history of prior cardiac arrest were compared. The mean age of the
      542 patients was 65 +/- 10 years, most were men, white, had coronary disease, and
      were highly functional despite the fact that only a minority were employed.
      Almost all had some form of health insurance. At the time of the index event, few
      were taking any therapy to prevent cardiac arrest, even in the group of patients
      with a history of previous cardiac arrest. Thus, the clinical and socioeconomic
      profile of patients resuscitated from sudden cardiac death entered into the AVID
      study is generally as expected. There is a striking absence of any attempt at
      chronic therapy to prevent cardiac arrest in most patients with a prior
      ventricular tachycardia or ventricular fibrillation.

PMID- 9264424
TI  - Doppler echocardiographic assessment of progression of aortic regurgitation.
AB  - The rate of progression of the degree of chronic aortic regurgitation (AR) is
      unknown. Furthermore, although left ventricular (LV) dilation has been studied in
      patients with severe AR, its rate and determining factors, and specifically, its
      relation to the degree of regurgitation remain to be established and have not
      previously been studied for mild and moderate AR. The purpose of this study was
      to explore the progression of chronic AR by 2-dimensional and Doppler
      echocardiography, and the relation of LV dilation to the fundamental regurgitant
      lesion and its progression in patients with a full spectrum of initial AR
      severity. We studied 127 patients with AR by 2-dimensional and Doppler
      echocardiography (69 men; 59 +/- 21 years; 67 with mild, 45 with moderate, 15
      with severe AR). AR increased in 38 patients (30%) (25% of mild, 44% of moderate,
      and 50% of moderate to severe lesions; p <0.006). The ratio of proximal AR jet
      height to LV outflow tract height also increased (30.3 +/- 17.5% vs 35.2 +/-
      19.7%; p <0.0001). Initial LV volumes and mass were larger in patients with more
      severe AR and increased significantly during follow-up (138 +/- 53 to 164 +/- 70
      ml; 59 +/- 32 to 71.7 +/- 42 ml; 203 +/- 89 to 241 +/- 114 g; p <0.0001). LV
      volumes and mass increased faster in patients with more severe AR, and in those
      in whom the degree of AR progressed more rapidly. Finally, patients with bicuspid
      aortic valve (n = 21) had a higher prevalence of severe AR than patients with
      tricuspid aortic valves (52% vs 4%; p <0.001). In conclusion, AR is a progressive
      disease not only in patients with severe AR but also in those with mild and
      moderate regurgitation. Patients with more severe AR have larger left ventricles
      that also dilate more rapidly.

PMID- 9264425
TI  - Role of right ventricular and pulmonary functional abnormalities in limiting
      exercise capacity in adults with congenital heart disease.
AB  - This study evaluates right ventricular (RV) and pulmonary function during
      exercise in adults with congenital heart disease (CHD). Thirty-one patients with
      CHD involving the right side of the heart underwent symptom-limited bicycle
      exercise testing with simultaneous expired gas analysis and measurement of RV
      ejection fraction (EF). Twenty-one age-matched normal controls underwent the
      identical exercise protocol. Maximal oxygen consumption was lower in the CHD than
      in normal controls (19.5 +/- 6.4 vs 30.5 +/- 0.8 ml/kg/min, p = 0.0001 patients
      vs controls). Both heart rate (156 +/- 25 vs 171 +/- 13 beats/min, p = 0.01) and
      oxygen pulse (9.3 +/- 3.7 vs 12.3 +/- 3.7 ml/beat, p = 0.01), an indirect measure
      of stroke volume, were found to be lower in the CHD group at peak exercise.
      Pulmonary dysfunction was evidenced in the CHD group by decreased forced
      expiratory volume, forced vital capacity and maximum voluntary ventilation, and
      by a higher ventilation/expired carbon dioxide ratio at peak exercise (37.2 +/-
      6.9 vs 33.0 +/- 5.4, p = 0.02), suggesting an increase in dead space ventilation.
      Maximal oxygen consumption was lower in patients whose RVEF decreased with
      exercise (17.6 +/- 5.4 vs 22.8 +/- 6.4 ml/kg/min, p = 0.03 "decrease RVEF" group
      vs "increase RVEF" group). Maximal oxygen consumption correlated with the change
      in RVEF only in the group whose RVEF decreased with exercise (r = 0.5, p = 0.03).
      In the group that had increased RVEF with exercise, maximal oxygen consumption
      correlated with forced expiratory volume (r = 0.7, p = 0.02). Thus, adults with
      CHD have a reduced functional capacity compared with normal controls. This
      phenomenon appears to be associated with both RV and pulmonary abnormalities.

PMID- 9264426
TI  - Development and validation of a noninvasive method to determine arterial pressure
      and vascular compliance.
AB  - The ability not only to record automated systolic and diastolic pressure, but
      also to derive measurements of the rate of pressure change during the cardiac
      cycle, would have great potential clinical value. A new method has been developed
      to obtain pressure measurements at 20-ms intervals by oscillometric cuff signal
      pattern recognition. Derivation of noninvasive pressure measurements is based on
      a T tube aorta and straight tube brachial artery, and assumes that the systolic
      phase of the suprasystolic cuff signal and the diastolic phase of the
      subdiastolic cuff signal most closely approximate systolic and diastolic aortic
      pressures, respectively. Arterial pressures obtained by this method were compared
      with simultaneous invasive measurements from the thoracic aorta in 36 patients.
      Good agreement was observed between noninvasive and invasive methods for systolic
      (146 +/- 4 vs 145 +/- 5 mm Hg), diastolic (80 +/- 2 vs 77 +/- 2 mm Hg), and mean
      (100 +/- 3 vs 100 +/- 3 mm Hg) arterial pressures, and correlation coefficients
      were r = 0.94, 0.91, and 0.95, respectively. To assess the validity of
      measurements of the rate of pressure change, oscillometric cuff signals from a
      subgroup of 14 patients were analyzed in detail for the peak positive pressure
      derivative (dP/dt(Max)), peak negative pressure derivative (dP/dt(Min)), and time
      interval between peak positive and peak negative pressure derivatives [t(pp)].
      Results (mean +/- SEM) were: [table in text]. The incorporation of measurements
      of the rate of pressure change into a physical model of the brachial artery was
      used to derive vascular compliance. A significant correlation was observed
      between vascular compliance derived from the oscillometric signal and
      determinations by either thermodilution or Fick methods and noninvasive pressures
      (n = 20, r = 0.83, p <0.001). Day-to-day variability for blood pressure and
      vascular compliance derived by the noninvasive method did not differ by >4%,
      representing a reproducible measure of vascular structure and function. We
      conclude that the measurement of absolute pressure and rate of pressure change
      show good correlation with catheter data and that vascular compliance can be
      reliably assessed by this new method. The technology should provide a valuable
      noninvasive tool for the assessment of both cardiac function and vascular
      properties.

PMID- 9264427
TI  - Effect of supplemental oral L-arginine on exercise capacity in patients with
      stable angina pectoris.
AB  - A randomized, double-blind, placebo-controlled study in patients with clinical
      symptoms of stable angina pectoris and healed myocardial infarction (n = 22) has
      shown that oral supplementation with L-arginine (6 g/day for 3 days) increases
      exercise capacity (tested on a Marquette case 12 treadmill according to the
      modified Bruce protocol). Results suggest that the inefficient L-arginine/nitric
      oxide system contributes to limitation of myocardial perfusion and/or peripheral
      vasodilation during maximum exercise in patients with stable angina pectoris.

PMID- 9264428
TI  - Distinction between open and occluded infarct-related arteries using contrast
      enhanced magnetic resonance imaging.
AB  - Ultrafast contrast-enhanced magnetic resonance imaging can be used to distinguish
      open and closed infarct-related arteries. An open artery is characterized by a
      faster rise and fall in signal intensity.

PMID- 9264429
TI  - Circadian variation in the onset of acute pulmonary edema and associated acute
      myocardial infarction in diabetic and nondiabetic patients.
AB  - It is known that most acute cardiovascular events exhibit a circadian rhythm in
      their onset. The authors describe differences in the circadian rhythm of onset of
      acute pulmonary edema and associated acute myocardial infarction in diabetic and
      nondiabetic patients.

PMID- 9264430
TI  - Cardiologists' perception of risk of coronary revascularization procedures.
AB  - We sought to determine if differences exist between interventional and
      noninterventional cardiologists in the perception of risk of revascularization
      procedures and to compare the physicians' estimates with a computer-based
      predictor formula from a large regional database. We found that interventional
      cardiologists perceived greater risk of percutaneous transluminal coronary
      angioplasty-related morbidity and mortality than noninterventionalists and that
      these differences were accentuated in female patients, the elderly, and the most
      seriously ill patients.

PMID- 9264431
TI  - Lack of arrhythmogenicity with ST-segment elevation during high-dose of
      dobutamine atropine stress in patients with documented or suspected coronary
      artery disease.
AB  - The angiographic, echocardiographic, and electrocardiographic correlates of ST
      segment elevation during high-dose dobutamine-atropine stress were prospectively
      looked at in a group of high-risk patients. Unlike exercise-induced ST elevation,
      ST-segment elevation with dobutamine-atropine stress, while indicating transmural
      ischemia, did not increase rate of arrhythmias and hence by itself may not be an
      indication to terminate the test.

PMID- 9264432
TI  - Blood pressure responses to mental stress in emotionally defensive patients with
      stable coronary artery disease.
AB  - Emotional defensiveness, defined by concealment of both negative emotions and
      personal vulnerability, was substantially and consistently correlated with the
      magnitude of blood pressure reactions to 2 types of mental stress among coronary
      patients, independently of clinical status. Given recent studies denoting stress
      related blood pressure surges as triggers of dangerous cardiovascular events,
      exaggerated vasomotor reactions among defensive patients may be of clinical
      significance.

PMID- 9264434
TI  - Changes in serum lipids when fluvastatin is substituted for lovastatin in the
      same doses.
AB  - This study evaluated changes in serum lipids when fluvastatin was substituted for
      lovastatin using equivalent doses. Results showed that serum lipids, especially
      low-density lipoprotein cholesterol, significantly increase with this
      substitution.

PMID- 9264433
TI  - Effectiveness of atorvastatin for reducing low-density lipoprotein cholesterol to
      National Cholesterol Education Program treatment goals.
AB  - Atorvastatin is a highly efficacious hydroxymethylglutaryl-coenzyme A reductase
      inhibitor that has been shown to reduce low-density lipoprotein cholesterol by
      40% to 60%. Monotherapy with atorvastatin (10 to 80 mg/day) is well-tolerated,
      convenient, and appears to be effective for achieving National Cholesterol
      Education Program treatment goals in most patients, regardless of risk status.

PMID- 9264435
TI  - Inverse relation between height and cardiovascular mortality in men during 30
      year follow-up.
AB  - Results from a socioeconomically homogenous population of middle-aged men
      demonstrate that body height predicts total, and especially cardiovascular,
      mortality over a 30-year follow-up, independent of traditional risk factors. The
      results suggest that every 5-cm increase in height is associated with decline of
      cardiovascular mortality risk by 18%.

PMID- 9264436
TI  - Systolic blood pressure at rest, not the degree of beta blockade, predicts the
      result of follow-up tilt-table testing for vasovagal syncope.
AB  - Tilt-table testing after therapy with beta blockade is frequently used to predict
      clinical success. This study found that heart rate and blood pressure reductions
      after beta-blocker therapy did not predict the results of the follow-up tilt
      table test, but low blood pressure at rest before the initial test predicts
      failure of this therapy.

PMID- 9264437
TI  - Active compression cardioversion for refractory atrial fibrillation.
AB  - Application of manual pressure over standard external skin patches during
      cardioversion of atrial fibrillation (active compression cardioversion technique)
      may reduce transthoracic impedance, resulting in improvement in the overall
      cardioversion success rate.

PMID- 9264438
TI  - Long-term clinical experience with a steroid-eluting active fixation ventricular
      electrode in children.
AB  - In this study, the first study performed in pediatric patients, we assessed the
      safety and efficacy of a steroid-eluting active fixation ventricular electrode in
      18 children. Our study shows that steroid-eluting active fixation leads are safe
      and effective in children, and suggests that these leads with their easy
      implantation and low chronic threshold values may be considered as the first
      choice in this age group.

PMID- 9264439
TI  - Persistence of human leukocyte antigen (HLA) antibodies after one year in
      children receiving cryopreserved valved allografts.
AB  - This study shows that the broad anti-HLA antibody response against cryopreserved
      valved allografts used for surgical repair of congenital heart disease persists
      beyond 1 year after implantation. In 3 patients, there were clearly defined HLA
      antibody specificities consistent with the HLA phenotypes of the patients, i.e.,
      the panel-reactive antibody was directed against major alloantigen groups that
      were not expressed by the antibody responders.

PMID- 9264441
TI  - Effects of renal artery stent implantation in patients with renovascular
      hypertension presenting with unstable angina or congestive heart failure.
AB  - This study evaluates the effect of renal artery stent implantation in patients
      with renovascular hypertension presenting with unstable angina (n = 20) or
      congestive heart failure (n = 28). There was a significant improvement in the
      Canadian Cardiovascular Society angina class and the New York Heart Association
      functional class, and at 8.4 +/- 6.4 month follow-up.

PMID- 9264440
TI  - Right ventricular function in patients treated with inhaled nitric oxide after
      cardiac surgery for congenital heart disease in newborns and children.
AB  - Measurement of right ventricular (RV) function is essential for complete
      assessment of the effects of inhaled nitric oxide in the postoperative cardiac
      patient; nitric oxide therapy can result in a decrease in pulmonary vascular
      resistance and improved echocardiographic RV ejection fraction without
      necessarily inducing a significant change in pulmonary artery pressure.

PMID- 9264442
TI  - A novel approach to pediatric intraaortic balloon pump timing using M-mode
      echocardiography.
AB  - Timing balloon inflation and deflation is difficult in pediatric patients
      undergoing intraaortic balloon pumping, because the electrocardiogram and
      arterial pressure tracings are inadequate markers of the onset of diastole and
      systole. M-mode echocardiography provides a precise marker of aortic valve
      opening and closure, as well as balloon motion, and allows accurate timing by
      real-time adjustment of balloon inflation to diastole and deflation to systole.

PMID- 9264444
TI  - Usefulness of transesophageal echocardiography in the assessment of aortic graft
      dehiscence.
AB  - The diagnosis and site of graft dehiscence determined by transesophageal
      echocardiography (TEE), transthoracic echocardiography (TTE), and aortography in
      6 patients, and by computed tomography (CT) scan in 3 patients were compared with
      surgery. Sensitivity of TEE was 100%, aortography 83%, CT scan 67%, and TTE 33%;
      TEE accurately identified severe aortic regurgitation (3), graft narrowing (2),
      distal aortic dissection (1), and a fistulous communication between the aortic
      root and the right ventricle (1) when compared with surgery or aortography.

PMID- 9264443
TI  - Usefulness of atrial septostomy as a treatment for primary pulmonary hypertension
      and guidelines for its application.
AB  - We review our experience and that for 2 large series of atrial septostomy as a
      treatment for advanced pulmonary hypertension to better understand the
      hemodynamic changes that result. Atrial septostomy may be a useful procedure in
      patients with severe refractory pulmonary hypertension, but should not be used in
      patients who are critically ill.

PMID- 9264445
TI  - Relation between patent foramen ovale and perfusion abnormalities in acute
      pulmonary embolism.
AB  - The frequency of right-to-left shunt through a patent foramen ovale is increased
      in hemodynamically stable patients without preexisting cardiopulmonary disease
      with acute pulmonary embolism. This is associated with a greater degree of
      perfusion abnormalities as quantified by perfusion scan and the presence of
      tricuspid regurgitation.

PMID- 9264447
TI  - Cardiovascular screening and emergency procedures at health clubs and fitness
      centers.
AB  - A survey of 110 fitness centers in Massachusetts reveals that many do not follow
      generally accepted guidelines for administering preparticipation cardiovascular
      screening, obtain physician consent for individuals with known cardiovascular
      disease, and prepare for emergency situations should they occur. Thus, the
      promotion of physical activity to the general public now underway in the United
      States must also coincide with better screening at all fitness centers to
      maximize the potential for safe exercise participation at fitness centers.

PMID- 9264446
TI  - Lack of detection of myocardial injury during competitive races of 100 miles
      lasting 18 to 30 hours.
AB  - Competitors in an ultramarathon performed under extreme conditions did not
      demonstrate evidence of subclinical myocardial injury, as determined using
      cardiac troponin T as a marker. This finding refutes previous data and is likely
      due to utilization of an improved assay for cardiac troponin T that minimizes
      cross reactivity with skeletal muscle troponin T.

PMID- 9264448
TI  - Comparison of cine magnetic resonance imaging and Doppler echocardiography for
      evaluation of left ventricular diastolic function.
AB  - Cine magnetic resonance (MR) imaging of the heart detected evidence of left
      ventricular (LV) diastolic filling abnormality in patients with LV wall
      thickening but normal systolic function and normal diastolic function by routine
      Doppler echocardiography. Cine MR imaging may be more sensitive than routine
      echocardiography in detecting abnormalities of LV diastolic function.

PMID- 9264449
TI  - Impact of metoprolol on heart rate, blood pressure, and contractility in normal
      subjects during dobutamine stress echocardiography.
AB  - Dobutamine stress echocardiograms were performed in 6 volunteers under basal
      conditions and after 72 hours of metoprolol, 50 mg twice daily. Although heart
      rate responses were blunted, contractility increased to levels seen before beta
      blockade.

PMID- 9264450
TI  - Histopathology of restenosis after stenting of narrowed coronary arteries after
      cardiac transplantation during the teenage years.
AB  - This study describes the detailed histopathologic appearance of human coronary
      arteries at 3 weeks, and 3 and 7 months after stent implantation in a cardiac
      transplant recipient. There was modest arterial injury associated with stent
      implantation, and immunocytochemistry staining provided evidence that a
      proliferative response from the adventitia contributes to neointimal hyperplasia.

PMID- 9264451
TI  - Are these interviewees actually good role models?

PMID- 9264452
TI  - Dr. Michael E. DeBakey is a great man.

PMID- 9264453
TI  - Dr. Denton A. Cooley is a great surgeon.

PMID- 9264454
TI  - Chaotic atrial rhythm.

PMID- 9264456
TI  - Cell-type specific calcium signalling in a Drosophila epithelium.
AB  - Calcium is a ubiquitous second messenger that plays a critical role in both
      excitable and non-excitable cells. Calcium mobilisation in identified cell types
      within an intact renal epithelium, the Drosophila melanogaster Malpighian tubule,
      was studied by GAL4-directed expression of an aequorin transgene. CAP2b, a
      cardioactive neuropeptide that stimulates fluid secretion by a mechanism
      involving nitric oxide, causes a rapid, dose-dependent rise in cytosolic calcium
      in only a single, genetically-defined, set of 77 principal cells in the main
      (secretory) segment of the tubule. In the absence of external calcium, the CAP2b
      induced calcium response is abolished. In Ca2+-free medium, the endoplasmic
      reticulum Ca2+-ATPase inhibitor, thapsigargin, elevates [Ca2+]i only in the
      smaller stellate cells, suggesting that principal cells do not contain a
      thapsigargin-sensitive intracellular pool. Assays for epithelial function confirm
      that calcium entry is essential for CAP2b to induce a physiological response in
      the whole organ. Furthermore, the data suggest a role for calcium signalling in
      the modulation of the nitric oxide signalling pathway in this epithelium. The
      GAL4-targeting system allows general application to studies of cell-signalling
      and pharmacology that does not rely on invasive or cytotoxic techniques.

PMID- 9264457
TI  - Polarity sorting of actin filaments in cytochalasin-treated fibroblasts.
AB  - The polarity of actin filaments is fundamental for the subcellular mechanics of
      actin-myosin interaction; however, little is known about how actin filaments are
      oriented with respect to myosin in non-muscle cells and how actin polarity
      organization is established and maintained. Here we approach these questions by
      investigating changes in the organization and polarity of actin relative to
      myosin II during actin filament translocation. Actin and myosin II reorganization
      was followed both kinetically, using microinjected fluorescent analogs of actin
      and myosin, and ultrastructurally, using myosin S1 decoration and immunogold
      labelling, in cultured fibroblasts that were induced to contract by treatment
      with cytochalasin D. We observed rapid (within 15 minutes) formation of ordered
      actin filament arrays: short tapered bundles and aster-like assemblies, in which
      filaments had uniform polarity with their barbed ends oriented toward the
      aggregate of myosin II at the base of a bundle or in the center of an aster. The
      resulting asters further interacted with each other and aggregated into bigger
      asters. The arrangement of actin in asters was in sharp contrast to the mixed
      polarity of actin filaments relative to myosin in non-treated cells. At the edge
      of the cell, actin filaments became oriented with their barbed ends toward the
      cell center; that is, the orientation was opposite to what was observed at the
      edge of nontreated cells. This rearrangement is indicative of relative
      translocation of actin and myosin II and of the ability of myosin II to sort
      actin filaments with respect to their polarity during translocation. The results
      suggest that the myosin II-actin system of non-muscle cells is organized as a
      dynamic network where actin filament arrangement is defined in the course of its
      interaction with myosin II.

PMID- 9264458
TI  - A minimal region on the integrin beta4 subunit that is critical to its
      localization in hemidesmosomes regulates the distribution of HD1/plectin in COS-7
      cells.
AB  - The integrin alpha6 beta4 is a major component of hemidesmosomes, in which it
      mediates firm adhesion to laminin 5. Previous studies have shown that the
      incorporation of alpha6 beta4 into hemidesmosomes requires a 303 amino acid
      stretch of the cytoplasmic domain of beta4, comprising part of the first
      fibronectin type III (FNIII) repeat, the second FNIII repeat and the segment that
      connects the second to the third FNIII repeat (connecting segment). Now, we have
      further defined sequences within beta4 that are critical for its localization in
      hemidesmosomes and we demonstrate that these sequences also induce the
      redistribution of HD1/plectin into junctional complexes containing the integrin
      alpha6 beta4 in COS-7 cells, transfected with cDNAs encoding alpha6A and beta4.
      Truncation of the cytoplasmic domain of beta4 after amino acids 1,382 or 1,355 in
      the connecting segment, by which a potential tyrosine activation motif (TAM) is
      removed, does not prevent the localization of alpha6 beta4 in hemidesmosomes in
      the rat bladder carcinoma cell line 804G and neither did it eliminate the ability
      of alpha6 beta4 to change the subcellular distribution of HD1/plectin in COS-7
      cells. In contrast, beta4 subunits in which the entire connecting segment had
      been deleted or which were truncated after amino acid 1,328, which removes almost
      the complete segment, had lost both of these functions. Furthermore, when beta4
      subunits with either a deletion of the second FNIII repeat or a small deletion in
      this repeat were co-expressed with alpha6, the integrins were not localized in
      hemidesmosomes and did not induce the redistribution of HD1/plectin in COS-7
      cells. Finally, the fourth FNIII repeat of beta4 could not replace the second in
      either of these activities. These findings establish that a region in beta4,
      which encompasses the second FNIII repeat and a stretch of 27 amino acids (1,329
      1,355) of the connecting segment, is critical for the localization of alpha6beta4
      in hemidesmosomes and that it regulates the distribution of HD1/plectin.

PMID- 9264459
TI  - Apical sorting of influenza hemagglutinin by transcytosis in retinal pigment
      epithelium.
AB  - The retinal pigment epithelium is endowed with a unique distribution of certain
      plasma membrane proteins. Na+,K+-ATPase, for instance, is polarized to the apical
      surface of RPE, rather than to the basolateral surface as in most other
      epithelia. To study the sorting pathways of RPE cells, we used temperature
      sensitive mutants of influenza and vesicular stomatitis virus (VSV) to
      synchronize the transport of hemagglutinin (HA) and VSV G protein (VSV G) along
      the biosynthetic pathway of the RPE cell line RPE-J. After HA and VSV G
      accumulated in the trans-Golgi network of RPE-J cells kept at 20 degrees C,
      transfer to the permissive temperature (32 degrees C) resulted in the transport
      of both HA and VSV G to the basolateral plasma membrane. Later, while VSV G
      remained basolateral, HA progressively reversed its polarity, eventually becoming
      apical. Further analysis demonstrated that the reversal of HA polarity was due to
      transcytosis of HA from the basolateral to the apical surface of RPE-J cells. To
      determine whether HA followed a transcytotic route in RPE in vivo, influenza and
      VSV were injected into the subretinal space of rat eyes. Again, both HA and VSV G
      were initially observed at the basolateral surface of RPE cells. However, whereas
      VSV G remained there, HA progressively redistributed to the apical surface. These
      findings demonstrated that RPE cells use a transcytotic pathway for the targeting
      of at least some apical proteins to their destination.

PMID- 9264460
TI  - pH gradients are not associated with tip growth in pollen tubes of Lilium
      longiflorum.
AB  - The cytoplasmic pH of growing pollen tubes of Lilium longiflorum Thunb. was
      measured using the pH-sensitive fluorescent dye 2',7'-bis-(carboxyethyl)-5(6')
      carboxyfl uorescein and confocal fluorescence ratio imaging. The average
      cytoplasmic pH in the clear zone of the pollen tube tip was pH 7.11, and no
      consistent pH gradients were detected in the clear zone, averaging around -1.00
      milli pH unit microm(-1), or along the first 50 microm of the tube (3.62 milli pH
      units microm[-1]). In addition, no correlation was observed between the absolute
      tip cytoplasmic pH or the pH gradient and the pollen tube growth rates. Shifts of
      external pH to more acidic pH values (pH 4.5) caused a relatively small
      acidification by 0.18 pH units, whereas a more alkaline external pH >7.0 caused a
      dramatic increase in cytoplasmic pH and growth stopped immediately. Stimulation
      of the plasma membrane H+-ATPase by fusicoccin, resulted in an increase of tube
      growth but no change in cytoplasmic pH. On the other hand, vanadate (250-500
      microM), a putative inhibitor of the pump, stopped tube growth and a slight
      cytoplasmic alkalinisation of 0.1 pH units was observed. Vanadate also arrested
      fusicoccin-stimulated growth and stimulated an increased alkalinisation of around
      0.2 pH units. External application of CaCl2 (10 mM) caused a small acidification
      of less than 0.1 pH units in the clear zone, whilst LaCl3 (250 microM) caused
      slight and rather variable perturbations in cytoplasmic pH of no more than 0.1 pH
      units. Both treatments stopped growth. It was inferred from these data that tip
      acid cytoplasmic pH gradients do not play a central role in the organisation or
      maintenance of pollen tube tip growth.

PMID- 9264461
TI  - TLS (FUS) binds RNA in vivo and engages in nucleo-cytoplasmic shuttling.
AB  - TLS, the product of a gene commonly translocated in liposarcomas (TLS), is
      prototypical of a newly identified class of nuclear proteins that contain a C
      terminal domain with a distinct RNA recognition motif (RRM) surrounded by Arg-Gly
      Gly (RGG) repeats. Its unique N terminus serves as an essential transforming
      domain for a number of fusion oncoproteins in human sarcomas and leukemias. In
      this study we use an in vivo UV crosslinking procedure to probe the interactions
      of TLS with RNA. TLS is found to bind RNA in vivo and the association of TLS with
      RNA is rapidly diminished by treating cells with transcriptional inhibitors. This
      suggests that the species bound by TLS turns over rapidly. Surprisingly, the RRM
      was found to be dispensable for RNA binding by TLS in vivo, suggesting that at
      any one time most of the interactions between TLS and RNA in the cell are not
      sequence specific. Analysis of inter specific heterokaryons formed between human
      and mouse or Xenopus cells revealed that TLS engages in rapid nucleocytoplasmic
      shuttling, a finding confirmed by the ability of anti-TLS antibodies to trap TLS
      when injected into the cytoplasm of HeLa cells. Cellular fractionation
      experiments suggest that TLS binds to RNA in both the nucleus and cytoplasm and
      support the hypothesis that TLS functions as a heterogeneous ribonuclear protein
      (hnRNP)-like chaperone of RNA. These findings are discussed in the context of the
      role altered forms of TLS play in cellular transformation.

PMID- 9264462
TI  - Normal development of preimplantation mouse embryos deficient in gap junctional
      coupling.
AB  - The connexin multigene family (13 characterized members in rodents) encodes the
      subunits of gap junction channels. Gap junctional intercellular coupling,
      established during compaction of the preimplantation mouse embryo, is assumed to
      be necessary for development of the blastocyst. One member of the connexin
      family, connexin43, has been shown to contribute to the gap junctions that form
      during compaction, yet embryos homozygous for a connexin43 null mutation develop
      normally, at least until implantation. We show that this can be explained by
      contributions from one or more additional connexin genes that are normally
      expressed along with connexin43 in preimplantation development. Immunogold
      electron microscopy confirmed that roughly 30% of gap junctions in compacted
      morulae contain little or no connexin43 and therefore are likely to be composed
      of another connexin(s). Confocal immunofluorescence microscopy was then used to
      demonstrate that connexin45 is also assembled into membrane plaques, beginning at
      the time of compaction. Correspondingly, embryos homozygous for the connexin43
      null mutation were found to retain the capacity for cell-to-cell transfer of
      fluorescent dye (dye coupling), but at a severely reduced level and with altered
      permeability characteristics. Whereas mutant morulae showed no evidence of dye
      coupling when tested with 6-carboxyfluorescein, dye coupling could be
      demonstrated using 2',7'-dichlorofluorescein, revealing permeability
      characteristics previously established for connexin45 channels. We conclude that
      preimplantation development in the mouse can proceed normally even though both
      the extent and nature of gap junctional coupling have been perturbed. Despite the
      distinctive properties of connexin43 channels, their role in preimplantation
      development can be fulfilled by one or more other types of gap junction channels.

PMID- 9264463
TI  - A specific domain in alpha-catenin mediates binding to beta-catenin or
      plakoglobin.
AB  - The E-cadherin-catenin adhesion complex has been the subject of many structural
      and functional studies because of its importance in development, normal tissue
      function and carcinogenesis. It is well established that the cytoplasmic domain
      of E-cadherin binds either beta-catenin or plakoglobin, which both can assemble
      alpha-catenin into the complex. Recently we have identified an alpha-catenin
      binding site in beta-catenin and plakoglobin and postulated, based on sequence
      analysis, that these protein-protein interactions are mediated by a hydrophobic
      interaction mechanism. Here we have now identified the reciprocal complementary
      binding site in alpha-catenin which mediates its interaction with beta-catenin
      and plakoglobin. Using in vitro association assays with C-terminal truncations of
      alpha-catenin expressed as recombinant fusion proteins, we found that the N
      terminal 146 amino acids are required for this interaction. We then identified a
      peptide of 27 amino acids within this sequence (amino acid positions 117-143)
      which is necessary and sufficient to bind beta-catenin or plakoglobin. As shown
      by mutational analysis, hydrophobic amino acids within this binding site are
      important for the interaction. The results described here, together with our
      previous work, give strong support for the idea that these proteins associate by
      hydrophobic interactions of two alpha-helices.

PMID- 9264464
TI  - Endocytic pathway from the basal plasma membrane to the ruffled border membrane
      in bone-resorbing osteoclasts.
AB  - We have characterized the convoluted ruffled border (RB) membrane that an
      activated osteoclast maintains against the bone matrix. The bulk of both lgp110
      and rab7, a small GTP-binding protein participating in vesicle fusion to late
      endosomes, was localized to the RB. This indicates that the membrane has some
      characteristics of late endosomal membranes in other cells. Furthermore, the bulk
      of membrane-bound rab7 on the RB suggests that endocytic membrane transport is
      oriented towards the RB in resorbing osteoclasts. Consistently, both lumenal
      horseradish peroxidase and receptor-bound transferrin, a marker of the early
      endosomal recycling pathway, were efficiently endocytosed from the basal plasma
      membrane and delivered to the RB. Delivery of membrane-associated transferrin to
      the RB further indicates that the RB is compositionally different from lysosomes
      and suggests that the endocytic pathway contributes to the maintenance of
      functional RB. In addition to transporting receptor-bound cargo to the RB, the
      endocytic pathway could act in balancing the membrane traffic associated with
      transcytosis from the RB to the basal plasma membrane. Endocytic processes
      (retrieval of mannose 6-phosphate receptors) in osteoclasts appeared to be fairly
      sensitive to bafilomycin A1, a specific inhibitor of vacuolar-type proton
      ATPases. Thus blocking the endocytic membrane traffic towards the RB could
      explain the inactivation of cells by low concentrations of the drug.

PMID- 9264465
TI  - Nuclear distribution of transcription factors in relation to sites of
      transcription and RNA polymerase II.
AB  - We have investigated the spatial relationship between sites containing newly
      synthesized RNA and domains containing proteins involved in transcription, such
      as RNA polymerase II and the transcription factors TFIIH, Oct1, BRG1, E2F-1 and
      glucocorticoid receptors, using dual immunofluorescence labelling followed by
      confocal microscopy on cultured cells. As expected, a high degree of
      colocalisation between the RNA polymerase II and sites containing newly
      synthesised RNA was observed. Like the newly synthesised RNA and the RNA
      polymerase II, we found that all the transcription factors that we studied are
      distributed more or less homogeneously throughout the nucleoplasm, occupying
      numerous small domains. In addition to these small domains, TFIIH was found
      concentrated in coiled bodies and Oct1 in a single large domain of about 1.5
      microm in 30% of the cells in an asynchronous HeLa cell culture. Remarkably, we
      found little or no relationship between the spatial distribution of the
      glucocorticoid receptor, Oct1 and E2F-1 on the one hand and RNA polymerase II and
      transcription sites on the other hand. In contrast, a significant but incomplete
      overlap was observed between the spatial distributions of transcription sites and
      BRG1 and TFIIH. These results indicate that many of the transcription factor-rich
      nuclear domains are not actively involved in transcription. They may represent
      incomplete transcription initiation complexes, inhibitory complexes, or storage
      sites.

PMID- 9264466
TI  - Distinct subunit functions and cell cycle regulated phosphorylation of 20S
      APC/cyclosome required for anaphase in fission yeast.
AB  - We show here that the fission yeast gene products Cut9 and Nuc2 are the subunits
      of the 20S complex, the putative APC (anaphase promoting complex)/cyclosome which
      contains ubiquitin ligase activity required for cyclin and Cut2 destruction. The
      assembly of Cut9 into the 20S complex requires functional Nuc2, and vice versa.
      The size of fission yeast APC/cyclosome is similar to that of higher eukaryotes,
      but differs greatly from that (36S) of budding yeast. The 20S complex is present
      in cells arrested at different stages of the cell cycle, and becomes slightly
      heavier in mitosis than interphase. Cut9 in the 20S complex is
      hyperphosphorylated specifically at the time of metaphase. The truncated forms of
      Cut9 block entry into mitosis, however. The 20S assembly impaired in the cut9
      mutant can be restored by elevating the level of a novel gene product Hcnl,
      similar to budding yeast Cdc26. Furthermore, deletion of protein kinase PKA
      (Pkal) suppresses the phenotype of the cut9 mutation and reduces phosphorylation
      of Cut9. In contrast, PP1 (Dis2) phosphatase mutation shows the reverse effect on
      the phenotype of cut9. The Cut9 subunit is likely to be a target for regulating
      APC/ cyclosome function through protein-protein interactions and phosphorylation.

PMID- 9264467
TI  - Calmodulin localizes to the spindle pole body of Schizosaccharomyces pombe and
      performs an essential function in chromosome segregation.
AB  - The essential calmodulin genes in both Saccharomyces cerevisiae and
      Schizosaccharomyces pombe were precisely replaced with genes encoding fusions
      between calmodulin and the green fluorescent protein (GFP). In living budding
      yeast the GFP-calmodulin fusion protein (GFP-Cmd1p) localized simultaneously to
      sites of cell growth and to the spindle pole body (SPB), the yeast analog of the
      centrosome. Having demonstrated proper localization of GFP-calmodulin in budding
      yeast, we examined the localization of a fusion between GFP and calmodulin (GFP
      Camlp) in fission yeast, where calmodulin had not been localized by any method.
      We find GFP-Camlp also localizes both to sites of polarized cell growth and to
      the fission yeast SPB. The localization of calmodulin to the SPB by GFP fusion
      was confirmed by indirect immunofluorescence. Antiserum to S. pombe calmodulin
      labeled the ends of the mitotic spindle stained with anti-tubulin antiserum. This
      pattern was identical to that seen using antiserum to Sad1p, a known SPB
      component. We then characterized the defects in a temperature-sensitive S. pombe
      calmodulin mutant. Mutant cam1-E14 cells synchronized in S phase completed DNA
      synthesis, but lost viability during transit of mitosis. Severe defects in
      chromosome segregation, including hypercondensation, fragmentation, and unequal
      allocation of chromosomal material were observed. Immunofluorescence analysis of
      tubulin revealed a population of cells containing either broken or mislocalized
      mitotic spindles, which were never observed in wild-type cells. Taken together
      with the subcellular localization of calmodulin, the observed spindle and
      chromosome segregation defects suggest that calmodulin performs an essential role
      during mitosis at the fission yeast SPB.

PMID- 9264468
TI  - DNA damage inhibits proteolysis of the B-type cyclin Clb5 in S. cerevisiae.
AB  - Cell cycle progression is mediated by waves of specific cyclin dependent kinases
      (CDKs) in all eukaryotes. Cyclins are degraded by the ubiquitin pathway of
      proteolysis. The recent identification of several components of the cyclin
      proteolysis machinery has highlighted both the importance of proteolysis at
      multiple transition points in the cell cycle and the involvement of other
      substrates degraded by the same machinery. In this study, we have investigated
      the effects of DNA damage on the cyclin proteolytic machinery in Saccharomyces
      cerevisiae. We find that the half-life of the B-type cyclin Clb5 is markedly
      increased following DNA damage while that of G1 cyclins is not. This effect is
      independent of cell cycle phase. Clb5 turnover requires p34CDC28 activity.
      Stabilisation of Clb5 correlates with an increase in tyrosine phosphorylation of
      p34CDC28, but stabilisation does not require this tyrosine phosphorylation. The
      stabilisation is independent of the checkpoint genes Mec1 and Rad53. These
      observations establish a new link between the regulation of proteolysis and DNA
      damage.

PMID- 9264469
TI  - Glyceraldehyde 3-phosphate dehydrogenase is bound to the fibrous sheath of
      mammalian spermatozoa.
AB  - Evidence is provided that the glycolytic enzyme glyceraldehyde 3-phosphate
      dehydrogenase is covalently linked to the fibrous sheath. The fibrous sheath is a
      typical structure of mammalian spermatozoa surrounding the axoneme in the
      principal piece of the flagellum. More than 90% of boar sperm glyceraldehyde 3
      phosphate dehydrogenase activity is sedimented after cell disintegration by
      centrifugation. Detergents, different salt concentrations or short term
      incubation with chymotrypsin do not solubilize the enzyme, whereas digestion with
      trypsin or elastase does. Short term incubation with trypsin (15 minutes) even
      resulted in an activation of glyceraldehyde 3-phosphate dehydrogenase.
      Purification on phenyl-Sepharose yielded a homogeneous glyceraldehyde 3-phosphate
      dehydrogenase as judged from gel electrophoresis SDS-PAGE and native gradient
      PAGE. The molecular masses are 41.5 and 238 kDa, respectively, suggesting native
      glyceraldehyde 3-phosphate dehydrogenase to be a hexamer. Rabbit polyclonal
      antibodies raised to purified glyceraldehyde 3-phosphate dehydrogenase show a
      high specificity for mammalian spermatozoal glyceraldehyde 3-phosphate
      dehydrogenase, while other proteins of boar spermatozoa or the muscle
      glyceraldehyde 3-phosphate dehydrogenase are not labelled. Immunogold staining
      performed in a post-embedding procedure reveals the localization of
      glyceraldehyde 3-phosphate dehydrogenase along the fibrous sheath in spermatozoa
      of boar, bull, rat, stallion and man. Other structures such as the cell membrane,
      dense fibres, the axoneme or the mitochondria are free of label. During the
      process of sperm maturation, most of the cytoplasm of the sperm midpiece is
      removed as droplets during the passage through the epididymis. The labelling of
      this cytoplasm, in immature boar spermatozoa and in the droplets, indicates that
      glyceraldehyde 3-phosphate dehydrogenase is completely removed from the midpiece
      during sperm maturation in the epididymis. The inverse compartmentation of the
      glycolytic enzyme and mitochondria in the mammalian sperm flagella suggests that
      ATP-production in the principal piece mainly occurs by glycolysis and in the
      midpiece by respiration.

PMID- 9264470
TI  - Intracoronary brachytherapy: the death knell of restenosis or just another
      episode of a never-ending story?

PMID- 9264471
TI  - Pacifying the infarct vessel.

PMID- 9264472
TI  - Pulmonary embolism thrombolysis: broadening the paradigm for its administration.

PMID- 9264473
TI  - Coronary and myocardial blood volumes: noninvasive tools to assess the coronary
      microcirculation?

PMID- 9264474
TI  - Endothelial function, insulin sensitivity, and hypertension.

PMID- 9264475
TI  - Long-term angiographic and clinical outcome after percutaneous transluminal
      coronary angioplasty and intracoronary radiation therapy in humans.
AB  - BACKGROUND: Ionizing radiation has been shown to reduce neointimal formation
      after balloon angioplasty in experimental models of restenosis. This study was
      designed to evaluate the feasibility, safety, and effectiveness of intracoronary
      radiation therapy (ICRT) after percutaneous transluminal coronary angioplasty
      (PTCA) for preventing restenosis in human coronary arteries. METHODS AND RESULTS:
      Twenty-one patients (22 arteries) with unstable angina underwent standard balloon
      angioplasty. ICRT was performed with the use of an 192Ir source wire that was
      hand delivered to the angioplasty site. Angiographic follow-up was performed at
      24 hours, between 30 and 60 days, and at 6 months. Angioplasty was successful in
      19 of 22 lesions, and insertion of the radioactive source wire was successful at
      all treated sites. Angiographic study at 24 hours demonstrated early late loss of
      the luminal diameter from 1.92+/-0.55 to 1.40+/-0.27 mm. Between 30 and 60 days,
      repeat angiography demonstrated total occlusion in 2 arteries, a new
      pseudoaneurysm in 1 artery, and significant dilatation at the treatment site in 2
      additional vessels. At > or = 6 months' follow-up, all remaining arteries (n=20)
      maintained patent, with a mean lumen diameter of 1.65+/-0.8 mm. The calculated
      late lumen loss was 0.27+/-0.56 mm, and the late loss index was 0.19. Clinical
      events at 1 year included myocardial infarction in 1 patient, repeat angioplasty
      to the treated site in 3 patients, and persistent angina in 7 patients.
      CONCLUSIONS: These preliminary results demonstrate that ICRT after coronary
      intervention is feasible and is associated with an acceptable degree of
      complications and lower rates of angiographic restenosis indexes.

PMID- 9264476
TI  - Lipoprotein lipase variants D9N and N291S are associated with increased plasma
      triglyceride and lower high-density lipoprotein cholesterol concentrations:
      studies in the fasting and postprandial states: the European Atherosclerosis
      Research Studies.
AB  - BACKGROUND: Variations at the DNA level with moderate effects on biochemical
      variables may be important for the occurrence of disease at the population level,
      if they are common. Two mutations in the LPL gene, N9 and S291, are associated
      with variation in fasting plasma concentrations of HDL cholesterol (HDL-C) and
      triglycerides (TG). We investigated whether these mutants were more frequent in
      offspring of cases with premature coronary disease and analyzed the effects on
      fasting plasma lipids and postprandial TG. METHODS AND RESULTS: Students with and
      without paternal history of myocardial infarction (cases and control subjects
      [controls]) were studied in the European Atherosclerosis Research Studies I and
      II (EARS-I and -II). Allelic frequencies for the N9 and S291 mutations did not
      differ between cases and control subjects. The N9 mutation was identified in 4.2%
      of all subjects in EARS-I, and carriers had higher fasting TG levels (P<.001)
      than noncarriers. In an oral fat tolerance test, there were no differences in
      postprandial TG between carriers and noncarriers of the N9 allele. The S291
      mutation was identified in 3.1% of all subjects in EARS-I, and carriers had lower
      fasting HDL-C levels (P<.005) than noncarriers. There was a significant
      interaction between S291 genotype and body mass index on fasting TG levels
      (P<.01). In the cases, carriers of the S291 allele had higher TG levels 6 hours
      postprandially (P<.04) than did noncarriers. CONCLUSIONS: The two LPL mutations
      are common and may predispose to elevated TG and decreased HDL-C concentrations,
      even in young subjects. In the case of the S291 mutation, this effect appears to
      be mediated via delayed postprandial TG clearance. Moreover, even moderate
      obesity potentiates the TG-raising and HDL-lowering effects associated with the
      S291 allele.

PMID- 9264477
TI  - Association of angiotensin-converting enzyme gene I/D polymorphism with change in
      left ventricular mass in response to physical training.
AB  - BACKGROUND: The absence (deletion allele [D]) of a 287-base pair marker in the
      ACE gene is associated with higher ACE levels than its presence (insertion allele
      [I]). If renin-angiotensin systems regulate left ventricular (LV) growth, then
      individuals of DD genotype might show a greater hypertrophic response than those
      of II genotype. We tested this hypothesis by studying exercise-induced LV
      hypertrophy. METHODS AND RESULTS: Echocardiographically determined LV dimensions
      and mass (n=140), electrocardiographically determined LV mass and frequency of LV
      hypertrophy (LVH) (n=121), and plasma brain natriuretic peptide (BNP) levels
      (n=49) were compared at the start and end of a 10-week physical training period
      in male Caucasian military recruits. Septal and posterior wall thicknesses
      increased with training, and LV mass increased by 18% (all P<.0001). Response
      magnitude was strongly associated with ACE genotype: mean LV mass altered by
      +2.0, +38.5, and +42.3 g in II, ID and DD, respectively (P<.0001). The prevalence
      of electrocardiographically defined LVH rose significantly only among those of DD
      genotype (from 6 of 24 before training to 11 of 24 after training, P<.01). Plasma
      brain natriuretic peptide levels rose by 56.0 and 11.5 pg/mL for DD and II,
      respectively (P<.001). CONCLUSIONS: Exercise-induced LV growth in young males is
      strongly associated with the ACE I/D polymorphism.

PMID- 9264478
TI  - Danish multicenter randomized study of invasive versus conservative treatment in
      patients with inducible ischemia after thrombolysis in acute myocardial
      infarction (DANAMI). DANish trial in Acute Myocardial Infarction.
AB  - BACKGROUND: The aim of the DANish trial in Acute Myocardial Infarction (DANAMI)
      study was to compare an invasive strategy of percutaneous transluminal coronary
      angioplasty (PTCA) or coronary artery bypass grafting (CABG) with a conservative
      strategy in patients with inducible myocardial ischemia who received thrombolytic
      treatment for a first acute myocardial infarction (AMI). METHODS AND RESULTS: Of
      the 503 patients randomized to an invasive strategy, PTCA was performed in 266
      (52.9%) and CABG in 147 (29.2%) from 2 to 10 weeks after the AMI. Of the 505
      patients in the conservative treatment group, only 8 (1.6%) had been
      revascularized 2 months after the AMI. The patients were followed up from 1 to
      4.5 years. The primary end points were mortality, reinfarction, and admission
      with unstable angina. At 2.4 years' follow-up (median), mortality was 3.6% in the
      invasive treatment group and 4.4% in the conservative treatment group (not
      significant). Invasive treatment was associated with a lower incidence of AMI
      (5.6% versus 10.5%; P=.0038) and a lower incidence of admission for unstable
      angina (17.9% versus 29.5%; P<.00001). The percentages of patients with a primary
      end point were 15.4% and 29.5% at 1 year, 23.5% and 36.6% at 2 years, and 31.7%
      versus 44.0% at 4 years (P=<.00001) in the invasive and conservative treatment
      groups, respectively. At 12 months, stable angina pectoris was present in 21% of
      patients in the invasive treatment group and 43% in the conservative treatment
      group. CONCLUSIONS: Invasive treatment in post-AMI patients with inducible
      ischemia results in a reduction in the incidence of reinfarction, fewer
      admissions due to unstable angina, and lower prevalence of stable angina. We
      conclude that patients with inducible ischemia before discharge who have received
      treatment with thrombolytic drugs for their first AMI should be referred to
      coronary arteriography and revascularized accordingly.

PMID- 9264479
TI  - Prostacyclin receptor desensitization is a reversible phenomenon in human
      platelets.
AB  - BACKGROUND: Long-term exposure of platelets to endogenous or exogenous
      prostacyclin or its analogues might result in desensitization of the platelet
      prostacyclin receptor in vitro and in vivo accompanied by a loss in receptor
      density on the platelet surface and a reduced sensitivity toward the inhibitory
      effects of prostacyclins. However, the reversibility of this process in platelets
      has not yet been investigated. METHODS AND RESULTS: Human platelets desensitized
      by the chemically stable prostacyclin analogue iloprost showed a significant
      reduction in [3H]-iloprost binding sites that was reversed by saponin
      permeabilization. This indicates functionally active internalized prostacyclin
      receptors. To assess whether the internalized prostacyclin receptors recycle to
      the cell surface after withdrawal of the agonist, iloprost sensitivity and
      prostacyclin receptor binding properties of iloprost (30 nmol/L, 2 hours)
      desensitized platelets incubated in iloprost-free autologous plasma were
      investigated. While desensitized platelets showed a significant increase in IC50
      for iloprost inhibition of thrombin-induced platelet aggregation, serotonin
      release, and p-selectin expression and a reduced iloprost-stimulated cAMP
      formation, platelet iloprost sensitivity was restored 3 hours after iloprost
      withdrawal. In addition, the significant reduction in Bmax and the increase in
      K(D) of prostacyclin receptors in desensitized platelets as revealed by [3H]
      iloprost binding studies also returned to the initial values. CONCLUSIONS: These
      results indicate that prostacyclin receptors internalized during short-term
      desensitization are not degraded but can be recycled rapidly to the platelet
      surface in a functionally active form after withdrawal of the agonist.

PMID- 9264480
TI  - Clearance of tissue plasminogen activator (TPA) and TPA/plasminogen activator
      inhibitor type 1 (PAI-1) complex: relationship to elevated TPA antigen in
      patients with high PAI-1 activity levels.
AB  - BACKGROUND: To evaluate the effect of plasminogen activator inhibitor type 1 (PAI
      1) levels on the clearance of total tissue plasminogen activator (TPA) antigen,
      we studied the clearance of active TPA and TPA/PAI-1 complex in subjects with low
      (181+/-109 pmol/L; n=7) and high (1166+/-322 pmol/L; n=4) baseline active PAI-1.
      METHODS AND RESULTS: A 5-microg/kg bolus of TPA was infused over a 15-second
      period followed by measurement of TPA activity, TPA antigen, TPA/PAI-1, TPA/C1
      inhibitor, PAI-1 activity, and PAI-1 antigen over a 4-hour period. alpha-Phase
      clearance of total TPA antigen was faster in subjects with low PAI-1 (t(1/2) of
      3.5+/-0.7 minutes) versus high PAI-1 (t(1/2) of 5.3+/-0.9 minutes) (P=.006).
      Clearance of all factors was best fit by a two-compartment pharmacokinetic model
      based on a computer-simulated human circulatory system. The average hepatic
      clearance fraction in the two-compartment model was greater for active TPA (89+/
      10%, t(1/2) of 2.4+/-0.3 minutes) than for TPA/PAI-1 complex (48+/-17%, t(1/2) of
      5.0+/-1.8 minutes) (P=.0006). CONCLUSIONS: Plasma clearance of active TPA was
      faster than clearance of TPA/PAI-1 complex. High levels of active PAI-1 converted
      more TPA into TPA/PAI-1 complex, effectively slowing the clearance of total TPA
      antigen and explaining in part why high levels of PAI-1 activity are associated
      with increases in total TPA antigen.

PMID- 9264481
TI  - Comparison of the effects of two doses of recombinant hirudin compared with
      heparin in patients with acute myocardial ischemia without ST elevation: a pilot
      study. Organization to Assess Strategies for Ischemic Syndromes (OASIS)
      Investigators.
AB  - BACKGROUND: Despite the use of aspirin and heparin, patients with acute ischemic
      syndromes are at risk of myocardial infarction (MI) or refractory ischemia.
      Therefore, evaluation of more potent antithrombotic therapies is warranted.
      METHODS AND RESULTS: Patients (n=909) with unstable angina or suspected acute MI
      without ST-segment elevation were randomized to receive heparin (5000 IU
      bolus+1000 to 1200 U/h, n=371), low-dose hirudin (LDHir) (0.2 mg/kg bolus+0.10 mg
      x kg(-1) x h(-1) infusion, n=271), or medium-dose hirudin (MDHir) (0.4 mg/kg
      bolus+0.15 mg x kg(-1) x h(-1) infusion, n=267) for 72 hours. At 7 days, 6.5% of
      patients in the heparin group, 4.4% in the LDHir group, and 3.0% in the MDHir
      group (P=.267 heparin versus low-dose hirudin; P=.047 heparin versus medium-dose
      hirudin) suffered cardiovascular death, new MI, or refractory angina (primary
      outcome). The proportions with cardiovascular death, new MI, or refractory or
      severe angina (secondary outcome) were 15.6%, 12.5%, and 9.4%, respectively
      (P=.27 for heparin versus LDHir; P=.02 for heparin versus MDHir). The rates of
      new MI were 4.9%, 2.6%, and 1.9%, respectively (P=.14 heparin versus LDHir;
      P=.046 heparin versus MDHir). Fewer patients underwent coronary artery bypass
      graft surgery in the two hirudin groups (3.7% low-dose, 1.1% medium-dose group)
      compared with heparin (4.0%) (P=.028 for heparin versus MDHir). After cessation
      of study treatments, there was an increase in ischemic events in the LDHir group
      at approximately 24 hours and at approximately 5 days in the medium-dose group.
      Nevertheless, at 180 days, the differences between hirudin and heparin persisted.
      CONCLUSIONS: Hirudin, especially at the medium dose, appears to be superior to
      heparin in preventing ischemic outcomes in unstable angina or acute MI without ST
      elevation.

PMID- 9264482
TI  - C-reactive protein as a predictor of infarct expansion and cardiac rupture after
      a first Q-wave acute myocardial infarction.
AB  - BACKGROUND: Pump failure after acute myocardial infarction (AMI) can be predicted
      by several indices that estimate infarct size. However, there are few indices
      that predict infarct expansion and cardiac rupture. We focused on the prognostic
      significance of serum C-reactive protein (CRP) after AMI. METHODS AND RESULTS:
      Serum CRP levels were measured every 24 hours in 220 patients with a first Q-wave
      AMI. In-hospital complications, predischarge left ventriculographic findings, and
      long-term prognosis were assessed in relation to peak CRP levels. Peak levels of
      both CRP and creatine kinase (CK) were higher in patients with pump failure than
      in those without pump failure. In patients with cardiac rupture, peak CRP levels
      were higher than in those without rupture (P=.001); peak CK levels were not
      predictive. Higher CRP levels were found in patients with left ventricular
      aneurysm (P=.001 versus those without), aggravated heart failure (P=.03 versus
      those without), and cardiac death (P<.0001 versus survivors) during the first
      year after AMI. Multivariate analysis confirmed that an elevation of the peak CRP
      level > or = 20 mg/dL was an independent predictor of cardiac rupture (relative
      risk, 4.72; P=.004), left ventricular aneurysmal formation (relative risk, 2.11;
      P=.03), and 1-year cardiac death (relative risk, 3.44; P<.0001). CONCLUSIONS:
      Cardiac rupture, left ventricular aneurysmal formation, and 1-year cardiac death
      were associated with an elevation of serum CRP early after AMI, suggesting that
      elevation of CRP levels after AMI may predict infarct expansion.

PMID- 9264483
TI  - Detection of coronary artery disease with myocardial contrast echocardiography:
      comparison with 99mTc-sestamibi single-photon emission computed tomography.
AB  - BACKGROUND: The purpose of this study was to determine whether myocardial
      contrast echocardiography (MCE) can be used to detect coronary artery disease
      (CAD) during rest and pharmacological stress in humans through the use of venous
      injections of contrast. METHODS AND RESULTS: Thirty patients with known or
      suspected CAD underwent MCE and 99mTc-sestamibi single-photon emission computed
      tomography (SPECT) at baseline and after dipyridamole (0.56 mg x kg(-1))
      infusion. Ten myocardial segments (5 each in the apical two- and four-chamber
      views) from the two sets of images using both methods were scored for myocardial
      perfusion as follows: 1=normal, 0.5=mildly reduced, and 0=severely reduced. The
      information from baseline and postdipyridamole images was then used to determine
      whether an abnormal segment was irreversible (similar abnormal perfusion at
      baseline and after dipyridamole) or reversible (perfusion better at baseline
      compared with after dipyridamole). Concordance between segmental scores was 92%
      (kappa=.99) for both methods. Concordance between normal perfusion and reversible
      or irreversible segmental defects was 90% (kappa=.80). Agreem between the two
      methods for each of the three vascular territories in each patient was 90%
      (kappa=.77), while agreement for the presence or absence of CAD in each patient
      was 86% (kappa=.86). In the 4 patients with disagreement, the perfusion scores
      were 0.5 for SPECT and 1.0 for MCE. CONCLUSIONS: This study shows that MCE, with
      venous injection of contrast, can define the presence of CAD during rest and
      pharmacological stress. The location of perfusion abnormalities and their
      physiologic relevance (reversible or irreversible) by MCE is similar to that
      provided by SPECT. MCE, therefore, holds promise for the noninvasive assessment
      of myocardial perfusion in humans.

PMID- 9264484
TI  - Improved outcome after coronary bypass surgery in patients with ischemic
      cardiomyopathy and residual myocardial viability.
AB  - BACKGROUND: Although residual myocardial viability in patients with coronary
      artery disease and extensive regional asynergy is associated with improved
      ventricular function after coronary bypass surgery, the relationship between
      viability and clinical outcome after surgery is unclear. We hypothesized that
      patients with poor ventricular function and predominantly viable myocardium have
      a better outcome after bypass surgery compared with those with less viability.
      METHODS AND RESULTS: Seventy patients with multivessel coronary artery disease
      and left ventricular ejection fractions < 40% who underwent preoperative
      quantitative 201Tl scintigraphy before coronary bypass surgery were analyzed
      retrospectively. 201Tl scintigrams were reviewed blindly, and each segment was
      assigned a score based on defect magnitude. Segmental viability scores were
      summed and divided by the number of segments visualized to determine a viability
      index. The viability index was significantly related to 3-year survival free of
      cardiac event (cardiac death or heart transplant) after bypass surgery (P=.011)
      and was independent of age, ejection fraction, and number of diseased coronary
      vessels. Patients with greater viability (group 1; viability index > 0.67; n=33)
      were similar to patients with less viability (group 2; viability index < or =
      0.67; n=37) with respect to age, comorbidities, and extent of coronary artery
      disease. There were 6 cardiac deaths and no heart transplants in group 1 patients
      and 15 cardiac deaths and two transplants in group 2 patients. Survival free of
      cardiac death or transplantation was significantly better in group 1 patients on
      Kaplan-Meier analysis (P=.018). CONCLUSIONS: We conclude that resting 201Tl
      scintigraphy may be useful in preoperative risk stratification for identification
      of patients more likely to benefit from surgical revascularization.

PMID- 9264485
TI  - Dynamics of left ventricular apex rotation during angioplasty: a sensitive index
      of ischemic dysfunction.
AB  - BACKGROUND: Apex rotation has been shown to provide a reliable index of the
      dynamics of left ventricular (LV) twist. In this study, we aimed to characterize
      twist at baseline and during acute ischemia in 20 patients undergoing
      percutaneous transluminal coronary angioplasty to the left anterior descending
      (LAD) artery and to test whether an old myocardial infarction or collateral flow
      affected twist dynamics. METHODS AND RESULTS: Among patients with no previous
      infarction, five had no collaterals (group A) and six had angiographically
      visible collaterals (group B). Previous anterior infarction was present in nine
      patients (group C). Data were acquired with the LAD angioplasty wire passed
      beyond the apex using a view aligned with the LV long axis. Frame-by-frame
      dynamics of apex rotation were measured from the angular movement of the portion
      of the wire that traversed the apex. Aortic pressure recordings allowed precise
      temporal definition of the cardiac cycle. Dynamics of apex rotation were measured
      at fixed intervals until 60 seconds of occlusion and up to 60 seconds of
      reperfusion. In group A, counterclockwise apex rotation (twist) during ejection
      of -22.0+/-1.7 degrees (mean+/-SEE) was followed by rapid clockwise rotation
      (untwist) during isovolumic relaxation. During 60 seconds of ischemia, maximum
      apex rotation decreased to -8.2+/-2.0 degrees (P<.001 versus baseline). In group
      B, baseline apex rotation was similar (-26.2+/-6.9 degrees) to that in group A,
      but ischemia had less effect, with apex rotation values of -17.7+/-3.4 degrees
      (P<.05 versus group A values). Group C was characterized by reduced baseline apex
      rotation values (-9.7+/-3.1 degrees, P<.05 versus group A values), with little
      change observed during ischemia (-8.1+/-2.6 degrees). CONCLUSIONS: Apex rotation,
      an index of ventricular twist, is sensitive to acute ischemia in patients without
      previous myocardial infarction. Visible collaterals to the ischemic region
      attenuate the acute ischemic response at 60 seconds. Previous myocardial
      infarction causes abnormalities in the baseline twist pattern with no further
      deterioration at 60 seconds of ischemia.

PMID- 9264486
TI  - Coronary angiographic characteristics of patients with permanent artificial
      pacemakers.
AB  - BACKGROUND: The cause of severe cardiac conduction disturbances is often
      uncertain. The aim of this study was to examine a group of patients with
      permanent pacemakers who underwent coronary arteriography to determine the extent
      of coronary atherosclerotic disease that might be responsible for the conduction
      disturbances. METHODS AND RESULTS: Forty-three consecutive patients with a
      permanent pacemaker and 36 matched control patients were investigated. The
      coronary angiographic study included measurement of diameter and stenosis
      severity, qualitative assessment of flow, and classification of pathological
      anatomy, particularly the blood supply to territories supplying the different
      segments of the conduction system. Among 43 patients with a permanent pacemaker,
      27 had ischemic heart disease (17 after coronary artery bypass graft surgery).
      The conduction disturbance was infranodal in 28 patients, sinus nodal in 6, AV
      nodal in 4, and complete AV block of unspecified origin in 5. Patients with
      permanent pacemakers had a coronary artery pathology compromising blood flow to
      the septal branches and the right coronary artery (type IV anatomy). This pattern
      was significantly different from the matched control patients, in whom the most
      prevalent coronary anatomy was the combination of right coronary artery with
      distal left anterior descending artery (not involving the septal branches)
      lesions (P=.007). CONCLUSIONS: Patients with coronary artery disease and severe
      conduction disturbances that require implantation of permanent pacemakers are
      more likely to have a specific pathological coronary anatomy that combines a
      compromised blood flow to the septal branches of the left anterior descending
      artery with right coronary artery lesions. The location of lesions in the
      coronary tree rather than severe diffuse atherosclerosis appears to be
      responsible for the conduction disturbances.

PMID- 9264487
TI  - Postextrasystolic potentiation and dobutamine echocardiography in predicting
      recovery of myocardial function after coronary bypass revascularization.
AB  - BACKGROUND: Identification of viable but hibernating myocardium remains a
      relevant issue in the current era of myocardial revascularization.
      Echocardiography can be helpful in detecting reversible contractile dysfunction
      and optimizing the selection of patients for coronary bypass surgery. METHODS AND
      RESULTS: Eighty-four consecutive candidates for bypass surgery with chronic
      multivessel coronary artery disease were screened, and 60 were included in this
      prospective study. Preoperative evaluation of a reversible contractile
      dysfunction in asynergic myocardial regions was performed by dobutamine infusion
      at 5 (low dose) and 10 (intermediate dose) microg x kg(-1) x min(-1) with each
      stage lasting at least 5 minutes; postextrasystolic potentiation (PESP), with a
      coupling interval ranging from 500 to 300 ms with a progressive 10-ms decrease;
      or a combination of both dobutamine infusion and PESP. Sensitivity (92% versus
      86%) and predictive accuracy (89% versus 84%) were higher with PESP than
      dobutamine (P=.009 and P=.001, respectively), but the combination did not improve
      sensitivity or accuracy. Dobutamine induced ischemic dysfunction in 15% of
      patients at the intermediate dose; however, the low dose resulted in loss of
      sensitivity. CONCLUSIONS: PESP echocardiography is a useful and cost-effective
      method to identify viable myocardium in patients with multivessel coronary
      disease undergoing revascularization and is more sensitive and accurate than
      dobutamine infusion.

PMID- 9264488
TI  - Abnormal cardiac adrenergic nerve function in patients with syndrome X detected
      by [123I]metaiodobenzylguanidine myocardial scintigraphy.
AB  - BACKGROUND: Previous studies have suggested that an abnormal cardiac adrenergic
      tone may have a pathophysiological role in syndrome X (effort angina, positive
      exercise testing, angiographically normal coronary arteries). METHODS AND
      RESULTS: To evaluate cardiac adrenergic nerve function, we performed
      [123I]metaiodobenzylguanidine (MIBG) myocardial scintigraphy in 12 patients with
      syndrome X and 10 control subjects. Cardiac MIBG uptake was assessed by the
      heart/mediastinum (H/M) ratio and by an MIBG uptake defect score (higher
      values=lower uptake). In syndrome X patients, we also correlated MIBG
      scintigraphic findings with stress myocardial perfusion as assessed by 201Tl
      scintigraphy. An inferior MIBG defect was observed in only 1 control subject,
      whereas 9 patients (P<.01) showed MIBG defects. The heart was totally or almost
      totally invisible on MIBG images in 5 patients, and predominantly regional
      defects were observed in 4. The H/M ratio was lower (1.70+/-0.6 versus 2.2+/-0.3,
      P=.03) and MIBG uptake defect score higher (35+/-31 versus 4+/-2, P=.003) in
      syndrome X patients. Reversible stress thallium perfusion defects were found in
      62% of patients with MIBG defects but in no patient with normal MIBG uptake. MIBG
      defects persisted unchanged in 7 patients at a 5+/-3-month follow-up study.
      CONCLUSIONS: In this study, obvious defects in global and/or regional cardiac
      MIBG uptake, indicating an abnormal cardiac adrenergic nerve function, were
      detected in 75% of patients with syndrome X. These findings strongly support the
      cardiac origin of chest pain in syndrome X, although the mechanisms and the
      pathophysiological meaning of the abnormal cardiac MIBG uptake in these patients
      deserve further investigation.

PMID- 9264489
TI  - Clinical significance of mitral regurgitation after acute myocardial infarction.
      Survival and Ventricular Enlargement Investigators.
AB  - BACKGROUND: Mitral regurgitation (MR) may complicate acute myocardial infarction
      (MI). However, it is not known whether mild MR is an independent predictor of
      post-MI outcome. METHODS AND RESULTS: The study cohort consisted of 727 Survival
      and Ventricular Enlargement Study patients who underwent cardiac catheterization,
      including left ventriculography, up to 16 days after MI. Left ventriculograms
      were analyzed for diastolic and systolic volumes, global left ventricular
      sphericity, extent of wall motion abnormality, and endocardial curvature. The
      presence of MR was related to the risk of developing a cardiovascular event
      during 3.5 years of follow-up. MR was present in 141 patients (19.4%). Severe
      (3+) MR was present in only 2 patients. Patients with MR were more likely to have
      a persistently occluded infarct artery (MR versus no MR, 27.3% versus 15.2%;
      P=.001). Although the ejection fractions were similar, MR patients had larger end
      systolic and end-diastolic volumes and more spherical ventricles than patients
      without MR. Sphericity change from diastole to systole was also significantly
      reduced in MR patients. Patients with MR were more likely to experience
      cardiovascular mortality (29% versus 12%; P<.001), severe heart failure (24%
      versus 16%; P=.0153), and the combined end point of cardiovascular mortality,
      severe heart failure, or recurrent myocardial infarction (47% versus 29%;
      P<.001). The presence of MR was an independent predictor of cardiovascular
      mortality (relative risk, 2.00; 95% CI, 1.28 to 3.04). CONCLUSIONS: Mild MR is an
      independent predictor of post-MI mortality. As such, it adds important
      information for risk stratification of post-MI patients.

PMID- 9264490
TI  - Changes in phasic coronary blood flow velocity profile and relative coronary flow
      reserve in patients with hypertrophic obstructive cardiomyopathy.
AB  - BACKGROUND: In this study, we both investigated coronary flow velocity in
      hypertrophic obstructive cardiomyopathy (HOCM) and tested the hypothesis of
      differing coronary flow reserve (CFR) of coronary arteries perfusing left
      ventricular regions with nonuniform myocardial hypertrophy by measuring the
      relative CFR. METHODS AND RESULTS: Coronary flow velocity was assessed in left
      anterior descending coronary (LAD) and left circumflex (LCX) arteries in 18
      patients with HOCM and marked hypertrophy only in the ventricular septum, in 13
      patients without obstruction (HCM), and in 9 age- and sex-matched normal subjects
      at rest, during rapid atrial pacing, and after dobutamine infusion (5 to 30
      microg/kg per minute). Relative CFR was estimated as the ratio between absolute
      CFR of the LAD and absolute CFR of the LCX (LAD/LCX(CF)). At the peak of rapid
      atrial pacing and during dobutamine stress, LAD/LCX(CF) was reversed in HOCM
      patients (from 1.25+/-0.11 to 0.82+/-0.07 and 0.79+/-0.06, respectively), whereas
      it remained unchanged in control subjects (from 1.0+/-0.1 to 1.0+/-0.05 and 1.0+/
      0.05, respectively; P<.001). In HCM patients, LAD/LCX(CF) at rest was 1.10+/
      0.11, whereas during rapid atrial pacing and dobutamine stress, it was 0.92+/
      0.08 and 0.90+/-0.09, respectively. Relative CFR was 0.62+/-0.05 in HOCM patients
      and 1.05+/-0.05 (P<.001) in normal subjects. There was an inverse correlation
      between relative CFR and peak systolic outflow tract gradient (r2=.74, P<.001).
      CONCLUSIONS: Regional distribution of hypertrophy in some patients with HOCM
      resulted in regional impairment of coronary flow. Relative CFR can be used to
      estimate regional disturbances of coronary flow and may help in patient selection
      for new interventional therapeutic techniques.

PMID- 9264491
TI  - Predicting survival in heart failure case and control subjects by use of fully
      automated methods for deriving nonlinear and conventional indices of heart rate
      dynamics.
AB  - BACKGROUND: Despite much recent interest in quantification of heart rate
      variability (HRV), the prognostic value of conventional measures of HRV and of
      newer indices based on nonlinear dynamics is not universally accepted. METHODS
      AND RESULTS: We have designed algorithms for analyzing ambulatory ECG recordings
      and measuring HRV without human intervention, using robust methods for obtaining
      time-domain measures (mean and SD of heart rate), frequency-domain measures
      (power in the bands of 0.001 to 0.01 Hz [VLF], 0.01 to 0.15 Hz [LF], and 0.15 to
      0.5 Hz [HF] and total spectral power [TP] over all three of these bands), and
      measures based on nonlinear dynamics (approximate entropy [ApEn], a measure of
      complexity, and detrended fluctuation analysis [DFA], a measure of long-term
      correlations). The study population consisted of chronic congestive heart failure
      (CHF) case patients and sex- and age-matched control subjects in the Framingham
      Heart Study. After exclusion of technically inadequate studies and those with
      atrial fibrillation, we used these algorithms to study HRV in 2-hour ambulatory
      ECG recordings of 69 participants (mean age, 71.7+/-8.1 years). By use of
      separate Cox proportional-hazards models, the conventional measures SD (P<.01),
      LF (P<.01), VLF (P<.05), and TP (P<.01) and the nonlinear measure DFA (P<.05)
      were predictors of survival over a mean follow-up period of 1.9 years; other
      measures, including ApEn (P>.3), were not. In multivariable models, DFA was of
      borderline predictive significance (P=.06) after adjustment for the diagnosis of
      CHF and SD. CONCLUSIONS: These results demonstrate that HRV analysis of
      ambulatory ECG recordings based on fully automated methods can have prognostic
      value in a population-based study and that nonlinear HRV indices may contribute
      prognostic value to complement traditional HRV measures.

PMID- 9264492
TI  - Insulin sensitivity, vascular reactivity, and clamp-induced vasodilatation in
      essential hypertension.
AB  - BACKGROUND: Insulin resistance and vascular abnormalities have both been
      described in patients with essential hypertension. Whether these defects are
      associated with one another in the same individual has not been established.
      METHODS AND RESULTS: Whole-body insulin sensitivity (by the insulin clamp
      technique), forearm minimal vascular resistances, and the dose-response curve to
      acetylcholine, sodium-nitroprusside, and norepinephrine were measured in a group
      of 29 male patients with untreated essential hypertension. When the patients were
      divided into tertiles according to their level of insulin sensitivity, resistant
      and sensitive hypertensives were matched on several potential confounders of
      insulin action and vascular function. These subgroups showed similar minimal
      vascular resistances (2.5+/-0.2 versus 3.2+/-0.6 mm Hg per mL x min(-1) x dL(-1))
      and superimposable responses to graded intraarterial infusions of acetylcholine,
      sodium-nitroprusside, and norepinephrine. No correlation was found between the
      vascular parameters (slope of the curve or maximal response) and insulin-mediated
      glucose uptake in the whole group. During the clamp, insulin sensitive patients
      tended to have greater increments in forearm blood flow when compared to their
      insulin resistant counterparts (+53+/-21 versus +9+/-7%, P=.06); in the whole
      group, clamp-induced vasodilatation was weakly related to insulin-mediated
      glucose uptake (r=.44, P<.02) as well as to the slope of the acetylcholine dose
      response curve (r=.40, P<.04). Together, these two responses explained 30%
      (multiple r=.55, P<.01) of the variability in insulin-induced vasodilatation.
      CONCLUSIONS: Metabolic insulin resistance in essential hypertension is not
      associated with abnormalities in vascular structure, acetylcholine or
      nitroprusside-induced vasodilatation, or vascular adrenergic reactivity. Degree
      of insulin sensitivity and acetylcholine sensitivity explain a small portion of
      the variability of the clamp-induced vasodilatation in hypertensive patients.

PMID- 9264493
TI  - Effect of the calcium antagonist felodipine as supplementary vasodilator therapy
      in patients with chronic heart failure treated with enalapril: V-HeFT III.
      Vasodilator-Heart Failure Trial (V-HeFT) Study Group.
AB  - BACKGROUND: Despite therapy with diuretics, ACE inhibitors and digoxin morbidity
      and mortality in heart failure remain high and might respond favorably to an
      additional vasodilator. METHODS AND RESULTS: Male patients (n=450) with chronic
      heart failure (cardiac dysfunction and impaired exercise performance) on optimal
      current therapy (97% enalapril, 89% diuretics) were randomly assigned to double
      blind treatment with felodipine extended release (5 mg BID) or placebo for 3 to
      39 months (average, 18 months). Felodipine significantly reduced blood pressure
      and, at 3 months, increased ejection fraction (2.1% versus -0.1% units in the
      placebo group, P=.001) and reduced plasma atrial natriuretic peptide levels (-2.9
      versus 26.9 pg/mL in the placebo group, P=.01) but did not improve exercise
      tolerance, quality of life, or the need for hospitalization. During long-term
      follow-up, the favorable effects on ejection fraction and atrial peptide did not
      persist, but felodipine prevented worsening exercise tolerance and quality of
      life. In the felodipine and placebo groups, mortality (13.8% versus 12.8%,
      respectively) and hospitalization (43% versus 42%) rates were similar, and a
      higher incidence of peripheral edema was the only apparent side effect of
      felodipine therapy. CONCLUSIONS: Felodipine exerts a well-tolerated additional
      sustained vasodilator effect in patients with heart failure treated with
      enalapril, but the only possible long-term benefit was a trend for better
      exercise tolerance and less depression of quality of life in the second year of
      treatment. The drug appears to be safe but not clearly efficacious in patients
      with heart failure.

PMID- 9264494
TI  - Comparative effects of enalapril and verapamil on myocardial blood flow in
      systemic hypertension.
AB  - BACKGROUND: The comparative effects of calcium channel blockers and ACE
      inhibitors on myocardial blood flow (MBF) in hypertensive patients after long
      term treatment are still unknown. METHODS AND RESULTS: Twenty hypertensive
      subjects with normal coronary arteries were randomly assigned to verapamil 240 to
      480 mg/d or enalapril 10 to 40 mg/d. MBF was quantified at rest, during pacing
      tachycardia, and after dipyridamole by positron emission tomography and 13N
      ammonia before and 6 months after treatment after 1 week of pharmacological
      washout. In both groups, blood pressure and heart rate during flow measurements
      were not different before and after therapy. Before treatment, mean MBF at rest,
      during pacing tachycardia, and after dipyridamole infusion was similar in the two
      groups; however, pacing and dipyridamole flows were significantly lower than
      those obtained in a control group of normotensive subjects. After treatment, in
      the enalapril-treated patients, MBF did not change in the three study conditions.
      In the verapamil-treated patients, MBF did not change at rest and significantly
      increased during pacing and after dipyridamole. The inhomogeneity of regional MBF
      distribution, evaluated from the coefficient of variation, decreased at rest
      after both treatments and, in the enalapril group, also during pacing. No
      relation was found between changes in MBF and changes in left ventricular mass.
      CONCLUSIONS: In arterial hypertension, MBF during pacing tachycardia and after
      dipyridamole is impaired. Successful therapy with verapamil increases MBF
      response to these stimuli, independent of changes in perfusion pressure and left
      ventricular mass. These results suggest that verapamil directly improves coronary
      microcirculatory function in hypertension. Enalapril does not significantly
      change MBF but reduces the inhomogeneity of regional flow distribution.

PMID- 9264495
TI  - Overexpression of transforming growth factor-beta1 and insulin-like growth factor
      I in patients with idiopathic hypertrophic cardiomyopathy.
AB  - BACKGROUND: Idiopathic hypertrophic cardiomyopathy (HCM) is characterized by
      regional myocardial hypertrophy. To investigate involvement of growth factors on
      myocardial hypertrophy in HCM patients, we evaluated gene expression and cellular
      localization of transforming growth factor-beta1 (TGF-beta1), insulin-like growth
      factors (IGF-I and IGF-II), and platelet-derived growth factor-B (PDGF-B) in
      ventricular biopsies obtained from patients with HCM (n=8), aortic stenosis (AS)
      (n=8), or stable angina (SA) (n=8) and from explanted hearts with ischemic
      cardiomyopathy (TM) (n=7). METHODS AND RESULTS: Levels of TGF-beta1, IGF-I, IGF
      II, and PDGF-B transcripts were quantified with the use of multiplex RT-PCR.
      Glyceraldehyde 3-phosphate dehydrogenase was used as an internal standard.
      Antibodies against TGF-beta and IGF-I were used to localize their peptides within
      the myocardium. Antisense and sense (control) cRNA probes of TGF-beta1 and IGF-I,
      labeled with digoxigenin, were used to localize the growth factor transcripts by
      in situ hybridization. mRNA levels (densitometric ratio of growth
      factor/glyceraldehyde-3-phosphate dehydrogenase) of TGF-beta1 and IGF-I in HCM
      (0.75+/-0.05 and 0.85+/-0.15, respectively; mean+/-1 SEM) were significantly
      (P<.01 for all groups) elevated in comparison with non-HCM myocardium (AS: 0.38+/
      0.07, 0.29+/-0.06; SA: 0.32+/-0.04, 0.18+/-0.05; TM: 0.25+/-0.03, 0.15+/-0.03).
      mRNA levels of TGF-beta1 and IGF-I in the hypertrophic AS myocardium were greater
      (P=.02, P=.05) than those in the explanted myocardium (TM). Immunohistochemical
      and in situ hybridization studies showed increased expression of TGF-beta1 and
      IGF-I in the HCM cardiomyocytes. CONCLUSIONS: Gene expression of TGF-beta1 and
      IGF-I was enhanced in idiopathic hypertrophic cardiomyopathy and may be
      associated with its development.

PMID- 9264497
TI  - Inhibition of red cell aggregation prevents spontaneous echocardiographic
      contrast formation in human blood.
AB  - BACKGROUND: Spontaneous echocardiographic contrast (SEC) is a pattern of blood
      echogenicity that has been attributed to ultrasonic backscatter from blood cell
      aggregates that form under low shear conditions. Patients with left atrial SEC
      have an increased thromboembolic risk. This study examined the role of red cell
      and platelet aggregates in the pathogenesis of SEC in human blood and the effects
      on SEC of antithrombotic therapy and red cell disaggregatory agents. METHODS AND
      RESULTS: Blood echogenicity was examined with the use of quantitative
      videodensitometry over a controlled range of flow velocities in an in vitro model
      characterized by nonlaminar flow conditions. One hundred ninety study samples
      were prepared from single fresh blood donations (40 to 120 mL) from 24 healthy
      volunteers and 11 patients. Whole blood echogenicity was unaltered by depletion
      of platelets, stimulation of platelet aggregation with adenosine diphosphate, or
      inhibition of platelet aggregation with aspirin. Low flow-related echogenicity
      increased with increasing hematocrit (P<.001) but was abolished when red cells
      were lysed selectively with saponin (P<.001). In the presence of red cells, low
      flow-related echogenicity increased with increasing fibrinogen concentration
      (P<.001) and with plasma paraproteins. Low flow-related echogenicity in whole
      blood was unaltered by heparin and warfarin but was reduced in a dose-dependent
      manner by dextran 40 (40 mg/mL, 70% reduction, P<.001) and poloxamer 188 (8
      mg/mL, 47% reduction, P<.001), which inhibited red cell aggregation. CONCLUSIONS:
      These results support protein-mediated red cell aggregation as the mechanism of
      SEC in human blood. Inhibition of red cell aggregation, indexed by resolution of
      SEC, may provide an alternative to anticoagulant and antiplatelet therapy to
      reduce cardiac thromboembolic risk.

PMID- 9264496
TI  - Association between thrombolytic treatment and the prognosis of hemodynamically
      stable patients with major pulmonary embolism: results of a multicenter registry.
AB  - BACKGROUND: Thrombolytic treatment has been shown to accelerate resolution of
      major pulmonary embolism and lead to a rapid improvement of right-side
      hemodynamics. However, the association between these favorable effects and the
      clinical outcome of patients who have no severe hemodynamic compromise at
      presentation remains unknown. METHODS AND RESULTS: The present multicenter
      registry included 719 consecutive patients with major pulmonary embolism
      according to clinical, echocardiographic, scintigraphic, and cardiac
      catheterization criteria. Symptom onset was acute (<48 hours) in 63% of patients.
      All patients were hemodynamically stable (ie, without evidence of cardiogenic
      shock) at presentation. Primary thrombolytic treatment (within 24 hours of
      diagnosis) was given to 169 patients (23.5%), whereas the remaining 550 patients
      were initially treated with heparin alone. Overall 30-day mortality was
      significantly lower in the patients who received thrombolytic agents (4.7 versus
      11.1%, P=.016). Clinical factors associated with a higher death rate were syncope
      (P=.012), arterial hypotension (P=.021), history of congestive heart failure
      (P=.013), and chronic pulmonary disease (P=.032). However, only primary
      thrombolysis was found by multivariate analysis to be an independent predictor of
      survival (odds ratio for in-hospital death, 0.46; 95% confidence interval, 0.21
      to 1.00). Patients who underwent early thrombolytic treatment had a reduced rate
      of recurrent pulmonary embolism (7.7 versus 18.7%, P<.001) but also a higher
      frequency of major bleeding episodes (21.9% versus 7.8%, P<.001). Cerebral
      bleeding occurred in 2 patients in each treatment group, and 1 patient in each
      group died of a bleeding complication. CONCLUSIONS: The results of our study
      suggest that thrombolysis may favorably affect the clinical outcome of
      hemodynamically stable patients with major pulmonary embolism.

PMID- 9264498
TI  - Association of cigarette smoking with chronotropic incompetence and prognosis in
      the Framingham Heart Study.
AB  - BACKGROUND: In this study, we sought to determine whether cigarette smoking is
      associated with chronotropic incompetence and to explore prognostic implications
      of this association. METHODS AND RESULTS: Members of the Framingham Offspring
      Study (1468 men and 1642 women) underwent graded exercise. Chronotropic
      incompetence was assessed in two ways: (1) failure to achieve an age-predicted
      target heart rate and (2) a low chronotropic index, a heart rate response measure
      that accounts for effects of age, resting heart rate, and physical fitness.
      Smokers were more likely to fail to reach target heart rate than were nonsmokers
      (men, 25% versus 15%, odds ratio [OR], 1.97; 95% confidence interval [CI], 1.51
      to 2.56; women, 32% versus 18%; OR, 2.10; 95% CI, 1.63 to 2.61) and were more
      likely to have a low chronotropic index (men, 17% versus 12%; OR, 1.50; 95% CI,
      1.12 to 2.03; women, 17% versus 8%; OR, 2.28; 95% CI, 1.68 to 3.09). These
      associations persisted after adjustment for age, cardiovascular risk factors,
      pulmonary function, and ST-segment response to graded exercise. During 8 years of
      follow-up, there were 48 deaths and 90 incident coronary heart disease events
      among the men. After adjustment for the same confounders, men who were smokers
      and failed to achieve target heart rate were at particularly high risk for death
      (adjusted relative risk [RR], 2.45; 95% CI, 1.14 to 5.24) and for coronary heart
      disease (adjusted RR, 4.92; 95% CI, 2.84 to 8.53). There were too few end points
      in women for analysis. CONCLUSIONS: In this population-based cohort, cigarette
      smoking was predictive of chronotropic incompetence. Male smokers who manifested
      chronotropic incompetence were at particularly high risk for death and coronary
      heart disease events.

PMID- 9264499
TI  - Value of QT dispersion in the interpretation of exercise stress test in women.
AB  - BACKGROUND: Exercise testing in women is associated with a high incidence of
      false-positive ECG changes and should be combined with an imaging study. The QT
      dispersion (QTD), recorded as the difference between maximum and minimum QT
      intervals on a 12-lead ECG, is sensitive to myocardial ischemia and may improve
      the accuracy of exercise testing in women. METHODS AND RESULTS: Exercise ECGs
      were analyzed in 64 women who had undergone exercise ECG and coronary angiography
      for clinical indications: 20 patients with normal exercise stress test and
      nonsignificant (< or = 50% diameter narrowing of a major epicardial coronary
      artery) coronary artery disease (CAD) on angiography (true-negative; TN group),
      20 patients with positive exercise stress tests (> or = 1 mm ST-segment
      depression or reversible perfusion defects) and significant CAD (true-positive;
      TP group), and 24 patients with positive exercise stress tests but no significant
      CAD (false-positive; FP group). The exercise QTD was 45+/-15 ms in TN, 80+/-23 ms
      in TP (P<.0001 versus TP), and 41+/-14 ms in FP (P=NS versus TN and <.0001 versus
      TP) groups. A stress QTD of > 60 ms had a sensitivity of 70% and specificity of
      95% for the diagnosis of significant CAD compared with 55% (P<.05) and 63%
      (P<.01), respectively, for > or = 1 mm ST-segment depression during stress. When
      QTD of > 60 ms was added to ST-segment depression as a condition for positive
      test, the specificity increased to 100%. CONCLUSIONS: Exercise QTD is an easily
      measurable ECG variable that significantly increases the accuracy of exercise
      testing in women.

PMID- 9264501
TI  - Novel low-molecular-weight inhibitor of PAI-1 (XR5118) promotes endogenous
      fibrinolysis and reduces postthrombolysis thrombus growth in rabbits.
AB  - BACKGROUND: Elevated levels of plasminogen activator inhibitor 1 (PAI-1) have
      been associated with the occurrence of thrombotic disease, and inhibition of PAI
      1 activity in vivo resulted in enhanced thrombolysis and a reduction in
      reocclusion. Besides monoclonal antibodies and peptides, no suitable agents that
      are able to block PAI-1 activity are available to date. The present study was
      designed to test the interaction between a nonantibody, nonpeptide,
      diketopiperazine-based inhibitor of PAI-1, XR5118, and PAI-1 and to assess the
      effect of XR5118 on PAI-1 activity in vitro and on in vivo thrombolysis and
      thrombus growth in an experimental thrombosis model in rabbits. METHODS AND
      RESULTS: The binding site of XR5118 on the PAI-1 molecule was studied by
      competitive binding experiments with mapped anti-PAI-1 monoclonal antibodies by
      use of surface plasmon resonance experiments. XR5118 selectively and
      competitively inhibited binding of the PAl-1-inhibiting monoclonal antibody CLB
      2C8, indicating that binding of XR5118 to PAI-1 takes place at the area between
      amino acids 110 and 145 of the PAI-1 molecule, which is known to be involved with
      the binding of PAI-1 to tissue plasminogen activator (TPA). Incubation of plasma
      or platelet releasate with XR5118 resulted in a dose-dependent inhibition of PAI
      1 activity. Systemic infusion of XR5118 induced a significant reduction in plasma
      PAI-1 activity levels from 23.7+/-4.9 to 10.9+/-3.4 IU/mL. Administration of
      XR5118 resulted in a significant, twofold increase in endogenous thrombolysis
      compared with the control. Thrombus growth in rabbits receiving both XR5118 and
      rTPA was significantly attenuated compared with rabbits receiving rTPA alone
      (13.5+/-2.7% versus 19.9+/-3.8%, respectively). CONCLUSIONS: XR5118 binds to PAI
      1 and reduces plasma PAI-1 activity levels. Furthermore, XR5118 promotes
      endogenous thrombolysis and inhibits thrombus accretion and is the first
      nonpeptide compound with significant anti-PAI-1 activity in vivo in these models.

PMID- 9264500
TI  - ACE inhibition: postsynaptic adrenergic sympatholytic action in men.
AB  - BACKGROUND: The mechanisms by which ACE inhibitors produce a sustained clinical
      benefit are not entirely clear but may involve the sympathetic nervous system. We
      compared the effect of local brachial artery infusions of an ACE inhibitor
      (perindoprilat) with the effect of placebo (0.9% NaCl) on endogenously mediated
      (lower body negative pressure [LBNP]) and exogenously mediated (brachial artery
      infusions of norepinephrine) sympathetic vasoconstriction. METHODS AND RESULTS:
      Eight healthy, normotensive male volunteers (20 to 32 years) were studied on one
      occasion. Forearm blood flow (FABF; mL x dL forearm(-1) x min(-1)) responses to
      LBNP (-20 cm H2O) and increasing increments of norepinephrine (60, 120, and 240
      pmol/min) were compared when coinfused with placebo and perindoprilat (5
      nmol/mL). FABF was measured simultaneously in both arms by venous occlusion
      plethysmography with mercury-in-Silastic strain gauges with drugs infused locally
      at the left brachial artery. The right arm served as a control. Baseline FABFs
      did not differ between the infused and control arms (3.04+/-0.52 versus 3.05+/
      0.42 mL x dL forearm(-1) x min(-1); P=.98). Perindoprilat did not alter FABF when
      infused alone, but the FABF response to LBNP in the infused arm was attenuated
      during the perindoprilat infusion compared with placebo (-17.8+/-4.3% versus 
      33.8+/-3.1%, respectively; P=.015). The FABF response to the maximum dose of
      norepinephrine was also attenuated during the perindoprilat infusion compared
      with placebo (-28.3+/-1.4% versus -36.9+/-2.8%, respectively; P=.015). The mean
      slope of the FABF (log transformed) versus norepinephrine dose-response curve was
      significantly attenuated by perindoprilat compared with placebo (-0.11+/-0.019
      versus -0.02+/-0.02; P=.001). CONCLUSIONS: We conclude that ACE inhibition has a
      significant postsynaptic sympatholytic effect in the forearm circulation of men.

PMID- 9264502
TI  - Increase in angiotensin II type 1 receptor expression immediately after ischemia
      reperfusion in isolated rat hearts.
AB  - BACKGROUND: Myocardial ischemia is known to upregulate the systemic renin
      angiotensin system, which influences myocardial ischemic events by affecting
      hemodynamics and hemostatic activity. This study was designed to examine whether
      angiotensin II (Ang II) receptor expression in the myocardium is altered
      immediately after ischemia-reperfusion. METHODS AND RESULTS: Isolated buffer
      perfused Sprague-Dawley rat hearts were subjected to continuous perfusion
      (control, n=5) or to 25 minutes of global ischemia followed by 30 minutes of
      reperfusion (n=10). Autoradiographic analysis for Ang II receptors of multiple
      myocardial sections was performed. Whereas continuous perfusion of hearts
      resulted in minor changes in coronary perfusion pressure (CPP), left ventricular
      end-diastolic pressure (LVEDP), and developed left ventricular pressure
      (dLVP=LVSP-LVEDP), ischemia-reperfusion caused a marked increase in CPP and LVEDP
      and a decrease in dLVP, indicating severe cardiac dysfunction. Concurrently,
      total myocardial Ang II receptor expression was greater (P<.05) in hearts
      subjected to ischemia-reperfusion than in the continuously perfused control
      hearts. Most of the increase in Ang II receptor expression was due to an increase
      in type 1 receptor (AT1) expression (34.6+/-6.5 versus 18.2+/-4.4 fmol/g, P<.05),
      because Ang II type 2 receptor expression was unaffected. To examine the
      importance of AT1 receptor expression, another group of isolated rat hearts (n=5)
      was perfused with buffer containing losartan (10(-5) mol/L) and subjected to
      ischemia followed by reperfusion. Perfusion of hearts with losartan attenuated
      the ischemia-reperfusion-induced cardiac dysfunction. Perfusion of hearts with
      losartan also blocked the ischemia-reperfusion-induced increase in myocardial AT1
      binding. CONCLUSIONS: These observations indicate that myocardial AT1 expression
      increases immediately after ischemia-reperfusion and contributes to cardiac
      dysfunction.

PMID- 9264503
TI  - Estrogen effects on insulin-like growth factor-I (IGF-I)-induced cell
      proliferation and IGF-I expression in native and allograft vessels.
AB  - BACKGROUND: Estrogen protects against cardiovascular disease in both patients and
      animal models and regulates insulin-like growth factor-I (IGF-I), an important
      cell-cycle progression factor. METHODS AND RESULTS: Smooth muscle cells and
      tissues were harvested from male recipient rabbits that 6 weeks earlier had
      received a cardiac allograft transplant consisting of a donor heart and ascending
      aorta. Segments of the ascending aorta from the native and allograft hearts from
      9 placebo-treated and 8 estradiol-treated recipients were compared by using IGF-I
      stimulated [3H]thymidine incorporation. The responses of the native vessel
      segments were similar (175.3+/-32% and 166.9+/-41%, respectively; P>.05) whether
      or not the recipients had been treated for 6 weeks with estradiol. In the grafts,
      however, estradiol markedly inhibited vascular cell thymidine incorporation
      (328.04+/-56% compared with 67.3+/-11%; P<.02). Smooth muscle cells were derived
      from the native aorta of the placebo-treated rabbits to study the effect of
      estradiol in vitro. IGF-I increased cell counts in a concentration-dependent
      manner. In serum-starved cells estradiol further decreased cell proliferation;
      this effect was blocked by the specific estrogen receptor antagonist ZK-119.010.
      Immunohistochemistry staining for IGF-I protein in the coronary arteries and
      ascending aorta of the cardiac allograft from the placebo-treated recipients
      revealed extensive IGF-I expression in the myointima. In contrast, IGF-I protein
      was not expressed in the coronary arteries and ascending aorta of the cardiac
      allograft from the estradiol-treated recipients. The IGF-I protein was
      extensively expressed only in the placebo-treated graft vessels. Myointimal
      thickening of the coronary arteries was significantly reduced by estradiol
      treatment (17.9+/-1.5% versus 44.3+/-3.7%; P<.02). CONCLUSIONS: In vivo estradiol
      treatment abolishes both IGF-I mitogenic effects and IGF-I protein expression in
      the vascular wall, which may be causally related to the inhibitory effect of
      estradiol on transplant arteriosclerosis.

PMID- 9264504
TI  - Nitric oxide regulates monocyte chemotactic protein-1.
AB  - BACKGROUND: Monocyte chemotactic protein-1 (MCP-1) is a 76-amino-acid chemokine
      thought to be the major chemotactic factor for monocytes. We and others have
      demonstrated that NO inhibits monocyte-endothelial cell interactions and
      atherogenesis. We hypothesize that the antiatherogenic effect of NO may be due in
      part to its inhibition of MCP-1 expression. METHODS AND RESULTS: Smooth muscle
      cells (SMCs) were isolated from normal rabbit aortas by the explant method. Cells
      were then exposed to LPS (10 microg/mL), native LDL, or oxidized LDL (30
      microg/mL) for 6 hours. The expression of MCP-1 in SMCs and chemotactic activity
      in the conditioned medium were induced by lipopolysaccharide (LPS) or by oxidized
      LDL but not native LDL. The induction of MCP-1 by cytokines or oxidized
      lipoproteins was associated with an increased generation of superoxide anion by
      the SMCs and increased activity of the transcriptional protein nuclear factor
      kappaB (NFkappaB). The induced expression of MCP-1 and activation of NFkappaB
      were reduced by previous exposure of the SMCs to the NO donor DETA-NONOate (100
      micromol/L) (P<.05). To determine whether NO exerted its effect at a
      transcriptional level, SMCs and COS cells were transfected with a 400-bp fragment
      of the MCP-1 promoter. Promoter activity was enhanced by oxidized LDL, and LPS
      was inhibited by DETA-NO. Nuclear run-on assays confirmed that the effect of NO
      occurred at a transcriptional level. To investigate the role of endogenous NO in
      the regulation of MCP-1 in vivo, New Zealand White rabbits were fed normal chow,
      normal chow plus nitro-L-arginine (LNA), high-cholesterol diet (Chol), or high
      cholesterol diet supplemented with L-arginine (Arg). After 2 weeks, thoracic
      aortas were harvested and total RNA was isolated. Northern analysis using full
      length MCP-1 cDNA demonstrated increased expression in Chol and LNA aortas; this
      expression was decreased in aortas from Arg animals. CONCLUSIONS: These studies
      indicate that the antiatherogenic effect of NO may be mediated in part by its
      inhibition of MCP-1 expression.

PMID- 9264505
TI  - Reduction in stent and vascular graft thrombosis and enhancement of thrombolysis
      by recombinant Lys-plasminogen in nonhuman primates.
AB  - BACKGROUND: To enhance thrombolytic responses without increasing hemorrhagic
      risks, the antithrombotic effects of recombinant Lys-plasminogen (r-LysPgn), a
      prothrombolytic plasminogen intermediate, were examined in baboon models of
      thrombus formation and dissolution. METHODS AND RESULTS: The dose-response
      effects of r-LysPgn, alone or in combination with subthreshold dosing of tissue
      plasminogen activator (TPA), were measured with respect to the accumulation of
      (111)In-labeled platelets and (125)I-fibrin in thrombus forming on endovascular
      metallic stents or thrombogenic segments of vascular graft interposed in
      exteriorized long-term arteriovenous (AV) femoral shunts. Thrombolytic losses
      have also been determined for preformed, stable, (111)In-platelet- and (125)I
      fibrin-labeled graft thrombus and corresponding propagated thrombotic tails,
      together with changes in blood tests of thrombosis, thrombolysis, and hemostasis.
      Bolus intravenous r-LysPgn in escalating doses (2, 4, or 8 mg/kg) increased
      circulating plasminogen levels in a dose-dependent manner, was removed by log
      linear clearance with a T50 of 120 minutes, and reciprocally decreased the
      accumulating thrombus on metallic stents and segments of vascular graft (P<.001
      in all cases for 8-mg/kg doses). r-LysPgn also impaired platelet aggregatory
      responses to physiological agonists in vitro but not ex vivo. Prethrombosis
      administration of low-dose r-LysPgn (2 mg/kg) greatly enhanced the lysis of
      radiolabeled nonoccluding thrombus by a subthreshold dose of TPA (0.1 mg/kg)
      compared with TPA-only controls (P=.03). CONCLUSIONS: Elective bolus injections
      of r-LysPgn before stent deployment decrease the amount of thrombus formed
      without compromising hemostasis by facilitating endogenous TPA thrombolysis. r
      LysPgn may provide effective and safe antithrombotic therapy for interventional
      vascular procedures.

PMID- 9264506
TI  - Nonpeptide glycoprotein IIb/IIIa inhibitors: 14: oral antithrombotic efficacy of
      L-738,167 in a conscious canine model of coronary artery electrolytic injury.
AB  - BACKGROUND: A conscious dog model of left circumflex coronary artery electrolytic
      injury was used to assess the oral antithrombotic efficacy of L-738,167, a potent
      nonpeptide antagonist of platelet GP IIb/IIIa. L-738,167 was administered either
      as a single oral pretreatment dose 2 hours before initiation of vessel injury or
      as two oral doses administered 24 hours apart, 12 hours before and after
      initiation of vessel injury. METHODS AND RESULTS: In untreated controls,
      electrolytic coronary injury (50 microA, 3 hours) resulted in thrombotic
      occlusion and myocardial ischemia in 15 of 16 dogs, with 4 developing lethal
      arrhythmias. Significant reductions in thrombus mass and complete prevention of
      myocardial ischemia and infarction were achieved with a single 100- to 300
      microg/kg dose of L-738,167 pretreatment and with two 100-microg/kg doses
      administered 12 hours before and after initiation of vessel injury. Delays and/or
      reductions in incidence of ischemia, thrombus mass, and infarct sizes also were
      achieved with 10- to 30-microg/kg pretreatment and with two 30-microg/kg doses
      administered 12 hours before and after initiation of vessel injury. None of the L
      738,167-treated animals developed lethal arrhythmias. A single oral 100-microg/kg
      dose of L-738,167 achieved >90% inhibitions of ADP (extent)- and collagen (rate)
      induced ex vivo platelet aggregation and fivefold to sixfold or greater
      elevations in bleeding time; a single oral 30-microg/kg dose of L-738,167
      achieved sustained 40% to 70% inhibitions of ADP- and collagen-induced ex vivo
      platelet aggregation and modest twofold to threefold elevations in bleeding time.
      At 12 to 24 hours after single oral 30- and 100-microg/kg doses of L-738,167, a
      substantially greater L-738,167 concentration was associated with platelets than
      free in plasma. CONCLUSIONS: These findings are indicative of potent and
      sustained oral antithrombotic efficacy and suggest that L-738,167 possesses
      potential for the oral management of chronic thrombotic occlusive disorders.

PMID- 9264507
TI  - Myocardial perfusion imaging in the setting of coronary artery stenosis and acute
      myocardial infarction using venous injection of a second-generation
      echocardiographic contrast agent.
AB  - BACKGROUND: We hypothesized that by producing excellent myocardial opacification,
      venous injection of FS-069 coupled with intermittent harmonic imaging (IHI) can
      be used to determine the presence and severity of coronary stenoses during
      hyperemia, the size of the risk area during coronary occlusion, and the extent of
      myocardial salvage after reperfusion. METHODS AND RESULTS: Twelve dogs were
      imaged both continuously and intermittently (every end systole) in the
      fundamental (2 MHz) and harmonic (transmit at 2 and receive at 4 MHz) modes. FS
      069 (1 mL) was injected intravenously for all stages and modes of imaging.
      Myocardial video intensity was severalfold (P<.01) higher during IHI than all
      other modes of imaging. Perfusion defects were difficult to measure during
      continuous and intermittent fundamental imaging and during continuous harmonic
      imaging. In comparison, the defects were clearly demarcated during IHI. When this
      mode was used, the magnitude of perfusion mismatch during hyperemia in the
      presence of a coronary stenosis correlated closely with the magnitude of flow
      mismatch when radiolabeled microspheres were used (r=.94). The perfusion defect
      sizes during coronary occlusion and reperfusion also correlated closely with
      postmortem risk area (r=.89) and infarct size (r=.96), respectively. CONCLUSIONS:
      Venous injection of FS-069 coupled with IHI produces excellent myocardial
      opacification. This approach can be used to determine the severity of coronary
      stenoses during hyperemia, the size of the risk area during coronary occlusion,
      and the extent of myocardial salvage after reperfusion. This approach, therefore,
      holds promise in the clinical setting.

PMID- 9264508
TI  - Both dietary fish-oil supplementation and aspirin fail to inhibit atherosclerosis
      in long-term vein bypass grafts in moderately hypercholesterolemic nonhuman
      primates.
AB  - BACKGROUND: Aortocoronary vein bypass grafts are vulnerable to late
      atherosclerotic occlusion. Conventional platelet inhibitor therapy provides early
      but not persistent protection against graft failure. Evidence suggests that
      consumption of marine foods may reduce cardiovascular disease, possibly because
      of the unique long-chain unsaturated omega-3 fatty acids present in these foods.
      We hypothesized that dietary fish-oil supplementation would protect against
      atherosclerosis in vein bypass grafts. METHODS AND RESULTS: Thirty-three
      moderately hypercholesterolemic cynomolgus macaques were divided into four
      groups: control, control+aspirin, fish oil, and fish oil+aspirin. Each control
      group received olive oil as placebo to equalize calorie and fat consumption with
      that of the fish-oil groups. Both oils were in ethyl ester form, with the fish
      oil providing 0.88 g/d eicosapentaenoic acid. The aspirin dose was 40 mg/d.
      Cephalic vein grafts were interposed bilaterally in the carotid arteries and
      excised for analysis at 4 years. Bleeding time was significantly prolonged in all
      groups receiving fish oil or aspirin (P<.05). Plasma cholesterol levels were
      similar among groups, averaging 6.9+/-2.4 mmol/L (267+/-94 mg/dL). The extent of
      atherosclerosis in vein grafts did not differ among groups as evaluated both by
      Sudan IV staining of intimal lipid lesions (27+/-21% of total surface area,
      P=.89) and analysis of cholesterol content (236+/-203 nmol/mg, 9.1+/-7.8
      microg/mg, P=.85). Vein graft connective tissue composition was also unaffected
      by treatment. CONCLUSIONS: Our findings do not support the use of concentrated
      dietary fish-oil supplements or aspirin for the prevention of atherosclerosis in
      long-term vein bypass grafts. Consumption of fish flesh or less refined oil
      preparations could have effects different from those of the purified fish-oil
      ethyl esters we used.

PMID- 9264509
TI  - Role of preischemic glycogen depletion in the improvement of postischemic
      metabolic and contractile recovery of ischemia-preconditioned rat hearts.
AB  - BACKGROUND: Ischemic preconditioning (IPC) attenuates acidosis during prolonged
      ischemia and improves contractile and metabolic parameters during subsequent
      reperfusion. Glycogen depletion induced by IPC is proposed as a potential
      mechanism. METHODS AND RESULTS: We studied the influence of manipulations of
      preischemic glycogen levels (Pre-G, micromol glucose/g wet wt) on contractile and
      metabolic (via 31P-nuclear magnetic resonance) parameters during 30 minutes of
      ischemia and recovery in four groups of isovolumic rat hearts: First, control
      (Con, n=18, mean Pre-G, 21.5+/-0.8); second, after two 5-minute IPC periods (IPC,
      n=12, Pre-G, 11.3+/-0.7); third, a control group in which Pre-G was depleted by
      glucose-free, acetate perfusion (Con-LowG, n=9, Pre-G, 7.9+/-1.2); and fourth, an
      IPC group in which Pre-G was raised by glucose and lactate perfusion such that
      Pre-G was similar to Con (IPC-HiG, n=11, Pre-G, 20+/-1.4). Manipulation of Pre-G
      significantly altered the pH fall during 30 minutes of ischemia (Con, 5.76+/-.03,
      Con-LowG, 6.26+/-.07; IPC-HiG, 5.91+/-.02, IPC, 6.05+/-.09). IPC-HiG hearts had
      significantly worse metabolic recovery (PCr, 70+/-7 versus 91+/-3% initial; IPC
      HiG versus IPC, P<.05) and contractile recovery (end-diastolic pressure, 52+/-5
      versus 29+/-5 mm Hg, P<.05) than IPC hearts but better recovery than Con (%PCr,
      56+/-6% and end-diastolic pressure, 72+/-6 mm Hg). An ischemic rise in
      intracellular magnesium occurred and was atttenuated in preconditioned hearts.
      CONCLUSIONS: Pre-G levels before ischemia influence but are not the sole
      determinants of the extent of acidosis during prolonged ischemia and of metabolic
      and contractile recovery during reperfusion in control and preconditioned hearts.

PMID- 9264510
TI  - Ischemic preconditioning: differences in protection and susceptibility to
      blockade with single-cycle versus multicycle transient ischemia.
AB  - BACKGROUND: We compared ischemic preconditioning (IP) induced with a single cycle
      of transient ischemia and reperfusion with that induced by multiple cycles in
      terms of (1) efficacy of protection against myocardial necrosis and (2)
      susceptibility to pharmacological blockade by inhibition of protein kinase C
      (PKC) or elevation of cAMP. METHODS AND RESULTS: All rabbits were subjected to 30
      minutes of regional ischemia and 90 minutes of reperfusion in vivo. IP was
      induced with either one or three cycles of 5-minute transient ischemia and 10
      minute reperfusion given before the 30-minute ischemia. Drug-treated hearts
      received a bolus dose of one of the following just before the 30-minute ischemia:
      (1) the PKC inhibitor chelerythrine (3.8 mg/kg), (2) the PKC inhibitor polymyxin
      B (10 mg/kg), or (3) the cAMP-increasing agent NKH477 (45 microg/kg). IP induced
      with either one or three cycles of transient ischemia and reperfusion
      significantly protected the heart against infarction, although the extent of
      protection was significantly greater with three-cycle IP. Chelerythrine,
      polymyxin B, or NKH477 alone did not alter infarct size in control hearts, nor
      did they increase infarct size in hearts preconditioned with three-cycle IP. In
      contrast, when IP was induced with only a single cycle, all three of these drugs
      significantly increased infarct size above that of the untreated one-cycle IP
      group. However, infarct size in all three of these drug-treated one-cycle IP
      groups was still significantly lower than that in the corresponding drug-treated
      controls, indicating a partial block of IP. CONCLUSIONS: Three-cycle IP provided
      more effective protection against myocardial necrosis than one-cycle IP and was
      less susceptible to blockade by inhibitors of PKC or an agent that increases cAMP
      levels. However, single-cycle IP was only partially blocked by either inhibition
      of PKC or stimulation of cAMP production. Neither activation of the PKC pathway
      nor reduced formation of cAMP alone fully accounted for the necrosis protection
      by IP even when induced with only a single cycle of transient ischemia.

PMID- 9264511
TI  - Arterial remodeling after balloon angioplasty or stenting in an atherosclerotic
      experimental model.
AB  - BACKGROUND: Recent studies have indicated that coronary restenosis after balloon
      angioplasty is the sum of geometric remodeling and neointimal formation. A
      proportional relationship between acute gain and late lumen loss has been
      observed in clinical trials. The aims of this study were to evaluate (1) the
      contribution of geometric remodeling and neointimal formation to the proportional
      gain-loss relationship after PTA or stenting and (2) the relationship between
      geometric remodeling and neointimal formation. METHODS AND RESULTS: In
      atherosclerotic iliac arteries of 29 Yucatan micropigs, PTA or stenting was
      performed, with serial intravascular ultrasound (IVUS) and quantitative
      angiography before and after intervention and at 2 or 42 days of follow-up,
      followed by histomorphometrical analysis. For PTA at 42 days, late lumen loss by
      IVUS correlated strongly with geometric remodeling, expressed as late media
      bounded area (MBA) loss (R2=.843, P<.001, n=20), and correlated weakly with
      intimal hyperplasia area (R2=.214, P=.02). For stented arteries, however, late
      lumen loss correlated moderately with intimal hyperplasia (R2=.367, P=.01, n=18)
      and only weakly with geometric remodeling (R2=.195, P=.04). Late lumen loss and
      late MBA loss of reference segments were observed at 42 days, especially in PTA
      arteries. Intimal hyperplasia and geometric remodeling were not correlated.
      CONCLUSIONS: In this experimental model, the proportional relationship between
      acute gain and late lumen loss is mainly due to the proportional relationship
      between acute gain and geometric remodeling for PTA and between acute gain and
      intimal hyperplasia for stents. Finally, neointimal formation and remodeling seem
      to be unrelated processes.

PMID- 9264512
TI  - Myocardial contrast echocardiography can be used to quantify intramyocardial
      blood volume: new insights into structural mechanisms of coronary autoregulation.
AB  - BACKGROUND: Changes in intramyocardial blood volume (IBV) mediate autoregulatory
      adaptations to coronary stenosis. This study investigated whether (1) myocardial
      contrast echocardiography (MCE) can quantify changes in IBV during coronary
      stenosis and (2) the relation between coronary resistance- and MCE-derived IBV
      could yield insight into structural mechanisms of IBV change. METHODS AND
      RESULTS: A circulating in vitro model with constant flow and varying volume was
      used to determine whether indicator dilution theory could be applied to MCE.
      Contrast echo was performed with albumin microbubbles, and time-intensity data
      were fit to a gamma-variate function. With six different volumes, bubble transit
      time was linearly related to volume (r=.91). To determine whether changes in IBV
      could be quantified in vivo, the left anterior descending coronary artery in 12
      dogs was instrumented with a flow probe, occluder, and intracoronary pressure
      catheter, and non-flow-limiting stenoses were created. IBV was derived by use of
      coronary resistance measurements applied to models that assumed autoregulation to
      occur via vasodilatation or microvascular recruitment. MCE-IBV was calculated
      from microbubble transit rates. At constant flow, MCE and resistance IBV
      increased with stenosis. Although MCE and resistance IBV were linearly related,
      MCE overestimated IBV derived from the vasodilatation model and underestimated
      IBV calculated from the recruitment model. CONCLUSIONS: MCE can quantify
      autoregulatory increases in IBV that maintain resting myocardial perfusion. These
      data suggest that both microvessel vasodilatation and recruitment are dual
      mechanisms of IBV change. MCE thus may be a clinically useful technique for the
      detection and quantification of coronary artery disease at rest.

PMID- 9264513
TI  - Noninvasive electrocardiographic imaging: reconstruction of epicardial
      potentials, electrograms, and isochrones and localization of single and multiple
      electrocardiac events.
AB  - BACKGROUND: The goal of noninvasive electrocardiographic imaging (ECGI) is to
      determine electric activity of the heart by reconstructing maps of epicardial
      potentials, excitation times (isochrones), and electrograms from data measured on
      the body surface. METHODS AND RESULTS: Local electrocardiac events were initiated
      by pacing a dog heart in a human torso-shaped tank. Body surface potential
      measurements (384 electrodes) were used to compute epicardial potentials
      noninvasively. The accuracy of reconstructed epicardial potentials was evaluated
      by direct comparison to measured ones (134 electrodes). Protocols included pacing
      from single sites and simultaneously from two sites with various intersite
      distances. Body surface potentials showed a single minimum for both single- and
      double-site pacing (intersite distances of 52, 35, and 17 mm). Noninvasively
      reconstructed epicardial electrograms, potentials, and isochrones closely
      approximated the measured ones. Single pacing sites were reconstructed to within
      < or = 10 mm of their measured positions. Dual sites were located accurately and
      resolved for the above intersite distances. Regions of sparse and crowded
      isochrones, indicating spatial nonuniformities of epicardial activation spread,
      were also reconstructed. CONCLUSIONS: The study demonstrates that ECGI can
      reconstruct epicardial potentials, electrograms, and isochrones over the entire
      epicardial surface during the cardiac cycle. It can provide detailed information
      on local activation of the heart noninvasively. Its uses could include
      localization of cardiac electric events (eg, ectopic foci), characterization of
      nonuniformities of conduction, characterization of repolarization properties (eg,
      dispersion), and mapping of dynamically changing arrhythmias (eg, polymorphic VT)
      on a beat-by-beat basis.

PMID- 9264514
TI  - Hemodynamic effects of chronic prenatal ventricular pacing for the treatment of
      complete atrioventricular block.
AB  - BACKGROUND: Increasing the heart rate of the fetus with cardiac failure caused by
      complete AV block (CAVB) may allow delivery of a full-term, stable neonate with
      preserved ventricular function. Direct fetal pacing may be a feasible method to
      achieve this, but the effect of pacing on the structure and function of the
      rapidly developing fetal heart is unknown. METHODS AND RESULTS: CAVB was created
      in fetal lambs at 80% gestation by cryoablating the AV node. Epicardial
      ventricular pacing at 130 bpm was achieved by use of a pacemaker placed under the
      pectoral muscles. The fetus was returned to the uterus and allowed to continue to
      term. Ventricular function was assessed 1 week after birth in 7 lambs with CAVB
      and 10 control lambs. By use of the conductance catheter technique, the end
      systolic pressure-volume relationship was determined at different heart rates,
      pacing conditions, and inotropic states. The contractility was not different
      between the two groups at their baseline heart rates and rhythms or when they
      were paced synchronously compared with asynchronously. Also, both groups
      responded significantly and similarly to inotropic manipulation, indicating
      preserved contractile reserve. Finally, in both groups, increased heart rates
      were associated with increased contractility, indicating an intact force
      frequency relationship. CONCLUSIONS: We conclude that chronic epicardial
      ventricular pacing is well tolerated by the fetus, can be successfully applied as
      a treatment for CAVB, and does not adversely affect myocardial function in the
      rapidly developing, immature heart.

PMID- 9264515
TI  - Chelation therapy for peripheral arterial occlusive disease: a systematic review.

PMID- 9264516
TI  - Images in cardiovascular medicine. Constrictive pericarditis.

PMID- 9264517
TI  - Images in cardiovascular medicine. Correlative imaging of aortopulmonary window:
      demonstration with echocardiography, angiography, and MRI.

PMID- 9264518
TI  - Heart rate variability and Holter ST-segment changes after thrombolysis in acute
      myocardial infarction.

PMID- 9264519
TI  - Cardiopulmonary baroreflex control of human renal cortical blood flow.

PMID- 9264520
TI  - Recollections of Dr Lewis Dexter.

PMID- 9264521
TI  - Myocardial perfusion and TIMI flow.

PMID- 9264522
TI  - Endothelial function in patients with chest pain and normal coronary arteries.

PMID- 9264523
TI  - Nitric oxide activity at the site of coronary spasm: deficient or preserved?

PMID- 9264524
TI  - Hemodynamic effects of repetitive cocaine administration.

PMID- 9264525
TI  - ACE*D and cardiovascular disease.

PMID- 9264526
TI  - Pathophysiology of chronic myocardial hibernation.

PMID- 9264527
TI  - Coagulation in chronic atrial fibrillation.

PMID- 9264528
TI  - Coagulation in chronic atrial fibrillation.

PMID- 9264529
TI  - Task Force report on heart rate variability.

PMID- 9264530
TI  - Predictors of outcome of balloon angioplasty of native aortic coarctation.

PMID- 9264531
TI  - Prevastatin treatment in angina pectoris.

PMID- 9264532
TI  - Angiographic severity of coronary disease in patients undergoing vascular
      surgery.

PMID- 9264534
TI  - Bicycle ergometer cadence in cardiac rehabilitation.

PMID- 9264533
TI  - Long-term consequences of Kawasaki disease.

PMID- 9264535
TI  - Rising death rates from coronary artery disease.

PMID- 9264536
TI  - Myocardial infarct size limiting effect of low body temperature in rats depends
      on the duration of coronary artery occlusion.

PMID- 9264537
TI  - Peroxynitrite-mediated nitration of peptides: characterization of the products by
      electrospray and combined gas chromatography-mass spectrometry.
AB  - Peroxynitrite (ONOO-) can react with a wide range of biomolecules resulting in
      peroxidation, oxidation, and/or nitration and as a consequence cause their
      inactivation. In this study mass spectrometry (MS) combined with both liquid (LC)
      and gas chromatography (GC) has been employed to identify the products formed
      following ONOO- treatment of three peptides at physiological pH: leucine
      enkephalin (YGGFL), V3 loop (GPGRAF), and LVV-hemorphin7 (LVVYPWTQRF). LC-MS
      analysis of leucine-enkephalin following ONOO treatment indicated the formation
      of products corresponding in mass to mono- and dinitrated forms of the starting
      material. LC-MS-MS and GC-MS analyses revealed no evidence for the formation of
      nitrophenylalanine; however, both 3-nitrotyrosine and 3,5-dinitrotyrosine were
      observed and characterized. GC-MS analysis of hydrolyzed peptides following ONOO-
      treatment confirmed the presence of nitrated and dinitrated tyrosine. However,
      when a 20-fold molar excess of ONOO- was reacted with leucine-enkephalin, only
      about half of the tyrosine originally present in the peptide could be accounted
      for in the acid hydrolysate. The main product was 3-nitrotyrosine which
      represented ca. 50% of the original tyrosine; traces of 3,5-dinitrotyrosine (ca.
      3% of the original tyrosine) were also present.

PMID- 9264538
TI  - Occurrence of a para-nitrophenyl phosphate-phosphatase with calcineurin-like
      characteristics in Paramecium tetraurelia.
AB  - Using para-nitrophenyl phosphate (pNPP) as a substrate for enzymatic activity, we
      sought to identify CaN in Paramecium. We isolated three different pNPP
      phosphatases from the soluble fraction of Paramecium cells by anion-exchange and
      affinity column chromatographies. One, pNPP-phosphatase Peak I, is very similar
      to mammalian CaN. Divalent cation dependency, inhibition by calmodulin (CaM)
      antagonists (trifluoperazine, calmidazolium), and insensitivity to various
      phosphatase inhibitors (heparin, okadaic acid, sodium vanadate, etc.) show
      similarity to mammalian CaN rather than to any other Paramecium pNPP-hydrolyzing
      enzymes tested. Polyclonal antibodies against bovine brain CaN recognizing
      subunits A (61 or 58 kDa) and B (17 kDa) of brain CaN cross-reacted with a 63-kDa
      protein in fractions containing Peak IpNPP-phosphatase activity and coeluted
      calmodulin. Overlay assays using biotinylated brain calmodulin indicated Ca2+
      dependent CaM-binding by the 63-kDa protein. A Ca2+-binding protein with the same
      electrophoretic mobility as CaN B (17 kDa) was also present, though in other
      fractions from DEAE-cellulose chromatography. This finding strongly suggests
      that, in the absence of Ca2+, both subunits, A and B, were separated either
      before or during chromatographic processing. Our data support the existence of
      both subunits of a CaN-like phosphatase in Paramecium cells.

PMID- 9264539
TI  - Synthesis and kinetic studies of diphenyl 1-(N-peptidylamino)alkanephosphonate
      esters and their biotinylated derivatives as inhibitors of serine proteases and
      probes for lymphocyte granzymes.
AB  - Diphenyl 1-(N-peptidylamino)alkanephosphonate esters are highly reactive,
      specific, and aqueously stable irreversible inhibitors which can be used to probe
      the functions of many serine proteases, including the lymphocyte granzymes. We
      synthesized 16 peptide phosphonates with Ala, Met, Phe, or Val P1 amino acid
      residues, including two biotinylated derivatives for future functional and
      biochemical characterization of granzymes. The reactivity of the inhibitors was
      characterized with human leukocyte elastase (HLE), porcine pancreatic elastase
      (PPE), bovine chymotrypsin, and the granzymes of natural killer (NK) cells, which
      include a number of proteolytic activities (Asp-ase, Met-ase, etc.) that cleave
      peptide substrates with these residues in the P1 position. The reactivity and
      specificity of the phosphonates depended on the length and sequence of the
      peptidyl moiety and on the leaving group. Z-Ala-Ala-AlaP(OPh)2 was a good
      inhibitor of HLE and PPE (k(obsd)/[I] = 38 and 30 M(-1) s(-1), respectively) and
      had little reactivity with chymotrypsin. Z-Phe-Pro-Phe-P(OPh)2 was a good
      inhibitor of chymotrypsin (k(obsd)/[I] = 17,000 M(-1) s(-1)) and had little
      reactivity with the elastases. The leaving group of Z-MetP(OPh-4-Cl)2 made it a
      more effective chymotrypsin inhibitor than Z-MetP(OPh)2 (k(obsd)/[I] values of
      142 and 30 M(-1) s(-1), respectively). With granzymes, the compounds reacted with
      a fraction of the Met-ase, chymase, and Ser-ase activities and lacked reactivity
      with Asp-ase and tryptase. Z-MetP(OPh-4-Cl)2 was an excellent inhibitor of Met
      ase 1. Bi-Aca-Aca-Phe-Leu-PheP(OPh)2 appears to react specifically with one
      chymase while leaving other chymases untouched. Perforin-dependent lysis mediated
      by cytotoxic lymphocyte granules was inactivated by Z-Ala-Ala-AlaP(OPh)2, Z
      MetP(OPh-4-Cl)2, Z-Leu-PheP(OPh)2, and Bi-Aca-Aca-Phe-Leu-PheP(OPh)2. The
      biochemical properties and biological efficacy of these inhibitors make them
      suitable for cellular and physiological studies of granzyme function.

PMID- 9264541
TI  - Myelin is a preferential target of aluminum-mediated oxidative damage.
AB  - The capacity of Al3+ to promote oxidative damage to brain membranes was
      investigated both in vitro and in vivo. In vitro, Al3+ and related metals (Sc3+,
      Ga3+, In3+, Be2+, Y3+, and La3+) stimulated Fe2+-initiated lipid and protein
      oxidation in brain myelin and synaptic membranes. Al3+, Sc3+, Y3+, and La3+
      significantly promoted protein-associated carbonyl production in myelin, while in
      synaptic membranes, the stimulatory effect was observed in the presence of Ga3+,
      In3+, Y3+, Sc3+, and La3+. In myelin the magnitude of the stimulation of lipid
      oxidation followed the order Sc3+, Y3+, La3+ > Al3+, Ga3+, In3+ > Be2+. When
      compared to mitochondria and microsomal and synaptic membranes, myelin showed a
      marked susceptibility to Al3+-mediated lipid peroxidation. The differential
      susceptibility of myelin compared to synaptic membranes could not be explained by
      differences in membrane composition, since the relative content of negatively
      charged phospholipids (binding sites) was similar for both membranes, and myelin
      had a lower content of poly-unsaturated fatty acids (substrates of lipid
      oxidation) and a higher concentration of alpha-tocopherol compared to synaptic
      membranes. In a model of Al3+ intoxication imposed to mice during pregnancy and
      early development, a 72% higher content of lipid peroxidation products was found
      in brain myelin. The fluidity of myelin evaluated by the polarization
      fluorescence of 1,3-diphenylhexatriene was significantly higher in the Al3+
      intoxicated mice than in controls. Since myelin has a high relative content of
      lipid:protein compared to other membranes, these results support our hypothesis
      that ions without redox capacity can stimulate in vitro and in vivo lipid
      oxidation by promoting phase separation and membrane rigidification, thus
      accelerating lipid oxidation.

PMID- 9264540
TI  - A monoclonal antibody to avidin dissociates quaternary structure and curtails
      biotin binding to avidin and streptavidin.
AB  - An anti-avidin mAb, viz., H12G4, is shown to release bound biotin in a dose
      dependent manner from holoavidin and holostreptavidin and inhibit the binding of
      ligand to the two apoproteins. The release of biotin by this mAb is accompanied
      by quenching of ligand-induced enhanced fluorescence of the FITC-avidin
      conjugate. In terms of mechanism of release of bound biotin, we demonstrate that
      on binding to the Fab fragment of the mAb, the native tetrameric holoavidin
      undergoes dissociation progressively with time to monomers with no bound biotin
      associated with the latter. Based on the immunoreactivity associated with defined
      overlapping fragments of avidin obtained by chemical cleavage, the epitope
      recognized by mAb H12G4 has been localized to residues 58-96 of the primary
      sequence. By pepscan method of epitope mapping, this mAb is shown to identify a
      minimal core sequence of 87RNGK90 in avidin and a corresponding sequence of
      84RNAH87 in streptavidin.

PMID- 9264542
TI  - Characterization of a pollination-related cDNA from Phalaenopsis encoding a
      protein which is homologous to human peroxisomal acyl-CoA oxidase.
AB  - The first putative plant acyl-CoA oxidase cDNA has been isolated from a
      Phalaenopsis cDNA library constructed by poly(A)+ RNA extracted from petals 1 day
      after pollination. This cDNA, pOACO31, contains a 2100-bp open reading frame
      which encodes a polypeptide named PACO1 of 699 amino acids. The predicted
      isoelectric point of PACO1 is 8.74 and the molecular weight is 78,032 Da, similar
      to that of a monomer of predicted plant acyl-CoA oxidase. Southern blot analysis
      indicated that this gene occurs in one copy or a low number of copies per haploid
      genome. When compared with sequences in databases, PACO1 revealed significant
      similarity only to peroxisomal acyl-CoA oxidase particularly within 13 conserved
      regions and a putative FMN-binding site.

PMID- 9264543
TI  - Cloning, sequence, and expression of kynureninase from Pseudomonas fluorescens.
AB  - We have cloned the gene encoding kynureninase from Pseudomonas fluorescens using
      a restriction site polymerase chain reaction technique (RS-PCR) (G. Sarkar, R. T.
      Turner, and M. E. Bolander PCR Methods Appl. 2, 318-322, 1993) and expressed the
      enzyme in Escherichia coli DH5a F'. The kynureninase gene has an open reading
      frame (ORF) of 1251 base pairs that codes for a protein of 416 amino acids with a
      calculated molecular weight of 45,906. The protein purified from P. fluorescens
      has N-terminal threonine and an observed molecular weight of 45,787 by
      electrospray mass spectrometry, suggesting that the N-terminal methionine is
      removed by posttranslational processing. The complete gene was obtained by PCR
      and inserted into pTZ18U. The resultant plasmid was used to transform E. coli
      DH5alpha F', and these cells overexpressed kynureninase to about 37% of total
      soluble protein. The isolated recombinant protein has molecular weight and Km
      values identical to those of the native protein from P. fluorescens. The amino
      acid sequence exhibits 29% identity with those of rat and human kynureninases and
      32% identity with the amino acid sequence translated from a Saccharomyces
      cerevisiae ORF. Alignment of the four sequences shows a highly conserved region
      which corresponds to the pyridoxal-5'-phosphate (PLP) binding site of rat
      kynureninase. Based on this alignment, we predict that Lys227 and Asp212 in P.
      fluorescens kynureninase are involved in pyridoxal-5'-phosphate binding. P.
      fluorescens kynureninase also exhibits significant homology to the nifS gene
      product, cysteine desulfurase, and to eucaryotic serine/pyruvate
      aminotransferases, suggesting that it is a member of subgroup IV of the
      aminotransferase family of PLP-dependent enzymes.

PMID- 9264544
TI  - Probing energy coupling in the yeast plasma membrane H+-ATPase with acetyl
      phosphate.
AB  - The energy-rich compound acetyl phosphate (ACP) was examined as a substrate for
      energy-linked reactions by the yeast plasma membrane H+-ATPase. The hydrolysis of
      ACP was sensitive to inhibition by vanadate with an IC50 approximately 1 microM,
      which is comparable to the level obtained in the presence of ATP. A Km of 8.29 +/
      0.65 mM for the hydrolysis of ACP was approximately 10-fold higher than that
      obtained for ATP, while Vmax values of 8.66 +/- 0.29 and 7.23 +/- 0.34 micromol
      Pi mg(-1) min(-1) were obtained with ATP and ACP, respectively. ACP formed a
      phosphorylated intermediate that was efficiently chased with hydroxylamine. Both
      ACP and ATP effectively protected the enzyme from trypsin-induced inactivation
      and formed identical tryptic digestion patterns, suggesting that ACP mimics the
      formation of conformational intermediates induced by ATP. However, unlike ATP,
      ACP was unable to drive proton transport by H+-ATPase. In addition, a pma1-S368F
      mutant enzyme that is highly insensitive to inhibition by vanadate in the
      presence of ATP was largely sensitive to vanadate in the presence of ACP. These
      results are interpreted in terms of a reverse, short-circuit pathway of the
      normal P-type ATPase kinetic pathway, in which the formation of E2P by-passes the
      E1P high-energy intermediate. In this pathway, ACP favors the formation of an E2P
      conformational state, which can interact with classical inhibitors like vanadate,
      but possesses insufficient free energy to drive proton transport by the H+
      ATPase.

PMID- 9264545
TI  - Mitochondrial creatine kinase interaction with phospholipid vesicles.
AB  - The characteristics of the interaction of mitochondrial creatine kinase (mt-CK)
      with phospholipid vesicles are determined. The presence of negatively charged
      phospholipids is required to obtain a significant binding of mt-CK. The
      interaction seems to be largely of an electrostatic nature: it increases with
      increasing amounts of anionic phospholipid in liposomes and decreases when the
      ionic strength increases or when the pH of the medium is higher than the pI of mt
      CK. We have compared the effects of various effectors used to solubilize mt-CK
      from the mitochondrial membrane on the binding of mt-CK to liposomes: the
      nucleotide substrates ATP and ADP have no influence, parahydroxymercuribenzoate,
      a negatively charged organomercurial compound, partially decreases mt-CK binding;
      and the anticancer agent adriamycin efficiently prevents mt-CK binding. As
      monitored by the increase in absorbance, mt-CK causes vesicle aggregation. A
      differential scanning calorimetry study, using
      dimyristoylphosphatidylcholine/dimyristoylphosphatidylglycerol vesicles, shows
      that mt-CK produces a decrease in the enthalpy variation without any change in
      the position of the calorimetric peak maximum. This suggests a partial
      disorganization of the phospholipid bilayer upon interaction with mt-CK.

PMID- 9264547
TI  - Kinetic analysis of barley chitinase.
AB  - The endochitinase from barley is the archetypal enzyme for a large class of plant
      derived antifungal chitinases. The X-ray structure was solved previously in our
      laboratory and a mechanism of action proposed based on structural considerations.
      In this manuscript we report the use of a defined soluble substrate, 4
      methylumbelliferyl beta-N,N',N"-triacetylchitotrioside, to characterize kinetic
      parameters of the enzyme. The pH profile shows that activity is controlled by a
      base with a pKa of 3.9 (Glu 89) and an acid with a pKa of 6.9 (Glu 67). The Km
      using the synthetic substrate is 33 microM, and the k(cat) is 0.33 min(-1), while
      the Km for (GlcNAc)4 is 3 microM and k(cat) is 35 min(-1). Binding constants were
      measured for beta-linked oligomers of N-acetylglucosamine. The monomer does not
      bind and dissociation constants for the dimer, trimer, and tetramer are 43, 19,
      and 6 microM, respectively. Analysis of kinetic and dissociation constants proves
      the mechanism of barley chitinase is consistent with a Bi-Bi kinetic model for
      hydrolysis, with (GlcNAc)4 and water as substrates and (GlcNAc)2 as products.
      Substrate cleavage patterns show that (GlcNAc)6 is cleaved in half to (GlcNAc)3
      as well as into (GlcNAc)4 and (GlcNAc)2 with almost equal efficiency. NMR
      analysis of cleavage products confirms that the enzyme proceeds with anomeric
      inversion of products.

PMID- 9264546
TI  - Aluminum-induced structural alterations of the precursor of the non-A beta
      component of Alzheimer's disease amyloid.
AB  - The precursor of the non-A beta component of Alzheimer's disease amyloid (NACP)
      is a presynaptic protein whose function has been suspected to be tightly involved
      in neuronal biogenesis including synaptic regulations. NACP was suggested to seed
      the neuritic plaque formation in the presence of A beta during the development of
      Alzheimer's disease (AD). Recombinant NACP purified through heat treatment, DEAE
      Sephacel anion-exchange, Sephacryl S-200 size-exclusion, and S-Sepharose cation
      exchange chromatography steps appeared as a single band on SDS-PAGE with Mr of 19
      kDa. Its N-terminal amino acid sequence clearly confirmed that the protein was
      NACP. Interestingly, however, the protein was split into a doublet on a
      nondenaturing (ND)-PAGE with equal intensities. The doublet was located slightly
      above a 45-kDa marker protein on a 12.5% ND-PAGE. In addition, the size of NACP
      was more carefully estimated as 53 kDa with high-performance gel-permeation
      chromatography using a TSK G3000sw size-exclusion column. Recently, Lansbury and
      his colleagues (Biochemistry 35, 13709-13715) have reported that NACP exists as
      an elongated "natively unfolded" structure which would make the protein more
      actively involved in protein-protein interactions and Kim (Mol. Cells 7, 78-83)
      has also shown that the natively unfolded protein is extremely sensitive to
      proteases. Here, we report that the structure of NACP could be altered by certain
      environmental factors. Aluminum, a suspected risk factor for AD, converged the
      doublet of NACP into a singlet with slightly lower mobility on ND-PAGE.
      Spectroscopic analysis employing uv absorption, intrinsic fluorescence, and
      circular dichroism indicated that NACP experienced the structural alterations in
      the presence of aluminum such as the secondary structure transition to generate
      about 33% alpha-helix. This altered structure of NACP became resistant to
      proteases such as trypsin, alpha-chymotrypsin, and calpain. Therefore, it is
      suggested that aluminum, which influences two pathologically critical processes
      in AD such as the protein turnover and the protein aggregation via the structural
      modifications, could participate in the disease.

PMID- 9264548
TI  - Denatured proteins as cofactors for plasminogen activation.
AB  - Activation of covalently intact plasminogen by tissue-type plasminogen activator
      (tPA) is facilitated by a majority of proteins subjected to denaturing
      conditions. Except for heat-denatured apoferritin, the denatured proteins
      examined require partial proteolysis by plasmin for cofactor activity. The same
      proteins in their native state are resistant to proteolysis with plasmin and
      develop no activity. Denatured preparations of apoferritin, antithrombin, alpha1
      protease inhibitor, alpha2-macroglobulin, and albumin also accelerate des(1-77)
      plasminogen activation by tPA. The rate enhancements are comparable with that of
      the fibrin(ogen) fragments on a w/w basis. The cofactor activities are inhibited
      by 6-aminohexanoate and inactivated by pepsin. Analysis of heat-denatured
      apoferritin and albumin preparations by ultracentrifugation and gel
      chromatography indicates that cofactor is associated predominately with
      aggregates, which have binding capacity for both tPA and zymogen. Heat-denatured
      albumin pretreated with plasmin decreases K(M) and increases k(cat) for both
      intact plasminogen and des(1-77)-plasminogen activation by tPA, yielding
      catalytic efficiencies in excess of 8 x 10(3) M(-1) s(-1) and 2 x 10(4) M(-1) s(
      1), respectively. Because of enhanced plasmin-catalyzed proteolysis of
      plasminogen to des(1-77)-plasminogen, activation by urokinase-type plasminogen
      activator is also facilitated by denatured proteins; activation of des(1-77)
      plasminogen is not affected. It is concluded that denatured proteins serve as
      both cofactors and substrates in the fibrinolytic system, and that enhancement of
      plasminogen activation by denatured proteins is mechanistically indistinguishable
      from that observed with fibrin.

PMID- 9264549
TI  - Ingestion of Candida albicans down-regulates mannose receptor expression on rat
      macrophages.
AB  - The frequency of infection and death due to various Candida species has increased
      steadily during the past decade, with mucocutaneous candidal infections as a
      common problem in the immunocompromised host. Mononuclear phagocytes are
      important in phagocytosis of this organism. In areas where there are low levels
      of opsonins, the macrophage-specific mannose receptor plays a dominant role in
      mediating Candida albicans ingestion. Following receptor-mediated infection, the
      host macrophage produces inflammatory cytokines and mediators that lead to
      ultimate killing of the invading Candida. Infection of macrophages by pathogens
      often leads to altered function that might effect their subsequent host defense
      properties. For example, function of both the complement receptor type 3 and the
      mannose receptor are down-regulated following exposure to pathogens or pathogen
      derived products. In the current study, we have examined the down-regulation of
      mannose receptor expression following Candida infection and have investigated
      possible mechanisms that might be involved. Mannose receptor activity was
      decreased following 24 h postinfection with Candida. Both tumor necrosis factor
      and nitric oxide were produced during the infection, and inhibition of the these
      mediators partially blocked the effect on the receptor. Infection with Candida
      also inhibited the ability of dexamethasone to up-regulate mannose receptor
      expression. Finally, mannose receptor protein turnover was accelerated in Candida
      infected macrophages. We conclude that Candida down-regulates one of the
      receptors involved in its internalization through a combination of production of
      modulatory molecules and enhanced receptor degradation. These results support the
      hypothesis that pathogens that infect macrophages have the ability to alter the
      phagocytic pathways available for subsequent host defense.

PMID- 9264550
TI  - Characterization of rabbit UDP-glucuronosyltransferase UGT1A7: tertiary amine
      glucuronidation is catalyzed by UGT1A7 and UGT1A4.
AB  - A rabbit liver UDP-glucuronosyltransferase cDNA that is related to human and rat
      UGT1A7 has been identified. The predicted amino acid sequence of the UGT1A7l
      displays 80% similarity to that encoded by human HP4 (UGT1A9), but 81% to that
      predicted for human UGT1A7 and 77% to the rat UGT1A7 (UGTA2). The exons encoding
      human UGT1A7 and rat UGTA2 are the seventh of the series of cassette exons that
      flank the 3' common exon series of the UGT1A locus. Southern blot analysis
      demonstrates that the exon sequence encoding UGT1A7l is part of a larger cluster
      of highly related genes. The UGT1A7l RNA is expressed in both neonatal and adult
      liver, and unlike rat UGT1A2 which is inducible with Ah receptor ligands such as
      polycyclic aromatic hydrocarbons, rabbit UGT1A7l is not regulated when animals
      are exposed to these inducers. Following expression of UGT1A7l in COS-1 cells,
      glucuronidation activity was identified for small phenolic molecules like 4
      nitrophenol, bulky phenols as represented by 4-hydroxybiphenol and octylgallate,
      as well as 4-hydroxyestrone. In addition, UGT1A7l possesses catalytic activity
      toward tertiary amines like the tricyclic antidepressant imipramine. The pattern
      of UGT1A7l glucuronidation is similar to that observed for human UGT1A9, except
      tertiary amines are not subject to glucuronidation by human UGT1A9.
      Glucuronidation of tertiary amines is catalyzed principally by human UGT1A4 as
      well as rabbit UGT1A4. Although rabbit UGT1A7l catalyzes the formation of
      quarternary ammonium glucuronides, the Vmax is considerably less than that
      observed for rabbit UGT1A4. Overall, the characterization of rabbit UGT1A7l
      suggests that this protein represents the ortholog of the human UGT1A7, which to
      date has not been identified.

PMID- 9264551
TI  - Regulation of CYP3A9 gene expression by estrogen and catalytic studies using
      cytochrome P450 3A9 expressed in Escherichia coli.
AB  - Sexual dimorphism in the expression of CYP3A9, a novel form of CYP3A from rat
      brain, is shown for the first time in rat brain as well as in rat liver. CYP3A9
      expression is female specific in rat liver as judged by its 10-fold higher
      expression in females than in males. CYP3A9 gene expression was inducible by
      estrogen treatment both in male and in female rats. Ovariectomy of adult female
      rats elicited a drastic reduction on the mRNA level of CYP3A9 which could be
      fully restored by estrogen replacement. These results suggest that estrogen may
      play an important role in the female-specific expression of the CYP3A9 gene. P450
      3A9 recombinant protein was expressed in Escherichia coli by means of the pCWOri+
      expression vector and the MALLLAVF amino terminal sequence modification. This
      construct gave a high level of expression (130 nmol P450 3A9/liter culture) and
      the recombinant protein of the modified P450 3A9 was purified to electrophoretic
      homogeneity with a specific content of 10.1 nmol P450/mg protein from solubilized
      fractions through two chromatographic steps. The purified P450 3A9 protein was
      active in the metabolism of imipramine, erythromycin, benzphetamine, and
      ethylmorphine as well as 17beta-estradiol in a reconstituted system containing
      lipid and rat NADPH-P450 reductase. Of special interest is the finding that P450
      3A9 can catalyze the formation of desipramine with a turnover number of 4.9
      nmol/min/nmol P450, suggesting the possible involvement of this isoform in the
      metabolism of imipramine in brain. Optimal reconstitution conditions for P450 3A9
      activities required a lipid mixture (1:1:1 mixture of L-alpha-dilauroyl
      phosphatidylcholine, L-alpha-dioleoyl phosphatidylcholine, and
      phosphatidylserine) and GSH.

PMID- 9264552
TI  - Characterization of the aromatic hydrocarbon receptor gene and its expression in
      Atlantic tomcod.
AB  - Cytochrome P4501A1 (CYP1A1) mRNA is not inducible in Atlantic tomcod from the
      Hudson River that are treated with halogenated aromatic hydrocarbons (HAHs). In
      contrast, CYP1A1 mRNA is inducible in Hudson River tomcod that are treated with
      polycyclic aromatic hydrocarbons (PAHs) and in tomcod that are collected from
      cleaner rivers and treated with HAHs or PAHs. We hypothesize that CYP1A1
      transcription is inhibited in Hudson River tomcod because of down-regulation of
      the aromatic hydrocarbon receptor (AhR) pathway and that separate molecular
      pathways modulate CYP1A1 transcription in fish treated with HAHs and PAHs. We
      initially evaluated levels of hepatic nuclear protein binding at enhancer
      elements (DREs) in the regulatory region of tomcod CYP1A1. No difference in
      levels of protein binding was observed between tomcod from the Hudson and
      Miramichi (cleaner) rivers that were untreated or were treated with
      benzo[a]pyrene. In contrast, levels of protein binding were lower in tomcod from
      the Hudson River that were treated with TCB than in similarly treated fish from
      the Miramichi River, suggesting differences between the populations in the
      structure or expression of AhR pathway molecules. To address this possibility,
      AhR DNA sequences were characterized from tomcod cDNA and genomic DNA libraries.
      In tomcod and mammals, AhR is represented by 11 exons, overall peptide sizes are
      similar, and amino acid sequences at basic, helix-loop-helix, PAAS A, and PAAS B
      domains are highly conserved. In contrast, little similarity was observed between
      tomcod and mammals in the sizes or sequences of AhR exons 10 and 11, including
      the absence in tomcod of glutamine-rich domains. No differences in levels of
      hepatic AhR mRNA were observed between the two populations or treatment groups
      when tomcod were untreated or were treated with aromatic hydrocarbons. In
      contrast, variation in levels of AhR mRNA expression was observed among tomcod
      tissues; however, no relationship was observed between levels of AhR mRNAs and
      CYP1A1 mRNAs in tissues from chemically or vehicle control-treated fish. RFLP
      analysis revealed extensive variation in exons 10 and 11 of AhR cDNA among tomcod
      from different rivers. Our results suggest that variation between tomcod
      populations in CYP1A1 mRNA inducibility is reflected by differences in levels of
      inducible hepatic protein binding to DREs. However, levels of hepatic AhR mRNA
      are not down-regulated in the Hudson River population, are not affected by AH
      treatments, and levels of AhR mRNA expression are not responsible for the
      differential inducibility of CYP1A1 transcription.

PMID- 9264553
TI  - Comprehensive analysis of proteins which interact with the antioxidant responsive
      element: correlation of ARE-BP-1 with the chemoprotective induction response.
AB  - Transcriptional activation of the mouse glutathione S-transferase Ya gene by
      chemoprotective molecules is mediated through the interaction of trans-acting
      factors with an antioxidant responsive element (ARE) in the promoter region of
      this gene. In a step toward identifying those factors which bind productively to
      the GST Ya ARE, all of the discernible, specific ARE-binding proteins (ARE-BP) in
      nuclear extracts from HepG2 cells were systematically characterized. By gel
      mobility-shift analysis, seven specific ARE-BPs, termed ARE-BP-1 through 7 in
      order of increasing mobility, were observed that did not vary in concentration or
      migration between induced and uninduced cell extracts. The molecular weights of
      the individual ARE-BP subunits were determined by a two-dimensional
      electrophoresis protocol. Ferguson gel analysis of native protein size indicated
      that several of the ARE-BP-DNA complexes are composed of multiple protein
      subunits. Wild-type AREs and GST Ya ARE fragments and mutant sequences were
      evaluated for their ability to mediate induction in a reporter gene system in
      HepG2 cells. This same panel of sites was tested in an in vitro binding assay for
      the ability to compete for the ARE-BPs. A binding profile for each ARE-BP was
      compiled. Correlation between the ARE-BP binding profiles and induction results
      indicated that: (i) the ARE-BP-1 and ARE-BP-2 complexes formed only with AREs
      that supported induction, and (ii) the ARE-BP-4 complex formed with all inducible
      AREs, but it also bound to ARE mutants that failed to support induction. Based on
      the studies, an early composite regulatory element model for ARE-mediated
      expression is presented. ARE-BP-1 is proposed to be the mediator of the ARE's
      unique induction response to chemoprotective agents.

PMID- 9264554
TI  - Regulation of magnesium efflux from rat spleen lymphocytes.
AB  - Rat spleen lymphocytes (RSL) incubated at 37 degrees C in Mg-free medium (O-trans
      conditions) exibited Mg2+ efflux with apparent velocity of 0.2 nmol/mg
      protein/min. After 30 min, this process accounted for the mobilization of about
      15% of cell total Mg2+. Half of the Mg2+ efflux depended on extracellular Na+ and
      was stimulated by cAMP. IFN-alpha significantly enhanced Mg2+ efflux under O
      trans conditions as well as in the presence of physiological extracellular Mg2+.
      Pretreatment of RSL with indomethacin completely abolished IFN-alpha-induced Mg2+
      efflux, suggesting a crucial role for cyclooxygenase-dependent arachidonate
      metabolism. On the other hand, pretreatment of RSL with the PKA inhibitor (Rp)8
      Br-cAMPS prevented IFN-alpha stimulation of Mg2+ efflux, indicating the
      involvement of cAMP. Consistently, both IFN-alpha and exogenous PGE1 increased
      cAMP from 50 to 125 pmol/mg protein. Altogether these results show that IFN-alpha
      stimulates Mg2+ efflux by activating arachidonate metabolism and synthesis of
      prostaglandins. By influencing adenylcyclase activity, PGEs can eventually
      promote cAMP-dependent Mg2+ efflux, possibly through the activity of a Na-Mg
      antiport. In RSL, therefore, magnesium movements can be under the control of IFN
      alpha and, perhaps, of other cytokines, suggesting the involvement of Mg2+ in
      cell response to receptor-mediated stimuli.

PMID- 9264555
TI  - Inhibition of cartilage degradation and changes in physical properties induced by
      IL-1beta and retinoic acid using matrix metalloproteinase inhibitors.
AB  - Bovine cartilage explants were treated with 100 ng/ml recombinant human
      interleukin-1beta (IL-1beta) or 1 microM all-trans retinoic acid (RA) and changes
      in biochemical, biomechanical, and physicochemical properties were assessed.
      Additionally, samples cultured with IL-1beta or RA were treated with 4 microM
      recombinant human tissue inhibitor of metalloproteinases-1 (TIMP-1) or a
      synthetic metalloproteinase inhibitor (L-758,354) to inhibit this degradation.
      Treatment with IL-1beta or RA each resulted in >90% GAG loss after 8 days in
      culture. Addition of TIMP or L-758,354 to the culture media inhibited IL-1beta
      induced loss of tissue GAG by 40 and 65%, respectively, and inhibited RA-induced
      GAG loss by 35 and 65%, respectively. Analysis of degradation products in the
      culture media using a G1 antibody indicated that IL-1beta- and RA-treated plugs
      released 68-kDa fragments of aggrecan, corresponding to a segment of the aggrecan
      core protein from the G1 domain to the C-terminus NITEGE, consistent with
      "aggrecanase" activity. Release of the G1 fragment was inhibited by treatment
      with L-758,354. Both IL-1beta and RA induced significant loss of hyaluronan from
      cartilage explants after 8 days of exposure and HA loss was also inhibited by
      addition of L-756,354 to the culture media. IL-1beta, but not RA, induced a
      significant increase in swelling ratio (wet weight in 0.01 M NaCl normalized to
      wet weight in DMEM) after 8 days in culture, consistent with degradation of the
      collagen network, and the increase in tissue swelling was inhibited by treatment
      with TIMP-1 or L-758,354. Exposure to IL-1beta or RA resulted in significant
      changes in cartilage physical properties including streaming potential,
      equilibrium modulus, hydraulic permeability, and electrokinetic coupling
      coefficient after 8 days in culture, and these changes were inhibited by 40-90%
      by exposure to TIMP and by 50-90% by exposure to L-758,354. Measurement of
      dynamic streaming potential showed that changes due to treatment with IL-1beta
      alone were highly dependent in compression frequency, with dramatic changes seen
      at high frequency prior to changes in mechanical properties, and little initial
      change seen at low frequency. Streaming potential and equilibrium modulus of
      explants treated with RA decreased to 10% of their initial values after 8 days in
      culture, but decreased to only 40 and 90%, respectively, when treated with RA
      plus TIMP-1.

PMID- 9264556
TI  - Direct evidence for antioxidant effect of Bcl-2 in PC12 rat pheochromocytoma
      cells.
AB  - Mock-transfected PC12 rat pheochomocytoma cells and PC12 cells transfected with
      the bcl-2 gene, a gene associated with inhibition of apoptosis, were subjected to
      oxidative stress by incubation in the presence of the azo-initiator of lipid
      peroxyl radicals, 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN). Extraction and
      chromatographic analysis by two-dimensional TLC of the major phospholipid classes
      showed no differences in the phospholipid composition between the mock- and bcl-2
      transfected cell lines after incubation in the presence of 0.5 mM AMVN for 2 h at
      37 degrees C. A method consisting of incorporation of cis-parinaric acid into the
      constituent membrane phospholipids before exposure to AMVN was developed to
      improve the sensitivity of detecting lipid peroxidation in PC12 cells. Analysis
      of the pattern of changes in parinaric acid-labeled phospholipids after exposure
      to 0.25 and 0.5 mM AMVN by HPLC showed significant oxidation of
      phosphatidylcholine (PC), phosphatidylethanolamine (PEA), phosphatidylserine
      (PS), phosphatidylinositol (PI), and sphingomyelin (SPH) during a 2-h incubation.
      The extent of oxidation of each phospholipid class was dependent on the
      concentration of AMVN present up to 1 mM. Based on phospholipid fractional
      composition, the specific rates of PnA peroxidation in phospholipid classes were
      estimated. In mock-transfected PC12 cells, the order of AMVN-induced oxidation
      effectiveness was the same for both specific rates and relative rates: PC >> PEA
      > PS > SPH > PI. While a dramatic decrease in both relative and specific
      oxidation rates was observed for all phospholipid classes in bcl-2-transfected
      PC12 cells, the specific oxidation rates were higher for aminophospholipids (PEA
      and PS) than for other phospholipids. This suggests that antioxidant protection
      by bcl-2-related product(s) may be phospholipid-specific and that
      aminophospholipids are relatively less protected than the other phospholipids.
      The vitamin E analogue, 2,2,5,7,8-pentamethyl-6-hydrochromane, acted as an
      effective antioxidant in preventing oxidation of parinaric acid-labeled membrane
      phospholipids during incubation in the presence of AMVN and the extent of
      protection was approximately the same in both cell lines. Since, unlike the
      agents used to generate oxidative stress in other studies, temperature-driven
      generation of peroxyl radicals by AMVN is not dependent on intracellular
      metabolism, the results presented provide proof for antioxidant protection,
      rather than abrogation of radical generation afforded by bcl-2 transfection of
      PC12 cells.

PMID- 9264557
TI  - Superoxide-mediated cytotoxicity in superoxide dismutase-deficient fetal
      fibroblasts.
AB  - To investigate the roles of CuZn superoxide dismutase (CuZnSOD) and Mn superoxide
      dismutase (MnSOD) in oxygen radical-mediated cytotoxicity and to distinguish the
      actions of these two enzymes, fetal fibroblasts were derived from mouse fetuses
      that are either deficient in CuZnSOD (Sod1-/+ and -/-) or MnSOD (Sod2-1+ and -/-)
      for in vitro studies. Whereas the phenotype of the Sod1 mutant animals did not
      differ from that of their normal littermates, the growth of Sod1-/- fetal
      fibroblasts was only 25% of that of the -/+ and +/+ cells. On the other hand,
      although almost all homozygous Sod2 mutant animals (-/-) died within 10 days
      after birth, cultivation of Sod2-/- fetal fibroblasts was possible and their
      growth was about 60% that of -/+ and +/+ cells. When cultured cells were
      subjected to treatment with paraquat to assess their ability to grow in the
      presence of high levels of superoxide radicals, Sod1-/- cells were 80 times more
      sensitive and Sod2-/- cells were 12 times more sensitive to paraquat than wild
      type cells. In addition, whereas the loss of 50% CuZnSOD rendered Sod1-/+ cells
      almost twice more sensitive to paraquat than +/+ cells, loss of 50% MnSOD had no
      effect on paraquat sensitivity. Our results suggest that CuZnSOD-deficient cells
      are more sensitive to oxygen toxicity than are MnSOD-deficient cells, that
      paraquat causes free radical-induced damage in both the mitochondria and
      cytoplasm, and that SOD compartmentalized in the cytosol cannot compensate for
      the loss of SOD in the mitochondria and vice versa.

PMID- 9264558
TI  - Secondary cytoreductive surgery: who benefits from it?

PMID- 9264560
TI  - Surgical staging of endometrial cancer: evolution, evaluation, and responsible
      challenge--a personal perspective.

PMID- 9264559
TI  - Secondary cytoreductive surgery at second-look laparotomy in advanced ovarian
      cancer: a Gynecologic Oncology Group Study.
AB  - Reports which analyzed the effects of secondary cytoreductive surgery at second
      look laparotomy have often included small numbers of patients who have been
      treated with a variety of first-line chemotherapy regimens and those who may have
      progressed on first-line therapy. The purpose of this study was to analyze
      survival following secondary cytoreductive surgery at second-look laparotomy in
      patients with advanced ovarian cancer. Review of the surgical data of 153
      patients allowed classification of tumor size found at second-look laparotomy and
      tumor size remaining after cytoreduction. Multivariate analysis evaluated
      multiple risk factors for survival. Of 153 patients, 124 had macroscopic tumor at
      second-look laparotomy and 29 had microscopic disease only. Fifteen of 69 (22%)
      patients were found to have tumor > 1 cm in diameter and were cytoreduced to
      microscopic residual and 18/69 (26%) were left with 1 cm tumor. Twenty-one of 55
      (38%) patients with < or = 1 cm tumor were debulked to microscopic residual. The
      shortest survival relative to patients found to have microscopic disease at
      second-look laparotomy was observed among patients whose maximum tumor size
      remained > 1 cm following second-look laparotomy (relative risk = 3.1, P =
      0.0004). No difference in survival was seen between patients found to have
      microscopic disease and those cytoreduced to microscopic disease (P = 0.24). The
      risk of death was lower among patients debulked to a lower category (< or = 1 cm
      debulked to microscopic, relative risk = 0.48, P = 0.02; > 1 cm reduced to < or =
      1 cm, relative risk = 0.49, P = 0.02; > 1 cm reduced to microscopic, relative
      risk = 0.44, P = 0.01). Whether this apparent beneficial effect of cytoreductive
      surgery at second-look laparotomy reflects the biology of the tumor which allows
      surgical cytoreduction or the effects of cytoreduction can only be addressed in a
      randomized prospective trial.

PMID- 9264561
TI  - Establishing SGO's strategic direction for the next millennium. Society of
      Gynecologic Oncologists.

PMID- 9264562
TI  - Effect of low-dose oral etoposide on serum CA-125 in patients with advanced
      epithelial ovarian cancer.
AB  - The effect of oral etoposide on CA-125 serum levels was evaluated in 17 patients
      with epithelial ovarian cancer and progressive disease during, or relapsing
      after, prior chemotherapy. Only three patients had measurable lesions at
      extraperitoneal sites. Five had no measurable lesions. The oral etoposide dose
      was 50 mg b.d. for 7 days every 3 weeks, escalating to 10 or 14 days and
      continued until clinical progression. CA-125 after 4 courses was compared to
      baseline (CA-125 ratio). The rate of change of CA-125 (s, slope of the
      exponential regression curve) during the first 4 courses was compared to s over a
      similar period before treatment. One patient had a clinical partial response. Two
      other patients had a biochemical response (CA-125 ratio <0.5). Although the
      biochemical response rate was modest (12.5%), a decrease of s was observed in
      14/16 patients (P = 0.02). The mean change of s represented an increase of mean
      doubling time from 52 to 693 days. No patients were withdrawn because of
      toxicity. General malaise, nausea, diarrhea, and anemia were the most important
      side effects. At the given dose schedule, oral etoposide shows activity in
      advanced ovarian cancer if the rate of change of CA-125 is used as a measure of
      activity.

PMID- 9264564
TI  - Efficient lysis of CD44v7/8-presenting target cells by genetically engineered
      cytotoxic T-lymphocytes--a model for immunogene therapy of cervical cancer.
AB  - Variant proteins of the CD44 surface glycoprotein family are expressed on many
      different human tumors and their lymph node metastases. An epitope encoded by
      sequences of variant exons CD44v7 and v8 and recognized by the monoclonal
      antibody VFF17 is frequently detected in cervical cancer, whereas the normal
      cervical epithelium lacks expression of this epitope. We have developed an
      immunotherapeutic approach for cervical cancer based on the expression of this
      CD44v7/8 epitope. The single chain antigen-binding fragment of VFF17 was fused to
      a signal transducing protein (zeta-chain) of the T-cell receptor complex (TCR)
      and was introduced into a retroviral gene transfer vector. Gene transfer was
      applied to the murine cytotoxic T-cell line cl96. All recombinant clones
      expressed the fusion protein on their cell surface. Functionality of the
      recombinant fusion protein was tested by subjection of several recombinant clones
      to in vitro cytotoxicity assays. CD44v7/8-expressing target cells were killed
      efficiently by reprogrammed cl96 in an MHC-independent fashion, whereas CD44v7/ 8
      negative cells were not affected. These transfected T cell lines will now be
      tested in vivo using immune-deficient mice bearing CD44v7/8-expressing tumors.

PMID- 9264563
TI  - Regulation of human papillomavirus type 18 in vivo: effects of estrogen and
      progesterone in transgenic mice.
AB  - We examined the in vivo effect of estrogen, progesterone, RU 486, and pregnancy
      on the upstream regulatory region (URR) of human papillomavirus (HPV) 18
      transgenic mice. The mice contain the bacterial reporter beta-galactosidase gene
      under control of the HPV 18 URR. Pregnant transgenic mice were sacrificed on
      various days of gestation and the level of URR activation was determined. Another
      group of female transgenic mice was ovariectomized at 4 to 6 weeks of age.
      Pellets of estradiol, progesterone, progesterone + RU 486, or placebo were
      implanted 1 to 2 weeks after ovariectomy. Mice were sacrificed after pellet
      implantation to examine acute and chronic effects. Marked increases in URR
      activation during pregnancy were observed. Progesterone was found to activate the
      URR acutely. Significantly higher activation was demonstrated at 24 hr in the
      progesterone group compared to placebo (P < 0.01). Activation with progesterone
      at 24 hr was significantly higher than at any other time point (P < 0.001). A
      trend toward decreasing activation over time was demonstrated in the progesterone
      group (r = -0.87, P = 0.0001). RU 486 does not block the activation of
      progesterone in our model. Estradiol activates the URR acutely compared to
      placebo (P = 0.034). This in vivo model demonstrates activation of the URR in
      response to exogenous estrogen, progesterone, and pregnancy. These data may have
      clinical implications for women who harbor high-risk HPV.

PMID- 9264565
TI  - Involvement of annexin V in antiproliferative effects of gonadotropin-releasing
      hormone agonists on human endometrial cancer cell line.
AB  - We studied the involvement of annexin V in the antiproliferative effects of
      gonadotropin-releasing hormone (GnRH) agonists on human endometrial cancer cell
      line HHUA. HHUA cell line expressed mRNA for GnRH receptors as assessed by
      reverse transcriptase-PCR with oligonucleotide primers. In the presence of
      buserelin, the proliferation of this cell line was significantly (P < 0.01)
      reduced to 60% of control after 72 hr. Peak intracellular concentrations of
      annexin V, equivalent to about twice the control value, were obtained after 48 hr
      exposure to buserelin. Intracellular annexin V concentration was increased not
      only by buserelin, but also by protein kinase C (PKC) activator. However, there
      was no increase in intracellular annexin V concentration when cells were
      incubated with PKC inhibitor before the addition of buserelin. The results
      suggest that GnRH agonists inhibit cell proliferation by increasing intracellular
      concentrations of annexin V, an effect mediated by the activation of PKC.

PMID- 9264566
TI  - Telomerase activation in in vitro and in vivo cervical carcinogenesis.
AB  - Telomerase activity is found in the majority of human cancers, but not in most
      normal tissues. It is generally accepted that there is a multistep process in
      human carcinogenesis. Studying the role of telomerase activation in this process
      may provide new information to further our understanding of the pathological
      process of clinical lesions. In the present study, telomerase activity was found
      in HPV-immortalized and cigarette smoke condensate (CSC)-transformed malignant
      cell lines established in a cervical carcinogenesis model and in cell lines
      derived from cervical intraepithelial neoplasias (CINs) and carcinomas. With
      exfoliated cell samples, telomerase activity was detected in 3 of 41 (7%) normal
      cervices, 10 of 25 (40%) CINs, and all 20 (100%) carcinomas. Telomerase
      activation was significantly higher in CINs than in normal cervices (chi2 = 7.42,
      P < 0.01) and was much higher in invasive carcinomas than in CINs (chi2 = 18.00,
      P < 0.005). Our observations suggest that telomerase activation is a relatively
      early-stage event in cervical carcinogenesis, and this activation is associated
      with the initiation and progression of cervical lesions. Detection of telomerase
      activity may serve as a tool for diagnosis and prognosis of cervical neoplasias.

PMID- 9264567
TI  - Immunohistochemical detection of CD44 splice variant expression in premalignant
      lesions of the cervix and benign cervical epithelium.
AB  - The expression of specific CD44 splice variants in malignant tumors has been
      shown to be associated with metastasis and poor prognosis. In previous studies we
      have detected aberrant expression of the transmembranous cell adhesion molecule
      CD44 in cervical cancer. Therefore, we now focus on its role in intraepithelial
      dysplastic lesions of the cervix. Forty-five cervical intraepithelial neoplasias
      (CIN), grades I to III, were investigated immunohistochemically for three
      different splice variants of CD44 (v5, v6, and v7-8). A negative correlation of
      CD44v5 (Kendall correlation coefficient r = -0.25, P < 0.05) expression with the
      grade of CIN was found. In normal squamous epithelium of the cervix, the staining
      reaction of CD44v5 was confined to the basal and the parabasal cell layers. In
      dysplastic lesions a diffuse and weaker staining pattern of the entire epithelium
      was observed. Our data suggest a loss of CD44v5 epitope during dysplastic
      transformation. It seems that expression of CD44 splice variants is not a
      continuous process in the natural history of cervical cancer, and the pattern of
      CD44 splice variant expression is changed during carcinogenesis.

PMID- 9264568
TI  - Comparison of endometrial changes among symptomatic tamoxifen-treated and
      nontreated premenopausal and postmenopausal breast cancer patients.
AB  - Breast cancer patients who received tamoxifen as adjuvant therapy have been
      reported to have more endometrial lesions such as polyps, hyperplasia, or
      carcinoma. We conducted a prospective study to elucidate the endometrial changes
      of premenopausal and postmenopausal breast cancer patients with tamoxifen. Sixty
      seven symptomatic breast cancer patients who had been on tamoxifen treatment,
      including 34 premenopausal and 33 postmenopausal patients, and another group of
      48 patients who had not been on tamoxifen, including 25 premenopausal and 23
      postmenopausal patients, were recruited. Symptomatic patients were defined as
      having hypermenorrhea or abnormal vaginal bleeding among premenopausal patients
      or postmenopausal bleeding among postmenopausal patients. Endometrial thickness
      and uterine size determined by vaginal ultrasonography, histologic findings, and
      risk factors for endometrial cancer were compared. The mean endometrial thickness
      and uterine size showed no statistically significant difference in premenopausal
      patients with (n = 34) or without (n = 25) tamoxifen treatment, whereas there was
      a significant difference in the postmenopausal patients with (n = 33) or without
      (n = 23) tamoxifen treatment (12.11 +/- 12.38 mm vs 5.41 +/- 2.70 mm, P = 0.025;
      234.71 +/- 76.36 cm3 vs 108.81 +/- 81.27 cm3, P = 0.0018, respectively). The
      frequency of endometrial histopathologic findings was 23.5% (8/34) in tamoxifen
      treated women compared with 12.0% (3/25) in nontreated women (P = 0.269) in the
      premenopausal groups. In contrast, it was remarkably high with 66.7% (22/33) in
      tamoxifen-treated women compared with 30.4% (7/23) in the nontreated women in the
      postmenopausal groups (P = 0.025). There were four postmenopausal patients with
      tamoxifen, including three with atypical endometrial hyperplasia and one
      endometrial carcinoma, in contrast to no postmenopausal nontreated patients,
      although this difference did not reach statistical significance in this study (P
      = 0.096). There was a remarkably high prevalence of endometrial histopathologic
      findings in symptomatic tamoxifen-treated breast cancer patients, especially
      postmenopausal women. Tamoxifen might be associated with premalignant or
      malignant changes in postmenopausal endometrium. Thus timely, aggressive
      histologic assessment such as curettage or hysteroscope should be performed to
      detect the endometrial lesions when symptoms occur. Vaginal ultrasonography could
      be a useful tool to detect the endometrial lesions.

PMID- 9264569
TI  - Expression of nm23/nucleoside diphosphate kinase-A protein in endometrial
      carcinoma.
AB  - A metastatic tumor suppressor role for the nm23 gene product in breast carcinoma
      has been proposed. The biologic significance of nm23/NDP kinase-A (NDPK-A)
      expression in endometrial carcinoma remains undetermined. We sought to (1)
      characterize the pattern and intensity of nm23 protein expression in endometrial
      carcinoma and (2) assess the relationship between intensity/pattern of nm23
      protein immunostaining and treatment response assessed by progression-free
      survival and survival to death. Formalin-fixed paraffin-embedded sections from
      234 patients with endometrial cancer were immunostained with a mouse monoclonal
      IgG to nm23/NDPK-A protein. In most specimens of endometrial carcinoma (67.5%),
      nm23 expression was strongly upregulated. No association was found between either
      intensity (0 vs 1, 2, 3) or pattern (nuclear membrane vs cytoplasmic) of
      immunostaining and FIGO stage, ploidy status, histologic subtype, myometrial
      invasion, progression-free survival, or survival to death. Absence of nm23
      staining (0 vs 1, 2, 3) was significantly associated with lower tumor grades (P =
      0.02). For stage I patients, moderate to strong nm23 immunostaining intensity (2,
      3) was associated with a trend toward diminished progression-free survival (P =
      0.08). Our data imply a heterogeneity of nm23 protein expression and possible
      distinct biologic roles for nm23 in endometrial compared with breast or ovarian
      carcinoma.

PMID- 9264570
TI  - Phase II trial of doxorubicin, 5-fluorouracil, etoposide, and cisplatin in
      advanced or recurrent endometrial carcinoma.
AB  - We have previously reported an overall response rate of 41% and a median survival
      duration of 14 months in a series of 49 patients with metastatic or recurrent
      endometrial carcinoma treated by a combination of etoposide, 5-fluorouracil, and
      cisplatin. In order to increase response rate and survival duration, doxorubicin
      was added to this combination. From August 1992 to January 1996, 20 consecutive
      patients were treated with a monthly combination chemotherapy consisting of
      doxorubicin 30 mg/m2 i.v. Day 1, 5-fluorouracil 600 mg/m2 i.v. Days 1 to 3,
      etoposide 80 mg/m2 i.v. Days 1 to 3, and cisplatin 35 mg/m2 i.v. Days 1 to 3
      (AFEP). All patients were evaluable for response and toxicity. Median age was 62
      years (range 45-72). Two to eight cycles were delivered (median 5). Two of 20
      patients had complete response and 7 of 20 had partial response. The objective
      response rate was 45% (CI 95%: 23-68%). The median survival duration was 17
      months. The median progression-free survival was 8 months. Major toxic effect was
      myelosuppression: 75% of grade 3 and 4 leukopenia and 20% of grade 3 and 4
      thrombocytopenia. Seven patients (35%) developed infection and 4 (20%) were
      hospitalized once or more for toxicity. These results indicate that AFEP is an
      effective combination therapy in metastatic endometrial carcinoma but its
      toxicity is unacceptable.

PMID- 9264571
TI  - Expression of epidermal growth factor and androgen receptors in ovarian cancer.
AB  - Ovarian cancer is the second most common malignancy of the female reproductive
      tract. Approximately 50% of ovarian cancers have elevated levels of epidermal
      growth factor receptor (EGFR). This overexpression is correlated with a poor
      prognosis for patient survival. Ovarian cancers also express a number of sex
      steroid receptors. The androgen receptor (AR) is the predominant sex steroid
      receptor and is expressed in over 80% of ovarian cancers. We investigated whether
      a relationship exists between EGFR and AR in ovarian cancer. Sixty serous
      cystadenocarcinomas were analyzed for their relative levels of EGFR and AR by
      Western blot analysis. Data were analyzed by Student's t test and linear
      regression analysis for statistical significance. More than 98% of the tumors
      expressed detectable levels of EGFR, while 65% of the tumors expressed detectable
      levels of AR. The levels of EGFR (mean +/- SEM) were found to be significantly (P
      < 0.01) higher in AR+ (516 +/- 15) than in AR- (304 +/- 57) tumors. EGFR levels
      significantly correlated to AR levels (r = 0.49, P < 0.001). These results
      demonstrate an association between EGFR and AR levels in ovarian cancer. Whether
      this association represents a causal or a casual relationship remains to be
      determined.

PMID- 9264572
TI  - Risk for breast and colorectal cancers subsequent to cancer of the endometrium in
      a population-based case series.
AB  - The purpose of this study was to estimate the relative risk of breast and
      colorectal cancers in women who were previously diagnosed with endometrial
      cancer. This study was conducted using a population-based cohort of 2347 women
      diagnosed with invasive cancer of the endometrium between January 1, 1984, and
      December 31, 1995 in Orange County, California. Only women with a diagnosis of
      invasive endometrial cancer at age 80 years old or below were included in the
      analysis (N = 2170). In this same cohort, metachronous and synchronous breast and
      colorectal cancers were ascertained and the risk of developing one or the other
      type of neoplasm was compared to the expected number of cases derived from cancer
      incidence in California by age, 1988-1992. We found a statistically increased
      risk of breast cancer as a second primary, while the observed incidence in
      colorectal risk did not reach statistical significance. The association between
      endometrial cancer and breast and possibly colorectal cancer indicates the
      importance of common etiologies for these cancers.

PMID- 9264573
TI  - Primary radiation, cisplatin, and 5-fluorouracil for advanced squamous carcinoma
      of the vulva.
AB  - OBJECTIVE: To evaluate a regimen of radiation and chemotherapy as an alternative
      for those patients in whom the location and extent of advanced vulvar carcinoma
      make pelvic exenteration the only surgical option. METHODS: Between December 1988
      and March 1995, 14 patients with primary squamous carcinoma of the vulva who were
      not candidates for standard radical vulvectomy were treated with radiation
      therapy in combination with cisplatin and 5-fluorouracil (5-FU) chemotherapy at
      the Albany Medical Center. Patients ranged in age from 40 to 90 years, mean 68.
      Tumors were stage III in 9 patients and stage IV in 5 patients. Treatment
      included two cycles of chemotherapy with cisplatin (50 mg/m2) and 5-FU (1000
      mg/m2/24 x 96 hr) in addition to radiation therapy. Total radiation doses to the
      vulva and groins ranged from 50 to 65 Gray (Gy), with pelvic doses of 45 to 50
      Gy. Surgical excision of the primary site was not performed in patients who had
      complete clinical response. RESULTS: Acute complications included desquamation
      requiring treatment interruptions in 5 patients and deep venous thrombosis in 1
      patient. Delayed complications were limited to small bowel obstruction and
      colonic stricture in one patient. There was a 92% response rate with complete
      responses in 9 patients (64%). Among patients with complete clinical response,
      there has been only one recurrence with follow-up of 7-81 months, mean 36.5. All
      patients with partial responses died, with survival of 8-25 months, mean 15.7.
      CONCLUSIONS: This combination of chemoradiation was found to be effective therapy
      for locally advanced vulvar carcinoma, with acceptable morbidity even in an
      elderly population. Surgical excision of the primary site is not necessary in
      patients with complete response.

PMID- 9264574
TI  - Hydroxyurea, 5-fluorouracil infusion, and cisplatin adjunct to radiation therapy
      in cervical carcinoma: a phase I-II trial of the Gynecologic Oncology Group.
AB  - BACKGROUND: In a previous study, the Gynecologic Oncology Group (GOG) compared
      hydroxyurea (HDXR) and the combination of cisplatin (C) and 5-fluorouracil (5-FU)
      infusion as potentiators of radiation therapy. This study was undertaken to
      determine whether these two regimens could be combined, concurrent with pelvic
      radiation therapy in patients with locally advanced cervical cancer. METHODS: The
      GOG entered 75 eligible and evaluable patients on a Phase I-II evaluation of
      HDXR, C, and 5-FU as adjuncts to radiation therapy for locally advanced carcinoma
      of the cervix. All patients had histologically verified primary disease and
      confirmed negative para-aortic lymph nodes. Eligibility was limited to clinical
      stage IIB through IVA. HDXR was given orally, twice weekly at a dose of 2.5 g/m2;
      C on Days 1 and 29 at 50 mg/m2; and 5-FU by 96-hr infusion on Days 2-5 and 30-33
      at a starting dose of 800 mg/m2. RESULTS: Forty-eight (64%) patients had stage
      IIB disease, 25 (33%) had stage IIIB, and 2 had stage IVA tumors. Primary tumors
      4 cm or less in size were present in 15 patients, between 4 and 6 cm were in 27
      patients, and larger than 6-cm were observed in 33 patients. Grade 3/4 acute
      toxicity was experienced by 41 (54.7%) patients. These acute toxicities caused
      delays in prescribed radiation therapy of more than 1 week in 14 (18.9%) and low
      doses of drug in 16 (21.3%), and only 26 (34.7%) patients had the scheduled dose
      escalation of 5-FU on their second course. Clinical response was excellent with
      complete and partial response rate of 93.3%. Median time to progression has not
      been reached. CONCLUSION: Although this dose and schedule could be successfully
      administered, the delays in therapy should be avoided by a lower starting dose of
      hydroxyurea. Stomatitis was not a dose-limiting toxicity. These results have
      formed the basis of a phase III trial comparing this regimen to two other
      chemoradiation regimens.

PMID- 9264575
TI  - Tumor-associated proteolytic factors uPA and PAI-1 in endometrial carcinoma.
AB  - The levels of plasminogen activator urokinase (uPA) and of its inhibitor (PAI-1)
      were measured by use of ELISA in the cytosol of tissue homogenates obtained from
      endometrial carcinomas and the marginal, tumor-free endometrium of postmenopausal
      patients (n = 64). Significantly higher median levels of uPA and PAI-1 were found
      in malignant endometrium (uPA 1.89 ng/mg, PAI-1 3.04 ng/mg) compared to tumor
      free endometrium (uPA 0.84 ng/mg, PAI-1 1.01 ng/mg). Concerning uPA, no
      significant differences were found in dependence on histomorphological prognostic
      factors (staging, grading), but the median level of PAI-1 was significantly
      higher in G2/G3 carcinomas compared to G1 tumors (5.08 ng/mg vs 2.19 ng/mg).
      Because of the good prognosis of operated patients with endometrial carcinomas,
      the prognostic value of uPA and PAI-1 can only be decided by a larger number of
      patients and a long observation time.

PMID- 9264576
TI  - Major sequence variants in E7 gene of human papillomavirus type 16 from cervical
      cancerous and noncancerous lesions of Korean women.
AB  - Geographic specificity of nucleotide sequence variations in the coding and
      noncoding regions of HPV 16 genome has been reported. Little has been known,
      however, regarding whether these naturally occurring sequence variations of HPV
      16 may result in marked differences in biological properties, such as oncogenic
      potential. This study was performed to identify sequence variants in the HPV 16
      E7 gene derived from Korean women with cervical cancerous and noncancerous
      lesions, and to assess the association between the sequence variant and the
      cervical cancer. We examined E7 variants of HPV 16 in a total of 157 patients
      with no cervical disease (NCD, n = 87) or cervical neoplasia (cervical
      intraepithelial neoplasia 3, n = 21; cervical carcinoma, n = 49), using the
      nested polymerase chain reaction (PCR) and the PCR-directed sequencing methods
      with outer consensus and inner type-specific primers. Forty-two (NCD, n = 9; CIN
      3, n = 6; cervical carcinoma, n = 27) of 157 cervical samples contained HPV 16 E7
      DNA, but only 8 had prototype sequences. Four variants of the HPV 16 E7 gene were
      identified. The variant with a single nucleotide change at position 647 (A --> G,
      Asn --> Ser) was found in about 60% of DNA samples with HPV 16. The second most
      common variant, found in 16.7% of cases, had three silent mutations at positions
      732 (T --> C), 789 (T --> C), and 795 (T --> G). Two other variants were
      detected, one in a patient with cervical cancer and the other in a patient with
      no cervical disease. One had a single nucleotide change at position 666 (G --> A)
      and the other had one silent mutation at position 796 (T --> C). The most common
      variant in Korea has a change of nucleotide affecting the predicted amino acid
      related with high antigenicity and binding to retinoblastoma protein. There was a
      statistically significant trend for this variant to be more frequently detected
      in cancerous lesions of the uterine cervix than in noncancerous lesions. These
      data suggest that naturally occurring sequence variants of HPV 16 E7 gene may
      have different oncogenic properties.

PMID- 9264577
TI  - Sequence variation in the upstream regulatory region of HPV 18 isolates from
      cervical cancers.
AB  - This study describes sequence variation in both the enhancer and promoter
      segments of the upstream regulatory region (URR) of 28 human papillomavirus (HPV)
      type 18 isolates from cervical cancers, 25 from women treated at an Australian
      center and three from overseas included for comparison. No large-scale changes
      were found in either region. Fourteen substitutions were identified in the
      enhancer region with the number in individual isolates ranging from one to eight.
      Four substitutions impacted cellular transcription factor binding sites but there
      were no obvious associations with clinicopathological variables. The promoter
      segment was found to be more highly conserved than the enhancer, but four of the
      five point mutations identified involved cellular transcription factor binding
      motifs including a substitution of C for T at nt 104 which affected 21 samples.
      This change was found to impact upon a previously unrecognized Yin Yang (YY1)
      binding site. Electrophoretic mobility shift assays (EMSA) showed that this
      substitution significantly reduced protein-DNA binding and evidence was sought
      for its possible clinical implications. Of the 24 women with less than Stage III
      disease and known clinical outcome, tumor recurrence was observed in all of the 6
      women whose isolates had the "prototype" T at nt 104, whereas only 8 of the 18
      cancers with the mutation at this YY1 site recurred. This is the first report on
      URR variation in HPV 18 isolates from the South Pacific region. The study also
      provides initial data on diversity in the promoter region and preliminary
      evidence suggesting that a specific point mutation in this region may be
      clinically significant.

PMID- 9264578
TI  - Phase I/II study of intraperitoneal floxuridine and platinums (cisplatin and/or
      carboplatin).
AB  - Previous studies have shown that intraperitoneal (i.p.) floxuridine (FUDR) is
      tolerated at a dose of 3 g x 3 days given in 1.5-2 L of normal saline (NS). In a
      randomized phase II trial by the Southwest Oncology Group, this treatment was
      selected for further study because of a favorable 1-year progression-free
      survival. We have now evaluated ip FUDR in full doses combined with i.p.
      cisplatin given on the third day at a dose of 60 mg/m2 in 500 mL of NS.
      Intraperitoneal carboplatin was partially or fully substituted for i.p. cisplatin
      in patients with symptomatic neuropathies. All patients also received i.p.
      leucovorin, as previously piloted for fluoropyrimidine modulation. Seven patients
      with symptomatic ascites or measurable tumors were entered, as were 11
      asymptomatic patients with minimal residual (< or = 1 cm) epithelial ovarian
      cancer. Six cycles of the combination of i.p. FUDR + cisplatin were completed in
      three patients; however, the combination of FUDR with both platinums was
      particularly well tolerated. Intraperitoneal FUDR + carboplatin (AUC of 5) was
      associated with some grade 3 and 4 thrombocytopenia and neutropenia. Eight of
      these 11 patients are alive, and 3 have been continuously with no evidence of
      disease exceeding 32 months. The regimen of i.p. FUDR + i.p. cisplatin (or i.p.
      FUDR with both platinums) is suitable for a phase III trial testing i.p. therapy
      either from the outset (e.g., i.p. up front) or after achieving clinical complete
      responses from initial treatment without intervening relapse (i.e., i.p.
      consolidation) in comparison to i.p. cisplatin.

PMID- 9264579
TI  - Detection of serologic neutralizing antibodies against HPV-11 in patients with
      condyloma acuminata and cervical dysplasia using an in vitro assay.
AB  - This study was designed to investigate if neutralizing antibodies against HPV-11
      are detectable in the serum of patients with condyloma acuminata (CA) or cervical
      intraepithelial neoplasia (CIN) using an in vitro infectivity assay for HPV-11.
      Purified HPV-11 virions were extracted from xenografted condyloma tissues
      implanted into athymic mice and used to infect cultured neonatal human foreskin
      keratinocytes (HFK) and an immortalized adult skin cell line (HaCaT). The
      presence of HPV-11-specific E1--E4 mRNA as detected by reverse transcriptase
      polymerase chain reaction was indicative of early infection. Sera previously
      characterized for reactivity to HPV-11 and HPV-11 VLP (virus-like particles) by
      ELISA were tested for the ability to prevent HPV-11 in vitro infectivity.
      Neutralizing antibodies against HPV-11 were demonstrated when monoclonal
      antibodies or patient serum preincubated with HPV-11 virions prevented the
      infection of either of the two cell cultures, as shown by the absence of the E1-
      E4 mRNA transcript. Eleven (of 20) patients with CA were strongly ELISA reactive
      against HPV-11 virus-like particles. Five of these 11 patients also had
      detectable levels of neutralizing antibodies in their serum. It was also
      demonstrated that the neutralizing properties of the serum were titratable by
      endpoint dilution. None of 15 patients with CIN had detectable neutralizing
      antibodies against HPV-11. Neutralizing antibodies against HPV-11 can be detected
      in some patients with CA and the neutralizing effects of the patient sera can be
      titrated by endpoint dilution. The in vitro assay for the detection of
      neutralizing antibodies against HPV-11 may have utility for investigating the
      natural history of HPV infection and resolution, as well as assessing the
      efficacy of any putative HPV vaccine.

PMID- 9264580
TI  - Isolated vaginal recurrences in endometrial carcinoma: treatment results using
      high-dose-rate intracavitary brachytherapy and external beam radiotherapy.
AB  - PURPOSE: To evaluate the long-term disease control, survival and complication
      rates using high-dose-rate intracavitary brachytherapy (HDRB) and external beam
      radiotherapy (EBRT) for patients found to have isolated vaginal recurrences from
      early-stage endometrial adenocarcinoma following total abdominal hysterectomy and
      bisalpingo-oophorectomy (TAH BSO). MATERIALS AND METHODS: Twenty patients
      originally diagnosed with early-stage endometrial adenocarcinoma (FIGO stage I or
      II) following TAH BSO developed isolated vaginal recurrences and were referred to
      our radiation oncology department for definitive treatment. The median time
      between TAH BSO and vaginal recurrence was 24 months. Thirteen patients received
      combined modality treatment (EBRT + HDRB) and seven patients received HDRB only.
      Median prescribed dose was 4400 cGy by EBRT and 2400 cGy to the vagina mucosa
      surface by HDRB in the combined modality group. Median prescribed dose was 3500
      cGy to the vagina mucosa surface for the HDRB only group. These patients were
      followed for a median duration of 47.5 months following treatment for isolated
      vaginal recurrence. RESULTS: Eighteen of 20 patients (90%) achieved a complete
      response to therapy and the remaining 2 achieved a partial response. Four of 18
      complete responders developed a second recurrence within 30 months following
      radiotherapy. Ten-year cumulative local control rate was 74%. Ten-year cumulative
      cause specific and disease-free survival rate was 71 and 46%. Overall late
      complication rate was 15%; there were no grade 3 or 4 late complications. Three
      patients developed grade 2 late complications from treatment; all 3 were from the
      combined modality group (HDRB + EBRT). CONCLUSION: The use of HDRB resulted in
      high complete response rates and durable long-term disease-specific survival in a
      substantial percentage of patients. To our knowledge, this study represents the
      first published results on treatment of vaginal recurrences with HDRB. Although
      the number of patients in this study is small, treatment results compare
      favorably to those obtained from patients treated with low-dose-rate
      brachytherapy +/- EBRT from other studies.

PMID- 9264581
TI  - Expression of the farnesyltransferase beta-subunit gene in human ovarian
      carcinoma: correlation to K-ras mutation.
AB  - The ras signaling protein requires a posttranslational modification to localize
      it to the inner surface of plasma membrane. In this state it can behave as a
      signal transduction mediator. Farnesyltransferase plays an important role in this
      posttranslational processing of ras by attaching a farnesyl group to the cysteine
      of the ras C-terminal tetrapeptide. In this study, we investigated the
      relationship of K-ras expression and mutation with farnesyltransferase beta
      subunit expression in 20 ovarian tumors (17 carcinomas and 3 low malignant
      potential tumors) and 4 normal ovaries. The expression level of mRNA was
      determined by using quantitative PCR and mutation analysis was performed by
      direct cDNA sequencing. K-ras mutations were found in 1 of 3 low malignant
      potential tumors and in 4 of 17 carcinoma cases. K-ras mRNA overexpression was
      found in 1 of 3 low malignant potential tumors (one with mutated ras) and in only
      1 of 17 carcinoma cases. Farnesyltransferase beta-subunit mRNA overexpression was
      found in 2 of 3 low malignant potential tumors and in 7 of 17 carcinoma cases.
      Interestingly, all K-ras mutation cases showed farnesyltransferase beta-subunit
      overexpression. These findings suggest that there may be a direct relationship
      between K-ras (ras dysfunction) mutation and expression of farnesyltransferase
      beta-subunit gene.

PMID- 9264582
TI  - Comparison of 1997 Medicare relative value units for gender-specific procedures:
      is Adam still worth more than Eve?
AB  - BACKGROUND: On January 1, 1992, Congress implemented a Medicare payment system
      based on relative value units (RVUs). The total RVU (which is made up of work,
      practice, and malpractice RVUs) is multiplied by a dollar conversion factor to
      set the reimbursement for all procedures covered by Medicare. In a previous
      study, we found that significant gender bias exists in Medicare reimbursement for
      female-specific services. Recently, HCFA approved increases (beginning January
      1997) in the work RVU for many gynecologic procedures. This study was undertaken
      to compare work and total RVUs for gender-specific procedures effective January
      1, 1997. METHODS: Using the May 1996 Federal Register, we compared work and total
      RVUs for 24 pairs of gender-specific procedures. The groups were matched so that
      the amount of work and level of difficulty would be similar, if not identical. We
      validated our selection of procedures for comparison by also evaluating the
      average time required to perform these procedures. RESULTS: Comparison of work
      RVUs for the 24 paired procedures revealed that in 19 cases (80%), male-specific
      procedures had a higher RVU; in 3 cases (12%), female-specific procedures were
      higher; and in 2 cases, there was no difference. On average, work RVUs were 49%
      higher for urologic procedures than for gynecologic procedures. Comparison of
      total RVUs revealed that in 20 cases (83%), urologic procedures had a higher
      total RVU and in 3 cases (12%), gynecologic procedures were higher. On average,
      male-specific surgeries are reimbursed at an amount which is 37% higher than that
      for female-specific surgeries. CONCLUSION: Recent increases in work RVUs for many
      gynecologic procedures have resulted in improved reimbursement. However, even
      with these improvements, significant gender bias still exists in the Medicare
      reimbursement of female-specific procedures. This gender bias is further
      magnified as more private insurance carriers use the system to set reimbursement.

PMID- 9264583
TI  - Pure alveolar rhabdomyosarcoma of the corpus uteri: description of a case with
      increased serum level of CA-125.
AB  - We report a morphological and immunohistochemical study of a case of pure
      alveolar rhabdomyosarcoma of the uterus in an 80-year-old woman. The diagnostic
      clues were the characteristic "alveolar" pattern of growth, the evidence of cross
      striations in strap or elongated cells with abundant eosinophilic cytoplasms, the
      presence of multinucleated cells with peripherally placed "wreathlike" nuclei,
      and the expression of muscular antigens by the tumor cells. A thorough sampling
      of the tumor excluded areas of other types of heterologous or homologous sarcomas
      or the presence of coexisting adenoma or carcinoma. The other immunohistochemical
      data showed a high proliferative rate as well as a high rate of p53
      overexpression in the small poorly differentiated rhabdomyoblasts. Interestingly,
      the large differentiated rhabdomyoblasts expressed CA-125, the antigenic
      determinant of nonmucinous epithelial ovarian tumors. The clinical course was
      very aggressive: the patient died 5 months after surgery because of disease
      progression. The pertinent literature is discussed.

PMID- 9264584
TI  - Cervical carcinoma metastatic to the brain.
AB  - Brain metastases from cervical cancer are uncommon and are usually considered
      incurable. Characterization of presentation and a consensus on standard effective
      treatment have not been published. We present a case in which long-term disease
      free survival has been achieved by surgical resection of a solitary brain
      metastasis with postoperative whole brain radiation. The world literature is
      examined and discussed in relation to this experience.

PMID- 9264585
TI  - Villoglandular adenocarcinoma of the cervix: a report of three cases and review
      of the literature.
AB  - Villoglandular adenocarcinoma of the cervix is a distinct histologic type of
      cervical cancer. Fewer than 60 cases have been reported in the literature.
      Previous reports suggest that, due to the highly favorable prognosis of this rare
      histologic type of cervical cancer, conservative surgical therapy with cervical
      conization or extrafascial hysterectomy alone may be undertaken. In this series,
      three cases of villoglandular adenocarcinoma of the cervix are described.
      Preoperatively in each case, the cancer was confined to the cervix and histologic
      well-differentiated villoglandular adenocarcinoma of the cervix was confirmed.
      Extended hysterectomy was performed in all cases. In one case, residual invasive
      endocervical adenocarcinoma was noted. Careful review of the histologic
      characteristics of these tumors is needed when deciding if these patients can be
      managed with conservative therapy.

PMID- 9264586
TI  - Posterior exenteration through groin incision in a patient with stage III vulvar
      carcinoma.
AB  - During performance of bilateral groin incisions, an abdominal incision and a
      colostomy has the potential risks of devascularization of the lower abdominal
      wall and infection. A patient with locally advanced vulvar carcinoma requiring a
      posterior exenteration is presented. The posterior exenteration was performed by
      developing an abdominal skin flap from the groin incisions. This approach offers
      adequate exposure and a unique solution to the potential problems associated with
      combining an abdominal skin incision with bilateral groin incisions and end
      descending sigmoid colostomy. In addition, this approach may be cosmetically more
      acceptable.

PMID- 9264587
TI  - Paclitaxel in advanced ovarian cancer: too much optimism?

PMID- 9264588
TI  - Prediction of residual neoplasia in hysterectomy specimens among women previously
      treated by cervical conization.

PMID- 9264589
TI  - Unexpected incidence of neurotoxicity.

PMID- 9264590
TI  - [What is your diagnosis? Costo-chondritis obscured by x-ray double-exposure].
AB  - The case of a 64 years old female patient with chest pain, dizziness and abnormal
      chest x-ray is presented. The different diagnostic possibilities are discussed.
      The final assessment in the case was a double radiographic exposure of the chest
      film confusing the clinical picture.

PMID- 9264591
TI  - [Ethical guidelines for the negotiation of medical plans in the age of
      coordinated care].

PMID- 9264592
TI  - [Personal destiny: determination, will, and action].

PMID- 9264593
TI  - [Basic principles of reconstructive surgery of the outer nose].

PMID- 9264594
TI  - [Complications of endonasal surgery of the paranasal sinuses. Incidence and
      strategies for prevention].
AB  - BACKGROUND: Complications of endonasal surgery continue to occur despite improved
      optical instruments and surgical techniques. The clinical course of our patients
      was analysed to develop strategies for a safer surgical technique. PATIENTS: At
      the Department of Otorhinolaryngology, Head and Neck Surgery, University of Kiel,
      1172 patients (2010 operated sides) were treated between 1986 and 1990 for
      chronic sinusitis by endonasal paranasal sinus surgery. RESULTS: The following
      intraoperative complications were observed: dural injury in 0.8% of the patients
      (0.5% of the operated sides), retrobulbar hematomas in 0.25% of the patients
      (0.15% of the operated sides), and hemorrhages requiring transfusion in 0.8% of
      the patients (0.5% of the operated sides). No injuries of the orbital muscles,
      the optic nerve, or the carotid artery were observed. Endonasal
      dacryocystorhinostomy was performed in 195 patients, 15% of whom had previously
      had paranasal sinus surgery. Endonasal frontal sinus surgery type II or III was
      performed in 40 patients between 1953 and 1993. A past surgical history-mostly
      extranasal frontal sinus surgery according to Ritter-Jansen and Lathrop-was found
      in 80% of these patients. Of 12 mucoceles of the frontal sinuses, 10 had
      developed after extranasal procedures whereas two developed spontaneously.
      CONCLUSION: This analysis shows that the occurrence of severe intraoperative
      complications can be minimized if certain guidelines are followed. When operating
      in an anterior-posterior direction, one should, to the extent possible, preserve
      the ethmoid bulla and the middle turbinate as anatomical landmarks as long as
      possible. The ethmoid bulla indicates the upper margin of the infundibulum even
      after removal of the uncinate process. There is no danger of injuring orbital
      structures if one identifies the maxillary ostium on a line going parallel to the
      floor of the main nasal cavity from the lowest point of the bulla in a posterior
      direction. The anterior wall of the bulla also forms the posterior wall of the
      frontal recess. As long as it is preserved it protects the base of the skull when
      identifying the frontal ostium. The endonasal enlargement of the frontal sinus
      ostium as a frontal sinus drainge type II or III is safe if the spina nasalis
      frontalis and the base of the frontal sinus are removed with a drill in an
      anterior direction. When opening the ethmoid sinus in an anteroposterior
      direction, an additional imaginary line through the ethmoid bulla running
      parallel to the floor of the nasal cavity and therefore also to the base of the
      skull should be observed and not crossed cranially. The medial blade of the
      middle turbinate represents an important guide to protect the rima olfactoria. It
      must therefore be preserved. Exposure of the sphenoid sinus should always be
      performed transnasally near to the septum and below the sphenoid ostium but never
      through the ethmoid to prevent damage of the optic nerve or the carotid artery.
      Observation of these guidelines and anatomical structures will prevent mistakes
      and wrong approaches in the context of endonasal surgery.

PMID- 9264595
TI  - [Inverted papilloma of the nose and paranasal sinuses--diagnosis, surgical
      procedure and studies of cytokeratin profile].
AB  - BACKGROUND: Inverted papilloma is a benign sinunasal tumor, characterized by
      aggressive nature and tendency to recur. This tumor also has a significant
      malignant potential (10%). In spite of extensive research in the past the origin
      of inverted papilloma is not known. METHODS: A retrospective analysis of the
      clinical data of 28 patients suffering from inverted papilloma of the nose and
      paranasal sinuses with regard to symptoms, clinical examination, computed
      tomography findings, and operative management was performed. Furthermore,
      immunohistochemical examinations of the cytokeratin profile of 12 specimens were
      carried out. RESULTS: The most presenting symptoms were unilateral nasal
      obstruction (17.61%) and rhinorrhea (7.25%). Polyposis was seen endoscopically in
      19 cases (68%), so that in many patients in inverted papilloma became suspicious
      in the CT scan. The surgical therapy was dictated by the extent of the tumor, so
      that the tumor was treated by lateral rhinotomy (n = 17), midfacial degloving (n
      = 5), endonasal endoscopic surgery (n = 5), and craniofacial resection due to an
      infiltration of the frontal skull base (n = 1). An immunohistochemical analysis
      of the cytokeratin profile revealed for the first time that the inverted
      papilloma, when compared to the normal surface epithelium of the nasal cavity and
      the paranasal sinuses, exhibits increased expression of cytokeratin 5, typical
      for basal cells, and cytokeratin 13, typical for squamous epithelial cells.
      CONCLUSIONS: Based on our results we recommend that the endonasal approach is
      reliable for processes restricted to the middle nasal meatus and the anterior and
      middle ethmoid cells. Inverted papilloma of the frontal sinus, retrobulbar and
      supraorbital ethmoid cells, and laterocaudal parts of the maxillary sinus should
      be resected via lateral rhinotomy or midfacial degloving. The findings of
      immunohistochemical examinations suggest that inverted papilloma is derived from
      a cytokeratin 5-immunoreactive cell of the basal layer of the mucosa.

PMID- 9264597
TI  - [Cinematographic functional diagnosis of swallowing after plastic reconstruction
      of large tumor defects of the mouth cavity and pharynx].
AB  - BACKGROUND: Reestablishing good swallowing function after resection and
      reconstruction of head and neck tumors is very important for our patients' well
      being. Today many different surgical concepts for reconstruction after tumor
      surgery are in common use. It is necessary to establish a good diagnostic
      procedure for postoperative assessment of the swallowing function. High-speed
      cineradiography at a minimum of 50 frames per second is well established for
      evaluating swallowing problems in head and neck patients. METHODS: Thirty-six
      patients divided into three groups were examined using high speed cineradiography
      after surgical treatment of pharyngeal and oral cavity cancer. Group 1 (n = 12)
      included patients with a subtotal or total tongue resection and reconstruction
      with infrahyoid myofascial flap and jejunal flap; Group II (n = 8), patients with
      total resection of the oropharynx soft palate and velum and reconstruction with a
      free radial forearm flap; Group III (n = 15), patients with total
      laryngopharyngektomy and reconstruction with jejunal flap and siphon and with or
      without repair of the digastric muscle. RESULTS: Group I: All patients with
      tongue reconstruction were able to swallow normally from the oral cavity into the
      pharynx. All patients had normal bolus propulsion because of a good tongue volume
      and tongue motility. There was only one case of aspiration after total
      glossectomy with the larynx left in place. All patients could swallow with the
      head and neck in a normal position. Group II: All patients with reconstruction of
      the soft palate and velum were able to initiate proper bolus propulsion without
      nasal regurgitation or rhinolalia aperta. Only one patients suffered from chronic
      aspiration after hemiresection of the oropharynx and hypopharynx. Group III: All
      patients with pharynx reconstruction had no problems with bolus transfer through
      the reconstructed pharynx. Aspiration into the reconstructed pharynx was a major
      problem for those patients without repair of the digastric muscle (5/8 = 63%).
      Better results were observed in the patients who underwent repair of the
      digastric muscle. There was only one case (13%) of aspiration. CONCLUSIONS: By
      using high-speed cineradiography it is possible to make a detailed description of
      the swallowing function after extensive surgical treatment of pharyngeal and oral
      cavity cancer. We think that high-speed cineradiography is a very sensitive
      diagnostic procedure capable of detecting all functional aspects of swallowing.
      High-speed cineradiography should be one of the standard diagnostic studies
      performed surgery of the oral cavity and pharynx.

PMID- 9264596
TI  - [Globus pharyngis and gastroesophageal equivalents].
AB  - BACKGROUND: Globus sensation is a phenomenon of largely unknown etiology.
      Dyskinesia of the upper esophageal sphincter is quite often evident without
      pathological ENT findings elsewhere. PATIENTS AND METHODS: One hundred ten
      patients were examined in a interdisciplinary approach. The investigation
      included videofluoroscopy, esophagogastroduodenoscopy with biopsy,
      pharyngoesophageal computer manometry, and esophageal pH monitoring. One hundred
      five cases were evaluated. RESULTS: In 13 cases (12.4%) there was no evidence for
      any organic or functional disorder. In 92 cases (87.6%) abnormal findings were
      seen with two constellations being predominant. These are primarily inflammatory
      lesions in the stomach or the duodenum in 69.5% of all patients (73/105)
      associated with helicobacter pylori colonization in 58% (42/73) as well as ulcera
      and/or erosions in 8.2% (6/73). Concurrent disorders of the lower esophageal
      sphincter play the second role. Sixty-one point nine percent of all patients
      (65/105) had an hiatal hernia, with gastroesophageal reflux in 36.9% (24/65). In
      21.5% (14/65) a reflux esophagitis was evident. A cardiac sphincter insufficiency
      was found in 6.7% (7/105). CONCLUSIONS: Based on these findings a
      gastroenterologic diagnosis is recommended in all patients with globus sensation
      as the symptom may be associated with corresponding disorders.

PMID- 9264598
TI  - [Possible indications for temporalis muscle flaps in plastic-reconstructive
      surgery of the head and neck].
AB  - BACKGROUND: In reconstructive plastic surgery, the temporalis muscle has proven
      to be a reliable and versatile flap for a wide field of indications. The
      temporalis muscle is a flat, fanshaped muscle with a generous blood supply and
      innervation from the trigeminal nerve. METHODS AND RESULTS: Based on our own
      experiences in a total of 25 cases (12 cases involving muscle transposition for
      mouth reanimation, six cases involving stabilisation of a duraplasty including
      protecting the internal carotid artery in one case, four cases involving
      reconstruction of the orbital floor or the base of the skull, and three cases
      involving recontouring the lateral face) and a review of the literature we give
      an up-to-date overview of the different indications for the temporalis muscle
      flap. These include: a) treatment of facial nerve paralysis, b) recontouring of
      the lateral face, c) reconstruction of skull base, orbita, and oropharynx, d)
      stabilization of duraplasty, e) protection of internal carotid artery, f) in
      temporomandibular joint surgery, and g) for obliteration in ear surgery.
      CONCLUSION: Because of the wide range of indications, the temporalis muscle flap
      remains a versatile and important tool in plastic reconstructive surgery.

PMID- 9264599
TI  - [Transplantation of in vitro cultured cartilage materials: characterization of
      matrix synthesis].
AB  - BACKGROUND: Recently a three-dimensional model for the formation of cartilage in
      vitro was developed. The aim of this study was to investigate the amount and
      quality of newly synthesized matrix after graftig in vitro engineered cartilage
      into athymic nude mice. MATERIAL AND METHODS: Group I received transplants
      consisting of human chondrocytes, agarose, and E 200 (a bioabsorbable polymer
      fleece that offers mechanical stability. Ethicon Inc). Group II received
      chondrocytes and agarose only. At intervals of six, 12, and 24 weeks after
      subcutaneous transplantation we used azan blue staining and antibodies against
      collagen type I, collagen type II, and chondroitin-4sulfate to characterize the
      matrix synthesis. A quantitative analysis was performed using the computer image
      analyzing software photoshop (Adobe Inc). RESULTS: In group I, the amounts of
      newly synthesized cartilage specific collagen type II and chondroitin-4 sulfate
      increased progressively. Twenty-four weeks after transplantation, these amounts
      were comparable to the original human cartilage from which the chondrocytes were
      derived. Collagen type I was detected only in small quantities in the periphery
      of the transplants. Gross examination revealed sufficient mechanical stability
      and unremarkable changes in size and form. In contrast to this, group II
      transplants showed markedly smaller amounts of cartilage specific matrix
      components as collagen type II and chondroitin-4 sulfate and at the same time
      greater amounts of collagen type I. It was found both in the periphery and in
      central parts of the transplants. There was a remarkable loss of volume in all
      transplants and mechanical stability was poor. CONCLUSIONS: The absorbable cell
      carrier E 200 not only offers mechanical stability to in vitro engineered
      cartilage but also had a positive effect on the development of cartilage in our
      experiments. In conclusion, in vitro engineered cartilage is a promising pathway
      for the replacement of cartilage defects.

PMID- 9264600
TI  - [Realistic imaging of cell systems using confocal laser scanning microscopy
      exemplified by 3-dimensional chondrocyte culture].
AB  - BACKGROUND: We have developed a three-dimensional model for tissue engineering of
      cartilage. Chondrocytes were isolated and first multiplied in conventional
      monolayer cultures. Then the cells are seeded with or without agarose on special
      absorbable scaffolds that provided stability and enabled three-dimensional cell
      distribution of the tissue-engineered cartilage. The aim of the study was to
      investigate the possibility of avoiding agarose in tissue engineering because of
      the potential risk of causing an inflammatory process in later human
      implantation. METHOD: For the first time we investigated cell distribution
      combined with vitality directly in the cell carrier under the conditions
      described by using confocal laser-scanning microscopy. Working with unfixed
      cells, this method enables the reconstruction of three-dimensional cell cultures
      with suitable cell markers that closely simulates the physiologic situation,
      thereby exceeding each other method. RESULTS: It was evident that agarose had no
      positive effect on cell distribution and vitality. CONCLUSION: Further
      experiments concerning the effect of agarose on synthesis of cartilage-specific
      matrix are in progress.

PMID- 9264601
TI  - [Primary intra-meatal invasion of meningioma into the left meatus acusticus
      internal in a 49-year-old woman].
AB  - BACKGROUND: Meningiomas originating in the internal auditory meatus are rare and
      have been reported in only 12 cases. PATIENT: We report about another case, which
      showed primarily the symptoms of sudden hearing loss and diagnostic signs of an
      intrameatal acoustic neuroma. The ABR interpeak latency IV was prolonged. The
      tumor was detected by MRI scan with gadolinium contrast enhancement and resembled
      the features of an intrameatal acoustic neuroma. RESULTS: The tumor was removed
      via a middle fossa approach with preservation of hearing and facial nerve
      function. Histological examination however revealed a meningioma originating from
      the internal auditory meatus. CONCLUSIONS: Contrast enhancing intrameatal tumors
      are most often acoustic neuromas. However even despite subtile audiological and
      neurotological examination and sophisticated imaging techniques they cannot be
      differentiated clinically from meningiomas at this location. Removal of the
      intrameatal tumor via a middle fossa approach seems to be the best surgical
      approach to preserve hearing and facial nerve function.

PMID- 9264602
TI  - [Reimbursement budgets and treatment demands require cost saving--a short
      operations day as a possible solution in the hospital].
AB  - BACKGROUND: Implementation of case related budgeting (similar to diagnosis
      related groups) has forced hospitals into more cost efficient management
      particularly with respect to surgery. Efforts to increase efficiency are
      concentrated on the labor intensive organization of the surgical ward. Operations
      of short duration are a major focal point. An analysis of the organizational
      structure of our hospital showed that significant improvement in operating
      theater management and utilization can be achieved in order to improve
      efficiency. A new pilot project was tested for economic efficiency. METHODS: On
      eleven specified surgery days (129 patients) only short operations with a
      duration of less than 20 min were allowed (tonsillectomy, adenectomy, etc.). On
      each day 15 operations were performed in one operating room with two
      anesthesiology teams and one surgery team. This type of "short-operation day" was
      compared with a "regular" surgery day with two operating rooms, two
      anesthesiology teams, and two surgery teams. Efficiency, complication rates,
      economic outcome, and patient satisfaction were assessed. RESULTS: Due to
      reduction of staff and a more efficient organization, we were able to reduce the
      costs for staff and the operating theater maintenance from DM 378,20 to DM 243,90
      for each operation. Additionally, only one operating room was required instead of
      two. Complication rates (postoperative bleeding) were lower than before and
      patient acceptance and satisfaction was remarkable. CONCLUSIONS: Economic
      efficiency of short operations could be increased by organizational
      restricturing. The quality of the operations and the patients' satisfaction did
      not decrease.

PMID- 9264603
TI  - [Different forms of microtia depicted on a Flemish altar piece of the 15th
      century in Ghent].
AB  - An alterpiece created by the master of the Wenemaer Triptych, a painter from the
      Flemish school in the second half of the 15th century, is displayed in the Museum
      for Fine Arts of Ghent. The triptych comprises five parts with scenes of the life
      of Christ. The artist painted all the faces with portrait-like features,
      including anatomical details of the auricles. My medical attention was attracted
      to deformed auricles depicted in nine of the 41 persons from all age groups.
      There are good arguments to support the hypothesis that persons with various
      types of microtia had been models for the painter.

PMID- 9264604
TI  - [Speech disorders in ENT practice].
AB  - The most frequent speech and language disorders which ENT doctors are confronted
      with are generally known to be and presented as: delayed speech and language
      development, dystalia, dysglossia, rhinolalia, dysarthria, and verbal fluency
      disorders (stuttering, cluttering). The diagnostic portion in comparison to the
      therapeutic part is always greater and quite different. The close cooperation
      with representatives of phoniatrics and pedaudiology, as well as logopedics and
      other specialities such as neurology, and internal medicine is highly necessary.

PMID- 9264605
TI  - [Interesting case no. 1. Cerebrospinal fluid fistula of the right nasal skull
      base].

PMID- 9264606
TI  - 5th European Meeting on Psychosocial Aspects of Genetics. Rome, Italy, September
      26-28, 1996. Abstracts.

PMID- 9264607
TI  - Triterpenes and triterpenoid saponins from Mussaenda pubescens.
AB  - Two novel triterpenoid saponins, named mussaendosides U and V, together with one
      known saponin and four known triterpenes were isolated from the aerial parts of
      Mussaenda pubescens (Rubiaceae). The structures were determined on the basis of
      chemical analysis ad spectral methods. All these compounds were identified for
      the first time from the genus Mussaenda.

PMID- 9264608
TI  - Jennisseensosides C and D, biologically active acylated triterpene saponins from
      Silene jenisseensis.
AB  - We previously reported the isolation and structure elucidation of a new trans-p
      methoxycinnamoyl triterpene-saponin along with its cis-p-methoxycinnamoyl isomer
      as an inseparable mixture from the roots of Silene jenisseensis. In a continuing
      study on this plant, two additional new acylated triterpene-saponins were
      obtained as an inseparable mixture. Their structures have been established by
      chemical means and spectroscopic methods including 1D and 2D homonuclear and
      heteronuclear correlation NMR spectroscopy as 3-O-[beta-D-galactopyranosyl-(1-
      >2)-beta-D-glucuronopyranosyl]-28 -O-[{alpha-L-rhamnopyranosyl-(1-->2)}-{4-O
      trans-p-methoxycinnamoyl++ +}-beta-D-fucopyranosyl] quillaic acid and its cis
      isomer, respectively. They showed a significant enhancement of the granulocyte
      phagocytosis in vitro.

PMID- 9264609
TI  - Cytotoxic lignans from Formosan Hernandia nymphaeifolia.
AB  - A new dibenzylbutyrolactone lignan, (--)-6-hydroxyyatein, along with two new
      furanoid lignans, (--)-hernone [(2R,3S,4R)-(--)-3-hydroxymethyl -4-(3",4",5"
      trimethoxybenzoyl)-2-(3,4-dimethoxyphenyl) tetrahydrofuran] and (--)-nymphone
      [(2R,3S,4R)-(--)-3-hydroxymethyl-4-(3",4",5"-trimethoxybenzoyl)-2- (3,4
      methylenedioxyphenyl)tetrahydrofuran], have been isolated and characterized from
      the trunk bark of Formosan Hernandia nymphaeifolia. The structures of these
      compounds were determined by means of spectral analyses. These three lignans
      exhibited cytotoxic activities against P-388, KB16, A549 and HT-29 cell lines.

PMID- 9264610
TI  - Bibliography. Current world literature. Nucleus and gene expression.

PMID- 9264611
TI  - Proceedings of the 11th International Symposium on Affinity Chromatography and
      Biological Recognition.

PMID- 9264612
TI  - Detection of inosine in messenger RNA by inosine-specific cleavage.
AB  - Double-stranded RNA adenosine deaminases catalyze the conversion of adenosine to
      inosine within double-stranded RNA. A few candidate biological substrates for
      these enzymes have been discovered by noticing discrepancies between genomic and
      cDNA sequences. Toward the goal of finding a systematic approach to identify new
      deaminase substrates, we developed a method to cleave RNA specifically after
      inosine and an amplification strategy to identify the cleavage sites. We tested
      our method on a candidate substrate, the messenger RNA for glutamate receptor
      subunit B (GluR-B). We detected cleavage of the endogenous GluR-B message from
      rat brain at two known RNA editing sites, thus providing the first direct
      evidence for the presence of inosine at these sites. The described method will
      facilitate the mapping of inosines within RNA and, most importantly, will provide
      a way to identify new deaminase substrates.

PMID- 9264613
TI  - [Discussion of the pulmonary artery catheter].

PMID- 9264614
TI  - [Effectiveness of pulmonary artery catheterization in the critically ill patient-
      attempt at evaluating current status].
AB  - Pulmonary artery catheterization is currently used for more than 25 years for the
      hemodynamic monitoring of critically ill patients. As for every monitoring
      technique, its indication is based on the goal, that knowledge of the obtained
      additional hemodynamic parameters may lead to an optimization of therapy and
      thereby to an improvement in patients'outcome. Despite of the presence of
      clinical studies which documented changes in therapy following such extended
      monitoring, there is no clear proof for a positive effect on patients' mortality.
      While some of the available studies showed a benefit by pulmonary artery
      catheterization, others did not or even demonstrated a negative effect. However,
      no study fulfilled the scientific requirements which enables to make a statement
      to the effectiveness of pulmonary artery catheterization by objective criteria.
      The purpose of this review article is to summarize the currently available
      literature with regard to the effectiveness of pulmonary artery catheterization
      in the critically ill patient.

PMID- 9264615
TI  - [Results of autologous blood donation in orthopedic hip and knee joint
      replacement].
AB  - OBJECTIVE: This study was undertaken to investigate the efficiency of autologous
      blood donation (ABD) with regard to saving of homologous transfusion, to
      determine the reasons for exclusion from donations and the rate of incidents
      during the procedure, and to investigate the quality of autologous fresh frozen
      plasma (AFFP). METHODS: During an observation period of 4.5 years, all patients
      scheduled for elective orthopaedic hip and knee replacement were included. A
      period of 4 years was evaluated retrospectively, and the last half year was
      evaluated prospectively. RESULTS: Among a collective of 710 patients, 55 (8%) non
      donors and 655 (92%) donors with a total number of 1592 ABD were found. Mean age
      of non-donors with hip surgery was significantly higher than that of donors (72
      vs. 64 years), the same was observed in patients with knee surgery (71 vs. 68
      years). In the hip surgery group, 11 of 338 patients were non-donors (3%),
      compared with 44 of 372 patients with knee surgery (12%). In the prospective part
      of the study, 7% of 121 patients were non-donors. Reasons for exclusion from
      donation were 5 times of medical and 4 times of organisational nature. In donors
      for hip surgery, a mean of 3.0 units was collected, compared with 1.9 units in
      donors for knee surgery. On the day before operation, mean haemoglobin
      concentrations were similar in donors and non-donors. During ABD, 11 incidents
      were observed, representing 0.69% of all ABD, 83.5% of 327 donors with hip
      surgery left the hospital without any transfusion of homologous blood, 16.5 of
      donors with hip surgery received one or more homologous transfusions, compared
      with 100% of non-donors (p < 0.001). In knee surgery, 93.3% of donors and 63.6%
      of non-donors required no homologous blood, whereas 6.7% of donors and 36.4% of
      non-donors received one or more homologous transfusions (p < 0.001). 529 of 2850
      autologous blood units (19%) were not transfused, and 19 of these units were
      rejected due to technical or organisational problems. In 97 patients with 240 ABD
      and 240 AFFP, prothrombine time, fibrinogen concentration and AT III in defrosted
      AFFP exceeded 70% of the values determined before ABD. CONCLUSION: ABD is a safe
      procedure in almost all, even elderly, patients scheduled for elective
      orthopaedic hip or knee replacement in both types of operations, ABD reduces the
      risk of homologous transfusion significantly. A number of 3-4 units is necessary
      for total hip replacement, whereas 2 units are sufficient for partial or total
      knee replacement. Haemostatic quality of AFFP meets the requirements of fresh
      frozen homologous plasma.

PMID- 9264616
TI  - [Effectiveness of autologous blood donation in coronary surgery--a retrospective
      analysis].
AB  - OBJECTIVE: This study was performed to evaluate whether autologous blood donation
      prior to coronary artery bypass graft surgery (cabg) reduces homologous blood
      requirements and the risk of homologous blood transfusion. METHODS: Within a
      period of 18 months, 633 patients undergoing cabg surgery were retrospectively
      included into the study. Non-donors were included if preoperative haemoglobin
      concentration exceeded 12.5 g%. RESULTS: According to demographic data, risk
      scores of patients who donated blood (n = 201) were lower. More patients of this
      group received left internal mammary bypass grafts (63% vs. 51%; p = 0.047).
      Nevertheless, blood loss did not differ between donors and non-donors. Prior to
      blood donation, haemoglobin-concentration was significantly higher in male donors
      (n = 177) compared to female donors (n = 24) (15 +/- 1.2 vs. 13.8 +/- 1 g%; P <
      0.001). Compared to female donors, male patients donated significantly more blood
      units. The risk of homologous blood donation was significantly lower in male
      donors than in male non-donors (no homologous transfusion: 20% vs. 42%; P <
      0.0001; Odds Ratio: 0.34; 95% confidence-interval: 0.23-0.52). Accordingly,
      homologous blood requirements were lower in male donors (0.9 +/- 3.4 vs. 1.6 +/-
      3.6 blood units; P = 0.02). Between female donors and non-donors neither the
      number of patients treated with homologous blood (no homologous transfusion: 29%
      vs. 33%, P = 1; odds ratio: 1.17; 95% confidence-interval: 0.4-3.4), nor the mean
      number of transfused homologous blood units (1.8 +/- 1.6 vs. 1.9 +/- 2.4; P =
      0.83) was different. Reactions during blood donation requiring treatment
      (bradycardia, hypotension, angina, arrhythmias) occurred more often in female
      patients (5/24 vs. 9/177; P = 0.015). CONCLUSION: In our study, autologous blood
      donation significantly decreased the risk of homologous transfusion and
      homologous blood requirements in male cabg patients. We were not able to prove
      the efficacy of autologous blood donation in female cabg patients. Due to the
      small sample size of our investigation, further prospective studies are necessary
      to answer the question whether patients with low blood volume, body weight and
      body height scheduled for cabg surgery should be excluded from autologous blood
      donation.

PMID- 9264617
TI  - [Clinical and preclinical efficacy of antimicrobial catheters].
AB  - Frequent use of polymeric material for diagnostic and therapeutic use has
      provoked an increase of so-called polymer-associated foreign body infections. The
      difficulties in correctly diagnosing catheter-related infections and the
      necessity to remove the device in case of suspected infection require preventive
      procedures in the first place. Therefore, several studies have dealt with surface
      treatment by coating with antibiotics, antiseptics and silver. Some of them
      remain in clinical trials or are already sold in the USA. Clinical failure of
      silver-sulfadiazine coated CVCs has been reported recently. Recently a
      rifampicinminocyclin-catheter has been shown to reduce efficiently material
      associated infection in preclinical and clinical studies. Most of the substances
      retained on catheter surfaces are released only in small quantities resulting in
      ineffective suppression of bacterial growth. If substantial amounts of
      antimicrobials are incorporated into the biomaterial, release pattern and killing
      efficacy of each substance group has to be determined in order to reach
      bactericidal concentrations in the environment of adherent bacteria. Killing
      kinetics of antibiotics, antiseptics and silver to bacteria are strongly
      different. On the one hand killing kinetics of microorganism due to substantial
      quantities of antiseptics are fast, on the other hand antiseptics destroy
      structures of both, bacteria and blood cells. Bactericidal concentrations of Ag
      ions show fibroblast inhibition. Antibiotics, however, show lowest toxicity due
      to the specific action to microorganisms. However, sustained release over time is
      needed to reach bactericidal concentrations, considering the slower bactericidal
      action of typical antibiotics. Development of allergic reaction is possible for
      all substances, whereas development of bacterial resistance can be prevented by
      use of antimicrobial combinations.

PMID- 9264618
TI  - [Principles of pharmacology].

PMID- 9264619
TI  - [Conversion from peridural to transdermal opiate analgesia in abdominal tumor
      pain syndrome].
AB  - In a 32 years old patient with advanced gastric cancer epidural analgesia with
      local anaesthetic and morphine via a thoracic epidural catheter was required
      because of intractable pain and intolerable side effects of intravenous morphine.
      In spite of good efficacy it was decided to remove the catheter because of
      technical problems and the risk of infection during chemotherapy. Analgesic
      therapy proceeded to non-invasive transdermal fentanyl, using an intravenous
      fentanyl pca-pump during transition. The equipotent daily dose ratio of epidural
      morphine to transdermal fentanyl was calculated as 2.25:1.

PMID- 9264620
TI  - [Hyperplasia of the lingual tonsil as an unexpected intubation obstruction in a
      preschool child].
AB  - Case report of a five year-old boy who was admitted for elective squint surgery.
      The medical history revealed some delay in his behavioural and mental development
      as well as an unspecific dysmorphic syndrome with suspected muscular weakness.
      Tonsillectomy and adenotomy have been performed six months prior to admission.
      During examination on the day before surgery, the child presented only mild
      symptoms of a subsiding upper respiratory infection. Because of the
      uncooperativeness of the child the pharyngeal inspection was not performed. On
      the day of surgery total intravenous anaesthesia was induced by injection of
      sufentanil, propofol and atracurium. Ventilation with 100% oxygen via facemask
      was uneventful. However, laryngoscopy for endotracheal intubation was impossible
      due to a massive lingual tonsillar hyperplasia. A size 2 laryngeal mask with
      flexible spiral-tubing was inserted and anaesthesia was maintained using
      continuous propofol infusion. The surgical procedure was finished after 30 min
      and the laryngeal mask was removed. The following postoperative course was
      uneventful and the child was discharged from the hospital two days later. The
      present case report demonstrates the importance of preoperative pharyngeal
      inspection prior to elective endotracheal intubation and the possibility of
      unexpected difficult airway management by the laryngeal mask.

PMID- 9264622
TI  - [Palliative care in non-oncological diseases].

PMID- 9264621
TI  - [Primary care reform in Spain: between self-criticism and neoliberal proposals].

PMID- 9264623
TI  - [Cost analysis of nursing home visits to immobilized patients. Approach to the
      efficiency study].
AB  - OBJECTIVES. MAIN: To analyze total costs of the nursing home visit to immobilized
      patients. SECONDARY: To know the kind of nursing care according to the health
      problem; to determine the interventions made in each visit; to determine how many
      time do the nurses pass in each home visit. DESIGN: Observational cross-sectional
      study. It were revised the epidemiological card index to obtain the following
      variables: age, sex, service inclusion motive, caregiver, number of visits,
      intervention in each visit, and time of displacement. SETTING: Primary Health
      Care Center. PATIENTS: It were studied 165 patients enclosed in attendance to
      immobilized patients service. RESULTS: The mean of visits made per patient was
      3.8. Interventions made to most individuals were: feeding habits education
      (42.4%); physical activity stimulation (40.6%) and security measures counselling
      (28.48%). Total time per visit is 33.26 minutes. CONCLUSIONS: Attendance time is
      the third part of total time, so it is important to mark the need to organize the
      work in order to exploit to the full the time of each intervention. The mean
      total time is noticeably lower to other similar studies, anyway each visit cost.

PMID- 9264624
TI  - [Relationship between family perception and alcohol consumption].
AB  - OBJECTIVES: To establish the prevalence of alcohol consumption and dependence,
      and its relationship to perception of family function. DESIGN: Descriptive,
      crossover study. SETTING: Urban area. Jumilla Health Centre (Murcia).
      PARTICIPANTS: 434 Health Service users were surveyed. INTERVENTIONS: Demographic
      data, determination of alcohol consumption, CAGE and APGAR questionnaires.
      MEASUREMENTS AND MAIN RESULTS: There was a high prevalence of alcohol consumption
      (77%) and excessive consumption (22.9%). Excessive alcohol consumption was mainly
      among men and active agrarian workers. The relationship between alcohol
      consumption and family dysfunction was not significant, but was significant
      between CAGE and family dysfunction. CONCLUSIONS: Despite the high prevalence of
      alcohol consumption, family dynamics are not usually changed significantly. This
      only happens in cases of alcohol dependency syndrome.

PMID- 9264625
TI  - [Validation of a questionnaire for the diagnosis of urinary incontinence].
AB  - OBJECTIVE: To validate a questionnaire applied in the Primary Care (PC) clinic
      which enables urinary incontinence (UI) and its different types to be diagnosed.
      DESIGN: A descriptive crossover study. SETTING: A Urodynamics hospital out
      patients clinic. PARTICIPANTS: Patients referred from PC to be tested for UI by
      Urodynamics. INTERVENTION: A self-filled questionnaire prior to the Urodynamics
      test to give a rough idea of the type of UI. Analysis of patients'
      characteristics and the internal validity of the questionnaire by comparing it
      with the Urodynamics test. MEASUREMENTS AND MAIN RESULTS: The sample was 59 men
      and 432 women. For the rough diagnosis of UI caused by straining in women, a five
      question survey had a positive predictive value (PPV) of 77.2% for four
      affirmative replies, which went up to 83% if maximum exterior flow was included.
      For the UI group arising from anticholinergic treatment, a four-question survey
      had low PPV (57.6%), but this figure went up to 85.7% with a flowmeter.
      CONCLUSIONS: A questionnaire to study the type of UI, along with further tests,
      approached the aetiological diagnosis of incontinence in women. A Urodynamics
      study, however, always needs to be performed on men.

PMID- 9264626
TI  - [Effectiveness of brief medical counseling to reduce drinkers' alcohol
      consumption].
AB  - OBJECTIVE: To evaluate the effectiveness of medical counselling in reducing
      alcohol consumption in male heavy drinkers. DESIGN: A controlled, randomised,
      simple-blind intervention study. SETTING: Four Primary Care teams in Area 10,
      Madrid. PATIENTS: 152 men who attended for on-demand treatment from the four
      teams and whose alcohol consumption was over 21 International Units (IU) a week.
      INTERVENTION: Brief medical counselling backed up by didactic material. Two
      questionnaires on alcohol consumption in IU, consumption habits and problems
      related to alcohol were administered, separated by an interval of between 6 and
      18 months. Non-parametric tests for paired samples (McNemar) were applied.
      RESULTS: 60% answered the second questionnaire. Neither sociodemographic nor
      health habit differences were found between those who responded and those who did
      not, except for social class. There were no appreciable differences between the
      intervention and control groups. The percentage of drinkers above 35 IU decreased
      significantly in the intervention group. CONCLUSIONS: The intervention was
      clearly effective in reducing the percentage of drinkers whose weekly consumption
      was over 35 IU.

PMID- 9264627
TI  - [A method of detection psychosocial problems at the family physician's office].
AB  - OBJECTIVE: To find the value of the Stressful Vital Events (SVE) scale for
      detecting patients with psycho-social problems and how these affect family
      function. DESIGN: A descriptive, crossover study with systematic sampling.
      SETTING: Almanjayar Health Centre. PATIENTS AND OTHER PARTICIPANTS: 202 patients
      (138 women and 64 men) who attended for on-demand consultations at two clinics
      during October and November 1994. They were selected systematically, 1 from every
      5, with under-18s eliminated. INTERVENTIONS: The GHQ, SVE and Family APGAR tests
      were self-administered. The GHQ test was used to detect psycho-social problems,
      SVE to measure stressful vital events and the APGAR family to find family
      function. MEASUREMENTS AND MAIN RESULTS: 46% (94) had psycho-social problems; 53%
      (107), positive scoring in the SVE test; and 21% (42), family dysfunction. The
      relationship between SVE and GHQ was significant (p < 0.0001), but relationships
      with the APGAR weren't. CONCLUSIONS: We consider that exploration of SVEs is a
      good way of detecting psycho-social problems.

PMID- 9264628
TI  - [Detection by a computer program of drug interactions in chronic patients. Its
      practical usefulness in a health center].
AB  - OBJECTIVES: To evaluate a computer programme which was used to detect drug
      interactions (DI) from the Long Treatment Cards (LTC) and to analyse the factors
      possibly linked to these interactions. DESIGN: An observational, descriptive
      study. SETTING: Primary Health Care: an urban Health Centre. PATIENTS: The
      reference context was 1,640 chronic patients being cared for at a nursing clinic.
      We selected 141 cases at random by taking 10 LTCs from each list. (Alpha risk =
      0.05; Confidence Interval = 0.05). RESULTS: The sample was mainly feminine (2:1),
      with an average age of 67. The most common diagnosis was Diabetes or AHT. 55% had
      accumulated 4 or more medicines per card, with multiple medication most common
      among men. The programme enabled 58 drug interactions, affecting 34% of the LTCs,
      to be identified. CONCLUSIONS: Special attention should be paid to the LTCs with
      7 or more drugs prescribed because of their association with DI and NIV. The
      programme's efficacy would increase, both if the DIs were more accurately defined
      and if the programme could be computerised and applied massively to chronic
      treatments.

PMID- 9264629
TI  - [Xerostomia: a simple undesired effect?].

PMID- 9264630
TI  - [Etiological factors in carpal tunnel syndrome].

PMID- 9264631
TI  - [Hysteria: a hundred years later].

PMID- 9264632
TI  - [Prescription].

PMID- 9264633
TI  - [The cause of the debate on detection of hypercholesterolemia].

PMID- 9264634
TI  - [An epidemiological and social study of 127 patients with AIDS IN Aragon].
AB  - OBJECTIVE: To evaluate the profile epidemiology and social of the patient with
      AIDS in our environment and the direct relation with primary care. DESIGN: A
      descriptive, analytic and retrospective study. SETTING: The study was carried out
      in the Miguel Servet Hospital in Zaragoza. PARTICIPANTS: Patients with AIDS
      between January 1991 and june 1993 and who fulfilled the requisite diagnostic
      criteria. MEASUREMENTS AND MAIN RESULTS: Out of the 127 patients studied, 74.8%
      were male and the age was 20 to 30 years old. The transmission mechanism was
      blood way in drug addicts in 63.8% and heterosexual way in 14.8%. It was
      socioeconomic problems in 40.94%, and 69.23% of them were drug addicts. The
      familiar support were proved in 29.13% and had relation with primary care only
      15.74%. CONCLUSIONS: An increase of the incidence of AIDS is observed, prevailing
      men between 31-40 years old. The heterosexual way transmission is increasing, but
      the blood way in drug addicts is more frequently. The majority presents
      socioeconomic problems and they haven't familiar support.

PMID- 9264635
TI  - [Development of a program of prevention of drug dependence in school children].
AB  - OBJECTIVE: To promote healthy habits of behaviour among school-children so that
      they reject drug-taking and learn to identify high-risk situations. DESIGN: Quasi
      experimental study. SETTING: The Amoros private school in Carabanchel, in
      Madrid's Health District XI. PATIENTS AND OTHER PARTICIPANTS: 45 pupils from the
      eighth year of basic, aged between 13 and 14. MEASUREMENTS AND MAIN RESULTS:
      Quantitative and qualitative methods. Quantitative indicators were: number of
      students who attended the activities organised, their level of participation, the
      number of new terms, increase in knowledge. Qualitative indicators were the oral
      poll of class leaders, attainment of objectives, later evaluation of changes in
      attitude towards drug-takers and collages among the initiatives after the course.
      Drug-taking usually starts in the family context, leisure situations and peers.
      In this study isolated consumption was also detected. Most commonly consumed
      drugs were: caffeine, tobacco (mainly Virginia), alcohol occasionally, and
      cannabis. CONCLUSIONS: The type and form of drug-taking found is very similar to
      that of other, Spaniards of the same age. We found children who were not drug
      takers, but were anxious about this because they "wanted to try out drugs".

PMID- 9264636
TI  - [Evaluation of hospital emergency service attendance by patients from a basic
      health district].
AB  - OBJECTIVES: To find the sociodemographic characteristics of patients registered
      at a Health Centre (HC) who attended a hospital Casualty Department, their
      reasons for attendance, features of their use of facilities and how justified
      their attendance was. DESIGN: Descriptive study. SETTING: Urban Health Centre,
      Llefia (Badalona), between February and June, 1995. PARTICIPANTS: We used a
      questionnaire composed by the research team to survey 360 patients over 14 who
      attended the HC with a report from a Casualty Department. MEASUREMENTS AND
      RESULTS: The variables recorded were: sociodemographic characteristics, reasons
      for attending Casualty, whether they attended on their own initiative, whether
      they knew about non-hospital Emergencies, the hospital, day and time, chronic
      pathology, diagnosis and destination on discharge from Casualty, length of stay
      and justification. 53.7% were women. 57.8% were married. 95% lived with a partner
      or intimate family member, 56.9% had completed primary education and 39.4% had
      jobs. 41% suffered a chronic pathology. Monday was the busiest day and physical
      trauma was the most frequent diagnosis on discharge. We considered 54.7% of all
      the consultations non-justified emergencies. CONCLUSIONS: There is a high
      percentage of users who attend Casualty on their own initiative. Most of the
      emergencies are unjustified.

PMID- 9264637
TI  - [Effects of bioclimatology on suicides].
AB  - OBJECTIVE: To verify the influence of the weather on suicides. DESIGN: A
      retrospective descriptive study. SETTING: County of Cartagena. PARTICIPANTS: All
      the suicides recorded in the Anatomical Forensic Institute of Cartagena between
      1986 and 1993. INTERVENTIONS: Creation of a data base with the essential features
      of each suicide and all the relevant bioclimatological variables of the exact
      moment they happen. MEASUREMENTS AND MAIN RESULTS: A statistical description of
      each variable was made. The relationship between the different variables was
      defined by the Pearson chi 2 test and residual analysis. The sample data were
      compared with the population data (Neyman-Pearson and Pearson chi 2 tests), p <
      0.05. 149 suicides were recorded. These suicides occur during the day, Monday and
      Saturday being the days with the highest number of them. Distribution throughout
      the month was homogeneous: July was the month with most suicides. There was an
      age band in the second and third decades of life and a peak in elderly people.
      Our sample had 77.9% men. Retired people and housewives predominated. CONCLUSION:
      Suicides are generally influenced by meteorological factors.

PMID- 9264638
TI  - [Alcohol consumption and adolescence: a descriptive epidemiological study].
AB  - OBJECTIVES: To determine the consumption of alcoholic drinks among adolescents in
      Tres Cantos and its defining characteristics. DESIGN: A descriptive, cross
      sectional study. SETTING: State schools in Tres Cantos. PARTICIPANTS: All the
      students present (994) who had registered for the 1994-95 year. MEASUREMENTS AND
      RESULTS: A self-filled anonymous questionnaire was answered in the class-rooms of
      the schools in Tres Cantos during May 1995. The relationship between the
      variables was worked out using the computer programme EPI-INFO (version 5.01).
      73.1% of those polled consumed alcoholic drinks. There were no significant
      differences for gender. Most consumption was at the weekend. The commonest drink
      was wine and its combinations, followed by beer, rum or gin and coke, spirits and
      fizzy drinks. The CAGE test was positive in 14.1% of cases. 59.6% had got drunk
      on some occasion, 89.3% consumed alcohol for the first time before they were 16,
      which most did outside the home. There was a significant association between
      participating in religious activities and less alcohol consumption. CONCLUSIONS:
      The percentage of alcohol consumers among students is high. It is characterised
      by being similar in both sexes, starting at an early age and clear predominance
      of consumption at weekends and outside the home. Wine and its combinations is the
      commonest drink.

PMID- 9264639
TI  - [Influence of socioeconomic factors on the course and monitoring of pregnancy].
AB  - OBJECTIVE: To analyse variations in monitoring the pregnancy programme (PP) and
      in the programme's development in three population groups distinguished by their
      socio-demographic characteristics. DESIGN: An observational, descriptive and
      retrospective study. SETTING: "Occidente" Health District, Cordoba. PARTICIPANTS:
      Women who finalised their pregnancy in 1994 or 1995 (n = 415) and who lived in
      three zones distinguished geographically and socially: an Urban Area (UA), with
      an average population socially and economically and urban environment; a Marginal
      Area (MA) with a low social and economic level, high rates of unemployment and
      drug addiction, and a mixed population (gypsy and latin); and a Rural Area (RA),
      which had a rural productive way of life. MEASUREMENTS: The area of residence was
      related to the socio-demographic variables, history, drug consumption, PP
      monitoring and identified pathology. RESULTS: PP coverage reached 73.8% (CI 69.2
      77.8), Pregnant women living in the MA were younger (p < 0.001), and included
      more adolescents (p < 0.001) and more single women (p < 0.001). CONCLUSIONS:
      Poorer monitoring and adherence to the PP by the MA population could be
      confirmed.

PMID- 9264640
TI  - [Requests for microbiological diagnosis by primary care physicians in the
      Salamanca area].
AB  - OBJECTIVES: To assess requests for microbiological analysis made by Primary Care
      doctors and to evaluate the quality of the procedure by the indicator: proportion
      of contaminated urine samples. DESIGN: A retrospective crossover study of
      requests to the Microbiology Laboratory in the University Hospital of Salamanca
      during 1995. SETTING: The study covered the Salamanca Health Area, which consists
      of 35 Health Centres and a catchment population of 358,408. PATIENTS AND OTHER
      PARTICIPANTS: The requests for microbiological diagnosis and results of the
      43,317 samples processed were analysed. INTERVENTIONS: The data was distributed
      according to care level and the Area's Health Centres. MEASUREMENTS AND RESULTS:
      9,574 (22%) of the total number of samples received turned out positive, 27.4% of
      the requests originated in Primary Care (PC). The overall request rate from PC
      was 33 per 1,000 inhabitants. CONCLUSIONS: The microbiological analysis most
      frequently requested from PC is urine culture. Relationship between request and
      positives is 4 to 1.

PMID- 9264641
TI  - [Evaluation of activities and effectiveness of an asthmatic child program
      developed in primary care].
AB  - OBJECTIVE: To evaluate activities and effectiveness of a programme of attention
      to asthmatic child, defined by a proper diagnostic process and therapeutic
      intervention, by the gain of educational goals and by reduction of number of
      asthma attacks. DESIGN: A before-after study SETTING: Primary care PARTICIPANTS:
      The first 81 children attracted to the programme. Aged 5 to 13. INTERVENTION:
      Each child was periodically revised (mean time of monitoring 11 months and 24
      days: interval 7-17 months). MEASUREMENTS AND MAIN RESULTS: Intervention obtained
      significative results (p < 0.0001) in: lung function study and allergens
      detection, use of inhalatory way and peak flow meter. Asthma attacks were reduced
      (p < 0.0001): before 216, mean 2.66, SD 1.85, range 0-8; and after 117, mean
      1.44, SD 1.27, range 0-5. CONCLUSIONS: 1. A systematic and organized intervention
      from Primary Care results effective to improve quality of life in asthmatic child
      (better diagnostic, more abilities, less asthma attacks). 2. It must be stated
      new strategies for reduction of smoking at home of these children.

PMID- 9264642
TI  - [Gastric protection in the treatment with NSAIDs].

PMID- 9264643
TI  - [Study of omissions in tetanus vaccine dosage compliance. Effects of possible
      factors].

PMID- 9264644
TI  - [Antismoking intervention in chronic patients].

PMID- 9264645
TI  - [Counseling by medical visitors of primary care patients: is it scientifically
      supported?].

PMID- 9264646
TI  - [Generalized lichen nitidus. 3 case reports].

PMID- 9264647
TI  - [Problems related to dispensing of generic drugs in primary care].

PMID- 9264648
TI  - [Domiciliary hospitalization in current needs of patients with AIDS].

PMID- 9264649
TI  - [Training in communication skills for Family and Community Medicine residents].

PMID- 9264650
TI  - [Prevalence of tobacco dependence in 6 counties of Lleida].
AB  - OBJECTIVE: To find the prevalence of tobacco dependency in the population of six
      counties in Lleida and in patients with chronic diseases or vascular risk
      factors. DESIGN: Cross-sectional study. A descriptive analysis of the data.
      SETTING: Six counties in Lleida: 5 Pyrenean counties with a rural population and
      the Segria county with an urban population. PARTICIPANTS: A personal
      questionnaire covering 900 people over 15 (95% CI, 4% accuracy), chosen by
      randomised sampling, stratified for urban or rural, from the Municipal Rolls.
      MEASUREMENTS AND MAIN RESULTS: 543 individuals took part. Prevalence of tobacco
      dependency was 19.7%, higher in men (27.7%) than in women (12%) (p < 0.05).
      However, among the young there were no difference between the sexes. CONCLUSIONS:
      We found a low, in comparison with other studies, percentage of smokers in our
      sample, with a high prevalence of ex-smokers among patients with ictus or
      Coronary Disease. However, the high prevalence of smokers among the individuals
      with some cardiovascular risk factor points to the need to redouble efforts in
      health education on tobacco.

PMID- 9264651
TI  - [Changes in the sensitivity of Escherichia coli to 6 antimicrobial agents during
      the last 12 years. Group of Microbiologists of County Hospitals of Catalonia].
AB  - OBJECTIVE: To study the current state and development in the sensitivity of
      Escherichia coli during 12 years, in order to find the use of 6 antimicrobials.
      DESIGN: A descriptive study of the annual sensitivity percentages of E. coli
      strains isolated from clinical samples between 1984 and 1995. SETTING:
      Microbiology Laboratories in 15 County Hospitals in the province of Barcelona.
      PATIENTS AND PARTICIPANTS: E. coli strains, isolated from clinically significant
      samples, were studied for sensitivity against antimicrobials. MEASUREMENTS AND
      MAIN RESULTS: Cefuroxime and Gentamicin had in vitro sensibility above 94%.
      Current sensitivity of E. coli to Norfloxacin was 85%. Amoxicillin-Clavulanic
      acid maintained its sensitivity at about 80% with few variations. Ampicillin and
      Co-trimoxazole had steady sensitivity figures, always below 50 and 70%,
      respectively. CONCLUSIONS: Progressive decrease in the sensitivity of E. coli
      strains to Norfloxacin was observed. There was excellent sensitivity to
      Cefuroxime and Gentamicin.

PMID- 9264652
TI  - [Changes in the use of antibacterial agents in Catalonia, Impact of new marketed
      drugs].
AB  - OBJECTIVE: Due to the high morbidity of bacterial illnesses, there have been a
      lot of studies to assess the use of antibacterials. These studies usually focus
      on a small sample, whereas in the present study both the development of the use
      of antimicrobials in non-hospital care throughout Catalonia, and the extent to
      which new medicines are used, are examined. DESIGN: A retrospective,
      observational study. SETTING: Catalonia. MATERIAL AND METHODS: Using the data
      supplied by the pharmacy data base of the Catalan Health Service in DHD for 1992
      1995, analyses were made of the development in the use of the different
      antibacterial subgroups, the effect of using new medicines and their impact on
      similar older antibacterials. MAIN RESULTS: The overall number of antibacterials
      taken in Catalonia remained fairly stable at high levels. CONCLUSIONS:
      Antibacterials are widely used. Three is a tendency to substitute newly marketed
      medicines for traditional medicines. A more prudent attitude should be adopted
      when starting antibacterials treatments and choosing the most suitable
      antibiotics for non-hospital care.

PMID- 9264653
TI  - [Problems of diagnosis of pulmonary tuberculosis. The case of the border region
      of Chiapas (Mexico)].
AB  - OBJECTIVE: To analyze critical factors in the diagnosis of pulmonary tuberculosis
      at both the primary and secondary levels, in the Border Region of Chiapas,
      Mexico. DESIGN: A crossover study (from March to September, 1994) PARTICIPANTS:
      Patients with chronic cough (n = 221) who sought care in the Out-patient
      Department of the only second level care hospital available in the region for the
      uninsured population. Each subject was interviewed, three sputum specimens were
      requested and the clinical charts reviewed. MEASUREMENTS AND MAIN RESULTS: Fourty
      four patients were found positive for pulmonary TB of which six came to the
      hospital for initial care. 38 had already been seen in a primary care setting. Of
      those 38 only two had been diagnosed previously by acid fast smear. At the
      hospital level, the underdiagnosis of TBP was 9%. CONCLUSIONS: The quality of
      care with regard to the diagnosis of pulmonary tuberculosis needs to be improved
      at both the primary and hospital levels. Health workers need to be sensitized to
      the symptomatology and trained to request sputum smears when indicated. The
      general population also needs to be educated with regard to pulmonary
      tuberculosis so as to demand better services.

PMID- 9264654
TI  - [Extent of the use of systemic anti-infective agents in a rural health area in
      Asturias. Comparison of the years 1994 and 1995].
AB  - OBJECTIVE: To establish how widely used systemic drugs against infection were in
      1994 and 1995. To compare the interannual variation and evaluate whether this is
      consistent with CFyT interventions to improve prescription habits. DESIGN:
      Comparative before-and-after study without a control group. SETTING: A rural
      Health Area with 57,536 inhabitants, 24.01% of whom were over 65. PARTICIPANTS:
      All the general practitioners in the Primary Care public network in this Health
      Area who prescribed medicines charged to the SNS (National Health Service) in
      1994 and 1995. MEASUREMENTS AND MAIN RESULTS: All the prescriptions billed to the
      SNS were processed. Prevalence of use was measured by the variable N(o)DDD/1,000
      inhabitants per day. Annual values and variations were obtained for each
      medicine, therapeutic groupings and indicators proposed to measure aspects
      pursued in the interventions. CONCLUSIONS: Through the application of the DDD
      unit of measurement, broad data bases on medicine consumption can be exploited,
      and simplified intuitive information about the use of medicines can be obtained.
      The results of the variations in the indicators linked to the interventions show
      the efficacy of the interventions.

PMID- 9264655
TI  - [Mortality due to suicide in Spain: associated socioeconomic and environmental
      factors].
AB  - OBJECTIVE: Describe the cumulative incidence of suicide mortality and self
      inflicted injuries in Spain during the period 1987-1991 and identify associated
      socioeconomic and meteorological factors. DESIGN: Ecological study. SITE: Fifty
      Spanish provinces excluding Ceuta and Melilla. PATIENTS: Spanish population
      during the study period. MAIN MEASUREMENTS AND RESULTS: For each province, the
      cumulative incidence of mortality from suicide and self-inflicted injuries were
      calculated by gender and age groups. The associations between suicide mortality
      and 31 socioeconomical and meteorological variables were evaluated using multiple
      linear regression. The incidence of suicide deaths was stable during the study
      period. The most important negative associations identified were with variables
      indicating economical development and the positive associations with the variable
      measuring specific general mortality. No significant differences between genders
      were found. For both genders, the model with the highest coefficient of
      determination corresponded to the group of adults aged. CONCLUSIONS: In Spain,
      social and economical factors are associated with the frequency of deaths from
      suicide and self-inflicted injuries in both genders and specially in the adult
      age.

PMID- 9264656
TI  - [Coordination of general and specialized medicine. Evaluation in the Burgos
      area].
AB  - OBJECTIVE: To evaluate the coordination between General and Specialist Medicine,
      its development and the causes of breakdowns. DESIGN: Descriptive at two periods.
      SETTING: Burgos Health Area. PARTICIPANTS: All the consultation request reaching
      Specialist Care (SC) in January 1993 and January 1995 from all the Primary Care
      Centres running the Mostrador programme (23); random sample of these requests in
      order to evaluate the proportion of return six months after the requests and to
      study the data found in the interconsultation notes (ICN) returned to Primary
      Care (PC). MAIN RESULTS: The percentage of requests without and appointment being
      made was similar. 1.21% (1993) and 1.30% (1995); the most common cause was
      error/lack of data. The percentage of ICN returned to PC 6 months after the
      requests was also similar: 24.10% (1993) and 22.03% (1995). The most frequent
      reason for the failure in the circuit was that the specialist "retained" the
      ICNs. CONCLUSIONS: General Medical and Specialist coordination was similar in the
      two periods evaluated. It was adequate for the appointment-making process, but
      there were break-downs in communication between doctors using the ICN. The most
      important reasons for these failures were identified.

PMID- 9264657
TI  - [Acute respiratory infections (ARI) in the 0-14 years of age group during the
      winter period].
AB  - OBJECTIVE: Identification of factors associated with suffering Acute Respiratory
      Infections (ARI). DESIGN: A descriptive study using a direct survey. SETTING: "El
      Naranjo" Primary Care team, Area 9 Madrid. PATIENTS: 362 patients between 0 and
      14. MEASUREMENTS AND MAIN RESULTS: 362 interviews were carried out, covering
      items connected with personal background, living conditions, situation and
      quality of life and activities, 180 patients attending with clinical symptoms of
      ARI were interviewed, as well as 182 who attended during the same period for
      other reasons. The profile of the patients interviewed was mainly: females
      between 6 and 10, with more history of catarrh than any other pathology, and who
      had taken aspirin to treat symptoms and mainly Penicillin as an aetiological
      treatment. They lived in homes measuring 100 square metres, with three bed-rooms
      which were shared in the main by two people, and had one brother aged between 1
      and 9. CONCLUSION: No protective factors against ARI were found in the group of
      children studied.

PMID- 9264659
TI  - [Evaluation of the record of preventive activities of adolescents in a health
      district].

PMID- 9264660
TI  - [Multicenter studies of primary care: the experience of the EIBAL study].

PMID- 9264658
TI  - [Self care and primary care].

PMID- 9264661
TI  - [Experience in rotation in health centers of 6th year students of School of
      Medicine of Saragossa].

PMID- 9264662
TI  - [Accessibility of diagnostic techniques. A way to improve care? Apropos of 2
      cases of inflammatory bowel disease].

PMID- 9264663
TI  - [Angioedema and taking captopril].

PMID- 9264664
TI  - [Conjugal violence: clinical significance].

PMID- 9264665
TI  - [Students, the university and family medicine].

PMID- 9264666
TI  - [The factors related to the research activities of primary care physicians].
AB  - OBJECTIVE: To find the factors related with the research activities of primary
      care (PC) doctors in Catalonia, especially their motivation and the obstacles to
      research perceived by the doctors themselves. DESIGN: An observational, crossover
      study. SETTING: Primary care doctors in Catalonia. PARTICIPANTS: The number of
      doctors (1,286) was divided into two: a) doctors who had published between 1989
      and 1994 (n = 146), b) doctors who had not published. INTERVENTIONS: A survey
      concerning personal and workplace variables was carried out by post. RESULTS: The
      reply percentage was 49.5% (63.7% among those who had published and 44.85% among
      those who had not). The multivariant analysis showed a significant link between
      publishing and postgraduate residence training (MIR), the fact of working in a
      teaching centre and working in a centre with more than ten doctors. CONCLUSIONS:
      Research is close related to postgraduate residence training (MIR), work in a
      teaching unit and PC centres with over ten doctors. Care load, lack of time and
      difficulty in getting financing were the main obstacles to research given by the
      doctors polled.

PMID- 9264667
TI  - [The epidemiological characteristics of brucellosis in the primary health care
      district of Sierra de Cadiz].
AB  - OBJECTIVES: To find the incidence of brucellosis, and analyse its epidemiological
      characteristics and the evolution of the cases recorded in the Sierra de Cadiz
      Primary Care (PC) Area during 1992. DESIGN: A prospective longitudinal incidence
      analysis, with a nested study of cases and controls. SETTING: Sierra de Cadiz PC
      Area. PATIENTS AND OTHER PARTICIPANTS:  CASES: members of the cohort who
      developed the disease. CONTROLS: sample of members of the cohort free of
      Brucellosis paired for age, gender and town of origin. MEASUREMENTS AND MAIN
      RESULTS: Incidence was 52.39 per 100,000, 66.27 and 38.20 per 100,000 in men and
      women, respectively. Highest incidence was at between 15 and 49 years of age
      (67.70 per 100,000). CASES in the Spring predominated (chi 2 = 16.77, gl = 3, p <
      0.05). The most affected professional group was farmers/herders (RR = 4.59, CI
      95%, 2.05-10.26). CONCLUSIONS: The Sierra de Cadiz is an area with endemic
      brucellosis, especially in the districts of Olvera and Ubrique. Its work-related
      character is clear, in spite of the digestive tract being the main transmission
      path.

PMID- 9264668
TI  - [An analysis of the referrals of primary care physicians to a hospital
      hypertension unit].
AB  - OBJECTIVES: To describe the referral of hypertense patients from primary care to
      a hospital arterial hypertension unit, the quality of the information sent and
      the profile of the referred patients. DESIGN: A descriptive crossover study.
      SETTING: The Hospital Clinico of San Carlos in Madrid. PATIENTS AND OTHER
      PARTICIPANTS: A simple random sample of 368 clinical records belonging to
      patients attended at the unit over the last 3 years. MEASUREMENTS AND MAIN
      RESULTS: 54.6% of patients were referred from primary care. 48.9% of the
      interclinical (IC) notes were high-quality, with 28.7% acceptable. 36.8% of
      referrals were considered incorrect, 30.3% because of false unresponsiveness to
      treatment. Good or acceptable IC notes were associated with 94.1% of correct
      referrals and only 65.4% of incorrect referrals. CONCLUSIONS: A high proportion
      of referrals which were incorrect by the consensus criteria were detected and
      were caused by inadequate or insufficient medical treatment. There was a
      statistically significant relationship found between correct referrals and the
      quality of information sent in the IC note.

PMID- 9264670
TI  - [Adverse drug reactions and a program of voluntary notification: an opinion
      survey of primary care physicians].
AB  - OBJECTIVES: To discover the view of primary care doctors on aspects of the safety
      of medicines, their knowledge of the programme of automatic notification of
      negative side-effects of medicines (NSEM), their opinion of the programme and
      factors affecting low notification. DESIGN: A survey of views. SETTING: Madrid's
      Health Area 1. PARTICIPANTS: General practitioners and paediatricians (n = 417).
      MEASUREMENTS AND RESULTS: 281 doctors (67.4%) replied. 88.4% (48 + 40.4%) said
      they included questions on possible side-effects in the case history interview
      (always or almost always). 58.2% suspected at least one negative side-effect each
      month. CONCLUSIONS: Doctors are very interested in detecting and identifying the
      NSEM of their patients, and therefore believe that a centralised system to record
      NSEM should be set up.

PMID- 9264669
TI  - [The evaluation of an incentive system for the primary care professionals of
      Mallorca].
AB  - OBJECTIVE: To describe the assessment made by Mallorca's primary care
      professionals of the economic incentives system set up in 1994 and find their
      opinions of financial incentives and other motivating mechanisms. DESIGN: A
      descriptive, crossover study. SETTING: Primary care in Mallorca (INSALUD of the
      Balearics). PARTICIPANTS: All the health professionals and ancillary workers
      (554) of Mallorca's 24 Health Centres. MEASUREMENTS AND MAIN RESULTS: A self
      filled questionnaire was used as a measuring instrument. There was a 74% reply
      rate. Their assessment of the incentives system used was that the distribution of
      the incentives was unjust and a cause of tension. However, expectations as to the
      amount received had been met to a reasonable extent. Self-management was a
      stronger motivating force than incentives (48.4% vs 13.6%). CONCLUSIONS: The
      incentives system used displayed certain faults (in distribution and the work
      atmosphere generated). However, decentralization was shown to be a powerful
      motivating force. Monitoring professionals' expectations and the fulfillment of
      them should be integrated into management habits.

PMID- 9264671
TI  - [The prediction of the degree of metabolic control by minimal technical norms in
      a diabetes program].
AB  - OBJECTIVE: To assess whether scores on the minimum technical norms (MTN) of the
      diabetes mellitus programme are of use in determining the level of metabolic
      control achieved. DESIGN: A retrospective study. SETTING: Two teaching health
      centres in the city of Santander. PATIENTS AND OTHER PARTICIPANTS: 204 patients,
      the total chosen by the Santander area management for the 1994 annual evaluation
      of the Diabetes programme. MEASUREMENTS AND RESULTS: The values reached by the
      variables of the MTN were measured. For a control criterion we took the value of
      glycosylated haemoglobin HbA1C or over. 52% of patients fulfilled the criteria of
      good control, 20% acceptable and 28% bad. CONCLUSIONS: Scoring on the MTN has
      little value in predicting lower values of HbA1C and is no use in assessing the
      level of metabolic control achieved by the Diabetes programme. The evaluation of
      the programme should include results indicators.

PMID- 9264672
TI  - [The prevalence and characteristics of breast feeding in the rural environment].
AB  - OBJECTIVES: To find the characteristics of breast-feeding (BF) in our community
      in terms of the number of women who started it, its prevalence, average duration,
      reasons for stopping, and related social and family factors. DESIGN: A
      descriptive, longitudinal study. SETTING: Health District of Piedrabuena, Ciudad
      Real. PARTICIPANTS: All the 170 children born between January 1993 and March
      1995, excluding newly-born low-weight babies or ill ones. MEASUREMENTS AND MAIN
      RESULTS: On the first visit (15 days after birth) the mother was asked what kind
      of feeding she gave and, if relevant, the reason for giving up breast-feeding.
      Age of the mother, whether she smoked, number of children, educational level and
      job were obtained from medical records or direct questions. New feeding controls
      were made at 1, 2, 3, 5, 7 and 9 months of life. Giving up BF meant the end of
      the period of study. CONCLUSIONS: 1) Rate for starting BF and its average
      duration was below the recommended, but above the rates found in similar studies.
      2) There was a tendency to give up BF after three months. 3) Hypogalactia was the
      main reason for not starting and giving up BF. 4) The negative influence of
      tobacco on the duration of the BF.

PMID- 9264673
TI  - [Health information systems: the network of epidemiological surveillance and
      primary care. The current situation].

PMID- 9264674
TI  - [Cancer mortality in Huelva: comments].

PMID- 9264675
TI  - [Unemployment and mental health].

PMID- 9264676
TI  - [Scientific production in primary care by autonomous communities].

PMID- 9264677
TI  - [Meningococcal serogroup C meningitis: a situation for alert or alarm? The Group
      of Transmissible Diseases of the PAPPS. Program of Prevention and Health
      Promotion in Primary Care].

PMID- 9264678
TI  - [Maternity in adolescents in the districts and neighborhoods of Barcelona: its
      association with the socioeconomic level and the prevalence of low weight at
      birth. The Working Group of Maternal-Child Health of the Municipal Institute of
      Health of Barcelona].
AB  - OBJECTIVE: To describe the distribution of birth rates and low birth weight among
      teenagers from the health districts and neighbourhoods of Barcelona and their
      association with social and economic level. DESIGN: Environmental study. SETTING:
      City of Barcelona. METHODS: The birth rates for under-20 year olds resident in
      Barcelona for the periods 1980-1982, 1987-1992 and 1990-1992 were calculated. The
      index of family economic capacity (IFEC) was used as a social and economic
      indicator. The coefficient of Spearman was used as a correlative measurement.
      MEASUREMENTS AND MAIN RESULTS: Between the periods 1980-1982 and 1990-1992, a 65%
      drop in the adolescent birth rate was observed. The correlation of birth rates
      with the IFEC for the district fell from -0.91 to -0.69 in the same period.
      CONCLUSIONS: Adolescent birth rates have very uneven geographical distribution,
      which correlates with the distribution of income. The percentage of low weight at
      birth is higher in the poorest districts, but the association with IFEC is much
      weaker.

PMID- 9264679
TI  - [Contraception in adolescents included in a family planning program].
AB  - OBJECTIVE: To describe the motives of consultation, kinds of contraceptive
      methods and side-effects of oral contraceptives (OCs) in adolescent users of a
      family planning program. DESIGN: Family planning program at the District Primary
      Care Unit, Cadiz, Spain. PATIENTS: 283 adolescent females who requested
      attendance in a family planning program from January 1993 until January 1994.
      MEASUREMENTS AND MAIN RESULTS: A medical history of every adolescent was carried
      out and every patient was examined. Those who were recommended the use of OCs
      passed through 3 controls: at the beginning, after the 6th month and after 1
      year. These controls consisted in recording sexual risk behaviours as well as
      several analytic tests. RESULTS: Most adolescents requested the prescription of
      contraceptive methods (81.7% of the most prescribed and demanded methods were
      OCs). We found no serious side-effects after 1 year, so we can conclude that OCs
      are an usefull contraceptive choice for sexually active adolescents because of
      its security, acceptance and easy use.

PMID- 9264680
TI  - [An analysis of the information in the Medicom International Vade Mecum with
      respect to drugs with vitamin A].
AB  - OBJECTIVE: Determination of whether rational drug use is facilitated by the
      quality of the information provided by the Medicom International Vademecum on
      drugs containing vitamin A as active component. DESIGN: Descriptive study.
      SETTING: Primary, specialized and hospital health care within the national
      context. SUBJECTS: Total drugs containing vitamin A, included in the 1995 Medicom
      International Vademecum. MEASUREMENTS: Systematic analysis of the information
      contained in the technical note on drugs containing vitamin A included in the
      Medicom International Vademecum, with respect to several parameters. RESULTS: The
      Medicom International Vademecum lists a total of 37 drugs containing vitamin A
      (35 in combination). A total of 112 different indications are given; 74 are not
      accepted in the literature, and 29 are related to the active components present
      in combination with vitamin A. CONCLUSIONS: The analysis of the technical
      information provided by the Medicom International Vademecum on medications
      containing vitamin A reveals major deficiencies in the parameters investigated.

PMID- 9264681
TI  - [The validity of 6 indirect methods for assessing compliance with pharmacological
      treatment in dyslipidemias].
AB  - OBJECTIVE: To validate six indirect methods of identifying patients who do not
      comply with their treatment with hypolipaemiant drugs. DESIGN: A prospective
      study. SETTING: Primary care centres in the province of Alicante. PATIENTS: 107
      lipaemic patients, on the lists of 5 General Medical practices and on drugs
      treatment. MEASUREMENTS AND MAIN RESULTS: The most accurate way to assess
      compliance was the surprise counting of pills in patients' homes. Patients who
      had between 80 and 110% compliance were defined as compliant. The six indirect
      methods validated were: Communication of self-compliance (CS), Attendance at
      appointments (AA), Doctor's judgment (DJ), Information about the illness (II),
      the Morisky-Green test (MG) and the grade of control (GC). AA, DJ and CS were the
      methods with highest specificity (91.2%-89.5%). GC and II were the most sensitive
      (88%-82%). GC obtained the greatest negative predictive value (77.7%), and DJ the
      greatest positive predictive value (73.6%). The concordance index (kappa) ranged
      from 0.23 for GC and -0.002 for II. CONCLUSIONS: GC, DJ and CS are the methods
      with the best validity indicators and concordance. They could, therefore, be used
      together in clinical practice to identify patients not complying with their
      hypolipemiant treatment.

PMID- 9264682
TI  - [Episodes of disease taken care of in general practice/family medicine according
      to demographic context (I): morbidity].
AB  - OBJECTIVES: To identify the population seen at general/family medical practices
      and quantity the episodes of illnesses attended, in function of the demographic
      context. DESIGN: An observational, prospective study based on a year-long record.
      SETTING: 43 practices spread over 10 autonomous communities. INTERVENTIONS:
      Identification, sex and date of birth of each patient attended, the type of
      episode, health problem and date of their first consultation, were all recorded.
      Standardisation by the indirect method was used to compare morbidity rates.
      RESULTS: 2.39 episodes per person seen were attended in rural areas, 2.42 in
      urban ones, and 2.45 in mixed areas. The rural context had rates below 15% of the
      standard rate for neoplasias, endocrine diseases, neurological illness and
      additional categories; and over 15% for digestive tract diseases, traumas and
      side-effects. The urban context had higher rates for neoplasias, endocrine, blood
      and neurological diseases, and additional categories; and lower for respiratory
      system illnesses. In the mixed areas, rates were higher for contagious,
      neurological, respiratory system and congenital diseases. CONCLUSIONS: The
      morbidity attended varies in function of context. Some differences could be due
      to age distribution (younger in the mixed areas) or accidents (greater in rural
      areas). Others could be affected by use or problem-solving criteria varying
      according to the demographic context.

PMID- 9264683
TI  - [Specialized care and primary care in the treatment of asthma: do differences
      exist?].
AB  - OBJECTIVE: To determine whether differences exist in the monitoring, diagnosis
      and treatment of asthmatic patients between family doctors (FD) and pneumology
      specialists (PD). DESIGN: A descriptive crossover study, performed through an
      interview with the patients and a medical exploration. SETTING: Six health
      centres. PATIENTS: 195 asthmatic patients between 14 and 65, chosen by simple
      random sampling from among all those registered by computer in the SICAP.
      MEASUREMENTS AND MAIN RESULTS: Each patient answered a structured interview and
      had a spirometry test. Which doctor usually monitored their illness, social and
      demographic data, morbidity parameters, treatment prescribed and their compliance
      with it, were all determined. 66% of patients were under their FD. No differences
      were found in the clinical characteristics of patients treated by their FD
      against those treated by their PD. CONCLUSIONS: Most adult asthmatics are under
      the care of FDs; however, these appear to under-treat to a considerable degree,
      especially respecting the use of inhaled corticosteroids. It must be emphasised
      strongly that Asthma is an inflammatory disease; and FDs must become better
      informed of the directives of the international consensus on asthma.

PMID- 9264684
TI  - [Care for the terminal cancer patient in a primary care district].
AB  - OBJECTIVE: To analyse medical care for terminal cancer patients (TCP) in a health
      district. DESIGN: A descriptive, crossover study. SETTING: primary care in an
      urban environment. PATIENTS: 227 patients who died of cancer between January 1994
      and June 1995 and who came under the nine primary care teams (PCT) studied.
      MEASUREMENTS AND MAIN RESULTS: Information bases: mortality records and clinical
      histories from the PCT. VARIABLES STUDIED: age, sex, type of tumour, date of
      diagnosis of terminal illness, whether treated or not with morphine and (if so)
      the doses, place of death and the care activity engendered. Univariant analysis
      with standard means and deviations for the quantitative variables, frequencies
      for the qualitative ones and the Chi squared test for comparison. 64% were male.
      Most common neoplasias were, in order: lung, colon and stomach. 78 patients (49%)
      received morphine treatment, datum related to age. Average morphine dose was 80
      mg in 24 hours. CONCLUSIONS: Patient treatment was inadequate because morphine,
      the lodestone of terminal cancer care, was insufficiently used. In contradiction
      with WHO recommendations, most patients died in hospital. Specific training
      programmes should be created for PC professionals with the aim of improving their
      handling of terminal cancer patients.

PMID- 9264685
TI  - [The quality of antibacterial prescription in a primary care district. Its
      evolution in 1994-1995].
AB  - OBJECTIVES: To analyse the profile and quality of antibacterials (ABs)
      prescription in a primary care (PC) district during 1994 and 1995. DESIGN: A
      longitudinal, descriptive and retrospective study. SETTING: PC doctors from the
      PC district Bahia de Cadiz (Cadiz). MEASUREMENTS AND MAIN RESULTS: The
      prescriptions for ABs belonging to the following groups were studied: JO1
      (systemic antibiotics), JO3 (systemic chemotherapy drugs), GO4A (antiseptics and
      drugs for urinary infection) and RO5C1 (expectorants, with mucolytic drugs
      included with anti-infection ones). The unit of measurement was the daily defined
      dose (DDD). DDD per 1,000 inhabitants per day (DID) and the DDD percentage of
      each AB versus the total were used as quantitative indicators. The qualitative
      indicators were: origins of use of ABs in PC and %DDD of non-justified
      associations (NJA) (RO5C1 group). CONCLUSIONS: The prescription profile of ABs in
      the area is similar to, and somewhat more favorable than, that described in the
      literature for similar areas. In the reconverted network there was a more
      rational prescription than in the non-reconverted network for the two years of
      the study. In both types of network a light improvement in the indicators studied
      was observed from 1994 to 1995.

PMID- 9264686
TI  - [Reform and neoliberalism].

PMID- 9264687
TI  - [Towards a reform that respects the principles of primary care].

PMID- 9264688
TI  - [Health promotion facing the crisis in modern medicine].

PMID- 9264690
TI  - [Mental disorders in primary health care].

PMID- 9264689
TI  - [Bacteriology and resistances in outpatient urinary infections].

PMID- 9264691
TI  - [Nitric oxide--a novel physiological messenger: possible role in central nervous
      system pathology].

PMID- 9264692
TI  - [The effect of inhibition of subretrofascial region on the central inspiratory
      activity of the respiratory center and reaction of respiration to hypercapnia].

PMID- 9264693
TI  - [The effect of neurotensin and adrenaline on sinus arrhythmia during firing
      stimulation of the vagus nerve].

PMID- 9264695
TI  - [Functional characteristics of hypothalamic and cortical neurons in various
      motivational and emotional states of animals].

PMID- 9264694
TI  - [Opioid peptides modulate secretion of major determinants of bile flow].

PMID- 9264696
TI  - [Pathophysiological effects of combined exposure to emotional stress and
      cyclophosphamide].

PMID- 9264697
TI  - [The role of heart autonomic nerves in the mechanism of antiarrhythmic effect of
      beta-endorphin during experimental myocardial ischemia].

PMID- 9264698
TI  - [Prevention of ischemic impairment of contractile function of isolated heart
      using short-term periods of total ischemia].

PMID- 9264699
TI  - [Effect of Rodiola rosacea on the resistance of isolated heart from stressed-out
      rats to ischemic and reperfusion injury].

PMID- 9264700
TI  - [Hibernating peptides, neokyotorphin and kyotorphin, have positive effect on
      cardio-pulmonary and cerebral resuscitation in rats after a 12-min heart arrest].

PMID- 9264701
TI  - [Mechanisms of regulation of activity of lysosomal thiol proteinases in the
      thyroid gland: effects of protein synthesis inhibitors].

PMID- 9264702
TI  - [Effect of irradiation on the vitamin status and spermatogenesis in rats].

PMID- 9264703
TI  - [Effect of thyroid hormones on neurosecretory cells of rat supraoptic and
      paraventricular hypothalamic nuclei in vitro].

PMID- 9264704
TI  - [The role of Na+/K+-ATPase in the presynaptic aftereffect of exogenous
      acetylcholine in rat diaphragm].

PMID- 9264707
TI  - [Relationship between changes in factors of nonspecific resistance during
      traumatic and burn shock].

PMID- 9264705
TI  - [Effect of Ca2+,Mg2+-dependent endonuclease activation on the proliferative
      response of human peripheral blood lymphocytes].

PMID- 9264706
TI  - [The role of prostaglandin E2 in the neurohumoral regulation of cardiovascular
      system].

PMID- 9264709
TI  - [Autostimulation of prolactin receptors in the guinea pig adrenal cortex].

PMID- 9264708
TI  - [Effect of sufan, lidocaine and their combination on the course of early
      occlusive and reperfusion arrhythmias in cats].

PMID- 9264710
TI  - [Optimization of a method of infusion of reverse agonists of GABA-receptor
      complex in analysis of rapidly reversible effects of tranquilizers and ethanol].

PMID- 9264711
TI  - [Mechanisms of hemostimulating effect of glyciram].

PMID- 9264712
TI  - [Experimental study of a possibility of serodiagnosis of pseudotuberculosis in
      man using immunoblotting].

PMID- 9264713
TI  - ["Graft versus leukemia" during mixed chimeric hematopoiesis].

PMID- 9264715
TI  - [Bridges and multipolar mitoses in populations of rat rhabdomyosarcoma RA-23
      cells].

PMID- 9264714
TI  - [Ca-19-9, carcinoembryonic antigen, and alpha-fetoprotein in the serum of
      nononcological patients and their clinical significance].

PMID- 9264716
TI  - [Cytotoxic activity of murine thrombocytes].

PMID- 9264717
TI  - [Dynamics of parameters of immune status in oncological patients treated with
      preparations of fetal origin].

PMID- 9264718
TI  - [Hemodynamic reactions in acute period of massive embolism of pulmonary
      arteries].

PMID- 9264719
TI  - [Effect of aseptic inflammation on structural organization of trophoblast and
      proliferative activity of embryonal liver and lung cells].

PMID- 9264720
TI  - [Morpho-functional changes in the thymus and lymph nodes during different methods
      of irradiation with helium-neon laser].

PMID- 9264721
TI  - [Morpho-functional changes in renal blood vessels during experimental aortic
      coarctation and after its surgical treatment].

PMID- 9264722
TI  - [Quantitative evaluation of biological activity of toxic agents (unicellular
      model)].

PMID- 9264723
TI  - [Organization of prenatal care and delivery].

PMID- 9264724
TI  - [Experiences with external quality assurance in gynecologic surgery].
AB  - A project, 'Quality Management in Gynecological Surgery', was developed as an
      external means of quality management in gynecological surgery and tested in 44
      clinics in 1994. The external comparison of clinics generally demonstrated the
      high quality of the services, but certain aspects of these services exhibited an
      extremely high variability, for instance as far as thrombosis prevention and the
      choice of the routes of access for defined interventions are concerned. The
      positive effects of the project were that the clinics used the comparative data
      provided by the project as a basis to modify the management processes and thus
      improved the quality of their services. On the other hand, the external
      comparisons uncovered the need for guidelines for the management of patients. It
      will now be the responsibility of the gynecological societies to establish such
      guidelines and communicate them to their members via the appropriate channels.

PMID- 9264725
TI  - [Fetal ultrasound biometry and amniotic fluid insulin concentration in pregnant
      diabetic patients].
AB  - OBJECTIVE: The aim of the study was to prove the sensitivity of sonographic
      measurements for the presence of a fetal hyperinsulinism. METHODS: In a
      longitudinal examination of 102 insulin-dependent diabetics we show the
      correlation between the amniotic fluid insulin level and the biparietal diameter,
      abdominal diameter and femur length in the third trimester. The control of the
      maternal metabolic state was done by measuring the glycosylated hemoglobin and
      fructosamine at the time of the amniocentesis. RESULTS: The sensitivity,
      specificity, positive and negative predictive value of sonographic measurements >
      75th percentile in fetal hyperinsulinism was for the biparietal diameter 21, 96,
      81 and 62%, for the abdominal diameter 48, 82, 69 und 66%, and for the femur
      length 22, 90, 67 and 57%. The maternal glycoproteins did not show any
      correlation with the amniotic fluid insulin level. CONCLUSIONS: The results
      demonstrate that fetal hyperinsulinism cannot be proved by fetal biometry or
      evaluation of the maternal metabolic state.

PMID- 9264726
TI  - [Effect of the mode of delivery on the newborn infant with gastroschisis. With
      data from the Styrian Malformation Register].
AB  - OBJECTIVE: Our purpose was to investigate the influence of the mode of delivery
      on the outcome of children with gastroschisis. METHODS: 38 children were born and
      treated at the University Hospital of Graz between 1977 and 1995. The perinatal
      and surgical data were analyzed retrospectively. Furthermore, we compared the
      prevalence of gastroschisis in Styria to international data. RESULTS: The mode of
      delivery did not influence the fetal outcome. The higher rate of acidosis and
      shorter interval from rupture of the membranes to delivery in cases of cesarean
      section may be attributable to the obstetric decision for an operative delivery.
      The prevalence of gastroschisis is high as compared to European data.
      CONCLUSIONS: Our data and the majority of publications do not show a benefit of
      cesarean section for children with gastroschisis. A randomized prospective trial
      is still lacking to end controversies.

PMID- 9264727
TI  - [Tainted femininity--traces of traditional menstruation myths in product
      advertising of feminine hygiene products].
AB  - OBJECTIVE: Does the portrayal of menstruation in menstrual product advertisements
      reflect cultural myths about menstruation? METHODS: We analyse the reception of
      menstruation in contemporary and historical menstruation product advertisements.
      RESULTS: In menstrual product advertisements, menstruation is depicted as an
      unclean attribute, discrediting an ideal femininity and creating the need to
      conceal it. CONCLUSION: This tendency to taboo menstruation in menstrual product
      advertising contributes--by conveying a negative definition of femaleness--to a
      negative self-perception, particularly in young women.

PMID- 9264728
TI  - [Second look laparoscopy after fallopian tube perforation with the tubal
      endoscope].
AB  - In recent years, falloposcopic, visualization of the tubal lumen has become a
      topic of great interest. The development of a linear everting catheter system
      (Imagyn Medical Inc., Laguna Niguel, Calif., USA) allows cannulation of the
      fallopian tubes without exerting shear forces upon the tubal epithelium. We
      report the findings of a second-look laparoscopy after accidental tubal
      perforation at falloposcopy. Second-look laparoscopy was performed in a patient 6
      months after tubal perforation with the falloposcope and no adhesions or signs of
      inflammation could be detected. On chromopertubation, no tubal fistula was found
      to be present. Two months after treatment, the patient got pregnant
      spontaneously. Pregnancy and delivery were without any complications. We conclude
      that technique of falloposcopy provides a safe access to the endotubal lumen.
      Even a perforation created by the microendoscope does not appear to be associated
      with any long-term complications.

PMID- 9264729
TI  - [Spontaneous pregnancy after ligation of the uterine artery].
AB  - In this case report, the functional anastomoses of the uterine arteries are
      demonstrated. In our opinion, the selective ligation of one or both uterine
      arteries is the method of choice for treating severe gynaecological or
      obstetrical bleeding complications. Successful haemostasis and preservation of
      the uterus can be achieved permitting future spontaneous pregnancies.

PMID- 9264730
TI  - [Does it make sense to carry out a Vecchietti intervention pelviscopically?].
AB  - The Mayer-Rokitansky-Kuster syndrome is the most frequent cause of vaginal
      aplasia. There are several operations that can correct this malformation; the
      most important is that of Vecchietti. The rapid development of the laparoscopic
      know-how in the last years enables a pelviscopic approach of the laparotomic part
      of the Vecchietti operation. The question remains whether there are real
      advantages or whether the choice between laparotomy and laparoscopy should depend
      exclusively on the personal experience of the surgeon.

PMID- 9264731
TI  - [Experience with hysteroplasty. Indications, technical references, postoperative
      and long-term outcome].
AB  - The authors report their experience with hysteroplasty carried out at the
      gynecological clinic of the University of Verona between 1974 and 1981 and the 10
      year follow-up of these patients. Of 46 operated patients, 4 had uterus septus,
      38 uterus bicornis (31 bicornis unicollis and 7 bicornis bicollis) and 4 uterus
      didelphys. The Strassman intervention was used in 32 cases, the Bret-Palmer
      intervention in 13 and Jones intervention in 1. The results were very good in 16
      cases, satisfactory in 22 and moderate in 8; no negative result has been seen. 38
      patients had later a baby. In 4 cases, the uterine malformation was associated
      with sterility, but this was caused by endometriosis or by pelvic inflammatory
      disease; therefore, the malformation is not the primary indication for surgery.
      The best results were achieved in cases of uterus septus or uterus bicornis.

PMID- 9264732
TI  - [A preoperative diagnostic concept for determining the extent of laparoscopic
      surgery of the adnexa].
AB  - The operative laparoscopic therapy of pre- and postmenopausal adnexal tumors has
      become more and more important in routine gynecological surgery. Careful
      evaluation of malignancy criteria by preoperative diagnostics decides whether
      endosurgical treatment or laparotomy should be performed. Preoperative diagnostic
      measurements must secure a safe and efficient endosurgery without any negative
      financial impact due to unnecessary explorations. The proposed diagnostic concept
      offers maximal security with minimal investigations.

PMID- 9264733
TI  - [Leishmania (Viannia) braziliensis Vianna, 1911 in French Guiana. Clinical,
      therapeutic and epidemiological considerations in the ninth human diagnosed
      case].
AB  - The authors report the ninth case of cutaneous Leishmaniasis without mucosal
      involvement due to Leishmania (Viannia) braziliensis (isoenzymatic profile
      related to zymodeme MON-44) diagnosed in a legionnaire who recently arrived in
      French Guiana. The skin lesion as a single ulcerated nodule of the dorsum of the
      left ringfinger was cured after two courses of four intramuscular injections of
      pentamidine isothionate (total posology of pentamidine-base: 16.6 mg/kg). The
      transmission occurred during nocturnal trekking in forest and swamps just behind
      the coastal belt at Degrad Saramaka (7 km South of Kourou). In French Guiana, the
      good level of medical care and the early treatment of the majority of the cases
      of Leishmaniasis may explain the rarity of mucosal lesions. Since the clinical
      aspect of the lesion is not sufficient to prejudge the identity of the causative
      species, it is necessary to perform cultivation of Leishmania for iso-enzymatic
      identification. The adaptation of pentamidine doses and long term follow up of
      patients infected by L. (V.) braziliensis could be defined more precisely.

PMID- 9264734
TI  - [Ophthalmologic complications due to human immunodeficiency virus infection at
      Bamako (Mali)].
AB  - AIDS ocular complications have been researched in 70 hospitalised patients in the
      two main hospitals of Bamako (Mali) during one year (1992-1993). Men were
      predominant (sex ratio 1.6). HIV1 infections (67%) were most frequent than HIV1 +
      HIV2 (21.4%) or HIV2 infections (11.4%). Most of the patients were on the WHO's
      clinical stage III; 34% of them had ocular complications, quite often non
      infectious: cotonous nodules (10%), vascularitis (5.7%) and retineous
      haemorrhages (4.3%). Ocular opportunistic infections were rare: only one case of
      toxoplasmic chorio-retinitis was reported. Ocular complications were observed
      with all types of HIV. Vascular abnormalities were observed in the stage II or IV
      of AIDS and seemed, in Bamako, as a serious sign during the AIDS course.

PMID- 9264735
TI  - [Clinical exercise: recalcitrant diarrhea in the main hospital of Dakar ].
AB  - It's the case of a Senegalese man who presents a chronic rebel diarrhea with
      alteration of the general condition and a malabsorption. The aetiologic
      management has been very difficult to achieve after we have eliminated the
      infectious and parasitological causes. The clinical and epidemiological context
      with the histopathological arguments allowed us to establish the diagnosis of
      intestinal tuberculosis.

PMID- 9264736
TI  - [Use of antibiotics in pediatric surgery at the University Hospital Center at
      Yopougon, Abidjan (Ivory Coast)].
AB  - Considering 901 files of in-patients (68% of boys and 32% of girls, mean of ages:
      2 days to 16 years) and prescriptions at the hospital of Yopougon during a period
      of two years (1991-1992), the authors have made a retrospective and critical
      study of the use of antibiotics in this department. Antibiotics, either demanded
      by strong presumption of infection, either indicated as a prophylaxis, have been
      administered to 54% of the patients. When this antibiotic therapy has been
      curative (56% of the cases of first intention), it was considered correct in 97%
      of the cases. On the other hand, it was ill-done when it was a matter of
      antibioprophylaxis. An antibiotherapy of second intention has been prescribed
      when antibiotherapy of first intention had failed and also when the antibiotic
      reserve of the hospital was over. The average number of antibiotics given to a
      patient was 2.12, frequently associating aminoside and penicillin. The total cost
      of antibiotics was 78% of the whole drugs used to cure these patients and among
      them, the biggest cost was for cephalosporines of third generation.

PMID- 9264738
TI  - [Hygiene and microbiologic quality of ice creams produced in Cameroon. A public
      health problem].
AB  - Three hundred samples of ice cream produced in two main towns in Cameroon (Douala
      and Yaounde) are evaluated for their hygienic quality. The microbiologic
      examinations show that many of them are contaminated with bacteria of faecal
      origin, pathogenic Staphylococcus and Salmonella respectively in 71.3, 49.6 and
      5% of the products examinations in the study. The use of non potable water and
      the disrespect of the hygienic rules during the production are the main causes of
      contamination. Recommendations are made to preserve the public health in the
      developing country.

PMID- 9264737
TI  - [Serologic screening of certain zoonoses in the abattoir personnel in Djibouti].
AB  - A sero-prevalence survey was carried out on 108 workers of Djibouti slaughter
      house in order to search out the carriers of agents of zoonotic diseases. The
      sera revealed prevalences of 6.5% for brucellosis, 0.9% for chlamydiosis and
      42.6% for toxoplasmosis whereas no positive reactions were detected for Rift
      valley fever, Crimean Congo hemorrhagic fever, hydatidosis, and toxocarosis.
      These data are compared with results obtained from cattle and small ruminants
      slaughtered in Djibouti.

PMID- 9264739
TI  - [Argas and arbovirus update].
AB  - At the opportunity of the recent discovery of a new Phlebovirus, Tunis virus, the
      authors discuss the importance of the genus Argas as for its potential role in
      the transmission of arboviruses: twelve species of Argas are known to carry about
      twenty viruses. The wide distribution of Argas reflexes hermanni prompt us to
      explain its position in the Argas reflexes "complex" group: this species seems to
      be more liable to infection by viruses. Some ecological and entomological data
      are added to facilitate its typing. The Tunisian specimens recollected are
      remarkable by the lack of seta n degree 5 on basis capituli.

PMID- 9264740
TI  - [In vivo drug sensitivity of Plasmodium falciparum in the Tabou region of Ivory
      Coast].
AB  - Malaria caused by Plasmodium falciparum is one of the major health problems in
      West-Africa, mainly affecting young children. This situation is further
      complicated by the emergence and rapid progression of resistance to chloroquine,
      the recommended first line treatment. In order to document the level of
      resistance of P. falciparum to chloroquine, pyrimethamine/sulfadoxine (Fansidar)
      and quinine, we performed a survey in Tabou district, Core d'Ivoire, from June to
      August 1995. This area has been hosting some 100,000 Liberian refugees since
      September 1994. Children aged 1 to 15 years old attending the dispensary with a
      complain of fever or suspected malaria, were included into the study, diagnosed
      and followed for 7 days according to the WHO Standard Field (in vivo) Tests.
      Overall proportion of P. falciparum resistant to chloroquine reached 45.1% and
      was made of 34.3% type II and 10.8% type III resistance. Being less than 5 years
      of age and having received a lower dose of drug were 2 factors associated with
      the risk of resistance to chloroquine. Levels of R II resistance to
      pyrimethamine/sulfadoxine and quinine (3-day treatment) were respectively 5.4%
      and 4.2%. No R III resistance was found in neither pyrimethaminelsulfadoxine or
      quinine treatment groups. These results challenge the current chloroquine-based
      first line malaria treatment in Core d'Ivoire. Alternative based on
      pyrimethamine/sulfadoxine could be considered, especially in high risk
      populations during transient situation (refugees). However, elaborating new
      treatment policy must take into consideration cost, side-effects, compliance and
      acceptability. Further studies are needed to evaluate the cost-benefit of
      alternative strategies.

PMID- 9264741
TI  - [Human African trypanosomiasis in children. A pediatrics service experience in
      Libreville, Gabon].
AB  - During a period of six years (1/1/89-12/31/94), seven children with
      trypanosomiasis were admitted to the Department of Pediatrics of Owendo Pediatric
      Hospital-Libreville, Gabon. They were 5 boys and 2 girls, aged 4-17 years, five
      of them under 15 years. The main reasons of hospitalization were somnolence (4
      cases), psychical disorders (5 cases), neurological disorders (4 cases), asthenia
      (3 cases), loss of weight (3 cases) and fever (3 cases). Increased sedimentation
      rate (5 cases) and hypergammaglobulinemia (6 cases) were the most important
      biological disturbances. Serodiagnosis (CATT, indirect immunofluorescence test)
      was positive in all cases. The parasite was detected in blood seven times, and
      four times in cerebrospinal fluid (CSF). According to CSF status, six children
      have been classified in second stage of the disease. Six patients were treated by
      melarsoprol, and one by eflornithine. Tolerance and response to treatment were
      good in six cases. Three children presented sequels when leaving hospital. No
      patient was seen again after the study.

PMID- 9264742
TI  - [Toxoplasmosis in Iran. Results of a seroepidemiological study].
AB  - A toxoplasmosis seroepidemiological survey was effected with 13,018 sera
      collected by stratified cluster random sampling method from 12 provinces in Iran.
      The samples were studied by indirect immunofluorescent assay (IFA) for the
      presence of Toxoplasma. In this study, 52.6% of the subjects were male and the
      remaining 47.4% were female. Anti-Toxoplasma antibody was detected in a total of
      51.8% of the samples with no significant difference between male and female
      affected subjects. The distribution of the infected samples was also investigated
      in various age groups, the level of infection to Toxoplasma increasing from
      childhood, culminating to 30 years of age and gradually declining from there
      after. Between the various age groups, the 10-19 years old demonstrated a 50%
      increase in relative risk to the infection with high antibody titer. Within the
      provinces under study, the highest relative frequency of Toxoplasma antibody
      titer was indicated in Mazandaran province (20.5%), while the lowest frequency
      was detected in Hormozgan (2.9%). In general, there was a decrease in the number
      of infected samples from humid areas in north to dry provinces in south of Iran.
      In the clinical symptoms study, no significant difference between male and female
      patients was demonstrated. According to the type of clinical manifestation,
      lymphadenopathy and central nervous system symptoms (encephalitis) were
      respectively the most and the least frequent manifestations.

PMID- 9264743
TI  - [Dirofilaria (Nochtiella) repens in the spermatic cord: a new human case in
      Italy].
AB  - A case of human dirofilariasis associated with Dirofilaria (Nochtiella) repens,
      localised in the spermatic duct, is reported in a 52-year-old man from Lugo di
      Romagna (Ravenna province, Northern Italy). It represents the 22nd case of human
      dirofilariasis occurring until now in the same region. According to the relevant
      world literature this appears to be the 2nd case with this rare localisation the
      first one occurring in Italy as well.

PMID- 9264744
TI  - [Malaria attack: a very late relapse due to Plasmodium vivax].
AB  - Plasmodium vivax malaria late-forms rarely exceed two years--the authors reported
      a late-form more than twenty years after a stay in endemic area. This late-form
      occurred in an immunocompromised patient with two terminal-stage neoplasia
      receiving radio, chimio corticotherapy associated with anemia and thrombopenia.
      Repeated-tests allowed the diagnostic.

PMID- 9264745
TI  - [Visceral leishmaniasis in Niger: six new parasitologically confirmed cases].
AB  - From January 1992 to January 1995, six cases of Kala-azar have been observed in
      young soldiers at Niamey, Niger. All the patients had spent some time at Tin
      Galene, in Air mountains, Northern Niger where they had been apparently
      contaminated. One patient was also infected with Salmonella and an other with
      Mycobacterium, but none of the six was positive for HIV. The 6 cases have been
      confirmed by the presence of Leishmania in the sternum bone-marrow. Four patients
      recovered after a treatment with Glucantime; two died because the treatment was
      too late. In Niger, Kala-azar prevalence is probably much higher than estimated
      previously. So far all the cases described or suspected were in the Saharan
      mountains of Air. The strains have not been typed and it is not possible to state
      if it is L. infantum or L. donovani. The vector of the two species Ph. orientalis
      and Ph. alexandri are known to occur in the area.

PMID- 9264746
TI  - [Prevalence of hepatitis C virus infection in the general population of
      Madagascar].
AB  - The achievement of a sera collection representative for the general population >
      or = 1 year in 1994 allowed the assessment of the seroprevalence of Hepatitis C
      virus infection (HCV) in Antananarivo and Toamasina provinces which represent 45%
      of the total population of Madagascar. The overall sero-prevalence was 1.2% among
      the 921 tested sera. The prevalence was not significantly different according to
      sex, but it increased according to the age. The absence of positive children was
      an argument in consideration of the low importance of mother-to-infant
      transmission in the epidemiology of HCV. A significant relationship was observed
      with past history of blood transfusion. This point is a well established idea
      that reminds the interest of the detection of positive individuals for anti-HCV
      antibodies. The seroprevalence observed in our study could be considered as
      moderate. It is close to the values recorded in Europe or in Japan, and much
      lower than those observed in Equatorial Africa.

PMID- 9264747
TI  - [Prognosis of acute intestinal intussusception in infants at the national
      hospital of Niamey (Niger). Eleven cases treated surgically].
AB  - In order to precise the different prognosised factors of the acute intestinal
      invagination of the nursling, authors hereby report results of a prospective
      study lead in the department of general surgery during the period of January 1989
      to August 1990. Eleven nursling have been operated during that period. The study
      of their files showed that the standard clinical triad of the acute intestinal
      invagination theoretically taught in the schools of health sciences, is never
      definitive. The diagnostic lateness and indeed therapeutic and the lack of
      adequate means of pediatric resuscitation constituted the main prognosised
      factors of this affection. The clinical board of the patients is that of an
      advanced occlusion or that of a serious peritonis. The surgical operation often
      consisted in an intestinal resection. The immediate mortality was heavy: 55%. The
      authors hereby stress the necessity of a training-informing-sensitizing of the
      health staff in the primary sanitary facilities and the populations.

PMID- 9264748
TI  - [Selection criteria for the establishment of reference values in tropical zones.
      Application to specific proteins: C-reactive protein, haptoglobin, transferrin in
      gabonese children].
AB  - About 220 children (110 boys and 110 girls) aged 18 months to 10 years, 65.9%
      have been selected from anamnesis, clinical, and biological criteria to produce
      reference values on specific proteins dependent inflammatory, anemia and
      hemolysis (C-reactive protein = CRP; Transferrin = TRF and Haptoglobin: HPT).
      Specimens have been analysed by Nephelometric immuno-chemical method. For the two
      groups, A1 [18 months-5 years] and A2 [5-10 years], the reference values of the
      whole study population are reported: CRP (A1 3.35 +/- 3 mg/l: A2 2.40 +/- 2.30
      g/l, with a significant difference at Student Fisher "t" test p < 0.03); TRF (A1
      4.05 +/- 1.5 g/l; A2 4.50 +/- 1.4 g/l; NS, p > 0.05) HPT (A1 2.55 +/- 2.0 g/l: A2
      1.20 +/- 1.10 g/l; S(r) p < 10(-5)). Furthermore, for TRF, HPT we must consider
      the sex in the results meaning because of significant difference into boys and
      girls.

PMID- 9264749
TI  - [Ivermectin and tropical dermatoses].
AB  - Among tropical dermatoses, the main indications of ivermectine are tropical
      parasitoses such as filariasis and cosmopolitan diseases due to ectoparasites
      such as scabies. The efficacy and tolerance of ivermectine in filariasis
      (onchocerciasis, lymphatic filariasis, loiasis) have been the topic of numerous
      articles and reviews. More recent studies showed that ivermectin was also
      efficient in the therapy of scabies, cutaneous larva migrans and larva currens.

PMID- 9264750
TI  - [In vivo neutralization of physiological cervicovaginal acidity by sperm nitrogen
      bases].
AB  - Cervicovaginal secretions (CVS) from 46 heterosexual African women, attending the
      National Reference Center for Sexually Transmitted Diseases and AIDS of Bangui,
      Central African Republic, were investigated, at inclusion and after vaginal
      douching with water, in order, i) to determine the relationship between
      cervicovaginal pH and the presence of semen components [prostatic acid
      phosphatase (PAP) and prostatic specific antigen (PSA)] in sexually active
      African women; ii) to assess whether vaginal douching performed after sexual
      intercourse could efficiently eliminate semen components and restore
      cervicovaginal acid pH. At inclusion, semen components were found in 41 CVS
      (89%); the mean cervicovaginal pH was 6.12 (range, 3.86 to 8.33); concentrations
      of both PAP and PSA correlated positively and strongly with cervicovaginal pH (p
      < 0.001). After douching, semen components were found in only 31 CVS (67%) (p <
      0.03); vaginal PAP and PSA levels were significantly decreased (p < 0.0001); PAP:
      -21%; PSA: -36%). Frequent persistence of semen in cervicovaginal secretions from
      heterosexually active African women leads to a shift from acidity to neutrality,
      that could favor male-to-female HIV transmission.

PMID- 9264751
TI  - [Effect of hygiene measures, water sanitation and oral rehydration therapy on
      diarrhea in children less than five years old in the south of Ivory Coast].
AB  - The purpose is to assess the impact of compliance with measures of hygiene and
      water supply and oral rehydration on the diarrhoea with under 5 years of age in
      four villages of southern Cote d'Ivoire. The method used is to compare morbidity
      and mortality of children, firstly between two groups of villages without such
      measures, secondly in two villages before and after implementing them. Initially,
      an exhaustive survey has determined the incidence rate of diarrhoea, the
      proportion of deaths resulting from such diarrhoea as well as the mortality rate
      1988. Two similar survey were made in 1990 and 1992. The results show a 50%
      reduction of the incidence rate of diarrhoea and a 85% reduction of the
      proportion of deaths related to diarrhoea in the villages with intervention. The
      mortality rate to diarrhoea was likewise reduced by 85%. These results show the
      importance of the improvement and accessibility to drinkable water and hygiene in
      the prevention of diarrhoea in areas children.

PMID- 9264752
TI  - [Impact of improved sanitary conditions and domestic hygiene on the incidence of
      ascaridiasis and ancylostomiasis in children two to four years old in the rural
      zones of Ivory Coast].
AB  - The purpose of this study is to assess the impact of improvement measures for
      hygiene and water supply, installation of latrines and health education on the
      incidence of ascaridiasis and ankylostomiasis with 2 to 4 years old children in
      some villages of southern Cote d'Ivoire. The method used is the comparison of
      children carrying parasites before and after intervention. Initially in 1988, the
      stools of all children aged from 2 to 4 were collected and examined in order to
      look for the presence of parasites in the stools. Two identical inquiries were
      made in 1990 and 1992. The results show a reduction of the rate of incidence for
      ascaridiasis by 75% and ankylostomiasis by 82%. They demonstrate the importance
      of an appropriate evacuation of excreta, of an education of mothers and of
      domestic hygiene in the process of prevention of children parasitosis.

PMID- 9264753
TI  - [Profile of intestinal helminthiases in school aged children in the city of
      Abidjan].
AB  - Feces of 1001 school children aged from 4 to 15 years were examined as an
      epidemiological investigation. Direct analyses were completed by KATO and RITCHIE
      methods. The outcome was the global prevalence of intestinal helminthiasis in
      school age children in the Abidjan area is 36.5%. Male subjects are more infected
      than females. The most infected group is aged from 12 to 13 years and the less
      infected from 4 to 5 years. The frequent parasite species are Trichuris trichiura
      (23.4%), Ascaris lumbricoides (15.5%), Necator americanus (6.3%), Strongyloides
      stercoralis (1.4%). Hymenolepis nana (1.1%), Schistosoma mansoni (0.8%) and
      Enterobius vermicularis (0.2%).

PMID- 9264754
TI  - [Description of Phlebotomus (Synphlebotomus) saltiae n. sp. (Diptera-Psychodidae)
      of Lebanon].
AB  - Description of the male holotype and of the female of phlebotomus
      (Synphlebotomus) saltiae n. sp.. Morphological comparison with other
      Synphlebotomus previously described. Hypothesis on the origin of the species and
      its vectorial status in leishmaniasis.

PMID- 9264755
TI  - [Prevalence of Helicobacter pylori infection in Tananarive, Madagascar].
AB  - During a 8-month period, Helicobacter pylori infection has been studied in 140
      patients who presented upper gastrointestinal symptoms. Helicobacter pylori was
      searched in antral biopsy specimens using standard bacteriological methods (Gram
      staining, urea-test, culture) and histological staining techniques (hematoxylin
      eosin-saffron, undifferentiated Giemsa). The global prevalence of H. pylori
      infection was 59%. The prevalence rates did not seem to differ with age and sex
      but H. pylori infection was significantly more frequent in patients with an
      active duodenal ulceration (30 of 41) compared with those with a normal endoscopy
      (21 of 47) (p < 0.02).

PMID- 9264756
TI  - Proceedings of the SIMEC 96 4th Brazilian Symposium on Extracellular Matrix.
      Angra dos Reis, RJ, Brazil, September 8-11, 1996.

PMID- 9264757
TI  - [Recommendations of the Polish Pthysiopneumonologic Society for diagnosis and
      treatment of chronic obstructive lung diseases].

PMID- 9264758
TI  - Environmental Pollution and Child Health: Critical Needs and Issues for Central
      and Eastern Europe. Proceedings of an international conference. Sosnowiec,
      Poland, May 8-10, 1996.

PMID- 9264759
TI  - [Decoding facial emotional prototypes].
AB  - This study examined the recognition of the facial prototypes comprised in the
      expressive emotional repertory proposed by Ekman and Friesen (1978a) and by
      Wiggers (1982). The prototypes were shown to 74 decoders who had to rate the
      intensity of the emotion or emotions being portrayed. The results indicated that
      the majority of the prototypes, except those of fear and disgust, clearly
      signaled the predicted emotion. The various prototypes related to the same
      emotion were found to differ in their signal value, some of them being better
      recognized and more specific than others. Some prototypes of fear and disgust
      were found to signal mixed rather than pure emotions. The results also revealed
      that the level of recognition of emotional expression varies according to the
      encoder which suggests that interindividual differences in facial anatomy
      influence the perception of emotion.

PMID- 9264760
TI  - [Prevention of sterility in spinal cord injured men].
AB  - The reproductive function of spinal cord injured males is not the primary concern
      of health professionals responsible for the management of these young adults.
      However, the fertility of these patients is threatened right from the first days
      after trauma, as indicated by abnormalities of the sperm count, reflecting the
      histological alterations observed on testicular biopsy. The factors predisposing
      to asthenoteratospermia, responsible for impaired fertility, are analysed and
      discussed. Urinary tract infection is the leading factor. This acute situation
      must be managed early, by preventing urinary tract infection and by obtaining a
      semen donation as soon as possible, after improvement of the general status.

PMID- 9264761
TI  - [Role of testicular biopsy in the investigation of a carcinoma in situ].
AB  - Carcinoma in situ (CIS) of the testis is recognized to be a precursor of cancer.
      Radiological examinations are not sufficient to improve the diagnosis. So the
      diagnosis is made by testicular biopsy. The indications are controlateral testis
      biopsy in man with testicular cancer and risk factors (cryptorchidism, dysgenetic
      gonads...) and extragonadic germ cell tumors. The authors review the risk
      factors. Chemotherapy is not sufficient to eradicate the CIS. A dose of 16 Gy of
      localized radiation is curative, excludes bilateral orchidectomy and preserves
      androgen function and azoospermic patient.

PMID- 9264762
TI  - [Contribution of computed tomography in the staging of upper urinary tract
      urothelial tumors. Importance of the tumor diameter measurement].
AB  - OBJECTIVES: To demonstrate a correlation between abdominal computed tomography
      (CT) data and the histological stage of upper urinary tract tumour (UUTT) in
      order to more accurately define therapeutic indications. MATERIALS AND METHODS:
      From 1984 to 1995, 51 patients were treated for UUTT and were assessed by
      preoperative abdominal CT. 41 of the 51 CT scans were considered to be
      interpretable and were reviewed retrospectively by a single radiologist. The CT
      stage and tumour diameter were compared to the pathological stage. RESULTS: CT
      staging had a reliability of 76%, by combining stages Ta-T2, which could not be
      distinguished. The sensitivity of CT to assess invasion of the renal parenchyma
      and ureteric or perirenal fat was 100% and 70%, respectively, with a specificity
      of 82% and 97%. The accuracy can be improved by decreasing the thickness of
      sections of the tumour. Tumour diameters (d) of pyelocaliceal tumours, measured
      by CT and pathology, were closely correlated (r2 = 0.83). All UUTTs less than 3
      cm in diameter were found to be superficial on histology. CT correctly estimated
      the size of these small tumours in 14/15 cases. Overall, by setting the limit at
      3 cm, CT was able to detect a superficial pyelocaliceal tumour with a specificity
      of 92% and a PPV of 93%; however, a CT size > or = 3 cm is not predictive of the
      histological stage of the lesion. CONCLUSIONS: CT is still imprecise for the
      staging of UUTT, as it cannot distinguish between Ta, T1 and T2 lesions, and is
      still not sufficiently reliable in the assessment of invasion of the
      periurothelial fat or of the renal parenchyma. CT measurement of the diameter of
      pyelocaliceal tumours can provide an argument in favour of the superficial nature
      of the lesion and therefore guide the therapeutic decision towards a conservative
      approach.

PMID- 9264763
TI  - [Intradiverticular bladder tumors. Five case reports].
AB  - OBJECTIVE: To define the diagnostic and therapeutic approach to intradiverticular
      bladder tumour. METHODS: Five cases are reported in which initial
      diverticulectomy was followed by cystectomy in one case, systemic MVAC
      chemotherapy in 2 cases and concomitant radiotherapy-chemotherapy (CRC) in 2
      cases. RESULTS: One patient has died (MVAC), one patient is in partial remission
      (MVAC) and three patients are in complete remission (1 cystectomy and 2 CRC).
      CONCLUSION: Intradiverticular bladder tumour is a disease with a poor prognosis,
      whose histological features require aggressive treatment. Concomitant
      radiotherapy-chemotherapy appears to be a useful alternative.

PMID- 9264764
TI  - [Peroperative radiotherapy in the conservative treatment of infiltrating bladder
      cancers].
AB  - OBJECTIVE: Descriptive analysis of an intraoperative radiotherapy protocol (IOR)
      in the context of conservative management of invasive bladder cancer. METHOD:
      From November 1988 to September 1994, 24 patients with invasive bladder carcinoma
      (20 T2, 3 T3) were included in this protocol consisting of: transurethral
      resection (TUR), neoadjuvant chemotherapy (M.V.C.) in 14 patients, external
      irradiation (x 18 MV: 48 Gy/24 F/5 weeks) with concomitant chemotherapy
      (cisplatin 30 mg/day-3 days-2 cycles during irradiation)-follow-up cystoscopy
      then surgery with IOR (E 9 MeV: 15 Gy). RESULTS: The global 3-year survival was
      69%. An invasive intravesical relapse developed in 3 patients (1 salvaged by
      cystectomy) and a superficial relapse occurred in 1 patient. One patient
      developed pelvic lymph node progression and 7 developed distant metastases. The
      early and late toxicity was acceptable with 3 cases of ureteric necrosis or
      stenoses resolving after medical treatment. CONCLUSION: This series shows
      encouraging preliminary results. IOR appears to be a technique well adapted to
      lesions of the fixed portion of the bladder.

PMID- 9264766
TI  - [Value of free/total prostate specific antigen in the early diagnosis of prostate
      cancer (study of 105 patients)].
AB  - INTRODUCTION: Prostate Specific Antigen (PSA) exists in the serum in several
      molecular forms which can be measured by immunoradiodetectable assays: free PSA
      and total PSA (which represent the sum of the free PSA and complexed PSA to alpha
      1 antichymotrypsin). Recently, the proportion of free to total PSA could enhance
      the ability to distinguish benign histologic conditions from cancer. MATERIAL AND
      METHODS: Serum samples of 105 patients (31 histologically confirmed prostate
      cancers and 74 histologically confirmed untreated benign prostatic diseases) were
      included in this study. The total and free PSA levels were determined using the
      PSA immunoradioassay of Tandem-R PSA and Tandem - R free PSA. RESULTS: When all
      subjects were included, both total PSA and the proportion of free to total PSA
      significantly differentiated between patients with prostate cancer and patients
      with benign histologic conditions (p < 0.01 and p < 0.005). However, in men with
      total PSA values between 4.0 to 10.0 ng/ml, the proportion of free to total PSA
      significantly differentiated between the patients with benign and malignant
      histological conditions (p < 0.04). The most interesting was the ability of the
      proportion of free to total PSA to distinguish patients with total PSA value
      between 4.0 and 10.0 ng/ml and normal digital examination (p < 0.001). With these
      values of PSA-T, a free PSA cutoff of 0.23 detected at least 90.4% of cancers and
      would eliminate 19.4% of negative biopsies. CONCLUSION: Measurement of the free
      to total PSA level improves specificity of prostate cancer screening in selected
      men with elevated total serum PSA levels between 4.0 to 10.0 ng/ml and normal
      digital examination, and can reduce unnecessary prostate biopsies with minimal
      effects on the cancer detection rate.

PMID- 9264765
TI  - [The VLAP system (Visual Laser Ablation of the Prostate): comparative study of
      the contact versus non-contact techniques in a series of 100 cases].
AB  - OBJECTIVE: To compare two contact and non-contact techniques using the VLAP
      system (visual laser ablation of the prostate). PATIENTS AND METHOD: From January
      1994 to April 1995, two groups of 50 patients were included in a randomized
      prospective study and were treated by the contact and non-contact laser
      technique, respectively. These patients presented with symptomatic BPH requiring
      transurethral electroresection. These patients were evaluated according to
      subjective (AUA score) and objective criteria (maximum flow rate, transrectal and
      suprapubic ultrasonography). ND:YAG laser energy was delivered by a Medilas 4100
      source via a lateral beam fibre. Objective success criteria were an improvement
      of the AUA score by at least 50% and of the maximum flow rate by at least 50%
      with a difference of 4 mL/s. The failure criterion was the need to perform
      complementary electroresection during the first 6 postoperative months. RESULTS:
      The mortality was 2% (cardiovascular causes), and the overall morbidity (first
      postoperative month) was 29%, with 21% of a vesical irritation syndrome, 6% of
      urinary tract infection and 2% of bladder clots. The global result at 12 months
      showed a statistically significant postoperative improvement of the subjective
      and objective parameters studied preoperatively (p = 0.0001). In the contact
      group, the AUA score, mean maximum flow rate and residual urine, which had
      preoperative values of 19.1, 9.1 mL/s and 141 mL, respectively, were equal to
      2.3, 15.6 mL/s and 45 mL at 12 months. In the non-contact group, the same
      parameters, which had preoperative values of 17.8, 9.2 mL/s and 87 mL,
      respectively, were equal to 3.8, 13.3 mL/s and 47 mL at 12 months. The results,
      evaluated as a function of objective success criteria, showed a 12-month success
      rate of 68% for the contact method and 61% for the non-contact method. The mean
      hospital stay was 6 days and the mean duration of bladder catheterization was 5
      days with the two techniques. During follow-up, 7% of patients required revision
      by electroresection, regardless of the technique used. CONCLUSION: this study
      demonstrated identical results for the contact and non-contact techniques using
      the VLAP system.

PMID- 9264767
TI  - [Effectiveness and tolerance of three month sustained release leuprorelin in the
      treatment of metastatic prostatic cancer (comparative, randomized, multicentric
      study].
AB  - OBJECTIVE: To establish the pharmacodynamic and safety equivalence between 2
      sustained-release forms of leuprorelin 11.25 mg and 3.75 mg, in the treatment of
      metastatic prostatic carcinoma. METHODS: 44 patients received subcutaneous
      injections of leuprorelin for 9 months (randomization: 2/l): either 11.25 mg
      every three months (n = 29) or 3.75 mg monthly (n = 15). Main criterion:
      centralized monthly assay of plasma testosterone (T). RESULTS: The equivalence of
      the 2 forms in terms of mean plasma testosterone was demonstrated (p = 0.002): 1
      month: T = 0.19 +/- 0.03 ng/ml; 3 months: T = 0.27 +/- 0.04 ng/ml. Exploratory
      analysis did not reveal any significant difference between the groups for the
      number of patients castrated at each visit or for the number of patients with all
      T values < or = 0.5 ng/ml, or for clinical responses or safety. CONCLUSION: The 2
      forms have a comparable efficacy and safety.

PMID- 9264768
TI  - [Survival of metastatic prostate cancer: 71 patients followed for seven to eleven
      years].
AB  - OBJECTIVES: To refine our prognostic evaluation and consequently our therapeutic
      strategy to disseminated prostate cancer. METHOD: A cohort of 71 patients with
      metastatic prostate cancer, recruited between 1981 and 1985, was followed for 7
      to 11 years. RESULTS: The surveillance of this cohort revealed the following
      median survivals: 32 months of overall survival. 1 year of clinical remission. 15
      months between onset of clinical resistance and death. However, very marked
      variations were observed around these median durations: 17% of patients died
      within one year and, in contrast, 30% survived for more than 5 years. CONCLUSION:
      Prognostic factors emerging from this study are the degree of differentiation of
      the primary tumour, and especially the size of the primary tumour. In some cases,
      this last factor could encourage the immediate coprescription of specific
      treatment of the primary prostatic tumour with endocrine therapy.

PMID- 9264769
TI  - [War wounds of the external genital organs].
AB  - During the 18 months of war in Croatia, from May 1991 to November 1992, 4425
      wounded persons were treated at Osijek hospital in Croatia. 115 (2.6%) had
      urogenital injuries, including 32 cases (27.8%) of genital lesions, which were
      treated immediately after treatment of the associated visceral lesions. A
      conservative surgical attitude was adopted allowing preservation of wounded
      testes in almost one half of cases. A free rectus abdominis aponeurosis flap on
      the defect of the tunica albuginea gave good immediate results, but its secondary
      distension altered the aesthetic result and impaired erection.

PMID- 9264770
TI  - [Malformations of Wolffian duct derived male genital organs (epididymis, vas
      deferens, seminal vesicules, ejaculatory ducts)].
AB  - OBJECTIVES: To analyse embryological phenomena, in order to define a practical
      approach to management. METHODS: The authors reviewed the files of eight boys
      with an abnormality of Wolffian duct derived genital organs, consisting of three
      cases of vas deferens agenesis, two of which were accompanied by homolateral
      renal agenesis, one case of ectopic vas deferens with contralateral renal
      agenesis, three cases of duplicated vas deferens and one congenital seminal
      vesicle cyst with renal agenesis. DISCUSSION: Congenital malformations of the
      epididymis consist of cysts and agenesis or partial atresia. Cysts essentially
      raise a problem of differential diagnosis. Treatment is only required in the case
      of severe discomfort. Vas deferens agenesis is the commonest lesion, an
      incidental finding in children. An experimental treatment is proposed in adults.
      Duplications, interdeferential communications and deferentomegaly are much rarer
      lesions. Seminal vesicle cysts are well visualized by transrectal ultrasonography
      and should be treated surgically. Lastly, ejaculatory ducts may present
      urethroseminal reflux or may be ectopic. CONCLUSION: The possibility of absent or
      ectopic vas deferens should be considered in the case of unilateral renal
      agenesis. Vas deferens agenesis justifies examination of the contralateral side
      and investigation to exclude renal agenesis. Congenital cysts of the epididymis
      only require surgery when they are symptomatic. The presence of ipsilateral renal
      agenesis should be investigated in the case of cystic dilatation of the seminal
      vesicle.

PMID- 9264771
TI  - [Malignant histiocytofibroma of the bladder. A case report].
AB  - Malignant histiocytofibroma of the bladder is a rare (16 cases reported in the
      literature) and very aggressive sarcoma. It is sometimes associated with a
      haematological malignancy. The authors report a case of malignant
      histiocytofibroma of the bladder in a 72-year-old haemodialysed woman with a poor
      general status. She had a history of chemotherapy and radiotherapy for
      gastrointestinal lymphoma 6 years previously. Treatment consisted of palliative
      cystectomy for bladder pain and haematuria. A massive pelvic and abdominal wall
      recurrence occurred two months after cystectomy and the patient died. The authors
      review the 16 cases of malignant histiocytofibroma of the bladder reported in the
      literature. Histiocytofibroma is a tumour which requires aggressive treatment
      with a combination of radical surgery and systemic chemotherapy.

PMID- 9264772
TI  - [An unusual complication of anterograde endopyelotomy: ureteral intussusception
      (a case report)].
AB  - Endopyelotomy has recently found a new place in the treatment of stenosis of the
      pyeloureteral junction, and it can represent a treatment of choice. We report an
      unusual case of antegrade ureteral intussusception after antegrade endopyelotomy
      in a 30 year-old young woman with a solitary kidney, which caused proximal
      ureteral obstruction. These intussusceptions were probably caused by double CH
      endoprosthesis. These iatrogenic injuries required surgical resection with
      calicoureterostomy.

PMID- 9264773
TI  - [Infiltrating bladder tumor in a renal transplant patient: cystectomy with
      prostatic conservation and enterocystoplasty].
AB  - OBJECTIVE: The principles of treatment of de novo bladder tumours in renal
      transplant patients are comparable to those applied in non-transplant patients.
      In the case of an invasive tumour, techniques can be used to restore urinary
      tract continuity after cystectomy. A case of cystectomy with enterocystoplasty
      for invasive bladder tumour in a renal transplant patient is reported. MATERIAL
      AND METHODS: An invasive urothelial bladder tumour was discovered in a 62-year
      old man, 3 months after a 2nd renal transplantation. Treatment consisted of
      cystectomy with prostatic preservation and nontubulized enterocystoplasty.
      RESULT: With a follow-up of 21 months after cystectomy, the patient is alive
      without recurrence. He is perfectly continent during the day, with normal sexual
      intercourse and no reflux or residual urine. Renal function is normal.
      CONCLUSION: Cystectomy with enterocystoplasty can be an effective treatment for
      invasive bladder tumour in renal transplant patients. This treatment ensures
      oncological control and acceptable comfort while preserving the transplant.

PMID- 9264774
TI  - [The pathological prostatic utricle: two case reports].
AB  - The prostatic utricle is a small vestigial diverticulum on the posterior surface
      of the prostatic urethra. It is considered to be pathological when it is
      abnormally dilated. The prostatic utricle is revealed by signs of vesical
      irritation and dysuria, sometimes associated with a retrovesical mass on
      examination. The authors report two cases of pathological prostatic utricle. The
      first case was an 11-year-old boy presenting with dysuria. Retrograde
      cystourethrography confirmed the diagnosis. The utricle was resected via a
      transtrigonal intravesical approach. The second case was a 25-year-old man who
      presented with dysuria associated with a pelvic mass. IVU and ultrasonography
      suggested a diagnosis of retrovesical cyst. This patient underwent incomplete
      resection of the utricle via a retrovesical approach. Based on a review of the
      literature, the authors emphasize the need to look for a prostatic utricle in a
      young subject presenting with dysuria, particularly in patients with a
      malformation of the genitourinary tract (hypospadias, renal agenesis). All
      pathological prostatic utricles must be treated surgically. The incision is
      transtrigonal in medium-sized utricles and transperitoneal in large utricles. The
      utricular cavity must be resected as completely as possible.

PMID- 9264775
TI  - [Transvaginal closure of the bladder neck in women with a neurogenic bladder and
      destroyed urethra].
AB  - Complete destruction of the urethra is one of the long-term complications of
      continuous bladder catheterization in women with advanced neurogenic bladder,
      resulting in a continuous urine leak around the catheter. This type of
      incontinence can be treated by closure of the bladder neck associated with
      suprapubic bladder drainage. Several approaches hve been proposed: abdominal,
      vaginal and mixed abdominal-vaginal. Each of these techniques is described,
      together with their results. Closure of the bladder neck decreases the nursing
      care, reduces the risk of perineal infectious and cutaneous complications and
      improves the patient's quality of life. Ileal urinary diversion is not always
      possible in these patients who often have a poor general status. Transvaginal
      closure of the bladder neck therefore constitutes one of the treatment options.

PMID- 9264776
TI  - [Peri-ureteral injections for stress urinary incontinence].

PMID- 9264777
TI  - [Legal problems in everyday urology].

PMID- 9264778
TI  - [Treatment of erectile disorders with androgens: When? How?].
AB  - Erectile dysfunction associated to low circulating androgens is characterized by
      a low testosterone due to hypogonadism of hypothalamic-pituitary or testicular
      origin. Long term androgen administration is unacceptable unless biology has
      demonstrated hypogonadism with a low testosterone level not related to
      hyperpolactinemia. Intramuscular testosterone or transdermal dihydrotestosterone
      can be used with a similar clinical effect but a different biological impact
      regarding aromatase activity. Whatever may be the type of androgen
      supplementation, one should use low dosage with frequent administration in order
      to obtain stable and physiologic plasmatic values. On account of androgen impact
      on prostate and cardiovascular system, careful pretreatment screening should
      eliminate an occult prostate cancer and a vascular thrombosis risk in a
      complaining and informed patient. Clinical and biological parameters should be
      periodically followed throughout androgen therapy.

PMID- 9264779
TI  - [Hemostasis and tests used to investigate it].
AB  - Under physiological conditions, in healthy subjects, there is a perfect
      equilibrium between coagulation activation and inhibition systems. During a
      surgical operation, dysfunction of the coagulation activation system, responsible
      for haemorrhage, can be induced by the extent of the anatomical lesions or the
      pre-existence of a quantitative or qualitative platelet abnormality and/or one or
      several plasma clotting factors. In contrast, the postoperative period is
      dominated by the risk of thrombosis and this risk is increased in subjects with a
      deficit of a coagulation inhibitory protein. The patient's haemorrhagic and
      thrombotic risk must therefore be evaluated prior to any surgical procedure. The
      information obtained by clinical interview concerning the patient's personal and
      family history, combined with a few simple clotting tests generally allows
      prevention of haemorrhagic or thrombotic accidents.

PMID- 9264780
TI  - [Anticoagulants and platelet aggregation inhibitors in urology].
AB  - Anticoagulants are widely used in the prevention of thromboembolic disease
      (particularly during the postoperative period) and in the curative treatment of
      deep vein thromboses. Two classes of anticoagulants are currently available:
      heparins (standard heparin, low molecular weight heparin) and coumarin
      anticoagulants. The choice of anticoagulant must take into account the clinical
      context (preventive or curative treatment), as well as the pharmacological and
      pharmacokinetic properties of the anticoagulant. This treatment requires
      laboratory monitoring adopted to the anticoagulant selected.

PMID- 9264781
TI  - Measuring the quality of health care: state of the art.
AB  - BACKGROUND: September 12-13, 1996, in Washington, DC, the Institute of Medicine,
      as part of its Special Initiative on Health Care Quality, held an invitational
      conference to illustrate exemplary quality measurement and to discuss the
      results. Patient reports, innovative uses of outcome measures for quality
      improvement, risk adjustment, assessment in integrated health plans and health
      care settings, clinical guidelines, and projects on disseminating information on
      quality measurement techniques and tools were among the topics represented.
      IMPROVING MEDICATION USE: Brent James described studies undertaken to reduce
      adverse drug events (ADEs). When implementing any measurement system where error
      is a possible factor, it is important to emphasize identifying problems for the
      purpose of learning, not judgment. Lucian Leape agreed that staff involved must
      feel that the purpose of the study is to examine system problems, not
      individuals' mistakes. David Classen described a nonproprietary computerized
      disease-management program designed to reduce ADEs in infectious diseases. "A
      QUALITY VISION": Robert Brook said that the relationship between cost or
      resources devoted to care and quality is not well understood and is certainly not
      simple. He also said that although investments in measurement strategies are
      needed to make them better, that doesn't mean we shouldn't attempt to use the
      measurements we have now. CLOSING ADDRESS: Mark Chassin said that the
      presentations at the conference provided evidence that should allow us to
      conclude beyond a reasonable doubt that quality can be measured-with a degree of
      scientific precision equal to that of most of the measures used to take care of
      patients every day.

PMID- 9264782
TI  - [Genetic therapy for hemophiliacs--therapeutic potential and technological
      limits].
AB  - Defects in the genes encoding the human coagulation factor VIII (hFVIII) and IX
      (hFIX) result in life-threatening haemorrhages and severe arthropathies. While
      haemophiliacs are currently treated by blood-derived factors or recombinant
      hFVIII and hFIX, a number of recent technical advances make the prospect of using
      gene therapy to treat such genetic diseases a realistic goal. Several gene
      therapy strategies have therefore been developed and evaluated in recent years.
      Most of the initial protocols were ex vivo gene transfer approaches in which the
      target cells (fibroblasts, keratinocytes, myoblasts, ...) were expanded and
      genetically-engineered in the laboratory and then implanted in the host. However,
      the complexity of most ex vivo gene therapy strategies, together with the
      disappointing results obtained in various animal models stimulated the
      development of more direct in vivo gene therapy protocols. In aiming to establish
      such an in vivo gene transfer protocol for haemophilia B, we constructed and
      tested in vitro and in vivo various recombinant adenovirus vectors expressing
      human FIX. Intravenous administration of this vector into various strains of
      immunocompetent and immunodeficient mice led to an efficient hFIX gene transfer
      in liver and lung. As a consequence, the hFIX protein was correctly produced and
      secreted at high levels in the blood of the treated animals. However, expression
      was transient in all immunocompetent mice, except surprisingly in C57B1/6
      animals. A systematic molecular and immunological analysis allowed us to identify
      the parameters that prevent the long-term in vivo expression of the human
      molecule and to improve the current adenovirus vectors.

PMID- 9264784
TI  - [Transgenic human thymopoiesis from retrovirally transduced umbilical cord blood
      hematopoietic stem cells: experimental studies in the SCID-hu mouse].
AB  - The gene encoding the CD2 mouse cell surface antigen was retrovirally transduced
      into cord blood CD34+ cells. On infection by culture at the contact of retrovirus
      packaging cells, the mCD2 marker was expressed by 30-40% CD34+ cells, that
      included the most primitive stem cell-enriched Thy-1+ and CD38- subsets.
      Accordingly, sorted cord blood CD34+Thy-1+ cells could be directly infected in
      the same conditions. mCD2- transgenic cord blood CD34+ cells were then used to
      reconstitute human fetal thymus implanted in SCID mice. Five to 8 weeks later,
      the mCD2 antigen was detected on approximately 10% of the human thymocytes
      repopulating the thymus grafts and the transgene genome was detected in graft
      cell DNA by Southern blot. These results demonstrate efficient gene transfer into
      primitive cord blood hematopoietic cells endowed with lymphoid potential and
      suggest gene therapy schemes in neonates suffering inherited or acquired-such as
      HIV infection-disorders of the T-cell lineage.

PMID- 9264783
TI  - [A model of congenital erythropoietic porphyria for gene transfer in
      hematopoietic cells].
AB  - CEP is a rare disease inherited as an autosomal recessive trait and characterized
      by an overproduction and accumulation of porphyrins in the bone-marrow. Because
      the predominant site of metabolic expression of the disease is the erythropoietic
      system, bone marrow transplantation represents a curative treatment for patients
      with severe phenotypes. This treatment can be considered in severe cases when the
      disease appears in the first few years of life. When bone marrow transplantation
      is not possible, gene therapy by transplantation of genetically modified
      hematopoietic cells is an attractive alternative for the future. In this report,
      we present the restoration of enzymatic activity and the metabolic correction of
      deficient cells in vitro after transduction with retroviral vectors. The future
      availability of a mouse model of the disease will permit ex vivo gene therapy
      experiments on the entire animal.

PMID- 9264785
TI  - [Modulation of alloreactivity using genetically modified T lymphocytes].
AB  - While effectively preventing graft-versus-host disease (GVHD), ex vivo T
      lymphocyte depletion of the graft unfortunately increases graft rejection and
      reduces the graft-versus-leukemia (GVL) effect after allogeneic hematopoietic
      stem cell transplantation. The ex vivo transfer of the herpes-simplex thymidine
      kinase (HS-tk) suicide gene into T-cells before their infusion with the
      hematopoietic stem cells, should allow for selective in vivo depletion of these T
      cells with ganciclovir (GCV), if subsequent GVHD was to occur. We have
      demonstrated that retroviral-mediated transfer of HS-tk and Neomycine resistance
      genes in T-lymphocytes, followed by G418 selection, results in T-cells
      specifically inhibited by GCV with no bystander effect. In a phase I study,
      escalating amounts of HS-tk expressing T-cells are infused in conjunction with a
      T-cell depleted marrow graft to allogeneic HLA identical recipients. Toxicity,
      survival alloreactivity and GCV-sensitivity of the gene-modified cells are
      monitored.

PMID- 9264786
TI  - [Development of an anti-HIV gene therapy based on the antiviral properties of
      beta interferon].
AB  - The aim of our work is to explore the use of IFN-beta for gene therapy in the HIV
      infection. Transduction of various HIV target cells with a retroviral vector that
      carries the Hu-IFN-beta coding sequence under constitutive low expression
      control, confers resistance to HIV without affecting cell replication or
      function. After transduction, lymphocytes from HIV-infected patients develop
      resistance to the endogenous virus, provided the cells are derived from
      individuals with a CD4 cell count higher than 200 per mm3.

PMID- 9264787
TI  - [From non-A non-B hepatitis to hepatitis C].
AB  - In 1974, the existence of hepatitis serologically distinct from hepatitis A and B
      was recognized. They were tentatively designated non-A non-B. They accounted for
      90% of post-transfusional hepatitis. During 15 years numerous studies failed to
      identify agent(s) responsible for these hepatitis. In 1989 the virus responsible
      for parenteral non-A non-B hepatitis was identified and named hepatitis C virus.
      Shortly after, the virus responsible for enteral non-A, non-B was also discovered
      (hepatitis E virus). During these 15 years, a 60% reduction of post-transfusional
      hepatitis was obtained both by the measures instituted to prevent AIDS
      transmission and by the introduction of surrogate assays (ALT levels and anti-HBc
      antibody).

PMID- 9264788
TI  - [Development of a biological diagnosis for hepatitis C].
AB  - The agent responsible of more than 80% of the parenterally transmitted non-A-non
      B hepatitis, designated hepatitis C virus (HCV), was identified in 1988 thanks to
      the isolation of the first cDNA reactive clone which was derived from
      experimentally infected chimpanzees RNA. The recombinant protein expressed from
      this clone located in the NS4 region of the HCV, allowed to establish the whole
      HCV-RNA sequence and to develop the first generation enzyme-linked immunoassays
      for detecting anti-HCV antibodies. Subsequently, other recombinant viral antigens
      derived from other HCV genome regions, were produced and used to develop second
      generation screening and confirmatory assays (1991). At least, thanks to a better
      presentation of the epitopes, since 1993 the performance of third generation
      reagents have been improved. Nevertheless, in spite of those modifications, the
      performance of both screening and confirmatory assays still needs to be improved.
      Moreover, in cases of difficulties of HCV infection diagnosis with serological
      tests, HCV-RNA detection with genomic amplification tools represents a useful
      alternative.

PMID- 9264789
TI  - [Descriptive epidemiology of hepatitis C virus infection in France in 1996].
AB  - This paper on the epidemiological aspects of the hepatitis C virus (HCV)
      infection in France presents the risk factors of the ways of contamination
      (transfusion, drug addiction, nosocomial, professional or sexual contamination,
      familial or mother-to-infant transmission). The estimated prevalence of HCV
      infection in France is comprised between 500,000 and 650,000 individuals, i.e.
      slightly above one percent of the French population. The epidemiological
      contribution of the study of HCV genotypes and the biological means evidencing
      HCV transmission are detailed, as well as the actual evolution of the HCV epidemy
      in France.

PMID- 9264790
TI  - [Judicial liability and blood transfusion--equity, opportunity?].
AB  - Blood transfusion centres are regularly sentenced to compensate for damages
      caused to individuals contaminated following a transfusion. Some blood
      transfusion centre directors and certain senior civil servants of the Health
      Ministry were sentenced by the repressive courts. This article explains how these
      solutions are not innovative and only result from the application of the rules of
      common law to transfusion activity. The author tries to assess the opportunity
      and equity of this.

PMID- 9264791
TI  - [Society and hepatitis C--knowledge, perceptions, and public action].
AB  - Despite its significantly higher prevalence, hepatitis C, now a serious public
      health problem, has long been overshadowed by HIV infection in France. The aim of
      this paper is to examine the factors that limit or prevent the conversion of
      scientific knowledge into public programs to tackle this transmissible viral
      infection. After an assessment of the knowledge currently available-quantitative
      data, routes of transmission, risk factors for hepatitis C and means of detection
      of HCV-we will analyse the interactions between the general public's
      representations and public decisions concerning detection, health care and
      prevention. Uncertainty concerning the sexual transmission of HCV makes a
      comparable mobilization to that observed in the case of the HIV infection
      improbable. It is necessary to target public measures at the different groups,
      both those at risk of contamination and those at risk of transmitting HCV, but it
      presupposes that answers can be found to the following questions: who can
      consider himself or herself at risk? What behaviours shape risk? Who is actively
      responsible for the risk when the HCV infection is transmitted? Better knowledge
      of the attitudes and perceptions of these specific groups and of risk-inducing
      situations will make public decisions more accurate in their contents and in
      their targets.

PMID- 9264793
TI  - [Western blotting in the serologic diagnosis of enterovirus infections. II.
      Detection of coxsackievirus antibodies in the sera of patients with suspected
      enterovirus infection and in paired specimens of sera and saliva].
AB  - Detection of anti-Coxsackie virus antibodies in sera with suspect enterovirus
      infection by the Western blotting (WB) method revealed complete agreement of
      results with virus neutralization tests (VNT) in those patients where in the VNT
      no antibodies against any of the tested Coxsackie viruses were detected.
      Comparison of the results of WB and VNT in other patients did not rule out an
      inter-type cross-reaction. In paired specimens of sera and saliva comparable
      results were obtained by WB, VNT and the complement fixation method. The rapid
      and relatively simple character of the WB method makes this method suitable for
      more detailed elaboration and introduction into routine diagnosis of enterovirus
      infections.

PMID- 9264792
TI  - [Western blotting in the serologic diagnosis of enterovirus infections. I.
      Detection of coxsackie virus antibodies in reference sera and sera of
      experimentally infected mice].
AB  - The introduction of rapid serological diagnosis of enterovirus infections is
      faced with the problem of inter-type cross-reactions. Therefore the method of
      choice is still the virus-neutralization test on cell cultures and on suckling
      mice resp., i.e. methods which are expensive and time consuming and demanding on
      laboratory equipment. The detection of antibodies against the Coxsackie virus by
      means of Western blotting revealed a specific reaction of commercial hyperimmune
      diagnostic rabbit as well as of sera obtained after oral infection of mice. The
      application of the method in the diagnosis of human enterovirus infections will
      be the subject of the subsequent part of this study.

PMID- 9264795
TI  - [Rhodococcus equi--a newly recognized opportunistic pathogen in man].
AB  - The review informs about substantial features of Rhodococcus equi with emphasis
      on the analysis of 115 as yet published and still expanding reports on the
      isolation of this zoopathogenic nocardioform actinomycete from man.
      Microbiological laboratories of human medicine have to learn not only how to
      identify R. equi but also recognize it as an opportunistic pathogen in particular
      in persons with the deficient immunity. R. equi is a gram-positive, encapsulated
      diphtheroid coccobacillus, partially acid fast. It grows well on common media,
      its colonies being after 48 hours characteristically mucoid, coalescing,
      irregular and mostly lightly pinkish. Biochemically it is little active,
      nevertheless it causes typical synergic haemolysis of erythrocytes influenced by
      staphylococcal beta-toxin. R. equi is found in soil and manure, especially in
      horse manure. It causes above all granulomatous pneumonia in young foals. In
      humans, it causes mostly pneumonia and lung abscess, more frequently in persons
      with immunity deficiency incl. AIDS, less often extrapulmonary abscesses, sepsis
      and wound infections. The disease are commonly chronic and recurrent. The ability
      of R. equi to persist in macrophages and destroy them is important in the
      pathogenesis of infection. In resistance to infection the cell-mediated immunity
      seems to be of major importance. The port of entry are the lungs, less often the
      alimentary tract or injured skin. About a third of the persons gives a history of
      contact with animals, manure or soil. The standard treatment is prolonged
      administration of a combination of rifampin and erythromycin. The isolation of R.
      equi is easy and if a laboratory suspects the presence of this microorganism, its
      identification is not difficult.

PMID- 9264794
TI  - [Media for transportation of specimens from gynecologic infections].
AB  - Specimens from the urogenital tract of 458 out-patients of the gynaecological
      clinic were examined using two collection kits including Amies and C.A.T. Swab
      medium. In the examined group, trichomonads were found in 165 cases (30.6% of all
      specimens), yeasts in 131 specimens (38.6%) and in 49 specimens (10.7%) both
      agents were detected. In 48 cases (10.5%), yeasts were detected only
      microscopically from the C.A.T. Swab medium. Examination of the wet mounts from
      C.A.T. Swab medium after 48 hours' incubation proved best for the diagnosis of
      trichomonads. Anaerobic bacteria were found in 378 specimens (82.5%), mycoplasmas
      and ureaplasmas in 281 specimens (61.4%). The simultaneous use of both media
      facilities detection of yeasts, trichomonads, aerobic and anaerobic bacteria and
      of mycoplasmas in specimens from the female urogenital tract.

PMID- 9264796
TI  - [Analysis of the incidence and routes of transmission of tularemia in Slovakia].
AB  - The morbidity from tularaemia in Slovakia has since the epidemic incidence in the
      sixties a declining trend. The mean annual morbidity rate declined from 5.5 per
      10(5) population in 1960-1969 to 0.3 in 1980-1994 and is markedly influenced by
      the incidence of tularaemia in the well known epidemic area in western Slovakia
      where in 1985 also the first cases of transmission of tularaemia by ticks were
      recorded in Slovakia. During the last decade (1985-1994) in Slovakia 126 cases
      were notified, out of them 96.8% in the western Slovakian region, more than half
      of the cases were recorded in the districts of Nitra and Nove Zamky. The analysis
      of the incidence of the disease in western Slovakia as compared with the previous
      decade (1975-1984) drew attention to marked changes in the epidemiology of
      tularaemia and a rise of the cases transmitted from other sources of infection
      than hares and by ectoparasites. Their ratio is almost 66%, from that 20.5%
      formed by cases transmitted by ticks (15.6%) and by other arthropods (4.9%). In
      the majority of patients with ticks in the case-history the ulceroglandular form
      of the disease was recorded (79%), with the primary affection at the site of the
      tick-bite, in the majority with lymphadenitis in the inguinal area (63.2%). The
      majority of the cases was recorded in summer, most frequently in occupational
      groups: pupils and students, forestry workers and mainly other occupations. The
      results of an epidemiological survey and data on the prevalence of for ticks
      infected with Francisella tularensis in the endemic area of Slovakia indicate
      that the tick-borne of tularaemia in humans Central European ecological
      conditions is probably more frequent than hitherto assumed.

PMID- 9264798
TI  - Controversies in staging and combined treatment modalities in lung cancer.
      Proceedings of the 4th IASLC Workshop on Therapy of Non-Small Cell Lung Cancer.
      Bruges, 23-27 June 1996.

PMID- 9264797
TI  - [beta-Lactam antibiotics--mechanisms of action and resistance in
      Enterobacteriaceae].
AB  - Beta-lactams are considered to be very important drugs used in the therapy of
      many serious bacterial infections. In the last few years, the number of isolated
      clinical strains from the Enterobacteriaceae family, mainly Enterobacter and
      Klebsiella spp. resistant to 3rd generation cephalosporins, rapidly increased.
      Resistance can be located on chromosomes or be determined by plasmids and
      transposons. The production of beta-lactamases is the most frequent manifestation
      of beta-lactam resistance. Spread of such resistance, especially plasmid-encoded,
      is believed to be a serious risk factor. Therefore the study of the resistance
      mechanism is Gram-negative bacilli to beta-lactams not only indicates the present
      situation, but also trends in future medical therapy.

PMID- 9264799
TI  - [Trends in alcohol consumption in relation to liver diseases in Slovakia 1973
      1994].
AB  - The World Health Organisation warns before the increase in alcohol consumption
      and the proportional increase in ethyltoxic diseases which have taken place in
      past decades. Slovakia is included into the countries with the highest
      consumption of alcohol in Europe. The authors present a retrospective analysis of
      alcohol consumption from 1973 to 1994 in Slovakia according to the kinds of
      alcohol beverages, in a selected district and according to profession and family
      status. The epidemiologic analysis of the situation of alcohol consumption that
      is currently present in Slovakia is based on the data from wholesale and retail
      sale in relation to the prevalence and the mortality due to hepatic cirrhosis.
      The presented data was investigated by the Slovak Statistical Institute and the
      Institute of Medical Statistics of the Slovak Republic. Mortality due to hepatic
      cirrhosis has increased during the past 40 years 10-fold in men, and 4-fold in
      women. A severely increasing trend in alcohol consumption which had taken place
      prior to 1990 was succeeded by an abrupt decrease in pure alcohol consumption
      after 1990 (as much as by 21.2%). This decrease corresponds with the proportional
      decrease in the prevalence of chronic hepatopathies (by 35%) and with the
      decrease in mortality due to hepatic cirrhosis (by 20%). This phenomenon may be
      explained by the proportional increase in prices of alcoholic beverages.
      According to average yearly consumption of pure alcohol (p.a.) per capita, the
      consumption of spirits dominates when compared with the consumption of beer and
      wine. It is desirable to continue in the begun decreasing trend in alcohol
      consumption which is crucial in the procurement of primary, secondary as well as
      of tertiary preventions on both individual and population levels. (Tab. 1, Fig.
      6, Ref. 19.)

PMID- 9264800
TI  - [Levels of Lp(a) and apolipoproteins in vegetarians and their informative value
      in hyperlipidemia].
AB  - BACKGROUND: An increased level of Lp(a) and unphysiological, even risk levels of
      apolipoproteins (apo) are currently considered to represent more significant
      markers of the premature development of atherosclerosis than that of increased
      serum lipids. AIM AND OBJECTIVES: The aim of our study was to detect the changes
      in Lp(a), apo A-I, apo A-II, apo B and lipids (TCH, TG, LDL-CH, HDL-CH, non HDL
      CH) levels in 54 middle-aged vegetarians (V). METHODS: In addition to
      vegetarians, 40 persons, all middle-aged workers of a chemical firm with
      hyperlipidaemia B and C (HLP) were examined. The control group was constituted of
      23 healthy people, normolipidaemics with common dietary patterns (K). Their age
      was mutually comparable within the examined groups. The apo A-I, apo A-II and
      Lp(a) levels were assessed by means of the radial immunodiffusion method, and apo
      B levels were detected by electroimmunoprecipitation method. RESULTS: The
      vegetarians yielded the lowest Lp(a) level, as well as an excellent lipid profile
      including apolipoproteins. The workers with HLP yielded significantly increased
      levels of apo B (p < 0.001), Lp(a) (p < 0.01), and values of the atherogenic
      index of apo B/apo A/I (p < 0.001) with simultaneous hypoapolipoproteinaemia apo
      A-I (p < 0.05) and apo A-II (p < 0.001). CONCLUSION: Physiological levels of
      lipids and apolipoproteins including the significantly lower levels of apo B,
      Lp(a) and levels of the index of apo B/apo A-I in persons with a high intake of
      fiber and minimal consumption of unsaturated fat give evidence of the decisive
      role of nutrition regarding the maintenance of optimal levels of lipids and
      lipoproteins and therefore represent the guarantee of protection from a premature
      development of atherosclerosis. (Tab. 1, Fig. 10, Ref. 11.)

PMID- 9264801
TI  - [The plasma profile of fatty acids in vegetarians].
AB  - The plasma profile of fatty acids has been observed in 27 vegetarian adults,
      their age ranging from 20 to 63 years (13 men, 14 women) with the average period
      of vegetarian dietary pattern being 8.8 years. A third of the men and a half of
      the women were lacto-vegetarians, the rest of them were lacto-ovo-vegetarians.
      The contents of saturated and monounsaturated fatty acids insignificantly
      decreased in vegetarians when compared with non-vegetarians (n = 26, 12 men, 14
      women, average group of non-smokers with mixed nutrition). The results of
      parameters regarded as positive factors in vegetarian diet and effective in
      prevention of atherosclerosis are as follows: significantly higher values of
      linoliec acid C 18:2, a significantly higher ratio of linoliec/leic acids C
      18:2/C18:1 and insignificantly higher value of linolenic acid C 18:3, together
      with an unchanged, or moderately decreased contents of poly-unsaturated fatty
      acids C 20:4 (arachidonic acid) and C 22:6 (n3; docosahexaenoic acid). Further
      prooxidative-antioxidative parameters were selected in regard to the theoretical
      anticipation of risk brought about by increased lipoperoxidation in vegetarians
      (poly-unsaturated fatty acids-substrate of the process) which is significant in
      the etiology of cardio-vascular and oncologic diseases. Their favourable values
      (significantly lower plasma contents of conjugated dienes of fatty acids,
      significantly higher plasma value of vitamin C, Beta-carotene, vitamin
      E/cholesterol-protection of LDL, vitamin E/triacylglycerols-protection of fatty
      acids, 3.5 times more significant positive linear correlation of vitamin
      E/triacylglycerol versus plasma contents of C 18:2) eliminate the risk of
      increased lipoperoxidation in vegetarians. (Tab. 3, Fig. 1, Ref. 29.)

PMID- 9264803
TI  - [Peroxisomal hereditary diseases].
AB  - Nearly two tens of diseases are known to be caused by impairment of several
      metabolic functions of peroxisomes, or by deficiency in individual peroxisomal
      enzymes. With the exception of X-bound adrenoleukodystrophy, all diseases are
      based on autosomally recessive type of inheritance and a majority of them are
      characteristic by specific neurologic symptoms. The group of diseases in which
      patients develop a generalised loss of peroxisomal functions includes:
      Zellweger's cerebro-hepato-renal syndrome, neonatal adrenoleukodystrophy,
      infantile Refsum's disease, hyperpipecolic acidaemia. Other diseases, such as
      rhizomelic chondrodysplasia punctata and Zellweger-like syndrome are accompanied
      by a deficiency in several enzymatic activities. X-bound adrenoleukodystrophy,
      pseudo-Zellweger's syndrome, hyperoxaluria 1, adult form of Refsum's disease and
      acatalasaemia are peroxisomal diseases with a deficiency of a single enzyme. In
      clinically most severe diseases (generalised loss of peroxisomal functions), the
      impairment of peroxisomal biogenesis is caused assumedly due to the defect in
      some of the peroxisomal membrane proteins. The biochemical findings are brought
      about by insufficiency in such metabolic functions as oxidation of fatty acids
      with very long chains, oxidation of the phytanic and pipecolic acids, synthesis
      of cholesterol, bile salts and plasmalogenes. Rhizomelic chondrodysplasia
      punctata and Zellweger's syndrome are more moderate forms which are dominantly
      biochemically manifestant by an impairment in the synthesis of plasmalogenes.
      Among the diseases characterised by a deficiency in individual peroxisomal
      enzymes, most frequent is the X-bound andrenoleukodystrophy which has several
      clinical phenotypes manifestant in childhood, as well as a clinically less severe
      form manifestant in adulthood-adrenomyeloneuropathy. The diagnosis of peroxisomal
      diseases is performed by use of a wide range of methods (morphological,
      biochemical, immunochemical and molecular genetic examinations) which enable both
      postnatal and prenatal diagnostics. (Tab. 1, Ref. 104.)

PMID- 9264802
TI  - [Determination of infravesical obstruction in men with benign prostatic
      hyperplasia using pressure-flow measurement and analysis with the Dx/CLIM
      software program].
AB  - BACKGROUND: Quantification of infravesical obstruction is important in the
      management of clinical benign prostatic hyperplasia (BPH). OBJECTIVES: The
      assessment of obstruction degree according to the urethral resistance parameter
      (URA) and bladder contractility (W) with software Dx/CLIM. METHODS: The study
      retrospectively analysed a group of 61 patients with BPH in order to assess the
      degree of obstruction and bladder contractility. Each of the patients underwent
      pressure/flow studies with Dx/CLIM analysis (URA < 29 cm H2O-unobstructed, Wmax >
      12.8 W/m2-normal bladder contractility) and symptom score evaluation (maximum 15
      points). In a dose-finding, placebo-controlled study 12 patients received 2 mg of
      doxazosin (alpha-1 blocker) and 11 patients received placebo during 4 weeks of
      treatment. RESULTS: 15 patients were unobstructed (25%) out of whom 10 had poor
      bladder contractility. Obstruction was present in 46 patients (75%) out of whom
      18 had impaired contractility. During treatment, the symptom score decreased
      statistically significantly in both groups (p < 0.05). URA decreased
      significantly only in the 2 mg group (2 mg group: baseline URA = 53.9, final mean
      URA = 40.1, p < 0.05; placebo group: baseline URA = 52.9, final mean URA = 56.1).
      Detrusor contractility was not significantly affected. CONCLUSIONS: Pressure/flow
      studies with Dx/CLIM analysis are very useful in the selection of BPH patients
      for treatment modalities and in the assessment of efficacy. Doxazosin decreases
      urethral resistance effectively. (Tab. 3, Fig. 3, Ref. 12.)

PMID- 9264804
TI  - [An unusual "black-dot" trichophytosis corporis in a man].
AB  - The authors describe an infectious disease, rarely occurring in the Slovak
      Republic-superficial trichophytia caused by Trichophyton tonsurans var.
      sulphureum-in a 37-year-old male patient with psoriasis. Untreated oval to
      circular foci 4-10 x 5-12 cm in size were localised on the forearms and knee,
      gradually developing black dots remaining after broken hair (parasitismus
      endothrix). After a failure in local and overall therapy by imidazole
      antibiotics, the peroral therapy by terbinafine (Lamisil) was successful. (Fig.
      2, Ref. 19.)

PMID- 9264805
TI  - [Saccharides and human health. Abstract of reports presented at a seminar held 24
      November 1995 in Prague and organized by ILSI Europe in cooperation with the
      Nutritional Research Institute in Bratislava and the 3rd Medical School of
      Charles University].

PMID- 9264807
TI  - [Localization of NADPH-d positive structures in the thymus of rabbits and rats].
AB  - In order to provide a morphological basis for understanding the role of nitric
      oxide (NO) in the thymus, present study was designed to clarify the localization
      and distribution of nicotinamide adenine dinucleotide phosphate-diaphorase (NADP
      d) activity, a marker of NO synthase in rabbit and rat thymuses. The NADPH-d
      histochemistry revealed a different distribution of diaphorase positive
      reactivity in both animal species, visible as dark blue structures. The rabbit
      thymus displayed lightly stained cortex, whereas medulla was seen as a rounded
      complex of intensively stained cells, without sharp demarcation between them.
      However, unlike the rat thymus, the NADPH-d positive cells appeared to be
      arranged in an irregular line of dense staining at the corticomedullary junction.
      In the rat thymus, the NADPH-d positive nerve fibres were not evident, whereas
      neuronal-like plexuses were seen in the perivascular topography of the rabbit
      thymus. These results suggest that NO may participate in the regulation of thymic
      function. (Fig. 6, Ref. 30.)

PMID- 9264806
TI  - [Levels of Cu, Zn, Se and their relation to levels of ceruloplasmin and the
      activity of antioxidative enzymes].
AB  - BACKGROUND: Essential trace elements copper, zinc and selenium are important
      parts of antioxidant enzymes as superoxide dismutase, glutathione peroxidase as
      well as of transport protein with antioxidant properties-ceruloplasmin. Mentioned
      trace elements may affect antioxidant defence system. AIM OF STUDY: The aim of
      our study was to estimate serum levels of copper, zinc, and selenium in a group
      of healthy subjects and to correlate them with erythrocyte activity of Cu,Zn-SOD,
      GSH-Px and serum levels of ceruloplasmin. METHODS: We examined a group of 128
      healthy volunteers (57 men and 71 women) aged 20 to 74 years. The analyses of
      trace elements we performed by atomic absorption spectrophotometry, Cu,Zn-SOD
      were detected by Randox test, GSH-Px by kinetic method and ceruloplasmin was
      measured immunoelectrophoretically. RESULTS: We have not found any correlations
      between investigated trace elements, age and sex. Average serum levels were as
      follows: copper (17.26 +/- 2.71 mumol/L), zinc (15.30 +/- 1.92 mumol/L), and
      selenium (0.79 +/- 0.19 mumol/L). There was a weak linear correlation between
      serum levels of copper and ceruloplasmin. CONCLUSION: There was no relationship
      between serum copper and zinc levels and Cu,Zn-SOD activity, and serum
      concentration of selenium and GSH-Px activity in the group of healthy subjects. A
      moderate linear correlation was estimated between serum values of copper and
      ceruloplasmin. (Tab. 2, Fig. 4, Ref. 29.)

PMID- 9264809
TI  - [Overview of the latest findings on nonclassical MHC antigens and activation
      pathways of T-lymphocytes].

PMID- 9264808
TI  - [Nutrition and Crohn's disease].
AB  - The relationships between non-specific inflammatory bowel disease and nutrition
      is considered. One of the hypotheses holds that environmental factors, especially
      those in dietary intake, can be the initiators of intestinal inflammation. In
      this connection authors examined a group of patients suffering from Crohns
      disease and ulcerative colitis. Results observed in patients with Crohns disease
      indicate: preferred consumption of flour products, decreased intake of vegetables
      and fruit, lowered tolerance to milk and milk products, increased sugar
      consumption, increased proportion of smokers, no differences in diet regimen
      between nick and healthy subjects. (Tab. 3, Ref. 16.)

PMID- 9264810
TI  - [Advances in DPX densitometry].
AB  - The author provides information on modern densitometric examinations and their
      development in the past three decades. He analyses in brief the possibilities of
      densitometry on the basis of the double x-ray absorptiometry on the basis of his
      own experience and data gained from literature. The current standard software
      equipment includes the measurement of the lumbal PA projection, lumbal lateral,
      coxae PA and entire body PA. The apparatus detects the quantity of minerals in
      bones in form of BMC (bone mineral content) and BMD (bone mineral density)
      values, and compares the measured values of density with the average values in
      the healthy population. It automatically evaluates statistical values of the Z
      and T score. The bone density can be measured with the accuracy of 3-5%, the
      error of reproducibility is 1-2%. The apparatus represents an ideal equipment for
      the measurement of bone density under normal anatomic conditions of the skeleton
      and in early stages of the disease which is manifestant by changes in bone
      tissue. As soon as the condition includes deformations of the skeleton and
      osteoproductive changes, especially osteochondrosis, spondylosis and the presence
      of osteophytes, the result becomes inaccurate. The study drafts the trend in
      densitometry in frame of therapeutic, preventive and research activities in
      orthopaedics. (Fig. 4, Ref. 16.)

PMID- 9264811
TI  - [Prevention of cardiovascular diseases: the Finnish experience and current
      situation].
AB  - 25 years ago Finland had the highest coronary mortality in the world. The North
      Karelia Project has carried out a coordinated, community-based intervention in
      order to reduce the prevalence of cardiovascular risk factors
      (hypercholesterolemia, smoking and hypertension). The evaluation has used
      standardized cross sectional population surveys at 5-year intervals. From 1972 to
      1992, among men aged 30-59 years, the prevalence of smoking changed from 52 to
      32%, the mean total cholesterol from 7.1 to 5.8 mmol/l, the mean blood pressure
      from 147/92 to 143/84 mmHg and the age-adjusted mortality rate has reduced for
      ischemic heart disease by 48% and for cancer by 42%. During the past 30 years the
      geographical distribution of cardiovascular mortality in Europe has substantially
      changed. The highest rates that were reported in the mid 1960's in Finland today
      occur in Central and Eastern Europe. The epidemy of cardiovascular disease in
      postcommunist countries seems to be only partially associated with high
      prevalence of the three "classical" risk factors (hypercholesterolemia, smoking,
      hypertension). It is probable that other, as yet unrecognized risk factors have
      potentiated the classical ones. Psychosocial stress and specific nutritional
      deficiencies of antioxidants leading to oxidative stress could belong to such
      "new" risk factors in Slovakia and in other postcommunist countries. (Tab. 2,
      Fig. 3, Ref. 36.)

PMID- 9264812
TI  - [Sleep-related breathing disorders--an interdisciplinary topic in undergraduate
      and postgraduate medical education].
AB  - Sleep-related breathing disorders (SRBD) include several disorders gradually
      developing from simple and loud snoring through upper airway resistance syndrome
      and sleep apnoea up to the Pickwickian syndrome. They are manifestant as a
      respiratory distress and apnoeic episodes, desaturation of oxygen in the blood
      and interruption of sleep. These symptoms are demonstrated in a case of a patient
      with the Pickwickian syndrome. SRBD may result in severe secondary life
      threatening cardiovascular complications (nocturnal arrhythmias, sudden cardiac
      death, stroke and pulmonary oedema). They may contribute also to the development
      of important disorders of public health such as hypertension, obesity, and
      traffic accidents resulting from hypersomnolence and fatigue. (Tab. 1, Fig. 3,
      Ref. 46.)

PMID- 9264813
TI  - [The role of endothelial nitric oxide in neurogenic contractions of the carotid
      artery in rabbits during cooling].
AB  - The role of endothelial nitric oxide in contractions induced by endogenous
      noradrenaline released by transmural nerve stimulation (TNS) and by exogenous
      noradrenaline (NA) was studied in isolated rings of rabbit carotid artery during
      cooling. At 37 degrees C, TNS produced frequency-dependent contractions of
      artery. Endothelium removal or inhibition of nitric oxide synthase by NG-nitro-L
      arginine methyl ester (L-NAME) significantly enhanced TNS-induced contractions.
      The magnitude of maximal contraction to exogenous NA was increased in L-NAME
      treated intact rings. Cooling the incubation bath from 37 degrees C to 26 degrees
      C increased the magnitude of neurogenic contractions in intact rings. L-NAME
      increased further the magnitude of neurogenic contractions at 26 degrees C in
      intact, but not in denuded arterial rings. Similarly, L-NAME increased
      contractions induced by exogenous NA during cooling. The results suggest that the
      response of the carotid artery to noradrenergic stimulation is modulated by
      nitric oxide originating from endothelial cells at normal as well as reduced
      temperature. (Tab. 1, Fig. 6, Ref. 19.)

PMID- 9264814
TI  - [Genetic polymorphism in sparteine oxidation--occurrence in healthy volunteers in
      Slovakia].
AB  - The aim of this study was to estimate the occurrence of the phenotype of poor
      metabolizers of sparteine (in the frame of sparteine-debrisoquine
      dextromethorphane polymorphism) in Slovakia. The authors examined a group of 216
      of healthy volunteers (73 women and 143 men, average age of the group 24, 9 +/-
      0.4 years), university students coming from various regions of Slovakia. The test
      substance-sparteine (1 x 100 mg tbl.) was administered perorally to all probands,
      in the evening after fasting. A 12-hour gathering of urine was subsequently
      performed. A sample of urine was subdued to examination. Isolation, separation,
      identification and assessment of the concentration of sparteine and its
      metabolites (2- and 5-dehydrosparteine) were performed by the method of gas
      chromatography. The metabolic MR ratio calculated from the ratio of the detected
      concentrations of sparteine and (2- and 5-dehydrosparteine) served for the
      assessment of the phenotype of poor (MR > 20), or rapid (MR < 20) metabolizers of
      sparteine in 8 authors found the poor metabolizer phenotype of 216 examined
      probands (i.e. in 3.75%). Its prevalence of the presented phenotype was lower
      than that anticipated on the basis of epidemiologic studies performed in other
      European countries. Study represents the first data on the phenotype of poor
      sparteine metabolizers in Slovakia. (Tab. 4, Fig. 1, Ref. 24.)

PMID- 9264816
TI  - [Asymmetrical body tilt induced by vibration of the Achilles tendon in patients
      with unilateral vestibular hypofunction].
AB  - Unilateral vestibular lesion results in postural balance deficits, which
      progressively vanish with time compensation. This functional recovery is caused
      due to the reorganization of the CNS structures and afferent inputs, mainly of
      the proprioceptive afferentation. Our aim was to determine the postural effect of
      leg proprioceptive input induced by the Achilles tendon (AT) vibration in
      standing patients with unilateral vestibular hypofunction. The examined patients
      (9 patients unilateral vestibular neuritis and 3 patients with Meniere's disease)
      had unilaterally decreased caloric responses. The control were 20 healthy
      volunteers with intact vestibular and motor functions. The postural responses
      evoked by AT vibration were evaluated by the symmetry of centre of pressure (COP)
      of the subject. The postural responses induced by the AT vibration in the healthy
      were bilaterally symmetrical. In the patients the body lean evoked by vibration
      on the side of intact vestibular apparatus was significantly decreased. The AT
      vibration on the lesioned side evoked practically identical response to the
      response of healthy subjects. In the repeated examination after 6 months the
      asymmetry disappeared which was in accordance with the recovered clinical state.
      The findings of asymmetry of postural COP displacement in patients with acute
      unilateral vestibular hypofunction documented transitory asymmetry of influence
      from leg proprioceptive inputs. The direction of decreased postural response to
      the proprioceptive stimuli was the same as pathological body lean of patient to
      the side of lesioned vestibular apparatus. This fact allows us to hypothesize
      that the postural responses evoked by leg proprioceptive inputs, directionally
      identical with the pathological body lean induced by asymmetry of vestibular
      afferentation are inhibited. (Fig. 3, Ref. 15.)

PMID- 9264815
TI  - [The effect of isradipine on lipid parameters in calcinosis in rats induced by
      vitamin D3].
AB  - BACKGROUND AND OBJECTIVE: The model of vitamin D3-induced calcinosis in rats
      makes it possible to follow important aspects of lipid and lipoprotein metabolism
      regulation not only in vessels, but also in the myocardium and in other organs of
      experimental animals. THE AIM of this paper is to follow the influence of
      isradipine on some lipid parameters in the serum, in aorta and myocardium.
      METHODS: D3 vitamin, isradipine, olive oil and the solvent for isradipine
      respectively were administered to experimental animals, males of Wistar rats. The
      animals of the control group (I) received olive oil in dose 0.5 ml/100 mg of
      bodyweight and the solvent for isradipine in dose 1 ml/100 mg of bodyweight. The
      second group (II) received D3 vitamin in dose 300000 i.u./kg of bodyweight. The
      third group (III) got pure isradipine in dose 0.25 mg/100 mg of weight and pure
      olive oil. The fourth group (IV) got D3 vitamin in the experimental same dose as
      the second group and a subsequent dose of 0.25 mg/100 mg of bodyweight. RESULTS:
      The animals were divided into 4 groups. The first group (I) were the controls.
      The second group (II) received D3 vitamin. We detected a significant increase in
      triacylyglycerol values by 12.4 per cent and in total lipids by 30.3 per cent,
      respectively an increase in triacylgycerols in myocardium by 188.8 per cent. The
      serum level of total cholesterol increased by 123.6 per cent and the level of LDL
      by 263.6 per cent. In the third group (III) the animals received only isradipine.
      In this group, the value of triacylglycerols in aorta decreased by 52.5 per cent,
      respectively and so did the total lipids by 22.4 per cent. The values of
      triacylglycerols in myocardium were decreased by 17.2 per cent and the total
      lipids by 6.2 per cent in contrast to the second group, where vitamin D3 was
      applied. The changes in the values of serum cholesterol were not significant. In
      the fourth group (IV) the experimental animals received vitamin D3 with
      isradipine. The values of total lipids and triacylglycerols were higher than
      these in group III, but in any of them did not attain the values of the second
      group, where only vitamin D3 was applied. CONCLUSIONS: The model of experimental
      calcinosis opens new possibilities of study of the pathomechanism of some
      manifestations of atherosclerosis, as well as the possibilities of their
      influence. Our results testify a positive influence of isradipine on the
      development of experimental calcinosis. (Fig. 4, Ref. 34.)

PMID- 9264817
TI  - [Use of gamma glutamyltransferase isoenzymes in the differentiation of chronic
      liver diseases].
AB  - Serum gamma-glutamyltransferase (GMT) is prevalently of hepatic origin, and its
      activity has long been known to be increased in most patients with hepatobiliary
      diseases. The different isoforms of GMT in serum, particularly those found in the
      course of hepatobiliary diseases, are associated with various lipoproteins. An
      important fraction of GMT activity is associated with apoprotein B in patients
      with icteric or anicteric cholestasis. We have studied the association of GMT
      activity with LDL and VLDL lipoproteins in patients with chronic liver diseases
      and the possibility to use this laboratory test in discriminating liver
      malignancies from other liver diseases. Thirty-eight healthy subjects, aged
      between 19 and 45 years, and 38 patients with liver cirrhosis, 7 with liver
      tumor, 16 with chronic active hepatitis and 5 with primary biliary cirrhosis were
      studied. Serum GMT activity complexed with LDL+VLDL was estimated according to
      Sacchetti et al. A cut-off of 40 U.l-1 of GMT complexed with VLDL+LDL results in
      a diagnostic sensitivity of 85% for liver tumor patients, and a diagnostic
      specificity of 87% and 65% towards the chronic active hepatitis or liver
      cirrhosis, respectively. According to our results, this test could be a useful
      contribution to laboratory tests that serve to discriminate chronic hepatopathies
      from liver malignancies. Our results are in agreement with the results published
      by Sacchetti et al. 1988, 167-172). (Tab. 1, Fig. 1, Ref. 15.)

PMID- 9264818
TI  - [Use of recording methods and sound analysis of cough in the study of sound
      phenomena associated with respiration].
AB  - The objective registration of the human body functions is one of the main tasks
      of the modern and prospective medicine. The registration of the heart, brain,
      muscles etc. activity have a long tradition. The registration of sound processes,
      for instance coughing was not solved completely despite their diagnostic
      importance. The authors worked out a new non invasive and precise method for
      cough sound registration and analysis which allows evaluation of the sound
      pattern, intensity and time duration. Application of this method for registration
      and analysis of the cry of new-borns gave rise to doubts about its suitability
      for an assessment of other sounds related to respiratory organs, except that of a
      cough. We registered and analysed the sound samples from Hirschberg's and
      Szende's (1982) sound archive for the purpose of the evaluation of the
      acceptability of the described method. The sound phenomena (109 samples of
      coughing, crying, barking and breathing) we transcribed from a record on a tape.
      The recorded signal was converted by A/D converter and analysed by computer by
      means of our own application programme. The sound and its pattern was transformed
      into a graphical record. This examination was completed by a sound frequency
      analysis based on the fast Fourier transformation with help of a computer
      likewise with our own application programme. It was found out that the used
      method reflected well the quantitative an qualitative differences of the
      evaluated sound samples. The graphical records reliably expressed the acoustic
      sound timbre as it shows the records of dog's and seelion's barking, cough, cry
      and cackling stridor of new-borns. The histographic curves which expressed the
      sound pattern showed a principally similar course. The intensity of sound
      examples was different. The sound samples duration were very often longer as the
      measurable time extent of software (0-819.2 ms) and therefore its evaluation was
      omitted. The repeated evaluation of the same sound phenomenon gave equal values.
      The spectrographic analysis confirmed the differences in sound samples. The
      values of the evaluated cough and cry sounds do not differ principally from the
      values registered in the previous author's observations. The results proved that
      the described method of cough sound registration and analysis was suitable for
      evaluation of different sound phenomena related to respiratory organs. (Fig. 3,
      Ref. 14.)

PMID- 9264819
TI  - [Mutagenic effects of coal tar used in the treatment of psoriasis].
AB  - BACKGROUND: Pharmaceutic tar used in the treatment of psoriasis has a high
      contents of polycyclic aromatic carbohydrates which are considered to be
      carcinogenic. AIM: The study is aimed at the estimation of the genotoxic risk
      arising from the treatment of psoriatic patients by pharmaceutic tar. The
      estimation is performed by biomonitoring. METHODS: The used methods included:
      bacterial test on TA 98 strain of Salmonella typhimurium aimed at the assessment
      of mutagenity of urine and cytogenetic test aimed at the assessment of
      chromosomal aberrations in peripheral lymphocytes. RESULTS: The exposition of
      psoriatic patients to pharmaceutic tar significantly increased the index of
      mutagenity as an index of the presence of mutagen in urine, as well as the
      occurrence of chromosomal aberrations in peripheral lymphocytes. CONCLUSIONS: The
      results of monitoring have indicated that psoriatic patients treated by
      pharmaceutic tar are endangered by an increased genotoxic risk. (Tab. 2, Ref.
      17.)

PMID- 9264820
TI  - [The fragile X chromosome syndrome: DNA analysis in families with familial
      occurrence of mental retardation].
AB  - The fragile X syndrome, the most common form of inherited mental retardation, is
      characterized by unique genetic mechanisms, which include amplification of a CGG
      repeat and abnormal DNA methylation. Direct DNA analysis of fragile X mutations
      has already shown its clear superiority for postnatal and prenatal diagnosis of
      the disorder and for carrier detection. In this, paper the authors report on the
      results of DNA analysis in families with familial mental retardation. They
      present the various alternatives (probe/enzymes combinations) for Southern blot
      based diagnosis and protocols which gave optimal results for detection of
      patients segregating for fragile X syndrome. Totally, 36 members from 10 families
      were analyzed by Southern blotting, including 18 mentally affected patients. No
      CGG expansion was detected in 9 clinically affected patients of 5 families.
      Expansion of the CGG repeats was found in 9 clinically and cytogenetically
      affected males, in 5 unaffected carriers of premutation, and in 1 carrier of full
      mutation in the remaining 5 families. Carriers represented mothers of the
      patients. These results correlated with cytogenetic and clinical expression of
      fragile X syndrome. The application of the method for diagnosis of the disease is
      discussed. (Tab. 2, Fig. 3, Ref. 21.)

PMID- 9264821
TI  - [Risk of cardiovascular complications in patients with type II diabetes mellitus
      in relation to serum triacylglycerols].
AB  - BACKGROUND: The importance of serum triacylglycerols (TG) as a risk factor of
      cardiovascular complications in non-insulin-dependent diabetes mellitus (NIDDM)
      patients has been emphasized in recent studies. OBJECTIVES: In the study of our
      group of NIDDM patients with and without coronary artery disease (CAD), it has
      been expedient to follow: 1. the difference in their serum TG, VLDL lipoprotein,
      total, HDL and LDL cholesterol levels, 2. dependence of other parameters on TG,
      3. to answer the question as to what extent the lowering of TG in NIDDM patients
      is expected to be decreasing the risk of CAD. METHODS: The investigated groups
      included the total of 39 NIDDM out-patients; 20 with manifest signs of CAD. The
      lipoproteins were measured using the BIO-LACHEMAR kits. MAIN RESULTS AND
      CONCLUSIONS: In CAD group, the serum TG and VLDL were significantly increased,
      HDL cholesterol being lower (p < 0.01, p < 0.01, p < 0.02, respectively). The TG
      to-HDL cholesterol, TG-to-total cholesterol ratios and atherogenic index (= total
      cholesterol-to-HDL cholesterol ratio) were in the CAD group also significantly
      higher (p < 0.02, p < 0.02 and p < 0.002, respectively). Furthermore, the serum
      TG was positively correlated with the atherogenic index and LDL (p < 0.001 and p
      < 0.05; r = 0.603 and r = 0.397, respectively). The logarithm of TG was a strong
      positive correlate of the total cholesterol (p < 0.001; r = 0.584). On the other
      hand, the serum TG was negatively correlated with HDL cholesterol (p < 0.005; r =
      -0.466). When logarithm of TG was taken, the statistical significance of all
      these correlations was even higher. The serum TG levels were significantly higher
      in patients with CAD. (Tab. 2, Fig. 7, Ref. 10.)

PMID- 9264822
TI  - [Endoscopic and surgical treatment of acute bleeding gastroduodenal ulcers].
AB  - One of the basic problems of the treatment of acute bleeding from gastroduodenal
      ulcers concerns the correct timing of individual therapeutic steps. From 1992 to
      1990 the I. Surgical Clinic in Brno performed the total of 438 urgent
      gastrofibroduodenoscopies, the most frequent finding being bleeding from the
      lesions in the area of the duodenal bulb. Endoscopic stoppage of bleeding was
      successful in 87.7% of patients. Failures in stopping the bleeding occurred in 18
      cases and lead to urgent surgical intervention. On the basis of gained experience
      we recommend the following algorhithm in patients with acute bleeding from
      gastroduodenal ulcers: urgent endoscopy-endoscopic stoppage of bleeding. Relapse
      of bleeding requires endoscopic control with a new attempt of endoscopic therapy,
      in the case of failure it is urgent to intervene surgically. (Tab. 4, Ref. 14.)

PMID- 9264823
TI  - [Surgical treatment of chiasmal gliomas in children].
AB  - Chiasmal gliomas are rare brain tumors occurring especially in children. Their
      proper treatment is still controversial and consists of surgery, radiotherapy and
      chemotherapy. Surgical removal of these tumors can usually be only partial or
      subtotal and radiotherapy frequently follows. There are supporters of surgical
      approach, as well as its enemies. The author has been engaged in problems of
      optimal treatment of this entity for more than 10 years. He is offering a review
      of knowledge from the literature concerning surgical treatment of this disease in
      children. The great majority of articles in the literature are dealing with
      retrospective analysis of relatively small series of patients usually treated in
      single neurosurgical department and the surgical treatment is enclosed like a
      part of combined therapy. Articles dealing only with surgical treatment of
      chiasmal gliomas are few and reviews determining the contemporary role of surgery
      of this entity are also lacking. This was the main impulse for writing this
      compilation. The short history of surgical therapy is reviewed. Some new trends
      of this therapy are also mentioned (microsurgery, Cavitron Ultrasonic Surgical
      Aspirator and peroperative use of visual evoked potentials). Up to date criteria
      for surgical treatment of chiasmal gliomas in children are given-exploration of
      chiasmal region and performing a biopsy in all cases, radical surgery only in
      extrinsic gliomas of the chiasmal region and conservative surgical approach to
      intrinsic chiasmal gliomas. It is emphasized that the significance of obstructive
      hydrocephalus in this entity has not been fully estimated till now, as well as
      the role of shunting procedures. Surgical treatment remains, nevertheless, an
      important armamentarium in the management of chiasmal gliomas in children. (Ref.
      20.)

PMID- 9264824
TI  - [Dr. Jan Fridrichovsky, the first Slovak professor of dentistry at Charles
      University Medical School].

PMID- 9264825
TI  - [Is the immune system our sixth sense? Relation between the immune and
      neuroendocrine systems].
AB  - There is an overwhelming evidence that cytokines, peptide hormones and
      neurotransmitters, as well as their receptors, are present in the brain,
      endocrine and immune systems. The structure and pattern of synthesis of these
      peptides by leukocytes appear similar to those synthesized in the neuroendocrine
      system, although some differences exist. Once secreted, these peptide hormones
      may function as endogenous regulators inside of the each system and also in
      bidirectional communication between the immune and neuroendocrine systems. Such
      communication suggest an immunoregulatory role for the brain and a sensory
      function for the immune system which may sense stimuli that are not recognized by
      the central and peripheral nervous systems (noncognitive stimuli). The plasma
      hormone concentrations contributed by lymphocytes usually do not reach the levels
      required when the pituitary gland is the source, but because immune cells are
      mobile, they have the potential to deposit the hormone locally at the target
      site. Several immunoregulatory cytokines, including IL-1, IL-2, IL-6, IFN-gama
      and TNF are produced not only in the immune system but in the neuroendocrine
      system as well. They have profound effects on neuroendocrine functions especially
      on hypothalamic pituitary axes. Neuroendocrine influences that modulate the
      immune function mainly include mental and physical stress. It can reduce the
      resistance of organism to infectious diseases and malignancies by compromising
      the immune system directly or indirectly. The brain is not an immunologically
      privileged site and therefore may become the target of immunologic attacks
      resulting in neuroimmunological diseases with an autoimmune component. The impact
      of psychological and psychosocial factors on the immune system is studied by
      psychoneuroimmunology whereas neuroendocrine immunology is generally interested
      in the interactions between the immune and neuroendocrine systems under
      physiological and pathological conditions. The recognition of the identity of
      ligands and receptors in the immune, nervous, and endocrine systems suggest a
      radically altered view of the immune systems impact on other tissues and organ
      systems, and vice versa. This will undoubtedly change our understanding of
      physiology, and consequently should profoundly impact the practice of medicine.
      (Tab. 5, Fig. 4, Ref. 85.)

PMID- 9264826
TI  - [Pathogenesis and therapy of multiple sclerosis].
AB  - Multiple sclerosis (MS) is one of the most frequent serious neurologic diseases.
      Etiologically, MS involves genetic, viral and other factors. The key pathogenic
      mechanisms reside in the autoimmune reaction of activated CD4+ T lymphocytes
      crossing the haematoencephalic barrier and attacking different epitopes of the
      basic protein and proteolipid of myelin sheaths. The damaging reaction involving
      activated macrophages, destructive inflammatory cytokines and toxic radicals
      leads to the development of disseminated plaques. The passage of autoimmune T
      lymphocytes to the brain tissue is facilitated by overexpression of adhesion
      molecules on endothelial cells, neural cells and immunocytes. The diagnosis of MS
      is based on characteristic changes in the blood and liquor, and on the results of
      modern methods, especially (gadolinium enhanced) MRI. The "classical" treatment
      is based on glucorticosteroids, azathioprine, cyclophosphamide and other
      chemicals which are not fully satisfactory and are accompanied by serious side
      effects. Therefore, attention will be paid to three prospective biological
      methods of treatment: 1) peroral application of bovine myelin, its fractions, and
      synthetic copolymer-1, aimed at the restoration of immune tolerance; 2)
      injections of natural and recombinant interferon-beta, interfering with the
      pathogenic IFN-gamma and other cytokines; 3) systemic enzyme therapy (residing in
      peroral application of combinations of animal and herbal hydrolytic enzymes),
      which modulates adhesion molecules and suppresses the activation of autoimmune T
      lymphocytes. The chief results of clinical studies with respect to the
      effectiveness and safety of these therapeutic methods, will be summarized. (Ref.
      34.)

PMID- 9264828
TI  - [Transmissible spongiform encephalopathies: neuroinfections with unconventional
      immune reactions].
AB  - Transmissible spongiform encephalopathies (TSE) as well as the properties of the
      major component of the infectious agent-prion, and the most important human and
      animal prion diseases are characterized. Considering the recent biochemical and
      molecular biological data, possible explanations of natural resistance, species
      barrier and lack of the immune response to the unconventional infectious
      particles are presented. Finally the importance of immunoblotting and
      immunostaining as the most specific confirmation of TSE diagnosis is underlined.
      (Ref. 11.)

PMID- 9264827
TI  - [Local immune defects--products of free oxygen radicals].
AB  - The discussion about the supporting task of four main active oxygen dependent
      mechanisms mediating and modulating immune signals was included in the work,
      along with the discussion on antioxidants influencing these mechanisms. The
      former include xanthine-oxidase, cyclooxygenase, lipoxygenase, aldehyde oxygenase
      metabolic chains. Currently, we are just beginning to realize that active oxygen
      and antioxidants can modulate the induction of physiological signals, and that
      these effects are not limited to the immune system. The effects of antioxidant
      treatment could represent neutralization of harmful radicals, albeit they can
      simply represent modulation of complex biochemical events which are essential
      parts of normal metabolism. Some natural antioxidants, e.g. alfa-to-copherol,
      ascorbic acid and beta-carotens are very good means of the primary prevention,
      but with acute failure of local antioxidants, they do not prevent the excessive
      production of proliferative inflammatory tissue. Tirilazad-mesylate has threefold
      beneficial influences: first as an inhibitor of the creation of oxygen radicals,
      second as a scavenger or quencher of free oxygen radicals, and finally in the
      arrangement of the defects in the phospholipid bilayer and possible receptors of
      macrophages, as well as T cells. The drug is suitable for active modulation of
      locally changed immune reactions and thus it rejects harmful proliferative
      inflammation in the subdural space. Until recently it has been eliminated by
      surgical procedure. The authors expel the thick (0.8 cm) subdural collection of
      the proliferative inflammatory product by tandem treatment which includes
      methylprednisolon+tirilazad-mesylate for three days, followed by fourteen days of
      methylprednisolon, which was gradually decreased in daily oral doses. This is a
      revolutionary change in the treatment of similar intracranial processes. (Fig. 4,
      Ref. 21.)

PMID- 9264829
TI  - [Spongiform encephalopathies (prionoses) in animals].
AB  - Spongiform encephalopathies constitute a growing group of diseases of the central
      nervous system which, contrary to other neurodegenerative processes, can be
      transferred experimentally from one animal species to another. They can develop
      spontaneously on a hereditary familial basis, the conform prion protein
      developing in the posttranslation process having the character of in infectious
      agent initiating the degeneration of nerve cells. The mechanism of such as
      infection differs from other infectious diseases. The bovine spongiform
      encephalopathy agent, discovered in Great Britain in 1985 has an extensive
      zoonosis potential and has overcome the interspecies barriers. The key problem in
      spongiform encephalopathies of animals is the definitive explanation of their
      etiology, pathogenesis, intravital diagnosis as well as interspecies
      relationships. (Tab. 5, Ref. 11.)

PMID- 9264830
TI  - [Immunopathogenesis of myasthenia gravis and the Lambert-Eaton myasthenic
      syndrome].
AB  - Myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) are
      autoimmune diseases manifestant a disorder of neuromuscular transmission. In MG,
      the autoimmune process is directed against the postsynaptic part whereas in LEMS,
      it is focused at the presynaptic part of this connection. Current immunological
      studies have confirmed the polyclonal and heterogenous characters of the
      autoimmune process. In patient with MG, the presence of antibodies against
      various epitopes of acetylcholine receptor, as well as against other muscular
      fiber protein (e.g. ryanodine receptor, titin, myosin, etc.) were confirmed.
      Patients with LEMS yielded antibodies against the proteins of various types of
      voltage-dependent calcium channels located in the presynaptic part of the motor
      nerve ending, as well as those against synaptotagmin. These findings indicate the
      necessity of a more complex immunological examination of patients in order to
      clarify both variability of clinical picture and prospective planning of specific
      immunotherapy. (Tab. 4, Fig. 3, Ref. 25.)

PMID- 9264831
TI  - [Down's syndrome--effect of increased gene expression in chromosome 21 on the
      function of the immune and nervous system].
AB  - Down syndrome (DS) is associated with mental retardation, immune disorders and
      congenital heart diseases. Although it is usually caused by the presence of an
      extra chromosome 21, a subset of the diagnostic phenotypic features may be caused
      by the presence of the band 21q22, called the "Down syndrome region". Many
      proteins important for the immune and nervous systems as CuZn-superoxide
      dismutase (SOD-1), CD18-beta chain of LFA-1, interferon receptor, APP-amyloid
      precursor protein, protein S-100 beta are coded by chromosome 21. Overexpression
      of these molecules may contribute to the thymic derangement that results in
      anomalous maturation leading to functionally impaired T cells. Many factors have
      been shown to contribute to the immune deficiency which results in high
      susceptibility to infections, high rate of malignancies, and autoimmune phenomena
      in persons with DS. The main disorders in the immune system include thymus
      abnormalities, changes in cell-mediated immunity, phagocytosis, antibodies
      mediated immunity and a high prevalence of autoantibodies in persons with DS.
      Furthermore, the duplication of chromosome 21 genes may generate most of the
      pathological changes in the central nervous system. There is an increased
      prevalence of seizure disorders. Such widespread alterations in the cortical
      areas seem to account for specific impairments observed in short-term and long
      term memory, language skills, and cognitive and learning processes. If all
      principles of optimal health care and adequate education were followed without
      exception for persons with DS, then the quality of their life could be improved
      significantly and they would be able to become productive citizens in the
      society. (Tab. 5, Fig. 3, Ref. 42.)

PMID- 9264832
TI  - [Epileptic seizures and immune disorders].
AB  - The links of epileptic seizures with febrile diseases, as well as with common
      infections are generally known. Similarly, physicians are aware of the
      coincidence of epileptic activity with immunity disturbances, as well as of the
      effects of the antiepileptic drug phenytoin on the immunity system. Disturbances
      of immunity are commonly reported in 30% of the population. Our clinic is a
      consilliary regional centre for torpid epilepsies and sleep defects. The aim of
      study is to document the occurrence of immunity disturbances in unsuccessfully
      treated patients (5-25 years of age) with generalised convulsive epilepsy
      (GENKONV-GK) in a group containing 50 patients, and with partial epilepsy with
      complex symptomatology (PARTKOMP-PK) in a group containing 75 patients. At the
      same time, this studys objective resided in seeking evidence of the positive
      effect of immunomodulatory therapy. In all patients, the basic diagnosis had been
      stated in coincidence with the origin of epilepsy during hospitalisation in
      neurologic wards. In 1993-1995 our clinic supplemented the electrodiagnosis by a
      series of routine EEG which was focused at the recurrence of the disease. As a
      rule, each of the patients was subdued to a 24-hour EEG monitoring on the 12
      canal apparatus. Individual supplementation by CT, MR and USG of the brain, the
      arrangement of anti-epileptic therapy and basic immunological examination were
      made during the first year of investigation. Still, after the stabilisation of
      anti-epileptic therapy (monitoring) and indicated immunomodulatory therapy was
      added. RESULTS: The immunologic examination was negative in 4 patients, all being
      members of GENKONV group. Atopy was found in 56% of GK group, and in 65% of PK
      group. Disturbances of specific cellular immunity were revealed in 80% of the
      patients of the GK group, and in 85% of PK group. The signs of inflammatory
      activity and other signs of allergy were present to a lesser extent. CONCLUSIONS:
      Out of the amount of 125 patients only 3.2% yielded no disturbances of immunity.
      The application of immunomodulatory therapy appears to represent a promising
      supplementary-stabilisation therapy. (Tab. 2, Fig. 4, Ref. 5.)

PMID- 9264834
TI  - [Disability among the population of the Russian Federation].
AB  - The prevalence and structure of invalidity in the Russian Federation is analyzed
      on the basis of statistical records of the Russian State Committee for
      Statistics. Dynamic analysis of parameters and territory ranging were used for
      statistical data processing. Recommendations on social and labor rehabilitation
      of disabled subjects are offered.

PMID- 9264833
TI  - [Immunomodulatory therapy of epilepsy with transfer factor].
AB  - Effect of immunotherapy with Transfer factor administered for a period of three
      months was studied in a group of ten epileptic patients, treated with
      carbamazepine or primidon previously and throughout the study. Out of eight
      patients, who finished the study we could notice significant reduction of
      epileptic discharges in eight patients. The results of this study prove that
      addition of immunomodulatory treatment to patients with intractable epilepsy
      could substantially improve the course of the disease in some patients. (Tab. 1,
      Fig. 5, Ref. 13.)

PMID- 9264835
TI  - [The control of quality and efficiency of medical assistance at a clinic of a
      medical institute].

PMID- 9264836
TI  - [Contemporary quality control of inpatient care according to the survey].
AB  - A sociologic survey was carried out in one of the large multi-profile hospitals
      of St. Petersburg. A total of 220 questionnaires were distributed. The
      questionnaire included twenty signs by which the respondents assessed the quality
      of medical care and expressed their opinion on how it may be improved.

PMID- 9264837
TI  - [On territory-related system of health care quality control].

PMID- 9264838
TI  - [The current problems in quality control of health care provided for the
      population].

PMID- 9264839
TI  - [On the problem of health care quality control].

PMID- 9264840
TI  - [The main approaches to reducing cardiovascular morbidity and mortality in
      Russia].
AB  - Analysis of medical statistical data and of the socioeconomic situation in the
      country brought the authors to a conclusion that at present the principal factors
      responsible for cardiovascular diseases, specifically, coronary disease and
      cerebrovascular disorders, are environmental factors, such as chronic stress,
      alcoholism and hard drinking, violation of social and hygienic norms of labor,
      and a number of factors related to medicine: no prophylactic check-ups and
      unavailability of effective drugs. "Internal risk factors" should not be
      disregarded as well: hypercholesterolemia, arterial hypertension, etc. Based on
      their results, the authors propose measures aimed at limitation of overall stress
      exposures, alcoholism and hard drinking control, sociohygienic labor protection,
      re-creation of a system of effective prophylactic check-ups, and making present
      day effective drugs available for the population.

PMID- 9264841
TI  - [The organization of a continuous quality control of health care at a multi
      specialty inpatient clinic under the system of comprehensive medical insurance].

PMID- 9264842
TI  - [Increasing quality control in Russia's health care system: new goals and new
      means].
AB  - Presents a territorial system for controlling the quality of medical care
      rendered in the district, which helps not only react to the final results of
      medical service (reaction to a detected defect), but rather prevent the flaw. A
      programmed purposeful approach to the creation of a system for quality control
      helps it integrate in the universal system of public health management both at
      the territorial and municipal level.

PMID- 9264844
TI  - [The organization and technology of interaction between health care clinics and
      comprehensive medical insurance].
AB  - Presents the results of realization of public health reforms in some regions of
      the country. Describes the scheme and stages of introducing obligatory medical
      insurance, the tasks, functions, and interests of various managing structures of
      a territory in the progress of reforms. Offers experimentally developed criteria
      for assessing the readiness of a territory to introduction of obligatory medical
      insurance, describes the methods and order of monitoring the quality of medical
      care rendered to insured patients, and outlines alterations in the organization
      and legal status of public health institutions.

PMID- 9264843
TI  - [The diagnostically related system of groups as the instrument of the estimated
      cost of inpatient care under the the system of medical insurance].
AB  - Analysis of data base for 73,000 patients treated at various hospitals of the
      Novgorod district demonstrated the efficiency of the system of diagnostically
      related groups and the "American" cost weight coefficients for assessing the
      resource requirements of each hospital with due consideration for the inpatient
      populations; moreover, such an approach is useful in dealing with insurance
      organizations in connection with each patient treated. The cost weight
      coefficient was found to be in good correlation with the diagnostic and
      therapeutic expenditures and less dependent on the duration of hospitalization.

PMID- 9264845
TI  - [Public health care reform and its organization].

PMID- 9264846
TI  - [The teaching of a course on medical theory at a medical department of Moscow
      University].

PMID- 9264847
TI  - [Folk hygiene (historical- medical evaluation)].

PMID- 9264848
TI  - [A historical analysis of financial resources provided for the system of
      comprehensive medical insurance].

PMID- 9264849
TI  - [The role of military physicians of the Soviet Army in studying endemic diseases
      in the Far East].

PMID- 9264850
TI  - [A monument to doctors on the Karse].

PMID- 9264851
TI  - [The urbanization and demographic structure of population].
AB  - Analyzes the effects of urbanization on the demographic structure of population.
      An increase in the degree of urbanization was found to be paralleled by an
      increase of the age qualification and of the migration activity of the
      population. The national composition of the population does not depend on
      urbanization.

PMID- 9264852
TI  - [On longevity among the population of Siberia and the Far East].
AB  - Demographic values of longevity have been calculated on the basis of population
      census data and mortality tables. Analysis of the present-day level of longevity
      in Siberia and Far East and its time course in 1979-1993 is presented. Regular
      reduction of longevity parameters from West to East and lower values of these
      parameters in comparison with the rest of Russia have been revealed. Negative
      shifts in the levels of longevity over the period of 1979 to 1993 have been
      observed for all regions of Siberia and Far East.

PMID- 9264853
TI  - Partnering. The invisible field of hope, potential and discovery for the work
      setting.

PMID- 9264854
TI  - [Intestinal foreign body with sigmoid perforation in an area of carcinomatous
      stenosis: incidental finding or etiology?].
AB  - Ingestion of a foreign body is a common incident. In most cases it rarely
      produces symptoms, but sometimes may cause severe complications such as abscess
      formation, obstruction or perforation. A definite diagnosis can be difficult to
      obtain for the following reasons: 1. the past history doesn't give any clue; 2.
      the symptoms are veiled by another intestinal disease; 3. radio opaquity of the
      foreign body is absent; 4. complications can mimic different symptoms inspite of
      their unique etiology. The following case reports a patient with an intestinal
      perforation, where a foreign body and a stenosis, caused by a sigma neoplasm,
      were simultaneously present. Histological findings showed that the foreign body,
      not the neoplasm, was causing the perforation, whereas for the underlying disease
      it only was an incidental finding.

PMID- 9264855
TI  - [Gastrointestinal hemorrhage and diverticula of the jejunum--presentation of a
      case report and review of the literature].
AB  - Gastrointestinal bleeding due to jejunal diverticulosis is an uncommon emergency
      condition that has been encountered recently in one patient. The case of this
      patient treated with an emergency laparotomy and a segmentary small bowel
      resection is here presented. The clinical significance, proper diagnostic
      evaluation, and treatment of the hemorrhagic complication of jejunal diverticular
      disease are reviewed.

PMID- 9264856
TI  - [Value of Hartmann's operation as an emergency intervention in sigmoid
      diverticulitis].
AB  - INTRODUCTION: Improvements in antibiotic and intensive care treatment have
      facilitated the conservative therapy of patients suffering from complicated
      diverticulitis of the sigmoid for the time necessary for preparation in view of
      early elective resection of the sigmoid colon. Consequently, early elective
      resection of the sigmoid colon with primary anastomosis has become very popular
      as the treatment of choice in complicated diverticulitis. This has led us to a
      retrospective evaluation of our own results with both Hartmann's operation and
      resection with primary anastomosis. PATIENTS AND METHODS: 55 patients with
      complicated diverticulitis of the sigmoid colon were operated on at our
      institution between 1981 and 1990. Group I consisted of 33 patients (17 females
      and 16 males) aged 39 to 89 years who underwent Hartmann's operation. Group II
      included 11 patients (6 females and 5 males) aged 39 to 85 years treated by
      resection and primary anastomosis. The remainder of the patients was treated by a
      three-step procedure and should not be considered here. RESULTS: In group I 25
      patients (76%) suffered complications either at the Hartmann's operation or at
      descendorectostomy or both. Mortality was 6%. Only 76% of patients had their
      stoma closed after an average of 3.8 months. The average hospital stay of both
      operations combined amounted to 61 days. In group II 3 patients had
      complications, one of which was lethal (lung emboly). The total hospital stay in
      this group averaged 22 days. CONCLUSIONS: For Hinchey stages I and II
      conservative treatment, bowel preparation and early elective resection with
      primary anastomosis should be attempted. In cases of general peritonitis (Stages
      III and IV) Hartmann's operation is still the treatment of our choice.

PMID- 9264857
TI  - [Results of anal sphincteroplasty in fecal incontinence--significance of intra
      anal ultrasound imaging].
AB  - The aim of the study was to evaluate the clinical, manometric and endosonographic
      results of overlapping sphincteroplasty for traumatic sphincter defects
      documented by endosonography. PATIENTS AND METHOD: We performed an overlap repair
      in 10 women aged 34 to 68 with fecal incontinence due to sphincter defects after
      obstetric (n = 8) or iatrogenic (n = 2) trauma. The fecal incontinence was graded
      using the Miller Score (0-18 points). Manometry and endosonography were done pre-
      and postoperatively. The mean follow-up time was 17 months (6-25 m.). RESULTS:
      Perioperative morbidity was low: one temporary colostomy was necessary due to an
      anal fistula. Eight out of 10 patients were satisfied with the result. The
      incontinence grade fell from an average of 14 points (8-17 points) preoperatively
      to 5 (0-12 points) postoperatively. The mean resting pressure increased from 36
      to 41 mmHg, the voluntary contraction from 48 to 59 mmHg. Endosonography allowed
      the precise localization of the defect before operation and the sphincteroplasty
      could be visualized after operation in all the patients. CONCLUSIONS: The
      overlapping sphincteroplasty improved fecal incontinence successfully in 9 of 10
      patients with posttraumatic sphincter defects. Endosonography is very useful in
      localization of the sphincter defect and documentation of the performed
      sphincteroplasty.

PMID- 9264858
TI  - [Necrotizing fasciitis cause by beta-hemolytic streptococci with fatal outcome--a
      case report].
AB  - The authors report two cases of necrotizing fascilitis (NF) occurring after
      surgical interventions on the breast (reduction mammoplasty in one patient and
      mastectomy for breast cancer in the other). In both cases the etiologic agent
      were group A pyogenic streptococci and both patients died. NF caused by hemolytic
      streptococci is a highly lethal disease (over 70% in literature). It starts
      typically with a purple lesion of the skin, followed by necrotizing fascial
      infection with secondary necrosis of the overlying skin and rapid progression to
      septic shock and multiorgan failure. This development is characteristic for NF
      and allows, together with microbiological results, to distinguish NF from other
      necrotizing soft tissue infections. Early recognition and aggressive surgical
      debridement are the mainstays of successful management. Antibiotics and intensive
      care therapy are indispensable. Hyperbaric oxygen or other supportive therapies
      do not lower death rate.

PMID- 9264859
TI  - [Endoscopic pre-peritoneal prolene mesh-plasty for management of inguinal and
      femoral hernias].
AB  - From October 1994 to March 1996 158 inguinal or femoral hernias were repaired in
      124 patients through a total extraperitoneal approach. The repairs were done with
      polypropylene mesh. The patients were seen 6 to 8 weeks postop; until today 57
      patients were seen 12 months postop. This method favours an early return to work.
      Patients with unilateral hernias returned to work after an average of 14 days,
      patients with bilateral hernias after an average of 19 days. Complications were
      rare and mostly minor. So far we have seen no recurrences and no mesh related
      complications. We consider the laparoscopic extraperitoneal mesh repair a safe
      procedure for inguinal and femoral hernias.

PMID- 9264860
TI  - [Cost increase due to incorrect antibiotic prophylaxis in visceral, thoracic and
      vascular surgery].
AB  - We analysed retrospectively 460 patients treated between March 1991 and February
      1992, in respect to a correct perioperative antibiotic prophylaxis. In our
      opinion a correct prophylaxis is a single-shot application, with a second dose
      given only during long operations (over 3 hours) or when blood loss is great. 240
      of the 460 patients analysed (52.2%) were given antibiotics prophylactically. In
      76.6% of the cases (n = 184) the prophylaxis was performed correctly. In 23.4% (n
      = 56) antibiotic application was extended indiscriminately into the post
      operative phase. This calculated to costs three times higher than those actually
      necessary, causing us to spend 22,000-Swiss francs unnecessarily, one twelfth of
      the total cost of antibiotic treatment in our hospital each year. For economic
      reasons as well as to keep growth of resistant strains in check, an antibiotic
      prophylaxis should be restricted to the perioperative period in most cases as a
      single shot only.

PMID- 9264862
TI  - Robert Huber--a life devoted to protein structures and functions.

PMID- 9264861
TI  - [Coronary artery bypass grafting without cardiopulmonary bypass: angiographic
      evaluation of a preliminary experience].
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) without cardiopulmonary bypass
      has been proposed to decrease morbid events related to the circuit and the blood
      pump. OBJECTIVE: To evaluate quantitatively coronary anastomoses with CABG
      without cardiopulmonary bypass. SETTING: Between February and December 1996, 19
      patients underwent CABG, through a median sternotomy in 12 patients and an
      anterior minithoracotomy in seven patients. Twenty internal thoracic artery
      grafts and seven saphenous vein grafts were studied by quantitative angiography
      in the immediate postoperative period (4 +/- 2 days). Diameters of native
      coronary arteries and grafts were analyzed by computer. PATIENTS: Patients
      averaged 57 +/- 8 years of age, with triple vessel coronary disease in three
      patients, double vessel disease in nine patients and single vessel disease in
      seven patients. Twelve patients underwent a single thoracic artery graft to the
      left anterior descending artery and seven patients underwent a double graft to
      the anterior descending and the right coronary artery. RESULTS: Hospital stay
      averaged 5 +/- 2 days, operating time averaged 144 +/- 30 mins and ischemic
      occlusion of the left anterior descending coronary artery averaged 20 +/- 8 mins.
      Serum creatine kinase MB fraction averaged 11 +/- 7 U/L and 25 +/- 37 U/L, 1 and
      24 h, respectively, after surgery. Diameter stenosis of the native coronary
      artery averaged 19 +/- 26% proximal to the anastomosis, 36 +/- 31% distal to the
      anastomosis and 27 +/- 32% at the anastomotic site of internal thoracic artery
      grafts. One native coronary artery distal to the anastomosis was occluded and an
      occluded anastomosis was reopened by percutaneous angioplasty 72 h after surgery.
      Saphenous vein grafted to the right coronary artery had only minimal stenosis at
      anastomotic sites. CONCLUSION: This initial experience with CABG without
      cardiopulmonary bypass suggests that adequate coronary anastomosis can be
      performed in selected patients.

PMID- 9264863
TI  - Non-ionic monomers and dimers: renal safety.

PMID- 9264864
TI  - Quiz case of the month. Villous tumor of the duodenum.

PMID- 9264865
TI  - Arteriosclerosis prevention by risk prevention. Symposia proceedings. January 13,
      1996, Munich and March 9, 1996, Nuremberg, Germany. Dedicated to Prof. Dr. med.
      Peter Schwandt on the occasion of his 60th birthday.

PMID- 9264867
TI  - [Endocrinology 1995-1996].
AB  - In a brief review of advances in endocrinology in the last two years the author
      discusses above all the vain expectations of a drug against obesity-the adipose
      tissue hormone leptin. Its elevated blood level in human obesity indicates that
      its secretion depends on the mass of adipose tissue and it is not certain whether
      leptin reduces the food intake in humans. Perhaps resistance to leptin is
      involved. New receptor diseases were revealed: mutation of LH receptors leads in
      both sexes to hypogonadism. Mutation of the calcium receptor in parathyroid cells
      leads to familial hypocalciuric hypercalcaemia or autosomal dominant
      hypocalcaemia. The complex regulation of the tonus of the vascular wall by
      endothelins is still the object of interest. Aquaporin is a renal protein which
      mediates the action of vasopressin. In the sphere of stress evidence is emerging
      on the participation of CRH in brain activity and the possibility to influence
      autoimmune inflammations and perhaps even AIDS by interference with the CRH
      proopiomelanocortin-ACTH-cortisol system.

PMID- 9264866
TI  - [Homosexuality in the medical context].
AB  - The author presents a review of contemporary views on homosexual orientation. He
      describes the development of attitudes of society and specialists and the gradual
      decriminalization and demedicinalization of homosexuality. Despite the modern
      trend of complete social acceptance of the homosexual minority it is important to
      deal with the peculiar features in social adaptation of these people. Homosexual
      men and women have their specific health problems: for instance quite
      understandable difficulties with the acceptance of their different sexual
      character. Homosexual men have a greater tendency of risky sexual behaviour which
      has epidemiological consequences in the incidence of sexually transmitted
      diseases and HIV/AIDS.

PMID- 9264868
TI  - [Comparison of the effectiveness of 17-beta-estradiol and calcitonin in women
      with postmenopausal bone loss].
AB  - BACKGROUND: The objective of this study was to compare effects of 17 beta
      estradiol and intranasal salmon calcitonin on bone mass and biochemical markers
      of bone turnover in postmenopausal women with an accelerated bone loss and
      osteopenia or osteoporosis. METHODS AND RESULTS: 72 women with significantly
      increased bone resorption were evaluated (urinary hydroxyproline/creatinine > or
      = 21.9 mmol/mol, mean age, 53.7 +/- 6.3 years, time since menopause 6.1 +/- 2.6
      years). All patients received daily 500 mg Ca2+ and 400 IU vitamin D supplement.
      48 patients with osteopenia and 24 patients with osteoporosis were randomly
      allocated to treatment with open-label 17 beta-estradiol (50 micrograms
      transdermally or 2 mg orally) or calcitonin (200 IU every other day). Bone mass
      was measured by dual-energy x-ray absorptiometry (DPX-L, Lunar, C.V., 1.10 +/-
      0.55% and 1.41 +/- 0.55%, lumbar spine and femoral neck, respectively) every six
      month for 2.5 year, bone stiffness was measured by ultrasound (Achilles, Lunar,
      C.V., 3.88 +/- 1.95%). Biochemical markers of bone turnover (plasma osteocalcin
      and tartrate-resistant acid phosphatase, serum bone specific alkaline phosphatase
      and urinary hydroxyproline) were measured before and after 6, 12 and 24 month of
      treatment. Patients who received 17 beta-estradiol experienced significant
      increases (p < 0.05) in bone mass on the first and second year (by 2.6% and 2.1%
      at lumbar spine, 1.1% and 1.0%, at femoral neck, and 2.3% and 2% at the heel). A
      significant positive correlation was found between rates of bone mass change in
      all sites (p < 0.001). No statistically significant bone changes were found in
      calcitonin treated patients. In 17 beta-estradiol treated patients, biochemical
      markers of bone turnover decreased by 40-50% to the mean values in premenopausal
      women. In calcitonin treated patients, biochemical markers reached the upper
      normal limit. CONCLUSIONS: Estrogen replacement therapy increases bone mass in
      lumbar spine as well as in femoral neck. It is efficient for both prevention and
      treatment of postmenopausal osteoporosis. Salmon calcitonin effectively prevents
      bone loss. Efficacy of both the treatment can be assessed after 6 months using a
      biochemical marker of bone resorption and after 2 years using dual-energy x-ray
      densitometry.

PMID- 9264869
TI  - [Thyroid, ovarian and adrenal antibodies in female patients with autoimmune
      thyroiditis].
AB  - BACKGROUND: In patients with autoimmune thyroiditis confirmed by clinical and
      laboratory tests frequently complaints associated with ovarian disorders are
      encountered. In order to verify the polyclonal activation of the autoimmune
      response of patients with autoimmune thyroid disease the authors investigated the
      presence of autoantibodies against the thyroid and adrenals. METHODS AND RESULTS:
      696 patients were selected (mean age 47.9 years) with autoimmune thyroiditis from
      a group of 1939 patients examined for the presence of antibodies against thyroid
      peroxidase (TPO). In these patients also the presence of antibodies against
      ovaries was assessed (in 183 women, i.e. 26.3%), the adrenals (zona glomerulosa
      in 136 women, i.e. 19.5%, zona fasciculata in 10 women, i.e. 1.4%, zona
      reticularis in 114 women, i.e. 16.4%) and the adrenal medulla in 46 women, i.e.
      6.6%. The basic group was divided into two sub-groups depending on the presence
      of ovarian antibodies. In the group of 183 women with positive antibodies against
      the ovaries and TPO positivity against the zona glomerulosa was found in 93
      women, i.e. 50.8%, the zona fasciculata in 7 women, i.e. 3.8%, the zona
      reticularis in 70 women, i.e. 38.3%, the adrenal medulla in 37% i.e. 20.2%. In
      the second group of 513 patients with positive TPO and negative antiovarian
      antibodies against the zona glomerulosa were found in 43 women, i.e. 8.4%, zona
      fasciculata in 3 women, i.e. 0.6%, zona reticularis in 44 women, i.e. 8.6% and
      against the adrenal medulla in 9 women, i.e. 1.8%. CONCLUSIONS: These results
      confirmed that in organ specific autoimmune thyroid disease also other
      autoantibodies against endocrine organs may be present, i.e. against the ovaries
      and adrenals. The relative frequency of a common finding of autoantibodies
      against organs which comprise steroid producing cells can be explained by the
      fact that for the ovaries and the adrenals a common antigen of steroid producing
      cells is typical.

PMID- 9264870
TI  - [Clinical spectrum of the antiphospholipid syndrome].
AB  - Antiphospholipid syndrome (APS) is characterized by multiple arterial and venous
      thromboses, repeated spontaneous abortions and thrombocytopenia, together with
      the presence of antiphospholipid antibodies in serum. We present three patients,
      two men and a woman, at the age of 43, 24 and 23 years respectively. The younger
      man and the woman had secondary APS and systemic lupus erythematosus, the older
      man had primary APS. The symptoms and course of the disease were different. The
      older man lives 17 years after the onset of first symptoms with multiple
      neurologic disorders, the younger man is symptomless. The woman died several
      months after the acute onset of the disease.

PMID- 9264871
TI  - [Recommendations for diagnosis and therapy of hyperlipoproteinemias in adulthood
      prepared by the Czech Atherosclerosis Society].

PMID- 9264872
TI  - [Professor L. Borovansky was born 100 years ago, 1 April 1987].

PMID- 9264873
TI  - [Natural toxic substances in food].
AB  - Foods, mainly those of plant origin and mushrooms, contain natural toxic
      substances. Their acute toxicity is as a rule mild, but carcinogenic and
      teratogenic effects cannot be ruled out. They include e.g. cyanogens,
      lathyrogens, hydrazines, glucosinolates and related goitrogens, cumarins,
      saponins, alkaloids and glycoalkaloids, biogenic amines, enzyme inhibitors, such
      as lectins (haemagglutinins) and trypsin inhibitors and chelating substance e.g.
      phytates and oxalates. These toxic substances are partly removed by technological
      processes. When principles of a varied diet are respected, the health risk is
      reduced to a minimum.

PMID- 9264874
TI  - [Therapy of affective disorders].
AB  - The article presents a brief review of therapies of the affective disorders. Two
      basic approaches are used: psychotherapeutic and biological, which comprises
      mainly pharmacotherapy and electroconvulsive therapy. The treatment may be
      divided into 3 stages as concerns the time course: acute treatment, continuation
      treatment, prophylactic treatment. Therapeutic strategies for depressive episode,
      recurrent depressive disorder, manic episode, bipolar affective disorder,
      dysthymia and cyclothymia are mentioned in the text.

PMID- 9264876
TI  - [Analysis of HLA class I molecules using isoelectric focusing. Its application in
      selection of bone marrow donors].
AB  - BACKGROUND: Differences between HLA proteins class I are assessed by serological
      typing using HLA allo-antisera. This method suffices for the assessment of HLA
      signs in allogenic transplantations of bone marrow in genotypically identical
      siblings. However, it does not suffice in the selection of donors from the wider
      family of a related or not related donor from the register of voluntary bone
      marrow donors. In order to assess the polymorphism of the HLA-class I not
      detected by serological typing other more sensitive techniques are introduced. In
      the authors department one-dimensional isoelectric focusing was introduced as an
      auxiliary method for evaluation of identity of molecules in HLA-class I between
      bone marrow recipient and donor. METHOD AND RESULTS: The authors introduced the
      method of one-dimensional isoelectric focusing which uses for detection of
      molecules of HLA-class I a polyclonal antibody against heavy chains of HLA
      molecules class I and a secondary antibody labelled by alkaline phosphatase.
      Forty-one pairs of bone marrow donors and recipient were examined. In six
      instances, i.e. in almost 15%, the authors detected by isoelectric focusing
      disagreement in HLA molecules class I. The authors present three interesting
      pairs of donors and recipients where isoelectric focusing helped with the
      selection of a suitable bone marrow donor. CONCLUSIONS: The isoelectric focusing
      is at present another method which helps to reveal differences in HLA class I
      molecules. When methods of DNA analysis are introduced to recognize alleles of
      the HLA-I class, correlation with serologically and biochemically assessed
      variants wil be an essential guide in the evaluation of the final typing of HLA
      molecules class I.

PMID- 9264875
TI  - [Late sequelae of comprehensive antineoplastic therapy in children and
      adolescents with solid extracranial tumors. Effect on growth, pubertal
      development and gonadal function].
AB  - BACKGROUND: Modern treatment of oncological diseases increases markedly the
      chance of long-term survival and permanent recovery. Due to frequently highly
      aggressive treatment it is however associated with the risk of late sequelae in
      the surviving patients. Comprehensive care of patients includes therefore not
      only control of the neoplastic disease but also efforts of maximal improvement of
      the quality of life of the patients. In young subjects, in view of their long
      term perspective, this problem is particularly important. METHODS AND RESULTS: In
      32 patients (25 boys and 7 girls) with extracranial solid tumours without primary
      endocrinological symptomatology (m. Hodgkin, neuroblastoma, ganglioneuroblastoma,
      nephroblastoma, Ewings sarcoma and others) a single examination was made
      assessing height, body weight, grade of sexual maturation according to Tanner, in
      boys testicular volume by means of a orchidometer and 20 other anthropometric
      dimensions. The mean age at the time of examination was 16.5 +/- 4.1 years, the
      mean age at the onset of treatment 6.1 +/- 4.8 years. The patients height, -0.4
      +/- 0.9 SD, differs from the Czech national standard (p = 0.025). Impaired growth
      was recorded in 12.5% patients and had heterogenous causes. The authors proved a
      negative effect of radiotherapy on the growth of the spine, most markedly in
      children subjected to irradiation of the abdomen and chest and a highly
      significant reduction of the testicular volume in boys after cytostatic treatment
      of m. Hodgkin. CONCLUSIONS: The results are consistent with studies made abroad
      and indicate the necessity of comprehensive long-term follow-up of somatic growth
      and development of the gonads in oncological child patients.

PMID- 9264877
TI  - [Mutation of the phenylalanine hydroxylase gene in the population of central
      Bohemia. Relation to the clinical picture of phenylketonuria].
AB  - BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive, disease,
      heterogeneous at the molecular level, caused by mutations in the gene of
      phenylalanine hydroxylase (PAH). The objective of the present work was to
      identify mutations and their frequency in the Central Bohemian and Prague
      population in relation to the clinical phenotype. METHODS AND RESULTS: The
      authors analyzed a group of 33 patients from 32 unrelated families. The
      phenotypic manifestations were classified as non-PKU hyperphenylalaninaemia (non
      PKU-HPA), mild and classical PKU. Sixty-six mutant alleles of the PAH gene were
      analyzed by means of the polymerase chain reaction on a Perkin Elmer (480)
      apparatus and on PHC Techne. A total of eight mutations linked with five
      haplotypes were detected. R408W mutation linked with 2.4 haplotype was detected
      on 53% of mutant alleles. No type of mutation was detected by hitherto published
      procedures in 27% of mutant alleles. CONCLUSIONS: The finding on the distribution
      and frequency of mutations indicate a genotypic homogeneity of the PKU population
      in the Central Bohemian area and Prague and are consistent with hitherto
      published data from the Czech Republic. The revealed data can be used in prenatal
      and postnatal DNA diagnosis and genotype classification of PKU.

PMID- 9264879
TI  - Gene of the month.

PMID- 9264878
TI  - [Treatment of meningococcal sepsis].
AB  - BACKGROUND: Incidence of meningococcal diseases and sepsis caused by a new
      invasive strain of Neisseria meningitidis group C: 2a: P 1,2 has been observed in
      the Czech republic within the last 3 years. In 1994 the highest incidence of this
      disease was in the West region. Ten of the most critically ill patients were
      treated at the Department of Anaesthesiology and Intensive Care. The aim of this
      work was to present principles of the treatment of this disease. METHODS AND
      RESULTS: In 1994 we treated 10 patients, 8 male and 2 female with average age of
      11 years (range from 5 months to 20 years). Causing strain identification was
      done in 9 patients, in one patient causing strain was not identified. All
      patients had typical clinical symptoms of the disease. All of them were treated
      according to the same protocol of the invasive complex treatment including
      artificial ventilation, circulation support, Ceftriaxon combined with potassium
      salt of benzylpenicillin, i.v. immunoglobulins, fresh frozen plasma, heparin,
      fibrinogen and antitrombin III. Average length of the stay in the Intensive Care
      Unit was 5 days (range from 1.5 hour to 10 days). Survival in our group was 70%.
      CONCLUSIONS: Early started complex therapy is a decisive factor of its success. A
      uniform protocol of treatment and its wide publication even to the first contact
      level can increase a chance for survival.

PMID- 9264880
TI  - Refolding with a piece of the ring.

PMID- 9264881
TI  - Crossing borders: nursing practice, teaching and research together into the 21st
      century.
AB  - This paper addresses a research project currently in progress. It is a postmodern
      ethnographic and (auto)biographical undertaking that simultaneously redraws the
      methodological and theoretical boundaries of conventional ethnographic work while
      it engages a 'praxis' oriented approach to working collaboratively and creatively
      with nurses from both clinical practice and academia. Only the broadest
      parameters of this 'project of possibility' are outlined--to do otherwise would
      be antithetical to its participatory, processual and provisional character. It is
      an unprecedented venture between those who think and write about the culture of
      clinical nursing and those who actually live it on a daily basis.

PMID- 9264882
TI  - The lifeworld of relatives of critically ill patients: a phenomenological
      hermeneutic study.
AB  - This paper describes a phenomenological hermeneutic study of the experiences of
      relatives of critically ill patients. The study was conducted at a large tertiary
      referral hospital in Sydney, Australia. The participants were 15 female family
      members of critically ill patients. Taped conversations between the researcher
      and participants were conducted and interpreted using a hermeneutic
      transformative process. Four themes were identified: 'being-with', 'seeing',
      'plain talk' and 'making sense'. The theme 'plain talk' was concerned with the
      importance of sensitive and timely communication, and was congruent with previous
      research findings. The other three themes, however, surfaced new understanding of
      the relative's experience. 'Making sense' focused on the participant's
      understanding of the experience of having a critically ill relative. 'Being with'
      was concerned with the desire of the participants to be with their loved one.
      'Seeing' highlighted the importance of actually seeing the patient.

PMID- 9264883
TI  - The practical implications of a critique of traditional science.
AB  - Patti Lather writes of the convincing critique of traditional science that has
      amassed in the past 2 decades. The displacement of the assumptions of traditional
      science makes space for some interesting and exciting developments in the human
      sciences. However this theoretical rearrangement is not matched in practical
      spheres. While Lather is referring to education research I would include nursing
      when she writes, '...positivism retains its hegemony over practice'. There is
      ample evidence of the effects of this domination in nursing. Nurses work closely
      with the medical profession, which is still predominantly influenced by
      'scientific' research, and health administrators who are in organizations which
      are bureaucratic and preoccupied with rationally. Medical practitioners control
      research ethics committees and funding bodies, which have relatively few nursing
      representatives and continue to judge proposals for qualitative projects by
      applying standard 'scientific' criteria. The administrators control budgetary
      matters and impose standards in the organizations. The dominance of traditional
      science needs to be challenged if nurses wish to make a place for different ways
      of knowing in their practice.

PMID- 9264884
TI  - Reflective midwifery practice: facilitating midwives' practice insights using a
      distance education reflective practitioner model.
AB  - A study was undertaken to evaluate a reflective practitioner model with midwives,
      who self-selected into the project when they were studying the Bachelor of Health
      Science (Nursing) unit NR278, Advanced Nursing Practice, Midwifery. The
      theoretical assumptions that influenced the research were those forwarded by
      Schon (1983) and Boud, Keogh and Walker (1985), who argued that practitioners are
      often unaware of the sophisticated knowledge they have regarding the intricacies
      of their practice, but that this personal knowledge can be make explicit through
      reflective processes. The aim of the study was to research the use of a distance
      education reflective practitioner process that encouraged midwives to examine
      their practice with a view to making changes where necessary. All the research
      objectives were met to some extent, although each experience of the research
      process was particular to the individual participant. Analysis consisted of:
      interpretation of the participant's insights into their individual experiences;
      the researcher's interpretations of participant's experiences; and collective
      themes arising out of the research. This paper concentrates mainly on the
      participant's insights into their individual experiences of practising midwifery,
      using a reflective practitioner model.

PMID- 9264885
TI  - Constructing nursing practice: country of origin, culture and competency.
AB  - This study explored the everyday experiences of a group of overseas qualified
      female nurses from non-English speaking backgrounds (NESB) entering the New South
      Wales health-care system. Migrant women from a variety of NESB participated by
      describing their experiences in the hospital environment as qualified nurses.
      Analysed data suggest that the experience of being a migrant woman has a profound
      effect on how these nurses construct nursing practice. National wealth and the
      dominant government ideologies operating in a nurse's country of qualification
      shape the practice of nurses. Nursing therefore is socially and culturally
      constructed, yet nurses seeking to practise in New South Wales (and other parts
      of Australia) are assessed against the Australian Nursing Council (Inc)
      competencies. Do these competencies support the current ideology of
      multiculturalism or do they reflect a monocultural view of the world? This paper
      raises questions concerning the use of competencies as an assessment tool for
      locally qualified and overseas qualified nurses.

PMID- 9264886
TI  - Time to care? Time for reflection.
AB  - This paper develops a single shared experience within a guided reflection to
      highlight the process of guiding learning through reflection. The shared
      experience is a mundane everyday experience concerned with the ward sister on an
      acute elderly ward responding to a relative's request. From the reflective
      practice perspective, the analysis of a single experience becomes a significant
      source of knowledge to inform others' practice. Reflective practitioners always
      interpret extant knowledge for its relevance to their practice. This process is
      helped by reflective accounts because they are subjective and contextualized
      accounts and therefore aid interpretation.

PMID- 9264887
TI  - Registered nurses' knowledge and compliance with regulations relating to the
      administration of ward recordable medications.
AB  - An anonymous questionnaire assessing nurses' knowledge, attitude and compliance
      with legally mandated regulations relating to the administration of ward
      recordable drugs was administered by mail to a random sample of nurses registered
      in New South Wales, Australia. Sixty-four per cent of subjects (n = 318)
      responded. Both self-reported and colleague-reported compliance rates were less
      than 50%. A highly significant relationship was evident between knowledge and
      attitude, knowledge and reported compliance; and attitude and reported
      compliance. Factors that may influence non-compliance are discussed and the
      legal, ethical and policy implications of the findings are briefly explored.

PMID- 9264888
TI  - Does routine gowning reduce nosocomial infection and mortality rates in a
      neonatal nursery? A Singapore experience.
AB  - A 1 year prospective study on routine gowning before entering a neonatal unit was
      conducted in a maternity hospital in Singapore. This study was done based on
      previous work by Donowitz, Haque and Chagla and Agbayani et al., as there have
      been no known studies done in Singapore. The aim of the study was to test the
      hypothesis that routine gowning before entering a neonatal nursery does not
      reduce nosocomial infection and mortality rate. A total of 212 neonates from the
      neonatal intensive care unit (NICU) and 1694 neonates from the neonatal special
      care unit (NSCU) were studied. Neonates admitted during the 1 year study were
      assigned to the gowning (control) and no routine gowning (trial) group on every
      alternate 2 months. The hospital infection control nurse provided data on
      nosocomial infection. The overall nosocomial infection rate in the NICU was 24%
      (25 of 104 admissions) during gowning periods compared to 16.6% (18 of 108
      admissions) when plastic aprons were not worn before entry. In the NSCU, the
      overall infection rate was 1.5% (12 of 800 admissions) during gowning periods
      compared to 2.1% (19 of 894 admissions) when no gown was worn before entry.
      Results of the study found no significant differences in the incidences of
      nosocomial infection and mortality in the neonates. The cost of gowns used during
      the no routine gowning periods was S$2012.8 compared to S$3708 used during the
      routine gowning procedure. The investigators recommend that routine gowning
      before entering a neonatal unit is not essential and cost effective for the
      purpose of reducing infection. Rather the focus should be on adequate handwashing
      by all hospital personnel and visitors before handling neonates.

PMID- 9264889
TI  - Innovations in dementia care.
AB  - Creating a homelike environment in an institutional setting that caters for
      dementia sufferers requires flexibility, understand and insight. A homelike
      environment frequently only addresses the physical appearance of the facility
      without over considering what was homelike for the resident prior to coming into
      care. The use of chemical and mechanical restraints to overcome adverse behaviour
      has been the accepted norm in many nursing homes without consideration being
      given to the diverse effects of these management tools. The use of the clinical
      type setting for routines and policies has been in place for many years, yet it
      is these very routines that have been found to cause the most distress to
      dementia sufferers. The challenge of change is the greatest reason for
      maintaining the status quo but change can bring its rewards with the improved
      quality of life experienced by those residents who lived in a nursing home. This
      paper describes a programme that addresses the advantages of changing the
      environment for dementia sufferers and demonstrates that an improved quality of
      life can be achieved by removing the need for chemical and mechanical restraints.

PMID- 9264890
TI  - Increasing dietary fibre for patients in an acute hospital ward.

PMID- 9264891
TI  - How much does your patient drink?

PMID- 9264892
TI  - Australia: remote area nurses' experiences of violence.

PMID- 9264893
TI  - Slovenia: development of primary health care nursing.

PMID- 9264894
TI  - United States of America: primary nursing revitalized.

PMID- 9264895
TI  - Myanmar: perceptions of the community towards changes in nursing education.

PMID- 9264896
TI  - Nursing-managed beds in the United Kingdom.

PMID- 9264897
TI  - Proceedings of the International Conference on Combinatorial Library Methods for
      Basic Research and Drug Discovery. Tucson, Arizona, December 2-4, 1995.

PMID- 9264898
TI  - Late intrauterine cytomegalovirus (CMV) infection: clinical and neuroimaging
      findings.

PMID- 9264899
TI  - [Changes in cerebral vasomotor reactivity in relation to respiratory and
      metabolic stimuli: an analysis of its behavior in hypertensive and normotensive
      subjects].
AB  - We know that increases in the arterial blood pressure determines changes in the
      behaviour of the cerebrovascular resistance and also the possible lack of
      vasomotor reactivity. In order to clarify the pathway of circulatory vasomotor
      reactivity in arterial hypertension, we carried out a study on a group of
      hypertensive subjects (20 patients) who were compared to a group of normotensive
      controls (18 patients). A transcranial doppler (TCD) study was performed with
      rebreathing tests (apnea and hyperventilation) and it was carried out in both
      groups of subjects. The TCD was repeated after an administration of sublingual
      pill of nitroglycerin. In both groups the hyperventilation caused a significant
      reduction in the velocity peak in the middle cerebral artery (norm.: 84.88 +/-
      4.86 cm/sec 60 +/- 5.2 cm/sec; hyperten. 84.50 +/- 7.1 cm/sec 58.80 +/- 5.47
      cm/sec) in contrast apnea induced a major increase in the velocities (norm.:
      84.88 +/- 4.86 cm/sec 102.50 +/- 4.89 cm/sec; hyperten.: 84.50 +/- 7.1 cm/sec
      101.59 +/- 10.6 cm/sec). We noticed a statistical significant difference between
      the velocities recorded in the different tests (Anova test p < 0.0001). The
      behaviour of the velocities in the rebreathing tests after nitroglycerin was
      similar when compared to the same test were performed without the drug. This
      study suggests that there is no difference in the behaviour of the cerebral
      reactivity between normotensives and the hypertensive subjects without vascular
      or cardiac compliance. Finally we would emphasize the role of TCD in the
      recording changes of cerebrovascular resistances due to pressure or metabolic
      causes.

PMID- 9264900
TI  - [The therapy of arterial hypertension: a comparison between ACE inhibitors and
      angiotensin-II-receptor antagonists].
AB  - The efficaciousness of ACE inhibitors in arterial blood hypertension is well
      known. These drugs decreased the incidence of hypertension and myocardial
      infarction in population. However, they increase tissue levels of some kinines,
      that may be responsible of some adverse reactions (cough, etc.). Angiotensin
      receptor antagonists can minimize the adverse reactions due to kinine
      accumulation and may increase the safety of the antihypertensive drug-treatment.
      Pharmacological and clinical aspects of angiotensin-receptor antagonists are
      discussed.

PMID- 9264901
TI  - [Exfoliative conjunctival cytology in Sjogren's syndrome].
AB  - The study has been performed in order to give a contribution to the knowledge of
      the conjunctival cytology in Sjogren's syndrome. Exfoliated cells were obtained
      by a tampon from the inferior conjunctival sac of 11 patients affected by primary
      or secondary Sjogren's syndrome; the material was placed onto a microscope slide
      and it was stained with May-Grumwald-Giemsa, after the ferning test had been
      performed. Tear production had been previously assessed in all patients by
      Schirmer's I test and basic secretion test that showed an evident tear fluid
      hyposecretion. Cytoanalysis of tear fluid showed, in all patients, a marked
      lymphocytosis, presence of epithelial cells (sometimes cell-adhesion) and a
      number of "snake-cells", with a nucleus-cytoplasm ratio in favour of cytoplasm.
      Some of those cells have a thicker cytoplasmic membrane and/or a spindle-shaped
      peripheral nucleus, characteristic finding of keratoconjunctivitis sicca. In all
      cases we found mucus and fibrin (sometimes with included cells), organic debris
      and big crystals, some of which aggregated.

PMID- 9264902
TI  - [Celiac disease today].
AB  - Recent studies have been reported for coeliac disease a new prevalence: 1:200 in
      Europe, 1:184 in Italy. These improvements have been possible for new diagnostic
      methods and techniques available today: antigliadin, antireticulin and
      antiendomysium antibodies. These serologic markers have been detected, in recent
      advances, new clinical presentations for coeliac disease: not only typical
      gastrointestinal symptoms (diarrhea, recurrent abdominal pain, etc), but many
      atypical symptoms have been described: sideropenic anemia, short stature, growth
      retardation, dermatitis herpetiformis, small alterations, alopecia, etc. New
      groups of patients have been also identified: some patients, clinically
      asymptomatic, with positive serology and a small intestinal biopsy suggestive for
      coeliac disease; they have shown histopathologic improvement with gluten free
      diet ("silent" coeliac disease). Another interesting group consists of
      asymptomatic patients with a positive serology for AGA and AEA antibodies, but
      normal gastrointestinal biopsy with free diet; they develop later in life,
      mucosal atrophy and normalization after gluten free diet ("latent" coeliac
      disease). It must be emphasized that classes of antibodies (in association with
      peroneal biopsy) have been identified in the last years, new clinical
      presentations of coeliac disease and new associations with other autoimmune
      pathologies.

PMID- 9264903
TI  - [Vasodilation in cirrhosis: is CGRP (calcitonin gene-related peptide) also among
      the possible mediators?].
AB  - According to cirrhotic patient's hyperkinetic circulatory state and to different
      pathophysiologic moments of kidney and liver failure, it is suggested that in
      cirrhosis a vasoactive balance is changed to more active vasodilatation. Also
      calcitonin gene-related peptide (CGRP) is likely involved in this change.

PMID- 9264904
TI  - [Imaging diagnosis in the study of pulmonary and extrapulmonary tuberculosis].

PMID- 9264905
TI  - [A case of severe thrombocytopenia in infectious mononucleosis].
AB  - The authors discuss a case of thrombocytopenia with bleeding occurred in a young
      woman with infectious mononucleosis admitted to the Infectious Disease Department
      of University of Catania. It is reported the pathogenetic hypothesis of virus
      induced thrombocytopenia and therapy.

PMID- 9264906
TI  - [The ethnopharmacology of hallucinogens: from "primitive rites" to their
      "presence" on TV. Proposals for the year 2000].
AB  - Hallucinogens are the chemicals which in nontoxic doses produce changes in
      perception, mental confusion, memory loss, or disorientation for person, place
      and time, with organic brain reactions. Mescaline and LSD are historically the
      most interesting hallucinogens. Today the cannabis is very important, socially.
      Traditional hallucinogens survive everywhere in the world. A dramatic increase in
      use of cartoons in drug education and prevention programs prove great damages: in
      comics and films often have stimulated the appetite for drug experimentation
      (seduction of innocent, R. K. Siegel). Cartoons and comics are instruments for
      correcting perceptions and behaviour of youth and youthful drug abusers. As the
      hallucinogens.

PMID- 9264907
TI  - [The usefulness of plasmapheresis in a case of nephrotic syndrome in Berger's
      disease].
AB  - Berger's disease, or IgA mesangial nephropathy, is a frequent form of focal
      and/or segmental proliferative glomerulonephritis that occasionally may present
      as nephrotic syndrome. The authors reports a clinical case of a young woman come
      to their observation with a severe clinical picture characterized by asthenia,
      anasarca, serious no selective proteinuria, microscopic hematuria, blood
      hypotension from mesangial proliferative glomerulonephritis IgA. Because of the
      null response to traditional therapy the patient was submitted to plasmapheresis
      "cascade model", or double filtration, a certainly experimental treatment for
      this disease, and a remission of the nephrotic syndrome was obtained as confirmed
      by follow-up at three, six months and one year. Since at present times the
      therapy is supportive only and no therapeutic maneuvers have been found to be
      consistently effective in the Berger's disease, plasma exchange plus
      immunodepressive therapy seems to be useful particularly in the rare patients
      with rapidly progressive glomerulonephritis. Further and more extensive studies
      and a fair follow-up are necessary to prove our results.

PMID- 9264908
TI  - [Adrenal myelolipomas: their magnetic resonance assessment].
AB  - Adrenal myelolipomas are rare nonfunctioning neoplasias consisting of a variable
      mixture of mature fat and bone marrow tissue. In the present study MRI
      appearances of six adrenal myelolipomas are presented. MR exams of six patients
      in which a conclusive diagnosis of adrenal myelolipomas was reached by means of
      surgery (1 case), US-guided fine-needle biopsy (3 cases) and typical diagnostic
      imaging in association with stability on US follow-up for at least two years (2
      cases) were retrospectively evaluated. MR sequences protocol included pre- and
      post-contrast (Gd-DTPA) SE T1-weighted images and SE proton density and T2
      weighted images. Five adrenal masses were examined by means of combination of
      gadolinium administration with a SE T1-weighted modified three-point Dixon
      technique. Three different MR structural patterns were pointed out: a)
      homogeneous hyperintense masses on T1-weighted images with intermediate signal on
      T2-weighted images, suggestive for predominantly fat-containing lesions (2
      cases); b) heterogeneous masses with fat intensity areas and hyperintense areas
      on T2-weighted images and on post-contrast T1-weighted images, suitable for mixed
      fatty and myeloid elements (2 cases); c) nodules hypointense to the liver on T1
      weighted images and hyperintense on T2-weighted images and after gadolinium
      administration, suggesting tumors primarily composed of myeloid cells (2 cases).
      A precise determination of fatty and myeloid elements within the lesions was
      observed by means of "water" and "fat" images provided by modified three-point
      Dixon technique. In conclusion, MRI allows to determine the various structural
      components of myelolipomas and therefore appears to be a very reliable technique
      in the diagnosis and characterization of the different structural patterns of
      this rare adrenal pathology.

PMID- 9264909
TI  - [Transcranial ultrasonography in neurosurgery].
AB  - Transcranial doppler sonography is a diagnostic tool that allows the noninvasive
      study of intracranial circulation. In patients with aneurysmal subarachnoid
      hemorrhage, cerebral vasospasm is promptly diagnosed, even before clinical
      related symptoms. Feeding arteries of an arteriovenous cerebral malformation can
      be detected and their variations can be correlated to the treatment
      (neurosurgical and/or neuroradiological). When raised intracranial pressure
      (namely in head trauma), transcranial doppler sonography depicts vasospasm and/or
      typical variations of the waveforms, suggesting intracranial circulatory arrest.

PMID- 9264910
TI  - [The effect of formoterol on light or moderate bronchial asthma due to allergy to
      Parietaria officinalis].
AB  - We have evaluated the effect of formoterol in 28 patients (20 males and 8
      females, mean age 25.4 years) affected by mild or moderate bronchial asthma due
      to Parietaria allergy. Inhaled formoterol was given at the dosage of 24 mg twice
      a day for 10 weeks during the pollen season. Patients had to record daily the
      peak respiratory flow, the severity and the number of asthmatic attacks and the
      severity of cough. Moreover they had to report the use of additional
      bronchodilators and the possible side effects. The treatment with formoterol
      obtained in increase of PEF values from 254 +/- 6.1 to 329 +/- 6.1 l/min in the
      morning and from 237 +/- 7.1 to 365 +/- 7.1 l/min in the evening. A significant
      improvement on the number of asthmatic attacks and on the cough was also
      obtained. No side effects have been reported. Our results show the safety and the
      efficacy of formoterol in the treatment of mild or moderate bronchial asthma.

PMID- 9264912
TI  - [Intrahepatic cholestasis].
AB  - The intrahepatic cholestasis is not an common syndrome, in particular way in
      people between 50 and 60 years of age. It is often unknown or confused, because
      of itching, with allergic or dermatologic diseases. The most frequent causes of
      intrahepatic cholestasis are primary sclerosing cholestasis, primary biliary
      cirrhosis and hepatic cirrhosis. The pathogenetic mechanism is the faulty
      secretion of bile and, more bile salts. The diagnosis is allowed by anamnesis,
      objective examination and, above all, biochemical markers of cholestasis,
      echography, TC, NMR and liver biopsy. Therapy consist of generic (hypolipidic
      diet, liposoluble vitamin and others) and specific (UDCA, SAMe) measures.

PMID- 9264911
TI  - [The evaluation of the use of DEAE-dextran in glycemic control in diabetic
      patients in pregnancy].
AB  - Thirty pregnant women with a pre-gestational history of type II diabetes or sugar
      intolerance and recruited during the second trimester of pregnancy, were
      administered DEAE-dextran (1 g x 3 times a day) in association with compensatory
      insulin therapy. Results of the end of trial tests showed amelioration of all of
      the parameters studied. The sugar curve after 120' from glucose load (100 g at
      fasting), showed a highly significant decrease at T90. Triglycerides T0 vs T90
      gave p = 0.0001, probably due to improved body utilization of the insulin. DEAE
      dextran was well tolerated and all of the patients enrolled at the beginning,
      completed the trial.

PMID- 9264913
TI  - [Gastric neoplasms: their characterization, assessment of the degree of parietal
      infiltration and check on recurrence. The potentials and limits of CT, endoscopic
      US and MR].
AB  - In this report we reviewed the role of CT, of endoscopic ultrasonography and of
      MR in the study of the gastric wall, to assess the degree of parietal
      infiltration to characterize gastric neoplasms. Finally we assess the CT role to
      check gastric carcinoma recurrences.

PMID- 9264914
TI  - [Is the placebo still ethically acceptable and scientifically useful in clinical
      drug experimentation?].
AB  - Here, the authors address the question whether the administration of placebo, in
      clinical trials of drugs to be registered or already registered, is ethically
      acceptable and/or scientifically useful. An important issue, particularly in view
      of the different opinions emerging in the international scientific community.
      Since many diseases are already treatable with established therapies and drugs,
      clinical trials should be performed mainly with placebo containing the
      appropriate active compound, in agreement with the Helsinki declaration. Active
      placebo should be employed when slightly modified compounds are tested and when
      trials are in phase 2/b, 3 or 4. The use of active placebo in these settings
      would be more correct from a scientific, ethical and economical point of view.

PMID- 9264915
TI  - [Respiratory rehabilitation of the elderly patient: results and prospects].
AB  - The epidemiology and the principal indications of the pulmonary rehabilitation
      are firstly summarized, along with its peculiar aspects in the aged people. Then
      the outcomes of some significant studies are described, taking into consideration
      three areas of objectives aimed by the authors: improving quality of life,
      increasing survival, and assessing some physiological parameters. Finally, a few
      guidelines in the field of the pulmonary rehabilitation research are highlighted
      particularly emphasizing the singly-used therapeutic techniques and the control
      group.

PMID- 9264916
TI  - Special issue on the nucleolus, dedicated to Asen Hadjiolov.

PMID- 9264917
TI  - [New strategies for the development of tolerance following organ
      transplantation].

PMID- 9264919
TI  - [The effect of short-term hyperventilation on the concentration of ionized serum
      calcium].
AB  - BACKGROUND AND OBJECTIVE: Paraesthesias and carpopedal spasms on hyperventilation
      are explained by a reduction in ionised serum calcium (ISC). We tested whether 5
      minute hyperventilation changes the concentration of ISC. SUBJECTS AND METHOD:
      Arterial blood samples were obtained via a small plastic catheter introduced into
      the femoral artery of ten healthy male volunteers (mean age 33 years) before,
      during and after 5 minutes of hyperventilation, which was achieved by deep and
      rapid breathing and considered adequate when the end-expiratory pCO2 had fallen
      to 2.5 kPA within the first minute and remained below this level during the
      remaining 4 minutes. These criteria were met in nine of the ten patients. The ISC
      concentration was measured with an ion-selective electrode, the pH, paCO2 and
      bicarbonate levels with an autoanalyser. RESULTS: Paraesthesias of the fingers
      and hand occurred in nine of the volunteers, carpopedal spasms in seven. Despite
      a definite rise in pH from 7.39 +/- 0.02 to 7.75 +/- 0.045, the concentration of
      ISC did not change significantly during the hyperventilation. CONCLUSION:
      Paraesthesias and carpopedal spasms which occur during hyperventilation are not
      caused by a fall in ionised serum calcium in arterial blood.

PMID- 9264918
TI  - [The long-term therapy of hypothalamic-hypophyseal Cushing's syndrome with
      mitotane (o,p'-DDD)].
AB  - BACKGROUND AND OBJECTIVE: Drug treatment of hypothalamic-pituitary Cushing's
      syndrome is indicated if standard surgical intervention is not possible or has
      failed. The question arises whether, after unsatisfactory treatment with various
      adrenostatic drugs, mitotane (o,p'-DDD), used against adrenal cortical cancer, is
      efficacious and free of significant side effects when used long-term. PATIENTS
      AND METHODS: The results of long-term administration of mitotane to six patients,
      including one pregnant woman, were analysed retrospectively. After a moderate
      initial dosage of 3.0 g daily a maintenance dose of minimally 0.5 g per week was
      given or the treatment temporarily interrupted. The concentration of urinary free
      cortisol served as the main criterion of efficaciousness, together with the
      clinical course. The plasma concentrations of cortisol, aldosterone and ACTH were
      also determined, as well as routine clinicochemical parameters. RESULTS: Cortisol
      excretion became normal in all patients between the 2nd and 10th treatment month,
      falling from 919 +/- 621.3 nmol daily in the six months before treatment to 162
      +/- 93.0 nmol daily in the third six-month treatment period (mean +/- standard
      deviation). Normal cortisol excretion and regression of symptoms was noted, dose
      dependent, as long as the 12th year after start of treatment. Adrenocortical
      insufficiency occurred in one patient and at times required hormone substitution,
      followed by lasting remission without special treatment. Significant side effects
      were not observed other than a reversible increase in gamma-glutamyl
      transpeptidase. CONCLUSION: Mitotane proved to be an efficacious drug which in
      exceptional cases can be used without significant side effects in low dosage for
      the long-term treatment of hypothalamic-pituitary Cushing disease.

PMID- 9264920
TI  - [Visceral leishmaniasis with an unusually long incubation time].
AB  - HISTORY: A 25-year-old woman of Yugoslavian origin came to Germany two years
      before and did not leave Germany since this time. She developed a
      phlebothrombosis during pregnancy which was treated surgically and with
      subsequent heparinisation. The pregnancy had to be terminated by section because
      of abnormal liver functions and increased blood pressure. These values returned
      to normal within two months. Further tests again showed raised liver function
      tests (GOT 57 U/l, GPT 71 U/l) and antibodies against smooth muscle and actin.
      Autoimmune hepatitis was diagnosed and prednisolone given (100 mg daily). In the
      subsequent 4 months the patient progressively lost more weight and a pancytopenia
      developed. Suspected of having a systemic haematological syndrome she was
      admitted to hospital. FINDINGS: Physical examination was unremarkable except for
      hepato- and splenomegaly (spleen 15.6 cm in diameter by sonography). Laboratory
      tests showed hypergammaglobulinaemia (50 g/l, 53%), increased WBC count, as well
      as decreased haemoglobin concentration and platelet count (900 WBC/microliter, Hb
      10.9 g/l, 146,000 platelets/microliter). Bone marrow puncture unexpectedly
      revealed a large number of Leishmania donovani. TREATMENT AND COURSE: Five-valent
      antimony was administered (sodium stibogluconate 20 mg/kg daily intravenously as
      bolus for 14 days). She has been free of symptoms since then (follow-up period of
      one year). CONCLUSION: Visceral leishmaniasis is a rare disease in Europe.
      Incubation periods of several years have been reported and the infection can be
      easily mistaken for other chronic liver disease, in this case for an autoimmune
      hepatitis. Leishmaniasis should be included in the differential diagnosis of
      unclear liver disease if there is a suggestive history (country of origin or
      journey into an endemic area).

PMID- 9264921
TI  - [The diagnosis of gastritis].

PMID- 9264922
TI  - [Carcinoids of the gastrointestinal tract].

PMID- 9264923
TI  - [The breast cancer risk in postmenopausal estrogen substitution. The dilemma of
      risk assessment].

PMID- 9264924
TI  - [Consent in medical research and its retraction].

PMID- 9264925
TI  - [The radiation sensitivity of desmoid tumors].

PMID- 9264926
TI  - [Mycobacterium marinum as the rare cause of a chronic skin and soft-tissue
      infection].

PMID- 9264927
TI  - [Prospective study of attempted suicide].
AB  - The present study involves a prospective review of all patients who visited the
      Emergency Psychiatric Service during the period from December, 6, 1993 to June,
      5, 1994. A questionnaire was proposed to 1073 subjects (57.2% females; 42.8%
      males; mean age = 36.6 +/- 0.89). Demographic data, familial and personal
      characteristics, previous contacts with professional health services, and
      diagnosis (DSM III-R criteria) were collected. 52% of them were self-attempters,
      significatively younger (mean age 34.03 +/- 1.14) and more frequently females
      (61.5%). The parasuicides were more frequent in their families and in their
      personal past history. The previous contacts with health services
      (hospitalizations, consultations) were more frequent among patients who were
      admitted for psychological and/or psychiatric problems. 54% of self-attempters
      were repeating suicidal patients. There were more depressive disorders,
      parasuicides and drug/alcohol abuse in their families. A logistic regression
      analysis (stepwise) revealed the role of these factors in the repetition of
      parasuicides. This data supports the significance of a better knowledge of the
      potential significant factors for parasuicide. Preventive measures are necessary.

PMID- 9264928
TI  - [Antiphospholipid syndrome and psychosis].
AB  - The authors studies literature on both psychiatrics manifestations in several
      auto-immune diseases like systemic lupus erythematosus and the antiphospholipid
      syndrome, and the impairment of immune functions in psychiatrics diseases. They
      try to expose the relevance of collaboration between Medical practitioners and
      psychiatrists to study the immunogenetic hypothesis of psychotic diseases.

PMID- 9264929
TI  - [Deficit in selective attention and its evolution in depression].
AB  - Selective attention was measured in 34 depressed patients and 34 controls using a
      computerized version of the Stroop test, that included a manipulation of the
      stimulus onset asynchrony (SCA) in order to explore the efficacy of cognitive
      inhibition as a function of depression and of clinical amelioration of degression
      after therapy. Clinical tests included a measure of psychomotor slowing [Echelle
      de Ralentissement de Widlocher (ERD), the Hamilton (Psychiatric Rating Scale for
      Depression (HAMD), and the Brief Psychiatric Rating Scale (BPRS)]. Selective
      attention was measured with the Stroop test, which includes four measures: Word,
      Color, Color-Word, and Color-Word minus Color, or interference. All of these
      measures were deficient in the depressed patients, particularly Stroop
      interference. Even when additional time was given to inhibit the Stroop
      distractor in the SOA condition, depressed subjects still showed significantly
      inferior performance. After four weeks of anti-depressive treatment, fifteen of
      the patients were retested, and showed significant improvement on all the Stroop
      measures, particularly on Stroop interference. The improvement in performance on
      the attentional measures was comparable in magnitude to that seen on the clinical
      scales, and suggests that the interference measure can be a sensitive indicator
      of clinical status in depressed patients.

PMID- 9264930
TI  - [Attention models in evaluating schizophrenia].
AB  - Models of information processing, a part of cognitive psychology, have influenced
      theories of schizophrenia in the past few years. Study of attention disorders is
      an original approach of schizophrenics' cognitive disturbances. The authors have
      reviewed the literature of attention disorders in schizophrenia. Disorders of
      attention are analysed in different points of view. 'Subtype, syndromic (positive
      and negative forms) and symptomatic levels of analysis are documented. Subtype
      approach of attention disorders is not confirmed in the literature. Symptomatic
      approach of attention disorders in schizophrenia is actually well documented
      (especially for hallucination and delusion), but very heterogenous. Attention
      disorders are different in positive and negative syndromes of schizophrenia.
      Positive patients are more distractible and an early disorder of information
      processing is a part of cognitive disturbances of negative patients. Some
      neurobiological and information processing disturbances are discussed in
      reference of this syndromic approach.

PMID- 9264931
TI  - [Quantitative psychopathology of affect and emotion. Review of evaluation scales
      and emotion induction methods].
AB  - Emotions, affects and humor play an important part in psychopathology. This study
      describes the definition of these different terms as well as their psychological
      concepts. Concerning quantitative psychopathology, the available scales of
      evaluation of affects or emotions are destinated to evaluate the subjective
      compound of the emotions, depressive humor, seek for sensations, pleasure or
      anhedonia. They all have the same aim: the evaluation, in a subjective way, of
      the basic affectionate state of the subject at a precise moment in his life. The
      subject's affectionate reactivity to external emotional stimulations can also be
      studied using different methods of emotional inductions. These methods can be
      applied in a psychopathological as well as in a pharmacological point of view.

PMID- 9264932
TI  - [Chronic prenatal exposure to diazepam, brain metabolism and behavior: long-term
      consequences in the adult rat].
AB  - The long-term consequences of a neonatal exposure to diazepam (DZP) on behavioral
      abilities and local cerebral metabolic rates for glucose (LCMRglc) in selected
      brain regions involved in the control of memory and anxiety were studied in adult
      rats. Rat pups received a daily subcutaneous injection of 10 mg/kg DZP or of the
      dissolution vehicle from postnatal day (P) 2 to 21. Learning and memory were
      tested in P60-P70 rats on 5 consecutive days in a T maze and an eight arm maze
      while anxiety and reaction to novelty were tested in a 2 compartment box with a 2
      step staircase on one side. Social behavior was evaluated in a condition of
      restricted access to food. LCMRglcs were measured at P60 by the quantitative
      autoradiographic [14C]deoxyglucose method. In the T maze, when performed without
      delay between the 2 trials, the rate of alternation was significantly lower in
      DZP than in vehicle-exposed rats on the first 2 days of testing and similar in
      both groups on days 3-5. In the procedure with a 30 s intertrial delay, the rate
      of alternation was similar in DZP and vehicle-treated rats on all days of
      testing. In the eight arm maze, DZP-treated rats were more active, i.e. entering
      more arms per min than control animals. The number of arms entered before the
      first error was lower on day 1 and higher on day 3 in DZP compared to vehicle
      exposed rats. In the 2 compartment box, DZP-treated rats crossed more often the
      lower step of the staircase and spent more time than controls on the 2 steps of
      the staircase while control rats made more rearings than DZP-exposed rats in the
      well protected corner of the box. LCMRglcs were decreased by early DZP exposure
      in several cortical regions, mammillary body, septum and dorsomedian caudate
      nucleus. In conclusion, an early chronic DZP treatment induces an increase in
      activity, only a delay but no impairment in learning and leads to a decrease in
      the level of anxiety and emotionality leading to an active response to novelty.
      These quite subtle behavioral changes are accompanied by discrete metabolic
      changes and probably reflect the state of hyperactivity/hyperarousal of these
      animals which could result from a change in the distribution, the sensitivity
      and/or function of GABA-BZD receptors.

PMID- 9264933
TI  - [Acquired aphasia in a child with epilepsy (Landau-Kleffner syndrome). Comments
      apropos of a case with 1-year follow-up].
AB  - Authors report a case of Landau-Kleffner syndrome in a 6 year old boy. Landau
      Kleffner syndrome is a rare disorder characterized by the combination of acquired
      aphasia and epileptic abnormalities like diffuse spikes-and-waves in sleep EEG.
      Seizures are associated in 50 to 80% of cases and generally disappear at puberty.
      Behavior disorder ranges from minor psychomotor disturbances to psychotic-like
      features. Onset appears at an age between 3 to 7 years. The relationship between
      aphasia and epilepsy remains unclear, even if language improvement frequently
      follows EEG improvement. The hypothesis of an underlying encephalitis could
      explain the whole syndrome but is not yet validated. Therapy should associate
      antiepileptic drugs, corticosteroid treatment and speech therapy, but no
      controlled study is available to confirm this protocol. Aphasia recovery is
      generally incomplete. The evolution of behavior disorder is not well documented.
      In the reported case, one year after onset, sleep EEG again became normal,
      behavior disturbances had disappeared, but spoken language was still absent.

PMID- 9264934
TI  - [Indications for new antidepressants with reference to ICD-10: a waggish question
      or the future of psychiatry?].
AB  - The biological psychiatry's postulate is that depression is related to a lack of
      balance between the dopaminergic, noradrenergic and serotonergic monoaminergic
      neurotransmitters systems. These systems are related to cortico-striatal-thalamo
      cortical circuits, involving the association and limbic prefrontal cortex and the
      basal ganglia (caudate nucleus, putamen, nucleus accumbens, globus pallidus). The
      pharmacology of depression recently grows rich from "new" antidepressive agents,
      having selective monoaminergic activity: Selective Serotonin presynaptic Reuptake
      Inhibition ("SSRIs"), selective Reversible Inhibition of the Monoamine oxidase A
      ("RIMAs"), selective dopaminergic or noradrenergic agents. The last International
      Classification of mental and behavioural Disorders proposed by the World Health
      Organisation: the ICD-10, proposes a "new" classification of the depressive
      disorders based on atheoric "practical" diagnostic criteria. These criteria are
      unrelated to neurobiochemical, neuroanatomical or neurophysiological data.
      Reviewing the diagnostic criteria of depressive disorders proposed by the ICD-10
      in relation to the neuroanatomic structures subtending the monoaminergic theory
      of the depressions, the author attempts to answer to the question: is the "new"
      pharmacology of the depressions that constitute the "new" antidepressants blind
      or correlable to the "new" nosology of the depressive disorders proposed by the
      ICD-10? Finally, indications in first intention of the "new" antidepressive
      agents for each depressive disorder defined by the ICD-10 are proposed.

PMID- 9264935
TI  - [Development and contribution to the validation of a brief French version of the
      Yesavage Geriatric Depression Scale].
AB  - Depression in old age is underdiagnosed. In order to help detection, Yesavage et
      al. (1983) developed the Geriatric Depression Scale in a 30 items original
      version, with good reliability and validity. To abbreviate duration of
      examination, a shortened 15 items version was proposed (Sheikh et al., 1986) and
      a 4 items GDS for primary care attenders was also developed (D'Ath et al., 1994)
      with satisfactory metrological characteristics. The aim of this study is to
      develop a short French version and to contribute to its validation. French
      elderly depressives (181) and controls (66) were asked to complete the 30 items
      GDS (french version) and an other french self-rating scale, the QD2A (Pichot,
      1986). In an attempt to devise the short scale, data were subjected to logistic
      regression analysis, multiple regression analysis, item-total Spearman's rank
      correlation coefficients and finally to mean choice ranks combination method. The
      generated 4 items version (mini-GDS) was found to be highly correlated with GDS
      30 (r = 0.84, p < 0.0001) and with QD2A (r = 0.64, p < 0.0001) and had a high
      level of internal consistency (KR20 = 0.66). The sensitivity and specificity of
      the GDS 4 were 69% and 80% (cut-off 0/1) and against QD2A were 75% and 75% (cut
      off 0/1). Out of the four items, two were common with the D'Ath's 4 items
      version. Method with its different statistical developments was discussed and the
      4 selected items of the mini-GDS were compared with data from several authors who
      evaluated, discussed or examined factor structures of the 30 items GDS.
      Conclusion is that mini-GDS is reliable to easily detect a depressive
      symptomatology in the elderly, in different circumstances.

PMID- 9264936
TI  - Stress echocardiography: a well-established diagnostic tool. Proceedings of a
      symposium. Wuppertal, Germany, 5-6 June 1996.

PMID- 9264937
TI  - [An analysis of the dominant properties of the defensive conditioned reflex].

PMID- 9264938
TI  - [The limits of human physiological adaptation to the consequences of modern
      disasters].

PMID- 9264939
TI  - [The effect of experimental and high-altitude hypoxia on the bioelectrical
      processes of different brain structures and intercentral relations].

PMID- 9264941
TI  - [A cross-modal study of the perception of stimulus intensity in peripheral
      neurosensory hearing loss].

PMID- 9264940
TI  - [The age-related characteristics of the cerebral organization of verbal activity:
      an electrophysiological analysis].

PMID- 9264942
TI  - [Interhemispheric asymmetry and neuroimmune modulation in normal aging and
      Alzheimer's-type dementias].

PMID- 9264944
TI  - [The synchronization of human circadian rhythm with social timers: the role of
      motivation. II. The rhythms of autonomic functions].

PMID- 9264943
TI  - [The use of Kohonen's neuronal network for the analysis of the
      psychophysiological characteristics of persons with seasonal affective disorder].

PMID- 9264945
TI  - [The circadian variability of the rhythm of cardiac activity in healthy
      schoolchildren].

PMID- 9264946
TI  - [The characteristics of the shape and rhythmic structure of the pulse signal of
      the radial artery in arterial hypertension in childhood and adolescence].

PMID- 9264947
TI  - [The effect of increasing and decreasing physical loading on the breathing
      changes under additional resistance].

PMID- 9264948
TI  - [Ultrasonic evaluation of the isovolumic relaxation time of the human fetal
      heart].

PMID- 9264949
TI  - [The spatial organization of cortical electrical activity during the formation of
      cognitive set].

PMID- 9264950
TI  - [Individual reactions of the cardiovascular system in response to physical
      actions].

PMID- 9264952
TI  - [The circadian dynamics of body temperature and of the cardiorespiratory system
      of the human body during non-competitive yachting].

PMID- 9264951
TI  - [Correlational adaptometry as a method for evaluating cardiovascular and
      respiratory interaction].

PMID- 9264953
TI  - [The circadian dynamics of ergo- and trophotropic metabolism in subjects with
      different resistances to noise].

PMID- 9264954
TI  - [The effect of the duration of the stay in the north on the blood serum lipid
      profile during the polar night].

PMID- 9264955
TI  - [The characteristics of the course and outcome of pregnancy in women with anemia
      and a background of zinc deficiency].

PMID- 9264956
TI  - [The characteristics of the thrombocyte aggregation activity in the whole blood
      of newborn infants in relation to their degree of maturity].

PMID- 9264957
TI  - [The beta-adrenomimetic effect of human and animal blood serum].

PMID- 9264958
TI  - [Changes in the electrolyte content of human saliva, urine and sweat under
      repeated heat exposures].

PMID- 9264959
TI  - [The promotional dissertation of Joseph von Quarin as a mirror of the status of
      medical entomology in the middle of the 18th century].
AB  - Joseph von Quarin (1733-1814), court physician to the Emperor of Austria at the
      end of the 18th century, had studied medicine in Vienna and Freiburg im Breisgau.
      His Freiburg doctoral dissertation is still of great interest today. In a first
      chapter it defines the term "insect", in a second it describes diseases insects
      can cause, and a final chapter discusses medical uses of insects. Quarin tried to
      unite traditional knowledge with new findings. His brief work is a survey of the
      knowledge of medical entomology in his time.

PMID- 9264960
TI  - [Progress of clinical practice in European armies (1750-1800)].
AB  - This article demonstrates that, before the 19th century and the Paris Clinical
      School, new medical practice and new clinical teaching based on pathological
      anatomy (of organs and of tissues) and surgical experience and therapeutic
      experimentation developed in the military milieu, specifically because of the
      "auspicious" conditions found there. Over time, this military clinical experience
      permeated civilian medical practice as military practitioners often moved into
      civilian practice and collaborated and exchanged experience with their civilian
      or ex-military colleagues. These conditions, in different forms and at different
      rhythms, in the great European powers, also favoured a rapprochement between the
      different groups of medical practitioners--physicians, apothecaries and surgeons-
      initially in the military milieu, and subsequently in civilian society as well.
      Finally, the article shows that the coercive disciplinary structure of the
      military, where sick or wounded soldiers were particularly constrained to act as
      subjects of experience, experimentation, clinical teaching and anatomico
      pathological research, was one of the conditions propitious to this growth of
      clinical practice.

PMID- 9264961
TI  - [Sculptor of The Cripple of the Geneva Museum of Art and History. An ancient
      Greek portrayal of hemimelia?].
AB  - An archaic Greek terracotta vase in the Art and History Museum at Geneva depicts
      a man deprived of his left arm and with two legs ending in a stump below the
      knees. Did he suffer from a traumatism (amputation), a mutilating disease or
      congenital malformation (hemimelia)? A survey of written and iconographic sources
      throws light on the methods and limits of ancient surgery, and on the chances of
      survival of abnormal children in archaic and classical Greece.

PMID- 9264963
TI  - [Between liberty and control, the private docents and medical teaching in Geneva
      between 1876 and 1917].
AB  - The University of Geneva was founded in 1876 with two sets of teachers
      established as competitive entities: the salaried professors and the nonsalaried
      privat-docents. The ease with which physicians obtained the title of privat
      docent, a series of abuses of that status and the professors' desire to manage
      teaching at all levels, resulted in a conflictual situation. The subsequent drive
      of professors to gain control over all teaching reveals tensions between the
      medical faculty and the political authorities, but also strains within the
      medical community itself. Ultimately, the result was the professors' leadership
      over the rest of the medical community.

PMID- 9264962
TI  - [Significance of cognitive processes in drug research in the 19th century-
      exemplified by nitroglycerin].
AB  - The history of the discovery and development of drugs is replete with examples
      where chance and "serendipity" have resulted in important advances of knowledge.
      In the case of nitroglycerin it can be shown that what appears to have been a
      chance discovery was actually the result of a sequence of selective perceptions
      by, and cognitive processes in individual researchers. The sources allow insight
      into various stages of the development of nitroglycerin, starting with the
      chemical synthesis as an explosive in 1846 and the first use in humans in 1847 to
      the discovery of a useful coronary drug. Homeopathic medicine contributed
      significantly to this process. Thus, the history of nitroglycerin is an example
      of an exchange of knowledge between otherwise separate realms of sectarian and
      orthodox medicine in the second half of the 19th century.

PMID- 9264964
TI  - [Albert Jesionek tracking cytomegalovirus disease].
AB  - The first publications concerning the peculiar cellular structures that later-on
      became the hallmark of cytomegalic inclusion disease, originated in the early
      20th century from German institutes. These early reports got into oblivion even
      before their significance and implications could be fully realized. The purpose
      of this study is to reconsider the contributions of Jesionek and other authors to
      the discovery of the "protozoa-like structures", based upon their publications
      and in accordance with the state of knowledge at that time.

PMID- 9264965
TI  - New trends in neurogeriatrics: from research to intervention in aging subjects
      with dementia. Proceedings and abstracts of the 7th National Congress of the
      Italian Society of Neurogeriatrics. Ville Ponti, Italy, 27-28 June 1997.

PMID- 9264966
TI  - [Magnetic resonance imaging for suspected femoral neck fractures].
AB  - Painful hip as a result of injury, with or without a history of trauma, is a
      common reason for referring elderly patients to the emergency room. The diagnosis
      of femoral neck fracture requires the combination of a physical examination, X
      rays, and in problematic cases, a bone scan. However, even this combination does
      not always provide a diagnosis. We present 50 patients with painful hip who
      complained of limp and reduced hip joint motion, but had no evidence of fracture,
      either on X-ray or bone scan. After conservative treatment, 5 patients with no
      history of trauma underwent hemiarthroplasty of the hip for displaced subcapital
      fracture. In addition, we present a case of subcapital fracture which was
      diagnosed only by MRI, in whom both X-rays and bone scan were considered normal.

PMID- 9264967
TI  - [Reporting maternal behavior during diarrhea in Bedouin children].
AB  - Diarrhea is still a major cause of morbidity and mortality among children in
      developing countries. The Bedouin population of southern Israel is in transition
      from a nomadic to a settled life-style. We examined maternal knowledge and
      reported behavior when their children had diarrhea. Mothers defined diarrhea as
      the passing of 4-5 stools per day. The most frequent signs of the illness were an
      increased number of watery stools with changes in either color or form. The most
      frequent symptom that prompted mothers to seek medical aid was blood in the
      stool. All mothers reported increasing fluid intake in their children during
      diarrhea, and most reported giving herbal tea. About half of the women avoided
      milk products and used special foods for the treatment of diarrhea. A quarter of
      the women reported stopping or decreasing the frequency of breast feeding during
      diarrhea. Reported cessation of breast feeding during diarrhea was associated
      with changing to special foods, and failure to note the onset of diarrhea or to
      recognize signs of dehydration. The withdrawal of breast feeding during episodes
      of illness and diarrhea is related to lack of knowledge regarding diarrhea. These
      data indicate that even in this population, with free access to preventive and
      curative medical care, there should be greater efforts to educate mothers to
      detect diarrheal disease and to maintain breast feeding during the diarrhea.

PMID- 9264968
TI  - [Managed care. Silver lining in the horizon or Pandora's box?].

PMID- 9264969
TI  - [Managed care--chances for health care in Germany?].
AB  - The incentives offered by the German health insurance make it rational for
      doctors and patients to adopt uneconomical attitudes that militate against the
      objective of providing economical health care tailored to individual needs.
      Managed care systems are a means of correcting this undesirable state of affairs.
      Implementation of managed care in Germany would however, appear to make good
      sense only when it is offered as a competitive alternative that guarantees the
      freedom of action and choice of all those involved.

PMID- 9264970
TI  - [Managed care. Economic evaluation. Necessity, possibilities and limits].
AB  - The German health care sector is faced with significant structural problems. In
      addition to existing shortcomings, serious new problems are already on the
      horizon, and threaten to aggravate the discrepancy between reasonable medical
      needs and the resources available to finance them. The resolution of this problem
      requires the use of new tools capable of helping physicians make economically
      sensible choices. While economic evaluation methods can help point up the
      economic consequences of various therapies they do nothing more than aid the
      physician to make decisions, and cannot be allowed to relieve him/her of this
      responsibility. The principle that medical ethics take preference of economic
      considerations must remain in place.

PMID- 9264972
TI  - [Bacterial endocarditis and endocarditis prevention. 2: Endocarditis prevention].

PMID- 9264971
TI  - [Non-motor symptoms of Parkinson disease. Significant impact on quality of life-
      using possible treatments].
AB  - In patients with idiopathic Parkinson's disease, not only the motor disorders,
      but also disturbances of the autonomic nervous system and the psyche need to be
      treated. With respect to the autonomic nervous system, such symptoms as
      hypersalivation, seborrhea, dysregulation of the cardiovascular system,
      disturbances of the gastrointestinal tract and bladder motility, as also sleep
      disorders predominate. Also seen in Parkinson's disease are such psychiatric
      complaints as depression, dementia and psychoses, which latter in particular may
      also be a consequence of dopaminergic replacement therapy. A number of
      therapeutic concepts are available for the treatment of these disorders, which
      are often extremely stressful for the patient and therefore require early
      treatment.

PMID- 9264973
TI  - [Incidence of Salmonella infections in general practice. Changes in diagnostic
      behavior or an actual increase?].

PMID- 9264974
TI  - [Magnetic fields of the brain facilitate stroke prevention. Interview by Dr. rer.
      nat. Anita Schweiger].

PMID- 9264975
TI  - [Suspicion of Chlamydia increases. Is the infectious myocardial infarct disease
      only the tip of an iceberg?].

PMID- 9264976
TI  - [Formation and effects of nitrogen monoxide (NO) in the vascular system].

PMID- 9264977
TI  - [Endothelial dysfunction and nitrogen monoxide (NO; nitric oxide)].

PMID- 9264978
TI  - [Nitrogen monoxide. Mediator or marker of chronic inflammation?].

PMID- 9264979
TI  - [Soluble guanyl cyclases. Key enzymes for therapeutic applications of the NO
      principle].

PMID- 9264980
TI  - [Nitric oxide in therapy of angina pectoris: nitrates or molsidomine?].

PMID- 9264981
TI  - [Nitric oxide donors in therapy of chronic heart failure].

PMID- 9264982
TI  - [NO and alternative inhalational therapy approaches in pulmonary hypertension].

PMID- 9264983
TI  - [Anti-arteriosclerosis effects due to stimulation of endogenous nitric oxide
      synthesis].

PMID- 9264984
TI  - [Inhibition of nitric oxide synthase in septic shock. Therapeutic limits and
      perspectives].

PMID- 9264985
TI  - [Acute renal failure, jaundice and thrombocytopenia in a 48-year-old patient].

PMID- 9264986
TI  - [35-year-old patient with eyelid and ankle edema after foreign travel].

PMID- 9264987
TI  - ["White clot syndrome"].

PMID- 9264988
TI  - [Predictive tumor diagnosis in hereditary tumor disposition?].

PMID- 9264989
TI  - [Early surgery of Dupuytren contracture].

PMID- 9264990
TI  - [Therapy indications in hypercholesterolemia].

PMID- 9264991
TI  - [Aortic stenosis].

PMID- 9264992
TI  - [Glucocorticoids in hematology and medical oncology].

PMID- 9264993
TI  - [Glucocorticoids in diseases of the gastrointestinal tract].

PMID- 9264994
TI  - [Glucocorticoids in pneumology].

PMID- 9264995
TI  - [Joint examination].

PMID- 9264996
TI  - [General principles of immunosuppressive therapy of diseases of rheumatic
      origin].

PMID- 9264997
TI  - [Conventional immunosuppression of chronic inflammatory systemic diseases].

PMID- 9264999
TI  - [Is there a reliable immunotherapy in infection?].

PMID- 9264998
TI  - [Immunosuppressive therapeutic modalities in chronic polyarthritis].

PMID- 9265000
TI  - [Immunosuppressive therapy in interstitial lung diseases and immunologically
      induced pneumonitis].

PMID- 9265001
TI  - [Immunosuppression in therapy of glomerulonephritis].

PMID- 9265003
TI  - [Indications for immunosuppressive therapy of chronic inflammatory bowel
      diseases].

PMID- 9265002
TI  - [Immunosuppressive therapy of autoimmune liver diseases].

PMID- 9265004
TI  - [Etiopathogenetic differentiation of inflammatory cardiomyopathy.
      Immunosuppression and immunomodulation].

PMID- 9265005
TI  - [33-year-old patient with postpartum myocardial infarct].

PMID- 9265007
TI  - [Impaired glucose tolerance].

PMID- 9265006
TI  - [Acute renal failure. Isolated manifestation of a systemic disease].

PMID- 9265008
TI  - [Odds ratio].

PMID- 9265009
TI  - [Primary prevention of cardiovascular diseases by lowering lipids].

PMID- 9265010
TI  - [Blood pressure monitoring in left ventricular hypertrophy].

PMID- 9265011
TI  - [Insulin analogs and new antidiabetic agents. Prospects in diabetes therapy].

PMID- 9265012
TI  - [Purpura as the leading symptom in internal medicine].

PMID- 9265013
TI  - [New technology for endonasal paranasal sinus surgery].

PMID- 9265014
TI  - [Standards for otorhinolaryngology--practical goal or wishful thinking?].

PMID- 9265015
TI  - [Audiologic classification of hearing retention after removal of acoustic
      neurinomas].

PMID- 9265016
TI  - [Guidelines/algorithms of the German Society of Otorhinolaryngology, Head and
      Neck Surgery. German Society of Otorhinolaryngology, Head and Neck Surgery].

PMID- 9265017
TI  - [Comments on the contribution by P. Plath. Comments on the revision of the
      Konigstein Guidelines].

PMID- 9265018
TI  - [Research in the psychosocial aspects of ENT tumor surgery (excluding
      laryngectomy): 4-part analysis of the literature. 1: Historical development].
AB  - We reviewed the available literature on the psychosocial aspects of head and neck
      cancer surgery from 1950 to 1995. Seventy-six empirical studies (from 12
      countries), 26 surveys, 67 other ENT-articles and 77 publications involving
      associated fields of research were used in this study. Part is a chronological
      description of the research now reported. This includes references to
      developments in head and neck surgery and in other fields, such as research on
      quality of life, self-concept, body-image, physical handicaps, disfigurement and
      coping. Part 2 analyzes existing empirical studies, while Part 3 presents the
      findings of the research. Part 4 formulates useful targets for future research.
      An extensive list of literature references is added in the appendix to part 4.

PMID- 9265019
TI  - [Endoscope-microscope combination (ENDO-OPMI) for endonasal paranasal sinus
      surgery].
AB  - The development of modern endonasal sinus surgery is fundamentally based on the
      introduction of optical instrumentation. Endoscopes and microscopes are commonly
      used in such surgery. We tested a new combination of a stereoscopic single
      channel endoscope with an operating microscope (ENDO-OPMI) for endonasal sinus
      surgery. This combination of the endoscope and microscope are connected in a way
      that results in a self-carried stereo-endoscope. To date, the ENDO-OPMI has been
      evaluated in cadaver studies and 7 cases of endonasal sinus surgery for chronic
      sinusitis. The trial was used to evaluate the clinical use of the current system
      and its possibilities for future developments. The ENDO-OPMI was demonstrated to
      be principally well-suited for endonasal sinus surgery. However, the current
      technical shortcomings make further developments necessary. Once these are
      implemented, the system should be superior to the use of an endoscope or
      microscope alone in endonasal surgery.

PMID- 9265020
TI  - [Microlight-guided spectrophotometry of the cochlea].
AB  - BACKGROUND: Intraoperative measurements of local intracapillary hemoglobin
      oxygenation of the human cochlea via the round window membrane have been shown to
      be possible using the Erlangen microlight-guided spectrophotometer. The aim of
      the present study was to develop a new microlight guide suitable for measurements
      in the round window niche and to evaluate electrophysiologically the possible
      impact of the procedure on the cochlea. METHODS: Measurements were made for
      wavelengths of 450 to 900 nm at a total power of 5.3 mW. The exit diameter of the
      light guide was 200 microns and the angle used was 20 degrees. The recording
      depth was about 250 microns. The atraumatic character of the spectrophotometry
      was demonstrated by monitoring the compound action potential (CAP) threshold
      tuning curve from 1 to 34 kHz in ketanest-anesthetized guinea pigs. RESULTS: CAP
      thresholds remained constant (0.3 +/- 3.9 dB SPL) during 3 to 30 min of exposure
      to the light. CONCLUSIONS: These results suggest that the spectrophotometry may
      be useful as a new technique for intraoperative monitoring of intracapillary
      hemoglobin without causing physiological deterioration of the cochlea.

PMID- 9265021
TI  - [Increased amplitude of distortion product emissions in the human caused by
      contralateral low intensity acoustic stimulation].
AB  - Distortion product otoacoustic emissions (DPOAEs) are probably based on the
      motile properties of the cochlear outer hair cells (OHCs), which are richly
      innervated by medial olivo-cochlear efferent nerves (MOCs). DPOAEs provide a
      stimulating model for functional exploration of the efferent system. The
      influences of contralateral acoustic stimulation were studied on the amplitude of
      ipsilateral DPOAEs at the frequency 2f1-f2. Fifteen ears of adults with normal
      hearing (7 women, 8 men, mean age; 23.1 +/- 4.2 years) were examined. Sound
      stimulation consisted of exposure to 6 successive series of contralateral pure
      tones at frequencies between 0.5 and 4.0 kHz and low intensities of 30 dB HL. DP
      grams were registered with f2 ranging from 708 to 6165 Hz. Contralateral pure
      tones in the frequency range above 750 Hz and with intensities of 30 dB HL
      increased the ipsilaterally registered DPOAE amplitudes. The results showed that
      this increase was frequency specific, at least for frequencies at 1 and 2 kHz.
      The frequency specificity was especially marked when ipsilateral f2 was near 1
      kHz. Contralateral frequencies of 3 and 4 kHz induced a significant, increasing
      effect, including ipsilateral frequencies around f2 = 3 kHz (or 4 kHz) and also
      lower frequencies around f2 = 1 kHz. Our results support the concept that the
      observed increase in DPOAE amplitudes is mediated by the medial olivo-cochlear
      efferent system. The rule of OHCs as a cochlear amplifier in the presence of
      contralateral low-intensity sound stimulation is discussed.

PMID- 9265022
TI  - [Value of smooth pursuit evaluation within the scope of clinical computerized
      nystagmography].
AB  - Testing gaze movements is very important for the detection of central vestibular
      diseases. The intent of this study was to clarify the pathological importance of
      partially disturbed and completely disturbed smooth pursuit movements. One
      hundred patients were analyzed and curves of smooth pursuit movements were
      classified into three groups of different deformations: i.e, regular, partially
      disturbed and completely disturbed movements. The correlation index of each curve
      was then calculated. In 16 patients qualitative analysis showed a completely
      disturbed result in the smooth pursuit test. Nine of the patients (56.3%) showed
      morphological signs of a central disease. Twenty-nine patients yielded a
      partially disturbed test result and in 2 of them (6.9%) a central pathological
      illness was uncovered. Patients with completely disturbed smooth pursuits showed
      the highest average binocular correlation index (1.44). Others with partially
      disturbed results gave an index of 1.24, while persons with regular smooth
      pursuits yielded a value of 1.17. Because of the scattering seen, it was not
      definitely possible to attach a correlation index to central disease. On the
      other hand, an index higher than 1.3 should arouse suspicion for a central
      illness. Only completely disturbed smooth pursuit movements frequently appear in
      connection with central diseases. As a rule, a partially disturbed result does
      not indicate diseases of the central nervous system.

PMID- 9265023
TI  - [Follow-up of patients with laryngeal contact granuloma].
AB  - A conservative approach (vocal rest, voice therapy, antibiotic treatment of
      infections and/or management of esophageal reflux) and microsurgery have been
      used to heal laryngeal contact granulomas. Unfortunately, recurrences have been
      found in most cases. In the present study we followed 45 patients after an
      initial diagnosis of a contact granuloma was made based on laryngoscopy and
      stroboscopy with video-documentation. All studies were conducted in the
      Department of Phoniatrics (University of Gottingen) during the past four years,
      with follow-ups made at 3 month-intervals up to 12 months after diagnosis. All
      patients were counselled using a focal psychosomatic approach. Follow-up was
      possible for 41 patients. Findings showed that 19 patients lost their contact
      granulomas completely without therapy, 12 of which occurred over a period to 13
      months after diagnosis. Seven patients underwent microsurgery at their own
      requests, with 5 developing recurrences when compared with the first diagnosis,
      15 patients still had a contact granuloma. Emotional strain in connection with
      specific personality traits seemed to operate as a significant variable in the
      remission of contact granulomas.

PMID- 9265024
TI  - [Rapidly enlarging occipital soft tissue tumor].

PMID- 9265026
TI  - [Displacement of a Schuknecht prosthesis in cranial MRI].

PMID- 9265025
TI  - [Merkel cell carcinoma. A rare differential keratoacanthoma diagnosis].
AB  - A 90 year old woman presented with a rapidly growing nodular tumor at the tip of
      the nose. Clinically, keratoakanthoma was tentatively diagnosed. Histological
      examination, however, revealed Merkel cell carcinoma. This case supports the
      necessity of a surgical excision with a subsequent histological examination even
      when the clinical aspect is suggestive for keratoacanthoma.

PMID- 9265027
TI  - [Responsible use of modern hearing aid technology. III: Improved speech
      discrimination in noise. Modern hearing aid technology in pediatric management].

PMID- 9265028
TI  - [Magnesium sulfate in obstetrics: finally recognized!].

PMID- 9265029
TI  - [Medical consensus practice guidelines in gynecology-obstetrics].

PMID- 9265030
TI  - [Uterine activity and premature delivery. Review of the literature].
AB  - OBJECTIVE: This paper reviews the recent literature on uterine activity during
      gestation with term and preterm delivery. METHODS: A review of the literature on
      uterine activity during gestation with term and preterm delivery was conducted by
      searching Medline file from 1990 to the present, using the key terms "uterine
      activity", "uterine monitoring", "preterm delivery", "term delivery". Additional
      references were accessed by cross referencing the bibliographie of the articles
      obtained through this search. RESULTS AND CONCLUSIONS: Contractions are
      infrequent in normal pregnancy. The mean 24-hour frequency of uterine
      contractions increase progressively with advancing gestational age. A strong
      diurnal rhythm is present from 24 weeks to the term with surge of contractions at
      night. These uterine activity noctural surges precede term delivery. These surges
      are lost in women who deliver prematurely. These studies suggest that early
      identification of increase in uterine activity is not the most appropriate
      intervention for prediction of preterm delivery. The reason lies in a flawed
      contraction-based theory of the pathogenesis of prematurity.

PMID- 9265032
TI  - [Carpal tunnel syndrome in pregnancy].
AB  - Analysis of 20 patients with 34 carpal tunnel syndromes (CTS) showed that CTS in
      pregnancy occurs generally between 30 and 40 years of age in both primiparous (n
      = 7) and multiparous (n = 13) women. The syndrome usually is most bothersome
      during the third trimester of pregnancy (n = 10) or during puerperium (n = 7).
      Clinically, CTS in pregnancy is very different from idiopathic CTS. Paresthesia
      frequently occurs during the daytime or is permanent and usually more troublesome
      than phenomena occurring at night. The Weber and Semmes Weinstein test, an
      objective measurement of hypoesthesia, is often positive. The
      electrophysiological findings are more serious and are different from those
      observed in idiopathic CTS. Mean nerve conduction velocity in the median nerve
      measured at the wrist is comparable in the two forms, but the frequency of
      neurogenic pattern is higher in pregnancy CTS. Conduction blocks are also much
      more frequent and concern motor (18%) or sensory (44%) conduction. These
      conduction blocks result from acute compression of the nerve due to hormone
      dependent tenosynovitis. Infiltrations are effective in 85% of the cases, but in
      some forms with very serious axonal loss, surgical release is justified.

PMID- 9265031
TI  - [Analysis of delivery facilities and conditions in 1991 in mothers of infants
      with birth weights below 1500 grams and/or gestational age under 33 weeks].
AB  - AIMS: To identify maternities (in terms of level of activity and linkage with
      pediatric services) where, in 1991, mothers gave birth to infants of gestational
      age less than 33 weeks and/or with birth weight under 1500 g. To analyse factors
      linked to the probability of choosing a particular maternity as place of delivery
      for this population and measure the impact of maternal transferts on the rates of
      deliveries. To estimate the number of neonate transferts which could be avoided
      with simple recommendations. To propose policies that would allow France to come
      closer to the results of other reference countries in term of management of
      obstetrical and neonate care. MATERIAL AND METHOD: We extracted from a
      retrospective sample of 84,279 births (out of a total of 770,148), 717 infants
      meeting previously defined criteria and related to the population described
      above, using univariate and multivariate analysis and logistic regression.
      RESULTS: The Odds-ratio for a delivery to take place in a maternity with a volume
      of more than 2000 deliveries a year, compared with those doing less than 300
      deliveries, is 4, 12. Only 15.8% of those deliveries took place in maternities
      linked to a level 3 pediatric unit (i.e where an intensive care neonates unit was
      located in the same building). 39.5% of births took place in level 1 maternities
      where no required pediatric service existed. Logistic regression techniques
      showed that the choice of a maternity for mother referral was more linked to the
      number of deliveries than to its level of pediatric services. In the studied
      population, 46% of the difference between the observed number of births in high
      volume maternities (compared to the expected number) could be explained by a
      maternal referral. The analysis of deliveries showed that for 34% of mothers who
      gave birth to a baby in a level 1 or 2 maternity, there was a possibility of
      being referred easily in a level 3 maternity. CONCLUSION: This study shows that
      the level of care of mothers at high risk of delivering a very premature and/or
      hypotrophic infant is far from international standards. Simple actions could
      double the number of births taking place in adapted maternities. We propose to
      both obstetricians and pediatrists, a common program to enhance the level of
      care.

PMID- 9265033
TI  - [A rare cause of postpartum hemorrhage: a genital thrombus].
AB  - Puerperal hematoma is a grave but fortunately rare hemorrhagic post-partum
      complication (occurring in less than 1:1000 deliveries). The hematoma arises due
      to detachment of para-vaginal conjunctive tissue. In this type of tissue, no
      natural hemostasis take place and the hematoma may spread into the
      retroperitoneal cavity. The different risk factors include primiparity,
      instrumental extraction of the foetus, pre-eclampsia, twin pregnancy and the
      presence of vulvo-vaginal varicose veins. External bleeding may not always be
      evident and other clinical symptoms may be delayed. Despite this, rapid course
      may still occur with drastic consequences. When a case is referred, an
      examination of the vulvo-vaginal region is mandatory, resuscitation and surgery
      performed immediately. If this fails angiographic embolization should be carried
      out. The prognostic outcome of this rare case of post-partum hemorrhagia is
      highly dependent on early diagnosis and rapid treatment involving close
      cooperation between obstetricians and anesthetists, and also of rapid
      embolization to prevent possible intractable hematomas.

PMID- 9265034
TI  - [Infectious complications after peridural obstetric anesthesia].
AB  - Infective complications after epidural anesthesia for delivery are uncommon. We
      reviewed 21 cases of epidural abscesses, 7 cases of meningitis and one
      spondylitis reported in the literature. These infections usually occurred in
      debilitated patients either by direct contamination at puncture or indirectly
      from a neighboring infection or from the blood stream. Prognosis depends on early
      diagnosis. The first manifestations are spinal stiffness or local pain. Signs of
      neurological deficiency come later at a stage when complete recovery is
      compromised. This emphasizes the importance of the clinical examination before
      delivery in search for skin or deep infections.

PMID- 9265035
TI  - [Maternal mortality in Brazzaville (1993-1994)].
AB  - OBJECTIVE: The purpose of this cross-section study is: to determine the maternal
      mortality rate in Brazzaville, Congo; to identify the main pathologies and
      associated risk factors; to suggest appropriate courses of a action in order to
      reduce the mortality rate. STUDY DESIGN: Records from the Brazzaville Central
      Hospital, the morgue and the city districts were used to study all the cases of
      women aged 15 to 44, who died from May 1 1993, to April 30 1994. Cases of
      maternal mortality were selected. RESULTS: One hundred forty-three cases of
      maternal death were registered for 35,000 live births, giving a rate of 408 per
      100,000 live births. Death in childbirth represents the third mortality factor in
      mothers-to-be, well behind AIDS and respiratory infections. The main direct
      factors are: obstetrical hemorrhagies (40.55%), post-abortion infections
      (18.85%), post-delivery infections (12.69%), eclampsia (11.18%), AIDS (4.19%).
      AIDS is the main indirect obstetrical and the primary mortality factor in mothers
      to-be. CONCLUSION: These findings suggest that the reduction of maternal
      mortality in Brazzaville has to be correlated with: the need for widespread
      information about the importance of pre-natal consultations, the need for
      efficacious action against the spreading of AIDS by common use of condoms, the
      fight against clandestine abortions, the provision of hospitals with appropriate
      equipment for the treatment of emergencies.

PMID- 9265036
TI  - [Short-term outcome of infants from triplet pregnancies. A series of 45
      pregnancies].
AB  - OBJECTIVE: To evaluate outcome of triplets pregnancies. METHODS: A retrospective
      study about children of 45 triplet pregnancies which occurred spontaneously or
      after assisted reproductive technologies. All were managed by the same
      obstetrical and pediatric team. RESULTS: Mean birth weight was 1800 g and 26% of
      children were very low birth weights (< 1500 g). There was no difference in the
      mean Apgar score of pH between first, second and third infant. Neonatal and
      perinatal mortality rate were respectively 60 and 75%. Incidence of respiratory
      distress syndrome was 29%, hyaline membrane disease 11%, intraventricular
      hemorrhage (grade 4) 1.3%, necrotizing enterocolitis 10.5% and bronchopulmonary
      dysplasia 4%. Only 10% of the infants were not hospitalized and were kept by
      their mother. 38% of the newborns had to be hospitalized in a Neonatal Intensive
      Care Unit, with a mean stay of 6 days. At birth, 34% of the babies required
      intubation for artificial ventilation. CONCLUSIONS: The main problem of triplet
      pregnancies is high prematurity.

PMID- 9265037
TI  - [Surgical treatment of twin-to-twin transfusion syndrome: coagulation of
      anastomoses with a Nd:YAG laser, under endosonographic control. Forty four
      cases].
AB  - Twin to twin transfusion syndrome occurs in 15% of monozygotic twin pregnancies
      and is characterized by a hemodynamic imbalance between the two fetuses. Survival
      is about 10% with expectant management. Our aim is to coagulate the placental
      vascular anastomoses joining the two fetal circulations on the placenta in order
      to prevent the consequences on the survivor when one dies in utero. Between
      November 1993 and April 1996, 44 patients were referred with severe twin to twin
      transfusion syndrome at less than 28 weeks' gestation. Nd:YAG laser coagulation
      of the placental vessels crossing the interamniotic membrane was performed under
      sono-endoscopic control. Forty-one patients have completed their pregnancy and 3
      are continuing uneventfully in the third trimester. Fifteen patients (36.5%)
      delivered 2 healthy infants who survived the neonatal period and are developing
      normally. Sixteen patients (41.5%) delivered one infant developing, normally
      after the death of the co-twin in the perinatal period. In ten cases (22%) both
      twins died in the perinatal period. Among the survivors, 3 (9%) present with
      neurological handicap at a median age of 9 months. Around 75% (31/41) pregnancies
      complicated by twin to twin transfusion and treated by fetoscopy delivered at
      least one healthy baby. These data confirm the feasibility of the technique and
      that morbidity in-the survivors is relatively low.

PMID- 9265038
TI  - [Comparative study of the short-term acceptability and tolerance of a new oral
      formulation of magnesium (TX 1341) and a reference magnesium].
AB  - This open, randomized study on 2 parallel groups compared the acceptability,
      digestive tolerance and observance of TX 1341, a new chewable magnesium tablet
      (OROMAG, Laboratoire Theramex) to that of a reference magnesium (MAG2,
      Laboratoire Theraplix). 179 patients warranting a magnesotherapy were treated for
      10 weeks either by 3 chewable lactate and citrate of magnesium tablets (TX 1341)
      each containing 120 mg of magnesium-element, or by 3 drinkable ampoules of
      pidolate of magnesium (each of 122 mg of magnesium-element). Acceptability was
      assessed at the end of the study by a semi-quantitative scale at four levels and
      digestive tolerance by closed questionnaire submitted before and after treatment.
      72.7% of patients treated by TX 1341 find the treatment agreeable against 46.1%
      with the reference magnesium (p < 0.01). The number of drops out linked to
      treatment is not significantly different in the two groups and they are virtually
      all linked to digestive problems. The two medications significantly lower the
      number of cases of constipation without noticeably increasing the number of cases
      of diarrhea. The comparison of the number of digestive symptoms which appeared
      under treatment only underline one significant difference between the 2 groups (p
      < 0.05): the appearance of 5 times less the number of abdominal pains with TX
      1341 (2 cases). Cases of irregular intake are significantly higher with the
      reference drug than with TX 1341 (respectively 23.7% and 8.5%; p < 0.01).

PMID- 9265039
TI  - [Intravenous leiomyomatosis of uterine origin with cardiac extension. A case
      report and review of the literature].
AB  - A case of intravenous leiomyomatosis of the uterus with extension into the heart
      discovered in a 34-year old patient who suffered from dyspnea is reported. The
      findings suggest that intravenous leiomyomatosis originates from the smooth
      muscle component of uterine veins. Only 30 cases of intravenous leiomyomatosis
      with intracardiac extension have been reported. Two-dimensional echocardiography
      showed an abnormal mass in the right atrium. Pelvic echography showed an abnormal
      mass in the pelvis. In case of cardiac involvement, spontaneous prognosis remains
      poor. The primary goal of surgery is the complete removal of the tumor.
      Hormonotherapy should also be considered in case of unresectable residual tumor.
      A long-term follow-up of patients after resection of intravenous leiomyomatosis
      is needed because recurrences up to 17 years after primary resection have been
      reported.

PMID- 9265040
TI  - [Congenital adenomatoid cystic malformation of the lung and renal polycystosis. A
      fetal case report and review of the literature].
AB  - We observed a plurifocal cystic adenomatoid malformation of the lung, Stocker
      class II, in a 21-week gestation fetus in association with polycystosis of a
      solitary medial kidney. There was no other notable abnormally. The caryotype
      could not be obtained. The association of these two congenital malformations is
      exceptional, only three similar cases have been reported in the literature. Two
      other cases of pulmonary adenomatoid malformations associated with nephromegaly
      with renal hyperlobulation have also been described. Whether this is a fortuitous
      association or not remains to be determined.

PMID- 9265041
TI  - [Rheumatoid purpura (or Schoenlein-Henoch syndrome) and pregnancy. Review of the
      literature and a case report].
AB  - Schonlein-Henoch purpura is a clinical syndrome of generalized vasculitis
      manifested by a petechial or ecchymotic purpuric skin rash, renal manifestations,
      abdominal pains (or gastro-intestinal bleedings) and arthralgias. This syndrome
      of unknown etiology usually occurs in children, predominantly in males, but has
      been reported in adults. Very little is known about the effect of this disorder
      on pregnancy and vice-versa. We report here our first case of Schonlein-Henoch
      purpura in a pregnant woman. A-38-year-old maghrebin woman gravida 4 para 3 was
      admitted to the hospital at 23 weeks'gestation with symmetrical arthralgias of
      the knees and ankles, and skin rash. Crops of nontender purpura were present on
      legs, buttocks and arms. The skin biopsy specimen revealed leukocytoclastic
      vasculitis with immunoglobulins A deposits. The prognosis has been excellent,
      kidney function was not compromised, and the outcome of the pregnancy was good.
      Only eight previous reports of Schonlein-Henoch purpura in pregnant women have
      been noted in the literature. The effect of pregnancy on the course of this
      syndrome remains unclear, and the treatment of relapses during pregnancy is
      unknown. Generally treatment is symptomatic only. The efficiency of steroid
      therapy has not been proved. During pregnancy the course of this disease is
      unforeseeable. Some patients' symptoms remain stable, other patients can suffer
      either new onset or exacerbation of the syndrome. The third trimester can be
      complicated by superimposed pregnancy induced hypertension, pre-eclampsia or
      eclampsia.

PMID- 9265042
TI  - [The value of ultrasonography in the early diagnosis of breast cancer].

PMID- 9265043
TI  - [Early menopause].
AB  - Early menopause due to an exhaustion of the ovarian follicles before the age of
      40 years occurs in approximately 1% of women in this age range. Clinical signs of
      estrogen deficiency with amenorrhea and sterility are usually confirmed by
      hypergonadotrope hypogonadism at laboratory tests. The syndrome is to be
      differentiated from gonadotrophine resistant ovaries and rare gonadotrope
      adenomas. Ovary biopsy shows more or less complete destruction of the follicles.
      There are many causes of early menopause including abnormal number or structure
      of chromosome X in 15-20% of the cases. Certain metabolic disorders and viral
      infections can also be incriminated. Finally surgery, radiotherapy or
      chemotherapy can be the cause of iatrogenic menopause. To determine prognosis,
      the woman's follicular capacity must be estimated. Estrogen therapy is currently
      the best choice to preserve chances for ovulation and pregnancy. When there is no
      remaining follicular capacity, ovum donation may be a solution. Finally, all
      patients should be given hormone substitution therapy due to the long-term risk
      of estrogen-progesterone deficiency.

PMID- 9265044
TI  - [Severe preeclampsia: management. Is conservative treatment justified?].
AB  - Severe preeclampsia is a major contributor to maternal and perinatal morbidity
      and mortality. This review was performed to assess the fetal and maternal
      benefits of allowing women presenting with severe preeclampsia between 24 and 32
      34 weeks of amenorrhea to continue their pregnancy following antihypertensive
      treatment. After ultrasound scanning to assess growth and biophysical state of
      the fetus, patients without deteriorating maternal conditions, were managed with
      volume expansion, antihypertensive drugs (as hydralazine, labetalol, nifedipine),
      anticonvulsants and prophylactic steroids to promote fetal pulmonary maturity.
      Previous studies have indicated that this conservative management is also
      possible with the HELLP syndrome, without an increase in maternal morbidity.

PMID- 9265045
TI  - [Hysteroscopy infection risk].
AB  - OBJECTIVES: The aim of this study is to evaluate the infectious risk of the
      hysteroscopy. METHODS: A prospective study was carried for nine months in the
      Belle-de-Mai maternity, in Marseille. We performed 81 operative or diagnostic
      hysteroscopies. A vaginal sample was achieved before the intervention and an endo
      uterine sample after the procedure. The statistical analysis used the Chi 2 test.
      RESULTS: Fifty per cent of the patients of whom vaginal sample was contaminated
      present an endo-uterine sample infected at the end of an operative hysteroscopy.
      In 25% of cases, whereas the vaginal sample was normal, the endo-uterine
      prelevment was infected. The relative risk of the endo-uterine bacterial
      contamination, in case of vaginal contamination was 8.75 during this procedure.
      Within diagnostic hysteroscopy, no patient with a normal vaginal sample, was
      contaminated. No patent infection was observed. CONCLUSION: There is a risk of
      endo-uterine contamination during hysteroscopy. This risk is higher when the
      vaginal sample is contaminated before the intervention. This risk is smaller than
      the infectious risk of hysterectomy.

PMID- 9265046
TI  - [Uterine leiomyosarcoma. Nine case reports, review of the literature].
AB  - OBJECT OF THE STUDY: To evaluate management and outcome of the treatment of
      uterine leiomyosarcoma. PATIENTS AND METHODS: Retrospective study of a series of
      9 patients treated for uterine leiomyosarcoma in this hospital from 1982 to 1994.
      RESULTS: The condition is rarely suspected preoperatively, diagnosis is usually
      made on histological examination of the operative specimen. The outcome is
      related to the mitotic activity of the tumour and to the infiltration of nearly
      structures. Surgery is the only effective treatment, chemotherapy is ineffective,
      adjuvant radiotherapy improves local control of the tumour but has no incidence
      on survival. CONCLUSION: In the absence of an effective adjuvant treatment
      uterine leiomyosarcoma bears a poor prognosis with the only exception of small
      non infiltrating tumours with a low mitotic activity.

PMID- 9265048
TI  - [In utero cellular therapy].

PMID- 9265047
TI  - [Retroperitoneal endometriosis infiltrating the utero-sacral ligaments. Technique
      and results of laparoscopic surgery].
AB  - OBJECTIVE: The goal of this study is to assess the efficiency of laparoscopic
      surgical treatment of pain for patients presenting deep endometriosis located on
      the uterosacral ligaments. STUDY DESIGN: We analysed a continuous series of 36
      patients treated by operative laparoscopy between January 1993 and April 1995. In
      all these cases treatment consisted of resection of all the uterosacral
      ligament(s) together with exeresis of all other endometriotic lesions. RESULTS:
      The results were assessed for all the patients with a minimum follow-up of one
      year. Patients who presented dysmenorrhea (29 cases) improved in 89.7% of cases
      (26 patients). Out of the 26 patients who presented deep dyspareunia, improvement
      was evident for 92.3% of cases (24 patients). The chronic pelvic pain suffered
      (17 cases) improved in 88.2% of cases (15 patients). Patients who benefited from
      an improvement rated it excellent or satisfactory in 80% of cases. CONCLUSION:
      These results demonstrate that provided the surgeon is highly skilled in
      laparoscopy, operative laparoscopy is efficient for the treatment of patients
      presenting painful symptoms related to deep endometriotic implants located on the
      uterosacral ligaments.

PMID- 9265049
TI  - [Genetics of Fragile X syndrome and its prevention].
AB  - The fragile X syndrome is the most common inherited form of mental retardation.
      Its prevalence is estimated to be one in 1000-4000 males and one in 2000-6000
      females, depending of the region. A large canadian population study in Quebec has
      shown a frequency of 1/260 carrier women. The fragile X syndrome was the first
      disease shown to be associated with "dynamic mutations", caused by an
      amplification of an unstable DNA sequence transmitted from generations to
      generations till a pathologic expression: mental retardation. The prevention is
      possible by a specific DNA analysis of patients and male and female carriers. It
      is possible to detect the mutation or the premutation in pregnant women and to
      propose a prenatal diagnosis by molecular study on chorionic villi samples or
      cultivated amniocytes.

PMID- 9265050
TI  - [Pulmonary doppler. Early results in normal pregnancies].
AB  - OBJECTIVE: The study of fetal lung circulation by means of pulmonary Doppler
      investigation. METHODS: Pulmonary Doppler ultrasound obtained with color pulsed
      Doppler with a 3.5-5 Mhz probe. Measure of resistance index and pulsatility
      index. PATIENTS: Forty seven pregnant women with singleton, between 18 and 39.5
      weeks gestation, were recruited to have a pulmonary Doppler ultrasound. 7 fetuses
      had intra uterine fetal growth retardation (IUGR). Overall, 50 Doppler velocity
      waveforms were measured. RESULTS: Resistance and pulsatility index were measured
      in all patients and at each examination. Resistance index (0.86 +/- 0.03) and
      pulsatility index (2.46 +/- 0.34) were found to be stable during pregnancy.
      Pulmonary pulsatility index in IUGR fetuses (2.71 +/- 0.33) were found to be
      higher than those in normotrophic infants (p = 0.006), whereas no difference was
      found in resistance index between the same subgroups. Moreover, no difference was
      found in pulsatility index measurements between preterm small-for-gestational age
      fetuses and normotrophic fetuses measured between 36 and 39.5 weeks gestation
      (2.68 +/- 0.31 vs 2.49 +/- 0.28). CONCLUSION: Pulmonary resistance index is not
      statistically different between nomotrophic and IUGR fetuses. In contrast
      pulmonary pulsatility index is significantly higher in IUGR fetuses when compared
      with normotrophic fetuses. Pulmonary Doppler ultrasound should be evaluated in a
      larger trial and correlation between Doppler measurements and fetal lung
      maturation should be studied.

PMID- 9265051
TI  - [Delivery of the overweight woman. Analysis of 115 patients].
AB  - OBJECTIVE: Our purpose was to assess the effect of weight gain during pregnancy
      on labor and delivery. Abnormal pregnancies were excluded from the study to avoid
      interaction with the management of labor. POPULATION AND METHODS: A retrospective
      monocentric case-control study was carried out. We analysed 115 pregnancies
      delivered in our institution between June 1994 and November 1994. The course of
      labor was studied in 2 groups of patients: a group of overweight patients and a
      control group. RESULTS: In the overweight patients, the frequency of induction of
      labor (25%) and of obstetrical analgesia (82%) was significantly higher than in
      the control group (respectively 7% and 64%), as well as the average duration of
      labour and the average duration of the rupture of the membranes. The rate of
      cesarean section was higher in the overweight patient group (16.7%) than in the
      control group (3.7%). The difference was not significant because of the small
      number of patients. CONCLUSION: These results show a more frequent requirement of
      induction of labour, analgesia, and cesarean section in overweight patients. This
      led us to propose a multidisciplinary management of overweight patients to
      minimize these different obstetrical risks during labor.

PMID- 9265052
TI  - [Operative laparoscopy and the adnexal cystic mass: where to set the limit?].
AB  - OBJECTIVE: To study the importance and the consequences of several managements
      options for adnexal cystic masses suspicious at ultrasound and/or at laparoscopy.
      MATERIAL AND METHODS: The importance of this question was evaluated by studying
      the correlation between the ultrasonographic appearance, the macroscopic
      diagnosis and the pathologic diagnosis in a series of 1098 patients operated over
      a 14-year period. The laparotomy rates obtained with the managements proposed
      were calculated by adding the laparotomies which would be performed because of
      the suspicious appearance to the laparotomies effectively performed in the
      department when treating the non suspicious masses. RESULTS: 32 of the 323
      suspicious cases at ultrasound were malignant. The negative predictive value of
      the laparoscopic diagnosis of malignancy was 100%. Depending on the management
      used, the incidence of laparotomy could have varied from 6.1% to 31.3% between
      1987 and 1991, and from 12.9% to 41.9% between 1992 and 1993. These results were
      related to preoperative selection. CONCLUSION: Using a simple management which
      includes diagnostic laparoscopy for masses suspicious at ultrasound and
      laparotomy for masses suspicious at laparoscopy, 80.1% of the patients would be
      treated by laparoscopic. This management seems reasonable until the long term
      results of large series about the laparoscopic treatment of ovarian cancer become
      available.

PMID- 9265053
TI  - [Embryotoxic factors and recurrent spontaneous abortions].
AB  - About 30% of recurrent spontaneous abortions remain unexplained by traditional or
      biological anomalies. The purpose of this work was to investigate embryotoxic
      factors produced by trophoblast stimulated lymphocytes from women with
      unexplained recurrent spontaneous abortion. The samples from 36 women with
      recurrent abortion before and during the next pregnancy and from 7 women with
      normal pregnancies and no history of spontaneous abortion have been tested. The
      lymphocytes were stimulated with trophoblastic extracts. The supernatants of the
      stimulated lymphocytes were tested in a 4-cell mouse embryo culture. The
      secretion of embryotoxic factor was determined if the number of life blastocysts
      was less than 50% of control values after 4 days. The lymphocytes from 59% women
      with 3 or more recurrent abortion produced the embryotoxic factor, this factor
      may be useful in predicting pregnancy outcome in women with a history of
      unexplained recurrent miscarriage. The embryotoxic factor might be a new cause of
      recurrent abortion and a predictive factor.

PMID- 9265054
TI  - [Use of an experimental Chlamydia trachomatis salpingitis model for evaluating
      the effectiveness of antibiotics and anti-inflammatory agents on fertility].
AB  - OBJECTIVES: An experimental model of Chlamydia trachomatis salpingitis was
      developed in mice to study the effect of combination antibiotic and
      antiinflammatory therapy on restoring fertility after tubal infection. METHODS:
      The mice were infected by injection via the ovarian bursa with a suspension
      containing a human strain of Chlamydia trachomatis sevar F. After treatment with
      antibiotics alone or in combination with antiinflammatory agents, fertility was
      studied at 4 months. RESULTS: With doxycycline and ofloxacine, there was not a
      significant difference in fertility between animals treated with antibiotics
      alone and those treated with antibiotics and antiinflammatory agents. However, a
      piroxicam and azythromycin combination improved fertility with a longer delay
      than with azythromycin alone. The most important factor appeared to be the
      antibiotic treatment. CONCLUSION: Associating an antiinflammatory agent was not
      shown to have a beneficial effect in reducing infertility after Chlamydia
      trachomatis salpingitis.

PMID- 9265056
TI  - [Monitoring of labor by fetal pulse oximetry in a case of fetal atrial
      ventricular block].
AB  - We present our experience with fetal pulse oximetry during labor monitoring in a
      case of fetal atrio-ventricular block. Fetal pulse oximetry is a recent technique
      of fetal monitoring. It is based on the photometric properties of hemoglobin and
      reduced hemoglobin. The continuous and noninvasive method measured fetal
      saturation in oxygen. It can detect fetal hypoxia, cause of acute suffering.
      Saturation was continuously greater than 40%. Spontaneous delivery raised no
      problem, either for the fetus or the mother.

PMID- 9265055
TI  - [A rare breast tumor: mammary fibromatosis. Two case reports and a review of the
      literature].
AB  - Aggressive fibromatosis of the breast is an uncommon benign disease. The clinical
      and X-Ray findings can simulate breast cancer. The diagnosis relies on histology.
      The typical feature of this disease is a locally aggressive but non metastasizing
      lesion with high recurrence rate. Treatment consists in wide excision. The role
      of radiation and drug therapy including antiestrogens has not been clearly
      established. Colonoscopy is indicated to research for an association with Gardner
      syndrome.

PMID- 9265057
TI  - [Uterine rupture. A case of spontaneous rupture in a thirty week primiparous
      gestation ].
AB  - Uterine rupture is one of the major complications of pregnancy. Most spontaneous
      uterine ruptures occur during labor in parturients with a scarred uterus.
      Spontaneous rupture where the uterus is unscarred are more rare and occur more
      frequently in older multiparous patients. Starting from a case of uterine rupture
      occurring in a 40 year-old primiparous women, we will present a review of the
      literature concerning cases of rupture in healthy uteri with no obvious cause.

PMID- 9265058
TI  - [The future of gynecology-obstetrics in Europe].
AB  - Medica Europe now exists and Gynecology-Obstetrics plays its role in several
      structures, associations and societies. One must be aware of these institutions
      as they will formulate recommendations for harmonizing training programs for
      future specialists in the European Community. An analysis of the current
      situation in the different EC countries shows that this harmonization is indeed
      necessary and that a certain number of recommendations for training programs for
      gynecologists-obstetricians have already been accepted.

PMID- 9265059
TI  - [Respective role of conservative and radical treatment of breast cancers].

PMID- 9265060
TI  - [Routine prenatal care in Europe: comparison of the experience of nine
      gynecologic-obstetric services in eight different countries].
AB  - OBJECTIVE: The purpose of this study was to compare the routine pre-natal
      surveillance carried out in nine European Gyneco-Obstetric units. MATERIAL AND
      METHOD: A survey was carried out between October 1992 and November 1993 with the
      aid of a questionnaire. The questionnaire contained 118 questions covering
      clinical examinations and explorations undertaken systematically during the
      first, second and third trimesters and at the end of pregnancy before delivery.
      To ensure that the replies were accurate, the survey was carried out on the spot
      in the units concerned with the head of the unit. RESULTS: The survey revealed a
      certain number of differences in the surveillance carried out in the various
      units. The units did not all carry out systematic blood tests for toxoplasmosis,
      AIDS and hepatitis B at the first examination. The same applied to fasting blood
      glucose and the bacterial culture of the urine. Nor did all the units
      automatically undertake vaginal examination during the second and third
      trimesters and the English departments were not all convinced of the need for
      systematic ultrasound tests. Only five of the nine units undertook routinely
      cardiotocographic recordings of the fetal heart rate at the end of the pregnancy.
      CONCLUSION: The differences observed in the various surveillance procedures
      simply reflect our uncertainty regarding the different tests we use to monitor
      pregnancies. At a time when financial constraints are forcing us to make choices,
      there is an urgent need to assess the effectiveness and the cost of the various
      elements of our prenatal monitoring.

PMID- 9265061
TI  - [Peritoneal tuberculosis. Value of laparoscopy].
AB  - We report 6 cases of tuberculous peritonitis, focusing on the contribution of
      laparoscopic exploration. The initial diagnosis was erroneus in all cases: the
      polymorphous clinical presentations suggested another infectious disease or
      cancer disease. Laparoscopy was performed in 5 patients who had ascitis and in 1
      with plastic peritonitis. At laparoscopy, the peritoneum showed miliary
      granulations and inflammatory adherences on the visceral or parietal sheats.
      Bacteriological analyses of the ascitic fluid were positive in only one case. The
      diagnosis was confirmed after culture of biopsy specimens and identification of
      the Kock bacilli or on the basis of objective evidence of an epithelioid giant
      cell granuloma with caseous necrosis. Outcome was favorable after appropriate
      antibiotic therapy.

PMID- 9265062
TI  - [Extra-uterine pregnancies after in vitro fertilization. Six case reports].
AB  - Ectopic pregnancies after in vitro fertilization (IVF) are more frequent because
      of the development of assisted reproductive technology. This retrospective study
      analysed 6 cases of ectopic pregnancy after IVF from the "clinique du Parc"
      (Tours) during a 3-year period. Tubal disease was found to be the main risk
      factor for ectopic pregnancy after IVF heterotopic pregnancy may occur and its
      diagnosis is often difficult. Management of these ectopic pregnancies included
      salpingectomy in most cases. Bilateral salpingectomy before IVF may be discussed
      in cases of severe chronic infectious tubal disease. However, interstitial
      pregnancy is always possible after tubal occlusion.

PMID- 9265063
TI  - [Panorama of uropathies discovered during the prenatal period. 147 cases].
AB  - OBJECTIVES: The aim of this study was to establish the panorama of uropathies
      discovered during the antenatal period and to analyze the explorations performed.
      Pregnancy outcome and infant prognosis was also recorded. METHOD:
      Ultrasonographic imaging revealed dilatation in 62.5% of the cases, parenchymal
      anomalies in 26.3% and unilateral or bilateral agenesia in 11.2%. The percentage
      of abnormal karyotypes was 4.76% for all urorenal symptomatologies. These
      abnormal karyotypes corresponded to 10% of those performed in 17 fetuses, urine
      puncture was used in order to assess in utero renal function. There were 113 live
      births, 31 medically termined pregnancies and 3 spontaneous abortions. Among the
      113 live infants, 12 died during the post-natal period. Thirty-two infants were
      considered to be normal and 69 had an urorenal malformation, including 2 infants
      with pre-end-stage renal failure at 4 and 3 years. CONCLUSION: It is uncommon to
      discover an urorenal malformation at prenatal ultrasonography. The main problem
      is antenatal management and evaluation of prognosis. Urine puncture and in utero
      derivation are discussed. When no other reliable factors affecting fetal
      prognosis are available, puncture of fetal urine provides useful information for
      management although the technique remains under debate.

PMID- 9265064
TI  - [Cervical maturation by repeated applications of prostaglandin E2 gel. 186
      cases].
AB  - OBJECTIVE: A prospective clinical trial of cervical ripening with intracervical
      prostaglandin E2 gel in repeated administrations was performed. STUDY DESIGN: One
      hundred eighty-six patients were enrolled in this prospective trial between
      01/01/89 and 31/12/93. these patients with unripe cervix (Bishop score < 5)
      required induction of labor because of pregnancy disorders. Mean patient age was
      28.2 years (range 15 to 43), mean gestational age was 39.2 week's gestation
      (range 33 to 43) and mean parity was 1.8 (range 1 to 10). Our exclusion criterias
      were as follow: twin pregnancies, breech presentation and premature rupture of
      membranes. A 0.5 mg prostaglandin E2 gel was administered into the cervix every
      four hours maximal of three doses before induction of labor with oxytocin.
      Maternal and neonatal results were reviewed. RESULTS: Patients required a single
      dose of gel in 19.9% of cases, two doses in 26.3% and three doses in 53.8%.
      Induced labor during cervical ripening occurred in 55.4% of patients. A cesarean
      section was necessary in 22% of cases. This rate was both significantly related
      to the initial Bishop score and to the Bishop score at the end of the procedure.
      Patient with induced labor during the cervical ripening had a significantly lower
      cesarean section rate compared to these who needed induction with oxytocin (10.7%
      versus 33.8%; p < 0.01). The uterine hyperstimulation rate was 1.6%. A 1 min
      Apgar score less than 7 occurred in 1.1% of neonates. COMMENTS: Our results do
      not demonstrate benefit of repeated administration comparison to a single
      administration described in literature. Maternal and neonatal morbidity is low in
      this study but cervical ripening should be used only when pregnancy disorders
      require prompt delivery within twenty-four hours.

PMID- 9265065
TI  - [Medical-social outcome of 59 infants born to addicted mothers].
AB  - BACKGROUND: Follow up of children born to drug-addicted mothers is difficult
      because of social context. The aim of this study was to determine the precise
      outcome in a cohort of infants from two neonatal units. POPULATION AND METHODS;
      Analysis of perinatal and follow up data of 59 infants born to drug-addicted
      mothers, admitted from 1988 to 1993 in the neonatal units of Colombes and
      Neuilly. RESULTS: Perinatal data: very poor social context; 100% addiction by
      opiates and very frequent polyintoxication; 21% HIV + mothers; 54% came later or
      not at all to prenatal care; 34% prematurity and 46% intrauterine growth
      retardation; 80% neonatal withdrawal symptoms. Precise follow up data is known
      for 95% of the infants at the age of 1 to 7 years: 5% died during the first year
      of life; 51% are living with their family (with or without their mother); 36% are
      in institutions or foster homes, and 8% are fully adopted; among 41 newborns
      discharged from neonatal unit to their mother, 34% have been secondarily placed
      by Child Protection Services. The only severe sequelae were not related to drug
      direct effect: 5 neurologic or respiratory chronic impairment related to
      prematurity, and 3 asymptomatic HIV + children; a few moderate behavioral
      problems appear to be related to social familial context. Among the 51 mothers, 6
      died (5 by overdose) 19 are severely addicted, 10 have stopped addiction but 2
      are HIV +, and 16 are lost to follow up. CONCLUSIONS: Analysis of this cohort and
      of the literature suggest a need for changing our perinatal strategies to
      ameliorate medico-psycho-social care of these pregnancies, mothers and infants,
      with or without methadone maintenance programs; these strategies have been proved
      to prevent perinatal problems (specially prematurity), and to improve mother
      infant attachment.

PMID- 9265066
TI  - [Complications of laparoscopy caused by trocars. Preliminary study from the
      national registry of the French Society of Gynecologic Endoscopy].
AB  - OBJECTIVE: To describe laparoscopic complications due to trocar insertions and to
      define their prevention as well as their risk factors. STUDY DESIGN: The SFEG
      registry of laparoscopic complications was used for our study; 26 complications
      due to trocar insertions were recorded to this day by the register including 12
      vascular injuries, 9 bowel injuries, 3 bladder perforations and 2 incisional
      herinas. In order to avoid accidents of this technique, patient profile,
      laparoscopy indications, trocar type, diagnosis and treatment of the
      complications as well as the outcome must be defined. RESULTS: Whatever the
      operator's experience, the indication of laparoscopy and the trocar type some
      patients seem to have complications at laparoscopy: 70% of studied group had
      prior surgical treatment and 50% were over weight. However, it appeared that
      safety rules were not been taken into account for one-third of the trocar
      injuries. Consequently, laparotomy was used by the same surgeons for these
      complications in 89% of cases, laparotomy was delayed in 27% of the cases.
      CONCLUSION: In order to prevent laparoscopic complications, the surgeon must (i)
      inform the patients about risks which may occur, (ii) be careful, and (iii)
      declare each complication to a national registry such as the SFEG registry.

PMID- 9265067
TI  - [Is the Mauriceau maneuver deleterious? Study of 103 cases].
AB  - The Mauriceau manoeuvre has a poor reputation in France where some obstetricians
      believe it leads to an increase in the number of neonatal traumal injuries. To
      evaluate this hypothesis we examined the results of a personal series of 103
      cases of breech extraction where foetal head extraction was performed using the
      Mauriceau manoeuvre. Our study showed that the level of traumal complications was
      not worse than that of the general neonatal population. We therefore conclude
      that this active and organized method of breech delivery is safe and provides a
      young obstetrician with valuable experience of practical obstetrical
      manipulation.

PMID- 9265068
TI  - [Lymphatic drainage of the uterus. Preliminary results of an experimental study].
AB  - We carried out an experimental study on the lymphatic drainage of the uterus in
      11 female cadavers. We performed 5 injections of a colored fluid in the corpus
      uterinum and 6 in the cervix. We observed 2 main routes along the external iliac
      vessels. The first was anterior and drains the lower limb. The second is medial
      and posterior to the external iliac vessels and drained the uterus (2.4 lymph
      nodes/side). The number and location of the lymph nodes varied between subjects
      but also in the same subject (45.5% of cases). The cervix was essentially drained
      to lymph nodes located on the posterior aspect of the external iliac vein,
      especially near the hypogastric artery origin. We did not observe any direct
      connexion between the cervix and the para-aortic area. The corpus uterinum was
      drained to the lymph nodes located in the lateral part of the parametrium and or
      under the external iliac vein. One other main route ran along the infudibulo
      pelvic ligament. These findings confirm that the first lymph nodes metastases of
      the cervical carcinoma are under the external iliac vein. and particularly near
      the hypogastric artery. On the other hand, endometrial carcinomas spread along
      two lymphatic connections: one extending to the external iliac area and another
      to the para-aortic area. These results have to be considered in order to define
      lymphadenectomy margins for these cancers.

PMID- 9265069
TI  - [Malignant non-Hodgkins lymphoma manifested in an ovarian tumor. Five case
      reports].
AB  - Five cases of non-Hodgkin malignant lymphoma (NHML) presenting as ovarian tumours
      are reported. All corresponded to disseminated lymphomatous disease, none was of
      low grade. Ultrasound showed a solid, most often homogeneous, hypoechoic,
      bilateral mass in 4 of 5 cases. Its association with many lymph nodes and mainly
      parenchymal localisation suggested of the NHML. Only histologic and
      immunohistochemical findings may provide the final diagnosis. The biopsy for
      those studies should be obtained as least invasively as possible because
      treatment of NHML is chemotherapy.

PMID- 9265070
TI  - [Agenesia of the canal of Arantius. A case report].
AB  - Looking for the etiology of hydramnios which became symptomatic at 21 weeks'
      gestation ultrasonography revealed a hepatic vascular abnormality without other
      symptoms. The suspected diagnosis was agenesis of the ductus venosus with
      creation of a high grade arteriovenous shunt between the umbilical vein and the
      inferior vena cava. Agenesis of the ductus venosus may be one expression of the
      different possible systemic-portal-umbilical abnormalities. Physiological
      consequences vary according to the type of substitutive anastomoses.

PMID- 9265072
TI  - [Mauriceau's maneuver; comment].

PMID- 9265071
TI  - [Meckel syndrome. Update on a recurrent case].
AB  - Meckel's syndrome is an autosomal recessive disorder classically defined by
      occipital encephalocele, multicystic kidneys and polydactyly. However, a very
      wide phenotypic spectrum is characteristic of Meckel's syndrome. The prenatal
      diagnosis of this lethal syndrome is approached with ultrasound examination. The
      karyotype has to be done in order to make the differential diagnosis, especially
      with Trisomy 13 or 18. The rate of the Meckel's syndrome's gene is 1/400. The
      isolation of the specific gene will be soon helpful to define the Meckel's
      syndrome precisely.

PMID- 9265073
TI  - Research and technology transfer in computerized electrocardiology. Proceedings
      of the 21st annual ISCE conference. Chandler, Arizona, April 20-25, 1996.

PMID- 9265075
TI  - Selection and adaptation of cells expressing major histocompatibility complex
      class I-specific receptors of the natural killer complex.

PMID- 9265074
TI  - Complexity and redundancy in the pathogenesis of asthma: reassessing the roles of
      mast cells and T cells.

PMID- 9265076
TI  - What can we learn from the morphology of Hebrew? A masked-priming investigation
      of morphological representation.
AB  - All Hebrew words are composed of 2 interwoven morphemes: a triconsonantal root
      and a phonological word pattern. the lexical representations of these morphemic
      units were examined using masked priming. When primes and targets shared an
      identical word pattern, neither lexical decision nor naming of targets was
      facilitated. In contrast root primes facilitated both lexical decisions and
      naming of target words that were derived from these roots. This priming effect
      proved to be independent of meaning similarity because no priming effects were
      found when primes and targets were semantically but not morphologically related.
      These results suggest that Hebrew roots are lexical units whereas word patterns
      are not. A working model of lexical organization in Hebrew is offered on the
      basis of these results.

PMID- 9265077
TI  - The first 25 years of the American College of Veterinary Internal Medicine.

PMID- 9265079
TI  - [Programs of early detection of breast cancer and access of mammography in
      Spain].
AB  - BACKGROUND: We studied availability to mammography among Spanish women aged 40 to
      70 years, variation in use of the mammography by autonomous community, and the
      situation and importance of breast cancer screening programs among other factors,
      in the access to mammography. SUBJECTS AND METHODS: A cross-sectional population
      survey was conducted in 1994 in a sample of 3,218 women. A questionnaire was used
      to collect data on the variable access (receipt of at least one mammogram in the
      last 2 years) as well as different access-related variables. Information on
      breast cancer screening programs was collected by contacting the responsible
      institutions. We considered that a program had total coverage if it included all
      the municipalities in the province and partial if it did not include all
      municipalities. RESULTS: Twenty-eight percent of women had performed a mammogram.
      This proportion varied among autonomous communities (AACC) from 11.5 to 73.8%.
      Breast cancer screening programs existed in 8 AACC. The multivariant analysis
      revealed an association between access to mammography and the existence of a
      screening program, especially when the later had total coverage (OR = 7.64; 95%
      CI = 5.24-11.10). An association was also found between access to mammography and
      physician-related factors, place of residence and attitudes of women toward
      mammography. CONCLUSIONS: Less than one third of women aged 40-70 have performed
      a mammography in the last 2 years, and this proportion varies among AACC.
      Gynecologist visits and the existence of breast cancer screening programs are
      fundamental factors in the access to mammography in Spain.

PMID- 9265078
TI  - Maturational differences in chlorpyrifos-oxonase activity may contribute to age
      related sensitivity to chlorpyrifos.
AB  - Chlorpyrifos (CPF), a commonly used cholinesterase-inhibiting insecticide, is
      lethal at much lower doses to young animals than adults. To explain this higher
      sensitivity in younger animals, we hypothesized that young rats have less
      chlorpyrifos-oxonase (CPFOase) activity than adults. To test this hypothesis,
      CPFOase activity was measured in the brain, plasma, and liver of male, postnatal
      day 4 (PND4) and adult (PND90) Long-Evans rats. CPFOase is biochemically defined
      as a Ca(2+)-dependent A-esterase that hydrolyzes chlorpyrifos-oxon (CPFO), the
      active metabolite of CPE. No brain CPFOase activity was detected at either age.
      Plasma and liver CPFOase activities were markedly lower at PND4 compared to
      adult: PND4 plasma and liver CPFOase activities were 1/11 and 1/2 the adult
      plasma and liver activities, respectively. Because the Km of CPFOase activity was
      high (i.e., 210-380 microM), it was important to determine if this CPFOase
      activity could hydrolyze physiologically relevant concentrations (i.e., nM to low
      microM) of CPFO. This was accomplished by comparing the shifts in the tissue
      acetylcholinesterase (AChE) IC50 for CPFO in the presence or absence of CPFOase
      activity. One would expect an increase in the "apparent" IC50 if CPFOase
      hydrolyzes substantial amounts of CPFO during the 30 minutes the tissue is
      preincubated with the CPFO. In the adult, both plasma and liver AChE apparent
      IC50 values were higher in the presence of CPFOase activity, suggesting that the
      CPFOase in those tissues was capable of hydrolyzing physiologically relevant
      concentrations of CPFO within 30 minutes. In young animals, however, there was
      less of a shift in the IC50 curves compared to the adult, confirming that the
      young animal has less capacity than the adult to detoxify physiologically
      relevant concentrations of CPFO via CPFOase.

PMID- 9265080
TI  - [Use of screening mammography and its demographic and risk determinants in women
      25 to 65 years of age].
AB  - BACKGROUND: To know the utilization of the screening mammography among women from
      25 to 65 years old in an urban health zone, where there is not an specific
      screening program for breast cancer. To detect the demographic and risk
      determinants that are involved in the mammography screening use. SUBJECTS AND
      METHODS: A sample of 1,240 women were interviewed consecutively as they visited
      their physician. Risk factors, sociodemographic variables and use of health
      services were analyzed. The associated variables with the use of mammography
      screening were determined by univariant analysis. A multiple logistic regression
      model was designed to identify the variables independently associated with the
      use of mammography screening. RESULTS: The percentage of interviewed women who
      have completed at least one mammography screening in the last three years has
      been 10.2 +/- 3% (confidence level: 95%), 68.3% of them were under 50 years old.
      The variables independently associated with the use of mammography screening
      were: age (OR = 1.08); routine visit to the gynecologist (OR = 8.13); educational
      level (primary: OR = 2.44, secondary: OR = 3.66, university: OR = 7.43, no
      schooling: reference level); and knowledge about the benefits of mammography
      screening (OR = 6.15). Family history of breast cancer and the other risk factors
      were found not to be associated with the use of mammography screening.
      CONCLUSIONS: The use of mammography screening among women from 25 to 65 years is
      inadequate according to the age and other risk factors. Mammography screening
      among women with a family history of breast cancer and those over 50 years old is
      underused, so it would be recommended and their use increased for these women.
      But women under 40 years old without family history of breast cancer have to be
      dissuaded from undertaking such a screening.

PMID- 9265081
TI  - [Adverse effects associated with antimalarial chemoprophylaxis].
AB  - BACKGROUND: To evaluate the frequency and type of adverse drug reactions
      associated to the antimalarial chemoprophylaxis advised to travellers visiting
      endemic areas. SUBJECTS AND METHODS: We included the travellers who from july
      1992 to june 1994 came to the Travellers Advise Department and made short-term
      travels to areas with malarial infection risk. The adverse drug reactions were
      reported by the travellers through a questionnaire handed at the consulting room.
      The pharmacological regimens advised were: a) chloroquine base 5 mg/kg/week. b)
      chloroquine base 5 mg/kg/week + proguanil 100 mg/day if weight less than 55 kg
      and 200 mg/day if weight more than 55 kg. c) mefloquine 250 mg/week. RESULTS: We
      evaluated 1,054 questionnaires for the study. The 18.4% of the travellers
      reported adverse drug reactions. The 12.4% of the travellers who were on
      chloroquine, the 17.2% of those who were on chloroquine + proguanil and the 20.3%
      from mefloquine group presented adverse drug reactions (differences without
      significance). Comparing the regimens studied, we observed that neuropsychiatric
      reactions were more frequent in the mefloquine group (p < 0.01), the
      gastrointestinal reactions were less common in the chloroquine group (p = 0.04)
      and the transitory eye disorders were more frequent in the chloroquine +
      proguanil group (p = 0.01). In the mefloquine group the travellers with adverse
      drug reactions had a significantly lower weight than those who did not present
      them (p < 0.01). CONCLUSIONS: The adverse drug reactions reported agree with the
      toxicologic profile described in the literature about these drugs. Mefloquine
      presents an outstanding neuropsychiatric toxicity and is worse tolerated in low
      weight patients.

PMID- 9265082
TI  - [Carbon monoxide poisoning].

PMID- 9265083
TI  - [Early detection of breast cancer].

PMID- 9265084
TI  - [Association of alpha and beta thalassemia with alpha gene triplication in one
      family].
AB  - We describe the haematological data and molecular results of a native family from
      Cadiz in that one is produced the a within heterozygous beta 0 thalassaemia (IVS
      1, nt 1-G-->A), heterozygous alpha+ thalassaemia (-alpha 3.7) and alpha gene
      triplication (alpha alpha alpha 3.7). PATIENTS AND METHODS) We are studied 7
      members to a family composed by father (I1), mother (I2) and five children (II1,
      II2, II3, II4, II5). The molecular biology study of the alpha gene was realized
      by Southern blot method using the restriction enzymes Bam HI, Bgl II and Eco RI
      and hybridized with alpha probe of the plasmid PRB 1 (fragment of 1.5 Kb digested
      with the enzyme Pst I). The genes were studied by the technique of the polymerase
      chain reaction (PCR), modified according to designated method "Amplification
      Refractory Mutation System" (ARMS). RESULTS: The father (I1) presents an
      interaction of therozygous beta 0 thalassaemia with heterozygous alpha +
      thalassaemia (beta 0/beta 1;alpha alpha/-alpha 3). The mother (I2) shows an alpha
      gene triplication (beta A/beta A: alpha alpha alpha 3.7/alpha alpha). Finally the
      children are expressed 5 possibilities: II4 he is normal (beta A/beta A; alpha
      alpha/alpha alpha), II2 he has alpha gene triplication (beta A/beta A; alpha
      alpha/alpha alpha alpha 3.7), II3 he has heterozygous beta 0 thalassaemia (beta
      0/beta A; alpha alpha/alpha alpha), II5 he has interaction between heterozygous
      beta 0 thalassaemia and heterozygous alpha gene triplication (beta 0/beta A;
      alpha alpha alpha 3.7/alpha alpha) and II1 presents an interaction between a
      heterozygous beta 0 thalassaemia and together with the lost of one alpha gene in
      one chromosome he also presents a alpha gene triplication in other one (beta
      o/beta A; alpha alpha/alpha alpha). The hematological data of II5 corresponds to
      a intermediate thalassemia with not transfusion dependent feature an opposite to
      II1 that presents a heterozygous thalassemic trait features with 4 alpha genes.
      DISCUSSION: The phenotypical expression of the different interactions of these
      mutations in this family, points out, the relevant role that the unbalance
      globins chains plays in the pathogenesis and development of the clinical
      manifestations of the patients with the thalassaemia syndromes.

PMID- 9265085
TI  - [Collagenous and lymphocytic colitis].

PMID- 9265087
TI  - [Comments on Clinicopathological Conference by Residents, 6, 1996].

PMID- 9265086
TI  - [Churg-Strauss syndrome and antineutrophil cytoplasmic antibodies].

PMID- 9265088
TI  - [HIV nephropathy and amyloidosis].

PMID- 9265089
TI  - [Sepsis caused bt Leuconostoc cremoris, neutropenia and human immunodeficiency
      virus infection].

PMID- 9265090
TI  - Molecular staging of cancer: is it time?

PMID- 9265091
TI  - Crash and boom: the rise and fall of biotechnology.

PMID- 9265092
TI  - [A statistical study of 206 patients suffering from malignant neoplasms of the
      cervicofacial area].
AB  - This study focuses on the importance of early diagnosis in the oncological
      resolution of neoplasia of the cervico-facial district. In a sample of 206
      patients suffering from neoplasia of the cervico-facial district, the authors
      found a greater incidence of pathology between the 6th and 7th decades of life, a
      finding that confirms the enhancement of etiopathogenetic factors over time. The
      oral cavity represents the site predominantly affected by this neoplasia with an
      incidence of 57.3%. Epidermoid carcinoma represents 61.7% of the histological
      types examined. The treatment protocol used in 167 patients depending on the
      clinical stage and the general conditions of the patient was as follows:
      multimodal in patients at stage 3 and 4 with a minimum survival rate at 12 months
      of 75% and 58% respectively, predominantly surgical in patients at stage 1 and 2
      with a survival rate of 94.4 and 89.7% respectively.

PMID- 9265094
TI  - [Skeletal changes induced by radiotherapy. A study of subjects with
      retinoblastoma. II].
AB  - The authors examine the dental and skeletal alterations consequent to the use of
      radiotherapy as the elective method of treating retinoblastoma, an endobulbar
      neuroectodermal tumour typical of early infancy. The authors revise the basic
      concepts of radiobiology and the modifications induced by radiation in developing
      tissues with reference to both alterations at a microscopic (histological) level
      and those at a macroscopic level, namely of a morphological and structural
      nature. In the first part of the study the authors examine the damage to dental
      structures relating to both developing tissues and damage to mature tissue. The
      second part of the paper analyses radiation damage on cartilage and bone tissues
      in the process of formation and the authors present their documentation in the
      form of iconographic and radiographic material together with an esthetic face
      analysis performed using Rickettz's method in three cases referred to their
      attention.

PMID- 9265093
TI  - [Non-Hodgkin's lymphomas of the oromaxillofacial area. A clinical contribution].
AB  - The authors present a clinico-statistical review (January 1987-December 1994) of
      19 patients with non-Hodgkin's lymphoma of the oro-maxillo-facial region,
      diagnosed in the Dentistry Department of the University of Verona in
      collaboration with the Haematology Department. Particular attention has been
      devoted to the localisation, symptomatology, diagnosis and histological typing of
      non-Hodgkin's lymphoma of the maxillofacial region, stressing the importance of
      diagnosis and staging, based on a multidisciplinary approach, in order to be able
      to plan the most appropriate therapeutic management of patients with the disease.

PMID- 9265095
TI  - [The sound during mandibular joint kinematics. The diagnostic, epidemiologic and
      prognostic elements].
AB  - Articular noise is one of the most frequent signs of a dysfunction of the
      masticatory system, but its clinical importance is often low. However, it is
      necessary to recognise the main characteristics of this pathological aspect of
      the temporomandibular arthrokinematics, such as type (soft or rough) and timing.
      The reliability of clinical methods versus electronic instrumentation for
      recording temporomandibular joint sounds is emphasized, when applied under
      uniform conditions. The surveys about the correlation factors (occlusal,
      anatomical, gender and age due, psychobehavioural) did not show unilateral
      results. In any case, the epidemiological data and the clinical experience over
      the years regarding articular sounds, do not make us able to detect the stage of
      the internal derangement of the affected joint. The prognosis is not severe for
      asymptomatic patients; on the contrary, the identification of some joint crepitus
      and, at the same time, the presence of pain and/or other dysfunctional symptoms
      needs immediate treatment.

PMID- 9265096
TI  - [Myositis ossificans of the pterygoid and temporal muscles with metachronous
      contralateral involvement].
AB  - After reviewing the literature, the authors report a case of myositis ossificans
      of the right pterygoid and temporalis muscles in a patient undergoing surgery to
      remove the left medial pterygoid muscle owing to the same pathology. The
      metachronous localisation in contralateral masticatory muscles compared to the
      primary site leads the authors to emphasize the post-traumatic and iatrogenic
      etiology of this rare pathology. In the light of their experience, they underline
      the importance of a precise diagnosis and surgical exeresis, followed by cautious
      rehabilitation with the least trauma, if necessary backed by appropriate medical
      treatment.

PMID- 9265097
TI  - [Congenital granular-cell epulis. A histochemical case study].
AB  - Following a review of the literature the author reports the various different
      hypotheses regarding the origin and nature of congenital epulis, a pedunculated
      neoformation with a gingival or more rarely mandibular localisation. Epulides
      present dimensions varying from a few millimetres to a couple of centimetres and
      they may exceptionally be multiple in the same subject. A case of granulocellular
      congenital epulis is reported covered by integral mucosa, located in
      correspondence with the maximally gingiva in a paramedical site. The epulis,
      removed a few days after birth since it prevented the child from sucking, did not
      present any other pathological element and underwent optical microscope
      examination using hematoxylin staining, eosin, PAS, argentic impregnation
      according to Gomori, Masson's Trichromic, Alcian Bleu. The results are discussed
      in relation to the histogenesis of this rare gingival lesion: the histogenetic
      question is still unresolved given that even the ultrastructural tests performed
      by various authors have yielded discordant results. The hypothesis of an
      hamartomatous nature of the epulis is however more plausible than the hypothesis
      of a neoplastic process in the strict sense of the term.

PMID- 9265098
TI  - [The efficacy of and tolerance for ketoprofen lysine salt in solution for
      oropharyngeal use in inflammatory lesions of the oral cavity].
AB  - BACKGROUND: A double blind randomized comparative clinical study vs placebo
      clinical study has been carried out in order to assess the antiinflammatory and
      analgesic activity of ketoprofen lysine salt in oropharyngeal solution, in pain
      inflammatory pathologies of odontostomatological nature. METHODS: One hundred and
      twenty patients, aged between 18 and 82 years, were recruited for the purpose and
      assigned at random to treatment with ketoprofen lysine salt or placebo for a
      period of 7 days. RESULTS AND CONCLUSIONS: Treatment with ketoprofen lysine salt
      demonstrated a significantly more marked (p < 0.001) anti-inflammatory effect
      than placebo as regards all variables considered: burning, sensation pain, oedema
      and erythema, and by the 3rd day of treatment led to significant remission of the
      symptomatology. Tolerability of ketoprofen lysine salt was excellent.

PMID- 9265099
TI  - [Indices of treatment needs in orthodontics: the applicability of the DAI (Dental
      Aesthetic Index)].
AB  - The objective assessment of esthetic impairment and relative psychosocial
      handicap for unacceptable dental aspect (useful for characterizing the need of
      treatment), could be satisfied by an index that measures each individual's
      occlusal trait and the psychological impact of the same. An index with these
      characteristics was suggested by Cons and Jenny, already since 1985. This is an
      index (DAI: Dental Aesthetic Index) designed specifically to measure dental
      esthetics, based on esthetic standards socially defined and focused through an
      extensive and finalized search. Therefore this index assesses the social
      acceptability of the dental appearance based on the public perception of dental
      esthetics. The authors, in this work, indicate as measuring the objective traits
      of occlusion and arriving to final score trough simple calculation. This score
      provides severity levels of esthetic, psychologic and functional impairment
      relative to dental aspect in examination.

PMID- 9265100
TI  - Lidocaine-prilocaine cream for pain during circumcision.

PMID- 9265101
TI  - Lidocaine-prilocaine cream for pain during circumcision.

PMID- 9265102
TI  - Lidocaine-prilocaine cream for pain during circumcision.

PMID- 9265103
TI  - Lidocaine-prilocaine cream for pain during circumcision.

PMID- 9265105
TI  - Clonality in Kaposi's sarcoma.

PMID- 9265104
TI  - Clonality in Kaposi's sarcoma.

PMID- 9265106
TI  - Alpha-tocopherol and Alzheimer's disease.

PMID- 9265107
TI  - Alpha-tocopherol and Alzheimer's disease.

PMID- 9265108
TI  - Aortic transection following air-bag deployment.

PMID- 9265109
TI  - Reflex sympathetic dystrophy syndrome following air-bag inflation.

PMID- 9265110
TI  - Traumatic hearing loss following air-bag inflation.

PMID- 9265111
TI  - Not a "bee-zoar," but a wasp.

PMID- 9265113
TI  - Proceedings of the 6th International Congress on Neuronal Ceroid Lipofuscinoses.
      Gustavelund, Finland, 8-11 June 1996.

PMID- 9265112
TI  - Not a "bee-zoar," but a wasp.

PMID- 9265114
TI  - [The physiopathological and therapeutic aspects of esophageal diverticula].
AB  - The authors reviewed 23 surgical cases of symptomatic oesophageal diverticula. In
      Zenker's diverticula (7 cases) the surgical treatment consisted of extramucosal
      cricopharyngeal myotomy and diverticulectomy (6 patients) or diverticulum
      suspension (1 patient). The operations in epiphrenic (15 patients) and mid
      thoracic (1 patient) diverticula were as follows: diverticulectomy, longitudinal
      extramucosal myotomy and antireflux surgery (11 cases); myotomy and antireflux
      surgery (4 cases); myotomy alone (1 patient). There was no operative mortality.
      Postoperative complications occurred in 3 patients (13%). 15 patients were
      followed for an average time of 60 months. None of them developed postoperative
      dysphagia. Pathogenesis, diagnostic methods and surgical options are discussed.

PMID- 9265115
TI  - [Low ileorectal anastomosis in the surgery of ulcerative rectocolitis].
AB  - The authors report their experience of 23 patients with ulcerative colitis
      treated with surgery from 1991 to 1994. At admission 8 patients had a high-grade
      illness, 10 patients had a middle-grade illness, 5 patients had a toxic
      megacolon. All the patients were treated with systemic medical management
      (mesalazine + methylprednisolone) and topical medical management with rectal
      steroid (methylprednisolone) and rectal mesalazine by enema, and with nutritional
      support (Total Parenteral Nutrition). The 5 patients with toxic megacolon, after
      48 hours of unsuccessful medical management, underwent surgery with deferred
      urgency; the other 18 patients underwent surgery after one-four months. The
      authors prefer the ileorectal anastomosis (IRA), since the rectal lesions are
      more susceptible to topical therapy. A single-stage IRA was performed in 17
      patients. A sigmoid resection has been employed in the first stage in the 18th
      patient with a local development of the disease in the sigma; a following relapse
      of the lesions required a total colectomy with a low ileorectal anastomosis. A
      first-stage subtotal colectomy with ileostomy and Hartmann closure of the rectum
      with low ileorectal anastomosis at a later date was performed in the 5 patients
      with toxic megacolon. One of these, 18 years old, died after a heart failure.
      After surgery, as soon as the patients start moving their bowels all of these had
      again a systemic therapy with mesalazine for a short period and after they had a
      topical therapy with mesalazine + methylprednisolone by enema, for a long period.
      The average postoperative period of admission was 16.3 days. The functional
      results have been encouraging with an average of 1.6 bowel movements daily and an
      average of 0.4 nocturnal bowel movements. All the patients had a normal anal
      sphincter function with an acceptable stool frequency. In male patients there no
      urinary or sexual defects. In one case of these, there was a low grade of
      dysplasia, revealed by endoscopic biopsy. The authors conclude that today
      surgical treatment of ulcerative colitis is not well established.

PMID- 9265116
TI  - [The selective use of intraoperative cholangiography in video laparoscopic
      cholecystectomy].
AB  - Intraoperative cholangiography, a diagnostic method through images introduced in
      to clinical use in 1932, has recently become a different technical support from
      that attributed by traditional surgery and it has got a different diagnostic
      meaning with the introduction of video surgery. The authors used it in 54 of 194
      patients submitted to a CVL, always making use of the trans-cystic access, with a
      percentage of success of 82.6%. It was not possible in 8 patients due to the
      complete section of the cystic duct during the work (3 cases) and the
      impossibility of introducing the catheter (5 cases). There is still no common
      agreement about the opportunity to use IC daily: the authors think selective use
      is better preceded by a careful clinical laboratory instrumental preoperative
      study to find patients with the common duct stone. Besides, they are of the
      opinion that a rigorous surgical technique is fundamental to reduce the lesions
      of the VBP that there are not in their experience.

PMID- 9265117
TI  - [The quality of life of the geriatric patient after a surgical intervention. VI.
      Interventions on the biliary tract].
AB  - After reviewing the literature on this subject, the authors examine the quality
      of life of geriatric patients after biliary tract surgery secondary to biliary
      tract carcinoma or non-neoplastic pathologies. From an analysis of the results
      the authors conclude that surgery is useful not only in non-neoplastic forms, but
      also in the event of carcinoma given that it is possible to improve the quality
      of life of these patients.

PMID- 9265118
TI  - [Rare causes of serious digestive hemorrhages].
AB  - The rare causes of massive hemorrhage in the gastrointestinal tract are not
      completely classifiable. They are characterized by high variability, as shown in
      several isolated reports. In our experience of 17 cases, clinical and endoscopic
      features were sometimes typical of a rare pathology, others were referable to
      common pathologies and exactly diagnosed only by angiography or surgery. Our
      experience points out the difficulties in the surgical prescription and timing,
      when the endoscopic diagnosis was lacking or unsure, or when a massive
      haemorrhagic recurrence forced diagnostic laparatomy. The role of endoscopy and
      the advantages of intraoperative enteroscopy have been compellingly demonstrated.
      Diagnostic and therapeutic angiography has been the main method in vascular
      hemorrhage.

PMID- 9265119
TI  - [Abdominal abscesses: their treatment and the study of prognostic factors].
AB  - The aim of this study is to define outcome predictors that might influence the
      prognosis and the mortality rate either of percutaneous drainage (DP) or open
      surgical drainage (DC) for abdominal abscesses. Seventy-one patients with 81
      intra-abdominal abscesses were prospectively studied. They were 40 males and 31
      females. Mean age was 47 +/- 15 years. Thirty-six (50.7%) patients had a simple
      abscess, while 35 (49.2%) had a complex abscess. Abscesses occurred most commonly
      in the sub-hepatic area, pelvic and para-colic space. Thirty-two (45%) patients
      had a percutaneous drainage, while 39 (54.9%) underwent an operative drainage
      management. Criteria for treatment selection were not randomized. However the two
      groups were statistically similar in respect to clinical features, cirrhosis,
      nutritional status, APACHE II scores), genesis and characteristics (simple,
      complex) of the abscesses. The treatment was considered successful when not
      requiring further drainage and the patient survived. Abdominal abscesses were
      cured in 53 (74.6) patients. In 13 cases (18.3%) a further drainage was necessary
      to obtain a complex resolution. Post drainage complications were significantly
      higher in the surgical drainage group (38.4% vs 12%, p < 0.05) because of the
      high incidence of wound infections. The overall mortality rate was 7%. Using an
      univariate analysis model, the only significant variable related to unsuccessful
      outcome in both the percutaneous and surgical group was abscess complexity (p <
      0.005). Elderly (p < 0.005), malnutrition (p < 0.03), presence of cancer (p <
      0.05), a high APACHE II score (p < 0.005) and the presence of a complex abscess
      (p < 0.02) were significantly identified as determinants of death.

PMID- 9265121
TI  - [The Hartmann intervention. The current indications and the authors' own
      experience].
AB  - Seventy years after it was first presented at the 30th Congress of the French
      Association of Surgery Hartmann's operation still fulfils a necessary albeit
      limited role in colorectal surgery. It is generally regarded as necessary in
      emergency surgery when general or local conditions advise against immediate
      anastomosis or would make it dangerous, or more rarely it is used electively in
      palliative neoplastic pathologies. The authors report their personal experience
      over twenty years and the reasons which led them to opt for this technique rather
      than others. Their personal postoperative mortality rate is similar to that
      reported in the literature and is not correlated to surgical trauma but rather to
      the severity of clinical conditions.

PMID- 9265120
TI  - [Fistulectomy with closure by first intention in the treatment of perianal
      fistulae].
AB  - The authors report in a retrospective study their experience in the treatment of
      anal fistulas suggesting the total exercises of the fistula with primary closure
      of external and internal anal sphincters and rectal mucosa. In our department of
      surgery between 1987 and 1993, 36 patients (22 males and 14 females) with anal
      fistulas (17 intersphincteric, 15 trans-sphincteric and suprasphincteric) were
      treated with this technique. Postoperative in-hospital stay ranged between 2 and
      5 days (mean 3.1) and surgical healing needed 12-15 days. A dehiscence of distal
      tract was observed in 3 cases (8.2%). in these cases secondary closure of the
      wound needed 24-28 days. All the patients controlled at follow-up (it lasted at
      least 1 year) did not show rectal incontinence for gas or stools. The authors
      conclude that total exeresis with primary closure is a safe procedure indicated
      in the treatment of anal fistula not associated to inflammatory bowel disease in
      consideration of earlier healing and minor costs.

PMID- 9265122
TI  - [The surgical treatment of hemorrhoids: diathermocoagulation and traditional
      technics. A prospective randomized study].
AB  - INTRODUCTION: The operations to treat hemorrhoids of III and IV degree are
      numerous but classifiable into two groups: "closed" techniques such as Ferguson,
      Parks and Khubchandani, and "open" techniques such as Arnous-Parnaud of the most
      famous Milligan-Morgan. Recently the Anglo-Saxon school was proposed a technical
      variant to Milligan-Morgan operation: it involves diathermy excision without
      peduncle ligature. This technique partly because of the coagulation of the pain
      receptor, partly because of the absence of "at risk" sutures in septic ground
      would involve a reduction in the postoperative pain. We have developed the
      following study to have a global valuation of these methodologies. MATERIALS AND
      METHODS: From November 1993, 135 patients with haemorrhoids of III and IV degree
      have been recruited and grouped in 3 random groups: the patients of the I group
      have been subjected to closed hemorrhoidectomy (Ferguson and is variant according
      to Khubchandani), the patients of the II group have been subjected to the
      Milligan-Morgan operation and those the III group of the diathermy
      hemorrhoidectomy. All the patients have had the same kind of preoperative
      preparation and the same kind of analgesic during the post-operative course.
      Before the operation all the patients were given a questionnaire including a
      scale of the pain on which the administrations of analgesic were also noted.
      RESULTS: A faster canalization and a minor postoperative pain were found in the
      patients of the II and III group and among them a minor use of analgesics in
      those subjected to diathermy-hemorrhoidectomy. No statistical difference occurred
      in postoperative haemorrhage into Milligan-Morgan and diathermy hemorrhoidectomy
      without peduncle ligature (2.2%). CONCLUSIONS: All the methods we have considered
      have turned out to be effective for the clinical and anatomical recovery.
      However, in our experience, the open techniques involve in a significant
      reduction of the postoperative pain and those made with diathermy permit a minor
      use of analgesics in comparison with those made a conventional scissor excision.
      Finally the peduncle ligature doesn't influence postoperative haemorrhage.

PMID- 9265123
TI  - [Combined outpatient surgical-cryotherapeutic treatment of anal fissures. Our
      experience].
AB  - The authors describe their technique and their experience of ambulatory surgical
      cryotherapeutic combined, treatment of anal fissure. The data were observed in 35
      patients (medium age 37.5); in 16 cases, previous treatments gave no benefit. The
      surgical treatment was the lateral internal close sphincterotomy according to
      Notaras, with local anesthesia (personal technique), followed by a fissure
      curettage with a N protosside cryosound. The results confirm the well known
      effectiveness of lateral internal sphincterotomy and the validity of ambulatory
      treatment and of cryotherapy.

PMID- 9265124
TI  - [The surgical treatment of the thoracic recurrences of operated breast cancer].
AB  - Authors report their experience concerning surgical treatment of thoracic
      recurrence from previously operated breast cancer. 96 patients were treated: 9
      with loco-regional chest wall recurrence, 84 with malignant pleural effusion, 3
      with solitary lung metastasis. Eight of 9 cases with chest wall recurrence
      underwent skin and soft tissue "en bloc" resection while in one case a
      thoracectomy was performed. Malignant pleural effusions were treated by
      thoracentesis in 21 cases (25%), tube thoracostomy in 8 (4.76%), tube
      thoracostomy plus chemical pleurodesis in 54 (64.2%) and pleurectomy in one case
      (1.19%). In all the cases with solitary lung metastasis a wedge resection was
      performed. Two out of 9 patients with chest wall recurrence are not evaluable as
      they did not enter the minimum follow-up period (15 months), 6 died after a mean
      period of 18.6 months (range 15-25) following surgery and one is alive at the end
      of the follow-up (39 months). Among the 3 patients with solitary lung metastasis
      2 died respectively 26 and 31 months after procedure and 1 is alive at 28 months.
      Above 54 patients treated by tube thoracostomy plus pleurodesis for malignant
      pleural effusion, 35 showed a complete response, 13 a partial response and 6 were
      non-responders. No postoperative complications were observed in the patient who
      underwent pleurectomy while an almost complete resolution of the pain was
      achieved.

PMID- 9265125
TI  - [The current indications for Madden's radical mastectomy in our experience. A
      critical review of 201 consecutive patients].
AB  - The clinical pathological data regarding the 201 patients (203 operations
      running) who underwent radical mastectomy according to Madden in the II Division
      of General Surgery at Brescia Civil Hospital in the period 1993-1994, have been
      reexamined in order to check the real need of radical surgery. This further
      analysis, apart from the patients with neoplasias of considerable dimensions (T2;
      > 2 cm), has been carried out on 100 tumors smaller dimensions (T1; < 2 cm) and
      has confirmed the necessity of radical surgery in 87 cases. Of the 13 operations
      (6.4%) that have been considered "improper" 2 were due to erroneous clinical
      staging (dubious cutaneous infiltration) and 5 (2.5%) presented a neoplastic
      diameter of exactly 2 cm which only partially justified radical surgery. In six
      patients (2.9%) we haven't found clinical pathological elements which
      contraindicated conservative surgery.

PMID- 9265126
TI  - [The evolutionary principles of inguinal hernioplasty through our personal
      experience].
AB  - Inguinal hernia is a multi-factorial pathologic condition. A constitutional
      weakness of transversalis fascia, probably genetically transmitted, represents a
      fundamental cause. Hernioplasty has evolved year by year from the "Bassini" to
      the "tension-free" techniques with Marlex or Prolene prosthesis, on the rational
      base of no tension on constitutionally weak structures. The data reported
      confirmed the absolute validity of "tension-free" hernioplasty.

PMID- 9265128
TI  - [The role of imaging diagnosis in the study of thyroid neoplasms].
AB  - The aim of this paper was to evaluate the role of imaging techniques and methods
      in the diagnosis of thyroid tumours. The main aim was to analyse the various
      imaging methods and to search for an integrated diagnosis based on clinical and
      laboratory evaluations and techniques such as fine needle aspiration biopsy for
      which imaging is used as a guide. The authors stress the importance of analysing
      the sensitivity of the various methods in preoperative staging. The methods
      examined here include: scintigraphy, ultrasound, fine needle aspiration biopsy,
      Doppler ultrasound, color-Doppler scan, TC and magnetic resonance.

PMID- 9265127
TI  - [The type of local treatment conditions the prognosis in patients with
      nonmetastatic Ewing's sarcoma of the extremities treated with adjuvant
      chemotherapy].
AB  - The results obtained in 172 cases of non metastatic Ewing's sarcoma of the
      extremities are reported. The patients were advised to undergo surgical
      treatment, followed by radiotherapy (40-45 Gy) in case of inadequate surgical
      margins. 48 patients who refused surgical treatment, were locally treated with
      radiotherapy alone (50-65 Gy). With a mean follow-up of 8 years (R. 3-15) 101
      patients (58.7%) are free of disease and 68 relapsed with metastases and/or local
      recurrence. A radio-induced bone sarcoma developed in two patients, one patient
      died of ADM cardiomyopathy. No differences in terms of risk factors were observed
      between patients who were or were not treated with surgery. A better DFS was
      observed in the patients treated with surgery (66.9%) in comparison with those
      treated with radiotherapy alone. The higher percentage of local recurrences
      observed in patients treated with radiotherapy alone seems to be responsible for
      the worse prognosis observed in these patients. The authors' conclusion is that
      the local control in patients with non metastatic Ewing's sarcoma should always
      be achieved by means of surgery.

PMID- 9265129
TI  - [A case of primary hepatic carcinoid. A report of its surgical resolution].
AB  - Primary hepatic carcinoid tumors are extremely rare; conversely, the liver is the
      most frequent site of metastases from gastrointestinal carcinoids. Clinically,
      primary lesions are characterized, in most cases, by the absence of an overt
      endocrine syndrome. Histologic findings and immunohistochemical demonstrations of
      chromogranin and neuron specific enolase, generally, enable the neuroendocrine
      origin of these neoplasms to be established. Prognosis after surgical treatment
      of primary hepatic carcinoids seems to be more favorable when compared with other
      hepatic carcinomas.

PMID- 9265130
TI  - [Biliodigestive fistulae. Apropos 2 cases with opposite symptomatology].
AB  - Biliodigestive fistulas are the most frequent internal biliary fistulas and occur
      when a calculus or neoplasia perforates the wall of the biliary tract of
      intestine at any point. Symptoms vary given that completely asymptomatic cases
      have been reported in which the findings of a biliodigestive fistula was
      completely coincidental, but there are also cases in which the severe clinical
      conditions at onset require immediate surgery. The Authors report two cases with
      opposing symptoms and underline the importance of diagnostic imaging in the
      preoperative analysis. They also underline that a correct therapeutic approach is
      fundamentally important in these cases.

PMID- 9265131
TI  - [Cystic dilatation of the choledochus associated with stenosis of the hepatic
      duct bifurcation. An analysis of a clinical case].
AB  - The authors report a case of cystic dilatation of the choledochus associated with
      narrow stenosis at the confluence of the left and right hepatic ducts which was
      found to be inflammatory on histological examination. This pathology is becoming
      an increasingly more commonplace clinical finding. The case reported here is
      particularly interesting owing to the onset of the disease and the way in which
      it was treated. An attempt was made to treat the patient using a simple operation
      which was to the least radical possible. The authors take this opportunity of
      reviewing the literature on the subject.

PMID- 9265133
TI  - [A large symptomatic gastric leiomyoma. A case report and considerations of the
      treatment possibilities].
AB  - The authors describe the case of a female patient affected with large symptomatic
      gastric leiomyoma, six centimeters in diameter, who presented to clinical
      observation referring gastric pain and melena. The first gastroscopy showed
      massive bleeding from a submucosal gastric lesion. The lesion was not
      endoscopically resectable and the injective endoscopic treatment of bleeding
      failed. The patient was surgically treated with laparotomic excision of the
      leiomyoma. She was back home in ten days. The authors describe this case to
      discuss the possibility to resect large gastric leiomyomas using endoscopic
      resection indeed surgical approach. They also enhance the validity of surgical
      treatment for its safety and radical approach to large lesions.

PMID- 9265132
TI  - [The superior vena cava occlusion syndrome. A case of neoplastic thrombosis due
      to hepatocarcinoma and cirrhosis].
AB  - The authors report their experience with 11 patients, surgically treated since
      1990, affected with superior vena cava syndrome. A peculiar case of neoplastic
      thrombosis in hepatocarcinoma is stressed. In fact a similar case hadn't been
      reported in the last ten-year literature, although hepatocarcinoma may spread in
      different organs. A subject review and a discussion are presented.

PMID- 9265134
TI  - [Cystic adenomatoid malformation of the lung in an adult].
AB  - Congenital cystic adenomatoid malformation of the lung (CCAM) is characterized by
      an adenomatoid proliferation of bronchiole-like structures and cysts formation.
      The condition is most commonly found in newborns and children and it may be
      associated with other malformations; rarely, the presentation is delayed until
      adulthood. This paper presents a case of CCAM in a 62-year-old male, who
      presented with recurrent bacterial pneumonias and breathlessness one exertion.
      The chest X-rays and CT scan revealed a patchy opacity in the right lower
      pulmonary zone. Bronchoscopic examination was normal. At surgery, a mass
      involving the right lower and middle lobes, and enlargement of hilar lymph nodes
      were found. A bilobectomy was performed without complications. Examination of the
      gross specimen showed a lesion characterised by multiple small cysts, all less
      than 1 cm in diameter; they were lined predominately by columnar epithelium,
      occasionally by ciliated epithelium. Rare cysts were lined by foreign body giant
      cells. Elastic fibers and smooth muscle were present within the cysts wall.
      Peripherally, there were normal alveoli and bronchioli mixed with cysts, and
      plasmalymphocytic infiltrates. The final diagnosis was Stocker's Type II CCAM of
      the lung. CCAM of the lung is a rare development lesion of the lung and it has no
      sexual predilection. It is usually unilateral and sublobar or lobar in size, but
      occasionally it can be multilobar. Typical histologic feature of CCAM are
      adenomatoid proliferation of bronchiole-like structures and macro- or microcysts
      lined by columnar or cuboidal epithelium and absence of cartilage and bronchial
      glands. Inflammatory changes are not found in infants, but may be present in
      adult patients. Based on the size of the cysts, CCAM may be classified into three
      different types: type I characterised by multiple cysts, over than 1 cm in
      diameter; type II with smaller cysts, less than 1 cm in diameter; type III that
      shows solid lesions composed of bronchiole-like structures. Type II is commonly
      found in childhood, but is occasionally seen in adult patients, as that one in
      our report. The insult probably occurs between 4th and 7th week of fetal life.
      The etiologic agent is unknown. The histologic diagnosis of CCAM is difficult in
      adult patient, perhaps because of supervening infections that sometimes distort
      the underlying diagnostic pathologic appearances and make them difficult to
      recognise, as happened in our case. From the clinical point of view, most of the
      lesions cause severe respiratory failure; in adult individuals the diagnosis is
      difficult, since there are very few relevant symptoms and signs. The patients can
      present with fever, recurrent infections, breathlessness and haemoptysis. The
      chest X-rays abnormalities are not specific and include homogeneous or
      multicystic opacities. Similarly, other diagnostic methods add no further useful
      informations. Surgical treatment is necessary also in adult patients, because of
      the risk of recurrent pulmonary infections and malignancies associated with CCAM.
      Lobectomy is the treatment of choice, but sometimes a larger resection is
      required, when the lesion involves more than one lobe.

PMID- 9265135
TI  - [Medullary carcinoma of the thyroid. A report of 4 clinical cases and a review of
      the literature].
AB  - Medullary thyroid carcinoma is an uncommon neoplasia among other differentiated
      carcinomas or the thyroid gland. We have retrospectively analysed four new cases
      of medullary thyroid carcinoma and a careful review or the literature on the
      subject has been conducted.

PMID- 9265136
TI  - [Hemolysis and multiple trauma. A clinical case report].
AB  - A patient is described who presented hemolysis after a chest and head trauma. We
      checked out every possible cause of anemia and our conclusion is that trauma
      itself was the cause of hemolysis. As an explanation, we suggest that red blood
      cells were broken in lung capillaries because of endothelial damage due to
      pulmonary injury.

PMID- 9265137
TI  - [The "pedrada" ("coup-de-fouet") syndrome. A possibility to be considered in
      acute leg pain].
AB  - The authors describe a clinical case of pedrada syndrome in a patient formerly
      suffering from acute CID. It is a pathology enough rare and easily mistakable
      with phlebotrombosis of leg but from which is well to be able to do differential
      diagnosis because of therapy for an affection is clearly contraindicated for the
      other.

PMID- 9265138
TI  - [Retroperitoneal hematoma during heparin therapy. Comments on 3 cases].
AB  - The authors review the literature during the past ten years relating to the onset
      of retroperitoneal hemorrhage during heparin treatment. The phenomenon may be
      attributed to a thrombotic genesis involving the adrenal glands and may or may
      not be correlated to the presence of heparin-induced immune phenomena. The
      severity of the phenomenon is readily understood: given that the pathology is
      heparin-dependent, suspension of heparin treatment is the first main step to be
      taken; this is evidently a cause of risk in relation to the pathology that
      imposes the use of heparin. The rarity of this complication means that, according
      to the authors, it has been undervalued. They report three cases which were
      brought to their attention over the past three years. On the basis of their
      experience, the authors underline the importance of knowing the causes that are
      supposed to be responsible for the complication and the study of blood
      coagulative status. In order not to overlook the possible adrenal genesis of the
      phenomenon they also recommend a careful exploration of the adrenal glands when
      faced with a retroperitoneal hematoma in which the source of hemorrhage cannot be
      identified.

PMID- 9265139
TI  - [Access to the rectum via a posterior route and via a combined abdominal
      posterior route: when and why].
AB  - The authors report their experience of the posterior rectal access route. They
      used this route to operate 7 patients with rectal carcinoma during the period
      February 1989-October 1994; 3 patients were affected by villous adenoma, 3 by
      adenocarcinoma, and 1 by pelvic recidivation. Of the 3 patients suffering from
      adenocarcinoma, two underwent palliative treatment owing to their poor general
      conditions and the systemic nature of the base pathology, consisting in the
      exeresis of the tumour using a posterior route. The third patient was treated
      using a combined abdominal-posterior route; the site of the tumour and the
      presence of a narrow pelvis would in fact have made an "ultra low" front
      resection highly risky, whereas coloanal anastomosis (pull through) might have
      jeopardized efficacious anal continence. On the basis of their experience the
      authors indicate the posterior access route as a therapeutic possibility in the
      treatment of medium-low rectal tumours at an early or very advanced stage. The
      posterior approach is only justified in other forms if combined with laparotomic
      access. An oncologically correct operation is therefore guaranteed in full
      respect of sphincteric function.

PMID- 9265140
TI  - [The treatment of bronchopleural fistulae due to bronchial dehiscence by chest
      wall interventions. The authors' personal experience].
AB  - The authors present their personal experience of three cases of bronchial
      fistulae post pneumonectomy or lobectomy. Surgical treatment was not done
      directly on the bronchial stump but by thoracoplasty. This approach to the
      thoracic chest gets good results on condition that stabilization in reexpansion
      of residual parenchyma and drainage of bronchial secretions is carried out.

PMID- 9265141
TI  - [Local anesthesia in the surgery of inguinal hernia. Technical notes].
AB  - Routine use of local anaesthesia associated with tension-free hernioplasty in
      surgical treatment of inguinal hernia allows an immediate patient walking and
      prompt discharge from the hospital unit: with this technique 89 cases in two
      years were operated. The anaesthesia-related discomforts and complications are
      minimal. The addition of an intravenous sedative (propofol) premis to extend this
      approach to anxious patients too.

PMID- 9265142
TI  - [Prevalence and risk factors in diffuse idiopathic skeletal hyperostosis in a
      population sample in Hungary].
AB  - The aim of the study was to get some information on the epidemiology and etiology
      of DISH which is a frequent, chronic, benign musculoskeletal disease. In order to
      investigate the epidemiology of DISH the authors planned a population-based cross
      sectional study and to investigate the etiology of the disease they planned a
      case-control study. The prevalence of DISH in Hungary in men over the age of 50
      years is 5.8% and in women is 1.3%. In men DISH begins earlier in the lifetime
      and over the age of 65 years the prevalence increases rapidly in both sexes. In
      men throughout the life the disease is more common and more severe than in women.
      In the case-control study the authors investigated the association of the disease
      with risk factors as obesity, hyperuricemia, hypercholesterinemia,
      hypertriglyceridemia. Hyperuricemia was significantly more frequently found in
      DISH than in the control group. In the name of DISH the word "idiopathic" is
      questionable because apart from the known glucose metabolic imbalance other
      metabolic abnormalities (uric acid) could be found. There might be a complex
      metabolic disturbance in the etiology of DISH.

PMID- 9265143
TI  - [Polymorphism of the 52 triplet gene (nucleotide 253) of the TSH receptor in
      Basedow-Graves patients and in healthy controls].
AB  - It has been analysed the polymorphism of the first exon of TSH receptor gene, at
      the first nucleotide of the triplet 52 of the genomic DNA (CCC/ACC, Pro/Thr) in
      Graves' disease and control population and was not found connection between the
      genetic background, clinical picture and some immunological parameters. Genomic
      DNA was obtained from formalin-fixed, paraffin embedded thyroid tissue of
      patients with Graves' disease underwent subtotal thyroidectomy and from
      peripheral blood leukocytes. The first exon and small part of the first intron of
      the TSH-R gene was amplified by PCR. The motif was amplified by the primers and
      primers includes restriction site of the Tth 111 I restriction enzyme and mutant
      form of the examined nucleotide. Genomic DNA having only wild allele was detected
      at 189 bp, while mutant allele was digested a 167 and a 22 bp fragments. Three
      persons (two female and one male) of the 32 patients with Graves' disease had
      mutation A253 in heterozygotic form: The patient with mutation A253 had no any
      symptoms of Graves' ophthalmopathy. No correlation was found between mutation
      A253 and the levels of anti-TSH-R-, anti TG, anti-TPO and anti-eye muscle
      antibodies. Surprisingly, it was found mutation of heterozygous genotype in two
      control individuals (one female and one male) of 14 without any symptoms of
      thyroid disease and negative laboratory findings. Finally, it has not been found
      the association of the 253 nucleotide of the codon 52 polymorphism with Graves'
      disease and ophthalmopathy and the allele A253 has no pathogenetic relevance in
      Graves' disease. On the other hand, it cannot be excluded that other mutation or
      sequence polymorphism in the remainder of TSH-R extracellular domain might be
      important in autoimmune mechanism of Graves' disease.

PMID- 9265144
TI  - [Some aspects of the use of prostaglandin E1 in cases of erectile dysfunction].
AB  - The author reports about his first experience of the use of prostaglandin E1
      (PGE1) for the treatment of the erectile dysfunction. Results and observations of
      the self injection treatment with PGE1 of 46 patients are reported. Main
      indications and some practical aspects of the use of PGE1 are discussed after 5
      short case reports. Upon the international experience and his own first results
      the authors opinion is, that the PGE1 is especially useful for the self injection
      treatment of the erectile dysfunction because of its rare complication rate.

PMID- 9265145
TI  - [Ethical questions concerning organ transplantation, with special reference to
      Great Britain].
AB  - Although the cousience and character of a good doctor are sufficient on their own
      to allow us to discuss and make decisions regarding very difficult ethical
      subjects in transplantation, basic ethical principles commonly used in medicine
      must also be applied to various aspects of organ donation. Some system has to be
      adopted that assesses the weight that must be given to various possible
      solutions. For example, would live donor transplantation still be acceptable if
      there were a surfeit of cadaveric organs? If animal organs can be transplanted
      successfully, is that more desirable than using human organs: particularly if
      human donation involves interventional ventilation or non-heart beating donors?
      Is interventional ventilation more "ethical" than live donor liver or lung
      transplantation? No doubt future developments in transplantation, opening more
      opportunities for the successful treatment of more patients, are likely to
      produce increasingly difficult ethical issues. Discussions of these issues must
      be firmly based on principles of medical ethics, although accepting that whilst
      absolute principles may be available, absolute answers are more difficult to come
      by.

PMID- 9265146
TI  - [A case of myelodysplastic syndrome transforming into acute B-cell lymphoid
      leukemia].
AB  - Case history of a seventy year old man with myelodysplastic syndrome is
      presented. The disease terminated into acute leukaemia in 22 months. The pure, B
      lymphoid stem cell nature of the leukaemic cells has been proved, beside
      morphology and cytochemistry, by detailed flow cytometric phenotyping and PCR
      amplification as well as sequencing of the immunoglobulin heavy chain gene CDR3
      region.

PMID- 9265147
TI  - [Gastroenterologic sub-acute care unit at the hospital department of internal
      medicine letter)].

PMID- 9265148
TI  - [The importance of a sub-intensive care unit in gastroenterology].

PMID- 9265149
TI  - [Glucocorticosteroids and ambroxol inhibit secretion of inflammatory cytokines in
      tracheobronchial epithelial cells: Possible role of the NF-kappa B transcription
      factor].

PMID- 9265150
TI  - [Tracheal normal mucin secretion and morphology and after SO2 and NO2-induced
      tracheobronchitis in the rat model].

PMID- 9265152
TI  - [Pulmonary melioidosis in a German Southeast Asia tourist].
AB  - HISTORY AND CLINICAL FINDINGS: A patient who returned from a 3-year stay in
      Thailand and India one year ago, was admitted with fever of 38.5 degrees C and
      productive cough for the last four weeks. He remembered wounding his foot three
      years ago in India with contamination by soil. Subsequently, recurrent pustulae
      appeared on his feet. One such pustule was found on admittance. The clinical
      examination showed low body weight, without further abnormalities.
      INVESTIGATIONS: The blood examinations revealed high inflammation parameters and
      ruled out any immunodeficiency. Smouldering infiltrates in the upper lobes were
      found on the chest radiography. Sputum was free of acid fast bacilli and no
      mycobacterial DNA was detected by polymerase chain reaction. Bronchoscopy showed
      a normal endobronchal situation, Burkholderia pseudomallei were found to grow
      from specimens of bronchial mucus. TREATMENT AND COURSE: Under the empirical
      treatment with ampicillin/sulbactam, we could not find any response. After
      switching to Ceftazidime and trimethoprim/sulfamethoxazol (TMP/SMZ) we observed
      quick clinical improvement and normalisation of the inflammation parameters and
      notable radiological response over three weeks. We continued a five months
      TMP/SMZ therapy after discharge in order to prevent relapses. CONCLUSION: For
      travellers and immigrants from Southeast Asia presenting smouldering
      infiltrations of the upper lobes, one should include Melioidosis in the
      differential diagnosis.

PMID- 9265151
TI  - [Hypoxia and inflammation--causes of acute and chronic pulmonary artery
      hypertension].

PMID- 9265153
TI  - [Chlamydia pneumoniae pneumonia in hospitalized patients. Clinical
      characteristics and diagnostic value of polymerase chain reaction detection in
      bronchoalveolar lavage].

PMID- 9265154
TI  - [A mutation in the interferon-gamma receptor and susceptibility to mycobacterial
      infections].

PMID- 9265155
TI  - [Effect of the beta-2 mimetic drug terbutaline of growth hormone secretion in
      prepubertal asthmatic children].
AB  - Asthmatics display a tendency to retarded growth and hyposomia in childhood. The
      reasons for this are not yet clear, although the atopic disposition seems to
      occupy a key role. It is a known fact that stimulation of the beta-2 receptors
      results in inhibiting growth hormone secretion. The purpose of our study was to
      find out whether the beta-2 mimetic terbutalin, often used in asthma therapy,
      exercises a negative influence on the spontaneous release of growth hormone in
      children suffering from asthma. The growth hormone release was studied in 10
      prepuberal children suffering from atopic asthma who received intravenous
      therapeutic doses of terbutalin: testing was done for a total period of 24 hours
      before and during administration. Terbutalin effected significant inhibition of
      growth hormone secretion merely during the waking phase (6.2 +/- 1.0 to 3.7 +/-
      0.7 ng/ml), but not during the sleep phase (13.1 +/- 1.8 to 12.5 +/- 2.0 ng/ml)
      and the 24-hour period (11.0 +/- 1.0 to 9.8 +/- 1.5 ng/ml). There was also no
      significant influence on the average group value for the maximum growth hormone
      peak (40.8 +/- 9.5 to 42.7 +/- 11.0 ng/ml). These results point to a short-term
      inhibition of growth hormone secretion, exercised by intravenously administered
      terbutalin. Terbutalin does not seem to be responsible for any clinically
      relevant inhibition of growth and development.

PMID- 9265156
TI  - [Control of training intensity in rehabilitation of chronic obstructive
      respiratory tract diseases].

PMID- 9265157
TI  - [Inpatient pneumologic rehabilitation of adults: goals--diagnostic and
      therapeutic standards--research needs].

PMID- 9265158
TI  - [Meta-analysis of respiratory rehabilitation in chronic obstructive pulmonary
      disease].

PMID- 9265159
TI  - [Lung transplantation in lymphangioleiomyomatosis].

PMID- 9265161
TI  - [Nontraditional methods for prevention of recurrent tuberculosis].
AB  - A follow-up of 36,323 patients with clinically cured tuberculosis in 1981-1990
      revealed that of them 1866 (5.1%) had a recurrence. The prediction method by
      systematic mathematical statistics permitted the division of patients into high
      and low risk groups. If a sum of diagnostic ratings (DR) exceeded +19.7, these
      patients comprised a high risk group and if the sum was below -6.3, the patients
      were a low risk group. When the sum was between these figures, the patients
      needed additional immunogenetic examination and determination of gene locuses in
      the ABCD system; detection of B15, B35, and DR2 indicated a high risk for
      recurrent tuberculosis, that A19 and DR3 showed its low risk. Additional
      antituberculosis measures prevented the occurrence of a recurrent specific
      process.

PMID- 9265160
TI  - [Use of data bank on tuberculosis patients and of computer program for clinical
      and immunological analysis].
AB  - Three hundred and twenty patients with pulmonary tuberculosis were clinically and
      immunologically compared. The findings support the significance and prospects for
      using a personal computer while making clinical and laboratory comparisons in
      different groups of patients for a prompt and objective analysis of available
      data. Comparative evaluation of the informative value of immunologic tests have
      indicated that in relation to the major clinical parameters of a tuberculous
      process, differences are great in those characterizing both T- and B-cell, and
      specific antimycobacterial immunity. The clinical and immunological findings
      regarding the specific features of a tuberculosis process may serve as the basis
      for multidimensional analysis and development of criteria for computer-aided
      clinical and immunological diagnosis of tuberculosis.

PMID- 9265162
TI  - [Generalized tuberculosis].
AB  - Among all types, generalized tuberculosis has become recently a rather common
      disease. During 10 years, twenty two patients with tuberculous process
      generalization have been identified. Of them 12 had hematogenous tuberculosis, 7
      had infiltrative tuberculosis, 2 had fibrocavernous tuberculosis, and 1 had
      abdominal tuberculosis. Despite the treatment performed, 11 of 22 patients died.
      Among all treatments, surgical interventions play a significant role.

PMID- 9265163
TI  - [Specific antitubercular immunity in patients with tuberculosis and other
      pulmonary abnormality: diagnostic value of its study].
AB  - A hundred and seventy one patients with revealed rounded lung formations of
      tuberculous and non-tuberculous origins were examined. Mycobacterial antigens,
      cellular antituberculosis immunity, and antituberculosis antigens were
      determined. Cellular sensitization to mycobacterial antigens was found to develop
      in about 50% of patients with round lung formations of tuberculous origin. This
      sensitization to PPD was more revealed by BTR rather than by TMR. At the same
      time, the latter is positive in healthy donors and in patients with non
      tuberculous abnormality. Finally it can be concluded that cell tests are little
      suitable for immunodiagnosis of tuberculosis. It was also ascertained that
      determination of antituberculosis antigens and antigenemia might be a important
      component of examinations of patients with rounded lung formations in order to
      make a differential diagnosis of tuberculosis and non-tuberculous abnormality as
      with their determination, high sensitivity and specificity of appropriate tests
      can be achieved. These tests are more informative for the immunodiagnosis of
      tuberculosis than that of infiltrative tuberculosis.

PMID- 9265164
TI  - [Role of external laser radiation in the multimodality treatment of patients with
      destructive pulmonary tuberculosis].
AB  - Patients with destructive pulmonary tuberculosis were examined. Comparing those
      receiving chemopathogenetic, epicutaneous laser and ultrasound therapies showed
      an increase in the incidence of cavitary scarring in those taking successive
      epicutaneous laser and ultrasound therapies and exposed to biologically active
      points. Epicutaneous laser therapy promoted cicatrization of large cavities.

PMID- 9265165
TI  - [Diagnostic features of primary and secondary pulmonary tuberculosis].
AB  - Comprehensive clinical, X-ray, and laboratory studies were made of 495 patients
      with primary pulmonary tuberculosis and 250 with secondary tuberculosis. The
      patients' age was 18 years. Age-specific, clinical, X-ray, microbiological,
      immunological, and metabolic features of the disease were revealed in relation to
      its genesis. It was found that it was difficult to make a diagnosis in primary
      tuberculosis more frequently and to define the intensity of the disease in
      secondary tuberculosis. Sputum tests for bacterial and altered forms of
      Mycobacterium tuberculosis enhanced the verification of primary tuberculosis by
      16% and secondary tuberculosis by 29%. Immunological and biochemical studies used
      in clinical and X-ray examinations permit the increase in the detection rate of
      primary and secondary tuberculosis from 41.7 to 79.6% and from 37.6 to 81.4%,
      respectively.

PMID- 9265166
TI  - [Ways of optimizing the diagnosis and differential diagnosis of ocular
      tuberculosis].
AB  - The results of differential diagnostic study of 1035 patients with actual or
      suspected ocular tuberculosis in different aspects are analyzed. To define the
      diagnostic value of different signs, their comparative assessment was made via
      determination of the validity and informative value. Comparison of the findings
      with the efficiency of antituberculous therapy. In late posttherapeutical periods
      in particular was a reference for verification of the tuberculous etiology of eye
      diseases. There was strong evidence for the use of higher doses of tuberculin for
      diagnostic purposes due to its lower sensitivity. Focal tuberculin reactions were
      ascertained to be of no strict specificity and, if they were slightly pronounced,
      low informative value. The signs of the body's infection to tuberculin and of its
      sensitization were shown to suggest that the eye diseases might be of tuberculous
      etiology. A procedure for its verification was developed, based on the detection
      of specific ophthalmological picture, moderate or great focal tuberculin
      reactions by the type of inflammation and positive testing therapy with
      antituberculous agents. A programme (a system) of differentially diagnostic
      examination and an algorithm scheme aiding a physician to make a diagnosis and
      substantially reducing the frequency of misdiagnoses were proposed.

PMID- 9265167
TI  - [Diagnosis of tuberculosis of the large bronchi by different bronchoscopies].
AB  - Tuberculosis of the large bronchi (TLB) was diagnosed by rigid bronchoscopy (RBS)
      in 9.4% and by fibrobronchoscopy (FBS) in 18.3% of patients. Such great
      differences are attributable to the extension of a visualization area during FBS
      than during RBS. Analyzing the specimens obtained at bronchoalveolar lavage and
      other types of biopsy of TLB areas cytologically and histologically confirmed the
      visual picture in 63.4% of cases.

PMID- 9265168
TI  - [Pulmonary elastic pressure as an indicator of lung tissue morpho-functional
      restructure].
AB  - The examination of 100 patients with tuberculosis and exogenous allergic
      alveolitis showed it expedient to study pulmonary elastic pressure in patients
      without or with or X-ray signs of pneumosclerosis and pulmonary emphysema. Its
      exploration could diagnose initial (pre-X-ray) manifestations of pneumosclerosis
      and pulmonary emphysema in the former patients and specify the extent and
      relatively significant manifestations of these abnormalities at the subsequent (X
      ray detected) stages in the others.

PMID- 9265169
TI  - [Pulmonary hypertension and myocardial contraction in disseminated types of
      pulmonary tuberculosis].
AB  - To elucidate the influence of hemodynamic factors on the development of right
      ventricular failure, hemodynamic parameters of the lesser and greater
      circulations and those characterizing myocardial contractility were studied in 36
      patients. Despite profuse lung damage, pulmonary failure, and marked external
      respiration dysfunction that accompanied disseminated pulmonary tuberculosis,
      pulmonary hypertension was moderate and failed to be followed by hemodynamic
      overload, right cardiac hypertrophy and dilatation. Significant reductions in
      myocardial contractility both of the right and left cavities with a rise in the
      intensity of an inflammatory process suggest the leading role of a toxic and
      infectious agent in myocardial damage.

PMID- 9265170
TI  - [Immediate and late outcomes of surgical treatment in patients with tumor
      simulating pulmonary tuberculosis].
AB  - The specific features and outcomes of surgical treatment were analyzed in 122
      newly detected patients with pulmonary tuberculomas without prior specific
      therapy. Postoperative complications developed in 4.1% of the patients undergone
      surgery, recurrent tuberculosis was observed in 1.6%. Early surgical
      interventions in this group of patients were found to reduce the time of
      treatment and working rehabilitation. A value of intraoperative rapid cytological
      verification of diagnosis was shown while choosing the adequate volume of lung
      resection in difficult diagnostic cases.

PMID- 9265171
TI  - [Tuberculosis infection among teenagers].
AB  - Infection with tuberculosis was studied in 3509 adolescents aged 15 years from
      various social groups via twice BCG revaccination by analyzing the responses to
      Mantoux tests with 2 TU of tuberculin purified protein derivative and by
      following them up for 3 years with an annual examination of the same group. The
      rates of infection among the teenagers was found to be 32.1% and higher (58.5%)
      in persons without vaccination signs, but with the latter they depend upon the
      time after BCG vaccination: 0.7% 3 years after the second revaccination, 30.2%
      after the first revaccination, and 66.8% 15 years following the first
      vaccination. The timely and qualitative antituberculosis immunization during
      twice revaccination contributes to reduced infection rates among teenagers.

PMID- 9265172
TI  - [Endobronchial use of low-frequency ultrasound and ultraviolet laser radiation in
      the complex treatment of patients with suppurative bronchial diseases].
AB  - The efficiency of endobronchial therapy with low-frequency ultrasound (LFUS) and
      ultraviolet laser radiation (UVLR) were studied in patients with pyoinflammatory
      diseases of the lung. A hundred and sixty two patients with chronic bronchitis
      (CB) and bronchoectatic disease (BD) were clinically followed up. The complex
      treatment of pyoinflammatory diseases of the bronchi was supplemented by
      endobronchial LFUS in 86 patients, by UVLR in 29. Routine bronchoscopy (without
      endobronchial application of LFUS and UVLR) was included into the treatment of 47
      patients with CB and BD. Bronchoscopy with LFUS and UVLR was found to have a high
      efficiency in patients unresponsive to drug therapy. The number of bronchoscopies
      per treatment regimen could be reduced, the time of a remission and the interval
      of hospitalization were increased.

PMID- 9265173
TI  - [Intravascular coagulation as a typical concomitant of acute pulmonary
      tuberculosis].
AB  - Hemostasis and fibrinolysis, markers of intravascular coagulation (IC),
      hemorrhagic parameters, and platelet aggregatory properties were studied in 119
      patients with various types of pulmonary tuberculosis. In patients with active
      pulmonary tuberculosis, IC was found to be a persistent and important component
      of a pathological process which both plasma factors and circulating cells were
      involved in. In most critical patients, the degree and rate of spontaneous and
      stimulated platelet aggregation were decreased, when stimulated, the rate of
      increases in the mean volume of aggregates was yet higher in these patients than
      in the controls. The latter created an additional prerequisite for progression of
      microthrombogenesis.

PMID- 9265174
TI  - [Intravascular activation of hemostatic system and DIC syndrome in pulmonary
      tuberculosis].
AB  - The paper summarizes his own findings and literature data on the status of the
      hemostatic system in patients with pulmonary tuberculosis. It discusses various
      terms used to designate intravascular coagulation and variants of this process in
      patients with tuberculosis.

PMID- 9265175
TI  - [Impact of mycobacteria on nonspecific protective mechanisms associated with
      exchange of organic sulphur and nitrogen].
AB  - Guinea-pig experiments indicated that Mycobacteria tuberculosis (MBT) were
      actively involved in detoxification of the xenobiotics polycyclic aromatic
      hydrocarbons (PAH) and substantially altered the nonspecific protective
      mechanisms associated with activation of the body's antioxidative resources. MBT
      in the lung and liver tissues of animals long preexposed to PAH elevated the
      concentrations of sulphur-containing amino acids and glutathione with consumption
      of abundant nitrogen-rich adaptogenic antioxidants (arginine, urea) accumulated
      under the action of PAH. At the same time there is a upward trend for the body's
      antioxidative potentials both in a group infected with MBT and in group receiving
      PAH. Supplementing sodium glutamate potentiated the revealed adaptive
      rearrangements.

PMID- 9265176
TI  - [Role of glutathione containing amino acids in the correction of body's
      dysadaptation states].
AB  - Based on his own experimental findings and data available in the literature, the
      author provides evidence for the expediency of using glutamate alone and in
      combination with glycine and methionine to correct abnormalities accompanied by
      hypoxia and imbalance between the rate of free radical oxidation and the degree
      of antioxidative defense. Pathogenetic therapy with the adaptogens amino acids in
      combination with polycyclic aromatic hydrocarbons is considered.

PMID- 9265178
TI  - [Serum lipids in pulmonary tuberculosis patients with various types of diabetes
      mellitus].
AB  - In 12 patients with pulmonary tuberculosis and in 14 with the disease concurrent
      with types I and II diabetes mellitus, a somatotype was determined and lipid
      metabolism was studied by the blood levels of various lipid fractions, by the
      fractional composition of lipoproteins and atherogenicity coefficient. Lipid
      metabolic changes in patients with tuberculosis and in those with the accompanied
      abnormality were not found to depend upon sex, age, somatotype and the type of
      tuberculosis, but are apparently related with the severity of tuberculous
      intoxication. In the concurrent disease, lipid metabolic changes depended on the
      type of diabetes.

PMID- 9265177
TI  - [Biochemical changes in tuberculosis patients with different somatic types].
AB  - In 100 patients with various types of pulmonary tuberculosis who were residents
      in Eastern Siberia, somatic types and glucose postload sugar curves and
      immunological status were studied and the findings were compared with the
      specific features of the process and its dynamics during chemotherapy.
      Thoracomuscular and thoracogracial somatic types were found in two thirds of
      cases among patients with pulmonary tuberculosis. Persons with these somatic
      types developed chiefly infiltrative tuberculosis. Uncorrectable abnormalities in
      the sugar curves were detected in all somatic types in patients with pulmonary
      tuberculosis. Most substantial carbohydrate metabolic changes (curves of the
      rigid pattern) are associated with the asthenic constitution. Immunological
      changes are unassociated with the type of constitution.

PMID- 9265179
TI  - [Diagnostic difficulties in exudative pleuritis and pericarditis of specific
      etiology].

PMID- 9265180
TI  - [A case of bronchiolo-alveolar carcinoma].

PMID- 9265181
TI  - [Tuberculosis morbidity among adolescents in Kazan'].

PMID- 9265182
TI  - [Primary tuberculosis of the palatine tonsil].

PMID- 9265183
TI  - [Computer-assisted diagnosis of respiratory failure].

PMID- 9265184
TI  - [The joint meeting of the Task-Force Training Guideline Commission on
      Phthisiology, All Russian Center for Continuous Medical and Pharmaceutical
      Education and the Phthisiology Division,Academic Council, Ministry of Health of
      the Russian Federation].

PMID- 9265185
TI  - [The resolution adopted by the participants of the Symposium "Place of
      biochemistry in the forwarding the current concept of tuberculosis pathogenesis"
      held at the Central Research Institute of Tuberculosis, Russian Academy of
      Medical Science, Moscow, on April 25, 1996].

PMID- 9265186
TI  - [Tuberculosis epidemiological situation in the Sverdlovsk Region in 1991-1995 and
      guidelines for the service's action in the years ahead].

PMID- 9265187
TI  - [Psychological features of new male and female cases of pulmonary tuberculosis
      and their social adaptation].
AB  - Psychological examinations of new cases of pulmonary tuberculosis used a
      symptomatology questionnaire, methods for psychological diagnosis of the types of
      their attitudes to the disease, a glossary and typology of adaptive behavior.
      Neurotic disorders were revealed in 83.3% of the new cases, but they were
      encountered by 16.4% more frequently in females than in males. The males and
      females showed anosognotic and sensitive responses to the disease, respectively.
      After treatment the females more frequently developed a regressive type of
      adaptive behavior while the males displayed a dysadaptive one. The revealed
      features make it possible to make the patients' rehabilitation on an individual
      basis.

PMID- 9265188
TI  - Interactions between frequency-dependent and vertical transmission in host
      parasite systems.
AB  - We investigate host-pathogen dynamics and conditions for coexistence in two
      models incorporating frequency-dependent horizontal transmission in conjunction
      with vertical transmission. The first model combines frequency-dependent and
      uniparental vertical transmission, while the second addresses parasites
      transmitted vertically via both parents. For the first model, we ask how the
      addition of vertical transmission changes the coexistence criteria for parasites
      transmitted by a frequency-dependent horizontal route, and show that vertical
      transmission significantly broadens the conditions for parasite invasion. Host
      parasite coexistence is further affected by the form of density-dependent host
      regulation. Numerical analyses demonstrate that within a host population, a
      parasite strain with horizontal frequency-dependent transmission can be driven to
      extinction by a parasite strain that is additionally transmitted vertically for a
      wide range of parameters. Although models of asexual host populations predict
      that vertical transmission alone cannot maintain a parasite over time, analysis
      of our second model shows that vertical transmission via both male and female
      parents can maintain a parasite at a stable equilibrium. These results correspond
      with the frequent co-occurrence of vertical with sexual transmission in nature
      and suggest that these transmission modes can lead to host-pathogen coexistence
      for a wide range of systems involving hosts with high reproductive rates.

PMID- 9265189
TI  - Fluctuating asymmetry and psychometric intelligence.
AB  - Little is known about the genetic nature of human psychometric intelligence (IQ),
      but it is widely assumed that IQ's heritability is at loci for intelligence per
      se. We present evidence consistent with a hypothesis that interindividual IQ
      differences are partly due to heritable vulnerabilities to environmental sources
      of developmental stress, an indirect genetic mechanism for the heritability of
      IQ. Using fluctuating asymmetry (FA) of the body (the asymmetry resulting from
      errors in the development of normally symmetrical bilateral traits under
      stressful conditions), we estimated the relative developmental instability of 112
      undergraduates and administered to them Cattell's culture fair intelligence test
      (CFIT). A subsequent replication on 128 students was performed. In both samples,
      FA correlated negatively and significantly with CFIT scores. We propose two non
      mutually exclusive physiological explanations for this correlation. First,
      external body FA may correlate negatively with the developmental integrity of the
      brain. Second, individual energy budget allocations and/or low metabolic
      efficiency in high-FA individuals may lower IQ scores. We review the data on IQ
      in light of our findings and conclude that improving developmental quality may
      increase average IQ in future generations.

PMID- 9265190
TI  - Models of selective mating and the initiation of the Fisherian process.
AB  - The effects of various rules of selective mating on the initial stages of
      Fisherian sexual selection are investigated. A comparison of three models of
      selective mating, fixed relative preference, best of N males and absolute
      preference is provided, with a special emphasis on their mathematical properties.
      Using a two-locus haploid model of sexual selection in a polygamous population, I
      show that the absolute preference rule of selective mating may lower the
      threshold frequency of the preference trait, required for the initiation of the
      Fisherian process, as low as zero. This was not observed in the previous analyses
      with fixed relative preference or best of N male rules. It is then argued that
      absolute preference may cause the initiations of the Fisherian process more
      easily without introducing additional assumptions such as pleiotropy or random
      genetic drift. Some problems associated with the mating rule are also discussed.

PMID- 9265191
TI  - Computer-enhanced emotion in facial expressions.
AB  - Benson & Perrett's (1991 b) computer-based caricature procedure was used to alter
      the positions of anatomical landmarks in photographs of emotional facial
      expressions with respect to their locations in a reference norm face (e.g. a
      neutral expression). Exaggerating the differences between an expression and its
      norm produces caricatured images, whereas reducing the differences produces 'anti
      caricatures'. Experiment 1 showed that caricatured (+50% different from neutral)
      expressions were recognized significantly faster than the veridical (0%,
      undistorted) expressions. This held for all six basic emotions from the Ekman &
      Friesen (1976) series, and the effect generalized across different posers. For
      experiment 2, caricatured (+50%) and anti-caricatured (-50%) images were prepared
      using two types of reference norm; a neutral-expression norm, which would be
      optimal if facial expression recognition involves monitoring changes in the
      positioning of underlying facial muscles, and a perceptually-based norm involving
      an average of the expressions of six basic emotions (excluding neutral) in the
      Ekman & Friesen (1976) series. The results showed that the caricatured images
      were identified significantly faster, and the anti-caricatured images
      significantly slower, than the veridical expressions. Furthermore, the neutral
      expression and average-expression norm caricatures produced the same pattern of
      results.

PMID- 9265192
TI  - 5-Lipoxygenase and cyclooxygenase inhibitory active constituents from Qianghuo
      (Notopterygium incisum).
AB  - The n-hexane extract of Qianghuo (underground parts of Notopterygium incisum Ting
      x H.T. Chang, Umbelliferae) showed inhibitory activity in vitro in 5-lipoxygenase
      (5-LO) and cyclooxygenase (COS) assays. Two major constituents, phenethyl
      ferulate and falcarindiol, and one minor compound (-)-bornyl ferulate, were
      identified as the main active principles. The correlation between the content of
      active constituents and the inhibitory activity of the extracts was examined with
      seven commercial drug samples from different sources. It was obvious that the
      content of phenethyl ferulate was mainly responsible for the COX inhibitory
      activity of the extracts and falcarindiol for 5-LO inhibitory activity. Since the
      main active constituents phenethyl ferulate and falcarindiol can easily be
      quantified by HPLC, this is a suitable method for standardization and
      characterization of the drug.

PMID- 9265193
TI  - Complement-modulating properties of a kaempferol 7-O-rhamnosylsophoroside from
      the leaves of Morinda morindoides.
AB  - A kaempferol 7-O-rhamnosylsophoroside isolated from the leaves of Morinda
      morindoides showed dose-dependent complement-modulating properties towards both
      the classical (inhibiting effect) and alternative (activating effect) pathways of
      the complement system. Its structure was elucidated by chemical and spectroscopic
      methods as kaempferol 7-O-[alpha-L-rhamnopyranosyl-(1-->6)]-[beta-D
      glucopyranosyl-(1-->2)]-be ta-D-glucopyranoside, a new natural product which was
      named morindaoside.

PMID- 9265194
TI  - Triterpenoids and steroids of Myrsine africana leaves.

PMID- 9265195
TI  - [Sense of coherence and psychosomatic treatment outcome. An empirical study of
      salutogenesis].
AB  - According to Aaron Antonovsky's model of salutogenesis health protective
      resources by him conceptualised as "sense of coherence" (SOC) determine
      decisively the ability to recuperate. We investigate the relationship between
      treatment outcome and the sense of coherence measured by the SOC questionnaire at
      the beginning (n = 81), during the inpatient treatment phase and 6 month later (n
      = 70). For testing the psychometric qualities we obtained additional data from
      the outpatient department (n = 461). SOC-Score increased significantly during
      inpatient treatment. Outcome of treatment could not be predicted by the initial
      SOC, but we found a highly significant relation between an increase in the SOC
      value and a decrease in complaints (SCL-90-R, r = .81). In our opinion, the
      application of the SOC in psychosomatic patients is restricted, because there is
      a high overlap with psychic complaints (i.e. anxiety, depression).

PMID- 9265196
TI  - [Testing a screening strategy for identifying psychosomatic patients in
      gynecologic practice].
AB  - In a pilot-study 103 gynecological outpatients answered a gynecological
      questionnaire (FGB) including items of the (non-gynecological) complaints
      questionnaire (GBB) and a mood questionnaire (BSF). Cluster analyses of the FGB-
      and BSF-scores identify four groups. One group, consisting of 26 outpatients (=
      25%), has as high GBB- and BSF-scores as a group of 256 psychosomatic in-patients
      answering these questionnaires at the beginning of their psychosomatic therapy.
      These 26 outpatients are labeled as high risk patients. Further results show high
      correlations between all FGB- and GBB-scores among the gynecological outpatients.
      A significant connection between the four group classification and ten
      biopsychosocial variables is found only for the variable professional state. The
      results are seen as a first confirmation of the tested screening-strategy.
      Moreover they give evidence that further investigations should pay more attention
      to the connection between job strain and gynecological complaints or disorders.

PMID- 9265197
TI  - [Do psychological factors modify survival of cancer patients? I: Review of the
      literature].
AB  - The present paper addresses the question whether psychological factors influence
      the course of the disease in cancer patients. Studies investigating this issue
      are reviewed from a methodological point of view. The main objective is to design
      guidelines for future research. The review begins with Greer's and his co
      workers' study on breast cancer patients. They demonstrated that ways of coping
      called fighting spirit and denial are predictive of longer survival. However,
      axillary lymph node status and oestrogen receptor status could not be controlled,
      because these measures had not been assessed on a routine basis at the time of
      diagnosis. The Greer study has been stimulating a series of replications.
      Moreover, investigations into patients with various other cancer sites including
      melanoma and lung cancer have been performed. In general, results were
      inconsistent. Studies with positive findings are contrasted by those with
      negative results. Within positive findings, results were partially contradictory.
      Moreover, most of the investigations suffered from serious methodological
      limitations rendering interpretation difficult. The following methodological
      conclusions can be drawn: Testing of a priori hypotheses instead of multiple
      retrospective tests; prospective design to prevent that psychological predictors
      turn out to be indicators of the somatic state of the patient; multi-method and
      longitudinal assessment of coping and adaptation; homogeneous sample; taking into
      account all known biological prognostic factors; multivariate statistical
      analysis.

PMID- 9265198
TI  - [Therapeutic effects of the Feldenkrais method "awareness through movement" in
      patients with eating disorders].
AB  - Based on the movement-pedagogical concept of Feldenkrais and the findings-of
      disturbed body perception by eating disordered patients this research aimed at
      studying the therapeutical effects of the Feldenkrais Method "Awareness through
      Movement" with eating disorder patients, 15 eating disordered patients treated at
      the Roseneck hospital for behavioural medicine rated-by means of a questionnaire
      consisting of scales of the Body Cathexis Scale (BCS), the Body Parts
      Satisfaction Scale (BPSS), the questionnaire for body perception (Fragebogen zum
      Korpererleben; FKE), the Emotion inventory (Emotionalitatsinventar; EMI-B), the
      Anorexia-Nervosa-Inventory for Self-rating (ANIS) and the Eating Disorder
      Inventory-2 (EDI)-various aspects of their eating disorder before and after
      participating in a nine hour course of the Feldenkrais Method. The data of these
      patients were compared to those of the members of a control group, also
      consisting of 15 eating disordered patients who did not participate in a
      Feldenkrais course. The participants of the Feldenkrais-course showed increasing
      contentment with regard to problematic zones of their body and their own health
      as well as concerning acceptance and familiarity with their own body. Other
      results were a more spontaneous, open and self-confident behaviour, the decrease
      of feelings of helplessness and decrease of the wish to return to the security of
      the early childhood, which indicates the development of felt sense of self, self
      confidence and a general process of maturation of the whole personality. The
      outcome points to the therapeutical effectiveness of the Feldenkrais Method with
      eating-disorder patients within a multimodal treatment program.

PMID- 9265199
TI  - [Self-reflection, interpersonal behavior and psychoanalytic ethics].
AB  - In the middle ages, ethical practice included a metaphysical theory of value. In
      comparison with that, self-reflection and interpersonality should be described as
      principles of more individual ethics and proceeding from philosophy to
      psychoanalysis in modern times. Drawing a borderline between human philosophy and
      metaphysies, Kant defined his so-called categorial imperative as a basic
      phenomenon of human reciprocity. Ethical relationship to another person, however,
      requires realization of one's own self, i.e. self-reflection. Hegel's subsequent
      association of intersubjectivity and selfreflection supplied the basis for
      Sarte's constitution of consciousness: Existence as existing for the good of the
      fellow-being. Self-reflection, basing on the sight of one's own self by the other
      person, leads to Sartre's concept of existential psychoanalysis and to his
      understanding of ethics. His concept illustrates the decline of significance of
      philosophy for the analysis of human relationship. Habermas describes self
      reflection and interpersonality as fundamental principles of the psychoanalytic
      therapy and its ethical demands. With the historical concept of the super-ego,
      Freud established therapeutical one-sidedness and abstinence from ethics;
      however, as therapeutical interrelationship continued to intensity, ethics of
      depth psychology also began to develop. This ethical demand was not expressly
      formulated within the context of psychoanalysis, with the exception of jung and
      his epigones. Nevertheless, psychoanalytic interaction implies the development of
      self-reflection, which definitely represents a step forward in the sense of
      "ethical enlightenment" represented by Kant.

PMID- 9265200
TI  - [Evaluate your reimbursement distribution guidelines for legal conformity!].

PMID- 9265202
TI  - [Telediagnosis: from CT availability to diagnostic center?].

PMID- 9265201
TI  - [Where does the path of reimbursement politics lead?].

PMID- 9265203
TI  - [Radiology quality circle. An initiative by radiologists--quality movement within
      radiology].

PMID- 9265204
TI  - [Federal recommendation and its application to the area of hospital insurance].

PMID- 9265205
TI  - [Importance of magnetic resonance tomography in radiology. No MRI specialty for
      other areas! Combined position of DRG and BVDRN].

PMID- 9265206
TI  - [Euro-PET in Freiburg: new cooperation between individual clinic and established
      physicians].

PMID- 9265207
TI  - [Electronic data processing in general practice: BVDRN recommends the
      WinRadiolog. Special price for members].

PMID- 9265208
TI  - [Practice closure also possible as of 1999. Limitations and value protection].

PMID- 9265209
TI  - [Cost pressure in health care. Teleradiology].

PMID- 9265211
TI  - [Requirements for a teleradiology system. Experiences with the MEDICUS-2 field
      test].
AB  - During the Medicus field test we gained experience using the teleradiology system
      for almost daily teleconferences between a radiology department and clinics for
      internal medicine, urology, and gynecology. The existing system has a high degree
      of functionality. The full 12-bit data format is available using the DICOM
      protocol. A data security concept is implemented, ensuring data integrity,
      privacy and authentication of communication partners. This concept covers the
      areas of organization, technique, user training, and software implementation. A
      future system should be a general purpose radiology workstation covering viewing
      functionality, image manipulation, and digital archive access. Dedicated
      teleradiology features have to be a part. Specialized evaluation software, e.g.
      for dynamic MRI, should be integratable in a modular way. For data exchange with
      other systems and for the synchronization of teleconference sessions, the
      protocols should be independent of the network standard used (ISDN, Ethernet,
      ATM) and based on the DICOM protocol. Extensions of the existing standard are
      therefore necessary. Besides future technical developments, reimbursement for
      teleradiology must be accomplished.

PMID- 9265210
TI  - [Goals, requirements and prerequisites of teleradiology. An assessment of current
      status].
AB  - Specific radiological requirements have to be considered for the realization of
      telemedicine. In this article the goals and requirements for an extensive
      introduction of teleradiology will be defined from the radiological user's point
      of view. Necessary medical, legal and professional prerequisites for
      teleradiology are presented. Essential requirements, such as data security,
      maintenance of personal rights and standardization, must be realized. Application
      specific requirements, e.g. quality and extent of teleradiological functions, as
      well as technological alternatives, are discussed. Each project must be carefully
      planned in relation to one's own needs, extent of functions and system selection.
      Topics, such as acknowledgement of electronic documentation, reimbursement of
      teleradiology and liability, must be clarified. Legal advice and the observance
      of quality guidelines are recommended.

PMID- 9265213
TI  - [Advantages and cost-benefit analysis of various teleradiology scenarios].
AB  - With the increasing number of users and technical improvements, there are several
      application scenarios of teleradiology. To perform a cost-benefit analysis, an
      approach is presented, which focuses on both monetary and qualitative aspects.
      Process-related, qualitative and quantitative evaluations are described. The
      prestudy compares the radiological workflow before and after the introduction of
      a teleradiology system. A scoring model is part of the qualitative evaluation.
      The quantitative study focuses on costs and savings. Amortisation and a net
      present value of savings versus costs can be derived using dynamic investment
      methods. Savings can be achieved after a short time under ideal conditions, but
      there is no guarantee for a reimbursement for all systems.

PMID- 9265212
TI  - [Possible applications of the KAMEDIN teleradiology system with special reference
      to an economic analysis].
AB  - INTRODUCTION: Different concepts and applications of teleradiology systems have
      been realised. However, their cost-effectiveness is still questionable.
      Therefore, a cost-benefit analysis of three different scenarios of the new
      teleradiology system Kamedin (Kooperatives Arbeiten und rechnergestutzte
      Medizinische Diagnostik auf innovativen Netzen der Deutschen Telekom) was
      performed. METHODS: CT examinations were transmitted from an Advantage Windows
      (GE) workstation to a Kamedin workstation using DICOM 3 protocol. Afterwards a
      teleconference was established with a Kamedin workstation in the intensive care
      unit within the hospital via FDDI/Ethernet, with an external workstation in a
      radiology department 6 km away via ISDN and with a Kamedin PC located with
      radiologist on duty 22 km away via ISDN. On average, 36 CT slices per patient
      were transferred. A break-even analysis was performed with respect to costs of
      hardware, software, support, use of ISDN and staff, as well as benefits like the
      decrease in transportation or film documentation costs. RESULTS: Owing to the
      different reductions in transportation costs, two applications (intensive care
      unit and external PC) showed a break-even of 1817 and 528 teleconferences/year,
      respectively. Further optimisation of cost-effectiveness is possible on condition
      that existing hardware can be used and an automatic data transfer without staff
      control is available. When all optimisation factors were combined, the break-even
      decreased to a minimum of 167 and 77 teleconferences/ year, respectively.
      CONCLUSION: Teleconferences with high image quality can be set up between
      workstations and PCs using the Kamedin system. Depending on the possible decrease
      in transportation costs, teleconferencing is cost-effective under certain
      conditions. Teleradiology has additional advantages, such as the acceleration and
      optimisation of patient management.

PMID- 9265214
TI  - [Telemedicine. Possibilities and perspectives].
AB  - The discussion about the implementation of telemedicine and teleresourcing and
      its consequences has been under way for some time now. The rate at which
      telemedical applications are being developed, leaves little time for
      consideration of the economic, scientific and social aspects. There is a need for
      integration of all the existing fragments into one coherent telemedical concept.
      Different aspects of telemedical concepts are discussed.

PMID- 9265215
TI  - [Teleteaching with CONRAD. From collected cases to interactive learning system].
AB  - Radiological teaching files on the Internet suffer from certain restrictions such
      as limited user interactivity. The Internet teaching project CONRAD (computer
      online network for radiological didactics) circumvents these restrictions by
      using a new database structure that also reflects the development of a diagnosis
      over time. The cases are presented in the internet with different HTML-based
      teaching programs. To support interactivity, CONRAD offers the building of online
      learning groups over the internet.

PMID- 9265216
TI  - [Strategy for securing medical documents by electronic signature and encryption].
AB  - The paper presents a survey of security strategies for the protection of medical
      documents which are generated, stored, and exchanged electronically. It is not
      meant to provide a precise technical background but to give a guideline for
      interested medical professionals. A systematic approach for the definition of
      appropriate security requirements is outlined, and generally accepted security
      functions (services) are described. The major part of the paper is dedicated to a
      technical introduction to state-of-the-art security mechanisms based on
      cryptographic methods. Finally, actual implementation problems and perspectives
      are discussed from a German/European viewpoint.

PMID- 9265217
TI  - [Legal aspects of teleradiology].
AB  - It is hoped that the implementation of teleradiology will improve the quality and
      economic effectiveness of health care in the future. The German federal
      government has submitted a bill for a legal statute, thereby creating the
      necessary framework to guarantee the essential "document security". The
      responsibility of those involved with orderly data transmission as well as the
      limited responsibility for physicians' findings are both governed by general
      liability. General principles apply also with regard to professional discretion.
      Authorized utilization of external networks depends upon the quality of data
      security. Networks with unlimited-public access may not be used without explicit
      consent from those concerned.

PMID- 9265218
TI  - [Value of ultrasound imaging of the Achilles tendon in traumatology].
AB  - METHOD: In an experimental study on ten isolated human cadaver tendons, the
      ultrasound anatomy and the reproducibility of artefacts was determined using 10-
      and 13-MHz probes. With these in vitro data, the form and diameter of a non
      injured tendon were documented in a series of 30 patients between 3 and 60 years
      old. In a second series of 32 patients with acute, traumatic ruptures of the
      Achilles tendon and 40 patients with chronic disorders, we distinguished the
      pathological anatomy. RESULTS: Injuries to a tendon with chronic disorders,
      reruptures and complications in the postoperative period after tendon repair can
      be made more difficult by calcification, scars, oedema, haematoma and suture
      materials. It is necessary to check the changing ultrasound patterns owing to an
      haematoma or oedema with tendon carpulence, the missing linear signals in a fresh
      rupture and the different signals after operative or nonoperative treatment.
      CONCLUSION: Using high-frequency probes with 10 or more MHz, it is possible to
      examine even the insertion area of the tendon or the pathology of a subachilleal
      bursa by tilting the probe. The dynamic examination and the comparison with the
      contralateral side in two planes should be included in a standardized examination
      procedure and are of great importance in some cases of fresh tendon ruptures.
      Knowledge of the physical principles and the possibility of misleading artefacts
      is crucial.

PMID- 9265219
TI  - [An unusual symptom complex of the upper cervical spine. Tendinitis calcarea of
      the longus colli muscle].

PMID- 9265220
TI  - [Acute abdomen with palpable resistance in the pelvis and painful kidney region.
      Acute retroperitoneal hemorrhage from angiomyolipoma kidney in tuberous sclerosis
      (Bourneville-Pringle disease)].

PMID- 9265221
TI  - [Commercial teleradiology systems in Germany].
AB  - Teleradiologysystems can differ considerably in their features. The most
      important differences lie in the mode of image data acquisition, data transfer,
      data safety aspects and the possibilities of interaction between separate
      teleradiology units. A selection of commercially available teleradiologysystems
      is presented and compared.

PMID- 9265222
TI  - [The resistance of Biomphalaria glabrata to Schistosoma mansoni infection:
      variations in the prepatent period and in compatibility].
AB  - Biomphalaria glabrata from Belo Horizonte, Minas Gerais, Brazil, reared in
      laboratory, has a level of infection of 90% when exposed to 20 miracidia of the
      autochibonous LE strain. The prepatent period was of 5 to 7 weeks whereas 5 to
      10% of exposed snails do not shed cercariae. The eggs of negative snails were
      collected and the progeny was again submitted to individual infection with 20
      miracidia. The mean of infection from F14 to F20 was of 43.6%. Histological
      sections from F12, F14 and F15 snails showed tissue reactions in those specimens
      shedding less than 10 cercariae. A prepatent period of 17 to 32 weeks was
      observed in 35 (17.9%) of 195 infected snails. The index of cercariae of control
      was extremely compatible and for F12, F13 and F15 snails varied from very
      compatible class V to compatible class III, showing less compatibility in
      selected snails.

PMID- 9265223
TI  - [A description of Aedes aegypti colonization in the region of Sao Jose do Rio
      Preto, Sao Paulo].
AB  - The aim of this study is to describe the colonization by the Aedes aegypti in the
      region. A survey carried out in 1985 detected the species in Sao Jose do Rio
      Preto. The mosquito has spread and reached the 30 countries of the region till
      1988. In the district and rural areas, the first vector focus was found out in
      1987 in one of the 29 districts and rural areas, having spread to the others till
      1991. The foci have been mainly identified through larval researches in locations
      with a great concentration of containers, and the greatest occurrence of larvae
      of Aedes aegypti has been in tires, the most frequent means of spread. The foci
      have been mainly identified between November and April, periods of greater
      incidence of rains. The delimits of foci showed that the containers which were
      mostly infested by the mosquito in homes have been tires and vases of plants. The
      most important consequence of the presence of Aedes aegypti has been the
      occurrence of dengue epidemics.

PMID- 9265224
TI  - [Dermatophytoses in the urban environment and the coexistence of man with dogs
      and cats].
AB  - There have been submitted to clinical exam in laboratory of dermatophytosis and
      inquired about possible contact with domestic animals (dogs and cats) 158
      patients living in the urban area of Fortaleza, that showed lesions suspected of
      dermatophytosis. This search associated to the obtained data in questionnaires
      permitted us to identify the frequency of domicile outbreaks. Within the 83
      people with dermatosis isolated of human infections, prevailed the anthropophilic
      species over the zoophilic ones, and that it was observed a confluence of human
      and animal diagnosis in 100% of the human dermatophytosis zoophilic cases, where
      the same species were identified in men and contacting animals: M. canis and T.
      mentagrophytes. As the patients carrying anthropophilic dermatophytosis varied as
      to the contact with animals, not having been these fungus isolated from none of
      the contacting animals. Before the low frequency of zoophilic dermatophytosis, it
      was considered that the intimacy of men with domestic dogs and cats represented
      was little as a conditional factor of occurrence of dermatophytosis in the urban
      environment.

PMID- 9265225
TI  - [The epidemiology of accidental bites by venomous snakes in the state of Ceara,
      Brazil].
AB  - From 1992 to 1995, 688 accidents by venomous snakes (mean of 192 cases/year) have
      been notified to the Health Ministry of the State of Ceara, with an incidence
      between 0.9 and 5.8/100.000 inhabitants. Among 473 cases, 88.3% were of the
      genus. Bothrops, 10.7% Crotalus, 0.8% Micrurus and 0.2% Lachesis. The highest
      incidence occurred from April to September. Male (75.6%) predominated with ages
      from 10 to 49 years old (72.3%). The more frequently bitten anatomical region
      were the lower limbs (81.9%) and upper limbs (14.7%). The attendance at health
      unit which notified the accident took place within 6 hours in 66.9% of the cases.
      Lethality was 0.7%. The afflicted people were mainly peasants (62.7%), and most
      of the accidents took place in their own work place. The authors emphasize that
      the snake bites in the state of Ceara may be considered work accidents, concern
      mainly peasants and constitute a cause of death.

PMID- 9265226
TI  - [Chromoblastomycosis in Rio Grande do Sul: a report of 12 cases].
AB  - Twelve cases of chromoblastomycosis diagnosed in Rio Grande do sul during 1988
      1995 are reported. The clinical aspects are analyzed and compared with the
      literature. Fonsecaea pedrosoi was the only microorganism isolated.

PMID- 9265227
TI  - [Schistosomiasis and viral hepatitides: a review].
AB  - The papers published on the association of schistosomiasis with viral hepatitis
      (B, C and D) are reviewed. The shortcomings of each work are pointed out and
      suggestions are forwarded to try and direct the investigations on this probable
      interaction.

PMID- 9265228
TI  - [A cutaneous ulcer induced by fungi of the genus Fusarium].
AB  - A case of cutaneous hyalohyphomycosis, due to Fusarium oxysporum, in a 40 years
      old man is presented. The patient came from Paraguay where he worked in a
      tropical rural area. His disease had begun 2 months before his admission as a
      skin ulcer located in the left leg. Clinical characteristics, diagnosis methods,
      differential diagnosis with other ulcers of the legs in tropical areas as well as
      therapeutic measures are discussed in this presentation.

PMID- 9265229
TI  - [Nasofacial zygomycosis in the state of Para: the registration of 2 cases].
AB  - Two new cases of nasofacial zygomycosis from the state of Para, Brazil, are
      reported. Both cases were treated with ketoconazole and the response to the drug
      was considered to be good; the patients improved rapidly and the nasal
      obstruction was the first manifestation to disappear. As five cases have been
      described in recent years from the state of Para, this form of zygomycosis can no
      longer be considered as a rare disease in northern Brazil.

PMID- 9265230
TI  - [The finding of Panstrongylus megistus in an artificial ecotope: taking up
      residence or merely visiting?].
AB  - As a first measure of Chagas' disease control in Brazil with chemical elimination
      of the most important vector of the disease, Triatoma infestans was removed.
      Attention is now being paid to Triatoma sordida and Panstrongylus megistus. That
      species can eventually be found inside houses, as happened with the specimens we
      examined from Bernardino de Campos and Sete Barras, all of them infected by
      Trypanosoma cruzi. These data suggest that a better knowledge about the behavior
      that species is needed to introduce changes in the control measures.

PMID- 9265231
TI  - [Is glomerulopathy due to schistosomiasis mansoni disappearing?].
AB  - Hepatosplenic form of S. mansoni infection may be accompanied by a glomerulopathy
      in 12-15% of cases, manifested in the majority by a nephrotic. This type of renal
      involvement is becoming a rare occurrence in our University Hospital (Hospital
      Universitario Prof. Edgard Santos) a typical general hospital in an endemic state
      for this parasitic disease. To investigate this fact, autopsied cases with
      patients with hepatosplenic form of schistosomiasis mansoni during two decades in
      our Hospital-1960-70, (before a therapeutic intervention in endemic areas with
      oxamniquine) and 1980-1990 (after the intervention) were compared in reference to
      number of cases and the finding of glomerulonephritis by histological
      examination. Even though there was a striking decrease in number of patients with
      advanced forms of this disease (140 as compared to 31 autopsies in these two
      decades), the prevalence of glomerulonephritis diagnosed was 11.4 (16 cases) in
      the first and 12.9 (4 cases) in the second. As there was no change in pattern of
      attendance in this Hospital, the drastic decrease in number of severe forms of
      this parasitic infection following massive therapy of the endemic population with
      oxamniquine is the most likely explanation not only for the decrease in number of
      hepatosplenic cases but, also, and as a consequence, the scarcity of cases of the
      schistosomal glomerulopathy observed.

PMID- 9265232
TI  - [125 years of the Serbian Medical Society. Traditions which arose in history,
      values which endure].

PMID- 9265233
TI  - [Survival analysis in patients with cutaneous malignant melanoma].
AB  - INTRODUCTION: Cutaneous malignant melanoma (MM) takes only 3% of all malignant
      tumours of the skin, but for reason of its increased frequency and pronounced
      tendency to rapid growth and metastases, it causes 60% of total lethal outcomes
      due to malignant tumours of the skin [1]. Primary MM is a diagnostic problem
      because of the great variety of its clinical features. Asymmetric configuration,
      irregular border, speckled color(r)diameter of more than 6 mm, and elevation of
      the surface, suggest suspicion of malignant alteration, but even then
      misdiagnosis is possible. For the final diagnosis of MM histopathological
      confirmation is necessary. The method to use is the extensive excisional biopsy
      of the lesion and its borders [2]. Histopathological diagnosis is based on
      microscopic findings which include: histogenetic type of MM, tumour thickness
      according to Breslow, level of invasion according to Clark, presence of
      ulceration, grade of lymphocyte infiltration, mitote rate, type of cells,
      presence of melanin in cells [2, 3]. PATIENTS AND METHODS: A five-year survival
      of patients with cutaneous malignant melanoma (MM) was studied according to sex,
      age and distinct features of the tumour: site, type of initial therapy, stage of
      the disease, time from the first signs of the disease to diagnosis of MM,
      histological findings (histogenetic type, Breslow's tumour thickness, Clark's
      level of invasion, presence of ulceration, degree of lymphocyte infiltration,
      number of mitoses, type of cells, intensity of pigmentation) and presence of
      metastases. The retrospective study included 336 patients with cutaneous MM.
      There were 185 female (55.1%) and 151 male patients (44.9%), aged 14-83 years,
      mean age 48.8 years, who were treated at the institute of Oncology and Radiology
      in Belgrade from 1978 to 1990. The mean follow-up was 60 months (1-144 months).
      Melanoma in situ had 16 (4.1%) patients. Stage I had 45 patients (14.1%), stage
      II 163 (48.5%), stage III 83 (24.7%) and stage IV 29 (8.6%) patients. Acral
      location on hands and feet had 40 (11.9%) patients, on head and neck 36 (10.7%),
      on the trunk 146 (43.5%) and on the extremities (except hands and feet) 114
      (33.9%) patients. Nodular melanoma (NM) was the most frequent histogenetic type
      revealed in 150 (44.6%) patients, superficial spreading melanoma (SSM) in 105
      (31.1%) patients, acral melanoma (AM) in 39 (11.5%) and lentigo malignant
      melanoma (LMM) in 32 (9.4%) patients (Table 1). Five-year survival rate was
      calculated according to Kaplan-Meier's method and significance of the difference
      between some categories was tested by Long-Rank's test; the significance less
      than 0.05 was accepted. RESULTS: Statistically highly significant differences in
      a five-year survival (p < 0.01) were related to sex p = 0.0005, age p = 0.0017,
      tumour site p = 0.0025, initial therapy p = 0.0036, stage of MM p = 0.0000,
      histological features of the tumour p = 0.0000 and presence of metastases p =
      0.0000. A better five-year survival prognosis was found in female patients
      (64.5%) compared to male patients 44.5%, aged 27-46 years (87.3%) compared to
      patients younger than 26 years (43.5%); patients with melanoma on the extremities
      (except hands and feet) had a better five-year survival (66.7%) compared to
      patients younger than 26 years (43.5%); patients with melanoma on the extremities
      (except hands and feet) had a better five-year survival (65.7%) compared to
      patients with melanoma on the trunk or acral melanoma (47.3%). Higher survival
      was recorded in the group of patients with the tumour 1.5-3 mm thick, in whom the
      tumours was excised and regional nodes dissected as the primary therapy (66.9%)
      compared to those who underwent excision of the tumor only (48.8%). A five-year
      survival of patients with MM in situ was 100% for those in stage I; 85% in stage
      II; 42% in stage III, 16% and 0% in stage IV. The patients in whom the diagnosis
      of MM was established within 10 months after the first signs of the disease had
      significa

PMID- 9265234
TI  - [Functional damage of the larynx].
AB  - INTRODUCTION: The basic mechanism of the development of functional voice
      disorders is an excessive collision pressure between the vocal folds during
      phonation, which occurs between the membranous folds, and/or the vocal processes.
      Functional-traumatic lesions of the vocal folds appear mainly at the junction
      between the anterior and the middle thirds of the vocal folds, slightly below the
      free edge. This is the "predilection site" of the vocal folds, which is the most
      active part of the vocal folds during phonation, and is therefore mostly exposed
      to functional-traumatic changes. This study is aimed at establishing the most
      frequent benign lesions of the vocal folds, which appear at the predilection
      sites of the vocal folds, and discussing their functional-traumatic aetiology.
      MATERIAL AND METHODS: During the past 10 years 1550 patients underwent various
      microsurgical procedures for benign lesions of the vocal folds. They were studied
      for the precise localization of the lesions by the use of indirect
      videostroboscopy or microstroboscopy, and direct microlaryngoscopy related to the
      technique which has been used in each particular patient. In this way an overall
      number of lesions was established, which were located at the predilection sites
      of the vocal folds, indicating their functional-traumatic aetiology. RESULTS: It
      has been established that 1068 lesions (68.6%) were located at the predilection
      site of the vocal folds (Table 1). Namely, these were nodular lesions, polyps,
      cysts, and haematoma. Contact hyperplasia appeared at the posterior third of the
      vocal folds due to a special mechanism of its development. DISCUSSION: Functional
      traumatic lesions are mucous stranding, nodular lesions, polyps, cysts, contact
      hyperplasia and haematoma. All these lesions are either of functional origin or
      functional voice disorders which contribute, to some degree, to their
      development.

PMID- 9265235
TI  - [Aneurysms of the carotid arteries].
AB  - The aim of the paper is the presentation of the treatment of aneurysms of the
      extracranial carotid artery and review of literature. Aneurysms of extracranial
      carotid arteries (common carotid artery, external carotid artery and cervical
      part of the internal carotid artery) are very rate [1, 2]. In 1979 McCollum from
      the Baylor University (Houston, Texas) reported 37 cases over a 21-year period
      [3]. Moreau from France reported 38 cases over a 24-year period [4]. Mayo clinic
      experience includes 25 cases in the 40-year period [5]. According to Schechter
      835 extracranial carotid artery aneurysms were reported in literature until 1977.
      These and the other aneurysms of the extracranial carotid artery can be partially
      or completely thrombosed, can cause distal embolization, or compression of
      adjacent structures, and can be ruptured [4, 9]. Therefore, the mortality rate in
      non operated patients with carotid artery aneurysm is 70% [10]. Over the period
      from January 1, 1985 to December 31, 1996 at the Centre of Vascular Surgery
      within the Institute of Cardiovascular Diseases of the Serbian Clinical Centre in
      Belgrade, 12 patients with 13 extracranial carotid artery aneurysms were treated.
      Nine of them (75%) were males and 3 (25%) females, average age 58.22 (21-82)
      years. There were two traumatic (gunshot wounds) and one anastomotic (after
      carotid subclavian bypass with PTFE graft) pseudoaneurysms, and 10 true
      atherosclerotic aneurysm. Three (23%) aneurysms were on the common and 9 (77%) on
      the cervical part of the internal carotid artery. Two (15%) aneurysms were in the
      form of asymptomatic pulsatile neck mass, 7 (54%) with CVI or TIA, three (23%)
      with compression of the cranial nerves and one (8%) was ruptured. Twelve (92%)
      patients were treated surgically, while one asymptomatic aneurysm in a 82-year
      old female patient was not operated due to high risk. The intraoperative findings
      revealed one complete and 11 partial thromboses of the aneurysmal sac. In 3
      patients with fusiform aneurysms, thrombectomy and aneurysmorrhaphy were
      performed. One traumatic pseudoaneurysm was treated with aneurysmectomy and
      lateral suture of the artery. In 3 patients aneurysmectomy and end to end
      anastomosis were done, while in three aneurysmectomy and saphenous vein graft
      interposition. In case of ruptured aneurysm of the internal carotid artery
      aneurysmetomy and arterial ligature were carried out, while in case of
      anastomotic pseudoaneurysm after carotid subclavian bypass, aneurysmectomy and
      new carotid subclavian bypass with PTFE graft, were performed. During the study
      no intrahospital mortality was recorded. One patient died 5 years after the
      operation due to myocardial infarction. The mean follow-up period was 4 years and
      2 months (6 months to 11 years). The early and late potency rates were 100%. Two
      (17%) CVI and two transient cranial nerve paresies were noticed immediately after
      the operation. In literature male/female ration in patients with extracranial
      carotid artery aneurysms is 2:1 [2, 4, 7], but in our study it was 5:1. One (10%)
      of our patients had a bilateral carotid artery aneurysm. According to literature
      data the incidence of bilateral localization of extracranial carotid artery
      aneurysms with atherosclerotic origin is 21% [1]. Of 12 surgically treated
      aneurysms in our study, 9 were of atherosclerotic origin, two were traumatic and
      one anastomotic pseudoaneurysms. Today, most of true extracranial carotid artery
      aneurysms are of atherosclerotic origin [7, 20-25]. However, true extracranial
      carotid artery aneurysms can be developed due to: infection of the arterial wall
      (mycotic forms) [26-37]; nonspecific [23] or irradiation arteritis [38],
      fibromuscular dysplasia [4, 8, 15, 16, 39]. The most frequent types of false
      extracranial carotid artery aneurysms are traumatic pseudoaneurysms [32, 50-54]
      and anastomotic pseudoaneurysms [53, 59, 60]. There are also dissecting
      extracranial carotid artery aneurysms developed after isolated spontaneous d

PMID- 9265236
TI  - [Levels of immune complexes in fresh and frozen serum and plasma detected by
      precipitation with polyethylene glycol in patients with malignant diseases].
AB  - INTRODUCTION: Immune complexes are macromolecules consisting of immunoglobulins
      (antibodies) bound to different antigens [1]. Determination of circulating immune
      complexes in patients with malignant diseases can be of some interest for
      prognosis and follow-up of a disease [2, 3]. According to certain data the immune
      complexes concentration varies in dependence of disease stage [4] and it is not
      affected by therapy [5]. Precipitation with polyethylenglycol is a physical
      method for determination of circulating immune complexes, based on the ability of
      high molecular polymers to precipitate macromolecules from sera [6]. This
      mechanism of precipitation is not yet well understood, but it is probably based
      on steric exclusion of water molecules that affects insolubility of immune
      complex molecules [7]. Repeatedly frozen sera demonstrated rapid decrease in
      detected concentration of circulating immune complexes [8] by polyethylenglycol.
      The presence of complement affects solubility of circulating immune complexes
      [7]. While there are no data about the influence of other proteins in sera or
      plasma, the aim of this study was to find out if there are any significant
      differences between the circulating immune complexes levels, determined by
      polyethylenglycol, in sera, plasma or in only once frozen sera. MATERIAL AND
      METHODS: Eighteen samples of plasma and sera from patients with malignancy (10
      males and 8 females) were examined. Eight of them had non-Hodgkin lymphoma, 4
      were with Hodgkin lymphoma, 4 with breast carcinoma and 2 with lung carcinoma.
      All samples were taken before starting chemotherapy. The circulating immune
      complexes determination was carried out immediately after the separation of
      plasma and sera and also in sera frozen for 10 days at -35 degrees C. Circulating
      immune complexes were determined spectrophotometrically. The absorbance (A450) of
      serum or plasma in 3.75% of polyethylene glycol, polyethylenglycol (M = 6000)
      solution was used as the measure of the circulating immune complexes level [9].
      The standard for circulating immune complexes determination in g/l was aggregated
      IgG at 36 degrees C for 30 minutes from the serum of healthy volunteers. RESULTS:
      The mean value and the range of circulating immune complexes level (A450) are
      given in Table 1. The values in g/l are presented in Graph 1. The values of
      circulating immune complexes in plasma were significantly lower than those in
      fresh sera (t = 2.8125; p < 0.02). There was no significant statistic difference
      between levels in circulating immune complexes (A450) in fresh and frozen sera (t
      = 1.3261; p > 0.1). DISCUSSION: In dependence on its concentration
      polyethylenglycol shows the ability to precipitate proteins selectively [10]. The
      selectivity was tested mainly towards immunoglobulins and the complement. Results
      obtained in this study show statistically significant lower circulating immune
      complexes level in plasma than in serum or frozen serum. The main difference
      between sera and plasma is in complete absence of fibrinogen, factors V and VIII
      in sera and in presence of Ca++ ions. Besides that plasma contains an
      anticoagulant [11]. It is possible that the presence of fibrinogen and some
      coagulation factors disturb the polyethylenglycol precipitation mechanism.
      According to this, it might be, that mechanism, based on steric exclusion of
      water molecules, selectively influences polyethylenglycol precipitation of
      circulating immune complexes in plasma. It is difficult to say how much Ca++ ion
      and anticoagulant, as well as the activity of some plasma enzymes, and possible
      dissociation of circulating immune complexes influence the formation of
      precipitate. In any case, there is a significant difference between concentration
      of circulating immune complexes according to substrate. For that reason, it is
      necessary to detect circulating immune complexes by polyethylanglycol always in
      the same medium for exact clinical evaluation. (ABSTRACT TRUNCATED)

PMID- 9265237
TI  - [Posttraumatic acute renal insufficiency].
AB  - Acute renal insufficiency is a severe, but most frequent reversible illness
      followed by sudden onset, oliguria or anuria of indefinite duration, by rapid
      increase in decomposition products of protein catabolism in serum, by acidosis
      and fluid balance and electrolytes disorder. The aetiologic factors of acute
      renal insufficiency are various. A very significant aetiological factor in the
      appearance of acute renal insufficiency is a trauma caused by any kind or type of
      weapons, arms or instruments [1-5, 6, 9-13, 15]. Of a total number of injured
      persons who were treated in our institution (4,086 injured persons), 251 (6.14
      percent) were with acute renal insufficiency, and of that number with all signs
      and symptoms of acute renal insufficiency 37 (0.9 percent) were treated with
      haemodialysis. Of the number of dialysed patients 30 (80 percent) patients had
      oliguric form of acute renal insufficiency and 7 (19 percent) were with non
      oliguric form of acute renal insufficiency. The most frequent injuries were to
      abdomen and then to extremities, liver, chest and kidneys. The smallest
      percentage concerned isolated injuries in extremities. According to a pathogenic
      mortality mechanism, the highest mortality was in patients with haemorrhagic
      syndrome and in septic condition, and the minimal in patients with other
      syndromes, such as crush syndrome, etc. In 25 (68 percent) patients acute renal
      insufficiency was associated with haemorrhagic syndrome, in 7 (18.9 percent) with
      crush syndrome and in 5 (13.5 percent) with septic condition. In 36 (97 percent)
      patients haemodialysis was performed and in 1 (3 percent) subject peritoneal
      dialysis. The reason for such a small number of peritoneal dialysis are severe
      injuries to abdomen and chest, since this type of dialysis could not be performed
      for technical reasons. In 27 (73 percent) patients haemodialysis was performed as
      a type of intermittent heparinization. In 5 (14 percent) patients heparinization
      was a type of continual heparinization. Thanks to prompt haemodialysis together
      with medical therapy and surgical treatment, the mortality rate in our patients
      was lower in comparison to mortality rate in other centres (Table 3). The main
      causes of acute renal insufficiency in our patients were: Acute tubular nercosis,
      peripheral blood flow insufficiency (hypovolaemia, cardiovascular failure), and
      postrenal insufficiency (excretory obstruction, intrarenal obstruction, urinary
      organ ruptures, haemorrhagic shock) and the underlaying kidney disease. Acute
      renal insufficiency can be divided into acute renal insufficiency, primary
      parenchymal renal insufficiency and postrenal azotaemia [1-6, 9, 12, 13]. During
      the therapy of these patients it is important to evaluate the dehydration degree
      of patients by clinical and laboratory parameters. In case of hypovolaemia the
      complete compensation of fluid should consist of infusion together with
      administration of diuretics. The central venous pressure should be maintained at
      the values in a range from 6 to 8 cm H2O. In case of oliguric acute renal
      insufficiency the fluid intake should be equal to diuresis plus every other loss
      of fluids. Diet should be high-caloric with carbohydrates in the amount of 100
      mg, and that amount should be given three to four times daily (both parenterally
      and orally) together with restriction of potassium intake due to a well known
      effect of potassium on myocardium function. Dosage of drugs which are eliminated
      via kidney should be managed promptly by parenteral administration of antibiotic
      agents [7, 8, 13-16]. Haemodialysis should be started at the very beginning of
      the patients admission to the hospital and should be associated with
      anticoagulant therapy for avoiding haemorrhages. Thanks to haemodialysis
      performed in time, the mortality rate in our patients was reduced in comparison
      to health centres where haemodialysis was delayed. Thanks to such treatment of
      patients with many severe injuries in whom the mortality rate is usuall

PMID- 9265238
TI  - [The effect of hemodialysis and continuous ambulatory peritoneal dialysis on
      renal anemia].
AB  - Anaemia is an almost invariable sign of chronic renal failure [1]. Although many
      factors have been implicated as causes of this anaemia, it seems probable that
      deficiency of erythropoietin is the main cause for most patients [2]. Institution
      of chronic dialysis can improve anaemia in end-stage kidney disease, continuous
      ambulatory peritoneal dialysis being reported as more successful [3]. The aim of
      this study was to investigate the influence of haemodialysis and continuous
      ambulatory peritoneal dialysis on anaemia during the first six months of
      treatment. We examined 21 persons (14 males and 7 females, aged from 18 to 78
      years) on haemodialysis treatment and 13 persons (6 males and 7 females aged from
      22 to 64 years) on continuous ambulatory peritoneal dialysis (Table 1). Standard
      procedures were used for measuring biochemical parameters. Urea and creatinine
      levels were high, almost incompatible with life, in all tested persons before
      dialysis treatment. During the first three months of both dialysis techniques
      urea and creatinine were significantly (p < 0.01) corrected, but remained above
      the normal ranges (Table 2). Patients on continuous ambulatory peritoneal
      dialysis have shown significantly (p < 0.01) lower urea and creatinine values
      compared to patients on haemodialysis (Graph 1). These data suggest better
      preservation of renal function and better control of the internal environment
      during continuous ambulatory peritoneal dialysis [6]. All tested patients were
      severely anaemic before the beginning of dialysis. During the first six months of
      haemodialysis erythrocyte count, haematocrit and haemoglobin levels were
      unchanged (Table 3). Transfusions and hepatitis episodes only temporary improved
      anaemia. Patients on continuous ambulatory peritoneal dialysis exhibited
      significant correction of anaemia already during the first three months of
      treatment (Graph 2). Though less significantly, haemoglobin values continued to
      rise even during the next three months. The reached haemoglobin levels were lower
      than normal, but significantly higher than values in patients on haemodialysis (p
      < 0.01), suggesting better control of anaemia during continuous ambulatory
      peritoneal dialysis. Transfusion requirement was irrelevant, and hepatitis was
      not noticed, so they cannot be held responsible for the improvement of anaemia.
      Greater iron consumption, illustrated by higher transferrin saturation, also
      confirmed increased erythopoitesis in patients undergoing continuous ambulatory
      peritoneal dialysis. They also had lower blood iron level than those on
      haemodialysis (who had) numerous blood transfusions. The improvement of anaemia
      during continuous ambulatory peritoneal dialysis may be the result of reduction
      in plasma volume [7] as well as an increase in red cell mass and a better
      clearance of middle molecules in comparison to patients on haemodialysis. The
      main cause is higher erythropoietin level [8]. All tested patients had low folic
      acid level. Patients who corrected anaemia showed fall in folat level. This was
      statistically remarkable during the first three months of continuous ambulatory
      peritoneal dialysis-from 3.64 ng/ml to 2.09 ng/ml. All these data suggest that
      both dialysis modalities are effective in the control of protein waste products
      level, but continuous ambulatory peritoneal dialysis has better influence on the
      improvement of anaemia that haemodialysis. This can be attributed to better
      removal of uremic toxins, improved protein metabolism, lower parathyroid hormone
      level and higher erythropoietin value due to peritoneal macrophage production.

PMID- 9265239
TI  - [The effect of knowledge regarding the importance of oral health in pregnancy].
AB  - INTRODUCTION: Although in modern dental medicine a pregnant woman and her foetus
      are completely safe during all dental procedures, the prevention is still the
      most effective measure for the preservation of oral health in pregnancy. However,
      pregnant women often visit a stomatologist only when there are already serious
      disturbances, regardless of the fact that they are referred to a stomatologist
      even at their first visit to a gynaecologist. The aim of the study was to
      investigate (possible) changes in pregnant women's attitudes toward oral health
      during pregnancy according to our educational programme. METHODS: One hundred and
      sixty pregnant patients were randomly selected for the educational programme and
      were enrolled in the study. In direct contact (groups of 4 to 14 pregnant
      patients) they received basic information about the condition for attaining and
      maintaining their and foetal good health [1]. In order to establish the results,
      three anonymous questionnaires were conducted. Two of them made the questionnaire
      A because of identical results obtained before and after the education, and the
      third questionnaire B was different, and was conducted at the end. The
      questionnaire B concerned the personal point of view of pregnant women about the
      obtained information [2]. RESULTS: The results of the first two questionnaires
      (questionnaire A) are shown in Graph with a quantity of correct answers expressed
      in percents. The results of the questionnaire B are formulated according to
      answers to a question with "YES" and "NO", and they are expressed in percentage.
      The following results were obtained for questionnaire B: A hundred percent of
      pregnant women stated that they had learned something new about oral health, 67
      percent had immediately changed their nutrition for healthy food, 100 percent of
      them understood well the significant role of fluor prophylaxis, 16 percent did
      not accept it for unknown reasons, but 100 percent thought that it was very
      useful to hear lectures about oral health [3]. DISCUSSION: A great interest
      existed for all preventive stomatologic measures and dental procedures during
      pregnancy, which formerly, as a rule, were avoided because of ignorance [4]. It
      is necessary to carry out a proper prevention, and adequately inform and motivate
      pregnant women, so that we could have a satisfied mother and carefree child in
      the future.

PMID- 9265240
TI  - [Continuous ambulatory blood pressure measurement--a new method for the detection
      of arterial hypertension in children].
AB  - Blood pressure measurements obtained in a physicians office may not reflect the
      patients blood pressure during the whole day. Ambulatory blood pressure
      monitoring provides information about blood pressure during normal daily
      activities and night sleep. Further, the results of ambulatory blood pressure
      monitoring are in excellent correlation with end-organ damages. The paper
      discusses the chronobiology of blood pressure, the clinical use of ambulatory
      blood pressure monitoring, including the identified patterns of blood pressure,
      the correlation with end-organ damage and its use in clinical trials of
      antihypertensive medications.

PMID- 9265241
TI  - [Modern treatment of keloids].
AB  - Keloids are a benign proliferative growth of dermal fibrous tissue, usually
      resulting from an excessive tissue response to skin trauma or disease in
      predisposed individuals. The basic cause is unknown. Hypertrophic scars are
      similar lesions but they will, in time, show some degree of resolution. These
      lesions can be aesthetically disfiguring and cause functional disturbances. This
      paper reviews current knowledge of the treatment modalities for keloids and
      hypertrophic scars. Most physicians emphasize the importance of prevention. No
      single therapeutic modality is the best. Current various treatment options of
      keloids and hypertrophic scars are: surgical treatment, radiation, medicamentous
      treatment, treatment by mechanical pressure, and laser therapy, each alone and in
      various combinations. The published recurrence rates for keloid treatments vary
      widely, although they are the lowest for the combination of surgery and
      radiation, but other measures may be useful. Some keloids and hypertrophic scars
      may respond to intralesional triamcinolone and verapamil, but results were
      significantly better in early lesions. Clinical trials of intralesional
      administration of gamma-interferon, as well as topical application of retinoids
      have caused reductions in keloids. Pressure treatment is widely accepted. Laser
      therapy which selectively injures cutaneous microvessels without inducing scars
      may be successfully used in the treatment of keloids and hypertrophic scars.

PMID- 9265242
TI  - [The national program for the early detection and treatment of premalignant and
      malignant diseases of the lower genital system in women].
AB  - Lower genital tract malignancies are often seen in our female population; their
      detection is often delayed and treatment fails frequently. Latest scientific data
      on their etiology and newer methods of their detection and treatment in the early
      stages opens roads in the field of primary and secondary prevention and for the
      effective therapy, as well. In order to improve current status of the women's
      health in this field, on October 10, 1995 year, the Section for cervical
      pathology and colposcopy in addition to Yugoslav Association of Gynecologists and
      Obstetricians (UGOJ), has been established. One of the most important aims of the
      Section is introduction of premalignant and malignant diseases of female lower
      genital tract. So far, the Section has: 1. Submitted the Program proposal to the
      Ministry of Health of Serbia; on the basis of that proposal, on April 10, 1996
      year, the Ministry issued: "Expert instruction for the conduction of assignments
      aimed at early detection of the cancer of the uterine cervix". In that act
      obligatory for all health institutions, that have gynecology depts, all
      activities and goals for National Program introduction are prescribed. 2. The
      Yugoslav School for pathology of the cervix, vagina, vulva and colposcopy, opened
      in 1996, year, under the patronage of the Ministry of Health of the Republic
      Serbia provides the theoretical and practical training for the Program carriers
      and medical doctors receiving their training in gynecology and obstetrics. The
      first generation, the School attendees consisted of 149 doctors from the entire
      country. 3. Creation and submission of a draft common Health Form intended for
      the computerized and professional use, to provide for more efficient introduction
      of the National Program. The Form, should be introduced by the Health Ministry as
      an Official Health Document, to be used by all OBG institutions. 4. Submitted
      proposal of the activities and tasks in the field of Program realisation
      according to Health institutions' profiles. 5. Creation of the draft Protocol for
      actual activities and procedures in order to provide for an early detection and
      treatment of premalignant and malignant diseases of the female lower genital
      tract. Having the future mandatory character of this Protocol, the Section will
      divulge it to the professional audience. 6. Created a project of the National
      program and submitted it at the beginning of 1996 year, to the Republic Bureau of
      Health protection, with a request for its financial support in that program. In
      addition to the activities mentioned, the section management undertook and is
      taking measures for faster achievement of the aim-of the National Program
      introduction. Official Health institutions are assigned responsibilities of the
      Program introduction, the funding and a resolve all the legal, organisational and
      financial issues. Results that we are expected from this Program include
      introduction of the primary and secondary measures aimed at disease prevention;
      early detection of the diseases and its treatment; reduction of the numbers of
      cases in the advanced stages; significant improvement of gynecological status,
      and reduction of costs of the treatment of advanced stages of disease. The
      results should stimulate all, and become must for all subjects involved in the
      National Program realisation. The Program introduction into the daily OBG
      practice is a prerequisite of already well established practice in a number of
      countries, saving life and limb of most women affected by the lower genital tract
      malignancies.

PMID- 9265243
TI  - [Surgery in mitral stenosis].
AB  - Commissurotomy of a stenotic mitral valve on the closed heart was the beginning
      of the cardiosurgery. It helped hundreds of thousands of patients. At present in
      mitral stenosis surgery with extracorporeal circulation is recommended. The idea
      to eliminate the stenosis of the mitral valve by the closed route was adopted in
      percutaneous transvenous commissurolysis. The author discusses the submitted
      paper the development of mitral stenosis surgery at the cardiosurgical department
      in Hradec Kralove during 45 years since the first commissurotomy implemented in
      1951 by academician Bedrna.

PMID- 9265244
TI  - [Results of open valvotomy in congenital stenosis of the aortic valve].
AB  - Between 1977 and 1992 at the Cardiosurgical Clinic of the Faculty Hospital in
      Hradec Kralove on account of congenital valvular aortic stenosis 142 patients
      were subjected to catheterization. Valvotomy of a stenotic aortic valve was
      performed in 69 patients. The submitted paper evaluates the progression of aortic
      stenosis based on investigations of the aortic gradient and the area of the
      aortic orifice in repeatedly catheterized patients before and after valvotomy and
      evaluates also the results of surgery after a 1-15-year interval after surgery.

PMID- 9265245
TI  - [Aneurysms of the abdominal aorta].
AB  - The authors present the experience of the Plzen department with treatment of
      aneurysms of the abdominal aorta (AAA) during the last five-year period (1992
      1996) when they operated a total of 111 AAA in patients with an average age of
      67.9 years (44-91 years). The number of symptomatic AAA was 15 (13.5%), 36
      ruptures (32.4%). The most frequent risk factor was ischemic heart disease (IHD)
      in 74 (66.7%) and hypertension in 47 (42.3%) of the patients. Within 30 days
      after surgery two asymptomatic patients died (3.9%) and three (20%) with
      symptomatic AAA. The most frequent cause of death was acute myocardial infarction
      (AIM) in four (80%). Of 36 patients with rupture of AAA 17 (47.2%) died. A
      statistically significant factor for death of patients with rupture of the AAA
      was sever shock (blood pressure < 40 mm Hg) before surgery (p < 0.01), blood in
      the abdominal cavity (p < 0.01) and hypertension in the patient's case history (p
      < 0.05). Aimed screening of AAA in patients of risk groups and early elective
      surgery are important for reducing the incidence of ruptures of AAA. A patient
      with rupture of the AAA needs surgery urgently and unnecessary examination (CT,
      USG) frequently causes delay and reduces the patient's chance of survival.

PMID- 9265246
TI  - [Marginal indications for revascularization in the aortoiliac region].

PMID- 9265247
TI  - [Personal experience with radical treatment of varicose veins in the lower
      extremities, the present status and future perspectives of therapy].
AB  - In 1989-1993 at the Surgical department of the Central Military Hospital 815
      patients were operated on account of primary and relapsing varicosities of the
      lower extremities. Based on evaluation of the therapeutic outcome, after radical
      surgery very satisfactory short-term as well as long-term results can be expected
      with a low incidence of relapses of the disease. The operation assumes a careful
      diagnosis of the affection, radical surgery with regard to the cosmetic effect
      incl. treatment of all affected veins of the lower extremities.

PMID- 9265248
TI  - [Laparoscopically assisted iliofemoral bypass].
AB  - The author presents the case-history of a patient with obliteration of the
      arteria ilica externa, who was indicated for an ilicofemoral bypass with a
      prosthesis. The proximal part of the operation incl. the anastomosis was
      performed laparoscopically. This operation indicates the trend of future
      development of mininvasive surgery.

PMID- 9265249
TI  - [Contemporary views on thyroid gland surgery].
AB  - The authors reflect on changes in the approach of surgeons to patients and
      operations of the thyroid gland in recent years and emphasize those elements
      which they had favourable experience in recent years.

PMID- 9265250
TI  - [Portal vein thrombosis after splenectomy].
AB  - Elective splenectomies in haematologic malignancies are associated with two
      serious risks: infection and thrombotic complications. The case of a patient
      operated on for chronic lymphatic leukaemia with subsequent postoperative portal
      vein thrombosis is described. The complication was detected using abdominal
      ultrasonography and was treated successfully with anticoagulants (Fraxiparin).

PMID- 9265251
TI  - [Treatment of postoperative mediastinitis with sucrose].
AB  - The authors describe the treatment of postoperative mediastinitis in
      cardiosurgery by the open method with local sucrose administration and subsequent
      delay of closure of the thorax. Universal antibacterial properties of sucrose are
      made use of. Sucrose dissolves in the wound in its crystalline form and creates a
      medium with low aqueous activity (high osmolarity), which inhibits bacterial
      growth. The wound is rapidly cleansed, the secretion from the wound is within 10
      days bacteriologically negative and the chest can be closed secondarily. Simple
      resuture of the wound was performed four times, a plastic operation using the
      pectoral muscles twice and in one instance it was closed by a plastic operation
      of the transposed rectus abdominis muscle. The method was used successfully in
      seven patients.

PMID- 9265252
TI  - [Hematologic indications for splenectomy in childhood].
AB  - In 1988-1994 at the Pediatric Surgical Clinic, Faculty Hospital Motol splenectomy
      was performed in 66 children. Indication for splenectomy were haematological
      diseases (52), malignant and benign tumours (12) and congestive splenomegaly
      associated with cytopenia (2). The group does not comprise patients operated on
      account of injury. The most frequent haematological indications of splenectomy
      include haemolytic anaemia, chronic idiopathic thrombocytopenic purpura,
      hypersplenism and other conditions (haematological malignancies). The
      investigation is focused on haematological indications of splenectomy in
      childhood and its effect on treatment of the basic disease. Splenectomy on
      account of hereditary spherocytosis was performed in 31 patients. In all after
      surgery normalization of the haemogram was recorded. Of 11 patients, who were
      operated on account of idiopathic thrombocytopenic purpura (ITP) in nine
      normalization or marked elevation of the number of thrombocytes was observed. In
      two patients the rise of thrombocytes was slight however haemorrhagic
      manifestations of the disease receded. One patient operated on account of
      thrombocytopenia linked to the X chromosome died. In nine patients operated on
      account of other haematological indications after splenectomy improved values of
      the haemogram were observed. The immune state of the patients was not
      investigated.

PMID- 9265253
TI  - [Enzyme therapy in the treatment of lymphedema in the arm after breast carcinoma
      surgery].
AB  - The authors evaluate the contribution of proteolytic enzymes used in the
      treatment of the lymphatic oedema of the arm after mastectomy and radiotherapy
      for breast cancer. Proteolytic enzymes were successfully administered in
      monotherapy of lymphatic oedema as well as supportive therapy in other
      therapeutically ways.

PMID- 9265254
TI  - [An unusual complication of establishing a capnoperiteoneum for laparoscopic
      cholecystectomy].
AB  - The authors describe the case history of a female patient indicated for
      laparoscopic cholecystectomy. In the patient with progressing muscular dystrophy
      and thickening of the peritoneum it did not prove possible to establish a
      capnoperitoneum at the onset of the operation.

PMID- 9265255
TI  - [Metal stents in patients with malignant and benign stenoses of the biliary
      tract].
AB  - The authors summarise their experience with the treatment of almost 100 patients
      with malignant or benign stenosis of the biliary pathways by a percutaneously
      inserted expansible metal stent. They compare the advantages of different
      percutaneous procedures and evaluate critically indication for the introduction
      of an expansible metal stent or self-expansible stent in patients with malignant
      or benign stenosis of the bile ducts.

PMID- 9265256
TI  - [Development of guidelines in radiation oncology].
AB  - BACKGROUND: On a national and international level many scientific and health
      political efforts are undertaken to develop specific guidelines for various
      medical disciplines. They are thought to improve the transparency of the medical
      health system and guarantee an improvement and special care for the individual
      patients. Besides other medical disciplines radiation oncology also has to
      develop and establish such guidelines. METHODS: After a specific definition of
      the different terms "standard", "guidelines" and "recommendation" a general
      description of the principle process involved in the development of guidelines is
      given. Furthermore, the current activities of the special working group "Quality
      Control in Radiation Oncology" of the German Radiation Oncology Society are
      elaborated. RESULTS: A detailed set of guidelines is expected to be completed by
      the end of 1997.

PMID- 9265257
TI  - [Lung cancer--hopelessness in inoperability? A 10-year follow-up].
AB  - BACKGROUND: According to reports of Durrant et al. [19] and Berry et al. [5] it
      was concluded that non-operable non-small cell lung tumors cannot be cured. In
      this consequence initiation of radiotherapy was fixed at the beginning of
      symptoms. However, long-time survivors in our follow-up lead us to analyse not
      only quality of life and secondary therapeutic effects but also this special
      group with the results of the whole collective treated in the same period of
      interest. PATIENTS AND METHODS: Between 1.1. 1981 and 31. 12. 1983 a number of
      169 patients had been recommended for locoregional radiotherapy treatment of lung
      cancer; 145 patients received at least 50 Gy, 134 out of them 60 Gy or more.
      Men/female ratio was 137:8, median age was 65 (36 to 88) years. Classified
      according to the TN-stage there were 59 patients in T1-4 N0 and 86 patients in T1
      4 N1-3 M0. Histologically: 98 squamous cell carcinomas, 23 adenocarcinomas, 9
      large cell carcinomas and 15 specimens mixed from the named subgroup or rare
      histologies. Treatment concept including repetition of bronchoscopic evaluation
      after 60 Gy was prospectively discussed and fixed with our pneumologist.
      Radiation dose was given with a shrinking-field technique to mediastinum and
      primary. In case of macroscopically or microscopically persistence of tumor we
      continued radiation dose up to 80 Gy. Radiotherapy was not followed by
      chemotherapy. A telecobalt unit has been used for treatment due to the lack of
      high-voltage linear accelerators. In absence of a computer assisted planning
      system-a problem in most of the radiotherapeutic centers in this time-dose
      calculation was done by central beam planning of ICRU-point in the middle of the
      tumor respectively the center of target volume on the base of a cross section.
      Usually there was used a 3-field plan ap/pa opposite and an oblique field with an
      angle of 30 degrees from the ipsilateral back or ventral side, depending on the
      position of the tumor. Spinal cord was shielded to avoid a dose-more than 36 to
      42 Gy. The longer distance and higher weightiness of the oblique fields had as
      consequence lung fibrosis in the irradiated lung area and a considerable higher
      maximal dose situated in the soft tissue and skin often followed by strong
      indurations in this area 1 to 3 years after radiation therapy without further
      limitations of quality of life. RESULTS: From 145 patients with non-small cell
      lung cancer 64.1% (93/145) survived 6 months, 42.8% (62/145) 1 year, 19.3%
      (28/145) 2 years and 7.6% (11/145) 5 and 4.8 (7/145) more than 10 years.
      According to TN-stages T1-4 N0 collective had a survival rate of 67.8% (40/59)
      after half a year, 50.8% (30/59) after 1 year, 23.7% (14/59) after 2 and 11.9%
      (7/59) after 5 years. Treatment results by patients with positive lymph nodes T1
      4 N1-3 after the same intervals are: 61.6% (53/86), 37.2% (32/86), 16.2% (14/86)
      respectively 4.7% (4/86). In the period 5 to 10 years after irradiation 4
      patients died, 1 with local relapse, 2 with contralateral lung cancer-ipsilateral
      region was endoscopically and histologically free of tumor- and 1 patient in
      consequence of heart insufficiency of several years. Seven patients are still
      alive after 13 to 16 years. There is no sign of tumor in this group or any
      effects limitating their quality of life. Twenty-four patients received less than
      50 Gy. All patients but 2 did not survive 6 months. One patient survived half a
      year and 1 patient 2 years. CONCLUSIONS: The reported treatment results in a
      period with modest technological possibilities, a telecobalt unit, should
      encourage to a curative intention, when dissemination cannot be proved. If lung
      cancer is limited to the primary region with or without lymph node metastases the
      possibility of tumor elimination is small but feasible. If inoperable lung cancer
      is not curable, this mostly is not due to inability of locoregional radiotherapy,
      but rather can be seen as a lack of reliable and permanent elimination or
      prevention of

PMID- 9265258
TI  - [Therapy pf cervical lymph node metastases of unknown primary tumor].
AB  - BACKGROUND: The primary tumor remains unknown in approximately 3 to 9% of
      patients with lymph node metastases in the neck. Management of these patients is
      still controversial particularly because of the commonly as poor assessed
      prognosis. The treatment outcome was surveyed by a retrospective analysis, trying
      to identify prognostic factors. PATIENTS AND METHODS: From 1979 through 1993, 64
      patients with metastatic carcinoma of unknown primary tumor involving neck lymph
      nodes were treated. Most of them (n = 40) were squamous cell carcinomas. Forty
      eight patients underwent surgical resection of the involved nodes by neck
      dissection or excisional biopsy. Surgery was performed in 41 patients before and
      in 7 patients after radiotherapy. Additional chemotherapy was administered to 12
      patients (simultaneously to 11 patients). The irradiated volume included both
      sides of the neck, the supraclavicular region and the whole pharynx. The mean
      radiation dose was 59 Gy. In 32 patients, an additional boost to epipharynx (n =
      23) and/or large lymph nodes (n = 11) was given (mean: 12 Gy) by external beam
      therapy, in 2 cases by interstitial implants (22 Gy). Mean follow-up time was 8
      years (range: 7 months to 15 years, median: 9 years). RESULTS: Fifty-two out of
      64 (81.2%) patients came into a complete remission and 12 into a partial
      remission. The cause specific survival after 5 years for the whole group was 51.0
      +/- 7%, the overall survival 38.8 +/- 7%. Within the irradiated area the tumor
      control was 68.3 +/- 7%, the distant metastatic-free survival 70.0 +/- 7%. Best
      results showed patients after surgery+radiation (n = 48) with 67% overall
      survival at 5 years versus 0% (median: 9.2 months) without surgery (n = 16), and
      patients with lymph nodes located above the glottic level (n = 49) 63.2% versus
      9.0% (median: 1.2 years, n = 12). The primary tumor appeared in 9 patients (4
      times above the clavicles), once in the irradiated volume. CONCLUSION: Patients
      with cervical metastases of unknown primaries do not fare worse than patients
      with advanced carcinoma of head and neck and should be treated with a curative
      intent preferably by surgery and radiotherapy.

PMID- 9265259
TI  - [Pneumonitis after radiotherapy of bronchial carcinoma: incidence and influencing
      factors].
AB  - BACKGROUND: The most important side effect in radiotherapy of lung cancer is
      pneumonitis. The incidence of pneumonitis was evaluated in a retrospective study
      in the patient collective of the University of Heidelberg. Therapy related and
      therapy independent factors have been evaluated. PATIENTS AND METHODS: In 348 of
      392 cases with lung cancer who were treated by local irradiation between January
      1989 and January 1992 the patient's records were evaluable for response and
      toxicity. All patients were treated by megavolt equipment with a conventional
      fractionation in most cases. Standard target volumes were irradiated including
      the lymphatic drainage. From a dose of above 30 Gy a technique sparing the spinal
      cord was chosen. Retrospectively pneumonitis was classified into 4 grades
      starting from slight symptoms to respiratory insufficiency requiring O2. Grade I
      and II were summarized to slight, grade III and IV to severe pneumonitis.
      RESULTS: Regarding the treatment prior to irradiation patients with primary
      irradiation were affected in 26.5% (17% slight, 9.5% severe), with postoperative
      irradiation in 14% (9.3% slight, 4.7% severe), with radiochemotherapy of small
      cell lung cancer (SCLC) in 15.4% (12% slight, 3.4% severe) by this side effect.
      These differences were not significant (p = 0.32). The median onset of
      pneumonitis was 31 days after end of irradiation (severe 23 days, slight 44 days,
      p = 0.026). By a univariate analysis the total dose at the prescription point was
      the most important factor (30 to 50.5 Gy 11%, 52 to 59 Gy 15%, 60 to 74 Gy 26%, p
      = 0.007). High single doses (2.5 Gy) were only applied within a study of
      radiochemotherapy with a randomised sequential and alternating schedule. So that
      the increased rate of pneumonitis (42%) is not clearly separable from other
      influencing variables. A correlation between the applied techniques and the
      irradiated volume (measured by planimetric methods) was not demonstrable.
      Regarding the independent factors a high age, female sex and a low FeV1 were
      unfavourable. However, age and sex corrected FeV1 was not predictive.
      CONCLUSIONS: The observed incidence is within the range of literature. By a
      clinical point of view the total dose is an obvious factor. Also single doses
      above 2 Gy have to be seen critically (a total dose of 50 Gy). The results
      confirm the fact that patients with a low FeV1 are not suitable to a high dose
      irradiation of the chest. In this connection old patients and women also should
      be seen as patients at risk.

PMID- 9265260
TI  - [Intratumor pO2, S-phase fraction and p53 status in cervix carcinomas].
AB  - PURPOSE: Investigation whether tumor tissue oxygenation is influenced by
      proliferation or p53-status in cervical cancers. MATERIAL AND METHODS: From April
      1995 through December 1996, 28 patients with locally advanced cervical cancers
      (age 36 to 78 years; FIGO stages: 10 patients IIB, 16 patients IIIB, 2 patients
      IVA) underwent intratumoral measurement of pO2 prior to definitive radiotherapy.
      The histological specimens were examined for grading and quantitative
      immunohistological expression of the MIB-antigen and p53-protein. Proliferation
      was estimated by measuring the S-phase fraction with flow cytometry. RESULTS: The
      median pO2-values showed a broad variation from 2.2 through 60.4 mm Hg, median
      19.7 mm Hg. The S-phase fraction varied from 4.2 through 34.2% (median 11.6%),
      MIB-positive cells from 20 through 100% (median 74%), and immunohistologically
      p53-positive cells from 0 through 95% (median 2%). The patients were divided in 2
      groups according to the pretreatment pO2. Tumors with a pO2 above the median had
      a lower S-phase fraction than tumors with a pO2 below the median, 10.4 +/- 3.8%
      versus 16.3 +/- 5.5%, p < 0.02. MIB and p53 were not different in both groups
      (MIB: 68.1 +/- 27.7% versus 75.0 +/- 18.4%, p = 0.1; p53: 26.4 +/- 38.5% versus
      18.1 +/- 19.8%, n. s.). Grade of differentiation and FIGO stage had no impact on
      pO2. CONCLUSION: Locally advanced cervical cancers with a poor oxygenation have a
      higher proliferative activity. Tumor proliferation may play a causative role for
      the development of hypoxia as suspected from radiobiological theories.

PMID- 9265261
TI  - [Increasing incidence and declining mortality in breast carcinoma].

PMID- 9265262
TI  - [Hypoxia-mediated selection of p53-mutated cells].

PMID- 9265263
TI  - [Does tamoxifen have a negative effect on survival chances of premenopausal women
      with locoregional recurrence of breast carcinoma?].

PMID- 9265264
TI  - [Regional differences in health care services. What is needed for a more unified
      practice?].

PMID- 9265265
TI  - [Routine ultrasonography in obstetric care].

PMID- 9265266
TI  - [Prevention--are we not good enough?].

PMID- 9265267
TI  - [When the heart is failing and the donor is missing].

PMID- 9265268
TI  - [Extracorporeal heart pump--a bridge to heart transplantation. First Norwegian
      experiences].
AB  - By February 1997, the number of heart transplantations at the National Hospital
      had reached 265. In our department, the first bridge to transplantation in using
      Thoratec artificial heart was performed in 1995. A 44 year-old patient with life
      threatening heart failure was placed for one week on cardiopulmonary assist with
      an intra-aortic balloon pump and a veno-arterial cardiopulmonary bypass. Due to
      unceasing heart failure a Thoratec left ventricular assist device was implanted
      as a bridge to transplant. The patient was successfully transplanted two days
      after implantation of Thoratec. After eight months follow-up he is in New York
      Heart Association (NYHA) functional class I. Another patient, 17 years of age,
      and with dilated cardiomyopathy, went into cardiogenic shock while awaiting heart
      transplantation. For three days he had cardiopulmonary assist with intra-aortic
      balloon pump and venoarterial bypass with an oxygenator. After seven weeks on the
      left ventricular assist device he was transplanted. Although one episode of
      severe rejection occurred, be is in NYHA functional class I after four months
      follow-up. Our early experience is encouraging. Ventricular assist devices should
      be considered as a life support for patients scheduled for heart transplantation
      and expected to die within a very short time.

PMID- 9265269
TI  - [Myocardial infarction in young patients. Consequences of routine coronary
      angiography].
AB  - The value of coronary angiography in unselected patients after myocardial
      infarction is still controversial. Our study includes 131 consecutive young
      patients (< 50 years old) in whom coronary angiography was performed after their
      first myocardial infarction. Angina pectoris was present in 71 (54%), and silent
      ischemia in 11 (9%): 49 patients (37%) were asymptomatic and without myocardial
      ischemia. Significant coronary artery stenosis was present in 119 patients (91%).
      A larger share of the patients with angina or silent ischemia than of those
      without had multivessel disease and high angiographic risk, and more of them were
      referred for revascularization. However, many of the asymptomatic patients with a
      negative result on the exercise test also had serious, high risk coronary heart
      disease, and needed revascularization. Thus, although the presence of angina or
      myocardial ischemia can identify a group of patients with serious coronary heart
      disease, the diagnostic precision is low, and if coronary angiography is not
      performed, many young patients with high risk disease may be overlooked.

PMID- 9265270
TI  - [Infarction in the inferior myocardium with and without damage to the right
      ventricle. Treatment and prognosis].
AB  - Acute inferior infarction often involves the right ventricle as well. For these
      patients, the prognosis is not as good as for patients with inferior infarction
      alone. Right ventricular infarction can be diagnosed with a high level of
      sensitivity and specificity by recording right precordial leads. We used V4R. 100
      patients admitted to the Coronary Care Unit with an electrocardiographic
      diagnosis of inferior infarction were registrated consecutively. V4R was recorded
      in 95 patients; the right ventricle was affected in 35 of them. The mortality
      during the stay in hospital was 3% in the group with inferior infarction and 11%
      when the right ventricle was involved (p > 0.05). An unusually large proportion
      of the patients in both groups received thrombolytic therapy (more than 70%). The
      result may indicate that thrombolytic therapy is of particular benefit to
      patients with inferior infarction and involvement of the right ventricle.

PMID- 9265271
TI  - [Check up on pacemaker patients. Experiences with long intervals between check
      ups].
AB  - The effect of pacemaker follow-up during the second to fifth year post
      implantation has been studied. 230 selected patients with single chamber
      pacemakers (SSI) were followed up at intervals of 2-4 years and were observed
      prospectively. 110 dual chamber (DDD) and 121 rate-responsive single chamber
      pacemakers (SSIR) were evaluated retrospectively. In the observation period 7
      SSI, 11 DDD and 2 SSIR were reoperated, 8 SSI, 40 DDD and 26 SSIR were
      reprogrammed. The majority of the interventions were patient-initiated and not
      the result of routine follow-up. 13 sudden deaths were reported, none of them
      proven to be pacemaker-related.

PMID- 9265272
TI  - [Coil embolization of persistent ductus arteriosus].
AB  - From September 1994 to January 1996, 57 patients were admitted to Brompton
      Hospital for catheter closure of persistent ductus arteriosus. Umbrella closure
      was attempted in 22 patients and coil closure in 35. The duct was closed by a
      device in 55 of 57 patients (96.4%). Two patients were referred for surgical
      closure, one after failure of the umbrella closure and one after coil
      embolization to a branch of the pulmonary artery. Two additional coils embolized
      to pulmonary artery branches. Both coils were successfully retrieved by a snare,
      and the procedure then finished successfully. We recommend the use of coils for
      closure of small ducts, and for residual leak after previous umbrella closure.
      This is also a promising method for closure of larger ducts.

PMID- 9265273
TI  - [Routine ultrasonography in obstetric care in Norway, 1994].
AB  - The article reports on a national cross-sectional study of the use of ultrasound
      in obstetrics. Seven of the 65 obstetrical units in the country did not
      participate. The material consists of information from 1,091 consecutive
      deliveries in the course of one week. Only 14 of the women (1.3%) had not been
      examined with ultrasound during pregnancy, 97.8% had had a routine examination
      before week 20. Most of the women (46%) had had only one examination; the mean
      number of examinations performed per woman was 2.2. Only three small obstetric
      units were unable to offer screening to their patients. Approximately 98% of all
      pregnant women are now offered a routine examination at their local department of
      obstetrics. The way obstetric ultrasound is practised has become more consistent.
      Fewer women in this study than in previous studies had more than one examination,
      and a larger share were screened before week 20. The mean number of examinations
      performed per woman has not changed since 1988.

PMID- 9265274
TI  - [Serous meningitis associated with primary genital herpes infection].
AB  - Aseptic meningitis is not an uncommon complication to primary genital herpes
      infection caused by herpes simplex virus type 2 (HSV-2). Compared with other
      types of viral meningitis, HSV-2-meningitis is associated with a significant rate
      of neurological complications in the acute stage. In addition, some patients will
      suffer from recurrent aseptic meningitis (Mollaret's meningitis) later. We
      describe six patients, five women and one man, age 26-35 years, with aseptic
      meningitis caused by HSV-2. All the patients showed serological evidence of
      primary herpes infection (negative HSV-IgG and/or positive HSV-IgM in serum
      samples). Polymerase chain reaction detected HSV-2 in cerebrospinal fluid in all
      five of five cases, while virus cultures were positive in two of the six cases.
      Only three patients showed clinical signs of simultaneous genital herpes
      infection. One patient, a 28-year-old female, developed transient autonomic
      nervous system dysfunction with urinary retention, constipation, and neuralgic
      pain in the buttocks, perineum and lower limbs. 13 months later she was
      hospitalised for a genital herpes infection with headache, parestesia and fever,
      but spinal fluid examination showed no abnormality.

PMID- 9265275
TI  - [Mollaret meningitis. Is the riddle finally solved?].
AB  - Mollaret's meningitis is characterised by recurrent aseptic meningitis in
      otherwise healthy persons. It has recently been shown that most cases are caused
      by herpes simplex virus type 2 (HSV-2). In this article we describe five women,
      age 33-57 years, with altogether 12 episodes of virus-culture negative aseptic
      meningitis, where polymerase chain reaction detected HSV-2 in samples of
      cerebrospinal fluid. Only three patients had a medical history of previous
      genital herpes infection. None of our patients has been offered prophylactic
      antiviral treatment.

PMID- 9265276
TI  - [Regional differences in the use of coronary angiography in the examination of
      heart patients].
AB  - We monitored, for a period of 26 months, the use of coronary angiography at a
      catheterisation laboratory serving a Norwegian county with two distinct
      geographical regions, each with one referring hospital. Catheterisation was used
      twice as often in the one region as in the other. The patients from both regions
      belonged to the same angina function class at referral, and there was no
      significant difference in the findings at angiography or the need for coronary
      angioplasty and coronary artery bypass grafting. The incidence of coronary artery
      disease and the availability of coronary angiography was also the same in the two
      regions. The main reasons for the different rates of use are a more liberal
      referral policy in the high rate region, and less access to specialists in the
      low rate region.

PMID- 9265277
TI  - [Cardiovascular risk factors in persons aged 40-42 years in the county of Hedmark
      1988-94].
AB  - We present the results from three surveys conducted in 1988, 1991 and 1994 in
      Hedmark comparing risk factors for cardiovascular disease among men and women age
      40-42 years. The data are compared with the results for persons in the same age
      group from the counties Vestfold, Rogaland and Nordland, and examined in the same
      periods. In 1991 the average levels of total cholesterol and infarction risk
      score were the same in Hedmark and the three other counties, but in 1994 Hedmark
      compared less favourably. While the mean levels of total cholesterol showed
      minimal difference between rural and urban municipalities in Hedmark,
      triglycerides and systolic blood pressure were higher in the rural areas.
      Adjustment of the results in Hedmark for lower attendance rate among unmarried,
      divorced and widowed persons in 1991 and 1994 than in 1988 does not affect other
      risk factors than smoking. We discuss possible explanations of the less
      favourable results and the implications for primary prevention of cardiovascular
      diseases.

PMID- 9265278
TI  - [Calcium channel blockers in heart failure].
AB  - Patients with heart failure are particularly susceptible to the negative effects
      of calcium channel blockers because the failing heart demonstrates a defect in
      the delivery of calcium to the contractile proteins, and an attenuation of the
      normal sympathetic reflexes. Currently these drugs have no place in the treatment
      of heart failure caused by systolic dysfunction of the left ventricle. Calcium
      channel blockers should probably not be described for patients with coronary
      artery disease and left ventricular dysfunction. When the patient needs
      additional treatment for angina and beta-blockers or nitrates have not given
      satisfactory results, it may be appropriate to prescribe amlodipine or
      felodipine.

PMID- 9265279
TI  - [Induction of increased cardiac tolerance against damage--a new therapeutic
      principle?].
AB  - In animal experiments, brief periods of myocardial ischemia have shown to improve
      cardiac tolerance against a subsequent ischemic exposure. We argue that ischemic
      preconditioning may be only one example of a general protective biological
      adaption to harmful stimuli. We refer to several studies indicating that ischemic
      preconditioning may occur in patients, e.g. during episodes of angina pectoris,
      or during percutaneous transluminal coronary angioplasty or cardiac surgery. The
      phenomenon has also been demonstrated in cultured human myocytes after anoxic
      periods. In the future, therefore, it may be possible to use suitable drugs to
      induce higher ischemic tolerance in patients with cardiac disorders. It may also
      be possible to induce protection against other harmful stimuli. Extensive
      research is necessary, however, to reveal the underlying mechanisms and choose
      the most suitable procedures.

PMID- 9265280
TI  - [Patients with diabetes mellitus--secodary prophylaxis after myocardial
      infarction].
AB  - The mortality rate after myocardial infarction is more than twice as large in
      diabetic patients than in patients without diabetes. Optimal blood sugar control
      in the acute phase and during follow-up might improve prognosis. The relative
      reduction in mortality and cardiac events after myocardial infarction by means of
      betablockers, ACE inhibitors and statins is the same for diabetics as for non
      diabetes. However, because of the poorer prognosis, the absolute reduction in
      mortality is more than twice as high in diabetic as in non-diabetic patients. For
      this reason, diabetic patients comprise a target group for secondary prevention
      by means of betablockers, ACE inhibitors and statins after myocardial infarction.

PMID- 9265281
TI  - [Sudden cardiac death in hypertension].
AB  - Sudden cardiac death constitutes 10-20% of all deaths in the western world. In
      75% of the cases a coronary cause is found, and the risk of sudden cardiac death
      increases with advancing coronary heart disease. Hypertension is one of the main
      risk factors for coronary disease, and hence also for sudden death. The risk of
      sudden death is three times higher in patients with moderate hypertension than in
      normotensives. Compared with the survivors, those who die suddenly have higher
      blood pressure. In hypertensives, sudden cardiac death constitutes 27-60% of all
      cardiovascular deaths. This article focuses on hypertension as a risk factor for
      sudden cardiac death and discusses the options of primary prophylaxis.

PMID- 9265282
TI  - [Cholesterol lowering therapy after myocardial infarction. Consequences of the
      CARE study].
AB  - In the recently published CARE-study, 4,159 patients aged 21-75 years were
      included and randomised to treatment with pravastatin 40 mg once daily or placebo
      3-20 months following a myocardial infarction. Inclusion criteria were a total
      cholesterol < 6.2 mmol/l and LDL-cholesterol 3.0-4.5 mmol/l. Mean follow-up time
      was five years. Average reduction of total cholesterol was 20% and of LDL
      cholesterol 28% in the treatment group. The incidence of coronary death or non
      fatal myocardial infarction was reduced by 24% (p = 0.003). The cholesterol
      levels in the CARE-study were similar to those in most western populations and
      lower than in the 4S study. This must be considered when evaluating the different
      results of the treatment in the two studies. It seems fair not only to offer
      statin treatment to patients complying with the 4S inclusion criteria, but also
      to patients with values as in the CARE population.

PMID- 9265283
TI  - [Genetic information and counseling in psychiatry?].

PMID- 9265285
TI  - [Recruitment problems in medical research?].

PMID- 9265284
TI  - [Dynamic mutations--new light on Huntington disease].

PMID- 9265286
TI  - [Subarachnoidal hemorrhage--prophylactic possibilities].

PMID- 9265287
TI  - [Diabetes in pregnancy--without clinical significance?].

PMID- 9265288
TI  - [Are preventive consultations free of charge?].

PMID- 9265289
TI  - [Preventive measures in hospital].

PMID- 9265290
TI  - [Outpatient clinics].

PMID- 9265292
TI  - [The system of listed patients--a step back].

PMID- 9265291
TI  - [Shortage of scholarship recipients--a will to take action?].

PMID- 9265293
TI  - [Searching for alternatives].

PMID- 9265294
TI  - [Ecstasy--the way to ecstasy or despair?].

PMID- 9265295
TI  - [To be sick and having a disease].

PMID- 9265296
TI  - [Towards normalcy...].

PMID- 9265297
TI  - [Research on immigrants and health. Curiosity or benefit?].

PMID- 9265298
TI  - [Safety equipment and automobile accidents].

PMID- 9265299
TI  - [Air bags influence the pattern of injury in severe thoracic trauma].
AB  - Severe intrathoracic cardiovascular injuries were found in three patients who
      were drivers of cars involved in head on collisions causing air bags to be
      released. A 32 year old male had not worn a seat belt, while a 39 year old female
      was restrained by a seat belt. The male patient suffered an intimal lesion of the
      brachiocephalic artery. Extensive soft tissue haematomas were seen subcutaneously
      and retrosternally. The female suffered a rupture of the aortic isthmus and a
      dislocated pelvic fracture. Vascular repair was performed in both patients. The
      female died after two months without having regained consciousness. The third
      patient, a 47 year old male, had not worn a seat belt. He lost his pulse within
      minutes. Midline emergency thoracotomy showed a complete rupture of the right
      atrium. An air bag protects against injuries caused by hitting internal parts of
      the vehicle. It does not necessarily protect against deceleration trauma in high
      speed collisions.

PMID- 9265300
TI  - [Medical consultation about Pakistani immigrants. The pattern of consultations
      and diagnosis at a health center in Oslo].
AB  - The purpose of this study was both to ascertain the extent to which Pakistanis,
      compared with Norwegians, consult a doctor and to discover possible differences
      in the type of diagnosis received by the two groups, 6867 consultations where the
      patient was either Pakistani or Norwegian were registered over a period of one
      year at Stovner Health Centre. The frequency of the consultations differed more
      between men and women than between Pakistanis and Norwegians. On the whole the
      Pakistani patients received more symptom diagnoses and fewer diagnoses of illness
      than the Norwegians did, but here too there was a greater difference between the
      sexes than between the nationalities-women received most symptom diagnoses. Women
      practitioners gave symptom diagnoses more often than their male colleagues, did.
      Our study has shown that differences between the sexes are greater than
      differences between the races. This may help to break down barriers between "US"
      and "them".

PMID- 9265301
TI  - [Intercultural communication in general practice].
AB  - What is the reason for possible communication problems between physicians and
      immigrants from the third world? How is the interaction between the two groups
      regulated? To answer such questions, 15 doctors and 10 immigrants were
      interviewed about their experience of the doctor-patient interaction in
      unstructured open-ended interviews. Culturally based verbal and non-verbal
      expressions were particularly difficult to interpret, being based on different
      thought models and language. Owing to the world wide generalisation of the doctor
      patient roles the gap between the two "partners" in the communication has been to
      some extent bridged. Largely independent of the doctors' will, the immigrants
      assigned considerable authority to the doctors. Thus the power of the doctor is
      based on the institutionalisation of the more universal doctor-patient role.

PMID- 9265302
TI  - [Endemic typhus imported to Norway].
AB  - Murine typhus, caused by Rickettsia typhi, is an important zoonosis in all parts
      of the world. The disease is transmitted from rodents to humans by fleas. In this
      article we describe the first three cases of serologically proven murine typhus
      imported into Norway during the 1990s. The patients were Norwegian tourists who
      had visited respectively Guinea-Bissau, Crete and Thailand. They all became
      acutely ill with fever, chills and severe headache 1-10 days after return to
      Norway. None of them had a rash. Two patients were admitted to hospital, and one
      was treated with ciprofloxacin for suspected typhoid fever. All the patients
      recovered without sequelae. The diagnosis of murine typhus was based on detection
      of IgM-anti-bodies against R typhi in serum samples during reconvalescence.

PMID- 9265303
TI  - [Norwegian fibromyalgia epidemic--its rise or possible decline. What is the trend
      based on disability statistics?].
AB  - The Norwegian National Insurance Scheme (Folketrygden) offers universal coverage
      to all inhabitants between 16 and 67 years with respect to disability pension.
      During the 1980s, the number of new disability-pensioners increased rapidly. In
      1991, 8.5% of the population at risk received this pension. So called "diffuse"
      conditions in the musculoskeletal system accounted for a large proportion of new
      cases. Myalgia/fibromyalgia became a major reason for disability pension. In 1989
      more than 7% of the new cases had this diagnosis. The parliament (Stortinget)
      passed controversial amendments to the National Insurance Acts in 1991 and 1995
      which restricted the criteria for obtaining a disability pension. At present the
      law demands that "a scientific concept of disease" should be applied in these
      matters. The numbers of new disability-pensioners decreased significantly during
      the period 1989-1993. The figures from 1994 and 1995 perhaps show a new upward
      trend, including also "diffuse" diagnoses like fibromyalgia. The use of "diffuse
      conditions" as a cause for disability pension is discussed in light of the
      official request for a scientifically justified diagnosis.

PMID- 9265305
TI  - [Use of alternative medicine among Norwegian hospitalized cancer patients].
AB  - A national multi-centre study was performed to investigate the prevalent use of
      alternative medicine, or non-proven therapies, among Norwegian cancer patients.
      Of 911 patients invited to take part in the study 642 were included in the final
      analysis. Among the 630 assessable patients, 20% had been or were current users
      of non-proven therapies. In the northern most and western parts of Norway the
      most preferred alternative methods are healing by hand and faith healing, while
      herbs, vitamins, diets and Iscador are popular in the central and southern parts.
      Use of nonproven therapies is common in the northern part of the country.
      Prevalent users are middle-aged patients with long-standing symptomatic disease
      and former users of non-proven therapies for nonmalignant disease. About 40% of
      the patients would like non-proven therapies to be an option in hospital. Most of
      the users of non-proven therapies (80%) had consulted practitioners of scientific
      medicine first; 15% had started treatment with non-proven therapies
      simultaneously. The users of non-proven therapies report having received less
      hope of cure (30%) from their physicians than the non-users (50%) had. Most of
      the users had learned about non-proven therapies from friends or relatives. Most
      users believe that non-proven therapies might make them stronger and relieve
      their symptoms. Very few patients believe in a cure (10%). Nearly 40% felt that
      non-proven therapies had no definite effect on them. Four patients reported
      adverse effects. 15 patients had been treated abroad, usually in Denmark.

PMID- 9265304
TI  - [Chronic CO poisoning. Use of generator gas during the second world war and
      recent research].
AB  - The consequences of long-lasting and low-grade exposure to carbon monoxide are a
      matter of debate. During the second world war, lack of petrol led to widespread
      use of wood as fuel (generator gas vehicles), especially in the Nordic countries.
      This caused many cases of "acute" or "chronic" carbon monoxide poisoning. Typical
      symptoms of "chronic poisoning" were headache, dizziness and tiredness. Usually
      the symptoms disappeared after some weeks or month, but in some patients probably
      became permanent. The experiences from the generator gas era are now almost
      forgotten, and chronic carbon monoxide poisoning is easily overlooked. The
      authors describe two cases of such poisoning. A crane driver at a smelting works
      developed permanent symptoms after twenty years of exposure. A faulty oil-fired
      central heating system caused long-lasting symptoms in four members of a family.

PMID- 9265306
TI  - [Norwegian physicians and alternative medicine. Knowledge, attitudes and
      experiences].
AB  - 1272 members of the Norwegian Medical Association took part in a survey on
      knowledge about, attitudes towards and experience of acupuncture, reflexology,
      healing, homoeopathy and herbalism. The response rate was 91%. Knowledge about
      these five complementary methods of treatment was poor, particularly in regard to
      reflexology, healing and herbalism. Four out of five physicians, on the other
      hand, felt that they needed such knowledge to put them in a position to inform
      their patients. Furthermore, the physicians' attitudes were also fairly negative,
      except towards acupuncture. Only 4-11% regarded homoeopathy, reflexology or
      healing as valuable supplements to scientific medicine. 9% of the physicians had
      undergone acupuncture, and 4% practised this method. 65% referred their patients
      to acupuncture. Experience of the other four methods was less common. Poor
      knowledge and limited experience put Norwegian physicians in a weak position in
      the debate about complementary methods of treatment.

PMID- 9265307
TI  - [Research in alternative medicine. What is documented, and what is
      documentation?].
AB  - A study of the literature describing research on alternative medicine showed
      that, in general, the research was of poor quality. Any clinical effect of
      kinesiology had not been documented. Only few studies on reflexology had been
      controlled. Several controlled studies on healing showed significant effect,
      mainly in patients with psychosomatic disorders, or when the patient had great
      faith in the healer. Acupuncture seems to be effective against nausea, in
      patients with chronic pain and in patients who have had stroke. The data do not
      support the claim that acupuncture is effective for asthma or addiction. In the
      case of homeopathy the evidence from clinical trials is positive but not
      sufficient to draw a definite conclusion, for example, is it better than placebo?
      The majority of studies seems to disregard the principle of homeopathy, i.e. that
      the treatment should be individualised. Even if the documented effect of
      alternative medicine is not convincing, the effect is favourable empirically and
      may in itself be sufficient to give practitioners of alternative medicine an
      authorization. The term "alternative medicine" should be replaced by
      "complementary medicine".

PMID- 9265308
TI  - ["Earth rays"--an underground phenomenon?].
AB  - According to reports in the Norwegian lay press, a lot of illness can be ascribed
      to "earth rays". Earth rays are presumed to form a square pattern, but can only
      be demonstrated by dowsing. No documentation has been reported which supports
      their existence. However, many patients have experienced considerable relief
      after a protecting copper net has been placed under their beds. Four dowsers
      participated in an experiment where, independently of each other, they were to
      demonstrate the pattern of earth rays in a gymnasium. Four supervisors ensured
      that the dowsers could not communicate with each other during the experiment. As
      it turned out, they came up with four totally different patterns. Thus, any
      protective treatment prescribed by the dowsers seems to be based on pure chance.

PMID- 9265309
TI  - [Holistic health and specific disease].
AB  - Health and disease are cardinal concepts in all medical activity. There are two
      main theories of the conceptual structure of medicine. The reductionist theory
      defines the concept of disease as deviation of bodily or mental functions, while
      the holistic theory tries to establish a positive concept of health. The
      reductionist theory claims to be essensialistic, descriptive and objective, while
      the holistic theories are supposed to be nominalistic, normative and subjective.
      A presentation of the theories show that both positions involve conceptual
      difficulties.

PMID- 9265310
TI  - [Drugs and light].
AB  - The number of drugs that are found to be photochemically unstable or able to
      induce phototoxic side-effects is steadily increasing. It can be difficult,
      however, to obtain relevant information on the photoreactivity of drugs or drug
      products from the commonly used handbooks. This is because of lack of standard
      methods of evaluation or a requirement for official specifications for a given
      product. The author points to the main problems connected with interactions
      between drugs and light in vitro and in vivo. The most obvious result of exposure
      to light is reduced potency of the drug because of photodecomposition. Adverse
      effects due to the formation of photodegradation products during storage and use
      have also been reported. The drug substance can further cause light-induced side
      effects after administration to the patient, e.g. phototoxicity and photoallergy.
      More data on photoreactivity are needed in order to minimize the side-effects of
      frequently used drugs. The article includes a list of potential photosensitizing
      drug substances on the Norwegian market.

PMID- 9265311
TI  - [Phototherapy. An alternative for seasonal affective disorders or sleep
      disorders].
AB  - Although clinicians have observed for centuries that som depressed patients
      become worse in the winter, it was first in 1984 that Norman Rosenthal and co
      workers described a syndrome which they called seasonal affective disorder (SAD),
      characterised by winter depression, lethargy and a craving for carbohydrate.
      Phototherapy was proved to be an effective treatment right from the start.
      Recently it has been reported that not only depression, but also panic disorder
      and obsessive compulsive disorders may exhibit a seasonal pattern and thus
      benefit from phototherapy. Phototherapy may also benefit patients suffering from
      "sun-downing", a syndrome of confusion and agitation in the evening in persons
      with Alzheimer's disease. Based on the observation that bright light may both
      elevate brain serotonin and ameliorate sleep abnormalities, the authors report
      the results of phototherapy for treatment of non-seasonal depressions, either
      alone or in combination with antidepressants or sleep deprivation.

PMID- 9265312
TI  - [Phototherapy of jet lag, night work and sleep disorders].
AB  - Jet lag, complaints associated with night work, and certain sleep disorders may
      be caused by misalignment between the endogenous circadian rhythm and the
      sleep/wake cycle. The authors discuss how light influences and regulates the
      circadian rhythm. The endogenous circadian rhythm is generated by the
      suprachiasmatic nucleus, and the effect of light is mediated to this nucleus
      directly via the retinohypothalamic tract. The effect is dependent on the timing
      of the light exposure relative to the nadir of the endogenous rhythm, which
      usually is located at about 5:00 AM. Exposure to bright light before nadir
      induces a phase delay, whereas a phase advance is obtained with exposure to light
      after nadir. The paper describes how bright light treatment can be used to reduce
      the effects of jet lag and of night work, sleep phase disturbances and early
      morning awakenings. Melatonin administration is an alternative treatment for the
      same type of disorders, and is also discussed in the article.

PMID- 9265313
TI  - [Sedimentation rate and renal cancer].
AB  - This paper is based on two articles published in 1996 in Journal of Internal
      Medicine. One is an evaluation of the erythrocyte sedimentation rate (ESR)
      measured in 3910 subjectively healthy Norwegians of both sexes, with an age range
      of 20 to 90 years. The authors underline the difference between a population
      based and a subject-based upper ESR reference level, and the benefit of knowing
      each single healthy person's subject-based ESR level. The other article shows
      that, in 70% of a sample of 236 randomly selected patients with renal cell
      carcinoma, a diagnosis could have been indicated several years before clinical
      symptoms or signs became apparent. Therefore, the ESR might be a predictive test
      for many such cancer cases. This type of cancer has a good prognosis when treated
      surgically at an early stage. In Norway, 432 new cases occurred in 1993, 264 in
      men and 168 in women. If our observations are generally applicable, and proper
      attention had been paid to a slowly increasing ESR value over time, about 300 of
      these cases could have been operated on much earlier. It is suggested that
      physicians and public might both benefit from this knowledge.

PMID- 9265314
TI  - [The principles of homeopathy].
AB  - Homeopathy is a gentle but effective form of treatment which stimulates the
      natural ability of the organism to heal itself. The word homoeopathy comes from
      the greek words "homoios" which means similar, and "pathos" which means disease.
      This reflects the main principle of homoeopathy, the law of similars, which
      predicts that a disease can be cured by a medicine, which in healthy people is
      able to produce a condition that resembles the disease. The law of similars is
      probably a basic law of nature. Therefore it is not surprising that examples can
      also be found in orthodox medicine, where the mode of functioning for some
      medicines probably can be ascribed the law of similars. Homoeopathic medicines
      are likely to work through the body's own curative powers in a way that is best
      explained by comparison with vaccination. Both the homoeopathic medicine and the
      vaccine constitute a mild stimulous that causes mobilisation of the body's
      defence mechanisms and thus increased ability to oppose a pathogenic influence.
      The homoeopathic medicine does not work at molecular level, but probably through
      non-materialistic qualities (possibly electromagnetic in nature) in the organism,
      which are so sensitive that even a mild stimulus is enough to cause a reaction.
      This means that homoeopathic preparations can still have an effect even when
      diluted beyond avogadro's number.

PMID- 9265316
TI  - [From plan to chaos? Norwegian health care through 50 turbulent years].

PMID- 9265315
TI  - [Homeopathy--time for official authorization?].
AB  - The Norwegian government has recently appointed a committee to scrutinise
      alternative therapies and distinguish between serious and nonserious
      practitioners in preparation for future authorisation. Homoeopathy seems to be
      the most popular of alternative therapies in Norway, and counts Prime Minister
      Thorbjorn Jagland among contented patients. For this reason we have taken a
      closer look at the principles of homoeopathy, and the documentation. Just as in a
      recent report on documentation and the effect of selected alternative therapies,
      we too were unable to find studies of reasonable quality that were confirmed by
      others. Homoeopathists use theoretical physics to explain how water "remembers"
      the information from molecules no longer existing in the solution, when the
      liquid is shaken in a special way between every dilution. It does not matter
      whether the homoeopathist is serious or not as long as the remedy consists only
      of pure water. We conclude, therefore, that homoeopathy should not be authorised
      as a serious medical treatment in the Norwegian Health Service.

PMID- 9265317
TI  - [Little on ethics and liberal health policy].

PMID- 9265318
TI  - [Cardiac natriuretic peptides as markers of left ventricular dysfunction].

PMID- 9265319
TI  - [Chiropractic and treatment of back pain].

PMID- 9265320
TI  - [Homeopathy--too unbelievable to be true!].

PMID- 9265321
TI  - [Drugs for osteoporosis].

PMID- 9265322
TI  - [Patients listed for general practitioners].

PMID- 9265324
TI  - [A younger cardiologist on the Internet].

PMID- 9265323
TI  - [Cloning of sheep--and humans too?].

PMID- 9265325
TI  - [The influence of antihypertensive treatment on progression of chronic
      nepropathy].
AB  - This article describes the influence of antihypertensive treatment on the
      kidneys, both the acute and the long-term effects, especially with regard to the
      progression of chronic non-diabetic renal failure. Our knowledge about the
      different antihypertensive drugs is still limited, but some studies indicate that
      especially ACE-inhibition and perhaps calcium antagonism may have the potential
      to postpone renal failure.

PMID- 9265326
TI  - [Diet for heart patients. A questionnaire study at Danish coronary care units].
AB  - A questionnaire survey of Danish hospitals showed that 70% of patients admitted
      for acute ischaemic heart disease were served the ordinary menu during their stay
      at the hospital. About 10% had a diabetic menu, while 20% had different kinds of
      lipid lowering diets. The ordinary menu contained 17 energy percent (E%) protein,
      38 E% fat, and 46 E% carbohydrate. The amount of fibre was 3.1 g/MJ, the ratio of
      polyunsaturated to saturated fatty acids (P/S) was 0.4, and the total energy in a
      day's menu was 8.1 MJ. The ordinary high-fat hospital diets differ markedly from
      diets believed to be cardioprotective, contrast with the dietary counselling
      given during admission, and should be replaced by lipid lowering diets in most
      cases of acute ischaemic heart disease for educational and therapeutic reasons.

PMID- 9265327
TI  - [Malignant mesothelioma: incidence, survival and relative risks in selected
      municipalities 1943-1992].
AB  - The development in incidence rates and survival in Denmark, and the rate-ratio in
      selected municipalities that had industries utilizing asbestos was studied in
      1865 cases of malignant mesothelioma identified in the Danish Cancer Registry
      1943-1992. For men a steady increase in the incidence to 1.6 per 100,000
      personyears in 1992 was found, while the rate for women decreased to 0.28 per
      100,000 personyears. Age-specific incidence rates were highest for the older age
      groups. An unexplained difference in the distribution of pleural and peritoneal
      cancers was seen between men and women. The average survival was 6.9 months for
      men and 7.8 for women and had not changed during the period of observation. The
      average rate-ratio for the selected municipalities was 1.97 (95% confidence
      intervals: 1.73-2.24) for men and 1.35 (1.08-1.69) for women. Improvements in
      working conditions in terms of minimizing asbestos exposure were introduced in
      1980. Considering the latency period from exposure to diagnosis of 25-30 years,
      the impact of this measure on the rate of incidence cannot be expected before the
      year 2000.

PMID- 9265328
TI  - [Randomized clinical trials in the Ugeskrift for Laeger 1948-1995].
AB  - The Danish Medical Journal (Ugeskrift for Laeger) was handsearched for randomised
      and pseudorandomised clinical trials over the years 1948-1995. We found 665
      trials of which 539 (81%) were classified as randomised; the randomisation method
      was not stated for 422 of them (78%) and was insufficiently described in the
      majority of the rest. This problem became worse with time (p = 0.01). In contrast
      to the international literature where the increase was more gradual and occurred
      several years later, the number of randomised trials increased markedly around
      1973. This change is associated with the introduction of courses in clinical
      research methodology during the previous years. Since randomisation is the most
      important safeguard against bias, the method should be described in detail.

PMID- 9265329
TI  - [Compression of the urethra by an arthrotic cyst].
AB  - A case is presented of an osteoarthrotic cyst of the pubic symphysis with a
      diameter of 32 mm that caused urinating problems because of posterior dislocation
      and compression of the urethra. X-rays showed osteoarthrosis of the pubic
      symphysis, and the 56-year old woman had a history of separation of the pubic
      symphysis at the age of 28.

PMID- 9265331
TI  - [Only extremely tired?].

PMID- 9265330
TI  - [Chronic radiodermatitis--a historical and current diagnosis].
AB  - Chronic radiodermatitis was already diagnosed a few years after the discovery of
      X-rays. Despite the fact that protection should be known to be necessary to avoid
      radiodermatitis, cases of chronic radiodermatitis still occur. The present case
      report describes a nurse who endured years of direct hand exposure, leading to
      chronic radiodermatitis ten years after cessation of exposure.

PMID- 9265332
TI  - [Nutrition in hospitals].

PMID- 9265333
TI  - [Obstetrics and the null hypothesis].

PMID- 9265334
TI  - [Penicillin treatment of extranosocomial pneumonia at Danish departments of
      internal medicine].

PMID- 9265336
TI  - [Urolithiasis].

PMID- 9265337
TI  - [Extracorporeal shockwave lithotripsy today--an assessment of current status].
AB  - Extracorporeal shock wave lithotripsy (ESWL) is standard therapy for
      urolithiasis. With comparable technical principles, various lithotripters have
      been developed and are in routine use. Renal pelvic stones, calyceal stones,
      ureteral stones, and other special forms can be treated with varying results.
      Currently, the so-called clinically insignificant residual fragments and the
      recurrence of calculi are under discussion. Whereas the side effects of ESWL are
      well known, studies comparing ESWL with other endourological procedures are still
      lacking.

PMID- 9265335
TI  - [Enuresis].

PMID- 9265338
TI  - [Extracorporeal shockwave lithotripsy in childhood].
AB  - In general, the criteria for treatment of urolithiasis in children are the same
      as those for adults. Today, extracorporeal shock wave lithotripsy (ESWL) is the
      method of choice for treatment of most pediatric urinary stones. Stone-free rates
      between 57% and 97% at short-term follow-up and 57%-92% at long-term follow-up
      have proven the efficacy of ESWL treatment in children. So far, there is no
      evidence of negative side effects of ESWL treatment in children in the long-term,
      confirming the safety of ESWL treatment seen in the short-term results. In
      particular, neither induction of hypertension nor deterioration of renal function
      have been detected in children when limitation of shock wave energy and shock
      wave numbers have been carefully observed.

PMID- 9265339
TI  - [Ureteral calculi. In situ ESWL treatment with booster technique].
AB  - After treatment of more than 3000 kidney and ureteral stones with the Siemens
      Lithostar Multiline the results of the first 1400 ureteral stone treatments using
      the "Booster technique" and 3-month follow-up findings are reported. There was a
      disintegration rate of 98% directly after treatment; 1 week after "Booster
      technique" treatment 96% of the patients were free of stones and without any
      symptoms. The 3-month follow-up showed a stone-free rate of 97%. Only in 13% of
      the cases auxiliary procedures were necessary, 7% of them before extracorporeal
      shock wave lithotripsy (ESWL) and 6% after ESWL. 43% of the treatments were
      performed without any premedication, anaesthesia or sedoanalgesia. Our data even
      prove that in situ ESWL is a safe and effective method for the treatment of
      ureteral stones. In comparison to endoscopic procedures, it is superior in regard
      to invasivity, side effects, complications and necessity of analgesia, while
      being just as efficient. Therefore it is recommended as first choice method in
      the treatment of ureteral stones.

PMID- 9265340
TI  - [Complications with portable ESWL--a multicenter study].
AB  - An increasing number of urological departments are taking advantage of portable
      lithotripsy units if a system is not available in their clinic or purchase does
      not seem feasible; however, infrequent application of ESWL in such a setting
      should not increase the rate of complications. From 1993 to 1995, up to 54
      urological departments using mobile lithotripsy units collected data concerning
      all major complications. A total of 12,901 treatments were performed which led to
      85 major complications (0.66%). Of them 64 were intrarenal or perirenal
      hematomas. There was no fatal complication. In three patients nephrectomy had to
      be performed subsequently. The probability of complications can be calculated
      according to these data. Overall, less frequent application of ESWL does not
      yield higher complication rates than those at ESWL centers where larger numbers
      of treatments are performed.

PMID- 9265341
TI  - [ESWL centers and determination of urinary calculus etiology. Results of a survey
      of 150 ESWL centers].
AB  - Questionnaires were mailed anonymously to 150 German shock wave centers. Twenty
      questions addressed the following areas of interest: Facilities of the
      extracorporeal shock wave lithotripsy (ESWL) center (technical, personnel,
      laboratory, etc.) Cooperation at ESWL center with referring urologists Laboratory
      facilities versus actual metabolic work-up. The return rate was 114 of 150 (76%).
      Surprisingly, at 58% of the centers the average number of treatments is less than
      two per day. In 30% of the centers only chemical stone analysis is done! The
      final conclusion was that ESWL has largely replaced the causal metabolic work-up
      and subsequent metaphylaxis as a symptomatic measure against urolithiasis.

PMID- 9265342
TI  - [Significance of "clinically insignificant residual fragments" (CIRF) after
      ESWL].
AB  - Almost 75% of all urinary calculi can be treated by extracorporeal shock wave
      lithotripsy (ESWL). In contrast to endoscopic and open-surgical procedures the
      patients are not immediately free of stones. The residual fragments after ESWL
      are called clinically insignificant residual fragments (CIRF), if the fragments
      are less than 5 mm in size and if there is the possibility of a spontaneous
      passage. But CIRF can cause ureteral obstruction. In addition, CIRF play an
      important role for the risk of stone growth and stone recurrence. The
      metaanalysis shows that it is not advisable to classify the CIRF only by their
      size. The morphological conditions of the urinary tract also have to be
      evaluated. Therefore, stone patients with CIRF after ESWL require a close follow
      up and timely adjuvant therapy. All aspects mentioned lead to the conclusion to
      use the term "CIRF" with caution.

PMID- 9265343
TI  - [Recommendations for metaphylaxis of urinary calculi--summary for routine
      practice].

PMID- 9265344
TI  - [Shock waves in orthopedics].
AB  - Extracorporeal shock waves have revolutionized urological stone treatment.
      Nowadays shock waves are widely used in orthopedics, too. This article reviews
      the applications of extracorporeal shock waves on bone and adjacent soft tissue.
      The osteoneogenetic effect of extracorporeal shock waves has been proven and can
      be used to treat pseudarthrosis with a success rate of around 75%. Shock waves
      have a positive effect in tennis and golfer's elbow, calcaneal spur, and the
      complex called "periarthritis humero-scapularis." The mechanism for this is not
      yet known, and results from large prospective and randomized studies are still
      lacking. However, the treatment has been performed many thousands of times. In
      patients in whom conservative treatment has failed surgery used to be the only
      choice, but its success rate barely exceeds that of shock wave therapy and
      surgery can still be done if shock wave therapy fails. Extracorporeal shock waves
      will have an impact on orthopedics comparable to its effect in urology.
      Scientific evaluations, professional certifications, quality assurance and
      reimbursement issues present great challenges.

PMID- 9265345
TI  - [Therapy with mitomycin C, folic acid and 5-fluorouracil in treatment of
      metastatic, refractory urinary bladder carcinoma--phase II study].
AB  - We performed a phase II trial with second-line chemotherapy in patients with
      refractory, metastatic cancer of the bladder. Second-line therapy consists of 2.6
      cycles of mitomycin-C, 5-fluorouracil and folic acid. Two patients suffered from
      WHO grade III side effects (nephrotoxicity, leukocytopenia). We did not find any
      complete or partial remission. Four patients had a stable disease; 3.3 months
      after therapy, patients developed tumor progression with a median survival of 9
      months. Four patients reported an improvement in quality of life. Since all
      patients received supportive care, improvement in quality of life cannot be
      related to chemotherapy alone. In conclusion, second-line chemotherapy with
      mitomycin-C, 5-fluorouracil and folic acid has no effect on refractory,
      metastatic cancer of the bladder and is no alternative for cisplatin and
      methotrexate-based chemotherapy.

PMID- 9265346
TI  - [Nosocomial infections caused by multiresistant pathogens. Clinical management
      exemplified by multiresistant Staphylococcus aureus].
AB  - Nosocomial infections are a serious problem for every hospital for medical and
      economic reasons. During the last few years, multiresistant strains have been
      coming to the fore. At the end of the 1970s, the first outbreaks of nosocomial
      infections of oxacillin- and methicillin-resistant Staphylococcus aureus strains
      (MRSA) were reported. MRSA outbreaks require a high degree of organization of
      medical and hygiene procedures for therapy and prevention. Taking our own
      experiences into consideration, the essential measures for controlling such
      infections are discussed.

PMID- 9265347
TI  - [Improved discrimination between prostatic carcinoma and benign prostatic
      hyperplasia by determination of free prostate-specific antigen percentage].
AB  - We investigated whether the free-to-total prostate-specific antigen (PSA) ration
      (f-PSA/t-PSA ratio; i.e. percentage of free PSA) represents a better
      discriminator for the detection of cancer of the prostate (CaP). In a
      retrospective analysis, the percentage of free PSA was determined in the sera of
      35 patients with histologically proven benign prostatic hyperplasia (BPH) and 35
      patients with clinically localized CaP. Patients with urolithiasis (n = 33)
      served as a control group. Serum levels of free PSA and total PSA were determined
      employing a chemiluminescent enzyme immunoassay. Patients with CaP demonstrated a
      lower percentage of free PSA (median: 8.7) than patients with BPH (median: 20.0;
      P < 0.001). Determination of the percentage of free PSA enhances the
      differentiation between BPH and CaP and may reduce the number of unnecessary
      biopsies in patients with an elevated PSA. Confirmation of our preliminary
      results is required.

PMID- 9265348
TI  - [Organ preserving surgery of testicular epidermoid cyst in the newborn infant].
AB  - Epidermoid cysts are rare, benign tumors of the testis or, less frequently, the
      inguinal cord. Generally, they affect males between 10 and 39 years. In newborns
      they are rare. We report on a newborn with an epidermoid cyst of the right testis
      that had been diagnosed in utero and was removed with preservation of the
      testicle.

PMID- 9265349
TI  - [Accessory spleen of the spermatic cord].

PMID- 9265350
TI  - [Pupilography in early diagnosis of primary open-angle glaucoma].
AB  - The pupil reactions in young subjects with emmetropic and myopic refraction, in
      normal subjects aged over 40, and in patients with primary open-angle glaucoma
      (POAG) are analyzed in relation to the trophic changes in the iris and functional
      activity of the ciliary muscle. These processes course in parallel with each
      other, but in POAG the changes in the pupil reaction are preceded by dystrophy of
      the iris and ciliary body, which is due to a slower conduction of pulses via the
      conduction routes. This permits the use of pupilography for early diagnosis of
      POAG.

PMID- 9265351
TI  - [Criteria for assessing the efficacy of brachytherapy of uveal melanomas,
      complications of therapy and there prevention].
AB  - The authors assess the efficacy of brachytherapy of uveal melanomas in 954
      patients. Strontium ophthalmoapplicators were used in 652, rutenium ones in 302
      patients. As a rule, Sr applicators were sutured in patients with tumors up to
      3.5 mm thick and Ru ones in cases with tumors thicker than 3.5 mm. A special
      program was used for individual approach and improving the accuracy of planning.
      A total of 74.5% of patients have been followed up for at least 3 years, with
      check-ups every 3-6 months. The effect of brachytherapy was considered positive
      in cases with complete resorption or at least 50% decrease of the tumor and a
      stable clinical picture for 9-12 months. In 60% of patients the tumor regressed
      completely, in 16% partially, and in 24% there were signs of activation of
      melanoma growth one year after treatment. The frequency of radiation
      complications was as follows: retinopaty, 3.15%; neuroretinopathy, 1.1%;
      hemophthalmia, 0.9%; neovascular glaucoma, 1.1%; cataract, 0.63%. The incidence
      of radiation complications increases with increase of the applicator power and
      rigidity of exposure. Computer planning of brachytherapy with due consideration
      for the size of the tumor and the eye and localization of the neoplasm for each
      case will help decrease the incidence of complications.

PMID- 9265353
TI  - [Experience of clinical use infrasound pneumomassage in the treatment of
      progressive myopia in schoolchildren].
AB  - Infrasound pneumomassage at a frequency of 4 Hz, duty factor 0.5, and amplitude
      0.1 kg/cm, 10-min exposures for 10 days, stabilized the course of progressive
      myopia, as shown by examinations 3 years after treatment. The most expressed
      changes were observed in various portions of the vascular membrane.

PMID- 9265352
TI  - [New therapy with blood components in vascular diseases of fundus oculi].
AB  - The concentrations of the hemostatic system components (plasminogen, fibronectin,
      alpha 2-macroglobulin, alpha 1 proteinase inhibitor, and antithrombin III) were
      measured in activated and intact plasma. Activated autoplasma was used in the
      treatment of patients with central chorioretinal dystrophy. After therapy vision
      acuity increased in 74.3% (52 eyes) and did not change in 25.7% (18 eyes) of
      cases.

PMID- 9265354
TI  - [Ophthalmophysiological features of applying soft contact lenses to correct
      myopia in pilots].
AB  - The development of effective methods for preventing and correcting myopia in
      pilots is one of the most important problems of aeronautic ophthalmology. The
      majority of Russian and foreign aeronautic ophthalmologists agree that contact
      correction is the principal method for repair of occupational vision of myopic
      pilots. Experiments with soft contact lenses with 38 and 70% humor content were
      carried out. The methodology was based on comprehensive examinations of the
      vision status and status of the organ of vision under common conditions on the
      Earth and during simulation of unfavorable flight factors. The results indicate
      that contact lenses are a safe means for correcting myopia in pilots. This is
      confirmed by the absence of unfavorable changes in the main visual functions and
      in the status of the anterior segment of the eye, by a constant level of visual
      working capacity, and by the absence of negative subjective sensations.

PMID- 9265355
TI  - [Clinical and immunological features of peripheral uveitis in children and
      adolescents. Differentiated treatment strategy].
AB  - Sixty-eight children with peripheral uveitis (PU) were examined, which is 11.5%
      of the total number of children with endogenous uveitis. In addition to the
      classical signs of PU, children often develop papillitis, corneal precipitations,
      and diffuse cataracts which are formed early. Clinical and immunological
      correlations were revealed, indicating a relationship between the clinical
      features and the disease etiology and pathogenesis: herpetic forms of PU
      (infectious and infectious-allergic) with immunopathological reactions to the
      retinal S-antigen only during late stages when the process takes a chronic
      course. Differentiated treatment strategy of PU with due consideration for the
      detected features is proposed.

PMID- 9265357
TI  - [Effect of active medium on sclera creep].
AB  - Irreversible stretching (creep) of the eye sclera, regarded as the cause of high
      myopia, has been studied experimentally. Both dramatic acceleration and
      appreciable deceleration of the bovine sclera creep have been observed in the
      presence of some enzymes. Connective tissue creep caused by static and cyclic
      mechanical stress (gravitation, blood pressure, etc.) can be associated with many
      age-specific and pathological changes. The authors believe that detection of
      appropriate creep inhibitors will make it possible to replace surgery with
      preventive therapy in ophthalmology and cosmetology.

PMID- 9265356
TI  - [Effect of ACTH4-10 on the course of inflammatory and regeneration processes in
      the rabbit cornea].
AB  - The effect of synthetic peptide ACTH4-10 on the course of healing of an
      experimental wound of the rabbit cornea was studied. Daily subconjunctival
      injections of the drug in a dose of 10(-8) M for 25 days boosted the migration of
      leukocytes and macrophages and increased the interstitial and keratocyte
      proteolysis during the first 10 days of the experiment. Subsequent follow-up
      showed manifest proliferation of fibroblasts and formation of fibrosis. These
      data demonstrate expressed effect of synthetic ACTH4-10 on the course of the
      inflammatory and regeneratory processes in the cornea after partial keratectomy
      and prove the possibility of short-term local therapy with this peptide as an
      agent improving corneal wound healing during the initial phases.

PMID- 9265358
TI  - [Service (computer) program for selecting magnifying means].
AB  - A service program for selecting magnifying means has been developed and tried in
      59 patients (110 eyes) with senile maculodystrophy and cataracts. Attempts at
      choosing traditional magnifiers (magnifying glasses, hyperoculars, telescopic
      eyeglasses, and contact lens-eyeglasses system) were made with due consideration
      for the focus of lesions and the anatomooptic parameters of the eye (corneal
      refraction, size of the anteroposterior axis, and clinical refraction). The
      results indicate that the proposed program helped effectively choose traditional
      magnifiers for the majority (81.35%) of the above patient population.

PMID- 9265359
TI  - [Software for automated follow-up of chronic outpatients].
AB  - A service program for selecting magnifying means has been developed and tried in
      59 patients (110 eyes) with senile maculodystrophy and cataracts. Attempts at
      choosing traditional magnifiers (magnifying glasses, hyperoculars, telescopic
      eyeglasses, and contact lens-eyeglasses system) were made with due consideration
      for the focus of lesions and the anatomooptic parameters of the eye (corneal
      refraction, size of the anteroposterior axis, and clinical refraction). The
      results indicate that the proposed program helped effectively choose traditional
      magnifiers for the majority (81.35%) of the above patient population.

PMID- 9265360
TI  - [Peripapillary geographic choriopathy].
AB  - Examinations of 179 patients with peripapillary geographic choriopathy (PGC)
      revealed that peripapillary landscape-like foci often involving the macula and
      periphery of the fundus oculi are the pathognomonic symptom of PGC which permits
      the diagnosis of the condition without additional examinations in more than 90%
      of patients. The incidence and types of complications are assessed. The
      possibility of a unilateral disease is proven. Previous data on the
      nontuberculous origin of PGC have been confirmed.

PMID- 9265361
TI  - [Clinical aspects of traumatic uveitis and causes of enucleation].
AB  - The authors analyze 37 cases with grave traumatic uveitis eventuating in
      enucleation. Terms of enucleation after the injury, type of the injury, clinical
      picture of chronic uveitis, echographic and electrophysiological findings are
      presented. In ten patients signs of sensitization to ocular tissues were detected
      in various periods after the injury. Sensitization was detected by the leukocyte
      migration inhibition test (LMIT). The authors regard the results as a response to
      release of tissue antigens in the bloodflow because of impairment of the blood
      eye barrier caused by the trauma. The authors claim that the results of LMIT in
      traumatic uveitis may be regarded as an additional, together with the clinical
      symptoms, criterion among indications to enucleation.

PMID- 9265362
TI  - [Sympathetic ophthalmia 21 years after penetrating eye injury].
AB  - Sympathetic ophthalmia developed 21 years after penetrating wound during a
      relapse of posttraumatic uveitis 10 days after enucleation of the injured eye and
      discontinuation of dexamethasone. The diagnosis was confirmed histologically. The
      authors believe that enucleation and discontinuation of steroids provoked the
      development of inflammation in the paired eye.

PMID- 9265363
TI  - [Modern data on etiology and pathogenesis of posttraumatic proliferative
      vitreoretinopathy].

PMID- 9265364
TI  - [Methods for clinical studies of sclera in myopia].

PMID- 9265365
TI  - [Biomechanical characteristics of interactions between the drainage and
      accommodation regulatory systems of the eye in health and in contusion lens
      subluxation].
AB  - Biomechanical aspects of joint functioning of the accommodation system of the eye
      and the system regulating the discharge of intraocular fluid are considered
      proceeding from the concept of joint automated regulation. A multifunctional
      biomechanical model of the eye, created by the authors on the basis of numerous
      data and permitting them to quantitatively trace the relationships in the
      functions of the drainage and accommodation intraocular regulatory systems in
      health and in contusion subdislocation of the lens, is analyzed for various
      clinical situations. Theoretical and practical prerequisites for the development
      of novel methods for the diagnosis and treatment of primary open-angle and
      secondary phacotopic glaucoma are discussed, specifically, regulation of
      intraocular fluid discharge by purposeful shifting of the range of activity of
      the accommodation regulatory system. A detailed analysis of mutual functioning of
      the above ocular systems is practically important for clinical ophthalmology, for
      it accelerates the development of novel methods of diagnosis and pathogenetically
      based therapy of a number of ocular diseases.

PMID- 9265366
TI  - [Surgical treatment of eyeball atrophy with biological implant material
      alloplant: the structure and time course of morphological and physiological
      changes].
AB  - The time course of changes in the size of the eyeball and in intraocular pressure
      (IOP) is analyzed in 50 patients with posttraumatic subatrophy of the eyeball
      subjected to surgical treatment making use of the Alloplant biological materials
      and followed up for at least 3 years. The methods of dispersion, factor, cluster,
      and discriminant analysis have been used. The phases of the initial (directly
      after surgery) and remote changes were distinguished; changes in the size of the
      eyeball virtually did not depend on changes in IOP. Typological groups (clusters)
      of dynamic changes in the size of the eyeball and IOP were distinguished.

PMID- 9265367
TI  - [Determination of tetracycline in bones, mechanically separated bones and meat
      using HPLC and microbiological plating methods].
AB  - HPLC method with solid phase extraction, and microbiological agar diffusion tests
      for determination of oxytetracycline (OTC), tetracycline (TC) and
      chlortetracycline (CTC) in bones, mechanically separated beef and bones were
      developed. Both mechanically separated bones and bovine flat bones showed the
      highest yield of tetracyclines by HPLC method. Among tetracyclines, the highest
      yield was determined in chlortetracycline. The strains of Bacillus subtilis (PH
      6.0) and B. stearothermophilus showed the highest sensitivity to the presence of
      tetracyclines.

PMID- 9265368
TI  - [Survival of Salmonella typhimurium in the solid fraction from a farm waste water
      treatment plant].
AB  - Survival of Salmonella typhimurium pathogens was followed in the slurry solid
      fraction from a pig farm waste water treatment plant. The tested S. typhimurium
      pathogens have survived for 117 days. The solid fraction was kept in the
      laboratory at 20-23 degrees C. Indicatory microorganisms at the beginning of the
      experiment numbered 10(8)-10(9) CFU in 1 ml sample. This number decreased by 4-5
      series throughout the experiment, except for faecal coliform bacteria, which were
      not detected after 43 days of cultivation. Enterobacteria showed a decreasing
      tendency until day 83, however, on the final sampling (day 117) their count was
      almost double. Of physico-chemical parameters, pH showed the most striking
      variations. Its initial value of 6.9 increased to 8.1 at day 30, then decreased
      to 7.2 at day 43, and increased to 7.7 at the end of the experiment. Ammoniacal
      nitrogen in solid fraction was almost twice as high as the initial level. Other
      physico-chemical parameters were not changed significantly throughout the
      experiment. On the results of this experiment, decimal reduction times T90 were
      determined for indicatory microorganisms during the storage of solid fraction
      under constant conditions: psychrophilic bacteria 31.25; mesophilic bacteria
      38.12; coliform bacteria 27.49; faecal streptococci 24.57 and enterobacteria
      30.46 days. These data suggest a relatively long time of survival for indicatory
      microorganisms in the solid fraction from agricultural waste water treatment
      plants.

PMID- 9265369
TI  - [Bionomy, occurrence and importance of the giant liver fluke (Fascioloides
      magna), an important parasite of free-living ruminants].
AB  - The paper summarizes the most important knowledge of the giant liver fluke of
      ruminants, Fascioloides magna, with respect to its occurrence throughout the
      Northern Hemisphere, its fenotypic and genetic discriminative characteristics,
      its pathogenicity in various obligatory and facultative hosts and possible
      prophylaxis and medical control. The paper emphasizes the fact that new natural
      foci with heavy F. magna infections of deer regularly occur in Europe.

PMID- 9265370
TI  - [Dr. Edward Babak, professor of veterinary medicine].

PMID- 9265371
TI  - Frozen tail or limber tail in working dogs.

PMID- 9265372
TI  - [War injuries of the rectum and perineum].
AB  - The treatment results of 35 wounded with rectal and perineal lesion, treated in
      the period from 1991 to 1993 were analyzed retrospectively. In military
      hospitals, 82% of wounded were primarily surgically managed. The majority (65.8%)
      was with injury of intraperitoneal rectal segment, 10 patients (28.5%) were with
      the lesion of extraperitoneal segment and 2 patients (5.7%) were with the injury
      of anal tract and perineum. The injuries were mostly inflected by the bullets of
      various calibers (42.6%). Multiple or combined injuries were found in 91.6% of
      wounded with rectal injury and 38.2% of them were managed within 6 hours after
      injury. Different surgical procedures, most frequently the lesion suture and
      proximal colostomy (n = 14) were primarily used. Postoperative complications
      occurred in 10 wounded (28.6%). In 3 wounded it was reintervened by Hartmann's
      procedure. Mortality rate was 8.5% (n = 3). Anorectal war injuries are the most
      severe of all the colonic injuries. To our experience and the unique war surgical
      doctrine in the primary treatment of rectum injury, the most important is to
      perform terminal colostomy, injury suture (always intraperitoneal, and
      extraperitoneal if possible, including the sphincter muscles approximation) and
      presacral drainage.

PMID- 9265373
TI  - [Endobronchial metastases in extrapulmonary malignant tumors].
AB  - Endobronchial metastases of extrapulmonary malignant tumors are very rare and
      they appear in 1-2% of all the pulmonary metastases cases. By their endoscopic
      presentation, they are similar to primary bronchogenic carcinoma. Eleven patients
      with endobronchial metastases were presented, 8 male and 3 female. The average
      age was 58.27 years (from 37 to 72 years). Primary renal carcinoma existed in 2
      patients. The one was operated 5 years before the metastases appeared in
      bronchus, and the metastases in bronchial wall contributed to the discovery of
      primary tumor in the other patient. Endobronchial metastases appeared in 3
      patients, 2 years after the surgery of malignant colonic or rectal tumor, and in
      fourth patient it appeared 5 years after the surgery. One female patient
      sustained mastectomy and the radiation therapy was performed 11 years before the
      bronchial metastases occurred and the other female patient had the disease
      revealed a year ago and the polytherapy was performed. In the female patient with
      non Hodgkin Lymphoma, the change in bronchus was revealed simultaneously as the
      primary disease. Endobronchial metastases appeared in 2 patients two years after
      the surgery of malignant melanoma. The disease diagnosis was set by clinical
      radiological examination, by endoscopy and by the comparison of histopathologic
      finding of primary carcinoma and metastases.

PMID- 9265374
TI  - [Use of the Karnofsky index in the evaluation of patients with acute leukemia].
AB  - The longitudinal study of prospective character was performed during the
      treatment with the aim to test if Karnofsky's index is an instrument susceptible
      to the changes in performance status in the population of adult patients with
      acute leukemia. Performance status points out the person's independence in every
      day activities and personal care, and more widely, the independence in social and
      other activities. The aim was to establish its changes in adult patients and its
      possible prognostic value for the therapy success. The prognostic value of
      person's activity level was confirmed for the survival length and the lasting,
      but not for the complete remission achievement. It was concluded that Karnofsky's
      index was sensitive only for large changes in functional status of acute leukemia
      patients.

PMID- 9265375
TI  - [Clinical characteristics and perplexities in the treatment of chronic Lyme
      borreliosis].
AB  - The frequency of symptoms and signs in 52 patients with chronic Lyme borreliosis
      was analyzed in the study. The significantly higher frequency of: headache,
      myalgias, cranial neuritis, chronic dermatitis, ataxia and arrhythmia (p < 0.05)
      was found in the group of untreated (n = 31) in the early phase compared to the
      frequency of the same symptoms in the group that was treated (n = 21). The
      neuropathy of sensitive type was more frequently noticed in that group (p <
      0.01). The treatment of patients with Lyme borreliosis in the early stage should
      be started as soon as possible and should be performed until the probable
      elimination of significant decrease of causative agents number in the tissues.

PMID- 9265376
TI  - [The value of echotomographic measurement of gallbladder volume in the evaluation
      of its contractility].
AB  - Ultrasonographic examination of the gallbladder was performed in 2 patient
      groups: 20 volunteers (group I) and 20 patients with cholelithiasis (group II).
      Gallbladder volume was echotomographically measured before and after holagogue
      was administered. Dodd's ellipsoidal method was used for the elevation of
      gallbladder contractility. The mean value of gallbladder contractility was 69.9%
      in the group of volunteers. After the holagogue administration, the decrease of
      gallbladder volume was noticed in all the studied patients. In group of patients
      with cholelithiasis, the reaction after holagogue administration was different:
      the increase of gallbladder volume was noticed in 8 patients after the holagogue
      administration and the poor gallbladder contractility (below 50%) was noticed in
      8 patients. Four patients had no reaction after the holagogue administration.
      Echotomography was determined to be reliable method in the diagnosis of
      gallbladder contractility disturbances.

PMID- 9265377
TI  - [Levels of progesterone, estrogen, FSH and LH in galactorrhea of unknown
      etiology].
AB  - Considering the frequent occurrence of idiopathic galactorrhea in the women of
      fertile age, the hormone status was investigated in 50 patients aged from 20 to
      40 years. The FSH, LH, estradiol and progesterone hormones were tested. The
      hormone level was estimated from venous blood serum in the stage I of menstrual
      cycle (on 10th day) and in the stage II of cycle (on 22nd day). Patients were
      divided into 3 groups (related to menstrual cycle): with regular cycle, with
      irregular and with amenorrhea. Control group consisted of 21 healthy subjects.
      The changes in levels of FSH and LH were not found in the patients with
      galactorrheas of unknown etiology. Progesterone level was significantly lower (p
      < 0.05) in the patients with irregular cycle. Progesterone level was also
      significantly lower in the patients with amenorrhea and irregular cycle (0.01)
      and it was significantly raised in the patients with regular cycle (p < 0.05).
      Significantly higher estrogen (p < 0.05) was found in the patients with
      amenorrhea, and in the other groups there were no significant changes in estrogen
      level.

PMID- 9265378
TI  - [The role of nitric oxide in the pathogenesis and therapy of hemorrhagic shock].

PMID- 9265379
TI  - [Postoperative spinal peridural fibrosis].

PMID- 9265380
TI  - [Hematopoietic growth factors--physiology and therapeutic use].

PMID- 9265381
TI  - [Current knowledge of posttraumatic AV fistulae and pseudoaneurysms].

PMID- 9265382
TI  - [Therapy of nephrotic syndrome in membranous glomerulonephritis].

PMID- 9265384
TI  - [Heparin-induced thrombocytopenia].

PMID- 9265383
TI  - [Discrepancy of clinical neurologic findings and verified developmental
      malformation of the CNS].

PMID- 9265385
TI  - [Systemic inflammatory reactions to extracorporeal therapy measures (II):
      Cardiopulmonary bypass].
AB  - About 65,000 cardiac patients undergo surgery annually in Germany with the
      assistance of cardiopulmonary bypass. The "post pump inflammatory response" (the
      systemic and myocardial inflammatory response syndrome post cardiac surgery),
      triggered at least in part by the cardiopulmonary bypass, contributes
      substantially towards morbidity (e.g., myocardial depression) and mortality in
      these patients. The main mechanisms underlying this inflammatory response are the
      complement cascade, the activation of blood cells, the release of cytokines and
      the induction to nitric oxide synthesis. The relative importance of each
      individual factor, however, is still a matter of debate. Scoring systems and
      measurements of tumor necrosis factor-alpha, as well as soluble tumor necrosis
      factor receptors, allow the early detection of an "escalating inflammatory
      response" in 2-10% of all patients, which is associated with a worse prognosis.
      Therapeutic attempts to suppress these systemic and myocardial inflammatory
      reactions focus on blockade of the complement system, coating of CPB membranes
      with heparin, leucocyte depletion and attenuation of leucocyte function,
      elimination of toxins and mediators by means of hemofiltration, as well as on the
      administration of antiproteases, antioxidants, oxygen radical scavengers and also
      of immune globulins.

PMID- 9265386
TI  - [Rational cardiologic diagnosis after cerebral ischemic event].
AB  - Stroke continues to be a serious socioeconomic problem in the industrialized
      countries. The three disease processes responsible for most ischemic
      cerebrovascular events (CVE) are large-vessel and small-vessel atherothrombotic
      disease and, in up to 20-30% of cases, cardiac embolism. Data from the literature
      show that life expectancy after CVE is mainly dependent on the coexistence of
      cardiac disease. It is the responsibility of the cardiologist to exclude or
      identify the source of cardiac embolism and to initiate adequate treatment for
      the prevention of recurrences, as well as to diagnose, and treat any concomitant
      cardiac disease which may be present. We propose a cost-effective algorithmic
      approach to help the cardiologist in the diagnosis and treatment of patients with
      transient ischemic attacks and ischemic stroke.

PMID- 9265387
TI  - [Glycopeptide resistant enterococci. Occurrence, distribution, resistance
      transmission, significance].

PMID- 9265388
TI  - [Systemic inflammatory reactions to extracorporeal therapy measures (I):
      Hemodialysis and hemofiltration].
AB  - Hemodialysis and hemofiltration (intermittent or continuous) are the most
      frequently applied extracorporeal treatment strategies, enabling survival of
      patients with acute or chronic renal failure. To a various degree on the other
      hand they induce an undesirable inflammatory response summarized as
      bioincompatibility. Apart from the quality of the dialysate the composition of
      the dialytic membrane itself appears to be of very great importance in triggering
      this inflammatory process. The main humoral and cellular mechanisms underlying
      this inflammatory response are the activation of complement cascade, the
      activation of blood cells, the release of cytokines and the induction of nitric
      oxide synthesis. Various laboratory tests have confirmed a lower degree of
      inflammatory response on using synthetic membranes in comparison with cuprophane
      membranes. The importance of these differences in the treatment of dialysis
      patients with respecto to intradialytic complications and long-term morbidity and
      mortality, is, however, still a matter of debate. The results of clinical
      investigations to date are conflicting and have not yet clearly proven, whether
      implementation of synthetic membranes is of any benefit to dialysis patients or
      not. Apart from the cost factor there is no argument in favour of using
      cuprophane membranes.

PMID- 9265389
TI  - [Vancomycin resistant enterococci in Austria].
AB  - This study reports pheno- and genotypical analysis of 9 isolates of vancomycin
      resistant enterococci (VRE) and 5 vancomycin-sensitive enterococci (VSE) in
      Austria: 5 E, faecium isolates of 4 patients (the sole patients demonstrating VRE
      at the University Hospital of Innsbruck in 1994 and 1995), 3 glycopeptide
      sensitive isolates collected in Innsbruck in February 1996 for epidemiological
      analysis, and 6 enterococcus isolates from the University Hospitals of Vienna and
      Graz. The pheno- and genotypical analyses of all glycopeptide highly resistant E.
      faecium and E. faecalis isolates indicated the presence of VanA type resistance.
      One E. casseliflavus strain with intrinsic VanC-1 resistance showed a
      characteristic constitutive low-level resistance to vancomycin and susceptibility
      to teicoplanin. Genotyping with macro-restriction analysis demonstrated that 3
      VRE isolates of the 5 E. faecium specimens were identical; the same applied to 2
      VSE isolates. The two patients with VRE had been cared for at the same time in a
      surgical ICU and likewise, the two patients with VSE were simultaneously treated
      at a neurological ICU. The genotyping of E. faecalis strains showed that two
      strains of the three VRE isolates exhibited identical patterns. Epidemiological
      investigation did not reveal a mode of transmission for this cluster. Two of the
      8 patients with VRE died within 60 days after isolation of the bacteria; the
      doctors in charge did not consider that the enterococci had been the cause of
      death. The results of our study indicate that oral vancomycin administration to
      humans is a primary cause of VRE in Austrian hospitals. In Austria approximately
      66 kg vancomycin, 20% of it given orally, are administered to patients per year.
      Approx. 18-20 tons Avotan (active ingredient Avoparcin-10%)/year were used in
      Austria; as of April 1, 1997 the use of this animal foodstuff supplement is
      prohibited by the European Commission.

PMID- 9265390
TI  - [Reduced lung function parameters after physical exertion in Austrian Alps in
      ozone concentrations below the legal warning limit].
AB  - The ambient ozone concentration has increased greatly over the past decades,
      which may lead to environmental health problems, especially during the summer.
      WHO guidelines recommend an 8 hour mean value of < or = 60 ppb ozone without
      health risk. The aim of the present study was to investigate if elevated zone
      concentrations at moderate altitudes in the Austrian Alps, characteristic of the
      situation in the summer months, influence pulmonary function after physical
      exercise. 24 male non-smokers (mean age 26.7 +/- 4 years) were investigated in
      the Tyrol (Pitztal) at a mean sea level of 2434 m. During a mountain-guide course
      lasting for 6 days the subjects were physically active all day long. Spirometry
      was performed in the morning and in the evening after 8 h of exercise. Ozone and
      PM10 concentrations were measured on site. The ozone 24 hour mean values ranged
      between 53 and 71 ppb. A mean decrease of 5.3% (p < 0.00001) was measured in
      forced vital capacity (FVC) and forced expiratory volume (FEV1) at t3,m in
      immediately after the highest ozone 24 hour mean value had been registered (71
      ppb). A clinically relevant decrease of FVC and FEV1 > 10% was observed at t3,m
      in 35% of the subjects. However, a linear dependence of lung function changes on
      the ozone 8 hour mean values was demonstrable for all measuring points only in
      10% of these subjects. In 90% of the subjects with a decrease of lung function
      parameters > 10%, this reduction was at least not monocausally linked to ozone.

PMID- 9265391
TI  - [Contribution of spontaneous EEG to understanding cognitive functions].
AB  - Probability mapping of amplitude and coherence based on spectral analysis of the
      on-going EEG turned out to yield information on the cooperation of brain areas
      during cognitive processes. The method is based on comparing these two parameters
      during the performance of a mental task with the respective values of the EEG at
      rest before and after the task. For each of six frequency bands, spanning and
      entire EEG spectrum, the signs of significant changes of these parameters at the
      recording electrodes (19) and between all recording sites (19 x 18) are entered
      into schematic maps, representing the brain as seen from both sides and from the
      top. The results have proved to be largely task-specific for mental processes in
      both groups and individual studies. They are considered as electrical
      manifestations of differential attention. Since they may encompass EEG periods of
      even several minutes, these maps allow observations of average EEG
      characteristics even in complex, long-lasting mental accomplishments. The
      usefulness of the method is illustrated by four examples: doing mental
      arithmetic, listening to and composing music, simultaneous interpretation and
      contemplating and memorizing pictures.

PMID- 9265392
TI  - [Morphological changes in human colon carcinoma after chemotherapy with 5
      fluorouracil--a study in the nude mouse model].
AB  - Colorectal cancer represents one of the most important challenges in the field of
      cancer chemotherapy. 5-fluorouracil (5-FU) is used as the first-choice
      chemotherapeutic agent in the treatment of advanced gastrointestinal cancer.
      Despite this fact very little is known about the morphological changes of colon
      carcinoma after treatment with 5-FU. Thymusaplastic nude mice (n = 59) with
      subcutaneously heterotransplanted human coloncarcinoma (tubulo-papillary
      adenocarcinoma, grade II-III) were treated with 5-FU (40 mg/kg/body weight i. p.
      for five days). The animals were sacrificed, tumors were removed at 0 h, 24 h, 36
      h, 48 h, 54 h, 60 h, 66 h, 72 h, 94 h, 118 h, 240 h after chemotherapy and the
      tumor tissue was embedded for light-microscopic and ultrastructural examination.
      Hydropic mitochondria and cytoplasmatic vacuoles were observed in tumor cells as
      early as 0 h after chemotherapy. These changes displayed a focal pattern. Damaged
      tumor tissue was surrounded by tumor cells with intact ultrastructure. In some
      regions tumor cells were separated from the basal membrane and showed signs of
      necrosis. These focal changes within the tumor tissue were observed from 0-240 h
      after treatment. Tumor capillaries did not show any damage. Treatment with 5-FU
      led to focal cytotoxic effects in the tumor. The remaining intact vascular system
      of the tumor may be a target for new therapy modalities.

PMID- 9265393
TI  - [Liver transplantation and splenectomy in idiopathic portal hypertension].
AB  - Idiopathic portal hypertension (IPH) was diagnosed in a 30-year-old man. Clinical
      signs were splenomegaly, leucothrombocytopenia, and esophageal varices of fourth
      degree. The histology of the liver biopsy showed portal fibrosis with no evidence
      of cirrhosis. No causing agent or known disease could be found for the
      histopathological and clinical features. Due to a severe deterioration of general
      condition and a decline of synthetic liver function, liver transplantation and
      splenectomy were performed. The histological examination of the explanted liver
      revealed features of IPH, demonstrating portal fibrosis and dilated vessels
      adjacent to portal tracts; no cirrhosis was found. The postoperative recovery was
      without any severe complications. The duration of hospitalization was 28 days.
      Following liver transplantation, the esophageal varices disappeared and
      leucocytes, platelets as well as parameters of hepatic synthesis reached normal
      values. Initially, the immunosuppression was composed of prednisolon, tacrolimus,
      and antibodies against IL-2 receptors (BT 563) and was later continued with
      prednisolon and tacrolimus. Within the follow-up observation of 26 months, there
      was no evidence for graft rejection, severe infection, or occurrence of portal
      hypertension. Up till now the patient is in good condition with normal graft
      function. Liver transplantation may be a curative therapy for patients with
      advanced disease of IPH but the long-term follow-up after transplantation has to
      show whether IPH can reoccur.

PMID- 9265394
TI  - [Hepatitis B virus mutants--clinical significance].
AB  - Hepatitis B virus (HBV) mutants have recently been identified in patients with
      acute or fulminant as well as chronic infections. Naturally occurring mutations
      have been identified in all viral genes and regulatory elements, most notably in
      the genes coding for the structural envelope and nucleocapsid proteins. Mutations
      in the gene coding for the hepatitis B surface antigen (HBsAg) may result in
      infection or viral persistence despite the presence of antibodies against HBsAg
      (anti-HBs) ("vaccine escape" or "immune escape"). Mutations in the gene encoding
      the pre-core/ core protein (pre-core stop codon mutant) result in a loss of
      hepatitis B e antigen (HBeAg) and seroconversion to antibodies to HBeAg (anti
      HBe) with persistence of HBV replication (HBeAg minus mutant). Mutations in the
      core gene may lead among others to an "immune escape" due to a T cell receptor
      antagonism. Mutations in the gene coding for the polymerase/reverse transcriptase
      can be associated with viral persistence or resistance to nucleoside analogues.
      Thus, HBV mutations may affect the natural course of infection, viral clearance
      and response to antiviral therapy. Apart from the precore/core stop codon
      mutations, the exact contribution of specific mutations to diagnosis and therapy
      of HBV infection as well as patient management in clinical practice remain to be
      established.

PMID- 9265395
TI  - [Deletions of the short arm of chromosome 1 are an early event in development of
      colorectal carcinomas].

PMID- 9265396
TI  - [Preventive lamivudine against reinfection by hepatitis B after liver
      transplantation].

PMID- 9265397
TI  - [Hereditary pancreatitis is due to a mutation of the cationic trypsinogen gene].

PMID- 9265398
TI  - [8th Workshop on experimental and clinical liver transplantation and hepatology.
      Wilsede, 12-14 June 1997. Abstracts].

PMID- 9265400
TI  - Proceedings of the 4th International Symposium on Retrovirus in Multiple
      Sclerosis and Related Diseases. Copenhagen, Denmark, September 26, 1996.

PMID- 9265399
TI  - Meeting of the Working Group on Epidemiology and Prevention of the European
      Society of Cardiology. Pilsen, Czech Republic, May 22-25, 1996. Abstracts.

PMID- 9265401
TI  - [Prostatitis and bladder neck obstruction].

PMID- 9265402
TI  - [1910-1911, a crucial biennium in the history of the Asociacion Espanola de
      Urologia (I). How our association was born].
AB  - Although the background and major details concerning the events that in 1911
      culminated with the creation of the Spanish Association of Urology are well known
      as they have been published earlier in several papers, until now and as far as we
      know, no paper had presented the dates and particulars of the preparatory and
      constituent meetings of the Society, the first Regulations, and the semblance and
      biographies of the project's main inspirators and initiators. This article,
      prepared with abundant material from newspapers and literature of the period,
      extricated from the resources of the National Library and the archives of the
      Royal Academy of Medicine in Madrid, uncovers some unpublished data on the
      foundation and its advocates, and rediscovers other that although published in
      journals at the beginning of the century, remained forgotten or were unknown for
      most urologists. In this way, we complete the history of a part of our past,
      perhaps the most interesting one, and that of its main players.

PMID- 9265403
TI  - [1910-1911, a crucial biennium in the history of the Asociacion Espanola de
      Urologia (II). Its founding members, the I National Congress and the first Record
      of the Minutes].
AB  - In May 1911, four months after the founding of the Spanish Association of
      Urology, the new medical association already had 53 founding and numerary members
      and held with dignity its first National Congress in Madrid. The success of this
      first meeting and its sessions was described not only by all the specialized
      journals of the time but also by the non-medical press, the chronicles and gossip
      news of which we broadly review in this paper. The reading of the Book of
      Proceedings of the I Congress of the S.A.U., considered today a bibliographic
      rarity, allows us to discover a large part of the historical background of the
      foundation; to know the name of the pioneers and inspirators of the Society; and
      to glimpse the splendid future of an entity that in less than a year and through
      the vigour of its promoters, would reach enormous notoriety within the country's
      health-care environment.

PMID- 9265404
TI  - [Testicular changes produced by alcohol].
AB  - Acting as a direct toxic through different mechanisms, alcohol causes many
      hormonal changes which induce sexual function impairment and fertility problems.
      We have used 36 white Wistar Lewis rats, divided in three large groups: 10%
      alcoholic, 25% alcoholic and control group for 55 and 95 days. The parameters
      studied were the rat's ponderal evolution, testicular volume and weight, testes
      and body weights ratio, as well as testes density and seminiferous tubule area.
      We found a decreased ponderal gain in animals receiving high doses of alcohol.
      Decreased testicular volume and increased density in long-term alcohol regime. At
      high dose and medium-term increased testicular weights were seen as compared to
      total weight of the rat. The area of the seminiferous tubule is reduced in all
      alcoholic groups.

PMID- 9265405
TI  - [The early diagnosis of prostate cancer in a selected population. The usefulness
      of PSAD, PSAD ad. and age-adjusted PSA in patients with a PSA between 4-10
      ngr./ml].
AB  - RATIONALE: Exposition of our experience in the early diagnosis of prostate
      cancer, based on the initial selection of patients. METHODS: Evaluation of
      patients from within the area covered by our hospital and seen for signs and
      symptoms of prostatism. Those with suspicion rectal examination (RE) or PSA
      greater than 4 ng/ml were further evaluated with transrectal ultrasound and
      prostate biopsy. RESULTS: Based on the biopsies of 700 patients, prostate
      carcinoma was diagnosed in 294/700 (42%). 55.72% patients with suspicion RE, and
      47.5% with PSA > 4 had cancer. In patients with PSA > 4 and non-suspicion RE,
      cancer was detected in 16.44%. The percentage of neoplasia in patients with PSA 4
      10 ng/ml and non-suspicion RE was 10%. As a result of these findings, 88 radical
      prostatectomies were performed. PASD and PASD ad. showed significant differences
      between patients with and without cancer, whether with (+)RE (p = 0.0001) or (
      )RE (p < 0.0004), unlike PSA that showed no differences. The diagnostic value
      shown by PSAD ad. in ROC curves was similar to that of PSAD. Value of age
      adjusted PSA was not higher than PSAD. CONCLUSION: Performance of prostate biopsy
      with a suspicion RE is recommended. If RE shows no suspicion, biopsy should be
      performed when PSA is > 10 ng/ml, and with PSA 4-10 ng/ml a biopsy is advocated
      with PSAD > 0.15.

PMID- 9265406
TI  - [Incidental prostatic adenocarcinoma in the ere of the PSA].
AB  - Prostate adenocarcinoma is occasionally and incidentally found in the prostate
      gland after enucleation through adenomectomy or transurethral resection
      (incidentaloma). We contribute 17 cases (3.38%) of incidentaloma found among 503
      patients who underwent adenomectomy vs. TUR due to prostate obstructive
      irritative symptomatology of likely benign etiology. The diagnostic methods,
      pathological findings, treatment and evolution in our series versus other recent
      ones are explained.

PMID- 9265407
TI  - [The complications of retropubic radical prostatectomy].
AB  - Between January 1989 and October 1995, 104 prostatectomies were performed in
      patients with prostate carcinoma in our centre. Mean follow-up 22 months, range 3
      84 months. Overall frequency of complications was 33%. No fatal complications
      were reported. Complications in the early post-operative occurred in 17 patients
      (16%); late complications in 18 patients (17%), the most frequent one was
      stenosis of urethrovesical by-pass. No case of total incontinence has been
      recorded. The rate of stress incontinence at 3 months was 36% and 15% at 9
      months.

PMID- 9265408
TI  - [An analysis of the prognostic factors in renal-cell carcinoma].
AB  - OBJECTIVES: The study proposes the analysis of the influence of gross,
      microscopical and clinical pathoanatomical prognostic factors in the survival of
      patients with RCC through univariance and multivariance statistical analysis, and
      its global evaluation as a predictive model. PATIENTS AND METHOD: The study
      involved 218 RCC cases operated on over 20 years, with a mean follow-up of 60
      months. RESULTS AND CONCLUSIONS: All prognostic factors studied have a
      significant influence on the survival. When studied jointly, they include
      separately and in order of significance the metastatic involvement, mitotic
      index, cava vein involvement, nuclear grade and sarcomatoid histologic pattern.
      Also, we confirm that considered jointly they conform a valid predictive model.

PMID- 9265409
TI  - [Verrucous carcinoma of the penis. A report of 6 new cases and a review of the
      diagnostic and therapeutic aspects].
AB  - Verrucous carcinoma of the penis accounts for 5-17.8% of total carcinomas in the
      referred location that are diagnosed in our environment. Six cases of this rare
      neoplasia have been treated in our service and revised retrospectively. The
      epidemiological, clinical, diagnostic and therapeutic aspects of our series are
      analyzed and the issues around them discussed. Eventually, the benign biological
      behaviour of this tumour warranting conservative surgical treatment is ratified.
      In selected cases where the therapeutic modalities used do not yield material for
      histopathological analysis (laser, cryotherapy, etc.) prior obtention of a deep
      biopsy of the lesion to identify the likely presence of a well differentiated
      epidermoid carcinoma is imperative. Also, every effort should be made to monitor
      the cases of associated premalignant conditions.

PMID- 9265410
TI  - [Determining factors in the success of the treatment of ureteral lithiasis by
      ESWL].
AB  - Shock-wave extracorporeal lithotripsy (SWEL) is admittedly the choice method for
      most ureteral calculi (UC). Treatment of 1.674 UC was carried out with a
      Lithostar (Siemens). Endourologic support manoeuvres (ESM) were used in 11.7%
      patients. To determine their statistical influence on treatment's result
      variables such as site, size, calculus density, obstruction and functionality of
      the renal unit, as well as presence of ureteral malformation, were analyzed. With
      an average of 1.3 sessions (9100 waves) success rate was 91.8% cases. Only the
      variables of size, obstruction and function showed statistical significance, thus
      identifying through a multistep logistic regression test the subgroup of calculi
      less likely to succeed (calculi > 1 cm2, with severe uropathy and functional
      annulment or delay). Complication were rare (7.5%) and minimally relevant. We
      conclude than SWEL is the first choice treatment for UC regardless the location.
      Ureteroscopy (UR) should be considered as the first option particularly in distal
      (iliopelvic ureter), obstructive calculi and those of difficult radiological
      study.

PMID- 9265411
TI  - [Eosinophilic cystitis].
AB  - Eosinophilic cystitis (EC) is a clinical-pathological entity characterised by the
      transmural infiltration of the bladder. It shows as an irritative mictional
      syndrome, though the most common sign is haematuria. Endoscopically it appears as
      an intravesical mass and is usually mistaken for a transitional tumour of the
      bladder. There has been many etiologies involved but not one single factor has
      been identified as responsible for the condition. Medical approach is the most
      appropriate initial treatment, but since the condition is so often mistaken with
      vesical tumoration, the first therapeutical attitude in most cases is
      Transurethral Resection (TUR) which, though more aggressive, is therapeutic,
      haemostatic and provides material for the pathoanatomical diagnosis.

PMID- 9265412
TI  - [The clinical evaluation of kidney trauma: the practical indications for
      complementary examinations].
AB  - The aim of the present work is to try to know the clinical data that can provide
      directions on the attitude to take with patients who seek advise with a suspicion
      of renal traumatism, thus allowing to select those that may require complementary
      examination. This is a retrospective revision of 190 cases of renal trauma
      admitted in our hospital between 1971 and 1992. We rated 3 large syndrome groups
      based on the patient's major signs and symptoms. The first indication in 71
      patients was haemorrhagic syndrome (shock or anaemia); 100 patients had
      microscopic or gross haematuria non-associated to anaemia; and 6 patients showed
      painful signs and symptoms. Existence of renal injury should be suspected in
      patients that came to the hospital with a background of trauma, microscopic or
      gross haematuria, shock with or without haematuria or intraabdominal lesions; the
      performance of complementary examinations is necessary in patients with evidence
      of gross haematuria, microscopic haematuria associated to shock or suspected
      associated extra-renal intra-abdominal lesions, or shock whether or not
      associated to haematuria.

PMID- 9265413
TI  - [Renal adenocarcinoma in a girl 13 years old].
AB  - Case report of a renal adenocarcinoma in a 13 year-old girl found during the
      study of a painless, gross haematuria of several months evolution. Apart from a
      review of signs and symptoms, diagnosis, therapeutical approach and other issues
      related to this tumour, the authors insist on the significance gross haematuria
      has in children presenting symptoms that should alert the medical profession
      about a possible neoplasia of this features, in spite of its rare occurrence.

PMID- 9265414
TI  - [Subcutaneous metastasis as the first manifestation of kidney cancer
      dissemination].
AB  - Presentation of an uncommon form of distant primary dissemination of renal
      adenocarcinoma (RA) 5 years after radical surgery, the subcutaneous metastasis.
      The patient underwent surgical resection of metastasis, and later developed early
      pulmonary, mediastinal and new skin metastasis. A review is made of the
      incidence, therapeutical approach and prognostic value of skin metastasis due to
      RA.

PMID- 9265415
TI  - [Bladder metastasis of lung adenocarcinoma].
AB  - Secondary or metastatic vesical tumours are a very uncommon condition (less than
      1% of vesical tumours). Dissemination routes are usually through blood and lymph,
      and diagnosis occurs typically in advanced stages. This paper presents one case
      of metastatic vesical neoplasia that developed 5 years after diagnosis of the
      primary lung tumour.

PMID- 9265416
TI  - [Renal-cell carcinoma and polycystic disease in an adult].
AB  - Polycystic disease of the adult is the most common presentation of renal cystic
      disease and is transmitted by dominant autosomic heredity. Development of renal
      cell carcinoma has been reported within this cystic disease, but the frequency of
      such coincidence is not higher than in the remaining population. Most of these
      tumours are found incidentally and may involve a diagnostic problem due to the
      marked distortion of the kidney's architecture produced by the polycystic disease
      of the adult.

PMID- 9265417
TI  - [Retrovesical schwannosarcoma].
AB  - Contribution of one case of retrovesical schwannosarcoma in a 23-year-old female
      patient, with discussion of signs and symptoms, diagnosis and treatment.
      Retroperitoneal schwannosarcoma is an extremely uncommon tumour. Diagnosis is
      always histologic and immunohistochemical. This is an extraordinary aggressive
      tumour, with low response to chemo- and radiotherapy. Surgery is the only
      curative treatment, and presents a high index of recurrence. Prognosis is sombre.
      We support the most radical surgical approach possible as the only definite
      diagnostic possibility, since it provides the best survival indexes and in any
      case, improves symptomatology of tumours not completely resectable.

PMID- 9265418
TI  - [A fibroepithelial polyp of the ureter. A report of 2 new cases].
AB  - Primal neoplasias of the ureter are very rare and account for less than 1% of all
      genitourinary tumours. Only 20% of them are benign, and the fibroepithelial
      lineage is the more frequent. We contribute two cases of fibroepithelial polyps
      of the ureter; a brief comment on the etiology of these lesions, the routine
      diagnosis procedures and current therapeutical options is presented. Due to
      breakthroughs in radiologic and endoscopic techniques for the upper urinary
      tract, a more precise pre-operative diagnosis of these lesions has been achieved
      as well as a more conservative therapy which avoids incorrect and unnecessary
      nephroureterectomies, so frequent in past times, considering the benign nature of
      this unusual pathology.

PMID- 9265419
TI  - [Renal hematoma as a result of internal ureteral catheterization].
AB  - INTRODUCTION AND OBJECTIVE: Urinary catheterization by means of an internal
      ureteral catheter in an usual procedure that may present complications. In this
      article we presented a case of perforation and later renal subcapsular hematoma
      after the placement of a "double-J" catheter. CONCLUSIONS: This complication,
      although rare, should be kept in mind. The manner of avoiding it is to maintain
      the tightness of the guidewire while inserting the ureteral catheter. Usually,
      the consequences are not life-threatening and are solved with conservative
      treatment. The administration of LFRE should be delayed until the resolution of
      the hematoma.

PMID- 9265420
TI  - [The proximal migration of a double-J catheter. A review of the predisposing
      factors. Apropos a case].
AB  - Case report of a patient bearer of a double-J ureteral catheter due to ureteral
      lithiasis. After persistent renoureteral pain and fever, the proximal migration
      of the catheter is confirmed radiologically. The predisposing factors for this
      complication, described in the literature, are reviewed.

PMID- 9265422
TI  - Specific and novel aspects of histamine H1-receptor antagonists. Dedicated to
      Professor Daniele Bovet.

PMID- 9265421
TI  - [A giant bladder hernia. Apropos a case].
AB  - From a clinical point of view, vesical hernia is an uncommon condition.
      Occurrence is more frequent in male. In most cases diagnosis follows surgical
      repair of inguinal hernia, to which it may be associated (1-10% depending on the
      series). Unless complications arise, it evolves asymptomatically or reveals its
      presence by the distinctive two-stroke miction. Although infrequent, the most
      significant complications are incarcerations and strangulation with secondary
      necrosis of the vesical wall. Diagnosis is confirmed by radiological techniques:
      intravenous urography (IVU), retrograde cystography or computerised axial
      tomography (CAT). Treatment is always surgical. This paper presents one case of
      massive vesical hernia and a review of the relative literature.

PMID- 9265423
TI  - Direct isoform analysis of high-mannose-containing glycoproteins by on-line
      capillary electrophoresis electrospray mass spectrometry.

PMID- 9265424
TI  - Prevention of central venous catheter-related bloodstream infection by use of an
      antiseptic-impregnated catheter. A randomized, controlled trial.
AB  - BACKGROUND: Bloodstream infection related to short-term use of noncuffed central
      venous catheters is a common and serious problem. Technologic innovations to
      reduce the risk for these infections are needed. OBJECTIVE: To determine 1) the
      efficacy of a novel antiseptic catheter in preventing central venous catheter
      related infection, 2) patient tolerance of this catheter, and 3) the sources of
      bloodstream infection originating from noncuffed, multilumen central venous
      catheters. DESIGN: Randomized, controlled clinical trial. SETTING: Medical
      surgical intensive care unit of a 450-bed university hospital. PARTICIPANTS: 158
      adults scheduled to receive a central venous catheter; 403 catheters were
      studied. INTERVENTION: Participants received either a standard triple-lumen
      polyurethane catheter or a catheter that was indistinguishable from the standard
      catheter and was impregnated with chlorhexidine and silver sulfadiazine.
      MEASUREMENTS: Catheters were studied for colonization and catheter-related
      bloodstream infection at removal; local and systemic effects of catheters were
      assessed. The origin of each catheter-associated bloodstream infection was sought
      by culturing all potential sources (skin, catheter segments, hubs, and infusate)
      and confirmed by restriction-fragment DNA subtyping. RESULTS: Antiseptic
      catheters were less likely to be colonized at removal than control catheters
      (13.5 compared with 24.1 colonized catheters per 100 catheters; relative risk,
      0.56 [95% CI, 0.36 to 0.89]; P = 0.005) and were nearly fivefold less likely to
      produce bloodstream infection (1.0 compared with 4.7 infections per 100
      catheters; 1.6 compared with 7.6 infections per 1000 catheter-days; relative
      risk, 0.21 [CI, 0.03 to 0.95]; P = 0.03). In the control group, 8 catheter
      related bloodstream infections were caused by Staphylococcus aureus, gram
      negative bacilli, enterococci, or Candida species; no infections with these
      organisms occurred in the antiseptic catheter group (P = 0.003). No adverse
      effects from the antiseptic catheter were seen, and none of the 122 isolates
      obtained from infected catheters in either group showed in vitro resistance to
      chlorhexidine-silver sulfadiazine. Cost-benefit analysis indicated that the
      antiseptic catheter should prove cost-beneficial if an institution's rate of
      catheter-related bacteremia with noncuffed central venous catheters is at least 3
      infections per 1000 catheter-days). CONCLUSIONS: The chlorhexidine-silver
      sulfadiazine catheter is well tolerated, reduces the incidence of catheter
      related infection, extends the time that noncuffed central venous catheters can
      be safely left in place for the short term, and should allow cost savings.

PMID- 9265425
TI  - Central venous catheters coated with minocycline and rifampin for the prevention
      of catheter-related colonization and bloodstream infections. A randomized, double
      blind trial. The Texas Medical Center Catheter Study Group.
AB  - BACKGROUND: Central venous catheters are a principal source of nosocomial
      bloodstream infections, which are difficult to control. OBJECTIVE: To determine
      the efficacy of catheters coated with minocycline and rifampin in preventing
      catheter-related colonization and bloodstream infections. DESIGN: Multicenter,
      randomized clinical trial. SETTING: Five university-based medical centers.
      PATIENTS: 281 hospitalized patients who required 298 triple-lumen, polyurethane
      venous catheters. INTERVENTION: 147 catheters were pretreated with
      tridodecylmethyl-ammonium chloride and coated with minocycline and rifampin.
      Untreated, uncoated catheters (n = 151) were used as controls. MEASUREMENTS:
      Quantitative catheter cultures, blood cultures, and molecular typing of organisms
      to determine catheter-related colonization and bloodstream infections. RESULTS:
      The group with coated catheters and the group with uncoated catheters were
      similar with respect to age, sex, underlying diseases, degree of
      immunosuppression, therapeutic interventions, and risk factors for catheter
      infections. Colonization occurred in 36 (26%) uncoated catheters and 11 (8%)
      coated catheters (P < 0.001). Catheter-related bloodstream infection developed in
      7 patients (5%) with uncoated catheters and no patients with coated catheters (P
      < 0.01). Multivariate logistic regression analysis showed that coating catheters
      with minocycline and rifampin was an independent protective factor against
      catheter-related colonization (P < 0.05). No adverse effects related to the
      coated catheters or antimicrobial resistance were seen. An estimate showed that
      the use of coated catheters could save costs. CONCLUSIONS: Central venous
      catheters coated with minocycline and rifampin can significantly reduce the risk
      for catheter-related colonization and bloodstream infections. The use of these
      catheters may save costs.

PMID- 9265426
TI  - Catheter-related bacteremia and outcome of attempted catheter salvage in patients
      undergoing hemodialysis.
AB  - BACKGROUND: Dual-lumen cuffed catheters are used for vascular access in patients
      undergoing hemodialysis. The incidence and appropriate management of catheter
      related bacteremia are unknown. OBJECTIVE: To determine the incidence and outcome
      of catheter-related bacteremia and to assess the efficacy of catheter salvage.
      DESIGN: Prospective, observational study. SETTING: University hospital inpatient
      service and four affiliated outpatient dialysis units. PATIENTS: 102 patients
      with end-stage renal disease who underwent hemodialysis with dual-lumen cuffed
      catheters between 1 April 1995 and 1 January 1996. MEASUREMENTS: Number of days
      that the catheter remained in situ, treatment (catheter removal or attempted
      salvage with antibiotic therapy), and outcome of bacteremia. Microbiological
      cultures were done to identify catheter-related bacteremia. RESULTS: 102 patients
      had a total of 16,081 catheter-days. Forty-one patients (40%) developed 62
      episodes of bacteremia (3.9 episodes per 1000 catheter-days [95% CI, 3.0 to 4.9
      episodes per 1000 catheter-days]). Twenty-four catheters (39%) were removed
      immediately, and 38 (61%) were left in place during treatment. Only 12 (32%) of
      the 38 catheters were salvaged successfully. Salvage was less likely to succeed
      in patients with gram-positive bacteremia than in patients with gram-negative
      bacteremia, but this difference was not statistically significant (P = 0.14).
      Nine of the 41 patients (22%) who developed bacteremia had the following
      complications: osteomyelitis (6 patients), septic arthritis (1 patient),
      infective endocarditis (4 patients), and death (2 patients). All complications
      followed an episode of gram-positive bacteremia, and none was associated with
      attempted catheter salvage. CONCLUSIONS: Bacteremia frequently occurs in patients
      undergoing hemodialysis with dual-lumen catheters. Antibiotic therapy without
      catheter removal is unlikely to eradicate catheter-related bacteremia in these
      patients, but attempted salvage may not increase the risk for complications.

PMID- 9265427
TI  - Risk of initiating antiarrhythmic drug therapy for atrial fibrillation in
      patients admitted to a university hospital.
AB  - BACKGROUND: The risks of antiarrhythmic therapy are increasingly recognized, but
      the risks associated with the initiation of antiarrhythmic therapy in patients
      hospitalized for atrial fibrillation are poorly defined. OBJECTIVE: To determine
      the incidence, time course, and predictors of adverse cardiac events that require
      intervention during initiation of antiarrhythmic drug therapy for atrial
      fibrillation. DESIGN: Retrospective chart review. SETTING: University hospital.
      PARTICIPANTS: 417 consecutive patients who underwent a total of 597 drug trials
      during a total of 550 hospitalizations for atrial fibrillation. INTERVENTION:
      Initiation of therapy with antiarrhythmic drugs: procainamide (189 trials),
      quinidine (179 trials), disopyramide (20 trials), propafenone (110 trials),
      flecainide (2 trials), sotalol (72 trials), and amiodarone (25 trials).
      Electrical conversion was performed during 247 trials. MEASUREMENTS: Incidence of
      adverse events and daily hazard rate were measured. Logistic regression was done
      to identify risk factors. RESULTS: During the 597 drug trials, 80 (13.4%) cardiac
      adverse events occurred in 73 patients. The risk was greatest during the first 24
      hours of therapy. Bradyarrhythmias were the most common adverse event, occurring
      in 47 trials (7.9%); prolongation of the QT interval warranting discontinuation
      of drug therapy (9 trials; 1.5%) and ventricular arrhythmias (8 trials; 1.3%)
      were less frequent. In multivariate analysis, previous myocardial infarction was
      associated with increased risk (odds ratio, 1.90 [95% CI, 1.05 to 3.43]) and the
      association between older age and increased risk (odds ratio, 1.29 per decade
      [CI, 0.97 to 1.72]) was of borderline statistical significance. CONCLUSIONS: A
      significant risk for cardiac adverse events exists during initiation of
      antiarrhythmic therapy in patients hospitalized for atrial fibrillation.
      Observation with electrocardiographic monitoring seems advisable for 24 to 48
      hours during initiation of antiarrhythmic therapy, particularly for elderly
      patients and patients who have previously had myocardial infarction.

PMID- 9265428
TI  - Thrombopoietin levels in patients with cirrhosis before and after orthotopic
      liver transplantation.
AB  - BACKGROUND: Thrombocytopenia is a common manifestation of cirrhosis. OBJECTIVES:
      To determine plasma thrombopoietin levels in cirrhotic patients with
      thrombocytopenia, monitor those levels before and after orthotopic liver
      transplantation, and compare thrombopoietin messenger RNA (mRNA) levels in liver
      samples from cirrhotic patients and controls. DESIGN: A cross-sectional study of
      patients with cirrhosis, including a small subset of patients who had orthotopic
      liver transplantation. SETTING: University-affiliated hospital. PATIENTS: 44
      patients with cirrhosis, including 17 patients who had orthotopic liver
      transplantation. INTERVENTION: Orthotopic liver transplantation. MEASUREMENTS:
      Plasma thrombopoietin levels in all patients, platelet counts in all patients,
      and thrombopoietin mRNA levels in liver samples from nine patients with cirrhosis
      and eight controls. RESULTS: Thrombopoietin levels were undetectable in 39 of 44
      patients with cirrhosis. In 16 of 17 patients, the levels became detectable after
      liver transplantation. Thrombopoietin mRNA levels were decreased in liver samples
      from patients with cirrhosis compared with controls (P = 0.0103). CONCLUSIONS:
      The low thrombopoietin levels in cirrhotic patients with thrombocytopenia and the
      increased levels after orthotopic liver transplantation suggest that impaired
      production of thrombopoietin may contribute to thrombocytopenia associated with
      cirrhosis.

PMID- 9265429
TI  - Reduced plasma concentrations of antituberculosis drugs in patients with HIV
      infection.
AB  - BACKGROUND: Reports suggest that antituberculosis drugs are malabsorbed in
      patients with advanced HIV disease. OBJECTIVE: To evaluate the pharmacokinetics
      of antituberculosis agents in HIV-seropositive patients at different stages of
      disease. DESIGN: Parallel study. SETTING: Two hospital outpatient clinics.
      PARTICIPANTS: 12 healthy volunteers, 12 patients with asymptomatic HIV disease,
      12 patients with symptomatic HIV disease, and 12 patients with symptomatic HIV
      disease and diarrhea. MEASUREMENTS: Drug plasma concentrations were measured over
      24 hours on day 4 of concurrent therapy. INTERVENTION: Oral isoniazid (300 mg/d),
      rifampin (600 mg/d), pyrazinamide (1000 mg/d), and ethambutol (1000 mg/d).
      RESULTS: Reduced total drug exposure to rifampin and pyrazinamide was associated
      with D-xylose malabsorption in persons with HIV infection or AIDS. Peak drug
      exposure to isoniazid was lower in patients with diarrhea. CONCLUSIONS: Reduced
      total drug exposure may be related to malabsorption in persons with HIV infection
      or AIDS.

PMID- 9265431
TI  - Reducing the risk for catheter-related infections: a new strategy.

PMID- 9265430
TI  - The role of intravenous amiodarone in the management of cardiac arrhythmias.
AB  - PURPOSE: To review the electropharmacology, clinical applications, side effects,
      and hemodynamic profile of intravenous amiodarone. DATA SOURCES: The MEDLINE
      database was searched for English-language material, including reports of
      clinical trials and in vivo studies, review articles, and abstracts presented at
      national symposia, that was published between 1985 and 1996. Bibliographies of
      textbooks and articles were also examined. STUDY SELECTION: Studies that reported
      on the efficacy, toxicity, and hemodynamic profile of intravenous amiodarone and
      studies that examined the pharmacologic behavior of intravenous amiodarone in
      laboratory models were reviewed. DATA EXTRACTION: Study design and quality and
      relevant data on efficacy of suppression and treatment of arrhythmias with oral
      and intravenous amiodarone therapy, the reported mechanisms of antiarrhythmic
      effect, and hemodynamic changes seen with therapy were analyzed. DATA SYNTHESIS:
      Amiodarone is a unique antiarrhythmic agent that is now available in oral and
      intravenous forms in the United States. The use of intravenous amiodarone in the
      short-term treatment of life-threatening or hemodynamically unstable rhythm
      disturbances has generated much interest. Amiodarone has many
      electropharmacologic actions, some of which differ between the oral and
      intravenous forms. The wide clinical application of amiodarone includes treatment
      and prevention of supraventricular and ventricular arrhythmias and arrhythmias
      related to myocardial infarction. Intravenous amiodarone is effective for
      supraventricular and ventricular arrhythmias that are resistant to other
      antiarrhythmic agents. The effectiveness of intravenous amiodarone as short-term
      treatment also suggests that the drug has an important role in protocols of
      advanced cardiac life support. Intravenous amiodarone seems to have an overall
      favorable hemodynamic profile and does not produce many of the unwanted long-term
      side effects associated with oral therapy. CONCLUSION: Intravenous amiodarone
      shows much promise for the short-term treatment of unstable arrhythmias. Its
      favorable hemodynamic effects and minimal short-term side effects make it an
      attractive option in the management of cardiac arrhythmias.

PMID- 9265432
TI  - The Nazi doctors and Nuremberg: some moral lessons revisited.

PMID- 9265433
TI  - Guidelines for assessing and managing the perioperative risk from coronary artery
      disease associated with major noncardiac surgery. American College of Physicians.

PMID- 9265434
TI  - Perioperative assessment and management of risk from coronary artery disease.
AB  - PURPOSE: To summarize available evidence on preoperative cardiac risk
      stratification so that the internist may 1) use clinical and electrocardiographic
      findings to stratify a patient's perioperative risk for myocardial infarction and
      death; 2) decide which tests provide useful additional risk-related information;
      and 3) understand the benefits, risks, and evidence surrounding the decision to
      undertake coronary revascularization before elective noncardiac surgery. DATA
      SOURCES: A MEDLINE search and review of the reference lists of identified
      articles. Sensitivities, specificities, and likelihood ratios for diagnostic
      tests were calculated, and a quality rating for study methods was applied. DATA
      EXTRACTION: Myocardial infarction and mortality were the major outcomes
      considered, and a quality rating for study methods was applied. DATA SYNTHESIS:
      Clinical and electrocardiographic findings, organized by multivariate prediction
      indices, accurately identify patients as having low, intermediate, or high risk
      for myocardial infarction or death. Pharmacologic stress imaging with thallium or
      echocardiography probably improves risk stratification for intermediate-risk
      patients having vascular surgery. These tests have not been shown to be effective
      prognostic indicators for patients having nonvascular surgery. No studies of
      angiography for risk prediction have been reported. Decision analyses and
      retrospective series suggest that the risks incurred by doing coronary
      angiography and revascularization before elective surgery outweigh the benefits.
      Prospective, controlled studies of coronary revascularization are lacking.
      Evidence from a randomized, controlled trial has shown a survival benefit with
      the perioperative use of beta-blockers in patients at risk for coronary artery
      disease. CONCLUSIONS: Evaluation of all surgical patients by use of clinical
      indices is recommended. Low-risk patients need no further evaluation before
      surgery. High-risk patients need optimal management of their high-risk problems,
      including (if appropriate) beta-blocker use, and may need to have their elective
      procedures canceled. Intermediate-risk patients probably benefit from further
      noninvasive stress testing, especially if they are having vascular surgery.
      Further clinical trials are needed for most areas of concern.

PMID- 9265435
TI  - Caring for strangers.

PMID- 9265436
TI  - Warfarin: less may be better.

PMID- 9265437
TI  - Warfarin: less may be better.

PMID- 9265438
TI  - Warfarin: less may be better.

PMID- 9265439
TI  - Warfarin: less may be better.

PMID- 9265440
TI  - Tuberculin skin testing.

PMID- 9265441
TI  - Tuberculin skin testing.

PMID- 9265442
TI  - Adolescent Nutritional Disorders: Prevention and Treatment. Proceedings of a
      conference. New York, New York, December 3-5, 1995.

PMID- 9265443
TI  - Imaging Brain Structure and Function: Emerging Technologies in the Neurosciences.
      Proceedings of a conference. Bethesda, Maryland, March 28-29, 1996.

PMID- 9265444
TI  - "Dr. Taglicozzi, I presume?".

PMID- 9265445
TI  - [Claude Nicolas Le Cat: on the opinion regarding stone adhesion to the bladder].

PMID- 9265446
TI  - [Orthotopic bladder substitution: II. Types and complications].
AB  - OBJECTIVE: In the last two decades, attention has been focused on the design of
      continent urinary diversion and orthotopic neobladder in an attempt to find the
      ideal bladder substitute. The more commonly utilized techniques of orthotopic
      bladder replacement are described and the urodynamic aspects and complications
      are analyzed. METHODS: The series of Studer, Hautmann, Kock, Pagano, Thuroff
      (Mainz Pouch) and Goldwasser and the relevant literature on this subject were
      reviewed. RESULTS/CONCLUSION: To date, similar functional results have been
      achieved by the different techniques of bladder substitution, although different
      intestinal segments are utilized. A longer follow-up is warranted to determine
      which is the ideal technique of bladder substitution.

PMID- 9265447
TI  - [Orthotopic bladder replacement: II. Functional results and complications in
      patients with Studer-type ileal neobladder].
AB  - OBJECTIVE: Since 1988, 100 Studer ileal low pressure urinary reservoirs have been
      performed at our institution. The functional results and the complications
      observed in these patients are presented. METHODS: Patients submitted to radical
      cystectomy and lower urinary tract reconstruction with the Studer technique from
      1988 to 1994 were retrospectively studied. All patients were males, their mean
      age was 60 years (37-75) and the mean follow-up was 18 months (6-72). The
      isoperistaltic ileal segment as antireflux mechanism was utilized in 97 cases and
      intussusception of the ileal segment to which the ureters were anastomosed in 3
      cases. Reinsertion of the ureter was done using the Wallace technique in 90 cases
      and by direct fixation according to a personal technique (H.V.) in 10 cases.
      Anastomosis of the neobladder and the urethra was done with the end of the second
      suture of the orthotopic reservoir. The neurovascular bands were preserved in 21
      patients less than 60 years old with tumor stage T2-T3a, according to the
      technique described by Walsh and Mostwin (1984). RESULTS: One patient died early
      postoperatively from sepsis. The early complications included urinoma (4%),
      urinary fistula (3%), intestinal fistula (2%), pulmonary complications (4%),
      pelvic hematoma (1%) and intestinal obstruction (3%). Only 4 of these patients
      required surgical resolution of the complication. The late complications included
      stricture of neobladder-urethra anastomosis (6%), lithiasis in neobladder (4%),
      ureteroileal stricture (8%), 5 renal units were lost, chronic urinary retention
      (5%), symptomatic metabolic acidosis (1%) and urinary infection (14%). Thirteen
      of these patients with late complications required surgery. At 6 months' minimum
      follow-up, 90% of the patients were continent during the day and 60% during the
      night. Overall, 36% of the patients recovered erection postoperatively; 76% of
      the patients with preserved neurovascular bands recovered erection. Forty-four
      percent of the patients claimed they had a satisfactory sexual activity
      postoperatively. CONCLUSION: The Studer neobladder permits voiding through the
      urethra, preservation of the upper urinary tract, the urinary infection rate is
      acceptable, the complication rate is low and it offers patients continence rates
      that allow them to have a good quality of life.

PMID- 9265448
TI  - [Epidermoid carcinoma of the penis. Review of 30 cases].
AB  - OBJECTIVE: To review our series of epidermoid carcinoma of the penis. METHODS: 30
      cases of epidermoid carcinoma of the penis are reviewed. The clinical features,
      tumor stage, grade, treatment and outcome are analyzed. RESULTS: The time to
      diagnosis ranged from one month to 10 years, mean 10.3 months (1 to 36);
      therefore the mean diameter of the tumors was significantly greater (1.9 cm) at
      the time of diagnosis than at the beginning of the lesion. Eighteen patients had
      tumor superinfection. Twenty-four patients (80%) had low grade carcinoma; 6 had
      verrucous carcinoma, 6 (16.7%) intermediate and one (3.3%) high grade. Total
      penectomy with perineal meatus was performed in 5 cases, 23 had a partial
      penectomy with 2 cm margin and circumcision was done in two cases. Patients with
      positive lymph nodes at exploration after antibiotic treatment (13 cases) were
      submitted to lymphadenectomy, which was associated with chemotherapy in 4
      patients. The surgical complications were mainly lymphorrhea and edema and
      infection of the surgical incision after lymphadenectomy. Complications at the
      site of penile resection were unusual. Only 6 patients have more than 5 years'
      follow-up (7-14), with only 1 local recurrence. The remaining patients have a
      mean follow-up of 22 +/- 16 months (6-60). Of these, only one patient had died
      from penile cancer (previously pT2pN0M0). This patient had lymph node and distant
      metastases 6 months following penectomy due to invasive local recurrence
      (pT3pN2pM1). Lymph node recurrence has been detected in three other patients.
      CONCLUSION: Inguinal lymphadenectomy is clearly of therapeutic value in cancer of
      the penis and performing it early in infiltrating tumors is likely to improve the
      outcome in these patients.

PMID- 9265449
TI  - [Bladder cancer survival, study of 557 cases identified at the autonomous
      community of La Rioja from 1975 to 1991].
AB  - OBJECTIVE: To analyze survival in 557 cases of bladder cancer that had been
      detected in La Rioja (Spain) from 1975 to 1991. METHODS/RESULTS: The Kaplan Meier
      and Mantel and Haenszel methods were used for the statistical analyses. The
      survival rate for each 5-year period analyzed was 69%, 58% and 73%, respectively.
      Most deaths occurred within the first 24 months. The survival rates were 25%, 21%
      and 0%, respectively, for infiltrating tumors and 84%, 76% and 85% for
      superficial tumors was of the. The survival rates for males and females were not
      statistically significant. CONCLUSION: The survival rate in patients with bladder
      cancer has increased. Patients with infiltrating bladder tumors have a worse
      prognosis. The survival rates for males and females are not statistically
      significantly different.

PMID- 9265450
TI  - [Neoplasm prevalence in renal transplantation].
AB  - OBJECTIVE: To analyze the prevalence of neoplasms in renal transplant patients
      and the relative risk for each tumor type according to the immunosuppression
      regimen. METHODS: 609 renal transplants were reviewed. The risk index was
      determined by the ratio of the cases observed and predicted. RESULTS: Tumor
      prevalence was 4.9% (30/609); 6.3% (25/393) were males and 2.3% (5/216) were
      females. The most common tumors were cutaneous tumors other than melanoma,
      accounting for 2.4% (15/609), followed by Kaposi's sarcoma, pulmonary epidermoid
      carcinoma and genitourinary tumors (0.5%) and non-Hodgkin lymphoma (0.3%). Tumor
      prevalence was 6.8% for the group treated with azathioprine-prednisone and 3.9%
      for the cyclosporine A-prednisone-treated group. The estimated relative risk of
      having a neoplasm was 10-fold higher for the males and 4.2-fold higher for the
      females vs the general population. The mortality rate was 36.6%; specifically
      tumor-related in 82%. The mortality rate for those with solid tumors was 77.7%.
      The long-term survival rate for the group that developed a tumor was
      significantly lower than that of the general population, 75% vs 53%, respectively
      (p < 0.05). CONCLUSION: In this series no significant differences were observed
      relative to tumor prevalence or type according to the immunosuppression regimen.
      A recipient of a renal graft has a higher risk of developing a tumor. Cutaneous
      tumors were the most frequent. The long-term survival is lower for recipients of
      renal grafts who develop a tumor.

PMID- 9265451
TI  - [Vascular prosthesis in kidney transplantation].
AB  - OBJECTIVE: Three cases of kidney transplantation that required a vascular
      prosthesis are described and the literature reviewed. METHODS: Of 920 cases of
      kidney transplantation, 3 required a vascular prosthesis to repair the aortoiliac
      vessels. One patient with severe atherosclerotic disease had an aorto-bifemoral
      prosthesis (Gore-Tex) six months before renal transplantation and the other two
      patients required a vascular prosthesis to repair iliac artery lesions discovered
      during transplantation. RESULTS: The initial surgical results were satisfactory.
      No complications arising from the vascular prosthesis were observed. Two patients
      have a functioning renal graft, but the third patient developed acute tubular
      necrosis and tubulo-interstitial rejection and died from acute pulmonary edema.
      CONCLUSION: The importance of the preoperative cardiovascular evaluation in
      patients undergoing kidney transplantation is underscored. Some patients may
      require a vascular prosthesis. We should therefore be familiar with the
      prosthetic materials and the surgical techniques, which are not particularly
      difficult, and optimum results can be achieved. In patients with both end-stage
      renal disease and severe aortoiliac atherosclerotic disease, the controversy
      remains whether aortoiliac repair and kidney transplantation should be done
      simultaneously or in two stages.

PMID- 9265453
TI  - [Paratesticular adenomatoid tumor].
AB  - OBJECTIVE: To report a case of paratesticular tumor involving the right testis.
      METHODS/RESULTS: A middle-aged male with a small paratesticular tumor involving
      the right testis is described. Treatment was by transscrotal surgical excision.
      The histological analysis of the surgical specimen disclosed a mesothelial tumor
      and no evidence of malignancy. CONCLUSION: Although the preoperative diagnosis of
      adenomatoid tumor is relatively simple when the epididymis is involved,
      localization in the testis is relatively difficult to determine. Surgical
      exploration of all intrascrotal and intratesticular tumors are advocated due to
      the risk of malignancy.

PMID- 9265452
TI  - [Yield of ultrasound-guided transrectal biopsy in the diagnosis of prostatic
      cancer in symptomatic patients].
AB  - OBJECTIVE: The aim of this retrospective study was to evaluate the utility of US
      guided transrectal biopsy of the prostate in the diagnosis of prostatic cancer in
      symptomatic patients and its correlation with the digital rectal examination
      (DRE), PSA levels and ultrasound findings. METHODS: From 1994 to 1995, 427
      patients with prostatic symptomatology underwent prostatic biopsy. The mean age
      was 69.1 +/- 8.3 years (range 44 - 89). The criteria for biopsy were abnormal
      DRE, PSA > 10 ng/ml, abnormal US findings and/or PSA density > 0.15. RESULTS:
      Prostate cancer was confirmed in 42% of the patients. The incidence of cancer
      when DRE was abnormal was 73%, 46% when PSA was > 10 ng/ml and 55% when the US
      findings were abnormal; 82% for abnormal DRE and PSA > 10 ng/ml, and 84% when the
      criterion of abnormal US was included. The incidence of cancer when DRE was
      normal was 16%, 18% when combined with PSA > 10 ng/ml and remained unchanged when
      combined with the US findings. In patients with normal DRE and PSA between 10 -
      30 ng/ml, the incidence of cancer was 14% and 41% for those with PSA > 30 ng/ml.
      CONCLUSION: DRE was the best independent predictor of prostate cancer and the
      combination of abnormal DRE, PSA > 10 ng/ml and abnormal US findings gave the
      highest detection rate. The incidence of prostate cancer was very low in patients
      with normal DRE and PSA between 10 - 30 ng/ml, which may be due to the fact that
      the PSA levels are raised by the non neoplastic changes in the transitional zone
      in symptomatic patients.

PMID- 9265454
TI  - [Fournier's gangrene: computerized tomography findings].
AB  - OBJECTIVE: To describe a case of Fournier's gangrene. The CT findings confirmed
      the diagnosis and showed the extent of the lesion. METHODS/RESULTS: A young, male
      alcoholic developed Fournier's gangrene after an episode of urinary tract
      infection. The extent of the lesion observed on CT correlated with the surgical
      findings. CONCLUSION: CT evaluation of patients with Fournier's gangrene is
      advocated. In the case described herein, the extent of the lesion observed on CT
      correlated with the surgical findings.

PMID- 9265455
TI  - [Ureteral replacement with appendix].
AB  - OBJECTIVE: The scant references in the literature on the use of the appendix in
      ureteral substitution prompted us to describe the present case in whom this
      technique was utilized. METHODS: The surgical technique of appendiceal
      interposition to repair a defect approximately 10 cm long in the right ureter is
      described. Following excision of a mass arising from the adnexa that entrapped
      the ureter at the level of the pelvis, the defect was repaired with the appendix.
      RESULTS: At two years follow-up, the patient is well and right excretory system
      function is normal. CONCLUSION: Ureteral repair with the appendix is simple and
      easy to perform. However, the indications for appendiceal interposition are more
      limited than those of the classical surgical techniques.

PMID- 9265456
TI  - [Idiopathic retroperitoneal fibrosis simulating pelvic tumor with distal ureter
      infiltration. Report of a case].
AB  - OBJECTIVE: To describe a case of idiopathic retroperitoneal fibrosis with an
      unusual form of presentation. Similar cases reported in the literature are
      briefly reviewed. METHODS/RESULTS: Herein we describe a 50-year-old female
      patient with idiopathic retroperitoneal fibrosis presenting as a single,
      unilateral, pelvic focus that enveloped and infiltrated the distal ureter.
      Treatment and outcome are described and the possible options in similar cases are
      discussed. CONCLUSION: After discarding the more common causes of extrinsic or
      intrinsic ureteral obstruction, retroperitoneal fibrosis should be considered
      since it can mimic other conditions, as in the case described.

PMID- 9265457
TI  - [Usefulness of prostaglandin E1 in the diagnosis of corpora cavernosa fracture.
      Report of a case].
AB  - OBJECTIVE: To describe a case of rupture of the corpora cavernosa demonstrated by
      intracavernosal PGE1. METHODS/RESULTS: Herein we describe a patient with fracture
      of the penis in whom the degree of injury could not be determined by questioning
      and clinical inspection. The artificial erection test with intracavernosal PGE1
      was utilized to evaluate the ruptured corpora cavernosa. CONCLUSION:
      Intracavernous PGE1 is useful in the diagnosis of rupture of the corpora
      cavernosa and has minimum side effects.

PMID- 9265458
TI  - [Sertoli cell tumor. Report of a case].

PMID- 9265459
TI  - As originally published in 1989: Left coronary ostial stenosis: comparison with
      left main coronary artery stenosis. Updated in 1997.

PMID- 9265460
TI  - [Immobilized proteases and their activators as immunocorrective agents].
AB  - The influence of immobilized proteases such as catalytin (a complex preparation
      containing the protease terrilytin and the antiseptic catapol) and streptodecase
      (an activator of fibrinolysis proteases) on the humoral immune response induced
      by the thymus-dependent antigen (SRBC) under conditions of burns and
      Staphylococcus infected burns was studied. The immobilized proteases catalytin
      and streptodecase had an immunostimulating effect under conditions of extended
      burns. Catalytin had an immunocorrigating effect under conditions of the infected
      burns. It was suggested that the complex enzyme-containing preparation catalytin
      and the immobilized activator of fibrinolysis proteases streptodecase were
      promising immunopharmacological agents in combined treatment of pathological
      processes accompanied by the development of immune deficiency as a secondary
      condition.

PMID- 9265462
TI  - [Normalization of intestinal microflora and the general condition of mice of the
      JCR line as affected by Bifidobacterium concentrate].
AB  - It was shown experimentally that the use of liquid Bifidobacterium concentrate
      (B. bifidum 791 and B. adolescentis MS-42) led to normalization of microflora in
      mice which resulted in the improvement of the animal general state: increase of
      body weight, lower death rate, decreased late embryonic mortality, better hair
      growth.

PMID- 9265461
TI  - [Antioxidants and immunomodulating action of antibiotics and antibiotic-treated
      erythrocytes in staphylococcal infections].
AB  - Staphylococcus infection inhibited the T-dependent immune response, increased the
      serum levels of the lipid peroxidation products (LPP) i.e. fatty acid diene
      conjugates and malonic aldehyde and lowered the activity of the antioxidant
      system enzymes (ASE) i.e. superoxide dismutase and glutathione reductase in
      erythrocytes. After administration of amikacin or cephalexin the
      immunosuppressive effect induced by the staphylococci increased while the LPP
      content and the ASE activity in the infected host did not change. After injection
      of erythrocytes extracorporeally treated with the antibiotics the immune response
      increased, the LPP content decreased and the ASE activity increased. The free
      antibiotics increased the excretion of suppressing cytokines by glass adherent
      spleen cells. The antibiotic-treated erythrocytes induced the excretion of low
      molecular weight helper cytokines and high molecular weight antioxidant factors
      by the adherent spleen cells.

PMID- 9265463
TI  - [Listeriosis].

PMID- 9265464
TI  - [Effect of cyclosporin A and amphotericin B on protoplasts of Tolypocladium
      inflatum].
AB  - When added to the suspension of washed cells of Tolypocladium inflatum
      (cyclosporine-producing organism) in a concentration up to 100 micrograms/ml,
      cyclosporine A had no effect on permeability of the cell covers as judged by the
      quantity of the metabolites with the absorption maxima at 260 nm that leaked to
      the medium. When cyclosporine was added to the suspension of the T-inflatum cell
      protoplasts there was a significant increase in the metabolites leaking.
      Impairment of the permeability of the protoplast membranes was more marked in low
      potent strains. Impairment of the protoplast membrane permeability by
      amphotericin B was equal in both the high and the low potent strains and in this
      respect it was more active than cyclosporine.

PMID- 9265465
TI  - [Biosynthesis of avermectins: physiological and technological aspects].

PMID- 9265466
TI  - [Nisin: conditions for production and isolation of the drug].

PMID- 9265467
TI  - [Naphthoquinones as immunomodulators during intensive exertion].
AB  - Naphthoquinones such as phylloquinone, menadione and vicasol normalized or
      increased the immune response in rats after intensive physical load. The most
      marked immunomodulating effect was induced by phylloquinone. The naphthoquinones
      induced the development of immunostimulating properties in heavy red blood cells
      by the direct action on the cell membranes or indirectly through proteolytic
      enzymes secreted by hepatocytes. The proteolytic enzymes secreted to the vascular
      channel in physical load increased the susceptibility of heavy red blood cells to
      phylloquinone. Glycosaminoglycans accumulating in the vascular channel in
      physical load increased the resistance of heavy red blood cells to phylloquinone.
      Heavy red blood cells of physically loaded animals treated in succession with
      hyaluronidase and phylloquinone and red blood cells of intact rats after the
      incubation in the presence of trypsin and phylloquinone proved to be effective
      immunomodulators in physical load.

PMID- 9265468
TI  - [14th improving course in rythmology. La Grande Motte, France, June 27-29, 1996].

PMID- 9265469
TI  - [Antagonists of the tachykinin receptors].
AB  - Antagonists of the tachykinin receptors, which have been most widely used in
      scientific investigations during the past decade (up to 1995 inclusive), are
      reviewed. The structures and peculiar characteristics of peptide and nonpeptide
      compounds of this class are described. Applications of these antagonists in the
      search for new subtypes of tachykinin receptors and for structure-function
      studies are discussed.

PMID- 9265470
TI  - [Genes of plant Ser/Thr protein phosphatases: detection of sequences related to
      PPT/rdgC].
AB  - An unknown sequence that may encode a fragment of the Ser/Thr protein phosphatase
      (designated PP6Zm) related to PPT/rdgC phosphatases was identified using PCR on
      maize genomic DNA. A dbEST search using a partial amino acid sequence of PP6Zm
      revealed a putative homolog of PP6Zm expressed in Arabidopsis thaliana (EMBL
      AT6726). A search of the SwissProt database indicated that the partial amino acid
      sequence of AT6726 has the highest identity (54.3%) to the rdgC phosphatase from
      Drosophila melanogaster. The maize phosphatase PP1Zm6, described previously as a
      PP1 isoform (EMBO J., 1993, vol. 12, p. 3497), was found by us to be plant
      homolog of mammalian PPT. In addition, six fragments of new (pseudo) genes
      homologous to the phosphatase genes encoding PP1, PP2A, and PPX isoforms were
      detected in the maize genome. The existence in maize of a multigene PP2A family,
      reported only for dicotyledons, and of a PP1 multigene family, found earlier in
      both di- and monocotyledons, was shown.

PMID- 9265471
TI  - [Construction of artificial genes by PCR methods using the synthetic template].
AB  - Artificial genes were synthesized by the PCR method. Single-stranded DNA
      contained in an unpurified mixture of oligodeoxynucleotides after automated
      synthesis was used as a template. The features of this approach were studied.

PMID- 9265472
TI  - [Artificial ribonucleases I. Targeted RNA cleavage by 5'
      peptidyloligodeoxyribonucleotides containing arginine and leucine residues].
AB  - The interaction of DNA and RNA with oligodeoxyribonucleotides and their 3'
      terminal N-(2-hydroxyethyl)phenazinium derivatives carrying peptide residues with
      alternating basic and hydrophobic amino acids at the 5'-terminal phosphate was
      studied. It was found that the introduction of peptide residues (LeuArg)n-Gly-NH2
      (n = 2-4) into an oligodeoxyribonucleotide enhances the latter's hybridization
      ability: each additional LeuArg pair increases the Tm value of the
      (5')pd(CACACACAAAAAAC).(3')d(TGTGTGTG)p(-LeuArg)n-Gly- NH2 complex by 1.3 degrees
      C. The reagents did not destort the DNA structure and were capable of site
      specific hydrolysis of the phosphodiester bonds of RNA. It was shown that the
      location of the cleavage sites and the efficacy of the RNA hydrolysis at n = 2
      and 4 and at n = 3 strongly differ. The maximum hydrolysis (80%) of
      tetradecaribonucleotide (5')p(GAUUGAAAAUCCCC) was achieved using
      peptidyloligodeoxyribonucleotide (3')d(CTAACT)p(LeuArg)4GlyNH2. The possibility
      of directed cleavage of phosphodiester bonds in tRNAPhe by
      peptidyloligodeoxyribonucleotides (3')d(CTAACT)p(LeuArg)nGlyNH2 (n = 3 and 4) was
      shown.

PMID- 9265473
TI  - [Algae polysaccharides. 51. Study of sulfated galactan of red algae Laurencia
      coronopus J.Ag. (Rhodophyta, RLhodomelaceae using partially reductive
      hydrolysis].
AB  - The structure of the agarlike sulfated galactan from the epiphytic red alga
      Laurencia coronopus was elucidated by partial reductive hydrolysis. In the
      presence of borane-4-methylmorpholine complex, the acid-labile glycosidic
      linkages of 3,6-anhydrogalactose residues of the polysaccharide are hydrolyzed
      with the simultaneous reduction of these residues, thus precluding their further
      acidic degradation. The main products of this hydrolysis were 3,6-anhydro-4-O
      beta-D-galactopyranosyl-L-dulcitol (agarobiitol), its 6-O-methyl derivative,
      agarobiitol 6-sulfate, and some higher oligosaccharides. These products were
      structurally analyzed by composition, mass spectrometry, and NMR.

PMID- 9265474
TI  - [Synthesis of triterpene 2-deoxy-alpha-D-hexopyranosides on the basis of glycals
      and their effect on reparative processes].
AB  - Triterpene 2-deoxy-alpha-D-hexopyranosides were synthesized by the glycosylation
      of oleanane triterpene alcohols with D-glucal and D-galactal acetates in the
      presence of di(sym-collidine)iodonium perchlorate with subsequent deiodination
      and deacetylation of the resulting 2-deoxy-2-iodo-alpha-D-glycosides. 2-Deoxy
      alpha-D-arabino- and -lyxo-hexopyranosides of methyl glycyrrhetinate demonstrated
      pronounced antiulcer activity and stimulated reparative skin regeneration in rats
      more effectively than glycyrrhizic acid and methyluracil.

PMID- 9265475
TI  - [Fast DNA amplification in small ultrathin-wall microplates].
AB  - A new method was developed for fast DNA amplification by polymerase chain
      reaction in tiny ultrathin microplates formed directly on the thermocycler's
      thermoblock. The microplates are made from thin (40-60 microns) polypropylene
      film by the thermal vacuum-formation method. Due to the effective heat transfer
      to 10-15 microliters samples and a high velocity of heating and cooling of the
      thermoblock (up to 7 degrees C/s), the total duration of the DNA amplification
      (30 cycles) is only 15-30 min.

PMID- 9265476
TI  - Nurse education to improve.

PMID- 9265477
TI  - Universal precautions to become standard: infection control news brief.

PMID- 9265478
TI  - Computer technology and nursing: demystifying cyberspace.
AB  - This is the first in a series of articles which aims to explore the impact of
      computer technology on nursing and nursing practice. In this article, the history
      of the development of computers is summarised and terminology associated with
      computer use defined and explained, as well as the basic uses of computer
      programs. In subsequent articles the development of health-information systems
      will be explored, along with their impact on nursing practice. In addition, the
      use of computer technology to inform all areas of nursing practice and education
      will be discussed in light of the voluminous information now available worldwide,
      literally at one's fingertips, via the Internet and the World Wide Web.

PMID- 9265479
TI  - National Library of Australia network services.

PMID- 9265480
TI  - Sensory attributes of craved and aversive foods in healthy women.
AB  - This article is an edited version of a paper presented at the Sigma Theta
      International Nursing Research Congress in Madrid, Spain on June 22, 1993. It
      explores sensory characteristics of craved and aversive foods in healthy women.
      Typically, cravings characterised as intermittents, sweet-tasting and pleasant
      smelling. Aversions continuous, bad-tasting and unpleasant-smelling. Women
      reporting aversions tend to it less body mass than women without aversions: p <
      0.06. The data suggest that craved aversive foods may exert unequal effects and
      that sensory characteristics may provide cues the formation of cravings and
      aversions. These early findings guide health-care practitioner in helping
      individuals to improve their nutritional intake.

PMID- 9265481
TI  - Establishing a transcultural nursing development unit: the south-western Sydney
      experience.
AB  - Nursing development units (NDUs) have been established in the United Kingdom and
      the United States, with the aim of developing excellence in nursing practice, in
      practice settings and with practising nurses. This paper describes the adaptation
      of this concept to an Australian context, in an area where a diverse ethnic
      population challenges nurses to accommodate cultural differences and to provide
      accessible, culturally-sensitive health care.

PMID- 9265482
TI  - The physical and mental health of men.

PMID- 9265483
TI  - Report review: superspecialty service guidelines for acute cardiac interventions.

PMID- 9265484
TI  - Nurses and euthanasia--some issues.

PMID- 9265485
TI  - Comment on injection study.

PMID- 9265486
TI  - Consultant aboriginal liaison midwife.

PMID- 9265488
TI  - Conference review--stories from the field: nursing and methodology.

PMID- 9265489
TI  - The social and gender composition of nursing students in Australia: a comparison
      between 1987-1990 and 1995 recruits.
AB  - This national study compares the social and gender characteristics of an earlier
      group of 1551 students in higher-education programs in 1987 and 1990 with the
      national study group of 2295 students sampled in 1995. Using a specially
      constructed socio-economic variable for comparison, the analyses demonstrated a
      significant difference in the socio-economic level of the household for the
      female but not the male group. There was a significant difference in the
      proportion of males entering nursing between the earlier and latter groups.
      Further, in the latter group, these males were more likely to enter nursing
      programs directly from school. Members of the female group in the latter sample
      were more likely to have attended a school in a less populated area, come from
      households with a reduced family size, have mothers who were earning an income
      and have mothers who had achieved a higher level of education than was found in
      the earlier group. Logic analysis revealed that there was a significant
      interaction between the household variables, socio-economic status, number of
      siblings and income received by the mother of the respondents in the early and
      latter groups for females but not for males. This interaction for the female
      group, plus the finding that members of the latter group were more likely than
      other university students to defer their Higher Education Contribution Scheme
      (HECS) payments, suggests that if politicians were to make changes to the HECS it
      may affect the delicate social balance currently achieved in nursing recruitment
      in Australia.

PMID- 9265487
TI  - A snapshot of Australian nursing scholarship 1993-1994.
AB  - This study investigates Australian nursing academics' publications in nursing and
      health journals in 1993-94. It describes the personal and professional
      characteristics of the authors, characteristics of the articles and interactions
      among these characteristics. Frequency descriptions were done to describe data
      and cross-tabulations were used to investigate relationships. The major findings
      about the authors are that few nurse-academics are publishing, that those who do
      publish are mainly senior academics, and that there are differences in
      publication rates among the states. The major findings about articles were that
      the majority of articles were in domestic journals, the major type of scholarship
      is research scholarship and that there is a shift away from teaching scholarship
      articles. The major focus of research scholarship is medical-surgical-nursing,
      with a quantitative approach, correlational design, convenience sample and no
      theoretical framework. Recommendations are made for further research which does
      not restrict scholarship to that appearing in journals and which investigates
      factors that constrain and facilitate scholarship.

PMID- 9265490
TI  - Infection control brief: is CJD the human face of 'mad cow disease'?

PMID- 9265491
TI  - Report from the Australian Health Ethics Committee: ethical concerns related to
      organ transplantation.

PMID- 9265492
TI  - Nursing-related information and data: what is the role of computers in nursing
      practice?
AB  - This is the final article in a series which examines the impact of computer
      technology on nursing and nursing practice. In it we briefly explore the concept
      of informatics and the role of a unified nursing language in data collection and
      statistical comparisons.

PMID- 9265493
TI  - Alcohol and other drug problems in Australia: the urgent need for nurse
      education.
AB  - The economic, social and health costs associated with alcohol and other drug use,
      including medicines, impact on the Australian community profoundly. Many
      Australians use alcohol and other drugs (AODs) on a regular basis and a
      significant number experience problems at some time. There are about 25,000 drug
      related deaths annually, the majority of which are related to alcohol and tobacco
      use. Many young people die or are injured as a direct result of alcohol
      intoxication, accidental overdose and related problems, and significant numbers
      of elderly people are hospitalised, permanently incapacitated or suffer avoidable
      trauma through adverse drug reactions and side-effects of medications. It is
      estimated that at least 25 per cent of acute hospital beds hold patients with
      alcohol-related problems directly associated with the medical diagnosis, and
      there are comparable numbers of people needing social and other forms of
      assistance at some time. Despite the preventative nature of many AOD problems and
      the call for harm reduction, timely intervention and support for the thousands of
      Australians attending hospitals, community health and mental health services,
      nurses are yet to effectively assist the community in preventing and responding
      to the range of AOD problems. Nursing policy, guidelines and clinical expertise
      are required to assist the community in addressing this issue. Undergraduate,
      postgraduate and continuing education have a vital role to play in providing the
      profession with the knowledge, skills and research base to meet this challenge.

PMID- 9265494
TI  - Accommodating euthanasia?

PMID- 9265495
TI  - Double up for real protection.

PMID- 9265496
TI  - The role of nurses in cardiopulmonary resuscitation and defibrillation.
AB  - Cardiac [corrected] arrest outcome studies have identified early defibrillation
      (among other variables) as a strong predictor of survival--with the emphasis
      placed on minimal delay between arrest and 'shock'. Nurses play a key role in the
      management of in-hospital cardiac arrest. Often they are first on the scene of an
      arrest--initiating cardiopulmonary resuscitation (CPR) as well as summoning
      assistance from the 'advanced life support'/'arrest' team. Thus it is argued that
      nurses should be willing (and able) to perform defibrillation when required.
      Notwithstanding this, the community has an expectation (rightly or wrongly) that
      all nurses are able to appropriately manage a collapse situation. However,
      research clearly demonstrates that not all nurses are competent in CPR. There is
      obviously a mismatch between community expectations and reality, which nursing
      needs to address. Nurses can contribute to the prevention of cardiac arrest in
      the community by promoting the importance of seeking medical care in the event of
      chest pain. Furthermore, skilled clinical assessment and recognition of the
      prodromes of cardiorespiratory collapse may reduce the incidence of in-hospital
      cardiac arrests.

PMID- 9265497
TI  - Australian Institute for Suicide Research and Prevention.

PMID- 9265498
TI  - Conference review--inaugural Australian Pain Society nurses pain seminar: 'pain
      and suffering--challenges, concepts and creativity'.

PMID- 9265499
TI  - A profile of nurse-academics in Australian universities.
AB  - This study investigates qualifications, level of employment, state and territory
      differences, and gender of nurse-academics in Australian universities. It
      describes these personal and professional characteristics and the interactions of
      some characteristics. Frequency descriptions were done to describe data, and
      cross-tabulations and analysis of variance were used to investigate
      relationships. The most significant findings were that not enough nurse-academics
      are qualified at the doctoral level, and nurse-academics are underrepresented at
      senior levels in comparison with all Australian academics. Recommendations for
      strategies to encourage and facilitate suitably qualified nurse-academics to
      undertake doctoral study are made.

PMID- 9265501
TI  - Human recombinant anti-Rh(D) monoclonal antibodies: improvement of biological
      properties by in vitro class-switch.
AB  - Therapeutic use of human monoclonal antibodies has so far been hampered by their
      poor availability. Recent developments in recombinant DNA technologies are
      expected to fill this gap; the variable and constant sequences of antibodies can
      be selected independently and then subsequently joined to express whole
      antibodies. We assessed here the potential of this methodology to obtain novel
      anti-D antibodies with improved biological characteristics. The sequences coding
      for heavy and light chains of two anti-Rh(D) monoclonal antibodies (one IgG1 and
      one IgG3) were isolated and co-expressed into murine myeloma cell P3X63.Ag8.653,
      either directly (parental antibodies) or after exchange of constant heavy chain
      sequences (class-switched antibodies). Parental antibodies produced either by
      transfectomas or by hybridomas behaved similarly in analysis of biochemical,
      binding and effector properties. Class-switched antibodies displayed altered
      functional properties over parental antibodies. Of particular interest, one of
      them showed improved phagocytosis potencies over both parental antibodies.
      Additionally, these results indicate that functional properties do not always
      simply reflect the addition of properties of constant and variable parts but that
      interactions between constant and variable regions may interfere.

PMID- 9265500
TI  - Humanization of a mouse antibody against human alpha-4 integrin: a potential
      therapeutic for the treatment of multiple sclerosis.
AB  - alpha 4 beta 1 integrin (VLA-4) is crucial for the adhesion of leukocytes to
      human vascular cell adhesion molecule-1 (VCAM-1) on inflamed endothelium. This
      cell adhesion event is the first step in leukocyte extravasation across the blood
      brain barrier in inflammatory diseases of the central nervous system (CNS) such
      as experimental autoimmune encephalomyelitis (EAE). Prevention of leukocyte
      infiltration by antibodies against the alpha 4 integrin, which block the alpha 4
      beta 1 integrin/VCAM-1 interaction, have been shown to suppress clinical and
      pathological features of EAE. In this study, two mouse monoclonal antibodies
      (MAb) directed against human alpha 4 integrin were analyzed in vitro for their
      ability to block the interaction of leukocytes with VCAM-1 under different assay
      conditions. The best blocking MAb, AN100226m, was humanized by complementarily
      determining region grafting, associated with human C regions and expressed. We
      found that modification of two structural determinants (H27 and H29) for the
      heavy chain CDR1 loop in one hand, and modification of framework amino acid H38,
      H40 and H44 in the other hand, had no effect on antigen binding. In contrast,
      modification of a structural determinant (H71) for the heavy chain CDR2 loop
      resulted in loss of binding. The humanized antibody. AN100226, was equivalent to
      the murine antibody. AN100226m, in binding to alpha 4 beta 1 integrin and in
      blocking cell adhesion. More importantly, AN100226 was as effective as AN100226m
      in the reversal of active EAE in guinea pigs and thus may be useful in the
      treatment of autoimmune diseases such as multiple sclerosis. AN100226 is
      currently in phase II clinical trials in the UK for the treatment of multiple
      sclerosis exacerbations.

PMID- 9265502
TI  - Incorporation of T cell counterparts in the fusion partners for generation of
      human monoclonal antibodies from Staphylococcus aureus stimulated B lymphocytes.
AB  - B cell growth and differentiation into immunoglobulin secreting cells is
      controlled by various cytokines and cell to cell contact with T cells. Fusion
      partner for human hybridoma therefore should accommodate all or some of these
      signaling systems to overcome the unique situation of MHC incompatibility, need
      for specific growth factors simultaneously taking into consideration the
      downstream processing of the product for the clinical use. We have thus directed
      our efforts towards the development of a fusion partner which would not need
      Epstein-Barr virus transformation of B cells prior to fusion. A nontransforming
      mitogen, formalinized Staphylococcus aureus (FSTA) was used for stimulating human
      B cells. Successful production of human IgM monoclonal antibody was achieved by
      incorporating Jurkat-4 cells in existing mouse human heterohybrid through fusion
      of these cells followed by fusion with human B cells. To accommodate chromosomes
      of both T and B cells after fusion, human myeloid precursor cells KG1a, and to
      incorporate T cell, HuT78 cells were fused. CD34+ and CD4+ hybrid of KG1a and HuT
      78 cells-434 AM-when used as fusion partner could allow secretion of MAbs,
      however growth potential was low. SP2/0 cells were then incorporated in 434 AM
      cells to give myeloma environment to fused human B cells. Rabies virus
      neutralizing human IgG MAb secreting clone was generated by fusing FSTA
      stimulated human B cells with this fusion partner.

PMID- 9265503
TI  - Receptor analysis of idiotype antibodies derived from MALT type B-cell lymphoma
      hybridomas.
AB  - The generation of human antibodies derived from extranodal MALT type B-cell
      lymphomas allows to evaluate steps in their pathogenesis as well as to establish
      potential immunological therapies. Intraclonal diversity and the existence of
      bystander nonmalignant B-cells outline the need for reliable identification of
      the tumor immunoglobulin representing hybridomas. Human heterohybridomas were
      generated from five cases of MALT type B-cell lymphomas (4 low grade, one high
      grade) by the fusion of lymphoma B-cells with the murine myeloma cell line NSO
      and tested for isotype identity with the tumor. RT-PCR using VH Fr1/JH primers
      was performed with RNA of tumors and hybridomas that share the same isotype with
      the tumor. PCR-products were sequenced directly. In each case lymphomas were
      hybridized with a comparable fusion efficiency. DNA sequence analysis of the
      immunoglobulin heavy chain identified one or more hybridomas derived from the
      tumor. However some other hybridomas which share the same isotype with the tumor,
      may be different in their VH family or their sequence. Hybridomas can be used as
      a tool for the research on the MALT lymphoma immunoglobulin receptor. For the
      identification of tumor immunoglobulin, secreting hybridomas sequencing and the
      check of molecular identity is indispensable after isotype determination.

PMID- 9265505
TI  - Synergy between anti-CD40 MAb and Epstein-Barr virus in activation and
      transformation of human B lymphocytes.
AB  - For human B lymphocytes, Epstein-Barr virus (EBV) is a polyclonal activator,
      inducing both proliferation and Ig secretion. It is also a transforming virus
      capable of generating immortalized B cell lines. These early and late functions
      of EBV are not apparently connected. The receptor for EBV, CD21, also serves as a
      receptor for some complement components and is called CR2. This molecule
      associates with CD19 and TAPA-1 on the surface of B cells. This complex is
      involved in signaling B cells and participates in many responses. We have
      observed that simultaneous ligation of CD40 and the CD21 complex, by exposure to
      anti-CD40 MAbs and EBV, enhances both the short-term proliferation as well as the
      long-term transformation rate of human B lymphocytes. B cell proliferation shows
      synergy between anti-CD40 MAb and EBV. CD19 also appears to be involved in the
      synergistic activation of B cells through CD40 and CD21, since ligation of CD19
      with anti-CD19 MAbs, either prior to or concomitant with exposure to anti-CD40
      and EBV, markedly inhibits both proliferation and subsequent B cell
      transformation. These observations do not elucidate the mechanisms of B cell
      transformation employed by EBV but the do suggest a relationship between early
      proliferation and later transformation induced by the virus. Anti-CD40 enhances
      both these effects and anti-CD19 is capable of inhibiting both.

PMID- 9265504
TI  - Full-scale 'naive' human antibody repertoires assembled from VH and VL variable
      regions.
AB  - Very large 'naive' human antibody repertoires have been obtained from RT-PCR
      cloned VH and VL variable regions. They are used as starting material for the
      assembly of medium sized combinatorial libraries or so called multicombinatorial
      libraries. In nonimmunized individuals immunoglobulin messenger RNAs are poorly
      expressed, which can be a serious limitation for cloning efficiency. To overcome
      this problem two complementary strategies have been used: a nonspecific
      polyclonal activation of B cells, and a secondary PCR amplification technique to
      ensure recovery of Ig messengers in large amount and without introducing any
      bias.

PMID- 9265506
TI  - Unregulated care workers ... the thin edge of the wedge.

PMID- 9265507
TI  - Dangerous liaisons: thinking, doing, nursing.

PMID- 9265508
TI  - Restraint: some legal implications.
AB  - The law in relation to the autonomy and physical integrity of persons is explored
      in this paper. Charges of assault and battery may result where trespass to the
      person--that is, unwanted physical contact--occurs. These concepts are discussed
      in the context of the use of restraining behaviours applied to persons in health
      care facilities.

PMID- 9265509
TI  - International collaboration among researchers: a case study in mental health
      services research.

PMID- 9265510
TI  - Organ donation ... how do we ask the question?

PMID- 9265511
TI  - Preliminary evaluation of the effects of a nutrition awareness project on the
      Ngaanyatjarra Pitjantjatjara Yankunytjatjara communities of central Australia.
AB  - Preliminary observations from one nutrition awareness project--Approaches to
      Failure to Thrive--in progress in the Ngaanyatjarra Pitjantjatjara
      Yankunytjatjara region of central Australia are discussed, current strategies are
      listed and the need for multi-faceted solutions emphasised. A more rigorous
      quantitative evaluation is recommended, within the constraints of funding and
      access to data.

PMID- 9265512
TI  - Quality use of medicines for people with diabetes.

PMID- 9265513
TI  - Hand washing--the difference between harm and healing?

PMID- 9265514
TI  - Web-site review.

PMID- 9265515
TI  - New threats to community/public health nursing in Australia.

PMID- 9265516
TI  - Unregulated health workers.

PMID- 9265517
TI  - On the issue of patient non-compliance.

PMID- 9265518
TI  - Conference review: 'towards self-management of asthma--whose asthma is it
      anyway?'.

PMID- 9265519
TI  - Nursing and health in Indonesia.

PMID- 9265520
TI  - The challenges of cuts to education: whither nursing education?

PMID- 9265521
TI  - Into the new paradigm: writing the script for the future of health care.
AB  - The world is changing dramatically, driven by changes in technology and global
      shifts beyond the control of anyone. The requisite of the leader will be to focus
      on the changes and translate them in ways that provide meaning and direction for
      the future. Critical to this process is the ability to embrace the emerging
      reality and to apply its principles to the delivery of health services. The rules
      that once applied to our thinking and acting in health-service provision no
      longer apply. The job of leadership is to understand the meaning of the changes
      and to build appropriate responses to them. Whatever the response, it will
      fundamentally alter the way in which we see health-care delivery and how we
      provide services for the immediate future. The notion of value and its
      application to the changing health system is central to the change activities and
      provides the context for any and all changes in the way health service is
      conceived and provided for in the foreseeable future.

PMID- 9265522
TI  - The legal framework for mental health nursing.
AB  - This article sets out basic legal principles underlying the care and treatment of
      mentally ill clients. Legal considerations are important for nurses, because it
      is now felt that the care of the mentally ill is as much a legal matter as a
      medical one. The frequent ordering of compulsory care, detention and
      administration of medication takes place in a climate of ever-increasing emphasis
      on autonomy, and has resulted in the need for nurses to ensure that they do not
      violate clients' human and legal rights. Legislation is concerned not primarily
      with the finer points of what mental illness is--that is left to the medical
      profession--but with criteria which warrant the detention and treatment of a
      person against their will. The article points to international documents which
      set out principles for the care of the mentally ill, as well as both
      Commonwealth, state and territory legislation. It summarises the main provisions
      of these in relation to involuntary detention and treatment, as well as
      electroconvulsive therapy and psychosurgery. Nurses who care for mentally ill
      clients need, therefore, to understand in some detail the legislation that
      applies to them in their professional capacity, as well as the human rights it
      seeks to protect.

PMID- 9265524
TI  - Nurse practitioner stage three report.

PMID- 9265523
TI  - Nursing on the electronic highway.
AB  - Notes prepared by Helen Hamilton, Lois Hazelton and Keith O'Brien, from a paper
      presented by Dr Kathleen McCormick at Royal College of Nursing, Australia's
      National Forum, Canberra in May 1996. The original paper identified the
      potential, current trends and applications of electronic technology, and also
      discussed some of the difficulties and barriers to realising the full potential
      of this technology in health care, education and research.

PMID- 9265525
TI  - Successful implementation of a no-smoking policy.
AB  - Literature suggests that positive behavioural changes occur among employees after
      the introduction of a no-smoking policy (NSP). This paper reports successful
      results following the introduction of a revised NSP at Hawker de Havilland
      Victoria (HDHV) Limited, an aerospace component manufacturing company. In
      February, 1994 a poll survey indicated that 86 of the 480 employees smoked. In
      April, 1994 all 480 employees were surveyed, to assess smoking behaviour and
      attitudes. Education programs and company-sponsored Fresh Start Quit courses were
      conducted on-site. In August, 1994 a second survey was distributed, to the
      smokers only, to assess smoking habits, behaviour, satisfaction with the NSP and
      whether education programs influenced them to change their smoking habits.
      Findings in this study suggest that the introduction of the NSP and education
      programs induced positive behavioural and attitudinal changes to smoking. In
      August, 1994 the key results of the second smoking survey indicated that 5 per
      cent of employees quit smoking, 43 per cent reduced the number of cigarettes
      smoked per day, 1.6 per cent smoked more and 30 per cent reported no change.
      These results show that a short-term multifaceted smoking cessation program
      implemented over 5 months can produce a decrease in cigarette smoking.

PMID- 9265526
TI  - MRSA--down but not out.

PMID- 9265527
TI  - More on nursing scholarship.

PMID- 9265529
TI  - Conference review--research issues in rural and remote area health services.

PMID- 9265530
TI  - [Role of radiotherapy in the management of adenocarcinoma of the breast
      accessible to conservative surgery].
AB  - Standard treatment for limited stage adenocarcinoma of the breast includes
      lumpectomy (or a quadrantectomy), axillary node dissection, regional radiation
      therapy and, if the prognostic factors are unfavourable, chemotherapy and/or
      hormone therapy. This is supported by the results of American and European
      randomised trials. There have been many attempts at improving the modalities of
      conservative surgery and postoperative radiation therapy in order to maximize
      local control and minimize late sequellae. It is also likely that induction
      chemotherapy and external beam radiotherapy applied in selected cases increase
      the proportion of patients who can be offered conservative surgery.

PMID- 9265531
TI  - [Biological basis of combined chemo-radiotherapy. Applications to lung cancers].
AB  - Radiation therapy has been for years the treatment of choice of locally advanced
      non small cell lung cancer. Improvement due to the combination of radiation and
      chemotherapy has been shown recently through several randomized trials and a
      recent meta-analysis. These results may be explained by biological mechanisms,
      yet uncompletely explored, which are detailed in this review and applied to lung
      cancer. The optimal combination scheme is not yet defined, even though the
      concurrent approach is promising, at the expense of an increased toxicity which
      is the limiting factor of treatment escalation doses. Biological findings and
      future results of randomized trials will hopefully open new avenues in the
      therapeutic strategy of this poor prognosis disease.

PMID- 9265532
TI  - [Adjuvant radio-chemotherapy of cancers of the rectum].
AB  - Since several years, surgery has been the gold standard for the treatment of
      stage B2 and C rectal cancer. Following high-quality surgery, local recurrences
      occurred in 24 and 53% of the cases, respectively. The adjuvant treatments is
      aimed at decreasing the probability of local recurrence and at increasing
      survival rates. While postoperative radiation therapy eradicates residual disease
      in these tumors, preoperative radiation therapy may also decrease the tumoral
      volume in order to make surgery easier. The improvement in radiation modalities
      has allowed an increase in the treatment dose with minimal side-effects. Several
      clinical studies have demonstrated the efficacy of pre- or postoperative
      radiotherapy. The objective of the combination of radiation and chemotherapy is
      to increase the local control and decrease the metastatic process. Chemotherapy
      associated with postoperative radiotherapy leads to better results than surgery
      alone or radiation therapy plus surgery, in terms of overall survival rates and
      disease-free survivals. Encouraging clinical trials using the preoperative
      combination have permitted the implementation of phase III studies that are still
      in progress. Although optimal modalities related to chemotherapy are still not
      clearly defined, the importance of each modality is discussed, particularly in
      regard to the combination of radiation and chemotherapy.

PMID- 9265533
TI  - [Radium therapy from birth to death. 1896-1976].

PMID- 9265534
TI  - [Adjuvant radiotherapy after radical prostatectomy. Apropos of a series of 73
      patients in Lyons (France)].
AB  - PURPOSE: Descriptive analysis of adjuvant radiation therapy after radical
      prostatectomy. MATERIALS AND METHODS: From 1986 to 1993, 73 patients (median age,
      64.5 years; Gleason score > or = 7 : 36 pts; T1:22; T2:40; T3:11) were included
      into the study. On the operative specimen, the cancer grades were pT2:5
      (involvement of the apex), pT3:67, pT4:1, pN1-2:8. Radiation therapy was
      performed after a mean resting period of 112 days. The target volume was the
      prostatic area. The technique used was a four-field box with an 18 MV-X photon
      beam. The dose was 50 Gy/20 fractions/5 weeks. No hormonal treatment was
      administered, except for 5 patients for a short duration. RESULTS: The median
      follow up was 46 months. One anastomotic local failure was salvaged by trans
      urethral resection, three distant metastatic failures. Out of 72 patients with a
      PSA < 3 ng/mL at the end of radiotherapy, 13 showed an isolated elevation. The 5
      year overall survival rate was 93%. The event-free survival was 72% after 5
      years. Pathological differentiation and Gleason score were significantly
      correlated with the survival. There was no complication related to radiotherapy.
      CONCLUSION: Elective adjuvant radiation therapy for pT3 prostate adenocarcinoma
      after radical prostatectomy provides a good local control with minimal morbidity.

PMID- 9265535
TI  - [Medulloblastoma in adults. Val-de-Grace hospital experience (1975-1994) and
      literature review].
AB  - PURPOSE: Retrospective analysis of prognostic factors in a series of 14 adult
      patients presenting with medulloblastoma treated by surgery and subsequent
      radiotherapy. PATIENTS AND METHODS: Thirteen male and one female patients (mean
      age, 27 years; range 20-40) presenting with medulloblastoma were treated at the
      Val-de-Grace hospital from 1975 to 1994. The mean delay between the initial
      symptoms and the diagnosis was 17 weeks (range, 2-76). The tumor was median in
      three cases, lateral in seven, and median and lateral in four. Eleven
      medulloblastomas belonged to the classical subtype and three others to the
      desmoplastic type. Patients were treated by surgery followed by external
      radiation therapy. The ablation was complete in four cases and incomplete in ten
      cases. RESULTS AND CONCLUSION: Five- and ten-year overall survival rates were 63
      and 25%, respectively. There was a trend toward a higher probability of survival
      for older patients (ie, for patients above 26 years of age) presenting with a
      desmoplastic central tumor treated by complete surgery and subsequent post
      operative radiotherapy. Results are discussed in regard to the literature.

PMID- 9265536
TI  - [Hyperfractionated reirradiation after salvage surgery in cervico-facial
      carcinoma. Result of a pilot study in 14 patients].
AB  - PURPOSE: Between November 1988 and May 1992, 14 patients were enrolled in a pilot
      study to evaluate the feasibility and results of hyperfractionated reirradiation
      for the treatment of head and neck recurrences or of second primary tumors
      developed in a previously irradiated volume. MATERIALS AND METHODS: All patients
      underwent a surgical resection for the treatment of their recurrence or second
      cancer. Reirradiation was proposed because of positive margins and/or lymph node
      metastasis with extra-capsular spread. The planned reirradiation dose was 60 Gy
      over 5 weeks, with two daily fractions of 1.2 Gy delivered 6-8 hours apart.
      RESULTS: Of the 14 patients, 10 received the reirradiation scheduled dose (ie, 60
      Gy). All patients experienced an acute mucositis that never led to disruption of
      the treatment. Ten patients died 3 to 41 months after reirradiation (mean: 14
      months), three were disease-free 48 to 71 months after reirradiation and one was
      alive with local progressive disease 74 months after reirradiation. The overall
      local control rate within the reirradiated volume was 43%. The 24- and 36-month
      overall survival rates were 50 and 35%, respectively. Overall, 13 late
      complications were noted: four were grade 1, seven were grade 2, and two were
      grade 3. Three patients still alive in September 1993 and whose initial files
      were available were enrolled in an additional study to assess from dose-volume
      histograms the cumulative doses delivered by the two irradiations. CONCLUSION:
      Despite poor local control, reirradiation using a hyperfractionation schedule
      with high dose level is feasible in terms of acute and late toxicity.

PMID- 9265537
TI  - [Optimization of dose distribution of radiation in cancers of the cavum:
      association of an expert-system and a mathematical algorithm].
AB  - Optimization of radiation therapy in nasopharyngeal carcinoma is particularly
      complex due to both the proximity of at risk organs and the high dose that has to
      be delivered. To obtain an optimal dose distribution, a knowledge-based
      optimization technique has been designed that associates an expert-system, named
      CAVCAV, with numeric optimization (gradient projection method). Based on clinical
      and physical criteria, CAVCAV determines the geometric characteristics of the
      radiation fields (beam direction, location and shape of the shielding blocks) for
      the three stages of radiation therapy of nasopharyngeal carcinomas. Stage 2
      treatment fields proposed by CAVCAV, though not perfectly adapted to the patient,
      are mathematically (beam weights, beam directions, isocenter position) and
      geometrically (adaptation of fields and shape of blocks by virtual simulation)
      optimized.

PMID- 9265538
TI  - [In vivo dosimetry for the evaluation of the irradiation dose for the thyroid
      after prophylactic cerebral irradiation in leukemia of children].

PMID- 9265539
TI  - [Report of the 38th meeting of the American Society for Therapeutic Radiology and
      Oncology (ASTRO), Los Angeles, 27-31 October 1996].

PMID- 9265541
TI  - Infection control brief: dilemma of the decade--re-use of single-use medical
      devices.

PMID- 9265540
TI  - [European Society for Therapeutic Radiology and Oncology (ESTRO) Vienna
      (Austria), September 23-26 1996].

PMID- 9265542
TI  - The 'Health Promoting Schools' strategy: implications for nursing and allied
      health professionals.
AB  - In 1993, the Commonwealth government officially recommended that schools were
      excellent places in which to promote better health as part of the proposed
      National Health Strategy. The concept of Health Promoting Schools (HPS) has
      recently been endorsed by the Department of Education, with the result that
      teachers are now expected to further expand their role and responsibilities in
      this area. This paper outlines a survey of infant and primary school teachers in
      New South Wales (n = 350) which, amongst other factors, ascertained teachers'
      perceptions of the assistance they needed from school and community nurses in
      order to effectively implement the HPS strategy. Results demonstrated that
      teachers have a fundamental lack of understanding of child health issues and the
      HPS strategy, and that an overwhelming call by teachers for assistance from the
      nursing profession has implications not only for nurses but also for allied
      health agencies and the tertiary sector.

PMID- 9265543
TI  - Public misled on tampon-related toxic shock syndrome.

PMID- 9265544
TI  - The use of dilemma situations to analyse industrial action by nurses.
AB  - Traditionally, the history of nursing has emphasised sacrifice and the obligation
      to care, placing limits on the way that nurses could argue for improved
      conditions and status. However, over the past decade nursing has changed
      significantly both in terms of its educational system and in respect of the
      context in which nurses now work. In an increasingly technological environment,
      nurses now seem more ready to consider the industrial actions that other
      professions take. The present study measures the particular orientation to care
      (personal or technical) that nurses currently hold and then looks at whether this
      orientation has an effect on nurses' industrial activism, and the degree of
      difficulty felt by nurses when faced with choosing between industrial options.
      Orientation to care was measured through the choice of actions in a series of
      behaviours which were pre-rated as to whether they primarily involved technical
      or personal care. Industrial activism was measured through a series of vignette
      situations, with behavioural options ranging from low to high activism. Results
      of the study demonstrated that a particular orientation to care does in fact
      impact on industrial activism and difficulty scores. Overall, the results of this
      study demonstrated, firstly, that nurses who preferred to express their care in a
      personal rather than a technical manner were more ready to take industrial
      action. Secondly, those nurses who held a strong duty of care towards their
      patients were less ready to take industrial action than those who considered
      workers' rights as the more important issue. However, at the same time, nurses
      who held a strong duty of care had more difficulty in choosing between options.

PMID- 9265545
TI  - Nurses as exemplars for health--do we take it seriously?

PMID- 9265546
TI  - "Is it still as easy as picking up the phone?" The impact of computers on how we
      communicate.
AB  - This is the second in a series of articles which aims to explore the impact of
      computer technology on nursing and nursing practice. In this article, the
      relationship between the major players in the computer leagues today is briefly
      explored, and attempts made to demystify the use of computers in electronic
      communication. The establishment of electronic networks is explained and there is
      an introduction to the fastest growing network in the world--the World Wide Web.

PMID- 9265547
TI  - Accreditation goes bush.

PMID- 9265548
TI  - Green activism and the profession of nursing: an essential connection.

PMID- 9265549
TI  - Satisfaction with nursing home care of a relative: does inviting greater input
      make a difference?
AB  - This study examined whether a formal invitation to have greater involvement in
      the nursing home care of their relatives resulted in increased satisfaction in
      former care-givers. The conceptual framework guiding the study was based on Roy's
      Adaptation model of Nursing (Roy 1984, 1989), since it was believed that the
      intervention might aid the adaptation of family members to the
      institutionalisation of a close friend or relative. Increased satisfaction with
      care was measured as evidence of adaptation. In the study, 31 former care-givers
      were randomly assigned to two groups, one of which was offered greater
      involvement in care. Of the participants in the experimental group, the four who
      accepted this opportunity all had relatives admitted in the past 6 months. After
      6 weeks there was no significant difference between the groups. Trends suggest
      that similar programs may be most useful in the early months following admission,
      while care-givers are in the process of adapting to their new circumstances. It
      appears that nursing staff must be sensitive to the different needs for
      involvement in the care of relatives.

PMID- 9265550
TI  - Let's get critical: a personal reflection on an encounter with the politics of
      difference at an international conference.

PMID- 9265551
TI  - A bush nurse's life.

PMID- 9265552
TI  - Potential novel roles of luteinizing hormone and human chorionic gonadotropin
      during early pregnancy in women.

PMID- 9265553
TI  - Effect of excessive GnRH-binding substance on circulating maternal hCG in human
      pregnancy.
AB  - Gonadotropin-releasing hormone (GnRH) can stimulate the release of placental
      human chorionic gonadotropin (hCG). Thus, at the onset of these studies it was
      the objective to define the relationship of hCG to GnRH in the maternal
      circulation throughout pregnancy, focusing on early pregnancy. Blood samples were
      collected at 8, 10, 12, 14, 16, 28 and 36 weeks of gestation during labor and the
      GnRH and hCG levels were determined by radioimmunoassay. Of 39 pregnancies, a
      GnRH-binding substance was found in the maternal circulation of three. This GnRH
      binding substance resulted in erroneous GnRH levels, due to the very high non
      specific binding. In the pregnant women without this GnRH-binding substance, GnRH
      attained highest concentrations at 12-14 weeks. The typical peak of hCG at 8-10
      weeks of gestation was observed in this group, while the group of patients having
      the GnRH-binding substance had significantly lower hCG levels. Each of the
      patients with circulating GnRH-binding substance had prior pregnancy(s) and two
      of the three had a prior pregnancy loss. The nature of this GnRH-binding
      substance was investigated using gel chromatography. After incubation of
      [125I]GnRH with patient plasma for 3 days this substance was shown to be of high
      molecular weight which was ethanol precipitable. This binding substance may
      therefore be an antibody, since it appears to be a high molecular weight protein
      requiring a number of days to bind the [125I] GnRH. This GnRH-binding substance
      may be of physiological importance, since the circulating hCG level was
      significantly less in the group of patients with this substance than in those
      without.

PMID- 9265554
TI  - Phenotypic comparison of natural killer cells from peripheral blood and from
      early pregnancy decidua.
AB  - In this descriptive flow cytometric study we analyzed the phenotype of human
      large granular lymphocytes from the decidua (DLGL) of first-trimester pregnancy.
      Expression of CD56 at high density on DLGL suggests a relationship to the small
      CD56bright+ subpopulation of peripheral blood natural killer (PBNK) cells. In
      comparison, these cell types differ in respect to the expression of a variety of
      adhesion molecules and receptors implicated in homing, migration and activation.
      In contrast to CD56bright+ PBNK cells, DLGL were still brighter for CD56 and show
      higher expression for CD29 and CD45RO. Less expression was found for CD15s, CD43,
      CD44, CD45RA, CD62L and HLA-DR. CD11a to c and CD18 were distributed in bimodal
      form on DLGL, part of the cells being negative. In summary, we found considerable
      differences between the cell surface marker profiles of DLGL and PBNK cells
      (subpopulations of the latter being separately analyzed).

PMID- 9265555
TI  - Termination of early pregnancy in the rat by a single dose of human menopausal
      gonadotropin.
AB  - Human menopausal gonadotropin (hMG) is commonly used to induce ovarian follicular
      development and ovulation in infertile women. This report is a preliminary
      analysis of the ability of hMG to cause folliculogenesis and ovulation in
      pregnant laboratory animals. Wistar rats were injected subcutaneously with 0.5 mg
      of hMG on selected days of pregnancy. In addition, 2 days after receiving hMG,
      one group of animals was injected with 50 IU of human chorionic gonadotropin
      (hCG) as a substitute for an ovulation-inducing dose of luteinizing hormone. A
      single dose of hMG caused follicular development and ovulation in the pregnant
      animals. Furthermore, the results show that such hormone treatment usually
      terminated the gravid state of the animals. The frequency of pregnancy
      termination was greater (1) When hMG was administered during the first quarter of
      the 21-day gestation period; (2) When higher doses of hMG were used; and (3) When
      the hMG injection was followed 2 days later by hCG. In conclusion, hMG can
      terminate early pregnancy in a laboratory animal like the rat, and this
      observation raises the possibility that it may also act as an abortifacient agent
      in humans. Therefore, a more extensive analysis of the effects of hMG on
      pregnancy is warranted.

PMID- 9265556
TI  - In vivo evidence for the existence of a threshold for hyperglycemia-induced major
      fetal malformations: relevance to the etiology of diabetic teratogenesis.
AB  - The present study was carried out to evaluate whether hyperglycemia-induced major
      fetal anomalies are thresholded phenomena. Streptozotocin (STZ)-treated female
      ICR mice were examined on day 19 of pregnancy by methods routinely used in
      Segment II teratological studies. Simultaneously, the glucose and hemoglobin A1c
      (HbA1c) levels in maternal-blood were measured and mice with glucose levels > 9.5
      mmol/l (mean + 3 SD) were considered to be diabetic. The occurrence of litters
      with fetuses having gross structural anomalies was clearly associated with
      glucose levels > 27.8 mmol/l. A wide range of HbA1c levels (between 6 and 18 SD
      above the mean) were observed, within which only single malformed fetuses were
      found in the litters of diabetic females. A decreased pregnancy rate in diabetic
      ICR mice was associated with glucose levels > 16.7 mmol/l and with HBA1c levels >
      6 SD above the mean. The results of this study suggest that there is a threshold
      glucose level associated with a clear increase of the number of litters with
      severely malformed fetuses in diabetic ICR mice. Results of this study also
      suggest the existence of HbA1c-associated factors determining, along with
      glucose, the teratogenic response of ICR mice to diabetes. The interpretation of
      results obtained in terms of the multifactorial/threshold model leads to the
      hypothesis that the teratogenic potential of diabetes may consist of two
      components; one associated with 'direct' teratogens perturbing developmental
      processes in embryos at a 'critical moment' in organogenesis, and a second
      component, associated with a direct or indirect influence of the diabetic
      environment on developmental processes in the preimplantation embryos.

PMID- 9265557
TI  - Influence of nicotine on progesterone and estradiol production of cultured human
      granulosa cells.
AB  - The purpose of this study was to investigate the direct action of one of the main
      constituents of cigarette smoke on corpus luteum function. Progesterone and
      estradiol production were measured in the presence and absence of nicotine as
      free base or bitartrate salt with or without luteinizing hormone (LH) stimulation
      using radioimmunoassay in an in vitro granulosa cell culture system. Human
      granulosa cells were obtained from 19 patients undergoing in vitro fertilization
      embryo transfer treatment for infertility at the University Women's Hospital,
      Tubinge, Germany. Nicotine free base augmented estradiol secretion and inhibited
      progesterone secretion by human granulosa cells in a dose-dependent manner.
      Nicotine bitartrate had little effect on steroid secretion. If granulosa cells
      were stimulated with LH, both nicotine preparations suppressed estradiol
      secretion, however, only nicotine bitartrate additionally inhibited progesterone
      secretion. The results suggest that cigarette smoking specifically affects the
      control mechanisms of intraovarian processes which are responsible for normal
      luteal function.

PMID- 9265558
TI  - Current progress in early pregnancy investigation.

PMID- 9265559
TI  - Endothelin in the pulmonary circulation with special reference to hypoxic
      pulmonary vasoconstriction.
AB  - 1. The experimental model using periods of ventilation with a gas mixture
      containing 10% oxygen in the anesthetized pig was found to induce HPV that was
      reproducible and remained stable for up to two hours. 2. Intrapulmonary infusion
      of ET-1 during normoxia resulted in a dose-dependent increase in the SVR with a
      concomitant decrease in CO and rise in PVR. Infusion of ET-3 and S6c evoked
      similar responses, but of a considerably smaller magnitude. The dose-dependent
      systemic vasoconstriction evoked by ET-1 infusion was reduced after
      administration of the combined ETA and ETB receptor antagonist bosentan as well
      as the selective ETA receptor blockers BMS-182874 and TBC-11251 indicating that
      this effect is primarily mediated by ETA receptors. ETA receptors are present in
      porcine pulmonary arteries, since BMS-182874 caused a rightward shift of the
      concentration-response curve to ET-1 in vitro. 3. Administration of selective ETA
      or combined ETA and ETB antagonists but not of a selective ETB antagonist
      reduced the SVR in normoxic pigs, indicating that ET acting through ETA receptors
      contributes to systemic vascular tone in the pig. In addition, ETA selective and
      non-selective ETA and ETB antagonists produced a reduction of PVR, although this
      effect was less consistent than the influence on SVR. This indicates that ETA
      receptors may contribute to basal pulmonary vascular tone. The plasma levels of
      ET-1 increased following the non-selective ET receptor antagonist bosentan but
      were unaffected by selective ETA receptor antagonism. 4. Intrapulmonary infusion
      of ET-1 produced in low doses a pulmonary vasodilatation during HPV in the pig.
      This pulmonary vasodilatory effect was also evident when ET-3 or S6c was infused.
      The pulmonary vasodilatory effect of ET-1 infusion was abolished following
      administration of the selective ETB receptor antagonist BQ-788, indicating that
      the pulmonary vasodilatory effect of ET in HPV in the pig is mediated by ETB
      receptors. Higher doses of ET-1 infusion during HPV resulted in systemic and
      pulmonary vasoconstriction. 5. Both combined ETA and ETB blockade using bosentan
      and selective ETA receptor inhibition using BMS-182874 or TBC-11251 reduced the
      development of HPV in the pig. In addition, bolus injection of TBC-11251 reversed
      already established HPV. Selective ETB receptor antagonism had no effect on HPV.
      These findings suggest that ETA receptor activation contributes to HPV in the
      pig. 6. The concentration-dependent contraction evoked by ET-1 in human vessels
      in vitro (LAD, IMA, PA, SV) was reduced after incubation with BQ-123 and
      bosentan. Inhibition of NO- and prostaglandin-synthesis enhanced the contractions
      in the LAD and IMA, but not in the PA and SV. These findings are in concord with
      a predominance of ETA receptors in the investigated vessels. Nitric oxide and
      prostacyclin seem to be important determinants of the functional response to ET
      in human LAD and IMA, but of less importance in the PA and SV. 7. In the human
      vessels investigated, the tissue content of ET-1 was higher than that of ET-3 and
      resembled the distribution of the perivascular C-fiber peptide CGRP. Tissue
      content of ET-1 was considerably lower than that of sympathetically stored NPY.
      In human plasma, the arterial and venous concentration of ET-1 was higher in
      patients with chronic hypoxemia and borderline hypertension than in the venous
      samples drawn from healthy subjects. The arterial and venous levels of ET-1 did
      not differ significantly either at rest or during ET-1 infusion, indicating that
      the pulmonary circulation does not extract ET-1 in these patients. 8. The study
      in patients with borderline pulmonary hypertension and chronic hypoxaemia showed
      no pulmonary vasodilatory effects of intrapulmonary ET-1 infusion but rather
      systemic vasoconstriction and decreased CO. The AVO2 difference increased
      markedly during ET-1 infusion. 9. (ABSTRACT TRUNCATED)

PMID- 9265560
TI  - Challenges for medical informatics in the 21st century.
AB  - This paper introduces the topic of this special issue: challenges for medical
      informatics in the 21st century. This paper discusses the nature of medical
      informatics. Some descriptions and definitions of medical informatics are
      reviewed. Then the research aspects of medical informatics are discussed. It is
      argued that the more mundane aspects of medical informatics like system
      development and implementation are important and need further consideration,
      especially concerning social aspects and correctness.

PMID- 9265562
TI  - Critical dimensions in medical informatics.
AB  - A typology of medical informatics applications is proposed around three
      dimensions: the dimension of care, the dimension of information and knowledge,
      and the aspects of the computerized society. These dimension can help both to
      evaluate application or research papers in the field or to derive long term goals
      for the discipline. In the first dimension medical informatics appears more as a
      technology driven by external forces such as the general progress of medicine or
      the integration of economical constraints in the choice of optimal procedures. It
      is argued that barriers to overcome as well as challenges for future research
      mainly remain in the two last dimensions.

PMID- 9265561
TI  - Aims and tasks of medical informatics.
AB  - Ten major long-term aims and tasks, so to speak 'grand challenges', for research
      in the field of medical informatics, including health informatics, are proposed
      and described. These are the further development of methods and tools of
      information processing for: (1) diagnostics ('the visible body'); (2) therapy
      ('medical intervention with as little strain on the patient as possible'); (3)
      therapy simulation; (4) early-recognition and prevention; (5) compensating
      physical handicaps; (6) health consulting ('the informed patient'); (7) health
      reporting; (8) health care information systems; (9) medical documentation and
      (10) comprehensive documentation of medical knowledge and knowledge-based
      decision support. Work is, in part, already in progress. To all these aims and
      tasks medical informatics can and may be should make substantial contributions.
      Prior to outlining the above aims and tasks, an account is given of the meaning
      of medical informatics, of the objective it pursues in general and of its
      achievements so far. The present paper intends to contribute to a broad public
      discussion of the aims and tasks for research in the field of medical
      informatics.

PMID- 9265563
TI  - Grand challenges in health informatics. An information systems perspective
      commentary on Haux.

PMID- 9265564
TI  - A changing world of grand challenges.

PMID- 9265565
TI  - A look at nursing informatics.
AB  - This is a companion article to the article on Medical Informatics. It focuses on
      the new nursing specialty-Nursing Informatics. This article provides an overview,
      scope, definitions, data standards, goals, and research initiatives designed to
      advance the status Nursing Informatics. Seven research priorities have been
      proposed which not only provides the direction for Nursing Informatics research,
      but also the focus for computer-based nursing information systems.

PMID- 9265566
TI  - The internal challenges of medical informatics.
AB  - Haux's [7] basic assumption that the object of medical informatics is: "... to
      assure and to improve the quality of healthcare as well as the quality of
      research and education in medicine and in the health sciences ..." is taken as a
      starting point to discuss the three main topics: What is the meaning of medical
      informatics (i.e. what should be the main activities of medical informatics to
      bring maximum benefit to medicine)? What are the achievements and failures of
      medical informatics today (again considering the impact on the quality of
      healthcare)? What are the main challenges? Concerning the definition of medical
      informatics it is argued that one should not hide the link to basic informatics
      and, for that matter to computers, completely behind abstract definitions. After
      an analysis of the purposes of the definition of a discipline, a differentiated
      definition of the scope of medical informatics, rather general when concerning
      the field of scientific interest, more focused when concerning the practical
      (constructive) applications, is proposed. Contrasting Haux's chapter on
      achievements of medical informatics we concentrate on and analyse non fulfilled
      promises of medical informatics to derive lessons for the future and to propose
      'generic' (or core) tasks of medical informatics to meet the challenges of the
      future. A set of 'internal challenges' of medical informatics to change
      priorities and attitudes within the discipline is put forward to enable medical
      informatics to meet the 'external challenges' listed by Haux.

PMID- 9265567
TI  - On the medical informatics structure.
AB  - This paper contributes to the discussion of R. Haux paper on essential aims and
      tasks of medical informatics. New views on structure of informatics and
      consequently medical informatics are given. Information is introduced as outside
      and inside information. Inside information is divided into three different types
      as data, evidence and knowledge. This terminology slightly differs from the
      commonly used terminology data, information and knowledge. Based on understanding
      of information as outside and inside information the field of informatics is
      divided into four rings, namely Information Basic Ring, Information Methodology
      Ring, Information Interface Ring and Information Technology Ring. Medical
      informatics is defined and its structure explained using four information rings.
      These views on informatics and medical informatics open possibilities to see more
      clearly where are the essential aims and tasks of medical informatics.

PMID- 9265569
TI  - Italian gastroenterology: present and future.

PMID- 9265568
TI  - Medical informatics in the heart of health care.

PMID- 9265570
TI  - Helicobacter and liver disease.

PMID- 9265571
TI  - HIV-related diarrhoea: where do we stand?

PMID- 9265572
TI  - Chronic atrophic gastritis and Helicobacter pylori infection in primary biliary
      cirrhosis: a cross-sectional study with matching.
AB  - BACKGROUND/AIMS: Primary biliary cirrhosis (PBC) is a chronic liver disease
      characterized by exocrine gland impairment. Up to now there have been no reports
      dealing with gastric mucosa involvement in this autoimmune condition, which is
      frequently associated with Sjogren's syndrome. The aim of this study was to
      investigate the morphologic, biochemical and immunological features of the
      gastric mucosa in PBC. METHODS: A cross-sectional study with matching was
      performed. Thirty-three PBC patients (30 F, 3 M, mean age 58 years; 17 with stage
      II-III, and 16 with stage IV disease) and 33 sex- and age-matched dyspeptic
      controls were included. Six biopsy specimens from the fundus (2), body (2) and
      antrum (2) were taken from all patients and controls. A serological assessment
      was performed for each subject, i.e. pepsinogen A (PGA), pepsinogen C (PGC),
      gastrin (G), and antibodies against Helicobacter pylori (anti-Hp IgG). RESULTS:
      Endoscopic gastritis was found in 22 PBC patients (66.6%). There was no
      difference between PBC patients and controls regarding the percentage of subjects
      with mild, moderate, severe or atrophic gastritis (AG). There was no difference
      in gastric mucosal involvement between PBC subjects with or without secondary
      Sjogren's syndrome. A discrepancy was observed in the data obtained with respect
      to Helicobacter pylori (H. pylori) infection. H. pylori colonization was
      significantly more frequent in controls than in PBC patients (79% vs 49%, p <
      0.002), but anti-Hp IgG were detected in the same percentage in the two groups
      (90% vs 83% respectively). There was no difference between the two groups in the
      PGA, PGC, PGA/PGC ratio, or gastrin. Eight PBC patients had esophageal varices.
      CONCLUSIONS: PBC patients are not characterized by chronic atrophic gastritis.
      Even though they present chronic gastritis with the same prevalence as dyspeptic
      controls, and show signs of previous H. pylori infection as frequently as
      dyspeptic patients, they are actually much less frequently infected. The reasons
      for this observation are unclear.

PMID- 9265573
TI  - Organ-specific autoantibodies in coeliac disease: do they represent an
      epiphenomenon or the expression of associated autoimmune disorders?
AB  - BACKGROUND AND AIMS: The occurrence of autoimmune disorders and organ-specific
      autoantibodies has been reported in coeliac disease. We assessed the prevalence
      of organ-specific autoantibodies in coeliac patients and evaluated whether their
      finding is an expression of associated autoimmune diseases. METHODS: Sera from 70
      coeliac disease patients were tested for thyroid microsomal, gastric parietal
      cell, adrenal cortex and pancreatic islet cell antibodies by indirect
      immunofluorescence on O blood group human tissues. RESULTS: Eighteen coeliacs
      (26%) were positive for at least one of the autoantibodies studied; thyroid
      microsomal antibodies showed a higher prevalence (21%) than parietal cell (11%),
      adrenal cortex (4%) and islet cell antibodies (3%). In 15 (21%) of the 70
      coeliacs studied an association with autoimmune diseases was found, including
      insulin dependent diabetes mellitus (6 cases), autoimmune hepatitis (3 cases),
      hypothyroidism (4 cases), thyrotoxicosis (1 case) and dermatomyositis (1 case).
      One or more organ-specific autoantibodies were positive in 12 (80%) of the 15
      coeliacs with autoimmune disorders in comparison with their positivity in 6 (11%)
      of the 55 coeliacs without autoimmune diseases (p < 0.0001). CONCLUSIONS: The
      finding of organ-specific autoantibodies in coeliac patients discloses the
      coexistence of a wide spectrum of immunological diseases.

PMID- 9265574
TI  - Antibiotic and cholestyramine treatment of chronic diarrhea in HIV-infected
      children.
AB  - BACKGROUND: Chronic diarrhea is a common feature in children infected with human
      immunodeficiency virus (HIV), and is associated with an increased risk of death
      in these patients. To describe the effects of an empiric treatment on diarrhea
      and body weight on HIV-infected pediatric patients. PATIENTS: Eleven vertically
      HIV-infected children with chronic diarrhea were treated with oral gentamicin,
      metronidazole and cholestyramine for 3 to 5 days. RESULTS: In children not
      infected by Cryptosporidium the treatment resulted in a 50% reduction of stool
      frequency and a 9% increase in body weight. No statistically significant effect
      was found in children harbouring this parasite. Diarrhea relapsed within 1-2
      months in 3/3 children with Cryptosporidium and in 1/8 children without
      Cryptosporidium (p < 0.05). No untoward side effects from the treatment were
      observed. CONCLUSIONS: These results suggest that an empiric treatment of this
      type should be attempted early in HIV-infected children with chronic diarrhea,
      particularly in those not infected by Cryptosporidium.

PMID- 9265575
TI  - Morphological injury of the intestinal mucosa and infection in patients with
      AIDS. The role of combined tissue and stool examination.
AB  - AIMS: To define the relationship between morphological injury of the intestinal
      mucosa and infections in AIDS patients. METHODS: Forty-nine AIDS patients were
      examined by upper gastrointestinal (GI) endoscopy and 8 of them also by lower GI
      endoscopy. Biopsy specimens, taken from the lower duodenum, esophagus and rectum,
      were studied by light (L.M.) and transmission electron microscopy (T.E.M.). Stool
      examination for microorganisms was routinely performed in all patients. RESULTS:
      Microorganisms were detected in 37 of the 49 patients (75.5%) by combined tissue
      and stool examination. The histological study revealed villous atrophy, inter-
      and intra-enterocyte oedema and epithelial degenerative changes in most of the
      patients whether or not they had detectable microorganisms. CONCLUSIONS: Combined
      methods (endoscopy, L.M. and T.E.M., studies of tissue samples, microbiological
      study of stool samples) may be used to improve the documentation of infections
      and morphological injury of the intestinal mucosa in AIDS patients.

PMID- 9265576
TI  - Histological changes but not virus eradication reflect biochemical improvement in
      chronic hepatitis C patients showing a long-term response to interferon alpha
      therapy.
AB  - AIMS: To assess the relationship between changes in liver histology and
      virological parameters of HCV infection in patients with a sustained biochemical
      response to alpha-interferon treatment for chronic hepatitis, with the aim of
      identifying the most reliable indicator of treatment efficacy. METHODS:
      Quantitative serial testing of HCV-RNA in plasma samples collected on a monthly
      basis over the last period of post-treatment follow-up were tested in sixteen
      subjects with > or = 12 months aminotransferase normalisation following
      discontinuation of interferon therapy. The quantitative HCV-RNA determination in
      plasma was performed by a competitive reverse-transcription polymerase-chain
      reaction. Pretreatment and 12-month post-treatment liver histologies were blindly
      evaluated using a semi-quantitative scoring system. At these times a qualitative
      HCV-RNA analysis was also carried out. RESULTS: The post-treatment histological
      grading score was significantly reduced. Nevertheless, all patients except one
      tested positive for HCV-RNA in plasma (mean 1.7 x 10(6) molecules/ml): nine were
      positive in all the serial determinations, while the remaining 6 were
      intermittently positive. No relationship between genotype, viral load, pattern of
      viremia (intermittent or continuous) and change in histological score was found.
      CONCLUSIONS: Changes in liver histology are the most reliable indicator of the
      efficacy of interferon treatment in hepatitis C related liver disease. HCV-RNA
      clearance based on serial sampling does not appear to be a reliable indicator,
      even in the presence of a sustained biochemical response and histological
      improvement.

PMID- 9265578
TI  - Low rate of HCV transmission from women infected with contaminated anti-D
      immunoglobulin to their family contacts.
AB  - PURPOSE: To analyse the spread of HCV infection from women infected with batch
      number proven contaminated anti-D immunoglobulin to their family contacts.
      PATIENTS AND METHODS: Index cases. Sixty women who had been infected with
      hepatitis C after receiving HCV contaminated anti-D Immunoglobulin. All were
      positive for HCV antibodies by ELISA (Ortho & Murex, Abbott Laboratories) and
      RIBA3 (Chiron Corporation, Emerville, California) and were viraemic by PCR for
      HCV-RNA (Roche Diagnostic Systems, Basel, Switzerland). Liver biopsies were
      performed in 45 patients. All were in stable longterm relationships. CONTACTS:
      Fifty-five partners and 170 children were tested for HCV antibodies by ELISA
      (Ortho, Murex). Any positive contact was also tested for antibody by RIBA-3, HCV
      RNA by PCR, genotype determined and also had a liver biopsy performed. RESULTS:
      No male partners and only one child tested positive for HCV antibodies indicating
      low exposure over a combined time period of 862 years for partners and 2465 years
      for children. CONCLUSIONS: This study suggests a zero female to male sexual
      transmission rate of HCV and a low vertical transmission rate in anti-D
      associated HCV infection.

PMID- 9265577
TI  - Prognostic factors for long-term survival in cirrhotic patients after the first
      episode of liver decompensation.
AB  - BACKGROUND/AIMS: Prognostic studies on cirrhosis are needed, since several
      attempts to obtain better survival predictors than the empirically derived Child
      Pugh's score have failed. METHODS: Four hundred and ninety-four consecutive in
      patients with cirrhosis at the first episode of decompensation (ascites,
      jaundice, encephalopathy) and/or of digestive haemorrhage from ruptured
      oesophageal varices were followed from admission (1983-1989) to 1993, studying
      the relationship between 26 prognostic variables and survival. Three prognostic
      models were constructed using Cox's regression model and the Receiver Operating
      Characteristic (ROC) analysis was used to compare their predictive ability.
      RESULTS: During follow-up 351 patients died (median cumulative survival 1.82
      years). Child-Pugh's score (explicative variable of the first Cox's model),
      albumin and encephalopathy among the 5 Child-Pugh variables (second model), and
      oesophageal varices haemorrhage and 3 biochemical indexes among the 7 significant
      variables on univariate analysis (third model) correlated with survival. The area
      under the ROC curve of the first model did not significantly differ from that for
      the other 2 models. CONCLUSIONS: The Child-Pugh's score is still the best and
      simplest index for assessing the prognosis of liver cirrhosis.

PMID- 9265579
TI  - Eosinophilic ileocolitis by Enterobius vermicularis: a description of two rare
      cases.
AB  - BACKGROUND: Human enterobiasis is usually mild. Occasionally, however, an
      "ectopic" disease may occur with a more severe course. Two rare cases of
      eosinophilic ileocolitis due to Enterobius vermicularis infection are reported
      here. CASE REPORTS: Case n degree 1 was 46 years old, presenting with fever and
      bloody diarrhoea. Blood eosinophilia was present. Stool microscopy demonstrated
      red blood cells and leukocytes. A 2 mm long worm with bilateral cervical wings
      was found in wet-mount preparations of faecal samples. The Scotch tape test was
      positive for Enterobius vermicularis eggs. Colon biopsy specimens showed massive
      eosinophilic infiltration and a typical pinworm section overlying the infiltrated
      mucosa. Case n degree 2 was a 24-year-old, anti-HIV negative homosexual,
      presenting with watery diarrhoea. Tests for malabsorption were negative. Three mm
      long adult male E. vermicularis were found on stool microscopy. Biopsy specimens
      from the colon showed eosinophilic infiltration. In both cases a 200 mg/day
      course of oral mebendazole eliminated the symptoms within 3 days. CONCLUSIONS: In
      these two cases the clinical presentation of enterobiasis was atypical. A common
      finding was the eosinophilic infiltration of bowel mucosa, although it is still
      uncertain whether the worm per se may induce mast cell degranulation and
      eosinophil activation. Nevertheless, the possibility of Enterobius vermicularis
      infection should be considered in the presence of eosinophilic ileocolitis.

PMID- 9265580
TI  - Macrocystic serous cystadenoma of the pancreas. Diagnostic, therapeutic and
      pathological considerations of three cases.
AB  - BACKGROUND: Macrocystic serous cystadenoma (MSC) of the pancreas is a new entity
      that has recently been well recognised. This tumour is quite similar in aspect to
      the mucinous cystic tumours (MCT) but its prognosis is much better, so that a
      correct diagnosis before surgery is important. PATIENTS: Three patients
      undergoing surgery in the 1st Surgical Clinic of the University of Bologna for
      suspected cystic lesions were found to have macrocystic serous cystadenoma (MSC)
      of the pancreas. In two cases a biopsy was performed during surgery, but in only
      one was a correct diagnosis of MSC made; in the other the diagnosis was
      lymphangioma. In the remaining case a biopsy was not performed because the high
      19/9 CA level in the blood suggested a diagnosis of MCT of the pancreas. In all 3
      cases the tumour was successfully removed by surgery. CONCLUSIONS: Macrocystic
      serous cystadenoma (MSC) of the pancreas represents a variant of the serous
      cystic tumors, which encompass microcystic adenoma and serous cystadenocarcinoma.
      MSC must be distinguished from MCT because it exhibits a different biological
      pattern and requires a different surgical approach. Therefore, we would underline
      the importance of a biopsy in making the differential diagnosis.

PMID- 9265581
TI  - Endoscopic retrieval of a surgical gauze from the common bile duct.
AB  - Non-parasitic foreign bodies in the common bile duct are rare and usually require
      laparotomy. We report the successful removal by endoscopy of a surgical gauze
      seven years after a simple cholecystectomy. The foreign body had been
      cholangiographically misdiagnosed as a large stone. The possibility of a foreign
      body that has migrated into the common bile duct should be considered in patients
      with cholangitis. Endoscopic sphincterotomy is the procedure of choice, though
      other extraction techniques may occasionally be necessary.

PMID- 9265582
TI  - Peptic ulcer in patients with liver cirrhosis: a retrospective endoscopic and
      clinical study.
AB  - AIM: It has been showed that peptic ulcer is more frequent in patients with liver
      cirrhosis, is associated with the severity of cirrhosis, and occurs without upper
      abdominal pain in up to 70% of patients and with complications in 29%. The aim of
      this study was to retrospectively assess the characteristics of peptic ulcer in a
      large series of patients with liver cirrhosis. MATERIALS AND METHODS: In this
      retrospective study the consecutive records of 1,748 endoscopies, performed in
      patients with liver cirrhosis during a period of 14 years, were reviewed to
      evaluate the frequency and clinical characteristics of peptic ulcer. RESULTS: The
      ulcer prevalence was 6.3%, and 77.5% of the ulcers were asymptomatic.
      Complications from ulcer were present in 29% of all patients and in 32% of those
      who has the first diagnosis of ulcer during the study. Patients with asymptomatic
      ulcer had a more decompensated cirrhosis. After healing, 20%-25% of the recurrent
      ulcers had complications while patients were on standard maintenance treatment.
      CONCLUSIONS: This retrospective study confirms the high frequency of peptic ulcer
      in patients with liver cirrhosis. It also confirms that the peptic ulcer in these
      patients is very often asymptomatic and associated with concurrent complications,
      especially in those with more severe liver disease. The complication rate in
      recurrent ulcers was 20%-25%. However, due to the retrospective nature of this
      study, after ulcer healing the endoscopic follow-up was irregular. Regularly
      repeated endoscopy should be carried out in patients with liver cirrhosis and
      peptic ulcer to diagnose new and recurrent ulcers and to prevent related
      complications.

PMID- 9265583
TI  - Moving towards the optimal treatment of chronic hepatitis C.
AB  - Almost 10 years after the first report of the effectiveness of interferon (IFN)
      for chronic NANB hepatitis, the optimal treatment for chronic hepatitis C is
      still a matter of debate. The issue of the relative importance of higher doses
      versus a longer period of therapy remains unsettled, since the long-term response
      may be a function of the total dose received. Controlled studies have shown that
      high doses of IFN (5-6 MU t.i.w.), a long period of therapy (> 12 months) and the
      administration of a large total dose are all associated with a higher cure rate.
      However, these measures can cause more adverse effects and certainly cost more
      than the current schedule of 3 MU t.i.w. for a period of 6 months. The standard
      schedule may be appropriate for subjects with pre-treatment features predictive
      of a good response (non-Ib genotype, low viraemia, absence of cirrhosis).
      Alternative treatment schedules or combination therapy with interferon/ribavirin
      should be considered in subjects with normalized alanine aminotransferase (ALT)
      levels, but who are still viremic after three months of therapy, as well as in
      relapsers and in non-responders.

PMID- 9265584
TI  - Alcoholic liver cirrhosis after the advent of hepatitis C virus: some reflections
      on its epidemiology and on the concept of attributable risk. Collaborative GESIA
      and AISF Groups. Gruppo Epidemiologico della Societa Italiana di Alcologia and
      Associazione Italiana per lo Studio del Fegato.
AB  - The recent availability of hepatitis C virus (HCV) infection markers has led to
      the hypothesis that the prevalence of alcoholic liver cirrhosis (ALC) may be far
      lower than has hitherto been believed. On the other hand difficulties in
      obtaining a reliable patient history of alcohol consumption and of making a
      differential diagnosis on the basis of histology suggest that the aetiology role
      of alcohol may be underestimated. Furthermore, epidemiological data strongly
      suggest that an individual susceptibility of alcoholic liver damage exists. The
      interaction between alcohol consumption and acquired factors, in particular
      hepatitis B and C viruses and nutrition, can be studied using an epidemiological
      approach. The concept of attributable risk, which depends on the strength of the
      aetiological factors and on their diffusion in the target population, is helpful
      in this context. Preliminary estimates suggest that alcohol is at least as
      important as HCV infection in causing liver cirrhosis in Italy. A nationwide
      study (SIDE-CIR Project) is currently being conducted in order to clarify this
      issue.

PMID- 9265585
TI  - Acid secretion, serum pepsinogen A and Helicobacter pylori.

PMID- 9265586
TI  - A severe case of Yersinia enterocolitica infection in a thalassemic patient.

PMID- 9265603
TI  - Excellence in practice requires commitment and involvement but it also requires
      power in practice.

PMID- 9265604
TI  - Critical social theory as a grounded process.
AB  - This article reflects upon the research process that uses critical social science
      as its basis. Some of the common criticisms of critical social science research
      are rebutted by following the research trail taken by the authors when
      undertaking their own projects. The similarities and differences of critical
      social science and the interpretative methodologies are outlined in the selection
      of study area, the relationship of the researcher and participants, ethical
      issues, and data collection and analysis. The writers conclude that critical
      social science research reports that are correctly carried out should be firmly
      grounded in each of these stages, thereby a foundation for nursing and midwifery
      practice.

PMID- 9265605
TI  - The triage role in emergency nursing: development of an educational programme.
AB  - This study explores the professional and educational development of emergency
      nurses and their beliefs regarding the appropriate content for a triage
      educational programme. A descriptive survey was conducted of emergency nurses
      employed by randomly selected teaching and non-teaching hospitals. Data analysis
      showed that emergency nurses used various methods to prepare and maintain their
      triage expertise. The survey found that the best method to prepare the novice
      emergency nurse for the triage role was to use a combination of a triage
      educational programme and clinical experience. Respondents indicated great
      interest in enrolling in an educational programme and, as a result of this
      survey, a comprehensive triage educational programme has been developed.

PMID- 9265606
TI  - Quality of elderly-patient care: an interrupted time series study.
AB  - This study is part of a project that aimed to increase the participation of
      informal caregivers in the hospital care for elderly patients. The staff who
      worked in the wards that were studied created activity programmes for caregivers
      and changed their ward policies to encourage the participation of the caregivers.
      In addition, quality assurance programmes were developed and primary nursing was
      introduced to ensure individualized, need-based and family centered care. In
      order to explore the changes in perceived quality of care, and to test the
      differences in care quality between the study and the control wards (i.e. two
      wards in a university hospital, two wards in a geriatric unit and two wards of a
      nursing home), the interrupted time series with a non-equivalent control group
      time series design was used. During periods of 2 months in 1991, 1992 and 1993
      the data were collected from elderly patients (n = 97) and their informal
      caregivers (n = 369) using a structured questionnaire based on need theories. The
      results indicated that the quality of care was improved, especially in the study
      wards of the university hospital and of the nursing home. This care quality
      measure was found to be a useful tool for getting feedback from patients and
      their caregivers concerning care given. Aspects of nursing practice that needed
      to be improved were identified (i.e. poor communication between the patient,
      their caregiver and staff, and lack of support to the patient and caregiver by
      staff).

PMID- 9265607
TI  - Power in partnership.
AB  - This paper focuses on the meaning and process of collaboration, particularly in
      the area of research and clinical practice. Much has been written about the
      existing gaps between research and the practice of nursing; however, action
      research is one mechanism that allows these elements to be drawn together.
      Research developed through collaborative participation has the potential to
      harness the energy, enthusiasm and talents of nurses at different levels and
      practice into a cohesive group motivated to achieve professional development and
      quality practice goals. Action research that is built on the philosophy of a
      quality within the process and significance of the group can lead to effective
      practice in nursing. Power can be found in partnership.

PMID- 9265608
TI  - The need to develop nursing practice through innovation and practice change.
AB  - This paper examines some of the strategies that can be used to produce change in
      nursing. These strategies range from the power-coercive through rational
      empirical to the normative-re-educative. Strategies that promote a 'bottom-up'
      approach are advocated for clinical nursing and some of the principal factors
      towards success, such as team building, the presence of a clinical leader and
      planning are indicated. The paper will also expand on what needs to be changed in
      nursing, and what the purpose of such changes are. It is argued that externally
      focused efforts of change, such as the organization of care or new practices are
      only part of the picture. The journey of change also requires an inner
      exploration of who we are and what are we seeking to achieve in nursing.

PMID- 9265609
TI  - Group interviewing for the purpose of selection.
AB  - This paper describes the process of utilizing group interview techniques combined
      with elements of qualitative methodology to facilitate the selection of newly
      registered nurses for acceptance into a graduate nurse programme. The paper
      demonstrates the flexibility and adaptability of group interviewing large numbers
      of candidates for a limited number of positions. It explores the process from a
      humanistic perspective and identifies the strengths and weaknesses of the
      instrument, which will enable further refinement and applicability.

PMID- 9265610
TI  - The mirror as a therapeutic tool for patients with dementia.
AB  - The aim of the study was to examine changes in patient behavior that occurred as
      a consequence of looking in a mirror. How do dementia patients relate to their
      image in the mirror? Is the use of the mirror effective in raising levels of self
      awareness, calmness and satisfaction? The survey was carried out on 100 patients
      suffering from dementia: 67 women and 33 men aged between 67 and 85. The findings
      showed that most responses to looking in the mirror were positive and raised the
      patients' awareness regarding self-care. In a small number of patients, looking
      into the mirror aroused feelings of anger or despair, followed by relief and
      calmness. Findings indicated that the use of mirrors enabled nurses and
      caregivers to communicate better with patients. Most patients appeared to benefit
      in various ways from looking into the mirrors. The staff felt that use of mirrors
      was an inexpensive and efficient therapeutic tool for improving care of demented
      aged patients.

PMID- 9265611
TI  - Relaxation: with or without imagery?
AB  - Although the benefits of relaxation are widely recognized, clinicians need to
      remain cognizant of its possible adverse effects. Equally, some people with
      mental illness may experience an exacerbation of their symptoms with the
      injudicious use of relaxation techniques that use imagery. This paper explores
      two conditions where vivid, often emotionally charged, images are problematic:
      (i) post traumatic stress disorder; and (ii) hallucinoses. Individuals who have
      these disorders may have difficulty controlling shifts between these internal and
      external events, or difficulty even recognising events as internal rather than
      external. Employing a relaxation technique that encourages imagery is likely to
      produce a stronger reaction because the impact of the imagery is increased by
      relaxation. This would result in an increase in arousal, the antithesis of
      relaxation. This paper suggests that relaxation techniques that avoid imagery or
      consider the patient's experience would be less likely to provoke unwanted
      reactions.

PMID- 9265612
TI  - The impact of exercise on a man's life span development.

PMID- 9265614
TI  - XVIth Nordic congress of cardiology. Tampere, Finland, June 11-13, 1997.
      Abstracts.

PMID- 9265613
TI  - Experience of mothers with early postnatal discharge: a study in progress.

PMID- 9265615
TI  - The solution phase interaction between apolipoprotein(a) and plasminogen inhibits
      the binding of plasminogen to a plasmin-modified fibrinogen surface.
AB  - In the present study, we assessed the binding of recombinant forms of
      apolipoprotein(a) [r-apo(a)] to plasminogen. Apo(a)-plasminogen interactions were
      demonstrated to be lysine-dependent, as they were abolished by the addition of
      epsilon-aminocaproic acid. Binding of r-apo(a) and plasma-derived Lp(a) to Glu
      plasminogen was assessed in solution using a mutant form of recombinant
      plasminogen [Plg(S741C)] labeled at the active site with 5'
      (iodoacetamido)fluorescein. High-affinity binding of apo(a) to plasminogen was
      observed with the 17-kringle r-apo(a) (Kd = 20.1 +/- 3.3 nM) as well as with
      plasma-derived Lp(a) (Kd = 5.58 +/- 0.08 nM). Binding studies using various
      truncated and mutant forms of r-apo(a) demonstrated that sequences within apo(a)
      kringle IV types 2-9 and the strong lysine binding site (LBS) in apo(a) kringle
      IV type 10 are not required for high-affinity binding to plasminogen. In all
      cases, the binding stoichiometry for the apo(a)-plasminogen interaction was
      determined to be 1:1. Binding data obtained using a 17-kringle r-apo(a)
      derivative lacking the protease-like domain (17KDeltaP; Kd = 3158 +/- 138 nM)
      indicate that sequences within the protease-like domain of apo(a) mediate its
      interaction with LBS in plasminogen. We determined that r-apo(a) and plasminogen
      bind to distinct sites on plasmin-modified fibrinogen with the concentration of
      plasminogen binding sites exceeding the concentration of r-apo(a) sites by a
      factor of 10. Furthermore, r-apo(a) is capable of inhibiting the binding of
      plasminogen to plasmin-modified fibrinogen surfaces, an effect which we show is
      attributable to the formation of a solution phase apo(a)/plasminogen complex
      which exhibits a greatly reduced affinity for plasminogen binding sites on
      plasmin-modified fibrinogen. The results of this study provide new insights into
      the mechanism by which apo(a) and Lp(a) may inhibit fibrinolysis, thus
      contributing to the atherothrombotic risk associated with this lipoprotein.

PMID- 9265616
TI  - Interactions between smooth muscle alpha-actinin and lipid bilayers.
AB  - alpha-Actinin has been proposed to be the actin-plasma membrane linker. This
      assumption is based on the discovery of direct interaction of alpha-actinin with
      two specific lipids, diacylglycerol and palmitic acid [Burn, P. (1988) Trends
      Biochem. Sci. 13, 79-83]. In our study, the binding of alpha-actinin with
      vesicles containing negatively charged phospholipids was measured by the method
      of 90 degrees light-scattering. Our results show that alpha-actinin is able to
      bind membranes containing negatively charged phospholipids, but not to bind
      membranes composed of neutral lipids only. Diacylglycerol and palmitic acid, on
      the other hand, have little effect on the binding of alpha-actinin to lipid
      vesicles. Analysis of binding isotherms in terms of a membrane binding model gave
      apparent dissociation constants which varied between 0.2 and 3 microM over a
      range of 5-20 mol % negatively charged phospholipid. Comparing the kinetics of
      alpha-chymotrypsin digestion of alpha-actinin in solution to those of vesicle
      bound alpha-actinin, it can be seen that the cleavage site at the junction
      between the C-terminal and the central rod domain of alpha-actinin and another
      cleavage site on the C-terminal domain can be most effectively protected by its
      membrane binding. Analysis of the amide I and II regions of Fourier-transform
      infrared spectra of alpha-actinin revealed that the association of alpha-actinin
      with negatively charged phospholipid vesicles resulted in some perturbation of
      the protein secondary structure. Monolayers containing negatively charged
      phospholipid were layered and incubated on the surface of a polymerization
      solution of actin and alpha-actinin, and observed with an electron microscope.
      The results show that the bundle structure of actin filaments can be formed if
      diacylglycerol and palmitic acid are present in lipid layers.

PMID- 9265617
TI  - Conformational studies of mono- and bicyclic parathyroid hormone-related protein
      derived agonists.
AB  - Parathyroid hormone-related protein (PTHrP) is expressed in a wide variety of
      cells where it acts as an autocrine and/or paracrine factor involved in
      regulation of cellular growth, differentiation, and embryonic development. It may
      also play a physiological endocrine role in calcium transport across the placenta
      or during lactation. The N-terminal portion, PTHrP-(1-34), retains all the
      calciotropic parathyroid hormone-like activity and is a lead structure for the
      design of novel, bone anabolic agents for the treatment of bone disorders such as
      osteoporosis. To characterize the putative bioactive conformation, we have
      carried out a detailed structural analysis of a series of three conformationally
      constrained PTHrP-(1-34)-based mono- and bicyclic lactam-containing biologically
      active analogs: (III) The conformational properties were studied by circular
      dichroisim, nuclear magnetic resonance spectroscopy, distance geometry
      calculations, and molecular dynamic simulations in water/trifluoroethanol (TFE)
      mixtures. The helical content in water of both monocyclic analogs I and II is
      approximately 22%; that of the bicyclic analog III is approximately 40%. In 30%
      TFE, all analogs reached a maximal helical content of 80%, corresponding to 26 or
      27 residues out of 34 in a helical conformation. High-resolution structures
      obtained with 50:50 TFE/water revealed that all three analogs display two helical
      domains and a hinge region around Gly12-Lys13. The highly potent mono- and
      bicyclic agonists I and III display a second hinge around Arg19-Arg20 which is
      shifted to Ser14-Asp17 in the weakly potent monocyclic agonist II. We suggest
      that the presence and localization of discrete hinges in the sequence together
      with the high propensity for helicity of the C-terminal sequence and the
      enhancement of helical nucleation at the N-terminal sequence are essential for
      generating a PTH/PTHrP receptor-compatible bioactive conformation.

PMID- 9265618
TI  - Carbonic anhydrase activators: X-ray crystallographic and spectroscopic
      investigations for the interaction of isozymes I and II with histamine.
AB  - The interaction of native and Co(II)-substituted isozymes I and II of carbonic
      anhydrase (CA) with histamine, a well-known activator, was investigated
      kinetically, spectroscopically, and X-ray crystallographically. This activator is
      of the noncompetitive type with 4-nitrophenyl acetate and CO2 as substrates for
      both HCA I and HCA II. The electronic spectrum of the adduct of Co(II)-HCA II
      with histamine is similar to the spectrum of the Co(II)-HCA II-phenol adduct,
      being only slightly different from that of the uncomplexed enzyme. This is the
      first spectroscopic evidence that the activator molecule binds within the active
      site, but not directly to the metal ion. X-ray crystallographic data for the
      adduct of HCA II with histamine showed that the activator molecule is bound at
      the entrance of the active site cavity in a position where it may actively
      participate in shuttling protons between the active site and the bulk solvent.
      The role of the activators and the reported X-ray crystal structure of the HCA II
      histamine adduct has prompted us to reexamine the X-ray structures of the
      different CA isozymes in order to find a structural basis accounting for their
      large differences in catalytic rate. A tentative explanation is proposed on the
      basis of possible pathways of proton transfer, which constitute the rate-limiting
      step in the catalytic reaction.

PMID- 9265619
TI  - Tertiary structure of RBD2 and backbone dynamics of RBD1 and RBD2 of the human
      U1A protein determined by NMR spectroscopy.
AB  - The human U1A protein has two putative RNA binding domains, one at the N-terminal
      region of the protein (RBD1) and the other at the C-terminal end (RBD2). RBD1
      binds tightly and specifically to one of the stem loops of the U1 snRNA, as well
      as to its own 3'-UTR. In contrast, RBD2 does not appear to associate with any
      RNA. The two domains share 25% amino acid identity, and both have the same
      betaalphabeta-betaalphabeta secondary structure fold. In this work, 13C/15N/1H
      multidimensional NMR methods were used to obtain side-chain assignments for RBD2,
      and then the tertiary structure was calculated using a distance
      geometry/simulated annealing algorithm that employs pairwise Gaussian
      metrization. RBD2 is shown to fold into an alpha/beta sandwich with a four
      stranded antiparallel beta-sheet, which is the typical global topology of these
      domains. Specific structural features of RBD2 include a beta-bulge in beta2, N
      capping boxes for both alpha-helices, and an extremely shallow twist of its beta
      sheet. The 15N backbone dynamics of these two structurally homologous RBDs are
      significantly different, compared using order parameters and T2 exchange terms in
      the Lipari and Szabo model-free formalism. Conformational exchange observed in
      RBD1, which is absent in RBD2, may correlate to the mechanism of RNA binding.

PMID- 9265620
TI  - Dissecting contributions to the thermostability of Pyrococcus furiosus
      rubredoxin: beta-sheet chimeras.
AB  - The contributions to thermostability of interactions within the beta-sheet region
      of rubredoxins (Rds) were investigated by examining proteins in which beta-strand
      sequences of Rds from the hyperthermophilic archaeon Pyrococcus furiosus (Pf) and
      the mesophilic bacterium Clostridium pasteurianum (Cp) were interchanged. The
      thermostabilities of the chimeric Rds were assessed by monitoring the decay of
      the visible absorbance at 490 nm and of the far-UV CD vs time at 92 degrees C.
      The chimeric Rds Pf15 Cp47 Pf (Pf Rd residues 2-15 and 48-54 and Cp Rd residues
      16-47) and Cp15 Pf47 Cp were both found to be far less thermostable than wild
      type Pf Rd, indicating that neither the beta-sheet residues (2-7, 10-15, and 48
      53) nor the "core residues" (16-47) of Pf Rd independently confer Pf Rd-like
      thermostability. However, the chimeric Rd Pf47 Cp exhibits thermostability close
      to that of wild-type Pf Rd, suggesting that Pf Rd-like thermostability is
      conferred by interactions of beta-sheet strands 1 and 2 (residues 2-15) together
      with Pf core residues. In contrast, Cp Rd beta-sheet strands 1 and 2 connecting
      to Pf Rd core residues are thermodestabilizing in the chimera Cp15 Pf Rd. These
      results suggest that a global alignment which optimizes both main chain and side
      chain interactions between beta-sheet strands and core residues is more important
      than a few localized interactions within the beta-sheet in conferring Pf Rd-like
      thermostability.

PMID- 9265621
TI  - Engineering the independent folding of the subtilisin BPN' prodomain: analysis of
      two-state folding versus protein stability.
AB  - In complex with subtilisin BPN', the 77 amino acid prodomain folds into a stable
      compact structure comprising a four-stranded antiparallel beta-sheet and two
      three-turn alpha-helices. When isolated from subtilisin, the prodomain is 97%
      unfolded even under optimal folding conditions. Traditionally, to study stable
      proteins, denaturing cosolvents or temperatures are used to shift the equilibrium
      from folded to unfolded. Here we manipulate the folding equilibrium of the
      unstable prodomain by introducing stabilizing mutations generated by design. By
      sequentially introducing three stabilizing mutations into the prodomain we are
      able to shift the equilibrium for independent folding from 97% unfolded to 65%
      folded. Spectroscopic and thermodynamic analysis of the folding reaction was
      carried out to assess the effect of stability on two-state behavior and the
      denatured state. The denatured states of single and combination mutants are not
      discernably different in spite of a range of DeltaGunfolding from -2.1 to 0.4
      kcal/mol. Conclusions about the nature of the denatured state of the prodomain
      are based on CD spectral data and calorimetric data. Two state folding is
      observed for a combination mutant of marginal stability (DeltaG = 0). Evidence
      for its two-state folding is based on the observed additivity of individual
      mutations to the overall DeltaGunfolding and the conformity of DeltaGunfolding vs
      T to two-state assumptions as embodied in the Gibbs-Helmholz equation. We believe
      our success in stabilizing the two-state folding reaction of the prodomain
      originates from the selection of mutations with improved ability to fold
      subtilisin rather than selection for increase in secondary structure content. The
      fact that a small number of mutations can stabilize the independent folding of
      the prodomain implies that most of the folding information already exists in the
      wild-type amino acid sequence in spite of the fact that the unfolded state
      predominates.

PMID- 9265623
TI  - Allosteric properties of inosine monophosphate dehydrogenase revealed through the
      thermodynamics of binding of inosine 5'-monophosphate and mycophenolic acid.
      Temperature dependent heat capacity of binding as a signature of ligand-coupled
      conformational equilibria.
AB  - The thermodynamic properties of binding of the substrate, inosine monophosphate
      (IMP), and the uncompetitive inhibitor, mycophenolic acid, to inosine
      monophosphate dehydrogenase (IMPDH) were measured. Specifically, the free energy,
      enthalpy, entropy, and heat capacity changes were determined for each ligation
      state of the tetrameric enzyme, over a temperature range from 2.5 to 37 degrees C
      by high-precision titration microcalorimetry. It was discovered that IMP binds to
      IMPDH in a negatively cooperative fashion and that mycophenolic acid binding is
      critically dependent on the presence of IMP. Moreover, the binding of IMP is
      entropically driven at low temperatures and enthalpically driven at high
      temperatures, with an unusually large, temperature dependent heat capacity
      change. A thermodynamic argument, based on the general nature of the heat
      capacity function for a binding reaction and its temperature dependence, is used
      to infer the existence of an equilibrium mixture of at least two structural forms
      of apo-IMPDH. The equilibrium is perturbed in the presence of IMP and
      mycophenolic acid, suggesting a mechanism for the ligand-linked conformational
      changes. An allosteric model, incorporating subunit-subunit interactions nested
      within a concerted conformational change involving the entire tetrameric
      macromolecule, is proposed to account for the observed binding behavior. The
      implications of these findings for the design of novel "allosteric-effector"
      inhibitors of IMPDH, to be used for the purpose of immunosuppression, are
      discussed.

PMID- 9265622
TI  - Kinetic mechanism for p38 MAP kinase.
AB  - p38 has been shown to be a critical enzyme in the pro-inflammatory cytokine
      pathway and is a member of the mitogen-activated protein (MAP) kinase family.
      While the details for p38 activation and subsequent signal transduction have
      begun to be elucidated, little is known about the kinetic mechanism for p38. In
      this study, we have determined the kinetic mechanism for p38 MAP kinase. Data
      from initial velocity patterns in the presence and absence of a dead-end
      inhibitor and two triarylimidazole p38 inhibitors were consistent with an ordered
      sequential mechanism for p38 with protein substrate, glutathione S-transferase
      activating transcription factor 2 (GST-ATF2), binding before ATP. The ATP analog,
      adenylyl methylenediphosphonate (AMP-PCP), and two triarylimidazoles were
      competitive inhibitors versus ATP and uncompetitive inhibitors versus GST-ATF2.
      Equilibrium binding studies utilizing a tritiated ATP-competitive inhibitor were
      also consistent with this mechanism and suggest an inability of ATP to bind to
      p38 in the absence of protein substrate. Moreover, the Michaelis constant for GST
      ATF2 was 12-fold greater than the dissociation constant, indicating that the
      binding of ATP affected the binding of GST-ATF2. An ordered sequential mechanism
      with protein substrate binding first is unique to p38 compared to cyclic AMP
      dependent protein kinase (cAPK) and most tyrosine kinases and helps to explain
      the interaction between enzyme, substrates, and inhibitors.

PMID- 9265624
TI  - Solution structure and backbone dynamics of the human alpha3-chain type VI
      collagen C-terminal Kunitz domain,.
AB  - The solution structure and backbone dynamics of the 58-residue C-terminal Kunitz
      domain fragment [alpha3(VI)] of human alpha3-chain type VI collagen has been
      studied by two-dimensional 1H-1H and 1H-15N nuclear magnetic resonance
      spectroscopy at 303 K. The solution structure is represented by an ensemble of 20
      structures calculated with X-PLOR using 612 distance and 47 dihedral angle
      restraints. The distance restraints were obtained by a complete relaxation matrix
      analysis using MARDIGRAS. The root mean squared (rms) deviation is 0.91 A for the
      backbone atoms of the residues Thr2(8)-Gly12(18), Arg15(21)-Tyr35(41), and
      Gly40(46)-Pro57(63). The central beta-sheet [residues Ile18(24)-Tyr35(41)] and
      the C-terminal alpha-helix [residues Gln48(54)-Cys55(61)] are better defined with
      a backbone rms deviation of 0.46 A. The solution structure of alpha3(VI) is
      virtually identical to the crystal structure of alpha3(VI) and to the solution
      structure of bovine pancreatic trypsin inhibitor (BPTI). The 15N spin-lattice and
      spin-spin relaxation rates and the 1H-15N heteronuclear nuclear Overhauser
      enhancement (NOE) were analyzed using both the "model-free" formalism [Lipari,
      G., & Szabo, A. (1982) J. Am. Chem. Soc. 104, 4546-4559 and 4559-4570] and the
      reduced spectral density mapping procedure [Farrow, N. A., Szabo, A., Torchia, D.
      A., & Kay, L. E. (1995) J. Biomol.NMR 6, 153-162]. The results obtained from the
      "model-free" analysis include an overall correlation time tauc of 3. 00 ns and
      backbone order parameters S2 in the range from 0.28 to 0. 93. The necessity of
      including an exchange term in the analysis of the relaxation data from 14
      residues indicated that these residues are involved in motions on the micro- to
      millisecond time scale. The majority of the 14 residues are located in the
      vicinity of the Cys14(20)-Cys38(44) disulfide bond, suggesting the presence of a
      disulfide bond isomerization similar to the one observed in BPTI [Otting, G.,
      Liepinsh, E., & Wuthrich, K. (1993) Biochemistry 32, 3571-3582]. It is suggested
      that this disulfide bond isomerization is the main reason for the surprisingly
      small effect on trypsin inhibition observed when Thr13(19) of alpha3(VI) is
      substituted with Pro.

PMID- 9265625
TI  - Structure-function analysis of Msx2-mediated transcriptional suppression.
AB  - Osteocalcin (OC) is a calcium binding protein expressed in mature osteoblasts
      undergoing mineralization. The OC gene has been identified as a target for
      transcriptional suppression by Msx2, a homeodomain transcription factor that
      controls ossification in calvarial bone of the developing skull. We have
      initiated systematic structure-function analyses of Msx2, using OC promoter
      suppression (luciferase reporter) in MC3T3-E1 calvarial osteoblasts as an assay.
      Msx2 variants were epitope ("FLAG")-tagged for monitoring Msx2 protein expression
      by Western blot analysis. Functional analyses of N- and C-terminally truncated
      molecules identify Msx2 residues 97-208 as the core suppressor domain. Internal
      deletion analyses indicate that suppressor function is dependent upon structural
      features encoded by residues 132-148--upstream of the homeodomain and overlapping
      the homeodomain N-terminal extension--but not upon residues in the three
      homeodomain helices. Mutations that enhance DNA binding activity do not
      proportionally enhance Msx2 suppressor function; moreover, a Msx2 point mutant
      Msx2(T147A) that completely lacks DNA binding activity is indistinguishable from
      wild-type Msx2 in its ability to suppress the OC promoter, demonstrating that
      direct interaction with DNA is not required for Msx2 suppressor function. This
      suggests that Msx2 suppresses transcription via protein-protein interactions with
      components of the basal transcriptional machinery, either alone or in concert
      with co-regulators. Using interaction "Far Western" blotting assays, we
      systematically tested for protein-protein interactions between Msx2 and
      components of the basal transcriptional machinery known to mediate
      transcriptional activation (TBP, TFIIB, and TFIIF). Msx2 binds both components of
      TFIIF (RAP74, RAP30), but not TFIIB or TBP. Msx2(55-208) encompasses core
      suppressor domain residues and binds TFIIF; in this context, deletion of the
      seventeen amino acid residues 132-148 that are required for core suppressor
      function abrogates interactions with TFIIF components. Co-expression of RAP74 in
      MC3T3-E1 cells partially reverses (>50%) suppression of OC promoter activity by
      Msx2, while co-expression of TFIIB or RAP30 has no effect. Thus the core
      suppressor domain of Msx2 participates in functionally important interactions
      with RAP74 that regulate OC promoter activity in calvarial osteoblasts.

PMID- 9265626
TI  - Structural modification changes the DNA binding mode of cation-substituted
      anthraquinone photonucleases: association by intercalation or minor groove
      binding determines the DNA cleavage efficiency.
AB  - The mode of binding anthraquinone derivatives, bearing positively charged
      ammonium side chains, to duplex DNA was investigated by optical and NMR
      spectroscopy. Absorption, circular dichroism, emission, and one- and two
      dimensional homonuclear NMR spectroscopy show that mono- and dication-substituted
      quinones, AQS and 27AQS, bind primarily by intercalation. In contrast, these
      experiments indicate that the tetracationic anthraquinone 27AQS2 is bound
      nonintercalatively to duplex DNA. In particular, analysis of the NMR spectrum of
      27AQS2 bound to a specially designed synthetic self-complementary
      dodecanucleotide (5'-CGCGAATTCGCG-3') shows it to be associated primarily with
      the minor groove of the central AATT sequence. The change in the DNA binding mode
      greatly affects the photophysical and photochemical properties of these
      photonucleases with DNA.

PMID- 9265627
TI  - Residues at the carboxy terminus of T4 DNA polymerase are important determinants
      for interaction with the polymerase accessory proteins.
AB  - Three T4 DNA polymerase accessory proteins (44P/62P and 45P) stimulate the
      polymerase (pol) activity and the 3'-5' exonuclease (exo) activity of T4 DNA
      polymerase (43P) on long, double-stranded DNA substrates. The 44P/62P "clamp
      loader" facilitates the binding of 45P, the "sliding clamp", to DNA that is
      primed for replication. Using a series of truncated 43P mutants, we identified a
      region at the extreme carboxy terminus of the DNA polymerase that is required for
      its interaction with accessory proteins. Truncation mutants of 43P lacking the
      carboxy-terminal 3, 6, or 11 residues retained full pol and exo activity on short
      synthetic primer-templates. However, the ability of the accessory proteins to
      enhance these activities on long double-stranded DNA templates was drastically
      reduced, and the extent of the reduction in activity was greater as more residues
      were deleted. One of the truncation mutants (N881), which had 17 residues removed
      from the carboxy terminus, showed reduced binding affinity and diminished pol
      activity but enhanced exo activity upon incubation with a small primer-template.
      The exo activity of the N881 mutant, on short, single-stranded DNA was unchanged,
      however, compared to the wild-type enzyme. These results are consistent with
      inferences drawn from the crystal structure of a DNA polymerase from a related T
      even phage, RB69, where the carboxy-terminal 12 residues (equivalent to the 11
      residues of 43P from phage T4) protrude from the thumb domain and are free to
      interact with complementary surfaces of the accessory proteins. The structural
      integrity of the thumb region in the N881 mutant is probably perturbed and could
      account for its reduced binding affinity and pol activity when incubated with
      short, double-stranded DNA substrates.

PMID- 9265628
TI  - Zinc binding properties of the DNA binding domain of the 1,25-dihydroxyvitamin D3
      receptor.
AB  - To assess the zinc binding stoichiometry and the structural changes induced upon
      the binding of zinc to the human vitamin D receptor (VDR), we expressed the DNA
      binding domain (DBD) of the human VDR in bacteria as a soluble glutathione-S
      transferase fusion protein at 20 degrees C, and examined the apo-protein and
      metal-liganded protein by mass spectrometry, and circular dichroism and nuclear
      magnetic resonance spectroscopy. Following final preparation with a zinc-free
      buffer, the VDR DBD bound 2 mol of zinc/mol of protein as measured by inductively
      coupled plasma-mass spectrometry and electrospray ionization-mass spectrometry.
      When protein preparation was carried out in a zinc containing buffer and zinc
      content of the protein was assesed by the same methods, VDR DBD bound 4 mol of
      zinc/mol of protein. Analysis of the protein using circular dichroism
      spectroscopy demonstrated that the EDTA-treated protein increased in alpha
      helical content from 16 to 27% on the addition of zinc. Equilibrium
      ultracentrifugal analyses of the VDR DBD indicated that the protein was present
      in solution as a monomer. Gel mobility shift analyses of the VDR DBD with several
      vitamin D response elements (VDREs) in the absence of accessory proteins such as
      retinoic acid receptor, showed that VDR DBD was able to form a protein/VDRE DNA
      structural complex. In the presence of zinc, proton NMR NOESY spectra showed that
      the protein possessed elements of secondary structure. The addition of VDRE DNA,
      but not random DNA, caused changes in the proton NMR spectra of VDRE DNA
      indicating specific interaction between protein and DNA groups. We conclude that
      the DBD of the VDR binds zinc and DNA and undergoes conformational changes on
      binding to the metal and DNA.

PMID- 9265629
TI  - Three tRNA binding sites in rabbit liver ribosomes and role of the intrinsic
      ATPase in 80S ribosomes from higher eukaryotes.
AB  - Three tRNA binding sites have been found in organisms of all domains (former
      kingdoms) with only one exception: Four binding sites have been reported for
      cytoplasmic 80S ribosomes from rabbit liver. Therefore, the issue was
      reconsidered, and the data revealed that rabbit liver ribosomes contain three
      tRNA binding sites, underlining the universal character of this ribosomal
      feature. Furthermore, a first analysis of the role of the ribosome intrinsic
      ATPase was performed. This ATPase is found in ribosomes of higher eukarya but not
      in lower eukarya such as yeast or ribosomes of the domains archea and bacteria.
      The results suggest that the intrinsic ATPase fulfills the same function as the
      essential third elongation factor EF-3, an ATPase in higher fungi (yeast etc.),
      that facilitates the release of the deacylated tRNA from the E site.

PMID- 9265631
TI  - Tight binding of folate substrates and inhibitors to recombinant mouse
      glycinamide ribonucleotide formyltransferase.
AB  - The binding of the prototypical folate inhibitor of de novo purine synthesis,
      5,10-dideazatetrahydrofolate (DDATHF), and its hexaglutamate to recombinant
      trifunctional mouse glycinamide ribonucleotide formyltransferase (rmGARFT) was
      studied by equilibrium dialysis and by steady-state kinetics using sensitive
      assays that allowed initial rate calculations. rmGARFT was expressed in insect
      cells infected with a recombinant baculovirus and purified by a two-step
      procedure that allowed production of about 25 mg of pure protein/L of culture.
      The binding of DDATHF to GARFT was approximately 50-fold tighter than previously
      reported, with Kd and Ki values of 2-9 nM, making the parent form of this
      antifolate a tight-binding inhibitor. The binding of the hexaglutamate of DDATHF
      to rmGARFT had Kd and Ki values of 0.1-0.3 nM, consistent with the view that
      polyglutamation enhances binding of antifolates to GARFT. Kinetic analyses using
      either mono- or hexaglutamate substrate did not yield different values for the Ki
      for the hexaglutamate form of DDATHF, in contradiction with previous reports.
      Both the folate substrate commonly used to study GARFT, 10-formyl-5,8
      dideazafolate, and its hexaglutamate were found to have very low Km values,
      namely, 75 and 7.4 nM, respectively, and the folate reaction products for these
      substrates were equally potent inhibitors, results which modify the
      interpretation of previous kinetic experiments. The product analog DDATHF and
      beta-glycinamide ribonucleotide bound to enzyme equally well in the presence and
      absence of the other, an observation at variance with the concept that GARFT
      obeys an ordered sequential binding of the substrates. We conclude that the
      kinetics of mouse GARFT are most consistent with a random order of substrate
      binding, that both the inhibitor DDATHF and the folate substrate are tight
      binding ligands, and that polyglutamate forms enhance the affinity of both
      substrate and inhibitor by an order of magnitude.

PMID- 9265630
TI  - Mutational analysis of potential zinc-binding residues in the active site of the
      enterococcal D-Ala-D-Ala dipeptidase VanX.
AB  - VanX, one of the five proteins required for the vancomycin-resistant phenotype in
      clinically pathogenic Enterococci, is a zinc-containing d-Ala-d-Ala dipeptidase.
      To identify potential zinc ligands and begin defining the active site residues,
      we have mutated the 2 cysteine, 5 histidine, and 4 of the 28 aspartate and
      glutamate residues in the 202 residue VanX protein. Of 10 mutations, 3 cause
      inactivation and greater than 90% loss of zinc in purified enzyme samples,
      implicating His116, Asp123, and His184 as zinc-coordinating residues. Homology
      searches using the 10 amino acid sequence SxHxxGxAxD, in which histidine and
      aspartate residues are putative zinc ligands, identified the metal coordinating
      ligands in the N-terminal domain of the murine Sonic hedgehog protein, which also
      exhibits an architecture for metal coordination identical to that observed in
      thermolysin from Bacillus thermoproteolyticus. Furthermore, this 10 amino acid
      consensus sequence is found in the Streptomyces albus G zinc-dependent N-acyl-d
      Ala-d-Ala carboxypeptidase, an enzyme catalyzing essentially the same d-Ala-d-Ala
      dipeptide bond cleavage as VanX, suggesting equivalent mechanisms and zinc
      catalytic site architectures. VanX residue Glu181 is analogous to the Glu143
      catalytic base in B. thermoproteolyticus thermolysin, and the E181A VanX mutant
      has no detectable dipeptidase activity, yet maintains near-stoichiometric zinc
      content, a result consistent with the participation of the residue as a catalytic
      base.

PMID- 9265632
TI  - Noncoded amino acid replacement probes of the aspartate aminotransferase
      mechanism.
AB  - The primary role of Tyr225 in the aspartate aminotransferase mechanism is to
      provide a hydrogen bond to stabilize the 3'O- functionality of bound pyridoxal
      phosphate. The strength of this hydrogen bond is perturbed by replacement of
      Tyr225 with 3-fluoro-L-tyrosine (FlTyr) by in vitro transcription/translation.
      This mutant enzyme exhibits kcat/values that are near to those of wild type
      enzyme; however, the kcat/vs pH profile is much sharper with similar pKas of
      approximately 7.5 for both the ascending and descending limbs. The pKas are
      assigned to the endocyclic proton of the internal aldimine and to the bridging
      hydrogen bond, respectively. The pKas in the kcat vs pH profile of 7.2 and 8.7
      are assigned to the epsilon-NH3+ of lysine 258 and to the endocyclic protons of
      the ketimine complex, respectively. Arginine 292 forms a salt bridge with the
      beta-COOH of the substrate, aspartate. An improvement on the earlier attempt to
      invert the substrate charge specificity via R292D mutation-induced arginine
      transaminase activity [Cronin, C. N., & Kirsch, J. F. (1988) Biochemistry 27,
      4572-4579] is described. Here Arg292 is replaced with homoglutamate (R292hoGlu).
      This construct exhibits 6.8 x 10(4)-fold greater activity for the cationic
      substrate D,L-[Calpha-3H]-alpha-amino-beta-guanidinopropionic acid (D,L-[Calpha
      3H]AGPA) than does wild type enzyme. The gain in selectivity for this substrate
      is at least 4500-fold greater than that achieved in the 1988 experiment, i.e.,
      [(kcat/KM)R292hoGlu/(kcat/KM)WT (D,L-[Calpha-3H]AGPA)] >/= 4500 x
      [(kcat/KM)R292D/(kcat/KM)WT (L-arginine)]. The value of (kcat/KM)R292D is 0.43 M
      1 s-1 with L-Arg while (kcat/KM)R292hoGlu is 29 M-1 s-1 with D,L-[Calpha-3H]AGPA
      (it is assumed that the D-enantiomer is unreactive). The latter value is the
      lower limit because of the uncertain value of 3H kinetic isotope effect.

PMID- 9265633
TI  - Structure and function of ubiquitin conjugating enzyme E2-25K: the tail is a core
      dependent activity element.
AB  - Individual members of the conserved family of ubiquitin conjugating enzymes (E2s)
      mediate the ubiquitination and turnover of specific substrates of the ubiquitin
      dependent degradation pathway. E2 proteins have a highly conserved core domain of
      approximately 150 amino acids which contains the active-site Cys. Certain E2s
      have unique terminal extensions, which are thought to contribute to selective E2
      function by interacting either with substrates or with trans-acting factors such
      as ubiquitin-protein ligases (E3s). We used the mammalian ubiquitin conjugating
      enzyme E2-25K in a biochemical test of this hypothesis. The properties of two
      truncated derivatives show that the 47-residue tail of E2-25K is necessary for
      three of the enzyme's characteristic properties: high activity in the synthesis
      of unanchored K48-linked polyubiquitin chains; resistance of the active-site Cys
      residue to alkylation; and an unusual discrimination against noncognate
      (nonmammalian) ubiquitin activating (E1) enzymes. However, the tail is not
      sufficient to generate these properties, as shown by the characteristics of a
      chimeric enzyme in which the tail of E2-25K was fused to the core domain of yeast
      UBC4. These and other results indicate that the specific biochemical function of
      the tail is strongly dependent upon unique features of the E2-25K core domain.
      Thus, divergent regions within the conserved core domains of E2 proteins may be
      highly significant for function. Expression of truncated E2-25K as a glutathione
      S-transferase (GST) fusion protein resulted in the apparent recovery of E2-25K
      specific properties, including activity in chain synthesis. However, the
      catalytic mechanism utilized by the truncated fusion protein proved to be
      distinct from the mechanism utilized by the wild-type enzyme. The unexpected
      properties of the fusion protein were due to GST-induced dimerization. These
      results indicate the potential for self-association to modulate the polyubiquitin
      chain synthesis activities of E2 proteins, and indicate that caution should be
      applied in interpreting the activities of GST fusion proteins.

PMID- 9265634
TI  - 3-Phosphohistidine cannot replace phosphotyrosine in high-affinity binding to
      phosphotyrosine binding or Src homology 2 domains.
AB  - Posttranslational phosphorylation of proteins is an important event in many
      cellular processes. Phosphorylated tyrosine residues can serve as association
      sites for other proteins in signal transduction cascades of tyrosine kinase
      receptors. Formation of phosphohistidine residues in proteins has been found in
      eukaryotic and prokaryotic organisms. Furthermore, it has been suggested that
      phosphohistidine might substitute for phosphotyrosine in conferring high-affinity
      binding to proteins involved in signal transduction. We have analyzed the ability
      of 3-phosphohistidine to associate with the known phosphotyrosine-specific
      phosphotyrosine binding and src homology 2 protein domains. From our binding
      studies using synthetic peptides, we conclude that 3-phosphohistidine cannot
      replace phosphotyrosine in conferring high-affinity binding to the
      phosphotyrosine binding domain of shc or the src homology 2 domain of
      phospholipase C-gamma1.

PMID- 9265635
TI  - Cisplatin complexes with phosphatidylserine in membranes.
AB  - Upon incubation of the anticancer drug cisplatin [cis
      diamminedichloroplatinum(II)] with model membranes composed of phosphatidylserine
      (PS), a stable product is formed that has been isolated after chloroform/methanol
      extraction of the sample. The product formation is specific for PS and does not
      occur with other major membrane phospholipids. The rate and extent of product
      formation is dependent on the pH, chloride ion concentration, and temperature,
      with the highest rate at pH 6.0, in the absence of Cl- and at 37 degrees C,
      indicating that positively charged aquated cisplatin is the reactive species.
      Over 80% of PS is converted within 15 h under these conditions with a halftime of
      5 h. PS can be regenerated by an excess of glutathione. Mass spectrometry
      experiments demonstrate that interaction of cisplatin with PS involves a loss of
      two chloride ions and coordination of platinum to the amine and carboxyl group of
      the serine moiety. Cisplatin forms complexes specifically with PS not only in
      model membranes but also in the plasma membrane of human erythrocytes. Since PS
      is essential in several cellular processes, its interaction with cisplatin may
      have important physiological implications.

PMID- 9265636
TI  - Changes in vesicle morphology induced by lateral phase separation modulate
      phospholipase A2 activity.
AB  - The action of phospholipase A2 (PLA2) toward zwitterionic bilayers is modulated
      by lateral phase separation of reaction products and substrate. The experiments
      here address the mechanism of this modulation. PLA2 is particularly active toward
      lipid dispersions containing reaction products and substrates in which lateral
      phase separation has occurred. Here, we study PLA2 activity in two related model
      systems: first in a system in which lateral phase separation can be produced a
      priori, and second in a system in which the action of PLA2 produces sufficient
      reaction product in situ such that lateral phase separation occurs. The
      dispersions in which lateral phase separation occurs a priori form either disk
      micelles or disk vesicles, not canonical vesicles. When lateral phase separation
      occurs due to in situ PLA2 activity, there is an abrupt change in vesicle
      structure and a simultaneous profound increase in catalytic rate. This
      observation is surprising in light of several reports that vesicles remain intact
      even when the entire outer monolayer has been hydrolyzed. Membrane curvature and
      the associated structural defects and dynamic fluctuations in membrane structure
      have been proposed to modulate PLA2 activity. The mechanism by which lateral
      phase separation modulates PLA2 activity has been unclear. The data presented
      here indicate that lateral phase separation affects PLA2 activity by altering
      membrane curvature and/or inducing defects in the membrane structure.

PMID- 9265638
TI  - Alkaline transition of Rhus vernicifera stellacyanin, an unusual blue copper
      protein.
AB  - Stellacyanin from Rhus vernificera is a blue copper protein in which the metal is
      coordinated to a Cys, two His, and a Gln residue. It displays a low redox
      potential, a fast electron exchange rate, and a reversible alkaline transition.
      We have studied this transition in Cu(II)- and Co(II)-stellacyanin by means of
      electronic and NMR spectroscopy. The data indicate that a conformational
      rearrangement of the metal site occurs at high pH. A drastic alteration in the
      Gln coordination mode, as initially proposed, is discarded. These results show
      that the metal site in stellacyanin is more flexible than the sites of other blue
      copper proteins. The present study demonstrates that the paramagnetic shifts of
      the bound Cys in the Co(II) derivative are sensitive indicators of the electron
      delocalization and conformational changes experienced by this residue.

PMID- 9265637
TI  - Altering the binuclear manganese cluster of arginase diminishes thermostability
      and catalytic function.
AB  - Arginase is a thermostable (Tm = 75 degrees C) binuclear manganese metalloenzyme
      which hydrolyzes l-arginine to form l-ornithine and urea. The three-dimensional
      structures of native metal-depleted arginase, metal-loaded H101N arginase, and
      metal-depleted H101N arginase have been determined by X-ray crystallographic
      methods to probe the roles of the manganese ion in site A (Mn2+A) and its ligand
      H101 in catalysis and thermostability. We correlate these structures with thermal
      stability and catalytic activity measurements reported here and elsewhere
      [Cavalli, R. C., Burke, C. J., Kawamoto, S., Soprano, D. R., and Ash, D. E.
      (1994) Biochemistry 33, 10652-10657]. We conclude that the substitution of a wild
      type histidine ligand to Mn2+A compromises metal binding, which in turn
      compromises protein thermostability and catalytic function. Therefore, a fully
      occupied binuclear manganese metal cluster is required for optimal catalysis and
      thermostability.

PMID- 9265639
TI  - Interaction of nascent ApoE2, ApoE3, and ApoE4 isoforms expressed in mammalian
      cells with amyloid peptide beta (1-40). Relevance to Alzheimer's disease.
AB  - Population studies have established that one of the common isoforms of
      apolipoprotein E, the apoE4, is associated with higher incidence and earlier age
      of onset of late onset familial Alzheimer's disease (AD), whereas apoE2 may have
      the opposite effect. The apoE3 and apoE4 isoforms were shown to display different
      binding reactivities with amyloid beta peptide (Abeta) and tau protein in vitro.
      On the basis of these findings, it has been proposed that the apoE isoforms may
      modulate positively or negatively the formation of either the neurofibrillary
      tangles or the amyloid deposits in the brain of patients with AD. To study the
      interaction of Abeta with nascent apoE isoforms we have expressed their cDNAs in
      baby hamster kidney (BHK-21) cells using the Semliki Forest Virus expression
      system. Analysis of the secreted apoE by one- and two-dimensional gel
      electrophoresis and immunoblotting showed that the nascent apoE is heavily
      modified with carbohydrate chains containing sialic acid. A dimeric form of apoE
      is formed with apoE2 and apoE3 but not with apoE4 isoforms. Analysis of the
      interaction of nascent apoE2, apoE3, and apoE4 produced by BHK-21 cells with
      Abeta (1-40) under physiological conditions (pH 7.4, 37 degrees C) showed that
      the efficiency of the apoE monomer-Abeta complex formation follows the order
      apoE2 > apoE3 >> apoE4. In addition, the apoE2 dimer formed a complex with Abeta
      more efficiently than the apoE3 dimer. The isoform-specific differences in
      binding were temperature-dependent and are attenuated upon decrease of the
      temperature. The binding behavior of the monomeric apoE is different from that
      reported for plasma apoE3 and apoE4 or commercially available apoE3 and apoE4
      preparations and similar to that described for apoE3 and apoE4 produced by human
      embryonic kidney (HEK-293) cells. It appears that the efficiency of binding
      between each of three main apoE isoforms and Abeta correlates inversely with the
      risk of developing late-onset familial AD and may indicate possible involvement
      of apoE in the binding and clearance of Abeta in vivo.

PMID- 9265640
TI  - Thermodynamics and NMR of internal G.T mismatches in DNA.
AB  - Thermodynamics of 39 oligonucleotides with internal G.T mismatches dissolved in 1
      M NaCl were determined from UV absorbance versus temperature profiles. These data
      were combined with literature values of six sequences to derive parameters for 10
      linearly independent trimer and tetramer sequences with G.T mismatches and Watson
      Crick base pairs. The G.T mismatch parameters predict DeltaG degrees 37, DeltaH
      degrees , DeltaS degrees , and TM with average deviations of 5.1%, 7.5%, 8.0%,
      and 1.4 degrees C, respectively. These predictions are within the limits of what
      can be expected for a nearest-neighbor model. The data show that the contribution
      of a single G.T mismatch to helix stability is context dependent and ranges from
      +1.05 kcal/mol for AGA/TTT to -1.05 kcal/mol for CGC/GTG. Several tests of the
      applicability of the nearest-neighbor model to G.T mismatches are described.
      Analysis of imino proton chemical shifts show that structural perturbations from
      the G.T mismatches are highly localized. One-dimensional NOE difference spectra
      demonstrate that G.T mismatches form stable hydrogen-bonded wobble pairs in
      diverse contexts. Refined nearest-neighbor parameters for Watson-Crick base pairs
      are also presented.

PMID- 9265641
TI  - Posttranslational modification of oat phytochrome A: phosphorylation of a
      specific serine in a multiple serine cluster.
AB  - Phytochrome A (phyA) is a photoreceptor of higher plants which mediates a variety
      of biochemical and physiological processes in response to red/far-red light. By
      detailed structural analysis of the peptides of the total tryptic digest of oat
      phyA, we found that the photoreceptor isolated from red light irradiated
      seedlings contains only one site of phosphate attachment, in the N-terminal Ser
      rich region. The N-terminal tryptic phosphopeptide (residues 1-12) contains eight
      serine residues, any of which may be phosphorylated. Direct fast atom bombardment
      mass spectrometry (FAB MS/MS) analysis of the phosphorylated peptide as well as
      of its phosphate-containing fragment (residues 1-9) was not successful due to
      their hydrophilic nature and instability of the phosphate bond. beta-Elimination
      of the phosphorylated tryptic peptide in the presence of ethanethiol converted
      the phosphoserine residue to S-ethylcysteine that is stable under FAB MS/MS. FAB
      MS/MS analysis of the modified peptide clearly showed that the phosphate group
      was attached to Ser7. The in vivo phosphorylation site at Ser7 in oat phyA is
      discussed for its possible regulatory role in phyA function.

PMID- 9265643
TI  - Apical enrichment of human EGF precursor in Madin-Darby canine kidney cells
      involves preferential basolateral ectodomain cleavage sensitive to a
      metalloprotease inhibitor.
AB  - EGF precursor (proEGF) is a member of the family of membrane-anchored EGF-like
      growth factors that bind with high affinity to the epidermal growth factor
      receptor (EGFR). In contrast to human transforming growth factor-alpha precursor
      (proTGFalpha), which is sorted basolaterally in Madin-Darby canine kidney (MDCK)
      cells (Dempsey, P., and R. Coffey, 1994. J. Biol. Chem. 269:16878-16889), we now
      demonstrate that human proEGF overexpressed in MDCK cells is found predominantly
      at the apical membrane domain under steady-state conditions. Nascent proEGF (185
      kD) is not sorted but is delivered equally to the apical and basolateral
      membranes, where it is proteolytically cleaved within its ectodomain to release a
      soluble 170-kD EGF form into the medium. Unlike the fate of TGFalpha in MDCK
      cells, the soluble 170-kD EGF species accumulates in the medium, does not
      interact with the EGFR, and is not processed to the mature 6-kD peptide. We show
      that the rate of ectodomain cleavage of 185-kD proEGF is fourfold greater at the
      basolateral surface than at the apical surface and is sensitive to a
      metalloprotease inhibitor, batimastat. Batimastat dramatically inhibited the
      release of soluble 170-kD EGF into the apical and basal medium by 7 and 60%,
      respectively, and caused a concordant increase in the expression of 185-kD proEGF
      at the apical and basolateral cell surfaces of 150 and 280%, respectively. We
      propose that preferential ectodomain cleavage at the basolateral surface
      contributes to apical domain localization of 185-kD proEGF in MDCK cells, and
      this provides a novel mechanism to achieve a polarized distribution of cell
      surface membrane proteins under steady-state conditions. In addition, differences
      in disposition of EGF and TGFalpha in polarized epithelial cells offer a new
      conceptual framework to consider the actions of these polypeptide growth factors.

PMID- 9265642
TI  - Novel genes involved in endosomal traffic in yeast revealed by suppression of a
      targeting-defective plasma membrane ATPase mutant.
AB  - A novel genetic selection was used to identify genes regulating traffic in the
      yeast endosomal system. We took advantage of a temperature-sensitive mutant in
      PMA1, encoding the plasma membrane ATPase, in which newly synthesized Pma1 is
      mislocalized to the vacuole via the endosome. Diversion of mutant Pma1 from
      vacuolar delivery and rerouting to the plasma membrane is a major mechanism of
      suppression of pma1(ts). 16 independent suppressor of pma1 (sop) mutants were
      isolated. Identification of the corresponding genes reveals eight that are
      identical with VPS genes required for delivery of newly synthesized vacuolar
      proteins. A second group of SOP genes participates in vacuolar delivery of mutant
      Pma1 but is not essential for delivery of the vacuolar protease carboxypeptidase
      Y. Because the biosynthetic pathway to the vacuole intersects with the endocytic
      pathway, internalization of a bulk membrane endocytic marker FM 4-64 was assayed
      in the sop mutants. By this means, defective endosome-to-vacuole trafficking was
      revealed in a subset of sop mutants. Another subset of sop mutants displays
      perturbed trafficking between endosome and Golgi: impaired pro-alpha factor
      processing in these strains was found to be due to defective recycling of the
      trans-Golgi protease Kex2. One of these strains defective in Kex2 trafficking
      carries a mutation in SOP2, encoding a homologue of mammalian synaptojanin
      (implicated in synaptic vesicle endocytosis and recycling). Thus, cell surface
      delivery of mutant Pma1 can occur as a consequence of disturbances at several
      different sites in the endosomal system.

PMID- 9265644
TI  - Acid-induced dissociation of VacA, the Helicobacter pylori vacuolating cytotoxin,
      reveals its pattern of assembly.
AB  - In this study, we describe the ultrastructural changes associated with acid
      activation of Helicobacter pylori vacuolating cytotoxin (VacA). Purified VacA
      molecules imaged by deep-etch electron microscopy form approximately 30-nm
      hexagonal "flowers," each composed of an approximately 15-nm central ring
      surrounded by six approximately 6-nm globular "petals." Upon exposure to acidic
      pH, these oligomeric flowers dissociate into collections of up to 12 teardrop
      shaped subunits, each measuring approximately 6 x 14 nm. Correspondingly,
      glycerol density gradient centrifugation shows that at neutral pH VacA sediments
      at approximately 22 S, whereas at acidic pH it dissociates and sediments at
      approximately 5 S. Immunoblot and EM analysis of the 5-S material demonstrates
      that it represents approximately 90-kD monomers with 6 x 14-nm "teardrop"
      morphology. These data indicate that the intact VacA oligomer consists of 12
      approximately 90-kD subunits assembled into two interlocked six-membered arrays,
      overlap of which gives rise to the flower-like appearance. Support for this
      interpretation comes from EM identification of small numbers of relatively "flat"
      oligomers composed of six teardrop-shaped subunits, interpreted to be halves of
      the complete flower. These flat forms adsorb to mica in two different
      orientations, corresponding to hexameric surfaces that are either exposed or
      sandwiched inside the dodecamer, respectively. This view of VacA structure
      differs from a previous model in which the flowers were interpreted to be single
      layers of six monomers and the flat forms were thought to be proteolysed flowers.
      Since acidification has been shown to potentiate the cytotoxic effects of VacA,
      the present results suggest that physical disassembly of the VacA oligomer is an
      important feature of its activation.

PMID- 9265645
TI  - Cofilin changes the twist of F-actin: implications for actin filament dynamics
      and cellular function.
AB  - Cofilin is an actin depolymerizing protein found widely distributed in animals
      and plants. We have used electron cryomicroscopy and helical reconstruction to
      identify its binding site on actin filaments. Cofilin binds filamentous (F)-actin
      cooperatively by bridging two longitudinally associated actin subunits. The
      binding site is centered axially at subdomain 2 of the lower actin subunit and
      radially at the cleft between subdomains 1 and 3 of the upper actin subunit. Our
      work has revealed a totally unexpected (and unique) property of cofilin, namely,
      its ability to change filament twist. As a consequence of this change in twist,
      filaments decorated with cofilin have much shorter 'actin crossovers' (
      approximately 75% of those normally observed in F-actin structures). Although
      their binding sites are distinct, cofilin and phalloidin do not bind
      simultaneously to F-actin. This is the first demonstration of a protein that
      excludes another actin-binding molecule by changing filament twist. Alteration of
      F-actin structure by cofilin/ADF appears to be a novel mechanism through which
      the actin cytoskeleton may be regulated or remodeled.

PMID- 9265646
TI  - Actin filament cables in Drosophila nurse cells are composed of modules that
      slide passively past one another during dumping.
AB  - At a late stage in Drosophila oogenesis, nurse cells rapidly expel their
      cytoplasm into the oocyte via intracellular bridges by a process called nurse
      cell dumping. Before dumping, numerous cables composed of actin filaments appear
      in the cytoplasm and extend inward from the plasma membrane toward the nucleus.
      This actin cage prevents the nucleus, which becomes highly lobed, from physically
      blocking the intracellular bridges during dumping. Each cable is composed of a
      linear series of modules composed of approximately 25 cross-linked actin
      filaments. Adjacent modules overlap in the cable like the units of an extension
      ladder. During cable formation, individual modules are nucleated from the cell
      surface as microvilli, released, and then cross-linked to an adjacent forming
      module. The filaments in all the modules in a cable are unidirectionally
      polarized. During dumping as the volume of the cytoplasm decreases, the nucleus
      to plasma membrane distance decreases, compressing the actin cables that shorten
      as adjacent modules slide passively past one another just as the elements of an
      extension ladder slide past one another for storage. In Drosophila, the modular
      construction of actin cytoskeletons seems to be a generalized strategy. The
      behavior of modular actin cytoskeletons has implications for other actin-based
      cytoskeletal systems, e.g., those involved in Listeria movement, in cell
      spreading, and in retrograde flow in growth cones and fibroblasts.

PMID- 9265647
TI  - Drosophila kelch is an oligomeric ring canal actin organizer.
AB  - Drosophila kelch has four protein domains, two of which are found in kelch-family
      proteins and in numerous nonkelch proteins. In Drosophila, kelch is required to
      maintain ring canal organization during oogenesis. We have performed a structure
      function analysis to study the function of Drosophila kelch. The amino-terminal
      region (NTR) regulates the timing of kelch localization to the ring canals.
      Without the NTR, the protein localizes precociously and destabilizes the ring
      canals and the germ cell membranes, leading to dominant sterility. The amino half
      of the protein including the BTB domain mediates dimerization. Oligomerization
      through the amino half of kelch might allow cross-linking of ring canal actin
      filaments, organizing the inner rim cytoskeleton. The kelch repeat domain is
      necessary and sufficient for ring canal localization and likely mediates an
      additional interaction, possibly with actin.

PMID- 9265648
TI  - Gelsolin modulates phospholipase C activity in vivo through phospholipid binding.
AB  - Gelsolin and CapG are actin regulatory proteins that remodel the cytoskeleton in
      response to phosphatidylinositol 4,5-bisphosphate (PIP2) and Ca2+ during agonist
      stimulation. A physiologically relevant rise in Ca2+ increases their affinity for
      PIP2 and can promote significant interactions with PIP2 in activated cells. This
      may impact divergent PIP2- dependent signaling processes at the level of
      substrate availability. We found that CapG overexpression enhances PDGF
      stimulated phospholipase Cgamma (PLCgamma) activity (Sun, H.-q., K. Kwiatkowska,
      D.C. Wooten, and H.L. Yin. 1995. J. Cell Biol. 129:147-156). In this paper, we
      examined the ability of gelsolin and CapG to compete with another PLC for PIP2 in
      live cells, in semiintact cells, and in vitro. We found that CapG and gelsolin
      overexpression profoundly inhibited bradykinin-stimulated PLCbeta. Inhibition
      occurred at or after the G protein activation step because overexpression also
      reduced the response to direct G protein activation with NaF. Bradykinin
      responsiveness was restored after cytosolic proteins, including gelsolin, leaked
      out of the overexpressing cells. Conversely, exogenous gelsolin added to
      permeabilized cells inhibited response in a dose-dependent manner. The washout
      and addback experiments clearly establish that excess gelsolin is the primary
      cause of PLC inhibition in cells. In vitro experiments showed that gelsolin and
      CapG stimulated as well as inhibited PLCbeta, and only gelsolin domains
      containing PIP2-binding sites were effective. Inhibition was mitigated by
      increasing PIP2 concentration in a manner consistent with competition between
      gelsolin and PLCbeta for PIP2. Gelsolin and CapG also had biphasic effects on
      tyrosine kinase- phosphorylated PLCgamma, although they inhibited PLCgamma less
      than PLCbeta. Our findings indicate that as PIP2 level and availability change
      during signaling, cross talk between PIP2-regulated proteins provides a selective
      mechanism for positive as well as negative regulation of the signal transduction
      cascade.

PMID- 9265649
TI  - Tubulin subunits exist in an activated conformational state generated and
      maintained by protein cofactors.
AB  - The production of native alpha/beta tubulin heterodimer in vitro depends on the
      action of cytosolic chaperonin and several protein cofactors. We previously
      showed that four such cofactors (termed A, C, D, and E) together with native
      tubulin act on beta-tubulin folding intermediates generated by the chaperonin to
      produce polymerizable tubulin heterodimers. However, this set of cofactors
      generates native heterodimers only very inefficiently from alpha-tubulin folding
      intermediates produced by the same chaperonin. Here we describe the isolation,
      characterization, and genetic analysis of a novel tubulin folding cofactor
      (cofactor B) that greatly enhances the efficiency of alpha-tubulin folding in
      vitro. This enabled an integrated study of alpha- and beta-tubulin folding: we
      find that the pathways leading to the formation of native alpha- and beta-tubulin
      converge in that the folding of the alpha subunit requires the participation of
      cofactor complexes containing the beta subunit and vice versa. We also show that
      sequestration of native alpha-or beta-tubulins by complex formation with
      cofactors results in the destabilization and decay of the remaining free subunit.
      These data demonstrate that tubulin folding cofactors function by placing and/or
      maintaining alpha-and beta-tubulin polypeptides in an activated conformational
      state required for the formation of native alpha/beta heterodimers, and imply
      that each subunit provides information necessary for the proper folding of the
      other.

PMID- 9265650
TI  - Identification of a microtubule-associated motor protein essential for dendritic
      differentiation.
AB  - The quintessential feature of the dendritic microtubule array is its nonuniform
      pattern of polarity orientation. During the development of the dendrite, a
      population of plus end-distal microtubules first appears, and these microtubules
      are subsequently joined by a population of oppositely oriented microtubules.
      Studies from our laboratory indicate that the latter microtubules are
      intercalated within the microtubule array by their specific transport from the
      cell body of the neuron during a critical stage in development (Sharp, D.J., W.
      Yu, and P.W. Baas. 1995. J. Cell Biol. 130:93- 104). In addition, we have
      established that the mitotic motor protein termed CHO1/MKLP1 has the appropriate
      properties to transport microtubules in this manner (Sharp, D.J., R. Kuriyama,
      and P.W. Baas. 1996. J. Neurosci. 16:4370-4375). In the present study we have
      sought to determine whether CHO1/MKLP1 continues to be expressed in terminally
      postmitotic neurons and whether it is required for the establishment of the
      dendritic microtubule array. In situ hybridization analyses reveal that
      CHO1/MKLP1 is expressed in postmitotic cultured rat sympathetic and hippocampal
      neurons. Immunofluorescence analyses indicate that the motor is absent from axons
      but is enriched in developing dendrites, where it appears as discrete patches
      associated with the microtubule array. Treatment of the neurons with antisense
      oligonucleotides to CHO1/MKLP1 suppresses dendritic differentiation, presumably
      by inhibiting the establishment of their nonuniform microtubule polarity pattern.
      We conclude that CHO1/MKLP1 transports microtubules from the cell body into the
      developing dendrite with their minus ends leading, thereby establishing the
      nonuniform microtubule polarity pattern of the dendrite.

PMID- 9265651
TI  - PSTPIP: a tyrosine phosphorylated cleavage furrow-associated protein that is a
      substrate for a PEST tyrosine phosphatase.
AB  - We have investigated proteins which interact with the PEST-type protein tyrosine
      phosphatase, PTP hematopoietic stem cell fraction (HSCF), using the yeast two
      hybrid system. This resulted in the identification of proline, serine, threonine
      phosphatase interacting protein (PSTPIP), a novel member of the actin- associated
      protein family that is homologous to Schizosaccharomyces pombe CDC15p, a
      phosphorylated protein involved with the assembly of the actin ring in the
      cytokinetic cleavage furrow. The binding of PTP HSCF to PSTPIP was induced by a
      novel interaction between the putative coiled-coil region of PSTPIP and the COOH
      terminal, proline-rich region of the phosphatase. PSTPIP is tyrosine
      phosphorylated both endogenously and in v-Src transfected COS cells, and
      cotransfection of dominant-negative PTP HSCF results in hyperphosphorylation of
      PSTPIP. This dominant-negative effect is dependent upon the inclusion of the COOH
      terminal, proline-rich PSTPIP-binding region of the phosphatase. Confocal
      microscopy analysis of endogenous PSTPIP revealed colocalization with the
      cortical actin cytoskeleton, lamellipodia, and actin-rich cytokinetic cleavage
      furrow. Overexpression of PSTPIP in 3T3 cells resulted in the formation of
      extended filopodia, consistent with a role for this protein in actin
      reorganization. Finally, overexpression of mammalian PSTPIP in exponentially
      growing S. pombe results in a dominant-negative inhibition of cytokinesis. PSTPIP
      is therefore a novel actin-associated protein, potentially involved with
      cytokinesis, whose tyrosine phosphorylation is regulated by PTP HSCF.

PMID- 9265652
TI  - The synaptic protein syntaxin1 is required for cellularization of Drosophila
      embryos.
AB  - Syntaxins are membrane proteins involved in vesicle trafficking and are required
      for the release of neurotransmitter at nerve terminals. The presence of syntaxins
      on target membranes has been hypothesized to confer specificity to targeting and
      fusion via interactions with complementary vesicle-associated proteins, the
      synaptobrevins or VAMPS. We have mutagenized syntaxin1 in Drosophila and have
      found that it links the mechanism of synaptic transmission to a distinct cell
      biological process: the cellularization of early embryos. This specialized form
      of cell division separates the 6,000 nuclei of the syncytial blastoderm into
      separate cells through the invagination of the surface membrane of the embryo.
      During this process, syntaxin1 protein is present on the newly forming lateral
      cell surfaces and invaginating cleavage furrows. This protein is derived both
      from maternal deposition of mRNA and protein and from early zygotic
      transcription. To analyze syntaxin1's role in early development, female germ line
      mosaics mutant for syntaxin1 expression were generated by mitotic recombination
      to reduce the maternal contribution. Visualizing the actin cytoskeleton and
      glycosylated surface proteins reveals that embryos with insufficient syntaxin1
      have large acellular patches. The patches do not appear until cellularization
      begins, and the process fails entirely within these regions. These results
      provide genetic evidence that membrane trafficking is required for the
      cellularization of the syncytial blastoderm. We propose that the invagination of
      the surface membrane proceeds by the fusion of intracellular membrane vesicles
      with the surface. This reaction uses the same syntaxin1 protein as is required
      for neurotransmitter secretion at synapses. Thus, a single syntaxin can
      participate in trafficking steps that are functionally as distinct as synaptic
      transmission and cell division.

PMID- 9265653
TI  - A new function for the LDL receptor: transcytosis of LDL across the blood-brain
      barrier.
AB  - Lipoprotein transport across the blood-brain barrier (BBB) is of critical
      importance for the delivery of essential lipids to the brain cells. The
      occurrence of a low density lipoprotein (LDL) receptor on the BBB has recently
      been demonstrated. To examine further the function of this receptor, we have
      shown using an in vitro model of the BBB, that in contrast to acetylated LDL,
      which does not cross the BBB, LDL is specifically transcytosed across the
      monolayer. The C7 monoclonal antibody, known to interact with the LDL receptor
      binding domain, totally blocked the transcytosis of LDL, suggesting that the
      transcytosis is mediated by the receptor. Furthermore, we have shown that
      cholesterol-depleted astrocytes upregulate the expression of the LDL receptor at
      the BBB. Under these conditions, we observed that the LDL transcytosis parallels
      the increase in the LDL receptor, indicating once more that the LDL is
      transcytosed by a receptor-mediated mechanism. The nondegradation of the LDL
      during the transcytosis indicates that the transcytotic pathway in brain
      capillary endothelial cells is different from the LDL receptor classical pathway.
      The switch between a recycling receptor to a transcytotic receptor cannot be
      explained by a modification of the internalization signals of the cytoplasmic
      domain of the receptor, since we have shown that LDL receptor messengers in
      growing brain capillary ECs (recycling LDL receptor) or differentiated cells
      (transcytotic receptor) are 100% identical, but we cannot exclude
      posttranslational modifications of the cytoplasmic domain, as demonstrated for
      the polymeric immunoglobulin receptor. Preliminary studies suggest that caveolae
      are likely to be involved in the potential transport of LDL from the blood to the
      brain.

PMID- 9265654
TI  - COOH terminus of occludin is required for tight junction barrier function in
      early Xenopus embryos.
AB  - Occludin is the only known integral membrane protein localized at the points of
      membrane- membrane interaction of the tight junction. We have used the Xenopus
      embryo as an assay system to examine: (a) whether the expression of mutant
      occludin in embryos will disrupt the barrier function of tight junctions, and (b)
      whether there are signals within the occludin structure that are required for
      targeting to the sites of junctional interaction. mRNAs transcribed from a series
      of COOH-terminally truncated occludin mutants were microinjected into the antero
      dorsal blastomere of eight-cell embryos. 8 h after injection, the full-length and
      the five COOH-terminally truncated proteins were all detected at tight junctions
      as defined by colocalization with both endogenous occludin and zonula occludens-1
      demonstrating that exogenous occludin correctly targeted to the tight junction.
      Importantly, our data show that tight junctions containing four of the COOH
      terminally truncated occludin proteins were leaky; the intercellular spaces
      between the apical cells were penetrated by sulfosuccinimidyl-6-(biotinamido)
      Hexanoate (NHS-LC-biotin). In contrast, embryos injected with mRNAs coding for
      the full-length, the least truncated, or the soluble COOH terminus remained
      impermeable to the NHS-LC-biotin tracer. The leakage induced by the mutant
      occludins could be rescued by coinjection with full-length occludin mRNA.
      Immunoprecipitation analysis of detergent-solubilized embryo membranes revealed
      that the exogenous occludin was bound to endogenous Xenopus occludin in vivo,
      indicating that occludin oligomerized during tight junction assembly. Our data
      demonstrate that the COOH terminus of occludin is required for the correct
      assembly of tight junction barrier function. We also provide evidence for the
      first time that occludin forms oligomers during the normal process of tight
      junction assembly. Our data suggest that mutant occludins target to the tight
      junction by virtue of their ability to oligomerize with full-length endogenous
      molecules.

PMID- 9265655
TI  - Loss of matrix adhesion triggers rapid transformation-selective apoptosis in
      fibroblasts.
AB  - Cell-matrix and cell-cell adhesion are recognized physiological determinants of
      cell growth and survival. In epithelial and endothelial cell systems, oncogenic
      transformation has in several cases been shown to confer resistance to apoptosis
      upon depriving cells of substrate adhesion. We examined the effects of oncogenic
      transformation in adherent versus adhesion- deprived primary embryonic
      fibroblasts. Whereas untransformed early passage fibroblasts undergo cell cycle
      arrest, their Myc/Ras- or E1A/Ras-transformed counterparts rapidly enter
      apoptosis when placed into suspension. This phenomenon also occurs upon
      incubation with a soluble, RGD-containing integrin ligand and is blocked by a
      peptide antagonist to ICE family proteases or by aggregation of cells plated at
      high density. Loss of wild-type p53 modulates the kinetics but does not abrogate
      this death pathway. Transformation with activated Src rather than Ras rendered
      fibroblasts selectively resistant to adhesion-dependent apoptosis, an effect
      likely related to Src's role in integrin signaling, while simultaneously
      sensitizing the cells to radiation-induced apoptosis. Thus cell adhesion events
      regulate transformation-selective apoptosis in fibroblasts and provide
      potentially important targets for understanding and interfering with tumor cell
      viability.

PMID- 9265656
TI  - Role of actin polymerization and adhesion to extracellular matrix in Rac- and Rho
      induced cytoskeletal reorganization.
AB  - Most animal cells use a combination of actin-myosin-based contraction and actin
      polymerization- based protrusion to control their shape and motility. The small
      GTPase Rho triggers the formation of contractile stress fibers and focal adhesion
      complexes (Ridley, A.J., and A. Hall. 1992. Cell. 70:389-399) while a close
      relative, Rac, induces lamellipodial protrusions and focal complexes in the
      lamellipodium (Nobes, C.D., and A. Hall. 1995. Cell. 81:53-62; Ridley, A.J., H.F.
      Paterson, C.L. Johnston, D. Diekmann, and A. Hall. 1992. Cell. 70:401-410); the
      Rho family of small GTPases may thus play an important role in regulating cell
      movement. Here we explore the roles of actin polymerization and extracellular
      matrix in Rho- and Rac-stimulated cytoskeletal changes. To examine the underlying
      mechanisms through which these GTPases control F-actin assembly, fluorescently
      labeled monomeric actin, Cy3-actin, was introduced into serum-starved Swiss 3T3
      fibroblasts. Incorporation of Cy3- actin into lamellipodial protrusions is
      concomitant with F-actin assembly after activation of Rac, but Cy3-actin is not
      incorporated into stress fibers formed immediately after Rho activation. We
      conclude that Rac induces rapid actin polymerization in ruffles near the plasma
      membrane, whereas Rho induces stress fiber assembly primarily by the bundling of
      actin filaments. Activation of Rho or Rac also leads to the formation of integrin
      adhesion complexes. Integrin clustering is not required for the Rho-induced
      assembly of actin-myosin filament bundles, or for vinculin association with actin
      bundles, but is required for stress fiber formation. Integrin-dependent focal
      complex assembly is not required for the Rac-induced formation of lamellipodia or
      membrane ruffles. It appears, therefore, that the assembly of large integrin
      complexes is not required for most of the actin reorganization or cell morphology
      changes induced by Rac or Rho activation in Swiss 3T3 fibroblasts.

PMID- 9265657
TI  - Rho- and rac-dependent assembly of focal adhesion complexes and actin filaments
      in permeabilized fibroblasts: an essential role for ezrin/radixin/moesin
      proteins.
AB  - The small GTPases Rho and Rac regulate actin filament assembly and the formation
      of integrin adhesion complexes to produce stress fibers and lamellipodia,
      respectively, in mammalian cells. Although numerous candidate effectors that
      might mediate these responses have been identified using the yeast two-hybrid and
      affinity purification techniques, their cellular roles remain unclear. We now
      describe a biological assay that allows components of the Rho and Rac signaling
      pathways to be identified. Permeabilization of serum-starved Swiss 3T3 cells with
      digitonin in the presence of guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS)
      induces both actin filament and focal adhesion complex assembly through
      activation of endogenous Rho and Rac. These responses are lost when GTPgammaS is
      added 6 min after permeabilization, but can be reconstituted using concentrated
      cytosolic extracts. We have achieved a 10,000-fold purification of the activity
      present in pig brain cytosol and protein sequence analysis shows it to contain
      moesin. Using recombinant proteins, we show that moesin and its close relatives
      ezrin and radixin can reconstitute stress fiber assembly, cortical actin
      polymerization and focal complex formation in response to activation of Rho and
      Rac.

PMID- 9265658
TI  - The cell adhesion molecule DdCAD-1 in Dictyostelium is targeted to the cell
      surface by a nonclassical transport pathway involving contractile vacuoles.
AB  - DdCAD-1 is a 24-kD Ca2+-dependent cell- cell adhesion molecule that is expressed
      soon after the initiation of development in Dictyostelium cells. DdCAD-1 is
      present on the cell surface as well as in the cytosol. However, the deduced amino
      acid sequence of DdCAD-1 lacks a hydrophobic signal peptide or any predicted
      transmembrane domain, suggesting that it may be presented on the cell surface via
      a nonclassical transport mechanism. Here we report that DdCAD-1 is transported to
      the cell surface via contractile vacuoles, which are normally involved in
      osmoregulation. Immunofluorescence microscopy and subcellular fractionation
      revealed a preferential association of DdCAD-1 with contractile vacuoles.
      Proteolytic treatment of isolated contractile vacuoles degraded vacuole
      associated calmodulin but not DdCAD-1, demonstrating that DdCAD-1 was present in
      the lumen. The use of hyperosmotic conditions that suppress contractile vacuole
      activity led to a dramatic decrease in DdCAD-1 accumulation on the cell surface
      and the absence of cell cohesiveness. Shifting cells back to a hypotonic
      condition after hypertonic treatments induced a rapid increase in DdCAD-1
      positive contractile vacuoles, followed by the accumulation of DdCAD-1 on the
      cell membrane. 7-chloro-4-nitrobenzo-2-oxa-1, 3-diazole, a specific inhibitor of
      vacuolar-type H+-ATPase and thus of the activity of contractile vacuoles, also
      inhibited the accumulation of DdCAD-1 on the cell surface. Furthermore, an in
      vitro reconstitution system was established, and isolated contractile vacuoles
      were shown to import soluble DdCAD-1 into their lumen in an ATP-stimulated
      manner. Taken together, these data provide the first evidence for a nonclassical
      protein transport mechanism that uses contractile vacuoles to target a soluble
      cytosolic protein to the cell surface.

PMID- 9265659
TI  - Three-dimensional contrast-enhanced magnetic resonance angiography of the
      thoracic vasculature.
AB  - Magnetic resonance angiography (MRA) has become a useful non-invasive imaging
      technique for the assessment of vascular disease. Due to limitations such as
      respiratory motion artefacts, saturations problems, and long acquisition times,
      applications of MRA in the thorax have largely been restricted to imaging of the
      aorta. The recent introduction of breath-hold three-dimensional (3D) contrast
      enhanced MRA promises not only to enhance conventional MR protocols for aortic
      imaging, but to extend the clinical indications of MRI to diseases affecting
      other vascular structures of the thorax, most notably the pulmonary arteries.
      This article describes the technical aspects of contrast-enhanced 3D MRA and
      reviews existing and potential future clinical applications.

PMID- 9265660
TI  - Noninvasive stress testing of myocardial ischemia: comparison of GRE-MRI
      perfusion and wall motion analysis to 99 mTc-MIBI-SPECT, relation to coronary
      angiography.
AB  - In the evaluation of ischemic heart disease only MR imaging seems to have the
      potential to assess myocardial perfusion, function, and coronary morphology on a
      single instrument. The aim of this study was to assess the feasibility of a
      stress test with dipyridamole (0. 56 mg/kg) to analyze myocardial perfusion by Gd
      first-pass enhancement in ultrafast gradient-recalled-echo MRI (perf-MRI), and
      wall motion by cine gradient-recalled-echo MRI (Cine-MRI) in one imaging session.
      Twelve patients underwent complete rest and stress studies; satisfactory MR
      images were acquired in 10 patients. By 99 mTc-MIBI-SPECT sensitivities to detect
      ischemic segments were 66.7 % with Perf-MRI, 80.0 % with WM-MRI and 86.7 % for
      Perf-WM-MRI (Perf-MRI vs Perf-WM-MRI; p = 0.03). Scar was equally detected with a
      sensitivity of 91.6 % with either MRI technique. Thus, Perf-Cine-MRI provides
      complementary information for the management of ischemic heart disease and has a
      higher sensitivity than Perf-MRI alone.

PMID- 9265661
TI  - Catheter-directed lysis of iliofemoral vein thrombosis with use of rt-PA.
AB  - The aim of our study was to evaluate the results of catheter-directed
      thrombolysis and complementary procedures to treat acute iliofemoral deep vein
      thrombosis (DVT). A total of 24 consecutive patients with acute iliofemoral DVT
      underwent intrathrombus drip infusion of alteplase (3 mg/h; mean dosage 86 mg,
      range 45-174 mg), while intravenous heparin (1000 U/h) was continued.
      Complementary procedures were hydrodynamic thrombectomy in 3 and primary
      insertion of a Wallstent in 9 patients. Patency of 19 thrombosed veins (79 %) was
      restored with prompt symptomatic relief. An underlying anatomical anomaly or
      lesion was present in 13 patients: iliac vein compression syndrome (n = 8),
      absent (n = 2) or obstructed (n = 1) vena cava or venous stenosis (n = 2). Ten of
      the abnormalities were unknown before lysis and eight were relieved by stent
      deployment. Puncture site bleeding was the only complication but led to
      transfusion in 6 patients (25 %). Symptomatic reocclusion occurred in 4 patients.
      Catheter thrombolysis of iliofemoral vein thrombosis revealed many anatomical
      abnormalities which may predispose to thrombosis and are often amenable to
      stenting.

PMID- 9265662
TI  - Prognostic value of contrast-enhanced MR mammography in patients with breast
      cancer.
AB  - The objective of this study was to evaluate the prognostic value of contrast
      enhanced MR mammography in patients with breast cancer. A total of 190 patients
      with breast cancer (37 noninvasive carcinomas, 153 invasive carcinomas) underwent
      dynamic contrast-enhanced MR mammography preoperatively. Using 1.5-T unit, T1
      weighted sequences (2D FLASH) were obtained repeatedly one time before and five
      times after IV administration of 0.1 mmol gadopentetate-dimeglumine per kilogram
      body weight. The findings on MR imaging were correlated with histopathologically
      defined prognostic factors (histological type, tumor size, tumor grading,
      metastasis in lymph nodes). In addition, immunohistochemically defined prognostic
      factors (c-erbB-1, c-erbB-2, p53, Ki-67) were correlated with the signal increase
      on MR mammogram in 40 patients. There was no significant correlation between the
      findings on MR mammography and the histopathological type of carcinoma, the
      grading, and the lymphonodular status. Noninvasive carcinomas showed a higher
      rate of moderate (38 %) or low (27 %) enhancement on MR imaging than invasive
      carcinomas (6 and 3 %). The results on MR mammography and the results of
      immunohistochemical stainings did not correlate significantly. Noninvasive
      carcinomas showed significantly lower enhancement than invasive carcinomas.
      However, the signal behavior of contrast-enhanced MR mammography is not related
      to established histopathological prognostic parameters as subtyping, grading,
      nodal status, and the expression of certain oncogenes/tumor suppressor genes.

PMID- 9265663
TI  - Paraffin tissue block radiography of nonpalpable lesions with calcifications
      detected at mammography: 5-year consecutive series of surgically excised cases.
AB  - The objective of our study was to evaluate paraffin tissue block radiography
      following biopsy for breast calcifications at a center for population-based
      mammography screening. During a 5-year period, we radiographed tissue blocks from
      259 breast specimens excised because of nonpalpable calcifications. A total of
      124 cases were examined retrospectively and 135 cases were examined
      prospectively. In 34 of 94 (36 %) retrospectively examined cases with
      calcifications, the histopathological diagnosis was ductal cancer in situ with or
      without invasive cancer, compared with 3 of 30 (10 %) cases without
      calcifications. In 6 cases a primary benign histopathological diagnosis was
      changed to malignant due to the use of tissue block radiography. Tissue block
      radiography is a valuable adjunctive method to assure that areas containing
      calcifications are examined by histopathology.

PMID- 9265664
TI  - Idiopathic granulomatous mastitis.
AB  - A case of idiopathic granulomatous mastitis mimicking breast carcinoma clinically
      and radiographically is reported with mammography, sonography and MR images.

PMID- 9265665
TI  - New concepts in understanding evolution of desmoid tumors: MR imaging of 30
      lesions.
AB  - The objective of this study was to evaluate the appearance and the natural
      evolution of desmoid tumors on MR imaging, given histologic correlation. The MR
      images of 30 desmoids (20 primary and 10 recurrent) in 26 patients were scored
      for a multiplicity of morphological parameters, signal intensity (SI) on
      different pulse sequences, and behavior after contrast administration. Natural
      evolution was evaluated in 2 primary and 3 recurrent lesions, and correlated with
      evolution on histologic specimens. Desmoid tumors are mostly found in muscles of
      shoulder and hip girdle and are often fusiform with partially ill-defined
      margins. Rare subcutaneous desmoids have a more stellar morphology. Variable
      amounts of low-SI areas are present on all sequences. On T1-weighted images (T1
      WI), most lesions are near homogeneous and isointense to muscle, whereas on T2-WI
      they are more heterogeneous with an overall SI equal to or slightly lower than
      fat. Histologic correlation reveals that SI on T2-WI cannot be explained solely
      by cellularity. After initial growth, spontaneous evolution of desmoids is
      characterized by shrinking and an increase in low-SI areas on T2-WI. While distal
      lesions shrink, the more recent lesions in asynchronous multicentric desmoids
      have a tendency to develop proximally in the same limb, and should not be
      confused with recurrences. Fast growth, extracompartmental spread, and bone
      involvement are often seen in recurrences. Follow-up MR imaging of desmoids
      indicates natural regression of desmoids and more aggressive behavior of
      recurrences, which may justify a more conservative therapeutic approach.

PMID- 9265667
TI  - Unusual high signal intensity on MR images in a patient with multiple tendinous
      xanthomas.
AB  - The MR features of a 57-year-old man with multiple tendinous xanthomas are
      reported. The lesions of the peroneus longus tendons and the Achilles tendons
      showed diffuse reticulated pattern, which is the typical MR finding of tendinous
      xanthomas. However, the lesions of the patellar tendons showed no diffuse pattern
      and contained focal regions of high signal intensity on T 1-weighted images
      suggesting the deposition of triglycerides. The regions showed high signal
      intensity on T 2-weighted images and moderate enhancement on contrast-enhanced T
      1-weighted images suggesting the presence of associated inflammation.

PMID- 9265666
TI  - MRI of normal anterior cruciate ligament (ACL) and reconstructed ACL: comparison
      of when the knee is extended with when the knee is flexed.
AB  - The purpose of this study was to evaluate, using MRI, the morphology of normal
      anterior cruciate ligament (ACL) and ACL grafts when the knee was extended
      compared with when the knee was flexed. Eighteen normal controls and 22 ACL graft
      patients were studied. Spin-echo (SE) T1-weighted images (TR 330 ms/TE 15 ms, NEX
      1) were obtained with a slice thickness of 3 mm. Oblique sagittal images parallel
      to the ACL were obtained at various flexed angles of the knee joint. In 12 of the
      18 normal controls the ACL appeared convex toward the posterior side when the
      knee was extended and gradually became straight when the knee was flexed. In 15
      of the 22 ACL graft patients the grafts appeared straight when the knee was
      extended and became convex toward the anterior side when the knee was flexed. It
      is concluded that the morphological changes seen on MR images of ACL grafts from
      when the knee is extended to when the knee is flexed are different from those in
      the normal ACL.

PMID- 9265668
TI  - Chondrosarcoma causing cervical neural foramen widening.
AB  - Various neoplastic, vascular, and developmental causes may lead to spinal neural
      foraminal widening, the most common causes of spinal dumbbell lesions being
      schwannomas and neurofibromas. Occasionally, some other slow-growing tumors may
      cause neural foraminal widening. We report an exceptional case of a low-grade
      spinal chondrosarcoma which apparently developed from a pre-existing
      osteochondroma in the neural arcus of C6. The lesion passed through the C5-C6
      foramen, producing a dumbbell mass.

PMID- 9265669
TI  - Giant schwannoma of the lower leg.
AB  - Schwannomas are relatively common, benign, peripheral nerve sheath tumours. They
      usually range in size from 2 to 20 cm, but when localised in the lower legs the
      maximum length is less than 10 cm. The case reported here was a giant fusiform
      schwannoma of the left fibular nerve with a length of 25.5 cm. In contrast to the
      usual findings of giant schwannomas, no cystic, haemorrhagic or necrotic changes
      could be found by ultrasonography, computed tomography or magnetic resonance
      imaging. The combination of tumour size, location and radiological presentation
      is very unusual and, to our knowledge, has never been reported before in the
      literature.

PMID- 9265670
TI  - Perianal complications of Crohn disease: MR imaging findings.
AB  - The aim of this study was to revisit anal anatomy, to explain surgical
      terminology in perianal complications of Crohn disease, and to show the MR
      imaging findings of perianal fistulas and abscesses. To this end more than 200
      patients were studied using surface coils (Helmholtz; phased array) at 1.0 and
      1.5 T. Transverse and coronal T1- and T2-weighted images were obtained. Parks'
      classification was used to describe perianal abscesses and fistulas. This
      pictorial essay shows the normal anal anatomy and pathologic findings such as
      subcutaneous, para-anal, ischiorectal, intersphincteric, and supralevatoric
      abscesses and fistulas. MR imaging with surface coils is well suited to showing
      the anal anatomy and to reliably describing perianal abscesses and fistulas
      according to surgical terminology.

PMID- 9265671
TI  - Computed tomography of the normal appendix and acute appendicitis.
AB  - The aim of this article is to present pictorially the spectrum of appearances of
      the appendix and appendicitis on CT. The images presented were selected from the
      database of our hospitals. The various appearances of the normal appendix on CT
      are shown. Appendicitis can be divided into four categories on the basis of CT
      findings. Examples of each category are shown.

PMID- 9265672
TI  - T1-weighted spoiled gradient-echo MR imaging of focal hepatic lesion: comparison
      of in-phase vs opposed-phase pulse sequence.
AB  - The goal of our prospective study was to compare quantitatively and qualitatively
      in-phase and opposed-phase T1-weighted breath-hold spoiled gradient-recalled-echo
      (GRE) MR imaging technique for imaging focal hepatic lesion. Thirty-eight
      patients with 53 focal hepatic lesions had in-phase (TR = 12.3 ms, TE = 4.2 ms)
      and opposed-phase (TR = 10.1 ms, TE = 1.9 ms) GRE (flip angle = 30 degrees ,
      bandwidth +/- 32 kHz, matrix size 256 x 128, one signal average) MR imaging at
      1.5 T. Images were analyzed quantitatively by measuring the lesion-to-liver
      contrast and for lesion detection. In addition, images were reviewed
      qualitatively for lesion conspicuity. Quantitatively, lesion-to-liver contrast
      obtained with in-phase (3. 22 +/- 1.86) and opposed-phase pulse sequence (3.72 +/
      2.32) were not statistically different (Student's t-test). No difference in
      sensitivity was found between in-phase and opposed-phase pulse sequence (31 of
      53, sensitivity 58 % vs 30 of 53, sensitivity 57 %, respectively). Two lesions
      not seen with opposed-phase imaging were detected with in-phase imaging.
      Conversely, one lesion not seen on in-phase imaging was detected on opposed-phase
      imaging so that the combination of in-phase and opposed-phase imaging yielded
      detection of 32 of 53 lesions (sensitivity 60 %). Qualitatively, lesion
      conspicuity was similar with both techniques. However, in-phase images showed
      better lesion conspicuity than opposed-phase images in 9 cases, and opposed-phase
      images showed better lesion conspicuity than in-phase images in 7 cases. No
      definite advantage (at a significant level) emerged between in-phase and opposed
      phase spoiled GRE imaging. Because differences in lesion conspicuity and lesion
      detection may be observed with the two techniques in individual cases, MR
      evaluation of patients with focal hepatic lesion should include both in-phase and
      opposed-phase spoiled GRE imaging.

PMID- 9265673
TI  - Small bowel obstruction: role and contribution of sonography.
AB  - The purpose of this study was to determine whether sonography provides additional
      clinical information in patients suspected of small bowel (SB) obstruction.
      During a period of 30 months, in a prospective setting, we evaluated with
      sonography 123 patients suspected of SB obstruction. Sonographic examinations of
      the entire abdomen were performed with state-of-the-art, real-time, grey-scale
      equipment. Fourteen patients were labelled 'gassy' and no added information was
      provided following abdominal ultrasound. Sonography confirmed the SB obstruction
      in 82 cases with 5 false positives, resulting in a specificity of 82.1 %.
      Sonographic examinations were negative in 27 cases with 4 false negatives and a
      sensitivity of 95 %. The accuracy was 91.7 % when the 'gassy' patients were
      excluded and 81.3 % overall. The aetiology of the ileus was detected by
      sonography in 13 cases of paralytic ileus (54.1 %) and in 57 cases of mechanical
      ileus (71.4 %). It is concluded that ultrasound, which is a non-invasive,
      portable and even bedside imaging procedure, appears accurate in confirming a SB
      obstruction and in determining the aetiology of SB obstruction.

PMID- 9265674
TI  - Polyarteritis nodosa presenting with hemobilia and intestinal hemorrhage.
AB  - Polyarteritis nodosa is a multisystem disease primarily involving the small and
      medium-sized vessels. Prognosis depends on the presence and severity of visceral
      involvement. Thrombosis and aneurysm formation commonly occur in kidney and
      gastrointestinal tract. Although hepatic involvement is also common, hepatic
      aneurysmal rupture with intrahepatic or perihepatic hematoma formation is
      infrequent. Hemobilia secondary to aneurysmal rupture is a very rare condition.
      We present a case of polyarteritis nodosa accompanied by hemobilia and intestinal
      hemorrhage secondary to hepatic and mesenteric aneurysmal rupture.

PMID- 9265675
TI  - Esophageal hemangioma.
AB  - We report a case of esophageal hemangioma presenting with dysphagia and
      odynophagia. To our knowledge, very few cases have been reported in the
      radiological literature.

PMID- 9265676
TI  - Aberrant pancreas in the gallbladder wall.
AB  - We present three cases of heterotopic pancreas in the gallbladder wall. The
      patients (all female) presented with abdominal pain. Ultrasonography revealed
      polypoid tumor with coexistence of lithiasis in two cases. All patients underwent
      cholecystectomy. Microscopy revealed chronic cholecystitis and cholesteatosis and
      heterotopic pancreatic tissue. Heterotopic pancreas in the gallbladder wall is a
      rare heterotopia, with 23 cases reported in the international literature.

PMID- 9265677
TI  - Percutaneous treatment of a congenital splenic cyst with alcohol: a new
      therapeutic approach.
AB  - Percutaneous treatment of a huge congenital splenic cyst in a 23-year-old man is
      presented. The cyst had been catheterized and drained two times within a 3-month
      period without injecting any sclerosing agent into the cavity. On the third
      attempt, catheter drainage and injection of alcohol into the cyst cavity were
      performed because of insufficient response to drainage alone. He was discharged
      symptom-free after the procedure. The cyst diminished in size considerably 9
      months after the treatment with alcohol. The volume of the cyst was reduced from
      5200 to 8 ml. Although percutaneous treatment of a congenital splenic cyst with
      tetracyclin has been reported, to our knowledge this is the first case of a
      congenital splenic cyst treated with alcohol as a sclerosing agent. Percutaneous
      treatment of splenic cyst can obviate the need for partial or total splenectomy
      and may be an alternative to surgical treatment.

PMID- 9265678
TI  - Transcatheter liver lobar ablation: an experimental trial in an animal model.
AB  - Complete embolization of tumor tissue together with surrounding liver
      sufficiently prevents collateral blood supply to the tumor, offering curative
      treatment for hepatic malignancies. The present experiment was designed to test
      the feasibility of hepatic lobar ablation by means of the transcatheter
      chemoembolization technique. Five groups of rats (n = 6) were treated with a
      mixture of iodized oil/ethanol in ratios of 5:1, 4:1, 3:1, 1:1, and 1:0, which
      was injected selectively into the right-lobe artery until saturation during open
      surgery. Another group (n = 6) was studied using in vivo microscopy to observe
      the distribution of the mixture in the liver and changes in hepatic
      microcirculation. Ethiodol/ethanol mixture entered the portal vein after
      injection into the hepatic artery creating dual, complete arterial and portal
      venous embolization. Lobar ablation effects were achieved in 2 weeks in the 5:1,
      4:1, and 3:1 ratio groups, indicated by the lobe/liver weight measurements (p <
      0.001 vs normal liver). Hepatic arterial administration of the Ethiodol/ethanol
      mixture creates dual hepatic arterial and portal venous embolization, achieving a
      lobar ablation effect.

PMID- 9265679
TI  - Tubercular epididymitis and orchitis: US patterns.
AB  - For several decades tuberculosis has been adequately under control in this
      country, but there has been recent concern that this disease might be coming back
      to the forefront, due to the influx of immigrants from developing countries where
      tuberculosis is still rampant. In the years to come we are expecting an increase
      in cases of genitourinary lesions of tubercular origin, a disease which had
      practically disappeared in the Western world. The aim of this pictorial essay is
      to provide an outline of the typical US images of tubercular epididymitis and
      orchitis.

PMID- 9265680
TI  - Imaging of obstructive azoospermia.
AB  - Obstructive azoospermia represents approximately 10 % of cases of male
      hypofertility. It is classified according to the volume of ejaculate. When the
      latter is normal a proximal obstruction is suspected. Scrotal sonography can help
      to detect dilation of the epididymal head when clinical findings are equivocal.
      Ejaculatory duct obstruction (EDO) is suspected when the volume of ejaculate is
      low. The use of transrectal ultrasonography (TRUS) plays a major role in the
      investigation of these patients, and endorectal MRI is a very useful adjunct in
      selected cases. The most common cause of EDO is congenital bilateral absence of
      vas deferens, which is now thought to be a genital form of cystic fibrosis in 80
      % of cases. Consequently, a definitive diagnosis must be made before any attempt
      at in vitro fertilization. TRUS accurately visualizes abnormalities of the caudal
      junction of the vas deferens and seminal vesicles, yielding a definitive
      diagnosis without scrototomy. Other causes of EDO are congenital cysts
      compressing the distal part of the ejaculatory ducts and inflammatory distal
      stenosis. The former are accurately identified by TRUS, but the latter give more
      or less marked signs of obstruction which are only of value in azoospermic
      patients with a low-volume ejaculate. More invasive imaging is required to
      diagnose partial obstruction of the ED. Surgical vasography is still the
      reference, but puncture of the seminal vesicles under TRUS guidance is an
      attractive alternative, as it permits aspiration of seminal fluid (to seek motile
      sperm) and vasography without scrototomy. Lastly, endorectal MRI well assesses
      the relationships between the proximal prostatic urethra and the posterior wall
      of the ejaculatory ducts, which need to be precisely known when endoscopic
      resection of the ejaculatory ducts is planned.

PMID- 9265681
TI  - Image interpretation in CT of laryngeal carcinoma: a study on intra- and
      interobserver reproducibility.
AB  - The object of our study was to evaluate the intra- and interobserver
      reproducibility of the interpretation of CT examinations of laryngeal carcinoma.
      The CT examinations of 100 laryngeal cancers were retrospectively reviewed twice
      by two independent reviewers. Involvement of different structures was assessed,
      using a standard scoring form. Statistical analysis was done using the Wilcoxon
      signed rank test and Cohen's kappa. A borderline significant difference between
      the observers (p < 0.04) was present. Fair to substantial intraobserver
      reproducibility (kappa = 0.29-0.86), and fair to substantial interobserver
      reproducibility (average kappa = 0. 26-0.74) were found for most laryngeal
      structures when a dichotomous categorical scale was used. On the average somewhat
      lower, but still fair to substantial, intraobserver (kappa = 0.36-0.72), and fair
      to moderate interobserver (average kappa = 0.29-0.47) reproducibility, were found
      when a nominal or ordinal categorical scale was used. In conclusion, the
      interpretation of CT images of laryngeal tumors is reproducible.

PMID- 9265682
TI  - CNS involvement in AIDS: spectrum of CT and MR findings.
AB  - The brain may be affected by a variety of abnormalities in association with human
      immunodeficiency virus (HIV) infection. Knowledge of their existence and
      characteristic imaging features are important to radiologists for detection,
      diagnosis, and initiation of an appropriate treatment. Although there is a
      considerable overlap in the imaging characteristics of different entities, some
      findings are found to be very suggestive of a particular disease. The CT and MR
      imaging techniques are commonly used in the diagnosis of neurological disorders
      in acquired immunodeficiency syndrome (AIDS) patients, to verify treatment
      response and to guide brain biopsy. This review attempts to describe CT and MR
      features of infectious and malignant brain disorders in HIV-seropositive
      patients.

PMID- 9265683
TI  - Magnetic resonance imaging of posterior pituitary for evaluation of the
      neurohypophyseal function in idiopathic and autosomal dominant neurohypophyseal
      diabetes insipidus.
AB  - We investigated the role of MR imaging for evaluation of the functional status of
      the neurohypophyseal system in both idiopathic central diabetes insipidus (DI)
      and familial autosomal dominant neurohypophyseal DI. The patients and family with
      DI were analyzed retrospectively for the presence or absence of posterior
      pituitary gland hyperintense signal on MR images. A total of 19 adult patients
      with idiopathic central DI, 7 members of a family with autosomal dominant DI and
      20 control subjects were included in the study. Diagnosis of idiopathic DI was
      based on the presence of central DI in the absence of any alteration that is
      known to be responsible for DI. The patients were studied retrospectively and the
      morphology and intensity of the posterior lobe by MR imaging was assessed by
      blinded reading. In all patients with idiopathic central DI and the affected
      members of the family, the posterior bright signal was absent while the stalk was
      normal on MR images. In contrast, normal posterior pituitary bright signal and
      stalk were found in unaffected members of the family and all control subjects. We
      conclude that MR imaging of the posterior pituitary lobe can be used to evaluate
      the functional status of the neurohypophyseal system in idiopathic central DI and
      familial autosomal dominant DI.

PMID- 9265685
TI  - What is the value of the lateral chest radiograph in the follow-up thoracic
      lymphoma?
AB  - Lateral chest radiography in the investigation of thoracic lymphoma remains a
      feature of the current literature. This study assessed what information the
      lateral chest radiograph (CXR) adds in the follow-up of such patients. Eighty
      eight patients with known lymphoma who had a CXR and thoracic CT within the same
      4-week period were assessed. Five radiologists scored eight mediastinal and hilar
      nodal groups and eight extramediastinal regions on the frontal CXR as normal,
      equivocal or definitely abnormal (denoted 0, 1 and 2, respectively). This was
      repeated 1 week later with a combination of frontal and lateral films. Results
      were compared with the findings on CT which were scored similarly using accepted
      criteria for the presence of lymphadenopathy. Where the lateral CXR caused a
      change in score at any site, this change was compared with CT to determine the
      effect on diagnostic accuracy. For four of the five observers, the lateral film
      made no significant difference in diagnostic accuracy in the assessment of
      mediastinal lymph nodes. A fifth observer derived a small benefit from the
      addition of the lateral film, although almost 30 % of this was accounted for by
      changing from a wrong to an equivocal diagnosis. The lateral film did cause a
      small increase in the detection of pleuro-parenchymal lung lesions, although none
      of these were clinically significant. We conclude that routine lateral chest
      radiography is unhelpful in the follow-up of patients with lymphoma.

PMID- 9265684
TI  - Radiolabeled somatostatin analog scintigraphy in oncology and immune diseases: an
      overview.
AB  - [111In-DTPA-D-Phe1]-octreotide is a new radiopharmaceutical with a great
      potential for the visualization of somatostatin receptor-positive tumors,
      granulomas, and diseases in which activated leukocytes play a role. The overall
      sensitivity of [111In-DTPA-D-Phe1]-octreotide scintigraphy to localize
      neuroendocrine tumors is high. In several neuroendocrine tumor types, inclusion
      of somatostatin receptor imaging in the localization or staging procedure may be
      very rewarding, either in terms of cost-effectiveness, patient management, or
      quality of life. In our opinion, this holds true for patients with carcinoids,
      gastrinomas, paragangliomas, small-cell lung carcinoma, and selected cases of
      patients with insulinomas. The value of [111In-DTPA-D-Phe1]-octreotide
      scintigraphy in patients with other tumors, such as breast cancer, malignant
      lymphomas, or in patients with granulomatous diseases, has to be established.

PMID- 9265686
TI  - Magnetic resonance imaging findings of a nonfunctional mediastinal paraganglioma
      with an unusual presentation.
AB  - A case of histologically proven mediastinal paraganglioma presenting with
      metastatic spread to supraclavicular lymph nodes is presented. Mediastinal
      paragangliomas are extremely rare tumors and their CT and MR imaging features
      have not been well documented in the radiologic literature. The T 1-weighted and
      T 2-weighted spin-echo MR findings of a locally invasive mediastinal
      paraganglioma with metastasis to the supraclavicular lymph nodes are described
      and the literature is briefly reviewed.

PMID- 9265687
TI  - Added copper filtration in digital paediatric double-contrast colon examinations:
      effects on radiation dose and image quality.
AB  - Paediatric double-contrast barium enema examinations are usually performed at
      high tube voltage, 102-105 kV. The aim of this study was to investigate how much
      the effective dose to the child could be reduced by increasing the X-ray energy
      further by adding copper filter in the beam, and if this dose reduction could be
      achieved without endangering image quality. Organ doses to an anthropomorphic
      phantom simulating a 1-year-old child was measured using thermoluminescence
      dosimetry for assessment of the effective dose and this value was compared with
      the energy imparted which was obtained from kerma-area product measurements. To
      verify that the image quality achieved with this added filtration was still
      diagnostically acceptable, the study included 15 patient examinations. Since the
      increased X-ray energy will most probably affect low-contrast objects, image
      quality was also evaluated with two different phantoms containing low-contrast
      objects. Effective dose for a complete examination can be decreased 44 % and
      energy imparted 77 % when a 0.3-mm copper filter is inserted in the beam at tube
      voltage 102 kV. The patient study did not show any significant deterioration of
      image quality, whereas phantom measurements of contrast-detail resolution and
      signal-to-noise ratio was marginally impaired by the added copper filtration.
      This technique is now in clinical practice for paediatric colon examinations.

PMID- 9265688
TI  - Computed tomography with iodine-free contrast media.
AB  - The purpose of this work was to evaluate the enhancement of different
      concentrations of gadolinium (Gd), ytterbium (Yb) and iodine in vitro and in
      vivo. Comparisons were made of the enhancement (HU) of Gd, Yb and iodine in
      concentrations ranging from 0.1 to 30 mg/ml. In vivo dynamic CT studies were
      performed in ten dogs with 0.5 M Gd, Yb and iodine. Time-density curves were
      achieved in aorta and liver. The in vitro studies confirmed a decrease in the
      enhancement in this order: Gd (120 kV) > Gd (137 kV) > Yb (120 kV) > Yb (137 kV)
      > iodine (120 kV) > iodine (137 kV). The specific enhancement of Gd was 40.8 (120
      kV), of Yb 34.2 and of iodine 29.6 HU. The enhancement of the liver decreases
      from 21 HU (Gd) to 19 HU (Yb) and 12 HU (iodine). Gd and Yb achieved a higher
      aortal enhancement than iodine (190 vs 157 HU) All contrast media were well
      tolerated. Equimolar concentrations of Gd and Yb show a higher in vitro contrast
      and enhancement than iodine.

PMID- 9265689
TI  - Effective doses to members of the public from the diagnostic application of
      ionizing radiation in Germany.
AB  - The exposure of the German population to man-made radiation results mainly from
      diagnostic X-ray and nuclear medical examinations. Data are presented about the
      annual frequency and the average dose of the various examination types for West
      Germany in the years 1990-1992. According to these data a yearly average of
      approximately 1550 diagnostic examinations using ionizing radiation were
      performed per 1000 inhabitants resulting in an annual per caput effective dose of
      1.9 mSv. Despite the frequent use of alternative examination techniques, such as
      sonography, nuclear magnetic resonance and endoscopy, the frequency of X-ray and
      nuclear medical examinations is still increasing. If collective risk assessments
      are done using the per caput effective dose, at least the age distribution of the
      patients must be considered. This leads to a "risk-modifying factor" of 0.6-0.7
      for patients to be applied to the ICRP risk coefficient of 5 % per Sv valid for
      the general population. However, radiation risk must always be viewed in context
      with disease- and therapy-related risks and balanced against the benefit of the
      diagnostic examination, which should always exceed the risk for a well-indicated
      procedure.

PMID- 9265690
TI  - New technological developments in radiology: a challenge to preserving the
      specialty in Turkey.

PMID- 9265691
TI  - Central pontine myelinolysis: CT technique.

PMID- 9265692
TI  - Using hypertext and the Internet for structure and management of observational
      studies.
AB  - The evolution of computer and communications systems in the past decade brings
      new opportunities for increased efficiency and accuracy of observational studies.
      In ongoing, large scale research studies, the problem of bridging organizational
      and analytical methods of the past to modern methods of data structure and
      control can consume considerable effort. A model for information flow in an
      observational study is sketched, and the flow is found inherently complex. This
      complexity and corresponding managerial demands are compounded by database file
      proliferation and by evolution of system hardware and software. Interactive,
      network-based database mapping and documentation tools are described as currently
      implemented in an SAS-based system for the management and analysis of several
      large epidemiologic studies.

PMID- 9265694
TI  - Interpretation of the odds ratio from logistic regression after a transformation
      of the covariate vector.
AB  - Logistic regression assumes a linear relationship between the logit and the
      continuous covariate. When the relationship is not linear, one can employ
      transformations of the covariate to satisfy the linearity assumption. We present
      an approach that allows interpretation of the odds ratio as it relates to the
      continuous covariate in its original metric. A numerical example illustrates the
      results.

PMID- 9265693
TI  - Two-part survival models applied to administrative data for determining rate of
      and predictors for maternal-child transmission of HIV.
AB  - In analysing maternal-child HIV transmission from Medicaid claims data, we must
      deal with follow-up that is sometimes so short that we cannot claim that an
      apparently uninfected infant is actually uninfected as opposed to not yet
      exhibiting HIV-associated symptoms. To overcome this, we have been using analyses
      of 'time-to-diagnosis' of HIV infection to estimate transmission rates and
      predictors of transmission. Such analyses mix the event of transmission with that
      of our ability to diagnose HIV infection from coded claims data. We would like to
      separate these two pieces. Also, due to incomplete follow-up, Kaplan-Meier
      analyses will underestimate transmission rates. In econometrics and biostatistics
      there are two-part (mixture) models that can serve the goal of separating
      transmission from the process of diagnosing HIV infection in the newborn.
      Farewell describes a model that combines a logistic regression for the yes/no
      event (in our case, HIV transmission) and a Weibull regression model for the
      survival analysis portion (in our case, time-to-diagnosis). We use this approach
      to fit models that have potentially separate covariates for transmission and for
      time-to-diagnosis. The results allow us to identify predictors of transmission
      and estimate transmission rates with reduced concern for adequacy of follow-up.

PMID- 9265695
TI  - Derivation of the linear-logistic model and Cox's proportional hazard model from
      a canonical system description.
AB  - The linear-logistic regression model and Cox's proportional hazard model are
      widely used in epidemiology. Their successful application leaves no doubt that
      they are accurate reflections of observed disease processes and their associated
      risks or incidence rates. In spite of their prominence, it is not a priori
      evident why these models work. This article presents a derivation of the two
      models from the framework of canonical modeling. It begins with a general
      description of the dynamics between risk sources and disease development,
      formulates this description in the canonical representation of an S-system, and
      shows how the linear-logistic model and Cox's proportional hazard model follow
      naturally from this representation. The article interprets the model parameters
      in terms of epidemiological concepts as well as in terms of general systems
      theory and explains the assumptions and limitations generally accepted in the
      application of these epidemiological models.

PMID- 9265696
TI  - Designing and analysing case-control studies to exploit independence of genotype
      and exposure.
AB  - Genetic susceptibility and environmental exposures play a synergistic role in the
      aetiology of many diseases. We consider a case-control study of a rare disease in
      relation to a categorical exposure and a genetic factor under the assumption that
      the genotype and the exposure occur independently in the population under study.
      Using a logistic model for risk, we describe maximum likelihood methods based on
      log-linear models that explicitly impose the independence assumption, something
      the usual logistic regression analyses cannot do. The estimator of the genotype
      exposure interaction effect depends only on data from cases. Estimators for
      genotype and for exposure effects depend also no data from controls, but only
      through their respective marginal totals. All three estimators have smaller
      variance than they would were independence not enforced. These results have
      important implications for design: (i) Case-only studies can efficiently estimate
      gene-by-environment interactions. (ii) Studies where controls are genotyped
      anonymously can estimate genotype, exposure, and interaction effects as
      efficiently as designs where genotype and exposure data are linked. This feature
      addresses a growing concern of human subjects review boards. (iii) Exposure and
      interaction effects, but not genotype effects, can be estimated from studies
      where genetic information is only collected from cases (although one can recover
      the genotype effect if external gene prevalence data exist). Such designs have
      the compensatory benefit that the response rate (hence, validity) is higher when
      controls are not subjected to intrusive tissue sampling. However, the
      independence assumption can be checked only with linked genotype and exposure
      data for some controls. We illustrate the methods by applying them to recent
      study of cleft palate in relation to maternal cigarette smoking and to a variant
      of the transforming growth factor alpha gene in the child.

PMID- 9265697
TI  - Reparametrization of autoregressive models with coefficients depending on
      covariables: application to EEG spectrum maturation.
AB  - To describe the spectral characteristics of the EGG development through
      autoregressive (AR) time series models it is necessary to perform regression
      analysis of the AR parameters with regards to the age of the subject. A major
      difficulty in this approach is the very complex nature of the admissible region
      of the AR coefficients, which impedes the straight use of regression techniques.
      The present paper overcomes this difficulty by first applying the Barndoff
      Nielsen and Schou reparametrization of AR models, followed by Fisher's
      transformation and then carrying out age regression analysis of the transformed
      parameters. We apply this approach to real EEG data obtained from a normative
      sample of subjects in the age range from 5 to 95 years.

PMID- 9265698
TI  - The merits of matching in community intervention trials: a cautionary tale.
AB  - Concern about potential imbalance on risk factors in community intervention
      trials often prompts researchers to adopt a pair-matched design in which similar
      clusters of individuals are paired and one member of each matched pair is then
      randomly assigned to the intervention group. It is known that if there are few
      clusters in trial, it becomes increasingly difficult to obtain close matches on
      all potential risk factors. One may thus offset any gain in precision with loss
      in degrees of freedom due to matching. We shown in this paper that there are also
      several analytic limitations with pair-matched designs. These include: the
      restriction of prediction models to cluster-level baseline risk factors (for
      example, cluster size), the inability to test for homogeneity of odds ratios, and
      difficulties in estimating the intracluster correlation coefficient. These
      limitations lead us to present arguments that favour stratified designs in which
      there are more than two clusters in each stratum.

PMID- 9265699
TI  - Testing homogeneity of intra-run variance parameters in immunoassay.
AB  - A common assumption in the analysis of immunoassay data is a similar pattern of
      within-run variation across runs of the assays. One makes this assumption without
      formal investigation of its validity, despite the widely acknowledged fact that
      accurate understanding of intra-run variation is critical to reliable calibration
      inference. We propose a simple procedure for a formal test of the assumption of
      the homogeneity of parameters that characterize intra-run variation based on
      representation of standard curve data from multiple assay runs by a non-linear
      mixed effects model. We examine the performance of the procedure and investigate
      the robustness of calibration inference to incorrect assumptions about the
      pattern of intra-run variation.

PMID- 9265700
TI  - Exact equivalence test for risk ratio and its sample size determination under
      inverse sampling.
AB  - When data are dichotomous, this paper notes the utility of inverse sampling in
      establishing equivalence with respect to the risk ratio. This paper develops an
      exact equivalence test that accounts for the risk ratio under inverse sampling
      and further discusses the relationship between the exact equivalence test and the
      exact conditional confidence limits. Also included are an exact and two
      asymptotic procedures for calculation of the minimum required number of index
      subjects for a desired power 1--beta at a given alpha-level. Finally, this paper
      provides a table that summarizes the minimum required number of index subjects
      for powers equal to 0.90 and 0.80 in application of the proposed exact
      equivalence test at 0.05-level in a variety of situations.

PMID- 9265701
TI  - Vitreous Hemorrhage.
AB  - The incidence of spontaneous vitreous hemorrhage is approximately 7 cases per
      100,000 population. Proliferative diabetic retinopathy (32%), retinal tear (30%),
      proliferative retinopathy after retinal vein occlusion (11%) and posterior
      vitreous detachment without retinal tear (8%) are the most common causes of
      spontaneous vitreous hemorrhage. Vitreous hemorrhage can be caused by the
      pathologic mechanisms of disruption of normal retinal vessels, bleeding from
      diseased retinal vessels or abnormal new vessels, and extension of hemorrhage
      through the retina from other sources. Hemorrhage into the vitreous gel results
      in rapid clot formation and is followed by slow clearance of approximately 1% per
      day. The cellular response to vitreous hemorrhage is unusual with regard to
      hemorrhage in any tissue outside the vitreous cavity and has been compared to a
      "low-turnover" granuloma. Unique clinicopathologic features of long-standing
      vitreous hemorrhage include cholesterolosis bulbi (synchysis scintillans),
      hemoglobin spherulosis, and vitreous cylinders. Complications of nonclearing
      vitreous hemorrhage are hemosiderosis bulbi and glaucoma. Ghost cell glaucoma,
      hemolytic glaucoma, and hemosiderotic glaucoma may result from vitreous
      hemorrhage. The established treatment option for nonclearing vitreous hemorrhage
      is pars plana vitrectomy. Experimental nonsurgical treatment options involve
      improvement of physiologic clearance mechanisms in order to accelerate
      fibrinolysis, liquefaction, hemolysis and phagocytosis.

PMID- 9265702
TI  - Iris fluorescein angiography in clinical practice.
AB  - Iris fluorescein angiography is a valuable technique for elucidating a wide range
      of eye pathologies, among them developmental anomalies, degenerative disease,
      retinal vascular occlusions, diabetic microangiopathy, uveitis of various
      etiologies, glaucoma, tumor, and surgical or accidental trauma. In fact, IFA is
      more sensitive than biomicroscopy in the evaluation of iris abnormalities.
      Moreover, it provides indirect but reliable information on the retinal
      circulation when this cannot be examined directly. Some of the most important
      clinical applications involve the early detection of iris new vessels, cataract
      management in diabetic patients, and monitoring of iris tumors. Equipment,
      procedures, and fluorescein angiography patterns in normal and disease states are
      described and extensively illustrated. More widespread use of this valuable
      technique is encouraged.

PMID- 9265703
TI  - Nitric oxide in the eye: multifaceted roles and diverse outcomes.
AB  - Recent works have highlighted the role of nitric oxide in a wide array of disease
      entities, including septic shock, hypertension, cerebral ischemia, and chronic
      degenerative diseases of the nervous system. The functions of nitric oxide appear
      very diverse, having actions on vascular tone, neurotransmission, immune
      cytotoxicity, and many others. Nitric oxide is an important mediator of
      homeostatic processes in the eye, such as regulation of aqueous humor dynamics,
      retinal neurotransmission and phototransduction. Changes in its generation or
      actions could contribute to pathological states such as inflammatory diseases
      (uveitis, retinitis) or degenerative diseases (glaucoma, retinal degeneration).
      Localization in the eye and biochemical characteristics of nitric oxide will be
      reviewed. A better understanding of the nitric oxide pathway will be the key to
      the development of new approaches to the management and treatment of various
      ocular diseases.

PMID- 9265704
TI  - Informed consent: putting risks into perspective.
AB  - It is difficult, if not impossible, for patients to understand the significance
      of the involved risks when they are asked to sign informed consent prior to a
      procedure. Although practitioners seek to be diligent in discussing the
      significant, albeit remote, risks and benefits of accepting a recommended
      procedure, risks are usually addressed only in vague terms that may seem
      irrelevant to the patient. We offer a simple method whereby risk of an untoward
      event occurring during an ophthalmic procedure is compared with risks involved in
      daily activity. The Paling Perspective Scale allows better communication of risks
      between the physician and the patient, and reduces the likelihood of subsequent
      litigation.

PMID- 9265705
TI  - Discovering a dys-covering lid.
AB  - A patient with a large pituitary adenoma presenting with signs of primary
      aberrant regeneration of the left oculomotor nerve is reported. The proposed
      pathophysiological mechanisms involved in this syndrome are discussed and the
      known lesions causing it are listed. The various presentations of a pituitary
      adenoma, common and less common, are reviewed. Although neuroimaging is readily
      available, predicting the site of the lesion based on a meticulous clinical
      examination remains a challenge for ophthalmologists.

PMID- 9265707
TI  - Maximising the potential of practice.

PMID- 9265706
TI  - Optical explanation of the gradual disappearance of flying dots in posterior
      vitreous detachment.
AB  - It is well-known that flying dots (muscae volitantes) in posterior vitreous
      detachment gradually disappear. An analogy for this phenomenon is the optical
      effect of planets casting conic shadows as they are lighted by the sun (in this
      case the pupil serves as the light source) and these shadows shrink as the
      planets near the sun. When the opacities move forward in the vitreous cavity,
      their shadows are not long enough to reach the retina, so the flying dots
      disappear. They can also disappear when their shadows fall on the optic disk or
      when they are mixed with the random pattern of bright and dark areas of the
      retinal image in ordinary conditions. Pupil dilatation makes the conoid shadow
      shorter; thus, the flying dots became fainter. In advanced cataract, stray light
      makes the retinal image less sharp, reducing the perception of dots. Replacement
      of the opacified lens by an intraocular lens restores the sharpness of the
      retinal image, because the light entering the eye becomes less diffuse, making
      the flying dots more obvious. The same reasoning explains similar phenomena in
      aphakia and large ametropias with and without corrective spectacles, as well as
      opacities of any etiology in the vitreous.

PMID- 9265708
TI  - Nematode control practices and anthelmintic resistance on British sheep farms.
AB  - Nearly 23 per cent of 3000 randomly selected sheep farmers returned
      questionnaires on strategies to control the development of anthelmintic
      resistance. Twenty-five per cent stated that they regularly checked the accuracy
      of their drenching gun, and 52 per cent stated that they weighed a few animals
      and treated the whole flock like the heaviest. The mean annual frequency of
      dosing lambs was 4.39 compared with 2.43 for ewes. Forty-eight per cent stated
      that they changed the anthelmintic group annually. Seventeen per cent always
      treated sheep brought on to their farm with ivermectin. However, only 7 per cent
      had had their flocks tested for anthelmintic-resistant nematodes. The responses
      suggest that most sheep farmers are not actively seeking to prevent the
      development and spread of anthelmintic-resistant nematodes.

PMID- 9265709
TI  - Entanglement in fishing gear and other causes of death in cetaceans stranded on
      the coasts of England and Wales.
AB  - Between August 1990 and September 1995 the carcases of 422 cetaceans of 12
      species that had died around the coasts of England and Wales were examined. There
      were 234 harbour porpoises (Phocoena phocoena), 138 common dolphins (Delphinus
      delphis), and 50 individuals of 10 other species of dolphins and whales. The
      cause of death was diagnosed in the harbour porpoises and common dolphins was
      entanglement in fishing gear (bycatch). Of the cases in which the cause of death
      was established, 66 (38 per cent) of 176 harbour porpoises, 86 (80 percent) of
      108 common dolphins, and six (19 per cent) of 31 individuals of other species had
      been bycaught. Neonatal starvation, pneumonia and generalised infections
      accounted for a further 31 per cent of the diagnosed causes of death in harbour
      porpoises. The proportion of stranded common dolphins that had been bycaught was
      consistently high except during 1995, but the proportion of stranded harbour
      porpoises which had been bycaught increased in each successive year.

PMID- 9265710
TI  - Treatment of a dog with an insulinoma-related peripheral polyneuropathy with
      corticosteroids.
AB  - A crossbreed dog with a history of a chronic progressive tetraparesis had an
      insulinoma-related peripheral polyneuropathy. Frequent feeding and treatment with
      corticosteroids resulted in recovery from a non-ambulatory to an almost
      completely normal clinical state, despite the persistence of hypoglycaemia and
      hyperinsulinism. After euthanasia for uncontrollable seizures, the presence of a
      beta-cell carcinoma of the pancreas and extensive axonal degeneration of the
      peripheral nerves was confirmed by histopathological examination. These findings
      may indicate an immune-mediated pathogenesis for insulinoma-related peripheral
      polyneuropathy.

PMID- 9265711
TI  - Intrauterine infection with Ehrlichia phagocytophila in a cow.
AB  - An infection with Ehrlichia phagocytophila, the agent of tickborne fever, can
      cause abortion or stillbirth in cows in late pregnancy but, to the authors'
      knowledge, there have been no reports of intrauterine infection in cows followed
      by clinical signs in the calf. To study the effect of E phagocytophila on the
      fetus, a cow was infected experimentally after 270 days of pregnancy. It
      developed the clinical and haematological signs characteristic of tickborne fever
      six days after infection. At 287 days of pregnancy the cow gave birth to a live
      calf, which became ill at 13 days of age. The general condition and behaviour of
      the calf were only mildly affected but it had a high temperature and swollen
      prescapular lymph nodes. Its appetite and suck reflex remained normal. E
      phagocytophila inclusion bodies were visible, predominantly in neutrophils and
      eosinophils, for seven days. The calf seroconverted, as detected by indirect
      immunofluorescence, 14 days after it became ill.

PMID- 9265712
TI  - Prevalence of Lawsonia intracellularis in swine herds in Taiwan.

PMID- 9265713
TI  - Acute inhalant toxicoses of cagebirds.

PMID- 9265714
TI  - Virulent foot rot in sheep.

PMID- 9265715
TI  - Intrac vaccine: batch recall.

PMID- 9265716
TI  - Recall of Droplix.

PMID- 9265717
TI  - Clinical mastitis in dairy cows after 'blitz' therapy.

PMID- 9265718
TI  - [Comment on the contribution by Dr. A. Eckardt et al. "Psychological factors in
      therapy of lumbar intervertebral disk displacement"].

PMID- 9265719
TI  - Protein engineering from plants to animals, from big to small, from outside to
      inside and other advances.

PMID- 9265720
TI  - Stabilization of protein structures.
AB  - The technique of protein stabilization has been improving steadily in recent
      years, but it is only in the past year or two that the stability of some protein
      molecules has been improved to the level of those from extreme thermophilic
      organisms. This was achieved by multiple mutations and often by utilizing the
      knowledge gained from the homologous protein structures from extreme
      thermophiles.

PMID- 9265721
TI  - Engineering novel proteins by transfer of active sites to natural scaffolds.
AB  - Novel functional proteins have been generated by the transfer of active sites to
      structurally homologous proteins and to new structural contexts. The most
      successful examples of these approaches succeeded in providing effective new
      tools in biochemistry and protein chemistry and in suggesting new models in drug
      design.

PMID- 9265722
TI  - Therapeutic peptides and peptidomimetics.
AB  - Peptidomimetics are one set of probes used in the transition pathway of small
      molecule drug design. Cyclization of the peptide backbone and its modification
      with aromatic residues constitutes an effective approach to mimetic drug design
      and circumvents obstacles associated with delivery and formulation of peptides
      and peptidomimetics. In the past year, examples of mimicking beta-turn structures
      has led to combining design strategies with molecular libraries, demonstrating
      that peptidomimetics can provide valuable clues about receptor similarities not
      revealed by their endogenous ligands. This information can lead to the
      development of dual inhibitors. In addition, this work suggests that the use of
      libraries and rational design need not be mutually exclusive approaches to lead
      discovery.

PMID- 9265723
TI  - Design of peptide and polypeptide vaccines.
AB  - Advances have been made in the development of vaccines based on synthetic
      peptides and polypeptides representing tumor-associated antigens and protective
      epitopes of viruses and parasites. Advances within the past year include the
      design of vaccines based on artificial proteins, for example multiantigen
      peptides, branched polypeptides, fusion and recombinant peptides, as well as
      single T cell epitopes and tumor antigen peptides. Although peptide vaccines are
      not in use as yet, their potential is being explored.

PMID- 9265724
TI  - Engineering antibodies for imaging and therapy.
AB  - Several advances made during the past year will probably facilitate the
      development of therapeutic antibodies. Most notably, significant progress has
      been made in the rapid isolation of high affinity human antibodies from phage
      display libraries and by immunization of transgenic mice. The therapeutic
      potential of bispecific antibody fragments and Fc-containing proteins has been
      greatly enhanced by improved production methods. The utility of radiolabeled
      antibody fragments has been improved by the development of site-specific labeling
      methods and by the advent of the 'minibody', an engineered fragment that has
      proved to be highly successful for tumor imaging in mice.

PMID- 9265726
TI  - The state of antibody catalysis.
AB  - One of the fascinations of catalytic antibodies is the possibility of harnessing
      the mechanisms available to enzymes for chemical transformation and applying them
      to the broad realm of chemistry encountered in organic synthesis. Recently, the
      catalytic repertoire of antibodies has been extended to include mechanistically
      more complex bimolecular reactions and the immunological response to the hapten
      can be more thoroughly examined as a result of the advent of new screening
      technology using bacterial phages or auxotrophic cell lines.

PMID- 9265725
TI  - Production of human antibody repertoires in transgenic mice.
AB  - Transgenic mice have been created that carry human immunoglobulin heavy and light
      chain genes in germline configuration and that have the corresponding endogenous
      genes silenced. The transgenes are either minigene constructs or large, almost
      authentic, transloci on yeast artificial chromosomes and undergo B-cell-specific
      DNA rearrangement and hypermutation in the mouse lymphoid tissue. Monoclonal
      antibodies with good affinities for human antigens have been obtained after
      immunisation. These mice may be a future source of human antibodies for therapy.

PMID- 9265727
TI  - Transcription factors in immune-mediated disease.
AB  - A large amount of detailed information about the intracellular proteins
      regulating NF-kappa B activation and the cellular response to NF-kappa B
      activation has emerged recently. Several small molecules, an antisense
      oligonucleotide, and gene therapeutic agents that inhibit NF-kappa b activation
      have been described. Despite this, there are still significant gaps in our
      understanding of this process and its consequences. In contrast, the
      characterization of transcription factors selectively regulating cytokine
      production by CD4+ T cell subsets is at a very early stage. Three interacting
      proteins have recently been shown to contribute to subset-restricted expression
      of the IL-4 gene. There are other elements regulating IL-4 gene expression,
      however, and the relative importance of these recently identified proteins has
      yet to be determined.

PMID- 9265728
TI  - Chimeric receptors as gene switches.
AB  - There is a recognized need for eukaryotic molecular gene switches that are
      tightly regulated by the administration of small molecule drugs. The modular
      nature of intracellular receptor proteins has allowed the recent development of
      chimeric receptors that fulfill this need. These switches will help dissect the
      roles that specific proteins play in signaling pathways, cell differentiation and
      development. Some of these switches will also be used in gene therapy to regulate
      therapeutic gene expression.

PMID- 9265729
TI  - Structural aspects of heterotrimeric G-protein signaling.
AB  - Recently, structures of heterotrimeric G-protein subunits have been determined in
      isolation, in conjunction with each other, and in complex with their regulators.
      Along with biochemical information, these structures suggest how G-protein
      subunits are oriented relative to the membrane surface and relative to seven
      transmembrane helix receptors. They also suggest mechanisms for receptor
      catalyzed nucleotide exchange.

PMID- 9265730
TI  - Rapid, sensitive sequencing of oligosaccharides from glycoproteins.
AB  - The release of sub-picomole levels of N-linked oligosaccharides directly from 1-5
      micrograms of protein in a band on an SDS PAGE gel, coupled with recent advances
      in mass spectrometry and HPLC, opens the way for the analysis of biologically
      important glycoproteins that are difficult to purify or are available only in
      limited amounts. A straightforward HPLC strategy enables the structures of both
      neutral and sialylated components of the N-glycan pool to be predicted from a
      single run. The entire pool of sugars may then be sequenced simultaneously, using
      exoglycosidase arrays.

PMID- 9265731
TI  - Reliable determination of binding affinity and kinetics using surface plasmon
      resonance biosensors.
AB  - Progress has been made in the identification of experimental and analytical
      procedures that allow for a more reliable determination of equilibrium and
      kinetic constants. Possible origins of the frequently observed deviations of the
      measured binding progress from that expected for chemical binding of pseudo-first
      order, and appropriate experimental controls have been proposed. Improved
      analytical approaches include the application of global analysis and analytical
      corrections for the influence of mass transport.

PMID- 9265732
TI  - Phage display of combinatorial antibody libraries.
AB  - The selection of antibodies from combinatorial libraries displayed on the surface
      of filamentous phage has become an important methodology for the generation of
      reagent, diagnostic, and therapeutic molecules and for the study of natural
      immune responses. Using this technique, antibody genes have been cloned from
      multiple species or expressed directly from large man-made repertoires of
      antibody-encoding genes. Recent studies demonstrate that the technique allows for
      the in vitro evolution of antibodies to create molecules whose affinity for
      antigen exceeds that observed in nature.

PMID- 9265733
TI  - Protein engineering.

PMID- 9265734
TI  - Variation in transformation frequencies among six common wheat cultivars through
      particle bombardment of scutellar tissues.
AB  - The transformation technique in common wheat has already been established by
      using microprojectile bombardment and scutellar tissues of immature embryos. In
      this study, in vitro culture response of immature embryos and the production of
      transgenic wheat plants were examined in six common wheat cultivars, i.e.,
      Chinese Spring, Akadaruma, Haruhikari, Shiroganekomugi, Norin 12, and Norin 61.
      In all genotypes, more than seven hundred immature embryos were bombarded with a
      plasmid containing a bialaphos-resistant gene under control of the rice actin 1
      gene. (Act1) promoter. Although the transient expression of the reporter gene
      encoding beta-glucuronidase following the rice Act1 promoter was similar in five
      of the six cultivars tested, the frequency of stable transformation varied with
      the genotype. The frequency of transformation was the highest in Akadaruma and
      Norin 12 of the six wheat cultivars; independently transformed plants were
      produced from 1.4% and 1.7% of bombarded embryos, respectively. On the other
      hand, the immature embryos of Norin 61 and Shiroganekomugi showing low efficiency
      of in vitro culture generated no transgenic plants. This variation of the
      transformation frequency was generally caused by the difference in the in vitro
      culture response with the genotype, rather than the efficiency of the
      introduction of the transgene into wheat cells by particle bombardment.

PMID- 9265735
TI  - Mitochondrial DNA differentiation in the Japanese brown frog Rana japonica as
      revealed by restriction endonuclease analysis.
AB  - To elucidate mtDNA differentiation in the Japanese brown frog Rana japonica, and
      compare it with results from allozyme analysis and crossing experiments, RFLP
      analysis was conducted on 78 frogs from 16 populations in Honshu. Purified mtDNA
      was digested with eight six-base recognizing restriction enzymes and analyzed by
      1% agarose-slab gel electrophoresis. Cleavage patterns of the mtDNA showed three
      distinct genome size classes: small (18.5 kb), middle (20.0 kb) and large (21.5
      kb). Ten haplotypes (I approximately X) were observed among the 16 populations.
      The expected nucleotide divergences within populations ranged from 0 to 0.47%
      with a mean of 0.08%. The net nucleotide divergences among 16 populations ranged
      from 0 to 7.74% with a mean of 3.49%. The UPGMA dendrogram and NJ tree, which
      were constructed based on the net nucleotide divergences, showed that R. japonica
      diverged first into the eastern and western groups. The eastern group
      subsequently differentiated into a subgroup containing six populations and the
      Akita population, and the western group divided into several subgroups. These
      results, as well as the results of allozyme analysis and crossing experiments,
      suggest the the eastern and western groups have experienced secondary contact,
      and introgression has occurred in the Akita population.

PMID- 9265736
TI  - Roles of the recG gene product of Escherichia coli in recombination repair:
      effects of the delta recG mutation on cell division and chromosome partition.
AB  - The products of the recG and ruvAB genes of Escherichia coli are both thought to
      promote branch migration of Holliday recombination intermediates by their
      junction specific helicase activities in homologous recombination and
      recombination repair. To investigate the in vivo role of the recG gene, we
      examined the effects of a recG null mutation on cell division and chromosome
      partition. After UV irradiation at a low dose (5J/m2), delta recG mutant
      filamentous cells with unpartitioned chromosomes. A mutation in the sfiA gene,
      which encodes and SOS-inducible inhibitor of septum formation, partially
      suppressed filamentation of recG mutant cells, but did not prevent the formation
      of anucleate cells. The sensitivity of UV light and the cytological phenotypes
      after UV irradiation of a recA recG double mutant were similar to a recA single
      mutant, consistent with the role of recG, which is assigned to a later stage in
      recombinant repair than recA. The recG ruvAB and recG ruvC double mutants were
      more sensitive to UV, almost as sensitive as the recA mutant and showed more
      extreme phenotypes concerning filamentation and chromosome nondisjunction, both
      after UV irradiation and without UV irradiation than either recG or ruv single
      mutants. The recG polA12 (Ts) mutant, which is temperature sensitive in growth,
      formed filamentous cells with centrally located chromosome aggregates when grown
      at nonpermissive temperature similar to the UV irradiated recG mutant. These
      results support the notion that recG is involved in processing Holliday
      intermediates in recombination repair in vivo. We suggest that the defect in the
      processing in the recG mutant results in accumulation of nonpartitioned
      chromosomes, which are linked by Holliday junctions.

PMID- 9265737
TI  - Polyploid-specific repetitive DNA sequences from triploid ginbuna (Japanese
      silver crucian carp, Carassius auratus langsdorfi).
AB  - Repetitive DNA sequences (Cal3nDr) in the genome of a triploid ginbuna (Carassius
      auratus langsdorfi) were isolated from the DraI digests of the genomic DNA. This
      AT-rich (61%) Cal3nDr monomer was 137 bp in length. The nucleotide similarity
      among the monomers from the same individual was considerably high (above 97%).
      Hybridization analyses revealed that the Cal3nDr sequences were organized into
      tandem arrays. These DNA sequences were present only in triploid and tetraploid
      ginbunas and were absent from diploid ginbuna, gengorobuna, goldfish, and other
      cyprinid fishes, and therefore appeared to be specific to polyploid ginbunas. In
      situ hybridization data showed their localization on one to four out of a total
      of 150 to 156 chromosomes, depending on the individuals or clonal lines, of the
      triploid ginbuna. The origin of the Cal3nDr sequences is also discussed on the
      basis of observation of the artificial triploid ginbuna produced by crossing a
      diploid female with a tetraploid male.

PMID- 9265738
TI  - Molecular cloning and functional analysis of an rpoS homologue gene from Vibrio
      cholerae N86.
AB  - A homologue of the rpoS gene of Escherichia coli was cloned from Vibrio cholerae
      N86 by complementation of the phenotypes of the E. coli rpoS mutant strain. We
      determined the DNA sequence of this gene. Sequence alignments have indicated that
      the rpoS gene of V. cholerae N86 encoding a 39-kDa protein is very similar to
      that of E. coli. In addition, the nlpD-like gene was found in the upstream region
      of the rpoS gene in the same order as in E. coli. These results suggest that the
      organization of these genes is highly conserved between E. coli and V. cholerae.

PMID- 9265739
TI  - Chemicals and heat generate different protein patterns in Acinetobacter
      calcoaceticus.
AB  - The effect of exposing Acinetobacter calcoaceticus 69-V to DNP-stress and heat
      shock was examined by two-dimensional gel electrophoresis of proteins, which were
      detected either by autoradiography or by silver staining. Both DNP stress and
      heat shock led to altered patterns of protein synthesis or concentration. About
      10% of the proteins which were synthesized newly or at an increased rate and
      about 25% of those which were found newly or with an increased concentration
      after DNP treatment were identified after heat shock, too.

PMID- 9265740
TI  - Phenoxyacetic acid induces glutathione-dependent detoxification and depletes the
      glutathione pool in Penicillium chrysogenum.
AB  - Enzymes of the glutathione-dependent detoxification pathway (glutathione S
      transferase and gamma-glutamyl-transpeptidase) were induced, and the glutathione
      pool was completely depleted by phenoxyacetic acid in Penicillium chrysogenum
      mycelia incubated for 15 h in a culture medium containing lactose as a carbon
      source and sodium glutamate as a nitrogen source. A significant increase in both
      the oxidised glutathione concentrations and the glutathione reductase activities
      were also observed. 1-Chloro-2,4-dinitrobenzene--a potent substrate and inducer
      of glutathione S-transferase-initiated very similar physiological changes but no
      beta-lactam production could be detected in this case. When (NH4)2HPO4 was used
      as a nitrogen source the penicillin biosynthesis was repressed and the induction
      of gamma-glutamyltranspeptidase by phenoxyacetic acid was hindered considerably.

PMID- 9265741
TI  - Production of nisin-like bacteriocins by Lactococcus lactis strains isolated from
      vegetables.
AB  - Four bacteriocin producing lactic acid bacteria isolated from vegetables were
      identified as Lactococcus lactis strains on the basis of physiological and
      biochemical characteristics, carbohydrate fermentation patterns and analysis of
      total soluble protein pattern by SDS PAGE. The bacteriocins had a wide spectrum
      of activity as antagonism was detected not only towards a variety of lactic acid
      bacteria, but also to Staphylococcus aureus and Listeria monocytogenes. These
      bacteriocins were resistant to heating at 121 degree C for 15 minutes and showed
      highest activity at low pH (<5.0). They were inactivated by the proteolytic
      enzymes alpha-chymotrypsin and proteinase K, but not by lipase, alpha-amylase,
      catalase or lysozyme. These bacteriocinogenic Lactococcus strains were all immune
      to the bacteriocins produced as well as to commercial nisin. Bacteriocin producer
      culture supernatants showed a high degree (70 or 100%) of cross-reactivity in the
      nisin ELISA, suggesting similarity of the produced bacteriocins to nisin. The
      potential application of bacteriocin producing lactococci of vegetable origin for
      safety assurance of vegetable foods and controlling vegetable fermentations is
      discussed.

PMID- 9265742
TI  - Effect of certain nutrients on the production of dextransucrase from Leuconostoc
      mesenteroides NRRL B-512F.
AB  - The effects of certain nutrients on dextransucrase (sucrose: 1,6-alpha-d-glucan 6
      alpha-d-glucosyltransferase EC 2.4.1.5) production from Leuconostoc mesenteroides
      NRRL B-512F were studied. An increase in concentration of sucrose to 4% in the
      enzyme production medium resulted in the increase of activity of dextransucrase.
      Higher enzyme yields were obtained at low yeast extract and high phosphate
      concentrations. The presence of peptone and beef extract in the medium in
      addition to 2% yeast extract resulted in an enhanced production of
      dextransucrase. The enzyme activity increased by 30% by both peptone and beef
      extract. Addition of Tween 80 to the medium enhanced the production of enzyme and
      the activity was increased by 25%. Magnesium ions stimulated the activity
      marginally. Sodium fluoride enhanced the activity of dextransucrase by 25%.

PMID- 9265743
TI  - Degradation of dimeric lignin model compounds by aerobic bacteria isolated from
      the hindgut of xylophagous termites.
AB  - The capability of the intestinal flora from the gut of xylophagous termites of
      degrading lignin model compounds was investigated. Different dimeric lignin model
      compounds-degrading bacteria were obtained from the hindgut flora of Mastotermes
      darwiniensis Froggatt, Reticulitermes santonensis Feytaud, Nasutitermes nigriceps
      Haldeman and Zootermopsis angusticollis Hagen. In the presence of oxygen dimeric
      model compounds were degraded by all isolates. This indicates that the hindgut
      flora of termites is basically able to produce substrate for their host from
      aromatic extractives of wood.

PMID- 9265744
TI  - Heavy metal resistant Arthrobacter sp.--a tool for studying conjugational plasmid
      transfer between gram-negative and gram-positive bacteria.
AB  - The role of two heavy metal-resistant strains of the Gram-positive genus
      Arthrobacter sp. as a tool in studying conjugational plasmid transfer between
      Gram-positive and Gram-negative bacteria is described. The high nickel resistance
      and the cobalt resistance of Arthrobacter sp. strain RM1/6 could be transferred
      to Arthrobacter sp. strain WS14. IncQ plasmids (pKT240, pKT240::czc, pML10) could
      be mobilized from E. coli into Arthrobacter spp. strains; antibiotic (Km, Ap, Tc)
      and heavy metal (Co) resistance genes were expressed in the recipient stains.
      IncQ plasmid pKT240 could be mobilized between Arthrobacter spp. strains. IncP
      plasmid RP4::Tn4371 was transferred from A. eutrophus to Arthrobacter sp., RP4
      mediated antibiotic resistance to Km was expressed in the recipient strain.

PMID- 9265745
TI  - Active calcium ion transport Xenopus laevis skin.
AB  - The skin of intact, free-swimming Xenopus laevis transports Ca2+ inwardly in a
      manner that is proportional to the external [Ca2+] up to about 0.3 mmol.l-1,
      saturates above 0.3 mmol.l-1, and is opposed to the electrochemical gradient.
      Efflux is relatively constant at external concentrations between 0.016 and 0.6
      mmol.l-1; net flux which is negative below 0.125 mmol.l-1 becomes positive above
      this external [Ca2+]. Allometric analysis suggests that both Ca2+ influx and
      efflux scale to the 2/3 power approximately like surface area. There were no
      significant differences in influx between summer and fall animals; however,
      efflux was greater in the fall and this resulted in a change from positive
      balance in the summer to negative balance in the fall. Isolated skins were shown
      to support a Ca2+ uptake rate of nearly 30 nmol.cm-2.h-1. The phenylalkylamine
      verapamil in the apical bathing solution significantly inhibited this at 25
      mumol.l-1. The benzothiazepine diltiazem was also effective at 50 mumol.l-1 while
      the dihydropyradine nifedipine was ineffective up to 100 mumol.l-1. The inorganic
      ion La3+ was effective at blocking Ca2+ uptake at 300 mumol.l-1; Ni2+ was also
      effective at 500 mumol.l-1 but Co2+ was ineffective up to 500 mumol.l-1. These
      results suggest that apical calcium channels in Xenopus laevis skin have
      properties similar to mammalian L-channels and fish gill Ca2+ channels.

PMID- 9265746
TI  - Activity, blood temperature and brain temperature of free-ranging springbok.
AB  - We used miniature data loggers to record temperature and activity in free-ranging
      springbok (Antidorcas marsupialis) naturally exposed to severe nocturnal cold and
      moderate diurnal heat. The animals were active throughout the day and night, with
      short rests; the intensity of activity increased during daylight. Arterial blood
      temperature, averaged over many days, exhibited a circadian rhythm with amplitude
      < 1 degree C, but with a wide range which resulted from sporadic rapid deviations
      of body temperature. Peak blood temperature occurred after sunset. Environmental
      thermal loads had no detectable effect on blood temperature, even though globe
      temperature varied by > 10 degrees from day to day and > 20 degrees C within a
      day. Brain temperature increased approximately linearly with blood temperature
      but with a slope < 1, so that selective brain cooling tended to be activated at
      high body temperature, but without a precise threshold for the onset of brain
      cooling. Low activity attenuated selective brain cooling and high activity
      abolished it, even at high brain temperature. Our results support the concept
      that selective brain cooling serves to modulate thermoregulation rather than to
      protect the brain against heat injury.

PMID- 9265747
TI  - Role of peptide YY in regulation of duodenal motility during the interdigestive
      period in sheep.
AB  - Temporal coordination between duodenal migrating myoelectric complexes (MMC) and
      pancreatic exocrine secretion, and the effects of porcine peptide YY (PYY) on
      gastroduodenal motility and pancreatic exocrine secretion were examined during
      the interdigestive period in conscious mature sheep. Fluid and enzyme secretions
      from the exocrine pancreas showed a periodic pattern corresponding to the phases
      of duodenal MMC, although these secretion rates were maintained at a high level
      during phase II in sheep. Intravenous continuous infusion of PYY at doses ranging
      from 50 to 200 pmol.kg-1.h-1 or intravenous bolus infusion of PYY at doses
      ranging from 50 to 200 pmol.kg-1 showed a tendency to prolong the first cycle of
      the duodenal MMC and significantly shorten the second cycle. However, there was
      almost no effect on ruminal contractions from the PYY administration. In the
      pancreatic exocrine secretion, PYY could inhibit only bicarbonate secretion at
      only the highest dose of 200 pmol.kg-1. These results imply that endogenous PYY
      may play a physiological role in the regulation of the duodenal MMC cycles in
      sheep but not in ruminal contractions. PYY seems unlikely to regulate the
      pancreatic exocrine secretion in normal sheep, because a supraphysiological dose
      of PYY was required to inhibit the pancreatic exocrine secretion.

PMID- 9265748
TI  - Manganese metabolism is impaired in the Belgrade laboratory rat.
AB  - Homozygous Belgrade rats have a hypochromic anaemia due to impaired iron
      transport across the cell membrane of immature erythroid cells. This study aimed
      at investigating whether there are also abnormalities of Mn metabolism in
      erythroid and other types of cells. The experiments were performed with
      homozygous (b/b) and heterozygous (+/b) Belgrade rats and Wistar rats and
      included measurements of Mn uptake by reticulocytes in vitro, Mn absorption from
      in situ closed loops of the duodenum, and plasma clearance and uptake by several
      organs after intravenous injection of radioactive Mn bound to transferrin (Tf) or
      mixed with serum. Similar measurements were made with 59Fe-labelled Fe in several
      of the experiments. Mn uptake by reticulocytes and absorption from the duodenum
      was impaired in b/b rats compared with +/b or Wistar rats. The plasma clearance
      of Mn-Tf was much slower than Mn-serum, but both were faster than the clearance
      of Fe-Tf. Uptake of 54Mn by the kidneys, brain and femurs was less in b/b than
      Wistar or /+b rats, but uptake by the liver was greater in b/n rats. Similar
      differences were found for 59Fe uptake by kidneys, brain and femurs but is
      concluded that the genetic abnormality present in b/b rats affects Mn metabolism
      as well as Fe metabolism and that Mn and Fe share similar transport mechanisms in
      the cells of erythroid tissue, duodenal mucosa, kidney and blood-brain barrier.

PMID- 9265749
TI  - Milk composition and lactational output in the greater spear-nosed bat,
      phyllostomus hastatus.
AB  - Growth rates of mammalian young are closely linked to the ability of the mother
      to provide nutrients; thus, milk composition and yield provide a direct measure
      of maternal investment during lactation in many mammals. We studied changes in
      milk composition and output throughout lactation in a free-ranging population of
      the omnivorous bat, Phyllostomus hastatus. Fat and dry matter of milk increased
      from 9 to 21% and from 21 to 35% of wet mass, respectively, throughout lactation.
      Energy increased from 6 to 9 kJ.g-1 wet mass, primarily due to the increase in
      fat concentration. Total sugar levels decreased slightly but non-significantly.
      Mean sugar level was 4.0% of wet mass. Protein concentration increased from 6 to
      11% of wet mass at peak lactation and then decreased as pups approached weaning
      age. Total milk energy output until pups began to forage was 3609 kJ. Milk levels
      of Mg, Fe, Ca, K, and Na averaged 0.55 %/- 0.26, 0.23 +/- 0.2, 8.75 +/- 4.17,
      5.42 +/- 2.11, and 9.87 +/- 4.3 mg.g-1 dry matter, respectively. Of the minerals
      studied, calcium appears to be most limiting in this species. The high degree of
      variability in foraging time, milk composition and milk yield between individuals
      at the same stage of lactation could potentially yield high variance in
      reproductive success among females of this polygynous species.

PMID- 9265750
TI  - Focusing and imaging using eigenfunctions of the scattering operator.
AB  - An inverse scattering method that uses eigenfunctions of the scattering operator
      is presented. This approach provides a unified framework that encompasses
      eigenfunction methods of focusing and quantitative image reconstruction in
      arbitrary media. Scattered acoustic fields are described using a compact, normal
      operator. The eigenfunctions of this operator are shown to correspond to the far
      field patterns of source distributions that are directly proportional to the
      position-dependent contrast of a scattering object. Conversely, the
      eigenfunctions of the scattering operator specify incident-wave patterns that
      focus on these effective source distributions. These focusing properties are
      employed in a new inverse scattering method that represents unknown scattering
      media using products of numerically calculated fields of eigenfunctions. A
      regularized solution to the nonlinear inverse scattering problem is shown to
      result from combinations of these products, so that the products comprise a
      natural basis for efficient and accurate reconstructions of unknown
      inhomogeneities. The corresponding linearized problem is solved analytically,
      resulting in a simple formula for the low-pass-filtered scattering potential. The
      linear formula is analytically equivalent to known filtered-backpropagation
      formulas for Born inversion, and, at least in the case of small scattering
      objects, has advantages of computational simplicity and efficiency. A similarly
      efficient and simple formula is derived for the nonlinear problem in which the
      total acoustic pressure can be determined based on an estimate of the medium.
      Computational results illustrate focusing of eigenfunctions on discrete and
      distributed scattering media, quantitative imaging of inhomogeneous media using
      products of retransmitted eigenfunctions, inverse scattering in an inhomogeneous
      background medium, and reconstructions for data corrupted by noise.

PMID- 9265751
TI  - Effects of middle ear pressure on otoacoustic emission measures.
AB  - An animal surgical model was established to manipulate pressure in the middle
      ear. The 2 f1-f2 cochlear microphonic distortion product (CMDP) and distortion
      product otoacoustic emission (DPOAE) were simultaneously measured in order to
      analyze the effects of middle ear pressure on sound transmission. The frequency
      ratio of the two stimulus tones f2/f1 was held at 1.2 and the level ratio L1/L2
      was 10 dB. The effect of middle ear pressure on forward transmission was
      determined form the CMDP data. The effect on backward transmission was determined
      from the DPOAE data after the effect on forward transmission was subtracted out.
      The results showed a similar effect on forward and backward transmission. In
      general, negative pressure had a greater effect than positive pressure. Positive
      pressures of 10 and 20-cm H2O affected transmission for low-frequency stimuli (f2
      = 1620 and 2680 Hz) but had little effect for high-frequency stimuli (f2 = 6980
      and 10,250 Hz). Negative pressures of -2.5 to -10-cm H2O affected transmission
      across all frequencies tested. The effect at low frequencies is hypothesized to
      be related to tympanic membrane stiffness. The effect of negative pressure at
      high frequencies may be related to changes in the incudostapedial joint.

PMID- 9265752
TI  - Intermodulation components in inner hair cell and organ of Corti responses.
AB  - Two-tone responses are recorded from inner hair cells and from the organ of Corti
      fluid space in second and third turns of the guinea pig cochlea where best
      frequencies (BF) are approximately 4000 and 1000 Hz, respectively. This allows
      both ac and dc response components to be obtained and facilitates comparisons
      with psychophysical investigations that have traditionally been conducted at low
      and moderate frequencies. The measurements of ac responses in the organ of Corti
      fluid space also allow comparisons with mechanical results because the cochlear
      microphonic is proportional to basilar membrane displacement. By using a constant
      frequency ratio (f2/f1) of 1.4, local distortion products generated at the
      recording location are prominent when the two primaries are near the BF of the
      cell. However, when the primary pairs increase above BF, quadratic and cubic
      difference tones are recorded even when responses to the primaries are not
      measurable. The presence of these traveling distortion products is consistent
      with the idea that both f2-f1 and 2f1-f2 have their own traveling waves. Notches
      in the existence regions of quadratic and cubic difference tones were also
      observed and found to be influenced by mutual suppression between the two inputs.

PMID- 9265753
TI  - Otoacoustic emissions, hair cells, and myosin motors.
AB  - The stereovillar bundles of hair cells show active movements that may be
      generated by the putative myosin-actin interactions underlying hair-cell
      adaptation. Such movement is a possible candidate for the generation of
      spontaneous otoacoustic emissions (SOAE) in the ear canal of nonmammals. In the
      basilar papilla of certain lizard families, most hair cells are not coupled by a
      tectorial membrane, making it easier to assign the energy in emission peaks to
      defined groups of hair cells. We have studied 62 SOAE in the Bahamian Anole
      Anolis sagrei, which has about 140 hair cells with "free-standing" bundles in the
      high-frequency area of its papilla. Individual SOAE peaks were traced to between
      3 and 38 hair cells, and the mean power output per hair cell was calculated to be
      141 aW. The number of bundle myosins putatively involved in the generation of
      each SOAE was estimated and the force generated by each myosin at 1 kHz
      calculated to be approximately 0.1 pN. The data support the idea that hair cells
      generate emissions and suggest that myosin produces sufficient power to be the
      emission motor.

PMID- 9265754
TI  - The representation of concurrent vowels in the cat anesthetized ventral cochlear
      nucleus: evidence for a periodicity-tagged spectral representation.
AB  - Chopper units of the ventral cochlear nucleus (VCN) provide a rare representation
      of stimulus spectrum and a temporal representation of fundamental frequency (F0).
      This dual representation may be useful in segregating competing speech sounds,
      where differences in F0 are a cue. Responses to the vowel portion of concurrently
      presented pairs of syllables /bV integral/ with different F0's (88, 98, and 112
      Hz) were studied in the VCN of anesthetized cats; 11 English vowels were used for
      V. Vowels were chosen so that one had a formant frequency just above the unit's
      best frequency (BF) and the other had a formant just below BF. By changing the
      stimulus sampling rate, formant peaks were shifted relative to the unit's BF,
      producing a range of stimuli, varying in the relative power of the two vowels
      within the unit's tuning curve. Results show that units' discharge rates reflect
      the energy within their tuning curves and the relative synchronization of units'
      responses to the two F0's favors the dominant vowel. A method of segregating two
      vowels is provided in which relative synchronization to the F0's is used to
      apportion discharge rate between the vowels. Best results were obtained in
      chopper units, although primarylike units showed similar behavior.

PMID- 9265755
TI  - Two separate codes for missing-fundamental pitch in the human auditory cortex.
AB  - Two auditory event-related potential components, the supratemporal N1 and the
      mismatch negativity (MMN), index traces encoding the missing-fundamental pitch.
      The present results suggest that these two codes derive from separate pitch
      extraction processes. Frequent 300-Hz and infrequent 600-Hz missing-fundamental
      tones were presented, in some stimulus blocks with short (150 ms), in others,
      with long (500 ms) stimulus durations. MMN, reflecting a preattentive change
      detection process, was elicited by infrequent missing-fundamental tones only in
      the long-duration condition. Correspondingly, subjects were able to detect these
      high-pitch missing-fundamental tones amongst similar low-pitch ones only when the
      stimulus duration was long. In addition, the MMN response peaked ca. 120 ms later
      for missing-fundamental tones than for pure tones of the fundamental frequency
      suggesting that missing-fundamental pitch resolving took substantially longer
      than extracting the spectral pitch. In contrast, a differential N1 response to
      the missing-fundamental pitch was found for both stimulus durations, with no
      substantial difference in peak latency between the pure and missing-fundamental
      tones. The contrasting features found for the two auditory cortical missing
      fundamental pitch codes support the notion of two separate missing-fundamental
      pitch resolving mechanisms.

PMID- 9265757
TI  - Modulation detection interference with two-component masker modulators.
AB  - Thresholds were measured for detecting amplitude modulation of a single tonal
      carrier in the presence of modulated maskers. The masker modulator contained
      either one or two sinusoidal components. As found in previous studies, there was
      a detrimental effect of masker modulation on the detection of probe modulation.
      Interference was obtained with a 4-Hz separation between the two components of
      the masker modulator with the probe modulated at the 4-Hz beat rate. The amount
      of interference obtained with the two-component masker modulator was greater than
      that produced by the individual components of the masker modulator. The amount of
      interference increased with the depth of the masker-modulator beating and the
      number of masker carriers. The interference due to beating of the masker
      modulator components was reduced when the beat rate was increased from 4 to 10
      Hz. Results obtained with two-component masker modulators indicate a masking
      effect not predicted by a spectral representation of the probe and masker
      envelopes.

PMID- 9265756
TI  - Multiband detection of energy fluctuations.
AB  - this study sought to characterize the integration of synchronous energy
      fluctuations across relatively independent spectral regions. The detection of
      four classes of signal was examined where each class of signal was associated
      with a change in energy over time. The four signal types were: (1) multicomponent
      tonal complexes, with each component centered in a narrow band of noise; (2)
      intensity increments in multiple narrow bands of noise; (3) intensity decrements
      in multiple narrow bands of noise; and (4) temporal gaps in multiple narrow bands
      of noise. Each signal type was examined in a separate experiment, although
      stimulus characteristics such as presentation level and frequency location were
      held constant. Experiment 1 confirmed that the detection of multitonal complexes
      masked by narrow bands of noise is linearly related to the square root of N,
      where N is the number of signal components. Experiment 2 extended this to show
      that, when the signal was an increment in the level of a noise band carrier,
      threshold continued to be a linear function of the square root of N, although
      threshold was about 2 dB higher than for a comparable tonal signal. Experiment 3
      indicated that the detection of a decrement in energy in one or more noise bands
      was relatively poorer in terms of absolute level changes than was the detection
      of an energy increment in the same stimulus. Examination of psychometric
      functions for decrement detection suggested that performance improved by less
      than the square root of N. Experiment 4 found that gap detection improved with
      increasing N but by a factor greater than the square root of N expected on
      statistical grounds. Examination of the underlying psychometric functions
      confirmed this effect. The results of these experiments suggest that, for energy
      increments, the auditory system integrates information from across the spectrum
      in a statistically independent manner, at least over the frequency range examined
      here. This does not appear to be the case for the detection of energy gaps or
      decrements.

PMID- 9265758
TI  - The effects of randomizing values of interaural disparities on binaural detection
      and on discrimination of interaural correlation.
AB  - The purpose of this study was to assess whether randomizing (roving) baseline
      interaural parameters of binaural stimuli would adversely affect performance in
      masking-level differences and in interaural correlation-discrimination paradigms.
      Listeners' detection thresholds were measured in NoSo and NoS pi configurations
      for both broadband (100-3000 Hz) and narrow-band (450-550 Hz) maskers centered at
      500 Hz. In addition, thresholds of interaural decorrelation (from a reference
      correlation of 1.0) were measured for 100-Hz-wide bands of noise centered at 500
      Hz. Data were obtained under conditions in which either values of ITD or values
      of IID were roved both within and across trials. Data were also collected in the
      absence of a rove. The range of the rove was +/- 500 microseconds for ITDs and
      was +/- 6 dB for IIDs. The duration of the stimuli was varied between 17 and 310
      ms. Overall, the results indicate that, independent of duration, roving the
      interaural cues produced small degradations of performance as compared to data
      obtained in the absence of a rove. The data are inconsistent with the notion that
      binaural detection depends upon reliable changes in laterality produced by adding
      S pi signals to diotic maskers. On the other hand, the data are consistent with
      modern models of binaural processing.

PMID- 9265759
TI  - Characteristics of a pulsating jet through a small modulated orifice, with
      application to voice production.
AB  - A detailed understanding of the aerodynamics of air flow in the larynx and the
      vocal tract is needed to refine physiological models of human voice production.
      This understanding can be applied in speech synthesis, voice diagnostics, and
      voice recognition. To date, most aeroacoustic models of phonation have been based
      on Bernoulli's orifice theory, i.e., the assumption that flow phenomena within
      the larynx are "quasi-steady." This assumption, however, has never been
      rigorously verified experimentally. In this study, detailed aerodynamic
      measurements were performed of a pulsating open jet through a modulated orifice
      with a time-varying area. Orifice geometry and characteristic Reynolds numbers
      and Strouhal numbers of the pulsating jet flow were representative of speech
      production. Simple source-filter models based on the quasi-steady flow assumption
      and an ideal one-dimensional monopole source model were found to yield
      satisfactory velocity, flow rate, and dynamic pressure predictions for most of
      the duty cycle. Significant deviations from quasi-steady behavior were observed
      only during the early part of the duty cycle, where the flow velocity in the
      center core rapidly reached a peak value immediately after release of the false
      folds. This acoustic near-field phenomenon did not affect the pressure waves
      generated by the pulsating jet through the orifice, propagated in the long rigid
      tube upstream of the orifice. The impact on this phenomenon on actual sound
      generation within the larynx, and wall pressures on the vocal folds, is not
      clear.

PMID- 9265760
TI  - Perceptual compensation for coarticulation by Japanese quail (Coturnix coturnix
      japonica).
AB  - When members of a series of synthesized stop consonants varying in third-formant
      (F3) characteristics and varying perceptually from /da/ to /ga/ are preceded by
      /al/, human listeners report hearing more /ga/ syllables than when the members of
      the series are preceded by /ar/. It has been suggested that this shift in
      identification is the result of specialized processes that compensate for
      acoustic consequences of coarticulation. To test the species-specificity of this
      perceptual phenomenon, data were collected from nonhuman animals in a syllable
      "labeling" task. Four Japanese quail (Coturnix coturnix japonica) were trained to
      peck a key differentially to identify clear /da/ and /ga/ exemplars. After
      training, ambiguous members of a /da/-/ga/ series were presented in the context
      of /al/ and /ar/ syllables. Pecking performance demonstrated a shift which
      coincided with data from humans. These results suggest that processes underlying
      "perceptual compensation for coarticulation" are species-general. In addition,
      the pattern of response behavior expressed is rather common across perceptual
      systems.

PMID- 9265761
TI  - Detection of temporal gaps in noise in dolphins: evoked-potential study.
AB  - Temporal resolution of hearing was studied in bottlenosed dolphins by recording
      the auditory brain-stem response (ABR) evoked by gap in noise. Gaps shorter than
      0.5 ms evoked a response combining both off- and on-components; longer gaps
      evoked separate off- and on-responses. Both the response to a short gap and on
      response to the end of a long gap increased with increasing gap duration. On
      response recovered completely at gap duration of 5-10 ms. Small but detectable
      response arose at gap duration as short as 0.1 ms. Contrary to the on-response
      after a long silence, the response to a short gap was less dependent on noise
      intensity. From these data, the temporal transfer function of the supposed
      integrator was derived assuming nonlinear transform of the integrator output to
      ABR amplitude. Equivalent rectangular duration of the found temporal transfer
      function was 0.27 ms.

PMID- 9265762
TI  - Simulation of ultrasonic pulse propagation through the abdominal wall.
AB  - Ultrasonic pulse propagation through the abdominal wall has been simulated using
      a model for two-dimensional propagation through anatomically realistic tissue
      cross sections. The time-domain equations for wave propagation in a medium of
      variable sound speed and density were discretized to obtain a set of coupled
      finite-difference equations. These difference equations were solved numerically
      using a two-step MacCormack scheme that is fourth-order accurate in space and
      second-order accurate in time. The inhomogeneous tissue of the abdominal wall was
      represented by two-dimensional matrices of sound speed and density values. These
      values were determined by processing scanned images of abdominal wall cross
      sections stained to identify connective tissue, muscle, and fat, each of which
      was assumed to have a constant sound speed and density. The computational
      configuration was chosen to simulate that of wavefront distortion measurements
      performed on the same specimens. Qualitative agreement was found between those
      measurements and the results of the present computations, indicating that the
      computational model correctly depicts the salient characteristics of ultrasonic
      wavefront distortion in vivo. However, quantitative agreement was limited by the
      two-dimensionality of the computation and the absence of detailed tissue
      microstructure. Calculations performed using an asymptotic straight-ray
      approximation showed good agreement with time-shift aberrations predicted by the
      full-wave method, but did not explain the amplitude fluctuations and waveform
      distortion found in the experiments and the full-wave calculations. Visualization
      of computed wave propagation within tissue cross sections suggests that amplitude
      fluctuations and waveform distortion observed in ultrasonic propagation through
      the abdominal wall are associated with scattering from internal inhomogeneities
      such as septa within the subcutaneous fat. These observations, as well as
      statistical analysis of computed and observed amplitude fluctuations, suggest
      that weak fluctuation models do not fully describe ultrasonic wavefront
      distortion caused by the abdominal wall.

PMID- 9265763
TI  - Bioacoustic behavior of African fishes (Mormyridae): potential cues for species
      and individual recognition in Pollimyrus.
AB  - An analysis of the natural bioacoustic signals made by two closely related
      African fishes (P. adspersus and P. isidori) revealed that these species
      separated along several acoustic dimensions that are likely to be important for
      species isolation. Both species produced grunts that were composed of a trains of
      pulses, but the pulse repetition rates were distinctly different (56 +/- 3 s.d.
      vs 44 +/- 4 s.d. pps). Complex tone bursts (moans) were also used, but the
      species differed substantially in the location of the fundamental peak (240 Hz +/
      12 s.d. vs 332 Hz +/- 34 s.d.). Some P. adspersus males sustained these tones
      for over a second (812 ms +/- 495 s.d.), whereas P. isidori produced shorter
      tones (121 ms +/- 35 s.d.). During interactions with females, the two species
      produced the grunts and moans in distinct species-typical patterns: P. adspersus
      males alternated grunts with moans and P. isidori produced a single grunt
      followed by a succession of moans. A detailed analysis of identified individual
      P. adspersus showed that acoustic features constituted individual signatures
      which could be used by conspecifics to identify individuals. Grunt spectral peak
      frequency was shown to be a good predictor of male mass, with peak frequency
      decreasing at 72 Hz per gram. Simulated standardized courtship encounters with
      females revealed that males differ markedly in their apparent ability to produce
      sustained moans and it is suggested that this may be particularly important to
      females in mate selection.

PMID- 9265764
TI  - Vocal tract length and formant frequency dispersion correlate with body size in
      rhesus macaques.
AB  - Body weight, length, and vocal tract length were measured for 23 rhesus macaques
      (Macaca mulatta) of various sizes using radiographs and computer graphic
      techniques. linear predictive coding analysis of tape-recorded threat
      vocalizations were used to determine vocal tract resonance frequencies
      ("formants") for the same animals. A new acoustic variable is proposed, "formant
      dispersion," which should theoretically depend upon vocal tract length. Formant
      dispersion is the averaged difference between successive formant frequencies, and
      was found to be closely tied to both vocal tract length and body size. Despite
      the common claim that voice fundamental frequency (F0) provides an acoustic
      indication of body size, repeated investigations have failed to support such a
      relationship in many vertebrate species including humans. Formant dispersion,
      unlike voice pitch, is proposed to be a reliable predictor of body size in
      macaques, and probably many other species.

PMID- 9265765
TI  - Characterization of serotype II polysaccharide antigen of group E streptococci
      using a monoclonal antibody.
AB  - A Monoclonal antibody (MAb II-T) specific for serotypes II and V Group E
      streptococci (GES) was prepared by fusing myeloma cells with spleen cells of mice
      immunized with whole cells of a serotype II strain. MAb II-T reacted in an enzyme
      immunoassay (EIA) with whole cells of both serotypes and reacted in gel diffusion
      test with autoclaved-saline extraction of serotypes II and V. The extract was
      purified by DEAE-Sephadex A-25, followed by treatment with proteinase K, and
      further by chromatography with a Sephadex G-200 column. The purified
      polysaccharide (PS) antigen contained 98.6% carbohydrate and 1.4% protein, but no
      detectable phosphorus. In hapten inhibition tests using various sugars, D
      mannosamine markedly inhibited the precipitin reaction. These results indicated
      that the antigenic determinant might have a structure similar to D-mannosamine.

PMID- 9265766
TI  - Shot-gun phage display mapping of two streptococcal cell-surface proteins.
AB  - We have used a phage display shot-gun cloning technique to map the binding
      domains in two cell surface proteins from animal group C streptococci. The
      proteins, MAG and ZAG, have affinity for alpha (2)-macroglobulin (alpha (2)M),
      serum albumin and IgG. In this work, parts of cloned i mag and zag genes were
      randomly cloned into a phagemid vector, and recombinant phages expressing alpha
      (2)-M- or albumin-binding activity were isolated through panning against
      immobilized alpha (2)M or albumin. Analysis of the clones revealed two distinct
      alpha (2)M-binding sites in protein MAG and two slightly overlapping binding
      sites in protein ZAG. The minimal albumin-binding domain in protein ZAG, as
      deduced from the affinity selected clones, consisted of 42 amino acids. These
      results show that the phage display shot-gun cloning is a rapid and convenient
      way to characterize the binding site(s) in receptor proteins without any prior
      knowledge of their number, size, and localization.

PMID- 9265767
TI  - A high level of accumulation of 2-hydroxymuconic 6-semialdehyde from aniline by
      the transpositional mutant Y-2 of Pseudomonas species AW-2.
AB  - Four transpositional mutants of aniline-assimilating Pseudomonas sp. AW-2
      produced 2-hydroxymuconic 6-semialdehyde (HMS) from aniline and accumulated it in
      a cultural medium. Among the four mutants, strain Y-2 produced the greatest
      amount of HMS (0.77 mg/ml) from 1 mg/ml of aniline hydrochloride in a 15-h
      growing culture. The conversion rate of aniline to HMS was 70% on a molar basis.
      Resting cells of strain Y-2 produced 0.65 mg/ml of HMS during 4h of incubation in
      a reaction mixture containing 1 mg/ml of aniline hydrochloride (conversion rate,
      60%). Transposon Tn5-Mob was found to be inserted into the gene of HMS
      dehydrogenase in strain Y-2 by sequence analysis.

PMID- 9265768
TI  - A microbiology investigation on probiotic pharmaceutical products used for human
      health.
AB  - Many and different probiotic pharmaceutical products are presently commercialised
      in the world. On this regard, a microbiological investigation was carried out to
      screen the microorganisms incorporated into these products, commonly used for
      human health. After determination of the cell number and viability of bacteria,
      several experiments were performed in vitro in order to characterise the
      microorganisms and to evaluate their probiotic value. Among all the strains
      identified, best results were obtained with Lactobacillus rhamnosus, Enterococcus
      faecium and Saccharomyces cerevisiae as far as regards growth rates, pH and bile
      salts tolerance. Moreover, the identification profiles of microorganisms showed a
      better reliability for the products containing a single species whereas the ones
      composed of different strains were usually not satisfactory. In some cases, the
      presence of Lactobacillus and Saccharomyces species was in disagreement with the
      claimed composition of the product and some species of lactobacilli,
      bifidobacteria and streptococci were found not viable. In defined mixed cultures
      experiments, the antagonism of Lactobacillus acidophilus and Enterococcus faecium
      versus Yersinia enterocolitica was demonstrated and explained as acid and/or
      antimicrobials production.

PMID- 9265769
TI  - Mycological and some physiological studies of keratinophilic and other moulds
      associated with sheep wool.
AB  - Wool samples of 50 healthy sheep collected from different localities at Ar' Ar in
      Saudi Arabia were examined for the presence of keratinophilic and other fungi
      using the hair plate technique. Forty-eight species and 2 varieties belonging to
      20 genera were isolated on Sabouraud's dextrose agar at 25 degrees C. Two species
      of true dermatophytes were isolated: Trichophyton terrestre and T. rubrum in low
      frequency of occurrence. Chrysosporium, a well-know keratinophilic genus, was the
      predominant genus on sheep wool. Of 6 Chrysosporium species isolated C. tropicum,
      C. keratinophilum and C. indicum were the most prevalent. Several other moulds
      could colonize wool, and the most frequent species were members of the genera
      Aspergillus, Penicillium, Emericella, Chaetomium and Acremonium. 14 isolates of
      selected fungi were screened for their ability to produce protease and keratinase
      on solid media. All test fungi exhibited protease, but with varying degree. It
      was observed that true dermatophytes Trichophyton rubrum, T. terrestre and the
      keratinolytic fungi Chrysosporium tropicum and C. keratinophilum showed highly
      keratinolytic activity, but Emericella nidulans var. lata, E. quadrilineata and
      Penicillium funiculosum were not able to attack horse hair.

PMID- 9265770
TI  - Production of cell wall polypeptides by different cell wall mutants of the
      unicellular green alga Chlamydomonas reinhardtii.
AB  - Three classes of cell wall-defective mutants of the unicellular green alga
      Chlamydomonas reinhardtii have been described in the literature differing with
      respect to the amounts of cell wall material and its attachment to the plasma
      membrane, respectively. We have compared the production of the chaotrope-soluble
      cell wall polypeptides by the different mutants. These experiments have been
      performed by comparative Western-blot analyses using antibodies raised (1)
      against the deglycosylation products of the insoluble wall fraction of wild-type
      cells, (2) against the deglycosylation product of the '150 kDa' chaotrope-soluble
      cell wall polypeptide and (3) against the carbohydrate side chains of the
      Chlamydomonas cell wall glycoproteins, respectively. Considerably different
      levels of cell wall polypeptides were found in the LiCl-extracts from intact
      cells of the various mutant strains containing the apoplastic, chaotrope-soluble
      cell wall glycoproteins. No correlation was found between the amounts and the
      patterns of cell wall glycoproteins present in the LiCl-extracts and the electron
      microscopical classification of the mutant strains. All the mutant strains were
      shown to contain the same amounts and patterns of intracellular cell wall
      precursors as wild-type cells as revealed by Western-blot analyses of urea-SDS
      lysates of LiCl-pretreated cells. These findings indicate that the different
      mutant strains produce the same set of cell wall polypeptides at the same
      relative amounts as wild-type cells. However, in the case of some strains
      belonging to different classes of cell wall mutants and showing differential
      seggregation patterns in crosses, alterations were observed for the pattern of
      extracellular cell wall polypeptides present in the LiCl-extracts from intact
      cells and in the culture medium, respectively.

PMID- 9265771
TI  - Production, purification and characterization of Bacillus lipase.
AB  - The lipolytic activities in the supernatant fractions of Bacillus cereus and
      Bacillus coagulans cultures were investigated. Aeration, agitation, different
      media, emulsified oils, inoculum size and phase of growth affected lipase
      production. Aeration was essential for lipase production (air: medium ration 4:1)
      and produced the highest activity. The lipolytic activity reached a maximum level
      after incubation for two days with continuous agitation. It was also elevated by
      the presence of either olive oil or tributyrin and with lesser extent in the
      presence of castor oil. The enzyme levels were drastically reduced in the
      presence of animal fat, cotton seed oil, margarine or glycerol. The extracellular
      lipase enzyme from Bacillus cereus was purified with 46.2% overall recovery
      thought too steps, an acetone precipitation of the whole supernatant and
      purification by gel filtration on sephadex G-100. The efficiency of the
      purification process was evaluated through the polyacrylamide gel
      electrophoresis. The enzyme has an optimum pH 7.5 at the optimum incubation
      temperature of 40 degrees C. It is stable and retains its full activity after
      heating at 40-50 degrees C for 30 min. The activity is lost completely at 80
      degrees C.

PMID- 9265772
TI  - Profiles of fragments after pulsed-field gel electrophoresis of cleaved genomic
      DNA from strains of Taylorella equigenitalis isolated from horses in Norway.
AB  - The genomic DNA of eight strains of Taylorella equigenitalis, isolated from seven
      Norwegian Trotters and a Norwegian pony with contagious equine metritis in
      Norway, was examined by pulsed-field gel electrophoresis after separate
      digestions with two restriction enzymes, namely, ApaI and NotI. The respective
      electrophoretic profiles of the fragments were essentially identical but differed
      from those of T. equigenitalis NCTC11184T and Kentucky 188. They also exhibited
      slight differences from profiles obtained from Japanese isolates. These results
      may possibly suggest a common genotype and a common source of infection for all
      these eight isolates in Norway.

PMID- 9265773
TI  - Growth kinetics, nutrient uptake, and expression of the Alcaligenes eutrophus
      poly(beta-hydroxybutyrate) synthesis pathway in transgenic maize cell suspension
      cultures.
AB  - Transgenic suspension cultures of Black Mexican Sweet maize (Zea mays L.)
      expressing the Alcaligenes eutrophus genes encoding enzymes of the pathway for
      biosynthesis of the biodegradable polymer poly(beta-hydroxybutyrate) (PHB) were
      established as a tool for investigating metabolic regulation of the PHB pathway
      in plant cells. Cultures were grown in a 2 L modified mammalian cell bioreactor
      and in shake flasks. Biomass doubling times for transgenic bioreactor cultures
      (3.42 +/- 0.76 days) were significantly higher than those for untransformed
      cultures (2.01 +/- 0.33 days). Transgenic expression of the bacterial enzymes
      beta-ketothiolase (0.140 units/mg protein) and acetoacetyl-CoA reductase (0.636
      units/mg protein) was detected by enzyme assays and immunoblots. However, over
      the first 2 years of cultivation, reductase activity decreased to 0.120 units/mg
      proteins. Furthermore, the PHB synthase gene, although initially present, was not
      detectable after 1.5 years of cultivation in suspension culture. These facts
      suggest that transgenic expression of PHB pathway genes in plant cells may not be
      stable. A hydroxybutyrate derivative was detected via gas chromatography even
      after 4 years of cultivation. Although the method used to prepare samples for gas
      chromatography cannot directly distinguish among PHB polymer, hydroxybutyryl-CoA
      (HB-CoA), and hydroxybutyric acid, solvent washing experiments indicated that
      most or all of the signal was non-polymeric, presumably H-CoA. The synthesis of
      HB-CoA appeared to be linked to substrate growth limitation, with HB-CoA
      accumulation increasing dramatically and cell growth ceasing upon depletion of
      ammonium. This suggests that the PHB synthesis pathway in plants is subject to
      regulatory mechanisms similar to those in prokaryotic cells.

PMID- 9265774
TI  - Inverse flux analysis for reduction of acetate excretion in Escherichia coli.
AB  - The determination of intracellular fluxes from the measurement of extracellular
      rates, a technique known as flux analysis, has been used successfully on several
      systems important to biotechnology. However, calculation of intracellular fluxes
      does not directly suggest ways to improve the performance of the cell. Here, we
      introduce a variation of this analysis, termed inverse flux analysis, which
      allows the prediction of the flux distribution as a function of manipulable
      internal fluxes. This approach is applied to analyze the acetate excretion
      problem commonly observed in aerobic Escherichia coli cultures. The effect of
      manipulating each flux is quantified by a flux distribution sensitivity
      coefficient, which is dependent on the stoichiometry. For the acetate excretion
      problem, our results suggest that the anaplerotic pathways, including the
      reactions catalyzed by phosphoenolpyruvate carboxylase and the glyoxylate bypass
      are the best choices for manipulating acetate excretion in E. coli. Increasing
      the anaplerotic flux will decrease acetate production while increasing the growth
      yield.

PMID- 9265775
TI  - Sequential delta-integration for the regulated insertion of cloned genes in
      Saccharomyces cerevisiae.
AB  - A novel delta-integration vector was developed to allow the sequential insertion
      of multiple cloned genes in the yeast Saccharomyces cerevisiae. To allow
      repetitive integrations, the reusable URA3 Blaster selection cassette was
      employed; the insertions (of CUP1p-lacZ in this study) were selected using the
      URA3 marker which was subsequently "popped" out by recombination between flanking
      direct repeats. Transformants contained only one new integrated copy after the
      loss of the URA3 marker, and subsequent transformations were effective for the
      sequential insertion of a series of genes (one at a time) into dispersed
      chromosomal delta sequences. The structural stability of the integrations was
      location-dependent (ranging from 75% to 100% after 50 generations in complex
      medium with or without gene expression), and the integrations (at least up to
      five) had no significant effects on the growth of the cells. In addition, beta
      galactosidase specific activity levels varied linearly with integrated copy
      number. The repetitive, regulated nature of integration with this vector is not
      possible with traditional delta-integration or other homologous recombination
      methods, and is promising for fine-tuning cloned gene copy number and for the
      insertion of metabolic pathway genes.

PMID- 9265776
TI  - Ubiquitin fusion technology: bioprocessing of peptides.
AB  - Ubiquitin fusion technology represents an emerging method for economically
      producing peptides and small proteins in the bacterium Escherichia coli. Our
      focus is on peptide production where the need for cost-effective, scaleable
      processes has recently been highlighted by Kelley (1996). There are two principal
      features: (1) the expression system consists of a suitable E. coli host strain
      paired with a plasmid that encodes the ubiquitin fusion and (2) an ubiquitin
      specific protease, UCH-L3, which cleaves only C-terminal extensions from
      ubiquitin. In this work, multigram yields were obtained of four ubiquitin fusions
      derived from cell paste generated in single 10-L fermentations. All were
      expressed intracellularly and remained soluble at extremely high levels of
      expression. Bacterial freeze--thaw lysates contained over 95% pure ubiquitin
      fusion protein. All four fusions were efficiently cleaved to ubiquitin and the
      peptide products. In one case, the final yield of peptide was 1.08 g from 3 L of
      low cell density bacterial culture. The combination of exceptional overexpression
      of the ubiquitin--peptide fusion proteins and a robust and specific protease are
      unique advantages contributing to a cost-effective, scaleable, and generic
      bioprocess for peptide production.

PMID- 9265777
TI  - Immobilization of potato tuber lipoxygenase on oxirane acrylic beads.
AB  - In this study, lipoxygenase from potato tuber has been purified by a method
      involving hydrophobic chromatography and the purified enzyme immobilized by
      covalent coupling to oxirane acrylic beads. The immobilized lipoxygenase
      exhibited increased long-term stability without a significant modification of the
      kinetic parameters. The comparative study on the effects of inhibitors such as
      dithizone, NDGA, phenidone, and beta-mercaptoethanol on the free and immobilized
      enzyme highlighted the importance of the lipoxygenase--support interaction,
      concluding that the immobilization process could cause the protection of the iron
      atom in the enzyme. The enzymatic specificity was maintained for the immobilized
      lipoxygenase, and their stability increased as compared to the free enzyme,
      making if feasible to use the enzyme in a multistep reaction to produce large
      quantities of leukotriene A4 or other related compounds of interest in the
      chemical industry and medicine.

PMID- 9265778
TI  - Intraparticle mass transfer in high-speed chromatography of proteins.
AB  - The effect of intraparticle mass-transfer resistances on the peak shape at high
      flow velocities in the range currently used in high-speed protein chromatography
      was investigated both theoretically and experimentally. The asymmetry of the
      protein bands under these conditions was quantified by the difference between the
      first moment and the retention volume of the peak apex, this being much easier to
      determine than the peak skewness. A general method is introduced for the
      evaluation of the mass-transfer characteristics of a given chromatographic
      sorbent from the variation in peak asymmetry with reduced velocity. The method is
      shown to be most useful when the number of theoretical plates is between 3 and
      300, which is the regime where peak asymmetry is prevalent. Measurements by
      isocratic elution under nonretained conditions were made on three chromatographic
      sorbents, each representing a general class of stationary phase configuration,
      i.e., gigaporous, mesoporous, and gel-filled gigaporous particles. Mass-transfer
      parameters were evaluated using the new method based upon the variation of the
      peak asymmetry with the fluid velocity. For the purpose of comparison, column
      mass transfer parameters were also evaluated from the variation in the reduced
      plate height with reduced velocity, a method most useful when the peak asymmetry
      is small and remains constant in the velocity range investigated. It is shown
      that the two methods are complementary and yield, within experimental error, the
      same intraparticle diffusion parameters. It was demonstrated using these methods
      that the diffusional behavior and the first moments of unretained eluites for the
      gel-filled gigaporous column packing correspond to a sorbent particle where
      eluites diffuse through liquid-filled pores containing a uniform distribution of
      solid cylinders, with the cylinders representing the polymer chains in the gel
      material. Similarly, the methods were used to verify that, at high flow rates,
      intraparticle convection can contribute substantially to the rate of
      intraparticle mass transfer in gigaporous column packings.

PMID- 9265779
TI  - Parameters affecting the efficiency of affinity-based reversed micellar
      extraction and separation (ARMES) in glycoprotein purification.
AB  - Affinity-based reversed micellar extraction and separation (ARMES) is an
      effective method for purifying both low and high molecular weight glycoproteins
      via liquid-liquid extraction. A range of extraction conditions were examined to
      gain insight into the mechanism of ARMES. Concanavalin A (Con A) was used as the
      model affinity ligand to bind soybean peroxidase (SBP) and beta-galactosidase as
      model glycoproteins. Factorial design was used to investigate the effect of
      various system variables on the extraction of SBP via ARMES. A quadratic model
      described the systems well, resulting in a standard deviation of 7% between
      calculated and experimental extraction efficiencies. Sensitivity analysis
      suggested that the key criteria in ARMES were the NaCl concentration and pH of
      the aqueous feed phase. Extraction of both glycoproteins decreased above pH 7 but
      fell to zero only at pH values significantly above the pI of the model
      glycoproteins and the Con A affinity ligand. It is proposed that the complex of
      the affinity lectin with the glycoprotein results in a sufficiently hydrophobic
      species that can be extracted into a reversed micellar organic phase even at pH's
      far above the pI's of the individual proteins that comprise the complex. This
      finding has practical considerations for the use of ARMES in the resolution and
      purification of protein glycoforms.

PMID- 9265780
TI  - Stoichiometry, kinetics, and regulation of glucose and amino acid metabolism of a
      recombinant BHK cell line in batch and continuous cultures.
AB  - Batch and continuous cultures were carried out to study the stoichiometry,
      kinetics, and regulation of glucose and amino acid metabolism of a recombinant
      BHK cell line, with particular attention to the metabolism at low levels of
      glucose and glutamine. The apparent yields of cells on glucose and glutamine,
      lactate on glucose, and ammonium on glutamine were all found to change
      significantly at low residual concentrations of glucose (< 5 mmol/L) and
      glutamine (< 1 mmol/L). The uptake rates of glucose and glutamine were markedly
      reduced at low concentrations, leading to a more effective utilization of these
      nutrients for energy metabolism and biosynthesis and reduced formation rates of
      lactate and ammonium. However, the consumption of other amino acids, especially
      the essential amino acids leucine, isoleucine, and valine and the nonessential
      amino acids serine and glutamate, was strongly enhanced at low glutamine
      concentration. Quantitatively, it was shown that the cellular yields and rates
      associated with glucose metabolism were primarily determined by the residual
      glucose concentration, while those associated with glutamine metabolism depended
      mainly on the residual glutamine. Both experimental results and analysis of the
      kinetic data with models showed that the glucose metabolism of BHK cells is not
      affected by glutamine except for a slight influence under glucose limitation and
      glutaminolysis not by glucose, at least not significantly under the experimental
      conditions. Compared to hybridoma and other cultured animal cells, the
      recombinant BHK cell line showed remarkable differences in terms of nutrient
      sensitivity, stoichiometry, and amino acid metabolism at low levels of nutrients.
      These cell-line-specific stoichiometry and nutrient needs should be considered
      when designing an optimal medium and/or feeding strategy for achieving high cell
      density and high productivity of BHK cells. In this work, a cell density of 1.1 x
      10(7) cells/mL was achieved in a conventional continuous culture by using a
      proper feed medium.

PMID- 9265781
TI  - Dual-fractal analysis for antigen--antibody binding kinetics for biosensor
      applications.
AB  - The diffusion-limited binding kinetics of antigen (or antibody) in solution to
      antibody (or antigen) immobilized on a biosensor and other surfaces is analyzed
      within a fractal framework. Often, the binding kinetics may be described by a
      single-fractal analysis. In some cases, the binding curve exhibits complexities.
      Then, for these cases, the dual-fractal analysis provides an improved fit when
      compared with a single-fractal analysis. This indicates a change in the reaction
      mechanism on the surface. It is of interest to note that the state of disorder
      (or the fractal dimension) and the binding rate coefficient both increase as the
      reaction progresses on the biosensor surface. For example, for the binding of 10
      nM insulin growth factor-1 in solution to insulin growth factor binding protein-1
      immobilized on a biosensor surface, a 64% increase in the fractal dimension from
      1.73 (Df1) to 2.85 (Df2) leads to an increase in the binding rate coefficient by
      a factor of 31.8 from 3.92 (k1) to 125 (k2). Furthermore, as the IGF-1
      concentration in solution increases from 10 to 80 nM in solution, k2 and Df2
      exhibit a linear increase. k1 and Df1 exhibit a linear increase with the
      reciprocal of the IGF-1 concentration in solution. The different examples
      analyzed and presented together provide a means by which the antigen-antibody
      reactions may be better controlled by noting the magnitude of the changes in the
      fractal dimension and in the binding rate coefficient as the reaction progresses
      on the biosensor surface. Also, the magnitude of the changes in the binding rate
      coefficients (k1 and k2) and in the fractal dimensions (Df1 and Df2) as different
      parameters are changed for the different biosensor applications are of particular
      value, since they provide us with a measure or extent of changes in the binding
      rate coefficient on changing different experimental parameter values. It is of
      interest to note the effect of different parameters on the extent or
      heterogeneity that exists on the surface and how this influences the binding rate
      coefficients. This may be one method to help manipulate or control the binding
      rate coefficients on the reaction surface.

PMID- 9265782
TI  - Monitoring embryo development in chicken eggs using acoustic resonance analysis.
AB  - Early embryonic development was monitored using acoustic resonance frequency
      analysis. Based on the course of the resonance frequency (RF) of a chicken egg
      during incubation, detection of viable and infertile eggs or eggs in which the
      embryo died during the first days of incubation was possible at the beginning of
      day 5. A sudden decrease of the RF of viable eggs was noticed after 96-104 h of
      incubation, whereas infertile eggs or eggs in which the embryo died during the
      first days of incubation showed a smooth, continuous increase of RF during the
      entire period of observation. Furthermore, the interruption of the embryonic
      development by cold storage after 24 or 84 h of incubation delayed the moment of
      decreasing RF. This proves that the sudden decrease of RF corresponds to a
      certain stage of development. This application of acoustic resonance frequency
      analysis offers the potential of early, automatic detection of inviable embryo's
      in eggs during incubation.

PMID- 9265783
TI  - Reverse micellar extraction of antibiotics from aqueous solutions.
AB  - Several antibiotics such as erythromycin, oxytetracyclin, benzylpenicillin, and
      actidione were extracted from aqueous buffers into reverse micellar solution of
      bis(2-ethylhexyl) sulfosuccinate sodium salt (AOT) in isooctane and recovered
      with high efficiency under mild conditions. Preliminary experiments with
      oxytetracycline dissolved in a fermentation broth indicate that the antibiotic
      can be selectively extracted from the broth and recovered efficiently without
      serious loss of potency.

PMID- 9265784
TI  - A species-specific recognition system directs haustorium development in the
      parasitic plant Triphysaria (Scrophulariaceae).
AB  - Parasitic plants use host molecules to trigger development programs essential for
      parasitism. One such program governs the initiation, development, and function of
      haustoria, parasite-specific organs responsible for attachment and invasion of
      host tissues. Haustoria development can be initiated by several different
      molecules produced by appropriate host species. We are interested in
      understanding how these signals are interpreted by two related facultative
      parasites, Triphysaria eriantha (Benth). Chuang and Heckard, and T. versicolor
      Fischer and C. Meyer, to distinguish their own roots from those of potential
      hosts. We used an in vitro bioassay to determine what proportion of different
      Triphysaria populations formed haustoria in the presence and absence of closely
      related and unrelated host species. We found that the proportion of plants with
      haustoria was the same whether the plants were grown in isolation or with a
      conspecific host. In contrast, a significantly higher proportion of plants made
      haustoria when the host was a congeneric Triphysaria. Plants with haustoria
      neither enhanced nor inhibited other plants' propensity to form haustoria.
      Together these results indicate that qualitative differences exist in haustorium
      inducing factors exuded by closely related species. The highest proportion of
      Triphysaria had haustoria when growth with Arabidopsis thaliana (L.) Heynh. Even
      in this case, however, some Triphysaria failed to develop haustoria.
      Interestingly, the percentage of haustoria that had vessel elements was higher
      when connections were made with Arabidopsis than with another Triphysaria. These
      results demonstrate that host recognition can be manifested at multiple points in
      haustorium development.

PMID- 9265785
TI  - Cell wall (1-->3)- and (1-->3, 1-->4)-beta-glucans during early grain development
      in rice (Oryza sativa L.).
AB  - Immunogold labeling was used to study the distribution of (1-->3)-beta-glucans
      and (1-->3, 1-->4)-beta-glucans in the rice grain during cellularization of the
      endosperm. At approximately 3-5 d after pollination the syncytial endosperm is
      converted into a cellular tissue by three developmentally distinct types of wall.
      The initial free-growing anticlinal walls, which compartmentalize the syncytium
      into open-ended alveoli, are formed in the absence of mitosis and phragmoplasts.
      This stage is followed by unidirectional (centripetal) growth of the anticlinal
      walls mediated by adventitious phragmoplasts that form between adjacent
      interphase nuclei. Finally, the periclinal walls that divide the alveoli are
      formed in association with centripetally expanding interzonal phragmoplasts
      following karyokinesis. The second and third types of wall are formed alternately
      until the endosperm is cellular throughout. All three types of wall that
      cellularize the endosperm contain (1-->3)-beta-glucans but not (1-->3, 1-->4)
      beta-glucans, whereas cell walls in the surrounding maternal tissues contain
      considerable amounts of (1-->3, 1-->4)-beta-glucans with (1-->3)-beta-glucans
      present only around plasmodesmata. The callosic endosperm walls remain thin and
      cell plate-like throughout the cellularization process, appearing to exhibit a
      prolonged juvenile state.

PMID- 9265786
TI  - The NADH-dependent Fe(3+)-chelate reductases of tomato roots.
AB  - The NADH-dependent Fe(3+)-chelate reductase (NFCHR) of tomato (Lycopersicon
      esculentum L.) roots, a strategy I species, was investigated. The Fe(3+)-citrate
      reductase (FeCitR) assay was strongly inhibited by p-hydroxymercuribenzoic acid
      (PHMB); moreover, the inhibitor was found to be more specific to the FeCitR assay
      than to the Fe(3+)-EDTA reductase assay, which was catalyzed by at least another
      reductase of 46 kDa. After high-speed centrifugation of tomato root membranes,
      high FeCitR activities were detected in pellets and lower activities in
      supernatants. After two-phase partitioning of microsomes, FeCitR activity (91
      nmol.min-1.mg-1) was less active in the upper phase (plasma membrane) than in the
      lower phase (277 nmol.min-1.mg-1). However, only the activity of the plasma
      membrane-associated NFCHR (FeCitR) was significantly enhanced (2.6-fold) in iron
      deficient tomato plants, whereas that of NFCHR in non-plasma-membrane rich
      fractions was unaffected by this treatment. The NFCHR obtained from
      lysophosphatidylcholine-solubilized plasma membrane was present as a 200-kDa
      protein complex following fast protein liquid chromatography on Superdex 200, or
      as a 28-kDa form following Blue Sepharose CL-6B chromatography. Both preparations
      were more active following iron starvation. Sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis showed that the 28-kDa protein purified from solubilized
      tomato microsomes or supernatant fractions by a final Mono Q step consisted of a
      single band of 32 kDa. Tomato root NFCHR resembled the NFCHR of maize (a strategy
      II plant, P Bagnaresi and P Pupillo, 1995, J Exp Bot 46: 1497-1503) in several
      properties: relative molecular mass, hydrophilicity, chromatographic behaviour,
      sensitivity to mercurials, specificity for electron donors and acceptors (e.g.
      cytochrome c), and a ferricyanide reductase-to-FeCitR ratio of 2.5. Preincubation
      with NADH partially protected NFCHR from PHMB-induced inactivation. Our data show
      that strategy I and II plants seem to share similar NFCHR proteins, which appear
      to belong to the cytochrome b5 reductase flavoprotein group.

PMID- 9265787
TI  - An abscisic-acid- and salt-stress-responsive rice cDNA from a novel plant gene
      family.
AB  - A novel cDNA clone osr40cl, encoding a abscisic acid (ABA)-responsive 40-kDa
      protein previously associated with salt tolerance (Moons et al. '1995' Plant
      Physiol 107: 177-186), was isolated from roots of rice seedlings (Oryza sativa
      L.). Exogenously applied ABA and salt shock induced a marked increase of the
      osr40cl transcript level in roots of seedlings whereas constant osr40cl mRNA
      levels were found in the shoot. The root-specific salinity-induced osr40cl mRNA
      accumulation was rapid and gradually declined upon prolonged salt shock. Plant
      growth regulators, signalling the wounding and the pathogen response, did not
      enhance osr40cl expression, indicating a salt- and osmotic-stress-specific
      response. The encoded OSR40cl protein was found to be hydrophilic, rich in
      histidine residues (6%) constituting putative metal-binding domains, and to
      consist of a duplicated domain of 151 amino acids (75% identical), that can form
      amphiphilic alpha-helical structures. The gene osr40cl belongs to a multigene
      family. Two osr40 genes were isolated, osr40g2 and osr40g3, tandemly arranged in
      an 8-kb region of the rice genome. Antisera raised against a conserved OSR40
      peptide recognized different OSR40 proteins that accumulated in roots upon
      exposure to salt stress. The OSR40 protein family included 29-KDa proteins and
      two 40-kDa proteins, the latter most probably corresponding to OSR40cl and
      OSR40g2 with duplicated domain structures. The osr40g3 transcript encoded a
      single copy of the OSR40 domain and exhibited a shoot-specific expression.
      Results indicate that OSR40cl plays a role in the adaptive response of roots to
      an hyper-osmotic environment and belongs to a novel plant protein family that
      most probably has structural functions.

PMID- 9265788
TI  - Expression of the ribosome-inactivating protein JIP60 from barely in transgenic
      tobacco leads to an abnormal phenotype and alterations on the level of
      translation.
AB  - In this paper we report the in-planta activity of the ribosome-inactivating
      protein JIP60, a 60-kDa jasmonate-induced protein from barley (Hordeum vulgare
      L.), in transgenic tobacco (Nicotiana tabacum L.) plants. All plants expressing
      the complete JIP60 cDNA under the control of the cauliflower mosaic virus (CaMV)
      35S promoter exhibited conspicuous and similar phenotypic alterations, such as
      slower growth, shorter internodes, lanceolate leaves, reduced root development,
      and premature senescence of leaves. Microscopic inspection of developing leaves
      showed a loss of residual meristems and higher degree of vacuolation of mesophyll
      cells as compared to the wild type. When probed with an antiserum which was
      immunoreactive against both the N- and the C-terminal half of JIP60, a
      polypeptide with a molecular mass of about 30 kDa, most probably a processed
      JIP60 product, could be detected. Phenotypic alterations could be correlated with
      the differences in the detectable amount of the JIP60 mRNA and processed JIP60
      protein. The protein biosynthesis of the transformants was characterized by an
      increased polysome/monosome ratio but a decreased in-vivo translation activity.
      These findings suggest that JIP60 perturbs the translation machinery in planta.
      An immunohistological analysis using the JIP60 antiserum indicated that the
      immunoreactive polypeptide(s) are located mainly in the nucleus of transgenic
      tobacco leaf cells and to a minor extent in the cytoplasm.

PMID- 9265789
TI  - Light-repressible receptor protein kinase: a novel photo-regulated gene from
      Arabidopsis thaliana.
AB  - To identify light-regulated genes in Arabidopsis thaliana (L.) Heynh. a clone was
      isolated which contains a cDNA fragment with sequence similarity to receptor-like
      protein kinases (RLKs). Sequence analysis of the corresponding genomic DNA as
      well as determination of transcribed regions revealed that the gene comprises 12
      exons. Sections of the deduced polypeptide exhibit homologies with kinase domains
      and the entire protein possesses structural features indicating that it is a
      novel member of the RLK family. The protein consists of a signal peptide, a
      putative receptor site including a leucine zipper region with a new motif, a
      transmembrane helix and 11 subdomains characteristic of serine/threonine kinases.
      The gene is designated light-repressible receptor protein kinase (lrrpk), as the
      specific mRNA is predominantly expressed in the absence of light. The lrrpk mRNA
      steady-state levels were assessed by competitive reverse transcriptase-polymerase
      chain reaction (RT-PCR) and found to be very low after light pulses, irrespective
      of the wavelength applied. Blue light was least effective in this respect, and
      the repression was not reversible by far-red light. Employment of in-situ RT-PCR
      revealed elevated lrrpk mRNA levels in the cotyledons of etiolated seedlings. The
      mRNA was also increased in the outer regions of the roots of greenhouse-grown A.
      thaliana, but was not detectable in any other part of the plants. An explanation
      of the relatively low lrrpk mRNA levels and the photophobic expression of the
      gene could be the finding that in the 5' upstream region of the lrrpk gene
      sequence elements are present that are similar to those identified in promoters
      of phytochrome A genes.

PMID- 9265790
TI  - Results and complications after posterior lumbar spondylodesis with the "Variable
      Screw Placement Spinal Fixation System".
AB  - Between March 1988 and March 1990, 45 patients underwent a spondylodesis using
      transpedicular screws and plates of the "Variable Screw Placement Spinal Fixation
      System". The indications for operation were spondylolisthesis (13),
      spondylolisthesis plus discopathy at the adjacent level (4), degenerative
      discopathy (13), pseudarthrosis after interbody fusion (7), disc herniations (4)
      and disc herniations plus degenerative discopathy of the adjacent segment (4). In
      1992, 43 patients were available for follow-up. The mean follow-up was 3.85
      years. Side effects or complications of a more permanent character were seen 25
      times in 43 patients. Eight patients had evidence of screw failure: loosening
      (5), fracture (2), and malposition (1). Complications, screw failure and
      reoperation all adversely affected clinical outcome. Overall only 60% of the
      patients reported a positive clinical outcome at follow-up. In our opinion
      transpedicular instrumentation is a logical system to provide rigid
      stabilisation, but it has a high learning curve. The original V.S.P. system with
      its bulky plates and screws appears to be particularly prone to giving a high
      rate of unwanted side effects not offset by a high clinical success rate.

PMID- 9265791
TI  - Cotrel-Dubousset instrumentation in idiopathic scoliosis a 5-year follow-up.
AB  - The results of Cotrel-Dubousset instrumentation in 50 patients with idiopathic
      scoliosis were evaluated. The patients were followed for 24 to 108 months with a
      mean follow-up of 5 years. Their average age was 15 years and 3 months. The
      scoliotic curves were classified according to King et al. There were 4 type I, 20
      type II, 10 type III, 10 type IV and 1 type V. Five curves could not be included
      in this classification: 2 double lumbar, 1 right lumbar and 2 left thoracic
      curves. Coronal plane analysis showed an average postoperative correction of 56%
      for thoracic curves and 57% for lumbar curves. The loss of correction at the most
      recent follow-up was 14% and 15%, respectively. Higher corrections were obtained
      in King types III and IV than in types I and II. Mild increase of thoracic
      kyphosis was noted in previously hypokyphotic curves. The normal sagittal curve
      in the lumbar spine was maintained at the most recent follow-up. There were no
      major neurological deficits. A symptomatic pseudarthrosis developed in one
      patient with a concomitant L5-S1 spondylolisthesis. Another patient developed a
      delayed deep wound infection that resolved after the instrumentation was removed.
      The data from this study suggest that Cotrel-Dubousset instrumentation achieves a
      satisfactory correction of the curves with an acceptable loss of correction over
      time. The system also preserves lumbar lordosis when fusion to the lower lumbar
      spine is required.

PMID- 9265792
TI  - The treatment of Lisfranc injuries.
AB  - Thirty-one patients with fracture-dislocations of the tarsometatarsal joint were
      examined to assess the functional end results after a mean follow-up of 2.9 years
      (range 20 to 56 months). Sixty-one percent were polytrauma patients; 39% suffered
      isolated fractures. Forty-five percent had associated lesions of the tarsal joint
      complex (Chopart and subtalar joint). According to the Baltimore Painful Foot
      Scoring System (PFS), 52% achieved an excellent or good result and 48% a fair or
      poor result. Of the four different treatment modalities, open reduction and
      temporary screw or K-wire fixation yielded the best results. The major
      determinants of acceptable results were the type of treatment, type of lesions,
      the quality of initial reduction and associated involvement of the tarsal joint
      complex. The extent of the initial injury was the determining factor in the
      development of late degenerative arthritis. Degenerative changes of the tarsal
      joint were seen in almost all cases (94%). Such changes were more frequent after
      temporary screw fixation but did not seem to influence the final results. An
      initial anatomical reduction did not guarantee excellent results but minimized
      the chance of late degenerative arthritis. Primary arthrodesis demonstrated no
      advantage in our series. Although partial arthrodesis may be necessary in
      severely comminuted joints, it cannot be routinely advocated and should be used
      as a salvage procedure.

PMID- 9265793
TI  - Psoas and adductor release in children with cerebral palsy.
AB  - In a retrospective study of 12 cerebral palsy patients with 17 hips treated for
      subluxation, clinical and radiographic results of psoas and adductor releases
      were reviewed. With an average follow-up of 4.05 years, the functional ability
      was improved in 3 spastic quadriplegics and 3 diplegics and maintained in 6 other
      patients. The CE-angle and femoral head coverage did not change significantly.
      The AC-index improved significantly (p = 0.01).

PMID- 9265794
TI  - Jumper's knee: results of surgical treatment.
AB  - The clinical results of 31 knees in 29 patients treated surgically for patellar
      tendinitis were reviewed. All patients suffered from stage 3 patellar tendinitis
      according to Roels et al., resistant to conservative treatment. A longitudinal
      strip of patellar tendon containing the pathologic tissue was resected in all
      cases without a bony procedure. Minimum follow-up time was 3 years (ranging from
      3 to 6 years). The results were very good in 26 knees, good in 1 knee and poor in
      4 knees. Persistent patellofemoral pain was considered the most important cause
      leading to a poor result. When patellofemoral pain due to maltracking is
      associated with patellar tendinitis, it seems logical that both pathologies
      should be addressed during surgical treatment.

PMID- 9265795
TI  - Is anatomical reduction of fractures of the fourth and fifth metacarpals useful?
AB  - Most fractures of the fourth and fifth metacarpals are treated conservatively.
      How necessary it is to pursue anatomical reduction of these fractures has not
      been determined. In order to evaluate whether anatomical reduction will result in
      a better outcome, two groups of one hundred patients each, were compared. One
      group had been treated with near-anatomical reduction. Only partial reduction had
      been accomplished in a control group with similar fractures. The residual
      radiographic angulation of the subcapital fracture at the four-week follow-up was
      measured in both groups, but no significant difference could be demonstrated. In
      shaft fractures, however, the anatomical reduction group showed significantly
      less residual angulation. Only reduction of shaft fractures is worthwhile in
      order to achieve a better anatomical outcome.

PMID- 9265796
TI  - Pronator quadratus muscle flap for the treatment of neuroma in continuity at the
      wrist.
AB  - The pronator quadratus can be prelevated as an island flap and used for coverage
      of neuromas at the wrist level. We have applied it with success in 4 patients.

PMID- 9265797
TI  - Clenched fist injury: a pitfall for patients and surgeons.
AB  - Clenched fist injuries or human bite-fight wounds are the result of an impact of
      the fist with the opponent's teeth, with perforation of the skin and joint.
      Severe septic arthritis of the third metacarpal joint of the dominant hand often
      occurs. The consequences, medical and legal, on the long run are important.

PMID- 9265798
TI  - Ochronotic arthropathy: the black hip. Case report and review of the literature.
AB  - Ochronosis is the dark pigmentation of connective tissues in patients with
      alkaptonuria. The latter is an autosomal recessive deficit of phenylalanine and
      tyrosine metabolism with various clinical manifestations. We report on a 63-year
      old man with familial ochronosis, who presented with a terminal degenerative
      right hip joint; his older brother had already been successfully treated at our
      department by total hip replacement. The postoperative course was uneventful and
      satisfactory for both.

PMID- 9265799
TI  - Wear of a titanium-alloy shoulder prosthetic head.
AB  - We present a case report of extensive wear that occurred on the surface of the
      titanium-alloy head of a shoulder prosthesis after only 2 years' service. Such
      wear warrants discontinuing the use of titanium-alloy articulating surfaces even
      in nonweight-bearing joints.

PMID- 9265800
TI  - An unusual localisation and presentation of an osteoid osteoma.
AB  - A case of osteoid osteoma of the scaphoid was discovered, in the absence of
      radiological (conventional and CT-scan) alterations. MRI findings were not
      conclusive.

PMID- 9265801
TI  - An unusual trigger finger.
AB  - A case of trigger finger due to a lipoma of the tendon sheath at the wrist is
      presented. Lipoma of the tendon sheath is a very rare tumor. In the case
      reported, the symptoms disappeared after surgical treatment.

PMID- 9265802
TI  - An unexpected complication of DVT prophylaxis.
AB  - We report a case in which a complication of routine chemoprophylaxis with
      subcutaneous low-molecular-weight heparin led to the postponement of a total hip
      replacement. This unusual reaction reinforces the current debate regarding the
      use of chemoprophylaxis for joint replacement surgery.

PMID- 9265803
TI  - Hypnotic involuntariness and the automaticity of everyday life.
AB  - We present a new theory of hypnotic involuntariness based on an integration and
      extension of recent social and cognitive theories on the automaticity of mundane,
      intentional behavior. According to this model, experiences of volition and
      involuntariness-in and out of hypnosis-are constructions or interpretations made
      possible by the high degree of automaticity that is a characteristic of all
      complex behavior, including novel behavior. Suggested nonvolitional behaviors are
      intentional acts that are triggered automatically by situational cues
      (suggestions) and cue-related sensations. The triggering of both the behaviors
      and the sensations are enabled by the formation of a generalized response
      expectancy, which is a cognitive set to respond appropriately to suggestions.
      Response expectancies are functionally equivalent to implementation intentions
      taking the form, "emit response x when situation y is encountered." The
      classification of a response set as either an expectancy or an intention and the
      experience of the response as volitional or nonvolitional depend on
      interpretations derived from instructional cues and prior beliefs.

PMID- 9265804
TI  - Goldfinger: a framework for resolving affect using ideomotor questioning.
AB  - The author presents a structured protocol for resolving repressed, suppressed or
      otherwise dated affect using ideomotor questioning. Essential to this model is a
      progressive ratification series which addresses affect, cognition and behavior. A
      questioning tree illustrates the method of affect inquiry and case examples
      demonstrate its application. This non-invasive, brief procedure is a useful
      adjunct to other treatment modalities and instrumental in clarifying the focus of
      treatment.

PMID- 9265805
TI  - Advantages and safeguards in using the ideomotor signaling technique: a
      commentary of Walsh and clinical practice.
AB  - Research and some of the valuable applications of ideomotor signaling are
      discussed. Then in a commentary on the uses and misuses of ideomotor signaling,
      and on Walsh's (1997) variant of this technique, safeguards are discussed,
      particularly concerning asking questions regarding the exploring of events from
      the past.

PMID- 9265807
TI  - Gurdjieff and ego-enhancement: a powerful alliance.
AB  - 24 housewives wishing to take more control over their lives were matched on their
      Control of Life Thermometer scores, one member of each pair being randomly
      allocated to either an Experimental or a Control group. While this latter group
      read material on how they might achieve the increased control they desired, the
      Experimental group had two 50-minute sessions during which they learned how to
      embed suggestions derived from the work of Gurdjieff into a framework designed to
      maximize their acceptance. The Control of Life Thermometer was administered on
      two further occasions, one immediately after completion of the second training
      session and one as a follow-up six months later. After completion of this first
      stage of the study, Control group housewives experienced the same two treatment
      sessions as had the Experimental group. Results indicated that control of life,
      as operationally defined by the Thermometer, was significantly greater both
      immediately after treatment and at the six month follow-up.

PMID- 9265808
TI  - Health beliefs of rural Appalachian women and the practice of breast self
      examination.
AB  - The purpose of this study was to examine the relationship between health beliefs
      of rural Appalachian women and the practice of breast self-examination (BSE). The
      sample consisted of 130 women residing in rural Appalachia who were recruited
      from various groups. The mean age was 53. They completed Champion's Health Belief
      Scale, which consisted of six Likert subscales: Susceptibility, Seriousness,
      Benefits, Barriers, Health Motivation, and Confidence. The women were questioned
      if they did BSE and were asked to respond to the following statement: "If I had
      cancer, I would rather not know it." Only 34.9% reported that they did monthly
      BSE. Two of the six subscales correlated significantly with reports of doing
      monthly BSE. Women who reported more confidence in doing BSE and perceived more
      benefits from doing BSE were significantly more likely to do regular exams.
      Interestingly, 18% indicated that they would rather not know if they had cancer
      and another 17% had neutral feelings. The findings support the need for
      culturally sensitive education programs on BSE for rural Appalachian women.
      Consideration must be given to their health beliefs in relation to health
      promotion.

PMID- 9265806
TI  - Hemodynamics following real and hypnosis-simulated phlebotomy.
AB  - Forearm arterial flow was measured in 22 healthy first-time blood donors during a
      300-ml. blood letting and during the subsequent recovery. Blood pressure (BP) was
      also taken simultaneously and forearm peripheral resistance calculated. Following
      a transient BP and flow increase due to tachycardia related to needle insertion,
      both systolic BP and flow progressively and significantly decreased, while
      resistance increased. In a further 22 sex- and aged-matched highly hypnotizable
      subjects, blood donation was simulated by means of verbal hypnotic suggestions.
      The BP, flow and resistance curves were similar to those obtained with the real
      blood letting, without any between-subject difference or group/time interaction.
      Mere hypnosis without suggestion of phlebotomy and the simple bed resting did not
      produce any effect. These results indicate that the hemodynamic changes observed
      during and after a blood loss are partly due to mental involvement rather than
      merely to the hydraulic effects of the removal of blood.

PMID- 9265809
TI  - Symptom distress in adult patients with cancer.
AB  - Symptom distress in the adult population with cancer is of concern to clinicians
      who care for these patients. Increased research has been directed toward the
      development and refinement of symptom distress scales, the identification of
      determinants of symptom distress, the investigation of symptom distress as a
      predictor, and the examination of the relationship between quality of life and
      symptom distress. Findings from this research have increased our understanding of
      symptom distress in adult patients with cancer. However, a major limitation of
      work to date has been a lack of consensus related to the definition and
      measurement of the symptom distress construct. The purpose of this article is to
      address existing conceptual and methodological challenges inherent in the study
      of symptom distress, and to make recommendations for further research in this
      area.

PMID- 9265810
TI  - Anxiety, needs, and coping in family members of the bone marrow transplant
      patient.
AB  - There is an imperative need in cancer nursing to recognize that family members of
      the patient undergoing bone marrow transplantation are unique in the outside
      stressors with which they must cope. These families have a multitude of needs to
      be addressed for them to be able to decrease their anxiety and be able to offer
      the emotional support the bone marrow transplant patient requires. The stressors,
      needs, and coping mechanisms of the cancer family, that may affect their outward
      behavior toward the patient and nursing staff, are outlined here. From this
      information, nursing interventions can be designed to help families decrease
      their anxiety and increase coping capabilities.

PMID- 9265811
TI  - Assessing sexual dimensions in Hispanic women. Development of an instrument.
AB  - The purpose of this study was to examine the psychometric properties of a
      culturally sensitive sexual functioning instrument, the Sexual Dimensions
      Instrument for Hispanic Women (SDIHW). Using a vignette, the respondent indicated
      her level of agreement with 26 items that were developed by Hispanic and Anglo
      nurses/researchers and validated by a panel of clinical and instrument experts.
      It was translated into Spanish and back-translated; the reading level was at the
      sixth to seventh grade. The convenience sample consisted of 179 Hispanic women
      being treated for gynecologic cancer as outpatients. The typical respondent was
      35-50 years of age, married, minimally acculturated, religious, and surviving for
      1-3 years; she had three or more children, had less than a high-school education,
      and had little sexual activity in the past month. A three-factor scale with 22
      items was determined to have conceptual clarity and moderate reliability (0.63
      0.77). Factors included role (eight items), personal sexual satisfaction (eight
      items), and relationship (six items). The instrument was completed in Spanish by
      60% of the respondents. Total and subscale scores were generally not influenced
      by demographic characteristics. The psychometric properties of the SDIHW indicate
      future research value. Moderate internal consistency, reliability, content, and
      construct validity were demonstrated. Achieving a better understanding of the
      Hispanic woman's perception of herself as a sexual being will aid the clinician
      in the development of culturally sensitive interventions.

PMID- 9265812
TI  - Similarities and differences in assessing nausea on a verbal category scale and a
      visual analogue scale.
AB  - The use of verbal category scales in assessing patient symptoms is evolving, but
      the extent to which reliability and precision are lost in using them as opposed
      to a visual analogue scale (VAS) remains uncertain. The present study analyzed
      the concordance between a four-point verbal category scale and a VAS in assessing
      nausea intensity in patients undergoing chemotherapy. The analysis of a total of
      348 simultaneous ratings by 104 women over four cycles revealed good concordance
      between the scales. The means of the VAS ratings (range 0-100 mm) corresponding
      to the four verbal categories divided the scale in four almost equally large
      parts (no nausea = 0.7, mild = 24.8, moderate = 48.3, severe = 75.1). However,
      the VAS ranges were wide. On an individual level a one-step change in the verbal
      category was associated with an average change of 20 mm on the VAS. The choice of
      scale to use should be based on the need in the particular situation. When
      measuring intensity of nausea in patients, the VAS is a reasonable choice due to
      its possibly greater ability to detect changes over time. On the group level,
      findings on a four-point category scale and a VAS on the average seem similar.

PMID- 9265813
TI  - A needs assessment for referral to occupational therapy. Nurses' judgment in
      acute cancer care.
AB  - As a step toward developing criteria for referral to occupational therapy, the
      study set out to assess patients' needs of occupational therapy in an acute
      cancer care hospital. A 31-item Needs Assessment Questionnaire was produced. It
      was intended to reflect interventions/ measures of occupational therapy.
      Seventeen questions eliciting information on occupational therapy gave a factor
      with an alpha coefficient of 0.92. Four single questions on occupational therapy
      did not form a factor. Six questions about the disease had an alpha coefficient
      of 0.83, whereas four about rehabilitation prognoses formed a factor with an
      alpha coefficient of 0.57. The questionnaire was completed by 40 day-shift
      primary-care nurses acting as key informants. Their answers concerned a total of
      88 of their patients. Twenty-six percent of the patients had been recommended for
      or referred to occupational therapy, whereas many whom the nurses judged to need
      this (47%) had not been referred (p = 0.01 chi-squared test, 10.59 McNemar test).
      Hence, no logical pattern of referral was found, and this seems to highlight both
      the absence of and the need for clear referral criteria.

PMID- 9265814
TI  - Consistency of patient information ... is this happening?
AB  - Most patients attending a hospital appointment are likely to feel at least
      slightly apprehensive and, therefore, unable to retain all of the information
      given to them. A patient visiting a department in which they had been diagnosed
      with cancer that required radiotherapy is perhaps one of the worst case
      scenarios. Both cancer and radiotherapy are words that create some of the
      greatest fears for the general public and, even, for members of the health
      profession. Due to the misconceptions about cancer and radiotherapy, patients
      require accurate information to help allay some of their fears. At the Department
      of Radiotherapy and Oncology, Freedom Fields Hospital, Plymouth, it was decided
      that an audit be used to determine the accuracy and consistency of information
      delivered within a specialized unit, before this information was disseminated to
      other departments within the hospital. The goals of the audit were to highlight
      possible weak areas of advice, to agree on the best information to furnish for a
      given situation, and to implement distribution of a staff handout to help achieve
      these aims. Staff members (n = 35) of various professions and levels were asked
      to complete a questionnaire relating to a patient with carcinoma of the breast
      undergoing a routine course of radiotherapy. Results of the audit indicated staff
      vagueness or conflicting responses in certain situations.

PMID- 9265815
TI  - Positron emission tomography: new hope for early detection of recurrent brain
      tumors.
AB  - Positron emission tomography (PET), the newest of the nuclear medicine imaging
      instruments, is now being used for diagnosis in 20 clinical sites in the United
      States. Recent approval of third-party reimbursement for PET scans for selected
      illnesses has set the precedence for wider clinical applications of this advanced
      diagnostic tool. Most practical of the newest applications of PET in the US is in
      early detection of recurrent brain tumors. Early detection not only saves lives,
      but also may save thousands of dollars in unnecessary tests, treatments, and
      surgeries. PET has two basic advantages over computerized tomography (CT) scans
      and magnetic resonance imaging (MRI). First, PET creates vastly superior images
      of metabolic activity, making possible more accurate and detailed diagnoses.
      Secondly, PET causes very low radiation absorption due to the volatile nature of
      the radioisotopes used. The rapidly increasing use of PET in clinical situations
      requires the nurse to become aware of its basic principles and applications, as
      well as the nursing care involved when a client is scheduled for a PET scan. This
      study serves to explain basic physical principles employed by PET. The historical
      development of PET and the comparison of PET with x-ray, CT, and MRI are
      reviewed. The article concludes with a discussion of future oncologic
      applications and the latest research developments in clinical use of PET scans.

PMID- 9265817
TI  - Public health: aseptic, not boring.

PMID- 9265818
TI  - Split shift.

PMID- 9265816
TI  - Genetic testing for cancer predisposition.

PMID- 9265819
TI  - Waging a noble war against a river.

PMID- 9265820
TI  - Floodwaters bring docs to the front.

PMID- 9265821
TI  - A partnership for public health.

PMID- 9265822
TI  - Public health response to the 1997 Minnesota flood. Lessons learned.

PMID- 9265823
TI  - Five years of work-related injuries and fatalities in Minnesota. Agriculture: a
      high-risk industry.
AB  - This report describes the Minnesota Fatality Assessment and Control Evaluation
      Study (MN FACE), a federally funded initiative to study fatal injuries in the
      workplace. The purpose of the program is to investigate various types of
      occupational fatalities and to identify risk factors that contribute to work
      related fatalities. Initially, the MN FACE program only investigated fatalities
      related to falls, confined spaces, and electrocutions. In 1994, MN FACE also
      began investigating fatalities associated with agricultural work. Agriculture
      continues to be one of the nation's most hazardous industries, ranking fourth
      among industries in the United States at high risk for work-related fatalities.
      MN FACE investigated 46 agriculture-related fatalities during 1994-95. Forty-one
      percent of the fatalities involved tractors, and 66% of these accidents were
      tractor rollovers. Other leading causes of agricultural fatalities included grain
      bin and manure pit asphyxiations.

PMID- 9265824
TI  - Minnesota takes on the tobacco industry.

PMID- 9265825
TI  - Supreme Court finds no 'right to die'.

PMID- 9265826
TI  - Tetanus: a case report.
AB  - Tetanus is a rare disease in the United States, with only 40 to 60 cases reported
      annually. This potentially lethal disease affects unimmunized or partially
      immunized persons, with the elderly at greatest risk. Tetanus usually follows an
      injury such as a puncture wound, abrasion, or laceration. The pathogen is an
      anaerobic, spore-forming, gram-negative, ubiquitous bacillus known as Clostridium
      tetani. In the vegetative form, it produces a lethal toxin, tetanospasmin, which
      enters the central nervous system through retrograde axonal transport, resulting
      in characteristic muscle spasms and tonic contractions. Severe tetanus can cause
      autonomic instability, respiratory arrest, and cardiac arrest. Patients with
      tetanus usually require intensive care with dose monitoring and extensive
      supportive care. Most patients experience full recovery with no signs of
      neurological sequelae. This case report and discussion illustrate the severity of
      the disease and the complexity of managing a patient with tetanus.

PMID- 9265827
TI  - Interview with Paul E. Wallner, DO. Interview by Bill Berlin.

PMID- 9265828
TI  - MSNJ's expert panel on late-term abortion. Medical Society of New Jersey.

PMID- 9265829
TI  - One breath at a time: treating asthma.

PMID- 9265830
TI  - Screening for colorectal cancer.

PMID- 9265831
TI  - Kids having kids: the teen birth rate.

PMID- 9265832
TI  - New Jersey's Clinical Laboratory Improvement Service.

PMID- 9265833
TI  - Patient privacy in the electronic age.

PMID- 9265834
TI  - PIP 21-day rule adds to physicians' burdens.

PMID- 9265835
TI  - Can we make New Jersey smoke-free?

PMID- 9265836
TI  - Esophageal candidiasis in HIV-negative patients.
AB  - Candida esophagitis is the most frequent esophageal infection in HIV seropositive
      as well as in seronegative patients. AIM: this retrospective study was designed
      to determine the characteristics of this disease in HIV negative patients in a
      general hospital. DESIGN: clinical records of all HIV negative patients with
      Candida esophagitis, which was endoscopically diagnosed and microscopically
      confirmed (biopsy and/or cytology of esophageal mucosa), were studied. RESULTS:
      thirty-one patients (23 men, 8 women, mean age: 65.4 +/- 14.3 years, median 71)
      fulfilled the criteria (0.56% of the diagnostic esophagogastroduodenal
      endoscopies). The most common clinical symptoms were dysphagia with or without
      odynophagia and pain (retrosternal, epigastric or xiphoid). Fourteen patients
      (45%) had no esophageal signs; in nine of them (29%) the disease was diagnosed in
      the course of an endoscopic exam to investigate the sources of acute or chronic
      anaemia. The most frequent predisposing factors were diabetes mellitus, oral or
      aerosolized corticotherapy, malignancies, treatment with broad-spectrum
      antibiotics and liver cirrhosis. Nine patients (29%) presented no known
      predisposing factors. The most common endoscopic appearance was grade II (51%).
      Sixty-one per cent of the patients exhibited at least one other
      esophagogastroduodenal endoscopic lesion associated with the mycosis. Three
      patients died of their underlying diseases within one week of the diagnosis of
      the candidiasis. Only one patient presented persistence of candidiasis one week
      after initiating treatment with oral nystatine. CONCLUSIONS: esophageal
      candidiasis is infrequent and does not always present with suspicious symptoms or
      known predisposing factors. Aerosolized corticotherapy may be a risk factor for
      the development of esophageal candidiasis.

PMID- 9265837
TI  - Epidemiological study of the prevalence of Helicobacter pylori infection in the
      general population in Asturias, Spain.
AB  - BACKGROUND: Helicobacter pylori is a worldwide infection, and it is estimated
      that approximately 50% of the general population is affected. However, its
      distribution varies considerably between developed and developing countries.
      AIMS: in the present study we report the results of an epidemiological
      investigation of the prevalence of H. pylori infection in the general population
      in Asturias (Northern Spain), in order to describe the current state of this
      infection in our region, and obtain figures for comparison with the results
      obtained in different communities of Spain and other countries. EXPERIMENTAL
      DESIGN: a descriptive transversal, epidemiological study, based on the
      serological determination of the IgG antibodies against H. pylori was carried out
      in the general population of a randomly selected sample of subjects without
      previous gastroduodenal antecedents. PARTICIPANTS: we analyzed 480 serum samples
      obtained from the general population of Asturias. These were divided into decades
      according to the age pyramid and tested for the presence of antibodies against H.
      pylori with a commercially available latex agglutination technique (Pyloriset).
      RESULTS: the global prevalence of H. pylori infection in our study was 226/480
      (49.2%), and was slightly higher in women (50.6%) compared to men (47.6%). No
      significant differences were found between sexes (p = 0.51). In the first decade
      mean prevalence was 13.6%. In the second this figure was 25.4%, and it increased
      steadily to a maximum in the sixth decade of 76.4%. Thereafter, the prevalence
      decreased to 66.6% in persons over 80 years of age. CONCLUSIONS: we found a high
      prevalence approximately 50% of H. pylori infection in the general population of
      Asturias, as in other epidemiological studies in Spain and other European
      countries. The distribution according to age shows a clear tendency to increase,
      from childhood to adolescence and adult life (50-60 years), when prevalence is
      highest (76%). From this decade onwards it begins to decrease, showing a clear
      cohort effect with a pattern intermediate between that of developed and
      developing countries.

PMID- 9265838
TI  - Response of chronic hepatitis C to interferon-alpha treatment and relationship
      with iron metabolism.
AB  - AIM: to prospectively analyze the influence of iron metabolism of the response to
      interferon-alpha therapy in chronic hepatitis C. METHODS: ninety-two patients
      with chronic hepatitis C treated with recombinant alpha-interferon were included.
      Basal serum levels of iron, ferritin and transferrin saturation were compared in
      responding and nonresponding patients. Additional epidemiologic, histologic and
      biochemical variables were studied as predictors of response to interferon-alpha
      therapy. RESULTS: we studied 57 men (62%) and 35 women (35%) with a mean age of
      40 years. Biopsy specimens were classified as having chronic active hepatitis
      (63%), chronic persistent hepatitis (33.8%) or cirrhosis (3.2%). The basal serum
      levels of iron and ferritin were significantly higher in non responders (126 +/-
      9.1 mu/dL and 222.7 +/- 31.9 eta g/dL respectively; p < 0.05) than in responders
      (101 +/- 5.7 micrograms/dL and 136 +/- 24.1 eta g/dL). Mean transferrin
      saturation was also higher in nonresponders (29.7% +/- 2.7% vs 26% +/- 2.02%)
      although this difference was not significant. Younger age, absence of cirrhosis
      and parenteral transmission were associated with an improved response to
      interferon therapy. No relationship was found between the presence of iron in the
      hepatic parenchyma and response to interferon treatment. CONCLUSIONS: elevated
      serum levels of iron, ferritin, or both may be associated with a worse response
      to interferon-alpha therapy.

PMID- 9265839
TI  - Treatment of chronic hepatitis C with interferon-alpha. Clinical histological and
      virological implications.
AB  - OBJECTIVE: to identify pretreatment predictive factors of long-term biochemical
      and virological response to interferon-alpha in chronic hepatitis C and to
      determine the effects of a second course of interferon-alpha in patients who
      responded but relapsed after interferon withdrawal. DESIGN: retrospective
      analysis. SETTING: outpatient liver clinic of a tertiary hospital in Spain.
      PATIENTS: 112 patients with chronic hepatitis C were treated with recombinant
      interferon-alpha (3 MU three times a week for 6 months). Twenty-four patients who
      responded but relapsed after interferon withdrawal were treated with a second
      course of interferon (3 MU three times a week for 12 months). RESULTS: seventy
      two patients were non-responders (64%), 11 patients had a sustained response
      (10%) and 29 patients responded but relapsed after interferon withdrawal (26%).
      Five (25%) of the 24 patients who relapsed and were treated with a second course
      of interferon experienced a sustained response (mean follow-up: 10 months). By
      multivariate analysis, four pretreatment variables were found to be predictive of
      a complete response: age < 40 years (p = 0.0004), history of IVDA (p = 0.001),
      low serum levels (p = 0.013), and genotype 3 (p = 0.01). Two variables were found
      to be predictive of a sustained response: short duration of HCV infection (p =
      0.09) and genotype 3 (p = 0.01). Sustained responders appeared to have lower HCV
      RNA levels than those with complete response who relapsed and non-responders. HCV
      viremia levels were not associated with the severity of liver histology, duration
      of disease or the source of hepatitis. CONCLUSIONS: in the present study a low
      sustained response rate was observed using a standard interferon-alpha regimen (3
      MU three times a week for 6 months). The sustained response rate increased
      slightly with a second course of interferon-alpha (3 MU three times a week for 12
      months) in patients with a complete response who relapsed after interferon
      withdrawal. Sustained response is related to viral genotype and duration of HCV
      infection.

PMID- 9265840
TI  - Ototoxicity of aminoglycoside drugs in tuberculosis treatment.
AB  - The possible ototoxic effect of kanamycin, streptomycin and a standard anti-TB
      drug combination, used in the treatment of 92 TB patients (7-71 years old), was
      examined by measuring the highest audible electric bone conduction frequency
      before and after treatment, using an Audimax 500 audiometer. At the so-called
      "safe" levels of drug administration it was found that kanamycin was markedly
      ototoxic, streptomycin very slightly ototoxic and the standard anti-TB drug
      combination had practically no ototoxic effect. Furthermore, it was found that
      none of these drugs were gender specific. Lastly, the possible effects of ageing
      on highest audible bone conduction frequency is discussed.

PMID- 9265841
TI  - The development of a screening schedule for use by teachers to describe the
      communication abilities of children with severe disabilities.
AB  - The study developed a screening schedule for teachers to describe the
      communication abilities of children with severe disabilities. Teachers were
      trained in the use of such an assessment procedure. Both the schedule as well as
      the training were evaluated. Results indicated that the schedule can be regarded
      as adequate for future use as teachers found it easy to use and applicable to
      their situation. Scoring the schedule requires more practise and training as this
      is a more advanced skill. Specific issues had an effect on the results, e.g., the
      teachers' familiarity with the type of disability observed, their qualifications
      and experience.

PMID- 9265842
TI  - Place pitch discrimination and speech recognition in cochlear implant users.
AB  - The considerable variability in speech perception performance among cochlear
      implant patients makes it difficult to compare the effectiveness of different
      speech processing strategies. One result is that optimal individualized processor
      parameter setting is not always achieved. This paper investigates the
      relationship between place pitch discrimination ability and speech perception to
      establish whether pitch ranking could be used as an aid in better patient
      specific fitting of processors. Three subjects participated in this study. Place
      pitch discrimination ability was measured and this information was used to design
      new channel to electrode allocations for each subject. Several allocations were
      evaluated with speech tests with consonant, vowel and sentence material. It is
      shown that there is correlation between the perceptual pitch distance between
      electrodes and speech perception performance. The results indicate that pitch
      ranking ability might be used both as an indicator of the speech perception
      potential of an implant user and in the choice of better electrode
      configurations.

PMID- 9265843
TI  - Nonspeaking children in schools for children with severe mental disabilities in
      the greater Pretoria area: implications for speech-language therapists.
AB  - The aim of this study was to describe children enrolled in registered schools for
      children with severe mental disabilities in the greater Pretoria area in order to
      compile a profile of nonspeaking children. Emphasis was placed on the prevalence
      of nonspeaking children as well as on their functioning in different skill areas
      in order to assess the need for service delivery. Two questionnaires were
      developed; the first for obtaining biographical data from teachers; the second
      for obtaining information on the communication and related abilities of children
      between 3-12 years. The particular teachers completed the questionnaires in
      conjunction with fieldworkers. Results indicated a high prevalence (38%) of
      nonspeaking children in schools for children with severe mental disabilities in
      the Pretoria area and also indicated that they were a heterogeneous group
      regarding communication and related abilities. This survey was the first step in
      determining prevalence and describing nonspeaking children in schools for
      children with severe mental disabilities in South Africa. Results also indicated
      that these children are in great need of additional service delivery with special
      reference to augmentative and alternative communication (AAC) strategy
      implementation.

PMID- 9265844
TI  - Communication intervention in an adolescent with profound cognitive impairment
      and autistic features.
AB  - The service delivery model currently used with a large proportion of profoundly
      cognitively impaired (PCI) persons, results in the under-utilization of their
      potential and often contributes to social isolation. By providing communication
      and independence training the self-actualisation potential and the right to power
      and control, is recognised. This single case study describes the implementation
      of a communication intervention model with a PCI adolescent. His mother was
      trained in the use of picture symbol task analysis as well as positive
      reinforcement to promote change in the adolescent's communication skills and
      independence. Results indicated significant changes in the skills of both
      participants and highlighted the mother's need for support to meet the demands of
      change.

PMID- 9265845
TI  - Early communication functioning of infants with cleft lip and palate.
AB  - This study investigated the early communication functioning and hearing abilities
      of 44 infants with cleft lip and palate, ages 3 to 31 months old. The results
      revealed that 64% of the subjects had a history of recurrent otitis media with
      effusion and 33% displayed associated anomalies. 26% of the subjects had mild
      hearing losses and middle ear pathology at the time of data collection. The
      subjects as a group displayed average developmental levels for perceptual
      cognitive, socio-personal and receptive language skills, but a limited phonetic
      repertoire and a statistically significant expressive language delay. The results
      indicated that the subjects experienced a motor developmental delay, but this was
      not statistically significant. The implications for early communication
      intervention are to conduct regular hearing measurements and to conduct regular
      parent-centered therapy with individualized home programmes. Efforts should be
      directed towards expanding early communication intervention services to include
      all infants with cleft lip and palate in South Africa.

PMID- 9265846
TI  - Speech-language evaluation of closed head injured subjects in South Africa:
      cultural applicability and ecological validity of a test battery.
AB  - This paper addresses the communicative outcome of a group of closed head injured
      (CHI) subjects in South Africa. Communicative outcome is evaluated on one test
      battery currently used for medico-legal assessments in South Africa. It was found
      that a number of the tests were sensitive to breakdown in this sample, but that
      the demographic factors of first language and pre-injury education significantly
      affected performance on some tests. Many test performances were significantly
      related to return to work, thus confirming the importance of communicative skills
      in the workplace, and the speech-language pathologist's role in vocational
      assessment and rehabilitation.

PMID- 9265847
TI  - Randomized controlled trials--the problem of clinical trials in veterinary
      science.

PMID- 9265848
TI  - How do anthelmintic drugs work?

PMID- 9265849
TI  - The costs of production diseases in dairy herds in England.

PMID- 9265851
TI  - Fallibility of plasma urea and creatinine as indices of renal function in
      diarrhoeic calves treated with conventional or nutritional oral rehydration
      solutions.
AB  - Changes in plasma urea, creatinine and glomerular filtration rate (GFR) were
      measured in calves before and after development of diarrhoea and during treatment
      with a conventional (WHO-type) or a nutritional oral rehydration solution (ORS).
      Changes in urea and creatinine failed to represent the extent of pre-renal
      failure. The two ORSs differed in their impact on GFR with the nutritional ORS
      improving GFR whereas with the WHO-type solution it deteriorated further.

PMID- 9265850
TI  - Modes of action of anthelmintic drugs.
AB  - Modes of action of anthelmintic drugs are described. Some anthelmintic drugs act
      rapidly and selectively on neuromuscular transmission of nematodes. Levamisole,
      pyrantel and morantel are agonists at nicotinic acetylcholine receptors of
      nematode muscle and cause spastic paralysis. Dichlorvos and haloxon are
      organophosphorus cholinesterase antagonists. Piperazine is a GABA (gamma-amino
      butyric acid) agonist at receptors on nematode muscles and causes flaccid
      paralysis. The avermectins increase the opening of glutamate-gated chloride
      (GluCl) channels and produce paralysis of pharyngeal pumping. Praziquantel has a
      selective effect on the tegument of trematodes and increases permeability of
      calcium. Other anthelmintics have a biochemical mode of action. The benzimidazole
      drugs bind selectively to beta-tubulin of nematodes, cestodes and fluke, and
      inhibit microtubule formation. The salicylanilides: rafoxanide, oxyclozanide,
      brotianide and closantel and the substituted phenol, nitroxynil, are proton
      ionophores. Clorsulon is a selective antagonist of fluke phosphoglycerate kinase
      and mutase. Diethylcarbamazine blocks host, and possibly parasite, enzymes
      involved in arachidonic acid metabolism, and enhances the innate, nonspecific
      immune system.

PMID- 9265852
TI  - The costs of production diseases in dairy herds in England.
AB  - Economic losses due to common health problems in dairy cattle were investigated
      in 90 Friesian/Holstein herds (average size 152 cows), which calved in England
      during the 1992/1993 season with an average annual yield of about 6000 l per cow.
      By using only the direct costs of common production diseases and other health
      problems (mastitis, lameness, vulval discharge, treatments for oestrus-not
      observed, retained foetal membranes, milk fever, twinning, calf mortality and aid
      at calving), the cost of ill health in a 100 cow herd with average rates of these
      problems (compared with target levels) was estimated at Pounds 6300 per year. The
      costs ranged from Pounds 1200 (average of the top 10%) to Pounds 13600 (average
      of the worst 10% of the herds). The main losses were due to mastitis and lameness
      (38 and 27% of health cost, respectively).

PMID- 9265853
TI  - Equine dyschondroplasia (osteochondrosis)--histological findings and type VI
      collagen localization.
AB  - This study describes (1) the histological appearance of dyschondroplasia, the
      primary lesion of osteochondrosis, in articular cartilage of the horse and (2)
      the localization of type VI collagen which is an important constituent of the
      extracellular matrix (ECM). Dyschondroplastic cartilage was identified on the
      basis of the presence of cartilage cores (i.e., cartilage extending into the
      subchondral bone) and confirmed with subsequent histological examination. Full
      thickness cartilage samples from 57 horses were collected and paraffin embedded.
      Histological examination was used to examine the normal architecture of equine
      growth cartilage and to determine the presence of various pathological changes in
      dyschondroplastic lesions. Immunolocalization was used to identify type VI
      collagen in normal and dyschondroplastic lesions. The abnormalities observed in
      the dyschondroplastic cartilage fell into two groups. In Group A (n = 18) the
      lesions were associated with a disruption in the normal sequential transition of
      the chondrocytes through proliferation and maturation resulting in an
      accumulation of large numbers of small, rounded chondrocytes. A decrease in type
      VI collagen immunoreactivity compared with normal animals was detected except
      around chondrocyte clusters. Group B lesions (n = 9) were characterized by an
      alteration in the staining pattern of the mineralized cartilage and underlying
      bone. In these lesions type VI collagen immunoreactivity was increased. In both
      groups the presence of retained blood vessels, chondrocyte clusters,
      chondronecrosis and fissure formation was detected. These two histologically
      distinct groups suggest that equine dyschondroplasia may be comprised of
      different pathological entities and that it is associated with alterations in the
      pattern of distribution of an ECM protein.

PMID- 9265854
TI  - Evaluation of extradural xylazine injection for caesarean operation in ovine
      dystocia cases.
AB  - Twenty-eight sheep suffering from dystocia, with complications including vaginal
      prolapse and emphysematous foetuses, were treated by caesarean operation. When
      tested by needle prick 30-40 min after injection, analgesia of the flank was
      present in 12 of 13 ewes and eight of nine ewes following either sacrococcygeal
      or lumbosacral extradural xylazine, respectively at a dose rate of 0.07 mg kg-1.
      Twelve of 13 ewes, which were ambulatory at the time of extradural injection,
      exhibited pelvic paresis in the interval before surgery. Vaginal prolapses
      associated with the dystocia in seven of 22 ewes which were replaced during
      surgery but not retained by suture, did not recur.

PMID- 9265855
TI  - Viral proteins of bovine papillomavirus type 4 during the development of
      alimentary canal tumours.
AB  - In cattle infection of the upper alimentary canal mucosa by bovine papillomavirus
      type 4 (BPV-4) results in the development of papillomas which can progress to
      cancer in animals fed on bracken fern. This paper describes a study of the
      cellular and subcellular distribution of a number of different BPV-4 products in
      experimentally-induced BPV-4 tumours. E8 and E4 proteins were detected solely as
      cytoplasmic antigens in the undifferentiated and differentiated layers of the
      papilloma, respectively; L2 was detected solely as a nuclear antigen in the
      differentiated layers, whereas E7 was present in either the nucleus or the
      cytoplasm depending on the differentiation stage of the keratinocyte. Replicative
      forms of viral DNA were detected from the spinous to the squamous layers. Viral
      antigens were not detected during papilloma regression or in carcinomas. E8 was
      most prominent in early developmental stages, while E4 and L2 were most abundant
      in mature papillomas. E7 was present in large amounts in both early and mature
      stages, declining at later stages. These results suggest a temporal and spatial
      requirement for the expression and function of the viral proteins.

PMID- 9265856
TI  - Studies on the age of puberty of male camels (Camelus dromedaries) in Saudi
      Arabia.
AB  - Aspects of sexual development and attainment of sexual and breeding maturity were
      studied in two groups of Najdi camels (Mojaheem and Wadah), maintained in stalls
      under good nutritional conditions. Body weight, testes diameter and degree of
      penile freedom were recorded weekly. Sexual maturity was assessed by the
      examination of semen collected by an artificial vagina. Puberty was defined as
      the stage when the animal was able to produce viable sperms. Mating, followed by
      strong jerks and ejaculation of mature sperms, was taken to indicate onset of
      breeding maturity. Mojaheem camels reached sexual maturity at a significantly
      younger age and heavier weight (164 weeks and 360 kg) than Wadah camels (182
      weeks and 336.5 kg) (P < 0.001). Complete separation of the penis from preputial
      adhesions occurred at an average age of 138.6 weeks in both breeds. At the point
      of sexual maturity, the mean percentage of live spermatozoa was 65.1 +/- 5.2
      while percentage of abnormal sperms was 17.6 +/- 2.2; total motility was 40 +/-
      16% and progressive motility (48 +/- 2.2% (semen pH range 7.8-8.2). The
      percentage of live sperm was 65 +/- 1.5 (normal sperms 82 +/- 4). It is suggested
      that the encouragement of rapid growth during the pubertal period in camels
      managed under good nutritional and environmental conditions could assist early
      sexual development and breeding maturity.

PMID- 9265858
TI  - Current and future NIH support of biomedical research.
AB  - Current and future prospects for biomedical research are discussed by examining
      two critical questions, namely, how much money will be available and how it will
      be spent. Context is provided first by comparing how those same questions were
      answered 25 years ago with what has actually occurred between 1972 and the
      present. The questions are then addressed for a comparable period in the future.
      Projections are made for future funding for the National Institutes of Health
      (NIH) and examples of new research directions are described. Ample grounds are
      provided for optimism about the future of biomedical research and NIH funding for
      it.

PMID- 9265857
TI  - Delayed bottle weaning and iron deficiency in southeast Asian toddlers.
AB  - We undertook this study to determine if culturally influenced feeding practices
      are associated with iron deficiency in infants and toddlers from low-income
      families. We obtained a dietary survey, illness history, hematocrit, and zinc
      protoporphyrin-to-heme ratio (ZPP/H) from 35 Southeast Asian children and 73
      children of other ethnicities between ages 5 and 30 months. We confirmed iron
      deficiency by serum ferritin measurement in children with ZPP/H > 80 mmol/mol or
      evaluated them after a 3-month iron treatment. Sixty percent of the Southeast
      Asian children had elevated ZPP/H ratios, compared with 14% of children of other
      ethnicities. Follow-up studies confirmed iron deficiency in 12 of 21 Southeast
      Asian children with elevated ZPP/H; 75% (eight) of those with confirmed iron
      deficiency were 24 to 30 months of age. We found that toddler feeding practices
      differ between Southeast Asians and other ethnic groups. All 17 Southeast Asian
      toddlers were still bottle fed at their second birthday, compared with 10 of 21
      same-age children of other ethnicities. Persistence of bottle feeding after 2
      years of age was highly associated with elevation of ZPP/H in Southeast Asian
      children but not in other children. Clinicians need to be aware of this problem
      and carefully monitor iron status in children not weaned from the baby bottle by
      age 2 years. Changes in education practices and policies are needed to prevent
      iron deficiency from the overintake of cow's milk that results from prolonged
      bottle feedings in this ethnic group.

PMID- 9265859
TI  - Motor vehicle crashes and maternal mortality in New Mexico: the significance of
      seat belt use.
AB  - In recent years, as deaths from medical complications during pregnancy have
      declined, injuries-specifically those sustained in motor vehicle crashes
      represent a growing proportion of all pregnancy-associated deaths. To investigate
      pregnancy-associated deaths in motor vehicle crashes in New Mexico, we
      scrutinized the database of the New Mexico Office of the Medical Investigator for
      all deaths during pregnancy and up to 6 weeks postpartum from 1986 through 1995.
      A total of 97 deaths were identified, 47 of which were injury-related. Motor
      vehicle crashes accounted for 33 (approximately 70%) of the injury-related
      deaths. We analyzed the data on motor vehicle crashes for decedent's age and
      ethnicity, fetal gestational age, time of crash, rural vs urban location of
      crash, seat belt use, and drug and alcohol use. Compared with non-Hispanic white
      women, proportionately higher numbers of Hispanic and American Indian pregnant
      women were killed in motor vehicle crashes. In searching for modifiable risk
      factors, we noted that 45% of the crashes involved alcohol and that the majority
      of pregnant women killed (77%) were not wearing seat belts at the time of the
      crash. We conclude that education about seat belt use during pregnancy (as well
      as the dangers of alcohol use and riding with intoxicated drivers while pregnant)
      is a promising strategy to reduce motor vehicle fatalities.

PMID- 9265861
TI  - Determining the number of copies of HIV-1 RNA in plasma: applying this new test
      to management of patients.

PMID- 9265860
TI  - Hepatitis G virus: is it a hepatitis virus?
AB  - Hepatitis G virus (HGV) and GB virus C (GBV-C) are two newly discovered viral
      agents, different isolates of a positive-sense RNA virus that represents a new
      genus of Flaviviridae. The purpose of this review is to analyze new data that
      have recently been published on the epidemiology and associations between HGV and
      liver diseases such as posttransfusion hepatitis, acute and chronic non-A-E
      hepatitis, fulminant hepatitis, cryptogenic cirrhosis, and hepatocellular
      carcinoma. The role of HGV in coinfection with other hepatitis viruses, the
      response to antiviral therapy, and the impact of HGV on liver transplantation are
      also discussed. HGV is a transmissible blood-borne viral agent that frequently
      occurs as a coinfection with other hepatitis viruses due to common modes of
      transmission. The prevalence of HGV ranges from 0.9 to 10% among blood donors
      throughout the world and is found in 1.7% of volunteer blood donors in the United
      States. The majority of patients infected with HGV by blood transfusion do not
      develop chronic hepatitis, but hepatitis G viremia frequently persists without
      biochemical evidence of hepatitis. Serum HGV RNA has been found in 0 to 50% of
      patients with fulminant hepatitis of unknown etiology and 14 to 36% of patients
      with cryptogenic cirrhosis. The association between HGV and chronic non-A-E
      hepatitis remains unclear. Although HGV appears to be a hepatotrophic virus, its
      role in independently causing acute and chronic liver diseases remains uncertain.

PMID- 9265862
TI  - Laboratory detection of Chlamydia trachomatis.

PMID- 9265863
TI  - Diseases associated with the major histocompatibility complex.

PMID- 9265864
TI  - Kaposi's sarcoma-associated herpesvirus (KSHV): a new viral pathogen associated
      with Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's
      disease.

PMID- 9265865
TI  - Cocaethylene: a novel cocaine homolog.

PMID- 9265866
TI  - AIDS-related lymphomas with neurologic manifestations.

PMID- 9265867
TI  - Wegener granulomatosis causing sellar mass, hydrocephalus, and global pituitary
      failure.

PMID- 9265868
TI  - An anterior mediastinal mass with draining sternal sinus tracts due to Nocardia
      braziliensis.

PMID- 9265869
TI  - The alphabet soup of viral hepatitis: is G a new flavi(or) in the mix?

PMID- 9265870
TI  - Onychomycosis--a different perspective.

PMID- 9265871
TI  - The role of actions in making inferences about the shape and material of solid
      objects among Japanese 2 year-old children.
AB  - This study examined whether 2 year-old children attend to the relevant properties
      (shape or material) of solid objects in making inferences when adults demonstrate
      appropriate actions. In Experiment 1, the experimenter presented 24 Japanese 2
      year-olds a nonsense label with an unfamiliar target solid object that was either
      rigid (e.g., steel) or flexible (e.g., sponge). The experimenter performed an
      action on the object that emphasized the shape (e.g., rolling) or the material
      (e.g., squeezing) of these targets. The experimenter then asked these children,
      given the same label, to chose an object that matched the target in shape or in
      material. In Experiment 2, the experimenter asked thirty-two Japanese 2 year-olds
      to choose an object with and without nonsense labels. The results showed that the
      children used action information to make their choices regardless of the presence
      of labels. As hypothesized, an adults's action information alone can direct
      children to attend to relevant object properties in making inferences about solid
      objects.

PMID- 9265872
TI  - Facial expression megamix: tests of dimensional and category accounts of emotion
      recognition.
AB  - We report four experiments investigating the perception of photographic quality
      continua of interpolated ('morphed') facial expressions derived from prototypes
      of the 6 emotions in the Ekman and Friesen (1976) series (happiness, surprise,
      fear, sadness, disgust and anger). In Experiment 1, morphed images made from all
      possible pairwise combinations of expressions were presented in random order;
      subjects identified these as belonging to distinct expression categories
      corresponding to the prototypes at each end of the relevant continuum. This
      result was replicated in Experiment 2, which also included morphs made from a
      prototype with a neutral expression, and allowed 'neutral' as a response
      category. These findings are inconsistent with the view that facial expressions
      are recognised by locating them along two underlying dimensions, since such a
      view predicts that at least some transitions between categories should involve
      neutral regions or identification as a different emotion. Instead, they suggest
      that facial expressions of basic emotions are recognised by their fit to discrete
      categories. Experiment 3 used continua involving 6 emotions to demonstrate best
      discrimination of pairs of stimuli falling across category boundaries; this
      provides further evidence of categorical perception of facial expressions of
      emotion. However, in both Experiment 1 and Experiment 2, reaction time data
      showed that increasing distance from the prototype had a definite cost on ability
      to identify emotion in the resulting morphed face. Moreover, Experiment 4 showed
      that subjects had some insight into which emotions were blended to create
      specific morphed images. Hence, categorical perception effects were found even
      though subjects were sensitive to physical properties of these morphed facial
      expressions. We suggest that rapid classification of prototypes and better across
      boundary discriminability reflect the underlying organisation of human
      categorisation abilities.

PMID- 9265873
TI  - The impact of orthographic consistency on dyslexia: a German-English comparison.
AB  - We examined reading and phonological processing abilities in English and German
      dyslexic children, each compared with two control groups matched for reading
      level (8 years) and age (10-12 years). We hypothesised that the same underlying
      phonological processing deficit would exist in both language groups, but that
      there would be differences in the severity of written language impairments, due
      to differences in orthographic consistency. We also hypothesized that systematic
      differences due to orthographic consistency should be found equally for normal
      and dyslexic readers. All cross-language comparisons were based on a set of
      stimuli matched for meaning, pronunciation and spelling. The results supported
      both hypotheses: On a task challenging phonological processing skills
      (spoonerisms) both English and German dyslexics were significantly impaired
      compared to their age and reading age controls. However, there were extremely
      large differences in reading performance when English and German dyslexic
      children were compared. The evidence for systematic differences in reading
      performance due to differences in orthographic consistency was similar for normal
      and for dyslexic children, with English showing marked adverse effect on
      acquisition of reading skills.

PMID- 9265874
TI  - About the influence of the presentation format on arithmetical-fact retrieval
      processes.
AB  - This article presents the results of two experiments. In Experiment 1, French
      speaking participants were asked first to retrieve the product of two numbers
      presented in Arabic or verbal code, and then to perform a number-matching task on
      the same material to assess the encoding time difference between numerals in the
      two formats. Experiment 2 involved the same multiplication task with Dutch
      speaking participants who name two-digit numbers in reverse order. The format
      effects obtained by Campbell and Clark (1992); Campbell (1994) for multiplication
      were replicated. However, several observations suggest that some of these effects
      may be due to encoding time differences between word and digit numerals. The same
      size-by-format interaction was found for the number-matching task as for the
      multiplication task, and the effect disappeared with practice in the
      multiplication task. Finally, despite the fact that the linguistic structure of
      number names differs between French and Dutch, the types of error produced in
      both groups were identical. The last result does not match with the hypothesis
      that operand intrusion errors are due to interference between reading processes
      and arithmetical-fact retrieval processes. Implications of these findings for the
      debate about the nature of arithmetical-fact retrieval are discussed.

PMID- 9265875
TI  - Research on discipline. The state of the art, deficits, and implications.

PMID- 9265876
TI  - Spanking by parents and subsequent antisocial behavior of children.
AB  - OBJECTIVE: To deal with the causal relationship between corporal punishment and
      antisocial behavior (ASB) by considering the level of ASB of the child at the
      start of the study. METHODS: Data from interviews with a national sample of 807
      mothers of children aged 6 to 9 years in the National Longitudinal Survey of
      Youth-Child Supplement. Analysis of variance was used to test the hypothesis that
      when parents use corporal punishment to correct ASB, it increases subsequent ASB.
      The analysis controlled for the level of ASB at the start of the study, family
      socio-economic status, sex of the child, and the extent to which the home
      provided emotional support and cognitive stimulation. RESULTS: Forty-four percent
      of the mothers reported spanking their children during the week prior to the
      study and they spanked them an average of 2.1 times that week. The more spanking
      at the start of the period, the higher the level of ASB 2 years later. The change
      is unlikely to be owing to the child's tendency toward ASB or to confounding with
      demographic characteristics or with parental deficiency in other key aspects of
      socialization because those variables were statistically controlled. CONCLUSIONS:
      When parents use corporal punishment to reduce ASB, the long-term effect tends to
      be the opposite. The findings suggest that if parents replace corporal punishment
      by nonviolent modes of discipline, it could reduce the risk of ASB among children
      and reduce the level of violence in American society.

PMID- 9265877
TI  - Toward a developmental-contextual model of the effects of parental spanking on
      children's aggression.
AB  - OBJECTIVE: To challenge the application of an unqualified social learning model
      to the study of spanking, positing instead a developmental-contextual model in
      which the effects of spanking depend on the meaning children ascribe to spanking.
      DESIGN: Population-based survey data from 1112 children aged 4 to 11 years in the
      National Survey of Families and Households. Controlled for several family and
      child factors including children's baseline aggression. MAIN OUTCOME MEASURES:
      Schoolyard fights and antisocial scores on the Behavior Problems Index at the 5
      year follow-up. RESULTS: Structural equation modeling yielded main effects (P <
      or = .05, change in chi 2) of children's age and race; spanking predicted fewer
      fights for children aged 4 to 7 years and for children who are black and more
      fights for children aged 8 to 11 years and for children who are white. Regression
      analyses within subgroups yielded no evidence that spanking fostered aggression
      in children younger than 6 years and supported claims of increased aggression for
      only 1 subgroup: 8- to 11-year-old white boys in single-mother families (P < or =
      .05, F test). CONCLUSIONS: For most children, claims that spanking teaches
      aggression seem unfounded. Other preventive effects and harmful effects of
      spanking may occur depending on the child and the family context. Further efforts
      to identify moderators of the effects of spanking on children's adjustment are
      necessary.

PMID- 9265878
TI  - Correlates and consequences of harsh discipline for young children.
AB  - OBJECTIVE: To examine the incidence, predictors, and consequences of harsh
      discipline in a sample of low-birth-weight children at 1 and 3 years of age.
      DESIGN: Analysis of data from the Infant Health and Development Program, an 8
      site randomized clinical trial of low-birth-weight infants. The sample for
      analysis consisted of 715 children who were 3 years of age. The independent
      measurements of primary interest were the mother's hitting and scolding of her
      child as disciplinary practice. Analyses were run separately for boys and girls.
      Bivariate and logistic analyses were used to examine the predictors of the
      mother's hitting and scolding behavior. Multivariate analysis of variance was
      used to examine the consequences of the mother's harsh discipline on a child's IQ
      measured at age 3 years. MAIN OUTCOME MEASURES: The mother's self-report of
      whether she used more than 1 physical punishment in the past week, as well as an
      observer's report from 2 home visits of whether the mother hit or scolded the
      child during the 2-hour home visit. In addition, the Stanford-Binet Intelligence
      Scale was used to examine the consequences of persistent harsh discipline on
      child well-being. RESULTS: Findings demonstrate child, maternal, and
      environmental factors that might aggravate a parent's use of corporal punishment.
      Boys received higher amounts of harsh discipline on all outcome measures. For
      boys, growing up in an impoverished home was predictive of the greater likelihood
      of receiving harsh punishment. Using IQ at age 3 years as the outcome measure,
      girls were found to be vulnerable to persistent harsh discipline and lack of
      maternal warmth. Maternal harsh discipline in a context of low maternal warmth
      was associated with IQ scores for girls that are 12 points lower than the IQ
      scores of girls who received low punishment and high warmth.

PMID- 9265879
TI  - Relationship of education to the racial gap in neonatal and postneonatal
      mortality.
AB  - OBJECTIVE: To examine the impact of education on race differences in neonatal and
      postneonatal mortality. METHODS: Data were from North Carolina's Linked Birth and
      Infant Death File for 1988 through 1993. The study population included 169,601
      African American births and 400,359 European American births, with 2606 and 3060
      deaths, respectively. Multiple logistic regression was used to assess the effects
      of race and education on neonatal and postneonatal mortality, adjusting for
      sociodemographic, lifestyle, and medical risk factors. RESULTS: Risks of death
      were higher for African Americans than for European Americans, more so in the
      neonatal than in the postneonatal period. Odds ratios (with 95% confidence
      intervals in parentheses) comparing African Americans to European Americans were
      as follows: neonatal deaths, 2.2 (1.9-2.5), 2.3 (2.1-2.6), and 2.8 (2.5-3.2) for
      less than 12, 12, and more than 12 years of education; and postneonatal deaths,
      1.3 (1.1-1.6), 1.5 (1.3-1.7), and 2.1 (1.7-2.6), respectively. The biggest gap
      was for deaths in the first day of life, with odds ratios ranging from 2.8 to
      3.6. Education had no impact on neonatal mortality in either race. Medical
      factors were more influential in the neonatal than in the postneonatal period,
      whereas environmental and social factors appeared to play a greater role in the
      postneonatal period. CONCLUSIONS: Racial differences in neonatal death are
      increasing and may be related to inequities in the provision of health care. The
      racial gap in the postneonatal period, although declining, has not disappeared
      and may be more related to environmental, social, and economic factors.

PMID- 9265880
TI  - A longitudinal magnetic resonance imaging study of brain changes in adolescents
      with anorexia nervosa.
AB  - OBJECTIVE: To assess whether the cerebral gray and white matter volume deficits
      described in patients with anorexia nervosa (AN) are fully reversible with weight
      rehabilitation. DESIGN: A prospective cohort study using magnetic resonance
      imaging to examine the brains of female adolescents after weight recovery from
      AN. SETTING: An adolescent eating disorder program located in a tertiary care
      children's hospital. PARTICIPANTS: Of 13 patients who underwent a previous
      magnetic resonance imaging study at a low weight, 6 patients were weight
      recovered and underwent rescanning. All brain measures were corrected for the
      effects of intracranial volume and age, based on a regression analysis of a group
      of 34 healthy female control subjects. Scans from the patients with AN were also
      compared with scans from an age-matched subset of 16 healthy female controls.
      MAIN OUTCOME MEASURES: White matter volumes, gray matter volumes, and
      cerebrospinal fluid volumes in the weight-recovered AN group. RESULTS:
      Quantitative analysis showed that white matter and ventricular cerebrospinal
      fluid volumes changed significantly (P = .03 for both) on weight recovery from
      AN. The weight-recovered patients had significant gray matter volume deficits (P
      = .01) and elevated cerebrospinal fluid volumes (P = .005) compared with those of
      the age-matched controls. They no longer had significant (P = .30) white matter
      volume deficits. CONCLUSION: The finding of persistent gray matter volume
      deficits in patients who have recovered their weight after AN suggests an
      irreversible component to the structural brain changes associated with AN, in
      addition to a component that resolves on weight recovery.

PMID- 9265881
TI  - Health insurance for low-income working families. Effect on the provision of
      immunizations to preschool-age children.
AB  - BACKGROUND: The out-of-pocket cost for immunizations is a cause for referral to
      public health department clinics and is associated with delayed immunization. In
      1991, New York State started Child Health Plus (CHPlus), an insurance program
      that covers ambulatory care and immunization services for children of families
      earning less than 222% of the poverty level. OBJECTIVE: To determine the effect
      of CHPlus on the provision of immunizations. DESIGN: A before-and-after design
      was used to compare the year immediately before enrollment in CHPlus with the
      first year after enrollment in CHPlus. A mixed-model analysis of variance was
      used to control for the effects of age. SETTING: All area primary care practices
      (n = 164) and public health department clinics (n = 6). SUBJECTS: Children (n =
      1730) younger than 6 years who were enrolled in CHPlus. MAIN OUTCOME MEASURES:
      Number of immunization visits; types of providers (public health department
      clinics or primary care providers [pediatricians and family physicians]); and
      series-complete immunization coverage, including the diphtheria toxoid, tetanus
      toxoid, and pertussis vaccine, the oral poliovirus vaccine, and the measles,
      mumps, and rubella vaccine. RESULTS: The average age of the children was 37.7
      months, 85% were white, 50% had been uninsured for immunizations before
      enrollment in CHPlus, and 16% previously received Medicaid. For infants, CHPlus
      decreased immunization visits to public health department clinics by 37% (from
      0.14 to 0.09 visits per child, P = .009), increased immunization visits to
      primary care providers' offices by 15% (from 2.3 to 2.7 visits per child, P =
      .001), and increased immunization coverage by 7% (from 76% to 83%, P = .03). For
      children aged 1 to 5 years, CHPlus decreased visits to public health department
      clinics by 67% (from 0.06 to 0.02 visits per child, P < .001), increased visits
      to primary care providers' offices by 27% (from 0.46 to 0.59 visits per child, P
      < .001), and increased immunization coverage by 5% (from 83% to 88%, P < .001).
      The effects were greatest among previously uninsured children and among those
      with a gap in insurance coverage that was longer than 6 months. CONCLUSIONS:
      Insurance coverage for low-income working families resulted in a shift in the
      provision of immunizations from the health department to primary care providers
      and in increased immunization coverage.

PMID- 9265882
TI  - Adolescent substance use and abuse.

PMID- 9265883
TI  - Parental knowledge and choice regarding live and inactivated poliovirus vaccines.
AB  - BACKGROUND: Concern about the 8 to 10 cases per year of vaccine-associated
      paralytic poliomyelitis caused by the live oral poliovirus vaccine (OPV) has led
      to revised guidelines for immunization of children in the United States. The use
      of inactivated poliovirus vaccine (IPV) at 2 and 4 months of age could require
      administration of 3 injections per visit until combination products are
      available. OBJECTIVE: To determine parents' knowledge of poliovirus vaccines and
      the choices they would make between IPV and OPV. METHODS: Parents of 240 children
      aged 2 weeks to 18 months under the care of 10 private pediatricians in the
      Baltimore, Md, metropolitan area were interviewed prior to the announcement of
      revised advisory committee guidelines. RESULTS: The majority (62.5%) of
      respondents were not aware that 2 poliovirus vaccines are available. After
      reviewing standardized information about the vaccines and 2 alternate schedules,
      most (75%) parents would consult someone (primarily their physician) before
      making a final choice of a vaccine schedule. If parents made the choice without
      consulting anyone else, 61.3% would choose to have their child receive IPV and 3
      injections per visit as compared with an all-OPV schedule and 2 injections per
      visit. Inactivated poliovirus vaccine was preferred by most parents because it
      would reduce the risk for vaccine-associated paralytic poliomyelitis. Oral
      poliovirus vaccine was preferred by 37.9% of parents primarily because it was
      given orally. If the number of injections at each visit was the same for both
      vaccines, 76.3% of parents would choose the IPV schedule, and if the number of
      injections was reduced to 2 by combining IPV with another vaccine, 87.9% of
      parents would choose IPV. CONCLUSION: The number of injections per visit is an
      important issue, but a majority of parents would choose to have their children
      receive extra injections to prevent the low risk for vaccine-associated paralytic
      poliomyelitis.

PMID- 9265884
TI  - Widespread growth retardation and variable growth recovery in foster children in
      the first year after initial placement.
AB  - OBJECTIVES: To determine children's growth patterns in the first year of foster
      care placement and to compare catch-up growth with initial height percentile as
      indicators of prior growth retardation. DESIGN: Inception cohort. SUBJECTS: Forty
      five children aged 1 1/2 to 6.0 years in their first year of foster care.
      SETTING: Urban, community-based primary care center. MAIN OUTCOME MEASURES:
      Height, weight, weight-for-height, and annual growth velocity z scores 1 year
      after placement. RESULTS: The group entered foster care with an overall height
      deficit (height z = -0.21), grew at an above-average rate (velocity z = +0.33),
      and eliminated the height deficit by the end of the year (height z = -0.02; P <
      .05). Weight increased (baseline weight z = -0.16; year-end weight z = +0.35) and
      correlated with height z change (r = 0.385, P = .009). Weight for expected weight
      for-height-age was above average and did not change (baseline weight for expected
      weight-for-height-age z = +0.30; year-end weight for expected weight-for-height
      age z = +0.40). Baseline age correlated with velocity z (r = .413, P = .005) but
      not with change in height z. Baseline height z did not correlate with either
      velocity z or change in height z. Three patterns of growth were seen: 21 (47%)
      showed catch-up growth (height velocity z = 1.34; gain in height z = +0.61); 16
      (36%) showed stable growth; and 8 (18%) showed poor growth (height velocity z = 
      1.49; decrease in height z = -0.49). CONCLUSIONS: Almost half of the children
      showed significant catch-up growth in the first year after foster care placement,
      indicating probable prior growth failure. Initial height was not predictive of
      future growth, and simple screening (such as height less than the fifth
      percentile) would have missed the majority of children who showed catch-up
      growth. A substantial minority (18%) continued to decline across height
      percentiles after placement. The initial and subsequent growth failure and catch
      up growth in this population did not appear to be related to nutritional changes.

PMID- 9265885
TI  - Shelter-based homeless youth. Health and access to care.
AB  - OBJECTIVES: To compare the self-reported risk-taking behaviors, health status,
      and access to care issues of 2 samples of shelter-based homeless youth who had
      previously been street youth (youth on streets or doubling-up with friends or
      lovers) and systems youth (youth involved in foster care) and to examine
      information on the etiology of homelessness, including parent or family of origin
      risk factors for both samples. DESIGN: The study population consisted of 109
      shelter-based homeless youth: 41 street youth and 68 systems youth. A chart audit
      was completed on all youth, noting documentation of past health problems, reasons
      for shelter placement, and parental risk factors. Adolescents from both samples
      completed a health history questionnaire followed by a physical examination.
      Differences between the 2 samples for behaviors and disease diagnoses were
      examined using chi 2 and 2-tailed t tests. RESULTS: The street youth exhibited
      greater risk-taking behaviors and suffered from poorer health status and access
      to care than did systems youth. The main differences were in substance using and
      high-risk sexual behaviors. The street youth were more likely to report previous
      exposure to violence and having been victims of forced sex. Self-reported risk
      behaviors, including sexual activity and substance abuse were corroborated by
      more objective information on these items from medical record information. The
      street youth were more likely to be medically uninsured, to have used an
      emergency department in the past year, and to have used an emergency department
      for their last care. CONCLUSIONS: There are important variations in health needs
      between samples of homeless youth, often overlooked in health planning for this
      population. Knowledge of parent or family of origin risk factors and causes of
      homelessness provides important contextual information for understanding the risk
      behaviors and health states of homeless youth.

PMID- 9265886
TI  - Strategies for managing group A streptococcal pharyngitis. A survey of board
      certified pediatricians.
AB  - OBJECTIVE: To assess the management strategies and knowledge of board-certified
      pediatricians regarding group A beta-hemolytic streptococcal (GABHS) pharyngitis.
      DESIGN: Survey of 1000 US pediatricians in 1991, chosen randomly from the
      membership of the American Academy of Pediatrics. The survey included questions
      related to 2 clinical scenarios, respondent demographics, and knowledge of
      streptococcal pharyngitis. SUBJECTS: Pediatricians who treated patients with
      pharyngitis. Of the 690 surveys that were returned, 510 pediatricians treated
      patients with pharyngitis and were included in the data analysis. DATA ANALYSIS:
      Data were analyzed using Chi 2 statistics for categorical data and the Student t
      test for continuous variables. RESULTS: Antigen detection tests (ADTs) were used
      by 64% of the pediatricians; 85% used throat cultures. Strategies for diagnosing
      streptococcal pharyngitis were throat culture alone (38%), consider positive ADTs
      definitive and use throat culture when ADTs are negative (42%), ADT alone (13%),
      ADT and throat culture for all patients with pharyngitis (5%), and no tests for
      GABHS performed (2%). Thirty-one percent usually or always treated with
      antibiotics before test results were available. Only 29% of these "early
      treaters" always discontinued antibiotics when tests did not confirm the presence
      of group A streptococci. The drug of choice for treatment was penicillin (73%);
      another 26% preferred a derivative of penicillin, particularly amoxicillin. Many
      pediatricians altered their management when a patient had recurrent streptococcal
      pharyngitis. Nearly half of the respondents would use a different antibiotic than
      they used for routine acute streptococcal pharyngitis. They most often changed to
      erythromycin (25%), cefadroxil (23%), or amoxicillin-clavulanate (20%). Follow-up
      throat culture was obtained by 51% of pediatricians after treatment of recurrent
      streptococcal pharyngitis. A patient with chronic carriage of GABHS and symptoms
      of pharyngitis would be treated with an antibiotic by 84%; most (62%) would use a
      penicillin. Other choices were cephalosporins (19%), erythromycin (12%),
      clindamycin (3%), or rifampin plus penicillin (3%). Tonsillectomy was recommended
      for symptomatic carriers by 31% of respondents. Carriers without symptoms were
      less likely to be treated with antibiotics (23%) or referred for tonsillectomy
      (21%). CONCLUSIONS: Most surveyed board-certified pediatricians managed acute
      GABHS pharyngitis appropriately, but 15% to 20% used diagnostic or treatment
      strategies that are not recommended. There was lack of a consensus about the
      management of recurrent GABHS pharyngitis and chronic carriage of GABHS.

PMID- 9265887
TI  - Water supplementation of infants in the first month of life.
AB  - OBJECTIVE: To describe the prevalence of and risk factors associated with regular
      water supplementation of neonates. DESIGN: Evaluation of data from the Food and
      Drug Administration's Infant Feeding Practices Study, a panel study of US women
      of fairly high socioeconomic status who were followed up from late pregnancy
      through their infants' first year of life. The sample was drawn from a nationally
      distributed consumer mail panel. Each mother was asked whether she gave her
      neonate water at least 3 times per week. PARTICIPANTS: A total of 1677 mothers of
      infants who were neonates in April through November 1993. MAIN OUTCOME MEASURES:
      Percentages of mothers who gave their neonates water at least 3 times a week,
      considering infant feeding status, mother's education, and family income.
      RESULTS: About one fourth (24.7%) of the mothers reported giving their neonates
      water at least 3 times per week. Stratification by feeding practices and
      socioeconomic factors revealed that 41.6% of mothers who formula-fed their
      neonates, 47.4% of mothers with less than a high school education, and 35.4% of
      mothers with an annual family income less than $22,500 gave their neonates water
      at least 3 times per week. CONCLUSIONS: Water supplementation of neonates was a
      prevalent practice in this cohort of women. Feeding practices, maternal
      education, and family income were all significant risk factors associated with
      this behavior.

PMID- 9265888
TI  - Adolescent vegetarians. A behavioral profile of a school-based population in
      Minnesota.
AB  - OBJECTIVE: To compare a population-based sample of vegetarian and nonvegetarian
      adolescents regarding food intake patterns, disordered eating, and a range of
      other non-food-related health-compromising and health-promoting behaviors.
      DESIGN: A cross-sectional school-based survey. SETTING: Public schools within
      nonurban areas of Minnesota. PARTICIPANTS: Adolescents (n = 107) aged 12 to 20
      years who reported on the Minnesota Adolescent Health Survey that they follow a
      vegetarian diet and a comparison group of nonvegetarian youth (n = 214) matched
      for sex, age, and ethnicity. The percentage of self-identified vegetarians in the
      study population was relatively low (0.6%); most of the vegetarians were female
      (81%). MAIN OUTCOME MEASURES: Food intake patterns, disordered eating (frequent
      dieting, binge eating, self-induced vomiting, and laxative use), health
      compromising behaviors (tobacco, alcohol, and marijuana use and suicide
      attempts), and health-promoting behaviors (seat belt use, physical activity, and
      brushing teeth regularly). RESULTS: Vegetarian adolescents were twice as likely
      to consume fruits and vegetables (P < .001), one third as likely to consume
      sweets (P < .001), and one fourth as likely to eat salty snack foods (P < .001)
      more than once a day compared with nonvegetarians. Vegetarians were almost twice
      as likely to report frequent dieting (P < .001), 4 times as likely to report
      intentional vomiting (P < .001), and 8 times as likely to report laxative use (P
      < .001) than nonvegetarians. Overall, associations with other health-compromising
      and health-promoting behaviors were not apparent. CONCLUSIONS: A vegetarian diet
      may be beneficial because of increased fruit and vegetable consumption and
      decreased consumption of foods high in fat, salt, and sugar. However, adolescents
      following a vegetarian diet need to be screened for adequate food intake and
      potential disordered eating behaviors.

PMID- 9265889
TI  - A methodology to maximize resident input in improving a pediatric rotation.
AB  - OBJECTIVE: To develop a structured process to gain resident input into the
      improvement of their educational experience by (1) taking a small amount of
      resident time and effort, (2) fostering the generation of new ideas, (3) allowing
      the prioritization of ideas, (4) generating implementation plans for the ideas,
      and (5) offering the participants relative anonymity. DESIGN: Cross-sectional
      survey and group sessions. SETTING: Urban, university-based children's hospital.
      PARTICIPANTS: Members of the pediatric residency program in the 1993-1994
      academic year. INTERVENTIONS AND RESULTS: The process was piloted for an
      emergency department rotation and borrows aspects of the Delphi Technique,
      Nominal Group Technique, and focus group methods. A survey regarding an emergency
      department rotation was distributed to all pediatric residents, and the 10 most
      commonly noted problems were compiled. These problems were brought to group
      sessions held for each level of training. Problems not listed were added if they
      were mentioned during the session; however, no problem was removed from the list.
      The sessions, designed to offer relative anonymity to the residents, included an
      initial clarification period, a round-robin prioritization of ideas, and an open
      discussion designed to generate solutions. Resident-generated solutions resulting
      from the group sessions were reviewed by the attending staff, and changes were
      implemented during the next year. CONCLUSION: The technique that we developed is
      a practical and time-efficient method of incorporating resident perspectives into
      the improvement of a rotation.

PMID- 9265890
TI  - Radiological case of the month. Candida meningitis in a low-birth-weight infant.

PMID- 9265891
TI  - Radiological case of the month. Posttraumatic pseudocysts.

PMID- 9265892
TI  - Picture of the month. Tuberculous dactylitis.

PMID- 9265894
TI  - Pathological case of the month. Helicobacter pylori gastritis.

PMID- 9265893
TI  - Pathological case of the month. Meconium periorchitis.

PMID- 9265895
TI  - A pediatric perspective on medical necessity.

PMID- 9265896
TI  - Thrombocytosis in sickle cell anemia.

PMID- 9265897
TI  - Liver diseases and the clinical laboratory--the Twentieth Arnold O. Beckman
      Conference in Clinical Chemistry.

PMID- 9265898
TI  - Molecular biological methods in diagnosis and treatment of liver diseases.
AB  - Molecular biology is making a tremendous impact on the diagnosis and treatment of
      liver diseases. Methods such as the polymerase chain reaction are changing the
      way physicians diagnose and monitor patients with viral hepatitis. Assays based
      on recombinant protein antigens allow for detection of specific autoantibodies in
      diseases such as primary biliary cirrhosis. The diagnosis of inherited metabolic
      diseases, such as hemochromatosis and Wilson disease, is being revolutionized by
      discovery of the defective genes involved and the development of methods to
      rapidly sequence DNA and identify mutations. Treatments and preventive measures
      are now possible with use of drugs and vaccines produced by recombinant DNA
      technology. Gene therapy and nucleic acid-based therapeutics are also realistic
      future treatment options for individuals with liver diseases.

PMID- 9265899
TI  - History of posttransfusion hepatitis.
AB  - The risk of hepatitis virus transmission from tranfusions has declined
      dramatically from that of the 1940s when posttransfusion hepatitis (PTH) was
      first appreciated. Introduction of hepatitis B surface antigen screening and
      conversion to volunteer donors for whole-blood donations in the late 1960s and
      early 1970s led to substantial reduction in PTH cases. However, up to 10% of the
      recipients continued to develop PTH, most cases of which were attributed to an
      unknown non-A, non-B viral agent. Implementation of surrogate marker testing
      (i.e., alanine aminotransferase and anti-hepatitis B virus core antigen) for
      residual non-A, non-B hepatitis in the late 1980s reduced the per unit risk of
      PTH from 1 in 200 to about 1 in 400. Hepatitis C virus was discovered in 1989 and
      quickly was established as the causative agent of > 90% of non-A, non-B PTH.
      Introduction of progressively improved antibody assays in the early 1990s reduced
      the risk of PTH due to hepatitis C virus to about 1 in 100000. Although
      additional hepatitis viruses exist (e.g., hepatitis G virus), these appear to be
      minor contributors to clinical PTH, which has been virtually eradicated.

PMID- 9265900
TI  - Type A viral hepatitis: epidemiology, diagnosis, and prevention.
AB  - Hepatitis A virus (HAV) infection occurs worldwide and is an important cause of
      acute viral hepatitis in the US. In this review, I cover the epidemiology, course
      of infection, clinical manifestations, serological responses, and prevention of
      this infection. Although most patients completely recover from this disease,
      elderly patients have a substantial mortality risk. Recently licensed vaccines
      are highly efficacious.

PMID- 9265901
TI  - Hepatitis B: diagnosis, prevention, and treatment.
AB  - Hepatitis B virus (HBV) infection occurs worldwide and is an important cause of
      acute and chronic viral hepatitis in the US. In this review, I describe the
      virus, risk factors for infection, clinical features of infection, results of
      laboratory tests during infection, and standard and emerging treatment for
      chronic infection. Although 95% of adult patients recover completely from HBV
      infection, 90% of children < or = 4 years of age develop chronic infection.
      Active vaccination is highly efficacious.

PMID- 9265902
TI  - Hepatitis C--diagnosis and monitoring.
AB  - Cloning of the hepatitis C virus (HCV) genome was a tremendous advance in the
      development of tests for diagnosis and monitoring of HCV-infected patients.
      Serological tests, including enzyme-linked immunoassays and RIBA strip immunoblot
      assays, are primarily used to screen blood donations and to diagnose and confirm
      HCV infection. Tests for HCV RNA, including polymerase chain reaction (PCR)-based
      assays and the branched-DNA (bDNA) assay, are used for therapeutic monitoring and
      prognostics. Here, we present the development and future potential of these
      diagnostic tests. We also provide examples of how these tests are used to follow
      the progression of disease, select and adjust treatment protocols, and evaluate
      the efficacy of therapeutic regimens.

PMID- 9265903
TI  - Xenobiotic-induced hepatotoxicity: mechanisms of liver injury and methods of
      monitoring hepatic function.
AB  - Xenobiotic-induced liver injury is a clinically important etiology of hepatic
      disease that, if not recognized, can lead to hepatic failure. In this article we
      discuss the mechanisms of xenobiotic-induced liver injury, various factors that
      can alter the risk and severity of injury, the clinical and laboratory
      manifestations of injury, and the methods used to detect the presence of injury
      and (or) functioning liver mass.

PMID- 9265904
TI  - Fatty acid ethyl esters: short-term and long-term serum markers of ethanol
      intake.
AB  - This review includes a description of short-term and long-term markers of ethanol
      intake and their clinical utility. The major portion of this report is a summary
      of studies on fatty acid ethyl ester, a new marker for monitoring both acute and
      chronic ethanol intake. With the markers described in the review, algorithms to
      assess recent ethanol intake, chronic ethanol intake, and end organ damage are
      included to provide a practical approach to the evaluation of the patient.

PMID- 9265905
TI  - Mild liver enzyme abnormalities: eliminating hemochromatosis as cause.
AB  - Chronic mild liver enzyme abnormalities are attributable to hereditary
      hemochromatosis in at least 3% of cases. Hemochromatosis formerly was diagnosed
      late with diabetes and hepatic and cardiac failure. Only recently have the
      autosomal recessive inheritance and subtle early presentations been understood.
      However, patients still wait many years and see many physicians before receiving
      a correct diagnosis. Increased serum transferrin saturation is currently the best
      test for detection of those likely to accumulate iron. Serum ferritin identifies
      those requiring treatment. When liver biopsy (controversial in asymptomatic
      individuals) is indicated, chemical measurement of liver iron content is helpful
      and therapeutic phlebotomy is the only effective treatment. Caucasian-type
      hemochromatosis (prevalence of 0.005) is associated with genetic abnormalities in
      HLA-H but also occurs in other ethnic groups. Those of African descent may have a
      different but also heritable iron-loading disease. Caucasian-type and to a lesser
      extent African iron loading are detectable early by laboratory testing. Early
      treatment restores normal expectations of length and quality of life in the
      Caucasian disease. Long-term treatment data are not yet available in African iron
      loading. Laboratory-initiated screening programs using unsaturated iron-binding
      capacity can eliminate symptomatic hemochromatosis.

PMID- 9265906
TI  - Assessment of liver function: pre- and peritransplant evaluation.
AB  - Liver transplantation has been demonstrated to be a successful therapeutic
      modality for patients with end-stage liver disease. The high rate of survival for
      an otherwise terminal condition has resulted in significant expansion of the
      indications and diseases treated by this procedure, and is hampered only by the
      limited numbers of organs available for transplantation. Efforts in clinical and
      laboratory medicine should be directed to identify candidates who would benefit
      most from this procedure, to provide better means for accurate assessment of
      liver reserve and the appropriate timing for transplantation, to identify quality
      liver grafts that would have the potential to tolerate cold preservation and
      reperfusion injury, and to assist in accurate monitoring of graft function
      immediately after transplantation. The aim of this manuscript is to describe the
      existing pathways for clinical and laboratory assessment of pretransplant
      residual liver function, the donor liver graft, and immediate posttransplantation
      function.

PMID- 9265907
TI  - Clinical chemistry and post-liver-transplant monitoring.
AB  - Liver transplantation is an accepted therapy for end-stage liver disease. After
      allografting, a variety of clinical problems may require laboratory involvement
      for accurate and timely diagnosis and intervention. Critical factors in the
      choice of a laboratory test menu to support a transplant program include
      turnaround times that support clinical decisionmaking, real diagnostic value, and
      real value for money. Particular clinical problems, whose early presentation must
      be anticipated, include graft ischemia, primary nonfunction, and hepatic artery
      thrombosis. Acute rejection is common at 5-10 days posttransplantation, the
      principal target being the biliary tree. Longer-term problems are associated with
      the therapeutic drug measurement of cyclosporin A and, increasingly, tacrolimus
      (FK506); the side effects of immunosuppressant therapy also require monitoring. A
      successful liver transplant program can be adequately supported with a simple
      battery of automated tests that are cheap, fast, and available at all times.

PMID- 9265908
TI  - Diagnostic strategies and test algorithms in liver disease.
AB  - As clinicians evaluate patients, they first develop problem lists based on the
      history, physical examination, and basic laboratory studies. Synthesis and
      analysis result in a differential diagnosis with associated disease
      probabilities. Experienced clinicians then selectively use diagnostic tests to
      rule in or rule out these possibilities. For example, in a patient presenting
      with jaundice, anorexia, fever, and abdominal pain, the relative increases of the
      serum aminotransferase activity and the serum alkaline phosphatase will help to
      guide the subsequent evaluation. If the aminotransferase activity is markedly
      increase, then the subsequent evaluation will be targeted toward identifying an
      etiology for hepatocellular injury. In contrast, if the alkaline phosphatase is
      markedly increased, then the evaluation would be targeted toward identifying an
      etiology for obstructive jaundice. This paper reviews clinical decision making,
      discusses characteristics of diagnostic tests, and presents examples of how basic
      clinical information can guide the use of the laboratory in evaluating patients
      with suspected liver disease.

PMID- 9265909
TI  - The application of neuroimaging techniques to drug development.
AB  - Neuroimaging is a powerful and innovative tool for studying the pathology of
      psychiatric diseases and, more recently, for studying the drugs used in their
      treatment. Technological advances in imaging have made it possible to
      noninvasively extract information from the human brain regarding a drug's
      mechanism and site of action. Until now, our understanding of human brain
      pharmacology has depended primarily on indirect assessments or models derived
      from animal studies. However, the advent of multiple techniques for human brain
      imaging allows researchers to focus directly on human pharmacology and brain
      function. This review outlines available neuroimaging techniques and examines how
      these various methods have already been applied to the drug development process,
      as well as how they might be applied in the future.

PMID- 9265910
TI  - Efficacy of olanzapine: an overview of pivotal clinical trials.
AB  - Olanzapine is a new "atypical" antipsychotic agent that belongs chemically to the
      thienobenzodiazepine class. Its relatively greater binding affinity for 5-HT2
      compared to D2 receptors makes it similar to the atypical agent clozapine, a
      serotonin/dopamine antagonist. Four double-blind pivotal studies, which compare
      olanzapine to placebo and/or haloperidol, are presented. The results suggest that
      olanzapine is as effective as haloperidol for positive symptoms and more
      effective than haloperidol for the treatment of the negative symptoms of
      schizophrenia.

PMID- 9265911
TI  - Safety of olanzapine.
AB  - Clinical safety data for treatment of acute schizophrenia with olanzapine, a new
      atypical antipsychotic agent, are summarized. The primary clinical trial safety
      database included 2500 patients treated with olanzapine, 810 with haloperidol,
      and 236 with placebo. The overall discontinuation rate from olanzapine treatment
      was low. Significant adverse events included somnolence, weight gain, and
      asymptomatic treatment-emergent transaminase elevation. Minimal parkinsonism and
      akathisia with rare dystonia were noted. No hematotoxicity was noted. The
      incidence of seizures and sexual dysfunction was rare.

PMID- 9265912
TI  - Olanzapine and the new generation of antipsychotic agents: patterns of use.
AB  - As the new generation of atypical antipsychotics becomes available, the
      limitations of the older typical agents become apparent. The new medications,
      which have benefits other than the alleviation of positive symptoms of
      schizophrenia, may also be beneficial for psychotic disorders that have responded
      poorly to conventional neuroleptics. This article will describe the potential use
      of the atypical antipsychotics, especially olanzapine, for affective mood
      disturbances in schizophrenia, psychotic depression and mania, first-break
      schizophrenia, comorbid schizophrenia and substance abuse disorders, dementia in
      the elderly and those with late-onset schizophrenia, and behavioral problems in
      patients with mental retardation or developmental delays.

PMID- 9265913
TI  - The biological basis of schizophrenia: new directions.
AB  - The desire to understand the pathophysiology of schizophrenia has inspired an
      explosion in research over the past decade. This review highlights some key
      studies that have led to fundamental changes in our understanding of this
      disorder, focusing on the search for genes in schizophrenia, as well as several
      recent alternatives to the original dopamine hypothesis of schizophrenia.
      Advances in genetic methodology have allowed schizophrenia researchers to conduct
      genome-wide searches for susceptibility genes. Although these studies have
      identified several regions that demonstrate potential linkage with schizophrenia,
      a definitive genetic cause has not yet been proved. Recent neurochemical
      hypotheses have focused on the cortical amino acid neurotransmitter systems
      (i.e., glutamate and GABA), while anatomical studies suggesting abnormal brain
      development and premorbid functional deficits have led some researchers to
      propose a neurodevelopmental origin for schizophrenia. A sizable database can be
      marshaled in support of each of these ideas, but none as yet fully explain the
      biological basis of schizophrenia.

PMID- 9265914
TI  - In vitro and in vivo biochemistry of olanzapine: a novel, atypical antipsychotic
      drug.
AB  - BACKGROUND: Classical (typical) antipsychotic drugs are in wide use clinically,
      but some patients do not respond at all to treatment, while in others, negative
      symptoms and cognitive deficits fail to respond. Also, these drugs often cause
      serious motor disturbances. Clozapine, an atypical antipsychotic, appears to
      correct many of these deficiencies, but has a significant incidence of
      potentially fatal agranulocytosis. Accordingly, we attempted to develop a
      prototype of a new generation of antipsychotics that is both more efficacious and
      safe. Our strategy was to create a compound that is not only active in behavioral
      tests that predict antipsychotic action but also shares the rich, multifaceted
      receptor pharmacology of clozapine without its side effects. To this end, Eli
      Lilly and Co. developed olanzapine. In this article we characterize the in vitro
      and in vivo receptor pharmacology of olanzapine. METHOD: We evaluated olanzapine
      interactions with neuronal receptors using standard assays of radioreceptor
      binding in vitro and well-established in vivo (functional) assays. RESULTS:
      Binding studies showed that olanzapine interacts with key receptors of interest
      in schizophrenia, having a nanomolar affinity for dopaminergic, serotonergic,
      alpha 1-adrenergic, and muscarinic receptors. In vivo olanzapine is a potent
      antagonist at DA receptors (DOPAC levels; pergolide-stimulated increases in
      plasma corticosterone) and 5-HT receptors (quipazine-stimulated increases in
      corticosterone), but is weaker at alpha-adrenergic and muscarinic receptors.
      Olanzapine has little or no effect at other receptors, enzymes, or key proteins
      in neuronal function. Olanzapine has a receptor profile that is similar to that
      of clozapine: it is relatively nonselective at dopamine receptor subtypes and it
      shows selectivity for mesolimbic and mesocortical over striatal dopamine tracts
      (electrophysiology; Fos). CONCLUSION: The binding and functional profile of
      olanzapine (1) is similar to that of clozapine, (2) indicates that olanzapine is
      an atypical antipsychotic drug, and (3) is consistent with clinical efficacy. If
      olanzapine also proves to be safe, then it will have high potential to become a
      more ideal antipsychotic drug.

PMID- 9265915
TI  - Behavioral pharmacology of olanzapine: a novel antipsychotic drug.
AB  - BACKGROUND: In this paper, we review the behavioral pharmacology of olanzapine
      and compare it to its in vitro profile and to clozapine and a number of other
      antipsychotic agents, and we estimate the likelihood that olanzapine will be an
      effective and safe antipsychotic with fewer side effects. METHOD: Since there is
      no model of schizophrenia, per se, a battery of behavioral assays was used.
      RESULTS: Behavioral assays confirmed the in vitro results that olanzapine
      interacts with dopamine, serotonin, and muscarinic receptor subtypes. Moreover,
      olanzapine appears to have a clozapine-like atypical profile based on (1)
      mesolimbic selectivity, (2) blocking 5-HT receptors at a lower dose than dopamine
      receptors, and (3) inhibiting the conditioned avoidance response (indicative of
      antipsychotic efficacy) at doses that are lower than those required to induce
      catalepsy (indicative of extrapyramidal side effects). No only is this profile
      similar to that of clozapine, but olanzapine has other similarities: olanzapine
      substitutes for clozapine in a drug discrimination assay; like clozapine and
      unlike "typical" antipsychotics, olanzapine increases responding in a conflict
      procedure; and olanzapine, like clozapine, reverses changes induced by
      antagonists of the NMDA receptor. CONCLUSION: On the basis of these findings, we
      predict that olanzapine will be an efficacious antipsychotic, active against both
      positive and negative symptoms, while producing fewer extrapyramidal symptoms
      than existing treatments.

PMID- 9265916
TI  - Dosing the antipsychotic medication olanzapine.
AB  - Olanzapine is a new antipsychotic agent with serotonin/dopamine antagonism
      action. Efficacy in treating overall psychopathology in acute schizophrenia as
      measured by the BPRS0-6 total score was demonstrated at 10 mg/day versus placebo;
      at doses in a 5-20 mg/day range, olanzapine was comparable or superior to
      haloperidol. Superior efficacy for negative and depressive symptoms was shown in
      comparison to haloperidol. Olanzapine has a favorable acute and tardive
      extrapyramidal symptom profile relative to haloperidol and caused substantially
      less elevation of serum prolactin. Dose-related weight gain and asymptomatic mild
      transaminase elevations occurred in olanzapine-treated patients.

PMID- 9265917
TI  - Pharmacoeconomic evaluation of antipsychotic therapy for schizophrenia.
AB  - Medications comprise a minor portion of the costs of schizophrenia, but may have
      a major impact on the likelihood of successful outcome of care. Novel
      antipsychotic medications which demonstrate superior symptom control, an improved
      safety profile, and benefits to quality-of-life may also reduce patients' need
      for medical services and the associated costs of these treatments. This report
      first considers key experimental design elements involved in integrating
      pharmacoeconomic and clinical objectives in studies of new drug therapies for
      schizophrenia. We briefly discuss the choice of therapies for comparison,
      randomization and blinding, sample size and composition, data collection,
      selection of the time frame for economic evaluation, and the importance of an
      intent-to-treat perspective. Second, as an example we present the design and
      selected results from a new economic clinical trial of the novel antipsychotic
      olanzapine. This trial utilized a randomized, double-blind design to compare the
      use of medical services and the cost of treatment for 817 schizophrenic patients
      from the United States treated with olanzapine or haloperidol. In comprehensive
      health care cost comparisons that incorporated the expenditures for study
      medications, the total cost of health care for olanzapine-treated patients was
      reduced by an average of $431 per month in comparison with haloperidol-treated
      patients during the initial 6 weeks of treatment. Among treatment responders
      receiving double-blind therapy for a maximum of 1 year, the total cost of care
      among olanzapine responders was reduced by an average of $345 per month in
      comparison with haloperidol responders. The results of this economic evaluation
      suggest that olanzapine's superior treatment profile may lead to reductions in
      the overall costs of medical care for patients with schizophrenia.

PMID- 9265918
TI  - The relationship of pharmacology to side effects.
AB  - Most traditional neuroleptics have a narrow therapeutic-to-toxic index, and thus,
      the novel antipsychotics are the result of a search to substantially widen the
      distance between the dose that treats psychosis and the one that produces adverse
      effects. In vitro binding profiles have been created for the atypical
      antipsychotics that have been approved by the U.S. Food and Drug Administration
      (FDA)-clozapine, olanzapine, and risperidone and those that are under FDA review
      quetiapine and sertindole. These profiles, which were compared with that of the
      typical neuroleptic haloperidol, provide guidance for predicting the adverse
      effects produced by these drugs. Most conventional antipsychotics have central
      nervous system effects, particularly extrapyramidal symptoms (EPS) and tardive
      dyskinesia, sedation, and dulling of cognition. Other adverse effects of the
      typical antipsychotics include the neuroleptic malignant syndrome, orthostatic
      hypotension, changes in liver function, anticholinergic and antiadrenergic side
      effects, sexual dysfunction, and weight gain. The newer agents have a lower
      incidence of EPS and tardive dyskinesia, while weight gain and changes in blood
      pressure and liver function tests are adverse effects that have been associated
      with the use of the newer agents. The favorable side effect profile of these new
      antipsychotics is likely to make patients more willing to continue treatment, and
      thus these agents represent a step forward in the treatment of patients with
      severe, chronic mental illness.

PMID- 9265920
TI  - Calculated versus measured oxygen consumption during and after cardiac surgery.
      Is it possible to estimate lung oxygen consumption?
AB  - BACKGROUND: Lung tissue is metabolically active and consumes oxygen. The oxygen
      content difference between arterial and mixed venous blood does not include the
      effect of pulmonary tissue oxygen uptake. Thus, oxygen consumption (VO2) of the
      lung should be reflected as a difference between VO2 measured by gas exchange and
      VO2 derived by the Fick principle. The purpose of this study was to measure in
      clinical conditions this difference (taken to represent the VO2 of the lung), and
      to evaluate the sources of error in lung VO2 estimation. METHODS: Nine patients
      undergoing coronary artery bypass grafting were studied. VO2 was measured by
      indirect calorimetry (VO2gasex) and compared to Fick-derived VO2 (VO2Fick) after
      induction of anaesthesia, after closure of the chest, at admission to intensive
      care, after stabilization of haemodynamics and during weaning from mechanical
      ventilation. The Fick-derived VO2 was calculated from blood samples taken at the
      beginning and at the end of each 20 min measurement period, and the mean of 12
      consecutive thermodilution cardiac output measurements taken during each 20 min
      measurement period. RESULTS: VO2gasex was higher than VO2Fick (P < 0.01; in all
      except 4 of 45 measurements). The difference between the measured and the
      calculated VO2 was 33 +/- 25 ml/min (mean +/- SD, range -16-100 ml/min). This
      difference represented 14 +/- 3% (range 11-18%) of the whole body VO2. The VO2
      difference was highest after the induction of anaesthesia (50 +/- 19 ml/min;
      range 20-41 ml/min, P < 0.03) and lowest on arrival at the intensive care unit
      (10 +/- 16 ml/min; range -16-39 ml/min). Core temperature did not correlate with
      the oxygen consumption difference. CONCLUSIONS: A constant difference between
      measured and calculated VO2 can be detected in carefully controlled clinical
      conditions. The difference between the two methods is due to both lung oxygen
      consumption and errors in the measurement of VO2 thermodilution cardiac output,
      haemoglobin and blood oxygen contents. We suggest that the perioperative changes
      of the VO2-difference are due not only to variation of the measurements but also
      to changes in lung metabolic activity.

PMID- 9265919
TI  - Switching antipsychotic medications.
AB  - Compared with conventional antipsychotics, the so-called "atypical"
      antipsychotics promise improved side effect profiles and better control of the
      symptoms of schizophrenia. Therefore, most patients currently taking conventional
      antipsychotics could potentially benefit from a switch to an atypical
      antipsychotic. Often, the key issue in deciding whether to switch is the presence
      of countervailing factors that mitigate against the change. This paper discusses
      the indications and contraindications for switching antipsychotics, plus issues
      that require consideration before a switch is made. Also, the advantages and
      disadvantages of various switching techniques are discussed, with a particular
      focus on the newer antipsychotic olanzapine.

PMID- 9265921
TI  - Relationship between intra- and postoperative oxygen transport and prolonged
      intensive care after cardiac surgery: a prospective study.
AB  - BACKGROUND: Prolonged intensive care is a rare but serious complication of
      cardiac surgery. It is required in less than 10% of operated patients but they
      use more than 30% of all the intensive care resources needed for cardiac surgery.
      The aim of our study was to describe the clinical course of the patients who need
      prolonged intensive care following cardiac surgery and to assess whether the
      intra- and postoperative oxygen transport variables are different in these
      patients as compared to patients with an uncomplicated course. METHODS: The study
      patients were divided into two groups according to the length of stay in the
      intensive care unit (ICU) after the operation: Group I, n = 241, ICU-stay < 5
      days and Group II, n 20, ICU-stay > or = 5 days. Hemodynamic and oxygen transport
      data were prospectively obtained intra- and postoperatively and postoperative
      organ dysfunctions were recorded. RESULTS: The patients in the prolonged
      intensive care group tended to be older, have lower ejection fraction and longer
      cardiopulmonary bypass time. Postoperatively, this group had significantly
      increased oxygen extraction rate (P = 0.035, repeated measures for ANOVA). In the
      logistic regression analysis, increased oxygen extraction (31% in Group I vs. 36%
      in Group II, P < 0.005) at 6 hours after arrival at the intensive care unit had
      the strongest independent association with the need for prolonged intensive care.
      CONCLUSIONS: There was no significant relationship between the factors
      conventionally assumed to be risk factors for prolonged intensive care. Instead,
      an increase in whole body oxygen extraction, reflecting a mismatch between the
      whole body oxygen demand and supply, was associated with the need for prolonged
      intensive care. Oxygen extraction increased to compensate for the reduced oxygen
      delivery, which in turn was caused by a lower arterial oxygen content.

PMID- 9265922
TI  - Uptake of inhaled nitric oxide in acute lung injury.
AB  - BACKGROUND: Despite the widespread use of inhaled nitric oxide (NO), little is
      known of its pulmonary uptake in patients with acute respiratory failure.
      METHODS: Fourteen patients with acute lung injury (ALI) and ongoing NO therapy
      were studied. Three doses of NO (5, 10 and 40 ppm) were given for 20 min and at
      each dose level the following parameters were recorded: minute ventilation,
      inspiratory NO conc., mixed expired NO conc., end-tidal NO conc., mixed expired
      CO2 conc., end-tidal CO2 conc, and arterial CO2 tension. Total uptake was
      calculated and correlated to the total amount of NO inhaled, the amount of NO
      administered to the alveolar space, and the amount of NO administered to the
      perfused alveolar space. RESULTS: About 35% of the total amount of NO delivered
      is taken up by the lungs, 70% of NO administered to the alveolar space is taken
      up, and 95-100% of the NO administered to perfused alveolar space is taken up.
      The size of the alveolar dead space varied between 10 and 60% of the alveolar
      space. At 40 ppm of inhaled NO there was no difference between inspired and mixed
      expired NO2 concentration, indicating that there is no significant NO2 formation
      taking place in the lungs during NO inhalation at the concentrations studied.
      CONCLUSIONS: Practically all NO administered to the perfused alveolar space is
      taken up. The total uptake differs from that of healthy persons probably because
      of differences in the alveolar dead space.

PMID- 9265923
TI  - Vitamin A exerts potential therapeutic effects in the endotoxaemic pig.
AB  - BACKGROUND: Pretreatment with an injection of vitamin A has beneficial effects on
      cardiac and pulmonary functions in normally bred endotoxaemic pigs. The present
      study was performed in order to elucidate whether the response of an ongoing
      infusion of E. coli can be modulated by a single injection of vitamin A. METHODS:
      Sixteen healthy (not vitamin A-depleted) pigs were anaesthetized, monitored,
      mechanically ventilated and subjected to an infusion of E. coli endotoxin (10
      micrograms.kg-1.h-1). This infusion resulted within 30 min in a progressive
      haemodynamic derangement. When the mean pressure in the pulmonary artery was
      twice the baseline value, vitamin A (460 IU.kg-1) or a corresponding volume of
      vehicle was injected intravenously. After sacrificing the animals, the right lung
      was excised and weighed, and biopsy specimens were taken from the left lung for
      microscopical examination. RESULTS: Mean arterial blood pressure was
      significantly less affected (P < 0.01) between the 1st and 6th hour in
      endotoxaemic pigs treated with vitamin A than in those given vehicle. The mean
      lung weight in the vitamin A-treated pigs was significantly lower than that in
      the vehicle group (164 +/- 5.3 vs 199 +/- 19.8 g; P < 0.01). Microscopical
      examination showed significantly less oedema (0.93 +/- 0.17 vs 2.00 +/- 0.26; P <
      0.01) and microatelectasis (0.56 +/- 0.17 vs 1.75 +/- 0.31; P < 0.01) in the
      vitamin A group. Endotoxaemia was also accompanied by an initial, steep decline
      in neutrophil counts in all animals; this decrease was significantly less
      pronounced (P < 0.05) in vitamin A-injected pigs than in the vehicle-injected
      group. The major difference was a more rapid restitution in the vitamin A group.
      CONCLUSION: Several manifestations of endotoxaemia were expressed less in the
      vitamin A group. Thus, vitamin A may turn out to be a tool in the management of
      endotoxaemia.

PMID- 9265924
TI  - Hemodynamic and coronary vascular effects of dexmedetomidine in the anesthetized
      goat.
AB  - BACKGROUND: In phase III trials, the hemodynamic stabilising effect of the alpha
      2-adrenergic agonist dexmedetomidine (DEX) is being investigated in patients with
      coronary artery disease, Coronary vascular effects of alpha 2-agonists have been
      studied in dogs and pigs, but both species have a different hemodynamic response
      to DEX than man. The aim of this study was to investigate the hemodynamic and
      coronary vascular effects in goats. METHODS: In 6 open-chest goats anesthetized
      with halothane, central and coronary hemodynamics and oxygen supply and demand
      were measured before and following IV bolus infusion of DEX in doses ranging from
      0.1 to 10 micrograms/kg. RESULTS: With DEX doses of 1 microgram/kg or higher,
      mean arterial pressure (MAP), systemic vascular resistance, coronary vascular
      resistance and arterio-mixed venous oxygen content increased within 2 min, but
      returned to baseline within 15 min. In contrast, there was a progressive and
      cumulative decrease in cardiac output (CO), heart rate, and dP/dtmax, Regional
      coronary venous oxygen extraction (C(a-cv)O2) transiently increased after 3
      micrograms/kg DEX and decreased 15 min after 10 micrograms/kg DEX. LVEDP
      transiently increased after 3 and 10 micrograms/kg DEX. The changes after DEX 10
      micrograms/kg differed from those after lower doses: MAP (35%), CO (50%), stroke
      volume (33%), C(a-cv)O2 (15%) and myocardial oxygen extraction (33%) were all
      decreased. Myocardial oxygen supply and demand decreased in parallel.
      CONCLUSIONS: 1) The cardiovascular response to IV DEX in goats is similar to man.
      2) In goats after DEX, systemic and coronary vasoconstriction are short-lived,
      and 3) the balance between myocardial oxygen supply and demand is maintained.

PMID- 9265925
TI  - Effects of open heart surgery on oral mucous host defence systems.
AB  - BACKGROUND: The immune response is affected by anaesthesia and surgery. This
      study was carried out on the effects of open heart surgery on the oral mucous
      host defence system, which is part of the common mucosal immune system. METHODS:
      Amylase, nonimmunological (lysozyme, myeloperoxidase, hypothiocyanite and
      thiocyanate) and immunological (IgA, IgG, and IgM) mucous host defence factors as
      well as oral bacterial flora were determined in the saliva of 18 patients
      undergoing open heart surgery preoperatively and on the 2nd, 3rd, and 7th
      postoperative days. To assess the specificity of the changes, the salivary flow
      rate and total protein content were also determined. RESULTS: Stimulated salivary
      flow decreased from 1.8 (1.3-2.2) ml/min (median; 25th and 75th quartiles) to 0.4
      (0.3-0.5) ml/min by the 2nd postoperative day and to 0.4 (0.2-1.0) ml/min by the
      3rd postoperative day (P < 0.001). Amylase, lysozyme, myeloperoxidase, total
      salivary peroxidase and thiocyanate levels increased, whereas hypothiocyanite
      levels decreased postoperatively (p < 0.01-0.001). Their total secretion rate,
      however, was reduced (P < 0.05-0.001) owing to the lowered salivary flow rate.
      IgG and IgM concentrations were raised on the 2nd, 3rd and 7th postoperative days
      (P < 0.05-0.001), and IgA concentrations on the 2nd postoperative day (P < 0.05).
      The total secretion of IgG and IgM as well as their salivary concentrations in
      relation to total protein concentrations also increased. The number of salivary
      anaerobically growing bacteria decreased postoperatively (P < 0.01), but the
      number of salivary streptococci remained unaffected. CONCLUSIONS: Open heart
      surgery decreases the salivary secretion of nonimmunological host defence factors
      and increases the salivary secretion of IgA, IgG and IgM.

PMID- 9265926
TI  - Effects of hypothermia and sternal retractors on median nerve somatosensory
      evoked potentials.
AB  - BACKGROUND: Somatosensory evoked potentials (SEPs) are altered by hypothermia,
      which is often used during cardiopulmonary bypass (CPB). However, the effect of
      hypothermia on SHP amplitudes is unclear. Also, the sternal retractors used
      during open heart surgery are reported to cause brachial plexus distension and
      SEP changes. METHODS: Median nerve SEPs under hypothermic CPB were studied in 29
      elective patients scheduled for open heart surgery. In 23 patients who underwent
      left internal mammary artery (IMA) dissection, the effects of sternal retractors
      on cortical SEP before the initiation of CPB were investigated. RESULTS: A
      latency shift of all SEP components was detected when nasopharyngeal temperature
      decreased from 35.7(SD 0.4) degrees C to 27.8(SD 0.25) degrees C. The mean
      cortical N20 latency was increased by 39% (P < 0.0001), cervical N13 by 33% (P <
      0.0001), and peripheral N9 by 27% (P < 0.0001). The latency changes were
      reversible when normothermia was restored. The effect of hypothermia on SEP
      amplitudes was more complex. The mean amplitude of N20 decreased from 2.7 microV
      to 2.2 microV (P < 0.05) and the amplitude of N13 from 2.5 microV to 2.0 microV
      (P < 0.0001). In contrast, the N9 component showed an increase from 1.4 microV to
      2.1 microV (P < 0.0001) during hypothermia. The sternal retractors did not cause
      significant cortical SEP amplitude changes during IMA dissection or sternotomy.
      Also, the latency changes were small, although significant (P < 0.05).
      CONCLUSION: Despite the moderate amplitude changes produced by hypothermia, SEPs
      can be successfully monitored during hypothermia. Theoretically, the different
      behaviour of amplitude in peripheral and cranial components of SEP during
      hypothermia is interesting. Hypothermia has a more profound effect on synaptic
      transmission, represented by the cortical N20 latency, than on the peripheral
      nerve conduction velocity. Intraoperative monitoring of temperature is essential
      whenever SEPs are recorded. The sternal retractors were not responsible for the
      intraoperative SEP changes.

PMID- 9265927
TI  - Role of zatebradine and propranolol in attenuation of tachycardia produced by
      dobutamine in pigs.
AB  - BACKGROUND: Zatebradine is a new specific bradycardiac agent that selectively
      slows the depolarization in the pacemaker cells of the sinoatrial node. The
      purpose of our investigation was to determine whether the tachycardia induced by
      dobutamine can be attenuated by the administration of zatebradine. The results
      were compared with those produced by propranolol, which is used in the treatment
      of sinus tachycardia. METHODS: Twelve pigs were anesthetized with sodium
      pentobarbital, intubated, and ventilated. After baseline hemodynamic measurements
      were obtained, dobutamine was administered until the heart rate reached 25% above
      baseline. Animals were randomized to one of two groups. Group I received
      zatebradine, 0.5 mg/kg i.v., and Group II received propranolol, 0.5 mg/kg i.v.
      RESULTS: Dobutamine 10 micrograms.kg-1.min-1 increased the heart rate (FIR) by
      25%, and increased mean arterial blood pressure (MAP) left ventricular (LV)
      dp/dt, and cardiac output (CO) (P < 0.05). Zatebradine decreased the HR to
      baseline (P < 0.05) without affecting left ventricular systolic pressure (LVSP),
      left ventricular end diastolic pressure (LVEDP), LV dP/dt, or CO. Stroke volume
      (SV) increased significantly (P < 0.05). Propranolol also reduced HR to baseline,
      but decreased LV dP/dt, LVSP, CO, and SV (P < 0.05). CONCLUSION: Zatebradine
      effectively attenuates the tachycardia caused by dobutamine in anesthetized pigs,
      without reducing cardiac performance.

PMID- 9265928
TI  - The influence of anaesthetic techniques and type of delivery on peripartum serum
      interleukin-6 concentrations.
AB  - BACKGROUND: Interleukin-6 is a pleiotropic cytokine with a wide range of
      physiological activities. It plays an important role in the immuno-neuro-humoral
      axis during stress and surgery. METHODS: Serum interleukin-6 in parturients was
      measured on hospital admission, immediately after birth and 12 and 24 hours
      later. All parturients had uncomplicated pregnancies, and delivered vaginally
      without (n = 31) or with (n = 20) epidural analgesia, or underwent Caesarean
      section under epidural (n = 20) or general (n = 10) anaesthesia. RESULTS: Serum
      interleukin-6 assayed immediately following Caesarean section was low, but peaked
      12 hours later, irrespective of the anaesthetic technique or other foetomaternal
      characteristics. Patients who delivered vaginally showed the highest interleukin
      6 levels immediately after delivery. These were positively correlated with serum
      interleukin-6 on admission and duration of labour. Serum interleukin-6 was
      significantly higher in parturients who had epidural analgesia, and was
      significantly lower in those receiving intravaginal prostaglandins compared to
      those without prostaglandins. CONCLUSION: The interleukin-6 response after
      Caesarean section can be explained by a generalized acute phase response to
      surgery, with no anaesthetic, maternal or neonatal interference. The rapid
      increase in peripartum serum interleukin-6 levels after vaginal delivery
      reflects, in part, cervical ripening or labour, their physiological triggers and
      psychological or physical stress. Regional anaesthesia, duration of labour and
      exogenous prostaglandin administration can modulate the peripartum interleukin-6
      response and subsequently the physiological effects of this cytokine.

PMID- 9265929
TI  - Continuous low-flow tracheal gas insufflation during partial liquid ventilation
      in rabbits.
AB  - BACKGROUND: Both partial liquid ventilation (PLV) and tracheal gas insufflation
      are novel techniques for mechanical ventilation. In this study we examined
      whether PLV superimposed by continuous low-flow tracheal gas insufflation (TGI)
      offers any advantage to the blood gases and lung mechanics in normal-lung rabbits
      compared to the use of PLV only. METHODS: Eighteen anesthetized, paralyzed and
      mechanically ventilated rabbits were used. After obtaining a baseline PaCO2 value
      between 29 and 39 mmHg (3.9 and 5.2 kPa), the animals were assigned to three
      equal groups according to the ventilation they received--A group: PLV
      superimposed by TGI; B group: PLV only; and C group: continuous mandatory
      ventilation (CMV) superimposed by TGI. Serial arterial blood gases, pH and lung
      mechanics were measured. RESULTS: The animals in each group were hemodynamically
      stable. In the case of the A group, PaO2 continuously increased, and PaCO2
      stabilized around 40.8 +/- 5.5 mmHg (5.4 +/- 0.7 kPa, mean +/- SD, NS). In the B
      group, the tendency for PaO2 to increase was not as definite; PaCO2 continuously
      increased from 35.2 +/- 2.3 mmHg (4.7 +/- 0.3 kPa) to 56.3 +/- 12.7 mmHg (7.5 +/-
      1.7 kPa, P < 0.05) at the end of the experiment. In the C group, PaO2 and PaCO2
      were stable during the observation period. The superimposition of TGI on PLV did
      not decrease the airway pressures compared to PLV alone. CONCLUSION: In summary,
      continuous low-flow TGI superimposed on PLV can decrease and stabilize the PaCO2
      elevation caused by the initiation of PLV.

PMID- 9265931
TI  - Caudal clonidine and bupivacaine for combined epidural and general anaesthesia in
      children.
AB  - BACKGROUND: Clonidine produces analgesia by actions on alpha 2-adrenoceptors and
      enhances both sensory and motor blockade from epidural injection of local
      anaesthetics. Low-dose clonidine has been used so far for caudal injection in
      children. Our aim was to study the perioperative effects of high-dose caudal
      clonidine when added to low concentration of bupivacaine for combined epidural
      and general anaesthesia in children. METHODS: After induction of general
      anaesthesia caudal block was performed either with 1 ml.kg-1 bupivacaine 0.175%
      with the addition of clonidine 5 micrograms.kg-1 (n = 20), or with 1 ml.kg-1
      bupivacaine 0.175% (n = 20). The intraoperative anaesthetic requirements, the
      perioperative haemodynamic effects, respiratory rate, sedation score,
      postoperative pain scores and side effects were assessed by a blinded observer. A
      patient-controlled analgesia system was used for postoperative pain relief. The
      quality of postoperative pain relief was assessed using Smiley's pain analogue
      scale. RESULTS: Intraoperative haemodynamic responses did not differ between the
      groups. However, during emergence from general anaesthesia children in the
      clonidine group had significantly lower heart rates and blood pressure compared
      to children in the control group. In addition, heart rates and blood pressures
      were also lower in the clonidine group in the early postoperative period (P <
      0.05). Postoperative analgesia was significantly better in the clonidine group as
      evidenced by the total number of requests (3 vs 12, P < 0.05) and the total
      amount of tramadol (20.5 mg vs 72.8 mg, P < 0.05) administered. The duration of
      the caudal analgesia was significantly longer in the clonidine group (20.9 +/-
      7.4 h vs 14.4 +/- 10.9 h, P < 0.05). CONCLUSION: Our results suggest that caudal
      clonidine 5 micrograms.kg-1 enhances and prolongs caudal blockade with
      bupivacaine (1.175% in children. It also blocks sympathoadrenergic responses
      during emergence from anaesthesia. Sedation and cardiovascular effects are
      observed up to 3 h into the postoperative period.

PMID- 9265930
TI  - Postoperative epidural infusion of morphine and bupivacaine is safe on surgical
      wards. Organisation of the treatment, effects and side-effects in 2000
      consecutive patients.
AB  - BACKGROUND: There was an obvious need to improve the quality and safety of our
      postoperative pain treatment and to introduce an improved routine service on
      surgical wards. METHODS: It was decided to use postoperative epidural infusion of
      morphine 0.04 mg/ml and bupivacaine 2.5 mg/ml (0.25%) 4-8 ml/h as pain relief
      after major surgery. An education programme was run emphasising the benefits,
      side-effects and the importance of regular monitoring of pain intensity, vital
      functions (respiratory rate, blood pressure, heart rate), motor function of the
      legs and the need for additional drugs in order to detect side-effects as well as
      lack of adequate analgesic effect. A detailed observation sheet was used
      collecting information every 2 h throughout the epidural treatment period in
      order to secure monitoring and adjustment of the treatment. Close contact was
      maintained with the wards. RESULTS: We present a detailed analysis of our first
      2000 postoperative patients, mainly after orthopaedic (46.1%), gastrointestinal
      (32.0%), urologic (8.7%) and vascular (8.5%) surgery. Duration of the treatment
      was less than 24 h in 41.4% and more than 48 h in 29.7%. Pain relief was adequate
      in most patients, best after vascular surgery in the lower extremities (mean VAS
      0.15/10.0 (95% confidence interval 0.09-0.23)) and less after gastrointestinal
      (mean VAS 0.49/10 (0.43-0.54)) and thoracic surgery (mean VAS 0.59/10 (0.38
      0.81)). The infusion was stopped due to respiratory depression in 3 patients
      (0.15%). Four (0.2%) had systolic blood pressure < 80 mmHg and had to be treated
      with vasopressors. A total of 56 (2.8%) patients were considered to be problem
      patients due to excessive sedation (0.4%), hypotension (0.7%), respiratory
      depression (1.6%) or lower extremity paralysis (0.05%). All patients had urinary
      catheter until 6 h after termination of the epidural treatment. One patient had
      the epidural catheter accidentally placed subarachnoidally and experienced severe
      respiratory depression. No permanent sequelae were recorded in the postoperative
      patients, but 2 traumatised patients developed epidural abscesses after 3 weeks
      of treatment, which resulted in lower extremity paralysis. Late response to the
      warning signs might have contributed to the irreversible paraplegia. CONCLUSION:
      Our experience with this postoperative epidural analgesia regime is favourable.
      It has been easy to administer and monitor. Pain relief was excellent, side
      effects were few and picked up by the established routines followed by the ward
      staff except in the 2 trauma patients who developed epidural abscesses. The staff
      on the surgical wards were motivated for this kind of work. Education and strict
      surveillance routines are mandatory in order to secure prompt action when warning
      signs develops (e.g. lower limb paralysis).

PMID- 9265932
TI  - Weight gain during pregnancy does not influence the spread of spinal analgesia in
      the term parturient.
AB  - BACKGROUND: It is still controversial whether the spread of spinal anaesthesia in
      pregnancy is influenced by particular physique. Investigation was based on a
      clinical observation that parturients with a pronounced "pregnant" physique, e.g.
      generalised oedema and heavy abdomen, tended to develop more cephalad sensory
      blockades than parturients without these physical signs. Using weight gain during
      pregnancy as a measure for the physique at term, we aimed to determine whether
      this parameter influences the distribution of analgesia after subarachnoidal
      injection of plain bupivacaine. METHODS: Thirty women presenting for elective
      Caesarean section were studied. All the women received 13.5 mg plain bupivacaine
      via subarachnoid injection at the L2-3 interspace. Thirty minutes after the
      injection, while the women were in the supine position with a left lateral tilt
      on a horizontal operating table, the maximum cephalad extent of sensory analgesia
      (loss of sensation to sharpness of pinprick) was determined. RESULTS: Neither
      weight gain during pregnancy (6-22 kg, range), height (152-185 cm), weight (56-98
      kg) nor body-mass index (20.2-31.8 kg/m2) correlated with the cephalad spread of
      sensory blockade. CONCLUSION: In parturients, weight gain during pregnancy,
      height, weight and body-mass index did not influence the extent of sensory
      analgesia after subarachnoidal administration of plain bupivacaine.

PMID- 9265933
TI  - Pharmacodynamic modelling of the analgesic effects of piritramide in
      postoperative patients.
AB  - BACKGROUND: The concentration-effect relationship of piritramide, a synthetic
      opioid analgesic predominantly used for postoperative analgesia and
      analgosedation, has not been reported so far. METHODS: Twenty-four patients of
      both genders aged 58.1 (11.7) yr (mean (SD)) received inhalational anaesthesia
      for abdominal surgery. Postoperative pain was assessed with a visual analogue
      scale (VAS). Analgesia was provided with piritramide, infused at a rate of 7
      micrograms.kg-1.min-1 until analgesia was considered sufficient (VAS < 25) or up
      to a maximum dose of 0.2 mg/kg. The plasma concentrations of piritramide were
      determined by gas chromatography. An inhibitory fractional sigmoid Emax-model was
      used to describe the relation between effect site concentration and perceived
      pain. RESULTS: The equilibration half-life between plasma and effect site
      concentrations (T1/2 (keo)) was 16.8 min (median; range: 4.4-41.6 min). The
      steady-state plasma concentration required to produce 50% of maximum analgesia
      (EC50) was 12.1 ng/ml (range: 2.9-29.8 ng/ml) and correlated with initial pain
      intensity. The slope factor gamma was 1.9 (range: 0.5-6.1) and increased with
      age. Clinically relevant respiratory depression did not occur. Due to the
      relatively large equilibration half-life of the effect compartment, the context
      sensitive half-time of the effect site concentrations after short-time
      administration (< 2 h) clearly exceeded those of alfentanil, sufentanil, and
      fentanyl. CONCLUSIONS: The analgesic effect of piritramide was adequately
      described by an inhibitory fractional Emax-model. In order to overcome the
      pronounced hysteresis, piritramide should initially be administered as an
      intravenous bolus of at least 5 mg.

PMID- 9265934
TI  - Interaction between sufentanil and U-50488H with respect to antinociception and
      respiratory depression in rats.
AB  - BACKGROUND: Opiate receptors have been argued to differentially regulate
      analgesia and respiratory depression. In order to validate possible interactions
      between the opiate mu- and kappa-receptors, interactions between sufentanil and U
      50488H were studied in rats. METHODS: Rats equipped with an arterial catheter
      were tested in the tail flick latency (TFL) test after intravenous treatment with
      sulentanil (a mu-agonist), U-50488H (a kappa-agonist) or fixed ratio combinations
      of both drugs. Simultaneously, respiratory changes were monitored by blood gas
      analysis. RESULTS: The ED50s of sufentanil for a TFL > 6.0 and > or = 10.0 s were
      0.0002 and 0.00059 mg/kg. For U-50488H the corresponding values were 1.53 and
      8.11 mg/kg. Using a fixed dose ratio of 1/10,000, an additivity was demonstrated
      between sufentanil and U-50488H in terms of antinociception. With regard to
      respiratory parameters, PaCO2 significantly increased after all doses of
      sufentanil early after treatment. At the higher doses tested, there was also a
      decrease in PaO2 and O2 saturation. For U-50488H only the highest doses resulted
      in an early and small shift in PaCO2. The combination of sufentanil/U-50488H
      resulted in only a small increase in PaCO2 at the highest dose regimen tested.
      CONCLUSION: The results presented here demonstrate that drug mixtures of
      sufentanil and U-50488H can be additive with respect to antinociception with
      additionally less risk for respiratory side-effects, as compared with sufentanil
      alone. Therefore, a combination of mu- and kappa-opiate-receptor agonists might
      be more beneficial than each agent alone.

PMID- 9265935
TI  - Analgesic and psychomotor effects of thiopental at subanesthetic concentrations
      in human volunteers.
AB  - BACKGROUND: Studies of the effects of barbiturates on the modulation of pain have
      produced mixed results. In a prospective, double-blind, randomized, placebo
      controlled trial, we studied the effects of thiopental at presumed steady-state,
      "conscious sedation" levels on cold-pressor-induced pain in 12 healthy
      volunteers. METHODS: Five drug conditions were used, each condition consisting of
      an injection (either drug or placebo) with a 20-min infusion and a 160-min
      recovery period. The conditions were placebo (saline), thiopental targeted to
      three effect-site concentrations, and fentanyl (1.4 micrograms/kg), as a positive
      control to verify test sensitivity to analgesic drugs. The three thiopental
      concentrations were modeled (STANPUMP) to achieve effect-site concentrations of
      5, 7.5, and 10 micrograms/ml using a bolus and a three-step continuous infusion.
      Five minutes into the infusion period and 115 min after the infusion period was
      terminated, subjects immersed their forearms in ice cold water for 3 min while
      pain and behavioral assessments were recorded. RESULTS: Thiopental at the highest
      dose produced a significant reduction (P < 0.05) in self-reported pain intensity
      both at 5 min into the infusion period and at 115 min after termination of the
      infusion. Fentanyl reduced pain intensity during the first immersion only.
      Thiopental changed subjects' moods and psychomotor performance in a dose-related
      fashion. CONCLUSIONS: Our laboratory results do not support the long-held belief
      that barbiturates are "antanalgesic" or hyperalgesic, at least for cold-pressor
      induced pain.

PMID- 9265936
TI  - Minimum alveolar concentration of sevoflurane for tracheal extubation in
      children.
AB  - BACKGROUND: One advantage of tracheal extubation during deep anaesthesia is that
      respiratory complications are reduced. Sevoflurane is a suitable anaesthetic
      agent for children. This study was conducted to determine the minimum alveolar
      concentration of sevoflurane required to prevent cough or movement during and
      after tracheal extubation (MACextubation). METHODS: We studied 30 nonpremedicated
      children, aged 2-10 yr, undergoing plastic surgery. They were allocated randomly
      to five groups (end-tidal sevoflurane concentrations: 2.0, 2.5, 3.0, 3.5, 4.0%).
      After surgery, 60% nitrous oxide was discontinued and the target concentration of
      sevoflurane was maintained for at least 10 min in 100% oxygen, then the trachea
      was extubated to determine MACextubation. Logistic regression was used to
      estimate MACextubation of sevoflurane. RESULTS: MACextubation was 2.3 (0.2;
      standard error)% (95% confidence limits: 1.2% and 2.7%). CONCLUSIONS: Tracheal
      extubation in 50% of anaesthetized children age 2-10 yr may be accomplished
      without coughing or moving at 2.3% end-tidal concentration of sevoflurane.

PMID- 9265937
TI  - Intravenous dolasetron and ondansetron in prevention of postoperative nausea and
      vomiting: a multicenter, double-blind, placebo-controlled study.
AB  - BACKGROUND: Intravenous dolasetron mesilate has shown efficacy in the prevention
      of postoperative nausea and vomiting (PONV) when administered as a single dose
      prior to emergence from anesthesia. This trial compared intravenous dolasetron
      and ondansetron for the prevention of PONV when administered at induction of
      anesthesia. METHODS: This double-blind, placebo-controlled, multicenter trial
      randomized patients to one of four single IV treatments placebo, 25 or 50 mg
      dolasetron, or 4 mg ondansetron. Efficacy was measured by complete response (0
      emetic episodes and no rescue medication), nausea severity and patient
      satisfaction as measured on a visual analog scale (VAS), investigator's rating,
      of nausea severity, and total response (complete response with no nausea [< or =
      5 mm VAS]). RESULTS: 514 patients at 24 sites were evaluated for efficacy. The 50
      mg dolasetron and 4 mg ondansetron doses were statistically equivalent, and
      superior to placebo, for all efficacy measures. Complete response rates were 49%,
      51%, 71% and 64% for placebo, 25 and 50 mg dolasetron, and ondansetron,
      respectively. Dolasetron 50 mg was statistically superior to 25 mg dolasetron for
      complete response, total response, VAS maximum nausea, time to first emetic
      episode, and patient satisfaction. The majority of adverse events were of mild-to
      moderate intensity. Headache was the most frequently reported treatment-related
      adverse event with a 3%-5% incidence across treatments. CONCLUSION: When given at
      induction of anesthesia, 50 mg intravenous dolasetron is equivalent to 4 mg
      ondansetron and superior to 25 mg dolasetron and placebo for the prevention of
      PONV. All treatments were safely administered and well tolerated.

PMID- 9265938
TI  - Nitrous oxide reduces inspired oxygen fraction but does not compromise
      circulation and oxygenation during hemodilution in pigs.
AB  - BACKGROUND: The use of nitrous oxide (N2O) during hemodilution has been
      questioned. Nitrous oxide reduces the inspired oxygen fraction (F1O2), depresses
      myocardial function and may reduce cardiac output (CO) and systemic oxygen
      delivery (DO2SY). The aim of this study was to evaluate the importance of the
      effects of nitrous oxide on systemic and myocardial circulation and oxygenation
      during extreme, acute, normovolemic hemodilution. METHODS: Ten midazolam-fentanyl
      pancuronium anesthetized pigs were exposed to 65% N2O before and after extreme
      isovolemic hemodilution (hematocrit 33 +/- 1% and 10 +/- 1%, respectively).
      Systemic and myocardial hemodynamics, oxygen delivery and consumption and blood
      lactate were measured before (at F1O2 1.0 and 0.35) and during N2O exposure.
      RESULTS: Hemodilution caused an increase in CO from 137 +/- 43 to 229 +/- 32
      ml.kg-1.min-1 (P < 0.01), a decrease in systemic vascular resistance (from 42 +/-
      14 to 20 +/- 4 mmHg.L-1.min-1, P < 0.05), a decrease in mean arterial blood
      pressure (from 119 +/- 19 to 100 +/- 26 mmHg, P < 0.05) and a decrease in DO2SY
      from 21.1 +/- 6.9 to 13.7 +/- 2.1 ml.kg-1.min-1 (P < 0.01). Cardiac venous blood
      flow increased by 135% (P < 0.01) and cardiac venous saturation from 25 +/- 6 to
      41 +/- 5% (P < 0.05). After hemodilution, changing F1O2 from 1.0 to 0.35 reduced
      arterial blood oxygen content from 59.4 +/- 3.7 to 52.3 +/- 5.1 ml.L-1 (P <
      0.01), mixed venous saturation (SvO2) from 75 +/- 9 to 47 +/- 7% (P < 0.05) and
      DO2SY from 13.7 +/- 2.1 to 11.9 +/- 2.3 ml.kg-1.min-1 (P < 0.05). Dissolved
      oxygen at F1O2 = 1.0 and F1O2 = 0.35 constituted 25.4 +/- 3.1% and 10.1 +/- 1.5%,
      respectively, of systemic oxygen delivery after hemodilution, compared with 10.7
      +/- 1.2% and 3.9 +/- 0.5% before hemodilution (P < 0.01). Left ventricular oxygen
      delivery and consumption were unchanged. Exposure to N2O did not affect mean
      arterial blood pressure or systemic vascular resistance before or after
      hemodilution. After hemodilution during N2O-exposure, CO and DO2SY decreased by
      9% (P < 0.01 and P < 0.05, respectively), but no changes in SvO2, systemic oxygen
      uptake or arterial lactate were observed. The effect of N2O on myocardial
      oxygenation was similar before and after hemodilution; cardiac venous blood flow,
      left ventricular oxygen delivery and uptake decreased, but no animals showed left
      ventricular lactate production. CONCLUSION: Nitrous oxide did not compromise
      systemic and myocardial circulation and oxygenation during acute normovolemic
      hemodilution in pigs. Possible adverse effects from the use of nitrous oxide
      during hemodilution seem to be related to a reduced F1O2, reducing the safety
      margin for systemic oxygen delivery.

PMID- 9265939
TI  - Effects of halothane and isoflurane on left ventricular diastolic function during
      surgical stress in patients with coronary artery disease.
AB  - BACKGROUND: The effects of inhalation anesthetics on left ventricular (LV)
      systolic function are well documented, while the effects of these agents on LV
      diastolic function have mainly been evaluated in animal studies, with conflicting
      results. METHODS: We investigated the effects of halothane and isoflurane, when
      used to control the stress response to sternotomy in 33 patients with coronary
      artery disease (CAD). LV early diastolic relaxation and end-diastolic stiffness
      were evaluated from mitral Doppler flow profiles, transesophageal two-dimensional
      echocardiography, and central hemodynamic measurements. Measurements were
      performed a) after induction of anesthesia, b) after volume loading, c) prior to
      surgery and d) during surgery, 10 min after introduction of the inhalation
      anesthetic. The effects of the anesthetics on Doppler indices reflecting early
      diastolic relaxation, and on the left ventricular end-diastolic pressure-area
      (LVED P/A) relationship, were studied. RESULTS: When data obtained during
      surgical stress were compared to the control situation, we found an increase in
      the LV filling pressures in both groups, while only the isoflurane group showed
      an increase in heart rate. An increase in end-systolic LV area and decreased
      fractional area change was present in the halothane group, while an increase in
      LV end-diastolic area, and similar changes in the mitral Doppler indices
      (decreases of deceleration rate and time of early diastolic filling), indicating
      an impairment of early diastolic relaxation, was present in both groups.
      Isoflurane induced a displacement of the LVED P/A relationship leftwards from the
      baseline LVED P/A curve. CONCLUSION: Both halothane and isoflurane impair early
      diastolic relaxation in patients with CAD, when used to control intraoperative
      surgical stress. In contrast to halothane, isoflurane induced a change in the
      LVED P/A relationship, suggestive of an increased LVED stiffness.

PMID- 9265940
TI  - alpha 1-adrenoceptor stimulation is able to reverse halothane-induced cardiac
      depression in isolated rat hearts.
AB  - BACKGROUND: Stimulation of myocardial alpha 1-adrenoceptors has been shown to
      exert positive inotropic effects through a cyclic AMP-independent mechanism. The
      purpose of this study was to examine if alpha 1-adrenoceptor stimulation is able
      to attenuate myocardial depression produced by exposure to halothane, and to test
      if alpha 1-adrenoceptor stimulation alters myocardial oxygen supply-demand
      balance in hearts exposed to halothane. METHODS: The effects of phenylephrine
      were examined in 7 isolated perfused rat hearts. Variables measured were: heart
      rate, isovolumetric peak left ventricular pressure (LVP), LV dP/dt, coronary
      arterial flow, myocardial O2 delivery (DO2), myocardial O2 consumption (MVO2) and
      the ratio of DO2/MVO2. Each heart was exposed to phenylephrine cumulatively 0.1
      microM, 0.3 microM, 1 microM and 3 microM under the administration of 1%
      halothane in the presence of propranolol 1 microM. RESULTS: Halothane 1%
      decreased the heart rate by 9 +/- 3%, LVP by 37 +/- 3%, and LV dP/dt by 35 +/-
      2%. Phenylephrine restored these decreases to the baseline levels. Phenylephrine
      maintained or further enhanced the reductions in coronary flow and DO2 produced
      by halothane, resulting in a decrease in the DO2/ MVO2 ratio. CONCLUSION: alpha 1
      adrenoceptor stimulation is capable of restoring direct cardiac depressant
      effects of halothane with a possible impairment of the oxygen supply-demand
      balance.

PMID- 9265941
TI  - Intermittent airway obstruction in a child caused by a cervical lipoblastoma.
AB  - Severe intermittent airway obstruction was caused by a lipoblastoma in a 9-month
      old boy. The tumor was located in the lower part of the neck and moved into the
      thoracic inlet causing compression of the trachea when he moved his head
      forwards. A tumor compressing or obstructing the trachea is infrequently the
      cause of airway obstruction in infants and children. Nevertheless, overlooking a
      tumor may have serious consequences when giving anesthesia due to the risk of
      difficulties with artificial ventilation depending on the localisation of the
      tumor. Every case of unexplained respiratory failure must be subject to a
      systematic approach that considers lung disease, bronchoconstriction, large
      airway obstruction, and external compression of the airway.

PMID- 9265942
TI  - Bacterial airway filters in combination with inhalation therapy in the ICU.

PMID- 9265943
TI  - Morbidity and mortality associated with anaesthesia.

PMID- 9265944
TI  - Is the need for analgesia influenced by the time of day?

PMID- 9265945
TI  - Use of the mirror of indirect laryngoscopy for detection of esophageal
      intubation.

PMID- 9265946
TI  - Designing a new generation of antidepressant drugs.
AB  - Although longer-term adaptive changes in receptor sensitivity may better explain
      the delayed onset of action of antidepressants, the mechanism based on acutely
      elevated noradrenaline (NA) and serotonin (5-HT) synaptic levels remains the
      basis for new drug design. The dual action concept, which postulates that effects
      on both NA and 5-HT are more advantageous than a selective action on serotonin
      reuptake (SSRI), has been used to design new antidepressants such as venlafaxine
      and mirtazapine. Both drugs enhance NA and 5-HT neurotransmission with little
      affinity for receptors mediating tricyclic-like side effects. Mirtazapine, the
      prototype noradrenergic and specific serotonergic antidepressant (NaSSA),
      specifically enhances 5-HT1 neurotransmission and blocks 5-HT2 and 5-HT3
      receptors, and in contrast to venlafaxine lacks SSRI-like and adverse
      cardiovascular side effects. The unique pharmacological action of mirtazapine is
      a result of implementation of two concepts: dual action as a basis of efficacy
      combined with receptor-specific action as a basis of tolerability.

PMID- 9265947
TI  - Pharmacogenetics of antidepressants: clinical aspects.
AB  - Plasma concentrations and response to antidepressants vary considerably between
      patients treated with similar dosages. Most antidepressants and also
      antipsychotics are metabolized by the polymorphic debrisoquine/sparteine
      hydroxylase, i.e., cytochrome P450 (CYP)2D6. About 7% of Caucasians are poor
      metabolizers (PM), and such patients might develop adverse drug reactions when
      treated with recommended doses of, for example, tricyclic antidepressants. In
      contrast, ultrarapid metabolizers with multiple CYP2D6 genes might require high
      doses of such drugs for optimal therapy. The mean CYP2D6 activity is lower in
      Oriental than in Caucasian populations, because of a frequent mutation causing
      decreased enzyme activity. Drugs metabolized by the same enzyme may interact with
      each other. For example, the potent CYP2D6 inhibitor fluoxetine increases the
      plasma concentrations of tricyclic antidepressants. Another enzyme catalyzing the
      metabolism of antidepressants is the polymorphic S-mephenytoin hydroxylase.
      CYP2C19, which catalyses the metabolism of, for example, citalopram, clomipramine
      and moclobemide. Various probe drugs may be used for phenotyping CYP2D6
      (debrisoquine, dextromethorphan and sparteine) and CYP2C19 (mephenytoin and
      omeprazole). Allele-specific polymerase chain reaction (PCR)-based methods are
      now available for genotyping using leukocyte DNA. A major advantage of genotyping
      compared with phenotyping is that the former may be performed in blood samples
      from patients irrespective of treatment.

PMID- 9265948
TI  - Meta-analysis of randomized, double-blind, placebo-controlled, efficacy and
      safety studies of mirtazapine versus amitriptyline in major depression.
AB  - A meta-analysis was performed on efficacy and safety data from 4 randomized,
      double-blind, 6-week, single-center studies comparing mirtazapine (n = 194; 5-35
      mg/day) with amitriptyline (n = 193, 40-280 mg/day) and placebo (n = 193) in
      outpatients with a DSM-III diagnosis of major depressive episode. On all the main
      efficacy variables both active drugs consistently produced significantly greater
      improvements and significantly greater percentages of responders or remitters
      than placebo. The meta-analysis of adverse events shows that mirtazapine was
      better tolerated than amitriptyline, particularly with respect to anticholinergic
      and cardiac adverse events. There were no differences between mirtazapine and
      placebo regarding the incidence of serotonergic adverse events. In conclusion,
      the results of this meta-analysis demonstrate that mirtazapine is as effective as
      amitriptyline but has a better tolerability profile.

PMID- 9265949
TI  - Mirtazapine: pharmacology in relation to adverse effects.
AB  - Mirtazapine is a new antidepressant that falls into the general class of receptor
      blocking drugs rather than being an uptake or enzyme inhibitor. It can be
      described as a noradrenergic and specific serotonergic antidepressant (NaSSA).
      The unique pharmacology of mirtazapine means that it has a very different side
      effect profile from the tricyclic antidepressants, producing less alpha 1
      adrenergic and muscarinic blockade, and the selective serotonin reuptake
      inhibitors (SSRIs) and the serotonin-noradrenaline reuptake inhibitors (SNRIs),
      causing much less nausea and sexual dysfunction by virtue of its blockade of 5
      HT2 and 5-HT3 receptors.

PMID- 9265950
TI  - Molecular pathogenesis of astrocytoma and glioblastoma multiforme.
AB  - Our understanding of the complexity of genetic abnormalities involved in the
      tumourigenesis of malignant gliomas is as yet rudimentary. However, we can
      discern distinctive patterns of loss of genetic material and amplification of
      chromosomal regions that characterize both the different types of gliomas as well
      as the different malignancy grades. In this review, we discuss through specific
      examples of recent work on astrocytomas and glioblastoma multiforme, the
      importance of several tumour suppressor genes and oncogenes in the development of
      these glial tumours. In conclusion it would seem that distinct genetic changes in
      different genes, the protein products of which interact in particular growth
      control mechanism may lead to the same cellular abnormality. It seems likely that
      many further genetic abnormalities affecting genes coding for proteins, either
      involved in the cellular mechanisms yet identified or in new growth control
      mechanisms. Will be found in the near future.

PMID- 9265951
TI  - Prognostic factors in oligodendrogliomas.
AB  - An outcome analysis was performed on 96 patients with pure cerebral
      oligodendrogliomas operated in the 30-year period 1962 to 1991. The most
      important predictive prognostic factors were youth and no neurological deficit,
      demonstrated as a median survival for the group younger than 20 years of 17.5
      years and for the group older than 60 years of 13 months. The group without
      neurological deficits had a 5-years survival of 43 per cent while the group with
      deficits had a 5-years survival of 5 per cent. The 5-years survival for
      oligodendroglioma of grade II was 46 per cent and for grade III 10 per cent. We
      found no effect of radiotherapy on survival, neither in the whole material or in
      any subgroup.

PMID- 9265952
TI  - Pharmacokinetics of Na2B12H11SH (BSH) in patients with malignant brain tumours as
      prerequisite for a phase I clinical trial of boron neutron capture.
AB  - The disposition of Na2B12H11SH (BSH) in patients with malignant glioma has been
      investigated, in preparation for a Phase I clinical trial of boron neutron
      capture therapy. BSH was found to possess a linear disposition over the dosage
      interval investigated (up to 75 mg/kg). A bi-phasic blood pharmacokinetics was
      observed. Tumour-to-blood ratios showed variations between patients between 0.08
      and 5.1. The data allow the definition of amount of BSH and timing of infusion
      for a Phase I clinical trial protocol.

PMID- 9265953
TI  - Proliferative potential in pituitary adenomas: measurement by monoclonal antibody
      MIB-1.
AB  - The proliferative potential of 45 pituitary adenomas was compared with their
      biological behaviour as determined by immunohistochemical studies, radiological
      findings, and clinical manifestations. The PCI (proliferating cell index) as
      measured using antibody MIB-1 in this study ranged from 0.05 to 4.80%, with an
      average PCI of 1.49 +/- 0.19% (mean +/- standard error of the mean). There was no
      significant correlation between proliferation and hormonal state, maximum size,
      intra-adenomatous haemorrhage, or invasiveness. However, a PCI > or = 1.5%
      appeared to correlate with the likelihood of tumour regrowth (regrowth rate:
      50%); for PCIs < 1.5%, the rate was 16%. Regrowth adenomas had a higher mean MIB
      1 PCI than non-regrowth adenomas [2.34 +/- 0.58% (SE) versus 1.14 +/- 0.16%, p <
      or = 0.05]. MIB-1 PCIs may provide information that is useful for planning follow
      up studies and treatment after surgical resection.

PMID- 9265954
TI  - Different release of cytokines into the cerebrospinal fluid following surgery for
      intra- and extra-axial brain tumours.
AB  - To elucidate the role of cytokines in brain repair processes and in local
      inflammation after neurosurgical procedures, cerebrospinal fluid (CSF) samples
      from 8 patients with intra-axial tumours and 8 patients with extra-axial tumours
      were analysed for interleukin (IL)-1 beta, IL-1 receptor antagonist (IL-1 ra), IL
      6, IL-8, IL-10, and tumour necrosis factor (TNF)-alpha at the beginning and after
      surgery. Levels of IL-6 and IL-8 increased dramatically in all patients just
      hours after surgery and fell during subsequent days. IL-1 beta was found only in
      low amounts in the CSF of both patient groups. Other cytokines demonstrated
      different courses. In patients with intra-axial tumours IL-1 ra peaked two to
      four hours after surgery with a subsequent decrease. In patients with extra-axial
      tumours there was a continuous low-level IL-1 ra release into the CSF without a
      peak. TNF-alpha was not present in detectable levels in the CSF after surgery for
      extra-axial tumours but was found to peak two to four hours after surgery for
      intra-axial tumours. IL-10 was detected in the CSF of both patient groups, but a
      higher peak was seen after surgery for extra-axial tumours. These results suggest
      different requirements for the cytokine response and an involvement of different
      cell types in cytokine release. However, the analysis of the CSF from both
      patient groups showed no differences in cell counts and populations, with a mild
      pleocytosis being present in both patient groups after surgery. Therefore, we
      conclude that after surgery for extra-axial tumours cytokines were predominately
      produced by non-immune cells stimulated through hypoxia or mechanical irritation.
      After surgery for intra-axial tumours with a significant brain injury immune
      cells-activated by necrotic material-seen to be involved in the process of
      cytokine synthesis. In these cases an additional IL-1ra and TNF-alpha peak was
      found and these cytokines may be markers for cerebral injury.

PMID- 9265955
TI  - Stereotactic angiographic localization as an adjunct to surgery of cerebral
      mycotic aneurysms: case report and review of the literature.
AB  - Less than 10% of all aneurysms affecting the arterial cerebral circulation are
      mycotic in nature. They occur in the setting of bacterial endocarditis and are
      the cause of considerable morbidity and mortality of affected patients. In
      selected cases surgery may play a curative role in the treatment plan. These
      aneurysms frequently arise in distal arterial branches, and their localization
      during surgery may at times prove laborious. We report the case of a mycotic
      aneurysm of a distal branch of the anterior cerebral artery surgically treated
      with the help of angiographic stereotactic localization. Stereotaxy should thus
      be regarded as a pertinent adjunct in selected cases of surgical treatment of
      distal mycotic cerebral aneurysms.

PMID- 9265956
TI  - Spondylodesis in the treatment of segmental instability of the lumbar spine with
      special reference to clinically verified instability.
AB  - We analysed the outcome of 42 consecutive patients suffering from low back pain
      and segmental instability of the lumbar spine who underwent spondylodesis with
      transpedicular fixation. There were 29 (69%) females and 13 (31%) males with a
      mean age of 47 +/- 9 years (range 23 to 66 years). The presence of clinically
      verified instability was a basic requirement for operative treatment, with at
      least one clinical sign of instability positive in all patients. Radiological
      signs of instability were detected in only 74% of the patients. After a
      postoperative follow-up of one year, lumbar fusion was found in 38 (90%)
      patients. The fusion was classified as complete in 18 (43%) and as partial in 20
      (47%) patients. No fusion there was detected in 4 (10%) patients. Low back pain
      was completely abolished in 19 (45%) and markedly diminished in 15 (36%) patients
      in (17%) patients, low back pain had remained unchanged and become worse in 1
      (2%) patient. Clinical signs and symptoms of instability were still detected in
      10 (24%) patients. As compared to the pre-operative situation, the decrease in
      clinical instability was statistically significant (p = 0.02). Moreover, a
      significant correlation was observed between the persistence of clinically
      verified instability and a poor postoperative outcome in daily activities. Of all
      patients, 17 (40%) returned to work during the period of follow up. Based on the
      good outcome of our patients, the results of this study show that clinical signs
      and symptoms of instability can be successfully used as selection criteria for
      lumbar spondylodesis.

PMID- 9265957
TI  - Quantitative cerebral blood flow and metabolism determination in the first 48
      hours after severe head injury with a new dynamic SPECT device.
AB  - OBJECTIVE: To determine cerebral blood flow (CBF) and metabolism in the acute
      phase after severe head injury by a new dynamic SPECT device using 133Xenon and
      to evaluate a possible role of CBF and metabolism in the determination of
      prognosis. DESIGN: Prospective study. SETTING: General intensive care unit in a
      universitary teaching hospital. SUBJECTS: 23 severely head injured patients
      having CT scan and CBF determination, intracranial pressure (ICP) and jugular
      bulb oxygen saturation monitoring in the first 48 hours. MEASUREMENTS AND MAIN
      RESULTS: CBF varied from 18.0 to 60.0 ml/100 g/min. No correlation was found
      between early CBF and severity of trauma evaluated with the Glasgow Coma Score
      (GCS) (F = 2.151, p = 0.142) and between CBF and prognosis at 6 months evaluated
      with Glasgow outcome score (GOS) (F = 0.491, p = 0.622: rs = 0.251, p = 0.246).
      CMRO2 was depressed in relation to the severity of injury, specifically ranging
      from 0.9 +/- 0.5 ml/100 g/min in patients with GCS 3 to 1.7 +/- 0.8 ml/100 g/min
      in patients with GCS 6-7. In no patient with CMRO2 less than 0.8 ml/100 g/min was
      a good outcome observed. A significant correlation was found between GCS and GOS
      (rs = 0.699, p = 0.0002), between CMRO2 and GOS (F = 4.303, p = 0.031; rs =
      0.525, p = 0.013) and between AJDO2 and GOS (F = 3.602, p = 0.046; rs = 0.491, p
      = 0.017). Fronto-occipital ratio (F/O) of CBF distribution was significantly
      lower than normal values (chi 2 = 18.658, p = 0.001) but did not correlate either
      with prognosis (chi 2 = 1.626, p = 0.443) or with severity (chi 2 = 1.913, p =
      0.384). CONCLUSIONS: CBF in the first 48 hours after trauma varies within a large
      range of values and is not correlated with severity and prognosis. Clinical
      evaluation with GCS and CMRO2 are much more reliable indicators of severity of
      head trauma and have a significant role in the determination of prognosis. F/O
      ration is significantly altered from normal values confirming "post-traumatic
      hypofrontalism" but does not correlate with severity and prognosis.

PMID- 9265958
TI  - Dipole modelling and intracranial EEG recording: correlation between dipole and
      ictal onset zone.
AB  - This study includes 11 patients (3 males, 8 females) with mean age of 29 years
      (range: 15-42 years) who underwent a presurgical evaluation for refractory
      complex partial seizures (CPS). In all patients, neuroimaging (1.5 T optimum-MR)
      demonstrated intracranial structural abnormalities (space-occupying: n = 2;
      atrophic: n = 8; dysplastic: n = 1) and video-EEG monitoring showed CPS, because
      of discrepancies in the non-invasive examinations, all underwent additional
      intracranial EEG monitoring. After tailored resective procedures, all but one
      patient became seizure free. Mean follow-up was 30 months (range: 12-52 months).
      Results of intracranial EEG recording were compared with spatiotemporal dipole
      mapping of interictal and ictal epileptic discharges. Interictal dipole modelling
      revealed two distinct dipole patterns. Patients with lesions located in the
      medial temporal lobe uniformly presented a combined dipole that consisted of a
      radial and a tangential component with a high degree of elevation relative to the
      axial plane. Patients with extrahippocampal lesions had a less stable dipole with
      a predominant radial component. Dipole modelling of early ictal discharges
      revealed a striking correspondence with the interictal findings in individual
      patients. Elevation of ictal dipoles was always congruent with localisation based
      on intracranial EEG recordings. Interictal and ictal dipole mapping of medial
      temporal lobe sources may limit the number of surgical candidates for refractory
      CPS that need intracranial EEG recording. Whether ictal dipole modelling can be
      equally useful in extratemporal epilepsy remains to be proven.

PMID- 9265960
TI  - The effect of intraventricular albumin in experimental brain oedema.
AB  - Therapy for vasogenic brain oedema (VBE) is still an unsolved problem.
      Experimental work with the aim of establishing an oncotherapeutic option is
      presented. VBE is performed by focal freeze injury in rats. Using a stereotactic
      head holder hypo- or hyperosmolar human serum albumin is administered via the
      intraventricular route. The goal is to enhance the migration of oedema fluid with
      the aid of oncotic pressures. Early and late results are obtained for each group
      respectively four and twenty-four hours after the infliction of cold injury. The
      efficacy of therapy is evaluated by cerebrospinal fluid (CSF) osmolality,
      cerebral water content, tissue specific gravity, and blood-brain barrier (BBB)
      permeability. Posttherapeutic values for CSF osmolality are obtained by cisterna
      magna puncture. Hyperosmolar CSF after performance of cold injury (p < 0.05) is
      thought to be a result of fluid accumulation in the traumatized region partially
      from the intraventricular space. Posttherapeutic values after hyperosmolar
      albumin administration have revealed iso-osmolar CSF, increase in specific
      gravity (p < 0.001), and decrease in BBB permeability (p < 0.05). These results
      are in accordance with withdrawal of oedema fluid into the ventricles which can
      be interpreted as a positive therapeutic effect. Late results in hyperosmolar
      group have disclosed a hypo-iso-osmolar CSF, persistent increase in specific
      gravity, and no regression. These values have shown that hyperosmolar albumin
      administration does not interfere with CSF circulation. Early results of
      hypoosmolar albumin application are discouraging. This preliminary work of a
      therapeutic trial on VBE may be a basis for future investigations with different
      dosages and time modalities.

PMID- 9265959
TI  - Use of frozen cranial vault bone allografts in the repair of extensive cranial
      bone defects.
AB  - In cranioplasty complexity is proportional to the size of the detect,
      particularly if greater than 50 cm2. If the patient's own bone flap is not
      available, allogenic frozen bone graft can be used instead. Between June 1990 and
      June 1995 twenty cranioplasties with allogenic frozen bone grafts were performed.
      Age of patients ranged between 23 and 63 years (average 38.4 years). Male/female
      ratio was 2:1.7. Size of craniectomy ranged between 65 and 150 cm2 (average 83.3
      cm2). Follow-up ranged between 10 and 58 months (average 41 months). Donors were
      tested to rule out transmissible diseases, infections, sepsis and/or cancer. Bone
      grafts were removed under aseptic conditions, microbiological cultures were
      taken, wrapped in a gauze soaked with Gentamicin sulphate and Bacitracin, sealed
      in three sterilised vinyl plastic bags, and stored in a deep freezer for a
      minimum of 30 days (range 36-93 days, average 67 days), at a temperature of -80
      degrees C. Grafts were placed in the defect after a step was carved on its
      borders to facilitate the contact between host and graft. Vancomycin 1 g. IV/12
      hours and Ceftriaxone 1 g. IV/12 hours were administered for five days. Grafts
      were covered by means of scalp flaps. Only one required a musculocutaneous free
      flap. None was exposed, extruded or had to be removed. Plain skull X-ray studies
      showed progressive remodelling of the grafts. Partial resorption was observed in
      two (2/20, 10%) and loss of thickness in another 3/20 (15%), but with no changes
      in the contour. Biopsies were taken in 3/20 (15%) cases at a second surgical
      procedure. Areas of osteoclastic resorptive activity mixed with others of
      osteoblastic bone apposition, showed replacement with new bone. We conclude that
      cranial vault frozen allografts are a good alternative to autologous bone when
      the latter is absent or not present in sufficient amount.

PMID- 9265961
TI  - Microvascular changes associated with postischaemic hypoperfusion in rats.
AB  - The present study was undertaken to explore the cause of postischaemic
      hypoperfusion through morphological observations of the microstructure of brain
      cortex capillaries in rats with postischaemic hypoperfusion. Sixteen rats were
      used. The left middle cerebral artery of each animal was occluded for one hour (n
      = 8) or 2 hours (n = 8) and was followed by reperfusion for 2 hours. The regional
      cerebral blood flow (rCBF) of the ischaemia induced brain cortex was monitored
      continuously during the experiment and the microstructure of the brain cortex
      capillaries was then observed under electron microscope. Postischaemic
      hypoperfusion was observed in both ischaemia groups. The rCBF after (1.5 hours of
      reperfusion was significantly lower in the 2-hour ischaemia group than in the one
      hour ischaemia group. The number of endothelial microvilli (MV) per capillary in
      the one-hour ischaemia group did not differ significantly from the control (the
      right cortex capillaries), whereas it was significantly higher in the 2-hour
      ischaemia group (p < 0.05). The ratio of the inner diameter to the outer diameter
      of capillaries decreased significantly in both ischaemia groups, and the ratio in
      the 2-hour ischaemia group was significantly lower than that in the one-hour
      ischaemia group (p < 0.05). Thus the present study statistically revealed that as
      postischaemic perfusion of the brains decreases, the number of MV increases, and
      endothelial cells swell more markedly. These microvascular changes seem to
      represent morphological factors associated with postischaemic hypoperfusion.

PMID- 9265962
TI  - Transient cerebral ischaemia in Mongolian gerbils pre-exposed to hypoxia.
AB  - The objective of this study was to clarify whether pre-exposure to hypoxia
      influences neuronal death following transient cerebral ischaemia. Twenty gerbils
      were exposed to 10% oxygen in a chamber for 3 weeks. The other control gerbils (n
      = 20) were fed in normoxia for 3 weeks. Both carotid arteries in the neck were
      occluded with aneurysm clips for 5 minutes under halothane anaesthesia in 30
      gerbils, recirculated and then fed in normoxia. Five animals in both groups were
      sacrificed before, and 2, 4, and 7 days after surgery. The animals were fixed
      with 4% paraformaldehyde and histological study was performed.
      Immunohistochemical study was also done with antibodies against basic fibroblast
      growth factor (bFGF) and vascular endothelial growth factor (VEGF). The neuronal
      death in the hippocampus was more severe in the hypoxic group. Expression of both
      bFGF and VEGF was obvious in the cingulate cortex, corpus callosum and internal
      capsule before clipping in the hypoxic group, but not observed in the normoxic
      group before clipping. We observed the expression of both bFGF and VEGF widely in
      the brain at 2 and 4 days after recirculation in both groups. The expression in
      the hypoxic group was much more prominent than that in the normoxic group. These
      expressions were not observed at 7 days in both groups. Pre-exposure to hypoxia
      followed by transient cerebral ischaemia accelerated neuronal death in the
      hippocampus, and induced the more obvious expression of both VEGF and bFGF
      compared with those in the normoxic group.

PMID- 9265963
TI  - Osteosarcoma of the meninges in association with glioblastoma.
AB  - Primary intracranial osteosarcoma not originating in the skull is a distinctly
      rare tumour, as is post-irradiation sarcoma of short latency. The authors report
      the case of a 56 year old caucasian male who underwent resection of a
      glioblastoma of the left temporal region and was subsequently administered
      partial field external beam radiation therapy (XRT) to a total dose of 5940 cGy.
      Seven months following the completion of XRT, an enhancing region adjacent to the
      surgical site was noted on followup magnetic resonance images (MRI), one which
      increased in size on serial studies. Initial biopsy of the dural lesion adjacent
      to the temporal resection site revealed a sarcoma with a suggestion of osseous
      differentiation. Subsequent reoperation with resection of the lesion showed it to
      be a primary meningeal tumour, and histological evaluation of the lesion
      demonstrated an osteosarcoma. Immunohistochemical staining for p53 protein
      performed on both the original glioblastoma and the subsequently resected
      osteosarcoma showed widespread nuclear positivity. The clinical, radiographic and
      pathologic features of this unusual case are discussed. Meningeal osteosarcoma
      should be included among the rare secondary sarcomas of the meninges which may be
      associated with malignant glioma.

PMID- 9265964
TI  - Dural chondroma with fat tissue.

PMID- 9265965
TI  - Unusual complication of arachnoid cyst: spontaneous rupture into the subdural
      space.

PMID- 9265966
TI  - Mechanisms of antibacterial resistance.

PMID- 9265967
TI  - Bacterial adhesins: determinants of microbial colonization and pathogenicity.
AB  - Bacterial adhesins are a critical determinant of microbial colonization and are
      fundamental to disease pathogenesis. In this chapter, I have reviewed certain
      paradigms that exist with respect to structure, variation of expression, and
      biologic activity. No two adhesins are identical, reflecting the fact that each
      organism has a distinct ecological niche and is exposed to a different set of
      evolutionary pressures. Continued investigation is likely to identify additional
      paradigms and novel nuances. The hope is that we might use all this information
      to improve our approach to the treatment and prevention of bacterial disease.

PMID- 9265968
TI  - New perspectives in type 2 Gaucher disease.

PMID- 9265969
TI  - Carbohydrate-deficient glycoprotein syndrome.
AB  - Carbohydrate-deficient glycoprotein syndrome consists of a group of disorders
      with multisystemic involvement and prominent neurologic symptoms. The full
      clinical spectrum continues to evolve, with four types currently recognized; type
      I is by far the most common. The clinical presentation of CDGS appears more
      severe in infants than in adults. Diagnosis is based on the clinical findings of
      characteristic fat distribution, neurologic impairment, and developmental delay,
      combined with the biochemical finding of cathodally migrating serum
      glycoproteins, transferrin in particular, on isoelectric focusing. Scientific
      evidence supports the hypothesis that abnormal synthesis of N-linked
      oligosaccharides is the basic metabolic defect in CDGS. The complex, multistep
      nature of the N-linked oligosaccharide pathway and the clinical heterogeneity of
      CDGS suggest that several different defects in the pathway can result in this
      disorder. Two specific enzyme defects have been reported: phosphomannomutase
      deficiency in some type I patients and N-acetylglucosamine transferase II
      deficiency in type II patients. Investigations continue into other metabolic
      bases of CDGS. The discovery of some of the enzyme defects paves the way for
      cloning, mutational analysis, and eventually prenatal diagnosis in appropriate
      families. No known treatment exists for CDGS; pallintive care and support is the
      most that can be offered. Family support systems are blossoming both in the
      United States and abroad, giving families the ability to communicate with each
      other and with workers in the field. As more cases are diagnosed and scientific
      research continues, advances in clinical definition, supportive care, nutrition,
      and prenatal diagnosis of CDGS are inevitable.

PMID- 9265970
TI  - Viral myocarditis: diagnosis and management.

PMID- 9265971
TI  - Bilirubin metabolism and kernicterus.
AB  - Neonatal jaundice continues to be a common problem. Kernicterus, although rare,
      continues to be a very real concern in both full-term and preterm infants. The
      diagnosis of kernicterus requires not only bilirubin staining in a characteristic
      pattern in the brain but also neuronal damage. With careful pathologic
      evaluation, kernicterus should be distinguishable from the brain damage
      associated with asphyxia and hypoxia. Early hospital discharge is a risk factor
      for the development of kernicterus. Combining the use of traditional phototherapy
      from above and a fiberoptic blanket from below has improved the effectiveness of
      phototherapy. Clinical trials with SnMP as an inhibitor of heme oxygenase appear
      encouraging; no adverse effects were noted, except for mild, occasional
      photosensitization manifest by erythema in babies receiving phototherapy. One
      theoretical toxicity of inhibitors of heme oxygenase involves the recent
      observation that carbon monoxide (CO) is a neurotransmitter in certain regions of
      the brain, possibly comparable to nitric oxide (NO), and the consequences of such
      inhibition are unknown. More research is needed to improve our understanding
      about the entry of bilirubin into the brain, the predilection of bilirubin for
      certain brain regions, and the cytotoxicity of bilirubin. In the United States,
      there is currently no generally accepted method to predict hyperbilirubinemia or
      kernicterus. Brain stem auditory evoked responses and MRI can both be used
      effectively to monitor the effects of severe hyperbilirubinemia.

PMID- 9265972
TI  - Folic acid: new dimensions of an old friendship.

PMID- 9265973
TI  - Choline: essential for brain development and function.
AB  - Pregnancy and lactation are periods when maternal reserves of choline are
      depleted. At the same time, the availability of choline for normal development of
      brain is critical. Variations in choline intake by mothers influence memory
      performance in their offspring. The mechanisms for this potent effect of choline
      are not yet elucidated but may involve changes in acetylcholine synthesis,
      transmembrane signal transduction, or regulation of apoptosis. These observations
      are important for the obstetrician and pediatrician as they consider the ideal
      dietary intake for mothers and their children.

PMID- 9265974
TI  - The ketogenic diet: 1997.
AB  - There has been a dramatic resurgence of interest in the ketogenic diet during the
      past several years. For many children with difficult-to-control epilepsy, the
      diet presents an alternative approach to trying multiple medications. The
      ketogenic diet's current success rate, when properly executed, greatly exceeds
      that of the medications which have recently become available. Its side effects,
      both cognitive and allergic, appear fewer than most available medications. The
      ketogenic diet is also cheaper than most new anticonvulsants. Even though we now
      know that the diet works, we still do not know how it works. Nor do we know how
      most anticonvulsants work. The mechanism of action of the ketogenic diet appears
      to rely on a fundamental change in the brain's metabolism from that of a glucose
      based energy substrate to a ketone-based substrate. This change is, in some
      fashion, critical to the maintenance of seizure threshold. Why should the source
      of the energy make a difference in seizure threshold? The change in seizure
      threshold appears to occur without affecting the brain's ability to carry out its
      normal complex functions. Could the brain's utilization of an energy substrate
      for seizure control be different from its utilization of energy for normal brain
      function? If so it should it be possible to study the metabolic differences
      between the two and develop a biochemistry of epilepsy, which is differentiated
      from the biochemistry of normal cognition and function. The ketogenic diet is
      successful in controlling or ameliorating a broad spectrum of seizure types and
      etiologies. Perhaps then, common metabolic pathways, independent of seizure type,
      are used in the initiation and spread of electrical seizures. Based on clinical
      experience and limited research data, it would appear that different seizures and
      different epilepsies must have metabolic pathways in common that make them
      susceptible to treatment with a common metabolic therapy. If we could understand
      how the ketogenic diet "works," how changing from a glucose substrate' to a
      ketone body substrate is anticonvulsant, then perhaps a medication could be
      developed that would simulate the biochemical effects of the ketogenic diet. Such
      an approach would be a major departure in the study of the neuroscience of
      epilepsy. The ketogenic diet offers a new paradigm to think about epilepsy and
      its treatment, and perhaps will stimulate new approaches to this still often
      devastating condition.

PMID- 9265975
TI  - Attention-deficit/hyperactivity disorder.
AB  - In this chapter we have reviewed the diagnosis and management of attention
      deficit disorder, focusing particularly on the role of stimulant therapy in ADHD.
      Hisorical review suggests that ADHD has roots that extend back almost a century.
      The definition of ADHD is based on inclusion and exclusion criteria that are
      established by history and reflect behavioral concerns. Attention
      deficit/hyperactivity disorder is a chronic disorder affecting the child's home,
      school, and community life. The primary symptoms of the disorder manifest a
      developmental pattern: activity diminishes while attentional deficits persist.
      Major sources of concern are the secondary and often more resistant problems of
      learning difficulties, behavioral problems, lack of peer acceptance, and low self
      esteem. An often frustrating and perplexing characteristic of the disorder is its
      marked variability-over time, across situations, and within the same child and
      similar situations. Educational management represents an important priority and
      often forms the cornerstone of all other therapies, nonpharmacologic or
      pharmacologic. Cognitive-behavioral therapies represent the most widely used
      alternative to pharmacotherapy. Although the effects of CBT alone are
      disappointing, recent studies suggest that such therapies may provide a useful
      adjunct to pharmacotherapy and may be helpful when children are tapered off
      medication. Psychotherapy, or a combination of psychotherapy and medication
      (termed multimodality therapy), may also be useful. Pharmacotherapy for ADHD
      originated almost 60 years ago, and at this time the ameliorative effects of
      medications in ADHD are well established. The general skepticism of experienced
      clinicians, coupled with a climate where parents are reluctant to medicare
      children, serves to limit their use except where indicated. Although the effects
      of stimulants on attention and activity seem well established, effects on
      cognition, conduct, and social behavior are more controversial. Within recent
      years, a great deal has been learned about the pharmacokinetics of stimulants in
      children with ADHD, providing a rational basis for administration. It is also
      clear that side effects are minimal, the most serious being the possibility of
      the emergence of tics. Whereas stimulants are clearly the most effective agents,
      other agents, including antidepressants, may also be effective. Recent advances
      may now provide an opportunity to better understand the neural and molecular
      basis for ADHD. Recent advances in imaging technology, particularly fMRI, offer
      an opportunity to examine the neural basis of ADHD, and advances in genetics may
      provide clues to its etiology.

PMID- 9265976
TI  - Inherited surfactant protein-B deficiency.

PMID- 9265977
TI  - Periodic syndromes of childhood.
AB  - Periodic syndromes of childhood comprise a large group of disorders that require
      long-term follow-up to be diagnosed. Several disorders have fixed rhythmicity and
      are therefore identified more easily. Other disorders are usually diagnosed after
      a prolonged follow-up and exclusion of other more common childhood diseases. In
      general, most of the periodic fever syndromes have a benign prognosis, and their
      symptomatology tends to improve in the long term. Periodic syndromes without
      fever or chronic pain syndromes constitute not only a diagnostic dilemma but also
      a therapeutic challenge. A general diagnostic approach to the periodic syndromes
      is outlined in Figure 1.

PMID- 9265978
TI  - Infectious complications following trauma in children.

PMID- 9265979
TI  - Use of animal models in pediatric research.

PMID- 9265980
TI  - Children, medicine, religion, and the law.

PMID- 9265981
TI  - Advances in pediatric pharmacology and toxicology.

PMID- 9265982
TI  - Who benefits from immunotherapy?

PMID- 9265983
TI  - Development of atopy in childhood.

PMID- 9265984
TI  - Efficacy of specific immunotherapy in allergic asthma: myth or reality?

PMID- 9265985
TI  - Evaluation of the prevalence of skin prick test positivity to Alternaria and
      Cladosporium in patients with suspected respiratory allergy. A European
      multicenter study promoted by the Subcommittee on Aerobiology and Environmental
      Aspects of Inhalant Allergens of the European Academy of Allergology and Clinical
      Immunology.

PMID- 9265986
TI  - Immunohistochemical analysis of late local skin reactions during rush venom
      immunotherapy.
AB  - During rush venom immunotherapy (VIT), about 65% of patients develop large local
      reactions (LLR) at the application site that last for at least 24 h. However, LLR
      subside during long-term treatment. To learn more about the provenance of
      infiltrating cells in late, local skin reactions during VIT, we analyzed the skin
      infiltrates of 23 Hymenoptera venom (HV)-allergic patients. Punch biopsies were
      obtained 24 h after s.c. injection of HV allergens from 23 HV-allergic patients
      and five nonallergic controls. Seven patients did not show LLR at the beginning
      of VIT. Ten patients had LLR when the dose of HV allergens was increased. Six
      patients showed reduced LLR after long-term treatment. Immunoenzymatic labeling
      of the cryostal sections with a panel of monoclonal antibodies was performed by
      the APAAP method. S.c. application of HV allergens induced a perivascular and
      periadnexial cutaneous mononuclear cell infiltrate consisting mainly of CD4+,
      CD45RO+; and HLA-DR+ cells in patients without clinically apparent LLR. In
      contrast, LLR were associated with a significant increase in total cells, CD4+
      cells, CD8+ cells, CD11c+ cells, EG2+ cells, NP57+ cells, HLA-DR+ cells, CD45RO+
      cells, CD45RA+ cells, CD23+ cells and CD25+ cells (P < 0.001). Decreased LLR
      after long-term VIT was correlated with a significantly reduced recruitment of
      CD4+ cells, EG2+ cells, and CD23+ cells as compared to LLR in the course of dose
      increases (P < 0.05), whereas the number of CD8+ cells, CD11c+ cells, NP57+
      cells, and CD25+ cells remained high. Our data suggest that s.c. injections of HV
      allergens attract CD4+ helper T cells, of both the naive (CD45RA+) and memory
      (CD45RO+) phenotypes, to the allergen application site. LLR represent delayed
      allergic rather than toxic reactions to HV components and might be relevant to
      the development of clinical protection during VIT.

PMID- 9265987
TI  - Sensitization to Blomia kulagini in a general population of a subtropical region
      of Spain (Canary Islands).
AB  - The Blomia genus has been described as allergenic in man. The present study aimed
      to assess the prevalence of B. kulagini sensitization in a large population of
      allergic subjects without occupational exposure in a subtropical region (Canary
      Islands, Spain). Secondarily, a new standardized B. kulagini extract was
      evaluated. The study population comprised 207 patients. RAST for B. kulagini was
      positive in 76.2% of patients, and 47 of them were selected for the biologic
      standardization. When the prick test was performed with the nonstandardized
      extracts, results were positive in 76.6%, whereas when the test was repeated with
      the standardized extract, sensitivity rose to 95.7%. The conjunctival provocation
      test was positive in 78.3% of 46 evaluated patients. The bronchial provocation
      test was positive in 18 sensitized patients and negative in five controls. In
      conclusion, B. kulagini is an important cause of sensitization among the
      occupationally unexposed population of the studied area and should be included in
      allergy diagnostic tests. For reliable prick tests, the use of standardized
      extracts is mandatory.

PMID- 9265988
TI  - Neonates at risk of atopy show impaired production of interferon-gamma after
      stimulation with bacterial products (LPS and SEE)
AB  - Recent studies demonstrate reduced interferon-gamma (IFN-gamma) secretion in
      neonates who became atopic later in life. The underlying pathomechanism is still
      unknown. We therefore examined the effects of bacterial products on neonatal IFN
      gamma production acting through different T-cell- or antigen-presenting-cell
      (APC)-stimulating mechanisms: cord-blood mononuclear cells (CBMC) were incubated
      with lipopolysaccharide (LPS), staphylococcal enterotoxin E (SEE), or a
      combination of both and restimulated with PMA and ionomycin. LPS and SEE as
      single stimuli induced IFN-gamma production to the same extent in CBMC of
      neonates with high and low risk of atopy. In contrast, a combination of LPS and
      SEE had a multiplying effect on IFN-gamma secretion only in CBMC of neonates with
      low risk of atopy. Phenotype analysis revealed that only memory T cells showed
      impaired IFN-gamma synthesis (median 3.6% IFN-gamma-producing cells vs 14.2% in
      controls: P < 0.01), whereas IFN-gamma production by naive T cells did not differ
      in either group. Taken together, these results point to the existence of a
      disturbed function of costimulatory mechanisms in neonates at high risk of atopy,
      provoking reduced memory T-cell IFN-gamma production.

PMID- 9265989
TI  - Bronchial hyperresponsiveness, epithelial damage, and airway eosinophilia after
      single and repeated allergen exposure in a rat model of anhydride-induced asthma.
AB  - Bronchial hyperresponsiveness (BHR) and damage of the epithelium, as well as
      eosinophilia in the airway wall, induced by trimellitic anhydride (TMA) in
      sensitized brown Norway rats were studied. Rats were challenged once or seven
      times with aerosol of TMA conjugated to rat serum albumin (TMA-RSA) 3 weeks after
      intradermal TMA sensitization. Airway responsiveness (-log PC300 of acetylcholine
      i.v.) was measured 24 h after allergen challenge. Epithelial lesion and
      eosinophil infiltration in the airway walls were quantified under light
      microscopy, and TMA-specific IgE and IgG in serum were evaluated with ELISA. High
      levels of TMA-specific IgE and IgG were found in all rats in the sensitized
      groups compared to nonsensitized groups (P < 0.001). Repeated allergen challenges
      of 0.03% TMA-RSA for 7 consecutive days enhanced the level of TMA-specific IgG,
      compared to single challenge (P < or = 0.05). Single allergen challenge of 0.3%
      TMA-RSA had a nonsignificant tendency to produce BHR in sensitized rats compared
      to nonsensitized rats (P = 0.06). However, repeated allergen challenges (0.003%
      and 0.03% TMA-RSA for 7 consecutive days) produced significant BHR in sensitized
      rats (P < 0.05). Furthermore, repeated low-dose (0.003%) TMA-RSA challenge
      produced more BHR than a 10 times higher single dose (0.03%) (P < 0.05). Slight
      damage of the airway epithelium was seen in sensitized and repeat-challenged
      groups. However, bronchial eosinophilia was found in the sensitized and single
      challenged groups, but not in nonsensitized nonchallenged, and sensitized repeat
      challenged groups (P < 0.005). We conclude that the brown Norway rat can be
      sensitized with TMA, and that repeated low-dose allergen challenges produce
      slight epithelial damage and BHR which is independent of ongoing eosinophilia in
      the airway wall.

PMID- 9265990
TI  - Ingestive and inhalative allergy to the mushroom Boletus edulis.
AB  - This is the first report on inhalative and ingestive allergy to the common edible
      mushroom Boletus edulis (Be) (English, edible boletus; German, Steinpilz; French,
      bolet; Italian, porcino or boleto) belonging to the class Basidiomycetes. Four
      cases observed in our allergy unit are presented, showing different clinical
      manifestations of this rare allergy: as an occupational problem or life
      threatening anaphylactic reactions after eating Be. In all cases, skin prick-to
      prick tests with raw Be were strongly positive: in three cases, specific IgE
      against Be could be found. The symptoms were reproducible after an inhalation
      challenge test. It is noteworthy that not only can Basidiomycetes cause airborne
      allergy but also that edible mushrooms from this class can cause inhalative and
      intestinal allergy. The two patients with strong anaphylactic reactions
      demonstrate that Be may have great allergenic potential.

PMID- 9265991
TI  - Cetirizine treatment of allergic cough in children with pollen allergy.
AB  - Cetirizine, an antihistamine widely used in the treatment of allergic
      rhinoconjunctivitis, also has antiallergic activity. The present study aimed to
      evaluate cetirizine as a treatment for children with allergic cough due to pollen
      allergy. This was a parallel-group, double-blind, placebo-controlled, randomized
      study. Twenty children with pollinosis were enrolled: they were subdivided into
      two groups receiving a 1-month treatment during the pollen season. The following
      variables were monitored: 1) clinical symptoms and respiratory data (spirometry
      and PEF) evaluated at baseline and at the end of the study by allergists and by a
      daily diary card, and 2) pollen count. This study shows that cetirizine treatment
      reduces cough intensity (P < 0.05) and frequency (P < 0.01). In conclusion,
      cetirizine does clinically improve cough due to pollen allergy.

PMID- 9265993
TI  - Effects of relaxation on the delayed-type hypersensitivity (DTH) reaction to
      diphenylcyclopropenone (DCP).
AB  - Delayed-type hypersensitivity (DTH) reactions to the experimental allergen
      diphenylcyclopropenone (DCP) were measured in four groups, which either trained
      (+) or did not train in relaxation (-) during the sensitization and/or the
      challenge phase. All groups consisted of high and low hypnotic susceptible
      subjects. While there were no differences in erythema, the mean induration of the
      group which trained in relaxation in both the sensitization and the challenge
      phase (+/+) was significantly greater than that of the group which trained in
      relaxation in the challenge phase only (-/+). Significant correlations were found
      between induration and hypnotic susceptibility scores, and between induration and
      degree of perceived relaxation during challenge. High hypnotic susceptible
      subjects experienced a higher degree of perceived relaxation and exhibited
      greater indurative and erythematous DTH reactions to DCP than low hypnotic
      susceptible subjects in all four experimental conditions. Though the mediating
      mechanisms remain unclear, our results suggest that relaxation may affect the DTH
      reaction, and support previous findings of higher psychophysiologic reactivity of
      high hypnotic susceptible subjects.

PMID- 9265992
TI  - Differences in skin-prick and patch-test reactivity are related to the
      heterogeneity of atopic eczema in infants.
AB  - Current data indicate an obvious relation between food allergy and atopic eczema
      in infants. However, diagnostic methods for food allergy need to be supplemented.
      The objective was to study the relevance of food patch testing in the detection
      of food allergy in correlation with oral food challenge and skin prick tests in
      atopic infants. Infants with atopic eczema (n = 113) aged 2-24 months were
      studied. Each patient was subjected to double-blind, placebo-controlled, or open
      cow's milk challenge, and skin prick and patch tests. Polysensitization, as
      judged from skin test results, was common in patients with atopic eczema
      (79/113). Cow's milk challenge was positive in 54/113 infants; reactions were
      immediate in 36/54 and delayed in 18/54. Immediate-type reactions were associated
      with skin prick test positivity and delayed reactions with patch test positivity.
      Altogether 26% of the cow's milk-allergic infants were detected by patch testing
      only. Patch testing improved the accuracy of skin testing in the diagnosis of
      food allergy in infants with atopic eczema, but it needs to be standardized.
      Polysensitization appears to be more common than generally believed among infants
      with atopic eczema.

PMID- 9265994
TI  - Monitoring of disease activity by measurement of inflammatory markers in atopic
      dermatitis in childhood.
AB  - Serum levels of soluble interleukin-2 receptor (sIL-2R), intercellular adhesion
      molecule-1 (ICAM-1), endothelial leukocyte adhesion molecule (ELAM-1), and
      eosinophil cationic protein (ECP) were measured in 20 patients with atopic
      dermatitis before and after 4 days' treatment with prednisolone p.o. as well as
      in 16 healthy, nonatopic controls. Before steroid treatment, patients with atopic
      dermatitis demonstrated significantly higher serum levels of sIL-2R, ICAM-1, and
      ECP than healthy controls (P < 0.001), whereas ELAM-1 levels were not different
      between the groups. After 4 days of steroid treatment, clinical improvement was
      associated with a decrease of sIL-2R (P < 0.003), ICAM-1 (P < 0.004), and ECP
      serum levels (P < 0.003), but ELAM-1 levels remained unchanged. Both serum ECP
      and sIL-2R levels were significantly correlated with disease severity before as
      well as after steroid treatment. Changes of sIL-2R concentrations were strongly
      related to the changes of ECP levels. In addition, changes of serum sIL-2R and
      ECP levels in percentage were correlated with clinical improvement. These results
      indicate that the determination of sIL-2R and ECP serum levels may be useful in
      monitoring disease activity in atopic dermatitis in childhood, especially in
      treatment trials.

PMID- 9265996
TI  - Comments on BU (biologic units)

PMID- 9265995
TI  - Nasal metachromatic cells in infancy in relation to the appearance of atopic
      disease during the first 6 years of life.
AB  - The relationship between the appearance of nasal metachromatic cells (basophils
      and mast cells) during the first 18 months of life and the development of
      respiratory and other allergic diseases up to 6 years of age was studied
      prospectively in 67 children. Follow-up was done at 3, 6, 9, and 18 months and 6
      years. Of the 31 children who had detectable metachromatic cells in the nasal
      mucosa during infancy, 18 had atopic manifestations at 6 years (58%), two were
      probably atopic (6%), and 11 (36%) were nonatopic. The corresponding numbers for
      the 33 children without detectable metachromatic cells during infancy were 10
      atopic (30%), two probably atopic (6%), and 21 nonatopic (64%) at 6 years (P <
      0.05). Children having detectable nasal metachromatic cells at every examination
      were more often allergic than children with no detectable cells at any time
      during the 6-year follow-up period (P < 0.05). In contrast, nasal metachromatic
      cells were equally commonly demonstrated at 6 years in children with and without
      current atopic manifestations. We conclude that metachromatic cells appear at an
      earlier age in the nasal mucosa of atopic than nonatopic infants. The observation
      further supports the existence of a primary immunologic abnormality in atopic
      patients as related to allergic inflammatory responses. The diagnostic efficacy
      of this marker was too low, however, to be clinically useful as a predictor of
      allergy.

PMID- 9265997
TI  - Recurrent localized pustular eruption induced by amoxicillin.

PMID- 9265998
TI  - Occupational asthma caused by cacao.

PMID- 9265999
TI  - 6-Methylprednisolone-induced bronchospasm.

PMID- 9266000
TI  - Vaginal bleeding--a rare complication of immunotherapy.

PMID- 9266001
TI  - Rush desensitization with ubiquinone.

PMID- 9266002
TI  - Systemic reactions to clotiazepam.

PMID- 9266003
TI  - Low serum M-CSF levels are associated with unexplained recurrent abortion.
AB  - PROBLEM: The purpose of this study was to determine whether the serum macrophage
      colony stimulating factor (M-CSF) level is associated with early pregnancy loss
      in unexplained recurrent spontaneous abortion (RSA) patients. METHOD: We
      therefore compared preconceptional serum M-CSF levels between unexplained RSA
      patients and controls. The former comprised 44 bed-rest therapy patients and 43
      intradermal immunization (IDI) patients receiving paternal lymphocyte therapy,
      who had experienced two and three or more consecutive first-trimester pregnancy
      losses, respectively. The controls were 46 healthy non-pregnant women. We also
      prospectively studied the association between M-CSF levels during pregnancy and
      adverse pregnancy outcomes. Sera from a total of 31 pregnant women, including 16
      of the bed-rest therapy group and 15 of the IDI therapy group, were collected at
      the 4th, 6th, and 8th gestational weeks and were measured for M-CSF levels, using
      the enzyme-linked immunoadsorbent assay (ELISA) method established by Hanamura et
      al. RESULTS: Serum M-CSF levels were significantly lower in the non-pregnant RSA
      patients (460.0 +/- 185.6 U/ml; mean +/- SD) than in the control group (726.5 +/-
      134.0 U/ml) and also were lower at the 8th, but not the 4th or 6th gestational
      week in those patients of both the bed-rest and IDI therapy groups whose outcome
      was pregnancy failure. CONCLUSION: Thus a low level of serum M-CSF was found to
      be associated with unexplained recurrent pregnancy loss in both the
      preconceptional and conceptional phases. These results raise the possibility that
      M-CSF may play an important role in the maintenance of pregnancy and that it can
      be used as a parameter for determining individuals at risk.

PMID- 9266004
TI  - Evidence that the expression of progesterone-induced blocking factor by maternal
      T-lymphocytes is positively correlated with conception.
AB  - PROBLEM: To compare the expression by T-lymphocytes of an immunomodulatory
      protein known as progesterone-induced blocking factor (PIBF) in conception versus
      non-conception cycles even when there has been definite fertilization and embryo
      formation. METHOD: PIBF expression on T lymphocytes was measured using an
      immunohistochemical method with a PIBF-specific polyclonal antibody. These levels
      were determined in patients undergoing three types of therapy: non-in vitro
      fertilization (IVF), IVF-embryo transfer (ET), and frozen ET. Sera were drawn 12
      days from ovulation in non-IVF cycles or 9 days after ET and were assayed for
      PIBF and beta human chorionic gondotropin. Comparison of the frequency of
      lymphocyte expression of PIBF in pregnant versus non-pregnant women were made.
      RESULTS: PIBF was detected in 29.5% of non-pregnant women and 52.5% of pregnant
      women. There were no differences in PIBF levels by therapy used in non-pregnant
      cases or in the pregnant group. CONCLUSION: These data are consistent with the
      hypothesis that maternal expression of PIBF in T-lymphocytes soon after
      trophoblast invasion may depend on successful implantation.

PMID- 9266005
TI  - Perforin-expressing lymphocytes in peripheral blood and decidua of human first
      trimester pathological pregnancies.
AB  - PROBLEM: We have shown previously that the decidua of first-trimester human
      pregnancy is heavily infiltrated with perforin-positive cells. The aim was to
      detect expression of perforin in both decidual lymphocytes (DL) and peripheral
      blood lymphocytes (PBL) in the first trimester of pathological pregnancies:
      Anembryonic pregnancy and missed abortion. METHOD: Decidual tissue from a normal
      pregnancy group and from pathological pregnancies was obtained by vaginal
      curettage. Perforin (an intracellular antigen) and the cell surface antigens CD3,
      CD4, CD8, CD16, CD56, CD11c, and CD45RA were quantified simultaneously by flow
      cytometric analysis. RESULTS: In the missed abortion group, we found: 1) a
      relative decrease in the frequency of both CD4+P+ cells and CD56+P+ cells as well
      as the mean fluorescence intensity for perforin; 2) a relative increase of
      CD16+P+ PBL cells; and 3) a relative increase of CD4+ cells in PBL compared with
      anembryonic pregnancy and normal pregnancy. There was also a significant relative
      decrease in the proportion of CD4+ and CD8+ cells among perforin-positive PBL in
      both anembryonic pregnancy and missed abortion. CONCLUSION: Our results show that
      significant decreases in the prevalence of perforin-positive lymphoid cells,
      their subpopulations, and mean fluorescence intensity for perforin are associated
      with pregnancy failure.

PMID- 9266006
TI  - Growth-regulated alpha expression in human preovulatory follicles and ovarian
      cells.
AB  - PROBLEM: Around the time of ovulation the number of neutrophils increases in the
      theca of the leading follicle. We hypothesized that growth-regulated alpha (GRO
      alpha), a neutrophil chemoat-tractant/activating factor, may be a modulator of
      periovulatory neutrophil chemotaxis. METHOD: GRO alpha levels were measured in
      follicular fluids (n = 61). Granulosa-lutein and ovarian stromal cells were also
      cultured. After experimental paradigms, GRO alpha mRNA was evaluated by Northern
      analysis, GRO alpha in follicular fluids, and culture supernatants were
      quantified using ELISA. RESULTS: In follicular fluids the mean pre-human
      chorionic gonadotropin (hCG) GRO alpha level was 51 +/- 24 (+/- SEM) pg/ml, post
      hCG it was 210 +/- 20 pg/ml (P = 0.04). GRO was produced constitutively by
      ovarian stromal and granulosa-lutein cells. Interleukin-alpha (IL-1 alpha) and
      tumor necrosis factor-alpha (TNF-alpha) further stimulated GRO alpha production.
      Treatment of stromal cells with hCG also stimulated GRO alpha production.
      CONCLUSION: GRO alpha is a constituent of periovulatory follicular fluid. Ovarian
      stromal and granulosa-lutein cells express the GRO alpha mRNA and produce the
      protein. The regulation of GRO alpha by cytokines and hCG suggests that GRO alpha
      may play a role in the process of ovulation.

PMID- 9266007
TI  - Identification of epitopes of monoclonal antibodies to porcine zona pellucida 3
      beta glycoprotein, a homologue of the mouse/human sperm receptor.
AB  - PROBLEM: Immunization with zona pellucida (ZP) glycoproteins leads to a block in
      fertility with a variable degree of ovarian dysfunction. To avoid autoimmune
      oophoritis, synthetic peptides corresponding to B cell epitope(s) and devoid of
      oophoritogenic T cell epitopes as immunogens have been proposed. The main
      objective of the present study is to define the epitopes recognized by monoclonal
      antibodies (mAbs) generated against porcine ZP3 beta, a homologue of the
      designated primary sperm receptor in mice and humans. METHODS: A multipin
      synthetic peptides approach has been used to map the epitopes recognized by mAbs.
      Dodecapeptides with an overlap of 6 amino acids corresponding to a precursor pZP3
      beta-deduced amino acid sequence (excluding the signal sequence) were synthesized
      on polypropylene pins and were tested for their reactivity with mAbs by enzyme
      linked immunoadsorbent assay (ELISA). The ability of synthetic peptides
      corresponding to the identified epitopes to inhibit the binding of mAbs to pZP3
      beta in a competitive inhibition ELISA was investigated to confirm the above
      findings. RESULTS: Reactivity of the mAbs with the pin-bound peptides in ELISA
      identified epitopes for mAb-451 to EEKLVF (166-171) and mAb-462/470 to FKAPRP
      (250-255) amino acid residues. mAb-30 recognized QPVWQDEGQRLR (23-34) and VICRCC
      (316-321) amino acid residues. Competitive inhibition with synthetic peptides
      encompassing the motifs corresponding to 23-34 and 316-321 for binding of mAb-30
      to pZP3 beta revealed the epitopic domain to be 23-34 amino acids. Synthesis of
      overlapping octapeptides further identified WQDE as the minimum motif for binding
      of mAb-30, and the replacement of one amino acid at a time with glycine revealed
      tryptophan as the critical residue. CONCLUSIONS: Collectively, these results
      describe peptide epitopes that will help in the design of an immunocontraceptive
      vaccine based on synthetic peptides corresponding to pZP3 beta or its homologues
      in other species.

PMID- 9266008
TI  - GRO-alpha in human serum: differences related to age and sex.
AB  - PROBLEM: Human GRO-alpha (GRO-alpha) is a new member of the chemokine family that
      is supposed to play an important role in inflammatory and immune reactions. We
      established a sandwich enzyme-linked immunoassay (ELISA) system with polyclonal
      antibodies against human GRO-alpha and investigated the serum level of healthy
      donors to establish normal ranges for this chemokine in adults. METHODS: GRO
      alpha concentrations were measured cross-sectionally in the sera of 240 healthy
      adults. The variability of serum GRO-alpha levels was also measured in normal
      volunteers, samples from whom were obtained by sequential venipunctures or by a
      small plastic cannula with a heparin-saline lock, to determine short-term
      variability. RESULTS: Whereas there was no difference between the concentration
      of human GRO-alpha from men (logarithmic mean, 77.6 pg/ml, n = 120) and that from
      women with normal menstrual cycles (log mean, 71.6 pg/ml, n = 73), the
      concentration from postmenopausal women (log mean 45.0 pg/ml, n = 31) was lower
      than that from women with normal menstrual cycles (log mean 71.6 pg/ml, n = 73).
      However, we could not detect any significant difference between healthy donors'
      serum levels and those of donors with acute inflammation. Fewer variations were
      recognized in the case of the sequential venipunctures method than in that of the
      heparin-saline lock method. CONCLUSION: We found that the GRO-alpha concentration
      of postmenopausal women was significantly lower than that of women with normal
      menstrual cycles. These results suggest the GRO-alpha serum levels of normal
      healthy women may have some correlation with sex hormones.

PMID- 9266009
TI  - Immunomagnetic isolation of fetal rat gonocytes.
AB  - PROBLEM: An efficient method to obtain highly enriched populations of viable
      gonocytes from rat embryos at Day 18 and Day 20 postcoitum (pc) is described.
      METHOD: Single-cell suspensions with high cell yield were obtained by a
      collagenase/ trypsin digestion of the decapsulated testis. The gonocytes were
      purified by a direct immunoseparation technique, using magnetizable beads coated
      with rat anti-mouse immunoglobulin M (IgM) and a monoclonal antibody 4B6.3E10,
      which specifically reacted with a differentiation antigen on the fetal germ
      cells. RESULTS: Populations of 8.3 +/- 2.7 (x10(3); 18 days pc) or 1.2 +/- 0.25
      (x10(4); 20 days pc) viable gonocytes per testis with purities of 91 +/- 6.5% and
      92 +/- 4.3%, respectively, as determined by Nomarski microscopy were obtained.
      CONCLUSION: The cells were successfully used for culture studies and as starting
      material for the investigation of gene expression.

PMID- 9266010
TI  - Estradiol down-regulates LPS-induced cytokine production and NFkB activation in
      murine macrophages.
AB  - PROBLEM: In vivo and in vitro studies have indicated that estradiol can affect
      cytokine production in different cell types. This study examines whether
      estradiol affects inflammatory cytokine production by murine splenic macrophages.
      METHODS: Mouse splenic macrophages were first treated with 17 beta-estradiol,
      followed by lipopolysaccharide (LPS) stimulation. The production of cytokines by
      macrophages with or without estradiol treatment was determined at both the
      protein and mRNA levels. The nuclear factor-kB (NFkB) activity of activated mouse
      splenic macrophages was also evaluated by electrophoretic mobility shift assay.
      RESULT: Our results show that 17 beta-estradiol decreases LPS-induced IL-1 alpha,
      IL-6, and TNF-alpha production but not IL-10, IL-12, and macrophage inflammatory
      protein (MIP) production by splenic macrophages. Furthermore, inhibition of
      cytokine production by 17 beta-estradiol was associated with a decreased LPS
      induced NFkB-binding activity. CONCLUSION: Because cytokines are important
      mediators of immune function, the alteration of cytokine production by 17 beta
      estradiol may thus have a profound effect on the outcome of immune response
      during inflammation.

PMID- 9266012
TI  - Cultural relativism and cultural diversity: implications for nursing practice.
AB  - This article examines the doctrine of cultural relativism in nursing practice. To
      introduce the issue, an overview of the intellectual history of cultural
      relativism is presented. The academic themes of the debate surrounding cultural
      relativism are illustrated with an example of the social controversy in France
      involving cultural relativism as used to defend the practice of female genital
      excision among immigrant communities. The dilemma faced by nursing in making
      cross-cultural judgments is then examined in the light of the academic and social
      debates. The article concludes with a theoretical resolution of the issue of
      cultural relativism for nursing practice that is based on hermeneutic philosophy.

PMID- 9266013
TI  - Advancing discourse on health promotion: beyond mainstream thinking.
AB  - Attention must be redirected toward health promotion as nursing evaluates the
      goal of health for all. Confusion regarding health promotion behavior is
      illustrated by terms with diverse meanings and uses. In a process of critical
      analysis, five multidisciplinary experts in health promotion responded to a
      survey targeting the distinction of health promotion, health promotion behavior,
      health protection behavior, disease prevention behavior, preventive health
      behavior, health behavior, and healthy lifestyle. Descriptors of health promotion
      were derived from a multidimensional conception of well-being. Disagreement
      existed concerning health protection and health behavior. Nursing interventions
      are linked to reflective discourse regarding health promotion behavior.

PMID- 9266011
TI  - [Unusual vascular lesions in the course of a colonic leishmaniasis in an HIV
      positive patient].
AB  - Patients with acquired immunodeficiency syndrome are often susceptible to
      atypical dissemination of visceral leishmaniasis. Digestive localizations seem to
      be relatively frequent. Colonic localizations reported in the literature are
      endoscopically normal or show superficial mucosal lesions. We describe an
      original case of leishmaniasis associated with a colonic pseudotumoral stenosis
      with perforated ulcer penetrating in the mesocolon. Striking inflammation of
      mesenteric blood vessels, even far from the ulcer, suggested an ischemic
      mechanism for the colonic stenosis. These findings raise the hypothesis that
      vasculitis is secondary to mucosal parasitic infection.

PMID- 9266014
TI  - A multiparadigm approach to nursing.
AB  - Nursing theory development has made good progress in differentiating the domain
      of nursing from medicine; many of these theories are categorized as holistic
      theories. Nursing classification systems are also being developed to organize
      extant nursing practice. The dissonance between the two has been one of the most
      difficult contemporary issues for the leadership of nursing. A framework is
      proposed that would account for these disparate approaches. This proposed
      framework for the domain of healing is in keeping with the metaparadigm of health
      and uses a multiple paradigm approach. Nursing interventions are discussed in
      relation to the framework. It invites a dialogue in keeping with the scholarship
      of holism. Practice and scholarship implications are discussed.

PMID- 9266015
TI  - Experiencing the whole.
AB  - This personal essay describes the author's theoretical and methodological journey
      in her quest for understanding of wholeness as a basic concept of the discipline
      of nursing. She asserts that wholeness, seen as pattern and meaning of the life
      process, is not amenable to external measurement and control, but is learned from
      within by a hermeneutic dialectic process with clients. The emphasis on the
      evolution of undivided wholeness is consistent with a unitary-transformative
      paradigm of the discipline.

PMID- 9266016
TI  - Measuring problem behaviors in dementia: developing a methodological agenda.
AB  - As many as 90% of persons with dementing illness demonstrate problem behaviors
      that range from repetitive verbalizations, agitation, and wandering to verbal and
      physical aggression toward self and others. Reliable and accurate measurement of
      these behaviors is crucial for tracking illness progression; for monitoring the
      effects of pharmacologic and behavioral interventions; and for continued
      investigation into the correlates of caregiver stress, burden, and coping.
      However, there is no single, universally accepted measure or methodology for
      operationalizing problem behaviors, and variations in definition and measurement
      across studies complicate drawing meaningful conclusions about these behaviors.
      This article is an overview of five factors that have complicated accurate and
      dependable measurement of problem behaviors in dementia: the shifting domain of
      problem behaviors, slippage across research constructs, unexplored rater bias,
      scoring bias, and the absence of benchmarking studies. A methodological agenda is
      discussed for future investigations in this rapidly growing area of
      gerontological research.

PMID- 9266017
TI  - Psychiatric nursing: epistemological contradictions.
AB  - This theoretical analysis begins from the premise that the medical specialty of
      psychiatry is practically and ideologically dominant in relation to psychiatric
      nursing. To explicate some difficulties within psychiatric nursing from a
      therapeutic perspective, crucial 19th century European psychiatric
      epistemological developments are outlined. The article addresses the contemporary
      problematic of nursing agency in the face of mainstream psychiatry's focus on
      physical treatments. It is argued that there are intrinsic contradictions for
      present-day humanistic psychiatric nursing given the theoretical and practical
      power of the materialist medical model.

PMID- 9266018
TI  - Menopause on the Internet: building knowledge and community on-line.
AB  - Computers are ubiquitous throughout the developed world. Diverse discourses
      address the pros and cons of using this technology in higher education. Nursing
      has extensively used informatics but has not, as yet, been involved to any extent
      in teaching on the Internet. I argue that nurse educators should use computer
      technology to present substantive and rigorous courses that deal with complex
      issues, using menopause as an example. A for-credit menopause course I taught via
      e-mail is used to illustrate the possibility of building knowledge and a sense of
      community on the Internet.

PMID- 9266019
TI  - Cytokine expression and antigen-presenting capacity of 4F7+ dendritic cells
      derived from dermis, spleen, and lymph nodes.
AB  - We took advantage of the recently generated 4F7 mAb, which recognizes an epitope
      expressed on dendritic cells (DC) from different tissues, to freshly isolate and
      positively sort for these cells and to characterize their cytokine pattern and
      antigen-presenting capacity in comparison with epidermal Langerhans cells (LC).
      RT-PCR and Northern blot analyses demonstrated constitutive mRNA expression of
      MIP-1 gamma, MIP-1 alpha, C10, and IL-1 beta in both 4F7+ DC and LC.
      Lipopolysaccharide (LPS) treatment resulted in the upregulation of mRNA
      expression of all four cytokines and in a newly detected signal for TNF alpha.
      Immunoblot analysis showed constitutive secretion of MIP-1 gamma, with LPS
      treatment resulting in the upregulation of IL-1 beta production and in newly
      detected TNF alpha secretion. 4F7+ DC were also shown to express mRNA for the
      common gamma chain receptor of IL-2 and for the receptor of IL-4. Finally, we
      demonstrated freshly isolated 4F7+ DC to be equivalent to freshly isolated LC in
      their capacity to present alloantigen in the mixed leukocyte reaction (MLR) and
      to process and present purified protein derivative (PPD) to Th1 and Th2 clones.
      We conclude that 4F7 is a useful marker for positively sorting DC from dermis,
      spleen, and lymph nodes. Regardless of tissue source, 4F7+ DC exhibit uniform
      cytokine and antigen-presenting capacity profiles that mimic the properties of
      freshly isolated epidermal LC.

PMID- 9266020
TI  - The expression of interleukin-8 receptor in untreated and treated psoriasis.
AB  - The expression of IL-8 in psoriasis has been clearly shown with the use of
      immunocytochemical, RT-PCR and in situ hybridization methods. The presence of its
      ligand, the IL-8 receptor, has been demonstrated by the RT-PCR technique. We
      report here a study of the expression of both IL-8 type A and B receptors by
      immunohistochemical techniques, using one polyclonal and four monoclonal
      antibodies. By this technique, we found that the neutrophilic granulocytes
      express the IL-8 type A receptor, whereas the IL-8 type B receptor was present on
      the keratinocytes. The type B receptor on the keratinocytes was localized in the
      suprabasal layers of the epidermis. Following therapy, the expression of the IL-8
      type B receptor on the keratinocytes was reduced. This could suggest that IL-8 in
      psoriasis is involved in the disturbed differentiation rather than in
      proliferation, probably via an autocrine loop.

PMID- 9266021
TI  - The demonstration of serum interleukin-8 and superoxide dismutase in Adamantiades
      Behcet's disease.
AB  - Serum interleukin-8 (IL-8) production was measured in 43 Adamantiades-Behcet's
      disease (A-BD) patients and in 46 healthy volunteers using a sandwich enzyme
      linked immunosorbent assay (ELISA). The mean serum IL-8 level of the patients
      (14.6 +/- 3 pg/ml) was significantly higher than that of controls (10.8 +/- 3
      pg/ml, P < 0.05). Since IL-8 is known to have proinflammatory properties, it may
      play some role in the pathogenesis of A-BD. We also investigated the activity of
      serum superoxide dismutase (SOD) in the 43 patients with A-BD and in the 46
      healthy volunteers. Serum SOD activity was markedly increased in the patients
      with A-BD (13.1 +/- 3%), especially in active A-BD, compared with that in the
      healthy volunteers (6.7 +/- 3%, P < 0.01). Our results suggest the involvement of
      IL-8 and SOD in the pathogenesis of A-BD as seen in other inflammatory diseases.

PMID- 9266022
TI  - Differential expression of the HsKin17 protein during differentiation of in vitro
      reconstructed human skin.
AB  - In eukaryotic cells, various proteins homologous to the E. coli RecA protein are
      involved in the elimination of DNA damage. These proteins contribute to the
      repair of double-strand breaks and to genetic recombination. The mouse Kin17
      protein is recognised by antibodies directed against the RecA protein. Kin17 has
      a zinc-finger domain allowing binding to curved DNA stretching over illegitimate
      recombination junctions. In the present study, we identified the human
      counterpart of the mouse Kin17 protein (named HsKin17) in skin cells. We employed
      an in vitro reconstructed skin model composed of an epidermal sheath lying on a
      dermal matrix with human fibroblasts embedded in rat collagen type I. The
      maturation programme (proliferation versus differentiation) of keratinocytes was
      highly dependent on stromal cells. Immunohistochemical staining of frozen
      sections obtained from skin specimens was monitored by an interactive laser
      cytometer. In this way we analysed protein levels in both dermal and epidermal
      compartments. After having characterised the epithelium, we focused our attention
      on HsKin17 expression. We detected HsKin17 in human keratinocytes. HsKin17
      protein levels increased in proliferating epithelial keratinocytes after 7 days
      of culture. After 2 weeks of culture, epidermal sheaths acquired most of the
      differentiated features of mature epithelium. At this time, HsKin17 protein
      dropped below measurable levels in the stratum corneum, and diminished in
      nucleated cells. This study showed that HsKin17 is expressed in human
      reconstructed epithelium under conditions of hyperproliferation.

PMID- 9266023
TI  - Hair cycle-dependent expression of a nonspecific cross reacting antigen (NCA)
      50/90-like molecule on follicular keratinocytes.
AB  - We found a carcinoembryonic antigen (CEA)-related antigen to be strongly
      expressed on a subset of follicular keratinocytes in normal human skin. The
      antigen was characterized immunohistochemically using a panel of antibodies
      against human CEA and CEA-related molecules. The expression of the antigen was
      studied in different phases of the hair cycle as well as in different hair types.
      Immunohistochemically, the antigen resembled the nonspecific crossreacting
      antigen (NCA) NCA-50/90 rather than true CEA. Its expression was limited to the
      innermost cells of the lowest segment of hair follicles in the catagen/telogen
      phases, being detected only where the hair shaft was attached to the epithelial
      hair sac in these phases. The same results were obtained for all hair types, i.e.
      terminal, vellus and intermediate hair. Coexpression of the antigen with both
      involucrin and differentiation-associated cytokeratins was noted in the cells in
      additional studies attempting to identify the exact subpopulations of follicular
      keratinocytes expressing the antigen in comparison with the expression of other
      functional markers. However, involucrin and the cytokeratins were also expressed
      in the upper segments of anagen as well as catagen/telogen hair follicles. Our
      findings strongly suggest that an NCA-50/90-like molecule is expressed cyclically
      on the innermost cells in the lowest segment of the outer root sheath only in
      catagen/telogen hair follicles. The cyclical expression in this specific subset
      of follicular keratinocytes only, in which the epithelial hair sac is attached to
      the hair shaft, may be associated with the stability of the attachment through
      the adhesive or, conversely, the repulsive function of CEA-related molecules,
      both of which have recently been proposed.

PMID- 9266024
TI  - IFN-gamma-induced HLA-DR but not ICAM-1 expression on cultured dermal papilla
      cells is downregulated by TNF-alpha.
AB  - The immune response present in untreated alopecia areata (AA) is characterized by
      overexpression of ICAM-1 and MHC molecules on dermal papilla cells of affected
      hair follicles and by a distinct cytokine pattern. After successful treatment
      with the potent contact allergen diphenylcyclopropenone (DCP), adhesion molecules
      are downregulated and a reversed pattern of cytokines is expressed. To determine
      which cytokines may be involved in this process we studied the expression and
      modulation of ICAM-1 and MHC class I and II molecules on cultured dermal papilla
      cells. Scalp biopsies were obtained from healthy donors and dermal papillae were
      isolated. The cells were treated with various cytokines and prostanoids. The
      surface molecules were labeled with FITC-conjugated antibodies, and the
      expression levels were quantified by FACScan analysis. Incubation with IFN-gamma
      led to a time-dependent upregulation of the surface molecules studied. IL-1 beta
      and TNF-alpha synergistically increased the expression of ICAM-1, but they failed
      to induce MHC molecules. However, both cytokines significantly reduced the IFN
      gamma-induced HLA-DR expression. Pretreatment of cells with the cyclooxygenase
      inhibitor diclofenac, prostanoids, IL-10 or TGF-beta 1 did not alter the
      constitutive or IFN-gamma-elicited expression of surface molecules. A
      neutralizing anti-IL-1 beta-antibody did not affect any cytokine-induced changes.
      We conclude that with regard to surface molecules we can partly initiate in vitro
      the situation of AA in vivo. Moreover, our results suggest that TNF-alpha, which
      is markedly increased under DCP treatment, might be an effector of the
      therapeutic response in AA.

PMID- 9266026
TI  - Downregulation of decorin expression in dermal fibroblasts by interleukin-4.
AB  - Decorin, a chondroitin/dermatan sulphate proteoglycan, plays an important role in
      the assembly of extracellular matrix components. In this study, we investigated
      the influence of interleukin-4 (IL-4) on the expression of decorin and sulphated
      glycosamino-glycans (GAGs) in cultures of human skin fibroblasts. IL-4 inhibited
      the expression of decorin mRNA and its core protein synthesis. IL-4 stimulated
      dermatan sulphate but decreased chondroitin sulphate synthesis without altering
      the total amount of sulphated GAGs. IL-4 had no effect on the initiation activity
      of the dermatan sulphate and chondroitin sulphate chains, as evaluated by the
      effect of exogenous beta-xyloside that acts as an artificial chain initiator for
      dermatan sulphate and chondroitin sulphate biosynthesis. Type I collagen mRNA
      levels and protein synthesis were increased by this IL-4. Therefore, the effects
      of IL-4 on decorin and GAGs as well as type I collagen may have important
      implications for wound healing and for the treatment of several fibrosing
      diseases.

PMID- 9266025
TI  - Expression of the retinoid-inducible polypeptide, midkine, in human epidermal
      keratinocytes.
AB  - Midkine (MK) is a retinoid-inducible and potent cell growth/differentiation
      factor active during mouse embryogenesis. We studied MK expression in various
      cell strains established from the skin. MK and its mRNA were detected in cultured
      keratinocytes but not in melanoma cell lines or dermal fibroblasts by both
      Western blot analysis and reverse transcription-polymerase chain reaction (RT
      PCR). Treatment of cultured keratinocytes with retinoic acid (10(-5) M, 24 h)
      resulted in an increase in the level of MK mRNA. When added to cultured
      keratinocytes, MK stimulated cell proliferation fourfold. Immunohistochemistry
      revealed MK to be present at the epidermal-dermal junction in embryonic mouse
      skin and in normal human skin. The limited expression of MK in epidermal
      keratinocytes indicates that this polypeptide may be involved in the
      differentiation/proliferation of keratinocytes.

PMID- 9266027
TI  - Decorin and glycosaminoglycan synthesis in skin fibroblasts from patients with
      systemic sclerosis.
AB  - We investigated the expression of decorin and the synthesis of sulphated
      glycosaminoglycans (GAGs) in cultured fibroblasts from patients with early-stage
      systemic sclerosis (SSc). Decorin mRNA levels were 1.8-fold higher in SSc
      fibroblasts than in control fibroblasts. SSc fibroblasts also produced 2.3-fold
      more decorin core protein and 2.2-fold more sulphated GAGs including dermatan
      sulphate and chondroitin sulphate. Newly synthesized GAGs, in the presence of p
      nitrophenyl beta-xylopyranoside, which elongates dermatan sulphate and
      chondroitin sulphate as an initiator, were increased tenfold and were mainly
      composed of dermatan sulphate and chondroitin sulphate. The rate of stimulation
      by the beta-xyloside was similar in SSc and control fibroblasts. These results
      suggest that the increased amount of dermatan/chondroitin sulphate in SSc
      fibroblasts reflects an enhanced expression of decorin core protein. Type I
      collagen mRNA levels in SSc fibroblasts were also increased together with its
      synthesis. Therefore, our results indicate that an altered decorin and collagen
      production may affect the organization of collagen fibres and the fibrotic
      process observed in patients with SSc.

PMID- 9266028
TI  - Molluscum contagiosum virus grows in human skin xenografts.

PMID- 9266029
TI  - Modulation by elastin peptide VGVAPG of cell proliferation and elastin expression
      in human skin fibroblasts.

PMID- 9266030
TI  - A keratin K5 mutation (Leu 463-->Pro) in a family with the Weber-Cockayne type of
      epidermolysis bullosa simplex.

PMID- 9266031
TI  - Injury panorama and medical consequences for 1158 persons assaulted in the
      central part of Stockholm, Sweden.
AB  - This retrospective study describes assaults, type of trauma, injury panorama, the
      abbreviated injury scale score and medical consequences for 1158 assaulted
      persons. All patients were examined by surgeons at the Emergency Department,
      Sabbatsberg's Hospital, Stockholm, Sweden, which is open around the clock. The
      police were not notified. The study group included all assaulted patients who
      attended and were examined at the Emergency Department from 1 April 1992 to 31
      March 1993: 84% men and 16% women. Their median age was 25 years (range 13-86
      years). Sixty-eight percent arrived at the Emergency Department between 11 p.m.
      and 4 a.m. In 44% the hospital staff registered in the case notes that the
      victims were drunk. Blunt trauma of low-energy type predominated, 44% were hit by
      fists and 30% by kicks. Penetrating trauma occurred in 10% of the assaults (knife
      8%), and a combination of blunt and/or cutting trauma (bottle/ glass) in 10%.
      Eighty-two percent of the victims suffered an injury to the head, resulting in
      concussion in 116 cases, 4 skull fractures, 1 intracerebral contusion, 74
      fractures of nose bones, 17 fractures of other face bones, and 6 mandible
      fractures. Two persons died because of knifestab wounds. Eighty-two percent of
      the victims had minor injuries, and 16% had moderate injuries according to the
      score on the Abbreviated Injury Scale (AIS). The present study shows that assault
      in the central part of Stockholm, Sweden, is mainly a problem involving young
      men, especially late in the evening, and that many of the victims are drunk.
      Injuries to the head due to low-energy trauma are the most common (hit by fists
      and kicks), but severe injuries seldom occur.

PMID- 9266032
TI  - Unusual locations of osteoarticular tuberculosis.
AB  - Tuberculosis continues to occur frequently in some underdeveloped regions. Bone
      and joint tuberculosis is less common than the pulmonary form. Fourteen cases of
      bone and joint tuberculosis in unusual locations are presented. Tuberculostatic
      treatment and surgical approach were associated in all the patients. In 6 cases
      an arthrodesis of the affected joint was carried out. A surgical debridement was
      done in 6 patients and a needle biopsy in 2 patients in order to obtain samples
      for pathology and bacteriology. Twelve of the 14 patients recovered. One patient
      who was affected by atlanto-axial tuberculosis died within the immediate
      postoperative period. A second one affected by the acquired immunodefiency
      syndrome died 4 months after surgery.

PMID- 9266033
TI  - The subjective shoulder rating system.
AB  - We developed a subjective shoulder rating system (SSRS) and tested its
      reliability against a recognized system (Constant-Murley Score) and a four-point
      verbal rating scale in 200 patients (mean age 43 years, range 18-71 years; 83
      women and 117 men; 48 anterior shoulder reconstructions, 123 subacromial
      decompressions, 29 manipulations under anesthesia). Within the study period of 1
      year, patients completed the SSRS preoperatively and at 1 and 2 weeks, also at 3,
      6, and 12 months. The examination according to the Constant-Murley Score was
      performed preoperatively and at 3 and 12 months. Linear regression showed a
      highly significant correlation between the SSRS and the Constant-Murley Score (r
      = 0.83, n = 592, P < 0.001). Ninety-seven percent of the SSRS forms were
      completed and returned. The average time to complete the SSRS form was 55 s
      (range 20-310 s) as compared with an experienced examiner requiring an average of
      410 s (range 190-720 s) to complete the Constant-Murley Score. The time
      difference was highly significant (P < 0.001).

PMID- 9266034
TI  - Use of adriamycin-impregnated methylmethacrylate in the treatment of tumor
      metastases in the long bones.
AB  - Internal fixation or endoprosthetic replacement of a long bone metastatic lesion
      was performed using adriamycin-containing bone cement (methylmethacrylate) after
      resection or curettage of the lesion in 25 patients (27 limbs). Survival rate,
      limb function, and local recurrence rate were retrospectively evaluated in this
      patient cohort. Survival rate was 53% at 12 months and 30% at 24 months, which
      was better than in previous reports. One patient showed local recurrence
      radiographically. Postoperatively, none of the patients developed infection,
      delayed wound healing, myelo-suppression attributed to adriamycin, and 74% of the
      patients were able to walk outdoors.

PMID- 9266035
TI  - Shear and tensile strength of hydroxyapatite coating under loading conditions. An
      experimental study in dogs.
AB  - The shear and tensile strength of a hydroxyapatite (HA) coating on a femoral
      component was studied after physiological loading conditions in 8 German
      Shepherds. A proximal macrostructure on the stem was used to protect this region
      from shear stresses. Another four implantations with uncoated components were
      used as controls. In vitro testing of the HA layer demonstrated excellent tensile
      strength and stability to surface deformation. The loaded implants were tested at
      6, 12, and 24 weeks. At 6 weeks the HA-coated components could easily be removed
      by axial loading, whereas the HA layer remained undamaged on the metal. However,
      pull out tests of implants older than 12 weeks showed complete debonding of the
      HA layer from the non-macrostructured surface due to shear forces in all cases.
      Debonding of the HA layer was also observed with microradiography. The
      macrostructured surface prevented dislodging of the component from this area at
      pull out test by distributing shear forces. Unlike in uncoated implants,
      considerable amounts of bone remained attached onto the HA macrostructure when
      the surrounding femur was pulled out. Shear forces cause debonding of the HA
      layer, while tensile stress affects failure within the bone. Physiological
      loading partially produces gaps at the interface so direct transmission of
      tensile forces onto the bone is lost, and the coating-metal interface becomes the
      weak point in the system.

PMID- 9266036
TI  - Management of trans-scaphoid perilunate dislocations. Herbert screw fixation,
      ligamentous repair and early wrist mobilization.
AB  - A retrospective review of 28 patients with 29 trans-scaphoid perilunate
      dislocations who underwent open reduction and Herbert screw fixation is
      presented. The majority of the patients had satisfactory results at 24 months of
      follow-up. A significantly better range of wrist motion was obtained in
      postoperative patients treated with cast immobilization for 4 weeks compared with
      those treated for longer than 5 weeks. The scaphoid fractures united well, with
      proper alignment of the carpal bones, regardless of the length of cast
      immobilization. We recommend open reduction, internal scaphoid fixation using a
      Herbert screw, carpal ligament repair and early cast removal in the management of
      trans-scaphoid perilunate dislocations.

PMID- 9266037
TI  - Do we underestimate the predictive value of the ulnar styloid affection in Colles
      fractures?
AB  - Various radiographic factors have been suggested as predictively important when
      dealing with an unstable distal radius fracture. Accordingly, many classification
      systems have been established in order to give an accurate description of a
      fracture and to grade the seriousness of the injury. In this paper, we use the
      classification of Colles fractures introduced by Frykman to investigate the
      predictive value of a concomitant fracture of the ulnar styloid. We found styloid
      affection to be a better predictor of a poor outcome than intra-articularity, but
      the combination carries the worst prognosis. We therefore suggest that a fracture
      of the distal radius associated with those two types of injuries should be
      considered for surgical treatment.

PMID- 9266038
TI  - Increased incidence of arthrosis in women could be related to femoral and pelvic
      shape.
AB  - In this study various femoral and pelvic geometrical parameters important for hip
      joint contact stress were determined. The parameters were measured from standard
      anteroposterior radiographs of healthy adult subjects and analysed by using
      descriptive statistical procedures. Women proved to have a significantly smaller
      femoral head radius and larger distance between the inner acetabular rims than
      men, both features which lead to an increase of contact stress in the hip joint
      articular surface. Since too high, long-lasting contact stress is unfavourable
      regarding the development of arthrosis, we propose that these differences in the
      femoral and pelvic geometry could be one of the reasons for the increased
      incidence of arthrosis in women.

PMID- 9266039
TI  - Does a single device prevent further slipping of the epiphysis in children with
      slipped capital femoral epiphysis?
AB  - All 170 patients (212 hips) treated between 1946 and 1992 for slipped capital
      femoral epiphysis (SCFE) with fixation in situ with a single device were reviewed
      to evaluate the incidence of further slipping of the epiphysis after primary
      treatment. In 154 hips, a smooth device without anchorage in the epiphysis was
      used and in 58, a device anchored in the epiphysis. In 3 hips, further slipping
      of the epiphysis occurred after primary treatment with no obvious cause. In 10
      hips, an obvious cause for further slipping of the epiphysis was found. These 10
      hips were re-operated due to the loss of epiphyseal grip in 6 hips,
      unsatisfactory placement of the device in 1, while in the remaining 3 hips, the
      device was removed before physeal closure. Twenty-six hips (12.3%) were re
      operated because the device had lost its epiphyseal grip before physeal closure,
      and in 25 of these hips the device was smooth and had no anchorage in the
      epiphysis. The conclusion of this study is that a single device with anchorage in
      the epiphysis is stable enough to prevent further slipping of the epiphysis in
      hips with SCFE.

PMID- 9266040
TI  - Fixation of osteotomies of the distal femur with absorbable, self-reinforced,
      poly-L-lactide plates. An experimental study on rabbits.
AB  - Osteotomies of the distal femur were fixed with two self-reinforced poly-L-lactic
      acid (SR-PLLA) plates and metallic screws placed through the plates on each side
      of the femur in 23 adult rabbits. They were followed-up after 3, 6, 12 and 24
      weeks. After killing, radiological, histological, microradiographic and
      oxytetracycline fluorescence studies were performed. Except for one
      histologically confirmed fibrotic non-union at 24 weeks, the osteotomies healed,
      including one involving a rabbit which had suffered an ipsilateral femoral shaft
      fracture of unknown cause. No malformations were observed, and the
      macroscopically detected swelling was a normal postoperative reaction. This study
      showed that SR-PLLA plates implanted on both sides on the bone are suitable for
      the fixation of weight-bearing cancellous bone osteotomies in rabbits.

PMID- 9266041
TI  - Sonography and MRI of experimental muscle injuries.
AB  - After sonographical examination with a 7.5-MHz linear array scanner, we created
      an experimental muscle injury of known site and location on 28 New Zealand white
      rabbits by stabbing them with a scalpel in the supraspinatus muscle. The changes
      in the healing process were followed and documented by sonography and magnetic
      resonance imaging (MRI) before and 2, 5, 11, 14, 36 and 64 days after injury. The
      changes in sonography and MRI followed a regular course. Ultrasound revealed an
      echo-poor area after injury with ever increasing echogenicity from the 14th day.
      Strong reflexes were found after 2 months. MRI showed few changes, only a slight
      increase of signal intensity, but a characteristic curve of calculated T2-times
      (a program of the MRI software). The interpretation of the sonographical picture
      in histopathological terms remained limited. The development of a hematoma and of
      fibrous scars can be followed up by sonography, but it is not possible to
      determine the point of time after injury very accurately. Nevertheless,
      sonography is a method of great value in the diagnosis of muscle injuries and,
      given certain limits, in the follow-up of the healing process, too. The
      significance of MRI can be increased by calculations with the implemented
      software, as in our study calculated T2-times produced a characteristic curve
      reflecting the shift of fluids after muscle injury.

PMID- 9266042
TI  - Chondropathia patellae.
AB  - The articular surface of the patella and the contiguous articular surfaces of the
      femoral condyles are sometimes affected by disintegrational changes of the
      articular cartilage, which remain localized there for a longer period of time. In
      consideration of the pronounced functional impairment arising at marked changes
      of these articular surfaces, resection of the patellar surface, metallic
      resurfacing of the patella, periosteal resurfacing of the patella, or
      patellectomy have been described as treatment by various authors. Most of these
      modalities were followed by shortcomings of the results, as indicated in
      pertinent follow-up examinations and reports. Thus, a more physiological modality
      of treatment, organic resurfacing of the patella with synovial tissue, was
      applied in 7 patients and led to satisfactory results as ascertained by long-term
      follow-up examinations.

PMID- 9266043
TI  - Surgical treatment of neuropathic scoliosis: morphologic and functional outcome.
AB  - We evaluated the morphologic and functional outcome as well as the extent of
      satisfaction following surgical treatment in 41 patients with progressive
      neuropathic scoliosis. The mean follow-up time was 5.6 years (range 2.5-20
      years), and follow-up rate was 97.6%. Posterior spine fusion was performed with
      new instrumentation techniques (Luque/Luque-Galveston, CD, ISOLA) in 29 patients,
      with extension onto the sacrum in 16 patients, and Harrington instrumentation in
      12. In 20 patients we did an additional intervertebral disc excision and fusion.
      Mean correction of the thoracic spine deformity, as assessed by comparing the
      Cobb angles on pre- and postoperative X-rays, was 53%, and of the lumbar spine
      55.2%, in patients classified as Lonstein I. Scolioses classified as Lonstein II
      evidenced an average correction of 46.2%. Functional improvement according to the
      Rancho-Los Amigos scheme could be demonstrated in 20 patients. Seventeen patients
      remained unchanged, whereas 4 patients showed deterioration. Cosmetic results
      were rated as excellent by 25 patients, good by 7, and poor by 1. For 8 patients
      the appearance was unimportant. Pain relief was experienced in all cases (n = 4)
      of the preoperative low-back or abdominal pain. The major complications were deep
      wound infection in 3 patients which led to revision surgery, and removal of
      instrumentation in 1 patient.

PMID- 9266044
TI  - Physiotherapy: an overestimated factor in after-treatment of fractures in the
      distal radius?
AB  - Supervision by physiotherapists, starting 4-6 weeks after cast removal, was
      compared with self-training in 110 patients treated for Colles' fracture. The
      patients guided by physiotherapists were all satisfied with the treatment, but no
      functional advantages could be discerned when compared with self-training.

PMID- 9266045
TI  - Proximal osteotomy in hallux valgus, long-term results of 167 operated feet. A
      retrospective study.
AB  - A total of 167 feet in 125 patients were treated with a proximal osteotomy of the
      first metatarsal for hallux valgus. In addition, in 115 feet a resection of the
      base of the proximal phalanx was conducted, and in 25 feet the head of some
      lesser metatarsal bone was resected. Eight years (range 5-10 years)
      postoperatively the patients were sent a questionnaire concerning the present
      state of their feet. In all, 105 patients (142 feet) replied, and 63% stated that
      they felt no pain in their feet at all. Indeed, 86% of the patients indicated
      that, everything considered, the operation was worthwhile. The most common
      complaint was the difficulty of finding shoes to fit; 22.5% of the patients
      stated that they had a hard time with this. The average preoperative
      metatarsophalangeal angle was 38 degrees, reduced by 22 degrees postoperatively.
      The average preoperative first intermetatarsal angle was 15 degrees, reduced by 5
      degrees after the operation. In the statistical analysis, no correlation between
      the preoperative body mass index, the hallux angle, the first intermetatarsal
      angle, the reduction achieved in the above mentioned angles by the operation, and
      patient satisfaction was found.

PMID- 9266047
TI  - Influence of a high hip center on abductor muscle function.
AB  - In 20 anatomic specimens with an acetabular defect (type Paprosky 3b), an
      acetabular component was implanted in the position of a high hip center. The
      vertical migration of the hip center ranged between 13 and 35 mm. It was
      accompanied by a lateralization and ventral migration of between 5 and 25 mm. The
      influence on the different abductor muscles was calculated through computer model
      comparing muscle force and muscle length before and after implantation of a high
      hip center. The increase in length of the gluteus maximus muscle and the
      posterior part of the gluteus minimus muscle ranged between 1% and 6%, while all
      other evaluated abductor muscles were shortened from 3% to 16%. The effect of the
      simultaneous changes of the lever arms was an increase in necessary muscle
      strength for pelvic stabilization from 140% to 250% compared with the original
      estimated strength prior to implantation. This may lead to insufficiency of the
      abductor muscles after placement of a high hip center. On the basis of these
      findings, we do not recommend the implantation of an acetabular component in the
      position of a high hip center.

PMID- 9266046
TI  - Results of the surgical treatment of calcaneo-navicular coalito.
AB  - We present the results after surgical treatment in 15 patients who suffered from
      calcaneo-navicular coalitio. A total of 20 operations were performed on 19 feet
      (3 T-arthrodesis, 5 simple resections, 9 resections with fat interposition, 3
      resections with muscle interposition). At the time of follow-up, the patients
      were examined clinically and radiologically. In addition, different functional
      tests were performed (heel-tip test, balance test, single-leg high jump, single
      leg jumping course). Ten of 17 patients who underwent radiographic study at the
      follow-up had a successful result. Patients who had a coalitio showed a tibial
      rotation (heel-tip test) of 11.5 degrees, and those patients without a coalitio
      had a tibia rotation of 20.3 degrees. Concerning the functional outcome, 12 of 17
      patients had a successful result. The range of motion of the subtalar joint did
      not correlate with the functional capacity of the ankle. Seven of 20 patients
      subjectively judged the outcome as a failure. The worst results were found in
      patients with pre-existing degenerative changes at the time of resection.

PMID- 9266048
TI  - Compression plating of tibial fractures following primary external fixation.
AB  - During the time period from May 1990 to December 1992, a total of 75 tibia
      fractures were treated in the Department of Traumatology at the University of
      Bonn. Thirty-eight patients with 40 tibial fractures were managed according to a
      regimen including primary stabilization, usually using external fixation, soft
      tissue reconstruction and delayed open reduction and internal fixation using an
      AO compression plate. The majority of the patients had been involved in motor
      vehicle accidents, leading to multiple injuries in 24 instances. An open fracture
      was seen 18 times. The 20% complication rate is comparable to the reports
      following intramedullary stabilization. Only one infection, following a grade 2
      open fracture, was seen after the definitive stabilization. Bony union was
      achieved after 15.7 weeks. In light of the complications associated with
      intramedullary nailing, such as fat or air embolism, heterotopic ossification and
      non- or malunions, use of the tibial plate does not offer just logistic
      advantages, but is a viable alternative for delayed stabilization of tibial
      fractures. No benefits in any form have been received or will be received from a
      commercial party related directly or indirectly to the subject of this article.
      No funds were received in support of this study.

PMID- 9266050
TI  - Tibial tubercle osteotomy in revision total knee arthroplasty.
AB  - In revision total knee arthroplasty, osteotomy of the tibial tubercle provided
      satisfactory exposure to extract the broken tibial metal tray with rigidly fixed
      stem easily and safely. Three patients (three knees) underwent this osteotomy and
      were followed for a minimum of 2 years (range 2 years and 2 months to 2 years and
      8 months). All of the osteotomies had healed within 6 months postoperatively.
      There were no complications related to the surgical technique.

PMID- 9266049
TI  - In vivo properties of an intramedullary hydroxyapatite plug to improve femoral
      stem fixation.
AB  - An intramedullary hydroxyapatite (HA) plug was inserted in each tibia of five
      rabbits. Histological observation showed the presence of newly formed bone tissue
      bridging between the inner cortex and the HA plug at 3 months postoperatively.
      This new bone was in direct contact with the HA plug, and there was no fibrous
      tissue intervention. Based on these results, the HA plug was used in a hip
      hemiarthroplasty with bone cement. The radiograph taken 4 years postoperatively
      showed that the plug-bone interface was indistinct, and some of the plug's edges
      became rounded by replacement with newly developed bone. The femoral component
      was stable without subsidence. The HA plug stabilized by bone ingrowth in the
      femoral canal would certainly be useful to prevent the femoral component from
      subsiding, in addition to increasing the cement-bone interface pressure at the
      time of surgery.

PMID- 9266051
TI  - Vascularized fibular grafts for the reconstruction of segmental tibial bone
      defects.
AB  - Free vascularized fibular grafts were employed in seven patients with large
      tibial defects following trauma or resection of tumour. All patients were
      followed for more than 5 years. Tibial union and excellent functional results
      were achieved in all seven patients. Free vascularized fibular transfer seems to
      be an effective method of treatment for massive segmental bone defects.

PMID- 9266052
TI  - Repair of neglected Achilles tendon ruptures: procedures and functional results.
AB  - Surgical repair of neglected Achilles tendon ruptures presents the challenge of
      restoring the function of the Achilles tendon complex while repairing the large
      defect that is created by the delay in appropriate treatment. We present our
      preferred technique for delayed repair and the results of six patients who were
      available for complete follow-up evaluation. The combined surgical technique
      includes: V-to-Y gastrocnemius recession or advancement, excision of the
      fibroadipose defect, end-to-end anastomosis, gastrocnemius aponeurotic flap to
      reinforce the anastomosis. Each of six patients were interviewed and examined
      clinically and by Cybex II isokinetic strength testing. All six patients have
      been able to return to their pre-injury activities. Cybex II isokinetic strength
      testing demonstrated peak torque deficiencies in plantar flexion ranging from
      2.5%-22% as compared with the unaffected limb. The overall results of the
      technique described indicate that very satisfactory functioning of a neglected
      Achilles tendon rupture can be obtained.

PMID- 9266053
TI  - Hallux valgus in young patients: long-term results after McBride operation.
AB  - The development of symptomatic hallux valgus deformities at an early age is
      rather uncommon and usually treated non-operatively. However, if surgical
      treatment is indicated, only so-called physiological procedures, especially e.g.
      McBride's soft-tissue realignment, should be considered. From 1970 to 1990, 11
      patients aged 12-20 years underwent McBride's procedure, giving a total of 21
      feet. For 9 of these patients (17 feet), the average follow-up was 14 years and
      consisted of patient's history, radiographs and physical examination. All in all,
      the outcome was judged as good in 10 of 17 feet, satisfying in 2 of 17 feet and
      dissatisfying in 5 of 17 feet by both patients and surgeon. This conspicuous
      variation in success rate will be discussed by means of two examples.

PMID- 9266054
TI  - Role of surgical treatment in 70 patients with vertebral metastasis causing cord
      or root compression.
AB  - Spinal metastasis plays an important role in the survival rate and general
      condition of cancer patients. In this paper, we present 70 patients with
      metastatic spinal tumors, diagnosed and surgically treated in the Departments of
      Neurosurgery and Orthopedics of Ankara Numune State Hospital between 1984 and
      1993. Our clinical observations suggest that the survival rate is influenced by
      the type of the primary lesion, pathology, and the patient's preoperative
      physical and neurological status.

PMID- 9266055
TI  - The "learning curve" of total hip arthroplasty.
AB  - Total hip arthroplasty (THA) is one of the major breakthroughs in modern
      orthopedics this century. Since its introduction in the early 1960s by Sir J.
      Charnley, it has become the most common form of arthroplasty. The art of
      performing THA has developed to a large extent, yet with the inevitable "price"
      of a learning curve. The rates of early and late complications reported in the
      orthopedic literature have been decreasing gradually, along with improved short-
      and long-term results. We report the results of two similar series of THA
      performed with an interval of 15 to 20 years, which show that the improvement of
      the results that form the learning curve of THA at our institution is
      statistically significant.

PMID- 9266056
TI  - Fresh osteochondral allografts at the knee joint: good functional results in a
      follow-up study of more than 15 years.
AB  - The treatment of deep chondral defects at the knee joint poses major difficulties
      and challenges to the orthopaedic surgeon, particularly in young patients for
      whom solutions like total or hemi-joint arthroplasty are not recommended, because
      of their limited durability. Biological resurfacing with materials such as
      perichondrium, periosteal allografts, and cultured chondrocytes is still at the
      experimental stage and there has been limited clinical validation. Since 1978, we
      have successfully used fresh osteochondral ('shell') allografts for the treatment
      of selected patients with a chondral defect at the knee joint. These grafts,
      implanted mainly in young patients, have proved durable and have provided good
      functional results for more than 15 years, as shown by an average of 84.6 in the
      Hospital for Special Surgery (HSS) Knee Score. The operative technique and
      results of long-term follow-up of patients receiving fresh, osteochondral
      ('shell') allografts are presented and discussed.

PMID- 9266057
TI  - Congenital extension contracture of metacarpophalangeal joints.
AB  - We report a case of congenital extension contracture of the fifth
      metacarpophalangeal joints in a 15-year-old boy who had no associated anomalies
      and was successfully treated by surgery. Congenital extension contracture of
      bilateral metacarpophalangeal joints has not been reported previously, and the
      entity can be considered to be a new subgroup of distal arthrogryposis with
      congenital distal limb contracture.

PMID- 9266058
TI  - Acute popliteal artery occlusion after total knee arthroplasty.
AB  - We describe the case of a 71-year-old man with calcium pyrophosphate dihydrate
      crystal deposition disease who developed acute popliteal artery occlusion
      immediately after total knee arthroplasty. Reperfusion was achieved thanks to the
      early diagnosis and thrombolytic therapy with urokinase. Arterial occlusion
      occurring after total knee arthroplasty is a rare but serious complication.
      Detailed preoperative evaluation of the peripheral arterial circulation and an
      early diagnosis seem to be important.

PMID- 9266059
TI  - Joint salvaging surgery for an extensive giant cell tumor of the proximal femur
      complicated by a transcervical fracture.
AB  - The case of a 20-year-old man with an unusually large giant-cell tumor of the
      proximal right femur complicated by a transcervical fracture is presented. In
      view of the patient's age, stabilization with a dynamic hip screw combined with
      valgus osteotomy, curettage and bone grafting was preferred to total hip
      replacement. Femoral head salvage has been successful to date.

PMID- 9266060
TI  - Paradoxical motion in spondylolisthesis due to two-segment instability.
AB  - We report here a paradoxical motion in unstable spondylolytic spondylolisthesis:
      a more forward displacement of the L5 vertebral body on the sacrum on the
      standing extension view than on the standing flexion view. An axial loading
      through the inferior articular process of the posteriorly displaced L4 on
      extension appears to be the cause, while the instability in the two contiguous
      segments may be an important contributing factor.

PMID- 9266061
TI  - Parosteal osteosarcoma of the tarsus.
AB  - Parosteal osteosarcoma is a very rare bone tumor with a predilection for the
      posterior aspect of the distal femoral metaphysis. A case of parosteal
      osteosarcoma of the tarsus of a 23-year-old woman is reported. This is the second
      case of parosteal osteosarcoma of the tarsus reported in the English literature.

PMID- 9266062
TI  - Intraosseous schwannoma of T12 with burst fracture of L1.
AB  - Intraosseous schwannoma of T12 with burst L1 fracture is extremely rare. Here we
      present a report of the successful treatment and 18-month follow-up of a 46-year
      old man with this complication.

PMID- 9266063
TI  - Necrotizing skin lesions induced by low-molecular-weight heparin after total knee
      arthroplasty.
AB  - We report the unusual complication of focal necrotizing skin lesions accompanied
      by moderate thrombocytopenia in a female patient undergoing thromboprophylaxis
      with low-molecular-weight heparin after total knee arthroplasty. Heparin-induced
      thrombocytopenia was suspected and confirmed using the heparin-induced platelet
      activation assay. The skin lesions improved gradually after the discontinuation
      of heparin application. In addition to the description of this exceptionally rare
      adverse effect of low-molecular-weight heparin, a brief discussion of previously
      reported cases is provided.

PMID- 9266064
TI  - In situ RT-PCR using fluorescence-labeled primers.

PMID- 9266065
TI  - Purification and cloning of differential display products.

PMID- 9266066
TI  - PCR synthesis of cDNA from total RNA.

PMID- 9266067
TI  - Pitfalls of PCR: cross-reactivity with joyride E. coli nucleic acid.

PMID- 9266069
TI  - PCR-based multiplex method for rapid screening of recombinant bacteria.

PMID- 9266068
TI  - Rapid cloning of PCR-derived RAPD probes.

PMID- 9266070
TI  - Direct sequencing of PCR-amplified 23S rDNA.

PMID- 9266071
TI  - Method to reverse the order of multiple cloning sites.

PMID- 9266072
TI  - Immediate digestion of fish muscle following field collections yields DNA
      suitable for RAPD fingerprinting.

PMID- 9266073
TI  - Isolation of DNA suitable for PCR for field and laboratory work.

PMID- 9266074
TI  - Use of a dental amalgamator to extract RNA from the gram-positive bacterium
      Streptococcus agalactiae.

PMID- 9266075
TI  - Quality control of centrifugal elutriation for studies of cell cycle regulations.

PMID- 9266076
TI  - Nonselective URA3 colony-color assay in yeast ade1 or ade2 mutants.

PMID- 9266077
TI  - Rapid generation of DNA probes by amplification of tandem repeats.

PMID- 9266078
TI  - Pyrophosphate in the binding reaction increases the sensitivity of mobility shift
      analysis.

PMID- 9266079
TI  - Re-probing of immunoblots after storage for more than a decade.

PMID- 9266080
TI  - Universal template plasmid for introduction of the triple-HA epitope sequence
      into cloned genes.

PMID- 9266081
TI  - Photoactivation of caged compounds in single living cells: an application to the
      study of cell locomotion.
AB  - Caged compounds are molecules whose biological function is masked until UV light
      induces a photo-chemical reaction that converts the molecules into a biologically
      active state. These probes provide very powerful tools in cell biology research,
      since the activation can be precisely controlled temporally and spatially by
      limiting their exposure to light. This report describes a simple caged compound
      illuminator that can be attached to an inverted microscope; it can simultaneously
      provide both sufficient UV illumination for photoactivation and epifluorescence
      excitation to monitor indicator fluorescence. As an example, we show that the
      cytoplasmic calcium level can be raised very rapidly by the photoactivation of a
      new caged compound, caged calcium ionophore DMNPE-A23187, and that this [Ca2+]i
      increase is associated with tail retraction of motile keratocytes.

PMID- 9266082
TI  - Automated differential display using a fluorescently labeled universal primer.
AB  - We have modified the automated differential display reverse transcription
      polymerase chain reaction technique (DDRT-PCR) such that a single fluorescently
      labeled universal primer (d(F)CTCACG-GATCCGTCGATTTT) is used in all PCRs together
      with a selection of arbitrary primers. We term this fluorescent detection
      procedure FDDRT-PCR. Anchoring primers of general structure dTGGTCTCACGGATCCTCGA
      (T)12 VN (where N can be any deoxynucleoside and V can be any deoxynucleoside
      other than thymidine) are used for the RT step, and the universal primer together
      with selected arbitrary primers are then used for the PCR amplification.
      Advantages of this approach are: (i) the fluorescently labeled universal primer
      is a constant feature in every PCR, so that changes in banding profile are highly
      likely to reflect the incorporation of different arbitrary 10-mer primers; (ii)
      artifacts that result from arbitrary 10-mer to arbitrary 10-mer primer
      amplifications are not observed by fluoresence detection on an automated gene
      scanner because such products are not fluorescently labeled; (iii) sample
      throughput and ease of data handling are increased when compared with the
      conventional radioactive/manual approach and (iv) using a single fluorescently
      labeled primer in all PCRs is highly cost-effective.

PMID- 9266083
TI  - Use of internal controls to increase quantitative capabilities of the
      ribonuclease protection assay.
AB  - Through the use of two internal controls, we have developed an improved method of
      quantitating ribonuclease protection assay (RPA) results. A truncated sense RNA
      fragment and an antisense RNA fragment for the gene of interest were transcribed
      from PCR fragments containing T7 bacterial promoters. An 18S ribosomal RNA
      fragment was also used. When radiolabeled antisense and 18S probes, along with
      sense fragment and sample RNA, were hybridized, digested with RNase A/T1 and gel
      electrophoresed, three distinct bands resulted. The antisense RNA fragment bound
      to the sense RNA fragment confirmed the integrity of the reaction. The antisense
      RNA fragment bound to endogenous mRNA measured the amount of specific gene
      expression in the sample. The 18S RNA fragment bound to endogenous mRNA
      determined the actual amount of sample added to the gel. Using the specific
      activities of the antisense and 18S transcripts, and scintillation counts of the
      protected fragments, we calculated the amounts of message and total RNA on the
      gel, determining picogram of message per microgram of total RNA. Final results
      were not based on assumed original amounts of RNA placed in the assay nor were
      they biased by lane-to-lane variations. Through the described adaptations, we
      have developed a well-controlled RPA that accurately and reproducibly quantifies
      gene expression.

PMID- 9266084
TI  - Increased informativeness of RAPD analysis by detection of microsatellite motifs.
AB  - The recently developed random-amplified microsatellite polymorphism (RAMPO)
      technique detects second-level amplification products that are useful as
      molecular markers. In the first step of the procedure, genomic DNA is amplified
      with a single arbitrary or microsatellite-complementary primer. PCR products are
      then electrophoretically separated, photographed, blotted and hybridized to a 32P
      labeled microsatellite probe. Autoradiography reveals highly reproducible,
      polymorphic, probe-dependent fingerprints, which are different from the ethidium
      bromide staining patterns. In this paper, we report the successful application of
      various mono-, tri- and tetranucleotide repeat motifs as RAMPO probes. We also
      compare the efficiency of arbitrary vs. microsatellite primers for the generation
      of RAMPO patterns. Repeated rehybridization to different probes has expanded the
      information contained in a single random-amplified polymorphic DNA (RAPD) gel at
      least fivefold. Pattern complexity varies with the length and sequence of the
      probe. Application of the technique to a genetic relatedness study in the genus
      Dioscorea (yam) yielded highly informative markers, mainly at an interspecific
      level.

PMID- 9266085
TI  - Efficient cloning method that selects the recombinant clones.
AB  - Directional cloning using cohesive ends is the most efficient cloning method.
      However, sometimes it is necessary to use blunt ends to clone a DNA fragment into
      the plasmid vector. Compared with that of cohesive ends, efficiency of blunt-end
      ligation is low. Compared with the native blunt ends (e.g., SmaI or EcoRV), blunt
      end ligation is particularly difficult when blunt ends are derived from
      overhangs. This results in low efficiency of insertion and high background from
      self-ligation of the vector. To remedy the problem, we developed a "positive
      selector" cloning strategy that provides positive selection for the recombinant
      clones. It is particularly useful when making complex recombinant constructs and
      the choice of restriction sites is limited.

PMID- 9266086
TI  - Identification of endonuclease activity in HIV-1 gp120 preparations produced
      using baculovirus expression systems.
AB  - Experiments undertaken with commercially available recombinantly produced human
      immunodeficiency virus Type 1 (HIV-1) gp120 demonstrated that the resuspended
      lyophilized protein, a product of the baculovirus expression system, had
      intrinsic nuclease activity. This nuclease activity was distinguishable from the
      molecular-grade bovine serum albumin that it was constituted in. The activity was
      thermolabile in that if the preparation was heated to 100 degrees C for 10 min,
      the activity was abolished, although this did not happen when it was stored at 
      20 degrees C. The nuclease activity was also Ca+2- and Mg+2-dependent, and had
      endonuclease as opposed to exonuclease activity. Zn+2 ions were found to inhibit
      the enzyme. The intensity of nuclease activity varied from batch to batch. A
      lyophilized homogenate of Sf9 insect cells expressing the Rho baculovirus-derived
      red blood cell protein 4.2 (Pallidin) was also found to have nuclease activity on
      reconstitution. In contrast, most, though not all E. coli-produced recombinant
      proteins were found to be free of nuclease activity. The use of activity gels to
      identify the size of the nuclease contained in the gp120 preparation was limited,
      because despite the use of many renaturation methods, the enzyme in the gp120
      preparation could not be functionally resuscitated following sodium dodecyl
      sulfate polyacrylamide gel electrophoresis. Immunoprecipitation studies were
      useful to demonstrate that nuclease activity in the gp120 preparation was
      functionally distinguishable from the gp120 itself. When mononuclear cells
      transformed with anti-CD3 were concurrently incubated with gp120 (5-40
      micrograms/mL), internucleosomal DNA fragments characteristic of apoptosis were
      demonstrated in the supernatant by DNA gel electrophoresis. In the context of HIV
      1 and AIDS, where the depletion of CD4+ T-cells has been found to be associated
      with apoptosis, nuclease activity intrinsic to the gp120 preparation used in
      experimentation may potentially alter experimental results.

PMID- 9266087
TI  - Long-range and highly sensitive DNase I footprinting by an automated infrared DNA
      sequencer.
AB  - We have shown that an automated DNA sequencer is applicable to fluorescence-based
      detection of fragments in DNase I footprinting. We demonstrated the potential of
      long-range and highly sensitive DNase I footprinting taking advantage of an
      infrared-fluorescence automated DNA sequencer. Footprints of human transcription
      factor SpI were reproducibly detected ranging approximately between 100 and 750
      bp on both strands of an 895-bp DNA fragment in a single electrophoresis run. We
      developed techniques in data collection and subsequent image processing for
      highly sensitive detection. Less than 0.1 footprinting unit (fpu: approximately
      4.5 ng) of SpI was detected using 3.1 fmol of a 512-bp DNA fragment. This is
      greater than 10-fold increase in sensitivity over what has previously been
      reported by visible dye fluorescence DNA sequencers. This method will be very
      important in systematic analysis of transcription regulatory regions and in large
      scale analysis of the transcription process.

PMID- 9266088
TI  - Generation of large libraries of random mutants in Bacillus subtilis by PCR-based
      plasmid multimerization.
AB  - We describe a PCR-based method for the generation of plasmid multimers that can
      be directly transformed into Bacillus subtilis with very high efficiency. This
      technique is particularly useful for the generation of large libraries of
      randomly mutagenized genes, which are required for the optimization of enzymes by
      directed evolution. We subjected the gene coding for the protease subtilisin to
      six consecutive rounds of PCR at three different levels of mutagenicity. The
      resulting 18 populations were cloned using our PCR multimerization protocol, and
      the mutation frequencies were determined by DNA sequencing. The resulting data
      demonstrate that the mutation frequency during PCR can be controlled by adding
      varying concentrations of manganese chloride to the reaction mixture. We observed
      a bias in the type of base pair changes with A and T being mutated much more
      frequently than C and G. We determined the fraction of active clones in all
      populations and found that its natural logarithm is proportional to the average
      mutation frequency of the populations. These data reveal that a fraction of about
      0.27 of all possible mutations leads to the inactivation of the subtilisin gene,
      which provides a measure for its structural plasticity.

PMID- 9266089
TI  - Automated cycle sequencing with Taquenase: protocols for internal labeling, dye
      primer and "doublex" simultaneous sequencing.
AB  - This paper describes automated cycle sequencing protocols for internal labeling,
      dye primer and "doublex" simultaneous sequencing using Taquenase, a new
      genetically modified DNA polymerase with increased thermostability. Sequencing
      performance both with labeled and unlabeled primer yields uniform unambiguous
      signals up to the resolution limit of the sequencing gels. Primer walking with
      internal labeling was successfully performed on Pl-derived artificial chromosome
      (PAC) constructs with 130-kb inserts. Taquenase, a commercially available
      modified thermostable sequencing enzyme (delta 280, F667Y Taq DNA polymerase),
      incorporates a variety of fluorescent dNTPs carrying fluorescein isothiocyanate,
      TexasRed or Cy5 labels during the cycle-sequencing process with higher efficiency
      than other thermostable DNA polymerases. Comparison to other modified Taq DNA
      polymerases suggests that the particular N-terminal deletion of Taquenase rather
      than the presence of the F667Y mutation is responsible for the efficient
      incorporation and extension of labeled dNTPs. Taquenase makes feasible highly
      accurate "doublex" simultaneous cylce sequencing on both strands of template DNA
      with two internal labels or two dye-labeled primers in combination with the EMBL
      2-dye DNA sequencing system, ARAKIS, or with two commercial DNA sequencers. It
      allows up to 2000 bases at > 99% accuracy to be determined in a single reaction.

PMID- 9266090
TI  - Self-seal reagent: evaporation control for molecular histology procedures without
      chambers, clips or fingernail polish.
AB  - Sensitive nucleic acid based detection methods such as in situ PCR, in situ RT
      PCR and PRINS have great potential in the areas of developmental biology,
      pathogenesis and diagnostics. However, control of evaporation from in situ
      reactions is critical to ensure reliable data. Self-Seal Reagent, a component
      added directly to the in situ reaction mixture, effectively controls evaporation
      during in situ procedures by creating an evaporation-limiting barrier around the
      periphery of a standard cover glass as the reaction proceeds. At the end of the
      procedure, the cover glass is easily removed by soaking in an aqueous solution. A
      model is presented for how Self-Seal Reagent controls evaporation while
      maintaining reagent concentrations. Self-Seal Reagent is shown to be effective in
      the detection of HIV sequences in cells by in situ PCR.

PMID- 9266091
TI  - Practical considerations in acquiring biological signals from confocal
      microscope. II. Laser-induced rise of fluorescence and effect of agonist droplet
      application.
AB  - Confocal laser scanning microscopy (CLSM) is extensively used in the study of
      cellular activities through monitoring the temporal and spatial changes of
      biologically active molecules such as cAMP and Ca2+ which have been rendered
      visible by fluorescent labels. During our work with fluo-3 and Ca2+, we noticed
      two potential sources of artifacts which can make interpretation of the
      experimental observations difficult. Firstly, the excitation laser light
      generates heat that enhances the conversion of residual non-fluorescent
      acetoxymethyl (AM)-esterified indicator to the fluorescent form, thus giving rise
      to erroneous signals. Secondly, addition of reagents onto the coverslips alters
      the position of the focal plane, again causing error. In this paper, we present
      the phenomena and suggest ways to control and eliminate false images.

PMID- 9266092
TI  - Activation of a NADH dehydrogenase in the human erythrocyte by beta-adrenergic
      agonists: possible involvement of a G protein in enzyme activation.
AB  - NADH dehydrogenase in the plasma membrane transfers electrons from NADH to
      external oxidants like ferricyanide, through pathways which are linked to
      metabolic processes in the cell. Hormone binding to specific sites (receptors)
      can modify the enzyme activity, suggesting a direct or indirect coupling between
      the redox system and the hormone receptors. Reduction of external ferricyanide to
      ferrocyanide by human erythrocytes was stimulated by beta-adrenergic agonists
      (adrenaline, ritodrine and isoxsuprine), this effect being dependent upon
      concentration and pH. The agonist-stimulatory effect was attenuated in the
      presence of metoprolol (10(-4) M), a beta-adrenergic antagonist, and was not
      modified in the presence of prazosin, an alpha-adrenergic antagonist, suggesting
      that modification of the redox activity is mediated by binding of the agonists to
      beta-adrenergic receptors present in the human erythrocytes. Basal and agonist
      dependent activities were inhibited in the presence of sulfhydryl reagents p
      chloromercuribenzoate (PCMB, 10(-5) M) and N-ethylmaleimide (NEM, 10(-3) M),
      indicating the involvement of -SH groups. Inactivation by NEM was reversed by
      washing the cells with GTP (10(-3) M) and GTP gamma S (10(-4) M), suggesting that
      the specific alkylated -SH group(s) is located on a G protein in the hormone
      receptor-G-protein complex. The human erythrocytes contain G proteins, displaying
      both guanine-nucleotide-binding properties and GTPase activity. Fluoride (10(-2)
      M) and fluoroaluminate (AlF4- (F-, 10(-2) M + Al3+, 10(-5) M), G protein
      activators, enhanced the basal and agonist-dependent activities, suggesting the
      involvement of G proteins in this system. The overall results indicated that one
      of the coupling components between the hormonal receptors and the redox system is
      probably a G protein, and the mechanism of enzyme activation after hormone
      binding to the receptor is based on the redox state of cysteine residues probably
      within the receptor-G-protein complex.

PMID- 9266093
TI  - Effect of exposure to continuous light and melatonin on ovarian follicular
      kinetics in the skipper frog, Rana cyanophlyctis.
AB  - Ovarian follicular kinetics and gravimetric changes in the ovary and oviducts
      were studied in the skipper frog, Rana cyanophlyctis, following exposure to
      continuous light and melatonin treatment during the breeding season. Daily late
      afternoon injections of melatonin (15 micrograms subcutaneous) for 30 days
      decreased the gonadosomatic index (GSI), whereas continuously available melatonin
      from subcutaneous implants did not influence the GSI compared to those of
      controls. Exposure to continuous light for 30 days stimulated the GSI, and
      melatonin given as daily injections prevented the continuous-light induced
      increase in GSI. Oviductal weights decreased only in the melatonin-injected
      groups. Data on follicular kinetics revealed a decrease in first-growth-phase
      (FGP) oocytes and an increase in medium-sized second-growth-phase (MSGP) and
      large-sized second-growth-phase (LSGP) oocytes following continuous-light
      exposure. Melatonin administered to continuous-light-exposed frogs did not change
      the FGP oocyte number; however, it reduced both the MSGP and LSGP oocytes.
      Melatonin administration to frogs held in a light and dark cycle increased FGP
      oocytes and decreased MSGP and LSGP oocytes. Atretic follicles increased in all
      melatonin-treated groups. The results suggest that continuous light stimulates
      and melatonin inhibits reproductive function in this species.

PMID- 9266095
TI  - Influences of light-dark shifting on the immune system, tumor growth and life
      span of rats, mice and fruit flies as well as on the counteraction of melatonin.
AB  - Animal models were designed to study the changes in immune function, oncogenicity
      and life span of rats, mice and fruit flies following light-dark (LD) shift
      manipulations. Alternating the photoperiod of LD 14:10 and DL 10:14 every 3 days
      in rats disrupted the circadian immune rhythm pattern, decreased the blood
      leukocyte concentration by 48% and lowered the percentage of lymphocytes in the
      blood from 71% (control) to 49.2%. In mice, the phagocytosis of neutrophils was
      only reduced by 7%, but the level of serum hemolysin dropped significantly in the
      photoperiod-shifted group as compared with animals kept under a constant
      photoperiod of LD 12:12 or LD 14:10. In Ehrlich-carcinoma- or sarcoma-180
      injected mice, a reduction of survival duration, acceleration of tumor growth and
      depression of the immune system were recorded in the LD-shifted animals. In
      addition, the life span of fruit flies was shortened by 9.6% by photoperiodic
      shifting. Melatonin treatment evidently counteracted the deleterious influences
      of photoperiodic shifting in the above animals. It is suggested that repeated
      inversion of the LD cycle results in a chronobiological abnormality that, in
      turn, induces dysfunctions. Reentrainment by exogenous melatonin may inhibit the
      harmful influences of photoperiodic shifting.

PMID- 9266094
TI  - Guanosine 5'-O-(3-thiotriphosphate) and cations regulate melatonin receptors, and
      melatonin inhibits cyclic AMP production in the spinal cord.
AB  - Effects of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) and cations on 2
      [125I]iodomelatonin binding were investigated in membrane preparations of the
      chicken spinal cord. At concentrations of 10 and 50 mumol/l, GTP gamma S dose
      dependently increased (p < 0.05) the equilibrium dissociation constant (Kd) and
      depressed (p < 0.05) the maximum number of binding sites (Bmax). Na+ at a
      concentration of 125 mmol/l significantly increased (p < 0.05) the Kd and
      decreased (p < 0.05) the Bmax, and Mg2+ (2.5 mmol/l) significantly increased (p <
      0.05) the Bmax without changes in Kd. In addition, Na+ and Mg2+ affected the
      interactions of GTP gamma S with melatonin receptors. In the spinal cord
      explants, melatonin (10 nmol/l) attenuated forskolin-stimulated cyclic AMP
      production by 53.1%, and preincubation with pertussis toxin abolished this effect
      of melatonin. These results suggest that the melatonin receptors in the chicken
      spinal cord are linked to its second messenger via a pertussis-toxin-sensitive
      guanine-nucleotide-binding protein, and that cations modulate these receptors.
      Our studies further support a previous hypothesis that melatonin exerts a direct
      action on spinal cord functions.

PMID- 9266096
TI  - Administration of melatonin and related indoles prevents exercise-induced
      cellular oxidative changes in rats.
AB  - In an attempt to define the role of the pineal hormone melatonin and two
      analogues (5-methoxytryptamine, 5MT, and 6-hydroxymelatonin, 6HM) in limiting
      oxidative stress, the present study investigated the changes in glutathione,
      lipid peroxidation, and the activity of the antioxidant enzyme glutathione
      peroxidase after exercise (swimming for 60 min) with or without treatment with
      the indolamines mentioned. Lipid peroxidation was measured by estimating tissue
      levels of malondialdehyde and 4-hydroxyalkenals; the experimental animals in
      these studies were male Sprague-Dawley rats. In the liver, swimming exercise
      increased the levels of reduced glutathione (GSH) and also significantly
      increasing oxidized glutathione (GSSG), while decreasing the GSH/GSSG ratio, an
      index directly related to oxidative stress. When the animals were treated with
      melatonin, the concentrations of GSH and GSSG were also increased after swimming;
      however, no reduction in the GSH/GSSG ratio appeared. In the animals treated with
      6HM the changes were the same as in those treated with melatonin. In muscle as
      well, the concentration of GSH and the GSH/GSSG ratio were decreased following 60
      min of swimming. Pretreatment of the rats with melatonin prevented these effects.
      Pretreatment of the rats with both 5MT and 6HM also prevented the changes. Brain
      GSH/GSSG ratio was not affected by either exercise or indolamine administration.
      Swimming enhanced lipid peroxidation in the liver, muscle and brain; however,
      this was prevented in animals treated with melatonin or 6HM before swimming.
      Glutathione peroxidase was significantly elevated after exercise in the brain but
      not in the liver and muscle. It is concluded that swimming imposes a severe
      oxidative stress and suggests that melatonin and, to a lesser degree, 5MT and 6HM
      confer protection against the oxidative damage associated with swimming for 60
      min. This mechanism may be reasonably attributed to their indole structure, which
      possibly allows these molecules to act as free-radical scavengers.

PMID- 9266097
TI  - Changes of biological features in breast cancer cells determined by primary
      chemotherapy.
AB  - BACKGROUND: To evaluate the changes in the biological features of breast cancer
      cells induced by primary chemotherapy (PCT) and their possible relationship with
      the response to therapy we performed an extensive immunohistochemical study
      before and after PCT. PATIENTS AND METHODS: PCT was administered to 29 women with
      breast cancer. On specimens obtained by tru-cut and post-chemotherapy surgery we
      analyzed the following parameters: histology, histologic grade, apoptotic index,
      hormone receptor levels, Ki67, PCNA, EGFr, bcl-2, p53, p170. The significance of
      the changes induced by PCT and their correlations with the type of response were
      evaluated. RESULTS: Twelve patients achieved a partial response with PCT. No
      baseline biological parameter correlated with the type of response. After PCT we
      observed a significant increase in the apoptotic index (p = 0.000), PCNA (p =
      0.036), EGFr (p = 0.005), and p170 expression (p = 0.001), regardless of the type
      of chemotherapy administered (anthracyclines, 25 cases, or CMF, 4 cases).
      Responder patients displayed a significant decrease in ER levels (p = 0.015),
      whereas in non responders there was an increase in PCNA (p = 0.008) and EGFr
      expression (p = 0.002). The apoptotic index and p170 expression rose after PCT
      regardless of the type of response. CONCLUSIONS: PCT induced significant
      variations in the phenotype of breast cancer cells. These changes might reflect
      the selection of new neoplastic clones with different biological properties and
      so could facilitate the choice of appropriate chemotherapy agents.

PMID- 9266098
TI  - Breast conserving therapy in stage I & II breast cancer in Korea.
AB  - A randomized clinical study of 187 patients with T1, T2 breast cancer was
      performed, in order to compare the effects of modified radical mastectomy (MRM)
      and breast conserving therapy (BCT) on breast recurrence, overall survival, and
      disease-free survival. One hundred eighty seven patients with T1, T2 breast
      cancer, admitted at Yongdong Severance Hospital from April 1991 to August 1994,
      were randomized into two different treatment groups. Of the 187 patients, 111
      patients had received MRM and 76 had received BCT. In any of the variables
      considered with the exceptions of age and menopausal status, patient
      characteristics such as tumor size, incidence of axillary lymph node metastasis,
      histologic grading, and estrogen and progesterone receptor positive rate were not
      significantly different between the two groups (p < 0.05). Using the Kaplan-Meier
      Product-limit method and log-rank test, the difference of locoregional
      recurrence, and overall and disease-free survival, between these comparable
      groups was analyzed. Average follow-up period was 37.6 months. Two out of 111 MRM
      patients and two out of 76 BCT patients had locoregional recurrence. Only one
      patient who had MRM was found to have a recurrence in her opposite breast. The
      overall survival rates in MRM and BCT patients were, respectively 93.7% and
      94.1%. Furthermore, the disease-free survival rates were, respectively, 89.2% and
      93.9%. This result indicates that there were no significant differences between
      two groups in locoregional recurrence, and overall and disease-free survival.
      Having gained a better cosmetic appearance, the conservative treatment group was
      satisfied with the BCT. In this study, we conclude that BCT is a good alternative
      surgical treatment modality for T1, T2 Korean breast cancer patients, which could
      substitute for the more traditional MRM. However, further follow-up will be
      needed for long-term results.

PMID- 9266099
TI  - An individual patient-based meta-analysis of tamoxifen versus ovarian ablation as
      first line endocrine therapy for premenopausal women with metastatic breast
      cancer.
AB  - We performed a meta-analysis of randomized trials comparing tamoxifen to ovarian
      ablation carried out either by surgery or irradiation as first-line hormonal
      therapy for pre-menopausal women with metastatic breast cancer. Patients in all
      trials included were required to have measurable disease and to be currently
      menstruating or within 1 year of cessation of menses, and to have estrogen
      receptor (ER) positive or unknown disease (ER negative women were admitted to one
      of the studies). Individual patient data were obtained from the four studies
      identified and the results updated to June 1992. A total of 220 eligible patients
      were enrolled in the four trials. There was no difference in overall response
      rate between tamoxifen and oophorectomy across the four trials (p = 0.94, Mantel
      Haenszel test). The odds reduction for progression was 14% +/- 12% and for
      mortality 6% +/- 13% in favour of tamoxifen, results which were not statistically
      significant (p = 0.32 and 0.72, respectively). Although the design of all four
      studies included a cross-over to the other therapy, only 54/111 patients
      receiving ovarian ablation and 34/109 patients receiving tamoxifen as primary
      therapy actually crossed over to the other arm at the time of disease
      progression. Response to initial treatment with tamoxifen was predictive of
      subsequent response to ovarian ablation (p < 0.05), and response to initial
      therapy with ovarian ablation was predictive of subsequent response to tamoxifen
      (p < 0.05). Support curves based on log-likelihood ratios revealed that this meta
      analysis provides moderate evidence rejecting a 14% advantage for ovarian
      ablation compared to tamoxifen in terms of odds of disease progression. A 25%
      advantage for ovarian ablation with respect to odds of death is also rejected
      with moderate evidence. We conclude that the efficacy of tamoxifen appears to be
      similar to that of ovarian ablation by surgery or irradiation as first-line
      therapy for premenopausal, ER positive metastatic breast cancer, and is unlikely
      to be substantially inferior.

PMID- 9266100
TI  - A randomized crossover trial of tamoxifen versus ovarian ablation for metastatic
      breast cancer in premenopausal women: a report of the National Cancer Institute
      of Canada Clinical Trials Group (NCIC CTG) trial MA.1.
AB  - We concluded a randomized crossover trial comparing tamoxifen 40 mg daily with
      ovarian ablation for treatment of metastatic breast cancer in premenopausal
      women. Objective responses (complete response (CR) plus partial response (PR))
      were observed in 5/20 patients treated initially with tamoxifen and in 3/19
      patients initially treated with ovarian ablation (p = 0.69). Seven additional
      patients were stable (SD) on tamoxifen while five additional patients were stable
      after ovarian ablation, for CR + PR + SD rates of 12/20 (60%) for tamoxifen and
      8/19 (42%) for ovarian ablation (p = 0.34). Median time to disease progression
      was 184 days for tamoxifen and 126 days for ovarian ablation (p = 0.40, logrank
      test, odds ratio for progression 0.71). Overall survival times were also similar:
      a median of 2.35 years for tamoxifen and 2.46 years for ovarian ablation (p =
      0.98, logrank test, odds ratio for death 1.07). Side effects from tamoxifen
      included hot flashes and menstrual abnormalities. With one exception, these
      toxicities were not sufficient to require dose reduction. In this small study,
      tamoxifen was associated with similar response rates, response durations, and
      survival times to those observed with ovarian ablation.

PMID- 9266101
TI  - Captopril modulates hormone receptor concentration and inhibits proliferation of
      human mammary ductal carcinoma cells in culture.
AB  - The present study evaluated the effect of the angiotensin converting enzyme (ACE)
      inhibitor captopril on estrogen (ER) and progesterone (PR) receptor concentration
      and on proliferation in two lines of human mammary ductal carcinoma cells in
      culture: T-47D (ER+/PR+) and Hs578T (ER-/PR-). The incorporation of
      [3H]thymidine, validated by cell count, served as an index of proliferation.
      Compared to control cells, T-47D cells incubated for 48 hrs in 1, 2, or 5 mM
      captopril (but not in 0.5 mM) exhibited a reduction in ER from 130 +/- 6 to 32 +/
      32 fmol/mg cytosolic protein, and an increase in PR from 1780 +/- 120 to 2740 +/
      400 fmol/ mg protein (p < 0.05). Western analysis confirmed these drug-induced
      changes in the concentration of immunoreactive receptor proteins. Captopril also
      induced the appearance of low but detectable PR in the Hs578T cells at
      concentrations as low as 50 microM. Captopril inhibited the incorporation of
      [3H]thymidine by both cell types during a 48 hr incubation, although Hs578T cells
      were 2-3 times more resistant than were T-47D cells. This cytostatic effect of
      captopril was not due to cytotoxicity as indicated by 51Cr release, and was not
      accompanied by significant changes in cell cycle distribution as determined by
      flow cytometry. The incorporation of [3H]uridine (RNA synthesis) and [14C]alanine
      (protein synthesis) also were inhibited by captopril, suggesting a general
      antimetabolic effect of the drug in the ductal carcinoma cells. These are novel
      actions of a common antihypertensive agent. In contrast, the nonthiol ACE
      inhibitor lisinopril, and penicillamine, a thiol compound with virtually no ACE
      inhibitory activity, had no effect on any of these endpoints.

PMID- 9266102
TI  - Risk factors for breast cancer: a case-control study of screen-detected breast
      cancer in Miyagi Prefecture, Japan.
AB  - We examined the associations between reproductive factors and the risk of breast
      cancer on the basis of information from a total of 201,363 breast cancer
      screening program participants in Miyagi Prefecture, Japan, during 1987-1991. A
      case-control study method was applied on analysis. Data on 204 breast cancer
      cases identified and 810 screening year-, age- and screening area-matched normal
      controls were extracted. After adjustment for potential confounders, a trend of
      decreasing risk of breast cancer with increasing number of parity was observed (p
      for trend = 0.03). Among parous women, lactation for the last child decreased the
      risk of breast cancer (odds ratio (OR) = 0.61, 95% confidence interval (95% CI)
      0.39-0.94). These findings were consistent with those in clinical breast cancer
      reported previously. When cases were divided into two age groups, younger (< or =
      49 y.o.) and older (50 y.o. < or =), family history of breast cancer among mother
      and sisters (OR = 3.51, 95% CI 1.05-11.80), and lactation for the last child (OR
      = 0.46, 95% CI 0.25-0.84) were associated with younger age breast cancer, whereas
      number of parity was associated with older age breast cancer (p for trend =
      0.03). The results by age group suggest that different mechanisms may exist in
      breast cancer developing at early and late onsets.

PMID- 9266103
TI  - Associations of alcohol, height, and reproductive factors with serum hormone
      concentrations in postmenopausal Japanese women. Steroid hormones in Japanese
      postmenopausal women.
AB  - We measured serum levels of estradiol (E2), sex hormone-binding globulin SHBG),
      progesterone, and dehydroepiandrosterone sulfate (DHEAS) in 61 postmenopausal
      women drawn from female residents in a community in Japan to evaluate the
      relationships between these hormone levels and potential breast cancer risk
      factors. The information on reproductive history, body size, alcohol use, and
      physical activity was obtained by means of a self-administered questionnaire.
      There was a significant trend in increasing E2 level with increasing height after
      taking account of age and body mass index (BMI) (p for trend = 0.04). BMI was
      inversely associated with SHBG level after controlling age (p for trend = 0.01).
      Decreasing progesterone with increasing BMI was observed after controlling age
      and history of hysterectomy (P = 0.05). Alcohol consumption was positively
      associated with E2 level and there was a strong linear trend after controlling
      for age, height, and BMI (p for trend = 0.001). Trend for increasing DHEAS with
      alcohol consumption was also statistically significant after controlling for age
      and history of hysterectomy (p for trend = 0.01). Reproductive factors as well as
      physical activity were not related to any of the hormone levels.

PMID- 9266104
TI  - Expression of the prolactin gene in normal and neoplastic human breast tissues
      and human mammary cell lines: promoter usage and alternative mRNA splicing.
AB  - Prolactin (PRL) has been implicated in the development of mammary cancer in
      rodents and humans. Although PRL and its mRNA have been detected in breast
      tissues and some mammary cell lines, the role of PRL as an autocrine/paracrine
      growth factor within the breast is not clear. A second, more distal, promoter has
      recently been identified in the human PRL gene. We have used reverse
      transcription-polymerase chain reaction (RT-PCR) to determine whether the distal
      or the proximal promoter directs expression of the PRL gene in normal and
      neoplastic breast tissues and in mammary cell lines. Total RNA was isolated from
      10 normal and 20 neoplastic breast tissue samples and from 8 mammary cell lines;
      MDA-MB-231, SK-BR-3, T-47D, MCF10, MCF10T2, and 3 MCF7 derivatives. The RNA was
      reverse transcribed to cDNA using random hexamers as primers. PCR amplification
      of the cDNAs was performed, using a variety of PRL-specific primer pairs, and the
      DNA products were subjected to agarose gel electrophoresis and Southern blotting.
      The resulting data indicate that the PRL gene is expressed in the majority of
      both normal and neoplastic breast tissue samples, as well as all of the mammary
      cell lines. PRL-specific PCR products corresponding to transcripts that
      originated from the distal promoter were observed in a subset of the normal and
      neoplastic breast tissue samples and mammary cell lines. Together these data
      indicate that PRL transcripts in human breast tissues and human mammary cell
      lines originate, at least in part, from the distal PRL promoter. In addition,
      data are presented which suggest that PRL transcripts in breast tissues and
      mammary cell lines may undergo alternative splicing.

PMID- 9266105
TI  - Five-day infusion fluorouracil plus vinorelbine i.v. in metastatic pretreated
      breast cancer patients.
AB  - The aim of the present study was to evaluate the clinical activity and side
      effects of a combination chemotherapy consisting of a five-day continuous
      infusion of fluorouracil and i.v. vinorelbine in metastatic previously treated
      breast cancer patients. The patient population was represented by 28 women with
      evaluable disease, previously subjected to chemotherapy, including anthracycline
      containing regimens in 89% of patients. Treatment consisted of five-day infusion
      of 700 mg/m2/day of fluorouracil and vinorelbine, 20 mg/m2 i.v. bolus on day 1
      and 6. In the absence of Grade > 3 leukopenia and stomatitis, cycles were
      repeated every three weeks, for a total of six cycles. Four complete and thirteen
      partial responses were documented, accounting for a response rate of 61% (95% CI:
      40.5-78.5); the clinical efficacy was high even in patients unresponsive to prior
      anthracycline treatment. The median response duration calculated from the first
      drug injection was 8 months (range 4-11). Treatment was well tolerated, with 4%
      Grade 4 stomatitis and 20% Grade 3 leukopenia as the main toxic reactions. This
      drug combination is active in metastatic previously treated breast cancer
      patients, is devoid of severe side effects, and warrants further testing.

PMID- 9266106
TI  - CD44 isoforms with exon v6 and metastasis of primary N0M0 breast carcinomas.
AB  - New isoforms of CD44 with alternatively spliced exons have recently been
      described. Expression of exon v6 seems to be of particular interest. It has
      indeed been associated with poorer outcome of breast cancer patients with node
      invasion at diagnosis. However, no data were available for patients N0M0 (with
      neither metastasis nor node invasion at diagnosis). Moreover, previous
      statistical analyses were realized using immunohistochemical methods to detect
      CD44v6 expression although several variants with exon v6 have been described. We
      investigated expression of isoforms containing CD44v6 using an RT-PCR approach
      and a panel of 25 normal breast specimens, 10 mammary fibroadenomas, 8 cystic
      samples and 52 primary breast tumors (38 invasive N0M0). Normal breasts,
      fibroadenomas, and cysts all express the same variant, A (with exon v6 only),
      while several transcripts are amplified in tumors. Expression of variants other
      than A correlates with acquisition of a malignant phenotype. Invasive cancers
      also express additional variants in comparison with in situ carcinomas.
      Metastasis capacities seem to be associated with transcription of variants other
      than A but also with no transcription of some of them, variants D (with exons v6
      and v10) and L (with exons v6 to v10). Expression of variants D and L correlates
      with higher percentages of disease-free survival and better outcome. Expression
      of CD44 splice variants with exon v6, as detected by RT-PCR, might be a useful
      prognostic factor for breast cancer. However, since the series size is small, our
      results need to be confirmed by later studies on a larger number of patients.

PMID- 9266107
TI  - Hepatic toxicity caused by adjuvant CMF/CNF in breast cancer patients and
      reversal by tamoxifen.
AB  - The purpose of the study was to determine the effect of adjuvant chemotherapy on
      liver enzymes in breast cancer patients. Furthermore, the effect of tamoxifen on
      liver enzymes was analyzed. Liver function tests from 194 breast cancer patients
      who received adjuvant chemotherapy with or without tamoxifen (TAM) were reviewed.
      Statistically very significant increases were seen in alkaline phosphatase,
      aspartate acetyl transferase, and gamma glutamyl transferase levels in these
      patients receiving adjuvant chemotherapy. No statistical changes were noticed in
      bilirubin levels. If tamoxifen was given together with adjuvant chemotherapy, no
      changes in liver function tests were detected. Hepatic toxicity was induced in
      breast cancer patients by adjuvant CMF/CNF therapy (cyclophosphamide,
      methotrexate, 5-fluorouracil, mitoxantrone). These changes were mostly mild.
      Adjuvant tamoxifen reduced the increase in liver enzymes caused by adjuvant
      chemotherapy.

PMID- 9266108
TI  - BRCA2 hereditary breast cancer pathophenotype.

PMID- 9266109
TI  - Beyond biases and outdated perceptions. HIV prevention and mentoring.

PMID- 9266110
TI  - Gatekeeping in primary-health care. Challenging a sacred myth.

PMID- 9266111
TI  - Long-term cognitive effects of drinking.

PMID- 9266112
TI  - Canadian Consensus Conference on the Assessment of Dementia reports.

PMID- 9266113
TI  - Sexism.

PMID- 9266114
TI  - Preventive education for physicians.

PMID- 9266115
TI  - Testing women for HIV.

PMID- 9266116
TI  - Ophthaproblem. Corneal rust ring.

PMID- 9266117
TI  - Dermacase. Unilateral laterothoracic exanthem.

PMID- 9266118
TI  - Radiology Rounds. Choroid plexus cysts.

PMID- 9266119
TI  - Practice tips. Mole no more.

PMID- 9266120
TI  - More evidence linking benzodiazepines and falls.

PMID- 9266121
TI  - How does hormone replacement therapy affect the longevity of women with different
      risk profiles?

PMID- 9266122
TI  - Do physicians discuss HIV testing during prenatal care?
AB  - OBJECTIVE: To determine the frequency with which Hamilton, Ont, general
      practitioners and family physicians discussed and offered HIV testing during
      prenatal care. DESIGN: Cross-sectional mailed survey. SETTING: Family physicians'
      and general practitioners' offices in Hamilton, including group or solo private
      practices and community health centres. PARTICIPANTS: General practitioners and
      family physicians in Hamilton identified from the Ontario Medical Association and
      the 1995 Canadian Medical Directory. Two hundred forty-one practitioners were
      sent surveys; 25% had moved or no longer practised family medicine, and 65% (140
      of 216) were returned. MAIN OUTCOME MEASURE: Frequency with which physicians
      discuss with and offer HIV testing to prenatal patients. RESULTS: Eighty percent
      of clinicians felt they understood their professional role in providing HIV
      testing, and more than 90% had referred female patients for HIV testing. Eight
      percent of physicians always discussed HIV when reviewing pregnancy care, and 5%
      always offered HIV testing to patients in the first trimester of pregnancy.
      CONCLUSIONS: Currently, few physicians discuss HIV testing with all their
      prenatal patients.

PMID- 9266123
TI  - Human immunodeficiency virus risk awareness. Evaluation of a CME program for
      family physicians.
AB  - OBJECTIVE: To determine whether a continuing medical education (CME) program on
      AIDS risk awareness would enhance physicians' knowledge of HIV and AIDS, their
      "intent-to-change" practice behaviour, and their ability to integrate their
      knowledge into hypothetical clinical scenarios; and to identify participant
      characteristics that affect their knowledge of risks and how they intend to
      behave regarding HIV testing. DESIGN: Before-and-after study using a
      questionnaire. SETTING: The city of Winnipeg and 16 rural communities in
      Manitoba. PARTICIPANTS: Convenience sample of physicians who attended the AIDS
      Risk Awareness Program and completed a questionnaire before the presentation (96
      of 142 eligible physicians). MAIN OUTCOME MEASURE: A two-point or greater change
      on a Likert scale in the desired direction for each questionnaire item. RESULTS:
      Physicians were classified as sensitized or less sensitized depending on previous
      experience with HIV-positive and AIDS patients. Less sensitized physicians
      significantly improved their scores in all three areas. Sensitized physicians and
      women physicians significantly improved their knowledge and reported more intent
      to ask patients routinely about HIV risk behaviours. Physicians' sex, age,
      religion, and years in practice had an effect on these improvements. CONCLUSIONS:
      The AIDS Risk Awareness Program was successful in improving physicians'
      knowledge, attitude to intent-to-change behaviour and ability to integrate
      knowledge into practice scenarios. Physicians with true learning needs benefited
      the most from the CME program.

PMID- 9266124
TI  - Identifying the need for curriculum change. When a rural training program needs
      reform.
AB  - OBJECTIVE: To identify what changes should be made in the University of British
      Columbia's rural family practice training program curriculum to help graduates be
      better prepared to practice. DESIGN: Two cross-sectional surveys via mailed
      questionnaires: one designed to measure physicians' self-reported preparedness
      for practice and the other to measure the importance of various rural family
      medicine components. SETTING: Rural training program graduates and preceptors
      representing rural communities in British Columbia. PARTICIPANTS: Thirty-nine
      graduates of the rural training program between 1982 and 1991 and 14 community
      based rural training program preceptors representing eight communities throughout
      the province participated in this study. MAIN OUTCOME MEASURES: Percentage of
      graduates of the rural program who reported themselves to be underprepared on
      each family practice item and preceptors' mean scores for the attributed
      importance to rural practice of each item on this questionnaire. RESULTS: A list
      of curriculum areas most in need of reform was created. This list included
      trauma, counseling skills, radiology, vacuum extraction, fracture care,
      exercising community leadership, cost-effective use of diagnostic tests, using
      community health resources, obtaining hospital privileges, ophthalmology,
      dermatology, otolaryngology, personal and professional growth, relationships with
      other physicians, and personnel issues. CONCLUSIONS: Using both the level of
      graduates' self-reported underpreparedness and the attributed importance of
      elements of rural practice, as indicated by the preceptor survey, we developed a
      list of the areas of the rural training program curriculum most in need of
      reform.

PMID- 9266126
TI  - Help! HIV information sources.

PMID- 9266125
TI  - Treatment options for benign prostatic hyperplasia.
AB  - OBJECTIVE: To examine current treatment options for benign prostatic hyperplasia
      with emphasis on randomized, clinical trials and our current management approach.
      QUALITY OF EVIDENCE: Benign prostatic hyperplasia remains difficult to define
      clinically or measure objectively. As a result, research has been fairly weak.
      With newer treatments, however, more definitive studies have been reported. MAIN
      FINDINGS: Transurethral resection of the prostate remains the criterion standard
      for severe disease. Watchful waiting, medical management, or early surgical
      intervention are all valid options for moderate disease and should be tailored to
      the characteristics and desires of individual patients. Recent minimally invasive
      surgical techniques, such as microwave and laser surgery, have not yet achieved
      the quality of evidence to be generally recommended. CONCLUSIONS: Management of
      benign prostatic hyperplasia should be individualized to patients' circumstances
      and personal choices.

PMID- 9266127
TI  - Our strength for tomorrow: valuing our children. Part 1: Consultations. Report of
      the CFPC's Task Force on Child Health.

PMID- 9266128
TI  - Joint destruction in rheumatoid arthritis: biological bases.
AB  - The pathogenesis of rheumatoid arthritis (RA) can be explained through two main
      hypotheses: macrophage-fibroblast and macrophage-T cell interactions. The
      interplay between the various populations is influenced by a strong genetic
      component, which determines the severity of the disease in some cohorts of
      patients attending referral centers. The key question of the nature of the
      antigen(s) driving joint inflammation still remains unsolved. Exogenous antigens
      such as viruses or bacteria have long been searched for in the synovial fluids as
      well as in tissues, but convincing evidence of their pathogenic role are lacking.
      Data have been accumulated on the possible role of autoantigens, such as the
      spliceosomes, filaggrin, calpastatin, type II collagens, or other endogenous
      peptides, but no definite role regarding their potential contribution to the
      activation of T cells has been established. Once the process starts, a
      progressive recruitment of inflammatory T cells and macrophages into the joints
      occurs through a complex series of adhesion and migratory events. The key driving
      steps leading to synovial inflammation and cartilage destruction, along with the
      potential contribution of some key molecules, have been described, thus opening
      possible perspectives for a therapeutic approach.

PMID- 9266129
TI  - Prognostic criteria in rheumatoid arthritis: can we predict which patients will
      require specific anti-rheumatoid treatment?
AB  - Longitudinal studies of rheumatoid arthritis (RA) have shown that joint damage
      often occurs early in the disease. Therefore, the early treatment of RA with
      "disease modifying" drugs is gaining acceptance. However, many patients
      presenting with inflammatory polyarthropathy will follow a benign course.
      Rheumatologists need to be able to target the use of potentially toxic drugs to
      those cases where the benefits clearly outweigh the risks. This approach requires
      reliable assessment of the prognosis at an early stage in the disease process. We
      have critically evaluated a large number of published studies which claim to
      provide clinically useful information regarding the prognosis of RA. CONCLUSION:
      The majority of studies have methodological flaws which limit their value. A
      small number of published studies exist which provide useful data about
      estimating the prognosis of RA. Currently evaluated prognostic indicators are
      only moderately successful and there is an urgent need for methodologically sound
      research in this area.

PMID- 9266130
TI  - Why randomized controlled clinical trials do not depict accurately long-term
      outcomes in rheumatoid arthritis: some explanations and suggestions for future
      studies.
AB  - The randomized controlled clinical trial is the "gold standard" to evaluate
      therapeutic interventions, but is more effectively applied to studies of the
      short-term treatment of acute diseases than to the long-term treatment of chronic
      diseases. Clinical observations often provide more accurate outcome data in
      rheumatoid arthritis (RA) than clinical trials. Limitations of clinical trials to
      depict long-term outcomes in RA include a relatively short observation period,
      patient selection resulting from exclusion criteria, inflexible dosage schedules
      and concomitant drug therapies, evidence that some markers of inflammatory
      activity are suboptimal surrogate indicators of long-term articular damage, the
      fact that statistically significant results are not necessarily clinically
      important, the influence of the design on the results-despite a control group,
      ignoring of individual variation in reporting results, the non-standardized
      interpretation of side effects which introduces bias, distortion of the "placebo
      effect", and lack of capacity to detect rare side effects. The clinical trial
      represents only an initial step in the evaluation of a therapy for a chronic
      disease. Awareness of these limitations should lead to the improved design of
      clinical trials and clinical studies to improve the long-term outcome for people
      with RA.

PMID- 9266131
TI  - The design of clinical trials aimed at assessing the DC-ART properties of new
      molecules in rheumatoid arthritis.
AB  - Considerations in designing clinical trials of novel molecules are not different
      from those that should be considered in every rheumatoid arthritis clinical
      trial. This article raises some critical issues that clinicians have to face in
      the planning and design of clinical trials for new molecules in rheumatoid
      arthritis. The most frequent problems are related to outcome measures (core set
      of endpoints, improvement and remission), patient populations, characteristics of
      the study design, and economic evaluation. Although some of these issues have
      been resolved by consensus, further research needs to be carried out to support
      the use of different measurement techniques. Because clinical trials remain the
      most powerful investigative instrument for deciding about the benefits of new
      advances in medical therapy, their design should be based on an appropriate
      methodology.

PMID- 9266132
TI  - Statistical considerations concerning clinical studies designed to assess DC
      ARTs.
AB  - The aim of this paper is to contribute to the current ongoing debate regarding
      how to optimise clinical research on rheumatoid arthritis. Bearing in mind the
      main difficulties represented by the particular characteristics of the disease
      and its treatment, as well as the limitations of some of the trials that have
      been carried out over the last thirty years, we discuss how some of the general
      statistical considerations regarding all clinical trials should be applied to
      those specifically designed to assess disease-controlling antirheumatic
      therapies.

PMID- 9266133
TI  - The radiological assessment of rheumatoid arthritis.
AB  - Antirheumatic therapy has changed from a rather conservative approach towards
      more aggressive early intervention. Objective measures of the course and outcome
      of rheumatoid arthritis are essential to understand the disease process and
      evaluate the therapeutic response. Radiological evaluation fulfils many of the
      criteria of objectivity: the films provide a permanent record and can be
      evaluated serially and repeatedly; the changes do not fluctuate with disease
      activity; and good technique and correct timing can keep the radiation load to a
      very acceptable level. Consequently, therapies can be evaluated on the basis of
      their efficacy on radiological progression. In clinical practice, a visual
      qualitative assessment is usually sufficient, but for therapeutic trials or
      studies of disease progression in certain patient groups, quantitative methods
      are needed. A number of different evaluation systems have been introduced, but
      none of these have gained universal acceptance. No ideal evaluation method (which
      should be rapid, easy to use and have a good level of reproducibility) has yet
      been found. Here we make provisional recommendations on the conduct of future
      therapeutic trials to maximise the likelihood that they will give conclusive
      results using radiographic outcome assessments.

PMID- 9266134
TI  - From disease modification to disease control in rheumatoid arthritis.
AB  - In the development of therapies to treat rheumatoid arthritis, measurement of
      response is essential. Such measurement has incrementally advanced from symptom
      modification through radiological improvement to a requirement for change in
      inflammation, change in function, and the prevention of further structural
      damage.

PMID- 9266136
TI  - Currently used second-line agents: do they control the disease course?
AB  - The treatment of rheumatoid arthritis patients with second-line agents (SLA) has
      changed in recent years. Patients are treated increasingly earlier since it has
      been shown that joint damage starts already in the first years of the disease. In
      addition, the number of effective SLAs available has increased, including drugs
      with a relatively fast mode of action and better drug survival curves. Short-term
      data indicate that effective SLA treatment can slow down radiographic
      progression. Recent studies have also shown that some SLA combinations are more
      effective than monotherapy.

PMID- 9266135
TI  - The treatment of rheumatoid arthritis in this century: from spas to monoclonal
      antibodies.
AB  - In this paper I review the advances in the treatment of rheumatoid arthritis that
      have taken place in this century. From spas to monoclonal antibodies for the
      manipulation of the immune system, we have come a long way in just one hundred
      years. However, although research is being pursued in many promising directions,
      the discovery of a truly effective treatment for rheumatoid arthritis is still
      being awaited.

PMID- 9266137
TI  - Adverse drug reactions of DMARDs and DC-ARTs in rheumatoid arthritis.
AB  - Comprehensive meta-analyses have revealed that survival on DMARD therapy in
      rheumatoid arthritis can be classified according to several factors: the number
      of adverse drug reactions, the percentage of drop-outs, and the duration of
      usage, which is clearly linked to both drug efficacy and drug toxicity. When
      taking into account of all of these issues, the impact of each DMARD can be
      scored differently, but certainly the length of time on a given DMARD gives us a
      conclusive, clinically important overview of its overall efficacy and safety. On
      these grounds, studies lasting two years or more have demonstrated that, while
      sulphasalazine can be employed for a median length of 12 months, methotrexate
      treatment can be maintained for more than 5 consecutive years. Severe and life
      threatening complications have been observed with all conventional DMARDs.

PMID- 9266138
TI  - Effects of cyclosporin on joint damage in rheumatoid arthritis. The Italian
      Rheumatologists Study Group on Rheumatoid Arthritis.
AB  - According to the most recent literature, few antirheumatic drugs can claim
      disease-controlling properties over the anatomical joint damage in rheumatoid
      arthritis (RA). A small number of studies have favored one or another of the
      available agents, in particular parenteral gold salts, sulphasalazine and
      methotrexate, but the evidence regarding their efficacy is not convincing when
      analysed using methodological criteria known to be important in evaluating
      radiologic evidence of joint damage. The radiologic results in long-standing RA
      patients have shown that CsA may be of benefit in reducing disease progression.
      Data from the second year of a clinical trial designed to compare the disease
      controlling, anti-rheumatic properties of CsA with those of conventional disease
      modifying anti-rheumatic drugs (DMARDs) in early RA support the hypothesis that
      CsA may be useful in delaying the appearance of new joint erosion.

PMID- 9266139
TI  - Rescue of DMARD failures by means of monoclonal antibodies or biological agents.
AB  - Over the past decade different monoclonal antibodies or other biological agents
      have been developed to complete the available therapeutic repertoire for treating
      RA patients. Thus, monoclonal antibodies to block the TNF-alpha or TNF-alpha
      receptor fusion proteins, respectively, have been successfully applied in the
      treatment of RA patients refractory to other treatment principles. In addition,
      using the IL-1 receptor antagonist, similar promising data have been obtained in
      placebo-controlled, double-blind trials. Initial attempts are presently being
      conducted to test combination therapies, using monoclonal antibodies directed
      against the proinflammatory cytokines and cell surface molecules, and long-acting
      rheumatic drugs such as methotrexate. Hopefully within the next few years newly
      developed biological agents will be available for use in daily clinical practice.

PMID- 9266140
TI  - Lipomatous medulloblastoma.
AB  - A case of cerebellar lipomatous medulloblastoma in a 55-year-old male subject,
      clinically presenting with signs of intracranial hemorrhage and cerebellar
      dysfunction, is described. Magnetic resonance imaging revealed an enhancing
      irregular vermian lesion invading the left cerebellar hemisphere. The patient
      underwent a craniotomy with total excision of tumor. Histologic examination
      revealed that a large portion of the tumor was composed of mature adipocytes.
      Lipoblasts with multiple vacuoles were not detected. Remaining tumor exhibited
      morphological, ultrastructural, and immunohistochemical features of
      medulloblastoma with both neuronal and glial differentiation. DNA analysis by
      flow cytometry revealed that the neoplasm was aneuploid. After 8 months, a new
      magnetic resonance imaging did not show any recurrence and the patient was free
      of symptoms. Morphological and immunohistochemical features, together with the
      age at the time of surgery and DNA content, suggest that lipomatous
      medulloblastoma is to be considered as a rare but distinct variant of
      medulloblastoma.

PMID- 9266141
TI  - Carotid artery dissection in a young adult: cystic medial necrosis associated
      with an increased elastase content.
AB  - A dissecting aneurysm of the right internal carotid artery was found in a 22-year
      old man, who rapidly became unconscious and hemiparetic after an accident
      occurring during sport. The dissection was limited to the intima and internal
      elastic lamina. Patterns of cystic medial necrosis with mucoid degeneration were
      present in the right internal carotid artery proximal to the site of dissection,
      in the thoracic aorta, and in several visceral arteries. In the region of the
      right internal carotid artery affected with cystic medial necrosis, calcification
      and also splitting of the internal elastic lamina was found. Such calcification
      was also present at the site of the dissection, at the tip of the ruptured and
      recoiled elastic lamina. These changes, dissection as well as cystic medial
      necrosis, were associated with an elevated elastase content, a decrease of desmin
      and an increase of vimentin expression. Ultrastructurally, in areas affected by
      cystic medial necrosis a corresponding transformation of medial smooth muscle
      cell phenotype from the contractile to the metabolic state was found. The
      topographical relation of dissecting aneurysm, cystic medial necrosis, and an
      increased elastase content is suggestive of a causal relation, and the
      possibility of common etiological factors is discussed.

PMID- 9266142
TI  - Kaposi's sarcoma in the cerebellum of a patient with AIDS.
AB  - A case of Kaposi's sarcoma in the left cerebellar hemisphere of a patient with
      AIDS is presented. The lesion was not detected with imaging techniques in the
      patient who, during the clinical course, did not show neurological signs and
      symptoms. This small nodular lesion was only revealed at autopsy. This rare
      finding is an example of the broad spectrum of central nervous system involvement
      in HIV-1-infected individuals.

PMID- 9266143
TI  - Cardiac myxoma with glandular elements metastatic to the brain 12 years after the
      removal of the original tumor.
AB  - This report describes a case of cardiac myxoma with glandular elements metastatic
      to the brain. The histological appearance of the brain tumor was characterized by
      irregularly shaped glands lined by a single layer of mucous-secreting cells. The
      glands rested on a stroma made of connective tissue with myxoid changes in which
      short cords of cells with eosinophilic cytoplasm were occasionally detected. The
      cardiac tumor was a myxoma in which only 2 small glandular structures were
      identified. Immunohistochemically, the gland-lining cells were positively stained
      by cytokeratin AE1-AE3, CAM 5.2, and B 72.3. CEA was detected as a thin layer on
      the luminal surface of the cells and in the cytoplasm of goblet cells. The myxoma
      cells in the stroma were not stained by cytokeratins. This is the first report of
      brain metastases from a cardiac myxoma made of glandular elements.

PMID- 9266144
TI  - Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS).
AB  - We report the clinical, pathological, and genetic findings of a case of MELAS
      syndrome. This was a man who died for metabolic failure at the age of 27 years.
      His familiar history was positive for hypoacusia and stroke. He was of short
      stature and presented mild mental retardation. Since the age of 21 he suffered
      from recurrent brain-ischemic lesions mainly in the occipital lobes, documented
      by repeated CT scans. The laboratory data and muscle biopsy disclosed lactic
      acidosis with ragged red fibres. Neurophysiological data and peripheral nerve
      biopsy showed an axonal neuropathy. A point mutation in the tRNALeu(UUR) gene of
      mitochondrial DNA was detected in 5 post-mortem tissues and in muscle biopsy. No
      defects of mitochondrial respiratory chain were detected. The histological and
      ultrastructural studies of the brain showed multiple and heterogeneous ischemic
      lesions with no obvious alterations of cerebral blood vessels. These lesions do
      not correspond to the vascular territories of main cerebral arteries. Our
      observations support the hypothesis that local metabolic alterations would play a
      crucial role in the pathogenesis of cerebral ischemic lesions in MELAS. The
      correlation between genetic, biochemical, and pathological data are discussed.

PMID- 9266145
TI  - Telangiectatic osteosarcoma of the skull. A post-Paget case.
AB  - We report a case of post-Paget telangiectatic osteosarcoma of the skull in a 75
      year-old woman. Such a neoplasia is a rare variant of osteosarcoma, a tumor rare
      in the cranic bones. The patient was submitted for a careful analysis by the
      following procedures: technetium scintigram, X-rays, CT scan, and MRI. After the
      surgical procedure, pathological examination confirmed the diagnosis. Both
      radiological and pathological pattern of this tumor are discussed in relation to
      the differential diagnosis. Our report shows that benign lesions may represent a
      possible cause of diagnostic errors. They must be excluded by histological
      analysis.

PMID- 9266146
TI  - Retrospective study on dengue fatal cases.
AB  - Immunohistochemical procedure (avidin biotin peroxidase complex) was applied in
      formalin-fixed and paraffin-embedded tissues obtained from 5 fatal cases of
      dengue infection associated with encephalopathy. Dengue virus antigen was
      demonstrated in the cytoplasm of phagocytic mononuclear cells from liver, spleen,
      and lung. Moreover, dengue viral antigens were here, to our knowledge, first
      demonstrated in the central nervous system (CNS) and numerous immunolabelled
      cells were found in brain sections from 3 cases. Extended immunohistochemical
      studies carried out in 1 case showed virus-positive cells mostly located within
      Virchow Robin space of medium size and small veins, infiltrating the white and
      grey matter, and often situated close to neurons displaying apparent cytopathic
      features. Furthermore, immunostaining for CD68 antigens demonstrated that most
      CD68+ macrophages and dengue antigen-positive cells share similar morphology and
      localization, suggesting a unique identity for at least part of these cells.
      Since in dengue fever, virus replicates mostly in cells of macrophage lineage,
      our results seem to indicate that infiltration of virus-infected macrophages
      could be one of the pathways by which viruses enter the brain in dengue
      encephalitis. Whether bone marrow-derived infected macrophages and viral-free
      particles induce CSN lesions through immune, metabolic, and/or direct viral
      induced mechanisms will be essential to better understand the pathogenesis and
      provide new therapeutic strategies for dengue-associated encephalitis. As the
      evidence of tissue damage was nonspecific, the detection of virus antigen by
      immunoperoxidase technique appeared to be highly reliable for dengue diagnosis.

PMID- 9266147
TI  - Cerebral amyloid angiopathy with extensive mineralization.
AB  - Cerebral amyloid angiopathy (CAA, congophilic angiopathy) occurs with aging,
      Alzheimer's disease, and certain rare familial syndromes. It is an important risk
      factor for spontaneous intracerebral hemorrhage. In addition to the accumulation
      of amyloid within the walls of cortical and leptomeningeal blood vessels, CAA is
      often accompanied by other vascular changes (CAA-associated vasculopathies, CAA
      AV). This case report describes the unusual finding of extensive vascular
      mineralization with CAA, a rare form of CAA-AV which was detected during life.

PMID- 9266148
TI  - Stiff-man syndrome: possible autoimmune etiology targeted against GABA-ergic
      cells.
AB  - We report the case of a female patient, who died at the age of 66 years. Besides
      an insulin-dependent diabetes mellitus (IDDM) she had developed the clinical
      symptoms of stiff-man-syndrome (SMS) and harbored autoantibodies against
      glutamate-decarboxylase (GAD) in blood and liquor. GAD catalyzes the biosynthesis
      of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). The autopsy
      revealed typical alterations observed in diabetes mellitus including an
      incomplete fibrosis of pancreatic Langerhans islets. A decrease of GABA-ergic
      cells in the cerebellar cortex was observed, and a size reduction of Renshaw
      cells in the spinal cord. Furthermore, a dilution series of a polyclonal GABA
      antibody delivered a reduced immunofluorescence in the cerebellum. In skeletal
      muscle a neurogenic atrophy was observed. As described in literature, the
      clinical symptoms decayed following clonazepam administration. We suggest that
      this case including GAD autoantibodies, dramatic loss of GAD-expressing
      pancreatic cells, and loss or atrophy of GABA secretory neurons, supports the
      hypothesis that SMS may be an autoimmune disease directed against GABA-ergic
      cells. Furthermore, we suggest a neuronal hypersensitivity at the spinal cord
      level caused by the atrophic Renshaw cells.

PMID- 9266149
TI  - Chromosome 17 allelic loss in astrocytic tumors and its clinico-pathologic
      implications.
AB  - To prognosticate the implications of various allelic losses on chromosome 17 in
      the morphology and biology of astrocytic tumors, we have examined loss of
      heterozygosity (LOH) at 14 microsatellite loci on chromosome 17 in a series of 19
      astrocytic tumors (3 astrocytomas, 5 anaplastic astrocytomas, and 11
      glioblastomas). The DNA samples extracted from tumor and matched normal brain
      tissue were amplified by polymerase chain reaction (PCR) followed by
      polyacrylamide gel electrophoresis and photography under UV transillumination.
      The molecular genetic data were compared with immunohistochemistry performed with
      antibodies to glial fibrillary acidic protein (GFAP), MIB-1 and p53 protein. LOH
      was observed in 11/19 (58%) instances with frequent involvement of TP53, NF1, and
      D17S795 loci, LOH at D17S578 and D17S520 occurred in recurrent tumors
      exclusively. Allelic status of D17S795 in all 12 informative instances were
      concordant with GFAP immunoreactivity (p < 0.01, Fisher's test). p53
      immunopositivity (> 25% of tumor cell nuclei) was seen in 11 (58%) tumors, of
      which 6 were informative of TP53 locus with 2 (33%) demonstrating LOH. The MIB-1
      staining indexes in astrocytomas, anaplastic astrocytomas, and glioblastomas were
      1.9 +/- 0.9, 8.4 +/- 4.0, and 17.1 +/- 7.1% (mean +/- SD), respectively, and
      their differences were statistically significant (p < 0.05, Student's t test). A
      trend of inverse relationship between patient survival and the number of tumor
      cell nuclei with immunohistochemically detectable p53 protein was seen in
      glioblastoma cases: 20.5 +/- 12.7 versus 13.7 +/- 6.3 months (mean +/- SD) in
      instances with > or > or = 25% positive cells, respectively. We conclude, the
      intriguing correlation between allelic status of D17S795 microsatellite locus and
      GFAP immunoreactivity suggests the possible involvement of q21.2 segment of
      chromosome 17 in the morphology and biology of astrocytic tumors.

PMID- 9266150
TI  - Familial dementia due to adult polyglucosan body disease.
AB  - BACKGROUND: Adult polyglucosan body disease (APBD) is a rare disorder, presenting
      with varying combinations and severity of upper and lower motor neuron
      dysfunction, sensory deficits, dementia, and urinary incontinence. Onset is in
      the 40s or 50s. The diagnosis is made by finding polyglucosan bodies (PB) in
      histologic sections of brain or spinal cord, peripheral nerve, or dermal sweat
      glands. Although 2 pairs of the 22 previously reported cases were siblings, the
      familial nature of the disease has not been emphasized. METHODS: We report 2
      adult siblings, a male and a female, each of whom had the clinical diagnosis of
      vascular dementia. Both were confirmed at autopsy to have APBD. We characterized
      the lesions in autopsy tissues using a battery of histological stains, lectin
      histochemistry, and electron microscopy. RESULTS: Innumerable PB were distributed
      throughout brain, heart, skeletal muscle, liver, and dermal sweat glands. PB were
      highlighted by periodic acid Schiff stain and concanavalin A lectin.
      Ultrastructurally, PB were composed of aggregates of filaments within axons and
      astrocytic processes, and lying free in the neuropil, but not within neuronal
      perikarya. CONCLUSIONS: It is important to consider APBD in cases of familial
      dementia of unknown etiology. Ante-mortem biopsy of axillary skin may be
      diagnostic.

PMID- 9266151
TI  - Degenerative ataxias: genetics, pathogenesis and animal models.
AB  - At present, seven inherited neurodegenerative disorders have been identified to
      be caused by the polyglutamine-coding CAG triplet expansions in the genes
      responsible. The long stretch of polyglutamines appears to play a key role in the
      pathogenesis. Disease models, just recently established with cultured cells and
      animals, will enable elucidation of common disease mechanisms and treatments.

PMID- 9266152
TI  - Of molecular interactions, mice and mechanisms: new insights into Huntington's
      disease.
AB  - Huntington's disease is caused by expansion of a CAG trinucleotide beyond 35
      repeats within the coding region of a novel gene. Recently, new insights into the
      relationship between CAG expansion in the HD gene and pathological mechanisms
      have emerged. These include a more precise understanding of the relationship
      between CAG repeat length and age of onset, progress in transgenic and
      excitotoxic animal models, identification of a novel huntington-interacting
      protein, and intriguing connections between huntington and the apoptotic
      machinery. We have combined many of these new findings into a model that suggests
      mechanisms and predicts outcomes by which the pathogenesis of Huntington's
      disease may be initiated. The development of appropriate in-vitro and animal
      models for Huntington's disease will allow the validity of this model to be
      tested.

PMID- 9266153
TI  - Apoptosis in neurodegenerative disorders.
AB  - We review here recent reports pertaining to the issue of apoptosis in
      neurodegenerative diseases. Tissue culture models, animal models and human
      pathological studies are discussed. At present, there is supportive, but not
      definitive, evidence for apoptosis in a number of neurodegenerative disorders.

PMID- 9266154
TI  - Neuropsychology and advances in memory function.
AB  - Recent developments in the functional and neural bases of several aspects of
      memory are described including long term cortical memory storage, the transition
      from immediate to permanent memory mediated by medial temporal structures,
      working memory, memory retrieval, and implicit memory. These are linked to
      current data on the nature of anterograde and retrograde amnesia in the
      degenerative diseases, and also to issues in the clinical diagnosis of memory
      impairments. Understanding the bases of memory can inform the diagnosis of memory
      impairments in degenerative diseases, and the patterns of impairment seen in the
      degenerative diseases can help contribute to knowledge of the mechanisms of
      normal memory.

PMID- 9266155
TI  - Advances in hereditary spastic paraplegia.
AB  - Hereditary spastic paraplegia refers to a group of clinically similar disorders
      whose primary feature is insidiously progressive lower extremity weakness and
      spasticity. Hereditary spastic paraplegia is genetically diverse: loci for
      autosomal recessive (chromosome 8p), autosomal dominant (chromosome 2p, 14q, and
      15q), and x-linked hereditary spastic paraplegia have been identified. The
      existence of hereditary spastic paraplegia families for whom the disorder is
      unlinked to these loci indicates the existence of additional, as yet
      undiscovered, hereditary spastic paraplegia loci. Hereditary spastic paraplegia
      exhibits axonal degeneration that is maximal at the terminal portions of the
      longest central nervous system axons. Efforts to positionally clone the
      hereditary spastic paraplegia gene are in progress.

PMID- 9266156
TI  - The HIV-1 associated dementia complex: a metabolic encephalopathy fueled by viral
      replication in mononuclear phagocytes.
AB  - HIV enters the brain soon after virus exposure but elicits profound neurological
      deficits in infected humans years later usually during progressive
      immunosuppression and the development of the acquired immune deficiency syndrome.
      The neurological disease complex associated with virus infection occurs in a
      large proportion of infected patients and is commonly referred to as HIV-1
      associated dementia complex. The neuropathogenesis of central nervous
      system/viral infection revolves around mononuclear phagocytes (brain
      macrophage/microglial) infection and immune activation in brain. Macrophages
      secrete neurotoxic factors that elicit neuronal injury and inevitably death
      leading to the constellation of cognitive and motor impairments common during
      progressive disease. Neurotoxic factor production requires virus entry and
      replication, the evolution/selection of neurovirulent HIV-1 strains and the
      production of viral and cellular immune factors injurious to human neurons.
      Interestingly, neurological deficits, the HIV-1 associated neuropathology and
      viral replication disease are not always associated. This has led to the notion
      that viral replication induces the autocrine/paracrine production of
      cellular/viral factors leading to a metabolic encephalopathy. Anti-retroviral and
      anti-inflammatory therapies should prove increasingly beneficial for treatment
      and, ultimately, reversal of HIV-1 associated dementia complex in the affected
      human host.

PMID- 9266157
TI  - Advances in imaging Parkinson's disease.
AB  - Positron emission tomography and single photon emission computed tomography both
      now provide an objective means of quantitating loss of striatal dopaminergic
      terminal function in Parkinson's disease and of following disease progression.
      18F-dopa positron emission tomography can also detect frontal changes in
      Parkinson's disease and preclinical disease in 30% of asymptomatic adult
      relatives of familial cases. Positron emission tomography, single photon emission
      computed tomography and proton magnetic resonance spectroscopy are all useful for
      distinguishing Parkinson's disease from atypical syndromes where diagnostic doubt
      exists.

PMID- 9266158
TI  - The role of pallidotomy in Parkinson's disease and dystonia.
AB  - Pallidotomy has been re-explored for the treatment of Parkinson's disease and is
      now being used for the treatment of medically intractable dystonia. Although
      initial results are favourable for both disorders, determination of the long term
      benefits will require well controlled clinical trials.

PMID- 9266159
TI  - Novel approaches to the symptomatic treatment of parkinsonian syndromes:
      alternatives and adjuncts to dopamine-replacement.
AB  - Advances in understanding basal ganglia function have suggested several
      nondopaminergic approaches to the treatment of parkinsonian symptoms. Data from
      studies in animal models of Parkinson's disease suggest that it is realistic to
      believe that these approaches might have antiparkinsonian efficacy comparable to
      those of currently available dopamine-replacing agents and might not be
      associated with debilitating dyskinetic side-effects after prolonged treatment.

PMID- 9266160
TI  - The clinical and pathologic hallmarks of progressive supranuclear palsy.
AB  - This article reviews recent studies evaluating the clinicopathologic markers of
      progressive supranuclear palsy, which have helped establish standardized clinical
      and pathologic diagnostic criteria. Although these criteria increase diagnostic
      accuracy, the clinical and pathologic overlap between progressive supranuclear
      palsy and other disorders remains. Factors that may contribute toward managing
      progressive supranuclear palsy patients better are discussed and the
      etiopathogenicity of the disorder is hypothesized.

PMID- 9266161
TI  - Movement disorders and mitochondrial dysfunction.
AB  - Primary defects of mitochondrial DNA leading to respiratory chain dysfunction
      have been described in association with dystonia, chorea and parkinsonism.
      Myoclonus remains the commonest movement disorder associated with such defects.
      The genetic basis of Leigh's syndrome, which is frequently associated with
      movement disorders, may be mitochondrial or nuclear. Respiratory chain
      dysfunction has been identified in Huntington's disease in addition to
      Parkinson's disease, but the cause and relationship of this dysfunction to the
      pathogenesis of these common disorders is not yet determined.

PMID- 9266163
TI  - Degenerative diseases.

PMID- 9266162
TI  - Idiopathic, myoclonic and Dopa-responsive dystonia.
AB  - The clinical manifestations and the present status of our knowledge of the
      genetics of the idiopathic, myoclonic and Dopa-responsive dystonias are reviewed.
      The relevance of recent genetic findings to the classification of the idiopathic
      dystonias and to the molecular pathogenesis of Dopa-responsive dystonia are
      emphasized.

PMID- 9266164
TI  - Movement disorders.

PMID- 9266165
TI  - Minimized proteins.
AB  - The design of bioactive small molecules for interaction at larger protein-protein
      interfaces remains a challenge. Recent progress towards minimizing proteins into
      significantly smaller polypeptides has been achieved via both rational design
      processes and selection from vast combinatorial libraries. Such 'mini-proteins'
      represent a potential intermediate step toward the development of drugs targeted
      to protein-protein interfaces.

PMID- 9266166
TI  - Scaffolds for engineering novel binding sites in proteins.
AB  - The combination of combinational protein chemistry and powerful selection
      techniques has resulted in the development of novel protein ligands based on the
      randomization of surface residues of a parental protein which is used as a
      scaffold. Such binding proteins, selected from libraries via specific binding
      towards a given target ligand, have the potential to replace natural antibodies
      in various biotechnological applications.

PMID- 9266167
TI  - 3D structural information as a guide to protein engineering using genetic
      selection.
AB  - A great variety of protein systems have been investigated in the past year using
      structure-guided evolutionary strategies. On the basis of available 3D structural
      information, critical regions of proteins have been targeted for randomizing
      mutagenesis and active variants of the corresponding genes have been selected.
      These approaches help characterize structural and mechanistic features of
      proteins and have important implications for design.

PMID- 9266168
TI  - Combinatorial protein design: strategies for screening protein libraries.
AB  - Powerful strategies for screening protein libraries further strengthen the
      arguments for applying 'irrational' approaches to understanding and designing new
      proteins. Developments during the past year include the application of functional
      complementation and automation to reduce screening loads, as well as the use of
      computerized data acquisition to characterize whole protein libraries rather than
      just selected individuals.

PMID- 9266169
TI  - Modeling transmembrane helical oligomers.
AB  - Recently, methods for the analysis and design of water-soluble, oligomeric
      bundles of alpha helices, including coiled coils, have reached a high level of
      sophistication. These same methods may now be applied to transmembrane helical
      bundles. Studies of the transmembrane domains of glycophorin, phospholamban, and
      the M2 protein from influenza A virus exemplify this general approach.

PMID- 9266170
TI  - Engineering metal-binding sites in proteins.
AB  - Metal-binding sites have been engineered into both de novo designed and naturally
      occurring proteins. Although the redesign of existing metal-binding sites in
      naturally occurring proteins still offers the most promise for a successful
      design, the more challenging goal of engineering metal-binding sites in de novo
      designed proteins and peptides is being achieved with increasing frequency.
      Creating new metal-binding sites in naturally occurring proteins combines the
      strength of both approaches. Currently, all three approaches are being used
      effectively in elucidating the structure and function of naturally occurring
      metalloproteins.

PMID- 9266171
TI  - Engineering peptides and proteins that undergo alpha-to-beta transitions.
AB  - In the 'protein-only' hypothesis, prion diseases are proposed to be the result of
      conformational changes of the normal form of the prion protein (PrPC) with a
      highly alpha-helical conformation to a pathogenic scrapie form (PrPSc) with a
      predominantly beta-sheet conformation. Recent studies examining the folding
      process of proteins, as well as the amyloidogenesis of peptides and proteins
      including prion proteins, Alzheimer's beta-peptides and other pathogenic protein
      mutants, have provided insight into the conformational changes essential to
      fibrillogenesis and correct folding.

PMID- 9266172
TI  - Molecular dynamics simulations of lipid bilayers.
AB  - During the past decade, computer simulations of bilayers have moved from the
      realm of model systems to realistic systems containing tens of phospholipids
      along with the requisite number of water molecules hydrating the entire molecular
      assembly. Concomitant with the ability to model larger and larger systems,
      simulators have also begun to utilize more accurate numerical tools to ensure
      that the temperature, pressure, simulation timescales, parameter sets and long
      range electrostatic interactions of bilayers are correctly accounted for in a
      typical molecular dynamics simulation. With these tools in hand, work has already
      begun to define the structure, function and dynamics of bilayer, bilayer/small
      molecule and bilayer/protein systems. Thus, we have reached an era in which
      simulators will tackle more and more detailed issues regarding complex bilayer
      systems.

PMID- 9266173
TI  - Small-scale lipid-membrane structure: simulation versus experiment.
AB  - Recently, it has become obvious that the conventional picture of the fluid lipid
      bilayer component of biological membranes being a fairly structureless 'fluid
      mosaic' solvent is far from correct. The lipid bilayer displays distinct static
      and dynamic structural organization on a small scale, for example in terms of
      differentiated lipid domains, and evidence is accumulating that these structures
      are of importance for the functioning of biological membranes, including the
      activity of membrane-bound enzymes and receptors and morphological changes at the
      cell surface. Insight into the relationship between this small-scale structure
      and biological functioning holds promise for a more rational approach to modulate
      function via manipulation of the lipid microenvironment and the lipid/protein
      interface in particular. Computer simulation has proved to be a useful tool in
      investigating membrane structure on a small scale-specifically the nanometer
      scale (1-100 nm), which is in between the molecular scale accessible by various
      spectroscopic techniques and molecular dynamics calculations, and the micrometer
      scale accessible by scattering and microscopy techniques.

PMID- 9266174
TI  - Lipid microdomains in cell surface membranes.
AB  - Lipid microdomains within cell membranes are detected by a variety of
      experimental techniques, each of which characterizes microdomains on a different
      time and spatial scale. The sum of the data on lipid microdomains has yet to be
      integrated into a single model of cell membrane structure. Indeed, one highlight
      of the past year is a new analysis of experimental results which yields a model
      of a cell membrane which need not contain any microdomains. Other highlights are
      an estimate of the number of phospholipid molecules in a membrane microdomain and
      the detection of domain formation in cell membranes in real time. Some progress
      has also been made in visualizing lipid microdomains within cell membranes. We
      still await, however, a new model of membrane structure that integrates all
      experimental results.

PMID- 9266175
TI  - Membrane proteins. Structure, assembly, and function: a panoply of progress.

PMID- 9266176
TI  - Helix packing in polytopic membrane proteins: the lactose permease of Escherichia
      coli.
AB  - Recent advances in protein engineering have facilitated the development of
      alternative approaches to determine helix packing in polytopic membrane proteins.
      Using the lac permease as a paradigm, several site-directed biophysical and
      biochemical techniques are described which should be generally applicable.

PMID- 9266177
TI  - Electron and atomic force microscopy of membrane proteins.
AB  - Electron crystallography is becoming a powerful tool for the resolution of
      membrane protein structures. The past year has seen the production of a
      bacteriorhodopsin model at 3.5 A and the structure of aquaporin 1 approaching
      atomic resolution. Determination of surface topographies of 2D crystals using the
      atomic force microscope is similarly advancing to a level that reveals
      submolecular details. As the latter is operated in solution, membrane proteins
      can be observed at work.

PMID- 9266178
TI  - Keeping calcium in its place: Ca(2+)-ATPase and phospholamban.
AB  - Electron microscopy is gradually revealing more and more about the structure of
      the calcium pump from the sarcoplasmic reticulum, Ca(2+)-ATPase. The most recent
      result reveals the ATP-binding site, and two different avenues are being pursued
      towards achieving a higher resolution structure. Although no such structures are
      currently available for phospholamban, various spectroscopies and site-directed
      mutagenesis have been combined to produce a compelling structural model for its
      regulation of Ca(2+)-ATPase.

PMID- 9266179
TI  - Protein kinase C and phospholipase C: bilayer interactions and regulation.
AB  - Protein kinase C and phospholipase C are interfacially active modular enzymes
      that contain multiple membrane-binding domains. During the past two years, 3D
      structures and functional data have been reported for the key domains: pleckstrin
      homology, protein kinase C homology-1 and -2, and the phospholipase C catalytic
      domain. Roles for membrane bilayer structure and lipid microdomains have become
      clearly domains has shown how the domains work together to coordinate regulation.

PMID- 9266180
TI  - Channel-forming toxins: tales of transformation.
AB  - Channel-forming bacterial toxins undergo a series of remarkable changes in
      solubility, oligomerization state, structure and dynamics during the processes of
      membrane binding, assembly, membrane insertion and channel formation. Recent high
      resolution crystal structures of channel-forming toxins, in both water-soluble
      and membrane-bound, channel-formed states, have brought a wealth of new
      information to bear on issues of structure, mechanism and function.

PMID- 9266181
TI  - Beef heart cytochrome c oxidase.
AB  - During the past two years, the crystal structures of beef heart cytochrome c
      oxidase with 13 subunits and the bacterial enzyme with four subunits have been
      reported at atomic resolution, ushering in a new era for cytochrome c oxidase
      research. Different proton pumping mechanisms have been proposed for the two
      organisms.

PMID- 9266182
TI  - Engineering and design.

PMID- 9266183
TI  - Lipids.

PMID- 9266184
TI  - Membrane proteins.

PMID- 9266185
TI  - A new classification for pericarditis associated with meningococcal infection.
AB  - Acute meningococcal pericarditis is a rare clinical disorder. Our review of the
      literature disclosed that current classifications are confusing since they fail
      to differentiate between two distinct criteria: time and causality. We suggest a
      new classification of the various states of meningococcal pericarditis on the
      basis of the pathophysiological process: disseminated meningococcal disease with
      pericarditis (purulent, culture-positive, associated with meningococcal
      bacteraemia); isolated meningococcal pericarditis (purulent, culture-positive but
      without signs of meningeal or other clinical systemic involvement); and reactive
      meningococcal pericarditis (immunological, late-onset, culture-negative,
      resembling post-viral pericarditis). It is essential that clinicians recognize
      the various states of the disease, since they differ in natural history,
      treatment and prognosis. CONCLUSION: From personal experience and a literature
      review it emerges that meningococcal pericarditis should be classified as: (1)
      Pericarditis as local manifestation of disseminated meningococcal disease; (2)
      isolated meningococcal pericarditis; (3) reactive (immunopathic) meningococcal
      pericarditis.

PMID- 9266186
TI  - Frequency and correlates of severe hypoglycaemia in children and adolescents with
      diabetes mellitus.
AB  - Frequency and correlates of severe hypoglycaemia have been retrospectively
      analysed in a cohort of diabetic children and adolescents with median (range) age
      14.5 (3.2-25.5) years followed from the onset of the disease by the same diabetic
      clinic. During the years 1992-1994, 53 of the 187 patients reported 74
      hypoglycaemic episodes: the average frequency of hypoglycaemia during the 3 years
      surveyed was 14.9 episodes/ 100 patients per year. Frequency of hypoglycaemia
      decreased significantly with age (chi 2 = 24.1; P < 0.0001) and was independent
      of duration of diabetes. Glycosylated haemoglobin and insulin dose were similar
      in patients with and without hypoglycaemia, matched for age and duration of
      diabetes. One out of two hypoglycaemic episodes occurred during sleep and no
      explanation was available for 50% of episodes. CONCLUSION: In this study severe
      hypoglycaemia was more frequent in young children than in adolescents and was
      independent of metabolic control and insulin dose.

PMID- 9266187
TI  - Effect of growth hormone therapy on bone metabolism of growth hormone deficient
      children.
AB  - The effects of human growth hormone (hGH) therapy on biochemical markers of bone
      metabolism were studied in 17 children (10 boys and 7 girls, aged 3.7-13.1 years
      old) with idiopathic GH deficiency, before and 1 and 6 months after GH therapy
      (0.5 0.7 IU/kg weekly SC). Serum levels of calcium, phosphate, alkaline
      phosphatase osteocalcin, parathyroid hormone, 1,25 dihydroxyvitamin D, insulin
      like growth factor I (IGF-I) and renal phosphate per 100 ml glomerular filtrate
      (TPO4/GFR) were assessed. During therapy with hGH a significant decrease of serum
      calcium levels and increases of phosphate, osteocalcin, parathyroid hormone 1,25
      dihydroxyvitamin D and IGF-I were observed. TPO4/GFR was also significantly
      increased. Growth response (increment in HV) was positively related with changes
      in alkaline phosphatase and IGF-I levels after 6 months of hGH therapy. There was
      also a significant positive correlation between increment in HV and increment in
      TPO4/GFR after 1 month of GH therapy, whereas no correlation between HV and
      changes in osteocalcin levels was found. CONCLUSION: GH treatment significantly
      influences mineral metabolism and the measurement of TPO4/ GFR after 1 month of
      GH therapy may serve as a useful predictor of growth response to hGH therapy in
      GH-deficient children.

PMID- 9266188
TI  - Auxological and endocrinological evaluation of children with hydrocephalus and/or
      meningomyelocele.
AB  - Short stature and precocious puberty are frequently found in children with
      hydrocephalus and/or meningomyelocele (MMC). However, aetiology and
      pathophysiology have not been well characterized. In this study, 108 patients
      aged between 3 and 17.8 years were evaluated. Growth was documented on the basis
      of arm span measurements. Short arm span was found in 47 (43.5%) children with
      hydrocephalus and/or MMC. Mean arm span was -2.0 standard deviation score (SDS) (
      6.4 to +0.8) in 43 girls and -14 SDS (-5.6 to +1.3) in 65 boys. When growth
      deficiency (more than -2.0 SDS) was diagnosed by arm span measurement (24 F, 23
      M) or when early sexual maturation was found (6 F, 9 M), endocrine evaluation
      followed. Levels of serum insulin-like growth factor and insulin-like growth
      factor binding protein-3 were low in 22 of 62 (33.8%) patients. In 9 of 62
      (14.5%) patients, insulin-like growth factor-1 and insulin-like growth factor
      binding protein-3 levels were found to be increased. Growth hormone (GH)
      deficiency was diagnosed by means of two different stimulation tests (clonidine
      and arginine) in 7 of 62 (11.3%) patients. In another 3 of 62 (4.8%) children, 12
      h night time GH sampling showed low maximum peak levels and decreased area under
      the curve values, suggesting neurosecretory GH dysfunction. Precocious puberty or
      early onset of puberty associated with elevated luteinising hormone and follicle
      stimulating hormone concentrations after stimulation with luteinising hormone
      releasing hormone was found in 13 of 108 (12.0%) patients (age 7-9 years). Free
      thyroxine was abnormally low in 2 of 62 (3.2%) patients. Cortisol was within the
      normal range in all 62 (100%) tested patients. CONCLUSIONS: Short arm span in
      children with hydrocephalus and/or MMC is frequently accompanied by GH deficiency
      or neurosecretory GH dysfunction. Early onset of puberty is another frequent
      finding. Both hormonal disorders may be the consequence of damage to the
      hypothalamus or the pituitary gland caused by increased intracerebral pressure or
      increased mass of cerebrospinal fluid.

PMID- 9266189
TI  - Iron overload and urinary lysosomal enzyme levels in beta-thalassaemia major.
AB  - The urinary levels of the lysosomal enzymes N-acetyl-beta-D-glucosaminidase (NAG)
      (EC 3.2.1.52) and alpha-mannosidase (EC 3.2.1.24) were evaluated in patients with
      beta-thalassaemia major and normal control subjects. Two groups of patients with
      different degrees of iron overload, as judged by their serum ferritin levels,
      were investigated. Renal disease was not present in any of the patients. A
      statistically significant increase in the levels of NAG was observed in the high
      ferritin (> 3,000 mg/dl) group compared to the low ferritin (< 3,000 mg/dl) and
      the control groups. No difference was observed in the urinary alpha-mannosidase
      levels between the groups examined. The finding of increased NAG levels in the
      patients with the increased iron load suggests that kidney lysosomes are a target
      of iron toxicity. The different behaviour of the two lysosomal enzymes may
      reflect the intra- and inter-lysosomal heterogeneity in kidney. CONCLUSION: Iron
      overload resulted in increased urinary levels of the lysosomal enzyme NAG which
      has been proposed as an early marker of kidney damage. Reduction of iron load,
      achieved by regular desferrioxamine infusion, resulted in normalisation of the
      urinary enzyme levels. Thus kidney lysosomes appear to be a target and possibly a
      mediator of iron toxicity in this tissue.

PMID- 9266190
TI  - Glucose phosphate isomerase deficiency: biochemical and molecular genetic studies
      on the enzyme variants of two patients with severe haemolytic anaemia.
AB  - Biochemical and molecular genetic studies were performed on the enzyme variants
      of two patients compound heterozygous for glucose phosphate isomerase (GPI)
      deficiency, both suffering from severe haemolytic anaemia. The enzymes of case 1
      (GPI 'Zwickau') and case 2 (GPI 'Nordhorn' [25]), revealed reduced GPI activity
      and remarkable thermolability. Glucose-6-phosphate (Gluc-6-P) concentration was
      elevated 2.3 times in case 1 and 3.8 times in case 2. Sequencing the patients'
      GPI genes showed four different point mutations, two of them involving highly
      conserved amino acids. The c1039 C-->T substitution, found in the gene of GPI
      'Zwickau', has been described recently [30] and causes an Arg 347-->Cys
      substitution close to the putative catalytic site. The second mutation in this
      case is a novel c1538 G-->A substitution causing a Trp-->stop mutation at
      position 513 apparently resulting in premature RNA degradation thus resulting
      either in a complete lack of protein or a protein which does not show GPI
      activity. In the gene of GPI 'Nordhorn' a c1028 A-->G mutation was discovered,
      also previously described [1, 9] causing a Gln 343-->Trp substitution. The second
      mutation was a novel splice site mutation at the border of intron 15 to exon 16:
      IVS15-(-2) A-->C which leads to an aberrant splicing of exon 16, thus resulting
      either in a truncated and most likely inactive enzyme or in no protein at all.
      CONCLUSION: Biochemical and molecular genetic studies performed with the enzyme
      variants GPI 'Zwickau' and GPI 'Nordhorn' showed that in both cases the
      simultaneous occurrence of a single amino acid substitution affecting the active
      site, together with a nonsense mutation leading to the loss of major parts of the
      enzyme probably explains the severe clinical course of the disease.

PMID- 9266191
TI  - Diagnostic imaging in abdominal neuroblastoma: is there a complementary role of
      MIBG-scintigraphy and ultrasonography?
AB  - In a retrospective study we evaluated the agreement between the results of meta
      iodo benzylguanidine (MIBG) scintigraphy and abdominal ultrasonography (US) in
      the diagnosis and follow up of neuroblastoma (NBL) with respect to the abdominal
      region. Data of 28 consecutive paediatric patients with NBL or suspected NBL were
      included (16 M/12 F, mean age 2.9 years, range 3 weeks-13.4 years). The results
      (as judged by the nuclear physician or radiologist, respectively) of 60 MIBG
      examinations (123I and 131I) including 26 single photon emission computed
      tomography (SPECT) and US, respectively, performed within a period of 14 days,
      could be evaluated. Full agreement was reached in 37 comparisons (62%), while
      partial and no agreement was found in 17 (28%), and 6 (10%) comparisons
      respectively. In 8 out of 37 comparisons with full agreement, 12 diagnosed
      lesions were histopathologically proven, while 11 comparisons with negative
      findings were also negative in other clinical modalities. US diagnosed correctly
      in 68% of the histopathological proven lesions, while this was 54% for MIBG
      scintigraphy. In approximately 50% of the MIBG scans in which SPECT was
      available, SPECT provided significant additional information. CONCLUSION:
      Congruent results of MIBG scintigraphy and ultrasonography in the detection of
      abdominal lesions in patients with suspected neuroblastoma indicate a high
      reliability in the diagnosis and localisation. Due to the favourable results of
      additional SPECT, it is advisable to perform SPECT routinely in this diagnosis.

PMID- 9266192
TI  - Anti-endomysium antibody on human umbilical cord vein tissue: an inexpensive and
      sensitive diagnostic tool for the screening of coeliac disease.
AB  - Anti-endomysium antibody (AEA) was evaluated in 136 subjects by indirect
      immunofluorescence using both cryosections of monkey oesophagus (MO) and the
      human umbilical cord vein (HUCV) as substrate. This human tissue gave results
      comparable to those of MO. In particular, the HUCV sections showed positive
      results in all 22 newly diagnosed cases of coeliac disease. Compared to the MO
      sections, the sensitivity, specificity and positive predictive values of HUCV
      tissue was 100%. CONCLUSION: HUCV tissue can replace MO for AEA detection and can
      make the screening for coeliac disease easier both in at-risk and in normal
      populations, with a remarkable saving, both in terms of money and of monkeys.

PMID- 9266194
TI  - Chronic infantile neurological cutaneous articular syndrome in a patient from
      Japan.
AB  - A case of chronic infantile neurological cutaneous articular (CINCA) syndrome in
      a Japanese girl, started at the age of 13 days with episodes of fever, rash
      followed by swollen joint, hepatosplenomegaly, generalized lymphadenopathy and
      chronic central nervous system involvement, is reported. Some of the findings
      suggest that this syndrome may be the result of an intrauterine infection. This
      is the first case of CINCA syndrome in a Japanese girl.

PMID- 9266193
TI  - Familial Mediterranean fever in children: report of a large series and discussion
      of the risk and prognostic factors of amyloidosis.
AB  - Familial Mediterranean fever (FMF) is a genetically transmitted disease
      characterized by recurrent attacks of fever and serositis. The most important
      complication of this disease is the development of amyloidosis. We present our
      analysis of 425 FMF patients without and 180 with amyloidosis (123 FMF having
      amyloidosis type 1 and 57 FMF having amyloidosis type II). The male female ratio
      was higher in the amyloidosis population (111/69) when compared to the FMF
      population (225 200) (P = 0.048). Consanguinity rate was the same among FMF and
      amyloidosis groups. However, a family history of amyloidosis was significantly
      more frequent in the amyloidosis group (P = 0.00001). Multivariate analysis has
      revealed that in FMF patients, the presence of a family history of amyloidosis
      plus consanguinity has a 6.04 fold increased risk of amyloidosis (P < 0.0001).
      The 5-year chronic renal failure free survival was 43.1% and 18.7% in type I and
      type II amyloidosis, respectively. The time interval to develop chronic renal
      failure after the development of amyloidosis was 4.8 in type I and 3.0 years in
      type II. respectively. We found ten cases of Henoch-Schonlein Purpura and nine of
      polyarteritis nodosa among our patients. The significance of the association
      between FMF and vasculitis awaits to be clarified. Among the FMF patients put on
      colchicine therapy (435), only 10 (2.3%) have developed amyloidosis confirming
      that this drug protects from amyloidosis. CONCLUSION: Since the presence of a
      familial history of amyloidosis has been defined as the most important risk
      factor in the development of amyloidosis, we suggest that additional genetic
      factors may be operative in the development of amyloidosis.

PMID- 9266195
TI  - Axial spondylometaphyseal dysplasia.
AB  - We present a previously undescribed skeletal dysplasia characterized by mild
      platyspondyly, small thorax with cupping of the anterior ends of the ribs,
      irregular proximal femoral metaphyses, and lacy appearance of the iliac wings.
      Two of the three cases were siblings. Retinitis pigmentosa and optic atrophy are
      associated findings. CONCLUSION: We describe a new type of spondylometaphyseal
      dysplasia (SMD) and propose the name axial SMD.

PMID- 9266196
TI  - Osteopathia striata, short stature, and characteristic facies: a previously
      unknown skeletal dysplasia.
AB  - We report two sporadic cases of a hitherto undescribed skeletal dysplasia with
      short stature and characteristic facies. The present patients, a 6-year-old girl
      and a 15-year-old boy, were almost equally affected. Craniofacial anomalies
      included a sloping forehead, bitemporal bulging, sparse medial eyebrows, a
      prominent nasal bridge, hypertelorism, proptosis, a beaked nose, hypoplastic alae
      nasi and a pointed chin. Shallow orbits, short anterior cranial fossae and
      bitemporal bossing found on skull radiograph corresponded with the facial
      dysmorphism. Thickening of the dorsum sellae was another hallmark in the skull.
      Skeletal survey revealed mild osteopenia, interpediculate narrowing of the lumbar
      spine with short neural arches and, most important, osteopathia striata of the
      long tubular bones. There was no sclerosis of the craniofacial bones. The
      clinical and radiological findings in the present patients were overall
      inconsistent with those of previously known skeletal dysplasias and congenital
      malformation syndromes, which possess osteopathia striata as a cardinal feature.
      CONCLUSION: The unique clinical and radiological constellation of our patients
      constitutes a hitherto unknown bone dysplasia.

PMID- 9266197
TI  - Severe feeding problems and congenital laryngostenosis in a patient with 3q23
      deletion.
AB  - Common clinical features of patients with 3q23 deletion include the phenotype of
      BPES (blepharophimosis, ptosis, epicanthus inversus and telecanthus syndrome),
      growth and mental retardation, microcephaly ear and nose dysmorphism and joint
      and digit abnormalities. We report on a 3-year-old girl with the phenotype of
      BPES, mental retardation, facial dysmorphism and camptodactyly. In addition, she
      had a congenitally small larynx and severe, chronic feeding difficulties.
      Chromosome studies revealed an interstitial deletion in the long arm of
      chromosome 3: del(3)(q23-q25). CONCLUSION: Congenital laryngostenosis and severe
      feeding problems may be part of the clinical syndrome caused by chromosome 3q23
      deletion.

PMID- 9266198
TI  - Response to nitric oxide in term and preterm infants.
AB  - The response to three levels (10 ppm, 20 ppm and 40 ppm) of nitric oxide (NO) was
      assessed in 30 infants, median gestational age 30 (range 24-42) weeks. All the
      infants required an inspired oxygen concentration of more than 0.5, despite
      receiving surfactant where appropriate. All but one infant had a positive
      response to NO (median reduction in the oxygenation index (OI) was 33%, range -9%
      90%), but only 20 infants showed a greater than 20% reduction in the OI. There
      was no obvious relationship of the optimum NO level (i.e. that associated with
      the maximum reduction in OI) and either diagnosis (congenital diaphragmatic
      hernia, meconium aspiration syndrome, respiratory distress syndrome, pulmonary
      interstitial emphysema (PIE), hydrops and sepsis) or maturity, except that five
      of six infants with PIE responded best to 40 ppm, as did eight of nine infants
      less than 28 weeks gestational age. We conclude NO dosage should be
      individualized and NO levels up to 40 ppm should be considered in very immature
      infants.

PMID- 9266199
TI  - The in vivo effect of recombinant human granulocyte-colony stimulating factor in
      neutropenic neonates with sepsis.
AB  - The effects of recombinant granulocyte-colony stimulating factor (rhG-CSF) in
      neonatal neutropenia with presumed sepsis, which has a poor prognosis, were
      investigated. The study involved 14 neonates with presumed sepsis and
      neutropenia. Findings were compared with those from 24 historical controls. rhG
      CSF (5 micrograms/ kg/day i.v. for 5 days) was administered immediately following
      diagnosis. Complete blood counts were obtained before and 24, 48, 72, 96 and 120
      h after initiation of treatment. Neutrophil storage pool (NSP) was assessed (in 4
      patients) before and after treatment. Statistical analysis was performed using
      one way analysis of variance. Treatment led to an increase in absolute neutrophil
      count (ANC) levels in 13/14 patients. At the end of treatment, the mean ANC was
      higher than that of controls (P = 0.007). There was a marked increase in the NSP
      of between 32% and 65% (P = 0.005). There were two clinical failures, one of whom
      was considered to have died from his underlying condition. There were no reports
      of clinical or haematological toxicity during treatment or follow up.

PMID- 9266200
TI  - Pulmonary thrombo-embolism in nephrotic syndrome treated with tissue plasminogen
      activator.
AB  - We describe the case of a boy with steroid sensitive nephrotic syndrome and left
      pulmonary artery thrombo-embolism. clinical presentation initially suggested
      sepsis and respiratory signs were minor. Treatment with tissue plasminogen
      activator infused into the pulmonary artery was successful. CONCLUSION: Pulmonary
      thrombo-embolism should be considered in unwell children with nephrotic syndrome.

PMID- 9266201
TI  - Selective screening of 10,000 high-risk Brazilian patients for the detection of
      inborn errors of metabolism.
AB  - The number of diagnosed inborn errors of metabolism (IEM) is growing constantly
      due to the improvement and widespread availability of analytical techniques. In
      1982, a laboratory for the detection of IEM was set up in Porto Alegre, Brazil,
      and became a national reference centre for the diagnosis of these disorders. Ten
      thousand patients with signs and symptoms suggestive of IEM were investigated in
      our laboratory from 1982 to 1995 using specific protocols which included tests
      for the detection of glucosaminoglycans (GAGS), amino acids, sugars,
      oligosaccharides, sialyloligosaccharides, organic acids, as well as various
      metabolite. The biochemical investigation was completed in 9,901 patients and an
      IEM was detected in 647 cases (6.5%). Groups of IEM of higher incidence in our
      sample were lysosomal storage disorders (59.8%) and aminoacidopathies (21.2%).
      The disorders most frequently diagnosed were classical phenylketonuria, GM1
      gangliosidosis, mucopolysaccharidosis type I, mucopolysaccharidosis type VI and
      metachromatic leukodystrophy. CONCLUSION: This study shows that the establishment
      of reference centres for the investigation of rare genetic diseases is a suitable
      approach to the study of IEM in developing countries such as Brazil.

PMID- 9266202
TI  - Epidemiological features of sudden infant death after a German intervention
      campaign in 1992.
AB  - After national intervention campaigns, considerable declines in incidence for
      both sudden infant death (SID) and prone position have been observed worldwide.
      In the following investigation. German data on postinterventional risk factor
      patterns are presented for the first time. We analysed data from a 2-year
      population-based case-control study on SID carried out in two German districts
      between 1993 and 1994. We confirmed Complete covering of the baby (OR = 44.9, 95%
      CI 95, 291), prone sleeping position (OR = 11.7; 5.3, 26.2), heavy maternal
      smoking during pregnancy (OR = 8.5; 3.2, 33.2 for > ten cigarettes per day),
      nonbreastfeeding (OR = 7.7; 2.7, 22.3) and missing maternal professional training
      (OR = 7.6; 3.6, 16.2) as risk factors for cot death. After adjustment for other
      major risk factors in a logistic regression model, sleeping on cushions lost
      statistical significance, whereas all other major risk factors remained relevant.
      CONCLUSIONS: Despite intervention campaigns, complete covering of the baby, prone
      position and heavy maternal smoking are still major risk factors for cot death.
      Except for sleeping on cushions, all major epidemiological risk factors for cot
      death act independently. Despite encouraging success in the reduction of risk
      factors for cot death, there is still substantial need for future endeavours
      towards a further reduction of modifiable risk factors for SID.

PMID- 9266203
TI  - Case of the month. A 3.5-year-old female with developmental delays, hepatomegaly,
      and coarse facies.

PMID- 9266204
TI  - Antifungal agents in neonatal systemic candidiasis.

PMID- 9266205
TI  - Urinary nitrite/nitrate levels in children with bronchial asthma.

PMID- 9266206
TI  - Hyponatraemia and cerebral convulsion due to DDAVP administration in patients
      with enuresis nocturna or urine concentration testing.

PMID- 9266207
TI  - Stable isotopes in biosciences, their measurement and models for amino acid
      metabolism.
AB  - In order to follow the movement and quantify the metabolic fates of biologically
      important molecules in vivo, both tracers and kinetic modeling are required. For
      the study of intermediary metabolism in children, stable isotopically labeled
      substrates satisfy both the analytical and ethical requirements for tracer use in
      children. Stable isotope tracers have been proven safe over more than a half
      century of use in humans. In addition, mass spectrometric analysis of stable
      nuclide molecular position and isotopic enrichment in biological molecules is
      both highly specific and extraordinarily precise. Using stable isotope data to
      develop models of biological system dynamics in vivo is an essential element of
      estimating substrate events that take place in cells or organs otherwise
      inaccessible for ethical sampling in children. Further, modeling is also a
      critical component in the development and the testing of hypotheses about the
      structure of the biological system in question and the mechanisms which control
      its operational parameters.

PMID- 9266208
TI  - Availability of stable isotope tracers for human use.
AB  - Stable isotope tracers do not have approval for diagnostic use in humans. We
      assume that stable isotope tracers behave like natural compounds, because there
      is no evidence for the opposite despite a wide use in human studies. From this
      point of view, they are drugs comparable to unlabelled natural substances. Under
      this assumption a pharmacy is allowed to prepare isotope solutions by following
      the guideline for the preparation of infusion solutions using chemicals. The
      pharmacy has to perform tests for identification, content and purity following
      the U.S. pharmacopoeia or the corresponding national standard for the unlabelled
      drug. If these tests are passed then it can prepare the tracer solution. An
      approach is outlined which is designed to ensure sterility of the preparation as
      far as possible and an adequate pharmaceutical quality. From the regulation for
      the preparation we define requirements for an alternative preparation for
      immediate infusion by the physician.

PMID- 9266209
TI  - Safety of stable isotope use.
AB  - The increased employment of stable isotope tracers for diagnostic and research
      purposes frequently raises questions on potential risks associated with their
      use, which is of particular importance in the paediatric age group. Biological
      effects and the potential of adverse events has been evaluated in a large number
      of animal and, in part, also human studies. Possible differences in physical,
      chemical and biochemical behaviour resulting in kinetic and thermodynamic isotope
      effects between stable isotopes of the same element are related to the relative
      differences in atomic weight. Deuterium (2H), which differs markedly in mass from
      the predominant hydrogen isotope 1H, may induce serious side-effects at high
      concentrations in body fluids. The threshold dose for the occurrence of side
      effects lies well above the usual tracer dosages for clinical use. In contrast to
      deuterium, heavier stable isotopes such as 13C, 15N or 18O that differ relatively
      little in mass from the predominant isotopes such as 12C, does not show any
      adverse biological effects even at highest enrichments. CONCLUSION: The doses of
      stable isotope tracer substances that are used for clinical diagnostic and
      research purposes appear safe and without any adverse effects. Stable isotope
      tracers should only be used in children if the trace is safe at the doses
      applied, and tracer is chemically pure and stable. In the case of intravenous
      application, the tracer preparation must also be sterile and pyrogen free.

PMID- 9266210
TI  - Breath tests: concepts, applications and limitations.
AB  - Breath tests (BT) using stable isotopically labelled substrates seem to fulfill
      all the demands and desires for a non-invasive investigation. There are no
      radiation hazards, substrates are given in tracer amounts perorally, breath and
      urine samples can be collected easily, and tests can be done repeatedly, thus
      easily allowing the monitoring of function with time. There are, however, some
      disadvantages. Any BT has the same assumption: after intake of the 13C tracer the
      substrate is metabolized to 13CO2. An increase of 13CO2 above baseline levels is
      said to reflect the function investigated-in 13C sucrose studies, the amount of
      carbohydrate absorbed; in 13C aminopyrine BT, the liver function; in 13C glucose
      BT in a diabetic child, the impaired handling of glucose. However, as only the
      end product 13CO2 is measured, there is no information on all the pools and
      fluxes the labelled substrate and its metabolites have to pass. At least in
      inborn errors of metabolism, probably in any disease, one has to assume that
      these fluxes and pools are substantially changed. Therefore all calculations are
      weak and finally one has to resort to invasive methods, i.e. drawing blood to
      measure pools and fluxes to allow a correct interpretation of the BT data.
      Furthermore, changes in the basal exhalation of 13CO2 during the test will have
      an impact on the BT calculation. Another problem is that for an exact
      calculation, the basal metabolic rate (BMR) and the actual endogenous CO2
      production in the patient is needed, which in most instances is unknown. It is
      not easy to maintain a stable endogenous CO2 production, particularly in younger
      children who will not rest or in neonates and toddlers who may fight against
      taking breath samples. Taking together these limitations are the reason why BT
      have not been able to reach the level of routine clinical methods, especially in
      the diagnostic work up of impaired liver function or inborn errors of metabolism.

PMID- 9266211
TI  - Assessment of energy expenditure in metabolic disorders.
AB  - The assessment of energy expenditure is valuable for the management of children
      with various conditions such as obesity and failure to thrive. Total daily energy
      expenditure (TDEE) includes resting energy expenditure (REE), energy expenditure
      during physical activity, dietary thermogenesis and growth. TDEE can be assessed
      by using the double-labelled water technique, but it has complex pitfalls and
      potential sources of errors and is impractical for everyday use. As REE is a
      substantial part of TDEE (65%-70%) and computerised indirect calorimeters have
      become recently available, this non-invasive, relatively cheap and easy to use
      technique is valuable for the assessment of short-term changes in energy
      metabolism. This can be used to assess REE of children with inborn errors of
      metabolism, whilst well and during episodes of metabolic decompensation and
      therefore to accurately determine energy intake.

PMID- 9266212
TI  - Iron, copper, and zinc absorption and turnover; the use of stable isotopes.
AB  - This overview demonstrates the increasing use of low natural abundance stable
      isotopes in the investigation of mineral metabolism. There are many practical
      problems associated with their use and analysis and their expense has limited
      their application in some areas such as studies in adults. Undoubtedly we will
      have to assess our ideas and protocols as the practical problems and their
      metabolic implications become better appreciated but none the less, the use of
      such isotopes will certainly refine our understanding of the way the body uses
      elements such as zinc, copper, iron and selenium and other essential elements and
      will enable us to determine our dietary requirements for these nutrients and to
      find ways of detecting more efficiently early deficiency and toxicity states.

PMID- 9266213
TI  - Measurement of glucose turnover--implications for the study of inborn errors of
      metabolism.
AB  - Aspects of glucose metabolism have been investigated quantitatively employing
      stable isotopes for 20 year. Use of non-recycling [6,6-2H2] or [U-13C] glucose
      labels provides a value for total hepatic glucose production (glycogenolysis plus
      gluconeogenesis). Quantitation of gluconeogenesis with isotopic tracers has
      itself recently been revisited employing protocols and analytical options that
      purport to overcome the isotope exchanges (dilution) experienced at the level of
      oxaloacetate when the rate of incorporation of label into glucose from infused
      alanine, lactate or pyruvate is monitored. Labelled glucose has been employed to
      investigate metabolic disturbances of glycogen storage disease type I (GSD-I) and
      type III (GSD-III). Endogenous glucose production and glucose recycling have been
      studied in both these storage diseases employing a primed-continuous infusion of
      D-[U-13C] glucose and quantitation of isotope enrichments and isotopomer
      distribution observed in plasma glucose either by mass spectrometry or nuclear
      magnetic resonance spectroscopy. General aspects of glucose metabolism as
      investigated with stable isotopes are presented.

PMID- 9266214
TI  - Dietary treatment in late-onset acid maltase deficiency.
AB  - Late-onset acid maltase deficiency or glycogen storage disease type II (GSD II)
      is a rare disorder of intralysosomal glycogen metabolism, resulting in
      progressive myopathy that is secondary to increased muscle protein breakdown.
      Stable isotope studies in the postabsorptive state have confirmed that mean
      protein breakdown in GSD II is increased by 31% compared to control subjects.
      6.86 versus 4.69 g/kg per day, that mean protein balance is reduced is GSD II 
      1.32 versus -1.06 g/kg per day. Indirect calorimetry has demonstrated an increase
      in mean resting energy expenditure in GSD II, 41.8 versus 31.2 kcal/kg per day.
      Compliance following the introduction of a high-protein diet is often poor due to
      the large quantities of protein necessary and to the high caloric intake with the
      consequent weight gain. Only 25% of all reported subjects with GSD II showed an
      improvement of muscle or respiratory function after a high-protein diet. Careful
      evaluation of the underlying pathophysiological changes in GSD II is necessary to
      develop more logical and therefore more beneficial forms of dietary treatment.

PMID- 9266215
TI  - Quantitative assessment of whole body galactose metabolism in galactosemic
      patients.
AB  - We employed [1-13C] galactose in isotope kinetic studies to delineate whole body
      galactose metabolism in vivo in patients with galactose-1-phosphate
      uridyltransferase (GALT) deficiency. The data in three control and three adult
      galactosemic subjects, homozygous for the most common GALT gene defect, the Q188R
      mutation, and with absent RBC GALT activity, revealed an apparent endogenous
      galactose synthesis rate of 0.53-1.05 mg/kg per hour. Unlike normal children and
      adults who eliminated 3%-6% and 21%-47% of an intravenous bolus of [1-13C]
      galactose as 13CO, in expired air in 1 and 5 h respectively, classic galactosemic
      patients, either Q188R/Q188R or Q188R/unknown, released almost none in 1 h and 3%
      6% in 5 h. In contrast, an African-American galactosemic variant patient with a
      S135L/S135L mutation and no residual RBC GALT activity oxidized [1-13C]galactose
      to 13CO2 at a rate comparable to control subjects. Individuals homozygous for the
      Duarte mutation, N314D/N314D and Q188R/ N314D. Q188R/+ and S135L/+ subjects also
      had normal breath test results. Not surprisingly, the Q188R/Q188R classic
      galactosemic patient cannot handle an acute galactose load, failing to match a
      control subject in the rapid conversion of [1-13C]galactose to [13C]glucose and
      13CO2. However, classic patients synthesize substantial quantities of galactose
      de novo and on a lactose-free diet must oxidize comparable amounts of galactose
      to maintain steady-state levels of galactose and galactose metabolites such as
      galactose-1-phosphate, galactitol and galactonate. In vivo isotope kinetic
      analyses may allow us to understand better these aspects of galactose metabolism
      and, through the use of studies in variant galactosemics, perhaps allow us to
      begin to unravel the pathophysiology of galactosemia.

PMID- 9266216
TI  - Integration of amino acid and carbon intermediary metabolism: studies with
      uniformly labeled tracers and mass isotopomer analysis.
AB  - The central pathways of metabolism include glycolysis and gluconeogenesis, fatty
      acid synthesis and beta-oxidation, the citric acid cycle and ureagenesis. Because
      these pathways intersect, changes in one pathway, due to inborn error or disease,
      affect pathways that may seem remote from the initial metabolic defect. These
      metabolic interrelationships also present difficulties for isotopic studies,
      because once carbon derived from isotopic tracers is introduced into metabolism
      it is extensively recycled. The use of multiple labeled (especially uniformly 13C
      labeled ([U-13C]), metabolic tracers, in conjunction with mass isotopomer
      distribution analysis of mass and nuclear magnetic spectra, has enabled the
      development of methods that resolve some of these difficulties. Suitable choices
      of tracers and analytes allow the simultaneous measurement of multiple pathways
      and, importantly, their kinetic interrelationships. We illustrate three uses of
      the technique: (1) the unequivocal determination of trace fluxes; (2) the
      quantification of biosynthetic pathways: and (3) the dissection, in vivo, of the
      citric acid (Krebs) cycle. In each case, different combinations of [U-13C]tracer
      and metabolic end product have revealed metabolic phenomena that otherwise would
      remain unidentified. A particularly striking, and unexpected, observation that
      has emerged from recent studies using the technique, suggests that the key
      dehydrogenase reactions in the Krebs cycle may be reversible. Although this
      approach is of relatively recent development, it has already given a number of
      novel insights into the organization of the central metabolic pathways. It should
      provide a powerful method of investigating the metabolic impact of genetic
      disease and provide invaluable support of the assessment of new therapeutic
      interventions.

PMID- 9266217
TI  - Protein turnover in critically ill children.
AB  - There is a paucity of data documenting the metabolic response to catabolic stress
      in childhood in general and about protein turnover in critically ill children in
      particular. Despite a high overall morbidity and mortality rate there is little
      information on which to base decisions to improve the management either by
      dietary therapy or by use of growth factors. Protein turnover is a key metabolic
      process that significantly alters during the catabolic state. Protein kinetics
      are easy to quantify using various stable isotope models, with some having
      advantages in the critically ill child. The 1-13C leucine technique is the most
      widely used and best validated model to date, requiring accurate estimation of
      CO2 production. There is also uncertainty about the bicarbonate kinetics and pool
      sizes in ventilated children whose respiratory function is severely impaired. The
      value of the 15N glycine (end product) technique is more limited because the time
      to achieve isotopic equilibrium is lengthy and considerable concerns about the
      validity of the model exist. The ring-D5 phenylalanine technique has the
      advantage of not requiring the measurement of CO2 production or 13C enrichment,
      but the model has not yet been validated in critically ill children. Despite it
      is of obvious value to measure protein turnover, few studies in critically ill
      children have been done.

PMID- 9266218
TI  - Metabolism of branched-chain amino acids in maple syrup urine disease.
AB  - Maple syrup urine disease (MSUD) is an autosomal recessive disorder. Impaired
      activity of the branched-chain 2-oxo acid dehydrogenase complex (BCOA-DH) causes
      accumulation of branched-chain L-amino (BCAA) and 2-oxo acids (BCOA) that can
      exert neurotoxic effects. MSUD presents as a heterogeneous clinical and molecular
      phenotype. Severity of the disease, ranging from classical to mild variant types,
      is commonly classified on the basis of indirect parameters, e.g. onset, leucine
      tolerance and/or residual enzyme activity in cells. Available information on BCAA
      turnover in vivo suggests that renal clearance is low and that the main route of
      BCAA disposal in MSUD is via protein synthesis, similar to healthy subjects.
      Information on BCAA oxidation is poor. In vivo oxidation rates have been assessed
      in a few studies in patients with claimed classical form of MSUD, using (stable)
      isotopically labelled L-leucine and both the (primed) continuous infusion and the
      oral bolus test approach. However, highly variable results have been obtained
      with both methods not only with respect to the number of patients exhibiting
      measurable leucine oxidation (range: 0%-100%; two to seven patients investigated)
      but also considering the extent of residual whole body leucine oxidation (range:
      < or = 2%-43% of control). Whether the different findings on whole body leucine
      oxidation actually reflect the variability of in vivo severity in classical MSUD
      as opposed to the measurements in cultured cells (generally < or = 2% of
      control), alternative pathways of leucine oxidation in some patients or were
      rather attributable to inadequate classification of patients or/and to inherent
      methodological problems remains to be clarified.

PMID- 9266219
TI  - Stable isotope studies in propionic and methylmalonic acidaemia.
AB  - Stable isotope techniques have been used to measure propionate production and
      disposal in patients with propionic and methylmalonic acidaemia. There are wide
      variations between individual patients but aminoacid catabolism accounts for
      approximately 50% of propionate production, bacterial activity in the gut 25% and
      catabolism of odd chain fatty acids 25%. Oxidation of propionate is an important
      route of disposal. These studies have helped to improve the management of inborn
      errors of propionate metabolism.

PMID- 9266220
TI  - New insights into lipid and fatty acid metabolism via stable isotopes.
AB  - Dynamic processes are of great interest in the study of lipid and fatty acid
      metabolism. Their in vivo investigation is now possible with the use of stable
      isotope tracers and the available sensitive analytical technology. We present
      some examples demonstrating the assessment of lipid oxidation as well as
      modulating factors by analysis of the tracer appearance in breath CO2 by isotope
      ratio mass spectrometry (IRMS). In a child with severe hypertriglycendaemia due
      to decreased cleavage of chylomicrons, medium-chain triglycerides were oxidised
      normally, whereas utilisation of long-chain triglycerides was severely disturbed.
      In another patient with primary carnitine deficiency, the beneficial effect of
      carnitine supplementation on fat oxidation could be demonstrated. In combination
      with gas chromatography, the high sensitivity of IRMS may be used for the
      detection of tracer materials in various plasma metabolites. In a pilot study, we
      applied C-13C labelled linoleic and alpha-linolenic acids to infants aged 2 weeks
      and 11 months, respectively. In these subjects, we could show a relative decrease
      of the conversion of these essential fatty acids to their longer chain
      polyunsaturated derivatives with age. The ability of term infants aged 19 days to
      convert linoleic into arachidonic acid was evaluated by using small natural
      differences in 13C abundance between different foods. Stable isotopes are also
      suitable for elucidation of new metabolic pathways. As an example, we could show
      in rats that linoleic and alpha-linolenic acids, which are usually considered to
      be essential substrates, can be synthesized endogenously from C16 precursors.
      CONCLUSION: IRMS is well suitable for the clinical investigation of lipid
      metabolism with stable isotopes in children. With different sample preparation
      devices, breath CO2 as well as specific plasma components can be analysed. While
      breath tests are already applied in clinical routing testing, GC-C-IRMS is a
      promising tool for research.

PMID- 9266221
TI  - Studies of apolipoprotein B-100 metabolism using radiotracers and stable
      isotopes.
AB  - Apolipoprotein B metabolism can be investigated in-vivo either by exogenous
      radiolabeling of preformed lipoproteins or by endogenous labelling of denovo
      synthesized apo B using a stable isotope substituted amino acid tracer. The
      potential of both methods and results obtained by in-vivo studies in genetically
      determined dys- or hyperlipidaemic subjects will be discussed.

PMID- 9266222
TI  - In vivo stable isotope studies in three patients affected with mitochondrial
      fatty acid oxidation disorders: limited diagnostic use of 1-13C fatty acid breath
      test using bolus technique.
AB  - The in vivo oxidation of fatty acids (FA) of different chain length was
      investigated in three patients with documented mitochondrial FA oxidation
      disorders: one patient with mild multiple acyl-CoA dehydrogenase deficiency
      (MADM), one with medium chain acyl-CoA dehydrogenase deficiency (MCAD), and one
      with carnitine palmitoyltransferase I deficiency (CPT I). Breath tests were
      performed after oral administration of 1-13C butyric. 1-13C octanoic, and 1-13C
      palmitic acids. 13C/12C ratio in the expired oxidative end product CO2 was
      measured. The cumulative 13C elimination was calculated and expressed as a
      percentage of the administered dose. In the MADM patient the influence of
      carnitine therapy (or deprivation) on the utilization of 1-13C palmitic acid was
      also examined. In the MCAD and CPT I patients, the 1-13C butyric, 1-13C octanoic
      and 1-13C palmitic acids in vivo oxidation were similar to five healthy controls.
      In the MADM patient, the oxidation of 1-13C butyric and 1-13C octanoic acids were
      normal, whereas the metabolism of 1-13C palmitic acid ranged from 33% of 66% of
      controls. In this patient the serum carnitine level decreased from 60 to 27
      mumol/l without carnitine supplementation. Clinically there was mild hypotonia. 1
      13C palmitic acid oxidation compared to controls was 50%. After 2 further weeks
      of carnitine deprivation the serum carnitine was 10-15 mumol/l. Clinically he was
      very hypotonic and had a large liver. 1-13C Palmitic acid oxidation was 33%.
      After 6 weeks of readministration of carnitine (L-carnitine 100 mg/kg/day p.o.)
      the serum carnitine was 60 mumol/l and the patient was in good clinical
      condition. 1-13C palmitic acid oxidation was 66% compared to controls. Our study
      implies that this simple fatty acid breath test is not of diagnostic use for
      detection of enzymatic defects in FA oxidation disorders. The carnitine dependent
      1-13C palmitic acid oxidation indicates that this test might be of some value in
      cases with primary or secondary carnitine deficiencies.

PMID- 9266223
TI  - Stable isotope studies of phytanic acid alpha-oxidation: in vivo production of
      formic acid.
AB  - The aim of this study was to test whether formate is formed during alpha
      oxidation of phytanic acid in humans. To a healthy volunteer, [1-13C]phytanic
      acid was given as an oral substrate in a dose of 15 mg/kg body weight, after
      which plasma, urine and breath air samples were collected during 35 h. The plasma
      concentrations of [1-13C]-phytanic acid, 2-hydroxy[1-13C]phytanic acid, pristanic
      acid and [13C]formate were analysed. The [1-13C]phytanic acid concentration
      increased within 5-7 h to 105 mumol/l, then decreased. Formation of 2-hydroxy[1
      13C]phytanic acid increased during the first 11 h after which it decreased during
      the next 20 h. Pristanic acid increased slightly during the test. In breath air,
      13CO2 enrichment was measured, showing a cumulative output of ca. 30% of the
      ingested dose after 35 h. In both urine and plasma, enrichment of [13C]formate,
      higher than that of 13CO2 was demonstrated. These findings show that formate is a
      decarboxylation product in the alpha-oxidation of phytanic acid in vivo.

PMID- 9266224
TI  - Stable isotope studies in inborn errors of metabolism--implications and
      conclusions.
AB  - Stable isotope studies have considerable potential to help understand the
      biochemistry and pathophysiology of inborn errors of metabolism but this has not
      yet been fully realised. It is to be hoped that this symposium will prove to be a
      valuable stimulus to this field of research.

PMID- 9266225
TI  - Up-to-date management of carcinoma of the penis.
AB  - Squamous cell carcinoma is the most common tumour of the penis. It is a rare
      disease in Western countries, and it is often associated with phimosis, poor
      hygiene or human papilloma virus infection. It could be prevented or diagnosed
      early in most cases, but, due to cultural and educational reasons, it is often
      diagnosed late. Nodal metastases are relatively common, but distant dissemination
      is very rare. Radical surgery gives the best control of the primary tumour, but
      it is mutilating. Laser surgery for limited superficial lesions and sophisticated
      radiotherapy for relatively small infiltrating tumours have been successfully
      employed, alone or in combination with chemotherapy. The use of radical surgery
      can therefore be restricted to cases which are unsuitable for conservative
      treatment or to relapses. Survival mainly depends on nodal metastases, but
      management of regional lymph nodes is controversial. Radical inguinal or
      ileoinguinal lymphadenectomy can cure approximately 40-50% of patients with
      positive nodes, but nearly half of the patients with clinically enlarged nodes
      actually have no metastases. Invalidating oedema is a frequent complication of
      inguinal lymphadenectomy. The point is to restrict the operation to patients with
      positive nodes. Expectant policy can be dangerous because results of delayed
      lymphadenectomy are usually poor. Fine needle aspiration biopsy and imaging may
      be of help in diagnosing nodal metastases. Modified surgical procedures have been
      advocated in order to obtain a pathological staging of the inguinal nodes
      avoiding invalidating sequelae, but results are controversial. Depth of invasion,
      tumour grade and growth pattern are of help in identifying patients at a very
      high risk of harbouring nodal metastases. Squamous cell carcinoma of the penis is
      relatively responsive to chemotherapy. Limited experiences suggest that adjuvant
      chemotherapy can improve the long-term survival of patients with radically
      resected positive nodes, and primary chemotherapy can make resectable
      approximately 50% of cases with fixed inguinal metastases. However, chemotherapy
      alone is not curative for metastatic disease.

PMID- 9266226
TI  - The value of tumor markers in testicular seminomas. Results of a prospective
      multicenter study.
AB  - OBJECTIVES: In the course of a prospective multicenter trial, the value of tumor
      markers in seminomas was assessed. METHODS: Human chorionic gonadotropin (HCG),
      lactate dehydrogenase (LDH) and placental alkaline phosphatase (PlAP) were
      determined before and after orchidectomy and in the follow-up. Patients with
      elevated alpha-fetoprotein were considered to have nonseminomas. The half-lives
      were 24-36 h for HCG and 1 day for LDH and PlAP. RESULTS: The incidence of HCG,
      LDH and PlAP was 35, 34 and 56%, respectively. In 84% of the patients at least
      one of the three markers was elevated. PlAP had the highest sensitivity to detect
      metastatic disease (51%), with a specificity of 91%. HCG and LDH were elevated in
      42 and 46% of patients in stage II-III with specificities of 95 and 96%. PlAP was
      the best method to indicate a relapse, but the specificity was low, especially in
      smokers. For nonsmokers it was in the same range as HCG and LDH. CONCLUSIONS:
      Eighty-four percent of seminomas are marker-positive. PlAP has the highest
      incidence and sensitivity. Specificity is impaired in smokers. All three markers
      should be determined in seminomas.

PMID- 9266228
TI  - Symptomatic outcome following clam ileocystoplasty.
AB  - OBJECTIVE: This study was designed to assess the outcome of clam ileocystoplasty
      (CI) based on patients' subjective perception and objectively validated scoring
      systems. Quality-of-life parameters were also examined as aspects of outcome.
      MATERIAL AND METHODS: Between 1989 and 1994, 27 patients (15 male and 12 female)
      underwent CI. The median age was 41 years (13-75 years). CI was performed after
      failed pharmacological treatment. The mean length of follow-up for this patient
      cohort was 18 months (range: 1-4 years). RESULTS: Overall cure rate was
      objectively assessed at 61%. Seventy-two percent of patients described a
      subjective improvement of symptoms, and a small number of patients (12.5%) were
      subjectively worse following the operation. Quality of life was improved in 75%
      of patients, with 12.5% showing no improvement and 12.5% being worse. Fifty-six
      percent of patients noted a minor degree of voiding dysfunction, whereas 25%
      noted moderate and 19% noted severe voiding dysfunction. CONCLUSIONS: CI offered
      improvement with satisfaction in the group of patients studied, however not all
      patients achieved a satisfactory outcome. The patients who were worse following
      the procedure were all young females with detrusor instability. Careful patient
      selection and pre-operative counselling may reduce the failure rate. Outcome
      analysis based on standardised questionnaires allows patients and surgeons to
      make informed decisions with realistic expectations.

PMID- 9266227
TI  - Quality of life and health in patients with urinary diversion: a comparison of
      incontinent versus continent urinary diversion.
AB  - OBJECTIVE: To compare the quality of life and health in patients with incontinent
      and continent urinary diversions, in correlation with the initial diagnosis,
      diversion-related symptoms, psychological status and employment status. MATERIALS
      AND METHODS: 81 patients (64% male and 36% female) with a mean age of 55 years
      (18-65 years) were included in this retrospective study. A total of 27 had an
      incontinent urinary diversion (group A) and 54 a continent diversion (group B).
      The initial diagnosis was malignant tumor in 75% (n = 61) and nontumor disease in
      25% (n = 20). A structured interview and psychometric instrument assessment of
      the quality of life as well as somatic and psychological symptoms were carried
      out and analyzed. RESULTS: Patients with nontumor disease, a continent reservoir
      and employment tended to have the highest level of quality of life. The higher
      the number and severity of psychological symptoms, such as depression and
      anxiety, the lower the level of global satisfaction with life, health and urinary
      diversion, and vice versa. No difference was seen between groups A and B
      concerning diversion-related symptoms, global satisfaction with life and health
      and sociodemographic data. CONCLUSIONS: The decision for a continent versus an
      incontinent urinary diversion must consider not only the medical factors of each
      individual patient, but also the initial diagnosis, psychological condition and
      employment status.

PMID- 9266229
TI  - The use of a simple home flow test as a quality indicator for male patients
      treated for lower urinary tract symptoms suggestive of bladder outlet
      obstruction.
AB  - OBJECTIVE: To evaluate the performance of a simple home flow test (HFT) in the
      examination and follow-up of patients suffering from lower urinary tract symptoms
      suggestive of bladder outlet obstruction. METHODS: One hundred seventy-two
      patients who were treated with either transurethral resection of the prostate or
      transurethral microwave therapy were included. Symptom evaluation, HFT and
      uroflowmetry were done before and 3 months following treatment. The patients'
      opinions about the need for further therapy and the effect of therapy were
      categorised at the follow-up. RESULTS: The HFT correlated strongly with the
      maximum flow rate (Qmax) both before and after therapy and it was better
      correlated to the symptoms of the patients and to the subjective effect of
      therapy compared to the Qmax. CONCLUSION: HFT is a cost-saving diagnostic
      technique for the classification of urinary flow and should be useful as a
      quality indicator in large-scale health care management programs.

PMID- 9266230
TI  - Urodynamic effects of doxazosin in men with lower urinary tract symptoms and
      benign prostatic obstruction. Results from three double-blind placebo-controlled
      studies.
AB  - OBJECTIVES: Urodynamic investigations provide an objective, quantitative
      evaluation of urinary function in patients with benign prostatic obstruction
      (BPO). The effects of doxazosin, a selective alpha 1-adrenoceptor antagonist, on
      urodynamic measurements were investigated in three double-blind, placebo
      controlled clinical studies of the treatment of BPO. METHODS: 302 normotensive
      and mildly hypertensive men with BPO were evaluated. Patients were randomized to
      receive doxazosin (1-4 mg o.d.) or placebo for 4-29 weeks. RESULTS: Doxazosin
      significantly improved free urinary flow rates compared with placebo. Urodynamic
      studies confirmed that doxazosin was effective in improving urinary flow, and
      also showed a reduction in detrusor pressure, resulting in decreased voiding time
      and increased voided volume. Analysis of pressure-flow data demonstrated a
      significant reduction in a measure of urethral resistance in doxazosin-treated
      patients. CONCLUSION: These results indicate that doxazosin is an important
      treatment option for patients with troublesome lower urinary tract symptoms and
      BPO.

PMID- 9266231
TI  - Effects of short-term treatment with the alpha 1-blocker alfuzosin on urodynamic
      pressure/flow parameters in patients with benign prostatic hyperplasia.
AB  - OBJECTIVE: The objective of this double-blind, placebo-controlled urodynamic
      pressure/flow study was to assess the efficacy of short-term treatment with the
      alpha 1-blocker alfuzosin in outflow obstruction of patients with symptomatic
      benign prostatic hyperplasia (BPH). MATERIAL AND METHODS: Urodynamic
      pressure/flow parameters were assessed after 2 weeks of placebo run-in, 4 weeks
      of placebo (47 patients) or 2.5 mg t.i.d. alfuzosin treatment (47 patients),
      followed by an 8-week extension period with alfuzosin (single-blind). RESULTS AND
      CONCLUSION: Four weeks of alfuzosin treatment significantly increased maximum
      flow (+29.0%) and decreased detrusor pressure at maximum flow (-30.2%), detrusor
      opening pressure (-39.4%) and maximum detrusor pressure (-28.7%). Short-term
      alfuzosin treatment improved outflow conditions in BPH by reducing prostatic
      urethral obstruction.

PMID- 9266232
TI  - Postejaculation serum prostate-specific antigen level.
AB  - OBJECTIVE: This study was carried out to determine whether ejaculation may modify
      the serum prostate-specific antigen (PSA) level and to investigate whether
      postejaculation serum PSA may play a role in male hypofertility work-up. METHODS:
      Serum PSA concentration was determined before and 1 h after ejaculation in 18
      healthy men (group A) and in 16 men with male-factor infertility (group B). PSA
      change (delta) was recorded and analyzed. RESULTS: Postejaculation serum PSA
      differed significantly from basal levels (p = 0.0037 by the Wilcoxon signed rank
      test). Following ejaculation, a rise was noticed in 74% of subjects. The median
      relative change in PSA concentration was 54%. No difference in respect to mean,
      median and relative change was observed between study groups. In two cases (6%),
      PSA rose from normal level to more than 4 ng/ml. CONCLUSION: A significant
      postejaculation serum PSA elevation does occur, it is thus recommended that men
      abstain from ejaculation for 24 h prior to PSA sampling. Postejaculation PSA was
      not found to significantly correlate with hypofertility.

PMID- 9266233
TI  - Prognostic significance of prostate-specific antigen levels two months after
      hormonal manipulation of metastatic prostate cancer.
AB  - OBJECTIVE: To assess the prognostic significance of prostate-specific antigen
      (PSA) levels before and during therapy in patients with metastatic adenocarcinoma
      of the prostate receiving hormonal manipulation. METHODS: The PSA levels before
      and during treatment, together with various clinicopathological parameters, were
      measured retrospectively in 48 patients with newly diagnosed metastatic prostate
      cancer. The prognostic importance of these measurements was analyzed by both
      univariate and multivariate techniques. RESULTS: PSA levels 2 months after
      treatment were the most useful predictors of progression-free (p = 0.004) or
      cause-specific survival (p = 0.006) in a multivariate Cox proportional-hazard
      model including histologic grade, age, performance status and pretreatment
      hemoglobin. CONCLUSIONS: We have found that a low PSA level 2 months after
      treatment is prognostically superior to conventional clinicopathological
      parameters, such as histologic grade, in patients with metastatic prostate cancer
      undergoing treatment by hormonal manipulation.

PMID- 9266234
TI  - Serum free/total prostatic-specific antigen in prostate cancer patients treated
      with LH-RH agonists.
AB  - OBJECTIVE: This study is based on promising results using the ratio of free/
      total (F/T) prostatic-specific antigen (PSA) for discrimination between benign
      prostatic hypertrophy and prostate cancer. We tried to determine the value of F/T
      PSA in different clinical situations at a certain time point during follow-up of
      luteinizing-hormone-releasing hormone (LH-RH) agonist treatment and to correlate
      it to T-PSA. PATIENTS AND METHODS: 182 patients followed-up for different periods
      in the last 3 years were routinely monitored for serum T-PSA. During the last 11
      months, F-PSA was also measured together with T-PSA, and the ratio of F/T PSA was
      calculated. In 26 patients, the ratio of F/T PSA was monitored sequentially in
      several samples. RESULTS: Although 5 patterns of clinical response to LH-RH
      agonists were identified according to previous T-PSA, the F/T ratio could
      significantly (p < 0.05) discriminate between patients responding to treatment in
      contrast to patients escaping, fluctuating or not responding to hormonal
      ablation. Those patients responding to hormones showed a higher F/T PSA ratio
      (36.5 +/- 33.1%) compared to the nonresponding group (12.0 +/- 10.1%).
      CONCLUSIONS: During individual follow-ups, the pattern of response to LH-RH
      treatment is reflected by the F/T PSA ratio: while successful treatment causes an
      F/T PSA increase, relapse is accompanied by a decrease in this ratio. However,
      the changes in the F/T PSA ratio did not precede the indicative changes in T-PSA.
      It seems that increased values of F/T PSA ratios are intrinsic features of
      'benign' prostatic disease, and the molecular events resulting in different PSA
      molecules in various clinical situations have to be elucidated.

PMID- 9266235
TI  - Value of the preoperative detection of prostate-specific-antigen-positive
      circulating cells by nested RT-PCR in patients submitted to radical
      prostatectomy.
AB  - OBJECTIVE: To assess the value of the detection of circulating prostate cells
      [prostate-specific antigen (PSA) positive] by reverse-transcriptase nested
      polymerase chain reaction (nested RT-PCR) to improve the staging of clinically
      localized prostate cancer. METHODS: Nested PCR was performed on blood samples of
      29 patients submitted to radical prostatectomy for clinically localized (T1-T2)
      prostate cancer. Nine patients with various benign urologic diseases comprised
      the negative control group. Incubation was for 25 cycles for each PCR, using beta
      2-microglobulin to test the integrity of RNA samples. Each sample was tested in
      quadruplicate and analyzed by agarose gel electrophoresis, blotted and hybridized
      with specific internal primers. Nested PCR results were compared with the pT
      stage of the prostate specimen, processed according to the Stanford method.
      RESULTS: In 6 out of 29 patients (20.7%) with clinically localized prostate
      cancer, circulating prostate cells were detected by nested PCR. There was no
      relationship between pathologic stage and RT-PCR results. Eleven out of 14 pT2
      patients (78.6%) were PCR negative and only 3 out of 15 pT3 patients (20%) were
      PCR positive. All control samples were PCR negative. CONCLUSIONS: In selected
      patients with T1-T2 prostate cancer, there was no relationship between pathologic
      stage and the presence of circulating PSA-positive cells detected by nested PCR.
      However, in 20.7% of patients with clinically localized prostate cancer,
      circulating prostate cancer cells were detected. A further follow-up based on PSA
      is necessary to clarify the clinical relevance of this biologic anomaly.

PMID- 9266236
TI  - Role of laparoscopic surgery in pediatric urology.
AB  - OBJECTIVES: In our clinic, laparoscopy was introduced in 1987 for the exploration
      of non-palpable testes and since 1991 it has also been applied with therapeutic
      aims. We present our experience with this minimally invasive technique in
      pediatric patients. PATIENTS AND METHODS: Between May 1987 and September 1996,
      219 laparoscopic procedures were performed in children. All children received
      general anesthesia. Positioning of the patient on a rotatable and tiltable
      operating table is very important. RESULTS: All laparoscopic interventions were
      well tolerated in children. The operative time for exploration of a nonpalpable
      testis ranged from 10 to 30 min, and for varix ligation from 15 to 30 min. In
      nephrectomy and nephroureterectomy cases 80-150 min were required. The excision
      of the urachal remnant and the drainage of lymphocele took between 30 and 70 min.
      No immediate postoperative complications were observed. Mobilization and oral
      intake were routinely carried out on the day of surgery. The children required
      little or no postoperative pain medication. CONCLUSION: Laparoscopy has been
      found to be the most reliable diagnostic tool in evaluating nonpalpable testes
      within the pediatric population. This approach enables subsequent therapy of
      laparoscopic orchiectomy, primary laparoendoscopic orchidopexy, or
      laparoscopically assisted two-stage Fowler-Stephens maneuver. Laparoscopic varix
      ligation is a simple and highly effective treatment modality for the pubescent
      male with a symptomatic varicocele. To date, the recurrence rate is 1.8% based on
      80 patients followed for over 1 year. Fenestration of lymphoceles following renal
      transplantation has been found to be as efficaciously treated with laparoscopy as
      with open surgery. Laparoscopic nephrectomy and/or nephroureterectomy are
      technically demanding procedures and should only be performed by an experienced
      laparoscopic surgical team to minimize the complication rate. At the present
      time, the intraoperative costs of laparoscopic surgery are greater than with open
      surgery due to the use of disposable instrumentation and longer operating room
      times. However, minimally invasive surgery continues to gain a greater and more
      important role in the field of pediatric urology.

PMID- 9266237
TI  - Renal functions of enuretic and nonenuretic children: hypernatriuria and
      kaliuresis as causes of nocturnal enuresis.
AB  - OBJECTIVE: The aim of this study was to investigate the pathophysiologic cause(s)
      of primary nocturnal enuresis. Therefore, electrolyte concentrations of urine
      specimens were evaluated in the morning, and alterations compared between
      enuretics and nonenuretics. METHODS AND PATIENTS: First morning urine specimens
      of 27 enuretics and 21 nonenuretic subjects fed the same diet were collected, and
      urinary electrolytes were measured. The urinary Ca/Cr ratio, tubular reabsorption
      of phosphorus (TRP) and fractional sodium (FE Na%) and potassium excretions (FE
      K%) were determined for patients and controls. RESULTS: There was no significant
      difference in the Ca/Cr ratio and TRP between patients and controls, but enuretic
      patients had significantly higher FE Na% and FE K% values than controls (p <
      0.001). There were significant positive correlations between FE Na% and (r =
      0.81, p < 0.001) FE K% and the frequency of bedwetting, respectively, among
      enuretic patients (r = 0.54, p < 0.001). CONCLUSION: Since Na and K excretion of
      enuretic patients was higher than in nonenuretics, it can be concluded that there
      may be a benign hereditary and/or postural renal tubular handling disorder of Na
      and K in enuretic children.

PMID- 9266238
TI  - Influence of high-intensity focused ultrasound on the development of metastases.
AB  - OBJECTIVE: The hypothesis that exposure of a solid tumor to high-intensity
      focused ultrasound (HIFU) could lead to an increase of metastases was
      investigated in an animal model. METHODS: The highly metastatic AT-6 Dunning
      R3327 rat prostate cancer subline was implanted into the hind limb of Fisher
      Copenhagen rats and was exposed to 1 pulse/mm2 tumor (acoustical power 1,000
      W/cm2) delivered by an experimental machine (Ablatherm, Technomed, France), or
      the animals were sham treated, as soon as the tumor had reached a volume of 175
      225 mm3. The tumor-bearing leg was amputated 24 h later and the number of
      metastases examined 12 weeks thereafter at autopsy. RESULTS: Metastases were seen
      in 3 (23%) of the 13 animals exposed to HIFU and in 4 (25%) of the 16 sham
      treated animals; this is not significantly different. There was also no
      significant difference in weight of the lungs that contained metastases between
      sham-treated and HIFU-treated animals. CONCLUSION: Metastatic spread of animal
      tumors with a high metastatic potential is not enhanced by HIFU exposure.

PMID- 9266239
TI  - Relationship between DNA ploidy and functional estrogen receptors in operable
      prostate cancer.
AB  - OBJECTIVE: To evaluate the relationship between the nuclear DNA content and the
      tissue estrogen receptor (ER) level in patients with operable adenocarcinoma of
      the prostate. METHOD: Surgical specimens taken from 73 patients with clinically
      localized prostate cancer were studied. Tumor DNA ploidy pattern as measured by
      flow cytometry was correlated with the level of functional ER using the nuclear
      biopsy assay. RESULTS: Forty-five percent of the tumors were DNA diploid, and 55%
      had an abnormal ploidy pattern (DNA tetraploid or DNA aneuploid). The ER level
      ranged from 0 to 6,475 fmol/mg DNA (mean 839 fmol/mg DNA). Twenty-two percent had
      no functional receptors. Marked association was noted between ER and nuclear DNA
      content. Seventy-five percent of the tumors with no ER had abnormal ploidy
      patterns. The mean receptor level for DNA diploid prostate cancer was 1,034
      fmol/mg DNA versus 661 fmol/mg DNA for DNA nondiploid tumors (p < 0.008). An
      inverse correlation was found between ER values and histologic grade or
      pathologic stage. High-grade and high-stage tumors had lower levels of ER
      compared to low-grade and early-stage carcinomas. CONCLUSION: Our results
      demonstrate an association between ER values and variables that predict prognosis
      in prostate cancer. It is possible that this parameter may be helpful in
      identification of prognostic groups in patients with prostate cancer.

PMID- 9266240
TI  - Localization of NADPH diaphorase and vasoactive intestinal polypeptide-containing
      neurons in the efferent pathway to the rat corpus cavernosum.
AB  - OBJECTIVE: We examined the coexistence of nitric oxide synthase (NOS) and
      vasoactive intestinal peptide (VIP) in the efferent pathway to the rat corpus
      cavernosum. METHODS: We used NADPH diaphorase (ND) histochemical staining, a
      specific marker of neuronal NOS, in combination with retrograde axonal transport
      of True Blue (TB) and VIP immunohistochemistry. RESULTS: Many neurons were
      labeled by TB in the cavernous nerve and the body of the major pelvic ganglion
      (MPG), and fewer neurons in the pelvic nerve. In the cavernous nerve, about 90%
      of TB-labeled efferent neurons were ND positive, and about 80% in the body of the
      MPG and pelvic nerve. Besides, 60-80% of TB-labeled efferent neurons projecting
      to the corpus cavernosum showed VIP immunoreactivity. VIP was colocalized with
      NOS in 70-80% of neurons. CONCLUSIONS: These findings suggest that most of the ND
      positive nerves and terminals in the corpus cavernosum come from the MPG via the
      cavernous nerve and that NO plays an important role; it may act in combination
      with NO because most NOS-containing neurons simultaneously showed VIP
      immunoreactivity.

PMID- 9266241
TI  - Olfactory-corporeal reflex: description of a new reflex and its role in the
      erectile process.
AB  - OBJECTIVE: The dog approaches the bitch and smells the vulva. The relationship
      which seems to exist between a special smell in the bitch and sexual arousal in
      the male dog was investigated. METHODS: 12 male dogs and 25 bitches were studied.
      The bitches were divided into five equal groups, each representing 1 of the 5
      phases of the estrous cycle. A vaginal swab that soaked in the bitches' vaginal
      secretions was divided into two pieces: one was sent for estradiol and
      progesterone determination, and the other was smelt by the male dog. The
      responses of the intracorporeal pressure (IP) and the electromyographic activity
      of the bulbo- and ischiocavernosus (BC, IC) muscles of the male dog to the
      smelling of bitch's vaginal odor were assessed. The pressure response was also
      determined 10 min and 1 h after either the nasal mucosa or the corporeal tissue
      was anesthetized. RESULTS: Elevated IP was recorded in 12 of 12, 10 of 12 and 8
      of 12 dogs smelling vaginal swabs of bitches in metestrus (p < 0.001), estrus (p
      < 0.001), and diestrus (p < 0.01), respectively. No pressure response occurred
      when the vaginal swab was smelt while the nasal mucosa or the corporeal tissue
      was anesthetized. The BC and IC muscles exhibited no response to smelling of the
      vaginal swab of bitches in any phase of the estrous cycle. The results were
      reproducible. CONCLUSIONS: The study showed that the IP increased with smelling
      of vaginal secretions containing high progesterone levels, whereas estradiol-17
      beta did not effect IP elevations. The higher the progesterone level, the greater
      the IP. The increased IP is not due to BC and IC muscle contraction. It is
      postulated that a reflex relationship exists between IP elevation and olfactory
      stimulation. This reflex response was reproducible and was not evoked when the
      two arms of the reflex were anesthetized. We call this reflex 'olfactory
      corporeal reflex'. This reflex seems to prime the male dog for sexual
      intercourse.

PMID- 9266242
TI  - Value of p53 expression, cellular proliferation, and DNA content as prognostic
      indicators in renal cell carcinoma.
AB  - OBJECTIVE: In renal cell carcinoma (RCC) little is known about the basic
      mechanisms of cell proliferation and differentiation leading to growth, invasion,
      and eventual metastasis. In the present study, the prognostic significance of
      proliferative activity, p53 activity, and ploidy is analyzed. METHODS: In 90
      patients with RCC overexpression of the p53 protein. DNA ploidy and proliferation
      status as determined by the monoclonal antibodies Ki-67 and Ki-S5 were analyzed
      in addition to tumor malignancy grade and stage and correlated with the clinical
      course. RESULTS: During the follow-up period (average 38 months) 23% of the
      patients had a progressive course. Only the Ki-S5 index correlated with stage,
      grade, and clinical course. Ploidy, p53, and Ki-67 correlated neither with tumor
      stage and grade nor with the clinical course. CONCLUSION: The proliferation
      activity determined with the monoclonal antibody Ki-S5 represents the most
      promising prognostic factor of the pathological indicators considered for the
      clinical course of RCC.

PMID- 9266243
TI  - Seizures associated with cisplatin administration.
AB  - A 50-year-old patient with a diagnosis of a primary extragonadal germ cell tumor
      received cisplatin-containing polychemotherapy and developed seizures after the
      first course of drug administration. We discuss this very rare toxic side effect
      of cisplatin and present a review of the literature concerning the experience
      with neurotoxic effects exerted by this agent.

PMID- 9266244
TI  - Benign schwannoma surrounding and obstructing the ureteropelvic junction. First
      case report.
AB  - With a varied presentation and a difficult preoperative diagnosis, schwannoma
      accounts for only a small percentage of retroperitoneal tumors. Moreover,
      malignant schwannoma of the adrenal gland, kidney and renal pelvis has previously
      been described. We report the first case of benign schwannoma causing obstruction
      by external compression of the ureteropelvic junction. A case report of a male
      patient who complained of a 3-month history of dull lumbar pain on the right side
      is reported. Using intravenous pyelogram, sonography and computed tomography a
      benign tumor of the retroperitoneum was suspected. Upon exploration, the
      suspected diagnosis of the tumor's retroperitoneal origin was confirmed. After
      the histological and immunohistochemical studies the diagnosis was verified. The
      diagnosis, treatment and histological features of benign schwannoma are
      discussed. A brief review of the literature is also included.

PMID- 9266245
TI  - Giovanni Domenico Santorini (1681-1737) Charles-Pierre Denonvilliers (1808-1872).
      First description of urosurgically relevant structures in the small pelvis.

PMID- 9266246
TI  - [Motor dysfunction in the aged--approach to involuntary movements].
AB  - The clinical, pathophysiological and therapeutic approaches to the representative
      involuntary movements encountered in the aged are described. The prevalence rates
      of Parkinson disease and essential tremor are very high, and their diagnoses and
      treatments are quite important. Recent advances in treating Parkinson disease
      with anti-parkinsonian medications and essential tremor with beta-adrenergic
      blockers were presented. Blepharospasms, though uncommon, but occasionally seen
      in the aged persons, are disabled conditions. The botulinus toxin injections to
      the orbicularis oculi muscles proved to show dramatic therapeutic effects,
      greatly contributing to these patients' ADL. The importance of neuroscience in
      the coming 21st century is also stressed.

PMID- 9266247
TI  - [Cervico-omo-brachial pain and disability in a person of advanced age].
AB  - A person of advanced age usually has degenerative changes of bone, joint and
      ligament, which can be causes of cervico-omo-brachial pain and disability. He or
      she may also suffer from metastatic bone tumor of cervical spine or upper
      extremity. This article described pathology, signs and symptoms and recent
      treatment of these diseases. Cervical myelopathy and radiculopathy, which are
      most common causes of cervico-omo-brachial symptoms, are sometimes accompanied by
      peripheral entrapment neuropathy such as cubital tunnel syndrome or carpal tunnel
      syndrome (double crush syndrome). In this complicated situation, decompression of
      neural tissue in both cervical spine and carpal tunnel are necessary. In
      treatment for carpal tunnel syndrome, release of transverse carpal ligament under
      an arthroscope has proven to be useful and has been becoming popular. This
      minimally invasive surgery is also useful in shoulder surgery such as subacromial
      decompression in aged patients with rotator cuff tear and removal of calcium
      deposit in the shoulder joint. Osteoarthritis of the elbow also cause pain or
      disability of the elbow and the hand. Some metastatic bone tumors are treated by
      tumor resection and reconstruction with instruments, prosthesis or composite
      grafts, which are attempted not to cure the disease but to maintain or improve
      the quality of life of the patient.

PMID- 9266249
TI  - [Geriatric femoral neck fractures--how to regain prefracture ambulatory status].
AB  - The incidence of hip fractures increases with increasing age. And mortality rate
      in elderly patients of hip fractures are high and which is reported to be up to
      30% within 1 year following fractures. Prosthetic replacements for femoral neck
      fractures and internal fixations using solid fixation devices for
      intertrochanteric fractures are recommended for these elderly patients for
      regaining preinjury level of ambulation and good and reasonable quality of their
      lives.

PMID- 9266248
TI  - [Knee pain in the aged--pathomechanism, diagnosis, and treatment of
      osteoarthritis of the knee].
AB  - Osteoarthritis is the most common cause of knee pain in the aged. This disease is
      characterized by degenerative changes in the articular cartilage and subsequent
      new bone formation at the articular margins. The primary defect in hyaline
      cartilage is an alteration in the ratio of total glycosaminoglycans to that of
      the collagen fiber content in the matrix. The disease frequently is primary but
      various predisposing conditions are recognized. In early phase of this disease,
      the patient complains of pain, which appears with exercise but can be "walked
      off". The joint is often felt to creak and grate, and swells from time to time,
      especially after any unusual activity involving a flexed position. As the disease
      progresses, the patient finds increasing difficulty in the activities of daily
      life. It should be emphasized that, in the early phase, almost of all patients
      can be managed by conservative means such as weight loss, isometric quadriceps
      exercises, use of a walking stick and antiinflammatory analgesic drugs. The
      predominant indication for surgical treatment is persistent pain and serious
      disturbance of the activities of daily life against conservative treatment. High
      tibial osteotomy has proved to be useful in the medial osteoarthritic knees.
      However, the long-term follow-up studies conducted by the author have shown that
      effects of this procedure gradually deteriorate after 10 years. Clinical results
      of total prosthetic replacement of the knee joint have been well improved in this
      decade. Ten-year survivorship has recently been reported to be 95% or more.
      However, the most common problem is loosening of the component. Wear particles
      derived from the tibial plate made from ultra high molecular weight polyethylene
      have been noted as the primary cause of the loosening.

PMID- 9266250
TI  - [Back pain and neurological deficits in osteoporotic spinal fractures].
AB  - Generally osteoporotic compression fractures of the spine cause only localized
      pain and kyphosis without other significant complications. These fractures
      usually heal without difficulty by conservative treatment. However, it becomes to
      be accepted as a general concept that a small number of patients with
      osteoporotic fracture of the thoracolumbar spine result in delayed vertebral body
      collapse with neural compromise. We analyzed our series of osteoporotic
      posttraumatic vertebral collapse. We had treated 51 consecutive patients with
      posttraumatic vertebral collapse following osteoporotic compression fractures of
      the thoracolumbar spine between Jan. 1987 and June 1994. Surgery consisted of
      anterior spinal reconstruction by strut grafting using a bioactive ceramic
      vertebral prosthesis (A-WGC) and autogenous rib in combination with the Kaneda
      device after resecting the collapsed vertebral bodies. After surgery, 80% of the
      patients with initial neurological deficits showed remarkable neurological
      recovery. The causes of neural compression were retropulsion of the posterior
      part of the collapsed vertebral body into the spinal canal and unstable kyphosis.
      The collapsed portion of the resected vertebral bodies was always less bloody or
      ischemic. Histology confirmed ischemic necrosis of the collapsed portion. The
      collapse would be resulted in by the compromised healing process due to repeated
      micro-traumas to the fragile trabecular bone following osteoporotic vertebral
      fracture. Autogenous iliac bone as well as fibula cannot be used as another
      alternative strut graft because of the fragility of the graft and grafted site.
      The anterior reconstruction with a bioactive ceramic vertebral prosthesis and the
      Kaneda device has been useful in osteonecrotic-posttraumatic vertebral collapse
      of the thoracolumbar spine.

PMID- 9266251
TI  - [Rehabilitation for musculoskeltal disorders in geriatric patients].
AB  - Aging is typically accompanied by gradual but progressive physiological changes
      and an increased prevalence of acute and chronic illness in any organs.
      Musculoskeltal system is one of the most involved organs in geriatric patients.
      Appropriate roles in geriatric rehabilitation for musculoskeltal disorders should
      be emphasized not only to treat the disorders, but also to prevent many
      complications cause by specific disease or injury. Representative management
      methods in geriatric rehabilitation are introduced in this section. Rest is often
      effective, especially in the acute phase of illness or injury. However, cautions
      should be paid in disuse syndrome which may be produced by prolonged bed rest.
      Major manifestations in this syndrome includes muscle weakness and atrophy, joint
      contracture, decubitus, osteoporosis, ectopic ossification, cardiovascular
      impairment, pneumonia, urological and mental problems. Physical agents such as
      heat, cold, light and pressure have been used as therapeutic agents. Electrical
      stimulation is often effective in the treatment of low-back pain syndrome.
      Traction is the act of drawing, or a pulling force. Its mechanism to relieve pain
      seems to immobilize the injured parts, to increase peripheral circulation by
      massage effect and to improve muscle spasm. Brace is very effective to control
      acute pain in musculoskeltal system. However, long-term wear of brace should be
      avoided to prevent the disuse syndrome. Exercise is one of the most important
      rehabilitation modalities. This includes stretching and muscle strengthening
      programs. Education of body mechanism in activity of daily living is essential in
      rehabilitation of geriatric patients.

PMID- 9266252
TI  - [Studies on Fas ligand expression in patients with systemic lupus erythematosus].
AB  - The Fas/Fas ligand (FasL)-mediated apoptosis may play a role in the induction and
      maintenance of T cell tolerance. To investigate the role of FasL in the apoptosis
      of lymphocytes in autoimmune diseases, gene and protein expression of FasL were
      examined in peripheral blood mononuclear cells (PBMC) from patients with systemic
      lupus erythematosus (SLE) or rheumatoid arthritis (RA), and from healthy donors
      by a newly-designed semiquantitative reverse transcription (RT)-PCR and flow
      cytometry. Although no significant difference in FasL gene expression was
      obtained among three groups, SLE patients exhibited a wide distribution of the
      values. In SLE patients, there was a significant correlation between FasL gene
      expression by PBMC and some clinical parameters including SLE Disease Activity
      Index (SLEDAI) score, anti-DNA antibody titer and complement titer (CH50). More
      interestingly, a marked increase in FasL gene expression was observed in
      untreated SLE patients, whereas a significant decrease was observed in
      prednisolone-treated SLE patients. Flow cytometric analysis revealed the
      expression of FasL on T cell subsets from SLE patients and on anti-CD3 mAb
      stimulated T cells from healthy donors. In vitro experiments, dexamethasone
      inhibited FasL gene expression by PBMC from healthy donors in a dose-dependent
      manner and with time of incubation. These results clearly indicate that FasL is
      up-regulated in active SLE patients, reflecting in vivo T cell activation, and
      that corticosteroids directly down-regulate FasL gene expression by human PBMC.

PMID- 9266253
TI  - [Inhibition of EGF and TGF-beta dependent transformation of NRK23 cells by Crk II
      23 mutant].
AB  - Adaptor proteins participate in many signaling pathways from cell surface
      receptors. Crk protein was the first example of the adaptor protein. We have
      examined the function of Crk II mutant, Crk II-23. The Crk II-23 mutant contains
      two amino-acid substitutions in the carboxyl-terminal SH3 domain and is known to
      inhibit the transformation of NRK cells induced by epidermal growth factor (EGF)
      and transforming growth factor-beta (TGF-beta). There was no remarkable
      difference between Crk II and Crk II-23 in EGF-dependent binding to EGF receptor
      (EGFR). However, in contrast to the wild-type Crk II, the Crk II-23 mutant bound
      to EGFR in quiescent NIH 3T3 cells. To clarify the difference, both the Crk II
      and Crk II-23, proteins were expressed in E. coli and examined their binding
      capacity in vitro. They bound to EGFR from EGF-stimulated NIH 3T3 cells in vitro
      to a similar extent. Expression of Crk II-23 in NIH 3T3 cells did not affect the
      binding of bacterially expressed Crk II and Crk II-23 to EGFR. These results
      suggest that post-translational modification of Crk II-23, such as physical
      association to cellular proteins, induces binding of Crk II-23 to EGFR in
      quiescent cells. We also demonstrated that mutation of either the SH2 or the SH3
      domain abolished the anti-oncogenic activity of Crk II-23, although both mutants
      bound to EGFR in the quiescent cells. From these results, it could be concluded
      that persistent signaling through Crk II-23 bound to EGFR is responsible for the
      suppression of transformation by EGF and TGF-beta.

PMID- 9266254
TI  - Ecological aspects of antimicrobial treatment of Helicobacter pylori infections.

PMID- 9266255
TI  - Chemoprophylaxis of group B streptococcal infections.

PMID- 9266257
TI  - Prevalence of nosocomial infections--who knows the true rates?

PMID- 9266256
TI  - Nosocomial and community-acquired infections in Germany. Summary of the results
      of the First National Prevalence Study (NIDEP)
AB  - The first German national study on the prevalence of nosocomial and community
      acquired infections was performed in 1994 in medical, surgical,
      gynaecological/obstetrical and intensive care departments. 14,966 patients in 72
      German hospitals representatively selected according to size were investigated by
      outside physicians. These were trained in the use of CDC definitions for
      nosocomial infections, and their diagnoses validated. Community-acquired
      infections were recorded according to the assessment of the hospital physicians.
      For the diagnosis of nosocomial infections, only the opinion of the outside
      investigators was decisive. A prevalence of 3.5% was found for nosocomial
      infections and 10.0% for community-acquired infections. The use of antibiotics
      was documented in 17.7% of all patients on the prevalence day. Of the patients
      undergoing antibiotic therapy, 16.9% had a nosocomial infection, 47.9% a
      community-acquired one. In the remaining 35.1% neither a nosocomial nor a
      community-acquired infection was confirmed.

PMID- 9266259
TI  - Granulocyte colony-stimulating factor (G-CSF) serum levels in surgical intensive
      care patients.
AB  - The granulocyte colony-stimulating factor (G-CSF) regulates neutrophil
      differentiation and function. Serum levels of G-CSF increase during acute
      infectious processes. The levels of G-CSF were measured in 59 surgical intensive
      care unit (ICU) patients. In general, G-CSF was only elevated during the first 2
      days after admission to the ICU. Higher G-CSF levels were more frequently
      observed in patients without infectious complications and in patients who
      survived. Later on, G-CSF levels were below 100 pg/ml in almost all patients
      studied. The highest G-CSF level (20,000 pg/ml) was observed in one patient with
      septic shock 36 h after leukopenia. The patient recovered from septic shock and
      multiple organ failure and was discharged. It is proposed that surgical ICU
      patients with low or undetectable G-CSF serum levels may benefit from exogenous G
      CSF substitution protocols.

PMID- 9266258
TI  - Differential cytokine production in stimulated blood cultures from intensive care
      patients with bacterial infections.
AB  - Mice infected with bacteria develop an interferon-gamma (IFN-gamma) dependent
      hypersensitivity to lipopolysaccharide (LPS) and other bacterial components. The
      broader aim of this study is to find out whether such hypersensitivity also
      occurs in patients suffering from bacterial infections. The capacity of
      stimulated peripheral blood cells from infected, intensive-care patients to
      produce cytokines (IFN-gamma, tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6)) was compared to that of healthy donors. Culturing of the
      cells was carried out preferentially in whole blood diluted 1:3. Whole blood
      cultures (WBC) were stimulated with lipopolysaccharide (LPS), whole killed
      Salmonella typhimurium and Staphylococcus aureus and concanavalin A (ConA), and
      the cytokine production was determined. Two main findings emerged from this
      study: The IFN-gamma production by WBC of patients was, compared to healthy
      donors, markedly suppressed, regardless of stimulus used. Further, patients' WBC
      exhibited a suppressed TNF-alpha production after stimulation with LPS.
      Surprisingly, following stimulation with bacteria (S. typhimurium and S. aureus)
      an elevated TNF-alpha and IL-6 response was obtained. Thus, in severely infected
      patients the cytokine responses of peripheral blood cells to LPS may be
      suppressed, while the response to other bacterial components is enhanced.

PMID- 9266260
TI  - Surgical site infection: rates, etiology and resistance patterns to
      antimicrobials among strains isolated at Rio de Janeiro University Hospital.
AB  - A 6-month prospective surveillance was conducted in the Department of General
      Surgery of the Rio de Janeiro University Hospital. Postoperative infections were
      classified according to CDC criteria. This study reports a significant rate
      (16.9%) in surgical infections detected by surveillance in a series where 45% of
      surgical interventions were classified as clean. The majority (52.7%) was
      apparent only after patient discharge from the hospital. Bacterial cultures were
      obtained from 42 out of 55 infected wounds. Staphylococcus aureus was the most
      frequently found pathogen (33.9%), followed by Escherichia coli (20.3%). With the
      exception of S. aureus isolates, multiresistance was found in 66% of coagulase
      negative staphylococci and 60% of gram-negative bacteria. This study showed that
      community surveillance associated with hospital surveillance is necessary in
      order to determine accurate rates of surgical site infections, and also showed
      that the emergence of multiresistant bacterial strains was common among isolates
      of surgical infections.

PMID- 9266261
TI  - Hydatid disease of the spine: a survey study from Turkey.
AB  - Spinal hydatid disease is rare, even in rural areas where echinococcosis is
      endemic. Although the liver and lungs are commonly involved, spinal hydatid
      disease, either primary or secondary, represents an uncommon but significant
      manifestation of the disease. This survey study reviews 28 reports of spinal
      hydatid disease from Turkey during the past 5 decades. Only 14 patients also had
      pulmonary or some other organ infestation. The cysts affecting the spine were
      commonly in the thoracic region. Most patients had intraspinal extradural hydatid
      cysts associated with vertebral involvement. The presenting symptoms were mostly
      atypical, and it was interesting that most of the patients were misdiagnosed
      preoperatively as Pott's disease during the first decades, suggesting that new
      imaging techniques such as CT and MRI are the diagnostic procedures of choice for
      this disease. Surgery remains the best therapy for spinal hydatid disease,
      although adjuvant antihelminthic therapy may be necessary. There were only 15
      cases of recurrence (18%); surgical intervention was palliative in all these
      patients and it was followed by chemotherapy. Operative mortality was very low
      (two patients died in the early postoperative period) and there were no
      complications related to treatment with antihelminthic drugs. The study indicates
      that hydatid disease should be considered in the differential diagnosis when
      radiological findings suggest spinal infections or tumors, and that surgical
      decompression in association with chemotherapy is the treatment of choice.

PMID- 9266262
TI  - Ciprofloxacin once daily versus twice daily for the treatment of pulmonary
      tuberculosis.
AB  - Ciprofloxacin was used as an antituberculous drug in adult patients who could not
      tolerate standard regimens or had to be treated with alternative combinations for
      resistance problems. During October 1986 to December 1991, 241 patients received
      ciprofloxacin in two daily 500 mg doses administered under supervision at 8.30
      a.m. and 5 p.m., respectively. This group of patients was submitted to
      retrospective analysis for tolerability and clinical as well as microbiological
      efficacy. In January 1992, a once daily regimen with 1,000 mg of ciprofloxacin
      was introduced in order to simplify drug administration together with the other
      combination partners and to take advantage of higher drug levels at the site of
      infection. These patients were followed prospectively for safety and efficacy.
      Until July 1993, 227 patients with smear-positive pulmonary tuberculosis were
      included in this open study. Comparative analysis was carried out for a selected
      group of patients who had remained smear and culture positive for more than 27
      days after start of treatment. Fifty-four patients who had received ciprofloxacin
      twice daily and 35 patients on the once daily regimen were evaluable. Both
      regimens were equally well tolerated. The once daily regimen was associated with
      a trend towards earlier conversion to smear negativity and a significantly
      shorter time to culture negativity. Smears became negative on average within 84
      days with the once daily and in 94 days with the twice daily schedule (p = 0.19).
      Culture negativity occurred at 60 and 76 days in the respective groups (p =
      0.0013; log Rank test). Of the patients who received ciprofloxacin twice daily,
      33% were still smear and culture positive 90 days after start of treatment
      compared to only 15% of the patients treated with the once daily schedule. We
      conclude that ciprofloxacin, given as a single daily dose of 1,000 mg is as safe
      as two 500 mg doses, more convenient to apply and probably more efficacious.

PMID- 9266263
TI  - Multiple intracranial tuberculomas with atypical response to tuberculostatic
      chemotherapy: literature review and a case report.
AB  - Approximately 34 cases of intracranial tuberculomas with paradoxical response to
      antituberculous chemotherapy have been documented worldwide. In most of the
      previously reported cases an associated tuberculous meningitis was reported. The
      majority of these patients were children or young adults, who had inoperable
      intracranial tuberculomas located in high risk regions that developed a few weeks
      or months after the start of an appropriate chemotherapy. Fifty-three percent of
      the patients recovered completely, 37% improved with mild neurological defects
      and 10% died. It is interesting that these intracranial tuberculomas developed or
      enlarged at a stage when systemic tuberculosis was being treated successfully. A
      recent experience with these potentially curable tumors of the central nervous
      system is reported. The literature is reviewed, and diagnostic and therapeutic
      considerations are discussed. The possible immunological mechanisms of this
      phenomenon are analyzed. In conclusion, patients who are suspected to have a CNS
      tuberculosis should receive a prolonged (12-30 months) course of effective
      antituberculous therapy. The evidence of new intracranial tuberculomas or the
      expansion of older existing lesions does not indicate the need to change the
      antituberculous drug program. In such cases systemic dexamethasone as adjuvant
      therapy for 4 to 8 weeks is worthwhile and effective. Surgical intervention may
      be necessary in situations with acute complications of CNS tuberculosis, such as
      shunting procedures for the treatment of hydrocephalus. When the diagnosis is not
      ensured and there is no response to therapy within 8 weeks, a stereotactic biopsy
      on a suspected tuberculoma could be performed. If the largest lesion is not
      located in high risk deep regions of the brain, it could be totally removed
      surgically. With this combined management, a satisfactory outcome can be obtained
      in the majority of cases.

PMID- 9266264
TI  - Transformation of cystic forms of Borrelia burgdorferi to normal, mobile
      spirochetes.
AB  - The purpose of this study was to evaluate the behaviour of Borrelia burgdorferi
      under controlled conditions. The occurrence of cystic forms of Borrelia
      burgdorferi in vitro was noted, and these cysts were able to be transformed to
      normal, mobile spirochetes. B. burgdorferi was cultivated in a commercial culture
      medium without serum. The spirochetes multiplied only slowly in this medium, and
      transformation to encysted forms was observed after 1 week. When these cysts were
      transferred to the same culture medium with rabbit serum, the encysted forms
      developed into regular, mobile spirochetes after 6 weeks, and their regeneration
      time was normal. Examination of these cysts in the transmission electron
      microscope revealed transverse fission inside the cysts. It is probable that
      similar phenomena may occur in vivo under conditions unfavourable for
      spirochetes. These observations may help to explain why diagnosis and treatment
      of B. burgdorferi infections in humans can be difficult.

PMID- 9266265
TI  - Culture and biological activity of Propionibacterium acnes.
AB  - Administration of killed Propionibacterium acnes to experimental animals leads to
      the development of hypersensitivity to the lethal and cytokine-inducing effects
      of endotoxin. This sensitizing property of P. acnes is not always expressed by
      different bacterial preparations. Its expression depends very much on the
      conditions employed for the cultivation of this microorganism. The present study
      investigates which culturing conditions result in P. acnes preparations with
      optimal sensitizing properties. The composition of the medium, the culturing time
      and temperature as well as the type of cultivation (in minifermentor or
      stationary culture) were all varied for this purpose. The resulting bacterial
      preparations were killed at 65 degrees C for 1 h and tested for sensitizing
      activity. The results show that stationary cultures of P. acnes grown at 37
      degrees C for 4 to 5 days in the appropriate medium produce biologically active
      preparations with satisfactory sensitizing activity.

PMID- 9266266
TI  - Analysis of a case of recurrent bacteraemia due to group A Streptococcus
      equisimilis by pulsed-field gel electrophoresis.
AB  - An 86-year-old woman with a history of metastatic breast cancer developed two
      episodes of streptococcal bacteraemia and erysipelas separated by an interval of
      3 months. The isolates belonged to Lancefield group A but were biochemically
      identified as Streptococcus equisimilis. The similarity of the two isolates was
      established by DNA macrorestriction analysis and pulsed-field gel
      electrophoresis, indicating that the second episode was due to relapse and not
      reinfection.

PMID- 9266267
TI  - Life-threatening infection with multiresistant Staphylococcus epidermidis in a
      patient with end-stage renal disease: cure with chloramphenicol and
      quinupristin/dalfopristin (RP 59500).
AB  - A 45-year-old man with end-stage renal disease underwent a cadaveric kidney
      transplantation. The allograft had to he removed 10 days after transplantation
      because of an acute vascular rejection. After explantation, the patient suffered
      from a life-threatening infection with Staphylococcus epidermidis involving
      lungs, eyes and liver for 11 months. Despite adequate therapy including
      vancomycin followed by teicoplanin, he developed spondylodiscitis requiring
      repeated surgical interventions. The definitive cure was achieved by a sequential
      therapy with chloramphenicol and quinupristin/dalfopristin.

PMID- 9266268
TI  - Effect of CMV serology and CMV disease on AIDS morbidity and mortality.

PMID- 9266269
TI  - Negative polymerase chain reaction in a child with tuberculous
      meningoencephalitis.

PMID- 9266270
TI  - Pharmacokinetics of ampicillin, sulbactam and cefotiam in patients undergoing
      orthopedic surgery.
AB  - As perioperative prophylaxis for major orthopedic operations 81 patients were
      given the fixed combination of ampicillin (1 g)/sulbactam (0.5 g) or cefotiam (2
      g) as short infusions. The three beta-lactams were rapidly distributed into the
      different tissues and their pharmacokinetic profiles were found to be very
      similar. It was noteworthy that ampicillin, sulbactam and cefotiam penetrated
      within minutes, not only into skin, fat and muscles, but also into bone. Thus
      0.25 h after starting the infusion the following mean concentrations were
      measured in bone: 21.8 +/- 10.5 mg/kg ampicillin, 4.9 +/- 2.2 mg/kg sulbactam and
      19.4 +/- 10.6 mg/kg cefotiam. For a period of at least 2 h the concentrations
      measured in serum and in the different tissues affected by the operation (skin,
      fat, muscle, bone) were above the MICs for pathogens which are involved in
      postoperative wound infections. On the basis of pharmacokinetic data,
      ampicillin/sulbactam and cefotiam seem about equally suitable for perioperative
      prophylaxis in major orthopedic operations.

PMID- 9266271
TI  - Inflammatory mechanisms in atherosclerosis, Glaxo-Wellcome Medicines Research
      Centre, Stevenage, Herts, UK, 3rd July 1995.

PMID- 9266272
TI  - Effects of tiaprofenic acid on urinary pyridinium crosslinks in adjuvant
      arthritic rats: comparison with doxycycline.
AB  - OBJECTIVE AND DESIGN: To study the effects of tiaprofenic acid and doxycycline on
      urinary pyridinium crosslinks and paw swelling in adjuvant arthritic rats, and to
      gain additional information on the drugs' inhibitory potential vs. in vitro
      targets, such as enzyme activity of matrix metalloproteinases and cytokine
      generation. MATERIAL: 124 male Wistar Lewis rats; for the in vitro studies human
      matrix metalloproteinases and human mononuclear cells were used. TREATMENT:
      Arthritis was induced by injection of complete Freund adjuvant. Drugs (2, 15, 50
      mg tiaprofenic acid/kg; 5, 15, 30 mg doxycycline/kg) were administered daily p.o.
      until day 21. In the in vitro studies 10-1000 mumoles/l of these drugs were used.
      METHODS: Urinary levels of pyridinoline and deoxypyridinoline, determined by
      HPLC/fluorescence, and paw volumes were the measurements in the rat study. In the
      in vitro studies enzyme activities were assessed using fluorogenic peptide
      substrates; cytokines were determined by ELISA. RESULTS: On day 21 of disease
      crosslink excretion was about twofold higher compared to the healthy controls.
      After administering daily 15 or 30 mg/kg tiaprofenic acid p.o. this increase was
      almost completely prevented whereas the paw volumes were suppressed by about 50%.
      Up to 50 mg/kg doxycycline did not display significant suppressive effects on
      crosslinks and paw volumes. In vitro 50-100 mumol/l of both drugs inhibited the
      activities of selected metallo-proteinases, but only doxycycline suppressed the
      generation of IL-1 beta/TNF alpha in human mononuclear cells, whereas tiaprofenic
      acid was virtually inactive in that model. CONCLUSIONS: In arthritic rats
      tiaprofenic acid has not only the capability to suppress paw inflammation, but
      also to prevent with high potency the excretion of pyridinium crosslinks.
      Doxycycline without inherent antiinflammatory activity does not exhibit such
      preserving effects on collagen degradation in this model. Thus the mode of action
      of cartilage protecting drugs within the complex pathogenesis of arthritis will
      need further elucidation.

PMID- 9266273
TI  - Acute myocardial infarction enhances the portal venous histamine level in dogs.
AB  - OBJECTIVE AND DESIGN: The aim of our experiments was to determine the plasma
      histamine level in the portal venous (VP) blood during acute coronary occlusion
      and reperfusion. SUBJECTS: 27 adult mongrel dogs of either sex were randomized
      for three groups: sham-operated controls, occlusion group (group O) and
      reperfusion group (group R). TREATMENT: The left circumflex coronary artery (LCx)
      was proximally occluded and the occlusion was maintained during 6 h (group O), or
      after a 60-min occlusion the LCx was reperfused (group R). The portal vein was
      cannulated to take blood samples for hormone measurements. METHODS: The plasma
      histamine concentrations were measured with the radioenzymatic method. RESULTS:
      The VP plasma histamine level was significantly increased 60 min after the LCx
      occlusion in groups O (99.9 +/- 40.2 vs. 252.9 +/- 100 pg/ml, mean +/- SD) and R
      (101.2 +/- 55.1 vs. 179.8 +/- 96 pg/ml), and remained high in group O (240.4 +/-
      81 pg/ml), while 2 h after LCx reperfusion it had decreased to the basic level.
      There was no correlation between the hemodynamic parameters and the portal vein
      plasma histamine levels. CONCLUSIONS: Histamine is released into the
      gastrointestinal tract during acute myocardial ischemia and reperfusion, but the
      release of the vasoactive drug has no effect on systemic hemodynamics.

PMID- 9266274
TI  - Sex, gonads, sex hormones and histamine-stimulated gastric acid and serum
      pepsinogen.
AB  - OBJECTIVE AND DESIGN: The effects of sex, sex hormones and gonads were studied in
      dogs because men secrete more acid than woman and duodenal ulcer is commoner in
      men and remits in pregnancy and after stilboestrol. MATERIAL: Four male and 4
      female greyhounds with chronic gastric fistulas were tested. METHODS: Histamine
      was infused i.v. 1-16 micrograms/min and plateau acid output measured in the last
      30 min of each 60 min infusion. TREATMENT: The gonads were then removed and
      secretion retested. The orchidectomised dogs were then given stilboestrol 2 mg
      daily (+/-progesterone 25 mg i.m. three times a week) and the oophorectomised
      bitches given testosterone propionate 25 mg twice weekly i.m. and secretion again
      retested. RESULTS: Submaximal and maximal acid outputs (and serum pepsinogen) of
      dogs and bitches were similar and correlated with body weight. Gonadectomy did
      not alter these functions nor did hormones of the opposite sex given for 1-12
      months. CONCLUSIONS: In the dog, as in the rat, and probably in man, histamine
      stimulated gastric acid output is a function of body size and not of sex.

PMID- 9266275
TI  - SH3 domain-mediated interactions involving the phox components of the NADPH
      oxidase.
AB  - OBJECTIVE AND DESIGN: To derive a model describing the SH3 domain-mediated
      assembly of the activated NADPH oxidase. MATERIALS: Recombinant SH3 domain and
      Pro-rich fusion proteins were used to investigate potential co-associations.
      METHODS: Interactions were assessed using biotinylated overlay assays and the
      yeast two hybrid system. Association with p47phox from cell lysates was examined
      by immunoblot analysis. RESULTS: The association between p47- and p22phox
      involves the SH3 domains of p47phox functioning in tandem. The Prorich motif in
      p47phox interacts with both p40phox and the COOH-terminal SH3 domain of p67phox.
      CONCLUSIONS: In the resting cell, the Pro-rich motif of p47phox interacts with
      the SH3 domain of p40phox, which in turn associates with p67phox. Upon
      activation, the p47-p40phox regulatory complex dissociates, permitting the
      association of p47phox with the COOH-terminal SH3 domain of p67phox. This complex
      translocates to the plasma membrane and associates with cytochrome b558, via
      interaction of the tandem SH3 domains of p47phox with the p22phox Pro-rich motif.

PMID- 9266277
TI  - Tumor antigens recognized by T lymphocytes.
AB  - In the last five years, knowledge of human tumor antigens recognized by
      autologous cytolytic T lymphocytes (CTL) has increased considerably. So far,
      genetic and biochemical approaches have led to the molecular identification of
      three classes of antigens. Most of these antigens consist of peptides that are
      presented to T cells by HLA molecules. The first class comprises antigens encoded
      by genes such as MAGE, BAGE, and GAGE, which are expressed in various tumors of
      different histological origins, but not in normal tissues other than testis. The
      second class represents differentiation antigens encoded by genes that are only
      expressed in melanoma and normal melanocytes like tyrosinase, Melan-A/MART-1,
      gp100 and gp75. The third class includes antigens produced by unique point
      mutations in genes that are ubiquitously expressed. In most cases, the antigenic
      peptide is encoded by the mutated region of the gene. A number of these antigens
      provide promising targets for new protocols of specific cancer immunotherapy.

PMID- 9266276
TI  - Ex vivo inhibition of beta-thromboglobulin release following administration to
      man of ABT-299, a novel prodrug of a potent platelet activating factor
      antagonist.
AB  - OBJECTIVE AND DESIGN: ABT-299 is a prodrug that is converted by serum esterase to
      a potent platelet activating factor (PAF) antagonist (A-85783). In order to
      evaluate the pharmacological activity of this antagonist in man the effect of ABT
      299 given to healthy volunteers on ex vivo PAF-induced beta-thromboglobulin (beta
      TG) release in blood was assessed. SUBJECTS: 37 healthy male volunteers, age 18
      to 40 (mean age of 23.6 years) and free of medication, participated in the study.
      TREATMENT: Subjects were administered intravenously 0.8 mg, 2 mg, or 70 mg doses
      of ABT-299 (6-7 subjects per group) or placebo (9 subjects, pooled). METHODS:
      Peripheral blood taken over 12 h after dosing was used for ex vivo beta-TG
      release and, in the case of the 70 mg dose, measurement of plasma drug
      concentration. Data were compared by Student's t-test. RESULTS: All three doses
      produced highly significant inhibition (p < 0.005 compared to predose values) of
      PAF-induced beta-TG release (units/ml plasma +/- SEM) 12 h after drug
      administration (54 +/- 14 vs. 405 +/- 51, n = 8; 79 +/- 23 vs. 480 +/- 127, n =
      7; 21 +/- 10 vs. 327 +/- 72, n = 6, respectively) whereas there was no
      significant difference in beta-TG release in the placebo group (449 +/- 90 vs.
      307 +/- 49, n = 9). Inhibition was associated with the rapid appearance in plasma
      of A-85783 and the pyridine N-oxide metabolite of A-85783. Within 2 h, the plasma
      concentration of the metabolite exceeded that of the parent drug. Both the parent
      drug and the metabolite exhibited potent in vitro inhibition of PAF-induced beta
      TG release (A2 values of 4 and 1 nM respectively). CONCLUSIONS: These studies are
      the first to illustrate the utility of the beta-TG release assay for assessing ex
      vivo activity of PAF antagonists. These studies also demonstrate that the
      administration of ABT-299 to man results in potent, long lasting inhibition of
      PAF-mediated platelet activation, due in part to the pyridine-N-oxide metabolite,
      and support the potential therapeutic utility of this prodrug in treating PAF
      mediated diseases.

PMID- 9266278
TI  - Inhibitory receptors for HLA class I molecules on cytolytic T lymphocytes.
      Functional relevance and implications for anti-tumor immune responses.
AB  - In recent years, the molecular mechanism by which natural killer cells lyze, or
      fail to lyze, different target cells has been elucidated. Natural killer cells
      express receptors which recognize MHC class I molecules on target cells. This
      interaction leads to inhibition of cytolytic activity, thus preventing lysis of
      target cells. The receptors belong to two distinct molecular types: (1) the lg
      superfamily which includes receptors (p58.1, p58.2, p70, and p140) which
      recognize specific HLA allotypes; (2) CD94 molecules which display a broad
      specificity for HLA class I molecules. Recently, a subset of cytolytic T
      lymphocytes has been shown to express the various natural killer cell receptors.
      Such T cells are detectable in peripheral blood, spleen, tonsils, and lymph
      nodes, but not in the thymus and cord blood. In some instances, two or more
      natural killer receptors can be coexpressed at the single cell level. Surface
      marker analysis has revealed that natural killer cell receptor-positive T cells
      always express a memory phenotype. Moreover, they are characterized by a skewed T
      cell receptor V beta repertoire. Further analysis of the T cell receptor VDI
      sequences revealed that natural killer cell receptor-positive, CD3-positive cells
      isolated from a given individual are oligoclonal or monoclonal in nature.
      Crosslinking of natural killer receptors leads to inhibition of different T cell
      functions, including non-specific lysis of appropriate HLA class I-negative
      target cells, T cell receptor mediated cytotoxicity, and cytokine production. The
      inhibitory effect on T cell receptor-mediated function has important
      implications. Thus, the expression of natural killer cell receptors as a
      consequence of chronic antigen stimulation may result in functional impairment of
      specific cytolytic T lymphocytes. Preliminary data indicate that this phenomenon
      may occur in tumor or virally infected patients. Remarkably, various patients
      with large granular lymphocyte expansions characterized by a CD3/ natural killer
      receptor-positive phenotype had chronic viral infections. The fact that antigen
      specific cytolytic T lymphocytes may simultaneously express T cell and natural
      killer cell receptors, both recognizing HLA class I molecules but mediating
      opposite signals, offers new perspectives in our appreciation of the regulation
      of T cell responses and offers new clues for understanding the immunopathological
      events involved in certain diseases.

PMID- 9266279
TI  - Altered MHC class I antigens in tumors.
AB  - MHC class I antigens are lost or downregulated in invasive tumors compared with
      autologous normal tissues. This is observed in most of the newly induced
      experimental tumors analyzed if they are cloned before passaging in vivo.
      Similarly, this is observed in 40%-90% of human tumors using the available panel
      of anti-HLA class I monoclonal antibodies. In both systems the tumor populations
      are heterogeneous for H-2/HLA expression and composed of clones that express
      different amounts of MHC class I antigens. This heterogeneity may have a profound
      influence on tumor behavior, considering the role that MHC antigens play in T and
      natural killer cell-mediated responses. It is possible that the tumor escape
      mechanisms from T and natural killer cells select variants that express a
      particular MHC class I altered phenotype. We review the MHC changes detected in
      different experimental as well as human tumors and demonstrate the relevance of
      these altered H-2/HLA tumor phenotypes for implementing immunotherapeutic
      strategies based on T or natural killer cell-mediated responses.

PMID- 9266280
TI  - T-cell recognition of melanoma antigens and its therapeutic applications.
AB  - During the last few years, tumor immunology has gained impetus due to the
      molecular definition of T-cell-recognized antigens and the mechanisms of such
      recognition, antigen processing, and presentation. To date, the majority of the
      identified melanoma antigens are shared among different melanomas and some are
      also expressed in tumors of different histology. However, unique antigens
      expressed solely by the melanoma autologous to the T-cell used for their
      characterization were also found. The identification of the immunogenic peptides,
      the minimal target entity required for T-cell recognition, has provided novel
      reagents for the development of peptide-based immunotherapy. These findings,
      together with the understanding of requirements for T-lymphocyte recognition and
      activation, allow the design of new therapeutic protocols. In addition, the large
      body of data now available on the fine mechanism of antigen processing and
      presentation have revealed not only the role of the MHC molecules but also that
      of other intracellular proteins, such as transporter associated with antigen
      processing-1 and -2 and proteosome-related molecules. These findings suggest
      that, in order to select patients eligible for vaccination, the expression of the
      MHC allele involved in T-cell recognition, the profile of tumor antigens, and the
      status of the antigen-processing system should be carefully evaluated in tumors
      cells of prospective patients. In this review, some of the basic concepts of
      immune recognition and the current view of melanoma tumor antigens recognized by
      T-lymphocytes will be discussed along with the potential application of these
      findings in designing new therapeutic strategies.

PMID- 9266281
TI  - HIV-1-infected monocytes and monocyte-derived macrophages are impaired in their
      ability to produce superoxide radicals.
AB  - Monocytes and monocyte-derived macrophages play a key role in immune defense
      against pathogenic organisms. Superoxide anion production is a key mechanism by
      which phagocytes kill pathogens. We sought to determine whether human
      immunodeficiency virus-infected monocytes and monocyte-derived macrophages are
      compromised in their ability to produce the superoxide anion following
      stimulation with phorbol myristate acetate (PMA) or after cross-linking the type
      I Fc receptor for IgG (Fc gamma RI). Fc gamma RI was cross-linked by the binding
      of monoclonal antibody 197, which reacts with an epitope of Fc gamma RI via its
      Fc region. Monocytes and monocyte-derived macrophages obtained from seronegative
      donors were infected in vitro with human immunodeficiency virus-1JR-FL and used
      in effector assays that measured superoxide anion production by the reduction of
      nitroblue tetrazolium. Reduced nitroblue tetrazolium was measured
      spectrophotometrically and by microscopy in which the percentage of cells
      containing intracellular deposits of the dye was assessed. By spectrophotometric
      measurement, we found that human immunodeficiency virus-infected monocytes and
      monocyte-derived macrophages produced less superoxide anion following either
      phorbol myristate acetate stimulation or Fc gamma RI cross-linking than
      uninfected cells from the same donor. Using microscopy we saw no difference in
      the percentage of infected and uninfected macrophages containing intracellular
      deposits of nitroblue tetrazolium suggesting that human immunodeficiency virus
      infected macrophages produce less superoxide anion on a per cell basis than
      uninfected macrophages. Activation of human immunodeficiency virus-infected
      monocytes with interferon-gamma for 72 h prior to stimulation with phorbol
      myristate acetate or monoclonal antibody 197 increased their ability to reduce
      nitroblue tetrazolium. These findings suggest that impairment in the production
      of reactive oxygen intermediates may, in some cases, contribute to the
      pathogenesis of human immunodeficiency virus infection and the acquired
      immunodeficiency syndrome.

PMID- 9266282
TI  - Benzydamine inhibits the release of tumor necrosis factor-alpha and monocyte
      chemotactic protein-1 by Candida albicans-stimulated human peripheral blood
      cells.
AB  - Benzydamine is a non-steroidal antiinflammatory drug, devoid of activity on
      arachidonic acid metabolism, which is extensively used as a topical drug in
      inflammatory conditions, particularly for the treatment of bacterial vaginosis
      and Candida albicans-sustained vaginitis. In the present study the effects of
      benzydamine on the production of several inflammatory cytokines were examined in
      cultures of Candida albicans-stimulated human mononuclear cells. Benzydamine
      (6.25-50 microM) inhibited Candida-induced tumor necrosis factor-alpha and, to a
      lesser extent, interleukin-1 beta production, whereas it did not affect
      interleukin-6 release. Benzydamine also blocked monocyte chemotactic protein-1
      secretion, but it did not affect interleukin-8 production. Unlike benzydamine,
      ibuprofen and naproxen, two non-steroidal antiinflammatory drugs also used
      topically, were unable to suppress inflammatory lymphokine production from
      Candida-activated mononuclear cells. These data suggest that benzydamine may be
      effective in local Candida infections at least in part by suppressing
      inflammatory cytokine and monokine production in the vaginal mucosa and
      consequently decreasing their levels in vaginal secretions.

PMID- 9266283
TI  - Lactate blood levels in the perioperative period of orthotopic liver
      transplantation.
AB  - To investigate whether early postoperative changes in blood lactate concentration
      indicate the functional recovery of the newly grafted liver, changes in oxygen
      supply, oxygen consumption, acid-base equilibrium, and blood lactate
      concentrations were prospectively studied in a group of 53 postnecrotic cirrhotic
      patients during the various phases of orthotopic liver transplantation
      (preanhepatic, anhepatic, neohepatic) and for the first 48 h following
      reperfusion. The patients were divided into two groups according to the quality
      of the early graft function, as indicated by alanine aminotransferase, bile flow,
      and prothrombin activity: group A (49 patients), good immediate graft function
      and group B (4 patients), immediate graft non-function. Lactate levels rose in
      the same manner during the preanhepatic and anhepatic stages and peaked after
      revascularization of the graft. Following reperfusion, however, distinctly
      different blood lactate profiles were recorded in the two groups of patients. A
      fall in lactate concentration was recorded in group A patients, whereas a
      continuous rise occurred in group B patients: the difference becoming significant
      by the end of surgery (P < or = 0.05). During the first 48 h following
      revascularization of the graft, opposite trends in lactate concentration, bile
      flow, alanine aminotransferase, and prothrombin activity were evident in the two
      groups of patients: 24 h after reperfusion, lactate levels were below 2 mmol/l in
      47 of 49 patients from group A, while they plateaued above 4 mmol/l in all
      patients from group B. Group A patients had lower alanine aminotransferase levels
      (P < or = 0.001), higher prothrombin activity, (P < or = 0.01), and greater bile
      flow (P < or = 0.02). If validated in larger series, the blood lactate profile,
      probably more than the absolute level, appears to be a useful indicator of the
      early recovery of liver metabolic capacities in the immediate postoperative
      period of orthotopic liver transplantation.

PMID- 9266284
TI  - Effects of substance P on human T cell function and the modulatory role of
      peptidase inhibitors.
AB  - Evidence has been presented for a modulatory role of surface peptidases on
      substance P-mediated immune responses. In this study, we first characterized the
      effects of substance P and its carboxy- and amino-terminal fragments on human
      lymphocyte proliferative responses to investigate whether peptidase inhibitors
      influence the effects of the neuropeptide. Substance P at 10(-7) M and the
      carboxy-terminal fragment SP(4-11) slightly enhanced the lymphocyte responses to
      phytohemagglutinin and concanavalin A. In contrast, the amino-terminal fragment
      SP(1-4) failed to have any positive effect. However, in the presence of
      dipeptidylpeptidase IV/CD26 and neutral endopeptidase/CD10 inhibitors (diprotin A
      and thiorphan, respectively), the effect of substance P on mitogen-induced
      proliferation was significantly increased. These data support the hypothesis that
      lymphocyte surface peptidases play a modulatory role in the effects of substance
      P on T cell function.

PMID- 9266285
TI  - Plasma levels of tumor necrosis factor-alpha and interferon-gamma in Sicilian
      children with Mediterranean spotted fever.
AB  - The plasma levels of tumor necrosis factor-alpha and interferon-gamma were
      measured in 53 consecutive children with serologically confirmed Mediterranean
      spotted fever and were found to be increased during the acute phase compared with
      the convalescent phase (tumor necrosis factor-alpha mean 32.17 vs. 4.12 pg/ml, P
      < 0.0001; interferon-gamma mean 84.17 vs. 2.65 pg/ml, P = 0.0006). Plasma levels
      of both cytokines were higher in patients with a typical exanthema rather than
      those with a very mild or no exanthema; tumor necrosis factor-alpha levels were
      significantly lower in the latter (tumor necrosis factor-alpha 32.17 vs. 9.85
      pg/ml, P < 0.0001; interferon-gamma 84.17 vs. 38.14 pg/ml, P = 0.35). Tumor
      necrosis factor-alpha and interferon-gamma may be harmful or beneficial to the
      infected host, depending upon the amounts produced and whether they are
      circulating or confined locally to the site of inflammation.

PMID- 9266286
TI  - Pharmacokinetic-pharmacodynamic relationships for analgesics.
AB  - A major goal of current pain research is to develop scientifically-based
      guidelines to optimize selection of analgesic drug doses and control pain.
      Numerous clinical studies have shown that the drug dose required to effectively
      alleviate pain is often highly variable, both between patients and between pain
      episodes in individual patients. This high variability makes it difficult to
      predict appropriate dosing regimens that will adequately control pain in the
      individual patient. The result is a "trial and error" approach to analgesic
      therapy. Experimental tools that measure analgesic response and drug disposition
      after administration of analgesics can be used to better predict the therapeutic
      effects of analgesics in individual patients. The approach defines factors that
      contribute to variability in therapeutic response. Pharmacokinetic
      pharmacodynamic (PK/PD) modeling involves analysis of drug disposition data and
      drug efficacy data. Modeling depends on sensitive and reliable methods to
      quantify both pain and plasma (or other body fluid) levels of analgesic agents.
      Two major approaches have been used to quantify pain. The first utilizes
      subjective reports from patients, while the second employs physiological
      correlates of pain, such as evoked potentials. Results from PK/PD analysis that
      successfully identify a relationship between drug dose, drug concentration, and
      effect can be used to predict the effects of drug dose on analgesic effect in
      individuals. The ultimate goal is to provide patients with better pain relief by
      understanding variables that affect the analgesic concentration/effect
      relationship. This review examines the available pharmacokinetic-pharmacodynamic
      (PK/PD) data for selected opioid and nonopioid analgesics. Even though most
      analgesics are used clinically in multiple doses, the majority of PK/PD studies
      conducted to date evaluate single dose effects. Further studies with multiple
      doses are required to evaluate the validity of PK/PD relationships defined from
      single dose studies.

PMID- 9266288
TI  - Comparative bioavailability of two capsule formulations of mefenamic acid.
AB  - Pharmacokinetic behavior of single dose of 2 mefenamic acid capsule formulations
      was studied in a randomized crossover design in 22 healthy male volunteers.
      Following ingestion of 250 mg of either of the products, blood samples were
      obtained over a 14-hour period and the serum drug concentrations were determined
      by an HPLC assay with ultraviolet detection at 280 nm. The parametric 90%
      confidence intervals of the mean value of the ratio (fendol (test)/ponstan
      (reference)) of pharmacokinetic parameters were 0.88-1.07, 0.94-1.19, and 0.89
      1.16 for AUC zero-infinity, Cmax and T1/2. In each case values were within the
      acceptable bioequivalence range of 0.8-1.25. Distribution-free point estimate for
      the difference in expected medians of Tmax of the 2 formulations (fendol-ponstan)
      was -0.5 hours with a 90% confidence interval of -1.0 to -0.25 which overlaps
      with the stipulated bioequivalence range of +/-0.48. The kinetic parameters a
      comparable to what is reported for mefenamic acid and there were no statistically
      significant differences in any of them when comparing the 2 products by ANOVA on
      log-transformed data. Although the 2 products are not equivalent regarding the
      secondary parameter Tmax, still the data indicate that they could be considered
      bioequivalent regarding rate of absorption (Cmax), extent of absorption (Cmax and
      AUC), and elimination (t1/2).

PMID- 9266287
TI  - Comparative bioavailability of two atenolol tablet formulations in healthy male
      volunteers after a single dose administration.
AB  - The bioavailability of 2 atenolol tablet formulations (Angipress from
      Laboratorios Biosintetica, and Atenol from Wellcome ICI Laboratory, Brazil) were
      compared in 18 healthy male volunteers who received a single 50 mg dose of each
      atenolol formulation. The study was conducted following an open randomized 2
      period crossover design with a 14-day washout interval between doses. Plasma
      samples were obtained over a 24-hour interval and atenolol concentrations were
      determined by HPLC with fluorimetric detection. From the plasma atenolol
      concentration vs time curves the following pharmacokinetic parameters were
      obtained: AUC(zero-24) (area under the concentration vs time curves from 0-24 h),
      ke (terminal elimination constant), t1/2 (terminal first order elimination half
      life), AUC (area under the concentration vs time curves extrapolated to
      infinity), Cmax (maximum achieved concentration), Tmax (time to achieve Cmax) and
      Cmax/AUC. All these variables were analyzed using both parametric and
      nonparametric statistics. Geometric mean Angipress/Atenol individual percent
      ratios were 99.6% for AUC(zero-24), 99.7% for AUC, 98.0% for Cmax, 102.8% for
      t1/2, 97.2% for ke and 97.8% for Cmax/AUC, with all their 90% confidence
      intervals within the bioequivalence range 80-125%, thus showing similar patterns
      of absorption and disposition. Arithmetic mean for individual Tmax differences
      was 0.8 h, and the 90% confidence interval did not include the zero value. Based
      on these results and in accordance with the European Union and the US Food and
      Drug Administration bioequivalence requirements we conclude that both atenolol
      formulations are bioequivalent for both the extent and the rate of absorption.

PMID- 9266289
TI  - Analysis of metabolites--a new approach to bioequivalence studies of
      spironolactone formulations.
AB  - The aldosterone antagonist spironolactone undergoes extensive and complex
      biotransformation. For investigation of bioequivalence of 2 oral spironolactone
      formulations, Spironolacton 50 Heumann and Aldactone 50, the pharmacokinetics and
      bioequivalence of the parent drug and 2 predominant active metabolites, canrenone
      and 7 alpha-thiomethylspirolactone, were determined in a 2-way crossover study in
      24 young healthy male volunteers after multiple oral dosing of 100 mg once daily.
      Plasma samples were measured by a newly developed HPLC assay and individual
      pharmacokinetic parameters of the 3 compounds were calculated by use of
      noncompartmental techniques. Statistical analysis was performed by ANOVA and
      nonparametric methods. Spironolactone was rapidly cleared from plasma. Therefore,
      only Css,max and tss,max were determined. Concerning Css,max bioequivalence was
      found with 90% classical shortest confidence interval ranging from 80.7-112.4%.
      The intrasubject variability for Css,max was determined to be 28.1%. Higher and
      persisting concentrations were observed for the metabolites. For canrenone 90%
      classical shortest confidence intervals were calculated as 95.4-105.0% for
      AUCss,tau, as 92.9-105.8% for Css,max, and as 89.1-106.3% for peak trough
      fluctuation (PTF). In the case of 7 alpha-thiomethylspirolactone the values were
      84.2-103.0% for AUCss,tau, 77.0-98.6% for Css,max, and 85.0-100.4% for PTF. For
      tss,max nonparametric 90% confidence intervals were determined as 0.00 to 1.50 h
      for spironolactone and canrenone and as -0.50 to 1.00 h for 7 alpha
      thiomethylspirolactone. The intraindividual variability was below 30% for all
      pharmacokinetic parameters in the case of the metabolites. Thus, bioequivalence
      of the test and the reference formulation can be concluded. The study suggests
      the inclusion of parent compound and metabolites for bioequivalence testing of
      spironolactone formulations. Intraindividual subject variability was clearly
      diminished by investigating bioequivalence under steady-state conditions.

PMID- 9266290
TI  - Pharmacokinetics of the controlled-release nisoldipine coat-core tablet
      formulation.
AB  - The pharmacokinetics, safety, and tolerability of the novel once-daily "coat
      core" formulation of the calcium antagonist nisoldipine were investigated in 4
      randomized nonblind studies A-D in 52 healthy volunteers. Immediate-release or
      intravenous formulations were administered as reference in 3 studies. The
      objective of the present studies was to select the optimum controlled-release
      formulation (A), compare it to the immediate-release tablet at steady-state (B),
      determine the absolute bioavailability (C), and investigate bioequivalence after
      a small change in composition (D). Comparative pharmacokinetic properties: Mean
      residence time and apparent terminal half-life of nisoldipine in the coat-core
      formulation were significantly increased in comparison to administration via the
      intravenous route or the oral immediate-release formulation. Concentration
      profiles could be described with a 3-segment input model. Steady-state conditions
      were established with the second dose of nisoldipine coat-core and accumulation
      from first dose to steady-state accounted for 46% as expected due to the
      contribution of AUC beyond 24 h. At steady-state the coat-core formulation
      produced a plateau-shaped profile of nisoldipine plasma concentrations throughout
      the 24 h dosing interval and the peak-trough fluctuation was reduced by
      approximately 4-fold, compared to the immediate-release tablet in a b.i.d.
      regimen. While the absolute bioavailability of the drug in the coat-core tablet
      was 5.5%, its relative bioavailability was greater by 1.5-fold compared to the
      immediate-release tablet. This can be attributed to release of drug in the colon
      where the contribution of the gut wall to presystemic metabolism is reduced
      resulting in an increase in bioavailability as compared to stomach and small
      intestine. The intersubject variability of nisoldipine coat-core pharmacokinetics
      was comparable to that of the immediate-release tablet. The within-subject
      (intraindividual) variability was considerably smaller. Based on its
      pharmacokinetic profile the side chain-hydroxylated metabolite M 9 is not
      expected to contribute significantly to the antihypertensive effect of
      nisoldipine coat-core. In vitro/in vivo correlation: There was a rank order
      correlation between in vitro release rate of 3 different nisoldipine coat-core
      formulations and their noncompartmental pharmacokinetic parameters, a decrease in
      dissolution rate leading to increased bioavailability in vivo. Likewise, the mean
      dissolution times in vitro and in vivo were correlated in rank order. A linear
      (level A) correlation could be established within approximately 0-6 hours (in
      vitro) corresponding to 0-12 hours in vivo. The change in slope of the
      correlation curve after approximately 12 hours (in vivo) most likely reflects
      changes in both rate and extent of nisoldipine absorption in different sections
      of the gastrointestinal tract. SAFETY: In the present studies the drug was safe
      and well tolerated, adverse events related to peripheral vasodilatation being
      less frequent with the coat-core tablet compared to intravenous or immediate
      release formulations.

PMID- 9266291
TI  - Resection of the proximal row of the carpus. A review of 45 cases.
AB  - The authors present a review of 45 proximal carpectomies performed for various
      reasons between 1986 and 1995. The pre- and postoperative assessment was clinical
      and radiological, and the intra-operative analysis was based on the status of the
      cartilage of the radiolunate joint, and of the head of the capitate.
      Postoperative assessment was based on the biomechanical behaviour of the wrist
      after surgery. At the final follow-up, the authors noted that pain was improved
      in 90% and functional movement was preserved in 70% of patients. There was
      approximately 20% loss of strength when compared to the opposite hand.

PMID- 9266292
TI  - Clinical manifestations of Kashin-Beck disease in Nyemo Valley, Tibet.
AB  - Clinical manifestations of Kashin-Beck disease have been studied in Central
      Tibet. Statistical analysis of physical signs allowed a definition of the
      clinical diagnosis and a scale for the functional severity for the disease to be
      drawn up. This classification is used for the assessment of patients who received
      palliative physical treatment. A group of 136 patients have been examined and
      their disabled joints classified according to pain, bony enlargement and
      restriction of movement. 57% were between 20 and 35 years of age. The patients
      mainly complained about their distal weightbearing joints. The clinical evolution
      of the disease is described from childhood to adult life.

PMID- 9266293
TI  - Arthrolysis of the shoulder for ruptures of the rotator cuff.
AB  - Complete repair of tears of the rotator cuff may be difficult, but with superior
      arthrolysis by the Apoil-Dautry technique the lesion in the cuff is not treated.
      We report 17 patients who had this procedure for large cuff defects. The outcome
      is directly related to the duration of symptoms, and we only had good results in
      a few patients, although intensive physiotherapy improves function. A wide
      debridement is needed, followed by intensive physiotherapy for the deltoid and
      shoulder stabilising muscles. We recommended that this technique should be used
      in elderly patients who will put less demand on their shoulders.

PMID- 9266294
TI  - Anterior cruciate ligament reconstruction by mini-arthrotomy.
AB  - We present 50 consecutive patients with chronic anterior cruciate deficiency
      treated by reconstruction of the ligament through a limited arthrotomy using the
      middle third of the patellar tendon as a graft. The patients were all men with a
      mean age of 26 years (range 17 to 36 years) with an average follow up of 24
      months. There were good or excellent results as measured by the Lysholm score in
      41, and in 27 with the ARPEGE score. Movements were full in 46 and retropatellar
      pain was experienced by 4.

PMID- 9266295
TI  - No indications for percutaneous lumbar discectomy?
AB  - A questionnaire was used to assess the outcome of automated percutaneous lumbar
      discectomy (APLD), to correlate patients' data and to identify criteria for pain
      relief and patient satisfaction. Two hundred and thirty eight patients were
      operated on by APLD between 1988 and 1990. The questionnaire returned by 182
      patients (76.4%) was suitable for evaluation. The mean follow-up was 2.5 years.
      Overall, 60% reported pain relief and 52% were satisfied with APLD. Conventional
      operations were carried out subsequently on 45 patients (25%). Bivariate and
      multivariate analyses were done for preoperative (age, gender, neurological
      deficit, Lasegue's sign, sports activity), perioperative (weight of disc material
      removed, level of APLD) and post-operative (conventional nucleotomy, change in
      condition, pain relief, satisfaction, sports activity, return to work,
      compensation claims) parameters. The only significant parameters for improvement
      in condition and pain relief was age, where patients younger than 41 do better.
      Risk factors for reoperation were a positive Lasegue's sign and over 41 years of
      age. Patient satisfaction was significantly higher for patients without sensory
      deficit preoperatively.

PMID- 9266296
TI  - Lateral disc herniation following percutaneous lumbar discectomy. A case report.
AB  - A case of lateral disc herniation in the lumbar spine which occurred soon after
      percutaneous discectomy is described. This is a rare complication, but in this
      patient it appeared that the extrusion occurred through the hole in the annulus
      made at the first operation.

PMID- 9266297
TI  - The action of prostaglandin E2 and triamcinolone acetonide on the firing activity
      of lumbar nerve roots.
AB  - Sciatica, due to lumbar disc herniation, is understood electrophysiogically to be
      an ectopic firing originating from a nerve root. The recent concept of chemical
      radiculitis implies the involvement, not only of mechanical compression, but also
      of chemical mediators which contribute to the generation of ectopic firing. The
      present study demonstrates that prostaglandin E2, a chemical mediator of
      inflammation, provoked the ectopic firing of nerve roots in a canine in vitro
      model which indicates that it may play a part in the irritation of nerve roots.
      In contrast, triamcinolone acetonide suppressed the firing induced by
      prostaglandin suggesting that steroids may be effective in the treatment of root
      symptoms.

PMID- 9266298
TI  - Retrograde ejaculation after retroperitoneal lower lumbar interbody fusion.
AB  - We have studied the incidence and functional outcome of retrograde ejaculation as
      a postoperative complication of anterior lumbar interbody fusion. A
      questionnaire, specifically designed to analyse this problem, has been used over
      a 6 to 13 year follow-up. Out of 50 men, 41 completed the questionnaire; 2
      complained they had permanent retrograde ejaculation after the operation; one
      stopped ejaculating for 6 months, and thereafter had a 50% reduction. The Dallas
      pain questionnaire showed that retrograde ejaculation did not have a negative
      effect on the functional outcome, but male genital dysfunction was a complication
      of anterior spinal fusion in 8% of cases.

PMID- 9266299
TI  - Posterior approach for radical excision of sacral chordoma.
AB  - Sacral chordoma is a rare primary malignant tumour of bone. Operations to excise
      these tumours are complex, time consuming and involve considerable blood loss. We
      describe the use of a posterior approach to excise chordomas from the sacrum of
      five patients without visceral involvement. This approach is less complex than
      combined approaches previously described. No distal recurrences had occurred at a
      mean followup of 5 years. One patient developed local recurrence and was
      successfully treated by wide local excision. Postoperative morbidity was low with
      regard to urinary and faecal continence problems. We recommend the use of
      Mersilene mesh to prevent herniation through the sacral defect.

PMID- 9266300
TI  - Expansive laminoplasty for lumbar intradural lipoma.
AB  - We evaluated the pre- and postoperative neurological state of 3 patients with
      lumbar intradural lipoma. Total resection of the lipoma in the cauda equina was
      impossible, and partial resection and expansive laminoplasty was carried out.
      Subsequent neural involvement may depend on the duration of symptoms rather than
      the extent of resection. Expansive laminoplasty is appropriate in these
      circumstances since decompression is combined with spinal stabilization.

PMID- 9266301
TI  - Measurement of total and local bone morphogenetic protein concentration in bone
      tumours.
AB  - Bone morphogenetic protein (BMP) has been shown to be one of the significant
      factors in the prognosis of bone tumours. In normal development BMP induces new
      bone formation and later takes part in fracture healing, but its function in
      malignant tumours is not known. In this study the concentration of bone
      morphogenetic protein was measured in primary bone tumours by two methods. Local
      staining intensity was detected immunohistologically by the avidin-biotin
      peroxidase method determining the highest dilution of anti-serum against bovine
      bone morphogenetic protein. The total amount of BMP in a tumour sample was
      measured by an enzyme-linked immunosorbent assay technique after digesting the
      tissue with collagenase to remove proteins from the connective tissue.
      Immunohistochemical staining showed that bone morphogenetic protein was present
      in the cytoplasm and in reactive bone formed by malignant cells. The local
      concentration was highest in the tissue of giant cell tumours compared to
      chondrosarcoma, osteosarcoma and benign bone tumours. The total amount in
      malignant bone tumours was 2.4 times higher compared to benign bone tumours.

PMID- 9266302
TI  - The use of a coral composite implant containing bone morphogenetic protein to
      repair a segmental tibial defect in sheep.
AB  - A composite implant consisting of a coral cylinder, moose bone morphogenetic
      protein and type IV collagen was used to repair a segmental tibial defect in
      sheep. Healing, related variance in mechanical strength and immune responses were
      evaluated. In comparison with a coral control, a larger amount of newly formed
      external callus was observed in the composite group at 6 weeks. The maximal
      torque capacity, maximal angular deformation at failure and bone stiffness of a
      healed osteotomised tibia recovered 113%, 117% and 120% in the coral controls and
      67%, 92% and 79% in the composite implants against the corresponding
      contralateral tibia at 16 weeks respectively. A significantly elevated anti-BMP
      antibody was detectable in the composite group at 3 and 6 weeks. Augmented bone
      formation at an early stage and weakened torsional performance at a later stage
      in the composite implants may indicate the phase-specific osteoinduction and the
      immune response of xenogenic BMP with time.

PMID- 9266303
TI  - Displaced subcapital fracture of the hip in transient osteoporosis of pregnancy.
      A case report.
AB  - We describe a case of displaced subcapital fracture of the hip in a woman in the
      third trimester of her first pregnancy. A pathological fracture occurred in a
      previously painful hip, and radiographs showed pronounced osteopenia of the
      femoral head and neck. Closed reduction and internal fixation was carried out 2
      weeks after delivery when the osteopenia was still severe. Healing of the
      fracture followed with recovery of hip movements.

PMID- 9266304
TI  - The role of shoulder fusion in the era of arthroplasty.
AB  - The indications, surgical techniques, results and complications of shoulder
      fusion are described. The indications are bacterial infection, paralytic
      disorders in infancy, combined deltoid and rotator cuff paralysis, post-traumatic
      brachial plexus lesions, inflammatory arthritis with severe rotator cuff
      involvement, failed arthroplasty, recurrent dislocation, after resection of
      tumours, irreparable rotator cuff tear, painful arthritis in a patient whose
      activities require power but not movement, the immunocompromised patient, and
      tuberculosis. Satisfactory results are achieved in children with isolated
      shoulder paralysis, but in adults loss of glenohumeral movement is associated
      with about 50% loss of function. The best results are obtained in cases of
      isolated shoulder paralysis with a normal arm and hand distally. The most
      frequent complications are nonunion (5-20%), fracture of the ipsilateral humerus
      (10-15%) and infection (3-5%). Other causes of failure are functional limitation,
      fusion in malposition, functional involvement of the distal joints,
      acromioclavicular dislocation, suprascapular traction neuritis, failure or
      migration of an internal fixation device, epiphyseal problems, and the
      complications of using an allograft. Shoulder replacement is most likely to be
      chosen for most destructive shoulder disorders, but fusion is useful in certain
      cases.

PMID- 9266305
TI  - Molecular basis of functional diversity of ATP-sensitive K+ channels.

PMID- 9266306
TI  - Molecular aspects of ATP-sensitive K+ channels in the cardiovascular system.

PMID- 9266307
TI  - Free-radical mediated cellular regulation in pancreatic beta-cells.

PMID- 9266308
TI  - Ionic and metabolic messengers in the control of insulin secretion.

PMID- 9266309
TI  - Expression of uKATP-1 (Kir6.1) in neonatal rat kidney proximal tubule.

PMID- 9266310
TI  - Regulation of glucose metabolism and opening of K(ATP) channels in pancreatic
      beta-cells by NO.

PMID- 9266311
TI  - GLP-1 (7-36) amide activates L-type Ca2+ channels of pancreatic B-cells through c
      AMP signaling.

PMID- 9266312
TI  - Radical production and degranulation in pancreatic islets induced by glucose.

PMID- 9266313
TI  - Coordination in oscillatory Ca2+ signalling in endocrine and exocrine pancreas.

PMID- 9266314
TI  - The endoplasmic reticulum membrane: ion channels and changes in membrane
      capacitance.

PMID- 9266316
TI  - Components of insulin secretion: lessons to be learnt from capacitance.

PMID- 9266315
TI  - Volume-sensitive Cl- channel in human epithelial cells: regulation by ATP and
      relation to P-glycoprotein.

PMID- 9266317
TI  - Glucose stimulation of insulin release without an increase in cytosolic free Ca2+
      concentration: a possible involvement of GTP.

PMID- 9266318
TI  - Analysis of the secretory granule movement in the pancreatic beta-cell:
      regulation by intracellular messengers.

PMID- 9266319
TI  - Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates insulin
      secretion in islets and potentiates glucose-transport in adipocytes.

PMID- 9266320
TI  - The role of Ca2+ in the glucagon-induced enhancement of electrical activity of
      pancreatic beta-cells.

PMID- 9266321
TI  - Glucose transport and energy metabolism regulated by brain histamine.

PMID- 9266322
TI  - Protein tyrosine phosphatases as stimulators and inhibitors of insulin
      signalling: possible candidates for insulin resistance.

PMID- 9266323
TI  - Glucose sensors in the medulla oblongata.

PMID- 9266325
TI  - The effect of glucose and other sugars on the efferent activity of the
      sympathetic nerves innervating the fatty tissue.

PMID- 9266326
TI  - Reversible translocation of glucokinase between the nucleus and the cytoplasm in
      rat hepatocytes.

PMID- 9266324
TI  - Cell biology of insulin action on glucose transport.

PMID- 9266328
TI  - Molecular mechanism of insulin-stimulated glucose transport in 3T3-L1 adipocytes.

PMID- 9266327
TI  - Adrenergic and purinergic receptors-mediated calcium responses in brown
      adipocytes.

PMID- 9266329
TI  - Functional interaction between Na(+)-K+ pump and KATP channels in the CNS neurons
      under experimental brain ischemia.

PMID- 9266330
TI  - aFGF, endogenous satiety substance, facilitates learning, memory and immune
      function in aging.
AB  - aFGF injection s.c. once a week into SAMP8 was begun at 3 weeks after birth and
      continued for 10 months. Saline was injected as a control. learning and memory
      and cellular immunological functions in the aFGF group were enhanced
      significantly, while those of the saline group deteriorated. 1. The number of
      cholinergic neurons was decreased by less than 20% and ChAT activity in
      individual neurons in the medial septum which send monosyonaptic terminals to the
      hippocampus was significantly decreased in the saline group, but not so much in
      the aFGF group. 2. The respective densities of muscarinic and aFGF receptors, on
      the hippocampal neurons were significantly higher in the aFGF group than in the
      saline group. 3. The LTP in hippocampal slice preparations was significantly
      facilitated in the aFGF group, but not in the saline group. 4. The DTH, (T cell
      immune response) measured at the end of the 2nd and 7th months were reduced in
      the 7th month as compared with the 2nd month in the saline group, but aFGF group
      protected against this reduction. 5. These results show that aFGF provides
      protection against impairment of not only learning and memory but also the DTH
      immunoreactivity in SAMP8.

PMID- 9266331
TI  - Substrate binding sites of glutamate transporters and structurally related
      neutral amino acid transporters.

PMID- 9266332
TI  - Voltage dependence of Na+/K(+)-ATPase: structural implications.

PMID- 9266333
TI  - Characterization of organic ion transporters involved in renal excretion of
      xenobiotics.

PMID- 9266334
TI  - Role of calcium ions in the potentiation by isoproterenol of carbachol-induced
      ionic currents and secretion activity in rat salivary glands.

PMID- 9266335
TI  - Purinergic and mechanical interactions between myo- and secretory epithelial
      cells in mammary gland.

PMID- 9266336
TI  - Insulin-regulation of single chloride channel conductance via protein phosphatase
      2B-dependent pathway.

PMID- 9266337
TI  - Enantiospecific inhibition of ligature-induced periodontitis in beagles with
      topical (S)-ketoprofen.
AB  - Systemic and topical administration of non-steroidal anti-inflammatory drugs
      (NSAIDs) has been shown to reduce periodontal disease progression in both animal
      models and human subjects. Our present research focuses on single enantiomers of
      these agents to examine whether enantiospecific therapy will be efficacious in
      slowing periodontitis. The purpose of this study was to evaluate the inhibitory
      effects of (S)-ketoprofen on experimentally induced alveolar bone loss in beagle
      dogs. 16, 18-month-old, female beagles were brought to optimal periodontal health
      over a 2-week pretreatment period. Experimental periodontitis was then induced by
      placing silk ligatures around premolar and molar teeth and by instituting a soft,
      plaque-promoting diet. At baseline, animals were randomized to 1 of 4 groups,
      consisting of 2x daily administration of (1) placebo dentifrice, (2) 0.3% (S)
      ketoprofen dentifrice, (3) 3.0% (S)-ketoprofen dentifrice, or (4) 10.0 mg (S)
      ketoprofen capsules (p.o.) over a 60 day treatment period. Standardized,
      periapical radiographs exposed at days 1 and 60 were analyzed by computer
      assisted digital radiography in order to assess the rate of alveolar bone loss.
      Secondary outcomes included technetium 99m-tin-diphosphonate (99mTc-Sn-MDP)
      uptake and the gingival index. At baseline, no differences were observed among
      the groups for linear bone height or 99mTc-Sn-MDP uptake ratios. From days 1 to
      60, cohorts differed significantly in terms of bone loss rates (p < 0.001). In
      particular, beagles treated with systemic or topical (S)-ketoprofen (0.3% or 3.0%
      dentifrices) exhibited significantly lower mean rates of bone loss compared to
      placebo treated beagles (p < 0.05). Group differences in mean radiopharmaceutical
      uptake ratio changes approached significance (ANOVA, p = 0.07), where animals
      treated with topical 0.3% (S)-ketoprofen demonstrated a reduction and other
      groups demonstrated elevations over the 60-day dosing period. Treatment cohorts
      did differ significantly with respect to changes in mean gingival indices (p <
      0.05). Animals treated with 0.3% or 3.0% (S)-ketoprofen dentifrice exhibited
      significantly reduced elevations in gingival index scores as compared to placebo
      treated animals. These data provide evidence that enantiospecific therapy with
      (S)-ketoprofen, topically or systemically delivered, may alter the progression of
      periodontal disease in the beagle dog model.

PMID- 9266338
TI  - Healing response of gingival recession defects following guided tissue
      regeneration procedures in smokers and non-smokers.
AB  - This retrospective study evaluated healing response in gingival recession defects
      following guided tissue regeneration (GTR) in smokers. 22 systemically healthy
      patients who had been treated for deep (> or = 4 mm), buccal, Miller's class I or
      II gingival recession defects with ePTFE membranes were included. Patients were
      regarded as smokers if they smoked more than 10 cigarettes/day at the time of
      surgical procedure. Occasional and former smokers were excluded. 9 patients (6
      male, mean age 29 years) were smokers, while 13 patients (4 male, mean age 35
      years) were non-smokers. Clinical parameters, recorded presurgery and at 6 months
      postsurgery, included defect-specific plaque (DP1) and bleeding on probing (BoP)
      scores, recession depth (RD), probing depth (PD), clinical attachment level
      (CAL), and keratinized tissue width (KG). Extent of membrane exposure (ME) and
      newly formed tissue (NFT) gain were assessed at membrane removal. Statistical
      analysis revealed no significant differences between smokers and non-smokers in
      demographic and presurgery defect characteristics. DP1 and BoP scores were
      similar presurgery and remained almost unchanged throughout the observation
      interval in both groups. ME was significantly greater in smokers (2.6 +/- 1.4 mm)
      than in non-smokers (1.3 +/- 0.6 mm). NFT gain was 2.8 +/- 1.0 mm in smokers and
      3.6 +/- 1.4 mm in non-smokers, the difference being not statistically
      significant. Smokers showed significantly less RD reduction and root coverage
      (2.5 +/- 1.2 mm and 57%, respectively) compared to non-smokers (3.6 +/- 1.1 mm
      and 78%, respectively). In conclusion, the results indicate that treatment
      outcome following GTR in gingival recession defects is impaired in cigarette
      smokers.

PMID- 9266339
TI  - Effect of different concentrations of EDTA on smear removal and collagen exposure
      in periodontitis-affected root surfaces.
AB  - The purpose of the present study was to explore the possibility of obtaining an
      acceptable smear-removing and collagen-exposing effect following EDTA etching
      with concentrations lower than supersaturation (24%). A flat dentin surface was
      created on human teeth extracted due to severe periodontitis. The teeth were
      etched with the following concentrations of EDTA for 2 min: 1.5% (group I), 5%
      (group II), 15% (group III) and 24% (group IV), and evaluated with scanning
      electron microscopy with respect to smear layer removal and exposure of root
      associated collagen fibers. It was found that neither 1.5% nor 5% EDTA etching
      was sufficient to dissolve the smear layer to any higher degree. Etching with 15%
      EDTA dissolved the smear more effectively than the lower concentrations and
      collagen fibers were sparsely found. Following etching with 24% EDTA (group IV),
      significantly less smear was seen on the dentin surfaces than in any of the other
      groups and collagen fibers were seen covering the entire intertubular dentin
      surfaces. Based on these findings, the concentration of EDTA should be somewhere
      between 15 to 24% in order to obtain an acceptable smear removing and collagen
      exposing effect within a clinically acceptable time period.

PMID- 9266340
TI  - beta-Lactamase producing bacteria in adult periodontitis.
AB  - In 23 untreated adult periodontitis patients, the occurrence of beta-lactamase
      producing periodontal bacteria was determined. In addition to non-selective
      isolation media, selective isolation and growth of beta-lactamase positive
      subgingival bacterial species was carried out on blood agar plates supplemented
      with amoxicillin and plates with amoxicillin+clavulanic acid. Porphyromonas
      gingivalis, Prevotella intermedia, Actinobacillus actinomycetemcomitans,
      Peptostreptococcus micros, Fusobacterium nucleatum, Bacteroides forsythus and
      Campylobacter rectus isolates from the non-selective medium were tested for beta
      lactamase activity by a nitrocefin disk method (DrySlide) and by a laboratory
      chromogenic nitrocefin-based test. Isolates from the amoxicillin plates that were
      absent on the amoxicillin/clavulanic acid plates were identified and tested for
      beta-lactamase production. Based on the non-selective plates, six of 23 P.
      intermedia isolates, 2 of 19 B. forsythus isolates and 3 of 23 F. nucleatum
      isolates were beta-lactamase positive. The beta-lactamase positive species
      Prevotella loescheii, Prevotella buccae, Prevotella buccalis and Actinomyces spp
      were recovered from the selective amoxicillin plates. beta-Lactamase positive
      subgingival species were recovered from 17 of 23 patients (74%) but usually
      comprised low proportions of the subgingival microbiota (range < 0.01-15%).
      Comparison of the DrySlide test and the nitrocefin-based laboratory test revealed
      full agreement of test results. beta-Lactamase activity in whole subgingival
      plaque was detected in 12 patient samples (52%). It was concluded that beta
      lactamase activity in subgingival bacteria in adult periodontitis is a common
      feature. However, since the majority of the samples showed only low-level
      enzymatic activity, the clinical relevance of this observation with regard to
      therapy with unprotected enzyme-susceptible beta-lactams is uncertain, though
      failure on the other hand, is difficult to rule out when a mechanism of
      resistance is present. The majority of beta-lactamase positive strains was found
      among species of the Prevotella genus.

PMID- 9266341
TI  - Guided tissue regeneration using a collagen membrane in chronic adult and rapidly
      progressive periodontitis patients in the treatment of 3-wall intrabony defects.
AB  - This study, confined to non-smokers, evaluated guided tissue regeneration using a
      diphenylphosphorylazide-cross-linked bovine type I collagen membrane in deep 3
      wall intrabony defects in 52 adult periodontitis (AP) and 16-rapidly progressive
      periodontitis (RPP) patients, previously treated for the acute phase of the
      disease, no more than one defect being randomly selected for each patient. Before
      surgery and 6 months after surgery, plaque (PI) and sulcus bleeding (SBI)
      indices, as well as probing pocket depths (PPD), gingival margin locations (GML)
      and probing attachment levels (PAL) were recorded. During the post-surgical
      period, the membranes were very well tolerated in all patients and PI and SBI
      were kept at a low level. 6 months post-surgical, there was a significant gain in
      PAL (3.6 mm for AP; 2.6 mm for RPP) and reduction in PPD (5.5 mm for AP; 4.1 mm
      for RPP) for both groups of patients (p < 0.05). However, neither the change in
      GML (1.9 mm for AP; 1.5 mm for RPP), nor PPD or PAL yielded a statistically
      significant difference between AP and RPP patients. The results of this study
      demonstrated that the treatment of deep 3-wall intrabony defects with a
      diphenylphosphorylazide-cross-linked collagen membrane in both AP and RPP
      patients during the quiescent phase of the disease is a treatment modality where
      the conquences are predictable. However, longer observation periods are necessary
      to evaluate the stability of the improvements obtained for the 2 groups of
      patients and the differences between them.

PMID- 9266343
TI  - Selection of the most accurate method of conventional radiography for the
      assessment of periodontal osseous destruction.
AB  - The purpose of the present study was to compare the radiographic measurements of
      periodontal osseous destruction with the surgical measurements, which represent
      the true value of osseous destruction, and to select the most successful method
      of conventional radiography in detecting and accurately assessing periodontal
      osseous destruction. A total of 5072 proximal surfaces in 2536 teeth of 100
      patients with periodontitis were evaluated surgically during periodontal flap
      surgery and radiographically by using periapical and panoramic radiography.
      Comparative evaluation of the measurements obtained by these 3 different methods
      of osseous destruction assessment revealed the following. (1) The radiographic
      detection ability of small osseous destruction (1-4 mm) was very low for both
      methods of assessment and became even lower for the initial osseous destruction
      (1 or 2 mm). (2) Periapical radiography was more successful than panoramic in the
      detection of osseous destruction, especially of the small destruction (4.7x). (3)
      Panoramic radiography underestimated the osseous destruction, whereas periapical
      radiography was relatively accurate in the osseous destruction assessment. (4)
      Periapical radiography was more accurate in the osseous destruction assessment
      than panoramic, regardless of the location of the dental surfaces (jaw, tooth
      group, mesial or distal) and the degree of osseous destruction. (5) The deviation
      of the radiographic measurements of osseous destruction from the surgical
      measurements, as well as the difference between the two radiographic methods,
      depended on the jaw location, the tooth group and the degree of osseous
      destruction. (6) The radiographic assessment of osseous destruction
      underestimated the osseous destruction in initial periodontitis, it was
      relatively accurate in moderate periodontitis, but overestimated it in severe
      periodontitis. The radiographic measurements of osseous destruction deviated
      least from the surgical measurements in the group of moderate periodontitis and
      most in that of severe osseous destruction. (7) The 2 radiographic methods agreed
      most in the assessment of osseous destruction in the severe periodontitis group
      and least in the initial periodontitis group. (8) The indirect Schei method was
      less successful in detecting the small osseous destruction and less accurate in
      assessing the osseous destruction than the direct millimetric method of
      radiographic evaluation. (9) The osseous destruction as assessed from periapical
      radiographs by the Schei method was not significantly different from that
      assessed by the radiopaque Fixot-Everett grid. The results of the present study
      suggest that periapical radiography is more successful in detecting periodontal
      osseous destruction and more accurate in assessing it than panoramic radiography.

PMID- 9266342
TI  - Combined collagen membrane and hydroxyapatite/collagen chondroitin-sulfate spacer
      placement in the treatment of 2-wall intrabony defects in chronic adult and
      rapidly progressive periodontitis patients.
AB  - This study, confined to non-smokers, evaluated guided-tissue regeneration in deep
      2-wall intrabony defects using a diphenylphosphorylazide-cross-linked bovine type
      I collagen membrane supported by a hydroxyapatite/collagen/chondroitin-sulfate
      spacer in 43 adult periodontitis (AP) and 14 rapidly progressive periodontitis
      (RPP) patients, no more than 1 defect being randomly selected for each patient.
      Before surgery and 6 months after surgery, plaque (PI) and sulcus bleeding (SBI)
      indices, probing pocket depths (PPD), gingival margin locations (GML) and probing
      attachment levels (PAL) were recorded. During the post-surgical period, the
      biomaterials were well tolerated in all patients and PI and SBI were kept at a
      low level. Following therapy, there was a significant gain in PAL (4.2 mm for AP;
      3 mm for RPP) and reduction in PPD (6.1 mm for AP; 4.7 mm for RPP) for both
      groups of patients (p < 0.05). A significantly greater gain in PAL and reduction
      in PPD were observed for AP compared to RPP patients (p < 0.05). The change in
      GML was not statistically different between groups (1.8 mm for AP; 1.6 mm for
      RPP). It is concluded that the combined use of a diphenylphosphorylazide-cross
      linked bovine type-I collagen membrane, supported by a
      hydroxyapatite/collagen/chondroitin-sulfate spacer, is beneficial in improving
      PAL and reducing PPD in 2-wall intrabony defects in both AP and RPP patients
      during the quiescent phase of the disease, with statistically better results for
      the former group. However, longer observation periods are necessary to evaluate
      the stability of the improvements obtained by this combined treatment approach
      between and for each group of patients.

PMID- 9266344
TI  - The mucosal barrier following abutment dis/reconnection. An experimental study in
      dogs.
AB  - In the present experiment, the effect on the marginal peri-implant tissues
      following repeated abutment removal and subsequent reconnection was studied. 5
      beagle dogs were used. The mandibular premolars were extracted and 2 fixtures of
      the Branemark System were installed, 1 in each mandibular quadrant. 3 months
      later, abutment connection was performed. A 6-month period of plaque control was
      initiated. Once a month during the plaque control period, the abutment of the
      right side (test) in each dog was disconnected, cleaned and reconnected to the
      failure. Thus, each test abutment was removed and reconnected altogether 5x
      during this period. The contralateral abutment remained undisturbed for 6 months
      and served as control. 1 month after the last reconnection, the animals were
      sacrificed and tissue samples, comprising the implant and the surrounding soft
      and hard peri-implant tissues, were obtained, decalcified, embedded in Epon and
      sectioned. The following landmarks were identified and used for linear
      measurements: PM (the marginal portion of the peri-implant mucosa), aJE (the
      level of the apical termination of the junctional epithelium), B (the marginal
      level of bone to implant contact), A/F (the abutment/fixture border). The
      findings indicate that the dis- and subsequent reconnections of the abutment
      component of the implant compromised the mucosal barrier and resulted in a more
      "apically" positioned zone of connective tissue. The additional marginal bone
      resorption observed at the test sites following abutment manipulation may be the
      result of tissue reactions initiated to establish a proper "biological width" of
      the mucosal-implant barrier.

PMID- 9266345
TI  - Effects of metronidazole in patients with "refractory" periodontitis associated
      with Bacteroides forsythus.
AB  - The aim of the present study was to monitor the microbiological and clinical
      effects of renewed supra- and subgingival debridement in conjunction with
      systemic metronidazole therapy (500 mg TID for 7 days) in 27 "refractory"
      periodontitis patients, culture positive for Bacteroides forsythus and negative
      for Actinobacillus actinomycetemcomitans. Clinical evaluation included assessment
      of plaque, bleeding upon probing, probing pocket depth and clinical attachment
      loss at the deepest, bleeding site in each quadrant. Microbiological evaluation
      was carried out by anaerobic cultivation of subgingival plaque samples from the
      same sites. 6 months after renewed debridement and systemic metronidazole (RD+M),
      a statistically significant improvement of all clinical parameters was observed,
      except for the plaque index. After RD+M, B. forsythus was suppressed below
      detection level in 17 of the 27 patients, P. gingivalis in 9 out of 15 patients
      and P. intermedia in 14 of the 21 patients. Before RD+M, 12 patients harboured
      simultaneously B. forsythus, P. gingivalis as well as P. intermedia. Out of
      these, 6 patients were culture negative for the 3 species after therapy and
      showed the greatest reduction in pocket depth (3.1 mm) and gain of clinical
      attachment level (2.5 mm). In the treatment of refractory periodontitis,
      associated with patients culture positive for B. forsythus and negative for A.
      actinomycetemcomitans, metronidazole can significantly improve the clinical and
      microbiological parameters.

PMID- 9266346
TI  - Is there an association between periodontal condition and HIV infection?
AB  - Individuals in Tanzania who have limited access to medical and dental treatment
      provide an opportunity to study the natural association between periodontal
      condition and HIV infection and the stage of infection. 119 HIV-infected adult
      individuals and 73 individuals with AIDS from the AIDS Clinical Trial Clinic at
      Muhimbili Medical Centre (MMC) in Dar-es-Salaam participated as cases. Mean age
      was 35.3 and 35.1 years, respectively. 156 individuals with a mean age of 28.3
      years, confirmed as HIV-seronegative, served as controls. There were no
      significant differences in bleeding on probing, pocket formation or attachment
      loss among the HIV-seronegative individuals, HIV-seropositive and AIDS patients.
      We applied multiple logistic regression to calculate odds ratios for presence of
      periodontal conditions adjusting for age, gender and DMFT. Our odds ratios did
      not reveal any significant associations between bleeding on probing, pocket
      formation or attachment loss with regard to lymphocyte and CD4+ T-cell counts
      among the HIV-infected individuals and AIDS patients. When associations were
      investigated with regard to HIV-serostatus (HIV-seronegative, HIV-seropositive or
      AIDS), our adjusted odds ratios were insignificant, too. In fact, most odds
      ratios were close to 1. Thus, our study supports recent views that the presence,
      extent and severity of periodontal disease among HIV-infected individuals, may be
      less that hitherto thought.

PMID- 9266347
TI  - Urinary uracil concentrations are a useful guide to genetic disorders associated
      with neurological deficits and abnormal pyrimidine metabolism.

PMID- 9266348
TI  - The activity of dihydropyrimidine dehydrogenase in human blood cells.

PMID- 9266349
TI  - Identification of novel point mutations in the dihydropyrimidine dehydrogenase
      gene.

PMID- 9266350
TI  - Dihydropyrimidinase deficiency: confirmation of the enzyme defect in
      dihydropyrimidinuria.

PMID- 9266351
TI  - Adenylosuccinase deficiency: clinical and biochemical findings in 5 Czech
      patients.

PMID- 9266352
TI  - 1H NMR spectroscopy of body fluids in patients with inborn errors of purine and
      pyrimidine metabolism.

PMID- 9266353
TI  - Familial renal disease or familial juvenile hyperuricaemic nephropathy?

PMID- 9266354
TI  - Benign persistent orotic aciduria and the possibility of misdiagnosis of
      ornithine carbamoyltransferase deficiency.

PMID- 9266355
TI  - Hyperhomocysteinemia--a risk factor for abruptio placentae.

PMID- 9266356
TI  - Analysis of CBS alleles in Czech and Slovak patients with homocystinuria: report
      on three novel mutations E176K, W409X and 1223 + 37 del99.

PMID- 9266357
TI  - Complete reversal of moderate/severe brain MRI abnormalities in a patient with
      classical phenylketonuria.

PMID- 9266358
TI  - Differing clinical presentation of succinic semialdehyde dehydrogenase deficiency
      in adolescent siblings from Lifu Island, New Caledonia.

PMID- 9266359
TI  - Reversible dysregulation of the mitochondrial ATP synthase in skin fibroblasts
      from children with vitamin B12-dependent methylmalonic acidaemia.

PMID- 9266360
TI  - Inhibition of beta-ureidopropionase by propionate may contribute to the
      neurological complications in patients with propionic acidaemia.

PMID- 9266361
TI  - Compound heterozygosity in the glutaryl-CoA dehydrogenase gene with R227P
      mutation in one allele is associated with no or very low free glutarate
      excretion.

PMID- 9266363
TI  - Mevalonate kinase deficiency in a dizygotic twin with mild mevalonic aciduria.

PMID- 9266362
TI  - Nerve cell lesions caused by 3-hydroxyglutaric acid: a possible mechanism for
      neurodegeneration in glutaric acidaemia I.

PMID- 9266364
TI  - D-(+)-glyceric aciduria in an Afghan hound.

PMID- 9266365
TI  - Valproate inhibits the mitochondrial pyruvate-driven oxidative phosphorylation in
      vitro.

PMID- 9266366
TI  - A case of benign pyruvate carboxylase deficiency with normal development.

PMID- 9266367
TI  - Muscle biochemistry in thiamin-responsive anaemia.

PMID- 9266368
TI  - Hypoketonuric 3-hydroxydicarboxylic aciduria in five patients with glycogen
      storage disease.

PMID- 9266369
TI  - Diagnosis of inborn errors of metabolism by acylcarnitine profiling in blood
      using tandem mass spectrometry.

PMID- 9266370
TI  - Improved detection of long-chain fatty acid oxidation defects in intact cells
      using [9,10-3H]oleic acid.

PMID- 9266371
TI  - Molecular basis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency:
      identification of two new mutations.

PMID- 9266372
TI  - Broad specificity of carnitine palmitoyltransferase II towards long-chain acyl
      CoA beta-oxidation intermediates and its practical approach to the synthesis of
      various long-chain acylcarnitines.

PMID- 9266373
TI  - Short-chain acyl-CoA dehydrogenase deficiency in a 16-year-old girl with severe
      muscle wasting and scoliosis.

PMID- 9266374
TI  - Smith-Lemli-Opitz syndrome: deficient delta 7-reductase activity in cultured skin
      fibroblasts and chorionic villus fibroblasts and its application to pre- and
      postnatal detection.

PMID- 9266375
TI  - Genetic heterogeneity in patients with a disorder of peroxisomal beta-oxidation:
      a complementation study based on pristanic acid beta-oxidation suggesting
      different enzyme defects.

PMID- 9266376
TI  - Formation of 2,3-pristenic acid and 3-hydroxypristanic acid from pristanic acid
      in human liver.

PMID- 9266377
TI  - Phytanoyl-CoA hydroxylase is not only deficient in classical Refsum disease but
      also in rhizomelic chondrodysplasia punctata.

PMID- 9266378
TI  - Phosphomannomutase deficiency is the main cause of carbohydrate-deficient
      glycoprotein syndrome with type I isoelectrofocusing pattern of serum
      sialotransferrins.

PMID- 9266379
TI  - GC-MS determination of guanidinoacetate in urine and plasma.

PMID- 9266380
TI  - Molecular analysis in 23 Hunter disease families.

PMID- 9266381
TI  - Polyunsaturated fatty acids reverse the lysosomal storage and accumulation of
      subunit 9 of mitochondrial F1F0-ATP synthase in cultured lymphoblasts from
      patients with Batten disease.

PMID- 9266382
TI  - Continuous venovenous haemodiafiltration in the acute phase of neonatal maple
      syrup urine disease.
AB  - Maple syrup urine disease results in accumulation of leucine and its metabolites,
      which may lead in the long term to neurological dysfunction. In acute neonatal
      crises, large amounts of leucine may be removed by continuous venovenous
      haemofiltration. This extracorporeal technique has its risks and hazards, which
      increase with duration of treatment. We report three neonates in life-threatening
      conditions due to maple syrup urine disease, treated for not more than 12 h with
      various continuous venovenous techniques: continuous haemofiltration,
      haemodiafiltration and haemodialysis. The efficiency of and tolerance to these
      techniques was evaluated. For all three patients, plasma leucine levels decreased
      dramatically from 2186, 3818 and 2536 mumol/L to 1131, 1275 and 488 mumol/L,
      respectively. Leucine clearance obtained was 4.28 ml/min in haemodiafiltration.
      Their patients' neurological status improved rapidly and they have a normal
      developmental quotient at 22 months, 13 months, and 11 months of age,
      respectively. Tolerance was good except for hypothermia and drop in haematocrit
      in all cases. Haemodiafiltration management was more cumbersome and time
      consuming because it required continual adjustment of the substitution fluid flow
      rate to precisely balance inflow and outflow rates. We recommend continuous
      venovenous haemodialysis as the therapy of choice. It might be anticipated that
      improvement of this technique, by increasing dialysate flow rate and blood flow
      rate, will allow leucine concentration to be decreased below 1000 mumol/L within
      6-8 h, whatever the initial level.

PMID- 9266383
TI  - Abnormal glutathione conjugation in patients with tyrosinaemia type I.
AB  - Previous studies have suggested that tyrosinaemia type I may be associated with
      reduced glutathione availability due to conjugation of tyrosinaemia-associated
      reactive intermediates with glutathione. In the present study, the glutathione/
      glutathione S-transferase system of two tyrosinaemia patients and three healthy
      controls were characterized by administering the racemic sedative drug
      bromisoval, a probe drug for assessing glutathione conjugation activity in vivo.
      Furthermore, concentrations of glutathione and glutathione S-transferase class
      alpha (GSTA) isoenzymes as well as the glutathione S-transferase class mu
      phenotype were assessed in the blood of six tyrosinaemia patients. The excretion
      of bromisoval mercapturates in healthy children was comparable to that observed
      in healthy adults. Tyrosinaemia patients were found to have a very high urinary
      recovery of bromisoval mercapturates (> or = 60% of the dose compared to about
      30% for healthy, age-matched children and adults), which could be attributed
      mainly to a higher urinary excretion of the mercapturate derived from S
      bromisoval. Healthy children and adults predominantly excrete the (R)-bromisoval
      mercapturate. The differences in amount excreted as well as in stereoselectivity
      of the urinary excretion of bromisoval mercapturates in tyrosinaemia patients are
      possibly related to an increased activity of specific glutathione S-transferase
      isoenzymes. Plasma glutathione and blood cell glutathione disulphide
      concentrations in tyrosinaemia patients were normal. Low blood cell glutathione
      concentrations were in general found only in two patients with a poor clinical
      condition. These results indicate that, in contrast to previous suggestions,
      reduced glutathione availability is not a generalized problem in (stabilized)
      tyrosinaemia patients.

PMID- 9266384
TI  - Treatment products and approaches for phenylketonuria: improved palatability and
      flexibility demonstrate safety, efficacy and acceptance in US clinical trials.
AB  - A new amino acid formulation and a variety of treatment products incorporating it
      were evaluated for long-term safety, efficacy, and acceptance in 25 subjects with
      phenylketonuria over a period of 5 years. Palatability of the treatment was
      improved by reducing the required intake of amino acids, reformulating the
      mixture to have better taste, and providing vitamins and minerals as tablets. The
      hypotheses were that these strategies would improve compliance and metabolic
      control and maintain nutritional status in subjects. Compliance with treatment
      was determined from mean reported intakes (4-day diet records) and from mean
      'received' intakes using receipts of treatment products actually shipped to
      individuals upon request. Mean amino acid intakes prescribed were significantly
      reduced from study entry to end, from 1.2 g/kg to 0.7 g/kg (p < 0.001). Reported
      intakes were similarly reduced from 1.3 g/kg to 0.7 g/kg (p < 0.001). While
      actually 'received' intakes of amino acid formula were also significantly reduced
      (p < 0.001), intakes by this measure were much lower than either prescribed or
      reported, 0.9 g/kg at entry and 0.4 g/kg at the end of the study, suggesting that
      acceptance of the treatment (usage of products), even when made more palatable,
      is below clinical expectations. In spite of these findings, mean serum proteins
      and minerals, height and weight were not significantly reduced during the study,
      supporting the safety of lowered intakes of amino acids and of nutritionally
      incomplete products. While the increase in mean serum phenylalanine concentration
      from 0.38 to 0.48 mmol/L was significant (p < 0.03), this mean rise of 0.1 mmol/L
      during a corresponding mean age increase of 4.2 years (from 6.9 to 11.1 years) is
      lower than in other recent reports from longitudinal studies of outcomes during
      this age range in subjects treated with traditional products. These data support
      the safety and efficacy of a more palatable and flexible approach to treatment.

PMID- 9266385
TI  - Adult psychosocial outcome in early-treated phenylketonuria.
AB  - Concerns about the psychosocial risk of adults with early-treated phenylketonuria
      (ETPKU) are predicated on four sources of scientific data: (1) consistent
      documentation of increased behavioural risk in children with ETPKU; (2) recent
      evidence of neurocognitive impairment in adults with ETPKU; (3) reports of
      neuroimaging abnormalities in adults with ETPKU; and (4) preliminary evidence of
      increased rates of psychiatric disturbance in this population. We studied the
      psychosocial adjustment of 25 patients, aged 18 years and older, with ETPKU. On
      most psychosocial outcome measures, patients were indistinguishable from 15
      sibling controls. However, on a self-report inventory of psychiatric symptoms,
      20% of the patients demonstrated significant morbidity. Psychosocial outcome of
      these patients was unrelated to concurrent or historical biological dietary
      disease factors, unlike neurocognitive outcome. A strong relationship was
      demonstrated, however, between neurocognitive measures and psychosocial
      morbidity. These findings indicate that a significant minority of patients with
      ETPKU develop psychosocial difficulties with multiple clinical elevations on a
      psychiatric inventory. However, most adults with ETPKU cope with the challenges
      of young adulthood with the same degree of success as their unaffected siblings.
      Neuropsychological surveillance during childhood and adolescence is important in
      identifying patients at risk for both neurocognitive and psychosocial morbidity.

PMID- 9266386
TI  - Mitochondrial abnormalities of liver in two children with citrullinaemia.
AB  - Citrullinaemia is a rare inborn error of urea-cycle metabolism. Two affected
      children are reported in whom progressive metabolic instability suggested the
      possibility of hepatopathy or an ongoing hepatic mitochondrial injury. A
      percutaneous liver biopsy was performed in each patient. Electron-microscopic
      findings were similar in both cases. Approximately 20% of the mitochondria were
      abnormally enlarged with paracrystalline inclusions and electron-dense bodies of
      different sizes and shapes present in the matrix. The specificity of these
      findings is discussed in the context of previous reports of ultrastructural
      abnormalities in the hepatocytes of patients with inborn errors of the urea
      cycle. It is speculated that the mitochondrial abnormalities in citrullinaemia
      may be related to the accumulation of citrulline in the mitochondria which may
      eventually manifest as metabolic instability.

PMID- 9266387
TI  - Mutation of ornithine transcarbamylase (H136R) in a girl with severe intermittent
      orotic aciduria but normal enzyme activity.
AB  - Ornithine transcarbamylase deficiency shows X-linked inheritance with partial
      dominant expression in carrier females. We studied a girl with intermittent
      severe orotic aciduria and mild hyperammonaemia despite apparently normal enzyme
      activity in the liver. Sequence analysis of all 10 exons of the ornithine
      transcarbamylase gene revealed a novel A-->G exchange (A502G) in exon 5 which
      changes His-136 to arginine in the ornithine transcarbamylase protein. Km values
      for carbamyl phosphate and ornithine determined in the patient's liver were
      comparable to those of wild-type enzyme but, unlike the wild-type enzyme, the
      mutant enzyme was unstable upon freezing and thawing. Electron microscopy
      revealed several giant mitochondria with paracrystalline inclusions. The results
      are compatible with the assumption that the mutant enzyme cannot form a
      functional complex with carbamyl phosphate synthetase and the ornithine carrier,
      resulting in decreased availability of substrates and diminished enzyme activity
      in vivo.

PMID- 9266388
TI  - Identification of 'private' mutations in patients with ornithine transcarbamylase
      deficiency.
AB  - The majority of cases of ornithine transcarbamylase deficiency are due to novel
      mutations making it impossible to develop common methods for genetic analysis.
      However, identification of causative mutations has important implications for
      diagnosis (particularly prenatal diagnosis), prediction of likely course and
      outcome and the eventual possibility of gene therapy. As part of a continuing
      study of ornithine transcarbamylase deficiency, we now report an additional
      thirty novel mutations in the ornithine transcarbamylase gene, together with a
      brief summary of their clinical presentations.

PMID- 9266389
TI  - Clinical heterogeneity and prognosis in combined methylmalonic aciduria and
      homocystinuria (cblC).
AB  - The clbC form of methylmalonic acidaemia is a rare and poorly understood
      condition which results from impaired biosynthesis of methylcobalamin and
      adenosylcobalamin. The consequent functional deficiencies of methylmalonyl-CoA
      mutase and methionine synthase produce both methylmalonic aciduria and
      homocystinuria. Systemic symptoms and neurological decompensation comprise the
      clinical phenotype. In an effort to clarify the phenotype and prognosis, we
      obtained clinical information on 50 patients with methylmalonic acidaemia whose
      cells had been assigned to the cblC complementation group. We identified two
      distinct phenotypes; they differed in age of onset, presence of systemic
      symptoms, type of neurological symptoms, and outcome after diagnosis and
      treatment. Forty-four patients presented in the first year of life. Feeding
      difficulties, neurological dysfunction (hypotonia, seizures, developmental
      delay), and ophthalmological and haematological abnormalities characterized their
      clinical picture. About one-quarter of those patients died. Survival was
      associated with neurological impairment; only one infant was neurologically
      intact at follow-up. Onset in childhood, in contrast, was associated with less
      severe haematological abnormalities, largely involving the red cell series.
      Extrapyramidal signs, dementia, delirium or psychosis characterized the
      neurological findings. Survival, with mild to moderate disability in some, was
      typical in patients with later onset. Treatment in both groups included
      hydroxycobalamin, betaine and carnitine; complete normalization of biochemical
      parameters was rare.

PMID- 9266390
TI  - Biochemical and molecular analysis of an X-linked case of Leigh syndrome
      associated with thiamin-responsive pyruvate dehydrogenase deficiency.
AB  - We report molecular analysis of thiamin-responsive pyruvate dehydrogenase complex
      (PDHC) deficiency in a patient with an X-linked form of Leigh syndrome. PDHC
      activity in cultured lymphoblastoid cells of this patient and his asymptomatic
      mother were normal in the presence of a high thiamin pyrophosphate (TPP)
      concentration (0.4 mmol/L). However, in the presence of a low concentration (1 x
      10(-4) mmol/L) of TPP, the activity was significantly decreased, indicating that
      PDHC deficiency in this patient was due to decreased affinity of PDHC for TPP.
      The patient's older brother also was diagnosed as PDHC deficiency with Leigh
      syndrome, suggesting that PDHC deficiency in these two brothers was not a de novo
      mutation. Sequencing of the X-linked PDHC E1 alpha subunit revealed a C-->G point
      mutation at nucleotide 787, resulting in a substitution of glycine for arginine
      263. Restriction enzyme analysis of the E1 alpha gene revealed that the mother
      was a heterozygote, indicating that thiamin-responsive PDHC deficiency associated
      with Leigh syndrome due to this mutation is transmitted by X-linked inheritance.

PMID- 9266391
TI  - A longitudinal study of cognitive functioning in patients with classical
      galactosaemia, including a cohort treated with oral uridine.
AB  - Existing longitudinal data on patients with classical galactosaemia suggests that
      neurocognitive functioning is impaired and, in isolated case reports, may show a
      decline in performance over time. The present study explored whether there are
      long-term changes in cognitive abilities in patients with galactosaemia and
      whether oral uridine can improve neurocognitive performance. Thirty-five patients
      (18 males, 17 females), 29 of whom received oral uridine powder at 150 mg/kg per
      day (divided dose, three times daily), were evaluated over a 2-5-year period with
      the Woodcock-Johnson Revised Cognitive Abilities Test, three academic achievement
      tests, and the Beery Test of Visual Motor Integration. Results showed that the
      uridine cohort and a comparison group that received only dietary restriction made
      small gains in cognitive performance over the treatment period and the size of
      the gains did not differ significantly. Seven subjects who started uridine prior
      to the age of 14 months did not differ significantly in their cognitive test
      scores at an average age of 3.5 years from a group of older children who had
      begun treatment at 4.5 years of age. These results provide no support for any
      developmental or uridine-treatment-related change in cognitive functioning for
      this sample of galactosaemic subjects.

PMID- 9266392
TI  - A novel acid alpha-glucosidase mutation identified in a Pakistani family with
      glycogen storage disease type II.
AB  - A novel mutation, C118T, in exon 2 of the acid alpha-glucosidase gene has been
      found in an infant with glycogen storage disease type II. This mutation is
      predicted to result in protein truncation. The phenotype was that of the severe
      infantile form of the disorder with lack of motor development, but with eye
      regard, social smile and vocalization. The parents were heterozygous for C118T
      and belong to an Islamic community opposed to termination of pregnancy. As the
      C118T mutation results in the loss of one of two AvaI sites present in an
      informative PCR product, reliable premarriage carrier detection became possible
      and was acceptable to the members of this extended family.

PMID- 9266393
TI  - Metabolic control and renal dysfunction in type I glycogen storage disease.
AB  - This study was undertaken to determine the effect on renal function of continuous
      glucose therapy from early childhood. Twenty-three subjects, median age 13.9
      years, range 5.9-26.9 years, with type I glycogen storage disease (GSDI) treated
      with continuous glucose therapy from a median age of 1.3 years, range 0.1-12.9
      years, had 24 h monitoring of metabolites and glucoregulatory hormones on their
      home feeding regimen to assess metabolic control at approximately yearly
      intervals for a median duration of 8 years. During the most recent evaluation, 24
      h urinary albumin excretion rate (AER), kidney size, and creatinine clearance
      (Ccr) were measured. CCr was unrelated to age and was increased (> 2.33 ml/s per
      1.73 m2) in 10/23 (43%). Mean kidney length exceeded 2SD in 16/23 (70%). AER was
      normal in all five subjects < 10 years and was increased (> 10 micrograms/min) in
      8/23 (35%), all > 10 years of age. AER was significantly greater in subject of
      similar age who started continuous glucose therapy later in childhood and was
      significantly higher in subjects with lower mean 24 h plasma glucose
      concentrations and higher mean 24 h blood lactate concentrations, both at the
      time of assessment of renal function and over the preceding 5 years. GSDI
      subjects with persistently elevated concentrations of blood lactate, serum lipids
      and uric acid are at increased risk of nephropathy. Optimal dietary therapy
      instituted early in life may delay, prevent, or slow the progression of renal
      disease.

PMID- 9266394
TI  - A new case of multiple mitochondrial enzyme deficiencies with decreased amount of
      heat shock protein 60.
AB  - Heat shock protein 60 (hsp60) is a mitochondrial matrix protein involved in the
      folding and correct assembly of polypeptides into complex mitochondrial enzymes.
      Its deficiency has recently been described as the most likely primary cause of
      congenital lactic acidaemia with multiple mitochondrial enzyme deficiencies in a
      female patient. We describe a new case of a girl with a substantially decreased
      amount of hsp60 in cultured fibroblasts. She presented from birth with hypotonia,
      unusual facial features, feeding difficulties and failure to thrive. Death
      occurred at age 4.5 years. Biochemical findings included metabolic acidosis with
      lactic acidaemia, hyperammonaemia and intermittent ketosis. In contrast to the
      previously reported case, organic acid analysis showed an altered profile
      throughout her life. In agreement with this profile, various mitochondrial enzyme
      activities were deficient in cultured fibroblasts, including enzymes of the
      respiratory chain and the Krebs cycle, the pyruvate dehydrogenase complex and the
      mitochondrial biotindependent carboxylases. Fibroblast mitochondria showed
      ultrastructural abnormalities, were swollen, and were mainly localized around the
      nucleus. The description of a second case of multiple mitochondrial enzyme
      deficiencies with reduced amount of hsp60 supports the idea that hsp60 deficiency
      might be a more common cause of mitochondrial disease. This opens new
      possibilities for the diagnosis and understanding of congenital lactic acidaemia.

PMID- 9266395
TI  - Highly increased CSF concentrations of cholesterol precursors in Smith-Lemli
      Opitz syndrome.
AB  - The Smith-Lemli-Opitz syndrome is a genetic disorder characterized by typical
      clinical features including reduced myelination of both brain and peripheral
      nervous system and defective cholesterol biosynthesis. In patients this results
      in very low cholesterol concentrations and accumulation of cholesterol precursors
      in plasma, tissues, cultured cells and faeces. We now show that the cholesterol
      concentration in CSF of Smith-Lemli-Opitz patients is markedly decreased and that
      7- and 8-dehydrocholesterol concentrations are highly increased in comparison to
      controls. Moreover, dietary treatment of patients with cholesterol seems not to
      affect CSF cholesterol concentration.

PMID- 9266396
TI  - Effect of plasma alpha-tocopherol on leukotriene E4 excretion in genetic vitamin
      E deficiency.
AB  - Studying the biological effects of vitamin e in humans is difficult because
      conditions involving vitamin E deficiency are usually associated with chronic
      multiple pathology. Genetic vitamin E deficiency caused by a deficient alpha
      tocopherol transport protein offers unique possibilities for study of vitamin E
      effects since the patients can be studied in good general health. In such a
      patient we manipulated plasma alpha-tocopherol levels in a wide range by varying
      oral alpha-tocopherol supplements and measured urinary leukotriene E4 (LTE4)
      concentrations. LTE4 excretion proved inversely correlated to plasma alpha
      tocopherol levels. This strongly suggests that in genetic vitamin E deficiency,
      alpha-tocopherol influences formation of leukotrienes in vivo.

PMID- 9266398
TI  - Plasma chitotriosidase activity in Gaucher disease patients who have been treated
      either by bone marrow transplantation or by enzyme replacement therapy with
      alglucerase.
AB  - A marked elevation in plasma chitotriosidase (chitinase) activity has recently
      been observed in patients with Gaucher disease (Hollak et al 1994). It has been
      suggested that this phenomenon may serve as a useful marker for the efficacy of
      treatment with enzyme replacement therapy. We report our findings on the
      comparison of plasma chitotriosidase levels in 8 patients treated with the
      modified human placental enzyme alglucerase and 8 patients treated by allogeneic
      bone marrow transplantation (BMT). Two years after transplantation the activity
      in the BMT patients had fallen by over 93% and has continued to fall. Now, 5-12
      years post-BMT, 6 patients have normal levels of plasma chitotriosidase and 2
      patients have activities slightly above the reference range. Patients have been
      treated with alglucerase for a considerably shorter time than the BMT patients.
      The chitotriosidase activities have fallen and are continuing to fall in 7
      patients but at a slower rate than in the BMT group. In one patient there has
      been no appreciable change in activity over the last 6 months, which would
      suggest that she may be on too low a dosage.

PMID- 9266397
TI  - Prevalent mutations in the GALC gene of patients with Krabbe disease of Dutch and
      other European origin.
AB  - Sixty-four unrelated patients with infantile Krabbe disease (globoid cell
      leukodystrophy, GLD) of Dutch (n = 41) or other European origin (n = 23) were
      screened for the presence of a large 30 kb deletion starting in intron 10
      (IVS10del30 kb), a base substitution 1538T(T513M) and a polymorphism, 502T. The
      deletion and the T513M mutation were present in 52% and 8.5%, respectively, of
      the 82 GALC alleles of the Dutch patients. The 502T polymorphism, which had an
      allele frequency of 5.3% in a Dutch control panel, occurred in 65% of the GLD
      alleles. Analysis of patients and both parents in 26 of the families showed that
      del30 kb was invariably associated with 502T. However, 502T was also present on
      40% of the GLD alleles with an as yet unidentified mutation, which is 7.5 times
      higher than its frequency in controls. This suggests that besides del30 kb at
      least one other relatively frequent mutation has arisen on the 502T GALC allele.
      A relatively high incidence of del30 kb was also found in 23 other European (non
      Dutch) patients (allele frequency 35%), but T513M did not occur in this group.
      Practical examples described in this report illustrate the potential usefulness
      of mutation analysis in many families with Krabbe disease for heterozygote
      detection and prenatal diagnosis.

PMID- 9266399
TI  - Vitamin B12 deficiency in an adult phenylketonuric patient.

PMID- 9266400
TI  - Renal tubular dysfunction in multiple acyl-CoA dehydrogenase deficiency.

PMID- 9266401
TI  - Adenylosuccinase deficiency presenting with epilepsy in early infancy.

PMID- 9266402
TI  - Fanconi-Bickel syndrome presenting in neonatal screening for galactosaemia.

PMID- 9266403
TI  - Glycerol kinase deficiency and adrenal hypoplasia congenita.

PMID- 9266404
TI  - Recessive congenital methaemoglobinaemia type II a new mutation which causes
      incorrect splicing in the NADH-cytochrome b5 reductase gene.

PMID- 9266405
TI  - Incorrect assignment of N370S mutation status by mismatched PCR/RFLP method in
      two Gaucher patients.

PMID- 9266406
TI  - Symptomatic hyperinsulinism reversed by dietary manipulation in glycogenosis type
      III.

PMID- 9266407
TI  - Fenugreek odour in maple syrup urine disease.

PMID- 9266408
TI  - Two novel mutations in patients with atypical phenotypes of acid sphingomyelinase
      deficiency.

PMID- 9266409
TI  - Treatment strategies for neurodegenerative diseases based on trophic factors and
      cell transplantation techniques.
AB  - Treatment strategies based on transfer of genes, molecules, or cells to the
      central nervous system are summarized. When neurons are already degenerated,
      functional compensation can be effected by grafts of syngeneic or allogenic
      tissue to the target area. This technique is undergoing clinical trials in
      Parkinson's disease. Before degeneration has occurred, it may be possible to
      rescue "stressed" neurons, and stimulate terminal outgrowth using treatment with
      neurotrophic factors. Such approaches, with an emphasis on the NGF family of
      neurotrophins and their receptors, are reviewed. Finally, new molecular biology
      techniques may permit the transfer of genes directly into non-dividing cells of
      the central nervous system. These three approaches may have a more general
      applicability, and become important not only in neurodegenerative diseases, but
      also in other afflictions of the nervous system such as ischemia, stroke and
      injury.

PMID- 9266410
TI  - Models of Alzheimer's disease: cellular and molecular aspects.
AB  - Glucose metabolism in the brain is an important process that influences many
      normal cellular processes, from neurotransmitter synthesis to ATP production.
      While cortisol and insulin have opposing effects on glucose metabolism,
      desensitization of the neuronal insulin receptor results in metabolic
      abnormalities. In the normal aging brain, glucose/energy metabolism is decreased
      slightly. In the majority of cases. Alzheimer's disease is sporadic and has a
      late onset. Therefore, age-related variations in cellular metabolism following
      the principle of self-organized criticality may come into focus with respect to
      the etiopathogenesis of this neurodegenerative disorder. As a possible primary
      abnormal event in late-onset sporadic DAT, a prolonged desensitization of the
      neuronal insulin receptor is assumed to be responsible for cascade-like
      abnormalities in oxidative energy metabolism and related metabolism with impacts
      on amyloid formation.

PMID- 9266411
TI  - The relationship of Alzheimer-type pathology to dementia in Parkinson's disease.
AB  - Lewy body degeneration of the subcortical nuclei other than the substantia nigra
      is common in PD and may represent the substrate for a higher vulnerability to
      dementia in patients with PD. Cortical pathologies of Alzheimer and Lewy body
      type seem to be the major determinants of dementia. The prevalence of Alzheimer's
      disease is not increased in PD, but "early" cortical Alzheimer lesions (usually
      sub-clinical in normal controls) are frequently associated with dementia in PD.
      Furthermore, dementia in PD is heterogeneous and should always prompt the
      clinician to search for treatable causes.

PMID- 9266412
TI  - Models to study the role of neurotrophic factors in neurodegeneration.
AB  - The physiological functions of neurotrophic factors, such as nerve growth factor
      (NGF), in supporting the survival and differentiation of specific neurons during
      early development has in many cases been well established. Recent studies have
      shown that neurotrophic factors can also protect vulnerable neurons against a
      variety of mechanical and chemical injuries. The role and the effects of
      neurotrophic factors in various neurological diseases are however less known.
      Neurodegenerative diseases such as Parkinson and Alzheimer's diseases as well as
      amyotrophic lateral sclerosis (ALS) are characterized by an impaired function and
      ultimate loss of specific populations of neurons. The study of the ethiology and
      molecular biology of these diseases has for a long time been hampered by the lack
      of good animal models mimicked part of the human disease in experimental animals.
      Here we will discuss some of the current approaches taken in these studies as
      well as address the important question of the possible beneficial effect of
      neurotrophic factors in alleviating the symptoms and possibly retarding the
      course of neurodegenerative diseases.

PMID- 9266414
TI  - Immunological aspects of experimental allergic encephalomyelitis and multiple
      sclerosis and their application for new therapeutic strategies.
AB  - The etiology of multiple sclerosis (MS), a demyelinating disorder of the central
      nervous system (CNS), is not yet known. Immunological, clinical and pathological
      studies suggest, however, that T lymphocytes directed against myelin antigens are
      involved in the pathogenesis of MS. The examination of an experimental animal
      model for MS, experimental allergic encephalomyelitis (EAE), demonstrated that
      myelin basic protein-(MBP) or proteolipidprotein-(PLP) specific T cells mediate
      the destruction of CNS myelin. In recent years, elegant studies in EAE showed
      that encephalitogenic T cells recognize short peptides of MBP or PLP in the
      context of MHC/HLA-class II molecules, express a restricted number of T cell
      receptor (TCR) molecules and secrete interferon-gamma and tumor necrosis factor
      alpha/beta. Understanding the pathogenetic steps of demyelination at the
      molecular level led to highly specific immunotherapies of EAE targeting each
      individual molecule. MBP- and PLP-specific T cells with similar properties could
      also be isolated from MS patients and control individuals. Due to their
      heterogeneity in terms of specificity, function and TCR usage, it was difficult,
      however, to draw definite conclusions from these results, so far. The recent
      approval of interferon-beta, a cytokine that antagonizes a number of the effects
      of interferon-gamma, for the treatment of MS has raised great interest in
      examining novel strategies for immunotherapies in MS. The basic concepts as well
      as the current candidates for such new immunotherapies will be outlined in this
      brief article.

PMID- 9266413
TI  - Induction of experimental autoimmune encephalomyelitis by CD4+ T cells specific
      for an astrocyte protein, S100 beta.
AB  - S100 beta protein is a calcium binding protein that is not only expressed by
      astrocytes in the CNS, but also in many other tissues including the eye, thymus,
      spleen and lymph nodes. Despite this tissue distribution, which was expected to
      induce a firm state of self-tolerance to S100 beta, the Lewis rat mounts a strong
      T cell response to this autoantigen. The pathogenicity of this T cell response
      was demonstrated by the adoptive transfer of S100 beta-specific T cells which
      induced an inflammatory response in the CNS and eye of naive syngeneic
      recipients. The distribution of lesions in this novel model of EAE resembles that
      seen in some patients with MS, suggesting that the initial autoimmune insult in
      MS may be directed against a non-myelin antigen co-expressed in the CNS and extra
      neural tissues.

PMID- 9266415
TI  - Nigrostriatal neuronal death in Parkinson's disease--a passive or an active
      genetically-controlled process?
AB  - The cause for the rather selective degeneration of the nigrostriatal dopaminergic
      (DA) neurons in Parkinson's disease (PD) is still enigmatic. The major current
      hypothesis suggests that nigral neuronal death in PD is due to excessive oxidant
      stress generated by auto- and enzymatic oxidation of DA, formation of
      neuromelanin and presence of high concentrations of iron. Such cell death is
      generally regarded as a passive, necrotic process, mainly resulting from membrane
      lipid peroxidation, leading to its dysfunction and rupture and then to neuronal
      disintegration. We suggest a novel approach, that views neuronal degeneration in
      PD as an active process that occurs mainly the nuclear level. Our concept is
      based on the following observations: (1) Nigral histopathology in PD is
      characterized by a slow, protracted degeneration of individual neurons. We
      propose that it may be due to apoptosis [programmed cell-death (PCD), an active,
      genetically-controlled, intrinsic program of cell "suicide"] rather than to
      necrotic cell death. (2) DA exerts antitumor effect on melanoma and neuroblastoma
      cells. (3) Many anticancer drugs, trigger PCD by causing DNA damage. (4) DA has
      been shown to be genotoxic. (5) We recently first showed that DA, the endogenous
      neurotransmitter in the nigra, can trigger apoptosis in cultured, postmitotic
      sympathetic neurons. (6) We have also shown that PC-12 cells, transfected with
      the bcl-2 gene (a proto-oncogene that inhibits PCD) are relatively resistant to
      DA-apoptotic effect. Degeneration of nigrostriatal neurons in PD may therefore be
      linked to dysregulation of the control mechanisms that normally restrain the PCD
      triggering-potential of their own neurotransmitter.

PMID- 9266416
TI  - Animal model and in vitro studies of anti neurofilament antibodies mediated
      neurodegeneration in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is associated with serum antibodies directed
      specifically against phosphorylated epitopes highly enriched in the heavy
      neurofilament protein NF-H of cholinergic neurons. Prolonged immunization of rats
      with these molecules but not with other NF-H isoforms results in cognitive
      impairments. This animal model, termed experimental autoimmune dementia (EAD),
      supports a role for such antibodies in neurodegeneration in AD. In the present
      study we investigated the cellular and immunological mechanisms underlying the
      cognitive defects in EAD. Immunohistochemical studies revealed that IgG
      accumulate in the septum, hippocampus and in the entorhinal cortex of the EAD
      rats. This is accompanied by a marked reduction in the density of septal
      cholinergic neurons. An inverse correlation was observed between the level of IgG
      in the septum of individual EAD rats and the density of their septal cholinergic
      neurons. Time course studies revealed that the decrease in the density of
      cholinergic neurons in the septum of EAD rats and the accumulation of IgG in this
      brain area have the same time course and are both significant by three to four
      months following the initiation of immunization with cholinergic NF-H. The
      cognitive deficits of the EAD rats evolve more slowly and are pronounced only
      after six months following the initation of immunization. In vitro studies
      revealed that anti NF-H IgG bind to the outer surface of neurons in tissue
      cultures of rat forebrain and can affect neuronal viability. These AD and in
      vitro findings provide model systems for studying the mechanisms underlying the
      neuropathological effects of specific anti NF-H antibodies.

PMID- 9266417
TI  - Cop 1 as a candidate drug for multiple sclerosis.
AB  - Copolymer 1 (Cop 1), a synthetic copolymer of amino acids, is very effective in
      suppression of experimental autoimmune encephalomyelitis (EAE), the animal model
      for multiple sclerosis (MS). Cop 1 was found incapable of inducing EAE, yet it
      suppressed EAE in a variety of animal species, including primates. The
      immunological cross-reaction between the myelin basic protein (MBP) and Cop 1
      serves as the basis for the suppressive activity of Cop 1 in EAE, by the
      induction of antigen-specific suppressor cells and competition with MBP for
      binding to major histocompatibility complex (MHC) molecules. Clinical trials with
      Cop 1, both Phase II and Phase III, were performed in relapsing-remitting (E-R)
      patients. The latter, a two-year multicenter double blind trial with 251
      participating patients was conducted at 11 leading medical centers in the USA. It
      demonstrated a significant beneficial effect of Cop 1 in both diminishing the
      rate of exacerbations and improving the clinical status. The side effects of Cop
      1 were only minimal. The cumulative results indicate that Cop 1 is a promising
      candidate drug for multiple sclerosis.

PMID- 9266418
TI  - Possible role of the cholinergic system and disease models.
AB  - Memory impairment associated with the loss of cortical cholinergic neurons in AD
      has stimulated the development of animal models based on blockade or destruction
      of these systems. Strategies include mechanical lesions, local injection of
      excitotoxic amino acids or ethylcholine aziridinium (AF 64A), which disrupt
      reference and working memory in rats, but lack specificity for cholinergic
      systems. Other models involving, reduction in cerebral blood flow and
      interference with oxidative metabolism of glucose, mimic those found in AD, and
      also interfere with working and long-term memory in the rat. Memory impairments
      can be reversed by acetylcholinesterase inhibitors and cholinergic agonists but
      beneficial effects of these agents in AD patients are small and inconsistent.
      This may be partly due to unfavorable pharmacokinetics and dose-limiting side
      effects of existing drugs. Newer, brain specific acetylcholinesterase inhibitors
      and M1 muscarinic agonists with a lower incidence of unwanted effects are
      currently being evaluated.

PMID- 9266420
TI  - Role of interferons in demyelinating disease.
AB  - Interferon beta 1b (Betaseron) was licensed by the U.S. Federal Food and Drug
      Administration in July 1993 as the first treatment to alter the natural history
      of multiple sclerosis (MS). The drug, injected subcutaneously every other day,
      reduced the frequency of relapses and the expansion of central white matter
      pathology as measured by MRI. Twelve previous interferon trials in MS, employing
      a variety of interferon preparations, doses and routes of administration,
      preceded this trial and provided the scientific foundation for its success. Beta
      interferon therapy probably inhibits gamma interferon to achieve its therapeutic
      effect. Future MS therapy may require combination treatment with multiple agents
      with complimentary immunologic effects.

PMID- 9266419
TI  - Loss of dopaminergic neurons in parkinsonism: possible role of reactive dopamine
      metabolites.
AB  - Parkinson's disease affects one out of every 100 people above the age of 55. Its
      cause is unknown and although the symptoms can be treated, there is no cure. The
      disease is associated with the selective loss of neurons that contain biogenic
      amines, and among these it is the dopamine (DA) neurons of the nigrostraital
      projection that are the most consistently and severely affected (Bernheimer et
      al., 1973). In this review we discuss the possibility that DA may act as an
      endogenous neurotoxin, causing the degeneration of the very neurons that release
      it. We further suggest that although treatments which increase the synthesis and
      release of DA reduce the symptoms, they also may serve to exacerbate the
      neurodegenerative process. We propose that the treatments which increase the
      antioxidant capacity of brain may be protective.

PMID- 9266421
TI  - Role of interferons in demyelinating diseases.
AB  - IFN beta-1b reduces the frequency of major multiple sclerosis attacks by 50
      percent. Serial MRI scanning over the course of the clinical trial that led to
      approval of the agent revealed a significant lessening both in disease activity
      and in accumulating burden of disease in IFN beta-1b-treated patients compared to
      placebo-treated controls. The mechanism by which IFN beta-1b exerts its
      beneficial effect in multiple sclerosis is unknown. T suppressor cell function
      fails during MS attacks and is persistently subnormal in multiple sclerosis
      patients with progressive disease. IFN beta-1b partially restores suppressor
      function in multiple sclerosis patients. IFN beta-1b also inhibits release of
      lymphotoxin, tumor necrosis factor, and interferon gamma, at least in vitro. All
      three cytokines are toxic to oligodendrocytes. In contrast; production of
      transforming growth factor beta-1 (TGF beta 1) is increased by IFN beta-1b. TGF
      beta 1 is an immunosuppressive cytokine. All of the above listed actions of IFN
      beta-1b could contribute to its beneficial effect. Perhaps all do.

PMID- 9266422
TI  - Mechanism of amyloid beta protein induced neuronal cell death: current concepts
      and future perspectives.
AB  - Amyloid beta protein (A beta) is a 40 to 43 amino acid peptide which is
      associated with plaques in the brains of Alzheimer's patients and is cytotoxic to
      cultured neurons. A number of antioxidants protect both primary central nervous
      system (CNS) cultures and clonal cell lines from A beta toxicity, suggesting that
      one pathway to A beta cytotoxicity results in free radical damage. A beta causes
      increased levels of H2O2 and lipid peroxides to accumulate in cells. The H2O2
      degrading enzyme catalase protects cells from A beta toxicity. Clonal cell lines
      selected for their resistance to A beta toxicity also become resistant to the
      cytolytic action of H2O2. In addition, A beta induces NF-kB activity, a
      transcription factor thought to be regulated by oxidative stress. Finally, A beta
      induced H2O2 production and A beta toxicity are blocked by reagents which inhibit
      flavin oxidases, suggesting that A beta activates a member of this class of
      enzymes. These results show that the cytotoxic action of A beta on neurons
      results from free radical damage to susceptible cells (Behl et al., 1994b).

PMID- 9266423
TI  - From prion diseases to Alzheimer's disease.
AB  - Recent advances in the transgenetics of prion diseases and Alzheimer's disease
      have led to a clearer understanding of the relationship between these two
      diseases and the pathogenic mechanisms underlying the two disorders. Earlier
      studies of transgenic mice expressing prion protein (PrP) underscored the
      importance of PrP levels and PrP primary structure on the resultant phenotype.
      Three major parameters influencing the phenotypes of mice expressing the
      Alzheimer amyloid precursor protein (APP) have also been identified: 1) APP
      levels; 2) APP primary structure; and 3) mouse host strain. The effects and
      implications of these parameters in transgenic mice expressing APP are discussed.

PMID- 9266424
TI  - A phosphorylation cascade in the basal ganglia of the mammalian brain: regulation
      by the D-1 dopamine receptor. A mathematical model of known biochemical
      reactions.
AB  - Stimulation of the dopamine D-1 receptor in the corpus striatum initiates a
      cascade of biochemical events. These events include: activation of adenylate
      cyclase, stimulation of cAMP-dependent protein kinase, protein phosphorylation
      and inhibition of phosphoprotein phosphotase-1. This article presents and
      discusses a mathematical model of these biochemical events (and their dependence
      upon the concentration of cytosolic calcium). According to this model, the
      activity of calcineurin (which is regulated by the concentration of cytosolic
      calcium ions) counterbalances the activity of the "D-1 cascade". The combined
      activity of the "D-1 cascade" and calcineurin can regulate the activity of
      calcium- and calmodulin-dependent protein kinase II.

PMID- 9266425
TI  - Molecular heterogeneity of neurotransporters: implications for neurodegeneration.
AB  - Neurotransporters are high-affinity transport proteins located in the plasma
      membrane of both presynaptic nerve and glial cells that mediate the removal of
      neurotransmitters from the synaptic cleft or represent intracellular transport
      systems that concentrate neurotransmitters in synaptic vesicles. They comprise
      three subgroups, Na+/Cl(-)- or Na+/K(+)-dependent cell surface transporters and
      H(+)-dependent transporters associated with synaptic vesicles. The new insights
      into neurotransporter diversity provide the means for novel approaches of
      studying neurotransmitter uptake processes at the molecular level, such as
      substrate translocation and antagonist binding as well as regulation of gene
      expression, of intracellular trafficking, and of posttranslational modification.
      Moreover, modeling neurotransporter-related disorders and therapeutic strategies
      in genetically engineered animals are now feasible research strategies. Through
      an improved understanding of the modulation of neurotransporter function in the
      brain, it may be possible to identify the molecular factors underlying the
      etiopathogenesis and pathophysiology of neurodegenerative disorders. Due to their
      specificity for distinct neuronal systems, neurotransporters and their genes are
      potential targets for novel therapeutic strategies.

PMID- 9266426
TI  - Central nervous system cytokines and their relevance for neurotoxicity and
      apoptosis.
AB  - Cytokines are molecules that are synthesized not only by the immune system, but
      also by cells in the central nervous system, including neurons, glia, and brain
      vascular cells. In the brain, cytokines can be neuroprotective or they can
      contribute to neurodegeneration. The role of cytokines in the regulation of
      normal and abnormal brain function represents a rapidly growing frontier in
      neuroscience. Cytokines are pleiotropic and redundant, and they can modulate the
      effects of neurotransmitters and neuropeptides; thus, in order to understand the
      effects of brain cytokines on apoptosis and toxicity, it is necessary to study
      the temporal and spatial expression of complex networks of cytokines, growth
      factors, neuropeptides, and neurotransmitters. This effort is currently in
      progress in many centers. Modulation of cytokine function in the central nervous
      system represents a new therapeutic strategy for neurodegeneration.

PMID- 9266427
TI  - Genetics of multiple sclerosis--how could disease-associated HLA-types contribute
      to pathogenesis?
AB  - Multiple sclerosis is a chronic demyelinating disease of the central nervous
      system in young adults. It is considered a T cell-mediated autoimmune disease
      which is probably triggered by exogenous events, e.g. infectious agents, in
      susceptible individuals. Population, family and twin studies indicate that
      genetic factors and most likely several genes are associated with disease, but it
      is clear from the concordance rates of identical twins (25-30%) that genetic
      background as well as exogenous or somatic events are required to develop
      disease. Among many candidate genes which have been analyzed during recent years,
      the strongest association was shown for genes of the HLA-class II complex, in
      particular HLA-DR15 Dw2 and -DQw6. At present, it is not clear how the expression
      of a particular HLA-class II gene translates into susceptibility to develop an
      organ-specific autoimmune disease. Potential explanations how this could occur
      will be discussed.

PMID- 9266428
TI  - Modulation of control mechanisms of dopamine-induced apoptosis--a future approach
      to the treatment of Parkinson's disease?
AB  - The cause for the progressive and selective degeneration of the dopaminergic (DA)
      nigrostriatal neurons in Parkinson's disease (PD) is still unknown. We suggest a
      novel approach, that links this neuronal degenerative process to inappropriate
      triggering of apoptosis, an active, controlled program of cellular self
      destruction, by excess oxidative stress mediated by DA metabolism. In support of
      this concept, we found that DA, the endogenous neurotransmitter, is capable of
      initiating apoptosis in cultured, postmitotic chick sympathetic neurons, an
      observation further extended to other cellular systems (PC-12 cells, cerebellar
      granular cells, thymocytes, splenocytes). In comparing the relative apoptosis
      triggering potency of other mononamine neurotransmitters, DA was found to be the
      most active, whereas norepinephrine and serotonin had a moderate and a mild
      effects, respectively. This grading can be correlated with the relative
      involvement of the relevant neuronal systems (i.e., substantia nigra, locus
      ceruleus and raphe nuclei) in PD. We therefore hypothesize that neuronal
      degeneration in PD may be caused, at least in part, by a failure, either
      inherited or acquired, in cellular control systems of apoptosis, that may
      normally restrain the lethal potential of these endogenous neuro-transmitters and
      their potentially-toxic oxidation products. We therefore point at apoptosis
      control systems as a critical scene of events, where the fate of nigrostriatal
      neurons is ultimately determined, and whose modulation may yield attenuation of
      the neuronal degenerative process. In support of this concept, we found that
      vector-driven stable expression of the proto-oncogene bcl-2, an inhibitor of
      apoptosis, can exert powerful cellular protection against DA toxicity in rat
      pheochromocytoma PC-12 cells. Furthermore, cell extracts from bcl-2-expressing
      cells were found to markedly inhibit in vitro oxidation of DA and production of
      DA-melanin. We also found that expression of bcl-2 can inhibit the decrease in
      intracellular reduced thiol (-SH) groups which we observed following exposure to
      DA. Research of the bcl-2 system and associated control mechanisms of apoptosis,
      possibly acting in association with intra-cellular anti-oxidant pathways, may
      therefore lead to novel therapeutic approaches for neuroprotection in PD.

PMID- 9266429
TI  - GTP cyclohydrolase I gene, dystonia, juvenile parkinsonism, and Parkinson's
      disease.
AB  - GTP cyclohydrolase I is the rate-limiting enzyme for the biosynthesis of
      tetrahydrobiopterin, which is the cofactor for tyrosine hydroxylase, the rate
      limiting enzyme for dopamine biosynthesis. We found that dominantly inherited,
      hereditary progressive dystonia (HPD), first described by Segawa and also called
      dopa responsive dystonia (DRD), is caused by the mutations of GTP cyclohydrolase
      I gene, the partial decrease in the enzyme activity, and probably in striatal
      dopamine level, to less than 20% of the normal values. Juvenile parkinsonism and
      Parkinson's disease are also striatal dopamine deficiency, but no mutation in the
      enzyme has not been found, and they are supposed to be different from HPD/DRD in
      which no cell death of the nigrostriatal dopamine neurons occurs.

PMID- 9266430
TI  - MRI as a method to reveal in-vivo pathology in MS.
AB  - Multiple sclerosis is primarily a disease of myelin. The degeneration of neurons
      and axons in MS has not been considered to be a major factor until recently.
      Magnetic resonance (MR) techniques have helped a great deal in describing the
      evolution of MS lesions over time. Some pathological and MR studies have shown
      that in the chronic stage of MS, axonal loss occurs. Further studies using MR
      techniques should help to understand this phenomenon as it occurs in vivo.

PMID- 9266431
TI  - Familial amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis is sporadic in ninety percent of cases and familial
      (FALS) in ten percent. Both forms of FALS whether transmitted as an autosomal
      dominant (DFALS) or as an autosomal recessive (RFALS) trait is genetically
      heterogeneous. The locus for one form of RFALS maps to chromosome 2q33. Fifteen
      percent of DFALS families have mutations in the gene for Cu, Zn superoxide
      dismutase (SOD1) gene which is coded on chromosome 21. These mutations result in
      decreased SOD1 activity and shortened half-life of the protein in most instances.
      Transgenic mice overexpressing mutated SOD1 protein develop an ALS-like disease
      which suggests that the degeneration of motor neurons in DFALS is caused by the
      gain of a novel toxic function by mutated SOD1 rather than by the decrease of
      SOD1 activity. Possible mechanisms of the novel neurotoxic function of mutated
      SOD1 are discussed.

PMID- 9266432
TI  - Chronic administration of a partial agonist at strychnine-insensitive glycine
      receptors: a novel experimental approach to the treatment of ischemias.
AB  - During the past decade, converging lines of evidence have linked the abnormal
      release or leak of excitatory amino acids to the neurodegeneration associated
      with a wide range of pathologies including cerebral ischemias, Huntington's
      disease, and AIDS dementia (Coyle and Robinson, 1987; Lipton, 1994; Meldrum,
      1994). Pharmacological studies indicate that activation of both ionotropic and
      metabotropic glutamate receptors can substantially contribute to excitotoxic cell
      damage (Choi, 1992; Pizzi et al., 1993; Sheardown et al., 1993; Xue et al.,
      1994). Based on these findings, therapeutic strategies based on blunting or
      blocking glutamatergic transmission may be useful in treating a variety of
      neurodegenerative disorders.

PMID- 9266433
TI  - Apoptosis in neurodegenerative disorders: potential for therapy by modifying gene
      transcription.
AB  - Apoptotic, rather than necrotic, nerve cell death now appears as likely to
      underlie a number of common neurological conditions including stroke, Alzheimer's
      disease, Parkinson's disease, hereditary retinal dystrophies and Amyotrophic
      Lateral Sclerosis. Apoptotic neuronal death is a delayed, multistep process and
      therefore offers a therapeutic opportunity if one or more of these steps can be
      interrupted or reversed. Research is beginning to show how specific
      macromolecules play a role in determining the apoptotic death process. We are
      particularly interested in the critical nature of gradual mitochondrial failure
      in the apoptotic process and propose that a maintenance of mitochondrial function
      through the pharmacological modulation of gene expression offers an opportunity
      for the effective treatment of some types of neurological dysfunction. Our
      research into the development of small diffusible molecules that reduce apoptosis
      has grown from studies of the irreversible MAO-B inhibitor (-)-deprenyl. (-)
      Deprenyl can reduce neuronal death independently of MAO-B inhibition even after
      neurons have sustained seemingly lethal damage. (-)-Deprenyl can also influence
      the process outgrowth of some glial and neuronal populations and can reduce the
      concentrations of oxidative radicals in damaged cells at concentrations too small
      to inhibit MAO. In accord with earlier work of others, we showed that (-)
      deprenyl alters the expression of a number of mRNAs or of proteins in nerve and
      glial cells and that the alterations in gene expression/protein synthesis are the
      result of a selective action on transcription. The alterations in gene
      expression/protein synthesis are accompanied by a decrease in DNA fragmentation
      characteristic of apoptosis and the death of responsive cells. The onco-proteins
      Bcl-2 and Bax and the scavenger proteins Cu/Zn superoxide dismutase (SOD1) and Mn
      superoxide dismutase (SOD-2) are among the 40-50 proteins whose synthesis is
      altered by (-)-deprenyl. Since mitochondrial membrane potential correlates with
      mitochondrial ATP production, we have used confocal laser imaging techniques in
      living cells to show that the transcriptional changes induced by (-)-deprenyl
      result in a maintenance of mitochondrial membrane potential, a decrease in
      intramitochondrial calcium and a decrease in cytoplasmic oxidative radical
      levels. We therefore propose that (-)-deprenyl acts on gene expression to
      maintain mitochondrial function and decrease cytoplasmic oxidative radical levels
      and thereby reduces apoptosis. An understanding of the molecular steps by which (
      )-deprenyl selectively alters transcription may lead to the development of new
      therapies for neurodegenerative diseases.

PMID- 9266434
TI  - Disinhibition-dementia-parkinsonism-amyotrophy complex (DDPAC) is a non
      Alzheimer's frontotemporal dementia.
AB  - DDPAC was defined based on the cardinal symptoms of the syndrome found in family
      Mo. Investigation of DDPAC cases in family Mo shows non-specific pathological
      changes in a distribution that is consistent with the cardinal features of the
      disease. Genetic analysis identified a locus on chromosome 17q21-22 that produces
      this syndrome which is inherited as an autosomal dominant trait. DDPAC overlaps
      clinically and pathologically with a variety of named neurodegenerative syndromes
      and falls within the spectrum called frontotemporal dementia. The localization of
      the disease locus for DDPAC allows the testing of whether other familial
      neurodegenerative conditions also map to the same chromosomal regions. It seems
      possible that ultimately these conditions that have thus far been difficult to
      categorize will be subject to a nosology based on genetic etiology.

PMID- 9266435
TI  - Nucleolar organizing regions in primary intracranial malignant lymphomas.
AB  - Twenty-two non-immunocompromised patients with primary intracranial malignant
      lymphomas were examined on surgical material by using an argyrophilic method for
      the demonstration of nucleolar organizer regions as Ag-NORs. The
      histopathological classifications of 22 patients included 3 small lymphocytic, 7
      small cleaved, 9 large cell. 1 mixed large and small, and 2 small non-cleaved
      type. The numbers of Ag-NOR of malignant lymphoma patients varied from 1.36 to
      5.02 (mean 3.46 +/- 0.25). The mean Ag-NOR numbers in the histopathological
      subtypes were small lymphocytic 1.63, small cleaved 3.18, large 4.21, mixed large
      and small 3.47, and small non-cleaved 3.78. The number of Ag-NORs in small
      lymphocytic type was significantly less than small cleaved or large cell type (p
      < 0.05). The small cleaved type also had a smaller Ag-NOR number than the large
      cell type (p < 0.05). Except for two patients who had postoperative
      deterioration, 20 patients received postoperative irradiation ranging from 36 to
      54 Gy (median, 46 Gy). Sixteen patients had complete response to radiotherapy,
      and 4 had good partial response. Ten patients had tumor recurrence within the
      remission period of 3 months to 7 years and 10 months (median 4.8 months). Three
      patients with intracranial relapse at a remote site had a significantly longer
      remission period (mean 57.3 months) than 7 with local relapse (mean 6.29 months),
      p < 0.05. The mean Ag-NOR number of the short and long remission period were 3.13
      +/- 0.34 and 3.8 +/- 0.80, respectively. No significant difference was found
      between these two groups. The survival period was 3.2 months to 12 years (median
      20 months). The Ag-NOR numbers of survival period less than or more than 20
      months were 3.62 +/- 0.40 and 3.27 +/- 0.37, respectively. The Ag-NOR numbers did
      not correlate with either the remission or the survival period. These results
      indicate that Ag-NOR numbers may correlate with the histopathologic types, but
      not with the prognosis of primary intracranial malignant lymphomas.

PMID- 9266436
TI  - Augmentation of anti-Fas antibody-mediated apoptosis on human glioma cells by
      liposomes associated with the antibody.
AB  - We investigated the susceptibility of five human glioma cell lines to anti-Fas
      antibody. All human glioma cells tested constitutively expressed Fas antigen on
      their surfaces and the level of the expression varied slightly in each cell line.
      The cells had a low susceptibility to anti-Fas antibody-mediated apoptosis. There
      were four moderately resistant cell lines (U251-SP, U251-MG, SK-MG-1, T98) and
      one highly resistant cell line (U251 nu/nu). For this study we prepared liposomes
      containing anti-Fas antibody and studied the augmentation of the antibody
      mediated apoptosis. The liposomes induced apoptosis significantly more often than
      did anti-Fas antibody alone. These results indicate that anti-Fas antibody
      mediated apoptosis does not require a critical level of cell surface expression
      of Fas antigen but rather depends on the intensity of Fas signal transduction.

PMID- 9266437
TI  - Prognostic factors in malignant glioma: influence of the overexpression of
      oncogene and tumor-suppressor gene products on survival.
AB  - Despite the use of multimodal therapy, higher-grade glioma is still uniformly
      fatal in the adult population. There is a considerable difference between the
      length of survival in each given patient, even within the same tumor type and
      malignancy grade group, suggesting that there are factors that might
      differentially influence outcome. To identify such factors, 107 patients with
      anaplastic or malignant glioma were retrospectively investigated. Clinical
      parameters and paraclinical data on the p53, mdm2, and EGFR genes at the DNA or
      protein level were evaluated by univariate analysis and Cox proportional hazards
      regression modeling. Kaplan-Meier survival estimation demonstrated that
      immunohistochemical positivity for mdm2 protein in patients with anaplastic
      astrocytoma or with glioblastoma multiforme was associated with a shorter
      survival time (p = 0.02). P53 gene mutations and immunopositivity for the
      epidermal growth factor receptor (EGFR) protein were not significantly related to
      poor prognosis. The Cox proportional hazards model revealed immunohistochemical
      positivity for p53, mdm2, or for both of them, the presence of postoperative
      irradiation, and the extent of surgical resection of tumor to be variables
      significantly associated with prolonged survival. EGFR overexpression, age over
      60 years, and Karnofsky performance score below 40 points did not significantly
      shorten survival time. In conclusion, the present study identified
      immunohistochemically detected mdm2-protein overexpression as a statistically
      significant negative prognostic parameter in patients bearing anaplastic or
      malignant glioma. Association analysis of variables revealed a possible
      correlation between mdm2 and p53, which is also consistent with the biological
      interaction mode of both proteins in vivo.

PMID- 9266438
TI  - Immunohistochemical detection of human natural killer cell like immunoreactivity
      in human pituitary adenomas, using monoclonal antibody NK-1.
AB  - Natural killer (NK) cells are specialized lymphocytes which are characterized as
      non-T and non-B cells, as they lack classic T and B cell surface markers.
      Recently, NK like immunoreactivity has been identified in endocrine and neuronal
      tissues as well as in the tumors derived from the neuroectoderm and
      neuroendocrine system. We examined the expression of NK-1 like immunoreactivity
      in 6 normal pituitary glands and in 55 cases of neoplastic pituitaries (16 growth
      hormone (GH) producing adenomas, 14 prolactin (PRL) producing adenomas, 4
      thyrotropin (TSH) producing adenomas, 5 adrenocortocitropin (ACTH) producing
      adenomas and 16 non-functioning adenomas) immunohistochemically. The expression
      of the S-100 protein, which is a marker for folliclo-stellate (FS) cells, which
      have been reported to secrete cytokines as immuno-endocrine modulators, were also
      examined. In normal pituitary glands, NK-1 was detected in all 6 tissues in the
      cytoplasm of about 5-10% of the anterior pituitary cells. By serial sectioning
      and double immunostaining, NK-1 immunopositivity was frequently found to be
      localized in ACTH cells. The colocalization with other anterior pituitary
      hormones such as GH. PRL, the beta-subunit of luteinizing hormone (LH beta),
      follicle stimulating hormone (FSH beta). TSH beta and alpha-subunit of
      glycoprotein (alpha SU) was not observed. The S-100 immunopositive FS cells,
      which were scattered among hormone producing cells, were closely associated with
      NK-1 immunoreactive cells in the normal pituitaries. Among the 55 cases of
      pituitary adenomas, NK-1 was present in all the types of pituitary tumors, and a
      total of 33 (60.0%) contained NK-1 positive tumor cells. The frequency of NK-1
      immunoreactivity in the individual adenoma types was; 14 of 16 GH producing
      adenomas (87.5%), 7 of 14 PRL producing adenomas (50%). 3 of 4 TSH producing
      adenomas (75%), 3 of 5 ACTH producing adenomas (60%), and 5 of 16 nonfunctioning
      adenomas (31.3%). By double immunostaining, NK-1 was found to be frequently
      colocalized with ACTH in ACTH producing adenomas, and was colocalized with PRL in
      PRL producing adenomas, or with GH, PRL or the alpha-subunit in GH producing
      adenoma cells. NK-1 immunoreactive cells were observed in close association with
      S-100 immunopositive FS cells in the adenomas. Our results may indicate that NK-1
      positive cells may have functions as a paracrine modulators of their neighboring
      cells, which includes S-100 positive FS cells.

PMID- 9266439
TI  - Prolonged treatment with biologic agents for malignant glioma: a case study with
      high dose tamoxifen.
AB  - Traditional study design for treatment of malignant gliomas does not allow tumor
      progression to be greater than 25-50 percent without terminating treatment. This
      design may prevent recognition of patients who benefit from the treatment either
      by slowed growth or delayed response. A delayed response or slowed growth may be
      characteristic of biologic agents being evaluated in the treatment of malignant
      glioma. Because of the low toxicity of certain biologic drugs, continued
      treatment through tumor growth can be ethically considered in study design. The
      effect of biologic agents on a neoplasm may include cellular differentiation,
      retardation of growth, cytostasis, cytocidal effects, or apoptosis. Such effects
      may clinically translate into a complete response, partial response, stable
      disease or retardation of growth with or without an eventual reduction of tumor.
      We present a patient with a recurrent malignant glioma who was continued on high
      dose tamoxifen despite radiologic documented doubling of the tumor size and who
      eventually showed a delayed response to this agent nine months after initiation
      of treatment. Strong consideration should be given to the prolonged treatment of
      non-toxic biologic agents in a controlled clinical trial, where agents have shown
      some benefit in phase one studies.

PMID- 9266440
TI  - Prospective study of paclitaxel-induced peripheral neuropathy with quantitative
      sensory testing.
AB  - BACKGROUND: Paclitaxel-induced peripheral neuropathy (PN) may be severe and dose
      limiting at initial doses > or = 275 mg/M2, but its neurotoxicity at doses < or =
      250 mg/M2 has been incompletely characterized. The purposes of this study were to
      characterize and quantify paclitaxel-induced PN and to determine the utility of
      quantitative sensory testing (QST). METHODS: We prospectively examined clinically
      and by QST 37 women with metastatic breast cancer, treated with paclitaxel (200
      250 mg/m2) (average number of cycles = 7.3 over an average of 20.1 weeks). QST
      included thermal threshold (TT) and vibration threshold (VT). RESULTS:
      Paresthesias appeared in 31 (84%) patients after an average of 1.7 cycles and an
      average cumulative dose of 371.5 mg/M2. Symptoms occurred after the first or
      second dose in 26 (84%) patients and then stabilized in 10 (32%), improved in 13
      (42%) despite continued treatment, resolved completely in 6 (19%), and were
      progressive in 2 (7%). Paclitaxel was discontinued in only 1 (3%) patient because
      of neurotoxicity and no patient required dose reduction because of PN. Thirty-six
      (97%) developed signs of PN. The most sensitive QST was great toe VT but QST did
      not predict or identify subclinical PN in any patient. Neurologic syndromes other
      than PN developed in 12 (32%) patients, and 7 were due to metastatic cancer.
      CONCLUSIONS: 1) Paclitaxel-induced PN is mostly sensory, and begins after the
      first or second dose. At these doses the neuropathy is mild, and rarely dose
      limiting. 2) QST quantified the neuropathy but was less sensitive than the
      clinical examination. 3) Knowledge of the features of paclitaxel's PN allows it
      to be differentiated from other neurologic syndromes which may signal tumor
      progression.

PMID- 9266441
TI  - Carcinomatous meningitis secondary to breast cancer: predictors of response to
      combined modality therapy.
AB  - PURPOSE: To identify the factors predictive of response and increased survival in
      patients with leptomeningeal metastases (LM) from breast cancer receiving multi
      modal therapy. BACKGROUND: Leptomeningeal metastases (LM) are being diagnosed
      with increasing frequency as anti-cancer therapies become more effective and
      result in prolonged patient survival. PATIENTS AND METHODS: 32 women (range 28 to
      74 years; median 49) with LM due to metastatic breast cancer were treated.
      Neurologic presentation included: cranial neuropathies (10 patients); headache
      (10); cauda equina syndrome (6); ataxia (6); meningismus (3); radioculopathy (2);
      myelopathy (2); confusion (2); and seizure (1). All patients underwent
      radiographic evaluation of the extent of CNS disease followed by radiotherapy (21
      women) and intraventricular chemotherapy: (methotrexate 32 women; cytarabine 22;
      thio-TEPA 11). RESULTS: CNS imaging (cranial MR, spine MR and radionuclide
      ventriculography) demonstrated: interrupted CSF flow (21); subarachnoid nodules
      (8); parenchymal brain metastases (6); hydrocephalus (4); and epidural spinal
      cord compression (1). Cytologic responses were seen in 14 women to first-, 7 to
      second- and 3 to third-line chemotherapy. Treatment-related toxicity included 21
      women with aseptic meningitis and 10 women with thrombocytopenia or neutropenia
      (5 related to intraventricular chemotherapy). Median survival was 7.5 months
      (range 1.5 to 16), 18 women died of progressive LM or combined LM and systemic
      disease progression. Women with persistent interruption of CSF flow fared worse
      than women with normal CSF flow (median survival 3 versus 10 months; p < 0.0001).
      CONCLUSION: LM in women with metastatic breast cancer may be palliated with
      combined modality therapy, however, success of therapy and survival is based upon
      pre-treatment CNS extent of disease evaluation.

PMID- 9266442
TI  - Parenchymal damage in the territory of the anterior choroidal artery following
      supraophthalmic intracarotid administration of CDDP for treatment of malignant
      gliomas.
AB  - We treated ten patients with malignant glioma by intracarotid chemotherapy with
      cis-diamminedichloroplatinum (CDDP) and/or 3-(4-amino-2-methyl-5
      pyrimidinyl)methyl-1-(2-chloroethyl)-3-nitrosourea (ACNU). Three of the patients
      who underwent supraophthalmic intracarotid infusion of CDDP developed a low
      density area in the basal ganglia on CT scan or an enhancing lesion in the
      hypothalamic region on MRI, with or without neurologic symptoms. No patient had
      such complications with supraophthalmic infusions of ACNU, or with cervical
      intracarotid infusion of CDDP or selective infusion of CDDP via the anterior or
      middle cerebral arteries. Supraophthalmic intracarotid administration of CDDP may
      augment drug delivery to tumors and prevent visual complications, but is
      accompanied by considerable risk of parenchymal damage in the territory of the
      anterior choroidal artery. Possible mechanisms for such complications are
      discussed.

PMID- 9266443
TI  - Clinical trial of external beam-radiotherapy combined with daily administration
      of low-dose cisplatin for supratentorial glioblastoma multiforme--a pilot study.
AB  - This trial tested the assumed efficacy and safety of external beam-radiotherapy
      combined with daily administration of low dose cisplatin (CDDP) (ERCLC therapy)
      for patients with glioblastoma multiforme (GBM). Thirty adult patients with
      supratentorial GBM received daily postoperative treatment with low dose
      intravenous CDDP (4-6 mg/m2) administered 30 minutes before external irradiation.
      In 10 patients, intraoperative radiotherapy (IORT) following surgery was given
      prior to ERCLC therapy. Tumor response on MRI, interval to tumor progression,
      survival, and toxicities were analyzed. None of the patients showed a tumor
      response to ERCIC therapy. Overall, the median time to tumor progression was 6
      months with a 1-year tumor progression-free rate of 26.7% and a 2-year rate of
      0%. The median survival time was 15 months with a 1-year survival rate of 69.9%
      and a 2-year rate of 31.5%. The survival rate of patients with IORT was better
      than that of those without IORT, however, there was no significant difference.
      Anorexia associated with nausea occurred in 70% and general fatigue in 10.0%.
      Leukopenia and thrombocytopenia occurred in 26.7% and 33.3%, respectively.
      However, none of the patients had to be withdrawn from therapy due to these
      toxicities. Other toxicities were not observed. This clinical study showed that
      daily administration of low dose CDDP did not enhance tumor response to
      irradiation for GBM on MRI. Regarding toxicity, however, ERCLC therapy was well
      tolerated. Although this trial did not provide sufficient data to determine
      whether ERCLC therapy was effective for GBM due to the small number of patients,
      additional clinical trials of this therapy may be warranted because that the
      survival rate in this study was equal to the better results recently reported for
      newly diagnosed GBM.

PMID- 9266444
TI  - Hematogenous metastases of the human brain--characteristics of peritumoral brain
      changes: a review.
AB  - The brain is an important site of hematogenous metastases from malignant tumors
      in other organs. The effects on the brain is a combination of tissue destruction
      induced by invading tumor cells and reactive alterations occurring around the
      metastases. This review focuses on neuropathological changes around hematogenous
      metastases of the human brain. The peritumoral brain parenchyma shows structural
      and functional changes of the intracerebral microvessels and edema. The
      endothelial cells of peritumoral microvessels express glucose transporter protein
      (GLUT 1) in the same way as the normal brain. Reduction in immunostaining to GLUT
      1 may occur in the microvessels located within the metastases. This would
      indicate abnormalities of the blood-brain barrier in tumor vessels but normal
      barrier function in the peritumoral region. Reactive astrocytes and activated
      microglial cells are both involved in the process of peritumoral gliosis.
      Activated glial cells produce numerous biological active compounds including
      endothelin-1 which after release from such cells can influence the structure and
      function of the peritumoral brain tissue. Lesions of oligodendrocytes and edema
      may be implicated in myelin degeneration. Finally, metastases will induce axonal
      and neuronal injuries as indicated by a recent study on expression of beta
      amyloid precursor protein (beta APP) in reactive axonal swellings.

PMID- 9266445
TI  - Immunoreactivity of human MAb BT32/A6 with neuroepithelial tumors.
AB  - The present study was undertaken to determine the pattern of immunoreactivity of
      BT32/A6, a human IgM monoclonal antibody (MAb), with the following histological
      panels: 1) 30 human and non-human cell lines, 2) 32 normal human tissues, and 3)
      28 tumors of central neuroepithelial origin (16 astrocytic; 11 non-astrocytic).
      Antibody BT32/A6 recognizes a surface and cytoplasmic antigen present on a
      variety of human tumor cell lines including gliomas, melanomas, neuroblastomas,
      and a few sarcomas. The antigen is present (at least focally) on 15/16 astrocytic
      tumor tissue sections (94%), and in some cases, on close to 100% of cells. All
      malignant cell types, including small anaplastic cells, giant cells, gemistocytic
      cells, and cells forming pseudopalisades were labeled by MAb BT32/A6. Non
      astrocytic neuroepithelial tumors did not stain appreciably with MAb BT32/A6.
      There was weak immunoreactivity in a small subset of normal human tissues of
      epithelial and lymphoid origin, with the exception of adrenal cortex, which
      exhibited weak to moderate staining. All normal tissues of neuroectodermal and
      mesenchymal origin were unreactive. In conclusion, MAb BT32/A6 appears to be
      unique in that it recognizes a highly-expressed astrocytic tumor-associated
      antigen that is present on both low and high grade tumors. This makes it a strong
      candidate for further studies aimed at establishing its usefulness in the
      treatment of human astrocytic tumors.

PMID- 9266446
TI  - Pharmacokinetics and acute toxicology of intraventricular 131 I-monoclonal
      antibody targeting disialoganglioside in non-human primates.
AB  - Tumors metastatic to the leptomeninges are often incurable despite current
      aggressive treatment modalities. Regional therapy by intrathecal administration
      of monoclonal antibodies (MoAbs) can maximize their concentration to tumor sites
      while reducing systemic toxicities. Anti-GD2 antibody 3F8 has successfully
      targeted human neuroectoderm derived tumors. Disialoganglioside GD2 expression in
      the central nervous system is identical between humans and cynomolgus monkeys. We
      studied the pharmacokinetics and the acute and subacute toxicities of
      intraventricular 131I-3F8 in 8 cynomolgus monkeys. Four animals were purposely
      immunized with intravenous 3F8 administered 2-4 weeks prior to injections. All
      animals remained clinically stable. Toxicities included weight loss, fever and
      CSF leukocytosis. One animal developed a left-sided hemiparesis following his
      seventh injection, presumably due to a local drug accumulation in the setting of
      an intermittently patent catheter. The estimated radiation dose to the CSF was 19
      48 Gy in the immunized monkeys and 19-82 Gy in the nonimmunized monkeys, and to
      blood was 0.11-0.98 Gy and 0.29-2.03 Gy, respectively. Histopathology revealed
      chronic reactive changes adjacent to the region of catheter placement and a focal
      vasculitis in 2 animals. Peripheral blood counts and bone marrow examinations
      remained normal. Because of the blood-brain barrier, CSF monkey-anti-mouse
      antibody titers were less than 10 per cent of those in the serum. In contrast to
      the CSF radioactivity clearance which was similar in all animals, blood clearance
      was substantially accelerated in 3F8-immunized animals versus controls.
      Correspondingly, the CSF to blood dose ratio was improved 1.3 to 6.6 fold (mean
      3.5). We conclude that intraventricular administration of 131I-3F8 in primates is
      tolerable. It can deliver very high doses of radiation to the CSF space with
      minimal toxicity to blood and bone marrow. Serum anti-mouse antibody accelerates
      the clearance of 131I-3F8 in blood and may improve the therapeutic index.

PMID- 9266447
TI  - Analyses of human gliomas by restriction landmark genomic scanning.
AB  - The 16 primary gliomas were examined for changes in genomic DNA using a recently
      developed 2-dimensional gel electrophoresis method called restriction landmark
      genomic scanning (RLGS). This approach allows detection of DNA amplification,
      deletion, methylation and potentially other genetic rearrangements represented as
      decreases and increases in spot/fragment intensity on an autoradiogram.
      Approximately 2,000 landmark sites in tumor DNA were compared with those of DNA
      isolated from normal brain tissues. Seven spots showing intensified signal were
      consistently detected in at least 50% of tumors, implying activation of
      corresponding DNA sequences, and 8 additional spots having reduced signal were
      observed, again in more than 50% of all tumors, suggesting inactivation by the
      loss of 1 allele or homozygous deletion. Decreased signal may also infer relative
      CpG island methylation state. Of those spots consistently identified in tumors, 2
      amplified and 4 reduced spots were found to be characteristic of low- and high
      grade tumors, while the remaining 5 amplified and 4 reduced spots were associated
      with high-grade gliomas only, suggesting a link of specific mutations to degree
      of malignancy. A separate subset of glioblastomas evaluated, however, showed no
      alterations in these 'hot spots' which were detected in even low grade
      astrocytomas. The results demonstrate the genetic heterogeneity of glioblastoma
      and implicate the progression of neoplasia via differing genetic pathways.

PMID- 9266448
TI  - Intra-arterial carboplatin chemotherapy for brain tumors: a dose escalation study
      based on cerebral blood flow.
AB  - PURPOSE: To perform in intra-arterial dose escalation study of carboplatin based
      on hemispheric blood-flow estimation in patients with recurrent malignant glioma.
      The primary purpose was to determine the maximally tolerated intra-arterial dose.
      METHODS AND PATIENTS: Methods included: 1) selective intra-arterial delivery
      performed with modern microcatheters, 2) pulsatile infusion, and 3) dosage based
      on local cerebral blood-flow estimation (middle cerebral artery 60%, anterior
      cerebral artery 20%, posterior cerebral artery 15%, and anterior choroidal artery
      5% of the hemispheric blood-flow). The deliveries were performed above the
      ophthalmic artery in the anterior circulation, or above the anterior inferior
      cerebellar arteries in the posterior circulation. The doses were escalated from
      200 mg/hemisphere at 50 mg increments. Twenty-one patients were studied (14 with
      glioblastoma multiforme, five anaplastic astrocytoma, one aggressive low-grade
      glioma, one metastasis). Patients had recurrent glioma limited to one hemisphere
      and Karnofsky score of 50 or greater. Concomitant therapies were allowed.
      RESULTS: Carboplatin was escalated to a dose of 1400 mg/hemisphere. One patient
      had a permanent neuromotor decline. The predominant toxicity was hematopoietic.
      The median time to tumor progression was 22 weeks, median survival 39 weeks, and
      the response rate 70% (50% SD and 20% PR) of 19 patients. CONCLUSIONS:
      Hemispheric blood-flow estimation allowed us to escalate the dose of intra
      arterial carboplatin to twice what was previously considered safe. Responses
      compared favorably to previous studies. Further studies are needed to determine
      if this method will provide improved and durable responses.

PMID- 9266449
TI  - Primary intracranial fibrosarcoma with intratumoral hemorrhage: neuropathological
      diagnosis with review of the literature.
AB  - Primary intracranial sarcomas are rare tumors of mesenchymal origin in the
      central nervous system (CNS). Spontaneous hemorrhage, while not an uncommon
      presentation of brain tumors, has not been described in primary cerebral sarcoma.
      We report the case of a 43 year old woman presenting with spontaneous hemorrhage
      into a primary cerebral fibrosarcoma, and discuss this case in the context of the
      diagnostic criterions of these rare tumors previous reports of intracranial
      sarcomas and mechanisms of intratumoral hemorrhage.

PMID- 9266450
TI  - Solitary meningeal recurrence in a patient with transitional cell carcinoma of
      the bladder with locally bulky disease at presentation.
AB  - Patients with locally advanced transitional cell carcinoma (TCC) of the bladder
      are at high risk for systemic relapse, with liver, bone and lung being the
      commonest sites of metastases. We report the case of a 52-year-old woman with a
      solitary meningeal relapse, a rare site of recurrence, after 8 months of complete
      remission obtained with M-VEC for locally advanced TCC of the bladder. We
      speculate on the likely risk factors related to this unusual site of recurrence.

PMID- 9266451
TI  - Phase II trial of cisplatinum and etoposide in brain metastases of solid tumors.
AB  - Fourteen patients with brain metastases (BM) of solid tumors received intravenous
      cisplatinum, 40 mg/m2/day and etoposide, 150 mg/m2/day, for 3 days every 3 weeks.
      Primary tumors were lung (8 patients), breast (4), colon (1), and stomach (1).
      Two patients responded (1 complete response in a poorly differentiated lung
      cancer patient and 1 partial response in a breast cancer patient). The overall
      response rate was 14%, with a median survival of 6 months. Main toxicity was
      grade 3-4 neutropenia that occurred in 36% of patients. There were no toxic
      related deaths. Chemotherapy as a single therapeutic regimen seems not to be an
      effective treatment for BM from relatively resistant solid tumors. Moreover, it
      produces rather high, although not life-threatening, hematologic toxicity.

PMID- 9266452
TI  - Melanotic schwannoma of the sympathetic ganglia: a histologic,
      immunohistochemical and ultrastructural study.
AB  - We describe the case of a 46-year-old male patient who presented with pain in the
      left thigh, often accompanied by lumbar pain. These symptoms were sustained by a
      neoplasm, which was located in the sympathetic ganglia, at the level of the 3rd
      left lumbar spinal root and which was completely excised. Immunohistochemical
      positivity for S100, HMB45, and NSE antibodies suggested that the lesion was a
      melanotic schwannoma (MS), with both schwannian and melanocytic differentiations,
      the latter containing melanosomes at ultrastructural examination. Non-recurrence
      after 16 months of follow-up further supports our diagnosis of MS.

PMID- 9266453
TI  - Efficacy and safety of prophylactic cranial irradiation in patients with small
      cell lung cancer.
AB  - BACKGROUND: Prophylactic cranial irradiation (PCI) as part of the treatment
      regimen for patients with limited stage small cell lung cancer (SCLC) remains
      controversial. The present study was performed to analyze the efficacy and safety
      of PCI in patients with limited stage SCLC who achieved complete remission.
      PATIENTS AND METHODS: Between 1983 and 1993, thirty-nine patients with limited
      stage SCLC who had shown complete remission after chemotherapy were enrolled
      prospectively into the non-randomized study. Eighteen of them received PCI
      (PCI+), while 21 did not (PCI-). Pretreatment CT or MRI of the brain was
      performed in all patients. Patients were prospectively evaluated by a neurologist
      at regular intervals. RESULTS: Three PCI+ patients and seven PCI- patients
      developed brain metastases. The frequencies of brain metastases were not
      significantly different between the groups (Fisher's exact test, p = 0.207), but
      brain metastases in PCI+ patients tended to occur later (log rank, p = 0.008).
      Overall survival was significantly longer in PCI+ patients (log rank, p < 0.001).
      Early toxicity consisted of headache, nausea, fatigue, concentration problems and
      alopecia. These symptoms and signs were mild and usually reversible within a few
      months. Late toxicity was studied in patients whose survival exceeded two years.
      Seven PCI+ patients survived for more than two years, while no PCI- patients
      survived for more than two years. Memory problems were seen in six of the seven
      patients. These problems were non-disabling and, once established, remained
      stable for months to years. The most prominent radiologic abnormalities were
      cortical atrophy and leukoencephalopathy, found in four of the five patients who
      underwent radiologic follow-up examination. CONCLUSIONS: This non-randomized
      study suggests that PCI may be effective by decreasing the frequency of brain
      metastases and by increasing the brain metastasis-free survival and overall
      survival, with a minor risk of clinical and radiologic neurotoxicity.

PMID- 9266454
TI  - Treatment and outcome of brain metastasis as first site of distant metastasis
      from breast cancer.
AB  - Twenty-eight consecutive patients with breast cancer were analyzed who presented
      with a single brain metastasis as first site of distant metastasis. The response
      to surgery with postoperative radiation therapy (RT) (9 patients) and to non
      surgical therapy as first-line treatment was 100% and 89% respectively with a
      significant difference in median recurrence-free intervals of 23 months and of 5
      months respectively (p = 0.033). Retreatment of a local relapse by surgery (+/
      RT, +/-chemotherapy) or by non-surgical treatment resulted in a response in 6 of
      the 7 operated patients and in 5 of the 6 non-operated patients with a median
      duration of response of 7 months (range 2-20 months) and of 3 months (range 2-4
      months) respectively. The overall median survival of the 28 patients with a
      single brain metastasis was 16 months (range 2-39 months). The median survival in
      the primarily operated patients was 23 months, in the primarily not-operated
      group 10 months, and in the never-operated group 9 months. In comparison, the
      response to non-surgical treatment in 20 consecutive patients who presented with
      multiple brain metastases as first site of distant metastasis was 55% with a
      median recurrence free interval of 4 months. The median survival in this group
      was 4 months, which was significantly shorter than survival of patients with
      single brain metastasis (p = 0.0036). These results suggest that breast cancer
      patients with a single brain metastasis as first presentation of relapse
      constitute a specific subgroup with a favorable response to treatment and a long
      survival especially if they can be treated by surgery with postoperative RT.

PMID- 9266456
TI  - Boron neutron capture therapy: preliminary study of BNCT with sodium borocaptate
      (Na2B1 2H1 1SH) on glioblastoma.
AB  - To plan the optimal BNCT using BSH for glioblastoma patients, the 10B
      concentration in tumor and blood was investigated in 11 newly diagnosed
      glioblastoma patients. All patients received 20 mg BSH/kg body weight 2.5-16 hrs
      prior to tumor removal. The quantitative distribution of 10B was determined by
      prompt gamma ray spectrometry and/or alpha-track autoradiography. 10B
      distribution in tumors was heterogeneous, +/- 25% of scattering at the
      microscopic level, and the distribution was also heterogeneous at the tissue
      level. 10B concentration in blood decreased in bi-exponential decay as a function
      of the time after the end of the administration. The T/B ratio showed non
      exponential increase with large variation. The maximum T/B ratio would be around
      1. The tumor/normal brain (T/N) ratio of 10B concentration was 11.0 +/- 3.2. The
      10B content in normal brain is originated in vascular 10B in parenchyma, since
      the 10B content in normal brain to blood (N/B ratio) being compatible with the
      blood content in parenchyma. These values allow for BNCT, using thermal neutrons,
      on brain tumors located less than approximately 3.3 cm in depth from the brain
      surface of neutron incidence, providing that the dose on the normal endothelium
      is controlled to less than the tolerance limit. In our preliminary study of BNCT,
      a 31% 3-year survival was achieved over all for 16 glioblastoma patients and a
      50% 2-year survival was achieved on 8 glioblastoma patients in our recent dose
      escalation study based on these data.

PMID- 9266455
TI  - Is medulloblastoma the same tumor in children and adults?
AB  - The appearance of medulloblastoma in adult age and the uncertain overlapping of
      prognostic factors in pediatric and adult populations stimulate the question of
      whether medulloblastoma is different in adults and in children. The pathologic
      features, proliferation potential and glial/neuronal differentiation have been
      investigated in 42 adult medulloblastomas and 42 medulloblastomas of children;
      the quantitative data have been compared between the two groups of age. Homer
      Wright rosettes, nuclear polymorphism and histologic signs of neuronal
      differentiation were more frequent in children cases; GFAP-positive tumor cells
      and desmoplastic type were more frequent in adult cases. The mean, median and
      rage of Lis, with PCNA and MIB-1 were significantly (p < 0.05) higher in adults
      than in children. All cases, independently from age of the patients were
      immunoreactive with markers of neuronal commitment (class III beta tubulin
      isotype, MAP-2, neurofilaments). The immunoreactivity pattern suggested a more
      mature neuronal character in desmoplastic cases of adults than of children and in
      classic cases of children than of adults. In conclusion, some phenotypic
      differences between childhood and adult medulloblastoma exist, but do not support
      a substantially different course of the disease. The higher proliferation
      potential in adult than in childhood cases is unexpected in a tumor of embryonal
      origin, and reduces the applicability of Collin's law to medulloblastoma.

PMID- 9266457
TI  - Idiopathic generalized epilepsies with typical absences.
AB  - Idiopathic generalized epilepsy (IGE) comprises several subsyndromes. These are
      principally: benign neonatal familial convulsions, benign neonatal convulsions,
      benign myoclonic epilepsy in infancy, childhood absence epilepsy, juvenile
      absence epilepsy, juvenile myoclonic epilepsy, epilepsy with generalised tonic
      clonic seizures on awakening. In addition, there are less well-recognized
      syndromes, such as eyelid myoclonia with absences. The pathophysiology of the IGE
      syndromes is not fully understood; it is evident that typical absences are the
      result of abnormal oscillations between the thalamus and cerebral cortex. Genetic
      studies are in progress to elucidate the biochemical defects underlying the
      conditions. The clinical and electroencephalographic features of the individual
      subsyndromes are distinct, but some patients may be difficult to classify into a
      particular subgroup. A correct syndromic diagnosis is important, as treatment
      strategies differ for patients with the different forms of IGE, and it is
      necessary for genetic research.

PMID- 9266458
TI  - Is unilateral spatial neglect a single phenomenon? A comparative study between
      exploratory-motor and visual-counting tests.
AB  - The aim of this study is to report the preliminary findings of a traditional
      battery of tests and our original battery capable of assessing the presence of
      components and extent of lesions in patients with unilateral spatial neglect.
      Thirty patients who had unilateral spatial neglect with a stroke in the right
      hemisphere were assessed for unilateral spatial neglect on exploratory-motor (E
      M) tasks, visual-counting (V-C) tasks, and traditional neglect batteries at least
      4 weeks after the onset. Other neuropsychological tests and computed tomography
      were also performed to investigate the relationship with neglect. A factor
      analysis showed that our tasks loaded significantly on three factors. E-M neglect
      was found in 16 patients, and V-C neglect in 22 patients with unilateral spatial
      neglect. There were high correlations between E-M neglect and motor paralysis,
      word fluency, backward digit span and motor impersistence. There were high
      correlations between V-C neglect and visual-field defect, line bisection, line
      cancellation and figure copying. Lesions in the frontal lobe, caudate, insula,
      and anterior portion of the paraventricular white matter were commonly associated
      with E-M neglect. Lesions in the occipital lobe were also associated with V-C
      neglect. We suggest that unilateral neglect is not a single phenomenon, but
      rather involves several different components. We propose that E-M and V-C tasks
      are useful methods for evaluating the extent of lesions in patients with
      unilateral spatial neglect.

PMID- 9266459
TI  - T-cell tumour necrosis factor-alpha receptor binding in demented patients.
AB  - Dementia of Alzheimer type (DAT) is a neurodegenerative disease of the central
      nervous system (CNS), in which an unbalanced cytokine network may lead to an
      altered immunoregulation. Tumour necrosis factor (TNF)-alpha is a cytokine with
      manifold effects on the neuroimmune system. Specific TNF-alpha receptors have
      been found on human peripheral blood lymphocytes. The aim of the present study
      has been to assay TNF-alpha binding on T cells from DAT patients and healthy sex-
      and age-matched controls. We found that T lymphocytes from demented patients bear
      significantly more p60 and p80 TNF-alpha receptors than those from controls
      (Bmax: 705, 29 vs 131, 6 (mean, SEM) receptors/cell). Such TNF-alpha binding
      sites, of the same type in DAT patients and healthy subjects (Kd: 67.6, 5.0 vs
      70.7, 5.6 (mean, SEM) pM), are functional, since they are able to mediate in
      vitro NF-kappa B activation. These results are discussed in terms of DAT
      pathogenesis. Since it has been reported that activated T cells have more TNF
      alpha receptors than resting cells, an increased number of lymphocyte TNF-alpha
      receptors might indicate a systemic immune activation in DAT patients as compared
      with healthy controls.

PMID- 9266460
TI  - Intrafamilial heterogeneity of movement disorders: report of three cases in one
      family.
AB  - We report three members of a single family with an apparently autosomal dominant,
      nonparoxysmal, hyperkinetic movement disorder with onset in adolescence. The
      proband, a 56-year-old woman, manifested dystonia, tremor and myoclonus; one of
      her daughters exhibited myoclonus with tremor, and the other demonstrated
      myoclonus with chorea later accompanied by tremor and dystonia. The slowly
      progressive but not debilitating symptoms were restricted to the head, arms and
      hands and were only moderately affected by alcohol. Laboratory investigations
      failed to identify any abnormality, and linkage analysis excluded the region
      containing the DYT1 locus, indicating that the gene responsible for idiopathic
      torsion dystonia was not implicated in this family. While this disorder shares
      manifestations with myoclonic dystonia, essential myoclonus and benign chorea,
      the marked intrafamilial heterogeneity and the sex-limited phenotype expressed
      only in females of two generations appear to be unique.

PMID- 9266461
TI  - The use of percutaneous endoscopic gastrostomy (PEG) feeding tubes in patients
      with neurological disease.
AB  - Percutaneous endoscopic gastrostomy (PEG) is being used increasingly in the
      treatment of patients with neurogenic dysphagia to improve nutrition and prevent
      choking and aspiration pneumonia. PEG is used in a wide range of general medical
      conditions, but its role in clinical neurology is sometimes controversial. This
      paper reviews the place of PEG in the management of 32 patients with a variety of
      chronic and progressive neurological disorders. All the patients found it to be
      an effective and acceptable method of feeding that prevented weight loss, reduced
      chest infections, facilitated nursing care and improved their quality of life.
      PEG has an important role in neurological rehabilitation.

PMID- 9266462
TI  - Meningitis due to viridans streptococci in adults.
AB  - Seven patients are reported with meningitis due to viridans streptococci. These
      patients represented 5% of culture-proven cases of bacterial meningitis in adults
      participating in a prospective multicentre clinical trial evaluating the use of
      dexamethasone. Meningitis was iatrogenic in three patients: one patient had been
      treated with endoscopic sclerotherapy for oesophageal varices, and two patients
      had undergone thermocoagulation of the gasserian ganglion for trigeminal
      neuralgia in the previous days.

PMID- 9266463
TI  - The genetics of localization-related symptomatic epilepsy: risk of a family
      history with seizures in patients who have undergone surgery.
AB  - A family history of epileptic seizures including febrile convulsions was found in
      15 of 103 patients (15%) with localization related epilepsy with partial seizures
      with and without secondary generalization, who were operated on because of drug
      resistance. This rate was significantly higher than that of the cumulative
      incidence in the general population (4%). The localization of the brain damage
      did not play a role (temporal lobe resection left: 15%, right: 17%, extra
      temporal lesion excision: 20%, hemispherectomy: 11%). Various family members were
      involved. Some patients had more than one relative with seizures. Thus, 21
      relatives suffered from seizures. Eleven of them had generalized tonic-clonic
      seizures (one grand mal on awakening), 7 had febrile convulsions (4 complicated),
      and in 1 patient the grand mal seizures on awakening were preceded by absences; 1
      had generalized tonic-clonic and complex partial seizures; 1 after complicated
      febrile seizures likewise had complex partial seizures; another mentally retarded
      patient suffered from generalized tonic-clonic, axial tonic and myoclonic-astatic
      seizures. The seizure type of 3 remote relatives was not known. The first seizure
      occurred in 16 family members during childhood, in 3 in adolescence and in only 1
      in adulthood (1 unknown). Eight showed mental retardation of slight degree in
      most. It is interesting that only one-third of the patients with a family history
      with seizures were seizure-free after the operation; 5 still had seizures, mostly
      reduced in frequency, 3 had seizures and isolated auras and 2 had only isolated
      auras. On comparing the findings in patients with and without a family history
      with seizures, those with family members with epileptic seizures showed a lower
      rate of an intellectual deficit (7 vs 47%) and brain tumours (13 vs 44%). Our
      earlier findings with a different group of patients are thus confirmed: that
      genetics play a role in symptomatic epilepsies.

PMID- 9266464
TI  - Dominantly inherited leukodystrophy showing cerebellar deficits and spastic
      paraparesis: a new entity?
AB  - We studied a dominant hereditary disorder showing progressive spastic
      paraparesis. The symptoms began in early childhood, with cerebellar deficits and
      mild mental deterioration, and the subsequent appearance of limb spasticity
      resulted in severe disability in the 3rd-4th decades of life. None of the
      patients were associated with any somatic abnormalities. Brain MRI showed diffuse
      white-matter involvement in all affected patients, but not in unaffected
      siblings. Although dominant, recessive, or X-linked leukodystrophies cause
      similar clinical features, our family did not show any known biochemical or gene
      deficits characteristic of these disorders. The clinical, radiological, and
      biochemical findings of this family are reported and suggest a possible novel
      genetic disorder.

PMID- 9266465
TI  - Human herpes virus 6 and human herpes virus 8 DNA sequences in brains of multiple
      sclerosis patients, normal adults and children.
AB  - In order to determine whether the newly discovered human herpesviruses (HHVs) are
      involved in multiple sclerosis (MS), we investigated by polymerase chain reaction
      the presence of specific deoxyribonucleic acid (DNA) sequences belonging to human
      herpesvirus 6 (HHV-6) and to human herpesvirus 8 (HHV-8), in the peripheral blood
      mononuclear cells (PBMCs), and in the brain and spinal cord plaques from MS
      patients. Normal adult and stillborn children's brains were investigated as
      controls. PBMCs from 56 MS patients contained HHV-6 DNA in only 3 cases and in
      none were there HHV-8 sequences. The cerebral DNA from 5 MS patients was positive
      for HHV-8 and not for HHV-6 sequences, while the nervous tissue of one patient
      who died with neuromyelitis optica was positive for HHV-6 and negative for HHV-8.
      The brains of 4/8 adult controls were positive for HHV-6, as were 3/8 for HHV-8;
      none of the 7 stillborn children's cerebral tissue contained HHV-6 sequences,
      while 2 contained HHV-8 DNA. Although these data do not support a hypothesis that
      there is a role for these two HHVs in the pathogenesis of MS, nevertheless it may
      be suggested that (1) the two viruses possess strong neurotropism and the central
      nervous system seems to be a reservoir for them (2) HHV-6 infection is probably
      not transmitted maternally, but is acquired later in infancy.

PMID- 9266466
TI  - Plasticity of the spinal cord contributes to neurological improvement after
      treatment by cervical decompression. A magnetic resonance imaging study.
AB  - To investigate the relationship between morphological plasticity of the spinal
      cord and neurological outcome after surgery for compressive lesions, we
      correlated the transverse area of the cervical spinal cord measured by transaxial
      magnetic resonance imaging (MRI) obtained during the early postoperative period
      (1-6 months) with neurological function assessed at a median postoperative follow
      up period of 2.5 years. Measurements on MRI in 56 patients (35 men and 21 women)
      included evaluation of the cross-sectional area of the cervical cord and the
      subarachnoidal space at the level of decompression. The transverse area of the
      cervical cord increased by 30 to 62% postoperatively and that of the
      subarachnoidal space by 57 to 95%. Neurological improvement was noted in all
      patients and averaged 63% in our assessment scale. Expansion of the cervical cord
      during the early postoperative period correlated significantly with the late
      postoperative neurological status (P = 0.009). Our results suggest that an
      increase in the cross-sectional area of the cervical spinal cord, representing
      spinal cord morphological plasticity, is a significant factor in determining the
      late neurological improvement following decompressive surgery.

PMID- 9266467
TI  - Upside-down reversal of vision in multiple sclerosis.

PMID- 9266468
TI  - Pulsed high-dose dexamethasone treatment of polyneuropathy associated with
      monoclonal gammopathy.

PMID- 9266469
TI  - Nerve biopsy findings in hemizygous and heterozygous patients with Fabry's
      disease.

PMID- 9266470
TI  - Maternally inherited diabetes and deafness with cerebellar ataxia: a new clinical
      phenotype associated with the mitochondrial DNA 3243 mutation.

PMID- 9266471
TI  - Delayed-onset hemidystonia secondary to herpes zoster ophthalmicus-related
      intracerebral arteritis in an adolescent.

PMID- 9266472
TI  - Insect neuropeptide proctolin and its analogues. An overview of the present
      literature.
AB  - In the present paper, the literature describing synthetic, biological and
      conformational studies on the insect neuropeptide proctolin (H-Arg-Tyr-Leu-Pro
      Thr-OH) and its analogues is summarized. The paper covers proctolin and its 80
      analogues modified in positions 1-5, a cycloanalogue and analogues with a
      truncated or elongated peptide chain. These peptides were bioassayed by different
      methods, e.g. studies of myotropic activities in several insect species in vitro
      and behaviour in rats in vivo. Based on these data structure-activity
      relationships are discussed.

PMID- 9266473
TI  - Stability of protease inhibitors based on the Bowman-Birk reactive site loop to
      hydrolysis by proteases.
AB  - Bowman-Birk proteinase inhibitor proteins contain two inhibitory regions, each of
      which is encapsulated within nine-residue disulfide-linked loops. It is known
      that short cyclic peptides that retain the nine-residue disulfide-bridged motif
      have inhibitory activity, and can be used as models of the natural inhibitor
      protein. Two factors are important in determining the effectiveness of such
      inhibitor peptides: the value of the inhibition constant, and rate at which the
      inhibitor peptide is hydrolyzed by the proteinase. In this paper we report a
      study of the inhibitory properties and stability towards proteolytic hydrolysis
      of a family of synthetic peptides derived from the trypsin reactive site loop of
      the Bowman-Birk inhibitors. The addition of a single amino acid residue to each
      end of the nine-residue disulfide-linked loop is found to reduce the rate at
      which the peptide is hydrolyzed. In addition, changing the P2' residue from Asn-
      >Ile gives inhibitors with considerably enhanced stability to proteolysis, as
      well as reduced values of Ki. The implications of these factors for the design of
      inhibitors based on this loop motif is discussed.

PMID- 9266474
TI  - C5aR ligand peptide 3D QSAR study performed with an applied linear conformation.
AB  - A 3D quantitative structure-activity relationship study (QSAR) of binding and
      activation of the human C5a receptor by peptide analogs of the C-terminal binding
      domain of C5a anaphylatoxin is reported. Using published C5a analog affinity and
      activity data, this paper seeks to elucidate the pharmacophore for the high
      affinity C-terminal binding domain of the C5a peptide with the molecular modeling
      technique of comparative molecular field analysis (CoMFA). In order to model
      peptides for which there was incomplete conformational data, an arbitrary linear
      conformation was imposed upon the highly flexible C5a analogs. The resulting
      models yield a crossvalidated q2 of 0.889 and 0.787, for receptor-ligand affinity
      and EC50 calcium release activity, respectively, suggesting these models have
      good predictive ability for other test peptides.

PMID- 9266475
TI  - Efficient peptide ladder sequencing by MALDI-TOF mass spectrometry using allyl
      isothiocyanate.
AB  - A new modification of the peptide ladder sequencing technique is described in
      which allyl isothiocyanate (AITC) replaces trifluoroethyl isothiocyanate as the
      volatile amine-modification reagent. AITC is commercially available, readily
      purified, stable up to 80 degrees C and reacts cleanly and rapidly with all amino
      groups of polypeptides. Several model peptides and two side chain-modified
      peptides were sequentially degraded using AITC and the cleavage reagent
      heptafluorobutyric acid (HFBA) up to seven amino acids from the N-terminus.
      Matrix-assisted laser-desorption and ionization coupled with time-of-flight
      (MALDI-TOF) mass spectroscopy of the peptide mixture provided a clear ladder-like
      mass profile with consecutive molecular ions corresponding to each shortened
      peptide at picomole range. The results indicate the general utility of this
      analytical protocol by the use of AITC as the amine-coupling reagent.

PMID- 9266476
TI  - Structure-activity relationships for some elastin-derived peptide
      chemoattractants.
AB  - In an attempt to explore the relationships between conformation of chemotactic
      peptides related to elastin and their biological activity we have studied five
      peptides: VGVAPG, VGVPG, VGAPG, GVAPG and GGVPG in solvents of different
      polarities which may mimic the environmental conditions at the receptor site. CD
      and NMR studies showed that GVAPG has no preference for structured conformations,
      while the other peptides may assume folded conformations in organic solvents. All
      these peptides but GGVPG showed chemotactic activity for monocytes. The
      chemotactic activity of VGVPG, VGAPG and VGVAPG was inhibited by lactose, while
      chemotaxis of peptide GVAPG was insensitive to lactose, suggesting the existence
      of different chemotactic receptors.

PMID- 9266477
TI  - NMR structure of neuromedin C, a neurotransmitter with an amino terminal CuII-,
      NiII-binding (ATCUN) motif.
AB  - The structure of neuromedin C, a 10-residue bombesin-like neuropeptide with the
      sequence Gly-Asn-His-Trp-Ala-Val-Gly-His-Leu-Met-NH2, has been investigated. Like
      human serum albumin, neuromedin C contains the amino-terminal CuII-, NiII-binding
      (ATCUN) motif which has high affinity for CuII and NiII. The solution structure
      of the NiII-peptide complex has been calculated based on 2D ROESY data obtained
      at 25 degrees C, using a hybrid distance geometry-simulated annealing approach.
      Comparison of 1H, 13C and 15N chemical shifts and ROESY data in the presence and
      absence of NiII demonstrates that the metal binds at the N-terminus of the
      peptide, leading to a conformational change. The metal complex adopts a
      conformation comprising two connected turns including residues 1Gly to 3His and
      5Ala to 8His. The first turn corresponds to the NiII coordination ligands in a
      square planar conformation, and the second reflects the interaction between 4Trp
      and 8His. The results may have important physiological implications in the
      phenomenon of neurotransmission.

PMID- 9266478
TI  - Evaluation of laminin peptide fragments labeled with indium-111 for the potential
      imaging of malignant tumors.
AB  - The laminin peptide fragments GYIGSR-NH2 and CDPGYIGSR-NH2 are known to bind to a
      67-kDa laminin receptor. This receptors is understood to be expressed at higher
      than normal levels in malignant tumor cells, particularly those of breast and
      colon carcinomas. Peptides DTPA-GYIGSR-NH2 (1), DTPA-(GYIGSR-NH2)2 (2), DTPA
      CDPGYIGSR-NH2 (3), DTPA-(CDPGYIGSR-NH2)2 (4), and negative control DTPA-GAGAGA
      NH2 (5) were prepared by solid-phase peptide synthesis. All five DTPA-conjugated
      peptides were subsequently radiolabeled with 111In and their tissue distribution
      evaluated in mice bearing C3H tumors. 111In-3 and 111In-4 showed the highest
      specific tumor localization. These preliminary data support further study of
      radiolabeled petide fragments for the potential detection of malignant tumors of
      the breast and other organs.

PMID- 9266479
TI  - Inhibition of homotypic adhesion of T-cells: secondary structure of an ICAM-1
      derived cyclic peptide.
AB  - The objective of this study was to elucidate the solution conformation of cyclo
      (1,12) Pen1-Pro2-Ser3-Lys4-Val5-Ile6-Leu7-Pro8-Ar g9-Gly10-Gly11-Cys12 (1)
      derived from the intercellular adhesion molecule-1 (ICAM-1). Cyclic peptide 1
      inhibits homotypic adhesion of T-cells (Molt-3) mediated by ICAM-1 and the
      leukocyte function-associated antigen-1 (LFA-1) on the surface of T-cells. Cyclic
      peptide 1 is more potent than is the linear peptide Pen1-Pro2-Ser3-Lys4-Val5-Ile6
      Leu7-Pro8-Ar g9-Gly10-Gly11-Cys12 (2) in inhibiting homotypic adhesion. The
      difference in biological activity of peptides 1 and 2 may be due to the more
      stable conformation of cyclic peptide 1 compared to linear peptide 2 or because
      cyclization prevents the peptide from adopting non-productive conformation.
      Therefore, conformational studies of cyclic peptide 1 will give a better
      understanding of its biological active conformation. The conformational studies
      of cyclic peptide 1 were done by NMR, CD and molecular dynamics simulations. NMR
      studies indicated that the major conformation of cyclic peptide 1 contained trans
      configuration at both X-Pro peptide bonds. Type I beta-turns at Lys4-Val5-Ile6
      Leu7 and Leu7-Pro8-Arg9-Gly10 were found in cyclic peptide 1. The C- and N
      terminal regions of this peptide were stabilized by antiparallel beta-sheet-like
      structure with the presence of intramolecular hydrogen bonds. The overall
      structure of this peptide exposed the hydrophobic side chains on one face of the
      molecule and the hydrophilic side chains on the other.

PMID- 9266480
TI  - Pegylated peptides. V. Carboxy-terminal PEGylated analogs of growth hormone
      releasing factor (GRF) display enhanced duration of biological activity in vivo.
AB  - In the present study, human growth hormone-releasing factor (hGRF) and analogs
      were successfully pegylated at the carboxy-terminus using a novel solid- and
      solution-phase strategy. Following synthesis, these pegylated hGRF analogs were
      evaluated for in vitro and in vivo biological activity. Specifically, hGRF (1-29)
      NH2, [Ala15]-hGRF (1-29)-NH2, [desNH2Tyr1, D-Ala2, Ala15]-hGRF(1-29)-NH2 and
      [His1, Val2, Gln8, Ala15, Leu27]-hGRF(1-32)-OH were each C-terminally extended
      using a Gly-Gly-Cys-NH2 spacer (previously demonstrated not to alter intrinsic
      biological activity), and then monopegylated via coupling to an activated
      dithiopyridyl-PEG reagent. PEG moieties of 750, 2000, 5000 or 10,000 molecular
      weight (MW) were examined to determine the effect of polymer weight on activity.
      Initial biological evaluations in vitro revealed that all C-terminally pegylated
      hGRF analogs retained high growth hormone (GH)-releasing potencies, regardless of
      the MW of PEG polymer employed. Two of these pegylated hGRF analogs, [desNH2Tyr1,
      D-Ala2, Ala15]-hGRF (1-29)-Gly-Gly-Cys(NH2)-S-Nle-PEG5000 and [His1, Val2, Gln8,
      Ala15, Leu27]-hGRF(1-32)-Gly-Cys(NH2)-S-Nle-PEG5000, were subsequently evaluated
      in both pig and mouse models and found to be highly potent (in vivo potency range
      = 12-55-fold that of native hGRF). Relative to their non-pegylated counterparts,
      these two pegylated hGRF analogs exhibited enhanced duration of activity.

PMID- 9266481
TI  - HIV-1 protease inhibitors containing a novel C2 symmetrical hydroxyalkylgem
      diamino core structure.
AB  - Two series of peptidomimetics containing a novel C2 symmetrical hydroxyalkylgem
      diamino core structure were prepared, from amino acid starting materials, and
      evaluated as inhibitors of HIV-1 protease (HIV-1 Pr). 1,1-Diamino-3
      hydroxypropane (gHse) derivatives showed weak inhibitory potency (IC50 > 10
      microM). In the 1,1-diamino-2-hydroxyethane (gSer) series, a compound containing
      P1/P1' benzyl and P2/P2'Fmoc substituents, displayed a significant HIV-1 Pr
      inhibition (IC50 = 440 nM).

PMID- 9266482
TI  - Characterization of a new family of toxin-like peptides from the venom of the
      scorpion Leiurus quinquestriatus hebraeus. 1H-NMR structure of leiuropeptide II.
AB  - To extend our knowledge about the structural features of short scorpion toxins,
      the ion-exchange fractions obtained from Leiurus quinquestriatus hebraeus venom
      were investigated by plasma desorption mass spectrometry in order to select low
      molecular mass polypeptides. Three toxin-like peptides with molecular mass close
      to 3 kDa, named leiuropeptides I, II and III, were purified and found devoid of
      any significant toxicity against mammals and insects. Their amino acid sequences
      revealed a cysteine pattern analogous to that of short-chain scorpion toxins. The
      solution structure of leiuropeptide II was determined by 2D 1H-NMR spectroscopy
      and indicated the presence of a helix accommodating a proline, connected to a two
      standard beta-sheet by three disulfide bonds. The overall fold of leiuropeptide
      II is found to be similar to that of leiurotoxin I, a 31-residue toxin present in
      the same scorpion venom which acts on K+ channels. In order to rationalize the
      absence of toxicity, the electrostatic potential of leiuropeptide II was compared
      to that of leiurotoxin I. The peptide is characterized by a large negative zone
      around Glu4, Asp5 and Asp8 residues, beginning in the neighbourhood of the beta
      turn and extending along the helix. In the same area, leiurotoxin I exhibits a
      positive surface, around Arg6 and Arg13 basic residues, which are essential for
      its receptor affinity.

PMID- 9266483
TI  - Aza-peptides. II. X-ray structures of aza-alanine and aza-asparagine-containing
      peptides.
AB  - In order to determine the structural consequences of the N alpha/C alpha H
      exchange in aza-peptides, we have solved the crystal molecular structures of some
      derivatives containing the aza-analogue of asparagine [Z-AzAsn(Me)-NMe2 (1), Z
      AzAsn(Me)-Pro-NHiPr (2) and Piv-Pro-AzAsn(Me)-NHiPr (5)], aspartic acid [Z
      AzAsp(OEt)-Pro-NHiPr (3) and alanine (Boc-AzAla-Pro-NHiPr (4)], by using X-ray
      diffraction. They reveal that the alpha-nitrogen accommodates a pyramidal (1-4)
      or planar (5) structure depending on the sequence. When pyramidal, the alpha
      nitrogen assumes the R (D-like) chirality. All of the derivatives but 1 adopt
      either a beta 1-folded (2-4) or beta n-folded (5) structure in which the
      (AzAsn)N3H bond is intramolecularly hydrogen-bonded to the alpha-nitrogen.

PMID- 9266484
TI  - Membrane interaction of synthetic peptides related to the putative fusogenic
      region of PH-30 alpha, a protein in sperm-egg fusion.
AB  - In order to investigate the relationship between structure and function of a
      putative fusogenic region of PH-30a, a protein active in sperm-egg fusion, two
      peptides, SFP22 and SFP23, whose sequences correspond to the residues 90-111 and
      89-111 of PH-30 alpha, respectively, were chemically synthesized. An analog of
      SFP23, SFP23AA, which has an Ala-Ala sequence instead of the Pro-Pro sequence in
      SFP23, was also prepared. The CD study indicated that SFP22 and SFP23 mainly took
      a beta-structure in the presence of DPPC and DPPC/DPPG (3/1) vesicles, while
      SFP23AA showed an alpha-helical pattern though the alpha-helical content
      calculated was low (25-30%). alpha-Helical CD curve was observed for these
      peptides in trifluoroethanol. The membrane-perturbing activity of SFP22 and SFP23
      was weaker than that of SFP23AA. On the other hand, the membrane-fusogenic
      activity of SFP22 and SFP23 to acidic phospholipid bilayers was much stronger
      than that of SFP23AA. All the peptides caused very weak cell lysis. These results
      are consistent with the reported speculation [Blobel, C. P. et al. (1992), Nature
      (London) 356, 248-252] that residues 90-111 of PH-30 alpha may be the fusogenic
      region and suggest that the Pro-Pro sequence is one of the important factors for
      holding the active secondary structure of the fusogenic region of PH-30 alpha in
      membranes.

PMID- 9266485
TI  - Preparation and properties of N alpha-Bpoc-amino acid pentafluorophenyl esters.
AB  - The preparation and properties are reported of several N alpha-Bpoc -amino acid
      pentafluorophenyl esters, including those bearing tert-butyl-, allyl- and trityl
      based protecting groups. These derivatives have been used in the solid-phase
      peptide synthesis of several short peptides.

PMID- 9266486
TI  - Complex formation between a formyl peptide and 24p3 protein with a blocked N
      terminus of pyroglutamate.
AB  - We have purified 24p3 protein from mouse uterine fluid (Biochem. J. 316, 545-550,
      1996). It is a 25.8-kDa glycoprotein with a N-blocked terminus. This work
      demonstrated the N-blocked residue to be pyroglutamate, supporting the post
      translational cleavage site at Ala-Gln in the precursor protein to generate a
      putative protein of 180 amino acid residues. Consequently, the two cysteines,
      Cys78 and Cys177, and the two tryptophans, Trp31 and Trp81, are assigned along
      the polypeptide chain. No free thiol group was detected in the protein. The
      presence of formyl-Met-Leu-Phe in the protein solution causes a considerable
      decrease in the protein fluorescence due to Trp31 and Trp81. Analysis of the
      fluorescence data supports the idea that the protein can be complexed with the
      formyl peptide. The association constant for the complex formation is (4.8 +/-
      0.29) x 10(5) M-1 at pH 7.4.

PMID- 9266487
TI  - In vitro reactivity of the antineoplastic drug carmustin and acrolein with model
      peptides.
AB  - The in vitro interaction of the antineoplastic drug 1,3-bis-(2-chloroethyl)-1
      nitrosourea (BCNU) and acrolein with model peptides has been investigated in
      order to provide a detailed description of their electrophilic reactivity towards
      biological macromolecules. Following incubation with these substances, the
      modified species were separated by HPLC and identified by fast atom bombardment
      mass spectrometry, whereas the reactive amino acids within the peptide structure
      were assigned by tandem mass spectrometry. Incubation with BCNU led essentially
      to the formation of an N-terminal carbamoyl derivative that slowly decomposed to
      form three isomeric structures and a very minor ethylated adduct. Alkylation with
      acrolein gave rise to a mixture of different adducts due to the reaction of both
      the double bond and the carbonyl group. Two species containing intramolecular
      cross-links were also observed. These results constitute the prerequisite for in
      vitro and in vivo studies on the modification of haemoglobin in patients
      following treatment with antineoplastic drugs.

PMID- 9266488
TI  - Histidine-rich human salivary peptides are inhibitors of proprotein convertases
      furin and PC7 but act as substrates for PC1.
AB  - A 32 amino acid peptide called histatin-3 (H3; 22% His) and its N-terminal 24
      amino acid fragment histatin-5 (H5, 33% His), are found in human saliva and
      possess powerful antimicrobial properties. These His-rich peptides have been
      synthesized by Fmoc-based solid-phase chemistry. Their sequences are:
      DSHAKRHHGYKRKFHEKHHSHRGYRSNYLYDN (H3) and DSHAKRHHGYKRKFHEKHHSHRGY (H5). In
      addition, we also prepared two H5 and one H3 mutants. The H5 mutants were: DH5
      (all amino acids in D configuration) and H5F (where all His are replaced by Phe
      at positions 3, 7, 8, 15, 18, 19, 21). The 9-24 segment of H3 with all the His at
      positions 15,18,19,21 replaced by Tyr was also prepared (delta 1-8 H3Y). The
      behavior of these five peptides was examined with three proprotein convertases
      (PC's) which possess cleavage specificity directed towards single and pairs of
      basic residues. These were: human (h)PC1, an endocrine and neural convertase,
      hfurin and rat (r)PC7, two widely expressed enzymes. All are serine endoproteases
      belonging to the kexin/subtilisin family. Our in vitro study revealed that H3
      behaves as a substrate for PC1, being cleaved by this endoprotease primarily at a
      site carboxy terminal to the single Arg25 residue (HRGYR decrease SN). On
      prolonged incubation some minor cleavage was also observed C-terminal to the
      first LysArg6 pairs of basic amino acids namely at: HAKR decrease HH, which
      contains a P4 as well as P'1 and P'2 His residues. The second potential site
      YKRK12-FH which does not have a P4 basic residues is not cleaved, even upon
      incubation with excess protease. PC1 only poorly cleaves H5 at the same site
      mentioned above for H3, i.e., at HAKR decrease HH. As expected, neither the D
      amino acid analogue (DH5), nor the Phe and Tyr mutant analogues of the long and
      short histatins, respectively, are cleaved at all. In contrast to the above
      findings for hPC1, the convertase hfurin did not cleave any of the five synthetic
      peptides. Instead, H3 and H5 were found to be moderately potent inhibitors of the
      furin-mediated cleavage of the pentapeptide pGlu-Arg-Thr-Lys-Arg-MCA fluorogenic
      substrate. This inhibition was reversible and competitive, with an estimated
      inhibition constant Ki of 1.98 microM for H3 and 2.98 microM for H5. The other
      analogs exhibited only a moderate to weak inhibition of furin, suggesting that
      substitution of all His by aromatic residues (Phe or Tyr) drastically reduces
      their inhibitory potency. When tested against rPC7, H3 exhibited almost identical
      inhibition profile with a measured Ki of 2.4 microM. The partial sequence
      identity of H3 to the inhibitory pro-peptide of furin and PC7 provides a
      rationale for our observation.

PMID- 9266489
TI  - Hydrogen bonding in peptide helices. Analysis of two independent helices in the
      crystal structure of a peptide Boc-Val-Ala-Leu-Aib-Val-Ala-Phe-OMe.
AB  - The crystal structure determination of the heptapeptide Boc-Val-Ala-Leu-Aib-Val
      Ala-Phe-OMe reveals two peptide helices in the asymmetric unit. Crystal
      parameters are: space group P2(1), a = 10.356(2) A, b = 19.488(5) A, c =
      23.756(6) A, beta = 102.25(2) degrees, V = 4685.4 A3, Z = 4 and R = 5.7% for 7615
      reflections [I > 3 sigma (I)]. Both molecules adopt largely alpha-helical
      conformations with variations at the C-terminus. Helix type is determined by
      analysing both 4-->1 and 5-->1 hydrogen-bond interactions and comparison with the
      results of analysis of protein structures. The presence of two 4-->1 hydrogen
      bond interactions, besides four 5-->1 interactions in both the conformations
      provides an opportunity to characterize bifurcated hydrogen bonds at high
      resolution. Comparison of the two helical conformations with related peptide
      structures suggests that distortions at the C-terminus are more facile than at
      the N-terminus.

PMID- 9266490
TI  - Identification of new autolytic sites of recombinant truncated mature human
      fibroblast stromelysin by mass spectrometry.
AB  - Stromelysin has been proposed to play a major role in the pathologic degradation
      of diseased cartilage of osteoarthritis and rheumatoid arthritis patients. A
      truncated, recombinant form of this enzyme, with the sequence Phe83 to Thr260
      (mSL-t), has been expressed and purified from E. coli to investigate its
      biochemical and biophysical properties, and to develop inhibitors for arthritis
      treatment. LC/ESI-MS technique was utilized for the characterization of mSL-t.
      The mass spectra of mSL-t showed the presence of a number of different protein
      components in addition to the full-length mSL-t form. We have demonstrated that
      protein degradation arose from autolysis. Molecular weights determined by LC/ESI
      MS of these autolysis products allowed for the identification of new autolytic
      sites in mSL-t. Furthermore, two strategies were undertaken to prepare mSL-t free
      of degradation products. These include preparation of a mutant form of the enzyme
      in which Arg163 was substituted for Leu163 and purification of mSL-t using
      affinity chromatography. The LC/ESI-MS data of the mutant protein confirmed the
      Leu to Arg mutation. The affinity-purified material showed only one LC peak in
      the LC/MS chromatograms, and the mass spectrum of the peak identified only the
      intact protein, demonstrating that the full-length protein has been successfully
      separated from the autodegradation products and further autolysis of the enzyme
      has been prevented.

PMID- 9266491
TI  - Preparation of a multiple antigen glycopeptide (MAG) carrying the Tn antigen. A
      possible approach to a synthetic carbohydrate vaccine.
AB  - The glycosidic tumor-associated Tn antigen was conjugated to a lysine backbone
      containing a helper T-cell epitope in order to activate immune responses specific
      for some types of carcinomas. As opposed to traditional protein conjugates, this
      multiple antigen glycopeptide (MAG) offers the advantages of the lack of
      immunogenicity of the polylysine core and of accurate chemical definition. The
      MAG construction was assembled by conventional solid-phase peptide synthesis. The
      analysis of its antigenicity demonstrated that the Tn antigen on the MAG is
      recognized by Tn-specific monoclonal antibodies.

PMID- 9266492
TI  - Furcation involvement: comparison of dental radiographs and HR-CT-slices in human
      specimens.
AB  - In this in vitro study we compared dental radiographs and high resolution
      computed tomography (HR-CT) regarding identification and classification of the
      degree of horizontal and vertical furcation involvement. After removal of the
      soft tissue and metallic restorations of 18 dentate upper and lower jaws in the
      interradicular furcation region of 28 molars, bony defects of different
      dimensions were experimentally produced. The specimens were examined
      radiographically with standardized dental radiographs and 1.0 mm thick contiguous
      axial CT-scans. After identification of molars with artificial furcation
      involvement in the dental radiographs and axial CT-scans, the horizontal and
      vertical grades of furcation involvement were classified. Radiological
      identification and classification were compared with the macroscopic findings in
      the specimens. For quantitative histological-radiological comparison,
      corresponding microsections were prepared in the same plane as the axial CT
      scans. In the dental radiographs the artificial furcation involvement in 6 of 28
      (21%) molars was identified. In contrast, all 28 molars with involved furcations
      (100%) were identified in the axial CT-scans. The horizontal and vertical grades
      of furcation involvement were classified in the same way as the macroscopic
      findings, permitting comparison of histological sections and axial CT-scans. The
      HR-CT technique offers 3-dimensional assessment of the interradicular bone
      morphology in furcation involvement without overlying structures. The
      periradicular alveolar bone can be assessed on all sides of the roots. HR-CT
      scanning thus permits a high identification rate and classification of molars
      with involved furcations.

PMID- 9266493
TI  - Collagen implants do not preserve periodontal ligament homeostasis in periodontal
      wounds.
AB  - An improved understanding of the differentiation of periodontal ligament cells
      could facilitate the development of new treatment approaches for overcoming the
      loss of specialized cell types caused by periodontitis. To study healing of
      wounded periodontal tissues and the differentiation of mineralizing connective
      tissue cells in periodontal ligament, we have examined the influence of wound
      size and collagen implantation on the regeneration of periodontium and on
      immunohistochemical staining for osteopontin and bone sialoprotein. Four groups
      of Wistar rats were wounded by drilling through the alveolar bone and by
      extirpation of the periodontal ligament. Wounds were 0.6 or 1.8 mm in diameter
      and defects were either implanted with collagen gels or were treated without
      implants. Rats were killed at 1 wk or 2 months after wounding and tissue sections
      were stained with monoclonal antibodies against rat osteopontin and bone
      sialoprotein. Collagen implants strongly increased staining for osteopontin and
      bone sialoprotein in defects at 1 wk. By 2 months alveolar bone healed completely
      regardless of the wound size but in large defects, periodontal ligament width was
      significantly reduced with or without implants. In large wounds at 2 months,
      collagen implants inhibited bone regeneration and there was stronger staining for
      osteopontin and bone sialoprotein in the bone replacing the implant, indicating
      that collagen prolonged bone remodelling. We conclude that implantation of
      exogenous collagen affects alveolar bone healing but does not preserve the width
      of the regenerated periodontal ligament. Therefore collagen does not appear to
      contribute to homeostasis in the periodontium following wounding.

PMID- 9266494
TI  - Components of a randomized clinical trial.
AB  - The purpose of this paper is to discuss a number of components associated with
      the design, development and conduct of a randomized clinical trial (RCT). In a
      RCT, a patient is entered into a protocol in which therapy is randomly assigned.
      Thus, neither the patient nor the care provider have active roles in deciding
      treatment. The elements of informed consent were developed to ensure that the
      patient's interests are protected. The informed consent document serves as the
      cornerstone of a clinical study by introducing patients to the research protocol,
      informing them of their role as participants in the study, and educating them of
      their rights. Questions regarding ethics arise during all phases of a study. A
      study designed with insufficient sample size will provide inconclusive data, thus
      making participation in the study of limited to no value. Conversely, having
      patients enrolled in a RCT after data has proved superiority of an arm of the
      study postpones beneficial therapy for patients and society. Other ethical
      conflicts arise when subjects are recruited for clinical trials. Special care
      must be taken to avoid coercion in protected populations such as students,
      employees, the mentally challenged, and the indigent. Careful planning with
      adequate attention to consent from development can minimize problems and optimize
      patient care and research integrity.

PMID- 9266495
TI  - Loss of Fc gamma receptor and impaired phagocytosis of polymorphonuclear
      leukocytes in gingival crevicular fluid.
AB  - Immunoglobulin G type II and III receptors (Fc gamma RII and Fc gamma RIII) are
      essential for polymorphonuclear leukocytic (PMNs) phagocytosis. Our previous
      study demonstrated a downregulation of Fc gamma RIII on PMNs in gingival
      crevicular fluid (GCF). To determine whether this receptor downregulation may
      contribute to the periodontal host defence borne by PMNs, we examined the
      correlation between Fc gamma RII and Fc gamma RIII expressions and the phagocytic
      capacity of GCF-PMNs. In order to verify at which level of cellular events the
      loss of Fc gamma R occurs, we quantified mRNA levels to assess a de novo
      synthesis of these receptors. GCF was collected from 21 patients with adult
      periodontitis by gingival crevicular washing. Autologous peripheral blood (PB)
      PMNs served as control. Surface expressions of Fc gamma Rs and phagocytic
      capacity via Fc gamma Rs were analysed by flow cytometry. The difference in Fc
      gamma R mRNA levels between GCF- and PB-PMNs was assessed by reverse
      transcription polymerase chain reaction (RT-PCR). The amplified products were
      visualized by agarose gel electrophoresis and the endproduct yields were
      quantified by computerized image-analysis. Both Fc gamma RII and Fc gamma RIII
      expressions and phagocytic capacity on GCF-PMNs were significantly lower than
      those on PB-PMNs (p < 0.001). The downregulation of Fc gamma Rs on GCF-PMNs
      significantly correlated with the phagocytic capacity (r = 0.66 for Fc gamma
      RIII, p < 0.01; r = 0.50 for Fc gamma RII, p < 0.05). The mRNA level of Fc gamma
      RIII of GCF-PMNs was significantly lower than that of PB-PMNs (p < 0.05). Thus,
      GCF-PMNs are characterized by the decreased surface expressions and mRNA levels
      of Fc gamma Rs, and the impaired phagocytosis.

PMID- 9266496
TI  - Prostaglandin E2 and interleukin-1 concentrations in nicotine-exposed oral
      keratinocyte cultures.
AB  - Oral keratinocytes are the first cells in contact with tobacco components and are
      capable of producing various inflammatory mediators, including PGE2 and IL-1. The
      purpose of this study was to examine PGE2 and IL-1 concentrations in nicotine
      exposed oral keratinocyte cultures. Gingival keratinocyte cultures were
      established from healthy gingival tissues obtained from 7 subjects. Cultures were
      divided into 4 groups exposed to serum free medium (control), 0.1 microM, 10
      microM or 1 mM nicotine for 4, 24 or 48 h. Using enzyme-linked immunosorbent
      assays, PGE2 and IL-1 alpha were quantified in culture supernatants; IL-1 alpha
      and beta were also measured in lysed cells. A repeated measures analysis of
      variance was used to identify significant differences over time and treatment.
      Nicotine exposure did not significantly alter PGE2 levels at any given time
      period; however, PGE2 quantities declined significantly (p = 0.0001) over time.
      At both 24 and 48 h, IL-1 alpha concentrations in lysates from 1 mM nicotine
      exposed cells were significantly (p < 0.01) greater than those for all other
      treatments. Interleukin-1 alpha quantities also declined significantly (p =
      0.037) over time in the cultures. Interleukin-1 beta concentrations were
      elevated, albeit not significantly, in the 1 mM treated cells at 24 and 48 h.
      Cell viability, mass and counts were not affected by nicotine treatment; these
      parameters increased significantly (p < 0.005) over time. In summary, nicotine
      treatment significantly increased IL-1 alpha concentrations in cultured
      keratinocytes; however, PGE2 synthesis was not altered. Elevated IL-1 production
      by keratinocytes may have implications in tobacco-induced lesions, given the
      central role IL-1 plays in tissue response to injury.

PMID- 9266497
TI  - Lipoproteins of Treponema denticola: their effect on human polymorphonuclear
      neutrophils.
AB  - The presence of lipoproteins and lipooligosaccharides in Treponema denticola, an
      oral spirochaete associated with periodontal diseases, was investigated. T.
      denticola ATCC 35404 and the clinical isolate GM-1 were metabolically labeled
      with [3H]-cis-9-octadecenoic acid and extracted with the non-ionic detergent
      Triton X-114. The extract was phase separated, precipitated with acetone and
      delipidated to remove non-covalently bound lipid (dLPP). In T. denticola ATCC
      35404, sodium dodecyl sulfate polyacrylamide electrophoretic separation followed
      by autoradiography showed [3H]-cis-9-octadecenoic acid incorporation in bands
      with apparent molecular masses of 14, 20, 26, 31, 38, 72 and 85 kDa and a broad
      band running from 113 kDa to the top of the gel. This last band resolved into a
      53 kDa [3H]-cis-9-octadecenoic acid band upon heating for 10 min, at 100 degrees
      C. The structural relationship of the outer sheath major oligomeric polypeptide
      of strain ATCC 35404 and the 53 kDa protein was demonstrated immunologically.
      Antibodies against the 113 kDa component of the oligomer cross-reacted with the
      53 kDa protein. Proteinase K degraded the [3H]-cis-9-octadecenoic acid bands with
      the exception of the 14 kDa. The 14 kDa was also the major [3H]-fatty acid
      labeled compound found in the water phase following phenol-water extraction of
      whole T. denticola ATCC 35404 cells. This compound was purified from the water
      phase by gel filtration followed by hydrophobic chromatography. Chemical analysis
      showed that hexadecanoic acid was the predominant fatty acid bound to T.
      denticola lipoproteins. In the GM-1 strain [3H]-cis-9-octadecenoic acid
      incorporation was observed in the 116 kDa and 14 kDa bands. dLPP from strain ATCC
      35404 caused an enhanced (0.8-8 micrograms/ml) luminol dependent
      chemiluminiscence (LDCL) effect in human polymorphonuclear neutrophils (PMN)
      which could be related to protein concentration. The addition of dLPP to PMN
      together with FMLP at submaximal concentration (1 microM) resulted in a
      synergistic activation of LDCL. At 21 micrograms/ml, dLPP also induced lysozyme
      release by the PMN at approximately 30% of the release induced by the chemotactic
      peptide at 1 microM. In addition, dLPP (21 micrograms/ml) increased additively
      the release of lysozyme caused by 1 microM FMLP. The release of beta
      glucuronidase was not affected. The modulation of neutrophil activity was
      abolished by preincubation of dLPP with proteinase K. The purified 14 kDa had no
      effect on either LDCL or exocytosis of lysosomal enzymes of PMN. These data
      strongly suggest that T. denticola possesses several lipoproteins including outer
      sheath major oligomeric polypeptides (113-234 kDa) and a lipooligosaccharide of
      molecular mass of 14 kDa. In addition, an enriched lipoprotein fraction from this
      oral spirochaete modulates oxygen dependent and independent mechanisms for
      controlling microorganisms by human PMN.

PMID- 9266498
TI  - In situ hybridization study on tissue inhibitors of metalloproteinases (TIMPs)
      mRNA-expressing cells in human inflamed gingival tissue.
AB  - This study presents the exact cell types and localization of tissue inhibitors of
      metalloproteinases (TIMPs) production sites in periodontal diseased gingiva by
      means of in situ hybridization. Gingival tissue specimens were fixed, embedded
      and hybridized in situ with specific digoxigenin-labeled cRNA probes (386 and 496
      bp). TIMP-1 and -2 mRNAs were expressed on macrophages, mononuclear cells,
      capillary endothelial cells and some fibroblasts throughout the gingival tissue.
      In periodontitis, TIMP-1 and -2 mRNA-expressing cells showed significantly
      different localization. TIMP-1 mRNA was broadly observed in the gingival
      connective tissue while TIMP-2 mRNA was predominantly expressed in the connective
      tissue adjacent to the pocket epithelium (p < 0.01). Fewer TIMPs mRNA were
      observed in minimal gingivitis than in periodontitis, especially in the middle
      zone of gingival tissue. Thus, TIMP-1 and TIMP-2 mRNA was detected differentially
      and site-specifically in periodontal diseased gingival tissue.

PMID- 9266499
TI  - Effects of metronidazole on Porphyromonas gingivalis biofilms.
AB  - Subgingival bacteria exist within a biofilm consisting of cells and extracellular
      matrix which may afford organisms protection from both antibiotics and components
      of the host immune system. MIC values for planktonic Porphyromonas gingivalis
      treated with metronidazole were compared with those obtained for the same strain
      in biofilms associated with hydroxyapatite (HA) surfaces. The treated biofilms
      were examined for growth and studied by scanning electron microscopy. A broth
      assay resulted in an MIC of 0.125 microgram/ml for metronidazole against P.
      gingivalis, P. gingivalis biofilms exhibited growth after treatment with 20
      micrograms/ml metronidazole, which was 160 times the MIC for planktonic
      organisms. The results of this study indicate that biofilm-associated P.
      gingivalis may be resistant to metronidazole at concentrations which are usually
      attained by systemic administration.

PMID- 9266500
TI  - The diversity of coenzyme Q function.
AB  - Coenzyme Q is uniquely designed as an electron and proton carrier within the
      lipid phase of membranes. It now appears that this unique chemistry has diverse
      application to important functions in all cellular membranes. The first function
      of coenzyme Q was defined in the energy transduction process in mitochondria. New
      studies show that the presence of coenzyme Q in other cellular membranes has
      dynamic rather than passive significance. Coenzyme Q functions in the plasma
      membrane electron transport involved in activation of signalling protein kinases
      related to gene activation for cellular proliferation. Furthermore, the
      antioxidant potential of the reduced coenzyme Q is now taken on a new
      significance in the evidence that the reduced quinone can act to maintain
      tocopherol in the reduced state in membranes and ascorbate reduced both inside
      and outside the cell.

PMID- 9266501
TI  - Role of cytochrome b5 reductase on the antioxidant function of coenzyme Q in the
      plasma membrane.
AB  - Cytochrome b5 reductase purified from liver plasma membrane reduces coenzyme Q
      (CoQ) in reconstituted liposomes in the absence of cytochrome b5. Both CoQ and
      its reductase are responsible for the reduction of the ascorbate free radical at
      the cell surface. Thus, NADH-CoQ reductase represents a partial reaction of NADH
      AFR reductase in the plasma membrane. Cytochrome b5 reductase maintains CoQ and
      ascorbate in their reduced state to support antioxidations. Reduced CoQ prevents
      lipid peroxidation in liposomes and plasma membranes. Also, oxidized CoQ can
      prevent lipid peroxidations in the presence of cytochrome b5 reductase and NADH.
      Addition of CoQ to intact cells prevents serum withdrawal-induced lipid
      peroxidation and apoptosis. The prevention of apoptosis by CoQ is independent of
      the bcl-2 protein content in the cell. Antioxidants that act at the plasma
      membrane as CoQ and ascorbate would represent a first barrier to protect lipids
      from oxidative stress and subsequent apoptosis. Cytochrome b5 reductase is then
      an enzyme leading this function at the plasma membrane. These data support the
      idea that when the plasma membrane barrier fails, bcl-2 protein would be required
      to prevent cell death.

PMID- 9266502
TI  - The two-electron quinone reductase DT-diaphorase generates and maintains the
      antioxidant (reduced) form of coenzyme Q in membranes.
AB  - The experiments reported here were undertaken to test the hypothesis that the
      antioxidative, reduced form of hydrophobic phase coenzyme Q (CoQ) may be
      generated and maintained by the two-electron quinone reductase, DT-diaphorase
      [NAD(P)H:(quinone-acceptor) oxidoreductase, EC 1.6.99.2] by catalyzing formation
      of the hydroquinone form of CoQ. This enzyme was isolated and purified from rat
      liver cytosol and its reduction of several CoQ homologs incorporated into large
      unilamellar vesicles (LUVETs) was demonstrated. The addition of NADH and DT
      diaphorase to LUVETs and to multilamellar vesicles (MLVs) containing CoQ
      homologs, including CoQ9 and CoQ10, resulted in essentially complete reduction of
      the CoQ. Incorporation of either CoQ9H2 or CoQ10H2 and the lipophylic radical
      generator 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN) into MLVs in the presence
      of DT-diaphorase and NADH maintained the reduced state of CoQ and inhibited lipid
      peroxidation. The reaction between DT-diaphorase and CoQ was also demonstrated in
      isolated rat liver hepatocytes in which incorporation of CoQ10 provided
      protection from adriamycin (adr)-induced mitochondrial membrane damage. The role
      of DT-diaphorase in the antioxidant activity of CoQ was demonstrated by the co
      incorporation of dicoumarol (dic), a potent inhibitor of DT-diaphorase, resulting
      in a loss of protection by incorporated CoQ10. These results support the
      antioxidant function of DT-diaphorase in both artificial and natural membrane
      systems by acting as a two-electron CoQ reductase which forms and maintains CoQ
      in the reduced state.

PMID- 9266503
TI  - Coenzyme Q deficiency in mitochondria: kinetic saturation versus physical
      saturation.
AB  - The coenzyme Q (CoQ) concentration in the inner membrane of beef heart
      mitochondria is not kinetically saturating for NADH oxidation inasmuch as the
      K(m) of NADH oxidation for endogenous CoQ10 is in the mM range in membrane
      lipids. Using CoQ1 as an electron acceptor from complex I, we have found
      additional evidence that the high Km of NADH oxidase for CoQ is not an artifact
      due to the use of organic solvents in reconstitution studies. We have also
      obtained experimental evidence that CoQ concentration may be rendered more rate
      limiting for NADH oxidation either by a decrease of CoQ content (as in liver
      regeneration or under an acute oxidative stress), or by a possible increase of
      the Km for CoQ, as in some mitochondrial diseases and ageing. The possibility of
      enhancing the rate of NADH oxidation by CoQ therapy is hindered by the fact that
      the CoQ concentration in mitochondria appears to be regulated by its mixability
      with the membrane phospholipids. Nevertheless CoQ10 incorporated into heart
      submitochondrial particles by sonication enhances NADH oxidation (but not
      succinate oxidation) up to twofold. Nontoxic CoQ homologs and analogs having
      shorter side-chains with respect to CoQ10 can be incorporated in the
      mitochondrial membrane without sonication, supporting an enhancement of NADH
      oxidation rate above 'physiological' values. It is worth investigating whether
      this approach can have a therapeutical value in vivo in mitochondrial
      bioenergetic disorders.

PMID- 9266504
TI  - Endogenous and exogenous regulation of redox-properties of coenzyme Q.
AB  - Ubiquinol (QH2, reduced coenzyme Q) is increasingly reported to exert antioxidant
      functions besides its implication in mitochondrial energy metabolism. On the
      other hand ubisemiquinones (SQ-.) of the respiratory chain are considered to
      account for the production of superoxide radicals as a byproduct of cellular
      respiration. Since the formation of potentially prooxidative ubisemiquinones can
      be expected to result from the antioxidant activity of ubiquinol, the evaluation
      whether or not QH2 exerts antioxidant activities depends on the fate of
      antioxidant-derived metabolites and the existence of a natural recycling system
      for oxidized QH2. We have recently shown that SQ increasingly undergo
      autoxidation when approaching the external more polar phase of the membrane. In
      contrast to mitochondria where the QH2/ SQ-./Q pools are dynamically kept in
      relatively stable relationships the fate of semi and fully oxidized QH2 is not at
      all clear in LDL particles where QH2 is suggested to exert important antioxidant
      functions. Therefore, the antioxidant-derived metabolites of QH2 in liposomes
      following lipid peroxidation were studied with respect to their localization in
      the bilayer and the possibility to recycle oxidized QH2 via dihydrolipoic acid
      (DHLA). The results revealed a considerable fraction of QH2 existing in the outer
      membrane section where protons from the aqueous phase have access to allow
      autoxidation. DHLA was found to recycle oxidized QH2 although due to slow
      partition equilibration the reduction velocity appears to be not sufficient for
      therapeutic application.

PMID- 9266505
TI  - The redox state of coenzyme Q10 in mitochondrial respiratory chain and oxygen
      derived free radical generation in cardiac cells.
AB  - The aim of this study was to relate changes in the redox state of mitocondrial
      electron carriers to the 'burst' of oxyradicals in postischemic myocardium. The
      free radical EPR signals of control and re-oxygenated rat hearts were mainly due
      to coenzyme Q10, the line width was 0.81 +/- 0.02 mT, and the intensities (1.58
      +/- 0.12) x 10(16) and (1.41 +/- 0.13) x 10(16) spins/g. The low-temperature
      spectra of oxygenated myocardium contained a predominant signal from a S3 Fe-S
      center and weak signals from N1b, N2, N3, N4 and S1 centers. Global ischemia
      caused cardinal changes in the redox state of the mitochondrial respiratory
      chain. The low-temperature EPR spectrum now contained intensive signals from most
      Fe-S centers. The amount of coenzyme Q10 semiquinones decreased during global
      ischemia, but the content of flavosemiquinones increased. The line width of the
      signal of the ischemic heart was 1.28 +/- 0.03 mT, and its intensity corresponded
      (3.16 +/- 0.94) x 10(16) spins/g. The spin-trapping experiments with TEMPONE-H
      showed that the rate of oxyradical generation in isolated cardiomyocytes
      essentially increased after hypoxia or on adding rotenone and antimycin A. It
      became equal to 4.2 +/- 0.3, 8.2 +/- 0.6 and 7.1 +/- 0.5 nmol/min mg-1
      mitochondrial protein, respectively. The maximal stimulatory effect was observed
      in the presence of both inhibitors. The addition of superoxide dismutase, but not
      catalase, suppressed the formation of oxyradicals.

PMID- 9266506
TI  - Suppression of the formation of megamitochondria by scavengers for free radicals.
AB  - In the present study we have attempted to suppress the formation of
      megamitochondria by scavengers for free radicals since conditions for the
      formation of megamitochondria are often intimately related to the generation of
      free radicals. We employed three different experimental conditions to induce
      megamitochondria in the liver: ethanol, hydrazine and chloramphenicol (CP).
      Scavengers for free radicals tested were: alpha-tocopherol, coenzyme Q10(CoQ10)
      and 4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl(4-OH-TEMPO). Allopurinol
      (AP), a xanthine oxidase inhibitor, was also tested. Results obtained were as
      follows. (1) Changes observed in the liver of animals treated with ethanol,
      hydrazine or CP were: formation of megamitochondria; decreases in the body weight
      and the weight of the liver; remarkable increases in the level of lipid
      peroxidation; increases in the activity of xanthine oxidase. (2) 4-OH-TEMPO was
      most effective in improving these changes. A mechanism of the formation of
      megamitochondria is proposed stressing the role of free radicals in the
      mechanism.

PMID- 9266507
TI  - Mechanisms and dynamics of antioxidant action of ubiquinol.
AB  - The mechanisms and dynamics of antioxidant action of ubiquinol have been studied.
      Ubiquinol scavenges peroxyl radical faster than alpha-tocopherol. However, it is
      autooxidized rapidly to give hydroperoxyl radical and/or superoxide and hence its
      antioxidant potency is smaller than that of alpha-tocopherol. The side chain of
      ubiquinol reduces the mobility between the membranes. It was concluded that
      ubiquinol acts as a potent antioxidant in combination with alpha-tocopherol.

PMID- 9266508
TI  - Cytosolic NADPH-UQ reductase-linked recycling of cellular ubiquinol: its
      protective effect against carbon tetrachloride hepatotoxicity in rat.
AB  - To confirm whether or not cytosolic NADPH-UQ reductase is involved in the
      recycling of cellular ubiquinol (UQH2) consumed during lipid peroxidation, the
      effect of a UQ-10 supplement on the NADPH-UQ reductase and cellular defense
      against oxidative damage in rat livers was investigated. Supplements of UQ-10 for
      14 days enhanced the levels of UQH2-10 and NADPH-UQ reductase in rat livers
      without any appreciable changes in other antioxidant contents and related enzyme
      activities. However, the injection of carbon tetrachloride (CCl4) into the rats
      induced lipid peroxidation and decreased the cellular UQH2-10 contents (and
      increased equivalent amounts of UQ-10), as well as decreasing the ascorbic acid,
      reduced glutathione (GSH) and alpha-tocopherol contents of the rat livers.
      Administration of the UQ-10 supplement prior to the CCl4 treatment spared alpha
      tocopherol (but not GSH or ascorbic acid), inhibited lipid peroxidation, and thus
      improved CCl4-induced hepatitis. These findings support the notion that NADPH-UQ
      reductase in cytosol is the enzyme responsible for the regeneration of UQH2 from
      UQ formed by lipid peroxidation in cells.

PMID- 9266509
TI  - Plasma ratio of ubiquinol and ubiquinone as a marker of oxidative stress.
AB  - Oxidative stress is defined as a disturbance in the prooxidant-antioxidant
      balance in favor of the former and has been suggested to be a relevant factor in
      aging as well as in different pathological conditions, such as heart attack,
      diabetes, and cancer. Ubiquinol is very sensitive against oxygen radicals and
      gives ubiquinone as an oxidation product. Therefore, the ratio of ubiquinol to
      ubiquinone should be a good marker of oxidative stress because of its definition.
      A method for the simultaneous detection of ubiquinol-10 and ubiquinone-10 in
      human plasma is described. Heparinized human plasma was mixed with 5 volumes of
      methanol and 10 volumes of hexane. After vigorous shaking and centrifugation, the
      hexane phase (5 microliters) was injected immediately and directly on to reverse
      phase HPLC equipped with an on-line reduction column and an electrochemical
      detector in order to avoid the oxidation of ubiquinol to ubiquinone. It was found
      that the ratio of ubiquinol-10 to ubiquinone-10 was about 95/5 in human plasma
      from healthy donors. A significant increase in the oxidized form (ubiquinone-10)
      content was observed in plasmas of patients with hepatitis, cirrhosis, and
      hepatoma when compared with normal subjects, suggesting increased oxidative
      stress in these patients.

PMID- 9266510
TI  - Inhibition of LDL oxidation by ubiquinol-10. A protective mechanism for coenzyme
      Q in atherogenesis?
AB  - The oxidation of low density lipoprotein (LDL) is now commonly regarded as an
      important early event in atherogenesis. As such there is considerable interest in
      the ability of antioxidant supplementation to attenuate LDL oxidation and hence
      atherosclerosis. A majority of studies on LDL antioxidation have focused on alpha
      tocopherol (alpha-TOH), biologically and chemically the most active form of
      vitamin E and quantitatively the major lipid-soluble antioxidant in extracts
      prepared from human LDL. In addition to alpha-TOH, circulating LDL also contains
      low levels of ubiquinol-10 (CoQ10H2; the reduced form of coenzyme Q). Recent
      studies have shown that in intact, isolated LDL, alpha-TOH can act as either an
      anti- or prooxidant for the lipoprotein's lipids. This article reviews the
      molecular action of alpha-TOH in LDL undergoing radical-initiated oxidation, and
      how the presence of CoQ10H2 suppresses the pro-oxidant or complements the
      antioxidant activity of the vitamin. We also comment on the plasma and intimal
      levels of alpha-TOH and CoQ10H2 in patients suffering from coronary artery
      disease and discuss the potential implications of these results for
      atherogenesis.

PMID- 9266511
TI  - Oxidation of LDL and their subfractions: kinetic aspects and CoQ10 content.
AB  - Coenzyme Q10 in its reduced form, ubiquinol-10, although present in LDL at
      concentrations considerably lower than that of alpha-tocopherol, exerts a potent
      antioxidant action in this class of lipoproteins. Previous studies indicated that
      the content of CoQ10 is the lowest in the densest subfraction of LDL, i.e. LDL3,
      which is commonly regarded as the most peroxidizable and atherogenic one. These
      levels were associated with the highest levels of hydroperoxides detectable in
      the three subclasses. Enrichment of LDL with CoQ10, by means of exogenous
      supplementation, resulted in a significant increase of CoQ10 in LDL, mainly in
      LDL3, and in a lower extent of peroxidizability. Spontaneous oxidation of
      ubiquinol was monitored in plasma and in LDL of unsupplemented and of
      supplemented subjects and the time-course of oxidation was found considerably
      slower in CoQ10-enriched LDL. The lagphase of conjugated dienes formation upon
      induced oxidation was significantly correlated with the absolute content of
      ubiquinol-10. Distribution of CoQ10 among different classes of plasma
      lipoproteins was also studied: about 60% of plasma CoQ10 was found associated
      with LDL.

PMID- 9266512
TI  - Ubiquinol-10 and total peroxyl radical trapping capacity of LDL lipoproteins
      during aging: the effects of Q-10 supplementation.
AB  - Evidence is rapidly accumulating that oxidative modification of low density
      lipoprotein (LDL) may play an important role in the pathogenesis of
      atherosclerosis. In this study we measured the total peroxyl radical trapping
      capacity of human plasma LDL phospholipids (TRAPLDL) with a luminescent method.
      The study was carried out with 70 healthy volunteers, aged 28-77. In males an age
      related decrease in TRAPLDL was observed. In the age group under 50 years the
      mean TRAPLDL was 31.36 +/- 1.45 pmol peroxyl radicals/nmol Pi; among those over
      50 years it was significantly lower at 26.67 0.94 pmol/nmol Pi. As regards the
      components of TRAPLDL, the concentration of LDL-ubiquinol did not change and a
      non-significant decrease in the LDL-tocopherol concentration was detected with
      age. In females, the mean TRAPLDL, LDL-ubiquinol-10 and tocopherol concentrations
      did not differ between the age groups. When 17 of the participants were given
      coenzyme Q10 (Q10) supplementation, 100 mg/day, a highly significant increase in
      LDL-ubiquinol concentration was detected. Our results indicate that LDL
      antioxidant defenses tend to decrease with age in the Finnish male population.
      The decline is most significant in males under 50 years; in older age groups the
      values remain stable at a low level. Q10 supplementation doubles the number of
      ubiquinol-10-containing LDL molecules and may therefore have an inhibitory effect
      on LDL oxidation.

PMID- 9266513
TI  - Sensitivity to treatment with polyunsaturated fatty acids is a general
      characteristic of the ubiquinone-deficient yeast coq mutants.
AB  - The biosynthesis of ubiquinone (Q) and the functional consequences of Q
      deficiency was studied in the yeast Saccharomyces cerevisiae. Lipid extracts were
      prepared from various respiratory deficient mutants grown in the presence of p-[U
      14C]hydroxybenzoic acid. Q mutant strains harboring mutations in the coq3, coq4,
      coq5, coq6, coq7, or coq8 genes were unable to produce Q and accumulated an early
      intermediated that corresponded to 3-hexaprenyl-4-hydroxybenzoic acid. Several
      respiratory deficient yeast including both nuclear and mitochondrial petite
      mutant strains, retain the ability to produce Q. Thus, the inability to produce Q
      is a specific phenotype manifested in the class of mutants termed 'coq'. Previous
      studies described the enhanced sensitivity of the Q-deficient yeast strain
      containing a deletion in the COQ3 gene to the products of autoxidized
      polyunsaturated fatty acids (Do et al., 1996, Proceeding of the National Academy
      of Science USA, 93, 7534-7539). The results presented here show this to be a
      general phenotype resulting from Q-deficiency, as all of the coq mutant yeast
      strains tested exhibit hypersensitivity to polyunsaturated fatty acid treatment.

PMID- 9266514
TI  - Coenzyme Q content depends upon oxidative stress and dietary fat unsaturation.
AB  - The presence of Coenzyme Q (CoQ) in food, its role in cellular bioenergetics and
      antioxidant protection and the key role played by dietary fatty acids on membrane
      structure support the interest for a wide research concerning the relationship
      between dietary fats, CoQ content and biochemical behaviour. Several models of
      peroxidative stress 'in vivo' have been extensively investigated in our
      laboratory, with particular regards to the influence of dietary fat upon
      mitochondrial CoQ levels. First studies showed that the unsaturation degree of
      dietary fat leads to different CoQ9 and CoQ10 mitochondrial contents. The highest
      levels were found using polyunsaturated fat. A significant CoQ9 decrease after
      adriamycin peroxidative induction was found when dietary fat was polyunsaturated;
      on the contrary, a light increase was found in the case of monounsaturated fat.
      Another example of oxidative stress is that produced by food frying. The results
      obtained were in some cases similar to those of the previous experimental design:
      in fact monounsaturated dietary fats increased CoQ mitochondrial contents,
      whereas the polyunsaturated ones decreased CoQ levels. Finally, the combined
      effect of physical exercise and dietary fats on tissue and plasma CoQ levels has
      been studied. CoQ levels did not change during aerobic performances when dietary
      fat was monounsaturated whereas light increases were detected in the case of
      polyunsaturated fats. On the contrary, in anaerobic conditions, CoQ levels
      clearly increased with monounsaturated fats and no alterations were found in the
      case of polyunsaturated ones.

PMID- 9266515
TI  - Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA
      reductase inhibitors.
AB  - Coenzyme Q10 (ubiquinone) the essential mitochondrial redox-component and
      endogenous antioxidant, packaged into the LDL + VLDL fractions of cholesterol,
      has been suggested as an important anti-risk factor for the development of
      atherosclerosis as explained by the oxidative theory. Forty-five
      hypercholesterolemic patients were randomized in a double-blind trial in order to
      be treated with increasing dosages of either lovastatin (20-80 mg/day) or
      pravastatin (10-40 mg/day) over a period of 18 weeks. Serum levels of coenzyme
      Q10 were measured parallel to the levels of cholesterol at baseline on placebo
      and diet and during active treatment. A dose-related significant decline of the
      total serum level of coenzyme Q10 was found in the pravastatin group from 1.27 +/
      0.34 at baseline to 1.02 +/- 0.31 mmol/l at the end of the study period (mean +/
      S.D.), P < 0.01. After lovastatin therapy the decrease was significant as well
      and more pronounced, from 1.18 +/- 0.36 to 0.84 +/- 0.17 mmol/l, P < 0.001.
      Although HMG-CoA reductase inhibitors are safe and effective within a limited
      time horizon, continued vigilance of a possible adverse consequence from coenzyme
      Q10 lowering seems important during long-term therapy.

PMID- 9266516
TI  - Treatment of hypertrophic cardiomyopathy with coenzyme Q10.
AB  - Hypertrophic cardiomyopathy (HCM) is manifested by severe thickening of the left
      ventricle with significant diastolic dysfunction. Previous observations on the
      improvement in diastolic function and left ventricular wall thickness through the
      therapeutic administration of coenzyme Q10 (CoQ10) in patients with hypertensive
      heart disease prompted the investigation of its utility in HCM. Seven patients
      with HCM, six non-obstructive and one obstructive, were treated with an average
      of 200 mg/day of CoQ10 with mean treatment whole blood CoQ10 level of 2.9
      micrograms/ml. Echocardiograms were obtained in all seven patients at baseline
      and again 3 or more months post-treatment. All patients noted improvement in
      symptoms of fatigue and dyspnea with no side effects noted. The mean
      interventricular septal thickness improved significantly from 1.51 +/- 0.17 cm to
      1.14 +/- 0.13 cm, a 24% reduction (P < 0.002). The mean posterior wall thickness
      improved significantly from 1.37 +/- 0.13 cm to 1.01 +/- 0.15 cm, a 26% reduction
      (P < 0.005). Mitral valve inflow slope by pulsed wave Doppler (EF slope) showed a
      non-significant trend towards improvement, 1.55 +/- 0.49 m/sec2 to 2.58 +/- 1.18
      m/sec2 (P < 0.08). The one patient with subaortic obstruction showed an
      improvement in resting pressure gradient after CoQ10 treatment (70 mmHg to 30
      mmHg).

PMID- 9266517
TI  - Recovery of the systolic time intervals by coenzyme Q10 in patients with a load
      induced cardiac dysfunction.
AB  - In patients with a load-induced cardiac dysfunction (LCD), the left ventricular
      (LV) stroke work is supernormal at rest, but then becomes subnormal during
      handgrip (HG). The LCD usually occurs in children with the mitral valve prolapse
      (MVP). Our catheterization study revealed that the end-diastolic pressure (EDP)
      of both ventricles was elevated in LCD patients. In this study, the LV and right
      ventricular (RV) systolic time (ET) were measured by echocardiograms. The mitral
      inflow peak velocities, E and A, were also measured by the pulsed Doppler method.
      Subjects were divided into four groups, each consisting of 16 individuals: group
      1, normal children; group 2, LCD patients; group 3, recovered children from LCD,
      the same individuals as group 2, but after coenzyme Q10 (CoQ) therapy; and group
      4, asymptomatic children with MVP. In group 2, the mean PEP and PEP/ET were
      significantly smaller and the peak A velocity was significantly larger than in
      groups 1, 3 and 4. Among groups 1, 3 and 4, no intergroup differences were found
      regarding the PEP/ET and A. In LCD patients, a depressed inotropic state of the
      myocardium may result in a high EDP due to the Frank-Starling mechanism, and such
      a high EDP may then cause STI changes and a large A velocity. CoQ may also return
      abnormal STIs in LCD patients to normal, probably by improving the inotropic
      state and, as a consequence, reducing the high EDP of the LV and RV to a normal
      level.

PMID- 9266518
TI  - Treatment of congestive heart failure with coenzyme Q10 illuminated by meta
      analyses of clinical trials.
AB  - The purpose of this was to investigate the effect of coenzyme Q10 (CoQ10) in
      patients with congestive heart failure (CHF) by measuring the possible
      improvement of certain relevant hemodynamic heart parameters. A statistic
      aggregation method know as a meta-analysis was used to measure the changes in the
      cardiac parameters. To begin with we collected the total number of randomized
      controlled trials and from a total of 14 studies published in the period of 1984
      1994, eight studies met our inclusion criteria. The rest were excluded because of
      a lack of data which made a meta-analysis impossible. The relevant effect
      parameters investigated were stroke volume (SV), cardiac output (CO), ejection
      fraction (EF), cardiac index (CI), end diastolic volume index (EDVI), systolic
      time intervals (PEP/LVET) and total work capacity (Wmax). Seven meta-analyses
      were performed, one for each of the parameters, and the calculated effect sizes
      were all positive. Statistical significance could be demonstrated for all of the
      parameters except the PEP/LVET and Wmax thereby indicating an improvement of
      greater or lesser magnitude in the CoQ10 group as opposed to the placebo group.
      Accordingly, the average patient in the CoQ10 group had a better score with
      regard to SV and CO than 76 and 73% respectively of the patients in the placebo
      group. In conclusion, supplemental treatment of CHF with CoQ10 is consistent with
      an improvement of SV, EF, CO, CI and EDVI. Homogeneity could be established for
      SV and CO. Additional clinical trials of the effect of CoQ10 on CHF are
      necessary, but, on the basis of the evidence currently available, the possibility
      remains that CoQ10 will receive a well-documented role as an adjunctive treatment
      of CHF.

PMID- 9266519
TI  - Coenzyme Q10 in the central nervous system and its potential usefulness in the
      treatment of neurodegenerative diseases.
AB  - Coenzyme Q10 is an essential cofactor of the electron transport chain and is an
      antioxidant. We examined the effects of oral feeding with coenzyme Q10 in young
      animals on brain concentrations. Feeding with coenzyme Q10 at a dose of 200 mg/kg
      for 1-2 months in young rats resulted in significant increases in liver
      concentrations, however, there was no significant increase in brain
      concentrations of either reduced- or total coenzyme Q10 levels. Nevertheless
      there was a reduction in malonate-induced increases in 2,5 dihydroxybenzoic acid
      to salicylate, consistent with an antioxidant effect. In other studies we found
      that oral administration of coenzyme Q10 significantly reduced increased
      concentrations of lactate in the occipital cortex of Huntington's disease
      patients. These findings suggest that coenzyme Q10 might be useful in treating
      neurodegenerative diseases.

PMID- 9266520
TI  - Diabetes mellitus associated with 3243 mitochondrial tRNA(Leu(UUR)) mutation:
      clinical features and coenzyme Q10 treatment.
AB  - Diabetes mellitus associated with mitochondrial tRNA mutation at position 3243(DM
      Mt3243) is a new disease. Patients have a distinctly different picture from MELAS
      (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes).
      During observations at the Saiseikai Central Hospital, the following findings
      were noted in DM-Mt3243 patients: DM-Mt3243 patients are diagnosed earlier with
      diabetes, compared to NIDDM (non-insulin dependent diabetes mellitus) controls
      without family history. DM-Mt3243 patients often need insulin more often than
      NIDDM controls without family history. Post-treatment neuropathy and insulin
      edema are often found in DM-Mt3243, and the two phenomena possibly have a similar
      pathophysiology related to mitochondrial dysfunction. Ambiguous psychiatric
      disorders of functional psychosis are observed frequently in DM-Mt3243. Mild
      headache is common in DM-Mt3243 cases. Ambiguous neuromuscular abnormalities such
      as sleep disturbance, paresthesia of the legs, edema of the legs, and palpitation
      may be symptoms associated with mitochondrial dysfunction in DM-Mt3243. Coenzyme
      Q may be effective in the relief of these neuromuscular symptoms.

PMID- 9266521
TI  - Could coenzyme Q10 affect hemostasis by inhibiting platelet vitronectin
      (CD51/CD61) receptor?
AB  - Improved cardiovascular morbidity and mortality have been observed in several
      clinical studies of dietary supplementation with coenzyme Q10 (CoQ10,
      ubiquinone). Several mechanisms have been proposed to explain the effects of
      CoQ10. One attractive theory links ubiquinone with the inhibition of platelets.
      The effect of CoQ10 intake on platelet surface antigens, and certain hemostatic
      parameters was examined in 15 humans and 10 swine. Study participants received
      100 mg of CoQ10 twice daily in addition to their usual diet for 20 days resulting
      in a three-fold increase of total serum CoQ10 level. We observed a decline in
      plasma fibronectin (-20.2%), thromboxane B2 (-20.6%), prostacyclin (-23.2%), and
      endothelin-1 (-17.9%) level. Significant inhibition of vitronectin receptor
      expression was observed consistently throughout ubiquinone treatment. Inhibition
      of the platelet vitronectin receptor is a direct evidence of a link between
      dietary CoQ10 intake, platelets, and hemostasis. These findings may contribute to
      the observed clinical benefits by a diminished incidence of thrombotic
      complications in such patients.

PMID- 9266522
TI  - The mechanisms of coenzyme Q10 as therapy for myocardial ischemia reperfusion
      injury.
AB  - It has been hypothesized that CoQ10 (CoQ) pretreatment protects myocardium from
      ischemia reperfusion (I/R) injury by its ability to increase aerobic energy
      production as well as its activity as an antioxidant. Isolated hearts from rats
      pretreated with either CoQ 20 mg/kg i.m. and 10 mg/kg i.p. or vehicle 24 and 2 h
      prior to the experiment, were subjected to 15 min of equilibration (EQ), 25 min
      of ischemia, and 40 min of reperfusion (RP). Developed pressure, +/-dp/dt,
      myocardial oxygen consumption, and myocardial aerobic efficiency (DP/MVO2) were
      measured. 31P NMR spectroscopy was used to determine ATP and PCr concentrations.
      Lucigenin-enhanced chemiluminescence of the coronary sinus effluent was utilized
      to determine oxidative stress through the protocol. CoQ pretreatment improved
      myocardial function after ischemia reperfusion. CoQ pretreatment improved
      tolerance to myocardial ischemia reperfusion injury by its ability to increase
      aerobic energy production, and by preserving myocardial aerobic efficiency during
      reperfusion. Furthermore, the oxidative burst during RP was diminished with CoQ.
      Similarly it was hypothesized that CoQ protected coronary vascular reactivity
      after I/R via an antioxidant mechanism. Utilizing a newly developed lyposomal CoQ
      preparation given i.v. 15 min prior to ischemia, ischemia reperfusion was carried
      out on Langendorff apparatus as previously described. Just prior to ischemia and
      after RP, hearts were challenged with bradykinin (BK) and sodium nitroprusside
      (SNP) and change in coronary flow was measured. CoQ pretreatment protected
      endothelial-dependent and endothelial-independent vasodilation after I/R. We
      conclude that CoQ pretreatment protects coronary vascular reactivity after I/R
      via OH radical scavenger action.

PMID- 9266523
TI  - The effect of ethanol and/or food restriction on coenzyme Q in liver in rats.
AB  - The individual and combined effects of ethanol and lovastatin on rats and their
      prevention by supplemental coenzyme Q10 (CoQ10) was studied. The ethanol and
      lovastatin findings are reported elsewhere. This paper focuses on the food
      restriction which occurred in rats fed 35% of energy as ethanol and those control
      rats pair-fed to the 35% of energy as ethanol group. Six groups of rats received
      35% of energy as ethanol (with or without lovastatin and/or CoQ10 treatment). One
      group served as a 0% ethanol ad libitum control and one 0% ethanol control group
      was pair-fed to the 35% ethanol group. Rats receiving 35% of energy as ethanol
      and their pair-fed controls consumed 83% of the energy/day consumed by the ad
      libitum controls. This was consistent regardless of lovastatin or CoQ10
      treatment. Weight gains were 84% of control. The energy reduction was
      consistently associated with a substantial (48%+) increase in liver CoQ9
      concentrations. Reports by others of associations between food restriction and
      increased longevity in rodents has focused on a decrease in oxidant damage in
      tissues of food restricted animals. The increase in CoQ levels in the food
      restricted animals would result in an increase in antioxidant protection and
      might explain the observed increases in longevity.

PMID- 9266524
TI  - The effect of coenzyme Q10 on sperm motility and function.
AB  - In sperm cells, the majority of coenzyme Q10 (CoQ10) an energy promoting agent
      and antioxidant, is concentrated in the mitochondria of the midpiece, so that the
      energy for movement and all other energy-dependent processes in the sperm cell
      also depend on the availability of CoQ10. The reduced form of CoQ10-ubiquinol
      also acts as an antioxidant, preventing lipid peroxidation in sperm membranes.
      The objective of the study was to evaluate the effect of CoQ10 on sperm motility
      in vitro, after incubation with 38 samples of asthenospermic and normal motility
      sperm, and to evaluate the effect of CoQ10 administration in vivo in 17 patients
      with low fertilization rates after in vitro fertilization with intracytoplasmic
      sperm injection (ICSI) for male factor infertility. All 38 sperm samples from
      patients registered in our infertility clinic had normal concentrations and
      morphology. Of these, 16 patients had normal motility (mean 47.5%) and 22
      patients were asthenospermic (mean motility 19.1%). Sperm samples were divided
      into four equal parts and incubated for 24 h in: HAM's medium alone, in HAM's
      medium with 1% DMSO and HAM's with 5 microM or 50 microM CoQ10. While no
      significant change in motility after incubation was observed in the samples with
      initial normal motility, a significant increase in motility was observed in the
      50 microM CoQ10 subgroup of sperm from asthenospermic men, with a motility rate
      of 35.7 +/- 19.5%, as compared to 19.1 +/- 9.3% in the controls (P < 0.05). The
      17 patients with low fertilization rates after ICSI were treated with oral CoQ10,
      60 mg/day, for a mean of 103 days before the next ICSI treatment. No significant
      change was noted in most sperm parameters, but a significant improvement was
      noted in fertilization rates, from a mean of 10.3 +/- 10.5% in their previous
      cycles, to 26.3 +/- 22.8% after CoQ10 (P < 0.05). In conclusion, the
      administration of CoQ10 may result in improvement in sperm functions in selective
      patients. Further investigation into the mechanisms related to these effects is
      needed.

PMID- 9266525
TI  - The protective role of ubiquinol-10 against formation of lipid hydroperoxides in
      human seminal fluid.
AB  - Defective sperm function in infertile men has been associated with increased
      lipid peroxidation and impaired function of antioxidant defenses in spermatozoa.
      Evidence strongly suggests that CoQ10, a lipid-soluble component of the
      respiratory chain acts, in its reduced form (ubiquinol), as a potent antioxidant
      in various biological systems, such as lipoproteins and membranes. In this study
      we assayed CoQ10 content in both the reduced and oxidized form
      (ubiquinol/ubiquinone), and hydroperoxide levels in seminal plasma and seminal
      fluid from 32 subjects with a history of infertility. Our results showed a
      significant correlation between ubiquinol content and sperm count (r = 0.62; P <
      0.05) in seminal plasma. An inverse correlation between ubiquinol content and
      hydroperoxide levels both in seminal plasma and in seminal fluid (r = -0.56; P =
      0.01) was found. Using multiple regression analysis we also found a strong
      correlation among sperm count, motility and ubiquinol-10 content (P < 0.01) in
      seminal fluid. An inverse correlation between ubiquinol/ubiquinone ratio and
      percentage of abnormal morphology was also observed in total fluid. These results
      suggest that ubiquinol-10 inhibits hydroperoxide formation in seminal fluid and
      in seminal plasma. Since peroxidation in sperm cells is an important factor
      affecting male infertility, ubiquinol could assume a diagnostic and/or a
      therapeutic role in these patients.

PMID- 9266526
TI  - Lipid peroxidation and antioxidants in newborns.
AB  - The aim of this investigation was to elucidate a possible correlation between
      lipid peroxidation, antioxidant concentrations and erythrocyte membrane fluidity
      in plasma from newborns. Ten healthy newborns were recruited. Venous blood
      samples were collected at birth, and thereafter at 3 and 72 h postnatal age. The
      following parameters were assessed: hydroperoxides, Coenzyme Q10 and alpha
      tocopherol both in plasma and in erythrocyte membranes, and fluorescence
      polarization (as a tool for assessing membrane fluidity). Hydroperoxides were
      shown to be high in erythrocyte membranes at birth and significantly decreased at
      3 and 72 h after birth. In the erythrocyte membranes, coenzyme Q10 content showed
      an opposite behaviour with respect to the plasma compartment. Membrane fluidity
      appeared unchanged even in the presence of the above mentioned modifications.

PMID- 9266527
TI  - Rabbit liver mitochondria coenzyme Q10 and hydroperoxide levels: an experimental
      model of atherosclerosis.
AB  - The development of the atherosclerosis is mediated by the accumulation of
      oxidized lipids in the arterial wall. There is a relationship between average
      intake of dietary fat, its quality, and incidence of atherosclerosis. The goal of
      this work was to study the effect of different dietary fats on the coenzyme Q10
      and hydroperoxide content of liver mitochondria in rabbits affected by an induced
      atherosclerosis. The results show that the induction of experimental
      atherosclerosis leads to a significant increase in hydroperoxides of rabbit liver
      membrane mitochondria and to a significant drop in the content of CoQ10.
      Furthermore, treatment of atherosclerotic rabbits with different diets resulted
      in an increase of membrane hydroperoxides in the group fed sunflower oil whereas
      the increase was significantly lower for animals fed virgin olive oil and fish
      oil stabilized with vitamin E (1 g/kg). CoQ10 levels only recovered partially in
      all groups; however, values in the sunflower oil were significantly lower as
      compared to corresponding values of the other groups. The use of either virgin
      olive oil or vitamin E stabilized fish oil in the dietary treatment of
      atherosclerosis appears to be a valid alternative for maintaining adequate levels
      of CoQ10 and hydroperoxides in liver mitochondria.

PMID- 9266528
TI  - Q10 therapy in patients with idiopathic Parkinson's disease.
AB  - A 3-month open-label trial was performed to evaluate the efficacy of 200 mg Q10
      daily in 10 patients with Parkinson's disease. Motor performance was assessed
      with UPDRS and motor tests. There was no significant effect on the clinical
      ratings.

PMID- 9266529
TI  - Metabolic and antioxidant markers in the plasma of sportsmen from a Mediterranean
      town performing non-agonistic activity.
AB  - It has been widely indicated that several pathological conditions depend upon
      concomitant risk factors rather than a unique one and that also the putative
      protective factors do not act alone. For these reasons it could be useful to
      consider subjects that present sufficiently homogeneous lifestyles (i.e.
      nutrition and physical activity). We carried out an investigation in a free
      living community in order to clarify the possible correlations and differences
      among plasma metabolic and antioxidant markers in non-agonistic athletes. When
      subjects were divided in two main groups according to age (35-44 and 45-54 years)
      without considering the activity they performed, Duncan's analysis of variance
      revealed that they showed similar characteristics and only triglyceride levels
      were different. A clear negative correlation was found between vitamin E and
      VO2max in both age groups, a negative correlation was also found between CoQ10
      and VO2max in the younger subjects and finally CoQ10 and vitamin E were also
      positively correlated in this first group. It appears, therefore, that people
      with a higher aerobic capacity have lower circulating levels of antioxidants.

PMID- 9266530
TI  - Dietary restriction affects antioxidant levels in rat liver mitochondria during
      ageing.
AB  - Six experimental groups of young (7-month-old) and aged (24-32-month-old) rats,
      underwent different dietary manipulations (i.e. dietary restriction and/or a
      vitamin E-depleted diet), and their liver mitochondria were assayed for several
      antioxidants and peroxidation markers. Glutathione levels were affected both by
      age and dietary treatment. Coenzyme Q9 and C0Q10 showed the highest levels in the
      oldest rats where ageing, as well as other oxidative stresses, could induce
      ubiquinone biosynthesis.

PMID- 9266531
TI  - Coenzyme Q10 in the diet--daily intake and relative bioavailability.
AB  - The coenzyme Q10 content of the average Danish diet was estimated from
      consumption data and from analysis of food items to be 3-5 mg coenzyme Q10 per
      day, primarily derived (64% of the total) from meat and poultry. To investigate
      if coenzyme Q10 was absorbed to any significant degree from a food item, a
      randomized cross-over study with single doses of coenzyme Q10 (30 mg/person),
      administered either as a meal or as capsules, was carried out in healthy
      subjects. The serum coenzyme Q10 concentration increased significantly, and the
      maximum concentrations did not differ significantly for the two forms of
      administration. The study indicates that coenzyme Q10 is present in food items
      and absorbed to a significant degree. Thus, dietary coenzyme Q10 may contribute
      to the plasma coenzyme Q10 concentration.

PMID- 9266532
TI  - T-2 toxin-induced DNA damage in mouse livers: the effect of pretreatment with
      coenzyme Q10 and alpha-tocopherol.
AB  - Active oxygen species are reported to cause organ damage. This study was
      therefore designed to determine whether oxidative stress contributed to the
      initiation or progression of hepatic DNA damage produced by T-2 toxin. The aim of
      the study was also to investigate the behaviour of the antioxidants coenzyme Q10
      (CoQ10), and alpha-tocopherol (vitamin E) against DNA damage in the livers of
      mice fed T-2 toxin. Treatment of fasted mice with a single dose of T-2 toxin (1.8
      or 2.8 mg/kg body weight) by oral gavage led to 76% hepatic DNA fragmentation. T
      2 toxin also decreased hepatic glutathione (GSH) levels markedly. Pretreatment
      with CoQ10 (6 mg/kg) together with alpha tocopherol (6 mg/kg) decreased DNA
      damage. The CoQ10 and vitamin E showed some protection against toxic cell death
      and glutathione depletion caused by T-2 toxin. Oxidative damage caused by T-2
      toxin may be one of the underlying mechanisms for T-2 toxin-induced cell injury
      and DNA damage, which eventually lead to tumourigenesis.

PMID- 9266533
TI  - Evaluation of the possible role of coenzyme Q10 and vitamin E in juvenile
      neuronal ceroid-lipofuscinosis (JNCL).
AB  - The juvenile type of neuronal ceroid lipofuscinosis (JNCL) is a recessively
      inherited, progressive neurodegenerative disease. In this study the levels of the
      antioxidant factors coenzyme Q10 (CoQ10) and vitamin E (alpha-tocopherol) were
      measured in plasma samples of 29 JNCL patients and compared to 48 healthy
      controls. A significant reduction of the coenzyme Q10 level (0.59 +/- 0.25
      microgram/ml) was observed in JNCL patients when compared to control subjects
      (0.80 +/- 0.26 microgram/ml). The level of vitamin E was also reduced markedly in
      JNCL patients when compared to controls (10.4 +/- 4.1 and 12.1 +/- 4.5
      micrograms/ml, respectively). The low levels of CoQ10 and vitamin E in JNCL
      patients may indicate an impaired antioxidant protection in this disease.

PMID- 9266534
TI  - Changes in mitochondrial complex I activity and coenzyme Q binding site in
      Leber's hereditary optic neuropathy (LHON).
AB  - The complex I function in sub-mitochondrial particles was studied in platelets
      from patients and healthy carriers with 11778/ND4 or 3460/ND1 mtDNA point
      mutations associated with LHON. Both 11778/ND4 and 3460/ND1 mutations induced
      rotenone resistance and 11778/ND4 showed an increased K(m) for ubiquinol-2 with
      respect to the control group. It was concluded that even with different
      pathogenic mechanisms both mutations affect the quinone binding site of complex
      I.

PMID- 9266535
TI  - Saturation kinetics of coenzyme Q in NADH oxidation: rate enhancement by
      incorporation of excess quinone.
AB  - In beef heart mitochondria it has been found that the Km for coenzyme Q10 of the
      NADH oxidation system is in the range of the membrane concentration of the
      quinone; this is contrary to succinate oxidation which is in Vmax with respect to
      quinone content. The same proportional difference between the two systems is
      maintained in their affinities for the exogenous acceptor CoQ1 in non-extracted
      mitochondria. The Km of succinate- coenzyme Q reductase for CoQ1 is reversibly
      lowered in CoQ-depleted mitochondria; while in contrast the Km for NADH-coenzyme
      Q reductase is reversibly increased by CoQ extraction. Incorporation of exogenous
      quinones by co-sonication with submitochondrial particles, as evidenced by
      fluorescence quenching of pyrene, enhances NADH-cytochrome c reductase activity
      in accordance with the lack of saturation of the former system.

PMID- 9266536
TI  - Coenzyme Q changes in liver and plasma in the rat after partial hepatectomy.
AB  - The levels of coenzyme Q were determined in blood plasma and regenerating liver
      mitochondria of hepatectomized rats, using as controls either sham-operated or
      non-operated animals. Mitochondrial CoQ9 content increased in sham-operated rats,
      whereas it was significantly lower in hepatectomized with respect to non-operated
      animals. Plasma CoQ9 levels decreased dramatically in hepatectomized animals, but
      increased strongly in sham-operated in comparison with non-operated rats. The
      data suggest the possibility of a rate-limiting step in CoQ biosynthesis in
      hepatectomized animals.

PMID- 9266537
TI  - Coenzyme Q homologs and vitamin E in synaptic and non-synaptic occipital cerebral
      cortex mitochondria in the ageing rat.
AB  - The coenzyme Q8 (CoQ8) and alpha-tocopherol contents of different mitochondrial
      fractions were investigated from occipital cerebral cortices of different ages.
      The highest CoQ8 and vitamin E concentrations were found in non-synaptic free
      mitochondria (FM) fractions. In several cases heavy mitochondria (HM) fractions
      displayed the lowest values. Occipital cerebral cortex mitochondria contained
      higher CoQ9 and lower CoQ10 amounts than those typical for other brain regions.

PMID- 9266538
TI  - The effect of coenzyme Q10 on the exercise performance of cross-country skiers.
AB  - Coenzyme Q10 supplementation (Bio-Qinon Pharma Nord, 90 mg/day) was studied in a
      double-blind cross-over study of 25 Finnish top-level cross-country skiers. With
      CoQ10 supplementation, all measured indexes of physical performance (AET, ANT and
      VO2Max) improved significantly. During verum supplementation, 94% of the athletes
      felt that the preparation had been beneficial in improving their performance and
      recovery time vs. only 33% in the placebo periods.

PMID- 9266539
TI  - Effects of oral supplementation of coenzyme Q10 on 31P-NMR detected skeletal
      muscle energy metabolism in middle-aged post-polio subjects and normal
      volunteers.
AB  - The effects of oral supplementation of 100 mg coenzyme Q10 (CoQ10) for 6 months
      on muscle energy metabolism during exercise and recovery were evaluated in middle
      aged post-polio (n = 3) and healthy subjects (n = 4) by the use of phosphorus-31
      nuclear magnetic resonance spectroscopy. The metabolic response to isometric
      plantar flexion at 60% of maximal voluntary contraction force (MVC) for 1.5 min
      was determined in gastrocnemius muscles before, after 3- (3MO) and 6-month (6MO)
      of CoQ10 supplementation. The MVC of plantar flexion was unchanged following
      CoQ10 supplementation. The resting Pi/PCr ratio in gastrocnemius muscles of all
      subjects decreased after 3MO- and 6MO-CoQ10 (P < 0.05). The post-polio
      individuals showed a progressive decrease in this ratio, while less pronounced
      changes were observed in the control subjects. Similarly, the post-polio
      individuals showed a lower Pi/PCr ratio at the end of 60% MVC in both 3MO- and
      6MO-CoQ10, whereas no change in the ratio was observed in the control subjects. A
      less pronounced decrease in muscle pH was observed at the end of 60% MVC in both
      3MO- and 6MO-CoQ10 in the post-polio individuals, but not in the control
      subjects. No systematic difference in end-exercise ATP was observed between the
      three phases in both groups. The half-time of recovery for PCr decreased in all
      subjects after 6MO-CoQ10 supplementation (P < 0.05). The results suggest that
      CoQ10 supplementation affects muscle energy metabolism in post-polio individuals
      to a greater extent than in control subjects. The mechanism for this effect is
      not clear, but may involve an effect of CoQ10 on peripheral circulation in the
      calf muscles, its action in mitochondrial oxidative phosphorylation and/or its
      antioxidant potential.

PMID- 9266540
TI  - Refractory congestive heart failure successfully managed with high dose coenzyme
      Q10 administration.
AB  - Coenzyme Q10 (CoQ10) is a critical adjuvant therapy for patients with congestive
      heart failure (CHF), even when traditional medical therapy is successful.
      Adjunctive therapy with Q10 may allow for a reduction of other pharmacological
      therapies, improvement in quality of life, and a decrease in the incidence of
      cardiac complications in congestive heart failure. However, dosing, clinical
      application, bioavailability and dissolution of CoQ10 deserve careful scrutiny
      whenever employing the nutrient. The assessment of blood levels in 'therapeutic
      failures' appears warranted.

PMID- 9266541
TI  - The effect of coenzyme Q10 on blood glucose and insulin requirement in patients
      with insulin dependent diabetes mellitus.

PMID- 9266542
TI  - Melatonin and the immune-hematopoietic system therapeutic and adverse
      pharmacological correlates.
AB  - The pineal neurohormone melatonin functionally synchronizes the photoperiod in
      the organism. In the last decade, it has become increasingly clear that the
      pineal gland and melatonin also play an important immunoregulatory role. T helper
      (Th) cells bear G-protein-coupled melatonin receptors. Activation of melatonin
      receptors enhances the release of Th cell cytokines, such as gamma-interferon and
      interleukin-2, as well as novel opioid cytokines which cross-react
      immunologically with both interleukin-4 and dynorphin B. These mediators may
      counteract secondary immunodeficiencies, protect mice against lethal viral and
      bacterial diseases, synergize with interleukin-2 in cancer patients and affect
      hematopoiesis. Hematopoiesis is apparently influenced by the action of melatonin
      induced opioids on kappa-opioid receptors present on stromal bone marrow cells.
      Most interestingly, gamma-interferon and colony-stimulating factors may modulate
      the production of melatonin in the pineal gland. A hypothetical pineal-immune
      hematopoietic network is, therefore, taking shape. From the immunopharmacological
      point of view, there is a need for clinical studies on the effect of melatonin in
      human immunodeficiency-virus-infected patients and cancer patients. In
      conclusion, melatonin seems to be an important immunomodulatory hormone which
      deserves to be further studied to identify its relevance in immune-based
      diseases, its therapeutic indications and its adverse effects.

PMID- 9266543
TI  - Interaction of cyclophosphamide and ketamine in vivo.
AB  - Cyclophosphamide 100 mg/kg i.p. increased the duration of ketamine-induced
      anesthesia in BALB/c mice by 39%. However, combined action of these two
      substances did not change the number of splenocytes, proliferation of T cells, or
      phagocytic activity of murine peritoneal macrophages against Candida albicans.

PMID- 9266544
TI  - Effects of uncontrollable and controllable electric shocks on T lymphocyte
      subpopulations in the peripheral blood, spleen, and thymus of rats.
AB  - To examine the effects of uncontrollable and controllable electric shocks on the
      immune system in rats, the proportion of CD4+, CD8+ or CD25+ T lymphocytes to
      total lymphocytes was measured in the peripheral blood, spleen, and thymus. The
      rats were given either controllable shocks, identical uncontrollable shocks, or
      no shocks, and then small shocks 24 h later (reinstating shocks). The proportion
      of CD4+ T lymphocytes relative to total lymphocytes in both the peripheral blood
      and spleen of uncontrollable rats (URs) was significantly smaller than was found
      in no-shock rats (NRs). Similarly, the proportion of CD4+ T lymphocytes in the
      thymus of controllable rats (CRs) was significantly smaller than in NRs. In
      contrast, the proportion of CD8+ T lymphocytes in the thymus of URs was
      significantly larger than in NRs and CRs. The CD4+ to CD8+ T lymphocyte ratios
      (CD4+/CD8+ ratios) in the peripheral blood, spleen and thymus of URs were
      significantly smaller than in NRs; also, the ratios in the peripheral blood and
      spleen of URs were significantly smaller than in CRs. The white blood cell (WBC)
      count of URs was significantly smaller than those of NRs and CRs, and the WBC
      count of CRs was significantly smaller than those of NRs and CRs, and the WBC
      count of CRs was significantly smaller than that of NRs. These results suggest
      that decreases in CD4+ T lymphocytes (and/or an increase of CD8+ T lymphocytes)
      in the peripheral blood, spleen, and thymus are caused by uncontrollable stress
      followed by a reinstating stress condition, leading to the decrease of WBC in the
      peripheral blood and decreases in the CD4+/CD8+ ratios in these tissues.

PMID- 9266546
TI  - Effects of bacterial endotoxin on the glucocorticoid feedback regulation of
      adrenocortical response to stress.
AB  - Previous studies have shown that LPS and cytokines modulate the binding of
      glucocorticoids (GCs) in the CNS, and therefore may affect the negative feedback
      exerted by GCs. In this study, we investigated the effect of lipopolysaccharide
      (LPS) on the inhibitory action of GCs upon the adrenocortical response to a
      neural stressful stimulus. Male rats were treated with either LPS (50
      micrograms/kg) or saline for 5 consecutive days. Two days later, the LPS- and
      saline-treated rats were injected intraperitoneally with either dexamethasone (20
      micrograms/kg) or saline and sacrificed 3.5 h later, after exposure to acute
      stressful photic stimulation. In saline-pretreated rats, photic stimulation
      caused a 5-fold increase in serum corticosterone levels compared to basal levels,
      and pretreatment with dexamethasone completely abolished this response. In LPS
      pretreated rats, corticosterone levels following photic stimulation increased 20
      fold, and dexamethasone was ineffective. Additional experiments were conducted to
      examine whether the impairment in the negative feedback was specific to the
      prolonged LPS treatment, rather than to LPS-induced hypersecretion of GCs. In
      groups of rats which were exposed to either daily acoustic stress or daily
      administration of corticosterone (5 mg, twice daily) for 5 days, the pattern of
      corticosterone secretion mimicked the corticosterone secretion induced by LPS. In
      these groups, the adrenocortical response to acute photic stimulation and the
      effect of dexamethasone were similar to saline-pretreated controls. These results
      suggest that LPS impairs the negative feedback of either endogenous or exogenous
      GC upon the adrenocortical response to stress. This finding may be relevant to
      the enhanced adrenocortical activity associated with sepsis and major depression.

PMID- 9266545
TI  - Bacterial endotoxin inhibits LHRH secretion following the increased release of
      hypothalamic GABA levels. Different effects on amino acid neurotransmitter
      release.
AB  - Immune system disorders are often accompanied by alterations in the reproductive
      axis. The bacterial endotoxin (lipopolysaccharide, LPS) has inflammatory effects
      and activates cytokine release in the pituitary and hypothalamus. LPS inhibition
      of luteinizing-hormone-releasing hormone (LHRH) release at the hypothalamic level
      appears to be associated with modifications in the inhibitory GABAergic
      neurotransmitter system. Then, knowing that gamma-aminobutyric acid (GABA)
      mediates other neurotransmitter effects in the central nervous system, the
      possibility arises that this amino acid might mediate the effect of LPS on LHRH
      release by modifying amino acid neurotransmitter release at the hypothalamic
      level. Therefore, the present study was designed to investigate a possible
      mediatory function of the GABAergic system in the LPS-induced inhibition of LHRH
      secretion. To this end, the modifications in the excitatory (glutamate, Glu) and
      inhibitory (taurine, Tau, and GABA) amino acid neurotransmitter release after the
      application of GABA-A and GABA-B antagonists, respectively, were studied and the
      effects of LPS on their release determined. Male rats were decapitated at 9.00 h,
      and the preoptic/mediobasal hypothalamic area (POA/MBH) was dissected and
      superfused with Earle's balanced salt solution. Superfusate fractions were
      collected at 15-min intervals after a 60-min stabilization superfusion period.
      LPS (100 ng/ml) was then added to the superfusion medium over 1 h in three
      different experimental designs: (1) LPS only (2) LPS simultaneously with
      bicuculline (GABA-A antagonist) or with phaclofen (GABA-B antagonist), and (3)
      LPS and subsequently bicuculline or phaclofen, performed in different
      experiments. This was followed by a wash-out period. The POA/MBH fragments were
      then subjected to a 56-mM K+ stimulus. Control POA/MBH fragments were
      continuously superfused with Earle's solution. As expected, LHRH release was
      significantly reduced (p < 0.05) during and following exposure to LPS. At the
      same time, GABA and Tau concentrations increased in the superfusion medium, while
      Glu decreased significantly compared with the control group. The GABA antagonists
      blocked and reversed the LPS effect on LHRH secretion. No significant differences
      were found between the effect of GABA-A and-B receptor antagonists. Meanwhile,
      GABA levels measured in the control group did not increase since they were the
      same as when LPS was added alone. Furthermore, LPS was without effect on Glu and
      Tau release in the presence of the GABA blockers. Therefore, the effect of the
      bacterial endotoxin was blocked. These observations indicate that there is an
      increase in GABA release that becomes significant at the same time when LHRH
      release is decreased. This effect can be blocked by GABA-specific receptor
      blockers. The effect of LPS is thus exerted by increasing GABA. The elevated GABA
      levels may also reduce Glu release and enhance Tau release. These modifications
      in neurotransmitter release may also contribute to LHRH suppression. These
      effects may be explained by the stimulation of cytokines of neuronal and/or glial
      origin that interact with the excitatory and inhibitory amino acids.

PMID- 9266547
TI  - Interleukin-1 beta-induced effects on plasma oxytocin and arginine vasopressin:
      role of adrenal steroids and route of administration.
AB  - The effects of cytokines in stimulating neurohypophysial hormone release have not
      been well characterized. In the present study, we have investigated the effect of
      intraperitoneal injection of recombinant human interleukin (IL)-1 beta on
      oxytocin release in sham-operated controls, adrenalectomized (ADX) rats and ADX
      rats given either low or high doses of the synthesis glucocorticoid
      dexamethasone. In a second study, we determined the effect of central injection
      of IL-1 beta on both oxytocin and arginine vasopressin (AVP) release in sham
      operated and ADX rats. We were unable to demonstrate an increase in plasma
      oxytocin in intact rats in response to intraperitoneal injection of IL-1 beta. In
      contrast, we found a substantial and sustained increase in plasma oxytocin
      concentrations in ADX rats. This stimulation was abolished by treatment with
      dexamethasone at both the low and high doses. Following central injection of IL-1
      beta, we were unable to demonstrate any increase in either oxytocin or AVP,
      despite the ability of this dose of cytokine to stimulate the hypothalamo
      pituitary-adrenal axis, as evidenced by increased circulating corticosterone. It
      appears that circulating glucocorticoids may exert a tonic inhibitory effect on
      the release of oxytocin in response to peripheral stimulation by IL-1 beta.

PMID- 9266548
TI  - Regional production of nitric oxide after a peripheral or central low dose of LPS
      in mice.
AB  - Nitric oxide (NO) plays a key role in the pathophysiology of inflammation and
      sepsis. The regulation of the peripheral inducible NO synthase (iNOS-responsible
      for the massive NO synthesis in inflammation) has been extensively studied in
      sepsis, but little is known about the actual NO production and its dependence on
      the location of the primary stimulus (endotoxin, LPS). We measured the activation
      of the NO pathway after a central (intracerebroventricular) or systemic
      (intravenous) low dose of LPS (2.5 micrograms/mouse) in three ways: the
      accumulation of its stable end products (nitrites/nitrates) in the circulation,
      the induction of iNOS mRNA and the decrease in sodium nitroprusside-dependent ADP
      ribosylation of proteins in the liver and brain. Plasma nitrites/nitrates
      increased after LPS by either route. iNOS mRNA was induced in the liver after
      intravenous and, to a lower extent, in the brain after intracerebroventricular
      LPS. Ex vivo ADP ribosylation was decreased in both organs after both
      administration routes, although to different degrees (higher in the liver after
      intravenous and in the brain after intracerebroventricular administration),
      suggesting that NO had been produced in the periphery and in the brain after both
      routes of LPS administration, despite the fact that no LPS is expected to reach
      the brain after peripheral low-dose injection. Our data thus demonstrate a cross
      talk between periphery and brain in the regulation of NO by LPS. Additionally,
      the possibility of iNOS-independent NO synthesis stimulated by LPS is implied by
      the discrepancy between the amount of local NO production suggested by ADP
      ribosylation and the iNOS mRNA levels.

PMID- 9266550
TI  - Batten disease in the west of Scotland 1974-1995 including five cases of the
      juvenile form with granular osmiophilic deposits.
AB  - We report on 12 children with neuronal ceroid lipofuscinosis (NCL) diagnosed
      between 1974-1995 in the West of Scotland. Diagnosis was made on the basis of
      clinical, electrophysiological, radiological and pathological examination
      including electron microscopy (EM) in all cases. Incidence was calculated on the
      basis of the year of diagnosis and the live birth rate. Six cases were infantile
      and 6 juvenile NCL derived from a total of 10 families. No cases of late
      infantile or early juvenile NCL were identified. All cases were typical in
      clinical description. Cumulative incidence was 1.61/100,000 live births (0.87 and
      0.73/100,000 live births for juvenile and infantile NCL respectively). There was
      significant delay in diagnosis of the juvenile form of NCL. EM findings were
      unusual in the juvenile group in that 5 of 6 cases exhibited granular osmiophilic
      deposits (GROD) rather than typical fingerprint inclusion bodies. Four of these 5
      cases also failed to show vacuolation of lymphocytes. Thus, in the West of
      Scotland, the distribution of NCL cases by type and by EM findings is unusual,
      and suggests a distinct genetic variant of juvenile NCL, possibly allelic to
      infantile NCL.

PMID- 9266549
TI  - Effect of acute dietary restriction on the colonization of MADB106 tumor cells in
      the rat.
AB  - The effects of acute food restriction (i.e. 24-72 h) on (1) the colonization of
      MADB106 tumor cells; (2) the response of specific T cell subsets in peripheral
      blood (i.e. CD4+ and CD8+ cells), and (3) natural killer cell activity (NKCA) in
      the spleen were studied in the Fischer 344 rat. Previous studies have
      demonstrated that the spread of this tumor cell is enhanced by exposure to an
      acute stressor within 24 h of tumor inoculation. Consistent with these reports,
      72-hour food restricton after tumor inoculation enhanced colonization of tumor
      cells to the lungs when assessed 4 weeks after inoculation. Food restriction was
      found to markedly influence the percentage of T cell subsets (i.e. CD4+ and CD8+
      cells) and NKCA in the early (24-72 h) postinoculation stage. At 72 h after
      inoculation, food restriction was associated with a significant reduction in the
      percentage of CD4+ cells in tumor- or saline-inoculated animals. The percentage
      of CD8+ cells was significantly increased at 24 and 72 h after tumor inoculation
      in ad libitum, but not in food-deprived animals. NKCA at 72 h was significantly
      reduced in saline-treated food-deprived animals compared to animals fed ad
      libitum. Given that glucocorticoids are typically increased during acute food
      deprivation and that glucocorticoids are in some instances associated with
      depressed NKCA, the present study investigated whether there was a relationship
      between plasma glucocorticoid levels (i.e. corticosterone) and NKCA; however, no
      significant relationship was found. In conclusion, the present findings
      demonstrate that 72-hour food deprivation is associated with enhancement of tumor
      metastasis. This outcome is mediated, at least in part, by the modulatory effect
      of the physiological response to acute food restriction upon the distribution of
      circulating T cells and NKCA in the spleen during the early (24-72 h)
      postinoculation phase.

PMID- 9266551
TI  - Evidence of brain ischemia in early neonatal sudden death syndrome.
AB  - Ten early neonatal sudden death victims (ENSD) were selected for
      neuropathological and immunohistochemical examinations. The gestational ages of
      the victims ranged from 36 to 42 weeks, and the postnatal ages from 8 hours to 10
      days of life. In 6 of 10 patients, softening with rarefaction was observed in the
      subcortical or intermediate white matter, which was associated with minimal
      astrogliosis in the whole white matter. In 7 of the 10 ENSD victims, the number
      of GFAP-positive glia was significantly greater in both the deep and subcortical
      white matter than in controls. The brainstem showed mild gliosis in the reticular
      formation and vagal nuclei of the medulla oblongata in 8 of the 10 ENSD victims.
      In 8 of the 10 ENSD victims, the number of GFAP-positive astrocytes was greater
      in both the dorsal vagal nucleus and the reticular formation of the medulla
      oblongata than in controls. The high incidence of leukomalacia and astrogliosis
      in the cerebral white matter and brainstem suggests the presence of brain
      ischemic insults before death, which may be prenatal in some cases.

PMID- 9266552
TI  - Cerebral magnetic resonance imaging and mental and motor function of very low
      birth weight children at six years of age.
AB  - In this follow-up study, 20 of a geographically based year cohort of 31 surviving
      non-disabled VLBW (birthweight < 1500 g) children were examined at six years of
      age. The aim of the study was to relate cerebral MRI findings to neuro
      development in these non-disabled children at six years of age. All MRI scans
      were evaluated for myelination pattern, periventricular gliosis, ventricular
      dilation and cortical atrophy. The Peabody motor test and the Wechsler Preschool
      and Primary Scale of Intelligence (WPPSI) were used in the evaluation of motor,
      mental and perceptual function. A diagnosis of attention deficit disorder with
      hyperactivity was made based on the examiner's impression of the child during the
      examination and based on the parent's history. We found that ten (50%) of the
      children had periventricular gliosis, mainly in centrum semiovale (CS) (nine
      children) and in central occipital white matter (COW) (six children). Gliosis in
      CS was related to lower scores on the Peabody gross motor test for locomotion,
      indicating involvement of corticospinal tracts. Additional gliosis in COW was
      related to both fine motor and gross motor impairments. We speculate that this
      indicates damage to both motor and visual pathways, affecting eye-hand
      coordination and balance function. No relationship between MRI deviations at six
      years and mental function based on performance, verbal and total IQ scores was
      found. However, there was a significant relationship between periventricular
      gliosis in COW and C5 and low scores on the WPPSI performance subtests: Picture
      completion test and Block design test. This may indicate visual and spatial
      perception problems, caused by damage to posterior visual pathways and occipito
      thalamic tracts dealing with visuo-motor integration.

PMID- 9266553
TI  - Visual function in full-term infants with hypoxic-ischaemic encephalopathy.
AB  - Thirty-one full term infants with hypoxic-ischaemic encephalopathy (HIE) were
      studied with a battery of tests designed to evaluate visual function in infancy
      and with serial MRI. Their age ranged between 5 and 31 months. The aim of the
      study was to evaluate whether the degree of HIE or the site and size of lesions
      on MRI could predict visual outcome. Twenty of the 31 infants studied showed
      abnormal results on at least one of the visual tests used. While visual function
      was generally normal in grade I HIE and severely impaired in grade III, visual
      outcome was variable in grade II. MRI findings were better predictors of visual
      impairment than the degree of HIE. Normal scans tended to be associated with
      normal visual function, irrespective of the severity of HIE. All but one of the
      infants with diffuse hemispheric involvement also showed multiple visual
      abnormalities. The concomitant involvement of basal ganglia was always associated
      with more severe visual outcome. These results suggest that infants with
      generalised lesions secondary to global insults are at high risk of severe visual
      impairment even in presence of normal acuity and require early assessment of
      various aspects of visual function.

PMID- 9266554
TI  - Sleep state, cardiorespiratory and electrocortical activity in infants with
      transposition of great vessels.
AB  - OBJECTIVES: Sleep states and physiological changes during sleep may be useful in
      assessing brain function. We hypothesized that infants with transposition of
      great vessels (TGV) exhibit recognizable states of sleep under conditions of
      isocapnic hypoxemia. Also, we speculated that early correction of hypoxemia may
      result in significant changes in the physiological characteristics of quiet and
      active sleep. METHODS: Six-hour continuous cardiorespiratory and electrocortical
      recordings were performed in five term infants with TGV, pre- and postoperatively
      along with simultaneous minute by minute behavioral sleep state assignment. Data
      were sorted for sleep states and percent sleep time for each state was computed.
      Measurements of state-dependent variables, i.e., heart rate (HR), heart rate
      variability (HRSD), respiratory frequency (f), variability in respiratory
      frequency (fSD), and spectral properties of the EEG during quiet and active sleep
      were compared for both pre- and postoperative periods. RESULTS: All infants
      showed significant differences in state-dependent variables between quiet and
      active sleep, both during preoperative (mean O2 saturation = 80.9 +/- 2.8) and
      postoperative (mean O2 saturation = 92.8 +/- 0.5) periods. As compared to
      preoperative period, postoperatively during quiet sleep, HR and HRSD were lower,
      and EEG power was greater; and during active sleep, HR, HRSD, and fSD decreased
      and EEG power increased. Also, in the postoperative period % quiet sleep
      increased and % active sleep decreased. CONCLUSIONS: Under conditions of
      isocapnic hypoxemia infants with TGV vessels exhibit clearly recognizable states
      of sleep. Correction of hypoxemia is associated with significant changes in state
      dependent variables both during quiet and active sleep.

PMID- 9266555
TI  - Mechanisms of central motor reorganization in pediatric hemiplegic patients.
AB  - Twenty hemiplegic patients were studied with transcranial magnetic stimulation
      (TMS). Motor evoked potentials (MEPs) of the biceps brachii (BB) and the abductor
      pollicis brevis muscles (APB) were recorded on both sides simultaneously. TMS was
      carried out with an 8-shaped coil over different scalp positions in the intact
      hemisphere. Bilateral MEPs of BB were elicited in patients with later childhood
      lesions as well as early lesion, but those of APB were only elicited in the
      latter (up to 2 years). In patients with prenatal or birth lesion on BB and in
      all patients on APB, cortical maps of MEP amplitude of paretic and non-paretic
      sides showed similar distributions. There were no remarkable differences in mean
      latency between both sides, and correlation coefficients of MEP amplitude between
      both sides were high in these patients. In patients with postnatal lesion on BB,
      MEP maps of both sides showed different distributions, ipsilateral MEP latencies
      were delayed and correlation coefficients were low. We suspect that ipsilateral
      MEPs after early lesion derive from axonal sprouting both in the proximal and the
      distal muscles. After postnatal lesion, other mechanisms of ipsilateral motor
      projection take place in the proximal muscles, but not in the distal ones.

PMID- 9266556
TI  - CRASH syndrome: mutations in L1CAM correlate with severity of the disease.
AB  - X-linked hydrocephalus, MASA syndrome and certain forms of X-linked spastic
      paraplegia and agenesis of corpus callosum are now known to be due to mutations
      in the gene for the neural cell adhesion molecule L1 (19, 30). As a result, these
      syndromes have recently been reclassified as CRASH syndrome, an acronym for
      Corpus callosum hypoplasia, Retardation, Adducted thumbs, Spasticity and
      Hydrocephalus (8). A comparison of existing case reports with molecular genetic
      analysis reveals a striking correlation between the type of mutation in the L1CAM
      gene and the severity of the disease. Mutations that produce truncations in the
      extracellular domain of the L1 protein are more likely to produce severe
      hydrocephalus, grave mental retardation or early death than point mutations in
      the extracellular domain or mutations affecting only the cytoplasmic domain of
      the protein. While less severe than extracellular truncations, point mutations in
      the extracellular domain do produce more severe neurologic problems than
      mutations in just the cytoplasmic domain.

PMID- 9266557
TI  - Is Rett syndrome caused by a triplet repeat expansion?
AB  - Rett syndrome is usually sporadic, but rare pedigrees with nonpenetrance in
      obligate carriers and possible anticipation suggest that it could be caused by a
      triplet repeat expansion (TRE). Rett probands and controls were systematically
      screened for expansions of any of the 10 possible triplet repeats by using a
      modified Repeat Expansion Detection (RED) assay that had been shown to detect
      expanded disease alleles in myotonic dystrophy and Huntington disease. No
      significant expansions were found in 26 sporadic and six familial Rett probands.
      Our results exclude the possibility that Rett syndrome is caused by a large TRE.
      We cannot exclude, however, causation by a small TRE that is masked by the
      background of longer polymorphic repeats in the normal population.

PMID- 9266558
TI  - Early onset of leptomeningeal cyst with severe brain herniation: report of two
      cases.
AB  - Leptomeningeal cyst as a rare complication of skull fracture in children is well
      documented. Most cases occur months or years after the original skull fracture,
      with characteristic roentgenogram findings. The authors report two cases of
      leptomeningeal cysts in children less than two years old. The association of
      hygroma, severe brain injury, increased ICP, and early development of
      leptomeningeal cyst are discussed. Both patients sustained parietal diastatic
      skull fracture and developed external brain herniation within 10 days after motor
      vehicle accidents. Clinically they presented with seizure, hemiparesis, and an
      enlarging subgaleal mass over the skull fracture. MRI demonstrated severe
      underlying brain contusion, hygroma around the fracture site, and brain
      herniation through the skull fracture. Surgical repair of dural laceration and
      cranioplasty produced good results. The development of hygroma and increased
      intracranial pressure might account for the early development of leptomeningeal
      cysts in these two cases.

PMID- 9266559
TI  - [Anatomical strategy of parasellar tumor surgery].

PMID- 9266560
TI  - [Shearing injuries of parasagittal white matter, corpus callosum and basal
      ganglia: possible radiological evidences of hemiplegia in diffuse axonal injury].
AB  - The relationship between spastic hemiplegia in diffuse axonal injury (DAI) and
      neuroradiological findings was studied in 100 cases. These cases were
      prospectively collected from the files of Automobile Insurance Rating
      Organization in Japan between 1993 from to 1996. Requirements for entry to this
      study were as follows: presence of initial unconsciousness after head injury
      without any lucid interval. Existence of CT scan or MRI film obtained within 12
      hours of injury showing no significant mass effects, as well as follow-up CT scan
      or MRI film obtained more than 3 months after the injury. Psychosocial outcome
      was described both by the medical professional and the caregiver. The hemiplegia
      was rated severe, mild, or none. The outcome and diffuse ventriculomegaly were
      classified as reported by the authors previously. Spastic hemiplegia or
      quadriplegia was documented in the chronic stage in 63 cases, including 53 severe
      cases with difficulty in walking and 10 mild cases with only pyramidal signs
      detected. Chi-square analysis showed significant correlation between hemiplegia
      and the DAI outcome level or ventriculomegaly rating. Focal brain contusion was
      noticed in 33 cases, but did not correlate with the hemiplegia at all.
      Radiological findings included 25 cases of parasagittal white matter injury
      (gliding contusion), 20 cases of callosal injury, 19 cases of basal ganglionic
      region injury, 5 cases of brain-stem injury, and 3 cases of cerebellar injury.
      Chi-square analyses of hemiplegia and contralateral presence of these injuries
      were significant in the former three types of injury. Presence of at least one of
      these 3 lesions was defined as GCB injury. There were altogether 46 GCB injury
      cases which were significantly correlated with contralateral hemiplegia by chi
      square analysis and by Spearman rank analysis. Partial correlation analysis with
      hemiplegia as the target variable indicated highly significant correlation only
      with GCB injury and outcome level. In conclusion, spastic hemiplegia in DAI is a
      manifestation of primary shear injury. Neuroradiological findings of GCB injury
      were statistically able to be significantly correlated with the presence of
      hemiplegia, and suggested pyramidal tract injury either at the corona radiata or
      the internal capsule level.

PMID- 9266561
TI  - [Postoperative three-dimensional CT angiography (3D-CTA) in evaluation of
      proximal clipping for ruptured vertebral aneurysms].
AB  - At present, intra-arterial angiography remains the gold standard for most
      cerebrovascular problems. Recently, three-dimensional computed tomographic
      angiography (3D-CTA) has been reported as a screening method for the diagnosis of
      cerebrovascular disease. This imaging modality uses the information obtained on a
      contrast-enhanced CT scan to generate three-dimensional images of the
      cerebrovascular system. We performed 3D-CTA in the preoperative and postoperative
      evaluation of patients undergoing proximal clipping of ruptured vertebral artery
      aneurysms in addition to conventional cerebral angiography. In this study, the
      value of 3D-CTA after proximal clipping of ruptured vertebral artery aneurysm was
      evaluated retrospectively. Six patients were examined with a spinal CT (HITACHI
      CT-W 3000) after intravenous bolus injection of 100 ml contrast material
      (Iohexhol 300 mgI/ml) at the rate of 2 ml/s with a 25 second pre-scanning delay.
      The images of 3D-CTA were reconstructed using a new 3D-volume-render (Voxel
      Transmission) technique. The ages of the six patients ranged from 33 to 61 years
      and five cases were males and one case was female. Only one patient had a
      saccular aneurysm and the other five had fusiform aneurysms. Two patients
      underwent emergency operations within 4 days, and the other four had delayed
      operations. The outcome was good recovery in five cases and severe disability in
      one case. Postoperative conventional cerebral angiography demonstrated no
      delineation of the aneurysms in five cases. These results correspond well to
      postoperative 3D-CTA. Postoperative conventional cerebral angiography could not
      be performed in only one patient, but the aneurysm was visualized on the third
      postoperative 3D-CTA. Proximal clipping is still one of the therapeutic options
      for ruptured vertebral aneurysms, but some reports emphasized the possibility of
      rebleeding after proximal clipping of vertebral artery aneurysms. The rebleeding
      occurred within 1 week after proximal clipping in 6 of 9 cases (66.7%), and the
      prognoses were extremely poor. Therefore, in patients selected for proximal
      clipping, it is necessary to undertake postoperative evaluation of the aneurysm
      within one week after proximal clipping. 3D-CTA is minimally invasive and can be
      easily performed repeatedly, even if the patients are in a poor condition. In
      conclusion, 3D-CTA is very useful especially for evaluation of ruptured vertebral
      artery aneurysms following proximal clipping.

PMID- 9266562
TI  - [Histological study of operated cases of chronic subdural hematoma in adults:
      relationship between dura mater and outer membrane].
AB  - In 31 consecutive operated cases of chronic subdural hematoma (CSH) in adults, a
      histological study of the outer membrane and the dura mater was reported. Only 3
      cases had vascular connections between the dura mater and the outer membrane. The
      vessels from (or to) the dura mater entered into the sinusoidal channel of the
      outer membrane. Dura mater always showed normal findings and was distinctly
      separated from the outer membrane, except for vascular connections. Because of
      this, they were regarded as different tissues. Hemorrhages in and out of the
      hematoma cavity of the outer membrane were seen in all 12 cases and seemed to be
      a reason for enlargement of CSH. There were 16 cases of eosinophilic infiltration
      in the outer membrane. No positive reaction was seen to estrogen receptor
      staining of either the dura mater or the outer membrane.

PMID- 9266563
TI  - [Analysis of factors related to microemboli in cases with internal carotid artery
      stenosis].
AB  - Transcranial Doppler ultrasound (TCD) has been used to detect microemboli in
      cases with extracranial internal carotid artery stenosis. However, the mechanism
      causing microemboli has remained unclear. The purpose of this study is to clarify
      clinical characteristics and circumstances associated with the genesis of TCD
      detected microemboli. Ninety-one cases with more than 30% stenosis of the
      internal carotid arteries were studied. TCD monitoring was carried out for an
      hour at the ipsilateral middle cerebral artery of each case using a 2-MHz pulse
      wave transcranial Doppler device, and high intensity transient signals were
      counted as microemboli. Digital subtraction angiography, magnetic resonance
      imaging (MRI) and single photon emission computed tomography (SPECT) were also
      performed in all cases. Microemboli were detected in 30 of 91 cases. Microemboli
      were significantly well detected in cases with a history of ischemic event and/or
      cerebral infarction recognized by MRI. Detection of microemboli had no relation
      to sex, age or clinical risk factors (hypertension, hypercholesterolemia,
      diabetes mellitus and smoke habituation). In contrast, detection of microemboli
      was significantly related to decrease in cerebral blood flow recognized by SPECT,
      severity of stenosis and wall irregularity of lesion recognized by angiography.
      Microemboli can be found in a significantly high percentage of these clinical
      conditions, which may be risk factors for embolic stroke caused by extracranial
      internal carotid artery stenosis.

PMID- 9266564
TI  - [Rapidly enlarging supratentorial ependymoma in a child presenting initially with
      a small calcified lesion: case report].
AB  - The authors report an unusual case of a 11-year-old boy whose supratentorial
      ependymoma showed rapid growth. He had had generalized convulsive seizures when
      he was 9 years old. On an initial CT scan a small calcified lesion was identified
      adjacent to the right sensorimotor cortex. Repeated CT scans showed no interval
      change in the size of the tumor for 16 months. Then, he suffered an acute onset
      of left hemiparesis. The neuroimaging studies demonstrated a huge tumor with a
      large cyst in the right parietal region which had not been observed on CT scan 7
      months before. Total removal of the tumor was performed and the histopathological
      diagnosis was ependymoma with no evidence of malignancy. However, MIB-1 staining
      of the specimen revealed a high index of 1 proliferative potential up to 25% in
      some area. The high score of MIB-1 staining correlated well with the rapid
      clinical course of this histologically benign ependymoma. The small calcified
      lesion demonstrated on the initial CT scan in this case is considered to have
      been a low grade ependymoma and to have abruptly transformed into a higher grade,
      one resulting in rapid enlargement. The authors stress that small intracranial
      calcified lesions should be carefully followed up by repeated neuroimaging
      studies at short intervals.

PMID- 9266565
TI  - [Arachnoid cyst of the middle cranial fossa with extraocular muscle paresis: case
      report].
AB  - Arachnoid cysts in the middle cranial fossa usually present with skull deformity,
      intracranial hypertension, epilepsy, focal symptoms and delayed mental
      development. Some cases, however, have neither symptoms nor signs. We have
      encountered a patient with an arachnoid cyst of the middle cranial fossa with
      extraocular muscle paresis and who was treated with cyst wall fenestration with
      good results. An 11-year-old boy presenting with double vision was diagnosed as
      having an arachnoid cyst in the middle cranial fossa with extraocular muscle
      paresis. He had no signs of increased intracranial pressure. This patient
      underwent a cyst membranectomy. Postoperatively this symptom rapidly subsided.
      Double vision disappeared two months postoperatively. To our knowledge, if those
      cases associated with increased intracranial pressure signs are excluded, this is
      the first case reported so far of a middle cranial fossa arachnoid cyst with
      extraocular muscle paresis. This report illustrates that extraocular muscle
      paresis can be caused by an arachnoid cyst in the middle cranial fossa and that
      knowledge of this could be helpful in its early diagnosis and treatment.

PMID- 9266566
TI  - [A case of spontaneous middle cerebral artery occlusion associated with a
      cerebral aneurysm angiographically disappearing after STA-MCA anastomosis].
AB  - We report a case of a rapidly growing cerebral aneurysm in the basal abnormal
      vascular network associated with spontaneous middle cerebral artery (MCA)
      occlusion. The aneurysm disappeared spontaneously shortly after performing STA
      MCA anastomosis. A 54-year-old female was admitted to our hospital because of
      repeated attacks of right hemisensory disturbance and dysarthria. CT scan and MRI
      images showed the infarcted focus in the left parieto-occipital lobe. Bilateral
      MCAs were undetectable on MRI images. Cerebral angiography revealed that the
      bilateral MCAs were occluded in their proximal origin with basal abnormal
      vascular networks. The distal MCA branches were perfused via the vascular
      networks. A small aneurysm was detected in the distal portion of the left
      Heubner's artery. There were no abnormalities in the bilateral internal carotid
      arteries, the anterior cerebral arteries, and the basilar artery. The follow-up
      angiography performed 29 days after admission revealed a growing aneurysm with a
      diameter of 3 mm in the distal enhanced lesion consistent with the aneurysm
      observed in the angiography. An STA-MCA anastomosis was performed for improvement
      of cerebral misery perfusion. Single photon emission tomography (SPECT) performed
      9 days after the bypass operation revealed improvement of cerebral blood flow in
      the left parieto-occipital lobe, and her TIA attacks disappeared. The aneurysm
      was undetected in the cerebral angiography performed 24 days after the bypass
      operation. Spontaneous MCA occlusion is a rare condition of chronic
      cerebrovascular occlusive diseases. Diagnostic criteria of the disease includes
      the MCA occlusions or stenosis with basal abnormal vascular networks. Usually the
      phenomenon is seen unilaterally, which differs from moyamoya disease. Diagnosis
      must exclude diseases caused by the etiologies such as those of arteriosclerotic
      origin. There have been 24 reported cases of spontaneous MCA occlusion including
      our case. Among them, 9 cases presented cerebral aneurysm located in abnormal
      vascular networks, and all the reported cases presented cerebral hemorrhage at
      their onset. The abnormal basal vascular network may be developed as collateral
      vessels to supply blood to the ischemic regions in this disease. An increased
      hemodynamic stress in the abnormal basal vascular network may produce a true
      aneurysm in the distal portion of the perforating arteries. STA-MCA anastomosis
      reduced the TIA attacks, but also decreased the hemodynamic stress on the
      abnormal basal vascular network and resulted in reduction in size or thrombosis
      of the aneurysm. STA-MCA anastomosis can be considered effective to treat
      cerebral aneurysms located in vessels with increased hemodynamic stress.

PMID- 9266568
TI  - [Transarterial embolization of a vein of Galen aneurysm: a case report].
AB  - This report describes a case of a vein of Galen aneurysm. A 6-month-old baby with
      a slight head injury was referred to our hospital. CT scans and MR images
      demonstrated a vein of Galen aneurysm. Left carotid angiogram showed a vein of
      Galen aneurysm with a large feeding artery from the posterior cerebral artery.
      Transarterial embolization was performed using Galen coils and Interlocking
      Detachable Coils. Angiograms after the second embolization revealed complete
      occlusion of the aneurysm and postoperative course was uneventful.

PMID- 9266567
TI  - [A case of cavernous dural arteriovenous fistula resulting in intracerebral
      extravasation during transvenous embolization].
AB  - Cortical venous drainage has been described as one of the major risk factors for
      dural arteriovenous fistula, which may induce venous hypertension leading to
      venous ischemia or intracerebral hemorrhage. However, it is rather rare to
      observe cortical venous drainage manifesting in this way in the cavernous sinus
      region. We report a case of a 55-year-old gentleman with a right cavernous dural
      arteriovenous fistula, presenting with conjunctival chemosis, exophthalmus and
      ocular hypertension on the affected side. Magnetic resonance imaging showed a
      small intracerebral hemorrhage in the right frontal lobe. Cerebral angiography
      revealed a dural arteriovenous fistula in the right cavernous sinus draining into
      the right olfactory vein via the uncal vein, as well as into the superior and
      inferior ophthalmic veins. This unusual cortical venous reflux was thought to be
      consistent with the intracerebral hemorrhage found on the magnetic resonance
      imaging. The patient underwent transvenous embolization for the dural
      arteriovenous fistula using an inferior petrosal catheterization into the uncal
      vein was difficult, and the cortical venous reflux through the vein seemed to be
      slight. However, extravasation of the contrast material occurred in the right
      frontal lobe after obliteration of the ophthalmic veins during the procedure. The
      cause of the extravasation was suspected to be the same olfactory vein that had
      been involved in the previous intracerebral hemorrhage. The obliteration of the
      dural fistula was continued rapidly, and the fistula disappeared after the
      embolization. Neurologically, the patient had no noticeable troubles, except for
      a mild headache. The pretreatment symptoms were alleviated within several days,
      and the patient was discharged in a week. We emphasize the following points from
      this rare case in order to facilitate a safer procedure during transvenous
      embolization for cavernous dural arteriovenous fistula. It is important to
      obliterate the cortical venous drainage as early as possible, even if the reflux
      is small or the catheterization is difficult. Repeated, careful sinography is
      useful for the evaluation of the drainage pattern at certain stages during the
      transvenous embolization procedure.

PMID- 9266569
TI  - [A case of intradural xanthogranuloma in the upper cervical spine].
AB  - An 18-year-old female patient suffered from posterior neck pain and gait
      disturbance. The neurological examination revealed left hemiparesis, general
      hyperreflexia and hypoalgesia on the right neck and upper limb, and left trunk
      and lower limb. MRI showed a large mass lesion in the right side of the spinal
      canal at the level of the C1 cervical spine, which was obviously compressing the
      spinal cord. An operation was performed through a right suboccipital craniectomy
      and right hemilaminectomy of the first vertebra. Though the mass lesion in the
      subarachnoid space compressed the spinal cord, it adhered neither to the spinal
      cord nor to the nerve roots. However, as it clearly adhered to the dura mater,
      the attachment site was also completely removed. In the pathological examination,
      lymphocyte, foamed macrophage and the giant cell of Touton type were shown. The
      immunohistochemical study with CD68 (Kp1) was positive, but it was negative for
      the lysozyme, neuron specific enolase and S-100 protein. The diagnosis was
      xanthogranuloma. The patient recovered completely after the operation. This is a
      rare case of juvenile type xanthogranuloma. This lesion in the spinal canal has
      usually its onset in the adult age.

PMID- 9266570
TI  - [A surgery for an acute case of a ruptured aneurysm associated with idiopathic
      thrombocytopenic purpura: a case report].
AB  - A surgery for an case acute of a ruptured aneurysm with idiopathic
      thrombocytopenic purpura (ITP) is very rare. We encountered a case of a ruptured
      basilar artery (BA) superior cerebellar artery (SCA) aneurysm associated with
      ITP. A successful operation was carried out while the patient was in the acute
      stage. The patient was a 63-year-old female. She has been suffering from ITP for
      two years, when she experienced a sudden severe headache and vomitting on May 5,
      1995. She was referred to our hospital as a case of subarachnoid hemorrhage
      estimated to be in group 2 according to the Fisher grade. Her neurological
      condition caused by the subarachnoid hemorrhage was grade 2 according to Hunt &
      Kosnik classification, and she was classified according to WFNS as grade 1. The
      number of platelets was, however, 2.3 x 10(4)/mm3 on admission. Cerebral
      angiography showed the aneurysm at the bifurcation of BA and SCA. The
      administration of platelet transfusion, betamethasone and gamma-globulin induced
      an increase of the number of platelets to 8.7 x 10(4) mm3 just before the
      operation. Neck clipping for the aneurysm was performed using platelet
      transfusion via the right pterional approach 25 hours after the onset. No
      tendency to bleed was recognized during the operation. The number of platelets
      was kept constantly at the level between 16.9 x 10(4)/mm3 and 22.0 x 10(4)/mm3
      during the postoperative course with the administration of betamethasone. The
      postoperative course was good with no manifestations of delayed ischemic
      neurological deficits.

PMID- 9266571
TI  - [Rupture of previously documented asymptomatic saccular intracranial aneurysms].
AB  - The authors report four cases of patients with documented asymptomatic intact
      aneurysms that subsequently ruptured. Case 1 involves a 64-year-old woman who had
      two unruptured aneurysms, i.e., an anterior communicating artery aneurysm and a
      posterior inferior cerebellar aneurysm, both were discovered during evaluation of
      cerebral ischemic symptoms. At that time, only the posterior inferior cerebellar
      aneurysm was clipped. Seven years later, the patient bled fatally from a 5-mm
      untreated anterior communicating artery aneurysm that had measured approximately
      3 mm on an angiogram obtained 7 years earlier. Case 2 is that of a 50-year-old
      woman who bled from an anterior communicating artery aneurysm that had been
      discovered 6 years earlier when she suffered subarachnoid hemorrhage (SAH) from a
      left middle cerebral artery aneurysm. At that time, she had refused surgery for
      the anterior communicating artery aneurysm. She recovered well from the second
      SAH. Case 3 is that of a 74-year-old woman who bled from a left paraclinoid
      internal carotid artery aneurysm that had been discovered incidentally 3 years
      earlier during evaluation of vertigo. She had not agreed to have a clipping at
      that time the aneurysm was first discovered because of her age and the difficult
      location of the aneurysm. She eventually made an uneventful recovery. In the
      fourth case, during evaluation of cerebral ischemic symptoms, a 59-year-old man
      was discovered to have a large basilar bifurcation aneurysm. He underwent a
      craniotomy for clipping of the aneurysm. The aneurysm, however, was unclippable
      and was instead coated with Bemsheet. Four months later, the patient bled from
      the aneurysm and entered a vegetative state. The indications for surgery on
      unruptured asymptomatic cerebral aneurysms are still unclear. The cases reported
      herein show that asymptomatic aneurysms, especially anterior communicating
      aneurysms and aneurysms once exposed surgically, do carry a certain risk for
      future hemorrhage and should not be dismissed as innocuous. Neurosurgeons have
      recognized the importance of considering life expectancy in managing patients
      with asymptomatic, unruptured, intracranial aneurysms. With the rapid aging of
      the population, withholding aneurysm surgery merely because a patient is elderly
      may not necessarily be the most appropriate decision.

PMID- 9266572
TI  - [True "PICA communicating artery" aneurysm: a case report].
AB  - We present an unusual case of an aneurysm of the distal posterior inferior
      cerebellar artery (PICA). A 51-year-old female presented a subarachnoid
      hemorrhage with mild consciousness disturbance on August 6, 1992. Computed
      tomography (CT) on admission showed subarachnoid hemorrhage with thick hematoma
      in the cisterna magna and intraventricular hematoma in the 4th, 3rd and both
      lateral ventricles. The angiogram on admission revealed no definite vascular
      anomalies. Repeated angiograms on the 11th day after onset showed an aneurysm on
      anastomotic branch between the bilateral distal PICAs. The aneurysm was clipped
      successfully through a suboccipital craniectomy 14 days after the onset. In the
      literature reviewed, only one such aneurysm, located at an anastomotic vessel of
      the bilateral PICAs, has been reported by Hlavin et al in 1991. They reported
      that the aneurysm was associated with a unilateral PICA that supplied both
      cerebellar hemispheres and arose from an anastomotic vessel in the contralateral
      circulation. They called the aneurysm as "a PICA communicating artery" aneurysm.
      We assume that this "PICA communicating artery" is a remnant of a primitive
      lateral vertebrobasilar anastomosis, which appears in the embryo at the 9 mm
      stage. It is suggested that the pathogenesis may be not only the hemodynamic
      factor but also a congenital anomaly.

PMID- 9266573
TI  - Off-label prescribing during pregnancy.
AB  - Obstetricians frequently prescribe drugs for indications other than those on the
      product label. Reasons for such off-label use during pregnancy include prevention
      of repetitive abortion, inhibition of premature labor, reduction of fetal or
      neonatal infection, reduction in development of preeclampsia and its
      complications, and ripening of the cervix or induction of labor. A physician has
      a legal right to prescribe for off-label indications despite regulatory,
      manufacturer, and cost constraints. Such prescribing habits would not be
      considered experimental if based on sound scientific evidence. Adequate and well
      controlled studies are difficult, however, to perform during pregnancy. Evidence
      of widespread use and support from another qualified clinician are methods of
      justifying off-label prescribing. Each patient is entitled to know why she and
      her fetus would benefit from the treatment and whether any unnecessary risk is
      anticipated. Legible documentation of these discussions in the medical records is
      important.

PMID- 9266574
TI  - Vitamin and mineral supplement prior to and during pregnancy.
AB  - Vitamin and mineral supplementation during pregnancy is a common practice in the
      United States, but is often unnecessary. An assessment of dietary practices is
      recommended for all women to evaluate the need for improved diet or vitamin and
      mineral supplementation. Most women do not receive enough folic acid from dietary
      sources and should take a folic acid supplement in the preconception period to
      minimize their risk of neural tube defect. Iron supplementation is recommended in
      the second and third trimester. A multivitamin and mineral supplement is
      recommended during pregnancy for women who do not ordinarily consume an adequate
      diet and for women in high-risk categories, such as multifetal gestation, heavy
      cigarette smokers, and alcohol and drug abusers.

PMID- 9266575
TI  - Current concepts of anticoagulant therapy in pregnancy.
AB  - The optimal use of anticoagulants during pregnancy will continue to be
      controversial until appropriate randomized controlled and prospective trials with
      adequate sample sizes are completed. The relative low frequency of thromboembolic
      events, the concerns about maternal and fetal safety of both treatment and
      withholding treatment, and the reservations about prospectively enrolling
      pregnant women in treatment trials has sadly dissuaded the appropriate study of
      this life-threatening condition. North American trials that enroll pregnant women
      to evaluate the efficacy of LMWH are of preeminent importance owing to their
      superior bioavailability, ease in dosing, longer half-life, and side effect
      profile. Similarly, trials evaluating the optimal management of women of
      childbearing age with valvular disease are critical to reduce the considerable
      maternal and fetal morbidity and mortality associated with these pregnancies.
      Such definitive studies will need to be multicenter in design and it is hoped
      that the National Institutes of Health initiative to enroll pregnant women in
      clinical trials will at last be realized in the near future.

PMID- 9266576
TI  - Maternal and fetal implications of anticonvulsive therapy during pregnancy.
AB  - A team approach with close communication among the obstetrician, neurologist,
      pediatrician, and patient will result in an uneventful pregnancy in most
      epileptic women. Women should be counseled regarding the greater than 90%
      likelihood of a favorable outcome. Maternal and neonatal outcome can be optimized
      by carefully evaluating the clinical necessity of anticonvulsant medications
      preconceptionally. One can then prescribe an appropriate choice based on seizure
      type and history of response, with a goal of achieving monotherapy at the lowest
      effective dose. Nonpharmacologic intervention, such as avoiding high levels of
      stress and sleep deprivation, will also help the patient to remain seizure-free
      during the pregnancy. In addition, folic acid and vitamin K can help optimize
      neonatal outcome. In short, most epileptic women will experience a normal
      pregnancy, labor, and delivery of a healthy baby and can breastfeed if desired.
      Although the incidence of congenital malformations with any anticonvulsant is
      increased, the actual incidence remains relatively low. Despite the shortcomings
      and risks of anticonvulsants, adequate therapy is clearly preferable to
      uncontrolled seizure activity. Women should be encouraged to optimize their
      anticonvulsive therapy prior to pregnancy, usually resulting in adequate therapy
      throughout the pregnancy and postpartum, with a happy and healthy outcome for
      mother and infant.

PMID- 9266577
TI  - Anxiety and depression. Diagnosis and treatment during pregnancy.
AB  - Anxiety and depression are common disorders that the obstetrician-gynecologist
      frequently encounters, and they often require consultation with mental health
      care professionals. Pregnancy offers an unusual challenge because many of the
      decisions made about the safety of certain drugs are educated guesses. Common
      sense dictates that no drug should be used unless a serious threat to the mother
      exists such as suicide. Preconceptional counseling and early referral to and from
      colleagues in mental health should help the obstetrician guide mother and fetus
      to a successful pregnancy outcome.

PMID- 9266578
TI  - Pharmacologic therapy of asthma during pregnancy.
AB  - Asthma is a common, potentially serious medical complication during pregnancy.
      Optimal clinical and pharmacologic management is necessary to mitigate maternal
      and fetal complications. Mild asthma may be managed in most cases with inhaled
      beta 2-mimetics. Anti-inflammatory therapy is recommended for the treatment of
      moderate and severe asthma. Based on limited human experience, beclomethasone is
      currently the recommended inhaled corticosteroid during pregnancy. However, other
      inhaled corticosteroids may have advantages compared to beclomethasone because of
      reduced systemic absorption, which may adversely affect intrauterine growth.
      Based upon theoretic considerations, theophylline is now considered a secondary
      therapy, but data demonstrating the superiority of inhaled corticosteroids versus
      theophylline during pregnancy are lacking.

PMID- 9266579
TI  - Treatment of thyroid disease in pregnancy.
AB  - With appropriate therapy, complications related to thyroid disease in pregnancy
      can be minimized. Although the diagnosis of thyroid endocrinopathy may be
      difficult in pregnancy, few therapies are contra-indicated. Because medications
      may cross the placenta, however, clinicians need always to be mindful of
      potential fetal effects and should work to use the minimal dose necessary to
      achieve maternal euthyroidism. Thyroid function tests, in particular free T4 and
      TSH, remain good measures of thyroid function and therapy in pregnancy.

PMID- 9266580
TI  - The use of chemotherapeutic agents during pregnancy.
AB  - The information available concerning the effects of chemotherapy administered
      during pregnancy is limited and consists of case reports and small series. A
      registry has been established at the National Cancer Institute, but there are
      currently only several hundred cases of neonates exposed to chemotherapy
      registered. All clinicians who care for women receiving chemotherapy during
      pregnancy should report those experiences to the National Cancer Institute to
      increase the data base. When chemotherapy is used during the embryogenesis period
      in the first trimester there is an increased rate of spontaneous abortion and
      major birth defects. The most toxic chemotherapeutic agents administered during
      pregnancy are methotrexate and aminopterin and should be avoided when possible,
      particularly during the first trimester. Pregnancy-related physiologic changes
      should be kept in mind when dosing and administering cytotoxic chemotherapy. The
      risk of fetal malformation when chemotherapy is administered during the second
      and third trimesters is probably not greater than background rate, but there may
      be a greater risk of stillbirth, fetal growth restriction, premature birth, and
      maternal and fetal myelosuppression. Breastfeeding should be avoided in women
      receiving chemotherapy.

PMID- 9266581
TI  - Immunosuppressive drugs and pregnancy.
AB  - Immunosuppressive therapy is a common practice in modern medicine. Typical uses
      of immunosuppressive drugs during pregnancy include the treatment of rheumatic
      diseases and transplant recipients. The purpose of this article is to assess and
      summarize current knowledge regarding the use of immunosuppressive drugs in
      pregnancy, focusing primarily on their effects on the mother and fetus.

PMID- 9266582
TI  - Antibiotic use in pregnancy.
AB  - With a few notable exceptions, most antibiotics can be used with relative safety
      during pregnancy. Moreover, none of the antibiotics to date has been shown to be
      teratogenic, although tetracycline may cause yellow-brown discoloration of the
      deciduous teeth (a fetal effect). Thus, antibiotics should not be withheld from
      the pregnant woman, especially when indicated for serious, life-threatening
      infections.

PMID- 9266583
TI  - Sexually transmitted diseases in pregnancy.
AB  - Sexually transmitted diseases are common complications of pregnancy and may have
      significant maternal/fetal effects. Knowledge of the symptoms and physical
      examination features, methods of diagnosis, indications for screening, and
      appropriate treatment options are essential for obstetric/gynecologic health care
      providers.

PMID- 9266584
TI  - Antiretroviral therapy during pregnancy. Beyond AZT (ZDV).
AB  - Although zidovudine (ZDV) monotherapy remains the standard for the prevention of
      mother-to-child transmission, it may now be inadequate therapy for treatment of
      the mother. The safety and efficacy of the newer therapeutic agents have yet to
      be established during pregnancy; however, the need to maintain maternal health
      mandates that clinicians understand the benefits and limitations of
      antiretroviral therapy beyond ZDV.

PMID- 9266585
TI  - The maternal and fetal effects of tuberculosis therapy.
AB  - Tuberculosis can cause significant morbidity in the pregnant woman, fetus, and
      members of the community. The first-line agents suggested by the CDC for use
      during pregnancy (isoniazid, rifampin, and ethambutol) seem to have minimal risk
      of induced congenital anomalies. Maternal morbidity associated with therapy does
      not seem increased above rates observed in the nonpregnant population. Education
      of the patient concerning the potential adverse side effects may decrease
      maternal morbidity. Therapy should be started as soon as the diagnosis of
      tuberculosis is confirmed (or when suspected in the HIV-infected woman) or after
      the first trimester in women younger than 35-years-old with recent TB tine test
      conversion. Monitoring for medication compliance during pregnancy is important to
      provide effective therapy and to decrease the development of resistant organisms.

PMID- 9266586
TI  - Drug therapy in the nursing mother.
AB  - The benefits of breast-feeding on newborn and infant health and for the maternal
      infant relationship are well established. It is a failing of health care
      providers that breast-feeding is too frequently interrupted because of unfounded
      concerns over the potential adverse effects of concurrent drug therapy in the
      nursing mother. An overwhelming minority of medications are contraindicated
      during lactation, while the vast majority are considered either safe to use or
      the risk versus benefit considerations clearly favor use with continuation of
      breast-feeding. For those drugs that may pose a potential concern to the newborn,
      there are practical suggestions and precautions that can be taken to minimize
      risk. These include such interventions as selection of alternative effective drug
      regimens with safer profiles in breast-feeding, timing of drug dosing to minimize
      accumulation in the breast milk, surveillance for newborn or infant
      symptomatology that may be a sign of toxicity, or even the determination of drug
      levels in the infant's circulation. With a commitment to the advantages of breast
      feeding and the information contained both herein and elsewhere regarding the
      interaction of medical therapy, pharmacology, and lactation, it is hoped that the
      health care provider will be empowered both to encourage and counsel more
      effectively the parturient who wishes to breast-feed but is concerned about
      ongoing drug therapy during lactation.

PMID- 9266587
TI  - Retrometabolic approaches for drug design and targeting.
AB  - Retrometabolic drug design approaches incorporate targeting and metabolic
      considerations into the drug design process and represent a novel, systematic
      methodology for the design of safe, localized compounds. Two major design
      concepts aimed to increase the therapeutic index (the activity/toxicity ratio) of
      drugs were developed. Chemical delivery systems (CDS) are primarily used to allow
      targeting of the active biological molecules to specific target sites or organs
      based on predictable enzymatic activation. Brain-targeted delivery of different
      agents like estradiol or AZT was successfully achieved, and recent progresses
      include delivery of peptides using a complex strategy designated as molecular
      packaging. Sequential site- and stereospecific enzymatic activation of
      oxime/alkoxime precursors of beta-adrenergic antagonists allows their eye
      targeted delivery. Soft drug approaches are used to design new drugs by building
      in the molecule, in addition to the activity, the most desired way in which the
      molecule is to be deactivated and detoxified subsequent to exerting its
      biological effects. Many examples are available to illustrate soft drug design,
      e.g., soft anticholinergics, soft b-blockers, soft antiinflammatory steroids.
      Special computer programs were developed that starting from a lead compound
      generate complete libraries of possible soft analogs and then help ranking these
      candidates based on molecular size/shape, electronic properties, predicted
      solubility/partition properties, and atomic charge distributions. Recent
      developments in the field are presented in a supplement to this issue.

PMID- 9266588
TI  - Search for novel leads for histamine H3-receptor antagonists: oxygen-containing
      derivatives.
AB  - This study was performed in order to develop new leads for antagonists of the
      histamine H3-receptor subtype. omega-(1 H-Imidazol-4-yl)alkyl derivatives with
      ester, ketone or alcohol functionality in the side chain were synthesized and
      tested concerning their H3-receptor antagonist activity on synaptosomes of rat
      cerebral cortex. The novel compounds, which possess no nitrogen-containing polar
      group in the side chain of the imidazole moiety, presented moderate to high
      antagonist potency in vitro. In this series 3-(1 H-imidazol-4-yl)propyl-3
      cyclopentylpropanoate (4) was the most potent compound in vitro with -log Ki =
      8.5. Unfortunately, no central antagonist H3-receptor activity was detectable for
      ester derivatives in the in vitro H3-receptor assay based upon measurement of
      brain N tau-methylhistamine levels after p.o. administration to mice. Some of
      these novel antagonists are useful tools for investigations on ligand-receptor
      interaction because of their distinct receptor activities. On the other hand, the
      ketone derivative 1-(1 H-imidazol-4-yl)-7-phenyl-4-heptanone (9) in vitro
      presented an ED50-value of 3.5 +/- 1.5 mg/kg p.o. thus proving to be a new lead
      for further drug investigations. The most potent compounds in vitro and in vivo
      also showed high H3-receptor selectivity when tested at other histamine receptor
      subtypes.

PMID- 9266589
TI  - Non-compartmental analysis of pharmacokinetic data after multiple intravenous and
      oral administration.
AB  - Non-compartmental analysis is routinely used to determine the pharmacokinetic
      parameters such as area under the curve (AUC), area under the first moment curve
      (AUMC), clearance (CL), mean residence time (MRT), terminal half life (t1/2) and
      volume of distribution (Vd). These parameters are important to define the fate of
      a drug after administration by a particular route. It is well known that the AUC
      after a single dose is equivalent to that after multiple dose at steady state
      during one dosing interval. However, this relationship is not true for AUMC.
      Hence, it is not possible to calculate MRT as the ratio of AUMC and AUC from
      multiple dose data. It was the purpose of this presentation to evaluate the
      calculation of MRT for single and multiple dosing after intravenous and oral
      administration and compare two different approaches to determine MRT from
      multiple dose data. The results show that after multiple dosing MRT is most
      reliably determined by continuous sampling after the end of the last dosing
      interval until no more drug can be detected.

PMID- 9266590
TI  - Design of a method for in vitro studies of polymer adhesion.
AB  - In this paper we describe a modified intestinal perfusion technique for
      investigation of bioadhesion phenomena. This technique is an in vitro method with
      well standardized experimental conditions which measures the intestinal
      intraluminal pressure and its oscillation. This also allows the vitality of the
      intestinal segment used in the experimental to be checked. Our results suggest
      that the longest adhesion occurred with polyacrylic acid, in comparison with
      carboxymethylcellulose sodium and the shortest with hydroxypropylcellulose.

PMID- 9266591
TI  - Genotoxic properties of the newly synthesized antineoplastic agents amidox, didox
      and trimidox.
AB  - Toxic and genotoxic effects of three polyhydroxy-substituted benzohydroxamates
      (amidox, didox and trimidox), having antineoplastic activities by the mechanism
      of the ribonucleotid reductase activity inhibition, were evaluated by reverse
      mutation assay on Salmonella typhimurium strains TA97, TA98, TA100, TA102. While
      amidox did not exhert any toxic effect, didox and trimidox were toxic. The
      toxicity of the test chemicals was dependent on the structure of their molecule
      and the repair capacity of the test strains. Trimidox exhibited the highest
      toxicity, and it was proved as a direct-acting frameshift mutagen. Its mutagenic
      effect was increased after a metabolic activation. Amidox and didox can be
      classified as frameshift promutagens.

PMID- 9266592
TI  - In vitro postantibiotic effect of imipenem and enoxacin alone and in combination
      against Pseudomonas aeruginosa.
AB  - The postantibiotic effects (PAEs), i.e. suppression of growth of three
      Pseudomonas aeruginosa strains (386, 648, 659) after a short treatment (30 min)
      with imipenem and enoxacin alone and in combination were evaluated. Imipenem (2 x
      MIC) induced PAEs for two strains for 0.5 h (386, 648) at concentrations of 4 x
      MIC, PAEs lasted 0.8 h (386), 2 h (648) and 1.5 h (659). The PAE values of
      enoxacin (2 x MIC) were 4.6 h (386), 1.7 h (648), 1.6 h (659) and those of
      enoxacin (4 x MIC) were 6.1 h (386), 3.2 h (648) and 2.1 h (659). PAEs manifested
      by an imipenem/enoxacin combination were longer than the mathematical sum of PAEs
      induced by individual antibiotics. Prolongation of PAEs induced by the imipenem
      (2 x MIC)/enoxacin (2 x MIC) combination was 25.5% and 27.3% (strains 386 and
      648) as well as 27.8%, 32.4% and 16.1% (strains 386, 648 and 659) after treatment
      with imipenem (4 x MIC)/enoxacin (2 x MIC).

PMID- 9266593
TI  - The discovery of alkaloids.
AB  - This paper presents the history of the discovery of the first alkaloids.
      Isolation of alkaloids is connected with the study of the active principles of
      medicines of plant origin, for example opium and cinchona bark. Serturner
      described morphine as a plant alkali and claimed that it was capable of
      neutralizing free acids yielding salts. The recognition of alkaloids as a new
      class of compounds was an important step at that time because of the dogmatic
      denial of the possible existence of plant bases. Isolation of alkaloids is a
      significant event from the point of view of chemistry, physiology and medicine.
      The discovery caused essential conceptual changes in chemistry. Priority claims
      with reference to the discovery of the alkaloids are also reviewed.

PMID- 9266594
TI  - Synthesis of some 2,6-bis(alkylthio)-4-pyridine carboxamides and carboxthioamides
      and their antimycobacterial and antialgal activity.

PMID- 9266595
TI  - Biological active acridine derivatives. Part 3: acridinylamino acids and their
      esters; synthesis and cytostatic activity.

PMID- 9266596
TI  - Absence of association between angiotensin I-converting enzyme (ACE) DD genotype
      and the frequency of ACE inhibitor therapy.

PMID- 9266597
TI  - Pinobanksin inhibits peroxidation of low density lipoprotein and it has electron
      donor properties reducing alpha-tocopherol radicals.

PMID- 9266598
TI  - Effect of platinum(II) choline complex on murine leukemias L1210 and P388.

PMID- 9266599
TI  - The regulation of tyrosinase gene transcription.
AB  - Tyrosinase is one of the key enzymes essential for melanogenesis. The control of
      its activity rests in part at the level of transcriptional regulation. The 5'
      promoter regions of the human, mouse, chicken, quail, snapping turtle, and frog
      tyrosinase sequences have been isolated and the mechanisms regulating the
      activity of these sequences are beginning to be elucidated. This review provides
      an update on the following aspects of tyrosinase gene regulation: basal promoter
      elements that determine the site of transcription initiation for RNA polymerase
      II; the cis-acting elements and DNA-binding factors that mediate melanocyte
      specific expression of the tyrosinase gene; promoter elements involved in the
      temporal control of tyrosinase gene expression; additional elements that may be
      required to achieve wild-type levels of gene expression; and specific elements
      that may be required for modulation of tyrosinase gene expression in response to
      humoral factors or external stimuli that are known to influence the amounts of
      melanin synthesized by fully differentiated melanocytes. The wild type expression
      of tyrosinase is the result of the interaction of many different factors and it
      is becoming evident that certain elements and factors play more than one role in
      this process.

PMID- 9266601
TI  - The effects of calcium and magnesium ions on the proliferation of normal human
      epidermal melanocytes.

PMID- 9266600
TI  - Effect of maltol on the oxidation of DL-DOPA, dopamine, N-acetyldopamine (NADA),
      and norepinephrine by mushroom tyrosinase.
AB  - Maltol (3-hydroxy-2-methyl-4H-pyran-4-one) appears to inhibit the rate of
      oxidation of DL-DOPA, dopamine, NADA and epinephrine by tyrosinase when assayed
      spectrophotometrically but not when assayed polarographically. Maltol has an
      effect on the spectrum of product(s) formed when each catecholamine was oxidized
      by tyrosinase showing that maltol hastens the disappearance of the quinones,
      possibly by conjugating with them. Indeed, at relatively high concentrations,
      maltol prevented the conversion of DL-DOPA, dopamine, and norepinephrine to their
      corresponding melanins via tyrosinase.

PMID- 9266602
TI  - Regulation of the tyrosinase promoter in transgenic mice: expression of a
      tyrosinase-lacZ fusion gene in embryonic and adult brain.
AB  - The enzyme tyrosinase is indispensable for pigmentation and the gene is expressed
      mainly in pigment cells. Regulatory elements, at -12 to -15 kb (enhancer) and
      within the 270 bp directly upstream of the transcription start site, have been
      described recently and their importance demonstrated in transgenic experiments.
      We were interested in tyrosinase promoter activity during development and used
      beta-galactosidase as reporter gene. Transgenic mice were generated carrying a
      tyrosinase-lacZ fusion gene, containing 6.1 kb of tyrosinase 5' sequences. In
      transgenic embryos, beta-galactosidase activity was detected along the entire
      neural tube, with the most prominent expression in the developing telencephalon,
      and also in the adult brain. Equivalent expression was observed in the developing
      retina. Tyrosinase protein was identified in embryonic and adult brain, but no
      DOPAoxidase or tyrosine hydroxylase activity was detected. From our results we
      conclude that 1) tyrosinase protein is present in embryonic and adult mouse brain
      and 2) the tyrosinase promoter can direct expression of a reporter gene to
      pigment cells and neural tissues.

PMID- 9266603
TI  - Melanin: a two edged sword?
AB  - Melanin is both photosensitizer and photoprotector. Skin cancer rates decrease
      with increasing constitutive pigmentation, yet the pigment has been shown to be
      photoreactive and capable of producing damaging reactive oxygen species. We
      utilized model systems of related cells or similar cell type that vary in
      constitutive and in induced pigment. Induction of eumelanin in Cloudman S91 mouse
      melanoma cells leads to less UV-induced killing and to less mutation induction at
      the ouabain locus (Na+, K(+)-ATPase). Pigmented mouse melanocytes, melan-b
      (brown) and melan-a (black) were slightly less sensitive than melan-c (albino)
      melanocytes to killing after UVC and UVA but were more sensitive to killing after
      UVB and UVB + UVA. Pigment had a small sensitizing effect on pyrimidine dimer DNA
      damage in both the melanoma cells and the melanocytes. The lack of consistency in
      these results suggests that intracellular pigment may disregulate the milieu
      interieur resulting in end effects that are unrelated to the original genomic
      damage.

PMID- 9266604
TI  - Prediction of outcome for patients with cutaneous melanoma.
AB  - Most patients with primary melanoma are cured by local surgery, but a significant
      minority develop fatal metastases. The ability to identify patients with
      progressive disease is central to efficient management: permitting optimal
      deployment of adjunctive therapy and sparing the non-progressing majority the
      morbidity of aggressive therapy. Accurate prediction on an individual patient
      basis is the ideal, but the best current prognosticators permit only assignment
      to risk categories. Formulaic combinations of well tried correlates of outcome
      (gender, ulceration, depth, thickness, and mitotic rate increase accuracy of
      prediction, but not to personalised level. The use of large data bases against
      which the attributes of individual patients may be compared is useful and
      amalgamation of data bases will increase the availability of this approach. The
      development of markers of proliferation fraction (PCNA and MIB-1) and of the
      metastatic phenotype (PNA-receptor status) will further refine the process.
      Staging of disease is critical. Accuracy of staging is improved by mapping the
      (sentinel) lymph nodes likely to contain early tumor by lymphoscintigraphy and
      dye/radiomarker localisation. The application of exquisitely sensitive
      immunohistochemical and molecular biological techniques to biopsies from tissues
      likely to be the site of metastases permit assessment of clinical stage with a
      previously impossible degree of accuracy (ultrastaging).

PMID- 9266605
TI  - Transgenic medaka fish bearing the mouse tyrosinase gene: expression and
      transmission of the transgene following electroporation of the orange-colored
      variant.
AB  - Transgenic fish bearing the mouse tyrosinase gene (mg-Tyrs-J) were produced by
      transfection into fertilized eggs of the homozygous normal orange-colored variant
      of medaka fish, Oryzias latipes, by means of electroporation. Of 589 eggs
      transfected, 38 fish (6%) exhibited brownish wild-type skin pigmentation, which
      was discernible from control siblings. Light microscopy of the skin from the
      founders thus generated disclosed that 1) melanization occurred and was
      restricted to melanophores formed presumably from pre-existing amelanotic
      melanophores, 2) there was a wide variation in the degree of melanization
      observed among melanophores, and 3) no melanin deposition was recognized in
      xanthophores or leucophores. Immunofluorescence using an antibody raised against
      mouse tyrosinase disclosed that melanophores at varying stages of maturation were
      reactive. Thus, it was shown that the transgene in medaka fish expressed its
      action in a cell type-specific manner. Crossing of transgenic founders with
      homozygous orange-colored variant fish yielded two groups of offspring expressing
      either the wild-type or the orange-colored skin pigmentation at an approximate
      ratio of 1:1. Crossing between founders exhibiting wild-type pigmentation yielded
      only offspring with melanized skin. Skin melanophores in these offspring formed
      vertical stripes, which are rare in this species. The hereditary basis of
      melanized skin was demonstrated in matings of F1 progenies, which resulted in
      similar degrees of melanization over whole skin melanophores. The sum of these
      findings implied that the transgene is expressed as a dominant character gene and
      is transmitted through germ cell lines according to the Mendelian law. PCR
      analysis combined with nested PCR technique strongly suggested that the transgene
      was integrated into the medaka genome, even though the copy number deduced from
      gel banding was largely diminished, possibly as a result of fragmentation or
      instability within the medaka genome.

PMID- 9266606
TI  - Clinical, pathological, and etiologic aspects of acquired dermal melanocytosis.
AB  - To study the pathogenesis of acquired dermal melanocytosis (ADM), we reviewed the
      clinical, immunohistochemical, and ultrastructural features of 34 cases (female,
      33, and male, 1) of ADM. The patients' ages at onset ranged from 8 to 51 years
      and averaged 26.8 +/- 12.7 years. There was a positive family history. Gray-brown
      macules were mostly recognized on the face. Not only active dermal melanocytes
      but also non-pigmented c-KIT- and TRP-2-positive immature melanocytes were
      detected in the dermis. Taken together those clinical and histological findings,
      activation of pre-existing immature melanocytes by sunlight, estrogen, and/or
      progesterone, and some other factors, may be the most likely mode of the
      development of ADM. Moreover, using cultured murine neural crest cells as a model
      of c-KIT-positive immature melanocytes, we confirmed that endothelin-1, which is
      produced and secreted by keratinocytes after UV-irradiation, affects melanocytes
      and accelerated melanogenesis.

PMID- 9266607
TI  - Luminol-enhanced chemiluminescent response of human melanocytes and melanoma
      cells to hydrogen peroxide stress.
AB  - The response of human melanocytes and melanoma cells to hydrogen peroxide stress
      was measured. Cells were exposed to glucose/glucose oxidase or free H2O2 and
      reactive oxygen species measured by luminol-enhanced chemiluminescence. The
      response was distinctly different between the two types and the addition of
      superoxide dismutase to melanoma cells paradoxically enhanced the
      chemiluminescent signal. These findings coupled with other known differences
      between the way these two types of cells handle oxidative stress at a molecular
      level suggests that a therapeutic window may be available for exploitation.

PMID- 9266608
TI  - Behavioral phenotypes of inbred mouse strains: implications and recommendations
      for molecular studies.
AB  - Choosing the best genetic strains of mice for developing a new knockout or
      transgenic mouse requires extensive knowledge of the endogenous traits of inbred
      strains. Background genes from the parental strains may interact with the mutated
      gene, in a manner which could severely compromise the interpretation of the
      mutant phenotype. The present overview summarizes the literature on a wide
      variety of behavioral traits for the 129, C57BL/6, DBA/2, and many other inbred
      strains of mice. Strain distributions are described for open field activity,
      learning and memory tasks, aggression, sexual and parental behaviors, acoustic
      startle and prepulse inhibition, and the behavioral actions of ethanol, nicotine,
      cocaine, opiates, antipsychotics, and anxiolytics. Using the referenced
      information, molecular geneticists can choose optimal parental strains of mice,
      and perhaps develop new embryonic stem cell progenitors, for new knockouts and
      transgenics to investigate gene function, and to serve as animal models in the
      development of novel therapeutics for human genetic diseases.

PMID- 9266609
TI  - Serotonin1B receptor modulation of startle reactivity, habituation, and prepulse
      inhibition in wild-type and serotonin1B knockout mice.
AB  - Two operational measures of central information processing mechanisms are
      habituation and prepulse inhibition (PPI) of the startle response. Both measures
      can be assessed reliably in humans and other animals, and have been shown to be
      deficient in patients with schizophrenia. The three present experiments assessed
      the involvement of the serotonin1B (5-HT1B) receptor in modulating startle
      reactivity, habituation, and PPI by comparing 5-HT1B receptor gene knockout (5
      HT1B knockout) with wild-type 129/Sv mice. In experiment I, female mice received
      saline, 2.0 mg/kg 5-methoxy-3(1,2,3,6)tetrahydropyridin-4-yl-1H-indole (RU24969),
      a 5-HT1A/1B agonist, and 1.0 mg/kg 8-hydroxy-2(di-n-propylamino)tetralin (8-OH
      DPAT), a selective 5-HT1A agonist. Female mice received saline, 10.0 mg/kg
      RU24969, and 5.0 mg/kg 8-OH-DPAT in experiment 2, and male mice received saline,
      10.0 mg/kg RU24969, and 5.0 mg/kg 8-OH-DPAT in experiment 3. All three studies
      used identical within-subjects designs. Two phenotypic differences were observed
      following saline treatment: 5-HT1B knockout mice consistently exhibited a small
      increase in PPI that achieved significance in experiment 1; and 5-HT1B knockout
      male mice exhibited robust decreases in startle reactivity. Habituation was
      disrupted consistently by RU24969 in wild-type but not in 5-HT1B knockout mice,
      while 8-OH-DPAT had no effect on habituation. Consistent with the phenotypic
      difference in PPI, the high dose of RU24969 significantly and consistently
      reduced PPI in wild-type but not in 5-HT1B knockout mice. 8-OH-DPAT increased PPI
      in both wild-type and 5-HT1B knockout mice in every experiment. These findings
      suggest that 5-HT1B receptors modulate startle reactivity, habituation, and PPI
      in mice. Additionally, a potential species difference may exist in the behavioral
      effects of 5-HT1A receptor activation on PPI.

PMID- 9266610
TI  - Absence of central cholinergic deficits in ApoE knockout mice.
AB  - ApolipoproteinE (ApoE) genotype has recently been identified as a major risk
      factor for Alzheimer's disease (AD) but the mechanism(s) by which ApoE isoforms
      influence this disease remain unclear. Recent studies suggest that mice deficient
      in ApoE may exhibit impaired central cholinergic function. Since this
      neurotransmitter system has traditionally been associated with the pathogenesis
      of AD, we have further investigated the impact of ApoE gene deletion on this
      system. Female ApoE knockout (ko) mice, age 12 months, were compared with wild
      type littermate controls using a range of behavioural, biochemical and
      histochemical techniques. Pre-treatment with the cholinomimetic, donepezil
      (E2020; 2.5-5 mg kg-1 IP), produced significant hypothermia and induction of
      tremor in both wild type and ApoE ko mice. The magnitude of change did not
      significantly differ between the groups. Cognitive testing in the Morris water
      maze revealed that both wild type and ApoE ko mice could learn the location of a
      hidden escape platform with similar rates of acquisition and accuracy. Similarly,
      the behaviour of both genotypes proved indistinguishable in a Y-maze spontaneous
      alteration procedure. The protocols used for both cognitive tests were then shown
      to be sensitive to the disruptive effects of scopolamine (but not scopolamine
      methyl bromide). Following behavioural testing, choline acetyltransferase (ChAT)
      activity was measured in the hippocampus, frontal and entorhinal cortex and
      striatum. In each case there was no difference between the genotypes. In
      addition, coronal sections of striatum and anterior hippocampal regions of ApoE
      ko and wild type mice showed similar patterns of acetylcholinesterase (AChE)
      staining, with no qualitative or obvious quantitative difference. Finally,
      analysis of plasma cholesterol levels confirmed ApoE genotype. In conclusion,
      using a combination of behavioural, histochemical and biochemical measurements,
      we have failed to detect any significant differences in central cholinergic
      activity between wild type and ApoE ko mice.

PMID- 9266611
TI  - Behavioral reactivity to aversive stimuli in a transgenic mouse model of impaired
      glucocorticoid (type II) receptor function: effects of diazepam and FG-7142.
AB  - Transgenic mice with impaired type II-glucocorticoid receptor mediated feedback
      inhibition of hypthalamic-pituitary-adrenal activity were assessed in three
      different tests assessing behavioral reactivity to aversive stimuli, the elevated
      plus maze, the Thatcher-Britton novelty-conflict paradigm, and the startle
      paradigm. Transgenic mice more frequently entered and spent more time in the open
      arms of the elevated plus in comparison to B6C/3F1 mice. Transgenic mice took
      significantly longer to begin eating in the Thatcher-Britton novelty conflict
      paradigm, and displayed increased reactivity in the startle paradigm.
      Administration of 1 or 2 mg/kg diazepam reversed the behavioral effects observed
      in all three tests. Administration of the benzodiazepine receptor inverse agonist
      N-methyl-beta-carboline-3 carboxamide (FG-7142, 10 mg/kg) reduced the ratio of
      open to total arm entries and the time spent in the open arms of the plus maze in
      transgenic, but not B6C/3F1, mice. This dose of FG-7142 did not influence
      performance of either strain in the Thatcher-Britton or startle paradigms. These
      results are discussed in terms of the hypothesis that the transgenic mice are
      more sensitive to the aversive properties of novel stimuli, and that they may
      have difficulty discriminating between signals of relative safety and danger.

PMID- 9266612
TI  - Brain dopamine receptor plasticity: testing a diathesis-stress hypothesis in an
      animal model.
AB  - A wealth of clinical data supports a major role of genetic liability as well as
      of altered brain dopamine (DA) functioning in different types of behavioural
      disturbances. Genetic influence on behaviour involves multiple genes, rather than
      one or two major genes, as well as non-genetic sources of variance. Thus, in
      recent years, increasing attention has been devoted to the involvement of
      stressful experiences (life events) in the development and expression of
      psychopathology. Moreover, a diathesis-stress hypothesis has been proposed, which
      suggests that the environmental factors (stress) are not specific for a given
      pathology, whereas genetic factors (diathesis) are. Results obtained in an animal
      model offer support to this hypothesis. Indeed, mice of the C57BL/6 and DBA/2
      inbred strains are equally susceptible to stress but develop different
      behavioural disturbances related to different alterations of brain DA receptors.
      Moreover, quantitative trait loci (QTL) associations in the C57 (B) x DBA (D)
      recombinant inbred (RI) strains indicate a number of provisional QTLs influencing
      the behavioural effect of stress. Finally, the results of this analysis suggest
      the involvement of regulatory factors related to stress response and neural or
      synaptic plasticity in the control of brain DA receptor plasticity.

PMID- 9266613
TI  - Differential cocaine sensitivity between two closely related substrains of C57BL
      mice.
AB  - While there is evidence that individual differences in response to cocaine are
      mediated, in part, by genetic factors, no single gene has been identified that
      can account for differential responsivity to cocaine. Recent studies in our
      laboratory may have moved us closer to identification of the gene(s) underlying
      cocaine sensitivity. We have identified several cocaine-related phenotypes on
      which two substrains of C57BL mice (6J and ByJ) differ. The genealogy of these
      two substrains leads to the expectation that they should be genetically very
      similar, differing at only a few loci. The large differences between the two
      substrains in cocaine sensitivity may be influenced by allelic differences at a
      major gene mediating the actions of cocaine. Naive ByJ mice are more resistant to
      cocaine-induced seizures than are 6J mice. Furthermore, among 6J mice repeated
      exposure to cocaine results in a decreased susceptibility to cocaine-induced
      seizure, while among ByJ mice, the same treatment gives rise to an increased
      susceptibility to seizures. In contrast to their lower sensitivity to cocaine
      induced seizures, ByJ mice show a greater sensitivity to cocaine's locomotor
      stimulant effects. Furthermore, the repeated pairing of cocaine and the test
      environment results in the development of conditioned locomotion during
      subsequent exposure to that environment among 6J, but not ByJ, mice. Similarly, a
      greater degree of conditioned sensitization to the locomotor stimulant effects of
      cocaine develops in 6J mice.

PMID- 9266614
TI  - Inbred strain differences in prepulse inhibition of the mouse startle response.
AB  - Prepulse inhibition is the phenomenon in which a weak prepulse stimulus
      suppresses the response to a startling stimulus. Patients with schizophrenia have
      impaired prepulse inhibition which is thought to reflect dysfunctional
      sensorimotor gating mechanisms. To investigate the potential genetic basis for
      differences in sensorimotor gating, the responses of 13 inbred strains of mice
      were evaluated using the prepulse inhibition paradigm. Ten male mice from A/J,
      AKR/J, BALB/cByJ, BUB/BnJ, C3H/HeJ, C57BL/6J, C57BL/10J, DBA/2J, FVB/NJ, ST/bJ,
      129/J, 129/SvJ, 129/SvEvTac inbred strains were tested for acoustic prepulse
      inhibition of acoustic and tactile startle responses. There was a wide range of
      responses among the inbred strains of mice. Exact strain distributions were
      determined for each combination of prepulse sound level and startle stimulus. In
      general, mice from the 129/SvEvTac, AKR/J, 129/J, and 129/SvJ strains displayed
      high levels of prepulse inhibition of both the acoustic and tactile startle
      responses. C57BL/6J, C57BL/10J and BUB/BnJ mice showed low levels of prepulse
      inhibition. There was also a wide range in the amplitude of the acoustic and
      tactile startle responses. C57BL/10J and FVB/NJ mice displayed the greatest
      startle responses and DBA/2J, 129/J and 129/SvJ had the poorest startle
      responses. There was no correlation between the level of prepulse inhibition and
      the amplitude of the startle response. These findings indicate that inbred
      strains of mice may be a useful tool to study the genetic basis of sensorimotor
      gating.

PMID- 9266615
TI  - Differences in vulnerability and susceptibility to dexamphetamine in Nijmegen
      high and low responders to novelty: a dose-effect analysis of spatio-temporal
      programming of behaviour.
AB  - Susceptibility to behavioural effects of dexamphetamine (0.5-2.0 mg/kg, SC) was
      analyzed in Nijmegen high responders to novelty (HR) and Nijmegen low responders
      to novelty (LR), using an automated ethological analysis. The main results were
      that, first, dexamphetamine was more toxic in HR than LR: 5.0 mg/kg
      dexamphetamine was lethal in 75% HR, respectively, 25% LR. Second, dexamphetamine
      had effects in HR at doses far lower than in LR: a dose of 0.5 or 1.0 mg/kg
      dexamphetamine was already sufficient to produce ceiling effects in HR, whereas a
      minimum dose of 2.0 mg/kg dexamphetamine was required to reach effects of a
      similar magnitude in LR. Third, the behavioural responses to 2.0 mg/kg
      dexamphetamine did not differ between HR and LR. These data show that HR are both
      more vulnerable and more susceptible to the toxic and behavioural effects of
      intermediate doses of dexamphetamine than LR. It is concluded that knowledge
      acquired previously about the neurochemical differences between Nijmegen HR (APO
      SUS) and Nijmegen LR (APO-UNSUS) rats can be used to analyze further the
      mechanisms of action underlying individual-specific differences in drug abuse in
      animals and man.

PMID- 9266616
TI  - Different behavioral effects of daily or intermittent dexamphetamine
      administration in Nijmegen high and low responders.
AB  - Outbred strains of Wistar rats contain both high responders to novelty (HR) and
      low responders to novelty (LR). Male HR and LR selected from the Nijmegen outbred
      strain of Wistar rats differ in their sensitivity to acute administration of
      dexamphetamine (AMPH). Sub-chronic administration of AMPH sensitizes rats to this
      agent, and this sensitization (SENS) increases when an intermittent, instead of
      continuous, regimen is used. Thus, the question arose whether HR and LR also
      differ in the development of sensitization to AMPH. AMPH (0.5 mg/kg SC) was given
      five times either each consecutive day (daily: DAY) or each alternate day
      (intermittent: INT). Drug-induced changes in the spatio-temporal patterning of
      open field behavior were assessed for a period of 45 min. Three sets of data were
      found: i) in the AMPH-DAY conditions: total number of excursions with 0 stops
      increased in time: this SENS was far greater in HR than in LR: ii) the effects
      under AMPH-DAY conditions were far greater that those under AMPH-INT conditions,
      especially in HR: iii) under AMPH-INT conditions a new phenomenon was observed:
      following a period in which SENS occurred, a period marked by desensitization
      appeared which, in turn, was followed by a period with SENS being greater than
      the SENS seen during the first time; this effect was far more pronounced in HR
      than in LR. It is concluded that AMPH-INT induces time-dependent changes marked
      by consecutive periods of SENS and desensitization. This has far-reaching
      consequences for hypotheses about processes giving rise to the development of (1)
      SENS to psychostimulants and, consequently, (2) certain aspects of addiction to
      these drugs.

PMID- 9266617
TI  - Naloxone blocks anxiolytic-like effects of benzodiazepines in Swiss but not in
      Balb/c mice.
AB  - The ability of naloxone to block the effects of the benzodiazepines
      chlordiazepoxide and diazepam was evaluated in Swiss and Balb/c mice subjected to
      the light/dark choice test of anxiety or to a choice paradigm for measuring
      spontaneous exploratory behaviour. In Swiss mice, naloxone (5 or 10 mg/kg)
      completely or partially suppressed the anxiolytic-like effects of
      chlordiazepoxide (5 mg/kg) and diazepam (1 mg/kg) in the light/dark test.
      Naloxone alone was ineffective. None of these compounds affected locomotion in
      the free exploratory test. In Balb/c mice, naloxone did not reduce the anxiolytic
      like action of benzodiazepines in the light/dark test. Moreover, naloxone did not
      antagonize the decrease in neophobia observed after anxiolytic treatment in
      Balb/c mice in the free exploratory paradigm. In this strain, benzodiazepines
      produced an increase of locomotor activity, whereas naloxone decreased it. The
      stimulant effects of benzodiazepines on locomotor activity were abolished by
      naloxone. As naloxone (2 mg/kg) reversed the morphine-induced hyperthermia both
      in Swiss and in Balb/c mice, differences in possible pharmacokinetic factors
      between the two strains can be ruled out as an explanation for the failure of
      naloxone to antagonize anxiolytic-like effects in Balb/c mice. Therefore, the
      ability of naloxone to reverse anxiolytic effects does not hold for all strains
      of mice.

PMID- 9266618
TI  - The effects of cocaine on operant responding for food in several strains of mice.
AB  - The availability of numerous genetically homogenous mouse strains permits the
      analysis of genetic influences on behavior and also behavioral sensitivity
      (responsivity) to drugs of abuse. The current study was conducted to characterize
      discriminated operant responding for food in four inbred strains (Balb/cByJ,
      DBA/2J, C57BL/6J, SJL/J), an F1 Hybrid (C57BL/6xSJL), and one outbred strain
      (CD1) of mouse. The effect of cocaine on this operant behavior was also examined.
      Initially, all animals were trained to nosepoke for food on a continuous
      reinforcement schedule. The minimum response requirement for reinforcement was
      increased every 5 days until the animals were responding on an FR-15 schedule of
      reinforcement. All strains increased operant responding as the schedule of
      reinforcement was raised. However, significant differences in response rate and
      discrimination learning were observed among the various strains of mice. Cocaine
      administration reduced operant responding for food in Balb/cByJ, C57BL/6J,
      C57BL/6xSJL/J and CD1 mice at a dose of 15.0 mg/kg, whereas higher doses were
      required in DBA/2J mice (30.0 mg/kg) and SJL/J mice (56.0 mg/kg). These results
      suggest that operant performance and the effect of cocaine on this behavior is
      differentially influenced by genetic make-up.

PMID- 9266619
TI  - Rapid spinal trabecular bone loss in female patients with ileitis terminalis
      Crohn and additional sacroiliac joint inflammation.
AB  - Patients with Crohn's disease are well known to have local and generalized
      osteopenia of varying degrees. The aim of this study was to investigate whether
      the additional involvement of the sacroiliac joint as an extraintestinal
      manifestation has an influence on bone turnover in female patients with Crohn's
      disease. Osteocalcin and other parameters of bone metabolism were measured in 79
      female patients with Crohn's disease. Bone mineral density (BMD) was measured
      using dual energy X-ray absorptiometry (DEXA). Z scores were obtained by
      comparison with age- and sex-matched normal values. As regards the sacroiliac
      involvement (n = 26; group 1), we found a significantly lower BMD in the lumbar
      spine (L4) and in Ward's triangle of the femoral neck compared to controls (P <
      0.05) and those patients (n = 53; group 2) with pure ileitis terminalis Crohn.
      Furthermore, the duration of the disease process in patients with Crohn's disease
      and extraintestinal involvement was markedly shorter than that of patients in
      group 2 (P < 0.05). In conclusion, osteoporosis in female patients with
      sacroiliac involvement manifested itself in a more severe way.

PMID- 9266620
TI  - Toxicity profile of dual methotrexate combinations with gold, hydroxychloroquine,
      sulphasalazine and minocycline in rheumatoid arthritis patients.
AB  - The purpose of the present study was to evaluate the toxicity and tolerability of
      methotrexate (MTX)/gold (G; group 1) combination therapy as compared to other MTX
      combinations [MTX with hydroxychloroquine (HCQ; group 2), MTX with sulphasalazine
      (SASP; group 3) and MTX with minocycline (MNC; group 4)]. The hospital records of
      127 consecutive rheumatoid arthritis (RA) patients who were treated with these
      combinations during a period of 24 months were retrospectively reviewed. The
      toxicity and tolerability of the MTX/G combination was compared to the other dual
      MTX combinations and also to MTX alone using data previously reported by us on
      126 RA patients treated with single MTX therapy. The mean exposure time to
      treatment was 16 months in group 1 and 13 months in the other dual MTX
      combinations. During the period of follow-up, the combination was stopped in 22
      out of 42 patients in group 1 (52%) in comparison with 54 patients out of 86
      patients (63%) in the other dual regimen groups. The discontinuation rate was
      highest in group 4 (due to side effects and lack of compliance) and this was
      statistically significant in comparison with group 1. The proportion of adverse
      events was lowest in group 1 (14%) and highest in groups 3 and 4 (25%). Side
      effects were reversible and comparable with those of MTX alone (23%). No fatal or
      life-threatening side effects were recorded during any of these MTX combination
      therapies. We concluded that the combinations of MTX with G, HCQ, SASP and MNC in
      RA were relatively well tolerated. No increase in toxicity compared with MTX
      alone was observed. The lowest rate of side effects was noted in group 1, while
      group 4 presented the highest discontinuation rate.

PMID- 9266621
TI  - The effect of intravenous cyclophosphamide pulse on peripheral blood lymphocytes
      in lupus erythematosus patients.
AB  - In the present study we investigated the long-term effect of intravenous pulse
      cyclophosphamide (CY) on lymphocyte surface antigens in systemic lupus
      erythematosus (SLE) patients. Blood samples derived from 17 lupus erythematosus
      patients were analysed using two- and three-colour flow cytometry. During the CY
      therapy, the total number of T lymphocytes (CD3+) was reduced by 31.4%, B
      lymphocytes (CD19+) by 67.4% and NK cells (CD16+) by 27.4%. Six months after the
      end of the CY regimen, these values recovered to entry levels. At the onset of
      the study we observed increased percentages of CD3+ CD25+, CD3+ CD4- CD8-, CD4+
      CD29+, CD19+ and CD19+ CD5+ cells. The CY treatment regimen decreased the CD3+
      CD25+, CD3+ CD4- CD8-, CD19+ and CD19+ CD5+ cells, but increased the CD3+ CD8+
      subpopulation. Taken together, a deficiency of CD8+ T cells associated with CD4+
      CD29+ predominance may imply an immune regulatory imbalance leading to abnormal
      CD4+ cell activation and in consequence to autoimmunity. Depletion of CD19+ cells
      combined with an enlargement of CD8 cells as a result of CY therapy may reduce
      the enhanced immune response in SLE patients.

PMID- 9266622
TI  - Esophageal manometry in systemic sclerosis: screening procedure or confined to
      symptomatic patients?
AB  - The predictive value of esophagus-related symptoms for the diagnosis of
      esophageal dysmotility induced by systemic sclerosis (SSc) was prospectively
      evaluated in 50 consecutive patients with SSc. Patients were classified as
      symptomatic when either dysphagia or repeated episodes of heartburn were present.
      All patients underwent esophageal manometry; SSc-induced esophageal dysfunction
      was diagnosed when there was aperistalsis or marked hypocontractility of the
      distal two-thirds of the esophageal body. Twenty-nine patients (58%) had a
      history of esophagus-related symptoms, while 21 patients (42%) were asymptomatic.
      Compared to esophageal manometry, esophagus-related symptoms had a sensitivity of
      64%, a specificity of 52%, a negative predictive value of 50% and a positive
      predictive value of 62% for the diagnosis of SSc-induced esophageal dysfunction.
      In conclusion, the association of esophagus-related symptoms and esophageal
      motility pattern is poor. As clinical management strategies depend on proof of
      esophageal dysfunction, screening examinations are mandatory in all patients with
      SSc.

PMID- 9266624
TI  - Seizures and hepatotoxicity following sulphasalazine administration.
AB  - Sulphasalazine (SSZ) is a widely used second-line agent for several rheumatic
      diseases. Most of its side effects are relatively minor and dose dependent. We
      report a patient with juvenile onset chronic arthritis who developed
      hepatotoxicity and seizures on the third week of SSZ when the daily dose was
      increased to 2 g. Clinical and laboratory findings of liver and central nervous
      system toxicity gradually returned to normal in the month following SSZ
      withdrawal.

PMID- 9266623
TI  - Availability of iron and degree of inflammation modifies the response to
      recombinant human erythropoietin when treating anemia of chronic disease in
      patients with rheumatoid arthritis.
AB  - Forty-six patients with rheumatoid arthritis (RA) and documented anemia of
      chronic disease (Hb < 100/110 g/l) were randomized to receive either human
      recombinant erythropoietin (r-HuEPO, n = 36, 300 U/kg body weight) or placebo (n
      = 10) for 12 weeks in a multicenter study. An adequate response was defined as
      elevation of Hb > or = 120 g/l. Relevant clinical and laboratory assessments were
      made to evaluate efficacy and secure safety. A significant elevation in Hb from
      week 10 onwards was noted in twenty-six patients (five drop-outs) out of nine
      patients receiving placebo (one drop-out) (12 +/- 1.2 g/l vs 4 +/- 0.5 g/l; Hb
      elevation from 95 g/l to 107 g/l vs 93 g/l to 97 g/l, P < 0.05). Only 14.6%,
      however, were considered responders according to preset criteria. In the
      responders a lower initial CRP, a significant reduction in ESR but not in CRP was
      seen compared to the remaining r-HuEPO group. A significant elevation of energy
      level was noted in the r-HuEPO group; otherwise, no differences in clinical
      variables were seen. No serious adverse effects were noted. When analyzing
      patients receiving oral iron in combination with r-HuEPO and adding five
      additional, openly selected patients receiving both adequate iron supplementation
      and r-HuEPO, there was a significant weekly elevation of Hb from week 8 onwards
      in favor of combination therapy over the ones only receiving r-HuEPO (18 +/- 1.1
      g/l vs 7 +/- 1.1 g/l, P < 0.05). The initial six responders had now reached ten
      of whom seven belonged to the combination therapy group. Response to r-HuEPO in
      RA patients appears to be dependent on availability of iron and on the degree of
      inflammation. If r-HuEPO treatment is considered, iron deficiency should always
      be corrected and strenuous efforts should have been made to control the disease
      itself.

PMID- 9266625
TI  - Coexisting hyperparathyroidism, renal osteodystrophy and psoriatic arthritis.
AB  - We report the case of a 60-year-old woman with hyperparathyroidism, renal
      osteodystrophy and psoriatic arthritis. The coexistence of findings of
      hyperparathyroidism and renal osteodystrophy has been described and there are
      also reports of patients suffering from renal arthropathy mimicking
      hyperparathyroidism. To our knowledge, there is no description to date of a case
      displaying findings of the co-occurrence of these conditions in a patient. We
      would like to emphasize that attention should be paid to the possible diagnosis
      of a coexisting inflammatory rheumatic disease when rheumatological symptoms of
      recent onset occur in patients with long-standing renal osteodystrophy and/or
      symptoms mimicking hyperparathyroidism occur in these patients.

PMID- 9266626
TI  - [The relationship between workers' attitudes towards health, lifestyle and mental
      health].
AB  - In order to investigate the relationship between health practices, various
      psychosocial factors, and mental health, a survey was conducted by means of a
      self-rating questionnaire on 424 industrial workers. The questionnaire included
      items concerning Goldberg's 12 selected items from the Japanese version of the
      General Health Questionnaire, the Type A scale used in the Framingham study,
      Breslow's 7 health practices, and other original psychosocial, health practicing
      items. A total of 391 or 92.2% responded to the questionnaire. Among them, 354
      (266 males and 88 females) complete responders to the GHQ were analysed for the
      present study. As a result, several factors such as decrease in age, perceived
      present illness, worsening of perceived health status, increase in anxiety
      concerning health, exacerbation of alcohol and smoking related behaviour,
      decrease in physical exercise, reduction of Breslow's 7 health practices,
      perceived stress and difficulty in dealing with stress, increase in stress
      content, negative and malfunctional coping strategies, and decrease in relaxation
      were, according to the GHQ scores, related to negative mental health.
      Furthermore, Type A scores were significantly correlated to GHQ scores, the
      number of stress factors, and Breslow's 7 health practices in males, but they
      were weak or had no correlation in females. It is considered that favorable
      health practices and attitudes towards health might help to maintain positive
      mental health, but further analysis is needed to determine their causal
      relationships because of the cross-sectional design of the present study.

PMID- 9266627
TI  - [Study of workload and cervicobrachial disorder among sign language
      interpreters].
AB  - We conducted a nationwide questionnaire study on the workload and health
      conditions of professional sign language interpreters to investigate the
      relationship between occupational cervicobrachial disorders (OCD) and the sign
      language workload. The number of valid respondents was 542 (92.3%), 85.8% of them
      females. They were employed by the national or local governments or organizations
      for the disabled. The complaint rates of subjective symptoms involving the neck,
      shoulders, arms, fingers, eyes and ears, being equal or higher than the rates
      reported for cashiers, telephone operators and nursery school teachers when OCD
      occurred frequently. As the workload of sign language increased, the number of
      complaints of symptoms in the cervicobrachial region, which also includes
      fingers, increased as well. Occupational safety and health management for
      preventing OCD should be carried out immediately for sign language interpreters.

PMID- 9266628
TI  - The quasispecies of hepatitis C virus and the host immune response.

PMID- 9266629
TI  - Histopathology and detection of hepatitis C virus in liver.

PMID- 9266630
TI  - Immune responses throughout hepatitis C virus (HCV) infection: HCV from the
      immune system point of view.

PMID- 9266631
TI  - Immunopathology of hepatitis C.
AB  - Hepatitis C virus (HCV) infection becomes persistent in the majority of instances
      in the face of a humoral and cellular immune response, and persistent HCV
      infection is associated with chronic hepatitis. In particular, cytotoxic T
      lymphocytes (CTL), crucial in the eradication of virus-infected cells, have been
      observed in the liver and the peripheral blood of chronically infected patients,
      suggesting that CTL cannot completely eliminate the virus, and may contribute to
      chronic liver injury. In this review, the potential host and the viral factors
      involved in the pathogenesis of chronic HCV infection will be discussed with
      emphasis on the HLA-A2 restricted peripheral blood CTL response and its
      relationship to liver disease and viral load.

PMID- 9266632
TI  - Characteristics of the intrahepatic cytotoxic T lymphocyte response in chronic
      hepatitis C virus infection.
AB  - Based on our CTL studies of over 44 persons with chronic HCV infection, we are
      able to arrive at a number of conclusions. Clearly this cellular immune response
      is heterogeneous among infected persons. We have not identified any specific HCV
      protein which appears to be immunodominant for CTL responses, but rather we have
      detected diverse responses to both structural and non-structural proteins. Using
      an identical stimulation strategy for all persons studied, we have been able to
      detect responses in only approximately one third of persons with chronic
      infection. Among these persons, the responses among liver-infiltrating
      lymphocytes are greater than those detected in fresh peripheral blood, suggesting
      that the CTL are homing to the site of maximal viral burden in these persons.
      Some viral proteins contain overlapping epitopes presented by more than one HLA
      class I molecule, and we have also found cases where peptides in the same HLA
      superfamily, such as the HLA A3 superfamily which contains A11, for which the
      same peptide can be presented by both alleles (manuscript in preparation).
      Although sequence variation between the infecting strain and the vaccinia
      constructs used to test for responses may lead to non-recognition of some
      variants, even the highly conserved core protein appears to be an inconsistent
      and actually infrequent target for detectable CTL responses. The magnitude of the
      CTL response appears to vary greatly, from being undetectable to being so
      vigorous that it an be detected in stimulated peripheral blood. The breadth of
      the response also varies widely, ranging from the detection of a response to a
      single epitope in some persons, to the simultaneous recognition of up to five
      different epitopes in others. Even in persons of the same HLA type, we have not
      seen consistent targeting of the same epitopes except in rare cases. Despite the
      detection of over 20 epitopes and their restricting class I alleles using CTR
      derived from liver-infiltrating lymphocytes, we have identified only one epitope
      that has been shown to be targeted by more than one person of the same HLA type.
      These findings lead us to speculate that the CTL response may be submaximal in
      the majority of infected persons. The reasons for this are presently obscure, but
      could relate to a number of factors. The epitopes targeted are found within
      variable regions of the virus, such that immune escape from established CTL
      responses has to be considered a real possibility. Sequence variation may also
      lead to antagonism of CTL responses, as has been demonstrated for both HIV and
      HBV infections. Furthermore, sequence variation either within or adjacent to
      regions containing CTL epitopes can lead to altered antigen processing, either
      due to alteration of proteolytic processing of the viral peptides in the
      cytoplasm or to altered transport and altered association with class I molecules.
      A number of issues regarding the CTL response in HCV infection still require
      substantial attention. The apparent inability of CTL to clear this virus needs to
      be addressed, as does the potential role for viral immunomodulatory molecules in
      HCV persistence. Although we and others have shown CTL responses to be present in
      persons with chronic infection, the role of CTL in acute HCV infection needs to
      be determined. The best studied chronic human viral infection is HIV infection,
      in which expanding data indicate that the early events following primary
      infection predict the subsequent course of illness. Viral load in the first 1-2
      years after infection is highly predictive of the subsequent disease course in
      HIV infection, and recent experimental data in humans suggest that early immune
      responses may be predictive of subsequent disease course. Such studies in HCV
      infection have been difficult to achieve, since primary HCV infection is often
      asymptomatic, and transfusion-related cases are now rare. (ABSTRACT TRUNCATED)

PMID- 9266633
TI  - Comparative features of hepatitis C virus infection in humans and chimpanzees.
AB  - Several features of human HCV infection are recapitulated in the chimpanzee
      model. Most importantly, the frequency of persistent infection is high in both
      species, and virus replication occurs despite evidence of cellular and humoral
      immune responses. A key difference is that necroinflammatory lesions in
      chronically infected chimpanzees are almost always mild, whereas in humans the
      disease spectrum is very wide, ranging from mild to severe hepatitis and end
      stage cirrhosis requiring transplantation. Understanding the basis for both the
      similarities and differences in persistent hepatitis C in the two species will
      probably be important for the development of effective prevention and therapy of
      HCV infection.

PMID- 9266634
TI  - Hepatic lymphoid aggregates in chronic hepatitis C and mixed cryoglobulinemia.
AB  - We have examined the clinical (virological and immunological), histological and
      immunohistochemical features of liver lymphoid nodules in hepatitis C virus
      positive (HCV+)/mixed cryoglobulinemia (type II and III) and chronic hepatitis C.
      The clinical features of liver disease were found to be similar in all patients.
      In all these groups, liver lymphoid nodules were observed to a similar extent,
      being more frequent in earlier phases of liver disease and less in more advanced
      stages. These data were confirmed by studies in serial biopsy samples taken from
      individual patients with type II mixed cryoglobulinemia; the loss of lymphoid
      nodules with progression to more advanced histological stages of disease in these
      patients was accompanied by a decrease of the serum levels of cryoglobulins
      (although not statistically significant). By immunohistochemical analysis, the
      liver lymphoid nodules contained predominantly B cells with a CD5+/bcl2+/Ki67-
      phenotype, which were always polyclonal in type III mixed cryoglobulinemia and
      chronic hepatitis C, and monoclonal in type II mixed cryoglobulinemia. These
      immunological features were consistent with an active role of the immune system
      in HCV-associated liver necro-inflammation. Only in type II mixed
      cryoglobulinemia was there a clonal restriction of B cells. The immunological
      profile (autoantibodies) and viral genotypes were examined in some patients, but
      no significant correlation with clinical and immunohistochemical findings was
      found; however, the prevalence of genotype 2a was significantly higher in type II
      mixed cryoglobulinemia than in type III and chronic hepatitis without
      cryoglobulinemia.

PMID- 9266636
TI  - Laparoscopic surgery for cure of colorectal cancer.

PMID- 9266635
TI  - The etiology and pathophysiology of mixed cryoglobulinemia secondary to hepatitis
      C virus infection.
AB  - The strong association of HCV infection with MC-II and the selective
      concentration of the virus with the WA mRF in the cryoglobulins are compelling
      suggestions that the virus is directly involved in production of the mRF and the
      pathophysiology of MC-II. There is, however, only limited data on HCV involvement
      in both processes. In cutaneous vasculitis, which is the most prevalent clinical
      feature of the disease, there is evidence that complexes of HCV, mRF and IgG are
      formed in situ from components of the cryoglobulins that are present in the blood
      in a dissociated state. It is postulated that local factors, cooling and stasis
      predispose to formation of these lesions in the lower limbs. However, since
      cutaneous vasculitis does not correlate with cryoglobulin levels and may not be
      induced by cold challenge, other factors may be involved. In particular, the
      conditions which activate the vascular endothelial cells, leading to the
      leukocytoclastic vasculitis, require delineation. In contrast to cutaneous
      vasculitis, HCV RNA has not been prominently detected in immune complexes in MPGN
      lesions and has not been detected at all in the peripheral neuropathy lesions.
      These preliminary observations suggest that different pathophysiological
      processes are involved in for these lesions than in cutaneous vasculitis. From
      the correlation of remission of disease with decreased cryoglobulinemia and
      viremia in treated patients with MC-II, and from immunohistological data on the
      hepatitic lymphoid follicles in MC-II (see chapter 7), it appears that an antigen
      driven benign proliferation of B cells is responsible for production off mRF and
      cryoglobulinemia. New findings have suggested that one mechanism for developing
      mixed cryoglobulinemia may be that HCV-VLDL complexes that contain apo E2 are
      poorly endocytosed by the LDLR, which may be a major route of entry of the virus
      to the cell; persistence of the complexes in the circulation may then stimulate
      mRF production. This new hypothesis is based only on initial in vitro
      observations and require independent confirmation and validation in vivo. From
      indirect clinical evidence it has also been postulated that mRF in some patients
      may limit the cytopathology in MC-II, resulting in a lower prevalence of
      cirrhosis in these patients. These findings suggested another hypothesis, which
      is that the mRF prevents spread of infection to hepatocytes and other permissive
      and nonpermissive cells by blocking endocytosis of HCV-VLDL complexes by the
      LDLR. Furthermore, data on the composition of cryoglobulins, the molecular
      composition of WA mRF and the characterization of monoclonal B cells in the liver
      of patients with MC-II (see chapter 7) suggest that a specific population of B
      cells may be involved in the host response to HCV infection. These are B cells
      that proliferate with little or no somatic mutations of the immunoglobulin genes,
      are self-replicating, are stimulated by self antigens in a T cell-independent
      manner and bear the CD5 marker. The proliferation of this B cell population may
      be the host's response to the attempt by the virus to circumvent the immune
      response by complexing with host lipoproteins. It is proposed that HCV complexed
      to VLDL is the antigen that directly stimulates the proliferation of these
      primordial type B cells. Testing of these hypotheses may produce insights not
      only into the etiology of mixed cryoglobulinemia but possibly into the mechanisms
      by which HCV circumvents the immune response and established chronic infection.

PMID- 9266637
TI  - Intracorporeal colorectal anastomosis following laparoscopic left colon
      resection.
AB  - BACKGROUND: The aim of this study was to assess the impact of an intracorporeal
      double-stapled colorectal anastomosis upon the outcome of laparoscopic left colon
      resection. METHODS: Fifty-four selected patients underwent elective laparoscopic
      left colon resection for benign disease. Once resection was completed, a 33-mm
      suprapubic port allowed insertion of the anvil of a circular stapler into the
      colon, which was closed by a handsewn purse-string suture using the T-needle
      technique. The circular stapler was passed transanally to perform a double
      stapled anastomosis. Specimens were delivered in a plastic bag via the suprapubic
      port. RESULTS: There were no deaths. Minor intraoperative and postoperative
      complications occurred in 3.7% and 9.2% of the patients, respectively. Median
      operating time was 125 min (range 80-210 min). Complete proximal and distal
      doughnuts were obtained in all patients and anastomoses were all methylene blue
      tight. Median hospital stay was 4 (range 3-7) days. CONCLUSIONS: Fashioning
      double-stapled colorectal anastomoses intracorporeally is feasable and safe.

PMID- 9266638
TI  - Immediately recognizable benefits and drawbacks after laparoscopic colon
      resection for benign disease.
AB  - BACKGROUND: A prospective assessment of the impact of laparoscopic colon
      resection (LCR) was carried out in order to quantify immediately recognizable
      benefits and limitations of this approach. METHODS: Elective LCR was attempted in
      95 selected patients (mean age 64 years, range 39-81 years) presenting with
      benign disease of the colon. A completely intracorporeal approach was adopted.
      Results were compared with a control group of 90 patients who had previously
      undergone open colectomy (OC) by the same surgeons at the same institution.
      RESULTS: There were no perioperative deaths. Intraoperative complications
      included difficult extraction of accidentally detached anvil (n = 1), air leak at
      colonoscopy (n = 2), and conversion to OC (n = 1). Operating time was
      significantly longer after LCR compared with OC (180 +/- 10.3 vs 116 +/- 97, p <
      0.001). Passage of flatus (3.5 +/- 1.2 days vs 4.4 +/- 1.4, p < 0.5) and
      morbidity (4 vs 3, p = 0.48) were not significantly different in the two groups.
      Hospital stay was significantly shorter after LCR (5.2 +/- 1.3 days vs 12.2 +/-
      1.9 days, p < 0.001). Theater and ward costs were, respectively, significantly
      increased ($2,829.6 +/- 340 vs $1,422 +/- 318, p < 0.001) and decreased ($2,600
      +/- 366 vs $6,022 +/- 916, p < 0.001) in LCR patients compared with the OC group.
      There was no significant difference in total hospital costs ($10,929 +/- 369 vs
      $9,944 +/- 1,014). CONCLUSIONS: LCR does not appear to offer any immediately
      recognizable advantages.

PMID- 9266639
TI  - Development of a fogless scope and its analysis using infrared radiation
      pyrometer.
AB  - BACKGROUND: In laparoscopic surgery, fogging of the lens tip instantly degrades
      the quality of image and interrupts the flow of surgical maneuvers. External
      warming devices prevent fogging for a certain length of time, but use of them is
      troublesome at best. These problems prompted us to develop a fogless mechanism
      built into the scope so that the fogless image would be continuous and trouble
      free. We then conducted several experiments that demonstrate the precise effect
      it has on the lens tip. METHODS: The infrared radiation pyrometer was used to
      compare the temperature distribution as well as the temperature change against
      time of each lens tip of the fogless and ordinary laparoscopes. RESULTS: The
      temperature of the lens tip of the ordinary scope did not change, but that of the
      fogless scope rose to 41 degrees C in 184-208 s. CONCLUSIONS: The fogless
      mechanism effectively warms the lens tip to a safe temperature that prevents
      fogging in the intraabdominal environment.

PMID- 9266641
TI  - Cost and benefit of the trained laparoscopic team. A comparative study of a
      designated nursing team vs a nontrained team.
AB  - BACKGROUND: In spite of the emergence of laparoscopic cholecystectomy as the gold
      standard for treatment of symptomatic gallstones, questions still remain
      regarding its overall cost effectiveness, especially at low-volume centers where
      operating room (OR) time and operative complications are higher. We hypothesize
      that the presence of a well-organized, dedicated laparoscopic OR team will
      improve surgical outcomes for this procedure. This study compares the operative
      results of an advanced and a basic laparoscopic surgeon using either a designated
      laparoscopic operating team or a nondesignated team. METHODS: The hospital
      records for 71 elective laparoscopic cholecystectomies with cholangiograms were
      retrospectively reviewed and anesthesia times and conversion rates were analyzed.
      Procedures were performed either at a hospital with a dedicated laparoscopy team
      or a hospital with nondedicated OR personnel. All procedures were done by an
      advanced laparoscopic surgeon or a basic laparoscopic surgeon. RESULTS: Case
      characteristics were evenly matched between sites and surgeons. The mean total
      anesthesia time at the dedicated site was 120.8 min, compared to 152.3 min at the
      nondedicated site with a mean difference of 31.5 min (p = 0.001). A 12%
      conversion rate was documented at the nondedicated site. There were no
      conversions at the site with a dedicated laparoscopy team. No major complications
      were encountered in this series. CONCLUSION: This study demonstrates that having
      a designated laparoscopic trained team provides a time savings to both advanced
      and basic laparoscopic surgeons. Although no major complications were
      encountered, there was a significant conversion rate for the less experienced
      surgeon operating without the support of a trained team. The end result from
      having a dedicated team in endoscopic surgery is decreased operative time, an
      improvement in patient care, and decreased costs to the patient and institution.

PMID- 9266640
TI  - Duration of postlaparoscopic pneumoperitoneum.
AB  - BACKGROUND: Patients who present with abdominal pain after recent laparoscopic
      surgery present a diagnostic dilemma when pneumoperitoneum is present. Previous
      studies do not define the duration of postlaparoscopic pneumoperitoneum. In this
      study, we attempted to define the duration of laparoscopic pneumoperitoneum and
      to identify factors which affect resolution time. METHODS: We followed 57
      patients who underwent laparoscopic cholecystectomy (34), inguinal herniorraphy
      (20), or appendectomy (three). Serial abdominal films were taken until all
      residual gas was resolved. RESULTS: Thirty patients resolved their
      pneumoperitoneum within 24 h; 16 patients resolved between 24 h and 3 days; nine
      patients resolved between 3 and 7 days; two patients resolved between 7 and 9
      days. Mean resolution time for all patients was 2.6 +/- 2.1 days. There was no
      apparent difference in resolution time between the three types of procedures;
      however, the sample size may be insufficient. Duration of the pneumoperitoneum
      did not correlate with gender, age, weight, initial volume of CO2 used, length of
      time for the procedure, or postoperative complications. Sixteen patients had bile
      spillage during cholecystectomy which significantly reduced the duration of
      postoperative pneumoperitoneum (p < 0.008), resulting in a mean resolution time
      of 1.3 +/- 0.9 days. While 14 patients reported postoperative shoulder pain, no
      correlation was found between the presence or duration of shoulder pain and the
      extent or duration of pneumoperitoneum. CONCLUSIONS: We conclude that the
      residual pneumoperitoneum following laparoscopic surgery resolves within 3 days
      in 81% of patients and within 7 days in 96% of patients. The resolution time was
      significantly less in patients sustaining intraoperative bile spillage during
      cholecystectomy. There was no correlation found between postoperative shoulder
      pain and the presence or duration of the pneumoperitoneum.

PMID- 9266642
TI  - Laparoscopy without trocars.
AB  - BACKGROUND: Laparoscopic access devices have consisted of a cannula and sharp
      trocar. A trocarless endoscopic access cannula was designed to improve safety,
      eliminate blind entry, save time, and decrease cost. It consists of a threaded
      hollow cannula with a blunt penetrating distal end. METHODS: After
      pneumoperitoneum is established with the Veress needle, the laparoscope is
      inserted into the cannula, and using the blunt tip at the distal end of the
      thread, the anterior rectus fascia is engaged through a 5-7 mm horizontal fascial
      incision. Rotation advances the blunt cannula tip past the anterior rectus
      fascia, muscle, and posterior rectus fascia and through the peritoneum under
      continuous video control with no axial force. RESULTS: The trocarless rotational
      access cannula (TRAC) was used successfully in 135 consecutive unselected
      patients with no complications. CONCLUSIONS: This access cannula and methods
      offer many advantages while improving safety and cost.

PMID- 9266643
TI  - Percutaneous fetal access and uterine closure for fetoscopic surgery. Lessons
      learned from 16 consecutive procedures in pregnant sheep.
AB  - BACKGROUND: Maternal morbidity and preterm labor from fetal surgery might be
      minimized by a percutaneous technique for fetal access and uterine closure.
      METHODS: In each of 16 ewes, we inserted three trocars percutaneously into the
      amniotic cavity using ultrasound and fetoscopic guidance. In six ewes,
      percutaneous uterine closure after the procedure was attempted. We assessed
      feasibility and acute complications of our technique during surgery and at
      autopsy. RESULTS: We achieved percutaneous fetal access in 14 ewes and closed the
      uterus percutaneously in all six ewes attempted. Fetal injury was related to
      amnioinfusion or fixation of chorioamniotic membranes. Other complications were
      trocar dislodgment and damage to uterine wall and chorioamniotic membranes. The
      latter complication was prevented using balloon-tipped trocars. CONCLUSIONS:
      Percutaneous intraamniotic access and uterine closure for fetoscopic surgery can
      be achieved reliably with little maternal and fetal morbidity in sheep. Minor
      modifications are desired to apply this approach in humans.

PMID- 9266644
TI  - Adhesion formation in laparoscopic inguinal hernia repair.
AB  - BACKGROUND: In laparoscopic inguinal hernia repair controversy exists concerning
      the most appropriate repair method and implant material to use if intraabdominal
      adhesions are to be minimized. METHODS: In 108 pigs, we implanted three different
      types of mesh by both the TAPP (transabdominal preperitoneal) and Onlay
      (prosthesis placed directly upon the peritoneum) methods. Specimens were
      harvested in three time periods and adhesion formation was compared. RESULTS:
      Average adhesions at 3 days were TAPP 18% and Onlay 49% (p < 0.001). At 3 weeks
      average adhesions were TAPP 8% and Onlay 23% (p < 0.04). Three-month figures were
      TAPP 1% and Onlay 13% (p < 0.001). In contrast, there were no differences in
      adhesion formation due to material type in any of the three time periods (all p >
      0.17). CONCLUSIONS: A peritoneal covering over a laparoscopic inguinal implant
      significantly reduced adhesions. Prosthetic material type did not affect adhesion
      formation in this study.

PMID- 9266645
TI  - Laparoscopically assisted gastric surgery using Dexterity Pneumo Sleeve.
AB  - BACKGROUND: Laparoscopic surgery has been successfully applied to several
      gastrointestinal procedures. Although the totally laparoscopic gastrectomy is
      feasible, tactile sensation and manipulation of the organ as well as the lesion
      are decreased when compared to open surgery. The Dexterity Pneumo Sleeve is a new
      device which allows the surgeon to insert a hand into the abdominal cavity while
      preserving the pneumoperitoneum. This device was used for patients who underwent
      laparoscopic gastric surgery. METHODS: The first patient presented with a non
      Hodgkin's lymphoma of the stomach. A laparoscopically assisted distal gastrectomy
      was performed with Roux-en-Y reconstruction. The second patient had a 5-cm
      leiomyoma involving the greater curve of the stomach, and this device was used
      for manipulation of the tumor. The last patient suffered from morbid obesity with
      its associated medical complications and a ventral hernia. The Sleeve was applied
      at the hernia site and a laparoscopically assisted gastric bypass was performed.
      RESULTS: The Pneumo Sleeve was useful in these cases for tactile localization of
      the tumor and for retraction and manipulation of the stomach and surrounding
      upper abdominal organs. CONCLUSIONS: The utilization of this device resulted in a
      more easily performed dissection, resection, and anastomosis and was felt to
      decrease operation time.

PMID- 9266646
TI  - Laparoscopic gastrojejunostomy and endoscopic biliary stent placement for
      palliation of incurable gastric outlet obstruction with cholestasis.
AB  - BACKGROUND: For patients with incurable malignant gastric outlet obstruction and
      cholestasis, laparoscopic gastrojejunostomy combined with endoscopic biliary
      stent placement seems to offer a minimally invasive palliation. METHODS: We
      retrospectively analyzed the data of 16 patients submitted to laparoscopic
      gastrojejunostomy. Laparoscopic gastroenterostomy was performed as an antecolic,
      side-to-side gastrojejunostomy with enteroenterostomy. In 12 patients cholestasis
      was relieved preoperatively by stent placement via endoscopy (n = 6, 37.5%),
      percutaneous access (n = 5, 31%) or bilioenteric anastomosis (n = 1, 6.25%). One
      patient needed a percutaneous Yamakawa prosthesis postoperatively. RESULTS: Mean
      operative time was 126 min. There were no intraoperative complications. In one
      patient conversion to open surgery became necessary because of extensive
      adhesions. The only postoperative complication was bleeding from a trocar site
      requiring reintervention; there was no mortality. Median postoperative hospital
      stay was 7 days. Delayed gastric emptying was observed in 3 (18.7%) patients.
      Median survival was 87 days after the operation. All patients died from their
      primary disease but could maintain oral intake during the remaining survival
      time. CONCLUSIONS: We conclude that laparoscopic gastrojejunostomy and endoscopic
      or percutaneous biliary stenting provide a good functional result while impairing
      the quality of life only to a minimal extent.

PMID- 9266647
TI  - Laparoscopic cholecystectomy and time-course changes in renal function. The
      effect of the retraction method on renal function.
AB  - BACKGROUND: Recently, the retraction method has been used to reduce
      intraabdominal pressure (IAP) during laparoscopic surgery. The purpose of this
      study was to determine the serial changes in renal function during laparoscopic
      cholecystectomy (LC) using the retraction method. METHODS: Urine output,
      effective renal plasma flow (ERPF), and glomerular filtration rate (GFR) were
      measured serially in seven patients who underwent LC with 12 mmHg
      pneumoperitoneum (High-IAP group) and five who underwent LC using the retraction
      method with 4 mmHg pneumoperitoneum (Low-IAP group). RESULTS: Urine output, ERPF,
      and GFR were decreased during pneumoperitoneum in the High-IAP group, whereas no
      significant changes in any of these parameters were observed in the Low-IAP
      group. CONCLUSIONS: Our findings demonstrate that reduction of IAP to 4 mmHg
      using the retraction method prevents the transient renal dysfunction caused by
      prolonged 12 mmHg pneumoperitoneum during LC, suggesting that the retraction
      method reduces the risk of perioperative renal dysfunction during laparoscopic
      surgery.

PMID- 9266648
TI  - Mirizzi's syndrome. Diagnostic and therapeutic controversies in the laparoscopic
      era.
AB  - BACKGROUND: Mirizzi's syndrome (MS) is an unusual cause of obstructive jaundice.
      It can mimic bile duct cancer, and the role of laparoscopic surgery is not well
      defined. The aim of this paper is to report five cases and describe the pitfalls
      encountered in its diagnosis and treatment with a laparoscopic approach. METHODS:
      From January 1992 to January 1996, five cases of MS out of 560 patients with
      gallstones prospectively treated and recorded were found (0.9%). RESULTS: There
      were two men and three women, (mean age: 54 years [30-93]). In one case diagnosis
      of bile duct carcinoma was established but surgery revealed MS. Four cases were
      approached by laparoscopy, but all of them were converted: in two, due to a
      distorted anatomy, in a third due in the difficulty of visualizing the distal end
      of the bile duct, and in the last case due to the impossibility of retrieving the
      stones. All were treated with a cholecochorrhaphy over a T tube, except one, in
      which a hepaticojejunostomy was performed. Morbidity and mortality were nil, and
      they remain asymptomatic after a mean follow-up of 19 months (3-36). CONCLUSIONS:
      MS constitutes an important laparoscopic challenge, both to clearance of duct
      stones and to the proper reconstruction of the biliary duct. A prudent policy is
      to perform a dissection trial and convert if local conditions are not clear for
      an experienced laparoscopic surgeon.

PMID- 9266649
TI  - Umbilical sinus tract with gallstone extrusion after laparoscopic
      cholecystectomy.
AB  - There are an increasing number of reports concerning complications after
      laparoscopic cholecystectomy. We report a case of persistent elevation of serum
      alkaline phosphatase and spillage of several gallstones through an
      abdominocutaneous sinus tract to the umbilicus with spontaneous resolution.

PMID- 9266650
TI  - Laparoscopic splenectomy for splenic hamartoma.
AB  - Advances in imaging techniques have made pre-operative diagnosis of splenic
      tumors possible. A case of successful laparoscopic splenectomy for splenic
      hamartoma is described here and the indications of this technique are discussed.

PMID- 9266651
TI  - Laparoscopic splenectomy in a Jehovah's Witness with profound anemia.
AB  - Open surgery in a severely anemic patient may be complicated by a substantial
      blood loss from a large incision and subsequent poor wound healing secondary to
      the anemia. We report our success in performing a splenectomy laparoscopically in
      a profoundly anemic patient. A 50-year-old white male Jehovah's Witness who was
      HIV positive was referred for splenectomy after he developed profound, worsening
      anemia secondary to hypersplenism that was refractory to medical management. His
      preoperative hemoglobin and hematocrit levels were 2.7 g/dl and 8.8%,
      respectively, but his religious beliefs precluded transfusion. A laparoscopic
      splenectomy by the posterior gastric approach was performed. The patient
      tolerated the surgery well and experienced no additional morbidity. On
      postoperative day 7, his hemoglobin and hematocrit were 6.8 g/dl and 22%,
      respectively. We conclude that laparoscopic splenectomy is an attractive
      procedure in a severely anemic patient who requires splenectomy and refuses blood
      transfusion.

PMID- 9266652
TI  - Telementoring. A practical option in surgical training.
AB  - BACKGROUND: Telemedicine offers significant advantages in bringing consulting
      support to distant colleagues. There is a shortage of surgeons trained in
      performing advanced laparoscopic operations. AIM: Our aim was to evaluate the
      role of telementoring in the training of advanced laparoscopic surgical
      procedures. METHODS: Student surgeons received a uniform training format to
      enhance their laparoscopic skills and intracorporeal suturing techniques and
      specific procedural training in laparoscopic colonic resections and Nissen
      fundoplication. Subsequently, operating rooms were equipped with three cameras.
      Telestrator (teleguidance device), instant replay (to critique errors), and CD
      ROM programs (to provide information of reference) were used as intraoperative
      educational assistance tools. In phase I, four colonic resections were performed
      with the mentor in the operating room (group A) and four colonic resections were
      performed with the mentor on the hospital grounds, but not in the operating room
      (group B). The voice and video signals were received at the mentor's location,
      using coaxial cable. In phase II, two Nissen fundoplications were performed with
      the mentors in the operating room (group C) and two Nissen fundoplications were
      performed with the mentors positioned five miles away from the operating room
      (group D), using currently existing land lines at the T-1 level. RESULTS: There
      were no differences in the performances of the surgeons and outcome of the
      operations between groups A & B and C & D. It was possible to tackle the
      intraoperative problems effectively. CONCLUSIONS: The telementoring concept is
      potentially a safe and cost-effective option for advanced training in
      laparoscopic operations. Further investigation is necessary before routine
      transcontinental patient applications are attempted.

PMID- 9266653
TI  - Exposure of the operative field in laparoscopic surgery.
AB  - Endoscopic surgery, as a result of over 90 years of investigation, has now become
      the most innovative part of general surgery; every procedure in the thoracic and
      abdominopelvic cavity, intraperitoneal or extraperitoneal, has been reviewed for
      feasibility. The basic principles in the management of surgical patients,
      however, have not changed: adequate exposure and good lighting remain important
      and may become more important with endoscopic techniques. Historical review shows
      the dependence of advances in laparoscopy upon technical development in the field
      of intraabdominal exposure as the result of two objectives: namely abdominal wall
      displacement and bowel retraction.

PMID- 9266654
TI  - Pathophysiological and clinical aspects of the CO2 pneumoperitoneum (CO2-PP).
AB  - Experimental studies demonstrated a severe cardiac load of the CO2
      pneumoperitoneum caused by an accelerated after- and a decreased preload.
      Patients displaying cardiovascular risks are therefore often rejected from
      laparoscopic surgery. Hence, the pathophysiological changes and the
      intraoperative risk of the CO2 pneumoperitoneum in high-risk cardiopulmonary
      patients (NYHA II-III, n = 15) undergoing laparoscopic cholecystectomy are
      described. The changes in cardiac after- and preload seem to be due to the
      elevated intraabdominal pressure rather than transperitoneally resorbed CO2 and
      are reversible by desufflation. In one patient conversion to open operation had
      to be performed because of a severe drop in cardiac output and right ventricle
      ejection fraction. Mixed oxygen saturation was predicting intraoperative
      worsening in this case. The described pathophysiological changes may seem to be
      well tolerated even in high-risk cardiac patients. Monitoring of hemodynamics
      should include an arterial catheter line and blood gas analyses. Pharmacologic
      interventions or pressureless laparoscopic procedures might not be necessary as
      long as laparoscopic cholecystectomy is performed.

PMID- 9266655
TI  - Systems and instruments for laparoscopic surgery without pneumoperitoneum.
AB  - The insufflation of carbon dioxide into the peritoneal cavity is a routine
      technique of abdominal exposure in laparoscopic surgery. Because of adverse
      physiological effects and technical disadvantages of the pneumoperitoneum,
      alternative methods of abdominal wall lifting have been explored recently. Two
      groups of retraction systems exist: intraabdominal lifting and subcutaneous
      lifting of the abdominal wall. Some systems require additional pneumoperitoneum,
      because the extent of intraabdominal exposure is not sufficient. Other systems
      are working completely without gas insufflation. Two systems combine abdominal
      wall lifting with pressure on the internal organs. Every method allows the use of
      standard laparoscopic instruments, which originally were designed for a regular
      pneumoperitoneum. The use of a low-pressure pneumoperitoneum in combination with
      mechanical augmentation of the peritoneal cavity reduces physiological
      disadvantages of laparoscopy. But technical advantages, such as combination of
      laparoscopic and open techniques, can be realized only without gas insufflation.
      Conventional instruments have been designed to fit the ergonomical needs of
      isopneumic laparoscopy and to be employed with simple valveless cannulae.

PMID- 9266656
TI  - Laparoscopic colectomy.

PMID- 9266657
TI  - Endoscopic right thyroid lobectomy.

PMID- 9266658
TI  - Cost comparison: disposable vs reusable instruments.

PMID- 9266660
TI  - Characterization of Salmonella dublin and Salmonella typhimurium (Copenhagen)
      isolates from cattle.
AB  - Eight Salmonella typhimurium (Copenhagen) and eight Salmonella dublin isolates
      from cattle were compared by their antibiotic resistance patterns, by their
      production of colicin, aerobactin, haemolysin and capsule, by their possession of
      transmissible R plasmids and the spvC gene, and by their ability to invade and
      replicate within cultured epithelial cells. The two groups differed in their
      antibiotic resistance profiles, with more of the host-adapted S. dublin isolates
      resistant to tetracycline than were the non-host-adapted S. typhimurium
      (Copenhagen) group, but more of the S. typhimurium (Copenhagen) isolates
      resistant to the other antibiotics tested. None of the isolates produced colicin,
      but all produced aerobactin. One isolate in each group was encapsulated. All of
      the S. typhimurium (Copenhagen) and S. dublin isolates contained plasmids, and
      all of them contained the spvC-homologous sequences. Four of the S. typhimurium
      (Copenhagen) isolates were able to transfer an R plasmid to a recipient organism
      by conjugation. One of the five S. dublin isolates, which showed resistance to
      some of the antibiotics tested, was able to transfer an R plasmid by conjugation.
      Both groups of isolates invaded cultured epithelial cells to a similar degree
      after 1 h, but the S. dublin isolates reached significantly higher levels within
      the cells than did S. typhimurium (Copenhagen) after 9 h. This ability may, in
      part, explain the association of S. dublin with more severe forms of
      salmonellosis and prolonged carrier states. Further study of the intracellular
      growth of these isolates seems warranted.

PMID- 9266661
TI  - Bacterial identity and characteristics in healthy and unhealthy respiratory
      tracts of sheep and calves.
AB  - The aim of this study was to compare different bacteriological aspects of the
      respiratory systems of healthy (H) versus unhealthy (UH) animals with respiratory
      signs. The prevalence of different bacterial species was determined in the upper
      and lower respiratory tract of H and UH Najdi sheep, Somali sheep and Holstein
      calves. The characteristics of Pasteurella spp. isolates, and the biotype of
      Pasteurella haemolytica were identified in H and UH animals, Eighteen out of 28
      (64.3%) of the identified bacterial species in the upper respiratory tract were
      more prevalent in the nasal cavities of UH Najdi and Somali sheep and Holstein
      calves with respiratory signs than in apparently healthy animals; four of the
      most prevalent bacteria in the upper respiratory system of UH sheep were
      Moraxella spp., Pseudomonas pseudomallei, Erysipelothrix spp., Pasteurella
      multocida, while three of the most prevalent bacteria in UH calves were
      Pasteurella haemolytica, Actinomyces spp., and Pseudomonas aeruginosa. The
      prevalence of six different bacterial species was greater in the lungs of UH
      animals, namely Actinomyces pyogenes, Erysipelothrix spp., P. haemolytica,
      Pasteurella ureae, Staphylococcus aureus, and Staphylococcus epidermidis, which
      could be risk factors in the complexity of the prevalent respiratory diseases of
      the animals surveyed. Of the biochemical, cytological and colonial
      characteristics studied in the identified P. haemolytica and P. multocida, two
      characters were significantly different (p < 0.05) in organisms isolated from UH
      as compared to those from H animals. These were the higher loss of haemolytic
      power by the strains of P. haemolytica and the decreased fermentation of
      trehalose by all the strains of P. multocida recovered from healthy animals. The
      only biotype of P. haemolytica isolated from H animals was biotype A, while both
      biotypes A (88.0% of the isolates) and T (12.0% of the isolates) were recovered
      from UH animals.

PMID- 9266662
TI  - The effects of crude placental extract and erythritol on growth of Chlamydia
      psittaci (ovis) in McCoy cells.

PMID- 9266663
TI  - Variations of equine urinary volatile compounds during the oestrous cycle.
AB  - Equine urine was analysed by capillary gas chromatography. The volatile profiles
      from oestrous and dioestrous samples were compared to establish any qualitative
      or quantitative difference that may have potential value in olfactory
      communication. Forty-five different volatile compounds were detected. Of these,
      17 major compounds were common to all chromatograms. The chemical profile of
      oestrous urine was distinguished by the presence of a unique peak that was not
      present in dioestrous samples. Numerous constituents exhibited endocrine
      dependence: while the concentrations of seix peaks increased at oestrus, the
      concentrations of another five peaks decreased at the same time. Since oestrous
      urine, but not dioestrous urine, has been shown to elicit sexual behaviour in the
      stallion, the unique peak, together with the peaks that were present in increased
      concentration at oestrus, may represent important chemical signals that stallions
      use to detect urinary 'oestrous odours'. Statistical analyses also indicated that
      the relative ratios (normalized peak areas) of many peaks changed significantly
      across the oestrous cycle: the rations increased in nine peaks, decreased in six
      peaks, and remained constant in two peaks at oestrus.

PMID- 9266659
TI  - Streptococcus suis: past and present.
AB  - Steptococcus suis is a Gram-positive, facultatively anaerobic coccus that has
      been implicated as the cause of a wide range of clinical disease syndromes in
      swine and other domestic animals. In swine, the disease has spread worldwide but
      is more prevalent in countries with intensive swine management practices. The
      disease syndromes caused by S. suis in swine include arthritis, meningitis,
      pneumonia, septicaemia, endocarditis, polyserositis, abortions and abscesses. S.
      suis has also been implicated in disease in humans, especially among abattoir
      workers and swine and pork handlers. In humans, S. suis type 2 can cause
      meningitis, which may result in permanent hearing loss, septicaemia, endocarditis
      and death. The pathogenic mechanism of S. suis is not well defined. Several
      virulence factors have been identified, but their roles in pathogenesis and
      disease have not been well elucidated. Much work is in progress on
      characterization of virulence factors and mechanisms, with emphasis on the
      control of the disease. Because of the non-availability of suitable
      immunoprophylaxis, control of S. suis infection has depended mainly on the use of
      antimicrobials.

PMID- 9266665
TI  - Aspects of the pharmacokinetics of doxycycline given to healthy and pneumonic
      East African dwarf goats by intramuscular injection.
AB  - The effect of experimentally induced Pasteurella haemolytica pneumonia on the
      pharmacokinetics of doxycycline (Doxycen Retard) administered intramuscularly was
      studied in seven East African dwarf goats. The study was conducted in two
      consecutive phases, separated by a washout period of four weeks. The experimental
      infection, induced by intratracheal administration of 5 ml of 10(7) to 10(9)
      cfu/ml of Pasteurella haemolytica, produced a temperature rise, depression and
      laboured breathing within 6-12 days after inoculation. The concentrations of
      doxycycline in the serum were determined by a quantitative microbiological assay
      using an agar-gel diffusion method employing Bacillus cereus var mycoides (ATCC
      11778) as the test organism, with a level of detectability of approximately 0.05
      micrograms/ml. The concentration-time curve of doxycycline in the serum after
      intramuscular injection of 20 mg/kg bodyweight of the long-acting formulation
      before and after experimental infection was adequately described by a one
      compartment open model. The maximum serum concentrations (Cmax) of doxycycline
      were lower in pneumonic goats than in healthy goats (3.87 +/- 0.52 and 5.56 +/-
      0.213 micrograms/ml, respectively), suggesting an increased distribution volume
      in the peripheral compartment. The mean +/- SEM absorption rate (ka) before
      infection (1.13 +/- 0.02 h-1) was smaller than the after infection (8.23 +/- 3.81
      h-1), but the difference was not significant. The apparent elimination half-life
      (t 1/2 beta) (24.51 +/- 0.02 h) after infection was significantly increased (p <
      0.05), while the corresponding rate constant (beta) was decreased (p < 0.01). The
      absorption half-life (t 1/2(alpha)) (0.137 +/- 0.03 h) was significantly
      decreased (p < 0.01) after infection. The distribution volume (Vd(beta)) was
      significantly increased after infection (p < 0.05). It is concluded that,
      although experimental infection had an effect on the disposition kinetics of
      doxycycline, this was not sufficiently pronounced to require alteration of the
      dosage during disease.

PMID- 9266664
TI  - A survey of anthelmintic resistance by nematodes on three sheep and two goat
      farms in Hisar (India).

PMID- 9266666
TI  - Deletion of Escherichia coli groEL is complemented by a Rhizobium leguminosarum
      groEL homologue at 37 degrees C but not at 43 degrees C.
AB  - Bacterial Cpn60 proteins (homologues to the Escherichia coli GroEL protein) are
      often examined for function by testing their ability to complement a temperature
      sensitive mutation in the E. coli groEL gene. Such tests suffer from two
      drawbacks: the Cpn600 protein may come from a strain with a lower optimum growth
      temperature than E. coli, and the requirements for successful complementation in
      E. coli are likely to be more stringent at 43 degrees C than at lower
      temperatures. Here we describe the construction of a strain of E. coli where the
      chromosomal gene for the essential molecular chaperone GroEL has been deleted,
      with GroEL being expressed from a tightly regulated plasmid borne copy of the
      gene. The deletion can be transduced into strains expressing heterologous Cpn60
      proteins, to test for complementation at any temperature. We show that a Cpn60
      protein from the bacterium Rhizobium leguminosarum can function to allow E. coli
      growth at 37 degrees C but not at 43 degrees C. By switching off the plasmid
      borne groEL gene, the effects of progressive depletion of GroEL protein from E.
      coli cells can also be monitored at any temperature.

PMID- 9266667
TI  - Physical localization and characterization of the BglI element in the genomes of
      Atlantic salmon (Salmo salar L.) and brown trout (S. trutta L.).
AB  - This work describes chromosomal localization, fine physical mapping, and
      population variation of the BglI element in the genome of Atlantic salmon (Salmo
      salar L.) and a similar sequence in the genome of brown trout (S. trutta L.).
      Results from a variety of complementary approaches, clearly demonstrate that the
      BglI element does not occur as a satellite-like repetitive DNA in these species
      but is part of the rDNA cistron as suggested by Goodier and Davidson (1993).
      Coincident hybridization of BglI clones with rDNA loci in both single and double
      probe fluorescence in situ hybridization (FISH) experiments demonstrated physical
      linkage between the BglI element and rDNA loci. Fine physical mapping by Southern
      analysis and PCR amplification showed the BglI element to be located
      approximately 1.6 kb upstream of the 18S gene. The BglI element was used to
      screen for population-specific markers by Southern analysis. Population-specific
      banding patterns were only observed in brown trout, allowing identification of
      individual populations of this species. Sequence comparisons revealed sequences
      similar to the BglI element present in the rDNA cistron of other salmonids. This
      result suggests the presence of this sequence in the genome of the salmonid
      tetraploid ancestor.

PMID- 9266668
TI  - Analysis of the alcABC operon encoding alcaligin biosynthesis enzymes in
      Bordetella bronchiseptica.
AB  - We previously cloned a B. bronchiseptica (Bb) genomic DNA fragment that
      complements a Bb alcaligin biosynthesis mutant, and reported the identification
      of a gene, alcA, with predicted protein sequence similarity to siderophore
      biosynthesis enzymes from other organisms. In the present study we show that
      further nt sequencing of this region revealed two open reading frames (ORFs) 3'
      to alcA that encode putative proteins AlcB and AlcC, with significant sequence
      similarity to the aerobactin biosynthesis enzymes IucB and IucC, respectively. RT
      PCR analysis indicated that the three ORFs are encoded on a single transcript,
      and that this operon is repressed at the transcriptional level by Fe. Primer
      extension analysis placed the transcriptional start point (tsp) 35 nt from the 5'
      end of the Fur consensus sequence and 188 nt from the putative start of
      translation of AlcA.

PMID- 9266669
TI  - Sequencing and phylogenetic analysis of the spoIIA operon from diverse Bacillus
      and Paenibacillus species.
AB  - In order to clone the spoIIA operon from three different Bacillus and
      Paenibacillus species, we designed two sets of PCR primers based on three
      previously published Bacillus spoIIA sequences. One set of primers corresponded
      to the C-terminal region of SpoIIAB and a region near the middle of SpoIIAC.
      These primers were used to amplify the corresponding region of spoIIA from
      Bacillus stearothermophilus and Paenibacillus polymyxa (previously called
      Bacillus polymyxa [see Ash, C., Priest, F.G., Collins, M.D., 1993. Molecular
      identification of ribosomal-RNA group 3 bacilli using a PCR probe test - proposal
      for the creation of a new genus Paenibacillus. Antonie van Leeuwenhoek Int. J.
      Gen. Mol. Microbiol. 64, 253-260]. The other set of primers, corresponding to an
      N-terminal and a C-terminal region of SpoIIAC, was used for B. sphaericus. The
      PCR products were used as probes for Southern blotting of homologous chromosomal
      DNA. DNA corresponding to spoIIA from the three organisms was identified by
      screening chromosomal DNA libraries, and cloned. Sequence analysis showed that
      all spoIIA sequences were conserved, but conservation was strongest in SpoIIAC
      and least strong in SpoIIAA. In the promoter the -35 region was conserved well
      but the -10 region rather poorly. Within the proteins, certain regions were
      particularly strongly conserved, suggesting that they are essential to the
      function of the protein. Phylogenetic analysis of spoIIA suggested that B.
      stearothermophilus is close to B. subtilis and B. licheniformis, but that P.
      polymyxa and B. sphaericus are remote from B. subtilis.

PMID- 9266670
TI  - Expression vectors for the introduction of highly diverged sequences into the six
      complementarity-determining regions of an antibody.
AB  - We prepared three kinds of phagemid vector that permit the simultaneous
      introduction of highly diverged sequences into six complementarity-determining
      regions (CDRs) of an antibody (Ab) by the polymerase chain reaction (PCR) with
      degenerate oligodeoxynucleotide (oligo) primers. The phages expressed either the
      Fv, single-chain Fv (sc Fv) or Fab form of an Ab fused with a half-molecule of
      cpIII on the surface of M13 phage. A phage-display library, composed of 2 x 10(8)
      independent clones, was constructed; the phages that were specific for hen egg
      white lysozyme (HEL) were selected by three rounds of panning; and 20 clones were
      isolated. The isolated clones consisted of 17 different clones. Among them, 16
      clones expressed proteins that were able to bind to HEL. The association
      constants for binding of the encoded proteins to HEL ranged from 1.48 x 10(6) to
      7.71 x 10(6)/M. These vectors allowed us to prepare many libraries of artificial
      Ab in which the sequences of six CDRs were very different and reflected the
      artificial sequences that had been designed for the degenerate oligo that we used
      as primers for PCR. The libraries should be also useful for the analysis of
      relationships between the sequences of the CDRs and antigen (Ag) specificity.

PMID- 9266672
TI  - The 239AB gene on chromosome 22: a novel member of an ancient gene family.
AB  - A novel family of genes expressed in human brain has recently been identified.
      Gene 239FB, transcribed extensively in fetal brain, was isolated from the
      chromosome 11p13 region associated with mental retardation component of the WAGR
      (Wilms tumor, aniridia, genitourinary anomalies, mental retardation) syndrome.
      This report presents a cDNA sequence and expression profile of a related gene,
      239AB, isolated from adult brain library, that was mapped to chromosome 22. While
      similar in structure, the two genes differ in their expression pattern and may
      have different roles in central nervous system development and function. In
      contrast to the 239FB, which is expressed predominantly in fetal brain, the 239AB
      gene is transcribed in adult tissues. Both human genes encode novel proteins of
      unknown function that are highly conserved from Caenorhabditis elegans to birds
      and mammals. Phylogenetic analysis suggested that the two lineages of the ancient
      gene family represented by 239FB and 239AB have been in existence prior to the
      emergence of modern animals.

PMID- 9266671
TI  - Structure and analysis of the transducin beta3-subunit gene, a candidate for
      inherited cone degeneration (cd) in the dog.
AB  - The cDNA for the beta3-subunit of cone-specific transducin (Tbeta3) was cloned
      and characterized from wild type dogs, and used in linkage studies as a candidate
      gene for cone degeneration. Sequence analysis of the Tbeta3 cDNA revealed an open
      reading frame of 1020 bp, potentially coding for a protein of 340 amino acids
      (aa). The deduced aa sequence of canine Tbeta3 shares 97% identity with the
      previously identified human Tbeta3, and 82% identity with bovine rod-specific
      transducin (Tbeta1). RT-PCR and sequencing of the amplified products demonstrated
      that the retinal canine Tbeta3 gene is expressed in two different transcripts
      which can be generated by alternative splicing of the intron in the 3'
      untranslated region (UTR). The short and the long mRNAs differ in the length of
      their 3'-UTR by 456 nt. We have also determined the genomic organization of the
      canine Tbeta3 gene; it consists of ten exons and the first exon is in the 5'-UTR.
      The cDNA encoding Tbeta3 from cd-affected dogs was also cloned and sequenced. We
      found no differences at the nucleotide level between the cDNAs isolated from
      normal and diseased retinas. The level of transcription of Tbeta3 mRNA in the cd
      dog retina appeared to be normal. Linkage analysis of a crossbred informative
      pedigree showed five obligate recombinants out of nine informative offspring.
      These results suggest that Tbeta3 is not a candidate gene for the cone
      degeneration of the cd mutant.

PMID- 9266673
TI  - Structure and expression of the chicken calmodulin I gene.
AB  - The chicken calmodulin I (CaMI) gene has been isolated and characterized on the
      level of cDNA and genomic DNA. The deduced amino acid (aa) sequence is identical
      to the one of chicken CaMII which consists of 148 aa. The CaMI gene contains six
      exons. Its intron/exon organization is identical to that of the chicken CaMII and
      the CaMI and CaMIII genes of rat and human. Expression of the CaMI gene was
      detected in all chicken tissues examined, although at varying levels. The gene is
      transcribed into four mRNAs of 0.8, 1.4, 1.7 and 4.4 kb as determined by Northern
      blot analysis. Our results demonstrate that the "multigene-one-protein" principle
      of CaM synthesis is not only applicable to mammals whose CaM is encoded by three
      different genes, but also to chickens.

PMID- 9266674
TI  - Sequence similarities between large subunit ribosomal RNA gene intervening
      sequences from different Helicobacter species.
AB  - When the 23S rRNA genes from several Helicobacter species were amplified by PCR
      and compared with similar amplicons derived from H. pylori, they were seen to be
      enlarged in size. Sequencing of these enlarged genes from H. mustelae, H. canis
      (two strains) and H. muridarum identified insertions of novel sequence
      (intervening sequences, IVSs) sized between 93 and 377 bp located at nt 545, in
      place of an 8-nt sequence in the conventionally sized H. pylori gene. These IVSs
      were not present elsewhere in the genome. All strains with such IVSs lacked
      intact 23S rRNA which was replaced by two fragment whose sizes were consistent
      with cleavage at either side of the particular IVS. The predicted secondary
      structures of the four IVSs were characterised by base pairing at the 5' and 3'
      ends to form a stem. The four IVSs exhibited significant sequence inter
      relationships. Further relationships were also observed between them and similar
      elements in both small and large subunit rRNA genes of other Helicobacter and
      Campylobacter species. Alignment of each IVS with the other such elements
      identified blocks of related sequence consistent with insertion/deletion events,
      indicating possible evolutionary relationships.

PMID- 9266675
TI  - A direct method for the chromosomal assignment of DNA markers in Leishmania.
AB  - A simple method for the chromosomal assignment of any DNA marker would be an
      important tool for the ongoing project to map the genome of the protozoan
      parasite Leishmania. The Leishmania chromosomes enter pulsed field gel
      electrophoresis (PFGE) gels under current electrophoretic conditions, but their
      direct identification in a given strain is hampered by their stacking in a few
      chromosomal bands, and by the very frequent size variations of the same
      chromosome among parasite strains. To overcome these problems. we determined the
      complete karyotypes of 12 Old World Leishmania cloned strains. This enabled us to
      select three of these strains that display great chromosome size polymorphisms,
      such that every chromosome can be individualized by a specific pattern after
      hybridization onto these three karyotypes. The complete resolution of the genomes
      of these three strains can be carried out with only three electrophoretic
      conditions. This makes a series of three blots sufficient for the assignment of
      any new marker on a particular Leishmania chromosome.

PMID- 9266676
TI  - High frequency transposition of the Tn5 derivative Tn5493 in Streptomyces
      lividans.
AB  - The mini-Tn5 derivative transposon Tn5493 transposes at a frequency as high as 3%
      in the Gram-positive bacterium Streptomyces lividans. The use of a thiostrepton
      resistance gene and a temperature-sensitive delivery system carrying the
      transposase gene allows an easy selection for stable transposition events.
      Insertions into the S. lividans genome seem to be fairly random, as shown by
      Southern blot and pulsed-field gel electrophoresis (PFGE). Transpositions were
      easily mapped by PFGE using the restriction sites of rare-cutting enzymes present
      in the transposon. Because of its characteristics, Tn5493 is a promising tool for
      genetic and molecular analysis and manipulation of the antibiotic-producing
      streptomycetes.

PMID- 9266677
TI  - Complementary oligonucleotides and the origin of the mammalian involucrin gene.
AB  - A large portion of the consensus sequence of four mammalian involucrin genes
      comprises four pairs of complementary oligonucleotides. One of the
      oligonucleotides in each pair is rich in purines and the other in pyrimidines.
      The perfect complementarity of a number of pairs apparently resulted from a
      concerted single nucleotide substitution in each pairing oligonucleotide from
      their respective consensus. This suggests that one member of the pair was derived
      from the other member of the same pair by a template-dependent replication
      mechanism. Such a replication mechanism differs from the one that creates tandem
      repeats by producing short complementary sequence on the same strand of DNA.

PMID- 9266678
TI  - Human growth hormone receptor: cloning and expression of the full-length
      complementary DNA after site-directed inactivation of a cryptic bacterial
      promoter.
AB  - Growth hormone receptor is a cytokine-type receptor which is required for normal
      somatic growth and for numerous metabolic processes. Its complementary DNA (cDNA)
      has been isolated in various species leading to intensive studies to elucidate
      the mechanism of action of the growth hormone. However, serious difficulties have
      been reported in cloning in Escherichia coli, an intact full-length human cDNA.
      In this study, the cDNA is shown to contain a cryptic bacterial promoter driving
      inappropriate expression of a part of human growth hormone (hGH) receptor which
      is toxic for E. coli growth. Identification of this promoter and its inactivation
      by changing only one nucleotide led us to obtain stable bacterial clones
      containing a high copy number of full-length coding sequences. This molecular
      clone was used in a baculovirus/insect cell system to produce large amounts of
      glycosylated recombinant receptor. Binding studies with 125I-labelled hGH
      revealed an affinity constant of 2.8 x 10(9) M(-1), similar to that reported for
      the native liver receptor. This report described a general method of cloning
      which could be applied to similar unclonable cDNA fragments.

PMID- 9266679
TI  - A compositional map of the cen-q21 region of human chromosome 21.
AB  - A compositional map of the centromere and of the subcentromeric region of the
      long arm of human chromosome 21 was established by determining the GC levels (GC
      is the molar fraction of guanine+cytosine in DNA) of 11 YACs (yeast artificial
      chromosomes) covering this 13-14 Mb region which extends from the alpha-satellite
      sequences of the C(entromeric) band q11.1, through R(everse) band q11.2, to the
      proximal part of G(iemsa) band q21. The entire region is made up of GC-poor, or
      L, isochores with only one GC-rich H1 isochore, at least 2 Mb in size, located in
      band q21. The almost identical GC levels of the centromeric alpha-satellite
      repeats (38.5%), of R band q11.2 (39%), and of G bands (38-40%) provide a direct
      demonstration that base composition cannot be the only cause of the cytogenetic
      differences between C, G, and the majority of R bands, namely the H3- R bands
      (which do not contain the GC-richest H3 isochores). The results obtained also
      show that isochores may be as long as 6 Mb, at least in the GC-poor regions of
      the genome, and support previous observations suggesting that YACs from isochore
      borders are unstable and/or difficult to clone. Genes and CpG islands are very
      rare in the GC-poor region investigated, as expected from the fact that their
      concentration is proportional to the GC levels of the isochores in which they are
      contained.

PMID- 9266680
TI  - Serum-dependent and cell cycle-dependent expression from a cytomegalovirus-based
      mammalian expression vector.
AB  - Cytomegalovirus-based mammalian expression vectors are widely used to drive the
      expression of transfected genes in cultured cells. Immunofluorescent staining of
      the WT1 protein in 3T3 and 293 cell clones, stably transfected with a
      cyomegalovirus (CMV) expression vector carrying a cDNA coding for the tumour
      suppressor protein WT1, showed extreme cell to cell variation in the amount of
      recombinant protein expressed, indicative of cell cycle dependence. This was
      investigated further by Western blot and FACS analysis which showed that WT1
      protein expression was highest in S phase and almost absent in G0/G1. Northern
      blot analysis of cell clones expressing sense or antisense WT1 cDNAs regulated by
      the CMV promoter/enhancer showed that RNA expression was also cell cycle
      dependent. Western blotting of cells expressing a luciferase reporter gene driven
      by the CMV promoter/enhancer also showed apparent cell cycle-dependent
      expression. We further demonstrated that the expression of these gene constructs
      was serum responsive with a 10-fold increase in expression occurring 2 h after
      the addition of serum. These results show that the CMV promoter/enhancer system
      varied in its response to serum and the cell cycle state. Therefore, care must be
      taken when interpreting any phenotypic alterations (or lack of them) produced in
      cells transfected with CMV-based expression vectors.

PMID- 9266681
TI  - Ribosomal RNA synthesis in Streptomyces lividans under heat shock conditions.
AB  - Clones containing rRNA genes were isolated from a gene library of Streptomyces
      lividans when RNA produced under heat shock conditions was used as a probe. Two
      of the clones carried entire rRNA operons rrnA and rrnF, respectively, the
      expression of both operons being under the control of four different promoters.
      At least two of the promoters were fully functional when the temperature
      increased from 30 to 45 degrees C, ensuring transcription of the rRNA genes under
      the heat shock. A third clone carried a partial rRNA operon in which expression
      was controlled by a main promoter that was functional at both 30 and 45 degrees
      C.

PMID- 9266682
TI  - Cloning and sequencing of the hrcA gene of Bacillus stearothermophilus.
AB  - We report on cloning and sequencing of a 2.0-kb PCR fragment of chromosomal DNA
      from thermophilic Bacillus stearothermophilus carrying the complete hrcA gene. In
      addition, this amplicon contains the 3' end of an open reading frame exhibiting
      significant homology to the hemN gene of Bacillus subtilis (Bs) and other
      bacterial species. The hrcA gene could complement an Bs hrcA deletion mutant by
      repressing expression of class I heat shock (HS) genes. Furthermore, we could
      show that the HrcA protein derived from the thermophilic microorganism responds
      to HS in a similar way as reported for the Bs HrcA protein.

PMID- 9266683
TI  - Cloning and expression of the Borrelia burgdorferi lon gene.
AB  - The ATP-dependent protease Lon (La) of Escherichia coli degrades abnormal
      proteins and is involved in the regulation of capsular polysaccharide synthesis.
      In addition, mutations in the E. coli lon gene suppress temperature-sensitive
      mutations in other genes. The lon gene of Borrelia burgdorferi, encoding a
      homolog of the Lon protease, has been cloned and sequenced. The gene encodes a
      protein of 806 amino acids. The deduced amino acid sequence of the B. burgdorferi
      Lon protease shares substantial sequence identity with those of other known Lon
      proteases. The transcription start point of the B. burgdorferi lon gene was
      identified by primer extension analysis and the potential promoter did not show
      similarities to the consensus heat-shock promoter in E. coli. The 5'-end of the
      B. burgdorferi lon gene appears to suppress the temperature-sensitive phenotype
      of an E. coli lpxA mutant.

PMID- 9266684
TI  - The majority of long non-stop reading frames on the antisense strand can be
      explained by biased codon usage.
AB  - In recent studies it has been suggested that long reading frames on the antisense
      strand of open reading frames (ORFs) are more frequent than expected. The
      vertebrate DNA database was searched for long (greater than 900 bp) antisense non
      stop reading frames (aNRFs) that overlap known coding regions. The sequences
      obtained were predominantly positioned in DNA with a high usage of G or C in the
      third codon position of the sense ORF. The major class of sequences revealed by
      the search was that of the heat-shock protein 70 kDa (Hsp70) family. A long Hsp70
      aNRF was found in many Hsp70 sequences and occurred in species as diverse as
      fish, flies, fungi and bacteria. The role of codon usage bias was analysed both
      in the specific case of the Hsp70 genes and in a general species-wide context.
      The data obtained showed that even the very long aNRFs present in the Hsp70
      family could be explained by codon usage bias on the sense strand. Codon usage
      bias is determined by GC content at the third codon position of the sense ORF
      and, in some species, by a high expression level of the gene in question. Such an
      explanation for the occurrence of long aNRFs cannot exclude that some aNRFs are
      transcribed and translated.

PMID- 9266685
TI  - The role of the cap structure in RNA processing and nuclear export.
AB  - The cap structure that is characteristic of all polymerase-II-transcribed RNAs
      has been shown to play an important role in many aspects of RNA metabolism
      including RNA processing, RNA nuclear transport, and translation initiation. The
      effects of the cap structure on these different processes is mediated by proteins
      that recognise and bind to it, and are therefore generically called cap-binding
      proteins. For example, the cap-binding protein eIF4E, in a complex with other
      proteins, mediates the effect of the cap on the initiation of translation. EIF-4E
      is predominantly localised in the cytoplasm. In the last five years, it has been
      demonstrated that a second cap-binding protein complex, which is mainly localised
      in the nucleus, mediates the stimulatory effects of the cap in nuclear processes
      such as pre-mRNA splicing, RNA 3'-end formation, and RNA nuclear export. The
      purpose of this review is to summarise our current knowledge on the role of the
      cap structure and of the cap-binding protein complex in nuclear RNA metabolism
      and present evidence that at least some processes may be coupled in vivo.

PMID- 9266686
TI  - Isolation and properties of Drosophila melanogaster ferritin--molecular cloning
      of a cDNA that encodes one subunit, and localization of the gene on the third
      chromosome.
AB  - Ferritin was purified from iron-fed Drosophila melanogaster extracts by
      centrifugation in a gradient of potassium bromide. On polyacrylamide gel
      electrophoresis, the product showed two protein bands corresponding to the
      ferritin monomer and dimer. Electrophoresis following dissociation with SDS and 2
      mercaptoethanol revealed three strong bands of approximately 25, 26, and 28 kDa.
      N-terminal amino acid sequences were identical for the 25-kDa and 26-kDa
      subunits, but different for the 28-kDa subunit. Conserved ferritin PCR primers
      were used to amplify a 360-bp cDNA product, which was used to isolate a clone
      from a D. melanogaster cDNA library that contained the complete coding sequence
      for a ferritin subunit. Additional 5' sequence obtained by the RACE method
      revealed the presence of a putative iron regulatory element. The PCR product was
      also used to locate the position of the ferritin subunit gene at region 99F on
      the right arm of the third chromosome. The deduced amino acid sequence of the D.
      melanogaster ferritin subunit contained a signal sequence and resembled most
      closely ferritin of the mosquito Aedes aegypti. The evolution of ferritin
      sequences is discussed.

PMID- 9266687
TI  - Structural characterization of four genetic variants of human serum albumin
      associated with alloalbuminemia in Italy.
AB  - A long-term electrophoretic survey on plasma proteins, which was carried out in
      several clinical laboratories in Italy, identified 28 different genetic variants
      of human serum albumin and four cases of analbuminemia. We have previously
      characterized 16 point mutations, 3 C-terminal mutants, and the genetic defects
      in two analbuminemic subjects. Here, we report the molecular defects of four
      alloalbumins that have been characterized by protein structural analysis. Of
      these, three represent new single-point mutations: albumins Tregasio, Val122-
      >Glu, Bergamo, Asp314-->Gly, and Maddaloni, Val533-->Met. The fourth, albumin
      Besana Brianza, has the same Asp494-->Asn mutation that introduces a
      glycosylation site which has been previously reported in a variant from New
      Zealand, albumin Casebrook. However, in contrast to albumin Casebrook, albumin
      Besana Brianza is only partially glycosylated and the oligosaccharide is
      heterogeneous, consisting of a biantennary complex type N-glycan with either two
      or one sialic acid residue(s) on the antennae. Both albumin Maddaloni and Besana
      Brianza represent mutations at hypermutable CpG dinucleotide sites; albumin
      Maddaloni is a mutant that does not involve a charged amino acid.

PMID- 9266688
TI  - Substrate binding and catalysis by L-arginine:glycine amidinotransferase--a
      mutagenesis and crystallographic study.
AB  - L-Arginine:glycine amidinotransferase catalyzes the committed step in the
      biosynthesis of creatine. Eight active-site mutants, D170N, D254N, H303V, D305A,
      R322E, S355A, C407S, and C410A of recombinant human L-arginine:glycine
      amidinotransferase were prepared by site-directed mutagenesis and enzymatically
      characterized. The crystal structures of the three mutants D170N, D254N, and
      C407S have been determined at 0.28-nm, 0.29-nm and 0.236-nm resolution,
      respectively. The mutation of active-site residues which are involved in
      substrate-binding yielded inactive mutants. Substitution of Asp254, which is not
      directly involved in substrate binding but is thought to transfer protons in
      concert with the His303 imidazole group, results in a strongly (2000-fold)
      reduced activity. However, the substitution of Cys410, a residue near the active
      site but not involved in catalysis or substrate binding, by Ala does not change
      the kinetic properties with respect to the wild-type enzyme. The loss of
      enzymatic activity of the D170N, D254N, C407S and likely all other mutants is
      solely due to the inserted point mutations, affecting substrate binding or
      transition-state stabilization, and not due to major conformational
      rearrangements of the protein. These results show that a His-Asp pair on one side
      of the substrate and a Cys on the other side are key residues for activity and
      are part of a disjoint triad. The imidazole ring of the His is proposed to act as
      a general acid/general base during catalysis whereas the Cys acts as a
      nucleophile analogous to Cys25 of papain-like cysteine proteinases.

PMID- 9266689
TI  - Partial identification of the Zn2+-binding sites in factor XII and its activation
      derivatives.
AB  - With the purpose of identifying the Zn2+-binding sites in factor XII, the effect
      of chemical modification of His, Glu and Asp residues, amino acids known to
      participate in the catalytic coordination binding of Zn2+ in a number of Zn2+
      binding proteins, was analysed. The number of modifiable His residues in factor
      XII and alpha-factor XIIa was 16.0+/-0.7 and 17.3+/-0.7, respectively. When
      factor XII/alpha-factor XIIa was incubated with saturating concentrations of Zn2+
      before the diethylpyrocarbonate modification of the His residues, these numbers
      were reduced to 6.3+/-0.1 and 8.21+/-0.5, indicating that ten and nine His
      residues, respectively, are involved in the binding. Analysis of the Zn2+-binding
      capacity of factor XII, alpha-factor XIIa and beta-factor XIIa showed that while
      factor XII contains four Zn2+-binding sites, alpha-factor XIIa had only three and
      beta-factor XIIa had none. Modification of the His residues resulted in a
      complete loss of Zn2+-binding while Asp/Glu modification resulted in loss of two
      and one Zn2+-binding sites in factor XII and alpha-factor XIIa, respectively.
      This suggests that two of the four sites in factor XII contain His residues,
      exclusively, while the two others are comprised of two His residues and one
      Asp/Glu residue. One of the latter is lost when factor XII is activated to alpha
      factor XIIa. Two of the sites are suggested to be located at positions His40
      His44 and His78-His82. The location of the remaining two sites are reduced to
      four possible positions.

PMID- 9266690
TI  - Transcriptional regulatory region for expression of the rat ATP citrate-lyase
      gene.
AB  - We previously mapped the sequences responsive to insulin/glucose stimulation and
      polyunsaturated fatty-acid suppression in the proximal promoter region between
      positions -104 and -20 of the ATP citrate-lyase (ACL) gene [Fukuda, H., Iritani,
      N., Katsurada, A. & Noguchi, T. (1996) FEBS Lett. 380, 204-207]. To investigate
      further the regulatory DNA sequences required for stimulation and suppression of
      this gene, primary cultured hepatocytes were transfected with plasmids containing
      the 5'-flanking sequences of the rat ACL gene fused to the chloramphenicol
      acetyltransferase (CAT) gene. When two copies of the sequences spanning -64 to 
      41 (linked to ACLcat20) were used for transfection, CAT activity significantly
      increased in response to insulin/glucose treatment. This increase was inhibited
      by addition of polyunsaturated fatty acid. Mutational analysis of this region
      showed that sequences between -55 and -51 are essential for recognition and
      interaction with trans-acting factors. Gel mobility shift assays using the
      sequence from -64 to -41 as a probe revealed nuclear factor(s) from rat liver
      that specifically complexed with the sequences. In addition, by antibody
      supershift assays, we have detected the binding of the transcriptional factor Sp1
      at the G+C-rich region located within -64 to -41 of the ACL promoter. On the
      other hand, the formations of DNA-protein complexes with Sp1 binding site or ACL(
      64 to -41) were decreased in rats fed a high-carbohydrate diet in comparison with
      those in rats fasted or fed a polyunsaturated fatty-acid-rich diet.
      Cotransfection studies in rat hepatocytes, with the Sp1 expression vector and
      ACLcat constructs, showed the inactivation of the promoter. These results
      demonstrated that the region from -64 to -41 of the ACL gene was responsible for
      stimulation due to insulin/glucose, the stimulation was suppressed by
      polyunsaturated fatty acid, and Sp1 may be involved in the regulation.

PMID- 9266691
TI  - Regulation of human interstitial collagenase (matrix metalloproteinase-1)
      promoter activity by fibroblast growth factor.
AB  - Basic fibroblast growth factor (bFGF) is a pleiotropic factor that is implicated
      in tissue remodeling. The growth factor is capable of up-regulating the
      expression of the interstitial collagenase (matrix metalloproteinase-1 or MMP-1)
      gene. In this study, the full-length human MMP-1 promoter, spanning 4.3 kb, was
      sequenced and the regulatory control of its activity by bFGF was examined in
      NIH3T3 fibroblasts. Several regulatory sequences, including five activator
      protein-1 (AP-1), five activator protein-2 (AP-2), five glucocorticoid-response
      elements and multiple ets/polyoma enhancer-binding 3 elements, were identified.
      Deletion constructs were prepared and transiently transfected into fibroblast
      cultures incubated with and without bFGF. The results showed that bFGF enhanced
      the activity of the deletion promoter fragments and the full-length MMP-1
      promoter by sixfold or more in the cell cultures. Stimulation of the MMP-1
      promoter activity by bFGF was reflected in substantial increase of the
      collagenase mRNA levels. A bFGF-responsive element appeared to be the AP-1
      consensus sequence. Mutation of the first AP-1 site resulted in major reduction
      of the basal level of the MMP-1 promoter activity, supporting the notion that the
      AP-1 consensus sequence is essential for the constitutive expression of the MMP-1
      gene. Furthermore, bFGF induction of the activity of the promoter constructs
      containing a mutant AP-1 site was essentially absent, suggesting that the
      regulatory element is necessary for the induction of the promoter activity by the
      growth factor. Thus, bFGF up-regulates MMP-1 gene expression in NIH3T3
      fibroblasts via induction of its promoter activity that is dependent on an AP-1
      consensus sequence.

PMID- 9266692
TI  - Immunological localization and tissue distribution of
      alkyldihydroxyacetonephosphate synthase and deficiency of the enzyme in
      peroxisomal disorders.
AB  - Alkyldihydroxyacetonephosphate synthase (alkylglycerone-phosphate synthase) is a
      peroxisomal enzyme involved in ether phospholipid biosynthesis. The recent
      cloning of the cDNA encoding this enzyme from guinea pig liver enabled the
      raising of specific antisera against this enzyme. Both a synthetic peptide
      corresponding to a predicted epitope and a recombinant protein expressed in
      Escherichia coli were used for that purpose. Using western blot techniques, the
      solubilization of the enzyme from the peroxisomal membrane by Triton X-100 in the
      presence of salt was confirmed. Neutral hydroxylamine treatment of peroxisomes
      resulted in almost no release of the protein from the membrane. The complete
      polypeptide chain of the enzyme was resistant to proteolysis by trypsin when
      intact peroxisomes were studied. Carbonate treatment released
      alkyldihydroxyacetonephosphate synthase from the membrane indicating that the
      enzyme is not an integral membrane protein. This idea is in accord with the
      absence of a clear hydrophobic transmembrane domain in the deduced amino acid
      sequence of the enzyme. Alkyldihydroxyacetonephosphate synthase, as well as its
      mRNA, could be detected in all five guinea pig tissues examined. When using the
      antiserum against guinea pig recombinant alkyldihydroxyacetonephosphate synthase,
      a cross-reactive protein was detected in a human liver homogenate that runs at a
      slightly higher molecular mass. The absence of this band in liver of Zellweger
      syndrome and Rhizomelic chondrodysplasia punctata patients provides strong
      evidence that it represents the human homolog of this enzyme.

PMID- 9266693
TI  - Post-translational activation of non-homologous DNA end-joining in Xenopus oocyte
      extracts.
AB  - We have analysed the recircularisation of plasmid DNA, cut with two different
      endonucleases to generate non-homologous DNA ends, in extracts of unfertilised
      eggs and oocytes of Xenopus. We found that the capacity to join non-homologous
      DNA ends, generating diagnostic covalently closed monomer circles, appeared
      during oocyte maturation at the time of germinal vesicle breakdown. This enzyme
      function was post-translationally activated in oocyte extracts incubated with
      unfertilised egg extract containing active cdc2/cyclin B, or by incubation with
      purified cdc2/cyclin B. Dephosphorylation of egg proteins by alkaline phosphatase
      inhibited the ability to join non-homologous DNA ends. We show that most linear
      non-homologous DNA ends repaired to form closed-circular supercoiled monomers,
      are joined without loss of nucleotides. Following partial purification, the
      activity was inhibited by inhibitors of poly(ADP-Rib) polymerase, an enzyme that
      is inactive in oocytes, but phosphorylated and activated during maturation.
      Competitive inhibition of poly(ADP-Rib) polymerase by > 50 microM 3
      aminobenzamide prevented the joining of both matched and non-homologous DNA ends.
      We conclude that post-translational phosphorylation provides one route by which
      end-joining of non-homologous DNA can be regulated.

PMID- 9266694
TI  - The pipecolate-incorporating enzyme for the biosynthesis of the immunosuppressant
      rapamycin--nucleotide sequence analysis, disruption and heterologous expression
      of rapP from Streptomyces hygroscopicus.
AB  - An open reading frame (rapP) encoding the putative pipecolate-incorporating
      enzyme (PIE) has been identified in the gene cluster for the biosynthesis of
      rapamycin in Streptomyces hygroscopicus. Conserved amino acid sequence motifs for
      ATP binding, ATP hydrolysis, adenylate formation, and 4'-phosphopantetheine
      attachment were identified by sequence comparison with authentic peptide
      synthetases. Disruption of rapP by phage insertion abolished rapamycin production
      in S. hygroscopicus, and the production of the antibiotic was specifically
      restored upon loss of the inserted phage by a second recombination event. rapP
      was expressed in both Escherichia coli and Streptomyces coelicolor, and
      recombinant PIE was purified to homogeneity from both hosts. Although low-level
      incorporation of [14C]beta-alanine into recombinant PIE isolated from E. coli was
      detected, formation of the covalent acylenzyme intermediate could only be shown
      with the PIE from S. coelicolor, suggesting that while the recombinant PIE from
      S. coelicolor was phosphopantetheinylated, only a minor proportion of the
      recombinant enzyme from E. coli was post-translationally modified.

PMID- 9266695
TI  - An angiogenic protein from bovine serum and milk--purification and primary
      structure of angiogenin-2.
AB  - Bovine serum and milk contain a basic angiogenic protein that binds tightly to
      placental ribonuclease inhibitor. It was purified from both sources by ion
      exchange and reversed-phase chromatographies. Its amino acid sequence revealed
      that it is a member of the ribonuclease superfamily. It contains 123 amino acids
      in a single polypeptide chain, is cross-linked by three disulfide bonds, is
      glycosylated at Asn33, and is 57% identical to bovine angiogenin. The amino
      terminal and carboxyl-terminal residues are pyroglutamic acid and proline,
      respectively. The protein has ribonucleolytic activity that is similar to, but
      somewhat lower than, that of bovine angiogenin, i.e. very low relative to RNase.
      It is angiogenically potent on chicken chorioallantoic membrane, but less so than
      angiogenin. The sequence and activities demonstrate that this protein is a
      second, distinct, member of the angiogenin sub-family of pancreatic
      ribonucleases, and is referred to as angiogenin-2.

PMID- 9266696
TI  - The solution structure and activity of caerin 1.1, an antimicrobial peptide from
      the Australian green tree frog, Litoria splendida.
AB  - Caerin 1.1 is one of the major antimicrobial peptides isolated from the skin of
      the Australian green tree frog, Litoria splendida. Two-dimensional 1H-1H and 1H
      13C NMR spectroscopy in trifluoroethanol/H2O (50:50, by vol.) have been used to
      assign the 1H and 13C-NMR spectra of this 25-amino-acid peptide. From an
      examination of these data, and using distance geometry and molecular dynamics
      calculations, the solution conformation of caerin 1.1 has been determined. The
      peptide adopts two well-defined helices from Leu2 to Lys11 and from Val17 to
      His24 separated by a region of less-defined helicity and greater flexibility.
      Overall, the peptide has a distinct amphipathic charge distribution. The solution
      structure of caerin 1.1 is compared with activity data against a variety of micro
      organisms for the parent peptide and some naturally occurring and synthetic
      variants of caerin 1.1. The structural and activity data are consistent with
      caerin 1.1 interacting with membranes in a similar manner to other antimicrobial
      peptides, i.e. via a carpet-like mechanism whereby the individual peptides
      aggregate in a helical manner and orient themselves parallel to the membrane in a
      sheet-like arrangement [Shai, Y. (1995) Trends Biochem. Sci. 20, 460-464].

PMID- 9266697
TI  - Cloning and expression of cDNA for a human Gal(beta1-3)GalNAc alpha2,3
      sialyltransferase from the CEM T-cell line.
AB  - Complementary DNA encoding a human Gal(beta1-3)GalNAc alpha2,3-sialyltransferase
      type II (hST3Gal II) was cloned from a CEM T-cell cDNA library using a 23-base
      oligonucleotide probe. The sequence of this probe was established on the basis of
      a slightly divergent sialylmotif L that was obtained by polymerase chain reaction
      with degenerate oligonucleotide primers based on the conserved sialylmotif L of
      mammalian Gal(beta1-3)GalNAc alpha2,3-sialyltransferases. It was thus confirmed
      that a short oligonucleotide probe may be sensitive and highly specific. The
      nucleotide and amino acid sequences of hST3Gal II show, respectively, 56.3% and
      49.3% similarity to hST3Gal I [Kitagawa, H. & Paulson, J. C. (1994) J. Biol.
      Chem. 269, 17872-17878] and 88.1% and 93.7% similarity to murine ST3Gal II [Lee,
      Y. C., Kojima, N., Wada, E., Kurosawa, N., Nakaoka, T., Hamamoto, T. & Tsuji, S.
      (1994) J. Biol. Chem. 269, 10028-10033]. hST3Gal II mRNA was highly expressed in
      heart, liver, skeletal muscle and various lymphoid tissues but not in brain and
      kidney. A soluble form of hST3Gal II expressed in COS-7 cells was tested in vitro
      for substrate specificity and kinetic properties. Asialofetuin and asialo-bovine
      submaxillary mucin appeared better substrates for hST3Gal II than for its murine
      counterpart as previously reported [Kojima, N., Lee, Y.-C., Hamamoto, T.,
      Kurosawa, N. & Tsuji, S. (1994) Biochemistry 33, 5772-5776]. In previous studies,
      we have shown hyposialylation of O-glycans attached to two major lymphocyte CD43
      and CD45 cell surface molecules in human-immunodeficiency-virus-1(HIV-1)-infected
      T-cell lines. Since comparable levels of hST3Gal I and hST3Gal II mRNA and
      enzymatic activity were observed in parental and HIV-1-infected CEM T-cell
      lysates, the sialylation defect associated with HIV infection of this cell line
      is probably due to a mechanism different from a simple altered catalytic activity
      of these sialyltransferases.

PMID- 9266698
TI  - Structural studies of the O-antigen polysaccharide from Escherichia coli O138.
AB  - The structure of the O-antigen polysaccharide from Escherichia coli O138 has been
      determined. NMR spectroscopy, together with component and methylation analyses,
      of native and reduced polysaccharide were the principal methods used. The
      sequence of the sugar residues could be determined by NOESY and heteronuclear
      multiple bond connectivity (HMBC) NMR experiments. It is concluded that the
      polysaccharide is composed of tetrasaccharide repeating units with the following
      structure: [structure: see text].

PMID- 9266699
TI  - Efflux of compatible solutes in Corynebacterium glutamicum mediated by
      osmoregulated channel activity.
AB  - Bacteria respond to hypoosmotic stress by releasing low-molecular-mass solutes in
      order to maintain constant turgor pressure. We have studied the function of
      osmoregulated channel(s) in Corynebacterium glutamicum, which are responsible for
      efflux of various solutes upon sudden decrease in osmotic pressure. The channels
      preferentially mediated efflux of compatible solutes such as glycine betaine and
      proline. The release of molecules of similar size, e.g. glutamate or lysine, was
      restricted, ATP was completely retained even after severe osmotic shock. The
      cells maintained high cytoplasmic K+ and Na+ concentrations under hypoosmotic
      shock. Several results suggest that the solute efflux is mediated by a channel
      and not by a carrier, e.g. by reversal of the glycine betaine uptake systems of
      C. glutamicum: the release of glycine betaine and proline was extremely fast
      reaching an efflux rate of 6000 micromol x min(-1) x g dm(-1) or higher; the
      efflux was not significantly influenced by addition of external transport
      substrate, e.g. glycine betaine; in spite of an extremely high chemical gradient,
      no significant efflux under isoosmolar conditions was observed; efflux of solutes
      was unchanged after full uncoupling of membrane energetics by carbonylcyanide m
      chlorophenylhydrazone (CCCP). These results indicate the presence of an
      osmoregulated channel in C. glutamicum similar to the mechanosensitive channel(s)
      of Escherichia coli. The activity of the channel did not depend on the growth
      conditions, but we observed a tight regulation on the level of activity, i.e. the
      mechanosensitive channel behaved as a perfect osmometer. By monitoring release of
      glycine betaine under slow and continuous decrease of the external osmolality, we
      observed continous efflux whithout a stepwise release of solutes. This resulted
      in a significant steady-state decrease of the membrane potential.

PMID- 9266700
TI  - Amplified expression, purification and functional reconstitution of the dipeptide
      and tripeptide transport protein of Lactococcus lactis.
AB  - Transport of hydrophilic dipeptides and tripeptides into Lactococcus lactis is
      mediated by a proton-motive-force-driven peptide-transport protein (DtpT) that
      shares similarity to eukaryotic peptide transporters, e.g. from yeasts, plants,
      and the kidney and small intestine of rabbit, man and rat. The expression level
      of DtpT protein in L. lactis was increased (20-40-fold) to approximately 10% of
      total integral membrane protein by means of a low-copy-number vector and
      selecting the appropriate growth conditions. Membrane vesicles bearing the DtpT
      His6 protein (containing a C-terminal factor-Xa cleavage site and a six-histidine
      tag) showed a Pro-Ala uptake activity that was half that of membranes containing
      the wild-type protein. The activity in the DtpT-His6 membrane vesicles increased
      at least 50% upon removal of the His6 tag from the protein. More than 95% DtpT
      was solubilized from L. lactis membranes in the presence of 1% (mass/vol.) n
      dodecyl-beta-D-maltoside, and approximately 2 mg DtpT-His6 was purified by Ni2+
      chelate affinity chromatography from 100 mg membrane protein. Purified DtpT-His6
      was reconstituted unidirectionally into detergent-saturated formed liposomes,
      which were prepared from Escherichia coli phospholipid and egg
      phosphatidylcholine; the detergent was removed by adsorption to polystyrene
      beads. The highest uptake activities were obtained when DtpT was incorporated
      into liposomes that were treated with a low amount of n-dodecyl-beta-D-maltoside
      (onset of liposome solubilization). The uptake activity could be improved by
      addition of NaCl (200 mM) and lipids (2 mg/ml) during the solubilization,
      purification and reconstitution steps.

PMID- 9266701
TI  - Metalloelastase expression in a mouse macrophage cell line--regulation by 4beta
      phorbol 12-myristate 13-acetate, lipopolysaccharide and dexamethasone.
AB  - The regulation of the expression of mouse macrophage elastase (MME) was
      investigated using the murine tumor cell line P388D1. The effects of three
      factors were studied: a phorbol ester (4beta-phorbol 12-myristate 13-acetate,
      PMA), an endotoxin (lipopolysaccharide, LPS) and a corticosteroid
      (dexamethasone). Both in situ hybridization and northern blot analysis showed
      that P388D1 cells constitutively express the MME gene. Quantification of the MME
      mRNA by northern blot analysis showed that only PMA and dexamethasone
      significantly regulate MME gene expression in a time-dependent and dose-dependent
      manner. After PMA treatment, the MME mRNA level was maximal between 4 h and 9 h
      (medium-term response), and the mean amplitude of the response to a concentration
      of 100 nM was 2.5-fold (P<0.01). LPS did not induce any significant change in MME
      mRNA level even when 1% serum was added to the cultures. Following dexamethasone
      treatment, the MME mRNA level was minimal between 21 h and 33 h (long-term
      response), and the mean amplitude of the response to a concentration of 100 nM
      was 0.49-fold (P < 0.05). Using actinomycin D, it appeared that the inhibition of
      RNA synthesis reduces the ulterior stimulating effect of PMA from 184% to 121%,
      and that MME mRNA has a half-life longer than 8 h, which is not diminished by
      dexamethasone. These results strongly suggest that the two factors modify MME
      mRNA level by stimulating (PMA) or inhibiting (dexamethasone) the transcription
      of the gene, rather than by modifying the transcript stability. Analysis of the
      cell-conditioned media by elastin zymography showed the MME as a lysis band in
      the 22-kDa region, the intensity of which varied with the treatments. The MME
      secretion is stimulated by PMA, inhibited by dexamethasone and does not show any
      variation after LPS treatment.

PMID- 9266702
TI  - Differences in metabolism and isomerization of all-trans-retinoic acid and 9-cis
      retinoic acid between human endothelial cells and hepatocytes.
AB  - Retinoic acid stimulates the expression of tissue-type plasminogen activator (t
      PA) in vascular endothelial cells in vitro and enhances t-PA levels in plasma and
      tissues in vivo. Compared with the in vivo situation, high retinoic acid
      concentrations are required to induce optimally t-PA expression in vitro. These
      findings led us to study retinoic acid metabolism in cultured human endothelial
      cells. For comparison, these studies were also performed in the human hepatoma
      cell line, HepG2, and key experiments were repeated with human primary
      hepatocytes. Both hepatocyte cultures gave very similar results. Human
      endothelial cells were shown to possess an active retinoic acid metabolizing
      capacity, which is quantitatively comparable to that of hepatocytes, but
      different from that of hepatocytes in several qualitative aspects. Our results
      demonstrate that all-trans-retinoic acid is quickly metabolized by both
      endothelial cells and hepatocytes. All-trans-retinoic acid induces its own
      metabolism in endothelial cells but not in hepatocytes. 9-cis-Retinoic acid is
      degraded slowly by endothelial cells, whereas hepatocytes metabolize 9-cis
      retinoic acid very quickly. Furthermore, our data show that hepatocytes, but not
      endothelial cells, detectably isomerise all-trans-retinoic acid to 9-cis-retinoic
      acid and vice versa. In both endothelial cells and hepatocytes all-trans-retinoic
      acid metabolism was inhibitable by the cytochrome P-450 inhibitors liarozole (10
      microM) and ketoconazole (10 microM), albeit to different extents and with
      different specificities. In the presence of the most potent retinoic acid
      metabolism inhibitor in endothelial cells, liarozole, at least 10-fold lower all
      trans-retinoic acid concentrations were required than in the absence of the
      inhibitor to obtain the same induction of t-PA. In conclusion, our results
      clearly demonstrate that all-trans-retinoic acid and 9-cis retinoic acid are
      actively but differently metabolized and isomerised by human endothelial cells
      and hepatocytes. The rapid metabolism of retinoic acid explains the relatively
      high concentrations of retinoic acid required to induce t-PA in cultured
      endothelial cells.

PMID- 9266703
TI  - Disruption of three acid proteases in Aspergillus niger--effects on protease
      spectrum, intracellular proteolysis, and degradation of target proteins.
AB  - Three acid protease genes encoding two extracellular proteases (PEPA and PEPB)
      and one intracellular protease (PEPE) were disrupted in Aspergillus niger.
      Northern-blot analysis showed the absence of wild-type protease mRNAs in the
      disruptants while western-blot analysis proved the absence of the encoded
      proteases. Characterization of the residual proteolytic spectra in the
      disruptants indicated that the extracellular protease activity was reduced to 16%
      and 94% for the delta pepA and the delta pepB disruptants, repectively. In the
      delta pepE disruptant, the total intracellular proteolytic activity was reduced
      to 32%. Apart from the reduced intracellular pepstatin-inhibitable aspartyl
      protease activity, serine protease and serine carboxypeptidase activities were
      also significantly reduced in the delta pepE strain. This may indicate the
      presence of a cascade activation mechanism for several vacuolar proteases,
      triggered by the PEPE protein, similar to the situation in Saccharomyces
      cerevisiae. Disruption of a single protease gene had no effects on the
      transcription of other non-disrupted protease genes in A. niger. In supernatants
      of the disruptants, reduced degradation of a proteolytically very susceptible
      tester protein (PELB) was observed. By recombination, we also constructed delta
      pepA delta pepB, delta pepB delta pepE and delta pepA delta pepE double
      disruptants as well as a delta pepA delta pepB delta pepE triple disruptant,
      lacking all three acid protease activities. The in vitro residual PELB activity
      was the highest in the triple disruptant and the delta pepA delta pepB
      recombinant.

PMID- 9266704
TI  - Gloverin, an antibacterial protein from the immune hemolymph of Hyalophora pupae.
AB  - Gloverin is an inducible antibacterial insect protein isolated from pupae of the
      giant silk moth Hyalophora. It is a basic (pI 8.5) protein with a molecular mass
      of 13.8 kDa, containing a large number of glycine residues (18.5%) but no
      cysteine, and has an amino acid sequence that reveals no strong degree of
      identity with any known proteins. Gloverin inhibits the growth of Escherichia
      coli at a minimal concentration of 1-3 microM, i.e. less than 5% of the
      concentration of gloverin in the hemolymph of infected pupae. The prime effect of
      gloverin, following its interaction with lipopolysaccharide (LPS) in the
      bacterial envelope, is a specific inhibition of the synthesis of vital outer
      membrane proteins, leading to an increased permeability of the outer membrane.
      The activity of gloverin is not affected by heating (100 degrees C, 10 min) but
      is inhibited by Mg2+ and by free LPS. The gloverin molecule will undergo
      conformational transitions from a monomeric random coil to an alpha-helix upon
      transfer from an aqueous to a hydrophobic environment, a property likely to be of
      importance for its interaction with cell-bound LPS. The activity of gloverin is
      in many respects similar to that of attacin, another antibacterial protein,
      originally found in Hyalophora [for a review see Boman, H. G., Faye, I.,
      Gudmundsson, G. H., Lee, J.-Y. & Lindholm, D. A. (1991) Eur J. Biochem. 201, 23
      31].

PMID- 9266705
TI  - Incomplete processing of type II procollagen by a rat chondrosarcoma cell line.
AB  - The Swarm rat chondrosarcoma cell line, RCS-LTC, deposits an extracellular matrix
      that contains the typical type II, IX, and XI collagen phenotype of hyaline
      cartilage, but the fibrils appear abnormally thin. By N-terminal sequence
      analysis, the type II collagen from the matrix was shown to have retained its N
      propeptides with no evidence of normal processing to type II collagen.
      Amplification and sequencing of cDNA prepared from the pro alpha1(II) mRNA of
      these cells showed a normal N-propeptide cleavage site. Furthermore, the type II
      N-procollagen could be processed to type II collagen by incubation with culture
      medium from normal chondrocytes. The findings indicate that the RCS-LTC cell line
      fails to express an active type II procollagen N-proteinase and, therefore,
      offers a useful culture system in which to study the role of N-propeptide removal
      in fibrillogenesis.

PMID- 9266706
TI  - Expression of CYP3A in the human liver--evidence that the shift between CYP3A7
      and CYP3A4 occurs immediately after birth.
AB  - CYP3A isoforms are responsible for the biotransformation of a wide variety of
      exogenous chemicals and endogenous steroids in human tissues. Two members of the
      CYP3A subfamily display developmentally regulated expression in the liver; CYP3A7
      is expressed in the fetal liver, whereas CYP3A4 is the major cyrochrome P-450
      isoform present in the adult liver. To gain insight into the descriptive
      ontogenesis of CYP3A isoforms during the neonatal period, we have developed
      several approaches to explore a neonatal liver bank. Although CYP3A4 and CYP3A7
      are structurally closely related, they differ in their capacity to carry out
      monooxygenase reactions. We have cloned CYP3A4 and CYP3A7 and established stable
      transfectants in Ad293 cells to investigate their substrate specificities. The
      16alpha hydroxylation of dehydroepiandrosterone is catalyzed by both proteins,
      but CYP3A7 has a higher affinity and maximal velocity than CYP3A4. Conversely,
      the conversion of testosterone into its 6beta derivative is essentially supported
      by CYP3A4. We used these two probes to determine the ontogenic evolution at the
      protein level; CYP3A7 was very active in the fetal liver and its activity was
      maximal during the first week following birth before to progressively decline and
      reached a very low level in adult livers. Conversely, the activity of CYP3A4 was
      extremely weak in the fetus and began to raise after birth to reach 30-40% of the
      adult activity after one month. CYP3A4 RNA accumulation displays a similar
      pattern of evolution; when probed with an oligonucleotide, its concentration
      increased rapidly after birth to reach a plateau as soon as the first week of
      age. These data supports the assumption that CYP3A4 expression is
      transcriptionally activated during the first week after birth and is accompanied
      by a simultaneous decrease of CYP3A7 expression, in such a way that the overall
      CYP3A protein content and the level of pentoxyresorufin dealkylase catalyzed by
      the two proteins remain nearly constant.

PMID- 9266707
TI  - Alkene monooxygenase from Nocardia corallina B-276 is a member of the class of
      dinuclear iron proteins capable of stereospecific epoxygenation reactions.
AB  - Nocardia corallina B-276 possesses a constitutive multi-component alkene
      monooxygenase which catalyses the epoxidation of terminal and sub-terminal
      alkenes. The epoxygenase component of this system has been purified with an
      overall yield of 35%. The electron paramagnetic resonance spectrum of the
      oxidised protein has a weak signal at g = 4.3, which we ascribe to rhombic iron
      and a free radical signal at g(ave) = 2.01. Upon partial reduction with
      dithionite using methyl viologen as a mediator, a signal at g(ave) = 1.9
      appeared. Upon further reduction with excess dithionite a signal at g = 15
      appeared with the concomitant disappearance of the g(ave) = 1.9 signal. These
      results indicate that the epoxygenase contains a bridged dinuclear iron centre
      similar to that found in a variety of proteins involved in oxygen transport and
      activation as well as desaturation of fatty acids. Analysis of the products of
      the reaction indicates that AMO is capable of stereospecific epoxidation of
      alkenes producing the R-enantiomer in high yield, a reaction catalysed by very
      few oxygenase enzymes. Whole cells gave lower enantiomeric excess values for the
      epoxide and a stereospecific epoxidase enzyme has been proposed to account for
      this difference. Although alkene monooxygenase was not inhibited by ethyne, a
      potent inhibitor of soluble methane monooxygenase with which alkene monooxygenase
      shares many common features, it was weakly inhibited by propyne with an apparent
      Km value of 340 microM. The mechanistic implications of these physicochemical
      features of the enzyme are discussed.

PMID- 9266708
TI  - Regulatory phosphorylation of banana fruit phosphoenolpyruvate carboxylase by a
      copurifying phosphoenolpyruvate carboxylase-kinase.
AB  - Phosphoenolpyruvate (P-pyruvate) carboxylase from ripened banana fruit was
      purified to near homogeneity and a final specific activity of 20-23 U/mg protein;
      P-pyruvate carboxylase-kinase copurified with P-pyruvate carboxylase throughout
      the purification. Gel filtration FPLC indicated that the two proteins form a
      tightly associated 425-kDa complex. Both the 103-kDa and 100-kDa subunits of the
      P-pyruvate carboxylase alpha2beta2 hetetrotetramer were phosphorylated and
      subsequently dephosphorylated in vitro in a time-dependent manner when the final
      preparation was incubated with 0.1 mM [gamma-32P]ATP followed by rabbit muscle
      protein phosphatase type 2A1. Phosphoamino acid and phosphopeptide map analyses
      indicated that in vitro phosphorylation of both subunits likely occurs at an
      identical Ser residue. Maximal stoichiometry of 32P incorporation was 0.2 and 0.4
      mol/mol 103-kDa and 100-kDa subunit, respectively. The level of 32P incorporation
      was correlated with the enzyme's activation state when assayed under suboptimal
      assay conditions (pH 7.3, 75 microM P-pyruvate, 0.2 mM L-malate). The main
      kinetic effect of phosphorylation was to decrease the enzyme's Km(P-pyruvate), as
      well as its sensitivity to inhibition by L-malate and L-glutamate. Banana P
      pyruvate carboxylase-kinase: (a) also phosphorylated maize leaf P-pyruvate
      carboxylase, histone III-S, and dephosphorylated casein; (b) demonstrated Mg2+
      dependence and Ca2+ independence, (c) exhibited a broad pH activity optimum of pH
      8.0-8.5, and (d) was inhibited by L-malate and activated by Ba2+ and Co2+. Time
      course kinetic studies suggested that P-pyruvate carboxylase exists mainly in the
      dephosphorylated form in preclimacteric, climacteric and postclimacteric fruit,
      but that its kinase is expressed throughout ripening. In situ 32P-labeling
      indicated that, while both subunits of ripe banana P-pyruvate carboxylase are
      phosphorylated in vivo, it is primarily the 100-kDa subunit that is radiolabeled.
      The results suggest that similar to the enzyme from leaves, root nodules and
      seeds, a fruit P-pyruvate carboxylase may be subject to regulatory seryl
      phosphorylation by an endogenous P-pyruvate carboxylase-kinase.

PMID- 9266709
TI  - Kininogen-derived fluorogenic substrates for investigating the vasoactive
      properties of rat tissue kallikreins--identification of a T-kinin-releasing rat
      kallikrein.
AB  - Peptide substrates with intramolecularly quenched fluorescence that reproduce the
      rat kininogen sequences at both ends of the bradykinin moiety were synthesized
      and used to investigate the kinin-releasing properties of five rat tissue
      kallikreins (rK1, rK2, rK7, rK9, rK10). Substrates derived from rat H- and L
      kininogen were cleaved best by rK1, especially that including the N-terminal
      insertion site of bradykinin, Abz-TSVIRRPQ-EDDnp(Abz = O-aminobenzoyl, EDDnp =
      ethylenediamine 2,4-dinitrophenyl), which was cleaved at the R-R bond with a
      k(cat)/Km of 12400 mM(-1) s(-1). Replacement of the P2' residue Pro by Val in Abz
      TSVIRRPQ-EDDnp gave a far less specific substrate that was rapidly hydrolysed by
      all five rat kallikreins and human kallikrein hK1. Peptidyl-N-methyl
      coumarylamide substrates, which lack prime residues, also had low specificities.
      The importance of the P2' residue for rK1 specificity was further demonstrated
      using a human-kininogen-derived substrate that included the N-terminal insertion
      site of bradykinin (Abz-LMKRP-EDDnp). This was cleaved at the M-K bond by hK1
      (kallidin-releasing site), but at the K-R bond (bradykinin-releasing site) by
      rK1. Competition experiments with Abz-TSVIRRPQ-EDDnp, which is resistant to most
      kallikreins, and Abz-TSVIRRVQ-EDDnp, a general kallikrein substrate, demonstrated
      that the former competitively inhibited hydrolysis by rK9 and hK1, with Ki values
      similar to the Km values for the substrate. Thus Pro in P2' does not prevent the
      peptide binding to the enzyme active site, but impairs cleavage of the scissile
      bond. The T-kininogen-derived substrate with the T-kinin C-terminal sequence (Abz
      FRLVR-EDDnp) was cleaved by rK10 (k(cat)/Km = 2310 mM(-1) s(-1)) and less rapidly
      by rK1, rK7 and hK1, at the R-L bond, while that corresponding to the N-terminal
      (Abz-ALDMMISRP-EDDnp) of T-kinin was resistant to all five kallikreins used,
      suggesting that none has T-kininogenase activity. But this substrate was
      hydrolysed by a semipurified sample of submandibular gland extract. Another
      kallikrein, identified as kallikrein rK3, was isolated from this fraction and
      shown to hydrolyze Abz-ALDMMISRP-EDDnp; rK3 also specifically released T-kinin
      from purified T1/T2-kininogen after HPLC fractionation. Injection of purified rK3
      and of Abz-ALDMMISRP-EDDnp-cleaving fractions into the circulation of
      anesthesized rats caused transient falls in blood pressure, as did purified rK1
      but none of the other purified rat or human kallikreins. This effect occurred via
      activation of the kinin system since it was blocked by Hoe140, a kinin receptor
      antagonist.

PMID- 9266710
TI  - Ca2+ and its substitutes have two different binding sites and roles in soluble,
      quinoprotein (pyrroloquinoline-quinone-containing) glucose dehydrogenase.
AB  - To investigate the mode of binding and the role of Ca2+ in soluble,
      pyrroloquinoline-quinone (PQQ)-containing glucose dehydrogenase of the bacterium
      Acinetobacter calcoaceticus (sGDH), the following enzyme species were prepared
      and their interconversions studied: monomeric apoenzyme (M); monomer with one
      firmly bound Ca2+ ion (M*); dimer consisting of 2 M* (D); dimer consisting of 2 M
      and 2 PQQ (Holo-Y); dimer consisting of D with 2 PQQ (Holo-X); fully
      reconstituted enzyme consisting of Holo-X with two extra Ca2+ ions (Holo) or
      substitutes for Ca2+ (hybrid Holo-enzymes). D and Holo are very stable enzyme
      species regarding monomerization and inactivation by chelator, respectively, the
      bound Ca2+ being locked up in such a way that it is not accessible to chelator. D
      can be converted into M* by heat treatment and the tightly bound Ca2+ can be
      removed from M* with chelator, transforming it into M. Reassociation of M* to D
      occurs spontaneously at 20 degrees C; reassociation of M to D occurs by adding a
      stoichiometric amount of Ca2+. Synergistic effects were exerted by bound Ca2+ and
      PQQ, each increasing the affinity of the protein for the other component.
      Dimerization of M to D occurred with Ca2+, Cd2+, Mn2+, and Sr2+ (in decreasing
      order of effectiveness), but not with Mg2+, Ba2+, Co2+, Ni2+, Zn2+, or monovalent
      cations. Conversion of inactive Holo-X into active Holo, was achieved with Ca2+
      or metal ions effective in dimerization. Although it is likely that activation of
      Holo-X involves binding of metal ion to PQQ, the spectral and enzymatic activity
      differences between normal Holo- and hybrid Holo-enzymes are relatively small.
      Titration experiments revealed that the two Ca2+ ions required for activation of
      Holo-X are even more firmly bound than the two required for dimerization of M and
      anchoring of PQQ. Although the two binding sites related with the dual function
      of Ca2+ show similar metal ion specificity, they are not identical. The presence
      of two different sites in sGDH appears to be unique because in other PQQ
      containing dehydrogenases, the PQQ-containing subunit has only one site. Given
      the broad spectrum of bivalent metal ions effective in reconstituting
      quinoprotein dehydrogenase apoenzymes to active holoenzymes, but the limited
      spectrum for an individual enzyme, the specificity is not so much determined by
      PQQ but by the variable metal-ion-binding sites.

PMID- 9266711
TI  - Mutational studies on conserved histidine residues in the chlorophyll-binding
      protein CP43 of photosystem II.
AB  - Two chlorophyll-binding antenna proteins in the photosystem II core, CP43 and
      CP47, are structurally similar and are thought to have evolved from a common
      ancestor. Several conserved histidine residues in hydrophobic regions of CP47
      have been shown to be important for photosystem II structure, function, and
      energy transfer. The purpose of this study was to determine whether similarly
      located histidine residues in CP43 function in a similar way. Three conserved
      histidine residues in presumed membrane-spanning regions of CP43, His40, His105,
      and His119, were mutated to glutamine (Q) and tyrosine (Y). The strains H105Q,
      H119Q, and H119Y were photoautotrophs whereas H40Q, H40Y, and H105Y were obligate
      photoheterotrophs. The H40Y and H105Y strains lacked detectable amounts of
      photosystem II reaction centers and hence could not evolve oxygen whereas H40Q
      retained a significant amount of photosystem II and oxygen evolution capacity.
      The observation that mutation of histidine residues to tyrosine has more drastic
      effects than mutation of these residues to glutamine is in agreement with results
      obtained for CP47 and suggests the involvement of these residues in chlorophyll
      binding. The drastic functional changes observed upon mutating His40 and His105
      of CP43 are similar to those observed when mutating the corresponding histidine
      residues in CP47, thus suggesting that the similarity between CP43 and CP47
      extends to the relative importance of functionally relevant residues.
      Interestingly, the His40-->Gln mutation in CP43 had significant effects on
      photosystem II electron transfer in that it affected the thermodynamics of Q(A)-
      oxidation by Q(B) and increased the charge recombination rate between Q(A)- and
      donor side components. This indicates that relatively minor changes in CP43 can
      significantly impact the properties of the photosystem II reaction center. The
      implications of this finding are discussed.

PMID- 9266712
TI  - Isolation and properties of an ATP transporter from a strain of Aspergillus
      niger.
AB  - A purified ATP transporter from Aspergillus niger did not show release or uptake
      for any of the nucleotides (ADP or UTP) except ATP. The release and uptake did
      not result from non-specific binding, but appeared to be concentration-dependent
      processes. ATP was shown by a double-isotopic technique to be transported across
      membrane vesicles without degradation. The ATP-transport protein was purified to
      near homogeneity from the membrane vesicles of a strain of A. niger and its
      apparent Mr was approximately 60000. The purified protein showed the properties
      of a membrane-bound protein in that the carrier protein was shown, during the
      liposome-preparative process, to translocate from the aqueous phase into the
      lipid bilayer of the liposome, unlike the cytosolic protein glucose-6-phosphate
      dehydrogenase, which remained confined to the aqueous compartment. Mycobacillin,
      a lipid-reactive antibiotic, was bound to the transport protein at a site other
      than the ATP-binding site, leading to its enhanced release or uptake, which was
      very feeble in absence of the antibiotic.

PMID- 9266713
TI  - Changes in the electronic structure around Ni in oxidized and reduced selenium
      containing hydrogenases from Methanococcus voltae.
AB  - The selenium-containing F420-reducing hydrogenase from Methanococcus voltae was
      anaerobically purified to a specific hydrogen-uptake activity of 350 U/mg protein
      as determined with the natural electron acceptor. The concentrated enzyme was
      used for EPR-spectroscopic investigations. As isolated, the enzyme showed an EPR
      spectrum with g(xyz) values of 2.21, 2.15 and 2.01. Illumination of such samples
      at low temperatures led to an EPR spectrum with g(xyz) values of 2.05, 2.11 and
      2.29. These spectra are typical for [NiFe]hydrogenases in the active state.
      Spectra of samples enriched in 77Se showed a hyperfine interaction between the
      unpaired spin of the nickel ion and the nuclear spin of one 77Se atom before and
      after illumination. A 90 degree flip of the electronic z-axis is proposed to
      explain the hyperfine interaction in both states. This has been demonstrated
      previously only for the F420-non-reducing hydrogenase from M. voltae, where the
      selenium atom is present as a selenocysteine residue on an unusually small
      separate subunit [Sorgenfrei, O., Klein, A. & Albracht, S. P. J. (1993) FEBS
      Lett. 332, 291-297]. The results demonstrate that the three-dimensional
      structures of the active sites in the selenium-containing F420-reducing and F420
      non-reducing hydrogenases from M. voltae are highly similar and hence are not
      influenced by the unusual subunit structure of the latter enzyme. Oxidized
      samples containing either natural selenium or 77Se were prepared from the F420
      reducing and the selenium-containing F420-non-reducing hydrogenase. Both enzymes
      exhibited EPR spectra typical for [NiFe]hydrogenases in the inactive 'ready'
      state. In contrast to the reduced form, no splitting of the nickel-derived signal
      due to the nuclear spin of 77Se was observed in the oxidized state, indicating
      that the electronic z-axis is perpendicular to the Ni-Se direction.

PMID- 9266714
TI  - The binding of azide to copper-containing and cobalt-containing forms of
      hemocyanin from the mediterranean crab Carcinus aestuarii.
AB  - To establish the competence of the active site of hemocyanin to acquire diverse
      coordination geometries, the binding of azide to three forms of a crab
      hemocyanin, the dinuclear cupric or met-hemocyanin, the mononuclear cupric or met
      apo-hemocyanin, and the mononuclear Co(II)-substituted derivative has been
      studied by near-ultraviolet circular dichroism and EPR spectroscopies. The near
      ultraviolet circular dichroism spectra of the various derivatives present
      qualitatively similar features, namely a negative peak around 335 nm in the case
      of the two copper-containing derivatives and a three-component pattern with the
      Co(II) derivative. Upon decreasing the pH from 7.0 to 5.5 a decrease of optical
      activity is observed with all protein samples. The characteristic CD features,
      attributable to N(imidazole)-to-metal and to OH -to-metal charge-transfer
      transitions, are strongly affected by azide binding. In particular, the intensity
      of the negative band exhibited by the two copper-containing protein forms
      decreases with the onset of a new negative feature with maximum around 400 nm
      diagnostic for azide-to-Cu(II) charge-transfer transitions. The visible region is
      affected as well, indicating that changes in the coordination sphere of copper
      take place. The affinity for azide of the different protein forms is higher at
      low pH. EPR measurements on the paramagnetic met-apo-hemocyanin derivative as a
      function of pH demonstrate heterogeneity in the coordination environment at low
      pH. In the presence of azide an increase of rhombic distortion of the EPR spectra
      is observed and on the basis of the identified sets of copper hyperfine features
      in the course of azide titration experiments two different azide bound forms of
      met-apo-hemocyanin can be detected. The CD and EPR data at the different pH
      values are consistent with a reaction scheme in which azide replaces a fourth
      ligand in the metal-coordination sphere, identified as a water or hydroxide
      molecule.

PMID- 9266715
TI  - Developmentally controlled cleavage of the Calliphora arylphorin receptor and
      posttranslational action of the steroid hormone 20-hydroxyecdysone.
AB  - In response to a rise in ecdysteroid titre, fat body cells of insect larvae take
      up storage proteins from the haemolymph by receptor-mediated endocytosis. Here we
      show that the receptor responsible for incorporation of the major haemolymph
      protein arylphorin of the blowfly, Calliphora vicina, is subject to an unusual
      posttranslational processing that involves three distinct cleavage steps. After
      the removal of a 17-amino-acid signal peptide, a receptor precursor of 141 kDa is
      released. Before reaching the cell surface, the precursor is cleaved a second
      time, giving rise to the active 92-kDa arylphorin receptor, plus a 48-kDa
      peptide. The function of this 48-kDa peptide may be the prevention of premature
      ligand-receptor interaction in the endoplasmic reticulum. 20-Hydroxyecdysone
      initiates a third cleavage step of the arylphorin receptor, which results in a 62
      kDa arylphorin binding protein and a 30-kDa peptide. Contrary to the standard
      model of steroid hormone action, the process which give rise to receptor cleavage
      can be induced by 20-hydroxyecdysone in vivo and in vitro even in absence of
      protein biosynthesis.

PMID- 9266716
TI  - Dimerization of Cdc25p, the guanine-nucleotide exchange factor for Ras from
      Saccharomyces cerevisiae, and its interaction with Sdc25p.
AB  - The oligomerization state of Cdc25p, the guanine nucleotide exchange factor for
      ras from yeast, was analyzed using different complementary approaches. The two
      hybrid system showed that the C-terminal part of Cdc25p (Cdc25-Ct) can interact
      with itself but also with Sdc25p-Ct, the corresponding part of Sdc25p, the other
      guanine exchange factor from yeast. The homotropic interaction of Cdc25p-Ct has
      been confirmed in yeast using immunoprecipitation experiments with epitope-tagged
      and beta-galactosidase-fused polypeptides. No other component was required for
      this interaction, since dimerization was shown to occur with material synthesized
      in vitro. The size of Cdc25-Ct produced in Escherichia coli has been directly
      measured on gel filtration columns and corresponds to a dimer. The dimerization
      domain is localized in the same part of the molecule as the catalytic domain and
      the portion responsible for membrane localization. The biological relevance of
      dimerization is still an open question, however by allowing heterodimerization
      with Sdc25p it could permit a more complex combinatorial regulation of ras in
      yeast.

PMID- 9266717
TI  - Structural determination of the O-linked sialyl oligosaccharides liberated from
      fetuin with endo-alpha-N-acetylgalactosaminidase-S by HPLC analysis and 600-MHz
      1H-NMR spectroscopy.
AB  - The endo-alpha-N-acetylgalactosaminidase from the culture medium of Streptomyces
      sp. OH-11242 (endo-GalNAc-ase-S) hydrolyzed the O-glycosidic linkage between
      GalNAc and Ser (Thr) in fetuin, liberating oligosaccharides. The O-linked
      oligosaccharides liberated from the fetuin with endo-GalNAc-ase-S were
      pyridylaminated following fractionation on a Bio-Gel P-4 column. The structure of
      the pyridylaminated O-linked oligosaccharides from fetuin has been determined by
      reverse-phase HPLC and 600-MHz 1H-NMR spectroscopy. The chemical shifts and the
      coupling constants of pyridylaminated (PA) NeuAc alpha2-3Gal beta1-3GalNAc were
      refined by computer simulation of the spectrum. The structures of NeuAc alpha2
      3Gal beta1-3(NeuAc alpha2-6)GalNAc-PA and NeuAc alpha2-3Gal beta1-3(NeuAc alpha2
      3Gal beta1-4GlcNAc beta1-6)GalNAc-PA were determined by their structural reporter
      groups.

PMID- 9266718
TI  - Deletion of the heptosyltransferase genes rfaC and rfaF in Escherichia coli K-12
      results in an Re-type lipopolysaccharide with a high degree of 2-aminoethanol
      phosphate substitution.
AB  - The chromosomal genes rfaC and rfaF of Escherichia coli W3110 were inactivated by
      allelic-replacement mutagenesis to generate a defined strain lacking both
      heptosyltransferases which catalyze in lipopolysaccharide (LPS) biosynthesis the
      transfer of the first two L-glycero-D-manno-heptose (Hep) residues to 3-deoxy-D
      manno-2-octulosonic acid (Kdo). The LPS of the mutant was isolated and its
      chemical structure was investigated by compositional analysis and nuclear
      magnetic resonance spectroscopy of isolated, deacylated oligosaccharide
      phosphates. The basic structure was a tetrasaccharide alpha-Kdo-(2-->4)-alpha-Kdo
      (2-->6)-beta-D-GlcN4P-(1-->6)-alpha-D- GlcN1P which in LPS was substituted at
      position 07 of Kdo II by 2-aminoethanol phosphate in non-stoichiometric amounts.
      2-Aminoethanol was cleaved during deacylation of the LPS by successive
      hydrazinolysis and KOH treatment and, in addition, phosphate migration from 07 to
      08 of Kdo II occurred. Thus, the oligosaccharides alpha-Kdo7P-(2-->4)-alpha-Kdo
      (2-->6)-beta-D-GlcN4P-(1-->6)- alpha-D-GlcN1P and alpha-Kdo8P-(2-->4)-alpha-Kdo
      (2-->6)-beta-D-GlcN4P-(1-->6)- alpha-D-GlcN1P could be isolated. KOH treatment of
      the two trisphosphates and authentic methyl 3-deoxy-D-manno-octulopyranoside 7-(2
      acetamidoethyl phosphate) proved that phosphate migration only took place when
      the phosphate group was substituted with 2-aminoethanol. Complementation studies
      with plasmid-encoded rfaC and rfaF genes revealed that the mutant strain can be
      used in combination with LPS-specific antibodies for the cloning and
      characterization of heptosytransferases which glycosylate Kdo residues of the
      inner core region of LPS.

PMID- 9266720
TI  - IUPAC-IUBMB Joint Commission on Biochemical Nomenclature (JCBN) and Nomenclature
      Committee of IUBMB (NC-IUBMB). Newsletter 1996.

PMID- 9266719
TI  - Isolation and characterization of a cDNA from the rat brain that encodes
      hemoprotein heme oxygenase-3.
AB  - Two isozymes of heme oxygenase (HO), HO-1 or HSP32 and the constitutive form HO
      2, have been characterized to date. We report the discovery of a third protein
      species and refer to it as HO-3. HO-3 is the product of a single transcript of
      approximately 2.4 kb and can encode a protein of approximately 33 kDa. The HO-3
      transcript is found in the spleen, liver, thymus, prostate, heart, kidney, brain
      and testis and is the product of a single-copy gene. The predicted amino acid
      structure of HO-3 differs from both HO-1 (HSP32) and HO-2 but is closely related
      to HO-2 (approximately 90%). Escherichia coli expressed and purified HO-3 protein
      does not cross react with polyclonal antibodies to either rat HO-1 or HO-2, is a
      poor heme catalyst, and displays hemoprotein spectral characteristics. The
      predicted protein has two heme regulatory motifs that may be involved in heme
      binding. These motifs and the hemoprotein nature of HO-3 suggest a potential
      regulatory role for the protein in cellular processes which are heme-dependent.

PMID- 9266721
TI  - Do posttranslational modifications of CuZnSOD lead to sporadic amyotrophic
      lateral sclerosis?

PMID- 9266722
TI  - Familial spongiform encephalopathy associated with a novel prion protein gene
      mutation.
AB  - Human prion diseases include Creutzfeldt-Jakob disease, Gerstmann-Straussler
      Scheinker disease, fatal familial insomnia, and kuru. Each of these diseases has
      a specific clinical presentation while spongiform encephalopathy, neuronal loss,
      and gliosis are their neuropathological hallmarks. We studied a Brazilian family
      with an autosomal dominant form of dementia. Nine members of the family were
      affected by a dementia with frontotemporal clinical features, with a mean age at
      onset of 44.8 +/- 3.8 years and a mean duration of symptoms of 4.2 +/- 2.4 years.
      Neuropathological examination of 3 patients showed severe spongiform change and
      neuronal loss in the deep cortical layers and in the putamen, but minimal gliosis
      in the most severely affected areas. The putamen and cerebellum, but not other
      areas of the affected brain, displayed prion protein immunoreactivity. A novel
      prion protein gene mutation causing a nonconservative substitution at codon 183
      was identified in 2 neuropathologically confirmed affected individuals (mother
      and son). The mutation was transmitted in a mendelian fashion to 12 members of
      the family. Therefore, we identified a novel prion disease variant characterized
      by an early onset and long duration of the symptoms, severe spongiform change
      with minimal gliosis, associated with a prion protein gene mutation at codon 183.

PMID- 9266723
TI  - Effect of Lambert-Eaton myasthenic syndrome antibodies on autonomic neurons in
      the mouse.
AB  - Somatic muscle weakness and autonomic symptoms characterize the autoimmune
      Lambert-Eaton myasthenic syndrome (LEMS). The former results from IgG
      autoantibody-mediated down-regulation of P/Q-type voltage-gated calcium channels
      at motor nerve terminals and consequent reduction in acetylcholine release; the
      basis for the autonomic symptoms is unknown. Using omega-conotoxins GVIA and
      MVIIC and omega-agatoxin IVA that block N-, Q-, and P-type channels, we
      investigated ex vivo the calcium channels subserving transmitter release from
      postganglionic parasympathetic neurons in the bladder and from postganglionic
      sympathetic neurons in the vas deferens of mice injected with IgG from LEMS
      patients or from controls. Calcium influx through N-, P-, and Q-type channels
      subserved transmitter release from parasympathetic and sympathetic neurons in
      control mice. In test mice, the component of transmitter release subserved by P
      type channels was abolished by four of four LEMS IgG preparations, that subserved
      by Q-type channels was significantly reduced by three, and that subserved by N
      type channels by one. Thus, LEMS IgG impairs transmitter release from
      parasympathetic and sympathetic neurons through down-regulation of one or more
      subtypes of voltage-gated calcium channels. The results suggest that antibody
      mediated interference with specific ion channel function may also underlie
      autonomic dysfunction occurring in other autoimmune diseases.

PMID- 9266724
TI  - Nicotinic receptor stimulation protects neurons against beta-amyloid toxicity.
AB  - beta-Amyloid (A beta), a major constituent of senile plaques in Alzheimer's
      disease (AD), is thought to contribute to the neurodegeneration. We examined the
      effects of nicotinic receptor agonists on A beta cytotoxicity in cultured rat
      cortical neurons. The number of viable neurons decreased significantly when
      cultures were exposed to synthetic A beta peptides (25-35). Concomitant
      administration of nicotine with A beta markedly reduced the number of dead cells.
      This nicotine-induced neuroprotection was dependent on the concentration. When
      hexamethonium or mecamylamine, nicotinic antagonist, was added, neuroprotective
      effect of nicotine was blocked, which indicates that effect of nicotine was
      mediated by nicotinic receptors. In addition, a selective alpha7-receptor
      antagonist, alpha-bungarotoxin (alpha-BTX), blocked the neuroprotective effect of
      nicotine. Furthermore, incubation with 3-(2,4)-dimethoxybenzylidene anabaseine
      (DMXB), a selective alpha7-receptor agonist, protected against A beta-induced
      neuronal death. These results suggest that alpha7-receptor activation plays an
      important role in neuroprotection against A beta cytotoxicity. This study
      suggests that nicotinic receptor stimulation, especially alpha7-receptor
      activation, may be able to protect neurons from degeneration induced by A beta
      and may have effects that counter the progress of AD.

PMID- 9266725
TI  - Ischemic lesion volumes in acute stroke by diffusion-weighted magnetic resonance
      imaging correlate with clinical outcome.
AB  - Diffusion-weighted magnetic resonance imaging detects ischemic injury within
      minutes after onset, and has been used to demonstrate drug efficacy in animal
      models of stroke. In 50 patients diagnosed with acute ischemic stroke (<24-hour
      duration) within the middle cerebral artery territory, lesion volume was measured
      by diffusion-weighted imaging. Thirty-four patients also had volumes measured by
      T2-weighted imaging chronically (median time, 7.5 weeks; mean, 15.9 weeks).
      Clinical severity was measured by the National Institutes of Health Stroke Scale
      Score and the Barthel index. Acute lesion volumes correlated with the acute
      stroke scale score (r = 0.56), the chronic stroke scale score (r = 0.63), and
      chronic lesion volumes (r = 0.84). Chronic volumes correlated with the chronic
      stroke scale score (r = 0.86) and the Barthel index (r = -0.60). When only
      cortically based lesions were considered, the correlations relating acute lesion
      volume measured by diffusion-weighted imaging (r = 0.61) and chronic lesion
      volume measured by T2-weighted imaging (r = 0.90) to the chronic stroke scale
      score were higher. These results provide evidence that lesion volumes determined
      by diffusion-weighted imaging acutely may be predictive of clinical severity and
      outcome, and may support a role for diffusion-weighted imaging in the assessment
      of acute stroke therapies in clinical trials.

PMID- 9266726
TI  - Quantitative assessment of cardiovascular autonomic function in Guillain-Barre
      syndrome.
AB  - To study the temporal course and the relationship between autonomic failure and
      motor weakness in Guillain-Barre syndrome (GBS), a total of 164 autonomic
      function tests were serially applied for up to 1 year in 13 consecutive patients.
      Results were compared with those obtained in 25 healthy volunteers and 13
      patients with other neurological diseases. Parasympathetic function tests
      comprised heart rate responses to Valsalva maneuver, deep breathing, and active
      change of posture, whereas sympathetic vasomotor function was assessed by blood
      pressure responses to handgrip and standing. At the height of the disease,
      subclinical autonomic involvement of both parasympathetic and sympathetic arms
      was revealed in the vast majority of patients. Abnormalities of autonomic
      function tests improved gradually over time, paralleling the recovery of motor
      function, but were only partially related to clinically significant autonomic
      dysfunction. Correlation analysis suggested that tachycardia in the context of
      GBS might be caused by a reduction of sympathetically mediated peripheral
      vascular tone rather than by vagal failure.

PMID- 9266727
TI  - Association of myopathy with large-scale mitochondrial DNA duplications and
      deletions: which is pathogenic?
AB  - We identified large-scale heteroplasmic mitochondrial DNA (mtDNA) rearrangements
      in a 50-year-old woman with an adult-onset progressive myopathy. The predominant
      mtDNA abnormality was a 21.2-kb duplicated molecule. In addition, a small
      population of the corresponding partially deleted 4.6-kb molecule was detected.
      Skeletal muscle histology revealed fibers that were negative for cytochrome c
      oxidase (COX) activity and had reduced mtDNA-encoded COX subunits. By single
      fiber polymerase chain reaction analysis, COX-negative fibers contained a low
      number of wild-type or duplicated mtDNA molecules (ie, nondeleted). In situ
      hybridization demonstrated that the abnormal fibers contained increased amounts
      of mtDNA compared with normal fibers and that most of the genomes were deleted.
      We concluded that deleted mtDNA molecules were primarily responsible for the
      phenotype in this patient.

PMID- 9266728
TI  - Otolith-ocular responses in familial episodic ataxia linked to chromosome 19p.
AB  - We evaluated several members of a family with episodic ataxia type 2 linked to
      chromosome 19p by using a battery of vestibulo-ocular reflex (VOR) tests. Testing
      focused on the otolith-ocular reflex and semicircular canal-otolith interaction.
      Our aims were to improve understanding of the structures important for the VOR
      and to define further the range of vestibulo-ocular, in particular otolith
      ocular, manifestations within a family with episodic ataxia. Ocular motor,
      semicircular canal-ocular, and semicircular canal-otolith interaction assessments
      suggested impairment of the vestibulo-cerebellum (ie, the flocculonodular lobe);
      the brainstem appeared to be relatively spared. Eye movements during constant
      velocity off-vertical axis rotation (OVAR), a pure otolith stimulus, indicated
      that the modulation component of the response was normal whereas the bias
      component was reduced or nearly absent. Based on these data, it appears that the
      cerebellum is not responsible for the generation of the modulation component of
      the response to OVAR. However, the bias component appears to depend on the caudal
      midline cerebellum.

PMID- 9266729
TI  - Hippocampal N-acetylaspartate in neocortical epilepsy and mesial temporal lobe
      epilepsy.
AB  - Previous magnetic resonance spectroscopy (MRS) studies have shown that N
      acetylaspartate (NAA) is reduced not only in the ipsilateral but also in the
      contralateral hippocampus of many patients with mesial temporal lobe epilepsy
      (mTLE). The reason for the contralateral damage is not clear. To test whether the
      hippocampus is also damaged if the focus is outside the hippocampus, we have
      measured patients with neocortical epilepsy (NE). Therefore, the goals of this
      study were to determine if hippocampal NAA is reduced in NE and if hippocampal
      NAA discriminates NE from mTLE. MRS imaging (MRSI) studies were performed on 10
      NE patients and compared with MRSI results in 23 unilateral mTLE patients and 16
      controls. The results show that, in contrast to mTLE, NAA was not reduced in the
      hippocampus of NE patients, neither ipsilateral nor contralateral to the seizure
      focus. These results suggest that repeated seizures do not cause secondary damage
      to the hippocampus. The absence of spectroscopic differences in NE may help to
      distinguish NE from mTLE.

PMID- 9266730
TI  - Calcium-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
      receptors: a molecular determinant of selective vulnerability in amyotrophic
      lateral sclerosis.
AB  - The cause of the selective degeneration of motor neurons in amyotrophic lateral
      sclerosis (ALS) remains unexplained. One potential pathogenetic mechanism is
      chronic toxicity due to disturbances of the glutamatergic neurotransmitter
      system, mediated via alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
      (AMPA)-sensitive glutamate receptors. Functional AMPA receptors consist of
      various combinations of four subunits (designated GluR1-4). The GluR2 subunit is
      functionally dominant and renders AMPA receptors impermeable to calcium. Most
      native AMPA receptors in the mammalian central nervous system (CNS) contain the
      GluR2 subunit and are calcium impermeable. We have investigated the composition
      of AMPA receptors expressed on normal human spinal motor neurons by in situ
      hybridization to determine their likely subunit stoichiometry. Highly significant
      levels of mRNA were detected for the GluR1, GluR3, and GluR4 subunits. However,
      GluR2 subunit mRNA was not detectable in this cell group. The absence of
      detectable GluR2 mRNA in normal human spinal motor neurons predicts that they
      express calcium-permeable AMPA receptors unlike most neuronal groups in the human
      CNS. Expression of atypical calcium-permeable AMPA receptors by human motor
      neurons provides a possible mechanism whereby disturbances of glutamate
      neurotransmission in ALS may selectively injure this cell group.

PMID- 9266731
TI  - Glial cell line-derived neurotrophic factor-levodopa interactions and reduction
      of side effects in parkinsonian monkeys.
AB  - Glial cell line-derived neurotrophic factor (GDNF) stimulates the nigrostriatal
      dopaminergic pathway and improves motor functions in animal models of
      parkinsonism. Sinemet is currently the most widely used drug for treating
      Parkinson's disease. The present study has evaluated GDNF-Sinemet interactions in
      parkinsonian rhesus monkeys. Both GDNF and Sinemet, when given alone,
      significantly improved total parkinsonian scores. The response to Sinemet did not
      change after intracerebroventricular vehicle injections. In contrast, there was a
      functional interaction between GDNF and levodopa. When comparing the levodopa
      dose response before and after GDNF treatment, significant behavioral
      improvements were seen after trophic factor administration at every levodopa dose
      level except 500 mg. Adverse responses to Sinemet treatment alone in parkinsonian
      animals included vomiting, dykinesias, dystonias, and stereotypic movements.
      Combined GDNF-Sinemet treatment significantly reduced the occurrence of these
      levodopa-induced side effects, with a >90% decrease in adverse responses seen at
      the mid-Sinemet (250 mg levodopa-25 mg carbidopa) dose level. The only side
      effect from GDNF treatment was a transitory weight loss. Thus, combined GDNF
      Sinemet treatment could be of therapeutic value in treating parkinsonism, by
      producing a greater functional response and by mitigating adverse responses to
      Sinemet treatment.

PMID- 9266732
TI  - Dopamine D1 and D2 receptor gene expression in the striatum in Huntington's
      disease.
AB  - The cellular expression of dopamine D1 and D2 receptor mRNAs was investigated in
      the postmortem human caudate nucleus of control cases and genetically and
      pathologically confirmed cases of Huntington's disease (HD) by using quantitative
      in situ hybridization. The HD cases were categorized (0-4) by severity of
      striatal neuropathology according to the Vonsattel scale. For the HD grade 0
      case, a pronounced reduction in the number of D1 and D2 mRNA-positive cells was
      observed compared with controls; however, the abundance of both receptor mRNAs
      per remaining cell was within the control range. For D2 receptor mRNA, the number
      of detectable D2-positive medium-sized cells decreased with increasing pathology;
      this decrease was accompanied by a gradual reduction in the intensity of D2
      signal per cell. By contrast, for D1 receptor mRNA, despite a decrease in the
      number of D1 mRNA-positive cells detected, the average cellular expression of D1
      mRNA was markedly reduced in the HD grade 1 case and then increased (relative to
      the grade 1 case) with increasing pathology, presumably reflecting the relative
      survival of D1-expressing striatal interneurons. The implications of these
      findings for providing further information on the neurodegenerative process in HD
      are discussed.

PMID- 9266733
TI  - A biochemical, genetic, and clinical survey of autosomal recessive limb girdle
      muscular dystrophies in Turkey.
AB  - Autosomal recessive limb girdle muscular dystrophy (LGMD2) is a clinically and
      genetically heterogenous group of diseases involving at least six different loci.
      Five genes have already been identified: calpain-3 at LGMD2A (15q15), and four
      members of the sarcoglycan (SG) complex, alpha-SG at LGMD2D (17q21), beta-SG at
      LGMD2E (4q12), gamma-SG at LGMD2C (13q12), and delta-SG at LGMD2F (5q33-q34). The
      gene product at LGMD2B (2p13-p16) is still unknown and at least one other gene is
      still unmapped. We investigated 20 Turkish families (18 consanguineous) diagnosed
      as having LGMD2. Most of our patients had onset of symptoms before age 10. The
      phenotypes varied from severe to benign. We analyzed the SG complex by
      immunofluorescence and/or western blot. Genotyping was performed using markers
      defining the six known loci and the suspected genes were screened for mutations.
      Six of 17 index cases showed deficiency of the SG complex, by immunofluorescence
      and/or western blot. Seven cases involved one of the known genes of the SG
      complex (alpha, 2; beta, 1; and gamma, 4 cases), and five mutations were
      documented in the alpha- and gamma-SG genes. After linkage analysis, 10 families
      were characterized as having LGMD2A (calpain-3 deficiency), and all mutations
      were eventually identified. One family was classified as having LGMD2B and 1
      family that has normal SGs was linked to the chromosome 5q33-q34 locus (LGMD2F).
      In 1 family there was no linkage to any of the known LGMD2 loci. It appears that
      in Turkey, there is a broad spectrum of genes and defects involved in LGMD2. It
      may be possible to correlate genotype to phenotype in LGMD2. All severe cases
      belonged to the gamma-SG-deficiency group. Nine calpain-3-deficient cases had
      intermediate and 1 had moderate clinical courses. The LGMD2B patient had a
      moderate clinical expression, whereas the LGMD2F case was truly benign.

PMID- 9266735
TI  - The impact of inpatient rehabilitation on progressive multiple sclerosis.
AB  - One of the primary aims of rehabilitation for patients with multiple sclerosis
      (MS) is to reduce their levels of disability and handicap, yet little systematic
      research into the outcomes of this intervention has been undertaken. This
      stratified, randomized, wait-list controlled study evaluated the effectiveness of
      a short period of multidisciplinary inpatient rehabilitation in people with MS.
      Sixty-six patients in the progressive phase of the disease were assessed at 0 and
      6 weeks with validated measures of impairment (Expanded Disability Status Scale
      and Functional Systems), disability (Functional Independence Measure), and
      handicap (London Handicap Scale). Both groups were comparable in terms of age,
      sex, disease duration and severity, disability, and handicap. At the end of 6
      weeks, although the level of impairment in both groups remained the same, those
      who participated in a short period of inpatient rehabilitation (average of 25
      days) significantly improved their level of disability and handicap compared with
      those in the wait-list control group. Despite unchanging impairment, inpatient
      rehabilitation resulted in reduced disability and handicap in patients with
      progressive MS.

PMID- 9266734
TI  - Reduced TSC2 RNA and protein in sporadic astrocytomas and ependymomas.
AB  - Individuals affected with tuberous sclerosis complex (TSC) develop several benign
      and malignant tumors at increased frequency, including astrocytomas. Tuberin, the
      protein product of the tuberous sclerosis complex-2 (TSC2) tumor suppressor gene,
      has been shown to directly inhibit cell growth and is expressed at high levels in
      normal central nervous system neurons and astrocytes. To determine whether TSC2
      RNA and protein are reduced in astrocytomas from individuals without tuberous
      sclerosis, reverse transcriptase-polymerase chain reaction and immunoblotting
      analyses were performed on 49 adult astrocytomas, 10 pediatric astrocytomas, and
      13 ependymomas. Eighteen of 40 (45%) high-grade (World Health Organization [WHO]
      grade III/IV) astrocytomas and 4 of 8 (50%) adult low-grade (WHO grade II)
      astrocytomas demonstrated reduced or absent TSC2 expression, including 1 giant
      cell astrocytoma, whereas none of the 10 pediatric low-grade astrocytomas
      analyzed showed a reduction in TSC2 expression. Reduced or absent tuberin was
      observed in 2 of 6 (33%) ependymomas analyzed. These data demonstrate, for the
      first time, that reduced or absent TSC2 expression may represent one of the
      critical genetic events associated with the development of sporadic adult, but
      not pediatric, astrocytomas.

PMID- 9266736
TI  - Long-duration response to levodopa influences the pharmacodynamics of short
      duration response in Parkinson's disease.
AB  - The long-duration response (LDR) to chronic levodopa treatment may mask the short
      duration response (SDR) to a single dose of the drug in Parkinson's disease (PD).
      As a result, the measurement of SDR may be inaccurate for establishing levodopa
      dosing regimen in individual patients. To evaluate the possible contamination of
      SDR by LDR, we investigated in 16 patients with PD the characteristics of SDR to
      a single dose of levodopa administered after a prolonged washout from chronic
      therapy and after a 15-day treatment period with levodopa. Levodopa treatment
      produced a sustained LDR, and the SDR, measured on the 15th day of treatment, had
      lower magnitude and shorter duration than the response recorded after washout.
      Moreover, after treatment, SDR did not vary between patients with mild and severe
      PD, whereas, after washout, severely affected patients had larger but shorter SDR
      than mildly affected patients. The evaluation of SDR without the interference of
      LDR is critical in defining the characteristics of the therapeutic response to
      levodopa.

PMID- 9266737
TI  - X-linked Emery-Dreifuss muscular dystrophy can be diagnosed from skin biopsy or
      blood sample.
AB  - We have raised an anti-emerin polyclonal antibody against a fusion protein
      encompassing most of the hydrophilic portion of emerin. Using this antibody, we
      have analyzed emerin expression in Emery-Dreifuss muscular dystrophy (EDMD)
      patients and controls, by immunocytochemistry, in skeletal muscle and skin, and
      by immunoblot, in peripheral blood mononuclear cells and lymphoblasts. Emerin was
      localized on the surfaces of nuclei in control skeletal muscle and skin but was
      absent or reduced in patient skeletal muscle, was absent from the skin of
      patients, and was expressed only in a few nuclei in a patient's mother.
      Immunoblot of peripheral blood cells from EDMD patients showed absence of the
      emerin band, altered-size emerin, or a protein of normal molecular mass but
      slightly reduced quantity. The diagnosis of X-linked EDMD is normally confirmed
      by genetic analysis of the STA gene coding for emerin. We propose
      immunocytochemical evaluation of emerin expression in skin biopsies as a
      sensitive and more convenient tool for diagnosing X-linked EDMD and, in
      particular, for distinguishing it from the autosomal dominant form. This
      technique may be applied to suspected EDMD patients, especially sporadic cases or
      those with incomplete clinical phenotype, and also suspected carriers. Immunoblot
      of peripheral blood cells is also useful, but it may not unequivocally identify
      carriers and some patients.

PMID- 9266738
TI  - A proposed mutation, Val781Ile, associated with hyperkalemic periodic paralysis
      and cardiac dysrhythmia is a benign polymorphism.
AB  - Twenty different point mutations have been identified in the gene coding for the
      alpha subunit of the adult skeletal muscle sodium channel in families with
      hyperkalemic periodic paralysis, paramyotonia congenita, and the potassium
      aggravated myotonias. One novel mutation (Val(781)Ile) was reported in an adopted
      boy with potassium-sensitive weakness and cardiac dysrhythmia. The confidence in
      establishing this rare amino acid substitution as a causative mutation was
      limited by the absence of family members for segregation analysis. Functional
      expression studies herein show that Val(781)Ile is most likely a benign
      polymorphism and not a disease-associated mutation.

PMID- 9266739
TI  - Maternally inherited encephalopathy associated with a single-base insertion in
      the mitochondrial tRNATrp gene.
AB  - We identified a single thymidine insertion at nucleotide position 5537 (T5537i)
      in the mitochondrial DNA transfer RNA gene for tryptophan in a family in which
      the proband had a progressive neurological disorder and his brother died in
      infancy of Leigh syndrome. Muscle biopsy from the proband showed subsarcolemmal
      proliferation of mitochondria and decreased activities of oxidative metabolism
      enzymes, in particular complex IV. Complex IV was also severely reduced in
      autopsy tissues, including heart and brain tissues, from the Leigh syndrome
      infant. The novel T5537i mutation was very abundant in tissues from the proband
      and the infant (>92%) and less abundant (range, 42-89%) in blood, hair follicles,
      and skin fibroblasts from 4 maternal relatives, 3 of whom showed a
      neuropsychiatric disturbance. The mutation was not found in more than 100 control
      subjects. The degree of heteroplasmy in blood correlated well with the severity
      of the clinical presentation, suggesting specific segregation with the disease.

PMID- 9266740
TI  - Coenzyme Q10 levels correlate with the activities of complexes I and II/III in
      mitochondria from parkinsonian and nonparkinsonian subjects.
AB  - The activities of complex I and complex II/III in platelet mitochondria are
      reduced in patients with early, untreated Parkinson's disease. Coenzyme Q10 is
      the electron acceptor for complex I and complex II. We found that the level of
      coenzyme Q10 was significantly lower in mitochondria from parkinsonian patients
      than in mitochondria from age- and sex-matched control subjects and that the
      levels of coenzyme Q10 and the activities of complex I and complex II/III were
      significantly correlated.

PMID- 9266741
TI  - Frataxin gene of Friedreich's ataxia is targeted to mitochondria.
AB  - Friedreich's ataxia is caused by a triplet repeat expansion in intron 1, a
      noncoding region of the frataxin gene (X25). We have generated a chimeric gene
      composed of the frataxin gene fused with the green fluorescent protein (GFP) gene
      as a reporter. Transfection of the fusion construct into living COS cells
      revealed that the frataxin-GFP construct localizes to organelles that double
      label with 8-(4'-chloromethyl) phenyl-2,3,5,6,11,12,14,15-octahydro-1H,4H,10H-13H
      diquinolizin o-8H-xanthylium chloride (CMXRos), a novel mitochondrial dye. Thus,
      frataxin appears to be a nuclear-encoded mitochondrial protein.

PMID- 9266742
TI  - Could a herpesvirus mimic tacrolimus-induced leukoencephalopathy?

PMID- 9266743
TI  - Tuberin loss from cerebral tissues.

PMID- 9266744
TI  - Bilateral parasagittal parietooccipital polymicrogyria and epilepsy.

PMID- 9266745
TI  - CuZnSOD-associated amyotrophic lateral sclerosis.

PMID- 9266746
TI  - Laser scanning confocal microscopy and factor analysis of biomedical image
      sequences (FAMIS) to detect and characterise HPV DNA sequences by FISH in HeLa
      cells.
AB  - Visualisation and localisation of specific DNA sequences were performed by
      fluorescence in situ hybridisation (FISH), confocal laser scanning microscopy
      (CLSM), and factor analysis of biomedical image sequences (FAMIS). HeLa cells
      containing 10-50 copies per cell of human papillomavirus (HPV) DNA type 18
      integrated in cellular DNA were used as a model. HPV-DNA was identified by DNA
      probes and DNA-DNA hybrids were revealed by alkaline phosphatase and Fast Red
      (FR) TR salt/naphtol-MX phosphate. Cell nuclei were counterstained with thiazole
      orange (TO). FAMIS summarises image sequences into a reduced number of images
      called factor images and curves called factors. Factor images correspond to
      spatial distributions of the different factors. Factors estimate different
      individual physical behaviours in the sequence (extinction velocity, spectral
      emission, depth emission profiles). We verified that HPV-DNA hybridisation
      signals are specific to the spectrum of FR, and distinguished between FR and TO.
      The latter result was found by taking into account differences in their
      extinction velocities. The focus of CLSM was improved on 3D image sequences, and
      the location of fluorescent signals inside the preparations was determined.
      Factor images showed that FR stained targets were located on different focal
      planes at the periphery of the nuclei.

PMID- 9266747
TI  - Assessment of cell proliferation by AgNOR scores and Ki-67 labeling indices and a
      comparison with potential doubling times.
AB  - The potential doubling time (T[pot]) has been proposed as a pretreatment
      estimator of intratreatment tumor proliferative capacity. The assay has several
      limitations, however, including the inability to discriminate between host and
      tumor cells in diploid tumors and the need for prospective labeling of patients
      with a halogenated pyrimidine. Often a separate biopsy is needed as well. In this
      study, Ki-67 immunostaining and AgNOR silver staining were examined as possible
      alternative methods by comparing them with the T[pot] in an in vitro system using
      two different cell lines under varying growth conditions. Using CaSki cells,
      nutritional status was varied to alter proliferation rates, and a strong
      correlation was found between Ki-67 labeling index and AgNOR scores (r = 0.927, P
      = 0.0003). Both Ki-67 labeling index and AgNOR scores had statistically
      significant inverse correlations with cell doubling time (T[d]), length of S
      phase (T[s]), and T(pot), as well as a positive correlation with iododeoxyuridine
      (IdUrd) labeling index. As an alternative method of inhibiting proliferation, 4
      hydroxytamoxifen (4OH-TAM), the potent anti-estrogenic metabolite of tamoxifen,
      was used to inhibit the proliferation of estrogen-dependent MCF-7 cells.
      Treatment with the anti-estrogen resulted in decreased Ki-67 labeling index and
      AgNOR scores of MCF-7 cells, correlating with a decrease in IdUrd labeling index
      and inversely correlating with T(pot). The significant correlations among Ki-67
      labeling index, AgNOR scores, and these other measures of proliferation suggest
      their potential value as indicators of proliferative activity. Retrospective
      markers, such as Ki-67 labeling index or AgNOR score, may be particularly
      attractive clinically in that prospective labeling of patients with halogenated
      pyrimidines could be avoided; however, extensive clinical testing will be
      required before the clinical usefulness of these markers can be established.

PMID- 9266748
TI  - Applying watershed algorithms to the segmentation of clustered nuclei.
AB  - Cluster division is a critical issue in fluorescence microscopy-based analytical
      cytology when preparation protocols do not provide appropriate separation of
      objects. Overlooking clustered nuclei and analyzing only isolated nuclei may
      dramatically increase analysis time or affect the statistical validation of the
      results. Automatic segmentation of clustered nuclei requires the implementation
      of specific image segmentation tools. Most algorithms are inspired by one of the
      two following strategies: 1) cluster division by the detection of internuclei
      gradients; or 2) division by definition of domains of influence (geometrical
      approach). Both strategies lead to completely different implementations, and
      usually algorithms based on a single view strategy fail to correctly segment most
      clustered nuclei, or perform well just for a specific type of sample. An
      algorithm based on morphological watersheds has been implemented and tested on
      the segmentation of microscopic nuclei clusters. This algorithm provides a tool
      that can be used for the implementation of both gradient- and domain-based
      algorithms, and, more importantly, for the implementation of mixed (gradient- and
      shape-based) algorithms. Using this algorithm, almost 90% of the test clusters
      were correctly segmented in peripheral blood and bone marrow preparations. The
      algorithm was valid for both types of samples, using the appropriate markers and
      transformations.

PMID- 9266749
TI  - Quantitation of cell-matrix adhesion using confocal image analysis of focal
      contact associated proteins and interference reflection microscopy.
AB  - We have developed an approach for the quantitation of vinculin, a focal contact
      associated protein, based on a multimodal confocal microscopy and image analysis.
      Vinculin spot distribution was imaged in confocal fluorescence microscopy and the
      corresponding focal contacts were imaged in confocal interference reflection
      microscopy. These images were analyzed with a SAMBA image cytometer. The image
      analysis program provided 12 morphometric features describing cellular area,
      shape, and proportions of vinculin spots as well as six topographical features
      describing the distribution of vinculin and the relative overlap of vinculin and
      focal contacts. This approach was applied to the study of rat osteosarcoma cells
      submitted to mechanical stresses: successions of 2g and 0g accelerations during a
      series of parabolic flights. The measured features were assessed by means of
      correlation analysis and stepwise discriminant analysis. After correlation
      analysis, only ten parameters were retained. Quantitation of cell morphological
      parameters indicated that cell area was significantly affected by gravitational
      stresses as well as vinculin distribution. Cell area was reduced by 50% and
      vinculin spots were restricted to cell periphery. Cell adhesion measured by IRM
      decreased significantly in the first part of the flight and remained stable at
      the end of the flight. These results suggest that cell-matrix adhesion is
      affected by gravitational stresses. Image analysis provides useful tools to
      investigate focal adhesion re-organization under different physiological stimuli.

PMID- 9266750
TI  - Automatic analysis of growth onset, growth rate and colony size of individual
      bone marrow progenitors.
AB  - A method for automatic enumeration of proliferating bone marrow progenitors after
      single cell sorting is described. The system is based on regular inverse
      microscopy, recording with a video camera, and image analysis using dedicated
      software on an Apple computer. Single CD34+ progenitor cells were sorted in 96
      well plates. Three times weekly phase-contrast video images of each well were
      stored and analyzed for the actual number of cells. From the subsequent counts
      growth curves were plotted for each individual progenitor. Enumeration by image
      analysis correlated very well with manual cell counting (r = 0.99, P < 0.0001).
      To show the capability of the method to analyze growth rate and growth delay,
      more differentiated (CD34+/CD13+/CD33+) progenitors were compared with more
      primitive (CD34+/CD13+/CD33g-) progenitors. Differences in the timing of colony
      outgrowth were shown to be based on delay in growth initiation. Initiation of
      growth was delayed 2.6-3.1 days in CD34+/CD13+/ CD33- fraction of 3 different
      donors (P < 0.0001). The growth rates of the progenitors in both fractions were
      not significantly different. The described method seems important to more
      accurately evaluate subpopulations of progenitors, the effect of growth promoting
      or inhibiting factors, and effects of cytotoxic drugs and irradiation.

PMID- 9266751
TI  - Fluorescent brighteners: novel stains for the flow cytometric analysis of
      microorganisms.
AB  - Flow cytometry is a rapid method for measuring the optical properties of
      individual cells. The technique has found great utility in the study of mammalian
      cells, but microbiological applications have been more limited. We here show that
      UV-excited fluorescent whitening agents, in particular Tinopal CBS-X, are
      effective stains for both vegetative microbial cells and for spores of Gram
      positive bacteria. Pretreatment of samples with ethanol speeds the staining
      process. Under favourable conditions, Tinopal CBS-X may be used to discriminate
      among organisms, a fact that may be useful when screening for a target
      microorganism against a high biological background.

PMID- 9266752
TI  - A flow cytometric method for measurement of intracellular chloride concentration
      in lymphocytes using the halide-specific probe 6-methoxy-N-(3-sulfopropyl)
      quinolinium (SPQ).
AB  - A flow cytometry method using the halide-specific fluorescent dye, 6-methoxy-N-(3
      sulfopropyl) quinolinium (SPQ), has been developed to measure intracellular
      chloride concentration in single cells. Collisions with chloride quench the
      fluorescence of SPQ, making it possible to relate the measured fluorescence
      intensity to chloride concentration with a Stern-Volmer equation. To demonstrate
      the method, porcine lymphocytes were loaded in vitro, using a hypotonic method,
      with 5 mM SPQ. Fluorescence excitation was provided by a UV laser and the
      fluorescence emission intensity at 485 nm was recorded. Calibration was performed
      by using 7 microM nigericin (a K/H antiporter) and 10 microM tributyltin (a Cl/OH
      antiporter) to equilibrate the concentrations of intracellular and extracellular
      chloride. Calibration measurements were made for chloride concentrations between
      0 mM and 140 mM. The calibration produced a Stern-Volmer quenching constant of
      16.2 M(-1) which was used to relate measured cell fluorescence to intracellular
      chloride concentration. The intracellular chloride concentration for fresh
      porcine lymphocytes was determined to be 56.2 +/- 3.3 mM. Stable loading of cells
      with 5 mM SPQ was accomplished in 15 minutes, leakage of SPQ from the cells was
      minimal, and over 95% of the cells remained viable after loading.

PMID- 9266753
TI  - A comparison of cytogenetic studies and flow cytometry in breast carcinomas.
AB  - In this study, we compared genetic instability in 70 breast carcinomas analyzed
      by two different methods, cytogenetics and flow cytometry. This comparison showed
      that each method has its strengths and weaknesses. Flow cytometry detected
      aneuploidy in 60% of cases, but missed most of the cytogenetically near-diploid
      clones and clones with simple chromosomal changes. Cytogenetics revealed
      chromosomal abnormalities in 50% of the samples. Simple chromosomal changes and
      multiploidy were readily detected by this method, but some of the clones with a
      high DNA index by flow cytometry were missed. The two methods gave corresponding
      results in the majority of cases (54%). In 17 cases, both methods detected
      matching abnormal clones (r = 0.93) but the DNA index was higher than predicted
      by the chromosome numbers. Most of the discrepancies might be explained by tumor
      heterogeneity and insufficient numbers of cells available for cytogenetic
      analyses. In seven cases, single-cell abnormalities were found that corresponded
      to a flow cytometry peak. Multiclonality was present in 25% of aneuploid tumors.
      No association was found between metaphases in cytogenetic preparations and
      increased S-phase fraction of the tumors, but aneuploid tumors had a
      significantly higher proliferation rate. Pooling data from both methods
      demonstrated that the majority of our samples were aneuploid (74%).

PMID- 9266754
TI  - Improved single laser measurement of two cellular antigens and DNA-ploidy by the
      combined use of propidium iodide and TO-PRO-3 iodide.
AB  - Recently, Frey (Cytometry 17:310-318, 1994) demonstrated that TO-PRO-3 iodide
      (TP3) can be excited indirectly by a 488 nm laser line through energy transfer by
      propidium iodide (PI). In the present study, we investigated whether PI-TP3
      energy transfer can help to overcome spectral cross talk problems associated with
      the combined use of fluorescein isothiocyanate (FITC), R-phycoerythrin (PE), and
      PI. Mixtures of keratin 8/18 FITC-labeled, keratin 8/18-PE-labeled, and unlabeled
      MCF-7 breast carcinoma cells were prepared and stained for DNA with PI (100
      microM). The effect of adding a range of TP3 concentrations (0.001 to 16 microM)
      to these mixtures was evaluated. The combined use of PI and TP3 was further
      evaluated using mixtures of unlabeled and p53 FITC-labeled COV362.cl4 ovarian
      cancer cells and mixtures of unlabeled and p53 FITC-labeled COV362.cl4 cells and
      peripheral blood lymphocytes (PBL), additionally stained for keratin 8/18 (PE).
      Finally, a human ovarian ascites tumor specimen was triple-stained for keratin
      8/18 (PE), vimentin (FITC) and DNA or keratin 8/18 (PE), PCNA (FITC) and DNA.
      Addition of TP3 allowed complete correction for spectral cross talk of PE/PI into
      the green fluorescence detector (FL1). Only minimal (FL1 - %FL2) compensation was
      required at a TP3 concentration of 2.0 microM in the presence of PI (100 microM).
      The PI spectral cross talk into the orange fluorescence detector (FL2) was
      reduced by about 50% using the same photomultiplier (PMT) settings. Although
      addition of TP3 reduced the signal-to-background ratio by about 30%, the
      advantage gained through full compensation for spectral cross talk resulted in an
      improved discrimination of p53-positive and -negative subpopulations in a mixture
      of human PBL and COV362.cl4 cells. Furthermore, vimentin-negative and PCNA
      negative cells were better resolved in a human DNA-aneuploid ovarian ascites
      tumor after staining the DNA with PI/TP3, rather than with PI alone. We conclude
      that the addition of TP3 to PI improves the combined measurement by single-laser
      flow cytometry of DNA-ploidy and antigen expression in heterogenous clinical
      samples.

PMID- 9266755
TI  - Structural analysis of the mouse prosaposin (SGP-1) gene reveals the presence of
      an exon that is alternatively spliced in transcribed mRNAs.
AB  - SGP-1/prosaposin can be secreted or targeted to the lysosomes where it is
      processed into smaller saposins A, B, C, and D required for the hydrolysis of
      glycosphingolipids. The deficiency of saposins B and C results in variant forms
      of metachromatic leukodystrophy and Gaucher's disease, respectively, which are
      characterized by lysosomal storage of undegraded glycosphingolipids. A required
      step to correct these genetic defects, or to understand the targeting mechanism
      of SGP-1 to the lysosomes, or to the extracellular space as well as its
      interaction with specific glycosphingolipids, is the analysis of the gene
      encoding this protein. Thus our investigation dealt with the molecular cloning of
      the mouse SGP-1 gene. Sequence analysis revealed that the mouse SGP-1 gene
      consists of 15 exons ranging from nine base pairs to 298 base pairs and 14
      introns, which ranged from 89 base pairs to >8 kb in length. Our data show that
      saposin A is encoded by the exons 3, 4, and 5, saposin B by exons 6, 7, 8, and 9,
      saposin C by exons 10 and 11, and saposin D by exons 12, 13, and 14. The
      translation start codon is located within exon 1, and the translation stop codon
      is located within exon 15. The exon/intron boundaries were in accordance to the
      AG/GT consensus sequences. Our data also revealed that the SGP-1 gene has an exon
      consisting of the nine base pairs (CAG GAT CAG) encoding the three amino acids of
      saposin B, which may be alternatively spliced in the SGP-1 mRNA. The presence of
      the different forms of alternatively spliced mRNAs in various tissues was
      analyzed by RT-PCR. This approach demonstrated that prosaposin mRNAs of brain,
      heart, and muscle contain the nine base pairs of exon 8, whereas the transcripts
      from testis, lung, pancreas, spleen, and kidney do not contain this exon 8.
      Sequence comparison between the human and mouse prosaposin showed that exon 11 of
      mouse SGP-1 consists of 279 base pairs, whereas the human prosaposin gene
      consists of 187 base pairs. The extra 93 base pairs encode 31 amino acids
      corresponding to a proline-rich region located between saposin C and saposin D in
      the mouse prosaposin molecule. Finally, the availability of these genomic clones
      provides a starting point for further studies on the genetic role of specific
      sequences on the structure and function of SGP-1/prosaposin and its derived
      saposin proteins. In conclusion, we cloned and sequenced the mouse prosaposin
      (SGP-1) gene. The structural analysis of this gene revealed the presence of an
      exon that is alternatively spliced in transcribed mRNAs in a tissue-specific
      manner.

PMID- 9266756
TI  - Morphological changes of in-vitro-produced bovine blastocysts after
      vitrification, in-straw direct rehydration, and culture.
AB  - Morphological signs of injury and regeneration following vitrification and
      warming of bovine embryos were studied by light and electron microscopy. In-vitro
      produced Day 7 expanded blastocysts (Day 0 = day of insemination) were vitrified
      by a two-step equilibration method using ethylene glycol and dimethyl sulphoxide
      as cryoprotectants. Thawing was performed by in-straw direct rehydration,
      followed by in vitro culture on a granulosa cell monolayer. Embryos were
      processed for transmission electron microscopy immediately after warming (0 hr)
      as well as after 4 hr or 24 hr of culture following warming. A control group of
      unfrozen embryos was also processed. At 0 hr after warming, except for a rapid
      collapse of the blastocoele, only minor changes were detectable by
      stereomicroscope. However, at the ultrastructural level, signs of extensive
      injury were seen, including a general distension or shrinkage of mitochondria,
      disintegration of cell adhesions between adjacent trophoblastic cells, and
      complete rupture of some cells. At 4 hr, stereomicroscopic investigation revealed
      collapsed blastocoele and a darkened granular appearance of the cell mass. At the
      ultrastructural level, signs of regeneration were also observable: cells with
      minor injuries were re-assembled in a central area forming a small blastocoele,
      cell adhesion structures were re-established, and damage of mitochondria was less
      severe. The majority of irreversibly damaged cells or cell debris was accumulated
      in the perivitelline space. At 24 hr, stereomicroscopic investigation of
      surviving blastocysts showed no signs of the previous injury. At the
      ultrastructural level, cellular debris in the perivitelline space and some
      degenerated cells in the blastocoele were the only signs of previous injuries. In
      conclusion, ultrastructural investigation revealed unexpectedly extensive damage
      followed by a rapid regeneration and reorganization of the embryonic structure.

PMID- 9266757
TI  - Developmental gene expression of procollagen III in bovine extraembryonic
      membranes during early pregnancy.
AB  - A major secretory protein produced by bovine chorioallantoic membranes, in vitro,
      was previously identified as the carboxyl-propeptide of alpha-1 type III
      collagen. In the present study, the protein and gene expression of procollagen
      III by bovine chorioallantois between days 17 and 45 of pregnancy was
      investigated. In addition, differential usage of multiple transcription
      termination sites by chorioallantois was examined. Two-dimensional PAGE of
      proteins synthesized and released by whole conceptuses or isolated
      chorioallantoic membranes into culture medium demonstrated that the C-terminal of
      procollagen III was not detectable before day 21 of pregnancy and concentrations
      increased thereafter. Developmental gene expression was determined by Northern
      blot analysis using a probe (A) that preceded all five polyadenylation sites of
      the previously sequenced clone 9.22. Procollagen III mRNA expression was
      undetectable at day 17, low on day 20, and increased through day 36. Two major
      transcripts of 5.9 and 4.9 kb were identified, the latter of which was expressed
      more prominently. A second probe (B), which terminated between poly-A sites 2 and
      3, was designed to identify transcripts that terminated at poly-A site 1 or 2.
      This probe bound to the 5.9-kb mRNA only. Two additional procollagen III cDNA
      clones were isolated from our bovine conceptus cDNA library and sequenced. One,
      designated 9.29, terminated at poly-A site 5. The other, designated 11.7,
      terminated at poly-A site 2, indicating that the bovine conceptus uses these stop
      sites in procollagen III transcription. Results from this study demonstrate that
      procollagen III gene and protein expression coincide with the development of the
      allantois, which progressively fuses with the chorion forming the chorioallantois
      placenta. In addition, multiple termination sites are used in procollagen III
      transcription.

PMID- 9266758
TI  - Ontogeny of temperature-regulated heat shock protein 70 synthesis in
      preimplantation bovine embryos.
AB  - Development of the preimplantation embryo is very susceptible to disruption by
      heat shock. As embryos proceed through development, they acquire resistance to
      heat shock, perhaps because they become transcriptionally active and can respond
      to environmental changes by undergoing transcriptionally-regulated cellular
      adaptation. Objectives were to determine the ontogeny of heat shock protein 70
      (HSP70) synthesis in preimplantation bovine embryos and to ascertain whether heat
      induced increases in HSP70 in embryos are caused by environmental alterations in
      gene expression. Exposure of bovine embryos to heat shock induced synthesis of a
      68 kDa form of HSP70 called HSP68 as early as the two-cell stage of development.
      Induction of HSP68 was alpha-amanitin independent at the two-cell stage but was
      blocked by alpha-amanitin as early as the early four-cell stage. Therefore, heat
      induced synthesis of HSP68 is regulated at the level of transcription at a time
      before the major round of embryonic genome activation is considered to occur. Two
      other constitutive HSP70 molecules were identified called heat shock cognates
      (HSC) 71 and 70; both proteins were synthesized during all stages of development
      from the two-cell to hatched blastocyst stages. However, heat-induced synthesis
      of HSC71 and HSC70 was not evident until the expanded blastocyst stage. In
      conclusion, environmental signals can activate gene expression before the major
      round of embryonic genome activation occurs in bovine embryos. Moreover,
      differences in thermal sensitivity of early embryos to heat shock is not caused
      by an inability to synthesize HSP70, suggesting that other mechanisms are
      involved in developmental acquisition of thermotolerance.

PMID- 9266759
TI  - Nucleolar substructures of rabbit cleaving embryos: an immunocytochemical study.
AB  - The structure-function relationships of the nucleolar substructures were studied
      in preimplantation rabbit embryos, where nucleologenesis is extending over the
      first four cell cycles and may not be synchronous in each blastomere.
      Immunocytochemical methods using light and electron microscopy were applied for
      protein and RNA localization as well as nick translation and terminal
      deoxynucleotidyl transferase techniques for DNA detection. DNA was gradually
      associated with the periphery of the compact nucleolar precursor bodies (NPBs)
      but was never found inside NPBs at the four-cell stage. In 16-cell embryos, some
      NPBs displayed a reticulated periphery forming the branching network of the dense
      fibrillar component (DFC) surrounding the "residual body" (remnant of NPB) in the
      process of activation. At the 32-cell stage, fully reticulated nucleoli were
      observed in each blastomere. DNA was then associated with the DFC of reticulated
      nucleoli. RNA was first detected at the 16 cell-stage in close contact with the
      DFC as well as inside the "residual body" which was not immunolabeled with the
      DNA antibodies used. When observed by light microscopy, fibrillarin, nucleolin,
      and protein B23 displayed a changing distribution pattern during nucleologenesis.
      At early stages (up to the 16-cell stage), small dot- and spot-like structures
      were distributed within the whole nuclei. In 16-cell embryos, these proteins
      started to accumulate in an irregular thin layer around the NPBs in the process
      of activation. The reorganization process described may be in relation with the
      redistribution of chromatin and nuclear/nucleolar matrix components during the
      activation of rDNA transcription localized in the NPB shell. In conclusion,
      nucleologenesis is only achieved at the fourth cell cycle in the cleaving rabbit
      embryo at the corresponding time when the first detectable nucleolus-associated
      RNA is detectable. Our results show a good correlation between the establishment
      of structure and function.

PMID- 9266760
TI  - Prolactin receptor expression in the developing mouse embryo.
AB  - We have examined the developmental pattern of prolactin receptor expression in
      the mouse by reverse transcription-polymerase chain reaction, in situ
      hybridization, and radioligand binding and have found two unexpected aspects of
      temporal regulation. First, high levels of prolactin receptor mRNA were detected
      in mouse embryos at day 8 and day 18, but levels decreased between these days to
      a minimum at approximately day 14. In contrast, placental prolactin receptor mRNA
      levels remained constant throughout this gestational period. Second, on embryonic
      day 16 the mRNA encoding the long form of the prolactin receptor is more abundant
      in the fetal liver than any of the short receptor form mRNAs, but by day 18 a
      switch occurs and the mRNA encoding one of the short receptor forms becomes the
      predominant receptor mRNA in that tissue. Expression of the receptor mRNA and
      protein is widespread throughout the fetus, with especially high levels in
      developing bone and cartilagenous structures, the thymus and pituitary, the
      tongue and skeletal muscle, and certain regions of the brain. The pattern of
      expression of prolactin receptor in the fetal mouse suggests an important role
      for the placental lactogens, the major ligands for fetal prolactin receptors, in
      fetal growth and development.

PMID- 9266761
TI  - Estrogen receptor protein and mRNA expression in the ovary of sheep.
AB  - Using immunohistochemistry and in situ hybridization, we attempted to identify
      the estrogen receptor (ER) protein and messenger RNA (mRNA) in sheep ovaries
      during the follicular phase of the estrous cycle. Monoclonal anti-ER antibodies
      H222 and 1D5 were used for localizing estrogen receptor on ovarian cryo-sections.
      Labeling for ER was found over the nuclei of surface epithelium, interstitial
      tissue, and granulosa cells of small as well as large ovarian follicles. In the
      preantral and small antral follicles, intense nuclear ER labeling was observed in
      mural granulosa cells and particularly in cumulus/granulosa cells surrounding the
      oocyte. In the large healthy looking follicles, greater diversity in labeling for
      ER was observed, which is characterized by mixed populations of granulosa cells
      expressing positive and more or less negative nuclear labeling. Such a pattern of
      labeling was particularly evident in follicles showing the signs of atresia.
      Generally, more intense nuclear staining was localized in granulosa cells
      proximal to basal membrane. In situ hybridization studies revealed the presence
      of ER mRNA in ovarian tissue. Autoradiographic visualization localized ER mRNA
      expression over the granulosa cells of healthy follicles of all sizes. Level of
      hybridization signal was comparable in mural and cumulus granulosa cells. In
      atretic follicles, the level of hybridization signal in granulosa cells was
      comparable to that of healthy follicles. A relatively weaker level of labeling
      was observed in granulosa cells dispersed in follicular antrum in follicles with
      advanced atretic lesions. Theca cells expressed a lower level of labeling than
      granulosa cells. Specificity of labeling for both ER protein and mRNA in ovary
      was proved by parallel probing the ovine uterus. Ovine ER recognition by both
      H222 and 1D5 antibodies was also proved by immunoblotting. These studies
      demonstrate the presence of the estrogen receptor and its messenger RNA in the
      sheep ovary and suggest an autocrine/paracrine role of estradiol and its receptor
      in the regulation of ovarian follicle development in sheep.

PMID- 9266762
TI  - Distribution of gelsolin in human testis.
AB  - Gelsolin, an actin-binding and severing protein present in many mammalian cells,
      was characterized in human testis. Although abundant in testicular extracts,
      gelsolin was not detected in purified spermatogenic cells by immunoblot analysis.
      Immunofluorescence studies of testis sections showed that gelsolin has two main
      localizations: peritubular cells and the seminiferous epithelium. In peritubular
      cells, gelsolin was present together with alpha-SM actin, in agreement with the
      myoid cell characteristics of these cells. In a large proportion of the tubules,
      gelsolin was found mainly, together with actin, in the apical part of the
      seminiferous epithelium. This localization of gelsolin also was observed in
      seminiferous tubules with a partial or complete absence of germinal cells, which
      evokes a presence of gelsolin at the apex of Sertoli cells. However, in normal
      testis, a complex pattern of gelsolin labeling was also present, mostly in the
      apical third of the epithelium, around cells or groups of cells, mainly
      spermatids, and, less frequently, in various other localizations from the apical
      to the basal part of the seminiferous epithelium. Taken together, these
      observations suggest that gelsolin may play different functions in the
      seminiferous epithelium: (1) regulation of the dynamic alterations of the actin
      cytoskeleton in the apical cytoplasm of Sertoli cells, and (2) modification of
      actin filaments assemblies in specific structures at germ cell-Sertoli cell
      contacts. Thereby, the actin-modulating properties of gelsolin are probably
      involved in reorganization of the seminiferous epithelium related to germ cell
      differentiation.

PMID- 9266763
TI  - Temporal expression and localization of protein farnesyltransferase during
      spermiogenesis and posttesticular sperm maturation in the hamster.
AB  - Spermiogenesis and posttesticular sperm maturation in the epididymis are distinct
      developmental processes that result in a polarized spermatozoon possessing a
      plasma membrane partitioned into segment-specific domains of distinct composition
      and function. The mechanisms that specify the distribution of intracellular
      organelles and target proteins to restricted membrane domains are not well
      understood. In this study we examined the expression pattern and distribution of
      protein farnesyltransferase (FTase) in hamster spermatids and epididymal
      spermatozoa to determine if protein lipidation may represent a potential
      mechanism to regulate protein association with specific organelles or the plasma
      membrane. Round spermatids exhibited only weak immunostaining with antibody
      against the beta-subunit of FTase, whereas elongating spermatids exhibited a high
      level of FTase expression that was segregated to the cytoplasmic lobe surrounding
      the anterior flagellum. Although FTase was released with the residual body,
      mature spermatids retained FTase within the midpiece and cytoplasmic droplet. In
      epididymal spermatozoa, FTase remained associated with the cytoplasmic droplet
      during its migration to the midpiece-principal piece junction; following release
      of the cytoplasmic droplet, no immunodetectable FTase was noted in the midpiece
      segment. Immunoblotting demonstrated the presence of both the alpha and beta
      subunits of FTase in sperm lysates. The temporal expression pattern and
      restricted distribution of FTase in spermatids and epididymal spermatozoa suggest
      a potential role in regulating protein association with specific organelles
      and/or membrane domains of the mature spermatozoon.

PMID- 9266765
TI  - Giant, accordioned sperm acrosomes of the greater bulldog bat, Noctilio
      leporinus.
AB  - Sperm of the greater bulldog bat Noctilio leporinus display an architecture that
      is totally unique among mammalian spermatozoa. The sperm head of Noctilio is
      extraordinarily large and flat and lies eccentrically with respect to the sperm
      tail. The major portion of the atypically large acrosome lies anterior to the
      nucleus and is shaped into a dozen accordionlike folds that run parallel to the
      long axis of the sperm. The ridge of each fold is shaped into approximately 60
      minute, evenly spaced rises that extend along the entire length of the fold. We
      speculate that acrosome ridges may serve to strengthen the sperm head during
      transport.

PMID- 9266764
TI  - A protein associated with the manchette during rat spermiogenesis is encoded by a
      gene of the TBP-1-like subfamily with highly conserved ATPase and protease
      domains.
AB  - We have used a rat pachytene spermatocyte cDNA expression library to clone TBP-1
      (for tat-binding protein-1; designated rat testis TBP-1 [rtTBP-1]), a new member
      of the family of putative ATPases associated with the 26S proteasome complex. The
      1.63 kb rtTBP-1 cDNA encodes a 49 kDa protein with 99% amino acid identity to
      human TBP-1 protein. rtTBP-1 protein contains a heptad repeat of six leucine-type
      zipper fingers at the amino terminal end and highly conserved ATPase and DNA/RNA
      helicase motifs towards the carboxyl terminal region. Chromatofocusing
      fractionation of rat testis sucrose extracts demonstrates that the encoded
      product, recognized by an antiserum raised to the first 196 amino acids of human
      TBP-1, consists of a protein triplet with a molecular mass range of 52-48 kDa and
      acidic pI (5.0-5.9). An identical immunoreactive triplet was detected by
      immunoblotting in extracts of fractionated pachytene spermatocytes, round
      spermatids and epididymal sperm. In situ hybridization using digoxigenin-labeled
      antisense RNA probes shows a predominant distribution of specific mRNA in the
      seminiferous epithelial region occupied by elongating spermatids and primary
      spermatocytes. Indirect immunofluorescence and immunogold electron microscopy
      studies show that rtTBP-1 immunoreactive sites colocalize with alpha-tubulin
      decorated manchettes of elongating spermatids. In addition, rtTBP-1
      immunoreactivity was detected in fibrillar and granular cytoplasmic bodies
      typically observed in spermatocytes and spermatids as well as in association with
      paraaxonemal mitochondria and outer dense fibers of the developing spermatid
      tail. Results of this study indicate that rtTBP-1 is a member of the highly
      evolutionary conserved TBP-1-like subfamily of putative ATPases, sharing regions
      of identity-including ATP-binding sites-with several subunits of the 26S
      proteasome, known to be involved in the ATP-dependent degradation of ubiquitin
      conjugated proteins.

PMID- 9266766
TI  - Diacylglycerol species as messengers and substrates for phosphatidylcholine re
      synthesis during Ca2+-dependent exocytosis in boar spermatozoa.
AB  - We have investigated pathways of lipid metabolism in spermatozoa and generation
      of various metabolites with potential messenger functions during exocytosis
      stimulated with A23187/Ca2+. Stimulation of boar spermatozoa resulted in a
      considerable rapid increase in saturated/unsaturated 1,2-diacylglycerol (1,2-SU
      DAG) and, concomitantly, a substantial reduction in disaturated 1,2
      diacylglycerol (1,2-DS-DAG), and in phosphatidylcholine (PC). These changes
      preceded the onset of exocytosis. Phosphatidic acid was sometimes generated in
      parallel, but usually rose later, suggesting that 1,2-SU-DAG may be formed
      directly by phospholipase C action. Lipid changes observed in stimulated
      spermatozoa that have been prelabelled with several lipid precursors
      ([14C]palmitic acid, [14C]glycerol, [14C]choline, or [14C]arachidonic acid)
      suggested the existence of a unique process involving the utilization of the high
      basal levels of 1,2-DS-DAG to form 1,2-SU-DAG, with the latter being subsequently
      employed to replenish the PC pool. An ensuing generation of lysoPC and
      arachidonic acid, which paralleled the occurrence of exocytosis, revealed that
      the newly synthesized PC was hydrolyzed by phospholipase A2. The highest levels
      of 1,2-SU-DAG, minimum levels of 1,2-DS-DAG, and the regeneration of the PC pool
      were tightly coupled to the beginning of visible exocytosis. These results
      suggest that changes in these lipid metabolites may be fundamental processes
      during acrosomal exocytosis occurring in response to physiological agonists.

PMID- 9266768
TI  - Changes in calpain during meiosis in the rat egg.
AB  - Resumption of meiosis at fertilization is mediated by increased levels of calcium
      which activate several calcium-dependent enzymes. Calpain, a neutral calcium
      activated thiol protease, is present in the cytoplasm of many cells. Its
      activation is associated with limited autolysis and relocalization in the cell.
      Calpain is thought to participate in the regulation of mitosis and resumption of
      meiosis in Xenopus oocytes. In this study we followed the activation and
      localization of calpain during maturation and fertilization in rat eggs using a
      polyclonal antibody raised against chicken muscle calpain. A band of 80 kDa was
      detected in GV oocytes and its level increased in unfertilized MII eggs. At the
      early stages of fertilization, we observed a transient decrease in the level of
      calpain which was regained at the pronuclear stage. Adding Ca2+ to lysate of MII
      eggs resulted in an additional band, representing the degraded fragment of the
      activated protein. In eggs activated by ionomycin, calpain level decreased,
      followed by an increase in a dynamic similar to that observed in fertilized eggs.
      Egg activation also led to changes in calpain localization. A homogenous
      distribution was observed in GV and in MII eggs, while in activated eggs it was
      localized predominantly overlying the metaphase plate. In the current study we
      demonstrate the presence of calpain in the rat egg. During maturation, calpain
      level increases; however, during egg activation, in response to [Ca2+]i changes,
      calpain undergoes autolysis, translocaton, and fluctuation in its level. We
      therefore suggest a correlation between calpain activation and fertilization.

PMID- 9266767
TI  - Members of the SNARE hypothesis are associated with cortical granule exocytosis
      in the sea urchin egg.
AB  - Cortical granule exocytosis is important for the block to polyspermy at
      fertilization in the eggs of most vertebrates and many invertebrates. Cortical
      granules are poised at the cell surface and exocytose in response to sperm
      stimulation. Following exocytosis, the cortical granule contents modify the
      extracellular environment of the egg, the major result of which is to block
      additional sperm binding. Here we show that proteins homologous to members of the
      SNARE hypothesis-a molecular model designed to explain the trafficking, docking,
      and exocytosis of vesicles in the secretory compartment-are present in eggs at
      the right time and place to be involved in the regulation of cortical granule
      exocytosis. Using polymerase chain reaction (PCR) screens we have found
      homologues of synaptobrevin/VAMP, syntaxin, synaptotagmin, and rab3. Antibodies
      generated to fusion proteins or to synthetic peptides encoded by the cloned cDNAs
      were used in an immunofluorescence assay to show that each of the cognate
      proteins are present in the cortex of the egg. A synaptobrevin/VAMP homologue
      appears to be specifically associated with the membrane of cortical granules
      before fertilization and, following cortical granule exocytosis, is incorporated
      into the plasma membrane of the zygote. A rab3 homologue is also associated with
      cortical granules specifically but, following fertilization, the protein
      reassociates with different, yet undefined, vesicles throughout the cytoplasm of
      the zygote. Homologues of synaptotagmin and syntaxin are also present at the egg
      cortex but, in contrast to rab3 and VAMP, appear to be associated with the plasma
      membrane. Following fertilization, syntaxin and tagmin remain associated with the
      plasma membrane and are more readily immunolabeled, presumably due to an
      increased accessibility of the antibodies to the target protein domains. We also
      show by immunoblotting experiments that the cognate proteins are of the sizes
      predicted for these homologues. These results suggest that at least some steps in
      the biology of cortical granules may be mediated by SNARE homologues, and this
      finding, along with the unique biology of cortical granules, should facilitate
      examination of specific events of the fertilization reaction and the mechanism of
      stimulus-dependent exocytosis.

PMID- 9266769
TI  - Calmodulin content, Ca2+-dependent calmodulin binding proteins, and testis
      growth: identification of Ca2+-dependent calmodulin binding proteins in primary
      spermatocytes.
AB  - In contrast with the transient pre-replicative increase in calmodulin (CaM) level
      observed in proliferative activated cells, postnatal development of rat testis
      was paralleled by 3 specific rises in CaM. The first one occurred between 5 and
      10 days, coincident with the appearance and proliferation start of spermatogonia
      and Sertoli cells. Meiosis accomplishment and spermatid differentiation were
      paralleled by 2 additional rises, at 24 and 32 days, respectively. The plateau
      phase of testis growth was coincident with the appearance of maturating
      spermatids and spermatozoa in the germinal epithelium, and with a decrease in CaM
      content. Testicular DNA:g wet tissue ratio reached the highest level in 15-day
      old rats and gradually decreased up to 35 days, when a constant level was
      reached. A similar level of Ca2+-CaMBPs was observed in 5- and 20-day-old rat
      testis. Although all subcellular fractions showed the ability to bind CaM in a
      Ca2+-dependent manner, CaM was mainly recovered in the nuclear and soluble
      fractions of adult and immature rat testis. Several Ca2+-CaMBPs with an apparent
      M(r) of 82, 75, 64, 19, and 14 kD were purified by affinity chromatography from
      pachytene primary spermatocyte nuclear matrix. Ca2+-CaMBPs showing an M(r) of
      120, 78, 72, and 66 kD were also purified from the supernatant obtained after DNA
      and RNA hydrolysis of meiotic nuclei. Major cytosolic Ca2+-CaMBPs of primary
      spermatocytes showed an M(r) of 120, 84, 44, and 39 kD. The functions that these
      Ca2+-CaMBPs might have during the first meiotic prophase is discussed.

PMID- 9266770
TI  - Ascidian eggs block polyspermy by two independent mechanisms: one at the egg
      plasma membrane, the other involving the follicle cells.
AB  - Many ascidians live in clumps and usually release sperm before the eggs.
      Consequently, eggs are often spawned into dense clouds of sperm. Because
      fertilization by more than a single sperm is lethal, ascidians have evolved at
      least two successive blocks to polyspermy: the rapid release of a glycosidase
      that inhibits sperm binding to the vitelline coat (VC) and a subsequent change in
      membrane potential that prevents supernumerary sperm-egg fusion. This paper shows
      that (1) these two blocks can be uncoupled by the use of suramin, and (2) most of
      the glycosidase appears to be from the follicle cells, which are accessory cells
      on the outside of the egg VC. Phallusia mammillata eggs initially bind numerous
      sperm but, after the glycosidase is released, only a few additional sperm bind.
      Intact eggs in 20 microM suramin release glycosidase, but the electrical response
      is inhibited; sperm swim actively and bind to the VC but fail to penetrate.
      Suramin treatment is completely reversible; intact eggs exhibit the electrical
      response an average of 11 minutes after the drug is washed out. Sperm must
      contact the follicle cells before passing through the VC; eggs with the VC
      removed and fertilized in the presence of 20 microM suramin show the electrical
      response 35% of the time, thus VC removal enhances sperm entry. Like the intact
      eggs, 100% of the naked eggs respond electrically to fertilization after the drug
      is washed out. Follicle cells that are isolated by calcium magnesium free
      seawater and then returned to complete seawater release N-acetylglucosaminidase
      activity in response to sperm. Thus, these eggs have two blocks to polyspermy
      that operate in sequence: an early first block resulting from enzymatic
      modification of the VC by N-acetylglucosaminidase released primarily from
      follicle cells and a second electrical block operating at the egg plasma membrane
      level and requiring sperm-egg fusion.

PMID- 9266771
TI  - Cocaine and amphetamine preferentially stimulate glutamate release in the limbic
      system: studies on the involvement of dopamine.
AB  - The effects of cocaine and d-amphetamine on extracellular glutamate and aspartate
      levels in the nucleus accumbens, prefrontal cortex, and striatum were studied by
      in vivo microdialysis in awake, freely moving rats. In the nucleus accumbens,
      glutamate levels were stimulated by cocaine (15-30 mg/kg, i.p.), GBR 12909 (15
      mg/kg, i.p.), and d-amphetamine (2 mg/kg, i.p.), while aspartate levels were not
      affected. The increase in nucleus accumbens glutamate levels following cocaine
      (30 mg/kg) was calcium-dependent and was blocked by pretreatment with dopamine
      antagonists; haloperidol (0.2 mg/kg, i.p.), SCH 23390 (0.02 mg/kg, i.p.), and
      raclopride (1 mg/kg, i.p.), as well as local 6-OHDA lesions of the nucleus
      accumbens. In the prefrontal cortex, glutamate levels were stimulated by both
      cocaine (15-30 mg/kg, i.p.) and d-amphetamine (2 mg/kg, i.p.), while aspartate
      levels were moderately stimulated by d-amphetamine only. The increase in
      prefrontal cortex glutamate levels following cocaine (30 mg/kg) was calcium
      dependent and was blocked by pretreatment with SCH 23390 (0.02 mg/kg, i.p.), but
      not haloperidol (0.2 mg/kg, i.p.) or raclopride (1 mg/kg, i.p.). In the striatum,
      glutamate and aspartate levels were not affected by either cocaine (15-30 mg/kg,
      i.p.) or d-amphetamine (2 mg/kg, i.p.). These findings demonstrate that
      stimulants enhance glutamate release in limbic brain structures, nucleus
      accumbens, and prefrontal cortex, but not extrapyamidal brain structures,
      striatum. Furthermore, the increase in glutamate release in the nucleus accumbens
      may be mediated by dopamine.

PMID- 9266772
TI  - NMDA and AMPA receptors in the lateral nucleus of the amygdala are postsynaptic
      to auditory thalamic afferents.
AB  - Projections from the medial geniculate body (MGB) to the lateral nucleus of the
      amygdala (LA) have been implicated in the conditioning of emotional reactions to
      acoustic stimuli. Anatomical and physiological studies indicate that this pathway
      uses the excitatory amino acid L-glutamate as a transmitter. Recent physiological
      studies have demonstrated that synaptic transmission in the thalamo-amygdala
      pathway requires the activation of both N-methyl-D-aspartate (NMDA) and alpha
      amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors, two of the
      major classes of ionotrophic glutamate receptors. In order to characterize the
      nature of thalamoamygdala interactions, we examined the synaptic associations
      between thalamic afferents and amygdala neurons that contain at least one
      glutamate receptor subtype. Thalamic afferents to the amygdala were identified by
      lesion-induced anterograde degeneration and anterograde transport of biotinylated
      dextran-amine, while postsynaptic glutamate receptors were labeled
      immunocytochemically using antisera directed the R1 subunit of the NMDA receptor
      and the GluR1 and GluR2/3 subunits of the AMPA receptors. Both methods
      demonstrated that the majority (77%) of thalamic afferents contact dendritic
      spines, and most (60%) of these spines express at least one glutamate receptor
      subtype. To a lesser extent, identified afferents also contacted small and large
      dendritic shafts, and many of these were immunoreactive. Thalamic afferents
      terminated on approximately the same proportion (60%) of immunoreactive targets
      for each glutamate receptor studied. These data provide morphological evidence
      that thalamic afferents directly synapse onto amygdala neurons that express
      glutamate receptors and suggest ways in which thalamic afferents activate and
      influence amygdala circuitry.

PMID- 9266773
TI  - Glutamate decarboxylase (GAD67 and GAD65) gene expression is increased in a
      subpopulation of neurons in the putamen of Parkinsonian monkeys.
AB  - The cellular distribution of the mRNAs encoding for the two isoforms of glutamate
      decarboxylase, GAD67 and GAD65, was analyzed by in situ hybridization
      histochemistry in the caudate nucleus and putamen of control and 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated parkinsonian squirrel monkeys.
      On brain sections processed with a radioactive and a digoxigenin-labeled cRNA
      probe, the GAD67 and GAD65 mRNAs were colocalized in virtually all labeled
      neurons of the caudate nucleus and putamen, in both control and MPTP-treated
      monkeys. Furthermore, neurons labeled with the GAD cRNAs constituted at least 90%
      of all striatal neurons, as estimated on adjacent Nissl-stained sections. In the
      two groups of monkeys, double-labeling experiments using a combination of
      radioactive GAD67 or GAD65 and digoxigenin-labeled preproenkephalin (PPE) cRNA
      probes showed that roughly half of all neurons labeled with the GAD cRNAs were
      also labeled with the PPE cRNA probe. When compared to controls, GAD67 and GAD65
      mRNA levels were higher in the putamen, and to a lesser extent in the caudate
      nucleus, of MPTP-treated monkeys. Further analysis of labeling at the cellular
      level in a dorsolateral sector of the putamen revealed that GAD67 and GAD65 mRNA
      levels in MPTP-treated monkeys were increased in PPE-labeled (presumed striato
      pallidal) neurons but not in PPE-unlabeled (presumed striato-nigral) neurons. Our
      results demonstrate that most neurons in the caudate nucleus and putamen of
      squirrel monkeys contain the mRNAs encoding for the two GAD isoforms. In
      addition, the selective increase in GAD mRNA levels in PPE-labeled neurons
      provides further evidence that striato-pallidal GABAergic neurons are hyperactive
      in MPTP-treated parkinsonian monkeys.

PMID- 9266774
TI  - Methamphetamine alters presynaptic glutamate immunoreactivity in the caudate
      nucleus and motor cortex.
AB  - It has been suggested that methamphetamine (METH)-induced neurotoxicity requires
      the activation of both dopamine (DA) and glutamate (GLU) systems. To investigate
      the possibility that METH-induced increases in extracellular GLU, as measured by
      in vivo microdialysis [Nash and Yamamoto (1992) Brain Res., 581:237-243], arise
      from neuronal stores, postembedding immunogold electron microscopy was used to
      measure the density of presynaptic GLU immunoreactivity within the striatum, the
      shell of the nucleus accumbens, and the motor cortex. Rats were treated with METH
      (5 mg/kg), or an equivalent volume of saline (SAL), every 2 h for a total of four
      injections. No ultrastructural evidence of terminal degeneration was observed.
      Significant decreases in the density of nerve terminal GLU immunolabeling
      occurred 12 h following METH administration within the primary motor cortex and
      the ventrolateral caudate/putamen, and a trend towards depletion was seen within
      the dorsolateral caudate/putamen. Although GLU immunolabeling within the shell of
      the nucleus accumbens was unaffected, DA content was decreased in all regions
      examined 1 week following METH treatment. The lack of degeneration, coupled with
      a partial recovery of DA levels, suggests that moderate doses of METH may inhibit
      DA biosynthesis without widespread terminal loss. Furthermore, METH
      administration results in a decrease in presynaptic GLU that correlates both
      temporally and anatomically with delayed GLU overflow, suggesting that neuronally
      derived GLU may play a role in METH-induced neurotoxicity. However, there does
      appear to be a dissociation between DA loss and altered GLU immunocytochemistry
      within the nucleus accumbens.

PMID- 9266775
TI  - Serotonin-1A antagonists attenuate the effects of nicotine withdrawal on the
      auditory startle response.
AB  - Withdrawal from the chronic administration of nicotine has previously been shown
      to lead to an enhanced auditory startle response in rats. In order to explore the
      neuropharmacology and neurophysiology underlying this phenomenon, we examined the
      effects of various 5-hydroxytryptamine (5-HT)-1A antagonists and agonists on the
      nicotine-withdrawal-enhanced auditory startle response in male rats. Animals were
      treated with nicotine (6 mg/kg/day nicotine base, via subcutaneously implanted
      osmotic minipumps) for 12 days. After 12 days the pumps were removed and the
      animals allowed to undergo spontaneous withdrawal for several days. In agreement
      with previous results, nicotine withdrawal led to a significant elevation of the
      auditory startle response. Pretreatment with the 5-HT-1A agonists (+)8-OH-DPAT
      (0.001-0.1 mg/kg) and LY274600 (0.3-3.0 mg/kg) either had no affect or
      exacerbated the nicotine-withdrawal-enhanced startle response. Pretreatment with
      the 5-HT-1A antagonists NAN-190 (1-3 mg/kg), LY206130 (1-10 mg/kg), or WAY-100635
      (0.1-1.0 mg/kg) blocked the increase in the startle response caused by nicotine
      withdrawal at doses that had no effect on baseline startle responses. These data
      indicate that 5-HT-1A receptors play a role in the neurophysiology of nicotine
      withdrawal. In addition, 5-HT-1A antagonists may be able to relieve some nicotine
      withdrawal symptoms in man and may represent a novel pharmacotherapy for smoking
      cessation.

PMID- 9266776
TI  - Methamphetamine selectively damages dopaminergic innervation to the nucleus
      accumbens core while sparing the shell.
AB  - Dopaminergic innervation to the nucleus accumbens was investigated following a
      neurotoxic regimen of methamphetamine (MA) treatment. Four 10 mg/kg doses of MA
      were administered s.c. to male Sprague-Dawley rats with a 2 h interval between
      doses. Rectal temperatures were monitored for the induction of MA-induced
      hyperthermia. Three days or 2 weeks after MA treatment the animals were
      sacrificed by transcardial perfusion and processed for tyrosine hydroxylase (TH
      IR) and glial fibrillary acidic protein immunoreactivity (GFAP-IR). MA treatment
      produced a severe loss of TH-IR throughout the striatum, including the nucleus
      accumbens. However, within the nucleus accumbens, there was substantial sparing
      of TH-IR in the shell, while in the core immunoreactivity was almost entirely
      lost. Furthermore, astrogliosis, as demonstrated by GFAP-IR, was prevalent in the
      core but present only in sparse patches in the medial and lateral shell. Thus,
      dopaminergic innervation to the nucleus accumbens core undergoes degeneration
      following MA treatment, while innervation to the shell is resistant to the
      neurodegenerative effects of MA.

PMID- 9266777
TI  - Digitalis Investigation Group (DIG) trial: a stimulus for further research.

PMID- 9266778
TI  - Effect of amlodipine on norepinephrine kinetics and baroreflex function in
      patients with congestive heart failure.
AB  - BACKGROUND: The use of calcium channel blocking drugs is controversial in heart
      failure, partly because of concerns about neurohormonal stimulation. Preliminary
      data suggest that the newer agent amlodipine may be useful in this syndrome.
      Suppression of sympathetic activity either directly or by sensitized baroreflex
      function could be contributing factors to the clinical use of this drug.
      OBJECTIVE: To assess the effect of short-term amlodipine therapy on baseline
      measures of sympathetic activity and baroreflex function in patients with chronic
      stable congestive heart failure (CHF). METHODS: Seven patients with chronic CHF
      (New York Heart Association functional class II or III, moderate to severe
      reduction in left ventricular systolic function) were studied. All patients
      underwent baroreflex testing with head-up tilt, head-down tilt, and head-down
      tilt with phenylephrine infusion. Heart rate, mean arterial pressure, forearm
      blood flow and resistance, and plasma norepinephrine (NE) kinetics were assessed
      at baseline and after each baroreflex perturbation on three occasions: a control
      test and after 10 days each of placebo and amlodipine therapy. RESULTS: Plasma NE
      and NE spillover did not significantly increase after amlodipine administration
      compared with control and placebo tests (488 +/- 119 pg/ml vs 350 +/- 85 and 325
      +/- 87 pg/ml). In three subjects, plasma NE levels were essentially unchanged,
      whereas in four they rose markedly (289 +/- 87 pg/ml at control vs 551 +/- 158
      pg/ml). There was no difference in the response of any variable during baroreflex
      perturbations after amlodipine administration compared with control and placebo
      tests. One subject who tolerated head-down tilt coupled with phenylephrine
      administration during the control and placebo tests became markedly short of
      breath during the same intervention after amlodipine administration. Plasma NE
      levels in this patient had risen markedly while receiving amlodipine and were not
      appropriately suppressed during the baroreflex loading maneuver. CONCLUSIONS:
      Short-term therapy with amlodipine does not suppress sympathetic activity or
      alter efferent responses to baroreflex perturbation in patients with stable
      chronic CHF. Significant increases in plasma NE and NE spillover and abnormal
      responses to baroreflex stimulation are possible after administration of this
      drug. The relevance of these findings to studies in larger number of patients
      requires further study.

PMID- 9266779
TI  - Short-term reproducibility of cardiopulmonary measurements during exercise
      testing in patients with severe chronic heart failure.
AB  - Eleven men with severe chronic heart failure (peak cardiac index 4.0 +/- 0.2
      L/m2/min), six on a heart transplantation waiting list, were prospectively
      assessed. To determine reproducibility of cardiopulmonary and hemodynamic
      variables for clinical purposes during ramp bicycle ergometry, the patients
      underwent two ramp bicycle ergometer tests (3 minutes unloaded, work rate
      increments of 12.5 W/min) with a 1-week interval between tests. Oxygen uptake
      (VO2) carbon dioxide production (VCO2), and ventilation were measured breath by
      breath, and calculations were performed to determine gas exchange ratio, oxygen
      pulse, ventilatory equivalents of oxygen and carbon dioxide, and end-tidal
      partial pressure for oxygen and carbon dioxide. Additionally, heart rate, blood
      pressure, and lactate levels were assessed. Measurements were performed at
      submaximum work rate levels of 25 W, 50 W, and 75 W at ventilatory threshold and
      at peak work rate. At all measurement points, the coefficient of variation for
      cardiopulmonary variables was between 1.4% and 7.1% for submaximum work rate
      levels, between 1.2% and 4.4% at ventilatory threshold, and between 2.4% and 7.1%
      at peak work rate. For heart rate, blood pressure, and lactate levels,
      coefficient of variation was between 2.7% and 5.7% for submaximum work rate
      levels, between 1.4% and 6.1% at ventilatory threshold, and between 1.2% and 5.5%
      at peak work rate. The data suggest high reproducibility for duplicate
      measurements of cardiopulmonary and hemodynamic variables during ramp bicycle
      ergometry in patients with severe chronic heart failure. The results may be used
      to determine whether any variable in a single patient is significantly different
      from that obtained in a previous exercise test or if the change is within
      experimental error.

PMID- 9266780
TI  - Effects of warfarin on markers of hypercoagulability in patients with heart
      failure.
AB  - Heart failure is associated with a hypercoagulable state. A single-center,
      randomized, double-blind, placebo-controlled trial was performed to test the
      hypothesis that warfarin will modify a hypercoagulable state in heart failure.
      This study included 76 patients with heart failure. At baseline, patients had
      evidence for a hypercoagulable state with elevated plasma levels of
      thrombin/antithrombin III (TAT) complexes (3.4 +/- 2.0 ng/ml), prothrombin
      fragment F1 + 2 (1.5 +/- 0.9 nmol/L), and D-dimers (630 +/- 401 ng/ml). Warfarin
      therapy (international normalized ratio [INR] 2.7 +/- 1.3) significantly
      decreased plasma levels of TAT complexes (p < 0.002), F1 + 2 (p < 0.001), and D
      dimers (p < 0.001) when compared with baseline values at 1, 2, and 3 months of
      therapy. In contrast, patients receiving placebo had persistent elevation of TAT
      complexes (p = not significant [NS]), F1 + 2 (p = NS), and D-dimers (p = NS)
      during follow-up at 1, 2, and 3 months. The two treatment groups followed
      different trends over time for all three markers (p < 0.001). The effect of low
      intensity warfarin (INR 1.3 +/- 0.08) versus moderate-intensity warfarin (INR 2.3
      +/- 1.1 ) on markers of hypercoagulability was evaluated in 14 patients. When
      compared with baseline, low-intensity warfarin administration decreased plasma
      levels of TAT complexes (p = NS), F1 + 2 (p = 0.05), and D-dimers (p = 0.04). In
      these patients F1 + 2 was further reduced with moderate-intensity warfarin (p <
      0.001). Our findings suggest that a hypercoagulable state in heart failure can be
      modified by warfarin therapy.

PMID- 9266781
TI  - Acute and long-term effects of the angiotensin-converting enzyme inhibitor,
      enalapril, on adrenergic activity and sensitivity during exercise in patients
      with left ventricular systolic dysfunction.
AB  - Patients with heart failure and left ventricular systolic dysfunction exhibit
      increased adrenergic activity but blunted adrenergic responsiveness. We studied
      patients enrolled in the Studies of Left Ventricular Dysfunction, examining
      exercise responses of heart rate (HR) and plasma norepinephrine (PNE). Eighty
      seven patients were studied before randomization; 65 of these were examined 1
      year after randomization to placebo or enalapril. Compared with prevention trial
      (asymptomatic) patients, patients in the treatment trial (symptomatic) had higher
      resting HR and PNE levels and less increase in HR with a greater increase in PNE
      with exercise. Acute administration of enalapril increased the resting HR in
      patients in the prevention trial only but had no significant effect on PNE. After
      1 year of therapy, patients in the prevention trial exhibited no change. Within
      the treatment trial, the placebo group displayed both a higher peak PNE and
      increase in PNE with exercise than did the enalapril group, whose HR response was
      maintained in spite of a reduction of exercise PNE. We conclude that (1) compared
      with asymptomatic patients, symptomatic patients with reduced left ventricular
      ejection fraction manifest greater resting and exercise adrenergic activity, with
      blunted HR response; and (2) in symptomatic patients, 1 year of enalapril
      treatment effected an augmented HR response to adrenergic stimulation, supporting
      an interaction between the renin/angiotensin and adrenergic nervous systems.
      Normalization of adrenergic tone and response likely contributes to the benefits
      of long-term angiotensin-converting enzyme inhibitor therapy.

PMID- 9266782
TI  - A randomized controlled trial of epoprostenol therapy for severe congestive heart
      failure: The Flolan International Randomized Survival Trial (FIRST).
AB  - This trial evaluated the effects of epoprostenol on patients with severe left
      ventricular failure. Patients with class IIIB/IV congestive heart failure and
      decreased left ventricular ejection fraction were eligible for enrollment if
      angiography documented severely compromised hemodynamics while the patient was
      receiving a regimen of digoxin, diuretics, and an angiotensin-converting enzyme
      inhibitor. We randomly assigned 471 patients to epoprostenol infusion or standard
      care. The primary end point was survival; secondary end points were clinical
      events, congestive heart failure symptoms, distance walked in 6 minutes, and
      quality-of-life measures. The median dose of epoprostenol was 4.0 ng/kg/min,
      resulting in a significant increase in cardiac index (1.81 to 2.61 L/min/m2), a
      decrease in pulmonary capillary wedge pressure (24.5 to 20.0 mm Hg), and a
      decrease in systemic vascular resistance (20.76 to 12.33 units). The trial was
      terminated early because of a strong trend toward decreased survival in the
      patients treated with epoprostenol. Chronic intravenous epoprostenol therapy is
      not associated with improvement in distance walked, quality of life, or morbid
      events and is associated with an increased risk of death.

PMID- 9266783
TI  - Public release of cardiac surgery outcomes data in New York: what do New York
      state cardiologists think of it?
AB  - BACKGROUND AND OBJECTIVE: Since 1990, risk-adjusted outcomes for patients
      undergoing coronary artery bypass graft surgery in New York state have been
      released to the public. The purpose of this study was to assess the extent to
      which referring cardiologists share these data with patients and use these data
      to make referrals. METHODS: A survey questionnaire was sent to all cardiologists
      in New York in the New York State Chapter of the American College of Cardiology.
      RESULTS: Four hundred fifty cardiologists responded to the survey. Most (94%)
      found the report "easy to read." A majority (67%) found the report to be "very
      accurate" or "somewhat accurate" in capturing differences in the performance of
      cardiac surgeons, whereas 33% found it to be "not at all accurate." Twenty-two
      percent reported that they "routinely discuss the reports with their patients,"
      and 38% responded that the information has affected their referrals to surgeons
      "very much" or "somewhat." CONCLUSIONS: A majority of cardiologists has not
      generally changed their well-established referral patterns as a result of the New
      York coronary artery bypass graft surgery reports. However, there has been a
      modest impact on referrals resulting from the distribution of these reports. The
      findings also suggest that increased dialogue between clinicians and policy
      makers regarding the format and structure of public releases would be a valuable
      undertaking.

PMID- 9266784
TI  - Significance of the Thrombolysis in Myocardial Infarction scoring system in
      assessing infarct-related artery reperfusion and mortality rates after acute
      myocardial infarction.
AB  - Thrombolysis in Myocardial Infarction (TIMI) flow scores were originally devised
      as semiquantitative angiographic measures of coronary artery perfusion. Several
      studies have indicated an important relation between different TIMI flow grades
      at 90 minutes after thrombolysis and clinical outcome. To further evaluate this
      relation we conducted a metaanalysis of all angiographic, postinfarction trials
      that studied the relation between individual 90-minute TIMI flow grades and
      mortality rates. In 4687 pooled patients, the mortality rate was lowest in
      patients with TIMI grade 3 flow (3.7%) and significantly lower than those with
      TIMI 2 (6.6%, p = 0.0003; odds ratio 0.55; 95% confidence interval [CI] 0.4% to
      0.76%) or TIMI 0/1 flow (9.2%, p < 0.0001; odds ratio 0.38; 95% CI 0.29% to
      0.5%). The mortality rate difference between TIMI grade 2 and TIMI grade 0/1
      patients was also significant (p = 0.02; odds ratio 0.7; 95% CI 0.51% to 0.94%).
      This study confirms the importance of achieving rapid and complete reperfusion
      after acute myocardial infarction with the best outcome associated with 90-minute
      TIMI 3 flow. Furthermore, it shows that although TIMI 2 flow (partial perfusion)
      is not equivalent to TIMI 3 flow, it nevertheless still confers a significant
      survival benefit compared with TIMI flow 0/1.

PMID- 9266785
TI  - Increasing age is a major risk factor for hemorrhagic complications after
      pulmonary embolism thrombolysis.
AB  - We reviewed our database of 312 patients with pulmonary embolism who received
      thrombolysis in five clinical trials. At baseline, none had a history of stroke,
      internal bleeding within 6 months, surgery within 10 days, or occult blood in
      stool. Sixty-six major bleeding episodes occurred within 72 hours of
      administering thrombolysis in 61 (20%) patients: bleeding at the catheterization
      site (34 cases), gross hematuria (9), intracranial hemorrhage (5), and 18 other
      bleeding episodes that led to at least a 10% hematocrit decrease. Patients with a
      major bleeding complication were on average older than patients with no
      hemorrhagic complication (mean age 62.9 +/- 1.9 years vs 56.2 +/- 1.1 years; p =
      0.005). In an adjusted analysis, there was a fourfold increased risk of bleeding
      among patients older than 70 years compared with patients younger than 50 years
      (relative risk [RR] 3.9; 95% confidence interval [CI] 1.7 to 8.9). By using age
      as a continuous variable, we found a 4% (RR 1.04; 95% CI 1.02 to 1.06) increase
      in risk of bleeding for each incremental year of age. In addition, patients with
      higher body mass index had an increased risk of bleeding. Patients who had
      undergone catheterization had a five times greater risk of bleeding (RR 5.2; 95%
      CI 1.5 to 17.8). In summary, increasing age, larger body mass index, and
      catheterization predisposed to bleeding complications after pulmonary embolism
      thrombolysis.

PMID- 9266786
TI  - Relation of gender to physician use of test results and to the prognostic value
      of stress technetium 99m sestamibi myocardial single-photon emission computed
      tomography scintigraphy.
AB  - We analyzed potential gender differences in the use and prognostic value of
      stress technetium 99m sestamibi tomography, image results, and cardiac event
      rates over a period of 15 +/- 8 months in 1226 men and 1151 women. Men had more
      abnormal tomographic images, but referral for catheterization and
      revascularization similarly increased in relation to the number of defects. Men
      and women with abnormal images had similar event rates, 19.6% and 18.2%,
      respectively, although men more often had myocardial infarction or cardiac death
      (7.6% vs 4.1 %, p < 0.05), whereas women had an increased likelihood of unstable
      angina or congestive heart failure (11.5% vs 7.6%, p < 0.05). Normal images
      predicted a low yearly rate of myocardial infarction or death: 1.7% for men and
      0.8% for women. Image findings, particularly defect extent, were independent
      predictors of events in both groups. Thus, after stress Tc-99m sestamibi single
      photon emission computed tomography perfusion imaging, there was no gender bias
      in referral for invasive procedures, and for both men and women image findings
      were strongly associated with prognostic outcome.

PMID- 9266787
TI  - Outcomes and cost implications of a clinical-based algorithm to guide the
      discriminate use of stress imaging before noncardiac surgery.
AB  - Approximately 8 million patients at risk for coronary artery disease undergo
      noncardiac surgery annually in the United States. This study defined the
      appropriateness and cost of evaluating these patients with stress imaging tests.
      Before noncardiac surgery, 178 consecutive patients were prospectively studied by
      stress imaging. Pretest cardiac risk (low, intermediate, high) was established by
      interviewing the referring physician and separately by a cardiologist on the
      basis of the nature of noncardiac surgery and Eagle's clinical criteria. Patients
      were followed-up for alterations in management and perioperative events until
      hospital discharge. Referring physicians and cardiologists identified low risk in
      24% and 54% of patients, respectively (p < 0.0001). Of 96 patients identified as
      low risk by cardiologists, 75 had minor surgery and 21 had major surgery, but no
      clinical risk factors. In the remaining 82 patients with major surgery, ischemia
      and other severe abnormalities were detected in 19 (23%) patients. At follow-up,
      no perioperative complications occurred in minor surgery; one patient with major
      surgery but no clinical risk factors died from complications related to
      hypertrophic cardiomyopathy. Patients with at least one clinical risk factor
      undergoing major surgery but who did not have ischemia on stress testing (n = 63)
      had two complications (infarction and unstable angina). Intervention
      (revascularization and surgical cancellation) was probably the explanation for
      the absence of events in 19 patients with ischemia. With a weighted mean Medicare
      reimbursement ($386), the use of a simple selection algorithm based on noncardiac
      surgery and clinical risk to avoid testing low-risk patients would have an
      average cost of $214 per patient, representing a 45% savings.

PMID- 9266788
TI  - Intravascular ultrasound assessment of regional aortic wall stiffness,
      distensibility, and compliance in patients with coarctation of the aorta.
AB  - BACKGROUND: Impaired aortic pulsatility has been demonstrated by angiography in
      children and in studies of experimental animals with coarctation of the aorta.
      OBJECTIVES: The purpose of this study was to assess regional aortic stiffness,
      distensibility, and compliance before and after balloon dilation in patients with
      coarctation of the aorta. METHODS AND RESULTS: Intravascular ultrasound
      examination was performed in 13 pediatric patients with the diagnosis of
      coarctation of the aorta to yield aortic diameter. Area transverse sections at
      both systolic and diastolic period were measured at three aortic levels: the
      proximal, distal, and coarctation segments. Balloon dilation was also performed
      in eight of 13 patients. By using pressures measured in the same areas, an aortic
      stiffness index (beta) was calculated as In(Ps/Pd)/(Ds-Dd), where In is natural
      logarithm, Ps is systolic pressure, Pd is diastolic pressure, Ds is systolic
      diameter, and Dd is diastolic diameter. Aortic distensibility and an estimation
      of aortic compliance were also calculated. The beta stiffness index of the
      coarctation and the proximal segments of the aorta were significantly greater
      than that of the distal segment of the aorta (p < 0.01). The aortic wall
      stiffness beta index did not acutely change after successful balloon dilation,
      but the distensibility and compliance of distal aorta were nonetheless
      significantly decreased after balloon dilation (p < 0.01, p < 0.05) as a function
      of changes of pulsatility of flow. CONCLUSIONS: Abnormal proximal aortic
      stiffness may be a strong contributing factor that promotes the genesis of
      hypertension in patients with coarctation even after successful repair or balloon
      angioplasty.

PMID- 9266789
TI  - Correlations between coronary flow reserve measured with a Doppler guide wire and
      treadmill exercise testing.
AB  - We compared exercise test results to a physiologic depiction of stenosis
      severity, coronary flow reserve (CFR), measured with a Doppler guide wire in 35
      patients with single-vessel coronary disease. Group 1 (n = 21) had abnormal CFR,
      and group 2 (n = 14) had normal CFR. In group 1, 14 of 21 had ST-segment
      depression versus 3 of 14 in group 2 (p < 0.01). Exercise treadmill time (Bruce
      protocol) was normalized to the age- and sex-predicted time. Exercise time and
      normalized exercise time were less in group 1 (5.6 +/- 2.3 vs 9.9 +/- 1.8 min and
      0.82 +/- 0.32 vs 1.25 +/- 0.23, p < 0.00001). Having either ST-segment depression
      or a normalized exercise time <1 during exercise had a 95% sensitivity, 71%
      specificity, and 86% predictive accuracy in identifying abnormal CFR. Coronary
      stenoses and minimal lumen diameter were similar in groups 1 and 2. By using
      stepwise logistical regression analysis, exercise time and ST-segment depression
      predicted CFR with a total r2 of 0.51. Minimal lumen diameter did not
      significantly add to the model. Exercise test variables, ST-segment depression,
      and exercise time are predictive of the physiologic significance of coronary
      lesions.

PMID- 9266790
TI  - Safety of early intravenous dipyridamole technetium 99m sestamibi SPECT
      myocardial perfusion imaging after uncomplicated first myocardial infarction.
      Early Post MI IV Dipyridamole Study (EPIDS).
AB  - We assessed the safety of early (2 to 4 days) intravenous dipyridamole infusion
      in conjunction with technetium 99m sestamibi tomographic myocardial perfusion
      imaging in patients with first myocardial infarction (MI). Early risk
      stratification with myocardial perfusion imaging of patients after acute MI may
      be useful to identify patients who either require further evaluation or may be
      safely discharged. Because of minimal hemodynamic effects, intravenous
      dipyridamole may be a safe means of producing hyperemia for myocardial perfusion
      imaging. Stable patients with first acute MI who met entry criteria were
      randomized (3:1) to either intravenous dipyridamole infusion (0.56 mg/kg over a 4
      minute period) 48 to 96 hours after onset of symptoms or a control (no test)
      group. Adverse cardiac events (unstable angina, recurrent MI, or cardiac death)
      were evaluated during and 24 hours after the dipyridamole infusion and during the
      corresponding 24 hours for the control group. Two hundred eighty-four patients
      received dipyridamole infusion a mean time of 3.3 +/- 0.7 days after MI. There
      were no adverse clinical events either during or immediately after the infusion.
      During the 24 hours after infusion, three patients had symptoms of unstable
      angina pectoris, one patient had a recurrent MI, and no patients died. The
      earliest event occurred 4.2 hours after the dipyridamole infusion. Three patients
      had unstable angina pectoris, whereas no patients had either recurrent MI or died
      in the control group. There were no statistically significant differences between
      the two groups. In a multicenter trial, dipyridamole infusion administered early
      after the first acute MI resulted in no increased evidence of cardiac events
      either immediately or 24 hours after the procedure compared with a control group.
      Therefore intravenous dipyridamole can be safely used as a pharmacologic
      vasodilator for myocardial perfusion imaging soon after uncomplicated MI.

PMID- 9266791
TI  - Long-lasting abnormalities in cardiac sympathetic nervous system in patients with
      coronary spastic angina: quantitative analysis with iodine 123
      metaiodobenzylguanidine myocardial scintigraphy.
AB  - Quantitative analysis of iodine 123 metaiodobenzylguanidine (MIBG) myocardial
      tomographic imaging showed that the regional uptake reduction and abnormally high
      washout of MIBG in the myocardial territories of the coronary artery with spasm
      were observed in 33 (75%) and in 30 (68%) of 44 patients with coronary spastic
      angina, whereas it was observed in two (7%) and in four (15%) of 27 control
      subjects, respectively. The patients with higher disease activity of the anginal
      attack and those with life-threatening ventricular arrhythmias were frequently
      associated with either the uptake reduction or the abnormally high washout of
      MIBG (91% in patients with high disease activity, 100% in patients with
      ventricular arrhythmias). The repeated studies of MIBG myocardial tomographic
      imaging at 2 and 6 months after suppression of anginal attacks by medical
      treatments showed that the scintigraphic abnormalities still remained in 85% of
      the patients at 2 months and 32% at 6 months. Thus the abnormalities in
      sympathetic nervous system assessed with MIBG scintigraphy has been shown to be
      highly associated with patients with coronary arteries with spasm, particularly
      high-risk patients, and lasted for several months despite suppression of anginal
      attack.

PMID- 9266793
TI  - Patient acceptance of reused angioplasty equipment.
AB  - The reuse of percutaneous transluminal coronary angioplasty (PTCA) balloon
      catheters has recently been proposed as a way of containing costs. Our aim was to
      examine patient acceptability of this strategy. We asked 100 consecutive patients
      scheduled for potential or definite PTCA whether they would permit the use of
      sterilized, reused balloon catheters. We collected demographic, clinical,
      angiographic, and insurance-status data on all patients. Sixty-eight patients
      responded that they would have allowed reused equipment (group 1). Thirty-two
      patients would have refused (group 2). Only three group 2 patients could be
      enticed to change their opinions by appealing to their altruism or self-interest.
      The two groups of patients could not be distinguished by any variable, including
      insurance status. We conclude that a sufficient number of patients would be
      willing to permit reused PTCA equipment for such programs to be implemented
      successfully from a logistic standpoint. However, the disapproval by one third of
      patients raises the possibility of adverse publicity and litigation for
      institutions using such strategies.

PMID- 9266792
TI  - Effect of informed consent on anxiety in patients undergoing diagnostic
      electrophysiology studies.
AB  - The process of informed consent has been suspected to raise patient anxiety, but
      this supposition has not been well studied or validated. The aim of this study
      was to evaluate the effect of a detailed informed consent protocol on patient
      anxiety. Fifty patients (36 men, 14 women, mean age 55 +/- 18 years) undergoing
      diagnostic cardiac electrophysiologic studies were enrolled. Patients were
      randomly assigned to receive either a consent that did not detail specific risks
      regarding the procedure (consent A) or one that detailed the risks (consent B).
      The Spielberger State-Trait Anxiety Inventory was administered before obtaining
      consent (state 1), immediately after the consent protocol (state 2), and after
      the electrophysiologic testing procedure, when the results of the test were known
      to the patient (state 3). Midazolam was administered during the procedure by
      staff who were blinded to the state/trait anxiety scores and the type of consent
      the patient had received. Patients receiving consent A had a significant decrease
      in state 2 anxiety compared with those who received consent B (adjusted mean
      difference 3.3; 95% confidence intervals 0.2 to 6.4). In the consent A group, 74%
      of patients received midazolam as opposed to 96% in the consent B group (p
      <0.02). Patients without inducible ventricular arrhythmias had a significant
      decrease in state 3 anxiety compared with those with inducible ventricular
      arrhythmias (adjusted mean difference 8.9; 95% confidence intervals 2.3 to 15.5).
      Thus detailed informed consent is associated with increased anxiety relative to a
      consent that does not detail specific risks. However, the difference in anxiety
      is mild and its clinical impact requires further exploration.

PMID- 9266794
TI  - Comparison of 6F with 7F and 8F guiding catheters for elective coronary
      angioplasty: results of a prospective, multicenter, randomized trial.
AB  - A group of 460 patients was considered in our prospective study of assessment of
      the efficiency and safety of 6F (internal diameter 0.062 inches) guiding
      catheters to perform elective percutaneous coronary angioplasty by the femoral
      approach by using conventional balloon systems. The patients were randomly
      assigned either a 6F guiding catheter (first group, n = 231; 247 coronary
      lesions), or a 7F or 8F guiding catheter (second group, n = 229; 252 coronary
      lesions). The exclusion criteria were the ongoing myocardial infarction, the
      marked reduction of left ventricular function, and the decision to treat the
      lesion with a device not fitting the 6F guiding catheter. The angioplasty success
      rates (87% in the 6F group vs 88% in the 7F or 8F group) and the stent
      implantation rates (21% vs 25%) were similar in both groups. The ischemic
      complication rates (death, 2 vs 1 ) were also similar. The incidence of the
      femoral complications was significantly less important in the 6F group than in
      the 7/8F group (13.8% vs 23.5%; p < 0.01). Significant differences also were
      noted for the procedural time (36 +/- 22 vs 41 +/- 28 min; p < 0.01), the
      fluoroscopy time (11 +/- 10 vs 14 +/- 4 min; p < 0.05), the volume of contrast
      injected (136 +/- 68 ml vs 168 +/- 95 ml; p < 0.0001), and the time of femoral
      compression after the introducer sheath removal (11.7 +/- 9 vs 14.1 +/- 12 min; p
      < 0.01). Our data suggest that 6F guiding catheters for elective coronary
      angioplasty are more effective than are the larger diameter catheters. Besides a
      significant decrease of vascular complications, angioplasty with a 6F guiding
      catheter reduces the procedural time and the amount of contrast.

PMID- 9266795
TI  - The influence of Pb2+ on expression of acetylcholinesterase and the acetylcholine
      receptor.
AB  - This paper examines the influence of inorganic lead (Pb2+) on the presence of
      acetylcholinesterase (AchE) molecular forms and the acetylcholine receptor (AchR)
      in two types of excitable tissue, primary cultures of skeletal muscle and neural
      retina from embryonic chick. Treatment of skeletal muscle with Pb2+ is observed
      to cause reductions in the 5/7S and 19S but not the 11.4S molecular forms of
      AchE. The reductions are dose-dependent, requiring submicromolar concentrations,
      slow in onset, requiring incubation times greater than 24 hr, and tissue
      specific, being pronounced in skeletal muscle but absent from neural retina.
      Significantly, the reductions in AchE occur without corresponding reductions in
      amounts of AchR and without reduction in activity of protein kinase C (PKC).
      These studies illustrate a tissue-specific action of inorganic lead that is not
      mediated through PKC.

PMID- 9266796
TI  - Inhibitory effect of new quinolones on GABA(A) receptor-mediated response and its
      potentiation with felbinac in Xenopus oocytes injected with mouse-brain mRNA:
      correlation with convulsive potency in vivo.
AB  - Convulsions induced by the interaction of new quinolone antimicrobial agents
      (NQs) and nonsteroidal anti-inflammatory drugs (NSAIDs) were previously reported,
      and blockade of GABA(A) receptor by NQs and its potentiation with NSAIDs were
      considered as one of its possible mechanisms. However, useful methodology for
      prediction of convulsive potencies of NQs with or without NSAIDs in vivo based on
      in vitro screening was not established. Therefore, we applied the Xenopus oocytes
      translation system of exogenous messenger RNA (mRNA) to examine the mechanism of
      convulsion induced by interaction of NQs and NSAIDs, and the relationship between
      convulsive potencies in vivo and inhibitory effect on GABA-induced current
      response in vitro was investigated. This system also has alternative possibility
      for the in vivo toxicological studies sacrificing innumerous animals. Glutamic
      acid, kainic acid, quisqualic acid, NMDA, and serotonin-induced currents were not
      modified by ENX of NQs and/or FLB of NSAIDs, while glycine- and ACh-induced
      currents were slightly inhibited. GABA (10 microM)-induced current was inhibited
      by norfloxacin (NFLX), ciprofloxacin, ENX, and ofloxacin (OFLX) with IC50 of 17,
      33, 58, and 280 microM, respectively. IC50 of NQs decreased to 1/3 (OFLX)-1/165
      (NFLX) in the presence of 10 microM FLB, while FLB did not modulate the GABA
      response in the absence of NQs. CSF concentration of ENX at the time of
      convulsion in clinical situation approximated the IC50 of ENX for the GABA
      response. The increase of incidence for NQs-induced convulsion by concomitant
      NSAIDs in vivo could also be explained by the potentiation of inhibitory effects
      of NQs with FLB in the normal range of CSF concentration of these drugs. We also
      examined convulsive potency (threshold dose for convulsion) in CNS by
      intracerebral infusion of NQs to mice with or without FLB pretreatment, and
      significant correlations between the convulsive potencies and IC50 of NQs for the
      GABA response were observed. These findings suggested that the blockade of GABA
      ersic neurotransmission in CNS is a dominant mechanism of convulsion induced by
      NQs and that the convulsant-adverse reaction of NQs in vivo may be predicted from
      the inhibitory effect on the GABA(A) receptor in vitro using the Xenopus oocytes
      translation system of exogenous mRNA.

PMID- 9266797
TI  - Effect of cadmium on Na-Pi cotransport kinetics in rabbit renal brush-border
      membrane vesicles.
AB  - Chronic exposure to cadmium impairs various renal functions, including phosphate
      (Pi) transport. To further investigate the mechanism of cadmium-induced
      alterations in renal Pi transport, kinetics of Na+-dependent Pi uptake were
      studied in renal cortical brush-border membrane vesicles (BBMV) exposed to CdCl2
      in vitro. BBMVs isolated from rabbit renal outer cortex were preincubated in a
      buffer containing CdCl2 (50 microM in most cases) for 60 min at 37 degrees C and
      then tested for Pi uptake at 25 degrees C. CdCl2 treatment resulted in a marked
      attenuation of Na+-dependent Pi uptake with no changes in Na+-independent Pi
      uptake and membrane permeability to Na+. CdMt treatment induced no changes in Pi
      transport. The inhibition required preincubation of vesicles with CdCl2 for more
      than 30 min and was not reversed by extravesicular EDTA, suggesting that cadmium
      affects the transport system at the internal side of the membrane. Kinetic
      analysis indicated that two sodium ions and one phosphate ion interact with a
      carrier, and this stoichiometry was not altered by cadmium treatment. Cadmium
      treatment did not change the apparent Km for Na+ (K(Na)) and that for phosphate
      (K(Pi)), but it markedly reduced the Vmax of the Na+-dependent Pi transport.
      These results indicate that exposure of proximal tubular brush border membranes
      to cadmium impairs the Pi transport capacity, probably by reducing the effective
      number of Na-Pi cotransporter units without altering substrate affinities of the
      carrier.

PMID- 9266798
TI  - 2'3'-Dideoxyinosine inhibits the humoral immune response in female B6C3F1 mice by
      targeting the B lymphocyte.
AB  - 2',3'-Dideoxyinosine (ddI) is a purine nucleoside analog currently being used for
      the treatment of HIV-positive individuals and patients with AIDS. Preliminary
      immunotoxicity studies have shown that a consequence of ddI treatment in female
      B6C3F1 mice is the inhibition of the humoral immune response. This effect was
      dose dependent in a range of 100 to 1000 mg/kg with a no observed adverse effect
      level of less than 100 mg/kg for a 28-day treatment period. These studies were
      undertaken to investigate the immune cell target of ddI and to determine the
      mechanism of this toxicity. B6C3F1 mice were treated with 1000 mg/kg/day by oral
      gavage for 28 days. The B lymphocyte was identified as the cellular target of ddI
      through separation-reconstitution experiments of the adherent and nonadherent
      cell populations and of the T and B lymphocyte populations. These studies
      revealed a deficit in the ability of the nonadherent cells from ddI-treated mice
      to mount a normal antibody response to sRBC. A further separation of the
      nonadherent cells into T and B cells revealed a decreased ability of ddI-treated
      B cells to develop specific humoral immunity. Additional studies were undertaken
      to determine the mechanism by which ddI is affecting the B cell. Surface marker
      analysis of splenocytes revealed no difference in the cell populations between
      vehicle- and ddI-treated mice. B cell proliferation was also unaffected as shown
      by incubation with either a polyclonal stimulator, lipopolysaccharide, or anti
      IgM plus IL-4. These results indicate that the primary cellular target of ddI is
      the B lymphocyte.

PMID- 9266799
TI  - Mercuric ion inhibits the activity and fidelity of the human cell DNA synthesome.
AB  - Mercuric ion is cytotoxic and mutagenic to cells; however, the mechanisms of
      mercuric ion-induced cytotoxicity are not well understood. Numerous studies have
      suggested that these effects may be due in part to the alteration and inhibition
      of a variety of cellular processes including DNA replication, DNA repair, RNA
      transcription, and protein synthesis. Studies utilizing whole cells to examine
      these activities are not able to specifically identify the precise mechanism or
      site of the effect. Other studies carried out using whole cell extracts and
      variously purified DNA polymerases are not able to adequately represent the
      highly ordered environment in which DNA replication occurs in the intact cell. We
      report here, for the first time, the use of an intact human cell multiprotein
      complex (which we have termed the DNA synthesome) to carry out full-length DNA
      replication and DNA synthesis in the presence of Hg2+ ion in vitro. In this study
      we report that DNA replication and DNA polymerase activity, as well as DNA
      replication fidelity of the human cell DNA synthesome, are specifically inhibited
      by physiologically attainable concentrations of mercuric ion.

PMID- 9266800
TI  - Role of 3,4-dichlorophenyl methyl sulfone, a metabolite of o-dichlorobenzene, in
      the changes in hepatic microsomal drug-metabolizing enzymes caused by o
      dichlorobenzene administration in rats.
AB  - 2,3- and 3,4-Dichlorophenyl methyl sulfoxides and 2,3- and 3,4-dichlorophenyl
      methyl sulfones (2,3- and 3,4-DCPSO2Mes) were detected in the urine of rats
      administered o-dichlorobenzene (o-DCB). After administration of o-DCB to rats,
      swift decreases were observed in the concentrations of o-DCB in blood, liver, and
      kidneys, whereas 3,4-DCPSO2Me appeared in blood, liver, kidneys, and adipose
      tissue. The concentrations of 3,4-DCPSO2Me in the blood and three tissues reached
      maxima at 24 hr. Both aminopyrine N-demethylase and aniline hydroxylase
      activities and cytochrome P450 content of hepatic microsomes decreased 24 hr
      after administration of o-DCB. In contrast, 3,4-DCPSO2Me increased the activities
      of these enzymes and cytochrome P450 and b5 contents in rat liver microsomes. In
      both antibiotic-pretreated and bile duct-cannulated rats dosed with o-DCB, the
      concentrations of 2,3- and 3,4-DCPSO2Mes in blood, liver, kidneys, and adipose
      tissue were dramatically reduced. These findings suggest that the process of
      formation of methylsulfonyl metabolites of o-DCB involves biliary secretion of
      DCPSO2Mes and/or their precursors which will be subjected to metabolism by
      intestinal microflora. In antibiotic-pretreated rats, the inhibitory effects of o
      DCB administration on the activities of aminopyrine- and aniline-metabolizing
      enzymes and the contents of cytochromes P450 and b5 in hepatic microsomes were
      greater than those observed in the intact rats. In bile duct-cannulated rats, the
      decrease in aminopyrine N-demethylase activity after administration of o-DCB was
      greater than that observed in the intact rats. These findings suggest that the
      apparent inhibition of drug-metabolizing enzymes by o-DCB is the result of
      simultaneous contrary effects, namely, the inductive effect of 3,4-DCPSO2Me and
      the stronger inhibitory effect of an unknown factor(s) on drug-metabolizing
      enzymes.

PMID- 9266801
TI  - Fish oil-feeding prevents perfluorooctanoic acid-induced fatty liver in mice.
AB  - The effects of perfluorooctanoic acid (PFOA) on the levels of lipids in liver and
      serum were compared between mice fed a diet supplemented with soy bean oil (SO),
      perilla oil (PO), or fish oil (FO) for 4 weeks. Hepatic content of triglyceride
      (TG) was significantly lower in the mice fed the FO diet than that in the mice
      fed either the SO or the PO diet. The treatment with PFOA caused a marked
      accumulation of TG in the livers of SO-fed and PO-fed mice (seven- and twofold
      over their respective controls), whereas a level of TG remained low in the mice
      fed the FO diet. Incorporation in vivo of [3H]glycerol revealed that FO-feeding
      reduced synthesis of TG in the liver. The administration of PFOA increased the
      incorporation of [3H]glycerol into hepatic phospholipid (PL) regardless of the
      dietary oil, while synthesis of hepatic TG from [3H]glycerol was not altered by
      the treatment with PFOA. Serum level of TG was reduced by the administration of
      PFOA to the mice fed either the SO diet or the PO diet, while no change in the
      level was observed in the mice fed the FO diet. These results suggest that the
      accumulation of TG in the livers of PFOA-treated mice is due to the inhibition of
      the secretion of TG into circulation. PFOA-induced hepatic accumulation of TG is
      prevented by the feeding of the FO diet which inhibits TG formation. Among three
      dietary oils, FO-feeding alone prevented the PFOA-caused accumulation of TG in
      the liver. The importance of docosahexaenoic acid (22:6(n - 3)) is discussed in
      relation to the prevention of fatty liver induced by chemicals.

PMID- 9266802
TI  - Nitric oxide-mediated vasorelaxation induced by sodium polyoxyethylene
      laurylether sulfate.
AB  - Ingestion of surfactants is known to cause hemodynamic changes with decreased
      total vascular resistance. Motivated by this clinical observation, we
      investigated the direct effects of a common anionic surfactant, sodium
      polyoxyethylene laurylether sulfate (LES), on isolated ring segments of rat
      thoracic aorta. LES did not produce any vasocontractile responses, but relaxed
      ring segments precontracted with 10(-6) M phenylephrine in a concentration
      dependent manner. This LES-induced vasorelaxation was significantly reduced by
      the removal of endothelium or pretreatment with N(G)-nitro-L-arginine methylester
      hydrochloride, methylene blue, or oxyhemoglobin to the same degree, but was not
      affected by pretreatment with indomethacin. A further study measuring NO2- plus
      NO3- (NO(x), total metabolites of NO) in the medium of calf pulmonary artery
      endothelial (CPAE) cells, a cultured cell line, revealed that LES caused a
      significant increase in NO(x) production. On the other hand, in a study measuring
      intracellular Ca2+ in fura-2-loaded CPAE cells, LES caused a significant increase
      in intracellular Ca2+. These results suggest that LES causes endothelium
      dependent vasorelaxation via a NO-mediated signaling pathway, which might be due
      to Ca2+ mobilization.

PMID- 9266803
TI  - A physiologically based pharmacokinetic (PB-PK) model for 1,2-dichlorobenzene
      linked to two possible parameters of toxicity.
AB  - A physiologically based pharmacokinetic (PB-PK) model was developed for 1,2
      dichlorobenzene (1,2-DCB) for the rat. This model was adjusted for the human
      situation, using human in vitro parameters, including a Vmax and Km determined
      with human microsomes. For comparison, the Vmax and Km values from the rat were
      scaled allometrically to the human case. The model was used in two ways: (1)
      Acute hepatotoxicity was related to the amount of reactive metabolites (epoxides)
      formed in vitro. For rats, the hepatic concentration of epoxide metabolites in
      vivo after exposure to a toxic dose level (250 mg/kg bw) was predicted using in
      vitro parameters. For man, the dose level needed to obtain the same toxic liver
      concentration of reactive metabolites as in rat was predicted, assuming a
      concentration-effect relationship in the liver. It could be concluded that this
      concentration is not reached, even after induction of the oxidation step, due to
      saturation of metabolism and a concomitant accumulation of 1,2-DCB in fat. (2)
      Hepatotoxicity was related to depletion of glutathione (GSH) in the liver. In the
      model, the consumption of hepatic GSH by metabolism (based on in vivo and in
      vitro data) and normal turnover was described. In vivo validation was conducted
      by comparing the predictions of the model with the results of a GSH depletion
      study performed at two dose levels (50 and 250 mg/kg bw). Subsequently, the GSH
      consumption by 1,2-DCB metabolites was estimated for man using human in vitro
      metabolic data. GSH turnover in human liver was assumed to be the same as that in
      rat. It appeared that at a dose level of 250 mg/kg, hepatic GSH was completely
      depleted after 10 hr for man, whereas for the rat a maximum depletion of 75% was
      predicted, after 15 hr. The presented model provides a quantitative tool for
      evaluating human risk for two different toxicity scenarios, namely covalent
      binding of reactive metabolites and depletion of GSH.

PMID- 9266804
TI  - Development of a physiologically based pharmacokinetic model to describe the
      disposition of methanol in pregnant rats and mice.
AB  - Physiologically based pharmacokinetic (PBPK) models have been developed in recent
      years to describe the disposition of xenobiotics during gestation. These models
      can account for the dynamics of physiologic changes associated with pregnancy and
      represent a significant advantage in quantitatively assessing potential exposure
      of the conceptus. The PBPK approach was used to develop a model of methanol
      disposition during gestation in rats and mice. To validate this model,
      concentrations of methanol in the dam and the conceptus were determined after
      methanol exposure of rats on Gestational Day (gd) 14 and 20 and of mice on gd 18.
      At the developmental stages examined, the model provided a good description of
      methanol disposition in the maternal circulation and the conceptus of both
      species. Furthermore, the model was capable of providing good fits to methanol
      concentration-time data from the literature. In pregnant animals,
      conceptal/maternal AUC and Cmax ratios decreased with increasing dose at both gd
      14 and gd 20 in the rat and at gd 18 in the mouse. Additionally, the
      conceptal/maternal diffusion constant ratio consistently decreased with
      increasing dose in pregnant rats and mice. These results are consistent with
      earlier observations that methanol limits its own delivery to the conceptus.
      Further experimentation is required to continue the process of developing a
      generalized PBPK model to describe the disposition of xenobiotics in pregnancy,
      to examine specific mechanisms of nonlinear conceptal methanol disposition, and
      to expand the model to extrapolate to low-dose human exposures.

PMID- 9266805
TI  - Characterization of intracellular calcium responses produced by polycyclic
      aromatic hydrocarbons in surface marker-defined human peripheral blood
      mononuclear cells.
AB  - Previous studies have demonstrated that polycyclic aromatic hydrocarbons (PAHs),
      such as benzo[a]pyrene (BaP) and 7,12-dimethybenz[a]anthracene (DMBA), and
      possibly 2,3,7,8-tetrachlorodibenzo(p)dioxin (TCDD), may exert their
      immunosuppressive effects by altering intracellular Ca2+ homeostasis in
      lymphocytes. In these studies, we examined the effects of two immunosuppressive
      PAHs (BaP and DMBA), two nonimmunosuppressive PAHs (benzo[e]pyrene (BeP) and
      anthracene (ANTH)), and TCDD on intracellular Ca2+ levels in surface marker
      defined human peripheral blood mononuclear cells (HPBMC). BaP and DMBA, but not
      BeP and ANTH, were found to produce a time-dependent increase in intracellular
      Ca2+ with maximal effects achieved following 42- to 66-hr exposures. In a series
      of studies with HPBMC obtained from 10 donors exposed in vitro for 42 hr, BaP and
      DMBA were found to produce a significant increase in Ca2+ in CD3+ T cells, CD19+
      B cells, and CD14+ monocytes. BeP and ANTH did not produce a statistically
      significant increase in Ca2+ in the group of donors, but occasionally produced an
      apparent nonspecific elevation of Ca2+ in HPBMC from individual donors.
      Interestingly, TCDD produced a small and statistically significant increase in
      Ca2+ only in B cells analyzed for the pooled 10 donors. Certain BaP metabolites,
      such as the 7,8-dihydrodiol and the 7,8-diol-9,10-epoxide, were more effective in
      elevating Ca2+ in HPBMC lymphocytes at 20 hr than was BaP. These results
      demonstrate in normal HPBMC that immunosuppressive PAHs alter intracellular Ca2+
      homeostasis in B cells, T cells, and monocytes, and suggest that P450 metabolism
      may play an important role in the immunotoxicity of certain PAHs.

PMID- 9266806
TI  - Acrolein-induced cell death in human alveolar macrophages.
AB  - Acrolein is an environmental air pollutant that is known to suppress respiratory
      host defense against infections. The mechanism of the decrease in host defense is
      not yet clear. In this study, the effects of acrolein on human alveolar
      macrophages and their function were examined. Acrolein caused dose-dependent
      cytotoxicity to alveolar macrophages as demonstrated by the induction of
      apoptosis and necrosis. In addition, at lower doses, acrolein caused induction of
      heme oxygenase 1 protein; however, stress protein 72 (SP72) was not induced.
      These findings demonstrated that acrolein caused a dose-dependent selective
      induction of a stress response, apoptosis, and necrosis in human alveolar
      macrophages. Macrophage function was assessed by release of cytokines in response
      to endotoxin stimulation. Acrolein caused a dose-dependent inhibition of release
      of IL-1beta, TNF-alpha, and IL-12. The inhibition of cytokine release and
      cytotoxicity to alveolar macrophages may in part be responsible for acrolein
      induced immunosuppression of the lung.

PMID- 9266807
TI  - In vitro uptake of methyl tert-butyl ether in male rat kidney: use of a two
      compartment model to describe protein interactions.
AB  - Methyl tert-butyl ether (MTBE) is a gasoline additive that causes renal tumors in
      male rats. In the process of measuring chemical specific parameters necessary to
      develop a quantitative dosimetry model of MTBE in rats, the uptake of MTBE was
      found to be 5.5 times greater in male than in female F-344 rat kidney homogenate.
      The objectives of this study were to characterize the factor(s) that influences
      the high uptake of MTBE into male rat kidney in vitro and to develop a system to
      evaluate the interaction of MTBE with the male rat-specific protein, alpha 2u
      globulin (alpha 2u). The uptake of MTBE in male, but not female, rat kidney
      homogenate was found to be dependent on protein and chemical concentrations. When
      [14C]MTBE was incubated with male rat kidney homogenate, radioactivity coeluted
      with the total protein fraction on a gel filtration column. An interaction
      between [14C]MTBE and male rat kidney proteins was not found under conditions of
      dialysis or anion exchange chromatography. A two-compartment vial equilibration
      model was used to assess the interaction between MTBE and alpha 2u. Using this
      system, the dissociation constant for MTBE and alpha 2u was estimated to be 2.15
      x 10(-4) M, which is in the range of other chemicals known to bind to alpha 2u
      and cause alpha 2u-mediated nephropathy. d-Limonene oxide was used to validate
      this two-compartment vial equilibration system. These findings illustrate a
      technique useful in estimating the dissociation constant for a volatile chemical
      and a protein, as well as explain the process that contributes to the uptake of
      MTBE into male rat kidney homogenate in vitro. A description of the weak
      interaction between MTBE and alpha 2u will be used to refine a physiologically
      based pharmacokinetic model to describe the target tissue (kidney) concentrations
      of MTBE.

PMID- 9266809
TI  - The diabetogenic effects of acute verapamil poisoning.
AB  - Verapamil poisoning is known to produce hyperglycemia and metabolic acidosis in
      humans. The purpose of this study was to elucidate mechanisms of verapamil
      induced hyperglycemia in awake dogs. Mongrel canines were chronically
      instrumented to permit studies in the conscious state. In six healthy dogs,
      steady-state glucose infusion requirement after 1 hr of insulin infusion at 1000
      mU/min was 19 +/- 1 mg/kg/min. In six separate dogs, verapamil toxicity was
      induced via verapamil infusion in the portal vein; during verapamil toxicity, the
      glucose infusion requirement with an insulin infusion rate of 1000 mU/min was
      significantly decreased (3 +/- 1 mg/kg/min; p < 0.05, unpaired t test). Eleven
      other verapamil-toxic dogs were also treated with either saline (n = 6, 3.0
      ml/kg/hr) or glucagon (n = 5, 10 microg/kg/min). Insulin concentrations were not
      changed vs basal concentrations in either group. Catecholamine concentrations
      increased at least 15-fold in all groups (from 458 +/- 169 to 6973 +/- 480 pg/L
      in the saline-treated group). Glucose concentrations increased in saline-treated
      animals from 3.7 +/- 0.3 to 11.2 +/- 1.0 micromol/L, and with glucagon treatment,
      increased from 3.3 +/- 0.3 to 16.1 +/- 1.6 micromol/L (p < 0.05 vs saline,
      ANOVA). Verapamil poisoning appears to produce hyperglycemia by inducing systemic
      insulin resistance, blocking insulin release, together with an intact stress
      hormone response and glucogenic capacity.

PMID- 9266808
TI  - Influence of beta-naphthoflavone and methoxychlor pretreatment on the
      biotransformation and estrogenic activity of methoxychlor in channel catfish
      (Ictalurus punctatus).
AB  - The organochlorine pesticide methoxychlor [1,1,1-trichloro-2,2-bis(4
      methoxyphenyl) ethane] (MXC) has been classified as a proestrogen in mammals and
      fish, requiring demethylation prior to eliciting estrogenic activity or binding
      to the estrogen receptor. While microsomal demethylation occurs readily in the
      liver of fish, little is known about the enzyme(s) responsible or the effect of
      cytochrome P450 (CYP) inducers, other than those of CYP1A and CYP2K, on
      biotransformation. Consequently, male channel catfish were pretreated with MXC or
      beta-naphthoflavone (BNF), alone and in combination, to determine their effects
      on CYP protein expression, MXC biotransformation by hepatic microsomes,
      microsomal protein binding, and MXC estrogenic activity as determined by serum
      vitellogenin and 17beta-estradiol. Liver microsomes of both treated and untreated
      mature male catfish catalyzed formation of monodemethylated MXC, bisdemethylated
      MXC, as well as ring-hydroxylated metabolites. Pretreatment with BNF did not
      affect MXC metabolite profiles, overall rates of MXC biotransformation, or
      microsomal proteins recognized by anti-trout CYP2K1, but had the expected effect
      of inducing CYP1A and associated ethoxyresorufin O-deethylase activity. By
      contrast, pretreatment with MXC, alone or in combination with BNF, significantly
      reduced rates of MXC biotransformation and binding to liver microsomal protein.
      MXC/BNF cotreatment followed by MXC significantly induced serum vitellogenin,
      whereas MXC treatment alone led to a nonsignificant increase in vitellogenin and
      a significant increase in serum 17beta-estradiol. Thus, estrogenic activity
      elicited by cotreatment with MXC and BNF can occur despite diminished capacity of
      liver microsomes to catalyze formation of estrogenic demethylated metabolites or
      metabolites that bind microsomal protein. Possible mechanisms of MXC-induced
      attenuation of CYP-dependent metabolism are discussed.

PMID- 9266810
TI  - Cocaine detoxification by human plasma butyrylcholinesterase.
AB  - The ability of human plasma butyrylcholinesterase (BChE) to detoxify cocaine in
      vivo was evaluated. Intravenous administration of BChE, at doses sufficient to
      increase the plasma levels of the enzyme as much as 800-fold, produced no adverse
      effects on the cardiovascular, autonomic, or central nervous systems of rats.
      Most of the enzyme could be recovered in the plasma immediately after
      administration and remained active with a beta-t(1/2) of 21.6 +/- 2.4 hr.
      Pretreatment of chloralose-urethane anesthetized rats with BChE, 0.1-7.8 mg/kg,
      decreased the hypertensive and arrhythmogenic effects produced by cocaine and
      increased the lethal dose of cocaine by three- to fourfold. Treatment of
      conscious rats with 1 and 10 mg/kg BChE decreased the incidence of seizures and
      deaths produced by a prior dose of cocaine (80 mg/kg, i.p.). These results
      suggest that BChE would provide a safe and highly efficacious treatment for
      cocaine intoxication.

PMID- 9266811
TI  - Therapeutic use of butyrylcholinesterase for cocaine intoxication.
AB  - The most common complications of cocaine ingestion are on the cardiovascular and
      central nervous systems and produce chest pain and generalized seizures. In
      humans, decreased levels of butyrylcholinesterase (BChE) (EC 3.1.1.8) have been
      associated with sustained effects of cocaine and life-threatening complications.
      Administration of purified human BChE has previously been demonstrated to protect
      against cocaine-associated cardiovascular toxicity in rats. A shift in the
      metabolism of cocaine as well as enhanced metabolism may be the underlying
      mechanism of the enzyme. Therefore, levels of the parent drug and four
      metabolites were determined in rat plasma after i.p. administration of a lethal
      cocaine dose, followed by i.v. administration of BChE. Plasma and brain
      concentrations of cocaine were lowered by 80% after BChE administration.
      Furthermore, the metabolic profile of cocaine in the plasma was altered. The
      concentration of ecgonine methylester was doubled although the concentration of
      ecgonine, a secondary metabolite of cocaine, was reduced. The level of
      benzoylecgonine was reduced by one-half while norcocaine was absent. Cocaine
      associated effects upon the central nervous system were also shown to be reduced
      by administration of BChE to conscious rats. Furthermore, our studies in the cat
      have also shown that purified BChE shifts the metabolic profile of cocaine (1
      mg/kg) to the pharmacologically inactive products ecgonine methylester and
      ecgonine. Pretreatment with BChE (0.27, 1.0, and 10.0 mg/kg) ameliorated the
      hypertensive effects of cocaine (1 mg/kg) by reducing the duration and the extent
      of BP elevation by 66%. Administration of the enzyme, 1 min after cessation of
      cocaine infusion, resulted in an immediate attenuation in the cocaine-induced
      broadening of the QRS complex. These results suggest that BChE could be an
      effective and rapid therapy for the treatment of life-threatening cocaine-induced
      cardiovascular effects in human while clearing the total body burden of cocaine.

PMID- 9266812
TI  - A fluoroquinolone antibiotic with a methoxy group at the 8 position yields
      reduced generation of 8-oxo-7,8-dihydro-2'-deoxyguanosine after ultraviolet-A
      irradiation.
AB  - We have previously reported that two fluoroquinolone antibiotics gave rise to 8
      oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) in DNA of cells concurrently exposed
      to UV-A and that this correlated with clinical phototoxicity. To determine the
      structural basis for generation of oxidative damage, the ability of two synthetic
      fluoroquinolone candidate antibiotics, Bayer 12-8039 (12-8039) and Bayer Y3118
      (Y3118), to give rise to 8-oxo-dG in cultured liver epithelial cells was
      compared. 12-8039 contains a methoxy group at the 8 position of the quinolone
      nucleus, whereas Y3118 contains a chlorine group at the same position. Y3118
      produced dose-dependent increases in 8-oxo-dG formation in cultured cells after
      UVA irradiation, whereas the 8-OCH3-substituted 12-8039 produced no increase.
      Also, after exposure to 20 J/cm2 UVA, UV spectral scans of both compounds
      revealed that Y3118 underwent photodegradation whereas 12-8039 was stable. These
      results demonstrate that the presence of an 8-OCH3 group on the quinolone nucleus
      is important for the reduction of photogeneration of oxidative DNA damage and
      photodegradation in the presence of UVA irradiation. From this, we suggest that
      12-8039 has little phototoxic potential.

PMID- 9266813
TI  - Computer simulation of inspiratory airflow in all regions of the F344 rat nasal
      passages.
AB  - Data from laboratory animal experiments are often used in setting guidelines for
      safe levels of human exposure to inhaled materials. The F344 rat has been used
      extensively in laboratory experiments to determine effects of exposure to inhaled
      materials in the nasal passages. Many inhaled materials induce toxic responses in
      the olfactory (posterior) region of the rat nasal passages. The location of major
      airflow routes has been proposed as playing a dominant role in determining some
      olfactory lesion location patterns. Since nasal airflow patterns differ
      significantly among species, methods are needed to assess conditions under which
      these differences may significantly affect extrapolation of the effects of local
      dose in animals to potential disease outcome in humans. A computational fluid
      dynamics model of airflow and inhaled gas uptake has been used to predict dose to
      airway walls in the anterior F344 rat nasal passages (Kimbell et al., Toxicol.
      Appl. Pharmacol., 1993; 121, 253-263). To determine the role of nasal airflow
      patterns in affecting olfactory lesion distribution, this model was extended to
      include the olfactory region. Serial-step histological sections of the nasal
      passages of a F344 rat were used to construct the computer model. Simulations of
      inspiratory airflow throughout the rat nasal passages were consistent with
      previously reported experimental data. Four of the five major simulated flow
      streams present in the anterior nose (dorsal lateral, middle, ventral lateral,
      and ventral medial streams) flowed together to exit ventrally at the
      nasopharyngeal duct, bypassing the ethmoid recesses. The remaining dorsal medial
      stream split to flow both medially and laterally through the olfactory-epithelium
      lined ethmoid recesses in a Z-shaped pattern when viewed sagitally. Simulated
      flow in the ethmoid recesses was more than an order of magnitude slower than flow
      in the anterior and ventral parts of the nasal passages. Somewhat higher volumes
      of flow were predicted in the dorsal medial stream when the nasal vestibule was
      reshaped to be upturned, and more flow was allocated to the dorsal medial stream
      with increased inspiratory airflow rate, suggesting that rats may be able to
      allocate more airflow to this stream by both modifying the shape of the nasal
      vestibule and increasing inhaled air velocity during sniffing. The present study
      provides the first description of flow in the complex olfactory region of the
      nose of the F344 rat. This model will be used to evaluate the role of airflow
      patterns in determining the distribution of xenobiotically induced olfactory
      mucosal lesions. This information, combined with models of disposition in the
      airway lining, will provide comprehensive dosimetry models for extrapolating
      animal response data to humans.

PMID- 9266814
TI  - Dosimetry of chlorinated quinone metabolites of pentachlorophenol in the livers
      of rats and mice based upon measurement of protein adducts.
AB  - The dosimetry of chlorinated quinones arising from metabolism of
      pentachlorophenol (PCP), in the livers of male Sprague-Dawley rats and B6C3F1
      mice was investigated via measurements of cysteinyl protein adducts and estimates
      of the second-order reaction rate constants between the quinones and the
      proteins. We had previously shown that adducts of tetrachloro-1,4-benzoquinone
      (Cl4-1,4-BQ) and tetrachloro-1,2-benzosemiquinone (Cl4-1,2-SQ) were observed at
      the highest levels in the livers of Sprague-Dawley rats to which PCP had been
      administered by gavage (5-40 mg/kg body wt) (Biomarkers 1, 232-243, 1996). In the
      current study we observed that adducts of Cl4-1,4-BQ and tetrachloro-1,2
      benzoquinone (CL4-1,2-BQ) were predominant in the livers of B6C3F1 mice receiving
      20 mg PCP/kg body wt. The second-order rate constants, representing in vitro
      reactions between Cl4-1,2-BQ and Cl4-1,4-BQ and various cysteine residues of
      hepatic proteins of liver cytosol and liver nuclei, were estimated to be 0.012
      1.96 L(g protein)(-1) hr(-1) in rats and 0.082-1.67 L(g protein)(-1) hr(-1) in
      mice. The estimated tissue doses of the quinones to liver cytosol decreased in
      the order rat Cl4-1,4-BQ > mouse Cl4-1,4-BQ > mouse Cl4-1,2-BQ and to liver
      nuclei in the order mouse Cl4-1,2-BQ > mouse Cl4-1,4-BQ > rat Cl4-1,4-BQ. The
      corresponding doses of Cl4-1,2-SQ could not be inferred due to our inability to
      estimate the second-order rate constants. After aggregating the estimated
      contributions of all quinone species, mice had a fourfold greater dose to liver
      nuclei than rats, whereas rats had a threefold greater dose to liver cytosol. The
      increased nuclear dose to mouse liver compared to that of the rat suggests that
      the mouse is at greater risk to hepatic DNA damage from PCP-derived quinones.
      Investigation of the time course of levels of unconjugated
      tetrachlorohydroquinone (Cl4HQ) in the livers indicated that about 0.4% of Cl4HQ
      was oxidized to Cl4-1,4-BQ in both rats and mice.

PMID- 9266815
TI  - Cardiovascular effects of a herbicide containing glufosinate and a surfactant: in
      vitro and in vivo analyses in rats.
AB  - A herbicide, Basta (BASTA), containing glufosinate ammonium (GLA) as the main
      component and an anionic surfactant, sodium polyoxyethylene alkylether sulfate
      (AES), causes hemodynamic changes characterized by a decrease in total vascular
      resistance with an increase or a decrease in cardiac output in human acute oral
      poisoning. With a motivation based on these clinical observations, we tried to
      elucidate the exact component and its mode of action that is mostly responsible
      for the direct cardiovascular effects of this herbicide formulation,
      investigating the effects of BASTA, GLA, and AES independently on the
      cardiovascular system in rats in vitro and in vivo. In isolated right atria
      beating spontaneously in Krebs-Ringer's solution, BASTA and AES produced negative
      chronotropic responses in a concentration-dependent manner. In electrically
      driven isolated left atria, BASTA and AES produced positive inotropic responses
      concentration dependently but negative inotropic responses at extremely high
      concentrations. In aortic ring segments, BASTA and AES produced no
      vasoconstrictive effects but exerted significant vasodilative effects when the
      aortic ring was precontracted with phenylephrine. These in vitro responses caused
      by BASTA and AES occurred to a similar degree. On the other hand, the main
      component, GLA, produced no effects in isolated atria and aortas. In anesthetized
      rats, relatively low doses of BASTA and AES produced a decrease in blood pressure
      followed by a slight increase in heart rate, which was presumably due to
      baroreflex caused by the decrease in blood pressure. At an extremely high dose,
      BASTA and AES produced a decrease in blood pressure with a marked decrease in
      heart rate. These in vivo responses to BASTA and AES also occurred to a similar
      degree. In contrast, the main component, GLA, did not produce any effects on
      heart rate and blood pressure in anesthetized rats. From these results, we
      concluded that the effects of BASTA in our in vivo experiments were not caused by
      the main component, GLA, but was mostly caused by AES through its vasodilative
      effects plus cardiostimulatory effects at low doses and cardiosuppressive effects
      at high doses.

PMID- 9266816
TI  - Serine-enhanced restoration of 2-methoxyethanol-induced dysmorphogenesis in the
      rat embryo and near-term fetus.
AB  - Effects of serine on restorative growth were characterized by comparing
      embryo/fetal responses after maternal exposure to 2-methoxyethanol (ME) and ME +
      serine by gavage on gestation day (gd) 13, a day of heightened limb sensitivity.
      Paws (gd 20) and limb buds (gd 15) were examined after ME alone at 50, 100, and
      250 mg/kg, and after ME (either 100 or 250 mg ME/kg) + serine (1734 mg serine/kg)
      administered within minutes (0 hr) to 24 hr after ME. Paw development was not
      altered after ME at 100 mg/kg, but was highly sensitive to 250 mg ME/kg with all
      fetuses and litters exhibiting defects (ectrodactyly, syndactyly, and short
      digit) in the preaxial region. In contrast, the limb bud displayed dose-related
      incidences of abnormalities after maternal treatment with the low and high levels
      of ME. The condensing (precartilaginous, pentadactyl pattern) and noncondensing
      (undifferentiated mesenchymal cells) regions exhibited changes in their size,
      number, and location. Serine administration after 250 mg ME/kg was effective in
      reducing the occurrence of paw dysmorphogenesis with its protection potency
      inversely related to its delay of administration (i.e., 0% paw defect incidence
      after 0-hr delay, 25% after 4-hr delay, 41-45% after 8- and 12-hr delays, and 76%
      after 24-hr delay). The occurrences of limb bud pattern disturbances produced by
      ME were also markedly decreased by serine cotreatment. Higher incidences of
      embryonic defects versus those of fetal defects demonstrate that restorative
      growth followed ME exposure. Serine attenuation of ME teratogenicity appears to
      emanate from enhanced restorative growth so that tissue damage, which otherwise
      would be expressed as a defect at parturition, is repaired and replaced to resume
      development of the limb toward its normal structure.

PMID- 9266817
TI  - Mechanisms for the pancreatic oncogenic effects of the peroxisome proliferator
      Wyeth-14,643.
AB  - Several peroxisome proliferators have been shown to produce pancreatic acinar
      cell hyperplasia/adenocarcinomas in 2-year bioassays with rats: ammonium
      perfluorooctanoate (C8), clofibrate, methylclofenapate, HCFC-123, and Wyeth
      14,643 (WY). We have used in vitro (C8, WY) and in vivo (WY) approaches to
      examine several possible mechanisms of pancreatic tumorigenesis by peroxisome
      proliferating compounds. These mechanisms include cholecystokinin receptor
      agonism (CCK(A)), trypsin inhibition, alterations in gut fat content,
      cholestasis, and altered bile flow/composition. All of these mechanisms enhance
      pancreatic growth either by binding to the CCK(A) receptor or by increasing
      plasma CCK levels. In vitro experiments using a receptor competition binding
      assay demonstrated that WY and C8 do not bind directly to the CCK(A) receptor. In
      a continuous spectrophotometric assay, WY and C8 also failed to inhibit trypsin,
      a common mechanism for increasing plasma CCK levels. These in vitro results
      suggested that WY was not acting via the two most common mechanisms for
      modulation of pancreas growth. Two types of in vivo experiments were conducted.
      The subchronic study (2-month duration) was designed primarily to detect early
      changes in pancreatic growth such as those mediated by compounds that inhibit
      trypsin or act as CCK(A) receptor agonists. The chronic study (6 months) was
      designed primarily to evaluate whether the pancreatic lesions were secondary to
      hepatic changes such as cholestasis and/or altered bile flow/composition. In the
      in vivo experiments, male Crl:CDBR rats were fed diets containing 0 or 100 ppm
      WY. In the subchronic study WY-treated rats had a twofold increase in mean
      relative liver weights, an eightfold increase in hepatic peroxisomal
      proliferation, and a fourfold increase in hepatocyte cell proliferation after 1
      week which remained elevated throughout the 2 months of treatment. In contrast,
      no pancreatic weight effects, increases in plasma CCK, or acinar cell
      proliferation was seen through 2 months in the WY group when compared to the
      control group. Fecal fat concentrations were also measured at 2 months and
      demonstrated no difference between control and WY-treated animals. The absence of
      any early pancreas changes in the subchronic study is consistent with the in
      vitro data which demonstrated that WY is not a CCK(A) agonist or a trypsin
      inhibitor. The chronic study demonstrated increases in pancreatic weights at 3
      months (6% above control) and 6 months (17% above control), as well as increased
      CCK plasma levels in the WY-treated group. Liver effects in the chronic study
      paralleled those of the subchronic time points. Clinical pathology endpoints
      including increased serum concentrations of bile acids, alkaline phosphatase, and
      bilirubin were indicative of cholestasis in the chronic WY-treated group. The
      cholestasis may be responsible for the downward trend in total bile acid output,
      both of which may contribute to the modest increases in plasma CCK levels. These
      results indicate that chronic exposure to WY causes liver alterations such as
      cholestasis, which may increase plasma concentrations of CCK. Hence, WY may
      induce pancreatic acinar cell adenomas/adenocarcinomas via a mild but sustained
      increase in CCK levels secondary to hepatic cholestasis.

PMID- 9266818
TI  - Formation of novel C1-oxidised abasic sites in alkylperoxyl radical-damaged
      plasmid DNA.
AB  - We have recently shown that peroxyl radicals react with DNA to form alkali-labile
      sites. To further characterise these lesions, we studied their susceptibility to
      digestion by repair endonucleases that recognise different types of abasic sites.
      We found that peroxyl radical-damaged pSP189 plasmids were resistant to cleavage
      by T4 endonuclease V, an enzyme that incises DNA at "regular" and C4-oxidised
      abasic residues. In contrast, the DNA was digested by exonuclease III, an enzyme
      that recognises "regular" and C1-oxidised abasic sites. The presence of Trolox
      during exposure to peroxyl radicals reduced subsequent DNA cleavage by
      exonuclease III, while prior incubation of damaged plasmids with methoxyamine
      potentiated digestion by this enzyme. These findings suggest that peroxyl radical
      induced DNA damage involves the generation of novel C1-oxidised deoxyribose
      residues.

PMID- 9266819
TI  - Cyclophilins are induced by hypoxia and heat stress in myogenic cells.
AB  - This is a novel study demonstrating that cyclophilins are heat and stress
      inducible proteins in eukaryotic myogenic cells. We investigated the expression
      of cyclophilins in embryonal rat heart derived H9c2 myocytes following heat
      stress and chronic hypoxia. We report here that cyclophilins, the proteins
      capable of catalysing the interconversion of cis and trans isomers (PPIses) in
      proteins and peptides, are heat and stress inducible, and are involved in the
      complex stress response, as their level is significantly elevated after heat
      stress and hypoxia. A time course analysis showed the gradual increase in
      expressed levels of cyclophilin after heat stress of cells, with maximal
      expression as measured by Western blot at 48 hours after the actual treatment.
      Rat myogenic cells exposed to chronic hypoxia followed by 5 hours reoxygenation
      resulted in approximately threefold expression of PPI-ases. The results showing
      that cyclophilins are heat and stress inducible suggest a multiple role for
      cyclophilins in ischemia: a potential functional association with the different
      heat shock proteins, with the established protective role in ischaemic injury, as
      well as the possible involvement of cyclophilins in the protein folding in
      cooperation with molecular chaperones.

PMID- 9266820
TI  - Phospholipase D involvement in the plant oxidative burst.
AB  - Pathogen-triggered generation of reactive oxidants, termed the oxidative burst,
      contributes to disease resistance in both plant and animal kingdoms. Since
      phospholipase D plays a key role in the neutrophil oxidative burst signaling
      cascade and is highly abundant in plants, we investigated its participation in
      the plant oxidative burst. Thin layer chromatography of extracted phospholipids
      revealed no changes in phosphatidic acid levels in soybean cells undergoing
      oxidant production, and no changes in phosphatidyl-ethanol biosynthesis could be
      detected when ethanol was present during elicitation. An inhibitor of
      phosphatidic acid hydrolase, propranolol, did not modify burst parameters or
      phosphatidic acid levels during the burst, suggesting our inability to detect
      phosphatidic acid accumulation was not due to rapid elimination. Furthermore,
      exogenous phosphatidic acid did not elicit a burst or enhance elicitor-stimulated
      bursts. Finally, ethanol, a substitute nucleophile, did not abrogate the burst.
      With data showing the presence of phospholipase D in soybean cells, these data
      argue that soybean phospholipase D does not participate in signaling the
      oxidative burst. This constitutes the first major difference between the plant
      and animal oxidative burst signal transduction pathways.

PMID- 9266821
TI  - Characteristics of glutathione-capped ZnS nanocrystallites.
AB  - The titration of increasing equivalents of inorganic sulfide into preformed Zn
      glutathione led to the appearance of UV/VIS spectral features attributable to ZnS
      nanocrystallites. Glutathione-ZnS complexes upon irradiation caused reduction of
      methylviologen confirming their semiconductor properties. Size-fractionation of
      glutathione-ZnS samples on a gel filtration column showed the formation of a
      range of complexes whose spectral properties were correlated with the sulfide
      content. The stoichiometry of Zn:glutathione increased from 1:2 to a maximum of
      about 7:1 as the sulfide/Zn ratios increase from 0 to approximately 1.0 in Zn
      glutathione complex indicating up to 14-fold increase in the Zn-binding capacity
      of glutathione upon sulfide incorporation. Spectral characteristics of GSH-capped
      ZnS nanocrystallites were significantly influenced by pH and by the stoichiometry
      of Zn, sulfide and glutathione in the complex. Samples containing least
      glutathione and highest sulfide showed maximal luminescence at pH 6, whereas
      those with higher glutathione and lower sulfide content showed maximal
      luminescence at pH 11.

PMID- 9266822
TI  - Inhibition of the topoisomerase II-DNA cleavable complex by the ortho-quinone
      derivative of the antitumor drug etoposide (VP-16).
AB  - Etoposide (VP-16) is a widely used anticancer drug whose toxicity involves
      poisoning of topoisomerase II. VP-16 undergoes enzymatic oxido-reductive
      transformations in cells, resulting in the formation of the ortho-quinone
      derivative (VPQ) as a major product. The actions of VP-16 and VPQ on purified
      human topoisomerase II have been compared. Both the parent drug and VPQ are very
      efficient at trapping the topoisomerase II-DNA cleavable complex, suggesting that
      methoxy groups on the E-ring are not a prerequisite for activity. Our data also
      imply that VPQ has more effect than VP-16 on the breakage-reunion equilibrium of
      topoisomerase II and DNA. The stronger inhibition of the religation of the second
      strand observed with VPQ suggests it interacts asymmetrically with the two
      homodimers of topoisomerase II bound to DNA.

PMID- 9266823
TI  - Evidence for involvement of NF-kappaB in the transcriptional control of COX-2
      gene expression by IL-1beta.
AB  - The cyclooxygenase (COX) isoforms COX-1 and COX-2 convert arachidonic acid to
      prostaglandin (PG) precursors and are a limiting step in PG production.
      Interleukin-1beta (IL-1beta) treatment of type II A549 cells increases PGE2
      synthesis via transcription- and translation-dependent induction of COX-2. IL
      1beta produces a 10-fold induction of COX-2 mRNA and an 8-fold increase in COX-2
      transcription that was temporally preceded by activation of the transcription
      factor nuclear factor-kappaB (NF-kappaB). The protein-tyrosine phosphatase
      inhibitor phenylarsine oxide (PAO) prevented both NF-kappaB activation and
      induction of COX-2 mRNA. We show that two putative NF-kappaB motifs, kappaBu (
      447/-438) and kappaBd (-224/-214), from the COX-2 promoter bind p50/p65 NF-kappaB
      heterodimers in an IL-1beta-dependent manner and that the upstream element has
      the greater affinity. Finally, we demonstrate that the two NF-kappaB subunits,
      p50 and p65, synergistically activate a -917/+49 COX-2 promoter construct. We
      conclude that IL-1beta stimulates PG production via transcriptional activation of
      COX-2 and provide evidence that this may involve NF-kappaB.

PMID- 9266824
TI  - Resolution of the phytanic acid alpha-oxidation pathway: identification of
      pristanal as product of the decarboxylation of 2-hydroxyphytanoyl-CoA.
AB  - The structure and enzymology of the phytanic acid alpha-oxidation pathway have
      long remained an enigma. Recent studies have shown that phytanic acid first
      undergoes activation to its coenzyme A ester, followed by hydroxylation to 2
      hydroxyphytanoyl-CoA. In this paper we have studied the mechanism of
      decarboxylation of 2-hydroxyphytanoyl-CoA in human liver. To this end, human
      liver homogenates were incubated with 2-hydroxyphytanoyl-CoA in the presence or
      absence of NAD+. Hereafter, the medium was analyzed for the presence of pristanal
      and pristanic acid by gas chromatography mass spectrometry. Our results show that
      pristanal is formed from 2-hydroxyphytanoyl-CoA. Pristanal is subsequently
      oxidized to pristanic acid in a NAD+ dependent reaction. These results finally
      resolve the mechanism of the phytanic acid alpha-oxidation process in human
      liver.

PMID- 9266825
TI  - Beta amyloid toxicity does not require RAGE protein.
AB  - It has been suggested that a receptor for advanced glycation end products (RAGE)
      is the nerve cell receptor for amyloid beta protein (A beta). To determine if
      this is indeed the case, two neural cell lines as well as rat cortical neurons
      were examined for the presence of the mRNA for RAGE by PCR and northern blot
      analysis. Although lung was strongly positive, in no case was RAGE mRNA detected
      in the cultured neural cells. Glycated-albumin is a major ligand for RAGE and the
      cell surface RAGE protein is trypsin sensitive. In agreement with the mRNA data,
      trypsin treatment did not alter A beta toxicity, nor did glycated albumin modify
      the A beta response. It follows that RAGE is not the neural receptor for A beta.

PMID- 9266826
TI  - Expression of dihydropyridine binding sites in renal epithelial cells.
AB  - It has recently been shown that rabbit kidney epithelial cells (proximal tubule)
      possess two dihydropyridine (DHP)-sensitive calcium entry channels (1, 2). To
      evaluate the properties of the DHP binding sites, the binding of the DHP,
      [3H]PN200-110, was studied in epithelial cell membrane fractions (proximal
      tubule) of rabbit kidney cortex. High-affinity binding sites for the DHP were
      observed in both basolateral and apical membranes and in a membrane microsomal
      preparation from rabbit primary cultures of proximal tubule cells (cultured PT).
      In an extended analysis of the basolateral membrane preparation, two high
      affinity binding sites were evident with binding dissociation constants, Kd, of
      0.005 and 0.75 nM. The Kd values are similar to that observed for L-type calcium
      channel alpha1-subunits. Using a homology-based cloning strategy, a 388-base
      fragment of an alpha1-subunit was cloned from RNA isolated from rabbit cultured
      PT cells and freshly isolated proximal tubules and found to encode a protein
      identical to the cardiac form of the L-type alpha1-subunit (alpha1C-subunit). It
      is concluded that renal epithelial cells express high-affinity dihydropyridine
      receptors and that the receptors may be components of plasma membrane calcium
      channels, including L-type calcium channels, that control calcium entry in these
      cells.

PMID- 9266827
TI  - Subunit of glycosylation-inhibiting factor is an abundant protein that binds to
      certain glycoproteins and sugars.
AB  - 12 kDa subunit of glycosylation-inhibiting factor (GIF) is an abundant protein
      that can be isolated to homogeneity from different mammalian organs by successive
      application of the carboxymethylcellulose cation exchanger CM52, preparative flat
      bed isoelectrofocusing and repeated application of CM52-cellulose. Several
      isoforms of the 12 kDa GIF subunit exist in mammalian tissues. Conformational
      stability of two isoforms of a 12 kDa porcine GIF subunit have been studied by
      CD. Conformation of the protein remains stable within the range 20 degrees to 60
      degrees C. Over 60 degrees C the protein undergoes irreversible denaturation. The
      12 kDa GIF subunit is not stable within the pH range 2 to 3, adopts quasi-native
      structure within the pH range 3.5 to 5 while it remains stable between the pHs 6
      to 10. The 12 kDa GIF subunit strongly binds to CM52-cellulose from which it can
      be eluted at concentrations of NaCl higher than 0.6 M. The GIF subunit may also
      be eluted from the modified cellulose using certain glycoproteins and sugars.
      High abundance of the 12 kDa GIF subunit in different mammalian tissues and its
      capacity to bind certain glycoproteins and sugars may suggest that the protein
      might be involved in regulatory mechanisms of glycoprotein transport (chaperone
      for glycoproteins) and modulation of interactions between secreted glycoproteins
      and the cell surface receptors.

PMID- 9266828
TI  - The nuclear receptor corepressor SMRT inhibits interstitial collagenase (MMP-1)
      transcription through an HRE-independent mechanism.
AB  - Nuclear receptors inhibit synthesis of collagenase-1 (matrix metalloproteinase-1;
      MMP-1), an enzyme that degrades interstitial collagens and contributes to joint
      pathology in rheumatoid arthritis. SMRT (Silencing Mediator for Retinoid and
      Thyroid hormone receptors) mediates the repressive effect of nuclear receptors at
      hormone responsive elements (HREs), prompting us to investigate whether this co
      repressor could also regulate transcription of MMP-1, which lacks any known HREs.
      We find that primary synovial fibroblasts express SMRT. When over-expressed by
      transient transfection, SMRT inhibits MMP-1 promoter activity induced by
      interleukin-1 (IL-1), phorbol phorbol myristate acetate (PMA) or v-Src. SMRT
      apparently inhibits MMP-1 gene expression by interfering with one or more
      transcriptional elements clustered in a region between -321 and +63. We conclude
      that SMRT negatively regulates MMP-1 synthesis through a novel, HRE-independent
      mechanism that involves proximal regions of the MMP-1 promoter.

PMID- 9266829
TI  - A method for preparation, storage, and activation of large populations of
      immotile sea urchin sperm.
AB  - Reversible protein phosphorylation is associated with initiation and modulation
      of sperm flagellar motility. Many studies aimed at examining the signal
      transduction mechanisms underlying the expression of motility have relied on
      detergent-permeabilized sperm reactivated with exogenous 32P-ATP. However, the
      reactivation conditions allow variable levels of motility to be expressed and
      phosphorylation of many proteins that appear to be unrelated to sperm motility.
      Thus, identification of the few relevant proteins is difficult. We have developed
      a method to collect and keep sperm immotile until reactivated for analysis to
      normal motility levels. Artificial sea water (ASW) buffered with 5 mM 2-[N
      morpholino]ethanesulfonic acid at pH 6.0 and containing 50 mM KCl allows
      collection and storage of immotile sea urchin sperm for up to 96 h at 4-5 degrees
      C. Motility under these conditions is essentially zero, but sperm is rapidly
      reactivated to normal motility by diluting with ASW to standard pH (8.0) and KCl
      concentration (10 mM).

PMID- 9266830
TI  - Transport of alpha-ketoisocaproate in neuroblastoma NB-2a cells.
AB  - Transport of alpha-ketoisocaproate (KIC), a ketoacid originating from leucine and
      proposed to be involved in the buffering of glutamate in neurones, was studied in
      neuroblastoma NB-2a cells. The accumulated KIC was mostly transaminated to
      leucine, while free keto-acid was detectable either only after prolonged times or
      after inhibiting transaminase with aminooxyacetate. Accumulation of KIC was found
      to be inhibited by other branched-chain ketoacids, while lactate and beta
      hydroxybutyrate were ineffective. The transport of KIC, resembling a facilitated
      diffusion, was decreased by phloretin, alpha-cyano-4-hydroxycinnamate, 4,4'
      diisothiocyano-2,2'-stilbenedisulphonate, and p-chlorimercuribenzoate. The
      process of accumulation did not resemble a symport with protons; therefore an
      involvement of the known proton-coupled monocarboxylate transporters (MCT) was
      excluded. Distribution of KIC suggests a mechanism involving a cotransport with 2
      [Na+].

PMID- 9266831
TI  - Acute exposure to 25-hydroxy-cholesterol selectively reduces GABAb and not GABAa
      receptor-mediated synaptic inhibition.
AB  - Intracellular recording techniques were used to study the effects of the
      cholesterol oxide, 25-hydroxycholesterol (25-OH-Chol), on gamma-aminobutyric acid
      (GABA) receptor-mediated inhibitory postsynaptic potentials (IPSPs) in brain
      slices of the rat lateral septum. Superfusion of 25-OH-Chol increased the peak
      amplitude of the GABAa IPSP in more than half of the neurons tested, many of
      which exhibited a similar increase in the GABAb IPSP. However, some neurons
      exhibited a gradual decrease in input resistance and a selective reduction or
      blockade of the GABAb IPSP during prolonged exposure. Cholesterol partly mimicked
      the effects of 25-OH-Chol. These findings indicate that 25-OH-Chol can
      selectively reduce or block metabotropic GABAb while sparing ionotropic GABAa
      receptor-mediated synaptic inhibition. Our results indicate that brain slices can
      be used to study the effects of short term alterations in cholesterol on the
      excitability and synaptic integration properties of neurons.

PMID- 9266832
TI  - Dog CREM transcription factors: cloning, tissue distribution, and identification
      of new isoforms.
AB  - CREM (cAMP Response Element Modulator) transcription factors are involved in the
      cAMP-dependent transcriptional regulation of CRE-containing genes. Multiple CREM
      transactivators and repressors are generated from a single gene by alternative
      splicings and use of an alternative intronic promoter. Here we report the cloning
      and sequencing of the full-length dog CREM cDNA, corresponding to the CREMtau
      alpha splice variant. Amino acid sequence identity with mouse and human orthologs
      reached 94.5% and 91.0% respectively. Using the RNAse Protection Assay (RPA)
      method with three distinct probes, we analyzed the expression of the various CREM
      transcripts in several dog tissues. We showed that CREM transcription factors
      have a restricted tissue distribution and that the ratio between activators and
      repressors varies considerably from one tissue to another. Moreover, we
      amplified, by RT-PCR, a cDNA that corresponds to two new CREM isoforms and
      confirmed, by RPA experiments, the presence of these mRNAs in dog thyroid and in
      other tissues. These transcripts result from splicing of the gamma domain and
      encode potential CREM transactivators (CREMtau alphagamma and CREMtau2
      alphagamma).

PMID- 9266833
TI  - Cloning and functional analysis of new members of STAT induced STAT inhibitor
      (SSI) family: SSI-2 and SSI-3.
AB  - Upon the corresponding ligand's stimulation, the cytokine receptors activate
      several signal pathways: JAK-STAT pathway, Ras-MAP kinase pathway and so on.
      Recently, we demonstrated that one of the STAT3 (signal transducer and activator
      of transcription-3) target genes could suppress the function of STAT3 and
      designated as SSI-1(STAT induced STAT inhibitor-1). SSI-1 is thought to play a
      critical role in negative feedback control of JAK-STAT signaling pathway. In the
      present study, we identified two novel human genes which products have homologous
      region in their SH2 domain and its COOH-terminal region to mouse SSI-1. Northern
      blotting analysis and functional studies demonstrated that SSI-2 and SSI-3 mRNA
      were also induced by cytokine stimulation and their forced expression in mouse
      myeloid leukemia cell, M1, suppressed the apoptotic effect of LIF, like SSI-1. We
      also demonstrated the structure of human SSI-1.

PMID- 9266834
TI  - A novel zebrafish gene expressed specifically in the photoreceptor cells of the
      retina.
AB  - We have identified and characterized a novel protein from adult zebrafish retina,
      which we named ES1. Database search revealed that the ES1 gene has significant
      similarity to two genes with unknown functions: the Escherichia coli sigma cross
      reacting protein 27a (scrp27a) and the human KNP-I/GT335. In situ hybridization
      and immunohistochemistry experiments showed that both ES1 mRNA and protein are
      expressed specifically in adult photoreceptor cells. ES1 seems to be a
      cytoplasmic protein. An ES1-like antigen was also detected in photoreceptor cells
      of goldfish with anti-ES1 antibodies. The retina specific expression and the
      evolutionary conservation suggest that ES1 protein may be important for
      maintaining normal retina structure and function.

PMID- 9266835
TI  - The competitive binding of STAT3 and NF-kappaB on an overlapping DNA binding
      site.
AB  - Interleukin-1 (IL-1) and interleukin-6 (IL-6), two early-response cytokines
      expressed during an acute inflammatory reaction, regulate the expression of
      several acute phase proteins (APP) in the liver. IL-1 relays its signal to
      specific genes via NF-kappaB, whereas IL-6 sends its signal to the nucleus via
      STAT1alpha and STAT3. Interestingly, overlapping binding sites for STAT3 and NF
      kappaB can be found on promoters of several APP genes. We show here that both
      STAT3 and NF-kappaB are active during inflammation and are capable of binding to
      a STAT3/NF-kappaB overlapping DNA motif derived from the alpha2-macroglobulin
      gene promoter. In vitro binding assays demonstrated that NF-kappaB competes with
      STAT3 binding on this probe. Our results suggest that these transcription factors
      regulate each others' function through competition for overlapping DNA binding
      sites.

PMID- 9266836
TI  - Ceramide: a novel cell signaling mechanism for vasodilation.
AB  - Ceramide is a lipid second messenger generated by membrane hydrolysis of
      sphingomyelin by sphingomyelinase, but a role for this novel signaling pathway in
      vascular smooth muscle has not been elucidated. Based upon observations of
      cytokine-induced increases in sphingomyelinase activity, we hypothesized that
      ceramide plays a cell signaling role in vasodilation. Here, we demonstrate that
      ceramide is present at significant basal levels in cultured vascular smooth
      muscle cells and that these levels may be increased using exogenous
      sphingomyelinase. We also report that both exogenously added ceramide and
      sphingomyelinase cause dose-dependent relaxation in phenylephrine-contracted
      endothelium-denuded rat thoractic aortic rings. We conclude that the ceramide
      signaling pathway represents a novel signal transduction mechanism for
      vasodilation.

PMID- 9266837
TI  - Effect of enteral versus parenteral nutrition on leptin gene expression and
      release into the circulation.
AB  - Leptin, a putative satiety hormone in rodents, is acutely regulated by fasting
      and refeeding. To determine the role of satiety hormones that are secreted by the
      gastrointestinal tract on leptin regulation, leptin mRNA and serum concentrations
      were measured after feeding rats similar calories with standard chow or infusion
      of total parenteral nutrition into the duodenum or intravenously. We have
      demonstrated that leptin gene expression and hormone secretion into the
      circulation are stimulated equally in the three experimental paradigms; it is
      unlikely that satiety factors secreted by the intestinal tract play a significant
      role in leptin regulation. Furthermore, intravenous infusion of individual
      components of TPN demonstrated that intravenous glucose infusion was mostly
      responsible for stimulation of the leptin gene and hormone secretion.

PMID- 9266838
TI  - Calcium waves in unstimulated left ventricular cardiomyocytes isolated from aged
      spontaneously hypertensive and normotensive rats.
AB  - In this work, we described the incidence and the characteristics of calcium waves
      in cardiomyocytes isolated from aged normotensive rats (Wistar Kyoto, WKY) and
      age-matched spontaneously hypertensive rats (SHR) using imaging analysis of fura
      2-loaded left ventricular cardiomyocytes. Left ventricular cardiomyocytes were
      isolated by enzymatic digestion from hearts of 18-20 month old WKY and aged
      matched SHR. Intracellular calcium concentration did not differ in either strain,
      whereas the incidence of cells presenting calcium waves was greater in
      cardiomyocytes isolated from SHR. Moreover, cardiomyocytes isolated from SHR were
      significantly longer than those isolated from WKY. The calcium wave frequency was
      lower in SHR cardiomyocytes, while the velocity of the calcium waves was similar
      in both strains. Our results suggest that alterations in the calcium handling of
      SHR may contribute to the increased incidence of arrhythmias described in SHR
      hearts.

PMID- 9266839
TI  - Doxyclycline inhibits collagen synthesis by bovine chondrocytes cultured in
      alginate.
AB  - Doxycycline is known for its ability to inhibit matrix metalloproteinases (MMPs),
      a family of enzymes that play a role in cartilage breakdown in arthritides. Its
      prophylactic effect in reducing joint degradation in osteoarthritis is mainly
      attributed to this property. In this study, we show that doxycycline exhibits a
      profound inhibition of collagen synthesis by bovine articular chondrocytes
      cultured in alginate. At 25 microM doxycycline, collagen synthesis was decreased
      by 50%; no effect on cell proliferation (DNA levels) or general protein synthesis
      (35S-Met and 35S-Cys incorporation) was observed. Messenger RNA levels of type II
      collagen were also reduced, indicating an effect of doxycycline at the
      transcriptional level. The concentration of doxycycline needed to downregulate
      collagen synthesis was > 10-fold lower than that needed to inhibit most of the
      MMPs. Inasmuch as differentiated chondrocytes in the early stages of
      osteoarthritis exhibit increased collagen synthesis, the beneficial effect of
      doxycycline in vivo may involve prevention of changes in chondrocyte phenotype.

PMID- 9266840
TI  - Ca2+-ATPase inhibitors and Ca2+-ionophore induce osteoclast-like cell formation
      in the cocultures of mouse bone marrow cells and calvarial cells.
AB  - Osteoclasts which derive from hemopoietic cells are multinucleated cells
      responsible for bone resorption. We found that cyclopiazonic acid (CPA),
      thapsigargin (TG), and 2,5-di-(t-butyl)-1,4-hydroquinone (BHQ) induced osteoclast
      like cell (OCL) formation in cocultures of mouse calvaria-derived stromal cells
      and hemopoietic cells such as bone marrow cells and spleen cells. OCLs induced by
      these compounds showed typical characteristics of osteoclasts such as tartrate
      resistant acid phosphatase activity and pit forming activity. These compounds are
      known as endoplasmic reticulum (ER)/sarcoplasmic reticulum (SR) Ca2+-ATPase
      inhibitors that increase intracellular Ca2+ levels by inhibiting Ca2+-ATPase
      activity located in the membrane of ER/SR. Ca2+-ionophores such as ionomycin
      which increase intracellular Ca2+ levels also stimulated OCL formation in the
      cocultures. Differentiation of hemopoietic cells into OCLs induced by these
      compounds required the presence of calvarial cells. These results indicate that
      an increase of intracellular Ca2+ levels may be a part of signaling pathways to
      induce osteoclast differentiation in the presence of calvarial cells.

PMID- 9266841
TI  - Expression of a neutrophil chemotactic protein LECT2 in human hepatocytes
      revealed by immunochemical studies using polyclonal and monoclonal antibodies to
      a recombinant LECT2.
AB  - A recombinant human neutrophil chemotactic protein LECT2 (rhLECT2) was purified
      as a 16-kDa protein from the culture fluids of stable transfectants derived from
      CHO cells (clone C1D8-1) and L929 cells (clone L2E4-1). The N-terminal amino acid
      sequence of the protein secreted by both clones were homologous to the previously
      described bovine LECT2. We produced polyclonal and monoclonal antibodies against
      rhLECT2 and investigated secretion of LECT2 protein in six human hepatoma cell
      lines, which express LECT2 mRNA, and in hepatocytes of normal human livers by a
      sandwich enzyme-linked immunosorbent assay and by immunostaining using the
      antibodies, respectively. We revealed that five of six hepatoma cell lines
      secreted LECT2 into culture fluids at concentrations of 30-135 ng/mg. We also
      demonstrated that the cytoplasm of human hepatocytes was diffusely stained,
      although periportal hepatocytes tended to be weakly and granularly stained by
      immunostaining. These results indicated that the novel protein was expressed in
      hepatocytes and suggested an important role of LECT2 in the cells in addition to
      the activation of neutrophils.

PMID- 9266842
TI  - Restoration of defective mechanochemical properties of cleaved actins by native
      tropomyosin: involvement of the 40-50 loop in subdomain 2 of actin in interaction
      with myosin and tropomyosin.
AB  - Native tropomyosin activated sliding movement in vitro of F-actin with ATP by
      30%. Actin cleaved at the 40-50 loop by subtilisin or proteinase K slid on HMM
      much slower than intact actin, but native tropomyosin strikingly recovered this
      defective motility of cleaved actin by 2 to 3 times. On the other hand, with ATP
      analogues of CTP and ITP, sliding movements of cleaved actin and particularly
      intact actin were inhibited by native tropomyosin, indicating that native
      tropomyosin augmented specificity of the myosin substrate of NTP. These results
      suggested that the 40-50 loop in the small domain 2 of actin interacted directly
      or indirectly with tropomyosin and play a significant role in cross talk between
      myosin and native tropomyosin.

PMID- 9266843
TI  - Interleukin-18 induces activation and association of p56(lck) and MAPK in a
      murine TH1 clone.
AB  - Interleukin-18 (IL-18) was identified as an inducer of interferon-gamma (IFN
      gamma) production by stimulated T cells. In this study, we used an ovalbumin
      responsive murine Th1 clone (OVA#4), in which DNA synthesis was reportedly
      enhanced after IL-18 treatment in the presence of a non-mitogenic TCR/CD3
      stimulus, to examine signal transduction pathways. In the presence of the
      stimulus, IL-18 induced the appearance of tyrosine-phosphorylated proteins and
      herbimycin A inhibited DNA synthesis. It is suggested that protein tyrosine
      kinase (PTK) mediated signaling is induced by IL-18. Specifically, IL-18 induced
      phosphorylation of phosphorylates p56(lck) (LCK) and mitogen-activated protein
      kinase (MAPK). IL-18 alone induced the kinase activities of both LCK and MAPK,
      and the activities were increased by the TCR/CD3 stimulus. Simultaneously, IL-18
      induced the association of LCK with MAPK and this was also increased by the
      TCR/CD3 stimulus. The activation of the LCK-MAPK pathway correlated with enhanced
      DNA synthesis in OVA#4 cells. These results suggest that the LCK-MAPK pathway is
      involved in IL-18 signaling and that IL-18 may play an important role in
      modification of TCR/CD3-mediated response.

PMID- 9266844
TI  - Distinct substrate specificities of five human alpha-1,3-fucosyltransferases for
      in vivo synthesis of the sialyl Lewis x and Lewis x epitopes.
AB  - Five different human alpha-1,3-fucosyltransferase genes, the Fuc-TIII, Fuc-TIV,
      Fuc-TV, Fuc-TVI and Fuc-TVII genes, have been cloned to date. We transfected HeLa
      cells and Namalwa cells with each of the five different genes, and established a
      series of stable cloned transformant cells. Thin-layer chromatography
      immunostaining analysis revealed that all five enzymes were able to synthesize
      sialyl Lewis x (sLe(x)) epitopes on glycolipids in HeLa cells, but each enzyme
      showed a different preference as to the carbohydrate chain length on glycolipids
      as acceptor substrates. Fuc-TIII and Fuc-TV showed very similar patterns of
      sLe(x) positive bands, which indicated that the enzymes have similar acceptor
      substrate specificities. Fuc-TVI exhibited a little different pattern from those
      of the former two enzymes. Fuc-TIV and Fuc-TVII showed similarity in the positive
      bands, however, their patterns were quite different from those of the former
      three enzymes. Four enzymes except for Fuc-TVII were able to synthesize the Lewis
      x (Le(x)) epitope on glycolipids in HeLa cells. Fuc-TV alone showed a little
      different pattern of Le(x) positive bands from those of the other three enzymes.
      Flow cytometric analysis of HeLa cells and Namalwa cells again demonstrated the
      similar specificities of Fuc-TIII and Fuc-TV. They exhibited similar stronger
      staining with FH6 (anti-sLe(x)) antibodies than that with the other enzymes. A
      phylogenetic tree of the five enzymes constructed using the neighbor-joining
      method showed good agreement with the similarities in the enzyme substrate
      specificity.

PMID- 9266845
TI  - Evidence for the presence of the second allele of the neurofibromatosis type 1
      gene in melanocytes derived from cafe au laitmacules of NF1 patients.
AB  - Neurofibromatosis type 1 (NF1) is an autosomal dominantly inherited disorder
      caused by mutations in the NF1 gene on 17q11.2. Melanocytes cultured from cafe au
      lait macules (CALM) of patients with NF1 were analysed for loss of heterozygosity
      (LOH) at the NF1 locus using a 3'-flanking and four intragenic markers. None of
      the informative samples showed LOH. In addition, the X-inactivation pattern of
      melanocytes from CALM (n = 4) and from the unaffected skin of the patients (n =
      3) suggests a monoclonal origin of the cells isolated from skin biopsies up to 2
      cm2 in size.

PMID- 9266846
TI  - Linoleic acid metabolism in primary cultures of adult rat cardiomyocytes is
      impaired by aging.
AB  - Many of the changes that occur in the rat cardiac muscle with advancing age are
      related to modifications in membrane fatty acid composition, polyunsaturated
      fatty acids decreasing and saturated increasing as the animal develops. In the
      present study, using cultured adult cardiomyocytes isolated from the hearts of
      rats of a broad (1-24 months) age range, we demonstrated that the modifications
      in the fatty acid pattern of cardiomyocytes have to be related to alterations in
      the mechanism of desaturation/elongation of essential fatty acids. In fact,
      independent of the age of the animal, heart cells in culture were capable of
      rapidly metabolizing radiolabeled linoleic acid taken up from the surrounding
      medium, but to a different extent. The ability of heart cells to metabolize
      linoleic acid to higher and more unsaturated metabolites decreased with the
      animal's age. As the age of the animal increased, the pattern of fatty acids of
      the cultured cardiomyocytes showed a gradual but significant shift, similar to
      those reported in the whole heart. Data here reported confirm that the basic
      aging-related process in the cellular model system may also be relevant to aging
      in the whole animal.

PMID- 9266847
TI  - PAF-induced eosinophil chemotaxis increases during an asthmatic attack and is
      inhibited by prednisolone in vivo and in vitro.
AB  - We investigated platelet-activating factor (PAF)-induced migration in eosinophils
      obtained from asthmatic patients who were treated with or without intravenous
      prednisolone. The migration of asthmatic eosinophils in remission and during an
      attack was significantly greater than that in healthy volunteers. The migration
      of asthmatic eosinophils exposed to prednisolone in vivo and in vitro was
      significantly inhibited, compared to asthmatic eosinophils not exposed to
      prednisolone. These findings suggest that an intracellular factor causes
      asthmatic eosinophils to migrate, and that prednisolone inhibits PAF-induced
      eosinophil migration.

PMID- 9266848
TI  - Primary structure of human PMP69, a putative peroxisomal ABC-transporter.
AB  - We have cloned the cDNA of a novel human ABC-half-transporter highly similar to
      peroxisomal ABC-half-transporters such as the adrenoleukodystrophy protein (ALDP)
      and the peroxisomal protein 70 (PMP70). This 2927-bp cDNA codes for a 606
      aminoacid (68.6 kDa) protein that was designated PMP69 (putative peroxisomal
      membrane protein). PMP69 is ubiquitously expressed. Transcript variants resulting
      from alternative polyadenylation and splicing events including one that confers
      an alternative C-terminus have been found. The PMP69 gene is localized on
      chromosome 14q24.3. ABC-half-transporters require a partner ABC-half-transporter
      to constitute a functional complex, either as a homodimer or a heterodimer.
      Defects in the gene coding for ALDP are the cause of adrenoleukodystrophy, a
      demyelinating disorder of the nervous system with strikingly varying clinical
      courses. PMP70 was implicated in the pathogenesis of a subgroup of Zellweger
      syndrome, a heterogenous group of peroxisome assembly disorders. PMP69 might be a
      heterodimer partner for one of these proteins, thus playing a role in modifying
      the clinical course of ALD or, alternatively, in peroxisome biogenesis.

PMID- 9266849
TI  - ATF-like element contributes to hepatic activation of human angiotensinogen
      promoter.
AB  - Angiotensinogen is the precursor protein of angiotensin II that is involved in
      regulating blood pressure and electrolyte homeostasis, and it is mainly
      synthesized in the liver. In the present study, we analyzed the human
      angiotensinogen proximal promoter region by means of Chloramphenicol
      acetyltransferase assays, and suggested that the region from -106 to +44 is
      sufficient for hepatoma cell line (HepG2)-specific expression. Electrophoretic
      mobility shift assays using ALE (ATF-like element, -102 to -87) fragment
      identified CREB/ATF family nuclear factors and novel ones, ALF (ALE-binding
      factor). The deletion and in vivo competition of ALE decreased the human
      angiotensinogen promoter activity. Furthermore, the heterologous promoter
      analysis demonstrated that ALE acts as a HepG2-dependent activating element.
      These results indicate that ALE plays an important role in hepatic expression of
      human angiotensinogen gene.

PMID- 9266850
TI  - Protein half-lives of calmodulin and the plasma membrane Ca-ATPase in rat brain.
AB  - We report the half-lives for two proteins involved in the regulation of
      intracellular calcium in the brain: the plasma membrane Ca-ATPase and its
      regulatory protein, calmodulin. [14C]-labeled leucine was injected into seven
      month old adult Fischer 344 rats and the time-dependent appearance and loss of
      radioactivity was monitored in both the serum and proteins from the brains of
      rats sacrificed from 4 hours to 13 days after injection. Experimental data
      obtained for calmodulin and the plasma membrane Ca-ATPase are best described by
      theoretical curves accounting for leucine reutilization that assume apparent half
      lives of 18 (+/-2) hours and 12 (+/-1) days, respectively.

PMID- 9266851
TI  - ACV synthetase: expression of amino acid activating domains of the Penicillium
      chrysogenum enzyme in Aspergillus nidulans.
AB  - Fragments of ACV synthetase of Penicillium chrysogenum carrying partial
      activities of amino acid activation were expressed under the alcA promoter in an
      acvA-deletion mutant of Aspergillus nidulans. The 210 kDa domain A-beta
      galactosidase fusion protein was partially cleaved to fragments of 200 and 97
      kDa. The domain A fragment and the 312 kDa domain BC construct were identified by
      peptide specific antibodies and shown to catalyze alpha-aminoadipate-, cysteine-,
      and valine-dependent ATP/[32P]PPi exchange activity. Substrate specificities were
      investigated using amino acid analogues. Unexpectedly neither alpha-aminoadipate
      nor valine activation was exclusive, implying possible misactivations and proof
      reading functions. Both fragments were only expressed in limited amounts and
      found to be unstable.

PMID- 9266852
TI  - Distal regulatory regions of the rat MRF4 gene.
AB  - MRF4 is a muscle-specific transcription factor that is expressed both in
      embryonic somites and later in fetal and adult muscle fibers. Cis-regulatory
      elements of the MRF4 gene responsible for its complex expression pattern have not
      yet been identified, although previous studies of the rat MRF4 gene have
      demonstrated the presence of enhancer activity located several kilobases 5' to
      the transcription start site. Using cell transfection assays in vitro, we have
      now localized one of the regulatory regions of MRF4 to a 590-base-pair sequence
      between 4 and 5 kilobases upstream from the start site. This sequence region
      functioned as an enhancer in combination either with the MRF4 promoter or with
      the viral thymidine kinase (tk) promoter. Deletion analysis of MRF4 indicated the
      existence of another regulatory region, closer to the promoter, which functioned
      as an enhancer in combination with the MRF4 promoter but not with the tk
      promoter.

PMID- 9266853
TI  - Molecular cloning of an alternative human alphaE-catenin cDNA.
AB  - The cytoplasmic protein alpha-catenin plays a crucial role in E-cadherin mediated
      cell-cell adhesion by binding E-cadherin to the cytoskeleton via beta- or gamma
      catenin and actin. Functional loss of one of these interacting components leads
      to decreased cell-cell adhesion, and therefore to loss of epithelial integrity.
      Northern analysis revealed two distinct alphaE-catenin transcripts in different
      cell lines, whereas apparently only one protein is expressed. Because of the
      biological importance of this protein we sought to molecularly characterize the
      differences between the two observed transcripts. cDNA cloning and sequence
      analysis revealed the earlier described 3.4 kb alphaE-catenin transcript and an
      alphaE-catenin transcript of approximately 3.8 kb. This larger transcript
      contains a 321 bp extension in the 3'UTR sequence, which probably arises as a
      result of alternative polyadenylation. Considering the presence of AU-rich
      sequences in the extension, it may be involved in mRNA stability.

PMID- 9266854
TI  - The D1-A2 and D2-A2 pairs of splice sites from human immunodeficiency virus type
      1 are highly efficient in vitro, in spite of an unusual branch site.
AB  - Using in vitro splicing assays with HeLa cell nuclear extracts, we showed that
      the HIV-1 pairs of splice sites D1-A2 and D2-A2 are efficiently used in vitro, as
      compared to the control D1-A2 pair of sites from the E3 transcription unit of
      human adenovirus-2. The strong efficiency of the two HIV-1 pairs of sites is
      surprising, as we also showed by primer extension analysis that the branch-site
      sequence used at the HIV-1 acceptor site A2 is UAGCAGA, with a dominant
      utilization of the ultimate G as the branched residue. No significant increase of
      the splicing efficiency was observed upon replacement of the wild-type branch
      site sequence by a canonical sequence, in spite of the utilization of an A
      residue as the branched nucleotide. Results are discussed taking into account the
      present knowledge on branch-site selection.

PMID- 9266855
TI  - Isolation, chemical characterization, and quantitation of A beta 3-pyroglutamyl
      peptide from neuritic plaques and vascular amyloid deposits.
AB  - From the neuritic plaques and vascular walls of the brains of patients with
      Alzheimer disease, we have purified and quantified an A beta peptide which starts
      at residue 3Glu in the form of pyroglutamyl (A beta3pE). The N-terminally
      truncated A beta3pE comprised 51% of the A beta in the neuritic plaques. This was
      followed by 30% starting at position 1Asp which included 20% in the isomerized
      form (IsoAsp). In contrast, the vascular amyloid only contained an average of 11%
      in the form of A beta3pE with the major component starting at residue 1Asp (69%),
      which included only 6% in the form of IsoAsp. The presence of A beta3pE has
      important structural consequences since it is more hydrophobic than other forms
      of A beta, thus increasing the insolubility of A beta. In addition, A beta3pE,
      with its blocked N-terminus to the action of common aminopeptidases, may result
      in the profuse accumulation of A beta in the neuritic plaques of Alzheimer
      disease.

PMID- 9266856
TI  - Isolation and analysis of mutated histidyl-tRNA synthetases from Escherichia
      coli.
AB  - Amino terminally deleted and point-mutated histidyl-tRNA synthetases were
      purified from E. coli via betaGal fusion proteins. A hinge region proximal and
      distal to the factor Xa cleavage region was necessary to cut the betaGal-fusion
      proteins efficiently under very mild nondenaturing conditions. N-terminal
      addition of either methionine or valine to this enzyme (its starting N-formyl
      methionine is in vivo post-translationally removed) or the deletion of 6 amino
      terminal amino acids decreased the specific aminoacylation activity 2- to 7-fold.
      Further N-terminal deletions of 10 or 17 amino acids caused significantly reduced
      aminoacylation (100-fold) and ATP/PPi exchange (10-fold) activities, and a
      reduced binding affinity for histidine. Removal of 18 or more amino acids from
      the N-terminus thereby removing residues from MOTIF 1 resulted in inactive
      histidyl-tRNA synthetase mutants. Two point mutations within the histidyl
      adenylate binding pocket, R259Q and R259K, also blocked histidyl-tRNA synthetase
      activity without affecting histidine or ATP binding. The experiments shown
      identify a highly conserved N-terminal R/KG-patch in front of MOTIF 1 as well as
      R259 as vital for full enzymatic activity.

PMID- 9266857
TI  - Is coronary artery disease an infectious disease?

PMID- 9266858
TI  - Aerosols for the intubated: cultivating the rose.

PMID- 9266859
TI  - Effects of selective digestive decontamination on lung injury and outcome: the
      verdict is not yet in.

PMID- 9266860
TI  - What's the rush? Trust the process.

PMID- 9266861
TI  - Mr. Jack Emerson--a matter of life and breath.

PMID- 9266862
TI  - A possible association of Chlamydia pneumoniae infection and acute myocardial
      infarction in patients younger than 65 years of age.
AB  - STUDY OBJECTIVES: We conducted a retrospective study on patients with acute
      myocardial infarction (AMI) and evaluated the incidence and prevalence of
      Chlamydia pneumoniae infection. METHODS: Sixty-one consecutive patients with AMI
      aged younger than 65 years were enrolled. Within 24 h of hospital admission,
      serum samples and pharyngeal swab specimens were obtained from all patients. In
      49 of 61 patients, after a mean of 28 days from hospital admission, a second
      serum sample was drawn. A third serum sample was obtained in 23 of 61 patients.
      Serologic testing for Chlamydia pneumoniae was performed by a
      microimmunofluorescence test. We applied a nested-polymerase chain reaction for C
      pneumoniae DNA detection to pharyngeal swab specimens. Simultaneously, we
      performed a serologic study for C pneumoniae infection on 61 serum samples
      obtained from blood donors, matched for age, sex, and smoking habits. RESULTS:
      Serologic test results for C pneumoniae were consistent with acute reinfection in
      12 patients, with chronic infection in 23 patients, and results were negative in
      26 patients with AMI. In 3 of 12 patients with acute reinfection pattern and in 3
      of 23 patients with chronic infection pattern, C pneumoniae DNA was detected on
      pharyngeal swab specimens. A significantly higher prevalence of IgG titers was
      observed in patients with AMI (35/61) compared to blood donors (18/61) (p=0.003).
      CONCLUSION: Our data confirm the possible role of C pneumoniae infection in
      coronary heart disease and suggest that reinfection may trigger the onset of AMI.

PMID- 9266863
TI  - Smoking cessation is associated with an increase in exhaled nitric oxide.
AB  - STUDY OBJECTIVES: Nitric oxide (NO), a gas produced by cells lining the
      respiratory tract, has been reported to be decreased in the exhaled air of
      cigarette smokers. We hypothesized that smoking cessation would result in an
      increase in exhaled NO. DESIGN: Comparison of exhaled NO measured from
      nonsmokers, cigarette smokers, and smokers after smoking cessation. SETTING:
      University outpatient smoking cessation clinic. PATIENTS OR PARTICIPANTS: Twenty
      five cigarette smokers and 23 normal, nonsmokers. INTERVENTIONS: Exhaled NO was
      measured by three techniques: (1) a peak oral method; (2) a mean oral method; and
      (3) a nasal method. The smokers were given nicotine patches and instructed to
      return after 1 and 8 weeks. The exhaled NO determinations were repeated on each
      visit. MEASUREMENTS AND RESULTS: Compared with nonsmokers, smokers had decreased
      NO levels measured by all three methods (p<0.05, each comparison). Nineteen
      smokers returned after 1 week. Fourteen were successfully abstinent from
      cigarettes and their exhaled NO increased compared with baseline (p<0.01 for each
      method) but not in the five subjects who had not successfully quit smoking
      (p>0.05 for each method). Ten subjects returned after 8 weeks. The exhaled NO
      levels increased further and were not significantly different from the normal
      nonsmokers for the peak oral and nasal NO methods (p>0.2), but were still lower
      than the normal nonsmoker mean oral NO (p=0.018). CONCLUSIONS: These data
      demonstrate that smoking cessation is associated with an increase in exhaled NO.

PMID- 9266864
TI  - Tracheobronchial histopathology in habitual smokers of cocaine, marijuana, and/or
      tobacco.
AB  - BACKGROUND: Marijuana and alkaloidal cocaine ("crack") are the two most commonly
      smoked substances in the United States after tobacco. While regular tobacco
      smoking has been found to be associated with extensive microscopic alterations in
      bronchial mucosa, little information is available concerning the effect of crack
      cocaine and marijuana on tracheobronchial histopathology. STUDY OBJECTIVE: To
      determine the relative impact of smoked substances (cocaine, marijuana, and
      tobacco) alone and in combination on the histopathology of the tracheobronchial
      mucosa and to assess whether the effects of habitual smoking of two or more
      substances (cocaine, marijuana, and/or tobacco) are additive. DESIGN:
      Observational cohort study. SUBJECTS: Fifty-three nonsmoking control subjects
      (NS), 14 current, habitual smokers of crack cocaine only (CS), 40 current,
      regular smokers of marijuana only (MS), 31 regular smokers of tobacco only (TS),
      16 current smokers of both cocaine and marijuana (CMS), 12 current smokers of
      both cocaine and tobacco (CTS), 44 current smokers of both marijuana and tobacco
      (MTS), and 31 current smokers of cocaine, marijuana, and tobacco (CMTS). METHODS:
      After preliminary screening evaluation, including a detailed respiratory and
      general health questionnaire and routine pulmonary function studies, subjects
      underwent fiberoptic bronchoscopy with endobronchial biopsies of the mucosa of
      the primary carina and randomly selected secondary or tertiary carinae. Biopsy
      specimens were processed for light microscopy, stained with hematoxylin-eosin or
      periodic acid-Schiff, and examined to assess epithelial, basement membrane, and
      submucosal alterations by one or two pathologists who were masked to the smoking
      status of the subject. RESULTS: Smokers of cocaine, marijuana, or tobacco alone
      all exhibited more frequent abnormalities than NS in 10 (CS) or all 11 (MS and
      TS) of the histopathologic features assessed. For most features, MS and TS showed
      significantly more frequent alterations than NS (p < or = 0.02), while CS showed
      significantly more frequent abnormalities than NS in only three features (p<0.05)
      and nearly significant differences from NS in two additional features (p < or =
      0.09). Alterations were noted most frequently in CTS (six features) and MTS
      (three features), while abnormalities were relatively infrequent in CMS. For 10
      features, MTS had more frequent alterations than MS and TS. With a single
      exception, CMTS did not show more frequent alterations than CTS or MTS.
      CONCLUSION: Marijuana and tobacco smoking each produces significant bronchial
      mucosal histopathology and the effects of marijuana and tobacco appear additive.
      Cocaine appears to lead to fewer significant bronchial mucosal alterations than
      marijuana or tobacco when smoked alone and does not add to the changes associated
      with marijuana. When smoked together with tobacco, however, cocaine appears to
      augment the bronchial injury caused by tobacco smoking.

PMID- 9266865
TI  - Effects of 'crack' cocaine on pulmonary alveolar permeability.
AB  - BACKGROUND: Lung clearance of 99mTc-labeled diethylenetriamine pentaacetate
      (DTPA) is a sensitive test of altered alveolar epithelial permeability that has
      been found to be increased in smokers of tobacco, as well as a small number of
      healthy smokers of crack cocaine, suggesting the possibility of subclinical crack
      related lung injury. STUDY OBJECTIVE: To evaluate further whether habitual
      smoking of cocaine alone alters alveolar permeability, whether crack smoking adds
      to or potentiates the effects of tobacco and/or marijuana, and whether
      experimental cocaine smoking acutely alters DTPA lung clearance. DESIGN:
      Observational cohort study (habitual cocaine smoking) and single-blind crossover
      study (experimental cocaine administration). SUBJECTS: Fourteen habitual smokers
      of cocaine alone (CS), 19 smokers of cocaine and tobacco (CTS), 3 smokers of
      cocaine and marijuana, 12 smokers of cocaine, tobacco, and marijuana (CMTS), and
      5 smokers of marijuana plus tobacco (MTS). Results obtained in the crack-smoking
      subjects were compared with data previously obtained in 10 nonsmokers (NS), 9
      smokers of tobacco alone (TS), 10 smokers of marijuana alone (MS), and 4
      additional MTS. METHODS: Subjects underwent measurements of DTPA radioaerosol
      lung clearance after refraining from marijuana and/or cocaine for > 12 h and from
      tobacco for >2 h. Ten of the 48 crack users were tested on two days 1 to 2 weeks
      apart within 2 h of experimental smoking of three physiologically active or
      inactive doses (total 98.8+/-15.5 or 8.5+/-2.5 mg, respectively) of cocaine base.
      Lung clearance half-times (T1/2) were computed from time-activity curves for each
      lung. RESULTS: T1/2 values for each lung in CS and MS were comparable to those of
      NS, while TS, MTS, CTS, and CMTS had significantly shorter clearance rates than
      NS (p<0.01; three-way analysis of variance). No additive or interactive effects
      on T1/2 were noted among tobacco, cocaine, and/or marijuana. No acute effect of
      experimental cocaine smoking on T1/2 was noted. CONCLUSION: Whereas regular
      smoking of tobacco alone or with other substances increases alveolar epithelial
      permeability, habitual smoking of cocaine and/or marijuana has no measurable
      effect on alveolar permeability in the absence of tobacco nor any additive effect
      to that of tobacco alone.

PMID- 9266866
TI  - Salmeterol reduces dyspnea and improves lung function in patients with COPD.
AB  - STUDY OBJECTIVE: To investigate the short-term effects of inhaled salmeterol on
      the perception of dyspnea and lung function in patients with COPD. DESIGN: Double
      blind, crossover, randomized trial comparing inhaled salmeterol and inhaled
      placebo over 4 h. SETTING: Pulmonary function laboratory at university medical
      center. PATIENTS: Sixteen patients with symptomatic COPD and at least 200-mL
      increase in FEV1 after inhalation of two puffs (180 microg) of albuterol.
      INTERVENTIONS: Visit 1 was used for familiarization. At visits 2 and 3 (2 to 3
      days apart), patients inhaled either two puffs of salmeterol (42 microg) or
      placebo. MEASUREMENTS AND RESULTS: Lung function and dyspnea were measured at
      0.5, 2, and 4 h after inhalation of the study medication. Dyspnea was measured by
      the -5 to +5 category scale at rest and by the 0 to 10 category-ratio scale while
      breathing through inspiratory resistances of 5, 15, and 30 cm H20/L/s. Age was
      66+/-8 years (mean+/-SD). FEV1 was 0.97+/-0.331 (51+/-13% predicted). There were
      significantly higher values for FEV1 and FVC (at all time periods) and lower
      values for functional residual capacity (at all time periods) and residual volume
      (at 4 h) with salmeterol than with placebo. There were significantly lower
      dyspnea ratings on the -5 to +5 category scale (p=0.03 at 2 h and p=0.02 at 4 h)
      and for the mean dyspnea scores during resistive breathing with salmeterol
      compared with placebo (p=0.002). CONCLUSIONS: Inhaled salmeterol reduced dyspnea,
      increased airflow, and reduced hyperinflation over 4 h in patients with
      symptomatic COPD.

PMID- 9266867
TI  - Decreased C4 complement component serum levels correlate with the degree of
      emphysema in patients with chronic bronchitis.
AB  - Patients with COPD who fulfill the diagnostic criteria of chronic bronchitis have
      been shown to exhibit lower serum levels of complement components C3 and C4 than
      healthy subjects, and this may indicate sustained complement activation as a
      result of recurrent respiratory tract infections. Since activation of complement
      leads to influx of inflammatory cells into the lung parenchyma with subsequent
      release of elastases and oxidants that cause damage to elastic lung tissue, we
      postulated that there might be a quantitative relationship between complement
      consumption and degree of elastic tissue destruction. In this study, we tried to
      investigate possible correlations between serum levels of C3 and C4 and degree of
      emphysema among patients with COPD of the bronchitic type. We studied 20 patients
      with chronic bronchitis aged 68+/-1 years (mean+/-SEM) without significant
      fluctuations of serum C3 and C4 levels over a 3-month period by performing
      detailed lung function tests, recording of emphysema score in chest radiogram,
      and the incidence of infective exacerbations during the past 3 years. Measured C3
      and C4 serum levels were 124+/-9 and 28.5+/-2 mg/dL, respectively, lower than the
      respective levels in control subjects (141+/-3 and 39+/-2 mg/dL, respectively).
      Significant correlations were observed between levels of C4 and (1) incidence of
      respiratory tract infections during the past 3 years (r=-0.747, p<0.001), (2)
      radiologic emphysema score (r=-0.936, p<0.001), and (3) various functional
      indexes, such as midexpiratory flow rate, percent of predicted (r=0.629, p<0.01),
      forced expiratory flow rate at 50% of vital capacity, percent of predicted
      (r=0.606, p<0.01), residual volume/total lung capacity ratio (r=-0.651, p<0.01),
      and the exponential constant of static pressure-volume curve (r=-0.606, p<0.01).
      These results suggest that patients with chronic bronchitis with the lowest
      levels of C4 are those experiencing more frequent respiratory infections, tend to
      have more signs indicative of emphysema in their chest radiograph, have a more
      prominent small airways dysfunction and gas trapping, and present a greater
      defect in lung elastic recoil.

PMID- 9266868
TI  - Emergency treatment of acute asthma with albuterol metered-dose inhaler plus
      holding chamber: how often should treatments be administered?
AB  - STUDY OBJECTIVE: To determine the optimal treatment interval for administering
      albuterol metered-dose inhaler (MDI) with a holding chamber to patients
      presenting to the emergency department (ED) with acute asthma. DESIGN:
      Prospective, randomized, double-blind study. SETTING: EDs of two affiliated
      teaching hospitals in the Bronx, NY. PATIENTS: One hundred adult patients with
      acute asthma and FEV1 <60% predicted of normal. INTERVENTIONS: At entry (T=0
      min), eligible patients all openly received inhaled albuterol (six puffs) via MDI
      with a spacer. Subsequently, in a double-blind fashion, they received six puffs
      of albuterol or placebo with new MDIs and spacers at 30, 60, and 90 min such that
      group 1 (n=34) received albuterol every 30 min, group 2 (n=33) every 60 min, and
      group 3 (n=33) at 120 min only. FEV1 and vital signs were measured at T=0 and at
      15, 30, 60, 90, and 120 min following initial treatment. Potassium levels were
      measured at T=0 and 120 min. Adverse events, the use of additional inhaled beta
      agonists or systemic corticosteroids, and hospitalization rates were recorded.
      MEASUREMENTS AND RESULTS: At T=0, the groups did not differ in age, FEV1, or
      prescribed asthma medications. All groups showed significant improvement in FEV1
      (p<0.05; T=120 vs 0 min). The conditions of groups 1 and 2 improved significantly
      more than those of group 3, but did not differ compared to each other. The mean+/
      SEM change in FEV1 (T=120 vs 0 min) was 0.993+/-0.108, 0.858+/-0.135, and 0.321+/
      0.056 L, respectively, for the three groups. Separate analysis for patients with
      FEV1% <40% or >40% predicted showed similar results. However, patients who
      initially were low responders to albuterol treatment (<15 percentage point
      increase at 15 min) improved significantly with 30-min treatments compared to the
      other two treatment regimens. Patients who initially responded with >15
      percentage point increase in FEV1 at 15 min following initial albuterol
      inhalation benefited equally from 30- or 60-min treatments compared to 120 min.
      Potassium levels did not change significantly during the study. Adverse events
      and hospitalization rates were equivalent. After the conclusion of the study,
      group 3 patients required a greater number of beta-agonist treatments prior to
      eventual discharge from the ED. CONCLUSIONS: For acute asthma, albuterol MDI with
      a holding chamber can be given optimally at 60-min intervals with minimal adverse
      effects for the majority of patients. However, patients who initially demonstrate
      a low or poor bronchodilator response to albuterol should be given subsequent
      treatments at 30-min intervals. This will optimize care and conserve resources
      for patients who will benefit the most.

PMID- 9266869
TI  - Distribution of disease in cystic fibrosis: correlation with pulmonary function.
AB  - STUDY OBJECTIVE: We hypothesized that the radiographic distribution of disease is
      important in determining pulmonary function, with the lower lung zones of more
      importance than the upper lung zones. To test this hypothesis, we retrospectively
      studied patients with cystic fibrosis, a disease with a known proclivity for the
      upper lung zones. SUBJECTS AND METHODS: Two hundred seventy-six chest radiographs
      obtained at 2- to 3-year intervals from 51 patients were scored by two
      radiologists using a 100-point visual severity scale. The distribution of disease
      was assessed by dividing the lungs into four equal horizontal zones and scoring
      each zone for the severity of disease. There were 146 concurrent chest
      radiographs and pulmonary function tests from which multiple linear regression
      was used to correlate these zonal scores with FEV1/FVC percent predicted.
      RESULTS: There was excellent interobserver agreement, intraclass correlation
      coefficients >0.7. The distribution of disease became predominant in the upper
      lung zones as the patients aged. Although the median score in the upper lung
      zones was nearly twice that of the lower lung zones, the lower lung zones were
      nearly three times (partial F ratio; 6.9 lower zone score vs 2.4 upper lung zone
      score) as important in determining pulmonary function. CONCLUSION: The regional
      distribution of disease is important in determining pulmonary function. Sparing
      of the lower lung zones is important in preserving pulmonary function.

PMID- 9266870
TI  - Long-term outcome of pulmonary rehabilitation in patients with COPD.
AB  - BACKGROUND: This study investigates the long-term benefits of pulmonary
      rehabilitation in terms of health-related quality of life (HRQL). Such
      information is of particular importance in developing strategies for aftercare at
      home which aim to maintain the initial improvements seen after rehabilitation.
      METHODS: Criteria for inclusion were diagnosis of COPD, age 40 to 80 years, and
      completion of an inpatient pulmonary rehabilitation program. HRQL was assessed by
      the St. George Respiratory Questionnaire, and the component "well-being" from the
      Medical Psychological Questionnaire for Lung Diseases. Patient characteristics
      included lung function parameters such as FEV1, the diffusion capacity for carbon
      monoxide and maximal inspiratory mouth pressure, age, socio-economic variables,
      and exercise tolerance evaluated by a 12-min walking test. To define patients in
      whom long-term benefits were sustained 9 months postdischarge, cases were
      clustered using hierarchical cluster analysis, based on the HRQL scores at
      discharge. RESULTS: Complete data sets were obtained from 77 patients. Two groups
      of cases were clustered. Patient characteristics were essentially the same in
      both groups. HRQL differed significantly between groups on admission, at
      discharge, and at follow-up. Within-group analysis revealed that patients in
      group 1 (n=44) had "moderate" scores on HRQL on admission, a significant
      improvement between admission and discharge, followed by a significant
      deterioration of HRQL at follow-up. Group 2 (n=33) had "severely" impaired HRQL
      on admission, little improvement after rehabilitation, and remained in fairly
      stable condition 9 months postdischarge. CONCLUSIONS: Results suggest that
      patients with COPD require a differentiated aftercare program of postdischarge
      pulmonary rehabilitation.

PMID- 9266871
TI  - Economic analysis of respiratory rehabilitation.
AB  - STUDY OBJECTIVE: We report on the incremental costs associated with improvements
      in health-related quality of life (HRQL) following 6 months of respiratory
      rehabilitation compared with conventional community care. DESIGN: Prospective
      randomized controlled trial of rehabilitation. SETTING: A respiratory
      rehabilitation unit. PARTICIPANTS: Eighty-four subjects who completed the
      rehabilitation trial. INTERVENTION: Two months of inpatient rehabilitation
      followed by 4 months of outpatient supervision. MEASUREMENTS AND RESULTS: All
      costs (hospitalization, medical care, medications, home care, assistive devices,
      transportation) were included. Simultaneous allocation was used to determine
      capital and direct and indirect hospitalization costs. The incremental cost of
      achieving improvements beyond the minimal clinically important difference in
      dyspnea, emotional function, and mastery was $11,597 (Canadian). More than 90% of
      this cost was attributable to the inpatient phase of the program. Of the
      nonphysician health-care professionals, nursing was identified as the largest
      cost center, followed by physical therapy and occupational therapy. The number of
      subjects needed to be treated (NNT) to improve one subject was 4.1 for dyspnea,
      4.4 for fatigue, 3.3 for emotion, and 2.5 for mastery. CONCLUSION: Cost estimates
      of various approaches to rehabilitation should be combined with valid, reliable,
      and responsive measures of outcome to enable cost-effectiveness measures to be
      reported. Comparison studies with the same method are necessary to determine
      whether the improvements in HRQL that follow inpatient rehabilitation are cheap
      or expensive. Such information will be important in identifying the extent to
      which alternative approaches to rehabilitation can influence resource allocation.
      A consideration of cost-effectiveness from the perspective of NNT may be useful
      in the evaluation of health-care programs.

PMID- 9266872
TI  - Home oxygen therapy in Medicare beneficiaries, 1991 and 1992.
AB  - STUDY OBJECTIVE: Obtain descriptive data on the use of home oxygen by Medicare
      beneficiaries and study the impact of certain demographic factors and diagnoses
      on oxygen use. METHODS: A home oxygen user was defined as any Medicare
      beneficiary with at least one claim for home oxygen in the Health Care Financing
      Administration National Claims History 5% Physician Supplier Files for 1991 and
      1992. Railroad board beneficiaries, health maintenance organization members, and
      those without continuous part B coverage were excluded. RESULTS: In 1991, there
      were 21,489 beneficiaries in the sample who received oxygen therapy. In 1992,
      there were 8,418 new users. Twenty-six percent of new users died in 1992. Factors
      significantly associated with death included age 76 years or older (relative risk
      [RR], 1.3), pneumonia (RR, 1.3), lung cancer (RR, 3.8), male gender (RR, 1.2),
      heart failure (RR, 1.3), and diagnoses suggestive of COPD (RR, 0.45). Seven
      percent of new users discontinued therapy within 1 month, 28% within 6 months.
      Liquid oxygen was used by 19% of current and 14% of new users. Factors
      significantly associated with liquid oxygen use included portable oxygen claims
      (odds ratio [OR], 2.4), nonmetropolitan residence (OR, 0.73), and white race (OR,
      1.2). CONCLUSIONS: Descriptive information on patterns of home oxygen use,
      including associated medical conditions, types and duration of therapy, and
      survival is useful for regulatory purposes. This information supports concerns
      that current payment policy may discourage suppliers from providing liquid oxygen
      in underserved areas.

PMID- 9266873
TI  - DNA fingerprints from Mycobacterium tuberculosis isolates of patients confined
      for therapy noncompliance show frequent clustering.
AB  - STUDY OBJECTIVE: To test the hypothesis that individuals chronically noncompliant
      with antituberculous chemotherapy are vectors for ongoing transmission of the
      disease in the community. DESIGN: Cohort study. SETTING: A large public hospital
      with a tuberculosis detention unit for patients with repeated and prolonged
      nonadherence to therapy. PATIENTS: Mycobacterium tuberculosis isolates from
      patients confined on the detention unit were obtained from the hospital's
      mycobacteriology laboratory. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: A
      standardized IS6110-based Southern blot hybridization protocol was used to
      genotype M tuberculosis isolates recovered from patients confined on the
      detention unit at the hospital. Each DNA fingerprint pattern was compared with
      the IS6110-fingerprint database at the Public Health Research Institute
      Tuberculosis Center, which has archived fingerprint patterns from over 2,500 M
      tuberculosis isolates collected from New York City patients in the past 5 years.
      Eighty percent of available isolates from detained patients belonged to an
      identifiable DNA fingerprint cluster, suggesting an epidemiologic link between
      the detainees and other New York City tuberculosis patients. CONCLUSIONS: Chronic
      noncompliance with therapy is associated with ongoing spread of tuberculosis in
      the community. Aggressive measures, including detention, for the small number of
      recalcitrant, noncompliant patients may interrupt a chain of transmission and
      contribute to a decline in the spread of tuberculosis in urban areas.

PMID- 9266874
TI  - Tuberculous pleurisy is more common in AIDS than in non-AIDS patients with
      tuberculosis.
AB  - OBJECTIVE: To investigate the incidence, clinical features, and treatment of
      tuberculous pleurisy in AIDS patients. METHODS: We reviewed all cases of pleural
      tuberculosis in AIDS patients in South Carolina from 1988 through 1994. Clinical
      findings, test results, treatment, and outcome were analyzed. MAIN RESULTS:
      Twenty-two (11%) of the 202 AIDS patients with tuberculosis had pleural
      involvement compared to 6% (169/2,817) pleural involvement in non-AIDS patients
      (p=0.01). Associated features of AIDS tuberculous pleurisy included substantial
      weight loss (7.65+/-1.35 kg) and lower lobe infiltrates (12/22; 55%). No
      difference in pleural fluid characteristics was found when comparing AIDS
      patients with a serum CD4 count > or =200/microL to patients with CD4 count
      <200/microL. Two (9%) of the 22 patients died of tuberculosis. Chest radiograph
      follow-up of 20 patients showed complete resolution in 7, improvement in 10, and
      no improvement in 3. CONCLUSIONS: In South Carolina, pleural involvement is more
      common in AIDS patients than in non-AIDS patients with tuberculosis. Tuberculous
      pleurisy has several atypical features in AIDS patients such as substantial
      weight loss and lower lobe infiltrates. The outcome of treatment is good for most
      patients.

PMID- 9266875
TI  - Variations in medical care for HIV-related Pneumocystis carinii pneumonia: a
      comparison of process and outcome at two hospitals.
AB  - BACKGROUND: Institutional variation in the quality of medical care may be
      evaluated by examining process measures, such as use of diagnostic procedures or
      treatment modalities, or outcome measures, such as mortality. We undertook this
      study to examine variations in both process and outcome of care for patients with
      HIV-related Pneumocystis carinii pneumonia (PCP) at two geographically diverse,
      HIV-experienced, public municipal hospitals. DESIGN: Retrospective review of
      hospitalized patients diagnosed as having PCP cared for at two municipal
      hospitals from 1988 to 1990. At hospital A, charts of all patients diagnosed as
      having PCP were abstracted (n=209); at hospital B, a random sample of 15% were
      abstracted (=136). RESULTS: Among all hospitalized patients diagnosed as having
      PCP, the frequency of making a definitive diagnosis of PCP (as opposed to
      treating empirically) differed markedly at the two hospitals (85% in hospital A
      vs 26% in hospital B; p<0.001), as did the use of intensive care (18% vs 3%;
      p<0.001) and "do-not-resuscitate" orders (39% vs 14%; p<0.001), although the
      timing of starting anti-Pneumocystis medications (89% vs 88% within the first 2
      hospital days) and the use of corticosteroids (21% vs 23%) were similar. Despite
      differences in the process of care, survival rates were similar at the two
      institutions (75% vs 76%; p=0.8) and remained similar when logistic regression
      was used to control for demographic variables and severity of illness (odds ratio
      for survival, hospital B vs A, 1.2 [95% confidence interval, 0.7, 2.0]). The 95%
      confidence intervals (0.7, 2.0), however, were consistent with a considerable
      (and clinically significant) disparity in survival (from 30% lower to a twofold
      higher odds of survival). Sample size calculations showed that a sample of 10
      cases in each hospital would be required to detect the observed difference in
      definitive diagnosis rates (85% vs 26%), but 722 cases in each hospital would be
      required to detect a relevant difference in mortality. CONCLUSIONS: The process
      of care for hospitalized patients with PCP in these two institutions differed
      considerably, but the survival rates were not significantly different, even after
      adjusting for confounding factors. While sample sizes available at the individual
      institutions were sufficient for evaluation of the process of care, they did not
      provide the power necessary to evaluate outcomes. Comparisons of outcomes such as
      mortality between individual hospitals may not have the statistical power to
      exclude important differences.

PMID- 9266876
TI  - Sequential therapy with cefuroxime followed by cefuroxime axetil in community
      acquired pneumonia.
AB  - STUDY OBJECTIVES: To compare the efficacy of two sequential therapy regimens of
      IV cefuroxime followed by oral cefuroxime axetil for the treatment of community
      acquired pneumonia (CAP). DESIGN: Prospective, multicenter, randomized, open
      label, parallel-group study. SETTING: Sixty-six centers in 11 countries (Belgium,
      Canada, Czech Republic, Germany, Hungary, Ireland, Israel, Poland, Portugal,
      South Africa, and the United Kingdom). PATIENTS: Six hundred thirty-six adults
      with CAP requiring hospitalization and initial IV antibiotic treatment.
      INTERVENTIONS: Cefuroxime, 1.5 g IV tid or bid for 48 to 72 h followed by oral
      cefuroxime axetil, 500 mg bid for 7 days. MEASUREMENTS AND RESULTS: For
      clinically evaluable patients, the clinical response rates were equivalent for
      cefuroxime tid and bid groups posttreatment (cure/improvement, 79% and 84%,
      respectively) and at follow-up (maintained cure, 87% and 82%, respectively). All
      signs and symptoms of pneumonia showed improvement at the time of switch from IV
      to oral therapy. A total of 111 pathogens were isolated, the most common being
      Streptococcus pneumoniae (23%), Haemophilus influenzae (18%), and
      Enterobacteriaceae (15%). Bacteriologic clearance was obtained posttreatment in
      47 of 49 and 36 of 42 of bacteriologically evaluable patients in the cefuroxime
      tid and bid groups, respectively. Both regimens were well tolerated with a low
      incidence of drug-related adverse events, the most common being GI. CONCLUSIONS:
      Twice daily IV cefuroxime followed by oral cefuroxime axetil is a simple and
      effective sequential therapy regimen for the treatment of CAP. It offers
      potential cost savings and can replace the current tid regimen in this
      indication.

PMID- 9266878
TI  - CT-guided fine-needle aspiration cytology of solitary pulmonary nodules: a
      prospective, randomized study of immediate cytologic evaluation.
AB  - STUDY OBJECTIVE: To evaluate the immediate cytologic assessment during CT-guided
      fine-needle aspiration cytology (FNAC) in the diagnosis of operable indeterminate
      solitary pulmonary nodules (SPNs). DESIGN: Prospective randomized study. PATIENTS
      AND METHODS: Two hundred twenty patients with SPN undergoing CT-guided FNAC were
      divided into two groups. In the first one (group A, 110 patients), a cytologist
      assessed the adequacy of the sample obtained immediately, and when the sample was
      considered inadequate, fine-needle aspiration (FNA) was repeated. In the second
      group (B, 110 patients), an immediate cytologic examination was not performed,
      but only a gross assessment by the surgeon. Histologic study of the SPN was
      possible in 217 cases, whereas three patients were followed up radiologically.
      RESULTS: Adequate samples were obtained in 100% of group A and 88% of group B
      (p<0.001). The diagnostic accuracy was 99% in group A and 81% in group B
      (p<0.001). Group A required a mean of 1.22 FNAs compared with 1.10 in group B
      (p=0.015). The rate of pneumothorax in the whole series was 24%, and
      statistically significant differences between the two groups were not detected.
      CONCLUSIONS: Immediate cytologic study significantly increased the adequacy and
      diagnostic accuracy of CT-guided FNAC of indeterminate SPNs without causing a
      significant increase of complications.

PMID- 9266877
TI  - Likelihood of malignancy in a solitary pulmonary nodule: comparison of Bayesian
      analysis and results of FDG-PET scan.
AB  - OBJECTIVE: To compare the probability of cancer in a solitary pulmonary nodule
      using standard criteria with Bayesian analysis and result of 2-[F-18] fluoro-2
      deoxy-D-glucose-positron emission tomographic (FDG-PET) scan. SETTING: A
      university hospital and a teaching Veteran Affairs Medical Center. METHODS:
      Retrospective analysis of 52 patients who had undergone both CT scan of the chest
      and a FDG-PET scan for evaluation of a solitary pulmonary nodule. FDG-PET scan
      was classified as abnormal or normal. Utilizing Bayesian analysis, the
      probability of cancer using "standard criteria" available in the literature,
      based on patient's age, history of previous malignancy, smoking history, size and
      edge of nodule, and presence or absence of calcification were calculated and
      compared to the probability of cancer based on an abnormal or normal FDG-PET
      scan. Histologic study of the nodules was the gold standard. RESULTS: The
      likelihood ratios for malignancy in a solitary pulmonary nodule with an abnormal
      FDG-PET scan was 7.11 (95% confidence interval [CI], 6.36 to 7.96), suggesting a
      high probability for malignancy, and 0.06 (95% CI, 0.05 to 0.07) when the PET
      scan was normal, suggesting a high probability for benign nodule. FDG-PET scan as
      a single test alone was more accurate than the standard criteria and standard
      criteria plus PET scan in correctly classifying nodules as malignant or benign.
      CONCLUSION: FDG-PET scan as a single test was a better predictor of malignancy in
      solitary pulmonary nodules than the standard criteria using Bayesian analysis.
      FDG-PET scan can be a useful adjunct test in the evaluation of solitary pulmonary
      nodules.

PMID- 9266879
TI  - Origin of pleural cells after lung transplantation: from donor or recipient?
AB  - We evaluated the change in the percentage of cells of donor origin in pleural
      fluid of 13 consecutive patients who underwent lung transplantation. Pleural
      fluid was sampled 2, 4, and 8 days after lung transplantation. DNA, which was
      extracted from the blood of donors and recipients and from the pleural fluid, was
      amplified using a polymerase chain reaction technique. The reaction products were
      electrophoresed, and bands indicating amplified human leukocyte antigen (HLA)-DR
      alleles were quantified by determining the area under the curve (AUC) by a
      densitometric analysis. HLA-DR alleles, which were present only in recipient
      cells (recipient allele), were analyzed and compared to HLA-DR alleles that were
      present only in donor cells (donor allele). A dilution study was first performed
      to provide a standard curve relating the percentage of donor and recipient cells
      in a mixture to their AUC. The AUC of the recipient alleles did not change
      significantly over the first 8 postoperative days. The AUC of the donor alleles
      was less on postoperative days 4 and 8 than on day 2 (p<0.05). The donor allele
      AUC on day 8 was <20% of the shared allele AUC, corresponding to <1% of all cells
      by the dilution study. We conclude that donor cells are rapidly cleared from the
      pleural space after lung transplantation, with <1% of cells of donor origin by
      postoperative day 8.

PMID- 9266880
TI  - Prospective randomized trial of talc slurry vs bleomycin in pleurodesis for
      symptomatic malignant pleural effusions.
AB  - OBJECTIVE: Symptomatic malignant pleural effusions are common sequelae in
      patients with certain malignancies. Pleurodesis via bedside thoracostomy is the
      current treatment option most commonly used. To our knowledge, this is the first
      prospective randomized trial to examine which agent, bleomycin or talc slurry, is
      superior in terms of effectiveness, safety, and cost. PATIENTS AND METHODS:
      Between July 1992 and March 1995, 35 patients presenting to our medical center
      with symptomatic malignant pleural effusions were prospectively randomized to
      undergo chemical pleurodesis with either bleomycin or talc slurry via bedside
      thoracostomy. The conditions of patients were assessed and graded before and
      after treatment concerning pain, dyspnea, and chest radiographs. RESULTS: Twenty
      nine patients who underwent 33 treatments (14 with bleomycin and 19 with talc)
      were available for follow-up. Follow-up ranged from 2 weeks to 8 months (mean,
      1.7 months). Both groups demonstrated notable improvement in both pain and
      dyspnea following treatment, but there were no statistically significant
      differences between groups in the amount of improvement (two-tailed Student's t
      test). Permanent control of effusions, defined objectively on chest radiograph,
      was achieved with 11 bleomycin treatments (79%) and 17 talc treatments (90%)
      (p=0.388). The procedures were well tolerated and no significant adverse effects
      were observed. Talc is a much less costly agent than bleomycin ($12.36 cost to
      our medical center per treatment for talc vs $955.83 for bleomycin). CONCLUSION:
      Given the similar efficacy and significant cost advantage, we conclude that talc
      is the agent of choice when utilizing pleurodesis for control of symptomatic
      malignant pleural effusions.

PMID- 9266881
TI  - Iron accumulation in lung allografts after transplantation.
AB  - Lung transplantation has become a therapeutic option for end-stage pulmonary
      diseases, but after transplantation, infections and obliterative bronchiolitis
      (OB) are major causes of long-term morbidity and mortality. OB is a
      fibroproliferative disease, of poorly understood etiology, characterized by an
      irreversible decline in allograft function. Because diseases with tissue iron
      overload are characterized by fibrosis and end-organ failure, we studied the iron
      concentrations in BAL fluid and lung tissue in 10 lung allograft patients. BAL
      fluid revealed significantly elevated iron concentrations in allograft patients
      compared with five normal volunteers (135+/-16.54 micromol/L vs 33.65+/-7.48
      micromol/L, respectively). Prussian blue staining of biopsy specimens of lung
      allograft tissue revealed an accumulation of iron primarily in alveolar
      macrophages. Immunohistochemical stains for ferritin revealed accumulation of the
      protein in macrophages, interstitium, vascular walls, and bronchiolar epithelium.
      Iron studies of the blood (serum ferritin and iron concentrations) revealed no
      evidence for systemic iron overload. In conclusion, patients with pulmonary
      allografts appear to have elevated concentrations of iron in lung tissue. This
      iron overload may place the allografts at increased risk of metal-mediated injury
      and fibrosis.

PMID- 9266882
TI  - Hemoptysis: etiology, evaluation, and outcome in a tertiary referral hospital.
AB  - OBJECTIVES: Hemoptysis, an important and alarming symptom, often indicates
      serious disease. This study was designed to assess the different causes of
      hemoptysis, the relative importance of the different diagnostic modalities
      employed, and the outcome in an Israeli population cohort. DESIGN: A
      retrospective analysis of 208 patients with hemoptysis at the Hadassah University
      Hospital, Jerusalem, Israel between January 1980 and August 1995. RESULTS:
      Bronchiectasis (20%), lung cancer (19%), bronchitis (18%), and pneumonia (16%)
      accounted for most causes of hemoptysis. In contrast to older studies, active
      tuberculosis was a rare finding (1.4%). Bronchiectasis and bleeding diathesis
      were major causes of moderate to severe hemoptysis while bronchitis and lung
      cancer were commonly associated with milder degrees of bleeding. CT scan was the
      most sensitive diagnostic test when employed alone, with a positive yield of 67%.
      However, it failed to locate at least three cases of lung cancer. When combining
      a CT study together with a bronchoscopy, the positive yield increased to 93%. The
      mortality rate for patients with mild to moderate hemoptysis was low (2.5% and
      6%, respectively), while patients with massive hemoptysis had high mortality
      rates (38%). Patients with lung cancer or bleeding diathesis had higher mortality
      rates compared with the rest of the cohort. CONCLUSIONS: Hemoptysis is a common
      symptom with a good prognosis in most cases. However, patients exhibiting massive
      bleeding or those with lung malignancy and patients with bleeding diathesis had a
      poorer prognosis. Patients older than 50 years with a positive smoking history
      need an extensive evaluation and follow-up to exclude lung carcinoma. The
      combined use of bronchoscopy and chest CT has the best yield in evaluating
      hemoptysis.

PMID- 9266883
TI  - The diagnosis of ventilator-associated pneumonia: a comparison of histologic,
      microbiologic, and clinical criteria.
AB  - STUDY OBJECTIVE: To evaluate histologic, microbiological, and clinical criteria
      in the recognition of ventilator-associated pneumonia (VAP) in patients who died
      while mechanically ventilated. METHODS: The study group consisted of 39 patients
      who died after a mean of 14 days of mechanical ventilation. Postmortem fiberoptic
      bronchoscopy (FOB) and open lung biopsy were performed with collection of
      specimens initiated <1 h after death. The microbiological specimens included
      suction catheter aspirate of tracheal secretions, FOB-guided protected specimen
      brush (PSB) of tracheal secretions, blindly placed PSB in a distal airway, FOB
      guided PSB in a distal airway, and FOB-guided BAL fluid (BALF) in a distal
      airway. Qualitative bacteriologic study was performed on all specimens, and
      quantitative bacteriologic study was performed on all but the suction catheter
      aspirate of the trachea. A biopsy specimen of peripheral lung parenchyma from the
      same region sampled by FOB was sent for quantitative culture and histologic
      analysis. The BALF was analyzed for cell population and percent of neutrophils
      containing intracellular organisms. The clinical criteria selected for comparison
      with histologic and microbiological results included a temperature > or =38.5
      degrees C during the 48 h prior to death, a WBC count > or =15,000/mm3 in the 48
      h prior to death, presence of a bacterial or fungal pathogen on the last sputum
      culture, radiographic worsening in the week prior to death, and worsening gas
      exchange defined as a 15% decrease in the PaO2/fraction of inspired oxygen ratio
      in the 72 h prior to death. RESULTS: None of the quantitative cultures had a
      reliable positive predictive value for histologic pneumonia. None of the five
      clinical criteria tested showed agreement with the presence or absence of
      histologic pneumonia. There was a significant correlation between qualitative and
      quantitative microbiological results from the distal airway/FOB-guided PSB,
      distal airway/BALF, and quantitative culture of the lung parenchyma. Also,
      suction catheter aspirate of the trachea had a sensitivity of 87% in recognizing
      the bacterial species simultaneously present in lung parenchyma. None of the
      patients with histologic pneumonia had <50% neutrophils in the BALF. CONCLUSIONS:
      Neither the bacterial, density from the four airway quantitative cultures, nor
      the bacterial density from quantitative culture of lung parenchyma accurately
      separated the histologic pneumonia and nonpneumonia groups. No clinical criteria
      or combination of clinical criteria correlated with the presence or absence of
      histologic pneumonia. A BALF with <50% neutrophils had a 100% negative predictive
      value for histologic pneumonia. A BALF quantitative culture had a sensitivity of
      63%, specificity of 96%, and positive predictive value of 91% in recognizing
      sterile lung parenchyma. Thus, BALF may have a role in excluding
      pneumonia/infection in the ventilated patient. Antibiotic choice for the empiric
      therapy of VAP can be accurately guided by the microbial population recognized
      through culture of a tracheal suction catheter aspirate.

PMID- 9266884
TI  - Reproducibility of the histologic diagnosis of pneumonia among a panel of four
      pathologists: analysis of a gold standard.
AB  - STUDY OBJECTIVE: To establish a histologic diagnosis of pneumonia by consensus of
      a panel of pathologists, to test the interobserver and intraobserver variation in
      the histologic diagnosis of pneumonia, to compare the diagnostic accuracy of
      diagnosing pneumonia with and without preselected histologic criteria, and to
      establish more specific histologic criteria for the diagnosis of pneumonia.
      METHODS: The study group consisted of 39 patients who died after a mean of 14
      days of mechanical ventilation. A postmortem open lung biopsy was performed on
      all patients. The tissue was reviewed independently by four pathologists who
      categorized the slides from each patient as showing or not showing pneumonia.
      Interobserver variation was calculated using the kappa statistic. Six months
      following the initial evaluation, the same slides were resubmitted to one of the
      pathologists for reevaluation to look for intraobserver error. Finally, the
      slides were reviewed and categorized by the criteria of Johanson et al into no
      pneumonia, mild, moderate, or severe bronchopneumonia. A comparison was made of
      the patients selected as demonstrating histologic pneumonia by each of the
      examinations. RESULTS: The reliability coefficient (kappa) measuring agreement
      among the four pathologists was good at 0.916. However, the prevalence of
      pneumonia as determined by each of the four pathologists varied; pathologist A,
      15 of 39 (38%); pathologist B, 12 of 39 (31%); pathologist C, 9 of 39 (23%); and
      pathologist D, 7 of 39 (18%). Resubmitting the same slides to the same
      pathologist 6 months later resulted in reclassification of 2 of 39 patients.
      Using the histologic criteria of Johanson and colleagues, 14 patients were
      selected as having pneumonia compared with only nine patients selected by
      consensus of three of four pathologists. CONCLUSIONS: Recognition of histologic
      pneumonia varies among pathologists. The preselected criteria of Johanson and
      colleagues detected histologic pneumonia in eight of nine patients picked by
      consensus of pathologists, but six additional patients classified as "no
      histologic pneumonia" by the consensus of pathologists were judged to have
      histologic pneumonia by these criteria. The results established the necessity for
      standardization of histologic criteria for studies using biopsy as the gold
      standard for bacterial pneumonia. An atlas showing the criteria used in our
      selection was developed.

PMID- 9266886
TI  - The effect of sepsis on breathing pattern and weaning outcomes in patients
      recovering from respiratory failure.
AB  - OBJECTIVE: To determine the effects of sepsis on breathing pattern and weaning
      outcome in medical patients recovering from respiratory failure. DESIGN:
      Prospective, observational study. SETTING: Medical ICU of a 300-bed community
      teaching hospital. MEASUREMENTS: Patients were classified as having sepsis or not
      having sepsis on the first day of weaning. The respiratory rate:tidal volume
      ratio (RVR), maximal inspiratory pressure (MIP), respiratory system mechanics,
      minute volume, WBC count, and maximal temperature (Tmax) were recorded for the
      first day of weaning. Weaning was then conducted by the patients' primary
      physicians; weaning outcomes and days spent receiving mechanical ventilation were
      recorded. RESULTS: Sixty patients were studied over 64 separate ICU admissions.
      Twenty-five patients met criteria for sepsis and had a higher mean APACHE II
      (acute physiology and chronic health evaluation) score than patients without
      sepsis (mean+/-SE: 23.4+/-1.3 vs 18.7+/-1.0; p<0.05). Respiratory mechanics, age,
      and minute volumes were not different between patients with and without sepsis.
      Patients with sepsis had a higher RVR than patients without sepsis (94.3+/-10.1
      vs 66.6+/-6.4 breaths/min/L; p<0.05) and tended to have a lower MIP (25.0+/-2.0
      vs 31.0+/-2.3 cm H2O; p=0.055). The MIP and RVR were moderately correlated
      (r=0.50, p<0.001). WBC count and Tmax did not correlate with RVR in the total
      population or in sepsis/nonsepsis subpopulations. First-day weaning success was
      higher in patients without sepsis (17/39=44%) than patients with sepsis
      (6/25=24%; odds ratio=2.4; 95% confidence interval=0.8 to 7.3). Patients with
      sepsis tended to require a longer duration of weaning (3.8+/-0.6 vs 2.5+/-0.5
      days; p=0.1) and mechanical ventilation (7.4+/-1.0 vs 5.6+/-1.0 days; p=0.2) than
      patients without sepsis. Differences were not significant when patients were
      stratified by ICU admission APACHE II scores. CONCLUSIONS: Patients recovering
      from sepsis breathe with a higher RVR, tend to have a lower MIP, and tend to be
      more likely to encounter first-day weaning failure compared to patients without
      sepsis. Our data also suggest that the severity of illness on ICU admission could
      explain some of these differences.

PMID- 9266885
TI  - Value of C-reactive protein in the detection of bacterial contamination at the
      time of presentation in drug-induced aspiration pneumonia.
AB  - STUDY OBJECTIVES: To compare the plasma concentration of C-reactive protein (CRP)
      with traditional markers for diagnosis of bacterial pneumonia in patients with
      suspected aspiration. DESIGN: Prospective, nonrandomized, controlled study of
      consecutive hospital admissions. SETTING: Toxicology ICU in a university
      hospital. PATIENTS OR PARTICIPANTS: Acutely poisoned comatose patients admitted
      to the hospital with suspicion of aspiration pneumonia. INTERVENTIONS: Distal
      protected catheter sampling per fiberoptic bronchoscopy and bacteriologic culture
      were employed as a standard to detect the bacterial component of suspected
      aspiration pneumonia. Plasma CRP concentrations, temperature, and WBC count were
      measured on hospital day 1. MEASUREMENTS AND RESULTS: Sixty-six patients were
      evaluated. Thirty-two had bacterial contamination by positive culture (> or
      =10(3) cfu/mL). Multiple receiver-operating characteristic (ROC) curves were used
      to compare each parameter for detection of infection secondary to aspiration. The
      ROC curve of CRP concentrations showed that a CRP >75 mg/L is associated with
      bacterial contamination with a sensitivity of 87%, specificity of 76%, positive
      predictive value of 78%, and negative predictive value of 87%. ROC curves of
      temperature and WBC count demonstrated poor diagnostic value of these markers in
      indicating the bacterial component of suspected aspiration pneumonia.
      CONCLUSIONS: Early measurement of CRP is useful for the diagnosis of aerobic
      bacterial content of aspiration pneumonia and perhaps in determining the need for
      invasive bacteriologic sampling. Temperature and WBC count are poor indicators of
      bacterial infection of aspiration pneumonia in poisoned patients.

PMID- 9266887
TI  - Inhaled nitric oxide does not change transpulmonary angiotensin II formation in
      patients with acute respiratory distress syndrome.
AB  - STUDY OBJECTIVE: To investigate the effect of short-term inhalation of nitric
      oxide (NO) on transpulmonary angiotensin II formation in patients with severe
      ARDS. DESIGN: Prospective, clinical study. SETTING: Anesthesiology ICU of a
      university hospital. PATIENTS: Ten ARDS patients who responded to inhalation of
      100 ppm NO by decreasing their pulmonary vascular resistance (PVR) by at least 20
      dyne x s x cm(-5) were included in the study. INTERVENTIONS AND MEASUREMENTS: In
      addition to standard treatment, the patients inhaled 0, 1, and 100 ppm NO in 20
      min intervals. Fraction of inspired oxygen was 1.0. Hemodynamics were measured
      and recorded online. Mixed venous (pulmonary arterial catheter) and arterial
      (arterial catheter) blood samples were taken simultaneously for hormonal analyses
      at the end of each inhalation period. RESULTS: Pulmonary arterial pressure
      decreased from 33+/-2 mm Hg (0 ppm NO, mean+/-SEM) to 29+/-2 mm Hg (1 ppm NO,
      p<0.05), and to 27+/-2 mm Hg (100 ppm NO, p<0.05, vs 0 ppm). PVR decreased from
      298+/-56 (0 ppm NO) to 243+/-45 dyne x s x cm(-5) (1 ppm NO, not significant
      [NS]), and to 197+/-34 dyne x s x cm(-5) (100 ppm NO, p<0.05, vs 0 ppm). Arterial
      oxygen pressure increased from 174+/-23 mm Hg (0 ppm NO) to 205+/-26 mm Hg (1 ppm
      NO, NS), and to 245+/-25 mm Hg (100 ppm NO, p <0.05, vs 0 ppm). Mean plasma
      angiotensin II concentrations were 85+/-20 (arterial) and 57+/-13 pg/mL (mixed
      venous) during 0 ppm NO and did not change during inhalation of 1 and 100 ppm NO.
      Mean transpulmonary plasma angiotensin II concentration gradient (=difference
      between arterial and mixed venous blood values) was 28+/-8 pg/mL (range, 0 to 69)
      during 0 ppm NO and did not change during inhalation of 1 and 100 ppm NO. Mean
      transpulmonary angiotensin II formation (transpulmonary angiotensin II gradient
      multiplied with the cardiac index) was 117+/-39 ng/min/m2 (range, 0 to 414)
      during 0 ppm NO and did not change during inhalation of 1 and 100 ppm NO. Mean
      arterial plasma cyclic guanosine monophosphate concentration was 11+/-2 pmol/mL
      (0 ppm NO), did not change during 1 ppm NO, and increased to 58+/-8 pmol/mL (100
      ppm NO, p<0.05). Arterial plasma concentrations of aldosterone (142+/-47 pg/mL),
      atrial natriuretic peptide (114+/-34 pg/mL), angiotensin-converting enzyme (30+/
      5 U/L), and plasma renin activity (94+/-26 ng/mL/h of angiotensin I) did not
      change. CONCLUSION: The decrease of PVR by short-term NO inhalation in ARDS
      patients was not accompanied by changes in transpulmonary angiotensin II
      formation. Our results do not support any relationship between transpulmonary
      angiotensin II formation and the decrease in PVR induced by inhaled NO.

PMID- 9266888
TI  - Efficacy of metered-dose inhaler administration of albuterol in intubated
      infants.
AB  - STUDY OBJECTIVE: To compare the safety and efficacy of metered-dose inhaler (MDI)
      albuterol to nebulized (NEB) albuterol administration. DESIGN: A randomized,
      triple-blinded, crossover study. SETTING: A pediatric ICU in a tertiary care
      children's hospital. PATIENTS: Eleven intubated infants with bronchiolitis.
      INTERVENTIONS: Subjects received four puffs of MDI albuterol (360 microg) and 3
      mL of NEB saline solution placebo or 0.3 mL of NEB albuterol (1.5 mg) and MDI
      saline solution placebo. Each set of albuterol and saline solution placebo was
      administered after direct attachment of delivery device to the endotracheal tube
      and bag-valve system. Subjects received the opposite sequence 4 h after the
      initial sequence. The second sequence was given first the next day, and the first
      sequence was administered 4 h later. MEASUREMENTS AND RESULTS: Respiratory system
      compliance and resistance were measured at baseline and 30 min, 1 h, 2 h, and 4 h
      after each set of placebo and albuterol. There was an appreciable improvement in
      compliance and resistance for up to 2 h following both methods of administration.
      However, the degree of improvement was not significantly different (p>0.05)
      between the two methods. Neither method caused a significant change in resistance
      when measured at 4 h after albuterol/placebo administration. No evidence of
      toxicity was detected. CONCLUSIONS: MDI-administered albuterol is as safe and
      efficacious as nebulized-administered albuterol in intubated infants with
      bronchiolitis. Generalizability of these results is limited by differences in
      drug delivery with different brands of nebulizers and spacers and sites of
      attachment.

PMID- 9266890
TI  - Flow-proportional administration of nitric oxide with a new delivery system:
      inspiratory nitric oxide concentration fluctuation during different flow
      conditions.
AB  - OBJECTIVE: To evaluate the accuracy of a flow-proportional delivery system and
      the pattern of inspiratory nitric oxide (NO) concentration during different flow
      conditions. DESIGN: Laboratory study in a lung model. SETTING: University
      experimental laboratory. SUBJECT: With a new delivery system, NO was administered
      proportional to the inspiratory flow into the inspiratory circuit to deliver a NO
      concentration of 10 and 30 ppm to a test lung during different ventilatory modes
      (volume-controlled ventilation [VCV], pressure-controlled ventilation [PCV], and
      airway pressure release ventilation [APRV]) with a fraction of inspired oxygen
      (FIO2) of 1.0. INTERVENTIONS: During VCV and PCV, the flow pattern was varied to
      achieve tidal volumes of 300, 600, and 900 mL, respectively, with inspiratory to
      expiratory time ratios of 1:3, 1:2, and 1:1. APRV was studied at a minute volume
      of 6, 12, and 18 L. Nitric oxides (NOx [NO+NO2]) and nitric dioxide (NO2) were
      monitored by chemiluminescence and electrochemical analysis. As the NO/N2 gas
      mixture is the only nitrogen source during ventilation with an FIO2 analyzer.
      RESULTS: During all flow conditions, NOx concentration was stable but slightly
      higher than expected. Measured and expected mean concentrations differed <9%
      (mean, <4%). Inspiratory NOx concentration fluctuation derived from N2
      concentration was significantly higher than expected at higher flow rates, but
      this difference was not detected by chemiluminescence or electrochemical
      analysis. The NO2 production was not affected by the flow rate and was always <
      or =0.2 ppm (NO, 10 ppm) and < or =1.9 ppm (NO, 30 ppm). CONCLUSION: The tested
      NO delivery module administered stable mean inspiratory NO concentrations.
      Although inspiratory NO concentration fluctuates depending on the inspiratory
      flow rate, this delivery device allows stable NO administration without requiring
      adjustments when ventilator settings are changed.

PMID- 9266889
TI  - Gut decontamination reduces bowel ischemia-induced lung injury in rats.
AB  - OBJECTIVE: To evaluate the effects of gut decontamination on endotoxin, tumor
      necrosis factor (TNF) levels, and the associated lung injury in a rat model of
      bowel ischemia. SUMMARY BACKGROUND DATA: Gut ischemia induces disruption of the
      intestinal mucosal barrier, allowing translocation of bacteria and endotoxin into
      the blood, which may trigger a systemic inflammatory response and lung injury.
      METHODS: Thirty anesthetized rats were randomized into three groups: (1) ischemia
      reperfusion (I/R) alone (a 60-min superior mesenteric artery occlusion and 4 h of
      reperfusion, n=10); (2) rats that underwent gut decontamination prior to ischemia
      (I/R+GD, n=10); and (3) control rats (sham operated, n=10). Serum levels of
      lipopolysaccharide (LPS) and TNF were measured at the end of the experiment. Lung
      permeability was measured using bovine serum albumin labeled with 125I, and organ
      injury was assessed histologically. RESULTS: One hour of bowel ischemia and 4 h
      of reperfusion (I/R) led to elevations of blood LPS and TNF levels of 0.33+/
      0.005 EU/mL and 173+/-56 pg/mL, which were higher than the sham group (p<0.01).
      Gut decontamination (I/R+GD) significantly attenuated the LPS and TNF generation,
      0.09+/-0.005 and 56.2+/-6 pg/mL (p<0.01). Lung injury as assessed by pulmonary
      permeability index was also reduced by gut decontamination, 2.1+/-0.42 vs 5.3+/
      0.82 in the control group (p<0.03). Surprisingly no difference was detected in
      the number of pulmonary neutrophils in sequestration between the groups.
      CONCLUSIONS: Our data suggest that gut decontamination can reduce the generation
      of LPS, TNF, and the severity of lung damage that often follows ischemia and
      reperfusion of the intestine in rats.

PMID- 9266891
TI  - Airway inflammation in COPD assessed by sputum levels of interleukin-8.
AB  - STUDY OBJECTIVE: To assess the characteristics of airway inflammation in patients
      with COPD. METHODS: We measured the sputum concentration of interleukin-8 (IL-8),
      a chemokine involved in the migration and activation of neutrophils and
      eosinophils. We also measured myeloperoxidase (MPO) as a parameter of neutrophil
      activity and eosinophil cationic protein (ECP) as a parameter of eosinophil
      activity. Spontaneous sputum samples were obtained from 33 patients with stable
      COPD and 30 patients with asthma. Induced sputum samples were obtained from 12
      normal control subjects. RESULTS: The sputum concentration of IL-8 was
      significantly higher in the patients with COPD than in the patients with asthma
      or in the control subjects (p<0.0001). Concentrations of MPO and ECP were
      significantly higher in the patients with COPD than in the control subjects but
      did not differ significantly between the patients with COPD and those with
      asthma. In the patients with COPD, the sputum concentration of IL-8 was
      significantly correlated with the concentration of MPO (r=0.55, p<0.001) and of
      ECP (r=0.53, p<0.01). The sputum concentration of IL-8 was negatively correlated
      with FEV1/FVC (r=-0.78, p<0.0001) in the COPD group. CONCLUSIONS: Results suggest
      the activation of both neutrophils and eosinophils in the airways of patients
      with COPD. It appears that IL-8 plays a primary role in this activation. The
      sputum concentration of IL-8 appeared to be closely associated with the degree of
      airflow obstruction in patients with COPD and may serve as a marker in evaluating
      the severity of airway inflammation, which is a risk factor for COPD.

PMID- 9266892
TI  - Primary mediastinal tumors. Part 1: tumors of the anterior mediastinum.
AB  - Primary anterior mediastinal neoplasms comprise a diverse group of tumors and
      account for 50% of all mediastinal masses. Thymomas are most common and can be
      locally invasive and associated with parathymic syndromes. Thymic carcinomas and
      thymic carcinoids are rare malignancies with a propensity for local invasion and
      distant metastases. Thymolipomas are benign thymic tumors. The mediastinal germ
      cell tumors are a heterogeneous group of benign and malignant neoplasms.
      Mediastinal lymphangiomas are rare tumors and predominantly occur in young
      children. In contrast, mediastinal goiters are relatively common in adults.
      Mediastinal parathyroid adenomas are an uncommon cause of persistent
      hyperparathyroidism and rarely cause a discernible mass. The clinical,
      radiologic, and therapeutic aspects of the most common masses are reviewed.

PMID- 9266893
TI  - Does the mast cell still have a key role in asthma?
AB  - In recent years, the emerging concept of bronchial inflammation as a prominent
      histopathologic characteristic of asthma has profoundly modified the view of the
      role of the mast cell, which was traditionally thought to be linked to the
      release of soluble chemical mediators substantially involved in the genesis of
      acute, immediate bronchospasm. The finding that the production of proinflammatory
      cytokines by mast cells in asthmatic airways is comparable, in some
      circumstances, to that of T-cell origin, has led to the hypothesis that mast
      cells, along with T lymphocytes and eosinophils, may also contribute to the
      genesis of chronic, persistent asthma. This hypothesis is further supported by
      the finding that mast cells are able to functionally interact with B cells
      (promoting IgE synthesis) and T lymphocytes (acting as antigen presenting cells),
      thus taking part in the immune network. Moreover, mast cells produce an exclusive
      family of proteases (tryptases and chymases) that exert many biological actions
      relevant to airways inflammation and remodeling. Future studies will better
      explain the role of mast cells in asthma and, more specifically, the links with
      bone marrow-where mast cell progenitors originate-and the airways, where mast
      cells develop, differentiate, and assume the functions of mature cells. This
      article reviews recent data available on these topics.

PMID- 9266894
TI  - A case of unilateral diaphragmatic eventration treated by plication with
      thoracoscopic surgery.
AB  - A 56-year-old woman underwent plication with U-stitches by thoracoscopic surgery
      for left diaphragmatic eventration. Marked improvement in left lung expansion,
      normalization of the position of the left diaphragm on chest radiograph, and
      improvement of pulmonary function and dyspnea on exertion have been maintained
      for 2 years. Plication for diaphragmatic eventration should be performed with
      minimally invasive surgery.

PMID- 9266895
TI  - A man with neck stiffness and disconjugate gaze.

PMID- 9266896
TI  - The case of the torpid thoracic tumor.

PMID- 9266897
TI  - Progressive somnolence leading to coma in a 68-year-old man.

PMID- 9266898
TI  - Chronic necrotizing pulmonary aspergillosis: approach to management.
AB  - OBJECTIVE: To describe our experience with 6 patients and to review the current
      literature to update the approach to the diagnosis and treatment of chronic
      necrotizing pulmonary aspergillosis. DESIGN: Patient reports and MEDLINE review
      of English-language literature published after 1980. RESULTS: Chronic necrotizing
      pulmonary aspergillosis (CNPA) is a subacute infection most commonly seen in
      patients with altered local defense from preexisting pulmonary disease or in
      patients with risk factors that alter systemic immune status. Delays in diagnosis
      are common. Although initial reports advocated intravenous amphotericin B,
      itraconazole has emerged as a better initial therapy because of its documented
      efficacy and minimal toxicity. The dose and duration of therapy should be based
      on clinical response. In patients who do not respond to medical therapy,
      pulmonary resection can be considered, but postoperative morbidity is high.
      Recurrent or relapsing infections occur; chronic maintenance therapy with
      itraconazole can be considered in patients with residual parenchymal scarring. A
      wide range of mortality rates has been reported for CNPA. Outcome is most likely
      influenced by severity of comorbid conditions, extent of underlying pulmonary
      disease, delays in diagnosis, and initiation of effective therapy.

PMID- 9266899
TI  - Bronchioloalveolar carcinoma in a child with congenital cystic adenomatoid
      malformation.
AB  - An 11-year-old girl was evaluated for chest pain, and chest radiographic findings
      of multiple nodules throughout both lungs. She underwent resection of several of
      the lesions from her left lung, which were found at pathologic examination to be
      bronchioloalveolar carcinoma. Her previous medical history included incomplete
      resection of a type I congenital cystic adenomatoid malformation in the neonatal
      period. To our knowledge, this girl is the youngest reported case of
      bronchioloalveolar carcinoma in a nonimmunocompromised patient, and one of
      several in which the association of congenital cystic adenomatoid malformation
      and bronchioloalveolar carcinoma has been observed.

PMID- 9266901
TI  - Hyperplasia of pulmonary neuroendocrine cells in a case of childhood pulmonary
      emphysema.
AB  - Pulmonary emphysema is very uncommon in children in the first decade of life. The
      few cases documented in the literature were all due to alpha1-antitrypsin
      deficiency. We present the case of a 6-year-old white boy with chronic cough and
      dyspnea on exertion. Lung biopsy showed panacinar type emphysema with patent
      airways and diffuse hyperplasia of pulmonary neuroendocrine cells revealed after
      immunostaining for bombesin, a peptide produced by these cells. We speculate that
      idiopathic diffuse hyperplasia of bombesin-producing pulmonary neuroendocrine
      cells may contribute to the pathogenesis of unusual COPD in childhood.

PMID- 9266900
TI  - Primary pulmonary hypertension in a patient with CD8/T-cell large granulocyte
      leukemia: amelioration by cladribine therapy.
AB  - We report a case of primary pulmonary hypertension in an adult man with CD8/T
      cell large granulocyte leukemia. Successful treatment of his leukemia with
      cladribine resulted in dramatic and sustained improvement of his pulmonary
      hypertension.

PMID- 9266902
TI  - Torsade de pointes and prolonged QT interval from surreptitious use of sotalol:
      use of drug levels in diagnosis.
AB  - Torsade de pointes is a well-established toxic effect of sotalol hydrochloride.
      In a patient presenting with torsade de pointes and a long QTc interval of
      unknown cause, a serum sotalol level was used to secure an otherwise difficult
      diagnosis.

PMID- 9266903
TI  - Lung herniation through a postthoracoscopy chest wall defect: demonstration with
      spiral CT.
AB  - The incidence of complications following thoracoscopy is approximately 10%, the
      most prevalent being prolonged air leak and chest pain. We report two cases of
      lung herniation through the chest wall defect created by thoracoscopy. Use of the
      Valsalva maneuver during CT scanning is recommended as a diagnostic imaging
      method in cases with suspected lung herniation.

PMID- 9266904
TI  - Portable power supply for continuous mechanical ventilation during intrahospital
      transport of critically ill patients with ARDS.
AB  - Patients with respiratory failure and poor pulmonary compliance requiring high
      levels of positive pressure ventilation are at high risk during intrahospital
      transportation. Most ICU ventilators currently do not have a built-in power
      supply. Manual bag-valve ventilation frequently is used but often without optimum
      mean airway pressures or minute ventilation guarantees. Transport ventilators
      also are limited in their ability to provide high positive end-expiratory
      pressure, variable inspiratory-expiratory ratios, or pressure-controlled
      ventilation. The 3M SARNS HELP (Hospital Emergency Limited Power) 115, a portable
      battery, provides continuous power to ICU ventilators and eliminates ventilator
      circuit interruption for the critical period of patient transportation.

PMID- 9266905
TI  - Chronic lithoptysis with multiple bilateral broncholiths.
AB  - A case of chronic lithoptysis with unusual features was undiagnosed for 20 years.
      The presence of multiple broncholiths in different segments of both lungs, not
      previously described, was confirmed endoscopically. Areas of unusual mucosal
      punctate calcifications, not appreciated on concurrent high-resolution CT scan,
      also are described.

PMID- 9266906
TI  - Other potential uses for cardiopulmonary bypass.

PMID- 9266907
TI  - Medical meetings: a chance for braindusting.

PMID- 9266908
TI  - Oxygen deficit during exercise testing.

PMID- 9266909
TI  - Group II phospholipase A2 and pulmonary histiocytosis X.

PMID- 9266910
TI  - Simultaneous administration of inhaled nitric oxide in two children with
      pulmonary hypertension.

PMID- 9266911
TI  - Pleural alkaline phosphatase in separation of transudative and exudative pleural
      effusions.

PMID- 9266912
TI  - More on myocardial contusion--with additional insight on myocardial concussion.

PMID- 9266913
TI  - Salvage chemotherapy for recurrent invasive thymoma.

PMID- 9266914
TI  - The changing presentation of lung adenocarcinoma.

PMID- 9266915
TI  - Increased production of TNF-alpha may play a role in osteoporosis in cystic
      fibrosis patients.

PMID- 9266916
TI  - Genetic treatment of the haemoglobinopathies: recombinations and new
      combinations.

PMID- 9266917
TI  - Thrombopoietin alone stimulates the early proliferation and survival of human
      erythroid, myeloid and multipotential progenitors in serum-free culture.
AB  - We examined the effects of recombinant human thrombopoietin (TPO, c-Mpl ligand)
      on the proliferation and differentiation of human haemopoietic progenitors other
      than megakaryocytic progenitors using serum-free cultures. TPO alone supported
      the generation of not only megakaryocytic (MK) but also blast cell (blast)
      colonies from cord blood CD34+ cells. Delayed addition of a cytokine cocktail
      (cytokines; interleukin (IL)-3, IL-6, stem cell factor, erythropoietin,
      granulocyte-macrophage colony-stimulating factor, and TPO) to cultures with TPO
      alone on day 7 induced various colonies including granulocyte-macrophage (GM)
      colonies, erythroid bursts (E), granulocyte-erythrocyte-macrophage-megakaryocyte
      (GEMM) colonies. Replating experiments of blast colonies supported by TPO alone
      for culture with cytokines revealed that approximately 60% of the blast colonies
      contained various haemopoietic progenitors. Single cell cultures of clone-sorted
      CD34+ cells indicated that TPO supported the early proliferation and/or survival
      of both primitive and committed haemopoietic progenitors. In serum-free
      suspension cultures, TPO alone significantly stimulated the production of
      progenitors for MK, GM, E and GEMM colonies as well as long-term culture
      initiating cells. These effects were completely abrogated by anti-TPO antibody.
      These results suggest that TPO is an important cytokine in the early
      proliferation of human primitive as well as committed haemopoietic progenitors,
      and in the ex vivo manipulation of human haemopoietic progenitors.

PMID- 9266918
TI  - Thrombopoietin-independent effect of interferon-gamma on the proliferation of
      human megakaryocyte progenitors.
AB  - Flow cytometric study revealed that almost all CD34+ cells in human umbilical
      cord blood expressed interferon-gamma receptor (IFN-gammaR). To clarify the
      precise functional roles of IFN-gammaR in human CD34+ cells, we examined the
      effect of IFN-gamma alone and in combination with various cytokines on the growth
      of haemopoietic progenitor cells in CD34+ cells using a serum-free clonal
      culture. Surprisingly, IFN-gamma alone supported only megakaryocyte (MK) colonies
      in a dose-dependent manner with a plateau level at 1000 U/ml of IFN-gamma. IFN
      gamma at 1000 U/ml induced 10 +/- 1.2 MK colonies from 1 x 10(3) CD34+ cells,
      whereas thrombopoietin (TPO), interleukin (IL)-3, stem cell factor (SCF) or IL-6
      alone induced 22 +/- 4.0, 22 +/- 4.2, 4 +/- 0.6 and 0 MK colonies, respectively.
      The addition of anti-IFN-gamma monoclonal antibody (mAb) to the IFN-gamma culture
      completely abrogated MK colony formation, whereas the mAb had no effect on TPO
      dependent production of MK colonies. In contrast, although anti-TPO polyclonal Ab
      almost completely blocked TPO-dependent MK colony formation, it failed to inhibit
      the generation of MK colonies induced by IFN-gamma, suggesting that the observed
      effect of IFN-gamma on the proliferation of human MK progenitor cells is
      independent of TPO. The addition of IFN-gamma to culture with TPO or SCF
      significantly augmented the development of MK colonies, whereas it did not affect
      IL-3-dependent MK colony formation. Additionally, IFN-gamma induced the increase
      of DNA content of cultured glycoprotein IIb/IIIa-positive megakaryocytes. These
      results suggest that IFN-gamma may have regulatory roles in human
      megakaryocytopoiesis.

PMID- 9266919
TI  - Cytokines active on granulomonopoiesis: release and consumption by human marrow
      myoid [corrected] stromal cells.
AB  - Haemopoiesis is sustained and preferentially committed to granulomonopoiesis by
      myoid [corrected] stromal cells generated by colony-derived cell lines (CDCL).
      Using ELISA and RIA, we studied, in the supernatant of cells from CDCL, the time
      course of interleukins 3 and 6 (IL-3, IL-6), stem cell factor (SCF), granulocyte
      macrophage, granulocyte and macrophage colony stimulating factors (GM-CSF, G-CSF
      and M-CSF), macrophage-inflammatory protein-1alpha (MIP-1alpha) and transforming
      growth factor beta1 (TGF beta1). IL-6, GM-CSF, M-CSF and MIP-1alpha were released
      into the supernatant after medium renewal and, except for M-CSF, addition of IL
      1beta. G-CSF was detected only after addition of IL-1beta. SCF, contained in
      medium, first declined and then increased 24 h after medium renewal. Release of
      TGF beta1 started 24 h after medium renewal and lasted until day 7. IL-3,
      provided by horse serum, declined throughout the 7d of observation. In
      conclusion, stromal cells from CDCL synthesized and released into the
      supernatant. IL-6, GM-CSF, G-CSF, M-CSF and MIP-1alpha after stimulation by seric
      factor(s) and/or IL-1beta. TGF beta1 was synthesized and released without any
      obvious extraneous stimuli. There is no definite argument for synthesis of
      soluble SCF and IL-3. These data support a model where growth factors increase
      shortly after medium renewal, and negative regulators take over at a later time.

PMID- 9266920
TI  - A variant of the EPB3 gene of the anti-Lepore type in hereditary spherocytosis.
AB  - The EPB3 gene encodes band 3 (anion exchanger 1) of the red cell membrane. A
      subset of hereditary spherocytosis (HS) is associated with EPB3 gene mutations
      and band 3 deficiency. We report a large Italian family in which 10 of the 27
      members investigated displayed an autosomal dominant HS. SDS-PAGE revealed a
      reduction in band 3 in the patients. Screening of the Pst I polymorphic site
      confirmed the linkage of HS with the EPB3 gene. Analysis of complementary and
      genomic DNA showed a large additional segment. Nucleotide sequencing disclosed an
      in-frame duplication of 69 nucleotides (nt) including a triplet of intronic
      origin and a genuine exonic duplication of 66 nt. Two CCTGC sequences occurred
      close to one another, one near the intron 12 acceptor splice site (nt -7 to -3),
      and the other within exon 13 (nt 1494-1498). We assumed that the abnormal allele
      arose from an unequal recombination event of the anti-Lepore type between the two
      CCTGC sequences. At the level of the mutated protein, termed band 3 Milano, the
      additional segment (Gln plus duplication of residues 478-499) corresponded to the
      last part of the third transmembrane domain (TM3), the entire second outer loop
      and part of TM4 as it is currently defined in hydropathy analysis. After
      deglycosylation of band 3, only the normal band was detected, supporting the view
      that band 3 Milano is probably not incorporated into the membrane.

PMID- 9266921
TI  - Paroxysmal nocturnal haemoglobinuria due to an 88 bp direct tandem repeat
      insertion in the PIG-A gene.
AB  - Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired stem cell abnormality
      which frequently develops in patients with aplastic anaemia. The disease is due
      to somatic mutations in the PIG-A gene, and a variety of mutations have been
      reported. The majority are point mutations, or small insertions and deletions
      resulting in a frameshift. Previous insertions reported have all been within the
      range of 1-10 bp. We describe here a patient with PNH due to a large insertion of
      88 bp; DNA sequencing showed this to be a tandem repeat of PIG-A sequences. The
      same mutation could be found in granulocytes and lymphocytes, indicating a
      pluripotent stem cell origin.

PMID- 9266922
TI  - The effect of intravenous iron on the reticulocyte response to recombinant human
      erythropoietin.
AB  - We studied the effect of intravenous (i.v.) administration of 200 mg of iron
      sucrose following an i.v. bolus injection of recombinant human erythropoietin (r
      HuEPO; 300 U/kg body weight) in seven subjects and compared it with seven
      subjects treated with r-HuEPO alone. Reticulocytes, serum erythropoietin (EPO)
      and ferritin levels were studied at baseline and daily for the following 8 d. Use
      of i.v. iron abolished the marked reduction in serum ferritin observed with r
      HuEPO administration. Although the total number of reticulocytes was not affected
      by i.v. iron administration, the reticulocyte Hb content and retHb (a measure in
      g/l of the Hb contained in all reticulocytes) were increased in the i.v. iron/r
      HuEPO group compared with the group who received r-HuEPO alone. Therefore i.v.
      iron significantly potentiates the haemopoietic response to r-HuEPO in normal
      subjects.

PMID- 9266923
TI  - Reduced interferon-alpha production by Epstein-Barr virus transformed B
      lymphoblastoid cell lines and lectin-stimulated lymphocytes in congenital
      dyserythropoietic anaemia type I.
AB  - The concentrations of interferon-alpha (IFN-alpha) in supernatants from cultures
      of Epstein-Barr virus (EBV) transformed B-lymphoblastoid cell lines derived from
      seven patients with congenital dyserythropoietic anaemia (CDA) type I were below
      the 95% confidence limits for those derived from six healthy subjects. In
      contrast, the concentrations of IFN-alpha in supernatants from cultures of EBV
      transformed lymphoblastoid cell lines derived from four patients with other types
      of CDA and four patients with hereditary sideroblastic anaemia were normal.
      Supernatants from cultures of peripheral blood lymphocytes stimulated with
      phytohaemagglutinin or pokeweed mitogen contained less IFN-alpha when the cells
      were derived from patients with CDA type I than when derived from healthy
      subjects. Since patients with CDA type I show a substantial haematological
      response to treatment with IFN-alpha, the data suggest that impaired IFN-alpha
      production may be an important pathogenetic mechanism in CDA type I.

PMID- 9266924
TI  - Immunophenotypic and ultrastructural study in peripheral blood neutrophil
      granulocytes following bone marrow transplantation.
AB  - Neutrophil studies after bone marrow transplantation (BMT) describe chemotactic
      and phagocytotic alterations and dyshaemopoiesis. Neutrophil granulocytes (NG) in
      peripheral blood after BMT were analysed in 28 patients. 14 patients (six
      receiving GM-CSF) underwent autologous BMT and 14 underwent allogeneic BMT.
      Immunophenotypic and electron microscopic studies were performed during post-BMT
      granulopoietic regeneration. Results were compared with NG from 15 healthy bone
      marrow donors (control group A) and from six patients receiving intensive
      chemotherapy before autologous BMT (control group B). A significant increase in
      CD15 and a decrease in 8C7 antigen expression was observed in peripheral blood NG
      from BMT patients compared with controls A. MPO-7 in NG after BMT did not differ
      from control group A. Autologous BMT patients showed a lower percentage of NG
      expressing 13F6, 31D8 and CD16 (Leu 11a) than allogeneic BMT patients, and a
      significant decrease in 8C7 antigen expression compared with patients receiving
      intensive chemotherapy. Ultrastructurally, a marked decrease of azurophilic
      granules was observed in NG from BMT patients compared with control groups A and
      B. These data indicate that repopulation after BMT was made by phenotypically
      less mature NG with dysgranulopoietic features. Differences between autologous
      and allogeneic BMT patients may be partly related to GM-CSF usage. In conclusion,
      NG present immunophenotypic and ultrastructural changes after BMT which may be
      involved in abnormal NG response against bacterial infections, although further
      investigation is needed.

PMID- 9266925
TI  - Granulocytopenia in Cohen syndrome.
AB  - Cohen syndrome is an autosomal recessive disorder characterized by mental
      retardation, microcephalia and typical craniofacial features, myopia and
      chorioretinal dystrophy. As some patients were reported to have leucopenia, we
      collected the haematological data of 26 Finnish Cohen patients. They all had
      experienced periods of isolated granulocytopenia from an early age.
      Granulocytopenia was mild to moderate, non-cyclic and never fatal. Most patients
      suffered from prolonged or repeated gingival or skin infections. We restudied 16
      patients. Bone marrow examination revealed in all patients a normo- or
      hypercellular marrow, with a left-shifted granulopoiesis in 8/16 patients. The
      response to adrenaline stimulation was subnormal in 12/14 and to hydrocortisone
      in 8/16 patients, but administration of rhG-CSF caused granulocytosis in the
      three patients studied. No bone marrow malignancies were seen.

PMID- 9266926
TI  - The eosinophil granule proteins in serum, but not the oxidative metabolism of the
      blood eosinophils, are increased in cancer.
AB  - The eosinophil activity in patients with renal cell adenocarcinoma during
      treatment with interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) was reduced
      when measured as zymosan-induced lucigenin-enhanced chemiluminescence (CL).
      Eosinophil cationic protein (ECP), eosinophil peroxidase (EPO) and eosinophil
      protein-X (EPX) were significantly elevated before and during treatment (P<0.001)
      when compared with the controls. ECP and EPO were unaffected by the treatment
      whereas it induced an increased EPX level compared with values measured before
      treatment (P<0.05). The propensity of eosinophils to secrete their granule
      proteins may reflect the fact that eosinophils in cancer patients have an
      enhanced capacity to kill cancer cells.

PMID- 9266927
TI  - Thrombocytopenia following liver transplantation is associated with platelet
      consumption and thrombin generation.
AB  - Thrombocytopenia frequently occurs immediately after orthotopic liver
      transplantation. We have investigated the cause of this phenomenon in a cohort of
      45 consecutive liver transplant recipients. The median preoperative platelet
      count (range) of 129 x 10(9)/l (14-719) fell to 56 x 10(9)/l (23-334) by the
      fourth postoperative day. The median preoperative reticulated platelet percentage
      (range) of 6.7% (2.2-23.9) increased to 16.4% (4.6-40.8) on day 7. There was a
      significant rise in prothrombin fragment F1.2 by the first postoperative day
      which was followed by rises in fibrinogen and fibrin degradation products. There
      was no increase in platelet-associated immunoglobulin or markers of endothelial
      activation. We conclude that there is an increased rate of platelet consumption
      associated with thrombin generation that reflects the magnitude of liver
      transplant surgery.

PMID- 9266928
TI  - The effect of cardiopulmonary bypass on circulating megakaryocytes.
AB  - Megakaryocytes (Mks) are found in the lungs and the blood stream as well as in
      the bone marrow. We modified a whole blood filtration method for Mks by
      immunostaining for CD61 using biotin streptavidin, and used this technique to
      study Mks and their morphology in the central venous and arterial circulations
      before, during and after cardiopulmonary bypass (CPB) in haematologically normal
      patients undergoing routine cardiac surgery. Blood samples were taken immediately
      after the insertion of central venous (V) and arterial (A) catheters and after
      thoracotomy, immediately before bypass. Further samples were taken after 60-90
      min on-CPB and 180-240 min post-bypass. In comparison with the steady state
      before bypass, circulating Mk levels in blood on bypass increased dramatically,
      from (V) 10.93 +/- 3.94/ml (mean +/- SD) to 36.48 +/- 11.52/ml and from (A) 8.37
      +/- 4.39/ml to 38.65 +/- 20.68/ml. This effect was still present, to a lesser
      extent, 180-240 min post-bypass. Circulating levels of Mks were consistently
      lower in the arterial circulation than in the venous circulation off bypass, but
      levels in the two circulations were comparable during CPB, confirming previous
      suggestions that the lungs are net removers of Mks from the circulation. Type 4
      Mks, the largest and most normal morphologically, were rarely seen in arterial
      blood, but increased significantly during CPB, indicating that the lungs
      selectively remove large Mks. The lungs appear to play an active role in the
      regulation of Mk levels. This is lost during CPB and despite the extracorporeal
      40 microm arterial line filter, large Mks enter the systemic circulation. More
      effective extracorporeal filtration of large Mks might reduce the neurological
      impairment seen in some patients who have undergone CPB.

PMID- 9266929
TI  - Quantitation of platelet-specific autoantibodies in platelet eluates of ITP
      patients measured by a novel ELISA using the purified glycoprotein complexes
      GPIIb/IIIa and GPIb/IX as antigens.
AB  - Immune thrombocytopenic purpura (ITP) is a disorder caused by anti-platelet
      autoantibodies (Ab), most of which are directed against epitopes on platelet
      membrane glycoprotein complexes GPIIb/IIIa and GPIb/IX. To detect platelet Ab,
      reliable techniques, such as MAIPA or immunobead assay, have been developed. They
      all achieve their selective specificity by the use of monoclonal antibodies
      (MoAb) against defined glycoproteins of the platelet membrane. In order to
      determine the most frequent Ab-specificities, a novel enzyme-linked immunosorbent
      assay, named platelet-glycoprotein-ELISA (P-GP-ELISA), has been developed. It
      uses purified GPIIb/IIIa and GPIb/IX complexes, respectively, as antigens and
      enables determination of platelet-associated as well as circulating Ab (IgG,
      IgM). MoAbs are not required and therefore there is no risk of competition
      between MoAb and Ab. Levels of Ab in patients with the clinical diagnosis of an
      idiopathic thrombocytopenic purpura were analysed. 92.7% (76/82) platelet eluates
      with significantly increased levels of Ab against at least one of the
      glycoproteins were found, whereas no sample from healthy volunteers (0/37) gave a
      positive result, pointing to a high sensitivity and specificity of the test
      system. Since its application is also easy and quick, P-GP-ELISA should
      facilitate detection of Ab against platelet membrane proteins in routine
      determinations.

PMID- 9266930
TI  - Anti-platelet antibodies in patients with systemic lupus erythematosus and the
      primary antiphospholipid antibody syndrome: their relationship with the observed
      thrombocytopenia.
AB  - The role of antiphospholipid antibodies in the pathogenesis of the
      thrombocytopenia observed during primary antiphospholipid antibody syndrome
      (APAS) and systemic lupus erythematosus (SLE) remains controversial. We have used
      the MAIPA test to examine the frequency and specificity of anti-platelet
      antibodies directed against the major platelet membrane glycoproteins (GP IIb
      IIIa, GP Ib-IX, GP Ia-IIa and GP IV) in patients where SLE and APAS were
      associated or not with thrombocytopenia. Results were compared with a series of
      26 ITP patients, 46% of whom were shown to possess anti-platelet antibodies
      directed against one or more of the platelet surface glycoproteins. When APAS was
      associated with thrombocytopenia, 7/10 patients possessed antibodies against GP
      IIb-IIIa and/or GP Ib-IX. For SLE patients with thrombocytopenia, 6/10 patients
      were shown to have antiplatelet antibodies against GP IIb-IIIa, GP Ib-IX or GP
      IV. In contrast, for APAS (n=11) and SLE patients (n=11) without
      thrombocytopenia, only one patient had an antibody directed against GP IIb-IIIa
      and one patient had an antibody to GP IV. Our results suggest that antibodies
      directed against major platelet membrane glycoproteins may play a role in the
      thrombocytopenia that is seen during SLE and APAS.

PMID- 9266931
TI  - Lupus anticoagulants: strong association with the major histocompatibility
      complex class II and platelet antibodies.
AB  - A relationship between the presence of platelet autoantibodies and major
      histocompatibilty complex class II alleles was determined in 27 patients with
      lupus anticoagulants. Twenty-two patients had a primary antiphospholipid
      syndrome' and five patients had lupus erythematosus (SLE). Platelet antibodies
      against the platelet glycoproteins (GP) IIb/IIIa were detectable in 20 patients.
      Anti-GPIb/IX or -GPIV antibodies were detectable only in patients with anti
      GPIIb/IIIa antibodies. An increased frequency of HLA-DQB1*06 was demonstrable in
      the total patient population. The association between the lupus anticoagulants
      and HLA-DQB1*06 was even stronger if patients also had detectable platelet
      antibodies. This association was also seen if patients with a history of
      thromboembolic disease were considered separately. However, within the patient
      population there was no difference between frequencies of HLA alleles detectable
      platelet antibodies.

PMID- 9266932
TI  - Structural analysis of a missense mutation (Val414Phe) in the catalytic core
      domain of the factor XIII(A) subunit.
AB  - Molecular analysis has been performed on a Malaysian patient with a severe
      bleeding disorder due to factor XIII(A) subunit deficiency. Total mRNA was
      isolated from the patient's leucocytes and four overlapping segments
      corresponding to the entire coding region of the A subunit cDNA were amplified by
      RT-PCR. The cDNA segments amplified efficiently and were of expected size. Direct
      sequencing of the complete reading frame revealed a single homozygous base change
      (nt 1327G-T) in exon 10 corresponding to a missense mutation, Val414Phe, in the
      catalytic core domain of the A subunit monomer. The mutation eliminates a BsaJ1
      restriction site and family screening showed that both parents were heterozygous
      for the defect. The base substitution was absent in 55 normal individuals. Val414
      is a highly conserved residue in the calcium-dependent transglutaminase enzyme
      family. Computer modelling based on 3D crystallographic data predicts that the
      bulky aromatic side chain of the substituted phenylalanine residue distorts
      protein folding and destabilizes the molecule. In addition, conformation changes
      in the adjacent catalytic and calcium binding regions of the A subunit are likely
      to impair the enzymatic activity of any protein synthesized.

PMID- 9266933
TI  - The prothrombin gene G20210A variant: prevalence in a U.K. anticoagulant clinic
      population.
AB  - We have investigated the prevalence of a recently reported genetic variation in
      the prothrombin gene (G20210A) in patients with an objectively confirmed history
      of venous thrombosis, 12/219 patients (5.5%) were found to be heterozygous
      carriers of the 20210A allele. The incidence of the 20210A allele in a group of
      164 healthy controls was 1.2% (allele frequency 0.61%, 95% CI 0.08-2.19). When
      patients with a known alternative hereditary risk factor for venous thrombosis
      (factor V Leiden mutation or deficiency of antithrombin, protein C or protein S)
      were excluded, the G20210A variant was found to increase the risk for venous
      thrombosis by approximately 5-fold (odds ratio 5.4, 95% CI 1.16-25.0). This
      prothrombin gene sequence variation adds further to the list of recognized
      genetic risk factors for thrombophilia.

PMID- 9266934
TI  - Specificity and sensitivity of RHD genotyping methods by PCR-based DNA
      amplification.
AB  - We have compared the sensitivity and specificity of four PCR methods of RHD gene
      detection using different sets of primers located in the regions of highest
      divergence between the RHD and RHCE genes, notably exon 10 (method I), exon 7
      (method II), exon 4 (method III) and intron 4 (method IV). Methods I-III were the
      most sensitive and gave a detectable signal with D-pos/D-neg mixtures containing
      only 0.001% D-positive cells. Moreover, method II could detect the equivalent DNA
      amount present in only three nucleated cells in the assay without hybridization
      of PCR products, whereas the sensitivity of the other methods was 10-50 times
      less. Investigation of D variants indicated that false-negative results were
      obtained with method II (D(IVb) variant), method III (D(VI) and DFR variants) and
      method IV (D(VI) variants), but not method I. Weak D (D(u)) was correctly
      detected as D-positive by all methods, but most cases of Rh(null) appeared as
      false-positives, as they carry normal RH genes that are not phenotypically
      expressed. Some false-positive results were obtained with method I in a few
      Caucasian DNA samples serotyped as RhD-neg but carrying a C- or E-allele, whereas
      a high incidence of false-positives was found among non-Caucasian Rh-negative
      samples by all methods. In the Caucasian population, however, we found a full
      correlation between the predicted genotype and observed phenotype at birth of 92
      infants. Although we routinely use the four methods for RHD genotyping, a PCR
      strategy based on at least two methods is recommended.

PMID- 9266935
TI  - A human monoclonal anti-D antibody which detects a nonconformation-dependent
      epitope on the RhD protein by immunoblot.
AB  - We describe the first human monoclonal anti-D (LOR-15C9) which reacts with a D
      specific motif exposed either on a native form on intact D-positive red cells or
      on a denatured form of the RhD protein (33 kD), and detected by immunoblotting.
      LOR-15C9 was able to precipitate RhD but not RhcE proteins produced by in vitro
      transcription-translation assays. The reactivity of the antibody, using panels of
      red cells with various partial D phenotypes known to lack some D epitopes and
      corresponding in RHD gene variants, suggested that LOR-15C9 reactivity depends on
      the portion of the RhD polypeptide encoded by the exon 7 (amino acids 314-358).
      These findings correlate well with the reactivity of LOR-15C9 with erythrocytes
      of some nonhuman primates (D(gor)-positive gorillas), but not of chimpanzee and
      Old or New World monkeys. In membrane proteins from partial D(VI) red cells, LOR
      15C9 detected two proteins of molecular weight 33 and 21 kD: the presence of the
      latter was specific for category D(VI) and presumably represented the product of
      an alternatively spliced RHD(VI) transcript in these cells. This is consistent
      with the finding that LOR-15C9 can precipitate a shortened D protein mutant
      resulting from in vitro transcription-translation and lacking amino-acids 163-313
      encoded by exons 4-6. In addition, a 21 kD band polypeptide was detected by
      immunoblot in all red cell samples but D--, using a rabbit anti-Rh polypeptide
      antibody (MPC8) raised against the C-terminal domain of Rh proteins. This 21 kD
      polypeptide most probably results from the translation of an alternatively
      spliced RHCE gene transcript. This study demonstrates that LOR-15C9 detects an
      epitope on the RhD protein that is independent of the membrane environment, and
      therefore could be a useful tool for the study of RhD polypeptides.

PMID- 9266936
TI  - The significance of minimal residual disease in hairy cell leukaemia treated with
      deoxycoformycin: a long-term follow-up study.
AB  - We investigated the clinical significance and long-term follow-up of detecting
      minimal residual disease (MRD) in hairy cell leukaemia (HCL) in complete
      remission (CR) after treatment with deoxycoformycin (DCF). MRD was assessed in 23
      patients by immunophenotyping peripheral blood and bone marrow frozen sections
      using a panel of antibodies, CD11c, CD25, CD103 and HC2, which detect hairy
      cells. 31 cases with active HCL were used as controls. 10/23 patients (43%) had
      MRD in bone marrow (seven), blood (one) or both sites (two) which was not
      detected on haematoxylin-eosin bone marrow sections nor by immunohistochemistry
      on paraffin sections in six cases tested. Sequential studies in four cases did
      not show changes in the amount of MRD. At a median follow-up of 72 months (range
      15-108), 5/23 (22%) patients have relapsed with a median time of 59 months (range
      15-105). MRD was detected in three of the five patients who relapsed. In the two
      patients with negative MRD, one relapsed with an abdominal mass and the other was
      a late relapse at 84 months. MRD was also documented in 7/18 patients who
      continued in clinical CR for a median of 80 months (range 63-98). There were no
      statistical differences in disease-free survival between MRD+ and MRD- patients
      (P = 0.8). Our findings indicate that relapse after long-term remission achieved
      with DCF cannot be predicted when MRD is detected by sensitive methods. A search
      for other parameters such as proliferative rate of the residual cells or chest
      and abdominal CT scan might identify patients with a higher probability of
      disease recurrence.

PMID- 9266937
TI  - Increased frequency of somatic mutations at glycophorin A loci in patients with
      aplastic anaemia, myelodysplastic syndrome and paroxysmal nocturnal
      haemoglobinuria.
AB  - Paroxysmal nocturnal haemoglobinuria (PNH), aplastic anaemia (AA) and
      myelodysplastic syndrome (MDS) are haemopoietic stem cell disorders. These
      disorders have some features in common, and a percentage of cases progress to
      acute leukaemia. We speculated that changes in gene stability are involved in the
      pathogenesis of these haemopoietic stem cell disorders. Therefore we investigated
      in vivo mutation frequencies in these disorders by erythrocyte glycophorin A
      (GPA) mutation assay. The assay enumerates NO or NN variant cells in 106
      erythrocytes of the MN type using a flowcytometric technique. Patients undergoing
      chemotherapy known to be at risk of hypermutageneity were also studied. Events
      exceeding the 95th percentile of healthy donors (> or = 32 and 34 events,
      respectively for NO and NN variants) were defined as abnormal. Abnormal events in
      the NO variants were found in three out of seven patients undergoing
      chemotherapy, two out of nine patients with AA, two out of seven patients with
      MDS, and four out of nine patients with PNH. Abnormal events in the NN variants
      were found in three out of seven patients undergoing chemotherapy, two out of
      nine patients with AA, one out of seven patients with MDS, and two out of nine
      patients with PNH. These results suggest that not only PIG-A, but also other
      genes including the GPA gene, are hypermutable in haemopoietic stem cell
      disorders, and that mutagenic pressure and/or gene instability can contribute to
      the pathogenesis of these disorders.

PMID- 9266938
TI  - Alterations of p53 and Rb genes in a novel human GM-CSF-dependent myeloid cell
      line (OHN-GM) established from therapy-related leukaemia.
AB  - A novel GM-CSF-dependent myeloid cell line, OHN-GM, was established from a
      patient who developed acute myelogenous leukaemia (AML) as a consequence of
      myelodysplastic syndrome (MDS). As the patient had previously received cytotoxic
      chemotherapy for Hodgkin's disease, the MDS and AML were probably related to such
      therapy. Sequential karyotypic analysis established a del(5q) as the initial
      cytogenetic abnormality. Additional alterations, including t(10;13)(q24;q14), had
      developed subsequently during disease progression. Southern blot analysis of OHN
      GM cells suggested deletion of one allele of the IRF-1 gene, although no aberrant
      transcripts were detected. Fluorescence in situ hybridization analysis revealed
      the deletion of the Rb gene due to the t(10;13)(q24;q14) translocation, and
      Western blot analysis demonstrated the absence of Rb protein in OHN-GM cells.
      Finally, the OHN-GM cells exhibited two missense point mutations in highly
      conserved regions of the p53 gene. These observations suggest that a multistep
      process, involving alterations of Rb and p53 genes, may have contributed to the
      patient's disease development and progression. To our knowledge, OHN-GM is the
      first cell line derived from a therapy-related AML. These cells may aid the
      investigation of leukaemogenesis as well as the biology of secondary leukaemia.

PMID- 9266939
TI  - Establishment of a novel human myeloid leukaemia cell line (HNT-34) with
      t(3;3)(q21;q26), t(9;22)(q34;q11) and the expression of EVI1 gene, P210 and P190
      BCR/ABL chimaeric transcripts from a patient with AML after MDS with 3q21q26
      syndrome.
AB  - A novel human myeloid leukaemia cell line (HNT-34) was established from the
      peripheral blood of a 45-year-old female patient with acute myelogenous leukaemia
      (AML) transformed from chronic myelomonocytic leukaemia (CMMoL) with 3q21q26
      syndrome. Morphologically, the HNT-34 cells were undifferentiated blasts which
      were negative for myeloperoxidase. The HNT-34 cells were positive for CD4, CD13,
      CD33 and CD34, but negative for CD41a and CD42b. The cells actively proliferated
      in suspension with a doubling time of 26-27h in the absence of any growth
      factors. Neither proliferative advantage nor differentiation was observed with
      the addition of G-CSE GM-CSF, IL-3, TPO, DMSO or PMA. Cytogenetic analysis showed
      46,XX. t(3;3)(q21;q26), t(9;22)(q34;q11),20q-. Molecular analysis showed
      expression of EVI1 gene, P210 and P190 BCR/ABL chimaeric transcripts. The
      chromosomal breakpoint at 3q26 of HNT-34 cell line was located to approximately
      200 kb 5' of FIM3 locus and more upstream of the MDS1. which is the same region
      as that of somatic cell hybrid line H10C. The breakpoint at 3q21 was located
      within the 390 kb centromeric from the breakpoint cluster region. These results
      suggest that the HNT-34 cell line may be a useful tool for the elucidation of the
      mechanisms of leukaemogenesis which involve the 3q21q26 syndrome and Ph1
      chromosome.

PMID- 9266940
TI  - Complementarity determining region-III is a useful molecular marker for the
      evaluation of minimal residual disease in mantle cell lymphoma.
AB  - Bone marrow (BM) and peripheral blood (PB) involvement in 10 patients with mantle
      cell lymphoma (MCL) was analysed by a polymerase chain reaction (PCR)-mediated
      RNase protection assay. The complementarity determining regions (CDR)-III of all
      10 MCLs examined was amplified efficiently with consensus V(H) and J(H) primers
      by PCR. and BM and/or PB involvement was evaluated by RNase protection assay in
      all 10 patients examined. Our assay showed BM and/or PB of the entire group to
      have neoplastic cells at presentation, despite the fact that eight patients were
      found to have BM and/or PB involvement on the basis of morphological examination
      and/or surface marker analysis. We also examined minimal residual disease (MRD)
      after conventional chemotherapy, and detected MRD in a patient in complete
      remission (CR). Although previous studies have shown that t(11;14) breakpoint
      amplification by PCR was only applicable to about 30-40% of cases, the present
      study indicates that CDR-III is a useful molecular marker and the PCR-mediated
      RNase protection assay is a good tool for the evaluation of MRD in MCL. It is
      suggested that BM and PB of MCL patients are quite frequently involved at
      presentation and even after conventional chemotherapy at the molecular level.

PMID- 9266941
TI  - Interleukin-4 prevents spontaneous in-vitro apoptosis in chronic lymphatic
      leukaemia but sensitizes B-CLL cells to melphalan cytotoxicity.
AB  - The effect of IL4 on cell viability, cell growth, apoptotic fraction, melphalan
      induced cytotoxicity and the degree of interstrand DNA cross-linking after
      alkylating agent exposure was investigated in peripheral blood B-cell chronic
      lymphocytic leukaemia (B-CLL) cells obtained from 10 patients suffering from
      chronic lymphocytic leukaemia and in B lymphocytes from five normal individuals.
      The addition of IL4 to culture medium maintained in-vitro viability and decreased
      spontaneous in-vitro apoptosis in both B-CLL cells and normal peripheral blood B
      lymphocytes. IL4 did not, however, stimulate proliferation of either cell type.
      IL4 sensitized alkylator-resistant B-CLL cells to the cytotoxic effects of
      melphalan (L-phenylalanine mustard) but had no influence on melphalan-induced
      cytotoxicity against normal B lymphocytes. The enhanced cytotoxicity against B
      CLL cells was accompanied by an increase in the amount of interstrand-DNA cross
      linking in these cells following short-term exposure to melphalan.

PMID- 9266942
TI  - Hypodiploidy and 22q11 rearrangements at diagnosis are associated with poor
      prognosis in patients with multiple myeloma.
AB  - Our aim was to evaluate the clinical use of cytogenetic analysis as a prognostic
      factor in the outcome of newly diagnosed multiple myeloma (MM) patients. The
      present series includes 111 newly diagnosed MM patients treated with one of three
      standard-dose regimens or autologous transplantation over an 8-year time
      interval. As expected, the presence of an abnormal karyotype (39% of patients)
      correlated with poor prognosis (progression rate 63% v 47%, P = 0.042), shorter
      event-free (EFS, P = 0.014) and overall (OS, P = 0.005) survival. Two distinct
      cytogenetic abnormalities were the most significant variables that influenced EFS
      and OS in the univariate analysis. The presence of hypodiploid karyotypes or
      rearrangements of band 22q11 were associated with higher progression rate (P =
      0.001) and shorter EFS (P < 0.024) and OS (P < 0.004). The median EFS and OS for
      patients with hypodiploidy was 4 and 7 months respectively. Multivariate analysis
      showed that absence of hypodiploidy was the most favourable prognostic variable
      for OS (P = 0.022) followed by stage < or = IIA, serum calcium < or = 2875
      micromol/l, and absence of abnormalities 22q. The data suggest that the presence
      of hypodiploid karyotypes and rearrangements on 22q11 band show a higher
      progression rate and shorter survival in MM patients.

PMID- 9266943
TI  - Assessment of intracellular TAP-1 and TAP-2 in conjunction with surface MHC class
      I in plasma cells from patients with multiple myeloma.
AB  - Immunotherapy involving cytotoxic T lymphocytes (CTLs) is an attractive
      alternative for treatment of various malignancies, including multiple myeloma.
      For tumour cells to be recognized and killed by CTLs they must express cell
      surface major histocompatibility complex (MHC) class I molecules and the
      transporter associated with antigen processing (TAP). However, loss of MHC class
      I and the TAP protein are common among several types of solid tumours. This study
      assessed the expression of TAP protein (by intracellular flow cytometry) and cell
      surface MHC class I molecules in three human myeloma cell lines as well as the
      plasma cell population (CD38+ bright) in bone marrow specimens from 13 multiple
      myeloma patients. In all of the patients, 100% of the plasma cell population
      expressed both the TAP subunits and cell surface MHC class I molecules, but at
      varying intensities. Both TAP and MHC class I were also expressed in the three
      myeloma lines. Additionally, the function of the antigen transport machinery was
      evaluated by a peptide transporter assay in the three myeloma lines. TAP
      transporter activity was readily detectable in two out of three myeloma lines,
      whereas the diminished activity in the third cell line was completely restored by
      co-culturing with recombinant interferon-gamma (rIFN-gamma).

PMID- 9266944
TI  - Therapeutic leukapheresis in hyperleucocytic leukaemias: lack of correlation
      between degree of cytoreduction and early mortality rate.
AB  - The clinical and laboratory data of 48 leukapheresis-treated patients with
      hyperleucocytic leukaemia (HL) was reviewed to assess the correlation between the
      degree of leucoreduction and early mortality. Leukapheresis resulted in > 50%
      leucoreductions and postapheresis WBC counts < 100 x 10(9)/l in most patients
      (64.5%). Patients presenting with neurological, respiratory or renal
      complications had higher early mortality rates than patients without such
      complications, despite similar initial WBC counts and comparable leucoreductions.
      Thus, in these patients, more efficient leucoreduction was not associated with
      improved early survival.

PMID- 9266945
TI  - Central nervous system relapse in acute promyelocytic leukaemia in patients
      treated with all-trans retinoic acid.
AB  - All-trans retinoic acid (ATRA) is currently recommended as standard treatment for
      acute promyelocytic leukaemia (APL). However, there has been increasing concern
      that ATRA is associated with unusual sites of relapse. We present three cases of
      APL previously treated with ATRA who ultimately relapsed within the central
      nervous system (CNS) and hypothesize that, by up-regulating intercellular
      adhesion molecules, ATRA may facilitate the passage of malignant promyelocytes
      across the blood-brain barrier.

PMID- 9266946
TI  - PML/RAR alpha rearrangement in acute promyelocytic leukaemia with t(1;17)
      elucidated using fluorescence in situ hybridization.
AB  - Acute promyelocytic leukaemia (APL) is characterized by t(15;17)(q22;q21) which
      results in the formation of two chimaeric genes, PML/RAR alpha and RAR alpha/PML,
      thought to play a role in leukaemogenesis. We report a case of a patient with APL
      apparently lacking the t(15;17) but with t(1;17) translocation identified by
      fluorescence in situ hybridization (FISH). Chromosome 15 seemed intact but
      PML/RAR alpha fusion transcript was detected by molecular analysis. The patient
      achieved complete remission with all-trans retinoic acid treatment associated
      with chemotherapy. This case illustrates the usefulness of combined cytogenetics,
      FISH and molecular biology in cases with no evident t(15;17) to predict response
      to treatment.

PMID- 9266947
TI  - CD3+ CD8+ CD56- clonal large granular lymphocyte leukaemia and HIV infection.
AB  - High-grade malignant lymphomas associated with HIV infection are usually derived
      from B lymphocytes. Although a broad spectrum of T-cell-derived malignancies has
      been described, no case of monoclonal T large granular lymphocyte leukaemia has
      been reported to date. We report a case of clonal T-LGL (CD3+, CD4-, CD8+, CD56-,
      CD57+) in an HIV-infected. HTLV1/2-negative individual. Large granular
      lymphocytes are thought to represent activated cytotoxic T lymphocytes. HIV
      infection, as previously reported for HTLV1/2, may represent a pathway of antigen
      activation and lead to clonal expansion of T large granular lymphocytes.

PMID- 9266948
TI  - Frequent involvement of chromosomes 1, 3, 7 and 8 in splenic marginal zone B-cell
      lymphoma.
AB  - We have studied 19 cases of splenic marginal zone B-cell lymphoma (SMZBCL)
      combining cytological features, conventional cytogenetics, and in situ
      hybridization (ISH) techniques. A clonal chromosome abnormality was found in
      11/19 patients (58%). The more frequent recurrent abnormalities were: del(3), del
      (7q), and involvement of chromosomes 1, 3, 7 and 8. No patient showed the
      translocation t(11;14)(q13;q32). An outstanding finding was the low incidence of
      trisomy 3 (36%) compared to patients with MALT lymphoma. These findings support
      the interpretation that SMZBCL is a distinct lymphoproliferative disorder.

PMID- 9266949
TI  - High serum levels of CA125 and interleukin-6 in a patient with Ki-1 lymphoma.
AB  - We report a 53-year-old-man with an aggressive Ki-1 lymphoma who had high serum
      CA125, a marker protein of the epithelial ovarian cancer, and interleukin-6 (IL
      6) concentrations. Both CA125 and IL-6 levels decreased after chemotherapy and
      elevated with disease progression. The patient's lymphoma cells obtained before
      chemotherapy grew continuously in vitro, were IL-6 dependent and were found to
      secrete CA125 in culture medium. These results indicate that CA125 can be
      secreted by Ki-1 lymphoma cells and IL-6 may promote the growth of Ki-1 lymphoma
      cells.

PMID- 9266950
TI  - Short- and long-term follow-up of thyroid dysfunction after allogeneic bone
      marrow transplantation without the use of preparative total body irradiation.
AB  - We studied the incidence and potential prognostic value of thyroid abnormalities
      after allogeneic bone marrow transplantation (BMT) without total body irradiation
      (TBI) conditioning. 77 consecutive patients who received a chemotherapy-alone
      based conditioning regimen pretransplant were included. Free serum thyroxine
      (FT4), free serum triiodothyronine (FT3) and serum thyrotropin (TSH) levels were
      assayed before and 3 and 14 months after BMT. Patients were classified in three
      categories: normal thyroid profile if FT3 and FT4 were within the normal range
      and TSH was normal or low, peripheral thyroid insufficiency (PTI) if TSH was >4
      mIU/l, or an 'euthyroid sick syndrome' (ETS) if FT3 and/or FT4 were low and TSH
      was normal or low. The incidence of thyroid dysfunction at 3 months was 57%, and
      29% at 14 months. This was mostly due to the occurrence of ETS which was more
      frequent at 3 months (48%, 29/61) than at 14 months (19%, 9/48). Furthermore, at
      3 months, survival was significantly lower in the ETS group (34.5%) than in the
      euthyroid group (96.2%), or in the PTI group (83.3%) (P < 0.0001). PTI was
      observed even in the absence of TBI in 11 patients (14%) and was equally
      distributed at 3 months (n = 6) and 14 months (n = 5). In conclusion, thyroid
      dysfunction is not a rare complication even without pretransplant TBI
      conditioning regimen. Hypothyroidism prevalence was 10%, and ETS, which was more
      frequently observed, displayed a dismal predictive value at 3 months.

PMID- 9266951
TI  - Detection of BCR/ABL RNA transcripts using the polymerase chain reaction is
      highly predictive for relapse in patients transplanted with unrelated marrow
      grafts for chronic myelogenous leukaemia.
AB  - Relapse after allogeneic bone marrow transplantation (BMT) for chronic
      myelogenous leukaemia (CML) is thought to result from residual leukaemia cells
      which survive the intensive conditioning regimen and are not eradicated by donor
      derived immune effector cells capable of mediating a graft-versus-leukaemia (GVL)
      effect. Early relapse can be detected using highly sensitive assays such as the
      polymerase chain reaction (PCR) which have been shown to have predictive value
      for subsequent relapse in selected patient populations. The validity of PCR for
      predicting CML relapse in unrelated marrow transplant recipients where the GVL
      effect appears to be augmented due to increased HLA disparity between donor and
      recipient, however, has not been well defined. In this study we assessed the
      prognostic value of PCR in a cohort of 52 patients transplanted with T-cell
      depleted unrelated marrow grafts for CML. The actual probability of relapse at 3
      years was 71% in patients with at least one positive assay versus 6% in patients
      with no positive assays post-transplant. Patients with one or more positive
      assays at any time post-transplant had a 56-fold increased risk of relapse which
      was significantly higher (P=0.0002) than that observed in patients who remained
      persistently PCR negative. Moreover, PCR detected relapse a median of 5 months
      earlier than cytogenetic analysis in a subgroup of patients in whom concurrent
      sampling had been performed. These data validate the use of PCR as a prognostic
      test in this patient population and may help to identify a cohort of patients to
      be considered as candidates for pre-emptive adoptive immunotherapy.

PMID- 9266952
TI  - Ex vivo cytokine expansion of peripheral blood 5-fluorouracil-treated CD34
      positive chronic myeloid leukaemia cells increases the selection of Ph-negative
      cells.
AB  - It has been shown that normal early progenitor or stem cells persist in the blood
      and bone marrow of patients with Philadelphia chromosome (Ph)-positive chronic
      myeloid leukaemia (CML); it is also known that normal haemopoietic progenitors
      can be expanded ex vivo in the presence of various cytokine combinations. The
      selection of normal (Ph-negative) progenitor cells from CML patients would
      potentially be of considerable clinical value for ex vivo purging and autologous
      transplantation. To obtain these cells. CD34-positive (progenitor) cells from the
      peripheral blood (PB) of CML patients were pretreated with 5-fluorouracil (5FU)
      (5 microg/ml) to suppress Ph-positive cells and then grown in suspension culture
      for 7 d with a combination of cytokines. We compared two combinations of
      cytokines: interleukin-1alpha (IL1alpha) and interleukin-3 (IL3) with either Flt3
      ligand (FLT3L) or stem cell factor (SCF). Using these two combinations, we
      obtained the same degree of day 14 CFU-GM expansion (3.1 +/- 0.5 and 3.4 +/- 0.7
      fold expansion). FISH analysis showed that 5FU pretreatment significantly
      favoured a higher frequency of Ph-negative cells after expansion in liquid
      culture. Moreover, after 5FU pretreatment, the mean (+/-SEM) percentage of Ph
      negativity was significantly greater for IL1alpha-IL3-FLT3L compared to IL1alpha
      IL3-SCF (19.1 +/- 2.5% v 14.8 +/- 2.3%, P=0.009, n = 7). The output long-term
      culture initiating cells (LTC-IC) which could only be detected after 5FU
      pretreatment and the combination, IL1alpha-IL3-FLT3L were all Ph negative by FISH
      analysis. Thus, a subset of Ph-negative cells was selected from CML PB by 5FU and
      expanded using the combination of cytokines IL1alpha-IL3-FLT3L and IL1alpha-IL3
      SCF. Ex vivo expansion of putatively normal haemopoietic progenitor cells is
      feasible in CML.

PMID- 9266953
TI  - Crossover study of the haematological effects and pharmacokinetics of
      glycosylated and non-glycosylated G-CSF in healthy volunteers.
AB  - A cross-over study of glycosylated and non-glycosylated G-CSF was performed in 20
      healthy male volunteers to compare the effects of the different forms of G-CSF,
      the extent of inter-individual progenitor cell mobilization and to determine
      whether any differences observed were related to the serum concentrations of G
      CSF attained. The peak WBC achieved during 6 d of G-CSF administration at a dose
      of 5 microg/kg/d was significantly higher with the glycosylated than the non
      glycosylated product (P = 0.02) as was the peak level of granulocyte-monocyte
      colony forming cells (GM-CFC) (P=0.03). The average GM-CFC count on days 5, 6 and
      7 was 28% higher with the glycosylated product (P=0.003). Serum concentrations of
      G-CSF achieved were significantly higher with the non-glycosylated G-CSF,
      however, suggesting that the difference in bio-efficacy was not due to a
      difference in G-CSF stability. Marked inter-individual variation in progenitor
      mobilization was observed, but this was not related to serum G-CSF levels. The G
      CSF concentrations on day 6 were approximately one third of those on day 1, with
      both forms of G-CSF.

PMID- 9266954
TI  - Detection of donor-derived Langerhans cells in MHC class II immunodeficient
      patients after allogeneic bone marrow transplantation.
AB  - T-cell dependent immune response is initiated by dendritic cells, which are the
      only leucocytes able to prime naive CD4-positive T cells. Langerhans cells (LC)
      are dendritic cells characterized by their localization within the epidermis,
      their dendritic shape, and their expression of specific markers such as major
      histocompatibility complex (MHC) class II molecules, CD1a and S100 protein. We
      retrospectively studied the phenotype of LC in the skin of eight children with
      MHC class II deficiency (bare lymphocyte syndrome) after allogeneic bone marrow
      transplantation (BMT). The presence of donor-derived MHC class II positive LC
      within the epidermis was studied by immunohistochemistry on skin biopsies
      performed for the determination of graft-versus-host disease. MHC class II
      positive LC were undetectable in the epidermis of a child who did not engraft and
      of three children 13-18 d after HLA-mismatched BMT, despite engraftment. However,
      donor-derived MHC class II positive LC were detected in four children 9-43 d
      after HLA-identical BMT. Our results demonstrate that LC can differentiate or
      expand very quickly, as early as within 9 d after BMT.

PMID- 9266955
TI  - Epstein-Barr virus associated B-cell lymphoma after autologous bone marrow
      transplantation for T-cell acute lymphoblastic leukaemia.
AB  - Epstein-Barr virus associated lymphoproliferative disease after autologous bone
      marrow transplantation (ABMT) has rarely been reported. We report a case of B
      cell lymphoma following ABMT for T-acute lymphoblastic leukaemia; bone marrow was
      purged in vitro with monoclonal antibodies to remove T cells. Immunoglobulin and
      T-cell receptor gene rearrangement studies were used to demonstrate clonality and
      to show that this patient developed a second neoplasm after ABMT. EBV proteins
      and genome (type A) were present in post-transplantation lymphoma, suggesting a
      causative role in its development.

PMID- 9266956
TI  - Detection of melanoma cells in peripheral blood stem cell harvests of patients
      with progressive metastatic malignant melanoma.
AB  - The detection of melanocyte-specific messenger RNA in patients with malignant
      melanoma suggests the potential contamination of peripheral blood stem cell
      (PBSC) harvests by neoplastic cells. In this study, the melanocyte-specific
      transcripts of tyrosinase and Melan-A/MART-1 were used to detect neoplastic cells
      in PBSC harvests of nine metastatic malignant melanoma patients. Only one
      patient's PBSC harvest tested positive for tyrosinase. All harvests were negative
      for Melan-A/MART-1. Our results suggest that contamination of PBSC harvests with
      neoplastic cells may not contribute to disease progression following high-dose
      chemotherapy in advanced malignant melanoma.

PMID- 9266957
TI  - Oral contraceptives and venous thromboembolism: acquired APC resistance?

PMID- 9266958
TI  - Increased numbers of bone marrow blasts in acute myeloid leukaemia patients
      treated with G-CSF after chemotherapy.

PMID- 9266959
TI  - Maternal IVIG in neonatal alloimmune thrombocytopenia.

PMID- 9266960
TI  - Hepatitis GBV-C and aplastic anaemia.

PMID- 9266961
TI  - Ultraviolet light-induced G2 phase cell cycle checkpoint blocks cdc25-dependent
      progression into mitosis.
AB  - In response to low doses of ultraviolet (U.V.) radiation, cells undergo a G2
      delay. In this study we have shown that the G2 delay results in the accumulation
      of inactive forms of cyclin B1/cdc2 and both the G2 and mitotic complexes of
      cyclin A/cdk. This appears to be through a block in the cdc25-dependent
      activation of these complexes. The expression and localisation of cyclin A and
      cyclin B1/cdk complexes are similar in U.V.-induced G2 delay and normal early G2
      phase cells. Cdc25B and cdc25C also accumulate to normal G2 levels in U.V.
      irradiated cells, but the mitotic phosphorylation associated with increased
      activity of both cdc25B and cdc25C is absent. The cdc25B accumulates in the
      nucleus of U.V. irradiated cells and in normal G2 phase cells. Thus the block in
      cyclin B/cdc2 activation is in part due to the physical separation of cyclin
      B/cdc2, localised in the cytoplasm, from the cdc25B and cdc25C phosphatases
      localised in the nucleus. The data positions the U.V.-induced G2 checkpoint at
      either the S/G2 transition or early G2 phase, prior to the activation of cyclin
      A/cdk2.

PMID- 9266963
TI  - Nitric oxide-mediated apoptosis of K-1735 melanoma cells is associated with
      downregulation of Bcl-2.
AB  - Recent studies have shown that the treatment of nonmetastatic K-1735 murine
      melanoma cells with cytokines induces the production of nitric oxide (NO) and
      hence cell death. The purpose of this study was to determine the mechanism of
      this cytokine-induced NO-mediated apoptosis. Incubation of nonmetastatic K-1735
      cells with interleukin-1 alpha (IL-1alpha) and interferon-gamma (IFN-gamma)
      induced high NO production, Bcl-2 downregulation, and apoptotic cell death. In
      contrast, incubation of metastatic K-1735 cells with IL-1alpha and IFN-gamma did
      not induce significant production of NO, downregulation of Bcl-2, or cell death.
      The exposure to exogenous NO derived from the NO donors, sodium nitroprusside
      (SNP), or GEA5024 produced a dose-dependent apoptotic cell death in both the
      metastatic and nonmetastatic K-1735 cells, which was associated with
      downregulation of Bcl-2 at the mRNA level and, to a lesser extent, at the protein
      level. Nonmetastatic and metastatic K-1735 cells transfected with the Bcl-2 gene
      were more resistant to apoptosis mediated by both endogenous and exogenous NO.
      Subsequent to intravenous injection, the tumor cells transfected with the Bcl-2
      gene had an increased survival rate in the lungs of nude mice and produced a
      higher number of experimental lung metastases. These data suggest that NO-induced
      apoptosis in K-1735 melanoma cells is associated with downregulation of Bcl-2.

PMID- 9266962
TI  - Transcriptional squelching by ectopic expression of E2F-1 and p53 is alleviated
      by proteasome inhibitors MG-132 and lactacystin.
AB  - The transcription factors p53 and E2F-1 play important roles in the control of
      cell cycle progression. In transient transfection experiments, expression of E2F
      1, other E2F family members, or p53 squelched transcription from cotransfected
      plasmids in a dose-dependent manner. Although the proteasome inhibitors MG-132
      and lactacystin markedly increased the level of expression of E2F-1 and p53,
      these inhibitors completely alleviated squelching by both proteins. Several
      observations indicate MG-132 alleviates squelching by influencing the
      conformation of newly synthesized p53 and E2F-1:MG-132 increased the fraction of
      wild type p53 bound by a monoclonal antibody which preferentially recognizes
      mutant conformers of p53, increased binding of hsp70 to p53 and inhibited nuclear
      accumulation of both p53 and E2F-1, but not the pocket protein p107. The protease
      inhibitors ALLN and ALLM did not influence expression of E2F-1 or p53, nor did
      they alleviate squelching by either transcription factor. Because MG-132 and
      lactacycstin are highly specific inhibitors of the proteasome protease, our
      results suggest that the proteasome influences post-translational processes
      involved in proper folding and cytoplasmic clearing of E2F-1 and p53.

PMID- 9266964
TI  - Mutations of thyrotropin receptor isolated from thyroid autonomous functioning
      adenomas confer TSH-independent growth to thyroid cells.
AB  - TSH receptor mutants in the VI transmembrane segment, found in thyroid
      autonomously functioning adeonomas, have been expressed in differentiated thyroid
      cells. All mutant receptors constitutively stimulated adenylyl cyclase. The
      biological activity, measured as cAMP production relative to the wild type
      receptor, was specific for each mutant in transient and stable transfection
      assays. Cells expressing these mutants proliferated in the absence of TSH. The
      rate of growth in the absence of TSH paralleled basal cAMP production for each
      mutant receptor. Low TSH concentrations stimulated the growth of mutant receptor
      expressing cells, and not of the cells expressing the wild type receptor. Also,
      the entry in the cell cycle and the plating efficiency were markedly stimulated
      by the expression of the mutant receptors. These data provide a molecular link
      between the occurrence of TSH receptor mutations and thyroid autonomously
      functioning adenomas.

PMID- 9266965
TI  - Intercellular induction of apoptosis in transformed cells does not depend on p53.
AB  - Transformed fibroblast from p53 null/null mice were tested for their sensitivity
      to intercellular induction of apoptosis by TGF-beta-treated nontransformed cells.
      They were found to be as sensitive as p53-positive transformed cells. Based on
      morphological criteria, detection of chromatin condensation and DNA strand
      breaks, death of p53-negative transformed cells was due to apoptosis. p53
      negative nontransformed cells were as efficient in the induction of apoptosis in
      transformed cells as p53-positive nontransformed cells. These data show that
      intercellular induction of apoptosis in transformed cells does not depend on
      functional p53. Therefore it may be assumed that mutations of p53 or modulation
      of its concentration are without relevance for this particular aspect of control
      of oncogenesis.

PMID- 9266966
TI  - BRK tyrosine kinase expression in a high proportion of human breast carcinomas.
AB  - BRK is a recently described non receptor protein tyrosine kinase whose mRNA was
      found to be expressed in human breast tumours and breast cancer cell lines.
      Expression of BRK in fibroblasts and mammary epithelial cells has been shown to
      enhance their ability to grow anchorage independently, and mammary epithelial
      cells expressing BRK acquire a potentiated mitogenic response to epidermal growth
      factor. In order to investigate further the expression of BRK in breast cancers,
      we have isolated monoclonal antibodies specifically recognising the protein.
      Whereas BRK expression was low or undetectable in normal mammary tissue and
      benign lesions, approximately two-thirds of breast tumours expressed appreciable
      levels, and 27% of tumours over expressed BRK by fivefold or more (up to 43x).
      This expression pattern was mirrored in a comparison of cell lines derived either
      from normal mammary epithelial cells or from carcinomas. BRK expression was found
      to be constant throughout the cell cycle, and did not vary with cell
      proliferation rate. A consideration of this expression data, in conjunction with
      BRK's demonstrated ability to deregulate the proliferation of mammary epithelial
      cells, supports the hypothesis that the over expression of BRK in a high
      proportion of breast carcinomas is a functionally important factor in their
      evolution.

PMID- 9266967
TI  - Two tandem and independent sub-activation domains in the amino terminus of p53
      require the adaptor complex for activity.
AB  - The ability of p53 to function as a tumor suppressor is linked to its function as
      a transcriptional activator, since p53 mutants that do not transactivate are
      unable to suppress tumor cell growth. Previous studies identified an activation
      domain in the amino terminal 40 residues of the protein, a region that binds to
      several general transcription factors and to some oncogene products. For example,
      mdm-2, a cellular oncoprotein, binds to this region and represses p53
      transactivation. Here we describe a new activation domain within the amino
      terminus of p53 that maps between amino acids 40-83, and whose residues trp-53
      and phe-54 are critical for function both in yeast and in mammalian cells. In
      vivo studies in yeast show that the new activation subdomain, unlike the
      previously described, is mdm-2 independent. Both p53 activation subdomains (1-40
      and 40-83) require the yeast adaptor complex ADA2/ADA3/GCN5 for transcriptional
      activation. Moreover, since activation by p53 requires GCN5's enzymatic histone
      acetyltransferase domain, p53 may regulate gene expression by influencing
      chromatin modification.

PMID- 9266968
TI  - Ligand-independent activation of fibroblast growth factor receptor-2 by carboxyl
      terminal alterations.
AB  - To assess the effect(s) of the C-terminal domain on FGFR2 function, we engineered
      a series of mutant FGFR2 cDNAs encoding deletions in the C-terminus of the
      receptor and compared their growth properties in NIH3T3 fibroblasts. In contrast
      to FGFR2-WT, receptors with C-terminal truncations induced ligand-independent
      transformation of NIH3T3 cells and transfectants expressing these mutant
      receptors efficiently formed colonies in semisolid medium. Introduction of point
      mutations (Y to F) into the C-terminus of FGFR2 at positions 813, 784 or 780
      revealed that these mutant receptors also displayed activities similar to that of
      C-terminally truncated receptors. C-terminally altered FGF receptors did not show
      an increase in the basal level of receptor phosphorylation compared to that of
      FGFR2-WT suggesting that elevated receptor phosphorylation does not underlie the
      transforming activity of these receptors. Interestingly, expression of
      transforming FGFR2 derivatives, unlike H-Ras transformed cells, did not result in
      the activation of the mitogen-activated protein kinases (MAPKs), p42/ERK2 and
      p44/ERK1, indicating that this pathway is not constitutively active in FGFR2
      transformed cells. Finally, we report the overexpression of FGFR2 mRNA and
      protein in several human tumor cell lines suggesting activation of the receptor
      in these tumors.

PMID- 9266969
TI  - The transcriptional repressor ICER and cAMP-induced programmed cell death.
AB  - The cAMP pathway plays a central role in the response to hormonal signals for
      cell proliferation, differentiation and apoptosis. In IPC-81 leukaemia cells,
      activation of the cAMP pathway by prostaglandin E1 treatment, or other cAMP
      elevating agents, induces apoptosis within 4-6 h. Inhibition of mRNA or protein
      synthesis during the first 2 h of cAMP induction protects cells from apoptosis,
      suggesting a requirement for early gene expression. cAMP-dependent protein kinase
      phosphorylates a class of nuclear factors and thereby regulates the transcription
      of a specific set of genes. Here we show that CREM (cAMP Responsive Element
      Modulator) expression is induced rapidly upon prostaglandin E1 treatment of IPC
      81 cells. The induced transcripts correspond to the early product ICER (Inducible
      cAMP Early Repressor). ICER expression remains elevated until the burst of cell
      death. Protein synthesis inhibitors which prevent cAMP-induced apoptosis also
      block de novo ICER synthesis. Transfected IPC-81 cell lines, constitutively
      expressing high level of ICER are resistant to cAMP-induced cell death. In these
      transfected cells, cAMP fails to upregulate the ICER transcripts demonstrating
      that ICER exerts strongly its repressor function on CRE-containing genes. That an
      early expression of ICER blocks apoptosis, suggests that gene repression by
      endogenous ICER in IPC-81 is insufficient or occurs too late to protect cells
      against death. ICER transfected cells rescued from cAMP-induced apoptosis are
      growth arrested. It shows for the first time that CREM activation directly
      participates to the decision of the cell to die. ICER, by sequentially repressing
      distinct sets of CRE-containing genes could modulate cell fate.

PMID- 9266970
TI  - Dexamethasone induces apoptosis of multiple myeloma cells in a JNK/SAP kinase
      independent mechanism.
AB  - The stress-activated protein kinases (SAPKs), also known as c-Jun amino-terminal
      kinases (JNKs), are activated in response to diverse stimuli including DNA
      damage, heat shock, interleukin-1, tumor necrosis factor-alpha and Fas. Although
      all these inducers cause apoptosis, whether SAPK/JNK activation is required for
      apoptosis is controversial. In this study, we demonstrate that ionizing radiation
      (IR) and dexamethasone (Dex) induce apoptosis in multiple myeloma (MM) derived
      cell lines, as well as in patient cells. IR-induced apoptosis is associated with
      activation of SAPK/JNK and p38 kinase, in contrast to Dex-induced apoptosis,
      which is not associated with activation of stress kinases. Moreover, Dex-induced
      apoptosis is associated with a significant decrease in the activities of mitogen
      activated protein kinase (MAPK) and p70S6K, whereas IR-treatment does not alter
      the activity of these kinases. Both IR and Dex induce poly (ADP ribose)
      polymerase (PARP) cleavage, a signature event of apoptosis. Finally, interleukin
      6 (IL-6) inhibits Dex-induced apoptosis, downregulation of MAP and p70S6K growth
      kinases and PARP cleavage; in contrast, IL-6 does not inhibit IR-induced
      apoptosis, activation of SAPK/JNK, and PARP cleavage. Taken together, our
      findings suggest that SAPK/JNK activation is not required for apoptosis in MM
      cells, and that there are at least two distinct apoptotic signaling pathways: (i)
      SAPK/JNK-associated, which is induced by IR and unaffected by IL-6; and (ii)
      SAPK/JNK-independent, which is induced by Dex, associated with downregulation of
      MAPK and p70S6K and inhibited by IL-6.

PMID- 9266971
TI  - Biochemical characterization of C3G: an exchange factor that discriminates
      between Rap1 and Rap2 and is not inhibited by Rap1A(S17N).
AB  - A catalytically active fragment of the Rap-specific guanine-nucleotide exchange
      factor C3G was expressed in E coli. It was purified and its interaction with GTP
      binding proteins was investigated using fluorescence spectroscopy. C3G stimulates
      GDP dissociation from Rap1, but not from Rap2, neither from Bud1, which is
      believed to be the yeast homologue of Rap1 nor from all other proteins of the
      human Ras-subfamily. Like the corresponding fragment from CDC25Mm, the increase
      in the GDP dissociation rate is linear with increasing concentration of Rap1A x
      GDP up to 100 microM, indicating an apparent K(M) higher than 100 microM. Unlike
      the Ras-CDC25Mm system, the Rap1A(S17N) mutant does not inhibit the C3G-activated
      guanine nucleotide dissociation from wild-type Rap1A in vitro. These data suggest
      that Rap1A(S17N) is unlikely to titrate away C3G in vivo, the proposed mechanism
      by which S17N-mutants exert their dominant negative effects.

PMID- 9266972
TI  - A variant form of ETS1 induces apoptosis in human colon cancer cells.
AB  - We have previously shown that the human ETS1 protein (p51-ETS1), when ectopically
      expressed in colon cancer cell lines, is able to reduce its tumorigenicity
      without affecting its growth properties. To understand the mechanism of tumor
      reduction, we have expressed two different forms of ETS1 in colon cancer cell
      lines. Data presented in this paper indicate that the naturally occurring spliced
      variant protein, p42-ETS1, lacking the region encoded by ETS1 exon VII, represses
      the tumorigenicity, while p51-ETS1 reduces the tumorigenicity. Repression of
      tumorigenicity mediated by p42-ETS1 appears to be caused by its ability to induce
      apoptosis in epithelial cancer cells. This work can have profound medical
      significance in that it may open up new insights into the potential role of the
      p42-ETS1 in the induction of apoptosis in epithelial cell cancers and may provide
      a rationale for its use for potential gene therapy experiments to initiate cell
      death in cancer cells.

PMID- 9266973
TI  - DNA-conformation is an important determinant of sequence-specific DNA binding by
      tumor suppressor p53.
AB  - Sequence-specific transactivation of target genes is one of the most important
      molecular properties of the tumor suppressor p53. Binding of p53 to its target
      DNAs is tightly regulated, with modifications in the carboxy-terminal regulatory
      domain of the p53 protein playing an important role. In this study we examined
      the possible influence of DNA structure on sequence-specific DNA binding by p53,
      by analysing its binding to p53 consensus elements adopting different
      conformations. We found that p53 has the ability to bind to consensus elements
      which are present in a double-helical form, as well as to consensus elements
      which are located within alternative non-B-DNA structures. The ability of a
      consensus element to adopt either one of these conformations is dependent on its
      sequence symmetry, and is strongly influenced by its sequence environment. Our
      data suggest a model according to which the conformational status of the target
      DNA is an important determinant for sequence-specific DNA binding by p53.
      Modifications in the carboxy-terminal regulatory region of p53 possibly determine
      the preference of p53 for a given DNA conformation.

PMID- 9266974
TI  - Loss of heterozygosity of a locus on 17p13.3, independent of p53, is associated
      with higher grades of astrocytic tumours.
AB  - Amongst the human astrocytic tumours, the commonest of primary brain tumours, the
      clinical outcome of astrocytoma (AS) is significantly better than anaplastic
      astrocytoma (AA) and glioblastoma multiforme (GBM). Often, low grade tumours can
      progress to or recur with a more malignant phenotype. Recent loss of
      heterozygosity (LOH) reports suspect the involvement of a tumour suppressor gene,
      different from p53, in the 17p13.3 region of the human chromosome. However, the
      effect of LOH of 17p13.3 region on tumour histology at presentation and prognosis
      is as yet undefined. As a first step to define the role of this putative oncogene
      in astrocytic tumour progression, we correlated the LOH of a locus, D17S379, in
      17p13.3 region and the p53 locus in 17p13.1 region with the histopathology of
      astrocytic tumours by PCR based microsatellite and restriction fragment length
      polymorphism of DNA extracted from microdissected paraffin sections of 45
      astrocytic tumours of different histopathological grades. LOH of D17S379 was
      significantly associated (P=0.02) with AA and GBM (high grade malignancy), while
      no such preferential association was found with LOH of p53. There were no
      mutations in the exons 5 to 9 of p53 gene in the five tumours with LOH of D17S379
      but not of p53 region. In a case of AA with a heterogenous microscopic
      appearance, heterozygosity of D17S379 was lost only in the area with a more
      malignant histology while both areas had no LOH or mutation of p53. A locus at
      the 17p13.3 region, independent of the p53 locus, is involved in a large subset
      of astrocytic tumours during transformation into a more malignant phenotype, and
      thus may be a link in the chain of genetic events occurring in astrocytic tumour
      progression.

PMID- 9266975
TI  - Random selection: a model for poliovirus infection of the central nervous system.
AB  - Mixed infections occur in the natural environment, and also result from the use
      of mixed live vaccines. Some recipients of the trivalent oral poliovirus vaccine
      develop vaccine-associated paralytic poliomyelitis (VAPP). Numerous serotypes and
      recombinant genotypes of vaccine-derived polioviruses may be found in stool
      samples from such cases. To investigate the relationship between the
      multiplication of various genotypes at the primary replication site in the gut
      and the infection outcome in the central nervous system (CNS), the viruses
      excreted on consecutive days by two patients with VAPP were compared with the
      viruses isolated from the CNS. The genotypes from stools were numerous and varied
      with time in both cases, suggesting a multiplication of the viruses in multiple
      foci in the gut. Where the CNS isolated virus clearly corresponded to one of the
      many viruses detected in stool, this virus was unexpectedly less neurovirulent
      than others isolated from stool. To assess the mechanism by which viruses with
      different degrees of neurovirulence are selected in the CNS, transgenic mice
      sensitive to poliovirus infection were inoculated extraneurally with mixtures of
      two phenotypically different viruses at different neuropathogenic doses. The
      virus(es) inducing neurological disease was then isolated from the CNS. At less
      than 100% input neuropathogenic dose of both inoculated viruses, individual mice
      were affected stochastically by the virus variants from the mixture. Extrapolated
      to humans, this selection pattern might explain the occurrence of CNS infections
      with less neurotropic viruses derived from an extraneural pool containing also
      highly neurotropic viruses.

PMID- 9266976
TI  - Immunogenic, non-infectious polio subviral particles synthesized in Saccharomyces
      cerevisiae.
AB  - Polioviral genes coding for P1, the precursor for the structural proteins, and
      3CD, the viral protease, were cloned in a Saccharomyces cerevisiae inducible
      expression system. N-antigenic empty capsids could be isolated from the yeast
      cell extract provided that pirodavir, a capsid-binding compound and capsid
      stabilizer, was added during the induction period and during purification.
      Purification was by immunoaffinity chromatography. The purified empty capsids had
      the same immunogenicity as poliovirus virions. The techniques described might be
      useful for the production of new non-infectious vaccines.

PMID- 9266977
TI  - Chimeric coxsackie B3 virus genomes that express hybrid coxsackievirus-poliovirus
      2B proteins: functional dissection of structural domains involved in RNA
      replication.
AB  - The 2B proteins of coxsackievirus and poliovirus (PV) share significant
      structural similarity and exhibit similar biochemical activities, namely
      inhibition of protein secretion and modification of membrane permeability. Both
      proteins contain two hydrophobic domains in the carboxy-terminal two-thirds of
      their sequence, of which one has the potential to form a cationic amphipathic
      alpha-helix. To gain more insight into the structural requirements of enterovirus
      protein 2B for its functioning in viral RNA replication, a chimeric cDNA approach
      was used. Chimeric coxsackie B3 virus (CBV3) genomes were constructed that
      expressed either the entire PV 2B protein or hybrid proteins in which specific
      segments of CBV3 2B were substituted by their corresponding PV counterparts. In
      vitro synthesis and processing of the chimeric polyproteins showed no
      abnormalities. CBV3 genomes carrying the entire PV 2B gene failed to replicate. A
      chimeric genome that expressed a hybrid 2B protein consisting of the amino
      terminal one-third of PV and the remainder of CBV3 yielded viable viruses. In
      contrast, a 2B protein consisting of the amino-terminal one-third of CBV3 and the
      remainder of PV failed to drive replication. These data imply that a sequence
      specific interaction with another viral protein is required to drive RNA
      replication and suggest that the proposed sites of contact reside in the carboxy
      terminal two-thirds of 2B. Hybrid genomes in which either the amphipathic alpha
      helix or the other hydrophobic domain was replaced failed to replicate. The
      potential contribution of these domains to the structure and functioning of
      protein 2B are discussed.

PMID- 9266978
TI  - Influence of the 5' noncoding region of hepatitis A virus strain GBM on its
      growth in different cell lines.
AB  - Previous sequence analysis of consecutive passages of the hepatitis A virus (HAV)
      strain GBM/WT in human embryonic kidney cells (HEK cells), human embryonic lung
      fibroblasts (HFS cells) and in FRhK-4 cells (foetal rhesus monkey kidney cells)
      pointed to a host cell dependent cell culture adaptation of GBM/WT in HFS cells
      involving mutations in the 5' noncoding region (5'NCR). Multiple nucleotide
      changes occurred in the 5'NCR of the GBM genome after the cell line used for
      virus passage was changed from HEK cells to HFS cells. In contrast, no mutations
      in the 5'NCR occurred during the first 20 passages of GBM/WT in FRhK-4 cells. In
      order to analyse the influence of the 5'NCR on host cell specific adaptation of
      HAV strain GBM in different cell cultures, GBM/HM175 chimeras were constructed
      which contained 5'NCRs from different GBM variants by replacing the 5'NCR of the
      infectious clone pHAV/7. Parallel transfection assays in FRhK-4 and HFS cells,
      performed with transcripts from the chimeric GBM/HM175 constructs, showed that
      the 5'NCR of the GBM variant GBM/HFS is essential for virus growth in HFS cells.
      The GBM/HM175 chimeric RNA, which contained the 5'NCR of GBM/HFS, exclusively,
      was able to produce infectious virus after transfection of HFS cells. The growth
      of the different GBM/HM175 chimeras in FRhK-4 cells, in contrast, did not seem to
      be strongly influenced by a specific sequence of the 5'NCR.

PMID- 9266979
TI  - GB virus C E2 glycoprotein: expression in CHO cells, purification and
      characterization.
AB  - A 315 amino acid recombinant segment of the GB virus C (GBV-C) E2 envelope
      glycoprotein (E2-315) was expressed and secreted from CHO cells. E2-315 was
      purified by affinity chromatography using a monoclonal antibody directed to a
      FLAG sequence genetically engineered onto the C terminus of the recombinant
      protein. The secreted protein had a molecular mass of 48-56 kDa and was shown to
      be N-glycosylated. Amino acid sequencing confirmed the expected N-terminal
      sequence. Purified E2-315 was used to develop an ELISA for detection of E2
      antibodies in human sera. Antibodies to GBV-C E2 appeared to be directed toward
      conformational epitopes since human sera reactivity was detected in ELISA using
      native E2-315, but it was extremely weak or non-existent with denatured E2
      protein. The use of an ELISA which can detect human GBV-C E2 antibodies will be
      important in further understanding of the clinical significance and epidemiology
      of GBV-C.

PMID- 9266980
TI  - Expression of the dengue virus structural proteins in Pichia pastoris leads to
      the generation of virus-like particles.
AB  - We have expressed cDNA encoding the dengue virus structural proteins in Pichia
      pastoris by chromosomal integration of an expression cassette containing the
      dengue virus structural genes (CprME). The yeast recombinant E protein migrated
      during SDS-PAGE as a 65 kDa protein when analysed by Western blotting and
      radioimmunoprecipitation, which is the expected molecular mass for correctly
      processed and glycosylated E protein. Treatment with endoglycosidases showed that
      the recombinant E protein was modified by the addition of short mannose chains.
      The E protein migrated with a buoyant density of 1.13 g/cm3 when analysed using
      sucrose density gradient centrifugation. Spherical structures with an average
      diameter of 30 nm, whose morphology resembles dengue virions, were observed in
      the purified fractions using transmission electron microscopy. Furthermore, the
      virus-like particles were immunogenic in animals and were able to induce
      neutralizing antibodies. This is the first report that expression of the
      structural genes of a flavivirus in yeast is able to generate particulate
      structures that resemble virions.

PMID- 9266981
TI  - Monoclonal antibodies to the ORF5 product of porcine reproductive and respiratory
      syndrome virus define linear neutralizing determinants.
AB  - Complementary DNA encoding the ORF5 gene of a Quebec reference isolate (IAF-Klop)
      of porcine reproductive and respiratory syndrome virus (PRRSV) was cloned into
      the prokaryotic expression vectors pGEX-4T and pET21a to produce ORF5-glutathione
      S-transferase and ORF5-polyhistidine fusion proteins. Five hybridoma cell lines
      producing monoclonal antibodies (MAbs) to the 25 kDa viral envelope glycoprotein
      (GP5) were obtained from BALB/c mice immunized with the affinity chromatography
      purified GST-ORF5 fusion protein. The polypeptide specificity of these anti-PRRSV
      MAbs, belonging to the IgG1 isotype, was confirmed by Western immunoblotting
      assays with recombinant and native viral proteins, and by
      radioimmunoprecipitation using [35S]methionine-labelled concentrated
      extracellular virus. All these MAbs showed virus-neutralizing (VN) activity, with
      VN titres ranging from 1:32 to 1:128. Two MAbs (IAF-1B8 and IAF-8A8) reacted with
      similar titres with the modified live attenuated vaccine strain ATCC VR-2332, but
      all five failed to react to the prototype European strain, the Lelystad virus, in
      VN and indirect immunofluorescence tests. The results obtained suggest that these
      five anti-PRRSV MAbs are directed to serotype-specific linear neutralizing
      epitopes which are not affected by the absence of carbohydrate residues.

PMID- 9266982
TI  - Rinderpest virus isolates of different virulence vary in their capacity to infect
      bovine monocytes and macrophages.
AB  - Three isolates of rinderpest virus (RPV) with different in vivo virulence were
      able to infect and productively replicate in bovine monocytic cells. They
      differed in their kinetics of replication and the morphological changes induced
      in infected cultures. The highly virulent RPV-Saudi infected > 80% of cells
      within 6 days p.i. (m.o.i. = 0.1 TCID50 per cell). Under identical conditions, >
      50% of cells were infected by the 'mild' (causes minimal mortality in vivo)
      isolate RPV-Egypt, whereas only 25% were infected by the avirulent RPV-RBOK.
      Infection by all three viruses produced infectious progeny, induced the formation
      of syncytia and stellate cells with long processes, and down-regulated MHC class
      II expression; there was no apparent effect on MHC class I nor LFA-1. RPV-Saudi
      was the most efficient at generating progeny virus and producing syncytia. While
      RPV-RBOK was the least efficient at inducing syncytia, RPV-Egypt was the least
      efficient for progeny virus production. In contrast, RPV-Egypt was particularly
      efficient at inducing stellate cell formation and down-regulating MHC class II
      expression. These results indicate a relationship between in vivo virulence and
      the characteristics of replication and induced morphological changes in
      monocytes/macrophages. The down-regulation of MHC class II expression would offer
      a means by which the virus could evade immune recognition. This would be
      particularly useful for the more cell-associated, but less efficient at maturing,
      RPV-Egypt.

PMID- 9266983
TI  - Analysis of bovine respiratory syncytial virus envelope glycoproteins in cell
      fusion.
AB  - To compare the requirements for respiratory syncytial virus (RSV)-mediated cell
      fusion, the fusion (F), attachment (G) and small hydrophobic (SH) glycoproteins
      of bovine RSV (BRSV), ovine RSV (ORSV) and human RSV (HRSV) were expressed
      individually or coexpressed in either homologous or heterologous combinations in
      HeLa cells, using the vaccinia virus-T7 polymerase transient expression system.
      Cell fusion was examined by a reporter gene activation assay. Although the
      expression of the F protein alone or coexpression of the F and G proteins or the
      F and SH proteins induced cell fusion, coexpression of F, G and SH proteins
      induced extensive cell fusion. Coexpression of various combinations of envelope
      glycoproteins of BRSV, ORSV and HRSV indicated that substitution of heterologous
      SH protein affects the effective fusigenic properties of the BRSV F protein far
      more than that obtained by substituting the heterologous G protein.

PMID- 9266984
TI  - Multiplication and haemadsorbing activity of infectious salmon anaemia virus in
      the established Atlantic salmon cell line.
AB  - Infectious salmon anaemia virus (ISAV), which previously had never been isolated
      in any of the commercially available established fish cell lines, was
      successfully propagated in the continuous cell line Atlantic salmon (AS). The
      yield of infectious ISAV increased with the incubation time of virus-inoculated
      cells, demonstrated by in vivo infectivity trials in groups of Atlantic salmon.
      Trypsin treatment of the virus was not necessary for primary infection of AS
      cells with salmon-grown ISAV. The infection was non-cytopathic, but it was
      possible to detect virus-infected cells by a haemadsorption centre assay using
      Atlantic salmon erythrocytes. Pleomorphic enveloped virus particles were seen by
      transmission electron microscopy of infected AS cells. Elongated forms were
      observed, but spherical particles with diameters of 90-130 nm were commonest.
      Growth of ISAV was inhibited by actinomycin D but not by 5-bromo-2-deoxyuridine
      treatment, which indicates that ISAV may be an aquatic orthomyxovirus.

PMID- 9266985
TI  - Kinetics of viral RNA synthesis following cell-to-cell transmission of human
      immunodeficiency virus type 1.
AB  - The temporal appearance and levels of human immunodeficiency virus type 1 (HIV-1)
      tat, rev, nef, env and gag mRNA species were examined using a synchronized, one
      step, cell-to-cell HIV-1 infection model involving HUT-78 cells and HIV- 1
      persistently infected H3B cells. Individual mRNAs were quantified by RT-PCR using
      RNA standards transcribed in vitro from cDNA clones. Consistent with an infection
      that produces high yields of virus, significant levels of env and gag mRNAs were
      detected in the cytoplasm of infected cells late in the infection cycle. However,
      at no time after infection did levels of tat, rev and nef mRNA, which encode the
      regulatory proteins of HIV-1, exceed their levels present in the persistently
      infected virus donor H3B cells. The absence of early phase induction of these
      mRNAs is in contrast to what is observed in cell-free HIV-1 infections or in PMA
      stimulated HIV-1 chronically infected cell lines. Our results suggest that tat
      and rev mRNAs are already present in the cytoplasm of the persistently infected
      virus donor cells at levels sufficient for initiation and establishment of a
      highly productive infection in HIV-1 fusion-mediated infected cells. Thus, lack
      of sufficient Tat and Rev proteins is not likely to be the limiting factor for
      virus production in H3B cells, nor is increased production of these proteins
      likely to be the cause of the increased virus production seen following cell-to
      cell transmission.

PMID- 9266986
TI  - Human immunodeficiency virus type 1 incorporates both glycosyl
      phosphatidylinositol-anchored CD55 and CD59 and integral membrane CD46 at levels
      that protect from complement-mediated destruction.
AB  - Human immunodeficiency virus type 1 (HIV-1) can be either resistant or sensitive
      to complement-mediated destruction depending on the host cells. Incorporation of
      different levels of host cell CD46, CD55 and CD59 may account for this
      differential sensitivity to complement. However, it has not been determined
      whether CD46, CD55 and CD59 can all be incorporated at levels which protect
      virions. To determine whether each of these proteins can protect HIV-1, virions
      were derived from CHO cells expressing either human CD46, CD55 or CD59. Virions
      were shown to incorporate both glycosyl phosphatidylinositol (GPI)-anchored CD55
      and CD59 as well as transmembrane CD46. Importantly, all three virus preparations
      were significantly more resistant to complement lysis than control virus. This
      study demonstrates that HIV-1 incorporates both transmembrane and GPI-anchored
      complement control proteins from host cells and that both types of protein
      increase complement resistance of virus.

PMID- 9266987
TI  - Human immunodeficiency virus type 1 Rev- and Tat-specific cytotoxic T lymphocyte
      frequencies inversely correlate with rapid progression to AIDS.
AB  - Immunological correlates of AIDS-free survival after human immunodeficiency virus
      type 1 (HIV-1) infection are largely unknown. Cytotoxic T lymphocyte (CTL)
      responses are generally believed to be a major component of protective immunity
      against viral infections. However, the relationship between HIV-1-specific CTL
      responses and disease progression rate is presently unclear. Here we show in
      twelve HIV-1-infected individuals that detection of Rev-specific CTL precursors
      (CTLp) early in the asymptomatic stage, as well as detection of Rev- and Tat
      specific CTLp later during follow-up, inversely correlate with rapid disease
      progression. No such correlation was found for detection of CTLp against Gag, RT
      or Nef. Further studies are required to determine whether a protective mechanism
      is indeed the basis of the observed correlation. The data presented are in
      agreement with the hypothesis that CTL against proteins that are important for
      early viral transcription and translation are of particular importance in
      protection from rapid disease progression.

PMID- 9266988
TI  - Mechanisms of protection induced by attenuated simian immunodeficiency virus. I.
      Protection cannot be transferred with immune serum.
AB  - To evaluate its role in protection, immune serum was collected from four macaques
      which were chronically infected with live attenuated simian immunodeficiency
      virus (SIVmacC8) and had resisted challenge with wild-type SIVmacJ5. The immune
      serum was transferred to two naive cynomolgus macaques by intraperitoneal
      injection (11 ml/kg). Four control macaques received an intraperitoneal injection
      of normal saline. One day later, all macaques were challenged with 10 MID50 of
      the J5M challenge stock of SIV. After challenge, all macaques became infected as
      determined by virus co-culture and diagnostic PCR. Virus loads in PBMC at 2 weeks
      post-challenge were indistinguishable between the two groups of macaques. Thus,
      the failure of passive immunization to transfer protection indicates that serum
      components alone are not sufficient to mediate the potent protection obtained
      using live attenuated vaccines. This is the first time that serum has been
      transferred from animals known to be protected against superinfection.

PMID- 9266989
TI  - Macaques infected with attenuated simian immunodeficiency virus resist
      superinfection with virulence-revertant virus.
AB  - Macaques infected with attenuated simian immunodeficiency virus (SIVmac) can
      resist superinfection challenge with virulent virus, showing the potential of
      live attenuated virus as an AIDS vaccine. Superinfection resistance does not,
      however, prevent the generation of virulent virus in vivo, suggesting that such
      virus may circumvent the resistance effect. Here, we show that three macaques
      already infected with the attenuated molecular clone SIVmacC8 were resistant to
      superinfection with virulent virus that arose in vivo following repair of a 12 bp
      attenuating lesion in the nef/3' LTR. In contrast, four naive animals became
      infected following inoculation with blood taken from the macaque in which
      virulent virus arose. Loss of nef-specific cytotoxic T lymphocyte (CTL) responses
      followed repair of the attenuating lesion within nef in the donor animal,
      suggesting the possibility of escape from CTL-driven selection pressure.

PMID- 9266990
TI  - Mouse model to study the replication of primate foamy viruses.
AB  - A mouse model was developed to study the virus-host interaction of molecularly
      cloned human foamy virus (HFV) in vivo. The infectious process was analysed in
      two mouse strains, CBA/Ca and C57BL/6J, over a period of 24 weeks by PCR on DNAs
      from various animal tissues; virus serology was examined by immunoblotting. The
      infection persisted in both mouse strains and did not induce clinical symptoms.
      Upon infection of adult CBA/Ca mice HFV became detectable by PCR in an increasing
      number of organs over time. In contrast, in C57BL/6J mice, after an initial phase
      of dissemination, viral DNA sequences were found only in a few organs.
      Interestingly, the different course of infection was accompanied by differences
      in the antiviral immune response. In particular, C57BL/6J mice were high
      responders with respect to antibodies to the viral Bet protein, while CBA/Ca mice
      were low responders.

PMID- 9266991
TI  - Immunization with a mouse mammary tumour virus envelope protein epitope protects
      against tumour formation without inhibition of the virus infection.
AB  - BALB/c mice were immunized with the EP3 surface epitope of the mouse mammary
      tumour virus (MMTV) gp52 envelope protein before systemic infection with
      MMTV(C3H) or MMTV(SW). Analysis of the successive stages of the virus infection
      showed that although these mice were protected against mammary tumour formation,
      earlier stages of the infection were not inhibited, as reflected by the
      persisting superantigen-induced activation and deletion of Vbeta-specific T
      cells. Transplacental transfer of maternal anti-EP3 immunoglobulins to newborns
      did not protect them from infection through the Peyer's patches. Preincubation of
      the MMTVs with an anti-EP3 serum before injection, however, successfully
      inhibited the early stages of the infection. Results from this study show that to
      inhibit infection by MMTV efficiently, the virus must be neutralized before its
      interaction with the cell membrane, and that the affinity of the virus-membrane
      interaction is higher than that of the virus-antibody interaction.

PMID- 9266993
TI  - Deletion mapping of functional domains in the rotavirus capsid protein VP6.
AB  - VP6, the major capsid protein of rotavirus, oligomerizes into trimers that
      constitute the intermediate shell of the virions. In order to map functional
      domains in this protein, we introduced seven internal in-frame deletions within
      the coding region of gene 6 of human rotavirus strain Wa. Regions of homology
      among the VP6 proteins of group A and group C rotaviruses were targeted for
      deletion mutagenesis. The mutant VP6 proteins were expressed in mammalian cells
      using the recombinant vaccinia virus system and were examined for their ability
      to oligomerize into trimers as well as to assemble into double-layered virus-like
      particles upon coexpression with the rotavirus core protein VP2. Deletions that
      abolished trimerization defined a domain (residues 246 to 314) that maps within a
      larger region previously found to be critical for oligomerization (amino acids
      105 to 328). When the capacity of each mutant to assemble into double-layered
      virus-like particles was analysed, three different assembly phenotypes were
      observed. Phenotype I was represented by two deletion mutants lacking residues
      246 to 250 and 308 to 314 that produced particles with efficiencies similar to
      that of wild-type VP6. Phenotype II, characterized by a moderate decrease in the
      efficiency of particle assembly with respect to that of wild-type VP6, included
      two mutants with deletions at the C terminus of the protein. Phenotype III was
      exhibited by three mutants whose abilities to assemble into double-layered virus
      like particles were drastically impaired. Two of these mutants define a
      previously unidentified assembly domain (amino acids 122 to 147) at the N
      terminus of rotavirus VP6.

PMID- 9266992
TI  - Use of the bovine leukaemia virus LTR U3 promoter for expressing antisense
      antiviral RNAs and competitive inhibition of viral infection in cell culture.
AB  - Use of viral inducible promoters which can be activated by virus-specific
      transactivator proteins to drive expression of antisense (as)RNA genes appears to
      be an attractive approach to inhibit virus infections in vivo. To this end, we
      have constructed an asRNA gene expressed from the bovine leukaemia virus (BLV) U3
      promoter that is complementary to the R-U5 region of the BLV genome. This is the
      region that is most susceptible to inhibition by asRNA. With plasmid pLU, which
      expresses the asRNA gene under the control of the BLV U3 promoter, 75% inhibition
      of virus replication was attained in CC81 cells (the molar ratio of pLU DNA over
      BLV proviral DNA in the transfection mixture was 5:1). Plasmid pLT, which
      contains only the BLV U3 promoter without any asRNA-coding region, also
      efficiently (up to 60%) inhibited virus replication when cotransfected with BLV
      proviral DNA at a ratio of 20:1. It was suggested that competition between
      functional and 'empty' viral promoters for the viral transactivator protein
      p38tax could account for this inhibition. An immunoblotting assay showed that in
      the presence of nuclear extracts from CC81 cells exogenous BLV p38tax
      specifically associates with its responsive sequence located in the BLV U3
      promoter. Moreover, the additional expression of p38tax in CC81 cells abolishes
      the inhibitory effect of the empty viral promoter. These observations suggest a
      new mechanism of BLV inhibition caused, most probably, by sequestering of the
      viral transactivator protein.

PMID- 9266994
TI  - Human genital tissues containing DNA of adeno-associated virus lack DNA sequences
      of the helper viruses adenovirus, herpes simplex virus or cytomegalovirus but
      frequently contain human papillomavirus DNA.
AB  - The detection of DNA of the helper virus-dependent adeno-associated virus type 2
      (AAV-2) in biopsies of material from spontaneous abortion and in tissue samples
      from the uterus raises the question of whether sequences of known helper viruses
      can be detected simultaneously within the same specimen despite the lack of
      histological evidence for the presence of lytic viruses. Therefore, we performed
      PCR analyses with primers detecting DNA sequences of viruses (adenovirus, herpes
      simplex virus and human cytomegalovirus) known for their helper activity in the
      replication of adeno-associated viruses. In addition, PCR was performed to detect
      DNA of human papillomaviruses (HPV), which were recently shown to be able to help
      AAV replication in vitro. In no cases were sequences of the known helper viruses
      found. However, HPV DNA was detected in approximately 60% of paraffin sections
      from uterus biopsies and cervical lesions containing AAV DNA and in approximately
      70% of material from early miscarriage. This finding suggests that HPV may be a
      helper virus for AAV.

PMID- 9266995
TI  - Regulation of human papillomavirus type 16 DNA replication by E2, glucocorticoid
      hormone and epidermal growth factor.
AB  - The E1 and E2 proteins are the only human papillomavirus (HPV) proteins required
      for transient replication of plasmids containing the viral origin. The E2 gene
      products play key roles in both viral transcription and replication. In this
      study we have analysed in further detail the nature of the association between E1
      and E2 using a series of E2 proteins mutated in conserved regions of the N
      terminal domain. These proteins were tested for their ability to activate
      transcription and to stimulate viral DNA replication. Several of these mutants
      revealed that the two functions of E2 can be separated, and that they define
      three widely spaced regions of the N-terminal domain which are important for DNA
      replication, two of which retain E1-binding activity. This suggests that E2 may
      have a role in viral DNA replication other than simply localizing E1 to the
      origin of replication. Additional important elements for regulating viral gene
      expression have been shown to be glucocorticoid hormones and epidermal growth
      factor (EGF). We show here that they may also be involved in regulating viral DNA
      replication. Our studies show that the addition of glucocorticoid hormone
      significantly stimulates viral DNA replication. In contrast, addition of EGF
      results in modest repression of viral DNA replication. These results have
      important implications for the pathogenesis of HPV infection and suggest that the
      relative levels of E2, glucocorticoid hormone and EGF may significantly affect
      the outcome of an HPV infection.

PMID- 9266996
TI  - Apoptosis of cord blood T lymphocytes by herpes simplex virus type 1.
AB  - We investigated apoptosis induced by herpes simplex virus type 1 (HSV-1) in cord
      blood T lymphocytes by using agarose gel electrophoresis, DNA content analysis
      and the terminal deoxytransferase (TdT)-mediated dUTP nick end-labelling (TUNEL)
      method. DNA fragmentation and the hypodiploid fraction in the cell cycle were
      both increased in HSV-1-infected CD4 and CD8 lymphocytes stimulated with
      phytohaemagglutinin (PHA) compared to mock-infected lymphocytes. The percentage
      of cells in the S phase was decreased in HSV-1-infected CD4 and CD8 lymphocytes.
      HSV-1 antigen, glycoprotein D (gD) and regulatory protein ICP27 were detected in
      8-18% of the hypodiploid fraction of PHA-stimulated, HSV-1-infected lymphocytes.
      Apoptosis was induced not only in HSV-1 antigen-expressing cells but also in
      cells not expressing detectable viral proteins. Addition of anti-Fas antibody,
      anti-Fas-ligand antibody or a mixture of both had no effect on HSV-1-induced
      apoptosis, indicating that the Fas-Fas-ligand pathway did not contribute to HSV-1
      induced apoptosis.

PMID- 9266997
TI  - Nitric oxide production induced by herpes simplex virus type 1 does not alter the
      course of the infection in human monocytic cells.
AB  - Undifferentiated U937 cells were not susceptible to herpes simplex virus type 1
      (HSV-1) infection, but after differentiation with phorbol 12-myristate 13-acetate
      an increase in the permissivity to the virus was observed accompanied by the
      production of significant levels of viral particles. High levels of nitric oxide
      (NO) were produced in differentiated U937 cells infected with HSV-1. This
      production was comparable to that observed after addition of the NO donor
      glycerine trinitrate. The levels of NO drastically decreased when the cells were
      incubated with L-monomethyl arginine (L-NMA), an inhibitor of NO synthase.
      Although similar levels of NO were sufficient to decrease susceptibility of U937
      cells to other viruses, neither incubation with NO donors nor addition of L-NMA
      altered the permissiveness to HSV-1 infection. Thus, these results suggest that
      NO does not interfere with the replication of HSV-1 in U937 cells.

PMID- 9266998
TI  - The human cytomegalovirus glycoprotein B gene (ORF UL55) is expressed early in
      the infectious cycle.
AB  - Northern hybridizations were carried out using mRNA preparations of human
      cytomegalovirus (HCMV)-infected cultures and gene-specific antisense RNA probes
      for transcriptional analysis of the gene cluster composed of genes for DNA
      polymerase, glycoprotein B (gB), herpes simplex virus-infected cell protein 18.5
      homologue p130 and a major DNA-binding protein corresponding to open reading
      frames (ORFs) UL54-UL57, respectively. Monocistronic transcripts of 5 kb and 3.7
      kb were found for ORFs UL54 and UL55, respectively, and five additional high
      molecular mass overlapping transcripts of 14 kb, 10 kb, 10 kb, 8 kb and 6 kb were
      found. Mapping of 5' ends showed that transcription was initiated at the expected
      distance downstream of predicted TATA elements; in the case of a UL56-specific
      transcript two potential initiation sites were identified. Transcription was
      found to terminate at the expected distance downstream of either of two prominent
      polyadenylation consensus motifs in the region of UL54. All transcripts were
      identified early in the infectious cycle, except for the UL55 (gB)-specific
      transcript of 3.7 kb which was not synthesized until late post-infection.
      However, specific immunoreactions demonstrated the presence of a gB-specific
      polypeptide early after infection in the absence of viral DNA synthesis. It is
      suggested that a bicistronic transcript of 8 kb encoded by ORFs UL55 and UL54 is
      involved in biosynthesis of early HCMV gB.

PMID- 9266999
TI  - Human cytomegalovirus infection results in altered Cdk2 subcellular localization.
AB  - Human cytomegalovirus (HCMV) stimulates numerous cellular pathways upon
      infection. One of these pathways involves activation of cyclin E/Cdk2. Recent
      reports have demonstrated that Cdk2 is retained in the cytoplasm of cells
      arrested in GO by serum deprivation, sequestered from its regulatory subunit
      cyclin E which is located within the nucleus. Cdk2 rapidly enters the nucleus and
      becomes active upon stimulation of these cells with serum growth factors. The
      ability of HCMV to activate cyclin E/Cdk2 in both serum-arrested cells and
      contact-inhibited cells suggests that HCMV infection may also result in the
      translocation of Cdk2 into the nucleus. In this report, we demonstrate that Cdk2
      is sequestered in the cytoplasm of cells arrested in GO by contact inhibition, as
      well as those arrested by serum deprivation. HCMV infection results in
      translocation of Cdk2 from the cytoplasm into the nucleus within 24 h of
      infection, both in serum-arrested and contact-inhibited cells.

PMID- 9267000
TI  - Identification of the gene coding for rhesus cytomegalovirus glycoprotein B and
      immunological analysis of the protein.
AB  - The nucleotide sequence of the gene encoding glycoprotein B (gB) of rhesus
      cytomegalovirus (RhCMV) was determined and the protein characterized. The open
      reading frame of gB encoded a protein of 854 amino acids with 60% identity and
      75% similarity at the amino acid level to human cytomegalovirus (HCMV) gB.
      Cysteine residues in the extraluminal part of the protein are perfectly
      conserved. Out of the 16 potential N-linked glycosylation sites present in HCMV
      gB, 15 are conserved in RhCMV gB. Immunoblot analyses with antisera detected
      three bands of 150 kDa, 90-110 kDa and 55 kDa representing the full-length gB as
      well as the proteolytic cleavage products. Cross-reactivity and cross
      neutralization of a number of HCMV gB-specific monoclonal antibodies with RhCMV
      gB indicated sharing of immunogenic epitopes between the two molecules. The RhCMV
      gB regions corresponding to antigenic domains AD-1, 2 and 3 of HCMV gB were
      immunogenic during natural RhCMV infection with the AD-1 region being the
      immunodominant domain. The data indicate that RhCMV might represent a useful
      model to investigate pathogenesis and immune surveillance of cytomegaloviruses.

PMID- 9267001
TI  - Cloning and characterization of rhesus cytomegalovirus glycoprotein B.
AB  - Rhesus cytomegalovirus (RhCMV) infection of rhesus macaques is an important model
      to investigate critical issues of cytomegalovirus biology. To better understand
      host immunological responses to viral glycoproteins, the glycoprotein B (gB) gene
      of RhCMV was molecularly cloned, sequenced and characterized. Transcription
      analysis revealed that RhCMV gB was transcribed as a late gene. The RhCMV gB gene
      encoded a predicted protein of 854 amino acids that was 60% identical/75% similar
      to the human CMV (HCMV) gB protein. The region of HCMV gB proposed to be
      responsible for virus binding to host cells, fusion and cell-to-cell spread was
      the most highly conserved region with RhCMV gB (74% identity/85% similarity).
      Conserved elements included 11 of 12 cysteine residues, 14 of 16 potential N
      linked glycosylation sites and cross-reactive epitopes. Metabolic labelling
      experiments demonstrated that RhCMV gB was proteolytically processed similarly to
      HCMV gB. These results are critical for investigating virus-host relationships in
      CMV-infected primates.

PMID- 9267002
TI  - Analysis of the biochemical properties of, and complex formation between,
      glycoproteins H and L of the gamma2 herpesvirus bovine herpesvirus-4.
AB  - Genes encoding glycoprotein gH and gL homologues were localized in the genome of
      the gamma-herpesvirus bovine herpesvirus-4 (BHV-4). Both genes were sequenced and
      glutathione S-transferase fusion proteins were produced and used to immunize
      rabbits against the translation products of the two genes. The anti-gH serum
      recognized a protein with an apparent molecular mass (MM) of 110 kDa both in
      infected cells and in virions. This protein was sensitive to endo-beta-N
      acetylglucosaminase-H (endoH) and endoglycosidase F-N-glycosidase F (endoF
      PNGaseF) digestion. A protein with the same relative mobility was
      immunoprecipitated from infected cells radiolabelled with [3H]glucosamine which
      confirmed that this product (gp110), now designated BHV-4 gH, was glycosylated.
      Western blotting with the anti-gL serum detected in infected cells a product with
      an apparent MM ranging from 31-35 kDa and diffusely migrating protein species
      ranging from 45-65 kDa. Tunicamycin, monensin, endoH or endoF-PNGaseF treatments
      showed that both the 31-35 kDa and the 45-65 kDa proteins were glycosylated, gp31
      35 being a precursor of the 45-65 kDa glycoprotein species. In
      radioimmunoprecipitation assays, the anti-gL serum immunoprecipitated from
      infected cells two glycosylated proteins with apparent MMs of 31-35 kDa (gp31-35)
      and 45-55 kDa (gp45-55). However a third glycoprotein, gp110, was also
      immunoprecipitated together with gp31-35 and gp45-55. gp110 and gp45-55 were
      subsequently confirmed to be virion glycoproteins corresponding to mature forms
      of BHV-4 gH and gL respectively. In addition, the present study clearly
      demonstrated complex formation between BHV-4 gH and gL both in virions and in
      infected cells.

PMID- 9267003
TI  - Immunological control of murine gammaherpesvirus infection is independent of
      perforin.
AB  - Perforin-mediated cytotoxic T cell killing has been suggested to be of importance
      in the control of noncytopathic virus infections, based on studies with
      lymphocytic choriomeningitis virus (LCMV). We examined the role of perforin in a
      mouse model of gammaherpesvirus infection using transgenic perforin-deficient
      mice. Previous work from this laboratory has shown that CD8 T cells are essential
      for the resolution of the acute lung infection and control of latently infected B
      cells in murine gamma-herpesvirus 68 infection. The absence of perforin did not
      significantly affect the kinetics of either the lytic lung infection or the
      latent spleen infection. Lymphocytes from both perforin-deficient and control
      mice secreted comparable levels of IFN-gamma, IL-10 and IL-6. In addition,
      lymphocytes from both strains had similar levels of CD3epsilon-dependent
      cytotoxic activity in the spleen, draining lymph nodes and bronchoalveolar
      lavage. These data indicate that the lack of perforin has little affect on the
      ability of mice to control an experimental gammaherpesvirus infection.

PMID- 9267004
TI  - Epstein-Barr virus-encoded LMP-1 protein upregulates the pNDCF group of
      nucleoskeleton-cytoskeleton-associated proteins.
AB  - In a recent study, we described a group of monoclonal antibodies that identify
      five high molecular mass proteins which associate with intermediate filaments in
      the cytoplasm and accumulate in nuclear foci as well. The proteins have been
      designated pNDCFs, proteins associated with nuclear dots and cytoplasmic
      filaments. Their expression in human B cells was upregulated by Epstein-Barr
      virus (EBV) infection or by exposure to anti-CD40 antibodies and IL4.
      Phenotypically representative (type I) Burkitt's lymphoma (BL) cell lines do not
      express pNDCFs or, if they do, the proteins accumulate preferentially in nuclear
      dots. Type III BL cell lines that have drifted to a more immunoblastic phenotype
      during in vitro passage and EBV-transformed lymphoblastoid cell lines (LCLs) of
      non-neoplastic origin express these proteins regularly at high levels. They are
      preferentially but not exclusively associated with vimentin filaments in the
      cytoplasm. Here we show that all five pNDCFs can be upregulated by expressing the
      EBV-encoded membrane protein LMP1 in type I BLs. Three of them could also be
      upregulated in the human keratinocyte cell line RHEK-1 by LMP1 transfection. This
      upregulation was paralleled by the LMP1-induced increase in vimentin expression
      in both cell types. One of the pNDCFs, detected by the MAb DM_4A6, accumulated in
      cap-like structures under the cell membrane that colocalized with membrane
      patches of LMP1, in addition to its localization in nuclear dots and in
      association with cytoplasmic vimentin filaments.

PMID- 9267005
TI  - Antibodies against vaccinia virus do not neutralize extracellular enveloped virus
      but prevent virus release from infected cells and comet formation.
AB  - Vaccinia virus (VV) produces two antigenically and structurally distinct
      infectious virions, intracellular mature virus (IMV) and extracellular enveloped
      virus (EEV). EEV is important for the efficient dissemination of virus both in
      vivo and in vitro where it causes formation of comet-shaped virus plaques. Here,
      we show that EEV, in contrast to IMV, is resistant to neutralization by
      antibodies bound to its surface. However, antibodies against EEV can prevent
      comet formation in cell culture. To explain this apparent paradox, we
      investigated the mechanism by which antibodies inhibit comet formation and
      demonstrated that antibodies prevent EEV release from infected cells, and
      consequently comet formation, by agglutination of the virus on the cell surface.
      Two complementary observations allow this conclusion: first, electron microscopy
      showed that infected cells incubated with medium containing anti-vaccinia virus
      antibodies have virus aggregates on their surface; second, culture medium from
      these cells contained a 4 log10 fold reduction in the physical particle/ml titre
      in comparison with control culture. A mechanism by which antibodies to EEV
      proteins provide immunological protection is thus restriction of EEV release
      rather than neutralization of free EEV particles.

PMID- 9267006
TI  - Mosaic hepatitis B virus core particles allow insertion of extended foreign
      protein segments.
AB  - Because of its particular immunological properties, the core protein of hepatitis
      B virus (HBcAg) has become one of the favoured 'virus-like particles' for use as
      a carrier of foreign epitopes. A new strategy to construct core particles
      presenting extended foreign protein segments was established based on the
      introduction of a linker containing a translational stop codon between sequences
      encoding a C-terminally truncated HBcAg (HBcAg delta) and a foreign protein
      sequence. Expression in an Escherichia coli suppressor strain allowed the
      simultaneous synthesis of both HBcAg delta and a read-through fusion protein
      containing a part of the hantavirus nucleocapsid protein. After purification, the
      presence of core-like mosaic particles with HBc and hantavirus antigenicity was
      demonstrated by electron microscopy and immunological tests. This strategy of
      partial stop codon suppression should improve the use of HBcAg as a carrier of
      foreign epitopes by allowing insertion of long foreign sequences into particle
      forming proteins. The resulting mosaic particles should be of general interest
      for further vaccine developments.

PMID- 9267007
TI  - Effects of a frequent double-nucleotide basal core promoter mutation and its
      putative single-nucleotide precursor mutations on hepatitis B virus gene
      expression and replication.
AB  - The basal core promoter (BCP) of hepatitis B virus (HBV) directs the
      transcription of both precore RNA and core RNA which code for e antigen (HBeAg)
      and core antigen, respectively. A double mutation in the BCP which converts
      nucleotide (nt) 1762 from A to T and nt 1764 from G to A is frequently observed
      in patients with chronic hepatitis B. We recently demonstrated that this double
      mutation prevented the binding of a liver-enriched factor (LEF) to the BCP,
      suppressed only precore RNA transcription (and hence HBeAg expression), and
      enhanced progeny virus production. In order to understand the mechanism for the
      selection of this frequent double mutation, we have extended our previous studies
      to further characterize LEF and to compare the effects of this double-nucleotide
      mutation (M1) with each single-nucleotide mutation at nt 1762 (M2) and nt 1764
      (M3). Our results indicate that LEF is likely composed of a heterodimer formed
      between the transcription factor chicken ovalbumin upstream promoter
      transcription factor (COUP-TF) and an unidentified liver-enriched factor. Further
      studies reveal that both M1 and M2 prevent the binding of LEF to the BCP,
      suppress only precore RNA transcription, and increase the efficiency of progeny
      virus synthesis. In contrast, M3 retains some LEF binding activity, does not
      suppress HBV RNA transcription, and reduces slightly the efficiency of virus
      progeny synthesis. The reduced ability of M3 to replicate indicates that it has
      no selection advantage in itself at the level of the infected hepatocyte. In
      spite of its enhanced replication rate, M2 is rarely detected in HBV patients.
      This indicates the involvement of factors other than intracellular replication
      rates in the selection of these virus variants in the infected individual.

PMID- 9267008
TI  - Complete genome structure and phylogenetic analysis of little cherry virus, a
      mealybug-transmissible closterovirus.
AB  - The 5'-terminal genomic region (8597 nt) of little cherry virus (LChV), a
      mealybug-borne closterovirus, was cloned from double-stranded RNA, and its
      sequence determined to complete the 16934 nt sequence of the monopartite LChV RNA
      genome. In the 5' to 3' direction, the sequence encompasses ORF 1a, encoding the
      conserved replicative domains of methyltransferase and helicase, and ORF 1b,
      encoding RNA polymerase. ORFs 1a and 1b partially overlap (in O/+1
      configuration), and the LChV replicase is probably expressed by ribosomal
      frameshifting as a fusion product with a molecular mass of 318 kDa. The N
      terminal part of the ORF 1a product contains a papain-like cysteine proteinase
      (PCP) domain with a predicted cleavage site between Gly-619 and Ser-620. The PCP
      and the upstream protein domains can be aligned with the equivalent parts of the
      leader proteins encoded by the whitefly-transmitted lettuce infectious yellows
      and sweet potato sunken vein closteroviruses. Phylogenetic reconstruction based
      on the aligned RNA polymerase sequences clearly suggests that the aphid
      transmissible and whitefly-transmissible closteroviruses represent two distinct
      evolutionary lineages, with the mealybug-transmissible LChV being the most remote
      member of the 'whitefly' lineage.

PMID- 9267009
TI  - Characterization of epitopes on zucchini yellow mosaic potyvirus coat protein
      permits studies on the interactions between strains.
AB  - Monoclonal antibodies (MAbs) raised against the coat protein of zucchini yellow
      mosaic potyvirus (ZYMV) were characterized by epitope mapping using synthetic
      oligopeptides. Two mutant viruses with a mutation in the amino acid sequence
      important for epitope recognition in vitro were obtained by site-directed
      mutagenesis of a full-length cDNA of ZYMV. Two MAbs, CC11 and DD2, could
      distinguish specifically between these mutants in mixed infections, or after
      sequential inoculations of muskmelons. Sequential inoculations of the mutants and
      analysis with MAbs CC11 and DD2 revealed that cross-protection was established
      between these quasi-isogenic strains within 48 h.

PMID- 9267010
TI  - Complementation of a potato virus X mutant mediated by bombardment of plant
      tissues with cloned viral movement protein genes.
AB  - Microprojectile bombardment was used to examine the transport function of the 25
      kDa movement protein (MP) encoded in the triple gene block of potato virus X
      (PVX). A 25 kDa MP-defective full-length cloned PVX genome carrying a beta
      glucuronidase (GUS) reporter gene was co-bombarded with 35S promoter constructs
      containing either the 25 kDa MP gene of wild-type PVX, the MP gene of either of
      two tobamoviruses (tomato mosaic virus or crucifer tobamovirus), red clover
      necrotic mosaic dianthovirus (RCNMV) or brome mosaic bromovirus (BMV). When
      inoculated alone, the MP-defective PVX was unable to move out of the inoculated
      cell, as visualized by in situ staining for GUS activity. However, cell-to-cell
      movement of the mutant PVX genome was restored by co-inoculation with 35S
      constructs containing the MP cDNA of PVX, either tobamovirus or RCNMV. The BMV MP
      construct did not complement movement of the defective PVX. These results show
      that co-bombardment of cDNA of an MP-defective virus with plasmids designed to
      express MP of other viruses could be used as a fast and simple method for
      transcomplementation experiments.

PMID- 9267011
TI  - Replication of in vitro tobravirus recombinants shows that the specificity of
      template recognition is determined by 5' non-coding but not 3' non-coding
      sequences.
AB  - Natural recombinant tobacco rattle tobravirus (TRV) isolates contain sequences
      from a different tobravirus, pea early browning virus (PEBV). To characterize the
      sequence requirements for viable recombinant formation hybrid cDNA clones of RNA2
      of PEBV and TRV were assembled. Inclusion of 320 nt from the 5' terminus of PEBV
      or 335 nt from the 5' terminus of TRV in the hybrid RNAs was sufficient to permit
      their replication by, respectively, PEBV RNA1 or TRV RNA1 regardless of the
      origin of the 3' terminal region. However, PEBV RNA1 but not TRV RNA1 was
      sometimes able to support low level replication of RNA2 containing the
      heterologous 5' terminal region. In vitro translation of PEBV transcripts
      containing 5' noncoding region deletions supported the hypothesis that in vivo
      the PEBV coat protein (CP) is expressed from a subgenomic RNA and that,
      therefore, in the recombinants the CP subgenomic promoter probably is recognized
      by the replicase of the heterologous virus.

PMID- 9267012
TI  - Tubule-forming capacity of the movement proteins of alfalfa mosaic virus and
      brome mosaic virus.
AB  - The structural phenotype of the movement proteins (MPs) of two representatives of
      the Bromoviridae, alfalfa mosaic virus (AMV) and brome mosaic virus (BMV), was
      studied in protoplasts. Immunofluorescence microscopy showed that the MPs of
      these viruses, for which there has been no evidence of a tubule-guided mechanism,
      assemble into long tubular structures at the surface of the infected protoplast.
      Electron microscopy and immunogold analysis confirmed the presence of both MP and
      virus particles in the tubules induced by AMV and BMV. The significance of the
      tubule-forming properties of these viral MPs is discussed.

PMID- 9267013
TI  - Mapping of the RNA-binding domain of the cucumber mosaic virus movement protein.
AB  - A series of in-frame deletion mutants was used to identify a domain within the 3a
      protein of cucumber mosaic virus (CMV) that is required for RNA-binding activity.
      Deletions in the 3a gene were generated by PCR and restriction digestion, and the
      resulting mutated 3a sequences were cloned either in pT7-7 or in pGEX-5X3
      expression vectors. The mutated 3a proteins or fusions with glutathione S
      transferase (GST) were expressed in E. coli, purified, and their nucleic acid
      binding activities analysed by photochemical UV cross-linking assays using
      digoxigenin-UTP-labelled RNA probes. Comparative analyses of seven mutated 3a
      proteins obtained from inclusion bodies and eight GST fusion proteins revealed
      that there is an RNA-binding domain located between amino acids 174 and 233. This
      RNA-binding domain is able to bind single-stranded RNA out of the context of the
      complete 3a movement protein and is highly conserved within both subgroups of
      CMV.

PMID- 9267014
TI  - Evidence that DNA-A of a geminivirus associated with severe cassava mosaic
      disease in Uganda has arisen by interspecific recombination.
AB  - Geminivirus isolates associated with the epidemic of severe cassava mosaic
      disease in Uganda were studied and compared with virus isolates from the part of
      Uganda outside the epidemic area, and with African cassava mosaic virus (ACMV)
      and East African cassava mosaic virus (EACMV). Isolates of a novel type [the
      Uganda variant (UgV)] were detected in severely affected plants from the epidemic
      area, whereas those from plants outside the epidemic area were typical of ACMV.
      The complete nucleotide sequences of DNA-A of UgV (2799 nt) and of a Tanzanian
      isolate of EACMV (2801 nt) were determined and are extremely similar, except for
      the coat protein (CP) gene. The CP gene of UgV has three distinct regions: the 5'
      219 nt are 99% identical to EACMV (only 79% to ACMV); the following 459 nt are
      99% identical to ACMV (75% to EACMV); and the 3' 93 nt are 98% identical to EACMV
      (76% to ACMV). UgV DNA-A therefore is considered to have arisen by interspecific
      recombination of EACMV and ACMV. Despite the hybrid nature of their CP, UgV
      isolates were indistinguishable from ACMV in tests with 20 monoclonal antibodies
      (MAbs), including seven which reacted with ACMV but not EACMV. The discontinuous
      epitopes detected by these seven MAbs must involve amino acids which lie in the
      central part of the CP (residues 74-226) and which differ in ACMV and EACMV. UgV
      isolates were detected in severely mosaic-affected plants from all 11 widely
      separated locations sampled. The probable role of recombination in geminivirus
      evolution in the short to medium term is discussed.

PMID- 9267015
TI  - Molecular characterization of a subgroup I geminivirus from a legume in South
      Africa.
AB  - A South African geminivirus for which we propose the name bean yellow dwarf virus
      (BeYDV) has been isolated from French bean (Phaseolus vulgaris cv. Bonus) showing
      stunting, chlorosis and leaf curl symptoms. A full-length cloned copy of the
      viral genome produced characteristic symptoms of the disease when reintroduced
      into French bean by agroinoculation, and was systemically infectious in Nicotiana
      benthamiana, N. tabacum, Lycopersicon esculentum, Datura stramonium and
      Arabidopsis thaliana. BeYDV resembles subgroup I geminiviruses which infect
      monocotyledonous plants in having a single DNA component, two non-overlapping
      virion-sense (V1 and V2) and two overlapping complementary-sense (C1 and C2)
      coding regions, and an intron within the complementary-sense coding regions that
      is excised to produce a C1C2 fusion protein. It is most closely related to
      tobacco yellow dwarf virus from Australia, the only subgroup I geminivirus
      previously known to infect dicotyledonous plants, although it is sufficiently
      dissimilar (65% nucleotide sequence identity) to be considered a distinct virus.

PMID- 9267016
TI  - The p10 gene of Spodoptera littoralis nucleopolyhedrovirus: nucleotide sequence,
      transcriptional analysis and unique gene organization in the p10 locus.
AB  - The p10 gene of the Spodoptera littoralis (Spli) multicapsid nucleopolyhedrovirus
      (MNPV) was identified. With a coding sequence of 315 nucleotides (nt),
      corresponding to a protein of 104 amino acids, the SpliMNPV p10 gene is the
      longest p10 gene known. This gene codes for a putative protein with an Mr of
      11130 and was found to be most closely related to the Spodoptera exigua (Se) MNPV
      p10 (49.4% amino acid identity) and most distant from the Autographa californica
      (Ac) MNPV p10 (20.0% amino acid identity). Characterization of the protein's
      secondary structure and a comparison with other p10 protein species suggested
      that this p10 has an extended alpha-helical domain with high probability of
      forming a large coiled-coil structure. The p10 mRNA was about 1500 nt long, as
      determined by Northern blot analysis. Primer extension assay mapped three
      transcription start sites to a conserved baculovirus late promoter motif, TAAG.
      In the SpliMNPV genome, the p10 gene is not flanked by genes similar to p26 and
      p74, as found in SeMNPV, AcMNPV, Choristoneura fumiferana MNPV and Orgyia
      pseudotsugata MNPV. Instead, an open reading frame (ORF) of 945 bp is located
      downstream from the p10 gene and is followed by another ORF in opposite
      orientation, encoding the p74 protein. Upstream of the p10 sequences, an ORF of
      552 bp was identified that potentially encodes a 184 amino acid protein of Mr
      20925, which showed 52.2% identity with the encoded product of the SeMNPV xb187
      gene.

PMID- 9267017
TI  - Cosuppression comes to the animals.

PMID- 9267018
TI  - CED-4--the third horseman of apoptosis.

PMID- 9267019
TI  - Nuclear receptors in Sicily: all in the famiglia.

PMID- 9267020
TI  - Unified nomenclature for Eph family receptors and their ligands, the ephrins. Eph
      Nomenclature Committee.

PMID- 9267021
TI  - Apaf-1, a human protein homologous to C. elegans CED-4, participates in
      cytochrome c-dependent activation of caspase-3.
AB  - We report here the purification and cDNA cloning of Apaf-1, a novel 130 kd
      protein from HeLa cell cytosol that participates in the cytochrome c-dependent
      activation of caspase-3. The NH2-terminal 85 amino acids of Apaf-1 show 21%
      identity and 53% similarity to the NH2-terminal prodomain of the Caenorhabditis
      elegans caspase, CED-3. This is followed by 320 amino acids that show 22%
      identity and 48% similarity to CED-4, a protein that is believed to initiate
      apoptosis in C. elegans. The COOH-terminal region of Apaf-1 comprises multiple WD
      repeats, which are proposed to mediate protein-protein interactions. Cytochrome c
      binds to Apaf-1, an event that may trigger the activation of caspase-3, leading
      to apoptosis.

PMID- 9267022
TI  - Cell type-specific phosphorylation and proteolysis of a transcriptional regulator
      controls the G1-to-S transition in a bacterial cell cycle.
AB  - The global transcriptional regulator CtrA controls multiple events in the
      Caulobacter cell cycle, including the initiation of DNA replication, DNA
      methylation, cell division, and flagellar biogenesis. CtrA is a member of the
      response regulator family of two component signal transduction systems and is
      activated by phosphorylation. We report here that this phosphorylation signal
      enters the cell cycle at mid S phase. In addition, CtrA function is modulated by
      temporally and spatially controlled proteolysis. When an active CtrA protein is
      present at the wrong time in the cell cycle, owing to expression of a mutant CtrA
      derivative that is active in the absence of phosphorylation and is not turned
      over during the cell cycle, the G1-to-S transition is blocked and the cell cycle
      aborts. Thus, both phosphorylation and proteolysis are critical determinants of
      bacterial cell cycle control in a manner that is analogous to the control of the
      eukaryotic cell cycle.

PMID- 9267023
TI  - Dynamic changes of BRCA1 subnuclear location and phosphorylation state are
      initiated by DNA damage.
AB  - BRCA1 localizes to discrete nuclear foci (dots) during S phase. Hydroxyurea
      mediated DNA synthesis arrest of S phase MCF7 cells led to a loss of BRCA1 from
      these structures. Ultraviolet light, mitomycin C, or gamma irradiation produced a
      similar effect but with no concurrent arrest of DNA synthesis. BARD1 and Rad51,
      two proteins associated with the BRCA1 dots, behaved similarly. Loss of the BRCA1
      foci was accompanied by a specific, dose-dependent change(s) in the state of
      BRCA1 phosphorylation. Three distinct DNA damaging agents preferentially induced
      this change in S phase. The S phase BRCA1 phosphorylation response to DNA damage
      occurred in cells lacking, respectively, two DNA damage-sensing protein kinases,
      DNA-PK and Atm, implying that neither plays a prime role in this process.
      Finally, after BRCA1 dot dispersal, BRCA1, BARD1, and Rad51 accumulated, focally,
      on PCNA+ replication structures, implying an interaction of BRCA1/BARD1/Rad51
      containing complexes with damaged, replicating DNA. Taken together, the data
      imply that the BRCA1 S phase foci are dynamic physiological elements, responsive
      to DNA damage, and that BRCA1-containing multiprotein complexes participate in a
      replication checkpoint response.

PMID- 9267024
TI  - Inscuteable and Staufen mediate asymmetric localization and segregation of
      prospero RNA during Drosophila neuroblast cell divisions.
AB  - When neuroblasts divide, inscuteable acts to coordinate protein localization and
      mitotic spindle orientation, ensuring that asymmetrically localized determinants
      like Prospero partition into one progeny. staufen encodes a dsRNA-binding protein
      implicated in mRNA transport in oocytes. We demonstrate that prospero RNA is also
      asymmetrically localized and partitioned during neuroblast cell divisions, a
      process requiring both inscuteable and staufen. Inscuteable and Staufen interact
      and colocalize with prospero RNA on the apical cortex of interphase neuroblasts.
      Staufen binds prospero RNA in its 3'UTR. Our findings suggest that Inscuteable
      nucleates an apical complex and is required for protein localization, spindle
      orientation, and RNA localization. Stau, as one component of this complex, is
      required only for RNA localization. Hence staufen also acts zygotically,
      downstream of inscuteable, to effect aspects of neuroblast asymmetry.

PMID- 9267025
TI  - Miranda is required for the asymmetric localization of Prospero during mitosis in
      Drosophila.
AB  - Asymmetric division of Drosophila neuroblasts, sensory organ precursor cells, and
      cells in the procephalic neurogenic region involves the segregation of Numb and
      Prospero proteins into one of the two daughter cells. We have isolated a novel
      gene, miranda, based on the ability of its gene product to interact with the
      Prospero asymmetric localization domain. miranda expression coincides spatially
      and temporally with asymmetric cell divisions and asymmetric localization of
      Prospero. Miranda protein is localized asymmetrically, along with Prospero, to
      the basal cell membrane during mitosis. Loss of miranda gene function abolishes
      asymmetric Prospero localization during mitosis. The asymmetric localization of
      Miranda protein requires inscuteable. Our results suggest that miranda functions
      downstream of inscuteable and works as an adapter that connects Prospero to the
      basal cell membrane during asymmetric cell division.

PMID- 9267026
TI  - PHYL acts to down-regulate TTK88, a transcriptional repressor of neuronal cell
      fates, by a SINA-dependent mechanism.
AB  - We show that Tramtrack (TTK88) expression represses neuronal fate determination
      in the developing Drosophila eye. Phyllopod (PHYL) acts to antagonize this
      repression by a mechanism that requires Seven In Absentia (SINA) and is
      associated with decreased TTK88 protein levels, but not reduced ttk88 gene
      transcription or mRNA stability. We present evidence that SINA, PHYL, and TTK88
      physically interact and that SINA interacts genetically and physically with
      UBCD1, a component of the ubiquitin-dependent protein degradation pathway. Our
      results suggest a model in which activation of the Sevenless receptor tyrosine
      kinase induces PHYL expression, which then acts with SINA to target the
      transcriptional repressor TTK88 for degradation, thereby promoting R7 cell fate
      specification.

PMID- 9267027
TI  - Photoreceptor cell differentiation requires regulated proteolysis of the
      transcriptional repressor Tramtrack.
AB  - The transcription repressor Tramtrack (TTK) is found in cone cells but not
      photoreceptor cells of the Drosophila eye. We show that down-regulation of TTK
      expression occurs in photoreceptor cells and is required for their fate
      determination. Down-regulation requires the presence of Phyllopod (PHYL), which
      is induced by the RAS pathway, and Seven In Absentia (SINA). Loss of either gene
      causes accumulation of TTK in photoreceptor cells, and TTK does not accumulate in
      cone cells if both PHYL and SINA are present. We report that SINA and PHYL
      promote ubiquitination and rapid degradation of TTK by the proteasome pathway in
      cell culture, and both SINA and PHYL bind to the N-terminal domain of TTK. These
      results argue that photoreceptor differentiation is regulated by the RAS pathway
      through targeted proteolysis of the TTK repressor.

PMID- 9267028
TI  - Cosuppression in Drosophila: gene silencing of Alcohol dehydrogenase by white-Adh
      transgenes is Polycomb dependent.
AB  - When two to six copies of a white promoter-Alcohol dehydrogenase (Adh) reporter
      fusion gene are introduced into the genome, the expression is progressively
      reduced both in larvae and adults rather than the expected gene dosage effect. In
      addition, multiple transgenes reduce endogenous Adh transcripts, a result that is
      strongly analogous to "cosuppression" phenomena described in many plant species
      but which has not been previously observed in animals. Silencing of the Adh gene
      is not influenced by zeste-dependent transvection but strongly affected by the
      Polycomb and Polycomblike mutations. Polycomb and polyhomeotic proteins are bound
      to the chromatin at the sites of the repressed w-Adh transgenes.

PMID- 9267029
TI  - In vivo observation of polypeptide flux through the bacterial chaperonin system.
AB  - The quantitative contribution of chaperonin GroEL to protein folding in E. coli
      was analyzed. A diverse set of newly synthesized polypeptides, predominantly
      between 10-55 kDa, interacts with GroEL, accounting for 10%-15% of all
      cytoplasmic protein under normal growth conditions, and for 30% or more upon
      exposure to heat stress. Most proteins leave GroEL rapidly within 10-30 s. We
      distinguish three classes of substrate proteins: (I) proteins with a chaperonin
      independent folding pathway; (II) proteins, more than 50% of total, with an
      intermediate chaperonin dependence for which normally only a small fraction
      transits GroEL; and (III) a set of highly chaperonin-dependent proteins, many of
      which dissociate slowly from GroEL and probably require sequestration of
      aggregation-sensitive intermediates within the GroEL cavity for successful
      folding.

PMID- 9267030
TI  - A tyrosine-based signal targets H/K-ATPase to a regulated compartment and is
      required for the cessation of gastric acid secretion.
AB  - Gastric acid secretion is mediated by the H/K-ATPase of parietal cells.
      Activation of acid secretion involves insertion of H/K-ATPase into the parietal
      cell plasmalemma, while its cessation is associated with reinternalization of the
      H/K-ATPase into an intracellular storage compartment. The cytoplasmic tail of the
      H/K-ATPase beta subunit includes a four residue sequence homologous to tyrosine
      based endocytosis signals. We generated transgenic mice expressing H/K-ATPase
      beta subunit in which this motif's tyrosine residue is mutated to alanine.
      Gastric glands from animals expressing mutant beta subunit constitutively secrete
      acid and continuously express H/K-ATPase at their cell surfaces. Thus, the beta
      subunit's tyrosine-based signal is required for the internalization of H/K-ATPase
      and for the termination of acid secretion. As a consequence of chronic
      hyperacidity, the mice develop gastric ulcers and a hypertrophic gastropathy
      resembling Menetrier's disease.

PMID- 9267031
TI  - TRAP is necessary for gliding motility and infectivity of plasmodium sporozoites.
AB  - Many protozoans of the phylum Apicomplexa are invasive parasites that exhibit a
      substrate-dependent gliding motility. Plasmodium (malaria) sporozoites, the stage
      of the parasite that invades the salivary glands of the mosquito vector and the
      liver of the vertebrate host, express a surface protein called thrombospondin
      related anonymous protein (TRAP) that has homologs in other Apicomplexa. By gene
      targeting in a rodent Plasmodium, we demonstrate that TRAP is critical for
      sporozoite infection of the mosquito salivary glands and the rat liver, and is
      essential for sporozoite gliding motility in vitro. This suggests that in
      Plasmodium sporozoites, and likely in other Apicomplexa, gliding locomotion and
      cell invasion have a common molecular basis.

PMID- 9267032
TI  - Structure and conformational changes in NSF and its membrane receptor complexes
      visualized by quick-freeze/deep-etch electron microscopy.
AB  - Using quick-freeze/deep-etch electron microscopy of recombinant proteins adsorbed
      to mica, we show that NSF, the oligomeric ATPase involved in membrane fusion, is
      a hollow 10 x 16 nm cylinder whose conformation depends upon nucleotide binding.
      Depleted of nucleotide, NSF converts to a "splayed" protease-sensitive
      conformation that reveals its subunit composition. NSF's synaptic membrane
      substrate, the ternary SNARE complex containing syntaxin, SNAP-25, and
      synaptobrevin, is a 4 x 14 nm rod with a "tail" at one end, corresponding to the
      N-terminus of syntaxin. Using epitope tags, antibodies, and maltose-binding
      protein markers, we find that syntaxin and synaptobrevin are aligned in parallel
      in the complex, with their membrane anchors located at the same end of the rod.
      This SNARE rod binds with alpha-SNAP to one end of the NSF cylinder to form an
      asymmetric "20S" complex. Together, these images suggest how NSF could dissociate
      the SNARE complex and how association and dissociation of the complex could be
      related to membrane fusion.

PMID- 9267033
TI  - Formation of neuronal intranuclear inclusions underlies the neurological
      dysfunction in mice transgenic for the HD mutation.
AB  - Huntington's disease (HD) is one of an increasing number of human
      neurodegenerative disorders caused by a CAG/polyglutamine-repeat expansion. The
      mutation occurs in a gene of unknown function that is expressed in a wide range
      of tissues. The molecular mechanism responsible for the delayed onset, selective
      pattern of neuropathology, and cell death observed in HD has not been described.
      We have observed that mice transgenic for exon 1 of the human HD gene carrying
      (CAG)115 to (CAG)156 repeat expansions develop pronounced neuronal intranuclear
      inclusions, containing the proteins huntingtin and ubiquitin, prior to developing
      a neurological phenotype. The appearance in transgenic mice of these inclusions,
      followed by characteristic morphological change within neuronal nuclei, is
      strikingly similar to nuclear abnormalities observed in biopsy material from HD
      patients.

PMID- 9267034
TI  - Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates
      in vitro and in vivo.
AB  - The mechanism by which an elongated polyglutamine sequence causes
      neurodegeneration in Huntington's disease (HD) is unknown. In this study, we show
      that the proteolytic cleavage of a GST-huntingtin fusion protein leads to the
      formation of insoluble high molecular weight protein aggregates only when the
      polyglutamine expansion is in the pathogenic range. Electron micrographs of these
      aggregates revealed a fibrillar or ribbon-like morphology, reminiscent of scrapie
      prions and beta-amyloid fibrils in Alzheimer's disease. Subcellular fractionation
      and ultrastructural techniques showed the in vivo presence of these structures in
      the brains of mice transgenic for the HD mutation. Our in vitro model will aid in
      an eventual understanding of the molecular pathology of HD and the development of
      preventative strategies.

PMID- 9267035
TI  - Termination of mammalian rDNA replication: polar arrest of replication fork
      movement by transcription termination factor TTF-I.
AB  - A replication fork barrier (RFB) at the 3' end of eukaryotic ribosomal RNA genes
      blocks bidirectional fork progression and limits DNA replication to the same
      direction as transcription. We have reproduced the RFB in vitro in HeLa cell
      extracts using 3' terminal murine rDNA fused to an SV40 origin-based vector. The
      RFB is polar and modularly organized, requiring both the Sal box transcription
      terminator and specific flanking sequences. Mutations within the terminator
      element, depletion of the RNA polymerase I-specific transcription termination
      factor TTF-I, or deletion of the termination domain of TTF-I abolishes RFB
      activity. Thus, the same factor that blocks elongating RNA polymerase I prevents
      head-on collision between the DNA replication apparatus and the transcription
      machinery.

PMID- 9267038
TI  - Pinealocyte ultrastructure in mutant mice that lack sympathetic innervation to
      the pineal gland.
AB  - Pinealocyte synaptic ribbons (SR) and dense-cored vesicles (DCV) were quantitated
      in mice that have developmental deficiencies in the sympathetic innervation of
      the pineal gland due to a null mutation for the p75 low-affinity NGF receptor
      (NGFR). SR exhibited a significant increase whereas there was a significant
      decline in the frequency of DCV in mutant mice. These findings support the
      hypothesis that pinealocyte SR and DCV are regulated by neural mechanisms
      associated with sympathetic system. Ultrastructural characteristics of
      pinealocytes in mutants included degenerative changes that culminated in the
      breakdown of cellular components and the accumulation of flocculent-containing
      vesicles within the cytoplasm. Ribosomal lamellar complexes were also commonly
      seen in pinealocytes of mutant rats. Although the mutant pineal gland exhibited
      signs of metabolic imbalances, the cytoarchitecture of the gland (e.g., vascular
      compartment) and differentiation of the cells were generally unaffected by
      developmental deficiencies in the gland's innervation.

PMID- 9267037
TI  - In vivo vascular damage, leukocyte activation and inflammatory response induced
      by beta-amyloid.
AB  - beta-amyloid toxicity is central to the pathology of Alzheimer's disease. Recent
      evidence implicates vascular dysfunction as a contributing factor to the dementia
      of Alzheimer type. Using intravital microscopy we demonstrate that in vivo
      administration of beta-amyloid produces extensive vascular disruption including
      endothelial and smooth muscle damage, adhesion and migration of leukocytes across
      arteries and venules. Amyloid angiopathy with vascular damage and inflammatory
      changes are hallmarks in the brains of Alzheimer disease victims. The vascular
      actions of beta-amyloid are distinct from the neurotoxic properties of the
      peptide and were prevented by the free radical scavenging enzyme superoxide
      dismutase. Oxygen radical mediated vascular dysfunction may induce ischemic and
      inflammatory responses leading to neurodegeneration as seen in Alzheimer's
      disease.

PMID- 9267039
TI  - Atypical cilia in testicular cells from normal rats.
AB  - During our observations solitary cilia have been noted in Sertoli cells,
      fibroblasts and myoid cells of the rat testes. They mostly presented a 9 + 0
      pattern and appeared similar to those previously reported in other cell types. In
      the present report, we describe their structure and analyze their putative
      functional significance.

PMID- 9267036
TI  - Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms
      a multimeric activation complex with P/CAF and CBP/p300.
AB  - We report here the identification of a novel cofactor, ACTR, that directly binds
      nuclear receptors and stimulates their transcriptional activities in a hormone
      dependent fashion. ACTR also recruits two other nuclear factors, CBP and P/CAF,
      and thus plays a central role in creating a multisubunit coactivator complex. In
      addition, and unexpectedly, we show that purified ACTR is a potent histone
      acetyltransferase and appears to define a distinct evolutionary branch to this
      recently described family. Thus, hormonal activation by nuclear receptors
      involves the mutual recruitment of at least three classes of histone
      acetyltransferases that may act cooperatively as an enzymatic unit to reverse the
      effects of histone deacetylase shown to be part of the nuclear receptor
      corepressor complex.

PMID- 9267041
TI  - Microvascular pathology in the skeletal muscle paraneoplastic phenomenon.
AB  - An electron microscopic investigation was made in order to study capillary
      alterations in the muscle paraneoplastic phenomenon associated with different
      malignant tumours. Several abnormalities were found including basement membrane
      widening and lamination, endothelial hypertrophy, a varied degree of lumen
      occlusion, and proliferative changes in pericytes. A degenerative process leading
      to capillary necrosis was also observed. A mononuclear cell infiltrate formed by
      macrophages, lymphocytes and mast cells was seen. The capillary changes observed
      suggest the existence of an autoimmune vascular factor in the etiopathogenesis of
      muscle damage in this phenomenon.

PMID- 9267040
TI  - The effect of ACE inhibitors on atheroma formation is potentiated by association
      with a calcium channel blocker. A biochemical and ultrastructural study.
AB  - The effect of two angiotensin converting enzyme (ACE) inhibitors, enalapril
      maleate and captopril, on the progression of atherosclerosis was investigated.
      Golden Syrian hamsters were divided into five groups: controls (C), fed a
      standard chow diet; hypercholesterolemic animals (HH) induced by supplementing
      the diet with 3% cholesterol and 15% butter; HH treated with enalapril (20
      mg/kg/day); HH treated with captopril (60 mg/kg/day) and HH treated
      simultaneously with enalapril and a calcium channel blocker, diltiazem (45
      mg/kg/day). The drugs were administered for one month, concomitantly with the
      atherogenic diet. As compared to controls, in HH group a significant increase in
      serum cholesterol (approximately 5 fold) and ACE activity (approximately 3 fold)
      was found. In HH-treated animals, both drugs maintained the serum ACE activity
      within the normal values. However, the effect upon serum cholesterol was
      different: enalapril and its combination with diltiazem had a significant
      hypocholesterolemic effect (128.8 +/- 25 mg/dl), whereas captopril had no effect
      on the cholesterol values (326.6 +/- 41.48 mg/dl). Electron microscopical
      examination of the coronary arteries and aortic valve in all experimental groups
      indicated a good correlation between the high levels of cholesterol, ACE activity
      and the development of the atherosclerotic lesions. Captopril treatment inhibits
      the early phases of atherosclerosis at level of the coronary artery but has no
      influence upon the lesion development in the aortic valve. By comparison,
      enalapril and enalapril-diltiazem co-administration impede the development of
      fatty streaks by decreasing the accumulation of lipids and calcium deposits in
      the lesion-prone areas examined. These data indicate that: 1) captopril does not
      have a hypocholesterolemic potential and cannot prevent atheroma formation in
      heart valves; 2) enalapril, especially combined with diltiazem, has a
      hypocholesterolemic effect and impedes the development of atheromatous plaque; 3)
      the anti-atherosclerosis therapy may benefit from the co-administration of an ACE
      inhibitor with a calcium antagonist.

PMID- 9267043
TI  - Characterization of melanosomes and melanogenesis in cells cultured from Ota's
      nevus.
AB  - Cells from dermis and epidermis of Ota's nevus lesions were cultured to obtain
      the pigment producing cells that are specific epidermal and dermal melanocytes of
      nevus Ota. The following media were used: Eagle's minimum essential medium,
      fortified or not fortified with cholera toxin and phorbol ester. Both epidermal
      melanocytes and dermal melanocytes grew in the Eagle's minimum essential medium
      fortified with cholera toxin and phorbol ester. The melanocytes were
      characterized by 14C-tyrosine uptake and by identification of melanosomes and
      status of melanogenesis in comparison with those reported in dysplastic nevi and
      melanomas, as well as those found in Ota's nevus tissue in situ. Eumelanosomes,
      pheomelanosomes and secondary lysosomal melanosomes appeared in epidermal
      melanocytes. Pheomelanosomes and melanolysosomes, or myelinosiderosomes appeared
      predominantly in the dermal melanocytes. These melanosomes seemed to be related
      to the peculiar skin color of nevus Ota. Some of the abnormal types of
      melanosomes were very similar to those found in dysplastic nevi and melanomas.

PMID- 9267042
TI  - A rare association of myasthenia gravis and mitochondrial myopathy: a clinical,
      biochemical and morphologic study of one case.
AB  - Myasthenia gravis and mitochondrial myopathy may present with similar clinical
      symptoms as inconstant palpebral ptosis, ophthalmoparesis, and muscle weakness. A
      few case initially diagnosed as myasthenia gravis by a positive decremental
      response on EMG and successful anticholinesterase therapy revealed to be affected
      by mitochondrial disease. We report a new case initially found to be affected by
      myasthenia gravis in whom muscle biopsy, performed because of symptom worsening,
      disclosed a mitochondrial myopathy. It is not clear if the association of
      mitochondrial myopathy and myasthenia gravis is coincidental or if there is a
      pathogenic link between the two pathologies. We suggest that muscle biopsy should
      be performed in cases with atypical myasthenia gravis signs.

PMID- 9267044
TI  - Regional differentiation of the blood-epididymis barrier in stallion (Equus
      caballus).
AB  - The occurrence, localization and ultrastructural characteristics of a blood
      tissue barrier throughout the stallion proximal seminal excurrent duct system
      were studied by the exclusion of electron-dense tracers and freeze-fracture
      techniques. Striking differences were observed in the distribution of lanthanum
      tracer and in the geometrical organization of the zonulae occludentes along the
      ductus efferentes, epididymides and vas deferens. The zonulae occludentes domain,
      the principal structural component of the blood-epididymis barrier, differed in
      permeability, width and strand numbers along the ductus. The flow of tracer was
      not impeded by the vascular endothelium, the peritubular myoid layer or other
      surface membrane specialization. The tight junctions of the ductuli efferentes
      are poorly developed but unlike those of rats, guinea pigs or man they are not
      associated with gap junctions. The result of the tracer experiments and the low
      number of tight junctional strands in the ductuli efferentes suggests that the
      barrier of the ductuli efferentes corresponds to the 'leaky type'. In the
      epididymis the zonulae occludentes are well developed throughout the duct. The
      greatest number of strands, especially in the cauda epididymidis regions,
      correlates well with a decreased junctional permeability in this area. Another
      evidence for the existence of the stallion blood-epididymis barrier are the
      differences in the proteins electrophoretic profiles between blood plasma as
      compared with the fluid inside the seminal ductus. This junctional complexes
      contribute to create a highly defined luminal fluid microenvironment that ensures
      the sperm maturation and survival.

PMID- 9267045
TI  - Glucose transporter GLUT1 in human brain microvessels revealed by ultrastructural
      immunocytochemistry.
AB  - The brain glucose transporter GLUT1 is a transmembrane glycoprotein belonging to
      the glucose carrier family comprising five isoforms characterized by different
      functional properties and tissue specificity. Biochemical and immunohistochemical
      analyses have demonstrated that GLUT isoform 1 is localised within the brain
      microvascular endothelium, where it controls glucose uptake through the blood
      brain barrier (BBB). In this study the expression of GLUT1 was analysed by means
      of light and electron immunocytochemistry in the adult human cerebellar cortex.
      The glucose transporter is strongly expressed in cerebellum microvessels, and is
      localised not only within endothelial cells but also in microvascular pericytes.
      Moreover, some glial expression of GLUT1 was observed in the neutrophil and in
      perivascular glial sheaths. The observations demonstrate that different cellular
      types are involved in the control of brain glucose homeostasis by GLUT1
      expression at the BBB site, and support the postulated highly specialised role of
      brain microvascular pericytes.

PMID- 9267046
TI  - Interaction between cytolytic T-cells and immobilized renal tubular epithelial
      cells: evidence of polarity on both effector and target cells.
AB  - The mode by which cytolytic T-lymphocytes (CTL) deliver the lethal hit to their
      targets has been studied extensively. The CTL exhibits a characteristic
      polarization, with the attacking end formed by the uropod (containing the Golgi
      complex and associated granules). The effect on the target cell (TC) has been
      considered as a form of apoptosis or of both necrosis. In this communication we
      describe the particular morphological steps that relate to the participation of
      the target renal epithelial cell to its own destruction. Thus, the TC forms tight
      membrane contacts with the CTL that are invested by a dense network of stress
      fibers and microtubules within the TC cytoplasm in a manner similar to the areas
      of attachment between the epithelial cells or of the latter to the underlying
      surface. The TC mitochondria at the site of the CTL attachment are markedly
      swollen, in contrast to the more distally located ones that appear initially
      normal. The TC plasma membrane surrounding the CTL attachment site shows focally
      intense blebbing. In later stages, associated with overt apoptosis, global TC
      blebbing is present. In summary, the TC shows a polarization pattern, that
      corresponds roughly to the polarity exhibited by the attacking cell (uropod
      protopod), and to some degree treats the latter cell as a junctional partner.

PMID- 9267047
TI  - Submicroscopic mathematical evaluation of spermatozoa in assisted reproduction.
      3. Partial zona dissection (PZD) (Notulae seminologicae 12).
AB  - This paper belongs to a series of application of the Baccetti's et al. (1995)
      formula to the submicroscopical mathematical examination of the human spermatozoa
      used for assisted reproduction. The present experiment concerns partial zona
      dissection, a technique requiring a careful evaluation of sperm quality in order
      to predict the success of the program. Our results demonstrate that the sperm
      submicroscopic characters introduced in the formula are clearly correlated with
      the result of PZD. In fact the two numbers concerning the sperm ultrastructural
      quality (percentage and total number of spermatozoa free from defects in the
      ejaculate) obtained in successful and unsuccessful PZD groups, showed a large
      difference (P < 0.01). The most important characteristics seem to be the quality
      of the acrosomal complex, the condition of the chromatin and the mitochondrial
      assembly. All these characteristics are expressed with largely different means in
      successful and unsuccessful ejaculates (from P < 0.05 to P < 0.01). A comparison
      with the results previously obtained in ICSI (Strehler et al., 1995) and IVF
      (Piomboni et al., 1996) shows that sperm quality is significantly more implicated
      in the success of IVF than of PZD or ICSI.

PMID- 9267048
TI  - Morphologic changes in the vesical transition epithelium of alcoholic rats.
AB  - Few studies are available about the effect of alcohol on the epithelium of the
      urinary bladder. In the present investigation we studied the ultrastructure of
      the vesical transition epithelium of normal rats and of rats submitted to
      experimental chronic alcoholism. Adult rats were submitted to experimental
      chronic alcoholism by the ingestion of sugar cane liquor. The vesical epithelium
      was examined after 60, 120, 180 and 240 days of alcohol treatment by transmission
      electron microscopy. Surface cells presented nuclear and cytoplasmic changes and
      marked cellular desquamation. There was an increase in multivesicular bodies and
      lysosomes suggesting cell degeneration. Mast cell infiltration was observed,
      possibly related to increased epithelial sensitivity. Intracellular spaces were
      frequently observed. The transmission epithelium of the urinary bladder was found
      to be sensitive to the action of alcohol, as demonstrated by the changes in the
      components of the blood-urine barrier, the greater sensitivity to inflammation,
      the increase in cell desquamation and the greater recycling of the apical
      membrane and of the fusiform vesicles of surface cells observed in alcoholic
      rats.

PMID- 9267049
TI  - Unique crystalline inclusions in neonatal pig small intestine epithelial cells.
AB  - In this study we describe the presence of novel crystalline inclusions in the
      jejunal and ileal epithelium of newborn pigs. Hampshire/Yorkshire piglets (0-3
      days) were anesthetized with pentobarbital and tissues were recovered following
      laparotomy. Sections of jejunum and ileum were prepared with a variety of
      fixatives for paraffin and methacrylate embedment for the light and electron
      microscopy. The characteristics of these crystalline structures have been
      demonstrated by cytochemical staining, immunohistochemical staining, and
      ultrastructural studies. Using light microscopy, it was determined that 10.8% of
      villus epithelial cells in the jejunum contained inclusions, whereas inclusions
      were present in 26.6% of the villus epithelial cells in the ileum. Inclusions
      were absent in crypt epithelial cells of both areas of the intestine, and the
      percentage of cells with inclusions increased towards the villus tip. Preliminary
      histochemical analysis has been unrevealing. The inclusions are periodic
      acid/Schiff's (PAS) reagent-negative, and do not stain for the presence of
      concentrated proteins. Using electron microscopy, the inclusions are found to be
      clustered in the supra-nuclear region of the cells and are generally oriented
      with the long axis of the cell. The crystals vary in size and have a dense core
      region surrounded by a regular less dense periphery.

PMID- 9267050
TI  - Supplementation of aspartate, asparagine and carnitine in the diet causes marked
      changes in the ultrastructure of soleus muscle.
AB  - The effects of the supplementation of aspartic acid and asparagine (45 mg.kg1
      body weight of each), and carnitine (90 mg.kg-1 body weight) during one week on
      the ultrastructure of soleus muscle from swimming-trained (five weeks) and
      sedentary rats were examined. In trained rats, the amino acids supplementation
      was performed during the last week of the exercise training only. Supplementation
      of these amino acids in the diet either in sedentary and trained rats caused
      myofibrillar and mitochondrial disorganization and dissolution. Focal
      degeneration of myofibrils and Z-line streaming and disruption, as well as
      internalization of nuclei were observed. The size of mitochondria increased and
      some of them presented severe swelling, with decreased electron-density of the
      matrix and disruption of internal and external membranes. The changes in the
      soleus muscle ultrastructure described do suggest functional disorders. This
      observation is particularly important for the amino acid intakers and deserves to
      be further investigated.

PMID- 9267051
TI  - Immunolocalization of several laminin chains in the normal human central and
      peripheral nervous system.
AB  - Using specific monoclonal antibodies against different subunits of laminin, we
      studied the differential distribution pattern of several laminin chains in the
      central (CNS) and peripheral (PNS) nervous system. Laminin chains alpha 1, beta 1
      and gamma 1, were found in the basement membrane (BM) of blood vessels in both
      CNS and PNS. In contrast, laminin alpha 2 though present in the BM of capillaries
      in the CNS, was completely absent from PNS capillaries. Laminins alpha 2, beta 1,
      gamma 1 could be detected in peripheral nerve, in the BM of Schwann cells, which
      did not contain Laminin alpha 1. The possible importance of laminin alpha 2 for
      myelination in the PNS as well as in the function of the blood-brain barrier in
      the CNS, and its potential relevance to the pathology of congenital muscular
      dystrophy associated with deficiency of this laminin chain, is discussed.

PMID- 9267052
TI  - Sweat gland vacuoles in Unverricht-Lundborg disease.
AB  - We report a re-evaluation of skin biopsies of 4 patients with Unverricht-Lundborg
      (UL) disease showing membrane-bound bodies in sweat glands. The previously
      described findings in 5 patients by Cochius et al. (1994) are confirmed. The data
      suggest that skin biopsy may be a useful mean for confirmation of diagnosis in
      this disorder, but the specificity of these findings is to be proved by
      examination of a larger number of cases.

PMID- 9267053
TI  - Cytomegalovirus in the parotid gland of a slow loris, Nyctecibus coucang.
AB  - Sporadic enlarged cells with both nuclear and cytoplasmic viruses were found in
      the intralobular ducts of the parotid salivary gland of an adult female slow
      loris; these ducts are homologous to striated ducts in the salivary glands of
      other primates. The duct cell nuclei contained reticular inclusions and virions
      in all stages of development. Cytoplasmic virions were, in almost every case,
      confined to vacuoles; only a very few were free in the cytosol. The viruses
      conformed in ultrastructure to that of cytomegaloviruses described in other
      species. This may be the first observation by electron microscopy of in situ
      cytomegaloviruses in the salivary glands of a nonhuman primate.

PMID- 9267054
TI  - The need for immunisation--lessons from history.

PMID- 9267055
TI  - Mefloquine prophylaxis--revisited.

PMID- 9267056
TI  - New advances and horizons in immunisation.
AB  - Scientific and technological advances will make it possible within the next
      decade to vaccinate against a number of infectious diseases for which hitherto no
      active immunisation has been available. This article considers what vaccines are
      likely to be licensed for use in the next decade and the possible indications for
      their use. Combination vaccines that provide protection against a greater number
      of diseases while not increasing the number of visits or injections per visit
      will be an important feature of expanding the infant vaccination schedule. The
      article also considers vaccines that will become available for adolescents and
      adults as well as progress in vaccine development to protect against diseases
      such as hepatitis C, human immunodeficiency virus (HIV) and tuberculosis.

PMID- 9267057
TI  - Immunising the population. Are we succeeding?
AB  - While diseases such as diphtheria and poliomyelitis have disappeared in this
      country, other vaccine preventable diseases such as measles, pertussis and
      rubella are quite common and result in epidemics from time to time. There are
      some groups in the community with particularly low coverage with specific
      vaccines and they need extra attention. Immunisation providers need to identify
      the barriers to achieving high coverage rates and adopt measures to overcome
      these barriers.

PMID- 9267058
TI  - Prevention of hepatitis A and B.
AB  - The vaccine preventable hepatitides, hepatitis A and hepatitis B, cause a great
      burden of illness in both developing and industrialized nations. There is
      increased community awareness of the problems of viral hepatitis, and it is
      important for general practitioners to be aware of current recommendations for
      prevention of hepatitis A and B.

PMID- 9267059
TI  - Pneumococcal vaccine.
AB  - Pneumococcal infection is a major health problem in both developed and developing
      countries. Adult patients with a range of chronic illnesses are at increased risk
      of both morbidity and mortality from this condition. The currently available 23
      valent vaccine is generally not effective in children under 2 years of age or
      adults with significant immunosuppression. However, case control and cohort
      studies have established the vaccine's effectiveness in patients with a number of
      chronic illnesses as well as those undergoing splenectomy. The vaccine is safe
      and should be more widely used by practitioners with patients who meet the
      current NHMRC guidelines.

PMID- 9267060
TI  - Cholera and typhoid vaccine. The current state of play.
AB  - The field of travel medicine is undergoing rapid change. Vaccination
      recommendations change with disease outbreaks, emerging infections and the
      availability of new vaccines. The following information on typhoid and cholera
      vaccination should be used in conjunction with up to date information and
      individualised for each traveller. It is emphasised that vaccination forms just
      part of the pretravel health consultation and does not replace the need for
      appropriate preventive advice and information.

PMID- 9267061
TI  - Treating common nail problems.
AB  - This article is a follow up to the article There is something wrong with my nail
      (AFP, June 1997). Conditions of the nail often pose diagnostic and management
      problems. The former issues were addressed in the previous article while this
      article focuses on current management options for this difficult range of
      conditions.

PMID- 9267062
TI  - Monitoring glucose control.
AB  - Type 2 diabetes is increasing in prevalence and is predominantly managed in
      general practice. This series contains case histories raising some of the
      metabolic problems which may be encountered in the management of these patients
      and indicates some of the many issues, other than glycaemic control, that need to
      be considered.

PMID- 9267063
TI  - Headache and testicular pain.
AB  - A 40 year old architect presents to you with severe headache and testicular pain.
      He has been unwell for several days with illness that started with influenzal
      type symptoms with a mild pharyngitis and myalgias. His headache has become
      increasingly more severe in the past 36 hours and is occipital in location. His
      testicular pain has become more intense in the past 24 hours. Examination
      discloses a temperature of 38.2 degrees C and moderate meningism. There are no
      focal neurological signs. His right testis is exquisitely tender to palpation. He
      has had no significant past history of note.

PMID- 9267064
TI  - Tales from a home visiting doctor.

PMID- 9267065
TI  - The causes of rhabdomyolysis.

PMID- 9267066
TI  - Is ramipril anti-arrhythmic?

PMID- 9267067
TI  - Coding in general practice.

PMID- 9267068
TI  - Salmonella java phage type Worksop in young children associated with fresh
      fortified milk.

PMID- 9267069
TI  - Bacteremia and bacterial meningitis in England and Wales: 1982 to 1996.

PMID- 9267070
TI  - An outbreak of Salmonella hadar phage type 5 infection in London.

PMID- 9267071
TI  - Two outbreaks of Vero cytotoxin producing Escherichia coli O157 infection
      associated with farms.

PMID- 9267072
TI  - AIDS and HIV infection in the United Kingdom: monthly report.

PMID- 9267073
TI  - Elevation of serum soluble interleukin-2 receptor levels in patients with
      hepatitis C virus infection.
AB  - To determine serum soluble interleukin-2 receptor (sIL-2 R) levels in hepatitis C
      virus (HCV) infection, serum sIL-2 R was measured in 260 subjects with chronic
      HCV infection, including 100 patients who had previously been treated with
      natural interferon (IFN) alpha, and in 51 HCV RNA-negative controls. Serum sIL-2
      R levels in asymptomatic HCV carriers, patients with chronic hepatitis, liver
      cirrhosis, and hepatocellular carcinoma (HCC) were significantly higher than
      those of healthy controls and subjects who were positive for anti-HCV and
      negative for HCV RNA (P < 0.01, respectively). Moreover, serum sIL-2 R levels
      were also significantly higher in patients with HCC than in other HCV RNA
      positive groups. There was some correlation between serum sIL-2 R levels and
      histological activity index scores (r = 0.287, P < 0.01) and serum alanine
      aminotransferase levels (r = 0.272, P < 0.01). In patients in whom HCV RNA was
      eliminated following IFN treatment, serum sIL-2 R levels decreased to those seen
      in healthy controls by one year post treatment. Serum sIL-2 R levels increase due
      to HCV infection, and the amount of increase corresponds to the degree of
      inflammation.

PMID- 9267074
TI  - Bilateral striate cortex contusion presenting with cerebral asthenopia rather
      than cortical blindness.
AB  - We report a 22-year-old female with a history of contusion of bilateral occipital
      lobes at the age of 1 year. Magnetic resonance imaging confirmed severe lesion in
      bilateral striate cortices which should have resulted in cortical blindness.
      However, she displayed a fairly good visual function presenting only cerebral
      asthenopia and the restriction of the visual field. A positron emission
      tomography revealed that no areas other than the primary visual cortices
      responded to visual stimuli. Thus, her residual vision may be attributable to
      plasticity of the visual cortex in humans.

PMID- 9267075
TI  - Piecing together the thymic puzzle.

PMID- 9267076
TI  - Nomenclature and characterization of leukocyte differentiation antigens in
      ruminants.

PMID- 9267077
TI  - Multiple sclerosis: variations on a theme.

PMID- 9267078
TI  - SCID: the role of adenosine deaminase deficiency.

PMID- 9267079
TI  - How does TAP associate with MHC class I molecules?

PMID- 9267080
TI  - B-cell superantigens.

PMID- 9267081
TI  - Th1-Th2: reliable paradigm or dangerous dogma?

PMID- 9267082
TI  - Non-receptor protein tyrosine kinases as immune targets of viruses.

PMID- 9267083
TI  - The role of Grb2-associated proteins in T-cell activation.

PMID- 9267084
TI  - Thymic involution.

PMID- 9267085
TI  - The challenge facing women in Irish general practice--rigidity despite
      flexibility.

PMID- 9267086
TI  - The management of hypercholesterolaemia.

PMID- 9267087
TI  - Vaccination guidelines and health precautions for travel abroad.

PMID- 9267088
TI  - Hospital infection control: expensive luxury or essential commodity?

PMID- 9267089
TI  - Wanted men.

PMID- 9267090
TI  - Experience of a rapid access acute chest pain clinic.
AB  - A descriptive follow-up study of a hospital based chest pain clinic set up for
      the identification of the patients with unstable angina and acute myocardial
      infarction. The clinic is staffed by a cardiologist-in-training seeing patients
      on the day of referral by general practitioners because of acute chest pain of
      unclear origin. Over 6 months, 174 patients were assessed. 34 (19.5%) had a
      diagnosis of unstable angina or acute myocardial infarction (acute coronary
      syndrome), 52 (30%) had non-acute cardia pain and 88 (50.5%) had non-cardiac
      pain. Of those with a clinical diagnosis of acute coronary syndrome, 5 were
      subsequently shown to have non-cardiac, 8 had acute myocardial infarction and 21
      had unstable angina. One month follow-up information was available on 136 of 139
      (98%) patients not admitted to hospital via the chest pain clinic. 3 were
      admitted to hospital within the following 4 weeks because of myocardial
      infarction in 1 and unstable angina in 2. One year follow-up was available on 118
      patients. One patient was admitted with unstable angina 6 months later and one
      patient sustained sudden cardiac death 3 months later. In the absence of the
      clinic, general practitioners would have arranged hospital admission for 66 (48%)
      or assessment in the emergency department for 13 (9%) of those discharged. Almost
      all general practitioners found the service helpful. The chest pain clinic was
      well received and provided an efficient method of identifying patients with acute
      coronary syndrome and minimised unnecessary admissions.

PMID- 9267091
TI  - Eye screening in the elderly.
AB  - Poor vision is considered to be a common unreported illness in the elderly
      population. To determine its prevalence we carried out an eye screen on 150
      randomly selected co-operative elderly subjects attending St James's Hospital. A
      database [mean age 78.2 years (range 65 to 97)], medical history, mini-mental
      test score [mean score 9.1 (range 2 to 10)], mobility assessment and history of
      eye problems was gathered. A visual test of both eyes together (standard N6 and
      N8), inspection of the eyes, tonometry (Perkin's handheld tonometer) and
      fundoscopy were performed on each subject and the need and reason for referral to
      an optician or an ophthalmologist was documented. Results show that 64% of
      subjects could read N6 or N8. Tonometry revealed no subject with raised
      intraocular pressure, including 4 subjects who were currently on treatment for
      glaucoma. Fundoscopy showed that 57.3% of subjects had some evidence of
      cataracts, 16.6% moderate and 3% severe. The retina appeared normal in 58.6% of
      subjects, 20.6% of the population had hypertensive changes, 4.6% had diabetic
      changes, 3% had optic atrophy, 1.3% had macular degeneration and a further 10%
      could not be clearly visualised due to cataracts. 90% of subjects wore glasses
      and the average duration since the glasses were last changed was 3.7 years (range
      2 weeks to 20 years). No glasses examined were in need of cleaning or repair. 36%
      of subjects could not read N8 (28 of these had forgotten their glasses and were
      advised to visit their optician if they could not read newsprint). 7.3% of
      subjects were referred to an optician for new glasses, 1.3% were referred to an
      ophthalmologist for newly diagnosed cataracts and 6.6% were regular attenders to
      an ophthalmologist. We conclude that the rate of new referrals for the occurrence
      of correctable undetected visual acuity deficit was lower than expected at 8.6%
      of subjects screened.

PMID- 9267092
TI  - Incidental neck symptoms in high energy trauma victims.
AB  - We conducted a prospective study into the incidence of neck symptoms in victims
      of high energy trauma. Thirty consecutive patients were questioned regarding neck
      and jaw pain and stiffness initially and at six weeks. Despite suffering
      extensive skeletal injuries as a result of road traffic accidents, only two
      patients had such symptoms. We conclude that the incidence of 'whip lash' is
      surprisingly low in victims of high energy trauma.

PMID- 9267093
TI  - Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes
      (MELAS) in a Donegal kindred--clinical features and molecular genetic analysis.
AB  - A 19 year old female with a background history of migraine, sensorineural
      deafness and recent personality change developed a parieto-occipital cerebral
      infarct. Investigations revealed altered lactate to pyruvate ratios, ragged red
      fibres in muscle and an A-G point mutation at position 3243 in mitochondrial DNA.
      Subsequent clinical and molecular genetic analysis of 14 family members in three
      generations identified 12 affected individuals, two of whom were asymptomatic.
      Maternal inheritance was confirmed. MEALS is an important but under recognised
      cause of stroke and seizures in the young. There is insufficient data available
      to determine if the treatment of asymptomatic individuals retards the onset or
      reduces the severity of stroke.

PMID- 9267094
TI  - Low rate of generic prescribing in the Republic of Ireland compared to England
      and Northern Ireland: prescribers' concerns.
AB  - We compared the level of generic prescribing in the Republic of Ireland, Northern
      Ireland and England and surveyed the views of Irish College of General
      Practitioners members. In 1993, generic drugs (pure generics and branded generics
      together) comprised 17.4% of total dispensing in the General Medical Services
      Scheme, significantly less than Northern Ireland or England where pure generics
      alone comprised 25% and 38% respectively of total dispensing in the National
      Health Services. General practitioners accurately self-estimated their level of
      generic prescribing but are concerned about the reliability/quality of generic
      products on the market, possible legal liabilities associated with their use and
      the fact that pharmacists may legally dispense more expensive proprietary
      preparations in the case of private prescriptions written generically.
      Prescribers need reassurance regarding legal and quality assurance aspects of
      generic prescribing if the level of generic drug use is to increase.

PMID- 9267095
TI  - Reversible pulmonary hypertension in neonatal Graves disease.
AB  - Neonatal thyrotoxicosis may occur by transplacental transfer of thyroid
      stimulating immunoglobins from the mother. Although the clinical manifestations
      may vary in the new-born period, hyperthyroidism has been associated with several
      cardiac complications including supraventricular tachycardia, cardiomyopathy and
      congestive cardiac failure. We report the case of a nine day old baby who
      presented with severe pulmonary hypertension in association with congestive
      cardiac failure secondary to neonatal thyrotoxicosis. Treatment of the heart
      failure and restoration of the thyroid function resulted in complete regression
      of the pulmonary hypertension. The recognition and reversibility of pulmonary
      hypertension in neonatal Graves disease has not been previously described.

PMID- 9267096
TI  - The prevalence of chemical substance and alcohol abuse in an obstetric population
      in Dublin.
AB  - OBJECTIVE: To determine the prevalence of illicit drug abuse and alcohol use in
      an obstetric population based in an urban maternity hospital. SETTING: A
      collaborative study between the Rotunda Hospital, Dublin and the Irish National
      Drug Advisory & Treatment Centre. DESIGN: A prospective study consisting of
      anonymous, unlinked urine testing of 504 'first visit' antenatal patients and a
      separate group of 515 patients six weeks after delivery. METHODS & OUTCOME
      MEASURES: Toxicological screening using enzyme-linked immunoassay techniques,
      with all positive samples being reanalysed. Drug histories were taken and samples
      were tested for alcohol and six of the most commonly abused drugs. The pre- and
      postnatal prevalence of abuse was matched with demographic data. RESULTS: The
      prevalence of chemical substance misuse in the antenatal population was 2.8% and
      5.6% in the postnatal population. Substances identified included benzodiazepines,
      cannabis, amphetamines, opiates and cocaine. Less than 2% of samples tested
      positive for alcohol. None of the women yielding positive samples had been pre
      identified on the basis of history. A significant proportion of the women were in
      the high risk categories with regard to age and socio-economic status.
      CONCLUSION: The prevalence of drug misuse antenatally was nearly 3% and
      postnatally almost 6%. Substance abusers in pregnancy are more likely to be
      single, unemployed, and to have had a previous pregnancy.

PMID- 9267097
TI  - Non-tuberculous mycobacterial infection of the parotid gland.
AB  - The case of a non-tuberculous mycobacterial infection of the parotid gland,
      presenting in a 15 year old female, is described. The patient presented with a
      six week history of a rapidly expanding, discrete parotid mass. Definitive
      management involved surgical removal of the mass by superficial parotidectomy.
      Current investigation and management of nontuberculous mycobacterial infections
      of the parotid gland is reviewed.

PMID- 9267098
TI  - Apathetic thyrotoxicosis.

PMID- 9267099
TI  - Tropical pyomyositis presenting as sciatica in Wicklow.

PMID- 9267100
TI  - Serzone superior to Prozac.

PMID- 9267101
TI  - Taxotere becomes first drug to outperform Adriamycin.

PMID- 9267102
TI  - Apoptosis is induced by anti-Fas antibody alone in cultured human keratinocytes.
AB  - Fas is a well-known cell surface receptor whose main function is the induction of
      apoptosis in many cell types including human keratinocytes. Several reports
      indicate that anti-Fas antibody can induce apoptosis in cultured keratinocytes
      after interferon gamma (IFN gamma) pretreatment. Because IFN gamma is synthesized
      by activated T cells, but not by keratinocytes, these results suggest that Fas
      may only be effective in apoptosis occurring in T-cell mediated inflammatory skin
      diseases. We hypothesized that Fas alone might mediate apoptosis in normal human
      keratinocytes without any other help and thus play a role in normal epidermal
      homeostasis. By using Cell Death Detection ELISA, we observed keratinocyte
      apoptosis 24 hours after anti-Fas antibody stimulation not only in IFN gamma
      pretreated conditions but also in non-pretreated conditions. Even though the
      percentage of cultured keratinocytes stained by anti-Fas antibody increased from
      7.8 to 25.8% 24 hours after IFN gamma stimulation, the apoptotic rate of the anti
      Fas only group was the same as that of the anti-Fas plus IFN gamma treated group.
      In both conditions, we have verified apoptotic phenomena in cultured
      keratinocytes in situ by TUNEL staining. Some apoptotic bodies were phagocytosed
      by neighboring keratinocytes. Fas-mediated apoptosis was not inhibited by the
      protein synthesis inhibitor cycloheximide and was enhanced by inhibitors of
      several protein kinases, including PKC and staurosporine. These results suggest
      that Fas-mediated apoptosis may play a role in both T cell-mediated skin diseases
      and normal epidermal homeostasis.

PMID- 9267104
TI  - Ultrastructural study of anti-tumor effects of tamoxifen in two malignant
      melanoma patients.
AB  - In order to clarify the mode of action (tumor cell death) of tamoxifen in
      treatment for estrogen receptor (ER) negative malignant melanoma, we administered
      the usual adult dose (20 mg/day) or a low dose, 1/4 of the usual dose (5 mg/day),
      of tamoxifen for 2 months to 2 male patients and investigated ultrastructural
      changes in their melanoma cells from metastatic lesions before and after the
      treatment. After the 2-month administration, metastatic nodules in both patients
      were reduced in size by approximately 50%. Histologically, their reduced nodules
      presented coagulation necrosis around the blood vessels. Electron microscopy of
      the necrosis revealed that melanoma cells were degenerated and disappeared;
      numerous aggregated melanosomes, free melanosomes, granular endoplasmic reticula,
      and lysosomes were present in the extracellular matrix and in the space between
      collagen fibers. The remaining melanoma cells had swollen cytoplasm and
      mitochondria with vacuolar changes. Cristae of mitochondria had disappeared.
      There was no infiltration of lymphocytes into the nodules. The organic changes of
      necrosis lesions were not observed. Because our two patients were ER negative,
      these effects of tamoxifen could be attributable to an action not mediated by ER.

PMID- 9267103
TI  - CD36 (OKM5) antigen expression on human mucosal epithelia is associated with
      keratinization type.
AB  - The glycoprotein CD36 functions as a thrombospondin receptor and is expressed on
      a variety of cell types, including platelets, monocyte/macrophages, and
      endothelial cells. In human skin, the presence of CD36 on keratinocytes was
      initially found in lesional areas of T-cell mediated inflammatory dermatoses.
      Controversy still exists on the interpretation of this expression as an
      inflammatory or differentiation-associated marker. So far, only limited data are
      available on CD36 expression in oral epithelia. The present immunohistochemical
      study was therefore performed to determine the presence of CD36 on keratinocytes
      of healthy and disease-affected epithelia of the oral cavity in 80 biopsy
      specimens. As results, we found an inflammation-independent strong expression of
      CD36 in oral epithelia with ortho- and parakeratinization, such as the oral side
      of the gingiva, the hard palate, and the back of the tongue. Non-keratinized
      epithelia such as the gingival pocket epithelium, the soft palate, the lip, the
      buccal mucosa, and the side of the tongue were CD36 negative. We therefore
      suggest that CD36 expression in keratinocytes from oral epithelia is an
      epithelial differentiation marker.

PMID- 9267105
TI  - Folliculosebaceous cystic hamartoma with a neural component: an
      immunohistochemical study.
AB  - We present a case of follicular cystic hamartoma, a distinctive cutaneous
      malformation characterized by marked overgrowth of folliculosebaceous units
      accompanied by appreciable mesenchymal alterations, including fibroplasia,
      increased vascular components, and numerous adipocytes. A conspicuous feature of
      our case is an aggregation of thick trespassing nerve bundles in the deep portion
      of the neoplasm. An immunohistochemical study revealed the nerve bundles were
      immunoreactive for the general neuronal marker protein gene product 9.5. The
      nerves, however, stained negatively with antibodies against neuropeptides such as
      calcitonin gene-related peptide, substance P, vasoactive intestinal polypeptide,
      and neuropeptide Y, all of which are known to be contained in normal cutaneous
      nerves. The presence of these aberrant nerve bundles devoid of the normal
      expression of neuropeptides supports the concept that folliculosebaceous cystic
      hamartoma is a true, tumor-like malformation characterized by abnormal overgrowth
      of normal components of the skin.

PMID- 9267106
TI  - Penicillamine-induced degenerative dermatoses: report of a case and brief review
      of such dermatoses.
AB  - We describe a case of elastosis perforans serpiginosa with additional findings of
      degenerative skin changes. A 20-year-old man with hepatolenticular degeneration,
      under prolonged treatment with D-penicillamine, presented with a circular or
      serpiginous arrangement of nuchal papules. Histopathologically, transepidermal
      channels were accompanied by granulomatous reactions, with several giant cells
      engulfing elastic fibers. In addition to these findings of a typical elastosis
      perforans serpiginosa, we observed scar-like skin changes inside the circular
      arrangement of the papules. At the scar-like tissue, we found electron
      microscopical evidence of randomly aggregated thin collagen fibers with no
      tendency toward systemic combined bundle formation, which is a characteristic
      feature of normal collagen fiber formation. Pseudoxanthoma-elasticum-like changes
      were observed on his neck. On his axillae and groin, slight skin thickening and
      wrinkling were detected. The diagnosis of elastosis perforans serpiginosa does
      not represent all of the manifestations or the pathological background described
      above. The skin manifestations described here represent not only an elastosis but
      also a total degenerative dermatosis with overhealed collagenosis. Thus, those
      dermatoses should be summarized as one entity, penicillamine-induced degenerative
      dermatosis. After considering the pathogenic background and clinical
      similarities, we further propose to simplify the penicillamine-induced skin
      manifestations to three categories: acute sensitivity reactions, bullous
      dermatoses, and degenerative dermatoses.

PMID- 9267107
TI  - Severe cutaneous and venous damage after DIC therapy.
AB  - A 79-year-old woman with skin ulcers caused by disseminated intravascular
      coagulation (DIC) therapy is reported. The patient had been treated by injection
      of drugs, including gabexate mesilate, into the right great saphenous vein. The
      maximum concentration of gabexate mesilate was calculated as 0.893%. Although the
      drugs did not extravasate, purpura initially appeared around the affected vein,
      followed by brown pigmentation with infiltration and ulcers with widely necrotic
      tissue from the middle portion of her thigh to the malleolus along her right
      great saphenous vein. As the ulcer showed no tendency to heal for more than 3
      months, surgical debridement and skin grafts were performed.

PMID- 9267108
TI  - A case of Paget's disease of the vulva recurring in a musculocutaneous flap.
AB  - A case of Paget's disease of the vulva which recurred in a reconstructed gracilis
      musculocutaneous flap without invasing adenocarcinoma is presented. The recurrent
      lesion was seen in the basal layer of the epidermis of the flap without invasion
      into the dermis. The possibility of an intraepidermal lateral invasion of Paget's
      cells into the epidermis of the flap is suggested.

PMID- 9267109
TI  - Pigmented epidermal cyst.
AB  - A 58-year-old Japanese woman with a pigmented epidermal cyst on the upper arch of
      the right external ear is described. The blue appearance of the cyst was striking
      and uncommon in Japanese. Histologically, abundant melanin pigment was observed
      in the keratinous mass of the cavity, and epithelial cells showed epidermoid
      keratinization. Increased numbers of melanocytes in the basal layer, large
      globular cells of melanocytic origin in the spinous layer, and hair-germ-like
      aggregates of basaloid cells and melanocytes were also observed. The blue
      clinical appearance is probably due to the rich melanin granules in the cyst,
      keratinous mass, keratinocytes, and hair-germ-like structures.

PMID- 9267110
TI  - Pincer nails and alopecia as markers of gastrointestinal malignancy.
AB  - Nail abnormalities may be markers of non-dermatologic disease. We present a case
      in which pronounced pincer nails and universal alopecia developed in association
      with a metastasising adenocarcinoma of the sigmoid colon. It is suggested that
      this association represents a new ectodermal paraneoplastic syndrome.

PMID- 9267111
TI  - Pneumomediastinum and subcutaneous emphysema associated with fatal interstitial
      pneumonia in dermatomyositis.
AB  - We described a 65-year-old woman who died of acute interstitial pneumonia
      associated with dermatomyositis. Subcutaneous emphysema and pneumomediastinum
      simultaneously developed. The association of the pulmonary rupture with
      vasculitis has been assumed as the common cause in interstitial pneumonia.
      Diffuse alveolar damage, however, might have led to the pneumomediastinum and
      subcutaneous emphysema in our patient, who had no signs of cutaneous vasculitis.

PMID- 9267112
TI  - Disseminated superficial porokeratosis in a patient with chronic liver disease.
AB  - A 55-year-old male suffering from liver cirrhosis presented with diffuse annular
      hyperkeratotic papules of abrupt onset on the trunk and extremities.
      Histopathologic examination revealed cornoid lamella and eosinophilic spongiosis.
      He did not receive any medications other than cephalosporin for spontaneous
      bacterial peritonitis. A review of the literature revealed that three cases
      developed porokeratosis when their liver function declined and that, in one case,
      the porokeratosis disappeared spontaneously with liver transplantation. Although
      the precise mechanism is unclear, there is evidence demonstrating
      immunoincompetence in cirrhosis. Even though we did not perform immunologic
      studies or exclude the possibility of drug-induced porokeratosis in our case, it
      is conceivable that porokeratosis can be triggered by immunosuppression due to
      liver cirrhosis per se.

PMID- 9267113
TI  - Degos' disease associated with rheumatoid arthritis.

PMID- 9267114
TI  - Striving toward a best practice model for a restraint-free environment.
AB  - Our aim at reducing seclusion and restraint started as a Department of Nursing
      quality indicator. The administration then made this program a hospital goal.
      Administrators and managers monitor this information daily and share it with
      various hospital quality improvement committees for review and subsequent
      practice changes. Although clinical settings may have slightly different
      definitions or approaches when addressing prevention, crisis intervention, and
      treatment, it is important to assess, reassess, and evaluate these patients at
      every step throughout the treatment process. We have found that the above
      interventions were successful in producing a major reduction in the use of
      restrictive interventions. The use of restraints does not help patients learn to
      manage their anger but only serves to control people and cause an immediate
      division between those seeking help and those who offer it. When patients are
      treated as people, with dignity and respect, they are less likely to become
      aggressive. As clinical settings strive to meet this challenge and eliminate the
      option of using these highly restrictive and sometimes punitive measures, ongoing
      administrative and clinical support in collaboration with patients, advocates,
      and others is essential. It is only through this means that traditional high-risk
      hands-on techniques will be replaced with new and innovative methods making the
      transition from ineffective outdated interventions to an effective best practice
      model.

PMID- 9267115
TI  - Health care accountability: communicating quality to the public.
AB  - For many years a revolution has been taking place in the area of health care
      accountability. Making those in health care accountable by evaluating their
      quality and then communicating that quality effectively to the public (purchasers
      and consumers) is a major task facing the industry today. This article provides
      an overview of current initiatives that are attempting to communicate quality to
      the public.

PMID- 9267116
TI  - Elements for a report card: one institution's experience moving from theory to
      trial.
AB  - The emerging computerized patient record, the movement toward a unified nursing
      language, and increasing accountability to the public for clinical outcomes are
      converging forces that require a coherent plan if nursing is to evaluate
      outcomes. The article describes a nursing service and school of nursing's
      approach and beginning experiences in identifying concepts and indicators that
      are useful to clinicians. These concepts and indicators have the potential to be
      embedded in a concurrent information system that would feed a data repository
      used retrospectively by clinicians and researchers. The article also discusses
      results to date and lessons learned.

PMID- 9267117
TI  - Dimensions and indicators of patients' perceived nursing care quality in the
      hospital setting.
AB  - Nursing professionals have noted the impact of cost-containment strategies on
      nursing care quality in the hospital setting. However, there is a lack of
      scientific data to demonstrate the impact. The author reviewed 53 published data
      based primary studies of patient satisfaction with nursing care (PSNC) from 1982
      to the present and identified 13 published PSNC instruments. The author performed
      content analysis of the published instruments and identified the dimensions and
      indicators of patients' perceived structure, process, and outcomes attributed to
      nursing care. The needs for further development of instruments to assess
      patients' perceived nursing care quality are identified.

PMID- 9267118
TI  - Health care consumer report cards: what do patients and families really want to
      know? What should they want to know?
AB  - Much attention has recently been focused on the health care industry's ability to
      demonstrate the quality of the services they provide. Health care provider
      organizations have begun to face growing demands for performance information from
      all sides, both within the industry (accrediting and regulating bodies) as well
      as from consumers. At present, the health care industry defines quality in three
      basic dimensions: (1) clinical quality, (2) service quality, and (3) customer
      satisfaction. Information is available to the public regarding performance due to
      partnerships of accrediting bodies and health care purchasers. This article
      explores what patients and families really want to know about their providers and
      health care facilities.

PMID- 9267119
TI  - Effect of standardized approach to the care of the extremely low birthweight
      infant.
AB  - An extremely low birthweight (ELBW) protocol was developed at this regional
      neonatal intensive care unit. The focus was the standardization of care related
      to the implementation/maintenance of a humidified environment and attention to
      prevention of skin excoriation in the extremely low birthweight infant (< 1000
      g). Steps toward successful implementation of the standardized approach required
      an interdisciplinary commitment, literature review of current practice
      methodologies, a definition of nursing and medical approach to these infants in
      the first days of life, and an evaluation of the practice change focusing on
      patient outcomes. A comparative review was completed that evaluated the change in
      patient outcomes of the extremely low birthweight infants relative to fluid and
      electrolyte status in the first five days of life after implementation of the
      protocol as compared to prior to implementation of the protocol.

PMID- 9267120
TI  - A survey of multicultural awareness among hospital and clinic staff.
AB  - Building a knowledgebase regarding multicultural beliefs and practices will help
      health care providers meet the challenge of caring for persons of diverse
      cultures. It is evident that developing greater multicultural awareness will also
      help health care workers improve patient care. For this reason, an
      Interdisciplinary Multicultural Patient Care Team (IMPACT) was developed at the
      University of Wisconsin Hospital and Clinics (UWHC) and UW Children's Hospital in
      1994. The IMPACT sought funds through the University of Wisconsin-Milwaukee
      Institute on Race and Ethnicity to conduct a hospital- and clinic-wide survey of
      its 4,000 full- and part-time employees regarding their understanding of
      multicultural issues. The goal of the survey was to expand upon the pilot study
      conducted in 1994 with the intent of ascertaining staff cultural awareness and
      educational needs. Over 800 multidisciplinary personnel returned the survey for a
      21 percent response rate. These data will be used to set up educational programs
      and develop a resource network for all personnel.

PMID- 9267122
TI  - [Compartment analysis of 123I-iomazenil brain on early and delayed SPECT].
AB  - We investigated the characteristics of 123I-Iomazenil (IMZ) SPECT images in 12
      adults (six males and six females, with a mean age of 56.1 years). The washout
      rate of 123I-IMZ from the brain was estimated from two SPECTs done 15 min and 3
      hr after injection. Although the washout was relatively slow, the rates differed
      in each intracerebral region, suggesting that the distribution of 123I-IMZ was
      gradually changing. Furthermore, assuming 123I-IMZ kinetics in the brain for the
      three-compartment, two-parameter model, the transition rate constant (K1) from
      the blood to the brain and the binding potentials (BP) of benzodiazepine to the
      receptor were calculated. The BP and K1 values were compared with 123I-IMZ SPECT
      counts and CBF values by 123I-IMP. The BP values correlated more closely with the
      counts on the delayed SPECT than those on the early SPECT. It was confirmed that
      delayed SPECT images reflect better the distribution of the benzodiazepine
      receptor than early images do. On the other hand, the K1 values correlated highly
      with CBF obtained by 123I-IMP, and this finding suggested that super-early SPECT
      images might be remarkably influenced by the distribution of CBF.

PMID- 9267124
TI  - [Improvement of a filter and the effect on the TECHNEGAS leakage].
AB  - We previously reported about the room air contamination during ventilation study
      using the TECHNEGAS system. Main cause of the contamination with radioactive gas
      were leakage through the filter and expiration of the patient after the
      inhalation. Then, a new type filter was developed to reduce the radioactive
      leakage. The efficacy and usefulness of the new type filter was examined. The
      radioactive leakage through the new filter was markedly reduced to 1/6 compared
      with the old type. But the air resistance of passage was increased over two times
      of the old type. This resistance is not able to disregard on respiratory
      physiology. Improvement to reduce the resistance is desirable.

PMID- 9267121
TI  - [Usefulness of 99mTc-tetrofosmin myocardial scintigraphy before and after
      coronary intervention].
AB  - Dipyridamole-loading 99mTc-tetrofosmin myocardial scintigraphy was performed for
      patients with coronary artery disease who underwent percutaneous transluminal
      coronary angioplasty (PTCA) in order to examine whether SPECT imaging prior to
      treatment is useful for the determination of prognosis after coronary
      intervention. Thirty-six patients including 9 with angina pectoris (AP), 22 with
      old myocardial infarction (OMI) and 5 OMI with AP were underwent dipyridamole
      loading 99mTc-tetrofosmin myocardial SPECT before and after coronary
      intervention. The length of follow-up was 185 +/- 107 days after PTCA.
      Improvement of myocardial uptake was observed on myocardial SPECT in all cases
      with AP. Improvement of the myocardial uptake was observed 50% (4/8) of patients
      with OMI who had no myocardial viability. It was suggested that the improvement
      of myocardial uptake after PTCA was due to incomplete fill-in in cases with AP
      and that the presence of fill-in was important for level of fill-in in patients
      with AP. The improvement of myocardial uptake in the scar tissue in patients with
      OMI contributed to the hibernating myocardium. We concluded that correct
      detection of hibernating myocardium was difficult despite the superior imaging
      capability of 99mTc-tetrofosmin myocardial SPECT.

PMID- 9267123
TI  - [Simplified analytical method of 99mTc-labeled phosphonate].
AB  - A simplified and rapid analytical method of 99mTc-labeled phosphonates was tested
      using a mini-column based on an anion-exchange type of cartridge. Free 99mTcO4-
      in the prepared solutions of 99mTc-labeled phosphonate was eluted from the column
      by a neutral phosphate buffer solution. Partly components of the 99mTc-labeled
      phosphonates was eluted from the column by a 100 mM sodium phosphonate solution,
      while the residual components were not eluted from the mini-column. In addition,
      for analysis of 99mTc-labeling rate in 99mTc-MDP solution, this method requires
      much less time than thin layer chromatography (TLC). Therefore, the method is
      more suitable for analysis of 99mTc-labeled phosphonates than TLC now in use,
      particularly rapid analysis for 99mTc-labeling rate of the compounds and the
      stability.

PMID- 9267125
TI  - [Quantitative evaluation of response at acetazolamide test using 99mTc-ECD SPECT;
      a trial of production of the response map].
AB  - In the method by Matsuda and Takeuchi et al. for easy regional cerebral blood
      flow (rCBF) measurements at pre- and post-acetazolamide tests using 99mTc-ECD, a
      study was done for producing the increase rate of rCBF as a response map after
      acetazolamide administration. To prepare the response map calculated from the
      arithmetic operation of [(rCBF image at administration--rCBF image at rest)/rCBF
      image at rest x 100], the images were preprocessed by combination of matrix size
      conversion and smoothing techniques and then areas outside the brain were masked
      to remove amplified noises. The response map seemed helpful for visual evaluation
      of the response after acetazolamide administration, and also for understanding
      the disease conditions and clinical courses.

PMID- 9267127
TI  - [A preliminary study on transurethral electrovaporization of the prostate (TVP)
      using VaporTrode].
AB  - BACKGROUND: Surgical therapy for Benign Prostatic Hypertrophy (B.P.H.) has mainly
      depended upon Transurethral Resection of the Prostate (TUR-P) using a cutting
      loop electrode. Recently, a new technique TVP was reported using the VaporTrode
      apparatus. We assessed the safety and efficacy of the VaporTrode in a preliminary
      study. METHODS: Histological changes of the muscle and liver of pigs were
      examined after vaporization using the VaporTrode and a cutting loop electrode.
      First, histological changes were investigated following vaporization after one
      stroke at a slow hand speed. Next, histological changes were assessed following
      vaporization at fixed stroke speed in an experimental model. RESULTS: At an
      electrical output of less than 275 W, the depth of the vaporized layer increased
      as the stroke speed became slower (4.0 cm/s-2.5 cm/s). When the electrical output
      was 300 W, the depth of vaporized layer increased even at a faster stroke speed
      (2.5 cm/s-3.0 cm/s.) The depth of the desiccated layer increased as the stroke
      speed became slower at any electrical output. However, when the stroke speed was
      4.0 cm/s, the depth of this layer was less than 2.0 mm. With the cutting loop
      electrode, the depth of the desiccated layer increased at a higher electrical
      power, but the change was very small. CONCLUSION: To achieve deep enough
      vaporized and desiccated layers safely, the VaporTrode should be used at a stroke
      speed slower than 3.0 cm/s and a high electrical power of about 275 W.

PMID- 9267126
TI  - [Evaluation of clinical utility of 111In-DTPA-IgG scintigraphy in the detection
      of inflammation/infection--a report of multicenter phase III clinical trials].
AB  - This is the report of phase III study to evaluate the safety and utility of 111In
      DTPA-IgG in patients with strongly suspected inflammation/infection. One hundred
      and forty five patients with suspected sites of inflammation/infection were
      enrolled in the study. Only a few adverse experiences in one patient were
      reported, which were interpreted as having a possible relationship to the agent.
      A total of 171 suspected sites (12 in head and neck, 39 in thorax, 44 in abdomen
      and pelvis, 62 in musculoskeletal system, and 14 in other regions) were evaluated
      by investigators at each institute. Out of 171 sites, 18 were determined to be
      unevaluable, and 12 false negative and 5 false positive cases were observed.
      Overall sensitivity and specificity was 89.8% and 85.7%, respectively, and the
      agent proved to be effective in detecting lesions anywhere throughout the body.
      The analysis of data from this Phase III study indicates that 111In-DTPA-IgG is
      well-tolerated in patients and effective in determining focal sites of
      inflammation/infection although the physiological accumulation in some tissues
      such as the sinus or liver and possible excretion into the gastrointestinal tract
      may make it difficult to localize lesions.

PMID- 9267128
TI  - [A study on testicular aromatase activity--spermatogenic damage in high
      testicular E2 models of rat].
AB  - BACKGROUND: In order to study the influence of testicular estrogen concentration
      on spermatogenesis, we conducted the following experiments. METHODS: Eight-week
      old male Sprague-Dawley rats were used and two kinds of experiments were
      prepared. In experiment one (intraperitoneal injection), five groups were set up:
      control (saline solution), estradiol (E2), human chorionic gonadotropin (hCG),
      aromatase inhibitor (A.I.) and hCG+A.I. group. In experiment two (intratesticular
      injection), two groups were set up: control (saline solution) and E2 microcrystal
      suspension (Emcs) group. The experimental period was 28 days. At sacrifice, we
      evaluated the concentrations of serum testosterone (T) and E2, testicular T and
      E2, testicular aromatase activity and the seminiferous tubular diameter. RESULTS:
      Exp. 1: In the hCG group, the rate of testicular aromatase activity and
      testicular E2 level were higher and the diameter of seminiferous tubules was
      smaller than in the control group. However, these changes were not observed in
      the hCG+A.I. group. Exp. 2: In the Emcs group, testicular E2 level showed an
      increase without elevation of serum E2 level, and the diameter of seminiferous
      tubules was atrophic. CONCLUSION: It was suggested that the increase of the rate
      of testicular aromatase activity and the following elevation of testicular E2
      level is possibly one of the causes of male infertility.

PMID- 9267129
TI  - [Changes in tissue and blood polyamines during N-butyl-N-(4-hydroxybutyl)
      nitrosamine-induced bladder carcinogenesis in rats].
AB  - BACKGROUND: Polyamine are recognized as cell growth factors. We studied in order
      to determine whether alterations in the levels of tissue and blood polyamines
      were useful biochemical markers for bladder tumor. METHODS: The concentrations of
      three polyamines, diamine, spermidine and spermine, in urinary bladder and blood
      were determined during N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced
      bladder carcinogenesis in male F344 rats. At 5 weeks of age, rats were given
      0.05% BBN in the drinking water for 20 weeks. RESULTS: BBN induced bladder
      hyperplasia in 4 of 5 rats at 8 weeks, papillomas in 2 of 5 rats at 12 weeks, and
      transitional cell carcinoma in all the rats by 20 weeks. The levels of total
      polyamine in both bladder and blood of the rats during 12-20 weeks were
      significantly higher than those of the control animals given water alone. The
      elevation of total polyamine was mainly due to the increase of spermidine of the
      three polyamines, which was coincident with the incidence of bladder tumors.
      CONCLUSION: The results indicated that the polyamines are excellent biochemical
      markers for bladder tumors.

PMID- 9267130
TI  - [Pathological study of the kidney and the lung in patients with Potter sequence].
AB  - PURPOSES: The condition in infants showing the characteristic facial
      abnormalities, limb deformities, and pulmonary hypoplasia induced by
      oligohydramnios is termed Potter sequence (PS). In addition to bilateral renal
      agenesis, Potter sequence could be caused by other urological abnormalities such
      as cystic dysplasia and obstructive uropathy. Although lethal in most of the
      patients with PS, some exceptional infants were reported to survive in spite of
      the antenatal demonstration of oligohydramnios from renal abnormalities. These
      surviving patients put new questions to us regarding the management of both
      respiratory and renal failure starting from the newborn periods. The diversity of
      clinical courses in patients with antenatally detected PS may imply that this
      entity has a spectrum of severity. Our study of infants autopsied on the
      diagnosis of PS was undertaken to determine various histological grade of the
      kidneys and the lungs. MATERIALS AND METHODS: Thirty-two autopsy cases of PS (19
      males and 13 females) diagnosed by the presence of the characteristic stigmata,
      oligohydramnios, and renal or urological abnormalities were studied
      retrospectively. Patients were divided according to the urological abnormalities
      into 3 groups; renal hypodysplasia, urinary obstruction, and polycystic kidney
      disease (PCKD). Renal histology was evaluated by two parameters; renal glomerular
      count (RGC), and dysplastic grade. Developmental aspects of the lung were judged
      by lung/body-weight ratio (L/ B ratio) and radial alveolar count (RAC) proposed
      by Emery. RESULTS: The underlying urological disorders included renal
      hypodysplasia in 22 patients, obstruction in 7, and polycystic kidney disease in
      3. Dysplastic grade of 29 patients with hypodysplasia and obstruction consisted
      of grade 4 in 12 patient, grade 3 in 9, and grade 2 in 8. In 10 kidneys from 8
      patients with grade 2-dysplasia, RGC was significantly fewer than that of normal
      fetuses for the gestational age. The term patient with PS showed the glomerular
      count equivalent to normal fetus of around 25 weeks of gestation. L/B ratio
      indicated definite pulmonary hypoplasia in 25 of 29 patients. The ratio was much
      smaller than normal in another 4 patients. RAC was calculated in 24 patients; of
      these only 2 had normal count for gestational age. In another 22, the number of
      air space stopped to increase at about 20 to 25 weeks of gestation. There was a
      tendency for L/B ratio to decrease according to dysplastic grade (1.3% for grade
      2 vs. 0.9% for grade 3 and 4). CONCLUSION: The primary urological abnormalities
      leading to PS included bilateral renal hypodysplasia, obstructive uropathy, and
      PCKD. Histological study of the kidneys indicates that PS is the spectrum disease
      with various degree of nephron formation. The development of the lung depends, in
      part, on the grade of renal dysplasia.

PMID- 9267131
TI  - [Transurethral microwave thermotherapy for benign prostatic hyperplasia].
AB  - BACKGROUND: We studied the clinical efficacy of transurethral microwave
      thermotherapy (TUMT) using Endotherm UMW system (OLYMPUS). METHODS: TUMT was
      performed in 28 patients with benign prostatic hyperplasia (BPH). Three patients
      of them were catheterized because of urinary retention. The treatment was
      performed in a single session for an hour. The urethral surface temperature was
      set at 39 degrees C, and the coolant flow of the urethral applicator (21 Fr
      balloon catheter) was set at 30 ml/min, to heat up the broad area of the prostate
      up to 45 degrees C. The clinical efficacy was evaluated by analyzing subjective
      responses, using the International Prostate Symptom Score (I-PSS) scale (S) and
      QOL score (L), and objective responses, using peak urinary flow rate (Qmax),
      average flow rate (Qave), residual urine volume and prostate volume following the
      treatment. RESULTS: At 24 weeks after the treatment, significant improvement were
      observed in S score (41%), L score (37%), Qmax (53%) and Qave (62%). Although
      there was no significant decrease in residual urine and prostate volume. The
      three patients, with a catheter indwelled because of urinary retention, were all
      free of the catheter within 4 weeks after the treatment. During and after the
      treatment, no severe adverse effects, including transient urinary retention
      needed for indwelling a catheter, was detected. CONCLUSION: A single session of
      TUMT by Endotherm UMW considered to be safe and useful for symptomatic BPH
      patients, even who are not indicated for transurethral resection of the prostate
      (TUR-P) because of underlying disorders.

PMID- 9267132
TI  - [Prostatic involvement of bladder carcinoma].
AB  - BACKGROUND: The histological pattern of prostatic involvement by transitional
      cell carcinoma is still unclear. The present study was carried out in bladder
      carcinoma with prostatic involvement to clarify the histological invasion pattern
      and its association with primary lesions. METHODS: In the past 10 years, 83 cases
      of total cystectomy including prostatectomy underwent pathological diagnosis in
      our department. This study included 81 cases of transitional cell carcinoma
      (TCC), of which 11 showed prostatic involvement of bladder carcinoma. In these
      cases, the histological patterns of invasion were classified in relation to
      prostatic urethra, prostatic duct, stroma, lymphatic duct, capsule, vein and
      perineural invasion. Seventy cases without prostatic involvement were controls.
      The location, pathological grade, stage and lymphatic involvement of primary
      bladder carcinoma were compared in terms of prostatic involvement cases with
      control cases. RESULTS: Among those 11 cases, there were 3 cases in which only
      the prostatic duct was involved, 2 cases with invasion to only lymphatic duct,
      and involvement of both in 6 cases. One case of the prostatic duct involvement
      showed non-continuous invasion in the prostatic duct without prostatic urethra
      invasion, suggesting the possibility that non-continuous invasion could occur as
      a type of multicentric growth of TCC. CONCLUSIONS: Suspected routes of invasion
      of bladder carcinoma into the prostate were; 1 continuous transductal, 2 trans
      lymphatic ductal, 3a combination of the two. It appears necessary to consider the
      possibility of TCC occurring in the prostate simultaneously with bladder
      carcinoma as a part of multicentric growth. There was a tendency of prostatic
      involvement cases include the bladder neck and trigone, and show lymphatic duct
      involvement more than non-prostatic involvement cases.

PMID- 9267133
TI  - [Measurement of relative plasma volume and plasma refilling rate during
      ultrafiltration of hemodialysis by measuring apparatus of plasma colloidal
      osmotic pressure].
AB  - BACKGROUND: The objective of this study is the prevention of unexpected
      hypotension during hemodialysis caused by unsuitable filtration rate. METHODS:
      The plasma colloidal osmotic pressure (COP) was measured continuously during
      ultra-filtration, and relative plasma volume (%PV) and plasma refilling rate
      (PRR) were calculated during 12 ECUMs and one dialysis on twelve patients in
      early stage of chronic renal failure. Values of %PV and PRR calculated from COP
      were drawn in graphic curves, and analysed to obtain characteristic pattern.
      Minimum value of %PV (%PV min), maximum value of PRR (PRRmax) and time for PRR to
      decrease to 95% (95% PVt) on the curves were documented simultaneously. RESULTS:
      At the initial stage of %PV curve, obvious fall was observed on 6 of 13
      estimation (initial fall of %PV). On the contrary at the initial stage of PRR
      curve, obvious rise was observed on 5 estimation (initial rise of PRR). A close
      relationship was indicated between the two phenomenons. In 6 cases with initial
      fall of %PV and in 5 cases with initial rise of PRR body weight, PRRmax and
      95%PVt were lower than another cases without it. The ultra-infiltration velocity
      was estimated to be relatively high in these groups. In these 8 cases, filtrated
      water volume was judged as adequate clinically. In 4 of 5 cases without final
      fall of PRR, it was judged as inadequate and needed to evacuate more 0.9 to 3.0
      kg (average of 1.8 +/- 1.07) of water from the patients. CONCLUSIONS: From the
      above, we concluded that our method is useful for deciding suitable velocity of
      ultrafiltration and dry weight in hemodialysis therapy.)

PMID- 9267134
TI  - [A case of fulminant hepatitis caused by antiandrogen, flutamide in a patient
      with prostate cancer].
AB  - Luteinizing hormone-releasing hormone analogue, 3.6 mg goserelin acetate and
      flutamide, 375 mg per day were used to treat metastatic prostate cancer in a 66
      year-old male. Marked increase in serum aminotransferases and total bilirubin
      levels was noted after 7 weeks of treatment. The enzyme levels returned to normal
      at 2 months following discontinuation of the treatment. Though incidences of
      severe hepatotoxicity are rare (0.003-0.18%), cases of flutamide-induced death
      have been reported. Careful monitoring of patients is mandatory while
      administering flutamide.

PMID- 9267135
TI  - [Enhancement pattern of hepatic metastases from colorectal cancer on CT
      arteriography].
AB  - The enhancement pattern of hepatic metastases from colorectal cancer on CT
      arteriography (CTA) was evaluated in 79 cases with 405 lesions. Sixty-two percent
      of overall lesions irrespective of size showed ring-like enhancement, and 33% of
      lesions less than 1 cm in diameter showed homogeneous enhancement. In
      pathological examination of 59 resected lesions, the enhancement pattern on CTA
      had a good correlation with the extent of tumor cellularity, necrosis or fibrosis
      in the lesions. And in 8.5% of resected lesions, the extent of enhancement on CTA
      was larger than that of perfusion defect on CT arterial portography, which was
      almost equal to the size in the resected specimen. In such lesions, the
      enhancement on CTA might include enhancement of normal hepatic parenchyma around
      the lesion.

PMID- 9267137
TI  - [CT analysis of the anterior mediastinal fat: before and after lobectomy].
AB  - CT analysis was performed to evaluate change in the anterior mediastinal fat
      (AMF) after lobectomy and differences in AMF in the lobectomized region. In 67
      carcinoma patients who underwent lobectomy, the area and volume of AMF were
      measured on CT before and after surgery. Mediastinal deviation after lobectomy
      was also correlated to the altered fat tissue. The postoperative AMF distribution
      was distinctly changed in the left upper lobectomy (LUL) group, showing a marked
      increase from the infra-aortic arch to the carina level, with converse decreases
      in upper and lower slices. No significant post-operative change was noted in
      total AMF volume. There was a close correlation between changes in AMF area and
      mediastinal deviation after lobectomy, and postoperative mediastinal deviation
      was also greater the in the LUL group than in any other group. In conclusion,
      postoperative change in the AMF area was distinctly different in the LUL group.
      Redistribution of displaced AMF is considered to be the main cause of seemingly
      increased fat tissue.

PMID- 9267136
TI  - [Accuracy and clinical utility of quantitative proton magnetic resonance
      spectroscopy (MRS) on phantom and chronic cerebral ischemia].
AB  - We quantified the concentration of metabolites observed by proton MRS using the
      tissue water signal as an internal standard. A phantom containing known
      concentrations of NAA (10 mM) and Cr (5 mM) was used for the study of
      methodological accuracy. Clinical utility was evaluated by the measurement of
      patients with severe stenosis or obstruction of the unilateral internal carotid
      artery. The concentration of tissue water was compensated using a proton-density
      weighted image measured with a water bag attached to the head. The calculated
      concentrations of NAA and Cr in the phantom were 9.2 mM (SD: 1.2) and 5.6 mM (SD:
      0.7), respectively. On the ischemic side of the brain, the concentrations of NAA
      and Cr were lower than on the opposite side, but the concentration of choline
      (Cho) was almost the same on the two sides. The NAA/Cr ratio showed no
      statistically significant differences between the two sides, because the
      concentration of Cr was shown to be decreased in the ischemic area. We consider
      that quantitative evaluation of proton MRS might reveal changes in single
      metabolites clearly, thereby facilitating understanding of the results of proton
      MRS.

PMID- 9267138
TI  - [MR imaging appearances of schwannoma: correlation with pathological findings].
AB  - Peripheral schwannomas are nerve sheath neoplasms that consist of focal
      proliferation of Schwann cells. We reviewed the MRI findings in 17 patients with
      pathologically proved peripheral schwannomas. When compared with the signal
      intensity of muscle, that of the mass was isointense or hyperintense on T1
      weighted images and hyperintense in all 17 tumors on T2-weighted images. All of
      the masses showed heterogeneous enhancement following the intravenous injection
      of Gd-DTPA on T1-weighted images. On T1-weighted images, hyperintensity was
      observed in the tumors that contained predominantly hypercellular Antoni type A
      tissue, while isointensity was observed in the tumors that contained
      predominantly hypocellular Antoni type B tissue. Relatively high signal intensity
      seen on T2-weighted images and Gd-DTPA enhanced T1-weighted images was observed
      in the tumors that contained predominantly Antoni type B tissue when compared
      with the signal intensity of tumors that contained predominantly Antoni type A
      tissue. A capsule was pathologically identified in 15 of 17 tumors. MRI correctly
      identified the presence of a capsule in 11 of 15 tumors and the absence of a
      capsule in one of 2 tumors. Thus the diagnostic accuracy was 71% (12/17). The
      cause of 4 false negative results appeared to be a hemorrhage or cystic change
      around the peripheral portion of the tumor, and it appeared to be a chemical
      artifact in one false positive result. Thus the appearance of MRI may suggest the
      cellular type of schwannoma, Antoni type A or B. However, prediction of the
      presence or absence of tumor capsule may be relatively difficult with MRI.

PMID- 9267139
TI  - [Radiation therapy for uterine cervix cancer: importance of evaluation of pre
      treatment tumor size with MR imaging].
AB  - From May 1992 through December 1995, a total of 42 patients with previously
      untreated squamous cell carcinoma of the uterine cervix were treated by using
      middle-dose-rate intracavitary therapy, and their previously treated local tumor
      volume was evaluated with MRI. According to the staging of FIGO, 2 patients were
      classified as Stage IB, 2 as IIA, 18 as IIB, 1 as IIIA, 14 as IIIB, 2 as IVA and
      3 as IVB. Cumulative 3-year survival rates were 89% in Stage IIB and 54% in IIIB.
      3-year local control rates were 100% in Stage IIB and 67% in IIIB. On the other
      hand, the cumulative survival rate for the local control group in all stages was
      100% at 2 years and 82% at 3 years. For the pelvic failure group it was 41% at 2
      years. All of those in the pelvic failure group had bulky local tumor sizes of
      more than 60 mm in the previous treatment MRI study. The 3-year cumulative
      survival rate and local control rate for tumors less than 60 mm were 84% and
      100%, but for tumors over 60 mm the respective rates were 45% and 33% (p < 0.01).
      The a results showed that the group with pretreatment of local tumors over 60 mm
      on MRI had a poor outcome. We concluded that pretreatment tumor volume is an
      important factor in prognosis and the evaluation of pretreatment tumor volume by
      imaging study (MRI) is necessary.

PMID- 9267140
TI  - [Effect of daily administration of oral etoposide for non-small cell lung cancer
      treated with concurrent radiation therapy].
AB  - The purpose of this study was to explore the effect of daily administration of
      oral etoposide (25 mg) for patients with non-small cell lung cancer treated with
      concurrent radiation therapy. Planned endpoints were response, survival and
      toxicity. Forty-one patients with non-small cell lung cancer were divided into 25
      patients given daily oral etoposide (25 mg) with concurrent radiation therapy
      (ERT group) and 16 patients given radiation therapy alone (RT group). Etoposide
      was administrated in the morning throughout radiation therapy. The median total
      irradiated dose was 63.1 Gy in the ERT group and 64.0 Gy in the RT group. Twenty
      four patients completed therapy in the ERT group and 16 in the RT group. Three
      (15%) ERT patients achieved complete response (CR) and 9 (45%) achieved partial
      response (PR). In the RT group, no patients achieved CR and 9 (69%) achieved PR.
      One-year survival was 22.6% with ERT and 23.0% with RT. The prognosis of stage
      III patients in the ERT group was worse than that in the RT group because
      radiation pneumonitis and radiation esophagitis were more severe with ERT. In
      conclusion, the ERT group had better local response but worse in survival than
      the RT group. Complications of ERT were severe enough to cause death in some
      patients. ERT had no clear advantage over RT.

PMID- 9267141
TI  - [Evaluation of neuro-Behcet disease with 99mTc-HMPAO brain SPECT: comparison with
      MR imaging].
AB  - The purpose of this study was to evaluate the brain perfusion of neuro-Behcet
      disease using 99mTc-HMPAO. In total, nine patients (7 men and 2 women) were
      evaluated. Seven were in the chronic phase, one was acute and the other was
      subacute. The results of perfusion study were compared with the MRI findings. The
      findings of chronic-phase neuro-Behcet disease were as follows: 99mTc-HMPAO
      showed hypoperfusion of the cerebellum in 3, brain stem in 5, and cerebral cortex
      in 4 patients. Moreover, asymmetry of the basal ganglia and thalamus was seen in
      4 cases with 99mTc-HMPAO. MRI showed atrophy of the cerebellum in 4, brain stem
      in 5 and cerebral cortex in 2 patients. One acute patient showed a perfusion
      defect with 99mTc-HMPAO that was consistent with the vasculitis shown with MRI.
      In the remaining subacute patient, perfusion defect was demonstrated with 99mTc
      HMPAO, consistent with the infarction shown with MRI. It is concluded that brain
      perfusion scintigraphy is useful to evaluate the brain blood flow of neuro-Behcet
      disease.

PMID- 9267142
TI  - [Preoperative evaluation for volume reduction surgery of pulmonary emphysema
      using MRI: usefulness of HASTE (half-Fourier single-shot turbo SE) sequence
      during deep respiration].
AB  - Volume reduction surgery has recently been an important surgical procedure for
      patients with severe pulmonary emphysema. We compared the sagittal and coronal
      images taken by the HASTE sequence with those obtained by turbo FLASH during deep
      breathing and with CT images obtained under deep inspiration. Clear images were
      obtained from both sequences, without cardiac or respiratory motion artifacts.
      The emphysematous areas were demonstrated as low signal intensity areas, as in CT
      images. The ratio of signal intensity in the expiratory phase to that in the
      inspiratory phase was lower than that of volunteers in the HASTE sequence. The
      HASTE sequence provides useful information about respiratory movement as well as
      about changes in the pulmonary parenchyma when used for preoperative examination.

PMID- 9267144
TI  - Esophageal intramural pseudodiverticulosis with esophageal cancer improved by
      target rotation irradiation: case report.
AB  - Etiology of esophageal intramural pseudodiverticulosis is still unknown but
      several accompanying diseases have been reported, for example, reflux
      esophagitis, esophageal cancer, diabetes mellitus and so on. We have experienced
      a case of esophageal intramural pseudodiverticulosis with cancer improved by
      radiation therapy. In this case, there were esophageal cancer in the cervical
      esophagus, with intramural spreading in whole esophagus. This case was delivered
      irradiation to the entire esophagus by target rotation method. After irradiation,
      intramural pseudodiverticula, intramural spreading and primary site of esophageal
      cancer were improved. This is an interest case report that esophageal intramural
      pseudodiverticula with cancer was disappeared by radiation therapy.

PMID- 9267143
TI  - [Experiment in ultra-rapid injection of isotonic sodium chloride after injection
      of contrast medium: time-density analysis of the aorta and portal vein].
AB  - Ultra rapid injection of isotonic sodium chloride after the injection of contrast
      medium may make it possible to clearly distinguish between the arterial phase and
      the portal phase. This method could improve the detectability of hepatocellular
      carcinoma on double phase dynamic spiral CT. A time-density analysis of the aorta
      and the portal vein was carried out according to the following 2 protocols (5
      cases each). In protocol 1, 95 ml of Iopamidol (300 mgI/ml) was injected at a
      rate of 3 ml/second, while the protocol 2, 40 ml of isotonic sodium chloride was
      injected at a rate of 10 ml/second after the injection of 60 ml of Iopamidol (300
      mgI/ ml) at a rate of 10 ml/second. The duration of the arterial phase (aortic
      enhancement unit (EU) > or = 200) in protocol 2 was 11 seconds, which was shorter
      than that in protocol 1. In protocol 2, the duration of the clearly portal
      dominant phase (reversal phase; aortic EU < portal EU) was about 11 seconds.

PMID- 9267145
TI  - [Insulin resistance and cardiovascular disease incidence in a elderly Japanese
      population: the Hisayama study].

PMID- 9267146
TI  - [Glucose tolerance and insulin resistance in the elderly].
AB  - Glucose tolerance is reported to be impaired in the elderly, and this is said to
      be mainly due to a decrease in insulin sensitivity (insulin resistance). Insulin
      resistance is known to be associated with atherosclerosis and coronary artery
      disease. To clarify whether or not age-dependent changes in glucose tolerance and
      insulin sensitivity are risk factors for coronary artery disease, as they are in
      the case of the insulin resistance syndrome, we studied age-dependent changes in
      glucose tolerance, insulin sensitivity, blood pressure, and serum lipids in a
      large number of subjects who underwent annual health check-ups, and then studied
      the relationships between coronary artery disease and aging, insulin sensitivity,
      and other risk factors in subjects who underwent coronary angiography. Aging was
      associated with an increased prevalence of noninsulin-dependent diabetes mellitus
      and impaired glucose tolerance; even in subjects with normal glucose tolerance,
      plasma glucose levels during an oral glucose tolerance test were significantly
      higher in the elderly. Insulin sensitivity, as assessed by the ratio of the sum
      of the plasma glucose divided by the sum of the serum insulin during the test
      (sigma PG/sigma IRI), was significantly lower in subjects over 60 years old than
      in younger subjects. Age-dependent impairment of insulin sensitivity and glucose
      tolerance was associated with increased blood pressure and serum cholesterol
      levels, but not with changes in boy mass index or serum triglyceride levels. As
      an independent variable, aging, but not insulin sensitivity, was related to the
      severity of coronary artery disease. These data suggest that aging is associated
      with glucose intolerance, insulin resistance, and an increased risk of coronary
      artery disease, but that the effect of aging on coronary artery disease cannot be
      explained by insulin resistance alone. Other factors, such as glucose intolerance
      and increased blood pressure, in addition to insulin resistance, appear to be
      responsible of the increased risk for coronary artery disease in the elderly.

PMID- 9267148
TI  - [Obesity and insulin resistance in the elderly].

PMID- 9267147
TI  - [Insulin resistance in elderly patients with hypertension].
AB  - Insulin resistance and hyperinsulinemia have been linked to essential
      hypertension. Some epidemiological studies showed that the prevalence of
      hypertension, glucose intolerance, and diabetes mellitus increase with advancing
      age. Among normotensive subjects, insulin sensitivity was significantly lower in
      the elderly than in the young. A significant negative correlation was found
      between insulin sensitivity and age. During hyperinsulinemia, urinary sodium
      excretion and fractional excretion of sodium did not change in young normotensive
      subjects, but they decreased significantly in elderly normotensive subjects.
      Increases in plasma norepinephrine concentration and in plasma activity were
      observed in normotensive subjects of all ages. Among patients with essential
      hypertension insulin sensitivity did not differ between age groups. No age
      related decrease in insulin sensitivity (as found in normotensives) was observed,
      and insulin sensitivity in patients with essential hypertension was low, even in
      those who were young. In both young and elderly hypertensive subjects, urinary
      sodium excretion and fractional excretion of sodium decreased, and plasma
      norepinephrine concentration and plasma renin activity increased significantly
      during hyperinsulinemia. These results indicate that 1) reduction in insulin
      sensitivity plays a role in age-related acceleration of hypertension and of
      glucose intolerance; 2) in patients with essential hypertension, selective
      insulin resistance with respect to glucose metabolism can be found even in those
      who are young; and 3) both sodium retention and pressor system activation via
      insulin might cause blood pressure to increase in patients with essential
      hypertension.

PMID- 9267149
TI  - [Insulin resistance and hyperlipidemia in the elderly].
AB  - To elucidate the relationship between hyperlipidemias and insulin resistance in
      the elderly, we conducted three studies: 1) determination of the prevalence of
      hyperlipidemias in elderly subjects with impaired glucose tolerance or non
      insulin dependent diabetes mellitus, 2) measurement of plasma glucose and insulin
      levels in patients with phyerlipidemias and atherosclerotic vascular disease, and
      3) computation of correlation between levels of substances involved in
      coagulation and fibrinolysis (F-VII, F-X, and PAI-1) and levels of triglycerides
      and insulin in serum in hyperlipidemic patients with atherosclerotic vascular
      disease. The prevalence of hypertriglyceridemia was 4% in non-diabetic control
      subjects, 38% in subjects with impaired glucose tolerance, 22% in those with
      diabetes, and 29% in those with both conditions. Levels of glucose and insulin in
      plasma were measured after oral intake of 75 g of glucose. The insulin response
      was greater in the group with hypertriglyceridemia than in the group with normal
      triglyceride levels, although the glucose responses did not differ between the
      groups. The activities and levels of F-VII, F-X, and PAI-1 correlated with
      triglycerides in serum and also with fasting insulin levels in hyperlipidemic
      patients with atherosclerotic vascular disease. We conclude that
      hypertriglyceridemia plays an important role in the development of
      atherothrombotic vascular disease; it accompanies elevation of coagulation and
      antifibrinolytic activities in elderly patients with insulin resistance.

PMID- 9267150
TI  - [Effects of atherogenic risk factors on asymptomatic brain infarct].
AB  - This study was done to clarify the relationship between asymptomatic brain
      infarcts and risk factors for atherogenis. A total of 312 patients (151 men and
      161 women) who had no neurologic deficits were enrolled. Their ages ranged from
      41 to 83 years (mean age 63 years). The patients were divided into two groups:
      158 patients without asymptomatic brain infarct and 154 patients with at least
      one asymptomatic brain infarct of at least 5 mm as diagnosed by magnetic
      resonance imaging. The patients with asymptomatic brain infarct were more likely
      than those without asymptomatic brain infarct to be 65 years old or older, and to
      have essential hypertension, diabetes mellitus, or atrial fibrillation. Among
      patients with hypertension the frequency of left ventricular hypertrophy or
      hypertensive ocular findings (Scheie's class H2) was significantly higher in
      those with asymptomatic brain infarct than in those without asymptomatic brain
      infarct. These results indicate that aging, essential hypertension (especially
      with left ventricular hypertrophy or hypertensive ocular findings), diabetes
      mellitus, and atrial fibrillation are associated with asymptomatic brain infarct.

PMID- 9267151
TI  - [Improvements in mental and physical status of elderly patients with dementia
      after institutionalization--assessment with a minimum data set].
AB  - Using a Minimum Data Set, we studied how the mental and physical status of
      elderly people with dementia was modified by institutionalization. We assessed
      patients with dementia at the time of their admission in Kyoto Higashiyama
      geriatric hospital, and again three months later. On admission, both mental and
      physical problems were noted with a Resident Assessment Protocols. The former
      included cognitive loss/dementia, delirium, behavioral problem, activities, and
      mood state; the latter included visual function, activities of daily living
      (functional), urinary incontinence and indwelling catheter, nutritional status,
      dehydration/fluid maintenance, and dental care. Three months later, marked
      improvements were observed in 8 areas: delirium, psychological well-being, mood
      state, activities, urinary incontinence and indwelling catheter, nutritional
      status, dehydration/fluid maintenance and dental care. Cognitive loss/dementia
      and visual function were changed little. The unchanged areas were considered to
      be "core" manifestations of dementia, and those that changed were believed to
      reflect emotional problems and to be affected by the environment. Therefore,
      individualized care for elderly institutionalized patients with dementia should
      focus on these "peripheral" problems rather than on those that cannot be changed.

PMID- 9267152
TI  - [Mechanism of silent myocardial ischemia in elderly patients with coronary artery
      disease--assessment by dipyridamole thallium scintigraphy].
AB  - To evaluate the clinical significance of silent myocardial ischemia in elderly
      patients with coronary artery disease, 147 patients (aged 65 years and older)
      underwent coronary angiography and dipyridamole thallium scintigraphy. Seventy
      four patients (44 men, 30 women) who showed reversible defects (RD) and ischemic
      ST depression during scintigraphy were divided into two groups: 13 with silent RD
      (18%, 12 men, 1 woman), and 61 with painful RD (82%, 32 men, 29 women). Most
      patients with silent RD were men. The prevalence of myocardial infarction was
      similar in patients with silent RD (62%) and in patients with painful RD (49%).
      The prevalence of multivessel disease was also similar in the two groups: 85% in
      patients with silent RD and 82% in patients with painful RD. Among 38 patients
      with infarction, 8 had silent RD and 30 had painful RD. The prevalence of RD in
      the area of infarction was greater in patients with silent RD (63%) than in
      patients with painful RD (47%), but the difference was not statistically
      significant. The prevalence of extensive infarction (fixed defects) was greater
      in patients with silent RD (75%) than in patients with painful RD (30%, p <
      0.05). Among 36 patients without infarction, there was no scintigraphic parameter
      which showed significant difference. Bypass grafting and angioplasty were
      initially performed in 23% of the patients with silent RD and in 36% of the
      patients with painful RD (ns). When the two groups were treated medically during
      the follow-up period of 29 +/- 22 months, the incidences of cardiac events were
      similar: 10% in patients with silent RD and 13% in patients with painful RD. The
      prevalence of silent RD is not high in elderly patients with significant coronary
      artery disease. Compared with the patients with painful RD, those with silent RD
      were more likely to have an old and extensive myocardial infarction, and they
      tended to have RD in the area of the infarct.

PMID- 9267153
TI  - [Correction of urinary calcium levels for urine osmotic pressure].
AB  - The usefulness of the urinary calcium/creatinine (Ca/Cr) ratio, the oldest marker
      of bone resorption, is limited because of the influence of sodium intake and
      urine volume. The urinary Ca/Cr ratio was therefore compared with urinary calcium
      corrected for the urine osmotic pressure (Ca/OSM). Significant correlations are
      found between the Ca/Cr ratio and both creatinine (r = -0.386) and osmotic
      pressure (r = -0.473) in random urine samples from normal subjects, but similar
      correlations were not found for urine Ca/OSM. No significant correlation was
      found between Ca/OSM and Na/OSM, but the correlation coefficient between Ca/Cr
      ratio and Na/Cr ratio was 0.399. Thus, the Ca/Cr ratio is affected by urinary
      volume and sodium concentration, but the Ca/OSM ratio is not. The Ca/OSM ratio
      may therefore be a more accurate marker of bone resorption, because one of the
      main components of urinary osmotic pressure is sodium that inhibits tubular
      calcium reabsorption. The Ca/OSM ratios measured from 24-hour urine samples were
      found to be strongly correlated with the values measured from samples obtained
      during sleep (sleep urine, 0.823) and were slightly less strongly correlated with
      the values measured from second morning samples (0.641). Because bone resorption
      is especially active at night, the Ca/OSM ratio in sleep urine may be the most
      sensitive marker of bone resorption. The Ca/OSM ratio in sleep urine samples
      increased with age in normal women.

PMID- 9267154
TI  - [Sjogren's syndrome with presenting as aseptic meningoencephaloradiculopathy in
      an elderly woman].
AB  - A 76-year-old woman was found to have acute aseptic meningoencephalitis with
      meningial irritation, disturbance of consciousness, elevation of cell counts in
      cerebrospinal fluid, and swelling of a right temporal-lobe lesion on a CT scan of
      the head. Muscle weakness in the lower extremities and urinary dysfunction
      developed and progressed gradually. The protein content of cerebrospinal fluid
      was high, and the distal latencies of F waves were prolonged, which suggested
      that the inflammation extended to the nerve roots. Sjogren's syndrome was
      diagnosed on the basis of atrophy of the labial salivary glands; invasions of
      lymphocytes and plasma cells to the intercellular space; and elevation of the
      titers of serum antinuclear antibody, anti-SS-A antibody, and anti-SS-B antibody.
      The patient had no xerosis. Aseptic meningoencephalitis was the first
      manifestation of Sjogren's syndrome. In recent years, several cases in which
      Sjogren's syndrome was associated with aseptic meningitis have been reported.
      However, we know of no previous report of such a case in a patient of this age.
      Aseptic meningoencephalitis can be the first manifestation of Sjogren's syndrome.

PMID- 9267155
TI  - [Two cases of papillary adenocarcinoma of the thyroid gland associated with
      chylothorax].
AB  - Case 1. An 85-year-old woman had a papillary adenocarcinoma of the thyroid gland
      and a pleural effusion. The pleural effusion appeared to be a chylous exudate and
      it did not re-accumulate after thoracenthesis. Thoracic imaging indicated that
      the chylothorax was caused by direct invasion of the thoracic duct by the thyroid
      carcinoma. Case 2. A 53-year-old woman had a 20-year history of recurrent
      chylothorax. She died due to sepsis one year after the third admission for
      dyspnea and chylothorax. The autopsy findings included papillary adenocarcinoma
      of the thyroid gland with metastasis to the left supraclavicular lymph nodes. The
      thoracic duct was inflamed, fibrotic, and completely obstructed. Invasion by the
      carcinoma may have compressed and destroyed the thoracic duct, and caused
      chylothorax. Recurrent inflammatory granulation caused total obstruction of the
      thoracic duct. Reports of chylothorax associated with carcinoma of the thyroid
      gland are rare.

PMID- 9267156
TI  - [An elderly patient with beriberi].
AB  - An 82-year-old man was admitted to the hospital in the summer of 1995 due to
      dyspnea, peripheral edema, and a tingling sensation and muscle weakness in all
      extremities. Physical examination showed heart failure and polyneuropathy.
      Laboratory data showed a low concentration of vitamin B1 (10 ng/ml normal 23.8
      45.9 ng/ml) and a low level of erythrocyte transketolase activity (0.58 IU/gHb
      normal 0.75-1.30 IU/gHb). A chest X-ray film revealed cardiomegaly
      (cardiothoracic ratio 57.1%) and ultrasonic cardiography revealed increased
      motion of the left ventricle. A diagnosis of beriberi was made. The disease in
      this case may have been caused by hard work in the summer heat. The patient was
      treated with thiamine and his symptoms and signs resolved within a few weeks. A
      search of the literature revealed no previous report of beriberi in a patient of
      this age, but reports of beriberi in older patients in Japan are more common now
      than in previous years. Beriberi should be included in the differential diagnosis
      of polyneuropathy in elderly patients.

PMID- 9267157
TI  - [Prognostic implication of DNA contents on long-term outcome of childhood acute
      lymphoblastic leukemia].
AB  - Prognostic value of cellular DNA content was evaluated in 189 children with acute
      lymphoblastic leukemia. Treatment outcome of the three different DNA index (DI)
      groups (Group A, DI = 1.0 vs. Group B, DI 1.01-1.15 vs. Group C, DI > or = 1.16)
      was compared between the two treatment risk groups (standard-risk and high-risk
      groups) stratified by the initial leukocyte count and age. In the standard-risk
      group, these groups had 10-year event free survival (EFS) rate (SE) of 62% (6%),
      40% (21%) and 87% (6%), respectively (p < 0.05). In the high risk group, they had
      10-year EFS rate of 30% (5%), 33% (27%) and 60% (19%), respectively (p < 0.01).
      Use of the DI, leukocyte count and age may be sufficient to distinguish the
      patients with an extremely low risk of failing to the standard ALL therapy from
      the patients with a relatively high-risk of treatment failure.

PMID- 9267159
TI  - [Diffuse alveolar hemorrhage associated with idiopathic interstitial pneumonia
      syndrome after allogeneic bone marrow transplantation].
AB  - A 24-year-old male with myelodysplastic syndrome (refractory anemia) was treated
      with allogeneic bone marrow transplantation (BMT) from HLA-identical brother on
      September 9, 1994, after conditioning with busulfan and cyclophosphamide. From
      early in April 1995, the patient complained of cough and fever. Chest X-ray
      showed interstitial infiltrates involving hilar and lower lung fields. Although
      pulmonary infiltrates were resolved with methylprednisolone pulse therapy, on May
      19, the patient rapidly deteriorated with dyspnea. Diffuse alveolar infiltrates
      appeared on chest X-ray and he died of respiratory failure. At autopsy, diffuse
      alveolar hemorrhage accompanied with thickening of the alveolar walls and
      interstitial infiltration of lymphocytes was demonstrated. There was no evidence
      of bleeding in other organs. This is a rare case of diffuse alveolar hemorrhage
      in the late stage of allogeneic BMT. This report should lead to an evaluation of
      this disease by the collection of similar cases.

PMID- 9267158
TI  - [Combined deficiency in neutrophil functions after bone marrow transplantation
      and the in vitro effect of granulocyte colony-stimulating factor].
AB  - In order to investigate the mechanism of susceptibility to bacterial infection
      after bone marrow transplantation (BMT), we evaluated the neutrophil functions at
      1, 3, 6, and 12 months after hematological reconstitution in a 29-year-old AML
      patient who received allogeneic bone marrow transplantation. Acute graft-versus
      host disease (GVHD) was grade I, and chronic GVHD was not present. The patient
      exhibited complications of upper and lower respiratory infections several times
      after BMT, all of which subsided within a month. Chemotactic responses toward all
      three chemotactic factors, random mobility, phagocytosis, superoxide (O2-)
      release and bactericidal activity were severely impaired early after
      reconstitution. These neutrophil functions gradually improved with time after
      BMT, and all normalized at 12 months after reconstitution of transplanted bone
      marrow. Both O2- release and bactericidal activity of neutrophils were
      significantly enhanced at 6 and 12 months after marrow reconstitution following
      pretreatment of 50 ng/ml of granulocyte colony-stimulating factor (G-CSF) in
      vitro. These findings suggest that the combined disorders in neutrophil functions
      in early phase after BMT may play an important role in susceptibility to
      bacterial infections until one year after BMT. Administration of G-CSF, which
      potentiates the bactericidal activity of neutrophils, is recommended for
      preventing infectious complications and for treating prolonged and unmanageable
      infections after BMT.

PMID- 9267160
TI  - [Cytomegalovirus disease after hematopoietic recovery in a patient with non
      Hodgkin's lymphoma].
AB  - We report a case of marked cytomegalovirus (CMV)-antigenemia determined by direct
      immunoperoxidase staining using a peroxidase-labeled monoclonal antibody HRP-C7,
      after conventional chemotherapy for malignant lymphoma. A 65-year-old Japanese
      man suffered from unexplained fever, mild liver dysfunction and an abnormal
      shadow in the lung after hematopoietic recovery from intensive chemotherapy for T
      cell non-Hodgkin's lymphoma in the leukemic phase. The assay for CMV-antigenemia
      revealed that he had an active CMV infection. After treatment with ganciclovir
      and gamma-globulin, his symptoms and signs improved with the decrease of CMV
      antigen-positive leukocytes. CMV disease should be considered in these
      situations, and the CMV antigen-detection assay is useful for rapid diagnosis of
      CMV infection.

PMID- 9267161
TI  - [Non-Hodgkin's lymphoma associated with polymyositis].
AB  - A 67-year-old man was admitted to with severe nasal congestion. One year
      previously, he had been suffered from polymyositis (PM) and had been treated with
      prednisolone. Physical examination and computed tomography revealed a mass in the
      upper pharynx. Biopsy revealed non-Hodgkin's lymphoma (diffuse medium, B-cell
      type). Bone marrow aspiration also revealed the infiltration by lymphoma cells.
      The patient achieved a complete remission after combination chemotherapy
      (cyclophosphamide, adriamycin, vincristine, prednisolone). However, one month
      later, he suffered from central nervous system involvement of lymphoma cells, and
      he died of an aspiration pneumonia. Polymyositis/dermatomyositis associated with
      non-Hodgkin's lymphoma is extremely rare.

PMID- 9267162
TI  - [Non-Hodgkin's lymphoma associated with cold agglutinin disease].
AB  - Autoimmune hemolytic anemia (AIHA) complicated with non-Hodgkin's lymphoma (NHL)
      is not unusual. Two cases of NHL associated with cold agglutinin disease were
      reported. Case 1: A 38-year-old man had diffuse medium-sized cell NHL diagnosed
      by cervical lymph node biopsy. The Hb was 7.6 g/dl with a cold agglutinin titer
      of 32,768, and the IgM level was 890 mg/dl (I-specific), so cold agglutinin
      disease (CAD) was suspected. After administration of COP-BLAM therapy, complete
      remission (CR) was achieved along with a decrease in the cold agglutinin titer
      and improvement of anemia. Case 2: A 68-year-old woman had follicular mixed NHL
      diagnosed by inguinal lymph node biopsy. The Hb was 8.2 g/dl with a cold
      agglutinin titer of 51,200, and an IgM level of 920 mg/dl (I specific), thus
      concurrent CAD was suspected. Biweekly COP-BLAM therapy was administered and CR
      was achieved along with a decrease in the cold agglutinin titer and improvement
      of her anemia. In both patients, the cold agglutinin titer decreased after CR was
      achieved suggesting that production of anti-erythrocyte autoantibody was due to
      disturbance of the antibody system by NHL.

PMID- 9267163
TI  - [Malignant lymphoma complicating myelodysplastic syndrome with autoantibody for
      the thyroid gland].
AB  - A 68 year old woman was hospitalized because of cervical lymphadenopathy.
      Hematological data on admission showed anemia, leukopenia with a normal platelet
      count. Serum serological studies revealed polyclonal hypergammaglobulinemia, a
      positive microsome and thyroid test, and positive reaction to antithyroglobulin
      antibody. Microscopic examination of a cervical lymph node revealed malignant
      lymphoma, diffuse large cells of B cell phenotype. The bone marrow smears
      revealed hypercellularity with dysplastic features including pseudo-Pelger and
      other nuclear abnormalities of neutrophils, micromegakaryocytes,
      dyserythropoiesis with megalobastic changes, 60% ring sideroblast and with no
      increase in proportion of blast cells (3.6%). A diagnosis of myelodysplastic
      syndrome (MDS, refractory anemia with ring sideroblast (RARS)) was made.
      Remission of ML obtained with radiation and subsequent systemic chemotherapy with
      CHOP-Bleo regimen, although she died 2.5 yr after the diagnosis due to relapse of
      ML without leukemic transformation of MDS. Although basic disturbances in these
      three conditions are not clear, it is evident that treatment was not concerned
      with the pathogenesis in this case, because the three conditions existed without
      treatment. It may be hypothesized that an initial event which selects a clone of
      stem cells that retains the capacity to differentiate into myeloid and lymphoid
      line would manifest with the features of RARS in the myeloid line and with the
      sort of immunological abnormalities reported in this case. Subsequent events
      select subclones and these progressively lose terminal differentiation,
      culminating as B-cell lymphoma.

PMID- 9267164
TI  - [Idiopathic CD4+ T-lymphocytopenia terminating in Burkitt's lymphoma].
AB  - A 33-year-old male was admitted because of severe neutropenia (55/microliter) in
      1985. A diagnosis of autoimmune neutropenia was not made. CD4+ T-lymphocyte count
      was 128/microliter and CD4/CD8, 0.1, though the titers of immunoglobulins were in
      normal range. Nine times examinations of CD4+ T-lymphocyte count resulted in 5
      times lower counts than 300/microliter between 1985 and 1993. His HIV (type 1 and
      type 2) studies were negative. He suffered from EB virus infection in 1987. The
      titers of VCA-IgG and EA-IgG had been elevated for half a year after that. He was
      operated polyp-like tumors in bilateral nasal cavities on February in 1994. The
      diagnosis was Burkitt's lymphoma that was also demonstrated by in situ
      hybridization using EB virus RNA. He was treated with a modification of COPBLAM
      III, but he died on June in 1994. Autopsy revealed tumor cell infiltrations in
      multiple organs. We suspect that he developed Burkitt's lymphoma 82 months later,
      when he had complicated EB virus infection in condition of idiopathic CD4+ T
      lymphocytopenia caused by unknown origin.

PMID- 9267165
TI  - [Plasma cell leukemia associated with monocytosis].
AB  - A 51-year-old man was admitted to our hospital in December 1993, because of
      fatigue. Peripheral blood tests showed a WBC of 49,400/microliter with 36% plasma
      cells and 35% monocytes, Hb 14.5 g/dl, and Plt 137,000/microliter. Bone marrow
      aspirate revealed hypercellularity with 48.7% plasma cells and 22.4% monocytes.
      Plasma cells in blood were positive for CD38 and PCA-1. Serum calcium, IgA and M
      CSF levels were elevated to 14.1 mg/dl, 2,337 mg/dl and 2.7 ng/ml, respectively.
      Immunoelectrophoresis of serum and urine revealed IgA lambda type M protein and
      lambda type Bence Jones protein, respectively. Rearrangements of immunoglobulin
      heavy chain and light chain were demonstrated by Southern blotting analysis.
      Plasma cell leukemia (IgA lambda type) was diagnosed. He was treated with
      combination chemotherapy and IFN-alpha and achieved complete remission. However,
      he suffered a meningeal relapse in February 1995, and died in April 1996. It
      seems likely that the enhanced production of M-CSF by myeloma cells and/ or
      activated B cells stimulated monocyte production.

PMID- 9267166
TI  - [Umbilical cord blood transplantation for a patient with Diamond-Blackfan
      syndrome].
AB  - A five-year-old girl with Diamond-Blackfan syndrome received cord blood
      transplantation from an HLA-identical sibling. The patient showed pale face at
      birth, and was diagnosed to have Diamond-Blackfan syndrome. She had been treated
      with prednisolone (PSL), high dose of methylprednisolone, erythropoietin, and
      anti-lymphocyte globulin. Despite of these intensive therapies, erythropoiesis
      did not entirely improve, and transfusion of red blood cells had been required
      every third or fourth week until cord blood transplantation. Conditioning regimen
      consisted of thoraco-abdominal irradiation (TAI; 8 Gy), cyclophosphamide (CY; 50
      mg/kg x 4), and anti-thymocyte globulin (ATG; 2.5 mg/kg x 4), Cyclosporin (CyA 3
      mg/kg) was administered for the prophylaxis of graft-versus-host disease (GVHD).
      4.14 x 10 (7)/kg of cord blood mononuclear cells were infused to the patient.
      White blood cell (WBC) and reticulocyte counts increased promptly, but recovery
      of platelet count was delayed. Skin GVHD (grade I) appeared on day +9, which
      responded to the administration of PSL (2 mg/kg). Chromosomal analyses of bone
      marrow cells for sex mismatch revealed complete chimerism on day +14, on day +28
      and thereafter. Umbilical cord blood cells can be an alternative source of
      hematopoietic stem cells for allogeneic transplantation.

PMID- 9267167
TI  - [Leukoencephalopathy probably caused by tacrolimus hydrate after stem cell
      transplantation in a girl with MDS 7 monosomy].
AB  - Leukoencephalopathy probably caused by tacrolimus hydrate after stem cell
      transplantation in a girl with MDS 7 monosomy is reported. The conditioning
      regimen consisted of thiotepa (150 mg/m2 x 4), melphalan (70 mg/m2 x 2) and 12 Gy
      total body irradiation. She received peripheral blood CD34 positive cells (4.17 x
      10(6)/kg) from her HLA-mismatched father and tacrolimus hydrate was used for GVHD
      prophylaxis. Engraftment was rapid and grade 1 acute GVHD of the skin responded
      well to pulse therapy. From day 27 she became irritable and sleepless, and right
      facial convulsions developed on day 37. No abnormality was found in the
      cerebrospinal fluid. Cranial CT findings showed no abnormalities except for low
      density lesions around the bilateral ventricle. Leukoencephalopathy was suspected
      and tacrolimus hydrate was discontinued. Thereafter psychosomatic symptoms
      improved, temporarily however, similar symptoms again developed following
      cyclosporine administration. Therefore we had to halt the administration of both
      tacrolimus and cyclosporine. She died on day 104 because of GVHD and fungal
      infection without recovering from leukoencephalopathy.

PMID- 9267168
TI  - [High fever during the treatment of acute promyelocytic leukemia with all-trans
      retinoic acid].
AB  - A 56-year-old woman was admitted for evaluation of petechiae and acute
      promyelocytic leukemia was diagnosed. Administration of all-trans retinoic acid
      (ATRA) at 60 mg per day was begun. On the same day, high fever was recognized.
      There was no evidence of infection nor other organ dysfunction. Administration of
      steroid caused a resolution of the fever. The same phenomenon was observed three
      times subsequently. High fever was the adverse reaction in this patient during
      the treatment of ATRA, and steroid was dramatically effective.

PMID- 9267169
TI  - Gastric tonometry--quo vadis?

PMID- 9267171
TI  - The current treatment of oesophageal varices.
AB  - The wide range of management options available today are evaluated in this
      article. The advised management policy for acute variceal bleeding includes
      admission to a hospital with an interest in portal hypertension, resuscitation,
      the possible use of pharmacological agents to lower portal pressure, and
      definitive endoscopic therapy (either sclerotherapy or banding). More major
      surgical procedures (i.e. shunts or transection operations or TIPS) should be
      reserved for patients in whom endoscopic therapy falls. Long-term management to
      prevent recurrent variceal bleeding is somewhat more controversial. The options
      for the majority of patients are pharmacological therapy with beta-blockers, or
      repeated endoscopic therapy to eradicate varices, or a major surgical procedure,
      preferably a partial shunt. All patients should be considered for liver
      transplantation although few will ultimately end up as liver transplant
      candidates. Prophylactic therapy prior to a variceal bleed, other than beta
      blockade in selected patients, is unjustified today because of the difficulty in
      identifying high-risk patients.

PMID- 9267170
TI  - Ether Day and the first ether anaesthetics in South Africa.

PMID- 9267172
TI  - Disease profile of colon and rectum carcinoma at Pelonomi Hospital, Bloemfontein.
AB  - A retrospective study evaluated all new cases of colorectal cancer which
      presented over a 7-year period at Pelonomi Hospital, Bloemfontein. The aim of the
      study was to compare patients younger than 40 years with the group older than 40
      years. Most patients presented late, with advanced disease. A high proportion of
      patients were younger than 40 years (32.4%). No significant differences in sex
      ratio, tumour position, differentiation or stage of tumour were detected between
      the two groups. Of note was a high proportion (45%) of right-sided colon cancer
      in both groups. The younger patients did not have more advanced disease at
      presentation than the older group. Their prognosis, when matched stage for stage,
      was similar.

PMID- 9267173
TI  - Symmetrical multifocal liposarcoma.
AB  - Multiple liposarcomas are extremely rare. We report on a patient with liposarcoma
      of the right lower limb who had undergone surgery and radiotherapy 4 years
      previously for a liposarcoma in the left lower limb. An outline of the management
      is discussed and a short review of available literature is given.

PMID- 9267175
TI  - Delayed presentation of congenital diaphragmatic hernia.
AB  - Patients with congenital diaphragmatic hernias (CDH) usually present soon after
      birth with respiratory distress. Occasionally presentation is delayed. Twelve
      patients with delayed presentation (outside the neonatal period) of a total of 91
      with CHD were seen over 17 years (1977-1994). Case records were reviewed to
      identify reasons for late presentation, evidence of morbidity, treatment and
      outcome. Age at presentation ranged from 6 weeks to 30 months (mean 8 months).
      Ten patients were aged 6 months or younger and there was an equal number of boys
      and girls. Seven cases were left-sided, 4 right-sided and 1 was anteriorly placed
      and bilateral. Ten patients presented acutely, 5 with small-bowel obstruction and
      5 with respiratory distress, but all of the latter had a history of previous
      recurrent chest infection. Diagnosis was confirmed by radiographic examination of
      the chest in 10, barium meal in 1 and a 5-month-old patient had an inappropriate
      laparotomy and gastrojejunostomy for duodenal obstruction at an outlying
      hospital. Two had documented normal chest radiographs 3 and 6 months prior to
      diagnosis. Patients who presented with gastro-intestinal symptoms were older
      (mean age 1 year) compared with those with predominantly respiratory symptoms
      (mean age 19 weeks). None had any evidence of bowel strangulation. All were
      repaired via an abdominal approach. A hernial sac was found in half the cases
      (4/7 left and 2/5 right). Five had non-rotation of bowel. Primary repair without
      patch was carried out in all. One child with lung hypoplasia and multiple cardiac
      abnormalities died; the others recovered well. Delay in presentation of CDH is
      not uncommon (14% in this series). Most patients will have respiratory symptoms.
      A normal previous chest radiograph does not exclude the diagnosis. All patients
      with recurrent chest infection should have a contrast meal investigation early
      on. Long-term prognosis is favourable and postoperative morbidity is minimal,
      despite late presentation.

PMID- 9267174
TI  - The value of laparoscopy for impalpable testes.
AB  - Impalpable testes constitute up to 20% of cases of undescended testes and present
      both a diagnostic and a therapeutic problem. Knowledge of testicular site prior
      to orchidopexy is useful in planning surgical strategy. Misdirected blind
      inguinal exploration can be avoided. Many imaging techniques are time-consuming
      and expensive and can neither confidently locate an impalpable testis nor exclude
      its absence. Recently laparoscopy has been advocated as a safe and efficient
      method of identifying presence and site of an impalpable testis. The first stage
      of a divided-vessel orchidopexy may also be performed simultaneously. Fifty
      children with 60 impalpable testes--40 unilateral and 10 bilateral--underwent
      laparoscopic examination prior to groin exploration. In 5 (8%) an inguinal testis
      was found which had been missed on pre-operative palpation. The testis was absent
      in 23 (38%), of whom 13 had a limited negative groin exploration because cord
      structures were seen entering the internal ring. In 30 (50%) an intra-abdominal
      testis was identified; 14 were relocated into the scrotum with a standard
      orchidopexy, 16 required a divided-vessel orchidopexy. In 2 (4%) intra-abdominal
      testicular remnants were removed. There was no operative morbidity. We conclude
      that laparoscopy is a useful technique in the management of children with
      impalpable testes. Open perumbilical insertion of the trochar is a safe method of
      introducing the telescope into the peritoneal cavity. In addition to accurately
      identifying a testis in 60%, 40% were spared the pain and morbidity of an
      extensive groin exploration.

PMID- 9267176
TI  - The management of biliary complications following orthotopic liver
      transplantation.
AB  - OBJECTIVE: Review of the biliary complications following orthotopic liver
      transplantation (OLT) at our institution, and their management and outcome.
      DESIGN: Retrospective study of medical records of 63 patients who underwent 68
      transplant operations. SETTING: The Liver Transplant Unit, Groote Schuur Hospital
      and Red Cross War Memorial Children's Hospital, Cape Town PATIENTS: Six patients
      treated for 9 biliary complications. INTERVENTIONS: Reoperation with biliary
      reconstruction, or non-operative measures by either endoscopic retrograde
      pancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC).
      OUTCOME MEASURES: Clinical outcome and survival following treatment for biliary
      complications. RESULTS: Biliary complications occurred in 8.8% of patients who
      underwent transplantation at our institution. These consisted of strictures in 4
      patients (with leak in 2), bile leak in 1 patient, and unsuspected primary
      sclerosing cholangitis (PSC) of the recipient duct in 1 patient. The mean time
      interval of biliary complications following OLT was 8 weeks (range 3-16). Biliary
      reconstruction was required in 4 patients while 2 patients were treated by
      endoscopic stenting. After a mean follow-up period of 30 months (range 1-64), 4
      patients remained stable, 1 patient developed progressive stricturing of the
      intrahepatic ducts requiring repeated PTC dilatations, and 1 patient experienced
      stent blockages requiring endoscopic stent changes (died of unrelated causes).
      CONCLUSIONS: The rate of biliary complications following OLT at our institution
      compares favourably with literature reports. While biliary reconstruction is
      usually needed, endoscopic stenting appears effective in selected cases of
      biliary stricture and leak. PSC should be excluded prior to transplantation in
      young patients with cryptogenic cirrhosis.

PMID- 9267177
TI  - Penetrating injuries involving the intrathoracic great vessels.
AB  - Forty-four consecutive patients with injuries to the intrathoracic great vessels
      admitted to our department from January 1982 to June 1994 were reviewed
      retrospectively. Forty-two patients (95%) sustained stabwounds and 2 (5%)
      patients had gunshot wounds. The most frequent radiological abnormality was
      mediastinal widening in 26 patients (59%). Eighteen patients (41%) were
      haemodynamically stable on admission with the remainder being unstable (46%),
      agonal (11%) or lifeless (2%). Twenty-two patients (50%) underwent angiography
      with 1 false-negative study. A total of 48 arterial and 16 venous injuries were
      identified with the innominate artery (N = 17, 39% of patients) and left
      innominate vein (N = 8, 18% of patients) the most frequently injured structures.
      Associated injuries to thoracic viscera occurred in 13 patients (30%). Two
      patients required cardiopulmonary bypass to repair their injuries. Arterial
      shunts were not used in any case. Overall mortality was 5% (2/44) and
      complications occurred in 7 patients (16%).

PMID- 9267178
TI  - Wound modulation via sclerotherapy and tissue adhesion. Observations and
      discussion.
AB  - Fluid accumulation in a 'dead space' after surgery or trauma predisposes the area
      involved to delayed healing. The fluid may promote inflammatory mediators and
      other wound-modulating factors, which encourages the continued existence of the
      dead space. Tissue adhesion by means of agents such as tetracyclines has long
      been described. With this concept, tissue adhesion has been accomplished with
      varying success in diverse clinical situations involving non-healing wounds and
      prophylactically in seroma-prone areas. A total of 69 patients were treated and
      monitored. The most impressive response to tetracycline tissue adhesion in this
      study was seen in intra-oral sites, with rapid closure of wounds. More complex
      wounds such as orocutaneous fistulas or wounds of a more chronic nature such as
      pressure sores did respond but took longer to resolve. The lateral thigh was
      found to be the most difficult and unresponsive area to treat (particularly after
      delayed presentation). Successful prophylactic use of tetracycline in seroma
      prone areas (latissimus dorsi/parascapular flaps, etc.) is also described.

PMID- 9267179
TI  - Venous bullet embolism. A case report.
AB  - Venous missile embolism to the pulmonary artery is a rare occurrence and
      controversy persists about the need to remove such a foreign body. This report
      describes a case of bullet embolism from the right common iliac vein to the left
      pulmonary artery. In this case the bullet was not removed.

PMID- 9267180
TI  - Strains of Drosophila melanogaster differ in alcohol tolerance.
AB  - The influence of environmental ethanol on different fitness components and the
      larval activities of some enzymes were studied in three strains of Drosophila
      melanogaster. All three strains carried the AdhS-alphaGpdhF allele combination on
      their second chromosomes while they had unique allele combinations at the Odh and
      Aldox loci on their third chromosomes (strain 1: OdhS-AldoxF; strain 2: OdhF
      AldoxS; strain 3: OdhS-AldoxS). Normal lines and exposure lines, kept on 5%
      ethanol supplemented medium for at least 20 generations, were established from
      each strain and the responses of the two lines to different ethanol
      concentrations were compared. Two survival components were estimated in the
      juvenile life history stages. In addition, the weights of the emerging adult
      males were measured at various concentrations of ethanol. The changes in the
      activities of two enzymes (ADH and alpha GPDH) were also surveyed in the larvae
      after the different ethanol treatments. Strain-specific differences were observed
      in the responses of all investigated traits to ethanol. OdhS-AldoxF larvae seemed
      to be more tolerant to ethanol than the larvae of the other two strains while the
      utilisation of ethanol as energy source appeared to be the least effective in
      this strain. Larvae of the exposure lines had significantly higher tolerance to
      ethanol, and the adult males were heavier, than the ones from the normal lines.
      The enzymatic responses of the two lines to the ethanol treatments were also
      different. ADH activity, fresh male weight, and pupa-to-adult survival seemed
      only to be associated under short-term exposure to ethanol. Ethanol tolerance
      appeared to be independent of the utilisation of ethanol in the larva-to-pupa
      stage.

PMID- 9267181
TI  - FISH mapping of three bovine cosmids to cattle, goat, sheep and buffalo X
      chromosomes.
AB  - Contrary to extensive banding similarities of the autosomes, there are variations
      in the morphology as well as banding patterns of the X chromosomes of various
      species of bovidae family. We used three bovine X chromosome specific cosmid
      clones for fluorescence in situ hybridization mapping on cattle, goat, sheep, and
      river buffalo chromosomes to identify homologous regions in the genomes of the
      four species. The three cosmids (cIOBT 314, 945, and 1489) mapped to well spaced
      locations on buffalo X, and both arms of cattle X chromosome. However, of the
      three probes, cosmids cIOBT 314 and 1489 showed no hybridization signal on any of
      the goat-sheep chromosomes. Incidentally, the two cosmids show correspondence to
      those regions of the buffalo X chromosome which are proposed to be lost during
      the structural reshuffle of the latter, leading to sheep/goat X chromosomes. The
      lack of hybridization signal of the two cosmids in sheep and goat, therefore,
      indicates that these DNA sequences are most likely absent in the two genomes and
      probably correspond to the segments lost during evolution of their X chromosomes.

PMID- 9267182
TI  - A genetic screen for meiotic mutants in mosaic clones of male germ line in
      Drosophila melanogaster.

PMID- 9267183
TI  - The positive wave.

PMID- 9267184
TI  - Ventilatory function in cervical and high thoracic spinal cord injury.
      Relationship to level of injury and tone.
AB  - Weakness and spasticity of chest wall muscles are known to adversely affect
      pulmonary function in spinal cord-injured patients. To test the assertion that
      impaired strength and increased tone contribute to ventilation deficits, 52
      patients with recent acute traumatic cervical and high thoracic spinal cord
      injury underwent complete pulmonary function testing. Regression analyses were
      performed to determine relationships between spinal cord injury level and
      pulmonary function test results and between Ashworth scale tone ratings and
      pulmonary function test results. Level of injury was found to be significantly
      correlated with expiratory reserve volume (and percent predicted expiratory
      reserve volume), residual volume/total lung capacity ratio, and negative
      inspiratory pressure but not with vital capacity, forced expiratory volume in one
      second, forced expiratory volume in one second/vital capacity ratio, inspiratory
      capacity, total lung capacity, functional residual capacity, residual volume, or
      positive expiratory pressure. There were significant correlations between
      Ashworth Scale tone ratings and negative inspiratory pressure but not between
      tone ratings and any of the other pulmonary function test results. It appears
      that muscle strength may be a more important factor than muscle tone in
      determining pulmonary function in spinal cord-injured patients and that both
      strength and tone are closely related to negative inspiratory pressure.

PMID- 9267185
TI  - Mentorship in physical medicine and rehabilitation residencies.
AB  - Mentorship is considered by many authorities as being possibly the most important
      developmental tool for the progression of a professional in training. In recent
      years, progressively increasing support of mentoring programs has been
      documented, especially in business, academia, and overall career development.
      Despite its recognized importance, there is a paucity of literature examining the
      needs of physicians in residency training programs in regard to mentorship. A 21
      item questionnaire was sent to all physical medicine and rehabilitation (PM&R)
      residents in training in United States residency programs in May of 1993. The
      objectives of this survey were 3-fold: to assess interest in mentorship among
      PM&R residents, to determine the effect of preresidency mentorship on candidates
      choosing PM&R as a specialty, and to identify the factors that establish a
      successful mentorship in PM&R residency. A response rate of 36.2% (406/1123) was
      obtained. Analysis of the results indicated that 97.3% (390/401) of the
      respondents were interested in mentorship programs during PM&R residency;
      however, only 28.1% (114/406) had a mentor at the time of the survey. Before
      residency, 35.4% (143/404) of the respondents had a mentor, and of those, 75.9%
      (107/141) indicated that mentorship had a positive effect on their decision to
      choose PM&R as a specialty. Regarding the current mentorship, respondents
      benefited the most in the categories of increased knowledge of PM&R, 72.8%
      (83/114), and improved clinical skills, 65.8% (75/114). The least satisfaction
      was with the mentor's assistance with a research project, 46% (52/113), and with
      the effect of mentorship on the resident's visibility and reputation, 38.6%
      (44/114). Overall resident satisfaction with mentorship was significantly higher
      (P < 0.0001) in mentorships formed by free choice compared with those that were
      formally assigned by the residency program. Success of mentorship significantly
      correlated (P < 0.0001) with frequency of communication between mentor and
      protege, while gender and ethnicity had no effect.

PMID- 9267186
TI  - Impaired phagocytosis of Staphylococcus aureus in complete tetraplegics.
AB  - Accumulating evidence implicates the sympathetic nervous system as a modulator of
      immune function. Immune alteration has been observed in survivors of cervical
      level spinal cord injury, possibly because of dysregulation of the sympathetic
      outflow tracts. The majority of immune studies in the spinal cord-injured
      population have focused on lymphocytes. Because of the high incidence of
      infections in this population, we hypothesized that the immune alteration would
      extend to the cells of the myeloid lineage. This hypothesis was tested by
      analyzing the phagocytic and bactericidal function of circulating neutrophils in
      response to Staphylococcus aureus. A group of ten individuals with complete
      cervical spinal cord injury, a group of eight paraplegics with injuries below the
      majority of sympathetic outflow (T-10 and below), and age- and gender-matched
      controls for each subject were studied. In addition, a psychiatric screening for
      depression was completed by all subjects and controls. Paired t test revealed
      significantly impaired phagocytic ability in the tetraplegic group compared with
      their controls. The paraplegic group did not demonstrate these findings. Our
      results suggest that individuals who have sustained complete cervical spinal cord
      injury have alteration in immune function compared with neurologically intact
      controls, whereas those with lesions at or below T-10 do not. This in vitro
      finding may be related to infection after cervical spinal cord injury. The
      mechanism may involve dysregulation of the sympathetic arm of the autonomic
      nervous system.

PMID- 9267187
TI  - Giant repeater F-wave in patients with anterior horn cell disorders. Role of
      motor unit size.
AB  - Conventional F-wave responses as well as single motor unit F-wave responses
      together with the volitionally recruited motor unit action potentials (MUAP) were
      studied in hand and feet muscles of 10 healthy subjects and 32 patients with
      anterior horn cell disorders. The amplitude of the largest F-wave (Fl) was
      significantly greater in the affected patients compared with healthy subjects.
      Giant repeater F-wave responses "up to 4 mV" were recorded in muscles having
      volitionally recruited giant MUAPs. Although, the group mean percentage of motor
      unit F-wave responses per stimulation in all tested orthodromic MUAPs was
      significantly decreased in amyotrophic lateral sclerosis patients, the group mean
      percentage of motor unit F-wave responses per stimulation in all tested
      orthodromic MUAPs that gave motor unit F-wave response was significantly
      increased compared with healthy subjects. The responding orthodromic MUAP gave
      identical motor unit F-wave response, even for complex polyphasic units. Enhanced
      monosynaptic (H-) reflex, proximal axon reflex (A-wave), and repetitive muscle
      response as possible explanations for the giant F-wave responses could be
      discounted. The electrophysiologic behavior of the giant late responses described
      here fits well with the criteria of F-waves modulated by newly formed distal (and
      or proximal) axonal branching.

PMID- 9267188
TI  - Combined ultrasound, electrical stimulation, and laser promote collagen synthesis
      with moderate changes in tendon biomechanics.
AB  - The biomechanical, biochemical, and ultrastructural effects of a multitherapeutic
      protocol were studied using regenerating rabbit Achilles tendons. The
      multitherapeutic protocol was composed of low-intensity Ga:As laser
      photostimulation, low intensity ultrasound, and electrical stimulation. Achilles
      tendons of 63 male New Zealand rabbits were tenotomized, sutured, immobilized,
      and subjected to the multitherapeutic protocol for five days, after which casts
      were removed and the therapy was continued for nine more days without electrical
      stimulation. The tendons were excised and compared with control tendons.
      Multitherapy treatment produced a 14% increase in maximal strength, a 42%
      increase in load-at-break, a 20% increase in maximal stress, a 45% increase in
      stress-at-break, a 21% increase in maximal strain, and a 14% increase in strain
      at-break. Similarly, multitherapy treatment was associated with an increase in
      Young's modulus of elasticity of 31%, an increase in energy absorption at maximum
      load of 9%, and an increase in energy absorption at load-at-break of 11%.
      Biochemical analysis of the tendons showed an increase of 23% in the total amount
      of collagen in the multitherapy-treated tendons, with fewer mature crosslinks
      (decrease of 6%). Electron micrographs revealed no ultrastructural or morphologic
      changes in the tendon fibroblasts or in the extracellular matrix. The
      improvements measured in tendons receiving multitherapy were consistent but less
      remarkable compared with our earlier works with single modality protocols. The
      results warrant the hypothesis that the beneficial effects of ultrasound and
      laser photostimulation on tendon healing may counteract one another when applied
      simultaneously.

PMID- 9267189
TI  - Submaximal oxygen pulse divided by body weight during incremental exercise test.
AB  - The purpose of this study was to examine whether submaximal oxygen pulse divided
      by body weight (O2 pulse/BW) during an incremental exercise test discriminated
      between trained and untrained men, correlated to left ventricular ejection
      fraction (LVEF) at rest in post-myocardial infarction patients, and was sensitive
      and specific in detecting ventricular dysfunction and mild ventricular
      dysfunction with myocardial ischemia during exercise. Forty-three trained men, 44
      untrained men, and 21 post-myocardial infarction patients pedaled a cycle
      ergometer, with O2 consumption, heart rate, and myocardial ischemia monitored
      during the exercise test. Work rate started at 10 W and increased 10 W/min
      stepwise; the O2 pulse and O2 pulse/BW at 10 through 120 W were calculated. The
      LVEF of the patients was measured at rest using radionuclide ventriculography
      three weeks after myocardial infarction. The results revealed that O2 pulse/BW
      was significantly different between trained and untrained men at 80, 90, 100,
      110, and 120 W, whereas O2 pulse was significantly different only at 110 and 120
      W. Oxygen pulse/BW at 10 W, as well as 30 through 120 W, significantly correlated
      to LVEF in the patients. The three patients with ventricular dysfunction (LVEF, <
      40%) plus the two patients with mild ventricular dysfunction (LVEF between 40 and
      50%) and ST segment depression during exercise all had submaximal O2 pulse/BW
      significantly lower than untrained men (sensitivity, 100%). Among the 11 patients
      with normal ventricular function (LVEF, > 50%) plus the 5 patients with mild
      ventricular dysfunction but no ST segment depression, 13 patients did not have
      submaximal O2 pulse/BW significantly lower than untrained men (specificity, 81%).

PMID- 9267190
TI  - Forces, moments, and accelerations acting on an unrestrained dummy during
      simulations of three wheelchair accidents.
AB  - To determine the magnitude and distribution of the forces, moments, and
      accelerations acting on an individual sitting in a wheelchair during three
      possible accidents occurring while negotiating a sidewalk curb, experimental
      trials were performed in a bioengineering laboratory using a 50th percentile
      Hybrid III dummy seated in a standard wheelchair. A ramp was designed with an
      adjustable incline to allow the wheelchair to reach the edge of a sidewalk height
      platform at the desired forward speed of 2.5 miles per hour (comfortable walking
      speed). The wheelchair velocity was monitored via an optical pickup. Three types
      of accidents were simulated: (1) a wheelchair hitting straight into a curb; (2) a
      wheelchair falling forward straight off a curb; (3) a wheelchair falling
      diagonally off a curb. Each experiment was repeated three times. Each run was
      photographed using high-speed cameras and videotaped from three perspectives:
      frontal, lateral, and overhead. The results were averaged and compared with
      published injury Assessment Values (IAV) and Head Injury Criteria (HIC). Of
      significance were the following results. In the straight into a curb experiments,
      the wheelchair remained upright and the dummy seated. Low magnitude forces (23-73
      N), moments (1-12 Nm), and accelerations (0.2-1 G) were recorded at the neck and
      head. The HIC was low at 0.3. These results were of no clinical significance. In
      the straight off a curb experiments, properly attached footrests prevented the
      wheelchair from toppling over but did not prevent the dummy from falling off the
      wheelchair. Forces (187-4,176 N), moments (3-178 Nm), and accelerations (131-206
      G) of great magnitude were recorded at the head and neck when the dummy fell off
      the wheelchair. These values were above IAV. The HIC was 960. In the diagonally
      off a curb experiments, both the wheelchair and the dummy fell sideways. High
      magnitude forces (274-2,313 N), moments (4-110 Nm), and acceleration (140-236 G)
      were recorded in the head and neck regions. The HIC was 975. These values were
      close to IAV and may signify potential serious injuries.

PMID- 9267191
TI  - Activity levels and the relationship to lung function and nutritional status in
      children with cystic fibrosis.
AB  - Cystic fibrosis is characterized by chronic obstructive lung disease and
      malnutrition. Previous studies have shown that nutritional status and lung
      function are limiting factors for exercise capacity. A reduced exercise capacity
      may in turn diminish activity levels. We evaluated whether the total time spent
      somewhat active (e.g., walking) or active (e.g., biking), as reported by the
      Habitual Activity Estimation Scale, was related to lung function, as evaluated by
      forced expiratory volume in one second (%predicted FEV1), and nutritional status,
      measured as body mass percentile, in 36 children with cystic fibrosis, aged 6 to
      16 years. The Habitual Activity Estimation Scale questionnaires were completed by
      the parents for children younger than 12 years of age and by both the parent and
      the child, independently, for those 12 years and older. Patients had a body mass
      percentile of 99 +/- 15.2% and % predicted FEV1 of 85.7 +/- 20, with no
      differences between boys (15/36) and girls (21/36). Boys spent 8.1 hours and
      girls spent 7.5 hours (P > 0.1) being at least somewhat active. These values are
      similar to those reported for healthy boys and girls. In patients with
      significant lung disease (%predicted FEV1, < or = 75; n = 11), activity level
      (the time spent somewhat active or active) was related to nutritional status (r =
      0.675; P = 0.02) but not to lung function (r = 0.21; P > 0.1). Activity level
      reported by patients 12 years of age and older was on average 24.1% higher (P <
      0.05) than that reported by their parents, but the two reportings were related (r
      = 0.758; P = 0.004). These results suggest that activity level may be restricted
      by nutritional status in those patients with significant air flow limitation. We
      suggest that improving the nutritional status of cystic fibrosis patients may
      prevent decreases in activity levels and quality of life of these affected
      children.

PMID- 9267192
TI  - Rotator cuff repairs in individuals with paraplegia.
AB  - Shoulder pain and dysfunction are common problems among those individuals with a
      spinal cord injury (SCI). Among individuals with SCI who have shoulder pain, the
      prevalence of rotator cuff tears is 65 TO 71%. To date, there has been little
      discussion as to the efficacy of various treatments for shoulder pain used in the
      SCI population. The purpose of this retrospective study was to evaluate the
      outcome of rotator cuff repairs at the Spinal Cord Injury Center (Veterans
      Administration Puget Sound Health Care System). Five patients (six shoulders)
      were identified who had undergone shoulder surgery for rotator cuff tear since
      1987. Four individuals (five shoulders) had large rotator cuff tears, and
      following surgery, none of these repairs resulted in improvement of shoulder
      function or improvement in active range of motion. The one patient with a smaller
      tear limited to the supraspinatus had a successful surgical outcome in that he
      had decreased pain, increased strength, and increased range of motion. There is a
      general lack of epidemiologic information about shoulder pain in individuals with
      paraplegia. There is also a remarkable lack of research as to the functional
      impact of shoulder pain and the outcome of nonsurgical and surgical treatments.
      This case series, drawn from a population of 511 individuals with spinal cord
      injury, demonstrates that poor outcome was more likely in those with
      supraspinatus atrophy, those with upward displacement of the humeral head on x
      ray, and in those with tears involving more than one muscle. There is a need for
      further study of conservative treatment and development of selection criteria for
      those individuals who are being considered for surgery.

PMID- 9267193
TI  - Incidence of fever in the rehabilitation phase following brain injury.
AB  - There appears to be a high incidence of fever after brain injury. The most common
      cause for fever is infection. The incidence of fever occurring as a result of
      hypothalamic thermoregulatory dysfunction after brain injury is less clear. This
      study retrospectively reviewed the charts of 286 subjects with brain injuries.
      Subject subpopulations were divided into traumatic brain injuries, anoxic brain
      injuries, and brain injuries resulting from aneurysmal subarachnoid hemorrhage.
      Fever events were described as any core temperature greater than 99.9 degrees F.
      Most subjects suffered a severe brain injury and had an average acute hospital
      length of stay ranging from 35.4 to 60 days. The average rehabilitation length of
      stay ranged from 38.4 to 45.1 days. Twenty-four percent of subjects experienced
      fevers, with each of the populations having similar occurrence rates. Unexplained
      fever events were found in the traumatic brain injury (7%) and aneurysmal
      subarachnoid hemorrhage (8%) subpopulations only. No unexplained fever event was
      associated with a temperature greater than 100.8 degrees F.

PMID- 9267194
TI  - A case of idiopathic fecal incontinence. Evaluation and management.
AB  - Idiopathic fecal incontinence is a clinical entity described mostly in the
      colorectal surgical literature and seldom encountered by the physiatrist.
      Evidence exists suggesting neuropathic injury to the external anal sphincter.
      Several reports have linked this syndrome to the descending perineum syndrome. A
      final answer to this diagnostic puzzle is yet to be found. This article presents
      a case of probable "idiopathic" fecal incontinence presenting during an
      evaluation for low back pain. Full evaluation yielded a denervating lesion of
      unknown etiology to the pudendal nerve. The patient was managed with a bowel
      program without success. Because physiatrists often find themselves managing
      cases of neurogenic bowel or bladder, it is important for the physiatrist to have
      a thorough understanding of idiopathic fecal incontinence. A discussion of the
      differential diagnosis and management of fecal incontinence is included.

PMID- 9267196
TI  - A review of graduate medical education funding, 1997.

PMID- 9267197
TI  - Evaluation of musculoskeletal disability: current concepts and practice.

PMID- 9267195
TI  - Amyotrophic lateral sclerosis. Successful treatment of mucous plugging by
      mechanical insufflation-exsufflation.
AB  - Bronchial mucous plugging is the main precipitating factor of acute respiratory
      failure for patients with neuromuscular disease. Manually assisted coughing and
      mechanical insufflation-exsufflation can effectively eliminate airway secretions
      without resorting to tracheal intubation provided that bulbar muscle function is
      sufficient to permit assisted peak cough flows of 160 l/min or greater. We now
      report successful use of mechanical insufflation-exsufflation to prevent acute
      respiratory failure for a patient with amyotrophic lateral sclerosis with no
      measurable peak cough flow.

PMID- 9267198
TI  - Team decision making in rehabilitation.

PMID- 9267199
TI  - We are USA.

PMID- 9267200
TI  - Magnesium sulfate: is that the right dose?

PMID- 9267205
TI  - Nondrug measures for painful procedures.

PMID- 9267203
TI  - MI risk in young women.

PMID- 9267206
TI  - Cannulating central venous access devices.

PMID- 9267207
TI  - Posttraumatic stress disorder: how to support healing.

PMID- 9267208
TI  - Managing outpatient cardiac catheterization.

PMID- 9267209
TI  - Clinical snapshot: ulcerative colitis.

PMID- 9267210
TI  - Employing prevention in practice.

PMID- 9267211
TI  - Emergency! Retinal detachment.

PMID- 9267212
TI  - What Grandma Clara wanted. She taught her family that accepting death with
      dignity is part of embracing life.

PMID- 9267214
TI  - Getting published.

PMID- 9267213
TI  - Despite shifting prospects, nursing grads are optimistic.

PMID- 9267215
TI  - When the patient is a racist.

PMID- 9267216
TI  - A SANE approach to sexual assault.

PMID- 9267217
TI  - Why this course of treatment?

PMID- 9267218
TI  - Treatment plan rationale questioned.

PMID- 9267219
TI  - Another possible etiology for anterior open bite?

PMID- 9267220
TI  - Fluoride release from ligature ties.

PMID- 9267221
TI  - Root resorption--long-term outcome.

PMID- 9267222
TI  - Nonsurgical treatment of a skeletal vertical discrepancy with a significant open
      bite.
AB  - A case report of a patient who exhibited with a skeletal Class II, dental Class I
      malocclusion with maxillary right first molar to maxillary left first molar open
      bite. A hyperdivergent cranial base/mandibular plane angle is presented.
      Maxillary-mandibular arch form and arch width discrepancies, a low labial frenum,
      multiple diastemas, and mandibular dental protrusion were present. A history of
      thumb sucking was evident. Active tongue thrusting and inadequate tongue posture
      at the time of treatment were documented. The patient was treated without
      extraction with an 0.022-inch edgewise appliance. A modified tongue crib with a
      palatal button was used until stable bite closure was achieved. Ideal overbite
      and overjet relationships were established. A Class 1 molar and canine occlusion
      was obtained. The transverse discrepancy was solved, and excellent dentofacial
      esthetics were achieved. Posttreatment records for 38 months document the
      stability of the treatment result. [This case report was presented to the
      American Board of Orthodontics in partial fulfillment of the requirements of the
      certification process conducted by the Board.

PMID- 9267223
TI  - The effect of different bonding and debonding techniques on debonding ceramic
      orthodontic brackets.
AB  - Previous studies have indicated that different bonding and debonding techniques
      affect the removal or detachment of polycrystalline ceramic brackets that use a
      mechanical mechanism of bonding to resin. The delamination type debonding forces
      have been shown to be more effective, compared with twisting and tensile type
      forces. Further, polycrystalline brackets bonded by the indirect techniques
      debond leaving minimal filled resin on the tooth surface and hence cleanup and
      enamel damage are minimized. The purpose of this research was to compare the
      effects of three bonding and debonding techniques on debonding two types of
      ceramic brackets, using different modes of bonding. The monocrystalline bracket
      used the chemical and the polycrystalline bracket used the mechanical mechanisms
      for bonding respectively. Brackets were bonded to 180 freshly extracted bovine
      teeth, divided into two groups of 90 each, based on the bracket employed, i.e.,
      monocrystalline and polycrystalline brackets. These brackets were bonded with the
      direct and two different indirect bonding methods: the conventional indirect
      method (modified Thomas) and the indirect technique that used a thermally cured
      resin. Each bonding group was further divided into three groups of 10, based on
      the type of debonding technique used, i.e., lift off, delamination, and twisting.
      The variables evaluated were bracket failure and remnant adhesive on debonding.
      The data were subjected to an analysis of variance to determine existence of
      significant differences, followed by multiple comparisons of means. Bracket
      failure or fracture was significantly affected, based on the bonding technique
      and the debonding technique for the monocrystalline at p < 0.0001 and the
      polycrystalline ceramic brackets at p < 0.001 and p < 0.05, respectively. Remnant
      adhesive was significantly affected by bonding and debonding techniques for the
      polycrystalline brackets at p < 0.0001. Remnant adhesive was significantly (p <
      0.01) affected by the bonding technique for the monocrystalline brackets. The
      delamination debonding technique combined with the thermal-cured indirect bonding
      technique was shown to be a safe combination for debonding both types of ceramic
      brackets. Therefore both bonding and debonding techniques significantly affect
      bracket failure or fracture and remnant adhesive of ceramic orthodontic brackets
      during the debonding procedure.

PMID- 9267224
TI  - Evaluation of frictional resistance in esthetic brackets.
AB  - The purpose of this study was to measure the frictional forces generated between
      composite, ceramic, and metal brackets and selected wire alloy-size combinations
      with elastomeric and stainless steel ligatures in a dry environment. Four types
      of composite, one ceramic, one sapphire, and one metal bracket were tested with
      stainless steel, nickel-titanium, and beta-titanium wires. The testing was
      performed with two wire sizes in the 0.018-inch slot brackets and three wire
      sizes in the 0.022-inch slot bracket. The recently introduced composite brackets
      were found to offer lower frictional resistance than the ceramic and stainless
      steel brackets, regardless of the wire size, wire alloy, and type of ligation.
      The wire alloy with the least friction was stainless steel, followed by beta
      titanium and nickel-titanium. Mean variability in friction, as reflected by the
      magnitude of the standard deviations, was 2.7 to 3 times more with the stainless
      steel ligation than the elastomeric ligation.

PMID- 9267225
TI  - Iliac apophyseal cartilage augmentation of the deficient piriform rim and maxilla
      in alveolar cleft grafting.
AB  - This article presents a new approach to cleft lip and cleft palate repair, where
      the retained bulk of alveolar cleft grafts is augmented by simultaneous cartilage
      augmentation of the deficient maxilla. Nine patients who provided 10 cleft sites
      underwent secondary bone grafting of the clefted alveolus by this technique. This
      study evaluates the following: (1) the postoperative esthetic results, (2) the
      quantity of bone in the grafted area, and (3) the provision of bone support for
      unerupted teeth, for teeth adjacent to the cleft, and for orthodontic tooth
      movement when the secondary bone grafting of the cleft is integrated with the
      onlay augmentation of the deficient maxilla. Photographic and radiographic
      investigations were undertaken. The photographic evaluation showed that all
      patients exhibited improved facial esthetics in the area of the cleft,
      particularly in the paranasal area of the maxilla; improved alar base support,
      symmetry of the columella, and less deviation of the tip of the nose were seen.
      The radiographic evaluation indicated the following: (1) the average percentage
      of the alveolar bone height of the grafted area was equal to 76% of the normal
      side; (2) nine canines erupted or were erupting through the grafted area; there
      were no adequate records to evaluate the fate of the remaining canine; (3) no
      teeth involved in the cleft area were ankylosed, because of inadequate records,
      so evaluators could not determine the status of one tooth; (4) all patients had
      adequate quantity of bone for orthodontic tooth movement through the grafted
      area; and (5) the periodontal support of the teeth involved in the cleft was
      adequate.

PMID- 9267226
TI  - Assessment of pretreatment orthodontic patients using the BANA test. N-benzoyl-DL
      arginine-naphthylamide.
AB  - Ninety-two subjects were tested before orthodontic mechanotherapy for the
      presence of three putative periodontopathogens-Porphyromonas gingivalis,
      Treponema denticola, and Bacteroides forsythus-with the BANA test (PerioScan Oral
      B). The sample ranged from 9 to 16 years, with a mean age of 13.1 years, and
      consisted of 51% girls and 49% boys; 48% African American, 46% white, 4% Asian,
      and 2% Hispanic. Unlike other BANA studies that examined children and adolescents
      with a 15-minute incubation time, this research used a 5-minute incubation time
      to increase the specificity and to reduce the false positives obtained from the
      PerioScan cards. No statistically significant difference was found between the
      age, gender, or race of the patients and the levels of the three putative
      periodontopathogens. A Friedman two-way analysis of variance assessed the BANA
      levels for three groups of teeth: molars, incisors, and premolars. The central
      incisors and first molars had a significantly higher percentage of positive BANA
      readings than the first premolars at p < or = 0.05. The clinical importance of
      this finding has yet to be determined, however, because the central incisor and
      first molar are the first permanent teeth to erupt, a possible association
      between dental emergence time and the rate of infection with various organisms
      may be postulated. In a pilot study, 10 patients from a statistically comparable
      pretreatment group were assessed longitudinally at two separate collection times
      separated by 4 months. The Wilcoxon signed rank test indicated no significant
      changes in these patients over the 4-month period.

PMID- 9267227
TI  - Late lower arch crowding in relation to soft tissue maturation.
AB  - Changes in lower arch space condition and incisor inclinations were measured in
      relation to changes in the cross-sectional area and separation of the lips in
      habitual posture in 23 boys and 23 girls between the ages of 12.5 and 15.5 years.
      Correlation analysis revealed no direct relationship between the increase in
      lower arch crowding and the changes in lip size and position. In girls, the
      increase in lower arch crowding was associated to some extent with retroclination
      of the upper incisors and an increase in the interincisal angle. A very tenuous
      relationship was found between changes in the upper lip size and position and
      changes in incisor angulation.

PMID- 9267228
TI  - Cephalometric landmarks identification and reproducibility: a meta analysis.
AB  - To assess the magnitude of cephalometric landmarks identification error, we
      performed a Meta analysis on six pertinent studies. We outline the procedures
      used to compare and integrate the findings of these-studies. The results are a
      measure of systematic and random errors involved when locating landmarks on
      lateral head films. They are presented as standard mean errors and 95% confidence
      intervals for the repeatability and reproducibility of 15 cephalometric landmarks
      commonly used in growth analysis.

PMID- 9267230
TI  - Role of pharyngeal length in patients with a lack of overbite.
AB  - Anterior open bites may be localized dental manifestations, which are caused by
      habits or skeletal disharmony, with or without functional aberration. Previous
      studies suggest various associations between open bites and underlying etiologic
      factors. We hypothesize that respiratory efficiency may be associated with
      anterior open bites. Under the assumption that breathing efficiency of the
      oropharynx and hypopharynx may be related to pharyngeal airway length, a
      cephalometric variable, vertical airway length (VAL), was measured on lateral
      cephalograms obtained from a total of 58 subjects with, so called, "open bite
      tendencies" (hereafter, open bite tendency). By means of the variable VAL, the
      association between pharyngeal length and open bite was investigated. In
      addition, the difference between actual open bite and open bite tendencies was
      also examined. The samples were randomly collected under stringent selection
      criteria from an existing database. A series of statistical analyses, such as
      unpaired t test, multiple regression, and discriminant analysis, was used to test
      the proposed hypothesis. The study found that none of the open bite tendency
      indicators used can segregate open bite subjects from nonopen bite subjects. The
      obtained discriminant function clearly divides the samples into two groups, i.e.,
      open bite group and nonopen bite group, which were based on VAL and lower facial
      height. The study concludes that, first, an open bite tendency may be a different
      entity from an actual open bite or may be a misconceptualized term. Second,
      pharyngeal length may be a convenient indicator to diagnose open bite. We
      speculate that open bite may be different from an open bite tendency in
      pharyngeal length.

PMID- 9267229
TI  - Comparison of the effects of passive posterior bite-blocks with different
      construction bites on the craniofacial and dentoalveolar structures.
AB  - Posterior bite-blocks that are used in the early treatment of skeletal open bite,
      produce a forward and upward mandibular rotation by transmitting the masticatory
      muscle forces to the buccal dentoalveolar regions and preventing their vertical
      growth. Increasing the vertical dimension of the face artificially causes
      skeletal adaptations to occur not only in the dentoalveolar region but also in
      the other regions of the craniofacial complex. The affects of passive posterior
      bite-blocks, constructed in two different heights, were investigated for two
      treatment groups, in comparison to an untreated control group. Two treatment
      groups comprised of 25 growing patients, who had skeletal open bite and
      skeletal/dental Class I or Class II malocclusions, and one control group
      consisting of 14 growing patients were used. These groups were matched concerning
      their age, sex, and vertical and sagittal skeletal cephalometric and dental
      characteristics. Passive posterior bite-blocks of 5 and 10 mm heights were
      applied to the subjects of the treatment groups respectively for 18 hours per
      day. Untreated control subjects were observed for 7 to 9 months. The findings of
      this study revealed that the downward and backward mandibular rotation continued
      in the control group, increasing the lower facial height significantly, whereas
      in the treatment groups, the skeletal open bite was treated and the mandible
      rotated upward and forward. The increase of the height of the posterior bite
      blocks had a significant effect on the anterior mandibular rotation and in the
      increase of the gonial angle.

PMID- 9267231
TI  - Attractive magnets for orthodontic extrusion of crown-root fractured teeth.
AB  - A subgingival crown-root fracture presents the clinician with a difficult
      restorative problem, including reaching the fracture line, and is complicated by
      the need to maintain the periodontal tissues in good health. The treatment
      options up to now have usually been limited to extrusion of the remaining root
      with a conventional orthodontic appliance, surgical intraalveolar transplantation
      of the root or extraction with bridge replacement. In this report, a new method
      of orthodontic extrusion with attractive magnets is presented. One or two
      neodymium-iron-boron magnets were attached to the remaining root and a second,
      larger neodymium-iron-boron magnet was incorporated in a removable appliance. The
      roots were extruded 2 to 3 mm with a force range from 50 to 240 cN during a
      treatment period of 9 to 11 weeks. Good force control at short distances, no
      friction, and no material fatigue of permanent rare earth magnets resulted in
      successful rapid extrusion. No evidence of soft tissue dehiscences, aberrant
      tooth mobility, or root resorption was found.

PMID- 9267232
TI  - A longitudinal study of tooth wear in orthodontically treated patients.
AB  - The primary objective of this study was to determine whether there is a
      relationship between incisal/occlusal tooth wear during the mixed dentition and
      subsequent wear of the adult dentition. Pretreatment orthodontic records taken
      during the mixed dentition (T1), as well as follow-up records taken an average of
      20 years later (T2), were available for 223 orthodontically treated patients.
      Incisal/occlusal tooth wear was measured on a tooth-by-tooth basis from T1 and T2
      stone casts with a four-category scoring system. Multiple regression analysis (R2
      = 0.33) indicated that wear could be predicted at a given age during adulthood
      from wear observed on the deciduous mandibular canines and molars at T1 (p <
      0.0001). This predictive relationship was modified by the age at which the T1
      wear was observed (p = 0.029) and possibly by the sex of the patient (p = 0.10).
      These results indicate that adult tooth wear is not independent of the tooth wear
      that occurred as a child. Bruxism is suggested as a possible common etiologic
      mechanism that may account for the relationship between childhood and adult tooth
      wear.

PMID- 9267233
TI  - Bond strength of visible light-cured glass ionomer orthodontic cement.
AB  - In this in vitro study, tensile strength tests were conducted with a visible
      light-cured glass ionomer cement (Fuji Ortho LC, GC America Inc.) bonded to
      extracted teeth under six different enamel surface conditions: (1) dry nonetched,
      (2) moist etched, (3) moist nonetched, (4) moist nonetched rebonded, (5)
      moistened with saliva substitute, and (6) moistened with human saliva. Two resin
      adhesives (Rely-A-Bond and Phase II, Reliance Orthodontic Products) were applied
      to dry and etched enamel and served as control agents. The glass ionomer cement
      approached the strength observed for resin adhesives and required the presence of
      moisture on the enamel surface for optimal performance.

PMID- 9267234
TI  - Cervical neckgear--villain or savior?
AB  - An understanding of growth and development and the effect our appliances have on
      a person's growth and development is necessary in the selection of the
      therapeutic appliances we choose to use, out of the multitude available. Timing
      of treatment is also important in effecting positive changes in skeletal and
      dental relationships. Early treatment to correct skeletal discrepancies and gain
      arch length can allow for an increase in nonextraction therapy. Cervical
      extraoral appliances, maxillary fixed expansion appliances, and mandibular labial
      "E" arches can be used early to effectively reduce of skeletal discrepancies and
      to gain arch length without the fear of rotating the mandible down and back,
      permanently increasing the mandibular plane angle. Case reports are presented to
      illustrate the beneficial changes that can occur with early treatment with these
      appliances.

PMID- 9267235
TI  - The functional matrix hypothesis revisited. 2. The role of an osseous connected
      cellular network.
AB  - Intercellular gap junctions permit bone cells to intercellularly transmit, and
      subsequently process, periosteal functional matrix information, after its initial
      intracellular mechanotransduction. In addition, gap junctions, as electrical
      synapses, underlie the organization of bone tissue as a connected cellular
      network, and the fact that all bone adaptation processes are multicellular. The
      structural and operational characteristics of such biologic networks are outlined
      and their specific bone cell attributes described. Specifically, bone is "tuned"
      to the precise frequencies of skeletal muscle activity. The inclusion of the
      concepts and databases that are related to the intracellular and intercellular
      bone cell mechanisms and processes of mechanotransduction and the organization of
      bone as a biologic connected cellular network permit revision of the functional
      matrix hypothesis, which offers an explanatory chain, extending from the
      epigenetic event of muscle contraction hierarchically downward to the regulation
      of the bone cell genome.

PMID- 9267236
TI  - Creating a World Wide Web site for the orthodontic office.

PMID- 9267237
TI  - Litigation, legislation, and ethics. Am I my brother's keeper?

PMID- 9267238
TI  - Mycobacterium marinum skin infection successfully treated with levofloxacin.

PMID- 9267239
TI  - Reliability of the histopathologic diagnosis of melanocytic dysplasia. The
      Dysplastic Nevus Panel.
AB  - OBJECTIVE: To determine the reliability of the histopathologic diagnosis of
      melanocytic dysplasia among diverse dermatopathologists who had no joint
      training, agreed to abide by predetermined criteria, and who were provided
      reference photomicrographs illustrative of the criteria. DESIGN, SETTING, AND
      PARTICIPANTS: A stratified random sample of 112 melanocytic tumors were chosen
      from the files of the pathology department of a large staff-model health
      maintenance organization. The original diagnoses included typical and dysplastic
      melanocytic nevi and melanoma. A single representative slide for each case was
      interpreted independently by each of the 5 panel dermatopathologists and 2
      melanoma specialists. They had no prior knowledge of the original diagnosis or
      the diagnoses of the other panel members. INTERVENTIONS: None. MAIN OUTCOME
      MEASURES: Interrater reliability was measured by intraclass and Pearson
      correlation coefficients. Each case was graded on a 5-point scale from no
      dysplasia to melanoma. RESULTS: The intraclass correlation among the panel
      members was 0.67 (95% confidence interval, 0.59-0.73). The Pearson correlations
      of each of the 5 panel dermatopathologists with the mean of the 2 melanoma
      specialists ranged from 0.67 to 0.84, and the correlations of the mean of the
      panel with the 2 melanoma specialists were 0.79 and 0.82; the mean reading of the
      melanoma specialists correlated 0.89 with the mean panel reading. Apparent
      protocol violations occurred in 6.5% of the readings. CONCLUSIONS: Agreement was
      substantial to excellent for the histopathologic diagnosis of 112 melanocytic
      tumors by dermatopathologists. Using predetermined criteria, melanocytic
      dysplasia can be reproducibly graded among diverse general dermatopathologists.

PMID- 9267241
TI  - Ultrasound examination of hair follicles in hidradenitis suppurativa.
AB  - OBJECTIVE: To describe the in vivo skin echostructure, hair follicle shape, and
      dermal thickness in hidradenitis suppurativa. DESIGN: Qualitative and
      quantitative assessment of high-frequency (20-MHz) B-mode ultrasound images of
      lesional and paralesional skin. SETTING: University hospital. PATIENTS: Age- and
      sex-matched outpatients with hidradenitis suppurativa (n = 15) and healthy
      control subjects (n = 13). Median age was 34 years (range, 31-38). RESULTS:
      Clinically normal paralesional hair follicles in hidradenitis have an abnormal
      shape. The follicles appear to be wider in the deep dermis, the difference being
      statistically significant in the genitofemoral region (P = .007). Patients with
      hidradenitis have larger follicles in the axilla than controls (P = .002). Mature
      acne and hidradenitis lesions are indistinguishable, but both are different from
      epidermal cysts. Mean axillary and genitofemoral skin was significantly thicker
      in patients than in controls. CONCLUSIONS: In vivo ultrasonography shows
      characteristic differences in the shape of hair follicles in hidradenitis. The
      general underlying abnormalities appear to occur in the deep part of the
      follicle. The mature lesions are indistinguishable from acne, but are clearly
      different from epidermal cysts. A thickened skin may play a pathogenic role in
      the development of hidradenitis.

PMID- 9267240
TI  - Lichen planus-like histopathologic characteristics in the cutaneous graft-vs-host
      reaction. Prognostic significance independent of time course after allogeneic
      bone marrow transplantation.
AB  - BACKGROUND: The discrimination between acute and chronic graft-vs-host disease
      (GVHD) after allogeneic bone marrow transplantation (BMT) is important because
      the treatment regimens and prognosis differ. OBJECTIVES: To identify whether
      accepted histopathologic criteria of a graft-vs-host reaction (GVHR) alone or in
      combination accurately reflect clinical phase of disease, to correlate patterns
      with clinical outcome, and to identify any concordance between inflammation and
      epidermal changes of a GVHR. DESIGN: Skin biopsy specimens were analyzed
      according to histologically defined standards. SETTING: This study was performed
      in a tertiary care hospital. PATIENTS: One hundred seventy-three skin biopsy
      specimens (10 days before to 1326 days after BMT) from 83 patients undergoing
      allogeneic BMT for various malignant neoplasms were selected for study. A
      consecutive 12-month sample was used. MAIN OUTCOME MEASURES: The main measures in
      this study were statistical correlations between histopathologic findings and
      time after BMT, the outcome of BMT, and the correlations between selected
      histopathologic criteria. RESULTS: Fully evolved histologic features of chronic
      lichenoid GVHR in the specimens occurred across a wide time range (33-832 days
      after BMT) and were associated with a 5.6-fold increased risk for death (P = .02)
      from GVHD. Histologic features of acute GVHR in the specimens also occurred
      across a wide time range (14-481 days after BMT) and were associated with a 2.2
      fold increased risk for death; this finding was not statistically significant (P
      = .11). Inflammation of the upper dermis was significantly associated with
      acanthosis and epidermal cell necrosis (P < .001 and P < .001, respectively, for
      bandlike pattern), confirming the importance of this finding as a criterion for
      the diagnosis of a GVHR. Blinded evaluation of a subset of specimens for the
      diagnosis of acute vs chronic GVHR resulted in wide interobserver variation.
      CONCLUSIONS: This study demonstrates the following: specific histologic
      parameters in skin biopsy specimens do not consistently separate acute from
      chronic GVHD as defined by days after BMT; independent of time course, fully
      evolved histopathologic characteristics of a lichen planus-like GVHR is
      associated with a greater likelihood of death from GVHD; and identification of
      upper dermal inflammation correlates with the epidermal features of GVHR and
      should be included in the diagnostic scheme.

PMID- 9267243
TI  - Critical effects of intense sun exposure on the expression of epiluminescence
      microscopy features of acquired melanocytic nevi.
AB  - BACKGROUND: Current knowledge of the histologic counterparts of epiluminescence
      microscopy (ELM) features in pigmented skin lesions is limited. As a particular
      aspect of this problem, the transient effects of intense sun exposure on the
      morphological characteristics of melanocytic nevi may influence the expression of
      ELM features as well as the demonstration of stable and consistent histologic
      correlates. OBSERVATIONS: Forty melanocytic nevi from 11 subjects living in
      Northern Italy were examined by digital ELM before and after 5 to 13 days of sun
      exposure at latitudes of 5 degrees north to 3 degrees south. A number of
      multifaceted changes were observed. In particular, 3 lesions showed the
      expression of some structures compatible with radial streaming, pseudopods, and
      gray-blue areas. These features are considered to have often severe histologic
      correlates. In a third image, obtained 5 to 6 weeks later, they showed partial or
      total regression. Another case showed a massive regression of the pigment network
      as a result of a progressive inflammatory reaction with marked asymmetry in the
      distribution of pigmentation. CONCLUSIONS: Digital ELM has the potential to
      detect subtle changes in the structure of nevi after intense sun exposure. The
      transient observation of certain ELM features often associated with severe
      histologic substrates casts doubts on the ability of ELM to characterize sun
      exposed nevi by a single examination.

PMID- 9267242
TI  - Examination of baseline levels of carboxypeptidase N and complement components as
      potential predictors of angioedema associated with the use of an angiotensin
      converting enzyme inhibitor.
AB  - OBJECTIVE: To determine if mean levels of complement components and
      carboxypeptidase N differed when comparing patients who exhibited angioedema
      following angiotensin-converting enzyme inhibitor therapy to those who received
      angiotensin-converting enzyme inhibitor therapy but did not have angioedema.
      DESIGN: Case-control study nested within an 8-week, open-label study of the use
      of quinapril hydrochloride for hypertension in 12275 patients. SETTING:
      Multicenter, with sites throughout the United States. PATIENTS: Of the 36
      patients with angioedema described, 22 participated in the study. They were
      matched to 48 controls by age, sex, race, length of follow-up, and geographical
      region. INTERVENTION: All patients received quinapril therapy prior to
      participation in this case-control study. MAIN OUTCOME MEASURES: Levels of
      carboxypeptidase N, total hemolytic complement, C1 esterase inhibitor, and C4,
      along with questionnaire data, including a history of angioedema-like episodes
      and family history of angioedema. RESULTS: The 22 patients had significantly
      lower mean levels of carboxypeptidase N (kininase I) (P = .03) and C1 esterase
      inhibitor (P = .04) compared with the 48 matched controls, but all mean values
      were within normal laboratory ranges. A history of prior angioedema-like episodes
      was associated with an approximate 6-fold increase in the subsequent risk of
      angioedema following angiotensin-converting enzyme inhibitor therapy.
      CONCLUSIONS: Small differences in levels of carboxypeptidase N or C1 esterase
      inhibitor may contribute to an increased risk of angioedema with angiotensin
      converting enzyme inhibitor therapy. Given the large overlap in the distributions
      of carboxypeptidase N and C1 esterase inhibitor levels, prior testing could not
      be used to evaluate angioedema risk for an individual patient considering
      angiotensin-converting enzyme inhibitor therapy. A history of prior angioedema
      like episodes was associated with increased risk, but this result should be
      interpreted with caution because of possible recall bias.

PMID- 9267244
TI  - Viral folliculitis. Atypical presentations of herpes simplex, herpes zoster, and
      molluscum contagiosum.
AB  - BACKGROUND: Viral folliculitis is an infrequently reported entity. The patients
      described herein were seen over a 12-year period of practice in a referral
      dermatologic setting. The cases involve a variety of viral infections limited to
      the hair follicle. OBSERVATIONS: We describe 5 patients with a variety of viral
      folliculitides: 2 with herpetic sycosis caused by herpes simplex; 1 with herpex
      simplex folliculitis (this patient also had human immunodeficiency virus); 1 with
      herpes zoster without blisters; and 1 with molluscum contagiosum. CONCLUSIONS:
      These 5 cases demonstrate that viral folliculitis has varied causes and
      presentations. Clinicians should consider viral agents in the differential
      diagnosis of superficial infectious folliculitis, especially in cases that are
      refractory to antibacterial or antifungal therapy.

PMID- 9267245
TI  - Resolution of recalcitrant molluscum contagiosum virus lesions in human
      immunodeficiency virus-infected patients treated with cidofovir.
AB  - BACKGROUND: Molluscum contagiosum virus (MCV) causes cutaneous skin growths that
      mainly affect children, sexually active adults, and immunocompromised
      individuals. Lesions of MCV in patients infected with human immunodeficiency
      virus can be large and numerous, and response to available treatments is often
      unsatisfactory. OBSERVATIONS: We describe 3 men infected with human
      immunodeficiency virus who presented with extensive MCV lesions that were not
      responsive to various treatments. Patient 1 demonstrated dramatic clearing of his
      MCV lesions when intravenous cidofovir therapy was started for his treatment
      resistant bilateral CMV retinitis and because of cidofovir's possible activity
      against MCV. In case 2, cidofovir was compounded as a 3% cream in a combination
      vehicle (Dermovan) for extensive facial involvement, and complete resolution of
      MCV was seen after 1 month of therapy. In case 3, intravenous cidofovir therapy
      was started both for CMV retinitis and in an attempt to clear 90% facial MCV
      involvement; after 1 month of treatment, all clinical evidence of MCV had
      resolved. All 3 patients remain clear of recurrence. CONCLUSIONS: Cidofovir, a
      nucleotide analog of deoxycytidine monophosphate, appears to have contributed to
      clearing of advanced MCV lesions in these 3 patients, thus providing suggestive
      evidence of clinical activity against MCV. Controlled trials of cidofovir therapy
      for MCV in persons infected with human immunodeficiency virus are warranted.

PMID- 9267246
TI  - Nonpigmented dysplastic melanocytic nevi.
AB  - BACKGROUND: Dysplastic melanocytic nevi (DMN) are thought to represent a clinical
      and histologic bridge between common pigmented nevi and superficial spreading
      malignant melanoma. The following clinical criteria for DMN were established to
      aid in the proper identification of these lesions: irregular perimeter, size
      exceeding 5 mm in diameter, background erythema, and variegated color (shades of
      browns, tans, blacks, and reds). Histologic features include basilar melanocytic
      proliferation with nuclear atypia, a patchy lymphocytic infiltrate with
      concentric eosinophilic fibroplasia, and lamellar fibroplasia. To our knowledge,
      there have been no previously reported cases of uniformly nonpigmented DMN.
      OBSERVATIONS: A 31-year-old brown-haired, browneyed white woman with no personal
      or family history of either DMN or melanoma presented for evaluation of numerous,
      discrete, nonindurated, 2- to 5-mm-diameter, nonpigmented macules and slightly
      elevated papules that had appeared in a truncal distribution over the course of
      several years. Microscopic examination of these lesions showed lentiginous
      epidermal hyperplasia and disordered proliferation with variable cellular atypia
      of intraepidermal melanocytes. CONCLUSIONS: Nonpigmented, nonindurated, macular
      or slightly elevated papular lesions may represent nevi with features of
      dysplasia. In light of the significant risk of malignant melanoma that is
      associated with pigmented varieties of dysplastic nevi, it is essential that
      clinicians consider nonpigmented DMN in the differential diagnosis of entities
      that present as hypopigmented macules.

PMID- 9267247
TI  - Theoretical and empirical arguments in relation to elective lymph node dissection
      for melanoma.
AB  - Nearly a century of clinical inquiry has failed to incontrovertibly resolve the
      question of whether elective lymph node dissection is therapeutically beneficial
      in the management of clinically localized melanoma. The controversy has been
      renewed by a recent interim update from the Intergroup Melanoma Surgical Program,
      sponsored by the National Cancer Institute, which has indicated a small survival
      benefit in a narrowly defined subgroup of patients with primary melanoma. That
      report stimulated this review of the data, which are presented in the historical
      context that originally prompted the Intergroup study. Case selection bias has
      intractably hindered firm conclusions from the numerous nonrandomized studies of
      elective lymphadenectomy. The two original randomized trials that were executed
      during the 1970s failed to uncover any significant effect of the procedure on
      survival. Definitive conclusions from the recent Intergroup report are limited by
      the likelihood that the observed therapeutic benefits are a chance occurrence
      resulting from uncorrected multiple subgroup comparisons. It remains uncertain
      whether elective lymphadenectomy can be therapeutically beneficial in the
      management of melanoma. Nevertheless, it is clear that the procedure, or
      preferably sentinel lymphatic mapping with selective lymphadenectomy, can provide
      clinically relevant prognostic information, as well as the staging data requisite
      to adjuvant interferon alfa-2b therapy or enrollment into other adjunctive trials
      for patients at high risk of clinical relapse.

PMID- 9267248
TI  - The pathogenesis of chronic idiopathic urticaria.
AB  - Chronic idiopathic urticaria (CIU) can be extremely disabling and difficult to
      treat, with little response to antihistamine therapy. The pathogenic mechanisms
      of the disease are not well understood, but the primary effector cell is the mast
      cell. Release of mast cell mediators can cause inflammation and accumulation and
      activation of other cells, including eosinophils, neutrophils, and possibly
      basophils. Recent work has demonstrated that about one third of patients with CIU
      have circulating functional histamine-releasing autoantibodies that bind to the
      high-affinity IgE receptor (Fc epsilon RI) or, less commonly, to IgE; mast cell
      specific histamine-releasing activity that has not yet been fully characterized;
      no identifiable circulating histamine-releasing activity. The mainstay of
      treatment of CIU consists of antithistamines, but immunotherapy using
      plasmapheresis, intravenous immunoglobulin, and cyclosporin may be valuable in
      severely affected patients with treatment-resistant disease. The response to
      immunomodulation and the recent finding of an association with HLA DR4 lend
      further support for an autoimmune basis to CIU in some patients.

PMID- 9267249
TI  - Sentinel lymph node evaluation in melanoma.
AB  - The surgical treatment of patients with cutaneous melanoma has been
      revolutionized by the development of lymphatic mapping and sentinel lymph node
      biopsy. This procedure involves injecting a radioactive tracer at the site of the
      primary melanoma (before wide excision); the tracer then travels via the
      lymphatics to the first draining or sentinel lymph node. The node is removed and
      evaluated for the presence of metastatic melanoma. In this way, patients who are
      most likely to benefit can be selected for regional lymphadenectomy. In addition,
      accurate and minimally invasive staging allows the surgeon to identify patients
      who may benefit from adjuvant and investigational immunotherapy. We review the
      development of lymphatic mapping, the technical details related to the procedure
      itself, and the published clinical studies using this new procedure. In addition,
      we discuss the controversial issues that have been raised with the introduction
      of sentinel lymph node biopsy.

PMID- 9267250
TI  - Papular and nodular lesions of the scalp, face, and neck. Secondary syphilis.

PMID- 9267251
TI  - Generalized ulcers. Noduloulcerative syphilis (malignant syphilis, lues maligna).

PMID- 9267252
TI  - Asymptomatic macular erythematous lesions. Lepromatous leprosy, macular stage.

PMID- 9267253
TI  - Purple erythematous plaques on the face and left arm. Chromomycosis.

PMID- 9267254
TI  - Interobserver variability in dermatopathology.

PMID- 9267255
TI  - Molluscum contagiosum. New insights, new directions.

PMID- 9267256
TI  - Development of melanocytic nevi in children.

PMID- 9267257
TI  - Do anti-basement membrane zone antibodies cause some cases of 'senile pruritus'?

PMID- 9267258
TI  - Role of human herpesvirus 8 in Kaposi sarcoma unclear.

PMID- 9267259
TI  - Thrombotic Klinefelter syndrome associated with factor V Leiden mutation.

PMID- 9267260
TI  - Oral lichen planus and hepatitis C virus infection: a fortuitous association?

PMID- 9267261
TI  - Systemic contact dermatitis caused by systemic corticosteroid use.

PMID- 9267263
TI  - Histologic correlation of image-guided core biopsy with excisional biopsy of
      nonpalpable breast lesions.
AB  - OBJECTIVE: To examine the histologic correlation between image-guided large-core
      needle biopsy (LCNB) and excisional biopsy of nonpalpable breast lesions. DESIGN:
      Histologic findings of LCNB and excision specimens were reviewed for patients who
      underwent image-guided LCNB of nonpalpable breast lesions from April 1, 1993, to
      March 31, 1996. Histologic diagnosis of the excision specimen was used as a
      criterion standard. Follow-up ranged from 1 to 4 years. SETTINGS: A dedicated
      breast imaging clinic on the campus of an urban community hospital. PATIENTS:
      Five hundred fifty-two patients with nonpalpable mammographically detected
      abnormalities. MAIN OUTCOME MEASURES: Histologic diagnoses of LCNB and excision
      specimens (part of a prospectively designed, ongoing quality audit process).
      RESULTS: Histologic findings were benign in 389 LCNB specimens (70.5%) and
      abnormal in 163 (29.5%). The benign LCNB specimens remained benign on clinical
      and radiologic follow-up, with 1 missed malignant diagnosis. One hundred seventy
      three patients underwent excision following LCNB, resulting in 10 benign and 163
      abnormal specimens. Diagnoses of 102 LCNB specimens showing invasive cancer were
      confirmed on excision. Of 54 patients in whom LCNB specimens showed ductal
      carcinoma in situ (DCIS), 10 showed DCIS plus invasive cancer on excision. Of 6
      patients in whom LCNB specimens showed atypical duct hyperplasia (ADH), 1 was
      benign, 1 showed ADH and invasive cancer, 3 showed ADH and DCIS, and 1 remained
      ADH exclusively on excision. The histologic diagnosis for 10 benign LCNBs
      remained benign after excision. Correlation coefficient was 0.93 (P < .001).
      CONCLUSIONS: Benign disease and invasive cancer of the breast can be diagnosed
      with a high level of confidence using image-guided LCNB. The histologic diagnosis
      for patients whose LCNB specimens show ADH or DCIS may change after excision.

PMID- 9267262
TI  - The place of trust in our changing surgical environment.

PMID- 9267264
TI  - Is pediatric laparoscopic splenectomy safe and cost-effective?
AB  - OBJECTIVE: To determine whether laparoscopic splenectomy (LS) is a safe, cost
      effective alternative to open splenectomy (OS). DESIGN: Retrospective comparison
      and economic evaluation. SETTING: Tertiary care children's hospital. PATIENTS:
      Children with hematologic disease involving the spleen. INTERVENTIONS:
      Laparoscopic splenectomy (10 patients); OS (10 patients). MAIN OUTCOME MEASURES:
      Safety of LS and cost differential between LS and OS. RESULTS: Operative time was
      longer for LS. Discharge occurred 64 hours postoperatively for LS and 79 hours
      for OS (P < .03). Patients who underwent LS returned to activity 1 to 5 weeks
      faster than patients who underwent OS. The average (+/-SD) operative charges for
      LS was $7176 +/- $2064 and for OS, $1977 +/- $344 (P < .001). Total hospital
      charges averaged $13,033 +/- $2976 for LS and $7106 +/- $1923 for OS (P < .001).
      CONCLUSIONS: Laparoscopic splenectomy can be performed safely in children. In our
      hospital, LS is more expensive than OS. The faster return to school and normal
      activity warrants the continued use of this procedure despite the increased cost.

PMID- 9267265
TI  - Biofeedback is effective therapy for fecal incontinence and constipation.
AB  - OBJECTIVE: To define the role of biofeedback in fecal incontinence and
      constipation. DESIGN: A case series of patients with fecal incontinence or
      constipation with pelvic floor dysfunction. SETTING: Tertiary care center with an
      anorectal physiology laboratory. PATIENTS: Patients with 1 of the following: (1)
      chronic or acute fecal incontinence, (2) fecal incontinence and neurologic
      injury, or (3) constipation with pelvic floor dysfunction. INTERVENTION:
      Electromyogram-guided biofeedback retraining of the pelvic floor. MAIN OUTCOME
      MEASURES: Resolution of electromyographic abnormalities and subjective resolution
      of fecal incontinence or constipation. RESULTS: Of the patients with fecal
      incontinence, 92% experienced significant improvement with biofeedback without
      significant improvement in electromyographic values. Of the patients with
      constipation and pelvic floor dysfunction 80% experienced improvement with
      biofeedback without significant change in electromyographic values. CONCLUSION:
      Biofeedback is effective in selected patients with fecal incontinence and
      constipation with pelvic floor dysfunction.

PMID- 9267266
TI  - Ability of ankle-brachial index to detect lower-extremity atherosclerotic disease
      progression.
AB  - BACKGROUND: Accurate determination of progression of lower-extremity arterial
      occlusive disease (LEAOD) is required for natural history studies and evaluation
      of therapies for atherosclerosis. OBJECTIVE: To determine if changes in the ankle
      brachial index (ABI) correlated with progression of LEAOD as determined by
      arteriography or duplex scanning. DESIGN: In patients with prior suprainguinal or
      infrainguinal lower-extremity revascularization, progression of LEAOD in native
      arteries was determined by comparing a preoperative (baseline) arteriogram with
      late follow-up arteriography or duplex scanning. Superficial femoral and
      popliteal arteries were graded as having less than 50% stenosis, 50% to 99%
      stenosis, or as being occluded. Tibial arteries were graded as continuously
      patent or occluded. Operated and nonoperated extremities were included in the
      study. The baseline ABI was performed postoperatively and repeated at follow-up
      arteriography or duplex scanning. Progression of LEAOD by the ABI was defined as
      a decrease in the ABI of 0.15 or greater. Progression of LEAOD by imaging studies
      was defined as an increase in 1 category of stenosis. Extremities with
      suprasystolic pressures were excluded. SETTING: Tertiary vascular surgical
      service. EXTREMITIES AND PATIENTS: One hundred ninety-three extremities were
      studied in 114 patients during a mean follow-up of 3.3 years. RESULTS: Seventy
      two lower extremities (37.3%) showed progression of atherosclerosis by late
      follow-up arteriography or duplex scanning. Using the imaging studies as the
      criterion standard, the ABI had 102 true negatives, 29 true positives, 42 false
      negatives, and 20 false positives (sensitivity, 41%; specificity, 84%; positive
      predictive value, 59%; negative predictive value, 71%; and accuracy, 68%) for
      determining the progression of LEAOD. CONCLUSIONS: The ABI is relatively
      insensitive in identifying the progression of LEAOD as demonstrated by the use of
      imaging studies. In studies of natural history or therapy for atherosclerosis,
      imaging studies should be used in preference to the ABI to evaluate the
      progression of LEAOD accurately.

PMID- 9267267
TI  - Superior outcomes in pediatric renal transplantation.
AB  - BACKGROUND: Nationally, results of renal transplantation in children,
      particularly in small children, are inferior to those obtained in adults.
      OBJECTIVE: To determine factors important for success in renal transplantation in
      children. DESIGN: Results of 108 consecutive renal transplantations performed in
      patients aged 7 months to 18 years were reviewed and compared with those reported
      by the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS), the
      national registry. RESULTS: One-, 2-, and 3-year graft survival rates (+/-SE)
      were 99% +/- 1%, 95% +/- 3%, and 93% +/- 4%, respectively, for living donor
      grafts and 97% +/- 3%, 92% +/- 6%, and 92% +/- 6%, respectively, for cadaver
      grafts. Incidence of acute rejection was half that reported by NAPRTCS. There
      were no graft losses for technical reasons (19% in NAPRTCS). Twelve percent of
      patients were younger than 2 years (6% in NAPRTCS); 17% were 2 to 5 years old
      (16% in NAPRTCS). Most small children received an adult-sized kidney. Ninety
      three percent of recipients weighing 15 kg or less received postoperative
      mechanical ventilation assistance to optimize fluid resuscitation and perfusion
      of adult-sized kidneys. Structural abnormalities of the urinary tract were
      present in 53.7% of the patients (48.5% in NAPRTCS; adults, 5.3%).
      Nephroureterectomy was required in 38 children; in 27 (71%) of them, it was
      performed at the time of transplant surgery. CONCLUSIONS: Excellent results can
      be obtained in pediatric renal transplantation by strict adherence to surgical
      detail, tight immunosuppressive management, aggressive fluid management in the
      small child, and careful integration of urologic and transplant surgery.

PMID- 9267268
TI  - Tracheobronchial resection and reconstruction.
AB  - OBJECTIVE: To assess the indications and results of airway resection and how
      frequently airway reconstructive options changed proposed therapy. DESIGN: A
      retrospective survey of patients undergoing major airway resection. SETTING:
      University of Washington-affiliated hospitals, Seattle, May 1992 through December
      1996. PATIENTS: Fifty consecutive patients with resectable benign and malignant
      tracheal or main bronchial disease undergoing tracheobronchial resections.
      INTERVENTIONS: Patients underwent major airway resection as follows: tracheal or
      laryngotracheal resection, 23 patients; carinal resection, 6; and bronchial
      sleeve resection with or without pulmonary resection, 21. Indications for surgery
      were non-small cell lung cancer in 19 patients, primary airway tumor in 12,
      thyroid carcinoma in 1, and tracheal or bronchial stenosis in 18. MAIN OUTCOME
      MEASURES: Change in prereferral planned therapy from palliative to definitive or
      to pulmonary-sparing procedure, morbidity and mortality, relief of symptoms, and
      survival. RESULTS: Mortality was 0%, and morbidity, 32% (15/50). Airway
      reconstruction changed the proposed therapy in 42 patients (84%). Functional
      results were good to excellent in 17 (94%) of 18 patients with benign disease.
      Patients with malignant disease had a 1-year survival of 93% (27/29) and a 2-year
      survival of 67% (12/18). CONCLUSIONS: Airway resection and reconstruction provide
      reliable relief of benign and malignant tracheobronchial disease with minimal
      morbidity and mortality. Airway reconstruction frequently changed prereferral
      planned therapy and provided definitive and parenchymal-sparing procedures to
      patients with complex airway lesions.

PMID- 9267269
TI  - Reduction in costs, blood products, and operating time in patients undergoing
      open heart surgery.
AB  - OBJECTIVE: To test the hypothesis that use of aprotinin at hall dose would be
      more cost-effective or as efficacious as full-dose aprotinin or no aprotinin
      during open heart surgery. DESIGN: Cost-effective analysis, unmasked prospective
      comparison. SETTING: Community hospital. PATIENTS: One hundred thirty-three
      patients undergoing open heart surgery. INTERVENTIONS: Patients in 3 consecutive
      groups undergoing open heart surgery were allocated to receive no aprotinin, full
      dose aprotinin, or half-dose aprotinin. MAIN OUTCOME MEASURES: Total cost (in
      dollars) of blood products administered plus cost of aprotinin at various
      dosages, comparison of total blood products administered during hospitalization,
      and closure time required in the operating room. RESULTS: Full-dose and half-dose
      aprotinin significantly (P < .05) reduced the total blood products administered
      during hospitalization and the operating room closure time. However, use of half
      dose aprotinin resulted in a significant cost savings (P < .05) when compared
      with either the cost of blood products required in the nodose aprotinin group or
      the cost of blood products plus aprotinin in the full-dose aprotinin group.
      CONCLUSION: Use of aprotinin at half dose in a community hospital resulted in a
      significant reduction in costs, blood product use, and operating room closure
      time in patients undergoing open heart surgery.

PMID- 9267270
TI  - Timing of the occurrence of pulmonary embolism in trauma patients.
AB  - OBJECTIVE: To determine how soon after trauma pulmonary embolism (PE) occurs and
      if there is an association between the duration of this interval and mortality.
      DESIGN: Retrospective case series. PATIENTS: All patients admitted to our trauma
      service with established PE based on high probability findings on ventilation
      perfusion scan, positive results on a pulmonary arteriogram, or autopsy from July
      1, 1990, to September 30, 1995. MAIN OUTCOME MEASURE: Time interval between
      injury and PE. SETTING: Level I university trauma center. RESULTS: Of 18,255
      trauma patients identified, 63 met our criteria for PE (30 using a pulmonary
      arteriogram; 26, a ventilation perfusion scan; and 7, autopsy). Four patients
      (6%) had a documented PE on day 1 following injury. Mortality was not correlated
      with the interval between injury and PE. Of the 63 patients, 58 (92%) had 1 or
      more established risk factors for thromboembolism. The ratio of PaO2 to fraction
      of inspired oxygen was the only factor predictive of mortality (P = .02, logistic
      regression analysis). CONCLUSIONS: Pulmonary embolism occurs in the immediate
      period following injury. Aggressive workup in patients with signs consistent with
      PE should be instituted promptly. Trauma patients who have at least 1 risk factor
      for thromboembolism should receive prophylaxis as soon after injury as possible.

PMID- 9267271
TI  - Flap selection as a determinant of success in pressure sore coverage.
AB  - OBJECTIVE: To establish a treatment algorithm for the long-term surgical
      management of pressure sores. DESIGN: Retrospective case series. SETTING:
      University-based teaching hospital. PATIENTS: From March 1979 to July 1995, 280
      unselected pressure sore reconstructions (113 ischial, 94 sacral, and 73
      trochanteric sores) were performed in 201 patients (130 men and 71 women; age
      range, 16-90 years; mean, 50 years). Of the patients, 90% had severe spinal cord
      injuries (paraplegia or quadriplegia). Forty-one percent of the wounds were
      chronic (present longer than 3 months). MAIN OUTCOME MEASURES: Length of stay,
      postoperative morbidity and mortality, and flap success (defined as a completely
      healed wound). RESULTS: Overall, 89% of the flaps healed primarily (ischium, 83%
      [94/113]; sacrum, 91% [86/94]; trochanter, 93% [68/73]). Three fourths of cases
      were treated in a single stage (debridement and reconstruction). The inferior
      gluteus maximus island flap (ischium) (94% [32/ 34]), the V-Y gluteus maximus
      advancement flap (sacrum) (97% [36/37]), and the tensor fascia lata flap
      (trochanter) (95% [42/44]) had the highest success rates. Flap success was not
      significantly affected by the size of the pressure sore or the number of previous
      flaps used. Postoperative hospital stays averaged 20 days. The overall
      complication rate was 28%, most commonly from a slight wound edge dehiscence.
      CONCLUSIONS: Flap selection and the appropriate short- and long-term sequence of
      flap use significantly improve success rates for pressure sore coverage.
      Reconstruction can be reliably performed in a single stage with a relatively
      short hospitalization.

PMID- 9267272
TI  - Preemptive analgesia in patients undergoing appendectomy.
AB  - OBJECTIVE: To evaluate the use of preemptive analgesia in patients who were
      undergoing an operation for acute appendicitis. DESIGN: Double-blind, randomized
      control trial. SETTING: Public hospital. PATIENTS: Patients who presented with
      presumed appendicitis. INTERVENTION: Patients received 1 of the following
      treatments: group 1, preemptive analgesia with a combination of lidocaine
      hydrochloride and bupivacaine hydrochloride; group 2, preemptive analgesia with
      saline solution; or group 3, nothing. MAIN OUTCOME MEASURES: The Wong-Baker FACES
      Pain Rating Scale, analgesic requirements, number of analgesic doses required,
      and length of hospital stay. RESULTS: No differences were noted in postoperative
      pain, the total number of analgesic doses per day, the quantity of narcotic
      medication administered, and the length of hospital stay. CONCLUSIONS: Compared
      with healthy control subjects, preemptive analgesia did not reduce postoperative
      pain, reduce analgesic requirements, or shorten the length of hospital stay in
      patients who underwent an appendectomy. Premptive analgesia may be applicable
      only for patients without preoperative pain.

PMID- 9267273
TI  - Morbid prognostic features in patients with chronic liver failure undergoing
      nonhepatic surgery.
AB  - BACKGROUND: Although the risk of portal decompression surgery is accurately
      predicted by objective scoring systems (Child classification and Pugh score), few
      useful prognostic criteria exist regarding nonhepatic surgery in patients with
      chronic liver failure. OBJECTIVE: To evaluate the clinical findings associated
      with perioperative mortality in patients with chronic liver failure undergoing
      nonhepatic surgery. DESIGN: A retrospective cohort study. SETTING: University
      teaching hospitals. PATIENTS: Forty consecutive patients with an International
      Classification of Diseases, Ninth Revision (ICD-9), diagnosis of chronic liver
      failure and one or more of the following: jaundice, cirrhosis, chronic hepatitis,
      or alcoholism. INTERVENTIONS: Forty operations, including 28 abdominal
      procedures, 2 coronary artery bypass grafts, 5 orthopedic procedures, and 5
      miscellaneous procedures. MAIN OUTCOME MEASURES: Thirty-day mortality as related
      to 19 preoperative clinical and laboratory variables. RESULTS: Eleven (28%) of
      the patients died within 30 days of surgery. By univariate analysis, the
      following variables were significantly (P < .05, pearson chi 2 test for
      categorical data or Mann-Whitney U test for continuous data) associated with
      nonsurvival: encephalopathy, congestive heart failure, the need for emergent
      surgery, infection, hyperbilirubinemia, international normalized ratio greater
      than 1.6, hypoalbuminemia, and an elevated creatinine level. By multiple logistic
      regression analysis, an international normalized ratio greater than 1.6 and
      encephalopathy were associated with a greater than 10- and 35-fold increased
      mortality risk, respectively. Child classification and Pugh score failed to
      predict 30-day mortality. CONCLUSIONS: We identified 8 clinical and laboratory
      variables associated with death within 30 days in patients with chronic liver
      failure undergoing nonhepatic surgery. Two factors-international normalized ratio
      greater than 1.6 and encephalopathy-independently predicted mortality by
      multivariate analysis. Neither Child classification nor Pugh score was
      prognostically helpful. Nonhepatic surgery confers a substantial mortality risk
      in patients with chronic liver failure.

PMID- 9267274
TI  - Efficacy of selective unilateral exploration in hyperparathyroidism based on
      localization tests.
AB  - OBJECTIVES: To determine the success of unilateral exploration vs bilateral
      exploration for primary hyperparathyroidism and to analyze the validity of
      preoperative localization tests. DESIGN: Case-control study of patients who
      underwent surgical exploration (unilateral, n = 43; bilateral, n = 57) by 1
      surgeon from January 1991 through May 1996 and who had ultrasound examination of
      the neck and thallium-technetium scintigraphy performed before parathyroid
      surgery. Initially, unilateral exploration was used sparingly, but it became the
      standard approach in 1994 if localization was correct. SETTING: Urban
      multispecialty clinic, teaching hospital. PATIENTS: One hundred consecutive
      patients who underwent surgical exploration for primary hyperparathyroidism.
      INTERVENTIONS: Ultrasonography of the neck, thallium-technetium scintigraphy, and
      parathyroidectomy. MAIN OUTCOME MEASURES: Imaging success, operative success, and
      operative time. RESULTS: In 94 patients with solitary adenomas, the adenoma was
      demonstrated by ultrasound scans in 66%, by thallium-technetium scintigraphy in
      83%, and by either test in 87%. Correct identification by ultrasonography was
      59%; by thallium-technetium scintigraphy, 75%; and together, 73%. Of 6 patients
      with multiple-gland disease, 2 were correctly identified by localization tests
      and 9 of 15 abnormal glands were demonstrated. Of the 43 unilateral explorations,
      43 single adenomas and no cases of multiple-gland disease were identified; of the
      57 bilateral explorations, 51 single adenomas and 6 cases of multiple-gland
      disease were identified. No complications occurred in either group. Hypercalcemia
      persisted in 3 patients who underwent bilateral exploration and recurrent
      hypercalcemia developed in 1 patient in each group. The average operative time
      for the unilateral procedure was 105 minutes, and for the bilateral procedure,
      184 minutes (P < .001). Since 1994, 31 (66%) of 47 patients have had unilateral
      exploration based on correct localization tests. CONCLUSIONS: Unilateral
      exploration that is based on the results of localization tests requires less
      operative time and produces results similar to bilateral exploration.

PMID- 9267275
TI  - The European Board of Surgery Qualification.

PMID- 9267276
TI  - Staphylococcus epidermidis graft infection is associated with locally suppressed
      major histocompatibility complex class II and elevated MAC-1 expression.
AB  - OBJECTIVES: To determine the local cellular immune response in a series of human
      patients with Staphylococcus epidermidis prosthetic graft infection and to use a
      murine model to investigate the response in polytef (PTFE) and in a nonslime
      producing S epidermidis variant. METHODS: Externally supported Dacron and PTFE
      grafts, either sterile or colonized with slime (RP-62A)- or nonslime (RP-62NA)
      producing S epidermidis (10(7) colony forming units/cm2) were implanted in a
      dorsal subcutaneous pocket of Swiss Webster mice (Taconic, Germantown, NY). The
      grafts were harvested at 7, 10, 14, and 28 days with local bacterial and
      leukocyte counts obtained. Perigraft and blood monocyte major histocompatibility
      complex class II (MHC-II) (immune antigen) and membrane attack complex type 1
      (MAC-1) (glycoprotein) expression were analyzed by flow cytometry in the murine
      model and in 3 patients representing 4 Dacron graft infections. RESULTS: The
      human infected Dacron perigraft monocytes revealed a suppressed MHC-II and
      elevated MAC-1 expression, and early correlation with the murine model was seen.
      No notable perigraft monocyte MHC-II suppression occurred in the infected PTFE
      graft. The reciprocal relationship in Dacron between monocyte MAC-1 and MHC-II
      expression was exaggerated with the lack of slime production. Bacterial clearance
      was variable. Supranormal expression was observed at 1 month in sterile Dacron
      but not in PTFE grafts. CONCLUSIONS: Staphylococcus epidermidis infection is
      associated with local cellular immune suppression in Dacron but not PTFE grafts.
      Slime-producing S epidermidis induced a lesser cytotoxic-phagocytic response than
      the nonslime variant. The reduced immunologic response to slime-producing S
      epidermidis may explain, in part, its indolent nature and resistance to
      eradication.

PMID- 9267277
TI  - Frequency and duration of remission after isolated limb perfusion for melanoma.
AB  - OBJECTIVE: To examine the frequency and duration of complete remission for
      locally recurrent and metastatic limb melanoma after isolated limb perfusion
      (ILP) with cytotoxic agents. DESIGN: A case series of 114 consecutive therapeutic
      ILPs performed between April 1984 and April 1994 and a review of previously
      published studies. SETTING: A tertiary referral center for melanoma treatment,
      located at a university teaching hospital. RESULTS: Of 111 assessable ILPs, 81
      (73%) resulted in complete limb tumor remission and 14 (13%) resulted in partial
      remission (defined as a reduction in size of tumor deposits by > 50%). Complete
      remission was maintained in 37 (46%) of the 81 cases without any further
      treatment (median follow-up, 33 months; range, 8-112 months). Of the other 44
      cases, disease subsequently recurred in the perfused limb (median time to
      recurrence, 9.5 months; range, 2-65 months). In 19 of these cases, however, the
      limb was again disease free at last follow-up after local surgery (12 cases) or a
      repeat ILP (7 cases). Overall, complete locoregional control was achieved after
      50% of assessable ILPs, and a long-term disease-free state in the limb was
      achieved, with or without further treatment, in 56 (69%) of the 81 cases in which
      an initial complete remission occurred. For 743 therapeutic ILPs undertaken in 12
      series previously reported in the literature, an initial complete remission was
      reported in 50% of these cases and partial remission in 32%. CONCLUSION:
      Therapeutic ILP is an effective form of treatment for patients with recurrent and
      metastatic limb melanoma, achieving short- and long-term results that are
      superior to those achievable by any other form of treatment currently used.

PMID- 9267278
TI  - Evaluation of diagnostic peritoneal lavage in stable patients with gunshot wounds
      to the abdomen.
AB  - BACKGROUND: Diagnostic peritoneal lavage (DPL) is used to diagnose intra
      abdominal injury in patients with stab wounds and blunt trauma. Because
      exploratory celiotomy is routinely performed on patients with gunshot wounds to
      the abdomen, DPL is rarely employed. However, several studies have questioned
      routine exploration and have drawn attention to the associated morbidity of
      negative celiotomy. Diagnostic peritoneal lavage is an easily performed and
      inexpensive test that may be useful in this situation. OBJECTIVE: To evaluate the
      performance of DPL in the diagnosis of intra-abdominal injury in hemodynamically
      stable patients with gunshot wounds to the abdomen. DESIGN: A prospective
      clinical trial. SETTING: Two urban trauma centers. PATIENTS: Patients with
      gunshot wounds to the abdomen and a systolic blood pressure of at least 90 mm Hg.
      INTERVENTIONS: Clinical predication of intra-abdominal injury in the emergency
      department and DPL performed in the operating room before the initiation of
      celiotomy. Injuries found during the celiotomy were recorded. MAIN OUTCOME
      MEASURES: The results of the clinical evaluation and DPL were compared with the
      findings of the celiotomy. RESULTS: Forty-four patients were enrolled into the
      study. Intra-abdominal injury was present in 32 (73%) of these patients. The
      senior surgery resident correctly predicted the presence of intra-abdominal
      injury in 36 (82%) of the patients (sensitivity = 90.0%, specificity = 58.3%,
      positive predictive value = 85.3%, negative predictive value = 63.6%, phi = 0.52,
      P < .01) in the emergency department before DPL and celiotomy were performed.
      Diagnostic peritoneal lavage correctly identified the presence or absence of
      intra-abdominal injury in 40 (91%) of the patients (positive predictive value =
      96.7%, negative predictive value = 78.6%, phi = 0.79, P < .01). CONCLUSIONS:
      Clinical judgment is highly accurate in separating patients with tangential
      gunshot wounds to the abdomen from those with intra-abdominal injury but may miss
      patients with intra-abdominal hemorrhage. Diagnostic peritoneal lavage is highly
      predictive of the presence of intra-abdominal injury. The return of gross blood
      on aspiration or a lavage red blood cell count greater than 10 x 10(9)/L should
      prompt an urgent celiotomy. Missed injuries are rare and most likely to be bowel
      perforations. Diagnostic peritoneal lavage is an objective test that may augment
      clinical judgment in selecting hemodynamically stable patients with potential
      tangential gunshot wounds for observation and is especially useful in identifying
      intra-abdominal hemorrhage.

PMID- 9267279
TI  - Prevalence of adrenal carcinoma among incidentally discovered adrenal masses. A
      retrospective study from 1989 to 1994. Gruppo Piemontese Incidentalomi
      Surrenalici.
AB  - BACKGROUND: The incidental discovery of an adrenal mass poses the problem of
      distinguishing between the frequent benign masses and the infrequent malignant
      ones that require surgery. Univocal guidelines to approach this problem are
      unavailable. OBJECTIVE: To perform a survey of the clinical management of
      incidentally discovered adrenal masses (ie, adrenal incidentalomas). DESIGN: A
      multicentric retrospective analysis of hospital medical records of adrenal
      incidentalomas diagnosed during a 5-year period; the medical records were
      scrutinized for demographic data and clinical details by means of a specifically
      tailored questionnaire. SETTING: The major surgical and medical centers of
      Piedmont, a northern Italian region with approximately 4 million inhabitants. The
      recruitment pattern of these centers was unselected. PATIENTS: The definition of
      adrenal incidentaloma was limited to patients with a physical examination and a
      clinical history unindicative of adrenal disease. Exclusion criteria also
      included hypertension of suspected endocrine origin and a history of neoplasms
      known to metastasize frequently in the adrenal glands. Two hundred twenty-four
      medical records were collected, and 210 were analyzed (14 excluded a posteriori).
      RESULTS: Most patients were in their 50s and 60s, and women were predominantly
      affected. The frequency of adrenocortical cancer was 13% among patients operated
      on. The tumor diameter was highly correlated with the risk of cancer; a cutoff at
      5 cm had a sensitivity of 93% with a specificity of 64% in discriminating between
      benign and malignant cortical lesions. CONCLUSIONS: The occurrence of
      adrenocortical carcinoma among adrenal incidentalomas is not rare. The evaluation
      of the mass size is a simple and effective method for selecting patients at risk
      for cancer. The indication for surgery of masses larger than 5 cm, or of masses
      of any diameter that have suspicious imaging characteristics, limits unnecessary
      operations and costs.

PMID- 9267280
TI  - The complications of trauma and their associated costs in a level I trauma
      center.
AB  - OBJECTIVES: To estimate the expected costs for acute trauma care, to quantify the
      costs associated with the development of complications in injury victims, and to
      determine the deficit incurred by patients in whom complications develop. DESIGN:
      A retrospective, cohort design. SETTING: A referral trauma center. PATIENTS: A
      total of 12,088 patients admitted to a single regional trauma center during a
      period of 5 years. INTERVENTIONS: This is an observational study, and no
      interventions specific to this study are included in the design. MAIN OUTCOME
      MEASURES: (1) The expected costs for injury victims based on readily available
      clinical data. (2) The costs associated with the most important complications of
      trauma. (3) The effect of complications on inadequate reimbursement for trauma
      care. RESULTS: The expected costs were estimated using a linear model
      incorporating demographic variables and measures of injury severity. The expected
      costs averaged $14,567, and the observed costs averaged $15,032. Six
      complications were important predictors of cost. These included adult respiratory
      distress syndrome, acute kidney failure, sepsis, pneumonia, decubitus ulceration,
      and wound infections. For 1201 individuals with these complications, the
      predicted costs averaged $23,266 and the observed costs averaged $47,457. The
      mean excess costs for a single complication ranged from $6669 to $18,052.
      Multiple complications led to greater increases in excess cost, averaging
      $110,007 for the 62 patients with 3 or more complications. Costs exceeded
      reimbursement to a much greater degree in those in whom any of the 6
      complications developed. CONCLUSION: Expected hospital costs can be estimated
      using admission clinical data. Each of 6 complications was associated with
      enormous increases in costs, indicating their importance as a cause of avoidable
      expenditures in injury victims and identifying situations in which reimbursement
      may not be adequate.

PMID- 9267282
TI  - The learning curve for laparoscopic colorectal surgery.

PMID- 9267281
TI  - Pancreatic insulinomas. A 15-year experience.
AB  - OBJECTIVE: To describe our experience in the management of patients with
      pancreatic insulinomas, emphasizing the need for preoperative localization and
      the outcome of surgical treatment. DESIGN: A case series. SETTING: A university
      hospital in Hong Kong. PATIENTS: From 1981 to 1995, 27 patients with pancreatic
      insulinomas were surgically treated; the mean follow-up was 25.4 months. MAIN
      OUTCOME MEASURES: Postoperative morbidity and euglycemia during the follow-up
      period. RESULTS: The accuracy of tumor localization by ultrasonography, computed
      tomography, and angiography was 33%, 44%, and 52%, respectively. Venous sampling
      for an insulin assay regionalized 90% of the tumors. In 24 patients with solitary
      tumors, most lesions detected or missed by preoperative localization could be
      either seen (n = 14) or palpated (n = 22). Intraoperative ultrasonography (n =
      17) has been routinely performed since 1987; nonpalpable tumors were imaged in 2
      of 15 patients with solitary tumors. Eight solitary occult tumors were detected
      by palpation alone or a combination of palpation and intraoperative
      ultrasonography. Operative mortality occurred in 1 (3.7%) of the 27 patients,
      while major morbidity developed in 9 (33%) of the patients. Euglycemia was
      achieved in 25 patients. Surgery cured all patients with benign insulinomas,
      whereas the cure rate for patients with malignant neoplasms was only 33%. The
      type of surgical treatment or correct preoperative localization did not affect
      the outcome of surgery. CONCLUSIONS: Pancreatic insulinomas can be readily
      localized intraoperatively despite failed preoperative localization studies.
      Surgical treatment cured benign adenomas but was associated with notable
      morbidity.

PMID- 9267283
TI  - The learning curve for laparoscopic colorectal surgery.

PMID- 9267284
TI  - Moments in surgical history.

PMID- 9267286
TI  - Continuing transition in surgical care.

PMID- 9267285
TI  - Changing the delivery of surgical care.

PMID- 9267288
TI  - Leave no stone unturned.

PMID- 9267287
TI  - Inpatient today--outpatient tomorrow?

PMID- 9267289
TI  - Fixed hinge knee arthroplasty.

PMID- 9267291
TI  - Radiology for the surgeon. Case 16. Jejunogastric intussusception.

PMID- 9267290
TI  - Ultrasound diagnosis of acute appendicitis.

PMID- 9267292
TI  - The abdominal compartment syndrome.
AB  - The abdominal compartment syndrome refers to the alterations in respiratory
      mechanics, hemodynamic parameters and renal function that occur as a result of a
      sustained increase in intra-abdominal pressure. The syndrome may follow a diverse
      series of insults, including laparotomy for severe abdominal trauma, ruptured
      abdominal aortic aneurysm and intra-abdominal infection. Diagnosis depends on
      recognizing the clinical picture in patients at risk, followed by an objective
      measurement of intra-abdominal pressure. Successful management may require
      abdominal decompression with temporary abdominal closure. Despite urgent
      decompression, the death rate is high because of the severity of the patients'
      underlying illness.

PMID- 9267294
TI  - Long-term outcomes after upper limb arterial injuries.
AB  - OBJECTIVE: To assess long-term outcomes in multisystem trauma victims who have
      arterial injuries to upper limbs. DESIGN: A retrospective case series. SETTING:
      Tertiary care regional trauma centre in a university hospital. PATIENTS: All
      consecutive severely injured patients (Injury Severity Score greater than 15)
      with an upper limb arterial injury treated between January 1986 and January 1995.
      Demographic data and the nature and management of the arterial and associated
      injuries were determined from the trauma registry and the hospital records.
      OUTCOME MEASURES: Death rate, discharge disposition, residual disabilities and
      functional outcomes as measured by the Glasgow Outcome Scale. RESULTS: Twenty
      five (0.6%) of 4538 trauma patients assessed during the study period suffered
      upper extremity arterial injuries. Nineteen of them were victims of blunt trauma.
      The death rate was 24%. There were 10 primary and no secondary amputations. An
      autogenous vein interposition graft was placed in 10 patients. Concomitant
      fractures or nerve injuries in the upper limb were present in 80% and 86% of the
      patients, respectively. Long-term follow-up data (mean 2 years) were obtained in
      16 of the 19 who survived to hospital discharge. The residual disability rate was
      high. It included upper limb joint contractures, pain and persistent neural
      deficits (69%). Associated injuries in other body areas also contributed to
      overall disability. Only 21% of the patients recovered completely or had only
      minor disabilities. CONCLUSIONS: Associated injuries, rather than the vascular
      injury, cause long-term disability in the multisystem trauma victim who has upper
      extremity involvement. Persistent neural deficits, joint contractures and pain
      are the principal reasons for long-term impairment of function.

PMID- 9267293
TI  - Symposium on ambulatory surgery: principles, practice, pitfalls.

PMID- 9267295
TI  - An orthopedic surgeon survey on the treatment of displaced femoral neck fracture:
      opposing views.
AB  - OBJECTIVE: To examine the reasons for practice variation in the treatment of
      displaced femoral neck fractures. DESIGN: A survey, asking surgeons to choose
      either hemiarthroplasty or internal fixation for 2 different female patients with
      a displaced femoral neck fracture. SETTING: The Canadian Orthopaedic Association
      Meeting, Halifax, May 1995. PATIENTS: The scenario in the first patient was of an
      independent 70-year-old woman with no pre-existing medical conditions. The
      scenario in the second patient was of a housebound 84-year-old woman with co
      morbidity. MAIN OUTCOME MEASURES: Proportion of surgeons choosing either
      hemiarthroplasty or internal fixation for each case scenario. Distribution of
      reasons to explain the treatment decision. RESULTS: Ninety-nine surgeons
      responded. For the case of the 70-year-old woman, 47% chose hemiarthroplasty and
      53% chose internal fixation (p = 0.60), and for the 84-year-old woman, 96% chose
      hemiarthroplasty. These findings were consistent within the subgroups of teaching
      surgeons and community practice surgeons. Surgeons with 10 years or less of
      practice tended to favour hemiarthroplasty whereas those with more than 15 years'
      practice favoured internal fixation. Important reasons for treatment choice were
      avoidance of reoperation in the hemiarthroplasty group (85%) and better hip
      function in the fixation group (83%), durability (83%) and ease of revision
      (77%). CONCLUSION: The surgeon's interpretation of the importance of reoperation
      and function underlies the differences in treatment decision regarding the
      management of femoral neck fractures in elderly patients.

PMID- 9267296
TI  - Hinge total knee replacement revisited.
AB  - OBJECTIVE: To determine if aseptic loosening is a major problem in hinge total
      knee replacement. DESIGN: A cohort study. SETTING: A university-affiliated
      institute, specializing in elective orthopedic surgery. PATIENTS: Fifty-eight
      patients, mainly those requiring revision, in whom the conditions were such that
      it was felt only a totally constrained implant was appropriate. In 7 patients the
      implant was press-fitted; in the remainder it was cemented. Five patients
      required fusion or revision, and 8 died less than 2 years after implantation,
      leaving 45 for review. Follow-up was 2 to 13 years. INTERVENTION: Total knee
      replacement with a Guepar II prosthesis. MAIN OUTCOME MEASURES: Radiolucency
      determined by the Cameron system and clinical scoring using the Hospital for
      Special Surgery system. RESULTS: Of the cemented components, 91% of femoral stems
      were type IA (no lucency), 9% were type IB (partial lucency), with no type II or
      III lucency. Tibial lucency was 87% type IA and 13% type IB, with no type II or
      III lucency. Of the noncemented components, 58% of femoral components were type
      IA and 42% type IB. Tibial lucency was 71% type IA and 29% type IB. Lucency was
      mainly present in zones 1 and 2 adjacent to the knee. Clinical rating was 18%
      excellent, 20% good, 20% fair and 42% poor. Postoperative complications included
      infection (13%), aseptic loosening (7%), quadriceps lag (16%) and extensor
      mechanism problems (16%). CONCLUSIONS: Aseptic loosening is an uncommon problem
      in hinge total knee replacement. The complication rate in cases of sufficient
      severity as to require a hinge replacement remains high. Current indications for
      a hinge prosthesis are anteroposterior instability with a very large flexion gap,
      complete absence of the collateral ligaments and complete absence of a
      functioning extensor mechanism.

PMID- 9267297
TI  - Establishing outpatient cholecystectomy as a hospital routine.
AB  - OBJECTIVE: To determine the rate of outpatient cholecystectomies done voluntarily
      by surgeons and to identify any "correctable" factors leading to hospital
      admission, also to reassess the outpatient cholecystectomy rate after correcting
      the identified factors. DESIGN: A prospective analysis. SETTING: A 256-bed non
      teaching acute-care community hospital on the outskirts of a major urban centre,
      served by 4 general surgeons. PATIENTS: All 515 patients booked for elective
      cholecystectomy at the hospital between Apr. 1, 1994, and Mar. 31, 1996,
      inclusive. INTERVENTION: Elective outpatient cholecystectomy. MAIN OUTCOME
      MEASURE: A successful procedure without compromise of safety. RESULTS: In the
      preliminary study, outpatient cholecystectomy was done in 75% of the patients.
      Variations in individual surgical practice, preoperative patient selection and
      inappropriate day surgery facilities were thought to be correctable factors
      leading to admission. After correction of the these factors (follow-up study),
      the rate of outpatient cholecystectomy rose to 95% (p < 0.001). Variations in
      individual surgical practice disappeared, and no patient required processing
      through inappropriate day surgery facilities. No patient suffered untoward
      effects from outpatient management. CONCLUSIONS: Outpatient cholecystectomy is a
      safe hospital routine for all elective procedures without selection. Voluntary
      acceptance of this routine leads to an initial 75% outpatient rate. Identifying
      and correcting modifiable factors led to a significant increase in the
      institutional outpatient rate, comparable to reported individual rates.

PMID- 9267298
TI  - Duodenal seromyectomy in the management of adherent colonic carcinoma in elderly
      patients.
AB  - OBJECTIVE: To determine if partial denudation of the duodenum by seromyectomy can
      achieve tumour clearance in elderly patients with adherent primary colonic
      carcinoma. DESIGN: A case series. SETTING: An urban tertiary care centre.
      PATIENTS: Seven elderly patients with Dukes' class C primary adenocarcinoma of
      the ascending colon adherent to the duodenum but without distant metastases. The
      follow-up ranged from 29 to 41 months. INTERVENTIONS: Right hemicolectomy and
      seromyectomy of the duodenum at the site of adhesion. MAIN OUTCOME MEASURES:
      Patient survival and tumour recurrence. RESULTS: One patient died 29 months
      postoperatively of myocardial infarction but without tumour recurrence. Another
      patient had a solitary metastasis in the right liver lobe 7 months
      postoperatively. She was disease free 34 months after a right hemihepatectomy.
      The other 5 patients were alive and disease free at their last follow-up.
      CONCLUSION: Duodenal seromyectomy with postoperative chemotherapy for locally
      advanced adherent colonic cancer seems to be an acceptable management strategy
      for elderly patients in whom major en bloc resections present a greater than
      average risk of death.

PMID- 9267300
TI  - Don't cry over spilled stones? Complications of gallstones spilled during
      laparoscopic cholecystectomy: case report and literature review.
AB  - The gallbladder is perforated and stones are spilled more frequently during
      laparoscopic cholecystectomy than during open cholecystectomy. Recent reports
      have implicated spilled gallstones as a source of infrequent but serious
      complications of laparoscopic of laparoscopic cholecystectomy. They can cause
      serious morbidity, and in most cases the patient will require open surgery for
      management of these complications. The authors report the case of a patient who
      was ill for 14 months after laparoscopic cholecystectomy when spilled stones
      formed a nidus for intra-abdominal abscess and colocutaneous fistula. Every
      effort must be made to prevent gallbladder perforation. When it does occur, all
      stones should be retrieved. Attempts at repairing gallbladder perforations are
      often unsatisfactory. A simple solution to this potential problem is to retrieve
      all stones immediately, place them in an intraperitoneal specimen bag, and "park"
      the bag on the liver. As soon as the gallbladder is dissected off the liver it
      should be placed in the specimen bag with the stones and removed through the
      umbilical port opening.

PMID- 9267299
TI  - Clinical results of deep venous valvular repair for chronic venous insufficiency.
AB  - OBJECTIVE: To evaluate the results of venous valvular repair in the treatment of
      16 cases of chronic venous insufficiency (CVI). DESIGN: A retrospective analysis
      of 16 venous valve repair operations (15 patients) with a minimum follow-up of 2
      years. SETTING: A 650-bed university-affiliated teaching hospital. PATIENTS:
      Fifteen consecutive referred patients who had CVI had deep vein valve surgery.
      All cases were refractory to prolonged conservative care and removal of
      incompetent superficial and perforating veins. Investigation included ascending
      and descending venography, air plethysmography (APG) and colour flow duplex
      scanning (CFDS). All patients had class 4, 5 or 6 CVI and all demonstrated deep
      venous reflux from the groin to below the knee on descending venography.
      INTERVENTIONS: Superficial femoral vein valvuloplasty (12 operations) and venous
      valve transfer from the axillary vein to the above-knee popliteal vein (4
      operations). MAIN OUTCOME MEASURES: Healing of ulcers, relief of edema and
      improvement in symptoms were clinical criteria of success. An attempt was made to
      correlate preoperative and postoperative APG, CFDS and descending venography.
      RESULTS: Ninety-two percent of the valvuloplasty patients and 75% of the valve
      transfer patients were clinically improved. In this series no statistical
      association existed between preoperative and postoperative changes noted on APG.
      CONCLUSION: This series suggests that deep vein valvular reconstruction for CVI
      refractory to conservative management and superficial surgery offers a good
      chance of clinical improvement.

PMID- 9267301
TI  - Late presentation of an intra-abdominal foreign body.
AB  - Bowel obstruction by a foreign body is rare. The authors describe the case of a
      77-year-old woman who had small-bowel obstruction due to a foreign body 40 years
      after a transabdominal hysterectomy. A loop of small bowel had herniated through
      a metal ring and had become necrotic. The ring and involved bowel were excised
      and the patient's clinical course was uncomplicated. The original purpose of the
      ring remains a mystery. The time frame between the introduction of a foreign body
      and the occurrence of symptoms in this case appears to be the longest ever
      reported.

PMID- 9267302
TI  - Acute polyethylene fracture in an uncemented acetabular cup.
AB  - The smaller acetabular components used in total hip replacement may have a
      polyethylene liner that is too thin, resulting in higher polyethylene stress and
      an increased potential for wear. The authors present a case that highlights the
      problem of acute polyethylene fracture. To compensate for the thinness of the
      polyethylene, the authors recommend the use of a smaller head size to allow
      polyethylene thickness of at least 8 mm.

PMID- 9267303
TI  - Clenched-fist injury complicated by methicillin-resistant Staphylococcus aureus.
AB  - Hand infections are a common sequela of clenched-fist injuries. The majority of
      these infections are due to Staphylococcus and Streptococcus species. Methicillin
      resistant Staphylococcus aureus (MRSA) is increasingly being isolated in Canadian
      health care facilities. In addition, MRSA now needs to be considered in community
      acquired hand infections that fail to respond to common empiric therapy. A 51
      year-old man with MRSA due to a hand injury was treated successfully with
      vancomycin. The prevalence, mechanism of resistance and treatment of MRSA are
      briefly reviewed.

PMID- 9267304
TI  - The errors of our ways.

PMID- 9267305
TI  - Point: status of lipid and lipoprotein standardization.
AB  - Cholesterol and triglyceride standardization procedures have been used
      extensively and continuously since the 1950s. Definitive and Reference Methods,
      as well as primary and secondary standards, have been developed and maintained as
      the basis for evaluating the accuracy of results by various methods in many
      laboratories. But, although standardization efforts for apolipoprotein A-I and B
      measurements have been reported in detail in the scientific literature, much less
      has been reported in the area of total and lipoprotein cholesterol and
      triglyceride standardization efforts. Standardized cholesterol and triglyceride
      concentrations, determined in multiple large epidemiological and clinical
      studies, have been instrumental to the National Cholesterol Education Program
      panels that have assessed the lipoprotein values associated with risk of coronary
      disease, and have determined the cutpoints that are now used extensively by
      physicians to guide diagnosis and treatment of individual patients.

PMID- 9267306
TI  - Counterpoint: to (measure apo) B or not to (measure apo) B: a critique of modern
      medical decision-making.
AB  - The measurement of apo B provides critical information that is complementary to
      that provided by the plasma and lipoprotein lipids for the assessment of coronary
      risk and the choice of appropriate pharmacological therapy. Why then is this
      measurement not in more widespread clinical use? I suggest two explanations.
      First, against the evidence, there is a lingering perception that problems
      persist in its measurement in routine clinical practice. Far from this being the
      case, however, the measurement of apo B has met every reasonable standard of
      laboratory precision and reliability to allow its widespread introduction in
      clinical laboratories. The second impediment is that the introduction of new
      tests has become subject to the authority of consensus conferences, a new
      approach to medical decision-making. The number of such conferences is increasing
      astronomically, and their reports are major determinants of clinical practice and
      allocation of resources. Notwithstanding the benefits they have brought, here I
      argue that, just as with any other scientific method, the merits of this new
      method of decision-making need to be examined critically; for if we do not, a
      process that was established to introduce change may, in fact, retard it or
      destroy it altogether.

PMID- 9267307
TI  - Extraction of glyceric and glycolic acids from urine with tetrahydrofuran:
      utility in detection of primary hyperoxaluria.
AB  - Primary hyperoxaluria (PH) is an autosomal recessive metabolic abnormality
      characterized by excessive oxalate excretion leading to nephrocalcinosis and
      progressive renal dysfunction. Type I primary hyperoxaluria (PH I) results from a
      deficiency of alanine:glyoxylate aminotransferase, whereas type II disease has
      been traced to a deficiency of D-glycerate dehydrogenase. The two syndromes are
      often distinguished on the basis of organic acids that are coexcreted with
      oxalate: glycolate and L-glycerate in type I and type II disease, respectively.
      Routine organic acid analysis with diethyl ether extraction followed by gas
      chromatographic analysis failed to detect normal and increased concentrations of
      these diagnostic metabolites. Subsequent extraction of urine with tetrahydrofuran
      (THF), however, extracted 75% of added glycerate, 42% of added glycolate, and 75%
      of added ethylphosphonic acid (internal calibrator). THF extraction was
      analytically sensitive enough to allow determination of normal excretion of
      glycolate (14-72 micrograms/mg creatinine) and glycerate (0-5 years, 12-177
      micrograms/mg creatinine and > 5 years, 19-115 micrograms/mg creatinine). Four of
      five patients with PH I and both patients with type II disease were correctly
      identified. Thus, THF extraction is a convenient adjunct to routine organic acid
      analysis and facilitates the detection of PH.

PMID- 9267308
TI  - Apolipoprotein E genotyping by capillary electrophoretic analysis of restriction
      fragments.
AB  - We present the genotyping of apolipoprotein (apo) E by means of restriction
      fragment analysis of amplified genomic DNA by high-performance capillary
      electrophoresis and a replaceable non-gel-sieving matrix. This procedure
      streamlines the genotyping of apo E in large-scale population studies because of
      the automation and speed of capillary electrophoresis.

PMID- 9267309
TI  - Diagnosis of lysosomal storage disorders: evaluation of lysosome-associated
      membrane protein LAMP-1 as a diagnostic marker.
AB  - Early diagnosis of lysosomal storage disorders (LSDs), before the onset of
      irreversible pathologies, will be a key factor in the development of effective
      therapies for many of these disorders. Newborn screening offers a potential
      mechanism for the early detection of these disorders. From studies of both normal
      and LSD-affected human skin fibroblasts we identified the lysosome-associated
      membrane protein LAMP-1 as a potential diagnostic marker. We have developed a
      sensitive method for the quantification of this protein with a time-resolved
      fluorescence immunoassay. A soluble form of LAMP-1 was observed in plasma
      samples, and determination of 152 unaffected individuals gave a median value of
      303 micrograms/L with the 5th and 95th percentile at 175 and 448 micrograms/L
      respectively. Plasma samples from 320 LSD-affected individuals representing 25
      different disorders were assayed. We observed that 17 of the 25 disorder groups
      tested had > 88% of individuals above the 95th percentile of the control
      population, with 12 groups having 100% above the 95th percentile. Overall, 72% of
      patients had LAMP-1 concentrations above the 95th percentile of the unpartitioned
      control population. We suggest that LAMP-1 may be a useful marker in newborn
      screening for LSDs.

PMID- 9267310
TI  - A homogeneous method for genotyping with fluorescence polarization.
AB  - We combined the amplification refractory mutation system (ARMS) and fluorescence
      polarization (FP) to give a homogeneous genomic DNA genotype analysis method.
      Oligonucleotide probes labeled with the fluorescein dyes fluorescein
      isothiocyanate and 5-([4,6-dichlorotriazin-2-yl]amino)fluorescein and the
      rhodamine dye 6-carboxyrhodamine were included in amplification mixes and were
      annealed to PCR products after amplification. Hybridization was accompanied by an
      increase in the FP of the probe. We demonstrated homogeneous genotyping by
      analyzing human DNA samples for delta F508 mutation status of the cystic fibrosis
      transmembrane conductance regulator gene. The genotypes determined with the
      method described herein were in full agreement with those obtained by the
      conventional application of ARMS. We also demonstrated the simultaneous detection
      of two PCR products in a single reaction. The assay method described is
      homogeneous and so obviates the necessity to open reaction vessels after
      amplification. This therefore eliminates PCR carryover contamination.

PMID- 9267311
TI  - Creatinine measurement proficiency testing: assignment of matrix-adjusted ID GC
      MS target values.
AB  - The results of an external quality-assessment experiment for serum creatinine
      measurement are described. Fifty-one laboratories performed quintuplicate
      analyses during three different analytical runs on six lyophilized sera and two
      frozen human serum pools. Isotope dilution gas chromatography-mass spectrometry
      (ID GC-MS) target values were assigned to all the materials. Intralaboratory
      within- and between-run imprecision results were very similar for all the
      materials tested (CV < or = 2.20% and < or = 4.70%, respectively). The overall
      imprecision obtained was high (CV 6.5-20.0%) because of increased interlaboratory
      intermethod variability. A significant positive bias (+ 9.2-+43.7%) was found for
      all the materials at lower creatinine concentration. By using two human sera at
      different concentrations, we could calculate the constant and the proportional
      calibration bias displayed by each peer group. The majority of the lyophilized
      materials showed a behavior divergent from the frozen pools, indicating matrix
      related problems. We propose a new algorithm for calculating matrix bias
      correction factor instrument-reagent specific for each material.

PMID- 9267312
TI  - Mistakes in a stat laboratory: types and frequency.
AB  - Application of Total Quality Management concepts to laboratory testing requires
      that the total process, including preanalytical and postanalytical phases, be
      managed so as to reduce or, ideally, eliminate all defects within the process
      itself. Indeed a "mistake" can be defined as any defect during the entire testing
      process, from ordering tests to reporting results. We evaluated the frequency and
      types of mistakes found in the "stat" section of the Department of Laboratory
      Medicine of the University-Hospital of Padova by monitoring four different
      departments (internal medicine, nephrology, surgery, and intensive care unit) for
      3 months. Among a total of 40490 analyses, we identified 189 laboratory mistakes,
      a relative frequency of 0.47%. The distribution of mistakes was: preanalytical
      68.2%, analytical 13.3%, and postanalytical 18.5%. Most of the laboratory
      mistakes (74%) did not affect patients' outcome. However, in 37 patients (19%),
      laboratory mistakes were associated with further inappropriate investigations,
      thus resulting in an unjustifiable increase in costs. Moreover, in 12 patients
      (6.4%) laboratory mistakes were associated with inappropriate care or
      inappropriate modification of therapy. The promotion of quality control and
      continuous improvement of the total testing process, including pre- and
      postanalytical phases, seems to be a prerequisite for an effective laboratory
      service.

PMID- 9267313
TI  - Errors, mistakes, blunders, outliers, or unacceptable results: how many?
AB  - We have studied 219353 individual clinical chemistry results obtained in methods
      comparison studies. Each result was prospectively compared with its replicate,
      comparative, or repeat value to identify differences from expected values.
      Unacceptable results were defined as differing from the expected values by < or =
      7 SDs or CVs. We believe these differences represent special-cause variation and
      should be expressed as unacceptable rates per million results (ppm). We observed
      447 ppm unacceptables: 196 ppm in control samples and 251 ppm in patients'
      samples. Results judged likely to alter patient care occurred at a rate of 41
      ppm. To better understand the magnitude of these rates, we compared these results
      with reports of error rates in HIV testing and the airline industry. The
      measurements reported were made for the purpose of quality improvement, not
      judgment or discovery. The significance of these findings for laboratorians,
      manufacturers, and regulators is discussed.

PMID- 9267314
TI  - Increased alkaline phosphatase isoforms in autoimmune diseases.
AB  - We found significant increases in ALP and ALP isoform band 10 in the serum of
      patients with early insulin-dependent diabetes, rheumatoid arthritis, and in
      those with multiple sclerosis during periods of disease exacerbation as compared
      with healthy controls. The ALP isoforms were assayed by isoelectric focusing. Our
      data suggest that the increase in ALP and ALP-10 closely reflects the abnormal
      activation of T lymphocytes that is common in autoimmune diseases, and that the
      source of the ALP-10 is activated T lymphocytes. ALP-10 is a sensitive but
      nonspecific marker of an active autoimmune process and appears to have the
      ability to detect abnormal T-cell activation. ALP-10 may be a useful test in the
      screening for autoimmune disorders.

PMID- 9267315
TI  - Immunofluorometric assay of pepsinogen C and preliminary clinical applications.
AB  - We developed mouse monoclonal antibodies (Abs) against pepsinogen C with highly
      purified antigen isolated from gastric mucosa. The Abs were used to construct a
      two-site sandwich-type assay for pepsinogen C with time-resolved fluorometry as a
      detection technique. The assay has a detection limit of 0.1 microgram/L and is
      precise (within-run and day-to-day CVs < 11%). We used this assay to measure
      pepsinogen C in seminal plasma, breast cyst fluid, amniotic fluid, male and
      female serum, serum from patients with prostate cancer, urine, breast tumor
      cytosolic extracts, breast milk, and cerebrospinal fluid. Highest pepsinogen C
      concentrations were in seminal plasma, followed by breast cyst fluid and amniotic
      fluid. We found no correlation between prostate-specific antigen concentrations
      and concentrations of pepsinogen C in serum of prostate cancer patients, and
      concluded that this marker is not useful for either diagnosing or monitoring
      prostatic carcinoma. The availability of a highly sensitive, reliable, and
      convenient method for quantifying pepsinogen C will allow investigations into the
      possible diagnostic value of this analyte in various clinical conditions,
      including benign breast diseases, breast cancer, fertility, and pregnancy.

PMID- 9267316
TI  - Serum concentrations of myoglobin vs human heart-type cytoplasmic fatty acid
      binding protein in early detection of acute myocardial infarction.
AB  - We compared the diagnostic utility of serum concentrations of human heart-type
      cytoplasmic fatty acid-binding protein (H-FABPc), myoglobin, and their ratio for
      the early diagnosis of acute myocardial infarction (AMI) in 104 healthy
      volunteers and 165 patients at admission within 6 h of the onset of chest pain.
      The ROC curves of the H-FABPc [0.946, 95% confidence interval (CI) = 0.913-0.979]
      and myoglobin (0.895, 95% CI = 0.846-0.944) between patients with AMI and healthy
      volunteers were significantly greater than the area under the ratio of myoglobin
      to H-FABPc (0.823, 95% CI = 0.765-0.881). In 165 patients, the sensitivity
      (81.8%, 95% CI = 74.2-89.4%), specificity (86.4%, 95% CI = 78.1-94.6%), and
      predictive accuracy (83.6%, 95% CI = 78.0-89.3%) of H-FABPc > 12 micrograms/L in
      diagnosing AMI were significantly higher than those of myoglobin, and were
      similar to those of the combination of H-FABPc > 12 micrograms/L and the ratio <
      or = 14. We conclude that H-FABPc is a more sensitive and specific marker than
      myoglobin for the early diagnosis of AMI, and that their ratio cannot give a
      clear advantage over the measurement of H-FABPc alone.

PMID- 9267317
TI  - Troponin I is released in bloodstream of patients with acute myocardial
      infarction not in free form but as complex.
AB  - Fourteen monoclonal antibodies (mAbs) against human cardiac troponin I (cTnI)
      were generated by commonly used experimental techniques. All these antibodies, as
      well as antibody 414 (HyTest), were specific for human cTnI. Fifteen antibodies
      thus obtained were tested in a sandwich cTnI immunofluorescence assay (altogether
      196 combinations). Ten pairs giving the highest sensitivity were selected for
      further investigation. The effect of TnI-TnC complex formation on antibody
      interaction with antigen was analyzed. The formation of TnI-TnC complex results
      in a significant decrease of the interaction of mAbs with TnI for seven of 10
      analyzed pairs of antibodies. Using two pairs of cTnI-specific mAbs, one that
      recognized only free cTnI but not cTnI complexed with cTnC, and another that
      could be used for measurement of total cTnI (free cTnI and cTnI in complex with
      cTnC), we demonstrated that the main part of cTnI in serum collected from acute
      myocardial infarction patients is presented in the complex from. We concluded
      that effective and reliable immunological detection of TnI is possible only when
      antibodies used for assay development recognize both free TnI and TnI complexed
      with other troponin components.

PMID- 9267318
TI  - Determination of urinary free cortisol by HPLC.
AB  - We here report a reversed-phase HPLC method for the determination of free
      cortisol in human urine, using methylprednisolone as the internal standard.
      Before chromatography, samples were extracted with a C18 solid-phase extraction
      column and the steroids were separated on a LiChrospher 100 C18 column with a
      mobile phase of methanol/acetonitrile/water (43/3/54 by vol). Linearity,
      precision, and accuracy of the method were established. The detection limit was
      10 pmol of cortisol, and total CVs were < 8%. With various solid-phase extraction
      columns the recovery of cortisol was 36-97%; recovery of the internal standard
      was 43-85%. Study of interference by 6 other steroids and metabolites and 24
      drugs showed that carbamazepine and digoxin partly overlapped with cortisol, but
      this interference could be reduced by modification of the mobile phase. The HPLC
      method was compared with an RIA and an automated immunoassay method. The results
      obtained by HPLC averaged 40% of the RIA values.

PMID- 9267319
TI  - Effect of anti-thyroid peroxidase (TPO) antibodies on TPO activity measured by
      chemiluminescence assay.
AB  - A chemiluminescence method was developed to measure thyroid peroxidase (TPO)
      activity and the inhibitory effect of anti-TPO antibodies in purified porcine
      TPO. The TPO preparation was characterized kinetically and controlled by Western
      blotting technique. The chemiluminescence method proved to be reproducible and
      much more sensitive than the widely used guaiacol method, being able to detect
      TPO concentrations of 2.21 x 10(-5) g/L vs 6.63 x 10(-2) g/L with the latter.
      Otherwise, the determinations with the two methods correlated well (r = 0.76).
      Investigating the effect of IgGs from 23 hypothyroid patients on measured TPO
      activity, we detected inhibition in 19 cases with the chemiluminescence technique
      (15 with the guaiacol method). Anti-TPO antibodies showed competitive inhibition
      of TPO activity with respect to the substrate guaiacol. In both systems, the
      inhibition is present in the IgG F(ab')2 fragment. We conclude that the high
      sensitivity of chemiluminescence detection allows routine determination of the
      inhibition of TPO activity by anti-TPO antibodies.

PMID- 9267321
TI  - Use of filter paper for sample collection and transport in steroid pharmacology.
AB  - Field studies of androgen pharmacology are complicated by the necessity to
      collect, process, and store blood samples in a central facility. We have assessed
      the feasibility of using capillary blood spots collected by fingerprick and dried
      on filter paper for pharmacokinetics and pharmacodynamic measurements with
      nandrolone and testosterone RIAs modified for extracts from capillary blood
      spots. Assays on punched spots of 7.9-mm diameter (14.9 microL of dried blood)
      permitted accurate quantification of testosterone down to 0.4 nmol/L from a
      single spot and nandrolone down to 0.9 nmol/L from two spots. Stability of the
      steroids in dried blood spots to adverse environmental conditions, notably
      increased temperatures, was investigated both in the laboratory and in field
      studies of dried spots sent through the postal system. Storage or postal
      transport under moderate conditions appeared to have no deleterious effects on
      apparent androgen concentrations. However, under extreme conditions of storage at
      50 degrees C for a week or more, or transport to a very hot tropical location, a
      rise in the final concentration of nandrolone, and, to a lesser extent,
      testosterone when corrected for tracer recovery, was noticed. These effects were
      largely due to apparent susceptibility of tritiated tracer, but not unlabeled
      androgen, to thermal degradation. In a pilot pharmacological study involving
      intramuscular injection of 100 mg of nandrolone decanoate in 1 mL of arachis oil,
      nandrolone concentrations in concurrently collected plasma as well as venous and
      capillary blood spots showed good agreement. Testosterone concentrations in
      contemporaneously collected plasma and venous blood spots also showed very good
      agreement. We propose that these methods may allow patients and experimental
      subjects to self-collect samples at remote or field locations for convenient
      mailing to a central laboratory for androgen assay. Applications of this
      methodology are now under way.

PMID- 9267320
TI  - Radioimmunoassay of cortisone in serum, urine, and saliva to assess the status of
      the cortisol-cortisone shuttle.
AB  - We have developed a new assay for cortisone (E) in serum, saliva, and urine
      involving Celite chromatography followed by RIA with 125I-labeled E and
      scintillation proximity assay. The chromatography step separates cortisol (F)
      from E, and in combination with their RIAs, permits assessment of the status of
      the F-E shuttle. We report the results of basal, postcorticotropin (ACTH), and
      postdexamethasone E and F concentrations and their circadian fluctuations in the
      serum, saliva, and urine of healthy volunteers. The serum and urine F/E ratios
      were increased in patients with ectopic ACTH secretion, whereas in adrenal
      adenoma and Cushing disease only the urinary ratio was increased. In chronic
      renal insufficiency this ratio was increased in serum (23.5 +/- 3.9) but
      diminished in saliva (0.38 +/- 0.11), and in apparent mineralocorticoid excess
      the ratios were high in serum (44.3 +/- 9.3) and urine (5.35 +/- 0.85) compared
      with those of healthy subjects (serum 9.8 +/- 3.5, urine 0.52 +/- 0.29, saliva
      0.52 +/- 0.29).

PMID- 9267322
TI  - Isolation and characterization of a digoxin-like immunoreactive substance from
      human urine by affinity chromatography.
AB  - A series of observations has suggested that one or more digoxin-like
      immunoreactive substances (DLIS) in biological fluids is able to cross-react with
      the antidigoxin antibody. Whether this substance is the endogenous inhibitor of
      Na+/K+ ATPase has not been well established. The aim of this study was to
      identify and characterize DLIS from human urine. Treated urine from healthy men
      was run on an affinity chromatography column at a flow rate of 1 mL/min in which
      the ligand was an antibody (antiserum) to digoxin. Eluates from affinity
      chromatography were applied onto analytical reversed-phase HPLC. The active
      material was eluted with a linear gradient of acetonitrile (from 350 to 650 mL/L)
      and water. A second step in HPLC was carried out isocratically with 280 mL/L
      acetonitrile in water. We found a single peak showing cross-reactivity with
      antidigoxin antibody as measured by RIA. It showed the same retention time as
      that of a digoxin calibrator. This highly purified substance is able to displace
      [3H]ouabain from dog kidney-derived Na+/K+ ATPase, to inhibit Na+/K+ ATPase
      activity as measured by the 86Rb+ uptake in red blood cells and by coupled enzyme
      assay. Our results are consistent with the hypothesis that DLIS, as isolated by
      this particular digoxin antibody, is a single substance and an inhibitor of
      Na+/K+ ATPase.

PMID- 9267323
TI  - Amino acid determination in biological fluids by automated ion-exchange
      chromatography: performance of Hitachi L-8500A.
AB  - The Hitachi L-8500A is a newly available apparatus for amino acid (AA) analysis
      that allows automatic on-line mixing of the ninhydrin reagent. The within-run
      precision (human plasma pools at three different concentrations) showed CVs <
      3.8% except for the lowest concentration of citrulline (4.4%), Tyr (4.5%), and
      alpha-aminobutyric acid (7.6%), and for the intermediate concentration of Asp
      (8.7%). Between-run precision (CV) was < 3.1% for 17 AAs and < 8.0% for 24 of 25
      AAs (CV Asp = 12.0%). For retention times, within-run precision was < 0.4% and
      between-run precision < 1.8%. Excellent relations were found between the results
      from the Hitachi L-8500A and the widely used Beckman 6300 analyzer (0.929 < or =
      r < or = 0.999). The detection was still linear at 5 mumol/L except for Pro and
      hydroxyproline (20 mumol/L). The upper limit was at least 2500 mumol/L for 13 AAs
      and at least 1000 mumol/L for 27 of 29 AAs (anserine = 500, Val = 600 mumol/L).
      Values from 100 human plasma samples agreed with previously published data. We
      conclude that the results obtained with the Hitachi L-8500A are satisfactory when
      compared with those of other AA analyzers utilizing the same method. Furthermore,
      the Hitachi L-8500A displays several advantages including programming
      flexibility, microsample capacity, low noise plotting, ammonia filtering, and
      manual repacking of the analytical column.

PMID- 9267324
TI  - Measurement of serum iohexol by determination of iodine with inductively coupled
      plasma-atomic emission spectroscopy.
AB  - We used inductively coupled plasma-atomic emission spectroscopy to measure serum
      iodine to determine plasma clearance of iohexol, an iodinated radiographic
      contrast agent. We determined I at 178.276 nm on the phosphorus 178.287 nm
      channel of the polychromator by utilization of spectrum shifter offset software,
      while correcting for P with the sequential P 214.914 nm emission line.
      Determination of I on the polychromator provided excellent precision in the
      measurement of serum I, even though the interelement correction of P was done
      with a sequential P line. Total imprecision (CV) (n = 13) was 16% (at 13.7 mg/L
      I), 8.6% (28.7 mg/L), 3.6% (59.0 mg/L), 2.6% (120.5 mg/L), 1.7% (237.8 mg/L),
      1.2% (478.7 mg/L), and 1.8% (597 mg/L). The linear range was 15 to 600 mg/L.
      Iohexol added to serum (mg/L I) and recoveries (%) were 15 (91.3%), 30 (95.7%),
      60 (98.3%), 120 (100.4%), 240 (99.1%), 480 (99.7%), and 600 (99.5%). Studies on
      dogs and cats administered a single intravenous injection of iohexol indicated
      that a dose of 300 mg I/kg body weight was sufficient for measurement of
      glomerular filtration rate by using a single compartment model for plasma
      clearance with three samples drawn 3 to 7 h after treatment. With this protocol,
      correlation coefficients were > 0.99 on the beta phase of the plasma
      disappearance curve.

PMID- 9267325
TI  - Suitability of chemical in vitro models to investigate LDL oxidation: study with
      different initiating conditions in native and alpha-tocopherol-supplemented LDL.
AB  - Isolated human LDL, used in the native form or supplemented with alpha-tocopherol
      (alpha T), were oxidized with Cu2+, 2,2'-azobis-(2-amidino propane) hydrochloride
      (AAPH), and H2O2 plus horseradish peroxidase (HRP). The oxidation kinetics were
      measured spectrophotometrically at 234 nm to follow the formation of conjugated
      dienes and evaluated as resistance to oxidation (lag phase, LP) and maximal
      oxidation rate (propagation rate, PR). The duration of LP in nonsupplemented LDL
      was different with the three prooxidant stimuli (LP, in min: 96 +/- 19 for Cu2+,
      28.7 +/- 6.7 for HRP, and 67.1 +/- 11.2 for AAPH). No correlation was found
      between the values obtained with Cu2+ and AAPH or HRP, but a significant
      correlation was found with AAPH and HRP (r = 0.798, P < 0.002). In vitro alpha T
      supplementation prolonged the LP and decreased the PR with all the stimuli. The
      extent of increase in LP was highly correlated (r = 0.872, P < 0.001 for Cu2+ and
      HRP; r = 0.603, P < 0.03 for Cu2+ and AAPH; r = 0.749, P < 0.005 for AAPH and
      HRP). Although the evaluation of ex vivo LDL oxidation is dependent on the
      prooxidant stimulus, the three prooxidant conditions used detect equally well the
      efficiency of alpha T supplementation in preventing LDL oxidation.

PMID- 9267327
TI  - Prostate-specific antigen expression in a case of intracystic carcinoma of the
      breast: characterization of immunoreactive protein and literature surveys.
AB  - A case is presented of female breast intracystic carcinoma with prostate-specific
      antigen (PSA) expressed in high amounts in aspirated cystic fluid (55
      micrograms/L). Tumor extract analysis revealed the presence of both estrogen and
      progesterone receptors (0.38 and 1.87 nmol/L, respectively) and high quantities
      of PSA too (19.52 micrograms/L). Chromatographic analysis of cystic fluid
      revealed two peaks of PSA, at the expected positions for free and bound serine
      protease. A major proportion of 33-kDa free from was also confirmed by Western
      blotting analysis. Free PSA was heat-stable at 56 degrees C and displayed no
      change after freezing-thawing. These findings are discussed in the context of a
      detailed literature survey. Our data support the contention that PSA
      immunoreactivity in intracystic fluid of breast carcinoma is partly the result of
      secretory activity by the neoplastic cells and that the steroid receptors can
      also modulate its expression.

PMID- 9267326
TI  - Binding of nitric oxide to thiols and hemes in hemoglobin H: implications for
      alpha-thalassemia and hypertension.
AB  - Our earlier studies suggested an association between alpha-thalassemia and
      hypertension. We postulated that this association might involve trapping of the
      vasodilator nitric oxide (NO) by hemoglobin (Hb). Hb A has recently been shown to
      carry NO on its sulfhydryl groups in addition to its hemes. In this report we
      studied the interaction of purified Hb H as well as Hb A with NO. The number of
      reactive sulfhydryls were determined spectrophotometrically with bis
      dithionitrobenzoate. Spectral studies and nitrosothiol measurements after
      treatment with NO or nitrosothiols indicated that all eight reactive sulfhydryls
      of Hb H were capable of binding NO. Hb A, however, was only able to bind and
      transfer two molecules of NO per tetramer. These findings support the biochemical
      basis for the association between alpha-thalassemia and hypertension.

PMID- 9267328
TI  - Cardiac troponin T in serum as marker for myocardial injury in newborns.

PMID- 9267329
TI  - Ferritin is not an indicator of available hepatic iron stores in anemia of copper
      deficiency in rats.

PMID- 9267330
TI  - Electrochemical enzyme immunoassay for serum prostate-specific antigen at low
      concentrations.

PMID- 9267331
TI  - Prostate-specific antigen in ascitic fluid.

PMID- 9267332
TI  - PCR reagents for detection of (CAG)n repeats in Huntington disease.

PMID- 9267333
TI  - An urgent use for hemoglobin A1c?

PMID- 9267334
TI  - Rapid, highly sensitive immunoassay for determination of cardiac troponin I in
      patients with myocardial cell damage.

PMID- 9267335
TI  - Prostate-specific antigen is not increased in young men by ultraendurance sport
      performances.

PMID- 9267336
TI  - Ciba Corning ACS:180 direct total testosterone assay can be used on female sera.

PMID- 9267337
TI  - Oxaprozin and 5-(p-hydroxyphenyl)-5-phenylhydantoin interference in phenytoin
      immunoassays.

PMID- 9267338
TI  - [Coronary heart disease in patients with end-stage kidney failure].

PMID- 9267340
TI  - Arteriosclerotic femoral artery aneurysms. A short review.
AB  - True arteriosclerotic aneurysms of the femoral artery are rare but they are
      dangerous lesions that may thrombose, embolise or rupture. They are often
      bilateral and frequently the patient has other aneurysms in the abdominal aortic
      or popliteal artery. True femoral aneurysms were originally classified by Cutler
      and Darling in 1973 as type 1 and type 2 according to their relationship to the
      common femoral bifurcation. Case reports of isolated superficial and profunda
      femoral artery aneurysms have been published, but these are exceedingly rare
      although isolated aneurysms of the profunda femoris artery may be more common in
      Denmark. True femoral artery aneurysms are attributed to weakening of the
      arterial wall due to atherosclerosis. True femoral artery aneurysms are
      relatively rare and are found in elderly smoking men. Aortic aneurysms are
      approximately 10 times more common. Distal embolization occurs in 0-26% of cases.
      Acute thrombosis occurs in around 15% of cases. Rupture is uncommon and varies
      between 10% and 14%. Aneurysmal dilatation of the profunda femoris artery is
      uncommon and occurs in only 1% to 2.6% of all femoral artery aneurysms.
      Individualized operative approaches are based on aneurysmal involvement of the
      superficial femoral or profunda femoris arteries, as well as the presence or
      absence of coexisting extremity occlusive disease. Aneurysm excision and
      interposition or bypass graft reconstruction are favored over direct end-to-end
      reanastomosis.

PMID- 9267339
TI  - Results of carotid surgery in elderly patients.
AB  - METHODS: We have evaluated the results of carotid surgery in 252 patients of 75
      years and over age (A group) including 281 interventions between June 1st 1985
      and December 31st 1993. RESULTS: These results have been compared to those
      obtained in 660 patients of less 75 years (B group), operated on over the same
      period of time (741 interventions). In the A group, the mean age was 78.2 (from
      75 to 89) and 37.3% were women. Nicotinism, obesity and dyslipaemia was
      significantly more frequent in A group. An angor was shown in 48% in A group
      (versus 38.8% in B group). In A group, 34.5% (n = 97) of patients were
      neurologically asymptomatic against 41.7% (n = 309) in B group. Four patients
      aged over 75 died (1.42% per intervention), one from myocardial infarction, the
      other from postoperative stroke. Three other patients showed a non regressive
      postoperative neurological deficiency. The Cumulated Rate of Mortality Morbidity
      (CRMM) in A group is then 2.49% per intervention. It does not significantly
      differ from B group results: mortality = 1.48% (n = 11, 10 of neurological
      origin), CRMM = 3.23% per intervention. We counted 4 myocardial infarctions
      (1.58%) in A group and 5 (0.75%) in B group. The mean time after the
      interventions was 58 months. The five years actuarial survival is 73% of A group
      patients and 85% for B group patients. In A group patients, 44% of deaths are of
      coronary origin and 35% in B group patients. The actuarial rate of people free
      from neurological deficiency, after 5 years, is 90.9% in A group and 92.4% in B
      group. CONCLUSIONS: In this study, age does not seem to be a risk factor in
      carotid surgery. The elderly patients must be selected according to the same
      criteria as the under 75, save the estimation of intellectual faculties and
      autonomy.

PMID- 9267341
TI  - Extracranial carotid artery aneurysms.
AB  - BACKGROUND: Extracranial carotid aneurysms are quite rare diseases. Their
      importance is linked both to critical localization and natural history which can
      lead to neurological events such as TIA and stroke. The importance of an accurate
      diagnosis is related to the necessity to carry out an early repair of these
      lesions and so to achieve the prevention of serious complications with minimal
      surgical risk. MATERIALS AND METHODS: At the Department of Vascular Surgery of
      the University of Florence from January 1982 to December 1995, 2138 surgical
      procedures on extracranial carotid arteries carried out. Twenty-one (0.98%) were
      performed for aneurysms. On the basis of clinical history and instrumental
      findings we divided the patients into three groups: atherosclerotic aneurysms
      (AA, 10 cases), dysplasic aneurysms (DA, 6 cases) and pseudoaneurysms (PA, 5
      cases). RESULTS: Global mortality and major morbility rate was 4.7% (one patient
      suffered perioperative stroke). Eighteen (85.7%) were followed by echo color
      Doppler. No one stenosis and/or dilatation of operated vessel was observed during
      the mean follow-up period of 24 months. In one case (5.5%) of pseudoaneurysms
      group an asymptomatic internal carotid artery occlusion was discovered 3 months
      after surgery. CONCLUSIONS: In our experience, surgical treatment of extracranial
      carotid aneurysms is associated with satisfactory results and low incidence of
      perioperative complications that justified an extensive and early surgical
      therapy.

PMID- 9267342
TI  - Surgical treatment of popliteal artery aneurysm. A 20 year experience.
AB  - OBJECTIVES: A retrospective study to evaluate the treatment, long term follow-up
      and factors affecting revascularization results particularly in regard to
      clinical presentation and prosthetic materials used after 20 years of experience.
      MATERIALS AND METHODS: Between 1974 and September 1995 there were 67 popliteal
      aneurysms in 58 patients. Three patients underwent a primary amputation because
      of irreversible ischaemia and 3 patients a surgical sympathectomy. Operative
      repair was performed in 61 cases: as an emergency in 9 (14.7%) limbs and as an
      elective procedure in 52 (85.3%) limbs. Graft replacement was performed employing
      polytetrafluoroethylene (PTFE) grafts in 34 (55.7%) cases 13 of which with Ringed
      PTFE, autogenous saphenous vein in 10 (16.4%) cases and Dacron in 17 (27.9%).
      RESULTS: The cumulative primary patency (CP) and limb salvage rate (LS) at 10
      years were 75.1% and 83.3% respectively. We divided the patients into two groups:
      asymptomatic (Group I) and symptomatic with limb threatening ischemia (Group II).
      At 10 years the CP in Group I and II were 78.2% vs 67.2% respectively (p < 0.05
      at 18 months) and the LS 87.4% vs 74.6% (p < 0.05). There was no statistical
      difference in terms of CP and LS rate between saphenous vein and PTFE. The use of
      PTFE grafts avoided harvesting of the long saphenous vein; this resulted in a
      significantly reduced operation time (135 +/- 18.6 vs 195 +/- 22.4 minutes, p <
      0.001) and length of stay (7.4 vs 8.8 days, p < 0.02). CONCLUSIONS: We conclude
      that elective repair is indicated in all patients with popliteal aneurysm > or =
      2 cm to avoid a critical ischemia with poorer results in terms of CP and LS. In
      the last 3 years our technique of choice is the exclusion of the aneurysm with a
      short PTFE bypass with good long-term of CP and LS rates.

PMID- 9267343
TI  - Mycoplasma in urine and blood following catheterisation of patients undergoing
      vascular surgery.
AB  - OBJECTIVES: The purpose of this investigation was to determine if mycoplasmas
      enter the bloodstream after urinary tract catheterisation in patients undergoing
      vascular surgery in order to evaluate the efficiency of the routine prophylactic
      antibiotic treatment. DESIGN: Prospective study. MATERIALS AND METHODS: A total
      of 100 patients (63 men and 37 women) undergoing elective vascular surgery had
      urine and blood cultures performed for mycoplasmas. Blood cultures were taken
      preoperatively after urinary tract catheterisation and the urine was collected
      during catheterisation. The median age of the patients was 67 years (range 42
      87). RESULTS: A total of 12 (12%), 5 men and 7 women, had a positive urine
      culture for mycoplasmas (One patient had Mycoplasma hominis and 11 had Ureaplasma
      urealyticum isolated). Their median age was 60 years (range 42-76). No blood
      cultures were positive for Mycoplasma. CONCLUSIONS: Mycoplasmas do not enter the
      blood-stream after catheterization in sufficient amounts and sufficiently often
      to be detected by blood-cultures in this small patient sample. The number of
      vascular patients harbouring mycoplasmas in the urine was low and we found no
      indication for changes in the prophylactic antibiotic treatment based on these
      findings.

PMID- 9267344
TI  - The inhibition of canine vein graft intimal thickening using a newly developed
      antiplatelet agent.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy of a newly
      developed antiplatelet agent, 4-cyano-5, 5-bis[methoxyphenyl]-4-pentenoic acid
      (E5510) on intimal hyperplasia of experimental autologous vein grafts in a distal
      poor runoff canine model. METHOD: The femoral vein was implanted into the femoral
      artery preparing a distal poor runoff model. These animals were divided into
      three groups consisting of the E5510 group, the Aspirin group, and the Control
      group. The vein grafts were harvested at either 1 or 4 weeks after implantation.
      RESULTS: At 4 weeks, the degree of intimal hyperplasia of the graft of E5510
      group was significantly less than that of the Aspirin group and the Control group
      (p < 0.05). No significant difference was observed between the Aspirin group and
      the Control group. At 1 week, the degree of intimal cell proliferation was
      determined by bromodeoxyuridine (BrdU) incorporation and was expressed as the
      BrdU labeling index. The BrdU labeling index of the E5510 group was also
      significantly lower than that of the Control group (p < 0.05). CONCLUSIONS: These
      data demonstrate the efficacy of E5510 in reducing intimal hyperplasia of vein
      grafts under distal poor runoff conditions by reducing the degree of smooth
      muscle cell proliferation.

PMID- 9267345
TI  - Anomalous inferior vena cava complicating abdominal aortic aneurysmectomy.
AB  - Variations in the site and course of the inferior vena cava (IVC), although
      relatively infrequent, can have important surgical implications, especially
      during surgery for abdominal aortic aneurysm. We report two cases of left-sided
      IVC encountered during aneurysmectomy. In both cases, the anomaly was not
      detected during preoperative ultrasound examination, but was identified by CT
      scan in one case. Careful mobilization of the IVC and left iliac vein allow
      retraction of the IVC to the right, after which the aneurysm can be approached in
      the usual manner.

PMID- 9267346
TI  - Infected abdominal aortic aneurysm: in situ replacement with cryopreserved
      arterial homograft.
AB  - Infected aortic aneurysms are a rare (1.3% of all abdominal aortic aneurysms) but
      life-threatening disease. At present controversy continues about the specific
      diagnosis and the best surgical management. We present one case of infected
      aortic aneurysm treated with in situ reconstruction with cryopreserved arterial
      homograft. He was a 50-year-old man with recent history of pneumococcal
      meningitis who is readmitted because he suffered a stroke and during physical
      examination a pulsatile abdominal mass was discovered. Blood cultures were done
      and the result was repeatedly negative. Radiological studies were performed: the
      abdominal CT scanning showed a non ruptured 5 cm infrarenal aortic aneurysm with
      irregular wall and in the aortography it appeared eccentric, multilobulated with
      a clear neck in an otherwise normal size aorta but with some arteriosclerotic
      lesions. The diagnosis of infected aneurysm was suspected and the patient
      received antibiotic therapy and was operated on: aneurysm resection with wide
      debridement of surrounding tissues and in situ aortic replacement with
      aortobifemoral cryopreserved arterial homograft. Cultures of the aneurysm wall
      and contents were negative but aneurysm wall biopsy suggested an infected aortic
      aneurysm. The postoperative course was uneventful and antibiotics were continued
      for 6 weeks. The patient is doing well 7 months after surgery without signs of
      recurrent infection and normal appearance of the cryopreserved arterial
      homograft. We conclude that specific diagnosis of infected aortic aneurysms is
      essential for correct treatment but may be difficult, in these cases a history of
      infection supported by radiologic findings and aneurysm wall biopsy are of great
      value. Cryopreserved arterial homografts constitute a good alternative to
      prosthetic grafts for in situ reconstructions in the treatment of infected aortic
      aneurysms, decreasing the risk of re-infection or septic complications.

PMID- 9267347
TI  - Spontaneous and isolated dissection of the common iliac artery.
AB  - A patient with isolated dissection of the common iliac artery is presented. A 56
      year-old man was admitted because of sudden intermittent claudication of the left
      lower limb. Angiography showed a left popliteal artery interruption associated
      with an asymptomatic dissection of the right common iliac artery. The patient was
      treated with a left femoropopliteal bypass and a right aortofemoral bypass. The
      etiology of primary dissections of peripheral arteries is discussed.

PMID- 9267348
TI  - Takayasu's arteritis complicating annuloaortic ectasia (AAE) treated with
      modified Bentall procedure.
AB  - A case report and a brief review of the literature on Takayasu's arteritis
      complicating annuloaortic ectasia are presented. The patient successfully
      underwent modified Bentall procedure during the inactive stage of the disease.
      Piehler's method is recommended for coronary reconstruction in the presence of
      severe periaortic adhesions resulting from Takayasu's arteritis.

PMID- 9267349
TI  - An aneurysm of the right gastroepiploic artery.
AB  - A palpable mass was unexpectedly found in the upper abdomen of a 67-year-old
      woman. Computed tomography (CT) and abdominal angiography both indicated an
      aneurysm of the right gastroepiploic artery. An aneurysmectomy was performed, and
      the aneurysm was found to be spherical with a diameter of 7.5 x 7.7 cm. The
      patient was eventually discharged in good condition. The histological findings of
      the aneurysmal wall revealed medial fibrosis and atherosclerosis. Gastroepiploic
      artery aneurysms are rare among splanchnic artery aneurysms and most such
      aneurysms are found to be ruptured. The present report described a quite rare
      case of an asymptomatic giant gastroepiploic artery aneurysm and also includes a
      review of the 10 reported cases of gastroepiploic artery aneurysms in the English
      literature to date. Since gastroepiploic artery aneurysms have a high risk of
      rupture it is essential that appropriate surgical measures be taken immediately.

PMID- 9267350
TI  - Surgical therapy for coronary artery disease in patients with a left ventricular
      ejection fraction of 25% or less.
AB  - BACKGROUND: In patients with advanced coronary artery disease (CAD) and markedly
      decreased left ventricular ejection fraction (EF) symptoms of myocardial ischemia
      and insufficiency may be complicated by ventricular arrhythmias. Appropriate
      surgical therapy must be tailored to the individual symptoms. The aim of this
      study was to compare the different current methods. METHODS: From 9/1990 to
      9/1994 138 patients with coronary artery disease and a left ventricular EF of <
      or = 25% were operated. Patients with dominating Angina pectoris and vital
      myocardium were revascularized (ACB; n = 17); two of these patients were 12 and
      37 months p.o. transplanted. Because of dominating dyspnea, diffuse CAD and
      missing AP heart transplantation seemed indicated (HTX; n = 102). In two of these
      patients ventricular assist devices were implanted as a bridge to
      transplantation; both patients survived. Patients with malign tachycardias
      received either an implantable cardio-defibrillator (ICD; n = 16) or had
      arrhythmia surgery (ARS; n = 3). Patients of the HTX-Group were younger (54 vs 60
      years; p < 0.05), had more often previous surgery (28% vs 20%) and were in worse
      conditions (NYHA 3.5 vs 3.0; p < 0.05). RESULTS: The main cause of death after
      transplantation was multi-organ failure (MOF; 14/102; 13.8%). The best long-term
      survival (87% after 3.2 years, p < 0.01 vs HTX)-with low average functional
      classes (NYHA 2.9)-had the patients after ICD implantation. The best quality of
      live (NYHA 1.1; p < 0.01 vs ICD)-associated with a high mortality due to
      preoperatively impaired organ-systems (62% operative survival, 57% 4-years
      survival)-was achieved by transplantation. In patients with a history of
      ventricular arrhythmias, who are waiting for a transplantation, the implantation
      of an ICD should be considered. Bypass surgery as well as arrhythmia surgery
      showed good survival (1-year survival 82% and 66% respectively) and functional
      results (NYHA 1.7 and 1.5 respectively).

PMID- 9267351
TI  - The effect of preoperative intra-aortic balloon pump support in high risk
      patients requiring myocardial revascularization.
AB  - The intra-aortic balloon pump (IABP) is an established additional support to
      pharmacologic treatment of the failing heart after myocardial infarction,
      unstable angina and cardiac surgery. The physiologic effect of IABP are:
      increased coronary perfusion and decreased left ventricular outflow impendance.
      The effects of preoperative IABP are not established. The aim of this study was
      to define indications and evaluate the effect of preoperative IABP support.
      Between January 1, 1990 and December 31, 1994, 1999 patients underwent CABG [318
      REDOCABG, 15.9% and 1681 primary CABG, 84.9%]. From January to June 1994, 80 of
      1811 patients (4.5%) required additional intra-aortic balloon pump (IABP) support
      postoperatively, 35 after REDO (21%) and 45 after primary CABG, 3%. Indication
      for IABP was failure to wean from cardiopulmonary bypass (CPB), despite maximal
      dose pharmacological support. The overall hospital mortality was 11.6% after
      REDO's and 2.1% after primary CABG, p < 0.001. In those where IABP was required
      the mortality rate was 67.7% after REDO and 36.8% after primary CABG, p < 0.01.
      Multivariate analysis identified preoperative unstable angina as independent risk
      factor for mortality (p < 0.001). REDO-CABG, LVEF < 40%, diffuse coronary artery
      disease and left main stem stenosis were identified as riskfactors for mortality
      when combined with one and another in a combination of at least two factors. In
      the IABP supported group mean ICU stay was 5.4 +/- 1.8 days. Thereafter the
      concept of preoperative use of IABP was introduced and presence of at least two
      of the above identified riskfactors served as indication for preoperative IABP
      treatment. The IABP was placed in the operating room at induction of anesthesia
      (1-1.5 hr prior to cross-clamping). Between June and December 1994, 19 of 188
      patients received a preoperative IABP (9.0%). There were no balloon related
      complications. The mortality rate was 21%. Weaning from CPB was easy and in 30%
      of the cases the IABP was not necessary postoperative. In 90% of the pumps were
      removed within 24 hours postoperative. The mean ICU stay was 2.1 +/- 0.9 days.
      The first part of this study identified riskfactors for mortality after CABG and
      in the second series the efficacy of preoperative IABP treatment in "high-risk"
      patients was demonstrated. Preoperative IABP support in these patients seems also
      cost efficient due to lower mortality and shorter stay in intensive care unit in
      this group of patients.

PMID- 9267352
TI  - Orthotopic heart transplantation for dilated cardiomyopathy in a patient with
      persistent left superior vena cava and atresia of the right superior vena cava.
AB  - OBJECTIVE: To describe the surgical procedure of an orthotopic heart
      transplantation in a recipient with persistent left superior vena cava and
      atresia of right superior vena cava. EXPERIMENTAL DESIGN: Case report. PATIENT: A
      43 year old male with persistent left superior vena cava, atresia of the right
      superior vena cava and dilated cardiomyopathy. INTERVENTIONS: Orthotopic heart
      transplantation with selective cannulation of the left superior vena cava via
      recipient coronary sinus for cardiopulmonary bypass. RESULTS: No perioperative
      complications, satisfactory postoperative course. No rejection episodes at 7
      months postoperative with non invasive procedure surveillance. CONCLUSION:
      Technique described to preserve left superior vena cava is a useful alternative
      for this patient with no surgical complications.

PMID- 9267353
TI  - Left thoracotomy for reoperative revascularization of the posterior coronary
      circulation.
AB  - Reoperative sternotomy for repeat coronary artery revascularization is known to
      have increased morbidity and mortality when compared to first time sternotomy.
      The increased risk involve damage to the heart itself, injury to previously
      placed bypass grafts, embolization of debris from manipulation of diseased grafts
      leading to possible myocardial infarction as well as the numerous other hazards
      which may complicate a difficult reoperative dissection. The use of the left
      thoracotomy for reoperative revascularization of the left thoracotomy for
      reoperative revascularization of the posterior coronary circulation avoids to the
      usual hazards of reoperative sternotomy. This approach allows for easy access to
      the posterior circulation not only for vein graft placement but also for the use
      of the mammary artery for grafting when necessary. Through the use of an
      illustrative case report and the discussion of previously reported cases the
      technique of the procedure as well as its variations and applications is
      described. The technique of left thoracotomy for reoperation revascularization in
      selected cases represents a useful alternative in the armamentarium of cardiac
      surgeon.

PMID- 9267354
TI  - Rupture of a dissecting aneurysm into the superior vena cava in Marfan's
      syndrome.
AB  - Aneurysmal dilatation of the aorta with subsequent dissection or rupture occurs
      frequently in patients with Marfan's syndrome. These complications are among the
      major causes of death. We report the case of a 51-year-old man with annulo-aortic
      ectasia in Marfan's syndrome. Acute aortic dissection and rupture into the
      superior vena cava occurred 8 years after aortic valve replacement. The
      preoperative diagnosis was made by right heart catheterization and computed
      tomography. A markedly increased left-to-right shunt occurred with rapid
      enlargement of the fistula due to the fragility of the aortic wall characteristic
      of Marfan's syndrome. Postmortem examination demonstrated severe medial necrosis
      with rupture of the aortic wall into the superior vena cava which was adherent to
      the suture line of the aortotomy from the previous surgery. Type A aortic
      dissection with severe congestive heart failure strongly suggested rupture into
      the pulmonary circulation.

PMID- 9267355
TI  - Coronary artery bypass grafting of Takayasu's disease with calcified aorta and
      subclavian artery obstruction.
AB  - The lesions of Takayasu's disease, which may involve the aorta and major arterial
      branches, may pose technical difficulties during coronary artery bypass grafting
      (CABG). Because the aorta is often thick and calcified, the coronary arterial
      lesion is often located near the coronary orifice, and the internal thoracic
      arteries may not be suitable for grafting due to the lesions in the subclavian
      arteries. A 63-year-old man with a known history of Takayasu's disease was
      referred to our department with chest pain complaint. Coronary angiography
      revealed obstruction of the left main coronary artery. CT scan showed that he had
      a thickened and calcified aorta. Aortography showed that both subclavian arteries
      had obstructive disease. Instead of using ordinary arterial grafts or vein
      grafts, a piece of prosthetic patch carrying saphenous vein grafts was sewn to
      the ascending aorta to construct the proximal anastomosis of CABG. Distal
      anastomosis was made on the left anterior descending artery and the obtuse
      marginal branch in the usual fashion. The patient showed uneventful recovery, and
      a postoperative coronary angiogram showed patent grafts and uncomplicated
      ventricular performance. This technique is useful when the aorta is not suitable
      for vein graft anastomosis and arterial grafts are not available as in this case
      with aortitis reported in the paper.

PMID- 9267356
TI  - Acute aortic dissection without intimal tear.
AB  - A case of acute aortic dissection without intimal tear is reported. A 68-year-old
      woman with acute onset of Stanford type-B aortic dissection was admitted. Because
      of progressive anemia and pleural leakage, an operation was performed. False
      lumen of the descending thoracic aorta was occupied with fresh hematoma, but no
      sign of an intimal defect was found. Although aortic dissection without intimal
      tear has been reported via angiography, CT scan, MRI, and autopsy, surgically
      confirmed cases of this type of dissection have been rarely reported.

PMID- 9267357
TI  - Congenital esophageal stenosis.
AB  - Congenital esophageal stenosis caused by membranous webs occurred in three
      infants. There were no associated anomalies. First patient applied with
      respiratory symptoms while the second and third patients reported food
      impactions. Correct diagnosis was performed during intraoperative (first patient)
      and esophagoscopic examination (second and third patients). Resection and
      anastomosis were performed in the first patient and hydrostatic dilatations in
      the second and third patients. In three patients, symptoms were relieved
      following treatment. In this report, etiology, diagnostic aids and management of
      this rare pathology are discussed.

PMID- 9267358
TI  - Parietal pleurectomy as a method of treatment of recurrent pneumothorax: long
      term functional results.
AB  - A retrospective study of 297 patients treated surgically due to recurrent
      pneumothorax between 1974 and 1990 was performed with special reference to long
      term functional results, compared with preoperative values. Duration of follow-up
      was 5 years. 44 patients from this group were hospitalised twice at our
      department. The first incident of pneumothorax was treated by chest tube
      drainage, the next by parietal pleurectomy. Each time, with both lungs expanded
      VC, MVV and FEV1 were measured. It gave a unique occasion to compare real pre-
      and postoperative spirometric results in the same patient (in other publications
      postoperative results are usually compared to predicted values taken from
      different tables). There was no significant impairment of the mechanical
      efficiency of respiration. Surgical complications were rare and minor with no
      deaths. There were no postoperative recurrences of pneumothorax. This series
      indicates that pleurectomy is a safe and reliable method of protection against
      recurrence of pneumothorax.

PMID- 9267359
TI  - Invasive thymoma extending to the right atrium: excision without cardiopulmonary
      bypass.

PMID- 9267360
TI  - Selegiline and vitamin E in Alzheimer's disease.

PMID- 9267361
TI  - Analgesia during circumcision.

PMID- 9267362
TI  - Testing intervals for PSA test.

PMID- 9267363
TI  - SSRIs, bupropion, and sexual function.

PMID- 9267364
TI  - Best bowel prep for flexible sigmoidoscopy.

PMID- 9267366
TI  - OC failure rates and oral antibiotics.

PMID- 9267365
TI  - Treating shoulder pain: a randomized trial.

PMID- 9267367
TI  - Penciclovir cream for herpes simplex labialis.

PMID- 9267368
TI  - Influenza, influenza vaccine, and amantadine/rimantadine.
AB  - Influenza viruses are highly contagious viruses that are transmitted from person
      to person, usually by the airborne route. Persons in semi-closed or crowded
      environments, such as students and residents of nursing homes, are at high risk
      of exposure. The illness attack rate in children ranges from 14% to 40% yearly.
      Fatality rates are highest in persons who have chronic medical conditions, such
      as chronic obstructive lung disease, cardiovascular disease, and diabetes
      mellitus, particularly if they are elderly. The effectiveness of influenza
      vaccine in preventing or attenuating illness varies, depending primarily on (1)
      the degree of similarity between the virus strains included in the vaccine and
      those that circulate during the influenza season, and (2) the age and
      immunocompetence of the vaccine recipient. When there is a good match between
      vaccine and circulating viruses, influenza vaccine has been shown to prevent
      illness in approximately 70% to 90% of healthy persons less than 65 years of age.
      Adverse events following influenza vaccine include mild, local reactions at the
      injection site (up to 20%) and occasionally fever in approximately 1% of
      vaccinees. Despite the availability of an effective vaccine, only 55% of persons
      65 years of age and older reported receiving influenza vaccine in 1994.
      Vaccination levels are even lower in persons less than 65 years of age with high
      risk medical conditions. Important procedures to improve vaccination rates are
      (1) assessment of a practice's or medical facility's current vaccination rates,
      (2) identification of target populations for vaccination, (3) formation of a
      specific goal (ie, percentage of target population to be immunized), (4)
      development of a plan of action, and (5) provision of ongoing feedback to the
      individual physicians about vaccination rates of their own patients.

PMID- 9267369
TI  - Managed care and discontinuity of primary care providers: is there evidence of
      poorer outcomes?

PMID- 9267370
TI  - Computers for clinical practice--not yet, but soon.

PMID- 9267371
TI  - The impact of insurance type and forced discontinuity on the delivery of primary
      care.
AB  - BACKGROUND: The effect of managed care on important attributes of primary care is
      poorly understood. Of particular concern is the potential for annual bidding on
      managed care contracts, which may cause forced discontinuity of care. We examined
      the effect of insurance type and insurance-mandated disruption in continuity of
      care on the quality of primary care. METHODS: A cross-sectional study design was
      used to examine 1839 patient visits to 138 community-based primary care
      physicians. The quality of primary care delivery was measured with the Components
      of Primary Care Instrument, a patient-reported indicator of physician knowledge
      of the patient, interpersonal communication, coordination of care, continuity of
      care, and patients' preference to see their regular physician. RESULTS: No
      significant differences in any of the five indicators of primary care quality
      were found between patients with independent provider association/preferred
      provider organization (IPA/PPO) and fee-for-service insurance. Patients with
      IPA/PPO health insurance were four times as likely as patients with fee-for
      service insurance to report a forced change in their primary care physician (P <
      or = .01). Individuals forced to change their physician because of changes in
      their health care insurance scored significantly lower on all five indicators of
      primary care quality (P < or = .01). CONCLUSIONS: The quality of primary care
      appears to be less dependent on the payment system than on the maintenance of the
      patient-physician relationship. Forced disruption of continuity of care is
      detrimental to patient receipt of quality primary care, and is a potential
      negative consequence of annual bidding for managed care contracts.

PMID- 9267372
TI  - Family physicians' preferences for computerized decision-support hardware and
      software.
AB  - BACKGROUND: While computers are now widely used by family physicians for billing
      and patient registration purposes, their use as decision-support tools is still
      quite limited. The purpose of this study was to determine the current use of
      computer hardware and software by family physicians, and the characteristics
      these physicians desire in computerized decision-support hardware and software.
      METHODS: A cross-sectional survey of a random sample of 250 Michigan family
      physicians was undertaken in mid-1995. These physicians were asked about their
      current use of a variety of computer hardware and software. They were also asked
      to rate the value of different kinds of decision-support information potentially
      available by computer. The survey instrument also gathered the family physicians'
      preferences for design factors (both hardware and software), such as the size of
      a computer, the time needed to access information, and the frequency of updates.
      RESULTS: Word processing on desktop computers and hospital information systems
      are the most widely used computer applications by family physicians. Physicians
      are most interested in computer-based information on drugs, storage and
      generation of patient education materials, and accessing treatment
      recommendations. Most feel that semiannual or annual updates of information are
      adequate, and would like a uniform interface. A high percentage of physicians
      (84.5% of all physicians and 94.1% of younger physicians) stated that they would
      consider carrying a handheld computer. CONCLUSIONS: There is significant interest
      in several types of clinical decision-support software. Based on the results of
      this study, such software should have following characteristics: (1) be available
      for handheld as well as networked and desktop computers, (2) include drug
      information (particularly warnings, interactions, and side effects), (3) include
      overviews of treatment recommendations, (4) include patient education materials,
      and (5) have a uniform user interface and be updated at least annually.

PMID- 9267373
TI  - Health promotion and screening services reported by older adult patients of urban
      primary care physicians.
AB  - BACKGROUND: Adult preventive services provided at intervals recommended by expert
      panel guidelines may reduce morbidity and mortality. As part of an intervention
      trial to increase primary preventive services in urban primary care practices,
      baseline data were collected on primary prevention and screening test rates in
      older adults and on patient characteristics associated with provision of these
      services. METHODS: A questionnaire on preventive services offered or provided
      over the past 2 years was completed by patients aged 52 to 77 years and another
      by their 42 participating physicians. Logistic regression was used to identify
      patient characteristics associated with increased provision of these services.
      RESULTS: Usable questionnaires were completed by 1457 (80.9%) patients. Patient
      age and sex were not associated with the provision of primary preventive and
      counseling services. The presence of two or more chronic diseases was predictive
      of primary preventive services (P < .02), but was not associated with an increase
      in screening tests or procedures. Age was positively associated with delivery of
      prostate-specific antigen blood tests (P < .001) and rectal examinations (P <
      .001) in men, but was negatively associated with mammography (P < .001) and
      Papanicolaou (Pap) tests (P = .02) in women. The negative trend in screening
      mammography was evident even for women aged 50 to 65 years despite the national
      consensus regarding the benefits of screening for this age group. Patients with
      health management organization insurance reported significantly more mammography
      (P = .002), cervical Pap tests (P = .050), sigmoidoscopies (P = .002), and fecal
      occult blood tests (P = .035). CONCLUSIONS: In our study patients, the provision
      of primary preventive and screening services was closer to consensus guidelines
      than is typically reported in the literature. The data suggest that future
      investigations and interventions to improve primary prevention and screening
      services in older adults who have access to primary care do not need to be
      directed at fundamental changes in the way preventive services are delivered, but
      rather should target procedures of proven benefit, such as mammography, where
      rates remain below recommended guidelines.

PMID- 9267374
TI  - Conduct disorder and antisocial personality in adult primary care patients.
AB  - BACKGROUND: Conduct disorder has been linked to substance use disorders in
      clinical populations. This study examined the relationships of conduct disorder
      and antisocial personality (ASP) disorder to substance use, substance abuse
      problems, depression, and demographic factors in primary care settings. METHODS:
      As part of a larger clinical trial, a survey of 1898 patients in the offices of
      64 primary care physicians was conducted using a self-administered health habits
      questionnaire. Childhood conduct disorder and adult antisocial personality
      disorder were assessed using criteria from the Diagnostic and Statistical Manual
      of Mental Disorders, Third Edition, Revised. RESULTS: Eight percent of men and
      3.1% of women met criteria for a diagnosis of ASP disorder. The frequency of a
      history of childhood conduct disorders was higher, with 13.4% for men and 4% for
      women. Antisocial personality disorder was predicted by male sex, being unmarried
      (single, separated, divorced), lifetime history of depression, binge drinking,
      self-reported history of drug problems, current smoking, and younger age. The
      predictors of a history of child conduct disorder were similar to those of ASP.
      CONCLUSIONS: Primary care physicians treat many patients who have personality
      disorders and other conditions such as alcohol problems and depression. These
      patients need to be identified because of the high potential for comorbidity and
      the barriers to treatment inherent in these disorders.

PMID- 9267375
TI  - The effectiveness and safety of two cervical cytologic techniques during
      pregnancy.
AB  - BACKGROUND: There have been few studies documenting the optimal cervical
      cytologic technique in pregnancy. This study was initiated to investigate the
      effectiveness and safety of two standard techniques. METHODS: Two hundred twenty
      two new obstetrical patients at a family practice residency program signed
      informed consent, were enrolled, and were randomized for cervical cytologic
      screening using either Zelsmyr Cytobrush and Ayre spatula or Dacron swab and Ayre
      spatula. The pathologists were blinded to the study, and results were reported
      with standard Bethesda System nomenclature. Patients were asked about
      complications at follow-up visits. Statistical analysis was performed using
      Fisher's exact test and the two-sample t test, with statistical significance set
      at P < .05. RESULTS: The Cytobrush-spatula technique yielded 95.6% (108/113)
      smears with adequate endocervical cells, as compared with 69.7% (76/109) of
      smears obtained with the Dacron swab and spatula (P = < .0001, odds ratio 9.38).
      Cytologic atypia, defined as noninflammatory cellular abnormalities, was
      uncovered on 15.9% (18/113) of the smears obtained with the Cytobrush and spatula
      technique and on 13.8% (15/109) of the smears obtained with the Dacron swab and
      spatula (P = .7082). The complication rate, which included spot bleeding and
      spontaneous abortion, occurred in 6.5% (7/108) of the smears obtained with the
      Cytobrush and 3.8% (4/105) of the smears obtained with the Dacron swab (P = .54).
      CONCLUSIONS: The Cytobrush-spatula technique significantly increased endocervical
      cell yield, did not increase detection of cytologic atypia, and did not increase
      the risk of adverse maternal or fetal outcomes when used for cervical cytologic
      screening during pregnancy. These results support the use of the Cytobrush
      spatula technique over the swab and spatula for obtaining cervical cytologic
      smears in pregnancy.

PMID- 9267376
TI  - Postpartum psychosis induced by bromocriptine and pseudoephedrine.
AB  - Bromocriptine is an ergot-derived dopamine agonist sometimes used for postpartum
      suppression of lactation. On rare occasions (a total of seven previous reports in
      the literature), use of the medication has been associated with psychotic
      symptomatology in postpartum patients. This case report describes a 19-year-old
      postpartum woman who developed severe psychotic symptoms while taking low doses
      of bromocriptine and pseudoephedrine. The use of bromocriptine for suppression of
      lactation is controversial. If prescribed for postpartum patients, bromocriptine
      alone or in combination with sympathomimetic drugs should be used only with
      caution.

PMID- 9267377
TI  - Cranberry concentrate: UTI prophylaxis.

PMID- 9267378
TI  - Douching frequency.

PMID- 9267379
TI  - Correcting myopia.

PMID- 9267381
TI  - Empowerment: answering the white phone first.

PMID- 9267382
TI  - The Connecticut initiative.

PMID- 9267383
TI  - From chaos to excellence: preparing for a successful Joint Commission survey.
AB  - The new joint Commission on Accreditation of Healthcare Organizations survey
      requirements make the preparation process more challenging than ever before. In
      today's competitive healthcare environment, a successful survey is imperative.
      The authors discuss multiple and innovative ways to prepare for a survey under
      the 1996 guidelines. Specific examples of processes and forms are included.

PMID- 9267384
TI  - Managed healthcare consumer protection initiatives.
AB  - This three part series on health legislation describes the policy shift toward
      regulating the private healthcare system to ensure adequate consumer protection
      and access to health insurance. Still burning from the failed 1993-1994
      healthcare reform effort, Congress and the White House are looking only for
      incremental policies necessary to reduce the federal deficit and protect the
      public white the private healthcare system continues to undergo major
      transformation. In this series, the author discusses Medicare, Medicaid, and
      other federal program revisions: consumer protection legislation aimed at
      unacceptable managed care practices: and incremental health insurance proposals
      aimed toward segments of the uninsured.

PMID- 9267385
TI  - Managed care: changing the way we practice.
AB  - As transformation of the nation's healthcare system continues, one thing is
      certain-managed care is here to stay. It has been shown that the majority of
      people are happy with their managed care plans, and the business sector is very
      happy with its containment of costs. But what about healthcare professionals? Are
      we happy with managed care? Happy or not, we now live in a managed care
      environment and over the next several years, the penetration in our markets will
      increase markedly. How is managed care changing the way in which nurse executives
      practice? The author examines the impact of managed care on executive practice
      and includes interviews with two nurse executives who provide insight into their
      own practice transformation as the result of managed care. Strategies for
      effectively meeting the demands of role transformation related to managed care
      are also presented.

PMID- 9267386
TI  - Challenges for nursing administration educators.
AB  - The council on Graduate Education for Administration in Nursing (CGEAN) was
      established to further develop and improve graduate education for administration
      in nursing. The council seeks to identify the nature and direction of education
      for administration in nursing in various healthcare systems, providing guidelines
      for programs offering administration. A major goal of CGEAN is facilitating
      dialogue between nursing service administrators and graduate level educators who
      are engaged in teaching and research related to administration in nursing. This
      column, sponsored by the members of the Council analyzes and responds to position
      statements and trends related to the delivery of health services and graduate
      education for administrators in nursing.

PMID- 9267387
TI  - Impact of organizational redesign.
AB  - Little in-depth objective information is available about the outcomes of
      restructuring or reengineering. One reason for this is the difficulty of
      conducting traditional research within the context of dynamic organizational
      development activities. The authors describe an alternative program evaluation
      approach that proved successful for assessing and enhancing large-scale
      organizational change in an acute-care medical center. Sample results are
      presented and recommendations made for increasing an evaluation's usefulness by
      tailoring reports to the user.

PMID- 9267388
TI  - A pragmatic approach to measuring and evaluating hospital restructuring efforts.
AB  - Organizations have expended enormous resources to restructure care delivery
      Despite the growing literature describing these organizational innovations there
      is a paucity of credible data that reflects systematic measurement and evaluation
      of such changes. This report not only describes a comprehensive research based
      restructuring effort in a 720 bed acute care hospital, but it also describes an
      outcomes evaluation strategy and associated findings that may serve as a model
      and a guide for other healthcare institutions.

PMID- 9267389
TI  - Multisite clinical research: a challenge for nursing leaders.
AB  - The need for the application of research-based data to diversified healthcare
      systems has led to more attempts by nurse researchers to investigate phenomena
      across clinical sites. Nurse executives increasingly are asked to justify
      resource allocation among organizations, and must compare patient-care practices
      within complex systems that are often geographically distant. This article
      describes the pitfalls encountered and the progress made by researchers during a
      4-year multisite, multimethod clinical investigation collecting clinical outcome
      and organizational context data from seven hospitals.

PMID- 9267390
TI  - Survey and critique of studies related to unlicensed assistive personnel from
      1975 to 1997, Part 2.
AB  - This article is part 2 of a descriptive integrated review of research on the use
      of unlicensed assistive personnel in nursing. Part 1, published last month,
      described the methods used to find and to critique 29 research articles; it
      included the conceptual model and the variables identified in the studies. Part 2
      presents a synthesis of the 29 studies data conclusions, implications and
      recommendations.

PMID- 9267391
TI  - Outbreaks can be disasters: a guide to developing your plan.
AB  - Disaster can strike at any time. Most hospitals have a contingency plan for
      attack from without, but it can also happen from within as one small rural
      hospital discovered. The authors share practical tips for prevention, detection
      crisis management, and post-crisis follow-up based on principles of disaster
      planning. Experience is a great teacher and we can benefit from the authors'
      helpful tips for creating a more complete plan.

PMID- 9267392
TI  - Effect of tunicamycin on the uptake and incorporation of galactose in Hymenolepis
      diminuta.
AB  - The effects of tunicamycin (TM) on the uptake and incorporation of tritiated
      galactose into the tegumental membrane and carcass from adult Hymenolepis
      diminuta were examined to assess the potential usefulness of this inhibitor for
      studying the function of the tapeworm surface glycocalyx. Hymenolepis diminuta
      adults (11 days old) were preincubated for 1 hr, pulsed for 30 min with
      [3H]galactose and [14C]leucine, and chased for 2 hr; replicate experiments were
      conducted in which all media contained no TM or TM at 10 micrograms/ml.
      Tunicamycin significantly inhibited the incorporation of tritiated galactose into
      the tapeworm's carcass and 30,000-g tegumental membrane fraction. Incorporation
      of tritiated galactose into the tapeworm's tegumental surface membrane also was
      inhibited significantly when expressed relative to the incorporation of
      [14C]leucine. Tunicamycin did not affect the amounts of free, i.e., soluble,
      [3H]galactose or [14C]leucine recovered from the tapeworms not did it affect the
      short-term (2 min) uptake of [3H]galactose by tapeworms. Thus, the inhibitory
      effect of TM appears to be at the level of protein glycosylation rather than
      carbohydrate (galactose) transport. The data indicate that TM might be useful for
      producing tapeworm surface membranes with diminished carbohydrate moieties.

PMID- 9267393
TI  - Vitellogenin and ecdysteroid titers in Ixodes scapularis during vitellogenesis.
AB  - Ecdysteroids are the only hormones unequivocally identified thus far in ticks. We
      found a positive correlation between ecdysteroid concentration and vitellogenin
      synthesis in female Ixodes scapularis. Vitellogenin (Vg) synthetic activity was
      measured by an in vitro assay for Vg, involving incubations of the fat body with
      35S-methionine and immunoprecipitation collected on a solid-phase matrix, protein
      A. Vitellogenin synthetic activity in the fat body was undetectable in unfed
      females but was detected after tick attachment to the host. Vitellogenin
      production in the fat body remained low from attachment until 2 days prior to
      detachment from the host. Vitellogenin synthesis in the fat body peaked 2 days
      after detachment and declined to a level 2-3 times above background from 6 days
      after dropping from the host through oviposition. A peak of ecdysteroids in
      females 6 days after attachment preceded an increasing rate of Vg synthesis,
      suggesting a positive correlation between these parameters. Ecdysone and 20
      hydroxyecdysone, the 2 major ecdysteroids present during vitellogenesis, could
      not be detected in females prior to feeding or 2 days after attachment to the
      host; however, concentrations began to increase 4 days after attachment, peaked
      during rapid engorgement, and subsequently declined.

PMID- 9267394
TI  - Time lapse video microscopy and ultrastructure of penetrating sporozoites, types
      1 and 2 parasitophorous vacuoles, and the transformation of sporozoites to
      tachyzoites of the VEG strain of Toxoplasma gondii.
AB  - Videomicroscopy and transmission electron microscopy were used to study the
      interaction of Toxoplasma gondii sporozoites with cultured cardiopulmonary artery
      endothelial, embryonic bovine tracheal and Madin-Darby bovine kidney cells. No
      moving junction or exocytosis of rhoptries, micronemes, and dense granules was
      detected during the initial penetration of sporozoites into cultured cells,
      whereas constriction of the sporozoite and partial exocytosis of rhoptries
      occurred during movement of the sporozoite from the first parasitophorous vacuole
      (PV1) into the second vacuole (PV2). The PV1 was unusually large, lacked a
      tubulovesicular membrane network (TMN), and had an indistinct parasitophorous
      vacuolar membrane (PVM). Comparatively, the PV2 was small, had a distinct PVM,
      contained a well-developed TMN, and was surrounded by numerous host cell
      mitochondria. Sporozoites that passed completely through cells carried with them
      an envelope of host cell membranes and cytoplasm. Cultured cells occasionally
      endocytosed sporozoites that were enveloped by host cell material. After
      formation of the PV2, sporozoites replicated by endodyogeny to form tachyzoites.

PMID- 9267395
TI  - Parasitology meets ecology on its own terms: Margolis et al. revisited.
AB  - We consider 27 population and community terms used frequently by parasitologists
      when describing the ecology of parasites. We provide suggestions for various
      terms in an attempt to foster consistent use and to make terms used in parasite
      ecology easier to interpret for those who study free-living organisms. We suggest
      strongly that authors, whether they agree or disagree with us, provide complete
      and unambiguous definitions for all parameters of their studies.

PMID- 9267396
TI  - Evolutionary constraints on population structure: the parasites of Fundulus
      zebrinus (Pisces:Cyprinodontidae) in the South Platte River of Nebraska.
AB  - Population and community descriptor values (parasites per host, prevalence per
      parasite species, variance/mean ratios, species density, and diversity indices)
      for the 7-species parasite community of 61 relatively homogeneous samples of
      Fundulus zebrinus (Pisces: Cyprinodontidae) in the South Platte River of
      Nebraska, U.S.A., taken over a 14-yr period, are reported. South Platte River
      streamflow fluctuates over 2 orders of magnitude on several time scales-monthly,
      annually, and over multiple year wet-dry cycles. Relatively homogeneous sampling
      of a single host species with several parasite species provided a system that
      allowed assessment of the contribution of evolved parasite life cycles to
      population structure in an everchanging environment. No significant negative
      species-to-species associations were observed. Species abundance, order of
      abundance, and diversity were affected most strongly by streamflow, with high
      water reducing prevalence and abundance of larval trematode parasites. Each
      parasite species had its characteristic long- and short-term patterns of
      variation in population descriptor values, with mostly long-term stability
      superimposed on sometimes extreme short-term fluctuations of descriptor values.
      The differences in these characteristic patterns were considered products
      primarily of the evolved life cycle traits and transmission mechanisms operating
      in the common fluctuating environment. The parasite community as a whole showed
      resilience, returning to preperturbation diversity following extended periods of
      high water.

PMID- 9267398
TI  - Botfly (Diptera:Oestridae) parasitism of Ord's kangaroo rats (Dipodomys ordii) at
      Suffield National Wildlife Area, Alberta, Canada.
AB  - During field study of Ord's kangaroo rat (Dipodomys ordii) at Suffield National
      Wildlife Area, Alberta, Canada, a high prevalence of parasitism by botfly
      (Diptera: Oestridae) larvae was observed. Botflies have not previously been
      documented as parasites of kangaroo rats. Botfly parasitism could have a
      significant impact on the growth, survival, and reproduction of Ord's kangaroo
      rat, which is considered a vulnerable species in Canada. Therefore, it is
      important to investigate how botfly parasitism varies with season and with gender
      or age of host. In 1995, 525 individual kangaroo rats were caught by
      nightlighting and live trapping for a total of 952 capture records. Upon capture,
      each kangaroo rat was ear-tagged and thoroughly examined for parasites and
      wounds. Third-instar botfly (Cuterebra polita) larvae were observed in kangaroo
      rats between 16 June and 23 August. Prevalence was 34% based on 454 kangaroo rats
      sampled during that time, whereas the mean intensity was 2.3 larvae per infested
      host (n = 156, range = 1-11). In contrast to some other studies of botfly
      parasitism of rodents, there were no gender or age biases in either prevalence or
      intensity of infestation. The index of dispersion was 2.8, indicating that the
      parasites were aggregated in hosts. Botfly parasitism could be an important
      factor affecting northern populations of kangaroo rats; future investigations
      into the potential effects of botfly larvae on host fitness are warranted.

PMID- 9267397
TI  - Mixed-species Plasmodium infections of humans.
AB  - We analyzed point-prevalence data from 35 recent studies of human populations in
      which Plasmodium falciparum and one other Plasmodium species were the reported
      causes of malaria infections. For the P. falciparum-Plasmodium vivax pair, higher
      overall prevalence in a human population is associated with fewer mixed-species
      infections than expected on the basis of the product of individual species
      prevalences. This is not true for P. falciparum-Plasmodium malariae.

PMID- 9267400
TI  - A recombinant protein from Schistosoma mansoni useful for the detection of S.
      mansoni and Schistosoma haematobium antibodies.
AB  - A recombinant Schistosoma mansoni protein has been identified as a useful antigen
      for the detection of S. mansoni and Schistosoma haematobium antibodies. The
      purified recombinant protein, Sm22.3, was assayed using an enzyme-linked
      immunosorbent assay format against a battery of 491 well defined sera, including
      S. mansoni, S. haematobium, and Schistosoma japonicum infection sera, normal
      human sera, sera from 9 other parasitic infections, and sera from 2 additional
      infections. The sensitivity for detecting S. mansoni and S. haematobium
      infections with this single recombinant protein is 80.1%. The specificity is
      94.8%. However, 15 of the 16 cross-reactive sera are malaria infection sera, and
      we have data suggesting that these malaria sera are actually recognizing an
      epitope on the vector-derived 6Xhistidine tag of recombinant Sm22.3. If this is
      the case, then, the actual specificity of the assay is 99.6%.

PMID- 9267399
TI  - Study by ribosomal DNA ITS 2 sequencing and RAPD analysis on the systematics of
      four Metastrongylus species (Nematoda:Metastrongyloidea).
AB  - Four species of lungworms of the Metastrongylus genus are found sympatrically in
      the lungs of the wild boars (Sus scrofa L.) on the Chambord game reserve
      (France): Metastrongylus asymmetricus, M. confusus, M. pudendotectus, and M.
      salmi. These species are difficult to identify using morphological characters
      alone, and epidemiological evidence raises doubt about the existence of 4
      distinct species. Two molecular approaches (sequencing of ribosomal DNA Internal
      Transcribed Spacer 2 [ITS 2] and Random Amplified Polymorphic DNA assay [RAPD])
      were used to evaluate the genetic similarities between the 4 taxa. The ITS 2
      sequences of M. salmi and M. confusus were identical, whereas the sequences of
      the other species were distinct. On the other hand, RAPD analysis indicated
      unambiguously that the 4 species are genetically different. These results reveal
      the limitation of using only 1 molecular approach for taxonomic studies and
      indicate the need to examine different regions (ribosomal, mitochondrial DNA) in
      the genome of a species in complement with morphological and epidemiological
      data.

PMID- 9267401
TI  - Examination of extraintestinal tissue cysts of Isospora belli.
AB  - Relapse is common in immunocompetent and immunosuppressed humans infected with
      Isospora belli and is believed to be associated with the presence of
      extraintestinal stages. In the present study, we examined this important stage in
      an AIDS patient using histological, immunohistological, histochemical, and
      ultrastructural methods to better understand the development and structure of
      this stage and to develop better means of detecting infections. Antisera made in
      rabbits to Isospora suis, Toxoplasma gondii, Hammondia hammondi, Sarcocystis
      neurona, Neospora caninum, and Caryospora bigenetica were tested against I. belli
      tissue cysts in the avidin-biotin peroxidase complex (ABC) immunohistological
      test. Most antisera reacted positively in the ABC test at dilutions of 1:100 but
      not at dilutions of 1:250. Some antisera to N. caninum and H. hammondi reacted
      positively at dilutions of 1:1,000 in the ABC test. Most reactive antisera
      stained the tissue cyst wall and not the enclosed zoite. Eight histochemical
      tests were examined and most were nonreactive with I. belli zoites or tissue
      cysts. Transmission electron microscopy revealed that the tissue cyst wall was
      composed of granular material and was directly beneath the parasitophorous
      vacuole membrane. Zoites were in the center of the tissue cysts and were
      surrounded by fibrillar material that appeared to originate from the zoite
      surface. Tubulelike structures were present in the granular tissue cyst wall and
      in the fibrillar material that surrounded the zoite. Zoites contained a
      crystalloid body. New findings in the present study consisted of identifying what
      are probably early tissue cysts that lack a developed tissue cyst wall,
      demonstrating that more than 1 tissue cyst can occupy a host cell, describing the
      distribution of micronemes and the shedding of zoite membranes, and identifying
      tubular structures in the inner tissue cyst wall and inner compartment.

PMID- 9267402
TI  - Adoptive transfer of granulomatous inflammation to Brugia antigens in jirds.
AB  - Brugia pahangi infections of jirds (Meriones unguiculatus) produce a
      granulomatous inflammatory response within the lymphatic vessels. Granulomas that
      form around beads coated with soluble adult antigens embolized in the lungs have
      been used to measure this response. Similar lesions were observed in naive jirds
      receiving lymph node cells and splenocytes from animals with acute infections.
      This was not the case with cells from chronically infected jirds that were
      hyporesponsive to implanted antigen-coated beads. Passively transferred immune
      sera collected during the acute and chronic periods of infection did not transfer
      this response. Lymph node cells but not splenocytes obtained from chronically
      infected jirds induced a down regulation of this response in animals during the
      acute period. These results indicate that this inflammatory response in the jird
      is cell mediated and that adoptive transfer in jirds is feasible. The induction
      of the down-regulated state may also be mediated by cells, but not serum factors.

PMID- 9267403
TI  - Immunological characteristics and localization of the Trichinella spiralis
      glutathione S-transferase.
AB  - Trichinella spiralis glutathione S-transferase (TsGST) was isolated from crude
      extracts of L1 larvae by glutathione-affinity chromatography. Two closely
      migrating polypeptides with molecular masses of 28.5 and 28 kDa were identified
      by electrophoresis. Three isoforms of pI 5.6, 5.8, and 6.0 were detected by
      isoelectric focusing. Purified TsGST showed a low transferase activity as
      measured with 1-chloro-2,4-dinitrobenzene; glutathione peroxidase activity was
      also demonstrated using cumene hydroperoxide. A rabbit antiserum against TsGST
      reacted by western blot with crude extracts of Trichinella britovi and
      Trichinella nativa but not with extracts of Trichinella pseudospiralis, Fasciola
      hepatica, Schistosoma bovis, Schistosoma mansoni, Dirofilaria immitis, Toxocara
      canis, or Anisakis sp. TsGST was detected by western blot in extracts of T.
      spiralis adults, but not in newborn larvae or L1 excretory-secretory products;
      yet, an antiserum against T. spiralis excretory-secretory products reacted with
      TsGST. By immunoelectron microscopy, TsGST was found in the granules of the alpha
      and beta-stichocytes of L1 larvae, as well as in some granules of the
      stichocytes of 72-hr adults. Rabbits experimentally infected with T. spiralis
      developed substantial levels of anti-TsGST antibodies. Moreover, circulating
      TsGST was detected in serum by a sandwich-enzyme-linked immunosorbent assay,
      isolated from serum by glutathione-affinity chromatography, and characterized as
      TsGST by western blot.

PMID- 9267404
TI  - The effect of three distinct sex ratios at two Oesophagostomum dentatum worm
      population densities.
AB  - Helminth-free donor pigs were inoculated with infective larvae of Oesophagostomum
      dentatum. Five weeks later, the donor pigs were killed to recover the adult
      worms. By nonsurgical rectal transplantation, 6 groups of helminth-free recipient
      pigs were then given different female-to-male ratios (FMR) of O. dentatum worms
      (10% females [F], 50% F, 90% F) at either high (300 worms) or low (30 worms)
      doses. Fecal egg excretions were measured once weekly following transplantation
      until the pigs were killed 4 wk posttransplantation to assess the worm burdens
      and their location. There was a strong and significant correlation between
      numbers of male and female worms located in the different sections of the large
      intestine, suggesting that the worm sex as well as physiological factors in the
      pig intestine may govern the location of the worms. There were no significant
      differences in fecal egg counts or female worm fecundity between any of the
      groups. However at the low dose level, the female worm fecundity was markedly
      lower in the L10% F group than in the 2 other groups, thus suggesting for low
      worm densities an upper threshold for the FMR above which O. dentatum females
      produce fewer eggs.

PMID- 9267405
TI  - The distribution, prevalence, and morphological features of the cystic stage of
      an apicomplexan parasite of native littleneck clams (Protothaca staminea) in
      British Columbia.
AB  - Sixty-nine of 98 native littleneck clams (Protothaca staminea) collected from
      Cooper's Cove, Sooke Basin, British Columbia during November 1995 contained
      apicomplexan cysts. The cysts, which measured 20-150 microns in diameter occurred
      in several tissues, particularly in the kidney and in connective tissue
      surrounding the intestine and contained closely packed, banana-shaped zoites that
      measured about 25 x 4 microns. A pronounced fibrillar layer underlain by
      labyrinthine structures separated the host tissues from the cyst wall. The apical
      region of the zoites was reinforced and appeared as an electron-dense, caplike
      structure. The cysts probably represent a stage of a heteroxenous coccidian life
      cycle, with a predator of clams serving as the definitive host in which gamogony
      and sporogony occur.

PMID- 9267406
TI  - A protocol for the production of Neospora caninum tissue cysts in mice.
AB  - Identification of a definitive host for Neospora caninum has been inhibited by
      lack of an efficient method for producing bradyzoites, needed for oral
      infectivity trials. An improved protocol for producing bradyzoite-containing
      tissue cysts in mouse brains is described. Six variables, including mouse strain
      (Balb/C, CBA/Ca, and ICR), sex, N. caninum isolate (NC-2 and NC-Liverpool),
      tachyzoite inoculum dose, immunosuppression with methylprednisolone acetate
      (MPA), and sulfadiazine treatment were tested. Tissue cyst numbers were estimated
      using an immunohistologic staining procedure specific for bradyzoites. Male ICR
      mice (> or = 30 g) that were immunosuppressed with 2 mg MPA 7 days prior to and
      2.5 mg MPA at the time of subcutaneous inoculation with 400,000 N. caninum
      tachyzoites produced the highest numbers of tissue cysts. Significant numbers
      were produced by methods using the NC-2 strain of N. caninum; however, protocols
      using NC-Liverpool produced greater numbers of tissue cysts. Sulfadiazine
      treatment did not appear to contribute to tissue cyst production. The procedure
      described is superior to previously described methods with regard to numbers of
      tissue cysts produced, protocol reproducibility, and survival of mice until
      tissue cyst formation.

PMID- 9267407
TI  - Plasmodium yoelii sporozoite infectivity varies as a function of sporozoite loads
      in Anopheles stephensi mosquitoes.
AB  - Mechanisms by which Plasmodium sporozoites survive and maintain their infectivity
      within the salivary glands of mosquitoes are unknown. In this study we establish
      a relationship between the number of sporozoites present in the salivary glands
      of individual mosquitoes (sporozoite load) and sporozoite infectiousness (or
      "quality") as measured by infections in BALB/c or ICR mice. When Plasmodium
      yoelii-infected Anopheles stephensi mosquitoes were each allowed to feed on a
      single mouse, we noted that sporozoites from mosquitoes with higher sporozoite
      loads were more infectious in 13 of 30 (43%) mice. In a second experiment, we
      inoculated mice with known numbers of sporozoites from individual mosquitoes.
      Eleven of 18 (61%) and 16 of 18 (89%) mice that received 25 and 100 sporozoites,
      respectively, became infected. For inoculations using 100 sporozoites, again we
      noted that sporozoites from mosquitoes with higher sporozoite loads were more
      infectious to mice. In a third and final experiment, the overall infectiousness
      of sporozoites from individual mosquitoes was evaluated first by allowing
      individual mosquitoes to feed on individual mice and then by intravenous
      inoculations of 100 sporozoites in a second mouse. There was a significant
      difference in host infections as a function of sporozoite loads in 14 of 19 (74%)
      mice. Analysis of the feeding times for infected versus noninfected mosquitoes
      did not show a significant difference between the 2 groups. The mean total
      feeding times for 50 infected and 45 noninfected An. stephensi mosquitoes were
      306 (standard deviation [SD] = +/-230) and 441 (SD = +/-273) sec, respectively.
      Further, among infected An. stephensi mosquitoes there was no difference in
      probing times between cohorts that transmitted infectious sporozoites to mice and
      cohorts that failed to transmit infectious sporozoites. Our findings that
      sporozoite load influences sporozoite infectiousness or quality suggest that this
      may be an important factor in malaria parasite transmission.

PMID- 9267408
TI  - A proposed density-dependent model of long slender to short stumpy transformation
      in the African trypanosomes.
AB  - A simple arithmetic model is developed that is based upon the assumption: (1)
      that transformation of replicating long slender Trypanosoma brucei to
      nonreplicating short stumpy forms is parasite population density dependent; (2)
      that as the slender population increases there is a change in the external
      environment that triggers the slender to stumpy transformation; and (3) that
      stumpy forms of T. brucei do not induce the change in external environment that
      triggers slender to stumpy transformation or do so to a lesser extent than
      slender forms, thus preventing the proportion of stumpy forms in a population
      from reaching 100%. A simulation based on these assumptions shared many features
      with curves on numbers of long slender, intermediate, and short-stumpy forms of
      T. brucei during the first parasitemic wave of the 3 T. brucei subspecies in
      intact and immunosuppressed inbred mice.

PMID- 9267409
TI  - Myocardial G proteins in murine Chagas' disease.
AB  - G protein alpha subunits and their corresponding mRNA levels were determined in
      hearts obtained from mice infected with Trypanosoma cruzi, the etiologic agent of
      Chagas' disease. Protein and mRNA levels of the inhibitory G proteins G alpha i2
      and G alpha i3 were increased at 21 and 30 days postinfection (PI). After 60
      days, the abundance of protein and corresponding mRNA for G alpha i2 and G alpha
      i3 were no longer significantly different from uninfected mice. Twenty-one days
      after infection, G alpha s protein levels decreased markedly, but mRNA for the
      stimulatory protein did not change. Similar to the Gi proteins, by 60 days
      differences in G alpha s protein between infected and uninfected mice were no
      longer evident. There was an increase in the magnitude of G beta subunit protein
      21 and 30 days PI as compared with uninfected mice. However, 60 days PI the G
      beta subunit protein decreased to control levels. The close relationship between
      the infection-associated increase in G alpha i protein and mRNA suggests that
      control of protein expression is likely to be exerted at the transcription level.
      In contrast, control of infection-associated decrease in Gs appears to be at the
      translational level.

PMID- 9267410
TI  - Carbohydrate and LPG expression in Leishmania viannia subgenus.
AB  - Glycosylated molecules expressed on the cell surface of Leishmania promastigotes
      contribute to the outcome of contact between the parasite and its invertebrate
      and vertebrate hosts. The expression of several such molecules is growth phase
      dependent. Information on the expression of carbohydrates by Leishmania of the
      Viannia subgenus (braziliensis complex), a widespread cause of morbidity in the
      Americas, is fragmentary. We have examined the relationship between growth phase
      and the expression of glycosylated surface structures in WHO reference strains of
      3 species of the Viannia subgenus, i.e., L. panamensis, L. guyanensis, and L.
      braziliensis. Agglutination with lectins and the monoclonal antibody specific for
      the repeat unit of L. donovani lipophosphoglycan, CA7AE, distinguished
      logarithmic and stationary-phase promastigotes of all 3 species. Flow cytometry
      revealed increased heterogeneity and disparity in the expression of the repeat
      unit epitope in stationary-as compared to logarithmic-phase promastigotes.
      Biochemical analyses showed the LPG repeat unit of all 3 species reference
      strains to be constituted by mannose and galactose with little or no substitution
      and, hence, to be similar to the LPG of L. donovani. Initial quantitative
      analyses of L. braziliensis LPG indicated a 10-fold lower quantity of LPG in this
      species than L. donovani and an increase in the size of LPG in the stationary
      phase. These findings provide bases for isolating and biologically characterizing
      phenotypically distinct populations of promastigotes and for identifying
      molecular determinants of the host parasite-relationship among Leishmania
      Viannia.

PMID- 9267411
TI  - Pneumocystis carinii infection alters GTP-binding proteins in the lung.
AB  - The GTP-binding regulatory proteins (G proteins) in the membranes of the lung
      parenchyma from normal, uninfected ferrets were compared to those from
      immunosuppressed animals with and without Pneumocystis carinii pneumonitis. In
      lung membranes, pertussis toxin (PT) catalyzed ADP ribosylation of a 41-kDa
      protein; treatment with cholera toxin (CT) led to ribosylation of a 44-kDa
      polypeptide. Compared to that in the normal ferrets, the level of the 44-kDa
      protein was dramatically suppressed in the P. carinii-infected animals. Western
      blot analysis with specific antibodies to alpha s (which recognized CT
      substrates), alpha common (which reacted to PT substrates), the alpha q/11
      epitope, and the beta subunit demonstrated that these proteins were decreased in
      animals with P. carinii pneumonitis (PCP). Western blotting of PCP-free membranes
      with a pan-Ras antibody revealed a 21-kDa polypeptide (corresponding to small G
      proteins). The level of the 21-kDa protein in membranes from PCP-affected animals
      was only 30% of that in membranes from PCP-free animals. Finally, analogous
      studies performed with rat lung membranes revealed similar findings. These data
      suggest that, independent of its exacerbation of immunosuppression, PCP leads to
      extensive changes in the GTP-binding proteins in the lung.

PMID- 9267412
TI  - Electrophoretic separation and identification of phenoloxidases in hemolymph and
      midgut of adult Anopheles stephensi mosquitoes.
AB  - Anopheles mosquitoes frequently respond to invading malaria parasites with a
      rejection mechanism consisting of phenoloxidase-mediated melanization of
      ookinetes in the mosquito midgut epithelium. The relative roles of hemolymph vs.
      midgut phenoloxidase in this rejection mechanism is unclear. We have separated
      and identified phenoloxidase isozymes from midgut and hemolymph of Anopheles
      stephensi by native gel electrophoresis followed by zymography. The isozymes from
      the 2 sites had distinctively different electrophoretic characteristics.
      Hemolymph possessed 2 phenoloxidase-positive bands, both of which were
      bifunctional molecules that oxidized monophenol as well as o-diphenol substrates.
      Midgut extract possessed 3 bands that migrated more rapidly than those of the
      hemolymph. None of these midgut bands had detectable monophenoloxidase activity;
      they possessed, however, a broad spectrum of diphenoloxidase activity in their
      ability to oxidize both o- and p-diphenol substrates, as well as the laccase
      substrate syringaldazine. The 2 most rapidly migrating midgut PO bands could be
      distinguished from the more slowly migrating band through their insensitivity to
      inhibition by the chelating agent tropolone. A question to be resolved in the
      future relates to the relative roles of hemolymph vs. midgut phenoloxidase in
      mosquito defense against invasive parasites.

PMID- 9267413
TI  - Clinical, anatomic, and immunopathologic characterization of Babesia gibsoni
      infection in the domestic dog (Canis familiaris).
AB  - The pathology associated with acute, chronic, and recrudescent Babesia gibsoni
      infections was characterized in a group of 6 naturally or experimentally
      infected, spleen-intact and splenectomized dogs. All experimentally infected dogs
      became acutely parasitemic, lethargic, anemic, thrombocytopenic, and
      hemoglobinuric. Anatomic lesions associated, with the disease included diffuse
      nonsuppurative periportal and centrilobular hepatitis, multifocal necrotizing
      arteritis, membranoproliferative glomerulonephritis, reactive lymphadenopathy,
      diffuse erythrophagocytosis, and extramedullary hematopoiesis. The density of
      CD3+ lymphocytes within the liver sinusoids was markedly increased. Aggregates of
      large mononuclear cells with immunohistochemical features of activated
      macrophages were demonstrated in the central veins of the liver. Kupffer cells
      throughout the hepatic sinusoids appeared hypertrophic and prominent. The density
      of sinusoidal T lymphocytes, macrophages in central veins, and the degree of
      Kupffer cell hypertrophy were greatest in the splenectomized dogs. Multifocal
      deposits of IgM antibody were immunohistochemically demonstrated within the walls
      of inflamed arteries and renal glomeruli. The results of this study suggest that
      intense immunostimulation resulting in activation and expansion of T and B
      lymphocyte populations, macrophage recruitment and activation, vasculitis,
      glomerulonephritis and anemia contribute to the pathology associated with B.
      gibsoni infections.

PMID- 9267414
TI  - Two new species of Litomosoides (Nemata:Onchocercidae) from Ctenomys opimus
      (Rodentia:Ctenomyidae) on the altiplano of Bolivia.
AB  - Two filarioid nematodes, Litomosoides andersoni n. sp. and Litomosoides ctenomyos
      n. sp. (Nemata: Onchocercidae), are described from the mesenteries of the
      subterranean rodent Ctenomys opimus (Rodentia: Hystrichognathi) collected on the
      altiplano of Bolivia. Specimens collected near Rancho Huancaroma (Oruro Dept.) in
      1984 and 1986 can be recognized as undescribed by the structures of the spicules
      and stoma and the shape of the ovijector. This record represents the first time
      members of the genus Litomosoides have been recovered from rodents of the family
      Ctenomyidae; this also represents the first published report of these nematodes
      from mammals in Bolivia.

PMID- 9267415
TI  - Gongylonema madeleinensis N. sp. (Nematoda:Spiruroidea), from Mastomys
      erythroleucus (Rodentia) from a Senegalese island.
AB  - A new species of gongylonematid parasites of the rodent Mastomys erythroleucus is
      described. Gongylonema madeleinensis n. sp. differs from the other species of the
      genus by the size of its eggs and spicules-gubernaculum complex, the form and
      distribution of its cuticular scutella, and the absence of a pore on its cephalic
      plate. After examination of the esophageal content of 270 continental and 29
      insular rodents, G. madeleinensis n. sp. seems to be endemic to the island "des
      Madeleines" near Dakar, Senegal.

PMID- 9267416
TI  - Description of a new species of Maritrema (Digenea:Microphallidae) from Mar
      Chiquita coastal lagoon (Buenos Aires, Argentina) with notes on its life cycle.
AB  - Adults of Maritrema bonaerensis n. sp. (Digenea:Microphallidae) were collected
      from the intestine of the gulls Larus maculipennis and Larus atlanticus from Mar
      Chiquita coastal lagoon, Buenos Aires province, Argentina. The new species
      differs from M. pulcherrima Travassos, 1928 in having smaller sucker ratio,
      longer intestinal ceca, ovary not lobed, and larger eggs, and from Maritrema
      prosthometra Deblock and Heard, 1969 it differs in having larger suckers, smaller
      vitelline follicles, and in the absence of pars prostatica. It differs from
      Maritrema acadiae (Swales, 1933) in having larger body and pharynx and longer
      cirrus. It differs from Maritrema paracadiae Ching, 1974 in the larger pharynx,
      longer cirrus, and in the absence of prominent prostatic cells. From Maritrema
      majestova Ke, 1976, it differs in having a larger body, smaller eggs, and a long
      and protusible cirrus. Finally, M. bonaerensis differs from Maritrema chiricae
      Deblock, 1975 in the larger body, longer cirrus, and in the morphology of the
      seminal vesicle. Sporocysts and metacercarial stages isolated from the snail
      Heleobia australis australis and from the crabs Cyrtograpsus angulatus and
      Chasmagnatus granulata, respectively, suggest that those invertebrates could act
      as intermediate host in the life cycle of the new species in the lagoon. This
      assumption is supported by evidence derived from natural and experimental
      infections, from studies on biology of the actual and presumed hosts, as well as
      from previous reports on life cycles of species of Maritrema with similar
      transmission patterns.

PMID- 9267417
TI  - Analysis of Calliobothrium (Tetraphyllidea:Onchobothriidae) with descriptions of
      three new species and erection of a new genus.
AB  - Examination of voucher or type material, or both, of 9 of the 10 currently
      recognized species of Calliobothrium resulted in redescriptions of C. evani, C.
      lintoni, and C. pellucidum, and emendations of the descriptions of C. eschrichti
      and C. leuckarti. New collections of Calliobothrium from the spiral intestines of
      Mustelus spp. led to the discovery of 3 new species: Calliobothrium hayhowi n.
      sp. from Mustelus antarcticus in Australia, Calliobothrium riseri n sp. from
      Mustelus henlei in the Sea of Cortez, Mexico, and Calliobothrium violae n. sp.
      from Mustelus canis in the Northwestern Atlantic Ocean. New collections of C.
      evani from the Sea of Cortez established Mustelus lunulatus as a host for this
      species. Six species of Calliobothrium were examined with scanning electron
      microscopy. A cladistic analysis was performed on 12 of the 13 species of
      Calliobothrium recognized after the descriptions of the new taxa, using 34
      characters and 4 outgroup taxa. This analysis yielded a single most parsimonious
      tree with a consistency index of 0.68. This tree suggests that Calliobothrium is
      monophyletic only when the biloculated species Calliobothrium pritchardae is
      excluded from the genus. The new genus Biloculuncus is erected to house C.
      pritchardae so that the monophyly of Calliobothrium can be maintained. A key to
      the species of onchobothriids bearing 2 pairs of hooks per bothridium is
      presented.

PMID- 9267418
TI  - Description and epizootiology of Babesia poelea n. sp. in brown boobies (Sula
      leucogaster (Boddaert)) on Sand Island, Johnston Atoll, Central Pacific.
AB  - We describe a new species of piroplasm from brown boobies (Sula leucogaster) on
      Sand Island, Johnston Atoll National Wildlife Refuge, central Pacific. Mean
      parasitemia in adults and chicks was less than 1%, with the parasitemia in chicks
      significantly greater than in adults. There was no significant relation between
      the age of chicks and the degree of parasitemia. Parasitized red cells and red
      cell nuclei were significantly smaller than those of unparasitized cells, and
      infected birds appeared clinically normal. Prevalence of the parasite in chicks
      (54%) was significantly greater than in adults (13%), and the geographic
      distribution of parasitized chicks was skewed toward the eastern end of Sand
      Island. On the basis of morphologic characteristics, we named it Babesia poelea.
      The specific name is a concatenation of the Hawaiian names for dark (po'ele) and
      booby ('a). This is the second documentation of an endemic avian hemoparasite in
      seabirds from the central Pacific.

PMID- 9267419
TI  - Studies on a primaquine-tolerant strain of Plasmodium vivax from Brazil in Aotus
      and Saimiri monkeys.
AB  - A nonimmune American acquired an infection of Plasmodium vivax Type 1 malaria in
      Brazil in 1994. After returning to the U.S.A., he had a primary attack followed
      by 3 relapses. The primary attack and first 2 relapses were treated with a
      standard regimen of chloroquine, followed by 14 days of primaquine (15 mg/day).
      Following the third relapse, the primaquine treatment was extended to 28 days. No
      further relapses occurred. The lack of response to primaquine by this strain may
      recommend it as a suitable candidate for chemotherapeutic study if it can be
      adapted to an animal model. Anopheles quadrimaculatus mosquitoes infected by
      feeding on the patient during the first relapse were used to establish the strain
      in Aotus and Saimiri monkeys. Monkeys supported well the development of long
      lasting parasitemia. Anopheles freeborni, Anopheles stephensi, and Anopheles
      gambiae mosquitoes were readily infected by feeding on the monkeys and by
      membrane feeding on diluted blood. Monkey-to-monkey transmission was obtained via
      the bites of infected mosquitoes and the intravenous injection of sporozoites
      dissected from salivary glands. This parasite is designated as the Brazil I/CDC
      strain of P. vivax.

PMID- 9267420
TI  - Oral administration of putrescine inhibits Cryptosporidium parvum infection of
      neonatal C57BL-6 mice and is independent of nitric oxide synthesis.
AB  - We examined the efficacy of oral administration of putrescine (a byproduct of
      arginine metabolism) in the prevention of Cryptosporidium parvum infection of
      neonatal C57BL-6 mice. Mice were challenged with the parasite at 7 days of age.
      Mice receiving putrescine from 3 through 10 days of age had a delayed pattern of
      infection as compared with control mice. Mice receiving putrescine from 3 through
      21 days of age did not become infected, whereas control mice were heavily
      infected. We also tested the hypothesis that putrescine inhibited C. parvum
      infection by enhancing nitric oxide (NO) production. Mice receiving the NO
      inhibitor N omega-L-arginine methyl ester (L-NAME) parenterally and putrescine
      orally did not become infected. Thus, it appears that putrescine inhibits C.
      parvum infection in an NO-independent manner.

PMID- 9267421
TI  - First record of Pachysentis canicola (Acanthocephala:Oligacanthorhynchida) and
      the occurrence of Mesocestoides sp. tetrathyridia (Cestoidea:Cyclophyllidea) in
      the western diamondback rattlesnake, Crotalus atrox (Serpentes:Viperidae).
AB  - This paper represents the first documentation and description of Pachysentis
      canicola cystacanths and the first report of a Pachysentis sp. in a paratenic
      reptile from the Americas. The western diamondback rattlesnake (Crotalus atrox)
      is also listed as a new host for tetrathyridia of the cyclophyllidean cestode
      (Mesocestoides sp.) and for the cystacanths of the oligacanthoryhynchid
      acanthocephalan (P. canicola). Six rattlesnake specimens were examined from Nolan
      County (32.30 degrees N, 100.39 degrees W), Texas. Four snakes (67%) were found
      parasitized with between 3 and 16 (mean 7) encapsulated tetrathyridia and 1 host
      additionally was infected with 6 P. canicola cystacanths within its mesentery.

PMID- 9267422
TI  - Partially degraded DNA of parasitological interest serves as an adequate template
      for the production of random amplified polymorphic DNAs (RAPDs).
AB  - Genomic DNA was extracted from Schistosoma mansoni adult worms and deliberately
      degraded by sonication. Samples with varying average molecular weight were
      subjected to RAPD (randomly amplified polymorphic DNA) analysis using the primer
      3307 (5'-AGTGCTACGT-3') and other primers. Reproducible and complex DNA banding
      patterns were obtained, irrespective of the extent of DNA degradation. The same
      amplification protocol was employed with naturally degraded Biomphalaria glabrata
      genomic DNA and the primer 3302 (5'-CTGATGCTAC-3'). Again, reproducible RAPD
      patterns resulted. The experiment shows that the partially degraded DNA samples
      can be safely compared in RAPD analysis without artifactual bands compromising
      the accuracy of genetic analysis. Thus RAPD analysis permits complex and
      reproducible DNA fingerprinting from degraded samples of parasitological
      interest.

PMID- 9267423
TI  - Distribution of tissue cysts in organs of rats fed Toxoplasma gondii oocysts.
AB  - Toxoplasma gondii-infected rats are considered important in the epidemiology of
      toxoplasmosis because they can serve as a source of infection for pigs and
      possibly for cats. To study the distribution of tissue cysts, 10 Sprague-Dawley
      female adult rats were fed 1 oocyst (3 rats, group A) or 10(5) oocysts (3 rats,
      group B) of the VEG strain or 10(4) oocysts of the GT-1 strain (4 rats, group C)
      of T. gondii. All rats in a group were killed at 1 time: 76 (group A), 240 (group
      B), and 443 (group C) days after oocyst inoculation (DAI). Tissue cysts were seen
      in the brains of all 10 rats by direct microscopic examination. Portions or whole
      organs from heart, lung, liver, spleen, small intestines, kidneys, skeletal
      muscle, eyes, mesenteric lymph nodes, stomach uterus, and tongue from all rats in
      a group were pooled by organ, digested in acid-pepsin solution for 60 min, washed
      in saline, and then bioassayed in mice. Based on bioassay in mice, tissue cysts
      were present in 3 extraneural tissues of rats from group A, 6 extraneural organs
      of group B, and in 10 extraneural organs of rats of group C. Tissue cysts were
      present in skeletal muscles and kidneys of all 3 groups. Thus, tissue cysts are
      formed both in neural and extraneural tissues of rats. Therefore portions of
      infected rats, excluding the head, can be a source of infection for pigs and
      cats.

PMID- 9267424
TI  - Amebicidal activity of wild animal serum.
AB  - The sera of 16 species of wild animals representing 5 classes of vertebrates were
      assayed for amebicidal activity against species of Naegleria. The greatest
      activity was observed for sera of bullfrogs, muskrats, and raccoons, all of which
      are animals associated with water. In contrast, the sera from animals such as
      toads, box turtles, sparrows, and squirrels exhibited minimal or no amebicidal
      activity. In general, pathogenic Naegleria tended to be less susceptible than
      nonpathogenic Naegleria to the lytic effect of raccoon serum. Heat-inactivated
      serum was not amebicidal, suggesting that perhaps complement may be involved in
      the serum-mediated lysis of amebas.

PMID- 9267425
TI  - Localization of cytochrome oxidase and the 2-methyl branched-chain enoyl CoA
      reductase in muscle and hypodermis of Ascaris suum larvae and adults.
AB  - Rabbit lung-derived third-stage larvae (L3) of Ascaris suum are aerobic and
      cyanide sensitive but also contain many enzymes specific to anaerobic pathways.
      To localize these enzymes, diaminobenzidine (DAB) staining for cytochrome oxidase
      (COX) and immunogold labeling for 2-methylbutyryl enoyl CoA reductase (ECR) were
      performed on sections of hypodermis and muscle of adults and larvae of A. suum
      and visualized by transmission electron microscopy. As predicted, adult
      hypodermal and muscle mitochondria did not exhibit COX staining; however,
      hypodermal and muscle mitochondria of the L3 and fourth-stage larvae (L4) were
      DAB positive. In contrast, hypodermal mitochondria from the adult, L3, and L4 did
      not exhibit ECR immunoreactivity, whereas mitochondria from muscle of all 3 were
      ECR positive. These observations suggest that both the ECR and COX are
      colocalized in muscle mitochondria of the L3.

PMID- 9267426
TI  - Alteration in brain metabolites of jirds infected with alveolar Echinococcus.
AB  - The Meriones unguiculatus-Echinococcus multilocularis host-parasite system was
      used to evaluate changes in metabolite levels in the brain of the infected host.
      Nuclear magnetic resonance analysis of perchloric acid extracts of the entire
      brain of jirds revealed that infection caused a change in the concentration of
      several metabolites, especially those that serve as amino acidergic
      neurotransmitters in this organ. The concentrations of the neuroexcitatory
      compounds glutamate and aspartate and the neuroinhibitory compounds glycine and
      taurine were significantly reduced. Those of 2 other amino acids, glutamine and
      alanine, were also decreased. In addition, concentrations of
      glycerophosphocholine and phosphocholine were also lower, whereas those of
      phosphocreatine and N-acetylaspartate were elevated.

PMID- 9267427
TI  - Ixodid ticks infesting rodents and sheep in diverse biotopes of southern India.
AB  - A total of 127 rodents were trapped in southern India. Examination of these
      rodents revealed the presence of 2 species of ticks, Haemaphysalis spinigera and
      Rhipicephalus ramachandrai. The former species is the principal vector of
      Kyasanur Forest Disease (KFD) in India, and the latter's role, if any, is
      unknown. Sheep grazing in 1 of the study area were infested with another ixodid
      tick. Haemaphysalis intermedia, which is a vector of Bhanja virus in India. The
      presence of H. spinigera on domestic rats is important from the standpoint of KFD
      enzootiology. This tick shows a narrow habitat preference but a wide host range.
      In peridomestic situations, the field rodent Bandicota bengalensis did not harbor
      any tick species. Contiguity of feral and domestic biotopes in some areas
      contributed to the transfer of R. ramachandrai from its preferred wild rodent
      host, Tatera indica, to domestic rats Rattus sp.

PMID- 9267428
TI  - Dermatitis in young Florida sandhill cranes (Grus canadensis pratensis) due to
      infestation by the chigger, Blankaartia sinnamaryi.

PMID- 9267429
TI  - Antagonistic effect of human alpha-1-antitrypsin on excystation of
      Cryptosporidium parvum oocysts.
AB  - This study evaluated the effects of the human serine protease inhibitor alpha-1
      antitrypsin (AAT) on in vitro excystation and infectivity of Cryptosporidium
      parvum. Excystation was monitored at 37 C in RPMI medium in the presence of 0,
      100, 500, or 1,000 micrograms/ml AAT. AAT significantly inhibited (P < 0.05)
      excystation of bleach-decontaminated oocysts in a concentration-dependent manner
      at incubation intervals from 15 to 90 min but did not alter the excystation
      dynamics of unbleached oocysts. Bleach-treated oocysts, suspended in RPMI
      containing 0, 1, 10, 100, 500, or 1,000 micrograms/ml AAT, were used to inoculate
      bovine fallopian tube epithelial (BFTE) cell monolayers. Alternately,
      sporozoites, excysted at 37 degrees C and collected by filtration, were used to
      inoculate BFTE cells under the same conditions. The mean number of parasites
      counted in AAT-treated, oocyst-inoculated cells was significantly less (P < 0.01)
      than control mean values at 24 and 48 hr post-inoculation (PI); longer PI
      intervals (72-96 hr) exhibited a decreased inhibitory effect. AAT did not inhibit
      parasite infection when cultures were inoculated with C. parvum sporozoites. The
      findings of this study show that the anticryptosporidial potential of AAT is
      primarily associated with an antagonistic effect on oocyst excystation.

PMID- 9267431
TI  - Differential expression of two functional serine/threonine protein kinases from
      soybean that have an unusual acidic domain at the carboxy terminus.
AB  - Two soybean cDNA clones, SPK-3 and SPK-4, encoding putative protein kinases were
      isolated and characterized. Both cDNAs encoded approximately 40-kDa
      serine/threonine kinases with unusual stretches of acidic amino acids in their
      carboxy-terminal regions, which are highly homologous to PKABA1 from wheat and
      ASKs from Arabidopsis. These kinases are encoded by one- or two-copy genes in the
      soybean genome. Notably, SPK-3 and -4 showed different patterns of expression in
      various soybean tissues. SPK-3 is highly expressed in dividing and elongating
      tissues of young seedlings but relatively weakly in tissues of mature plants. In
      contrast, SPK-4 showed relatively high and constitutive expression in all the
      tissues examined except for leaf tissues of mature plants. Although various
      stressors, such as dehydration and high salinity, increased the expression of
      both genes, the induction kinetics were different. The two genes also differed in
      their response to abscisic acid (ABA). SPK-3 was induced but SPK-4 was not
      affected by exogenously supplied abscisic acid. In accordance with these
      expression data analysis of the activity of a chimeric SPK-3 promoter::beta
      glucuronidase (GUS) reporter gene by transient expression in tobacco leaves
      confirmed the inducibility of SPK-3 by salt and ABA. Polyclonal antibodies raised
      against a recombinant SPK-4 protein produced in Escherichia coli specifically
      recognized both recombinant SPK-3 and -4 proteins. Kinase assays using affinity
      purified SPK-4/ antibody complexes with crude soybean extracts as substrate
      identified specific phosphorylation of two 41 and 170 kDa soybean proteins that
      were phosphorylated on serine residues. Taken together, our results suggest that
      SPK-3, and/or SPK-4 are functional serine protein kinase(s). Furthermore, SPK-3
      and -4 may play different roles in the transduction of various environmental
      stresses.

PMID- 9267430
TI  - Silencing of waxy genes in rice containing Wx transgenes.
AB  - In order to study gene silencing in a monocot system we introduced a waxy (Wx)
      gene into rice. In the pollen grain of the transgenic wild-type plants, two types
      of Wx gene silencing were observed: Type I in which all the pollen grains showed
      the mutant (wx) phenotype, and Type II in which 50% of the pollen grains showed
      the wx phenotype. Analysis of Wx gene expression in the progeny of selfing and
      outcrossing indicated that Wx gene silencing was meiotically transmitted to the
      offspring. The number of transgene copies and transgene loci was determined by
      Southern blot analysis and suggested that the Wx transgene may have a
      paramutagenic effect on the endogenous Wx genes. In contrast to the pollen grain,
      the wx phenotype was not observed in the endosperm. However, the level of WAXY
      (WX) protein in the endosperm of Type I lines was similar to that in non
      transgenic seed, while in Type II lines two classes of seeds, showing high and
      low levels of the protein segregated. When the same transgene was introduced into
      wx mutants in which no Wx transcript was detectable, the transgene behaved as a
      dominant Mendelian factor and no silencing was found, suggesting that the
      activity of the endogenous Wx gene influences the silencing phenomenon. Our study
      of Wx gene silencing in rice extends the well-known phenomenon of gene silencing,
      so far observed mainly in dicots, to a cereal.

PMID- 9267432
TI  - Regulation by tetracycline of gene expression in Saccharomyces cerevisiae.
AB  - A convenient system for the control of gene expression in Saccharomyces
      cerevisiae was developed. Tetracycline-responsive promoters were constructed by
      fusing the tetracycline operator (tetO) to the S. cerevisiae HOP1 promoter. When
      fused to the tetracycline repressor (tetR), trans-activation domains of both GAL4
      and HAP4 were capable of promoting transcription from the tetO-HOP1 chimeric
      promoter, but the tetR-HAP4 fusion activator was the more efficient
      transcriptional activator. Addition of tetracycline nearly completely repressed
      activator-dependent transcription from the tetO-HOP1 promoter. Moreover,
      tetracycline-dependent repression of YEF3, CDC28 and RAM2 expression impaired
      cell growth. Thus, this system is useful for the elucidation of gene function in
      S. cerevisiae.

PMID- 9267433
TI  - Effects of starvation for heme on the synthesis of porphyrins in Escherichia
      coli.
AB  - A study is described of the regulation of porphyrin synthesis in Escherichia coli
      using a heme-permeable, hemH deletion mutant, designated VS212. This strain
      utilizes only exogenous hemin that is supplied in the medium and accumulates
      porphyrins since the final step in the synthesis of heme is genetically blocked.
      It is possible, therefore, to monitor the rate of synthesis of heme by examining
      the accumulation of porphyrins. Using this system, we found that the rate of
      production of porphyrins depended on the availability of heme. The lower the
      concentration of hemin in the medium, the higher the level of porphyrins that
      accumulated. We next examined the mechanism responsible for the activation of
      porphyrin synthesis upon starvation for heme. The main activation occurred at the
      step that leads to the synthesis of 5-aminolevulinic acid (ALA). Starvation for
      heme induced the expression of a hemA-lacZ fusion gene, as previously reported,
      but an activation pathway that is independent of the hemA promoter was also
      identified. We found that starvation for heme caused the stringent response, and
      such starvation promoted the synthesis of porphyrins without having any effect on
      the expression of the hemA-lacZ fusion gene. We suggest a model for the
      regulation of porphyrin synthesis whereby the synthesis of porphyrins is
      coordinated with that of proteins.

PMID- 9267434
TI  - Molecular cloning and characterization of cDNAs for anionic and neutral
      peroxidases from suspension-cultured-cells of sweet potato and their differential
      expression in response to stress.
AB  - Two peroxidase (POD) cDNAs, swpal and swpn1, were isolated and characterized from
      suspension-cultured cells of sweet potato in order to understand the
      physiological function of POD isozymes. Sequence analysis showed that swpa1
      encoded an anionic POD and swpn1 encoded a neutral POD. The swpa1 and swpn1 genes
      were both highly expressed in suspension-cultured cells in accordance with the
      high POD activity of these cells. Although both gene transcripts were detected in
      the stems of intact plants, their transcription levels were much lower than in
      suspension-cultured cells. During cell growth the pattern of mRNA accumulation of
      swpa1 differed from that of swpn1, suggesting that expression of these genes is
      differentially regulated by cell growth stage. In addition, the swpa1 and swpn1
      genes responded differently to oxidative stress induced by chilling. The
      expression of swpa1 was weakly induced by 15 degrees C acclimation and strongly
      induced by 4 degrees C chilling, whereas the mRNA level of swpn1 was increased by
      15 degrees C acclimation and reduced by 4 degrees chilling. This indicates that
      the two isozymes encoded by swpa1 and swpn1 might contribute to protection
      against cold-induced oxidative stress through different signaling pathways. In
      leaves, both genes were induced by wounding with broadly similar expression.
      patterns. Genomic analysis suggests that the two isozymes are encoded by
      different loci in the sweet potato genome.

PMID- 9267435
TI  - A suicide vector for allelic recombination involving the gene for glutamate 1
      semialdehyde aminotransferase in the cyanobacterium Synechococcus PCC 7942.
AB  - Gabaculine (2,3-dihydro 3-amino benzoic acid) is a potent inhibitor of
      tetrapyrrole biosynthesis in organisms that use the C5 pathway for the synthesis
      of delta-aminolaevulinic acid. Glutamate semialdehyde aminotransferase (GSA-AT),
      the enzyme catalysing the formation of this key precursor of tetrapyrroles, is
      normally inhibited by concentrations of gabaculine in the order of 5 microM.
      However, in Synechococcus 6301 strain GR6, a cyanobacterium that is resistant to
      100 microM gabaculine, this enzyme has undergone two changes in structure: a
      deletion of three amino acids from positions 5 to 7 and the substitution of
      isoleucine for methionine at position 248. To establish the effect in vivo of
      these specific changes in the gene for GSA-AT (hemL), a suicide vector (pHS7)
      containing an antibiotic cassette was constructed to achieve the replacement, by
      homologous recombination, of the wild-type hemL gene in the chromosome by a
      modified form of the gene. Recombinant strains of Synechococcus 7942 obtained
      using pHS7-hemLGR6 were indistinguishable from Synechococcus 6301 GR6 in terms of
      the resistance of growth and of chlorophyll accumulation to high concentrations
      of gabaculine, while a wild-type recombinant produced using pHS7-hemLWT had
      retained its sensitivity. Southern hybridisation using gene probes for hemL, ampr
      and cmr confirmed that chromosomal integration of the plasmids had occurred in
      both WT and GR6 recombinants. Growth and chlorophyll accumulation in equivalent
      strains with the hemL gene containing either the deletion or the transition
      characteristic of Synechococcus 6301 GR6 were inhibited by 10 microM gabaculine.
      Consequently, resistance in vivo to high concentrations of this compound is
      dependent on both the changes in gene/enzyme structure. This investigation has
      established the effectiveness of the suicide vector pHS7 for studying the effect
      in vivo of specific changes in the hemL gene. It has also demonstrated that
      replacement of the wild-type gene by that from Synechococcus 6301 GR6 is
      sufficient to confer resistance in vivo to high concentrations of gabaculine.

PMID- 9267436
TI  - The MBR1 gene from Saccharomyces cerevisiae is activated by and required for
      growth under sub-optimal conditions.
AB  - The MBR1 gene was isolated as a multicopy suppressor of the phenotype on glycerol
      medium of a Saccharomyces cerevisiae strain mutant for the Hap2/3/4/5
      transactivator complex. In this paper, we show that Mbr1p is a limiting factor
      for growth on glycerol medium under the following sub-optimal culture conditions:
      in late growth phase, at low temperature, at high external pH or in the presence
      of 1,10-phenanthroline. Moreover, deletion of MBR1 protects cells against stress,
      whilst overexpression of this gene has the opposite effect. MBR1 expression is
      induced in the late growth phase and is negatively controlled by the cAMP
      dependent protein kinase A (PKA). Both activation of PKA or overexpression of
      SOK1 or SCH9-two genes isolated as multicopy suppressors of a PKA null mutant
      suppress the mbr1 growth defect. Our results indicate that Mbr1p is not an
      essential element of any one of these pathways. Deletion of SAC1, a gene
      implicated in vesicular transport, in association with MBR1 deletion, causes
      synthetic lethality. A possible role of Mbr1p in intracellular trafficking is
      discussed.

PMID- 9267438
TI  - Mutational analysis of the Streptomyces lividans recA gene suggests that only
      mutants with residual activity remain viable.
AB  - Temperature-sensitive integration plasmids carrying internal fragments of the
      Streptomyces lividans TK24 recA gene were constructed and used to inactivate the
      chromosomal recA gene of S. lividans by gene disruption and gene replacement.
      Integration of these plasmids resulted in recA mutants expressing C-terminally
      truncated RecA proteins, as deduced from Southern hybridization experiments.
      Mutants FRECD2 in which the last 42 amino acids, comprising the variable part of
      bacterial RecA proteins, had been deleted retained the wild-type phenotype. The
      S. lividans recA mutant FRECD3 produced a RecA protein lacking 87 amino acids
      probably including the interfilament contact site. FRECD3 was more sensitive to
      UV and MMS than the wild-type. Its ability to undergo homologous recombination
      was impaired, but not completely abolished. Integration of the disruption plasmid
      pFRECD3 in S. coelicolor "Muller" caused the same mutant phenotype as S. lividans
      FRECD3. In spite of many attempts no S. lividans recA mutants with deletions of
      165 C-terminal amino acids or more were isolated. Furthermore, the recA gene
      could not be replaced by a kanamycin resistance cassette. These experiments
      indicate a crucial role of the recA gene in ensuring viability of Streptomyces.

PMID- 9267437
TI  - Examination of the intron in the meiosis-specific recombination gene REC114 in
      Saccharomyces.
AB  - REC114 is one of 10 genes known to be required for the initiation of meiotic
      recombination in Saccharomyces cerevisiae. It is transcribed only in meiosis, and
      our previous sequence analysis suggested the presence of an intron in the 3' end
      of the gene. Hypotheses in the literature have suggested, because of its unusual
      location, either that the putative intron in REC114 is likely to be necessary for
      expression, or that there may actually be no intron present. This work
      demonstrates that REC114 does have an intron and is one of only three genes in
      yeast with introns located in the 3' end. Furthermore, the 3' splice site
      utilized in REC114 is a very rare AAG sequence; only three other genes in yeast
      use this nonconsensus sequence. The splicing of REC114 does not require MER1, a
      gene known to be involved in meiosis-specific RNA processing. In fact, an
      intronless copy of REC114 can complement a null rec114 mutation. Thus, it does
      not appear that the intron is essential for expression of REC114. Although the
      intron is not absolutely required for meiotic function, it is conserved in
      evolution; two other species of yeast contain an intron at the same location in
      their REC114 genes.

PMID- 9267440
TI  - Use of allele specificity of comigrating AFLP markers to align genetic maps from
      different potato genotypes.
AB  - The allele specificity of AFLP markers was assessed in five relatively unrelated
      potato genotypes. To this end, two diploid mapping populations of potato, F1SH x
      RH and F1AM x RH, were analysed using four and six AFLP primer combinations,
      respectively, recently applied to the analysis of the genetically well
      characterized backcross population BC_C x E. The AFLP profiles of the five
      parents revealed 733 AFLP markers and, when identical primer combinations were
      used, 131 comigrating AFLP markers were identified. After construction of five
      parental maps, the genomic positions of these comigrating AFLP markers were
      compared and 117 markers (89%) which targeted the same genomic region were
      assumed to be homologous. Of these putative homologues, 20 markers, each cloned
      from at least two genotypes, were sequenced and 19 sets of amplification products
      were shown to be nearly identical. The number of AFLP markers previously mapped
      in population BC_C x E ranged from three to eleven per chromosome, which allowed
      a reliable assessment of chromosome numbers from individual linkage groups
      obtained in populations F1SH x RH and F1AM x RH. The high incidence of
      corresponding AFLP alleles was confirmed by using an additional set of five
      primer combinations. The 733 AFLP markers localized provide a valuable reference
      collection for future mapping studies in potato. As a consequence AFLP analysis
      may replace more laborious locus-specific marker techniques.

PMID- 9267439
TI  - Isolation and characterization of the krev-1 gene, a novel member of ras
      superfamily in Neurospora crassa: involvement in sexual cycle progression.
AB  - Genes belonging to the ras superfamily encode low-molecular-weight GTP/GDP
      binding proteins that are highly conserved in wide variety of organisms. We used
      the polymerase chain reaction (PCR) to isolate a novel member of the ras
      superfamily from the filamentous fungus Neurospora crassa and obtained a
      mammalian Krev-1 homolog. We named the gene krev-1 and analyzed its structure and
      function. The krev-1 gene encodes a polypeptide of 225 amino acids, which is
      nearly 60% homologous to the mammalian Krev-1 p21. The krev-1 gene product
      (KREV1) is functionally analogous to mammalian Krev-1 p21 and Rsr1p/Bud1p, a Krev
      1 homolog from the yeast Saccharomyces cerevisiae. GAL1-driven expression of
      KREV1 in a wild-type yeast strain resulted in a random budding pattern, as did
      its mammalian counterpart Krev-1 p21. We disrupted the krev-1 gene by RIP (repeat
      induced point mutation), but the krev-1 disruptants showed no abnormalities. By
      in vitro mutagenesis, we constructed several mutant krev-1 genes (G21V, A68T, and
      D128A) which mimic constitutively active mutants of Ha-ras, and the krev-1 (K25N)
      mutant which is analogous to a dominant-negative mutant of Ha-ras. Each mutant
      gene was introduced into the wild-type strain and the phenotypes were analyzed.
      We could not observe any difference in vegetative growth between these
      transformants. When each strain was used as the female in mating tests, the
      development of perithecia from protoperithecia was inhibited in all cases. The
      results indicate that the krev-1 gene may be involved in sexual cycle
      progression.

PMID- 9267441
TI  - NIH Consensus Statement. Breast cancer screening for women ages 40-49.
AB  - OBJECTIVE: To provide health care providers, patients, and the general public
      with a responsible assessment of currently available data regarding the
      effectiveness of mammography screening for women ages 40-49. PARTICIPANTS: A non
      Federal, nonadvocate, 12-member panel representing the fields of oncology,
      radiology, obstetrics and gynecology, geriatrics, public health, and epidemiology
      and including patient representatives. In addition, 32 experts in oncology,
      surgical oncology, radiology, public health, and epidemiology presented data to
      the panel and to a conference audience of 1,100. EVIDENCE: The literature was
      searched through Medline and an extensive bibliography of references was provided
      to the panel and the conference audience. Experts prepared abstracts with
      relevant citations from the literature. Scientific evidence was given precedence
      over clinical anecdotal experience. CONSENSUS PROCESS: The panel, answering
      predefined questions, developed its conclusions based on the scientific evidence
      presented in open forum and the scientific literature. The panel composed a draft
      statement that was read in its entirety and circulated to the experts and the
      audience for comment. Thereafter, the panel resolved conflicting recommendations
      and released a revised draft statement at the end of the conference. The final
      statement with a minority report was completed within several weeks after the
      conference. CONCLUSIONS: The Panel concludes that the data currently available do
      not warrant a universal recommendation for mammography for all women in their
      forties. Each woman should decide for herself whether to undergo mammography. Her
      decision may be based not only on an objective analysis of the scientific
      evidence and consideration of her individual medical history, but also on how she
      perceives and weighs each potential risk and benefit, the values she places on
      each, and how she deals with uncertainty. However, it is not sufficient just to
      advise a woman to make her own decision about mammograms. Given both the
      importance and the complexity of the issues involved in assessing the evidence, a
      woman should have access to the best possible relevant information regarding both
      benefits and risks, presented in an understandable and usable form. Information
      should be developed for women in their forties regarding potential benefits and
      risks to be provided to enable each woman to make the most appropriate decision.
      In addition, educational material to accompany this information should be
      prepared that will lead women step by step through the process of using such
      information in the best possible way for reaching a decision. For women in their
      forties who choose to have mammography performed, the costs of the mammograms
      should be reimbursed by third-party payors or covered by health maintenance
      organizations so that financial impediments will not influence a woman's
      decision. Additionally, a woman's health care provider must be equipped with
      sufficient information to facilitate her decisionmaking process. Therefore,
      educational material for physicians should be developed to assist them in
      providing the guidance and support needed by the women in their care who are
      making difficult decisions regarding mammography. The two panel members writing a
      minority report believed the risks of mammography to be overemphasized by the
      majority and concluded that the data did support a recommendation for mammography
      screening for all women in this age group and that the survival benefit and
      diagnosis at an earlier stage outweigh the potential risks.

PMID- 9267442
TI  - Synopsis book. Best articles relevant to pediatric allergy and immunology. 1995
      1996.

PMID- 9267443
TI  - Detection and tissue distribution of potato spindle tuber viroid in infected
      tomato plants by tissue print hybridization.
AB  - Potato spindle tuber viroid (PSTVd) was detected in two cultivars of tomato
      (Lycopersicon esculentum Mill.) by tissue print hybridization of cross-sections
      of stem and rhachis, using a 35S-labeled PSTVd RNA probe. PSTVd was detectable in
      the viroid-sensitive and symptom-developing cv "Rutgers" 2 weeks p.i., and in the
      viroid-tolerant and practically symptomless cv "Goldkugel" 3 weeks p.i. In both
      tomato cultivars, PSTVd accumulated in the upper parts of the plants newly grown
      after inoculation. It was predominantly found in association with the ring formed
      by the vascular tissue. The final accumulation of PSTVd as well as its spatial
      distribution were similar in the sensitive and in the tolerant tomato cultivar,
      as estimated from the tissue print autoradiographs. Thus, tissue print
      hybridization provides a rapid and sensitive means for viroid diagnosis and for
      the assessment of tissue-specific localization of the viroid RNA.

PMID- 9267444
TI  - A sensitive PCR assay system for the quantitation of viral genome equivalents:
      human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV).
AB  - A sensitive and reliable quantitative method based on the polymerase chain
      reaction (PCR) and the reverse transcription polymerase chain reaction (RT-PCR)
      to detect and quantify human immunodeficiency virus (HIV-1) and hepatitis B virus
      (HBV), respectively, was developed. The samples are co-processed together with
      two internal standards (calibrators). The amplicons are separated on denaturing
      polyacrylamide gels and co-detected and quantitated by laser induced
      fluorescence. HIV-1 and HBV containing biological samples, including samples from
      international test panels, were accurately quantitated. The procedure has proven
      to be a valuable tool in the quality control of biologicals such as plasma
      products and may serve to monitor disease progression and response to antiviral
      therapy.

PMID- 9267445
TI  - Hydropathic characteristics of adenovirus hexons.
AB  - The complete nucleotide sequence and the predicted amino acid sequence of the
      adenovirus type 7 hexon gene were determined. The hydropathy of the hexon
      proteins from human adenovirus types 2, 3, 4, 5, 7, 12, 16, 40, 41, and 48,
      bovine adenovirus type 3, murine adenovirus type 1, and avian adenovirus types 1
      and 10 was analysed. The presence of purines and pyrimidines in the second
      position of the codons was correlated to hydrophilicity and hydrophobicity,
      respectively. Comparison of the hydrophilicity plots of eight hexons showed seven
      hypervariable regions to be distributed on the surface. A large portion of the
      hypervariable regions manifests hydrophilicity. The strength of the surface
      charge accumulated on the hydrophilic and hydrophobic regions correlated to the
      tissue tropism of the different adenovirus types. Analysis of codon usage for
      adenovirus hexons showed that among synonymous codons those with cytidine in the
      third position were preferably used to a great extent. Analysis of the nucleotide
      and amino acid sequence pair distances and the phylogenetic tree of 14 hexon
      proteins showed members of subgenera B, D and E to be closely related, especially
      Ad4 and Ad16, and subgenus A to be closely related to subgenus F.

PMID- 9267446
TI  - Detection and genetic differentiation of human astroviruses: phylogenetic
      grouping varies by coding region.
AB  - Astroviruses are single-stranded, positive-sense RNA viruses that are associated
      with gastroenteritis in humans and animals. We describe a reverse transcription
      polymerase chain reaction (RT-PCR) assay using primers targeted to a
      nonstructural protein coding region that allowed sensitive detection and genetic
      typing of representative strains of seven astrovirus serotypes. Phylogenetic
      analysis of the nucleotide sequences of PCR products from the reference strains
      and several wild isolates indicated two distinct genogroups of sequences in open
      reading frame 1a (ORF 1a). These genogroups correlated with serotype: genogroup A
      included strains of types 1 to 5, while genogroup B included strains of types 6
      and 7. This phylogenetic arrangement differs from the nearly equidistant
      clustering of serotypes seen when comparing nucleotide sequences from either ORF
      1b or ORF 2. It is possible that recombination was responsible for the observed
      difference in genetic relationships.

PMID- 9267447
TI  - The development of early vs. late onset mucosal disease is a consequence of two
      different pathogenic mechanisms.
AB  - Bovine viral diarrhea (BVD) virus is the causative agent of fatal mucosal disease
      (MD) of cattle. Experimental induction of MD can be achieved by superinfection of
      calves persistently viremic with a noncytopathic (ncp) BVD virus using an
      antigenically similar cytopathic (cp) BVD virus. Here we describe the
      characterisation of BVD viruses isolated from three cases of experimentally
      induced MD. One animal developed clinical symptoms two weeks after superinfection
      (early onset MD), while the onset of disease in the other two cases occurred with
      a delay of months (late onset MD). Antigenic characterisation of the viruses was
      performed using a panel of monoclonal antibodies against the E2 glycoprotein. For
      genetic analysis, RT-PCR was applied to amplify specific insertions and
      duplications in the NS2-3 genomic region of the cp BVD viruses. In addition,
      these amplicons and fragments of the viral E2 genes were sequenced. The results
      showed that in the case of early onset MD the cp BVD virus isolated after begin
      of disease was identical to the one used for superinfection. In contrast, the cp
      BVD viruses isolated from the two animals with late onset MD were obviously the
      result of genetic recombinations between the persistent ncp and the
      superinfecting cp BVD viruses. We conclude that early and late onset MD are the
      consequence of different pathogenic mechanisms.

PMID- 9267448
TI  - Grapevine berry inner necrosis, a new trichovirus: comparative studies with
      several known trichoviruses.
AB  - Biological, morphological and serological properties of grapevine berry inner
      necrosis virus (GINV), the casual virus of grapevine berry inner necrosis disease
      occurring in Japan, were compared with those of several known trichoviruses. Host
      range and particle length of GINV were quite similar to those of apple chlorotic
      leaf spot trichovirus (ACLSV). In ultrathin sections of the infected tissues,
      GINV particles existed in aggregated masses in the cytoplasm of vascular
      parenchyma and mesophyll cells. No virus specific inclusion bodies, such as
      pinwheels, viroplasmas or vesicles were observed. Serological relationships were
      not found between GINV and ACLSV, grapevine virus A or grapevine virus B. The
      cDNAs of the 3'-terminal region of the GINV genome were synthesized from poly
      (A)+RNAs extracted from infected tissues by PCR-selected cDNA subtraction and 3'
      RACE PCR. The sequence of the 3'-terminal 2469 nucleotides contained three open
      reading frames (ORF) encoding a protein with the conserved motifs of RNA
      polymerase (ORF1), a 39 kDa putative movement protein (ORF2) and a 22 kDa protein
      (ORF3). The 22 kDa protein expressed in Escherichia coli reacted with antiserum
      against GINV, indicating that it is the coat protein of GINV. Polymerase and coat
      protein amino acid sequence comparisons and phylogenetic analyses with nine
      species of the genera Trichovirus and Capillovirus indicated that GINV is a new
      trichovirus relatively close to ACLSV.

PMID- 9267449
TI  - A novel synthetic reversible inhibitor of sialidase efficiently blocks secondary
      but not primary influenza virus infection of MDCK cells in culture.
AB  - The sodium salts of 2-difluoromethyl-phenyl-alpha-ketoside of N-acetyl-neuraminic
      acid (compound 1) and of 4-difluoromethyl-2-methoxy-phenyl-alpha-ketoside of N
      acetylneuraminic acid (compound 2) were designed as potential mechanism-based
      inhibitors of sialidase. In vitro both of these compounds competitively inhibited
      the sialidases of Clostridium perfringens and of influenza virus A/HK/1/68.
      Inhibition was irreversible with the sialidase of Clostridium perfringens whereas
      it was reversible with that of A/HK/1/68. Compound 2 did not inhibit the
      hemagglutinin of the virus but exhibited significant anti-influenza activity when
      added to the medium of Madin-Darby canine kidney (MDCK) cells infected by
      influenza virus. In non-infected MDCK cells no inhibition of cellular sialidase
      was observed. Compound 2 did not block primary infection, but inhibited the
      release of progeny virus from infected cells. Even after 8 passages in its
      presence, no resistant strains were detected. Because of its high Ki (8 x 10(-5)
      M) compared to the low Ki (1' x 1(-10) M) of 4 guanidino-Neu 5 Ac 2en and its
      reversible inhibition of viral sialidase, its development as an anti-influenza
      agent is no longer envisaged. Nevertheless, as a mechanism-based irreversible
      inhibitor of the bacterial enzyme, it could at least be useful for investigating
      the intrinsic role of sialidase in infections caused by this strain.

PMID- 9267451
TI  - A worldwide survey of tomato yellow leaf curl viruses.
AB  - The name tomato yellow leaf curl virus (TYLCV) has been given to several whitefly
      transmitted geminiviruses affecting tomato cultures in many tropical and
      subtropical regions. Hybridization tests with two DNA probes derived from a
      cloned isolate of TYLCV from Israel (TYLCV-ISR) were used to assess the
      affinities of viruses in naturally infected tomato plants with yellow leaf curl
      or leaf curl symptoms from 25 countries. Probe A which included most of the
      intergenic region was expected to detect only isolates closely related to TYLCV
      ISR, especially after high stringency washes. In contrast probe B, which included
      the full-length genome, was expected to detect a wide range of whitefly
      transmitted geminiviruses. Tomato samples from six countries in the Middle East,
      from Cuba or the Dominican Republic proved to be closely related to TYLCV-ISR and
      probably were infected by strains of the same virus. Samples from Senegal and
      Cape Verde Islands were also related to the Middle Eastern virus. Samples from
      nine other countries in the western Mediterranean area, Africa, or South-East
      Asia were more distantly related and probably represent one or more additional
      geminivirus species. Samples from five countries in Africa, Central or South
      America gave hybridization signals with the full-length viral genome, only after
      low stringency wash, indicating that these samples were infected by remote
      viruses. These results were supported by DNA and protein sequence comparison,
      which indicate that tomato geminiviruses fall into three main clusters
      representing viruses from 1) the Mediterranean/Middle East/African region, 2)
      India, the Far East and Australia, and 3) the Americans. Within the first
      cluster, two sub-clusters of viruses from the western Mediterranean or from the
      Middle East/Caribbean Islands were distinguished. The incidence of tomato yellow
      leaf curl diseases has increased considerably between 1990 and 1996.

PMID- 9267450
TI  - Taxonomic changes in tailed phages of enterobacteria.
AB  - Out of 136 new phages, 80 (59%) are classified into 23 species according to
      morphology and physicochemical properties. Six new species are described and
      species beta 4, from a previous classification scheme, is renamed T1. The
      morphology of 36 phage species is schematically represented.

PMID- 9267452
TI  - Human cytomegalovirus open reading frame UL11 encodes a highly polymorphic
      protein expressed on the infected cell surface.
AB  - Human cytomegalovirus (HCMV) open reading frame (ORF) UL11 locates within a
      polymorphic region of the viral genome identified previously by a restriction
      fragment-length-polymorphism. We report here that ORF UL11 encodes a polymorphic
      protein expressed on the surface of HCMV-infected cells. First, we determined the
      nucleotide sequence of ORF UL11 from ten strains and compared it among the
      strains. Out of 205 amino acids consisting of the predicted N-terminal region
      beside the putative transmembrane stretch in strain AD169, 88 residues were
      divergent on more than one strain. In contrast, the predicted C-terminal side
      including the putative transmembrane domain was identical at the amino acid
      sequence level. In addition, the number and location of predicted cysteine
      residues were also conserved. Next, we screened a cDNA library from HCMV-infected
      cells and obtained a cDNA clone containing the full-length ORF UL11. Finally, we
      identified the gene product of UL11 on the surface of HCMV-infected cells by FACS
      analysis with polyclonal antibodies generated against a glutathione S
      transferase/UL11 fusion protein. The fusion protein contained a region within the
      N-terminal side next to the predicted transmembrane stretch. These results
      indicate that the N-terminal side of UL11 protein containing variable amino acid
      residues protrudes from the infected cell surface.

PMID- 9267453
TI  - Human T-lymphotropic virus type II infection in Vietnamese thalassemic patients.
AB  - Anti-human T-lymphotropic virus type I/II (HTLV-I/II) antibodies were screened by
      particle agglutination test in a total of 66 patients with thalassemia major who
      received multiple transfusion from paid donors at the Blood Transfusion
      Hematology Center of Ho Chi Minh City in South Vietnam. HTLV-II infection was
      confirmed in 6 patients (9.1%) by Western blot analysis and/or polymerase chain
      reaction. Phylogenetic analysis revealed that long terminal repeat sequences of
      HTLV-II proviruses from 5 thalassemic patients in Vietnam belonged to the same
      phylogenetic subgroup of HTLV-IIb as those from intravenous drug abusers in North
      America and Europe. These data shed light on the route of introducing HTLV-II
      into Vietnam.

PMID- 9267454
TI  - Sequence and phylogenetic analyses of highly virulent infectious bursal disease
      virus.
AB  - The nucleotide sequences of the genome segments A and B encoding the precursor
      polyprotein (NH2-VP2-VP4-VP3-COOH) and VP1 were determined for a highly virulent
      strain of infectious bursal disease virus (IBDV). The precursor polyprotein and
      VP1 coding regions of highly virulent OKYM strain consisted of 3039 nucleotides
      (1012 deduced amino acids) and 2640 nucleotides (879 deduced amino acids),
      respectively. Comparison of the deduced amino acid sequences of the highly
      virulent IBDV (HV-IBDV) with other serotype 1 and 2 sequences revealed 17 amino
      acid residues which were conserved only in the HV-IBDV. Among the 17 unique amino
      acid differences, 8 were in VP1, 4 were in VP2, 3 were in VP3 and 2 were in VP4.
      Although it is impossible to predict the effect of the unique amino acid residues
      without detailed knowledge of the three-dimensional structure and function of the
      proteins, they could affect the virulence of HV-IBDV. Alignment of the nucleic
      acid sequences of precursor polyprotein, VP1, VP2, VP3 and VP4 coding regions
      followed by distance analysis allowed the generation of phylogenetic trees. The
      same tree topology was obtained for the nucleotide sequence of precursor
      polyprotein, VP2, VP3 and VP4. On the other hand, the tree topology of VP1 was
      quite different from that obtained for the nucleotide sequence of precursor
      polyprotein, VP2, VP3 and VP4. These findings indicate that not a genetic
      recombination but a genetic reassortment may play an important role in the
      emergence of HV-IBDV.

PMID- 9267455
TI  - Phylogenetic analysis of feline immunodeficiency virus isolated from cats in
      Taiwan.
AB  - Feline immunodeficiency virus was isolated from four cats in Taiwan. The isolates
      were designated TI-1, TI-2, TI-3 and TI-4. Each was isolated from PBMCs following
      co-cultivation of PBMCs with a feline T-lymphoblastoid cell line (MYA-1 cells).
      However, the Taiwanese isolates did not grow in a feline kidney cell line (CRFK
      cells). The nucleotide sequences of the V3-V5 region of the envelope gene of the
      Taiwanese isolates were determined and compared with those of previously
      described isolates. Phylogenetic analysis of this region indicates that Taiwanese
      isolates belong to subtype C.

PMID- 9267456
TI  - Human calicivirus genogroup II capsid sequence diversity revealed by analyses of
      the prototype Snow Mountain agent.
AB  - The Snow Mountain agent (SMA) is the prototype genogroup II and serotype 3 human
      calicivirus responsible for epidemic outbreaks of acute gastroenteritis. We have
      cloned the region of the SMA genome that encodes the single capsid protein. The
      predicted amino acid sequence of the capsid protein is distinct from other
      calicivirus strains that have been termed SMA-like based on sequence similarity
      between the RNA polymerase regions and IEM reactivity. In a previous report, a
      high sequence similarity in a small region of the RNA polymerase between SMA and
      another strain, OTH-25, suggested that the capsid proteins of OTH-25 and SMA
      would be very similar. In this report, we show that the capsid proteins of OTH-25
      and SMA are more distinct than was predicted by similarity in the RNA polymerase.
      In addition, phylogenetic analysis of a region of the RNA polymerase and of the N
      terminal conserved domain of the capsid protein of 12 human caliciviruses
      resulted in trees with different topologies, suggesting that recombination has
      occurred within this group of viruses. Molecular characterization of the
      prototype calicivirus strains is important in determining the relationships
      between capsid similarity at the amino acid level, genetic grouping by sequence
      comparison, and antigenic reactivity.

PMID- 9267457
TI  - Genetic variation in the VP7 gene of human rotavirus serotype 3 (G3 type)
      isolated in China and Japan.
AB  - Sequence analysis of the VP7 gene was performed on twenty-one human isolates of
      serotype 3 related-rotavirus in China and Japan. The five Chinese isolates were
      found to be not similar to the 16 Japanese isolates and to SA11 (simian
      rotavirus). The Chinese isolates, especially CHW2 and CH-32, were different from
      the major serotype 3 human isolates. AU-1 and 02/92 which previously showed a
      wider spacing between RNA segments 10 and 11 by RNA polyacrylamide gel
      electrophoretic analysis, were more closely related to each other and could be
      differentiated from the other Chinese and Japanese isolates. For these reasons,
      serotype 3 viruses were considered to be intraserotypically more heterologous
      than serotype 1, 2 and 4 viruses.

PMID- 9267458
TI  - Neutralization of rotavirus and recognition of immunologically important epitopes
      on VP4 and VP7 by human IgA.
AB  - Rotavirus is an important cause of gastroenteritis in young children. Locally
      produced antibodies in the intestinal mucosa are proposed to play an important
      role in the defence against rotavirus infection, but it is not established
      whether IgA alone can neutralize rotavirus, nor if IgA antibodies recognize
      epitopes involved in protective immunity. To evaluate whether human IgA plays a
      role in virus neutralization, serum IgA was purified from nineteen rotavirus
      seropositive individuals and examined for its neutralizing capacity by a
      peroxidase focus reduction test. In all nineteen sera IgA neutralizing antibodies
      against serotype 3 (rhesus rotavirus) were demonstrated. Purified IgA was further
      investigated and shown not only to neutralize rotavirus in solution but also to
      neutralize rotavirus already pre-bound to epithelial cells (MA-104). IgA epitope
      blocking assays with monoclonal antibodies directed against heterotypic epitopes
      on VP4 and VP7, revealed that IgA antibodies from 4/16 sera recognized epitopes
      on VP4, while 5/16 sera recognized a VP7 epitope. When whole sera were
      investigated for comparison 7 and 9/16 sera recognized epitopes on VP4 and VP7
      respectively.

PMID- 9267459
TI  - Detection and characterization of a distinct type of beet necrotic yellow vein
      virus RNA 5 in a sugarbeet growing area in Europe.
AB  - A fifth beet necrotic yellow vein virus (BNYVV) RNA species has been detected in
      Europe in sugarbeet infected with P-type BNYVV. Very little sequence variation
      was found between two European sources of this RNA 5*, but considerable
      differences were detected between these two European sources on the one hand and
      the four Japanese sources recently analysed by Kiguchi et al. on the other. The
      BNYVV RNA 5-encoded 26 K proteins share a stretch of six amino acids (FRGPGN)
      with the BNYVV RNA 3-encoded 25 K protein which may be of interest in view of the
      reported interactions between the two RNAs in pathogenicity.

PMID- 9267460
TI  - Guidelines to the demarcation of virus species.

PMID- 9267462
TI  - Successful bone marrow transplantation in sensitized aplastic anemia patients
      using total lymphoid irradiation for conditioning: long-term follow-up.
AB  - Between June 1986 and November 1994, 22 previously transfused patients with
      severe aplastic anemia (SAA) were treated with high-dose cyclophosphamide (CY)
      (50 mg/kg over 4 consecutive days) and 7 Gy total lymphoid irradiation (TLI) in
      two fractions before allogeneic bone marrow transplantation (BMT) from HLA
      identical sibling. Graft-versus-host-disease (GVHD) prophylaxis included the
      combination of methotrexate and cyclosporine A in all cases. Actuarial survival
      at 5 years is 73 +/- 9 per cent for the entire group and 86 +/- 13 per cent for
      the seven patients < or = 18 years. The incidence of graft failure was 0 per
      cent, and of acute GVHD and chronic GVHD was 31.5 per cent and 24 per cent
      respectively. Prolonged interval from diagnosis to BMT adversely influenced
      survival (P = 0.03). No hypothyroidism or secondary malignancies have been
      documented in this series. Our findings indicate that survival with CY-TLI is
      comparable to that obtained using preparative regimens without radiation. The
      changing role of radiotherapy in pretransplant immunosuppression for SAA is
      discussed.

PMID- 9267461
TI  - High incidence of secondary myelodysplastic syndromes following PROMACE-MOPP and
      involved field radiotherapy for localized gastric non-Hodgkin's lymphomas.
AB  - The incidence of secondary myelodysplastic syndromes (MDS) are rarely reported in
      an homogeneous patient population treated for non-Hodgkin's lymphoma (NHL). Less
      than 10 per cent of secondary MDS are usually observed in patients treated for
      Hodgkin's disease and NHL. Data on the incidence of secondary MDS induced by
      modern chemotherapeutic regimens is needed. Between January 1985 and January
      1989, 20 patients with localized gastric non-Hodgkin's lymphomas (stage I to IIE)
      were prospectively treated at the Institut Gustave-Roussy with PROMACE-MOPP multi
      agent chemotherapy and involved-field irradiation. The mean age was 54 years
      (range 23 to 69 years). Seven patients died while on therapy or relapsed 2 to 28
      months after therapy. Thirteen patients were followed up for at least 5 years.
      Three of the 13 long-term survivors (23 per cent) developed a myelodysplastic
      syndrome (MDS) 48, 62 and 72 months after the end of therapy. Cytogenetic
      analysis was performed in two cases and showed-7 and 18q- in one case,
      t(9;21)(q13;q22), 21q+, i17q in the other case. PROMACE-MOPP plus radiotherapy
      should not be recommended in patients with localized gastric non-Hodgkin's
      lymphoma due to the high risk of developing secondary myelodysplastic syndromes.

PMID- 9267463
TI  - Primary B cell lymphoma of the mediastinum.
AB  - Primary B cell mediastinal lymphoma has been recognized as a distinct entity
      recently. This is a retrospective study to define the clinical features and
      treatment outcome over a 10-year period. Twenty-four consecutive patients
      (male/female: 11/13) with B cell lymphoma primarily involving the mediastinum
      were studied. The median age was 34 years. Symptoms were mainly referrable to the
      chest, with superior vena cava syndrome (SVCO) present in one-third of the
      patients. Bulky disease was present in over half (58 per cent) and B symptoms
      were present in 38 per cent of patients. The overall CR rate was 70 per cent and
      the 5-year OS rates were 56 per cent and 72 per cent for all and CR patients
      respectively. Five (71 per cent) primary refractory patients and four (66 per
      cent) relapsed patients died despite salvage therapy. Six relapses occurred at a
      median of 6 months from treatment. This study showed that primary large B cell
      lymphoma of the mediastinum is a clinically distinct entity affecting young
      patients. A significant proportion attained CR and overall, more than half
      achieved prolonged remission, and most of the relapses occurred early. However,
      those who failed to attain CR or relapsed still had a poor outcome. An intensive
      therapy such as autologous bone marrow transplant has to be considered in this
      subgroup of patients.

PMID- 9267464
TI  - Different effects of cyclic AMP and butyrate on eosinophilic differentiation,
      apoptosis and bcl-2 expression of a human eosinophilic leukemia cell line, EoL-1.
AB  - A human eosinophilic leukemia cell line, EoL-1, stopped proliferating at the G1
      phase, differentiated into eosinophilic granule-containing cells, and died by
      apoptosis when stimulated with dibutyryl cyclic AMP (dbcAMP). To clarify the
      effects of dbcAMP, the effects of butyrate and cAMP-increasing reagents,
      prostaglandin E2 (PGE2) and forskolin, on EoL-1 cellular differentiation and
      apoptosis were examined and compared. PGE2 and forskolin but not butyrate induced
      differentiation to eosinophilic granule-containing cells, suggesting that cAMP
      played a primary role in eosinophilic differentiation of EoL-1 cells. PGE2,
      forskolin and butyrate, when used alone, did not induce apoptosis of EoL-1 cells
      significantly at the concentrations used, but sequential stimulation of EoL-1
      cells with the cAMP-increasing reagents and butyrate showed that butyrate induced
      further maturation and apoptosis of cAMP-induced eosinophilic granule-containing
      cells. These results showed that cAMP and butyrate have different effects on
      eosinophilic differentiation and apoptosis of EoL-1 cells. The cAMP-increasing
      reagents and butyrate also showed different effects on expression of members of
      the bcl-2 family; PGE2 decreased bcl-2 and bax levels, whereas butyrate increased
      the bcl-2 level. PGE2 or PGE2+butyrate, but not butyrate alone, induced bcl-XS
      expression. EoL-1 cells constitutively expressed Fas and anti-Fas antibody
      induced EoL-1 cell death, but the Fas/Fas ligand system was not involved in
      dbcAMP-induced EoL-1 cell apoptosis. The EoL-1 cell line is thus a useful model
      in which to examine differentiation and apoptosis of eosinophilic leukemia cells.

PMID- 9267466
TI  - Anti-biotin antibodies offer superior organelle-specific labeling of mitochondria
      over avidin or streptavidin.
AB  - The mitochondrial matrix contains endogenously biotinylated proteins. These
      proteins can cause unexpected background signal when biotin-avidin- or biotin
      streptavidin-based detection systems are used in immunocytochemistry. Here we
      show that this reactivity can be deliberately exploited, using a simple anti
      biotin reagent, to obtain strong and highly specific labeling of mitochondria by
      both light and electron microscopy. The signal is substantially stronger than
      when either avidin or streptavidin is used to detect the endogenous biotin. These
      results confirm the accessibility of protein-bound endogenous biotin to exogenous
      probes, and localize the biotinylated enzymes to the mitochondrial matrix.

PMID- 9267465
TI  - A phase I trial to assess the value of recombinant human granulocyte colony
      stimulating factor (R-MeTHuG-CSF, filgrastim) in accelerating the dose rate of
      chemotherapy for intermediate and high-grade non-Hodgkin's lymphoma (NHL). The
      Central Lymphoma Group.
AB  - In a multi-centre phase I study we investigated the possibility of reducing the
      interval between courses of standard CHOP (cyclophosphamide 750 mg/m2,
      doxorubicin 50 mg/m2, vincristine 2 mgs day 1, and prednisolone 40 mg/m2 days 1
      8) from 21 days to 15 days and then 10 days using granulocyte colony stimulating
      factor (r-MetHuG-CSF (Amgen)-filgrastim) to accelerate neutrophil recovery.
      Patients received CHOP followed by G-CSF 5 micrograms/kg s.c. from day 2 to the
      day before the next course (e.g. days 2-14 for the 15-day interval). A total of
      28 patients with newly diagnosed intermediate grade or high grade NHL were
      studied. Four patients were studied at a 21-day interval, six patients were
      treated at a 15-day interval and subsequently six patients at a 10-day interval.
      Following analysis of this initial cohort, a further 12 patients were evaluated;
      four at the 15-day interval, and eight at the 10-day interval. No dose-limiting
      toxicity was seen in the four patients receiving 21-day CHOP. Dose-limiting
      toxicity was seen in 4/10 patients treated at the 15-day interval (M:F 7:3,
      median age 55.5, range 39-67 years). This consisted of infection in two patients,
      recurrent infection and debility in a third, and mucositis in a fourth. Seven
      patients experienced one or more infectious episodes requiring antibiotics
      (median number of episodes: 2, range 1-4). Fourteen patients (M:F 4:3, median age
      47.5, range 25-63 years) were treated at the 10-day interval. Dose-limiting
      toxicity was seen in six patients. This consisted of severe mucositis in three
      patients, neutropenia and thrombocytopenia on two separate occasions in one
      patient, and steroid-induced gastritis in two patients. Nine patients had one or
      more documented infections (median: 2, range 1-3) requiring antibiotics, of which
      six were severe (WHO grade 3 or 4). One patient died of Pneumocystis carinii
      (PCP) pneumonia. In summary, G-CSF (filgrastim) will facilitate the shortening of
      the dosage interval between cycles of CHOP chemotherapy due to accelerated
      hematological recovery. However, non-hematological toxicity due to the shorter
      dosage interval is increased and infective episodes are frequent.

PMID- 9267467
TI  - Accumulation of advanced glycation endproducts in the rat nephron: link with
      circulating AGEs during aging.
AB  - The accumulation of advanced glycosylation end products (AGEs) is believed to be
      a factor in the development of aging nephropathy. We have attempted to establish
      a link between the formation of AGEs and the onset of renal impairment with
      aging, indicated by albuminuria, using a fluorescence assay and
      immunohistochemical detection of AGEs in the renal extracellular matrix in rats.
      The fluorescence of collagenase-digested Type IV collagen from GBM increased with
      age, from 1.65 +/- 0.05 AU/mM OHPro (3 months) and 1.58 +/- 0.04 (10 months) to
      2.16 +/- 0.06 (26 months) (p < 0.001) and 2.53 +/- 0.18 (30 months) (p < 0.001).
      In contrast, the extent of early glycation products significantly decreased from
      5.35 +/- 0.25 nmol HCHO/nmol OHPro at 3 months to 3.14 +/- 0.19 at 10 months (p <
      0.001), 3.42 +/- 0.38 at 26 months, and 0.74 +/- 0.08 at 30 months (p < 0.001).
      The urinary fluorescence of circulating AGE rose from 2.42 +/- 0.15 AU/mg protein
      (3 months), 1.69 +/- 0.07 (10 months), to 4.63 +/- 0.35 (26 months) (p < 0.01)
      and 4.73 +/- 0.72 (30 months), while the serum fluorescence increased from 0.39
      +/- 0.02 AU/mg protein at 3 months and 0.43 +/- 0.02 at 10 months to 0.59 +/-
      0.04 at 26 months (p < 0.001) and 0.54 +/- 0.03 at 30 months (p < 0.04).
      Polyclonal antibodies raised against AGE RNase showed faint areas of AGE
      immunoreactivity in mesangial areas in the nephrons of young rats. The
      immunolabeling of Bowman's capsule, the mesangial matrices, and the peripheral
      loops of glomerular and tubule basement membranes increased with rat age. The
      increase in circulating AGE peptides parallels the accumulation of AGEs in the
      nephron, and this parallels the pattern of extracellular matrix deposition,
      suggesting a close link between AGE accumulation and renal impairment in aging
      rats.

PMID- 9267468
TI  - Fibrillin-1 in human cartilage: developmental expression and formation of special
      banded fibers.
AB  - The molecular basis for Marfan's syndrome (MS), a heritable disorder of
      connective tissue, is now known to reside in mutations in FBN1, the gene for
      fibrillin-1. Classic phenotypic manifestations of MS include several skeletal
      abnormalities associated primarily with overgrowth of long bones. As a first step
      towards understanding how mutations in FBN1 result in skeletal abnormalities, the
      developmental expression of fibrillin-1 (Fib-1) in human skeletal tissues is
      documented using immunohistochemistry and monoclonal antibodies demonstrated here
      to be specific for Fib-1. At around 10-11 weeks of fetal gestation, Fib-1 is
      limited in tissue distribution to the loose connective tissue surrounding
      skeletal muscle and tendon in developing limbs. By 16 weeks, Fib-1 is widely
      expressed in developing limbs and digits, especially in the perichondrium, but it
      is apparently absent within cartilage matrix. Fib-1 appears as a loose meshwork
      of fibers within cartilage matrix by 20 weeks of fetal gestation. Until early
      adolescence, Fib-1 forms loose bundles of microfibrils within cartilage. However,
      by late adolescence, broad banded fibers composed of Fib-1 are found accumulated
      pericellularly within cartilage. Because these fibers can be extracted from
      cartilage using dissociative conditions, we postulate that they are laterally
      packed and crosslinked microfibrils. On the basis of these findings, we suggest
      that the growth-regulating function of Fib-1 may reside persistently within the
      perichondrium. In addition, the accumulation of special laterally crosslinked Fib
      1 microfibrils around chondrocytes during late adolescence suggests that growth
      regulating activities may also be performed by Fib-1 at these sites.

PMID- 9267469
TI  - Immunocytochemical evidence that GLUT4 resides in a specialized translocation
      post-endosomal VAMP2-positive compartment in rat adipose cells in the absence of
      insulin.
AB  - Insulin stimulates glucose transport in rat adipose cells through the
      translocation of GLUT4 from a poorly defined intracellular compartment to the
      cell surface. We employed confocal microscopy to determine the in situ
      localization of GLUT4 relative to vesicle, Golgi, and endosomal proteins in these
      physiological insulin target cells. Three-dimensional analyses of GLUT4
      immunostaining in basal cells revealed an intracellular punctate, patchy
      distribution both in the perinuclear region and scattered throughout the
      cytoplasm. VAMP2 closely associates with GLUT4 in many punctate vesicle-like
      structures. A small fraction of GLUT4 overlaps with TGN38-mannosidase II, gamma
      adaptin, and mannose-6-phosphate receptors in the perinuclear region, presumably
      corresponding to late endosome and trans-Golgi network structures. GLUT4 does not
      co-localize with transferrin receptors, clathrin, and Igp-120. After insulin
      treatment, GLUT4 partially redistributes to the cell surface and decreases in the
      perinuclear area. However, GLUT4 remains co-localized with TGN38-mannosidase II
      and gamma-adaptin. Therefore, the basal compartment from which GLUT4 is
      translocated in response to insulin comprises specialized post-endosomal VAMP2
      positive vesicles, distinct from the constitutively recycling endosomes. These
      results are consistent with a kinetic model in which GLUT4 is sequestered through
      two or more intracellular pools in series.

PMID- 9267470
TI  - Chromatin condensation in erythropoiesis resolved by multipixel spectral imaging:
      differentiation versus apoptosis.
AB  - Chromatin condensation and nuclear organization of May-Grunwald-Giemsa (MGG)
      stained normal erythropoietic bone marrow cells and apoptotic red cell precursors
      were resolved by spectral bio-imaging. Multipixel spectra were obtained from
      single cells displaying a range of wavelengths of both transmitted and absorbed
      light. Two groups of spectra, of low- and high-intensity transmitted light, were
      revealed in the nuclei of each cell. The absorbance spectra served for the
      reconstruction of "absorbance images" depicting the affinity of MGG stain for the
      chromatin of proerythroblasts and of basophilic, polychromatic, and
      orthochromatic normoblasts. The localization of different spectral components in
      the nuclei was resolved employing two mathematical methods, spectral similarity
      mapping and principal component analysis. Novel structures of high symmetry
      revealing windmill-like organization were detected in basophilic, polychromatic,
      and orthochromatic normoblast cells. Matching structures were detected in
      apoptotic normoblasts obtained from an agnogenic myeloid metaplasia patient.
      Apoptosis was associated with a gradual breakdown of the ordered arrays in the
      nucleus. We propose that DNA cleavage may lead to fragmentation of the
      symmetrical windmill-like superstructure of the basic nuclear domains.

PMID- 9267471
TI  - Expression of human group II phospholipase A2 in transgenic mice.
AB  - Group II phospholipase A2 (PLA2) has been proposed to play an important role in
      inflammation and defense against bacterial infection. We investigated tissues of
      transgenic mice expressing the human group II PLA2 gene by immunohistochemistry
      using rabbit anti-human group II PLA2 antibodies, and by in situ hybridization by
      probing with human group II PLA2 mRNA anti-sense (test) and sense (control)
      riboprobes. By immunohistochemistry, human group II PLA2 was found in various
      mouse tissues and cell types including hepatocytes, proximal tubule cells of the
      kidney, epithelial cells of the renal pelvis, urinary bladder and ureter,
      granulosa cells of Graafian follicles, aortic intima and media, cartilage,
      epiphyseal bone, bronchial epithelial cells, and connective tissue cells in the
      dermis. By in situ hybridization, group II PLA2 mRNA was localized in
      hepatocytes, epidermal cells, dermal cells, connective tissue fibroblasts,
      epithelial and smooth muscle cells of the urinary bladder, and cells of Bowman's
      capsule. These results show that human group II PLA2 is expressed in large
      amounts in hepatocytes and many extrahepatic tissues of the transgenic mice.
      These animals provide a useful new tool for studies on the metabolism, in vivo
      effects, and physiological and pathological roles of phospholipase A2.

PMID- 9267472
TI  - Innervation of the sheep pineal gland by nonsympathetic nerve fibers containing
      NADPH-diaphorase activity.
AB  - We used the NADPH-diaphorase histochemical method as a potential marker for
      nitric oxide synthase (NOS)-containing nerve fibers innervating the pineal gland
      of the sheep. Nerve fibers containing NADPH-diaphorase activity provide dense
      innervation of the sheep pineal gland. The nerve fibers were located in the
      pineal capsule, in the connective tissue septae separating the lobull of the
      gland, and penetrating between the pinealocytes. The nerve fibers were either
      smooth or endowed with boutons en passant. After bilateral removal of the
      superior cervical ganglion, the dense network of NADPH-diaphorase-positive fibers
      was still present in the gland. Ganglionectomy affected neither the distribution
      nor the appearance of the NADPH-diaphorase-positive fibers. Most of the NADPH
      diaphorase-positive fibers also contained peptide histidine isoleucine and
      vasoactive intestinal polypeptide, and a comparatively smaller fraction contained
      neuropeptide Y. Pinealocytes never exhibited NADPH-diaphorase activity. These
      results demonstrate a major neural input to the sheep pineal gland with NADPH
      diaphorase-positive nerve fibers of nonsympathetic origin.

PMID- 9267473
TI  - Cytochemical localization of ouabain-sensitive, K(+)-dependent p
      nitrophenylphosphatase activity in the facial nerve of reserpinized guinea pigs.
AB  - Ion-transporting Na,K-ATPase plays an essential role in nerve conduction. To
      clarify the cytochemical effects of reserpine on transport Na,K-ATPase activity,
      the localization of ouabain-sensitive, K(+)-dependent p-nitrophenylphosphatase (K
      NPPase) activity was investigated in the facial nerves of normal and reserpinized
      guinea pigs using a cerium-based method. In the normal facial nerve, the reaction
      product of K-NPPase activity was observed on the internodal axolemma and Schmidt
      Lanterman incisures. In the Ranvier nodes, enzyme activity was localized to the
      paranodal and nodal axolemma. In the reserpinized nerves, reaction product was
      detectable on the nodal axolemma but was undetectable on the other parts of the
      axolemma. Nodal K-NPPase was not affected by reserpine treatment. Therefore, the
      transport Na,K-ATPase on the nodal axolemma might differ from that on the other
      parts of the axolemma. Allowing reserpinized animals to survive. Two different
      ouabain-sensitive K-NPPase reactivities, "reserpine-sensitive" and "reserpine
      resistant," might be present in the facial nerve of guinea pigs.

PMID- 9267474
TI  - Immunohistochemical analysis of DNA synthesis during chronic stimulation with
      isoproterenol in mouse submandibular gland.
AB  - We investigated the numbers of DNA-synthesizing cells in mouse submandibular
      glands (SMGs) during chronic isoproterenol (IPR) administration, using an
      immunohistochemical method with anti-bromodeoxyuridine (BrdU) antibodies. Adult
      and immature female mice were injected with IPR daily or every other day up to a
      total of seven injections. Whereas hypertrophic enlargement of acinar cells
      continued with repeated IPR injections, induction of DNA synthesis was transient.
      With one IPR injection, more than 50% of the acinar cells were induced to
      synthesize DNA, but after five daily injections the numbers of cells in the DNA
      synthetic phase decreased and returned to control values. This pattern was
      basically the same for immature mice and for adult mice stimulated by IPR every
      other day. The responsiveness of the SMGs of immature mice to IPR was somewhat
      lower than that of adults. Prolongation of the interval between injections of
      IPR, compared to daily injections, did not cause sustained induction of DNA
      synthesis. These data suggest that the hypertrophic enlargement and the induction
      of DNA synthesis by IPR are mediated through different intracellular pathways
      after the stimulation of beta-adrenergic receptors, and that the regulatory
      mechanism for the induction of DNA synthesis is complex.

PMID- 9267475
TI  - Visualization of beta-galactosidase by enzyme and immunohistochemistry in the
      olfactory bulb of transgenic mice carrying the LacZ transgene.
AB  - In the olfactory bulb (OB) of a transgenic mouse line that carries the bacterial
      LacZ gene under the control of the 5'-regulatory region of the GAD67 gene,
      expression of the beta-galactosidase was confined almost exclusively to the non
      GABAergic mitral and tufted cells. By light microscopy, enzyme histochemistry
      showed strong staining in the cell bodies and faint diffuse staining in the axons
      and dendrites. With immunohistochemistry for beta-galactosidase the entire
      cytoplasm, including the axons and dendrites, was strongly stained. By electron
      microscopy, beta-galactosidase enzyme histochemistry resulted in a submicroscopic
      reaction product that was diffusely distributed in the cytoplasm of neurons. In
      addition, large deposits of the reaction product were also seen attached to the
      cytoplasmic side of the membranes. In contrast, when the intracellular
      localization of beta-galactosidase was determined by immunohistochemistry,
      homogeneous cytoplasmic staining was obtained that filled the entire cytoplasm
      including the terminal dendrites and fine axons. Therefore, synaptic contacts of
      the beta-galactosidase-positive output neurons with other beta-galactosidase
      negative neuronal cells were readily recognized in the OB. As we demonstrated,
      transgenic mouse lines expressing the LacZ reporter gene in a well-defined
      neuronal subpopulation can be used to follow beta-galactosidase-positive neurons
      and to directly identify their synaptic connections.

PMID- 9267476
TI  - Patterns of hyaluronan staining are modified by fixation techniques.
AB  - The apparent intensity of hyaluronan (HA) staining in tissue sections can vary as
      a function of fixation techniques. We examined the histochemical distribution of
      HA in normal human skin using an HA-specific binding peptide derived from bovine
      nasal cartilage. The HA, particularly in the dermis, was best preserved in
      sections fixed in 10% acid-formalin with 70% ethanol. In contrast, sections fixed
      in the routine 10% neutral-buffered formalin had a much weaker intensity of HA
      staining. Furthermore, acid-formalin/ethanol-fixed sections retained much of
      their apparent HA after incubation with saline, in contrast to the neutral
      formalin-fixed sections, in which most of the stainable HA was lost. Such marked
      differences in staining intensity were not observed in slides stained with Alcian
      blue, a procedure presumed to stain HA as well as other glycosaminoglycans.
      Staining using the HA binding peptide was entirely absent when sections were
      first preincubated in hyaluronidase, whereas similar Alcian blue-stained sections
      retained most of their staining intensity. Caution should be exercised in
      evaluating the distribution of HA in tissues using the HA binding peptide,
      particularly when different fixation techniques among several laboratories are
      being compared. In addition, the ability to evaluate the HA content of tissues
      using Alcian blue staining should be reconsidered. The sulfated
      glycosaminolglycans of the "ground substance" appear to be the predominant
      substrates for Alcian blue.

PMID- 9267477
TI  - Protease antigen recovery decreases the specificity of bromodeoxyuridine
      detection in formalin-fixed tissue.
AB  - Incorporation of halogenated nucleotide analogues is often used to assess DNA
      synthesis and to quantitate cellular proliferation. Multiple antibodies have been
      developed to bromodeoxyuridine (BrdUrd) and it is the most frequently utilized
      substrate. Because the immunodetection of incorporated BrdUrd requires DNA
      denaturation or nuclease digestion, most of these antibodies are not reactive in
      tissues or cells fixed with crosslinking agents. Antigen retrieval techniques
      utilizing protease digestion restore BrdUrd antigenicity and permit the detection
      of BrdUrd in formalin-fixed tissue. However, during the development of a double
      label immunohistochemical protocol to quantitate proliferating alveolar Type II
      cells, we noted nucleus-specific staining in lung sections from animals that had
      not received BrdUrd. Therefore, we systematically analyzed the specificity of the
      immunohistochemical detection of incorporated BrdUrd in formalin-fixed tissue
      after protease digestion. Enzymatic antigen recovery diminished the specificity
      of the BrdUrd reaction product and caused false-positive staining with the BU-1,
      B44, and BR3 monoclonal antibodies. Staining was less prominent with Bu20a but
      was more specific. Protease antigen recovery may decrease the specificity of
      BrdUrd immunodetection. Appropriate controls are required when enzymatic
      digestion is used to detect incorporated BrdUrd in formalin-fixed tissue. The
      type and duration of fixation, antibody to BrdUrd, protease, and tissue may
      affect the specificity of the staining pattern.

PMID- 9267478
TI  - Structure, function and gene expression of epithelial mucins.
AB  - In this review the main characteristics, i.e., structure, function and gene
      expression, of the different mucins are discussed. Mucin-type molecules consist
      of a core protein moiety (apomucin) where a number of carbohydrate chains are
      attached to serines and threonines by glycosidic bonds. O-linked carbohydrates
      form up to 80% of the molecule and the length of the glucidic side chains varies
      from one to more than 20 residues. At least eight mucin-like genes have been
      isolated so far, and the main characteristic is the presence of a central domain
      composed of a variable number of "tandem repeats". The sequence homology of the
      central domain among the different members of the mucin-type family is limited,
      indicating that this internal domain is unique for each mucin. Thanks to the
      integrated results of genetic, immunological and biochemical studies, it is now
      possible to identify eight apomucin genes, namely MUC1, MUC2, MUC3, MUC4, MUC5AC,
      MUC5B, MUC6 and MUC7. MUC1 is the best characterized mucin and it is expressed on
      the apical surface of most polarized epithelial cells. The MUC1 gene has been
      cloned and sequenced. The MUC2 gene encodes a typical secretory gel-forming mucin
      which represents the predominant form in human intestinal and colon tissues.
      Another intestinal mucin is MUC3. The MUC4, MUC5AC and MUC5B genes have been
      isolated from a bronchial tissue cDNA library. The MUC4 and MUC5AC genes are
      mainly expressed in the respiratory tract, in gastric and reproductive mucosa,
      while MUC5B is highly detectable only in the bronchial glands. The MUC6 gene is
      expressed by gastric tissue and, recently, MUC7 has been cloned and sequenced
      using a salivary cDNA library.

PMID- 9267479
TI  - Nonstandard fractionation schedules in radiation therapy of head and neck cancer:
      a review.
AB  - The authors present an updated review of the clinical trials on hyperfractionated
      and accelerated fractionation schedules in radiotherapy of head and neck cancer.
      The available results in terms of survival and local control, and acute and late
      toxicity data are summarized in order to show the current status of this research
      field. The new breed of fractionation schedules that are on study, designed on
      the ground of new rationales, are presented as well. Finally, an introductory
      overview of combination therapy including non standard fractionation radiotherapy
      associated with chemotherapy is reported.

PMID- 9267480
TI  - Cancer mortality in Italy, 1993.
AB  - BACKGROUND: Data and statistics are presented on cancer death certification for
      1993 in Italy, updating previous publications covering the period 1955-1992.
      METHODS: Data for 1993 subdivided into 30 cancer sites are presented in 8 tables,
      including age- and sex-specific absolute and percentage frequencies of cancer
      deaths, and crude, age-specific and age-standardized rates, at all ages and
      truncated for the 35-64 year age group. RESULTS: Age-adjusted death certification
      rates (on the world standard population) for all neoplasms declined from 189.8 in
      1992 (and a peak of 199.2 in 1986) to 187.8/100,000 males in 1993, and remained
      stable around 100,000 females. The favorable trends were even larger in middle
      and younger age males, but not in children below age 15, whose overall age
      standardized cancer mortality rates increased for the fourth subsequent year.
      Lung cancer was the leading site of cancer mortality, with over 30,900 deaths.
      For the fifth subsequent year, its rates in males declined, to reach
      56.0/100,000. The decline in lung cancer rates is now established in Italian
      males and is substantial in middle age, whereas the rise in female lung cancer
      rates seems to have leveled off over the last few years. Rates for other major
      cancer sites (intestines, stomach, female breast, prostate, pancreas, leukemias
      and lymphomas) were stable, but some decrease was apparent also in 1993 for
      Hodgkin's disease. CONCLUSIONS: Italian cancer mortality rates in 1993 were
      moderately favorable in males, due to the leveling of the tobacco-related
      epidemic, whereas no appreciable change was registered in females. The persisting
      unfavorable trends in childhood cancer mortality should be investigated.

PMID- 9267481
TI  - Training in colposcopy: experience with a videocolposcopy test.
AB  - The authors evaluate the results of a videocolposcopy test (330 total cases, 12
      cases of histologically confirmed CIN2 or more severe lesions) taken by 9
      accredited and 17 unaccredited colposcopists during 1995. Seven of 9 accredited
      and 4 of 13 unaccredited colposcopists reached the requested standard
      (sensitivity > 90%, biopsy rate < 60%). Performance was definitely better when
      the test was not blind to the cytologic report (4 of 13 reached the requested
      standard) with respect to blind reading (none of 17). The study confirmed that
      colposcopy at unaccredited practices is poorly accurate. Colposcopic assessment
      of patients with abnormal smears should be centralized in accredited practices,
      which should undergo periodic quality control to guarantee screening efficacy.
      Tape-recorded videocolposcopy tests are a good, simple, practical and inexpensive
      method for interobserver quality control of colposcopic performance.

PMID- 9267482
TI  - Frequency of thyroid carcinoma in a recent series of 539 consecutive
      thyroidectomies for multinodular goiter.
AB  - AIMS AND BACKGROUND: The aim of the study was to analyze the frequency of thyroid
      carcinoma in a consecutive series of 539 thyroidectomies for multinodular goiter
      (MNG) and to assess the influence of sex and age as cancer risk factors. METHODS:
      In a 2-year period, 539 patients underwent subtotal or total thyroidectomy for
      MNG at the institute of General Surgery, University of Padova, Padova, Italy: 455
      were females and 84 males (F/M = 5.5/1); mean age was 46 years (min. 17, max 78).
      Only 17 patients (3.1%) (16 females and 1 male) were aged 21 years or less.
      RESULTS: A malignancy was found in 41 patients: 38 females and 3 males; 39 older
      and 2 younger than 21 years. The frequency of cancer in MNG was 7.6%: 8.3% in
      females and 3.6% in males; 7.5% in patients older than 21 and 11.7% under 21
      years. CONCLUSIONS: The combination of MNG and carcinoma should always be
      carefully considered but not overemphasized, and the policy of surgically
      treating all patients with MNG is not justified. Sex and age cannot be considered
      as factors of a higher risk of cancer.

PMID- 9267483
TI  - High-dose epirubicin in locally advanced operable noninflammatory breast cancer:
      a feasibility trial.
AB  - AIMS AND BACKGROUND: Anthracyclines are among the most active agents for the
      treatment of patients with locally advanced breast cancer. The aim of our study
      was to evaluate the feasibility and activity of a relatively high-dose regimen
      with 4-epirubicin plus normal doses of cyclophosphamide over a short period of
      time without the use of hematologic growth factors as adjuvant in resected
      locally advanced breast cancer. METHODS: Between January 1990 and June 1992, 43
      consecutive patients, premenopausal or postmenopausal < 60 yrs, were surgically
      resected and then treated with epirubicin plus cyclophosphamide for at least 4
      cycles (maximum 6). Electron beam (6-10 MeV energy) radiotherapy was delivered on
      the chest wall in patients with pathological skin infiltration (pT4b). RESULTS:
      Median age was 46 years (range, 27-59); 37 were premenopausal and 6
      postmenopausal. The total number of administered cycles was 202 (6 in 15 patients
      and 4 in 28 patients); 195/202 (96.5%) were administered at full dose, and 7
      (3.5%) were reduced to 75% of the planned dosage. The three-year disease-free
      survival was 67% for stage IIIa and 61% for stage IIIb patients. The three-year
      overall survival was 88% and 79%, respectively. Local relapse only was reported
      in one patient (2%), distant relapse in 11 patients (25%), and local and distant
      relapse in four patients (9%). Toxicity was acceptable and mainly hematologic.
      CONCLUSIONS: Our trial showed that the regimen is feasible without the use of
      hematologic growth factors. In this era of cost containment, the use of this
      short-term, high-dose induction course instead of repetitive courses of
      conventional dose regimens merits further evaluation, possibly in a large
      randomized trial.

PMID- 9267484
TI  - Paclitaxel activity in anthracycline refractory breast cancer patients.
AB  - AIMS AND BACKGROUND: We investigated the efficacy and tolerability of two doses
      of paclitaxel, 175 mg/m2 and 135 mg/m2, over a 3-hr infusion, without
      prophylactic G-CSF, in heavily pretreated patients with anthracycline-resistant
      breast cancer. Although paclitaxel may share with anthracyclines a common
      mechanism of drug resistance, there is evidence that the two drugs are not
      completely cross resistant. METHODS: From July 1994 to January 1996, 42 patients
      were treated every 3 weeks, for a maximum of 6 cycles; paclitaxel dose was
      established according to pretreatment extension. RESULTS: In 41 assessable
      patients we observed 9 partial responses, for an overall response rate of 22%
      (95% CI, 10-34%). There was no difference in response rate between the two dose
      levels. Median duration of response was 9 months, median time to progression 5
      months, and median survival 9 months. The dose-limiting toxicity was neutropenia,
      which was grade 3-4 in 40% (135 mg/m2) and 62% (175 mg/m2) of the patients (P =
      0.28); neutropenic fever occurred in 24% of the patients, without significant
      differences between the two dose levels. Other toxicity was mild to moderate.
      CONCLUSIONS: Paclitaxel at doses of 175 mg/m2 or 135 mg/m2 is active and well
      tolerated in advanced breast cancer patients resistant to anthracyclines. The
      prophylactic use of colony-stimulating factors seems appropriate in heavily
      pretreated patients given the higher dose level.

PMID- 9267485
TI  - Intermittent continuous infusion of fluorouracil and low-dose oral leucovorin in
      pretreated breast cancer: a pilot study.
AB  - AIMS AND BACKGROUND: There is evidence that fluorouracil (FU), when administered
      by protracted venous infusion, has antitumor activity in pretreated breast
      cancer. The aims of the study were to assess, in a population of heavily
      pretreated breast cancer patients (> or = 2 lines of chemotherapy previously
      administered), the feasibility and activity of a new combination of oral L
      leucovorin and continuous FU infusion. METHODS: Patients were treated with the
      following combination: oral L-leucovorin, 5 mg/m2 days 1 through 14, plus FU, 250
      mg/m2 days 1 through 14, with cycles repeated every 21 days. RESULTS: Since
      November 1994, 22 patients have entered the study and 20 are assessable for
      response and side effects. Major patient characteristics were: ECOG performance
      status, 0-2; median age, 56 years (range, 41-70); sites of metastasis, bone 9,
      lung 8, liver 2, pleura 7; 2 or more metastatic sites, 18. A total of 74 cycles
      has been administered (median/patient, 3 cycles). Five partial remissions (25%),
      4 disease stabilizations and 11 disease progressions have been observed. Median
      time to progression was 3 months (range 1.6+). Grade I-II mucositis was observed
      in 8 patients and grade III-IV in 6 patients. Other side effects have included
      diarrhea and thrombocytopenia. CONCLUSIONS: The schedule has demonstrated
      moderate activity in heavily pretreated breast cancer, with mucositis as the dose
      limiting toxicity.

PMID- 9267486
TI  - Lack of prognostic value of p53 protein expression in node-negative breast
      cancer.
AB  - AIMS AND BACKGROUND: The association of p53 protein accumulation and prognosis in
      node-negative breast cancer patients has been alternately demonstrated and denied
      in literature reports, and opinions on the use of p53 expression as an indicator
      of high risk of recurrence and as a guide for adjuvant therapy are controversial.
      STUDY DESIGN: The association of p53 protein accumulation with prognosis was
      retrospectively evaluated in a series of 221 node-negative breast cancer patients
      treated with surgery alone and followed up for a minimum of 10 years. p53
      accumulation was determined by immunohistochemistry on archive material, and
      classified into four grades of increasing immunostaining. RESULTS: No association
      was observed between p53 and age or pT category, whereas a significant
      association with nuclear grade was found (P = 0.0014). Univariate and
      multivariate analysis of 10-yr disease-free and overall survival showed a
      significant and independent prognostic association for tumor size (pT category)
      and nuclear grading but not for p53 expression, whatever grade grouping was used.
      CONCLUSIONS: We did not find any evidence supporting the use of p53
      immunostaining in current practice as an independent prognostic indicator or as a
      discriminant factor for adjuvant treatment of node-negative breast cancer
      patients.

PMID- 9267487
TI  - The use of MAB 1977 monoclonal antibody for the immunohistochemical localization
      of beta 1 integrins in paraffin-embedded human kidney.
AB  - AIMS AND BACKGROUND: Integrins are widely known cell membrane receptors for
      extracellular matrix molecules. The beta 1 integrin subgroup is mainly expressed
      by kidney cells; immunolocalization of these molecules is usually carried out on
      cryostatic sections. A commercial monoclonal antibody directed against the human
      beta 1 integrin was tested in order to design a method for the detection of this
      antigen in formalin-fixed, paraffin-embedded human kidney tissue. METHODS:
      Specimens obtained from nephrectomies were fixed with 10% formalin and embedded
      in paraffin. Three different detection protocols were applied after incubation
      with the anti-human beta 1 integrin monoclonal antibody (MAB 1977): 1)
      immunoperoxidase with labeled streptavidin biotin (LSAB), using biotinylated
      secondary antibodies, peroxidase-labeled biotin-streptavidin, and 3,3'
      diaminobenzidine tetra-hydrochloride (DAB) as the revealing system; 2)
      immunoperoxidase with tyramide signal amplification (TSA), using biotinylated
      secondary antibodies, streptavidin-peroxidase, tyramide, streptavidin-peroxidase
      again and DAB; 3) indirect immunofluorescence with fluorescein-labeled anti-mouse
      immunoglobulins. RESULTS: The beat results were obtained with the LSAB detection
      protocol preceded by a predetection step with proteinase k. Proteinase k
      pretreatment did not significantly damage the tissue morphology and successfully
      unmasked beta 1 integrin antigens. Nonspecific background staining was reduced by
      a blocking step with swine serum. Similar results were obtained with the TSA
      detection method; however, although lower concentrations of anti-beta 1 integrin
      immunoglobulins and of secondary biotinylated antibody were employed, there was
      more undesired background staining than with the LSAB protocol. CONCLUSIONS: The
      method reported and discussed here may represent a valid tool for research and
      diagnostic applications based upon detection of beta 1 integrin in paraffin
      embedded human tissues.

PMID- 9267488
TI  - The role of fluorine-18-deoxyglucose (FDG) positron emission tomography (PET)
      whole body scan (WBS) in the staging and follow-up of cancer patients: our first
      experience.
AB  - We report the results of FDG PET whole body scan in 75 cancer patients in whom
      tumor extent was defined by surgical, histological or cytological findings and
      clinical follow-up. Twenty-five had malignant lymphomas, 24 lung carcinomas, and
      26 other types of solid tumors. Twenty-three patients were evaluated at disease
      onset, before therapy, and 37 at the moment of tumor recurrence; the remaining 15
      patients were in complete remission after treatment and were taken as controls.
      Visual and quantitative PET results were compared with conventional imaging (US,
      CT scan and/or MRI, and Tc99m MDP bone scan). In the 60 patients with active
      disease, PET as well as conventional imaging were able to locate the primary
      tumor in all 23 patients studied at disease onset. However, with regard to lymph
      node and distant metastases, PET provided the same information as conventional
      imaging in 31 cases (51.6%), but revealed further neoplastic foci in 29 cases
      (48.4%), 21 in lymph nodes and 8 at distant sites. The sensitivity of PET, in
      comparison with conventional imaging, was 100% versus 100% for the detection of
      the primary tumor, 97.6% versus 55.8% for the localization of node metastases,
      and 100% versus 55.5% for the visualization of distant metastases. The
      specificity, calculated in the group of 15 disease-free patients, was 100% for
      PET and 86.6% for conventional imaging. The therapeutic approach was modified in
      12 patients (20%) on the basis of the PET results. Furthermore, in 14 cases
      (23.3%) with advanced disease, PET provided complete information on tumor spread,
      otherwise obtainable only by taking together the results of all other diagnostic
      procedures. Our data indicate a higher accuracy of FDG PET whole body scan
      compared to conventional imaging techniques in the evaluation of metastatic
      spread both at initial diagnosis and during follow-up, with an important impact
      on therapeutic decision-making. Moreover, by providing complete information on
      tumor spread in some cases, PET can become a profitable tool in terms of cost
      reduction.

PMID- 9267489
TI  - Relationship between cathepsin-D and other prognostic factors in human breast
      cancer.
AB  - Cathepsin-D (CATH-D) is a lysosomal protease induced by estrogens in estrogen
      receptor-positive breast cancer call lines and constitutively produced by
      estrogen receptor-negative breast cancer cells. The concentration of CATH-D in
      the cytosol of 97 human breast tumor tissues was correlated with other well-known
      prognostic factors for human breast cancer. CATH-D was significantly higher in
      node-positive than in node-negative tumors (P = 0.042, Kruskal-Wallis test).
      However, no correlation was found between enzyme levels and the number of
      positive nodes. CATH-D concentration did not correlate with age, menopausal
      status, clinical stage of the disease, size of the primary tumor, steroid
      receptors, thymidine labeling index, histological grade, nuclear grade or
      cellularity. CATH-D did not show any association with the known prognostic
      factors evaluated in this study and its association with lymph nodes was only
      weak.

PMID- 9267490
TI  - Flow cytometric and immunohistochemical correlations in high incidence human
      solid tumors.
AB  - 475 patients with carcinoma at different sites (141 colon-rectum; 102 breast; 50
      stomach; 48 kidney; 46 head and neck; 41 bladder; 47 other sites) submitted to
      surgery have been analyzed after histopathological staging and grading, by flow
      cytometry (monoparametric DNA content analysis) and immunohistochemistry (p53, c
      erbB-2, and PCNA expression). In breast cancer patients the presence of receptors
      for estrogen (ER) and progesterone (PGR) has also been determined. Flow cytometry
      derived parameters were DNA ploidy, fraction of cells in S-phase (SPF), and DNA
      content heterogeneity (multi-clonal stem cell lines with different DNA index
      and/or more than one subpopulations with different ploidy levels in different
      samples from the same tumor). Correlations of the results obtained by the
      different techniques have been attempted by the non-parametric Spearman's rank
      correlation approach. Significant associations (P < 0.05) were found between the
      histopathological, immunohistochemical and flow cytometric parameters considered
      in some anatomical regions, such as stomach (p53 vs DNA content aneuploidy and vs
      heterogeneity), colon-rectum (TNM vs p53 and vs heterogeneity), bladder (grading
      vs DNA content aneuploidy and vs heterogeneity). Tumor heterogeneity proved to be
      dependent on the number of tumor samples taken. The results of this preliminary
      assessment will subsequently be compared with the data obtained from a currently
      ongoing follow-up survey.

PMID- 9267491
TI  - Endoductal tissue sampling of biliary strictures through endoscopic retrograde
      cholangiopan creatography (ERCP).
AB  - AIM AND BACKGROUND: Pathological proof of malignant in biliary strictures is
      useful in the preoperative setting as it helps define therapeutic planning and
      prognosis, and reduces the length of the subsequent surgical intervention.
      However, it is difficult to obtain. The aim of this study was to evaluate the
      yield of histological and cytological examination of endobiliary samples obtained
      during endoscopic retrograde cholangiopancreatography (ERCP). METHODS:
      Endobiliary forceps biopsy and brush cytology were performed during ERCP
      examination in 52 consecutive patients, 36 with malignant and 16 with benign
      strictures. RESULTS: Histology and cytology turned out to have the same
      sensitivity (53%). The gain in sensitivity achieved by combining the two
      techniques was limited, reaching a value of 61%. The specificity, however, was
      100% for both methods. Most of the few complications observed were due to
      sphincterotomy and subsided spontaneously or with medical treatment. However, one
      patient experienced a serous complication and chose to be treated by surgical
      intervention. The complication was caused by forceps biopsy. CONCLUSIONS: This
      study shows that 1) sampling of biliary strictures during ERCP is the primary
      approach to tissue diagnosis; 2) brush cytology alone is sufficient in clinical
      practice; 3) forceps biopsy must always be used to sample intra-ampullary
      strictures but should be considered as a secondary step to sample strictures
      located more proximally, in the bile ducta, if previous cytology was negative.

PMID- 9267492
TI  - Malignant stromal tumor consistent with fibrosarcoma arising from Meckel's
      diverticulum. Clinicopathological study of an incidentally discovered tumor and
      review of the literature.
AB  - The authors report a case of a Meckel's diverticulum mesenchymal tumor
      incidentally discovered in a 69-year-old woman undergoing laparotomy for an
      ovarian cyst. Histological examination of the tumor revealed a fasciculated
      proliferation of spindle cells that proved to be immunoreactive to vimentin only;
      pleomorphism was mild, necrosis extensive and mitotic count high. Because these
      features were consistent with those of fibrosarcoma, the tumor was classified in
      the category of gastrointestinal stromal tumors; more specifically, it was
      considered malignant for the presence of spread beyond the primary site in the
      form of peritoneal nodules and for the high mitotic count. We have been able to
      find only one previously reported case of mesenchymal malignant tumor of Meckel's
      diverticulum classified as fibrosarcoma among the 199 malignant tumors described
      in the literature. Based on this personal experience and on the review of the
      literature concerning malignant tumors of Meckel's diverticulum, we discuss both
      the rarity of these tumors and the importance of removing Meckel's diverticulum
      every time it is found during laparotomy.

PMID- 9267494
TI  - Granular cell basal cell carcinoma of the skin. Report of a case with
      immunocytochemical positivity for lysozyme.
AB  - Granular cell tumors have been described in many sites throughout the body. To
      our knowledge, few cases have been described in the literature. We report here
      the sixth case, in which positivity for lysozyme was also observed for the first
      time. The problems of the histogenesis and differential diagnosis of this rare
      variant of basal cell carcinoma are also discussed.

PMID- 9267493
TI  - Antineuronal antibody in a patient with neuroblastoma and opsoclonus-myoclonus
      ataxia: a case report.
AB  - We describe a case of a patient with neuroblastoma and opsoclonus- myoclonus
      ataxia displaying serum and CSF anti-Hu antibodies that were able to recognize
      antigens of the patient's own tumor.

PMID- 9267495
TI  - Multiple tumor case: report and analysis of an autopsy case.
AB  - An interesting multiple tumor case is described in which 4 different kinds of
      tumors were diagnosed in the same patient at autopsy and histopathologic
      examination. The tumors were the following: 1) prolactinoma of the anterior
      pituitary lobe; 2) basal cell carcinoma of the nose; 3) adenocarcinoma of the
      colon sigmoideum; 4) multiple oncocytomas (oncocytomatosis) in the kidneys.
      Immunohistochemical investigation for p53 revealed a strong intranuclear
      positivity in the colonic carcinoma cells as a result of the overexpression of a
      possible mutant type of the protein. The other 3 tumors were negative with the
      p53-specific DO-7 antibody, therefore, no point mutation was thought to be
      present in the p53 gene of the tumor cells. The immunohistochemical and
      anamnestic data suggested that this is not a hereditary syndrome, and there is no
      common pathogenesis of these tumors. Its rarity is interesting in our case
      because of the coincidence of 4 different unrelated tumors and the absence of
      anamnestic data for familial accumulation or predisposition for multiple tumors.

PMID- 9267496
TI  - Temporomandibular joint metastasis from rectal carcinoma: CT findings before and
      after radiotherapy. A case report.
AB  - Metastatic disease to the masticator space and to the jaws is a rare event. About
      a dozen cases are reported in the current literature. We describe the imaging
      findings of a rectal adenocarcinoma metastatic to the temporomandibular joint
      before and after radiotherapy.

PMID- 9267497
TI  - Radiation-induced sarcoma following curative radiotherapy for testicular
      seminoma: case report and brief review of the literature.
AB  - We report a case of radiation-induced retroperitoneal leiomyosarcoma which
      developed 37 years after the patient received radiation therapy for testicular
      seminoma. The sarcoma originated within the para-aortic field, extensively
      involving neighboring organs, soft tissue and muscle tissues, and could be only
      partially resected. The absolute number of these secondary sarcomas is low, but
      the risk of developing such neoplasms calls for awareness in the long-term follow
      up of cured seminoma patients.

PMID- 9267498
TI  - Questions regarding complications of early versus standard-age gonadectomies.

PMID- 9267499
TI  - Medical epistemology for food animal veterinarians.

PMID- 9267500
TI  - What is your diagnosis? Portocaval and portoazygous shunts and microhepatia in a
      dog.

PMID- 9267501
TI  - Results of the 1997 AVMA survey of US pet-owning households regarding use of
      veterinary services and expenditures.

PMID- 9267502
TI  - Economic evaluation of risks to producers who use milk residue testing programs.
AB  - OBJECTIVE: To evaluate the decision to test for milk antimicrobial residues in
      milk from dairy cows treated with procaine penicillin G (PPG). DESIGN: Economic
      decision analysis after stochastic simulation. SAMPLE POPULATION: 1,000 computer
      simulated cows/model. PROCEDURE: Meta-analysis of the Food Animal Residue
      Avoidance Databank was used to generate PPG disappearance curves for cows given
      single PPG treatments, IM, of 6,600 U/kg (3,000 U/lb) of body weight or 26,400
      U/kg (12,000 U/lb), and multiple treatments at 26,400 U/kg (12,000 U/lb), IM.
      These curves were entered into 1,000-replication stochastic pharmacokinetic
      models, generating population-level milk PPG profiles for each treatment group
      for each day after treatment, which were subjected to economic-decision analyses
      of feasibility of residue testing. The model was evaluated for changes in herd
      size, proportion of herd available for testing, milk production, test price, test
      sensitivity/specificity, and withdrawal periods. RESULTS: For both single
      treatment groups, a 2-day withdrawal period avoided violative residues. However,
      nearly two thirds of the cows risked false identification for violative residues.
      For the multiple-treated group, nearly 40% had violative residues after a 5-day
      withdrawal period, and an additional 10 to 15% risked false identification for
      violative residues. Economic analysis yielded a decision against testing; mean
      cost was $2 (ie, 5% more than the mean cost of not testing). CLINICAL
      IMPLICATIONS: Complex dynamics of current milk residue tests discourage
      practitioners from recommending procedures to clients. In general, increases in
      herd size, milk production, proportion of a herd available for testing, or milk
      price will increase the value of testing. Increasing test sensitivity decreases
      its desirability to producers.

PMID- 9267503
TI  - Results of a survey to assess knowledge and expectations of veterinarians and
      their clients regarding heartworm preventives and vaccinations in dogs.
AB  - OBJECTIVE: To determine the knowledge and expectations of veterinarians and
      clients regarding heartworm preventives and annual vaccinations for dogs. DESIGN:
      Practitioner and client survey. SAMPLE POPULATION: 435 veterinarians and 1,805
      clients. PROCEDURE: A survey was mailed to veterinarians requesting information
      from them and their dog-owning clients on expectations and knowledge regarding
      heartworm preventives and annual vaccinations. Responses of veterinarians were
      compared with those of clients, and both were compared with label indications.
      RESULTS: Expectations of veterinarians and clients regarding heartworm
      preventives were similar and usually were consistent with regulatory
      interpretation of label terms. Of clients purchasing heartworm preventives, 38%
      did not know that the medication was effective against intestinal nematodes.
      Veterinarians and clients would be unsatisfied with a product that reduced, but
      did not eliminate, all intestinal nematodes. Most clients knew that annual
      vaccinations included distemper virus, parvovirus, and rabies virus, but about
      half of them did not know that other antigens were in the vaccines. CLINICAL
      IMPLICATIONS: Effects of heartworm preventives and diseases for which dogs are
      annually vaccinated should be explained fully to clients.

PMID- 9267504
TI  - Comparison of ketoprofen, oxymorphone hydrochloride, and butorphanol in the
      treatment of postoperative pain in dogs.
AB  - OBJECTIVE: To compare analgesic effects of ketoprofen, oxymorphone hydrochloride,
      and butorphanol when used to control postoperative pain associated with elective
      orthopedic surgery in dogs. DESIGN: Prospective randomized clinical trial.
      ANIMALS: 70 dogs undergoing orthopedic surgery on a hind limb. PROCEDURE: Dogs
      were randomly assigned to 1 of 4 postoperative analgesic treatment groups:
      ketoprofen alone, oxymorphone alone, butorphanol alone, or ketoprofen
      oxymorphone. Drugs were given IM at the end of anesthesia. Pain score, sedation
      score, arterial blood pressures, arterial blood gas partial pressures, and plasma
      cortisol concentration were measured for 12 hours after surgery. If the pain
      score was > or = 9, supplemental oxymorphone was administered IM. RESULTS: The
      proportion of dogs that did not require supplemental treatment with oxymorphone
      was significantly higher for the ketoprofen alone and ketoprofen-oxymorphone
      groups than for the oxymorphone alone group. During the first hour after surgery,
      pain score was lower for oxymorphone alone and ketoprofen-oxymorphone groups than
      for ketoprofen or butorphanol alone groups. Significant differences were not
      detected among groups in regard to pain score 2 and 3 hours after surgery or in
      regard to arterial blood pressures at any time. From 4 to 12 hours after surgery,
      pain score was significantly lower for the ketoprofen alone group than for other
      groups. Plasma cortisol concentration was significantly higher for the
      oxymorphone alone group 6 and 8 hours after surgery, compared with other groups.
      CLINICAL IMPLICATIONS: Except during the first hour after surgery, dogs given
      ketoprofen alone after elective orthopedic surgery had a greater level of, and
      longer-lasting, analgesia than did dogs given oxymorphone or butorphanol alone.

PMID- 9267505
TI  - Surgical treatment of dacryocystitis caused by cystic dilatation of the
      nasolacrimal system in three dogs.
AB  - A 4-year-old castrated male Golden Retriever was referred for evaluation of
      intermittent purulent discharge from the right eye of 4-months' duration. A
      radiolucent area in the maxillary bone was detected on examination of skull
      radiographs. Dacryocystorhinography revealed pooling of contrast material in the
      radiolucent area. A rhinotomy was performed, and a large opening between the
      cystic structure of the nasolacrimal system and the nasal cavity was created.
      Epiphora resolved after surgery and had not recurred by 9 months after surgery.
      Two other dogs had cystic structures of the nasolacrimal system and were treated
      surgically to allow drainage into the nasal cavity.

PMID- 9267506
TI  - Traumatic separation of the annular cartilage from the external auditory meatus
      in a cat.
AB  - A 13-year-old cat was evaluated because of anorexia and otic discharge of 1
      week's duration. A left head tilt and left facial nerve deficit were evident.
      Pink fleshy tissue was seen in the area where the tympanic membrane was expected
      during otoscopic examination. The left ear canal was laterally displaced from the
      skull on a rostrocaudal (open mouth) radiographic view, suggesting ear canal
      separation. During surgery, the annular cartilage was found to be separated from
      the external auditory meatus, and total ear canal ablation was performed.
      Complications did not develop, and facial nerve function returned 6 weeks after
      surgery. In previous reports, traumatic ear canal separation was diagnosed after
      trapped otic secretions formed abscesses or para-aural fistulas.

PMID- 9267507
TI  - Zinc-responsive dermatosis in northern-breed dogs: 17 cases (1990-1996).
AB  - OBJECTIVE: To determine the response rate of zinc-responsive dermatosis to zinc
      supplementation, the optimal dosage of zinc required for resolution of lesions,
      the rate of recurrence of lesions, and to develop recommendations for maintenance
      dosages of zinc to be administered to dogs with this type of zinc-responsive
      dermatosis. DESIGN: Retrospective case series. ANIMALS: 17 northern-breed dogs
      with a diagnosis of zinc-responsive dermatosis. PROCEDURE: Histologic evaluation
      of skin biopsy specimens and review of medical records. Additional information
      was obtained from veterinarians and owners via a telephone questionnaire.
      RESULTS: In 12 of 17 dogs, lesions were unilateral initially, then became
      symmetrical as the disease progressed. Pyoderma was evident in 5 of 17 dogs,
      whereas 10 were pruritic. Most lesions initially developed between September and
      April, and 12 of 17 dogs developed lesions in February, October, and November.
      Initial dosages of zinc supplement ranged from 0.8 to 4.6 mg/kg of body weight/d
      (0.36 to 2.09 mg/lb/d). Effective/ maintenance dosages ranged from 0.5 mg/kg
      (0.23 mg/lb), twice weekly, to 8.0 mg/kg/d (3.6 mg/lb/d). Fifteen of 17 dogs had
      complete resolution of lesions after zinc supplementation. Lesions recurred in 9
      of 16 dogs. Approximately half of the recurrent lesions were a result of a missed
      dose or a decrease in dosage or frequency of zinc supplementation. CLINICAL
      IMPLICATIONS: An initial dosage of zinc supplement of 1.0 mg of elemental zinc/kg
      (0.45 mg of elemental zinc/lb), PO, every 24 hours is recommended. Treatment
      should be continued for 1 month to determine response to treatment, and the daily
      dosage should be increased by 50% if the initial dosage is not effective. Dogs
      are prone to recurrence of lesions if a dose of zinc is missed or the dosage or
      frequency is decreased.

PMID- 9267508
TI  - Racing-related factors and results of prerace physical inspection and their
      association with musculoskeletal injuries incurred in thoroughbreds during races.
AB  - OBJECTIVE: To describe and compare data from Thoroughbreds that sustained
      musculoskeletal injuries while racing with data from matched control horses.
      DESIGN: Matched case-control study. ANIMALS: 216 Thoroughbreds that sustained a
      musculoskeletal injury while racing and 532 horses from the same races that were
      not injured. PROCEDURE: Data regarding racing history, race-entrant
      characteristics, racing events determined by analysis of videotapes of races, and
      results of prerace physical inspections were determined for all horses. Injured
      horses were compared with control horses by using conditional logistic
      regression. RESULTS: Results of prerace inspection by regulatory veterinarians
      were significantly associated with injury. Odds of musculoskeletal injury, injury
      of the suspensory apparatus of the forelimb, and injury of the tendon of the
      superficial digital flexor muscle of the forelimb were 5.5 to 13.5 times greater
      among horses assessed to be at increased risk of injury by regulatory
      veterinarians on the basis of results of prerace inspection than for horses not
      considered to be at increased risk of injury. Odds of an abnormal finding in the
      suspensory ligament during prerace inspection were 3.4 times greater among horses
      that injured the suspensory apparatus than among control horses, and odds of an
      abnormal finding in the tendon of the superficial digital flexor muscle during
      prerace inspection were 15 times greater among horses that injured the tendon
      than among control horses. CLINICAL IMPLICATIONS: Regulatory veterinarians can
      identify horses during prerace physical inspection that have an increased risk of
      injury during races. Prerace physical inspections could be used to reduce the
      risk of injury to Thoroughbreds during races.

PMID- 9267509
TI  - Adjunctive use of a neodymium:yttrium-aluminum garnet laser for treatment of
      pythiosis granulomas in two horses.
AB  - Pythiosis, caused by Pythium insidiosum, is a common cutaneous granulomatous
      disease in horses. Surgical removal is the most common treatment; however, high
      rates of recurrence have been reported. Results of examination of 2 horses with
      pythiosis granulomas in which a neodymium:yttrium-aluminum-garnet laser was used
      to photoablate the bed after removal are reported. The mass had not recurred in
      either horse 1 year after surgery. Photoablation results in collateral thermal
      necrosis and may kill organisms that have infiltrated surrounding tissues, thus
      reducing the risk of recurrence.

PMID- 9267510
TI  - Effects of parenteral administration of vitamin E on health of periparturient
      dairy cows.
AB  - OBJECTIVE: To determine the effect of administration of vitamin E (D-alpha
      tocopherol) on the incidence of retained placenta, metritis, and clinical
      mastitis during early lactation and on tocopherol concentrations. DESIGN:
      Prospective randomized controlled study. ANIMALS: 420 Holstein cows. PROCEDURE:
      Vitamin E (3,000 mg, IM, once) was administered to 204 cows B to 14 days before
      expected parturition, and 216 control cows were not treated. The number of cows
      that had retained placenta, metritis, clinical mastitis, displaced abomasum, and
      clinically apparent acetonemia or hypocalcemia were recorded. Serum
      concentrations of tocopherol, the tocopherol:cholesterol ratio, and glutathione
      peroxidase activity were determined from samples obtained before administration
      of vitamin E, 7 and 14 days after administration, and at 30 days after
      parturition from 36 treated and 36 control cows. RESULTS: Administration of
      vitamin E significantly decreased the incidence of retained placenta and metritis
      (13/204 [6.4%] and 8/204: [3.9%], respectively, for the vitamin E-treated group;
      27/216 [12.5%] and 19/ 216 [8.8%], respectively, for the untreated group) but did
      not affect the incidence of clinical mastitis. Serum vitamin E concentration was
      significantly higher in treated than in control cattle at 7 and 14 days after
      administration, but serum tocopherol: cholesterol ratio was significantly higher
      only at 7 days after administration. CLINICAL IMPLICATIONS: Parenteral
      administration of a single injection of vitamin E before parturition may decrease
      the incidence of retained placenta and metritis in dairy cows but will increase
      serum concentrations for 7 to 14 days after administration.

PMID- 9267511
TI  - Use of physiologic variables to predict milk yield after clinical mastitis in
      dairy cattle.
AB  - OBJECTIVE: To determine the association between intramammary infections caused by
      various bacteria and hepatic damage, as measured by serum sorbitol dehydrogenase
      (SDH) activity, WBC counts, and PCV and the association of clinical variables
      with milk production after a case of clinical mastitis. DESIGN: Prospective,
      cohort study. ANIMALS: 82 cows with clinical mastitis. PROCEDURE: Information on
      milk production, mastitis status, and selected physiologic variables was
      collected during a 1-year period. Milk samples for bacteriologic evaluation were
      collected on day 1 of an episode of clinical mastitis. Physical examination was
      performed and blood samples for laboratory evaluation were collected on days 1,
      5, and 9. Primary outcome was mature equivalent 305-day (ME305) milk production.
      Correlations were assessed using a multiple regression model. RESULTS: Higher WBC
      counts were associated with higher ME305 values. For cows with coliform mastitis,
      increases in SDH values were associated with higher ME305 values. For cows with
      coliform and streptococci/staphylococci mastitis, PCV was associated with ME305
      values. Higher PCV values were associated with lower ME305 values for
      streptococci/ staphylococci and coliform infections. CLINICAL IMPLICATIONS: The
      association between milk production and WBC count indicated that cows mobilizing
      WBC were better able to neutralize mammary gland infections, which may result in
      better milk production. The association between milk production and PCV suggested
      that maintaining hydration in cows with clinical mastitis may be a critical
      aspect of treating all cows with mastitis.

PMID- 9267512
TI  - An overview on chemical modification of enzymes. The use of group-specific
      reagents.
AB  - Chemical modification is an important approach to the study of enzyme active
      sites. This article presents an overview of the methods used. The basic concepts,
      applications and limitations of chemical modification are outlined. The use of
      reagents specific for different amino acid side chains is also discussed.

PMID- 9267513
TI  - Chemical modification of enzymes: kinetic aspects.
AB  - Important information on enzyme ligand interactions can be obtained when
      analyzing the kinetics of chemical modification reactions. In this article,
      several kinetic models of inactivation are discussed, along with the
      determination of enzyme-ligand dissociation constants and of the pK of enzyme
      reactive groups from chemical modification kinetic data.

PMID- 9267514
TI  - Affinity labels as probes for the study of the nucleotide binding site of
      enzymes.
AB  - Affinity labeling has proved to be a very useful tool for searching important
      amino acid residues located in active or allosteric sites of enzymes. In this
      article, the general principles and specific examples of the use of affinity
      labeling are discussed.

PMID- 9267515
TI  - Photoaffinity labeling and photoaffinity crosslinking of enzymes.
AB  - Photoaffinity labeling is a special type of chemical modification, where the
      label is activated by the action of light. This article presents the general
      principles and limitations of this technique, its application to the study of
      Micrococcus luteus ATPase and the use of photoaffinity crosslinking to probe the
      structure of this enzyme.

PMID- 9267516
TI  - Chemical modification of allosteric properties of enzymes.
AB  - Chemical modification is usually employed to study enzyme active sites. Valuable
      information can also be obtained, however, when this technique is used to probe
      allosteric sites. This approach is discussed in this article, and it is
      exemplified in chemical modification studies of the allosteric enzyme
      phosphofructokinase.

PMID- 9267517
TI  - Sensitized photo-oxidation of amino acids in proteins: some important biological
      implications.
AB  - The sensitized photo-oxidation of amino acids in proteins is a special case of
      chemical modification, which is used in particular to study buried and exposed
      groups in proteins. The general principles of the technique and various
      applications of it are discussed in this article.

PMID- 9267518
TI  - The study of the catalytic sites of enzymes using fluorescent compounds.
AB  - The use of fluorescent compounds can be a valuable tool to probe the active site
      of enzymes. Several examples of this approach are discussed, particularly the use
      of pyridoxal phosphate analogs. The study of protein-protein interactions by
      means of fluorescent-labeled proteins is also analyzed.

PMID- 9267519
TI  - Active-site studies of enzymes by secondary structure prediction and by molecular
      modeling.
AB  - Since the determination of the tertiary structure by X-ray crystallography has
      been achieved only for a limited number of proteins, alternative approaches are
      being sought. In this article, the use of secondary structure prediction and of
      molecular modeling is discussed. Several examples are analyzed in detail.

PMID- 9267520
TI  - Active-site studies of enzymes by X-ray diffraction methods.
AB  - X-Ray diffraction is the only method currently available for the determination of
      the detailed three-dimensional structure of macromolecules. In this article, the
      principles behind the use of X-ray crystallography in the study of protein
      structure are presented. The results obtained in its application to several
      enzymes are discussed, as well as the limitations of the method.

PMID- 9267521
TI  - Protein engineering as a powerful tool for the chemical modification of enzymes.
AB  - This article discusses the techniques of site-specific mutagenesis and protein
      engineering and their application in the study of enzyme active sites and the
      mechanism of enzyme action. Particular emphasis is given to beta-lactamase.

PMID- 9267522
TI  - Applications of nuclear magnetic resonance to determine the structure and
      interactions of ligands, peptides and enzymes.
AB  - Nuclear magnetic resonance (NMR) spectroscopy is emerging as a powerful tool for
      the study of enzyme structure and function. This article discusses the general
      principles of NMR and the potential information this technique can provide in the
      study of enzymes along with its limitations.

PMID- 9267524
TI  - Acute ethanol intoxication suppresses the pulmonary inflammatory response in rats
      challenged with intrapulmonary endotoxin.
AB  - The effects of acute ethanol intoxication on the functional activities of
      circulating and lung-recruited polymorphonuclear leukocytes (PMNs) and alveolar
      macrophages (AMs) were determined in rats challenged with intratracheal endotoxin
      to elucidate the mechanisms underlying the defects of pulmonary host defenses
      caused by acute ethanol intoxication. Acute ethanol Intoxication was induced by
      an intraperitoneal injection of 20% ethanol at a dose of 5.5 g of ethanol/kg. The
      control animals were injected with an equal amount of saline. Thirty min after
      intraperitoneal injection, rats were challenged with intratracheal endotoxin (300
      micrograms/kg in 0.5 ml of saline) or saline. The rats were killed 3 h after
      intratracheal injection. CD11b/c expression on PMNs and phagocytosis and hydrogen
      peroxide generation of PMNs and AMs were determined by flow cytometry. Cytokine
      Induced neutrophil chemoattractant (CINC) level in bronchoalveolar lavage fluid
      was measured with a specific ELISA. Intratracheal endotoxin caused a significant
      PMN recruitment into the lung in control animals. Acute ethanol intoxication
      completely suppressed the endotoxin-induced pulmonary recruitment of PMNs.
      Pulmonary-recruited PMNs exhibited a significant upregulation (8-fold) of CD11b/c
      expression when compared with circulating PMNs. This upregulation of CD11b/c
      expression was abolished by ethanol intoxication. Ethanol intoxication suppressed
      hydrogen peroxide generation by AMs and lung-recruited PMNs, and the phagocytosis
      of circulating PMNs. In contrast, acute ethanol intoxication did not affect
      pulmonary CINC production. These data indicate that the antiinflammatory effects
      of alcohol seem to be primarily based on the effects of ethanol on the PMNs
      themselves and not on the generation of certain chemotactic stimuli. In addition
      to the impairment of PMN recruitment, the suppression of AM and PMN activities
      also contributes to the mechanisms underlying ethanol-induced defects of
      pulmonary host defenses.

PMID- 9267523
TI  - Quick method for confirmation of quantitative trait loci.
AB  - Numerous algorithms for the identification and genetic mapping of quantitative
      trait loci (QTL) have been developed. Methods for confirming QTL maps involve
      either examination of independent segregating populations or the construction of
      congenic lines differing only in the QTL of interest. Because these projects
      require a minimum of several years or thousands of marker assessments in
      laboratory mice, an alternative, faster congenic method has been proposed. In a
      preliminary study, we tested this method for confirming QTLs identified in
      crosses between the ILS and ISS selected lines of mice for differential
      sensitivity to the hypnotic effects of ethanol. Herein, we report the
      construction of "segregating congenic" strains in which each QTL is made
      homozygous in a single generation, whereas the remainder of the genetic
      background is allowed to segregate. Sensitivity to ethanol among the progeny of
      such mice is consistent with predictions. Phenotypic variation is high, as
      expected, due to the background segregation, and statistical significance was
      attained in only 2 of 7 comparisons. Such segregating congenic populations may be
      a valuable research tool for confirming QTL map positions and for subsequent
      assessment of individual pathways and mechanisms of action of individual QTLs.

PMID- 9267525
TI  - Acute ethanol administration modulates leukocyte actin polymerization in
      endotoxic rats.
AB  - The effects of acute ethanol intoxication with or without endotoxemia were
      studied on chemoattractant-initiated actin polymerization in circulating and
      liver-recruited neutrophils [polymorphonuclear leukocytes (PMNs)] and Kupffer
      cells of age-matched male and female rats. In female rats, F-actin content in
      response to f-Met-Leu-Phe in circulating PMNs was significantly upregulated by
      ethanol+endotoxin (ET) treatment relative to saline+ET-treated animals. Male rats
      did not show this upregulated response. In liver-recruited PMNs, the F-actin
      response did not change significantly due to ethanol + ET treatment in cells of
      either gender. The actin polymerization response in Kupffer cells was smaller
      than in liver sequestered PMNs and also exhibited a gender difference. In Kupffer
      cells of female rats, only ethanol+ET treatment elicited an F-actin response to f
      Met-Leu-Phe, whereas in cells of male rats similar increases in F-actin content
      were observed in both saline+ET and ethanol+ET groups. We conclude that ethanol
      enhanced actin polymerization in rats is associated with gender differences. This
      may be one of the underlying mechanisms resulting in upregulated leukocyte
      activation in acutely ethanol-intoxicated endotoxic animals.

PMID- 9267526
TI  - Increased ethanol self-administration after a period of imposed ethanol
      deprivation in rats trained in a limited access paradigm.
AB  - A predominant feature in human alcohol abuse is the reported desire or "craving"
      to consume ethanol along with frequent episodes of drinking after periods of
      abstinence. These and other factors may be responsible for relapse to
      uncontrolled ethanol drinking. When relapse occurs after a period of abstinence,
      ethanol drinking has been shown to be temporarily increased. Two aspects of drug
      dependence could contribute to these increases. One may be the development of a
      need state; the other may involve changes in the perception of the positive
      reinforcing effects of ethanol when reinforcer access is limited. To investigate
      this phenomenon further, the present study was conducted to examine in
      nondependent rats the effect of forced time-off on oral ethanol self
      administration in a limited access paradigm (30 min/day). Male Wistar rats were
      trained to respond for ethanol (10% w/v) or water in a two-lever, free-choice
      condition using a saccharin fading procedure. After the establishment of stable
      baseline responding for ethanol, various ethanol deprivation periods (3, 5, 7,
      14, or 28 days) were imposed, during which no ethanol was available. Responding
      for ethanol increased as a function of the duration of the deprivation period
      when compared with baseline levels. This increase was temporary and returned to
      baseline levels within 2 to 3 days. Given that the shortest time-off period was 5
      days and the rats showed no signs of withdrawal, this transient increase in
      ethanol responding does not seem to be related to the manifestation of dependence
      and withdrawal, and may be related to changes in ethanol's reinforcement
      properties. These results with rats may provide a useful tool to elucidate
      mechanisms underlying human alcohol seeking behavior and relapse.

PMID- 9267527
TI  - Studies on the time-course of ethanol's acute effects on skeletal muscle protein
      synthesis: comparison with acute changes in proteolytic activity.
AB  - A study of the effects of ethanol on skeletal muscle protein synthesis and
      protease activities was carried out in young male Wistar rats (150 g) for up to
      24 hr after a single intraperitoneal dose of 75 mmol of ethanol/kg of body
      weight. At 20 min, the mean blood ethanol levels were 448 mg/dl. This level
      dropped steadily to zero through the following 24 hr. Compared with pair-fed
      controls, significant reductions in total protein, RNA, and DNA contents were
      seen only after 24 hr in all skeletal muscles studied: changes were more marked
      in the muscles containing large proportions of type II fibers. In plantaris
      muscle, the fractional rate of protein synthesis (ks, %/day) did not fall 20 min
      after dosage but was reduced after 1 hr by 23% (p < 0.001), and by 63% after 24
      hr, compared with control saline-injected rats (p < 0.001). This effect was
      independent of dietary intake because, compared with the pair-fed group, the 24
      hr ethanol-treated rats still showed a 52% decrease in fractional rates of
      protein synthesis (p < 0.001). Smaller reductions in ks were seen in soleus
      muscles in response to ethanol at 24 hr (-39%, p < 0.001). The activities of a
      variety of lysosomal and nonlysosomal proteases in plantaris muscle of 24-hr
      treated rats were not significantly affected by ethanol. Only alanyl- and
      tripeptidyl-aminopeptidase activities were reduced significantly (26%, p < 0.05
      and 39%, p < 0.01, respectively). These results suggest that the muscle
      compositional changes seen over acute periods of ethanol toxicity are
      predominantly associated with impaired synthesis of protein and that the
      contribution of cellular proteolytic systems may be minimal. The effects of
      ethanol on skeletal muscle protein metabolism are greater in muscles containing a
      predominance of type II fibers than in those containing mainly type I fibers.
      Ethanol's effects on muscle may be influenced by hormonal changes after 24 hr,
      because protein synthesis is still compromised and free plasma T3 and
      corticosterone are altered at this time-point.

PMID- 9267528
TI  - Evaluation of lactational parameters after alcohol administration for four days
      during early or midlactation in the rat.
AB  - This study was conducted to examine the effects of alcohol administered for 4
      days during early lactational (days 5 to 8; experiment I) or midlactational (days
      9 to 12; experiment II) stage in the rat on various lactational parameters.
      Litter size was adjusted to eight on day 2, and dams were implanted with an
      atrial catheter on day 3 (experiment I) or day 7 (experiment II). From days 5 to
      8 in experiment I and days 9 to 12 in experiment II, dams were infused with
      saline (control rats) or alcohol in saline solutions (1.0 and 2.0 g/kg body
      weight; experimental groups). Blood alcohol levels (BALs) achieved after infusion
      of the initial doses were maintained for 4 hr daily by continuing infusion. To
      control for the reduced food intake in the high dose alcohol group, one control
      group and the group given 1.0 g/kg of body weight alcohol were pair-fed to the
      2.0 g/kg body weight alcohol group. On day 8 (experiment I) or day 12 (experiment
      II), pups were separated from the dam at 0800 hr, and an extension was attached
      to the catheter. Alcohol or saline was infused, and the BALs achieved after
      infusion of initial doses were maintained for 4 hr. After removal of a baseline
      blood sample, pups were returned to dams, and additional blood samples were taken
      for prolactin measurement 10, 30, 60, and 120 min after suckling started.
      Suckling latency and milk consumed during the 120 min of suckling were measured.
      Litters were weighed every other day from days 2 to 21. In both studies, suckling
      induced prolactin was inhibited by alcohol. Milk consumed by the pups during the
      2-hr period was lower for alcohol groups, compared with control. The suckling
      latencies were comparable among groups. Litter weights showed no alcohol dose
      effect. In summary, based on the results from our previous and present studies,
      we conclude the following: alcohol administered for 1, 4, or 8 days inhibited
      suckling-induced prolactin release in lactating rats. During a 2-hr test period
      after alcohol administration, milk consumed by pups was not adversely affected
      after alcohol administration for 1 day. Whereas, 4 or 8 days of administration
      had a significant effect. The adverse effect of alcohol on litter growth,
      however, was evident only after 8 days of alcohol administration. Thus, the
      detrimental effects of alcohol on different lactational parameters seem to be
      correlated to the duration of alcohol administration to dams during lactation.

PMID- 9267529
TI  - Dexmedetomidine, diazepam, and propranolol in the treatment of ethanol withdrawal
      symptoms in the rat.
AB  - In this study, the effects of dexmedetomidine, a selective alpha 2-adrenoceptor
      agonist, on ethanol withdrawal symptoms, were compared with those of diazepam and
      propranolol. The rats were given highly intoxicating doses of ethanol for 4 days.
      After the intoxication period, rats were divided into four equal groups: a
      dexmedetomidine-treated group (30 micrograms/kg, sc), a diazepam-treated group (2
      mg/kg, sc), a propranolol-treated group (5 mg/kg, sc), and a control group with
      no medication. Medication was given in the withdrawal phase-2, 8, 14, and 20 hr
      after the onset of the withdrawal symptoms. The severity of the ethanol
      withdrawal symptoms (rigidity, tremor, irritability, and hypoactivity) was
      observed up to 33 hr after the onset of the ethanol withdrawal symptoms. Both
      dexmedetomidine and diazepam significantly relieved tremor compared with the
      control group. Diazepam reduced irritability significantly, compared with the
      control group. When measured as the sum score of the three most specific
      withdrawal signs (rigidity, tremor, and irritability), dexmedetomidine and
      diazepam significantly relieved the ethanol withdrawal reaction. Propranolol
      attenuated tremor, but was inefficient against other withdrawal symptoms.
      Dexmedetomidine may thus represent a new effective drug in the treatment of the
      ethanol withdrawal syndrome.

PMID- 9267530
TI  - Alcohol consumption by young actively growing rats: a study of cortical bone
      histomorphometry and mechanical properties.
AB  - Alcohol consumption by young actively growing rats has been previously
      demonstrated to decrease cortical and cancellous bone density, to reduce
      trabecular bone volume, and to inhibit bone growth at the epiphyseal growth
      plate. This study addresses the action of alcohol on cortical bone growth using
      histomorphometric techniques and on mechanical properties by three-point bending.
      Four-week-old, female Sprague-Dawley rats were divided into three groups. Alcohol
      treated animals were fed a modified Lieber-DeCarli diet ad libitum containing 35%
      ethanol-derived calories, whereas the pair-fed animals (weight-matched to ethanol
      rats) received an isocaloric liquid diet in which maltose-dextrin-substituted
      calories were supplied by ethanol. Chow animals were fed a standard rat chow ad
      libitum. Femora were removed for analysis after 2, 4, 6, or 8 weeks on the diets.
      Cortical bone area, bone formation rates, and mineral apposition rates were
      reduced in the alcohol-fed animals. Bone stiffness, strength, and energy absorbed
      to fracture were significantly lower in the alcohol-fed animals. This distinctive
      alcohol effect was revealed to be caused by lower quality bone tissue as
      reflected by lower elastic moduli and yield strengths.

PMID- 9267531
TI  - Effects of time-of-day and photoperiod phase shifts on voluntary ethanol
      consumption in rats.
AB  - Two experiments were conducted to examine the circadian fluctuations in voluntary
      ethanol (ETOH) consumption in male Sprague-Dawley rats conditioned to consume
      ETOH in their homecage and exposed to photoperiod phase shifts equivalent to
      those experienced by humans. Using a maintenance concentration of 20% w/v ETOH,
      changes in homecage drinking in 42 rats were assessed after photoperiod phase
      shifts similar to those inducing "jet lag" in humans and after experimenter
      induced "hangover." A single 8-hr photoperiod phase advance significantly
      increased ETOH intake for three consecutive days, and a single photoperiod phase
      delay increased intake only on the day of the phase shift. Acute ETOH withdrawal
      significantly reduced the voluntary consumption of ETOH for two consecutive days.
      In a second group of 30 rats maintained to consume a lower concentration of 10%
      w/v ETOH, the long-term effects of "shift lag" initiated by repeated photoperiod
      phase shifting similar to those experienced by humans working under a rotating
      work schedule were examined. Significant increases in intake occurred over the 2
      month testing period. The significant alterations in voluntary intake initiated
      by the shift work schedule was related to the significant changes in blood
      alcohol concentrations.

PMID- 9267532
TI  - Effect of fetal ethanol exposure on the in vitro release of growth hormone,
      somatostatin and growth hormone-releasing factor induced by clonidine and growth
      hormone feedback in male and female rats.
AB  - This study was designed to examine the effect of fetal ethanol (ETOH) exposure on
      the sensitivity of the hypothalamic-growth hormone (GH) axis to clonidine (an
      alpha 2-adrenoreceptor agonist) stimulation and GH feedback. During gestation,
      dams were fed either a liquid diet in which 36% of the calories were derived from
      ETOH, or pair-fed an isocaloric control liquid diet without ETOH. A second set of
      controls were fed lab chow ad libitum. After birth, offspring of ETOH-fed dams
      were cross-fostered to a separate group of ad libitum control dams. The
      hypothalami and pituitaries of 10-, 20-, 30-, and 50-day-old offspring were
      separated by age, diet, and sex; pooled 6 to 8 per chamber; and tested in a
      hypothalamic-pituitary coperifusion system. Chambers were perifused with either
      clonidine (2 x 10(-8) M) alone, which mimics the endogenous trigger for GH
      release, or clonidine in combination with human GH (2 x 10(-9) M) to determine
      sensitivity of tissue to feedback regulation. Both stimuli act at the
      hypothalamic level and indirectly modulate GH release via effects on hypothalamic
      factors. Results of this study indicate that tissue from control male rats is
      responsive to the clonidine-induced GH surge by 10 days of age and to feedback
      depression of GH release by 20 days of age. This sensitivity persists after
      puberty and is associated with corresponding changes in somatotropin-release
      inhibiting factor (SRIF) and GH-releasing factor (GRF) release (i.e., clonidine
      inhibits SRIF and stimulates GRF release, and human GH reverses this pattern).
      Fetal ETOH exposure depresses GH sensitivity to both stimuli in male pups (age x
      diet x drug: p < 0.002), and this depressed sensitivity is expressed by 30 days
      of age by reduced responses to alpha 2-adrenergic stimulation and GH feedback
      (drug x diet: p < 0.002 and p < 0.001 for 30 and 50 days of age, respectively).
      This effect of ETOH on GH release was associated with feedback insensitivity of
      SRIF (drug x diet: p < 0.003, at 50 days of age) and GRF [drug x diet; p < 0.044
      at 30 days; clonidine vs. clonidine and GH: p > 0.05 (NS) at 50 days of age for
      ETOH pups]. The depressed response of GH to clonidine after puberty may be
      attributable to a combination of the trends toward decreased sensitivity of both
      SRIF and GRF at this age. The female GH axis was both less sensitive to stimuli
      and less effected by ETOH than corresponding tissue from male rats (sex x age x
      drug x diet: p < 0.011). GH release from control female pituitaries was sensitive
      to clonidine before, but not after, puberty and insensitive to GH feedback at
      both developmental stages. On the other hand, there was a specific effect of ETOH
      on SRIF release at 10 days of age (diet x drug: p < 0.014), and SRIF release
      remained sensitive to clonidine in pups from all diet groups after puberty.
      Because GH release was not influenced by these changes in SRIF, these findings
      suggest that GH release is less sensitive to SRIF in females. In conclusion, this
      study suggests that fetal ETOH exposure interferes with the development of the
      sensitivity of the GH axis to alpha 2-adrenergic stimulation and feedback in
      males. Thus, the male GH axis is both more sensitive to the stimuli tested in
      this study and more effected by ETOH than the female axis. Furthermore, the
      effects of ETOH on these mechanisms do not alter GH release in males until the
      peripubertal period. It is likely, therefore, that the GH regulatory mechanism
      examined in this study does not contribute to growth retardation before puberty.
      If the effects of ETOH on GH release contributes to growth retardation in
      prepubertal males and in females, it most likely involves other regulatory
      mechanisms. On the other hand, because the adult pattern of GH release is
      programmed during development, the influence of ETOH on these developmental
      events may influence the male pattern of GH release and GH activity in adulthood.

PMID- 9267533
TI  - Behavioral similarities and differences among alcohol-preferring and 
      nonpreferring rats: confirmation by factor analysis and extension to additional
      groups.
AB  - Thirteen behavioral variables from six tasks were measured in alcohol-preferring
      (AA, FH, and P) and -nonpreferring (ANA, FRL, and NP) rat lines/strains and
      subjected to Factor Analysis. Four Independent factors accounted for > 90% of the
      variance. Defecation in the open field and ultrasonic vocalizations after an air
      puff were negatively correlated with alcohol intake and preference, whereas the
      increase in daily fluid intake in the presence of saccharin was positively
      correlated. Other factors could be labeled Activity, Emotionality, and immobility
      Factors, and each was independent of the Alcohol Factor. When an additional
      alcohol-preferring rat line (HAD) and two additional nonpreferring groups (LAD
      and ACI) were tested, they were found to differ on most behaviors that were
      associated with alcohol intake and preference in the Factor Analysis;
      vocalizations and saccharin-induced increase in fluid intake, but not defection.
      A new Factor Analysis was then performed incorporating these three new groups and
      including five new behavioral measures. The following measures had high loadings
      on the Alcohol Factor: alcohol intake under choice conditions; alcohol
      preference; forced alcohol intake; alcohol acceptance (forced alcohol
      intake/basal water intake x 100); ultrasonic vocalization; saccharin intake;
      saccharin-induced increase in daily fluid intake; defecation in the open field
      test; and immobility in a modified forced swim test. These findings indicate that
      there are indeed certain behavioral characteristics that are common among alcohol
      preferring rat lines/strains, but there are also substantial group differences on
      other behavioral measures. For those behavioral measures reflecting emotionality
      (defecation and ultrasonic vocalization) that loaded highly on the Alcohol
      Factor, the alcohol-preferring rats had lower scores.

PMID- 9267535
TI  - Deposition of cellular fibronectin increases before stellate cell activation in
      rat liver during ethanol feeding.
AB  - Cellular fibronectin (cFN)-a structural extracellular matrix protein-facilitates
      cell adhesion, migration, and differentiation during organ development; wound
      healing; tissue regeneration; and fibrogenic processes. cFN is deposited early in
      various fibrotic diseases and seems to function as a template for deposition of
      other extracellular matrix proteins, such as collagen type I and laminin, in the
      injured area. We have compared the relative changes in cFN levels with other
      pathogenic markers of alcoholic liver injury over time of ethanol feeding in the
      rat. Male Wistar rats were allowed free access to a liquid diet containing 36% of
      total energy as ethanol or pair-fed an isocaloric control diet for 4, 8, and 12
      weeks. Serum alanine aminotransferase activity and total liver lipid were
      increased in ethanol-fed animals, compared with pair-fed controls after 4, 8, and
      12 weeks of feeding. Liver lipid content was higher in ethanol-fed rats as early
      as 4 weeks and was further increased by 12 weeks of feeding. Total fibronectin
      and cFN protein quantity was greater in liver from ethanol-fed rats after 8 and
      12 weeks (fibronectin: 2.3-fold and 2.6-fold; cFN: 4.3-fold and 2.6-fold higher
      than pair-fed at 8 and 12 weeks, respectively). alpha-Smooth muscle actin, an
      indicator of hepatic stellate cell activation, was increased in the liver of
      ethanol-fed rats after 12 weeks of feeding (344% higher compared with pair-fed),
      with no differences observed at any earlier time points. In summary, increases in
      hepatic immunoreactive cFN content were observed subsequent to increased liver
      lipid concentration, but before hepatic stellate cell activation in rats fed the
      ethanol-based diet. These data suggest that deposition of cFN in the liver during
      long-term ethanol consumption may represent an early response to injury similar
      to that observed in other models of liver injury and wound healing.

PMID- 9267534
TI  - Effects of prenatal ethanol exposure on parvalbumin-expressing GABAergic neurons
      in the adult rat medial septum.
AB  - Exposure of human fetuses to ethanol often results in the fetal alcohol syndrome.
      Animal models of fetal alcohol syndrome have been developed and used to examine
      the consequences of prenatal ethanol exposure on the central nervous system. The
      objective of this study was to determine the long-term effects of prenatal
      ethanol exposure on parvalbumin-expressing (PA+) GABAergic neurons of the rat
      medial septum. Pregnant Long-Evans rats were maintained on 1 of 3 diets from
      gestational day 0 to 21: an ethanol-containing liquid diet in which ethanol
      accounted for 35% of the total calories, a similar diet with the isocaloric
      substitution of sucrose for ethanol, or a lab chow control diet. Offspring were
      killed on postnatal day 60, and their brains were prepared for parvalbumin
      immunocytochemistry. Female rats exposed to the ethanol-containing diet during
      gestation had 42% fewer PA+ neurons in the medial septum and reduced PA+ cell
      density when compared with female rats exposed to the sucrose diet. Ethanol
      females also had fewer PA+ neurons per unit volume than sucrose females. Male
      rats exposed to ethanol did not display a similar reduction in PA+ neurons or
      density. No effect of prenatal diet was found on the area or volume of the medial
      septum, nor were cell diameters affected. As such, prenatal exposure to ethanol
      seems to reduce permanently the number of PA+ neurons in the female rat medical
      septum without affecting area, volume, or neuronal size. Functional implications
      and possible relations to the fetal alcohol syndrome are discussed.

PMID- 9267536
TI  - Time course of acamprosate action on operant ethanol self-administration after
      ethanol deprivation.
AB  - The effects of the new alcohol anticraving compound acamprosate on the alcohol
      deprivation effect were tested in an operant two-lever free choice paradigm with
      concurrent water. Two groups of rats were tested after long-term voluntary
      ethanol self-administration: the "continuous access" group consisting of animals
      that had continuous access to ethanol before operant testing; and the "limited
      access" group that was tested only after ethanol deprivation. The limited access
      group exhibited a strong alcohol deprivation effect with immediate high ethanol
      consumption and preference. Acamprosate (100, 200, or 400 mg/kg) dose-dependently
      reduced lever pressing for ethanol and, accordingly, ethanol consumption in both
      groups in a 23-hr session. The consumption-reducing effect was still evident at
      the end of the session. Ethanol preference was dose-dependently reduced during
      the first hour of the session, but returned to basal levels before the end of the
      23-hr session in both groups. Thus, the time course of preference reduction was
      not identical with that of the reduction of ethanol consumption. Surprisingly,
      preference reduction was observed only after a considerable amount of ethanol had
      been consumed. These results suggest that the specific effect of preference
      reduction depended on the simultaneous presence of sufficient levels of
      acamprosate and ethanol, and that the longer-lasting reduction of ethanol
      consumption was the consequence of this experience.

PMID- 9267537
TI  - Chronic alcohol consumption causes accelerated myocardial preconditioning to
      ischemia-reperfusion injury.
AB  - We have previously demonstrated that chronic alcohol consumption (8 to 10 weeks
      with ethanol as 36% of the caloric intake) does not exacerbate the effects of
      ischemia reperfusion injury on the heart. In those same studies, however, Gram
      negative sepsis caused myocardial depression in both control and alcoholic rats,
      but also protected hearts from further damage due to ischemia-reperfusion. In the
      present study, we determined if preconditioning, a very short ischemia
      reperfusion episode that protects the heart from more prolonged ischemia, would
      have similar effects on hearts from alcoholic and control rats with or without
      sepsis. Thus, rats were fed a liquid diet supplemented with ethanol or dextrin
      for 8 to 10 weeks. Some alcoholic and control rats were made septic with
      Escherichia coli injected into the subcutaneous space, whereas others received an
      injection of sterile saline. Isolated, isovolumically beating hearts were studied
      the following day. Hearts were made ischemic for 5 min, reperfused for 5 min, and
      then made ischemic for 35 min and reperfused for 25 min. Data from similar groups
      of hearts receiving only 35 min ischemia, and studied at the same time as the
      present groups, have been previously reported. The 5-min preconditioning episode
      was more effective in protecting hearts in the alcohol group than in the control
      group. Postischemic left ventricular developed pressure and +dP/dtmax were not
      significantly decreased from the preischemic values in the alcohol group, but
      were significantly decreased in the control group. The time to recovery of
      spontaneous contractions was decreased by preconditioning in the alcohol group
      but not in the control group, and the recovery of coronary flow was enhanced in
      the alcohol group, but not in the control group by pre-conditioning. Thus a
      single 5-min ischemic procedure was effective in protecting the heart from
      prolonged ischemia in the alcohol group, whereas it was not sufficient to elicit
      protection in the control group. Sepsis depressed preischemic function in both
      groups, but recovery from ischemia was complete.

PMID- 9267538
TI  - Effects of prenatal and early postnatal ethanol exposure on [3H]MK-801 binding in
      rat cortex and hippocampus.
AB  - The effects of prenatal and/or early postnatal exposure to ethanol at high
      concentrations on N-methyl-D-aspartate (NMDA) receptor number and functioning in
      the weanling rat were examined. The binge-like exposure protocol was used in an
      animal model of acute ethanol effects at two critical periods of development.
      [3H]MK-801 binding parameters for the internal channel phencyclidine site were
      assessed in the presence of 10 microM glutamate and 10 microM glycine activation.
      Four treatment groups were included: (1) animals exposed to ethanol both prenatal
      and postnatal; (2) animals exposed only prenatal; (3) animals exposed early
      postnatal only; and (4) control animals with no exposure to ethanol. The results
      of the [3H]MK-801 binding experiments showed that both prenatal and postnatal
      exposure to ethanol resulted in a significant decrease in the density of NMDA
      receptors. In addition, data indicated an apparent increase in the percentage of
      high-affinity state (open channel state) relative to low-affinity state (close
      channel state) receptors in the ethanol-treated groups. These results show that
      both prenatal and postnatal ethanol exposure decrease NMDA receptor density in
      the cortex and hippocampus. The findings are consistent with previous
      observations by our laboratory and others that NMDA-mediated calcium influx is
      reduced in these regions, as well as in whole brain by prenatal ethanol exposure.
      It is suggested that after ethanol exposure, the remaining functional NMDA
      receptors might have altered sensitivity to coagonist activation with an
      increased probability of channel opening.

PMID- 9267539
TI  - Ethanol reduces expression of the nerve growth factor receptor, but not nerve
      growth factor protein levels in the neonatal rat cerebellum.
AB  - The cerebellum is especially vulnerable to ethanol's neurotoxic effects during
      development, and ethanol exposure during the brain growth spurt will deplete
      cerebellar neurons. The mechanisms undertying this neuronal cell loss remain
      elusive. Nerve growth factor (NGF) is a neurotrophin that promotes cell survival
      in various brain areas, and there is evidence that NGF may play a role in the
      developing cerebellum. This study examined whether ethanol exposure of the
      neonatal rat cerebellum altered the levels of either NGF or the expression of p75
      and trkA, which are two components of the NGF receptor. Ethanol exposure had no
      effect on NGF levels in the neonatal cerebellum, as determined by an NGF-specific
      ELISA. Immunohistochemical labeling techniques indicated that both the p75 and
      trkA NGF receptors were expressed on Purkinje cell dendrites in the developing
      cerebellum, with posterior lobules expressing higher levels of p75 and trkA NGF
      receptor, compared with anterior lobules. Ethanol exposure of neonatal rats
      reduced the expression of both p75 and trkA NGF receptors on the Purkinje cell
      dendrites. These results suggest that ethanol could interfere with neurotrophic
      support of Purkinje cells by reducing the levels of available NGF receptor.

PMID- 9267540
TI  - Development of a screening questionnaire for the general hospital and general
      practices.
AB  - The purpose of this study was to develop a sensitive as well as brief screening
      questionnaire by combining the well-known instruments CAGE and the Michigan
      Alcoholism Screening Test (MAST) in detecting patients with alcohol dependence or
      abuse in general hospitals and general practices. The number of items was reduced
      by means of logistic regression and item analysis based on data of 1,167
      consecutive admissions of a general hospital who completed both questionnaires.
      Further data were derived from a sample of 774 patients from 10 randomly selected
      general practices. A solution with nine items was validated in a second sample of
      436 hospital inpatients. In all three samples, cases screening positive were
      interviewed using the Schedules for Clinical Assessment in Neuropsychiatry to
      provide ICD-10 and DSM-III-R or DSM-IV diagnosis. In addition, 103 subjects with
      negative screening results were interviewed in the second general hospital
      sample. On grounds of the data of all three samples, a solution of seven items
      was chosen. This instrument comprises two CAGE and five MAST questions (Leubeck
      Alcohol Dependence and Abuse Screening Test; LAST) and was significantly higher
      in sensitivity than CAGE and SMAST. Data were robust in all three samples. It is
      concluded that the LAST is an optimized instrument for use in general hospital
      and general practice.

PMID- 9267541
TI  - Alcohol use disorders, consumption patterns, and health-related quality of life
      of primary care patients.
AB  - This study examined the association of alcohol use disorders and consumption
      patterns with various dimensions of Health-Related Quality of Life (HRQOL) in
      primary care patients, as measured by the SF-36 Health Survey. A probability
      sample of 1333 primary care patients completed the Alcohol Use Disorder and
      Associated Disabilities Interview Schedule to determine the presence of alcohol
      abuse or dependence disorders, and answered questions about patterns of alcohol
      consumption. Physical and Mental Health Component Summaries and primary scales of
      the SF-36 were used as measures of HRQOL. Patients meeting criteria for alcohol
      dependence scored lower (poorer HRQOL) on the Mental Health Component Summary and
      each primary scale of the SF-36, whereas no differences were observed for alcohol
      abusers compared with patients not meeting criteria for a disorder. The
      association of alcohol dependence with diminished mental health functioning was
      mediated by its co-occurrence with mood and anxiety disorders. Patients who drank
      in a Frequent, Low-Quantity pattern generally had better overall HRQOL than
      patients from other consumption groups. Binge drinkers and Frequent, High
      Quantity Drinkers showed markedly lower scores in the areas of Role Functioning
      and Mental Health. In contrast to recent studies of mental health problems in
      primary care, alcohol use disorders and consumption patterns seem to have a
      modest impact on patients' HRQOL. These effects, though, vary by dimension of
      functioning, the presence of alcohol dependence rather than abuse, and pattern of
      alcohol consumption. Global measures of HRQOL such as the SF-36 Health Survey may
      provide important indicators of treatment effectiveness in primary care
      intervention studies for patients with drinking problems.

PMID- 9267542
TI  - Naltrexone biotransformation and incidence of subjective side effects: a
      preliminary study.
AB  - When administered orally, naltrexone undergoes extensive biotransformation and is
      metabolized to 6 beta-naltrexol and other minor metabolites. Naltrexone has been
      recently approved by the Food and Drug Administration for the treatment of
      alcohol dependence. An important clinical issue with naltrexone treatment is
      predicting patient compliance, which may be influenced by adverse side effects
      experienced during the medication. We investigated whether subjective side
      effects were related to urinary concentrations of naltrexone and its metabolite 6
      beta-naltrexol 3 hr after administration of 50 mg po naltrexone in 24 male
      moderate-to-heavy social drinkers. The results showed significantly higher levels
      of urinary 6 beta-naltrexol (p < 0.05) in those subjects who experienced one or
      more side effect (i.e., headache, nausea, anxiety, or erection). Urinary
      naltrexone levels did not differ between the groups. Results also showed an
      approximate 10:1 ratio of 6 beta-naltrexol to naltrexone levels and a significant
      positive correlation between the parent compound and metabolite, suggesting
      parallel renal clearance. The results of this study suggest a possible mechanism
      for the side effects observed after acute administration of naltrexone.

PMID- 9267543
TI  - Smooth pursuit eye movement dysfunction in abstinent cocaine abusers: effects of
      a paternal history of alcoholism.
AB  - The present study evaluated smooth pursuit eye movement (SPEM) function in 36
      cocaine-dependent patients, with or without a paternal history of alcoholism, and
      12 nondrug-dependent normal volunteers. None of the subjects in either group met
      DSM-III-R diagnostic criteria for schizophrenia, or delusional, major affective,
      or schizotypal personality disorders. None possessed a history of seizures,
      significant head injury, HIV-1 infection, or regular medication use. SPEMs were
      elicited by a pendulum, oscillated at 0.5 Hz, and recorded using electro
      oculographic techniques. Tracking accuracy was estimated by the power of the
      horizontal electro-oculograph at the stimulus oscillation frequency. Analyses
      revealed that the SPEM tracking accuracy of cocaine-dependent patients without a
      paternal history of alcoholism was superior to that of the normal control group.
      SPEM tracking in these patients correlated positively with years of cocaine and
      polysubstance abuse. In contrast, patients with a paternal history of alcoholism
      exhibited subnormal SPEM tracking performance. These differences could not be
      explained by other family history, demographic, or drug use variables.

PMID- 9267544
TI  - Changes in alcohol use and alcohol-related problems among 7th to 12th grade
      students in New York State, 1983-1994.
AB  - Three comparable representative samples of 7th to 12th grade students in New York
      State were surveyed in 1983, 1990, and 1994 to determine changes in the patterns
      of alcohol use over the past decade. Each of the three samples was large (n =
      27,335, 23,860, and 19,321, respectively), permitting detailed analysis of
      changes in alcohol use in various adolescent subgroups according to age, gender,
      and race/ethnicity. Previous research revealed that there were marked decreases
      in the prevalence of overall drinking, heavy drinking, and alcohol-related
      problems from 1983 to 1990, yet recent national reports indicate that since 1990
      there has been an upsurge in substance use among adolescents. Whereas the
      proportion of drinkers did not significantly increase between 1990 and 1994,
      average consumption, heavy drinking, and alcohol-related problems all showed
      modest, but significant increases in the 1990s. Furthermore, between 1990 and
      1994, the age distributions for alcohol use, heavy drinking, and alcohol problems
      changed, as evidenced by significant age by year of survey interactions. These
      findings indicate that adolescents are currently drinking, drinking heavily, and
      experiencing alcohol-related problems at younger ages that they were in past
      years. Prevention efforts should be targeted at delaying alcohol use in early
      adolescence.

PMID- 9267545
TI  - Carbohydrate-deficient transferrin as a marker of alcohol consumption in male
      patients with liver disease.
AB  - Carbohydrate-deficient transferrin (CDT) has been proposed as a marker of alcohol
      abuse. However, its value in patients with associated liver disease is still
      controversial. The aim of the study was to investigate the usefulness of CDT as a
      marker of alcohol consumption in patients with liver disease. We measured serum
      levels of CDT and those of commonly used hematological and biochemical markers,
      mean corpuscular volume (MCV), transaminases (AST and ALT), and gamma
      glutamyltransferase in 179 male subjects divided into four groups: 45 active
      drinkers (13 with normal liver, 21 with fibrosteatosis, and 11 with liver
      cirrhosis), 45 abstinent chronic alcoholics (18 with and 27 without liver
      disease), 58 patients with nonalcoholic liver disease, and 31 healthy controls.
      Serum CDT in active alcoholics was 37.5 +/- 3.6 units/liter, being significantly
      higher than that of abstinent alcoholics (20.3 +/- 1.5 units/liter), patients
      with nonalcoholic liver disease (18.1 +/- 1.1 units/liter), and controls (13.1 +/
      0.8 units/liter). Contrary to the other markers, no significant differences were
      observed in CDT values in relation with the presence and severity of liver
      disease in either the active drinkers or in the abstinent alcoholics. The
      sensitivity and specificity of CDT as a marker of alcoholism in the series as a
      whole was 64% and 82%, respectively, similar to the best conventional marker, MCV
      (64 and 82%). In patients with liver disease, CDT maintained good sensitivity
      (72%) and specificity (83%). Receiver operating characteristic analysis confirmed
      that CDT had a similar diagnostic value to that of MCV, but better than gamma
      glutamyl-transferase and transaminases for the detection of alcohol abusers. The
      good diagnostic efficacy of CDT remained unchanged when analyzing only patients
      with liver disease. We conclude that serum CDT is a good marker of alcoholism and
      is less influenced than the currently used biochemical markers for associated
      liver disease. Thus, CDT is an effective laboratory test to detect alcohol abuse
      regardless of the presence of alcoholic liver disease.

PMID- 9267546
TI  - Gender and alcohol dosing: a procedure for producing comparable breath alcohol
      curves for men and women.
AB  - Gender differences in peak breath alcohol concentrations (BrACs) reached in
      alcohol administration studies can make the interpretation of study findings
      difficult. This study evaluated the CBAC computer program as a way of minimizing
      gender differences in the BrAC curve. After consuming a predrink meal that was
      adjusted by body mass, 31 female and 27 male subjects consumed an alcoholic
      beverage targeted for either 0.04% or 0.08%. Mean peak BrACs for women and men
      were not significantly different. Similarly, the four BrAC readings obtained over
      the first 2 hr postdrink showed no gender differences. A dose x gender
      interaction was observed on time to peak BrAC, with women reaching peak BrAC
      faster than men only in the high dose groups. By decreasing gender differences in
      BrAC curves, this dosing procedure can aid in reducing the potential confound of
      dose and gender.

PMID- 9267547
TI  - Cost and usage impacts of treatment initiation: a comparison of alcoholism and
      drug abuse treatments.
AB  - An extensive literature on substance abuse and mental health treatments suggests
      that they often lead to decreased usage and/or spending on other medical
      treatments. We compare alcohol and drug abuse treatment costs with a model that
      decomposes total treatment costs into amount of treatment (outpatient visits or
      inpatient days) and costs per treatment. The analysis compares alcohol and drug
      abuse treatment costs regarding: (1) the incremental costs attributable to
      changed short-term substance abuse and nonsubstance abuse treatments; (2) the
      impacts of current substance abuse treatments on short-term nonsubstance abuse,
      long-term substance abuse, and long-term nonsubstance abuse treatments; and (3)
      the difference in inpatient and outpatient impacts. Our findings indicate that
      alcoholism and drug abuse treatment initiation have similar impacts on coincident
      and subsequent utilization and costs. For both treatments, the largest portions
      of the cost impacts occur for inpatient treatments, and for treatments that occur
      within 6 months of the initiation. The similarity of results suggests that it may
      often be reasonable to infer utilization and cost impacts for one type of care
      from studies that examine the other.

PMID- 9267548
TI  - Endogenous production of methanol after the consumption of fruit.
AB  - After the consumption of fruit, the concentration of methanol in the human body
      increases by as much as an order of magnitude. This is due to the degradation of
      natural pectin (which is esterified with methyl alcohol) in the human colon. In
      vivo tests performed by means of proton-transfer-reaction mass spectrometry show
      that consumed pectin in either a pure form (10 to 15 g) or a natural form (in 1
      kg of apples) induces a significant increase of methanol in the breath (and by
      inference in the blood) of humans. The amount generated from pectin (0.4 to 1.4
      g) is approximately equivalent to the total daily endogenous production (measured
      to be 0.3 to 0.6 g/day) or that obtained from 0.3 liters of 80-proof brandy
      (calculated to be 0.5 g). This dietary pectin may contribute to the development
      of nonalcoholic cirrhosis of the liver.

PMID- 9267549
TI  - Adolescent risk factors and the prediction of persistent alcohol and drug use
      into adulthood.
AB  - Adolescence is a time of heightened risk for relatively intensive alcohol and
      other drug use behaviors. However, heavy use is often "adolescence-limited,"
      giving way to moderation or cessation in adulthood. We examined individual
      differences in risk factors at age 18 that were predictive of alternative alcohol
      and drug use trajectories from adolescence to adulthood. Data were collected
      prospectively on four occasions from participants in the Rutgers Health and Human
      Development Project. Subsets of individuals representing three prototypical
      trajectories of (1) consistently low alcohol and drug use during adolescence and
      early adulthood; (2) heavier alcohol or drug use during adolescence, but not
      during adulthood; and (3) persistent heavier alcohol or drug use from adolescence
      into adulthood were found to differ significantly on a number of intrapersonal,
      behavioral, and environmental risk factors, with the adolescence-limited group
      consistently scoring between the other two groups. Based on these results, a
      composite risk index was constructed. In the total sample, however, when the
      effect of alcohol and drug use behaviors at age 18 was controlled, the composite
      risk index was unrelated to adult (age 28 to 31) levels of alcohol and drug use
      and consequences. Thus, in this community sample, well-documented risk factors
      assessed in adolescence did not exhibit any direct, longterm effects on use
      intensity and problems in adulthood. It is concluded that the assessed risk
      factors (disinhibition, cognitive structure, play, deviant coping, friends'
      deviance, and stressful life events) are not immutable, but subject to individual
      and normative changes during the transition from adolescence to adulthood. More
      research is needed to determine the long-term stability of risk factors, and how
      changes in risk factors over time, discontinuities in what constitutes risk in
      adolescence versus adulthood, and proximal adult protective factors that
      compensate for early risk contribute to developmental patterns of use.

PMID- 9267550
TI  - Voices of the afflicted.
AB  - Over the past 10 years, I have been privileged to conduct education forums for
      audience containing many recovering alcoholics or otherwise chemically dependent
      persons. In these forums about the addictive diseases and their treatment and
      research possibilities, significant interaction with the audience members occurs.
      During these interactions, certain anecdotal phenomena seem to predominate. The
      repetitive nature of these reports suggests the need for systematic
      investigation. As with editorial comments in major medical journals, observed
      phenomena and unanswered questions from those afflicted can be valuable in the
      generation of testable hypotheses. Perhaps the ideas presented herein will be
      useful in the development of future research on alcohol abuse and alcohol
      dependence.

PMID- 9267551
TI  - Clinical use of leeches in reconstructive surgery.
AB  - Although medicinal bloodletting with leeches is a practice that dates back 3500
      years, leeches have been used in reconstructive surgery for only the past 35
      years. In this article, the indications, mechanisms of action, and guidelines for
      using leeches in reconstructive surgery are reviewed.

PMID- 9267552
TI  - A review of Morquio syndrome.
AB  - Morquio syndrome is one of the mucopolysaccharidoses. Glycosaminoglycans
      accumulate within the cells, leading to many systemic alterations. Alterations in
      connective tissue and cartilage ground substance result in abnormal formation and
      growth of the skeletal system. The major orthopedic manifestations include
      shortening of the trunk and limbs, spinal curvature, odontoid hypoplasia with
      upper cervical instability, and lower-limb alignment problems. The management of
      the orthopedic manifestations of this syndrome requires a broader knowledge of
      the genetic, metabolic, and systemic effects of the metabolic alterations.

PMID- 9267553
TI  - Femoral sulcus angle measurements.
AB  - We sought to determine whether the femoral sulcus angle measurement is consistent
      on different radiographic projections of the knee. Seventy-four cadaveric knees
      were radiographed using Merchant, Laurin, and Hughston projections. The
      measurements of the sulcus angle (mean, 138.6 degrees; SD, 6.9 degrees; and
      range, 120 degrees to 155 degrees) obtained with the Merchant technique were
      similar (P = 0.0007) to those obtained with the Hughston (mean, 137.4 degrees;
      SD, 7.6 degrees; range, 122 degrees to 155 degrees) and Laurin (mean, 141.6
      degrees; SD, 6.9 degrees; and range, 125 degrees to 162 degrees) projections.
      Therefore, we submit that either the Hughston or Laurin view can be used instead
      of the Merchant view to reliably measure the femoral sulcus angle.

PMID- 9267554
TI  - Dorsal capsulodesis using suture anchors.
AB  - Scapholunate instability can be treated by stabilizing the scaphoid with the
      dorsal wrist capsule, which acts as a tether to control palmar rotation. We began
      using suture anchors instead of pull-out wires to secure the dorsal capsule to
      the scaphoid. Thirty-eight patients were treated with this method, and 35 were
      followed an average of 24 months. Sixteen were pain free, 12 had pain with
      activity, and 7 required additional surgical treatment. Patients regained 85% of
      expected grip strength, with 25 of the 35 returning to their preinjury job. The
      scapholunate gap, reduced at the time of surgery, recurred in 31 of the 35
      patients, but this alone did not correlate with symptoms. This procedure improves
      symptoms in a majority of patients, but like other procedures described for
      scapholunate instability, it does not completely cure the problem.

PMID- 9267555
TI  - Pyrexia after total knee replacement. A cause for concern?
AB  - Ninety patients who had undergone 92 total knee replacements were reviewed to
      determine predictors of postoperative pyrexia and to evaluate the relative value
      of septic screening in this group of patients. Postoperative pyrexia was defined
      as an axillary temperature greater than 37 degrees C (98.4 degrees F) on any or
      all of the 5 days after surgery. All of the patients in this series developed a
      postoperative pyrexia after knee arthroplasty. None of 16 patients (17% of
      arthroplasties) with a temperature of 39 degrees C (102 degrees F) or greater had
      evidence of infection. None of the 4 patients with urinary tract infections
      developed a pyrexia exceeding 38 degrees C (101 degrees F). At a minimum of 2
      years' follow-up, none of the 90 patients had developed an infected arthroplasty.
      Logistic regression analysis showed that the risk of becoming significantly
      febrile (temperature > 39 degrees C) doubled for every unit drop in hematocrit
      and increased fourfold for each unit of blood transfused after surgery.
      Perioperative blood loss and pyrexia were correlated, but the correlation was not
      statistically significant. The duration of procedure, tourniquet time, and
      patient age or sex were not associated with risk of pyrexia. In this series,
      there was no association between a pyrexia greater than 37 degrees C, septic
      screening, and the presence of an infective focus. Early postoperative pyrexia
      after arthroplasty is a normal physiological response, and a significant pyrexia
      can be predicted by a drop in hematocrit and/or after postoperative transfusion.
      Pyrexia in the early postoperative period following total knee arthroplasty
      warrants detailed laboratory and radiographic investigation only in the presence
      of positive physical findings.

PMID- 9267556
TI  - Primary synovial osteochondromatosis of the hip: report of two cases with long
      term follow-up after synovectomy and a review of the literature.
AB  - Primary synovial osteochondromatosis of the hip joint is rare. Two cases treated
      successfully by open synovectomy of the hip joint and removal of loose bodies,
      with a follow-up of 7 years in one case and 5 years in the other, are described.
      A review of all published case reports in the English language suggests that an
      open synovectomy of the hip will relieve pain and may prevent or delay the
      progression of degenerative changes.

PMID- 9267557
TI  - Intraneural mucous cysts of peripheral nerves.
AB  - We present three cases of a rare mucous cyst inside the peripheral nerves of the
      upper extremity; a lateral cutaneous nerve of the forearm, a dorsal sensory
      branch of the ulnar nerve, and a median nerve at the wrist. All our cases were
      intraneural, and we excised longitudinal strips of the cyst wall between nerve
      fascicles in all, preserving nerve function in each case.

PMID- 9267558
TI  - Central perforation of the articular disc of the triangular fibrocartilage
      complex in a 17-year-old girl: could it be congenital?
AB  - A case of a central perforation of the horizontal portion of the triangular
      fibrocartilage complex in a 17-year-old girl is reported. The age of the patient,
      along with normal articular surfaces of the ulnar head and ulnar carpus and the
      lack of an ulnar-positive wrist, made the existence of a degenerative tear
      unlikely. The possibility that the central perforation in this patient could be
      congenital suggests that this defect should be considered in the differential
      diagnosis of ulnar-sided wrist pain in the young patient.

PMID- 9267559
TI  - Coronal fracture of the hamate body.
AB  - A case of a displaced coronal fracture of the hamate body with a 1-month delay in
      diagnosis is presented with a review of the literature regarding hamate-body
      fractures. Mechanism, diagnosis, and treatment options are discussed. This
      diagnosis should be suspected on initial review of plain radiographs, which must
      include an oblique view in any patient presenting with pain after blunt trauma to
      the hand. Open reduction with internal fixation is reserved for unstable,
      displaced fractures. Care should be taken to preserve the vascular supply to the
      displaced fragment, and a two-incision technique is recommended to minimize risk
      to the motor branch of the ulnar nerve.

PMID- 9267560
TI  - Reliable DNA histogram interpretation. Number of nuclei requiring measurement
      with flow cytometry.
AB  - OBJECTIVE: The reasons for conflicting prognostic results as to DNA ploidy and
      cell cycle variables (DNA index, percent S (%S) phase) may be found mainly at
      different levels of the flow cytometric methodology used. The present study
      concentrated on how many nuclei have to be measured with flow cytometry for
      reliable DNA histogram interpretation. STUDY DESIGN: Twenty-three samples of
      fresh frozen and 22 samples of paraffin-embedded material from different sites
      were used. For each sample, 5, 10, 15, 20, 25, 30, 35, 40, 45 and 50 (x1,000)
      events were cumulatively measured. The resulting DNA histograms were analyzed
      with the MultiCycle computer program using a highly reproducible interpretation
      protocol. RESULTS: No disagreements about DNA ploidy classification were found in
      samples with 10,000 or more events for the fresh frozen and 40,000 or more events
      for the paraffin-embedded material. Excluding DNA ploidy disagreements, the DNA
      index was stable in all cases. To obtain a %S-phase cell measurement within 20%
      of the reference value, at least 20,000 and 40,000 events were needed for,
      respectively, DNA diploid and DNA nondiploid cases for the fresh frozen material
      and, respectively, 40,000 and 50,000 events for the paraffin-embedded material.
      CONCLUSION: For reliable combined determination of DNA ploidy, DNA index and %S
      phase cells, at least 40,000 and 50,000 events are necessary for fresh frozen and
      paraffin-embedded material, respectively.

PMID- 9267561
TI  - Nuclear image analysis of p53-positive and -negative cells in breast carcinoma.
AB  - OBJECTIVE: To detect differences in nuclear morphology in breast carcinoma cells
      with different p53 expression. STUDY DESIGN: Immunohistochemical reactions were
      performed on paraffin sections from 88 breast cancers with the monoclonal
      antibody DO-1. By means of an image cytometry workstation, 500 nuclei were
      localized and categorized in an immunohistochemical staining scoring system in
      each case. After destaining and Feulgen staining, the nuclei were relocated and
      measured by means of the workstation. RESULTS: P53-positive nuclei showed greater
      irregularity of the chromatin pattern and stronger granularity of the chromatin.
      There were also differences in the chromatin texture and nuclear shape between
      tumors different in their p53 expression. The p53-negative nuclear population
      from the p53-positive tumors and the whole nuclear population of the p53-negative
      tumors were morphologically different, also. CONCLUSION: Nuclear image analysis
      of immunohistochemically characterized cells allows further insight into the
      relationship of structure and function in malignant tumor cells.

PMID- 9267562
TI  - DNA measurement on histologic slides. Does it work on human tissue?
AB  - OBJECTIVE: To determine the performance of different mathematical methods of
      correcting histograms obtained by densitometric DNA measurement on thin tissue
      sections for cutting artifacts in different types of human tissue. STUDY DESIGN:
      The study group consisted of four different euploid-polyploidizing, nonmalignant
      human tissues (liver, breast cyst with apocrine metaplasia, adenoma of the
      thyroid, condyloma). The section thickness was accurately measured. The
      algorithms of Bins, McCready, Bacus and Haroske were applied to the histograms
      obtained from DNA measurements. The results were compared to those of the
      corresponding single-cell preparations. RESULTS: Correct ploidy equivalents were
      calculated using the algorithm of Bins in very thin sections (+/- 3 microns).
      This was also the case applying the formulas of McCready and Haroske to medium
      thick sections (5.3-5.9 microns). The algorithm of Bacus did not lead to reliable
      results. Measurements on sections thicker than approximately 7 microns led to
      good results without mathematical correction. CONCLUSION: Reliable results can be
      obtained only when knowing the exact section thickness. In very thin sections the
      method of Bins leads to reliable results; in medium-thick sections the methods of
      McCready and Haraske result in correct ploidy values. Sections thicker than 7
      microns do not need histogram correction.

PMID- 9267563
TI  - Histologic and morphometric grading of gliomas. A comparative survival analysis.
AB  - OBJECTIVE: A grading system based upon morphometrically assessed quantitative
      parameters (HOM system) was correlated with the results of classical histologic
      grading (St. Anne/Mayo system [SAMS], 1988, and World Health Organization
      classification, 1993). Validation was done by comparison with survival data.
      STUDY DESIGN: This retrospective study consisted of representative paraffin
      embedded tissue sections of 139 adults who had been surgically treated for
      supratentorial common gliomas between 1988 and 1994. Histologic grading diagnoses
      were adapted to the latest standard. Computer-assisted image analysis of Ki-67
      (MIB1)/ Feulgen-stained sections provided nuclear parameters appropriate to
      define homogeneous grades of malignancy by multivariate statistical analyses:
      average segment length of the minimum spanning trees (ASLMST) for the
      quantitation of tumor growth pattern; nuclear area percentage (NAP), reflecting
      cellularity; and volume-weighted mean nuclear volumes (vV) for estimating nuclear
      size and pleomorphism. RESULTS: Analysis of survival data yielded no
      statistically significant differences between astrocytomas and oligoastroacytomas
      (Lee-Desu test, alpha = 5%). Furthermore, only two prognostically different
      grades could be established, "low grade" and "high grade" gliomas, with the first
      representing SAMS grades 2 and 3 and the latter SAMS grade 4 (alpha = .1%). The
      same applied to HOM grades (alpha = .1%). Cox regression analysis of survival
      data demonstrated that histologic grading diagnoses and NAP tallied best with
      patients' outcome.

PMID- 9267564
TI  - Morphometric analysis in prognostic evaluation of stage I thick cutaneous
      melanomas.
AB  - OBJECTIVE: To determine if morphometric analysis could be useful in
      distinguishing between good and adverse prognosis in thick melanomas. STUDY
      DESIGN: The study group consisted of 30 cutaneous melanomas (CM) (18 superficial
      spreading, 11 nodular and 1 acral lentiginous) measuring 1.5-14.8 mm in diameter.
      Area, perimeter, roundness and aspect ratio of 200 nuclei (100 in the superficial
      areas and 100 in the lower area) were morphometrically studied. After five years
      of follow-up, 18 patients were alive, and 12 had died of the tumor. The data were
      evaluated with univariate and multivariate (Cox's proportional hazard model)
      analysis. RESULTS: Univariate analysis showed that area and perimeter of
      superficial and deep nuclei were significantly larger in CM patients than in
      controls (10 acquired intradermal nevi). Regarding the prognostic role of the
      variables considered, aspect ratio of the deep nuclei (SD only) was significantly
      associated with prognosis. Otherwise, size factors (area and perimeter) had no
      prognostic value. CONCLUSION: Morphometric evaluation of nuclear shape factors in
      the subset of thick CM represents an additional prognostic tool with statistical
      significance.

PMID- 9267565
TI  - Potential use of image analysis for the evaluation of cellular predicting factors
      for therapeutic response in breast cancers.
AB  - OBJECTIVE: To summarize the current literature on the association between
      biologic prognostic factors and therapeutic implications. STUDY DESIGN: To
      illustrate how these biologic factors are determined and how they can affect
      treatment, three patients' biologic profiles and their implications for the
      patients' choice of therapeutic approaches were analyzed. Immunohistochemical
      techniques combined with image analysis was used to evaluate estrogen receptors,
      progesterone receptors, proliferation index and erbB-2. Visual assessment was
      used to evaluate P glycoprotein (MDR1), EGFR and p53. RESULTS: Data from the
      literature stress the importance of biologic profiles for defining tumor behavior
      and patient management. The examples of patients' biologic factors illustrated
      the possible importance of these factors for helping to design treatment.
      CONCLUSION: Today the data on the association of patient response to chemotherapy
      and molecular markers are only starting to accumulate. A larger database is
      needed for a more precise estimation of response probability in order to help
      physicians decide between treatment options.

PMID- 9267566
TI  - Total number of cancer cell nuclei and mitoses in breast tumors estimated by the
      optical disector.
AB  - OBJECTIVE: The total number of cancer cell nuclei, N(nuc), and of mitoses,
      N(mit), in the primary lesion are potentially important indicators of tumor
      biology. In the present study, such estimates were obtained on breast cancers by
      an unbiased stereologic method. STUDY DESIGN: The total number estimates are the
      product of two variables: (1) the volume of tumor, V(T), estimated by the
      Cavalieri principle, and (2) the densities of cancer cell nuclei and of mitoses
      obtained in small, three-dimensional samples (i.e., optical disectors) of 40
      micron-thick methacrylate sections, which were selected systematically at random
      from the whole specimen. RESULTS: In 93 prospectively collected tumors, N(nuc)
      ranged from 0.06 to 7.9 10(9) (median, 0.6 10(9)), and N(mit) ranged from 0.02 to
      64 10(6) (median, 1.5 10(6)). Both N(nuc) and N(mit) correlated significantly
      with V(T) (r = .77 and .60, respectively); however, the steep slopes of the
      regression lines indicated that densities of nuclei and mitoses increased as a
      function of tumor size. On average, N(mit) and estimates of mitotic frequency
      tended to be larger in lymph node-positive patients as compared with lymph node
      positive patients as compared with lymph node-negative ones (2P < or = .08),
      whereas no such relation was found for nuclear counts (2P > or = .40). By
      counting a median number of 195 nuclei and 28 mitoses per tumor, the average
      coefficients of error of N(nuc) and N(mit) were 17% and 32%, respectively; this
      gave seemingly sufficient precision as compared with the huge interpatient
      variation in estimates, 180% and 490%. Moreover, the intraobserver
      reproducibility of density estimates was excellent (r > or = .88). CONCLUSION:
      The present study showed the feasibility, efficiency and reproducibility of the
      unbiased optical disector principle applied to human breast cancer and provided
      data on new parameters of biologic relevance. The technique seems suitable for
      use in experimental oncology, but further studies are needed to investigate its
      clinical value.

PMID- 9267567
TI  - Image and flow cytometric analyses of DNA content in human solid tumors. A
      comparative study.
AB  - OBJECTIVE: To compare the sensitivity and potentials of flow and image cytometry
      in assessing DNA content. STUDY DESIGN: The study was performed on 152 tumors
      (oral cavity, uterine cervix, bladder, colorectum, breast). Flow cytometry was
      carried out on cell suspensions from frozen samples, and the results were
      expressed as the DNA index. Image cytometry was performed on Feulgen-stained
      sections, and the results were expressed as the rate of cells exceeding 2.5c or
      5c. For colorectal and breast cancers, DNA content by image cytometry was also
      measured on imprints and was expressed as the DNA index or rate of cells
      exceeding 2.5c and 5c. RESULTS: Among flow cytometric diploid tumors, image
      cytometric analysis performed on histologic sections showed about 80% diploid
      tumors from the uterine cervix and breast cancers. The frequency decreased to 36%
      for oral cavity cancers. Generally satisfactory concordance was observed when
      flow cytometric aneuploid tumors were analyzed. A highly significant correlation
      was observed between DNA indices observed by flow and image cytometry on
      imprints. CONCLUSION: Image cytometry appears more sensitive than flow cytometry
      in detecting small, aneuploid clones, but its main limitation is the low power in
      resolving near-diploid cell populations. The results on imprints indicate that
      image cytometry is a potential alternative approach for small tumor samples.

PMID- 9267568
TI  - Diagnostic implications of p53 protein reactivity in nasal mucosa of nickel
      workers.
AB  - OBJECTIVE: To investigate whether the quantitation of p53 protein reactivity in
      nasal biopsies could be related to nickel exposure by comparing nickel workers
      with various control groups. STUDY DESIGN: Nasal biopsies taken from nickel
      workers (n = 93) were compared immunohistochemically to various controls,
      including office staff members (n = 34) and hospital attendants (n = 6). The
      material was studied immunohistochemically with p53 antibody DO-1. p53 Protein
      positive cells were counted at 400x magnification. RESULTS: p53 Protein
      reactivity was found in 54% (49/93) of nickel workers, 50% (17/34) of office
      staff members, 67% (4/6) of hospital attendants. No differences were seen between
      roasting/smelting, electrolysis and other workers in the refinery. The positive
      cells were present predominantly in the basal layer of the epithelium. The number
      of positive nasal cells per field in the hospital attendants on the average was
      half of that in the workers and the office staff in the refinery. In no case in
      the control group were more than 10 cells per field seen. No significant
      differences in p53 protein positivity were observed between the three nickel
      worker groups and between production workers and office staff members.
      CONCLUSION: Accumulation of p53 protein in nickel workers seems not to be
      attributable to nickel exposure. The lack of p53 protein positivity in fetal
      tissues shows that the accumulation of p53 protein is an event taking place after
      birth. Stimuli in the natural environment during life may explain p53 protein
      positivity.

PMID- 9267569
TI  - Densitometric and chromatin texture parameters of hepatocyte nuclei during
      controlled autolysis.
AB  - OBJECTIVE: To determine the extent of the effect of autolytic changes in
      hepatocyte nuclei on the results of measurements of integrated optical density
      (IOD) of nuclei stained by the Feulgen method and its possible relationship with
      changes in chromatin texture. STUDY DESIGN: Cytologic smears obtained from five
      pig livers by means of fine needle biopsy were fixed in 10% formalin at six time
      points after slaughtering (0-18 hours) and stained per Feulgen. In the hepatocyte
      nuclei IOD measurements were performed and supplemented with quantitative texture
      analysis. Texture analysis was carried out with our own algorithm, based on the
      movement of global gravity centers of heterochromatin granules during two-level,
      iteratively changed, grey thresholding. RESULTS: The variability coefficients of
      IOD of diploid hepatocytes during autolysis increased from 0.061 (0 hours) to
      0.363 (18 hours), and the ploidy histograms became aneuploid. The texture of
      chromatin became more homogeneous, but other features of the texture did not
      indicate a significant correlation with the duration of autolysis. CONCLUSION:
      Autolysis is an important factor, which may influence the accuracy of DNA content
      and shape of ploidy diagrams. Changes in the morphologic pattern of
      heterochromatin may play a role in this, but the study was not conclusive because
      only one of six texture parameters (number of granules) changed parallel to mean
      IOD and autolysis time.

PMID- 9267570
TI  - Effect of ultrafast Papanicolaou staining on nuclear and textural features in
      breast cancer cytology.
AB  - OBJECTIVE: To compare quantifiable cytologic features of mammary lesions prepared
      using the Ultrafast Papanicolaou, Diff-Quik and Papanicolaou methods. STUDY
      DESIGN: Thirteen patients with mammary lesions were studied; the majority had
      histopathologic diagnoses of infiltrating ductal carcinoma. For each patient,
      three specimens were prepared, using (1) Diff-Quik staining after air drying, (2)
      Papanicolaou staining after wet fixation, and (3) the Ultrafast Papanicolaou
      procedure. Descriptors of nuclear size, shape and texture were computed from an
      average of 61.9 normalized nuclear images per specimen. Differences between
      preparation methods were analyzed using two-way analysis of variance. RESULTS:
      While differences in nuclear size, shape and texture existed between the three
      cytologic staining methods, only form factor varied significantly between
      conventional and Ultrafast Papanicolaou stain. Nuclear areas were larger in
      Ultrafast Papanicolaou specimens than conventional Papanicolaou specimens, but
      this difference was not statistically significant. CONCLUSION: The Ultrafast
      Papanicolaou procedure improves on conventional Papanicolaou staining in terms of
      speed, with no important quantifiable differences in nuclear morphology.

PMID- 9267571
TI  - Analytical comparison of volume-weighted mean nuclear volume between specimens
      from transrectal biopsy and transurethral resection of the prostate.

PMID- 9267572
TI  - Effect of rapid maxillary expansion on hearing loss.

PMID- 9267573
TI  - Distal molar movement using the pendulum appliance. Part 1: Clinical and
      radiological evaluation.
AB  - Intra-arch distal molar movement techniques have recently assumed an important
      role in clinical orthodontics. In this study, the dental and skeletal effects of
      the pendulum appliance, applying 200 to 250 g of force to the molars in 13
      patients (age range 8 years to 13 years 5 months) were evaluated by means of
      cephalometric radiographs. The results showed that the pendulum appliance moved
      the molars distally without creating dental or skeletal bite opening and with
      little incisor anchorage loss. However, important molar tipping should be taken
      into consideration when using this appliance.

PMID- 9267574
TI  - Distal molar movement using the pendulum appliance. Part 2: The effects of
      maxillary molar root uprighting bends.
AB  - A clinical study was recently undertaken to evaluate the dental and skeletal
      effects of the pendulum appliance (PA). In the present study, the appliance was
      modified by incorporating an uprighting bend into the distalizing spring during
      the second phase of treatment to avoid excessive distal tipping of the maxillary
      molars. The sample consisted of 20 patients: 8 females and 12 males, mean age
      13.11 +/- 1.10 years. Eight of the patients were subjected to a slow rate of
      maxillary expansion. Measurements were obtained from cephalometric headfilms
      prior to (T1) and the day of removal (T2) of the PA. Treatment changes were
      analyzed and compared with the previous study. The PA with uprighting bends led
      to reduced molar tipping without significantly changing the effects of the PA,
      with the exceptions of 0.62 mm more anchorage loss of the maxillary incisor edge
      and increased treatment time. There was no significant difference in anchorage
      loss between the patients with and without maxillary expansion.

PMID- 9267575
TI  - The mechanism of Class II correction during Herbst therapy in relation to the
      vertical jaw base relationship: a cephalometric roentgenographic study.
AB  - This retrospective Herbst study analyzes and compares the sagittal dental and
      skeletal effects contributing to Class II correction in subjects with small or
      large pretreatment mandibular plane angles. Lateral headfilms of 15 hypodivergent
      (ML/NSL < or = 26 degrees) and 16 hyperdivergent (ML/NSL > 39 degrees) Class II
      subjects treated to a Class I occlusal relationship with the Herbst appliance
      were analyzed. Radiographs were taken before and after an average treatment
      period of 7 months. Cephalograms were evaluated according to the method of
      Pancherz. In both groups, impprovements in sagittal incisor and molar
      relationships were achieved by greater dental than skeletal changes. The amount
      of skeletal changes contributing to overjet and molar correction was larger in
      the hyperdivergent group (37% and 44%, respectively) than in the hypodivergent
      group (25% and 25%, respectively). Dental and skeletal changes contributing to
      Class II correction were found to be independent of the vertical jaw base
      relationship. Thus, a hyperdivergent jaw base relationship did not affect the
      treatment response unfavorably.

PMID- 9267576
TI  - Case report: modified use of the Jasper Jumper appliance in a skeletal Class II
      mixed dentition case requiring palatal expansion.
AB  - The Jasper Jumper appliance provides a method of Class II correction with an
      active force component that the patient cannot remove. A modification of classic
      Jasper Jumper usage is illustrated in a mixed dentition case where full banding
      is impractical. This report shows how Jasper Jumper springs can be attached to a
      fixed maxillary expansion appliance and a lower lingual holding arch for
      correction of a Class II malocclusion. Cephalometric analysis revealed that
      despite seemingly adequate anchorage for the springs, treatment changes were
      largely dentoalveolar, with minimal improvement in the underlying skeletal
      structures. Some restraint of maxillary growth was found, but most of the overjet
      correction was due to forward movement of the mandibular dentoalveolar complex
      and retraction of the maxillary dentoalveolar complex.

PMID- 9267578
TI  - Nonsurgical rapid maxillary alveolar expansion in adults: a clinical evaluation.
AB  - Palatal expansion in adults has traditionally been performed on a very limited
      basis. The expansion has been thought to be limited in scope and stability and to
      be associated with unacceptable complications. Instead, surgically assisted rapid
      maxillary expansion (SA-RME) has been advocated. Five adults with transverse arch
      deficiency are presented to illustrate the feasibility of nonsurgical expansion
      using the Haas appliance. Transmolar expansions of 3.9 to 7.5 mm, sufficient to
      correct the malocclusions, were achieved. Limiting the rate of appliance
      activation is thought to be important to avoid pain, swelling, and ulceration.
      Measurements of molar axial angulation, facial divergence, and clinical crown
      heights demonstrated modest molar tipping, stable mandibular divergence, and only
      minimal gingival recession. Radiographs revealed minimal observable root
      resorption of the maxillary molars and premolars. Contour tracings of the palate
      indicated that most of the correction of the maxillary transarch deficiency
      occurred at the level of the lateral walls of the palate (the alveolar process)
      rather than in the skeletal base of the maxilla. For this reason the technique is
      defined as rapid maxillary alveolar expansion (RMAE). RMAE is an acceptable
      alternative to SA-RME in adults for most cases of maxillary transarch deficiency.
      This article is followed by a commentary by Robert L. Vanarsdall Jr., and by an
      author's response.

PMID- 9267577
TI  - Sutural expansion using rigidly integrated endosseous implants: an experimental
      study in rabbits.
AB  - Rigidly integrated implants offer great promise for orthodontic and orthopedic
      anchorage in the oral and midfacial regions. Rigid anchorage can be used to
      control unwanted tooth movement, provide abutments in edentulous arches, and open
      the vertical dimension of occlusion. To evaluate the use of endosseous implants
      in the midface region, two flanged titanium implants were placed on either side
      of the midnasal suture of 18 New Zealand White rabbits. The rabbits were divided
      into an unloaded control and two experimental groups. One experimental group was
      loaded at 1 Newton (N) and the other at 3 N. All rabbits were euthanized after 12
      weeks of loading. Stereologic point-hit and line-intercept methods were used to
      analyze microradiographic and multiple fluorochrome histology of the suture. All
      implants remained stable during the loading period. The distance between the
      implants increased significantly in the loaded groups compared with the control,
      and was significantly higher in the 3 N group than in the 1 N group. Percent bone
      volume was significantly decreased, while the percent suture volume tended to be
      increased in the loaded groups. Mineral apposition and bone formation rates at
      the sutural surfaces were increased in the loaded groups (P < 0.05), but did not
      differ between loaded groups. These results indicate that relatively low loads (1
      or 3 N) applied to rigidly integrated endosseous implants across an unfused
      suture are satisfactory for achieving expansion under the conditions of this
      study. The 3 N load resulted in slightly more expansion, but did not affect the
      rate of bone formation at the suture.

PMID- 9267580
TI  - Surgically assisted rapid maxillary expansion: a comparison of technique,
      response, and stability.
AB  - The purpose of this study was to evaluate the differences in treatment effects
      between adult patients who underwent surgically assisted rapid maxillary
      expansion employing buccal corticotomies and those who had midpalatal splits as
      well. Responses and sequelae of these treated patients were compared with adults
      who were expanded orthopedically and adults who were treated orthodontically
      without expansion. The sample comprised 37 patients who were expanded and 5
      controls. Dental study casts were taken prior to treatment, at debanding, and at
      the posttreatment follow-up. The results indicated that maxillary expansion in
      adults was predictable and stable, corrected crossbites remained corrected,
      palatal depth was reduced in SARME, palatal width increased (more dramatically in
      patients treated with a combined procedure), and tipping was controlled and
      stable. The long-term buccogingival condition was more acceptable in adults
      expanded with surgical augmentation than in those expanded orthopedically.

PMID- 9267581
TI  - Protein metabolism and therapy in burn injury.

PMID- 9267582
TI  - The assessment of 24-hour energy expenditure in elderly women by minute-by-minute
      heart rate monitoring.
AB  - To test the suitability of minute-by-minute heart rate (HR) monitoring for
      estimating 24-hour total energy expenditure (TEE) in elderly women, 13
      volunteers, mean (SD) age 73 +/- 3 years, participated in this study. Energy
      expenditure during five standardized activities, ranging from sitting quietly to
      walking at 3 km/h, was measured by indirect calorimetry (ventilated hood)
      simultaneously with HR. From these data, individual calibration curves were
      obtained by linear regression. The mean correlation coefficient was 0.89 +/- 0.10
      (range 0.69-0.99). A group calibration curve was also calculated (r = 0.93, p <
      0.02), based on the mean values of energy expenditure during standardized
      activities and simultaneous HR of the 13 subjects. For 3 days, minute-by-minute
      HR was registered continuously. The mean 24-hour HR over these days was 75.7 +/-
      8.5 beats/min. In addition, activity questionnaires were used to calculate energy
      expenditure from time/motion data, using individual measured energy expenditure
      values. TEE calculated from HR using individual calibration curves (8.8 +/- 3.5
      MJ/day) was only moderately correlated (r = 0.60, p < 0.001) with TEE calculated
      from the activity questionnaire (8.6 +/- 0.9 MJ/day). Calculated TEE using the
      group calibration curve was 8.1 +/- 5.2 MJ/day, which was not significantly
      correlated with TEE calculated from the activity questionnaire or with TEE using
      individual calibration curves. The mean values of TEE calculated from the three
      methods were not statistically significantly different. However, individual
      values differed markedly sometimes. Individual physical activity levels
      (TEE/resting metabolic rate), calculated from 24-hour HR monitoring, were
      unreliably high in some subjects. Minute-by-minute HR monitoring did not appear
      to be a valid method for predicting TEE for individuals or small groups.

PMID- 9267583
TI  - Overall and meal-specific macronutrient intake in Belgian primary school
      children.
AB  - In the fall of 1991, dietary intake of 1,321 primary school children aged 6-12
      years was studied in 79 schools in an area called 'South Campine' in Flanders-the
      Dutch-speaking part of Belgium. Assessment of dietary intake was done using the
      '24-hour estimated food record method'. The energy distribution over the
      macronutrients showed no significant difference between boys and girls. On
      average 37.2% (SD 7.88%) of energy came from total fat and 15.4% (SD 3.70%) from
      saturated fatty acids; 49.0% (SD 7.87%) from total carbohydrates with 21.8% (SD
      5.84%) from complex carbohydrates and 27.7% (SD 7.79%) from free sugars. Snacks
      accounted for on average 19.5% (SD 10.83%) of total energy intake; on average
      55.7% (SD 21.22%) of the energy in these snacks was represented by free sugars.
      Lunch and dinner had very high fat contents (around 40% of energy). Already at
      this young age, the dietary pattern is deviating strongly from the recommended
      population nutrient goals.

PMID- 9267585
TI  - Lipid-carbohydrate interactions in post-absorptive non-insulin-dependent diabetic
      patients.
AB  - Substrate competition is an important mechanism of insulin resistance, although
      its role in the post-absorptive hyperglycemia of NIDDM is not clear: lipid
      infusion does not raise plasma glucose levels in normal subjects, and total lipid
      oxidation, the elevation of which is a hallmark of disrupted carbohydrate
      metabolism, is normal in non-insulin-dependent diabetes mellitus (NIDDM). To
      examine further these two arguments against the involvement of lipid-carbohydrate
      interactions in the hyperglycemia of NIDDM, we compared the effect of a 3-hour
      lipid infusion ('Ivelip') on post-absorptive blood glucose levels, plasma lipids
      and respiratory exchanges in 15 patients with NIDDM, with that of an infusion of
      saline in 15 other patients with similar metabolic profiles. The lipid infusion
      significantly slowed the natural post-absorptive decline in blood glucose levels
      (saline -0.47 +/- 0.14 and Ivelip -0.10 +/- 0.12 mmol.l-1.h-1, p < 0.05), with
      marked interindividual differences. Substrate oxidation rates were unchanged
      during saline infusion, and were immediately (within 30 min) and reciprocally
      modified by the lipid infusion (lipid oxidation enhanced: 0.90 +/- 0.14 to 1.06
      +/- 0.13 mg.kg-1.min-1 at time 30 min, p < 0.05; glucose oxidation inhibited:
      1.27 +/- 0.19 to 0.87 +/- 0.18, p < 0.05), but this was not correlated with the
      alteration in blood glucose levels. In contrast, the increase in plasma lipids
      was continuous, and positively correlated with the change in blood glucose levels
      (r = 0.58, p < 0.05 for change of plasma free fatty acids; r = 0.55, p < 0.05 for
      change of plasma triglycerides, TGs). In line with the Randle mechanism, the
      lipid infusion affected oxidation rates, but another mechanism, depending on
      intravascular lipolysis of the infused TGs, was thought to occur in certain
      individuals whose blood glucose levels rose during the infusion.

PMID- 9267584
TI  - Effect of micronutrient supplementation on infection in institutionalized elderly
      subjects: a controlled trial.
AB  - To determine the impact of a trace element and vitamin supplementation on
      infectious morbidity, a double-blind controlled trial was performed on 81 elderly
      subjects in a geriatric center during a 2-year period. Subjects were randomly
      assigned to one of four treatment groups, and received daily: placebo; trace
      elements/zinc 20 mg; selenium 100 micrograms); vitamins (vitamin C 120 mg; beta
      carotene 6 mg; alpha-tocopherol 15 mg); or a combination of trace elements and
      vitamins at equal doses. (1) Before supplementation, low serum values in vitamin
      C, folate, zinc and selenium were observed in more than two thirds of the
      patients. (2) After 6 months of supplementation, a significant increase in
      vitamin and trace element serum levels was obtained in the corresponding
      treatment groups: a plateau was then observed for the whole study. (3) Subjects
      who received trace elements (zinc and selenium) alone or associated with vitamins
      had significantly less infectious events during the 2 years of supplementation.
      These results indicate that supplementation with low doses of vitamins and trace
      elements is able to rapidly correct corresponding deficiencies in the
      institutionalized elderly. Moreover, zinc and selenium reduced infectious events.

PMID- 9267586
TI  - Nutritional value of succinic acid monoethyl ester in starvation.
AB  - Rats were fasted for 48 h, but infused with either NaCl or the sodium salt of
      monoethyl succinic acid (EMS), both delivered at a rate of 80 mumol/g body weight
      per day. The infusion of EMS, as compared to NaCl, failed to affect paraovarian
      adipose tissue or liver weight, liver or muscle glycogen, and insulinemia. It
      accentuated the starvation-induced fall in body weight, and decreased both liver
      and muscle protein content. Nevertheless, the succinate ester increased plasma D
      glucose concentration, delayed the rise in ketonemia, maintained a higher
      glucokinase/hexokinase activity ratio in liver and pancreatic islets, and allowed
      for a more efficient stimulation of insulin release by D-glucose or 2
      ketoisocaproate in isolated pancreatic islets. These findings indicate that
      monoethyl succinate displays a significant nutritional value when infused in
      starved rats.

PMID- 9267588
TI  - Fuzzy set theory in medicine.
AB  - Indeed, the complexity of biological systems may force us to alter in radical
      ways our traditional approaches to the analysis of such systems. Thus, we may
      have to accept as unavoidable a substantial degree of fuzziness in the
      description of the behavior of biological systems as well as in their
      characterization. This fuzziness, distasteful though it may be, is the price we
      have to pay for the ineffectiveness of precise mathematical techniques in dealing
      with systems comprising a very large number of interacting elements or involving
      a large number of variables in their decision trees.

PMID- 9267587
TI  - Changes in biochemical indicators of iron status during iron repletion and
      depletion in monkeys.
AB  - Different modes of iron depletion and repletion were studied in monkeys to
      understand the sequential changes in and the relative importance of different
      biochemical indicators of iron status. Six control monkeys were divided into two
      groups, one was fed an iron-deficient diet (group 1) and the other underwent
      phlebotomy in addition to receiving an iron-deficient diet (group 2). Previously
      iron-depleted monkeys were subdivided into 4 groups of 3 animals each. While one
      group was continued on the iron-deficient diet (group 3), the second group
      received parenteral iron (group 4), the third group (group 5) received a
      sufficient-iron-containing diet, and the fourth group was fed 50% of the iron
      requirement. All indicators of iron status like hemoglobin (Hb), erythrocyte
      protoporphyrin (EPP), serum transferrin saturation and serum ferritin were
      monitored periodically, in addition to liver and bone marrow iron. all the
      indicators except serum ferritin and liver iron showed a decrease in group 2. On
      the other hand, animals receiving parenteral iron (group 4) showed an increase in
      all the parameters except serum ferritin. The dietary supplementation produced an
      increase in Hb and a decrease in EPP only (groups 5 and 6). There was a
      significant positive correlation between changes in bone marrow iron and Hb
      concentration depending on the severity of depletion and repletion. Both serum
      ferritin and liver iron did not respond to changes in dietary iron. Another
      parameter which responded to repletion was EPP. Serum ferritin and liver iron did
      not respond to changes in dietary iron or was not sensitive to subclinical iron
      deficiency. The results indicate that change in Hb is more sensitive to detect
      the deficiency of iron. It was also observed that different parameters respond
      variably under different modes of depletion and repletion.

PMID- 9267589
TI  - Fuzzy logic for model adaptation of a pharmacokinetic-based closed loop delivery
      system for pancuronium.
AB  - In this paper, we investigate the ability of fuzzy to adapt the parameters of a
      pharmacokinetic and pharmacodynamic model-based controller for the delivery of
      the muscle relaxant pancuronium. The system uses the model to control the rate of
      drug delivery and uses feedback from a sensor which measures muscle relaxation
      level to adapt the model using fuzzy logic. The control strategy administers mini
      bolus doses of pancuronium and modulates the magnitude and time interval between
      the bolus doses to maintain a patient's muscle relaxation within an allowable
      range specified by the user. Before each new dose is given, the fuzzy logic
      adaptation scheme uses the error between the predicted patient response and the
      measured response to adapt the model. The system was tested using computer
      simulation by varying the parameters of the model by 50% from their nominal
      values. It was also evaluated in a clinical trial of five patients undergoing
      surgical procedures lasting 5 h or longer.

PMID- 9267590
TI  - Design and validation of an intelligent patient monitoring and alarm system based
      on a fuzzy logic process model.
AB  - The process of patient care performed by an anaesthesiologist during high
      invasive surgery requires fundamental knowledge of the physiologic processes and
      a long standing experience in patient management to cope with the inter
      individual variability of the patients. Biomedical engineering research improves
      the patient monitoring task by providing technical devices to measure a large
      number of a patient's vital parameters. These measurements improve the safety of
      the patient during the surgical procedure, because pathological states can be
      recognised earlier, but may also lead to an increased cognitive load of the
      physician. In order to reduce cognitive strain and to support intra-operative
      monitoring for the anaesthesiologist an intelligent patient monitoring and alarm
      system has been proposed and implemented which evaluates a patient's haemodynamic
      state on the basis of a current vital parameter constellation with a knowledge
      based approach. In this paper general design aspects and evaluation of the
      intelligent patient monitoring and alarm system in the operating theatre are
      described. The validation of the inference engine of the intelligent patient
      monitoring and alarm system was performed in two steps. Firstly, the knowledge
      base was validated with real patient data which was acquired online in the
      operating theatre. Secondly, a research prototype of the whole system was
      implemented in the operating theatre. In the first step, the anaesthetists were
      asked to enter a state variable evaluation before a drug application or any other
      intervention on the patient into a recording system. These state variable
      evaluations were compared to those generated by the intelligent alarm system on
      the same vital parameter constellations. Altogether 641 state variable
      evaluations were entered by six different physicians. In total, the sensitivity
      of alarm recognition is 99.3%, the specificity is 66% and the predictability is
      45%. The second step was performed using a research prototype of the system in
      anaesthesiological routine. The evaluation of 684 events yielded a sensitivity,
      specificity and predictability of the alarm recognition of more than 99%.

PMID- 9267591
TI  - Lightweight fuzzy processes in clinical computing.
AB  - In spite of advances in computing hardware, many hospitals still have a hard time
      finding extra capacity in their production clinical information system to run
      artificial intelligence (AI) modules, for example: to support real-time drug-drug
      or drug-lab interactions; to track infection trends; to monitor compliance with
      case specific clinical guidelines; or to monitor/ control biomedical devices like
      an intelligent ventilator. Historically, adding AI functionality was not a major
      design concern when a typical clinical system is originally specified. AI
      technology is usually retrofitted 'on top of the old system' or 'run off line' in
      tandem with the old system to ensure that the routine work load would still get
      done (with as little impact from the AI side as possible). To compound the burden
      on system performance, most institutions have witnessed a long and increasing
      trend for intramural and extramural reporting, (e.g. the collection of data for a
      quality-control report in microbiology, or a meta-analysis of a suite of coronary
      artery bypass grafts techniques, etc.) and these place an ever-growing burden on
      typical the computer system's performance. We discuss a promising approach to
      adding extra AI processing power to a heavily-used system based on the notion
      'lightweight fuzzy processing (LFP)', that is, fuzzy modules designed from the
      outset to impose a small computational load. A formal model for a useful subclass
      of fuzzy systems is defined below and is used as a framework for the automated
      generation of LFPs. By seeking to reduce the arithmetic complexity of the model
      (a hand-crafted process) and the data complexity of the model (an automated
      process), we show how LFPs can be generated for three sample datasets of clinical
      relevance.

PMID- 9267592
TI  - Fuzzy logic in computer-aided breast cancer diagnosis: analysis of lobulation.
AB  - This paper illustrates how a fuzzy logic approach can be used to formalize terms
      in the American College of Radiology (ACR) Breast Imaging Lexicon. In current
      practice, radiologists make a relatively subjective determination for many terms
      from the lexicon related to breast cancer diagnosis. Lobulation and
      microlobulation of nodules are two important features in the ACR lexicon. We
      offer an approach for formalizing the distinction of these features and also
      formalize the description of intermediate cases between lobulated and
      microlobulated masses. In this paper it is shown that fuzzy logic can be an
      effective tool in dealing with this kind of problem. The proposed formalization
      creates a basis for the next three steps (i) extended verification with blinded
      comparison studies. (ii) the automatic extraction of the related primitives from
      the image, and (iii) the detection of lobulated and microlobulated masses based
      on these primitives.

PMID- 9267593
TI  - Should we be using polyhexamethylene biguanide to treat Acanthamoeba keratitis?

PMID- 9267594
TI  - Ocular gene therapy: the basic science and current state of research.
AB  - Recent technical advances have led to the demonstration of the molecular basis of
      many genetic eye diseases. Methods now in use have been able to both suppress and
      insert genes in vitro and in vivo in ocular cells. The combination of this new
      knowledge and these techniques offers the potential for a new therapeutic
      approach to diseases that currently have no treatments. The scientific basis of
      gene therapy is introduced and then the current state of research is discussed in
      relation to the eye and ocular tissues.

PMID- 9267595
TI  - The cellular mechanism underlying neuronal degeneration in glaucoma: parallels
      with Alzheimer's disease.
AB  - Evidence is presented that the characteristic pattern of neuronal degeneration
      associated with glaucoma is due to a combination of the persistent physical
      damage to axons at the level of the lamina cribrosa and the associated neuronal
      reaction to this kind of trauma. The class of neuronal cytoskeletal proteins
      known as the neurofilament triplet are crucially involved in the reaction to
      physical damage and the selective localization of these proteins to larger
      retinal ganglion cells may underlie their susceptibility to eventual
      degeneration. The appearance of glaucoma-like neuronal pathology in Alzheimer's
      disease may follow the reaction of neurofilament-containing retinal ganglion
      neurons to persistent damage to their axons by beta-amyloid plaque formation in
      subcortical visual centers.

PMID- 9267596
TI  - Extended wear disposable soft contact lenses as an alternative to photorefractive
      keratectomy: report of 4 years experience.
AB  - PURPOSE: To establish whether, in a well-informed population, the use of extended
      wear disposable soft contact lenses (EWDSCL) poses an unacceptable risk to vision
      and corneal health due to complications associated with their use. METHODS: A 4
      year retrospective review of EWDSCL, involving 371 patients in Melbourne from a
      single general ophthalmology practice. The important aspects of this group were
      that all patients were given written instructions about the methods of ensuring
      initial and ongoing cleanliness of lenses, no lenses were cleaned and reinserted,
      and no solutions other than the saline in the original packaging, and comfort
      crops, were used. Two types of EWDSCL were used in powers from -9.0 to +6.0 D,
      and with an initial aim of 4 weeks uninterrupted extended wear. Follow-up was
      from 2 to 52 months, with an average of 24 months. RESULTS: Of the 354 patients
      followed up, 236 (66%) regularly wore them on an extended overnight basis, and of
      these 180 (76%) wore them for the suggested 4 week period before renewal of
      lenses. In the 471 eyes of 236 patients, adverse reactions occurred at the
      following rates, marginal infiltrates (12 cases, 2.5%); corneal oedema (10 cases,
      2%) peripheral corneal vascularization (2 cases, 0.4%); and presumed infective
      keratitis (1 case, 0.2%). No eyes lost one or more lines of Snellen acuity.
      CONCLUSIONS: When disposable soft contact lenses do not come into contact with
      cleaning solutions, saline from bottles or aerosol cans, or storage cases, their
      use on an extended wear basis (up to 4 weeks continuous) appears to be associated
      with a low risk of minor or major complications. The results of this review
      indicate that controlled usage of EWDSCL is safer than previous reports have
      indicated.

PMID- 9267598
TI  - Visual acuity in an Australian aboriginal population.
AB  - BACKGROUND: Australia is a developed country. However, Aboriginal Australians
      have rates of blindness comparable to Third World countries. There have been well
      funded eye health programs for 15 years in Central Australia. This paper examines
      if there has been an improvement in visual disability of one traditional group of
      Aboriginal Australians. METHODS: Results from an eye health survey of the Anangu
      Pitjantjatjara of South Australia in 1990 are presented. These data are compared
      with results for 'blindness' and 'poor vision' from a national survey undertaken
      in 1976. The two surveys were comparable in design, both were cross-sectional
      population-based prevalence surveys. Prevalence rates were adjusted for the size
      of the source population. RESULTS: Young rural Aboriginal Australians have good
      visual acuity. Low vision and blindness (WHO definitions) occur in 19.6% and
      10.4% of 60+ year olds, respectively. Women were more likely than men to be blind
      or have low vision (OR = 1.93; 1.06-3.58). There was a decline in 'poor vision'
      between surveys (OR = 2.86; 1.86-4.75) but not in 'blindness'. CONCLUSION:
      Although there has been a reduction in the prevalence of visual disability in
      rural Aboriginal Australians, improvements in the provision of eye care for the
      elderly need to occur.

PMID- 9267597
TI  - Atypical choristomatous cysts of the orbit.
AB  - BACKGROUND: The commonset choristomatous cysts of the orbit are dermoid and
      epidermoid cysts, which are lined by kerantinizing squamous epithelium. They
      typically occur in the superior orbit, most commonly superotemporally. Other
      types, lined by different epithelia, and other orbital sites are much less
      common. METHODS: Five cases of atypical orbita cystic choristomas that presented
      over the past 6 years are reported. The clinical and radiological features,
      surgical approach and findings, and histology, are described. Similar cases from
      the literature are reviewed and possible aetiology discussed. RESULTS: Four of
      the cysts were lined by a non-keratinizing epithelium resembling conjunctiva; two
      had adnexal structures in their walls. Compared with typical dermoid and
      epidermoid cysts, these 'conjunctival dermoids' and 'conjunctival cysts' of the
      orbit tended to present later in life, none were associated with bony defects,
      and three of the four occurred in the superomedial quadrant. One case occurred
      inferiorly, a rare site for orbital conjunctival dermoids and cysts, or typical
      dermoids and epidermoids. The fifth case, also inferior, is an example of a cyst
      within choristomatous lacrimal tissue. CONCLUSION: Choristomatous cysts of the
      orbit may occur with non-keratinizing epithelial linings, and such cysts tend to
      differ clinically from the commoner dermoids and epidermoids. They may also occur
      in atypical sites such as the inferior orbit.

PMID- 9267599
TI  - Intravitreal cilia in phakic penetrating eye injury.
AB  - BACKGROUND: Intraocular cilia present clinical perplexity due to their
      radiolucency, the extremely variable ocular response to such cilia, and the
      inadvisability of using MRI in cases of suspected metallic intraocular foreign
      bodies (IOFB). METHODS: Two cases of intravitreal cilia associated with phakic
      penetrating eye injury are described where preoperative CT scan revealed no
      retained IOFB. RESULTS: B-scan ultrasonography detected intravitreal cilia in one
      patient and raised this suspicion in the other. One patient presented with
      endophthalmitis unresponsive to intravitreal antibiotics, the other with culture
      negative anterior uveitis. Both underwent vitrectomy and removal of cilia.
      CONCLUSIONS: Intravitreal cilia should be considered in penetrating eye injuries
      even in phakic eyes with no radiological evidence of IOFB, especially if
      associated with endophthalmitis. B-scan ultrasonography may aid detection of
      intravitreal cilia and thus alter clinical management.

PMID- 9267600
TI  - Optic disc haemorrhages and vascular abnormalities in a glaucoma population.
AB  - PURPOSE: To retrospectively examine the optic disc photographs of a glaucoma
      population for optic disc haemorrhages, vascular occlusions and vascular
      abnormalities. METHODS: The optic disc photographs of 906 eyes of glaucoma and
      suspect glaucoma patients were examined. Optic disc photographs were taken
      annually, where possible, with the follow-up period varying between 1 and 14
      years duration (mean, 2.89). Glaucoma patients are regularly reviewed every 4-6
      months and glaucoma suspects every 1-2 years, depending on the ophthalmologist.
      Low-tension glaucoma patients were reviewed more frequently (mean, every 2.6
      months). The results of the findings were compared to a control group of 39
      subjects with a mean follow-up period of 7 years, using Fisher's exact test.
      RESULTS: It was found that during the period under review, 7.4% (n = 67) of eyes
      had optic disc haemorrhages. The highest frequency of optic disc haemorrhages
      (37.5%) was found in the low tension glaucoma group (P = 0.0001) followed by 11%
      of primary open-angle glaucoma eyes (P = 0.03). In the normal group there were
      three eyes with optic disc haemorrhages and one with a disc collateral, which
      constitutes 5.1% vascular changes in this sub-group. Of the study eyes 2.8% had
      central retinal vein occlusions, 1.3% branch vein occlusion, 1.2% disc vessel
      abnormalities (loops) and 1.1% disc collaterals. Discrete nerve fibre layer
      haemorrhages and microaneurysms were found in 0.8% and 1.8% of eyes,
      respectively. CONCLUSIONS: A total of 16.8% of the eyes observed in this study
      had either disc haemorrhages or vascular changes. The underlying trend of
      vascular and haemorrhagic changes in glaucoma are demonstrated in this sample,
      which is in general agreement with previous studies. The high percentage of optic
      disc haemorrhages in low tension glaucoma is highlighted. The presence of
      microaneurysms and nerve fibre layer haemorrhages is interesting but of unknown
      significance.

PMID- 9267601
TI  - Changing indications for penetrating keratoplasty: a newly developed country's
      experience.
AB  - PURPOSE: To study the changing indications for penetrating keratoplasty in
      Singapore and compare local indications with developed countries with established
      corneal graft programs. METHODS: A descriptive study of all penetrating
      keratoplasty cases performed in the Singapore National Eye Center over a 5 year
      period, from 1 January 1991 to 31 December 1995 using records of the Singapore
      Eye Bank registry. RESULTS: A total of 327 penetrating keratoplasties were
      performed. Bullous keratopathy was the indication in more than a quarter of all
      cases (26.3%). Aphakic bullous keratopathy (11.6%) and pseudophakic bullous
      keratopathy (11.3%) accounted for the majority of the bullous keratopathy cases.
      The other leading indications were regrafts (11.9%), corneal dystrophies (10.4%),
      traumatic scarring (10.1%) and keratoconus (9.8%). A higher proportion of aphakic
      and pseudophakic bullous keratopathy as well as regrafts was noted in this series
      compared to a previous report on corneal transplantation in the 1980s. A rising
      indication rate of pseudophakic bullous keratopathy, in conjunction with a
      declining indication rate of herpetic keratitis was observed over the 5 year
      study period. CONCLUSIONS: The indications for penetrating keratoplasty in
      Singapore appear to follow the trend seen in developed Western countries over the
      past few decades.

PMID- 9267602
TI  - Profile of ocular trauma in Papua New Guinea.
AB  - BACKGROUND: Ocular trauma is a significant cause of blindness in Papua New Guinea
      (PNG). This study was done to determine the pattern and rates of ocular and
      adnexal injuries so as to determine the size and extent of the problem. METHODS:
      A retrospective study of 4157 cases presenting with ocular trauma in three
      regions of PNG was carried out. The data were analysed with respect to the age,
      sex, province, type and cause of injury, time interval between injury and
      presentation to the hospital and the final visual outcome after treatment.
      RESULTS: Ocular trauma rates in PNG were alarmingly high (39.1 per 100,000). The
      commonest cause of injury in the younger age group was due to lime. Alcohol
      related violence and fights resulted in injuries in the adult age group. Most of
      the injuries were grievous and 60.7% of patients were left with a visual acuity
      of less than 6/60 in the injured eye. In addition, 78.7% of the patients were
      under 30 years of age. CONCLUSIONS: Ocular injuries in PNG are an important cause
      of visual disability. Some specific injuries, such as those due to lime in
      children, can easily be prevented by health education.

PMID- 9267603
TI  - Orbital colour Doppler imaging in chronic ocular ischaemic syndrome.
AB  - BACKGROUND: The clinical syndrome of chronic ocular ischaemia may be difficult to
      diagnose due to its wide range of non-specific presentations, and its diagnosis
      often implies the presence of underlying severe carotid occlusive disease. Colour
      Doppler imaging (CDI), a recent advance in ultrasonography that allows for colour
      encoded blood flow data of a vascular structure to be displayed simultaneously on
      a conventional real-time gray-scale B mode image, has been used in the assessment
      of ocular and orbital vasculature. METHOD: Four patients with chronic ocular
      ischaemic syndrome whose diagnoses were aided by CDI are presented. RESULTS:
      Orbital CDI was successful in confirming the diagnosis in all four cases.
      Reversal of blood flow in the ophthalmic arteries was demonstrated. Central
      retinal vessels were not detected with CDI in all four patients with complete
      occlusion of the ipsilateral internal carotid artery. One of the four patients
      had intermittent reversal of ophthalmic arterial flow ipsilateral to the 60%
      stenosed interna carotid artery. CONCLUSION: This non-invasive technique is an
      excellent alternative to invasive vascular studies such as angiography for the
      diagnosis and evaluation of the chronic ocular ischaemic syndrome.

PMID- 9267604
TI  - Congenital optic pits and central serous chorioretinopathy.
AB  - PURPOSE: The reporting of the occurrence of central serous chorioretinopathy in a
      patient with congenital optic pits. METHODS: A 31-year-old man complained of
      blurred vision in the right eye for 1 week. He had a visual acuity of 20/25 in
      the right eye. He underwent ophthalmoscopy and fluorescein angiography. RESULTS:
      Ophthalmoscopy revealed serous detachment of macula with its margin not adjacent
      to the margin of optic disc. Fluorescein angiography showed a typical ink blot
      appearance of dye leakage. CONCLUSIONS: Central serous chorioretinopathy can
      occur in the patient with congenital optic pits. Detailed ophthalmoscopic and
      fluorescein angiographic studies are necessary to establish the diagnosis of
      optic pits associated with macular detachment. Various mechanisms have been
      reported to explain the serous macular detachment in patients with optic pits
      including vitreous and cerebrospinal fluid leakage through the optic pit and from
      there into the subretinal space. The present case further denotes that central
      serous chorioretinopathy in the presence of optic pits can be due to leakage from
      the retinal pigment epithelium.

PMID- 9267605
TI  - Meningococcal conjunctivitis.
AB  - BACKGROUND: Primary meningococcal conjunctivitis is a rare condition that can
      have devastating ocular and systemic complications. METHODS: Review of the case
      records. CONCLUSIONS: Appropriate Gram stain and cultures should be obtained in
      cases of hyperacute conjunctivitis, especially in young patients, and systemic
      antibiotics should be initiated promptly where Gram-negative diplococci are found
      and prophylaxis for close contacts considered in Neisseria meningitidis
      conjunctivitis.

PMID- 9267606
TI  - Scedosporium prolificans corneoscleritis: a successful outcome.
AB  - BACKGROUND: A case of Scedosporium prolificans corneoscleritis is reported in a
      patient who had developed scleral necrosis following pterygium surgery, with
      adjunctive beta-irradiation. This fungus has been reported to be the causative
      organism in only two previous cases of corneoscleritis. METHODS: The patient
      presented with signs and symptoms typical of corneoscleritis. When the fungus was
      isolated from a biopsy specimen, aggressive scleral debridement was carried out
      and intensive antifungal therapy was instigated. RESULTS: After a prolonged
      course, the eye was rendered sterile. CONCLUSION: Early conjunctival recession
      and aggressive scleral debridement combined with intensive instillation of
      antifungals are crucial to the successful management of fungal corneoscleritis.

PMID- 9267607
TI  - A dental prosthesis to close the palpebral fissure.

PMID- 9267608
TI  - Dislocation of the globe into the ethmoid sinuses.

PMID- 9267609
TI  - Pythium insidiosum keratitis.
AB  - A case of Pythium insidiosum keratitis is described. It is an unusual organism
      that is difficult to isolate. Cases in animals and humans have been reported from
      tropical and subtropical parts of the world but this is the first case from a
      temperate region and was acquired from a hot pool. Although resembling a fungus,
      it is insensitive to all antifungals and requires wide surgical excision for
      cure.

PMID- 9267610
TI  - Nanophthalmos with longstanding choroidal effusion and serous retinal detachment.
AB  - PURPOSE: To report a typical case of nanophthalmos with uveal effusion and local
      serous retinal detachment followed for 1 year. METHODS: Clinical ocular
      examinations included vision, refraction, corneal diameter, anterior chamber
      depth, intraocular pressure, fundoscopy, A/B scan ultrasonography and gonioscopy.
      RESULTS: Both eyes were hypermetropic with small corneas and shallow anterior
      chambers. Decreased axial length and thickened sclera were also found. There were
      peripheral choroidal effusions and local serous retinal detachments as well. The
      patient declined any surgery that was offered. No significant change in either
      eye was found after 1 year follow-up. CONCLUSION: This case illustrates that the
      progress of choroidal effusion and retinal detachment in nanophthalmos may be
      very slow and even non-progressive for at least 1 year. In these cases
      sclerectomy and or sclerotomy may be delayed without undue immediate risk to the
      vision.

PMID- 9267611
TI  - Cataract surgery reduces subjective visual disability.
AB  - PURPOSE: The present study examines the impact of cataract on visual disability
      (VD) and how cataract surgery alters VD. METHODS: Fifty-six patients were
      assessed pre- and at 3 months post cataract surgery. Cataract severity was
      measured with the Lens Opacities Classification System III (LOCS III). Visual
      disability was assessed by questionnaire. The relationship between LOCS III
      scores and total VD score was examined with linear regression. Repeated measures
      analysis of variance was used to determine whether the pre- and postoperative VD
      scores were different. RESULTS: The VD score was found to relate more closely to
      the LOCS III score in the least affected eye than in the most affected eye. The
      VD score is related to nuclear opacity (P = 0.01), and posterior subcapsular
      cataract (PSC; P = 0.0004), but not to cortical cataract (P = 0.51) (r2 = 0.43).
      The VD score is significantly greater before surgery (mean +/- SD) 1.81 +/- 0.67)
      than after (1.19 +/- 0.21; P < 0.001). CONCLUSIONS: Nuclear and PSC cataracts
      cause more visual disability than cortical cataracts. Visual disability is
      significantly reduced by cataract surgery.

PMID- 9267612
TI  - Changes in the interpupillary distance with age and its effect on the near fusion
      free position.
AB  - PURPOSE: The effect of the rate of the interpupillary distance (IPD) change with
      age on the near fusion free position was investigated in the present study.
      METHODS: Three hundred and fifty-two children aged from 2 to 16 years of age were
      tested. Interpupillary distance was estimated with a modified Viktorin's method
      and the near fusion free position was measured with a modified Maddox Wing.
      RESULTS: The results reveal a significant difference in IPD growth rate between
      females and males and between children aged below and above 5 years. Most
      children below 5 years of age were orthophoric, but heterophoria became more
      common above 5 years of age. CONCLUSION: The present study suggests that the
      oculomotor control system for convergence can compensate for age changes in IPD.

PMID- 9267613
TI  - A computer-generated test of acuity for multi-handicapped children.
AB  - Assessment of visual function in severely intellectually handicapped children is
      difficult but necessary for educational purposes. The difficulties encountered
      include: lack of literacy skills; lack of verbal and fine motor skills; and low
      interest level of the optotypes. A computer-generated test has been developed
      that helps overcome these difficulties. This test presents pictures equivalent in
      line width to Snellen, which are manipulated on screen to provide movement and
      change of size to facilitate non-verbal responses and to increase interest level.
      Evaluation trials were conducted with 96 cognitively normal children and 37 multi
      handicapped children. The computer test facilitated testing of significantly more
      of the multi-handicapped children. Data from both trial groups indicated a good
      positive correlation between the computer test and a standard optotype test.
      Further refinement and evaluation of this computer test is continuing.

PMID- 9267614
TI  - Gender, oestrogen, hormone replacement and age-related macular degeneration:
      results from the Blue Mountains Eye Study.
AB  - PURPOSE: To determine whether females have a higher age-specific age-related
      maculopathy prevalence than males; whether there is an increased risk of age
      related macular degeneration (AMD) with early menopause; and whether there is a
      decreased risk of AMD with use of hormone replacement therapy (HRT). METHODS:
      Pooled data from three study populations that have used similar AMD diagnostic
      criteria were used to answer the first hypothesis: the Beaver Dam Eye Study
      (BDES), the Rotterdam study of the elderly, and the Blue Mountains Eye Study
      (BMES). The BMES population was used to answer the second and third hypotheses.
      This population included residents aged 49 or older with 2072 women
      participating, of whom 1899 postmenopausal women answered questions about
      menopause, menarche and HRT. AMD was diagnosed from graded retinal photographs
      using modified international criteria. RESULTS: The overall pooled odds ratio
      (OR) for association between sex and AMD revealed a significant increase in AMD
      prevalence among females compared with males, adjusting for 10-year age
      categories, OR = 1.15 (1.10-1.21), with no significant heterogeneity between
      studies. A significant decrease in the odds of early AMD with increasing years
      from menarche to menopause was observed. CONCLUSIONS: The results suggest that
      females may have a higher risk of AMD. The significant decrease in early AMD with
      increasing years from menarche to menopause supports the concept that a shorter
      duration of oestrogen production may increase risk of AMD.

PMID- 9267615
TI  - Detection and specificity of anti-Staphylococcus intermedius secretory IgA in
      human tears.
AB  - PURPOSE: Secretory IgA (sIgA) is the predominant immunoglobulin present in tears
      that protects the ocular surface against various antigens. Staphylococcus
      intermedius is a member of the normal ocular microbiota. METHODS: The presence
      and the specificity of immunoglobulin A to S. intermedius was determined by
      fluorescent assay, ELISA and western blots. RESULTS: Three immunodominant
      antigens of S. intermedius were detected of 145, 127 and 61 kDa. Staphylococcus
      intermedius-specific IgA cross reacted with Staphylococcus aureus but not with
      Gram negative bacteria. CONCLUSIONS: This indicates that specific IgA may play an
      important role in the protection of the eye by limiting the levels of Gram
      positive normal microbiota and defending against the more pathogenic S. aureus.

PMID- 9267616
TI  - Interactions between the constitutive host defences of tears and Staphylococcus
      epidermidis.
AB  - As part of the normal microbiota of the external eye, Staphylococcus epidermidis
      has probably developed strategies to overcome tear defences. The interaction of
      this bacteria with constitutive tear proteins was examined. Isolates of S.
      epidermidis grown in 10% serum or artificial tear fluid containing lysozyme or
      lactoferrin were resistant to the action of these proteins. Using ELISA, cell
      wall binding of C3, vitronectin and lactoferrin differed quantitatively between
      strains and in closed-eye compared to open-eye conditions. No differences were
      observed between ocular and non-ocular strains. This suggests that ocular
      isolates originate from the general host microbiota and S. epidermidis isolates
      are resistant to individual constitutive tear proteins.

PMID- 9267617
TI  - Growth of gram-negative bacteria in a simulated ocular environment.
AB  - PURPOSE: Gram-negative bacteria are major pathogens in the ocular environment,
      especially when contact lenses are worn. The source of many of these organisms,
      including Pseudomonas aeruginosa, is thought to be environmental. METHODS: A
      defined medium is described here that resembles both tear fluid and the
      environment they are derived from. RESULTS: Gram-negative ocular bacteria were
      found to grow successfully in this medium. Bactericidal tear proteins were added
      to this medium and pathogenic strains were not only able to resist their effects
      but were able to use them for growth. CONCLUSION: Utilization of tear proteins
      for growth may be an important virulence factor of pathogenic bacteria in the
      ocular environment.

PMID- 9267618
TI  - Presence of inflammatory mediators in the tears of contact lens wearers and non
      contact lens wearers.
AB  - The present studies have demonstrated the levels of N-methyl histamine in tears
      from normal physiological states, pathological states and contact lens wear.
      Histamine was significantly increased in closed eye tears compared with both open
      and reflex tears. Tears from other ocular conditions had low levels of histamine
      except for environmental hypersensitivity, which contained significantly elevated
      levels compared to normal tear types. Interestingly, tears from asymptomatic
      contact lens wearers had significant levels of histamine whereas tears from
      contact lens adverse events had lower levels, possibly reflecting a change in
      histamine metabolism.

PMID- 9267619
TI  - Role of tear fluid in the growth of gram-negative bacteria on contact lenses.
AB  - Incidents of CLARE (contact lens induced acute red eye) are associated with high
      numbers of Gram-negative bacteria on the lens surface. This study found that most
      strains of bacteria implicated in CLARE adhere poorly to the lens surface
      regardless of whether the lens surface was clean or had been worn in the eye. The
      high numbers of bacteria on the lens surface result from bacterial growth on the
      lens surface after adhesion has occurred. Using an artificial tear formulation
      and real tears, this study demonstrated that the tear fluid provides the
      necessary nutrients required for bacterial growth.

PMID- 9267620
TI  - Ocular microbiota and polymorphonuclear leucocyte recruitment during overnight
      contact lens wear.
AB  - Bacterial colonization of the ocular surface and contact lens (CL) and
      recruitment of polymorphonuclear leucocytes (PMN) during overnight CL wear was
      examined in 11 asymptomatic wearers. The ocular surface was more frequently
      colonized than the CL, with commensal bacteria (P < 0.05). Following sleep, more
      bacteria were recovered from the CL compared with daily use (P < 0.05), and fewer
      PMN were recruited compared to sleep without CL wear (P < 0.05). Overnight CL
      wear may inhibit physiological PMN recruitment to the cornea by preventing their
      access, by modifying the chemotactic signal or by altering the activation state
      of the recruited cells.

PMID- 9267621
TI  - Effect of hydrogel lens wear on the major tear proteins during extended wear.
AB  - PURPOSE: The purpose of the present study was to determine the whether contact
      lens wear disturbed the levels of tear proteins and to further determine whether
      this was a transient or continuous disruption. METHODS: Lactoferrin, lysozyme and
      albumin were quantitated from tears of neophyte patients and were compared with
      the levels of these proteins in contact lens wearers after one and six nights and
      6 months of extended wear. The quantitation of these tear proteins was performed
      by sandwich ELISA and turbidimetric assay. RESULTS: Results showed that there
      were no statistically significant changes in the concentration of any of the
      proteins investigated. CONCLUSIONS: Extended wear of hydrogel lenses does not
      appear to alter the concentration of the major tear film proteins, indicating
      that the tear film is constantly replenished to maintain protein levels, which
      are depleted due to protein adsorption to the lens surface.

PMID- 9267622
TI  - Adhesion and growth of Serratia marcescens on artificial closed eye tears soaked
      hydrogel contact lenses.
AB  - The adhesion to hydrogel contact lenses and growth of Serratia marcescens on
      artificial tear fluid (ATF) soaked lenses was investigated. Results indicated
      that a corneal ulcer isolate adhered more avidly to lenses; ATF increased
      adhesion for all strains tested. The contact lens induced acute red eye (CLARE)
      isolate adhered poorly, however, it grew to a larger extent on ATF-coated lenses.
      The ability of the corneal ulcer isolate to adhere to lenses may be an important
      factor in its pathogenicity whereas the ability of the CLARE isolate to grow on
      the lens in the presence of antimicrobial tear proteins may be important in the
      development of inflammation.

PMID- 9267623
TI  - Modulation of cytokine production from an EpiOcular corneal cell culture model in
      response to Staphylococcus aureus superantigen.
AB  - The present study investigated the hypothesis that Staphylococcus aureus
      enterotoxin B (SEB) produces epithelial cell death and releases inflammatory
      cytokines that produce stromal infiltration during contact lens induced
      peripheral ulceration. Epithelial cells were incubated with different doses of
      SEB for various time periods. Culture supernatants were assayed for cytokines IL
      1 beta, IL-6 and chemotactic agents IL-8 and LTB4 SEB induced the production of
      IL-1 beta and IL-8. Epithelial cells exposed for longer periods (48 h) with low
      concentrations of SEB produced significantly higher levels (P < 0.02) of IL-1
      beta and IL-8 (P < 0.05) compared to a 24 h exposure. SEB did not induce the
      production of IL-6 and LTB4.

PMID- 9267624
TI  - Effects of biologically modified surfaces of synthetic lenticules on corneal
      epithelialization in vivo.
AB  - PURPOSE: The present study investigated the association of extracellular matrix
      (ECM) glycoprotein coatings with initial epithelialization of artificial
      lenticules in vivo. METHODS: Collagen I, collagen IV, ECM and fibronectin were
      individually coated onto the surface of polycarbonate membranes. The membranes
      were then implanted in the anterior stroma of adult cats and were clinically
      assessed for rapidity and extent of epithelialization and the persistence of
      epithelial attachment. RESULTS/CONCLUSIONS: It was demonstrated that membrane
      surfaces modified by collagen I, collagen IV and ECM consistently supported
      initial migration and attachment of corneal epithelial cells and that the surface
      modified with collagen I performed best.

PMID- 9267625
TI  - Keratoprosthesis results in animals: an update.
AB  - BACKGROUND: The report presented is an update on continuing development work on
      modified PHEMA core-and-shirt KPros in animals. METHODS: Two variations (improved
      wet-eye, and dry-eye) of a prototype core-and-skirt Chirila KPro are described.
      The clinical success rate on implantation of these versions of the Chirila KPro
      was assessed. RESULTS: It was found that a significant improvement in retention
      rate was shown in the improved model but that the dry-eye model failed early in
      two of the three implanted. CONCLUSIONS: The significance of the improved
      strength and the reasons for disappointing results with the early dry-eye KPros
      are discussed. Ongoing work is briefly outlined.

PMID- 9267626
TI  - Fourier transformation of corneal topography data.
AB  - BACKGROUND: The clinical interpretation of corneal topography power maps has
      progressed through the development of both qualitative pattern classification
      systems and a range of quantitative descriptors. Although a number of different
      indices have been described, they do not all possess obvious clinical utility.
      METHODS/RESULTS: Fourier series analysis decomposes any circumferential
      fluctuations in corneal power into various components that have direct clinical
      correlates. The zero frequency and two-cycle components, which represent
      spherical equivalent and regular astigmatism, respectively, are analogous to
      keratometric spherical (equivalent) and astigmatic powers. The other Fourier
      components have no keratometric equivalent but have distinct clinical value.
      Decentration is a tilt of the cornea with respect to the videokeratoscope axis
      and irregular astigmatism is the sinusoidal variation in power that cannot be
      corrected with conventional lenses. CONCLUSION: The present paper demonstrates
      the application of Fourier series analysis to corneal topography data.

PMID- 9267627
TI  - Effect of human vitreous and hyalocyte-derived factors on vascular endothelial
      cell growth.
AB  - PURPOSE: In the present study we have examined the effects of human vitreous and
      hyalocyte-conditioned medium on human umbilical vein endothelial cells (HUVEC).
      METHODS: Human umbilical vein endothelial cells were cultured and treated in
      quadruplicate with human vitreous and hyalocyte-conditioned medium at different
      concentrations. Cell numbers were counted on days 1, 3, 5 and 7. Morphological
      changes and the viability of cells after treatment were also monitored. RESULTS:
      The results indicate that both human vitreous and hyalocyte-conditioned medium
      inhibit proliferation and reduce the viability of HUVEC in vitro. These
      inhibitory effects were dose- and time-dependent. CONCLUSIONS: The observations
      suggest that human hyalocytes and vitreous contain anti-angiogenic factors that
      influence vascular endothelial cell-growth. These results, combined with those of
      previous studies, may yield important information about the functional role of
      vitreous and hyalocytes in intraocular vascular regression.

PMID- 9267628
TI  - Changes in the receptive fields of cat retinal ganglion cells affected by
      pressure on the optic nerve.
AB  - In the cat optic nerve a lesion was induced by brief application of pressure. It
      selectively blocked impulse conduction in large diameter fibres of the retinal
      ganglion cells. Electrophysiological examination of single optic axons several
      weeks later demonstrated a gross alteration of the visual properties of the
      affected BT/Y ganglion cells. It is suggested that the alteration of receptive
      field properties may reflect the cellular and dendritic response to distant focal
      injury of the axon.

PMID- 9267629
TI  - Localization of D1 dopamine receptors in the chicken retina.
AB  - PURPOSE: The localization of dopamine D1 receptors (DIR) in the chicken retina
      was examined using an anti-human DIR monoclonal antibody and PAP techniques.
      RESULTS: A clear band of staining was seen in the outer plexiform layer, as well
      as cellular staining in the outer-most part of the inner nuclear layer, probably
      in a subset of horizontal cells. Many different amacrine cell bodies were
      labelled in the inner one-third of the inner nuclear layer. There was also
      extensive staining in the inner plexiform layer, which showed some striation.
      Occasional labelled ganglion cells were also detected. CONCLUSION: Localization
      of D1-dopamine receptors has been shown in the chicken retina.

PMID- 9267630
TI  - A light-driven rhythm in neurotensin-like immunoreactivity in the chicken retina.
AB  - PURPOSE: To determine if the pattern of release of neurotensin from the
      enkephalin-, neurotensin- and somatostatin-like immunoreactive amacrine cells in
      response to light and dark is the same as that of the enkephalins and
      somatostatin. METHODS/RESULTS: Both the enkephalins and somatostatin are released
      at high rates in the dark and at lower rates in the light, and these rate changes
      are reflected in increasing intracellular levels of the peptides in vivo in the
      light and decreasing levels in the dark. The levels of neurotensin-like
      immunoreactivity show a similar diurnal light-driven and non-circadian rhythm in
      vivo. CONCLUSION: This implies that the actual release rates of neurotensin
      follow the same patterns as those demonstrated in vitro for the enkephalins and
      somatostatin.

PMID- 9267631
TI  - A fundamental step-transition in retinal function at low light intensities.
AB  - There appears to be a fundamental step-transition in retinal function at low
      light intensities, close to the scotopic-mesopic transition. This step-transition
      is observed for elements of the retinal dark-light switch, which has been
      described in the chicken retina. Over the same range of light intensities, there
      is a step-transition in photoreceptor retinomotor movements and in the coupling
      of horizontal and All amacrine cells, which suggests a switch in retinal
      circuitry from rod-processing to cone-processing regimes. A similar step
      transition in pineal function suggests that the retinal step-transition signals
      to the central circadian systems. Finally, this step-transition may also inhibit
      eye growth, and thus be responsible for the reported diurnal rhythm in eye
      growth. Disturbances to this step-transition may be the initial cause of
      disordered eye growth in the form-deprivation myopia paradigm.

PMID- 9267632
TI  - Retinal control of scleral precursor synthesis.
AB  - There is a light-dependent diurnal rhythm in scleral precursor synthesis (SPS).
      In form-deprivation myopia (FDM) there is an increase in SPS. Daily periods of
      normal vision prevent FDM, but light intensities that maintain the retinal dark
      light switch in its dark state do not, implicating melatonin, dopamine,
      enkephalin, neurotensin and somatostatin in the control of SPS. FDM is also
      prevented by pirenzepine, a cholinergic muscarinic antagonist To test if these
      compounds control the rate of SPS, agonists and antagonists were applied directly
      to the sclera, but the only effects detected were at very high concentrations,
      making them physiologically insignificant.

PMID- 9267633
TI  - Dopaminergic behaviour in chicken retina and the effect of form deprivation.
AB  - PURPOSE: Dopamine (DA) is considered to be a neurotransmitter involved in light
      adaptive responses in the retina and has been implicated in the control of the
      eye growth induced by form deprivation. Vitreal DOPAC was shown to be a good
      indicator of retinal dopaminergic activity. METHODS/RESULTS: Dopaminergic
      activity was highest during the light; with vitreal DOPAC levels rising within 3
      h of light exposure. Form deprivation attenuated dopaminergic activity, as the
      rise in vitreal DOPAC levels on light exposure was reduced in form-deprived eyes,
      compared with control eyes. CONCLUSION: The lack of sustained activation of DA
      release may explain the role of DA in the control of eye-growth.

PMID- 9267634
TI  - Deprivation of form vision suppresses diurnal cycling of retinal levels of leu
      enkephalin.
AB  - Deprivation of form vision by the fitting of translucent occluders suppressed the
      diurnal cycling of enkephalinergic amacrine cells (the ENSLI amacrine cells), in
      the chicken. Daily periods of normal vision or enforcing temporal contrast using
      strobe lighting appeared to restore normal functioning of the ENSLI cells. These
      results suggest that the ENSLI cells are involved in retinal circuits that assess
      the quality of the visual image and control eye growth.

PMID- 9267635
TI  - Measurement of vasoactivity in the guinea-pig choroid.
AB  - PURPOSE: A perfusion system for studying the vasoactive properties of the guinea
      pig choroid is described. METHODS: The principle of operation is that the
      vascular resistance of the entire vascular network of an isolated, perfused eye
      can be monitored by recording the pressure required to deliver a constant flow of
      perfusate through the network. Delivery of the pharmacological agent of interest
      into the perfusate stream and the subsequent determination of the magnitude of
      any induced pressure changes allows the vasoactive potency of various agonists to
      be assessed. RESULTS: The baseline vascular resistance was 1.35 +/- 0.16 mmHg
      min/microL (mean +/- SEM; n = 10) and the mean response to intraluminal delivery
      of 124 mmol/L K+ Krebs was an increase in resistance of 297 +/- 67%. Vasoactive
      responses were sustainable for more than 8 h. CONCLUSIONS: This system will now
      be used to study the vasoactive properties of the guinea-pig choroid in greater
      detail.

PMID- 9267636
TI  - Barrier activity of fractionated human serum.
AB  - PURPOSE: Breakdown of the blood-retinal barrier is a major cause of visual loss
      in diseases such as diabetic retinopathy, age-related macular degeneration and
      retinal vein occlusion. METHODS: Human serum, fractionated by gel filtration, was
      screened for factors that enhance barrier activity by measuring electrical
      resistance across monolayers of human umbilical vein endothelial cells. RESULTS:
      Two peaks of barrier-enhancing activity were detected. The larger peak was broad,
      contained a preponderance of albumin and increased barrier activity to 183% of
      controls. The barrier-enhancing properties of the larger peak, however, appeared
      to be associated with proteins in general and not just albumin. The fractions
      associated with elution of the larger peak induced maximal increase in resistance
      in under 1 h, relative to controls. The smaller peak was associated with
      molecular weights much smaller than those of proteins.

PMID- 9267637
TI  - Absence of ganglion cell subcomponents in multifocal luminance
      electroretinograms.
AB  - Multifocal flash electroretinograms (ERG) were recorded binocularly (n = 18).
      Areas were equal or scaled with excentricity. The latter were expected to
      increase the total amplitude if ganglion cell subcomponents were involved.
      Amplitudes were intercorrelated and the factor structure was established. Scaling
      had no influence on amplitudes or on factors. Reliability and sensitivity were
      high. The second kernel first slice from the nine hexagons across the midline
      showed differences near the macula but no component increasing in latency with
      distance from the disc. Thus, multifocal flash ERG have linear spatial summation
      and no ganglion cell subcomponents.

PMID- 9267638
TI  - Correlations between observability of the spatial frequency doubled illusion and
      a multi-region pattern electroretinogram.
AB  - A glaucoma screening device based on the visibility of the spatial frequency
      doubled (FD) illusion will be marketed by Welch Allyn Ltd in the next year (ANU
      Patients (Australia) 611,585, (USA) 5,065,767 and application PL 3130). An
      underlying assumption of the method is that retinal processes are being tested.
      To test this assumption we compared the visibility of the FD illusion over a
      range of conditions and in the same spatial locations as a multi-region pattern
      electroretinogram (PERG). Grating speed and contrast were good predictors of the
      psychometric functions and PERG amplitude and phase.

PMID- 9267639
TI  - A multiple-frequency, multiple-region pattern electroretinogram investigation of
      non-linear retinal signals.
AB  - It has been proposed that the spatial frequency doubled (FD) illusion may
      originate from Y-like non-linear retinal ganglion cells. If the contrast of multi
      frequency stimuli is increased, Y cells show a phase advance in the self-sum
      frequencies but not in other output frequencies. We looked for these effects with
      a multi-region pattern electroretinogram (PERG) displaying the sum of two
      temporal frequencies in each visual field location. Regional variation was found
      in the recorded sum and difference frequencies. The results indicate that PERG
      signals become dominated by responses from Y-like cells when the FD illusion is
      seen.

PMID- 9267640
TI  - Relationship between cup-disc ratio and optic disc diameter: the Blue Mountains
      Eye Study.
AB  - PURPOSE: To determine the effects of optic disc size on vertical cup-disc ratio
      in subjects free of glaucoma and other optic nerve disease. METHODS: Data were
      collected from 3654 people, 49 years of age of older, living in the Blue
      Mountains, west of Sydney (NSW, Australia). Examinations performed included
      subjective refraction and Zeiss colour stereo optic disc photographs. Eye and
      camera magnification effects were corrected. RESULTS: Mean vertical disc diameter
      was 1.51 mm (95% confidence interval (CI) 1.504-1.516 mm) and the mean vertical
      cup-disc ratio was 0.43 (95% CI 0.425-0.435). Both parameters were distributed
      unimodally. The cup-disc ratio was strongly associated with disc diameter.
      Controlling for other variables, cup-disc ratio increased 0.270 (95% CI 0.250
      0.290) per mm increase in disc diameter. CONCLUSIONS: Vertical optic disc
      diameter and cup-disc ratio are distributed near normally in older Australians.
      Optic discs with larger vertical diameters have considerably greater vertical cup
      disc ratios.

PMID- 9267641
TI  - Lymphatic sinusoids exist in chick but not in rabbit choroid.
AB  - PURPOSE: Although it is generally thought that lymphatics do not exist in the
      choroid, there is mounting evidence that lymphatic-like structures do exist in
      primates and fowl. METHODS/RESULTS: Our comparison of the ultrastructure of chick
      and rabbit outer choroid indicates that major differences exist in the non
      vascular areas of the choroid: notably, the chick has large lymphatic sinusoids,
      whereas the rabbit only has a system of large vacuoles contained within the
      processes of individual fibroblasts. CONCLUSIONS: These results raise questions
      regarding the similarities or otherwise between species of the management of
      retinal metabolites, excess tissue fluid and choroidal homeostasis, especially
      during conditions of overload.

PMID- 9267642
TI  - Cat-301 immunoreactivity in the lateral geniculate nucleus and visual cortex of
      the strabismic amblyopic cat.
AB  - PURPOSE: It was investigated whether alterations in neuronal structure and
      function occasioned by strabismic amblyopia also may be reflected in alterations
      in the expression on Y type neurons of a Cat-301 antibody sensitive antigen in
      the lateral geniculate nucleus (LGN) and cortex of our cat model of strabismic
      amblyopia. METHODS/RESULTS: The percentage of positively labelled cells was
      reduced in LGN laminae that received input from the deviated eye in strabismic
      amblyopic cats compared with normal cats. In the strabismic cortex, the density
      of immunopositive neurons was significantly reduced compared with normal the
      effect being most pronounced in layer IV. CONCLUSIONS: Despite previous
      physiological recordings indicating a decrease in X-cell associated acuity in
      strabismic amblyopia, the present findings imply that the changes in the early
      visual experience occasioned by strabismus also produce specific molecular
      changes in the Y neuronal class.

PMID- 9267643
TI  - Development of spatial resolution, contrast sensitivity and binocularity in
      normal and strabismic kittens.

PMID- 9267644
TI  - Impaired recognition memory in patients with lesions limited to the hippocampal
      formation.
AB  - A recent literature survey of results from a widely used recognition memory test
      raised questions about the extent to which recognition memory impairment
      ordinarily occurs in human amnesia and, in particular, whether recognition memory
      is impaired at all after damage limited to the hippocampal region (J. P. Aggleton
      & C. Shaw, 1996). Experiment 1 examined the performance of 6 amnesic patients on
      11 to 25 different recognition memory tests. Three patients had bilateral lesions
      limited primarily to the hippocampus (G.D.) or the hippocampal formation (W.H.
      and L.M.), as determined by postmortem, neurohistological analysis (N. Rempel
      Clower, S. M. Zola, L. R. Squire, & D. G. Amaral, 1996). All 6 patients exhibited
      unequivocally impaired recognition memory. In Experiment 2, the 3 patients still
      available for study were each markedly impaired on a test of object recognition
      similar to the kind used to test recognition memory in nonhuman primates.
      Recognition memory impairment is a robust feature of human amnesia, even when
      damage is limited primarily to the hippocampus.

PMID- 9267645
TI  - Primacy and recency effects in rhesus monkeys (Macaca mulatta) using a serial
      probe recognition task: II. Effects of atropine sulfate.
AB  - Nonhuman primates display both a primacy and a recency effect when trained on a 6
      item serial probe recognition task. The author has previously shown that in the
      rhesus monkey, diazepam (3.2 mg/kg im) interferes with the memory processes that
      mediate the recency effect without affecting those memory processes involved in
      the primacy effect (C. A. Castro, 1995). This study assessed the effects of
      atropine sulfate (0.2, 0.3, and 0.4 mg/kg im) on the primacy and recency effects
      in these same monkeys. Opposite the effects of diazepam, atropine disrupted the
      primacy component of the serial position curve and had no measurable effect on
      the recency component. In addition, the 2 highest doses of atropine disrupted
      accuracy on the nonmatching probe trials, whereas all 3 doses of atropine
      resulted in increased response latencies. These reports indicate that the primacy
      and recency effects in the nonhuman primate can be pharmacologically dissociated.

PMID- 9267646
TI  - Functional inactivation of the lateral and basal nuclei of the amygdala by
      muscimol infusion prevents fear conditioning to an explicit conditioned stimulus
      and to contextual stimuli.
AB  - The GABAa agonist, muscimol (0.5 microgram in 0.5 microliter saline), or vehicle
      was infused into the lateral and basal amygdala nuclei prior to fear conditioning
      or testing in rats. Rats given muscimol before conditioning and saline before
      testing showed much less freezing to the conditioned stimulus (CS) and the
      context than did controls given saline before training and testing. Rats given
      saline before training and muscimol prior to testing also showed low levels of
      freezing to the CS and the context. In follow-up procedures, rats with
      acquisition initially blocked by pretraining muscimol infusions froze in a manner
      similar to that of controls when retrained and retested with saline infusions.
      Rats trained with saline but tested with muscimol presumably became conditioned
      but could express the learning. When retested with saline, they froze in the same
      manner as controls. Thus, activity in the lateral and basal amygdala appears to
      play an essential role in the acquisition and expression of fear conditioning.

PMID- 9267647
TI  - Involvement of the dorsal periaqueductal gray in the loss of fear-potentiated
      startle accompanying high footshock training.
AB  - The amplitude of acoustic startle is markedly enhanced by cues signaling
      moderately intense footshocks but, surprisingly, not by cues signaling higher
      intensity footshocks. Previous findings suggest that the ineffectiveness of high
      footshock training may involve activation of the dorsal periaqueductal gray
      (PAG). As a means of evaluating this possibility, rats trained with moderate (0.6
      mA) footshocks were later tested after intra-PAG infusion of an excitatory
      nontoxic dose of kainic acid. Kainic acid significantly reduced fear-potentiated
      startle relative to vehicle controls. In a 2nd experiment, the effect of dorsal
      PAG lesions on fear-potentiated startle to cues paired with 0.6-mA and 1.6-mA
      footshocks was evaluated. Dorsal PAG lesions prevented the disruptive effects of
      high footshock training. Together, these results suggest that dorsal PAG
      activation mediates the loss of potentiated startle accompanying high footshock
      training.

PMID- 9267648
TI  - Effect of tone-dependent fear conditioning on heart rate and behavior of C57BL/6N
      mice.
AB  - The effects of the temporal sequence of tone (conditioned stimulus [CS]) and
      footshock (unconditioned stimulus [US]) during training (acquisition) on tone
      dependent retention were studied in mice. Freezing increased significantly as an
      associative behavioral response in mice subjected to CS paired with US or after
      unpaired by 30 s in the memory test performed 24 hr after training. In the home
      cage of freely moving mice implanted with an electrocardiogram transmitter, CS
      triggered a strong tachycardiac response in the memory test. Heart rate (HR)
      increased from about 580 bpm to more than 750 bpm, and HR variability decreased
      significantly. The inhibition of the HR increase by the nonspecific beta
      adrenergic antagonist sotalol indicated the strong sympathetic contribution to
      the tachycardiac response. CS evoked a significant but minor HR increase in mice
      subjected to either CS or US only or CS and US unpaired by 60 s. Thus, HR and HR
      variability reflected associative learning.

PMID- 9267649
TI  - Normal conditioned inhibition and extinction of freezing and fear-potentiated
      startle following electrolytic lesions of medical prefrontal cortex in rats.
AB  - The authors investigated the role of medial prefrontal cortex (mPFC) in the
      inhibition of conditioned fear in rats using both Pavlovian extinction and
      conditioned inhibition paradigms. In Experiment 1, lesions of ventral mPFC did
      not interfere with conditioned inhibition of the fear-potentiated startle
      response. In Experiment 2, lesions made after acquisition of fear conditioning
      did not retard extinction of fear to a visual conditioned stimulus (CS) and did
      not impair "reinstatement" of fear after unsignaled presentations of the
      unconditioned stimulus. In Experiment 3, lesions made before fear conditioning
      did not retard extinction of fear-potentiated startle or freezing to an auditory
      CS. In both Experiments 2 and 3, extinction of fear to contextual cues was also
      unaffected by the lesions. These results indicate that ventral mPFC is not
      essential for the inhibition of fear under a variety of circumstances.

PMID- 9267650
TI  - Motor cortex lesions do not affect learning or performance of the eyeblink
      response in rabbits.
AB  - The possible modulatory role of motor cortex in classical conditioning of the
      eyeblink response was examined by ablating anterior neocortex in rabbits and
      training them with an auditory conditioned stimulus (CS) and an airpuff
      unconditioned stimulus (US) in either a delay (Experiment 1) or a trace
      (Experiment 2) conditioning paradigm. Topographic measures such as amplitude and
      onset latency were assessed during conditioning sessions for conditioned
      responses (CRs) and on separate test days for unconditioned responses (URs) by
      using a range of US intensities. No lesion effects were observed for learning or
      performance measures in acquisition or retention of either delay or trace
      conditioning. During trace conditioning, lesioned rabbits did, however, exhibit a
      trend toward impairment and demonstrated significantly longer CR latencies.
      Damage to motor and frontal cortex does not significantly affect eyeblink
      response performance or learning in either a delay or a trace conditioning
      paradigm.

PMID- 9267651
TI  - Incremental redistribution of protein kinase C underlies the acquisition curve
      during in vitro associative conditioning in Hermissenda.
AB  - An incremental increase in the excitability (i.e., input resistance, evoked spike
      frequency) of B photoreceptors in Hermissenda accompanied successive pairings of
      light and presynaptic stimulation of vestibular hair cells (simulating light
      rotation pairings in an intact animal). Analysis of protein kinase C (PKC) in the
      Hermissenda's photoreceptors indicated a training-induced incremental reduction
      of PKC in cytosolic compartments, a tendency toward an increase in membrane
      compartments, and a small decrease in total enzyme activity (possibly owing to a
      downregulation or conversion of PKC to a calcium-independent state). Neither the
      biophysical or biochemical effects were observed in Hermissenda exposed to
      unpaired light and rotation or in those trained in the presence of the selective
      PKC inhibitor NPC-15437 (which had no effect on synaptic interactions or light
      induced generator potentials). These results suggest that the intracellular
      redistribution of a protein kinase contributes critically to the kinetics of new
      learning.

PMID- 9267652
TI  - Tail-flick test: II. The role of supraspinal systems and avoidance learning.
AB  - It is held that the tail-flick test of pain depends on a spinal reflex because a
      similar response is observed in spinally transected rats. But when subjects were
      manually held and a cool heat setting was used, supraspinal systems facilitated
      the response (Experiment 1). This effect did not depend on the rate at which the
      tail was heated (Experiment 2) but rather on the co-occurrence of visual,
      auditory, and tactile cues that predict impending pain (Experiments 3 and 4).
      Subjects rapidly learned to exhibit a tail movement during these co-occurring
      cues, and this avoidance response was instrumental in nature (Experiment 5).
      Optimal learning was observed when the visual signal was presented 8-12 s before
      a heat-elicited response is normally observed (Experiment 6), and a low dose of
      morphine inhibited the performance of the instrumental response (Experiment 7).

PMID- 9267653
TI  - Cooling the area postrema induces conditioned taste aversions in male rats and
      blocks acquisition of LiCl-induced aversions.
AB  - The experiments presented in this article were designed to examine whether area
      postrema (AP) lesions attenuate LiCl-induced conditioned taste aversions (CTAs)
      by disruption of information about the illness-producing properties of LiCl or by
      a lesion-induced malaise. Reversible lesioning of the AP caused by cooling
      induced a CTA in male rats. The cooling-induced CTA could be blocked if males
      were exposed to cooling for several days before acquisition day. Acquisition of a
      LiCl-induced CTA was blocked in males if they were exposed to cooling before
      acquisition day and during LiCl administration on acquisition day was attenuated
      but not blocked in males if they were exposed to cooling only before acquisition
      day, and was unchanged in males if they were exposed to cooling only during LiCl
      administration. Taken together these results indicate that the AP is important
      for acquisition of LiCl-induced CTAs but that inactivation of this area is so
      aversive it will induce CTAs that can obscure the attenuation of LiCl-induced
      aversions.

PMID- 9267654
TI  - Executive function of the hippocampus in social behavior in the rat.
AB  - Bilateral lesion of the fimbria resulted in a reduction of social interdependency
      and agonistic behavior in male-male encounters in rats. These findings are
      hypothesized to be consistent with J. A. Gray's (1982) supervisor model, which
      assigns an executive function to the septohippocampal system. To achieve this
      interpretation, social behavior is described in terms of relational processes
      (social hypothesis, behavioral sequencing, and behavioral competition). This
      study focused mainly on the effects of the lesion on behavioral sequencing by
      studying the alterations of the predictability of the behavior of a rat in terms
      of the behavior of its partner.

PMID- 9267655
TI  - Variability in general activity and the expression of complex behavior in the
      fetal rat (Rattus norvegicus).
AB  - Rat fetuses exhibit intrinsic fluctuations in general motor activity and respond
      to an artificial nipple (AN) with mouthing and oral grasping behavior. The
      present study examined the relation between the organization of general activity
      and the expression of these specific responses to an AN on Embryonic Day 21. In
      Experiment 1, continuous exposure to the AN resulted in nonspecific behavioral
      activation characterized by an increase in amplitude and high-frequency
      variability. In Experiment 2, increased amplitude and variability in general
      activity preceding discrete presentations of the AN resulted in more mouthing and
      oral grasping responses to the AN. These results suggest that presentation of the
      AN triggers behavioral reorganization in which the level and variability of
      overall activity may facilitate expression of well-defined action patterns.

PMID- 9267656
TI  - Vernier and grating acuity in adult hooded rats: the influence of sex.
AB  - Although morphological sex differences are pervasive in the primary visual cortex
      of hooded rats, it is not known whether sex differences occur in vision in these
      rats. In this study, grating acuity was measured in a forced-choice Y maze and a
      jumping stand in adult hooded rats, and vernier acuity thresholds were
      established in the jumping stand. With a criterion of 34 correct/50 trials, the
      number of correct choices for both sexes was high (1.0-1.6 cycles per degree
      [c/deg]) for spatial gratings. Female rats made more correct identifications of
      the coarse gratings (0.125 and 0.25 c/deg) than male rats, but no sex differences
      were found for higher spatial frequencies. In contrast, male rats were better at
      detecting smaller vernier offsets in both the individual criterion and group
      averages than female rats, and all of the rats detected vernier misalignments at
      34.1 min (equivalent to 1.75 c/deg), which is above their grating acuity. Vernier
      acuity may mirror some sex differences in visual cortex anatomy.

PMID- 9267657
TI  - Relationship between auditory intensity discrimination in noise and olivocochlear
      efferent system activity in humans.
AB  - Recent physiological data in animals suggest a role of the medial olivocochlear
      system (MOCS) in auditory intensity discrimination in noise. In this study, the
      existence of statistical relationships between intensity difference limens (IDLs)
      and MOCS functioning was tested in humans. IDLs were measured in conditions of
      quiet and of ipsilateral, contralateral, and dichotic noise. MOCS functioning was
      assessed through the contralateral evoked otoacoustic emission (EOAE) amplitude
      attenuation effect. A first finding was that IDLs measured in the presence of
      ipsilateral noise were reduced when contralateral noise was added. Furthermore,
      the observed shift in IDL appeared to be significantly correlated to the
      contralateral EOAE amplitude attenuation effect. These results support the
      hypothesis that MOCS functioning plays a role in intensity discrimination in
      dichotic noise in humans.

PMID- 9267658
TI  - A kinematic analysis of sex-typical movement patterns used during evasive dodging
      to protect a food item: the role of testicular hormones.
AB  - Feeding rats dodge laterally away from a conspecific attempting to steal their
      food. Dodges by female and male rats differ in their composition of movement.
      Females pivot around a point more posterior on the longitudinal axis than do
      males, producing a greater amount of movement of the snout in relation to the
      pelvis. This experiment examined the role of testicular hormones on these sex
      typical movement patterns. Castration at weaning (21 days) does not affect the
      male-typical pattern. Neonatal testicular hormone manipulation, however, does
      alter sex-typical patterns of movements. Whereas castration neonatally makes male
      rats more female-like, injections of neonatal female rats with testosterone
      propionate make them more male-like. These findings suggest that the organization
      of sex-typical patterns of dodging involves perinatal action of gonadal hormones.
      Results are discussed in relation to anatomy, neural structure, and the role of
      gonadal hormones during development.

PMID- 9267659
TI  - Inescapable shock-induced potentiation of morphine analgesia in rats: involvement
      of opioid, GABAergic, and serotonergic mechanisms in the dorsal raphe nucleus.
AB  - Exposure of rats to inescapable shock (IS) potentiated the analgesic response to
      a low dose (1 mg/kg) of morphine 24 hr later. This effect was blocked by
      naltrexone (10 micrograms), diazepam (5 micrograms), or 8-hydroxy-2-(di-n
      propylamine)-tetralin (8-OH-DPAT; 1 microgram) microinjected into the dorsal
      raphe nucleus (DRN) 15 min before IS. When microinjected into the DRN at the time
      of tail-flick testing, 8-OH-DPAT also effectively prevented this effect. Further,
      intra-DRN administration of a beta-carboline mimicked the effects of IS, because
      rats treated with methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (1
      microgram) and simply restrained displayed potentiated morphine analgesia 24 hr
      later. These data suggest that this phenomenon shares mechanisms in common with
      other effects of IS at the level of the DRN.

PMID- 9267660
TI  - L-DOPA and quipazine elicit air-stepping in neonatal rats with spinal cord
      transections.
AB  - Acute mid-thoracic spinal cord transection eliminates hindlimb air-stepping in
      neonatal rats suspended in harnesses and administered L-DOPA. Because spinal cord
      transection eliminates all descending inputs to the hindlimb locomotor circuits,
      this experiment determined if coadministration of L-DOPA and quipazine (serotonin
      receptor agonist) would induce hindlimb air-stepping in rat pups 24 hr after
      transection. Hindlimb steps of spinally transected pups that received L-DOPA or
      quipazine alone were infrequent and slow; hindlimb steps induced by L-DOPA +
      quipazine occurred more frequently and were faster than those elicited by either
      drug alone. These findings suggest that catecholaminergic and serotonergic
      systems both contribute to hindlimb stepping.

PMID- 9267661
TI  - Fluid intake and behavioral changes in rats associated with the distension of the
      small and large intestine.
AB  - Effects of volumetric distension of the small and the large intestine on rats'
      behavior were compared. Rats were stimulated by a rubber balloon inserted into
      chronic isolated intestinal loops prepared from the lower duodenum-upper jejunum
      and from the upper colon in the same animal. Thresholds of 3 reaction classes
      (weak, strong, and painful) were not different from each other in the 2 loops.
      Distension decreased fluid intake in an intensity-dependent way, with weak and
      painful stimuli being less effective in the large intestine and strong stimuli
      less effective in the small bowel. Behavioral indexes supported intake data,
      satiety indexes were similar to each other and changed in time, whereas
      aversivity indexes differed in the 2 loops and as a function of intensity but not
      time. The author suggests that mild discomfort is a physiological satiety factor
      whereas strong and painful stimuli signal danger and induce aversivity.

PMID- 9267663
TI  - Intact perceptual memory in the absence of conscious memory.
AB  - Declarative memory enables conscious recollection of the past and has been
      proposed to be distinct from priming, a perceptual form of memory that operates
      nonconsciously and improves the ability to detect or identify recently presented
      stimuli. Yet, it has been difficult to obtain unambiguous evidence for the
      independence of declarative memory and priming. The authors report the first
      demonstration, using matched tests, of fully intact perceptual memory (priming)
      in a profoundly amnesic patient (E.P.), despite at-chance recognition memory. The
      priming and recognition tests included tests that were matched with respect to
      test materials, length of the study and test lists, and the kind of cues
      available at test. Priming appears to reflect neural changes within perceptual
      processing systems that occur before information reaches the brain systems that
      transform visual perception into conscious visual memory.

PMID- 9267662
TI  - A large sex difference on a two-dimensional mental rotation task.
AB  - Mental rotation tests require participants to identify rotated versions of a
      target stimulus. The Vandenberg Mental Rotations Test depicts rotations in 3-D
      space and typically yields one of the largest established cognitive sex
      differences favoring males. It is presently unclear whether this male advantage
      is related to the nature of rotations depicted in 3-D space or to the high level
      of difficulty of this task. The present study developed a new test depicting
      picture plane, or 2-D, rotations. When task difficulty within this 2-D test was
      varied, a male advantage as large as that seen on the Vandenberg test was found
      for the difficult component. These findings suggest that processing in 3
      dimensions is not a necessary condition for a large sex difference on tests of
      mental rotation.

PMID- 9267664
TI  - Fear-potentiated startle in two strains of inbred mice.
AB  - The fear-potentiated startle paradigm has been used with great success to examine
      conditioned fear in both rats and humans. The purpose of this study was to
      examine fear-potentiated startle in inbred mice. One-month-old C57BL/6J (C57) and
      DBA/2J (DBA) mice were given tone + foot shock training trials. The amplitude of
      the acoustic startle reflex was measured in the presence and absence of the tone
      both before and after training. Both strains showed fear-potentiated startle
      after training as evidenced by larger startle amplitudes in the presence of the
      tone than in its absence. However, the magnitude of fear-potentiated startle was
      greater in DBA mice than in C57 mice. These results not only demonstrate fear
      potentiated startle in mice for the first time but also suggest that fear
      potentiated startle can be influenced by characteristics of the mouse strain.

PMID- 9267665
TI  - Inter-strain graft-vs.-host disease T-cell responses to immunodominant minor
      histocompatibility antigens.
AB  - Immunodominance affects the in vitro generation of cytotoxic T lymphocytes (CTL)
      specific for minor histocompatibility antigens (miHA), as exemplified in the
      C57BL/6By (B6) anti-BALB.B H2b-matched strain combination. Despite the potential
      of responding to numerous individual miHA on BALB.B antigen presenting cells, the
      focus of the CTL response is largely directed to only a limited number of target
      antigens. These miHA are differentially expressed by the CXBE, CXBG, CXBI, CXBJ,
      and CXBK recombinant inbred (RI) strains, all of which also express the H2b MHC
      haplotype. Immunodominance also plays a role in the development of lethal graft
      vs.-host disease (GVHD) directed to miHA, by which B6 T cells were transplanted
      along with T-cell depleted bone marrow to irradiated (825 cGy) recipients of
      either the BALB.B or CXB RI strains. The hierarchy of immunodominance differed in
      GVHD from that predicted from the in vitro CTL studies; i.e., GVHD was observed
      in BALB.B, CXBE, CXBI, and CXBJ recipients, but not in CXBG and CXBK recipients,
      despite the latter two strains expressing immunodominant antigens for CTL
      generation. Interpretation of these results was complicated by the finding that
      potent GVHD could be obtained with the transfer of CXBE T cells and ATBM to
      irradiated CXBG recipients. To clarify the scope of the inter-strain
      immunodominant interactions involved in GVHD in these strain combinations and to
      estimate the minimum number of miHA that could be responsible for GVHD, a full
      panel of GVHD responses was analyzed. The GVHD potential was evaluated for donor
      T cells derived from both parental RI strains as well as for (B6 x RI)F1 hybrids
      to restrict responses to only those miHA originating from BALB.B origin. The
      results were consistent with the minimal involvement of two distinct
      immunodominant miHA in the B6-->BALB.B lethal GVHD response. One immunodominant
      miHA (GVH-1) appeared to be shared by the CXBE, CXBI, and CXBJ RI strains, while
      the second antigen (GVH-2) was uniquely expressed by the parental BALB.B strain.

PMID- 9267666
TI  - Immune reconstitution following T-cell depleted bone marrow transplantation:
      effect of age and posttransplant graft rejection prophylaxis.
AB  - Transplantation of T-cell depleted bone marrow has been associated with an
      increased risk of graft failure, requiring additional immunosuppression to
      prevent this complication. To determine the effect of graft rejection prophylaxis
      with posttransplant anti-thymocyte globulin and methylprednisolone on immune
      reconstitution, the lymphoid phenotype, function, and infectious complications of
      170 recipients of a T-cell depleted bone marrow transplantation, 57 of whom
      received prophylaxis, were analyzed. Neutrophil recovery and normalization of T
      cell numbers were more rapid in patients given anti-thymocyte globulin and
      methylprednisolone. Adults given graft rejection prophylaxis had prolonged
      inversion of their CD4/CD8 ratio, increased numbers of CD8+ CD11b+, HLA-DR+,
      CD57+, CD28- T cells, and delayed recovery of T-cell mitogen responses when
      compared to adults not given ATG and steroids. Even without posttransplant
      immunosuppression to prevent graft failure, adults experienced delayed recovery
      of total and CD45RA+ CD4+ cells, prolonged inversion of the CD4/CD8 ratio, and
      delayed recovery of T-cell mitogen responses when compared to children. During
      the first posttransplant year, Epstein-Barr Virus-Associated Lymphoproliferative
      disorders and opportunistic infections were increased in patients given
      prophylaxis. Patients who developed an opportunistic infection or EBV-LPD had
      significantly fewer circulating CD4+ T cells than those who did not. This study
      demonstrates that older age and graft rejection prophylaxis, rather than T-cell
      depletion alone, are associated with delayed immune reconstitution. In addition,
      it suggests that CD4 cell counts may be useful in predicting which patients are
      at increased risk of developing opportunistic infections following successful
      engraftment.

PMID- 9267667
TI  - The impact of T-cell depletion on the effects of HLA DR beta 1 and DQ beta allele
      matching in HLA serologically identical unrelated donor bone marrow
      transplantation.
AB  - Unrelated donor bone marrow transplants have been associated with relatively high
      rates of acute graft-vs.-host disease and treatment-related mortality. These
      complications reflect histo-incompatibility between donor and recipient.
      Molecular technology has recently been applied to HLA typing to identify alleles
      not distinguishable with serologic typing techniques. We report results in 92
      unrelated marrow transplant recipients who were HLA seroidentical with donor HLA
      A, -B, and -DR antigens and assess the effect of DR beta 1 and DQ beta
      compatibility using sequence specific oligonucleotide primers. Forty-eight
      patients received T-cell depleted marrow grafts, and 44 received unmodified
      grafts. Among recipients of unmodified marrow grafts, matching for both DR beta 1
      and DQ beta reduced the rate of grade 3-4 acute graft-vs.-host disease to 38 +/-
      20% vs. 73 +/- 20% among recipients mismatched for either allele (p = 0.02). This
      difference was not observed in recipients of T-cell depleted marrow grafts.
      Multivariate analysis confirmed matching for both DR beta 1 and DQ beta loci (p =
      0.015), and receiving a T-cell depleted graft (p = 0.008) independently predicted
      for reduced risk of grade 3-4 acute graft-vs.-host disease. In conclusion, both
      DR beta 1 and DQ beta appear biologically important for development of acute
      graft-vs.-host disease in patients receiving unmanipulated marrow grafts for
      unrelated donor transplant.

PMID- 9267668
TI  - Collection of peripheral blood stem cells following administration of paclitaxel,
      cyclophosphamide, and filgrastim in patients with breast and ovarian cancer.
AB  - PURPOSE: To determine the toxicities and efficacy of paclitaxel, cyclophosphamide
      (Cy), and recombinant human granulocyte-colony stimulating factor (filgrastim)
      administered for mobilization and collection of peripheral blood stem cells
      (PBSC) in patients with breast and ovarian cancer. METHODS: One hundred and forty
      one patients with breast (n = 115) or ovarian cancer (n = 26) received paclitaxel
      170 mg/m2 and Cy 2 gm/m2 (n = 42) or paclitaxel 200 mg/m2, Cy 3 gm/m2 (n = 99),
      and filgrastim (6 micrograms/kg/day) followed by collection of PBSC by apheresis.
      RESULTS: The 2 dose levels of paclitaxel and Cy tested were well tolerated. The
      median yield of CD34+ cells from all patients was 6.53 x 10(6)/kg (range, 0.11
      51.76) collected with a median of 2 aphereses (range, 1-8). The target dose of
      2.5 x 10(6) CD34+ cells/kg was achieved in 85% of patients. The mean daily
      collection of CD34+ cells was 5.46 x 10(6)/kg for patients receiving 200 mg/m2 of
      paclitaxel and 3 gm/m2 of Cy as compared to 2.77 for patients receiving the lower
      doses (p = 0.0005). Increasing the dose of paclitaxel and Cy did not
      significantly increase the fraction of patients achieving a target dose of 2.5 x
      10(6) CD34+ cells/kg (87% vs 81%, p = 0.367) but did increase the fraction
      achieving a target of 5.0 x 10(6) CD34+ cells/kg (73% vs 45%, p = 0.002). The
      mean daily collection of CD34+ cells for patients who had received only 1 prior
      chemotherapy regimen was 6.59 x 10(6)/kg as compared to 3.47 for patients who had
      received more than 1 prior chemotherapy regimen (p < 0.0001). Prior radiation
      therapy (p = 0.003) and patient performance status (p = 0.047) were adverse risk
      factors for achieving a target dose of > or = 2.5 x 10(6) CD34+ cells/kg.
      CONCLUSIONS: The combination of paclitaxel, Cy, and filgrastim can be
      administered with acceptable toxicity, allowing collection of adequate quantities
      of PBSC from the majority of patients with breast and ovarian cancer. Increasing
      the doses of paclitaxel and Cy increased the number of CD34+ cells collected and
      decreased the number of apheresis procedures necessary to collect target cell
      doses. However, increasing drug doses did not increase the fraction of patients
      yielding the minimum CD34+ target dose of 2.5 x 10(6)/kg. Collection of PBSC
      early in the disease course is the best strategy to assure optimal CD34+ cell
      doses in all patients.

PMID- 9267669
TI  - The significance of tumor contamination in the bone marrow from high-risk primary
      breast cancer patients treated with high-dose chemotherapy and hematopoietic
      support.
AB  - We studied the incidence and significance of tumor cell contamination of the bone
      marrow or peripheral blood progenitor cells of patients who had high risk primary
      breast cancer involving 10 or more axillary lymph nodes and who received high
      dose cyclophosphamide, cisplatin, and carmustine with hematopoietic support as
      consolidation following standard dose adjuvant chemotherapy. The autologous
      hematopoietic cell products were evaluated in 85 eligible patients. Eighty-three
      samples were available from the time of bone marrow harvest, and peripheral blood
      progenitor cells were evaluated from 57 of the 65 patients who additionally
      received these products. The screening technique utilized a panel of four anti
      breast cancer monoclonal antibodies and an immunohistochemical technique. Thirty
      (36%) of the 83 evaluable patients had tumor cell contamination of the bone
      marrow. Only 2 (4%) of the 57 patients had tumor cell contamination of the
      peripheral blood progenitor cells. Tumor cell contamination of the bone marrow
      was associated with shorter disease-free survival and overall survival. In
      addition, the higher the number of tumor cells identified, the shorter disease
      free and overall survival. There was no relationship between the tumor cell
      contamination of the bone marrow and the site of relapse. The combination of the
      log of the number of tumor cells +1 and number of positive lymph nodes predicted
      both disease-free and overall survival. Tumor cell contamination of the bone
      marrow from the harvest is associated with shorter disease-free and overall
      survival for patients who were treated with standard dose chemotherapy followed
      by consolidation with high dose alkylating agents and hematopoietic support. It
      is unclear what role the contaminating tumor cells have in relapse, and they may
      just be a high-risk marker. A comparison with other prognostic factors and
      characteristics of the tumor may determine the significance of the tumor
      contamination of the bone marrow.

PMID- 9267671
TI  - What risk of inducing GVHD is associated with allogeneic grafts of PBPC as
      compared to bone marrow?

PMID- 9267672
TI  - Human meconium has potent antioxidative properties.
AB  - In vitro the antioxidative capacity of pooled and lyophilized human meconium,
      measured by chemiluminescence, was compared to that of three potent antioxidants:
      vitamin C, a vitamin E analogue and a synthetic antioxidant, butylated
      hydroxytoluene. Meconium showed a significant superoxide trapping and
      peroxidation prevention capacity, but its capacity to trap peroxyl radicals was
      minor. These effects of meconium were possibly due to bilirubin and ubiquinol-10,
      both found in high concentrations in meconium. It is speculated that human
      meconium may have a physiological role as an important endogenous antioxidant
      during perinatal transition.

PMID- 9267670
TI  - High-dose cyclophosphamide, carmustine, and etoposide with autologous
      transplantation in Hodgkin's disease: a prognostic model for treatment outcomes.
AB  - PURPOSE: To identify clinical factors predictive of treatment outcome after high
      dose chemotherapy (HDC) for Hodgkin's disease and to develop a prognostic model
      for progression-free and overall survival. PATIENTS AND METHODS: 102 patients
      with relapsed or refractory Hodgkin's disease were treated with high-dose
      cyclophosphamide, carmustine, and etoposide and autologous marrow and/or
      peripheral blood progenitor cell support. Median follow-up of survivors is 4.1
      years (1.8-7.5 years). Factors potentially important for treatment outcome were
      examined in univariate analysis, and Cox regression with forward selection was
      performed. A prognostic model was developed. RESULTS: Poorer progression-free and
      overall survival were associated with nodular sclerosis histology, abnormal
      performance status, progressive disease at HDC, more than one extranodal site of
      disease, and shorter time from initial diagnosis to HDC. These factors and the
      presence of B symptoms at relapse also predicted for decreased overall survival.
      Progressive disease immediately prior to HDC, more than one extranodal disease
      site, and abnormal performance status retained significance for both progression
      free and overall survival in multivariate analysis. Progression-free and overall
      survival are 42% (95% confidence interval, CI, 34 to 53) and 65% (95% CI 54 to
      73) at three years. A model based on number of risk factors present divides
      patients into low, intermediate, and high risk groups with three-year actuarial
      survival of 82%, 56%, and 19% respectively. Treatment outcome for patients
      treated with HDC at first chemotherapy relapse was not significantly different
      from that of the group overall (p > 0.3). CONCLUSIONS: Asymptomatic patients with
      Hodgkin's disease involving at most one extranodal site whose disease is
      controlled by conventional dose chemotherapy or radiation therapy at the time of
      HDC have good outcomes after this therapy. Presence of increasing numbers of risk
      factors are associated with poorer outcomes. Results of HDC compare favorably to
      those of standard dose salvage therapy. These data can be used to estimate likely
      outcomes in patients undergoing HDC for Hodgkin's disease, to identify potential
      candidates for innovative therapies, and to evaluate strategies for the optimal
      use of HDC in Hodgkin's disease.

PMID- 9267674
TI  - Maternal, placental and cord zinc components in healthy women with different
      levels of serum zinc.
AB  - Serum zinc is known to decrease during pregnancy, but the range of individual
      values at the end of normal gestation may be considerably large, with uncertain
      physiological significance in terms of maternal zinc status and maternal-fetal
      transfer of zinc. In this study we compared several maternal and cord blood
      indices of zinc status, placental zinc, placental metallothionein and the
      relationship between maternal, cord and placental components, in 40 healthy
      pregnant women at delivery with different levels of serum zinc. Subjects were
      divided into three groups according to serum zinc using as cutoff points the
      lower and upper quartile values [LZn, < 7.6 mumol/l (n = 10); MZn, 7.6-10.7
      mumol/l (n = 20), and HZn, > 10.7 mumol/l (n = 10)]. Habitual zinc intakes were
      similar in all groups (average 11.5 mg/day). Considering all women, maternal
      serum and erythrocyte zinc correlated significantly (r = 0.40; p = 0.021).
      Maternal erythrocyte zinc was higher (p < 0.01) in HZn compared to the other
      groups. Maternal and cord values of serum zinc correlated significantly (r =
      0.43; p = 0.006). Cord serum zinc values were very similar in LZn and MZn but
      were higher (p < 0.01) in HZn. Cord erythrocyte zinc levels were similar in all
      groups and about 20-25% of the maternal values. Cord erythrocyte metallothionein
      levels were also similar in all groups and similar to maternal values. Comparing
      the percentage distribution of zinc in maternal and cord serum fractions, major
      differences were observed in HZn, with zinc in albumin fraction being 70% in cord
      compared to 56% in maternal serum. There was a higher (p < 0.01) percentage of
      zinc bound to alpha 2-macroglobulin fraction in maternal serum of HZn compared to
      maternal serum of the other groups. Maternal and cord zinc in the albumin
      fractions correlated significantly (r = 0.48; p = 0.002) particularly in HZn (r =
      0.71; p < 0.021). Placental zinc correlated negatively (r = -0.34; p = 0.035)
      with zinc in the maternal alpha 2-macroglobulin fraction, but did not relate to
      placental metallothionein, which had similar levels in all groups (average 0.28
      nmol/g wet tissue). Placental zinc levels were lower (p < 0.01) in HZn. Our
      results indicate that high levels of maternal serum zinc in healthy women at
      delivery may be related to maternal tissue zinc redistribution that could favor
      diffusional components of maternal-fetal transfer of zinc.

PMID- 9267673
TI  - Antithrombin-III substitution in preterm infants--effect on intracranial
      hemorrhage and coagulation parameters.
AB  - In preterm infants the activity of antithrombin III (AT-III), the main inhibitor
      of thrombin, is reduced depending on gestational age and complications such as
      sepsis or respiratory distress syndrome. Babies with low levels of AT-III have
      been shown to have a higher mortality and an increased incidence of intracranial
      hemorrhage. In our study we tried to show the effect of early AT-III substitution
      on coagulation parameters and the incidence of intraventricular hemorrhage (IVH).
      One hundred three preterm infants at a gestational age of 25-32 weeks (mean 28.9
      weeks; birth weight 600-2,170 g, mean 1,285 g) received AT-III concentrate at a
      single dosage of 50-200 IU/kg on the day of birth and subsequently only in case
      of a new decrease below an AT-III activity of 50%. We measured AT-III activity,
      Quick's prothrombin time (PT), partial thromboplastin time (PTT) and platelet
      count on the day of birth, and after 1 and 5-9 days in 25 patients. AT-III
      activity before substitution was lower than described for term infants (20-72%,
      mean 40%). Within the first week of life Quick's PT and PTT reached almost term
      values. No significant differences of the platelet count were found within the
      first week of life. The incidence of IVH was lower than in current epidemiologic
      studies: in only 13% of the study patients. Six percent of the infants had IVH
      grade I, 3% grade II, 4% grade III and none grade IV. Therefore, in preterm
      infants AT-III substitution may reduce the incidence and progression of
      intracranial hemorrhage.

PMID- 9267675
TI  - Heart rate biorhythm changes during the first three months of life.
AB  - Heart rate (HR) was recorded in healthy full-term newborns aged 1-90 days. The
      aim of this study was to study the existence of circadian and/or ultradian
      rhythms in HR to determine maturity. HR was recorded during 24 h, at 30-min
      intervals, at different postnatal ages. Six-groups were investigated: day 1
      (group 1); day 7 (group 7); day 15 (group 15); day 30 (group 30); day 60 (group
      60), and day 90 (group 90). The chronograms for HR showed peaks and nadirs along
      the 24-hour periods, and the cosinor analysis proved the existence of 3-hour
      ultradian rhythm in groups 1, 7 and 30, and a 12-hour ultradian rhythm in group
      90 (p < 0.01 in all cases). The same type of analysis confirmed the existence of
      a circadian rhythm in group 30. Similar results were obtained for groups 60 and
      90 (p < 0.05). IN CONCLUSION: at birth, newborns have an endogenous ultradian
      period of 3 h. A circadian rhythm appears within 15-30 days of postnatal life.

PMID- 9267676
TI  - Possible role of uric acid as an antioxidant in premature infants.
AB  - Uric acid (UA) is a water-soluble antioxidant in human body fluids. In umbilical
      cord blood of 172 neonates with gestational ages between 22 and 42 weeks, UA
      concentrations were between 50 and 990 mumol/l. There was no correlation with
      gestational age. Infants with an umbilical cord pH < 7.0 had markedly lower UA
      concentrations in cord blood than neonates without severe acidosis. UA levels
      increased during the first 24 h of life and subsequently declined within 2 weeks
      to lower levels than in older children. In tracheal aspirates (TA), UA at
      concentrations of about 10(-4) mol/l was found capable of effectively scavenging
      free oxygen radicals. Luminol-dependent chemiluminescence activity of isolated TA
      phagocytes or alveolar macrophages was suppressed by UA dose dependently, with a
      100% reduction at UA concentrations of 10(-3) mol/l. On the assumption that
      oxidative stress contributes to the development of chronic lung disease (CLD), in
      premature infants the ratio of the antioxidant UA and malondialdehyde (MDA) as a
      marker of oxidative injury was measured in serially obtained TA of 102 ventilated
      premature infants with birth weights < 1,500 g. At the age of 3-14 days, infants
      who later developed severe CLD had significantly lower TA UA/MDA ratios than
      infants without CLD development. In infants with moderate CLD, UA/MDA ratios were
      comparable to those in the non-CLD group until day 5. During the next 2 weeks,
      decreasing ratios of UA/MDA paralleled lung injury with increased oxygen
      requirement and microvascular permeability. Serum UA concentrations did not
      differ between groups. It is speculated that UA may be physiologically important
      as an antioxidant in the epithelial lining fluid of the respiratory tract in
      neonates during the 1st week of life.

PMID- 9267678
TI  - Effect of hypoxia on amniotic fluid erythropoietin levels in fetal rats.
AB  - Erythropoietin (EPO) levels in amniotic fluid and serum were measured in hypoxic
      (fraction of inspired oxygen, FiO2, 0.09) and posthypoxic (following a 24-hour
      period of hypoxia, FiO2 0.09) fetal rats on day 21 of gestation. Each of the
      study groups comprised 12-20 fetuses. Each of the control groups consisted of 21
      or 22 fetuses. Fetal serum EPO levels at 3, 6, 9, 12, and 24 h of hypoxia were
      significantly higher than the control level. Amniotic fluid EPO levels at 9, 12,
      and 24 h of hypoxia were also significantly increased compared to the control
      level. Fetal serum EPO levels returned to baseline during the 12- to 48-hour
      period after hypoxia. During the 0- to 48-hour posthypoxic period, amniotic fluid
      EPO levels were significantly higher than the control level. These data
      demonstrate that rates of appearance and turnover of amniotic fluid EPO are
      different from those of fetal serum EPO.

PMID- 9267677
TI  - Effects of timing, dosage, and duration of morphine intake during pregnancy on
      the amount of morphine in meconium in a rat model.
AB  - Meconium drug analysis is a new and sensitive test for detecting the intrauterine
      exposure of infants to drugs of abuse. To explore other potential, diagnostic use
      of the test, we studied, in timed pregnant rats, the relationship between timing,
      dosage, and duration of morphine administration to the dam and the concentration
      of morphine, analyzed by radioimmunoassay, in their pups' meconium. The term
      'meconium' refers to both the intestine and its contents. Due to the minute size
      of the pups' intestines, the intestinal contents were not separated from the
      intestines. The mean morphine concentration in meconium was found to be
      significantly (p < 0.05) higher in the groups treated with a higher morphine dose
      (10 vs. 5 mg/ kg/day), longer duration of treatment (7-20 vs. 18-20 days), or
      treated during the last week of gestation (14-20 vs. 1-6 or 7-13 days). We
      conclude that the concentration of a drug in the meconium is related to amount,
      timing, or duration of the drug exposure of the fetus, in utero. The quantitative
      analysis of drugs in the meconium, therefore, provides added information which
      enhances the diagnostic use of the test.

PMID- 9267679
TI  - The adrenal secretion of catecholamines during systemic metabolic acidosis in
      fetal sheep.
AB  - This study was undertaken to determine whether or not metabolic acidemia per se
      stimulates catecholamine (CA) secretion from the adrenal medulla in fetal sheep.
      The potential confounding effect of low O2 content, occasioned by the right shift
      in the oxyhemoglobin dissociation curve with acidemia, was taken into account in
      experimental design. Hemodynamic values, blood gases, O2 content, lactate and
      glucose concentrations and adrenal CA secretion rates and plasma CA levels were
      studied in fetal sheep at baseline and during control (saline infusion) and
      acidemic (15 and 30% lactic acid infusion) periods. Experiments were conducted
      after recovery from preparative operations performed under general anesthesia.
      Arterial pH did not change with saline infusion. During 15 and 30% lactic acid
      infusions, pH fell to 7.23 and 7.09, respectively, as lactate concentrations
      increased 4.7 and 10 times. Arterial PCO2 increased from 50 to 58 torr during 30%
      lactic acid infusion. Fetal CA secretion and plasma concentrations did not change
      during saline, or 15 or 30% lactic acid infusions. Moreover, hemodynamic
      parameters did not indicate increased CA secretion. In conclusion, we found no
      evidence for stimulation of adrenal CA secretion by metabolic acidosis.

PMID- 9267680
TI  - Prediction of absolute bioavailability for drugs using oral and renal clearance
      following a single oral dose: a critical view.
AB  - In order to determine the absolute bioavailability, both oral and intravenous
      administrations of a drug are often used. Recently a new method has been proposed
      to determine absolute bioavailability in the absence of intravenous dose.
      Following a single oral dose, this method requires oral and renal clearance data
      from normal subjects and renal failure patients. The bioavailability is
      calculated from a plot of oral against renal clearance following an oral dose,
      where the inverse of the slope is equal to absolute bioavailability. This study
      examines the prediction of absolute bioavailability from the proposed method for
      eight drugs which have a wide range of oral and renal clearance. From this study,
      it appears that the proposed method may not be reliable for the prediction of
      absolute bioavailability and further investigation is needed to test the validity
      of this method.

PMID- 9267681
TI  - DeMonS--a new deconvolution method for estimating drug absorbed at different time
      intervals and/or drug disposition model parameters using a monotonic cubic
      spline.
AB  - DeMonS-a new numerical deconvolution method for estimating the amount of drug
      absorbed at different time intervals and/or drug disposition model parameters-is
      presented here. In DeMonS, the amount of drug absorbed at different time
      intervals and/or drug disposition model parameters are the unknown parameters to
      be calculated. The Fritsch-Butland non-decreasing cubic spline was constructed
      from the cumulative amount of drug absorbed-time data directly derived from the
      calculated amount of drug absorbed at different time intervals. The drug
      absorption rate, which is the derivative of this non-decreasing cubic spline, is
      therefore represented by a piecewise non-negative quadratic function. The drug
      concentrations were obtained by convoluting the drug absorption rate quadratic
      function with the drug disposition model function. The nonlinear optimization
      method with simple parameter bounds was used to estimate the optimal set of
      unknown parameters by minimizing the sum of squares of residuals between the
      observed and predicted drug concentrations. DeMonS has been applied to (i) the
      griseofulvin data for estimating drug absorbed at different time intervals when
      the drug disposition model parameters were determined separately from intravenous
      data, (ii) veralipride double-peak phenomenon data to estimate simultaneously the
      percentage of cumulative veralipride absorbed and the veralipride disposition
      model parameters without reference intravenous data, (iii) a comparative
      bioequivalence study of gastrointestinal therapeutic system (GITS)
      pseudoephedrine HCI (PeHCI) controlled-release oral dosage forms when the drug
      disposition model parameters were not available, and (iv) estimation of both drug
      disposition model parameters and the absorption rate of drug from Testoderm
      (testosterone transdermal system) in the presence of endogenous testosterone
      production. DeMonS was implemented using MATLAB and NAG MATLAB Toolbox, and is
      available for Windows 3.1.

PMID- 9267682
TI  - Comparative bioavailability of letrozole under fed and fasting conditions in 12
      healthy subjects after a 2.5 mg single oral administration.
AB  - Letrozole is a new non-steroidal inhibitor of the aromatase enzyme system. It is
      currently under development for the treatment of postmenopausal women with
      advanced breast cancer. To investigate the influence of food on the
      bioavailability of letrozole, 12 healthy male volunteers were treated under fed
      and fasted conditions with single oral doses of 2.5 mg letrozole in film-coated
      tablets. Plasma concentration profiles were determined. No significant difference
      in the extent of absorption (AUC or AUC0-8 h) was observed between the two
      treatments but the rate of letrozole absorption decreased slightly under fed
      conditions. However, in view of the half-life of about 2 d this small change in
      the absorption rate is not considered to be of clinical relevance for treatment
      with repeated administrations.

PMID- 9267683
TI  - Extrahepatic first-pass metabolism of nifedipine in the rat.
AB  - The peroral (p.o.) bioavailability of nifedipine is reported to range from about
      45 to 58% in the rat; this compares favourably to human beings. The metabolism of
      nifedipine is similar in rats and humans (oxidation of the dihydropyridine ring),
      with the liver believed to be solely responsible for the systemic clearance of
      the drug and the observed first-pass effect after p.o. dosing. The purpose of
      this study was to determine whether intestinal metabolism also contributes to the
      first-pass elimination of nifedipine in the rat. The systemic availabilities of
      nifedipine doses given by po, intracolonic (i.c.), and intraperitoneal (i.p.)
      routes of administration were compared to that for an intravenous (i.v.) dose (in
      each case a dose of 6 mg kg-1 was given) using adult male Sprague-Dawley rats
      (249-311 g, n = 6 or 7/group). The geometric mean of systemic nifedipine plasma
      clearance after i.v. dosing was 10.3 mL min-1 kg-1. The nifedipine blood-to
      plasma ratio was found to be about 0.59. Therefore, the systemic blood clearance
      of nifedipine was about 17.5 mL min-1 kg-1; which, compared to the hepatic blood
      flow of rats (55 to 80 mL min-1 kg-1) showed that nifedipine is poorly extracted
      by the liver (0.22 < or = EH < = 0.32). The mean absolute bioavailabilities of
      the p.o., i.p., and i.c. doses were 61, 90, and 100%, respectively. Assuming
      complete absorption of the extravascular nifedipine doses these results indicate
      that, in addition to hepatic extraction, substantial first-pass elimination of
      nifedipine occurs within the wall of the small intestine but not the colon of the
      rat.

PMID- 9267684
TI  - Intestinal absorption kinetics of amiodarone in rat small intestine.
AB  - Amiodarone is a widely used antiarrhythmic agent with highly variable therapeutic
      effects. These seem to be related, at least in part, to the pharmacokinetics of
      the drug and particularly to some features of its gastrointestinal absorption
      process. The drug exhibits physico-chemical properties highly suitable for
      diffusion across lipophilic absorbing membranes, but its low aqueous solubility
      can act as the rate limiting step for absorption, making the process erratic and
      variable. In order to gain an insight into the intestinal absorption mechanism of
      the drug and detect possible non-linearities, a series of experiments using a
      classical rat gut in situ preparation were carried out with three amiodarone
      hydrochloride solutions (10, 75, and 200 micrograms mL-1). A synthetic non-ionic
      surfactant, polysorbate 80, at supramicellar concentration (2 mM) was used as the
      drug solubilizer. Amiodarone was assayed in biological samples by HPLC using a
      rapid, sensitive technique that was validated. The amiodarone first-order
      absorption rate constants obtained in these conditions were similar. No
      significant differences between ka values were found. Amiodarone absorption was
      clearly identified as a passive diffusion process.

PMID- 9267685
TI  - Effects of food, antacid, and dosage form on the pharmacokinetics and relative
      bioavailability of sertindole in healthy volunteers.
AB  - The pharmacokinetic disposition and relative bioavailability of sertindole
      administered as a tablet dosage form under fasting conditions, in the presence of
      food, in the presence of antacid, and as solution was studied in a four-way
      crossover in young healthy male volunteers. Overall, tablet dosing after a meal
      or Maalox had no effect on t1/2 or AUC values when compared to fasting
      conditions, but increased the tmax and decreased the Cmax values slightly. The
      mean relative bioavailabilities of sertindole administered as tablets after
      fasting, with food, and with Maalox are 99, 104, and 98%, respectively, compared
      to sertindole solution. Therefore, sertindole can be administered with and
      without food and without regard to coadministration of antacids.

PMID- 9267686
TI  - Pharmacokinetics and multiple peaking of acebutolol enantiomers in rats.
AB  - Acebutolol (AC) is a chiral beta-blocker which is extensively metabolized to an
      active, chiral metabolite, diacetolol (DC). Similar to some other beta
      adrenoceptors, AC exhibits multiple peaks in plasma concentration-time curves
      after oral doses to humans. We examined the suitability of the rat as an animal
      model and studied the effect of various factors including the route of
      administration, food, and bile on the pharmacokinetics of AC enantiomers.
      Pharmacokinetics of AC were delineated after oral (fed and fasted), i.v., and
      i.p. doses, and after oral and i.v. doses, to intact and bile-duct-ligated female
      Sprague-Dawley rats, respectively. The possibility of intestinal metabolism or
      saturable absorption was studied in vitro using everted rat gut. Multiple peaks
      were present but only after oral doses independent of food intake, suggestive of
      gastrointestinal tract involvement. Oral absorption of AC enantiomers was
      incomplete as bioavailability was lower after oral (R, 0.59; S, 0.63) as compared
      to i.p. off(R, 0.86; S, 0.84) doses. Food reduced bioavailability by 60%. A 250
      fold increase in the dose did not alter the absorption kinetics of AC through the
      everted gut, ruling out the possibility of saturable absorption. No intestinal
      metabolism was detected in vitro. Enterohepatic recirculation cannot be
      responsible as ligation of the bile duct did not alter the pattern or route
      dependence of the multiple peaking. The rat appears to be a suitable animal
      model; a bile- and food-independent erratic absorption is probably responsible
      for the observed multiple peaking of AC.

PMID- 9267688
TI  - The expression of thyroid hormone receptors in human bone.
AB  - The mechanism of action of thyroid hormones on bone is poorly understood. Thyroid
      hormones may act on bone cells either indirectly by increasing secretion of
      growth hormone (GH) and insulin-like growth factor-1 (IGF-1), or directly by
      influencing target genes via specific nuclear receptors. The presence of thyroid
      hormone receptors (TRs) has been demonstrated in human and rodent osteoblast-like
      cells and cell lines and recently in osteoclasts derived from an osteoclastoma in
      vitro. However, their presence in human bone in situ has not been reported. We
      have used specific polyclonal antibodies to TR-alpha 1, -alpha 2, and -beta 1 to
      investigate the expression of these receptors in sections of human osteophytes
      and heterotopic bone. Osteoblasts and osteoclasts were identified by alkaline
      phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP), respectively,
      whereas chondrocytes were identified morphologically. At sites of endochondral
      and intramembranous bone formation, TR-beta 1 and the splice variant -alpha 2
      were widely expressed by proliferating, mature, and hypertrophic chondrocytes and
      also in cells within the fibrous tissue and at the bone forming surfaces,
      respectively. They were also detected in osteoblasts, osteoclasts, and a few
      osteocytes at sites of bone remodeling. In contrast, TR-alpha 1 was the least
      expressed and was present mainly in osteoblasts at remodeling sites and in a few
      mature and undifferentiated chondrocytes. Our results show, for the first time,
      the presence and distribution of TRs in human bone in situ and suggest that the
      skeletal actions of thyroid hormones may be mediated via these receptors. Further
      studies are required to define the role of the individual receptor isoforms in
      bone metabolism.

PMID- 9267687
TI  - Osteoclasts generate cross-linked collagen N-telopeptides (NTx) but not free
      pyridinolines when cultured on human bone.
AB  - Urinary excretion of the cross-linked alpha 2(I) N-telopeptide (NTx) of type I
      collagen has proven in clinical studies to provide a highly responsive and
      specific index of bone resorption. In order to understand better the biological
      basis of the specificity and responsiveness of this marker, we examined whether
      osteoclasts cultured on human bone could generate immunoreactive NTx peptide.
      Mouse bone marrow cultures stimulated with 1,25 diliydroxyvitamin D3
      (1,25(OH)2D3) and hydrocortisone to produce osteoclasts, were cocultured on human
      bone particles or dentin slices. Aliquots of culture medium were assayed for NTx
      by enzyme-linked immunosorbent assay (ELISA). NTx was detected in the medium 5
      days after the addition of bone and continued to be produced linearly over the 14
      day culture period. NTx production required attachment to the bone particles or
      dentin slices of mononuclear and multinuclear cells that stained for tartrate
      resistant acid phosphatase. Surface area of resorbed dentin was highly correlated
      with medium NTx concentration (R2 = 0.84). Production of NTx was suppressed by
      the osteoclast inhibitors, calcitonin and alendronate, in a dose-dependent
      manner. Two other markers of bone resorption, hydroxylysyl pyridinoline and lysyl
      pyridinoline, were found in peptide linkage in the culture medium but not in free
      form; indicating that the osteoclasts had degraded the bone collagen to peptides
      but not to the free cross-linking amino acids.

PMID- 9267689
TI  - ETA receptor mediates the signaling of endothelin-1 in osteoblast-like cells.
AB  - We previously reported that endothelin-1 (ET-1) stimulates phosphatidylcholine
      hydrolyzing phospholipase D independently of phosphoinositide hydrolysis in
      osteoblast-like MC3T3-E1 cells. In the present study, we investigated the
      characteristics of the receptors mediating ET-1-induced intracellular signaling
      pathway in MC3T3-E1 cells. Cyclo-D-Trp-D-Asp-Pro-D-Val-Leu (BQ123), a selective
      ETA receptor antagonist, significantly inhibited the ET-1-induced formation of
      inositol phosphates in a dose-dependent manner in the range between 22 nmol/L
      (IC50) and 2.2 mumol/L (IC50 x 100). On the contrary, N-cis-2,6
      dimethylpiperidinocarbonyl-L-gamma MeLeu-D-Trp(COOMe)-D-Nle-ONa (BQ788), a
      selective ETB receptor antagonist, had no effect on the ET-1-induced formation of
      inositol phosphates in the range between 1.2 nmol/L (IC50) and 120 nmol/L (IC50 x
      100). BQ123 significantly suppressed the ET-1-induced formation of choline dose
      dependently, however, BQ788 did not affect the choline formation. BQ123 also
      inhibited the ET-1-induced release of arachidonic acid, but BQ788 had little
      effect. The results strongly suggest that ETA receptor mediates the three
      intracellular signaling pathways of ET-1: (1) phosphoinositide hydrolysis by
      phospholipase C; (2) phosphatidylcholine hydrolysis by phospholipase D; (3)
      arachidonic acid release in osteoblast-like cells.

PMID- 9267690
TI  - Tetracycline prevents cancellous bone loss and maintains near-normal rates of
      bone formation in streptozotocin diabetic rats.
AB  - The skeletal consequences of streptozotocin-induced (STZ) diabetes in the rat are
      characterized by decreased bone formation and, consequently, reductions in bone
      mass. Given the ability of tetracyclines to inhibit the breakdown of connective
      tissue collagen in experimental diabetes (and in other diseases), we examined the
      potential of this drug to prevent the osteopenia associated with STZ diabetes. To
      evaluate drug efficacy, the cortical and trabecular bone histomorphometry were
      analyzed and compared between vehicle-treated control and diabetic rats and
      control and diabetic rats treated orally with 20 mg/day of minocycline, a
      semisynthetic tetracycline. In addition, blood and urine glucose, body weight
      change, tibia lengths, cortical bone densities, and bone ash content were
      compared. At the end of the 26 day experimental period, diabetic (D) and
      minocycline-treated diabetic (MTD) rats were polyuric with reduced body weights
      and significantly elevated blood and urinary glucose levels (p < 0.01). Compared
      to control (C) and minocycline-treated control (MTC) animals, the periosteal and
      cancellous bone formation in the D rats had virtually ceased (p < 0.001), and the
      cancellous bone mass in the tibial metaphysis was reduced 47% (p < 0.01). In
      contrast, bone formation rates in the MTD animals were increased compared to the
      D rats (p < 0.001), while cancellous bone areas in the MTD animals were
      essentially equivalent to those observed in the C and MTC groups. Moreover,
      growth plate thickness, reduced 43% in the D rats, was preserved in the diabetic
      animals treated with minocycline. These results demonstrate that minocycline
      treatment of the streptozotocin diabetic rat maintains normal bone formation,
      normalizes growth plate thickness, and prevents cancellous bone loss.

PMID- 9267691
TI  - Fibroblasts of spinal ligaments pathologically differentiate into chondrocytes
      induced by recombinant human bone morphogenetic protein-2: morphological
      examinations for ossification of spinal ligaments.
AB  - To elucidate the process of ossification in spinal ligaments, an aqueous solution
      containing recombinant human bone morphogenetic protein (BMP)-2 (40
      micrograms/100 microL) was injected into murine ligamenta flava, and the
      ossification process was analyzed morphologically. In the control group, the
      solution administered lacked the protein; these flattened ligamentous fibroblasts
      possessing BMP receptors type IA and type II existed among type I collagen
      bundles. In the week immediately following the injection of BMP-2, ligamentous
      fibroblasts began to proliferate, differentiating into alkaline phosphatase
      positive chondrocytes surrounded by an extracellular matrix composed of type I
      and II collagen. By the second week, differentiated chondrocytes of various
      stages were observed in type II collagen-rich matrix. These chondrocytes showed
      an abundance of BMP receptors type IA and II. The pathologically induced
      cartilage was resorbed by chondroclasts, permitting migration of blood vessels
      and osteogenic cells, as well as providing a site for endochondral ossification.
      By the third week, BMP-induced ossification had compressed the spinal cord, and
      by the sixth week, the ligamentous tissue had been almost completely replaced by
      bone. Ligamentous fibroblasts appeared to possess BMP receptors, as well as the
      potentiality to differentiate into chondrocytes. BMP receptors were upregulated
      during chondrification of ligamentous fibroblasts induced by exogenous BMP-2,
      suggesting that BMPs may play an important role in ossification of spinal
      ligaments.

PMID- 9267692
TI  - Plasma levels of parathyroid hormone that induce anabolic effects in bone of
      ovariectomized rats can be achieved by stimulation of endogenous hormone
      secretion.
AB  - Parathyroid hormone (PTH) administration increases bone mass in normal and
      osteopenic animals. However, this treatment currently requires the daily
      injection of large amounts of PTH, and the relationship of these doses to plasma
      levels of PTH that are achievable physiologically is unknown. We determined in
      ovariectomized (ovx) rats: 1) the plasma PTH levels that occur after the
      subcutaneous injection of graded doses of rat PTH, 2) whether similar PTH levels
      can be achieved by stimulation of endogenous PTH secretion, and 3) whether a
      plasma PTH profile that is achievable physiologically is anabolic on bone.
      Injection of 1, 5, or 25 micrograms/kg rat PTH-(1-34) increased plasma PTH by 46,
      164, or 520 pg/mL, respectively, above basal levels within 60 min. Infusion of
      ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid for 2 h
      reduced plasma Ca2+ by 0.36 mmol/L and produced a total plasma PTH response (area
      under the plasma PTH curve) similar to that with the 5 micrograms/kg rat PTH
      injection. Then, 1, 5, or 25 micrograms/kg doses of rat PTH-(1-34) were injected
      subcutaneously daily for 28 days in 19-week-old rats that were ovx 7 weeks
      earlier. The 5 and 25 micrograms/kg doses significantly increased bone mineral
      density in the distal femur and trabecular bone area and average trabecular
      thickness in the proximal tibia. All doses of PTH significantly increased indices
      of trabecular connectivity and cancellous bone formation, including double
      labeled surface, mineralizing surface, and surface-referent bone formation rate.
      In conclusion, anabolic effects on bone can be achieved with a plasma PTH profile
      similar to that attained following stimulation of the parathyroid gland by
      induced hypocalcemia. These data suggest that agents that transiently increase
      endogenous PTH secretion may represent a novel means to promote anabolic effects
      in skeletal tissues.

PMID- 9267693
TI  - Pathogenesis of vitamin (A and D)-induced premature growth-plate closure in
      calves.
AB  - The pathogenesis of vitamin A-induced premature growth-plate closure was
      investigated in calves. A progressive increase in the severity of growth-plate
      lesions with time and a progressive increase in the extent of growth-plate
      involvement was observed. There was initial loss of metachromasia from the growth
      plate in a region that formed a narrow horizontal band of cartilage composed of
      the epiphyseal growth zone and a strip of reserve-zone cartilage. Immunostaining
      revealed there was loss of aggrecan, decorin, and biglycan from this region;
      however, it was doubtful that the regional loss of proteoglycan was a major
      contributing factor in the pathogenesis of premature growth-plate closure. This
      is because this region was the vestige of cartilage that remained when growth
      plate closure was almost complete. The major alteration was premature
      mineralization of columnar cartilage and subsequent endochondral ossification.
      This caused the depth of the columnar zone to be reduced. Columnar-zone cartilage
      cells appeared immature where the matrix became mineralized and lacked the
      morphology of hypertrophic chondrocytes. The depth of the reserve-cartilage zone
      also was reduced as matrix mineralization of the columnar zone progressed, and
      further reduction in columnar cartilage depth occurred. Eventually, there was
      matrix mineralization within the adjacent reserve cartilage. The distribution of
      reaction product after immunostaining with antibodies to the following proteins
      was described during normal endochondral ossification: aggrecan, decorin,
      biglycan, versican, type I collagen propeptide, type I collagen, type II
      collagen, osteopontin, osteocalcin, osteonectin, bone sialoprotein, and alkaline
      phosphatase. Biglycan, type I collagen propeptide, type I collagen, osteopontin,
      osteocalcin, osteonectin, bone sialoprotein, and alkaline phosphatase were
      localized within the cytoplasm or surrounding matrix of hypertrophic
      chondrocytes. In vitamin-treated calves, these same proteins were found in
      regions undergoing premature matrix mineralization even though the chondrocytes
      did not have a hypertrophic morphology. Therefore, vitamin treatment did not
      cause just a selective expression, but it caused expression of a large number of
      matrix proteins normally associated with the hypertrophic chondrocyte phenotype.
      Finally, completely mineralized columnar and reserve cartilage were removed by a
      modeling/remodeling process similar to that seen in the metaphysis.

PMID- 9267694
TI  - The ability of ultrasound velocity to predict the stiffness of cancellous bone in
      vitro.
AB  - The mechanical status of bones is an important consideration in skeletal
      pathological conditions such as osteoporosis, which result in fracture at
      predominantly cancellous bone sites. Density is a good predictor of the stiffness
      and strength of cancellous bone. However, these mechanical properties are also
      dependent on the cancellous bone's architecture. The objective of this work was
      to investigate the ability of ultrasound velocity to predict the Young's modulus
      of elasticity of cancellous bone. The cancellous bone specimens were 20 mm cubes
      from bovine femur and 21 mm diameter mediolateral cylinders cored from human
      calcaneus. Ultrasound velocity (V) and Young's modulus (E) were determined in
      three orthogonal directions for the bovine cubes [anteroposterior (AP),
      mediolateral (ML), and proximodistal (PD)], and mediolaterally in the calcaneus.
      Apparent density (p) was determined after the other tests. Density alone explains
      87.6% of the variance of Young's modulus in human calcaneal and bovine femoral
      bone tested in the PD direction only. Velocity, however, explains 95% and a
      combination of density and velocity 97%. Velocity and stiffness are not random
      with respect to the three directions in the bovine specimens. Further, for each
      cube we obtained the mean of the three values of E and of V, and characterized
      each value of E and V by their deviation from their mean. There is an extremely
      strong positive correlation (r = 0.80) showing that the degree of deviation is
      consistent for E and V, and of the same sign. These results demonstrate that the
      velocity of ultrasound in cubes of cancellous bone can give structure-specific
      information. In particular, knowledge of both density and velocity allows better
      predictions of stiffness than do density or ultrasound velocity on their own.
      Because there are noninvasive methods of measuring density that do not depend on
      ultrasonic measurement the combination of these two measurements promises,
      eventually, to give improved assessment of a bone's weakness and liability to
      fracture.

PMID- 9267695
TI  - Modeling the mechanical behavior of vertebral trabecular bone: effects of age
      related changes in microstructure.
AB  - Age-related reductions in the thickness and number of trabeculae in vertebral
      trabecular bone have been documented by several workers, yet the relative effects
      of these changes on mechanical properties are not known. We developed a two
      dimensional model of human vertebral trabecular bone and investigated its
      mechanical behavior using finite element analysis. The stress-strain behavior,
      failure mode, and strain distributions predicted using the model were consistent
      with those observed for vertebral trabecular bone under compressive loading.
      Random reductions in the number of trabeculae reduced the modulus and strength of
      the models two to five times more than uniform reductions in the thickness of
      trabeculae that caused the same loss of bone volume. For example, randomly
      removing longitudinal trabeculae to achieve a reduction in density of 10% reduced
      the strength by approximately 70%, whereas removing the same amount of bone by
      uniformly reducing the thickness of the longitudinal trabeculae only reduced the
      strength by approximately 20%. For a simulation of aged bone, in which the
      thickness and number of trabeculae were reduced concurrently, the strength was
      23% of its intact ("young") value. When the bone mass of the aged model was
      restored to its intact level by increasing the thickness but not the number of
      trabeculae, the strength increased by 60%, but was still only 37% of its intact
      value. These combined findings, based on a two-dimensional, idealized model of
      vertebral trabecular bone, illustrate the importance of maintaining trabecular
      number and suggest that it may not be possible to restore bone strength following
      a period of advanced bone loss if a substantial number of trabeculae have been
      resorbed. Thus, until treatments exist that can increase trabecular number, the
      most effective treatment strategy is to prevent the degradation of bone strength
      by maintaining the number of trabeculae at a healthy level.

PMID- 9267696
TI  - Polymerase chain reaction-based technique for the selective enrichment and
      analysis of mosaic arg201 mutations in G alpha s from patients with fibrous
      dysplasia of bone.
AB  - Mutations in the arg201 codon of the alpha s G protein-subunit have been
      associated with a variety of disorders, but analysis of such mutations has been
      complicated by their mosaic presentation. To overcome the problems associated
      with the analysis of genomic mutations that may be present in low and variable
      yield throughout the body, a polymerase chain reaction (PCR)-based technique has
      been developed that allows the selective amplification of products from the
      mutant allele. This technique uses site-directed mutagenesis to generate a PCR
      product from the normal allele that is susceptible to restriction endonuclease
      digestion, whereas that from the mutant allele is resistant to digestion.
      Consecutive and repeated cycles of amplification and digestion allow selective
      enrichment of the product from the mutant allele. The technique has been applied
      to the analysis of patients with fibrous dysplasia of bone, where the consequence
      of G alpha s mutations may vary from monostotic to polyostotic lesions, and has
      been performed with DNA isolated from either bone biopsy specimens or peripheral
      blood leukocytes. In addition to the previously described arg-->his and arg-->cys
      substitutions, the analyses have detected a novel arg-->ser substitution in one
      of the patients. This patient presented with a panostotic disease and may
      represent a unique subgroup of fibrous dysplasia.

PMID- 9267697
TI  - Reductions in bone strength after fluoride treatment are not reflected in tissue
      level acoustic measurements.

PMID- 9267698
TI  - Oxidative stress in cyclosporin and azathioprine treated renal transplant
      patients.
AB  - The major cause of death following transplantation is cardiovascular disease.
      Among the many processes involved in atherogenesis, oxidative stress and
      modification of low density lipoprotein has been assigned a major role. This in
      turn may be affected by the immunosuppressive regime used. We studied oxidative
      stress in 40 renal transplant patients receiving two different immunosuppressive
      regimens (20 on cyclosporin, 20 on azathioprine/prednisolone), and 19 normal
      controls. Changes in lipid peroxidation (assessed as thiobarbituric acid reacting
      substances, TBARS), antioxidant enzyme activities (glutathione reductase GSHPx,
      glutathione peroxidase GSHPx and superoxide dismutase SOD) vitamin E and
      antioxidant associated trace metals (selenium, copper, zinc) were studied.
      Alteration of erythrocyte membrane fluidity was examined using the fluorescent
      probe 1,6 diphenyl-1,3,5-hexatriene (DPH). Both transplant groups showed no
      difference in TBARS, lipid standardised vitamin E, copper or selenium compared to
      controls. Zinc was significantly increased in both the cyclosporin and
      azathioprine groups compared to controls (P < 0.05). SOD was reduced in both
      transplant groups compared to controls (P < 0.001). GSHPx was elevated in both
      groups compared to controls but only reached significance in the azathioprine
      treated group (P < 0.005). GSHRx was slightly elevated in both transplant groups
      but did not reach significance. Erythrocyte membrane anisotropy was decreased in
      the cyclosporin treated group (P < 0.05). There was no difference in the
      azathioprine group compared to controls. The present results suggest an adaptive
      response to increased oxidative stress in both transplant groups sufficient to
      minimise markers of oxidative stress (TBARS and anisotropy). The results also
      suggest no significant difference between the two immunosuppressive regimes with
      regard to oxidative stress.

PMID- 9267699
TI  - Degradation of glycated hemoglobin. Role of erythrocytic proteolytic enzymes and
      oxidant damage.
AB  - Glycated hemoglobin can be degraded by proteolytic enzyme(s) in the erythrocyte.
      The enzyme(s) co-elutes with glycated hemoglobin when the latter is separated
      from erythrocyte lysates using the cation-exchanger Bio Rex-70. A further
      purification of the Bio Rex eluant on DEAE Sephadex A-50 separated the enzyme(s)
      from glycated hemoglobin. Studies with the Bio Rex eluant showed that degradation
      of glycated hemoglobin is maximum at 37 degrees C at pH 8.6. Proteolytic
      degradation is inhibited by 5 mM N-ethylmaleimide (NEM), 5 mM ethylenediamine
      tetraacetic acid (EDTA) and 0.6 mM n-p-tosyl-L-lysine choromethyl ketone (TLCK)
      (100-87 and 76% inhibition respectively). This study also examines the
      possibility that oxidative-damage to glycated hemoglobin increases its
      susceptibility to proteolytic degradation. When incubated with various anti
      oxidants like DTPA, uric acid, mannitol and butylated hydroxy toluene (BHT),
      proteolytic degradation of glycated hemoglobin decreased by 66.1, 50.7 and 38%
      respectively.

PMID- 9267700
TI  - Incomplete or absent acute phase response in some postoperative patients.
AB  - In a prospective study, 74 patients were admitted for an open fracture of the
      lower limb and treated by osteosynthesis. None of them presented infectious
      complication during the postoperative period. Among them, 67 exhibited a
      classical acute phase response. In 5 patients, the response was apparently
      incomplete since no serum C-reactive protein (CRP) rise was observed after the
      injury; i.e. CRP concentrations remained inferior to the detection limit of the
      assay used; in contrast, serum alpha-1 acid glycoprotein (AAG) concentrations
      were temporarily increased, a variation associated with a concomitant decrease of
      transthyretin (TTR) concentration. In 2 other patients, CRP and AAG levels were
      not significantly modified. The 7 patients did not suffer hepatic insufficiency
      or protein malnutrition. In our series, incomplete or absent acute phase response
      was not rare (prevalence 9%) and was not related to an increased risk of
      postoperative infection. In contrast to CRP, the TTR response, i.e. a transitory
      decrease, was observed in all the 7 patients.

PMID- 9267701
TI  - Effect of a protein-rich meal on urinary and salivary free amino acid
      concentrations in human subjects.
AB  - The aim of the present study was to investigate whether in healthy volunteers
      acute changes in plasma free amino acid composition after a protein-rich test
      meal are reflected in the urinary and salivary concentrations of the
      corresponding amino acids. The ingestion of a protein-rich meal elicited a
      significant increase of plasma and urine amino acid concentrations. The
      postprandial salivary amino acid excretion showed only minor changes. For several
      amino acids (alanine, arginine, asparagine, glycine, threonine and valine)
      significant relations were observed between the increase in concentration of
      these amino acids in venous plasma and urine. In whole saliva, only threonine and
      valine showed a significant relationship with the corresponding plasma
      concentration. Our data suggest that the urinary amino acid excretion of several
      amino acids has the potential for estimating short-term changes in plasma
      concentrations. Determination of salivary amino acid concentrations seems less
      appropriate for this purpose.

PMID- 9267703
TI  - Fast 5-hour determination of angiotensin-converting enzyme genotypes from blood
      by SDS-PAGE using PhastSystem.
AB  - Polymorphism in the angiotensin-converting enzyme (ACE) gene has been shown to
      correlate with circulating ACE concentrations in plasma, and also to be an
      independent risk factor in the development of many cardiovascular diseases.
      However, methods available today for ACE genotyping are still laborious and time
      consuming. Here we report a sensitive, simple and non-isotopic procedure with
      commercially available gels for the identification of ACE insertion/ deletion
      polymorphism. This technique includes rapid extraction of the DNA by the QIAamp
      Blood Kit prior to polymerase chain reaction, followed by sodium dodecylsulphate
      polyacrylamide gel electrophoresis using the PhastSystem (Pharmacia). The
      procedure can be accomplished in five-hours from drawing the blood samples to the
      final result.

PMID- 9267702
TI  - Plasma polymorphonuclear leukocyte elastase levels and its relation to disease
      activity in psoriasis.
AB  - Although some increased enzyme activities in PMN leukocytes isolated from the
      circulation of psoriatic patients have been previously described, none of these
      enzymes had been studied in plasma for determination of disease activity. The
      purpose of this study was to evaluate whether plasma PMN elastase levels might be
      a good marker for determination of disease activity of psoriatic patients. Plasma
      PMN elastase and some acute phase reactants including alpha-1 antitrypsin, alpha
      2 macroglobulin, fibrinogen, erythrocyte sedimentation rate(ESR), and transferrin
      were studied in thirty-nine patients with psoriasis, including 16 controlled
      patients, and forty healthy control subjects. PMN elastase and the acute phase
      reactants except transferrin were found to be significantly higher in the
      psoriatic patients than in control subjects. The PMN elastase level in the
      patients was about 6-fold higher than that of the control group. The PMN elastase
      levels in the patients in the inactive period was two-fold higher than in the
      control subjects. PMN elastase was found to correlate significantly with PMN
      leukocyte count and alpha-1 antitrypsin in active and inactive periods of the
      disease, but with fibrinogen and psoriasis area and severity index (PASI) only in
      the active period of the disease. We conclude that plasma PMN elastase level may
      be a more specific and sensitive inflammatory marker than alpha-1 antitrypsin,
      alpha-2 macroglobulin, ESR, and may be a good marker for diagnosis and follow up
      of the disease activity of the psoriatic patients.

PMID- 9267704
TI  - Comparison of four different phenylalanine determination methods.
AB  - The ISOLAB NCS phenylalanine determination kit has not been widely applied for
      neonatal screening and patient follow up in Europe until now. This method, based
      on fluorescence enhancement of a phenylalanine-ninhydrin reaction product by the
      dipeptide L-leucyl-L-alanine, was compared with three other procedures: (1) The
      Quantase kit (Shield Diagnostics) for enzymatic determination of phenylalanine,
      (2) the standard amino acid analysis by means of ion exchange chromatography, and
      (3) the Guthrie Test as a bacterial inhibition assay (BIA). Only authentic
      samples from PKU patients were evaluated: once with the NCS kit and at least once
      with one of the three other methods. There was good agreement between the results
      obtained by the NCS kit using dried blood specimens and either of the other three
      methods, as well as between the NCS kit using plasma samples and the Quantase kit
      and ion exchange chromatography. Plasma sample measurement by NCS proved
      advantageous because of the option of measuring each microtiter plate twice by
      resetting the calibrators, i.e. special standards for plasma samples could be
      used on the same plate. We conclude that this method should prove time saving and
      cost effective when both neonatal screening and patient follow up are carried out
      in the same laboratory.

PMID- 9267705
TI  - A new fluorometric method for measuring the action of C apolipoproteins on milk
      lipoprotein lipase.
AB  - Monolayer vesicles containing pyrene-labelled nonanoyltriglyceride (1-2
      ditetradecyl 3-pyrene nonanoyl glyceride) were used as a substrate to measure
      bovine milk lipoprotein lipase activity. The activation of lipoprotein lipase by
      synthetic fragments of apolipoprotein C II and apo C III was measured. Fragments
      30-78 and 43-78 had actions similar to that of the entire apo C II. Fragments 50
      78 and 55-78 were 50% active, fragment 60-78 was 10% active and fragment 66-78
      was inactive. Thus the activating capacity depended on the length of the
      carboxyterminal fragment. Replacing tyrosine 62 in apo C II by glycine removed
      all lipoprotein lipase activating capacity, while making Tyr 62 less accessible
      for binding to lipids and enzyme decreased apo C II activating capacity. Apo C
      III1 inhibited both basal lipoprotein lipase activity (no apo C II) and
      lipoprotein lipase activated by apo C II. Apo C III, fragment A (1-40) which did
      not bind lipids, had no inhibitory effect, while fragment B(41-79) had the same
      effect as whole apo C III,. Apo AI, AII and C I also inhibited lipoprotein
      lipase. The fluorometric assay is easy to perform, and suitable for metabolic
      studies such as fatty-acid exchanges between lipoproteins, as it produces no
      alteration in the reaction products. It also avoids the use of a radio-labelled
      substrate.

PMID- 9267706
TI  - In vitro proliferative response of human peripheral blood mononuclear cells to
      concanavalin A.
AB  - The proliferation response of human peripheral blood mononuclear cells (PBMC) to
      concanavalin A (con A) was tested in a medium with or without addition of fetal
      calf serum (FCS) or a serum substitute. The time profile of the proliferative
      response of PBMC to con A was different in cells cultured in a medium
      supplemented with or without FCS. This different pattern occurred for the con A
      induced DNA-synthesis as well as for the RNA- or protein-synthesis. The peak
      proliferation rate and the stimulation index of proliferation of human PBMC to
      con A was also higher when the cells were cultured in a medium with 10% FCS
      compared to cells cultured in a FCS-free medium. Substitution of the fetal calf
      serum by a serum substitute even induced a profound inhibition of the de novo
      synthesis of DNA in human PBMC. The results indicate that a lymphocyte
      proliferation response to con A can still be obtained in a culture medium where
      no FCS was added, although a weaker stimulation occurred in comparison to a
      culture medium with FCS. However, addition of a serum substitute caused a marked
      inhibition of the lymphocyte proliferation rate.

PMID- 9267707
TI  - A blood test for intestinal permeability and function: a new tool for the
      diagnosis of chronic intestinal disease in dogs.
AB  - We demonstrate that rhamnose, 3-O-methyl-D-glucose, D-xylose and lactulose may be
      quantified accurately in blood by HPLC and pulsed amperometric detection, thus
      enabling studies of intestinal permeability and function to be carried out using
      plasma samples. Prior to HPLC, the endogenous glucose was enzymatically modified
      to gluconic acid and the protein precipitated. The precision of the
      quantification of the sugars in plasma (CV: 2.2-5.7%; 8.7-10.6% at very low
      concentrations) compared well with the quantification in urine. The results for
      groups of 8 dogs with small intestinal bacterial overgrowth and 12 dogs with
      inflammatory bowel disease were shown to be significantly different from a group
      of 20 normal control dogs (P < 0.001), demonstrating the test's value as a
      diagnostic tool. The normal ranges in blood 2 h post oral administration were
      determined to be 0.05-0.17 for the lactulose/rhamnose ratio and 0.45-0.65 for the
      xylose/3-O-methylglucose ratio. This method may be employed advantageously when
      the collection of urine in intestinal permeability and function tests is
      difficult.

PMID- 9267708
TI  - Application of near infrared spectroscopy to the determination of haemoglobin.
AB  - Seventy-two whole blood samples were investigated to determine the relationship
      between their spectral data measured in the near infrared (NIR) wavelength region
      and haemoglobin content based on laboratory data determined by a routine standard
      method as reference. Blood samples were obtained from the 1st Department of
      Medicine, Imre Haynal University of Health Sciences. Donors were selected
      randomly without respect to age, sex, state of health or medical treatment, from
      apparently healthy volunteers as well as from ambulatory and hospitalized
      patients. NIR spectra were measured with a SPECTRALYZER 1025 (PMC) computerized
      spectrophotometer in the 1000-2500 nm wavelength region. The relationship between
      laboratory data and values of the second derivative (i.e. second order finite
      difference) of the log(1/TF) spectra measured at different wavelengths was
      determined by multiple linear regression (MLR) using three- and four-term linear
      summation equations. The cross-validated standard error of performance (SEP) for
      haemoglobin was 1.348 g dL-1 with a three term model and 1.251 g dL-1 with a four
      term model over the range from 5.9 to 20 g dL-1. This preliminary study indicates
      that NIR measurements can be directly related to haemoglobin content and can be
      used to determine haemoglobin content in human whole blood.

PMID- 9267709
TI  - Urinary microalbumin and retinol-binding protein assay for verifying children's
      nephron development and maturation.
AB  - In order to further understanding of the development and maturation of the renal
      tubular reabsorption and glomerular permeability functions for the determination
      of the clinical pathological manifestation and treatment processing of renal
      diseases, random urine samples were collected from healthy subjects aged from
      birth to 60 years. All the samples were stored frozen at -70 degrees C for 4
      months. The concentrations of the retinol-binding protein (RBP) and microalbumin
      (MALB) in urine were measured by enzyme-linked immunosorbent assay and at 492 nm
      with the microplate reader as a valuable marker of renal tubular and glomerular
      development and maturation The concentrations of RBP and MALB in urine gradually
      decrease with age. The level of RBP in urine is higher in children before 3 years
      than after 3 years (P < 0.01). The levels of MALB in urine is higher in children
      before 1 year of age than after 1 year (P < 0.01). Our results suggest that the
      development and maturation of the glomerular permeability functions and the renal
      tubular reabsorption are gradual and continuous processes from birth to
      adolescence but the key stage of their maturation may be at about 1 year and 3
      years respectively: and that the rate of the tubular development may be slower
      than that of the glomerular development. Our results also extend existing data
      for normal ranges of RBP and MALB in urine from neonates to adults.

PMID- 9267710
TI  - Reversal of accelerated renal allograft rejection with FK 506.
AB  - Although FK 506 has been shown to effectively reverse refractory renal allograft
      rejection, its ability to reverse accelerated renal allograft rejection as a
      primary agent has not been specifically addressed. Herein evidence of the ability
      of FK 506 to reverse accelerated renal allograft rejection is presented. A 16-yr
      old highly sensitized (PRA 75%) male underwent a second cadaveric renal
      transplant procedure. Despite induction immunosuppression with ATGAM,
      cyclosporine, azathioprine, and corticosteroids, a marked elevation in serum
      creatinine (1.6-->2.1 ng/dl) and reduction in urine output (4000 ml/d-->1000
      ml/d) were observed on the sixth post-transplant day. Renal allograft biopsy
      performed at that time revealed typical features of accelerated rejection
      including neutrophil margination in glomerular and interstitial capillaries, and
      C3, IgG, and fibrin deposition in glomerular and interstitial capillaries (by
      immunofluorescence). FK 506 therapy was promptly instituted and ATGAM therapy
      discontinued. Serum creatinine peaked within 3 d of FK 506 therapy (2.5 mg/dl)
      and subsequently progressively dropped to 1.2 mg/dl. Repeat biopsy on FK 506
      treatment day 12 revealed marked histologic improvement. Renal function remains
      excellent (1.3 mg/dl) 18 months after initiation of FK 506 therapy, and recurrent
      rejection has not been observed. This experience provides evidence that FK 506
      therapy may effectively reverse accelerated renal allograft rejection, and that
      it provides a means for treating antibody-mediated mechanisms of allograft
      rejection.

PMID- 9267711
TI  - Risk of renal cell carcinoma after kidney transplantation.
AB  - Between December 1968 and July 1995, 2372 renal transplant recipients were seen
      regularly in our outpatient clinic. 154 patients (6.5%) of these subsequently
      developed a malignant tumor. One of the most frequently observed malignancies was
      a renal cell carcinoma in the native kidneys, found in 12 patients (7.8%; i.e.
      0.5% of the total population), two of them with analgesic nephropathy and one
      with adult polycystic kidney disease. So-called acquired cystic kidney disease of
      the native kidneys was found in 73% of the patients with renal cell carcinoma. In
      the patients with renal cell carcinoma the median age at transplantation was 43.9
      (39-55) yr. The median time from onset of end-stage renal failure and from
      transplantation to the appearance of the tumor amounted to 117.3 (43-206) and
      75.8 (5-164) months, respectively. Despite nephrectomy, four patients died of the
      cancer (6-57 months). As a consequence we suggest a regular sonographic screening
      of the native kidneys twice a year in all renal transplant patients. As in
      dialysis patients, the main risk factors for the development of renal cell
      carcinoma seem to be so-called acquired cystic disease of the native kidneys and
      the underlying renal disease, such as analgesic nephropathy, and obviously not
      the immunosuppressive regimen after transplantation.

PMID- 9267712
TI  - Risk factors for prolonged hospitalization after kidney transplants.
AB  - A major variable in the cost of kidney transplants is the length of initial
      hospitalization. Using multivariate analysis, we studied risk factors for
      hospital stay > 10 d post-transplant. Between 1 January 1985 and 31 August 1995 a
      total of 1588 patients underwent first or second kidney transplants at the
      University of Minnesota. Antibody was used for 1 wk in cadaver donor recipients
      and for 2 wk in pediatric recipients (resulting in a long stay for all pediatric
      recipients). Adult living related donor recipients were immunosuppressed with
      triple therapy. Donor risk factors studied were age (< 15, 15-50, > 50 yr) and,-
      for cadaver recipients, preservation time (< 12, 12-18, 18-24, 24-30, > 30 h) and
      cause of death (trauma, cerebrovascular accident, or cardiac). Recipient risk
      factors studied were age (< 18, 18-55, > 55 yr); sex; transplant number; antigen
      mismatch; peak PRA; PRA at transplant (< 11, 11-50, > 50); diabetic status;
      pretransplant dialysis (vs. pre-emptive transplant); pretransplant cardiac,
      peripheral vascular, or respiratory disease; and delayed graft function (DGF)
      (dialysis in the first week vs. no dialysis). Risk factors were analyzed
      separately for living donor and cadaver donor recipients. For cadaver donor
      recipients, DGF was the major risk factor (p < 0.0001); others were age 55 yr (p
      = 0.03) and diabetes (p = 0.02). For living donor recipients, DGF was also a risk
      factor (p = 0.003); others were diabetes (p = 0.01), retransplant (p = 0.006),
      PRA at transplant > 50 (p < 0.0001), age > 55 yr (p = 0.02), pretransplant
      respiratory disease (p = 0.005), and pretransplant dialysis (p = 0.005). Because
      DGF was the major risk factor for a prolonged stay, we then studied risk factors
      for DGF using multivariate analysis. For cadaver donor recipients, risk factors
      were recipient weight > 90 kg (p = 0.004), preservation time 24 h (p = 0.03), PRA
      at transplant > 50 (p = 0.03), and donor age < 15 or > 50 yr (p = 0.002). For
      living donor recipients, risk factors were recipient age < 18 yr (p = 0.01),
      donor age > 50 yr (p = 0.03), female sex (p = 0.05), pretransplant respiratory
      disease (p = 0.1), pretransplant peripheral vascular disease (p = 0.05), and
      recipient weight > 90 kg (p = 0.1). From our data, a profile emerged of
      recipients likely to have a longer hospital stay. Important variables, either
      simultaneous with or related to DGF, include donor and recipient age, diabetes,
      pretransplant recipient weight, PRA at transplant, preservation time, and
      pretransplant respiratory or peripheral vascular disease.

PMID- 9267713
TI  - Pure red cell aplasia due to parvovirus B19 infection in solid organ
      transplantation.
AB  - Human parvovirus B19 disease is an infrequent but recognized rare cause of anemia
      in immunocompromised patients. A few cases of parvovirus B19 infections have been
      reported in transplant recipients, of those only four patients underwent renal
      transplantation. The primary immunosuppressive therapy in these patients included
      prednisone with either cyclosporine or tacrolimus. In one patient the disease was
      self-limiting, while in three others the hematocrit improved following 10-15 d of
      treatment with commercial intravenous immunoglobulin (IVIG). Herein, we report
      the fifth case of pure red cell aplasia due to parvovirus B19 infection in a
      renal transplant recipient who responded to a 5-d course of IVIG. To our
      knowledge, this is the first case of parvovirus B19 infection in a patient with
      solid-organ transplantation whose immunosuppressive regimen included both
      mycophenolate mofetil and tacrolimus and in whom an excellent clinical response
      was achieved with a short course of IVIG infusion.

PMID- 9267714
TI  - Bacterial translocation in organ donors: clinical observations and potential risk
      factors.
AB  - Thirty-nine solid-organ donors were evaluated to determine the incidence of
      bacterial translocation to mesenteric lymph nodes. In addition, clinical
      variables from 59 local recipients of renal allografts from these donors were
      examined to assess whether translocation in donors was associated with increased
      morbidity in the recipients of organs from node-positive donors. Ileocecal lymph
      node cultures were positive in 18 of 39 donors (46%). Sixteen donors (41%) were
      hypotensive [systolic blood pressure (SBP) < 90 mmHg] and 27 (69%) received blood
      product transfusions before organ donation. The presence of hypotension and blood
      product transfusion were associated with positive and negative cultures,
      respectively. In 24 (41%) of 59 organs transplanted from donors with periods of
      hypotension, significantly more (16 of 24, 67%) were associated with positive
      lymph node cultures than with negative cultures (8 of 24, 33%; p = 0.029). In
      recipients of organs from node-positive versus node-negative donors there was a
      trend toward higher incidence of infection (32% vs. 25%), need for hemodialysis
      post-transplant (29% vs. 23%), graft loss within 1 yr (24% vs. 19%), and lack of
      blood transfusion prior to organ procurement (43% vs. 23%), although these
      variables were not significantly different between the groups. Hypotension or
      inadequate resuscitation may contribute to increased bacterial translocation to
      mesenteric lymph nodes. The overall impact upon the recipients of organs from
      donors with demonstrable translocation to lymph nodes remains undefined.

PMID- 9267715
TI  - Bloodstream infections in liver transplant recipients receiving tacrolimus.
AB  - The microbial origin, timing, risk factors, and outcome of bloodstream infections
      (bacteremia and fungemia) were prospectively analyzed in 130 consecutive liver
      transplant recipients receiving tacrolimus-based immunosuppression; median
      followup was 3 yr. 22% (29/130) of the patients developed 36 episodes of
      bloodstream infections (0.28 episodes/patient). Bloodstream infections accounted
      for 36% (36/100) of all major infections. 81% (29/36) of bloodstream infections
      were due to bacteremia and 19% (7/36) due to fungemia (candidemia 14% and
      cryptococcemia 5%). Intravascular catheters were the most frequent source and
      methicillin-resistant Staphylococcus aureus was the most frequent pathogen
      causing bloodstream infections. 70% of the catheter related and all bacteremias
      due to intra-abdominal infections occurred < or = 90 d, whereas 75% of the
      bacteremias due to biliary source occurred > 90 d after transplantation. Length
      of initial post-transplant intensive care unit stay (p = 0.014) and readmission
      to the intensive care unit (p = 0.003) were independently significant predictors
      of bloodstream infections. 40% of the candidemias occurred within 30 d of
      transplantation and were of unknown portal, whereas the portal in all candidemias
      occurring > 30 d post-transplant was known (catheter, hepatic abscess, urinary
      tract). Mortality in patients with bloodstream infections was 52% (15/29) vs. 9%
      (9/101) in patients without bloodstream infections (p = 0.0001). In conclusion,
      intravascular catheters (and not intra-abdominal infections) have emerged as the
      most common source of bloodstream infections, and gram-positive cocci (S. aureus)
      as the predominant pathogens in bloodstream infections after liver
      transplantation.

PMID- 9267716
TI  - Quality of life of hepatitis B and C patients after liver transplantation.
AB  - Liver transplantation is an accepted treatment for end-stage liver disease due to
      hepatitis C (HCV), but remains controversial for patients with hepatitis B(HBV).
      Recently, the use of aggressive hepatitis B immunoglobulin (HBIg) to maintain
      hepatitis B surface antibody (anti-HBs) titers greater than 500 IU/L has been
      reported to improve outcome of transplantation for hepatitis B. The aim of this
      study was to compare the quality of life of patients transplanted for HBV using
      this regimen of HBIg immunoprophylaxis (group 1) to patients transplanted for HCV
      (group 2). The State-Trait Anxiety Inventory (STAI), Sickness Impact Profile
      (SIP), and a work survey were administered to two groups of patients. The STAI
      measured anxiety while the SIP evaluated physical and psychosocial function.
      Lower scores indicated less anxiety and dysfunction. Questions regarding hours
      worked prior to illness and hours worked after transplantation were administered
      to both groups. Group 1 included a majority of patients who were hepatitis B e
      antigen (HBeAg) positive prior to transplantation. Survey response was 13:16
      (81%) for group 1; and 17:24 (72%) for group 2. Group 1 revealed significantly
      lower scores than group 2 on the STAI and the overall SIP score. Group 1 reported
      working similar hours after transplantation as prior to illness while group 2 did
      not. Thus, patients transplanted for HBV and treated with aggressive HBIg
      immunoprophylaxis attained a higher quality of life than patients transplanted
      for HCV.

PMID- 9267717
TI  - Diagnosing cytomegalovirus disease in CMV seropositive renal allograft
      recipients: a comparison between the detection of CMV DNAemia by polymerase chain
      reaction and antigenemia by CMV pp65 assay.
AB  - The optimal diagnostic test for CMV disease in renal allograft recipients in a
      locality with a high CMV seropositive rate has not been fully determined. We
      compared the usefulness of the CMV pp65 antigenemia (CMV-Ag) assay with the
      detection of DNAemia by a nested polymerase chain reaction (PCR) method in
      diagnosing CMV disease in 56 renal allograft recipients, of whom 50 (89.2%) were
      CMV seropositive prior to transplant (tx). Positive CMV-Ag assays were found in
      126/281 samples (44.8%) of 27 patients (48.2%) of whom five had seven episodes of
      CMV disease. The remaining 22 patients were asymptomatic. The symptomatic
      patients had significantly higher median peak CMV-Ag levels than the asymptomatic
      patients [800 (160-1380) vs. 5 (1-604) per 2 x 10(5) peripheral blood leukocyte
      (PBL), p < 0.0001]. One hundred and eight samples were tested by both CMV-Ag and
      PCR methods. Out of the 108 samples, 89 showed concordant results (37 positive
      and 52 negative for both tests). Seventeen samples of 11 patients were CMV-Ag
      negative/PCR positive. Out of these 11 patients, two had CMV disease and the
      discrepancy in the results was due to blood samples taken after the start of
      ganciclovir therapy. Falsely negative PCR tests were found in two samples of two
      patients with positive CMV-Ag assays. With a outoff antigenemia level of 100 per
      2 x 10(5) PBL, the sensitivity, specificity, positive and negative predictive
      values for diagnosing CMV disease were 100, 96, 71.4 and 100%, respectively. On
      the other hand, CMV DNAemia was detected in many asymptomatic patients, and the
      PCR test results correlated poorly with the clinical manifestations of the
      disease. In symptomatic patients undergoing ganciclovir therapy, the
      quantification of antigenemia level allowed the assessment of treatment efficacy.
      In addition, positive CMV-Ag assays at the end of therapy were associated with
      the subsequent relapse of CMV disease in two patients. The high specificity,
      together with the short processing time of 4 h, make the CMV-Ag assay the test-of
      choice for diagnosing CMV disease in a renal transplant population with a
      predominance of CMV seropositive patients.

PMID- 9267718
TI  - Graft outcome in cadaver renal transplants treated with full-dose cyclosporine
      induction without antibody, irrespective of graft function.
AB  - Cyclosporine (CSA) induction has been shown to prolong delayed graft function
      which in turn may compromise graft outcome. In this study we report our
      experience with full-dose CSA induction without antibody treatment irrespective
      of graft function and stress the importance of achieving therapeutic CSA levels
      in the early post-transplant period. The records of 293 first cadaver renal
      transplant recipients who were transplanted between January 1992 and December
      1995 were reviewed. Patients were divided into those who had immediate graft
      function (IGF, n = 197) and the ones who had delayed graft function (DGF, n =
      96). Twenty-six (13%) patients in the IGF group and 27 (28%) patients in the DGF
      group experienced at least one episode of acute rejection (AR), (P = 0.002).
      Patient and graft survival rates at 1, 2 and 5 yr were similar in the IGF and DGF
      groups. Cox regression analysis revealed that the absence of both DGF and AR was
      independently associated with a 0.44 times lower risk of graft failure (P =
      0.06), whereas AR without DGF was associated with a 1.9 times increased risk of
      graft failure (P = 0.02). DGF, with or without AR, did not affect the risk of
      graft failure. Logistic regression analysis showed that DGF was associated with a
      3.6 times higher risk-of AR (P = 0.003). A non-traumatic cause of donor death and
      preservation time > 24 h were associated with 1.9 and 2.4 times higher risks of
      DGF (P = 0.01, P = 0.08), whereas female donor gender reduced the risk of DGF by
      0.6 (P = 0.1). In conclusion, our results suggest that full-dose CSA induction
      with achievement of therapeutic target levels in the early post-transplant period
      is associated with an acceptable graft outcome. Graft outcome was not compromised
      by delayed function, whereas acute rejection was an independent predictor of
      graft failure.

PMID- 9267719
TI  - Tacrolimus in pancreas transplantation: a multicenter analysis. Tacrolimus
      Pancreas Transplant Study Group.
AB  - This follow-up multicenter analysis is based on 362 pancreas allograft recipients
      at 14 institutions who were given tacrolimus between 1 May 1994 and 15 November
      1995. Three groups were studied: (1) recipients given tacrolimus initially for
      induction and maintenance therapy (n = 250; 215 without, 35 with, a concurrent
      bone marrow transplant), (2) recipients who converted to tacrolimus for rescue or
      rejection therapy (n = 89), and (3) recipients who converted to tacrolimus for
      other reasons (n = 23). Of 215 recipients without a bone marrow transplant in the
      induction group, 166 (77%) underwent a simultaneous pancreas-kidney transplant
      (SPK), 29 (14%) a pancreas transplant alone (PTA), and 20 (9%) a pancreas after
      previous kidney transplant (PAK). Initial antibody therapy was given to 185 (86%)
      recipients. All 215 received tacrolimus and prednisone; 202 (94%) also received
      azathioprine (AZA) and 11 (5%) mycophenolate mofetil (MMF). The most common side
      effects of tacrolimus were neurotoxicity in 21%, nephrotoxicity in 21%,
      gastrointestinal (GI) toxicity in 13%, and diabetogenicity in 13% of these
      recipients. No recipient in this group developed new-onset insulin-dependent
      diabetes mellitus. Of 89 recipients in the rescue group, 71 (79%) had an SPK, 11
      (13%) a PTA, and 7 (8%) a PAK. Before conversion, all had been on cyclosporine
      (CsA)-based immunosuppression; 74% of them had 2 or more rejection episodes
      previously. The most common side effects were nephrotoxicity in 27%,
      neurotoxicity in 26%, GI toxicity in 18%, and diabetogenicity in 8% of these
      recipients. No recipient in this group developed new-onset insulin-dependent
      diabetes mellitus. In the induction group patient survival at 1 yr was 98% for
      SPK, 79% for PTA, and 100% for PAK recipients. According to a matched-pair
      analysis, pancreas graft survival for SPK recipients at 1 yr was 88% with
      tacrolimus vs. 73% with CsA (p = 0.002); for PTA recipients, 68% vs. 70% (p >
      0.35); and for PAK recipients, 85% vs. 65% (p = 0.13). Graft loss from rejection
      was not different with tacrolimus vs. CsA in all 3 pancreas recipient categories.
      At 1 yr, 17% of recipients had converted from tacrolimus to CsA for
      diabetogenicity, nephrotoxicity, or rejection; 23% had converted from AZA to MMF.
      The incidence of post-transplant lymphoma was < 2%. In the rescue group, patient
      survival rates at 1 yr were 96% for SPK, 100% for PTA, and 86% for PAK recipients
      (p < 0.08). Pancreas graft survival at 1 yr was 89% for SPK, 58% for PTA, and 69%
      for PAK recipients (p = 0.004). Graft loss from rejection was significantly lower
      for SPK vs. PTA or PAK recipients. At 1 yr, 20% of recipients had reconverted
      from tacrolimus to CsA for rejection, neurotoxicity, or nephrotoxicity; 19% had
      converted from AZA to MMF. There were no post-transplant lymphomas in the rescue
      group. This follow-up multicenter analysis shows that tacrolimus after pancreas
      transplantation is associated with high graft survival rates when used for
      induction and with high graft salvage rates when used for rescue therapy. The
      rate of graft loss from rejection is low in all 3 pancreas recipient categories.
      The overall incidence of new-onset insulin-dependent diabetes mellitus is < 1%,
      as is the incidence of post-transplant lymphoma. Converting from tacrolimus to
      CsA and, in patients on tacrolimus, from AZA to MMF, is safe; interchangeable use
      of drugs appears to be of immunologic benefit. To determine the best
      immunosuppressive regimen after pancreas transplantation, a prospective
      randomized study comparing tacrolimus and MMF vs. Neoral plus MMF is mandatory.

PMID- 9267720
TI  - Anemia following renal transplantation: erythropoietin response and iron
      deficiency.
AB  - To define the etiology of anemia post-renal transplantation, we assessed
      hematologic parameters and EPO levels in 38 anemic and 16 non-anemic control
      renal transplant recipients (RTRs) with varying degrees of allograft function at
      periods > 3 months post-transplantation. Significant differences between the two
      groups were found for serum creatinine (Cr) 291.7 +/- 26.5 vs. 203.3 +/- 26.5
      mumol/l, p < 0.01; iron 9.3 +/- 0.92 vs. 13.6 +/- 1.7 mumol/l, p < 0.05; and
      ferritin 345.5 +/- 90.8 vs. 91.1 +/- 18.5 micrograms/l, p < 0.01. Serum EPO
      levels were inappropriately low in anemic patients with no significant
      correlation between EPO and Cr or hematocrit (Hct) levels. Serum iron was the
      only predictive factor for anemia on regression analysis (p < 0.05). Ferritin
      levels did not correlate with serum iron or Hct, and may be falsely elevated in
      iron deficient RTRs. Iron deficiency, poor renal function and inappropriately low
      EPO levels are major contributors to the 12% of our outpatient renal transplant
      population who are anemic.

PMID- 9267721
TI  - Treatment of steroid-resistant and recurrent acute cardiac transplant rejection
      with a short course of antibody therapy.
AB  - The purpose of this study was to assess the efficacy of short courses of OKT3 and
      ATG, respectively, for steroid resistant or recurrent acute allograft cardiac
      rejection (AR). Between June 1988 and March 1994, 101 heart transplant patients
      were treated with a quadruple sequential immunosuppression protocol (ATG,
      azathioprine, CsA, and prednisone). AR was diagnosed by endomyocardial biopsy
      (EMB), and patients with scores > 2 (ISHLT) received pulse methylprednisolone,
      500 mg i.v. on 3 consecutive days. In cases of steroid-resistant or recurrent AR,
      OKT3 (5 mg/d) or ATG (1.5-2.5 mg/kg/d), was administered for 5-7 d instead of the
      usual 10-14 d course. OKT3 (17 courses; 10 steroid resistant, 7 recurrent AR; 5.3
      +/- 0.7 doses) was given to 16 patients (4F/12M, 45 +/- 11 yr), 29-269 d after
      transplantation. ATG (8 courses; 5 steroid resistant, 3 recurrent AR; 4.9 +/- 0.6
      doses) was given to 8 patients (1F/7M, 53 +/- 7 yr), 23-503 d after
      transplantation. Successful treatment of AR with a score < 2 at the first and
      second EMB after treatment was 88% and 88% with OKT3, and 87.5% and 100% with
      ATG, respectively. Throughout follow-up (50 +/- 22 months after OKT3; 49 +/- 28
      months after ATG), there was a trend towards lower incidence of subsequent AR
      after ATG (25% vs. 69%, P = 0.09), and similar incidence of infections, graft
      atherosclerosis and mortality. No cases of lymphoproliferative disorder were
      observed. We conclude that short courses of OKT3 or ATG are safe and effective
      for the treatment of steroid resistant or recurrent AR, with a similar incidence
      of complications. These results may have cost-effectiveness implications and need
      to be confirmed in a randomized study.

PMID- 9267722
TI  - Leuconostoc bacteremia after liver transplantation: another cause of vancomycin
      resistant gram-positive infection.
AB  - Leuconostoc sp. are gram-positive bacteria intrinsically resistant to vancomycin,
      which can be confused with streptococci based on routine microbiological
      characteristics. Infections secondary to Leuconostoc are uncommon, and usually
      affect patients with underlying diseases, prior use of vancomycin and those with
      central lines. The most common clinical presentation is fever secondary to a
      central line infection. We report the first case of Leuconostoc infection in a
      solid organ transplant recipient. The patient developed Leuconostoc bacteremia
      secondary to peritonitis, 60 d after undergoing liver transplantation. He was
      treated with clindamycin, gentamicin and underwent surgical debridement, but
      succumbed to other complications.

PMID- 9267723
TI  - Changes in phenotypes of apolipoprotein E and apolipoprotein(a) in liver
      transplant recipients.
AB  - The aim of this study has been to confirm that liver is the main site of
      apolipoprotein (apo) E and apo(a) synthesis, based in the changes of their
      phenotypes after transplantation. Apo E phenotypes were studied in 34 patients
      and apo(a) phenotypes in 27 of them before and after liver transplant. Thirteen
      patients changed the apo E phenotype after transplantation. Eight patients with
      E3/3 phenotype changed to the others with 2 or 4 alleles. Three patients with
      E4/3 phenotype changed to E3/3, one changed from E3/2 to E3/3 and another one
      changed from E4/2 to E3/2 phenotype after transplantation. Twenty one of the 27
      patients changed the apo(a) phenotype. Thirteen of them also changed lipoprotein
      (Lp)(a) serum concentration at least twofold, showing in 11 an increase and in 2
      a decrease, in relation with the change to phenotype associated with high and low
      Lp(a) concentration, respectively. Changes in apo E and apo(a) phenotypes in
      liver transplant recipients studied show that most of these apolipoproteins are
      synthesized by the liver.

PMID- 9267724
TI  - Induction immunosuppressive therapy is associated with a low rejection rate after
      liver transplantation.
AB  - Despite advances in immunosuppression, allograft rejection occurs frequently
      after liver transplantation. The use of induction therapy with cytolytic
      antibodies may decrease the frequency of rejection in liver transplant
      recipients, but may also increase the rate of cytomegalovirus (CMV) infection. It
      has been our center's strategy to use induction therapy in our liver transplant
      recipients. To determine the outcome of our strategy, we retrospectively reviewed
      all liver transplants performed in the first 5 yr of our liver transplant
      program. The frequency of acute rejection in the first year after liver
      transplantation was only 34% in patients who received induction therapy. The type
      of induction therapy antibody did not affect the rejection rate. Clinically
      significant CMV infection (requiring treatment) occurred in 22% of patients.
      These results suggest that use of induction therapy with cytolytic antibodies
      does not lead to a high incidence of CMV infection and decreases the incidence of
      rejection after liver transplantation.

PMID- 9267725
TI  - Predictors of progression of diabetic nephropathy: implication for timing of
      kidney transplantation.
AB  - Multiple risk factors are important predictors in the development of diabetic
      nephropathy (DN). Once DN has developed, it progresses steadily to renal failure.
      To determine the rate of renal function decline and the parameters that influence
      the rate of decline, we retrospectively reviewed the charts of patients with DN
      who had undergone dialysis or kidney transplantation at the Mayo Clinic from 1983
      to 1993. Forty patients were found to have two or more iothalamate clearance
      (IothmCl) measurements where a slope of renal function decline over time,
      expressed as mL/ min/month/1.73 m2, can be calculated. The parameters examined
      included age of onset and duration of diabetes (DM); age at initial presentation,
      insulin dosage, glycosylated hemoglobin level, proteinuria, blood pressure (BP),
      number of antihypertensive medications (HTM), use of ACE inhibitors, creatinine,
      and initial IothmCl. The mean overall decline of clearance was 1.36 +/- 1.1
      mL/min/month, corrected. Univariate regression analysis showed that only systolic
      and mean BP (p < 0.05), use of HTM (p = 0.02), and the number of HTM used (p =
      0.0001) correlated with the rate of clearance decline. No other parameter was
      significant. The decline of IothmCl was 0.72 +/- 0.41, 1.20 +/- 0.9, and 2.34 +/-
      1.38 mL/min/month, for patients taking no HTM, < 3 HTM, and > or = 3HTM,
      respectively. Of the eight patients on HTM who presented with initial IothmCl of
      < 30 mL/min/1.73 m2, seven (88%) had clearance of < 10 mL/min/1.73 m2 within 1
      yr. We conclude that hypertension is an important marker of DN progression, and
      that the more HTM required for control of BP, the faster the decline of renal
      function. We recommend that a suitable transplant candidate with DN who presents
      with hypertension requiring HTM and a clearance of < 30 mL/min should be placed
      on the transplant waiting list.

PMID- 9267726
TI  - Variations of the intrahepatic bile ducts: application in living related liver
      transplantation and splitting liver transplantation.
AB  - The variations in the anatomy of intrahepatic bile ducts complicate operations in
      living related liver transplantation (LRLT) and therefore preoperative
      delineation of the biliary system is important to achieve a successful outcome.
      The aim of this study was to establish a standard relationship between the
      biliary variations and the methods of the graft splitting and anastomosis. Of 958
      endoscopic retrograde cholangiographies with good visualization of bile duct
      branches were selected and were available for evaluation of their ramifications
      and variants. According to drainage of right hepatic duct and left hepatic duct,
      we classified the bile ducts into two major groups. Unusual routes of the
      intrahepatic ducts were present in 105 cases (11% in group A) the right sectoral
      duct drained into the left hepatic duct directly; in 200 cases (21% in groups B)
      the duct of segment IV drained into right side or common hepatic duct; and in 29
      cases (3% in groups B) the duct of segment: II and III drained into the CBD and
      right hepatic duct separately. There is no specific bile duct variation that
      forbids someone from LRLT and SLT, but unusual intrahepatic ducts routes may
      require a change both in the cutting plane during graft retrieval and pattern of
      ductoenteral anastomosis to avoid potential complications to both donors and
      recipients. Cholangiography for screening intrahepatic duct variations is
      therefore important for safe bile drainage for both donors and recipients.

PMID- 9267727
TI  - Combined kidney-pancreas and parathyroid transplantation: a case report.
AB  - We report the first successful multiorgan kidney-pancreas and parathyroid tissue
      transplant in a patient with autoimmune polyglandular syndrome and medullary
      cystic disease. Successful transplantation included quadruple drug induction
      therapy consisting of antithymocyte globulin, azathioprine, cyclosporine and
      prednisone. All three grafts are functioning 2 yr after transplantation.

PMID- 9267728
TI  - Prevalence of hepatitis C virus antibodies and evaluation of hepatitis C virus
      genotypes in patients with lichen planus.
AB  - BACKGROUND: Several cases of lichen planus (LP) associated with hepatitis C virus
      (HCV) infection have been described. The reported prevalence rates of anti-HCV in
      patients with LP show wide geographical variations. An association of HCV
      associated disorders with certain HCV geno/subtypes has not been investigated so
      far. OBJECTIVE: The aim of the present study was to define the prevalence rate of
      anti-HCV in German patients with LP and to determine the distribution of HCV
      geno/subtypes. METHODS: All patients with LP of the present study (n = 84) were
      tested for anti-HCV antibodies by an enzyme-immunoassay (second generation). HCV
      RNA was detected by reverse-transcription polymerase chain reaction (RT-PCR) and
      HCV geno/subtyping was performed by the reverse hybridization assay. Serum
      samples of 87 patients with various cutaneous diseases excluding LP served as
      control group. RESULTS: Anti-HCV antibodies were detected in 13/84 patients with
      LP (16%), and 12/13 anti-HCV-positive patients were viraemic as assessed by the
      presence of HCV RNA. Most patients were infected with subtype HCV-1b (10/12
      patients), while the 2 remaining patients were infected with HCV-2b and HCV-3a,
      respectively. In the control group, anti-HCV antibodies were only observed in
      1/87 patients (1.1%), infected with subtype HCV-1b. CONCLUSION: The statistically
      significant (p < 0.002) high prevalence of HCV RNA in patients with LP is
      suggestive of an aetiological role of HCV in the pathogenesis of LP. Compared to
      the geno/subtype distribution of patients with chronic hepatitis C without LP of
      the same geographical area, no convincing correlation between geno/subtype and
      the presence of LP was obtained.

PMID- 9267729
TI  - Producibility of exfoliative toxin and staphylococcal coagulase types of
      Staphylococcus aureus strains isolated from skin infections and atopic
      dermatitis.
AB  - BACKGROUND: Strains of Staphylococcus aureus which cause staphylococcal scalded
      skin syndrome (SSSS) and bullous impetigo secrete exfoliative toxin (ET). Two
      antigenically distinct serotypes of ET, ETA and ETB, have been reported.
      MATERIALS AND METHODS: Two hundred eighty-three strains of S. aureus isolated
      from impetigo, SSSS, furuncles (including furunculosis) and atopic dermatitis
      were examined in terms of the producibility of ET, ET serotypes and coagulase
      types. We examined ET production and ET serotypes using the polymerase chain
      reaction with the oligonucleotide primers for eta and etb. RESULTS: The incidence
      of ET producers was 69.4% (100/144) in impetigo, 100% (6/6) in SSSS, 2.8% (3/112)
      in atopic dermatitis and 0% (0/21) in furuncles. ETA alone was produced by 57
      strains from impetigo and by 3 strains from atopic dermatitis. ETB alone was
      produced by 36 strains from impetigo and by all 6 strains from SSSS. Seven
      strains from impetigo produced both ETA and ETB. Most ETA producers belonged to
      coagulase type V and most ETB producers to coagulase type I. Impetigo strains
      mostly belonged to type I or V. All strains from SSSS were classified as type I.
      Type IV was most frequent among S. aureus isolates from furuncles. CONCLUSION:
      These results add to the epidemiological information as to ET producibility and
      ET serotypes of S. aureus strains isolated from impetigo, SSSS, furunculosis and
      atopic dermatitis. We have found that there is a relationship between the ET
      serotypes and the coagulase types of ET-producing strains.

PMID- 9267730
TI  - Clinical validation and guidelines for the SCORAD index: consensus report of the
      European Task Force on Atopic Dermatitis.
AB  - BACKGROUND: We have previously reported how the SCORAD index was designed. This
      cumulative index combines objective (extent and intensity of lesions) and
      subjective (daytime pruritus and sleep loss) criteria. AIMS: To study
      interobserver variability in scoring for objective SCORAD criteria and to
      optimize the scoring guidelines. MATERIAL AND METHODS: Three scoring sessions
      were organized in 1993-1994 in Hamburg, Bordeaux and Rotterdam totalizing 19
      patients (14 children and 5 adults) and 23 physicians, among whom 12 participated
      in at least 2 scoring sessions; 169 evaluation sheets have been processed using
      the SCORAD File Marker Pro software. At each session, total body photographs and
      close-up views were taken of each patient, and this material was reviewed at the
      final evaluation. RESULTS: The extent of lesions according to the rule of nines
      showed interobserver variability mostly for patients with lesions of moderate
      intensity involving 20-60% of body surface. Intensity items were scored with more
      consistency overall, but variations subsided especially for oozing/crusts and
      lichenifications. Low and high scorer profiles and the benefit of training were
      noted. CONCLUSIONS: This study has allowed to optimize clinical scoring using the
      SCORAD system. A proposal has been made to grade the severity of atopic
      dermatitis according to objective criteria in three groups for inclusion in
      clinical trials. The SCORAD index remains the major criterion for follow-up in
      trials.

PMID- 9267731
TI  - Cancer proneness of linear porokeratosis may be explained by allelic loss.
AB  - BACKGROUND: It is well known that porokeratosis, a genetically heterogeneous
      disorder characterized by the histopathological feature of the cornoid lamella,
      shows an increased proneness to develop carcinoma. On the other hand, a
      significant mechanism in the origin of many forms of cancer is loss of
      heterozygosity or allelic loss. OBJECTIVE: Because it has recently been proposed
      that linear porokeratosis may result from allelic loss, one might expect that
      linear porokeratosis is especially prone to malignant degeneration. In order to
      test this hypothesis, a review of case reports was performed. METHOD: Cases of
      cancer-associated porokeratosis were collected from the European language
      literature and assigned to one of 5 different types [plaque type of Mibelli (PM);
      disseminated actinic superficial porokeratosis (DSAP); porokeratosis palmaris,
      plantaris et disseminata (PPPD); porokeratosis punctata palmaris et plantaris
      (PPPP); linear porokeratosis (LP)]. RESULTS: Malignant or premalignant lesions
      were reported in 9 cases of PM, 15 cases of DSAP, 3 cases of PPPD, 1 case of PPPP
      and 21 cases of LP. CONCLUSION: This analysis supports the view that among the
      various forms of porokeratosis, the linear type is particularly susceptible to
      malignant degeneration. Arguments are presented in favor of the assumption that
      the genetic mechanism of allelic loss giving rise to LP may represent an initial
      step in the development of cancer.

PMID- 9267732
TI  - The cutaneous-vulvar clinic revisited: a 5-year experience of the Columbia
      Presbyterian Medical Center Cutaneous-Vulvar Service.
AB  - OBJECTIVE: To review the recent experience of a busy referral cutaneous-vulvar
      service. STUDY DESIGN: 500 randomly chosen charts from the last 5 years of
      patients seen at the Columbia Presbyterian Medical Center Cutaneous-Vulvar
      Service were reviewed. Information was entered into a computer data base and
      analyzed. RESULTS: The most common presenting condition was vulvar vestibulitis
      (36.2%), followed by lichen sclerosus (19.2%) and vaginitis/vaginosis (14.8%).
      Most patients had undergone a variety of therapies prior to referral. Many were
      treated for moniliasis in the absence of clinical evidence prior to our
      evaluation. Most patients responded well to appropriate therapy. CONCLUSIONS: A
      variety of primary care providers see women with cutaneous-vulvar symptomatology.
      Awareness of prevalent conditions will lead to correct diagnosis and treatment.
      We emphasize the importance of interdisciplinary consultation in difficult cases.

PMID- 9267733
TI  - Drug eruption induced by cyanamide (carbimide): a clinical and histopathologic
      study of 7 patients.
AB  - BACKGROUND: In some countries, cyanamide is used as an alcohol intake inhibitor
      with few harmful side effects. So far 3 cases of allergic contact dermatitis and
      only 1 of lichenoid drug eruption due to cyanamide have been reported. OBJECTIVES
      AND METHODS: We describe the clinical manifestations, course, histopathologic and
      immunohistochemical findings of 7 cases of cyanamide-induced drug eruption.
      RESULTS: Of the 7 patients, 6 developed exfoliative dermatitis and 1 a lichen
      planus-like eruption. Three patients with exfoliative dermatitis showed high
      fever, severe itching, anorexia, insomnia and general malaise, suggesting the
      diagnosis of hypersensitivity reaction. In all cases, mononuclear cell
      infiltration in the upper dermis with epidermotropism and dyskeratosis of the
      epidermal cells were observed histopathologically. The infiltrating cells
      consisted mainly of T4-positive lymphocytes. CONCLUSION: The cyanamide-induced
      skin reaction may be included in the spectrum of lichenoid drug eruptions, and
      its incidence may be much higher than previously reported.

PMID- 9267734
TI  - Short- and long-term effectiveness of oral and bath PUVA therapy in urticaria
      pigmentosa and systemic mastocytosis.
AB  - BACKGROUND: Previous studies have shown that oral PUVA is effective in urticaria
      pigmentosa. Long-term results, however, are unknown. OBJECTIVE: We studied the
      long-term effectiveness of oral PUVA treatment in urticaria pigmentosa as well as
      in systemic mastocytosis. In addition, the success of bath PUVA was examined in
      these diseases. METHODS: Twenty patients with urticaria pigmentosa and systemic
      mastocytosis treated by oral PUVA were examined retrospectively for a time period
      of up to 18 years. We studied the duration of improvement and correlated these
      results with the total PUVA dose, the skin type and the age of onset. Four
      patients were treated by bath PUVA therapy. RESULTS: In oral PUVA therapy an
      improvement was seen in 14 out of 20 patients (70%). There was no difference in
      the response rate between urticaria pigmentosa and systemic mastocytosis and
      there was no correlation with the total PUVA dosage. The duration of the
      treatment's success ranged from a few weeks to more than 10 years. 25% of the
      patients showed an improvement for more than 5 years. Patients with onset during
      childhood and early adolescence and patients with skin types I and II responded
      favourably to the treatment. Bath PUVA therapy was without effect in our 4
      patients. CONCLUSION: Oral PUVA is very effective for the long-term treatment of
      urticaria pigmentosa as well as systemic mastocytosis.

PMID- 9267735
TI  - Radiation therapy in AIDS-related cutaneous Kaposi's sarcoma.
AB  - BACKGROUND: Treatment of cutaneous Kaposi's sarcoma associated with AIDS depends
      on localization, extension, associated symptoms and the patient's general
      condition. The most frequent sites of involvement are the face and neck. The aim
      of this retrospective study was to evaluate the response rate as well as the
      cosmetic results comparing two different schedules of palliative radiation
      treatment. METHODS: 251 Skin lesions in 22 patients were treated with irradiation
      using 100 kV X-ray energy. Applied doses varied between 8 Gy/1 fraction and 30
      Gy/10 fractions. The mean age of patients was 38 years (28-59 years). According
      to Mitsuyasu's staging, 2 patients had stage I, 8 stage II and 12 patients stage
      IV. The lesions were localized on the face (n = 190), lower extremities (n = 28),
      upper extremities (n = 24) and the thorax (n = 9). The total given dose was 30 Gy
      in 68 lesions (27%), 21 Gy in 11 lesions (4.4%), 20 Gy in 2 lesions (0.8%) and 8
      Gy in 170 lesions (67.8%). RESULTS: Complete response with or without residual
      pigmentation was achieved in 95.2% of lesions, while 4.4% had a partial response
      and 0.4% no response. Pain was completely relieved in all patients. CONCLUSIONS:
      Radiotherapy can be recommended as palliative treatment to relieve physical
      discomfort (pain) and to improve the cosmetic results in patients with AIDS
      related Kaposi's sarcoma. Doses ranging from 8 Gy/1 fraction to 30 Gy/10
      fractions, tailored to the individual patient's need, permit to achieve an
      excellent local control with minimal toxicity.

PMID- 9267736
TI  - Acetylator phenotype in patients with p-phenylenediamine allergy.
AB  - OBJECTIVE: p-Phenylenediamine (PPD) has been widely distributed as hair dye
      ingredient and may be responsible for contact dermatitis. Since not all the
      subjects exposed to PPD react to the substance, we tested a possible predisposing
      factor of cutaneous drug metabolism. METHODS: Eighty-five patients were selected
      on the basis of their patch test result for PPD. The acetylator status of
      patients was estimated using HPLC analysis of urinary caffeine metabolites.
      RESULTS: Among patients with a negative result for PPD, there were three groups,
      i.e. fast, intermediate and slow acetylators, just as in the healthy population.
      However, we could not find any rapid acetylator in the PPD-sensitive patient
      group, and slow acetylators were more often encountered in this group (p < 0.05).
      CONCLUSION: The acetylator phenotype might be a good marker for the cutaneous
      sensitivity to PPD.

PMID- 9267737
TI  - Granuloma annulare in a patient with malignant lymphoma.
AB  - We describe the case of a 69-year-old man with malignant lymphoma who developed
      granuloma annulare on his fingers. The number of cutaneous nodules increased when
      a recurrence of lymphoma was demonstrated during the course of disease.
      Granulomatous lesions disappeared after the fifth cycle of chemotherapy with CHOP
      (cyclophosphamide, Adriamycin, vincristine, prednisolone). The coexistence of
      these two diseases is relatively rare. The clinical features seen in this case,
      however, might suggest that granuloma annulare is a generalized granulomatous
      reaction induced by malignant lymphoma.

PMID- 9267738
TI  - Diclofenac: a new trigger of pemphigus vulgaris?
AB  - Many drugs have been shown to induce pemphigus, including thiol and nonthiol
      drugs. We present a case of pemphigus vulgaris where a nonsteroidal anti
      inflammatory medication, diclofenac in suppositories and topical gel
      preparations, is suspected of having triggered the disease. The temporal
      relationship between drug and outbreak of disease together with the positive
      migration inhibition factor test to diclofenac point to the possible involvement
      of this drug in triggering pemphigus vulgaris.

PMID- 9267739
TI  - A case of pyoderma gangrenosum stabilized with lymecycline, topical benzoyl
      peroxide and treated by autograft.
AB  - Pyoderma gangrenosum is a chronic inflammatory ulcerative skin disease of unknown
      etiology, often associated with various systemic disorders such as inflammatory
      bowel disease, rheumatoid arthritis, chronic active hepatitis, diabetes mellitus
      and hematologic malignancies. The ulcers are characterized by their undermined
      violaceous borders. The disease remains a therapeutic challenge. Corticosteroids
      are the mainstay of therapy; however, side effects from this treatment and
      recalcitrant pyoderma gangrenosum require therapeutic alternatives. We report the
      case of a large subacute pyoderma gangrenosum stabilized with lymecycline,
      topical benzoyl peroxide and successfully treated by an autograft. This
      observation supports the opinion that the risk of pathergy of a graft can be
      avoided by the stabilization of the disease.

PMID- 9267740
TI  - Necrotizing cutaneous lesions caused by interferon beta injections in a patient
      with multiple sclerosis.
AB  - We report a patient with multiple sclerosis who was receiving subcutaneous
      injections of recombinant interferon beta. During the third month of treatment,
      painful necrotizing cutaneous lesions appeared at the injection sites. The
      possible pathogenesis of interferon-induced skin necrosis is discussed.

PMID- 9267741
TI  - A case of extramammary Paget's disease mimicking pemphigus vulgaris on histologic
      examination.
AB  - We present a case of extramammary Paget's disease (EMP) on the vulva of a 77-year
      old female that on histologic examination resembled pemphigus vulgaris. The
      diagnosis of EMP was established with the help of a periodic acid-Schiff stain
      and immunophenotyping. Ultrastructural studies revealed no desmosomes between
      tumor cells and keratinocytes and only rare desmosomes between adjacent tumor
      cells. A high number of tumor cells with scant desmosomes may be the
      ultrastructural correlate with cellular discohesion in the lower epidermis and
      with the histologic resemblance to pemphigus vulgaris.

PMID- 9267742
TI  - A case of Bednar tumor. Immunohistochemical positivity for CD34.
AB  - A 42-year-old Japanese man with a Bednar tumor is described. The skin showed a
      slightly elevated, red, partially dark blue, dermal nodule growing into the deep
      subcutaneous tissue. The histological specimen showed two types of tumor cells,
      spindle-formed cells with no melanin granules and melanin-laden cells.
      Immunohistochemical stainings for CD34 and S-100 protein revealed that the former
      cells showed positivity only for CD34, while the latter were only positive for S
      100 protein. These results suggest that the Bednar tumor is a dermatofibrosarcoma
      protuberans in which melanin-laden cells coexist.

PMID- 9267743
TI  - Lamotrigine-induced Stevens-Johnson syndrome: demonstration of specific
      lymphocyte reactivity in vitro.
AB  - The novel antiepileptic drug lamotrigine (LTG) is effective as an adjunctive
      medication in partial seizures. The main adverse effects of LTG are skin
      eruptions, occurring in 3-10% of the treated patients, but these are rarely
      severe. The risk of cutaneous side effects is increased in patients receiving
      sodium valproate comedication, probably by doubling the plasma half-life of LTG
      due to competition with hepatic glucuronidation. Conversely, the risk can be
      reduced by adding LTG in a lower dose. Here, we report a patient who developed
      Stevens-Johnson syndrome (SJS) 5 weeks after adding low-dose LTG comedication to
      sodium valproate. An LTG-induced pathogenesis of the SJS was considered likely by
      a positive lymphocyte transformation test to the drug. The patient showed maximal
      peripheral blood lymphocyte reactivity to 50 micrograms LTG/ml with a stimulation
      index of 4.7 but not to nontoxic concentrations of sodium valproate. Lymphocytes
      from untreated controls neither reacted to LTG nor to sodium valproate.

PMID- 9267744
TI  - Epidermolysis bullosa pruriginosa.
AB  - Epidermolysis bullosa (EB) pruriginosa is a rare clinical subset of dystrophic
      EB, characterized by marked itching and presence of prurigo-like or lichenoid
      features. In order to further delineate the phenotype and understand the
      pathogenesis of this disorder, the clinical, histological and ultrastructural
      findings of a 19-year-old patient presenting a typical form of EB pruriginosa are
      described. The prevalence of papular itchy lichenoid lesions, signs of scratching
      and paucity of blisters at the time of clinical examination may result in
      incorrect diagnosis and treatment. Microscopic studies of the lesions show the
      typical findings of dystrophic EB associated with an unusually high density of
      collagen bundles and absence of elastic fibres in the upper dermis. Itching
      lichenoid lesions of EB pruriginosa could represent an abnormal dermal reactivity
      of some patients to their inherited bullous disorder.

PMID- 9267745
TI  - Actinic lichen planus simulating melasma.
AB  - A 23-year-old Italian woman presented with asymptomatic, symmetric,
      hyperpigmented patches on her face. The dermatosis became exacerbated in summer
      and closely resembled melasma. The histologic examination and immunofluorescence
      studies revealed typical features of lichen planus. Actinic lichen planus
      mimicking melasma is a rare dermatosis occurring mostly in women of oriental
      origin. The differential diagnosis of further facial melanoses will be discussed.

PMID- 9267746
TI  - Hypomelanosis of Ito may or may not involve hair growth.

PMID- 9267747
TI  - Mast cells in the synovium of patients with psoriasis arthropathy.

PMID- 9267748
TI  - The sound of scratching: an unusual cause of neurotic excoriations.

PMID- 9267749
TI  - Failure of cyclosporine in Netherton's syndrome.

PMID- 9267750
TI  - Long-term assessment of chronic leg ulcer treatment by autologous skin grafts.
AB  - BACKGROUND: Chronic leg ulcers (CLU) are a common and major cause of morbidity.
      For this reason, we systematically perform autologous skin grafting. OBJECTIVE:
      Long-term evaluation of this treatment. PATIENTS AND METHODS: Among the 521 out
      patients or those hospitalized for CLU between 1981 and 1993, we assessed 188
      (118 women, 70 men, mean age 74 years, 144 grafts, 44 non-grafted). RESULTS: For
      the grafted CLU, there were 46 failures (17.5%), 152 (58%) healed in a mean time
      of 2.2 months and 64 relapsed (24.5%). For the non-grafted CLU, 3 did not heal
      (3%), 20 relapsed (22.5%) and 66 healed (74.5%) in a mean time of 4.7 months. All
      the patients who suffered from painful CLU mentioned a regression of pain after
      the graft. Finally, 87.5% of patients declared that they would accept a new
      graft. CONCLUSIONS: We did not note any real difference in closure and recurrence
      rates between grafted and non-grafted ulcers. This is most likely due to an
      important selection bias related to the methodology of our study. The grafted
      ulcers were more serious: they were larger (28.9 against 7.9 cm2) and older (11.1
      against 5.6 months).

PMID- 9267751
TI  - Influence of metoclopramide on the pharmacokinetics of 8-methoxypsoralen.
AB  - BACKGROUND: Previous studies have shown important inter- and intraindividual
      variations in bioavailability of 8-methoxypsoralen (8-MOP) under the influence of
      factors that are not yet known with certainty. However, they seem to be
      independent of age, sex and concomitant retinoid administration for RePUVA
      whereas the influence of diet remains controversial. OBJECTIVE: The purpose of
      this study was to investigate a possible effect of metoclopramide on the
      bioavailability of 8-MOP since these drugs are frequently combined to prevent
      nausea, a common side effect of systemic 8-MOP. METHODS: After a standard
      breakfast and the ingestion of 8-MOP plasma kinetics of 8-MOP were assessed in 6
      healthy volunteers at 0, 1, 1.30, 1.45, 2, 2.15, 2.30, 3 and 4 h after drug
      ingestion. This procedure was repeated 3 weeks later by associating
      metoclopramide with 8-MOP. Plasma determinations of 8-MOP were performed using
      high-pressure liquid chromatography. RESULTS: Time and peak value of maximum
      plasma 8-MOP concentrations (Tmax, Cmax) ranged from 1 to 3 h and from 124 to 540
      ng/ml, respectively. Individual values of the area under the curve of time
      related 8-MOP concentration were between 284 and 1,158 ng-h/ml. Concomitant
      intake of 8-MOP with metoclopramide did not significantly influence these 3
      pharmacokinetic values. CONCLUSIONS: Our results confirm the important
      interindividual variability of the pharmacokinetics of 8-MOP. Associating 8-MOP
      with metoclopramide does not alter the pharmacokinetic values of 8-MOP and should
      not require any change in PUVA treatment.

PMID- 9267752
TI  - Impact of PUVA therapy on HIV viremia: a pilot study.
AB  - BACKGROUND: Treatment by ultraviolet radiation (UV) during human immunodeficiency
      virus (HIV) infection is controversial, since exposure of HIV-infected cells in
      vitro to UV enhances HIV replication in vitro. METHODS: Four consecutive AIDS
      patients with psoriasis and CD4 count lower than 20/mm3 were treated with 8
      methoxypsoralen and UVA (PUVA). HIV viremia expressed as long of HIV-1 RNA
      copies/ml of plasma was quantified 10 min before and 1 h following UVA exposure,
      every week during PUVA therapy and at the end of treatment. The Psoriasis Area
      Surface Index (PASI) score was used to quantify the severity of psoriasis.
      RESULTS: No significant change in HIV-1 RNA level was observed in the 18 paired
      samples analyzed before and 1 h after PUVA (median: -0.05 log HIV-1 RNA, range: 
      0.50-0.21, p = 0.10). After 12-31 UVA exposure for a total dose of 15.5-196 J/cm2
      over a period of 6-15 weeks, viremia changes from baseline in the 4 patients were
      -0.61, -0.07, 0.36 and 0.39 log HIV RNA. In 1 patient without antiviral
      treatment, a persistent decrease in viremia and transient increase in CD4 cell
      count were observed. PUVA was well tolerated and associated with significant
      improvement of the PASI score in 3 patients. CONCLUSION: HIV viremia is not
      significantly modified by PUVA therapy in AIDS patients with psoriasis.

PMID- 9267753
TI  - Steatocystoma multiplex and oligosymptomatic pachyonychia congenita of the
      Jackson-Sertoli type.
AB  - A family with affected members, previously reported to carry an R94H mutation of
      keratin K17, and characterized by a variable and oligosymptomatic form of
      pachyonychia congenita of the Jackson-Sertoli type with steatocystoma multiplex,
      is described in detail.

PMID- 9267754
TI  - Malignant atrophic papulosis.
AB  - We describe a 34-year-old woman presenting with a 1-year history of asymptomatic,
      atrophic papules disseminated mainly on the trunk. The clinical features were
      characteristic of malignant atrophic papulosis, and the histopathologic features
      were confirmatory. The etiology of this rare condition, described for the first
      time in 1941, remains unknown. Also the pathogenesis is still controversial. A
      vascular disorder has been postulated by most authors, primary inflammatory or
      thrombotic vascular changes as well as primary endothelial proliferation being
      often mentioned in the literature. In the present case, the biopsy specimen of a
      recent efflorescence showed these three alterations all together, making it
      impossible to identify conclusively the primary event. Thrombosis, being already
      noticed in such early lesions, is likely to be of pathogenic importance.
      Rheological therapy as described in the literature may therefore be the most
      appropriate. In the present case, the lesions came spontaneously to a standstill
      without drug therapy.

PMID- 9267755
TI  - Kaposi's sarcoma as manifestation of immunosuppression in organ transplant
      recipients.
AB  - We report 2 patients, negative for human immunodeficiency virus (HIV) antibodies,
      who developed generalized Kaposi's sarcoma (KS), one 5 months after renal
      transplantation while receiving cyclosporin A and prednisone, and the other 24
      months after heart transplantation while receiving cyclosporin A, azathioprine
      and prednisone. Reduction of the immunosuppressive therapy combined with
      chemotherapy and radiotherapy in both cases led to a remission of KS without
      development of transplant rejection.

PMID- 9267756
TI  - Severe, chronic anorexia and extensive leg ulcerations as presenting signs of
      primary Sjogren's syndrome.
AB  - We report the case of a 75-year-old woman with a 15-year history of inappetance
      resulting in weight loss of approximately 40 kg. On physical examination, the
      skin of the lower extremities was markedly hyperpigmented with a brown-greyish
      hue. In addition, the skin of the legs was infiltrated, erythematous, riddled
      with erosions and necrotic ulcers. Clinical and laboratory evaluation revealed
      sicca syndrome, a pronounced polyclonal hypergammaglobulinemia (60 g/l), high
      levels of antinuclear, anti-SSA and anti-SSB antibodies. Histological examination
      of involved skin demonstrated a leukocytoclastic vasculitis.

PMID- 9267757
TI  - Congenital alopecia areata.
AB  - Alopecia areata has never been documented in a newborn. Thus, it is generally
      assumed that alopecia areata is acquired only postnatally, and it is believed
      that the presence of an alopecia at birth virtually excludes its diagnosis. In
      this report we document a case of alopecia areata in a premature newborn.

PMID- 9267758
TI  - Lupus profundus/panniculitis.
AB  - A 25-year-old Caucasian woman developed two areas of tender panniculitis on her
      left thigh. While one lesion ulcerated, the other showed no overlying cutaneous
      changes. Histological examination showed lymphocytic perivascular and
      periappendageal infiltrates, and direct immunofluorescence revealed granular
      immunoglobulin deposits at the dermal-epidermal junction in the skin overlying
      the lesions. Laboratory tests revealed lymphopenia, anemia and an increased blood
      sedimentation rate. The serology for syphilis was false positive. For several
      months the patient had also been suffering from arthralgia with palpable
      synovitis of the wrist and several interphalangeal joints. Overall, these
      clinical findings are consistent with the diagnosis of lupus
      profundus/panniculitis associated with mild systemic LE.

PMID- 9267759
TI  - Control of differentiation, transformation, and apoptosis in granulosa cells by
      oncogenes, oncoviruses, and tumor suppressor genes.

PMID- 9267760
TI  - Molecular basis of thyroid hormone-dependent brain development.

PMID- 9267761
TI  - Novel insights into the molecular mechanisms of human thyrotropin action:
      structural, physiological, and therapeutic implications for the glycoprotein
      hormone family.

PMID- 9267762
TI  - Physiological action of progesterone in target tissues.

PMID- 9267763
TI  - Glucose-stimulated genes and prospects of gene therapy for type I diabetes.

PMID- 9267764
TI  - Gonadal peptides as mediators of development and functional control of the
      testis: an integrated system with hormones and local environment.

PMID- 9267766
TI  - Citation for the 1997 Ernst Oppenheimer Memorial Award of The Endocrine Society
      to Pamela L. Mellon.

PMID- 9267765
TI  - Citation for the 1997 Fred Conrad Koch Award of The Endocrine Society to Wylie
      Vale.

PMID- 9267767
TI  - Citation for the 1997 Robert H. Williams Distinguished Leadership Award of The
      Endocrine Society to Dr. Hiroo Imura.

PMID- 9267768
TI  - Citation for the 1997 Edwin B. Astwood Lecture Award of The Endocrine Society to
      John D. Baxter.

PMID- 9267769
TI  - Citation for the 1997 Gerald D. Aurbach Lecture Award of The Endocrine Society to
      Edward M. Brown.

PMID- 9267770
TI  - Citation for the 1997 Clinical Investigator Award of The Endocrine Society to
      George P. Chrousos.

PMID- 9267771
TI  - Citation for the 1997 Sidney H. Ingbar Distinguished Service Award of The
      Endocrine Society to William Rosner.

PMID- 9267772
TI  - Citation for the 1997 Richard E. Weitzman Memorial Award of The Endocrine Society
      to Donald P. McDonnell.

PMID- 9267773
TI  - Anticonvulsant effect of anterior thalamic high frequency electrical stimulation
      in the rat.
AB  - Evidence suggests that a specific subcortical pathway synaptically linking the
      anterior thalamic nuclear complex (AN) to the hypothalamus and midbrain is
      important in the expression of pentylenetetrazol (PTZ) seizures. Perturbation of
      neuronal activity along this path via focal disruption or chemical inhibition
      significantly raises seizure threshold. Recent data has demonstrated that focal
      electrical stimulation within the hypothalamic component of this pathway
      inhibited seizure expression in a current and frequency dependent fashion.
      Similar experiments were conducted in the AN to investigate the hypothesis that
      stimulation of this thalamic nuclear region can prevent the propagation of PTZ
      seizures between cortical and subcortical regions. Our results indicate that high
      frequency (100 Hz) stimulation of AN did not alter the expression of low dose PTZ
      induced cortical bursting but did raise the clonic seizure threshold compared to
      naive animals or those stimulated at sites near, but not in AN (P < 0.01). Low
      frequency stimulation (8 Hz) was in contrast, proconvulsant and could induce
      behavioral arrest responses accompanied by rhythmic high voltage EEG even without
      PTZ challenge. This data further highlights the role of AN in mediating the
      expression of seizures and provides experimental support for the concept that
      this thalamic region may be a promising target for focal stimulation to treat
      intractable seizures in humans.

PMID- 9267775
TI  - Effect of callosal bisection on seizure development and interhemispheric transfer
      effects in feline motor cortical kindling.
AB  - Motor cortical (MC) kindling was carried out in 12 adult cats, seven with the
      corpus callosum (CC) intact and five with the CC bisected, to study
      interhemispheric transfer effects and the effect of callosal bisection on both
      seizure development and interhemispheric transfer effects. MC kindling developed
      from partial motor seizures to partial onset generalized convulsions.
      Interhemispheric negative transfer effect, but not positive, existed in secondary
      site kindling and primary site retest of the CC-intact group, as shown by: (i)
      electroencephalographically lateralized seizure development in the stimulated
      hemisphere; (ii) delayed generalization of partial onset generalized convulsions;
      and (iii) a markedly unstable generalized convulsive seizure state. The CC
      bisected group showed: (i) significantly delayed seizure development from partial
      motor seizure stage to generalized convulsive seizure stage in primary and
      secondary kindling; (ii) facilitated intrahemispheric seizure development; (iii)
      the diminution of interhemispheric negative transfer effect; (iv) modified
      generalized convulsions showing extremely asymmetrical generalized convulsions
      shifting from contralaterally dominant convulsions to ipsilaterally dominant ones
      (n = 2) or alternate generalized convulsions changing from contralateral
      hemiconvulsions to ipsilateral ones (n = 3). The results obtained suggest that
      the CC plays a major role in interhemispheric seizure propagation as well as
      interhemispheric negative transfer effects in MC kindling and may have
      suppressive effect on intrahemispheric motor seizure development in MC kindling.
      However, interhemispheric seizure propagation and interhemispheric negative
      transfer effects were mediated via other structures, possibly subcortical
      structures, when the CC was bisected.

PMID- 9267774
TI  - Bradycardia induced from stimulation of the left versus right central nucleus of
      the amygdala.
AB  - Studies have demonstrated that the predominant effect of stimulation of the
      central nucleus of the amygdala is one of heart rate deceleration. Anatomical
      studies have shown that projections from the central nucleus to the
      cardioinhibitory neurons in the medulla are ipsilateral and that projections of
      the left or right vagal efferents to the heart innervate different nodal points.
      The results of this study suggest that stimulation of the central nucleus of the
      amygdala from either the left or right hemisphere produced similar increases in
      heart period. These results are discussed in terms of the effects of the
      localization of epileptic foci in the temporal lobes on the cardiovascular
      system.

PMID- 9267776
TI  - Self-reporting of everyday memory in patients with epilepsy: relation to
      neuropsychological, clinical, pathological and treatment factors.
AB  - Patients with epilepsy frequently complain of memory problems, but
      neuropsychological tests sometimes fail to detect consistent deficits; this may
      be because laboratory tests are poor indicators of everyday memory problems, or
      because subjective memory difficulties may be provoked by a variety of factors.
      To address these issues, we compared 100 patients with epilepsy and 57 healthy
      controls by means of our Questionnaire of Memory Efficiency, the State-Trait
      Anxiety Inventory, the Self-Rating Depression Scale and a battery of tests. The
      Chronbach test showed the Questionnaire of Memory Efficiency to be satisfactorily
      reliable. Patients reported significantly greater memory difficulties and higher
      levels of anxiety and depression than controls. Questionnaire of Memory
      Efficiency scores correlated with anxiety and depression levels, as well as with
      memory and learning test scores and regression analysis showed that anxiety,
      depression and visual learning had the most consistent explanatory power. No
      correlation was found with clinical variables or the presence of detectable brain
      lesion. Patients undergoing polytherapy or treatment for long periods reported
      the greatest memory difficulties. These findings suggest that subjective
      perception of memory failure reflects objective memory impairment. However,
      emotional factors and low self-esteem may bloat the reporting of everyday memory
      difficulties. The Questionnaire of Memory Efficiency seems able to provide
      information about everyday memory problems in patients with epilepsy that may be
      useful for planning neuropsychological counselling or rehabilitation.

PMID- 9267777
TI  - Serum neuron-specific enolase is a marker for neuronal damage following status
      epilepticus in the rat.
AB  - We determined the serum concentrations of neuron-specific enolase (s-NSE) in rat
      pups of 1, 2, 3, and 4 weeks of age and in adult rats that were subjected to
      lithium-pilocarpine status epilepticus (SE). Damage to brain regions was rated on
      a scale of 0 (no damage) to 5 (> 50% cell loss). Rat pups of 1-2 weeks of age had
      a higher baseline s-NSE than the adults. Following SE, 1 week old rat pups had no
      elevation of s-NSE and no histologic evidence of damage. At older ages the
      increases in NSE ranged from 18.9 +/- 0.8 ng/ml in the 2 week old (vs. 11.5 +/-
      0.5 control) to 35.8 +/- 2.1 ng/ml in the 3 week old (vs. 12.1 +/- 0.8 control).
      In the adult rats s-NSE increased from 5.4 +/- 0.4 in the control animals to 30.4
      +/- 1.3 after SE. The different brain regions examined had distinctive ontogenic
      profiles for SE-induced damage. Elevation of s-NSE after SE correlated with
      overall histologic evidence for damage.

PMID- 9267778
TI  - Scopolamine-induced convulsions in food given fasted mice: effects of
      physostigmine and MK-801.
AB  - We recently reported that scopolamine pretreated mice fasted for 48 h developed
      clonic convulsions soon after they were allowed to eat a small amount of food for
      30 s. The present experiments were performed to determine whether animals also
      develop convulsions when they were allowed to eat ad libitum and to find some
      evidence for the contribution of the cholinergic and/or glutamatergic systems in
      the underlying mechanism(s) of convulsions. Animals fasted for 48 h were treated
      with 3 mg/kg scopolamine or saline. Twenty minutes later, they were allowed to
      eat either ad libitum or a small portion of food for 30 s. Scopolamine pretreated
      animals after starting to eat ad libitum or a small amount in a restricted time
      developed convulsions in a few minutes, the incidence being 76 and 54%,
      respectively. Pretreatment of 0.17 mg/kg MK-801, the noncompetitive NMDA
      antagonist, decreased the incidence of scopolamine-induced convulsions (22%)
      without affecting latency to the onset of seizures. Pretreatment of 0.1 mg/kg
      physostigmine, the cholinesterase inhibitor, changed neither the incidence (90%)
      nor latency to the onset of scopolamine-induced convulsions.

PMID- 9267779
TI  - Biphasic effects of carbamazepine on the dopaminergic system in rat striatum and
      hippocampus.
AB  - To clarify the effects of carbamazepine (CBZ) on dopamine (DA) release and their
      metabolism, the extracellular and total levels of DA, its metabolites (DOPAC and
      HVA) and precursor, 3,4-dihydroxyphenylalanine (DOPA) in the striatum and
      hippocampus were studied. DA re-uptake and DOPA accumulation in the striatum and
      hippocampus, and monoamine oxidase (MAO) activities were also determined. After
      acute and chronic administrations of CBZ, the plasma concentration of CBZ
      associated with therapeutic activity increased the extracellular and total levels
      of all substances determined, whereas supratherapeutic concentration of CBZ
      decreased extracellular and total levels of all substances. Neither therapeutic
      nor supratherapeutic concentrations of CBZ affected MAO-A nor -B activities, nor
      DA re-uptake. DOPA accumulation caused by NSD1015 was inhibited by therapeutic
      and supratherapeutic concentrations of CBZ. These results suggest that a
      therapeutic concentration of CBZ enhances DA turnover, whereas a supratherapeutic
      concentration of CBZ inhibits DA turnover. These effects of CBZ on dopaminergic
      systems may be, at least partially, involved in the mechanisms of action of CBZ.

PMID- 9267780
TI  - Effects of non-toxic and toxic concentrations of phenytoin on monoamines levels
      in rat brain.
AB  - To clarify the mechanisms of the antiepileptic activity of phenytoin (PHI), the
      effects of PHT on extracellular and total levels of monoamines (dopamine and
      serotonin), in rat striatum and hippocampus were studied. The plasma
      concentrations of PHT associated with therapeutic activity did not affect
      striatal and hippocampal extracellular levels of monoamines, whereas
      supratherapeutic concentrations of PHT decreased striatal and hippocampal
      extracellular levels of monoamines, in a concentration dependent manner. Toxic
      concentrations of PHT produced generalized seizures 'paradoxical intoxication'
      and an initial drastic decrease in striatal and hippocampal extracellular levels
      of monoamines before seizure onset, whereas the extracellular monoamines levels
      increased after seizures. In addition, the therapeutic concentrations of PHT did
      not affect monoamine turnover, whereas supratherapeutic concentrations of PHT
      inhibited monoamine turnover. These results suggest that monoaminergic
      transmission may not be involved in the antiepileptic mechanism of action of PHT,
      and that dysfunction of monoaminergic transmission can produce generalized tonic
      clonic convulsions. Thus, the present study suggests that 'Paradoxical
      Intoxication' induced by toxic concentrations of PHT, at least partially, can be
      mediated by hypo-monoaminergic function in the brain.

PMID- 9267781
TI  - Staging prostate cancer--1997: current methods and limitations.
AB  - Clinical and pathologic staging of prostate cancer involves determination of the
      anatomic extent and burden of tumor based on the best available data. The TNM
      system [primary tumor (T), regional lymph node (N), and metastases (M)] is the
      most widely used system for prostate cancer staging. It stratifies patients
      according to the method of tumor detection, separating nonpalpable 'incidental'
      prostate cancers detected during transurethral resection for clinically benign
      prostatic hyperplasia and palpable cancers detected by digital rectal
      examination. This staging system also recognizes nonpalpable cancer detected by
      an elevated serum prostate-specific antigen level or an abnormal transrectal
      ultrasound image (stage T1c). Current staging is limited by a significant level
      of clinical understaging (up to 59% in our experience) and overstaging (up to 5%)
      based on comparison with pathologic examination of resected specimens. Proposed
      improvements in staging include preoperative systematic biopsies to assess tumor
      volume, the use of a volume-based prognostic index, and a multiple prognostic
      index. Currently, staging of prostate cancer falls short of meeting some of these
      goals, creating controversy and uncertainty about the comparative efficacy of
      various forms of therapy and expected outcomes for patients. In this report, we
      evaluate the current aspects of clinical and pathologic staging of prostate
      cancer with emphasis on the early stages in which there is the greatest chance of
      cure. Recent international agreement on the pathologic staging of prostate cancer
      should allow valid comparisons of surgical treatment from different institutions.

PMID- 9267782
TI  - Prostate cancer: indicators of aggressiveness.
AB  - In spite of the slow progression rates common to most prostate cancers, it is
      well recognized that a subset of patients will experience a more aggressive
      course with many losing their lives to this malignancy. As the number of patients
      diagnosed with prostate cancer continues to increase, there is a growing pressure
      to refine and supplement the three most important prognostic parameters for this
      disease (tumor pathologic stage, its histologic differentiation (Gleason score)
      and the level of prostate specific antigen). While this review emphasizes the
      value of these factors in stratifying patients into risk groups, it also explores
      the prognostic significance of additional commonly used and evolving non
      traditional markers (DNA ploidy, proliferation, tumor angiogenesis, and the
      status of tumor suppressor genes).

PMID- 9267783
TI  - Androgens, androgen receptors, antiandrogens and the treatment of prostate
      cancer.
AB  - Androgens play a major role in promoting the growth of the prostate gland. The
      DHT-androgen receptor complex, by association with the androgen response
      elements, specifically promotes this androgenic effect on the genome. Also
      recognized now, however, is that there is a close relationship between this
      androgen-mediated signalling pathway and those promoted by peptide growth
      factors, the crosstalk between the pathways being pivotal to growth regulatory
      control. This is discussed together with the perceived clinical potential of
      tyrosine kinase inhibitors for the treatment of prostate cancer, when the
      intracellular signalling, induced by the growth stimulatory factors, can be
      repressed.

PMID- 9267784
TI  - Neoadjuvant hormonal treatment prior to radical prostatectomy: facts and open
      questions.
AB  - Since the advent of reversible androgen deprivation, its use for a short period
      of time (usually 3 months) before radical prostatectomy has been advocated by an
      increasing number of urologists without clear and definitive proof of its
      advantage. Most authors have demonstrated downsizing of the prostate by some 30
      50%. Clinical downstaging was demonstrated in about 30% but this could not be
      confirmed at final pathological staging although downgrading was noted in some
      10% of the series analyzed. Reduction of positive margins in patients receiving
      neoadjuvant treatment varies between 15% and 25% compared to control group.
      Several biases may however complicate the analysis of these results, the main
      cause of misinterpretation being the difficulty encountered by the pathologist to
      properly grade and score the tumor after hormonal deprivation. Even if some early
      significant advantages can be observed such as a decrease of positive margins and
      anecdotal complete disappearance of tumor in some specimens, this may not
      necessarily alter the metastatic spread and the overall survival rate. Only long
      follow-up in large prospective randomized studies evaluating biological (PSA) and
      clinical failures, time to progression and survival will allow definitive
      conclusions on this still controversial approach.

PMID- 9267785
TI  - Neoadjuvant therapy prior to radiotherapy for clinically localized prostate
      cancer.
AB  - The optimal treatment for many unresectable solid tumors involves the combined
      use of chemotherapy and radiation. Retrospective and prospective randomized
      trials demonstrating a reduction in failure rates when neoadjuvant androgen
      suppression is combined with radiotherapy suggest that this is also likely to be
      true for prostate cancer. The absence of overlapping toxicities, the high
      response rates to androgen suppression, and the ease with which the prostate is
      included in radiotherapy portals makes the prostate an ideal site for
      chemoradiation. Since radiation and hormonally mediated apoptosis appear to be
      induced by different mechanisms their interaction may well be synergistic.
      Volumetric changes induced by hormonal suppression facilitate radioactive
      implantation in the prostate in men with large glands. This neoadjuvant approach
      also reduces the amount of normal tissue to be irradiated when used prior to 3
      dimensional conformal radiotherapy while allowing higher doses to the tumor. It
      may be particularly important to use antiandrogens to block the 'intraprostatic
      flare' that may result from the testosterone surge induced by luteinizing hormone
      releasing hormone in patients undergoing neoadjuvant (short course) androgen
      suppression. Men who are at particularly 'high risk' for biochemical failure when
      treated with radiotherapy alone should probably receive a 'longer' course of
      complete neoadjuvant and possibly adjuvant hormonal blockade, but the optimal
      duration and sequence of androgen suppression remain to be defined.

PMID- 9267786
TI  - Clinical assessment and management of stage T3 prostate cancer.
AB  - The early recurrence of prostate cancer originally staged as locally more than T2
      and nonmetastatic, cast doubts over the adequacy of the staging of this form of
      the disease. Monotherapy with curative intent, either by radical prostatectomy or
      radiotherapy, results in around half of the patients failing within 5 years.
      While improvements in staging of the disease are essential, the early results of
      combined modality therapy, particularly the combination of neo-adjuvant hormones
      and surgery, have been disappointing. Neo-adjuvant maximal androgen blockade
      followed by radiotherapy does appear to offer survival benefit for patients with
      locally advanced disease, and other studies combining radiotherapy adjuvant
      hormonal therapy and surgery with routine postoperative with radiotherapy are
      eagerly awaited. Combination therapy might not give the hoped-for additive
      effects of the two therapies, but almost certainly will give an increased
      incidence of complications.

PMID- 9267787
TI  - Predicting pelvic lymph node involvement in patients with localized prostate
      cancer.
AB  - Pelvic lymph node dissection is a routine staging procedure in localized prostate
      cancer. It provides prognostic information, it influences the design of the
      subsequent therapeutic strategy and it provides information necessary to compare
      the results of various therapeutic strategies. It is not considered a curative
      procedure. Thanks to improved diagnostic means, the unexpected finding of
      positive lymph nodes has decreased from 30% 15 years ago to below 10%. Hence,
      today the procedure is unnecessary in over 90% of the cases. Improvements in
      staging by imaging techniques, including CT scan, MRI, ultrasound, and ileopelvic
      scintigraphy, have so far been unsuccessful because of low specificity and
      sensitivity. Using a combination of tumor grade and stage plus serum prostate
      specific antigen (PSA) levels, a good indication of the likelihood of positive
      pelvic nodes can be obtained. A review of the literature indicates that for
      clinically localized tumors, i.e. stages T1a to T2b, lymph node dissection can be
      omitted provided serum PSA levels are < 10 ng/ml and the tumor is well to
      moderately well differentiated (Gleason grade < 7). Using these cutoff values,
      approximately 25% of our patients can be saved a pelvic lymph node dissection at
      the price of approximately 3% missed cases.

PMID- 9267788
TI  - Adjuvant therapy for prostate cancer patients at high risk of recurrence
      following radical prostatectomy.
AB  - OBJECTIVE: To identify which patients with prostate cancer are at high risk for
      local or distant recurrence after radical prostatectomy. METHODS: Review of data
      from several historical and contemporary series of patients undergoing radical
      prostatectomy. RESULTS: Patients with high-grade disease (i.e., Gleason score >
      or = 8), positive margins, and seminal vesicle invasion have relatively high
      risks of biochemical and clinical failure if no adjuvant therapy is given. Use of
      radiation therapy may improve local control rates for a subset of these patients
      (i.e., those with positive margins) but appears to have little impact on the
      later development of metastatic disease or of prostate cancer death. Hormone
      therapy may delay the onset of failure for other patients with 'high-risk'
      disease but there are few data to support its widespread use. CONCLUSIONS:
      Enhanced ability to predict which patients with high-risk prostate cancer will
      fail locally after radical prostatectomy is needed. Such patients should then be
      enrolled in a randomized study of postoperative adjuvant radiation therapy.
      Similarly, patients predicted to be at high risk for distant failure should be
      enrolled in trials evaluating conventional and 'novel' forms of hormonal therapy
      (i.e., potency sparing regimens) to determine whether such therapy delays the
      time to biochemical or clinical progression without compromising the patient's
      quality of life.

PMID- 9267789
TI  - Combined androgen blockade: the gold standard for metastatic prostate cancer.
AB  - There is no debate that both the earlier diagnosis and the treatment of men with
      cancer of the prostate (CaP) are having an impact on patients with this disease.
      In many practices there are fewer and fewer patients presenting with the classic
      diagnosis of 'advanced disease', i.e., stage M (D2). Only a few years ago, a
      large percentage of men with CaP had bony metastases when they presented to a
      physician. Hormonal ablation was the optimal treatment, and the only question was
      whether bilateral orchiectomy or medical castration should be used. The median
      time to progression with either type of monotherapy was 12-18 months, and the
      median time to survival was 24-36 months. Unfortunately, in many parts of the
      world, this scenario is still the norm. In the United States, Europe, and an
      increasing number of other countries, improved methods of detection with
      transrectal ultrasound and prostate-specific antigen (PSA) have resulted in a
      dramatic shift in the stage of disease at diagnosis. It is safe to say that in
      these countries the majority of prostate cancers are now being clinically
      diagnosed while still localized, and many organ-confined tumors are being
      definitively treated and cured. Nevertheless, many of these patients will be
      understaged at the time of diagnosis and will show progression following
      definitive therapy. In most surgical series approximately one half of patients
      will be found on pathologic examination to have pT3 disease. The use of PSA in
      the diagnosis of CaP has been mentioned, and it is being used extensively to
      monitor recurrent/residual disease. Hormonal therapy is being employed earlier in
      numerous clinical situations, and its use is no longer reserved solely for
      patients with metastatic disease. In this context combined androgen blockade has
      become the gold standard of treatment in neoadjuvant situations as well as for
      advanced CaP. Newer advances, including 3-month depot formulations of luteinizing
      hormone-releasing hormone analogues, the reversibility of medical castration, the
      preference of most patients to have medical castration, and the approval of other
      antiandrogens in the United States, all have further strengthened the use of
      combined androgen blockade. Hormonal therapy in adjuvant settings, when there is
      a high likelihood of disease recurrence, is also being used in many clinical
      situations. In addition, there appears to be a role for certain types of hormonal
      therapy in chemoprevention.

PMID- 9267791
TI  - Randomized comparison of total androgen blockade alone versus combined with
      weekly epirubicin in advanced prostate cancer.
AB  - Hormone deprivation is the gold standard for the treatment of metastatic prostate
      cancer. However, prostate cancer being primarily a heterogeneous tumor comprising
      hormone-dependent, hormone-sensitive, and hormone-insensitive cells, at least the
      latter remain unaffected by hormonal manipulations, thus making disease
      progression almost inevitable. In quest of a more comprehensive therapy we
      therefore studied the concept of early combined chemoendocrine therapy in a
      prospective randomized multicenter trial. The purpose of this study was to
      evaluate whether patients with previously untreated advanced prostate cancer
      benefit from combining total androgen blockade (TAB) with weekly epirubicin
      chemotherapy (E-TAB). From April 1988 to January 1991, 145 previously untreated
      patients with either metastatic (n = 117) or locally advanced (n = 28)
      histologically confirmed prostate cancer were randomly allocated to treatment
      with TAB by bilateral orchiectomy and flutamide 250 mg t.i.d. or TAB plus weekly
      epirubicin 25 mg/m2 i.v. for 18 weeks (E-TAB). The study endpoints were
      progression-free survival and overall survival. In addition the effects of
      treatment on quality of life were assessed by two methods. At regular intervals
      patients self-assessed ten qualities of physical, functional and emotional health
      using 5-point scales. In order to evaluate the time without disease progression
      and treatment-induced adverse effects, a modified Q-TWiST (quality-adjusted time
      without symptoms and toxicity) model was applied. At a median follow-up of 81
      months, progression-free survival and overall survival in the TAB and E-TAB
      groups were 12 and 18 months (p < 0.02) and 22 and 30 months (p = 0.12),
      respectively. In patients with > 5 sites of bone metastasis (D2max), the
      corresponding periods were 9 and 14 months (p = 0.005) and 17 and 27 months (p =
      0.06), respectively. Subjective quality of life assessment showed no impairment
      of quality of life by epirubicin treatment. Stage D and D2max patients treated
      with E-TAB had an average gain in Q-TWiST of 5 months (p = 0.098) and 8 months (p
      = 0.03), respectively, compared to the TAB treatment. Objective toxicities were
      generally mild with either treatment. In conclusion, the combination of TAB and
      epirubicin was well tolerated by patients with advanced prostate cancer and
      resulted in a significant extension of progression-free survival. This effect of
      E-TAB on objective treatment outcome was accompanied by prolonged time without
      treatment-induced adverse effects and tumor progression, i.e., time with good
      quality of life. Therefore, further studies with E-TAB appear warranted in
      patients with advanced prostate cancer.

PMID- 9267790
TI  - Innovative approaches to the hormonal treatment of advanced prostate cancer.
AB  - Androgen ablation therapy is the treatment of choice for the palliation of
      patients with advanced prostate cancer. In addition to palliation, maximal
      androgen ablation (MAA), with a combination of medical or surgical castration and
      an antiandrogen, has been shown to increase the survival of patients with
      metastatic prostate cancer in at least three large well-conducted trials. A
      subgroup analysis of these trials has suggested that patients, particularly those
      with low volumes of metastatic disease, fared much better when treated with MAA
      than with castration alone. This observation has prompted many clinicians to
      begin androgen ablation earlier in men with advanced but not necessarily
      metastatic prostate cancer, thus exposing them to prolonged periods of androgen
      ablation and its side effects. These include impotence, loss of libido, loss of
      muscle mass, malaise, and psychological disturbances. In order to offer the
      putative advantages of early hormone therapy but to mitigate its side effects a
      number of innovative methods of androgen ablation are under investigation. These
      include 'sequential androgen blockade' and 'intermittent androgen suppression'.
      Sequential androgen blockade uses a 5 alpha-reductase inhibitor to reduce the
      conversion of testosterone to dihydrotestosterone in conjunction with an
      antiandrogen or androgen-receptor blocker to prevent residual androgen from
      reaching the androgen receptor. Circulating testosterone levels are not reduced
      thus minimizing side effects. Intermittent androgen suppression uses combined
      therapy to rapidly reduce serum testosterone and induce tumor regression. From
      time to time treatment is stopped and androgen concentrations rise. This method
      reduces the total time of exposure to castrate levels of androgen and, although
      prostate-specific antigen levels rise during the second phase of therapy
      suggesting tumor growth, proponents of this cycling method suggest that this
      should prolong the time to androgen independence of the tumor. Early results with
      both methods suggest that the time to progression is long and side effects are
      minimized as compared to MAA. Large scale trials will be needed to determine the
      exact risks and benefits of these novel methods of androgen ablation.

PMID- 9267792
TI  - A comparison of perspectives on prostate cancer: analysis of utility assessments
      of patients and physicians.
AB  - BACKGROUND: Quality-of-life considerations are important in metastatic prostate
      cancer. In this study, we interviewed physicians and patients about their
      assessments and expectations on quality of life as metastatic prostate cancer
      progresses. METHODS: Physicians and patients made utility assessments of three
      hypothetical health states for metastatic disease using the time trade-off
      technique. Scores were bounded on a scale from 0.0 (death) to 1.0 (perfect
      health). RESULTS: Patients rated each of the health states as less desirable than
      the physicians. CONCLUSIONS: Physicians and patients differ in their perspectives
      on expected quality of life with metastatic prostate cancer. Our results
      emphasize the need to assess patients' utilities directly.

PMID- 9267793
TI  - Influence of blood constituents on uptake of a lipid-extracted natural surfactant
      by alveolar type II cells.
AB  - During lung injury, blood constituents may leak into the alveolar space and
      impair surfactant function. This study investigated possible interferences with
      the alveolar surfactant life cycle, by assessing the effects of various blood
      constituents on size, state of aggregation, and uptake of a natural, lipid
      extracted bovine surfactant preparation (Alveofact) into isolated rat type II
      cells in primary culture. The results showed that plasma, serum, albumin,
      immunoglobulin G, bilirubin, and galactose inhibited uptake according to
      concentration. Fibrinogen and transferrin enhanced uptake; hemoglobin,
      fibronectin, and vitronectin had no effect. Uptake was also impaired when the
      blood constituents were washed off and the surfactant was added afterward. For
      some of the blood constituents, a direct interaction with the surfactant
      liposomes was observed, resulting in changes of liposome size and state of
      aggregation. However, no correlation between these changes and effects on uptake
      were found. During lung injury with increased permeability edema, a direct
      inhibition of surfactant lipid uptake by blood constituents might lead to a
      reduced delivery of surfactant components into type II cells and disturb
      surfactant metabolism.

PMID- 9267794
TI  - Enhanced production of an EGF-like growth factor by parenchymal macrophages
      following bleomycin-induced pulmonary injury.
AB  - The secretion of molecular species related to epidermal growth factor (EGF) by
      pulmonary alveolar and parenchymal macrophages was investigated in an
      experimental model of pulmonary fibrosis in mice. Macrophages were isolated from
      cells obtained by bronchoalveolar lavage or by enzymatic disaggregation of lung
      tissue at intervals following induction of pulmonary injury by intratracheal
      injection of bleomycin. Production of EGF receptor-binding activity by these
      cells and concentrations of this activity in bronchoalveolar lavage fluid were
      measured using a radioreceptor assay. Following short-term culture under serum
      free conditions, there was significantly increased production of EGF receptor
      binding activity by parenchymal macrophages, which was demonstrable at 1 and 2
      weeks after administration of bleomycin to susceptible C57BL/6 mice. The activity
      exhibited affinity for heparin and was completely blocked by an antibody to EGF.
      There was no such increase in production of receptor-binding activity by alveolar
      macrophages or in the concentration of activity in lavage fluids. Nor was there
      any significant increase in production of EGF receptor-binding activity by
      parenchymal macrophages from bleomycin-resistant BALB/c mice. These results imply
      that selective activation of interstitial macrophages to secrete an EGF-like
      growth factor may contribute to the development of pulmonary fibrosis.

PMID- 9267795
TI  - Neutrophils pretreated with granulocyte colony-stimulating factor (G-CSF) are not
      related to the severity of endotoxin-induced lung injury.
AB  - Neutrophils play an important role in mediating acute lung injury that is
      characteristic of adult respiratory distress syndrome. Granulocyte colony
      stimulating factor (G-CSF) has been shown to increase neutrophil counts and to
      enhance their biological functions. This study investigated the effects of
      neutrophils pretreated with G-CSF on endotoxin-induced lung injury in conscious
      sheep. Nineteen sheep were chronically instrumented with a lung lymph fistula and
      vascular catheters for monitoring. Sheep were randomly allocated into three
      groups: group 1-sheep were infused only with endotoxin; group 2-G-CSF (250
      micrograms/day) was administered intravenously for 5 days prior to endotoxin; and
      group 3-G-CSF (125 micrograms) was administered just before endotoxin. In each
      group, sheep received E. coli endotoxin (1 microgram/kg) for 30 min and
      observations were made for 5 h after endotoxin administration. Circulating
      leukocyte counts before endotoxin markedly increased in group 2 and significantly
      decreased in group 3, when compared with the level in group 1 (9700 +/- 900 (SEM)
      in group 1, 49,900 +/- 10,000 in group 2, and 3600 +/- 600/microL in group 3). In
      each group, circulating leukocyte counts significantly decreased 1 h after
      endotoxin administration and then returned to baseline values. However, there
      were no significant differences in either pulmonary hemodynamic or lung lymph
      responses to endotoxin among the groups. The results indicate that G-CSF does not
      adversely affect physiologic responses of the lung to endotoxin in sheep.

PMID- 9267797
TI  - Serum-free culture of mouse tracheal epithelial cells.
AB  - Numerous investigators have described maintenance of airway epithelial cells from
      various species in a differentiated state in primary culture. Because the number
      of cells that can be isolated from the mouse trachea is very small, published
      techniques are unsuitable for this species. To examine the production of growth
      factors by murine airway epithelial cells, the authors developed a method for
      culture of mouse tracheal epithelial cells from explants, in which the population
      of cells was expanded in the presence of epidermal growth factor and insulin-like
      growth factor-I, which exhibited synergistic mitogenic activity. After
      subculture, an essentially pure population of epithelial cells was recovered,
      with a yield approximately tenfold greater than reported using protease
      dissociation of cells from the trachea. Culture of the cells at passage 2 on a
      collagen gel substratum induced differentiation toward a synthetic/secretory
      phenotype, accompanied by marked diminution in spontaneous and mitogen-induced
      DNA synthesis without loss of viability. In parallel, secretion of immunoreactive
      transforming growth factor-beta by the epithelial cells was strikingly increased,
      but could be partially down-regulated in the presence of mitogenic growth
      factors.

PMID- 9267796
TI  - Oleic acid reduces oxidant stress in cultured pulmonary artery endothelial cells.
AB  - Altering the fatty acid composition of cultured porcine pulmonary artery
      endothelial cells (PAEC) modulates their susceptibility to oxidant stress. This
      study demonstrates that supplementing PAEC with oleic acid (18:1 omega 9), but
      not gamma-linolenic acid (18:3 omega 6), provided dose-dependent protection from
      hydrogen peroxide (H2O2)-induced cytotoxicity. It was hypothesized that 18:1
      reduced PAEC susceptibility to oxidant stress by altering H2O2 metabolism. To
      test this hypothesis, confluent PAEC monolayers were treated with 100-200 microM
      H2O2 or control conditions 24 h after supplementation with 0.1 mM 18:1, 18:3, or
      vehicle for 3 h. Intracellular [H2O2] in control cells (14.4-29.0 pM), estimated
      from the rate of aminotriazole-mediated inactivation of endogenous catalase
      activity, increased following treatment with 200 microM H2O2 (19.0-37.3 pM).
      Supplementation with 18:1 attenuated increases in intracellular [H2O2] only in
      oxidant-exposed cells, whereas supplementation with 18:3 attenuated intracellular
      [H2O2] only in control cells. Supplementation with 18:1 or 18:3 tended to reduce
      or enhance PAEC lipid hydroperoxide content following H2O2 exposure,
      respectively, but did not alter PAEC reduced glutathione content, the activities
      of glutathione peroxidase or catalase, or H2O2 uptake and release. Alteration of
      H2O2 metabolism in cultured PAEC may contribute to the ability of fatty acids to
      modulate cellular oxidant susceptibility.

PMID- 9267798
TI  - Pulmonary vagal reflexes and breathing pattern are not altered in elastase
      induced emphysema in rats.
AB  - The role of nonmyelinated and myelinated vagal afferents in pulmonary reflexes
      and breathing pattern was examined in elastase-treated emphysemic rats. Fourteen
      to 17 days after intratracheal instillation of 1 IU/gm of porcine pancreatic
      elastase or 0.5 mL of saline, elastase-treated rats had a decreased alveolar
      surface area to volume of parenchyma (Sv) (42.44 +/- 1.7 vs. 31.51 +/- 1.1
      mm2/mm3), increased quasistatic compliance (QSC) (1.05 +/- 0.06 vs. 1.25 +/- 0.09
      mL/cm H2O), functional residual capacity (FRC) (4.31 +/- 0.10 vs. 5.88 +/- 0.37
      mL), residual volume (RV) (3.02 +/- 0.14 vs. 4.27 +/- 0.31 mL), and total lung
      capacity (TLC) (14.04 +/- 0.28 vs. 15.58 +/- 0.54 mL). There were no changes in
      the strength of the pulmonary chemoreflex, the strength of the Hering-Breuer
      inflation reflex, or breathing pattern before or after vagal perineural capsaicin
      treatment (VPCT) or vagotomy. There were, however, significant negative
      correlations between Sv and TLC, FRC and RV, and a near significant (p < .09)
      negative correlation between Sv and QSC, but no significant correlations between
      Sv and indices of either the pulmonary chemoreflex or Hering-Breuer inflation
      reflex. The results indicate that pulmonary vagal nonmyelinated and myelinated
      reflex activity and breathing pattern are not affected by elastase-induced
      emphysema in rats.

PMID- 9267799
TI  - Pulmonary veins and bronchial vessels undergo remodeling in sustained pulmonary
      hypertension induced by continuous air embolization into sheep.
AB  - While it is well known that chronic pulmonary hypertension is accompanied by
      characteristic structural changes in the pulmonary arteries, it is becoming
      increasingly apparent that the remodeling process also involves the venous side
      of the circulation. The present paper utilizes a sheep model of sustained
      pulmonary hypertension induced by continuous air embolization (CAE) into the
      pulmonary arterial circulation to examine the structure of the pulmonary veins
      and bronchial vasculature. Morphometric techniques were applied to the pulmonary
      veins and bronchial vessels following distension of the venous circulation with a
      barium-sulfate gelatin mixture; this route of filling also resulted in distension
      of the bronchial vessels. Four and 12 days of CAE resulted in a significant
      increase in the proportion of muscular pulmonary veins (e.g., percent muscular
      veins < 75 microns following 12 days CAE = 17.7 +/- 6.9; controls = 0), an
      approximate doubling in percent venous medial thickness, and a 50% reduction in
      number of barium-filled peripheral vessels. Examination of the bronchial
      circulation revealed a striking increase in volume due both to a 50% increase in
      vessel diameter and a threefold increase in number of small vessels (p < .05).
      The authors conclude that CAE-induced chronic pulmonary hypertension is
      associated with remodeling of both the pulmonary veins and bronchial circulation
      as well as the pulmonary arteries. The mechanisms for these structural
      alterations are not certain, but may include local release of vasoactive and
      inflammatory mediators and an increase in bronchopulmonary anastomoses.

PMID- 9267800
TI  - Rare disease genes--lessons and challenges.

PMID- 9267801
TI  - Small open reading frames: beautiful needles in the haystack.

PMID- 9267802
TI  - Recombination hot spots and human disease.

PMID- 9267803
TI  - A high-resolution physical and transcript map of the Cri du chat region of human
      chromosome 5p.
AB  - A high-resolution physical and transcription map has been generated of a 3.5-Mb
      region of 5p15.2 that is associated with the Cri du chat (CDC) syndrome.
      Utilizing a variety of resources including a natural deletion panel, a chromosome
      specific radiation hybrid panel, and YAC, PAC, and BAC genomic clones we have
      ordered > 60 STSs within this region. Approximately 45% of these STSs were
      obtained from publicly available whole genome maps, thus allowing for integration
      of this map with currently available resources. Thirteen of these markers were
      ESTs. In addition, > 70 exon trapped products have been mapped on the natural
      deletion panel and bacterial clone resource. The combination of these resources
      has allowed for the identification of 17 transcripts within this region, all of
      which represent candidate genes for CDC. Further characterization of the genomic
      contig also revealed that this region of 5p15 contains a large number of
      repetitive elements.

PMID- 9267804
TI  - Multiplex sequencing of 1.5 Mb of the Mycobacterium leprae genome.
AB  - The nucleotide sequence of 1.5 Mb of genomic DNA from Mycobacterium leprae was
      determined using computer-assisted multiplex sequencing technology. This brings
      the 2.8-Mb M. leprae genome sequence to approximately 66% completion. The
      sequences, derived from 43 recombinant cosmids, contain 1046 putative protein
      coding genes, 44 repetitive regions, 3 tRNAs, and 15 tRNAs. The gene density of
      one per 1.4 kb is slightly lower than that of Mycoplasma (1.2 kb). Of the protein
      coding genes, 44% have significant matches to genes with well-defined functions.
      Comparison of 1157 M. leprae and 1564 Mycobacterium tuberculosis proteins shows a
      complex mosaic of homologous genomic blocks with up to 22 adjacent proteins in
      conserved map order. Matches to known enzymatic, antigenic, membrane, cell wall,
      cell division, multidrug resistance, and virulence proteins suggest therapeutic
      and vaccine targets. Unusual features of the M. leprae genome include large
      polyketide synthase (pks) operons, inteins, and highly fragmented pseudogenes.

PMID- 9267805
TI  - High-resolution physical and transcriptional mapping of the autoimmune
      polyendocrinopathy-candidiasis-ectodermal dystrophy locus on chromosome 21q22.3
      by FISH.
AB  - Autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, PGD type
      I) is an autosomal recessive disease enriched in the Finnish population.
      Previously, we have assigned APECED to a 2.6-cM interval on chromosome 21q22.3 by
      linkage analysis in 14 Finnish families. This subtelomeric region of 21q22.3
      seems to have sequence features resulting in its under-representation in large
      insert genomic libraries, and only a few large insert clones have been available
      for positional cloning to date. Here, we report the refined localization of the
      APECED gene and a visual physical map of 800 kb covering the critical chromosomal
      region for the gene. In the construction of the physical map, the recently
      developed fiber FISH techniques were essential for the orientation of the cosmid
      PI, PAC, and BAC clones in relation to each other. We also localized two cDNAs
      within this genomic region by fiber FISH combined with the highly sensitive
      tyramide-based detection method. These data will facilitate the final cloning of
      the APECED gene and any other novel gene in this complex genomic region.

PMID- 9267806
TI  - A locus for autosomal recessive pseudoxanthoma elasticum, with penetrance of
      vascular symptoms in carriers, maps to chromosome 16p13.1.
AB  - Pseudoxanthoma elasticum (PXE) is a heritable systemic disorder characterized by
      calcification of the elastic fibers of the connective tissue. Symptoms are
      predominantly noted in the eye, the skin, and the cardiovascular system,
      resulting in visual loss, skin lesions, and life-threatening vascular disease. In
      the study we combined homozygosity mapping and genome scanning with 374 markers
      in affected individuals from a PXE family from a genetically isolated population
      in The Netherlands. Initial homozygosity in two or three patients was found with
      up to 20 markers, among which D16S292 located in 16p13.1. Upon refined and more
      extensive family screening of the latter region, close linkage without
      recombination was found with the marker D16S764 (Zmax = 6.27). Despite clear
      autosomal recessive inheritance of the ocular symptoms in PXE, vascular symptoms
      appear in 40%-50% of the heterozygotes.

PMID- 9267807
TI  - A 3-Mb contig from D11S987 to MLK3, a gene-rich region in 11q13.
AB  - We have combined genetic, radiation-reduced somatic cell hybrid (RRH),
      fluorescent in situ hybridization (FISH), and physical mapping methods to
      generate a contig of overlapping YAC, PAC, and cosmid clones corresponding to > 3
      continuous Mb in 11q13. A total of 15 STSs [7 genes (GSTP1, ACTN, PC, MLK3, FRA1,
      SEA, HNP36), 4 polymorphic loci (D11S807, D11S987, GSTP1, D11S913), 3 ESTs
      (D11S1956E, D11S951E, and W1-12191), and 1 anonymous STS (D11S703)], mapping to
      three independent RRH segregation groups, identified 26 YAC, 7 PAC, and 16 cosmid
      clones from the CGM, Roswell Park, CEPH Mark I, and CEPH MegaYAC YAC libraries, a
      5 genome equivalent PAC library, and a chromosome II-specific cosmid library.
      Thirty-six Alu-PCR products derived from 10 anonymous bacteriophage lambda
      clones, a cosmid containing the polymorphic marker D11S460, or STS-positive YAC
      or cosmid clones were identified and used to screen selected libraries by
      hybridization, resulting in the identification of 19 additional clones. The
      integrity and relative position of a subset of clones was confirmed by FISH and
      were found to be consistent with the physical and RRH mapping results. The
      combination of STS and Alu-PCR-based approaches has proven to be successful in
      attaining contiguous cloned coverage in this very GC-rich region, thereby
      establishing for the first time the absolute order and distance between the
      markers: CEN-MLK3-(D11S1956E/D11S951E/W1-12191)-FRA1-D 11S460-SEA-HNP36/ D11S913
      ACTN-PC-D11S703-GSTP1-D11S987-TEL.

PMID- 9267809
TI  - Apoptosis: gene-directed cell death. An overview.
AB  - Apoptosis, a term derived from the ancient Greek meaning a 'falling off, such as
      'of leaves from a tree', is a physiologic cell death used by the body to delete
      unwanted cells without eliciting an immune response or inflammatory reaction. A
      hallmark of apoptosis is the activation of endonuclease that attacks the cell's
      genomic DNA at the linker regions that connect the nucleosomal units. Degradation
      of DNA produces DNA fragments in size multiples of 185 to 200 bp that can be
      observed as a distinct 'DNA ladder pattern'. Apoptotic cell death is gene
      directed cell death.

PMID- 9267808
TI  - Fidelity and mutational spectrum of Pfu DNA polymerase on a human mitochondrial
      DNA sequence.
AB  - The study of rare genetic changes in human tissues requires specialized
      techniques. Point mutations at fractions at or below 10(-6) must be observed to
      discover even the most prominent features of the point mutational spectrum. PCR
      permits the increase in number of mutant copies but does so at the expense of
      creating many additional mutations or "PCR noise". Thus, each DNA sequence
      studied must be characterized with regard to the DNA polymerase and conditions
      used to avoid interpreting a PCR-generated mutation as one arising in human
      tissue. The thermostable DNA polymerase derived from Pyrococcus furiosus
      designated Pfu has the highest fidelity of any DNA thermostable polymerase
      studied to date, and this property recommends it for analyses of tissue
      mutational spectra. Here, we apply constant denaturant capillary electrophoresis
      (CDCE) to separate and isolate the products of DNA amplification. This new
      strategy permitted direct enumeration and identification of point mutations
      created by Pfu DNA polymerase in a 96-bp low melting domain of a human
      mitochondrial sequence despite the very low mutant fractions generated in the PCR
      process. This sequence, containing part of the tRNA glycine and NADH
      dehydrogenase subunit 3 genes, is the target of our studies of mitochondrial
      mutagenesis in human cells and tissues. Incorrectly synthesized sequences were
      separated from the wild type as mutant/wild-type heteroduplexes by sequential
      enrichment on CDCE. An artificially constructed mutant was used as an internal
      standard to permit calculation of the mutant fraction. Our study found that the
      average error rate (mutations per base pair duplication) of Pfu was 6.5 x 10(-7),
      and five of its more frequent mutations (hot spots) consisted of three
      transversions (GC-->TA, AT-->TA, and AT-->CG), one transition (AT-->GC), and one
      1-bp deletion (in an AAAAAA sequence). To achieve an even higher sensitivity, the
      amount of Pfu-induced mutants must be reduced.

PMID- 9267810
TI  - Analysis of relationship between programmed cell death and cell cycle in limb
      bud.
AB  - Programmed cell death plays a crucial role in limb morphogenesis of amniote. In
      this paper, we showed that cell cycle and cell death in limb-buds were closely
      related events and there existed a critical S-phase, which corresponded to the
      most sensitive time for inhibition of cell death following administration of an
      excess dose of 5-bromodeoxyuridine (BrdU). The use of microfluorometry of BrdU
      incorporation coupled with measurement of DNA amount of individual cells enabled
      us to consider that cells committed to die were withdrawn from cell cycle at G2
      phase. Finally, we will summarize the nuclear events involved in apoptosis in
      limb morphogenesis in relation to cell cycle.

PMID- 9267811
TI  - Expression of Fas-Fas ligand system associated with atresia through apoptosis in
      murine ovary.
AB  - We examined the contribution of Fas and its ligand (FasL) in the process of
      follicular atresia using murine intraovarian follicles and pregnant mare's serum
      gonadotropin (PMSG)-hyperovulated eggs. Reverse transcriptase/polymerase chain
      reaction-Southern blot hybridization demonstrated positive expression of Fas in
      both intraovarian oocytes and hyperovulated eggs. In contrast, expression of FasL
      was only detected in granulosa cells. These findings were histologically
      confirmed by in situ hybridization using Fas- and FasL-specific probes. A time
      course study showed that Fas mRNA was positive in atretic follicles through day 0
      and day 2 of PMSG stimulation and negative thereafter. Levels of FasL mRNA were
      the highest on day 1 and tapered off toward day 5 of PMSG stimulation. Levels of
      elongation factor 1 alpha mRNA, a constitutive element, were constantly
      maintained throughout the experimental period. Coculture of ovulated eggs, intact
      and zona-free, and granulosa cells demonstrated positive TUNEL staining only in
      zona-free eggs. These findings indicate that follicular atresia is caused by
      apoptosis, and the apoptosis associated with internucleosomal DNA fragmentation
      is directly regulated by the Fas/FasL system.

PMID- 9267812
TI  - Does apoptosis contribute follicular atresia and luteal regression in human
      ovary?
AB  - We investigated apoptosis in 37 human ovaries from normally cycling women to
      determine the mechanism of the various stages of follicular atresia and the
      regression of corpus luteum in human. Apoptosis was examined by 3'-hydroxy nick
      end-labeling, by immunostaining of an apoptosis-related antigen, Le(y) and by
      cell death-related genes, bcl-2. Immunoreactivity for Le(y) and nick end-labeling
      reactive cells were not observed in the follicular and luteal phases, except for
      scattered cells in the degenerating corpus luteum. On the other hand,
      immunoreactivity for bcl-2 was observed in the granulosa cells of antral
      follicles. These results indicated that apoptosis is not obvious through
      follicular maturation and luteal regression. This may be due to the relatively
      long process of human follicular growth and atresia.

PMID- 9267813
TI  - Apoptosis of human ovary and uterine endometrium during the menstrual cycle.
AB  - To investigate apoptotic changes in the ovary or uterine endometrium, we studied
      the cleavage of DNA in these tissues obtained from regularly cycling women by in
      situ analysis of DNA integrity and quantitative end labeling of DNA gel
      fractionation. In situ analysis of several sized atretic follicles of ovaries
      revealed that granulosa cells showed positive staining to some extent, however,
      these methods do not discriminate between cells undergoing apoptosis and those
      undergoing necrosis. Total DNA extracted from human corpora lutea (CL) of the
      early luteal phase contained predominantly high molecular weight DNA, whereas CL
      of the midluteal phase exhibited the appearance of DNA cleavage into low
      molecular weight ladders characteristic of apoptosis. Although apoptotic DNA
      cleavage of human CL increased from the midluteal phase to the late luteal phase,
      CL of early pregnancy did not exhibit apoptotic DNA fragmentation. Both large and
      small luteal cells were the primary cell type exhibiting DNA cleavage in human CL
      of the midluteal and late luteal phases and in regressive CL. Biochemical
      analysis of human endometrium revealed that the ladder pattern cleavage of DNA
      was identified at three different phases of the menstrual cycle, namely the early
      proliferative, late secretory, and menstrual phases. Cells undergoing apoptosis
      were scattered in the functional layer of the early proliferative endometrium,
      but not in the late proliferative phase to midsecretory phase: At the beginning
      of the late secretory phase, apoptosis reappeared in the stromal cells and spread
      gradually to almost all components of the functional layer. By contrast, cells in
      the basal layer showed no evidence of apoptosis throughout the menstrual cycle.
      The present findings suggest that: (1) human luteal regression may be mediated by
      apoptosis; (2) CL of early pregnancy may be rescued from luteolysis through
      inhibition of the occurrence of apoptotic luteal cell death, and (3) apoptosis
      occurs in specific populations of endometrial cells during the human endometrial
      cycle. In conclusion, apoptosis might play an important role in the regulation of
      the menstrual cycle in women.

PMID- 9267814
TI  - Effect of luteinizing hormone-releasing hormone analogs on the rat ovarian
      follicle development.
AB  - Our objective was to study the direct action of luteinizing hormone-releasing
      hormone (LHRH) agonist buserelin and LHRH antagonist Cetrorelix (SB-75) on cell
      proliferation and differentiation in the rat ovarian follicle. Preovulatory
      follicles were isolated from PMSG-primed immature rats and incubated in the
      presence or absence of hCG (10 IU/ml), buserelin (10(-9)-10(-6) M) or Cetrorelix
      (10(-9)-10(-6) M) for 12 h in vitro. Buserelin induced meiotic maturation of the
      follicle-enclosed oocytes dose-dependently. The percentage of oocytes with
      germinal vesicle breakdown at 10(-6) M buserelin (73.3%) did not differ from that
      of hCG-treated control (73.3%). Buserelin also significantly stimulated
      prostaglandin E2 and progesterone production by follicles, but not estradiol
      production. Granulosa cells were obtained from the preovulatory follicles and
      cultured for 5 days. Epidermal growth factor (EGF) stimulated granulosa cell
      growth at concentrations of 1, 10 and 100 ng/ml. In contrast, both buserelin and
      Cetrorelix inhibited granulosa cell growth dose-dependently in the range of 10(
      10)-10(-5) M, with Cetrorelix inducing a greater growth inhibition than
      buserelin. Electrophoretic analysis of genomic DNA extracted from granulosa cells
      treated with 10(-6) M concentration of either LHRH analog revealed a definitive
      ladder pattern of oligonucleosomal length DNA fragments characteristic of
      apoptosis. Western blotting detected that EGF-induced tyrosine phosphorylation
      was not affected by either analog. These results demonstrate that LHRH agonist
      and antagonist inhibit directly proliferation of granulosa cells through
      apoptosis, without interference with EGF receptor phosphorylation, whereas LHRH
      agonist stimulates cell differentiation in the preovulatory follicle.

PMID- 9267815
TI  - Apoptosis in human endometrial and endometriotic tissues.
AB  - Apoptosis has recently been proposed to represent programmed cell death. Several
      investigations have revealed that uterine endometrium in mammals can be regulated
      by apoptosis. However, apoptosis may be less likely to occur in human eutopic
      endometrium. On the other hand, immunoreactivity of Bcl-2 that may serve a
      regulatory function in protecting from undergoing apoptosis was observed in
      uterine endometrial glandular cells in the proliferative phase through to the
      early secretory phase. In endometriotic tissues, although apoptosis was detected
      in all the samples from ovarian endometriosis, it was indicated in only a few
      tissues from adenomyosis. Bcl-2 was negative in almost all samples from ovarian
      endometriosis, whereas it was positive in all adenomyotic tissues from cases in
      the proliferative phase, but in none of tissues from cases in the secretory
      phase. Thus, ovarian endometriosis can be discriminated from adenomyosis based on
      the existence of apoptosis though both represent a type of ectopic endometrial
      tissue, and the pathogenesis or condition of the cells may be different between
      ovarian endometriosis and adenomyosis.

PMID- 9267816
TI  - Ploidy determination on histologic sections of breast cancer specimens by image
      analysis using mathematical correction algorithms.
AB  - Several mathematical correction algorithms were developed to solve the problem of
      the unavoidable measurement of fragmented nuclei when determining DNA ploidy on
      thin histologic slides. These algorithms were designed for model tissue and until
      now had not been tested thoroughly on malignant human tissue. We evaluated the
      use of mathematical correction algorithms applied to measurements on thin
      histologic sections of breast cancer specimens, with strict control of the
      section thickness. Fifteen cases of breast carcinoma with known ploidy (5
      diploid, 5 tetraploid, and 5 aneuploid breast cancer samples) were included. From
      each tissue block, we made a single-cell preparation and cut a thin histologic
      section. We evaluated the thickness of each of these sections according to a
      recently developed protocol and included only sections with a thickness between 5
      and 6 microns. We performed DNA measurements with a custom-made image analyzing
      system equipped with a 100x oil immersion objective. Histograms of tissue section
      measurements were corrected according to the algorithms of McCready and
      Papadimitriou and of Haroske et al. We compared these results with the
      uncorrected histograms and with the histograms of the single-cell preparations.
      We also measured the single-cell preparations with a commercially available high
      resolution image cytometer. The correlation between both image cytometers used
      was high (r = 0.99). Histogram correction improved results of tissue section
      measurements in all of the nondiploid tumors when compared with the uncorrected
      histograms. There were no significant differences between the correction
      algorithms used (correlation to the single-cell measurements determined by a
      linear regression; r = 0.98 for both algorithms). No overcorrection of the
      histograms occurred. We conclude that reliable DNA tissue section measurements
      are possible on breast cancer specimens and that such measurements will
      contribute to our understanding of tumor cell kinetics in small tumor cell
      populations not detected in single-cell measurements.

PMID- 9267817
TI  - Prognostic value of DNA ploidy using flow cytometry in 1301 breast cancer
      patients: results of the prospective Multicenter Morphometric Mammary Carcinoma
      Project.
AB  - The literature on breast cancer reports conflicting prognostic results with
      respect to DNA ploidy of flow cytometric DNA histograms. This might result from
      different DNA ploidy classification methods. Our study evaluated the prognostic
      power of DNA ploidy, using different classification methods, in a large
      prospective group (n = 1301) of breast cancer patients. Flow cytometric DNA
      histograms obtained from fresh frozen material were interpreted with use of a
      commercially available computer program. On the basis of the number of stemlines
      and the DNA Index, we classified the DNA ploidy by different methods. In all of
      the cases, the classification method "DNA diploid versus DNA nondiploid" provided
      the best prognostic significance for overall survival (OS) (Mantel-Cox (MC) =
      5.4, P = .02; relative risk (RR) = 1.3, P = .05) and for disease-free survival
      (DFS) (MC = 11.8, P = .0006; RR = 1.3, P < .05). This was also true for the OS of
      the lymph node-positive (but not the lymph node-negative) subgroup (MC = 4.1, P =
      .04; RR = 1.3, P = .05). In subgroups classified on the basis of tumor size, DNA
      ploidy showed prognostic significance for DFS only in the subgroup of tumors
      smaller than 2 cm and larger than 5 cm. In multivariate analysis, DNA ploidy
      showed no additional prognostic power to lymph node status and tumor size. The
      classification "DNA diploid versus DNA nondiploid" was mostly consistent with
      respect to prognostic power for OS and DFS, especially in small or lymph node
      positive tumors. The RR of DNA nondiploid patients was only marginally higher,
      however, so large study groups are required to reach statistical significance.
      This could partly explain the disagreements in the literature. Therefore, DNA
      ploidy seems to be of little clinical importance in breast cancer patients,
      compared with other prognostic parameters.

PMID- 9267818
TI  - Comparison of quantitative and semiquantitative methods of assessing MIB-1 with
      the S-phase fraction in breast carcinoma.
AB  - Different methods of assessing cell proliferation in breast cancer are currently
      being evaluated. Inherent qualities are required for such methods to be used on a
      routine basis in a pathology laboratory. Such qualities include high sensitivity
      and specificity in recognizing proliferating cells, simplicity in execution, and
      reproducibility. The MIB-1 antibody permits the immunohistochemical detection of
      the Ki67 antigen in fixed and paraffin-embedded tissue sections. The aim of our
      study was to compare a semiquantitative and quantitative method of assessing MIB
      1 immunostaining with the S-phase fraction (SPF) determined by flow cytometry in
      a series of 112 breast carcinomas. The median semiquantitative MIB-1 score (SQ
      MIB-1) in our series was 27.5%. The median quantitative MIB-1 score (B.MIB-1) was
      563 positive neoplastic cells per square millimeter of tumor, and, when corrected
      by the volume percentage nuclei (C.MIB-1), 2844 positive nuclei per square
      millimeter of total nuclear area. These three indices were strongly correlated to
      the SPF (r = 0.73, 0.72, 0.72, n = 78), respectively for SQ.MIB-1, B.MIB-1, and
      C.MIB-1, MIB-1, assessed quantitatively or semiquantitatively, correlated with
      the Scarff, Bloom, and Richardson grade, including the mitotic index and nuclear
      grade, as well as with the progesterone receptor status. SQ.MIB-1 determination
      was easier and faster than B.MIB-1 and C.MIB-1 determination. A high correlation
      was found for SQ.MIB-1 results between two observers in this series (r = 0.92, n
      = 112), but the SQ.MIB-1 repeatability coefficient was 17.6%. Semiquantitation of
      MIB-1 is strongly correlated to the SPF and is an easy and rapid method of
      assessing cell proliferation. More studies are necessary for additional
      assessment of its reproducibility and its prognostic value in breast cancer.

PMID- 9267819
TI  - Schwannomas of the sinonasal tract and nasopharynx.
AB  - Approximately 45% of benign peripheral nerve sheath tumors occur in the head and
      neck region. Of these, schwannomas (neurilemomas) arising from the nasal cavity
      and paranasal sinuses account for less than 4%. Pathologic features of this
      subset are not well documented. We report a series of five cases of sinonasal
      schwannoma and one in the nasopharynx. The male-to-female ratio was equal, and
      the age at presentation ranged from 38 to 65 years of age (median, 52 yr). Four
      of the lesions were located within the nasal cavity, one arose from the maxillary
      sinus, and one originated in the nasopharynx, with extension into the Eustachian
      tube. Two cases showed local bony destruction, with intracranial extension.
      Presenting clinical symptoms included nasal obstruction, epistaxis, rhinorrhea,
      anosmia, facial swelling, headache, and serous otitis media; the two cases with
      intracranial spread also presented with visual disturbances. All of the six cases
      were treated by surgical excision. Clinical follow-up in five cases ranged from 6
      to 48 months (median, 27 mo). Histologically, all of the lesions shared many
      cytomorphologic features common to schwannomas arising at other sites, and all of
      the six cases showed strong, diffuse immunoreactivity for S-100 protein. Four
      cases showed features of the cellular variant, and one showed focal granular cell
      change. An unusual and previously poorly documented histologic feature, distinct
      from schwannomas arising at most other anatomic sites, was a lack of
      encapsulation, which, when combined with hypercellularity, often raised suspicion
      of malignancy. Because none of the cases in this series has shown either local
      recurrence or postoperative metastasis to date, lack of encapsulation and locally
      destructive growth in an otherwise histologically typical schwannoma arising at
      this site should not suggest malignant potential.

PMID- 9267820
TI  - MDM-2 oncoprotein overexpression in laryngeal squamous cell carcinoma:
      association with wild-type p53 accumulation.
AB  - The MDM-2 gene encodes for a nuclear phosphoprotein that binds p53 and inhibits
      its ability to activate transcription by concealing the p53 activation domain. It
      has been suggested that MDM-2 overexpression might represent an alternative
      mechanism by which p53-mediated pathways are inactivated in human tumors. MDM-2
      overexpression can be detected by immunohistochemical analysis as a result of
      gene amplification and/or increased mRNA expression. We studied MDM-2 gene
      amplification and protein overexpression in 46 and 50 cases, respectively, of
      laryngeal squamous cell carcinomas previously analyzed for p53 gene alterations.
      Not one of the cases showed MDM-2 gene amplification, whereas MDM-2 nuclear
      immunoreactivity was found in 17 tumors (34%). In 10 of these, coexpression of
      p53 protein was detectable in the absence of gene mutations in exons 5 through 9
      (P = .03). Likewise, MDM-2 was also overexpressed in 18 (46%) of 39
      morphologically normal mucosa samples, 15 (50%) of 30 preneoplastic lesions, and
      9 (40%) of 22 cases of severe dysplasia. Finally, we found no significant
      correlations between MDM-2 expression (neither per se nor in association with
      wild-type or mutated p53), and the evaluated clinicopathologic parameters of
      histologic grade, lymph node status, or clinical stage. Our results suggest that
      MDM-2 gene amplification might not occur in laryngeal carcinomas and that MDM-2
      protein overexpression might represent an alternative mechanism by which p53 is
      inactivated in the early stages of laryngeal cancer tumorigenesis.

PMID- 9267821
TI  - Liver biopsy in neonatal cholestasis: a review on statistical grounds.
AB  - The aim of this study was to improve the accuracy of the histopathologic
      diagnosis in the differential diagnosis between obstructive and nonobstructive
      forms of neonatal cholestasis, using this clinical situation as a model for a
      mathematical approach. The study was blind, and we performed it in two steps. In
      the first step, 49 histologic parameters were visually estimated and were scored
      on a scale of 0 to 4+ in 100 liver biopsy specimens obtained between 1980 and
      1985 from 78 patients with neonatal cholestasis. Forty-eight of these 100
      specimens were from patients with final diagnosis of obstructive cholestasis
      (Group I), and 52 were from patients with nonobstructive cholestasis (Group II).
      The age range was 3 to 24 weeks (median, 12.5 wk). Twelve histologic variables
      were selected by chi 2 and Fisher's exact test (P < .05). Next, a series of
      combinations among these variables were submitted to statistical analysis by
      logistic regression method, defining a six-variable model that had the most
      powerful predictive value to classify the type of cholestasis. The variables were
      portal ductal proliferation, bile plugs in portal bile ductules, portoportal
      bridges, neutrophils, hepatocyte swelling, and multinucleated giant hepatocytes.
      The score obtained by this model correspond to the probability of a case
      belonging to Group I. The accuracy, sensitivity, and specificity rates were
      94.0%. In the second step, the model was applied to a new sample of 74 needle
      liver biopsy specimens obtained between 1990 and 1995, 45 from patients in Group
      I and 29 from patients in Group II. The age range was 3 to 15 weeks (median, 8
      wk). The accuracy, sensitivity, and specificity rates were 90.5%, 100%, and
      75.9%, respectively. In our diagnostic routine, this score has been
      systematically reported and has been helpful in orienting the therapeutic
      decision in this group of patients.

PMID- 9267822
TI  - Mediastinal yolk sac tumors associated with prominent multilocular cystic changes
      of thymic epithelium: a clinicopathologic and immunohistochemical study of five
      cases.
AB  - Five cases of yolk sac tumor of the anterior mediastinum associated with
      prominent thymic cystic changes are presented. The patients were five men between
      the ages of 17 and 22 years (mean, 19.5 yr). Clinically, four patients presented
      with symptoms of chest pain and shortness of breath, whereas the fifth was
      asymptomatic: his tumor was discovered during a routine physical examination.
      None of the patients had a history of previous tumor elsewhere. Grossly, the
      tumors were described as cystic lesions measuring between 8 and 12 cm in greatest
      dimension. Histologically, the tumors showed prominent cystic changes reminiscent
      of those observed in acquired multilocular thymic cysts, i.e., the presence of
      cystic cavities lined by squamous epithelium with prominent inflammatory changes,
      lymphoid hyperplasia, cholesterol cleft granulomas, and remnants of thymic tissue
      in the walls of the cysts. In addition, there was a neoplastic cellular
      proliferation composed of small cells with scant cytoplasm, round nuclei, and
      inconspicuous nucleoli adopting a reticular pattern of growth and, in some areas,
      embedded in abundant myxoid stroma. Numerous intra- and extracellular hyaline
      globules, as well as Schiller-Duval bodies, could also be identified.
      Immunohistochemical studies showed positive reaction with alpha-fetoprotein
      antibodies in the tumor cells. Follow-up information obtained in these patients
      showed that all had died of tumor 1 to 3 years after initial diagnosis. The
      present cases document another unusual but distinctive growth pattern of yolk sac
      tumor in the mediastinum and highlight the importance of proper sampling of
      cystic lesions in this location.

PMID- 9267823
TI  - Prognostic implications of extracapsular extension of lymph node metastases in
      prostate cancer.
AB  - We performed a retrospective review of surgical pathology specimens and clinical
      data for all patients with node-positive prostate cancer diagnosed in our
      institutions between 1985 and 1994. We used adjusted actuarial survival analyses
      and univariate and multivariate analyses to evaluate the clinical significance of
      extracapsular perinodal tumor extension. Sixty patients with histologically
      confirmed prostate cancer metastatic to regional lymph nodes were reviewed. Forty
      two patients (70%) had evidence of extracapsular extension of the tumor into
      perinodal tissue. The 5-year adjusted cumulative survival rates for patients with
      extracapsular nodal extension was 54.6%, compared with 71.4% for patients with
      histologically confined nodal metastases (P < .05). Univariate and multivariate
      analyses revealed the presence of extracapsular nodal tumor extension to be an
      independent predictor of patient survival. In this study, only the histologic
      grade (Gleason score) of the primary tumor was a stronger predictive factor.
      These data suggest that histologic evidence of extracapsular tumor extension from
      lymph node metastases into perinodal tissue might be an important prognostic
      factor in patients with node-positive adenocarcinoma of the prostate. Development
      of a pathologic substage to include this feature might be warranted.

PMID- 9267824
TI  - BCL-1 (PRAD-1/cyclin D-1) overexpression distinguishes the blastoid variant of
      mantle cell lymphoma from B-lineage lymphoblastic lymphoma.
AB  - The blastoid variant of mantle cell lymphoma (MCL-BV) can occur de novo or can
      represent a morphologic transformation of MCL associated with aggressive clinical
      disease. Its cytologic appearance is very similar to that of lymphoblastic
      lymphoma (LBL) because of its characteristic nuclear features and high
      proliferative rate. To assess the usefulness of antibodies to cyclin D-1 (BCL-1/
      PRAD-1), CD99 (12E7), CD34, and TdT in distinguishing between MCL-BV and LBL in
      formalin-fixed, paraffin-embedded tissue, we studied from the Stanford data base
      10 cases originally diagnosed as B-lineage LBL, 5 MCL-BVs, 2 cases thought likely
      to represent MCL-BV, and 2 blastic lymphomas whose morphology and immunophenotype
      were indeterminate. Six (60%) of 10 LBLs stained with CD99, as opposed to none of
      7 MCL-BVs. Four (40%) of 10 LBLs reacted with CD34, as compared with none of 7
      MCL-BVs. Eight (89%) of nine LBLs were positive for TdT, but all of the four MCL
      BVs tested were negative. In contrast, the anti-cyclin D-1 antibody stained the
      nuclei of all of the MCL-BVs and none of the LBLs tested. On the basis of our
      evaluation, the probable MCL-BV cases were considered to be definite MCL-BV. Of
      the indeterminate cases, one was considered to be LBL, whereas we felt that the
      other represented MCL-BV. We conclude that staining formalin-fixed, paraffin
      embedded, high-grade lymphomas with anti-cyclin D-1 antibody is useful in
      confirming the diagnosis of MCL-BV, whereas positive reactions with CD99, CD34,
      and particularly TdT are more characteristic of LBL.

PMID- 9267825
TI  - CD23 expression in transformed small lymphocytic lymphomas/chronic lymphocytic
      leukemias and blastic transformations of mantle cell lymphoma.
AB  - The immunophenotypic marker, CD23, has been shown to be a useful marker for the
      distinction of small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL)
      from mantle cell lymphoma (MCL). The usefulness of this marker has not previously
      been analyzed in distinguishing various "large cell" transformations of SLL/CLL
      from blastic transformations of MCL (MCL-B). Thirteen cases of transformed
      SLL/CLL and six cases of MCL-B were analyzed for expression of CD23, either by
      flow cytometry of peripheral blood, bone marrow, or fresh tissue or by
      immunoperoxidase staining of paraffin-embedded archival tissue. All of the 13
      cases of transformed SLL/ CLL expressed CD23 and all of the 6 cases of MCL-B were
      negative for CD23. Therefore, CD23 is retained in transformed SLL/CLL. It is a
      useful marker in distinguishing transformed SLL/CLL from MCL-B and thus might aid
      in distinguishing those cases that present de novo without a previous diagnosis
      of SLL/CLL or MCL.

PMID- 9267826
TI  - Identification of HER-2/neu oncogene amplification by fluorescence in situ
      hybridization in stage I endometrial carcinoma.
AB  - Prognostic factors capable of detecting potential for aggressive disease in early
      stage endometrial cancer might be useful in selecting patients for early adjuvant
      therapy. Sixty-three patients with surgical Stage I endometrial carcinoma treated
      by hysterectomy with a mean follow-up of 55 months were evaluated for tumor type,
      grade, depth of myometrial invasion, presence of vascular invasion, DNA ploidy,
      and HER-2/neu overexpression by immunohistochemical techniques. These results
      were compared with HER-2/neu gene amplifications evaluated by fluorescence in
      situ hybridization (FISH) and their ability to predict disease survival. For
      FISH, sections 5 microns thick of formalin-fixed, paraffin-embedded tissues were
      processed using the Oncor Chromosome In Situ Hybridization System. Automated
      hybridization using the Ventana Gen was performed with the Oncor unique sequence
      digoxigenin-labeled HER-2/neu DNA probe. Gene copy numbers were evaluated using
      the Zeiss Axioskop50 fluorescence microscope. HER-2/neu amplification was noted
      in 24 (38%) of 63 cases. By multivariate analysis, only aneuploidy (P = .04) and
      HER-2/neu amplification by FISH (P = .04) independently correlated with survival.
      Although we saw a relationship between HER-2/neu protein expression and gene
      amplification, this trend did not achieve statistical significance. HER-2/neu
      oncogene amplification can be assessed using automated FISH on formalin-fixed,
      paraffin-embedded tissue. HER-2/ neu amplification predicts poor outcome in Stage
      I endometrial cancer. HER-2/neu amplification status has potential use in the
      identification of patients with high risk of disease recurrence who might benefit
      from intensified therapy.

PMID- 9267827
TI  - Expression of c-met proto-oncogene product (c-MET) in benign and malignant bone
      tumors.
AB  - The expression of c-met proto-oncogene product (c-MET) has been reported to be
      related to invasive growth or tumor stage in some tumors, but little is known
      concerning the significance of c-MET expression in bone tumors. With use of
      formalin-fixed, paraffin-embedded tissue specimens and polyclonal antibody for c
      MET, we studied the expression of c-MET in 122 cases of malignant bone tumors (43
      osteosarcomas, 24 chondrosarcomas, 21 malignant fibrous histiocytomas of bone, 16
      Ewing's sarcoma versus primitive neuroectodermal tumors, 18 chordomas), 65 cases
      of benign tumors and tumor-like lesions (including 8 giant cell tumors of bone, 8
      chondroblastomas, 12 enchondromas, 7 osteochondromas, 10 fibrous dysplasias), 7
      cases of articular cartilaginous tissue, and 10 cases of fetal vertebral tissue
      consisting of foci of enchondral ossification and notochordal tissue. In
      malignant tumors, c-MET expression was most frequently detected in chordoma
      (94.4%), followed by chondrosarcoma (54.2%) and osteosarcoma (23.3%). Among the
      osteosarcoma specimens, c-MET expression was frequently detected in the
      chondroblastic subtype (66.7%), but the incidence was low in the cases with other
      subtypes of osteosarcoma. We found no significant correlation between the c-MET
      expression and the histologic grade of malignancy in either osteosarcoma or
      chondrosarcoma. c-MET expression was either rarely observed or completely
      negative in malignant fibrous histiocytomas of bone (4.8%) and primitive
      neuroectodermal tumors (0%). In benign tumors and tumor-like lesions, c-MET
      expression was frequently detected in cartilaginous tumors, such as
      chondroblastoma (62.5%), enchondroma (66.7%), and osteochondroma (71.4%), but no
      expression was observed in giant cell tumors of bone or any other benign tumors
      or tumor-like lesions. In normal tissue, c-MET expression was frequently detected
      in the articular cartilage (100%) and notochord (70.0%) specimens examined. We
      conclude that c-MET expression as frequent as that observed in the notochordal
      tissue, chordomas, articular cartilage, and cartilaginous tumors is related to
      the development of both normal tissue and chondroid tumors.

PMID- 9267828
TI  - Heterogeneity of androgen receptor content in advanced prostate cancer.
AB  - The principal mode of treatment of advanced (late stage) prostate cancer is
      androgen ablation. Although the response rate to hormonal ablation is high,
      relapse ultimately leading to death occurs in the majority of patients in
      remission from outgrowth of androgen-independent tumor cells. High-grade and high
      stage cancers are more likely to progress to androgen independence. This study
      was undertaken to analyze the expression level of androgen receptor (AR) protein
      in prostatic carcinomas in relationship to grade and stage of disease. AR protein
      expression was assessed in 40 archival cases of prostate carcinoma by automated
      immunohistochemical techniques with standardized development times. Positive
      nuclei were quantitated by computer-assisted image analysis. Eighty-five percent
      of the prostatic carcinomas showed high levels of expression, defined as having
      AR present in more than 50% of the cells by light microscopy. Results of image
      analysis demonstrated that the variability of AR protein content per unit nuclear
      area increased with increasing grade (P < .03), regardless of cell size. High
      grade prostatic intraepithelial neoplasia (PIN), present in 17 (42.5%) of the 40
      cases, showed markedly reduced AR nuclear staining, compared with low-grade PIN
      or normal prostate. We show that AR content in prostate tumor cells becomes more
      variable with increasing Gleason score. In high-grade PIN, the in situ precursor
      of invasive prostate cancer, AR expression is either downregulated and/or
      restricted to the cytoplasm, but it is not heterogeneous. These data suggest that
      the heterogeneity in the expression of the receptor increases with progression of
      invasive prostate cancer and might in part account for a variable response to
      endocrine therapy.

PMID- 9267830
TI  - Re: Skoumal SM, Maygarden SJ. Malpractice in gynecologic cytology: a need for
      expert witness guidelines. Mod Pathol 1997;10:267-9.

PMID- 9267829
TI  - Pulmonary lipomatosis: a variant of placental transmogrification.
AB  - An unusual pulmonary lesion is presented. The patient is a 55-year-old white man
      with a 2-week history of pleuritic chest pain, shortness of breath, and
      bronchopneumonia. The patient had also a history of smoking and chronic cough for
      12 years. Chest radiographic studies showed a 20-cm bulla in the left upper lobe.
      A left upper lobectomy was performed obtaining an almost completely collapsed
      lobe with destruction of the normal architecture by a meshwork of yellowish
      tissue. Histologically, there were strikingly papillary structures composed
      almost exclusively of mature adipose tissue with small collections of
      inflammatory cells. Minimal emphysema in the adjacent lung parenchyma was
      observed. The case herein presented most likely represents part of the spectrum
      of placental transmogrification or placentoid bullous lesions of the lung.

PMID- 9267831
TI  - Re: Platz CE, Cohen MB, Jones MP, Olson DB, Lynch CF. Is microstaging of early
      invasive bladder cancer of the urinary bladder possible or useful? Mod Pathol
      1996;9:1035-9.

PMID- 9267833
TI  - Is psychological stress a risk factor for cerebrovascular disease?
AB  - Psychological stress has been implicated as a risk factor for a number of medical
      conditions. The association has been particularly well-studied for coronary heart
      disease. In contrast, there are only a few studies regarding the role of
      psychological stress as a risk factor for stroke. Additional research is clearly
      necessary to better delineate the degree of risk and the physiological mechanisms
      through which psychological stress may play a role in the development of
      cerebrovascular disease.

PMID- 9267832
TI  - Stroke prevention: windows of opportunity and failed expectations? A discussion
      of modifiable cardiovascular risk factors and a prevention proposal.

PMID- 9267835
TI  - Psychometric considerations when measuring cognitive decline in Alzheimer's
      disease.
AB  - Measuring cognitive decline is important for both clinical and basic research
      purposes, but to do so is a complicated methodologic and statistical exercise.
      Some promising predictive measures have been identified, such as baseline
      severity of disease, early language deterioration, other early behavioral
      disturbance and extrapyramidal signs. Nevertheless, investigations of
      demographic, cognitive and biologic variables have not consistently identified
      factors affecting differences in the course or rate of decline. Moreover,
      contradictory results using similar measures are common. Such contradictory
      results may be attributed, in part, to differences among samples, cognitive tests
      selected, research design, and methods of statistical analysis. Large samples of
      patients with dementia examined repeatedly for long time periods are needed.
      However, tests developed for initial screening, diagnosing and categorizing
      Alzheimer's disease are not necessarily the most appropriate for longitudinal
      studies of disease course. New instruments with a broader range of item
      difficulty, and less susceptibility to floor and ceiling effects must be
      developed. Also, standardized ways of defining cognitive decline are needed which
      are more sophisticated than simple change scores. Standardization will improve
      the ability to compare investigations and perhaps reconcile apparent differences
      in results.

PMID- 9267834
TI  - Secular trends in stroke mortality in African Americans: the role of
      urbanization, diabetes and obesity.
AB  - The decline in stroke mortality rates in African Americans has slowed to that
      seen in the 1960s; rates remain higher than in European Americans. Rates are
      higher in the southeastern US and in nonmetropolitan areas. Adverse trends and
      patterns in diabetes, obesity, and heart disease prevalence are possible
      explanations. Unless new, effective prevention programs are introduced in African
      American communities, stroke mortality rates will decline slowly if at all. The
      best chance to increase the rate of decline in stroke mortality rates in African
      Americans may be to redouble efforts to achieve the goals for the year 2000.
      Community and patient education on improving diet, increasing exercise, further
      improving detection and control of hypertension, using aspirin in stroke
      prevention and active control of stroke risk factors in diabetics must be
      stressed.

PMID- 9267837
TI  - Epidemiology of myasthenia gravis in northwestern Sardinia.
AB  - A previous epidemiological study on myasthenia gravis (MG) in Sardinia indicated
      a prevalence rate of 4.5 per 100,000 population and an incidence of 0.25 per
      100,000 population in the period 1958-1986. This study, however, investigated the
      entire Sardinian population (about 1,500,000) and the reported rates are likely
      to be underestimated. Because the use of a very large population has been found
      to cause major bias in case finding, the present study was designed to overcome
      this bias by determining the prevalence and incidence of MG in a well-defined
      area of Northwestern Sardinia, with a population of about 270,000 (1991 census).
      Potential MG cases were ascertained using all possible medical sources. The
      diagnosis of MG was based on the clinical, neurophysiological and conventional
      pharmacological findings (Tensilon test, response to anticholinesterases). On
      prevalence day (December 31, 1994) 29 MG patients were living in the study area
      (17 women and 12 men). Since the total population on prevalence day was 268,926
      (137,284 women and 131,642 men), the calculated prevalence was 11.1 per 100,000
      population (12.4 women and 9.9 men). The present study shows that the risk of MG
      in Sardinia is higher than previously suggested. The risk, however, is not
      significantly different from that found in other comparable Italian and European
      areas. It contrasts with what has been found for other autoimmune diseases such
      as multiple sclerosis and insulin-dependent diabetes mellitus in Sardinians, both
      showing frequencies up to 3-5 times higher than in the rest of Italy.

PMID- 9267836
TI  - The effect on risk estimates of excluding cases from a case-control study of
      ischemic stroke.
AB  - There is limited information about the effect on stroke risk estimates of
      excluding cases who are unable to respond to interviews. A case-control study of
      ischemic stroke between 1988 and 1990 in Shreveport, La., USA, provided a basis
      for studying this question. Of 197 consecutively admitted cases of ischemic
      stroke, 77 were excluded due to dementia, aphasia or impaired consciousness.
      Information about risk factors and stroke characteristics was obtained from
      hospital records. Excluded cases had more left hemispheric (52 versus 19%) and
      fewer vertebrobasilar (12 versus 29%) and lacunar (5 versus 13%) infarcts than
      included cases. Excluded cases were also older (p < 0.01), and they had larger
      infarcts (p < 0.01), multiple strokes (p < 0.01) and congestive heart failure (p
      < 0.01) more often than included cases. Cases were matched to hospital controls
      by age, sex, race, and date of admission. Odds ratios (ORs) were higher for
      excluded cases for 5 of 6 exposures with a significantly higher OR for congestive
      heart failure (p < 0.01). The ORs changed by as much as 63% when excluded cases
      were added. These results emphasize the importance of acquiring information about
      excluded cases and considering selection bias when interpreting stroke studies
      that exclude cases who are unable to respond to interviews.

PMID- 9267838
TI  - Epilepsy and everyday life risks. A case-referent study: rationale, study design,
      and preliminary results. Risk in Epilepsy Study Group.
AB  - Despite its favorable outcome in up to 90% of patients, epilepsy is still
      considered to carry a higher than normal risk of morbidity and accidents.
      Knowledge of the everyday life risks (illnesses, accidents) in patients with
      epilepsy is mostly anecdotal. For these reasons, a multinational cohort study has
      been started in 9 European countries to investigate the incidence and number of
      medical events and accidents in children and adults with unprovoked epilepsy
      (diagnosed in the recruiting centers in the previous 10 years) and in age- and
      sex-matched controls (relatives or friends). The 2 groups are being followed for
      at least 12 months. Using patients' diaries, data are being collected regarding
      the number and type of illnesses and accidents, the number of medical contacts
      and the actions taken, the number of hospital admissions, and the total number of
      days off work/school. In a preliminary report on 833 patients and 833 controls,
      the cases reported slightly less illnesses, medical contacts, and actions taken
      by doctors. Accidents and related events occurred in similar proportions in the 2
      groups. Based on the results of the pilot study, idiopathic, cryptogenic and
      remote symptomatic epilepsy may be compatible with an at least fairly normal
      social life.

PMID- 9267840
TI  - The scope of gene therapy in humans: scientific, safety and ethical
      considerations.
AB  - Gene therapy entails the introduction of specific, functional genes into cells
      for therapeutic or preventive purposes. Therapeutic genes may be introduced into
      cells in vitro (and the treated cells then introduced into the patient) or
      directly in vivo. Gene therapy may be used for several purposes including: (a)
      Gene replacement in genetic diseases; (b) Destroying malignant cells in
      neoplastic diseases; (c) Modifying immune responses; (d) Providing trophic
      molecules; (e) Immunisation against infectious diseases. In designing gene
      therapy strategies the following major items need to be investigated and
      optimised: (1) Relevant biological characteristics of the treatable cells and
      tissues; (2) Gene vectors (viral or non-viral); (3) The gene expression cassette
      (promoter+cDNA+poly A signal); (4) The safest and most effective route of
      administration; (5) Longevity of the transgene expression. Before human trials
      for gene therapy can commence for a given disease, extensive preclinical studies
      are to be carried out in an appropriate experimental models to assure the
      feasibility, safety and efficiency of the enterprise. For each disease or
      application, the risk/benefit ratio must be determined. Permission by regulatory
      agencies, institutional review boards (IRB) and thorough informed consent are
      essential. Although gene therapy holds great promise for many human diseases, it
      is still too early to predict the extent and timetable of its successful
      implementation in individual diseases.

PMID- 9267841
TI  - Improved adenoviral vectors for gene therapy of Duchenne muscular dystrophy.
AB  - We have been exploring the feasibility of gene therapy for Duchenne muscular
      dystrophy by characterizing parameters important for the design of therapeutic
      protocols. These studies have used transgenic mice to analyze expression patterns
      of multiple dystrophin vectors, and have been accompanied by the development of
      viral vectors for gene transfer to dystrophic mdx mouse muscle. Analysis of
      transgenic mdx mice indicates that greater than 50% of the fibers in a muscle
      group must express dystrophin to prevent development of a significant dystrophy,
      and that low-level expression of truncated dystrophins can function very well.
      These results suggest that gene therapy of DMD will require methods to transduce
      the majority of fibers in critical muscle groups with vectors that express
      moderate levels of dystrophin proteins. Strategies for the development of viral
      vectors able to deliver dystrophin genes to muscle include the use of muscle
      specific regulatory sequences coupled with deletion of viral gene sequences to
      limit virus-induced immune rejection of transduced tissues. These strategies
      should enable production of adenoviral vectors expressing full-length dystrophin
      proteins in muscle.

PMID- 9267842
TI  - Strategies to accomplish targeted gene delivery to muscle cells employing tropism
      modified adenoviral vectors.
AB  - We are developing strategies to modify the tropism of adenoviral vectors to
      accomplish targeted transduction of muscle cells for DMD gene therapy. In one
      approach, we have introduced targeting ligands into the adenovirus fibre, which
      mediates the binding of the virus Ad5 to the primary cellular receptor. In order
      to incorporate these fibre-ligand fusions into recombinant adenoviral vectors, we
      have employed a method based upon homologous DNA recombination between a fibre
      deleted, propagation-defective rescue plasmid and a shuttle plasmid encoding a
      variant fibre. To date, we have generated an adenoviral vector containing
      chimeric fibres composed of the tail and shaft domains of adenovirus serotype 5
      and the knob domain of serotype 3. This modification altered the receptor
      recognition profile of the virus containing the fibre chimera. In an alternative
      approach to the generation of a targeted adenoviral vector, we conjugated folate
      to the neutralising Fab fragment of an anti-fibre monoclonal antibody. This Fab
      folate conjugate was shown to redirect adenoviral infection of target cells via
      the folate receptor at a high efficiency. These studies suggest that it will be
      possible to achieve our goal of deriving targeted adenoviral vectors for muscle
      cell-specific gene delivery in vivo.

PMID- 9267843
TI  - Gene transfer to muscle using herpes simplex virus-based vectors.
AB  - The main goal of gene therapy for Duchenne muscular dystrophy (DMD) is to restore
      dystrophin into as many muscle cells as necessary to be therapeutic. Herpes
      simplex virus type 1 (HSV-1) represents a promising new viral vector capable of
      efficient transduction of myofibers in vivo. The viral genome is large and can
      accommodate multiple or large non-viral genes including the full-length
      dystrophin. Here we report on the use of a replication defective HSV-1 mutant
      vector (DZ) deleted for the essential immediate early (IE) gene ICP4 for studies
      of reporter gene transfer and expression following direct inoculation of mouse
      skeletal muscle. Our initial experiments showed that HSV-1 can efficiently infect
      and express a foreign reporter gene in myoblasts and myotubes in vitro.
      Furthermore, the intramuscular inoculation of HSV-1 resulted in transduction of a
      significant number of muscle fibers in newborn mice and some muscle fibers in
      adult animals. We have attempted to exploit these features to develop new HSV
      mutant vectors for dystrophin gene delivery to DMD muscle, however two
      impediments to using this virus for muscle gene delivery have to be overcome:
      namely viral cytotoxicity and the differential transducibility with HSV-1
      throughout the development of muscle fibers. To solve the first problem, virus
      mutants deleted for the immediate early (IE) genes (ICP4, ICP22, ICP27 and UL41)
      were constructed and the multiple deleted virus was greatly reduced in
      cytotoxicity relative to our first generation HSV vector strains. Current work is
      aimed at incorporating full-length dystrophin under muscle specific promoter
      (muscle creatine kinase MCK) into these new viral vectors. To address the second
      problem we have analysed by immunohistochemistry the spreading of the HSV-1 in
      newborn versus adult muscles to determine whether mature basal lamina which
      surrounds the adult muscle fibers blocks the HSV-1 entry into the mature muscle
      fibers.

PMID- 9267844
TI  - Naked DNA transport and expression in mammalian cells.
AB  - The tremendous promise of gene therapy is stymied by inefficient gene transfer.
      Non-viral methods of transferring genes directly into tissues in situ have great
      potential for solving this problem. One attractive approach for non-viral direct
      gene transfer is the use of naked DNA. Previously, it was thought that naked DNA
      was able to express in only muscle and at low efficiency. We have recently found
      that naked DNA delivered intraportally can express at high levels in hepatocytes.
      Other non-viral methods of gene transfer are under development and these include
      ternary complexes of histone protein and liposomes. Besides trial-and-error
      approaches, the mechanism of the nuclear entry of plasmid DNA, a critical step,
      has been under intense study. It is anticipated that further advances in the
      efficiency of direct, non-viral gene transfer will enable its use in clinical
      settings in the near future.

PMID- 9267845
TI  - Problems and potential for gene therapy in Duchenne muscular dystrophy.
AB  - Hopes ran high that a cure for Duchenne muscular dystrophy (DMD) would quickly
      follow the discovery of dystrophin by Lou Kunkel and his group in the 1980's.
      Myoblast transplantation, the favoured method of gene 'complementation',
      unfortunately did not progress beyond the experimental stage. A more sober
      approach to gene therapy followed using a variety of transfection or direct
      methods to introduce the normal gene. In view of these advances it is timely for
      the potential of gene therapy for DMD to be considered in the light of the
      disease process. It may be assumed that if dystrophin is replaced muscle fibre
      necrosis will cease. For this purpose expression of the gene should be continuous
      and expressed throughout the body well before there are irreversible changes. It
      would seem that gene therapy would not be particularly helpful if this occurs
      when the muscle lesions are near the end stage. If our objective is to retain
      ambulation dystrophin must be replaced well before the end stage. It should be
      kept in mind that even when the disorder first becomes clinically apparent at the
      age of about 5 years, muscle lesions are very advanced in the limb girdle groups.
      Therefore, the best that may be hoped to achieve by gene therapy at the age of 5
      years would be to arrest the process at that stage of involvement with the
      patient having permanent but static weakness. Cardiac lesions are probably
      minimal at this time. To improve life expectancy, the respiratory muscles would
      need to be preserved. The enormous size of the gene is another difficulty so that
      some thought has been given to the introduction of a 'minigene' converting the
      clinical phenotype from DMD to the more benign Becker phenotype with improved
      life expectancy.

PMID- 9267846
TI  - Use of the dog model for Duchenne muscular dystrophy in gene therapy trials.
AB  - Golden retriever muscular dystrophy (GRMD) is an excellent model for the study of
      the efficacy of gene therapy in dystrophin deficient myopathies for there are
      many similarities between affected dogs and Duchenne muscular dystrophy (DMD) in
      boys. GRMD is not caused by deletion mutation but results from a point mutation
      in the consensus splice acceptor in intron 6 of the canine dystrophin gene. As a
      result exon 7 is skipped during processing of the GRMD dystrophin messenger RNA.
      We have developed a rapid test which makes direct use of exon 7 specific genomic
      PCR products. We have undertaken preliminary experiments on gene therapy using
      the mini-gene and the full length gene alone and in combination with lipofectin
      and/or the bacterial beta-galactosidase reporter gene Lac Z. Following direct
      injection of the Lac Z plasmid, either alone or with lipofectin, about 50% of the
      sites showed expression when biopsied some 14 days later. The beta-galactosidase
      activity was present in muscle and granulation tissue but was never abundant.
      Pups injected intraperitoneally with Lac Z were found to have positive material
      in their mesenteric lymph nodes, liver and spleen. Those injected with Lac Z and
      lipofectin also had positive material in the diaphragm, intercostal muscles and
      abdominal muscles, but again only a small amount of positive material was present
      at any of the sites. In animals directly injected into the muscle with the
      dystrophin mini-gene, half had positive staining for dystrophin in biopsies taken
      14 days later. Of the 6 sites in the muscles of animals given the mini-gene and
      lipofectin only one had fibres positive for dystrophin when examined 14 days
      later. Six pups were injected directly with full-length gene construct and when
      biopsies were taken 10 days later two of the animals had strongly stained
      peripheries to a small number of fibres.

PMID- 9267847
TI  - Revertant fibres: a possible genetic therapy for Duchenne muscular dystrophy?
AB  - The mdx mouse, an animal model used to study Duchenne muscular dystrophy (DMD),
      has a nonsense mutation in exon 23 of the dystrophin gene which should result in
      a truncated protein that cannot be correctly localized at the sarcolemma of the
      muscle fibres. Immunohistochemical staining with anti-dystrophin antibodies had
      shown that while most of the muscle tissue was dystrophin-negative, a small
      percentage of muscle fibres were clearly dystrophin-positive and had somehow by
      passed the primary nonsense mutation. A nested PCR-based examination of
      dystrophin gene transcripts around the mdx mutation revealed several
      alternatively processed transcripts, of which four mRNA species skipped the
      mutation in exon 23, were in-frame and could be translated into a shorter, but
      still functional dystrophin protein. Specific tests for these transcripts
      demonstrated these were also present in normal adult and embryonic mouse muscle
      tissue.

PMID- 9267848
TI  - A splice-site mutation causing ovine McArdle's disease.
AB  - McArdle's disease is an autosomal recessive myopathy with symptoms of exercise
      intolerance caused by deficiency of the enzyme muscle glycogen phosphorylase
      which releases glucose for contraction during exercise. The human cDNA has been
      sequenced and disease-causing mutations identified. An ovine equivalent of
      McArdle's disease has been diagnosed and the mutation responsible identified by
      PCR-amplification of the ovine glycogen myophosphorylase cDNA in six overlapping
      fragments followed by single strand conformation polymorphism (SSCP) analysis.
      Two fragments showed SSCPs in the glycogen myophosphorylase cDNA from affected
      sheep. The SSCP in fragment one was a silent polymorphism, while that in fragment
      six, was an eight base deletion at the 5' end of exon 20. This deletion will
      cause a frame-shift, a premature stop codon and remove the last 31 amino-acid
      residues from the protein. The cDNA deletion suggested that the genomic mutation
      most likely involved a splice-site. Sequencing intron 19 identified the mutation
      as an adenine for guanine substitution at the intron 19 3' splice-site. This
      eliminated an XbaI site present in normal sheep allowing diagnosis of normal,
      affected and carrier sheep. This ovine model of McArdle's disease is now
      available for therapeutic trials.

PMID- 9267849
TI  - Cell vehicles for gene transfer to the brain.
AB  - Gene products of therapeutic value have been delivered directly to the brain by
      viral and physical transfer methods and indirectly using cell delivery vehicles.
      Neural precursor cells, produced by immortalization or expansion with growth
      factors (e.g. fibroblast growth factor (FGF2)), offer promise both as vehicles
      for gene delivery to the brain and for their inherent ability to differentiate
      into neurons and glia in vivo. Their ability to migrate widely throughout the
      brain after injection, and to integrate in a functional and non-disruptive manner
      are key advantages over non-neural cells. In mouse models of neurodegenerative
      disease, transplanted neural precursor cells performed dual functions; they acted
      as a gene delivery vehicle, supplying a deficient enzyme, and provided some
      neuroglial cell functions which had been lost. Genetically modified neural
      precursor transplants influenced the development of inherited neurological
      disease, establishing the feasibility of this novel approach as a treatment for
      neurodegenerative disorders.

PMID- 9267850
TI  - Gene therapy for murine mucopolysaccharidosis type VII.
AB  - Mucopolysaccharidosis type VII (MPS VII) is caused by a deficiency in the
      lysosomal enzyme beta-glucuronidase resulting in the accumulation of undegraded
      glycosaminoglycans in many tissues. A murine model of MPS VII shares many of the
      clinical, biochemical and histopathological features of human MPS VII and has
      provided an opportunity to study novel therapeutic approaches in a system with a
      uniform genetic background. Retroviral mediated gene therapy directed to the
      hematopoietic system or to artificial neo-organs resulted in low levels of enzyme
      in several tissues and reduced lysosomal storage in the liver and spleen. Partial
      correction of the disease in the eye was observed following an intravitreal
      injection of recombinant adenovirus. Neither retroviral nor adenoviral mediated
      gene transfer techniques resulted in a systemic reduction of lysosomal storage.
      Here we discuss several novel gene transfer approaches designed to increase the
      systemic levels of beta-glucuronidase in the MPS VII mouse.

PMID- 9267851
TI  - Canine fucosidosis: a model for retroviral gene transfer into haematopoietic stem
      cells.
AB  - Severe progressive fatal neurological degeneration occurs in fucosidosis, a
      storage disease. Bone marrow transplantation into affected dogs has shown that
      haematopoietic stem cells can provide enzyme producing daughter cells to the
      central nervous system, altering disease course. This makes canine fucosidosis an
      ideal large animal model for gene therapy. Fucosidosis affected allogeneic or
      autologous canine marrow was transduced ex vivo by cocultivation, then
      transplanted into fucosidosis affected dogs conditioned with total lymphoid
      irradiation. The vectors were Moloney murine leukaemia virus based. Transduction
      efficiency was increased with multiple cytokines in short term marrow culture.
      Despite high levels of transduction, proviral sequence was detected 2 months post
      transplant in only one dog. Early or total graft failure occurred in all
      transplants. We believe lack of engraftment could be caused by differentiation or
      change of repopulating ability of marrow cells occurring with multiple cytokine
      mixes in culture media.

PMID- 9267852
TI  - Motor activity and daily variation of symptom intensity in depressed patients.
AB  - Spontaneous motor activity measured by actigraphy and subjectively experienced
      intensity of symptoms were investigated in 16 unipolar depressed inpatients with
      melancholic features. Patients felt significantly less active, awake, and more
      depressed in the morning compared to the evening. However, morning activity
      levels appeared significantly higher compared to evening levels. Diurnal
      variations of symptoms were reflected by actigraphically measured motor activity,
      which was negatively correlated with subjectively experienced symptom intensity.
      Increased motor activity may represent an observable, psychobiological,
      behavioral equivalent of self-experienced depressive symptoms in major depression
      with melancholic features.

PMID- 9267853
TI  - Positive association between the GABRA5 gene and unipolar recurrent major
      depression.
AB  - The gamma-aminobutyric acid (GABA) neurotransmitter system has been implicated in
      the pathogenesis of mood disorders. To test this hypothesis we carried out an
      association study between a dinucleotide repeat polymorphism in the GABAA
      receptor alpha 5 subunit gene and bipolar and unipolar mood disorders. Our
      results suggest a possible involvement of this gene in unipolar but not in
      bipolar disorder.

PMID- 9267854
TI  - Haloperidol administration in humans lowers plasma nerve growth factor level:
      evidence that sedation induces opposite effects to arousal.
AB  - Studies reported in recent years have indicated that the level of nerve growth
      factor (NGF), in both the brain and in the bloodstream, increases following
      stressful events and anxiety-associated behaviour. These observations prompted us
      to investigate whether an anti-arousal drug would induce an opposite effect. We
      have reported that the administration of haloperidol (HA), a neuroleptic drug
      clinically used for psychiatric disorders, decreases NGF levels in the
      hypothalamus of adult male mice. In the present study, we showed that HA reduced
      the basal NGF plasma levels in 8 neuroleptic-free schizophrenic patients. These
      observations strengthen the hypothesis that NGF may play a functional role in
      stress-coping responses.

PMID- 9267855
TI  - Biperiden and haloperidol plasma levels and extrapyramidal side effects in
      schizophrenic patients.
AB  - Anticholinergic drugs such as biperiden are used for the treatment of
      extrapyramidal side effects (EPS) induced by neuroleptics such as haloperidol.
      The effects of biperiden and haloperidol plasma levels on EPS were studied in 29
      chronically ill schizophrenics. The results show relationships between biperiden
      dose and biperiden plasma levels (BPL), and between BPL and haloperidol plasma
      levels (HPL). Neither BPL nor HPL seem to influence EPS.

PMID- 9267856
TI  - A controlled study of 2 doses of idebenone in the treatment of Alzheimer's
      disease.
AB  - Two doses of idebenone were studied in a prospective, randomized, double-blind,
      placebo-controlled multicentre study in patients suffering from dementia of the
      Alzheimer type (DAT) of mild to moderate degree. Diagnosis was based on DSM-III-R
      (primary degenerative dementia) and NINCDS-ADRDA criteria (probable Alzheimer's
      disease). A total of 300 patients were randomized to either placebo, idebenone 30
      mg t.i.d. or 90 mg t.i.d. (n = 100, each) and treated for 6 months. The primary
      outcome measure was the total score of the Alzheimer's Disease Assessment Scale
      (ADAS-Total) at month 6. Secondary outcome measures were the ADAS cognitive (ADAS
      Cog) and noncognitive scores (ADAS-Noncog), the clinical global response (CGI
      Improvement), the MMSE, the Digit Symbol Substitution test (DSS) and several
      scales for the assessment of daily activities (the self- and observer-rating
      scales NAA and NAB of the Nuremberg Age Inventory NAI and Greene's Assessment).
      Safety parameters were adverse events, vital signs, ECG and clinical laboratory
      parameters. Clinical and psychometric evaluations were performed at baseline, and
      after 1, 3 and 6 months of treatment. After month 6 idebenone 90 mg t.i.d. showed
      statistically significant improvement in the primary efficacy variable ADAS-Total
      and in ADAS-Cog. An analysis of therapy responders performed for 3 outcome
      measures (CGI-global improvement, ADAS-Cog, ADAS-Noncog), selected to represent
      different domains of assessment, revealed significant superiority of idebenone 90
      mg t.i.d. with respect to placebo in each of the 3 variables and in the
      concordance of responses across the 3 measures. Exploratory results for a
      subgroup of patients (ADAS-Total > or = 20) showed dose-related superiority of
      idebenone additionally on ADAS-Noncog and the CGI-Improvement scale. Safety
      results were inconspicuous for all assessments. The study results demonstrate the
      efficacy and safety of idebenone in the treatment of DAT patients.

PMID- 9267857
TI  - Sensory gating deficit following cocaine exposure in the rat.
AB  - The purpose of this research was to examine changes in the ratio and amplitude of
      the N40 component of the auditory event-related potential (ERP) in the paired
      conditioning (C) test (T) stimulation paradigm following subchronic
      cocaine/vehicle administration. Free moving rats received cocaine (47.5 mg/kg) or
      saline for 7 consecutive days in a longitudinal crossover design. ERPs were
      recorded 4 and 7 days after each treatment and again 4 and 7 days following
      withdrawal of the drug/vehicle. Cocaine led to a progressive increase in the T/C
      ratio indicating impaired inhibition of the test response. This trend continued
      throughout the 7-day drug regimen. Following withdrawal of the drug the T/C ratio
      gradually normalized over the next 7 days but remained elevated at 4 days
      postdrug. A significant increase in the test response accompanied by a less
      pronounced decrease in the conditioning response accounted for the observed
      results. Behavioral state as measured on a rating scale during ERP sampling did
      not differ across experimental conditions.

PMID- 9267858
TI  - Cholecystokinin-induced effects on selective attention depend on level of
      activation.
AB  - Cholecystokinin (CCK)-like peptides, such as ceruletide, have been found to
      improve selective attention as indicated by the processing negativity (PN) of the
      event-related brain potential. The present study compared effects of ceruletide
      and placebo after intravenous administration of ceruletide on the PN in healthy
      subjects classified into two groups scoring high versus low on self-reported
      activation. Following placebo, PN (at Fz) was somewhat larger in subjects with
      low than high activation (p < 0.1). Administration of the CCK analog decreased PN
      in low-activation subjects but increased PN in the highly activated group (p <
      0.01). Results suggest that the effects of CCK on selective attention depend on a
      modulation of central nervous mechanisms underlying activation.

PMID- 9267859
TI  - The effect of intravenous administration of delta-9-tetrahydrocannabinol on the
      activity of A10 dopamine neurons recorded in vivo in anesthetized rats.
AB  - In this pilot study, we examined the effect of the intravenous administration of
      delta-9-tetrahydrocannabinol (THC) on the activity of spontaneously active A10
      dopamine (DA) neurons of anesthetized, male albino rats. This was accomplished
      using the technique of in vivo extracellular single-unit recording. The
      administration of THC (0.05-1.6 mg/kg i.v.) did not significantly alter either
      the basal firing rate or the firing pattern of spontaneously active A10 DA
      neurons compared to vehicle controls. Our findings suggest that, unlike a number
      of drugs of abuse, THC does not alter the activity of A10 DA neurons and that the
      previously reported THC-induced increase in brain DA levels is not due to its
      action on firing rate or pattern in A10 DA neurons.

PMID- 9267861
TI  - Determination of de novo synthesized amino acids in cellular proteins revisited
      by 13C NMR spectroscopy.
AB  - 13C nuclear magnetic resonance spectroscopy was used to determine the absolute
      amounts to de novo synthesized amino acids in both the perchloric acid extracts
      and the hydrolyzed protein fractions of F98 glioma cells incubated for 2 h with 5
      mmol/l [U-13C]glucose. 13C NMR spectra of the hydrolyzed protein fraction
      revealed a marked incorporation of 13C-labelled alanine, aspartate and glutamate
      into the proteins of F98 cells within the incubation period. Additionally, small
      amounts of 13C-labelled glycine, proline and serine could unambiguously be
      identified in the protein fraction. Astonishingly, approximately equal amounts of
      13C-labelled glutamate and aspartate were incorporated into the cellular
      proteins, although the cytosolic steady-state concentration of aspartate was
      below 13C NMR detectability. Hypertonic stress decreased the incorporation of 13C
      labelled amino acids into the total protein, albeit their cytosolic
      concentrations were increased, which reflects an inhibition of protein synthesis
      under these conditions. On the other hand, hypotonic stress increased the amount
      of 13C-labelled proline incorporated into the cellular proteins even though the
      cytosolic concentration of 13C-labelled proline was largely decreased.
      Apparently, hypoosmotic conditions stimulate the synthesis of proteins or
      peptides with a high proline content. The results show that already after 2 h of
      incubation with [U-13C]glucose there is a pronounced flux of 13C label into the
      cellular proteins, which is usually disregarded if cytosolic fluids are examined
      only. This means that calculations of metabolic fluxes based on 13C NMR
      spectroscopic data obtained from perchloric acid extracts of cells or tissues and
      also from in vivo measurements consider only the labelled 'NMR visible' cytosolic
      metabolites, which may have to be corrected for fast label flowing off into other
      compartments.

PMID- 9267860
TI  - The AMDP modules I-IV: recommendations for a standardized acquisition of EEG data
      in psychiatry. Association for Methodology and Documentation in Psychiatry.
AB  - During the last few years, the working group 'Psychophysiology' of the
      Association for Methodology and Documentation in Psychiatry (AMDP) discussed the
      possibility of the establishment of defined EEG modules in psychiatry. It was the
      aim to create a common data pool in order to be able to have access to larger
      data sets. The installation of such a common data pool was regarded as an
      important prerequisite for a future diagnostic application of EEG and EP data in
      clinical practice. The most relevant arguments are: From a statistical point of
      view, multivariate investigations can be improved when relatively large data sets
      are available. Subgrouping of patients is facilitated. Different centers have
      access to different populations of patients. Furthermore, compliance with the
      recommendations contributes to a reduction in misunderstanding and false
      interpretation of other investigators' results. The working group
      'Psychophysiology' of the AMDP now recommends EEG modules to be registered in
      psychiatry. The recommendations are based on investigations using these modules
      in clinical research and practice as well as several years of discussion within
      the working group. Four AMDP modules (I-IV) are presented: MI: resting EEG
      (closed eyes), MII: resting EEG (eyes open), MIII: EEG during videotracking, and
      MIV: EEG during choice reaction time. Recommendations for additional modules are
      planned in the near future: MV: EEG during geometry test, MVI: EEG during
      labyrinth test, and MVII: amplitude stimulus intensity function. MIII-MVI is
      paralleled by an EEG recording so that psychomotor performance can be measured
      and EEG data under different activation conditions are available. Compliance with
      the recommendations guarantees the possibility of access to the common data pool.
      Computer software is available in Berlin.

PMID- 9267862
TI  - A study of the contribution of changes in the cerebral blood volume to the
      haemodynamic response to anoxia in rat brain.
AB  - A susceptibility contrast agent which does not pass into the extra-cellular space
      was used to study the effect of changes in the relative cerebral blood volume
      (CBV) on the haemodynamic response to anoxia, for both normal and ischaemic brain
      tissue, in a rat model of acute focal ischaemia. In non-ischaemic tissue a strong
      CBV component was observed in the haemodynamic response, both during and after
      anoxia. During anoxia the change in the CBV of the non-ischaemic tissue was
      estimated to be 40% in the caudate putamen and 70% in the frontal-parietal
      cortex. For severely ischaemic tissue (ischaemic caudate putamen) there was no
      change in the CBV during anoxia while in areas of moderate ischaemia (ischaemic
      frontal parietal cortex) a change of 20% was observed. The effect of the contrast
      agent on spin-echo images was consistent with a small reduction in the
      microvascular blood volume of the ischaemic tissue.

PMID- 9267863
TI  - Kinetics of ATP to ADP beta-phosphoryl conversion in contracting skeletal muscle
      by in vivo 31P NMR magnetization transfer.
AB  - The rate constant of the beta-adenosine triphosphate to beta-adenosine
      diphosphate conversion was measured using 31P nuclear magnetic resonance
      magnetization transfer in resting and contracting in vivo rat skeletal muscle.
      Theoretically, the rate constant should be the sum of the rate constants of the
      reactions catalyzing ATP-ADP exchange. In resting muscle, the conversion rate
      constant was 0.4 s-1 and beta-ATP intrinsic T1 was 1.7 s. The velocity of
      conversion was 3.8 mM s-1. During stimulation, phosphocreatine fell to 36% and
      ATP to 82% of initial values. The rate constant and velocity of beta-phosphoryl
      conversion increased to 0.8 s-1 and 6.3 mM s-1, respectively, but did not reach
      expected levels, i.e. the product of the ATP concentration with the sum of pseudo
      first-rate constants of the individual reactions. These conversion velocities
      should be higher than reverse creatine kinase velocities, previously measured to
      be 10 mM s-1 in resting muscle and 7.5 mM s-1 in contacting muscle and confirmed
      in this work. The discrepancy between expected and observed data could be due
      either to compartmentation of part of the beta-ATP in pools exchanging slowly
      with the bulk of cellular ATP, or to ADP binding to macromolecules thus
      preventing full ADP saturation during magnetization transfer.

PMID- 9267864
TI  - Differential distribution of NAA and NAAG in human brain as determined by
      quantitative localized proton MRS.
AB  - Quantitative proton magnetic resonance spectroscopy was performed in frontal,
      parietal and occipital white and gray matter of young adults with use of a fully
      relaxed, short-echo time stimulated echo acquisition mode localization sequence
      at 2.0 T. Separate concentrations of the neuronal compounds N-acetylaspartate
      (NAA) and N-acetylaspartylglutamate (NAAG) were obtained by user-independent
      spectral analysis (LCModel). Except for occipital gray matter in which an NAA
      concentration of 10.1 +/- 1.0 mM correlated with enhanced neuronal density in
      visual cortex, NAA was found to be homogeneously distributed throughout cortical
      white and gray matter at a concentration of 8.0-8.9 mM. NAAG concentrations of
      1.5-2.7 mM were higher in white matter than levels of 0.6-1.5 mM found in gray
      matter, contributing up to 25% of total N-acetyl-containing compounds. The
      frontal to parieto-occipital increase of both gray and white matter NAAG levels
      is also reflected in the distribution of total NAA.

PMID- 9267865
TI  - The application of diffusion-weighted line-scanning for the rapid assessment of
      water ADC changes in stroke at high magnetic fields.
AB  - Rapid changes in the apparent diffusion coefficient of water following brain
      ischemia have been extensively studied using echo planar diffusion imaging at low
      fields (2.0 T). There is a desire to perform these studies at higher fields (>
      3.0 T) where the benefits of improved signal-to-noise can be exploited.
      Unfortunately, EPI diffusion is technically difficult to implement at high fields
      because of large magnetic susceptibility effects. This article demonstrates the
      feasibility of employing a line-scan diffusion protocol for ADCw measurements in
      stroke. The technique was applied on a 4.0 T system to monitor the decline in
      ADCw following the induction of focal cerebral ischemia in rat. ADCw data were
      acquired every 15 s with 10 b-values or every 22.5 s with 15 b-values, with a
      cubic spatial resolution of 1.5 mm. The results demonstrate that estimates of
      ADCw can be acquired with coefficients of variation under 3.0%, and with a
      combination of spatial and temporal resolution comparable to that previously
      reported for EPI.

PMID- 9267866
TI  - In vivo characterization of Gd(BME-DTTA), a myocardial MRI contrast agent: tissue
      distribution of its MRI intensity enhancement, and its effect on heart function.
AB  - We have determined an LD50 of 0.56 +/- 0.05 mmol/kg for liposomal Gd(BME-DTTA) in
      mice and also shown that liposomal Gd(BME-DTTA) has no deleterious effects on
      heart rate, blood pressure, left ventricular force and AV conductance in ferret
      hearts in vivo at the magnetic resonance imaging (MRI)-effective dose of 0.05
      mmol/kg body weight. In MRI images, a 1H signal intensity enhancement is observed
      in the following organs in decreasing order of the effect: heart approximately
      spleen > kidney > liver. This enhancement is stable for over 3 h in all organs.
      The results of 1H MRI and electron micrographs indicate that the lipophilic fatty
      acyl groups in the ligand BME structure and the particle sizes of liposomal
      Gd(BME-DTTA) are two important factors for tissue specificity of liposomal Gd(BME
      DTTA) in the intensity enhancement. In vitro relaxivity of a liposomal Gd(BME
      DTTA) sample, stored at 4 degrees C, remained stable for over 4 months of
      observation, but a significant decrease in relaxivity was observed in a sample
      stored at room temperature, most likely reflecting some deterioration in liposome
      chemistry.

PMID- 9267867
TI  - Active management of labor: a meta-analysis of cesarean delivery rates for
      dystocia in nulliparas.
AB  - The objective of this article is to determine through meta-analysis of published
      literature whether active management of labor lowers the cesarean delivery rate
      for dystocia in nulliparas. Using MEDLINE and reference citations to 1966, 18
      published reports in English on active management of labor were identified.
      Selection criteria for five selected studies included: tenets of active
      management followed, detailed description of patient selection and analysis,
      numerical data on cesarean deliveries for dystocia in nulliparas, and use of a
      control group. Data on cesarean deliveries performed on nulliparas for dystocia
      were abstracted onto 2 x 2 tables by both authors independently (one blinded to
      study authors, journal, institution, and conclusions), and quality ratings
      independently assessed. Differences were resolved by consensus. Individual odds
      ratios were calculated, with summary odds ratios and 95 percent confidence
      intervals determined using the Mantel-Haenszel method. Including the three
      highest quality studies (two randomized, one nonrandomized), there was a 34
      percent decrease in cesarean delivery rates associated with active management (OR
      0.66, 95 percent CI 0.54-0.81), without an increase in adverse neonatal outcome
      (OR for cesarean for non-reassuring fetal heart rate monitoring 0.91, 95 percent
      CI 0.68-1.22). Active management of labor is associated with a 34 percent
      decrease in the rate of cesarean delivery for dystocia in nulliparas. Along with
      the expected subsequent decrease in numbers of candidates for trials of labor,
      the decline in total cesarean deliveries over the entire population directly or
      indirectly attributable to active management is 13 percent.

PMID- 9267868
TI  - Prenatal ultrasonographic morphologic assessment of the umbilical cord: a review.
      Part I.
AB  - Our objective was to review current data pertaining to prenatal ultrasonographic
      morphology of the umbilical cord. To this goal we identified studies published in
      the English language regarding prenatal ultrasonographic morphology of this
      structure. The studies were obtained from a MEDLINE search from 1966 through May
      1997; additional sources were identified through cross-referencing. All published
      reports, case studies, and articles regarding ultrasonographic morphology of the
      umbilical cord were reviewed. Data pertaining to Doppler flow velocimetry in
      association with umbilical cord structural anomalies and umbilical cord
      compression, were also included. Review of the literature supports that prenatal
      ultrasound may outline normal anatomy or alternatively depict various congenital
      abnormalities of the umbilical cord including: cysts; pseudocysts; umbilical vein
      varix; persistent right umbilical vein; hemangiomas; umbilical vessel aneurysm
      (arterial or venous); single, hypoplastic, or fused umbilical artery; hematomas
      (spontaneous or iatrogenic); velamentous insertion; and vasa previa. The
      umbilical cord coiling index, an additional ultrasonographic morphologic feature
      may identify patients at risk for adverse perinatal outcome. Conditions of
      potential fetal compromise due to umbilical cord compression including nuchal
      cords, true knots, occult prolapse, cord presentation, fetal grasping, and cord
      entanglement in monoamniotic twins, may be detected prenatally and impaired
      umbilical flow confirmed with Doppler flow velocimetry. Ultrasound has been
      widely applied to guide invasive diagnostic and therapeutic procedures involving
      access to umbilical circulation. In conclusion, precise prenatal ultrasonographic
      depiction of the morphology of the umbilical cord may enhance perinatal
      management.

PMID- 9267870
TI  - Intracranial hemorrhage in chronic childhood ITP.

PMID- 9267869
TI  - Prenatal ultrasonographic morphologic assessment of the umbilical cord: a review.
      Part II.
AB  - Ultrasonographic assessment, although not always possible throughout the entire
      length of the umbilical cord, may assist in the diagnosis of congenital and
      functional anomalies of this structure. In such fashion, prenatal ultrasound may
      outline normal anatomy or alternatively depict various congenital abnormalities
      of the umbilical cord including: cysts; pseudocysts umbilical vein varix;
      persistent right umbilical vein; angiomyxomas; aneurysm (arterial or venous);
      single, hypoplastic or fused umbilical artery; hematomas (spontaneous or
      iatrogenic); velamentous insertion; vasa previa. The umbilical cord coiling
      index, an additional ultrasonographic morphologic feature, may identify patients
      at risk for adverse perinatal outcome. Conditions of potential fetal compromise
      due to umbilical cord compression including nuchal cords, true knots, occult
      prolapse, cord presentation, fetal grasping, and cord entanglement in
      monoamniotic twins, may be detected prenatally; and impaired umbilical flow can
      be confirmed with Doppler flow velocimetry. Ultrasound has been widely used to
      guide invasive diagnostic and therapeutic procedures involving access to
      umbilical circulation. We conclude that the review of current literature supports
      that precise prenatal ultrasonographic depiction of the morphology of the
      umbilical cord may enhance perinatal management.

PMID- 9267871
TI  - Pediatric Hematology and Oncology Department of EGE University, Izmir, Turkey.

PMID- 9267872
TI  - Retrospective analysis of 78 children with chronic idiopathic thrombocytopenic
      purpura: follow-up from 1976 to 1996.
AB  - In this retrospective study of 20 years, 78 children with chronic idiopathic
      thrombocytopenic purpura (ITP) were analyzed. Patients were followed for 1-17
      years (median 2.7 years). Every application that required therapy was accepted as
      an "attack." Seventy-eight patients received therapy in 236 attacks. Immediate
      platelet responses to high-dose methylprednisolone (HDMP), prednisone, and
      splenectomy were 69.3% (in 53 patients), 48.3% (in 35 patients), and 84.6% (in 29
      patients) of attacks, respectively. Because 31 patients were lost to follow-up,
      the rate of remission was calculated on the basis of 47 patients. The remission
      rates for patients who underwent remission spontaneously, after steroid therapy,
      and after splenectomy were 29.78, 6.38, and 14.89%, respectively. Of 78
      adolescent patients, 11.5% had intracranial hemorrhage (ICH), being after
      splenectomy. One patient died because of ICH. These data indicate that chronic
      ITP is still a serious problem during adolescence and splenectomy still seems to
      be a current choice of therapy.

PMID- 9267873
TI  - Pheochromocytoma and paraganglioma in children: a report of 24 cases of the
      French Society of Pediatric Oncology.
AB  - Pheochromocytoma and paraganglioma of childhood are rare neuroendocrine tumors.
      Urinary catecholamine measurements, metaiobenzylguanidine (MIBG) scanning,
      computed tomographic scanning, and magnetic resonance imaging have greatly
      facilitated diagnosis. Prognosis after surgical resection is excellent. In this
      retrospective series collected from French oncology centers, the risk of tumor
      progression was studied in order to assess prognostic factors and the optimal
      diagnostic and therapeutic management. Medical records of 24 children with
      paraganglioma were reviewed. This tumor occurred at a median age of 12.5 years
      and in most cases was revealed by arterial hypertension. The diagnosis was made
      by the demonstration of urinary excretion of catecholamines and their
      metabolites. Six patients had bilateral adrenal pheochromocytomas; two patients
      had extra-adrenal paragangliomas. In eight patients, the paraganglioma occurred
      as a familial disease. Surgical excision was the only therapeutic procedure. With
      a follow-up of 5.2 years, 14 of the patients are still in first complete
      remission and 6 have developed metastases or shown tumor progression. Despite a
      high long-term survival rate, the risk of malignancy and of multifocal
      involvement is of concern and is associated with a significant rate of late
      events. The outcome depends on adequacy of tumor resection and must be serially
      assessed.

PMID- 9267874
TI  - Granulopoiesis in newly diagnosed childhood solid tumors.
AB  - Granulopoiesis at the diagnosis of solid tumors has not been previously reported.
      The purpose of this study is to detect the changes of granulopoiesis of patients
      with solid tumors in different clinical stages. Granulocyte-macrophage colony
      forming unit (CFU-GM) assays and liquid suspension cultures of bone marrow and
      peripheral blood were studied in 90 children with newly diagnosed solid tumors,
      including 5 benign tumors and 85 malignant tumors. The malignant tumors were
      categorized into nonadvanced, advanced, or marrow-invaded ones. Bone marrow from
      children with immune thrombocytopenic purpura and peripheral blood from adult
      volunteers were used as controls. Granulocyte-macrophage colony formation from
      bone marrow in benign or nonadvanced malignant tumor was not significantly
      different from that of controls. However, granulocyte macrophage colony formation
      from bone marrow in advanced or marrow-invaded malignant tumor was significantly
      less than that of controls or nonadvanced malignant tumor. Furthermore, the bone
      marrow of patients with advanced malignant tumor occasionally had a defective
      proliferation pattern and the bone marrow of those with marrow-invaded malignant
      tumor often had a defective proliferation pattern. Peripheral blood in marrow
      invaded malignant tumor had colony and cluster formations in very wide ranges. As
      a malignant tumor progresses into advanced stages, irrespective of marrow
      infiltration, bone marrow CFU-GM levels may decline and defective granulopoiesis
      may occur.

PMID- 9267875
TI  - Glucocorticoid-induced apoptosis and treatment sensitivity in acute lymphoblastic
      leukemia of children.
AB  - Sensitivity of leukemic blasts to steroid therapy is one of the prognostic
      factors in acute lymphoblastic leukemia (ALL) in children. We examined the number
      of steroid receptors and the increase in the apoptotic index in peripheral blast
      cells after administration of prednisolone monotherapy in 21 children with ALL. A
      new diagnostic method was established based on determination of the apoptotic
      index in peripheral blood lymphoblasts to evaluate the steroid sensitivity of
      leukemic cells during the first day of therapy. The increase in apoptotic ratio,
      analyzed by morphologic and/or flow cytometric studies, was most expressed in the
      first 6 hours of treatment. The apoptotic ratio showed a good correlation with
      the clinical response. The number of steroid receptors (gcRs) on the blast cells
      was also examined, but it proved to be less informative than the in vivo steroid
      response itself.

PMID- 9267876
TI  - Treatment of relapsed Langerhans cell histiocytosis by cyclosporin A combined
      with etoposide and prednisone.
AB  - Optimal treatment for Langerhans cell histiocytosis (LCH) has not yet been
      established. High-risk patients with systemic LCH may have a fatal course of the
      disease despite intensive treatment. New approaches using cyclosporin A (CSA)
      showed promising results. Here, we report on a 4-year-old boy who presented with
      systemic LCH of skin, liver, bone, bone marrow, and soft tissue infiltrates. The
      patient was refractory to conventional therapy including VP16, prednisone, 6-mer
      captopurine, methotrexate, and vinblastine. Therefore the patient was treated
      with CSA as continuous therapy (serum levels were kept between 300 and 400 ng/mL)
      as well as intensification with VP16 and prednisone every 4 weeks. As early as 4
      months after starting this treatment, clinical symptoms completely disappeared
      except for a slightly enlarged liver. During the next 12 months all clinical
      symptoms except a limited skin involvement vanished although treatment with VP16
      and prednisone was stopped and CSA serum levels were kept between 100 and 150
      mg/mL. In conclusion, intensive therapy using high-dose CSA combined with VP16
      and prednisone might be a therapeutic option for patients with otherwise
      refractory LCH.

PMID- 9267877
TI  - Stage IV malignant intrapericardial germ cell tumor: a case report.
AB  - The mediastinum is a common site for germ cell tumors. We describe an unusual
      case in an 18-month-old girl who presented with respiratory distress and
      cardiomegaly. An echocardiogram revealed a large pericardial effusion and a mass
      adjacent to the heart. She underwent detailed investigation and at open
      exploration was found to have a wholly intrapericardial malignant yolk sac tumor.
      Staging investigations revealed a bony metastasis. The serum marker alpha
      fetoprotein was elevated. She was treated with chemotherapy and is in remission 1
      year after completion of treatment. We review the methods of diagnosis and follow
      up of children with these tumors.

PMID- 9267878
TI  - Portal vein thrombosis in a 17-year-old female adolescent with essential
      thrombocytosis.
AB  - A 17-year-old girl known to suffer from essential thrombocytosis (ET) was
      admitted with severe abdominal pain that was due to sonographically verified
      portal and hepatic vein thrombosis. ET is a well-documented disease and portal
      vein thrombosis has often been reported in adults but not in children and
      adolescents suffering from ET. Coincidence of ET, urinary tract infection, oral
      contraception, and cessation of acetylsalicylic acid therapy might be responsible
      for the early manifestation of portal and hepatic vein thrombosis in our patient.

PMID- 9267879
TI  - Multiple hepatoblastomas associated with trisomy 18 in a 3-year-old girl.
AB  - A very rare case of full trisomy 18 associated with multiple hepatoblastomas is
      reported. The patient also had ventricular septal defect and patent ductus
      arteriosus, which were repaired at 6 months of age. After the cardiac surgery,
      she was noted to have an abdominal mass and an elevated serum alpha-fetoprotein
      level. A partial hepatic lobectomy was performed at 7 months of age, and the
      resected tumor was diagnosed as a fetal-type hepatoblastoma. At 2 years and 4
      months of age, a chest radiography disclosed an elevated left diaphragm, and
      abdominal ultrasonography demonstrated a tumor in the left hepatic lobe. The
      resected tumor was also diagnosed as a fetal-type hepatoblastoma. Chromosomal
      analysis demonstrated that the karyotypes of peripheral blood and hepatic tumor
      cell obtained on two occasions were both 47,XX, +18. She has no evidence of
      recurrence at 3 years of age without specific therapy.

PMID- 9267880
TI  - Cryptococcal meningitis following a thrombotic microangiopathy in an unrelated
      donor bone marrow transplant recipient.
AB  - In patients undergoing bone marrow transplantation cryptococcosis is rarely
      encountered. We report a fatal case of Cryptococcus meningitis in a 12-year-old
      girl with acute lymphoblastic leukemia (ALL) in second remission who had a
      transplant from a human leukocyte antigen (HLA)-identical unrelated bone marrow
      donor. The conditioning regimen was thiotepa, cyclophosphamide, and total body
      irradiation (TBI); graft-versus-host disease (GVHD) prophylaxis consisted of
      cyclosporin A, methotrexate, and antilymphocyte globulin (ALG). The patient
      experienced stage III GVHD responsive to high-dose corticosteroids. On day +54 a
      thrombotic microangiopathy occurred. On day +64 neurological status worsened; a
      brain computed tomographic (CT) scan showed hyperdense lesions suggesting fungal
      infection. Detection of cryptococcal antigen by latex agglutination was positive
      but India ink stain and culture were negative. Despite treatment with
      amphotericin B, 5-flucytosine, and granulocyte-macrophage colony-stimulating
      factor, the patient died 13 days after the diagnosis.

PMID- 9267881
TI  - Pleuropulmonary blastoma of the lung presenting as posterior mediastinal mass: a
      case report.
AB  - Pulmonary blastoma is a rare primary neoplasm of the lung. A case of a 2 1/2-year
      old girl with a rapidly progressing pleuropulmonary blastoma clinically
      presenting as a posterior mediastinal mass is discussed.

PMID- 9267882
TI  - Clinical and hematological remission after a single dose of mitoxantrone in a
      child with Philadelphia chromosome-positive chronic myeloid leukemia.

PMID- 9267883
TI  - High-dose intravenous immunoglobulin as single therapy in a child with autoimmune
      hemolytic anemia.

PMID- 9267884
TI  - Late relapse in a patient with acute lymphoblastic leukemia thirteen years after
      diagnosis.

PMID- 9267885
TI  - Glutathione as a cytoprotective antioxidant in erythrocytes of the newborn: the
      role of G6PD and zinc protoporphyrin: a hypothesis.

PMID- 9267886
TI  - Primary intracranial germ cell tumors: clinicopathologic review of 32 cases.
AB  - Primary intracranial germ cell neoplasms are rare tumors and constitute a
      heterogeneous group. We have reviewed 32 cases, over a 21-year period, from the
      University of Florida. The cases include 22 germinomas, 6 mixed germ cell tumors,
      and 4 teratomas. The clinical presentations in these cases were more closely
      related to the location of the tumor, that is, pineal or suprasellar, rather than
      the histologic subtype. Neuroimaging evaluation was useful in distinguishing
      between germinomas, teratomas, and other mixed germ cell tumors (MGCTs),
      primarily by evaluation of cystic versus solid lesions (teratoma versus
      germinoma), contents of cysts (teratoma versus MGCT), and infiltrative nature of
      the tumors (MGCT), although cytologic-histopathologic confirmation remains
      necessary. Germinomas responded favorably to radiation therapy with survival
      periods of over 16 years; MGCTs were treated with combination chemotherapy and
      radiation, with a markedly poorer prognosis. This study underlines the critical
      significance of histopathologic evaluation of the tumor in determining
      therapeutic interventions as well as prognosis.

PMID- 9267887
TI  - Quantitative histologic factors for grouping childhood supratentorial neuroglial
      tumors.
AB  - The histologic heterogeneity of childhood supratentorial neuroglial tumors, when
      quantified, identifies relatively homogeneous subgroups for prognostic purposes
      and for assignment in clinical trials. Our sample consisted of supratentorial
      tumors in the Childhood Brain Tumor Consortium. The data consist of reliably
      identified histologic features and demographic, clinical, operative, and survival
      information. Factor analysis was used to identify uncorrelated "factors," each
      represented by a different combination of histologic features in 703 tumors. The
      defining histologic features were used to label each factor. The heterogeneity of
      each tumor was summarized using the factor scores for each factor. We compared
      the survival estimates of subgroups of tumors within common diagnostic classes.
      We identified five uncorrelated quantitative factors that accounted for much of
      the histologic variation. Our factor labels were Jumbo, Fibrillary,
      Proliferative, Spongy, an Oligodendroglial. Two thirds of tumors had high scores
      on two or more factors, indicating a high degree of heterogeneity among these
      tumors. Eighty-four percent of supratentorial tumors were accounted for by 19
      nonoverlapping relatively homogeneous histologic groups. The five quantitative
      factors complement standard qualitative taxonomies by summarizing more completely
      the histologic feature aspects of a tumor than by diagnosis alone and quantify
      the histologic heterogeneity of individual tumors. Histologically homogeneous
      groups of tumors are essential for clinical trials, biologic research, and
      prognostic models.

PMID- 9267888
TI  - Prognosis for children with supratentorial neuroglial tumors.
AB  - Factor analysis of reliably identified histologic features in supratentorial
      glial tumors yielded five interpretable "factors": Spongy, Fibrillary,
      Proliferative, Jumbo, and Oligodendroglial. Quantitative scores can be calculated
      for each factor in a tumor to summarize its heterogeneity. The objective was to
      investigate whether factor scores are useful for prognostic purposes. The sample
      consisted of 703 children with supratentorial neuroglial tumors with factor
      scores for each of the five factors. Data were based on the presence or absence
      of 26 reliably identified histologic features, plus clinical and survival
      information. Multivariate proportional hazards models assessed each factor's
      contribution to survival for children who survived 1 month after operation (n =
      609). Patient-specific clinical data were allowed in the models. Increased
      likelihood of survival is associated with greater tumor removal, later decade of
      surgery, and high Spongy and high Oligodendroglial factor scores. Decreased
      likelihood of survival is associated with high Proliferative factor scores and
      radiation and/or chemotherapy treatment. Gender, age, location, and Jumbo and
      Fibrillary factor scores did not provide additional prognostic information. Three
      reliable histologic features, nondefining for any histologic factor, added
      prognostic information: Rosenthal fibers and glomeruli are associated with
      improved prognosis; pleomorphic nuclei are associated with worse prognosis. A
      high Oligodendroglial factor score is associated with a worse prognosis for some
      classes of astrocytoma but with a better prognosis for oligodendroglial tumors. A
      high Proliferative score is associated with a worse prognosis for anaplastic
      astrocytomas, ependymomas, and unclassifiable tumors. A high Spongy score is
      associated with a better prognosis for anaplastic astrocytomas but with a worse
      prognosis for pilocytic astrocytomas. For giant cell astrocytomas,
      gangliogliomas, and miscellaneous tumors, none of the factors is prognostic.
      Spongy, Oligodendroglial, and Proliferative factors provide important prognostic
      information for children with supratentorial neuroglial tumors.

PMID- 9267889
TI  - Langerhans cell histiocytosis of lymph nodes: a morphological assessment of 43
      biopsies.
AB  - The morphology of Langerhans cell histiocytosis (LCH) involving lymph nodes was
      analyzed in 43 biopsies from 39 patients and findings were correlated with
      clinical data. Five histological motifs were recognized: sinusoidal, limited
      sinusoidal, epithelioid granulomatous, partial effacement, and total effacement.
      Lesions were composed of histiocytes of the Langerhans cell (LC) family,
      macrophages, multinucleated giant histiocytes, T lymphocytes, and eosinophils in
      varying proportions. Proliferative fractions ranged from 2.6 to 48% and 2 of 25
      specimens showed a hyperdiploid aneuploid DNA ploidy profile. Epithelioid
      granulomas composed of histiocytes with the LC phenotype dominated three
      abdominal specimens, reflecting a picture of LCH not previously reported. Total
      effacement seen in three patients, was associated with unmarked histiocytoid
      cells, high proliferative fraction, aneuploid DNA ploidy profile, and, in two, a
      fatal outcome. Different histologic appearances in lesions from separate sites of
      the same patient were seen in the cases with epithelioid granulomas and in those
      with total effacement. The diverse histopathology in lymph nodes involved by LCH
      is considered in the context of current knowledge of this enigmatic disease.

PMID- 9267890
TI  - Morphometric analysis of pulmonary development in the sheep following creation of
      fetal diaphragmatic hernia.
AB  - Congenital diaphragmatic hernia (CDH) in humans is relatively common and
      associated with high mortality attributed mainly to pulmonary hypoplasia.
      Previous animal models have induced CDH late in gestation, in contrast to the
      human situation, and only limited morphometric analyses have been reported. We
      undertook early surgical creation of CDH in fetal lambs, days 72-74 of gestation
      (n = 8), with unoperated lambs (n = 8) as controls. At 143 days (term = 145-149)
      a cesarean section was performed and the lungs were obtained, inflation fixed,
      divided into lobes, and processed for morphometry. In the CDH group the total
      lung volumes (51.3 mL compared to 223.8 mL) and gas exchange surface areas (5.85
      m2 versus 26.43 m2) were less than one quarter of control values. Capillary
      loading was reduced from 0.3 mL/m2 in controls to 0.12 mL/m2 in CDH and
      parenchymal volume reduced from 77% in controls to 57% in CDH. Within parenchyma,
      gas exchange tissue volume was increased in CDH (66%) compared with controls
      (50%). CDH lungs had primitive air sacs/alveoli that were smaller (perimeter 83
      microns) and more numerous (1321 per mm2) than in controls (perimeter 132
      microns, 504 per mm2). The left lung and left upper lobe were affected most.
      Induction of CDH in the lamb at this early age results in quantifiable,
      reproducible pulmonary hypoplasia from which comparisons can be made with the
      human condition.

PMID- 9267891
TI  - Quantitative histologic factors for grouping childhood infratentorial neuroglial
      tumors.
AB  - We employed factors analysis to quantify the degree of histologic heterogeneity
      of childhood infratentorial neuroglial tumors. Our data were 26 reliably
      ascertained histologic features in 1068 children in the Childhood Brain Tumor
      Consortium database. The factor analysis identified five uncorrelated
      quantitative "factors," each derived from a different linear combination of the
      26 histologic features, that accounted for much of the histologic variation.
      Histologic features differed in their importance in each factor. The most
      important features in each factor were used for naming using simple, histologic,
      familiar descriptive terms: Spongy, Proliferative, Ring, Fibrillary, and Nuclear.
      Each tumor has a score on each factor. Two-thirds of tumors had high scores for
      at least two factors, indicating frequent histologic heterogeneity among these
      tumors. Ninety-five percent of tumors were allocated to 1 of 11 nonoverlapping
      histologically homogeneous groups. The five quantitative factors complement
      standard qualitative taxonomies by making explicit the histologic heterogeneity
      or homogeneity of individual tumors and provide the pathologist with a method
      that takes advantage of more of the histology of each tumor than conventional
      nomenclatures. Histologically homogeneous groups of tumors are likely to be of
      value in clinical trials and biologic research. Prognostic models based on these
      factors have been published.

PMID- 9267892
TI  - Amniotic fluid and maternal serum levels of CA125 in pregnancies affected by Down
      syndrome: a re-evaluation of the role of CA125 in Down syndrome screening.
AB  - In a study of amniotic fluid from 91 Down syndrome cases and 240 controls, we
      have shown that the median value of CA125 in pregnancies affected by Down
      syndrome on the whole reflects those observed in the maternal serum from 106
      affected cases and 238 controls. The median MOM for CA125 in amniotic fluid from
      Down syndrome pregnancies was 1.04 and in maternal serum 1.06, neither value
      being significantly different from that for the control population. We confirm
      our previous observation that CA125 is not a marker of Down syndrome and conclude
      that CA125 has no role to play in Down syndrome screening.

PMID- 9267893
TI  - Comparison of Down's syndrome screening strategies in Asians combining serum free
      beta-hCG and alpha-fetoprotein with maternal age.
AB  - High free beta human chorionic gonadotropin (beta-hCG) and low alpha-fetoprotein
      (AFP) levels were found in 47 Asian Down's syndrome pregnancies (median values
      2.79 and 0.77 MOM, respectively). At a 5 per cent false-positive rate, free beta
      hCG alone would identify 46.8 per cent of Down's syndrome pregnancies, age alone
      detected 34.5 per cent of affected cases, whilst AFP alone detected 17 per cent
      and free beta-hCG/AFP MOM ratios detected 48.9 per cent of Down's syndrome cases.
      When combined with maternal age-specific risk, free beta-hCG could achieve a 59.6
      per cent detection rate, with AFP achieving 42.6 per cent, free beta-hCG/AFP MOM
      ratios 61.7 per cent, and combined free beta-hCG and AFP a detection rate of 63.8
      per cent for a 5 per cent false-positive rate. Down's syndrome screening at an
      early gestational age (before 18 weeks) could achieve a 68 per cent detection
      rate with a 5 per cent false-positive rate, compared with a 59.1 per cent
      detection rate for a 5.2 per cent false-positive rate when screening at a late
      gestational age. The use of free beta-hCG in Down's syndrome screening programmes
      can yield an improved efficacy in the detection of Down's syndrome in an Asian
      population.

PMID- 9267894
TI  - A demographic approach to the assessment of Down syndrome screening performance.
AB  - The aim of this article is to examine the performance of screening for fetal Down
      syndrome (DS) in the context of demographic variation in time and place, using
      population and fertility data for several European countries. Two screening
      approaches are distinguished: one on the basis of maternal serum screening with
      human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP) in combination
      with maternal age, and one on the basis of maternal age only. Screening
      performance, as measured by detection and false-positive ratios, is shown to be
      the result of the screening approach chosen and of the demographic
      characteristics of the population under consideration. A proper distinction
      between these two determinants of DS screening performance should be made, in
      order to distinguish between an improvement in screening performance that is
      brought about by a new screening approach and an improvement that is brought
      about by demographic change. We recommend that measures of DS screening
      performance be standardized for demographic variation. The methodology and
      demographic data presented in this article can be used for this purpose.

PMID- 9267895
TI  - Rapid mid-trimester prenatal diagnosis of beta-thalassaemia and other
      haemoglobinopathies using a non-radioactive anion exchange HPLC technique--an
      Indian experience.
AB  - Anion exchange high performance liquid chromatography (AX-HPLC) has been widely
      used for separating and quantifying various haemoglobin fractions especially in
      the haemoglobinopathies. We have evaluated the reliability of this technique to
      measure low concentrations of adult haemoglobin (HbA) in fetal blood to enable
      differentiation between affected and unaffected fetuses at risk for beta
      thalassaemia (85) and other haemoglobinopathies such as delta beta/beta
      thalassaemia (1), E-beta-thalassaemia (2), S-beta-thalassaemia (1), and sickle
      cell anaemia (1). The HbA values obtained ranged between 0 and 9.51 per cent. The
      HbA for 27 affected fetuses was 0 per cent, while two showed a HbA value of 0.5
      per cent. The mean HbA for 61 unaffected fetuses was 4.8 +/- 2.08 per cent.
      Thirty cord blood samples (cord abortus in cases of affected fetuses and cord
      full term in cases of unaffected fetuses) were analysed to reconfirm the
      diagnosis. Ten babies between 8 and 18 months of age could be followed up for
      confirmation. AX-HPLC was found to be a simple and rapid procedure with high
      sensitivity and there was a good correlation between the HbA values obtained by
      AX-HPLC and the diagnosis by carboxymethyl cellulose (CMC) chromatography.

PMID- 9267896
TI  - The risk of alpha-thalassaemia in offspring of beta-thalassaemia carriers in Hong
      Kong.
AB  - Couples in whom one is heterozygous for alpha-thalassaemia-1 and the other is
      heterozygous for beta-thalassaemia are assumed not to be at risk of having
      offspring with homozygous alpha-thalassaemia-1 or homozygous beta-thalassaemia.
      We retrospectively reviewed the genetic outcome of 189 pregnancies of 178 couples
      in whom the partners were diagnosed to be discordant heterozygotes of alpha
      thalassaemia and beta-thalassaemia on haematological tests. Zeta gene mapping was
      performed on 158 beta-thalassaemia carriers to diagnose the presence of co
      existing alpha-thalassaemia-1. Eleven patients (7 per cent) were found to be
      compound alpha- and beta-thalassaemia heterozygotes. They accounted for 16
      pregnancies, of which five were diagnosed to be affected by homozygous alpha
      thalassaemia-1. Our results show that couples presumed to be discordant
      heterozygotes of alpha- and beta-thalassaemia on haematological testing are at
      risk of having offspring with homozygous alpha-thalassaemia-1 if the zeta gene
      mapping of the heterozygous beta-thalassaemia partner shows co-inheritance of
      alpha-thalassaemia-1. Prenatal diagnosis of homozygous alpha-thalassaemia-1
      should be performed on these at-risk pregnancies.

PMID- 9267897
TI  - Reproductive behaviour of couples at risk for sickle cell disease in Cuba: a
      follow-up study.
AB  - Three hundred and forty-three Cuban women at risk of having children with sickle
      cell anaemia or sickle cell-haemoglobin C disease were interviewed 2-8 years
      after the index pregnancy (that in which their risk was detected). The aim was to
      collect information on their attitude towards prenatal diagnosis in subsequent
      pregnancies. Twenty-two per cent (75/343) had dissolved their marriage and 9 per
      cent of these (7/75) considered that their at-risk status had influenced the
      separation. Sixty-three per cent of stable couples at risk (168/268) had decided
      to have no further children; 27 per cent of these (45/168) were afraid of having
      an affected child and 4 per cent (7/168) were afraid of the obstetric procedure.
      Nineteen per cent of the stable couples at risk (52/268) had had at least one
      further child or pregnancy. Of these, 44 per cent (23/52) requested prenatal
      diagnosis early and spontaneously, and a further 44 per cent (23/52) requested
      prenatal diagnosis but after re-identification by screening and recounselling.
      Only 12 per cent (6/52) did not request prenatal diagnosis. Attitude towards
      prenatal diagnosis was most positive among more educated women. The general
      perception of the prevention programme was good.

PMID- 9267898
TI  - The proportion of fetal nucleated red blood cells in maternal blood: estimation
      by FACS analysis.
AB  - The purpose of this study was to determine the proportion of fetal nucleated red
      blood cells (NRBCs) among enriched NRBCs and to evaluate the effectiveness of
      enriching NRBCs in maternal blood using fluorescence-activated cell sorting
      (FACS) to separate NRBCs. The origin of enriched NRBCs was determined using
      fluorescence in situ hybridization (FISH) methods. Y-specific signals were
      observed in 4.6 +/- 1.5 per cent of the enriched cells from 14 of 16 (87.5 per
      cent) pregnant women who gave birth to boys. In this series, the specificity of
      the fetal sex diagnosis was 100 per cent, the sensitivity 88 per cent, and the
      negative predictive value 86 per cent. Fetal NRBCs are present in maternal blood
      and FACS has the potential to enrich fetal NRBCs. Fetal cells were estimated to
      be enriched more than 10,000-fold in the first trimester and more than 100-fold
      in the third trimester. Average frequencies of fetal cells in maternal blood were
      8.1 x 10(-5) and 1.6 x 10(-5) in the first trimester and the second/third
      trimesters. However, most of the NRBCs in maternal blood are maternal in origin.

PMID- 9267899
TI  - Screening for fetal anomalies in the 12th week of pregnancy by transvaginal
      sonography in an unselected population.
AB  - The advantages and limitations of transvaginal (TV) sonography in detecting fetal
      anomalies in the 12th week of pregnancy were examined in a prospective screening
      study of an unselected population. During a 3-year period, 3991 examinations were
      performed and 35 fetuses were identified as having 43 anomalies (0.9 per cent).
      Most of these malformations were either severe structural disorders or isolated
      nuchal changes when karyotyping revealed chromosomal aberration in six cases.
      Twenty-one pregnancies were terminated and three fetuses died. Routine
      transabdominal (TA) ultrasonographic examinations were performed at 18 and 30
      weeks in all those pregnancies where the TV scan had not found fetal anomalies.
      TA sonography identified 19 abnormal fetuses and ten cases remained undetected.
      TV sonography detected 51 per cent of malformed fetuses which were diagnosed
      prenatally (not including cases with nuchal oedema) and 41 per cent of the total
      were found in this study. Besides offering the possibility of early termination,
      first trimester screening has the advantage of identifying a transient
      sonographic sign, nuchal oedema, which can be used as a marker in screening for
      fetal chromosomal abnormalities. However, standard mid-second-trimester TA
      scanning is still recommended, since a significant number of malformations cannot
      be detected so early in pregnancy.

PMID- 9267900
TI  - Prenatal diagnosis of supernumerary chromosome derivative (22) due to maternal
      balanced translocation in association with diaphragmatic hernia: a case report.
AB  - An aneuploid fetus was detected prenatally by cordocentesis at 27 weeks'
      gestation following ultrasonographic diagnosis of severe fetal growth retardation
      and a large diaphragmatic hernia. The fetal karyotype was revealed to be
      47,XX,der(22)t(11;22)(q23.3;q11.2) after parental bloods confirmed a balanced
      reciprocal translocation in the mother. Approximately 85 cases with an unbalanced
      karyotype 47,XX(or XY),+der(22),t(11;22) due to 3:1 meiotic disjunction in the
      parental translocation carrier have been reported in the world literature and
      only one of them was diagnosed prenatally. This is the first detailed case report
      of a supernumerary derivative (22) chromosome abnormality diagnosed prenatally in
      association with diaphragmatic hernia.

PMID- 9267901
TI  - Prenatal ultrasound findings in a fetus diagnosed with Gaucher's disease (type 2)
      at birth.
AB  - A 26-year-old woman with no significant history was found to have a fetus with
      hepatosplenomegaly and neurological abnormalities in utero on ultrasound. The
      baby was found to have a severe clinical manifestation of type 2 Gaucher's
      disease.

PMID- 9267902
TI  - Prenatal sonographic diagnosis of cleidocranial dysostosis.
AB  - Cleidocranial dysostosis is an autosomal dominant disorder characterized by
      absence or hypoplasia of the clavicles, skull abnormalities, and abnormal
      dentition. The prenatal diagnosis of this condition has been reported once
      previously in a known high-risk pregnancy. In this report we describe the
      prenatal findings of cleidocranial dysostosis at 19 weeks' gestation in a woman
      affected with this disorder but undiagnosed before the fetal scan. This report is
      unique in the sense that an autosomal dominant condition diagnosed in the fetus
      led to a similar diagnosis in the mother.

PMID- 9267903
TI  - Recurrent severe infantile cortical hyperostosis (Caffey disease) in siblings.
AB  - Infantile cortical hyperostosis (ICH), Caffey disease, is a multifocal,
      inflammatory skeletal process with classic onset before the fifth month of life
      and resolution by the age of 3 years. A severe phenotype with early prenatal
      onset has also been described. Inheritance is generally accepted a autosomal
      dominant with variable expression and penetrance. However, occurrence in siblings
      with no family history has been reported, raising the possibility of
      heterogeneity and the existence of a severe autosomal recessive form. We describe
      a third family with prenatally diagnosed ICH in two siblings, providing further
      evidence for this form of inheritance.

PMID- 9267904
TI  - Severe fetal malformations associated with trisomy 16 confined to the placenta.
AB  - Chorionic villus sampling (CVS) and amniocentesis were performed on a pregnant
      woman during her 24th week of amenorrhoea following an ultrasound scan which
      showed a fetus with hydrocephaly, intrauterine growth retardation (IUGR), and a
      single umbilical artery. The direct karyotype from the cytotrophoblast was non
      mosaic 47,XXX,+16, while in amniotic fluid and several fetal tissues, studied
      post-mortem, a normal 46,XX karyotype was found in more than 400 cells.
      Uniparental disomy (UPD) was excluded by molecular genetic studies. Autopsy
      confirmed the echographic findings; in addition, agenesis of the corpus callosum
      and polysplenia were observed. This is the second example of congenital
      abnormality associated with confined placental mosaicism (CPM) for trisomy 16,
      without evidence of either UPD or an apparent contribution of abnormal cells to
      the fetus.

PMID- 9267905
TI  - Prospective prenatal diagnosis of Prader-Willi syndrome due to maternal disomy
      for chromosome 15 following trisomic zygote rescue.
AB  - We present a prenatal predictive diagnosis of Prader-Willi syndrome arising as a
      result of maternal heterodisomy for chromosome 15. The diagnosis arose following
      chorionic villus sampling which showed a mosaic trisomy 15 karyotype with a
      chromosomally normal follow-up amninocentesis. Molecular studies on DNA extracted
      from cultured amniocytes showed no evidence of a paternal allele at two widely
      separated loci and this was taken as evidence of maternal disomy predictive of
      Prader-Willi syndrome in the fetus.

PMID- 9267906
TI  - Isolated choroid plexus cysts and aneuploidy.

PMID- 9267907
TI  - Nuchal translucency screening for chromosomal abnormalities in a routine
      ultrasound practice.

PMID- 9267908
TI  - Cordocentesis using the combined technique.

PMID- 9267910
TI  - Current awareness in prenatal diagnosis.

PMID- 9267909
TI  - Limb defects as a consequence of CVS or uterine lavage? A need for further
      documentation of the technique and complications.

PMID- 9267911
TI  - Neuropsychological aspects of the rehabilitation of patients with paralysis from
      a spinal injury who also have a brain injury.
AB  - In order to examine the rehabilitation process of patients suffering from a
      severe spinal cord injury and who also have a cerebral injury, 322 patients with
      paralysis from a spinal injury were subjected to neuro-psychiatric and neuro
      psychological examinations. On average 20.2% of these patients showed an
      associated cerebral lesion. The psychological results of such cerebral lesions
      are summarized under the concept of the co-called organic psychic syndrome (OPS).
      In 27.7% of these patients no organic psychic syndrome resulted, and in these
      patients a conventional paralysis rehabilitation could be carried out. 41.6%
      showed very minor to moderate injuries, with 30.7% being severely disabled from
      the cerebral injury. Rehabilitation for these patients was modified, using new
      therapeutic approaches, and also traditional therapeutic methods adapted to the
      abilities and needs of this patient group. In 25.5% of the patients there was no
      substantial improvement during the treatment period of initial rehabilitation (x
      = 12.5 weeks for the treatment of cerebral injury); but in 36.2% of the patients
      there was substantial improvement and in 38.3% full remission of organic psychic
      disorders occurred. Improvements in this sphere have a direct bearing on the
      rehabilitation capacity of this patient group.

PMID- 9267912
TI  - Investigation of the social status of paraplegic individuals after medical
      rehabilitation.
AB  - The social services of the German centres for spinal cord injuries compiled
      social data on 2000 recently injured paraplegics. The aim of the study was to
      determine whether and to what extent patients had been reintegrated to jobs after
      completion of physical rehabilitation treatment. A 31-point questionnaire
      surveyed all relevant data pertaining to the projected professional vita. The
      results for the medically rehabilitated population (n = 651) indicate that 45%
      returned to their previous job, school or college. Intensified use of computers
      and advanced academic backgrounds of afflicted individuals contribute to a higher
      chance for reintegration at a previous job. Our social statistics also include
      data on living conditions and social support. Household caretaking support is
      offered by family members in 73% of cases, while 5% permanently live in nursing
      homes.

PMID- 9267913
TI  - Clinical Case of the Month: Urology. urinary incontinence in a male paraparetic
      patient (able to walk) with a mixed lower motor neuron lesion.

PMID- 9267914
TI  - Postpolio syndrome: a 5 year follow-up.
AB  - The purpose of this investigation was to study subjective symptoms, medical and
      social situation, pulmonary function and physical work capacity during a period
      of 3-5 years in patients with the postpolio syndrome. We evaluated 68 patients
      consecutively admitted to our hospital because of postpolio syndrome, and re
      evaluated 63 of the same patients 3-5 years later, 43 women and 20 men with mean
      age 55 +/- 10 (1 SD) years at the second evaluation. The patients answered a
      questionnaire about their subjective symptoms and medical and social situation,
      and underwent spirometry as well as symptom-limited exercise stress testing. Most
      patients experienced increasing symptoms and physical disability related to their
      polio, while the majority reported that their mental health were unchanged or
      improved. The lung function was in average moderately reduced of restrictive
      type, and only minor changes were found during the 3-5 years. A pronounced
      reduction in peak oxygen uptake was seen at the first evaluation, especially in
      women. At the second examination, peak oxygen uptake was further decreased,
      especially in men, more than predicted from increasing age. The patients
      increased their body mass index significantly during the same period. These
      results indicate that subjective symptoms and physical disability related to
      polio increased with increasing age in these patients with the post-polio
      syndrome, and cardiorespiratory deconditioning and weight gain also became
      increasing problems in most patients. However, the mental status of the patients
      remained stable or improved, possibly due to our comprehensive re-rehabilitation
      and educational programme.

PMID- 9267915
TI  - Prevention of spinal cord injuries that occur in swimming pools.
AB  - The purpose of this study was to determine the usual circumstances surrounding
      spinal cord injuries that occur in swimming pools so that appropriate primary
      prevention programs targeted at high risk persons, activities, and environments
      could be developed and initiated. A sample of 341 persons enrolled in the
      National Spinal Cord Injury Statistical Center database since 1973 whose injury
      was the result of a swimming pool mishap was identified. Medical records were
      reviewed retrospectively and a survey questionnaire was administered by telephone
      to 196 persons (57.5%) who were located and agreed to participate. Average age at
      time of injury was 24 years, 86% of injured persons were men, 95% were white, 70%
      were never married, 32% had less than a high school education, and only 7% were
      college graduates. Almost all injuries (87%) occurred in private/residential
      pools. Most injuries (57%) occurred when diving into less than 4 feet of water,
      while an additional 38% occurred at water depths between 4 and 8 feet. Depth
      indicators were not present in 75% of cases. There were no warning signs posted
      in 87% of cases. There was no lifeguard on duty in 94% of cases. There was self
      reported alcohol involvement in 49% of cases, but drugs were involved in only 2%
      of cases. Almost half of all injuries (46%) occurred during parties. In 44% of
      cases, the injury occurred during the person's first visit to that particular
      pool. Ordinary dives accounted for 70% of cases, followed by unusual dives (17%),
      unintentional pushes (6%), and other circumstances (7%). Almost all injuries
      (88%) occurred between 1 pm and 1 am with the most frequent time of day being 6
      pm, and 82% occurred during June, July or August. Over half (51%) of all injuries
      occurred on Saturday or Sunday. These results provide important clues to the
      development of a successful primary prevention program.

PMID- 9267916
TI  - Psychological investigation of spinal cord injury patients.
AB  - Spinal cord injuries (SCI) often have psychological consequences, primarily
      anxiety and depression, which may interfere with rehabilitation possibilities,
      with adjustment to the impairment and therefore with the possibility of returning
      to previous familiar social life and work. To assess the degree of anxiety and
      depression in SCI patients, and to study the factors contributing to their
      genesis, 100 SCI in- and out-patients were administered questionnaires for self
      rating anxiety and depression. A group of newly injured patients was followed up
      for a year after their discharge to study the evolution of the two psychological
      syndromes. These two psychological pathologies in SCI patients were respectively
      13% (anxiety) and 16% (depression). Some characteristics were significantly
      associated with a higher risk of developing psychological distress: the presence
      of severe complications, the lack of autonomy, and low educational level. We did
      not observe any modification of the psychological picture over time. The lack of
      reduction in anxiety and depression over time could mean that the two pathologies
      are maintained by the obstacles SCI patients meet every day resulting from their
      neurological deficit. Our data justify the provision of psychological services
      for SCI patients in the rehabilitation centres; these services should still be
      available to the patients even after discharge.

PMID- 9267917
TI  - Urinary catheter blockage depends on urine pH, calcium and rate of flow.
AB  - Urinary catheters tend to block when biofilm from urease-producing organisms
      build up on the catheter surface. This is a locally-occurring process that
      influences and influenced by the composition of the urine. In this work we relate
      urine pH and calcium to catheter blockage and suggest how to reduce the rate of
      encrustation. Sixty patients with indwelling urinary catheters were studied, 26
      of them being troubled by frequent blockage of their catheters, 34 of them not. A
      series of small urine samples were collected during a 24 h period. Urinary pH and
      calcium concentration were combined into discriminant functions designed to
      separate Blockers from Non-blockers and achieved a 95% correct classification.
      The results indicate that a high and uniform rate of fluid intake is mandatory
      for the patient with a tendency for catheter blockage. Excessive total fluid
      intake may be avoided by attention to uniformity. Other avoidable risk factors
      include: excess dietary calcium from certain protein supplements and antacids;
      excess dietary magnesium from certain beverages and antacids; alkali from
      effervescent tablets; excess dietary citrate from some fruit juices and cordials;
      intermittent dehydration from alcohol ingestion. Less tractable risk factors
      include infection of the urinary tract with urease-positive organisms,
      hypercalciuria of immobilisation, hyperhydrosis and postural oliguria. The
      processes involved in catheter encrustation and blockage provide a model for the
      formation of calculi in spinal cord injured patients. Therefore the above
      considerations may also be relevant to the management of stone disease in
      paraplegic and tetraplegic patients.

PMID- 9267918
TI  - Relationship between surgery and pain following spinal cord injury.
AB  - Pain is a significant problem following spinal cord injury (SCI) and has a major
      influence on quality of life and the ability to engage in rehabilitation. Surgery
      is often indicated in the management of spinal cord injury to stabilise the spine
      and prevent further neurological deficit. However, the relationship between
      surgical intervention and the presence of pain following SCI is unclear. We
      performed a prospective, longitudinal study of 100 individuals with traumatic SCI
      to determine the prevalence of different types of SCI pain at 2, 4, 8, 13, 26 and
      52 weeks following SCI and to determine whether there was a relationship between
      surgical intervention and the presence or absence of specific types of SCI pain.
      We found that surgical intervention was associated with a significantly higher
      prevalence of musculoskeletal pain at 2 weeks but not at 4, 8, 13, 26 and 52
      weeks following injury, when compared with those who did not have surgery. There
      were no significant differences in the prevalence of visceral, neuropathic at
      level or neuropathic below level pain in the surgical and non-surgical groups at
      any stage. The results from this study suggest that apart from an increased
      prevalence of musculoskeletal pain at 2 weeks following SCI in those who undergo
      surgery, there is no significant relationship between surgical intervention and
      the presence of SCI pain.

PMID- 9267919
TI  - Traumatic spinal cord injuries in southeast Turkey: an epidemiological study.
AB  - In 1994, a retrospective study of new cases of traumatic Spinal Cord Injury (SCI)
      was conducted in all the hospitals in Southeast Turkey: 75 new traumatic SCI were
      identified. The estimated annual incidence was 16.9 per million population. The
      male/female ratio was 5.8/1. The mean age was 31.3, being 31.25 for male patients
      and 31.36 for female patients. 70.7% of all patients were under the age of 40.
      The major causes of SCI were falls (37.3%) and gunshot wounds (29.3%), followed
      by car accidents (25.3%), and stab wounds (1.3%). Thirty one patients (41.3%)
      were tetraplegic and 44 (58.7%) paraplegic. In tetraplegic patients the commonest
      level was C5, in those with paraplegia L1. The commonest associated injury was
      head trauma followed by fractures of the extremity(ies). Severe head trauma,
      being a major cause of death, may have obscured the actual incidence of SCI. Most
      of gunshot injured SCI patients were young soldiers fighting against the rebels.
      As there was no available data for the rebels with SCI, the actual incidence of
      SCI in Southeast (SE) Turkey should be higher than that found in this study.

PMID- 9267920
TI  - Limited vs full microbiological investigation for the management of symptomatic
      polymicrobial urinary tract infection in adult spinal cord-injured patients.
AB  - Spinal cord-injured (SCI) patients often suffer from symptomatic polymicrobial
      urinary tract infection (UTI). The objective of this study was to evaluate the
      clinical outcome and cost-savings associated with antibiotic therapy based on
      limited vs full microbiological investigation of urine cultures in adult SCI
      patients with symptomatic polymicrobial UTI (> or = 2 organisms growing in urine
      cultures). In the first part of the study, a total of 40 evaluable patients were
      prospectively randomized in a single-blinded fashion to receive antibiotic
      therapy based on either limited (21 patients) or full microbiologic investigation
      (19 patients) of urine cultures. The practicality of a limited microbiological
      investigation was further examined in the second part of the study where 12
      consecutive patients with symptomatic polymicrobial UTI initially had only
      limited microbiological investigation of urine cultures and received antibiotic
      therapy accordingly. When analyzing all patients in the study, the likelihood of
      adequate clinical response was not significantly different between those who
      received antibiotic therapy based on limited (28/33 = 85%) vs full (18/19 = 95%)
      microbiological investigation of urine cultures (P = 0.40). An average of 183 US
      dollars could be saved per patient by managing symptomatic polymicrobial UTI
      based on a limited vs a full microbiological investigation. These results suggest
      that in adult SCI patients with symptomatic polymicrobial UTI antibiotic therapy
      guided by a limited microbiological investigation may be practical, adequate and
      cost-saving.

PMID- 9267921
TI  - Effects of respiratory muscle training and electrical stimulation of abdominal
      muscles on respiratory capabilities in tetraplegic patients.
AB  - Thirteen tetraplegic patients were included in the study of the effects of
      respiratory muscle training and of electrical stimulation of the abdominal
      muscles on their respiratory capabilities. Each patient was subjected for three 1
      month lasting periods of the study: for inspiratory muscle training, expiratory
      muscle training and for a period without training. The sequence of these three
      periods was random for each patient. Respiratory tests (RT) measuring forced
      vital capacity (FVC) and forced expiratory volume in one second (FEV1) were
      conducted before and following each monthly period. Measurements were taken under
      four sets of conditions: the patients' unassisted efforts, their efforts combined
      with pressure manually applied by a therapist to the upper part of their abdomen,
      and their efforts accompanied by electrical stimulation (ES) of the abdominal
      muscles during the early phase of expirium, once triggered by the therapist and
      once by the patients themselves. RT values were increasing following respiratory
      muscle training and inspiratory training apparently had a slightly greater effect
      than its expiratory counterpart. The increments of values of RT were
      statistically significant (P < 0.05) after the inspiratory muscle training. RT
      measurements were greater when the patient's voluntary effort was combined with
      ES of abdominal muscles than when it was not. This study concludes that
      respiratory muscle training is a potentially effective approach and that ES of
      the abdominal muscles has potentials to improve coughing in tetraplegic patients.

PMID- 9267922
TI  - Gracilis urethromyoplasty--an autologous urinary sphincter for neurologically
      impaired patients with stress incontinence.
AB  - PURPOSE: To investigate the effect of a neurovascularly intact gracilis muscle
      urethral wrap, to be used to restore urinary continence as a transposed urinary
      sphincter graft, in patients with neurogenic lower urinary tract dysfunction.
      METHODS: Five neurologically impaired men with a denervated and damaged urinary
      sphincter mechanisms were treated. The etiology of sphincteric insufficiency
      included sphincter denervation in three patients, external sphincterotomy in one,
      and urethral trauma due to a chronic indwelling catheter in one. All patients
      underwent gracilis urethromyoplasty sphincter reconstruction. Two patients also
      underwent concomitant ileocystoplasty and one patient ileocystostomy because of
      poor bladder compliance and a bladder capacity of < 200 ml. RESULTS: The gracilis
      urethromyoplasty functioned as a new autologous sphincter with follow-ups ranging
      from 6-35 months. The surgery was successful in four patients. Three of the four
      patients were managed with intermittent catheterization, and one managed by
      ileocystostomy. The fifth patient continued to require an indwelling urethral
      catheter. CONCLUSION: Gracilis urethromyoplasty achieves compression of the
      urethra using a neurovascularly intact muscle graft. The functional urethral
      closure, obtained from the gracilis muscle wrap, assures dryness, and permits
      intermittent self-catheterization. It also avoids the risks of infection,
      erosion, or malfunction associated with the artificial urinary sphincter. The
      potential exists for electrical stimulation of this muscle graft to allow
      volitional control of the neo-sphincter mechanism, and voluntary voiding.

PMID- 9267923
TI  - A rare neurological presentation due to ossification of the posterior
      longitudinal ligament of the thoracic spine and ankylosing spondylitis: case
      report.
AB  - Ossification of the posterior longitudinal ligament (OPLL) may be associated with
      certain rheumatic conditions including ankylosing spondylitis (AS), diffuse
      idiopathic skeletal hyperostosis (DISH) or spondylosis. More than 95% of all OPLL
      are localized at the cervical spine. Herein, we report a case of OPLL at the
      thoracic spine in an HLA-B27-positive female patient with ankylosing spondylitis.
      The patient was presented to use with spastic paraparesis. The imaging studies
      included plain roentgenograms, tomograms, myelo-CT and magnetic resonance imaging
      (MRI). A continuous rod-like ossification along the posterior aspects of the
      fourth to sixth thoracic vertebrae with spinal cord compression was noted. The
      patient underwent a laminectomy from T4 to T6. At the second year follow-up
      examination, residual upper back soreness and mild left thigh pain were noted.
      However, the patient had resumed a full daily schedule and could walk freely
      without any support.

PMID- 9267924
TI  - Foramen magnum schwannoma with an unusual clinical presentation: case report.
AB  - This case report illustrates a patient with a unilateral localized epidural
      schwannoma at C1-2 level, showing contralateral spinal cord symptoms and signs.
      The clinical presentation was compared with the neuroradiological examinations
      showing an epidural cord tumor at the right C1-C2 level. However, the
      neurological examination revealed contralateral hemiparesis and ipsilateral
      hemihypoalgesia, indicating a contralateral Brown-Sequard syndrome. We presumed
      with this slow growing tumor, contralateral cord involvement may result from
      counter pressure on the spinal cord, which may be generated by cord deviation and
      by frequent neck rotation.

PMID- 9267925
TI  - A molecular biological approach to neuropathy of the urinary bladder/prostate in
      patients with spinal cord injury.

PMID- 9267926
TI  - Hair as the nidus of a bladder stone in a traumatic paraplegic patient.

PMID- 9267927
TI  - Lymphoid apoptosis during sepsis: now that we've found it, what do we do with it?

PMID- 9267928
TI  - Guideline process improves laboratory use and costs.

PMID- 9267929
TI  - Heatstroke: community prevention and prospective immunotherapeutic interventions.

PMID- 9267930
TI  - Data, data everywhere.

PMID- 9267931
TI  - Inotropes and gut mucosal perfusion: a brake on the motor of multiple organ
      failure?

PMID- 9267932
TI  - Effect of hyperglycemia after cortical injury.

PMID- 9267933
TI  - 100% oxygen in the delivery room is just fine, for now.

PMID- 9267934
TI  - Antibiotics: more than just "bug" killers.

PMID- 9267935
TI  - Survival and functional outcome of children following severe traumatic brain
      injury.

PMID- 9267936
TI  - Nitric oxide infusion during controlled mechanical ventilation.

PMID- 9267937
TI  - Hyperventilation in traumatic brain injury: friend or foe?

PMID- 9267938
TI  - Vasopressin pressor hypersensitivity in vasodilatory septic shock.

PMID- 9267939
TI  - Recombinant N-terminal fragment of bactericidal/permeability increasing protein
      (rBPI21) prevents shock-induced microcirculatory alterations in the liver.
AB  - OBJECTIVE: To investigate the effects of the recombinant 21-kilodalton N-terminal
      fragment of recombinant bactericidal and permeability increasing protein (rBPI21)
      on leukocyte adhesion and the hepatic microcirculation after hemorrhagic shock.
      DESIGN: Prospective, randomized, blinded, and placebo-controlled experimental
      study. SETTING: University research laboratory. SUBJECTS: Anesthetized Sprague
      Dawley rats, weighing 220 to 250 g. INTERVENTIONS: Rats were subjected to 60 mins
      of hemorrhagic shock and subsequent resuscitation to sufficiently restore
      systemic circulation. The microcirculation of the liver was investigated by
      intravital fluorescence microscopy 5 hrs after hemorrhagic shock. Four shock
      groups were compared with a sham-control group. Shock groups received either
      rBPI21 (10 mg/kg) or placebo either before or after shock period. MEASUREMENTS
      AND MAIN RESULTS: No differences were observed in hemodynamic, respiratory, or
      metabolic parameters between the shock groups. However, the hepatic
      microcirculation showed severe deterioration 5 hrs after shock, indicated by
      significantly narrowed sinusoids in all shock groups compared with controls (8.5
      +/- 0.3 microm vs. 10.0 +/- 0.4 pm). Leukocyte adhesion was markedly increased to
      comparable values in both placebo groups (619 cells/mm2 and 644 cells/mm2; sham,
      168 cells/mm2). Neutralization of endotoxin by administration of rBPI21 before or
      after shock resulted in plain reduction of pathologic leukocyte-endothelial
      interaction (138 cells/mm2 and 85 cells/mm2). CONCLUSION: The results support the
      hypothesis that endotoxin induces microcirculatory alterations after shock, and
      further suggest a potentially beneficial role of rBPI21 in the treatment of
      posttraumatic endotoxin-induced inflammatory reactions.

PMID- 9267940
TI  - Preventable adverse drug events in hospitalized patients: a comparative study of
      intensive care and general care units.
AB  - OBJECTIVES: To compare the frequency and preventability of adverse drug events
      and potential adverse drug events in intensive care units (ICUs) and non-ICUs. To
      evaluate systems factors involving the individual caregivers, care unit teams,
      and patients involved in each adverse drug event by comparing ICUs with non-ICUs
      and medical ICUs with surgical ICUs. DESIGN: Prospective cohort study.
      Participants included all 4,031 adult admissions to a stratified, random sample
      of 11 medical and surgical units in two tertiary care hospitals over a 6-month
      period. Units included two medical and three surgical ICUs and four medical and
      two surgical general care units. SETTING: Two tertiary care hospitals: Eleven
      medical and surgical units, including two medical and three surgical ICUs.
      PATIENTS: Adult admissions (n = 4,031). INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: Rate of preventable adverse drug events and potential adverse drug
      events, length of stay, charges, costs, and measures of the unit's environment.
      Incidents were detected by stimulated self-report by nurses and pharmacists and
      by daily review of all charts by nurse investigators. Incidents were subsequently
      classified by two independent reviewers as to whether they represented adverse
      drug events or potential adverse drug events and as to severity and
      preventability. Those individuals involved in the preventable adverse drug event
      and potential adverse drug event underwent detailed interviews by peer case
      investigators. The rate of preventable adverse drug events and potential adverse
      drug events in ICUs was 19 events per 1000 patient days, nearly twice that rate
      of non-ICUs (p <.01). The medical ICU rate (25 events per 1000 patient days) was
      significantly (p <.05) higher than the surgical ICU rate (14 events per 1000
      patient days). When adjusted for the number of drugs used in the previous 24 hrs
      or ordered since admission, there were no differences in rates between ICUs and
      non-ICUs. ICU acuity, length of stay, and severity of the adverse drug event were
      greater in ICUs than non-ICUs, but there were no differences between medical ICU
      and surgical ICU patients. Structured interviews indicated almost no differences
      between ICUs and non-ICUs for many characteristics of the patient, patient care
      team, systems, and individual caregivers. CONCLUSIONS: The rate of preventable
      and potential adverse drug events was twice as high in ICUs compared with non
      ICUs. However, when adjusted for the number of drugs ordered, there was no
      greater likelihood for preventable adverse drug events and potential adverse drug
      events to occur in ICUs than in non-ICUs. Preventable adverse drug events and
      potential adverse drug events occurred in units that functioned normally and
      involved caregivers who were working under reasonably normal circumstances, not
      at the extremes of workload, stress, or a difficult environment.

PMID- 9267941
TI  - Apoptosis in lymphoid and parenchymal cells during sepsis: findings in normal and
      T- and B-cell-deficient mice.
AB  - OBJECTIVES: To determine if apoptosis (programmed cell death) occurs systemically
      in lymphoid and parenchymal cells during sepsis. To examine the potential role of
      T and B cells in the apoptotic process using knockout mice deficient in mature T
      and B lymphocytes. DESIGN: Prospective, randomized, controlled trial. SETTING:
      Animal laboratory in a university medical setting. INTERVENTIONS: Cecal ligation
      and puncture (CLP) (n = 34) or sham surgery (n = 13) was performed in female ND4
      mice and, 15 to 22 hrs postoperatively, thymus, lung, heart, spleen, ileum,
      colon, liver, kidney, brain, and muscle were obtained and examined for apoptosis.
      A second group of mice (Rag-1) which are totally deficient in mature T and B
      cells also underwent CLP (n = 14) or sham surgery (n = 14) and had examination of
      tissues for apoptosis. MEASUREMENTS AND MAIN RESULTS: Four methods with varying
      sensitivities and specificities were used to detect apoptosis, including: a) DNA
      agarose gel electrophoresis; b) terminal deoxynucleotidyl transferase mediated
      dUTP nick end labeling (TUNEL); c) electron microscopy; and d) light microscopy.
      In CLP mice, multiple methods demonstrated apoptosis in lymphocytes in thymus,
      spleen, ileum, colon, lung, and skeletal muscle. In addition to lymphocytes,
      parenchymal cells in ileum, colon, lung, and to a lesser extent, in skeletal
      muscle and kidney were apoptotic in CLP mice. There was no evidence of apoptosis
      by any method of detection in liver, brain, or heart. Results in Rag-1 mice which
      are deficient in T and B cells demonstrated extensive apoptosis in thymus,
      spleen, and ileum with less degrees of apoptosis in colon and lung. Both lymphoid
      cells and parenchymal cells were apoptotic. Rag-1 mice which underwent CLP did
      not die prematurely and there were no apparent observable differences in the
      physical response (tachypnea, piloerection, lethargy, etc), or intra-abdominal
      bowel inflammation/adhesions compared with CLP mice with normal T and B cells.
      CONCLUSIONS: Apoptosis is an important mechanism of cell death in lymphocytes and
      parenchymal cells in sepsis and occurs systemically in many organs. Apoptosis may
      be an important cause of immunologic suppression in sepsis by inducing widespread
      lymphocyte depletion. Alternately, apoptosis may be beneficial to host survival
      by down-regulating the inflammatory response which accompanies sepsis. The degree
      to which parenchymal cell apoptosis is contributing to multiple organ failure
      cannot be determined from the present study. Findings in Rag-1 mice demonstrate
      that mature T and B cells and their secretory products are not necessary for
      apoptosis to occur during sepsis and that apoptotic cell death is not restricted
      to T or B cells. Apoptosis may be a key regulator of the balance between the pro-
      and anti-inflammatory process.

PMID- 9267942
TI  - Practice guideline for arterial blood gas measurement in the intensive care unit
      decreases numbers and increases appropriateness of tests.
AB  - OBJECTIVE: To test the hypothesis that implementation of a practice guideline for
      blood gas measurement would decrease numbers and increase appropriateness of
      tests (according to criteria in the guideline) for up to 1 yr after introduction
      of the guideline. DESIGN: Numbers of tests and appropriateness of each test were
      measured retrospectively during each of five periods: two baseline periods 2 yrs
      and 1 yr before introduction of the guideline and three follow-up periods 2 to 3
      months, 6 to 7 months, and 12 to 13 months after introduction of the guideline.
      SETTING: A ten-bed multidisciplinary intensive care unit (ICU) within a 500-bed
      tertiary teaching hospital. PATIENTS: A random sample of 30 patients admitted to
      the ICU during each of the periods specified above. INTERVENTIONS: The nominal
      group process was used to develop a new guideline and a multipronged educational
      approach was used to facilitate implementation of the guideline. MEASUREMENTS AND
      MAIN RESULTS: At 2 to 3 months, test numbers decreased from 4.9 +/- 1.6 to 3.1 +/
      1.8 (SD) tests/patient/day and to 2.4 +/- 1.2 tests/patient/day at 12 to 13
      months. Appropriateness increased from a mean of 44% at baseline to 78% at 2 to 3
      months and 79% at 12 to 13 months. There were no differences in Acute Physiology
      and Chronic Health Evaluation scores or ICU mortality among the patient groups
      and no differences in number of ventilator days or time to wean from ventilation.
      Cost-minimization analysis showed that the incremental cost-saving 1 yr after
      introduction of the guideline was $19.18 per patient per day. CONCLUSIONS:
      Implementation of this guideline for arterial blood gas measurement increases
      efficiency of test utilization without prolonging mechanical ventilation or
      affecting outcome.

PMID- 9267943
TI  - Concentrations of soluble tumor necrosis factor and interleukin-6 receptors in
      heatstroke and heatstress.
AB  - OBJECTIVE: Increased proinflammatory cytokine concentrations have been implicated
      in the pathogenesis of heatstroke. Soluble cytokine receptors can modulate
      circulating cytokine activities. We examined the possible role of soluble tumor
      necrosis factor receptors (sTNFR 60, sTNFR 80) and interleukin-6 receptor (sIL
      6R) in heatstroke by determining their concentrations before and after cooling,
      as well as in heatstressed controls. DESIGN: Prospective controlled study.
      SETTING: Heatstroke Center, Makkah, Saudi Arabia (1993 pilgrimage). PATIENTS:
      Twenty-five consecutive heatstroke patients before and after cooling, 14
      heatstressed controls (HSC), and 13 normal controls (NC). MEASUREMENTS AND MAIN
      RESULTS: Concentrations of sTNFR 60, sTNFR 80, and sIL-6R, as well as their
      ligands, were measured using commercially available enzyme-linked immunosorbent
      assay kits. Mean sTNFR 60 concentration was increased in heatstroke (p <.0001,
      vs. NC; p < .0001, vs. HSC) and in HSC (p = .004, vs. NC). Mean sTNFR 80
      concentration was increased in heatstroke and decreased in HSC (p = .01,
      heatstroke vs. HSC). Mean sIL-6R concentration was decreased in heatstroke and
      increased in HSC (p = .04, heatstroke vs. NC; p = .001, heatstroke vs. HSC). IL-6
      was undetectable in NC and mean IL-6 concentration was more increased in
      heatstroke than in HSC (p = .001). Rectal temperature and creatinine
      concentrations correlated significantly with sTNFR 60, sTNFR 80, sIL-6R, and IL-6
      concentrations. After cooling, mean concentrations of sIL-6R and sTNFR 80
      increased significantly, whereas the mean sTNFR 60 concentration did not change.
      Residual neurologic deficits were associated with higher precooling IL-6 (p =
      .002) and postcooling sTNFRs (p < .0001) concentrations. CONCLUSIONS: Significant
      changes in cytokine receptor concentrations are associated with heatstress. In
      heatstroke, the changes are more pronounced, and for some cytokine receptors, the
      changes are in the opposite direction (compared with changes in heatstress).
      Concentrations of IL-6 and sTNFRs correlate with hyperthermia and outcome.
      Cooling did not normalize sTNFR concentrations, suggesting failure to control the
      inflammatory response.

PMID- 9267944
TI  - Can hospital discharge diagnoses be used for intensive care unit administrative
      and quality management functions?
AB  - OBJECTIVE: To determine whether hospital discharge diagnoses can be used for
      intensive care unit (ICU)-related activities. DESIGN: Comparison between the
      diagnoses coded by physicians at the time of ICU admission and those diagnoses
      coded by medical records personnel. SETTING: University hospital adult surgical
      ICU. PATIENTS: Consecutive ICU admissions (n = 622). INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: The ICU admission and hospital discharge codes
      were compared in two ways. Initially, each discharge code was subtracted from the
      corresponding ICU admission code. There was no difference in 150 (24%) cases. In
      216 (35%) patients, the codes differed by +/-10. In 221 (36%) instances, the
      codes differed by >200. The secondary discharge diagnoses were also compared with
      the ICU admission diagnoses. In 56 patients, the ICU admission diagnosis was one
      of the secondary diagnoses. The second comparison involved having two physicians
      not associated with the study examine each pair of codes to determine if the two
      diagnoses were medically different. Review of the codes by physicians not
      involved in the study found that in 318 (48%) patients, the two diagnoses were
      not different, i.e., the codes were either the same or the codes were so similar
      as not to functionally change the actual diagnosis. CONCLUSIONS: The primary
      discharge diagnosis often failed to reflect the reason for ICU admission, making
      it impossible to consistently establish the reason for ICU admission from the
      discharge data. The reason for ICU admission was also frequently not included
      among the secondary discharge diagnoses. Administrative data are therefore not
      useful for ICU quality management and other functions. Intensivists need to
      establish their own databases.

PMID- 9267945
TI  - A retrospective review of a large cohort of patients undergoing the process of
      withholding or withdrawal of life support.
AB  - OBJECTIVES: To determine the proportion of patients who died as a result of the
      withdrawal or withholding of life support (WD/WHLS) in the intensive care units
      (ICUs) of three teaching hospitals and to describe the process involved by
      determining: a) why the decision was made to withdraw support (WDLS); b) when
      WDLS took place; and c) how the WDLS process was conducted. DESIGN: Retrospective
      cohort study. SETTING: Three university-affiliated ICUs. PATIENTS: Four hundred
      nineteen patients who died in one of three academic, tertiary care ICUs over a 1
      yr period. INTERVENTIONS: Retrospective chart review. Data collected included
      age, gender, admitting diagnoses, comorbid disease, Acute Physiology and Chronic
      Health Evaluation II score, and mode of death (brain death, death due to
      withholding of life support, death due to WDLS, or death despite ongoing
      therapy). For those patients dying due to WDLS, the reason for WDLS, person
      initiating discussion, timing of WDLS, degree of organ dysfunction, order of
      withdrawal of life support modalities, and the use of sedatives and analgesics
      were recorded. MEASUREMENTS AND MAIN RESULTS: Seventy percent of patients died by
      WD/WHLS and 8.4% were brain dead. Patients undergoing WD/WHLS were older and had
      a longer length of stay than patients dying from other causes. Poor prognosis was
      the most common reason given for WDLS, reflected by significant organ dysfunction
      at the time of WDLS. Future quality of life was a less frequently cited reason.
      Most patients undergoing WDLS did so early in their ICU stay, although time to
      WDLS appeared to reflect diagnostic group. Few meetings occurred before WDLS and
      death occurred soon after initiating WDLS. There was a preference of withdrawing
      mechanical ventilation last and large amounts of morphine (mean 21 +/- 33 [SD]
      mg/hr) and benzodiazepines (mean 8.6 +/- 11 mg/hr) were used. Little variability
      in practice was apparent among the studied ICUs. CONCLUSIONS: Similar to other
      studies, WD/WHLS was the most common cause of death in academic ICUs and poor
      patient prognosis was considered the most important factor in deciding on WDLS.
      However, in contrast to other studies, future quality of life was not as
      frequently cited a reason for WDLS and larger amounts of morphine were used
      during WDLS. These discrepancies suggest areas for potential future research.

PMID- 9267946
TI  - Metabolic and calorigenic effects of dopexamine in healthy volunteers.
AB  - OBJECTIVE: To evaluate metabolic and calorigenic effects of dopexamine in healthy
      volunteers. DESIGN: Prospective, randomized trial. SETTING: Laboratory of the
      University Department of Anesthesiology. SUBJECTS: Eight volunteers.
      INTERVENTIONS: After a control period, dopexamine was administered using four
      infusion rates (0.75, 1.5, 3.0, and 6.0 microg/kg/min). MEASUREMENTS AND MAIN
      RESULTS: Blood pressure, heart rate, oxygen consumption (VO2), and the plasma
      concentration of potassium, glucose, lactate, and norepinephrine were measured.
      Typical hemodynamic responses were seen. VO2 increased from 122 +/- 11 (SD) to
      150 +/- 9 mL/min/m2 during the highest dopexamine infusion rate. Plasma potassium
      concentration decreased only during the highest infusion rate. Plasma glucose
      concentration increased during infusion rates of 3 and 6 microg/kg/min of
      dopexamine, from 90 +/- 5 to 99 +/- 5 mg/dL (5.0 +/- 0.3 to 5.5 +/- 0.3 mmol/L),
      and from 87 +/- 7 to 103 +/- 11 mg/dL (4.8 +/- 0.4 to 5.7 +/- 0.6 mmol/L),
      respectively. Lactate did not increase during dopexamine infusion. Plasma
      norepinephrine concentration increased during all four infusion rates.
      CONCLUSION: It was not possible to differentiate the adrenergic receptor subtype
      responsible for the calorigenic and metabolic effects, since the putative beta2
      adrenergic-receptor agonist, dopexamine, caused an increase in the plasma
      concentration of the beta1 adrenergic-receptor agonist, norepinephrine. Since
      beta2 adrenergic receptor-mediated effects such as hypokalemia were found only at
      infusion rates > or = 3 microg/kg/min, the effects of dopexamine at infusion
      rates < 3 microg/kg/min may be mainly mediated by stimulation of dopaminergic
      receptors and the indirect sympathomimetic action.

PMID- 9267947
TI  - Relationship between leukocyte count and patient risk for excessive blood loss
      after cardiac surgery.
AB  - OBJECTIVE: To evaluate the relationship between leukocyte counts and risk for
      excessive blood loss after cardiac surgery when including numerous demographic,
      operative, and laboratory factors in the comparison. DESIGN: A prospective,
      clinical evaluation. SETTING: A point-of-care laboratory and the cardiac surgical
      unit of a university-affiliated tertiary center. PATIENTS: Patient-related and
      hematologic variables were measured, using blood specimens obtained from 89
      hospitalized patients who underwent cardiac surgery involving cardiopulmonary
      bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic,
      operative, and transfusion-related data were recorded for each patient. Routinely
      obtained measurements of laboratory-based prothrombin time, partial
      thromboplastin time, complete blood count, and bleeding time were recorded.
      Hemoglobin concentration, platelet count, and red and white blood cell counts
      were measured with an on-site instrument before initiation (pre-cardiopulmonary
      bypass) and before discontinuation (end-cardiopulmonary bypass) of
      cardiopulmonary bypass. Hematocrit was calculated using recorded variables, and
      white blood cell percent change values were calculated using white blood cell
      counts from both periods, using the following formula: [(end-cardiopulmonary
      bypass - pre-cardiopulmonary bypass)/pre-cardiopulmonary bypass] x 100. When we
      excluded four patients who had a surgical source of post-cardiopulmonary bypass
      bleeding, significant (p < .0001) relationships were observed between white blood
      cell count (r2 = .46) and white blood cell percent change values (r2 = .71) and
      cumulative mediastinal chest tube drainage in the first 4 postoperative hours in
      85 patients. Bayes theorem was used to evaluate the predictive ability of
      hematologic measurements in identifying patients with excessive bleeding (n =
      24), defined as >1000 mL of cumulative chest tube drainage in the first 24
      postoperative hours, when compared with patients without excessive bleeding (n =
      61). Demographic and operative variables were similar between these patients
      except that patients with excessive bleeding required more red blood cell,
      platelet, and plasma transfusions during the postoperative interval.
      Significantly (p < .0001) greater white blood cell percent change values were
      obtained in the excessive bleeding cohort (119 +/- 93 percent change) when
      compared with patients without excessive bleeding (28 +/- 36 percent change).
      CONCLUSIONS: On-site measurements of white blood cell count, as an index of the
      inflammatory response to extracorporeal circulation, may be useful in identifying
      patients at increased risk for excessive bleeding. Further studies are needed to
      examine whether white blood cell counts during multiple cardiopulmonary bypass
      periods may identify patients with an exaggerated inflammatory response to
      extracorporeal circulation. By using this information, physicians may be able to
      intervene with anti-inflammatory medications and blood preservation techniques.

PMID- 9267948
TI  - Insights into the increased oxygen demand during chest physiotherapy.
AB  - OBJECTIVES: To determine the mechanism responsible for the increase in oxygen
      consumption (VO2) during chest physical therapy. Specifically, to examine the
      hypothesis that muscular activity is the major contributor to the increase in
      oxygen demand. DESIGN: Prospective, observational study. SETTING: University
      hospital surgical intensive care unit. PATIENTS: Phase one included 13 patients
      who were mechanically ventilated after coronary artery bypass surgery. Phase two
      involved seven mechanically ventilated patients who had undergone major vascular
      or abdominal surgery. INTERVENTIONS: Phase one involved turning patients to the
      lateral decubitus position. During the second phase, patients were given
      midazolam (0.15 microg/kg) 2 mins before an initial chest physiotherapy session
      and midazolam plus vecuronium (0.7 mg/kg) before a subsequent session.
      Physiologic measurements were made during the resting periods before and
      following each session, as well as at the completion of the intervention.
      MEASUREMENTS AND MAIN RESULTS: Turning patients to the lateral position resulted
      in significant increases in oxygen uptake and CO2 elimination (VCO2). VO2
      increased from 219 +/- 21 (SD) mL/min at rest to 324 +/- 58 mL/min (p <.05) with
      turning. These increases in oxygen demand were met by increases in both oxygen
      delivery (852 +/- 238 mL/min at rest to 1116 +/- 430 mL/min, p < .05) and
      extraction (0.27 +/- 0.7 at rest to 0.32 +/- 0.09, p < .05). There were
      associated increases in hemodynamic and respiratory variables including heart
      rate and systolic blood pressure. The administration of vecuronium completely
      suppressed the 50% increases in VO2 and VCO2 seen without the use of a muscle
      relaxant. The increases in systolic blood pressure were unaffected by vecuronium.
      The magnitude of the increase in PaCO2 (32 +/- 5 torr [4.3 +/- 0.7 kPa] at rest
      to 36 +/- 5 torr [4.8 +/- 0.7 kPa] during therapy, p < .05), was not accentuated
      by vecuronium (30 +/- 4 torr [4.0 +/- 0.5 kPa] to 35 +/- 6 torr [4.7 +/- 0.8
      kPa], p < .05) despite a lack of any increase in minute ventilation or
      respiratory rate. This change was due to the parallel suppression of VCO2.
      CONCLUSIONS: The increase in metabolic demand during chest physiotherapy is the
      result of increased muscular activity as evidenced by the suppression of VO2
      following the administration of the muscle relaxant and the observation that
      turning a patient into the lateral decubitus position produces similar increases
      in VO2. The increases in blood pressure and cardiac output are due to another
      mechanism, most likely enhanced sympathetic output. The increase in physiologic
      activity produced by chest physiotherapy is thus secondary to both exercise-like
      and stress-like responses.

PMID- 9267949
TI  - Administration of human recombinant insulin-like growth factor-I in critically
      ill patients.
AB  - OBJECTIVES: To study the pharmacokinetics of a single subcutaneous dose of
      recombinant human insulin-like growth factor-I (IGF-I) in patients with systemic
      inflammatory response syndrome in the intensive care unit (ICU). To evaluate the
      effects of exogenous recombinant human IGF-I on circulating concentrations of IGF
      I binding protein-1 (IGFBP-1), IGF-I binding protein-3 (IGFBP-3), and growth
      hormone in the critically ill patient; to assess the safety of the subcutaneous
      administration of 40 microg/kg of recombinant human IGF-I in these patients; and
      to investigate any effect this dose might have on nitrogen balance, creatinine
      clearance, and serum electrolyte and lipid concentrations. DESIGN: Open-labeled,
      noncontrolled, prospective, single-dose study of eight fully evaluable ICU
      patients with systemic inflammatory response syndrome. SETTING: ICUs in a
      teaching hospital and a linked district general hospital in England. PATIENTS:
      Nine patients were examined, eight of whom were fully evaluable. INTERVENTIONS:
      Subcutaneous administration of 40 microg/kg of recombinant human IGF-I.
      MEASUREMENTS AND MAIN RESULTS: Blood samples were taken 24 hrs before the
      subcutaneous injection of 40 microg/kg of recombinant human IGF-I, and for 48 hrs
      thereafter. Urine was collected throughout this period. Serum concentrations of
      IGF-I, IGFBP-1, IGFBP-3, growth hormone, and insulin were measured by
      radioimmunoassay. IGF-I concentrations (median and range) increased significantly
      above baseline values (35 ng/mL [20 to 144]) from 15 mins (p < .02) until 10 hrs
      (p < .02) after injection of recombinant human IGF-I. Peak IGF-I concentrations
      were sustained from 2 hrs (90.5 ng/mL [23 to 228]) to 5 hrs (88.5 ng/mL [29 to
      300]). By 24 hrs, circulating IGF-I concentrations had returned to baseline
      values. Baseline IGF-I concentrations were extremely low, and although peak
      values were three times greater, these values only approached the fifth
      percentile of defined reference ranges for normal values. Compared with values in
      less seriously ill patients, maximum IGF-I concentrations were reached earlier,
      the elimination half-life was shorter, clearance was more rapid, and the apparent
      volume of distribution was similar. IGFBP-3 concentrations also increased after
      recombinant human IGF-I injection, and at 3 to 4 hrs were significantly elevated,
      from 30 mins (p = .04) to 8 hrs (p = .04). There was marked between-patient
      variability in changes in circulating IGF-I, and IGFBP-1, and IGFBP-3
      concentrations. More severely ill patients had the lowest circulating IGF-I
      concentrations and the least response to exogenous recombinant human IGF-I.
      Elevated baseline circulating growth hormone concentrations (2.3 ng/mL, range 0.8
      to 4 [5.1 mU/L, 1.5 to 8]) were significantly depressed from 4 hrs (0.5 ng/mL,
      0.5 to 1.5 [1 mU/L, 1 to 3], p = .01) to 6 hrs (0.8 ng/mL, 0.5 to 4 [1.5 mU/L, 1
      to 8], p = .02) after recombinant human IGF-I administration. CONCLUSION: We
      observed no adverse effects (e.g., hypoglycemia) that could be attributed to
      recombinant human IGF-I therapy.

PMID- 9267950
TI  - Effect of classic heatstroke on serum procalcitonin.
AB  - OBJECTIVE: Procalcitonin, the precursor peptide of calcitonin, has been shown to
      be a serum marker of the severity and mortality of several systemic inflammatory
      response syndromes. This study addressed the correlation of serum procalcitonin
      with the course of classic (nonexertional) heatstroke. DESIGN: Serum samples were
      collected prospectively every 6 hrs for 24 hrs. SETTING: Heatstroke treatment
      unit, Makkah, Saudi Arabia. PATIENTS: A total of 25 patients were admitted during
      the annual Hajj pilgrimage in 1994. Ten patients evaluated in the same treatment
      center with minor illnesses and without pyrexia served as controls.
      INTERVENTIONS: Patients were cooled according to an established evaporation
      method. MEASUREMENTS AND MAIN RESULTS: Standard critical care parameters
      including continuous rectal temperature. A rapid immunochemical assay for serum
      procalcitonin was utilized. The mean serum procalcitonin was elevated 20-fold on
      admission in patients with heatstroke compared with controls (p < .011). The
      procalcitonin concentration subsequently increased to a plateau by 6 hrs and
      remained increased at 24 hrs, compared with the admission level (p < .0001). In
      this study, 77% of the patients with heatstroke survived. A subgroup analysis
      demonstrated that the patients who survived had a significantly higher
      procalcitonin concentration than those patients who died of heatstroke; a
      procalcitonin concentration of >0.5 ng/mL (>0.15 nmol/L) at 6 hrs predicted
      survival (p = .02). CONCLUSION: Classic heatstroke is associated with increased
      concentrations of serum procalcitonin, particularly among survivors. Further
      studies are required to elucidate the source and action(s) of procalcitonin as
      well as its relationship to cytokine activation.

PMID- 9267951
TI  - Reduced serum Gc-globulin concentrations in patients with fulminant hepatic
      failure: association with multiple organ failure.
AB  - OBJECTIVE: To evaluate the association between admission serum concentrations of
      the actin-scavenger, Gc-globulin, and the subsequent development of multiple
      organ failure in patients with fulminant hepatic failure. DESIGN: Retrospective
      study. SETTING: A hepatologic intensive care unit. PATIENTS: Seventy-nine
      patients with hepatic encephalopathy grade 3 or 4. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Serum admission concentrations of both total and
      nonactin-complexed (free) Gc-globulin were determined. The development of
      cardiovascular failure, renal failure, pulmonary failure, intracranial
      hypertension, and infections were recorded in each patient. Both total and free
      Gc-globulin values were significantly lower in the patients, compared with normal
      controls. The Gc-globulin values were significantly reduced in patients who
      subsequently developed cardiovascular failure (p < .01), intracranial
      hypertension (p < .001), and infections (p < .001), compared with those patients
      who did not. No differences were found between patients with and without
      pulmonary or renal failure. Patients with total Gc-globulin values in the lowest
      quintile had on average 2.6 organ failures, whereas patients with Gc-globulin
      concentrations in the highest quintile had 0.9 organ failures. The corresponding
      figures for the lowest and highest quintiles of free Gc-globulin were 3.0 and 1.1
      organ failures, respectively. Both total and free Gc-globulin were inversely
      correlated to the number of organ failures (p < .005 in both cases). Patients
      with multiple organ failure (> or = 2 organ failures) had significantly reduced
      Gc-globulin values compared with patients without multiple organ failure (p <
      .0001). CONCLUSIONS: In patients with fulminant hepatic failure, the lowest
      admission Gc-globulin concentrations were associated with the subsequent
      development of cardiovascular failure, intracranial hypertension, and infections.
      Lack of Gc-globulin correlated significantly with the development of multiple
      organ failure and may be pathogenetically involved in this condition.

PMID- 9267952
TI  - Dobutamine improves gastrointestinal mucosal blood flow in a porcine model of
      endotoxic shock.
AB  - OBJECTIVE: To test the hypothesis that saline solution plus dobutamine increases
      gastrointestinal mucosal perfusion better than saline solution alone in a model
      of endotoxic shock. DESIGN: Prospective, randomized, unblinded study. SETTING:
      Animal research laboratory affiliated with a university teaching hospital.
      SUBJECTS: Twelve female pigs, weighing 30 to 32 kg. INTERVENTIONS: Animals were
      anesthetized, and their lungs were mechanically ventilated. Catheters were
      inserted into the right atrium, pulmonary artery, and carotid artery for blood
      sampling and blood pressure and cardiac output measurements. A tonometer and a
      laser Doppler probe were placed in the lumen of the stomach and the ileum for
      determination of mucosal acid-base status and measurement of mucosal blood flow.
      Group 1 animals (n = 6) received an infusion (T = 0 min) of 150 mcirog/kg
      Escherichia coli endotoxin and normal saline solution (0.3 mL/kg/min). Group 2
      animals (n = 6) received an infusion of endotoxin and were resuscitated with the
      same method as used in group 1, but an infusion of dobutamine (5 microg/kg/min)
      was begun at T = 60 mins, and continued for the duration of the experiment.
      MEASUREMENTS AND MAIN RESULTS: Both experimental regimens produced shock, with
      decreased mean arterial pressure and systemic vascular resistance, without change
      in cardiac output and oxygen delivery. Endotoxin plus saline infusion decreased
      gastrointestinal mucosal blood flow to <60% of baseline and decreased
      gastrointestinal pH. In contrast, gastrointestinal mucosal blood flow returned to
      baseline values, and intramucosal pH tended to normalize by the end of the saline
      solution plus dobutamine resuscitative protocol. CONCLUSION: Compared with saline
      solution alone, saline solution plus dobutamine increased blood flow to the
      gastrointestinal mucosa, and may have partially improved oxygenation.

PMID- 9267953
TI  - Hyperglycemia increases brain injury caused by secondary ischemia after cortical
      impact injury in rats.
AB  - OBJECTIVE: To examine the effects of glucose infusion on the histologic brain
      damage caused by controlled cortical impact injury alone and by cortical impact
      injury complicated by secondary ischemia. DESIGN: Prospective, randomized study.
      SETTING: University laboratory. SUBJECTS: Male Long-Evans rats. INTERVENTIONS:
      Three experimental conditions were studied: a) 2.5-mm deformation impact
      (velocity 4 m/sec) injury followed by 40 mins of bilateral carotid occlusion; b)
      sham impact injury followed by 40 mins of bilateral carotid occlusion; and c) 2.5
      mm deformation impact (velocity 4 m/sec) injury followed by sham carotid
      occlusion. For each experimental condition, animals were randomized to receive
      either glucose solution or saline solution before the induced injury and the sham
      impact injury. Contusion volume and neuron density in the CA1 and CA3 regions of
      the hippocampus were measured 2 wks after the injury. MEASUREMENTS AND MAIN
      RESULTS: Parenteral administration of 2.2 g/kg glucose solution increased the
      blood glucose concentration from 6.7 +/- 3.3 to 17.9 +/- 10.6 mmol/L before the
      impact injury, and to 12.3 +/- 5.6 mmol/L before carotid occlusion. Hyperglycemia
      had the greatest effect on the consequences of the impact injury complicated by
      secondary ischemia, increasing contusion volume from 1 to 30.6 mm3 in the animals
      that received saline or glucose solution, respectively (p = .005), and reducing
      the density of normal appearing neurons in the CA1 area of the hippocampus from
      201 to 144 cells/mm2 in the animals that received saline solution and glucose
      solution, respectively (p = .038). The impact injury alone and bilateral carotid
      occlusion alone caused minimal neuronal loss in the hippocampus and minimal
      contusion or infarction at the impact site. Individually, these mild injuries
      were not adversely affected by infusion of glucose solution. CONCLUSION:
      Hyperglycemia increases brain damage when traumatic brain injury is complicated
      by secondary ischemia.

PMID- 9267954
TI  - Effects of hypoxemia and reoxygenation with 21% or 100% oxygen in newborn
      piglets: extracellular hypoxanthine in cerebral cortex and femoral muscle.
AB  - OBJECTIVE: To determine whether reoxygenation with an FIO2 of 0.21 (21% oxygen)
      is preferable to an FIO2 of 1.0 (100% oxygen) in normalizing brain and muscle
      hypoxia in the newborn. DESIGN: Prospective, randomized, animal study. SETTING:
      Hospital surgical research laboratory. SUBJECTS: Twenty-six anesthetized,
      mechanically ventilated, domestic piglets, 2 to 5 days of age. INTERVENTIONS: The
      piglets were randomized to control or hypoxemia groups. Hypoxemia was induced by
      ventilating the piglets with 8% oxygen in nitrogen, which was continued until
      mean arterial pressure decreased to <20 mm Hg. After hypoxemia, the piglets were
      further randomized to receive reoxygenation with an FIO2 of 0.21 (21% oxygen
      group, n = 9) or an FIO2 of 1.0 for 30 mins followed by an FIO2 of 0.21 (100%
      oxygen group, n = 9), and followed for 5 hrs. The piglets in the control group
      were mechanically ventilated with 21% oxygen (n = 8). MEASUREMENTS AND MAIN
      RESULTS: We measured extracellular concentrations of hypoxanthine in the cerebral
      cortex and femoral muscle (in vivo microdialysis), plasma hypoxanthine
      concentrations, cerebral arterial-venous differences for hypoxanthine, acid base
      balances, arterial and venous (sagittal sinus) blood gases, and mean arterial
      pressures. The lowest pH values of 6.91 +/- 0.11 (21% oxygen group, mean +/- SD)
      and 6.90 +/- 0.07 (100% oxygen group) were reached at the end of hypoxemia and
      then normalized during the reoxygenation period. Plasma hypoxanthine increased
      during hypoxemia from 28.1 +/- 9.3 to 119.1 +/- 31.9 micromol/L in the 21% oxygen
      group (p < .001) and from 32.6 +/0- 14.5 to 135.0 +/- 31.4 micromol/L in the 100%
      oxygen group (p <.001). Plasma hypoxanthine concentrations then normalized over
      the next 2 hrs in both groups. In the cerebral cortex, extracellular
      concentrations of hypoxanthine increased during hypoxemia from 3.9 +/- 2.8 to
      20.2 +/- 7.4 micromol/L in the 21% oxygen group (p < .001) and from 5.9 +/- 5.0
      to 25.1 +/- 7.1 micromol/L in the 100% oxygen group (p < .001). In contrast to
      plasma hypoxanthine, extracellular hypoxanthine in the cerebral cortex increased
      significantly further during early reoxygenation, and, within the first 30 mins,
      reached maximum values of 24.9 +/- 6.3 micromol/L in the 21% oxygen group (p <
      .01) and 34.8 +/- 10.9 micromol/L in the 100% oxygen group (p < .001). This
      increase was significantly larger in the 100% oxygen group than in the 21% oxygen
      group (9.7 +/- 4.7 vs. 4.7 +/- 2.6 micromol/L, p < .05). There were no
      significant differences between the two reoxygenated groups in duration of
      hypoxemia, hypoxanthine concentrations in femoral muscle, plasma hypoxanthine
      concentrations, pH, or mean arterial pressure. The cerebral arterial-venous
      difference for hypoxanthine was positive both at baseline, at the end of
      hypoxemia, and after 30 mins and 300 mins of reoxygenation, and no differences
      were found between the two reoxygenated groups. CONCLUSIONS: Significantly higher
      extracellular concentrations of hypoxanthine were found in the cerebral cortex
      during the initial period of reoxygenation with 100% oxygen compared with 21%
      oxygen. Hypoxanthine is a marker of hypoxia, and reflects the intracellular
      energy status. These results therefore suggest a possibly more severe impairment
      of energy metabolism in the cerebral cortex or an increased blood-brain barrier
      damage during reoxygenation with 100% oxygen compared with 21% oxygen in this
      newborn piglet hypoxia model.

PMID- 9267955
TI  - Effect of ciprofloxacin on the accumulation of interleukin-6, interleukin-8, and
      nitrite from a human endothelial cell model of sepsis.
AB  - OBJECTIVE: To determine the effect of the quinolone antibiotic ciprofloxacin, on
      interleukin-6, interleukin-8, and nitrite production by human endothelial cells.
      DESIGN: Controlled cell culture experiments examining the immunomodulatory
      effects of an antibiotic. SETTING: University research laboratory attached to a
      large teaching hospital. SUBJECTS: A human endothelial cell line. MEASUREMENTS
      AND MAIN RESULTS: Cells were incubated with tumor necrosis factor-alpha and
      interleukin-1beta in the presence of a range of ciprofloxacin concentrations.
      Interleukin-6, interleukin-8, and nitrite concentrations were measured in culture
      supernatants after 24 hrs using enzyme immunoassay. Ciprofloxacin decreased
      interleukin-6 accumulation (p = .001). Interleukin-8 was decreased at lower
      ciprofloxacin concentrations (p = .017) but was increased at 100 microg/mL (p =
      .0039). Ciprofloxacin had no effect on nitrite accumulation (p = .38).
      CONCLUSIONS: Ciprofloxacin differentially modulates interleukin-6 and interleukin
      8 expression. The response to infection is coordinated by a cascade of cytokines
      and other mediators. The widespread use of ciprofloxacin in patients with severe
      infections is likely to result in alterations in local concentrations of
      cytokines. Selective control of cytokine concentrations by antibacterial agents
      will clearly have important therapeutic implications and may be a future research
      consideration in antibiotic drug design.

PMID- 9267956
TI  - Survival and functional outcome of children requiring endotracheal intubation
      during therapy for severe traumatic brain injury.
AB  - OBJECTIVE: To determine the predictors of survival and functional outcome of
      pediatric patients with traumatic brain injury severe enough to require
      endotracheal intubation and mechanical ventilation. DESIGN: Retrospective,
      observational cohort study. SETTING: Pediatric intensive care unit (ICU) at a
      tertiary care children's hospital. PATIENTS: All children (n = 105) admitted over
      a 5-yr period with traumatic brain injury severe enough to require endotracheal
      intubation and mechanical ventilation. The median age was 43 months (range 1
      month to 14 yrs). Of these children, 74% were male and 70% were white.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Variables studied included
      vital signs during the first 24 hrs of admission, Pediatric Risk of Mortality
      (PRISM) score, Glasgow Coma Score, duration of mechanical ventilation, and number
      of pediatric ICU and hospital days. Functional status was graded as normal,
      independent, partially dependent, or dependent in the areas of locomotion, self
      care, and communication. This status was assessed at hospital discharge by chart
      review and at follow-up by telephone interview. The median Glasgow Coma Score was
      6 (range 3 to 14) and the median PRISM score was 13 (range 1 to 51). There were
      19 (18.1%) deaths, 17 in the pediatric ICU and two after hospital discharge. Of
      the patients who survived to hospital discharge, 39 (37.1%) patients were
      completely normal or independent, 42 (40%) patients were partially dependent, and
      seven (6.7%) patients were dependent in all three areas of function. Follow-up
      evaluations were available for 80 patients, with a median follow-up time of 24.5
      months (range 8 to 70). Of the 78 patients who survived and were available for
      follow-up, the number who were functionally normal or independent increased to 69
      (65.7%). At follow-up, there were eight (7.6%) patients remaining with partial
      dependency in at least one area of function while one (0.9%) patient continued to
      be dependent in all three areas of function. Mortality and dependent functional
      outcome were more likely in patients with younger age, lower Glasgow Coma Score,
      and higher PRISM score at hospital admission. Of the 27 patients with a Glasgow
      Coma Score of < or = 5, 11 (40.7%) survived with normal or independent functional
      status at follow-up. Of the 24 patients with PRISM scores of > 20, only five
      (20.8%) were functionally normal or independent at follow-up. The relative risk
      of a bad outcome for patients with a Glasgow Coma Score of < or = 5 and a PRISM
      score of > or = 20 was ten times higher than the group of patients with a Glasgow
      Coma Score of < or = 5 but a PRISM score of < 20. CONCLUSIONS: Children with
      severe traumatic brain injury who survive to hospital discharge will continue to
      improve in their functional status over the next few years. Although low Glasgow
      Coma Score is strongly associated with death or poor functional outcome after
      therapy for traumatic brain injury, many patients with Glasgow Coma Score of < or
      = 5 can survive with good function. PRISM scores add to the power of Glasgow Coma
      Score to predict survival and functional outcome in tracheally intubated
      pediatric patients with Glasgow Coma Score of < or = 5.

PMID- 9267957
TI  - Effect of hyperventilation on regional cerebral blood flow in head-injured
      children.
AB  - OBJECTIVES: To study cerebral blood flow and cerebral oxygen consumption in
      severe head-injured children and also to assess the effect of hyperventilation on
      regional cerebral blood flow. DESIGN: Prospective cohort study. SETTING:
      Pediatric intensive care unit at a tertiary-level university children's hospital.
      PATIENTS: Twenty-three children with isolated severe brain injury, whose
      admission Glasgow Coma Scores were <8. INTERVENTIONS: PaCO2 was adjusted by
      altering minute ventilation. Cerebral metabolic measurements were made at three
      levels of PaCO2 (>35, 25 to 35, and <25 torr [>4.7, 3.3 to 4.7, and <3.3 kPa])
      after allowing 15 mins for equilibrium. MEASUREMENTS AND MAIN RESULTS: Thirty
      eight studies (each study consisting of three sets of measurements at different
      levels of PaCO2) were performed on 23 patients. At each level of PaCO2, the
      following measurements were made: xenon-enhanced computed tomography scans;
      cerebral blood flow; intracranial pressure; jugular venous bulb oxygen
      saturation; mean arterial pressure; and arterial oxygen saturation. Derived
      variables included: cerebral oxygen consumption; cerebral perfusion pressure; and
      oxygen extraction ratio. Cerebral blood flow decreased below normal after head
      injury (mean 49.6 +/- 14.6 mL/min/100 g). Cerebral oxygen consumption decreased
      out of proportion to the decrease in cerebral blood flow; cerebral oxygen
      consumption was only a third of the normal range (mean 1.02 +/- 0.59 mL/min/100
      g). Neither cerebral blood flow nor cerebral oxygen consumption showed any
      relationship to time after injury, Glasgow Coma Score at the time of
      presentation, or intracranial pressure. The frequency of one or more regions of
      ischemia (defined as cerebral blood flow of <18 mL/min/100 g) was 28.9% during
      normocapnia. This value increased to 73.1% for PaCO2 at <25 torr. CONCLUSIONS:
      Severe head injury in children produced a modest decrease in cerebral blood flow
      but a much larger decrease in cerebral oxygen consumption. Absolute hyperemia was
      uncommon at any time, but measured cerebral blood flow rates were still above the
      metabolic requirements of most children. The clear relationship between the
      frequency of cerebral ischemia and hypocarbia, combined with the rarity of
      hyperemia, suggests that hyperventilation should be used with caution and
      monitored carefully in children with severe head injuries.

PMID- 9267958
TI  - Behavior of nitric oxide infused at constant flow rates directly into a breathing
      circuit during controlled mechanical ventilation.
AB  - OBJECTIVES: This study was designed to test the hypothesis that the practice of
      infusing nitric oxide at constant flow rates directly into breathing circuits
      with intermittent (pulsatile) flow can lead to streaming and tidal pooling of the
      nitric oxide. This study was also designed to show the extent to which streaming
      and tidal pooling of nitric oxide affect nitric oxide delivery. DESIGN: A series
      of five in vitro experiments was performed. For each experiment, either one or
      two features of the nitric oxide delivery/sampling system were varied, and the
      effects of these variations were evaluated with regard to measured nitric oxide
      concentration changes. The results from each experiment were analyzed using
      either one- or two-factor analysis of variance. SETTING: University research
      laboratory. SUBJECTS: Breaths were provided by a mechanical ventilator that was
      connected to a lung model. A standard, corrugated, adult breathing circuit was
      used. Gas samples were obtained from either the lung model's bellows or selected
      sites within the breathing circuit. Nitric oxide concentrations were measured,
      using an electrochemical gas analyzer. INTERVENTIONS: The system features that
      were varied included the cross-sectional position of the sampling site within the
      breathing circuit, the distance between the infusion port and the sampling site,
      the breathing frequency, the distance between the Y-piece and the infusion port,
      and the airway (deadspace) volume. MEASUREMENTS AND MAIN RESULTS: Streaming of
      nitric oxide within the breathing circuit was detected as far as 25 cm downstream
      of the infusion site (p < .0001). Pooling of nitric oxide was detected both near
      and downstream of the infusion site (p < .0001). Increasing the breathing
      frequency from 5 to 30 breaths/min increased mixing thoroughness (p < .005).
      Increasing the distance between the Y-piece and the infusion port from 15 to 180
      cm decreased nitric oxide delivery to our lung model (p < .0001). Interestingly,
      increasing airway (deadspace) volume from 150 to 450 mL decreased nitric oxide
      delivery to our lung model (p < .0001). CONCLUSIONS: Estimates of nitric oxide
      delivery using a constant flow rate of nitric oxide infused directly into a
      breathing circuit during controlled mechanical ventilation can be confounded by
      streaming and tidal propagation of nitric oxide pools. Improved reproducibility
      of reported dose-response relationships is likely to be achieved through further
      study of nitric oxide behavior within the breathing circuits. Reduced toxicity
      associated with nitric oxide inhalation may also be achieved through a better
      understanding of this nitric oxide behavior.

PMID- 9267959
TI  - Central venous catheter replacement strategies: a systematic review of the
      literature.
AB  - OBJECTIVE: To evaluate the effect of guidewire exchange and new-site replacement
      strategies on the frequency of catheter colonization and infection, catheter
      related bacteremia, and mechanical complications in critically ill patients. DATA
      SOURCES: We searched for published and unpublished research by means of MEDLINE
      and Science Citation Index, manual searching of Index Medicus, citation review of
      relevant primary and review articles, review of personal files, and contact with
      primary investigators. STUDY SELECTION: From a pool of 151 randomized, controlled
      trials on central venous catheter management, we identified 12 relevant
      randomized trials of catheter replacement over a guidewire or at a new site. DATA
      EXTRACTION: In duplicate and independently, we abstracted data on the population,
      intervention, outcome, and methodologic quality. DATA SYNTHESIS: As compared with
      new-site replacement, guidewire exchange is associated with a trend toward a
      higher rate of catheter colonization (relative risk 1.26, 95% confidence interval
      0.87 to 1.84), regardless of whether patients had a suspected infection.
      Guidewire exchange is also associated with trends toward a higher rate of
      catheter exit-site infection (relative risk 1.52, 95% confidence interval 0.34 to
      6.73) and catheter-related bacteremia (relative risk 1.72, 95% confidence
      interval 0.89 to 3.33). However, guidewire exchange is associated with fewer
      mechanical complications (relative risk 0.48, 95% confidence interval 0.12 to
      1.91) relative to new-site replacement. Exchanging catheters over guidewires or
      at new sites every 3 days is not beneficial in reducing infections, compared with
      catheter replacement on an as-needed basis. CONCLUSIONS: Guidewire exchange of
      central venous catheters may be associated with a greater risk of catheter
      related infection but fewer mechanical complications than new-site replacement.
      More studies on scheduled vs. as-needed replacement strategies using both
      techniques are warranted. If guidewire exchange is used, meticulous aseptic
      technique is necessary.

PMID- 9267960
TI  - Zidovudine-induced fatal lactic acidosis and hepatic failure in patients with
      acquired immunodeficiency syndrome: report of two patients and review of the
      literature.

PMID- 9267961
TI  - Survival put to the acid test: extreme arterial blood acidosis (pH 6.33) after
      near drowning.

PMID- 9267962
TI  - Standardizing oxygen measurements.

PMID- 9267963
TI  - Low lipid concentrations in critical illness: hypocholesterolemia among trauma
      patients.

PMID- 9267964
TI  - Central venous catheterization in a patient in the prone position.

PMID- 9267965
TI  - The distance shortening phenomenon or the lazy arm sign as a subtle pyramidal
      sign.

PMID- 9267966
TI  - Central pontine myelinolysis in a patient with classic heat stroke.

PMID- 9267967
TI  - What is the accuracy of the clinical diagnosis of multiple system atrophy? A
      clinicopathologic study.
AB  - BACKGROUND: The presentation of symptoms for multiple system atrophy (MSA)
      varies. Because there are no specific markers for its clinical diagnosis, the
      diagnosis rests on the results of the neuropathologic examination. Despite
      several clinicopathologic studies, the diagnostic accuracy for MSA is unknown.
      OBJECTIVES: To determine the accuracy for the clinical diagnosis of MSA and to
      identify, as early as possible, those features that would best predict MSA.
      DESIGN: One hundred five autopsy-confirmed cases of MSA and related disorders
      (MSA [n=16], non-MSA [n=89]) were presented as clinical vignettes to 6
      neurologists (raters) who were unaware of the study design. Raters identified the
      main clinical features and provided a diagnosis based on descriptions of the
      patients' first and last clinic visits. METHODS: Interrater reliability was
      evaluated with the use of kappa statistics. Raters' diagnoses and those of the
      primary neurologists (who followed up the patients) were compared with the
      autopsy-confirmed diagnoses to estimate the sensitivity and positive predictive
      values at the patients' first and last visits. Logistic regression analysis was
      used to determine the best predictors to diagnose MSA. RESULTS: For the first
      visit (median, 42 months after the onset of symptoms), the raters' sensitivity
      (median, 56%; range, 50%-69%) and positive predictive values (median, 76%; range,
      61%-91%) for the clinical diagnosis of MSA were not optimal. For the last visit
      (74 months after the onset of symptoms), the raters' sensitivity (median, 69%;
      range, 56%-94%) and positive predictive values (median, 80%; range, 77%-92%)
      improved. Primary neurologists correctly identified 25% and 50% of the patients
      with MSA at the first and last visits, respectively. False-negative and -positive
      misdiagnoses frequently occurred in patients with Parkinson disease and
      progressive supranuclear palsy. Early severe autonomic failure, absence of
      cognitive impairment, early cerebellar symptoms, and early gait disturbances were
      identified as the best predictive features to diagnose MSA. CONCLUSIONS: The low
      sensitivity for the clinical diagnosis of MSA, particularly among neurologists
      who followed up these patients in the tertiary centers, suggests that this
      disorder is underdiagnosed. The misdiagnosis of MSA is usually due to its
      confusion with Parkinson disease or progressive supranuclear palsy, thus
      compromising the research on all 3 disorders.

PMID- 9267968
TI  - Cognitive sequelae of unilateral posteroventral pallidotomy.
AB  - OBJECTIVE: To examine the cognitive sequelae of unilateral posteroventral
      pallidotomy. DESIGN: Single-group pretest and posttest methodologic assessment
      with baseline evaluation performed 1 to 2 days prior to surgery and follow-up
      conducted 3 months after pallidotomy. SETTING: Movement disorder clinic at a
      university medical center. PATIENTS: Fourteen patients (age range, 43-82 years)
      with Parkinson disease (average disease duration, 7.4 years). INTERVENTION:
      Unilateral posteroventral pallidotomy procedures were performed on the right
      (n=8) and left (n=6) side of the brain. MAIN OUTCOME MEASURES: The protocol
      consisted of a range of neuropsychological instruments sensitive to subcortical
      dysfunction, including measures of bi-manual coordination, simple-complex
      reaction time, visual attention, naming, verbal fluency, learning, recognition
      memory, and problem solving. RESULTS: No significant deterioration in specific
      cognitive abilities was observed as a function of the procedure. Patients showed
      a significant improvement in motor coordination speed for both contralateral and
      ipsilateral upper extremities. CONCLUSIONS: Stereotactic unilateral
      posteroventral pallidotomy is associated with minimal risk of adverse
      neuropsychological effects or cognitive decline. Additional research is
      warranted, with an increased sample size and extended follow-up, to assess any
      potential lateralized effects of the procedure.

PMID- 9267969
TI  - Presence of herpes simplex DNA in surgical tissue from human epileptic seizure
      foci detected by polymerase chain reaction: preliminary study.
AB  - OBJECTIVES: To determine whether herpes simplex virus causes monofocal epilepsy
      and to assess the presence of herpes simplex virus 1 (HSV-1) and HSV-2 in
      surgical specimens from patients with epilepsy by using polymerase chain reaction
      and Southern blot analysis. BACKGROUND: Herpes simplex virus is a common
      neurotropic virus capable of latency within the central nervous system; it has a
      predilection for the temporal lobe. Central nervous system infection with HSV has
      been associated with seizure activity. DESIGN AND METHODS: Surgical specimens
      were removed from 50 patients as part of a treatment protocol for monofocal
      epilepsy. Neuropathological classification was done, and adjacent sections were
      screened for HSV by using polymerase chain reaction. Tissues obtained post mortem
      from the temporal lobe cortex of persons with Alzheimer disease (n=17), Parkinson
      disease (n=14), or nonneurological disease (n=17) served as controls. RESULTS:
      Twenty (40%) of the 50 epilepsy cases and 2 (4%) of the 48 control cases had at
      least one sample that tested positive for HSV (P<.001). Sixty-seven percent
      (8/12) of the epilepsy cases with heterotopia were positive for HSV. CONCLUSIONS:
      There was a statistically significant difference in the frequency of HSV-positive
      surgical specimens from monofocal seizure epicenters compared with nonepilepsy
      control specimens. These data suggest an association of the virus with seizure
      activity. All specimens positive for HSV (surgical specimens and control
      specimens) should be examined to determine the activity or latency state of the
      virus and cellular localization.

PMID- 9267970
TI  - Magnetic resonance imaging measurement of the caudate nucleus in adolescents with
      attention-deficit hyperactivity disorder and its relationship with
      neuropsychological and behavioral measures.
AB  - OBJECTIVE: To investigate structural basal ganglia abnormalities in attention
      deficit hyperactivity disorder (ADHD) and their relationship with the
      neuropsychological deficits and behavioral problems found in ADHD. DESIGN: Case
      control study. SETTING: Adolescents were recruited from a local polytechnic
      institute of secondary education. SUBJECTS: Eleven adolescents with ADHD and 19
      healthy control subjects. Subjects with ADHD were diagnosed by the school
      psychologist from a total population of 450 students according to the Diagnostic
      and Statistical Manual of Mental Disorders, Third Edition, Revised. Diagnosis was
      confirmed by the Conners Teachers Rating Scale and a structured family interview.
      MAIN OUTCOME MEASURES: Magnetic resonance imaging single-slice transversal
      measurements of the head of the caudate nucleus and a comprehensive
      neuropsychological evaluation, which was specially designed to assess frontal
      striatal functioning. RESULTS: The ADHD group had a larger right caudate nucleus
      area than the control group. In control adolescents, larger caudate nucleus areas
      were associated with poorer performance on tests of attention and higher ratings
      on the Conners Teachers Rating Scale. CONCLUSIONS: These findings provide further
      evidence of the involvement of the caudate nucleus in the neuropsychological
      deficits and behavioral problems found in ADHD. The larger caudate nucleus found
      in the ADHD group could be related to a failure of the maturational processes
      that normally result in volume reduction.

PMID- 9267971
TI  - Extrapyramidal signs in patients with probable Alzheimer disease.
AB  - OBJECTIVE: To examine whether extrapyramidal signs (EPSs) were associated with
      more rapid progression of Alzheimer disease (AD). DESIGN: Cross-sectional with
      longitudinal follow-up and the likelihood of arriving at 4 end points: Mini
      Mental State Examination score of less than 9, Blessed Dementia Rating Scale
      score for activities of daily living of 15 or more, institutionalization, and
      death using a proportional hazard model with 6 variables: overall EPSs,
      bradykinesia, tremors, abnormal gait, cogwheel rigidity, and postural
      instability. SETTING: Multidisciplinary behavioral neurology research clinic.
      PATIENTS: We examined the individual EPS characteristics of 164 patients with
      mild-moderately probable AD, free of neuroleptic medication, participating in a
      longitudinal study of dementia. RESULTS: Patients with AD with EPSs (n= 51 [31%])
      were older (P>.001) and had lower Mini-Mental State Examination scores (P=.003)
      than those without EPSs at study entry. Bradykinesia was present in 35 (69%) of
      the 51 patients with EPSs, abnormal gait in 18 (35%), rigidity in 10 (20%),
      postural instability in 10 (20%), tremors in 7 (14%), and oral-mandibular
      dyskinesia in 2 (4%). Using proportional hazard analysis with time-dependent
      covariates for overall EPSs and individual EPSs, adjusted by age at study entry,
      education, Mini-Mental State Examination score, and Blessed Dementia Rating Scale
      score for activities of daily living, the development of EPSs was associated with
      time to institutionalization (P<.001) but not with cognitive (eg, Mini-Mental
      State Examination score <9) or functional (eg, Blessed Dementia Rating Scale
      score > or = 15) decline or death. However, when we examined severity of the
      EPSs, as measured by the New York University Parkinson's Disease Scale, the
      development of EPSs was associated with functional decline (P=.005). Of the
      individual EPSs, rigidity predicted death (P<.001) and institutionalization
      (P=.03), whereas tremors predicted functional decline (P=.02). CONCLUSIONS: In
      this cohort, the presence or absence of EPSs is related to time to
      institutionalization, but not to severe cognitive or functional impairment or
      death. However, when severity of the extrapyramidal phenomenon is taken into
      account, EPSs are related to functional decline. Further, it appears that a
      subgroup of patients with AD with EPSs, where cogwheel rigidity and tremors are
      the core signs, can have a worse outcome.

PMID- 9267972
TI  - Balance in the healthy elderly: posturography and clinical assessment.
AB  - OBJECTIVES: To measure balance changes in the healthy elderly using quantitative
      dynamic posturography. To relate these changes to clinical measures of balance
      and gait. DESIGN: Elderly subjects screened for health criteria in a longitudinal
      study were examined using standardized cognitive, neurological, and performance
      based tests. Quantitative posturography (Equitest, Neurocom International,
      Clackamas, Ore) was performed to determine the subject's response to sensory
      (Sensory Organization Test) and motor perturbations (Motor Coordination Test).
      SUBJECTS: Thirty-three healthy, old old subjects (> or =80 years; mean+/-SD age,
      88+/-5 years) were compared with 15 subjects younger than 80 years (mean+/-SD
      age, 72+/-3 years). All were free of centrally active medications. RESULTS: The
      old old had worse quantitative equilibrium scores compared with subjects younger
      that 80 years when proprioceptive input was inaccurate and visual input was
      either preserved or completely absent. Old old subjects showed diminished
      adaptation to repeated platform rotations and fell more frequently during
      posturography. Quantitative balance measures correlated with age and functional
      measures of balance (Tinetti Balance Scale score, timed 1 leg standing).
      CONCLUSIONS: Progressive, functionally evident, age-related quantitative balance
      changes occur independent of typical geriatric pathological changes. These data
      should facilitate clinical decisions by allowing the distinction to be made
      between age-related and pathological changes.

PMID- 9267973
TI  - Cognitive functions in major depression and Parkinson disease.
AB  - OBJECTIVE: To investigate the importance of major depression in the production of
      cognitive deficits in patients with Parkinson disease (PD). DESIGN: A
      comprehensive neuropsychological and psychiatric assessment was conducted in 19
      patients with PD and major depression, 31 patients with PD without depression, 27
      patients with major depression but without PD, and 12 age-comparable healthy
      controls. SETTING: Outpatient clinic. RESULTS: Patients with major depression
      (with or without PD) had significantly more severe cognitive deficits than both
      healthy controls and patients with PD without depression on tests of verbal
      fluency and auditory attention, while patients with PD and major depression had
      significantly more severe deficits on tasks of abstract reasoning and set
      alternation compared with the other 3 groups. CONCLUSIONS: Major depression in
      patients with PD is associated with significant deficits on specific cognitive
      tasks. While some of these deficits may be explained by the presence of major
      depression, frontal lobe-related cognitive impairments may result from an
      interaction between neuropathologic factors in PD and the mechanism of major
      depression.

PMID- 9267974
TI  - Olfactory dysfunction for pyridine and dementia progression in Alzheimer disease.
AB  - OBJECTIVE: To investigate whether odor detection sensitivity for pyridine,
      suggested by previous research not to be affected, is impaired in Alzheimer
      disease (AD) and whether an association exists between odor threshold and both
      degree of dementia and rate of dementia progression in AD. METHOD: The method of
      constant stimuli was used to determine odor thresholds for pyridine in 18
      patients with AD (Diagnostic and Statistical Manual of Mental Disorders, Third
      Edition, Revised and National Institute of Neurological and Communicative
      Disorders and Stroke-Alzheimer's Disease and Related Disorders Association
      criteria) and 16 healthy elderly control subjects. All participants were
      carefully examined with medical and neuropsychological tests. RESULTS: Six
      patients with AD but none of the controls were anosmic (total olfactory loss) to
      pyridine, and the 12 nonanosmic patients had significantly higher detection
      thresholds (50% probability for detection, 323 parts per billion [ppb]) than did
      the controls (50% probability for detection, 105 ppb). In addition, an
      association was found between odor threshold and both degree of dementia and rate
      of dementia progression in AD. CONCLUSIONS: In contrast to previous findings, our
      results provide evidence that odor sensitivity in AD is impaired for pyridine.
      Odor sensitivity, in addition to other suggested predictors of progression rate,
      may be of interest for defining subgroups of AD or for clinical prognostic
      judgments of single patients.

PMID- 9267975
TI  - Classification and staging of dementia of the Alzheimer type: a comparison
      between neural networks and linear discriminant analysis.
AB  - OBJECTIVE: To examine the utility of artificial neural networks (ANNs) for
      differentiating patients with Alzheimer disease from healthy control subjects and
      for staging the degree of dementia. DESIGN: Comparison of the classification
      abilities of ANNs with the statistical technique of linear discriminant analysis
      (LDA) using the results of 11 neuropsychological tests as predictors.
      PARTICIPANTS: Ninety-two patients with a diagnosis of probable Alzheimer disease
      (referred from a geriatric clinic) and 43 elderly control subjects (independently
      solicited). The patients met National Institute of Neurological and Communicative
      Disorders and Stroke-Alzheimer's Disease and Related Disorders Association
      criteria for probable dementia, with clinical ratings of dementia severity
      derived from the Cambridge Examination for Mental Disorders of the Elderly
      (CAMDEX). MAIN OUTCOME MEASURES: Classifications between and within groups were
      determined by using LDA and ANNs, and more detailed comparisons of the 2 methods
      were performed by using chi2 analyses and unweighted and weighted kappa
      statistics. RESULTS: Linear discriminant analysis correctly identified 71.9% of
      cases. Artificial neural networks, trained to classify the subjects using the
      same data, correctly classified 91.1% of the cases. Subsidiary analyses showed
      that although both techniques effectively discriminated between the control
      subjects and patients with dementia, the ANNs were more powerful in
      discriminating severity levels within the dementia population. The analyses for
      goodness of fit revealed that the ANN classification produced a better fit to the
      actual data. A comparison of the weighted proportion of agreement between the
      criterion and predictor variables also showed that the ANNs clearly outperformed
      LDA in classification accuracy for the full data set and patients-only data set.
      CONCLUSION: The results demonstrate the utility of ANNs for group classification
      of patients with Alzheimer disease and elderly controls and for staging dementia
      severity using neuropsychological data.

PMID- 9267976
TI  - Serum angiotensin-converting enzyme in multiple sclerosis.
AB  - OBJECTIVE: To determine the extent and significance of serum angiotensin
      converting enzyme (ACE) elevation in multiple sclerosis (MS) and the correlation
      between serum ACE activity and clinical and magnetic resonance imaging (MRI)
      indicators of disease activity. DESIGN: A retrospective cross-sectional study of
      45 consecutive patients with clinically definite MS and a longitudinal study of
      30 additional patients with clinically definite MS involved in a long-term study
      of neurologic function and MRI in MS. SETTING: Comprehensive MS center of a
      tertiary care university hospital. SUBJECTS: A total of 75 patients with
      clinically definite MS and 31 healthy controls. METHODS: Serum ACE activity was
      measured using a spectrophotometric assay and correlated with clinical indicators
      of disease activity and with total cerebral MS lesion volume measured by MRI.
      RESULTS: An elevated ACE activity was found in 17 (23%) of 75 patients with MS as
      compared with 2 (6%) of 31 healthy controls. Changes in serum ACE activity
      correlated with changes in total plaque volume on MRI. CONCLUSIONS: Serum ACE
      activity may be an indicator of disease activity in longitudinal analysis. Also,
      elevated ACE activity in a patient with otherwise typical MS need not raise
      suspicions of alternative diagnoses.

PMID- 9267977
TI  - Serial neuropsychological assessment and magnetic resonance imaging analysis in
      multiple sclerosis.
AB  - OBJECTIVE: To assess the correlation between cognitive dysfunction and disease
      burden in multiple sclerosis (MS) during a 1-year period. DESIGN: The Brief,
      Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis was
      performed at entrance and 1 year. Patients underwent at least 20 proton density
      (range, 20-24) and T2-weighted axial magnetic resonance imaging (MRI) brain scans
      except for stable patients who were scanned monthly. Magnetic resonance imaging
      was evaluated using computer-automated, 3-dimensional volumetric analysis.
      SETTING: A research clinic of a university hospital. PATIENTS: Forty-four
      patients with MS of the following disease categories: relapsing-remitting (14),
      relapsing-remitting progressive (12), chronic progressive (13), and stable (5).
      MAIN OUTCOME MEASURES: The relationships between scores on the Brief, Repeatable
      Battery of Neuropsychological Tests in Multiple Sclerosis and 2 MRI measures
      (total lesion volume and brain to intracranial cavity volume ratio) were assessed
      using linear regression. These MRI measures were also compared with cognitive
      status at 1 year using analysis of variance. RESULTS: Overall, there was no
      decline in mean cognitive test performance during 1 year. Significant
      correlations were found between baseline neuropsychological test scores of
      nonverbal memory, information-processing speed, and attention and both MRI
      measures. Patients with chronic progressive MS demonstrated the strongest
      correlations. At 1 year, change in information-processing speed and attention
      correlated with change in total lesion volume. The mean increase in total lesion
      volume was 5.7 mL for 4 patients whose cognitive status worsened compared with
      0.4 mL for 19 patients who improved and 0.5 mL for 21 patients who remained
      stable. CONCLUSIONS: During a 1-year period mean cognitive performance did not
      worsen. Automated volumetric MRI measures of total lesion volume and brain to
      intracranial cavity volume ratio correlated with neuropsychological performance,
      especially in patients with chronic progressive MS. Worsening MRI lesion burden
      correlated with cognitive decline.

PMID- 9267978
TI  - Posteroventral medial pallidotomy in levodopa-unresponsive parkinsonism.
AB  - BACKGROUND: Parkinsonism in a 42-year-old patient, which was presumably related
      to peripheral trauma, did not respond to levodopa therapy. OBSERVATION: We
      treated the patient with microelectrode-guided unilateral posteroventral medial
      pallidotomy and followed up with magnetic resonance imaging and prospective
      clinical evaluation. Pallidotomy resulted in marked improvement of right-sided
      parkinsonian symptoms and functional disability at 4.5 months after surgery.
      Microelectrode recording during pallidotomy revealed discharge patterns that were
      similar to those seen in patients with Parkinson disease. Postoperative magnetic
      resonance imaging confirmed the location of the lesion in the posteroventral
      medial pallidum. CONCLUSIONS: Posteroventral pallidotomy usually has limited
      benefit in patients with degenerative atypical parkinsonism who do not respond to
      levodopa therapy. Nevertheless, pallidotomy can be an effective treatment for
      other levodopa-unresponsive parkinsonian disorders.

PMID- 9267979
TI  - Can we treat respiratory failure in Friedreich ataxia?
AB  - BACKGROUND: Neurochemical disorders associated with spinocerebellar ataxias are
      multiple. OBJECTIVE: To use replacement and neuroprotective therapy in a case of
      severe respiratory failure in Friedreich ataxia. PATIENT AND TREATMENT: A 44-year
      old man with severe Friedreich ataxia displayed arduous periodic breathing
      associated with minor desaturation as well as obstructive or mixed apneas
      associated with severe desaturation during the night. He was given oxitriptan (5
      hydroxy-L-tryptophan) (1500 mg/d), thiamine hydrochloride (100 mg/d), and
      amantadine hydrochloride (100 mg/d). The first sleep study was conducted during
      the night before treatment, whereas the second was performed during the night
      after 9 months of treatment. RESULTS: After treatment, striking clinical
      improvement of spastic dysphonia was accompanied by significant diminution in the
      time spent in periodic breathing and in the number of obstructive and mixed
      apneas during the night. Controlled studies are needed.

PMID- 9267980
TI  - Ontogenic changes in proglucagon mRNA in BB diabetes prone and normal rats weaned
      onto a chow diet.
AB  - Weaning onto chow diets causes the highest incidence of diabetes in the BB rat.
      Changes in gut development and absorption of nutrients in the diabetes prone rat
      and the subsequent effect on pancreatic function may play a role in the ultimate
      development of the disease. BB diabetes prone (dp) and BB normal (n) dams were
      fed chow diets. Pups were killed at various ages ranging from 7 to 30 days. BBdp
      rats had higher small intestine and colon weights expressed per body weight at
      all ages (p < 0.0001). RNA content (mg/g) in the jejunum, ileum and colon was
      higher in the BBdp rats beginning at the critical period at 21 days and
      maintained at 24 days and 30 days (p < 0.0001). Proglucagon message decreased
      with age in both BBdp and BBn animals (p < 0.0001). Levels of proglucagon mRNA
      were higher in BBdp compared to BBn animals only in the ileum at 10 days (p <
      0.01). Adjusting for total ileal and colonic RNA content resulted in BBdp animals
      having higher total colonic proglucagon mRNA at 21, 24 and 30 days (p < 0.0001).
      Plasma GLP-1(7-36) amide was more than doubled in BBdp compared to BBn animals (p
      < 0.0005) at 30 days. Expressing sodium-dependent D-glucose co-transporter (SGLT
      1), GLUT2 and GLUT5 mRNA per total jejunal RNA shows increased transporter mRNA
      in BBdp compared to BBn rats at weaning (21 days) (p < 0.05). Radical differences
      exist between BBdp and BBn animals at 'critical periods' in both proglucagon and
      glucose transporter gene expression. These differences may help explain altered
      growth and diseases incidence between these two strains.

PMID- 9267981
TI  - Cytoskeletal changes induced by excess extracellular matrix impair endothelial
      cell replication.
AB  - Thickening of basement membranes is an early and characteristic feature of
      diabetic vessels, but its consequences on the properties of vascular cells remain
      undefined. We investigated whether and how excess extracellular matrix (ECM)
      alters the replication of vascular endothelial cells in vitro. To test the
      effects of endogenous excess matrix, human umbilical vein endothelial cells
      (HUVEC) were plated on ECM produced under culture conditions (high ambient
      glucose) that increase ECM synthesis. Four of six HUVEC isolates plated on such
      ECM yielded a lower cell number (68 +/- 18%) than cells plated on control ECM.
      Growth inhibition was observed in HUVEC cultured on elevated concentrations (10
      and 50 microg/ml) of exogenous fibronectin, when compared with HUVEC plated on
      tissue culture plastic or 0.25, 1.0, and 5.0 microg/ml fibronectin; the decreased
      replication was attributable to delayed transit through the G1 phase of the cell
      cycle. HUVEC grown on both 1 and 10 microg/ml fibronectin exhibited a modest
      upregulation of the fibronectin-specific integrin receptor alpha5beta1, and
      increased attachment to fibronectin substratum. However, unique to the HUVEC
      plated on growth-inhibitory concentrations of fibronectin was a redistribution in
      situ of integrins and vinculin to form more numerous focal adhesions, and an
      increased polymerization of cytoskeletal actin to form stress fibers.
      Concentrations (0.01 microg/ml) of cytochalasin D intended to prevent excess
      actin polymerization prevented the growth inhibition. Thus, excess ECM hampers
      endothelial cell replication in vitro through increased cell-ECM adhesion and
      attendant cytoskeletal rearrangements. These phenotypic changes provide probes to
      test whether cell-ECM interactions are altered in diabetic vessels in a direction
      that may compromise orderly endothelial cell renewal and its antithrombogenic
      function.

PMID- 9267982
TI  - Expression of gastrin and transforming growth factor-alpha during duct to islet
      cell differentiation in the pancreas of duct-ligated adult rats.
AB  - In adult rats islet cell neogenesis can be stimulated by partial duct ligation.
      Duct to islet cell differentiation is thought to be regulated by growth factors
      such as gastrin and transforming growth factor-alpha (TGF alpha). To test this
      hypothesis, we examined the expression of gastrin and TGF alpha at the mRNA and
      protein level in pancreatic tissue following partial duct ligation. Pancreatic
      specimens were investigated on days 3, 5, 7 and 14 after duct ligation by means
      of non-isotopic in situ hybridization, immunocytochemistry and Western blotting.
      Gastrin mRNA was strongly expressed in newly developed duct-like cell structures
      in the ligated tail portion of the pancreas before the period of pronounced islet
      cell neogenesis (days 5 and 7), and immunostaining for gastrin peptides was
      positive at days 5-7. In the non-ligated head portion and in control pancreases,
      gastrin was not expressed. Expression of TGF alpha was found to be increased in
      the ligated tail portion of the pancreas on day 3 and particularly on day 5,
      while there was no enhanced signal in the non-ligated part. Western blotting
      revealed two different TGF alpha isoforms (18 kDa and 42 kDa) in the ligated tail
      part and three isoforms (18 kDa, 24 kDa and 42 kDa) in the non-ligated head part
      and in untreated pancreases. The induction of gastrin and TGF alpha expression
      preceded the peak in the bromodeoxyuridine pulse labelling index of beta cells,
      known from a previous study to occur on day 7. We conclude that pancreas duct
      ligation induces the overexpression of gastrin and TGF alpha in the first days
      following ligation. Since ductal cells are known to give rise to endocrine cells
      after duct ligation, gastrin and TGF alpha may play a role as growth factors in
      islet neogenesis.

PMID- 9267983
TI  - Fatty acid induced insulin resistance in rat-1 fibroblasts overexpressing human
      insulin receptors: impaired insulin-stimulated mitogen-activated protein kinase
      activity.
AB  - Saturated fatty acids cause insulin resistance but the underlying molecular
      mechanism is still unknown. We examined the effect of saturated nonesterified
      fatty acids on insulin binding and action in transfected Rat-1 fibroblasts, which
      over-expressed human insulin receptors. Incubation with 1.0 mmol/l palmitate for
      1-4 h did not affect insulin binding, insulin receptor autophosphorylation,
      insulin-stimulated tyrosine kinase activity toward poly(Glu4:Tyr1), pp185 and Shc
      phosphorylation and PI3-kinase activity in these cells. However, the dose
      response curve of insulin-stimulated glucose transport was right-shifted.
      Palmitate inhibited the maximally insulin-stimulated mitogen activated protein
      (MAP) kinase activity toward synthetic peptide to 7% that of control. The
      palmitate treatment influenced neither cytosolic protein kinase A activity nor
      cAMP levels. These results suggested that 1) palmitate did not inhibit the early
      steps of insulin action from insulin binding to pp185 or Shc phosphorylation but
      inhibited insulin-stimulated MAP kinase, and that 2) palmitate decreased insulin
      sensitivity as manifested by inhibited insulin-stimulated glucose uptake. In
      conclusion, the mechanism of saturated non-esterified fatty acid induced insulin
      resistance in glucose uptake may reside at post PI3-kinase or Shc steps,
      including the level of MAP kinase activation.

PMID- 9267984
TI  - Oral insulin for diabetes prevention in NOD mice: potentiation by enhancing Th2
      cytokine expression in the gut through bacterial adjuvant.
AB  - Oral administration of insulin suppresses the development of diabetes in nonobese
      diabetic (NOD) mice and deviates the cytokine balance in the islets of Langerhans
      from a Th1 to a Th2 type cytokine pattern. However, the effect of oral insulin is
      limited and disease suppression is limited to a narrow dose range. Therefore we
      tried to improve the outcome of suboptimal insulin dosing by bacterial adjuvant.
      Mice treated with a suboptimal dose of oral insulin showed no change in diabetes
      incidence although a shift from Th1 towards Th2 cytokine expression occurred in
      inflamed islets. Significant suppression of diabetes development was only seen in
      NOD mice receiving both, insulin and the bacterial preparation OM-89 as adjuvant.
      OM-89 is a protein extract of Escherichia coli, with nonspecific
      immunostimulatory properties. Potentiation of the effect of oral insulin by the
      adjuvant was associated with upregulation of interleukin (IL)-4 Th2 cells in
      infiltrated islets and sustained local IL-2 gene expression. RT PCR analyses of
      cytokine expression in the gut showed a clear deviation to Th2 type reactivity
      and downregulation of inducible nitric oxide (NO) synthase (iNOS) expression by
      the bacterial adjuvant but not by oral insulin alone. Since macrophages are the
      primary target cells of adjuvant action we tested its effect on mouse macrophages
      in vitro. Treatment with OM-89 induced transient release of tumour necrosis
      factor alpha and nitrite but rendered macrophages refractory to restimulation by
      the potent macrophage activator lipopolysaccharide. In conclusion, the protective
      effect of oral insulin can be potentiated by pretreatment with the bacterial
      adjuvant OM-89. This effect correlates with enhanced Th2 cytokine and decreased
      iNOS gene expression in the gut, probably due to the downregulation of
      proinflammatory mediators by exposure to the adjuvant.

PMID- 9267985
TI  - Reversal by L-arginine of a dysfunctional arginine/nitric oxide pathway in the
      endothelium of the genetic diabetic BB rat.
AB  - We examined the effects of acute supplementation with arginine in vitro on
      endothelium-dependent relaxation in aortic rings taken from female genetic,
      diabetes-prone BB rats. Sensitivity to norepinephrine-induced contraction was
      unaltered in rings of diabetic BB rats compared to rings from non-diabetic
      littermates. In precontracted rings, acetylcholine produced a concentration
      dependent relaxation which was impaired by diabetes. This relaxation was blocked
      by L-nitroarginine in both control and diabetic rings. Addition of 3 mmol/l L
      arginine (but not D-arginine) enhanced relaxation in diabetic rings similar to
      that seen in control rings without arginine. L-arginine had no effect on
      acetylcholine-induced relaxation in control rings. In contrast, relaxation
      induced by nitroglycerin in diabetic rings without endothelium was not altered by
      L-arginine treatment. Thus, a defect in the utilization of arginine by nitric
      oxide synthase exists in the endothelium of the diabetic BB rat.

PMID- 9267986
TI  - Impaired development of pancreatic beta-cell mass is a primary event during the
      progression to diabetes in the GK rat.
AB  - In the endocrine pancreas of the GK rat, a genetic model of non-insulin-dependent
      diabetes mellitus (NIDDM), it is not clear whether the histopathological changes
      reported up to now are related to the pathogenesis of hyperglycaemia or whether
      they occur secondarily to metabolic alterations. Using GK rats from the Paris
      colony, our study chronicles for the first time the pathophysiologic changes that
      occur in the GK pancreas from the late fetal period (day 21.5) until adult age
      (18 weeks). As compared to Wistar controls, GK fetuses exhibited higher plasma
      glucose level, lower plasma insulin level and normal plasma glucagon level. Their
      pancreatic insulin content and the relative volume and the total mass of their
      beta cells were sharply decreased, representing only 23, 38 and 23% of control
      values, respectively. During the period from 4 days to 14 days after birth, GK
      neonates exhibited normal basal plasma glucose and glucagon levels despite
      decreased plasma insulin level. Their pancreatic insulin content represented only
      31-40% of values found in the age-related control pancreases and their total beta
      cell mass was only 35% on day 4, 30% on day 7 and 37% on day 14. The adult
      diabetic GK rats exhibited higher basal plasma glucose and insulin levels while
      their basal plasma glucagon level remained normal. Their pancreatic insulin
      content and the total beta-cell mass remained decreased, representing only 32%
      and 47% of control values, respectively. Moreover, the adult GK pancreases
      exhibited noticeable alteration in the architecture of the large islet
      subpopulation which displayed considerable fibrosis with clusters of beta cells
      widely separated from each other by strands of connective tissue. Concerning the
      development of alpha cells in the GK rats, their relative volume was found to be
      normal during fetal and early neonatal periods. It was found to be moderately
      decreased (representing 64-67% of corresponding control values) in 14-day-old
      neonates and adult GK rats. Our findings demonstrate that in the GK rat, the
      deficit of total beta-cell mass as observed in the adult animal is related to
      impaired beta-cell development. The restriction of the beta-cell mass must be
      considered as a primary and crucial event in the sequence leading to overt
      diabetes in this NIDDM model.

PMID- 9267987
TI  - Intensified insulin therapy and the risk of severe hypoglycaemia.
AB  - The objectives of the present analyses were to assess the association between
      HbA1c levels and severe hypoglycaemia (SH, treatment with glucose i.v. or
      glucagon injection) and to identify predictors of SH in a prospective multicentre
      trial. The study population consisted of 636 insulin-dependent diabetic patients
      who had participated in a structured 5-day in-patient group treatment and
      teaching programme for intensification of insulin therapy (ITTP) in one of 10
      hospitals and who were re-examined after 1, 2, 3, and 6 years including
      assessment of demographic, disease and treatment related parameters, diabetes
      related knowledge, behaviour, and emotional coping. At baseline, age (mean +/-
      SD) was 27 +/- 7 years, diabetes duration 9 +/- 7 years and HbA1c 8.3 +/- 1.9 %.
      During the 6-year follow-up, the mean HbA1c value improved to 7.6%, and in
      patients with a diabetes duration of more than 1 year at entry into the study (n
      = 538) the incidence of SH decreased from 0.28 cases/patient/year during the year
      preceding the ITTP to 0.17 cases/patient/year. The patient group was divided into
      decile groups according to mean follow-up HbA1c values. In each group more than
      230 patient years could be analysed. Groups with mean HbA1c values of 5.7, 7.0,
      7.4, 7.7 and 8.9% had comparable risks of SH (0.15-0.19 cases/patient/year). In a
      logistic regression analysis, mean HbA1c during follow-up, a history of SH during
      the year preceding the ITTP, C-peptide level, emotional coping, carrying
      emergency carbohydrates (as assessed at the 1-year follow-up), and age at onset
      of diabetes were significant independent predictors of SH. The incidence of SH
      between centres varied between 0.05 and 0.27 cases/patient/year. In conclusion,
      in the present analyses no linear or exponential relationship between HbA1c and
      severe hypoglycaemia could be identified by using simple group comparisons.
      Applying complex regression analyses, various patient-related predictors of
      severe hypoglycaemia were identified.

PMID- 9267988
TI  - Antenatal risk factors for childhood diabetes mellitus; a case-control study of
      medical record data in Yorkshire, UK.
AB  - Environmental risk factors for childhood insulin-dependent diabetes mellitus
      (IDDM) have been investigated using data abstracted from the obstetric records of
      mothers participating in a population-based case-control study of children (0-15
      years) diagnosed with IDDM during 1993-1994. A univariate analysis of 196 age and
      sex matched sets (129 triplets, 67 pairs) gave significantly raised odds ratios
      (OR) for mothers over 35 years (OR 2.13, 95%CI 1.04-4.36) and the following
      exposures in pregnancy: amniocentesis (3.85, 1.34-11.04), oedema, proteinuria
      and/or hypertensive disorders (1.62, 1.03-2.54), excessive weight gain (7.12,
      1.50-33.79) and complications in labour (1.49, 1.00-2.21). The risk previously
      associated with caesarean deliveries was confirmed and the trend of increasing
      risk with age was significant. Adjusting separately for mothers with IDDM (4
      cases, 0 control subjects), parity and small for gestational age failed to have
      any influence on the pregnancy risk factors or caesarean delivery. Case mothers
      undergoing amniocentesis were significantly younger compared to their control
      counterparts (p = 0.02) and the majority were given the test to determine fetal
      maturity, late in pregnancy, rather than to identify chromosomal abnormalities.
      Oedema, proteinuria and/or hypertension conferred an increased risk throughout
      pregnancy, particularly in the first two trimesters. No specific pattern of risk
      was present for any age group. Multivariate modelling of the significant OR,
      using conditional logistic regression, retained excessive weight gain as
      significant. The overall results present a risk profile of older mothers whose
      babies may be exposed to adverse intrauterine conditions and delivery by
      caesarean section.

PMID- 9267989
TI  - Chromosomal mapping and mutational analysis of the coding region of the glycogen
      synthase kinase-3alpha and beta isoforms in patients with NIDDM.
AB  - Activation of glycogen synthesis in skeletal muscle in response to insulin
      results from the combined inactivation of glycogen synthase kinase-3 (GSK-3) and
      activation of the protein phosphatase-1, changing the ratio between the inactive
      phosphorylated state of the glycogen synthase to the active dephosphorylated
      state. In a search for genetic defects responsible for the decreased insulin
      stimulated glycogen synthesis seen in patients with non-insulin-dependent
      diabetes mellitus (NIDDM) and their glucose-tolerant first-degree relatives we
      have performed mutational analysis of the coding region of the 2 isoforms of GSK
      3alpha and GSK-3beta in 72 NIDDM patients and 12 control subjects. No structural
      changes were detected apart from a few silent mutations. Mapping of the GSK
      3alpha to chromosome 19q13.1-13.2 and the GSK-3beta to chromosome 3q13.3-q21
      outside known genetic loci linked to NIDDM further makes it unlikely that these
      genes are involved in the pathogenesis of common forms of NIDDM.

PMID- 9267990
TI  - A missense mutation of the muscle glycogen synthase gene (M416V) is associated
      with insulin resistance in the Japanese population.
AB  - Muscle glycogen synthase (GYS1) is a key enzyme of non-oxidative pathway of
      glucose metabolism that has been reported to be related to insulin resistance in
      non-insulin-dependent diabetic (NIDDM) patients. We scanned the GYS1 gene for
      mutation by single strand conformational polymorphism in 244 non-obese Japanese
      NIDDM patients and 181 non-diabetic control subjects, and found two missense
      mutations; Met to Val at position 416 in the exon 10 (M416V) and Pro to Ala at
      position 442 in the exon 11 (P442A). The P442A mutation was found in only one
      NIDDM patient treated with sulfonylureas. On the other hand, the M416V mutation
      was widely found in the Japanese population. The mutant allele frequency in the
      NIDDM patients (13.7%) was slightly higher but not statistically significant
      compared with that in non-diabetic subjects (9.7%). However, the insulin
      sensitivity index [SI: x 10(-4) x min(-1) x (microU/ml)(-1)] estimated by Minimal
      Model analysis in the NIDDM patients carrying the M416V mutation was
      significantly lower than that in those without the mutation (1.18 +/- 0.27, n =
      21 vs 2.20 +/- 0.20, n = 60, mean +/- SEM, p < 0.01). Glucose effectiveness, age,
      body mass index, and levels of glycated haemoglobin and serum lipids were not
      significantly different between the two groups. The same trend could be seen in
      non-diabetic subjects (SI: 3.70 +/- 0.46, 9 subjects with the mutation vs 5.94 +/
      0.66, 19 subjects without the mutation, p < 0.05). These findings indicate that
      the M416V mutation of the GYS1 gene is one of the factors contributing to the
      insulin resistance in the Japanese population and may play some role in the
      pathogenesis of NIDDM.

PMID- 9267991
TI  - Divergent development of autonomic and peripheral somatic neuropathies in NIDDM.
AB  - There is no information on the mutual occurrence and the development of autonomic
      and peripheral somatic neuropathies based on long-term follow-up of patients with
      non-insulin-dependent diabetes mellitus (NIDDM). We investigated the relation
      between the changes in autonomic function values and electrodiagnostic values,
      and the relation between the occurrence of autonomic neuropathy and peripheral
      somatic polyneuropathy in a group of patients with newly diagnosed NIDDM (n =
      133, aged 45-65 years) at baseline and 5 and 10 years later. Parasympathetic
      autonomic neuropathy was diagnosed on the basis of heart rate variability during
      deep-breathing and sympathetic autonomic neuropathy on the basis of fall in
      systolic blood pressure while changing from supine to standing. Polyneuropathy
      was diagnosed on the basis of both clinical criteria and electrodiagnostic
      studies (nerve conduction velocity and response-amplitude values). In 10 years 36
      patients died, mainly from cardiovascular causes. Altogether 78 patients
      completed the study. At 10 years, parasympathetic autonomic neuropathy was
      diagnosed in 61.3% of those with polyneuropathy and 66.7% of those without.
      Likewise, the frequency of sympathetic autonomic neuropathy was similar in those
      with polyneuropathy (21.9%) and those without (26.5%). The respective figures for
      combined (both parasympathetic and sympathetic) autonomic neuropathy were 10.0%
      and 18.8%. The worsening of parasympathetic and sympathetic autonomic function
      values was not related to the worsening in electrodiagnostic results with time.
      In conclusion, the development of autonomic and peripheral somatic neuropathies
      was divergent in patients with NIDDM suggesting different pathophysiological
      processes for these neuropathies.

PMID- 9267992
TI  - The beta cell glucokinase promoter variant is an unlikely risk factor for
      diabetes mellitus. Diabetes Incidence Study in Sweden (DISS).
AB  - Glucokinase plays an important role in the regulation of insulin secretion and is
      therefore an attractive candidate gene for both insulin dependent (IDDM) and non
      insulin-dependent (NIDDM) diabetes mellitus. A single G-A nucleotide polymorphism
      at the -30 position of the beta-cell specific promoter region of the glucokinase
      gene was previously associated with reduced beta-cell function. In the present
      study we analysed 268 consecutive newly diagnosed Swedish patients classified
      with either IDDM (n = 205), NIDDM (n = 31) or unclassifiable (n = 32) diabetes
      between the ages of 15 and 35 years along with a group of 158 age- and sex
      matched control subjects. The beta-cell promoter region was amplified by the
      polymerase chain reaction and the G-A variant identified by single strand
      conformational polymorphism. There was no significant difference in allele
      frequencies of G and A between any of the subject groups and likewise, no
      significant difference in the frequencies of the G/G, G/A, or A/A genotypes.
      Eight subjects were homozygous for the less common A allele, five had IDDM and
      three were control subjects. Our results suggest that the -30 beta-cell
      glucokinase promoter variant is not associated with IDDM.

PMID- 9267993
TI  - Familial components of the multiple metabolic syndrome: the ARIC study.
AB  - The association of a parental history of diabetes mellitus and hypertension with
      the multiple metabolic syndrome (MMS) was studied in a population survey of
      middle-aged adults. The eligible population was drawn from the baseline
      examination of the Atherosclerosis Risk in Communities Study, a population-based,
      bi-ethnic, multi-centre cohort study. The MMS was defined as a multivariate,
      categorical phenotype of co-occurring diabetes, hypertension, and dyslipidaemia.
      MMS cases (n = 356) were compared to disorder-free control subjects (n = 6797)
      with respect to their parental history of diabetes and hypertension. MMS cases
      were more likely to report a history of diabetes in both parents (odds ratio [OR]
      4.7, 95 % confidence interval (CI) 1.5-14.7) or a history of hypertension in both
      parents (OR 1.9, 95 % CI 1.1-3.0) than control subjects, adjusting for BMI, waist
      to-hip ratio, age, gender, and ethnicity/centre. A parental history of diabetes
      and hypertension in both parents was associated with the greatest increase in
      odds of MMS (OR 8.3, 95 % CI 3.0-22.8). A dose-response relationship between the
      number of parental disorders (one; two; three to four) and the odds of MMS was
      observed (OR 1.2, 95 % CI 0.9-1.7; OR 2.0, 95 % CI 1.4-2.8; OR 4.0, 95 % CI 2.5
      6.2). Based on the marked associations observed between a parental history of MMS
      components and the clustering of these metabolic disorders in the offspring
      generation, we conclude that genetic and/or non-genetic familial influences play
      a role in the development of the multiple metabolic syndrome.

PMID- 9267994
TI  - Allelic variation in the vitamin D receptor influences susceptibility to IDDM in
      Indian Asians.
AB  - Vitamin D has important immunomodulatory properties and prevents development of
      diabetes mellitus in an animal model of insulin-dependent diabetes (IDDM). We
      have studied the vitamin D receptor locus as a candidate for genetic
      susceptibility to IDDM in Southern Indian families. We found evidence for an
      association of one particular vitamin D receptor allele with IDDM susceptibility
      in this community. Ninety-three South Indian families consisting of available
      parents and an affected offspring were genotyped for three vitamin D receptor
      polymorphisms using the restriction enzymes TaqI, ApaI and BsmI as well as an
      adjacent microsatellite located to 12q14 (D12S85). Transmission disequilibrium
      testing analysis was used to assess preferential transmission of polymorphic
      markers and haplotypes with IDDM. There was significant excess transmission of
      vitamin D receptor alleles containing the BsmI restriction site to affected
      offspring in these families (p = 0.016). No association was found between D12S85
      and IDDM. This study suggests that a polymorphism within or close to the vitamin
      D receptor gene may modify susceptibility to IDDM in this ethnic group.

PMID- 9267995
TI  - Molecular screening of the human melanocortin-4 receptor gene: identification of
      a missense variant showing no association with obesity, plasma glucose, or
      insulin.
AB  - Disruption of the melanocortin-4 (MC-4) receptor gene in mice results in maturity
      onset obesity, hyperinsulinaemia and hyperglycaemia. These phenotypes are
      characteristic of human obesity that frequently accompanies non-insulin-dependent
      diabetes. It is therefore possible that human MC-4 receptor gene mutations
      contribute to human obesity. To test this possibility, we examined by DNA
      sequencing the entire coding region of the human MC-4 receptor gene in 40
      morbidly obese (BMI > 35 kg/m2) white British males and examined the 5'- and 3'
      flanking regions in 20 out of these obese subjects. We also sequenced all these
      regions in 10 lean (BMI < 18 kg/m2) white British males for a reference. We
      identified a single nucleotide substitution that replaces valine with isoleucine
      at codon 103, in two obese subjects in the heterozygous state. No other
      nucleotide alterations were found. The prevalence of this missense variant was
      studied in 322 white British males (190 with BMI > 28 kg/m2 and 132 with BMI < 22
      kg/m2) selected from a population-based epidemiological survey. In these
      subjects, no homozygotes for the isoleucine allele were found. The frequency of
      heterozygotes was similar (4.2 vs 4.5%) in the two groups and there was no
      significant difference in BMI, total skinfold thickness, plasma insulin and
      glucose levels between heterozygotes and codon-103 valine homozygotes in either
      group. These results suggest that coding sequence mutations in the MC-4 receptor
      gene are unlikely to be a major cause of human obesity, at least in white British
      males.

PMID- 9267997
TI  - The pathogenesis of NIDDM involves a defective expression of the GIP receptor.

PMID- 9267996
TI  - Studies of the genetic variability of the coding region of the hepatocyte nuclear
      factor-4alpha in Caucasians with maturity onset NIDDM.
AB  - Mutations in the hepatocyte nuclear factor-4alpha (HNF-4alpha) gene cause the
      type 1 form of maturity onset diabetes of the young (MODY1). To address the
      question of whether genetic variability of HNF-4alpha is associated with late
      onset non-insulin-dependent diabetes mellitus (NIDDM) we have sequenced the
      coding region and intron/exon boundaries of the gene in 36 randomly recruited
      Danish NIDDM patients. Two nucleotide substitutions that changed the sequence of
      HNF-4alpha were identified: Thr/Ile130, which has been reported previously and a
      novel Val/Met255. The Val/Met 255 mutation was found in 4 of 477 Danish NIDDM
      patients and in none of 217 glucose tolerant control subjects; thus it cannot be
      excluded that this mutation may have an impact on NIDDM susceptibility. Among 509
      NIDDM patients the allelic frequency of the Thr/Ile130 variant was 4.7% (95%
      confidence interval: 3.4-6.0%) compared to 1.9% (0.7-3.1%) among 239 control
      subjects (p = 0.008). However, in a population sample of 942 Swedish men with an
      average age of 70 years the allelic frequency of the variant was similar in 246
      men with either impaired glucose tolerance (5.6% [2.6-8.6%]) or NIDDM (5.4% [2.7
      8.1%]) as compared to 666 glucose tolerant men (5.1% [3.9-6.3%]). Also in a
      population sample of 369 young healthy Danes the prevalence of the codon 130
      variant (4.7% [3.2-6.2%]) was similar to what was found in Swedish Caucasians.
      Thus, the allelic frequency of the Thr/Ile130 variant among the control subjects
      in the Danish case-control study deviates from the prevalence in the two other
      studies which is why we consider the significant association between the codon
      130 variant and NIDDM an incidental finding. In glucose tolerant subjects the
      codon 130 variant in its heterozygous form had no major effect on glucose-induced
      insulin and C-peptide release although a tendency to a lower insulin secretion
      during an oral glucose tolerance test was seen in middle-aged subjects. In
      conclusion, variability in the coding region of the HNF-4alpha gene is not a
      common cause of NIDDM among whites of Danish ancestry. However, a Val/Met255
      mutation was found exclusively in NIDDM patients (0.8% of cases) and functional
      as well as family segregation studies are needed to determine whether this HNF
      4alpha variant is a NIDDM causing mutation.

PMID- 9267998
TI  - Body type in mitochondrial diabetes.

PMID- 9268000
TI  - N-type calcium channel blockers from a marine bacterium, Cytophaga sp. SANK
      71996.
AB  - N-(3-Acyloxyacyl)glycines were isolated as N-type calcium channel blockers from a
      marine bacterium Cytophaga sp. SANK 71996. The identification and fermentation of
      the producing strain and structure characterization of N-(3-acyloxyacyl)glycines
      by spectral analyses and chemical syntheses are described together with their
      antagonistic activities.

PMID- 9267999
TI  - Social deprivation influences illness onset in diabetic children.

PMID- 9268001
TI  - MR566A and MR566B, new melanin synthesis inhibitors produced by Trichoderma
      harzianum. I. Taxonomy, fermentation, isolation and biological activities.
AB  - New melanin synthesis inhibitors (MR566A and B) and six related known
      isocyanocyclopentenes were isolated from the fermentation broth of Trichoderma
      harzianum. The IC50 values of MR566A and B against mushroom tyrosinase were 1.72
      and 47 microM, respectively. They inhibited melanin biosynthesis in B16 melanoma
      cells with MIC values of 0.1 and 2.2 microM, respectively. Also isolated from the
      same culture extract of T. harzianum was a new oxazole (MR93B), which showed no
      inhibitory activity against mushroom tyrosinase at a concentration of 1,000
      microg/ml.

PMID- 9268002
TI  - MR566A and MR566B, new melanin synthesis inhibitors produced by Trichoderma
      harzianum. II. Physico-chemical properties and structural elucidation.
AB  - New melanin synthesis inhibitors (MR566A and B) and six related known
      isocyanocyclopentenes were isolated from the fermentation broth of Trichoderma
      harzianum, and their structures were elucidated by spectroscopic methods. The
      structures of novel isocyanides, MR566A (1) and B (2), were elucidated as 1-(3
      chloro-1,2-dihydroxy-4-isocyano-4-cyclopenten-1-yl)etha nol, 1-(1,2,3-trihydroxy
      3-isocyano-4-cyclopenten-1-yl)ethanol, respectively. The structure of novel
      oxazole, MR93B (9), was elucidated as 4-[(1Z)-3-hydroxy-2-hydroxymethyl-1-propen
      1-yl]oxazole.

PMID- 9268003
TI  - Dihydrophencomycin methyl ester, a new phenazine derivative from a marine
      Streptomycete.
AB  - The novel 5,10-dihydrophencomycin methyl ester (4) and the known microbial
      metabolites (2-hydroxyphenyl)-acetamide (1), menaquinone MK9 (II, III, VIII, IX
      H8) (2), and phencomycin (3a) were isolated from an unidentified marine
      Streptomyces sp. and the structures were elucidated by NMR methods. Compound 4
      shows weak antibiotic activity against Escherichia coli and Bacillus subtilis.

PMID- 9268004
TI  - Inhibitors of type-I interleukin-1 receptor from microbial metabolites.
AB  - We describe here the results of a screening program conducted to discover
      inhibitors of the type-I interleukin-1 receptor (IL-1RI) from samples of
      microbial origin. An innovative approach, based on automated, nonradioactive
      receptor binding assays has been employed. Specially prepared cell-free systems
      have allowed the use of high concentrations of microbial metabolites in the
      reaction mixtures with a low percentage of false positives. More than 30,000
      microbial samples from different species of soil isolates have been tested and
      two interesting activities have been purified and characterized. One of these,
      isolated from Streptomyces sp. GE48009, was identified as niphimycin, an
      antifungal agent also known as scopafungin. Preliminary evidence suggests that
      this molecule and azalomycin F, a structural analogue, inhibit IL-IRI by virtue
      of their long-chain guanidinium moiety. The other activity, isolated from
      Aspergillus sp. GE49752, was identified as flavipin, a substituted o
      phthalaldehyde.

PMID- 9268005
TI  - UCE6, a new antitumor antibiotic with topoisomerase I-mediated DNA cleavage
      activity produced by actinomycetes: producing organism, fermentation, isolation
      and biological activity.
AB  - A novel antitumor antibiotic, UCE6 (1,3,8,10,11-pentahydroxy-2-methyl-10-(2-oxo-4
      hydroxypentyl)na phthacene-5, 12-dione) with topoisomerase I-mediated DNA
      cleavage activity, was isolated from the culture broth of actinomycetes strain
      UOE6. Addition of silicone oil antifoam agent, KS69 (2%), to the fermentation
      enhanced the production of UCE6 by approximately 3 fold. A total of 1.15 g of
      UCE6 was recovered as reddish orange crystals from a 100 liter fermentation
      supplemented with 2% KS69. UCE6 exhibited growth inhibitory activity against HeLa
      S3, HCT116 and Lu-65 cells comparable to that of camptothecin.

PMID- 9268006
TI  - Isolation and characterization of 8-demethoxy steffimycins and generation of 2,8
      demethoxy steffimycins in Streptomyces steffisburgensis by the nogalamycin
      biosynthesis genes.
AB  - Streptomyces steffisburgensis (NRRL 3193, ATCC 27466) is described as a
      steffimycin producer. Steffimycin belongs to the anthracycline group of aromatic
      polyketide antibiotics. The structural analysis of the products accumulated by
      the wild type ATCC 27466 strain revealed three different forms of 8-demethoxy
      steffimycin suggesting the loss of C-8 hydroxylation/methylation activity. In our
      approach to generate new anthracycline molecules, we used this strain as a host
      in gene cloning. The genes encoding the polyketide ketoreductase and aromatase
      enzymes of nogalamycin biosynthesis caused the production of 2-demethoxy
      steffimycins in S. steffisburgensis.

PMID- 9268007
TI  - Modification of natural immunity in mice by imipenem/cilastatin.
AB  - The imipenem/cilastatin constitutes a broad spectrum beta-lactam antibiotic
      formulation, especially used in pre and post-operatory treatments for
      transplanted or drug-immunosuppresed patients. The effect of the dose and the
      duration of the treatment with imipenem/cilastatin on some parameters of natural
      immunity in BALB/c mice were examined. The treatment by intraperitoneal route
      with 1 or 2 g/70 kg/day during 7 days did not alter significantly the parameters
      tested, whereas the greater dose used (4 g/70 kg/day) had an inhibitory effect on
      peritoneal cell counts and phagocytic activity, as well as it caused an increase
      on IL-1 production and natural killer activity. The greater stimulating effect of
      innate immunity was obtained with the lowest imipenem/cilastatin dose used (0.5
      g/70 kg/day). Since this antibiotic apparently does not impair the studied innate
      immune responses at 1 or 2 g/70 kg/day, it seems to be especially suited for the
      therapy of systemic bacterial infections in immunocompromised patients.

PMID- 9268008
TI  - A new type of chemical modification of glycopeptides antibiotics: aminomethylated
      derivatives of eremomycin and their antibacterial activity.
AB  - A series of derivatives of eremomycin aminomethylated at the 7d position of the
      resorcinol ring of the amino acid No. 7 was prepared by interaction of eremomycin
      with formaldehyde and various primary and secondary amines and ammonia. The most
      active compound obtained was 7d-decylaminomethyl derivative, whose minimal
      inhibitory concentrations for clinical isolates of staphylococci are 2
      approximately 8 times lower than those of the parent antibiotic. 7d
      Decylaminomethyl derivative was also active against vancomycin-resistant VanA
      enterococci (8 microg/ml) and Neisseria gonorrhoeae (16 microg/ml).

PMID- 9268009
TI  - Structure-activity relationships of hygromycin A and its analogs: protein
      synthesis inhibition activity in a cell free system.
AB  - Several analogs of hygromycin A were tested in an Escherichia coli cell free
      protein synthesis inhibition assay and in a Serpulina hyodysenteriae whole cell
      assay. The aminocyclitol moiety is essential for antibacterial activity in both
      cell free and whole cell assays. However a 4'-O-allyl ether of hygromycin A
      aglycone showed an equivalent MIC to hygromycin A, while having a less potent
      IC50 in the cell free assay. Hence 6-deoxy-5-keto-D-arabino-hexofuranose can be
      replaced by a hydrophobic allyl group and still retain antibacterial activity.
      However, this replacement reduces the intrinsic protein synthesis inhibition
      activity. The loss of intrinsic activity with replacement by the allyl group may
      be compensated for by better transport into the bacterial cell. In addition to
      the SAR analysis, we demonstrated that the ineffectiveness of hygromycin A
      against Gram-negative enteric bacteria such as Escherichia coli is mainly due to
      the efflux mechanism (Acr A/B pump) existing widely among the enteric bacteria
      rather than the impermeable barrier of the outer membrane.

PMID- 9268010
TI  - Isolation of new anthracyclines 10-O-rhodosaminyl beta-rhodomycinone and beta
      isorhodomycinone from mild-acid treated culture of obelmycin-producing
      Streptomyces violaceus.

PMID- 9268011
TI  - Biosynthesis of albocycline: origin of the carbon skeleton.

PMID- 9268012
TI  - SNA-60-367, new peptide enzyme inhibitors against aromatase.

PMID- 9268013
TI  - A novel method for improving Streptomyces coelicolor A3(2) for production of
      actinorhodin by introduction of rpsL (encoding ribosomal protein S12) mutations
      conferring resistance to streptomycin.

PMID- 9268014
TI  - The Aspergillus nidulans lysF gene encodes homoaconitase, an enzyme involved in
      the fungus-specific lysine biosynthesis pathway.
AB  - In filamentous fungi, lysine is synthesized via the alpha-aminoadipate pathway.
      In order to gain insight into this fungus-specific pathway (to date, no genes for
      enzymes of this pathway in filamentous fungi have been cloned) the lysine
      auxotrophic mutant LysF88 of Aspergillus nidulans was studied. HPLC and 1H-NMR
      analyses revealed that LysF88 accumulated homocitric acid in the culture
      supernatant. In addition, both the LysF88 mutant strain and LysF deletion strain
      (LysFKO) described here showed hardly any homoaconitase activity, indicating that
      lysF encodes homoaconitase. The lysF gene was cloned by complementation of the
      LysF88 mutant and sequenced. It has a size of 2397 bp, including a single intron
      of 72 bp. The two exons encode an open reading frame (ORF) of 2325 bp. The
      calculated M(r) of the homoaconitase protein (775 amino acids) is 83,943. A major
      and a minor transcript begin at positions -28 and -32, respectively. The 3' end
      of the lysF cDNA showed a poly(A) tail commencing at position +2647 following a
      250 bp untranslated region after the lysF stop codon. A putative polyadenylation
      signal sequence (TATAAA) is located 49 bp upstream of the polyadenylation site.
      Computer analysis revealed 55% amino acid sequence identity between the products
      of the putative homoaconitase ORF of A. nidulans and that of the recently
      sequenced homologous Saccharomyces cerevisiae. The similarity was particularly
      obvious in a region of cysteine residues, which are characteristic of an iron
      sulfur cluster, implying that homoaconitase contains such a cluster. The
      homoaconitases of A. nidulans and S. cerevisiae share only 20% sequence identity
      with S. cerevisiae aconitase. The pH optimum for the activity of A. nidulans
      homoaconitase in 0.1 M potassium phosphate buffer is between pH 8.1 and pH 8.6.
      Homoaconitase exhibited an apparent K(m) of 1.1 mM toward homoisocitric acid. The
      specific activity of homoaconitase was reduced by up to six-fold in mycelia grown
      in the presence of L-lysine, suggesting that it is regulated by lysine.

PMID- 9268015
TI  - The IBP genes of maize are expressed in non-meristematic, elongating cells of the
      seedling and in abortive floral organs.
AB  - The transcription start site of the maize Shrunken-1 (Sh-1) gene is sufficient
      for transcriptional initiation in the absence of other promoter elements and is
      recognized in vitro by the Initiator Binding Protein (IBP). We describe here in
      situ hybridization experiments performed on various maize tissues to quantify IBP
      transcription at the cellular level. IBP transcripts are found in the endosperm
      and in differentiating, enlarging cells of the shoot and the root of the maize
      seedling. This expression pattern overlaps with that of the Sh-1 gene and is
      therefore compatible with the hypothesis that the Sh-1 transcription start site
      is a target for IBP. In the developing spikelets of male and female
      inflorescences IBP transcript levels are very high in those organs that are later
      aborted when flowers become unisexual. Overexpression of the maize IBP1 gene
      product in transgenic tobacco causes a reduction in internodal elongation and
      effects gibberellin hormonal balance. The cellular expression pattern described
      here establishes IBP transcripts as an interesting molecular marker for
      enlarging, and presumably differentiating, cells released from the root or shoot
      apex.

PMID- 9268016
TI  - Enzymatic responses of Drosophila melanogaster to long- and short-term exposures
      to ethanol.
AB  - The effects of environmental ethanol on larva-to-pupa survival and on the
      activities of four enzymes were investigated in three Drosophila melanogaster
      strains. The strains had different allelic combinations at the Odh and Aldox loci
      on their third chromosomes, but they all carried the Adh(S)-Gpdh(F) allelic
      combination on the second chromosome. Replicates of each of the strains were
      exposed to three different ethanol treatments: (i) no ethanol in the medium
      (control); (ii) 5% ethanol for a single generation (short-term exposure); (iii)
      5% ethanol for 20 generations (long-term exposure). In all experiments, the
      activities of four enzymes (ADH, ODH, GPDH and AOX) were measured in larvae,
      pupae and adults. The results showed that (i) the larval and adult metabolic
      responses to environmental ethanol were different; (ii) enzyme activity changes
      under short-term exposure differed from those measured under long-term exposure;
      (iii) the activities of the allozymes common to all strains (ADH-S and GPDH-F),
      differed depending on the genetic background. Changes in larva-to-pupa survival
      were seen when the larvae of control and exposed lines of the three strains were
      confronted with various concentrations of ethanol. In all three strains, the
      exposed lines had significantly higher initial survival rate and ethanol
      tolerance than the control lines. Strain-specific differences were observed in
      the ethanol tolerance of both types of line.

PMID- 9268017
TI  - A tripartite group II intron in mitochondria of an angiosperm plant.
AB  - In mitochondria of flowering plants the nad5 open reading frame is assembled from
      five exons via two conventional cis-splicing and two trans-splicing events. Trans
      splicing between exons c and d in wheat, petunia and Arabidopsis involves a
      bipartite group II intron structure, while in Oenothera a large portion of intron
      domains I-IV is missing from the major genomic locus. This intron region has been
      lost downstream of exon c and is now found in a distant genomic region.
      Intragenomic recombination across an 11 nucleotide sequence has separated these
      intron parts, which now have to be reassembled from three independent RNA
      precursors. This organisation coexists with highly substoichiometric copy numbers
      of the bipartite intron arrangement, consistent with an evolutionary origin of
      the tripartite intron by genomic disruption.

PMID- 9268018
TI  - Double-strand breaks increase the incidence of genetic deletion associated with
      intermolecular recombination in bacteriophage T7.
AB  - An in vitro DNA replication system based on extracts prepared from Escherichia
      coli cells infected with bacteriophage T7 was used to study deletion associated
      with the repair of double-strand breaks. The gene for T7 ligase was interrupted
      by a DNA insert which included 17-bp direct repeats. Deletion between the repeats
      restored the reading frame of the gene, and these DNA molecules could be detected
      by their ability to give rise to ligase-positive phage after in vitro packaging.
      T7 genomes that had a pre-existing double-strand break located between the direct
      repeats were incubated together with intact genomes which had the same direct
      repeats. Genetic markers placed on either side of the insert in the ligase gene
      allowed identification of the source of DNA molecules that underwent deletion
      between the direct repeats. This allowed an assessment of the participation of
      the molecules with strand breaks in the deletion process, under conditions where
      any mechanism could contribute to deletion. Approximately three-quarters of the
      T7 molecules that had lost the region between the direct repeats contained one or
      both of the partial genomes originally introduced into the reactions. About 50%
      of the genomes which had undergone deletion had recombined markers between the
      partial and intact genomes. The data demonstrate that double-strand breaks
      substantially enhance the contribution of intermolecular recombination to
      deletion.

PMID- 9268019
TI  - Transcriptional regulation of pilC2 in Neisseria gonorrhoeae: response to oxygen
      availability and evidence for growth-phase regulation in Escherichia coli.
AB  - The type-4 pilus of Neisseria gonorrhoeae is a dominant surface antigen which
      facilitates adhesion to host target cells, an essential event in gonococcal
      infection. pilC2 encodes a 110-kDa protein involved in pilus assembly, pilus
      mediated adherence to human epithelial cells in culture and natural competence
      for DNA transformation. Luciferase activity directed from a chromosomal
      pilC2::luxAB transcriptional fusion was reduced approximately 4-fold when cells
      were grown anaerobically. We observed a concomitant reduction in gonococcal
      piliation by electron microscopy and a reduction in the ability to adhere to ME
      180 human epithelial cells when bacteria were grown in the absence of oxygen.
      Furthermore, we present evidence for growth-phase regulation of the gonococcal
      pilC2 gene in Escherichia coli, and show that all sequences necessary for growth
      phase regulation are contained on a 121-bp pilC2 fragment. Expression from the
      minimal pilC2 fragment fused to lacZ in single-copy in E. coli was induced 2-fold
      when cells entered stationary phase. Surprisingly, induction does not require
      rpoS, the gene, which encodes the starvation-induced sigma factor RpoS. In
      summary, we have demonstrated that pilC2 is both positively and negatively
      regulated at the level of transcription. This regulation is most probably
      relevant to physiological conditions within the human host which influence
      gonococcal infections.

PMID- 9268020
TI  - Cytosine methylation and nucleolar dominance in cereal hybrids.
AB  - In wheat-rye hybrids the nucleolus organizer regions (NORs), the sites of
      ribosomal RNA genes, from rye are suppressed. Wheat and wheat-rye hybrid genetic
      stocks containing different numbers of wheat and rye nucleolus organizers, as
      well as addition lines and rye-barley hybrids, were used in Southern
      hybridization experiments to determine the cause of nucleolar dominance and
      suppression in cereal hybrids. Based on the use of restriction endonucleases that
      cleave near the ends of the spacer unit and an additional, methylation-sensitive
      enzyme, HpaII, which does not recognize the CCGG restriction site if the internal
      C is methylated, an indirect method of assaying NOR expression was established.
      The results indicated that cleavage by the HpaII enzyme of the rye NOR sequences,
      is reduced when major NORs from other cereals were present. The reduction in the
      number of rye rRNA genes containing an unmethylated CCGG site in the promoter was
      associated with the suppression of the rye nucleolus. These results are
      consistent with a model in which promoter and upstream regulatory repeats of
      ribosomal RNA genes compete for limited concentrations of regulatory proteins,
      and genes that are methylated at key binding sites fail to engage these
      regulatory proteins and thus remain inactive.

PMID- 9268021
TI  - AtUBP3 and AtUBP4 are two closely related Arabidopsis thaliana ubiquitin-specific
      proteases present in the nucleus.
AB  - The ubiquitin-specific proteases (UBPs) are a class of enzymes vital to the
      ubiquitin pathway. These enzymes cleave ubiquitin at its C-terminus from two
      types of substrates containing (i) ubiquitin in an alpha-amino linkage, as found
      in the primary ubiquitin translation products, polyubiquitin and ubiquitin
      ribosomal fusion proteins, or (ii) ubiquitin in an epsilon-amino linkage, as
      found in multiubiquitin chains either unattached or conjugated to cellular
      proteins. We have isolated cDNAs for two Arabidopsis thaliana genes, AtUBP3 and
      AtUBP4, which encode UBPs that are 93% identical. These two cDNAs represent the
      only two members of this subgroup and encode the smallest UBPs described to date
      in any organism. Using in vivo assays in Escherichia coli that allow the
      coexpression of a UBP with a putative substrate, we have shown that AtUBP3 and
      AtUBP4 can specifically deubiquitinate the artificial substrate Ub-X-beta-gal but
      cannot act upon the natural alpha-amino-linked ubiquitin fusions Arabidopsis Ub
      CEP52 and Arabidopsis polyubiquitin. Affinity-purified antibody prepared against
      AtUBP3 expressed in E. coli recognizes both AtUBP3 and AtUBP4. AtUBP3 and/or
      AtUBP4 are present in all Arabidopsis organs examined and at multiple
      developmental stages. Subcellular localization studies show that AtUBP3 and/or
      AtUBP4 are present in nuclear extracts. Possible physiological roles for these
      UBPs are discussed.

PMID- 9268022
TI  - Homology of AFLP products in three mapping populations of barley.
AB  - Segregation of 850 polymorphic AFLP (amplified fragment length polymorphism)
      fragments was followed in three different doubled haploid (DH) barley
      populations, Dicktoo x Morex (DM), Igri x Franka (IF) and Blenheim x E224/3 (BE),
      which had previously been used to construct linkage maps using other molecular
      markers. The final maps consisted of 310, 655 and 474 markers, of which 234, 194
      and 376, respectively, were AFLPs. A comparison of profiles from the parental
      lines identified 51 similar-sized AFLPs segregating in both DM and IF
      populations, 20 in the DM and BE populations and 18 in the IF and BE populations.
      Eight segregated in all three. Analysis of the complete datasets for each of the
      populations using Joinmap V.2. indicated that in general terms each of the AFLPs
      which were polymorphic in more than one population mapped to the same genetic
      locus. The number of co-dominant markers segregating in a single population
      ranged from 6% for DM to 12.6% for IF. These results are discussed in the context
      of using AFLP in genetic linkage and diversity studies.

PMID- 9268023
TI  - Heat stress transcription factors from tomato can functionally replace HSF1 in
      the yeast Saccharomyces cerevisiae.
AB  - The fact that yeast HSF1 is essential for survival under nonstress conditions can
      be used to test heterologous Hsfs for the ability to substitute for the
      endogenous protein. Our results demonstrate that like Hsf of Drosophila, tomato
      Hsfs A1 and A2 can functionally replace the corresponding yeast protein, but Hsf
      B1 cannot. In addition to survival at 28 degrees C, we checked the transformed
      yeast strains for temperature sensitivity of growth, induced thermotolerance and
      activator function using two different lacZ reporter constructs. Tests with full
      length Hsfs were supplemented by assays using mutant Hsfs lacking parts of their
      C-terminal activator region or oligomerization domain, or containing amino acid
      substitutions in the DNA-binding domain. Remarkably, results with the yeast
      system are basically similar to those obtained by the analysis of the same Hsfs
      as transcriptional activators in a tobacco protoplast assay. Most surprising is
      the failure of HsfB1 to substitute for the yeast Hsf. The defect can be overcome
      by addition to HsfB1 of a short C-terminal peptide motif from HsfA2 (34 amino
      acid residues), which represents a type of minimal activator necessary for
      interaction with the yeast transcription apparatus. Deletion of the
      oligomerization domain (HR-A/B) does not interfere with Hsf function for survival
      or growth at higher temperatures. But monomeric Hsf has a markedly reduced
      affinity for DNA, as shown by lacZ reporter and band-shift assays.

PMID- 9268024
TI  - Characterisation of the Schizosaccharomyces pombe rad4/cut5 mutant phenotypes:
      dissection of DNA replication and G2 checkpoint control function.
AB  - Mutation of the essential Schizosaccharomyces pombe rad4/cut5 gene causes
      sensitivity to UV and ionising radiation at the permissive temperature whilst at
      the restrictive temperature cells fail to undergo DNA replication but still
      attempt mitosis owing to a defective S-phase checkpoint response. Many mutations
      in genes encoding DNA replication proteins also abolish checkpoint responses,
      possibly because the replication machinery is a pre-requisite for the generation
      of the signal. We demonstrate here that rad4/cut5 cells fail to arrest cell
      division when treated with the replication inhibitor hydroxyurea at the semi
      permissive temperature 32 degrees C, but retain essentially normal replicative
      capacity. This demonstrates that the replication and checkpoint function of the
      rad4/cut5 gene product can be separated and that the Rad4 protein differs from
      other replication proteins in being directly involved in generating the S-phase
      checkpoint signal. Furthermore, we have investigated the checkpoint response or
      rad4/cut5-deficient cells to gamma-irradiation and UV-mimetic drugs. We find
      that, at the restrictive temperature, the rad4-/cut5- cells fail to delay mitosis
      in response to gamma-irradiation whilst retaining a normal checkpoint response to
      the UV-mimetic drug 4-nitroquinoline-1-oxide. The lack of the gamma-irradiation
      checkpoint is reminiscent of the deficiency associated with mutation of the human
      ATM locus, the causative deficiency of the heritable disorder ataxia
      telangiectasia. The implications of our results for the organisation of distinct
      checkpoint-response pathways in both fission yeast and mammalian cells are
      discussed. Moreover the data are consistent with a model in which the generation
      of the S-Phase checkpoint signal is DNA polymerase epsilon dependent.

PMID- 9268025
TI  - Cloning and characterization of the lipoyl-protein ligase gene LIPB from the
      yeast Kluyveromyces lactis: synergistic respiratory deficiency due to mutations
      in LIPB and mitochondrial F1-ATPase subunits.
AB  - The mgi1-4 and mgi2-1 mutants of the petite-negative yeast Kluyveromyces lactis
      have mutations in the beta- and alpha-subunits of the mitochondrial F1-ATPase,
      respectively. The mutants are respiratory competent but can form petites with
      deletions in mitochondrial DNA. In this study a cryptic nuclear mutation (lipB-1)
      was identified which, in combination with the mgi alleles, displays a synergistic
      respiratory-deficient phenotype on glycerol medium. The gene defined by the
      mutation was cloned and shown to encode a polypeptide of 332 amino acids with an
      N-terminal sequence characteristic of a mitochondrial targeting signal. The
      deduced protein shares 27% sequence identity with the product of the Escherichia
      coli lipB gene, which encodes a lipoyl-protein ligase involved in the attachment
      of lipoyl groups to lipoate-dependent apoproteins. A K. lactis strain carrying a
      disrupted lipB allele is severely compromised for growth on glycerol medium. The
      growth defect cannot be rescued by addition of lipoic acid, but cell growth can
      be restored on medium containing ethanol plus succinate. In addition, it was
      observed that lipB mutants of K. lactis, unlike the wild-type, are unable to
      utilize glycine as sole nitrogen source, indicating that activity of the glycine
      decarboxylase complex (GDC) is also affected. Taken together, these findings
      suggest that LIPB is the main determinant of the lipoyl-protein ligase activity
      required for lipoylation of enzymes such as alpha-ketoacid dehydrogenases and
      GDC.

PMID- 9268036
TI  - Mutagenicity of cyclopenta-fused polynuclear aromatic hydrocarbons and a non
      polar fraction from a fuel combustion sample in a Salmonella forward mutation
      assay without exogenous metabolic activation.
AB  - A series of cyclopenta-fused polynuclear aromatic hydrocarbons (PAH) were tested
      for mutagenicity in a bacterial forward mutation assay based on resistance to 8
      azaguanine (8-AG) in Salmonella typhimurium TM677 in the absence of Aroclor
      induced rat liver postmitochondrial supernatant (PMS). All of the aceanthrylenes
      tested were mutagenic in the absence of PMS, whereas none of the
      acephenanthrylenes were active. The following mutagenic potency series expressed
      as the minimum detectable mutagen concentration (MDMC) in nmol/ml was obtained:
      aceanthrylene (AA) (5.5); cyclopent[h,i]aceanthrylene (CPAA)(18.2); 6
      methylaceanthrylene (6-MeAA)(112); 1,2,6,7-tetrahydrocyclopent[h,i]aceanthrylene
      (THCPAA) (166); 1,2-dihydroaceanthrylene (DHAA) (298). Saturation of the
      cyclopenta rings or methylation at the 6-position of AA reduced, but did not
      eliminate, mutagenicity measured in the absence of PMS. AA was unusual because it
      was approximately 4-fold more mutagenic in the absence of PMS than in its
      presence. The other aceanthrylenes tested were 1.3-10.7 times more mutagenic in
      the presence of PMS than in its absence to give an MDMC potency series of: CPAA
      (3.8); 6-MeAA (10.5); AA (19.9); THCPAA (52.9); DHAA (229). Approximately 20% of
      the PMS-independent mutagenicity in a combustion sample from ethylene burned
      under fuel-rich conditions was found in a fraction containing only non-polar, 4-7
      ring PAHs, widely attributed to be mutagenic only in the presence of PMS. None of
      this mutagenicity could be attributed to aceanthrylenes, thus other non-polar
      PAHs appear to possess significant PMS-independent mutagenicity as well.

PMID- 9268037
TI  - Pharmacokinetic parameters of genotoxic activity inferred from the comparison of
      the kinetics of MN-PCE induced by chemical agents and ionizing radiation.
AB  - Some kinetic parameters of clastogenic activity of cyclophosphamide were inferred
      by means of the comparison of its kinetics of micronucleated polychromatic
      erythrocytes (MN-PCE) formation with the kinetics induced by radiation. The same
      reasoning was also applied to the kinetics obtained by treatment with mitomycin C
      (MMC), arabinocyl cytosine (Ara-C) and 6-mercaptopurine (6-MOP), based on
      previously reported data from the literature. The results indicate that the
      latency period (LP) and half-lives (HL) vary from one mutagen to another. For
      MMC, they are very similar to radiation indicating a rapid distribution and
      reaction. CP presents very long LP and HL which agree with the requirement of
      mutagen activation. Ara-C showed a very short LP which suggests a rapid
      activation and fast induction of damage in DNA. 6-MOP presented a very long LP
      which agreed with the requirement of its incorporation into DNA to cause
      micronucleus (MN). From the data obtained in the present work, it can be
      concluded that the comparison of the kinetics of MN-PCE formation induced by
      chemical agents with that obtained by the exposure to an acute dose of radiation
      permits one to estimate some parameters of the kinetics of clastogenic activity
      of chemical agents, like the LP and the HL. This seems to be valid for agents
      that act through the induction of DNA lesions; in the case of agents whose
      clastogenic activity is through other mechanisms, such as the inhibition or
      alteration of the process of duplication of the DNA, the kinetic parameters are
      not equivalent to the LP and HL; however, they could provide information on their
      possible mechanism of action.

PMID- 9268038
TI  - In vitro induction of micronuclei in lymphocytes: the use of bromodeoxyuridine as
      a proliferation marker.
AB  - A simple method to determine the induction of micronuclei in cultured lymphocytes
      is described as an alternative to the cytochalasin-B method. It is proposed for
      use in the evaluation of the genotoxic potential of agents in vitro. It allows
      the recording of events only in the proliferating population of cells and at the
      same time it eliminates the possibility of recording combined effects with a
      cytokinesis-blocking agent. 16 microM bromodeoxyuridine (BrdU) was used to label
      proliferating cells that were treated with colcemid or mitomycin C at different
      concentrations. A monoclonal antibody against BrdU incorporated in the DNA and a
      peroxidase-diaminobenzidine brown stain were used to identify those cycling cells
      in a slide. To obtain the maximum yield of micronuclei, the best time for the
      addition of bromodeoxyuridine was found to be at 40 h from the initiation of
      cultures, 8 h before treating cells with the chemicals. Identification of
      micronuclei was easy, fast and unequivocal. In addition, the formation of
      structures similar to micronuclei, but that still are part of the nucleus could
      be observed. It is not clear if these structures are an intermediate stage in the
      formation of MN, but this methodology provides the possibility of observing and
      studying them.

PMID- 9268039
TI  - Metabolic activation of meta-phenylenediamine by the alga Chlamydomonas
      reinhardtii.
AB  - Promutagens/procarcinogens arylamines are widely distributed in the environment.
      While it is accepted that these compounds can be metabolized to ultimate mutagens
      in mammals and higher plants, in aquatic plants they have not yet been explored.
      Intact wild-type and repair-deficient strains of Chlamydomonas reinhardtii and
      Saccharomyces cerevisiae D7 strain were assayed for their ability to activate
      meta-phenylenediamine (m-PDA) to an ultimate mutagen. The different responses of
      the algal wild-type strain and repair-deficient strains to the toxic and
      mutagenic effects of m-PDA were observed. Recombination repair played an
      important role in repair of damage induced to C. reinhardtii DNA by this
      arylamine. The examined isomer of phenylenediamine induced mutations in both
      algal and yeast cells. m-PDA was activated in the algal cell/microbe coincubation
      assay in which algal cells were used as an activating system and bacteria
      Salmonella typhimurium and yeast Saccharomyces cerevisiae as the genetic
      indicator organisms. This new assay is, in addition to the animal microsome
      metabolizing system and the plant cell/microbe coincubation assay, suitable for
      the detection of environmental promutagens and their conversion to mutagens
      mainly in aquatic environments.

PMID- 9268041
TI  - 2-Nitropropane-induced DNA damage in rat bone marrow.
AB  - DNA damage detected by the comet assay (single cell gel electrophoresis) and 8
      oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation in DNA in the bone marrow
      has been studied in groups of 6 male Wistar rats treated with a single i.p.
      injection of the carcinogen 2-nitropropane (2-NP, 100 mg/kg body weight) or
      vehicle. Twenty-four hours after 2-NP the average tail length in the comet assay
      in bone marrow cells was increased from 1.46 +/- 0.27 to 9.61 +/- 1.56 microm
      (mean /- SD, p < 0.01), and 8-oxodG levels in the DNA were increased from 1.04 +/
      0.50 to 5.14 +/- 2.42 per 10(5) dG (p < 0.01). There was a close correlation
      between the comet tail length and the 8-oxodG level (r = 0.89, p < 0.05). The
      results indicate that 2-NP inflicts DNA damage in the bone marrow cells and thus
      could be leukemogenic.

PMID- 9268040
TI  - Assessment of the in vivo mutagenicity of ethylene oxide in the tissues of B6C3F1
      lacI transgenic mice following inhalation exposure.
AB  - In the present study, the lacI mutant frequency was determined in the tissues of
      B6C3F1 lacI transgenic mice exposed by inhalation to ethylene oxide (EO). Groups
      of 15 male transgenic lacI B6C3F1 mice were exposed to either 0, 50, 100, or 200
      ppm EO for 4 weeks (6 h/day, 5 days/week) and were sacrificed at 0, 2, or 8 weeks
      after the last EO exposure. The lacI transgene was recovered from lung, bone
      marrow, spleen, and germ cells for determination of the lacI mutant frequency.
      The tissues selected for analysis were tumor target site tissues in chronic
      bioassays (lung tumors and lymphomas) and germ cells. The lacI mutant frequency
      in lung was significantly increased at 8 weeks post exposure to 200 ppm EO (6.2
      +/- 2.2 vs. 9.1 +/- 1.5. p = 0.046). In contrast, the lacI mutant frequency in
      spleen and bone marrow at 2 and 8 weeks was not significantly increased in mice
      exposed to 200 ppm EO. The lacI mutant frequencies in male germ cells for 200 ppm
      EO-exposed mice were not increased compared to air controls at 2 and 8 weeks post
      exposure. In a spleen cell fraction two of three EO-exposed mice at the 200 ppm
      exposure level demonstrated an elevated lacI mutant frequency. The increased lacI
      mutant frequency in these animals was likely due to mutant siblings that
      contained background G:C --> A:T transitions at CpG sites. These results
      demonstrate that a 4-week inhalation exposure to EO is mutagenic in lung.
      However, EO did not increase the frequency of mutations recovered at the lacI
      transgene in other tissues examined under the conditions used in the present
      studies. Since the mutational spectrum for EO in other systems consists of an
      increased proportion of large deletions, the lack of a mutagenic response in the
      tissues examined is likely due to the lack of recovery of large deletions in
      lambda-based shuttle vector systems. These data indicate that a primary mechanism
      of EO-induced mutagenicity in vivo is likely through the induction of deletions,
      not specific point mutations.

PMID- 9268043
TI  - Evaluation of the genotoxicity of municipal sewage effluent using the marine worm
      Platynereis dumerilii (Polychaeta: Nereidae).
AB  - Samples of settled (primary) effluent were collected from a municipal sewage
      treatment works at Newton Abbot, Devon, UK, a site which discharges primary
      effluent via long sea pipeline into the English Channel (minimum of 200-fold
      initial dilution). Sewage samples were collected during the period February-April
      1995 and were analysed for standard physico-chemical parameters (ammonia,
      chemical oxygen demand, conductivity, non-purgeable organic carbon and settled
      solids). Samples were also tested for cytotoxicity, genotoxicity, and for
      developmental effects in the embryo-larval stages of the marine worm, Platynereis
      dumerilii. Exposure to sewage concentrations of > or = 10% (v/v) in seawater at
      20 +/- 1 degrees C led to a marked reduction in normal embryo-larval development
      (7 h EC50 values from 10% to 18% v/v, n = 5). There was also evidence of a
      simultaneous delay in the cell cycle progression (as determined by sister
      chromatid differential staining) following embryo-larval exposures to sewage
      concentrations of > or = 10% (v/v). Following the calculation of the Maximum
      Tolerated Dose (MTD), based on cytotoxic and developmental effects, cells from
      the same embryo-larvae were analysed for chromosomal aberrations (CAs). Results
      were consistent for all samples tested, demonstrating the absence of cytogenetic
      damage following the in vivo exposure of polychaete embryo-larvae to settled
      sewage.

PMID- 9268042
TI  - Trigonelline, a naturally occurring constituent of green coffee beans behind the
      mutagenic activity of roasted coffee?
AB  - Trigonelline and amino acids are natural components in green coffee beans. Model
      systems mimicking coffee roasting were used to produce heated samples of
      trigonelline, amino acids and glucose. Trigonelline and amino acids were heated
      separately or in combinations for 20 min at 250 degrees C. The results of
      bacteria mutation assays (Salmonella typhimurium strains TA 98, YG 1024 and YG
      1029) showed that trigonelline, alone or in combination with most of the single
      amino acids and mixtures of amino acids, yielded potent mutagenic activity. Of
      the singly heated compounds, the highest mutagenic activity was found for
      trigonelline. The mutagenic activity detected with metabolic activation of the
      heated trigonelline samples indicated that the mutagenic compounds might be
      amines; however, higher mutagenic activity was found for trigonelline and its
      combinations without metabolic activation, which suggests that other types of
      mutagens (direct-acting) were predominant. High-performance liquid
      chromatographic analysis of some of the heated samples did not reveal the
      presence of any known mutagenic heterocyclic amine.

PMID- 9268044
TI  - Cytogenetic effects of X-rays in the guinea pig female germ cells. I. The
      immature oocyte.
AB  - In female mammals, the immature oocyte is the germ cell most at risk, from the
      genetic point of view. We have previously shown that ovaries of newborn guinea
      pigs contain a great majority of immature oocytes and small numbers of maturing
      oocytes. At this time, all immature oocytes are in a typical diplotene stage,
      comparable to that of the human resting oocyte. Furthermore, the LD50 of the
      guinea pig oocytes is about 4 Gy, like that of human oocytes. Consequently,
      performing genetic studies on guinea pig oocytes irradiated just after birth
      constitutes a very useful approach to predict the mutational response of the
      human resting oocyte. Female guinea pigs were X-irradiated with 1 or 2 Gy within
      24 h of birth, and their meiotically competent oocytes were collected and
      cultured to the metaphase I stage, 1 year after treatment, ensuring that all
      oocytes were at the immature stage at the time of irradiation. The proportion of
      oocytes that showed chromosome aberrations (breaks, fragments or interchanges)
      was only 1-2% Gy(-1). Although not definitive, these results provide support for
      a low risk in women from an exposure of the immature oocyte to low doses of
      radiation.

PMID- 9268045
TI  - Cytogenetic effects of X-rays in the guinea pig female germ cells. II. The
      maturing oocyte.
AB  - In a previous study, we showed that the guinea pig constitutes one of the best
      models to evaluate the genetic risk associated with an irradiation of the human
      female germ cells. Herewith, experiments were undertaken to evaluate the
      chromosomal radiosensitivity of oocytes of this species at two different stages
      of follicular development, separated by only 1 week. Female guinea pigs were X
      irradiated on the ovaries, at either the beginning (day 3) or the middle (day 10)
      of the 17-day oestrous cycle. The doses delivered were 1 or 2 Gy. Meiotically
      competent oocytes were collected 1 week after irradiation (day 3) or immediately
      thereafter (day 10), and they were cultured to the metaphase of the first meiosis
      (MI) and examined for the presence of chromosome aberrations. Our data
      demonstrated a dramatic increase in the radiosensitivity of the oocyte during
      this short time interval: oocytes irradiated at the beginning of the oestrous
      cycle had a low frequency of chromosome aberrations, while those irradiated at
      the middle of the oestrous cycle (when growing Graafian follicles are clearly
      visible at the surface of the ovaries) exhibited heavy chromosome damage.
      However, we also found that oocytes irradiated at the middle of the oestrous
      cycle were eliminated from the ovaries in a few days, after their evolution to
      the MII stage. The stimulation of the first meiotic division by radiation
      required less than 24 h after doses of 1 or 2 Gy and was probably due to a rapid
      atresia of the large follicles containing the oocytes. On the basis of these
      results, it can be concluded that the radiosensitivity of the nearly mature
      guinea pig oocyte (1 week before ovulation) is clearly much higher than that of
      the corresponding stage in the mouse, both in terms of sensitivity to killing and
      to induction of chromosome aberrations.

PMID- 9268046
TI  - Detection of rodent liver carcinogen genotoxicity by the alkaline single-cell gel
      electrophoresis (Comet) assay in multiple mouse organs (liver, lung, spleen,
      kidney, and bone marrow).
AB  - We have recently designed a simple method for applying the alkaline single-cell
      gel electrophoresis (SCG) assay to mouse organs. With this method, each organ is
      minced, suspended in chilled homogenizing buffer containing NaCl and Na2EDTA,
      gently homogenized using a Potter-type homogenizer set in ice, and then
      centrifuged nuclei are used for the alkaline SCG assay. In the present study, we
      used the method to assess the genotoxicity of 8 rodent hepatic carcinogens in 5
      mouse organs (liver, lung, kidney, spleen, and bone marrow). The carcinogens we
      studied were p-aminoazobenzene, auramine, 2,4-diaminotoluene, p-dichlorobenzene,
      ethylene thiourea (ETU), styrene-7,8-oxide, phenobarbital sodium, and benzene
      1,2,3,4,5,6-hexachloride (BHC); except for p-aminoazobenzene, they do not induce
      micronuclei in mouse bone marrow cells. Mice were sacrificed 3 and 24 h after the
      administration of each carcinogen. p-Aminoazobenzene, ETU, and styrene-7,8-oxide
      induced alkaline labile DNA lesions in all of the organs studied. Auramine, 2,4
      diaminotoluene, p-dichlorobenzene, and phenobarbital sodium also produced
      lesions, but their effect was greatest in the liver. BHC, which is not genotoxic
      in in vitro tests, did not show any effects. We suggest that it may be possible
      to use the alkaline SCG assay to detect in vivo activity of chemicals whose
      genotoxicity is not expressed in bone marrow cells.

PMID- 9268047
TI  - Simple detection of chemical mutagens by the alkaline single-cell gel
      electrophoresis (Comet) assay in multiple mouse organs (liver, lung, spleen,
      kidney, and bone marrow).
AB  - Recently, we designed a fast and simple method to obtain nuclei for the alkaline
      SCG assay and we tested it with mouse liver, lung, kidney, spleen, and bone
      marrow. Instead of isolating organ cells by trypsinization, we homogenized tissue
      and isolated the nuclei. Each organ was minced, and the mince was suspended in
      chilled homogenizing buffer containing NaCl and Na2EDTA, homogenized gently using
      a Potter-type homogenizer set in ice, and then centrifuged. The nuclei from the
      precipitate were used for the assay. To evaluate the validity of this method, we
      tested the genotoxicity in mouse organs of 11 chemical mutagens with different
      modes of action. Mice were sacrificed 3 and 24 h after administration of each
      mutagen. Treatment with three alkylating agents (MMS, EMS, and MNNG), a DNA
      crosslinking agent (MMC), two aromatic amines (2-AAF and phenacetin), a
      polycyclic aromatic hydrocarbon (B[a]P), and two inorganic chemicals (KBrO3 and
      K2CrO4) increased migration of the DNA from mouse organs. 5-FU (a base analog)
      and colchicine (a spindle poison) treatment produced negative results in all
      organ studied. Considering that the alkaline SCG assay detects genotoxicity as
      DNA fragments derived from DNA single-strand breaks and alkali-labile damage, our
      results showed that the SCG assay using our homogenization technique detected
      chemical mutagens as a function of their modes of action.

PMID- 9268048
TI  - Somatic and germ cell effects in rats and mice after treatment with 1,3-butadiene
      and its metabolites, 1,2-epoxybutene and 1,2,3,4-diepoxybutane.
AB  - 1,3-Butadiene is produced in large quantities for use in the manufacture of
      synthetic rubber. It is also an environmental pollutant. There is concern about
      exposure to 1,3-butadiene as it has been shown to produce tumours in rats, mice
      and an increased risk of leukaemia in humans. It has also been shown to produce
      germ cell effects in mice. Differences in responses to 1,3-butadiene have been
      reported in rats and mice, possibly due to different metabolic capabilities. The
      present study thus investigated somatic and germ cell effects of 1,3-butadiene in
      mice and its metabolites in both rats and mice to help determine species
      differences using different endpoints for genotoxic effects. These included DNA
      strand breakage as measured in the single cell gel electrophoresis (Comet assay)
      in bone marrow and testicular cells, and micronuclei in bone marrow cells using
      both the acridine orange and Giemsa staining methods. Unscheduled DNA synthesis
      (UDS) was also measured in the testes of mice. CD-1 mice were exposed to 1,3
      butadiene by inhalation for 6 h/day for 4 weeks, and CD-1 mice and Sprague-Dawley
      rats to the metabolites after i.p. injection. 1,3-Butadiene did not affect liver,
      bone marrow and testicular cells in mice as measured in the Comet assay. After
      treatment with 1,2-epoxybutene in the Comet assay, there was a response in the
      testes in mice but not in rats and there was little or no effect in the bone
      marrow assay in mice but there was in rats. After treatment with 1,2,3,4
      diepoxybutane in the Comet assay in mice, there was a response in the bone marrow
      cells but not in the testicular cells, and in rats there was also a response only
      in bone marrow cells. There was an increase in micronuclei in both rats and mice
      with both metabolites, but clastogenicity was stronger with 1,2,3,4
      diepoxybutane, occurring at lower doses, than with 1,2-epoxybutene. In the UDS
      assay in the testes of mice, there was an increase in response with 1,2,3,4
      diepoxybutane treatment but not with 1,2-epoxybutene. These studies would appear
      to confirm a species difference of CD-1 mice and Sprague-Dawley rats, where mice
      were sensitive at lower doses than rats.

PMID- 9268049
TI  - Development of a standard reference material for diesel mutagenicity in the
      Salmonella plate incorporation assay.
AB  - The present study documents the mutagenicity of a new National Institute of
      Standards and Technology (NIST) standard reference material (SRM) in the
      Salmonella plate incorporation assay. This study is in response to a previous
      recommendation by the World Health Organization to develop large batches of new
      SRMs for biological and chemical research. SRM 1975 is a dichloromethane (DCM)
      extract of 5.6 kg of filter-collected combustion particulate matter (SRM 2975)
      from operating forklifts with diesel engines. The mutagenicity and a summary of
      the related chemical analysis of mutagens in SRM 1975 is presented in this paper,
      and are available from the NIST. Mutagenicity test conditions were: Salmonella
      typhimurium TA98, TA100 (standard strains); TA98NR, TA100NR (nitroreductase (NR)
      gene deficient); and YG1021 and YG1026 (NR gene addition); 10 dose levels in the
      linear portion of the dose-response curve; duplicate plates per dose; and S9 at
      6.4% or 1.1 mg of protein/plate. Four rounds of testing were conducted. Rounds
      were conducted at least 1 week apart. Slopes (revertants/microg) were calculated
      by the linear regression rejection model of Bernstein and by the Stead and
      Krewski models which analyze non-linear data. The GeneTox Manager software
      package developed at the EPA was used to record the data and calculate the
      slopes. Results demonstrated: (1) the ranking of slopes without S9 was: YG1021 >
      TA98 > TA98NR > YG1026 > TA100 > TA100NR in all three statistical models; (2) the
      mutagenic activity of SRM 1975 was significantly increased by the presence of the
      NR gene; (3) the slope values for the TA100 series were significantly less than
      for the TA98 series; (4) in general, the addition of the S9 significantly reduced
      mutagenic activity; (5) the mutagenic activity of the SRM 1975 was stable over
      time and variability was low (generally less than 20% in slope values over the 4
      rounds); and (6) agreement of the slope values among the three models was
      excellent due to the linear nature of the data. These data will be useful in
      ranking other diesel and air samples for mutagenic activity, for quality
      assurance of data generated in different laboratories, for quality control within
      a laboratory, and as positive control values for future air and automotive
      emission studies.

PMID- 9268050
TI  - The bimC family of kinesins: essential bipolar mitotic motors driving centrosome
      separation.

PMID- 9268051
TI  - Protein depletion and refeeding change the proportion of mouse liver glutathione
      S-transferase subunits.
AB  - The effect of protein depletion followed by refeeding with a normal diet on the
      content of mouse liver cytosolic proteins was studied. By peptide-mass
      fingerprinting and N-terminal sequencing, three polypeptides whose contents
      changed with dietary protein level were identified as glutathione S-transferases
      (GST) Yb1, Yc and Yf subunits. Five days of depletion caused the increase of Yb1
      and Yf (21.6% and 78.5%, respectively) and the decrease of Yc (31.2%). After two
      days of refeeding, Yb1 and Yc were practically restored, while the neoplastic
      marker Yf remained higher (63.4%). None of the nutritional conditions tested
      induced new GSTs. While protein depletion-refeeding altered the ratios between
      the constitutive GST subunits, total liver GST content and activity were
      unaffected by depletion and slightly increased by refeeding. The increased
      amounts of Yb1 and Yf, and the maintenance of total GST content, indicate that
      during protein depletion, the GST subunits levels are controlled by mechanisms
      different from the majority of cytosolic proteins.

PMID- 9268053
TI  - Involvement of antizyme-like regulatory protein in polyamine-caused repression of
      ornithine decarboxylase in insect-derived Trichoplusia ni 5 cells.
AB  - Addition of spermidine to culture medium of insect cells, Trichoplusia ni 5, at a
      low cellular density suppressed ornithine decarboxylase (ODC; EC 4.1.1.17)
      activity and induced ODC inhibitory activity. The inhibitory factor was non
      dialyzable, temperature-sensitive, and could reversibly form an inactive complex
      with ODC. It showed a time-independent and non-stoichiometric pattern of
      inhibition. Upon addition of spermidine to cultured cells with preinduced ODC,
      the enzyme decayed more rapidly than after addition of cycloheximide. These data
      strongly suggested that ODC of Tn5 cells is under negative feedback control by
      polyamines, in which an antizyme-like regulatory protein plays an essential role.

PMID- 9268052
TI  - Effect of extremely low frequency (ELF) magnetic field exposure on morphological
      and biophysical properties of human lymphoid cell line (Raji).
AB  - Human B lymphoid cells (Raji) were exposed for 72 h to a 50 Hz sinusoidal
      magnetic field at a density of 2 milliTesla (rms). The results of exposure showed
      a decrease in membrane fluidity as detected by Laurdan emission spectroscopy and
      DPH fluorescence polarization. Field exposure also resulted in a reorganization
      of cytoskeletal components. Scanning electron microscopy (SEM) revealed a loss of
      microvilli in the exposed cells. This change in plasma membrane morphology was
      accompanied by a different actin distribution, as detected by phalloidin
      fluorescence. We also present evidence that EMF exposure of Raji cells can
      interfere with protein phosphorylation. Our observations confirm the hypothesis
      that electric and magnetic fields may modify the plasma membrane structure and
      interfere with the initiation of the signal cascade pathways.

PMID- 9268054
TI  - G1 accumulation caused by iron deprivation with deferoxamine does not accompany
      change of pRB status in ML-1 cells.
AB  - We analyzed G1 accumulation induced by the iron chelator deferoxamine B mesylate
      (DFO) compared it with that caused by etoposide and cytosine arabinoside (AraC).
      The results showed that p53 protein increased with all three treatments without
      an increase in p53 mRNA. After treatment for 3 or 6 h, p21 mRNA increased with
      10(-4) DFO to 159% or 556% of pretreatment levels, to 509% or 391% with 10(-5)
      etoposide, and to 263% or 304% with 10(-5) AraC. Induction of p21 protein was not
      observed with fluorescence activated cell sorting and Western blot analysis after
      treatment with DFO or AraC. Treatment with DFO did not cause any change in levels
      of CDK4 mRNA or protein, whereas etoposide or AraC treatment did diminish CDK4
      protein. Enzyme linked immunosorbent assay for pRB and its phosphorylation, which
      reflects CDK4 activity, revealed that treatment with DFO did not change the
      amount of pRB or the phosphorylation status. Results of this investigation show
      that the mechanism of G1 accumulation induced by DFO involves a p53-independent
      pathway and that expression of p21 protein may be regulated
      posttranscriptionally.

PMID- 9268055
TI  - Mechanism of beta-adrenergic agonist-induced transmural transport of glucose in
      rat small intestine. Regulation of phosphorylation of SGLT1 controls the
      function.
AB  - The perfusion of rat small intestine with 10 microM epinephrine (Epi) or 10
      microM norepinephrine resulted in significant increases in the amount of 3-O
      [methyl-3H]-D-glucose transported from the mucosal to serosal side. The Epi
      induced increases in glucose transport were coupled with selective increases in
      beta-adrenoceptor density in the mucosal membranes. Treatment with 0.1 microM
      okadaic acid increased glucose transport even in the absence of Epi, but that
      with 1 microM staurosporine or 60 microM N-[2-(methylamino)ethyl]-5-isoquinoline
      sulfonamide dihydrochloride completely inhibited the increases in glucose
      transport induced by 10 microM Epi or 10 microM dibutyryl cAMP. The maximal
      binding sites (Bmax) of [3H]phlorizin in brush border membrane (BBM) from tissues
      perfused with Epi was increased, showing increases in the binding ability of the
      Na+/glucose cotransporter (SGLT1) to glucose. Phosphorylation and
      dephosphorylation of BBM with protein kinase A (PKA) and alkaline phosphatase
      resulted in increases and decreases in Bmax of [3H]phlorizin, respectively. The
      phosphorylation state of SGLT1 immunoprecipitated from BBM incubated with [gamma
      32P]ATP-Mg2+ and PKA, and the analysis of phosphoamino acids composed of SGLT1 in
      rats given [32P]orthophosphate indicate the presence of potential sites for PKA
      mediated phosphorylation of SGLT1 at serine. These findings indicate that the
      regulation of phosphorylation of SGLT1 leads to an alteration of its function and
      results in the control of glucose transport in the rat small intestine.

PMID- 9268057
TI  - Expression of intracellular and GPI-anchored forms of GPI-specific phospholipase
      D in COS-1 cells.
AB  - Glycosylphosphatidylinositol (GPI)-specific phospholipase D (GPI-PLD) is a
      secretory protein present in high amounts in mammalian body fluids. Its cDNA has
      been isolated and encodes a signal peptide of 23 amino acids and the mature
      protein of 816 amino acids. We generated cDNAs encoding a signal peptide
      deficient and a GPI-anchored form of GPI-PLD and transiently transfected these
      constructs into COS-1 cells. The signal peptide-deficient form of GPI-PLD was
      expressed as a 90-kDa protein that was catalytically active and was localized
      intracellularly. Cells transfected with cDNA encoding the GPI-anchored form of
      GPI-PLD expressed a catalytically active enzyme of 100 kDa that could be labelled
      with [3H]ethanolamine demonstrating its modification by a GPI structure.
      Expression of the GPI-anchored form of GPI-PLD resulted in the release of
      endogenous GPI-anchored alkaline phosphatase from COS-1 cells, whereas expression
      of the intracellular form of GPI-PLD had no effect on membrane attachment of
      endogenous alkaline phosphatase. Similarly, in cells cotransfected with GPI
      anchored placental alkaline phosphatase (PLAP) and the GPI-anchored form of GPI
      PLD, PLAP was released into the cell culture supernatant while expression of the
      signal peptide-deficient form of GPI-PLD did not affect the amount of cell
      associated PLAP.

PMID- 9268056
TI  - Effect of interleukin-4 on allergen-induced arachidonic acid metabolism of rat
      peritoneal macrophages during immediate hypersensitivity reactions.
AB  - The aim of this study was to investigate the [3H]arachidonic acid metabolism of
      rat peritoneal macrophages, induced by allergen (ovalbumin) and the impact of
      interleukin-4 on this process. We established that ovalbumin induces an increase
      of [3H]arachidonic acid mobilisation from membrane lipids and of [3H]arachidonic
      acid catabolism, principally by the 5-lipoxygenase pathway, when the macrophages
      are sensitized and when serum is present. The allergen effect is not modified by
      the presence of interleukin-4 in the culture medium of macrophages 15 h before
      the allergen challenge. We also showed that, whereas the basal [3H]arachidonic
      acid metabolism of macrophages from control and actively sensitized rats is not
      different, interleukin-4 increases the [3H]arachidonic acid mobilisation and
      catabolism by cyclooxygenase and 5-lipoxygenase pathways in macrophages from
      control rats although it does not in macrophages from actively sensitized rats.
      In macrophages from control rats, the interleukin-4 effect is diminished by the
      addition of IgEs to their culture medium. In summary, interleukin-4 has an
      enhancer effect on the macrophage arachidonic acid catabolism that depends on the
      sensitization condition of the cell but that has no consequences on the further
      increased arachidonic acid metabolism induced by the allergen.

PMID- 9268058
TI  - Physiological approach to maturation of brown adipocytes in primary cell culture.
AB  - Molecular and metabolic aspects of differentiation of brown adipocytes of the
      Djungarian hamster (Phodopus sungorus) were studied in primary culture.
      Expression of uncoupling protein and lipoprotein lipase were investigated by
      Western and Northern blotting and indirect immuno-fluorescence microscopy. The
      activity of 5'-deiodinase type II was determined by a radioactive enzyme assay.
      Activity of cytochrome-c-oxidase and cell respiration rates were measured with a
      Clark electrode. We evaluated functional differences of developmental stages by
      measuring the reaction to beta-adrenergic stimulation throughout the
      differentiation process. The results show that differentiation of hamster brown
      adipocytes is an at least two-step development with physiologically discriminable
      cell types. Generation of triiodothyronine (T3) from thyroxine by activation of
      the 5'deiodinase occurs in immature brown adipocytes and is mediated primarily by
      beta1- rather than beta3-adrenergic receptors. The thermogenic capacity is
      subsequently increased in mature brown adipocytes. beta-Adrenergic receptor
      stimulation increases UCP expression of mature adipocytes but is not able to
      recruit new brown adipocytes.

PMID- 9268059
TI  - Influence of tyrosine phosphorylation on protein interaction with FcgammaRIIa.
AB  - The cytoplasmic tail of Fc(gamma)RIIa present on human neutrophils shares with
      other antigen receptors a common amino acid sequence called ITAM (Immunoreceptor
      Tyrosine-based Activation Motif). After receptor ligation, the tyrosine residues
      within this motif become phosphorylated. We prepared a recombinant fusion protein
      of the cytoplasmic tail of Fc(gamma)RIIa (containing the ITAM) with glutathione-S
      Transferase (GST-CT) to characterize the phosphorylation of Fc(gamma)RIIa and its
      ability to interact with other proteins involved in signal transduction. The GST
      CT became phosphorylated in the presence of Lyn, Hck and Syk (immunoprecipitated
      from human neutrophils), but not in the presence of Fgr. Of the active kinases,
      only Lyn (mainly present in the membrane fraction) was found to associate with
      the GST-CT in the absence of ATP. This association was also observed in
      immunoprecipitates of Fc(gamma)RIIa from resting neutrophils, suggesting that Lyn
      might be the kinase responsible for the initial Fc(gamma)RIIa phosphorylation.
      Moreover, we observed specific association of Syk and the p85 subunit of PI 3
      kinase after incubation of the GST-CT with neutrophil cytosol. This interaction
      was dependent on tyrosine phosphorylation of the GST-CT. Substitution of 269Tyr
      by Phe almost completely abolished tyrosine phosphorylation of the fusion
      protein. Substitution of either 253Tyr or 269Tyr eliminated Syk binding, but only
      253Tyr appeared to be essential for p85 binding. We hypothesize that, upon
      activation, the membrane-associated Lyn is responsible for the initial tyrosine
      phosphorylation of Fc(gamma)RIIa, thus creating a docking site for Syk and PI 3
      kinase.

PMID- 9268060
TI  - Evaluation of d-amphetamine effects on the binding of dopamine D-2 receptor
      radioligand, 18F-fallypride in nonhuman primates using positron emission
      tomography.
AB  - We have investigated the ability of dopamine to compete with the binding of the
      high affinity dopamine D2 receptor positron emission tomography (PET)
      radioligand, 18F-fallypride. In vitro dissociation of 18F-fallypride with
      dopamine in rat striatal homogenates exhibited a dissociation rate, k(off), of
      1.76 x 10(-2) min(-1) while the association rate constant, k(on), was found to be
      5.30 x 10(8) M(-1) min(-1). This resulted in a dissociation constant, K(D) of 33
      pM for 18F-fallypride. For in vivo studies, we investigated the effects of
      reserpine and d-amphetamine treatment on 18F-fallypride in an attempt to study
      competition of endogenous dopamine with the radioligand at the receptor sites in
      rats and monkeys. PET experiments with 18F-fallypride in two male rhesus monkeys
      were carried out in a PETT VI scanner. In control experiments, rapid specific
      uptake of 18F-fallypride in the striata was observed (0.05-0.06% injected dose
      (ID)/g) while nonspecifically bound tracer cleared from other parts of the brain.
      Striata/cerebellum ratios for 18F-fallypride were approximately 8 at 80 min
      postinjection, respectively. The monkeys received various doses (0.25 to 1.50
      mg/kg) of d-amphetamine (AMPH) pre- and postinjection of the radioligand. There
      was a decrease of specifically bound 18F-fallypride as well as evidence of an
      enhanced clearance of specifically bound 18F-fallypride after administering AMPH
      in the two monkeys. The dissociation rates, k(off), of 18F-fallypride without
      AMPH was <10(-4) min(-1) but after 25 min preadministration of AMPH (1 mg/kg), it
      was 4.1 x 10(-3) min(-1) and after 17, 45 and 90 min postadministration of AMPH
      (1 mg/kg) it was 3.6 x 10(-3) to 4.0 x 10(-3) min(-1). Lower doses of AMPH (0.25
      mg/kg) had a reduced effect on the binding of 18F-fallypride. No effect was seen
      until about 30 minutes after the injection of AMPH. Studies with various doses
      indicated that 18F-fallypride has a maximum response at doses of 0.75-1.50 mg/kg,
      with an approximately 16%/hour reduction in binding. These results indicate that
      AMPH stimulated release of endogenous dopamine reduces the specific binding of
      18F-fallypride.

PMID- 9268061
TI  - Vasopressin and oxytocin immunoreactive neurons and fibers in the forebrain of
      male and female common marmosets (Callithrix jacchus).
AB  - Vasopressin (AVP) and oxytocin (OT) immunoreactive (ir) neurons and fibers were
      examined in the forebrain of male and female common marmosets (Callithrix
      jacchus). As expected from previous studies of cell distribution in the rodent
      and primate brain, AVP-ir cells were most evident in the paraventricularis,
      supraopticus, and suprachiasmaticus of the hypothalamus. AVP-ir cells were also
      widely distributed in the lateral hypothalamus and the bed nucleus of the stria
      terminalis. A sexually dimorphic pattern of AVP-ir cells was found in the bed
      nucleus of the stria terminalis, in which males had more AVP-ir cells than
      females. OT-ir cells were found in the paraventricularis and supraopticus of the
      hypothalamus as well as in the bed nucleus of the stria terminalis and the medial
      amygdala. Male and female marmosets did not differ in the distribution of OT-ir
      cells. Fibers for both AVP and OT were evident outside of the hypothalamic
      neurohypophyseal tract, but a plexus of AVP-ir fibers in the lateral septum or
      lateral habenular nucleus, as seen in the rat brain, could not be detected for
      either peptide.

PMID- 9268062
TI  - Local cerebral metabolic effects of the novel cocaine analog, WF-31: comparisons
      to fluoxetine.
AB  - The effects of the acute administration of the selective serotonin uptake
      inhibitor, fluoxetine, on rates of local cerebral glucose utilization in rats
      were compared to those of the novel cocaine analog, [2beta-propanoyl-3beta-(4
      isopropylphenyl)-tropane, WF-31, which has greater affinity for serotonin than
      dopamine transporters, using the quantitative autoradiographic 2
      [14C]deoxyglucose method. Locomotor activity was assessed simultaneously.
      Fluoxetine administration resulted in dose-dependent decreases in locomotor
      behavior, as well as widespread reductions in rates of metabolic activity in
      brain areas including raphe nuclei, dorsal and ventral striatum, amygdala,
      hippocampus, limbic cortex, and thalamus. These effects were largely concentrated
      in brain regions containing high densities of serotonin transporters as revealed
      by in vitro autoradiography. In contrast, the acute administration of WF-31
      produced more discrete changes in metabolic activity that were localized within
      the raphe nuclei and in portions of the hippocampal formation. Blockade of WF
      31's dopaminergic effects by pretreatment with the antagonist, alpha
      flupenthixol, resulted in a pattern of metabolic changes that closely resembled
      that observed with fluoxetine. These data suggest that the alterations in
      functional activity produced by both fluoxetine and WF-31 are largely the result
      of actions on serotonergic systems.

PMID- 9268063
TI  - Thyroid hormones and the treatment of depression: an examination of basic
      hormonal actions in the mature mammalian brain.
AB  - Numerous clinical reports indicate that thyroid hormones can influence mood, and
      a change in thyroid status is an important correlate of depression. Moreover,
      thyroid hormones have been shown to be effective as adjuncts for traditional
      antidepressant medications in treatment-resistant patients. In spite of a large
      clinical literature, little is known about the mechanism by which thyroid
      hormones elevate mood. The lack of mechanistic insight reflects, in large part, a
      longstanding bias that the mature mammalian central nervous system is not an
      important target site for thyroid hormones. Biochemical, physiological, and
      behavioral evidence is reviewed that provides a clear picture of their importance
      for neuronal function. This paper offers the hypothesis that the thyroid hormones
      influence affective state via postreceptor mechanisms that facilitate signal
      transduction pathways in the adult mammalian brain. This influence is
      generalizable to widely recognized targets of antidepressant therapies such as
      noradrenergic and serotonergic neurotransmission.

PMID- 9268064
TI  - Distribution of the 5-hydroxytryptamine2C receptor protein in adult rat brain and
      spinal cord determined using a receptor-directed antibody: effect of 5,7
      dihydroxytryptamine.
AB  - A synthetic peptide, corresponding to the N-terminal decapeptide (+Y11C12) of the
      rat 5-hydroxytryptamine2C (5-HT2C) receptor protein was used to produce a sheep
      polyclonal antiserum. Western blot analysis showed that the resultant antibody
      G241 recognised two membrane proteins, one (55 kDa) approximating the molecular
      mass of the 5-HT2C receptor (52 kDa) and a second (63 kDa), which may be a
      glycosylated form of the receptor protein. HEK 293 cells transfected with human 5
      HT2C cDNA displayed intense cell surface immunoreactivity with the 5-HT2C
      antiserum, which was completely prevented by incubating the antibody with the
      synthetic 5-HT2C peptide (10 microM), whilst neither non-immune serum nor
      untransfected cells displayed any immunoreactivity. A radioimmunoassay was
      developed to quantify the regional distribution of 5-HT2C-like immunoreactivity
      (LI) in the adult rat brain. The choroid plexus contained five-fold higher levels
      of 5-HT2C-LI than any brain region but high levels were found in the frontal
      cortex, septum, hypothalamus, and striatum, intermediate levels in the thalamus
      and midbrain, and lower levels in brainstem, cerebellum, and spinal cord. In rat
      cortical membranes, the B(max) value from [3H]-mesulergine binding was ten-fold
      lower than 5-HT2C-LI levels determined by radioimmunoassay, which may reflect
      measurement of internalised receptor protein by radioimmunoassay which is not
      detected with conventional 5-HT2C ligands. Ten days after depletion of 5-HT with
      the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), there was a
      significant increase in 5-HT2C-LI in the choroid plexus and the ventral cervical
      spinal cord, suggesting that receptors therein are located post-synaptic to
      destroyed serotonergic nerve terminals. In contrast, the significant reduction in
      5-HT2C-LI observed in the midbrain, brainstem, and dorsal thoracic spinal cord
      following 5,7-DHT implies that 5-HT2C receptors may be located on 5-HT nerve
      terminals in these regions.

PMID- 9268065
TI  - Age-related change in short-term synaptic plasticity intrinsic to excitatory
      striatal synapses.
AB  - Aging disrupts the expression of synaptic plasticity in many central nervous
      system (CNS) structures including the striatum. We found age differences in
      paired-pulse plasticity to persist at excitatory striatal synapses following
      block of gamma aminobutyric acid (GABA)A and GABA(B) receptors, a property that
      was independent of the number of afferents activated. High Mg2+/low Ca2+
      artificial cerebral spinal fluid (ACSF) reduced release probability and
      consequently the size of the evoked excitatory post-synaptic potential (EPSP).
      High Mg2+/low Ca2+ ACSF also increased the expression of paired-pulse
      facilitation and eliminated the age difference seen previously in normal ACSF.
      These data suggest that age differences in paired-pulse plasticity reflect an
      alteration in release probability at excitatory striatal synapses. In support of
      this hypothesis, we found age differences in another presynaptic form of
      plasticity referred to as synaptic augmentation. Examination of the synaptic
      depression that developed during the conditioning tetanus also revealed an age
      related increase in synaptic depression. These data indicate that age-related
      changes in facilitation may be due in part to a reduction in the readily
      releasable pool of synaptic vesicles. Dendritic structure (spine density and
      dendritic length) was correlated with short-term synaptic plasticity, but these
      relationships depended upon the variance associated with age (hierarchical
      regression). Post-hoc within-age group regressions demonstrated relationship
      between spine density and paired-pulse plasticity. No other age-specific
      correlations were found. These findings imply an age-dependent association
      between altered dendritic morphology and changes in synaptic plasticity.

PMID- 9268066
TI  - Endogenous and exogenous nitric oxide in the pedunculopontine tegmentum induces
      sleep.
AB  - Mesopontine cholinergic cells in the pedunculopontine tegmental (PPT) nuclei
      modulate the control of the wake-sleep cycle by releasing acetylcholine to their
      target structures. These cells also synthesize nitric oxide (NO) which diffuses
      into the extracellular space and acts as a neuronal messenger. The present study
      is based on the hypothesis that NO synthesis and its presence in the
      extracellular space in the PPT play a functional role in regulating the
      behavioral states of waking and sleep. This hypothesis was tested by
      microinjecting a control vehicle, NO donor, S-Nitroso-N-acetylpenicillamine
      (SNAP) and a competitive inhibitor of NO synthase enzyme (NOS), N(G)-Nitro-L
      arginine methylester hydrochloride (L-NAME) into the PPT while quantifying the
      effects on wakefulness and sleep. Six cats were implanted with bilateral guide
      tubes for PPT microinjection and with standard electrodes to measure waking, slow
      wave sleep (SWS), and rapid eye movement (REM) sleep. Five-hour free-moving
      polygraphic recordings were made following each microinjection (0.25 microl) of
      control saline, SNAP or L-NAME. Following microinjection of SNAP into the
      cholinergic cell compartments of the PPT, SWS and REM sleep were increased by
      41.65% and 72.10% respectively, compared to the control microinjection.
      Microinjection of L-NAME reduced SWS and REM sleep by 40.33% and 62.05%,
      respectively, compared to controls. The present results demonstrate that
      endogenous NO synthesized within the PPT cholinergic cells functions as a
      paracrine signal in the control of waking and sleep by modulating local
      cholinergic cells.

PMID- 9268067
TI  - Serotonin 5-HT2A receptors are expressed on pyramidal cells and interneurons in
      the rat cortex.
AB  - The distribution of 5-HT2A receptors in rat cortex was evaluated using newly
      developed antibodies. Each of three antibodies tested identified an identical
      pattern of 5-HT2A-like immunoreactivity (5-HT2A-li) in rat cortex with 5-HT2A-li
      showing a widespread distribution. The majority of 5-HT2A-li cells displayed a
      pyramidal morphology. While a minority, some cortical neurons with a bipolar
      morphology displayed 5-HT2A-li as well. Dual-label fluorescence confocal
      microscopic studies with a 5-HT2A antibody and a mouse monoclonal antibody to
      parvalbumin, a marker of a subset of gamma aminobutyric acid (GABA)ergic
      interneurons in the cortex, demonstrated that although some cells expressing 5
      HT2A-li were interneurons, most were not.

PMID- 9268068
TI  - Regulation of central serotonin transporters by chronic lithium: an
      autoradiographic study.
AB  - The objectives of this study were to further characterize the effects of a
      chronic lithium (Li+) treatment on serotonin (5-HT) uptake sites, and to
      determine the eventual reversibility of the observed effects. Quantitative
      autoradiography experiments were carried out on sections from rat brain, using
      [3H]citalopram to label selectively the 5-HT transporters or uptake sites. In
      these experiments, we were able to saturate the 5-HT transporters using an
      isotopic dilution of the radioligand. The lowest densities of [3H]citalopram
      binding were measured in all cortical regions studied, with the highest cortical
      labelling in the anterior cingulate cortex. The rostral neostriatum presented a
      moderate density of labelling, with slightly higher levels in its ventral
      portion. Relatively high densities were measured in the globus pallidus,
      hippocampus, and hypothalamus. Finally, the highest densities were found in the
      brain stem. Indeed, the dorsal raphe nuclei as well as the substantia nigra were
      characterized by very high amounts of [3H]citalopram binding. The chronic
      administration of Li+ increased the density of 5-HT uptake sites in cortical
      regions, and significant differences were observed in the frontal, temporal, and
      entorhinal-piriform cortices, with an elevation, albeit not significant, in the
      anterior cingulate region. A significant increase was also observed in the
      lateral hypothalamus. Since the 5-HT uptake sites were studied with saturating
      concentrations of citalopram, we can propose that this increase in binding
      densities can be attributed to an increase in the number of 5-HT transporters.
      Interestingly, the only modifications observed were located in regions containing
      nerve terminals of 5-HT neurons, while regions with cell bodies remained
      unaffected. Moreover, these effects were completely reversed following a recovery
      of 48 h without Li . Also, there were no modifications in the density of 5-HT
      uptake sites after only 2 days of Li+. These results, suggesting an anatomically
      heterogenous increase in 5-HT uptake in chronically treated rats, are in accord
      with clinical observations and previous reports with homogenate binding assays.
      Finally, the conclusions from this study further support the importance of
      central 5-HT synaptic transmission in the pathophysiology and treatment of human
      affective disorders.

PMID- 9268069
TI  - Ultrastructural localization of CART (cocaine- and amphetamine-regulated
      transcript) peptides in the nucleus accumbens of monkeys.
AB  - CART (cocaine- and amphetamine-regulated transcript) peptides are proposed to
      play a role in the action of psychostimulants as
      neurotransmitters/neuromodulators. In the present study, we demonstrate that the
      shell of the nucleus accumbens, a brain structure involved in drug reinforcement,
      is densely innervated by a dense plexus of CART peptide-immunoreactive varicose
      fibers in register with immunoreactive perikarya in monkeys. At the electron
      microscopic level, varicosities appeared as immunoreactive axon terminals packed
      with round electron-lucent vesicles and a variable number of darkly stained dense
      core vesicles that formed symmetric synapses with dendrites. These findings
      suggest that CART peptides may be a cotransmitter with gamma aminobutyric acid
      (GABA) in intrinsic axon collaterals of striatal projection neurons or
      interneurons in the primate nucleus accumbens.

PMID- 9268070
TI  - Real-time direct volume rendering in functional magnetic resonance imaging.
AB  - Direct volume rendering is a visualization method that allows display of all
      information hidden in three-dimensional data sets of, for example, computed
      tomography or magnetic resonance imaging (MRI). In contrast to commonly used
      surface rendering methods, these algorithms need no preprocessing but suffer from
      a high computational complexity. A real-time rendering system, VIRIM (Vitec:
      Visualization Technology GmbH, Mannheim, Germany), cuts down rendering times of
      minutes on normal workstations to an interactive rate of 1 second or less. The
      immediate visual feedback allows interactive steering of the visualization
      process to achieve insight into the internal three-dimensional structure of
      objects. Additional information is obtained by using an interactive gray-value
      segmentation tool that both allows segmentation of the data set according to
      bone, tissue, and liquor and display of multifunctional data sets (e.g.,
      functional MRI [fMRI] data sets). Thus, real-time direct volume rendering allows
      segmentation and volume data processing of functional and anatomical MR data sets
      simultaneously. As this method can be integrated in the clinical routine, it is
      of great importance for real-time motion artifact detection and the
      interpretation of fMRI data acquired during cognitive experiments with normal
      subjects and psychiatric patients. Because of the free programmability of VIRIM,
      more complex matching procedures are currently being investigated for future
      implementation.

PMID- 9268071
TI  - Volumetric measurement of human calf muscle from magnetic resonance imaging.
AB  - Muscle mass is a determining factor in skeletal muscle function and is affected
      by inactivity, immobilization, disease, and aging. The aim of this study was to
      develop an objective and time-efficient method to quantify the volume and cross
      sectional area of human calf muscles using three-dimensional magnetic resonance
      images. We have estimated the errors incurred in muscle volume measurements
      arising from artifacts known to occur in magnetic resonance imaging (MRI). The
      largest source of error was due to partial volume effects, which resulted in
      overestimation of phantom volumes ranging from 145 to 900 cc by 6% to 13%. The
      magnitude of this effect has been shown to increase with decreasing object size
      and decreasing spatial resolution. We have presented a straightforward correction
      for this effect, which has reduced the volume measurement error to less than 4%
      for all cases. Through the use of computer simulations, the correction algorithm
      has been shown to be independent of object shape and orientation. To reduce user
      subjectivity, a semiautomated computer program has been developed to segment MRI
      data for particular muscle groups. Images from seven human subjects were analyzed
      by the program, yielding muscle volumes of 154.2 +/- 23.2, 281.2 +/- 35.8, and
      432.2 +/- 83.7 for the lateral gastrocnemius, medial gastrocnemius, and soleus,
      respectively.

PMID- 9268072
TI  - In vivo electron spin resonance analysis of nitroxide radicals injected into a
      rat by a flexible surface-coil-type resonator as an endoscope- or a stethoscope
      like device.
AB  - The flexible surface-coil-type resonator (FSCR) operating in a 700 MHz microwave
      electron spin resonance (ESR) system was applied to measure the nitroxide
      radicals at a specific area in rats. The FSCR was composed of a single-turn coil
      with a diameter of 5 mm and two flexible coaxial lines of 450 mm in length. For
      an endoscope-like application, the FSCR was inserted into the rectum of the rat
      and sequential changes in the ESR signals of the intravenously injected nitroxide
      radical (4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl; TEMPOL or 3-carbamoyl
      2,2,5,5-tetramethylpyrrolidine-1-yloxy; carbamoyl-PROXYL) were measured. The ESR
      signal intensity of the nitroxide decreased according to first-order kinetics.
      For a stethoscope-like application, the FSCR was placed at several sites on the
      abdominal skin of the rats receiving a subcutaneous injection of carbamoyl
      PROXYL, and diffusion and/or metabolism of the radical in the skin was observed.

PMID- 9268073
TI  - Lipid composition changes in normal breast throughout the menstrual cycle.
AB  - The detection of breast cancer in women using magnetic resonance imaging (MRI) is
      increasingly used as a supplement to X-ray mammography. Furthermore, proton MR
      spectroscopy (1H MRS) has detected alterations in lipid profiles that are linked
      with tumor development and progression in human biopsy tissue. Because normal
      "resting" breast is highly active, it is necessary to consider that any
      alterations observed in lipid profiles may not be indicative of breast tumor
      development. The purpose of this study was to assess the changes in lipid
      composition in the breast throughout the menstrual cycle in "normals" using MRS
      at 4.0 T. Five women with no known history of breast disease were subject to
      biweekly MRS breast examinations. MRS results showing water and fat resonances
      revealed cyclic changes in the lipid content throughout the duration of the
      menstrual cycle. In particular, intensity changes were seen in methylene (-CH2-)
      and allylic methylene (CH2CH2*CH=) resonances at 2.1 ppm and 1.3 ppm,
      respectively. These intensity changes assumed a similar cyclic trend for each
      subject over the 28 days that correlate with the follicular, ovulatory, and
      luteal phases of the menstrual cycle. The results obtained may indicate cell
      synthesis or metabolic activity in the breast during the menstrual cycle and
      provide valuable information pertinent to lipid responses associated with breast
      disease.

PMID- 9268074
TI  - Magnetic resonance findings in scuba diving-related spinal cord decompression
      sickness.
AB  - Scuba diving is associated with risk of severe decompression sickness (DCS type
      II), which results from rapid reduction of the environmental pressure sufficient
      to cause the formation into tissue or blood of inert gas bubbles previously
      loaded within tissues as a soluble phase. DCS type II constitutes a unique subset
      of ischemic insults to the central nervous system (CNS) with primarily
      involvement of the spinal cord. Ten patients with diving-related barotrauma
      underwent neurologic examination. Two of them presented progressive sensory and
      motor loss in the extremities at admission and were presumed affected by spinal
      cord DCS. Magnetic resonance imaging (MRI) demonstrated abnormalities in the
      white-matter tracts of the spinal cord in these patients, in each case
      corresponding to an area of the cord believed to be clinically involved. After a
      course of therapeutic recompressions, one patient was able to stand and walk a
      short distance, and MRI revealed a decreased extension of areas of spinal cord
      abnormalities. MRI has proved to be reliable in the detection of pathologic
      changes of spinal cord decompression sickness that were previously undetectable
      by other neuroimaging methods and also has proved to be useful in the follow-up
      during therapeutic hyperbaric recompressions.

PMID- 9268075
TI  - Prediction of pathological tumor volume in clinically localized prostate cancer:
      value of endorectal coil magnetic resonance imaging.
AB  - The purpose of this study was to determine whether endorectal coil magnetic
      resonance imaging (MRI) enables accurate assessment of pathologic tumor volume in
      patients with clinically localized prostate carcinoma. Twenty-four patients with
      biopsy-proved prostate carcinoma underwent MRI at 0.5 T before radical
      prostatectomy. Tumor volumes were determined independently on axial fast-spin
      echo (SE) T2-weighted MR images and whole-mount pathology slides of the surgical
      specimens. At pathology, tumor volumes ranged from 0.17 to 9.42 cm3 (mean +/- SD,
      3.11 +/- 2.99 cm3). A strong correlation (r = .944) was found between
      measurements of tumor volume based on MR images and pathological specimens. The
      error was less than 0.5 cm3 in 14 cases, in the range of 0.5-1 cm3 in 7 cases,
      and more than 1 cm3 in 3 cases. By using an MR tumor volume of 2 cm3 as cutoff
      value, extracapsular tumor spread could be predicted with a sensitivity of 81.2%,
      a specificity of 100%, and an accuracy of 87.5%. Tumor volume determinations
      based on MR images seem to be accurate enough to be helpful in clinical decision
      making.

PMID- 9268076
TI  - Non-breath-hold lung magnetic resonance imaging with real-time navigation.
AB  - Magnetic resonance imaging (MRI) with navigating techniques based on consecutive
      breath-holds demand a level of respiratory control that is often beyond the
      capability of patients with lung disease. The objectives of this investigation
      were to develop and evaluate a navigating technique for lung MRI that does not
      rely on patient cooperation. Navigating techniques were implemented at 0.5 T
      using conventional imaging techniques of short echo-time and imaging during
      normal breathing in the diastolic phase of the cardiac cycle. A column of spins,
      orthogonal to the diaphragm, was excited both immediately before and after the
      imaging segment. These signals were processed in real time to provide the
      position of the lung-diaphragm interface. An imaging segment was considered
      correctly acquired only when the interface position was within the acceptance
      window both before and after the acquisition of the segment. A distribution of
      lung-diaphragm interface positions obtained during normal respiration was
      employed to define the acceptance window. In the case of multislice techniques,
      the position of the lung-diaphragm interface immediately before the imaging
      segment was also employed to decide which phase-encoding step to acquire next,
      therefore reducing the apparent frequency of the respiratory motion. A
      distribution of interface positions, updated in real time, served as a reference
      for the allocation of phase-encoding steps according to diaphragm position. The
      lung images obtained represent a significant advance in image quality, improving
      further the ability of MR to detect and monitor pulmonary disease. Motion
      artifacts were reduced, and images reliably demonstrated smaller vessels, which
      are not normally visible without navigation.

PMID- 9268077
TI  - Distributed large-scale simulation of magnetic resonance imaging.
AB  - The concept and the implementation of a parallelized and spin-based simulator for
      magnetic resonance (MR) imaging is presented. The dynamics of magnetization are
      modeled using the Bloch equation covering arbitrary radiofrequency (RF) pulses,
      gradients, main-field inhomogeneity, and relaxation. A temporal decomposition of
      a given sequence is introduced, leading to basic sequence elements called atoms.
      A concept of spatial sampling of the object by spins is proposed, in the course
      of which Shannon's sampling theorem must be respected. In biomedical MR imaging,
      spins can be modeled as noninteracting entities, permitting an efficient
      parallelization of the simulation. The simulator ParSpin was implemented on a
      heterogeneous, interconnected cluster of workstations based on existing message
      passing libraries. The communication overhead has been kept moderately small. The
      aggregate computing performance of many processors enables the research into very
      complex problems (e.g., three-dimensional or steady-state MR experiments
      requiring up to 10(6) spins). Additionally, ParSpin allows a comprehensive
      visualization for educational purposes.

PMID- 9268078
TI  - Transient global brain ischemia in the rat: spatial distribution, extension, and
      evolution of lesions evaluated by magnetic resonance imaging.
AB  - A newly developed model of transient global ischemia in the rat was evaluated by
      magnetic resonance imaging (MRI) in terms of localization of brain lesions, their
      extent and severity, and temporal evolution. Such a model, consisting of
      bilateral occlusion of common carotid arteries for 10 minutes and mild hypoxia
      (15% O2) for 20 minutes induces delayed neuronal degeneration, necrosis, and
      gliosis (detected histologically and immunohistochemically). Ischemia was
      assessed by full suppression of spontaneous electroencephalographic activity. A
      "hybrid" T2-/diffusion-weighted MR sequence enhancing more effectively the
      contrast between injured and intact tissues as compared to T2-weighted MRI was
      used at 24, 48, 72, and 96 hours and at 7 days postischemia. Twenty hypoxic
      ischemic rats showed a considerable variability in brain damage. In 8, there were
      no MRI-detectable lesions at any interval. In the other 12 rats, the severity and
      extension of neuronal damage varied markedly, but the lesions were always
      localized (monolaterally in 8 and bilaterally in 4 rats) in the occipital,
      temporal, or parietal cerebral cortex. Mainly, they were of intermediate severity
      or were severe (as assessed by MRI hyperintensity) and were accompanied by
      usually less severe lesions in the thalamus and/or caudate putamen. The
      hippocampus was affected moderately or severely in 4 of 12 rats. In most cases,
      there was at 48 hours a considerable growth in severity and/or extension of
      lesions, which usually remained stable at later intervals. In conclusion, MRI
      allowed us to follow brain lesions during the first week in this relatively
      simple and noninvasive model of transient global ischemia.

PMID- 9268079
TI  - Regional proton nuclear magnetic resonance spectroscopy differentiates cortex and
      medulla in the isolated perfused rat kidney.
AB  - Volume-localized proton nuclear magnetic resonance spectroscopy was used as an
      assay of regional biochemistry in the isolated perfused rat kidney. This model
      eliminated artifacts caused by respiratory and cardiac motion experienced in
      vivo. Immersion of the kidney under its venous effluent reduced the
      susceptibility artifacts evoked by tissue-air interfaces. The rapid acquisition
      with relaxation enhancement imaging sequence was used for scout imaging. This
      gave excellent spatial resolution of the cortex, outer medulla, and inner
      medulla. Spectra were then acquired in 10 minutes using the volume-selective
      multipulse spectroscopy sequence from voxels with a volume of approximately 24
      microL located within the cortical or medullary regions. Spectral peaks were
      assigned by the addition of known compounds to the perfusion medium and by
      comparison with spectra of protein-free extracts of cortex and medulla. The
      medullary region spectra were characterized by signals from the osmolytes
      betaine, glycerophosphorylcholine, and inositol. The spectra from the cortex were
      more complex and contained lesser contributions from osmolytes.

PMID- 9268080
TI  - Correctly accounting for radiofrequency spillover in saturation transfer
      experiments: application to measurement of the creatine kinase reaction rate in
      human forearm muscle.
AB  - Measurements based on transfer of magnetization have been widely used to
      calculate reaction rates in systems with slow chemical exchange. In these
      experiments, correction for direct irradiation of the observed resonance is in
      general accomplished by replacing the equilibrium magnetization in the Bloch
      equations by a magnetization obtained in an experiment in which a low power radio
      frequency (RF) pulse is placed contralaterally, that is, at an equal distance
      from the observed resonance as the saturated one but on the opposite side.
      However, the magnetization observed during contralateral irradiation is affected
      not only by direct irradiation but also by chemical exchange. We demonstrate here
      that including this effect leads to a substantial improvement in the accuracy of
      reaction rate determination in steady-state saturation transfer experiments and,
      if incomplete saturation is present, also in transient saturation transfer
      experiments. In steady-state saturation transfer experiments performed in vivo at
      1.9 T, correct interpretation of the contralateral saturation transfer experiment
      resulted in a correction of the creatine kinase reaction rate by approximately
      11% on average.

PMID- 9268081
TI  - Influence of cytosolic pH on in vivo assessment of human muscle mitochondrial
      respiration by phosphorus magnetic resonance spectroscopy.
AB  - The authors present an in vivo phosphorus magnetic resonance spectroscopy
      systematic study on the effects of cytosolic pH on skeletal muscle mitochondrial
      respiration in human calf muscle. In 49 normal subjects, the effect of cytosolic
      pH on kinetics of phosphocreatine and adenosine diphosphate recovery and on
      maximum rate of mitochondrial adenosine triphosphate production (Q(MAX)) was
      evaluated. The results show a strong relationship between the rate of
      postexercise phosphocreatine recovery and the lowest value of cytosolic pH
      reached during recovery from exercise (termed minimum pH; r = 0.89); in contrast,
      both adenosine diphosphate recovery halftime and Q(MAX) were independent of
      cytosolic pH at the end of exercise.

PMID- 9268082
TI  - Measurement of flow in small vessels by magnetic resonance phase mapping
      techniques: an in vitro and in vivo study.
AB  - The measurement of blood flow in small arteries is a potential extension of
      magnetic resonance (MR) angiography. We have compared flow measurements based on
      MR phase mapping with those obtained by Doppler ultrasound and electromagnetic
      flowmetry in both phantom and animal models. Correlation between modalities was
      high for in vitro studies (R2 = 0.93-0.98). In vivo, electrocardiogram-gated MR
      and Doppler ultrasound flow measurements compared to electromagnetic flowmetry
      showed fair correlation coefficients (R2 = 0.73 and 0.66, respectively). However,
      limits of agreement indicated that in small vessels flow measured by the three
      modalities could differ by up to +/-90 mL/min. For both models, arteries in the
      range of 3-6.5 mm in diameter produced complementary errors in area and velocity
      measurements in MR studies. Ungated MR studies showed a reduced agreement (R2 =
      0.88 in vitro, 0.54 in vivo), which may in part be due to poor sampling of the
      velocity pattern. The results show that the high correlation obtained in vitro
      cannot be extrapolated to the in vivo situation, where additional physiological
      and anatomical variables are encountered.

PMID- 9268083
TI  - From molecular structure to Alzheimer therapy.
AB  - Clinical trials in the USA, Japan and Europe have confirmed the hypothesis that a
      steady state increase of acetylcholine resulting from cholinesterase inhibition
      in the brain results in an improvement of cognitive function in mild to moderate
      Alzheimer disease (AD) patients. During the last decade, a systematic effort to
      develop a pharmacological treatment for AD has resulted in two drugs being
      registered for the first time in the USA and Europe for this specific indication.
      Both are cholinesterase inhibitors (ChEI). Based on these first positive results,
      several second generation ChEI are being developed. An additional effect of
      certain ChEI is to maintain cognitive function at a constant level during a 6
      months to one year period of treatment as compared to placebo. It is possible
      that the drug effect is one of slowing down cognitive deterioration. Comparison
      of clinical effects of 5 ChEI demonstrates a rather similar magnitude of
      improvement. For some drugs, this may represent a limit, while for others it may
      be possible to increase the benefit further. To maximize and prolong positive
      drug effects, it is important to start early and adjust the dosage during the
      treatment. Other strategies may involve combinations with other cholinergic drugs
      such as muscarinic or nicotinic agonists. A second important class of drugs which
      is being developed is that of muscarinic m1 agonists. However, their clinical use
      is still limited by side effects. The increased knowledge and recognition of the
      beta-amyloid molecule as a central focus of AD pathology has strongly stimulated
      research with the hope of finding ways of influencing its processing and
      deposition. At this point, no product in this line of development has reached
      clinical trial level. Other pharmacological approaches are related to preventive
      and neuroprotective interventions (estrogens, anti-oxidants and anti
      inflammatories). In conclusion, given the relatively short time of research in
      this field, results are encouraging.

PMID- 9268084
TI  - Effects of steroid 5alpha-reductase inhibitor ONO-9302 and anti-androgen
      allylestrenol on the prostatic growth, and plasma and prostatic hormone levels in
      rats.
AB  - ONO-9302 [epristeride; (-)-17beta-(tert-butylcarbamoyl)androsta-3,5-diene-3
      carboxy lic acid] is a novel inhibitor of steroid 5alpha-reductase. We studied in
      vitro and in vivo effects of ONO-9302 on the rat prostatic tissue in comparison
      with those of the anti-androgen allylestrenol. ONO-9302 inhibited the rat
      prostatic enzyme with an IC50 value of 11 nM, whereas allylestrenol was about
      80,000-fold less potent. The growth of ventral prostate, which was induced by the
      subcutaneous injection of testosterone propionate in the castrated rats, was
      significantly reduced by ONO-9302 at oral doses of 1-100 mg/kg/day. Allylestrenol
      showed a significant effect only at a dose of 100 mg/kg/day. In mature male rats,
      ONO-9302 significantly reduced the ventral prostate weight at doses of 10-100
      mg/kg/day and decreased prostatic 5alpha-dihydrotestosterone (DHT) content
      associated with a rise in testosterone (T) content at doses of 0.1-100 mg/kg/day.
      Plasma hormone levels (i.e., T, DHT, luteinizing hormone (LH) and follicle
      stimulating hormone (FSH)) were not altered significantly. Allylestrenol
      significantly reduced the ventral prostate weight at doses of 10-100 mg/kg/day.
      However, unlike ONO-9302, allylestrenol reduced both the prostatic DHT and T
      contents and also lowered plasma T, DHT, LH and FSH levels at a dose of 30
      mg/kg/day. These results suggest that ONO-9302 reduces the prostatic growth by
      inhibiting the conversion of T to DHT in the prostate without lowering blood T
      level unlike anti-androgen drugs.

PMID- 9268085
TI  - Neuroprotective effect of YM90K, an AMPA-receptor antagonist, against delayed
      neuronal death induced by transient global cerebral ischemia in gerbils and rats.
AB  - We investigated the neuroprotective effect of the alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionate (AMPA)-receptor antagonist YM90K in transient global
      ischemia models. In a gerbil model, transient ischemia was induced by bilateral
      common carotid artery (CCA) occlusion for 5 min. On administration at 1 hr after
      ischemia, the AMPA antagonists NBQX (30 mg/kg, i.p. x 3) and YM90K (15 mg/kg,
      i.p. x 3 or 30 mg/kg, i.p. x 3) significantly reduced the delayed neuronal death
      in the hippocampal CA1 region from 4 days after bilateral CCA occlusion.
      Furthermore, YM90K (30 mg/kg, i.p. x 3) showed a neuroprotective effect even when
      given at 6 hr after ischemia. In contrast, the N-methyl-D-aspartate receptor
      antagonists CGS19755, MNQX (30 mg/kg, i.p. x 3, each) and (+/-)MK-801 (10 mg/kg,
      i.p.) were not effective on injection at 1 hr after ischemia in this model. In a
      rat model, ischemia was induced by 4-vessel occlusion (4-VO) for 10 min. YM90K
      was administered 60 min after reperfusion. Rectal and temporal muscle
      temperatures were maintained at the same level as in the control group for 6 hr.
      YM90K markedly prevented the development of delayed neuronal death from 7 days
      after 4-VO at doses of 15 or 30 mg/kg, i.p. x 3, with neuroprotective efficacy
      similar to that in the gerbil model. These results suggest that the AMPA receptor
      plays a critical role in the development of the delayed neuronal death induced by
      transient global cerebral ischemia. They also suggest that the neuroprotective
      effect of YM90K is not related to its hypothermic effect.

PMID- 9268086
TI  - Effect of long-term administration of berberine on scopolamine-induced amnesia in
      rats.
AB  - The effect of berberine (BER) on scopolamine (SCOP)-induced amnesia was
      investigated in a step-through passive avoidance task in rats. It was observed
      that BER at the doses of 0.1 and 0.5 g/kg after 7-day or 14-day administration
      significantly improved SCOP-induced amnesia. The anti-amnesic effect of BER after
      14-day administration on the SCOP-induced amnesia was significantly augmented by
      physostigmine or neostigmine, and completely reversed by scopolamine N
      methylbromide. These results suggest that the antiamnesic effect of BER after 14
      day administration may be related to the increase in the peripheral and central
      cholinergic neuronal system activity.

PMID- 9268087
TI  - Species differences in the 5-hydroxytryptamine-induced contraction in the
      isolated distal ileum.
AB  - We investigated the mechanism of 5-hydroxytryptamine (5-HT)-induced contraction
      in the longitudinal muscle of isolated distal ileum from ferrets, piglets and
      rats. 5-HT and 5-methoxytryptamine concentration-dependently contracted the ileum
      of ferrets, piglets and rats. 2-Methyl-5-HT and m-chlorophenylbiguanide
      concentration-dependently contracted the ferret ileum, whereas they had no effect
      in piglets and rats. In ferrets, the 5-HT-induced contraction was inhibited by
      methysergide and by ramosetron, but not by ketanserin or GR113808. Atropine and
      tetrodotoxin suppressed contractions elicited by 5-HT, 2-methyl-5-HT and m
      chlorophenylbiguanide in ferrets, but not that elicited by 5-methoxytryptamine.
      In piglets, 5-HT-induced contraction was inhibited by methysergide and by
      tetrodotoxin, but not by ketanserin, ramosetron, GR113808 or atropine. In rats, 5
      HT-induced contraction was inhibited by methysergide and by ketanserin, but not
      by ramosetron or tetrodotoxin. In contrast, GR113808 enhanced contractions
      elicited by 5-HT or 5-methoxytryptamine. These results suggest that 5-HT-induced
      contraction in ferrets is mediated via 5-HT1 receptors on the muscle and by
      release of acetylcholine via 5-HT3 receptors. In piglets, 5-HT-induced
      contraction appears to be mediated by release of neurotransmitters other than
      acetylcholine via 5-HT1 receptors. 5-HT-induced contraction in rats is evoked via
      5-HT1 and 5-HT2 receptors on the muscle. Furthermore, 5-HT4 receptors may
      participate in the relaxation elicited by 5-HT in rats.

PMID- 9268088
TI  - Flow-dependent regulation of nitric oxide formation in the isolated canine
      mesenteric arterial bed.
AB  - Effects of flow rate changes on nitric oxide (NO) formation in vascular
      endothelial cells were investigated in isolated canine mesenteric arterial bed
      preparations. Stepwise increases in the flow rate from 8 ml/min to 40 ml/min
      significantly (P <0.05) elevated perfusion pressure in a rate-dependent manner.
      In the presence of N(G)-nitro-L-arginine (L-NNA, 100 microM), perfusion pressures
      were significantly (P<0.01) higher than those observed under control conditions
      at all flow rates examined. Sodium nitroprusside (SNP) (0.1-10 microM)
      counteracted the pressor effect of L-NNA in a concentration-dependent manner.
      Increases in the flow rate from 10 ml/min to 40 ml/min significantly (P < 0.05)
      augmented cyclic GMP production in the vascular bed preparation. The flow-induced
      cyclic GMP response was significantly (P <0.05) attenuated by L-NNA (100 microM).
      These results demonstrate that 1) the amount of NO released from endothelial
      cells toward vascular smooth muscle cells can be semi-quantified with SNP, and 2)
      an increase in the flow rate stimulates NO formation in endothelial cells of
      resistance arteries, which may play an important part in regulating systemic
      blood pressure.

PMID- 9268089
TI  - Cimetidine inhibits the induction of long-term potentiation in the dentate gyrus
      of rats in vivo.
AB  - We investigated the effect of cimetidine, a clinically used H2-receptor
      antagonist, on the induction of long-term potentiation (LTP) in the dentate gyrus
      of anesthetized rats. Intracerebroventricular injection of cimetidine (50-100
      nmol) inhibited the induction of LTP in a dose-dependent manner. The inhibitory
      effect of cimetidine was not mimicked by other H2-receptor antagonists
      (ranitidine, famotidine) or the H1-receptor antagonist diphenhydramine or the H3
      receptor antagonist thioperamide. These results suggest that cimetidine inhibits
      hippocampal synaptic plasticity by a novel brain mechanism unrelated to H1, H2 or
      H3 receptors.

PMID- 9268090
TI  - GTS-21, a nicotinic agonist, protects against neocortical neuronal cell loss
      induced by the nucleus basalis magnocellularis lesion in rats.
AB  - Effect of subchronically administered GTS-21 [3-(2,4-dimethoxybenzylidene)
      anabaseine dihydrochloride], a selective nicotinic agonist, on neuronal cell loss
      caused by nucleus basalis magnocellularis (nBM) lesion was studied in rats. After
      2 weeks of bilateral nBM excitotoxic lesion, GTS-21 was orally administered once
      daily for 20 weeks. Neuronal cell loss was observed in layers II-III of the
      parietal cortex in the lesioned control rats. GTS-21 significantly attenuated the
      neuron loss in these layers. These results suggest that GTS-21 exhibits a
      protective action against the neuronal cell death in the parietal cortex and may
      have a beneficial effect on neurodegenerative disorders such as an Alzheimer-type
      disease.

PMID- 9268091
TI  - MODED: microcephaly-oculo-digito-esophageal-duodenal syndrome.
AB  - We report on 4 families with microcephaly, type A brachydactyly, variable
      learning disabilities, short stature, duodenal atresia, patent ductus arteriosus
      (PDA), hallux valgus, restricted elbow and finger movements, and amesophalangy
      and syndactyly of toes. Three previous families manifested all signs of the
      syndrome, and in another four reports the phenotype was incomplete. These cases
      are reviewed. Penetrance of digital and toe anomalies is almost complete and
      microcephaly is present in 78% of known cases. Short stature was present in 70%
      of our cases, but this is probably an overestimation. Esophageal and duodenal
      atresias were present in 25% of known cases. Correction for ascertainment bias
      gave a lower estimate of 16.6%. Learning disabilities were present in 31% of all
      patients. Longitudinal follow-up suggested that hypoplasia or absence of the
      diaphyseal ossification centers is the primary cause of the phalangeal changes.
      Observations in a 9-year-old girl, followed since age 3.3, suggest that the
      eventual absence of the middle phalanges of the toes may be caused by fusion.

PMID- 9268092
TI  - New autosomal-recessive syndrome of Leber congenital amaurosis, short stature,
      growth hormone insufficiency, mental retardation, hepatic dysfunction, and
      metabolic acidosis.
AB  - We report on a new autosomal-recessive syndrome in 4 Japanese children in 2
      families. The key manifestations are Leber congenital amaurosis, short stature,
      growth hormone insufficiency, mental retardation, hepatic dysfunction, metabolic
      acidosis, and autosomal-recessive inheritance. There were no consanguineous
      marriages. Abnormal eye movements were noticed neonatally, and ophthalmological
      examinations showed no visual acuity, pigmentary retinal degeneration, and
      nonrecordable electroretinograms in all cases. Inadequate weight gain and short
      stature gradually became apparent after birth, and at present the height range is
      -4.6 - -7.2 SD (standard deviations). Developmental delay was noted at age 4
      months, and the developmental quotient is 50-70 at present. Deterioration of
      development and convulsions were not recognized. Elevated serum aminotransferase
      levels and metabolic acidosis were also found at age 4 months. Proximal renal
      tubular acidosis was clarified by bicarbonate tolerance tests in 1 case, and may
      have caused metabolic acidosis. Growth hormone secretion was insufficient by
      insulin tolerance test in 3 cases. One year of growth hormone therapy in 2 cases
      did not affect growth velocity. Hepatic dysfunction and metabolic acidosis
      ameliorated later. No renal cysts were found. A cranial computed tomographic scan
      and magnetic resonance imaging showed normal findings. Amino acids, organic
      acids, and very long chain fatty acid levels in plasma were all normal in the 3
      cases examined. Histopathological and mitochondrial DNA analyses showed no
      evidence of mitochondrial disorders.

PMID- 9268094
TI  - Familial broad terminal phalanges with one individual showing additional
      anomalies.
AB  - We describe a family with four relatives showing broad terminal phalanges (BTP)
      of the fingers and toes. One also had mental retardation, an unusual facial
      appearance, cleft palate with bifid uvula, and gingival hyperplasia. The BTP
      anomaly in this family seems to be transmitted as an autosomal dominant trait.

PMID- 9268093
TI  - Hyperlipidemia, insulin-dependent diabetes mellitus, and rapidly progressive
      diabetic retinopathy and nephropathy in Prader-Willi syndrome with
      del(15)(q11.2q13).
AB  - We report on a white man with Prader-Willi syndrome (PWS) and del(15)(q11.2q13),
      confirmed by fluorescence in situ hybridization (FISH), who had hyperlipidemia,
      insulin-dependent diabetes, and the early onset and rapid progression of diabetic
      retinopathy and nephropathy within 4 years after diagnosis of diabetes. The
      spectrum of glucose intolerance in patients with PWS is discussed, as well as
      those references which suggest that the prevalence of hyperlipoproteinemia in
      this condition may be greater than previously recognized. We suggest the need for
      clarification of both the prevalence and types of hyperlipoproteinemia, as well
      as the pathophysiology of glucose intolerance and correlation with molecular
      cytogenetic findings. We also encourage careful monitoring for diabetic
      complications to further clarify the prevalence and possible accelerated course
      of microvascular lesions.

PMID- 9268095
TI  - Novel case of del(17)(q23.1q23.3) further highlights a recognizable phenotype
      involving deletions of chromosome (17)(q21q24).
AB  - We report on a girl with a phenotype and developmental profile initially
      suggestive of Angelman syndrome. Subsequently she was shown to have an
      interstitial deletion of the long arm of chromosome 17; [del(17)(q23.1q23.3)],
      the smallest unique cytogenetic deletion in this region documented to date. These
      findings and those of 4 others from the literature, with overlapping deletions of
      17q and breakpoints between 17q21-17q24, are reviewed and compared. Similar
      phenotypic findings include growth retardation, global developmental delay, and
      specific musculoskeletal and craniofacial anomalies. The size of the specific
      deletion, and the proximal and distal breakpoints at this region of chromosome
      17q, appear to be important in determining morbidity from cardiac involvement and
      may affect the extent of developmental delay.

PMID- 9268096
TI  - Inheritance of familial congenital isolated anorectal malformations: case report
      and review.
AB  - We report on a 3-generation family with 4 members affected with congenital low
      anorectal malformations. The vertical segregation of the anomalies and the
      occurrence of affected males and females support autosomal-dominant inheritance,
      which was suggested previously for this type of congenital anomaly.

PMID- 9268097
TI  - Familial Blomstrand chondrodysplasia with advanced skeletal maturation: further
      delineation.
AB  - We report on two sibs with a rare lethal chondrodysplasia born to a non
      consanguineous couple. The hallmarks of this affection, also called Blomstrand
      chondrodysplasia, are short limbs, polyhydramnios, hydrops fetalis, facial
      anomalies, increased bone density, and a remarkable advance in skeletal
      maturation. We describe the radiologic and pathologic manifestations in these two
      cases. This recurrence affecting a male and a female fetus, born to the same
      couple, suggests autosomal recessive inheritance.

PMID- 9268098
TI  - Relationship between medical genetics and public health: changing the paradigm of
      disease prevention and the definition of a genetic disease.

PMID- 9268099
TI  - Exclusion of BMP6 as a candidate gene for cleidocranial dysplasia.
AB  - Cleidocranial dysplasia (CCD) is an autosomal dominant, generalized skeletal
      dysplasia in humans that has been mapped to the short arm of chromosome 6. We
      report linkage of a CCD mutation to 6p21 in a large family and exclude the bone
      morphogenetic protein 6 gene (BMP6) as a candidate for the disease by cytogenetic
      localization and genetic recombination. CCD was linked with a maximal two-point
      LOD score of 7.22 with marker D6S452 at theta = 0. One relative with a
      recombination between D6S451 and D6S459 and another individual with a
      recombination between D6S465 and CCD places the mutation within a 7 cM region
      between D6S451 and D6S465 at 6p21. A phage P1 genomic clone spanning most of the
      BMP6 gene hybridized to chromosome 6 in band region p23-p24 using FISH analysis,
      placing this gene cytogenetically more distal than the region of linkage for CCD.
      We derived a new polymorphic marker from this same P1 clone and found
      recombinations between the marker and CCD in this family. The results confirm the
      map position of CCD on 6p21, further refine the CCD genetic interval by
      identifying a recombination between D6S451 and D6S459, and exclude BMP6 as a
      candidate gene.

PMID- 9268100
TI  - Intersitial deletion of 20p: new candidate region for Hirschsprung disease and
      autism?
AB  - We describe a patient with Hirschsprung disease and autism. High-resolution
      karyotyping indicated that the patient has an interstitial deletion of 20p11.22
      p11.23. Microsatellite analysis showed a deletion involving a 5-6 cM region from
      the maternally derived chromosome 20. The deleted region is proximal to, and does
      not overlap, the recently characterized Alagille syndrome region. This region of
      20p has not yet been implicated in Hirschsprung disease or autism. However, this
      region contains several genes that could plausibly contribute to any phenotype
      that includes abnormal neural development.

PMID- 9268101
TI  - Mental retardation in Nance-Horan syndrome: clinical and neuropsychological
      assessment in four families.
AB  - Nance-Horan syndrome (NHS) is a rare X-linked condition comprising congenital
      cataract with microcornea, distinctive dental, and evocative facial anomalies.
      Intellectual handicap was mentioned in seven published NHS patients. We performed
      a clinical study focused on psychomotor development, intellectual abilities, and
      behavior in 13 affected males in four NHS families, and present the results of a
      neuropsychological evaluation in 7 of them. Our study confirms that mental
      retardation (MR) can be a major component of the NHS. Combining our data with
      those from the literature leads to a frequency of MR in NHS of around 30%. In
      most cases, MR is mild or moderate (80%) and not associated with motor delay.
      Conversely, a profound mental handicap associated with autistic traits may be
      observed. MR has intra- and inter-familial variability but does not appear to be
      expressed in carriers. Awareness of MR in NHS may be of importance in the
      management of the patients, especially in terms of education. Cloning and
      characterization of the gene and analysis of mutations will be an important step
      towards understanding the molecular basis of mental deficiency in NHS, and in
      delineation from the other XLMR conditions at Xp22.

PMID- 9268102
TI  - Family history: a comprehensive genetic risk assessment method for the chronic
      conditions of adulthood.
AB  - Targeting individuals with increased risk for common, chronic disease can improve
      the efficiency and efficacy of preventive efforts by improving the predictability
      of screening tests and participant compliance. Individuals with the greatest risk
      for these disorders are those with a genetic susceptibility. The purpose of this
      study was to determine the feasibility of using a single, comprehensive family
      history as a method for stratifying risk for many preventable, common genetic
      disorders. Family histories obtained in a prenatal diagnostic clinic were
      reviewed regarding cardiovascular diseases, diabetes and several cancers; 42.5%
      of individuals reported a family history for at least one of the disorders under
      study. Familial coronary artery disease was most commonly reported (29% of
      participants), followed by noninsulin-dependent diabetes (14%). Qualitative
      characterization of disease susceptibility was also accomplished using family
      history data. For example, occurrence of different cancers within pedigrees was
      suggestive of familial cancer syndromes, and clustering of noninsulin-dependent
      diabetes and cardiovascular disease suggested an insulin resistance syndrome.
      Depending on the specific disease, 5 to 15% of at-risk individuals had a
      moderately increased risk (2 to 5 times the population risk), and approximately 1
      to 10% had a high risk (absolute risks approaching 50%). Family history reports
      of common, chronic disease are prevalent among the population at large, and
      collection and interpretation of comprehensive family history data is a feasible,
      initial method for risk stratification for many preventable, chronic conditions.
      These findings may have important implications for disease prevention and
      management.

PMID- 9268103
TI  - Prenatal detection and molecular characterization of a de novo duplication of the
      distal long arm of chromosome 19.
AB  - A tandem duplication of the distal long arm of chromosome 19 was identified in a
      10 week fetus by analysis of chorionic villi. The fetal karyotype from two
      primary cultures was 46,XY,dir dup(19)(q13.2q13.4). The origin of the extra
      material was confirmed by fluorescence in situ hybridization using a chromosome
      19 whole chromosome probe. Parental chromosomes were normal, indicating a de novo
      origin of the extra chromosome material. This is the first case of dup(19q)
      detected by prenatal diagnosis. Molecular studies demonstrated that the
      duplication involved a maternal chromosome 19.

PMID- 9268104
TI  - Fabry disease: molecular carrier detection and prenatal diagnosis by analysis of
      closely linked polymorphisms at Xq22.1.
AB  - Fabry disease is an X-linked recessive inborn error of glycosphingolipid
      catabolism that results from the deficient activity of the lysosomal enzyme alpha
      galactosidase A (alpha-Gal A). A rapid, reliable, and universal linkage method
      was developed for molecular carrier detection and prenatal diagnosis. By
      determining the informativeness and phase of amplifiable intragenic RFLPs (NcoI
      and SacI), flanking RFLPs (DXS94 and DXS17), and flanking microsatellite
      polymorphisms at Xq22.1 (DXS458, DXS454, DXS7424, DXS178, and DXS101), accurate
      carrier detection, and/or prenatal diagnosis was accomplished in three
      prototypic, unrelated Fabry families. All linkage diagnoses were confirmed by
      identification and analysis of the specific alpha-Gal A lesion in each family.
      Thus, molecular carrier detection and prenatal diagnoses can be performed rapidly
      and reliably by linkage analysis with intragenic and closely-linked polymorphisms
      at Xq22.1 in Fabry families whose specific alpha-Gal A lesions have not been
      determined.

PMID- 9268105
TI  - Molecular analysis of the L1CAM gene in patients with X-linked hydrocephalus
      demonstrates eight novel mutations and suggests non-allelic heterogeneity of the
      trait.
AB  - Eight novel mutations were identified in the gene encoding L1CAM, a neural cell
      adhesion protein, in patients/families with X-linked hydrocephalus (XHC)
      providing additional evidence for extreme allelic heterogeneity of the trait. The
      two nonsense mutations (Gln440Ter and Gln1042Ter) result most likely in
      functional null-alleles and complete absence of L1CAM at the cell surface. The
      four missense mutations (Leu482Pro, Ser542Pro, Met741Thr, and Val752Met) as well
      as delSer526 may considerably alter the structure of L1CAM. Interestingly, a
      missense mutation in an XHC family predicting the Val768Ile change in the second
      fibronectin type III domain of L1CAM was found not only in the two affected
      cousins and their obligate carrier mothers but also in two unaffected male
      relatives of the patients. Several possible explanations of this finding are
      discussed; the most likely being that Val768Ile is a rare non-pathogenic variant.
      If this were indeed the case, our data suggest that the XHC in this family is not
      due to a mutation of the L1CAM gene, i.e., that, in addition to the extreme
      allelic heterogeneity of XHC, a non-allelic form of genetic heterogeneity may
      also exist in this trait.

PMID- 9268106
TI  - Are Melnick-Needles syndrome and oto-palato-digital syndrome type II allelic?
      Observations in a four-generation kindred.
AB  - Melnick-Needles syndrome (MNS) is a female-limited skeletal dysplasia inherited
      in a X-linked dominant pattern. Males born to women with MNS may exhibit lethal
      multiple congenital anomalies, but recurrence of this phenotype within one family
      has not been reported. Males with oto-palato-digital syndrome type II (OPD II)
      also demonstrate a multiple congenital anomalies phenotype that includes skeletal
      dysplasia but the maternal phenotype includes only mild craniofacial anomalies.
      These two syndromes have been suggested as being allelic despite differences in
      the described maternal phenotypes. We present a four-generation kindred in which
      four males had a consistent multiple congenital anomalies phenotype. The females
      in this family have skeletal changes characteristic of MNS but have only mild
      craniofacial anomalies and also deafness attributable to ossicular deformity,
      traits more commonly found in OPD II. The expression of manifestations of MNS and
      OPD II in males and females in this kindred further suggest that these syndromes
      are allelic.

PMID- 9268107
TI  - Progressive diaphyseal dysplasia: a three-generation family with markedly
      variable expressivity.
AB  - Progressive diaphyseal dysplasia was found in a 3-generation family including 18
      affected individuals. We describe the clinical and radiographic manifestations in
      6 of 18 patients with this autosomal-dominant bone dysplasia and the good
      symptomatic response to corticosteroid treatment in one of these. The variability
      of manifestations of the disease in this family and in others previously
      described seems to depend on the sex of the patient and the parental origin of
      the mutation. The patients with more severe symptoms are males who inherited an
      allele of paternal origin. We suggest that the progressive diaphyseal dysplasia
      gene has a function in endochondral bone formation and that its mutation is a
      dynamic one with repeat expansion enhanced in father-to-son transmission.

PMID- 9268108
TI  - Proximal interstitial 6q deletion: a recognizable syndrome.
AB  - We report on an 8-year-old boy with a proximal interstitial deletion of the long
      arm of chromosome 6 with breakpoints q13 to q14.2. He has a characteristic facial
      appearance that is seen in several of the previously described cases. Details of
      his clinical course are reviewed and compared with the nine previous reported
      cases of the proximal deletion 6q syndrome.

PMID- 9268109
TI  - Family with Pelizaeus-Merzbacher disease/X-linked spastic paraplegia and a
      nonsense mutation in exon 6 of the proteolipid protein gene.
AB  - We report on a C-to-T transition in exon 6 of the PLP gene in a male with
      Pelizaeus-Merzbacher disease/X-linked spastic paraplegia. The transition changes
      a glutamine at amino acid residue 233 to a termination codon. This premature stop
      codon probably results in a truncated protein that is not functional. Six other
      relatives were analyzed for the mutation and two female carriers were identified.
      Autopsy data on one male are presented.

PMID- 9268110
TI  - Duplication 14(q24.3q31) in a father and daughter: delineation of a possible
      imprinted region.
AB  - A number of clinical reports have described children with a variety of congenital
      anomalies in association with uniparental disomy (upd) of chromosome 14,
      suggesting that at least some genes on chromosome 14 are subject to parent of
      origin, or imprinting, effects. However, little else is known about this putative
      imprinting of chromosome 14. Both maternal and paternal upd have been observed,
      but a consistent phenotype has only been suggested for the former. Here we report
      on a child with developmental delay, microcephaly, distinct facial findings, and
      who has a duplication of 14q24.3q31. The same cytogenetic abnormality was found
      in her phenotypically normal father. We hypothesize that this segment of
      chromosome 14 contains maternally silenced genes, and that this duplicated
      segment defines an imprinted region on chromosome 14. Alternatively, this
      cytogenetic duplication may be unrelated to the girl's phenotypic anomalies, and
      this duplication may contain genes that are not subject to dosage effect.

PMID- 9268111
TI  - Mutation producing alternative splicing of exon 26 in the COL1A2 gene causes type
      IV osteogenesis imperfecta with intrafamilial clinical variability.
AB  - We have characterized a familial form of osteogenesis imperfecta (OI). Following
      the identification by ultrasound of short limbs and multiple fractures in a fetus
      at 25 weeks of gestation, the family was referred with a provisional diagnosis of
      severe OI. We detected subtle clinical and radiological signs of OI in the father
      and in the paternal grandmother of the proposita, who had never received a
      diagnosis of OI. Linkage analysis indicated COL1A2 as the disease locus.
      Heteroduplex analysis of reverse transcription-polymerase chain reaction (RT-PCR)
      amplification products of pro alpha2(I) mRNA from an affected member and
      subsequent sequencing of the candidate region demonstrated the presence of normal
      transcripts and a minority of transcripts lacking exon 26 (54 bp) of COL1A2.
      Sequencing of PCR-amplified genomic DNA identified an A --> G transition in the
      moderately conserved +3 position of the IVS 26 donor splice site. The mutant pre
      mRNA molecules were alternatively spliced, yielding both full-length and deleted
      transcripts that represented less than 30% of the total pro alpha2(I) mRNA. The
      biochemical data on type I collagen synthesized by dermal fibroblasts showed
      intracellular retention of the mutant protein; failure to detect the shortened
      alpha2(I) chains either in the medium or in the cell layer may be the consequence
      of their instability at physiological temperature. These observations justified
      the mild resulting phenotype.

PMID- 9268112
TI  - Use of MRI in genetic studies of endometriosis.

PMID- 9268113
TI  - Thomas syndrome: clinical variability and autosomal recessive inheritance.

PMID- 9268114
TI  - Protein kinase C in central auditory pathways of the rat.
AB  - Protein kinase C is an important intracellular signaling molecule. Many of its
      ten isoforms are highly expressed in brain, and protein kinase C has been
      implicated in the regulation of the activity of receptors of several major
      neurotransmitters, including glutamate, acetylcholine, glycine, and gamma
      aminobutyric acid. These neurotransmitters and their receptors are present in
      central auditory pathways, suggesting their role in auditory signal processing.
      Although they may be important modulators of the function of these
      neurotransmitter receptors, the distribution of protein kinase C isoforms in
      central auditory systems has not been well characterized. By using
      immunocytochemistry with specific antibodies, we studied the distribution of
      immunoreactivity of four isoforms of protein kinase C, betaI, betaII, gamma, and
      gamma, in central auditory systems of rat brain. Each of these protein kinase C
      isoforms was found to have a unique distribution in the auditory brainstem and
      cortex, supporting a role for these isoforms of protein kinase C in different
      aspects of auditory sensory processing.

PMID- 9268116
TI  - Neuroanatomical distribution of vasotocin in a urodele amphibian (Taricha
      granulosa) revealed by immunohistochemical and in situ hybridization techniques.
AB  - Immunohistochemical and in situ hybridization techniques were used to investigate
      the neuroanatomical distribution of arginine vasotocin-like systems in the
      roughskin newt (Taricha granulosa). Vasotocin-like-immunoreactive neuronal cell
      bodies were identified that, based on topographical position, most likely, are
      homologous to groups of vasopressin-immunoreactive neuronal cell bodies described
      in mammals, including those in the bed nucleus of the stria terminalis, medial
      amygdala, basal septal region, magnocellular basal forebrain-including the
      horizontal limb of the diagonal band of Broca, paraventricular and supraoptic
      nuclei, suprachiasmatic nucleus, and dorsomedial hypothalamic nucleus. Several
      additional vasotocin-like-immunoreactive cell groups were observed in the
      forebrain and brainstem regions; these observations are compared with previous
      studies of vasotocin- and vasopressin-like systems in vertebrates. Arginine
      vasotocin-like-immunoreactive fibers and presumed terminals also were widely
      distributed with high densities in the basal limbic forebrain, the ventral
      preoptic and hypothalamic regions, and the brainstem ventromedial tegmentum.
      Based on in situ hybridization studies with synthetic oligonucleotide probes for
      vasotocin and the related neuropeptide mesotocin, as well as double-labeling
      studies with combined immunohistochemistry and in situ hybridization, we conclude
      that the vasotocin immunohistochemical procedures used identify vasotocin-like,
      but not mesotocin-like, elements in the brain of T. granulosa. The distribution
      of arginine vasotocin-like systems in T. granulosa is greater than the
      distribution previously reported for any other single vertebrate species;
      however, it is consistent with an emerging pattern of distribution of vasotocin-
      and vasopressin-like peptides in vertebrates. Complexity in the vasotocinergic
      system adds further support to the conclusion that this peptide regulates
      multiple neurophysiological and neuroendocrinological functions.

PMID- 9268115
TI  - Protein kinase C in central vestibular, cerebellar, and precerebellar pathways of
      the rat.
AB  - The protein kinase C family of enzymes is composed of at least ten different
      isoforms that display a variety of distinct biochemical specificities. Many of
      these isoforms are highly expressed in brain, and some show regional specificity
      in their distribution, suggesting that they may serve specific functions. By
      using immunocytochemistry to localize the betaI, betaII, gamma, or delta isoforms
      of protein kinase C in the central vestibular system of the adult rat, we found
      the vestibular ganglion and its peripheral and central processes of the eighth
      nerve to be heavily labeled with protein kinase C betaI immunoreactivity. Labeled
      axons and terminals were also found in all four vestibular nuclei. Some neurons
      of the vestibular ganglion were weakly stained with the antibody to protein
      kinase C betaII, as were scattered axons in the eighth nerve, and scattered axons
      and terminals were found in all four vestibular nuclei among weakly labeled
      neurons. A few axons in the vestibular portion of the eighth nerve were labeled
      with protein kinase C gamma immunoreactivity, and neurons of the spinal, lateral,
      and superior vestibular nuclei were heavily decorated with synapses, presumably
      derived from Purkinje neurons, which were also strongly immunoreactive. Neurons
      of the medial vestibular nucleus were not as heavily innervated. With the
      antibody to protein kinase C delta, we found scattered, weakly immunoreactive
      neurons in the vestibular portion of the eighth nerve. Myelinated fiber bundles
      of the spinal vestibular nucleus contained moderate numbers of labeled axons, and
      the other vestibular nuclei were well innervated by protein kinase C delta axons
      and terminals. Most of these probably derive from Purkinje cells, which were
      labeled in longitudinal bands interspersed with bands of labeled basket cells.
      These data suggest that particular protein kinase C isoforms play specific roles
      in vestibular and cerebellar function.

PMID- 9268117
TI  - Ultrastructural studies of neuronal correlates of the pubertal reaugmentation of
      hypothalamic gonadotropin-releasing hormone (GnRH) release in the rhesus monkey
      (Macaca mulatta).
AB  - This study tested the hypothesis that puberty in primates is triggered by a
      remodeling of synaptic inputs and/or glial coverage of hypothalamic gonadotropin
      releasing hormone (GnRH) neurons. Male rhesus monkeys were prepubertally
      castrated at 16 months of age and were killed and perfused either 1 month later
      (n = 4, juvenile group) or at 30 months of age, shortly after initiation of the
      pubertal increase in pulsatile GnRH release (n = 4, adult group). Hypothalami
      were sectioned, immunocytochemically stained for GnRH, and processed for electron
      microscopy. Cross-sectional profiles of 77 GnRH cells from the medial basal
      hypothalamus (MBH) and the region of the organum vasculosum of the lamina
      terminalis (OVLT) were compared between the two developmental stages. GnRH cell
      and nucleolus size in the two groups were the same. The percentage of GnRH
      perikaryal membrane occupied by synaptic density in the MBH of juveniles was
      significantly greater (P < 0.05) than that of adults. Differences in the
      percentage of GnRH perikaryal membrane occupied by synaptic density were not
      observed in the OVLT nor on GnRH dendrites in either brain region. Qualitative
      analysis, based on synaptic vesicle shape, failed to reveal developmental
      differences in putatively excitatory or inhibitory synapses on GnRH cells. The
      degree of glial ensheathment of GnRH neurons did not change significantly during
      the two developmental stages. These findings provide ultrastructural evidence for
      the view that, in primates, neuronal plasticity, and specifically a decrease in
      synaptic input to GnRH perikarya, may underlie the initiation of the pubertal
      mode of release of this neuropeptide, and therefore, the onset of puberty in
      these species.

PMID- 9268118
TI  - Neuron numbers in the presubiculum, parasubiculum, and entorhinal area of the
      rat.
AB  - Estimates of neuron numbers have been useful in studies of neurodegenerative
      disorders, and in their animal models, and in the computational modeling of
      hippocampal function. Although the retrohippocampal region (presubiculum,
      parasubiculum, and entorhinal area) is an integral part of the hippocampal
      circuitry and is affected selectively in a number of disorders, estimates of
      neuron numbers in the rat retrohippocampal region have yet to be published. Such
      data are necessary ingredients for computational models of the function of this
      region and will also facilitate a comparison of this region in rats and primates,
      which will help to determine how well we may expect rat models to predict
      function and dysfunction in primate brains. In the present study, we used the
      optical fractionator to estimate the number of neurons in the rat
      retrohippocampal region. The following estimates were obtained: 3.3 x 10(5) in
      presubicular layers II and III, 1.5 x 10(5) in parasubicular layers II and III,
      2.2 x 10(5) in the combined pre- and parasubicular layers V and VI, 6.6 x 10(4)
      in medial entorhinal area (MEA) layer II, 1.3 x 10(5) in MEA layer III, 1.9 x
      10(5) in MEA layers V and VI, 4.6 x 10(4) in lateral entorhinal area (LEA) layer
      II, 1.2 x 10(5) in LEA layer III, and 1.4 x 10(5) in LEA layers V and VI. A
      surprising finding was the large numbers of neurons in the pre- and
      parasubiculum, which indicate an important role of these areas in the control of
      the entorhino-hippocampal projection. A comparison of the numbers of neurons in
      the hippocampus and entorhinal areas in rats with similar estimates in humans
      revealed that gross input-output relations are largely conserved. Differences
      between rats and humans may be accounted for by more prominent entorhino
      neocortical projections in primates and consequent increases in the number of
      neurons in the hippocampus and retrohippocampal region, which are dedicated to
      these projections.

PMID- 9268119
TI  - The timetable of laminar neurogenesis contributes to the specification of
      cortical areas in mouse isocortex.
AB  - In the primate visual cortex, the birthdate of neurons in homologous layers
      differ on either side of the 17-18 border suggesting that there might be
      different timetables of laminar histogenesis in these two areas (Dehay et al.
      [1993] Nature 366:464-466 and Kennedy et al. [1996] Soc. Neurosci. Abst. 22:525).
      Because of the potential importance of these findings for understanding
      mechanisms that generate areal identity, we have developed an experimental
      approach that makes it possible to accurately compute the timetable of laminar
      histogenesis from birthdating experiments. Here we report the results of an
      exhaustive examination of the tempo of layer production in five cortical areas of
      the mouse. Tritiated thymidine pulse injections were made during embryonic
      development and labeled neurons were examined in three frontoparietal areas
      (areas 3, 4, and 6) and two occipital areas (areas 17 and 18a) of the adult
      cortex. The correlation between the radial distribution of neurons and the
      intensities of labeling enabled us to reliably identify first generation neurons
      (i.e., those neurons that quit the cell-cycle in the first round of mitosis after
      injection). For each cortical layer, the percentage of first generation neurons
      with respect to the total number of neurons defined a laminar labeling index.
      Changes of the laminar labeling index over time determined the timetable of layer
      formation. The onset and duration of layer formation was identical in the two
      occipital areas. This finding contrasted with the frontoparietal areas where
      there were important differences in the timing of infragranular and granular
      layer formation and noticeably production of layers VIa, V, and IV occurs earlier
      in area 3 than in area 6. The timing of laminar production of areas 17 and 18a
      resembles more that of area 3 than that of area 6. With respect to areas 3 and 6,
      area 4 shows an intermediate but significantly different timetable of layer
      production. These marked areal differences in the timetable of laminar
      histogenesis contrasted with the relative homogeneity within areas so that we
      have been able to demonstrate that the interareal differences are not merely the
      expression of known neurogenic gradients. These results suggest that in the mouse
      frontoparietal isocortex, neighbouring regions of the ventricular zone that will
      give rise to distinct areas follow distinct programs of layer production. These
      areal differences occur before thalamic innervation and suggest an early
      regionalisation of laminar histogenesis.

PMID- 9268120
TI  - Development of adult-type inhibitory glycine receptors in the central auditory
      system of rats.
AB  - Inhibitory synaptic activity is crucial for many aspects of acoustic information
      processing and mainly mediated by glycine and gamma-aminobutyric acid, the two
      principal inhibitory neurotransmitters in the auditory system. Glycine exerts its
      inhibitory action via binding to postsynaptic receptors existing in various
      isoforms. Here we have investigated the spatiotemporal distribution of adult
      type, strychnine-sensitive glycine receptors (GlyRs) in the rat auditory system
      by using a specific antibody against the ligand-binding alpha1 GlyR subunit. In
      adults, alpha1 GlyRs were found at all relay stations of the auditory pathway
      except for the medial geniculate body and the auditory cortex. In most brainstem
      nuclei, labeling was characterized by dense clusters of heavily immunoreactive
      puncta outlining the somata and proximal dendrites, indicative of a powerful
      glycinergic inhibition. No alpha1 immunoreactivity was seen in the auditory
      system of fetal rats, consistent with results obtained by others in the spinal
      cord. At birth, labeling was weak and restricted to defined nuclei of the
      cochlear nuclear complex and the superior olivary complex. By postnatal day 8,
      labeling was seen in all brainstem nuclei. At the first appearance of
      immunoreactivity, alpha1 GlyRs were diffusely distributed on the neuronal
      surface, yet they became clustered with age, finally densely incrusting the
      somata and proximal dendrites between the 3rd and 4th postnatal week, when the
      mature pattern of immunoreactivity was established. We never observed an
      overexpression of alpha1 GlyRs or a transient appearance in areas that are devoid
      of the receptor in adults. The late formation of glycinergic synapses harboring
      the adult-type GlyRs in the auditory system, at a time when internuclear
      connections have already formed, indicates that alpha1 GlyRs do not participate
      in early synaptogenesis.

PMID- 9268121
TI  - Lateralization and functional organization of the locus coeruleus projection to
      the trigeminal somatosensory pathway in rat.
AB  - The primary goals of this study were to (1) examine the distribution of locus
      coeruleus (LC) neurons, which project to cortical and subcortical sites along the
      trigeminal somatosensory pathway in rats, and (2) determine the extent to which
      different regions within this ascending sensory system receive collateral
      projections from the same LC neuron. Long-Evans hooded rats received unilateral
      pressure injections of different combinations of retrograde fluorescent tracers
      into whisker-related regions of primary (SI) and secondary (SII) somatosensory
      cortices, the ventrobasal (VB) and posterior group (POm) nuclei of the thalamus,
      and the principalis nucleus of the trigeminal complex (PrV). Coronal sections (40
      100 microm) through the LC were examined by fluorescence microscopy, and the
      distribution of retrogradely labeled cells was recorded. The major finding was
      that whisker-related regions of the cortex receive efferent projections from
      neurons concentrated in the caudal portion of the ipsilateral LC, whereas
      subcortical trigeminal somatosensory structures receive bilateral input from both
      LC nuclei. Despite the bilateral nature of the LC projection to subcortical
      sites, the majority of LC efferents to VB and POm thalamus originate in the
      ipsilateral LC nucleus, whereas projections to PrV originate primarily from the
      contralateral LC. An additional finding was that a relatively large proportion of
      LC cells, which project to a single somatosensory structure, also send axon
      collaterals to other relay sites along the same ascending somatosensory pathway.
      Taken together, these results suggest that the LC-noradrenergic system maintains
      a more selective relationship with functionally related efferent targets than has
      been previously appreciated.

PMID- 9268122
TI  - Comprehensive immunofluorescence and lectin binding analysis of vibrissal
      follicle sinus complex innervation in the mystacial pad of the rat.
AB  - The innervation of the vibrissal follicle sinus complexes (FSCs) in the mystacial
      pad of the rat was examined by lectin binding histofluorescence with the B
      subunit of Griffonia simplicifolia (GSA) and by immunofluorescence with a wide
      variety of antibodies for neuronal related structural proteins, enzymes, and
      peptides. Only anti-protein gene product 9.5 labeled all sets of innervation.
      Several types of mechanoreceptors were distributed to specific different targets
      by medium to large caliber myelinated axons. All were positive for 200 kDa
      neurofilament subunit, peripherin, and carbonic anhydrase. Their endings
      expressed synaptophysin. Labeling for the 160 kDa neurofilament subunit,
      calbindin, and parvalbumin varied. Anti-Schwann cell protein S100 was completely
      co-extensive with the axons, terminal arbors, and endings of the mechanoreceptor
      afferents including Merkel innervation. At least 15 different sets of
      unmyelinated innervation were evident based upon distribution and labeling
      characteristics. They consisted of four basic types: 1) peptidergic; 2) GSA
      binding; 3) peptidergic and GSA binding; and 4) nonpeptidergic and GSA negative
      (peptide-/GSA-). Previous studies had not revealed that several major sets of
      unmyelinated innervation were peptide-/GSA-. The unmyelinated innervation had
      detectable peripherin but not 160 kDa or 200 kDa neurofilament subunits. GSA
      positive axons uniquely lacked anti-S100 immunoreactivity. The dense
      circumferentially oriented unmyelinated innervation of the inner conical body
      contained major sets of peptide-/GSA- and GSA innervation as well as a smaller
      peptidergic GSA component. A small contingent of sympathetic and possibly
      parasympathetic innervation was affiliated with microvasculature in the FSCs.
      This study confirms and refutes some previous hypotheses about biochemical and
      morphological relationships between peripheral innervation and sensory ganglion
      cells.

PMID- 9268123
TI  - Comprehensive immunofluorescence and lectin binding analysis of intervibrissal
      fur innervation in the mystacial pad of the rat.
AB  - The innervation of the intervibrissal fur in the mystacial pad of the rat and
      mouse was examined by immunofluorescence with a wide variety of antibodies for
      neuronal related structural proteins, enzymes, and peptides as well as for lectin
      binding histofluorescence with Griffonia simplicifolia (GSA). Anti-protein gene
      product 9.5 (PGP) immunofluorescence labeled all sets of axons and endings. The
      innervation in the upper dermis and epidermis was distributed through a four
      tiered dermal plexus. From deep to superficial, the second tier was the source of
      all apparent myelinated mechanoreceptors, the third tier of nearly all the
      peptidergic and GSA binding innervation, and the fourth tier of nonpeptidergic
      GSA negative innervation (peptide-/GSA-). Three types of mechanoreceptors-Merkel,
      transverse lanceolate, and longitudinal lanceolate endings-innervated guard hair
      follicles. All had similar labeling characteristics for 160 kDa and 200 kDa
      neurofilament subunits, peripherin, carbonic anhydrase, synaptophysin, and S100.
      Palisades of longitudinal lanceolate endings were part of piloneural complexes
      along circumferentially oriented sets of transverse lanceolate endings,
      peptidergic free nerve endings (FNEs), and peptide-/GSA- FNEs. The longitudinal
      lanceolate endings were the only mechanoreceptors in the mystacial pad that had
      detectable calcitonin gene-related peptide. The epidermis contained four types of
      unmyelinated endings: simple free nerve endings (FNEs), penicillate endings,
      cluster endings and bush endings. Only the simple FNEs were clearly peptidergic.
      Virtually all others were peptide-/ GSA-. Each bush ending was actually an
      intermingled cluster of endings formed by several unmyelinated axons and
      occasionally an Adelta axon. In contrast to the other unmyelinated innervation to
      the epidermis, bush endings labeled with an antibody against the Schwann cell
      protein S100. The necks and mouths of follicles, as well as superficial
      vasculature, were innervated by a mixture of unmyelinated peptidergic and/or GSA
      labeled sensory and sympathetic axons. Small presumptive sweat glands were
      innervated by three sets of peptidergic axons of which one was immunoreactive for
      somatostatin. Potential functions of the various sets of innervation are
      discussed.

PMID- 9268124
TI  - Spinal afferents to functionally distinct periaqueductal gray columns in the rat:
      an anterograde and retrograde tracing study.
AB  - The segmental and laminar organization of spinal projections to the functionally
      distinct ventrolateral (vlPAG) and lateral periaqueductal gray (lPAG) columns was
      examined by using retrograde and anterograde tracing techniques. It was found 1)
      that spinal input to both vlPAG and lPAG columns arose predominantly from neurons
      in the upper cervical (C1-4) and sacral spinal cord; 2) that there was a
      topographical separation of vl-PAG projecting and lPAG-projecting neurons within
      the upper cervical spinal cord; but 3) that below spinal segment C4, vlPAG
      projecting and lPAG-projecting spinal neurons were similarly distributed,
      predominantly within contralateral lamina I, the nucleus of the dorsolateral
      fasciculus (the lateral spinal nucleus) and the lateral (reticular) part of
      lamina V. Consistent with the retrograde results, the greatest density of
      anterograde label, within both the vlPAG and lPAG, was found after tracer
      injections made either in the superficial or deep dorsal horn of the upper
      cervical spinal cord. Tracer injections made within the thoraco-lumbar spinal
      cord revealed that the vlPAG column received a convergent input from both the
      superficial and deep dorsal horn. However, thoraco-lumbar input to the lPAG was
      found to arise uniquely from the superficial dorsal horn; whereas the deep dorsal
      horn was found to innervate the "juxta-aqueductal" PAG region rather than
      projecting to the lPAG. These findings suggest that similar to spino-parabrachial
      projections, spinal projections to the lPAG (and juxta-aqueductal PAG) are
      topographically organised, with distinct subgroups of spinal neurons projecting
      to specific lPAG or juxta-aqueductal PAG subregions. In contrast, the vlPAG
      receives a convergent spinal input which arises from the superficial and deep
      dorsal horn of cervical, thoracic, lumbar, and sacral spinal segments.

PMID- 9268125
TI  - Ultrastructural analysis of primary endings in deaf white cats: morphologic
      alterations in endbulbs of Held.
AB  - Changes in structure and function of the auditory system can be produced by
      experimentally manipulating the sensory environment, and especially dramatic
      effects result from deprivation procedures. An alternative deprivation strategy
      utilizes naturally occurring lesions. The congenitally deaf white cat represents
      an animal model of sensory deprivation because it mimics a form of human deafness
      called the Scheibe deformity and permits studies of how central neurons react to
      early-onset cochlear degeneration. We studied the synaptic characteristics of the
      endbulb of Held, a prominent auditory nerve terminal in the cochlear nucleus.
      Endbulbs arise from the ascending branch of the auditory nerve fiber and contact
      the cell body of spherical bushy cells. After 6 months, endbulbs of deaf white
      cats exhibit alterations in structure that are clearly distinguishable from those
      of normal hearing cats, including a diminution in terminal branching, a reduction
      in synaptic vesicle density, structural abnormalities in mitochondria, thickening
      of the pre- and postsynaptic densities, and enlargement of synapse size. The
      hypertrophied membrane densities are suggestive of a compensatory response to
      diminished transmitter release. These data reveal that early-onset, long-term
      deafness produces unambiguous alterations in synaptic structure and may be
      relevant to rehabilitation strategies that promote aural/oral communication.

PMID- 9268126
TI  - Projections from the ventral cochlear nucleus to the dorsal cochlear nucleus in
      rats.
AB  - Local circuit interactions between the dorsal and ventral divisions of the
      cochlear nucleus are known to influence the evoked responses of the resident
      neurons to sound. In the present study, we examined the projections of neurons in
      the ventral cochlear nucleus to the dorsal cochlear nucleus by using retrograde
      transport of biotinylated dextran amine injected into restricted but different
      regions of the dorsal cochlear nucleus. In all cases, we found retrogradely
      labeled granule, unipolar brush, and chestnut cells in the granule cell domain,
      and retrogradely labeled multipolar cells in the magnocellular core of the
      ventral cochlear nucleus. A small number of the labeled multipolar cells were
      found along the margins of the ventral cochlear nucleus, usually near the
      boundaries of the granule cell domain. Spherical bushy, globular bushy, and
      octopus cells were not labeled. Retrogradely-labeled auditory nerve fibers and
      the majority of labeled multipolar neurons formed a narrow sheet extending across
      the medial-to-lateral extent of the ventral cochlear nucleus whose dorsoventral
      position was topographically related to the injection site. Labeled multipolar
      cells within the core of the ventral cochlear nucleus could be divided into at
      least two distinct groups. Planar neurons were most numerous, their somata found
      within the associated band of labeled fibers, and their dendrites oriented within
      this band. This arrangement mimics the organization of isofrequency contours and
      implies that planar neurons respond best to a narrow range of frequencies. In
      contrast, radiate neurons were infrequent, found scattered throughout the ventral
      cochlear nucleus, and had long dendrites oriented perpendicular to the
      isofrequency contours. This dendritic orientation suggests that radiate neurons
      are sensitive to a broad range of frequencies. These structural differences
      between planar and radiate neurons suggest that they subserve separate functions
      in acoustic processing.

PMID- 9268127
TI  - Allatostatin-like-immunoreactive neurons of the tobacco hornworm, Manduca sexta,
      and isolation and identification of a new neuropeptide related to cockroach
      allatostatins.
AB  - The YXFGLamide C-terminus serves to define most members of a family of
      structurally related neuropeptides, the YXFGLamides. These peptides have been
      identified from the nervous system of various insects and include the
      allatostatins of cockroaches and crickets, the schistostatins of locusts, and the
      callatostatins of blowflies. The YXFGLamides have been shown to have various
      functions, including inhibition of juvenile hormone biosynthesis in cockroaches
      and crickets and inhibition of contraction of certain insect visceral muscles. We
      wanted to know if these peptides occur in Manduca sexta and what functions they
      might have. A new peptide, AKSYNFGLamide, was isolated and identified from M.
      sexta and has been named "lepidostatin-1"; this is the first YXFGLamide to be
      found in a lepidopteran, and there are indications that additional YXFGLamides
      occur in M. sexta. An antiserum to cockroach allatostatins (YXFGLamides) was
      shown to recognize lepidostatin-1 of M. sexta and was used to map YXFGLamide
      immunoreactive neurons in larvae. Because immunoreactive interneurons were found
      to form an extensive neuropil, YXFGLamides probably function as neuromodulators
      in M. sexta. Neuroendocrine cells in the brain, abdominal ganglia, and their
      respective neurohemal organs were YXFGLamide immunoreactive and appear to release
      YXFGLamides as neurohormones. Immunoreactivity to YXFGLamides and M. sexta
      diuretic hormone were found to be colocalized and appear to be coreleased in
      these neuroendocrine cells, indicating that YXFGLamides may be involved in
      regulation of fluid transport. Innervation of the corpora allata by YXFGLamide
      immunoreactive processes was very sparse, suggesting that this innervation does
      not play an important role in allatostasis. Many thoracic motor neurons were
      YXFGLamide immunoreactive, suggesting that YXFGLamides may have a myomodulatory
      or myotrophic function in larvae. However, this immunoreactivity disappeared
      early in metamorphosis and did not reappear in the adult. The YXFGLamide
      immunoreactive neurons in the terminal abdominal ganglion were found to innervate
      the hindgut, indicating that YXFGLamides may be involved in the control of the
      rate of myogenic contractions of the larval hindgut.

PMID- 9268128
TI  - Activation by hypotension of neurons in the hypothalamic paraventricular nucleus
      that project to the brainstem.
AB  - To investigate the involvement of neuronal nitric oxide (NO) in the response of
      the brain to changes in blood pressure, we studied the activation of putative NO
      producing neurons in the paraventricular nucleus of the hypothalamus (PVN) in
      rats whose mean arterial pressures (MAPs) were decreased by 40-50% with
      hemorrhage (HEM) or infusion of sodium nitroprusside (NP). Activation was
      assessed on the basis of expression of the immediate early gene, c-fos; putative
      NO-producing neurons were identified with the histochemical stain for
      nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d); and the
      proportions of neurons projecting to the nucleus of the tractus solitarius (NTS)
      and/or caudal ventrolateral medulla (CVLM) were determined with retrograde
      tracing techniques. No differences were found for results obtained from HEM and
      NP animals. Three to four percent of activated PVN neurons projected to the NTS
      or CVLM. Conversely, approximately 33% and 16% of neurons projecting to the NTS
      and CVLM, respectively, were activated. About 43% of NADPH-d neurons in the PVN
      were activated. Of PVN neurons projecting to the NTS or CVLM, 38% and 32%,
      respectively, were NADPH-d positive. About 11% of NADPH-d PVN neurons projected
      to the NTS or CVLM. An average of 3 NADPH-d neurons per section were activated
      and projected to either target. Finally, 7 PVN cells per section sent collateral
      branches to the NTS and CVLM; 2 or 3 of these cells per section were also
      activated by decreases in arterial pressure. No NADPH-d cells were found that
      sent collateral branches to the NTS and CVLM. This study shows that decreases in
      MAP activate PVN neurons that project, singly and through collaterals, to the NTS
      and CVLM. A relatively high proportion of the singly projecting neurons is NADPH
      d positive. These results support the contention that descending projections from
      the PVN to the brainstem play an important role in the physiological response to
      decreases in arterial pressure and suggest that NO may participate in this
      response.

PMID- 9268129
TI  - Dental innervation and CGRP in adult p75-deficient mice.
AB  - Adult dental tissues have unusual neurotrophin biology. Pulpal fibroblasts
      express nerve growth factor (NGF) and the low-affinity p75 neurotrophin receptor,
      their sensory nerve fibers express p75 and trk A, and pulpal sympathetic fibers
      lack p75. Following tooth injury, there is increased pulpal NGF, sprouting of
      sensory nerve endings, and increased immunoreactivity for the sensory
      neuropeptide calcitonin gene-related peptide (CGRP). In the present study, we
      have analyzed tooth structure and innervation of pulp and periodontal ligament in
      young (6-8 weeks, 3 months) and older (5-12 months) adult mice carrying a null
      mutation in the p75 gene and compared the results with those of age-matched wild
      type controls. Our hypotheses were that tooth structure would be abnormal and
      that pulpal innervation would be greatly reduced because it consists primarily of
      nociceptive fibers that have been found to be severely depleted in skin of p75(-/
      ) mice. Tissues were fixed, X-rayed for gross dental morphology, decalcified, and
      analyzed for immunoreactivity for CGRP and for a general nerve marker, protein
      gene product 9.5. Radiographs showed worn-down molar crowns in p75-deficient
      mice. Light microscopy confirmed the accelerated molar wear and showed intense
      CGRP immunoreactivity in pulp nerve endings of mutant mice, compared with a
      gradual decrease in CGRP intensity in controls during normal aging. The CGRP
      intensity in 5-12-month-old pairs of mice was threefold greater in the mutants (P
      < 0.03), and in younger mice the mutant always had more CGRP than its matched
      control. The innervation of molar ligament in all p75-deficient mice was similar
      to that of controls except there was nerve sprouting near bone loss in mutants.
      The incisors of mutant mice did not have unusual wear and their pulpal CGRP
      immunoreactivity remained normal, but their periodontal ligament had fewer thin
      branched nerve endings at all ages. Thus, most innervation of teeth and their
      supporting tissues developed normally, and the only neural changes in p75(-/-)
      mutant mice were the reduction of incisor ligament sensory receptors and
      increased molar CGRP. Sensory nerves in teeth gradually lose neuropeptide
      intensity during aging, but that did not happen in the mutant mice, suggesting
      that the accelerated molar wear stimulated persistent high levels of CGRP.

PMID- 9268130
TI  - Retinal ganglion cells in the albino rat: revised morphological classification.
AB  - Rat retinal ganglion cells were traditionally classified on the basis of soma
      size and the morphology of their dendritic fields. However, in the past,
      techniques used to label ganglion cells (horseradish peroxidase, Golgi, or the
      neurofibrillar stain) did not always stain the axon and/or the entire dendritic
      field. In the present study, we have labelled retinal ganglion cells in the adult
      albino rat with the carbocyanine dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindo
      carbocyanine perchlorate (DiI) or have intracellularly injected them with
      Neurobiotin. Such procedures enabled us to completely fill these neurons, and our
      findings prompted us to modify the existing retinal ganglion cell classification
      in the rat. First, cells were categorised into three groups on the basis of soma
      and dendritic field size: Group RG(A) cells have large somata and dendritic field
      diameters, Group RG(B) cells have small somata and dendritic field diameters,
      whereas Group RG(C) cells have small to medium-sized somata and medium-to-large
      dendritic field diameters. On the basis of dendritic field morphology and
      presence across the retina, each Group was then subdivided into subgroups. The
      significance of our results in terms of retinal ganglion cell function is
      discussed.

PMID- 9268131
TI  - On the origin and frequency of Y chromosome deletions responsible for severe male
      infertility.
AB  - The origin of deletions associated with non-obstructive severe oligozoospermia in
      men are discussed. Deletions could arise during various stages of meiosis, at
      later stages in spermatids, or post-fertilization. Certain embryonic stages may
      be highly sensitive. The possibilities of an inherited propensity to these and
      other deletions, and of mosaicism in embryos are assessed.

PMID- 9268132
TI  - Expression of multiple thyroid hormone receptor mRNAs in human oocytes, cumulus
      cells, and granulosa cells.
AB  - Thyroid hormones have diverse effects on ovarian function. We examined the
      expression of thyroid hormone receptor (TR) mRNAs (including TRalpha-1, TRbeta-1,
      TRbeta-2, and c-erbAalpha-2 isoforms) in three types of cells from human
      follicles, and determined the concentration of free tri-iodothyronine (T3)
      present in human follicular fluid. Human failed-fertilized oocytes, granulosa
      (GC) and cumulus (CC) cells from patients of the in-vitro fertilization (IVF)
      programme at Alliant Hospital Fertility Center were used to detect TR mRNA
      expression using reverse transcription-polymerase chain reaction (RT-PCR)
      followed by Southern blot analysis. Human spermatozoa were also analysed to
      determine whether results obtained with CC would be affected by the presence of
      spermatozoa. beta-Actin mRNA was amplified in each cell type as a positive
      control for the RT-PCR. Our results show that human oocytes express TRalpha-1,
      TRbeta-1, TRbeta-2, and c-erbAalpha-2 mRNAs and that these same isoforms are
      expressed in both human granulosa cells and cumulus cells. No differences were
      detected in the apparent amounts of RT-PCR products when comparing GC with CC,
      suggesting a similar pattern of expression of these RNAs. beta-actin mRNA was
      detected in spermatozoa, but TRalpha-1 expression was not detectable. The
      concentrations of free T3 measured in follicular fluid were similar to, or
      slightly below, those in serum of euthyroid patients. These data demonstrated
      that several isoforms of TR mRNA are expressed in the human oocyte, and hence
      thyroid hormone may have direct affects on the oocyte, as well as on GC and CC.
      In addition thyroid hormone may have indirect effects on the oocytes via the CC.

PMID- 9268133
TI  - Modulation of implantation-associated integrin expression but not uteroglobin by
      steroid hormones in an endometrial cell line.
AB  - In order to test the hypothesis that integrin and uteroglobin (UG) expression in
      cultured endometrial cells are affected by hormone treatment, Ishikawa-CH
      endometrial cancer cells were cultured and exposed to oestradiol or oestradiol
      and progesterone regimens and assayed using immunohistochemistry. We evaluated
      the intensity of immunohistochemical staining for the integrin monomers alpha(v)
      and beta1, the dimers alpha(v)beta3 and alpha(v)beta6, and for the secretory
      protein uteroglobin under various experimental conditions. Cells grown in control
      media stained positively for the integrin monomers alpha(v) and beta1, the dimer
      alpha(v)beta3, and for UG. Oestradiol and sequential oestradiol/progesterone
      reversibly suppressed staining for the dimer alpha(v)beta3. Hormone treatment had
      no effect on the staining of the beta1 and alpha(v) monomers or UG. The
      alpha(v)beta6 dimer antibody did not stain under any experimental treatment
      conditions. These data indicate that expression of the integrin complex
      alpha(v)beta3 is reversibly suppressed by oestradiol in Ishikawa cells and that
      these cells may be a good model for studying hormone-driven molecular changes in
      endometrium.

PMID- 9268134
TI  - Immunohistochemical localization of the LH/HCG receptor in human ovary: HCG
      enhances cell surface expression of LH/HCG receptor on luteinizing granulosa
      cells in vitro.
AB  - We examined the immunohistochemical localization of luteinizing hormone
      (LH)/human chorionic gonadotrophin (HCG) receptor (LH-R) in the human ovary using
      the anti-human LH-R monoclonal antibody, 3B5. In the antral follicles, LH-R was
      detected on theca interna cells. In pre-ovulatory follicles, granulosa cells also
      expressed LH-R. During corpus luteum formation, granulosa cells seemed to
      increase the expression of LH-R, and in corpus luteum of mid-luteal phase, large
      luteal cells expressed LH-R more intensely than small luteal cells. In the
      regressing corpus luteum, LH-R was almost undetectable on both luteal cells,
      whereas in the corpus luteum of early pregnancy, LH-R continued to be expressed
      on large luteal cells. The granulosa cells obtained from the patients undergoing
      in-vitro fertilization therapy were cultured for 3 days in serum-free medium,
      without or with HCG (10 IU/ml) and tumour necrosis factor (TNF)alpha (10 ng/ml).
      Flow cytometry showed that the expression of LH-R on the cell surface of
      luteinizing granulosa cells was enhanced by HCG, but was unaffected by TNFalpha.
      These results suggest that the main target cells for LH/HCG change from theca
      interna cells/small luteal cells to granulosa cells/large luteal cells during
      ovulation, corpus luteum formation, and differentiation into the corpus luteum of
      pregnancy, probably under the influence of LH/HCG.

PMID- 9268135
TI  - Localization of endothelin-1 and endothelin-receptors A and B in human
      epididymis.
AB  - Expression of mRNA of endothelin-1 (ET-1) and its receptors, endothelin receptor
      A (ET-A) and endothelin receptor B (ET-B), in human epididymis was assessed by
      reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemistry
      was performed on longitudinal sections through whole normal human epididymides.
      ET-1 mRNA was detected in caput, corpus and cauda epididymidis.
      Immunohistochemically, ET-1 was localized mainly in ciliated cells of efferent
      ducts and in some principal cells of epididymal duct. Larger arteries, but not
      epididymal microvasculature, contained ET-1 immunoreactivity. ET-A and ET-B mRNAs
      were detected in caput, corpus and cauda epididymidis. In efferent ducts, ET-A
      immunoreactivity was localized in ciliated cells. In the proximal region of the
      epididymal duct, ET-A immunostaining was localized mainly in basal cells whereas
      the distal region was devoid of ET-A immunoreactivity. Throughout the epididymis,
      blood vessels stained positive for ET-B. Furthermore, ET-B immunoreactivity was
      found in ciliated cells of efferent ducts and in basal cells of the distal
      epididymal duct. The fact that ciliated cells of efferent ducts contain ET-1 and
      both types of receptors indicates that ET-1 acts as an autocrine factor in these
      cells. ET-1 produced by efferent ducts and epididymal duct may control epididymal
      blood flow in a paracrine manner via ET-B receptors in epididymal blood vessels.

PMID- 9268136
TI  - Detection of chromosomes and estimation of aneuploidy in human spermatozoa using
      fluorescence in-situ hybridization.
AB  - The development and application of fluorescence in-situ hybridization (FISH) has
      opened the way for comprehensive studies on numerical chromosome abnormalities in
      human spermatozoa. FISH can be rapidly applied to large numbers of spermatozoa
      and thus overcomes the major limitation of karyotyping spermatozoa after
      penetration of zona-free hamster oocytes. The simultaneous hybridization of two
      or more chromosome-specific probes to spermatozoa and subsequent detection of the
      bound probes using different fluorescent detection systems enables two or more
      chromosomes to be localized simultaneously in the same spermatozoon and provides
      a technique for undertaking reasonable estimates of aneuploidy. The most commonly
      used probes are those which bind to the centromeric region of specific
      chromosomes. Most studies to date have concentrated on estimating aneuploidy in
      spermatozoa from normospermic men, although reports are beginning to appear on
      aneuploidy in spermatozoa from subfertile and infertile men. Multi-probe FISH
      studies have generally reported disomy (hyperhaploidy) estimates of 0.05-0.2% per
      chromosome. There is preliminary evidence that some chromosomes such as X, Y and
      21 are predisposed towards higher rates of non-disjunction during
      spermatogenesis. There are also suggestions of inter-donor variability in
      aneuploidy frequencies for specific chromosomes, although this requires
      confirmation in larger studies. While FISH is clearly a powerful technique that
      has many applications in reproductive medicine, it must also be realized that it
      does have limitations and the technology itself is still evolving and has yet to
      be fully validated on spermatozoa.

PMID- 9268137
TI  - Carbohydrates and fertilization: an overview.
AB  - Initial sperm-egg binding in mammals involves recognition of glycosylated
      proteins of egg zonae by glycosylated proteins on sperm surfaces. Egg zona
      protein structure is relatively simple, and has been strongly conserved. Species
      specificity must reside in the carbohydrate modifications on the egg surface, and
      in the co-ordinated assembly of a unique cohort of sperm proteins at
      capacitation. Fruitful advances have been made along four lines. Oligosaccharide
      structures capable of binding spermatozoa have been dissected by in-vitro
      synthesis and binding experiments, informed by the general advance of knowledge
      of protein glycosylation processes. Site-specific mutagenesis of zona proteins
      and their expression in tissue culture have identified glycosylation sites
      involved in species-specific sperm binding. Antibody and lectin labelling studies
      show a continuing process of remodeling of glycosylated sperm surface epitopes
      within a set of stable compartments during epididymal transit and capacitation of
      spermatozoa. Characterization of sperm-egg binding proteins from a variety of
      mammalian species shows that a different set of effectors induce acrosome
      reactions in each species, with each set including one or more sugar-recognizing
      proteins. Sequencing of some of these effectors suggests that each group may form
      a supermolecular complex to induce a species-specific acrosome reaction, with the
      functional activities distributed in a species limited or non-limited manner
      among the individual proteins.

PMID- 9268138
TI  - Meshwork arrangement of mitochondria-rich, Na+,K+-ATPase-rich cells in the
      saccular epithelium of rainbow trout (Oncorhynchus mykiss) inner ear.
AB  - BACKGROUND: Electrolyte composition of the teleost fish inner ear endolymph is
      characterized by a high potassium concentration. From the ultrastructural
      characteristics, the mitochondria-rich cells (MRCs) in the inner ear epithelium
      are suggested to regulate the ionic composition of the endolymph. METHODS: In the
      present study, the ultrastructure of MRCs in the saccular epithelium of the
      rainbow trout (Onchorhynchus mykiss) was studied, and the immunocytochemical
      detection of Na+,K+-ATPase, the key enzyme of the ion-transport, in the saccular
      epithelium was conducted. Electrolyte composition of the saccular endolymph was
      also determined. RESULTS: Electron-microscopic observations revealed that MRCs
      located at the periphery of the sensory macula have numerous elongated
      mitochondria and a well-developed tubular system. Immunocytochemical detection of
      Na+,K+-ATPase on paraffin sections showed that immunoreactive (ir-) cells were
      distributed specifically around the sensory macula. Judging from their shape,
      size, and localization, the Na+,K+-ATPase ir-cells corresponded to the MRCs. The
      whole-mount immunocytochemistry using Na+,K+-ATPase as a marker for the MRC
      revealed that MRCs were connected with one another by extended cellular
      processes, and thus forming a dense meshwork structure around the macula. In the
      endolymph, potassium levels were 13 times higher than those in plasma, chloride
      levels were slightly higher whereas sodium, calcium, magnesium, and phosphate
      levels were lower. CONCLUSIONS: Thus, the saccular MRCs abundant in Na+,K+-ATPase
      are distributed around the sensory macula forming a dense meshwork structure,
      with the suggested function to regulate the electrolyte composition of the
      saccular endolymph.

PMID- 9268139
TI  - Endothelin and nitric oxide synthase in lymphatic endothelial cells:
      immunolocalization in vivo and in vitro.
AB  - BACKGROUND: Endothelin (ET) is an endothelium-derived multifunctional peptide
      that produces a potent, long-lasting vasoconstriction. Nitric oxide (NO), besides
      being the most important endothelium-derived relaxant factor in blood vessels, is
      supposed to be involved in regulating the interactions among endothelium,
      adhesive molecules, and leukocytes. METHODS: We investigated the possible
      occurrence and distribution of ET and constitutive nitric oxide synthase (NOs),
      the enzyme that generates NO from L-arginine, in bovine lymphatic vessels and
      primary culture of lymphatic endothelium by using immunocytochemistry. RESULTS:
      Specific immunostaining with both ET and endothelial constitutive NOs antisera
      was detectable at light and electron microscopic levels in the endothelial cell
      layer of lymphatic vessels, whereas no immunostaining could be observed in the
      muscular and adventitial layers. The immunoreaction showed a diffuse pattern
      throughout the cytoplasm of endothelial cells. Primary cultures of endothelial
      cells isolated from lymphatic vessels also displayed cytoplasmic ET- and NOs-like
      immunoreactivities. The endothelial nature of cell monolayers was confirmed by
      the positive reaction to the von Willebrand factor, a reliable marker of
      endothelial cells, and by ultrastructural features of cultured cells.
      CONCLUSIONS: These findings suggest that the endothelium is a major source of ET
      and NO in lymphatic vessels. Interestingly, the lymphatic endothelium maintains
      the capability of producing such vasoactive sustances also in vitro, thus
      suggesting that lymphatic endothelial cells in culture may be used in studies
      concerning the role of the endothelium in the generation of vasoactive molecules.
      According to previous functional studies, the occurrence of ET and NOs
      immunoreactivities in lymphatic vessel endothelium supports the view that
      lymphatic endothelium may play an important role in the regulation of lymphatic
      vascular tone and in the production of vascular contractile activity promoting
      lymph flow.

PMID- 9268140
TI  - Intraalveolar bubbles and bubble films: III. Vulnerability and preservation in
      the laboratory.
AB  - BACKGROUND: Having confirmed (Scarpelli et al. 1996. Anat. Rec. 244:344-357 and
      246:245-270) the discovery of intraalveolar bubbles and films as the normal
      anatomical infrastructure of aerated alveoli at all ages, we now address three
      questions. Why have these structures been so elusive? Visible in fresh lungs from
      the in vivo state, can they be preserved by known laboratory methods? Can they be
      preserved intact for study in tissue sections? METHODS: Lungs of adult rabbits
      and pups were examined in thorax directly from the in vivo state to confirm
      normal bubbles both at functional residual capacity and at maximal volume; other
      lungs were permitted to deflate naturally to minimal volume. The fate of bubbles
      in situ (either intact, transected, or diced lung tissue) and of isolated bubbles
      was assessed (1) during conventional histopreparative processing, (2) during
      inflation-deflation after degassing, (3) after drying in air, (4) during and
      after quick freezing in liquid N2, and (5) after preservation in fixed and
      stained tissue sections prepared by a new double-impregnation procedure in which
      glutaraldehyde-fixed tissue was preembedded in agar, dehydrated and clarified
      chemically, embedded in paraffin, sectioned, and stained. Control studies
      included both blocking of bubble formation by rinsing the air spaces with Tween
      20 prior to double impregnation and preparation of normal tissue without
      preembedding in agar. RESULTS: (1) Each of the following procedures in
      conventional processing dislocated and disrupted bubbles and films: osmium
      tetroxide and glutaraldehyde:formaldehyde:tannic acid mixture fixation; chemical
      dehydration (70-100% ethanol) and clarification (xylene and acetone); and
      embedding in paraffin or epoxy resin. Transection and dicing of the tissue
      aggravated the untoward effects. In contrast, bubbles and films remained stable
      in either glutaraldehyde or formaldehyde, which, however, did not protect against
      the other agents. (2) Degassing destroyed all bubbles as expected; however,
      bubbles and films re-formed immediately with reinflation. (3) Topography of fixed
      bubbles and films was retained after air drying. The dry polygonal configuration
      reverted to spherical-oval either in saline solution or in 50% ethanol, whereas
      vulnerability to upgraded ethanol concentrations was unchanged. (4) Normal
      topography and shape appeared to be retained during quick freezing and after
      thawing. (5) Intraalveolar and intraductal bubbles and films were preserved and
      photographed in sections from tissue prepared by the double-impregnation
      procedure; they were not seen either when bubble formation had been blocked
      (double-impregnation procedure) or when preembedding in agar had been omitted.
      CONCLUSIONS: (1) Whether or not fixed in glutaraldehyde or formaldehyde,
      preservation of intraalveolar and intraductal bubbles and films is not to be
      expected in tissue prepared by conventional histopreparative procedures, whereas
      product artifacts may be expected from bubble rupture in situ. (2) Degassing
      cannot be recommended for studies of alveolar structure-function interrelations
      because all natural bubbles are disrupted in the process, and bubble re-formation
      may not parallel their "natural history" in vivo. (3) Compared with
      glutaraldehyde or formaldehyde fixation, air drying offers no added protection
      against the untoward effects of conventional processing. (4) Quick-frozen tissue
      is equally at risk. (5) A new double-impregnation procedure does preserve bubbles
      and films during processing, sectioning, and staining.

PMID- 9268141
TI  - SEM/TEM investigation of rat cardiac subcellular alterations induced by changing
      duration of noise stress.
AB  - BACKGROUND: Many studies have shown that loud noise is an environmental stressor.
      Noise exposure causes changes at different levels in living beings; the
      cardiovascular system, considered to be the most affected apparatus, has received
      much attention in both animals and humans. The present study investigated the
      effect of changing duration of noise stimulation on rat myocardium to determine
      whether the responses could be related to time. METHODS: The study was performed
      on young albino male rats. Three groups of animals were exposed to white noise
      (100 dBA) for 1, 6, and 12 hr, respectively, and samples of right atrium and
      ventricle were processed for ultrastructural examination. The subcellular
      organization of cardiomyocytes was examined by transmission and scanning electron
      microscopy, the latter being carried out with the modified osmium maceration
      method. RESULTS: After 1 hr of noise exposure, atrial and ventricular
      cardiomyocytes did not present significant alterations. After 6 hr, changes were
      observed in atrial tissue at the mitochondrial level, whereas the ventricular
      structure appeared unaffected. After 12 hr of treatment, in addition to the
      mitochondrial alterations, changes in atrial and ventricular myocardium,
      consisting of areas of enlargement in intercalated disc membranes and decreased
      density in sarcoplasm, were detected. CONCLUSIONS: The methods we applied for the
      visualization of cellular organelles allowed us to demonstrate that atrial tissue
      is primarily involved in stress response, especially at the mitochondrial level;
      a more prolonged time of exposure seems to be necessary for ventricular
      involvement.

PMID- 9268142
TI  - Factors influencing phagocytic response of macrophages from the sea bass
      (Dicentrarchus labrax L.): an ultrastructural and quantitative study.
AB  - BACKGROUND: Although phagocytosis is considered the main nonspecific defense
      mechanism in fish, the significance of the influence of bacterial properties and
      assay conditions on this mechanism has not been established. We report the
      influence of leukocyte source, bacterial species, presence or absence of a
      bacterial wall, bacterial status (live or dead), and bacterial opsonization on in
      vitro phagocytosis by sea bass (Dicentrarchus labrax L.) macrophages. METHODS:
      Leukocytes were challenged with bacteria under different conditions and
      ultrastructurally studied. The number of phagocytic macrophages and the number of
      bacteria ingested per macrophage were quantified by microscopical counting, and
      the data obtained were statistically analyzed following general linear models.
      RESULTS: Macrophages from sea bass peritoneal exudate showed a greater capacity
      to engulf bacteria than did those isolated from blood, which, in turn, had
      greater engulfment properties than did those isolated from head-kidney. Greater
      phagocytic activity was observed in the assays carried out with Escherichia coli
      than in those carried out with Salmonella typhimurium, especially when the TA1950
      S. typhimurium strain (with wall) was used. Macrophages showed greater phagocytic
      activity against live bacteria. Bacterial opsonization had a variable effect on
      phagocytosis. Sea bass macrophages did not always ingest the same number of
      bacteria. CONCLUSIONS: Sea bass macrophages have strong bacterial phagocytic
      activity. Significant differences were found that had been influenced by
      bacterial properties as well as by assay conditions. Positive correlation between
      the number of phagocytic macrophages and the number of bacteria ingested per
      phagocyte was observed.

PMID- 9268143
TI  - Ovine amniotic and allantoic epithelia across gestation.
AB  - BACKGROUND: Extensive studies on the regulation of the volume and composition of
      amniotic and allantoic fluid in the sheep have suggested that the amniotic and
      allantoic membranes must play an active role in these processes. Little is known
      of the functional morphology of the sheep amnion and allantois beyond the
      presence of an epithelium overlying connective tissue. METHODS: The ovine amnion
      and allantois were characterized at a range of gestational ages (27-140 days of
      gestation, where term is 145-150 days) by electron microscopy (SEM and TEM) and
      the presence of transporting ATPases examined by use of immunohistochemistry
      (Ca++-ATPase) and in situ hybridization (Na,K-ATPase). RESULTS: With increasing
      gestational age, the cell height of epithelium of the membranes increased, as did
      the number of apical microvilli and the length of zonulae occludentes. Epithelial
      cell cytoplasm increased in complexity, and cell shape changed from flattened to
      cuboidal. Proliferation of cells occurred until close to term. Immunoreactivity
      to Ca++-ATPase was present in the basolateral membranes at all stages of
      gestation examined, but hybridization with the alpha and beta subunits of Na,K
      ATPase was present only at or after 100 days of gestation. CONCLUSIONS: The
      epithelia of the sheep amnion and allantois display characteristics typical of
      transporting epithelia. As the epithelia mature, changes related to increased
      capacity for solute and fluid transport regulation occur.

PMID- 9268144
TI  - Central connections of the nucleus mesencephalicus nervi trigemini in the mallard
      (Anas platyrhynchos L.).
AB  - BACKGROUND: In the mallard duck, functionally distinct groups of jaw muscles are
      each innervated by a different subnucleus of the main trigeminal (mV) or facial
      (mVII) motor nucleus. The other subnuclei of mV and mVII innervate several head
      muscles, including lingual muscles. The reticular premotor cells of the
      trigeminal and facial jaw motor subnuclei occupy different areas in the
      parvocellular reticular formation (RPc). The cell bodies of jaw muscle spindle
      afferents are situated in the mesencephalic nucleus (MesV). In the present study,
      the central connections of MesV with jaw motor subnuclei and their premotor areas
      are investigated. METHODS: In a first series of experiments, horseradish
      peroxidase (HRP) injections were made in electrophysiologically identified
      trigeminal and facial subnuclei. In a second series of experiments, HRP was
      delivered iontophoretically at different parts of RPc. Anterograde tracing with
      tritiated leucine was used to confirm the central connections of MesV. Double
      labeling with fluorescent tracers was used to investigate whether MesV
      collaterals reach both the rostral and caudal parts of RPc. RESULTS: MesV
      projects to only two of the five different subnuclei of the trigeminal motor
      nucleus. The subnuclei that receive spindle afferents innervate jaw adductor
      muscles (mV2) or pro- and retractors of the mandible (pterygoid muscles; mV1).
      The three other subnuclei innervate jaw-opener muscles or other head muscles.
      MesV fibers also project to the rostral part of the dorsolateral RPc (RPcdl),
      which serves as a premotor area for the motor subnuclei of adductor and pterygoid
      muscles. The intermediate part of RPcdl does not contain premotor cells of mV or
      mVII, and a clear projection of MesV to this area is absent. The caudal part of
      RPcdl projects to the mV and mVII subnuclei that innervate jaw-opener muscles.
      This part of RPc receives a projection from the same MesV cells as the rostral
      RPcdl. The MesV projection to RPc does not include premotor cells of mV and mVII
      in the ventromedial part of RPc (RPcvm). CONCLUSIONS: Spindle afferents from jaw
      closer muscles project only to mV subnuclei innervating jaw-closer muscles (mV1,
      mV2) and to a population of premotor cells in the rostral RPcdl that innervates
      these subnuclei. The mixed population of premotor cells in RPcvm, which
      innervates both jaw-opener and jaw-closer subnuclei, does not receive a MesV
      projection. However, a premotor area for jaw-opener subnuclei in the caudal part
      of RPcdl does receive MesV input and may serve as a relay through which
      proprioceptive information from jaw closer spindles can reach jaw opener muscles.

PMID- 9268145
TI  - Identification of nerve endings in cat extraocular muscles.
AB  - BACKGROUND: The aim of the present study was to identify the varieties of sensory
      and motor nerve endings in cat extraocular muscles. METHODS: Sensory terminals
      were identify by injecting neuronal tracers (fast blue, biocytin, or peroxidase)
      into the trigeminal ganglion, which contains the sensory cells innervating the
      eye muscles. Motor terminals were identified by injections of horseradish
      peroxidase or DiI, a fluorescent carbocyanin dye, into either the oculomotor
      nerve or the IIIrd nuclei. RESULTS: Injections into the trigeminal ganglion
      anterogradely labelled three types of sensory nerve endings for each neuronal
      tracer used: (1) the well-known "palisade" endings at the myotendinous junction
      of each extraocular muscle; (2) "compact" endings consisting of a dense terminal
      arborization extending up to 60 microm in length on striated muscle fibres 10-15
      microm in diameter; and (3) "complex" endings on muscle fibres 15-20 microm in
      diameter. The complex ending issued from multiple collateral branches of the
      parent nerve fibre, which stretched and turned around the muscle fibre and gave
      off numerous terminal varicosities over a distance of about 140 microm. The
      sensory complex and compact endings presented strong similarities with some
      "atypical muscle spindles" previously described. In addition to the classic motor
      "plate" and "grape," we found evidence for the existence of motor "spiral"
      endings with each tracer. CONCLUSIONS: The sensory nature of the palisade endings
      was demonstrated, and two other types of sensory terminals were identified and
      described. The spiral nerve terminals were demonstrated to be motor in nature,
      and a possible function in the microsaccadic movements associated with fixation
      is suggested.

PMID- 9268146
TI  - Demonstration of nerve fibers containing the C-terminal flanking peptide of
      neuropeptide Y (CPON) in the pig pineal gland (Sus domesticus): an
      immunocytochemical study by light and electron microscopy.
AB  - BACKGROUND: The pineal gland is richly innervated by the neuropeptide Y (NPY)
      positive nerves that mostly exibit immunoreactivity for the enzyme tyrosine
      hydroxylase, a marker of sympathetic nerve fibers. NPY is synthesized as a part
      of larger prepromolecule. The present study was undertaken to demonstrate that
      the posttranslational processing of preproNPY resulted in the presence of C
      terminal flanking peptide of NPY (CPON) in nerve fibers of the pig pineal gland.
      METHODS: An immunohistochemical anti-CPON technique was done over mounted
      sections of perfusion-paraformaldehyde-fixed material. An immunocytochemical
      preembedding technique was done to study the CPON-positive nerve terminals under
      electron microscopy. RESULTS: The pig pineal gland is densely innervated by CPON
      immunoreactive nerve fibers. These nerve fibers follow from the pineal capsule
      into the connective tissue septa and farther into the pineal parenchyma, where
      the varicose branches terminate between the pinealocytes. The fiber density was
      the highest in the peripheral and ventral parts of the gland. At the
      ultrastructural level, the CPON-immunoreactive nerve terminals were found in the
      perivascular spaces and in the parenchyma. The terminals contained small vesicles
      (30-40 nm in diameter), some of which showed an eccentrically located dense core.
      In addition, large clear vesicles (80-100 nm in diameter) were present. Some of
      the CPON-immunoreactive nerve terminals were found in close apposition to the
      pinealocyte cell membrane, making a synapticlike contact with the pinealocytes.
      CONCLUSIONS: Our results show the presence of dense CPON-IR innervation in the
      pig pineal gland. The ultrastructural localization of CPON-IR nerve terminals
      shows that the peptide can be released to both perivascular and intercellular
      spaces. The functional role for this peptide in pig pineal gland is still an open
      question.

PMID- 9268147
TI  - External marker-based automatic congruencing: a new method of 3D reconstruction
      from serial sections.
AB  - BACKGROUND: Computer-based three-dimensional (3D) visualizations reconstructed
      from sectional images represent a valuable tool in biomedical research and
      medical diagnosis. Particularly with those imaging techniques that provide
      virtual sections, such as CT, MRI, and CLSM, 3D reconstructions have become
      routine. Reconstructions from physical sections, such as those used in
      histological preparations, have not experienced an equivalent breakthrough, due
      to inherent shortcomings in sectional preparation that impede automated image
      processing and reconstruction. The increased use of molecular techniques in
      morphological research, however, generates an overwhelming amount of 3D molecular
      information, stored within series of physical sections. This valuable information
      can be fully appreciated and interpreted only through an adequate method of 3D
      visualization. METHODS AND RESULTS: In this paper we present a new method for a
      reliable and largely automated 3D reconstruction from physically sectioned
      material. The 'EMAC' concept (External Marker-based Automatic Congruencing)
      successfully approaches the three major obstacles to automated 3D reconstruction
      from serial physical sections: misalignment, distortion, and staining variation.
      It utilizes the objectivity of external markers for realignment of the sectional
      images and for geometric correction of distortion. A self-adapting dynamic
      thresholding technique compensates for artifactual staining variation and
      automatically selects the desired object contours. CONCLUSIONS: Implemented on a
      low-cost hardware platform, EMAC provides a fast and efficient tool that largely
      facilitates the use of computer-based 3D visualization for the analysis of
      complex structural, molecular, and genetic information in morphological research.
      Due to its conceptual versatility, EMAC can be easily adapted for a broad range
      of tasks, including all modern molecular-staining techniques, such as
      immunohistochemistry and in situ hybridization.

PMID- 9268148
TI  - How viruses escape from cytotoxic T lymphocytes: molecular parameters and
      players.
AB  - Viruses that persist in infected hosts must evolve successful strategies to avoid
      recognition by the immune system. The primary player in antiviral immune
      surveillance is the CD8+ cytotoxic T lymphocyte (CTL), and the battle drawn
      between the CTLs and viruses is the focus of this review. In this struggle,
      viruses can follow multiple distinct pathways. For example, DNA viruses often
      adopt the strategy of encoding proteins that interfere with the immune response
      along routes of antigen presentation. Such interference prevents the viral
      peptide from binding to the major histocompatibility complex (MHC) class I
      glycoprotein; therefore, no virus-MHC complex forms for recognition by antiviral
      CTLs. RNA viruses, having fewer genes, generate swarms of quasispecies that can
      contain mutated viral proteins. When such mutants occur in viral peptides
      presented to the MHC protein or the residue recognized by the CTL receptor, CTL
      recognition and activation fail. If, instead, the mutation occurs in the viral
      peptide flanking sequence, the infected cell may not process the viral peptide
      from the cytosol to the endoplasmic reticulum. Viruses can also directly or
      indirectly attack dendritic cells and CD4+ or CD8+ T lymphocytes, other routes
      that interfere with immune functions. Dendritic cells are the primary
      professional antigen-presenting cells and are critical for the activation of CTL
      responses. CD4+ T lymphocytes provide help for long-term CD8+ CTL activity and
      are necessary for its maintenance. Consequently, interference with either
      dendritic or CD4+ cell types constitutes yet another way that viruses can disable
      the immune response and persistently infect their host.

PMID- 9268149
TI  - Disruption of the varicella-zoster virus dUTPase and the adjacent ORF9A gene
      results in impaired growth and reduced syncytia formation in vitro.
AB  - Varicella-zoster virus (VZV) open reading frame 8 (ORF8) is predicted to encode
      the viral dUTPase and the adjacent gene, ORF9A, is thought to encode a membrane
      protein homologous to HSV-1 UL49.5. A fusion protein, in which the amino portion
      of glutathione-S-transferase was fused to amino acids 5 to 396 of VZV ORF8
      protein, had dUTPase activity in vitro. Construction of a mutant VZV with stop
      codons or a deletion in the ORF8 gene resulted in loss of viral dUTPase activity.
      Antibody to VZV ORF9A protein demonstrated a 7-kDa protein located in the
      membranes of virus-infected cells. Insertion of stop codons into VZV ORF9A
      resulted in VZV that produced smaller plaques than parental virus. Inactivation
      of both VZV ORF8 and ORF9A resulted in a virus that grew to lower titers and was
      impaired for syncytia formation when compared to parental virus. In contrast, a
      similar mutation in HSV-1 has no effect on growth of the virus in vitro. These
      results identify loci in the VZV genome that are required for a syncytial
      phenotype in vitro.

PMID- 9268150
TI  - Mutant CD4 molecules with improved binding to HIV envelope protein gp120 selected
      by phage display.
AB  - Phage-display methodology has been used to select variant CD4 proteins exhibiting
      increased binding to the surface envelope glycoprotein, gp120, of Human
      Immunodeficiency Virus Type-1. To facilitate the selection, a library of mutant
      CD4 proteins was constructed by cloning a PCR-generated error prone population of
      the first two domains of CD4 into the phagemid expression vector pHEN1. Phage
      displaying CD4 in functional form were confirmed by Western blot with CD4
      specific antibody and by phage ELISA on immobilized gp120. Biopanning of CD4
      phage on immobilized gp120 followed by individual characterization identified
      five clones with increased binding to gp120. All of the selected variants had one
      or two amino acid substitutions within the V1 domain of CD4, notably at positions
      15, 27, 30, 50, and 66 located in the strands surrounding the main binding loop.
      Variants which exhibited increased binding to recombinant gp120 in vitro were
      also shown to have an increased capacity for virus neutralization broadly in line
      with their in vitro binding activity.

PMID- 9268151
TI  - Mutational analyses support a model for the HRV2 2A proteinase.
AB  - The proteinase 2A of human rhinovirus 2 is a cysteine proteinase which contains a
      tightly bound Zn ion thought to be required for structural integrity. A three
      dimensional model for human rhinovirus type 2 proteinase 2A (HRV2 2A) was
      established using sequence alignments with small trypsin-like Ser-proteinases
      and, for certain regions, elastase. The model was tested by expressing selected
      proteinase 2A mutants in bacteria and examining the effect on both intramolecular
      ("cis") and intermolecular ("trans") activities. The HRV2 proteinase 2A is
      proposed to have a two domain structure, with the catalytic site and substrate
      binding region on one face of the molecule and a Zn-binding motif on the opposite
      face. Residues Gly 123, Gly 124, Thr 121, and Cys 101 are proposed to be involved
      in the architecture of the substrate binding pocket and to provide the correct
      environment for the catalytic triad of His 18, Asp 35, and Cys 106. Residues Tyr
      85 and Tyr 86 are thought to participate in substrate recognition. The presence
      of an extensive C-terminal helix, in which Asp 132, Arg 134, Phe 130, and Phe 136
      play important roles, explains why mutations in this region are generally
      detrimental to proteinase activity. The proposed Zn-binding motif comprises Cys
      52, Cys 54, Cys 112, and His 114. Exchange of these residues inactivates the
      enzyme. Furthermore, as measured by atom emission spectroscopy, Zn was absent
      from purified preparations of proteinase 2A in which His 114 had been replaced by
      Asn. The absence of disulphide bridges was confirmed by subjecting highly
      purified HRV2 proteinase 2A to one- and two-step alkylation procedures.

PMID- 9268152
TI  - Intravirion generation of the C-terminal core domain of HIV-1 Nef by the HIV-1
      protease is insufficient to enhance viral infectivity.
AB  - Wild-type HIV-1 is more infectious than nef-deleted HIV-1 in both limiting
      dilution and single-cycle infectivity assays. Moreover, Nef expression from a
      separate plasmid in the virus-producing cells is capable of restoring the
      infectivity of genetically nef-deficient HIV-1. These observations indicate that
      the virion itself is altered by Nef expression to promote viral infectivity.
      Sucrose gradient-purified HIV-1 virions contain full-length Nef protein and its
      inclusion is dependent on N-terminal myristylation of Nef. As myristylation
      defective mutants of Nef do not enhance infectivity, incorporation of Nef into
      virions may mediate the enhanced infectivity. Studies with recombinant Nef have
      further shown that HIV-1 protease can cleave Nef into two polypeptides, a 20-kDa
      C-terminal core domain and a small N-terminal domain. Our analysis of purified
      HIV-1 virions also showed a 20-kDa form of Nef. The generation of this 20-kDa
      form of Nef was inhibited by an HIV-1 protease inhibitor, and its C-terminal core
      domain identity was confirmed through epitope-tagging. Immunoblots of virions
      demonstrated that 60-80% of the incorporated Nef is cleaved by the HIV-1
      protease. This finding raised the possibility that the Nef core domain, which may
      no longer be tethered to the membrane due to absence of an N-terminal myristyl
      anchor, might mediate the enhanced infectivity. Therefore, a panel of mutants
      surrounding the proteolytic cleavage site in Nef were analyzed for effects on
      cleavage and enhancement of viral infectivity. Although some Nef mutants both
      failed to cleave and did not enhance viral infectivity, other mutants proved
      discordant in these functions. Specifically, two mutants that contained point
      mutations in the N-terminal domain cleaved normally, hence generating wild-type
      Nef core domain, yet failed to enhance infectivity. Thus, although the majority
      of the Nef protein in HIV-1 virions is cleaved by the viral protease into a 20
      kDa C-terminal core domain, generation of this core domain of Nef appears
      insufficient to enhance HIV-1 infectivity. These findings suggest that protease
      cleavage of the Nef protein in virions is irrelevant for the infectivity function
      of Nef.

PMID- 9268153
TI  - Infected cell protein 22 of herpes simplex virus 1 regulates the expression of
      virion host shutoff gene U(L)41.
AB  - The U(L)41 protein of herpes simplex virus 1 (HSV-1) is packaged into virions,
      and in newly infected cells the protein mediates indiscriminate degradation of
      mRNA, which causes a shutoff of protein synthesis. We report that in cells
      infected with mutant virus in which either alpha22/U(S)1.5 or U(L)13 had been
      deleted: (i) the shutoff of protein synthesis and the degradation of mRNA did not
      take place or were greatly reduced, and consistent with these observations (ii)
      cells infected with mutant viruses accumulated less U(L)41 mRNA and protein than
      cells infected with the parent virus; and (iii) purified virions from cells
      infected with deltaU(L)13 or delta alpha22/deltaU(S)1.5 viruses contained less
      U(L)41 protein than virions produced by the wild-type parent virus. We conclude
      that the failure of the U(L)13- mutant virus to shut off protein synthesis
      immediately after infection is due to the failure of posttranslational
      modification of infected cell protein 22 and/or the related U(S)1.5 protein by
      the U(L)13 protein kinase. The regulatory effect of U(L)13 on U(L)41 is indirect
      and not contingent on direct interaction of this protein with the U(L)41 protein.

PMID- 9268154
TI  - The large subunit of herpes simplex virus type 2 ribonucleotide reductase (ICP10)
      is associated with the virion tegument and has PK activity.
AB  - The large subunit of herpes simplex virus type 2 (HSV-2) ribonucleotide reductase
      (ICP10) was identified in sucrose gradient-purified HSV-2 virions by
      immunoprecipitation/immunoblotting with antibody specific for the protein kinase
      (PK) domain. Immunoblotting of individual gradient fractions indicated that ICP10
      cosediments with the major capsid protein and the highest virus titers. ICP10 was
      not labeled by iodination of purified virions, indicating that it is not located
      on the virion surface. After envelope glycoproteins were removed by detergent
      treatment, ICP10 was associated with capsid-tegument particles and became
      sensitive to trypsin digestion. The capsid-tegument-associated ICP10 was
      phosphorylated and had PK activity in vitro and on Immobilon membranes. A mutant
      ICP10 protein deleted in the PK domain (p95) was also associated with purified
      virions (ICP10deltaPK virus) but it lacked PK activity. The data indicate that
      ICP10 is contained within the tegument component where it retains intrinsic PK
      activity.

PMID- 9268155
TI  - Suppression of potyvirus infection by coexpressed closterovirus protein.
AB  - A tobacco etch virus (TEV)-based expression vector has been used for insertion of
      several ORFs derived from the unrelated beet yellows virus (BYV). Hybrid TEV
      variants expressing the BYV capsid protein, 20-kDa protein, or HSP70 homolog
      systemically infected Nicotiana tabacum and stably retained BYV sequences. In
      contrast, insertion of the ORF encoding BYV leader proteinase (L-Pro) resulted in
      severely impaired systemic transport and accumulation of recombinant TEV. Progeny
      of this virus underwent various deletions affecting the L-Pro sequence and
      mitigating the defects in virus spread. Model experiments involving several
      spontaneous and engineered mutants indicated that the central domain of BYV L-Pro
      was responsible for the defect in hybrid virus accumulation, whereas full-size L
      Pro was required for maximal debilitation of systemic transport. Strikingly, BYV
      L-Pro expression did not debilitate systemic infection of hybrid TEV in Nicotiana
      benthamiana plants. No major defects in replication or encapsidation of
      recombinant RNA were revealed in N. tabacum protoplasts. These results indicated
      that BYV L-Pro specifically interfered with TEV systemic transport and
      accumulation in a host-dependent manner and suggested a potential utility of
      closterovirus L-Pro as an inhibitor of potyvirus infection. In addition, it was
      demonstrated that the 107-amino-acid-residues-long N-terminal part of the TEV
      helper component proteinase is not essential for systemic infection.

PMID- 9268156
TI  - Identification of cis-acting repressor activity within human immunodeficiency
      virus type 1 protease sequences.
AB  - Human immunodeficiency virus type-1 (HIV-1) Rev overcomes negative elements
      within viral RNAs to allow expression of gag, pol, and env. The effect of Rev on
      protein and RNA expression of HIV-1 protease (PR)-containing constructs was
      investigated utilizing transient transfection of COS cells. Rev, through the Rev
      response element (RRE), resulted in a large increase in proteolytic activity and
      cytoplasmic RNA accumulation. Furthermore, Rev increased the level of total RNA
      produced by a PR-containing construct. The increase in cytoplasmic RNA
      accumulation in the presence of Rev indicated the presence of cis-acting
      repressor sequences (CRS) within the RNA produced by this construct. Therefore,
      components of the construct were analyzed for CRS activity. PR sequences in both
      sense and antisense orientations exhibited CRS activity. RRE sequences alone
      conferred a small CRS effect. Additional CRS activity was present within an
      unspliced RNA containing only nef and LTR sequences. These results indicate a
      novel form of cis-acting repressor activity within HIV-1 PR; this activity is
      exerted regardless of the orientation of PR and appears to function at the level
      of cytoplasmic or nuclear RNA stability.

PMID- 9268157
TI  - A peptide encoding a B-cell epitope from the N-terminus of the capsid protein L2
      of bovine papillomavirus-4 prevents disease.
AB  - The first 200 N-terminus amino acids of the L2 capsid protein of BPV-4
      (designated L2a) are an effective prophylactic vaccine against BPV-4 infection.
      Vaccination with L2a induces the production of virus neutralizing antibodies, and
      when L2a antibodies are removed from immune sera, the sera lose their
      neutralization activity. L2a encodes three dominant B-cell epitopes, defined as
      epitope 1 (amino acids 101-120), epitope 2 (aa 131-151), and epitope 3 (aa 151
      170). To investigate whether any of these epitopes are responsible individually
      or in combination for protection against viral challenge, synthetic peptides,
      corresponding to the three epitopes (peptides 11, 14, and 16, respectively) and
      conjugated to keyhole limpet hemocyanin (KLH) were tested in vaccination
      challenge experiments. Calves vaccinated with the three peptides together showed
      no evidence of papillomavirus infection; those vaccinated with peptide 14 alone
      developed only early lesions which did not progress to proper papillomas and
      regressed rapidly; those vaccinated with peptide 11 or peptide 16 alone were not
      protected and proceeded to develop papillomas. Therefore the three B-cell
      epitopes are not conventionally "neutralizing" when presented individually, but
      in combination they form a complex neutralization domain, and, in particular,
      epitope 2, represented by peptide 14, encodes a domain responsible for disease
      prevention.

PMID- 9268158
TI  - Reciprocal regulation of the early promoter region of bacteriophage HP1 by the
      Cox and Cl proteins.
AB  - We have identified a transcriptional switch at the early promoter region of
      bacteriophage HP1. This switch controls the transcription of the early lytic
      operon from the P(R1) and P(R2) promoters and the transcription of the lysogenic
      operon from the P(L) promoter. The start sites of the three promoters were
      mapped, and using a chloramphenicol acetyl transferase assay, we have
      investigated the levels of transcription from the promoters in the absence or in
      the presence of two phage-encoded transcription factors: HP1 Cox and HP1 Cl. The
      HP1 Cox protein repressed the production of P(L) transcripts 30-fold, while the
      HP1 Cl protein repressed lytic transcription at least 70-fold. Binding sites for
      HP1 Cox and Cl were identified in the early promoter region; mutations of these
      sites eliminated transcriptional repression. In addition, a mutant Cl protein was
      isolated which is temperature sensitive for repression. Taken together, these
      data demonstrate the reciprocal regulation of a transcriptional switch in which
      the actions of the two phage-encoded proteins at the phage early promoters
      determine the choice between lytic and lysogenic growth.

PMID- 9268159
TI  - Selective inhibition of l kappaB alpha phosphorylation and HIV-1 LTR-directed
      gene expression by novel antioxidant compounds.
AB  - Oxidative stress activates the NF-kappaB/Rel transcription factors which are
      involved in the activation of numerous immunoregulatory genes and the human
      immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR). In the present
      study, we examined the effects of established and novel compounds including
      antioxidants, ribonucleotide reductase inhibitors, and iron chelators on NF
      kappaB activation and HIV LTR-mediated gene expression induced by TNF-alpha. N
      Acetylcysteine (NAC), pyrrolidinedithiocarbamate (PDTC), and Trimidox (TD) at
      various concentrations inhibited TNF-alpha-induced NF-kappaB binding in Jurkat
      cells. Pretreatment of cells with these compounds prior to stimulation prevented
      I kappaB alpha degradation. Phosphorylation of I kappaB alpha, a prerequisite for
      its signal-induced degradation, was abrogated in these cells, indicating that
      oxidative stress is an essential step in the NF-kappaB activation pathway. On the
      other hand, iron chelators desferrioxamine, pyridoxal isonicotinoyl hydrazone
      (PIH), and salicylaldehyde isonicotinoyl hydrazone (SIH) showed no inhibition of
      TNF-alpha-induced NF-kappaB DNA-binding activity. Synergistic induction of HIV-1
      LTR-mediated gene expression by TNF-alpha and the HIV-1 transactivator Tat in
      Jurkat cells was significantly suppressed in the presence of NAC and TD, but not
      PDTC. The inhibition of NAC and TD on LTR-directed gene expression was diminished
      when NF-kappaB-binding sites in the LTR were deleted, indicating that these
      compounds affected the NF-kappaB component of the synergism. Iron chelators PIH
      and SIH also showed some inhibitory effect on LTR-mediated gene activation,
      presumably through an NF-kappaB-independent mechanism. These experiments
      demonstrate that TD, at concentration 50 times lower than the effective
      concentration of NAC, potently inhibits NF-kappaB activity and suppresses HIV LTR
      expression.

PMID- 9268160
TI  - In vivo selection of duck hepatitis B virus pre-S variants which escape from
      neutralization.
AB  - To better understand the role of specific residues within the duck hepatitis B
      virus (DHBV) pre-S protein in neutralization and infectivity, we have selected
      and identified pre-S variants which escape neutralization. A highly neutralizing
      monoclonal antibody (Mab 900) which recognizes an epitope 83IPQPQWTP90 localized
      previously on the DHBV pre-S protein, within a region suspected to mediate the
      virus interaction with hepatocytes, was used as immune pressure. After only two
      in vivo neutralization rounds with Mab 900, five different pre-S mutant genomes
      were identified, which harbored point mutations affecting only proline residues
      located at position 90 within this epitope (83IPQPQWTP90) and/or at a distance at
      position 5. We have shown that a single (P5L) or double proline (P5L + P90H)
      substitution affect neither virus replication capacity nor in vivo infectivity.
      However, the P5 mutation reduces mutant recognition by Mab 900 twofold, while the
      substitution of both prolines 5 and 90 almost completely abolishes mutant P5L +
      P90H reactivity with this Mab and leads to a decrease of neutralization.
      Therefore we describe here an experimental system which allows rapid in vivo
      selection and identification of DHBV pre-S variants and provide evidence that
      residues within and at a distance from the neutralization epitope are important
      in DHBV neutralization but do not affect its replication capacity and
      infectivity.

PMID- 9268161
TI  - The genome-linked protein of potato leafroll virus is located downstream of the
      putative protease domain of the ORF1 product.
AB  - The sequence of the 32 N-terminal amino acids of the protein (VPg) which is
      covalently linked to the RNA of potato leafroll virus has been determined. The
      obtained VPg sequence mapped to position 400 to 431 of the PLRV ORF1 product,
      downstream of the putative protease domain and in front of the RNA-dependent RNA
      polymerase. Comparison with other viral sequences revealed significant
      similarities with the ORF1 products of beet western yellows virus, cucurbit aphid
      borne yellows virus, and beet mild yellowing virus.

PMID- 9268162
TI  - Type 1 HERV-K genome is spliced into subgenomic transcripts in the human breast
      tumor cell line T47D.
AB  - Two types of HERV-K genomes exist which differ in the absence (type 1) or the
      presence (type 2) of a sequence of 292 nucleotides between the putative pol and
      env genes. Previously published results from teratocarcinoma cell studies had
      firmly concluded that the type 1 HERV-K genome was defective in splicing and that
      only the nondeleted type 2 HERV-K genome containing the 292-nucleotide sequence
      was capable of being spliced. We now show that in the T47D human breast tumor
      cell line it is the type 1 HERV-K genome, and not the type 2, which is spliced to
      subgenomic transcripts.

PMID- 9268163
TI  - Evidence for induction of interferon-alpha and interferon-beta in retinal glial
      cells of Muller.
AB  - Studies were performed to determine if retinal glial cells of Muller transcribe
      the genes for interferon-alpha (IFNalpha) or IFNbeta upon exposure to virus.
      Responses to herpes simplex virus type 1 (HSV-1) were tested with cultured murine
      Muller cells and, in vivo, with retinas obtained after bilateral injection of
      either HSV-1 or buffer into the anterior chamber of the eyes of BALB/c mice.
      Induction of IFN transcription and relative temporal changes in transcript levels
      occurred over time after either in vitro or in vivo exposure to HSV-1.
      Transcription of both IFN genes was induced in cultured glia within 1 hr after
      exposure to virus. IFN transcripts were detected in retinas by 24 hr
      postinfection and these were maximal at 3 days. By in situ hybridization (ISH),
      IFNalpha2 mRNA localized to focal areas in the intact retinas of virus-injected
      eyes and was consistent with our previous report of a transient, focal appearance
      of viral antigens in those retinas. Uninfected cells and ocular tissues were
      negative for IFN transcripts. Combined ISH and immunohistochemistry on retinal
      impression smears confirmed that glial fibrillary acidic protein-positive Muller
      cells are an intraretinal source of IFNalpha and IFNbeta transcripts after ocular
      exposure to HSV-1. Our results support a role for Muller cells as participants in
      intraretinal antiviral or immunomodulatory responses via type 1 IFN production
      and may have implications for future therapeutic interventions.

PMID- 9268164
TI  - Mapping and expression of southern bean mosaic virus genomic and subgenomic RNAs.
AB  - The coat protein of the cowpea strain of southern bean mosaic sobemovirus (SBMV
      C) is translated from a subgenomic RNA (sgRNA) that is synthesized in the virus
      infected cell. Like the SBMV-C genomic RNA, the sgRNA has a viral protein (VPg)
      covalently bound to its 5' end. The mechanism(s) by which ribosomes initiate
      translation on the SBMV-C RNAs is not known. To begin to characterize the
      translation of the sgRNA it was first necessary to precisely map its 5' end.
      Primer extension was used to identify SBMV-C nucleotide (nt) 3241 as the
      transcription start site. As a control, the 5' end of the genomic RNA was also
      mapped. Surprisingly, the 5' terminal nt of this RNA was identified as SBMV-C nt
      2. The primary structure of the 5' ends of these two RNAs is therefore expected
      to be VPg-ACAAAA. Precise mapping of the 5' end of the sgRNA of the bean strain
      of SBMV (SBMV-B) demonstrated that it has these same elements. Translation of
      coat protein from the SBMV-C sgRNA and p21 from the SBMV-C genomic RNA was
      compared using a cell-free system. The results of these experiments were
      consistent with translation of these proteins by a 5' end-dependent scanning
      mechanism rather than by internal ribosome binding.

PMID- 9268165
TI  - Infected macaques that controlled replication of SIVmac or nonpathogenic SHIV
      developed sterilizing resistance against pathogenic SHIV(KU-1).
AB  - Twenty macaques were used to evaluate the ability of nonpathogenic SIV(mac) or
      nonpathogenic chimeric SIV-HIV (SHIV) to induce protection in macaques against
      superinfection with a pathogenic variant of SHIV (SHIV(KU-1)) originally
      containing the tat, rev, vpu, and env of HIV-1 (strain HXB2) in a genetic
      background of SIV(mac)239. Specifically, three macaques inoculated with
      molecularly cloned, macrophage-tropic SIV(mac)LG1 developed an early systemic
      infection but recovered with only traces of SIV(mac) DNA in visceral lymphoid
      tissues. These animals were then inoculated parenterally with pathogenic SHIV(KU
      1). All three animals resisted infection with SHIV(KU-1), as indicated by lack of
      virus recovery and absence of SHIV-specific env and vpu sequences in the visceral
      lymphoid tissues and multiple regions in the CNS. We also examined the ability of
      five macaques that had been inoculated with nonpathogenic SHIV (NP-SHIV) to
      withstand challenge with the pathogenic SHIV(KU-1). Like the SIV(mac)LG1
      inoculated macaques, these animals also resisted SHIV(KU-1) challenge as judged
      by the inability to recover infectious virus, normal CD4+ T cell counts, and the
      absence of SHIV(KU-1) signature sequences in the lymph node tissue. Thus, eight
      of eight animals that developed control over primary lentivirus infections had
      also developed resistance to infection with pathogenic SHIV(KU-1). Three groups
      of macaques were used as controls for this study. The first group consisted of
      six macaques inoculated with SHIV(KU-1) alone. All animals developed viremia,
      showed severe loss of CD4+ T cells within 4 weeks, and succumbed to AIDS within 6
      months. The second group of three macaques was inoculated first with SHIV(KU-1)
      and inoculated later with uncloned, neurovirulent SIV(mac)7F-Lu. A third group of
      three macaques was inoculated with SIV(mac)7F-Lu followed by inoculation with
      SHIV(KU-1). PCR analyses using oligonucleotide primers specific for the SIV or
      HIV env revealed that macaques from the last two groups had widespread infection
      with both SHIV(KU-1) and SIV(mac), indicating that animals that failed to control
      productive replication of either SHIV(KU-1) or SIV(mac)7F-Lu could not resist
      superinfection with the other virus. These data indicate that sterilizing
      immunity against the virulent SHIV could be induced in animals that had
      experienced an immunizing infection. Moreover, the divergence of the envelope
      glycoprotein of the protective avirulent and virulent challenge virus suggests
      that a single vaccine could protect against infection with a virus containing a
      different envelope glycoprotein.

PMID- 9268166
TI  - HIV-1 coreceptor activity of CCR5 and its inhibition by chemokines: independence
      from G protein signaling and importance of coreceptor downmodulation.
AB  - HIV-1 infection requires the presence of specific chemokine receptors on CD4+
      target cells to enable the fusion reactions involved in virus entry. CCR5 is a
      major fusion coreceptor for macrophage-tropic HIV-1 isolates. HIV-1 entry and
      fusion are mediated by the viral envelope glycoprotein (Env) and are inhibited by
      CCR5 ligands, but the mechanisms are unknown. Here, we test the role of G protein
      signaling and CCR5 surface downmodulation by two separate approaches: direct
      inactivation of CCR5 signaling by mutagenesis and inactivation of G(i)-type G
      proteins with pertussis toxin. A CCR5 mutant lacking the last 45 amino acids of
      the cytoplasmic C-terminus (CCR5306) was created that was expressed on
      transfected cells at levels comparable to cells expressing CCR5 and displayed
      normal chemokine binding affinity. CCR5 ligands induced calcium flux and receptor
      downmodulation in cells expressing CCR5, but not in cells expressing CCR5306.
      Nevertheless, CCR5 or CCR5306, when coexpressed with CD4, supported comparable
      HIV-1 Env-mediated cell fusion. Consistent with this, treatment of CCR5
      expressing cells with pertussis toxin completely blocked ligand-induced transient
      calcium flux, but did not affect Env-mediated cell fusion or HIV-1 infection.
      Also, pertussis toxin did not block chemokine inhibition of Env-mediated cell
      fusion or HIV-1 infection. However, chemokines inhibited Env-mediated cell fusion
      less efficiently for CCR5306 than for CCR5. We conclude that the C-terminal
      domain of CCR5 is critical for G protein signaling and receptor downmodulation
      from the surface, but that neither function is required for CCR5 fusion
      coreceptor activity. The contrasting phenotypes of CCR5 and CCR5306 suggest that
      coreceptor downmodulation and direct blockage of Env interaction sites both
      contribute to chemokine inhibition of HIV-1 infection.

PMID- 9268167
TI  - Persistence and evolution of feline coronavirus in a closed cat-breeding colony.
AB  - Feline coronavirus (FCoV) persistence and evolution were studied in a closed cat
      breeding facility with an endemic serotype I FCoV infection. Viral RNA was
      detected by reverse transcriptase polymerase chain reaction (RT-PCR) in the feces
      and/or plasma of 36 of 42 cats (86%) tested. Of 5 cats, identified as FCoV
      shedders during the initial survey, 4 had detectable viral RNA in the feces when
      tested 111 days later. To determine whether this was due to continuous
      reinfection or to viral persistence, 2 cats were placed in strict isolation and
      virus shedding in the feces was monitored every 2-4 days. In 1 of the cats, virus
      shedding continued for up to 7 months. The other animal was sacrificed after 124
      days of continuous virus shedding in order to identify the sites of viral
      replication. Viral mRNA was detected only in the ileum, colon, and rectum. Also
      in these tissues, FCoV-infected cells were identified by immunohistochemistry.
      These findings provide the first formal evidence that FCoV causes chronic enteric
      infections. To assess FCoV heterogeneity in the breeding facility and to study
      viral evolution during chronic infection, FCoV quasispecies sampled from
      individual cats were characterized by RT-PCR amplification of selected regions of
      the viral genome followed by sequence analysis. Phylogenetic comparison of
      nucleotides 7-146 of ORF7b to corresponding sequences obtained for independent
      European and American isolates indicated that the viruses in the breeding
      facility form a clade and are likely to have originated from a single founder
      infection. Comparative consensus sequence analysis of the more variable region
      formed by residues 79-478 of the S gene revealed that each cat harbored a
      distinct FCoV quasispecies. Moreover, FCoV appeared to be subject to immune
      selection during chronic infection. The combined data support a model in which
      the endemic infection is maintained by chronically infected carriers. Virtually
      every cat born to the breeding facility becomes infected, indicating that FCoV is
      spread very efficiently. FCoV-infected cats, however, appear to resist
      superinfection by closely related FCoVs.

PMID- 9268168
TI  - Double-stranded RNA-dependent protein kinase (PKR) is regulated by reovirus
      structural proteins.
AB  - Reovirus sigma3 is a virion outer shell protein that also binds dsRNA and
      stimulates translation by blocking activation of the dsRNA-dependent protein
      kinase, PKR. Purified sigma3 was shown by gel shift assay to bind specifically to
      RNA duplexes of minimal length 32-45 base pairs. PKR binding to dsRNA was
      prevented by sigma3, and translation inhibition of luciferase reporter by PKR
      expression in transfected cells was reversed by sigma3. Association of sigma3
      with its outer capsid partner mu1/mu1C eliminated dsRNA binding and prevented
      restoration of protein synthesis. Analyses of sigma3 mutants demonstrated a
      direct correlation between dsRNA binding and reversal of the down-regulation of
      translation by PKR. In infected cells, sigma3 was stable but dsRNA binding
      decreased, presumably due to mu1/mu1C complex formation. The results suggest a
      functional transition from early inhibition of PKR activation by sigma3 to its
      association with mu1/mu1C in capsid structures.

PMID- 9268169
TI  - A highly conserved DNA replication module from Streptococcus thermophilus phages
      is similar in sequence and topology to a module from Lactococcus lactis phages.
AB  - A highly conserved DNA region extending over 5 kb was observed in Streptococcus
      thermophilus bacteriophages. Comparative sequencing of one temperate and 26
      virulent phages demonstrated in the most extreme case an 18% aa difference for a
      predicted protein, while the majority of the phages showed fewer, if any aa
      changes. The relative degree of aa conservation was not homogeneous over the DNA
      segment investigated. Sequence analysis of the conserved segment revealed genes
      possibly involved in DNA transactions. Three predicted proteins (orf 233, 443,
      and 382 gene product (gp)) showed nucleoside triphosphate binding motifs. Orf 443
      gp showed in addition a DEAH box motif, characteristically found in a subgroup of
      helicases, and a variant zinc finger motif known from a phage T7
      helicase/primase. Tree analysis classified orf 443 gp as a distant member of the
      helicase superfamily. Orf 382 gp showed similarity to putative plasmid DNA
      primases. Downstream of orf 382 a noncoding repeat region was identified that
      showed similarity to a putative minus origin from a cryptic S. thermophilus
      plasmid. Four predicted proteins showed not only high degrees of aa identity (34
      to 63%) with proteins from Lactococcus lactis phages, but their genes showed a
      similar topological organization. We interpret this as evidence for a horizontal
      gene transfer event between phages of the two bacterial genera in the distant
      past.

PMID- 9268170
TI  - Recognition of dengue virus NS1-NS2a proteins by human CD4+ cytotoxic T
      lymphocyte clones.
AB  - We examined nine dengue virus-specific human CD4+ CD8- cytotoxic T lymphocyte
      (CTL) clones for protein recognition, using recombinant vaccinia viruses which
      contain genes coding for dengue virus proteins. These clones were established
      from peripheral blood mononuclear cells of a donor previously immunized with a
      live-attenuated experimental dengue-1 vaccine. Of nine CD4+ T cell clones, seven
      were dengue-1-specific and two were dengue-1-dengue-3 cross-reactive. Four dengue
      1-specific clones and one dengue-1-dengue-3 cross-reactive clone recognized
      epitopes within the NS1 or NS2a proteins. Analysis of human leukocyte antigen
      (HLA) restriction revealed that three dengue-1-specific clones are HLA-DR1
      restricted and one dengue-1-dengue-3 cross-reactive clone is HLA-DPw3-restricted.
      These results indicate that NS1 and NS2a proteins as well as C, E, and NS3
      proteins reported earlier contain one or more epitopes recognized by dengue virus
      specific human CD4+ T lymphocytes.

PMID- 9268171
TI  - Warfarin and heparin-induced skin necrosis and the purple toe syndrome:
      infrequent complications of anticoagulant treatment.

PMID- 9268172
TI  - In vivo photoactivation of caged-thrombin.
AB  - Aberrant ocular neovascularization is a major cause of blindness in the world.
      Abnormal blood vessels in the eye may produce corneal opacification, corneal
      transplant rejection, neovascular glaucoma, vitreous hemorrhage, traction retinal
      detachment, and subretinal scars from choroidal neovascular membranes (1-5).
      Light-induced clotting of blood within these abnormal vessels could provide a
      novel method for the ablation of deleterious neovascularization. Thrombin is a
      serine proteinase that participates in the final stages of the coagulation
      cascade. An inhibitor of thrombin, p-Amidinophenyl-(E)-4-diethylamino-2-hydroxy
      alpha-methylcinnamate hydrochloride, MeCINN (1), covalently attaches to the
      active site serine hydroxyl, inhibiting or caging, the enzyme. Photolysis of the
      caged-thrombin in vitro causes a trans-cis isomerization of MeCINN which leads to
      regeneration of active enzyme and cleaving of fibrinogen into fibrin (6). Using a
      rabbit model of corneal neovascularization, we found that light at 366 nm safely
      and effectively photoactivates intravenous caged-thrombin and produces localized
      thrombosis in vivo. These results suggest that intravascular photoactivation of
      caged-thrombin could be used to occlude abnormal blood vessels in the human eye.

PMID- 9268173
TI  - The role of a decision rule in symptomatic pulmonary embolism patients with a non
      high probability ventilation-perfusion scan.
AB  - BACKGROUND: In order to improve the use of information contained in the medical
      history and physical examination in patients with suspected pulmonary embolism
      and a non-high probability ventilation-perfusion scan, we assessed whether a
      simple, quantitative decision rule could be derived for the diagnosis or
      exclusion of pulmonary embolism. METHODS: In 140 consecutive symptomatic patients
      with a non-high probability ventilation-perfusion scan and an interpretable
      pulmonary angiogram, various clinical and lung scan items were collected
      prospectively and analyzed by multivariate stepwise logistic regression analysis
      to identify the most informative combination of items. RESULTS: The prevalence of
      proven pulmonary embolism in the patient population was 27.1%. A decision rule
      containing the presence of wheezing, previous deep venous thrombosis, recently
      developed or worsened cough, body temperature above 37 degrees C and multiple
      defects on the perfusion scan was constructed. For the rule the area under the
      Receiver Operating Characteristic curve was larger than that of the prior
      probability of pulmonary embolism as assessed by the physician at presentation
      (0.76 versus 0.59; p = 0.0097). At the cut-off point with the maximal positive
      predictive value 2% of the patients scored positive, at the cut-off point with
      the maximal negative predictive value pulmonary embolism could be excluded in 16%
      of the patients. CONCLUSIONS: We derived a simple decision rule containing 5
      easily interpretable variables for the patient population specified. The optimal
      use of the rule appears to be in the exclusion of pulmonary embolism. Prospective
      validation of this rule is indicated to confirm its clinical utility.

PMID- 9268174
TI  - D-dimer determination to assess regression of deep venous thrombosis.
AB  - A number of studies evaluating deep venous thrombosis (DVT) have demonstrated
      that plasma levels of thrombotic and fibrinolytic parameters change during
      treatment, but the relationship between thrombus regression and evolution of
      these markers remains unknown. The objective of the present study was to
      correlate levels of D-Dimer (DD) with thrombus regression as assessed by duplex
      scanning. From 44 patients treated for acute DVT, DD were determined at diagnosis
      and at the end of initial heparin therapy of at least 5 days. Thrombus regression
      was measured by repeated duplex scanning at diagnosis and after 1 and 3 months.
      DD significantly decreased during heparin treatment as compared with values at
      presentation. DD levels were significantly higher in the group of patients
      without normalization of the DVT after 3 months (p = 0.003). A ninefold excess
      tendency was seen for DD levels > 1200 ng/ml at the end of initial treatment to
      be associated with poor resolution of the DVT [odds ratio 9.0, 0.95 confidence
      interval (CI) 2.3-35.4]. When the patients with an established malignancy were
      excluded, the differences were even more significant (p = 0.0004 for DD levels
      after initial treatment and an odds ratio of 17.5, 0.95 CI 3.3-92.5). These
      results suggest that increased DD levels after the initial phase of treatment are
      related to poor resolution of DVT after 3 months. These findings contribute to
      further insight into the process of thrombus regression. Furthermore high DD
      levels might help to identify the patients with a poor prognosis and could be
      useful to judge the efficacy of anticoagulant treatment.

PMID- 9268175
TI  - A 6-month venographic follow-up in 164 patients with acute deep vein thrombosis.
AB  - A total of 164 patients were recruited from a randomized trial comparing a low
      molecular weight heparin, dalteparin, given subcutaneously once daily with a
      continuous intravenous infusion of unfractionated heparin in the initial
      treatment of acute deep vein thrombosis. The primary objective of this follow-up
      study was to investigate whether there were any differences between the two
      treatment groups with respect to Marder score changes 6 months after the initial
      diagnosis using repeated venography. The secondary objectives were to analyse
      whether certain haemostatic and acute phase parameters or patient characteristics
      influenced the venographic outcome. RESULTS: Complete lysis of the thrombus was
      observed in 38.4% of the patients and a partial lysis in another 54.3% assessed
      by venography 6 months after the acute event. Extension of the thrombus was seen
      in 7.3% of the patients. There were no significant differences in the change in
      mean Marder score before treatment and at the 6 month follow-up between the two
      treatment groups, irrespective of thrombus localisation. In a regression model,
      male gender, low levels of orosomucoid and increased levels of d-dimer in plasma
      on day 5 were independently associated (p <0.05) with an enhanced absolute
      resolution of the thrombus at 6 months. No differences in symptoms and signs in
      the thrombotic leg at follow-up, comparing the treatment given, or thrombus
      extension at diagnosis and 6 months later, were demonstrated. CONCLUSION:
      Dalteparin given once daily subcutaneously was as effective as continuous
      intravenous infusion of unfractionated heparin in the initial treatment of deep
      vein thrombosis assessed by Marder score evaluation 6 months after the acute
      event.

PMID- 9268176
TI  - Chronic alcoholism decreases polyunsaturated fatty acid levels in human plasma,
      erythrocytes, and platelets--influence of chronic liver disease.
AB  - The effect of chronic ethanol ingestion on fatty acid composition of plasma,
      erythrocyte and platelet phospholipids and on plasma 6-keto-PGF1alpha was
      studied. Two groups of alcoholic subjects, one of them with chronic liver
      disease, were studied and compared to a control group of healthy subjects.
      Linoleic acid was not affected by alcoholism but its larger metabolites
      arachidonic acid (20:4n6) and docosatetraenoic acid (22:4n6) tended to be lower
      in erythrocytes and platelets of both groups of alcoholic patients; the decrease
      was more marked in the presence of chronic liver disease. Docosahexaenoic acid
      (22:6n3) was markedly decreased in plasma, erythrocytes and platelets obtained
      from alcoholic patients with chronic liver disease. Plasma levels of 6-keto
      PGF1alpha, a metabolite of prostacyclin (PGI2), remained unchanged. We conclude
      that chronic ethanol ingestion induces important changes in long-chain
      polyunsaturated fatty acids, mainly in platelets, and that these changes are
      exacerbated when patients suffer from chronic liver disease.

PMID- 9268177
TI  - Transfusion requirements are correlated with the degree of proteolysis of von
      Willebrand factor during orthotopic liver transplantation.
AB  - During orthotopic liver transplantation (OLT) excessive bleeding is the main
      cause of death and graft failure. The acute bleeding tendency that accompanies
      OLT, particularly during the anhepatic period and after reperfusion of the graft,
      is due to the depletion or functional abnormalities of several hemostasis
      components caused by the enhanced activity of enzymes such as plasmin, trypsin
      and leukocyte proteases. We surmised that enhanced proteolysis might also cause
      abnormalities of von Willebrand factor (vWF), and that these abnormalities are
      implicated in the bleeding tendency that develops during OLT. Therefore, the
      pattern of vWF proteolysis was studied with 16 patients with chronic liver
      disease, in serial blood samples obtained before OLT, during the anhepatic stage,
      after graft reperfusion and at the end of the surgical procedure. vWF became
      markedly degraded during the anhepatic and reperfusion stages, as shown by the
      partial loss of high molecular weight multimers, the relative decrease of the
      intact 225 kD subunit and the increase of the native proteolytic fragments of 176
      and 140 kD. Novel proteolytic fragments also became detectable. Using monoclonal
      antibody epitope mapping, it could be demonstrated that some of the proteolytic
      fragments corresponded in apparent molecular mass to those produced in vitro by
      incubating purified vWF with plasmin or elastase, but other fragments could not
      be attributed to these proteases. During the anhepatic and reperfusion stages
      there was a significant correlation between the degree of vWF degradation and the
      total amount of blood components transfused to replace blood losses. To evaluate
      whether or not vWF degradation could be controlled by the administration of a
      broad-spectrum protease inhibitor such as aprotinin, 5 patients were given a
      bolus dose of 500,000 U before surgery followed by 100,000 U/h during surgery, 5
      were given a 2,000,000 U bolus followed by 500,000 U/h, and no aprotinin was
      given to the remaining 6 patients. There were no differences in the patterns or
      degrees of vWF degradation between patients treated with aprotinin or not. In
      conclusion, there is a marked degradation of a key hemostasis protein during OLT.
      These alterations may be of clinical significance, because they are correlated
      with the transfusion requirements.

PMID- 9268178
TI  - A comparison of thromboelastography with heparinase or protamine sulfate added in
      vitro during heparinized cardiopulmonary bypass.
AB  - Thromboelastography (TEG) has been used after cardiopulmonary bypass (CPB) to
      diagnose excessive postoperative hemorrhage. Conventional TEG during CPB is not
      possible due to the sensitivity of the TEG to even small amounts of heparin,
      which produces a nondiagnostic tracing. The purpose of this study was to compare
      heparin neutralization using heparinase or protamine in TEG blood samples
      obtained during CPB. TEG testing was performed on 48 patients before, during and
      after CPB. Tissue plasminogen activator activity and antigen were measured on a
      subset of 32 patients. We found: 1) heparinase neutralized at least 10 IU/ml
      heparin while 1.6 ug/ml protamine neutralized up to 7 IU/ml heparin, 2) in
      samples with complete heparin neutralization by both methods, there was no
      significant difference in the R values, 3) while there was good correlation for
      other TEG parameters between heparinase and protamine treated samples, heparinase
      treatment produced shorter K values and higher angle, MA and A60, 4) while
      fibrinolysis was detected using both methods, heparinase treatment suppressed
      fibrinolysis in the TEG in both samples from patients and after in vitro addition
      of tissue plasminogen activator, 5) TEG was not a sensitive indicator of t-PA
      activity, detecting only 21% of samples with increased t-PA activity during
      bypass, and 5) heparinase was at least 100 times more expensive than protamine.
      We conclude that while both heparinase and protamine can be used to neutralize
      heparin in TEG samples obtained during CPB, protamine neutralization is more
      sensitive to fibrinolysis and less expensive, but the protamine dose must be
      carefully selected to match the heparin level used at individual institutions.

PMID- 9268179
TI  - Homocysteine metabolism in endothelial cells of a patient homozygous for
      cystathionine beta-synthase (CS) deficiency.
AB  - Homocystinuria due to cystathionine beta-synthase (CS) deficiency is the most
      common inborn error of methionine metabolism. Patients with CS-deficiency have an
      extremely high risk of vascular disease. The underlying mechanism is still
      unsolved. Dysfunction of endothelial cells could be the trigger in the formation
      of atherosclerosis and thrombosis. Therefore, differences in cell function were
      studied between normal and CS-deficient human umbilical endothelial cells
      (HUVECs). Total homocysteine (tHcy) concentrations in culture media as a measure
      of homocysteine export increased in all cell lines, including the cell line with
      CS-deficiency, with constant amounts of approximately 2.5 microM every 24 h. von
      Willebrand factor (vWF), tissue plasminogen activator (tPA) and plasminogen
      activator inhibitor (PAI-1) in culture media were used as markers of endothelial
      function and increased also with progression of culture time. The effects of
      additions of folate, vitamin B6 and methionine to the culture medium were
      studied. The homocysteine export and the markers of endothelial function did not
      differ between the control and the CS-deficient HUVECs under various test
      conditions. These data show that CS-deficient endothelial cells have normal
      homocysteine export and normal endothelial cell function. In CS-deficient
      patients the very high blood levels of homocysteine, probably due to deficient CS
      function in liver and kidney, seems to be the hazardous factor to endothelial
      cells, thus promoting atherosclerosis and thrombosis in CS-deficient patients.

PMID- 9268180
TI  - Factor XI activation by meizothrombin: stimulation by phospholipid vesicles
      containing both phosphatidylserine and phosphatidylethanolamine.
AB  - The activation of factor XI by meizothrombin was investigated using recombinant
      meizothrombin (R155A meizothrombin) that is resistant to autocatalytic removal of
      fragment 1. Meizothrombin was capable of activating factor XI at an activation
      rate similar to that of thrombin. Dextran sulphate and heparin, known cofactors
      of thrombin-mediated factor XI activation, did not stimulate the activation of
      factor XI by meizothrombin. However, the activation of factor XI by meizothrombin
      was markedly enhanced by vesicles containing phosphatidylcholine (PC),
      phosphatidylserine (PS) and phosphatidylethanolamine (PE), whereas PC/PS or PC/PE
      vesicles only had a minor effect on the activation. Thrombin-mediated factor XI
      activation was not influenced by phospholipids. The effect of PC/PS/PE and PC/PS
      vesicles was studied in a factor XI dependent clot lysis assay. In this assay,
      factor XI inhibits clot lysis by a feedback loop in the intrinsic pathway via
      thrombin-mediated factor XI activation. Removal of endogenous phospholipids in
      plasma by centrifugation resulted in an increased clot lysis, which could be
      restored to the pre-centrifugation level by the addition of PC/PS/PE vesicles,
      but not by PC/PS vesicles. When clot lysis was initiated by factor IXa in the
      presence of a factor XIa blocking antibody, there was no difference in inhibitory
      effect of PC/PS/PE or PC/PS vesicles. These data suggested that the differences
      in clot lysis inhibition observed between PC/PS/PE and PC/PS vesicles were caused
      by factor XI activation by meizothrombin. Meizothrombin-mediated factor XI
      activation may therefore play an important role in the antifibrinolytic feedback
      loop in the intrinsic pathway.

PMID- 9268181
TI  - Physical activity, fibrinogen plasma level and gene polymorphisms in
      postmenopausal women.
AB  - The relations between habitual physical activity (PA), fibrinogen gene
      polymorphisms and plasma fibrinogen were investigated in 191 postmenopausal
      women. Subjects who reported PA at least 4 times/week had lower fibrinogen level
      (3.19 g/l; 95% CI 3.10; 3.27) than women reporting PA 2-3 times/week (3.43 g/l;
      3.29; 3.58) or sedentary subjects (3.64 g/l; 3.33; 3.94). There were no
      differences in plasma fibrinogen across the alpha-fibrinogen (RsaI, TaqI) or beta
      fibrinogen (MnlI, BclI, HindIII) genotypes, the frequencies of which were in a
      Hardy-Weinberg equilibrium. An interaction between RsaI, which was in complete
      linkage disequilibrium with TaqI, and PA on plasma fibrinogen was observed, even
      after adjustments for BMI, smoking and medication (p = 0.024). Among women
      homozygous for the common RsaI allele, the physically most active had lower
      fibrinogen level (p <0.001) compared to the physically less active subjects.
      These results suggest that, in postmenopausal women, the relation between
      physical activity and plasma fibrinogen is modulated by genetic variation in the
      alpha-fibrinogen gene.

PMID- 9268182
TI  - Effect of strenuous exercise on fibrinogen and fibrinolysis in healthy elderly
      men and women.
AB  - The elevated incidence of thrombotic disease in elderly people may be associated
      with an increase in PAI-1 and fibrinogen with ageing. Cross-sectional studies
      report an inverse relation of PAI-1 and fibrinogen with physical activity, but
      training studies show inconsistent results. In a controlled intervention study
      among elderly subjects (aged 60-80 years) we observed a moderate decrease in PAI
      1 antigen (4%, -2.1 +/- 2.4 ng/ml), a significant increase in t-PA activity (11%,
      0.07 +/- 0.04 IU/ml) and an unexpected significant increase in fibrinogen (6%,
      0.18 +/- 0.07 g/l) in subjects following a 6-month intensive training program as
      compared to controls. Reduction in PAI-1 antigen was significantly associated
      with a decrease in triglycerides (beta = 10.3 ng/ml per 1 mM, p <0.01) and
      insulin (beta = 2.37 ng/ml per 1 mU/l, p = 0.07). Increase in fibrinogen
      coincided with a rise in C-reactive protein (p <0.001). These data suggest that
      regular intensive activity may increase fibrinolytic activity in a moderate way,
      but also may cause chronically elevated plasma levels of acute phase proteins in
      elderly persons.

PMID- 9268183
TI  - Heat stability of two candidate international reference preparations for
      recombinant human tissue factor.
AB  - Adequate heat stability of international reference preparations (IRP) for
      thromboplastin (tissue factor) is an essential requirement. Accelerated
      degradation testing was performed by three laboratories on two candidate IRP for
      recombinant human tissue factor. Heat treatment of these candidates resulted in
      slight shortening of the PT, contrasting with heat-induced prolongation of the PT
      observed with a conventional human brain derived IRP. Heat stability of these
      candidates was improved when compared with the stability of previous recombinant
      human tissue factor preparations. The PT-ratio did not change significantly when
      the candidates were stored for 28 days at 44 degrees C. It can therefore be
      concluded that both candidates are acceptable with regard to stability.

PMID- 9268184
TI  - Determination of the International Sensitivity Index of a new near-patient
      testing device to monitor oral anticoagulant therapy--overview of the assessment
      of conformity to the calibration model.
AB  - A key issue for the reliable use of new devices for the laboratory control of
      oral anticoagulant therapy with the INR is their conformity to the calibration
      model. In the past, their adequacy has mostly been assessed empirically without
      reference to the calibration model and the use of International Reference
      Preparations (IRP) for thromboplastin. In this study we reviewed the requirements
      to be fulfilled and applied them to the calibration of a new near-patient testing
      device (TAS, Cardiovascular Diagnostics) which uses thromboplastin-containing
      test cards for determination of the INR. On each of 10 working days citrated
      whole blood and plasma samples were obtained from 2 healthy subjects and 6
      patients on oral anticoagulants. PT testing on whole blood and plasma was done
      with the TAS and parallel testing for plasma by the manual technique with the IRP
      CRM 149S. Conformity to the calibration model was judged satisfactory if the
      following requirements were met: (i) there was a linear relationship between
      paired log-PTs (TAS vs CRM 149S); (ii) the regression line drawn through patients
      data points, passed through those of normals; (iii) the precision of the
      calibration expressed as the CV of the slope was <3%. A good linear relationship
      was observed for calibration plots for plasma and whole blood (r = 0.98).
      Regression lines drawn through patients data points, passed through those of
      normals. The CVs of the slope were in both cases 2.2% and the ISIs were 0.965 and
      1.000 for whole blood and plasma. In conclusion, our study shows that near
      patient testing devices can be considered reliable tools to measure INR in
      patients on oral anticoagulants and provides guidelines for their evaluation.

PMID- 9268185
TI  - The VITA project: phenotypic resistance to activated protein C and FV Leiden
      mutation in the general population. Vicenza Thrombophilia and Atherosclerosis.
AB  - Resistance to activated protein C (APC) has been recently identified as a common
      abnormality of the clotting system that significantly increases the risk of
      venous thromboembolism. The distribution of plasma response to APC in the general
      population and the variables potentially influencing it are however unknown. In
      this study, we analyzed the data from the first 4,000 subjects enrolled in the
      Vicenza Thrombophilia and Atherosclerosis (VITA) Project to identify the
      demographic and laboratory variables affecting the plasma response to APC. Plasma
      response to APC, expressed as APC-ratio, was significantly influenced not only by
      the presence of the FV Leiden mutation but also by the aPTT ratio, triglycerides,
      fibrinogen and cholesterol level and by pill use, ABO blood group, gender, smoke,
      body-mass index and age. The effect of these variables was independent of the
      presence of the FV Leiden mutation, and adjustment for their effect improved the
      discriminating efficiency of the APC-ratio for the presence of the FV Leiden
      mutation. Notwithstanding adjustment, the APC ratio was unsuitable for screening
      purposes in the general population (positive predictive value 82.7%).

PMID- 9268186
TI  - Effect of depolymerized holothurian glycosaminoglycan (DHG) on tissue factor
      pathway inhibitor: in vitro and in vivo studies.
AB  - Depolymerized holothurian glycosaminoglycan (DHG) is a glycosaminoglycan
      extracted from the sea cucumber Stichopus japonicus Selenka. In previous studies,
      we demonstrated that DHG has antithrombotic and anticoagulant activities that are
      distinguishable from those of heparin and dermatan sulfate. In the present study,
      we examined the effect of DHG on the tissue factor pathway inhibitor (TFPI),
      which inhibits the initial reaction of the tissue factor (TF)-mediated
      coagulation pathway. We first examined the effect of DHG on factor Xa inhibition
      by TFPI and the inhibition of TF-factor VIIa by TFPI-factor Xa in in vitro
      experiments using human purified proteins. DHG increased the rate of factor Xa
      inhibition by TFPI, which was abolished either with a synthetic C-terminal
      peptide or with a synthetic K3 domain peptide of TFPI. In contrast, DHG reduced
      the rate of TF-factor VIIa inhibition by TFPI-factor Xa. Therefore, the effect of
      DHG on in vitro activity of TFPI appears to be contradictory. We then examined
      the effect of DHG on TFPI in cynomolgus monkeys and compared it with that of
      unfractionated heparin. DHG induced an increase in the circulating level of free
      form TFPI in plasma about 20-fold when administered i.v. at 1 mg/kg. The
      prothrombin time (PT) in monkey plasma after DHG administration was longer than
      that estimated from the plasma concentrations of DHG. Therefore, free-form TFPI
      released by DHG seems to play an additive role in the anticoagulant mechanisms of
      DHG through the extrinsic pathway in vivo. From the results shown in the present
      work and in previous studies, we conclude that DHG shows anticoagulant activity
      at various stages of coagulation reactions, i.e., by inhibiting the initial
      reaction of the extrinsic pathway, by inhibiting the intrinsic Xase, and by
      inhibiting thrombin.

PMID- 9268187
TI  - Absolute and comparative subcutaneous bioavailability of ardeparin sodium, a low
      molecular weight heparin.
AB  - Ardeparin sodium (Normiflo, Wyeth-Ayerst) is a low molecular weight heparin
      undergoing clinical evaluation as an antithrombotic agent. The objective of this
      study was to evaluate the absolute and comparative bioavailability of ardeparin
      following subcutaneous administration of three different formulations [two
      formulations of ardeparin at 10,000 anti-factor Xa (aXa) U/ml, but with different
      preservatives, and a 20,000 aXa U/ml formulation]. The study was conducted using
      a randomized 4-period crossover design (three subcutaneous treatments and one
      intravenous treatment) in 24 healthy subjects, and the pharmacokinetics of
      ardeparin were characterized by plasma anti-factor IIa (aIIa) and anti-factor Xa
      (aXa) activities. The mean absolute bioavailability of ardeparin based on aIIa
      activity ranged from 62% to 64% and the mean absolute bioavailability based on
      aXa activity ranged from 88% to 97%. Based on bioequivalence testing criteria,
      the three ardeparin formulations were bioequivalent.

PMID- 9268188
TI  - Comparison of the effects of different low molecular weight heparins on the
      hemostatic system activation in vivo in man.
AB  - In a double-blind, randomized, cross-over study the effects of single
      subcutaneous doses of 120 anti-Xa units/kg body wt. of three different low
      molecular weight heparin (LMWH) preparations were investigated in 15 healthy
      subjects by determination of thrombin-antithrombin III complex (TAT), prothrombin
      fragment 1.2 (f1.2), and beta-thromboglobin (beta-TG) in shed blood and in venous
      blood. Certoparin, dalteparin, and enoxaparin significantly inhibited coagulation
      activation marker formation in shed blood. The substantial inhibition of TAT and
      f1.2 formation was slightly more pronounced in response to certoparin. beta-TG
      was decreased following certoparin and enoxaparin, but not following dalteparin.
      However, no difference between groups was detectable. A small but consistent
      decrease of f1.2 formation in venous blood was noted for all LMWHs and dalteparin
      and enoxaparin, but not certoparin, inhibited TAT formation. Only a minor impact
      of the three LMWH preparations was noted on beta-TG plasma concentrations. Our
      data indicate that the studied LMWH preparations have a major impact on blood
      clotting in the activated state and inhibit in vivo the hemostatic system to a
      comparable extent.

PMID- 9268189
TI  - The migration of human smooth muscle cells in vitro is mediated by plasminogen
      activation and can be inhibited by alpha2-macroglobulin receptor associated
      protein.
AB  - The plasminogen activation system is thought to be important in cell migration
      processes. A role for this system during smooth muscle cell migration after
      vascular injury has been suggested from several animal studies. However, not much
      is known about its involvement in human vascular remodelling. We studied the
      involvement of the plasminogen activation system in human smooth muscle cell
      migration in more detail using an in vitro wound assay and a matrix invasion
      assay. Inhibition of plasmin activity or inhibition of urokinase-type plasminogen
      activator (u-PA) activity resulted in approximately 40% reduction of migration
      after 24 h in the wound assay and an even stronger reduction (70-80%) in the
      matrix invasion assay. Migration of smooth muscle cells in the presence of
      inhibitory antibodies against tissue-type plasminogen activator (t-PA) was not
      significantly reduced after 24 h, but after 48 h a 30% reduction of migration was
      observed, whereas in the matrix invasion assay a 50% reduction in invasion was
      observed already after 24 h. Prevention of the interaction of u-PA with cell
      surface receptors by addition of soluble u-PA receptor or alpha2-macroglobulin
      receptor associated protein (RAP) to the culture medium, resulted in a similar
      inhibition of migration and invasion. From these results it can be concluded that
      both u-PA and t-PA mediated plasminogen activation can contribute to in vitro
      human smooth muscle cell migration and invasion. Furthermore, the interaction
      between u-PA and its cell surface receptor appears also to be involved in this
      migration and invasion process. The inhibitory effects on migration and invasion
      by the addition of RAP suggests an involvement of a RAP sensitive receptor of the
      LDL receptor family, possibly the LDL-receptor related protein (LRP) and/or the
      VLDL receptor.

PMID- 9268190
TI  - Sympathoadrenal activation and muscarinic receptor stimulation induce acute
      release of tissue-type plasminogen activator but not von Willebrand factor across
      the human forearm.
AB  - We have previously shown that both mental stress and administration of the
      muscarinic receptor agonist methacholine induce an acute release of tissue-type
      plasminogen activator (t-PA) across the human forearm. There are data indicating
      that the regulated acute release of t-PA from the endothelium is closely
      interrelated with release of von Willebrand factor (vWF). The aim of the present
      study was to simultaneously determine basal and stimulated in vivo release rates
      of t-PA and vWF in an intact human muscle vascular bed. Eighteen healthy young
      males were studied at rest and during 10 min of mental stress (forced
      arithmetic). A subsample of ten subjects also received a step-wise i.a. infusion
      of methacholine (0.1-0.8-4.0 microg/min). Forearm blood flow was determined by
      venous occlusion plethysmography and interconverted to forearm plasma flow (FPF)
      using individual hematocrits. Net release/uptake rates of t-PA and vWF were
      calculated as the product of the arteriovenous concentration gradient and FPF. At
      rest there was a net release of both t-PA antigen and activity. In contrast,
      there was no significant local net release of vWF antigen across the forearm. Net
      release rates of t-PA roughly doubled in response to the stress test (0.4 to 0.8
      and 0.2 to 0.5 ng x min(-1) x 100 ml(-1) for t-PA antigen and activity,
      respectively, p <0.05 for both). Local administration of methacholine induced a
      more than 10-fold increase in the net release rates of t-PA (0.6 to 9.6 and 0.3
      to 6.6 ng x min(-1) x 100 ml(-1) at the highest dose step for antigen and
      activity respectively, p <0.01 for both). In contrast, neither mental stress nor
      local administration of methacholine induced a significant net release of vWF
      antigen across the forearm. The results demonstrate that the processes of acute
      release of t-PA and vWF are not necessarily linked in vivo in man.

PMID- 9268191
TI  - Identification of PDGF receptors on human megakaryocytes and megakaryocytic cell
      lines.
AB  - Platelet-derived growth factor (PDGF) is a potent chemotactic and mitogenic
      factor implicated to play important roles in a variety of normal and
      pathophysiologic settings. We investigated PDGF receptor expression on human
      megakaryocytes and several megakaryocytic cell lines (CHRF, DAMI, Meg-01, M-07e)
      using enzyme-linked immunosorbent assay (ELISA), flow cytometry and
      immunocytochemical staining. Both PDGF receptor subtypes were identified on CHRF,
      DAMI, and Meg-01 cells by ELISA; PDGF beta-receptor levels exceeded alpha
      receptor levels. Flow cytometry revealed that beta-receptor levels on CHRF and
      DAMI cells exceeded those on Meg-01 cells, and that M-07e expressed neither
      receptor. Immunocytochemical staining confirmed these findings and determined
      that bone marrow megakaryocytes also expressed PDGF receptors. Exposure of
      megakaryocytes to PDGF-BB dramatically induced the expression of the immediate
      early gene, c-fos, within 30 min. Moreover, PDGF-BB significantly stimulated CHRF
      proliferation and colony formation. The present study demonstrates the presence
      of functional PDGF receptors on human megakaryocytes and their ability to mediate
      a mitogenic response.

PMID- 9268192
TI  - Thrombospondin induces dimerization of membrane-bound, but not soluble CD36.
AB  - CD36 is a cell surface receptor that has been shown to interact with a large
      variety of ligands including thrombospondin, collagen, Plasmodium falciparum
      infected erythrocytes, apoptotic neutrophils, modified low density lipoproteins,
      anionic phospholipids and long chain fatty acids. A number of these CD36 ligands
      elicit the transduction of intracellular signals involved in cell activation and
      internalization of bound ligands. The engagement of CD36 possibly activates three
      cytosolic protein tyrosine kinases that are presumably associated with the C
      terminal cytoplasmic tail of CD36. However, the mechanisms by which CD36
      functions in ligand binding and signal transduction are poorly understood. In the
      present study, a membrane-bound and a truncated soluble form of CD36 were
      expressed in HeLa cells and analyzed by velocity-gradient centrifugation and
      chemical cross-linking. We show that membrane CD36 exists predominantly as a
      monomer but a homodimeric form is also found. In contrast, soluble CD36
      sedimented in sucrose gradient as a monomer. However, when incubated with
      thrombospondin, the membrane form of CD36 predominantly sedimented as a dimer
      whereas soluble CD36 was monomeric. This study shows that thrombospondin has the
      ability to induce dimerization of CD36 and may be implicated in the signal
      transduction capacity of this adhesion molecule.

PMID- 9268193
TI  - Effect of a new monoclonal anti-glycoprotein IX antibody, KMP-9, on high shear
      induced platelet aggregation.
AB  - Human platelet glycoprotein Ib/IX complex acts as a receptor for von Willebrand
      factor. It is widely accepted that glycoprotein Ib is the essential receptor
      component, but the role of glycoprotein IX is still unclear. We produced a new
      monoclonal anti-glycoprotein IX antibody (KMP-9) by the hybridoma technique using
      platelets from a patient with Glanzmann's thrombasthenia. The epitope of KMP-9
      was localized to the C-terminal 8 kD fragment of glycoprotein IX using ELISA
      analysis of polyethylene-pin-synthesized peptides, as well as Western blot
      analysis of platelets after digestion with N-glycosidase and Staphylococcus
      aureus V8 protease. KMP-9 partially inhibited high shear stress-induced platelet
      aggregation, but had no effect on aggregation induced by ristocetin or low shear
      stress. Its inhibitory effect on high shear stress-induced aggregation was weaker
      than that of anti-glycoprotein Ib or anti-glycoprotein IIb/IIIa monoclonal
      antibodies. A 21-mer synthetic peptide (glycoprotein IX L110-G130) inhibited the
      binding of KMP-9 to platelets. It also competively inhibited the suppression of
      high shear stress-induced platelet aggregation by KMP-9, but had no direct effect
      on this aggregation. KMP-9 may be useful to clarify the physiological role of
      GPIX.

PMID- 9268194
TI  - Activation of human platelets causes post-translational modifications to
      cytoplasmic dynein.
AB  - In our studies of human platelets we have detected the presence of the molecular
      motors kinesin and dynein. Dynein is present at a concentration (0.8 microg/g
      tissue) that is approximately 1/3 the concentration reported for neuronal tissue.
      Immunofluorescence microscopy of resting platelets shows that, while platelet
      microtubules are arranged in coiled hoops forming the marginal band in the
      cortical region of the platelet, dynein is distributed in a pattern of punctate
      staining throughout the cytoplasm of the platelets. Fractionation of unactivated
      platelets shows that dynein partitions to the soluble fraction. Stimulation of
      platelets with thrombin, ADP or epinephrine causes a partial translocation of
      dynein from the soluble fraction to the particulate fraction with thrombin being
      the most efficient agent at promoting this shift. Dynein intermediate chain
      recovered in the soluble fraction of disrupted platelets following activation
      displays a transient, time-dependent phosphorylation. In contrast, dynein
      intermediate chain recovered in the particulate fraction shows decreased
      phosphorylation. These results indicate that human platelets contain a complex
      microtubule-based system of motor proteins that is an integral part of the
      physiological changes occurring during platelet activation.

PMID- 9268195
TI  - Different requirement of intracellular calcium and protein kinase C for
      arachidonic acid release and serotonin secretion in cathepsin G-activated
      platelets.
AB  - Previous studies have shown that platelet stimulation with cathepsin G rapidly
      results in cytoplasmic calcium ([Ca2+]i) increase and activation of protein
      kinase C (PKC). To elucidate the relationship between these two biochemical
      events and their relative contribution to the regulation of platelet response to
      cathepsin G, arachidonic acid (AA) release and serotonin (5HT) secretion were
      studied. Platelets made Ca2+-depleted and -permeable by treatment with A23187
      were compared to intact platelets to better dissociate calcium changes from other
      receptor-stimulated events. AA release elicited by cathepsin G in intact
      platelets was prevented by the Ca2+ chelator BAPTA; in Ca2+-depleted, -permeable
      platelets AA was released in direct response to added Ca2+ and was not increased
      by simultaneous stimulation with cathepsin G. In intact platelets, PKC inhibition
      by Ro 31-8220 or PKC induction with PMA either enhanced or reduced, respectively,
      cathepsin G-induced AA release. Both BAPTA and Ro 31-8220 prevented 5HT secretion
      from intact platelets; however, in Ca2+-depleted, -permeable platelets, cathepsin
      G was able to evoke 5HT secretion and p47 phosphorylation independently of
      [Ca2+]i increase, both effects being hampered by Ro 31-8220. Ca2+ and PKC
      therefore regulate PLA2 activity and 5HT secretion in cathepsin G-stimulated
      platelets in a different manner: the former is mainly triggered by [Ca2+]i
      increase, while PKC represents the major factor in determining dense granule
      secretion.

PMID- 9268196
TI  - Platelet counts and aggregation measures in the incidence of ischaemic heart
      disease (IHD).
AB  - Although studies in those who have already experienced clinical episodes of
      ischaemic heart disease (IHD) have suggested properties of platelets influencing
      recurrence, there is limited information on the value of platelet tests in
      predicting first episodes of IHD. One study has suggested that a raised platelet
      count and increased aggregability in response to adenosine diphosphate (ADP) may
      increase IHD incidence but the numbers of IHD events involved were small. The
      larger Northwick Park Heart Study (NPHS) included platelet count and both ADP and
      adrenaline-induced aggregation and this paper presents their associations with
      subsequent IHD. Platelet counts were performed in 1369 white NPHS men aged
      between 40 and 64 at recruitment, of whom 181 subsequently experienced a major
      episode of IHD over a follow-up period of 16.1 years. Platelet count was
      unrelated to the incidence of IHD. ADP-induced aggregation was performed in a
      random sample of 740 men in whom 66 IHD events occurred during the subsequent
      10.1 years, aggregability being measured both as ED50, the ADP dose at which
      aggregation occurred at half its maximum velocity, and also as EMR, the maximum
      rate of aggregation achieved. Neither measurement showed any association with IHD
      incidence, nor did similar measurements in 460 men in whom adrenaline-induced
      aggregation was also carried out. There are at least three possible explanations
      for the lack of any association between the measures of aggregability used and
      IHD. First, the large within-person variability of platelet aggregation tests may
      make the demonstration of any associations difficult, though the study had
      reasonable power to show effects with ADP. Secondly, the tests used may not be a
      valid index of the contribution of platelet function to thrombosis and IHD.
      However, the clear effect of several personal and demographic influences
      associated with IHD on the tests used brings this explanation into question.
      Thirdly, the role of platelets in thrombogenesis may be determined mainly by
      plasma influences such as fibrinogen, rather than by intrinsic properties of
      platelets themselves. Platelet counts within the physiological range and the
      aggregation tests used in this and in some other studies are of no value as
      indices of the risk of first episodes of IHD.

PMID- 9268197
TI  - Plasma derived von Willebrand factor preparations: collagen binding and
      ristocetin cofactor activities.
AB  - Five plasma preparations (11 lots) used in the treatment of von Willebrand's
      disease (vWD) were evaluated. The collagen binding function of von Willebrand
      factor (vWF) containing preparations was compared with the ristocetin cofactor
      activity and the vWF antigen. Some preparations have higher ratio of functional
      activity (ristocetin cofactor and collagen binding) relative to the antigen than
      is found in normal plasma. The ristocetin cofactor activity and the collagen
      binding activity are tightly correlated (r = .95). Ultracentrifugal (UCF)
      analysis was used to compare the size distribution of vWf antigen, ristocetin
      cofactor and collagen binding activity. The sedimentation of all of the vWF
      parameters in the plasma products was slower than in plasma. In plasma products
      the ristocetin cofactor activity sediments the most rapidly, the collagen binding
      activity is slower and the antigen the slowest. The collagen/antigen ratio
      decreases with decreasing vWF size. Assignment of potency to vWF containing
      preparations utilizing the collagen binding activity may be more precise and as
      accurate as with the traditional ristocetin cofactor assay.

PMID- 9268198
TI  - Perturbation of platelet adhesion to endothelial cells by plasminogen activation
      in vitro.
AB  - To investigate whether the endothelium-platelet interactions may be altered by
      plasminogen activation, cultured human umbilical vein endothelial cells (ECs)
      were treated with tissue-type plasminogen activator (t-PA) in the presence of
      plasminogen, and platelet adhesion to ECs was subsequently measured by using a
      tapered flow chamber. Our results demonstrated that platelets adhered more
      readily to t-PA treated EC monolayer than to the control monolayer at all shear
      stress levels tested. This phenomenon was treatment time-dependent and dose
      dependent, and it could be blocked by adding plasmin inhibitors, such as epsilon
      amino caproic acid and aprotinin. Adherent platelets on t-PA treated EC monolayer
      underwent more severe shape change than those on the control monolayer. While the
      extracellular matrix directly treated with t-PA attracted less platelets than the
      control matrix did, platelet adhesion to the matrix that was produced by t-PA
      treated ECs was unaltered. These data suggest that t-PA treatment on ECs
      compromised antiplatelet-adhesion capability on their apical surface without
      altering the reactivity of their extracellular matrix towards platelets.

PMID- 9268199
TI  - Endothelium-derived nitric oxide decreases polymorphonuclear leukocyte
      interaction with the deeply injured arterial wall under intermediate and high
      shear conditions.
AB  - Previous studies have shown that nitric oxide (NO) inhibits specific agonist
      induced polymorphonuclear leukocyte (neutrophil) and platelet aggregation in
      vitro. However, the inhibitory effects of NO on neutrophil interaction with the
      deeply injured arterial wall under conditions of flow is unknown. Therefore, we
      investigated the influence of NO derived from the endothelium on neutrophil and
      platelet interactions with the downstream arterial media under controlled flow
      conditions. Porcine aortic media, simulating deep arterial wall injury, was
      exposed to flowing porcine non-anticoagulated arterial blood for 5 min at
      intermediate (1006 s(-1)) and high (3397 s(-1)) shear conditions, and deposition
      of radiolabeled neutrophils and platelets was quantified. Neutrophil deposition
      on the exposed arterial media was reduced, by more than 30%, by pretreatment of
      the endothelium with the physiological precursor of NO, L-arginine, from 84.1 +/-
      13.7 to 57.4 +/- 7.2 x 10(3)/cm2 (p < 0.05) at 1006 s(-1), and from 99.3 +/- 9.8
      to 65.5 +/- 8.7 x 10(3)/cm2 (p < 0.05) at 3397 s(-1) of shear rate, relative to
      control. Pretreatment of the endothelium with the inactive stereoisomer D
      arginine had no effect on neutrophil deposition. These specific inhibitory
      effects of L-arginine were completely abolished by the inhibitor of NO synthesis,
      N(omega)-nitro-L-arginine methyl ester (L-NAME) at both shear rates. Endothelial
      pretreatment with D-arginine, or with L-arginine, in the absence or presence of L
      NAME, did not significantly influence platelet interaction with the thrombogenic
      arterial media at intermediate and high shear rates. These results indicate that
      NO derived from the endothelium can modulate and has a greater influence on
      neutrophil, than on platelet, interaction with the injured arterial wall exposing
      the media under conditions of flow typical to moderately and severely stenosed
      arteries.

PMID- 9268200
TI  - Application of thrombin based fibrin glue and non-thrombin based batroxobin glue
      on intact human blood vessels: evidence for transmural thrombin activity.
AB  - An alternative method of uniting small diameter vessels to obtain tissue union
      while limiting the thrombogenic effect of suture placement at a vessel
      anastomosis involves the use of a thrombin based fibrin glue as a surgical
      sealant. This investigation addresses whether the in vitro application of a
      thrombin based glue (TG), or batroxobin glue (BG), a non-thrombin based glue made
      with the snake venom enzyme batroxobin, alters intravascular platelet deposition
      (PD) or cleaves blood fibrinogen, as measured by fibrinopeptide A (FPA)
      production, when the respective glue is applied to the external surface of an
      intact human placental artery or an artery with an anastomosis. When TG was
      applied to the adventitial surface of an intact vessel or an anastomosis (n = 7)
      of control and experimental vessels, there was a significant increase in
      intraluminal platelet deposition, an effect not realized with BG (n = 12, intact
      vessel TG p = 0.01, BG p = 0.66, anastomosis TG p <0.01, BG p <0.01). Both TG and
      BG significantly increased FPA levels when human whole blood was perfused through
      both intact vessels or vessels containing an anastomosis when compared to control
      vessels (intact vessel TG and BG p <0.01, anastomosis TG and BG p <0.01).
      Labelled thrombin studies document the rapid passage of thrombin through an
      intact vessel wall or vessels with an anastomosis when TG was applied to the
      adventitial surface of the vessel. The data suggest that TG and BG are drug
      delivery systems for their respective enzymes that either pass through or
      transfer a message across not only a surgically created anastomosis, but also an
      intact vessel wall.

PMID- 9268202
TI  - Desmopressin: twenty years after.

PMID- 9268201
TI  - Observations on the development of mural thrombi in chronic experimental
      aneurysms in sheep.
AB  - Observations were made on mural thrombi in experimental venous pouch aneurysms in
      sheep. Thrombi associated with mural tears and dissection consisted predominantly
      of laminated fibrin masking the earlier platelet deposition and infiltrating the
      wall to some extent. Thrombus growth was associated with platelet masses of Zahn
      and secondary fibrin deposition. Intervening spaces contained a variable quantity
      of coagulated plasma, fibrin mesh, leucocytes, disintegrating red cells and
      platelets rather than red thrombus as often suggested. Periodic deposition of
      platelet masses with surface rippling, the whorling patterns of laminated fibrin
      and mechanical disruption of red cells indicated the importance of haemodynamics.
      Coarse macroscopic lamination of mural thrombi was attributed in part to
      recurrent dissections between the wall and the mural thrombus and of the thrombus
      itself. These accounted for growth of thrombus with expansion of the wall and
      interference with organization of the thrombus. The model has proved suitable for
      the study of thrombogenesis and thrombus behaviour in aneurysms.

PMID- 9268203
TI  - Rapid elimination of a high-titered F VIII inhibitor by high dose recombinant F
      VIII combined with high dose immunoglobulin infusion.

PMID- 9268204
TI  - Multiplex PCR-mediated site-directed mutagenesis for one-step determination of
      factor V Leiden and G20210A transition of the prothrombin gene.

PMID- 9268205
TI  - Incidence of Arg506 --> Gln mutation (factor V Leiden) in Pima Indians.

PMID- 9268207
TI  - High frequency of the C677T mutation in the methylenetetrahydrofolate reductase
      (MTHFR) gene in Northern Italy.

PMID- 9268206
TI  - The prevalence of factor V Leiden (Gln506) in Polynesians.

PMID- 9268208
TI  - The human platelet antigen HPA-1a/1b (PI(A1)/PI(A2)) polymorphism and cerebral
      ischaemia.

PMID- 9268209
TI  - Nitrite and nitrate plasma levels, as markers of nitric oxide synthesis, in
      antiphospholipid antibodies-related conditions and in thrombotic thrombocytopenic
      purpura.

PMID- 9268210
TI  - Relationship of lupus anticoagulant, anticardiolipin, anti-beta2-GPI and anti
      prothrombin autoantibodies with history of thrombosis in patients with the
      clinical suspicion of APA-syndrome.

PMID- 9268211
TI  - Successful treatment of lupus anticoagulant-hypoprothrombinemia syndrome using
      intravenous immunoglobulins.

PMID- 9268212
TI  - Plasma levels of soluble Fc gamma receptors II (sCD32) and III (sCD16) in
      patients with heparin-induced thrombocytopenia.

PMID- 9268213
TI  - Plasma tissue factor reflects endothelial cell injury rather than upregulation of
      tissue factor expression.

PMID- 9268214
TI  - Heme oxygenase activity and immunohistochemical localization in bovine pulmonary
      artery and vein.
AB  - Recent studies suggest that carbon monoxide (CO) derived from heme oxygenase (HO)
      catalyzed metabolism of heme plays a role in the regulation of cell function and
      communication. In blood vessels, CO may regulate vascular smooth-muscle tone
      through the activation of soluble guanylyl cyclase, in a manner similar to that
      of nitric oxide. The objective of this study was to determine the relation
      between HO enzymatic activity and localization of HO protein in bovine pulmonary
      blood vessels. HO enzymatic activity was determined by quantitating the rate of
      CO formation in the microsomal fraction of homogenates of bovine pulmonary artery
      (BPA) and vein (BPV). HO protein was localized by immunohistochemical analysis of
      paraformaldehyde-fixed tissue by using polyclonal antibodies to inducible HO (HO
      1) and noninducible HO (HO-2). HO enzymatic activity was measured in BPA and BPV,
      which correlated with the presence of HO protein. In BPA, HO enzymatic activity
      was found in the adventitia and medial layer; HO protein was localized in the
      nerves and vasa vasorum of the adventitia and was found throughout the smooth
      muscle cells in the medial layer. The data clearly demonstrate the presence of HO
      enzymatic activity for the formation of CO in blood vessels that contain HO
      protein.

PMID- 9268215
TI  - Low-dose but not high-dose captopril increases parasympathetic activity in
      patients with heart failure.
AB  - Parasympathetic nervous activity (PSNA) is an important determinant of the risk
      of sudden death and outcome in patients with cardiovascular disease, so the
      effects of drug therapy on PSNA may be of prognostic importance in patients with
      chronic heart failure (CHF). The angiotensin-converting enzyme (ACE) inhibitors
      are the only drugs that are reasonably accepted to improve prognosis in such
      patients. Accordingly we determined PSNA by heart-rate variability (HRV) analysis
      in nine patients (four women and five men, aged 73.6 +/- 6 yrs) with heart
      failure (NYHA Classes II-III) and in sinus rhythm. HRV was determined during 20
      40 min supine rest at baseline and then at 2-weekly intervals during incremental
      dosing of oral captopril, 12.5 mg b.i.d., 25 mg b.i.d., and 50 mg b.i.d. Poincare
      plot and conventional time- and frequency-domain measures were used to analyze
      the data. Low-dose captopril (12.5 mg b.i.d.) resulted in an increase in SD delta
      RR (16.0 +/- 6.6 to 22.0 +/- 9.1 ms; p < 0.05). We previously validated this as a
      measure of PSNA. Higher dose captopril (25 mg b.i.d.) also produced an increase
      in PSNA activity (16.0 +/- 6.6 to 18.7 +/- 7.8 ms), although this failed to reach
      statistical significance. However, the highest dose of captopril (50 mg b.i.d.)
      reduced PSNA activity to near-baseline values, as shown by measures of HRV in
      both the time and frequency domains. These data suggest that only a low dose of
      captopril augments PSNA in patients with heart failure. Dosing of ACE inhibitors
      may be important in optimizing their benefit in CHF.

PMID- 9268216
TI  - Alteration of cytochrome P-450 isozymes by captopril and idrapril in hepatic and
      renal microsomes of normotensive and spontaneously hypertensive rats.
AB  - To examine the effects of angiotensin-converting enzyme (ACE)inhibitors such as
      captopril and idrapril on the P-450 system, these compounds were administered 100
      mg/kg i.p. for 4 days to spontaneously hypertensive (SHRs) and normotensive
      Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats; thereafter, the principal
      hepatic and renal microsomal monooxygenase activities were determined. In all the
      rat strains used, both captopril and idrapril decreased only the P-450 2C11, (as
      determined by immunoblotting) and its linked activities such as 16alpha-, 2alpha-
      and 17-testosterone hydroxylases. These changes were accompanied by a significant
      decrease of blood testosterone levels both in normotensive and, more markedly, in
      hypertensive rats and by a reduction of systolic blood pressure, but only in
      SHRs. Only in SHRs as well, the renal immunodetectable P-450 4A content and the P
      450 4A-dependent activities, such as the (omega)-lauric acid hydroxylase,
      diminished after captopril or idrapril treatment. These data suggest that the
      decrease of increased blood pressure in hypertensive SHRs by the ACE inhibitors
      may be linked to the downregulation of the circulating testosterone level, the
      renal P-450 4A expression, and the related formation of the potent
      vasoconstrictor (omega)-hydroxy arachidonic acid.

PMID- 9268217
TI  - Moderate alcohol feeding attenuates postinjury vascular cell proliferation in
      rabbit angioplasty model.
AB  - Our studies in the cholesterol-fed rabbit model indicate that moderate alcohol
      consumption reduces the risk of restenosis by preventing low-density lipoprotein
      (LDL) oxidation. Eighteen hypercholesterolemic rabbits underwent arterial injury
      by Fogerty balloon endothelial denudation of iliac arteries. Two weeks later,
      balloon angioplasty of atherogenic or atherosclerotic arterial segments was
      performed. Nine rabbits (control) received water ad lib, whereas nine rabbits
      (moderate alcohol treated) received an average of 2.5 ml alcohol per 500 ml water
      daily, from the day of feeding hypercholesterolemic diet until they were killed,
      10 weeks later. There was a 26% increase in lumen size of the moderate alcohol
      treated group compared with the control group. The percentage neointima formation
      (NI) values of the moderate alcohol-treated and control groups were 77 +/- 2.1
      and 61 +/- 1.9, respectively (p < 0.001). The lumen/neointima (L/NI) ratio of the
      moderate alcohol-treated group was 0.71 +/- 0.07 compared with the control group,
      0.33 +/- 0.04 (p < 0.001). The number of foam cells in the moderate alcohol
      treated group was threefold less than the control group [i.e., 1.4 +/- 0.4 and
      3.9 +/- 0.8, respectively (p = 0.005)]. The arterial lesion malondialdehyde (MDA)
      values of the control and the moderate alcohol-treated groups were 13.6 +/- 2.8
      and 4.4 +/- 0.5 (p = 0.004), respectively. By radioimmunoassay, the moderate
      alcohol-treated group had less macrophage chemotactic protein-1 (MCP-1; 3,277
      cpm/microg protein) and platelet-derived growth factor (PDGF; 2,261 cpm/microg
      protein) compared with the controls (MCP-1, 4,529 cpm/microg protein; PDGF, 3,583
      cpm/microg protein). Thus we conclude that low concentrations of alcohol reduce
      neointimal formation, and the extent of lipid oxidation, the number of foam cells
      in the neointimal area and may decrease the expression of MCP-1 and PDGF by
      reducing LDL oxidation in an animal model of postangioplasty restenosis.

PMID- 9268218
TI  - Concanavalin A, ribose, and adenine resuscitate preserved rat hearts.
AB  - Preserved hearts may have cardiac dysfunction associated with inadequate
      myocardial high-energy phosphates. To resuscitate preserved hearts, hearts from
      male Wistar adult rats were preserved in 4.0 degrees C cold-modified Krebs
      Henseleit buffer (pH 7.40) for 8 h, subjected to 30 min of reperfusion at 36.5
      degrees C with the administration of concanavalin A (Con A; 40 mg/L), ribose (0.1
      mM), and adenine (0.1 mM). In comparison with the normal control, the preserved
      group had a decrease in cardiac output (CO; p < 0.001), myocardial adenosine
      triphosphate (ATP; p < 0.001), and creatine phosphate (CP; p < 0.001), associated
      with an increase in myocardial Ca2+ (p < 0.01) and release of myocardial adenine
      nucleosides (ANs; p < 0.001). In comparison with the preserved group, the group
      reperfused with ribose and adenine had no improvement of these parameters (p >
      0.05). The group reperfused with Con A had an increase in CO (p < 0.01) and
      myocardial CP (p < 0.01), associated with a decrease in myocardial Ca2+ (p <
      0.05) and ANs release (p < 0.01), and no change in myocardial ATP. However, the
      group reperfused with Con A, ribose, and adenine achieved a significant increase
      in CO (p < 0.005), ATP (p < 0.005), CP (p < 0.005), and a decrease in myocardial
      Ca2+ (p < 0.01) and ANs release (p < 0.01). Data suggest that the combination of
      Con A, ribose, and adenine may resuscitate cold-preserved rat hearts.

PMID- 9268219
TI  - Selective antagonism of the ET(A) receptor reduces neointimal hyperplasia after
      balloon-induced vascular injury in pigs.
AB  - Balloon angioplasty has become an important intervention in clinical cardiology;
      however, the technique is associated with a high incidence of restenosis,
      requiring repeated procedures. Endothelin-1 (ET-1), specifically through its
      action on ET(A) receptors, has been implicated in the cell proliferation and
      subsequent neointimal formation that leads to restenosis. Therefore we examined a
      potent antagonist of the ET(A) receptor, A127722.5, in a pig model of balloon
      angioplasty in iliac and carotid arteries. Ten pigs received A-127722.5 (7.5
      mg/kg b.i.d.) orally, starting 3 days before angioplasty and continuing for 4
      weeks; 10 additional pigs were treated with the same dosing regimen of the
      angiotensin-converting enzyme (ACE) inhibitor captopril (3.0 mg/kg b.i.d.), while
      a third group of 10 animals received placebo. At 2 and 4 weeks after the start of
      treatment, these doses of the ET(A) receptor antagonist and ACE inhibitor blocked
      the presser responses induced by big ET-1 and angiotensin I, respectively. In the
      iliac arteries, neointimal formation, neointimal/medial ratio, and maximal
      neointimal thickness were all significantly reduced, and the residual lumen area
      was significantly increased in pigs treated with the ET(A) receptor antagonist
      compared with placebo and captopril-treated groups. Medial collagen content,
      collagen deposition, and medial growth also were significantly reduced relative
      to the placebo group. Beneficial effects also were observed in the carotid
      arteries, although the results were less striking. Captopril was ineffective in
      protecting against the effects of balloon angioplasty in both vessels. Our
      results indicate that an orally active and potent antagonist of the ET(A)
      receptor inhibits cell proliferation and synthesis of extracellular matrix in
      pigs and may provide an important therapeutic approach to the prevention of
      restenosis.

PMID- 9268220
TI  - Comparative effects of loratadine and terfenadine on cardiac K+ channels.
AB  - Nonsedating H1-receptor antagonists appear to have wide and variable effects on
      the QT interval, mediated through modulation of cardiac K+ channels. By using the
      whole-cell patch-clamp technique, we examined the effects of terfenadine,
      loratadine, and descarboethoxyloratadine on a large family of K+ channels in
      ventricular myocytes and in Xenopus oocytes expressing the HERG delayed
      rectifier. The channels studied included the inward rectifier (I(Kl)) of rat and
      guinea pig, the transient outward K+ current (I(to)) of rat, the maintained K+
      current (I(ped)) of rat, and the delayed rectifier K+ channels (I(Ks) and I(Kr))
      of guinea pig myocytes. Loratadine and descarboethoxyloratadine, at therapeutic
      concentrations (30 to 100 nM), had no measurable effect on any one of the five
      types of K+ channels studied. At higher concentrations, 0.3 to 1.0 microM, only
      terfenadine had a significant suppressive effect on I(Kl) and delayed rectifier
      K+ channels, I(Kr) and I(Ks). At higher concentrations (1 to 2.5 microM), there
      were marked differences in the ability of the three drugs to suppress the five K+
      channels. Generally, terfenadine was the most and loratadine, the least effective
      blocker of all K+ channels examined. The most susceptible K+ channels were the
      delayed rectifier channels (I(Ks) and I(Kr)) in guinea pig and I(ped) in rat
      myocytes. Comparative effects of loratadine and terfenadine examined on the I(Kr)
      channel (HERG) expressed in Xenopus oocytes suggest much higher affinity of this
      channel to terfenadine, such that 1 microM terfenadine completely suppressed the
      current, whereas loratadine had little or no effect. The preferential suppressive
      effect of terfenadine on the expressed HERG channel was consistent with data
      obtained on I(Kr) in isolated guinea pig ventricular myocytes. The strong
      suppressive effect of terfenadine, noted particularly on the I(Kr) and to a
      lesser extent on I(to), I(Kl), and I(Ks), may be the cause of the reported
      incidence of QT prolongation and arrhythmogenesis. The absence of significant
      effect of loratadine and descarboethoxyloratadine, especially on I(Kr), I(to),
      I(ped), and I(Kl), even at 100 x highest plasma concentrations achieved, may
      explain the absence of significant reports of QT prolongation and
      arrhythmogenesis by the latter drugs.

PMID- 9268221
TI  - Inhibiting cholesterol absorption with CP-88,818 (beta-tigogenin cellobioside;
      tiqueside): studies in normal and hyperlipidemic subjects.
AB  - CP-88,818 (beta-tigogenin cellobioside; tiqueside) is a synthetic saponin
      developed to treat hypercholesterolemia by inhibiting the absorption of biliary
      and dietary cholesterol. Two studies are reported here: one in patients to assess
      safety and efficacy, and one in normal volunteers to explore the mechanism of
      action. The former included 15 hypercholesterolemic outpatients [low-density
      lipoprotein cholesterol (LDL-C) > or = 160 mg/dl] treated with 1, 2, and 3 g of
      tiqueside daily (b.i.d.) in a crossover design for three 2-week treatment
      periods, each separated by a 3-week placebo period. The mechanistic study was
      conducted with 24 healthy male subjects who were randomized in a parallel group
      design to either placebo (n = 6) or tiqueside (2 or 4 g/day; n = 9 each) once
      daily for 3 weeks. All subjects in this study were fed a low-fat, low-cholesterol
      diet [National Cholesterol Education Program (NCEP) Step 1]. Fecal steroid
      excretion rates and plasma lipid levels were determined at baseline and after 3
      weeks of treatment. Fractional cholesterol absorption was measured before and
      after treatment by the continuous feeding, dual-isotope method. Tiqueside
      produced a dose-dependent reduction in plasma LDL cholesterol levels in the
      hypercholesterolemic patients. In the mechanistic study, it decreased fractional
      cholesterol absorption rates and increased fecal neutral sterol excretion rates,
      changes associated with trends toward lower LDL cholesterol levels. Other
      lipoprotein levels were unaffected, as were fecal fat and bile acid excretion and
      fat-soluble vitamin absorption. Thus tiqueside dose-dependently inhibits
      cholesterol absorption in humans, resulting in a reduction in serum LDL
      cholesterol levels.

PMID- 9268222
TI  - Selectivity of BMS-180448 on myocardial versus brain blood flow in dogs and
      ferrets.
AB  - Openers of adenosine triphosphate (ATP)-sensitive potassium channels relax
      vascular smooth muscle and protect ischemic myocardium. Cromakalim and BMS-180448
      are examples of this class of compounds. They are equipotent in their
      cardioprotective activity, but cromakalim and related compounds are extremely
      hypotensive, an activity that limits their use. The effects of cumulative i.v.
      doses of BMS-180448 or cromakalim on hemodynamics and regional blood flow
      (radiolabeled microspheres) were evaluated in pentobarbital-anesthetized dogs and
      ferrets. Both compounds significantly reduced mean arterial blood pressure,
      cromakalim after 0.03-0.04 mg/kg in both species, and BMS-180448 only after 10
      mg/kg in dogs and 30 mg/kg in ferrets. Neither drug affected cardiac output. BMS
      180448, like cromakalim, increased blood flow in the heart, with augmented
      regional left ventricular blood flow occurring more in the subepicardium than in
      the subendocardium. The effect of BMS-180448 on myocardial blood flow, in both
      the dog and ferret, occurred at doses that were less hypotensive than those of
      cromakalim. The most striking difference between the actions of these agents was
      seen in the brain where cromakalim, but not BMS-180448, increased blood flow in
      all regions. The results of these studies further demonstrate the myocardium
      specific vasodilator activity of BMS-180448. Moreover, the cerebral vasodilator
      effect of K(ATP) openers, which has been thought responsible for the occurrence
      of headache in clinical trials, has been found lacking in BMS-180448; this
      difference may represent a clear advantage in the pharmacologic profile of the
      agent.

PMID- 9268223
TI  - Stereoselective metabolism of fenoldopam and its metabolites in human liver
      microsomes, cytosol, and slices.
AB  - Fenoldopam is a racemic mixture (R-FEN, S-FEN) that is a selective dopamine (DA
      1) receptor agonist with pronounced cardiovascular and renal effects in humans.
      Metabolism of fenoldopam in human liver microsomes, cytosol, and slices was
      stereoselective for glucuronidation, sulfation, and methylation. Microsomal and
      cytosolic fractions were supplemented with appropriate cofactors to obtain enzyme
      activity. There was no evidence of metabolism of fenoldopam by cytochrome P-450.
      R-FEN was metabolized to fenoldopam-8-sulfate (8-SO4), 7-methoxy fenoldopam (7
      MeO), 8-methoxy fenoldopam (8-MeO), and two glucuronidated products. The 7-MeO
      formed with incubation of R-FEN in human liver slices was further metabolized to
      an unknown sulfated product. S-FEN was metabolized to fenoldopam-7-sulfate (7
      SO4), a second unknown sulfated product, 7-MeO, 8-MeO, and two glucuronidated
      products. Metabolism of S-FEN and R-FEN in human liver slices to 7-MeO occurred
      at the same rate, whereas further metabolism of 7-MeO was stereospecific and
      slower for the S-isomer of 7-MeO. Fenoldopam has served as an excellent model
      compound for comparison of metabolism in human liver slices with metabolism in
      subcellular fractions. The parallel pathways of fenoldopam metabolism lessen the
      possible impact of drug-drug interactions.

PMID- 9268225
TI  - The contractile mechanism of sodium metavanadate in isolated rat aortae.
AB  - The mechanism of contractile effect of vanadate was investigated in rat aortae.
      Sodium metavanadate (NaVO3; 10(-5)-3 x 10(-3) M) induced contractile responses in
      a concentration-dependent manner. Removal of endothelium did not affect the
      response to NaVO3. The response to NaVO3 was inhibited by nifedipine, a voltage
      operated Ca2+ channel (VOC) inhibitor; NCDC, a phospholipase C inhibitor; and H
      7, a protein kinase C inhibitor, but not by prazosin, an alpha1-adrenoceptor
      antagonist; methysergide, a serotonin-receptor antagonist; tripelennamine, a
      histamine-receptor antagonist; glibenclamide, an adenosine triphosphate (ATP)
      dependent K+-channel inhibitor; or iberiotoxin, a large-conductance Ca2+
      activated K+-channel inhibitor. In addition, genistein or tyrphostin A48,
      tyrosine kinase inhibitors, did not affect the contraction induced by NaVO3. Mg2+
      removal or antimycin A, a Ca2+-ATPase inhibitor, did not cause any contraction.
      Ouabain, a Na+, K+-ATPase inhibitor, or K+-free medium caused the contraction of
      the aortae. The maximal contraction induced by NaVO3 plus ouabain was similar to
      that induced by NaVO3 alone. In addition, the response to NaVO3 was inhibited by
      AA861, a 5-lipoxygenase inhibitor, and RHC-80267, a diacylglycerol (DAG) lipase
      inhibitor. In the presence of AA861, either H-7 or nifedipine further inhibited
      the residual response to NaVO3. In the presence of NCDC, however, AA861 failed
      further to affect the residual response to NaVO3. In rat aortae, NaVO3 increased
      the levels of inositol monophosphate (IP) and prostaglandin F2alpha (PGF2alpha).
      AA861 and NCDC inhibited the IP increase. In addition, NCDC inhibited the
      PGF2alpha increase. These results suggest that the response to NaVO3 in rat
      aortae may be mainly the result of the increased phosphoinositide metabolism.

PMID- 9268224
TI  - Effect of AT1 angiotensin-receptor blockade on structure and function of small
      arteries in SHR.
AB  - The structure and function of small arteries of different vascular beds in
      spontaneously hypertensive rats (SHRs) are altered relative to Wistar-Kyoto (WKY)
      control rats, and these differences may be blunted under treatment with
      angiotensin-converting enzyme inhibitors. To determine whether this effect of
      angiotensin-converting enzyme inhibitors was caused by the interruption of the
      renin-angiotensin system, our experiments were conducted with an AT1 angiotensin
      receptor antagonist to evaluate its ability to induce regression of hypertrophy
      of resistance arteries in SHRs. The result of treatment of SHRs with losartan, an
      orally active selective angiotensin AT1 receptor antagonist was examined at a low
      (20 mg/kg/day) and a high (60 mg/kg/day) oral dose in SHRs once blood pressure
      had been elevated for some time. SHRs were treated for 12 weeks with losartan.
      Blood pressure was significantly reduced by losartan treatment from 210 +/- 2 mm
      Hg in untreated SHRs to 181 +/- 1 mm Hg (low dose) and 156 +/- 4 mm Hg (high
      dose) (p < 0.01). Cardiac and aortic hypertrophy were dose-dependently reduced in
      treated SHRs. Coronary, renal, mesenteric, and femoral small arteries (luminal
      diameter, 200-250 microm) studied on an isometric wire myograph and pressurized
      mesenteric small arteries examined under isobaric conditions exhibited
      significant hypertrophy and inward remodeling in SHRs in comparison to WKY rats.
      Losartan treatment resulted in a dose-dependent reduction in the media thickness
      and mediato-lumen ratio in small arteries from the four vascular beds studied on
      the wire myograph and in pressurized mesenteric small arteries. Endothelium
      dependent relaxation studied in pressurized arteries was enhanced, and
      acetylcholine-induced endothelium-dependent contractions studied on the wire
      myograph were abolished in losartan-treated SHRs relative to untreated SHRs. In
      WKY rats, treatment had no effect. These results demonstrate that treatment with
      the selective angiotensin II receptor antagonist losartan, even at doses that
      reduce blood pressure only moderately, induces regression of cardiovascular
      hypertrophy and of endothelial dysfunction in genetic hypertension in the rat.

PMID- 9268226
TI  - Interleukin-10 stimulation of endogenous nitric oxide release from human
      saphenous veins diminishes immunocyte adherence.
AB  - Interleukin-10 (IL-10) is described as a cytokine that exerts immune
      downregulating actions. In this regard, our study indicates that IL-10 activity
      on human saphenous veins is coupled to nitric oxide (NO) release. We demonstrated
      this phenomenon by using in vitro real-time amperometric measurement of NO levels
      in explanted human saphenous veins after IL-10 exposure. IL-10-induced NO release
      can inhibit the adherence of monocytes (75.7 +/- 15 cells/600 microm2 of
      endothelial surface) and granulocytes (65 +/- 18 cells/600 microm2 of endothelial
      surface) from control values (250-300 cells/600 microm2 of endothelial surface; p
      < 0.005). This inhibition is directly sensitive to NO synthase inhibition. The
      specificity of the IL-10 effects is shown by its sensitivity to antibody. In vivo
      measurement of IL-10 levels during and after cardiopulmonary bypass surgery
      indicated that they are higher at 6 h after skin closure (1,400 pg/ml) compared
      with levels found during surgery (300 pg/ml). We surmise that the postsurgical
      increase of IL-10 levels may be an immunoregulatory attempt to downregulate the
      diffuse inflammation that has been shown to be associated with cardiopulmonary
      bypass surgery.

PMID- 9268227
TI  - Inhibition of both aminopeptidase P and angiotensin-converting enzyme prevents
      bradykinin degradation in the rat coronary circulation.
AB  - Bradykinin (Bk), which is produced locally in the heart, exhibits potent
      cardioprotective effects. However, these effects appear to be limited by rapid
      degradation of the peptide. To determine the mechanism of Bk metabolism in the
      coronary circulation, [3H]Bk was perfused through the isolated rat heart via the
      aorta in the presence and absence of specific peptidase inhibitors. The
      radiolabeled metabolites were collected from the pulmonary artery and then
      separated, identified, and quantified by reversed-phase high-performance liquid
      chromatography (HPLC) by using a radioactive flow detector. In the absence of
      inhibitors, only 45 +/- 2% of the radioactivity eluted from the coronary
      circulation as intact [3H]Bk. The chromatograms suggested that Bk was being
      hydrolyzed at the Arg1-Pro2 bond by aminopeptidase P and at the Pro7-Phe8 bond by
      angiotensin-converting enzyme. When the aminopeptidase P inhibitor, apstatin (200
      microM), was coperfused with [3H]Bk, cleavage at the Arg1-Pro2 bond was blocked
      and the amount of intact [3H]Bk in the perfusate increased to 57 +/- 5% (p < 0.05
      vs. control). Coperfusion with the angiotensin-converting enzyme inhibitor,
      ramiprilat (0.5 microM), alone blocked cleavage at the Pro7-Phe8 bond and
      increased intact [3H]Bk to 75 +/- 3% (p < 0.001 vs. control). When both apstatin
      and ramiprilat were present, almost all of the radioactivity (96 +/- 1%) eluted
      as intact [3H]Bk (p < 0.01 vs. ramiprilat alone). The results indicate that the
      degradation of Bk in the rat coronary circulation can be fully accounted for by
      aminopeptidase P (approximately 30%) and angiotensin-converting enzyme
      (approximately 70%).

PMID- 9268228
TI  - Oxygen-induced pulmonary vasodilation is mediated by adenosine triphosphate in
      newborn lambs.
AB  - In the fetal lamb, oxygen-induced pulmonary vasodilation is attenuated by the
      combined use of purinergic receptor P1 and P2y antagonists, which block the
      effect of adenosine and adenosine triphosphate (ATP), respectively, and by
      N(omega)-nitro-L-arginine [an inhibitor of endothelium-derived nitric oxide
      (EDNO) synthesis]. In the newborn lamb, oxygen-induced pulmonary vasodilation is
      not blocked by N(omega)-nitro-L-arginine. We investigated the role of ATP and
      adenosine in oxygen-induced pulmonary vasodilation in eight newborn lambs with
      pulmonary hypertension induced by the thromboxane mimic, U46619. The hemodynamic
      effects of hyperoxia, ATP, adenosine, sodium nitroprusside (SNP), and
      acetylcholine (ACh) were compared before and after purinergic receptor blockade
      with Cibacron blue (CB, a P2y-receptor antagonist) and 8-phenyltheophylline (8PT,
      a P1-receptor antagonist) individually, together, and on a separate day, after
      infusion of N(omega)-nitro-L-arginine. During pulmonary hypertension, combined
      pretreatment with 8PT and CB attenuated the decrease in pulmonary arterial
      pressure caused by hyperoxia (11.3 vs. 35.2%), ATP (10.6 vs. 32.2%), and
      adenosine (1.9 vs. 33.7%) without change in the effect of ACh or SNP (p < 0.05).
      N(omega)-Nitro-L-arginine attenuated the pulmonary vasodilation caused by ATP and
      ACh but not by hyperoxia, adenosine, or SNP. In the newborn lamb, the pulmonary
      vasodilating effect of both oxygen and ATP are attenuated by combined P1 and P2y
      purinergic-receptor antagonists. Postnatally, oxygen-induced pulmonary
      vasodilation appears to be mediated by ATP through purinergic receptors.

PMID- 9268229
TI  - Cardiac heparin-releasable lipoprotein lipase activity in fructose-hypertensive
      rats: effect of coronary vasodilation.
AB  - Lipoprotein lipase (LPL) is an endothelium-bound enzyme that is rate determining
      for the clearance of triacylglycerol-rich lipoproteins. We assessed cardiac
      heparin-releasable LPL activity in an acquired model of hypertension, the
      fructose-hypertensive rat. Fructose feeding (10% solution in drinking water ad
      libitum) for 2 (short-term) or 4-6 (long-term) weeks induced hypertension,
      hypertriglyceridemia, and hyperinsulinemia in male Wistar rats. After short- and
      long-term fructose treatment, LPL activity in coronary perfusates was determined
      by retrogradely perfusing the hearts with heparin. Short-term fructose treatment
      did not alter cardiac heparin-releasable LPL activity, whereas a significant
      decrease in LPL activity was seen in the long-term treated group. Discontinuation
      of fructose treatment for 2 weeks from the long-term group normalized blood
      pressure and cardiac heparin-releasable LPL activity. Interestingly, acute
      vasodilation by in vitro perfusion of coronary vasodilators like nifedipine and
      CGS-21680 increased cardiac heparin-releasable LPL activity in the long-term
      group to control levels. These studies demonstrate that long-term fructose
      induced hypertension may play a significant role in regulating cardiac LPL
      activity. Whether or not this altered LPL activity has a role in the regulation
      of fatty acid supply to the hypertensive heart has yet to be determined.

PMID- 9268230
TI  - Effects of hypercholesterolemia on the contractions to angiotensin II in the
      isolated aorta and iliac artery of the rabbit: role of arachidonic acid
      metabolites.
AB  - The aim of this study was to investigate the effect of hypercholesterolemia on
      the angiotensin II-induced contractions in the isolated aorta and iliac artery of
      the rabbit, with respect to the role of arachidonate metabolites. Furthermore,
      the effect of the angiotensin-converting enzyme inhibitor ramipril was studied on
      the responses to angiotensin II in the cholesterol-fed rabbit. After 12 weeks of
      cholesterol diet (0.3%), endothelium-dependent relaxations to acetylcholine were
      significantly fewer compared with control (30.2 +/- 5.9% vs. 73.0 +/- 1.7%) in
      the aorta but not in the iliac artery of the rabbit. The angiotensin II- and
      methoxamine-induced contractions were also significantly lower compared with
      control in the aorta (101.4 +/- 6.7% vs. 60.9 +/- 4.2% and 160.2 +/- 5.7% vs.
      135.8 +/- 8.0%, respectively) but not in the iliac artery. The lipoxygenase
      inhibitor nordihydroguaiaretic acid (NDGA) selectively attenuated the angiotensin
      II-induced contractions in rabbit aortic rings from the control group only in the
      presence of the endothelium, whereas it had no effect on the responses to
      angiotensin II in the cholesterol group (with or without endothelium). In the
      iliac artery, NDGA inhibited the responses to angiotensin II in both the control
      and cholesterol groups. Treatment with ramipril (0.33 mg/kg/day) significantly
      improved the maximal angiotensin II-induced contraction in the aorta of rabbits
      fed a cholesterol diet for 16 weeks to 61.0 +/- 7.3% (vs. 32.7 +/- 9.0% in the
      cholesterol group). We conclude that hypercholesterolemia leads to a reduction of
      angiotensin II-induced contractions in the aorta and not in the iliac artery of
      the rabbit. This reduction might be related to loss of endothelium-dependent
      lipoxygenase products and is partially reversed by ramipril.

PMID- 9268231
TI  - Bioactivation of monocrotaline by P-450 3A in rat liver.
AB  - Monocrotaline (MCT) is bioactivated in liver cytochrome P-450s to MCT pyrrole
      (MCTP), which primarily injures the lung endothelium to result in the development
      of pulmonary hypertension (PH) in rats. However, whether there is a relation
      between the degree of PH and the activity of liver cytochrome P-450 to convert
      MCT to MCTP remains unclear. To examine the relation between these physiological
      and biochemical changes, we first measured the severity of MCT-induced (20 mg/kg)
      PH in male, female, castrated male, and phenobarbital (PB, liver P-450s inducer)
      pretreated male rats. The degree of right ventricular hypertrophy was more severe
      in PB-pretreated male than in control male rats. It was also more severe in male
      than in either female or castrated male rats, suggesting that sex-specific P-450s
      could be involved in the metabolic pathways of MCT in the liver. Further to
      explore which of the isozymes (2A2, 2C11, and 3A) of P-450s in the liver is
      responsible for the bioactivation of MCT, we measured the rate of MCTP production
      in hepatic microsomes by a modified Mattock's method. Treatment of male rats with
      PB and pregnenolone 16alpha-carbonitrile (PCN), which is the specific inducer of
      P-450 3A, increased the rate of MCTP production, suggesting that P-450 3A may
      contribute to the conversion to pyrrole. Therefore we measured the amount of P
      450 3A protein by immunoblotting and attempted to inhibit MCT metabolism by using
      antibodies to P-450 3A. P-450 3A was significantly induced by PCN (6.5-fold) and
      PB (4.6-fold) treatment and reduced by castration (0.38-fold). The amount of P
      450 3A was closely correlated with the production of MCTP, and the conversion of
      MCT to MCTP was strongly inhibited by antibodies against P-450 3A. These results
      indicated that P-450 3A was predominantly responsible for the metabolism of MCT
      to MCTP in rat liver and suggested a tight linkage between the degree of PH and
      the activity of liver P-450 3A.

PMID- 9268233
TI  - Comparison of the cardiovascular effects of the novel 5-HT(1B/1D) receptor
      agonist, SB 209509 (VML251), and sumatriptan in dogs.
AB  - The systemic cardiovascular effects of a novel 5-hydroxtryptamine (5-HT)(1B/1D)
      receptor agonist were investigated in the anaesthetised dog. SB 209509 (VML 251)
      was more potent than sumatriptan in producing increases in carotid vascular
      resistance after intravenous administration and was similar in potency to
      sumatriptan after sequential intraduodenal administration at 30-min intervals. In
      open-chest dogs, sequential intravenous administration of SB 209509 or
      sumatriptan produced marked increases in carotid vascular resistance without
      changing coronary vascular resistance. In contrast to sumatriptan, after
      administration of high doses of SB 209509 (>790 nmol/kg), a reduction in coronary
      vascular resistance was observed. After a single bolus intraduodenal dose of SB
      209509 (260, 520, or 790 nmol/kg), increases in carotid vascular resistance could
      be detected over a 5-h period. Sumatriptan (i.d.), 2.4 micromol/kg but not 700
      nmol/kg, produced a sustained effect similar to the effects of SB 209509 (790
      nmol/kg). In all experiments, SB 209509 and sumatriptan had minimal effects on
      arterial blood pressure or heart rate but produced marked changes in carotid
      vascular resistance over the same concentration range. SB 209509 was rapidly
      absorbed after intraduodenal administration in conscious dogs and had good
      bioavailability. These data indicate that SB 209509 is a potent 5-HT(1B/1D)
      receptor agonist that is rapidly absorbed from the duodenum. The effects of SB
      209509 are long lasting and selective for the carotid vascular bed.

PMID- 9268232
TI  - Effect of 17-beta estradiol in the rabbit: endothelium-dependent and -independent
      mechanisms of vascular relaxation.
AB  - Short-term estrogen administration has been independently proposed to produce
      arterial vasodilation by both an indirect mechanism and a direct mechanism
      (inhibition of calcium entry though the L-type calcium channel). The proposed
      contributions of such diverse mechanisms to the vascular actions of 17beta
      estradiol were examined in perfused hearts and in aortic ring sections isolated
      from female rabbits. In isolated rabbit hearts retrogradely perfused with
      Tyrode's solution, concentration-response curves to 17beta-estradiol (10(-9)-10(
      5) M) were performed under control conditions and during perfusion with Bay K8644
      (10(-7) M). 17beta-Estradiol produced a concentration-dependent decrease in
      coronary vascular resistance proportional to nitric oxide (NO) release in the
      presence and absence of Bay K8644. The addition of N(G)-nitro-L-arginine methyl
      ester (L-NAME; 10(-4) M) to the perfusate (a) completely inhibited NO formation,
      (b) produced a 2.3-fold and 1.55-fold rightward shift in the concentration
      response curve to 17beta-estradiol for Bay K8644 treated and control hearts,
      respectively, and (c) failed to prevent coronary artery vasodilation. In isolated
      aortic rings contracted with Bay K8644, 17beta-estradiol (10(-5) M) relaxed both
      intact (58%) and denuded (54%) aortic rings. L-NAME (10(-4) M) completely blocked
      NO release in intact rings but did not prevent relaxation in denuded aortic
      rings. The data demonstrate (a) an endothelium-dependent relaxation by 17beta
      estradiol, coincident with NO formation and suppressed by L-NAME, and (b) a
      direct relaxation of aortic and coronary smooth muscle independent of NO
      formation at higher 17beta-estradiol concentrations.

PMID- 9268234
TI  - Crossover trial of simvastatin versus pravastatin in patients with primary
      hypercholesterolemia.
AB  - The effects of simvastatin and pravastatin administered alone at initial doses of
      5 and 10 mg/day, respectively, on normalization of abnormal lipid metabolism in
      patients with hypercholesterolemia were evaluated by a crossover method. Patients
      whose serum levels of total cholesterol (TC) were > or = 220 mg/dl were randomly
      divided into two groups, and one of the groups (group S-P: 17 patients) was
      treated with simvastatin first and then with pravastatin whereas the other group
      (group P-S: 19 patients) was treated with pravastatin first and then with
      simvastatin. Simvastatin or pravastatin was replaced with the other drug after 8
      week administration in each group. These drugs were administered for 8 weeks
      each. Simvastatin and pravastatin significantly reduced the following serum
      lipids as compared with the levels in the observation period: TC by 23.2 +/- 8.1%
      and 18.1 +/- 10.9%, triglyceride (TG) by 13.0 +/- 24.7% and 5.8 +/- 47.1%, and
      low-density lipoprotein cholesterol (LDL-C) by 31.3 +/- 10.1% and 23.1 +/- 14.3%,
      respectively. TC and LDL-C levels were significantly (p < 0.001) lower and
      decreased to significantly (p < 0.001) greater degrees after simvastatin
      treatment than after pravastatin treatment. TC was normalized in 77.8% of the
      patients (28 of 36) after simvastatin treatment and in 68.9% of the patients (23
      of 36) after pravastatin treatment. LDL-C was normalized in 63.9% of the patients
      (23 of 36) after simvastatin treatment and in 44.4% of the patients (16 of 36)
      after pravastatin treatment. The percentage of patients whose LDL-C was
      normalized by simvastatin was significantly (p < 0.05) higher as compared with
      pravastatin. Results of this trial, which was conducted by a crossover method,
      show that the initial dose of simvastatin reduces serum cholesterol and LDL-C
      more potently than the initial dose of pravastatin in patients with
      hypercholesterolemia.

PMID- 9268235
TI  - Granule cell apoptosis and protein expression in hippocampal dentate gyrus after
      forebrain ischemia in the rat.
AB  - We investigated the relationship between apoptosis and selective protein
      expression in brain from rats subjected to 8 (n=10) or 12 min (n=10) of forebrain
      ischemia and 48 h of reperfusion, and control sham operated (n=2) and normal
      (n=2). Coronal sections were processed for double staining with DNA fragmentation
      detection and immunohistochemical staining. In five of ten 8-min ischemic and
      three of ten 12-min ischemic animals, nearly all dead granule cells within the
      dentate gyrus exhibited apoptotic morphology. In the remaining animals, no
      granule cell death was evident. In the pyramidal regions (CA1/2), nearly all dead
      cells were necrotic with only scattered apoptotic cells present. The
      immunoreactive expression of wt-p53, p53-response proteins (WAF1, Bax and
      Gadd45), and a cell cycle protein (cyclin D) were detected and preferentially
      localized to nuclei of apoptotic granule cells, and were weakly expressed in
      nuclei of necrotic pyramidal CA1/2 cells. Thus, 48 h after 8 or 12 min of
      forebrain ischemia in the rat, most pyramidal cells and dentate granule cells
      undergo distinct cell death pathways of necrosis or apoptosis, respectively. In
      addition, the selective expression of proteins associated with DNA damage and
      cell cycle in apoptotic dentate granule cells suggests a role for these proteins
      in the induction of apoptosis.

PMID- 9268236
TI  - Monoclonal remyelination-promoting natural autoantibody SCH 94.03:
      pharmacokinetics and in vivo targets within demyelinated spinal cord in a mouse
      model of multiple sclerosis.
AB  - Chronic inflammatory demyelination of the central nervous system is usually
      incompletely repaired. However, we previously reported that in vivo treatment
      with monoclonal antibody SCH 94.03 (produced using spinal cord homogenate as an
      immunogen) increased myelin repair 4-fold in the Theiler's virus mouse model of
      chronic progressive multiple sclerosis (Miller et al., 1994; J. Neurosci. 14:
      6230-6238). A major issue regarding site and mechanism of action of this antibody
      is whether SCH 94.03 enters demyelinated CNS lesions and reacts with
      oligodendrocytes and myelin. To address this question, we radiolabeled SCH 94.03
      and studied its distribution into tissues, pharmacokinetics, and binding to cells
      within demyelinating spinal cord lesions in vivo. SCH 94.03 distributed widely
      into extracellular water following intraperitoneal injection and was eliminated
      with a terminal half-life of 3-4.5 days. Only a portion of the total dose (0.4%)
      entered brain and spinal cord. SCH 94.03 accumulated 1.5-2.0-fold in brain
      between 1 and 7 days after injection, but its pharmacokinetics were otherwise
      similar to those of an isotype control IgMkappa antibody. Oligodendrocytes,
      myelin sheaths and, less frequently, axons were labeled within demyelinating
      lesions as detected by light and electron microscopic autoradiography. These
      findings suggest that remyelination-promoting autoantibodies could act within the
      demyelinating lesion of the central nervous system by binding to the
      oligodendrocyte, myelin, or axon.

PMID- 9268237
TI  - Cerebral oxygen transport and metabolism during graded isovolemic hemodilution in
      experimental global ischemia.
AB  - To verify the optimal hematocrit (Hct) level in the treatment of cerebral
      ischemia, cerebral oxygen transport (CTO2) and cerebral oxygen metabolism (CMRO2)
      in graded isovolemic hemodilution were evaluated during cerebral ischemia.
      Isovolemic hemodilution with low molecular weight dextran to stepwise lower Hct
      from 43% to 36%, 31%, and 26% was carried out in 13 splenectomized dogs, 6 h
      after global cerebral ischemia. Global ischemia of the animals was produced by
      multiple intra- and extracranial ligations of cerebral arteries. Cerebral blood
      flow (CBF) was measured with radioisotope labeled microspheres. CTO2, CMRO2, and
      oxygen extraction fraction (OEF) were calculated from CBF, arterial oxygen
      content (CaO2), and venous oxygen content (CvO2). In dogs with global cerebral
      ischemia, CBF increased with graded isovolemic hemodilution (r=-0.73, P<0.05).
      CTO2 reached its highest value at a Hct level of 31.3%. CTO2 at Hct of 36.1% and
      31.3% was statistically different from the value measured at a Hct of 43.3%, and
      there was a decrease when Hct was lowered to 25.9%. CMRO2 was the highest when
      Hct was at 31.3% and differed significantly from the value measured at a Hct of
      43.3%. There was a 10% increase of OEF when Hct was at 25.9%; however this change
      was not statistically significant compared with the OEF at Hct of 36.1% and
      31.3%, respectively. These findings indicate that CTO2 and CMRO2 were the highest
      when Hct was reduced to 31% in hemodilution. Hct at 31% is the optimum for
      cerebral metabolism in ischemic status. Uncoupling of CTO2, CMRO2 with CaO2 was
      also observed in this study. This phenomenon suggests that hemodilution to
      augment cerebral circulation may be at least partially attributed to the
      beneficial effects of hemorheologic improvement in the microcirculation of the
      ischemic brain.

PMID- 9268238
TI  - Decreased cerebrospinal fluid levels of neutral and basic amino acids in patients
      with Parkinson's disease.
AB  - We measured the CSF levels of 21, and the plasma levels of 26, amino acids in 31
      patients with Parkinson's disease (PD) and in 45 matched controls. We used an ion
      exchange chromatography method. When compared to controls, PD patients had lower
      CSF levels of taurine, alanine, valine, leucine, isoleucine, ethanolamine,
      citrulline, ornithine, lysine, histidine, arginine, and alpha-aminobutyric acid.
      PD patients not treated with levodopa or with dopamine agonists had higher CSF
      tyrosine and phenylalanine levels than those not treated with these drugs and
      also than controls. PD patients had higher plasma levels of phosphoserine,
      threonine, methionine, tyrosine, sarcosine and alpha-aminoadipic acid, and lower
      plasma levels of valine, leucine, and tryptophan, than controls. The CSF/plasma
      ratio of many of these amino acids was significantly lower in PD patients than
      those of controls, suggesting that PD patients might have a dysfunction in the
      transport of neutral and basic amino acids across the blood-brain barrier.

PMID- 9268239
TI  - Motor neuron disease following generalized fasciculations and cramps.
AB  - We report a case of motor neuron disease in which fasciculations and cramps
      progressed generally before the development of muscle wasting. After involvement
      of the upper and lower motor neurons became clinically manifest, widespread
      fasciculations and cramps persisted and accompanied pseudotetany. The present
      case suggests that spinal cord pathology of motor neuron disease can cause the
      abnormal excitability of the motor neurons, resulting in the development of
      generalized fasciculations and cramps.

PMID- 9268240
TI  - Analysis of the McLeod syndrome gene in three patients with neuroacanthocytosis.
AB  - McLeod syndrome is a rare X-linked disorder involving neurological defects and
      acanthocytosis. We examined the XK gene in three patients with
      neuroacanthocytosis, one of whom had cardiomyopathy, and his symptoms were very
      similar to those of McLeod syndrome. We found two new transversions (C to G at
      codon 204 and G to C at codon 205) in exon 3 in all those cases. However, the
      transversion at codon 205 was found in all 70 Japanese normal subjects and four
      non-Japanese (two Caucasian males, one Chinese female and one Micronesian female)
      and that at codon 204 was also detected in all 14 normal Japanese males and the
      four non-Japanese. These findings suggest that they are not the cause of McLeod
      syndrome, but normal polymorphisms which have not been reported. Moreover, there
      is a possibility that patients with neuroacanthocytosis similar to McLeod
      syndrome exist without the XK gene abnormalities.

PMID- 9268241
TI  - Anticardiolipin antibodies in ischemic stroke in the young: Indian experience.
AB  - Anticardiolipin antibodies (aCL) have been recognised as a marker for an
      increased risk of thrombosis. The prevalence of these antibodies in young Indian
      ischemic stroke population is not known. Our study establishes the prevalence of
      these antibodies and evaluates their clinical significance in 60 patients aged 40
      years or less who presented with completed ischemic stroke. Immunoglobulin G and
      immunoglobulin M class antibodies to anticardiolipin were determined using a
      standardized enzyme-linked immunosorbent assay. The prevalence of these
      antibodies in stroke patients was 23% compared to 3.2% in the controls. All
      patients studied had no overt evidence of systemic lupus erythematosus or related
      autoimmune disorders. The aCL-positive stroke patients did not differ
      significantly from aCL-negative stroke patients with regard to demographic
      characteristics, risk factor profile, and radiological features. Prior transient
      ischemic attacks, ischemic retinopathy, and asymptomatic infection were more
      frequent in the aCL-positive group. The role of anticardiolipin antibodies as a
      disease marker for ischemic stroke is under-recognised in India and warrants
      further investigation.

PMID- 9268242
TI  - Detection of three transthyretin gene mutations in familial amyloidotic
      polyneuropathy by analysis of DNA extracted from formalin-fixed and paraffin
      embedded tissues.
AB  - We identified three different missense mutations of the transthyretin (TTR) gene
      in three Japanese patients with familial amyloidotic polyneuropathy by analysis
      of their DNAs extracted from formalin-fixed and paraffin-embedded tissues.
      Patient 1 carried the TTR methionine-30 (Met) mutation (G to A transition at
      position 1679). DNA sequencing analysis of the TTR gene from patient 2 showed a G
      to T transversion at position 3830 in exon 3, resulting in an amino acid
      replacement of serine-50 (Ser) with isoleucine (Ile). Patient 3 had the novel
      mutation (G to T transversion at position 7314) in exon 4, resulting in an amino
      acid replacement of alanine-109 (Ala) with Ser. We established DNA diagnostic
      methods for detecting TTR Ile50 by polymerase chain reaction (PCR)-induced
      mutation restriction analysis and for TTR Ser109 by PCR-restriction fragment
      length polymorphism. Gene analysis of archival paraffin-embedded tissues is
      useful for the precise diagnosis of FAP and for clarifying its molecular
      pathogenesis in patients for whom fresh genomic DNA is not available.

PMID- 9268243
TI  - Long-term outcome following sympathectomy for complex regional pain syndrome type
      1 (RSD).
AB  - We performed a retrospective study of 29 patients with CRPS1 (RSD) who were
      initially examined between 1983 and 1993, and had either transthoracic (lower
      third of stellate ganglia to T3) or lumbar (L2-L4) sympathectomy. The patients
      were followed from 24 to 108 months after surgery. Patients with unsuccessful
      surgical outcomes had significantly longer duration of symptoms before surgery
      (median, 36 months) than those with successful outcomes (median, 16 months) by
      Wilcoxon rank sum test (chi2=8.69, df=1, P<0.01). All seven patients (100%) who
      had sympathectomy within 12 months of injury, nine of 13 patients (69.2%) who had
      sympathectomy within 24 months of injury, and only four of nine patients (44.4%)
      who had sympathectomy after 24 months of injury obtained permanent (greater than
      24 months) symptom relief. Patient age, sex, occupation, site of injury, type of
      injury, presence of trophic changes, and duration of follow-up were not
      significantly related (P>0.05) to surgical outcome.

PMID- 9268245
TI  - The reduction of androgen receptor mRNA in motoneurons of X-linked spinal and
      bulbar muscular atrophy.
AB  - We examined the expression level of androgen receptor (AR) messenger RNA (mRNA)
      in the motoneurons from patients with X-linked spinal and bulbar muscular atrophy
      (SBMA) and amyotrophic lateral sclerosis (ALS) using in situ hybridization.
      Although AR mRNA was detected in motoneurons from the SBMA patient, the
      expression level was lower than that from the patients with ALS, despite similar
      loss of motoneurons. The expression level of AR mRNA in the dorsal nucleus of
      Clarke from the patient with SBMA was similar to that in the patients with ALS,
      suggesting that the qualities of the mRNA were similar in each spinal cord sample
      and that AR mRNA was uniquely reduced in the motoneurons of the SBMA patient.
      Decreased levels of AR mRNA may be involved in the pathogenesis of SBMA resulting
      in degeneration of motoneurons.

PMID- 9268244
TI  - Skeletal muscle studies in patients with HIV-related wasting syndrome.
AB  - Previous reports have suggested that HIV-related wasting syndrome may be
      considered as a form of myopathy. The aim of the present study was to investigate
      histopathological muscle changes in HIV-related wasting syndrome in order to know
      if there is a common substrate and whether muscle plays a primary or secondary
      role in its development. Patients with wasting syndrome diagnosed by Centers for
      Disease Control (CDC) criteria were prospectively evaluated. Clinical,
      analytical, nutritional, anthropometrical and muscular data were recorded. The
      patients were subdivided into two groups: group A was constituted by patients in
      whom wasting syndrome was the AIDS-defining illness, and group B by patients in
      whom AIDS diagnosis was previously made. In all cases muscle biopsy was performed
      and processed for conventional stainings and histochemical reactions. Thirty
      patients were included (group A, 12; group B, 18). Clinical, analytical,
      nutritional and anthropometrical data did not essentially differ between the two
      groups. All patients were malnourished with respect to controls.
      Histopathological findings in muscle biopsy were heterogeneous and similar in
      both groups, except for HIV-related myopathies, which were more frequently seen
      in the patients from group A (P=0.05). In five cases (17%) an unsuspected and
      potentially treatable myopathy was diagnosed. Patients with polyarteritis nodosa
      (two) or polymyositis (one) were treated with prednisone, which improved their
      wasting syndrome. By contrast, patients with AZT-myopathy (two) did not improve
      when the drug was discontinued. We conclude that in most cases the wasting
      syndrome cannot be considered as a true myopathy, and probably metabolic and/or
      nutritional factors may account for wasting development. However, in a subset of
      patients muscle biopsy allows the diagnosis of a treatable myopathy leading to
      the improvement of wasting syndrome.

PMID- 9268247
TI  - Serum neuron-specific enolase levels do not increase after electroconvulsive
      therapy.
AB  - BACKGROUND: Cognitive disorders occurring after electroconvulsive therapy (ECT)
      are regarded as an expression of brain damage, despite computed tomography (CT)
      and magnetic resonance imaging (MRI) showing no signs of structural brain damage.
      Serum neuron-specific enolase (NSE) is a sensitive marker of neuronal damage
      (i.e., after stroke or cardiac arrest). The objective of this study was to
      investigate whether ECT leads to a rise in the serum NSE level as an expression
      of neuronal damage. METHODS: We investigated seven patients (four women, three
      men; mean age 6212 years) with major depressive disorder, who were treated with
      ECT for the first time. ECT was administered every 2 days, three times a week
      under standard conditions (anaesthesia: thiopental, succinylcholine, 100% oxygen,
      unilateral ECT, seizure duration more than 20 s). Blood samples were drawn at the
      following times. For the first ECT: 15 and 1 min before ECT, and 1, 5, 10, 15,
      20, 25, 30, 45, 60, 75, 90, 105, 120 min, and 8, 12, 24 h after ECT. For all
      subsequent ECT: 1 min before and 4 h after every ECT. Serum NSE was measured by
      means of enzyme immunoassay (Cobas Core NSE, EIA, Hoffmann-La Roche). RESULTS: On
      average, each patient underwent ECT 10 times (range 5-20). In the first ECT there
      was no difference in serum NSE levels before and at all times following ECT. A
      comparison of serum NSE levels before and after each subsequent bout of ECT
      revealed no differences. Moreover, comparing the baseline serum NSE levels
      (before the first ECT) with the values after final ECT showed no differences
      either. CONCLUSION: ECT did not increase serum NSE values, indicating that
      electroconvulsive therapy does not cause neuronal damage.

PMID- 9268246
TI  - Temporary amelioration of symptoms with intravenous cyclophosphamide in
      amyotrophic lateral sclerosis.
AB  - Based on the evidence that autoimmunity may play a role in the pathogenesis of
      amyotrophic lateral sclerosis (ALS), a variety of immunomodulating agents have
      been used in the treatment. In an uncontrolled trial we treated 44 patients of
      ALS with intravenous cyclophosphamide (IVCP) at a total dose of 1.5 g/m2 given
      over a period of 8 to 10 days. The patients were evaluated using neurological
      score which included bulbar, motor and daily activity scores before and following
      treatment. Twenty three patients showed a significant improvement (P=<0.001) in
      the composite and the individual scores. The improvement persisted only for 2 to
      3 months. Amongst them the severely (7) and moderately (16) affected (score less
      than or more than 150) showed almost a similar response to treatment. A
      comparison of the improved group of 23 patients with the unimproved group of 21
      patients did not reveal any significant factors which influenced the response to
      IVCP. However, there was a suggestion that patients below the age of 60 years and
      a duration of illness less than 12 months may respond to the drug. In conclusion,
      treatment with intravenous cyclophosphamide resulted in mild and temporary
      improvement in clinical status of the patients with amyotrophic lateral
      sclerosis. This may be considered as an alternative method of treatment in
      developing countries where newer drugs are not available and affordable.

PMID- 9268248
TI  - Reliability, validity, and composition of a subset of the Centers for Disease
      Control and Prevention acquired immunodeficiency syndrome knowledge questionnaire
      in a sample of homeless and impoverished adults.
AB  - OBJECTIVES: Measures of acquired immunodeficiency syndrome (AIDS)-related
      knowledge that have good psychometric properties are needed to evaluate the
      impact of educational interventions, particularly among impoverished populations.
      Few measures that satisfy these requirements are available. The authors describe
      the psychometric characteristics and composition of a subset of 21 AIDS knowledge
      items from the questionnaire used by the National Center for Health Statistics.
      METHODS: The study was conducted with a convenience sample of women and their
      significant others or close friends in nine homeless shelters and 11 residential
      drug recovery programs in the skid row area of Los Angeles from 1991 to 1993.
      Trained nurses and outreach workers collected data from 486 predominately African
      American adults before delivery of well-established, culturally sensitive AIDS
      educational intervention. A subset of 334 participants were re-interviewed 6
      months later. RESULTS: A total scale score was calculated from a one-factor
      solution, and two subscale scores were formed based on a two-factor solution. One
      subscale was composed of primarily cognitive items, whereas the second subscale
      contained mainly transmission-related items. The internal consistency reliability
      of the overall scale was 0.89; the two subscales had alphas of 0.80 and 0.92. The
      measures have face validity, and support for convergent validity was found.
      Further, even though AIDS knowledge in the sample was relatively high, all three
      measures showed marked improvement in the subsample of respondents who were re
      interviewed after receiving AIDS-related educational information. CONCLUSIONS:
      These measures show promise for assessing AIDS knowledge and the efficacy of AIDS
      education programs in vulnerable populations. The findings reported here,
      however, are preliminary. Test-retest reliability needs to be examined, and
      additional studies are needed with samples that are more culturally diverse and
      include socially isolated individuals.

PMID- 9268249
TI  - Discharge destination and repeat hospitalizations.
AB  - OBJECTIVES: Is discharge destination a determinant of readmission? Studies to
      date have been inconclusive. The primary purpose of this study was to identify
      the role of discharge destination in the occurrence of repeat hospitalizations
      for a national sample of patients discharged from Veterans Health Administration
      (VHA) hospitals. METHODS: The authors studied a 20% random sample of individual
      patients, 65 years of age or older, with either chronic obstructive pulmonary
      disease, stroke, or dementia who were discharged from a Veterans Health
      Administration hospital in 1988. All data for the study were obtained from
      secondary administrative sources. Multiple sources were used to determine
      discharge destination. The authors focused on personal home versus nursing home
      discharge destination. Both VHA and Medicare discharge data were used to track
      hospital readmissions. Proportional hazards regression models were used to
      examine the independent association of discharge destination with time to
      readmission within 30 days, 6 months, 1 year, and 2 years of discharge, adjusting
      for severity, other clinical and demographic characteristics, and censoring
      deaths. RESULTS: After adjustment and including out-of-system (Medicare) use, we
      found that patients with chronic obstructive pulmonary disease and patients with
      dementia who were discharged to nursing homes (community and Veterans Health
      Administration, respectively) were less likely to be readmitted within 30 days
      after discharge than patients discharged to personal homes. CONCLUSIONS: These
      findings have important implications for adjusting hospital performance profiles
      based on discharge destination and for focussing efforts to reduce the frequency
      and associated costs of hospital readmissions.

PMID- 9268250
TI  - Application of an analytic model to early readmission rates within the Department
      of Veterans Affairs.
AB  - OBJECTIVES: Adverse outcome rates are increasingly used as yardsticks for the
      quality of hospital care. However, the validity of many outcome studies has been
      undermined by the application of one outcome to all patients in large,
      diagnostically diverse populations, many of which lack evidence of a link between
      antecedent process of care and the rate of the outcome, the underlying assumption
      of the analysis. METHODS: To address this analytic problem, the authors developed
      a model that improves the ability to identify quality problems because it selects
      diseases for which there are processes of care known to affect the outcome of
      interest. Thus, for these diseases, the outcome is most likely to be causally
      related to the antecedent care. In this study of hospital readmissions, risk
      adjusted models were created for 17 disease categories with strong links between
      process and outcome. Using these models, we identified outlier hospitals.
      RESULTS: The authors hypothesized that if the model improved on identifying
      hospitals with quality of care problems, then outlier status would not be random.
      That is, hospitals found to have extreme rates in one year would be more likely
      to have extreme rates in subsequent years, and hospitals with extreme rates in
      one condition would be more likely to have extreme rates in related disease
      categories. It was hypothesized further that the correlation of outlier status
      across time and across diseases would be stronger in the 17 disease categories
      selected by the model than in 10 comparison disease categories with weak links
      between process and outcome. CONCLUSIONS: The findings support all these
      hypotheses. Although the present study shows that the model selects disease
      outcome pairs where hospital outlier status is not random, the causal factors
      leading to outlier status could include (1) systematic unmeasured patient
      variation, (2) practice pattern variation that, although stable with time, is not
      indicative of substandard care, or (3) true quality-of-care problems. Primary
      data collection must be done to determine which of these three factors is most
      causally related to hospital outlier status.

PMID- 9268251
TI  - Physical and cognitive functioning among chronically ill African-American and
      white elderly in home care following hospital discharge.
AB  - OBJECTIVES: Although race is recognized as an important variable in health status
      and medical care, the conditions of African-American and white elders have not
      been studied sufficiently as they enter home care after hospital discharge. This
      study tests hypotheses that African-American elders enter home care sicker, more
      dependent, and cognitively impaired. METHODS: Hypotheses were tested in two
      independent studies, both conducted in a Midwestern city. Study 1 compares the
      physical and cognitive conditions of 208 African-Americans and white elders
      discharged home after hospitalization for congestive heart failure. Data were
      obtained from medical records and from patient interviews. Study 2 compares the
      physical and cognitive conditions of 212 African-Americans and white elders
      discharged home after hospitalization for hip fracture, cerebral vascular
      accident, and congestive heart failure. Data were obtained from medical records
      and interviews with patients' discharge planners. RESULTS: African-Americans were
      found to go home more sick, more dependent, and more cognitively impaired,
      although no race difference was found in instability at discharge. CONCLUSIONS:
      These findings raise concerns about African-American elders' access to care in
      community settings, given their greater needs at discharge.

PMID- 9268252
TI  - Predicting psychiatric emergency admissions and hospital outcome.
AB  - OBJECTIVES: A decision support tool for psychiatric hospital admissions was
      developed and validated to provide reliable, clinically relevant information to
      providers and case managers. METHODS: Using the Severity of Psychiatric Illness
      rating system, an empirical model of psychiatric emergency decision-making was
      constructed and validated on a spilt sample of 254 crisis cases. RESULTS: Three
      dimensions of the Severity of Psychiatric Illness system-Suicide Potential,
      Danger to Others, and Severity of Symptoms-were used to construct a model that
      successfully predicted 73% of decisions about level of care (inpatient or
      outpatient). Clear misses, patients with a 0.20 probability of being hospitalized
      who were admitted, and patients with an 0.80 probability or greater of being
      hospitalized who were not admitted were reviewed to allow for utilization review.
      This decision support tool then was validated by predicting hospital outcomes in
      two additional samples. First, a random sample of consecutive admissions to a not
      for-profit psychiatric hospital were studied. Second, a panel of admissions from
      a large managed care firm were evaluated. CONCLUSIONS: Results demonstrate that
      the decision to hospitalize patients in psychiatric hospitals is rational and
      that models predicting admission also can predict in-hospital outcomes.

PMID- 9268253
TI  - The substitutability of adult foster care for nursing home care in Oregon.
AB  - OBJECTIVES: This study investigates the degree of substitutability of adult
      foster care for nursing home care in Oregon. METHODS: Using three tests, the
      authors determined (1) the extent to which an additional adult foster care
      resident in a county reduces the number of nursing home residents in that county,
      (2) which characteristics of residents and facilities are important in sorting
      residents into either nursing homes or adult foster care facilities, and (3) the
      price elasticity of demand for adult foster care, using the county as the unit of
      observation. RESULTS: It was found that for every additional foster care resident
      in a county, a nursing home loses 0.85 residents-almost a one-to-one substitution
      ratio. CONCLUSIONS: Despite the high degree of substitutability, residents
      perceive important differences in the characteristics of the two forms of care.
      Indeed, private residents are, on average, willing to pay twice as much for
      nursing home care as for adult foster care, suggesting that these differences are
      important. Finally, private consumers are sensitive to price differences among
      adult foster care facilities. The implications for policy are discussed.

PMID- 9268254
TI  - Determinants of regular source of care among homeless adults in Los Angeles.
AB  - OBJECTIVES: The authors explore the determinants of having a regular source of
      care in a community-based probability sample of homeless adults in Los Angeles.
      Results from this study should be more representative than those from previous
      studies of the homeless that are clinic- or shelter-based. In addition to those
      factors found to be barriers to regular sources of care in the general
      population, we hypothesized that psychosocial characteristics of the homeless and
      the homeless lifestyle would negatively impact their likelihood of having a
      regular source of care. METHODS: The authors conducted a multiple logistic
      regression to predict regular source of care among the homeless, using an
      adaptation of the Behavioral Model of health services utilization as an analytic
      framework. RESULTS: Fifty-seven percent of the sample reported that they had a
      regular source of care. Of those with a source of care, 30% reported a hospital
      outpatient department; 25% reported a community or homeless clinic; 23% reported
      a hospital emergency room; 14% reported a government clinic; and 9% reported a
      private physician's office as their source of care. Some factors found to be
      barriers to having a regular source of care in the general population (male,
      Hispanic, young age) also were barriers among homeless adults. Additional
      barriers in this sample included homelessness-related characteristics such as
      competing needs, long-term homelessness, and social isolation. Chronic mental
      illness and chronic substance dependence were not related to having a source of
      care among the homeless. Characteristics that increased the likelihood of having
      a regular source of care in the general population (poor health status, Medicaid)
      were not related to having a regular source of care among the homeless.
      CONCLUSIONS: In a context of limited resources, the distribution of regular
      source of care among the homeless appears to be highly inequitable. Although some
      of the characteristics identifying those with a regular source of care suggest
      differential patterns of behavior across subgroups, others suggest differential
      advantage in access to care and a lack of fit between the needs of the homeless
      and the organization of health services.

PMID- 9268256
TI  - An examination of cross-specialty linkage applied to the resource-based relative
      value scale.
AB  - OBJECTIVES: Analyses were performed to reproduce and examine the sensitivity of
      the cross-specialty linkage algorithm used by Hsiao et al(1) to obtain the
      currently implemented resource-based relative value scale for Medicare physician
      reimbursement. METHODS: The cross-specialty linkage procedure designed and
      implemented in Hsiao et al is an important component of the resource-based
      relative value scale underlying current Medicare Fee Schedule. This linkage
      procedure aligns independent intraspecialty relative value scales onto a common
      scale, and therefore determines the level of reimbursement accruing to each
      specialty. The complexity of the algorithm to perform this alignment has
      prevented critical review of the methodology. The authors examine the statistical
      properties of the algorithm, and diagnose its sensitivity from changes in the
      data and small modifications to the numerical procedure. RESULTS: Our examination
      of the linkage algorithm uncovered some issues requiring further consideration.
      These include the questions raised about the use of "biweighting," and about the
      benefits of incorporating correlation information into the analysis. Moreover,
      simulation analyses demonstrate that the existing relative value scale is
      sensitive to changes in the input data and methodology. Certain specialties'
      reimbursement can shift by as much as 32% using Hsiao's algorithm. Most
      importantly, the interspecialty linkage algorithm underlying the current fee
      schedule downweights pairs of linked services even when such links are deemed
      more important from a clinical point of view. As a result, in some cases
      clinically superior links received little or no importance in the algorithm.
      CONCLUSIONS: The cross-specialty linkage procedure described in Hsiao et al may
      not adequately perform the task of aligning intraspecialty relative value scales
      onto a common scale because of the sensitivity of the algorithm and the choice of
      statistical methodology. The authors suggest improvements to Hsiao's method
      resulting from our analyses. If widespread adoption of the Medicare Fee Schedule
      is a component of health care reform, reconsideration of the process determining
      each specialty's payment level assumes new importance.

PMID- 9268255
TI  - Achieving guidelines for the treatment of depression in primary care: is
      physician education enough?
AB  - OBJECTIVES: The authors examine whether physician education has enduring effects
      on treatment of depression. METHODS: Depressed primary care patients initiating
      antidepressant treatment from primary care clinics of a staff-model health
      maintenance organization were studied. Quasi-experimental and before-and-after
      comparisons of physician practices, supplemented with patient surveys, were used
      to compare the process of care and depression outcomes. Intervention consisted of
      extensive physician education that spanned a 12-month period. This included case
      by-case consultations, didactics, academic detailing (eg, clearly stating the
      educational and behavioral objectives to individual physicians), and role-play of
      optimal treatment. Main outcome measures were divided into two groups. Quasi
      experimental samples included: (1) antidepressant medication selection and (2)
      adequacy (dosage and duration) of pharmacotherapy. Survey samples included: (3)
      intensity of follow-up; (4) physician delivered educational messages regarding
      depression treatment; (5) patient satisfaction; and (6) depression outcomes.
      RESULTS: No lasting educational effect was observed consistently in any of the
      outcomes measured. CONCLUSIONS: There was no enduring improvement in the
      treatment of depression for primary care patients. Depression treatment
      guidelines were achieved contemporaneously, however, for intervention patients
      enrolled in a multifaceted program of collaborative care during the training
      period. These results suggest that continuing programs of reorganized service
      delivery to support the role of a primary care physician (eg, on-site mental
      health personnel, close monitoring of patient progress and adherence), in
      addition to physician training, are essential for the success of guideline
      implementation.

PMID- 9268257
TI  - Excluding nonusers: a source of bias in research on satisfaction with health
      services.

PMID- 9268258
TI  - AMA policy: covenants not to compete are unethical for physicians in training.
      Council on Ethical and Judicial Affairs, American Medical Association.

PMID- 9268259
TI  - Proponents gather to discuss practicing evidence-based medicine.

PMID- 9268260
TI  - Study examines stress-immune system links in women with breast cancer.

PMID- 9268261
TI  - From the Centers for Disease Control. Status of the Global Laboratory Network for
      poliomyelitis eradication, 1994-1996.

PMID- 9268262
TI  - From the Centers for Disease Control. Outbreak of cyclosporiasis--Northern
      Virginia-Washington, DC-Baltimore, Maryland, metropolitan area, 1997.

PMID- 9268263
TI  - From the Centers for Disease Control. Transmission of HIV possibly associated
      with exposure of mucous membrane to contaminated blood.

PMID- 9268264
TI  - From the Centers for Disease Control. Malaria in an immigrant and travelers-
      Georgia, Vermont, and Tennessee, 1996.

PMID- 9268265
TI  - A piece of my mind. Notes from the inner territories.

PMID- 9268266
TI  - Perioperative maintenance of normal temperature.

PMID- 9268267
TI  - Perioperative maintenance of normal temperature.

PMID- 9268268
TI  - Occupational exposure to silica and end-stage renal disease.

PMID- 9268269
TI  - Assessment of domestic violence at the scene of domestic assaults.

PMID- 9268270
TI  - Loading dose and monitoring of warfarin therapy.

PMID- 9268271
TI  - Differentiating dysplastic nevi from melanoma.

PMID- 9268272
TI  - Congenital adrenal hyperplasia and adult sexual behavior.

PMID- 9268273
TI  - Methemoglobinemia from artificial fingernail solution.

PMID- 9268274
TI  - Platelet transfusion reaction due to Yersinia enterocolitica.

PMID- 9268275
TI  - Risk of chronic arthropathy among women after rubella vaccination. Vaccine Safety
      Datalink Team.
AB  - CONTEXT: A review by the Institute of Medicine found a possible relationship
      between rubella vaccination and chronic arthritis among women. OBJECTIVE: To
      evaluate the risk of persistent joint and neurologic symptoms in rubella
      seronegative women subsequently vaccinated with RA 27/3 rubella vaccine. DESIGN:
      Retrospective cohort study based on computerized laboratory data and medical
      record review. Records were reviewed for symptoms occurring within 2 years before
      and after the date of serological testing and to identify vaccinees. Possible
      cases were evaluated by a rheumatologist blinded to serological findings and
      vaccination status. SETTING: Large health maintenance organization in northern
      California. PATIENTS: Women aged 15 to 59 years serotested for rubella during
      1990 with continuous health plan membership for 2 years before and after the date
      of their serological test. Seronegative women immunized within 1 year of
      serotesting (n=971) were defined as exposed. Primary comparison groups included
      all unvaccinated, seronegative women (n=924) and randomly selected seropositive,
      unvaccinated women (n=2421) matched to exposed subjects on serological test date
      and age (+/-3 years). MAIN OUTCOME MEASURES: Prevalence and incidence of chronic
      joint and neurologic symptoms during 1-year follow-up period stratified by age
      and serological findings, immunization, and postpartum status. RESULTS: No
      significantly increased risk was associated with receipt of rubella vaccine for
      any outcome except for prevalence of carpal tunnel syndrome in vaccinated women
      at least 30 years old compared with seropositive, unvaccinated women (2.9% vs
      1.4%; P=.03). A total of 34 women had onset of conditions within the 1-year
      follow-up period; 9 of these were in the group of seronegative, immunized women,
      of whom 6 had onset of symptoms within 6 weeks of vaccination. Among these 6
      women, symptoms included transient arthritis or arthralgias (<6 weeks duration)
      in 4 women, arthralgia of indeterminate chronicity in 1 woman, and carpal tunnel
      syndrome in 1 woman. Postpartum women across all groups were less likely to be
      seen for nontraumatic arthropathies than nonpostpartum women (4.5% vs 7.2%, P=.08
      in vaccinated women; 4.8% vs 8.1%, P=.09 in seronegative controls; and 4.8% vs
      10.0%, P=.01 in seropositive controls). CONCLUSIONS: In this large retrospective
      cohort analysis there was no evidence of any increased risk of new onset chronic
      arthropathies or neurologic conditions in women receiving the RA 27/3 rubella
      vaccine. These data support the continued vaccination of rubella-susceptible
      women to reduce the risk of congenital rubella syndrome.

PMID- 9268276
TI  - A randomized trial of a consultation service to reduce falls in nursing homes.
AB  - CONTEXT: Falls are a major health problem in nursing homes, but no interventions
      have been shown to prevent falls in nursing home residents. OBJECTIVE: To
      evaluate an intervention program designed to prevent falls and associated
      injuries in high-risk nursing home residents. DESIGN: Randomized controlled
      trial. SETTING AND PARTICIPANTS: Seven pairs of middle Tennessee nursing homes
      with 1 facility in each pair randomly assigned to the intervention. Facilities
      had 482 (261 control, 221 intervention) residents who qualified for the study
      because they had high risk of falls and a potential safety problem that could be
      addressed by the intervention. INTERVENTION: Comprehensive structured individual
      assessment with specific safety recommendations that targeted suboptimal
      practices for environmental and personal safety, wheelchair use, psychotropic
      drug use, and transferring and ambulation. Facility staff were encouraged to
      implement the individual recommendations and to improve overall facility safety.
      MAIN OUTCOME MEASURES: The mean proportion of recurrent fallers and incidence
      rate of injurious falls in the facility in the year following the intervention.
      RESULTS: The mean proportion of recurrent fallers in intervention facilities
      (43.8%) was 19.1% (95% confidence interval, 2.4%-35.8%) lower than that in
      control facilities (54.1%, P=.03). Intervention facilities had a nonsignificant
      trend toward a lower mean rate of injurious falls (13.7 vs 19.9 per 100 person
      years, reduction of 31.2%, P=.22). Subgroup analyses suggested greatest benefits
      for residents for whom the recommended interventions were carried out or who had
      3 or more falls in the preceding year. CONCLUSION: The high rate of falls and
      related injuries in nursing homes should not be viewed as inevitable, but as
      outcomes that can be substantially improved through structured safety programs.

PMID- 9268277
TI  - Outbreak of viral gastroenteritis due to a contaminated well. International
      consequences.
AB  - CONTEXT: Small round-structured viruses (SRSVs) are known to cause viral
      gastroenteritis, but until now have not been confirmed in the implicated vehicle
      in outbreaks. OBJECTIVE: Investigation of a gastroenteritis outbreak. DESIGN:
      After applying epidemiologic methods to locate the outbreak source, we conducted
      environmental and laboratory investigations to elucidate the cause. SETTING:
      Tourists traveling by bus through Alaska and the Yukon Territory of Canada.
      PARTICIPANTS: Staff of a restaurant at a business complex implicated as the
      outbreak source, convenience sample of persons on buses that had stopped there,
      and bus employees. MAIN OUTCOME MEASURES: Odds ratios (ORs) for illness
      associated with exposures. Water samples from the restaurant and stool specimens
      from tourists and restaurant staff were examined by nucleic acid amplification
      using reverse transcription polymerase chain reaction and sequencing of viral
      amplification products. RESULTS: The itineraries of groups of tourists
      manifesting vomiting or diarrhea were traced back to a restaurant where buses had
      stopped 33 to 36 hours previously. Water consumption was associated with illness
      (OR, 5.3; 95% confidence interval [CI], 2.3-12.6). Eighteen of 26 employees of
      the business complex were ill; although not the index case, an employee ill
      shortly before the outbreak lived in a building connected to a septic pit, which
      was found to contaminate the well supplying the restaurant's water. Genotype
      2/P2B SRSV was identified in stool specimens of 2 tourists and 1 restaurant
      employee. Stools and water samples yielded identical amplification product
      sequences. CONCLUSIONS: The investigation documented SRSVs in a vehicle
      epidemiologically linked to a gastroenteritis outbreak. The findings demonstrate
      the power of molecular detection and identification and underscore the importance
      of fundamental public health practices such as restaurant inspection, assurance
      of a safe water supply, and disease surveillance.

PMID- 9268278
TI  - Alcohol and illicit drug abuse and the risk of violent death in the home.
AB  - CONTEXT: While acute alcohol and illicit drug use are common in homicide and
      suicide victims, the role of chronic substance use in violent death is unclear.
      OBJECTIVE: To measure the magnitude of risk of violent death in the home
      associated with alcohol use or chronic abuse and use of illicit drugs. DATA
      SOURCES: Data obtained from a case-control study of risk factors for homicide and
      suicide in 3 large metropolitan areas of the United States. DESIGN: Matched case
      control study including 388 homicide cases, 438 suicide cases, and equal numbers
      of controls matched for age, sex, race, neighborhood, and county. Data were
      analyzed by means of conditional logistic regressions in which other potential
      risk factors for violent death were also considered. OUTCOME AND EXPOSURE
      MEASURES: Homicide and suicide victims were identified from medical examiner
      reports in Shelby County, Tennessee; King County, Washington; and Cuyahoga
      County, Ohio. Structured interviews were conducted with proxy respondents close
      to the decedents to obtain information about alcohol or illicit drug use, and
      history of alcohol-related hospitalization or trouble at work because of drinking
      by the subject. Data about alcohol use by others living in the same house as the
      subject were also obtained. RESULTS: The risks of homicide and suicide associated
      with alcohol or illicit drug use were elevated, as were the risks of violent
      death associated with several indicators of chronic alcohol abuse. In addition,
      nondrinkers living in a home with alcohol users were at increased risk of
      homicide (odds ratio, 1.7; 95% confidence interval, 0.98-3.0), and non-drug-using
      individuals residing in homes with illicit drug users were at greatly increased
      risk of homicide (odds ratio, 11.3; 95% confidence interval, 4.4-28.8).
      CONCLUSIONS: Alcohol and illicit drug use appear to be associated with an
      increased risk of violent death. The risk of homicide was increased for non
      substance-abusing individuals living in households in which other members abused
      alcohol or drugs. The concept of the individual at risk of homicide should be
      broadened to include not only the abuser but also those who may be at risk
      because of their exposure to others.

PMID- 9268279
TI  - Prevention of Vibrio vulnificus infections. Assessment of regulatory educational
      strategies.
AB  - CONTEXT: Vibrio vulnificus-related disease caused by eating contaminated raw
      oysters prompted California to implement regulatory educational initiatives in
      1991. OBJECTIVE: To assess California guidelines and education efforts with
      regard to the prevention of V. vulnificus infections in Los Angeles County and to
      evaluate compliance with state regulations mandating posting of warning signs
      concerning risks of eating raw oysters. DESIGN: Review of epidemiologic
      investigations of V. vulnificus infections in Los Angeles County between 1993 and
      1995; telephone interviews of patients or surrogates; and a survey of restaurants
      serving raw oysters in Los Angeles County. SETTING: General community. MAIN
      OUTCOME MEASURES: Prior warning of patients and posting of warning signs in
      restaurants. RESULTS: Recent cases of V. vulnificus infections in Los Angeles
      County suggest that a unique, vulnerable group (uninsured Hispanic men with viral
      or alcoholic liver disease) has not been reached through education efforts. Of a
      total of 11 cases, information regarding being warned about the hazard of eating
      raw shellfish was available for 8; of these, only 1 case was reported as having
      been warned, but he had misunderstood the preventive message. Warning signs were
      not posted adequately in more than 50% of restaurants surveyed and one third of
      these establishments had signs in English only. Warnings were never located on
      dining tables and rarely included in menus. CONCLUSION: A more effective strategy
      is required to prevent V.vulnificus infections in Los Angeles County.

PMID- 9268280
TI  - When authorship fails. A proposal to make contributors accountable.
AB  - A published article is the primary means whereby new work is communicated,
      priority is established, and academic promotion is determined. Publication
      depends on trust and requires that authors be held to standards of honesty,
      completeness, and fairness in their reporting, and to accountability for their
      statements. The system of authorship, while appropriate for articles with only 1
      author, has become inappropriate as the average number of authors of an article
      has increased; as the work of coauthors has become more specialized and
      relationships between them have become more complex; and as both credit and, even
      more, responsibility have become obscured and diluted. Credit and accountability
      cannot be assessed unless the contributions of those named as authors are
      disclosed to readers, so the system is flawed. We argue for a radical conceptual
      and systematic change, to reflect the realities of multiple authorship and to
      buttress accountability. We propose dropping the outmoded notion of author in
      favor of the more useful and realistic one of contributor. This requires
      disclosure to readers of the contributions made to the research and to the
      manuscript by the contributors, so that they can accept both credit and
      responsibility. In addition, certain named contributors take on the role of
      guarantor for the integrity of the entire work. The requirement that all
      participants be named as contributors will eliminate the artificial distinction
      between authors and acknowledgees and will enhance the integrity of publication.

PMID- 9268281
TI  - Is this patient pregnant? Can you reliably rule in or rule out early pregnancy by
      clinical examination? .
AB  - This review addresses a common problem facing the clinician: "When treating or
      evaluating a woman of childbearing years, what is the value of historical or
      physical examination features in determining the probability of early pregnancy?"
      We focus on the clinical examination findings that may help the clinician rule in
      or rule out early pregnancy. Generally accepted indicators of pregnancy include
      amenorrhea, morning sickness, tender or tingling breasts, and, after 8 weeks'
      gestational age, an enlarged uterus with a soft cervix. We reviewed the value
      (ie, sensitivity and specificity) of these indicators, as well as home pregnancy
      test results, as predictors of the diagnosis of early pregnancy. The available
      evidence suggests that some historical features, when absent, are fair but not
      reliable for ruling out pregnancy. When diagnosing early pregnancy, the clinician
      should not rely on the clinical examination or a home pregnancy test-a laboratory
      test should be requested.

PMID- 9268282
TI  - Pain management and chemical dependency. Evolving perspectives.

PMID- 9268284
TI  - Preventing falls in the nursing home.

PMID- 9268283
TI  - Chronic arthropathy after rubella vaccination in women. False alarm?

PMID- 9268285
TI  - A population-based study of hospitalized injuries in Kingston, Ontario,
      identified via the Canadian Hospitals Injury Reporting and Prevention Program.
AB  - This report uses data from the Kingston and Region Injury Surveillance Program
      (KRISP), a subset of the Canadian Hospitals Injury Reporting and Prevention
      Program (CHIRPP), to describe rates and identify patterns of hospitalized injury
      in Kingston and area. During 1994 and 1995, there were 998 reported
      hospitalizations for injury, resulting in an overall rate of 30.0 injuries per
      10,000 per year (males: 30.3 per 10,000; females: 29.7 per 10,000). Major
      patterns of hospitalized injury were identified as priorities for intervention:
      1) falls in all age groups, but especially those in children, and falls leading
      to hip and pelvic fractures among older adults, the majority of which occurred in
      residential settings; 2) motor vehicle and other transport injuries (e.g.
      motorcycle injuries) in all age groups; and 3) intentional injuries (e.g. fights)
      among males aged 20 64 years. Discussion focuses on the use of the surveillance
      system to set priorities for prevention and further research within this
      population.

PMID- 9268286
TI  - Canadian health surveys, 1950 1997.
AB  - This paper provides a brief history of Canadian health surveys and a review of
      health or health-related surveys from the first national household survey in
      1950/51 to the present time. Surveys have evolved from collecting information on
      health care utilization, health status and some risk behaviours to a wider range
      of health determinants following the 1974 Lalonde report. In addition to the
      occasional cross-sectional surveys, there are periodic surveys, longitudinal
      surveys, school-based surveys and surveys based on subgroups in the population or
      specific topic areas. The survey review is presented in the following four
      tables: Table 1 summarizes national surveys including such information as the
      date(s) and frequency of data collection, topic areas, target population, sample
      size and response rate for each survey; Table 2 provides the same information for
      provincial surveys; both tables point to Table 3, which supplements the previous
      information with survey sponsors and contacts; Table 4 provides similar
      information for commercial surveys. This reference, which will be updated
      periodically, is intended to act as a source of information and support in the
      development of new surveys.

PMID- 9268287
TI  - Fact sheet: major causes of death in Canada, 1993-1995.
AB  - Mortality is one of many summary indicators of disease burden. The following
      tables and graphs display the relative contributions and geographic variability
      of major conditions causing mortality in Canada. Rates are age-standardized to
      permit comparison of the relative impact of different conditions in populations
      with differing age structures. Identifying such geographic variation can help
      generate hypotheses about explanations for these differences and identify areas
      for further investigation. It can also contribute to an estimate of the scope for
      prevention and provide realistic and achievable targets for programs and policies
      intended to reduce disease burden, in that the lowest rate seen for each
      condition is clearly achievable under current Canadian conditions.

PMID- 9268288
TI  - Unconventional cancer therapies.

PMID- 9268289
TI  - Translational regulation of yeast GCN4. A window on factors that control
      initiator-trna binding to the ribosome.

PMID- 9268290
TI  - Yeast Rad7-Rad16 complex, specific for the nucleotide excision repair of the
      nontranscribed DNA strand, is an ATP-dependent DNA damage sensor.
AB  - In eukaryotes, nucleotide excision repair of ultraviolet light-damaged DNA is a
      highly intricate process that requires a large number of evolutionarily conserved
      protein factors. Genetic studies in the yeast Saccharomyces cerevisiae have
      indicated a specific role of the RAD7 and RAD16 genes in the repair of
      transcriptionally inactive DNA. Here we show that the RAD7- and RAD16-encoded
      products exist as a complex of 1:1 stoichiometry, exhibiting an apparent
      dissociation constant (Kd) of <4 x 10(-10) M. The Rad7-Rad16 complex has been
      purified to near homogeneity in this study and is shown to bind, in an ATP
      dependent manner and with high specificity, to DNA damaged by ultraviolet light.
      Importantly, inclusion of the Rad7-Rad16 complex in the in vitro nucleotide
      excision repair system that consists entirely of purified components results in a
      marked stimulation of damage specific incision. Thus, Rad7-Rad16 complex is the
      ATP-dependent DNA damage sensor that specifically functions with the ensemble of
      nucleotide excision repair factor (NEF) 1, NEF2, NEF3, and replication protein A
      in the repair of transcriptionally inactive DNA. We name this novel complex of
      Rad7 and Rad16 proteins NEF4.

PMID- 9268291
TI  - Carboxyl-terminal domain of p27Kip1 activates CDC2.
AB  - A variant form of p27 was unexpectedly detected in a synchronized culture of
      NIH3T3 cells treated with serum. The expression levels of this form of p27 which
      lacked its amino (NH2)-terminal region reached maximum during G2/M phase. Since
      the appearance of the NH2-terminal truncated form of p27 coincided with increased
      expression of Cdc2, we hypothesized that p27 may play a role in regulating Cdc2
      catalytic activity. To test this hypothesis, wild type p27, as well as the amino
      terminal (Np27) and carboxyl-terminal (Cp27), were individually expressed,
      purified, and examined for their ability to regulate CDC2 kinase activity in
      vitro. Our data showed that both p27 and Np27 inhibited CDC2 kinase activity.
      However, in marked contrast, Cp27 enhanced the CDC2 kinase activity. In vitro
      kinase assays showed that Cp27 and p27 were phosphorylated by CDC2, whereas Np27
      was not. In addition, we demonstrated that deletion of the putative CDC2
      phosphorylation site in the carboxyl-terminal domain of Cp27 diminished
      activation of CDC2 kinase activity otherwise stimulated by Cp27. A similar
      deletion did not have any effect on the inhibitory function of p27. Together
      these results suggest that the carboxyl-terminal domain of p27 may activate CDC2
      kinase activity in vivo during G2/M and that this effect may be regulated by
      serine/threonine phosphorylation.

PMID- 9268292
TI  - Communication between switch II and switch III of the transducin alpha subunit is
      essential for target activation.
AB  - Comparisons of the tertiary structures of the GDP-bound and guanosine 5'-O
      (thiotriphosphate) (GTPgammaS)-bound forms of the alpha subunit of transducin
      (alphaT) indicate that there are three regions that undergo changes in
      conformation upon alphaT activation. Two of these regions, Switch I and Switch
      II, were originally identified in Ras, while Switch III appears to be unique to
      trimeric GTP-binding proteins (G proteins). We find that replacement of the
      Switch III region (aspartic acid 227 through asparagine 237) with a single
      alanine residue yields an alphaT subunit that fully binds and hydrolyzes GTP but
      no longer stimulates the activity of the cyclic GMP phosphodiesterase (PDE), the
      physiological target for transducin. We also show that changing glutamic acid 232
      of alphaT to a leucine (E232L) had no effect on rhodopsin-stimulated GTP-GDP
      exchange nor on the GTP hydrolytic activity of alphaT. However, the GTPgammaS
      bound form of the alphaTE232L mutant was unable to stimulate the activity of the
      cyclic GMP PDE. The lack of stimulation was not due to an inability of the
      alphaTE232L mutant to bind to the target. Taken together, these results indicate
      that glutamic acid 232 mediates a conformational coupling between Switch II and
      Switch III, which is essential for converting GTP-dependent G protein-target
      interactions into a stimulation of target/effector activity.

PMID- 9268293
TI  - eIF4G dramatically enhances the binding of eIF4E to the mRNA 5'-cap structure.
AB  - The cap structure, m7GpppN, is present at the 5'-end of all eukaryotic cellular
      (except organellar) mRNAs. Initiation of translation is mediated by the
      multisubunit initiation factor eIF4F, which binds the cap structure via its eIF4E
      subunit and facilitates the binding of mRNA to ribosomes. Here, we used
      recombinant proteins to reconstitute the cap recognition activity of eIF4F in
      vitro. We demonstrate that the interaction of eIF4E with the mRNA 5'-cap
      structure is dramatically enhanced by eIF4G, as determined by a UV-induced cross
      linking assay. Furthermore, assembly of the eIF4F complex at the cap structure,
      as well as ATP hydrolysis, is shown to be a requisite for the cross-linking of
      another initiation factor, eIF4B, to the cap structure. In addition, the
      stimulatory effect of eIF4G on the cap recognition of eIF4E is inhibited by the
      translational repressor, 4E-BP1. These results suggest that eIF4E initially
      interacts with the mRNA cap structure as part of the eIF4F complex.

PMID- 9268294
TI  - Phosphorylation of the tumor suppressor adenomatous polyposis coli (APC) by the
      cyclin-dependent kinase p34.
AB  - Mutations in the tumor suppressor gene APC invariably lead to the development of
      colorectal cancer. The vast majority of these mutations are nonsense or
      frameshifts resulting in nonfunctional, truncated APC protein products. Eleven
      cyclin-dependent kinase (CDK) consensus phosphorylation sites have been
      identified in the frequently deleted carboxyl-terminal region of APC; loss of
      these phosphorylation sites by mutation could therefore compromise the ability of
      APC to inhibit cell growth. This report demonstrates that immunoprecipitates of
      full-length, but not truncated, APC protein include a mitosis-specific kinase
      activity in vivo. Biochemical and Western analysis of these immunoprecipitates
      confirms the presence of the CDK p34(cdc2). We also show that APC is a substrate
      for recombinant human p34(cdc2)-cyclin B1. Modification of APC by p34(cdc2)
      implicates phosphorylation as a mechanism for regulating APC function via a link
      to the cell cycle.

PMID- 9268295
TI  - Dual role of a dileucine motif in insulin receptor endocytosis.
AB  - Two leucines (Leu986 and Leu987) have recently been shown to take part in the
      control of human insulin receptor (HIR) internalization (Renfrew-Haft, C.,
      Klausner, R. D., and Taylor, S. I. (1994) J. Biol. Chem. 269, 26286-26294). The
      aim of the present study was to further investigate the exact mechanism of this
      control process. Constitutive and insulin-induced HIR internalizations were
      studied biochemically and morphologically in NIH 3T3 cells overexpressing either
      a double alanine (amino acid residues 986-987) mutant HIR (HIR AA1) or HIR
      truncated at either amino acid residue 981 (HIR Delta981) or 1000 (HIR
      Delta1000). Data collected indicate that: (a) the three mutant HIR show a reduced
      association with microvilli as compared with HIR wild-type; (b) the two receptors
      containing the dileucine motif (HIR WT and HIR Delta1000) show the highest
      propensity to associate with clathrin-coated pits, independently of kinase
      activation; (c) the two receptors lacking the dileucine motif but containing two
      tyrosine-based motifs, previously described as participating in clathrin-coated
      pit segregation, associate with these surface domains with a lower affinity than
      the two others, (d) in the presence of the kinase domain, an unmasking of the
      tyrosine-based motifs mediated by kinase activation is required. These results
      indicate that the dileucine motif is not sufficient by itself, but participates
      in anchoring HIR on microvilli and that another sequence, located downstream from
      position 1000 is crucial for this event. This dileucine motif also plays a role
      in HIR segregation in clathrin-coated pits. This latter function is additive with
      that of the tyrosine-based motifs but the role of the dileucine motif
      predominates. Eventually, the clathrin-coated pit anchoring function of the
      dileucine motif is independent of receptor kinase activation in contrast to the
      tyrosine-based motifs.

PMID- 9268296
TI  - Elimination of all charged residues in the vicinity of the active-site helix of
      the disulfide oxidoreductase DsbA. Influence of electrostatic interactions on
      stability and redox properties.
AB  - Disulfide oxidoreductases are structurally related proteins that share the
      thioredoxin fold and a catalytic disulfide bond that is located at the N terminus
      of an alpha-helix. The different redox potentials of these enzymes varying from 
      270 mV for thioredoxin to -125 mV for DsbA have been attributed to the lowered
      pKa values of their nucleophilic, active-site cysteines and the difference in
      thermodynamic stability between their oxidized and reduced forms
      (DeltaDeltaGox/red). The lowered pKa of the nucleophilic cysteine thiols was
      proposed to result from favorable interactions with the helix dipole and charged
      residues in their vicinity. In this study, we have eliminated all charged
      residues in the neighborhood of the active-site disulfide of DsbA from
      Escherichia coli to analyze their contribution to the physicochemical properties
      of the protein. We show that the conserved charge network among residues Glu24,
      Glu37, and Lys58 stabilizes the oxidized form of DsbA and thus does not cause the
      high redox potential of the enzyme. The pKa values of the nucleophilic cysteine
      (Cys30) and the redox potentials of the DsbA variants E24Q, E37Q, K58M,
      E24Q/K58M, E37Q/K58M, E24Q/E37Q, E24Q/E37Q/K58M, and E24Q/E37Q/E38Q/K58M are
      similar to those of DsbA wild type. The redox potentials of the variants neither
      correlate with the Cys30 pKa values nor with the DeltaDeltaGox/red values,
      demonstrating that the relationship between these parameters is far more complex
      than previously thought.

PMID- 9268297
TI  - New consensus features for tyrosine O-sulfation determined by mutational
      analysis.
AB  - Tyrosine sulfation is an ubiquitous modification of proteins synthesized along
      the secretory pathway. It enhances protein-protein interactions and may be
      necessary for the bioactivity of secreted proteins and peptides. To predict
      tyrosine sulfation, a consensus has been proposed based on sequence comparisons
      of known substrates and on in vitro studies using synthetic peptides. This
      consensus predicts the presence of acidic residues on the amino-terminal side of
      the target tyrosine as the key feature. Using site-directed mutagenesis, we have
      examined the role of residues neighboring the sulfation site of an intact
      protein, human progastrin, in vivo. The results show that the charge of the
      residue in the amino-terminal position (-1) of the tyrosine is critical and can
      be neutral or acidic, whereas a basic residue abolishes sulfation. In addition,
      the degree of sulfation is influenced by the residues in positions -2 and -3.
      Hence, surprisingly a basic residue in position -2 enhances sulfation. Our data
      suggest a considerably broader range of substrates for the tyrosylprotein
      sulfotransferase than hitherto assumed and that the tyrosylprotein
      sulfotransferase is cell-specifically expressed.

PMID- 9268298
TI  - Ent-kaurene synthase from the fungus Phaeosphaeria sp. L487. cDNA isolation,
      characterization, and bacterial expression of a bifunctional diterpene cyclase in
      fungal gibberellin biosynthesis.
AB  - ent-Kaurene is the first cyclic diterpene intermediate of gibberellin
      biosynthesis in both plants and fungi. In plants, ent-kaurene is synthesized from
      geranylgeranyl diphosphate via copalyl diphosphate in a two-step cyclization
      catalyzed by copalyl diphosphate synthase and ent-kaurene synthase. A cell-free
      system of the fungus Phaeosphaeria sp. L487 converted labeled geranylgeranyl
      diphosphate to ent-kaurene. A cDNA fragment, which possibly encodes copalyl
      diphosphate synthase, was isolated by reverse transcription-polymerase chain
      reaction using degenerate primers based on the consensus motifs of plant enzymes.
      Translation of a full-length cDNA sequence isolated from the fungal cDNA library
      revealed an open reading frame for a 106-kDa polypeptide. The deduced amino acid
      sequence shared 24 and 21% identity with maize copalyl diphosphate synthase and
      pumpkin ent-kaurene synthase, respectively. A fusion protein produced by
      expression of the cDNA in Escherichia coli catalyzed the two-step cyclization of
      geranylgeranyl diphosphate to ent-kaurene. Amo-1618 completely inhibited the
      copalyl diphosphate synthase activity of the enzyme at 10(-6) M, whereas it did
      not inhibit the ent-kaurene synthase activity even at 10(-4) M. These results
      indicate that the fungus has a bifunctional diterpene cyclase that can convert
      geranylgeranyl diphosphate into ent-kaurene. They may be separate catalytic sites
      for the two cyclization reactions.

PMID- 9268299
TI  - Structural mapping of the active site specificity determinants of human tissue
      type plasminogen activator. Implications for the design of low molecular weight
      substrates and inhibitors.
AB  - The recent structure determination of the catalytic domain of tissue-type
      plasminogen activator (tPA) suggested residue Arg174 could play a role in P3/P4
      substrate specificity. Six synthetic chromogenic tPA substrates of the type R-Xaa
      Gly-Arg-p-nitroanilide, in which R is an N-terminal protection group, were
      synthesized to test this property. Although changing the residue Xaa (in its L or
      D form) at position P3 from the hydrophobic Phe to an acidic residue, Asp or Glu,
      gave no improvement in catalytic efficiency, comparative analysis of the
      substrates indicated a preference for an acidic substituent occupying the S3 site
      when the S4 site contains a hydrophobic or basic moiety. The 2.9 A structure
      determination of the catalytic domain of human tPA in complex with the bis
      benzamidine inhibitor 2, 7-bis-(4-amidinobenzylidene)-cycloheptan-1-one reveals a
      three-site interaction, salt bridge formation of the proximal amidino group of
      the inhibitor with Asp189 in the primary specificity pocket, extensive
      hydrophobic surface burial, and a weak electrostatic interaction between the
      distal amidino group of the inhibitor and two carbonyl oxygens of the protein.
      The latter position was previously occupied by the guanidino group of Arg174,
      which swings out to form the western edge of the S3 pocket. These data suggest
      that the side chain of Arg174 is flexible, and does not play a major role in the
      S4 specificity of tPA. On the other hand, this residue would modulate S3
      specificity, and may be exploited to fine tune the specificity and selectivity of
      tPA substrates and inhibitors.

PMID- 9268300
TI  - Probing the interactions of putidaredoxin with redox partners in camphor P450 5
      monooxygenase by mutagenesis of surface residues.
AB  - The role of surface amino acid residues in the interaction of putidaredoxin (Pdx)
      with its redox partners in the cytochrome P450cam (CYP101) system was
      investigated by site-directed mutagenesis. The mutated Pdx genes were expressed
      in Escherichia coli, and the proteins were purified and studied in vitro.
      Activity of the complete reconstituted P450cam system was measured, and kinetic
      parameters were determined. Partial assays were also conducted to determine the
      effect of the mutations on interactions with each redox partner. Some mutations
      altered interactions of Pdx with one redox partner but not the other. Other
      mutations affected interactions with both redox partners, suggesting some overlap
      in the binding sites on Pdx for putidaredoxin reductase and CYP101. Cysteine 73
      of Pdx was identified as important in the interaction of Pdx with putidaredoxin
      reductase, whereas aspartate 38 serves a critical role in the subunit binding and
      electron transfer to CYP101.

PMID- 9268301
TI  - Dissection of pathways implicated in integrin-mediated actin cytoskeleton
      assembly. Involvement of protein kinase C, Rho GTPase, and tyrosine
      phosphorylation.
AB  - A panel of antibodies to the alphaIIbbeta3 integrin was used to promote adhesion
      of Chinese hamster ovary cells transfected with the alphaIIbbeta3 fibrinogen
      receptor. While some alphaIIbbeta3 antibodies were not able to induce p125 focal
      adhesion kinase (p125FAK) tyrosine phosphorylation, all the antibodies equally
      support cell adhesion but not spreading and assembly of actin stress fibers.
      Absence of stress fibers was also obtained by plating on antibodies directed to
      the hamster beta1 integrin. In contrast, cells plated on matrix proteins spread
      organizing actin stress fibers. Treatment with phorbol esters phorbol 12
      myristate 13-acetate (PMA) induced cells to spread on antibodies-coated dishes
      but not to organize actin in stress fibers. The combination of PMA and cytotoxic
      necrotizing factor 1 (CNF1), a specific Rho activator, induced cell spreading and
      organization of stress fibers. PMA or the combination of PMA and CNF1 also
      increases tyrosine phosphorylation of p125FAK in response to antibodies that were
      otherwise unable to trigger this response. These data show that: 1) matrix
      proteins and antibodies differ in their ability to induce integrin-dependent
      actin cytoskeleton organization (while matrix induced stress fibers formation,
      antibodies did not); 2) p125FAK tyrosine phosphorylation is insufficient per se
      to trigger actin stress fibers formation since antibodies that activate p125FAK
      tyrosine phosphorylation did not lead to actin stress fibers assembly; and 3) the
      inability of anti-integrin antibodies to trigger stress fibers organization is
      overcome by concomitant activation of the protein kinase C (PKC) and Rho
      pathways; PKC activation leads to cell spreading and Rho activation is required
      to organize actin stress fibers.

PMID- 9268302
TI  - TLiSA1 (PTA1) activation antigen implicated in T cell differentiation and
      platelet activation is a member of the immunoglobulin superfamily exhibiting
      distinctive regulation of expression.
AB  - T lineage-specific activation antigen 1 (TLiSA1) antigen was initially described
      as a T lineage-specific activation antigen involved in the differentiation of
      human cytotoxic T cells. Subsequently, the antigen was identified on platelets
      and was shown to be involved in platelet activation, hence it was renamed
      platelet and T cell antigen 1 (PTA1), although identity between the two antigens
      was not established. In the present study we have cloned the cDNA encoding TLiSA1
      from Jurkat cells and show it to be a novel member of the immunoglobulin
      superfamily with the unusual structure of two V domains only. Identity between
      TLiSA1 and platelet PTA1 is established by immunological criteria, by internal
      peptide sequences obtained from the purified platelet glycoprotein and by
      sequencing the platelet transcript after reverse transcriptase-polymerase chain
      reaction. In Jurkat cells, TLiSA1/PTA1 mRNA and surface protein expression is
      greatly stimulated by treatment of the cells with phorbol ester, but the T cell
      proliferative signal of phorbol ester and ionophore combined greatly reduces or
      abrogates this response, and this suppressive effect of the ionophore is not
      reversed by incorporating FK506 to inhibit calcineurin. Together with the known
      signaling role of PTA1, these data substantiate the notion that this molecule is
      implicated in T cell differentiation, perhaps by engagement of an adhesive
      ligand.

PMID- 9268303
TI  - Modulation of opsin apoprotein activity by retinal. Dark activity of rhodopsin
      formed at low temperature.
AB  - The bovine opsin apoprotein activates transducin, although at a much reduced
      level than light-activated rhodopsin (Surya, A., Foster, K., and Knox, B. (1995)
      J. Biol. Chem. 270, 5024-5031). The ability of retinal to modulate opsin
      apoprotein activity was investigated using a guanyl nucleotide exchange assay on
      transducin. 11-cis-Retinal reacted with opsin at 22 degrees C to (a) reform
      pigment having maximal absorbance at 500 nm and (b) reduce opsin activity by
      >80%. Pigment formation also occurred at 0 degrees C with a t1/2 of 260 min.
      However, unlike rhodopsin formed at 22 degrees C (R22), the rhodopsin formed at 0
      degrees C (R0) activated transducin with the same half-saturating concentration
      as opsin in an exhaustive binding assay. Thus, the formation of a protonated
      Schiff base associated with 500 nm absorbance does not by itself lead to the
      inactivation of opsin. The R0 conformation was partially inactivated by
      incubation at 22 degrees C (t1/2 = 61 +/- 9 min), suggesting that it may be an
      intermediate conformation in the regeneration of rhodopsin.

PMID- 9268304
TI  - Endoplasmic reticulum chaperones GRP78 and calreticulin prevent oxidative stress,
      Ca2+ disturbances, and cell death in renal epithelial cells.
AB  - Activation of stress response genes can impart cellular tolerance to
      environmental stress. Iodoacetamide (IDAM) is an alkylating toxicant that up
      regulates expression of hsp70 (Liu, H., Lightfoot, D. L., and Stevens, J. L.
      (1996) J. Biol. Chem. 271, 4805-4812) and grp78 in LLC-PK1 renal epithelial
      cells. Therefore, we used IDAM to determine the role of these genes in tolerance
      to toxic chemicals. Prior heat shock did not protect cells from IDAM but
      pretreatment with trans-4,5-dihydroxy-1,2-dithiane (DTTox), thapsigargin, or
      tunicamycin enhanced expression of the endoplasmic reticulum (ER) chaperones
      GRP78 and GRP94 and rendered cells tolerant to IDAM. Cells expressing a 524-base
      pair antisense grp78 fragment (pkASgrp78) had a diminished capacity to up
      regulate grp78 and grp94 expression after ER stress. Protection against IDAM due
      to prior ER stress was also attenuated in pkASgrp78 cells suggesting that ER
      chaperones of the GRP family are critical for tolerance. Covalent binding of IDAM
      to cellular macromolecules and depletion of cellular thiols was similar in
      tolerant and naive cells. However, DTTox pretreatment blocked the increases in
      cellular Ca2+ and lipid peroxidation observed after IDAM treatment.
      Overexpressing the ER Ca2+-binding protein calreticulin prevented IDAM-induced
      cell death, the rise in cytosolic Ca2+, and oxidative stress. Although activation
      of the ER stress response did not prevent toxicity due to Ca2+ influx, EGTA-AM
      and ruthenium red both blocked cell death suggesting that redistribution of
      intracellular Ca2+ to the mitochondria may be important in toxicity. The data
      support a model in which induction of ER stress proteins prevents disturbances of
      intracellular Ca2+ homeostasis, thus uncoupling toxicant exposure from oxidative
      stress and cell death. Multiple ER stress proteins are likely to be involved in
      this tolerance response.

PMID- 9268305
TI  - Reduction of trans-4,5-dihydroxy-1,2-dithiane by cellular oxidoreductases
      activates gadd153/chop and grp78 transcription and induces cellular tolerance in
      kidney epithelial cells.
AB  - trans-4,5-Dihydroxy-1,2-dithiane, the intramolecular disulfide form of
      dithiothreitol (DTTox) transcriptionally activates the stress-responsive genes
      gadd153(chop) and grp78. Herein, we used a renal epithelial cell line, LLC-PK1,
      to investigate the mechanism(s) whereby DTTox activates a molecular stress
      response. DTTox activated both grp78 and gadd153 transcriptionally, but gadd153
      mRNA stability also increased suggesting that both transcriptional and
      posttranscriptional mechanisms are involved. DTTox did not activate hsp70
      transcription indicating that a heat shock response was not induced. Structure
      activity studies showed that DTTox analogues lacking the intramolecular disulfide
      were inactive. Furthermore, the ring-open intermolecular disulfide form of DTTox,
      2-hydroxyethyl disulfide, was only a weak inducer of grp78 and gadd153 but was a
      strong inducer of hsp70 mRNA and a potent oxidant that lowered the NADPH/NADP+
      ratio and depleted reduced glutathione (GSH). DTTox had little effect on the
      overall GSH and NADPH levels; thus cells were not undergoing oxidative stress;
      however, the NADPH/NADP+ ratio decreased slightly indicating that reducing
      equivalents were consumed. LLC-PK1 cells reduced DTTox to DTT, and the kinetics
      as well as the concentration dependence for reduction correlated with induction
      of both grp78 and gadd153 mRNA. Prior treatment with DTTox rendered cells
      tolerant to the potent nephrotoxicant S-(1,1,2, 2-tetrafluoroethyl)-L-cysteine.
      Bacitracin, an inhibitor of plasma membrane oxidoreductases, blocked DTTox
      reduction and gene activation as well as DTTox-induced tolerance. Thus,
      activation of stress genes and induction of cellular tolerance by DTTox is
      mediated by a novel mechanism involving cellular oxidoreductases.

PMID- 9268306
TI  - Inhibition of glutathione reductase by dinitrosyl-iron-dithiolate complex.
AB  - The biological signal molecule nitric oxide (NO) exists in a free and carrier
      bound form. Since the structure of the carrier is likely to influence the
      interaction of NO with macromolecular targets, we assessed the interaction of a
      dinitrosyl-iron-dithiolate complex carrying different thiol ligands with
      glutathione reductase. The enzyme was irreversibly inhibited by dinitrosyl-iron
      di-L-cysteine and dinitrosyl-iron-di-glutathione in a concentration- and time
      dependent manner (IC50 30 and 3 microM, respectively). Evaluation of the
      inhibition kinetics according to Kitz-Wilson yielded a Ki of 14 microM, and a k3
      of 1.3 x 10(-3) s-1. A participation of catalytic site thiols in the inhibitory
      mechanism was indicated by the findings that only the NADPH-reduced enzyme was
      inhibited by dinitrosyl-iron complex and that blockade of these thiols by Hg2+
      afforded protection against irreversible inhibition. This inhibition was not
      accompanied by formation of a protein-bound dinitrosyl-iron complex and/or S
      nitrosation of active site thiols (Cys-58 and Cys-63). However, one NO moiety
      exhibiting an acid lability similar to a secondary N-nitrosamine was present per
      mol of inhibited monomeric enzyme. These findings suggest specifically N
      nitrosation of glutathione reductase as a likely mechanism of inhibition elicited
      by dinitrosyl-iron complex and demonstrate in general that structural resemblance
      of an NO carrier with a natural ligand enhances NO+ transfer to the ligand
      binding protein.

PMID- 9268307
TI  - Temporal and subunit-specific modulations of the Rel/NF-kappaB transcription
      factors through CD28 costimulation.
AB  - Stimulation of highly purified primary T lymphocytes through CD2 and CD28
      adhesion molecules induces a long-term proliferation, dependent on persistent
      autocrine secretion of interleukin 2 (IL-2), high and prolonged expression of
      inducible CD25/IL-2 receptor alpha chain (IL-2Ralpha), and secretion of growth
      factors such as the granulocyte-macrophage colony-stimulating factor (GM-CSF).
      CD28 costimulation appears to activate cytokine gene expression through conserved
      kappaB-related CD28 response (CD28RE) or cytokine 1 (CK-1) elements in addition
      to canonical NF-kappaB-binding sites. In this report, we assess: 1) the evolution
      of the expression, over an 8-day time period, of the Rel/NF-kappaB family of
      proteins in costimulated versus TcR/CD3-stimulated primary T cells; 2) the impact
      of changes on the in vitro occupancy of GM-CSF kappaB and CK-1, as well as IL
      2Ralpha kappaB sites; and 3) the differential regulation of newly synthesized p65
      and c-Rel by IkappaB proteins. We show that CD2+CD28 stimulation specifically
      induces, at maximal T cell proliferation phase, sustained nuclear overexpression
      of NFKB2 p52 and c-Rel subunits which might rely on long-lasting processing of
      p100 precursor for p52 and increased neosynthesis of c-Rel. This up-regulation
      correlates with sustained occupancy of GM-CSF kappaB and CK-1 elements by both
      proteins. Conversely, these subunits do not appear to bind to the IL-2Ralpha
      kappaB site. Costimulation, but not TcR/CD3 stimulation, appears supported by
      sustained down-regulation of both IkappaBalpha and -beta regulators. Furthermore,
      contrary to p65, c-Rel appears to display little affinity for p105, p100 and
      IkappaBalpha regulators.

PMID- 9268308
TI  - Monoterpene synthases from grand fir (Abies grandis). cDNA isolation,
      characterization, and functional expression of myrcene synthase, (-)-(4S)
      limonene synthase, and (-)-(1S,5S)-pinene synthase.
AB  - Grand fir (Abies grandis) has been developed as a model system for studying
      defensive oleoresin formation in conifers in response to insect attack or other
      injury. The turpentine fraction of the oleoresin is a complex mixture of
      monoterpene (C10) olefins in which (-)-limonene and (-)-alpha- and (-)-beta
      pinene are prominent components; (-)-limonene and (-)-pinene synthase activities
      are also induced upon stem wounding. A similarity based cloning strategy yielded
      three new cDNA species from a wounded stem cDNA library that appeared to encode
      three distinct monoterpene synthases. After expression in Escherichia coli and
      enzyme assay with geranyl diphosphate as substrate, subsequent analysis of the
      terpene products by chiral phase gas chromatography and mass spectrometry showed
      that these sequences encoded a (-)-limonene synthase, a myrcene synthase, and a (
      )-pinene synthase that produces both alpha-pinene and beta-pinene. In properties
      and reaction stereochemistry, the recombinant enzymes resemble the corresponding
      native monoterpene synthases of wound-induced grand fir stem. The deduced amino
      acid sequences indicated the limonene synthase to be 637 residues in length (73.5
      kDa), the myrcene synthase to be 627 residues in length (72.5 kDa), and the
      pinene synthase to be 628 residues in length (71.5 kDa); all of these monoterpene
      synthases appear to be translated as preproteins bearing an amino-terminal
      plastid targeting sequence. Sequence comparison revealed that these monoterpene
      synthases from grand fir resemble sesquiterpene (C15) synthases and diterpene
      (C20) synthases from conifers more closely than other monoterpene synthases from
      angiosperm species. This similarity between extant monoterpene, sesquiterpene,
      and diterpene synthases of gymnosperms is surprising since functional
      diversification of this enzyme class is assumed to have occurred over 300 million
      years ago. Wound-induced accumulation of transcripts for monoterpene synthases
      was demonstrated by RNA blot hybridization using probes derived from the three
      monoterpene synthase cDNAs. The availability of cDNA species encoding these
      monoterpene synthases will allow an understanding of the regulation of oleoresin
      formation in conifers and will ultimately permit the transgenic manipulation of
      this defensive secretion to enhance resistance to insects. These cDNAs also
      furnish tools for defining structure-function relationships in this group of
      catalysts that generate acyclic, monocyclic, and bicyclic olefin products.

PMID- 9268309
TI  - Topography of the photosystem I core proteins of the cyanobacterium Synechocystis
      sp. PCC 6803.
AB  - PsaA and PsaB are homologous integral membrane proteins that form the
      heterodimeric core of photosystem I. Domain-specific antibodies were generated to
      examine the topography of PsaA and PsaB. The purified photosystem I complexes
      from the wild type strain of Synechocystis sp. PCC 6803 were treated with eight
      proteases to study the accessibility of cleavage sites in PsaA and PsaB.
      Proteolytic fragments were identified using the information from N-terminal amino
      acid sequencing, reactivity to antibodies, apparent mass, and specificity of
      proteases. The extramembrane loops of PsaA and PsaB differed in their
      accessibility to proteases, which indicated the folded structure of the loops or
      their shielding by the small subunits of photosystem I. NaI-treated and mutant
      photosystem I complexes were used to identify the extramembrane loops that were
      exposed in the absence of specific small subunits. The absence of PsaD exposed
      additional proteolytic sites in PsaB, whereas the absence of PsaE exposed sites
      in PsaA. These studies distinguish PsaA and PsaB in the structural model for
      photosystem I that has been proposed on the basis of x-ray diffraction studies
      (Krauss, N., Schubert, W.-D., Klukas, O., Fromme, P., Witt, H. T., and Saenger,
      W. (1996) Nat. Struct. Biol. 3, 965-973). Using osmotically shocked cells for
      protease treatments, the N terminus of PsaA was determined to be on the n side of
      the photosynthetic membranes. Based on these data and available published
      information, we propose a topological model for PsaA and PsaB.

PMID- 9268310
TI  - Specific deactivation of the mouse mammary tumor virus long terminal repeat
      promoter upon continuous hormone treatment.
AB  - We have studied the transcriptional behavior of the mouse mammary tumor virus
      long repeat (MMTV-LTR) promoter during a prolonged exposure to glucocorticoids.
      When integrated into XC-derived cells, MMTV-LTR expression reached its maximum
      during the first day of dexamethasone treatment, but longer exposure to the
      hormone resulted in the deactivation of the promoter. In contrast, glucocorticoid
      responsive resident genes or MMTV-based transiently transfected plasmids
      maintained or even increased their mRNA levels during the same period of hormone
      treatment. An integrated chimeric construct containing the hormone-responsive
      elements from MMTV-LTR but in different sequence context became also deactivated
      after a prolonged hormone treatment but with a deactivation kinetics
      significantly slower than constructs containing the entire, chromatin-positioning
      MMTV-LTR sequence. The decrease on MMTV-LTR-driven transcription was concomitant
      with a parallel closure of the MMTV-LTR chromatin and with a decrease in
      glucocorticoid receptor (GR) concentration in the cell. We concluded that the
      chromatin-organized MMTV-LTR promoter is particularly sensitive to any decrease
      on GR levels. We propose that chromatin structure may contribute decisively to
      the differential expression of MMTV-LTR by two mechanisms: limiting MMTV-LTR
      accessibility to activating transcription factors and accelerating its shutting
      down upon a decrease on GR levels.

PMID- 9268311
TI  - Affinity purification and kinetic analysis of mutant forms of yeast NAD+-specific
      isocitrate dehydrogenase.
AB  - Polyhistidine tags were added to the carboxyl termini of the two homologous
      subunits of yeast NAD+-specific isocitrate dehydrogenase (IDH). The tag in either
      the IDH1 or IDH2 subunit permits one-step affinity purification from yeast
      cellular extracts of catalytically active and allosterically responsive
      holoenzyme. This expression system was used to investigate subunit-specific
      contributions of residues with putative functions in adenine nucleotide binding.
      The primary effect of simultaneous replacement of the adjacent Asp-279 and Ile
      280 residues in IDH1 with alanines is a dramatic loss of activation by AMP. In
      contrast, alanine replacement of the homologous Asp-286 and Ile-287 residues in
      IDH2 does not alter the allosteric response to AMP, but produces a 160-fold
      reduction in Vmax due to a 70-fold increase in the S0.5 value for NAD+. These
      results suggest that the targeted aspartate/isoleucine residues may contribute to
      regulator binding in IDH1 and to cofactor binding in IDH2, i.e. that these
      homologous residues are located in regions that have evolved for binding the
      adenine nucleotide components of different ligands. In other mutant enzymes, an
      alanine replacement of Asp-191 in IDH1 eliminates measurable catalytic activity,
      and a similar substitution of the homologous Asp-197 in IDH2 produces pleiotropic
      catalytic effects. A model is presented for the primary function of IDH2 in
      catalysis and of IDH1 in regulation, with crucial roles for these single
      aspartate residues in the communication and functional interdependence of the two
      subunits.

PMID- 9268312
TI  - Borna disease virus P-protein is phosphorylated by protein kinase Cepsilon and
      casein kinase II.
AB  - Borna disease virus (BDV) is a newly classified nonsegmented negative-strand RNA
      virus (order of Mononegavirales) that persistently infects specific brain regions
      and circuits of warm-blooded animals to cause behavioral disturbances. Viruses
      within the order of Mononegavirales have phosphoproteins that typically serve as
      transcription factors and are modulated in functional activity through
      phosphorylation. To identify the kinases involved in BDV phosphoprotein (BDV-P)
      phosphorylation, in vitro phosphorylation assays were performed using recombinant
      phosphoprotein produced in Escherichia coli as substrate and cytoplasmic extracts
      from a rat glioma cell line (C6) or rat brain extracts as sources of kinase
      activity. These experiments revealed that BDV-P was phosphorylated predominantly
      by protein kinase C (PKC) and to a lesser extent by casein kinase II. Partial
      purification of the PKC from rat brain extract suggested that the BDV-P
      phosphorylating kinase is PKCepsilon. A role for PKC phosphorylation in vivo was
      confirmed by using the PKC-specific inhibitor GF109203X. Furthermore, peptide
      mapping studies indicated that BDV-P is phosphorylated at the same sites in vitro
      as it is in vivo. Mutational analysis identified Ser26 and Ser28 as sites for PKC
      phosphorylation and Ser70 and Ser86 as sites for casein kinase II
      phosphorylation. The anatomic distribution of PKCepsilon in the central nervous
      system may have implications for BDV neurotropism and pathogenesis.

PMID- 9268313
TI  - Expression of wild-type and modified proalpha chains of human type I procollagen
      in insect cells leads to the formation of stable [alpha1(I)]2alpha2(I) collagen
      heterotrimers and [alpha1(I)]3 homotrimers but not [alpha2(I)]3 homotrimers.
AB  - Insect cells coinfected with a baculovirus coding for the proalpha1(I) chain of
      human type I procollagen and a double promoter virus coding for the alpha and
      beta subunits of human prolyl 4-hydroxylase produced homotrimeric [proalpha1(I)]3
      procollagen molecules. The use of an additional virus coding for the proalpha2(I)
      chain led to the formation of a heterotrimeric molecule with the correct 2:1
      ratio of proalpha1 to proalpha2 chains of type I procollagen (proalpha1(I) and
      proalpha2(I) chains, respectively), unless the proalpha1(I) chain was expressed
      in a relatively large excess. Replacement of the sequences coding for the signal
      peptide and the N propeptide of the proalpha1(I) chain with those of the
      proalpha1(III) chain increased level of expression of the proalpha1(I) chain,
      whereas no similar effect was found when the corresponding modification was made
      to the virus coding for the proalpha2(I) chain. Molecules containing such
      modified N propeptides were found to be processed at their N terminus more
      rapidly than those containing the wild-type propeptides. The Tm of the type I
      collagen homotrimer was similar to that of the heterotrimer, both values being
      about 42-43 degrees C when determined by circular dichroism. The wild-type
      proalpha2(I) chain formed no homotrimers. Replacement of the C propeptide of the
      proalpha2(I) chain with that of the proalpha1(I) chain or proalpha1 chain of type
      III procollagen (proalpha1(III) chain) led to the formation of homotrimers, but
      the alpha2(I) chains in such molecules were completely digested by pepsin in 1 h
      at 22 degrees C. The data thus suggest that, in addition to control at the level
      of the C propeptide, other restrictions may exist at the level of the collagen
      domain that prevent the formation of stable homotrimeric [proalpha2(I)]3
      molecules in insect cells.

PMID- 9268314
TI  - Feedback regulation of ATP-induced Ca2+ signaling in HL-60 cells is mediated by
      protein kinase A- and C-mediated changes in capacitative Ca2+ entry.
AB  - Extracellular ATP increases intracellular Ca2+ ([Ca2+]i) in HL-60 cells. When
      cells are stimulated with supramaximal concentrations of ATP, although the
      initial [Ca2+]i increase is similar over a range of 30, 100, and 300 microM ATP,
      the rate of the return to basal [Ca2+]i level is faster in cells treated with
      higher concentrations of ATP. This probably results from differences in Ca2+
      influx rather than Ca2+ release, since the influx of the unidirectional Ca2+
      surrogates Ba2+ and Mn2+ also exhibit similar responses. Furthermore, while 300
      microM ATP had an inhibitory effect on the thapsigargin-induced capacitative Ca2+
      entry, 30 microM ATP potentiated the response. However, the inhibitory action of
      300 microM ATP was blocked by protein kinase C (PKC) inhibitors, such as GF
      109203X and chelerythrine, and the potentiating action of 30 microM ATP was
      blocked by protein kinase A (PKA) inhibitors H89 and Rp-cAMPS. The PKC inhibitors
      also slowed the decay rate of the Ca2+ response induced by 300 microM ATP, and
      the PKA inhibitors increased it when induced by 30 microM ATP. In the
      measurements of PKA and PKC activity, 30 microM ATP activates only PKA, while 300
      microM ATP activates both kinases. Taken together, these data suggest that the
      changes in the ATP-induced Ca2+ response result from differential modulation of
      ATP-induced capacitative Ca2+ entry by PKC and PKA in HL-60 cells.

PMID- 9268315
TI  - Heme biosynthesis by the malarial parasite. Import of delta-aminolevulinate
      dehydrase from the host red cell.
AB  - The mouse and human malarial parasites, Plasmodium berghei and Plasmodium
      falciparum, respectively, synthesize heme de novo following the standard pathway
      observed in animals despite the availability of large amounts of heme, derived
      from red cell hemoglobin, which is stored as hemozoin pigment. The enzymes, delta
      aminolevulinate dehydrase (ALAD), coproporphyrinogen oxidase, and ferrochelatase
      are present at strikingly high levels in the P. berghei infected mouse red cell
      in vivo. The isolated parasite has low levels of ALAD and the data clearly
      indicate it to be of red cell origin. The purified enzyme preparations from the
      uninfected red cell and the parasite are identical in kinetic properties, subunit
      molecular weight, cross-reaction with antibodies to the human enzyme, and N
      terminal amino acid sequence. Immunogold electron microscopy of the infected
      culture indicates that the enzyme is present inside the parasite and, therefore,
      is not a contaminant. The parasite derives functional ALAD from the host and the
      enzyme binds specifically to isolated parasite membrane in vitro, suggestive of
      the involvement of a receptor in its translocation into the parasite. While,
      ALAD, coproporphyrinogen oxidase, and ferrochelatase from the parasite and the
      uninfected red cell supernatant have identical subunit molecular weights on SDS
      polyacrylamide gel electrophoresis and show immunological cross-reaction with
      antibodies to the human enzymes, as revealed by Western analysis, the first
      enzyme of the pathway, namely, delta-aminolevulinate synthase (ALAS) in the
      parasite, unlike that of the red cell host, does not cross-react with antibodies
      to the human enzyme. However, ALAS enzyme activity in the parasite is higher than
      that of the infected red cell supernatant. We therefore conclude that the
      parasite, while making its own ALAS, imports ALAD and perhaps most of the other
      enzymes of the pathway from the host to synthesize heme de novo, and this would
      enable it to segregate this heme from the heme derived from red cell hemoglobin
      degradation. ALAS of the parasite and the receptor(s) involved in the
      translocation of the host enzymes into the parasite would be unique drug targets.

PMID- 9268316
TI  - Calpain regulation of cytoskeletal signaling complexes in von Willebrand factor
      stimulated platelets. Distinct roles for glycoprotein Ib-V-IX and glycoprotein
      IIb-IIIa (integrin alphaIIbbeta3) in von Willebrand factor-induced signal
      transduction.
AB  - The adhesion of platelets to sites of vascular injury is critically dependent on
      the binding of subendothelial bound von Willebrand factor (vWf) to the platelet
      surface glycoprotein complexes, GP Ib-V-IX and GP IIb-IIIa (integrin
      alphaIIbbeta3). There is growing evidence that the binding of vWf to these
      receptors is not only essential for stable platelet adhesion but is also
      important for the transduction of activation signals required for changes in
      platelet morphology, granule secretion, and platelet aggregation. In this study
      we have investigated signaling events induced by vWf binding to GP Ib-V-IX in
      both spreading and aggregated platelets. The adhesion of platelets to vWf
      resulted in dramatic actin filament reorganization, as assessed by
      immunofluorescence with fluorescein isothiocyanate-conjugated phalloidin, and the
      cytoskeletal recruitment of various structural proteins (talin and integrin
      alphaIIbbeta3) and signaling enzymes (pp60c-src, focal adhesion kinase (FAK),
      phosphatidylinositol 3-kinase (PI 3-kinase), and protein-tyrosine phosphatase
      (PTP)-1B). Time course experiments in both spreading and aggregated platelets
      revealed that talin, FAK, and PTP-1B were proteolyzed after translocation to the
      cytoskeleton. The proteolysis of these proteins was dependent on the presence of
      extracellular calcium and was specifically inhibited by pretreating platelets
      with the membrane-permeable calpain inhibitors calpeptin, E64d, and MDL 28,170,
      but not with the membrane-impermeable inhibitors leupeptin, E64, and calpastatin.
      The cytoskeletal translocation of signaling enzymes in vWf-stimulated platelets
      was abolished by pretreating platelets with an anti-GP Ib-V-IX antibody but was
      unaffected by blocking ligand binding to integrin alphaIIbbeta3. In contrast,
      calpain activation in vWf-stimulated platelets required ligand binding to both GP
      Ib-V-IX and integrin alphaIIbbeta3. The activation of calpain in both spreading
      and aggregated platelets resulted in a substantial decrease in the level of
      tyrosine phosphorylation of multiple platelet proteins and was associated with a
      50-80% reduction in the amount of cytoskeletal associated talin, integrin
      alphaIIbbeta3, PI 3-kinase, FAK, pp60(c-)src, and PTP-1B. These studies suggest a
      potentially important role for calpain in regulating the formation and/or
      stability of cytoskeletal signaling complexes in vWf-stimulated platelets.
      Furthermore, they demonstrate distinct roles for GP Ib-V-IX and integrin
      alphaIIbbeta3 in vWf-induced signal transduction.

PMID- 9268317
TI  - Identification of the gene encoding the Escherichia coli lipid A 4'-kinase.
      Facile phosphorylation of endotoxin analogs with recombinant LpxK.
AB  - The genes for seven of nine enzymes needed for the biosynthesis of Kdo2-lipid A
      (Re endotoxin) in Escherichia coli have been reported. We have now identified a
      novel gene encoding the lipid A 4'-kinase (the sixth step of the pathway). The 4'
      kinase transfers the gamma-phosphate of ATP to the 4'-position of a
      tetraacyldisaccharide 1-phosphate intermediate (termed DS-1-P) to form
      tetraacyldisaccharide 1,4'-bis-phosphate (lipid IVA). The 4'-phosphate is
      required for the action of distal enzymes, such as Kdo transferase and also
      renders lipid A substructures active as endotoxin antagonists or mimetics.
      Lysates of E. coli generated using individual lambda clones from the ordered
      Kohara library were assayed for overproduction of 4'-kinase. Only one clone,
      [218]E1D1, which directed 2-2.5-fold overproduction, was identified. This
      construct contains 20 kilobase pairs of E. coli DNA from the vicinity of minute
      21. Two genes related to the lipid A system map in this region: msbA, encoding a
      putative translocator, and kdsB, the structural gene for CMP-Kdo synthase. msbA
      forms an operon with a downstream, essential open reading frame of unknown
      function, designated orfE. orfE was cloned into a T7 expression system. Washed
      membranes from cells overexpressing orfE display approximately 2000-fold higher
      specific activity of 4'-kinase than membranes from cells with vector alone.
      Membranes containing recombinant, overexpressed 4'-kinase (but not membranes with
      wild-type kinase levels) efficiently phosphorylate three DS-1-P analogs: 3-aza-DS
      1-P, base-treated DS-1-P, and base-treated 3-aza-DS-1-P. A synthetic hexaacylated
      DS-1-P analog, compound 505, can also be phosphorylated by membranes from the
      overproducer, yielding [4'-32P] lipid A (endotoxin). The overexpressed lipid A 4'
      kinase is very useful for making new 4'-phosphorylated lipid A analogs with
      potential utility as endotoxin mimetics or antagonists. We suggest that orfE is
      the structural gene for the 4'-kinase and that it be redesignated lpxK.

PMID- 9268318
TI  - The amino-terminal 118 amino acids of Escherichia coli trigger factor constitute
      a domain that is necessary and sufficient for binding to ribosomes.
AB  - Escherichia coli trigger factor has prolyl-isomerase and chaperone activities and
      associates with nascent polypeptide chains. Trigger factor has a binding site on
      ribosomes, which is a prerequisite for its efficient association with nascent
      chains and its proposed function as a cotranslational folding catalyst. We set
      out to identify the domain of trigger factor that mediates ribosome binding. Of a
      series of recombinant fragments, the amino-terminal fragments, TF (1-144) and TF
      (1-247), cofractionated with ribosomes from cell extracts and rebound to isolated
      ribosomes in vitro. They competed efficiently with full-length trigger factor for
      stoichiometric binding to a single site on the large ribosomal subunit. However,
      TF (1-144) and TF (1-247) differed from full-length trigger factor in that their
      association with ribosomes was not strengthened by the presence of nascent
      chains, indicating a role for carboxyl-terminal trigger factor segment in sensing
      the translational status. The domain responsible for ribosome binding was further
      investigated by limited proteolysis of recombinant fragments. A stable domain
      comprising the amino-terminal 118 residues was identified that was still capable
      of ribosome binding and thus represents a novel structural and functional element
      of trigger factor.

PMID- 9268319
TI  - Regulation of interferon-alpha responsiveness by the duration of Janus kinase
      activity.
AB  - Daudi B lymphoblastoid cells are highly sensitive to the anti-growth and anti
      viral effects of interferon (IFN). Unlike many cell lines, these cells show
      prolonged transcription of IFN-stimulated genes following treatment with IFN
      alpha. This prolonged response correlated with the continued presence of the
      activated transcription factor, IFN-stimulated gene factor 3 (ISGF3). Pulse-chase
      labeling experiments indicated that the half-life of the phosphorylation of
      signal transducers and activators of transcription (Stat)1 and Stat2 was short
      (<2 h) although the turnover of the proteins themselves was slow (>24 h),
      indicative of a constitutive phosphatase activity. The administration of protein
      tyrosine kinase inhibitors at any time point during IFN stimulation led to rapid
      inhibition of the response, indicating that tyrosine kinase activity was
      continuously required. Catalytic activity of Jak1 and Tyk2 kinases remained
      elevated for prolonged periods following stimulation. Continuous presence of IFN
      alpha was necessary for maintaining prolonged activation of ISGF3 and of Janus
      kinases, an activity that was blocked by antibodies to IFN-alpha or by
      cycloheximide. Conditioned medium of IFN-alpha-stimulated cells was capable of
      stimulating STAT activation in naive cells. Taken together, these results suggest
      that the response to IFN-alpha is controlled by the duration of stimulated Janus
      kinase activity over the background of constitutive dephosphorylation and that
      this response can be sustained by autocrine secretion of IFN-alpha.

PMID- 9268320
TI  - Bcl-2 and the outer mitochondrial membrane in the inactivation of cytochrome c
      during Fas-mediated apoptosis.
AB  - Fas-driven apoptosis in Jurkat cells results in the inactivation of cytochrome c
      with cessation of oxygen consumption. Overexpression of Bcl-2 was found to
      protect against acidification and apoptosis mediated by Fas ligation in these
      cells. Bcl-2 is present in the outer mitochondrial membrane, but the molecular
      mechanism by which it protects cells is unknown. Because Bcl-2 projects into the
      mitochondrial intermembrane space and cytochrome c is located in the
      intermembrane space, we considered the possibility that Bcl-2 might protect
      cytochrome c from inactivation during Fas-mediated apoptosis. The present study
      shows that 1) in Jurkat cells, cytochrome c inactivation during Fas-driven
      apoptosis requires the permeabilization of the outer mitochondrial membrane; and
      2) the post-mitochondrial fraction from CEM cells that overexpress Bcl-2 both
      prevents and reverses cytochrome c inactivation.

PMID- 9268321
TI  - Characterization of the adenosine triphosphatase activity of the periplasmic
      histidine permease, a traffic ATPase (ABC transporter).
AB  - The superfamily of traffic ATPases (ABC transporters) includes bacterial
      periplasmic transport systems (permeases) and eukaryotic transporters. The
      histidine permease of Salmonella typhimurium is composed of a membrane-bound
      complex (HisQMP2) containing four subunits, and of a soluble receptor, the
      histidine-binding protein (HisJ). Transport is energized by ATP. In this article
      the ATPase activity of HisQMP2 has been characterized, using a novel assay that
      is independent of transport. The assay uses Mg2+ ions to permeabilize membrane
      vesicles or proteoliposomes, thus allowing access of ATP to both sides of the
      bilayer. HisQMP2 displays a low level of intrinsic ATPase activity in the absence
      of HisJ; unliganded HisJ stimulates the activity and liganded HisJ stimulates to
      an even higher level. All three levels of activity display positive cooperativity
      for ATP with a Hill coefficient of 2 and a K0. 5 value of 0.6 mM. The activity
      has been characterized with respect to pH, salt, phospholipids, substrate, and
      inhibitor specificity. Free histidine has no effect. The activity is inhibited by
      orthovanadate, but not by N-ethylmaleimide, bafilomycin A1, or ouabain. Several
      nucleotide analogs, ADP, 5'-adenylyl-beta, gamma-imidodiphosphate, adenosine 5'
      (beta,gammaimino)triphosphate, and adenosine 5'-O-(3-thio)triphosphate, inhibit
      the activity. Unliganded HisJ does not compete with liganded HisJ for the
      stimulation of the ATPase activity of HisQMP2.

PMID- 9268322
TI  - Dimer to monomer conversion of the cytochrome b6 f complex. Causes and
      consequences.
AB  - The molecular weight of the cytochrome b6 f complex purified from Chlamydomonas
      reinhardtii thylakoid membranes has been determined by combining velocity
      sedimentation measurements, molecular sieving analyses, and determination of its
      lipid and detergent content. The complex in its enzymatically active form is a
      dimer. Upon incubation in detergent solution, it converts irreversibly into an
      inactive, monomeric form that has lost the Rieske iron-sulfur protein, the b6 f
      associated chlorophyll, and, under certain conditions, the small 32-residue
      subunit PetL. The results are consistent with the view that the dimer is the
      predominant form of the b6f in situ while the monomer observed in detergent
      solution is a breakdown product. Indirect observations suggest that subunit PetL
      plays a role in stabilizing the dimeric state. Delipidation is shown to be a
      critical factor in detergent-induced monomerization.

PMID- 9268323
TI  - On the presence and role of a molecule of chlorophyll a in the cytochrome b6 f
      complex.
AB  - Highly purified preparations of cytochrome b6 f complex from the unicellar
      freshwater alga Chlamydomonas reinhardtii contain about 1 molecule of chlorophyll
      a/cytochrome f. Several lines of evidence indicate that the chlorophyll is an
      authentic component of the complex rather than a contaminant. In particular, (i)
      the stoichiometry is constant; (ii) the chlorophyll is associated with the
      complex at a specific binding site, as evidenced by resonance Raman spectroscopy;
      (iii) it does not originate from free chlorophyll released from thylakoid
      membranes upon solubilization; and (iv) its rate of exchange with free,
      radioactive chlorophyll a is extremely slow (weeks). Some of the putative
      functional roles for a chlorophyll in the b6f complex are experimentally ruled
      out, and its possible evolutionary origin is briefly discussed.

PMID- 9268324
TI  - The small conductance calcium-activated potassium channel regulates ion channel
      expression in C3H10T1/2 cells ectopically expressing the muscle regulatory factor
      MRF4.
AB  - We investigated small conductance (SK) potassium channel-mediated regulation of
      muscle-specific, ion channel functional expression in the C3H10T1/2-MRF4 cell
      model system, a stable fibroblast line ectopically overexpressing the myogenic
      regulatory transcription factor, MRF4. Mitogenic stimulation of C3H10T1/2-MRF4
      cells with basic fibroblast growth factor negatively regulates MRF4
      transcriptional activity, inhibiting myogenesis. Using patch clamp techniques we
      found that mitogenic stimulation of C3H10T1/2-MRF4 cells also up-regulated SK. SK
      is a charybdotoxin-sensitive, apamin-insensitive channel that exerts positive
      proliferative control in fibroblasts. Mitogen withdrawal, which removes negative
      regulation of MRF4 thus initiating myogenesis, also eliminated SK channel
      currents, coincident both with induction of acetylcholine receptor channels, and
      up-regulation of muscle inward rectifier potassium channels. Addition of the SK
      channel blocker charybdotoxin to growth factor-containing culture medium overcame
      basic fibroblast growth factor-induced negative regulation of MRF4, as evidenced
      by induction of inward rectifier potassium and acetylcholine receptor channel
      expression identical to that observed in mitogen-withdrawn cells. Thus, the SK
      channel can govern electrophysiological phenotype in C3H10T1/2-MRF4 cells,
      consistent with an ability of SK to affect MRF4-dependent transcriptional
      activity. SK appears to be a pivotal signaling component for growth factor
      regulation of both cell proliferation and differentiation.

PMID- 9268325
TI  - Influence of the positions of cis double bonds in the sn-2-acyl chain of
      phosphatidylethanolamine on the bilayer's melting behavior.
AB  - In an attempt to examine the effects of different numbers and positions of cis
      double bonds in the sn-2-acyl chain of phosphatidylethanolamine (PE) on the
      bilayer's melting behavior, 21 molecular species of PE were first
      semisynthesized, and their Tm and DeltaH values were subsequently determined by
      high resolution differential scanning calorimetry. In the plot of Tm versus the
      number of the cis double bond, some characteristic profiles were observed for the
      various series of PEs. For instance, if the cis double bond was first introduced
      into the sn-2-acyl chain of C(20):C(20)PE at the Delta5-position, the Tm was
      observed to reduce drastically. Subsequent stepwise additions of up to five cis
      double bonds at the methylene-interrupted positions toward the methyl end
      resulted in a progressive yet smaller decrease in Tm. If, on the other hand, the
      cis double bonds were introduced sequentially at the Delta11-, Delta11,14-, and
      Delta11,14,17-positions along the sn-2-acyl chain of C(20):C(20)PE, the Tm
      profile in the Tm versus the number of the cis double bond showed a down-and-up
      trend. Most interestingly, for positional isomers of C(20):C(20:3Delta5,8,11)PE,
      C(20):C(20:3Delta8,11,14)PE, and C(20):C(20:3Delta11,14,17)PE, an inverted bell
      shaped Tm profile was detected in the plot of Tm against the position of the
      omega-carbon for these isomers. Similar Tm profiles were also observed for
      C(18):C(20)PE, C(20):C(18)PE, and their unsaturated derivatives. This work thus
      demonstrated that both the positions and the numbers of cis double bonds in the
      sn-2 acyl chain could exert noticeable influence on the gel-to-liquid crystalline
      phase transition behavior of the lipid bilayer. Finally, a molecular model was
      presented, with which the behavior of the gel-to-liquid crystalline phase
      transition observed for lipid bilayers composed of various sn-1-saturated/sn-2
      unsaturated lipids can be rationalized.

PMID- 9268326
TI  - Xer recombination in Escherichia coli. Site-specific DNA topoisomerase activity
      of the XerC and XerD recombinases.
AB  - Xer site-specific recombination functions in maintaining circular replicons in
      the monomeric state in Escherichia coli. Two recombinases of the bacteriophage
      lambda integrase family, XerC and XerD, are required for recombination at the
      chromosomal site, dif, and at a range of plasmid-borne sites. Xer recombination
      core sites contain the 11-base pair binding sites for each recombinase separated
      by a 6 to 8-base pair central region. We report that both XerC and XerD act as
      site-specific type I topoisomerases by relaxing supercoiled plasmids containing a
      dif site. Relaxation by either XerC or XerD occurs in the absence of the partner
      recombinase and requires only a single recombination core site. XerC or XerD
      relaxation activities are completely inhibited by the addition of the partner
      recombinase, providing that the DNA recognition sequence for the inhibiting
      partner is present.

PMID- 9268327
TI  - Active-site Arg --> Lys substitutions alter reaction and substrate specificity of
      aspartate aminotransferase.
AB  - Arg386 and Arg292 of aspartate aminotransferase bind the alpha and the distal
      carboxylate group, respectively, of dicarboxylic substrates. Their substitution
      with lysine residues markedly decreased aminotransferase activity. The kcat
      values with L-aspartate and 2-oxoglutarate as substrates under steady-state
      conditions at 25 degrees C were 0.5, 2.0, and 0.03 s-1 for the R292K, R386K, and
      R292K/R386K mutations, respectively, kcat of the wild-type enzyme being 220 s-1.
      Longer dicarboxylic substrates did not compensate for the shorter side chain of
      the lysine residues. Consistent with the different roles of Arg292 and Arg386 in
      substrate binding, the effects of their substitution on the activity toward long
      chain monocarboxylic (norleucine/2-oxocaproic acid) and aromatic substrates
      diverged. Whereas the R292K mutation did not impair the aminotransferase activity
      toward these substrates, the effect of the R386K substitution was similar to that
      on the activity toward dicarboxylic substrates. All three mutant enzymes
      catalyzed as side reactions the beta-decarboxylation of L-aspartate and the
      racemization of amino acids at faster rates than the wild-type enzyme. The
      changes in reaction specificity were most pronounced in aspartate
      aminotransferase R292K, which decarboxylated L-aspartate to L-alanine 15 times
      faster (kcat = 0.002 s-1) than the wild-type enzyme. The rates of racemization of
      L-aspartate, L-glutamate, and L-alanine were 3, 5, and 2 times, respectively,
      faster than with the wild-type enzyme. Thus, Arg --> Lys substitutions in the
      active site of aspartate aminotransferase decrease aminotransferase activity but
      increase other pyridoxal 5'-phosphate-dependent catalytic activities. Apparently,
      the reaction specificity of pyridoxal 5'-phosphate-dependent enzymes is not only
      achieved by accelerating the specific reaction but also by preventing potential
      side reactions of the coenzyme substrate adduct.

PMID- 9268328
TI  - Singlet oxygen produced by photodynamic action causes inactivation of the
      mitochondrial permeability transition pore.
AB  - We have studied the effects of singlet oxygen produced by photodynamic action on
      the cyclosporin A-sensitive permeability transition (PT) in isolated rat liver
      mitochondria. Mitochondria were incubated with 3 microM hematoporphyrin and
      irradiated at 365 nm with a fluence rate of 25 watts/m2. For short durations of
      irradiation (60 s) the adenine nucleotide translocase was inactivated, but
      mitochondria retained their ability to form a proton electrochemical gradient and
      accumulated Ca2+ and Pi at the same rate as non-irradiated controls. Strikingly,
      however, the oxidative effects of photodynamic action prevented opening of the PT
      pore which is normally induced by Ca2+ plus Pi or by treatment with diethyl
      pyrocarbonate (a histidine reagent) or diamide (a thiol oxidant). We show that
      the most likely targets for photodynamic action are critical histidines that
      undergo degradation. Irradiated, hematoporphyrin-loaded mitochondria treated with
      diethyl pyrocarbonate or diamide still undergo the PT when treated with
      phenylarsine oxide, which reacts with a critical dithiol involved in pore
      modulation (Petronilli, V., Costantini, P., Scorrano, L., Colonna, R.,
      Passamonti, S., and Bernardi, P. (1994) J. Biol. Chem. 269, 16638-16642). These
      data suggest (i) that the dithiol cysteines are not oxidized by photodynamic
      action, but rather became inaccessible to oxidants; and (ii) that irradiation of
      hematoporphyrin-loaded mitochondria does not lead to pore denaturation, but
      rather to site-selective inactivation of discrete pore functional domains.

PMID- 9268329
TI  - Glucose-dependent liver gene expression in upstream stimulatory factor 2 -/-
      mice.
AB  - Upstream stimulatory factors (USF) 1 and 2 belong to the Myc family of
      transcription factors characterized by a basic/helix loop helix/leucine zipper
      domain responsible for dimerization and DNA binding. These ubiquitous factors
      form homo- and heterodimers and recognize in vitro a CACGTG core sequence termed
      E box. Through binding to E boxes of target genes, USF factors have been
      demonstrated to activate gene transcription and to enhance expression of some
      genes in response to various stimuli. In particular, in the liver USF1 and USF2
      have been shown to bind in vitro glucose/carbohydrate response elements of
      glycolytic and lipogenic genes and have been proposed, from ex vivo experiments,
      to be involved in their transcriptional activation by glucose. However, the
      direct involvement of these factors in gene expression and nutrient gene
      regulation in vivo has not yet been demonstrated. Therefore, to gain insight into
      the specific role of USF1 and USF2 in vivo, and in particular to determine
      whether the USF products are required for the response of genes to glucose, we
      have created, by homologous recombination, USF2 -/- mice. In this paper, we
      provide the first evidence that USF2 proteins are required in vivo for a normal
      transcriptional response of L-type pyruvate kinase and Spot 14 genes to glucose
      in the liver.

PMID- 9268330
TI  - Biphasic binding kinetics between FepA and its ligands.
AB  - The Escherichia coli FepA protein is an energy- and TonB-dependent, ligand
      binding porin that functions as a receptor for the siderophore ferric
      enterobactin and colicins B and D. We characterized the kinetic and thermodynamic
      parameters associated with the initial, energy-independent steps in ligand
      binding to FepA. In vivo experiments produced Kd values of 24, 185, and 560 nM
      for ferric enterobactin, colicin B, and colicin D, respectively. The siderophore
      and colicin B bound to FepA with a 1:1 stoichiometry, but colicin D bound to a
      maximum level that was 3-fold lower. Preincubation with ferric enterobactin
      prevented colicin B binding, and preincubation with colicin B prevented ferric
      enterobactin binding. Colicin B release from FepA was unexpectedly slow in vivo,
      about 10-fold slower than ferric enterobactin release. This slow dissociation of
      the colicin B.FepA complex facilitated the affinity purification of FepA and FepA
      mutants with colicin B-Sepharose. Analysis of a fluorescent FepA derivative
      showed that ferric enterobactin and colicin B adsorbed with biphasic kinetics,
      suggesting that both ligands bind in at least two distinct steps, an initial
      rapid stage and a subsequent slower step, that presumably establishes a transport
      competent complex.

PMID- 9268331
TI  - Role of domains in Escherichia coli and mammalian mitochondrial elongation factor
      Ts in the interaction with elongation factor Tu.
AB  - Bovine mitochondrial elongation factor Ts (EF-Tsmt) stimulates the activity of
      Escherichia coli elongation factor Tu (EF-Tu). In contrast, E. coli EF-Ts is
      unable to stimulate mitochondrial EF-Tu. EF-Tsmt forms a tight complex with E.
      coli EF-Tu governed by an association constant of 8.6 x 10(10). This value is 100
      fold stronger than the binding constant for the formation of the E. coli EF-Tu.Ts
      complex. To test which domain of EF-Tsmt is important for its strong binding with
      EF-Tu, chimeras were made between E. coli EF-Ts and EF-Tsmt. Replacing the N
      terminal domain of E. coli EF-Ts with that of EF-Tsmt increases its binding to E.
      coli EF-Tu 2-3-fold. Replacing the N-terminal domain of EF-Tsmt with the
      corresponding region of E. coli EF-Ts decreases its binding to E. coli EF-Tu
      approximately 4-5-fold. A chimera consisting of the C-terminal half of E. coli EF
      Ts and the N-terminal half of EF-Tsmt binds to E. coli EF-Tu as strongly as EF
      Tsmt. A chimera in which Subdomain N of the core of EF-Ts is replaced by the
      corresponding region of EF-Tsmt binds E. coli EF-Tu approximately 25-fold more
      tightly than E. coli EF-Ts. Thus, the higher strength of the interaction between
      EF-Tsmt and EF-Tu can be localized primarily to a single subdomain.

PMID- 9268332
TI  - Use of fluorescence probes to monitor function of the subunit proteins of the
      MexA-MexB-oprM drug extrusion machinery in Pseudomonas aeruginosa.
AB  - The MexA-MexB-OprM efflux pump of Pseudomonas aeruginosa consists of two inner
      membrane proteins, MexA and MexB, and one outer membrane protein, OprM. We
      investigated the role of the components of this drug extrusion system by
      evaluating the repercussions of deleting these subunit components on the
      accumulation of several fluorescent probes. Fluorescence intensities of
      positively charged 2-(4-dimethylaminostyryl)-1ethylpyridinium and uncharged N
      phenyl-1-naphtylamine were 7 and 4 times higher, respectively, in the mutant
      lacking OprM and 4 and 1.7 times higher, respectively, in the mutants lacking
      MexA or MexB than in the wild type strain. This order of fluorescence intensity
      was fully consistent with a previously reported minimum inhibitory concentration
      of antibiotics such as tetracycline, chloramphenicol, and fluoroquinolones.
      Ethidium bromide accumulation in all the Mex mutants proceeded at about 5 times
      faster than the rate in the wild type cells. This result is in accord with the
      minimum inhibitory concentration of beta-lactam antibiotics. These results
      suggest that the fluorescence probes could be successfully used in real time
      monitoring of the function of the drug extrusion machinery in Gram-negative
      bacteria. The downhill extrusion kinetics of 1-(4-trimethylammoniumphenyl)-6
      phenyl-1,3,5-hexatriene, which orients perpendicular to the inner leaflet of the
      cytoplasmic membrane, from preloaded cells lacking the extrusion pump was
      preceded by a slow increase in fluorescence intensity, whereas the wild type cell
      immediately released the dye. This observation was explained by a slow trans
      cytoplasmic membrane crossing of intracellular dye in the mutants. These results
      reflected higher accumulation of the probe in the cytoplasmic membrane in the
      mutants and strengthened the hypothesis that extrusion of hydrophobic substrate
      mediated by MexA-MexB-OprM mainly takes place from the interior of the
      cytoplasmic membrane.

PMID- 9268333
TI  - Hepatocellular ATP-binding cassette protein expression enhances ATP release and
      autocrine regulation of cell volume.
AB  - In a model liver cell line, recovery from swelling is mediated by a sensitive
      autocrine pathway involving conductive release of ATP, P2 receptor stimulation,
      and opening of membrane Cl- channels (Wang, Y., Roman, R. M., Lidofsky, S. D.,
      and Fitz, J. G. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 12020-12025). However,
      the mechanisms coupling changes in cell volume to ATP release are not known.
      Based on evidence that certain ATP-binding cassette (ABC) proteins may function
      as ATP channels or channel regulators, we evaluated the potential role of ABC
      proteins by comparing ATP release and volume regulation in rat HTC and HTC-R
      hepatoma cells, the latter of which overexpress Mdr proteins. In both cell types,
      Cl- current activation (ICl-swell) and volume recovery following swelling were
      dependent on conductive ATP efflux. The rate of volume recovery was approximately
      6-fold faster in HTC-R cells compared with HTC cells. This effect is likely due
      to enhanced ABC protein-dependent ATP release since (i) ICl-swell and cell volume
      recovery were eliminated by inhibition of P-glycoprotein transport (20 microM
      verapamil and 15 microM cyclosporin A); (ii) swelling-induced Cl- current density
      was similar in both cell types (approximately -50 pA/pF; not significant); and
      (iii) ATP conductance measured by whole-cell techniques was increased
      approximately 3-fold in HTC-R cells compared with HTC cells. Moreover, HTC-R
      cells exhibited enhanced survival during hypotonic stress. By modulating ATP
      release, hepatic ABC proteins may play a key role in the cellular pathways
      coupling changes in cell volume to ion permeability and secretion.

PMID- 9268334
TI  - Expression, purification, and characterization of inosine 5'-monophosphate
      dehydrogenase from Borrelia burgdorferi.
AB  - Inosine 5'-monophosphate dehydrogenase (IMPDH) is the rate-limiting enzyme in de
      novo guanine nucleotide biosynthesis. IMPDH converts IMP to xanthosine 5'
      monophosphate with concomitant conversion of NAD+ to NADH. All IMPDHs
      characterized to date contain a 130-residue "subdomain" that extends from an N
      terminal loop of the alpha/beta barrel domain. The role of this subdomain is
      unknown. An IMPDH homolog has been cloned from Borrelia burgdorferi, the
      causative agent of Lyme disease (Margolis, N., Hogan, D., Tilly, K., and Rosa, P.
      A. (1994) J. Bacteriol. 176, 6427-6432). This homolog has replaced the subdomain
      with a 50-residue segment of unrelated sequence. We have expressed and
      characterized the B. burgdorferi IMPDH homolog. This protein has IMPDH activity,
      which unequivocally demonstrates that the subdomain is not required for catalytic
      activity. The monovalent cation and dinucleotide binding sites of B. burgdorferi
      IMPDH are significantly different from those of human IMPDH. Therefore, these
      sites are targets for the design of specific inhibitors for B. burgdorferi IMPDH.
      Such inhibitors might be new treatments for Lyme disease.

PMID- 9268335
TI  - Rem is a new member of the Rad- and Gem/Kir Ras-related GTP-binding protein
      family repressed by lipopolysaccharide stimulation.
AB  - We report the cDNA cloning and characterization of a novel GTP-binding protein,
      termed Rem (for Rad and Gem-related), that was identified as a product of
      polymerase chain reaction amplification using oligonucleotide primers derived
      from conserved regions of the Rad, Gem, and Kir Ras subfamily. Alignment of the
      full-length open reading frame of mouse Rem revealed the encoded protein to be
      47% identical to the Rad, Gem, and Kir proteins. The distinct structural features
      of the Rad, Gem, and Kir subfamily are maintained including a series of
      nonconservative amino acid substitutions at positions important for GTPase
      activity and a unique sequence motif thought to direct membrane association.
      Recombinant Rem binds GTP in a specific and saturable manner. Ribonuclease
      protection analysis found Rem to be expressed at comparatively high levels in
      cardiac muscle and at moderate levels in lung, skeletal muscle, and kidney. The
      administration of lipopolysaccharide to mice, a potent activator of the
      inflammatory and immune systems, results in the general repression of Rem mRNA
      levels in a dose- and time-dependent manner. Thus, Rem is the first Ras-related
      gene whose mRNA levels have been shown to be regulated by repression.

PMID- 9268336
TI  - Formation of 2',3'-cyclic phosphates at the 3' end of human U6 small nuclear RNA
      in vitro. Identification of 2',3'-cyclic phosphates at the 3' ends of human
      signal recognition particle and mitochondrial RNA processing RNAs.
AB  - Approximately 90% of human U6 small nuclear RNA (snRNA) contains uridine cyclic
      phosphate (U>p) at its 3'-end (Lund, E., and Dahlberg, J. E. (1992) Science 255,
      327-330). We studied the formation of U>p at the 3' end of human U6 snRNA using
      an in vitro system where uridylic acid residues are added from UTP precursor and
      U>p is formed. Analysis of U6 snRNAs with varying number of uridylic acid
      residues showed that each of these species contains U>p where the phosphate
      originated from alpha-phosphate of UTP precursor. The cyclic phosphate formation
      occurred on U6 snRNA in extracts where essential spliceosomal snRNAs were
      specifically degraded, thereby indicating that U>p formation is not coupled to
      pre-mRNA splicing. A subpopulation of human signal recognition particle and
      mitochondrial RNA processing RNAs isolated from HeLa cells also contained cyclic
      phosphates at their 3' ends. These data suggest that U>p in U6 snRNA is unlikely
      to be related to its participation in splicing of pre-mRNAs. It appears that
      cyclic phosphate is an intermediate product in the metabolism of these small
      RNAs.

PMID- 9268337
TI  - Significance of individual point mutations, T202C and C314T, in the human Lewis
      (FUT3) gene for expression of Lewis antigens by the human alpha(1,3/1,4)
      fucosyltransferase, Fuc-TIII.
AB  - The Lewis alpha(1,3/1,4)-fucosyltransferase, Fuc-TIII, encoded by the FUT3 gene
      is responsible for the final synthesis of Lea and Leb antigens. Various point
      mutations have been described explaining the Lewis negative phenotype, Le(a-b-),
      on erythrocytes and secretions. Two of these, T202C and C314T originally
      described in a Swedish population, have not been found as single isolated point
      mutations so far. To define the relative contribution of each of these two
      mutations to the Lewis negative phenotype, we cloned and made chimeric FUT3
      constructs separating the T202C mutation responsible for the amino acid change
      Trp68 --> Arg, from the C314T mutation leading to the Thr105 --> Met shift. COS-7
      cells were transfected and the expression of Fuc-TIII enzyme activity and the
      presence of Lewis antigens were determined. There was no decrease in enzyme
      activity nor of immunofluorescence staining on cells transfected with the
      construct containing the isolated C314T mutation compared with cells transfected
      with a wild type FUT3 allele control. No enzyme activity nor immunoreactivity for
      Lewis antigens was detected in FUT3 constructs containing both mutations in
      combination. The T202C mutation alone decreased the enzyme activity to less than
      1% of the activity of the wild type FUT3 allele. These results demonstrate, that
      the Trp68 --> Arg substitution in human Fuc-TIII is the capital amino acid change
      responsible for the appearance of the Le(a-b-) phenotype on human erythrocytes in
      individuals homozygous for both the T202C and C314T mutations.

PMID- 9268339
TI  - Oxidation of alpha-meso-formylmesoheme by heme oxygenase. Electronic control of
      the reaction regiospecificity.
AB  - The oxidation of heme to biliverdin IXalpha by heme oxygenase involves
      regiospecific alpha-meso-hydroxylation followed by extrusion of the alpha-meso
      carbon as CO. In an earlier study, enzymatic oxidation of the four meso
      methylmesoheme isomers suggested that the reaction regiospecificity is sensitive
      to the electronic properties of the meso-methyl group (Torpey, J. W., and Ortiz
      de Montellano, P. R. (1996) J. Biol. Chem. 271, 26067-26073), although we could
      not exclude the possibility that the altered reaction regiochemistry was due to
      perturbation of the porphyrin structure by the meso-substituent. To examine this
      possibility, we have synthesized the four meso-formylmesoporphyrin isomers and
      have examined their oxidation by heme oxygenase. The meso-formyl and meso-methyl
      substituents differ in that the former is electron withdrawing and the latter is
      electron donating. In contrast to alpha-meso-methylmesoheme, which is exclusively
      oxidized at the methyl-substituted position, alpha-meso-formylmesoheme is
      exclusively oxidized at a non-formyl-substituted meso-carbon. The finding that
      the methyl and formyl groups channel the reaction regiospecificity in opposite
      directions establishes that the regiochemistry of the heme oxygenase reaction is
      primarily under electronic rather than steric control. It also confirms that the
      oxidation involves electrophilic addition of the oxygen to the porphyrin ring.

PMID- 9268338
TI  - Characterization of the interactions between the small GTPase Cdc42 and its
      GTPase-activating proteins and putative effectors. Comparison of kinetic
      properties of Cdc42 binding to the Cdc42-interactive domains.
AB  - The small GTPase Cdc42 interacts with multiple factors to transduce diverse
      intracellular signals. The factors that preferentially recognize the GTP-bound,
      active state of Cdc42 include a panel of GTPase-activating proteins (GAPs), the
      Cdc42/Rac interactive binding (CRIB) motif-containing molecules, and the RasGAP
      domain containing IQGAP1 and IQGAP2. In the present study, we have determined the
      kinetic parameters underlying the functional interactions between the Cdc42
      binding domains of some of these factors and Cdc42 by monitoring the continuous
      release of gammaPi and have compared the ability of the domains to bind to Cdc42.
      The catalytic efficiencies (Kcat/Km) of the GAP domains of Bcr, 3BP-1, and p190
      on Cdc42 are found to be 60-, 160-, and over 500-fold less than that of Cdc42GAP,
      respectively, and the differences are due, to a large part, to differences in Km.
      The Km values of the GAP domains compare well to the binding affinity to the
      guanylyl imidodiphosphate-bound Cdc42, suggesting a rapid equilibrium reaction
      mechanism. The affinity of the Cdc42-binding domains of the CRIB motif of Wiskott
      Aldrich Syndrome protein and p21(cdc42/rac)-activated kinase 1, and the RasGAP
      related domain of IQGAP1, which all inhibit the intrinsic rate of GTP hydrolysis
      of Cdc42, are found to be 4, 0.7, and 0.08 microM, respectively. These
      quantitative analysis provide insight that Cdc42GAP functions as an effective
      negative regulator of Cdc42 by fast, relatively tight binding to the GTP-bound
      Cdc42, whereas IQGAP1 interacts with Cdc42 as a putative effector with over 10
      fold higher affinity than the CRIB domains and GAPs, and suggest that various
      GAPs and effectors employ distinct mechanism to play roles in Cdc42-mediated
      signaling pathways.

PMID- 9268340
TI  - Kinetic and stoichiometric analysis for the binding of Escherichia coli
      ribonuclease HI to RNA-DNA hybrids using surface plasmon resonance.
AB  - To understand how ribonucleases H recognize RNA-DNA hybrid substrates, we
      analyzed kinetic parameters of binding of Escherichia coli RNase HI to RNA-DNA
      hybrids ranging in length from 18 to 36 base pairs (bp) using surface plasmon
      resonance (BIAcoreTM). The kon and koff values for the binding of the enzyme to
      the 36-bp substrate were 1.5 x 10(6) M-1 s-1 and 3.2 x 10(-2) s-1, respectively.
      Similar values were obtained with the shorter substrates. Using uncleavable 2'-O
      methylated RNA-DNA substrates, values for kon and koff were 2.1 x 10(5) M-1 s-1
      and 1.3 x 10(-1) s-1 in the absence of Mg2+ that were further reduced in the
      presence of Mg2+ to 7.4 x 10(3) M-1 s-1 and 2.6 x 10(-2) s-1. Kinetic parameters
      similar to the wild-type enzyme were obtained using an active-site mutant enzyme,
      Asp134 replaced by Ala, whereas a greatly reduced on-rate was observed for
      another inactive mutant enzyme, in which the basic protrusion is eliminated,
      thereby distinguishing between poor catalysis and inability to bind to the
      substrate. Stoichiometric analyses of RNase HI binding to substrates of 18, 24,
      30, and 36 bp are consistent with previous reports suggesting that RNase HI binds
      to 9-10 bp of RNA-DNA hybrid.

PMID- 9268341
TI  - The isolated RNase H domain of murine leukemia virus reverse transcriptase.
      Retention of activity with concomitant loss of specificity.
AB  - Retroviral RNases H are similar in sequence and structure to Escherichia coli
      RNase HI and yet have differences in substrate specificities, metal ion
      requirements, and specific activities. Separation of reverse transcriptase (RT)
      into polymerase and RNase H domains yields an active RNase H from murine leukemia
      virus (MuLV) but an inactive human immunodeficiency virus (HIV) RNase H. The
      "handle region" present in E. coli RNase HI but absent in HIV RNase H contributes
      to the binding to its substrate and when inserted into HIV RNase H results in an
      active enzyme retaining some degree of specificity. Here, we show MuLV protein
      containing the C-terminal 175 amino acids with its own handle region or that of
      E. coli RNase HI has the same specific activity as the RNase H of RT, retains a
      preference for Mn2+ as the cation required for activity, and has association rate
      (KA) 10% that of E. coli RNase HI. However, with model substrates, specificities
      for removal of the tRNAPro primer and polypurine tract stability are lost,
      indicating specificity of RNase H of MuLV requires the remainder of the RT.
      Differences in KA, while significant, appear insufficient to account for the
      differences in specific activities of the bacterial and viral RNases H.

PMID- 9268342
TI  - Regiospecificity and catalytic triad of lysophospholipase I.
AB  - A 25-kDa murine lysophospholipase (LysoPLA I) has been cloned and expressed, and
      Ser-119 has been shown to be essential for the enzyme activity (Wang, A., Deems,
      R. A., and Dennis, E. A. (1997) J. Biol. Chem. 272, 12723-12729). In the present
      study, we show that LysoPLA I represents a new member of the serine hydrolase
      family with Ser-119, Asp-174, and His-208 composing the catalytic triad. The Asp
      174 and His-208 are conserved among several esterases and are demonstrated herein
      to be essential for LysoPLA I activity as the mutation of either residue to Ala
      abolished LysoPLA I activity, whereas the global conformation of the mutants
      remained unchanged. Furthermore, the predicted secondary structure of LysoPLA I
      resembles that of the alpha/beta-hydrolase fold, with Ser-119, Asp-174, and His
      208 occupying the conserved topological location of the catalytic triad in the
      alpha/beta-hydrolases. Structural modeling of LysoPLA I also indicates that the
      above three residues orient in such a manner that they would comprise a charge
      relay network necessary for catalysis. In addition, the regiospecificity of
      LysoPLA I was studied using 31P NMR, and the result shows that LysoPLA I has
      similar LysoPLA1 and LysoPLA2 activity. This finding suggests that LysoPLA I may
      play an important role in removing lysophospholipids produced by both
      phospholipase A1 and A2 in vivo.

PMID- 9268343
TI  - Interaction of calcium with native and decarboxylated human factor X. Effect of
      proteolysis in the autolysis loop on catalytic efficiency and factor Va binding.
AB  - Human factor X is a two-chain, 58-kDa, vitamin K-dependent blood coagulation
      zymogen. The light chain of factor X consists of an NH2-terminal gamma
      carboxyglutamic acid (Gla) domain, followed by a few helical hydrophobic residues
      and the two epidermal growth factor-like domains, whereas the heavy chain
      contains the serine protease domain. In this study, native factor X was found to
      contain three classes of Ca2+-binding sites: two high affinity (Kd 100 +/- 30
      microM), four intermediate affinity (Kd 450 +/- 70 microM), and five to six low
      affinity (Kd 2 +/- 0.2 mM). Decarboxylated factor X in which the Gla residues
      were converted to Glu retained the two high affinity sites (Kd 140 +/- 20
      microM). In contrast, factor X lacking the Gla domain as well as a part of the
      helical hydrophobic residues (des-44-X) retained only one high affinity Ca2+
      binding site (Kd 130 +/- 20 microM). Moreover, a synthetic peptide composed of
      residues 238-277 (58-97 in chymotrypsinogen numbering) from the protease domain
      of factor X bound one Ca2+ with high affinity (Kd 150 +/- 20 microM). From
      competitive inhibition assays for binding of active site-blocked factor Xa to
      factor Va in the prothrombinase complex, the Kd for peptide-Va interaction was
      calculated to be approximately 10 microM as compared with 30 pM for factor Xa and
      approximately 1.5 microM for decarboxylated factor Xa. A peptide containing
      residues 238-262(58-82) bound Ca2+ with reduced affinity (Kd approximately 600
      microM) and did not inhibit Xa:Va interaction. In contrast, a peptide containing
      residues 253-277(73-97) inhibited Xa:Va interaction (Kd approximately 10 microM)
      but did not bind Ca2+. In additional studies, Ca2+ increased the amidolytic
      activity of native and des-44-Xa toward a tetrapeptide substrate (benzoyl-Ile-Glu
      Gly-Arg-p-nitroanilide) by approximately 1.6-fold. The half-maximal increase was
      observed at approximately 150 microM Ca2+ and the effect was primarily on the
      kcat. Ca2+ also significantly protected cleavage at Arg-332-Gln-333(150-151) in
      the protease domain autolysis loop. Des-44-Xa in which the autolysis loop was
      cleaved possessed </=5% of the amidolytic activity of the noncleaved form;
      however, the S1 binding site was not affected, as determined by the p
      aminobenzamidine binding. Additionally, autolysis loop-cleaved, active site
      blocked native factor Xa was calculated to have approximately 10-fold reduced
      affinity for factor Va as compared with that of the noncleaved form.

PMID- 9268344
TI  - A kinase domain-truncated type I receptor blocks bone morphogenetic protein-2
      induced signal transduction in C2C12 myoblasts.
AB  - Members of the transforming growth factor (TGF)-beta superfamily bind the
      transmembrane serine/threonine kinase complex consisting of type I and type II
      receptors. Their intracellular signals are propagated via respective type I
      receptors. Bone morphogenetic protein (BMP)-2, a member of the TGF-beta
      superfamily, induces ectopic bone formation when implanted into muscular tissues.
      Two type I receptors (BMPR-IA and BMPR-IB) have been identified for BMP-2. We
      have reported that BMP-2 inhibits the terminal differentiation of C2C12 myoblasts
      and converts their differentiation pathway into that of osteoblast lineage cells
      (Katagiri, T., Yamaguchi, A., Komaki, M., Abe, E., Takahashi, N., Ikeda, T.,
      Rosen, V., Wozney, J. M., Fujisawa-Sehara, A. and Suda, T. (1994) J. Cell Biol.
      127, 1755-1766). In the present study, we examined the involvement of functional
      BMP-2 type I receptors in signal transduction in C2C12 cells, which expressed
      mRNA for BMPR-IA, but not for BMPR-IB in Northern blotting. TGF-beta type I
      receptor (TbetaR-I) mRNA was also expressed in C2C12 cells. Subclonal cell lines
      of C2C12 that stably expressed a kinase domain-truncated BMPR-IA (DeltaBMPR-IA)
      differentiated into myosin heavy chain-expressing myotubes but not into alkaline
      phosphatase (ALP)-positive cells, even in the presence of BMP-2. In contrast, the
      differentiation of the DeltaBMPR-IA-transfected C2C12 cells into myotubes was
      suppressed by TGF-beta1, as in the parental C2C12 cells. BMP-2 did not
      efficiently suppress the mRNA expression of muscle-specific genes such as muscle
      creatine kinase, MyoD, and myogenin, nor did it induce the expression of ALP mRNA
      in the DeltaBMPR-IA-transfected C2C12 cells. In contrast, TGF-beta1 inhibited
      mRNA expression of the muscle-specific genes in those cells. When wild-type BMPR
      IA was transiently transfected into the DeltaBMPR-IA-transfected C2C12 cells, a
      number of ALP-positive cells appeared in the presence of BMP-2. Transfection of
      wild-type BMPR-IB or TbetaR-I failed to increase the number of ALP-positive
      cells. These results suggest that the BMP-2-induced signals, which inhibit
      myogenic differentiation and induce osteoblast differentiation, are transduced
      via BMPR-IA in C2C12 myoblasts.

PMID- 9268345
TI  - Initiation of osteoclast bone resorption by interstitial collagenase.
AB  - Osteoclasts form an acidic compartment at their attachment site in which bone
      demineralization and matrix degradation occur. Although both the cysteine
      proteinases and neutral collagenases participate in bone resorption, their roles
      have remained unclear. Here we show that interstitial collagenase has an
      essential role in initiating bone resorption, distinct from that of the cysteine
      proteinases. Treatment of osteoclasts with cysteine proteinase inhibitors did not
      affect the number of resorption lacunae ("pits") formed on the surface of dentine
      slices, but it generated abnormal pits that were demineralized but filled with
      undegraded matrix. Treatment with metalloproteinase inhibitors did not alter the
      qualitative features of lacunae, but it greatly reduced the number of pits and
      surface area resorbed. Treatment of bone cells with an inhibitory anti-rat
      interstitial collagenase antiserum reduced bone resorption markedly. In the
      presence of collagenase inhibitors, resorption was restored by pretreatment of
      dentine slices with rat interstitial collagenase or by precoating the dentine
      slices with collagenase-derived gelatin peptides or heat-gelatinized collagen.
      Immunostaining revealed that interstitial collagenase is produced at high levels
      by stromal cells and osteoblasts adjacent to osteoclasts. These results indicate
      that interstitial collagenase can function as a "coupling factor," allowing
      osteoblasts to initiate bone resorption by generating collagen fragments that
      activate osteoclasts.

PMID- 9268346
TI  - A comparative analysis of the phosphoinositide binding specificity of pleckstrin
      homology domains.
AB  - Pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains are
      structurally related regulatory modules that are present in a variety of proteins
      involved in signal transduction, such as kinases, phospholipases, GTP exchange
      proteins, and adapter proteins. Initially these domains were shown to mediate
      protein-protein interactions, but more recently they were also found to bind
      phosphoinositides. Most studies to date have focused on binding of PH domains to
      phosphatidylinositol (PtdIns)-4-P and PtdIns-4,5-P2 and have not considered the
      lipid products of phosphoinositide 3-kinase: PtdIns-3-P, PtdIns-3,4-P2, and
      PtdIns-3,4,5-P3. Here we have compared the phosphoinositide specificity of six
      different PH domains and the Shc PTB domain using all five phosphoinositides. We
      show that the Bruton's tyrosine kinase PH domain binds to PtdIns-3,4, 5-P3 with
      higher affinity than to PtdIns-4,5-P2, PtdIns-3,4-P2 or inositol 1,3,4,5
      tetrakisphosphate (Ins-1,3,4,5-P4). This selectivity is decreased by the xid
      mutation (R28C). Selective binding of PtdIns-3,4,5-P3 over PtdIns-4,5-P2 or
      PtdIns-3,4-P2 was also observed for the amino-terminal PH domain of T lymphoma
      invasion and metastasis protein (Tiam-1), the PH domains of Son-of-sevenless
      (Sos) and, to a lesser extent, the PH domain of the beta-adrenergic receptor
      kinase. The oxysterol binding protein and beta-spectrin PH domains bound PtdIns
      3,4,5-P3 and PtdIns-4,5-P2 with similar affinities. PtdIns-3,4,5-P3 and PtdIns
      4,5-P2 also bound to the PTB domain of Shc with similar affinities and lipid
      binding was competed with phosphotyrosine (Tyr(P)-containing peptides. These
      results indicate that distinct PH domains select for different phosphoinositides.

PMID- 9268347
TI  - NIPP-1, a nuclear inhibitory subunit of protein phosphatase-1, has RNA-binding
      properties.
AB  - NIPP-1 is a nuclear inhibitory subunit of protein phosphatase-1 with structural
      similarities to some proteins involved in RNA processing. We report here that
      baculovirus-expressed recombinant NIPP-1 displays RNA-binding properties, as
      revealed by North-Western analysis, by UV-mediated cross-linking, by RNA mobility
      shift assays, and by chromatography on poly(U)-Sepharose. NIPP-1 preferentially
      bound to U-rich sequences, including RNA-destabilizing AUUUA motifs. NIPP-1 also
      associated with single-stranded DNA, but had no affinity for double-stranded DNA.
      The binding of NIPP-1 to RNA was blocked by antibodies directed against the COOH
      terminus of NIPP-1, but was not affected by prior phosphorylation of NIPP-1 with
      protein kinase A or casein kinase-2, which decreases the affinity of NIPP-1 for
      protein phosphatase-1. The catalytic subunit of protein phosphatase-1 did not
      bind to poly(U)-Sepharose, but it bound very tightly after complexation with NIPP
      1. These data are in agreement with a function of NIPP-1 in targeting protein
      phosphatase-1 to RNA.

PMID- 9268349
TI  - The role of putative fibrinogen Aalpha-, Bbeta-, and GammaA-chain integrin
      binding sites in endothelial cell-mediated clot retraction.
AB  - In this study, endothelial cell-mediated clot retraction was supported by fibrin
      generated from several purified fractions of plasma fibrinogen, purified
      proteolytic fragments of plasma fibrinogen, recombinant normal fibrinogen, and
      recombinant variant fibrinogen. These results were surprising because some of
      these fibrinogens lack domains that are known binding sites for the integrin
      receptors that support clot retraction. Specifically, fibrinogens lacking Aalpha
      chain RGD residues at 572-574 or lacking the gamma-chain residues AGDV 408-411
      supported endothelial cell-mediated clot retraction as well as intact fibrinogen.
      Thus, clot retraction mediated by endothelial cells is not dependent on either of
      these sites. A variety of monoclonal antibodies against the integrin alphavbeta3
      partially inhibited the endothelial cell-mediated retraction of clots formed from
      plasma fibrinogen. As expected, an antibody to the platelet integrin
      alphaIIbbeta3 did not inhibit endothelial cell-mediated clot retraction. These
      results indicate that this retraction is mediated at least in part by
      alphavbeta3. These results support the conclusion that (a) neither of the two
      fibrinogen cell binding sites described above is required to support clot
      retraction or that (b) either site alone or in conjunction with other
      fibrin(ogen) region(s) can support clot retraction. Thus, endothelial cell
      mediated clot retraction appears to be dependent on fibrinogen cell binding sites
      other than those required to support adhesion of resting platelets to immobilized
      fibrinogen and platelet aggregation.

PMID- 9268348
TI  - Mapping of the primary binding site of measles virus to its receptor CD46.
AB  - The measles virus (MV) hemagglutinin binds to the complement control protein
      (CCP) CD46 primarily through the two external modules, CCP-I and -II. To define
      the residues involved in binding, 40 amino acids predicted to be solvent-exposed
      on the CCP-I-II module surface were changed to either alanine or serine. Altered
      proteins were expressed on the cell surface, and their abilities to bind purified
      MV particles, a soluble form of hemagglutinin (sH) and nine CD46-specific
      antibodies competing to different levels with sH attachment, were measured. All
      proteins retained, at least in part, MV and sH binding, but some completely lost
      binding to certain antibodies. Amino acids essential for binding of antibodies
      weakly or moderately competing with sH attachment are situated in the membrane
      distal tip of CCP-I, whereas residues involved in binding of strongly sH
      competing antibodies cluster in the center of CCP-I (Arg-25, Asp-27) or in CCP-II
      (Arg-69, Asp-70). Both clusters face the same side of CCP-I-II and map close to
      amino acid exchanges impairing sH binding (E11A, R29A, P39A, and D70A) or MV
      binding (D70A and E84A) and to a six-amino acid loop, previously shown to be
      necessary for sH binding.

PMID- 9268350
TI  - Mutational study of the amino-terminal domain of human tissue inhibitor of
      metalloproteinases 1 (TIMP-1) locates an inhibitory region for matrix
      metalloproteinases.
AB  - A bacterial expression system for the inhibitory N-terminal domain of human
      tissue inhibitor of metalloproteinases 1 (N-TIMP-1) (Huang, W., Suzuki, K.,
      Nagase, H., Arumugam, S., Van Doren, S. R., and Brew, K. (1996) FEBS Lett. 384,
      155-161) has been used to produce 20 single- and double-site mutants that probe
      the roles of different residues in its inhibitory action on metalloproteinases.
      Mutations that produce the largest increases in the Ki for a C-terminally
      truncated form of stromelysin 1, MMP-3(DeltaC), but do not disturb the
      conformation involve substitutions of residues that are located in a ridge that
      is centered around the disulfide bond between Cys1 and Cys70. Specific residues
      that have a large influence on activity include Cys1, Thr2, Met66, Val69, and
      Cys70. Of the mutations introduced, the greatest functional disturbances,
      reflected in Ki increases of 2-4 orders of magnitude, are generated by changes
      that disrupt the Cys1-Cys70 disulfide bond and by substitution of Ala for Thr2.
      Most mutations that perturb the interaction with MMP-3 have parallel effects on
      the affinity of N-TIMP-1 for MMP-1 (interstitial collagenase) and MMP-2
      (gelatinase A). However, the Thr2 to Ala mutation produces an inhibitor that is
      17-fold more effective against MMP-3 than MMP-1, suggesting that it is feasible
      to engineer TIMP-1 variants that are more specifically targeted to selected
      matrix metalloproteinases. The reactive site identified by these studies is a
      structurally constrained but elongated region of TIMP that can fit the matrix
      metalloproteinase substrate-binding site.

PMID- 9268351
TI  - Comparison of the DNA association kinetics of the Lac repressor tetramer, its
      dimeric mutant LacIadi, and the native dimeric Gal repressor.
AB  - The rates of association of the tetrameric Lac repressor (LacI), dimeric LacIadi
      (a deletion mutant of LacI), and the native dimeric Gal repressor (GalR) to DNA
      restriction fragments containing a single specific site were investigated using a
      quench-flow DNase I "footprinting" technique. The dimeric proteins, LacIadi and
      GalR, and tetrameric LacI possess one and two DNA binding sites, respectively.
      The nanomolar protein concentrations used in these studies ensured that the state
      of oligomerization of each protein was predominantly either dimeric or
      tetrameric, respectively. The bimolecular association rate constants (ka)
      determined for the LacI tetramer exceed those of the dimeric proteins. The values
      of ka obtained for LacI, LacIadi, and GalR display different dependences on
      [KCl]. For LacIadi and GalR, they diminish as [KCl] increases from 25 mM to 200
      mM, approaching rates predicted for three-dimensional diffusion. In contrast, the
      ka values determined for the tetrameric LacI remain constant up to 300 mM [KCl],
      the highest salt concentration that could be investigated by quench-flow
      footprinting. The enhanced rate of association of the tetramer relative to the
      dimeric proteins can be modeled by enhanced "sliding" (Berg, O. G., Winter, R.
      B., and von Hippel, P. H. (1981) Biochemistry 20, 6929-6948) of the LacI tetramer
      relative to the LacIadi dimer or a combination of enhanced sliding and the
      superimposition of "direct transfer" mediated by the bidentate DNA interactions
      of the tetramer.

PMID- 9268352
TI  - Ricin A chain can transport unfolded dihydrofolate reductase into the cytosol.
AB  - Ricin is a heterodimeric protein toxin. The ricin A chain is able to cross the
      membrane of intracellular compartments to reach the cytosol where it
      catalytically inactivates protein synthesis. It is linked via a disulfide bond to
      the B chain, a galactose-specific lectin, which allows ricin binding at the cell
      surface and endocytosis. To examine the potential of ricin A to carry proteins
      into the cytosol and the requirement for unfolding of the passenger protein, we
      connected mouse dihydrofolate reductase (DHFR) to ricin A by gene fusion via a
      spacer peptide. DHFR-ricin A expressed in Escherichia coli displayed the
      biological activities of the parent proteins and associated quantitatively with
      ricin B to form DHFR-ricin. The resulting toxin was highly cytotoxic to cells (4
      8-fold less than recombinant ricin). DHFR-ricin cytotoxicity was inhibited by
      methotrexate, a DHFR inhibitor stabilizing DHFR-ricin A in a folded conformation.
      The DHFR moiety of DHFR ricin bound to the plasma membrane. Although methotrexate
      prevented this binding, it did not significantly affect DHFR-ricin endocytosis,
      which proceeded via ricin B chain. Intoxication kinetics data and a cell-free
      translocation assay demonstrated that protection of cells from DHFR-ricin
      cytotoxicity resulted from a selective inhibition by methotrexate of DHFR-ricin A
      translocation. We conclude that ricin A is a potential carrier of proteins to the
      cytosol, provided that the passenger protein is able to unfold for transmembrane
      transport.

PMID- 9268353
TI  - Induction and repression of collagenase-1 by keratinocytes is controlled by
      distinct components of different extracellular matrix compartments.
AB  - In all forms of cutaneous wounds, collagenase-1 (matrix metalloproteinase-1 (MMP
      1)) is invariably expressed by basal keratinocytes migrating over the dermal
      matrix. We report that native type I collagen mediates induction of MMP-1 by
      primary human keratinocytes. Collagen-mediated induction of MMP-1 was rapid,
      being detected 2 h after plating, and was transcriptionally regulated. As
      demonstrated by in situ hybridization, only migrating keratinocytes expressed MMP
      1, suggesting that contact with collagen is not sufficient to induce MMP-1
      expression in keratinocytes; the cells must also be migrating. Upon denaturation,
      type I collagen lost its ability to induce MMP-1 expression but still supported
      cell adhesion. Other dermal or wound matrix proteins, such as type III collagen,
      fibrin, and fibronectin, and a mixture of basement membrane proteins did not
      induce MMP-1 production. In the presence of collagen, laminin-1 inhibited
      induction of MMP-1 but laminin-5 did not. Taken together, these observations
      suggest that as basal keratinocytes migrate from the basal lamina onto the dermal
      matrix contact with native type I collagen induces MMP-1 expression. In addition,
      our findings suggest that re-establishment of the basement membrane and, in
      particular, contact with laminin-1 provides a potent signal to down-regulate MMP
      1 production as the epithelium is repaired.

PMID- 9268354
TI  - Covalent antithrombin-heparin complexes with high anticoagulant activity.
      Intravenous, subcutaneous, and intratracheal administration.
AB  - Although heparin has been used clinically for prophylaxis and treatment of
      thrombosis, it has suffered from problems such as short duration within
      compartments in vivo that require long term anticoagulation. A covalent
      antithrombin-heparin complex has been produced with high anticoagulant activity
      and a long half-life relative to heparin. The product had high anti-factor Xa and
      antithrombin activities compared with noncovalent mixtures of antithrombin and
      heparin (861 and 753 units/mg versus 209 and 198 units/mg, respectively).
      Reaction with thrombin was rapid with bimolecular and second order rate constants
      of 1.3 x 10(9) M-1 s-1 and 3.1 x 10(9) M-1 s-1, respectively. The intravenous
      half-life of the complex in rabbits was 2.6 h as compared with 0.32 h for similar
      loads of heparin. Subcutaneous injection of antithrombin-heparin resulted in
      plasma levels (peaking at 24-30 h) that were still detectable 96 h post
      injection. Given the increased lifetime in these vascular and intravascular
      spaces, use of the covalent complex in the lung was investigated. Activity of
      antithrombin-heparin instilled into rabbit lungs remained for 48 h with no
      detection of any complex systemically. Thus, this highly active agent has
      features required for pulmonary sequestration as a possible treatment for
      thrombotic diseases such as respiratory distress syndrome.

PMID- 9268355
TI  - A 32-kDa proteolytic fragment of transcription factor Stat3 is capable of
      specific DNA binding.
AB  - Fragments of characteristic size retaining the ability of sequence-specific DNA
      binding were generated by partial proteolysis of transcription factor Stat3 with
      trypsin, chymotrypsin, or Staphylococcus V8 proteinase. The molecular masses of
      the smallest DNA-binding fragments were 75, 48, and 32 kDa after digestion with
      V8 proteinase, chymotrypsin, and trypsin, respectively. The fragments contained
      major parts of the domain controlling the sequence specificity of DNA binding
      (amino acids 406-514), the SH3 and SH2 domains, and the phosphorylated tyrosine
      residue Tyr-705, but not the C-terminal 20 amino acids. The N terminus of the 32
      kDa tryptic fragment (ANCDASLIV) matched the sequence of amino acids 424-432
      deduced from cDNA. The fragments were observed after proteolytic treatment of
      preformed complexes between DNA and native factors eluted from rat liver nuclei
      or recombinant, tyrosine-phosphorylated rat Stat3 from insect cells. It was
      possible to elute all three minimal fragments from their complexes with DNA and
      to obtain specific re-binding. The minimal fragments eluted from complexes with
      DNA still contained the phosphorylated Tyr-705 and the SH2 domain suggesting that
      they were probably bound to DNA as dimers. The DNA-binding domain of Stat3
      identified by these experiments overlapped the domain previously identified by
      genetic experiments as the domain controlling the sequence specificity of DNA
      binding. The DNA-binding domain defined here by partial proteolysis probably
      represents an autonomously folding portion of Stat3.

PMID- 9268356
TI  - Biochemical characterization and mass spectrometric disulfide bond mapping of
      periplasmic alpha-amylase MalS of Escherichia coli.
AB  - Periplasmic alpha-amylase of Escherichia coli, the malS gene product, hydrolyzes
      linear maltodextrins. The purified enzyme exhibited a Km of 49 microM and a Vmax
      of 0.36 micromol of p-nitrophenylhexaoside hydrolyzed per min per mg of protein.
      Amylase activity was optimal at pH 8 and was dependent on divalent cations such
      as Ca2+. MalS exhibited altered migration on SDS-polyacrylamide gel
      electrophoresis under nonreducing conditions. Analytical ultracentrifugation and
      electrospray mass spectrometry indicated that MalS is monomeric. The four
      cysteine residues are involved in intramolecular disulfide bonds. To map
      disulfide bonds, MalS was proteolytically digested. The resulting peptides were
      separated by reverse phase-high performance liquid chromatography, and matrix
      assisted laser desorption/ionization mass spectrometry analysis indicated the
      presence of two disulfide bonds, i.e. Cys40-58 and Cys104-520. The disulfide bond
      at Cys40-58 is located in an N-terminal extension of about 160 amino acids which
      has no homology to other amylases but to the proposed peptide binding domain of
      GroEL, the Hsp60 of E. coli. The N-terminal extension is linked to the C-terminal
      amylase domain via disulfide bond Cys104-520. Reduction of disulfide bonds by
      dithiothreitol treatment led to aggregation suggesting that the N terminus of
      MalS may represent an internal chaperone domain.

PMID- 9268357
TI  - Kinetic characterization of the human retinoblastoma protein bipartite nuclear
      localization sequence (NLS) in vivo and in vitro. A comparison with the SV40
      large T-antigen NLS.
AB  - The retinoblastoma (RB) tumor suppressor is a nuclear phosphoprotein important
      for cell growth control and able to bind specifically to viral oncoproteins such
      as the SV40 large tumor antigen (T-ag). Human RB possesses a bipartite nuclear
      localization sequence (NLS) consisting of two clusters of basic amino acids
      within amino acids 860-877, also present in mouse and Xenopus homologs, which
      resembles that of nucleoplasmin. The T-ag NLS represents a different type of NLS,
      consisting of only one stretch of basic amino acids. To compare the nuclear
      import kinetics conferred by the bipartite NLS of RB to those conferred by the T
      ag NLS, we used beta-galactosidase fusion proteins containing the NLSs of either
      RB or T-ag. The RB NLS was able to target beta-galactosidase to the nucleus both
      in vivo (in microinjected cells of the HTC rat hepatoma line) and in vitro (in
      mechanically perforated HTC cells). Mutational substitution of the proximal basic
      residues of the NLS abolished nuclear targeting activity, confirming its
      bipartite character. Nuclear accumulation of the RB fusion protein was half
      maximal within about 8 min in vivo, maximal levels being between 3-4-fold those
      in the cytoplasm, which was less than 50% of the maximal levels attained by the T
      ag fusion protein, while the initial rate of nuclear import of the RB protein was
      also less than half that of T-ag. Nuclear import conferred by both NLSs in vitro
      was dependent on cytosol and ATP and inhibited by the nonhydrolyzable GTP analog
      GTPgammaS. Using an ELISA-based binding assay, we determined that the RB
      bipartite NLS had severely reduced affinity, compared with the T-ag NLS, for the
      high affinity heterodimeric NLS-binding protein complex importin 58/97, this
      difference presumably representing the basis of the reduced maximal nuclear
      accumulation and import rate in vivo. The results support the hypothesis that the
      affinity of NLS recognition by NLS-binding proteins is critical in determining
      the kinetics of nuclear protein import.

PMID- 9268358
TI  - The Saccharomyces cerevisiae peroxisomal 2,4-dienoyl-CoA reductase is encoded by
      the oleate-inducible gene SPS19.
AB  - beta-Oxidation is compartmentalized in mammals into both mitochondria and
      peroxisomes. Fatty acids with double bonds at even-numbered positions require for
      their degradation the auxiliary enzyme 2,4-dienoyl-CoA reductase, and at least
      three isoforms, two mitochondrial and one peroxisomal, exist in the rat. The
      Saccharomyces cerevisiae Sps19p is 34% similar to the human and rat mitochondrial
      reductases, and an SPS19 deleted strain was unable to utilize petroselineate (cis
      C18:1(6)) as the sole carbon source, but remained viable on oleate (cis
      C18:1(9)). Sps19p was purified to homogeneity from oleate-induced cells and the
      homodimeric enzyme (native molecular weight 69,000) converted 2,4-hexadienoyl-CoA
      into 3-hexenoyl-CoA in an NADPH-dependent manner and therefore contained 2,4
      dienoyl-CoA reductase activity. Antibodies raised against Sps19p decorated the
      peroxisomal matrix of oleate-induced cells. SPS19 shares with the sporulation
      specific SPS18 a common promoter region that contains an oleate response element.
      This element unidirectionally regulates transcription of the reductase and is
      sufficient for oleate induction of a promoterless CYC1-lacZ reporter gene. SPS19
      is dispensable for growth and sporulation on solid acetate and oleate media, but
      is essential for these processes to occur on petroselineate.

PMID- 9268359
TI  - The catalytic domain of protein kinase C chimeras modulates the affinity and
      targeting of phorbol ester-induced translocation.
AB  - Emerging evidence suggests important differences among protein kinase C (PKC)
      isozymes in terms of their regulation and biological functions. PKC is regulated
      by multiple interdependent mechanisms, including enzymatic activation,
      translocation of the enzyme in response to activation, phosphorylation, and
      proteolysis. As part of our ongoing studies to define the factors contributing to
      the specificity of PKC isozymes, we prepared chimeras between the catalytic and
      regulatory domains of PKCalpha, -delta, and -epsilon. These chimeras, which
      preserve the overall structure of the native PKC enzymes, were stably expressed
      in NIH 3T3 fibroblasts. Their intracellular distribution was similar to that of
      the endogenous enzymes, and they responded with translocation upon treatment with
      phorbol 12-myristate 13-acetate (PMA). We found that the potency of PMA for
      translocation of the PKCalpha/x chimeras from the soluble fraction was influenced
      by the catalytic domain. The ED50 for translocation of PKCalpha/alpha was 26 nM,
      in marked contrast to the ED50 of 0.9 nM in the case of the PKCalpha/epsilon
      chimera. In addition to this increase in potency, the site of translocation was
      also changed; the PKCalpha/epsilon chimera translocated mainly into the
      cytoskeletal fraction. PKCx/epsilon chimeras displayed twin isoforms with
      different mobilities on Western blots. PMA treatment increased the proportion of
      the higher mobility isoform. The two PKCx/epsilon isoforms differed in their
      localization; moreover, their localization pattern depended on the regulatory
      domain. Our results emphasize the complex contributions of the regulatory and
      catalytic domains to the overall behavior of PKC.

PMID- 9268360
TI  - Synergism between multiple virus-induced factor-binding elements involved in the
      differential expression of interferon A genes.
AB  - Comparative transfection analysis of murine interferon A4 and interferon A11
      promoter constructs transiently transfected in mouse L929 and human HeLa S3 cells
      infected with Newcastle disease virus showed that the second positive regulatory
      domain I-like domain (D motif), located between nucleotides -57 and -46 upstream
      of the transcription start site, contributes to the activation of virus-induced
      transcription of the interferon (IFN)-A4 gene promoter by cooperating with the
      positive regulatory domain I-like and TG-like domains previously described.
      Electrophoretic mobility shift assay performed with the virus-inducible fragments
      containing these motifs indicated that the binding activity that we have denoted
      as virus-induced factor (Genin, P., Braganca, J., Darracq, N., Doly, J., and
      Civas, A. (1995) Nucleic Acids Res. 23, 5055-5063) is different from interferon
      stimulated gene factor 3. It binds to the D motif but not to the virus
      unresponsive form of the D motif disrupted by a G-57 --> C substitution. We show
      that the low levels of IFN-A11 gene expression are caused essentially by the lack
      of two inducible enhancer domains disrupted by the A-78 --> G and the G-57 --> C
      substitutions. These data suggest a model taking account of the differential
      regulation of IFN-A gene family members. They also suggest that virus-induced
      factor may correspond to the primary transcription factor directly activated by
      virus that is involved in the initiation of IFN-A gene transcription.

PMID- 9268361
TI  - Relationship between yeast polyribosomes and Upf proteins required for nonsense
      mRNA decay.
AB  - In yeast, the accelerated rate of decay of nonsense mutant mRNAs, called nonsense
      mediated mRNA decay, requires three proteins, Upf1p, Upf2p, and Upf3p. Single,
      double, and triple disruptions of the UPF genes had nearly identical effects on
      nonsense mRNA accumulation, suggesting that the encoded proteins function in a
      common pathway. We examined the distribution of epitope-tagged versions of Upf
      proteins by sucrose density gradient fractionation of soluble lysates and found
      that all three proteins co-distributed with 80 S ribosomal particles and
      polyribosomes. Treatment of lysates with RNase A caused a coincident collapse of
      polyribosomes and each Upf protein into fractions containing 80 S ribosomal
      particles, as expected for proteins that are associated with polyribosomes.
      Mutations in the cysteine-rich (zinc finger) and RNA helicase domains of Upf1p
      caused loss of function, but the mutant proteins remained polyribosome
      associated. Density gradient profiles for Upf1p were unchanged in the absence of
      Upf3p, and although similar, were modestly shifted to fractions lighter than
      those containing polyribosomes in the absence of Upf2p. Upf2p shifted toward
      heavier polyribosome fractions in the absence of Upf1p and into fractions
      containing 80 S particles and lighter fractions in the absence of Upf3p. Our
      results suggest that the association of Upf2p with polyribosomes typically found
      in a wild-type strain depends on the presence and opposing effects of Upf1p and
      Upf3p.

PMID- 9268362
TI  - Fas- or ceramide-induced apoptosis is mediated by a Rac1-regulated activation of
      Jun N-terminal kinase/p38 kinases and GADD153.
AB  - In the present study, we show that Fas receptor ligation or cellular treatment
      with synthetic C6-ceramide results in activation or phosphorylation,
      respectively, of the small G-protein Rac1, Jun N-terminal kinase (JNK)/p38
      kinases (p38-K), and the transcription factor GADD153. A signaling cascade from
      the Fas receptor via ceramide, Ras, Rac1, and JNK/p38-K to GADD153 is
      demonstrated employing transfection of transdominant inhibitory N17Ras, N17Rac1,
      c-Jun, or treatment with a specific p38-K inhibitor. The critical function of
      this signaling cascade is indicated by prevention of Fas- or C6-ceramide-induced
      apoptosis after inhibition of Ras, Rac1, or JNK/p38-K.

PMID- 9268363
TI  - Calcium-dependent binding of sorcin to the N-terminal domain of synexin (annexin
      VII).
AB  - The annexins are characterized by their ability to bind phospholipid membranes in
      a Ca2+-dependent manner. Sequence variability between the N-terminal domains of
      the family members may contribute to the specific cellular function of each
      annexin. To identify proteins that interact with the N-terminal domain of synexin
      (annexin VII), a fusion protein was constructed composed of glutathione S
      transferase fused to amino acids 1-145 of human synexin. Affinity chromatography
      using this construct identified sorcin as a Ca2+-dependent synexin-binding
      protein. Overlay assays confirmed the interaction. The glutathione S-transferase
      construct associates with recombinant sorcin over the range of pCa2+ = 4.7-3.1
      with no binding observed at pCa2+ = 5.4. Overlay assays using deletion constructs
      of the synexin N-terminal domain mapped the sorcin binding site to the N-terminal
      31 amino acids of the synexin protein. Additionally, synexin forms a complex with
      sorcin and recruits this protein to chromaffin granule membranes in a Ca2+
      dependent manner. Sorcin is able to inhibit synexin-mediated chromaffin granule
      aggregation in a manner saturable with increasing sorcin concentrations, but does
      not influence the Ca2+ sensitivity of synexin-mediated granule aggregation.
      Therefore, the interaction between sorcin and synexin may serve to regulate the
      functions of these proteins on membrane surfaces in a Ca2+-dependent manner.

PMID- 9268364
TI  - SV40 large tumor antigen nuclear import is regulated by the double-stranded DNA
      dependent protein kinase site (serine 120) flanking the nuclear localization
      sequence.
AB  - Nuclear localization sequence (NLS)-dependent nuclear import of SV40 large tumor
      antigen (T-Ag) fusion proteins is regulated by phosphorylation sites for casein
      kinase II (CKII) and the cyclin-dependent kinase Cdc2 amino-terminal to the NLS
      (amino acids 126-132). Between the T-Ag CKII and Cdc2 sites is a site (Ser120)
      for the double-stranded DNA-dependent protein kinase (dsDNA-PK), which we show
      here for the first time to play a role in regulating T-Ag nuclear import. We
      replaced Ser120 by aspartic acid or alanine using site-directed mutagenesis and
      assessed the effects on nuclear transport kinetics both in vivo (microinjected
      cells) and in vitro (mechanically perforated cells) in HTC rat hepatoma cells.
      Maximal nuclear accumulation of the Asp120 and Ala120 protein derivatives was
      approximately 40% and 70% reduced in vivo, respectively, compared with that of
      the wild type protein, and similarly reduced in vitro, although to a lesser
      extent. This implies that the dsDNA-PK site regulates the maximal level of
      nuclear accumulation, normally functioning to enhance T-Ag nuclear transport; the
      higher accumulation of the Asp120 protein compared with the Ala120 protein
      indicates that negative charge at the dsDNA-PK site is mechanistically important
      in regulating nuclear import. The Asp120 protein accumulated in the nucleus at a
      faster rate than the wild type protein, implying that phosphorylation at Ser120
      may also regulate the nuclear import rate. CKII phosphorylation of the Asp120
      protein in cytosol or by purified CKII was approximately 30% higher than that of
      the Ser120 and Ala120 proteins, while negative charge at the CKII site increased
      dsDNA-PK phosphorylation of Ser120 by approximately 80% compared with wild type,
      implying physical and functional interactions between the two phosphorylation
      sites. Quantitation of NLS recognition by the importin 58/97 subunits using an
      enzyme-linked immunosorbent assay indicated that while the Ala120 protein
      derivative had a binding affinity very similar to that of wild type, the Asp120
      derivative showed 40% higher affinity. In vitro CKII phosphorylation increased
      importin binding by about 30% in all cases. These results imply that negative
      charge at the dsDNA-PK site may enhance nuclear import through increasing both
      NLS recognition by importin subunits, and phosphorylation at the CKII site, which
      itself also facilitates NLS recognition by importin 58/97.

PMID- 9268365
TI  - Butyrate activates the WAF1/Cip1 gene promoter through Sp1 sites in a p53
      negative human colon cancer cell line.
AB  - Butyrate is a well known colonic luminal short chain fatty acid, which arrests
      cell growth and induces differentiation in various cell types. We examined the
      effect of butyrate on the expression of WAF1/Cip1, a potent inhibitor of cyclin
      dependent kinases, and its relation to growth arrest in a p53-mutated human colon
      cancer cell line WiDr. Five millimolar butyrate completely inhibited the growth
      of WiDr and caused G1-phase arrest. WAF1/Cip1 mRNA was rapidly induced within 3 h
      by treatment with 5.0 mM butyrate, and drastic WAF1/Cip1 protein induction was
      detected. Using several mutant WAF1/Cip1 promoter fragments, we found that the
      butyrate-responsive elements are two Sp1 sites at -82 and -69 relative to the
      transcription start site. We also found that a TATA element at -46 and two
      overlapping consensus Sp1 sites at -60 and -55 are essential for the basal
      promoter activity of WAF1/Cip1. These findings suggest that butyrate arrests the
      growth of WiDr by activating the WAF1/Cip1 promoter through specific Sp1 sites in
      a p53-independent fashion.

PMID- 9268366
TI  - Functional mapping of the cytoplasmic region of intercellular adhesion molecule-3
      reveals important roles for serine residues.
AB  - Intercellular adhesion molecule-3 (ICAM-3), a ligand for beta2 integrins, elicits
      a variety of activation responses in lymphocytes. We describe a functional
      mapping study that focuses on the 37-residue cytoplasmic region of ICAM-3.
      Carboxyl-terminal truncations delineated portions involved in T cell antigen
      receptor costimulation, homotypic aggregation, and cellular spreading. Truncation
      of the membrane distal 25 residues resulted in loss of T cell antigen receptor
      costimulation as determined by interleukin 2 secretion. Aggregation and cell
      spreading were sensitive to truncation of the membrane distal and proximal thirds
      of the cytoplasmic portion. Phosphoamino acid analysis revealed that ICAM-3 from
      activated cells contained phosphoserine and phosphopeptide mapping identified
      Ser489 as a site of phosphorylation in vivo. Mutation of Ser489 or Ser515 to
      alanine blocked interleukin 2 secretion, aggregation and cell spreading, while
      mutation of other serine residues affected only a subset of functions. Ser489 was
      a phosphorylation site in vitro for recombinant protein kinase Ctheta. Finally,
      treatment of Jurkat cells with chelerythrine chloride, a protein kinase C
      inhibitor, prevented ICAM-3-triggered spreading. This study delineates separable
      regions and amino acid residues within the cytoplasmic portion of ICAM-3 that are
      important for T cell function.

PMID- 9268367
TI  - Enhancement of guanine-nucleotide exchange activity of C3G for Rap1 by the
      expression of Crk, CrkL, and Grb2.
AB  - Crk is an adaptor protein that consists almost entirely of SH2 and SH3 domains.
      We have previously demonstrated, by using in vivo and in vitro systems, that C3G,
      which was identified as a Crk SH3 domain-binding guanine nucleotide exchange
      factor, specifically activates Rap1. C3G also binds to other adaptor proteins,
      including CrkL and Grb2. In the present study, we analyzed the effect of Crk,
      CrkL, and Grb2 on the C3G-Rap1 pathway. Expression of Crk, CrkL, and Grb2 with
      C3G in Cos1 cells significantly increased the ratio of GTP/GDP bound to Rap1.
      Both the SH2 and SH3 domains of Crk were required for this activity. However, Crk
      did not stimulate the guanine nucleotide exchange activity of C3G for Rap1 in
      vitro, suggesting that Crk does not activate C3G by an allosteric mechanism. The
      requirement of the SH2 domain of Crk for the enhancement of guanine nucleotide
      exchange activity for Rap1 could be compensated for by the addition of a
      farnesylation signal to Crk, indicating that Crk enhanced the guanine nucleotide
      exchange activity of C3G by membrane recruitment of C3G. These results
      demonstrate that Crk, CrkL, and Grb2 positively modulate the C3G-Rap1 pathway
      primarily by recruiting C3G to the cell membrane.

PMID- 9268368
TI  - Role of protein-phospholipid interactions in the activation of ARF1 by the
      guanine nucleotide exchange factor Arno.
AB  - Arno is a 47-kDa human protein recently identified as a guanine nucleotide
      exchange factor for ADP ribosylation factor 1 (ARF1) with a central Sec7 domain
      responsible for the exchange activity and a carboxyl-terminal pleckstrin homology
      (PH) domain (Chardin, P., Paris, S., Antonny, B., Robineau, S., Beraud-Dufour,
      S., Jackson, C. L., and Chabre, M. (1996) Nature 384, 481-484). Binding of the PH
      domain to phosphatidylinositol 4,5-bisphosphate (PIP2) greatly enhances Arno
      mediated activation of myristoylated ARF1. We show here that in the absence of
      phospholipids, Arno promotes nucleotide exchange on [Delta17]ARF1, a soluble
      mutant of ARF1 lacking the first 17 amino acids. This reaction is unaffected by
      PIP2, which suggests that the PIP2-PH domain interaction does not directly
      regulate the catalytic activity of Arno but rather serves to recruit Arno to
      membranes. Arno catalyzes the release of GDP more efficiently than that of GTP
      from [Delta17]ARF1, and a stable complex between Arno Sec7 domain and nucleotide
      free [Delta17]ARF1 can be isolated. In contrast to [Delta17]ARF1, full-length
      unmyristoylated ARF1 is not readily activated by Arno in solution. Its activation
      requires the presence of phospholipids and a reduction of ionic strength and Mg2+
      concentration. PIP2 is strongly stimulatory, indicating that binding of Arno to
      phospholipids is involved, but in addition, electrostatic interactions between
      phospholipids and the amino-terminal portion of unmyristoylated ARF1GDP seem to
      be important. We conclude that efficient activation of full-length ARF1 by Arno
      requires a membrane surface and two distinct protein-phospholipid interactions:
      one between the PH domain of Arno and PIP2, and the other between amino-terminal
      cationic residues of ARF1 and anionic phospholipids. The latter interaction is
      normally induced by insertion of the amino-terminal myristate into the bilayer
      but can also be artificially facilitated by decreasing Mg2+ and salt
      concentrations.

PMID- 9268369
TI  - Sex-lethal interactions with protein and RNA. Roles of glycine-rich and RNA
      binding domains.
AB  - Sex-lethal (Sxl) is an RNA-binding protein, containing two conserved RNA binding
      domains (RBDs) and a glycine-rich region, which functions as a regulator of
      alternative splicing in Drosophila sex determination. Previous work demonstrated
      that Sxl monomers interact cooperatively upon binding to target RNAs and that the
      cooperativity depends on the glycine-rich N terminus. Here we use band shift
      experiments to show that RNA binding patterns are altered when Sxl is combined
      with other proteins having similar glycine-rich domains, including mammalian
      heterogeneous nuclear (hn) RNP L and Drosophila Hrb87F (an hnRNP A/B homolog).
      Direct involvement of the Sxl glycine-rich region in protein interactions was
      verified by Far-Western analysis. Two interaction domains, the Sxl N terminus and
      the Sxl first RNA binding domain, were suggested by the yeast two-hybrid assay.
      In a systematic examination of the RNA binding properties of Sxl domains, it was
      found that the Sxl termini as well as the RBDs influence RNA binding specificity.
      Finally, selection of the Sxl optimal binding site (SELEX) confirms the
      importance of U-runs in the Sxl binding site and suggests a second type of non-U
      run target that may be associated with RNA secondary structure.

PMID- 9268370
TI  - A bipartite model of 2-5A-dependent RNase L.
AB  - The 2-5A-dependent RNase (RNase L) is a tightly regulated endoribonuclease of
      higher vertebrates that is catalytically active only after engaging unusual
      effector molecules consisting of the 2',5'-linked oligoadenylates, p1
      3A(2'p5'A)>/=2 (2-5A). Progressive truncations from either terminus have provided
      insight into the structure, function, and regulation of RNase L. We determined
      that deletion of the N-terminal 335 amino acids of RNase L, about 45% of the
      enzyme, produced a constitutively active endoribonuclease, thus effectively
      eliminating the requirement for 2-5A. The truncated nuclease had 6-fold lower
      catalytic activity against an oligo(rU) substrate than wild type RNase L.
      However, the two enzymes showed identical RNA cleavage site preferences with an
      mRNA as substrate. The repressor function required only the last three of a
      series of nine ankyrin-like repeats present in the N-terminal part of RNase L. In
      contrast, the entire ankyrin repeat region was necessary and sufficient for 2-5A
      binding activity. Deletion of a 10-amino acid sequence near the C terminus of
      RNase L, between residues 710 and 720, eliminated both the catalytic and RNA
      substrate binding functions of the enzyme. The ability to bind native RNase L in
      response to 2-5A required amino acid sequences near both termini of the protein.
      A bipartite model for the structure of RNase L emerged in which the regulatory
      functions of the molecule are located in the N-terminal half, while the catalytic
      domain is present in the C-terminal half.

PMID- 9268371
TI  - Specific interactions of the autoantigen L7 with multi-zinc finger protein ZNF7
      and ribosomal protein S7.
AB  - The eucaryotic protein L7, which associates with the large subunit of ribosomes,
      has been shown to be a major autoantigen in systemic autoimmune arthritis. The N
      terminus carries a sequence motif that is similar to the leucine zipper domain of
      eucaryotic transcription factors. This domain promotes the homodimerization of
      protein L7 through alpha-helical coiled-coil formation and binds to distinct
      mRNAs, thereby inhibiting their cell-free translation. Using a yeast two-hybrid
      selection, we have identified from a Jurkat T lymphoma cDNA library ribosomal
      protein S7 and the multi-zinc finger protein ZNF7 as proteins that interact with
      protein L7. A fragment of L7 carrying the leucine zipper-like domain is fully
      sufficient to mediate these interactions. Their potential biological significance
      is indicated by low apparent dissociation constants of S7-L7 (15 x 10(-9) M) and,
      respectively, ZNF7-L7 (2 x 10(-9) M) complexes and co-immunoprecipitation of
      proteins S7, ZNF7, and L7 from a cell lysate with an anti-L7 antibody. We also
      show that ZNF7-like L7 and S7 can exist in a ribosome-bound form. This study
      provides further evidence suggesting that L7 is involved in translational
      regulation through interactions with components of the translational apparatus.

PMID- 9268372
TI  - Glycerol-assisted restorative adjustment of flavoenzyme conformation perturbed by
      site-directed mutagenesis.
AB  - The replacement of histidine 307 with leucine in pig kidney D-amino acid oxidase
      perturbs its active site conformation accompanied by dramatic losses in protein
      flavin interactions and enzymatic activity. However, the negative effect of this
      mutation on the holoenzyme structure is essentially eliminated in the presence of
      glycerol, resulting in up to 50% activity recovery and greater than 16-fold
      increase in the flavin affinity. Further analysis revealed that glycerol assists
      in the rearrangement of the protein toward its holoenzyme-like conformation
      together with reduction in the solvent-accessible protein hydrophobic area as
      demonstrated by limited proteolysis and use of affinity and hydrophobic probes. A
      substantial decrease in the protein-flavin interactions was demonstrated at a low
      temperature, but this reversible process was completely blocked in the presence
      of 40% glycerol. We suggest that the perturbation of the D-amino acid oxidase
      active site is due to the nonpolar nature of the mutation whose negative impact
      on the holoenzyme structure can be overcome by glycerol-induced strengthening of
      protein internal hydrophobic interactions.

PMID- 9268373
TI  - Protein-protein interaction specificity of Im9 for the endonuclease toxin colicin
      E9 defined by homologue-scanning mutagenesis.
AB  - The colicin DNase-specific immunity proteins interact with the endonuclease
      domain of the bacterial toxin colicin E9 with dissociation constants that span
      the millimolar to femtomolar affinity range. Among the non-cognate interactions
      Im2 shows the strongest binding toward the E9 DNase domain with a Kd of 10(-8) M,
      6 orders of magnitude weaker than that of the cognate immunity protein Im9. Based
      on a NMR structure of Im9 that shows it to be a 4-helix protein, we have
      conducted a mutagenic scan in which elements of Im9 secondary structure were
      substituted into Im2 to precisely delineate regions that define specificity.
      Eleven chimeras were constructed, and their biological cross-reactivity toward
      colicins E2 and E9 was evaluated. From this set of mutants seven proteins were
      purified, and the Kd for their interaction with the E9 DNase domain was measured
      by a combination of stopped-flow fluorescence and subunit exchange kinetics. Our
      results show that immunity specificity is dominated by residues on helix II,
      accounting for 5 orders of magnitude binding specificity relative to Im2, and
      that packing interactions of helix II with its neighbor helix I and the loop
      connecting helix III with helix IV play minor roles. The conformational stability
      of these chimeric proteins was also determined. Proteins displaying an Im9
      phenotype were all more stable than the parent Im2 protein, and surprisingly some
      chimeras were significantly more stable than either Im2 or Im9.

PMID- 9268374
TI  - Down-regulation of the cyclin A promoter by transforming growth factor-beta1 is
      associated with a reduction in phosphorylated activating transcription factor-1
      and cyclic AMP-responsive element-binding protein.
AB  - Transforming growth factor (TGF)-beta1 prevents cell cycle progression by
      inhibiting several regulators, including cyclin A. To study the mechanisms by
      which TGF-beta1 down-regulates cyclin A gene expression, we transfected reporter
      plasmids driven by the cyclin A promoter into mink lung epithelial cells in the
      absence and presence of TGF-beta1. The TGF-beta1-induced down-regulation of
      cyclin A promoter activity appeared to be mediated via the activating
      transcription factor (ATF) site, because mutation of this site abolished down
      regulation. Surprisingly, although TGF-beta1 treatment for 24 h markedly
      decreased cyclin A promoter activity, it did not decrease the abundance of the
      ATF-binding proteins ATF-1 and cyclic AMP-responsive binding protein (CREB).
      However, we detected 90 and 78% reductions (by Western analysis) in
      phosphorylated CREB and ATF-1, respectively, in mink lung epithelial cells
      treated with TGF-beta1. TGF-beta1-induced down-regulation of cyclin A promoter
      activity was reversed by okadaic acid (a phosphatase inhibitor) and by
      cotransfection with plasmids expressing the cAMP-dependent protein kinase
      catalytic subunit or the simian virus small tumor antigen (Sm-t, an inhibitor of
      PP2A). These data indicate that TGF-beta1 may down-regulate cyclin A promoter
      activity by decreasing phosphorylation of CREB and ATF-1.

PMID- 9268375
TI  - Interaction of Gsalpha with the cytosolic domains of mammalian adenylyl cyclase.
AB  - Forskolin- and Gsalpha-stimulated adenylyl cyclase activity is observed after
      mixture of two independently-synthesized approximately 25-kDa cytosolic fragments
      derived from mammalian adenylyl cyclases (native Mr approximately 120,000). The
      C1a domain from type V adenylyl cyclase (VC1) and the C2 domain from type II
      adenylyl cyclase (IIC2) can both be expressed in large quantities and purified to
      homogeneity. When mixed, their maximally stimulated specific activity, 150
      micromol/min/mg protein, substantially exceeds values observed previously with
      the intact enzyme. A soluble, high-affinity complex containing one molecule each
      of VC1, IIC2, and guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS)-Gsalpha is
      responsible for the observed enzymatic activity and can be isolated. In addition,
      GTPgammaS-Gsalpha interacts with homodimers of IIC2 to form a heterodimeric
      complex (one molecule each of Gsalpha and IIC2) but not detectably with
      homodimers of VC1. Nevertheless, Gsalpha can be cross-linked to VC1 in the
      activated heterotrimeric complex of VC1, IIC2, and Gsalpha, indicating its
      proximity to both components of the enzyme that are required for efficient
      catalysis. These results and those in the accompanying report (Dessauer, C. W.,
      Scully, T. T., and Gilman, A. G. (1997) J. Biol. Chem. 272, 22272-22277) suggest
      that activators of adenylyl cyclase facilitate formation of a single, high
      activity catalytic site at the interface between C1 and C2.

PMID- 9268376
TI  - Interactions of forskolin and ATP with the cytosolic domains of mammalian
      adenylyl cyclase.
AB  - Fragments of the two cytoplasmic domains of mammalian adenylyl cyclases can be
      synthesized independently (and abundantly) as soluble proteins; Gsalpha- and
      forskolin-stimulated enzymatic activity is restored upon their mixture. We have
      utilized this system to characterize the interactions of adenylyl cyclase with
      forskolin and its substrate, ATP. In the presence of Gsalpha, adenylyl cyclase is
      activated in response to occupation of only one forskolin-binding site. A single
      binding site for forskolin was identified by equilibrium dialysis; its Kd (0.1
      microM) corresponds to the EC50 for enzyme activation. The affinity of forskolin
      for adenylyl cyclase is greatly reduced in the absence of Gsalpha ( approximately
      40 microM). Binding of forskolin to the individual cytoplasmic domains of the
      enzyme was not detected. A single binding site for the ATP analog, alpha,beta
      methylene ATP (Ap(CH2)pp), was also detected by equilibrium dialysis. Such
      binding was not observed with the individual domains. Binding of Ap(CH2)pp was
      unaffected by P-site inhibitors of adenylyl cyclase. A modified P-loop sequence
      located near the carboxyl terminus of adenylyl cyclase has been implicated in ATP
      binding. Mutation of the conserved, non-glycine residues within this region
      caused no significant changes in the Km for ATP or the Ki for Ap(CH2)pp. It thus
      seems unlikely that this region is part of the active site. However, a mutation
      in the C1 domain (E518A) causes a 10-fold decrease in the binding affinity for
      Ap(CH2)pp. This residue and the active site of the enzyme may lie at the
      interface between the two cytosolic domains.

PMID- 9268377
TI  - Distinct domains of the RelA NF-kappaB subunit are required for negative cross
      talk and direct interaction with the glucocorticoid receptor.
AB  - The RelA subunit of NF-kappaB and the glucocorticoid receptor mutually repress
      each others transcriptional activity, thus providing a mechanism for
      immunosuppression. Deletion analysis of the glucocorticoid receptor has shown
      that the DNA binding domain and the ligand binding domain are essential
      components for repression. Here, we show by deletions and point mutations that
      both the Rel homology domain and the transactivation domains of RelA are required
      for repression of the transcriptional activity of the glucocorticoid receptor in
      intact cells. However, only the Rel homology domain of RelA was found to
      associate with the glucocorticoid receptor in vitro. RelA mutants, not able to
      repress glucocorticoid receptor activity, but still able to dimerize, behaved as
      transdominant inhibitors of the repressive activity of wild type RelA.
      Furthermore, we show that the 13 S E1A protein is able to interfere with the
      transrepressive activity of RelA. We propose that negative cross-talk between the
      glucocorticoid receptor and RelA is due to direct interaction via the Rel
      homology domain of RelA and the DNA binding domain of the glucocorticoid receptor
      in combination with interference by the transactivation domains of RelA with the
      transcriptional activity of the glucocorticoid receptor.

PMID- 9268378
TI  - Anchor structure of staphylococcal surface proteins. A branched peptide that
      links the carboxyl terminus of proteins to the cell wall.
AB  - Surface proteins of Staphylococcus aureus are anchored to the cell wall by a
      mechanism requiring a COOH-terminal sorting signal. Previous work demonstrated
      that the sorting signal is cleaved at the conserved LPXTG motif and that the
      carboxyl of threonine (T) is linked to the staphylococcal cell wall. By employing
      different cell wall lytic enzymes, surface proteins were released from the
      staphylococcal peptidoglycan and their COOH-terminal anchor structure was
      revealed by a combination of mass spectrometry and chemical analysis. The results
      demonstrate that surface proteins are linked to a branched peptide (NH2-Ala-gamma
      Gln-Lys-(NH2-Gly5)-Ala-COOH) by an amide bond between the carboxyl of threonine
      and the amino of the pentaglycine cross-bridge that is attached to the epsilon
      amino of lysyl. This branched anchor peptide is amide-linked to the carboxyl of N
      acetylmuramic acid, thereby tethering the COOH-terminal end of surface proteins
      to the staphylococcal peptidoglycan.

PMID- 9268379
TI  - Differential utilization of ShcA tyrosine residues and functional domains in the
      transduction of epidermal growth factor-induced mitogen-activated protein kinase
      activation in 293T cells and nerve growth factor-induced neurite outgrowth in
      PC12 cells. Identification of a new Grb2.Sos1 binding site.
AB  - By transient expression of both truncated forms of p52(SHCA) and those with point
      mutations in 293T cells, it has been shown that, in addition to Tyr-317, Tyr
      239/240 is a major site of phosphorylation that serves as a docking site for
      Grb2.Sos1 complexes. In addition, analysis of epidermal growth factor (EGF)
      induced activation of mitogen-activated protein kinase in 293T cells showed that
      the overexpression Shc SH2 or phosphotyrosine binding (PTB) domains of ShcA alone
      has a more potent negative effect than the overexpression of the forms of ShcA
      lacking Tyr-317 or Tyr 239/240 or both. In transiently transfected PC12 cells,
      the ShcA PTB domain and tyrosine phosphorylation in the CH1 domain, especially on
      Tyr-239/240, are crucial for mediating nerve growth factor (NGF)-induced neurite
      outgrowth. These findings suggest that the EGF and NGF (TrkA) receptor can
      utilize Shc in different ways to promote their activity. For EGF-induced mitogen
      activated protein kinase activation in 293T cells, both Shc PTB and SH2 domains
      are essential for optimal activation, indicating that a mechanism independent of
      Grb2 engagement with Shc may exist. For NGF-induced neurite outgrowth in PC12
      cells, Shc PTB plays an essential role, and phosphorylation on Tyr-239/240, but
      not on Tyr-317, is required.

PMID- 9268380
TI  - Human Myt1 is a cell cycle-regulated kinase that inhibits Cdc2 but not Cdk2
      activity.
AB  - Activation of the Cdc2.cyclin B kinase is a pivotal step of mitotic initiation.
      This step is mediated principally by the dephosphorylation of residues threonine
      14 (Thr14) and tyrosine 15 (Tyr15) on the Cdc2 catalytic subunit. In several
      organisms homologs of the Wee1 kinase have been shown to be the major activity
      responsible for phosphorylating the Tyr15 inhibitory site. A membrane-bound
      kinase capable of phosphorylating residue Thr14, the Myt1 kinase, has been
      identified in the frog Xenopus laevis and more recently in human. In this study,
      we have examined the substrate specificity and cell cycle regulation of the human
      Myt1 kinase. We find that human Myt1 phosphorylates and inactivates Cdc2
      containing cyclin complexes but not complexes containing Cdk2 or Cdk4. Analysis
      of endogenous Myt1 demonstrates that it remains membrane-bound throughout the
      cell cycle, but its kinase activity decreased during M phase arrest, when Myt1
      became hyperphosphorylated. Further, Cdc2. cyclin B1 was capable of
      phosphorylating Myt1 in vitro, but this phosphorylation did not affect Myt1
      kinase activity. These findings suggest that human Myt1 is negatively regulated
      by an M phase-activated kinase and that Myt1 inhibits mitosis due to its
      specificity for Cdc2.cyclin complexes.

PMID- 9268381
TI  - Activation-induced aggregation and processing of the human Fas antigen. Detection
      with cytoplasmic domain-specific antibodies.
AB  - Fas (APO1/CD95) is a type 1 transmembrane protein critically involved in receptor
      mediated apoptosis. Previous studies have shown that Fas exists in monomeric form
      in resting cells and aggregates upon cross-linking to form a complex that serves
      to recruit additional signaling molecules to the cell membrane. To study the
      molecular fate of the Fas antigen following receptor activation, a monoclonal
      antibody specific for the cell death domain of Fas has been generated. This
      monoclonal antibody (3D5) could be used in Western blot analysis using total cell
      lysates to identify different forms of Fas antigens without immunoprecipitation.
      High molecular mass (>200 kDa), SDS- and beta-mercaptoethanol-resistant Fas
      aggregates were formed immediately following receptor cross-linking, and a 97-kDa
      band (p97) was detected about 2 h later. p97 could be detected by antibodies
      against either the death domain or the C terminus. However, p97 could not be
      precipitated by antiextracellular domain antibodies. Thus, p97 most likely
      represents a processed form of the high molecular weight Fas aggregates. Although
      p97 generation followed a similar time course as CPP32 activation and poly(ADP
      ribose) polymerase cleavage, it could not be inhibited by cysteine protease,
      calpain, or proteasome inhibitors.

PMID- 9268382
TI  - Tissue-specific heterogeneity in alpha-dystroglycan sialoglycosylation. Skeletal
      muscle alpha-dystroglycan is a latent receptor for Vicia villosa agglutinin b4
      masked by sialic acid modification.
AB  - Because the polypeptide core of alpha-dystroglycan is encoded by a single gene,
      the difference in apparent molecular mass between alpha-dystroglycans expressed
      in various tissues is presumably due to differential glycosylation. However,
      little is presently known about the tissue-specific differences in alpha
      dystroglycan glycosylation and whether these modifications may confer functional
      variability to alpha-dystroglycan. We recently observed that laminin-1 binding to
      skeletal muscle alpha-dystroglycan was dramatically inhibited by heparin, whereas
      the binding of commercial merosin to skeletal muscle alpha-dystroglycan was only
      marginally inhibited (Pall, E. A., Bolton, K. M., and Ervasti, J. M. (1996) J.
      Biol. Chem. 3817-3821). In contrast to 156-kDa skeletal muscle alpha
      dystroglycan, both laminin-1 and merosin binding to 120-kDa brain alpha
      dystroglycan were sensitive to heparin. We have now examined the laminin binding
      properties of 140-kDa alpha-dystroglycan purified from cardiac muscle and
      observed that like skeletal muscle alpha-dystroglycan, heparin inhibited cardiac
      alpha-dystroglycan binding to laminin-1, but not to merosin. On the other hand,
      cardiac and brain alpha-dystroglycans could be distinguished from skeletal muscle
      alpha-dystroglycan by their reactivity with the terminal GalNAc-specific lectin
      Vicia villosa agglutinin. Interestingly, skeletal muscle alpha-dystroglycan
      became reactive with V. villosa agglutinin upon digestion with sialidase from
      Clostridium perfringens, Arthrobacter neurofaciens, or Streptococcus, but not
      Vibrio cholerae or Newcastle disease virus sialidase. While none of the sialidase
      treatments affected the laminin binding properties of alpha-dystroglycan, the sum
      of our results suggests that skeletal muscle alpha-dystroglycan contains a novel
      sialic acid residue linked alpha2-6 to GalNAc. These properties are also
      consistent with the cellular characteristics of a GalNAc-terminated
      glycoconjugate recently implicated in neuromuscular synaptogenesis. Thus,
      variations in alpha-dystroglycan sialoglycosylation may prove as useful markers
      to further elucidate the role of alpha-dystroglycan glycoforms in different
      tissues and perhaps within a single cell type.

PMID- 9268383
TI  - Mapping patterns of CpG island methylation in normal and neoplastic cells
      implicates both upstream and downstream regions in de novo methylation.
AB  - Promoter region CpG island methylation is associated with tumor suppressor gene
      silencing in neoplasia. GenBank sequence analyses revealed that a number of CpG
      islands are juxtaposed to multiple Alu repeats, which have been proposed as "de
      novo methylation centers." These islands also contain multiple Sp1 elements
      located upstream and downstream of transcription start, which have been shown to
      protect CpG islands from methylation. We mapped the methylation patterns of the E
      cadherin (E-cad) and von Hippel-Lindau (VHL) tumor suppressor gene CpG island
      regions in normal and neoplastic cells. Although unmethylated in normal tissue,
      these islands were embedded between densely methylated flanking regions
      containing multiple Alu repeats. These methylated flanks were segregated from the
      unmethylated, island CpG sites by Sp1-rich boundary regions. Finally, in human
      fibroblasts overexpressing DNA methyltransferase, de novo methylation of the E
      cad CpG island initially involved sequences at both ends of the island and the
      adjacent, flanking regions and progressed with time to encompass the entire CpG
      island region. Together, these data suggest that boundaries exist at both ends of
      a CpG island to maintain the unmethylated state in normal tissue and that these
      boundaries may be progressively overridden, eliciting the de novo methylation
      associated with tumor suppressor gene silencing in neoplasia.

PMID- 9268384
TI  - A selective inverse agonist for central cannabinoid receptor inhibits mitogen
      activated protein kinase activation stimulated by insulin or insulin-like growth
      factor 1. Evidence for a new model of receptor/ligand interactions.
AB  - In the present study, we showed that Chinese hamster ovary (CHO) cells
      transfected with human central cannabinoid receptor (CB1) exhibit high
      constitutive activity at both levels of mitogen-activated protein kinase (MAPK)
      and adenylyl cyclase. These activities could be blocked by the CB1-selective
      ligand, SR 141716A, that functions as an inverse agonist. Moreover, binding
      studies showed that guanine nucleotides decreased the binding of the agonist CP
      55,940, an effect usually observed with agonists, whereas it enhanced the binding
      of SR 141716A, a property of inverse agonists. Unexpectedly, we found that CB1
      mediated effects of SR 141716A included inhibition of MAPK activation by
      pertussis toxin-sensitive receptor-tyrosine kinase such as insulin or insulin
      like growth factor 1 receptors but not by pertussis toxin-insensitive receptor
      tyrosine kinase such as the fibroblast growth factor receptor. We also observed
      similar results when cells were stimulated with Mas-7, a mastoparan analog, that
      directly activates the Gi protein. Furthermore, SR 141716A inhibited guanosine 5'
      0-(thiotriphosphate) uptake induced by CP-55,940 or Mas-7 in CHO-CB1 cell
      membranes. This indicates that, in addition to the inhibition of autoactivated
      CB1, SR 141716A can deliver a biological signal that blocks the Gi protein and
      consequently abrogates most of the Gi-mediated responses. By contrast, SR 141716A
      had no effect on MAPK activation by insulin or IGF1 in CHO cells lacking CB1
      receptors, ruling out the possibility of a direct interaction of SR 141716A with
      the Gi protein. This supports the notion that the Gi protein may act as a
      negative intracellular signaling cross-talk molecule. From these original
      results, which considerably enlarge the biological properties of the inverse
      agonist, we propose a novel model for receptor/ligand interactions.

PMID- 9268385
TI  - Acidic residues necessary for pyrophosphate-energized pumping and inhibition of
      the vacuolar H+-pyrophosphatase by N,N'-dicyclohexylcarbodiimide.
AB  - On the basis of a revised topological model of the vacuolar H+-pyrophosphatase (V
      PPase; EC 3.6.1.1) derived from the analysis of four published sequences using
      two structure-predicting programs, TopPred II and MEMSAT, eight acidic amino acid
      residues located near or within transmembrane alpha-helices were identified. The
      codons specifying these amino acids in the cDNA encoding the V-PPase from
      Arabidopsis thaliana were singly mutated to examine their involvement in
      pyrophosphate (PPi) hydrolysis and PPi-dependent H+ translocation and the
      functional significance of the similarities between the sequences encompassing
      Glu229 (227-245) of the V-PPase and the N,N'-dicyclohexylcarbodiimide (DCCD)
      binding transmembrane alpha-helix of the c-subunits of F-ATPases (Nyren, P.,
      Sakai-Nore, Y. , and Strid, A. (1993) Plant Cell Physiol. 34, 375-378). Three
      functional classes were identified after heterologous expression of mutated
      enzyme in Saccharomyces cerevisiae. Class I (E119Q, E229Q, D573N, E667Q, and
      E751Q) mutants exhibited PPi hydrolytic and H+ translocation activities and DCCD
      sensitivities similar to wild type. The one class II mutant obtained (E427Q) was
      preferentially impaired for H+ translocation over PPi hydrolysis but retained
      sensitivity to DCCD. Class III (E305Q and D504N) mutants exhibited a near
      complete abolition of both PPi hydrolysis and H+ translocation and residual
      activities with decreased DCCD sensitivity. In none of the mutants was diminished
      insertion of the V-PPase into the membrane or an increase in the background
      conductance of the membrane to H+ evident. The decoupled character of E427Q
      mutants and the enhancement of H+ pumping in E427D mutants by comparison with
      wild type, in conjunction with the retention of DCCD inhibitability in both E427Q
      and E427D mutants, implicate a role for Glu427 in DCCD-insensitive H+
      translocation by the V-PPase. The proportionate diminution of PPi hydrolytic and
      H+ translocation activity and conservation of wild type DCCD sensitivity in E229Q
      mutants refute the notion that Glu229 is the residue whose covalent modification
      by DCCD is responsible for the abolition of PPi-dependent H+ translocation.
      Instead, the diminished sensitivity of the residual activities of E305Q and D504N
      mutants, but not E305D or D504E mutants, to inhibition by DCCD is consistent with
      the involvement of acidic residues at these positions in inhibitory DCCD binding.
      The results are discussed with regard to the possible involvement of Glu427 in
      coupling PPi hydrolysis with transmembrane H+ translocation and earlier
      interpretations of the susceptibility of the V-PPase to inhibition by
      carbodiimides.

PMID- 9268386
TI  - Selective inhibition of growth factor-stimulated mitogenesis by a cell-permeable
      Grb2-binding peptide.
AB  - The activation of the mitogen-activated protein kinase (MAPK) cascade by a
      variety of growth factors and other agents is central to a mitogenic response. In
      the case of polypeptide growth factors such as the epidermal growth factor (EGF)
      and platelet-derived growth factor (PDGF), the steps leading to activation of
      MAPK require the function of the adaptor protein Grb2 (growth factor receptor
      binding protein 2), which can bind either directly or indirectly via its Src
      homology 2 domain to activated receptor tyrosine kinases. A cell-permeable
      mimetic of the EGF receptor Grb2 binding site has been investigated for its
      ability to inhibit biological responses stimulated by a variety of growth
      factors. Pretreatment of cells with this peptide results in the accumulation of
      the peptide in cells and its association with Grb2. This is associated with a
      complete inhibition of the mitogenic response stimulated by EGF and PDGF. In
      contrast, the peptide has no effect on the mitogenic response stimulated by
      fibroblast growth factor. The peptide could also inhibit the phosphorylation of
      MAPK stimulated with EGF and PDGF in the absence of an effect on the fibroblast
      growth factor response. These data demonstrate that cell-permeable mimetics of
      Src homology 2 binding sites can selectively inhibit growth factor-stimulated
      mitogenesis, and also directly demonstrate specificity in the coupling of
      activated receptor tyrosine kinases to the MAPK cascade.

PMID- 9268387
TI  - Structure and function of RNA polymerase II elongation factor ELL. Identification
      of two overlapping ELL functional domains that govern its interaction with
      polymerase and the ternary elongation complex.
AB  - The human ELL gene on chromosome 19p13.1 undergoes frequent translocations with
      the trithorax-like MLL gene on chromosome 11q23 in acute myeloid leukemia.
      Recently, the human ELL gene was shown to encode an RNA polymerase II elongation
      factor that activates elongation by suppressing transient pausing by polymerase
      at many sites along the DNA. In this report, we identify and characterize two
      overlapping ELL functional domains that govern its interaction with RNA
      polymerase II and the ternary elongation complex. Our findings reveal that, in
      addition to its elongation activation domain, ELL contains a novel type of RNA
      polymerase II interaction domain that is capable of negatively regulating
      polymerase activity in promoter-specific transcription initiation in vitro.
      Notably, the MLL-ELL translocation results in deletion of a portion of this
      functional domain, and ELL mutants lacking sequences deleted by the translocation
      bind RNA polymerase II and are fully active in elongation, but fail to inhibit
      initiation. Taken together, these results raise the possibility that the MLL-ELL
      translocation could alter ELL-RNA polymerase II interactions that are not
      involved in regulation of elongation.

PMID- 9268388
TI  - Amyloid beta-protein fibrillogenesis. Detection of a protofibrillar intermediate.
AB  - Fibrillogenesis of the amyloid beta-protein (Abeta) is a seminal pathogenetic
      event in Alzheimer's disease. Inhibiting fibrillogenesis is thus one approach
      toward disease therapy. Rational design of fibrillogenesis inhibitors requires
      elucidation of the stages and kinetics of Abeta fibrillogenesis. We report
      results of studies designed to examine the initial stages of Abeta
      oligomerization. Size exclusion chromatography, quasielastic light scattering
      spectroscopy, and electron microscopy were used to characterize fibrillogenesis
      intermediates. After dissolution in 0.1 M Tris-HCl, pH 7.4, and removal of pre
      existent seeds, Abeta chromatographed almost exclusively as a single peak. The
      molecules composing the peak had average hydrodynamic radii of 1.8 +/- 0.2 nm,
      consistent with the predicted size of dimeric Abeta. Over time, an additional
      peak, with a molecular weight >100,000, appeared. This peak contained
      predominantly curved fibrils, 6-8 nm in diameter and <200 nm in length, which we
      have termed "protofibrils." The kinetics of protofibril formation and
      disappearance are consistent with protofibrils being intermediates in the
      evolution of amyloid fibers. Protofibrils appeared during the polymerization of
      Abeta-(1-40), Abeta-(1-42), and Abeta-(1-40)-Gln22, peptides associated with both
      sporadic and inherited forms of Alzheimer's disease, suggesting that protofibril
      formation may be a general phenomenon in Abeta fibrillogenesis. If so,
      protofibrils could be attractive targets for fibrillogenesis inhibitors.

PMID- 9268411
TI  - The peer relations of dropouts: a comparative study of at-risk and not at-risk
      youths.
AB  - Little research has been devoted to exploring the relationship between high
      school disengagement and friendship network changes. In this study, the
      characteristics of friends, the environments of the friendship network and the
      nature of peer relations of students at-risk and not at-risk of dropping out of
      high school were compared. A questionnaire was given to 191 high school students
      (109 males, 82 females) from a middle class environment at the beginning and end
      of the school year. Results indicated that at-risk students had more dropout
      friends, more working friends, fewer school friends and fewer same-sex friends.
      Sex differences were discovered in several areas. Findings are discussed in
      relation to research and theories pertaining to dropouts and adolescent
      development.

PMID- 9268412
TI  - An examination of adolescent risk-taking using a story completion task.
AB  - The aim of the study was to assess whether risk-taking as described in complete
      the story tasks written by adolescents could be predicted by the perceived
      consequences of the behaviours portrayed in the stories. The study involved
      analysis of story themes in terms of portrayal of participation in risky
      behaviour and the nature of story outcomes. Links between story elements were
      assessed and comparisons made of these projectively-based findings with previous
      self-report research. Participants were 570 adolescents aged 12 to 17 from
      secondary schools in Melbourne, Australia. Responses to four complete the story
      stimuli were coded according to whether story protagonists participated in the
      hypothetical risk posed, and in terms of the behavioural outcomes presented.
      Adolescents were more likely to write stores accepting negative than positive
      risks, and to expect short-term rather than long-term consequences. Perceived
      short-term consequences of risk-taking behaviour were predictive of risk
      participation, however long-term consequences were not. The study provided data
      about adolescent risk-taking which mirrored and extended the findings of self
      report studies.

PMID- 9268413
TI  - Late adolescent risk-taking: effects of perceived benefits and perceived risks on
      behavioral intentions and behavioral change.
AB  - To assess the predictive utility of perceived benefits and risks of risk-taking
      behaviors (RTBs) on behavioral intentions and behavioral change, data were
      collected from 187 male and female late adolescent college students (ages 17-20).
      Perceived benefits, perceived risks, behavioral intentions, and involvement for
      18 RTBs were assessed at T1 and T2 (3 months later). Factor analyses were
      performed on T1 involvement data, and six RTB factors emerged: Alcohol RTBs,
      Illegal Drug RTBs, Stereotypic Male RTBs, Social RTBs, Sex RTBs, and Imprudent
      RTBs. Regression analyses indicated that perceived benefits accounted for
      significant variance in behavioral intentions for each of the six factors and
      Overall RTB; perceived risks accounted for significant variance in behavioral
      intentions for five of the factors. Similar regression analyses indicated that
      perceived benefits accounted for significant variance in behavior change (over a
      3 month period) for each of the six factors and the Overall RTB score, whereas
      perceived risks accounted for significant variance for only one factor (Illegal
      Drug RTBs). The result suggest that, among late adolescents, perceived benefits
      are better determinants of behavior change for RTBs than are perceived risks.
      Both perceived benefits and perceived risks, however, are important determinants
      of behavioral intentions. These findings support previous work identifying
      adolescents as "sensation seekers". Interventions should address perceived
      benefits of RTB, rather than relying solely on promoting knowledge of the risks.
      Assessment of adolescent RTB should continue to use multi-item measures to obtain
      a broad picture of the variety of behaviors commonly endorsed by adolescents.

PMID- 9268414
TI  - The development of forgiveness in the context of adolescent friendship conflict
      in Korea.
AB  - A developmental pattern of understanding interpersonal forgiveness is proposed
      and examined with 30 junior high and 30 college students in Seoul, Korea. Three
      questions are asked: Does the developmental sequence in understanding forgiveness
      relate to age? Is there a relation between the understanding of forgiveness and
      the degree of forgiveness offered to one's offending friend? Is there a relation
      between the way people understand forgiveness and how they go about restoring an
      actual friendship in conflict? All participants had serious and unfair conflicts
      with their close friends during the past 5 to 6 months. Results support a
      developmental sequence in Korea and the observed relation between the sequence
      and actual friendship restoration strategies. There was at least partial
      statistical support for the relation between understanding forgiveness and the
      participants' forgiving behaviour in real life situations. Implications are drawn
      for the study and implementation of forgiveness in adolescents.

PMID- 9268416
TI  - The Family Project Approach.
AB  - The Family Project Approach (FPA) has been developed as an alternative to the
      placement of conduct-disordered adolescents into care. Since 1987, the target
      group of this project has been extended to include maltreated children and to
      parents who are in despair because of persistent child behaviour problems and
      other stressors. This article gives an overview of this home-based approach and
      the most important research results. One main starting point for FPA is that
      parents should be supported so that they can fulfil their child-rearing
      responsibilities. In families where the children are neglected or maltreated and
      in families where the parents feel desperate and powerless, the fundamental
      attitude of the FPA worker plays a decisive role. Process-outcome research
      corroborates the importance of encouraging and validating the parents' positive
      qualities and expertise.

PMID- 9268415
TI  - The influence of puberty, family processes, and leisure activities on the timing
      of first sexual experience.
AB  - This study investigated the effects of pubertal timing, demographics, family
      processes, and leisure activities on the timing of first sexual experience. The
      sample included 15-18-year-old adolescents from the former East and West
      Germanys. Hierarchical model using Cox regression examined the differences in the
      patterns of predictors by nation and sex. Higher levels of parental monitoring
      predicted later initiation of sexual experience for West males and females and
      East males. In the final model pubertal timing was significant only for East
      males. Higher levels of risky leisure predicted earlier first sexual experience
      for East males and females and West females. Social-romantic leisure was a
      significant predictor of earlier timing for both West males and females.

PMID- 9268417
TI  - Adolescents' perceptions of their parents' disclosure to them.
AB  - This study examines 144 older adolescents' perceptions of their parents'
      disclosure of their own lives to them. Information was obtained about the
      disclosure of 209 parents of college-aged children. The adolescents indicated
      whether and to what depth their parents had discussed 30 topics with them, and
      also indicated why they believed their parents had made these disclosures. The
      data indicate that college-age adolescents believe that their mothers disclose
      more to them than their fathers, especially about their problems. Mothers were
      also perceived to disclose for different, more emotional reasons than fathers,
      and they were perceived to seek advice more often.

PMID- 9268418
TI  - Life satisfaction among low-income rural youth from Appalachia.
AB  - The purpose of this study was to examine the relative strength of objective,
      subjective, and congruency variables as predictors of life satisfaction among low
      income youth from rural areas. A 10-year longitudinal survey of low-income, rural
      youth from Appalachia (n = 322) was conducted to explore these issues. Although
      support was provided for variables representing all three types of life
      satisfaction predictors, the strongest of these were subjective variables such as
      self-perceptions about goal attainment in jobs, overall goal attainment in life,
      and self-esteem. Another set of consistent predictors of life satisfaction,
      congruence variables, were concerned with the extent to which low-income you
      believed that they had fulfilled their own aspirations in terms of formal
      education, proximity to their childhood homes, and number of children, Finally,
      some of the objective variables consisting of family of origin's SES, community
      size, and marital status also were predictive of life satisfaction. In general,
      the life satisfaction of low-income, rural youth seemed to be influenced more
      extensively by personal meanings shaped within a particular cultural context
      rather than by traditional objective measures of life circumstances.

PMID- 9268419
TI  - Personality and risk-taking: a brief report on adolescent male drivers.
AB  - Risky driving is a major contributing factor in adolescent injuries and deaths,
      particularly for young males. In the present study, the relationship between
      personality characteristics and increased crash risk was investigated by
      comparing scores of high- and low-risk drivers on the Personality Research Form
      and the Jackson Personality Inventory. The role of personality factors in
      accident risk is discussed in terms of different theoretical accounts of
      adolescent risk-taking.

PMID- 9268420
TI  - Absence of a salt (NaCl) preference or appetite in sodium-replete or depleted
      kittens.
AB  - Many omnivores and herbivores exhibit an appetite for sodium or salt (NaCl)
      solutions, but a similar sodium appetite has not been demonstrated in carnivores.
      The choice for or against sodium-adequate diets of sodium-replete and depleted
      kittens (confirmed by an elevated plasma aldosterone concentration) was examined
      using a two-bowl choice test. Both bowls contained purified diets, one bowl with
      one of various levels of sodium (as NaCl) and the other bowl a sodium-deficient
      diet (0.1 g Na/Kg). Neither sodium-replete nor depleted kittens showed a choice
      of the diet containing 2 g Na/kg over the deficient diet. Both groups of kittens
      showed significant aversion to a diet containing 10 g Na/kg diet, with no change
      in total food intake. Kittens previously exposed to a diet containing 10 g Na/kg
      diet appeared to have a learned aversion to sodium in subsequent choice tests. We
      conclude that kittens do not possess an innate sodium appetite and that a sodium
      appetite is not induced in sodium-depleted kittens.

PMID- 9268421
TI  - Meal pattern and nutrient intake among adult Finns.
AB  - The purpose of this study was to investigate the relationship between meal
      pattern and diet. Nutrient contents of meals, snacks and other eating occasions
      were compared and differences in dietary intake analysed between respondents
      following a conventional meal pattern and others. A random sample of 1861 adults
      aged 25-64 from four regions of Finland completed a mailed questionnaire and 3
      day food record in the spring of 1992. A conventional meal pattern was defined on
      the basis of national dietary guidelines as including breakfast, warm lunch and
      warm dinner, and subjects were identified with the help of the questionnaire.
      Meals and snacks were defined according to the respondents subjective criteria.
      Forty-four percent of all respondents followed the conventional meal pattern.
      Meal pattern has no effect on nutrient intake in men and small effects in women.
      Women following the conventional meal pattern had higher energy and cholesterol
      intake and lower alcohol and vitamin C intake than other women. Meals contributed
      to energy, protein and fat intake, and snacks to sugar and alcohol. Meal pattern
      had only a small effect on diet and conventional meal pattern cannot be
      considered healthier than other meal patterns.

PMID- 9268422
TI  - Social effects on duration in restaurants.
AB  - A nonreactive observational study in full-service restaurants showed group size
      to be positively correlated with length of stay. Among the serendipitous findings
      were the role of reading in lengthening duration and the paucity of lone diners
      in full-service restaurants.

PMID- 9268423
TI  - Effects of temperature and volume on measures of mouth dryness, thirst and
      stomach fullness in males and females.
AB  - The immediate post-ingestive effects of temperature on thirst reduction were
      explored. Thirst was assessed by both ratings and a volume selection task.
      Supplementary ratings assessed mouth dryness and stomach fullness. All measures
      were taken before and 0, 2.5 and 5 min after drinking one of four water samples
      (150 ml/5 degrees C, 400 ml/5 degrees C, 150 ml/22 degrees C or 400 ml/22 degrees
      C). After 2.5 min, the cold sample produced greater reductions than the warmer
      sample in (i) the thirst ratings of males who received 400-ml samples, and (ii)
      the volume selections of females who received 150-ml samples. It is proposed that
      temperature influenced thirst reduction because of its differential effects on
      the post-ingestive state of the mouth.

PMID- 9268424
TI  - Body dissatisfaction as a mediator of the relationship between dietary restraint
      and bulimic eating patterns.
AB  - The present study was designed to test whether dietary restraint mediates the
      relationship between body dissatisfaction and bulimic eating patterns in a sample
      of 172 university females. Contrary to what was expected the results showed that
      body dissatisfaction mediated the relationship between dietary restraint and
      bulimic patterns of eating. Thus the results highlight the primary importance of
      body dissatisfaction as a predictor of bulimic behavior. Body dissatisfaction
      encompasses a broad array of dimensions such as self-perceptions, cognitions,
      affect and behavior and it carries enormous explanatory power but its different
      components remain largely unexplored.

PMID- 9268425
TI  - Eating frequency in the Nationwide Food Consumption Survey (U.S.A.), 1987-1988.
AB  - This study was done to provide basic descriptive data on the variation in meal
      frequency in the U.S. The data analysed were from the 1987-1988 Nationwide Food
      Consumption Survey (NFCS), a stratified random sample of American households.
      Participants were asked to provide one 24-h diet recall and two 1-day diet
      records. Individuals who were pregnant, lactating, or younger than 19 years old
      were excluded. If more than one eligible subject per household participated, one
      subject was selected at random. Of the 4,078 eligible participants, data for
      3,182 were complete for all three days and were included in the analyses. On
      average participants ate 3.47 times daily (SD 0.90). When eating occasions during
      which 70 or fewer kcal were excluded (tea, coffee, or diet beverages, primarily),
      the mean was 3.12 (SD 0.74), and over 90% of subjects ate between 1. 50 and 4.49
      times daily. The ratio of within- to between-person variance in number of eating
      times daily was 1.17 (</=70 kcal excluded). The day-to-day variation in an
      individual's eating frequency was relatively large compared with the between
      subject variation, suggesting that data for multiple days are needed to measure
      an individual's eating frequency with precision.

PMID- 9268426
TI  - Independent effects of palatability and within-meal pauses on intake and appetite
      ratings in human volunteers.
AB  - The effects of the introduction of timed pauses within meals and palatability on
      food intake and changes in rated appetite during a meal were assessed in three
      experiments in which volunteers ate a lunch of pasta with a tomato sauce. Eating
      was monitored using a disguised electronic balance attached to a micro-computer,
      which also allowed the introduction of timed pauses within meals. In the first
      experiment, 16 subjects were tested with both a bland and palatable food (with
      0.27% oregano), with eating uninterrupted or with pauses after every 50 g
      consumed during which appetite ratings were completed. Both the addition of
      oregano and the introduction of regular within-meal pauses enhanced overall
      intake. Rated hunger increased in the early stages of eating the palatable food
      in the interrupted condition, and then declined, whereas hunger declined
      throughout with the bland food. Similarly, the linear function relating intake to
      time in the uninterrupted condition was greater with the palatable food. In the
      second experiment, nine subjects ate the palatable food with no pauses within
      meals, with 30-second pauses with appetite ratings or with 30-second pauses in a
      non-appetite task. Intake was greater in both pause conditions than when eating
      was uninterrupted. In Experiment 3, the effect of pause duration was investigated
      in a further 16 subjects, with either no pause or a pause of 5, 30 or 60 seconds.
      Subjects ate more in all pause conditions than with no pauses, while ratings of
      hunger and fullness suggested that subjects were less satisfied at the end of the
      meal with longer pauses. These data confirm previous work which suggests that
      palatability exerts its effect by stimulating appetite and eating rate, but also
      suggest that the introduction of pauses within meals enhances intake as well,
      contradicting the idea that pausing within meals should reduce intake by allowing
      more time for post-ingestive satiety to develop.

PMID- 9268427
TI  - Effect of one week of fibre supplementation on hunger and satiety ratings and
      energy intake.
AB  - The effect of one week of supplementation with a water-soluble fibre (guar gum)
      was studied in obese women who had lost weight. In study 1 (N=17; mean+/-SEM: age
      38.5+/-2.3 yrs; weight 86.8+/-2.3 kg; BMI 32.2+/-0.9 kg.m-2) energy intake and
      hunger and satiety scores were assessed under free-living conditions. In study 2
      (N=14; age 44. 5+/-1.8 yrs; weight 78.8+/-3.1 kg; BMI 29.0+/-0.9 kg.m-2) energy
      intake was fixed at 6 MJ.day-1 (their normal energy intake at that time) or 4
      MJ.day-1 (low energy intake). In both studies, the effect of one week of fibre
      supplementation (40 g in study 1 and 20 g in study 2) was compared with no
      supplementation. In study 1, mean energy intake decreased significantly from
      6.7+/-0.4 MJ to 5.4+/-0.2 MJ daily after fibre supplementation, while hunger and
      satiety scores did not change. At a low energy intake level of 4 MJ given in
      study 2, hunger scores were significantly decreased after fibre supplementation.
      No changes were seen in hunger and satiety scores during fibre supplementation at
      6 MJ. The reduction in energy intake by soluble fibre under free living
      conditions and the hunger-reducing effect of fibre at the low energy intake level
      (4 MJ) suggests that fibre may be useful in the treatment of obesity, by
      facilitating compliance to low energy intake.

PMID- 9268428
TI  - Food and general neophobia and their relationship with self-reported food choice:
      familial resemblance in Swedish families with children of ages 7-17 years.
AB  - The aims were to study food and general neophobia in Swedish families, age and
      gender differences and familial resemblance. Also, the relationships between the
      level of food neophobia of individual family members and earlier experience with
      and the likelihood of future tasting of specific foods were investigated. A group
      of randomly selected families (nation-wide, stratified, N=1593) with children age
      7-17 years were invited and 722 participated. The results are based on the Food
      and General Neophobia Scales and an ad hoc Food Frequency Questionnaire. The
      overall levels of food and general neophobia were low. Fathers showed
      significantly higher total food neophobia scores than did the mothers, and
      children were significantly more neophobic than their parents. The younger
      children had higher food and general neophobia scores than the older children.
      Nine-year-old boys had higher food neophobia scores than 9-year-old girls. Some
      evidence was found for familial resemblance with respect to both food and general
      neophobia. Gatekeepers' (the person who takes the greatest responsibility for
      food purchase and preparation) self-reported serving of the foods and mothers',
      fathers' and children's self-reported consumption of foods were correlated with
      their respective levels of food neophobia. The strongly neophobic subjects in all
      groups of family members were less likely to have eaten the listed foods than
      were the less neophobic. Thus, food neophobia seems to be related to everyday
      food choice.

PMID- 9268429
TI  - The anorectic effect of bacterial cell wall compounds - mechanisms and clinical
      implications.

PMID- 9268430
TI  - Shell-size preference of hermit crabs depends on their growth rate
AB  - The hypothesis that hermit crabs modify their shell-size preference according to
      their prospective growth rate was examined in the hermit crab Pagurus
      middendorffiiA simple model predicts that individuals should select larger shells
      when (1) shell availability is limited, (2) they approach moulting and (3) they
      will have a large increase in size at the next moult. In experiments, selected
      shell size decreased with the duration of the moult, and increased with
      increasing growth, supporting predictions 2 and 3.

PMID- 9268431
TI  - Asymmetric territorial contests in the European robin: the role of settlement
      costs
AB  - A widespread feature of territorial systems is that residents almost invariably
      defeat challengers. This phenomenon has been explained by the existence of value
      asymmetries, variations in resource-holding potential or an 'owners always win'
      convention. Removal-replacement experiments were performed on 75 robins,
      Erithacus rubeculato test these hypotheses. The settling behaviour of newcomers
      was also examined in order to identify energetic costs incurred during territory
      establishment. In winter, dominance shifted gradually from removed owners to
      newcomers with increasing time of newcomer residence, and there was a peak in
      contest duration at 4-7 days. Removals of newcomers, followed by replacement with
      another newcomer, confirmed that dominance was determined by the time newcomers
      were in residence rather than the time original owners were absent. These results
      support the hypothesis that asymmetries in territory value govern the outcome of
      contests. It is proposed that high singing rates and low foraging rates of
      newcomers settling boundaries with neighbours contribute to this asymmetry,
      skewing outcomes in favour of original owners until replacements are fully
      established. The key result in this study is that the time at which dominance
      tends to reverse (5-6 days in winter) is predicted by the time taken for
      newcomers to settle territory boundaries and achieve base-line foraging effort.
      In spring, original owners become subordinate almost immediately after removal.
      Reductions in settlement cost for newcomers, and increases in territory value,
      are proposed to accelerate dominance reversal. Age and sex effects on dominance
      suggest that the value asymmetry rule is modified by variations in resource
      holding potential.

PMID- 9268432
TI  - Female size affects provisioning and sex allocation in a digger wasp
AB  - Investment ratios in field populations of the European beewolf, Philanthus
      triangulum F. (Hymenoptera, Sphecidae), are strongly biased towards males.
      Possible explanations are conditional sex allocation and/or constraints on
      provisioning females: daughters need at least three prey items (honey bees),
      whereas sons need only one to develop and reproduce. If small females are not
      able to procure these three bees quickly enough they might have to produce sons
      instead. Larger females had a higher proportion of successful hunting flights,
      carried heavier loads, and could fly continuously with a load for longer than
      small females. They brought in more and heavier bees but needed less time for a
      single hunting trip. An estimate of the sex allocation of the food bees, based on
      the timing pattern of successful hunting trips, suggested that female size is
      positively correlated with the proportion of daughters produced. However, this
      effect explains only a small part of the overall variation in investment ratio.

PMID- 9268433
TI  - Distribution and activity of male harbour seals during the mating season
AB  - Little is known about male reproductive strategies in aquatically mating
      pinnipeds. To study the mating patterns of harbour seals, Phoca vitulinaVHF
      telemetry was used to relate the distribution and behaviour of adult males to the
      distribution of females during the summer pupping and mating season. Prior to
      July males occupied large and variable ranges. At the beginning of July, males
      decreased their mean range size, but continued to spend much of their time in the
      water where they made characteristic short dives. Acoustic recordings in the
      presence of several radiotagged males suggested that these short dives were
      associated with underwater vocal displays. Throughout July, males varied in the
      geographical areas which they used to perform these displays. Some individuals
      were found in the water around haul-out sites; others were located on foraging
      grounds, up to 50 km from pupping sites, and some were consistently located
      displaying on transit routes between these two areas. This study supports
      previous suggestions that vocalizations and diving displays may be associated
      with male mating behaviour, but suggests that males may display over a much wider
      geographical area than was previously recognized. This system of dispersed but
      small display territories is suggestive of lekking. However, further research on
      the distribution of the clumping of displaying males is required to confirm this.

PMID- 9268434
TI  - Copulation and mate-guarding patterns in polygynous European starlings
AB  - We recorded the timing and frequency of copulation and mate-guarding behaviour
      during the fertile period in relation to day of first ovulation and time of day
      in the facultatively polygynous European starling, Sturnus vulgarisAll within
      pair copulations were female-solicited. Females solicited them at a high rate
      during both the pre-ovulatory and ovulatory period, but there were differences in
      solicitation rates between monogamous, primary and secondary females. Extra-pair
      copulation attempts were all male-initiated and females rarely engaged in them.
      Attempts by males were most frequent during the ovulatory period, when the
      probability of extra-pair fertilization was highest. Males intensively guarded
      their mate during both the pre-ovulatory and ovulatory period. In contrast to
      most other passerines, female starlings lay their eggs not at dawn but usually
      between 0900 and 1100 hours, implying that they may be most fertile in the late
      morning. During the ovulatory period, extra-pair copulation attempts were more
      frequent in the late morning than in the early morning, suggesting that males try
      to take advantage of this putative 'insemination window'. Accordingly, there was
      some indication that mate guarding during the ovulatory period was more intense
      in the late than early morning. Females solicited within-pair copulations at a
      higher rate in the early morning than in the late morning, but copulation rate
      did not differ between early and late morning. The proportion of monogamous and
      polygynous males attempting extra-pair copulations did not differ significantly,
      but mate-guarding intensity differed significantly between female categories.
      Primary females were guarded less intensively than monogamous females suggesting
      that males trade mate guarding against mate attraction/courting additional
      females.

PMID- 9268435
TI  - Nutritional correlates of reproductive success of male Mediterranean fruit flies
      (Diptera: Tephritidae)
AB  - We examined the hypothesis that adult diet affects the reproductive success of
      male Mediterranean fruit flies. In particular we determined whether protein-fed
      males copulated more frequently than protein-deprived males. Furthermore, we
      determined whether the nutritional status of their first sexual partner affects
      the renewal of female receptivity. Males fed no protein copulated at a
      significantly lower rate than did males fed protein. In both diet groups, size
      was significantly associated with copulatory success. Protein-deprived males
      transferred significantly more sperm to their mates than did protein-fed males.
      However, significantly more females mated to protein-deprived males re-mated on
      the following day. We conclude that male diet is a significant factor in
      determining male reproductive success. Male diet affects the ability to gain
      copulations with virgin females, and the receptivity of these females to further
      copulations.

PMID- 9268436
TI  - Food supply for settling male rock pipits affects territory size
AB  - Theory predicts that abundant food may favour larger breeding territories,
      provided that males could gain some important benefit, such as improved mating
      success or breeding performance, from keeping a large territory. The time saved
      when food is easy to find may be used to defend more space, unless increased
      defence costs offset the savings in foraging time. A previous experiment with
      concealed food addition close to laying did not reveal any effects on rock pipit,
      Anthus petrosusterritories. In this study the food intake rate of males was
      manipulated at the time of arrival from the winter quarters, by providing a
      concealed food source at the centre of each territory. The aim was to reduce
      foraging time, without attracting intruders, in order to isolate any effects of
      food abundance. Fed males had larger territories and tended to defend longer
      stretches of shoreline than control males. The difference in territory size was
      not related to male age or order of arrival. These results suggest that males
      settling at concentrated food sources may be able to establish large territories,
      and that keeping a large territory confers some advantage. We discuss possible
      reasons why food intake rate later during the breeding season did not affect
      territory size.

PMID- 9268437
TI  - Polygynous male starlings allocate parental effort according to relative hatching
      date
AB  - In many polygynous bird species, males allocate most of their parental effort to
      their primary females' broods. There are several hypotheses that may explain
      this: the relative reproductive value of the brood, the energetic demand of the
      brood, the genetic quality of the female and the certainty of fatherhood may all
      be higher for the primary females' broods. Since these parameters may covary in
      nature, experiments are necessary to determine their importance. Bigynous male
      European starlings, Sturnus vulgarispredominantly incubated the eggs and fed the
      nestlings of their primary females. In an experiment we altered the order in
      which the clutches hatched by exchanging the primary and secondary females' eggs
      before hatching. Even though experimental males mostly incubated their primary
      females' clutches, they predominantly fed the nestlings of the secondary female.
      Experimental males fed secondary females' nestlings significantly more than
      control males did. In fact, experimental males invested in their secondary
      females' broods to the same extent as control males invested in their primary
      females' broods. This result demonstrates that males use relative brood age to
      decide how to allocate their parental effort between their broods which has
      important implications for the evolution of the starling mating system.

PMID- 9268439
TI  - Effects of birds on the intensity of ant rain: a terrestrial form of invertebrate
      drift
AB  - Large numbers of wood ants, Formica aquiloniacrawl up trees to gather food
      (arthropods and honeydew), and most return to the ground the same way. A small
      but noticeable percentage, however, returns to the ground by falling. This
      continuous rain of free-falling ants, from trees to the ground, is analogous to
      the drift of invertebrates in freshwater streams, and provides ecologists with an
      easily replicated terrestrial system for studying the phenomenon of drift. In a
      field experiment in this system, when birds came to forage, the total numbers and
      percentages of ants entering the rain increased dramatically. Initial background
      levels of ant rain (before birds came to forage) ranged from 0 to 11.9% (X=4.0%).
      When birds came to forage in certain trees, the percentage of ants entering the
      rain in those trees ranged from 2.9 to 28.4% (X=9.1%). In trees not visited by
      birds, ant rain decreased slightly during the same period to a mean of 3.7%. As
      the total time birds spent foraging in a tree increased, ant rain there also
      increased.

PMID- 9268438
TI  - Female bluethroats prefer males with symmetric colour bands
AB  - Fluctuating asymmetry in male ornaments may be related to male quality and
      therefore may be used by females as a guide in mate choice. Experiments on
      different species have shown female preferences for symmetry, but few previous
      studies have addressed preferences for symmetry in coloration. Using the
      bluethroat, Luscinia s. svecicaa passerine with a conspicuous blue and chestnut
      throat patch, as a model species, we devised an experiment in which the females
      could choose between males with either symmetric or asymmetric coloured leg
      bands. The females associated more with symmetric than asymmetric males,
      indicating a preference for symmetry.

PMID- 9268440
TI  - Fledging in the common swift, Apus apusweight-watching with a difference
AB  - Fledging in the common swift involves young having to switch suddenly and
      completely from the sedentary lifestyle of a nestling to continuous flight with
      no post-fledging care. Using manipulations of brood size and the contrasting
      resource conditions in different breeding seasons, I observed fledging under a
      range of chick states. Poorly fed chicks took longer to fledge, and had lower
      body mass and short wing length at fledging. Despite this, maximum body mass of
      nestlings always exceeded those of adults and fledged young. Under all
      conditions, nestlings lost mass for 1 week prior to fledging, and at fledging
      they had similar wing loadings. I suggest that in their last days in the nest
      young swifts use up the fat stores that insured them against irregular parental
      provisioning as well as losing water from the drying out of feathers. Reductions
      in body mass associated with increases in wing length before fledging will affect
      flight efficiency by increasing the lift:drag ratio. This is interpreted as
      'slimming' down to the optimal body mass which would improve the lift:drag ratio
      and set fledgings up for their life on the wing.

PMID- 9268441
TI  - Why do animals repeat displays?
AB  - Both agonistic and sexual animal displays often involve more than one performance
      of some specific display action. Since repetition is energetically costly there
      must be good reasons why a signaller should carry out such repetitive actions,
      rather than simply displaying once. We briefly review three different 'reasons'
      which arise from three different receiver assessment rules: when assessment is
      based on the average magnitude of all display actions so far, the reason for the
      repetition is to improve the accuracy of the estimate (model A); when the
      assessment is based solely on the action of greatest magnitude so far, the
      repetition is to replace the signal with one of greater magnitude (model B); when
      the assessment is based on the cumulative sum of all display actions so far, the
      repetition is to augment that sum (model C). We discuss how to characterize each
      case from an understanding of its expected optimal behaviour as predicted by
      formal models. For model A the mean magnitude of display actions should stay
      constant and the contest duration should depend on relative qualities. In models
      B and C the encounter duration depends only on the weaker participant. In model B
      each display action is greater than the previous, but only a small number of
      steps are expected. In model C the magnitude of display actions can either
      escalate, stay constant, or even decrease. The displays of cichlid fish, the
      roaring contests of red deer, Cervus elaphusthe calling of Blanchard's cricket
      frogs, Acris crepitans blanchardiand the pheromonal exchanges of yeast gametes
      are used as illustrative examples.

PMID- 9268442
TI  - Coloured leg bands affect male mate-guarding behaviour in the bluethroat
AB  - Artificial traits such as coloured leg bands may affect an individual's mating
      success, as shown for some birds. One explanation is that colour-matching with a
      sexual ornament affects the individual's sexual attractiveness. This study
      reports a colour-band experiment with free-living bluethroats, Luscinia s.
      svecicaa species where males have a distinct blue and chestnut throat and upper
      breast. There was no apparent difference in pairing success between males with
      ornament-matching colour bands (blue and orange) and males with non-ornamental
      colour bands. However, males with ornamental bands guarded their mates less
      intensely and spent more time singing, performing song flights and intruding into
      neighbours' territories than males with non-ornamental bands. We conclude that
      colour bands affect the trade-off between mate guarding and advertisement
      behaviour in a way that is consistent with the hypothesis that bands with
      ornamental colours improve a male's attractiveness. The results are in
      concordance with a previous study of the same population, showing that males with
      experimentally reduced attractiveness guarded their mates more closely and
      advertised less for additional mates, than non-manipulated males.

PMID- 9268443
TI  - Ontogeny of vocal signals in the little brown bat, Myotis lucifugus
AB  - This study reports developmental changes in the vocal signals produced by wild
      caught pre-volant and volant Myotis lucifugusAudio recordings were made from
      young animals (1-33 days old) and adults (over 1 year of age). The animals were
      removed from an attic maternity roost and studied individually in a room below.
      To stimulate flight-related behaviours, animals were released from a launching
      platform via a hinged floor, and their vocalizations were recorded as they
      approached a soft foam pad below. When the hinged floor opened, the youngest
      animals (1-4 days old) typically dropped onto the pad, but older animals either
      flapped their wings to achieve some horizontal displacement (>4 days) or
      sustained horizontal flight (>17 days). Vocalizations recorded under these
      conditions showed frequency modulation characteristic of adult echolocation
      sounds, even in animals as young as 4 days. Ontogenetic trends showed an increase
      in sound frequency, an increase in sound repetition rate and a decrease in sound
      duration as the animals matured. These data are discussed in the context of the
      development of echolocation behaviour in bats.

PMID- 9268444
TI  - How robins find worms
AB  - An understanding of diet selection in animals requires knowledge of not only what
      animals eat in relation to what is available, but also how they perceive the
      foods available to them. Birds use auditory, visual, olfactory and possibly
      vibrotactile cues to find prey, but vision is the predominant mode of prey
      detection. In a series of controlled experiments in an aviary, four American
      robins, Turdus migratoriusfound buried mealworms in the absence of visual,
      olfactory and vibrotactile cues, suggesting that they could use auditory cues to
      locate the prey. They also had significantly reduced foraging success when
      auditory cues were obscured by white noise. These results conflict with the only
      other experimental study of foraging in American robins, which concluded that
      they foraged using visual clues alone.

PMID- 9268445
TI  - Clutch desertion and re-nesting in pied flycatchers: an experiment with
      progressive clutch removal
AB  - Clutch desertion and re-nesting are important components of fitness when
      predation is frequent. In nestbox populations however, nest predation and
      desertion are rare but can be studied by experimental manipulations. We
      experimentally reduced clutches of pied flycatcher, Ficedula hypoleucaby removing
      one egg per day until desertion occurred. The size of the clutch at desertion and
      whether females re-nested or not were used as measures of the female response. Of
      the deserting females, 74% re-nested in our study area. Re-nesting frequency was
      correlated with date but not with the size of the clutch laid. The majority of
      the non-re-nesting females deserted empty nests, while the majority of re-nesting
      females deserted one egg. Clutch size at desertion was not correlated with the
      size of the clutch laid nor with laying date; it was smaller than the size
      predicted by an optimality analysis of the value of both the current (deserted)
      and the replacement clutch. For the re-nesting females, there was a negative
      correlation between fledging rate of the replacement clutch and the size of the
      clutch at desertion. Our predictions, made under the hypothesis that desertion
      and re-nesting are adaptive behaviours, were partly supported by the data; we
      explain the discrepancy by the constraint of searching for a new nest site or
      mate for re-nesting.

PMID- 9268446
TI  - Advantages of biparental care in the wood-dwelling termite, Zootermopsis
      nevadensis
AB  - A field experiment conducted on 49 young termite colonies lends support to the
      hypothesis that ecological constraints on successful offspring production favour
      two-parent care. Colonies cared for by two parents were twice as likely to
      survive the six-month experiment as were colonies headed by single parents. Among
      surviving colonies, the percentage change in the number of offspring did not
      differ between colonies headed by two parents versus single parents. Workers
      (third instar juveniles and older), but not non-workers (first and second instar
      juveniles), were found in all surviving colonies, indicating that offspring
      survivorship, not new offspring production, accounts for difference in success of
      two parents and single parents. Three of the four surviving single-parent
      colonies became two-parent colonies by the end of the experimental period: in two
      colonies, offspring became replacement reproductives; in the third colony, an
      adult male re-paired with a nest-founding female. Conspecific pressures from new
      nest-founding adults that flew onto logs containing the experimental colonies may
      account for high mortality in all colony types. New nest-founding pairs settled
      near experimental colonies. The mean numbers of new nest-founding pairs per
      experimental-colony area were significantly positively correlated with the
      proportion of single-parent colony failures in that area.

PMID- 9268447
TI  - Group size and aggression: 'recruitment incentives' in a cooperatively breeding
      primate
AB  - In many cooperatively breeding birds and mammals, group size is positively
      correlated with reproductive success. In marmoset and tamarin monkeys, species
      that display cooperative breeding, the presence of helpers appears to be critical
      for offspring survival, and breeders might be expected to display social
      strategies that would regulate group size. This study investigated the
      association between group size and aggression towards strangers in Wied's black
      tufted-ear marmosets, Callithrix kuhlifrom small groups (with no helpers present)
      and large groups (with helpers present). Residents were exposed to multiple
      presentations of male and female strangers. Breeding females from large groups
      spent more time in close proximity to strangers, showed higher levels of
      agonistic displays and engaged in higher levels of aggressive behaviour towards
      intruders than did breeding females from small groups. Breeding male behaviour
      did not dramatically differ as a function of group size. After the removal of the
      intruder, female breeders from large groups showed higher levels of scent-marking
      relative to baseline observations, and time spent in close proximity to the
      partner increased after exposure to female intruders in large, but not small,
      groups. The results reveal that breeders from small groups are tolerant of
      strangers, which may facilitate the recruitment of additional group members,
      whereas breeders from large groups, particularly females, are intolerant of
      strangers, which may inhibit immigration. These findings have implications for
      understanding mechanisms that regulate immigration in cooperatively breeding
      animals, and suggest of how breeders from small groups might reconcile the
      serious limitation of having few or no helpers.

PMID- 9268448
TI  - Vocal behaviour of the frog Eleutherodactylus antillensison the British Virgin
      Islands
AB  - The vocal repertoire of male Eleutherodactylus and the communicative significance
      of two calls (trill and courtship call) were investigated under natural
      conditions on the British Virgin Islands. Interspersed with two-note
      advertisement calls, males uttered trill calls, which typically consisted of an
      introductory note followed by five to 13 rapidly repeated notes. The introductory
      note and the repeated notes were within the range of the dominant frequencies of
      the first and second note of the advertisement call, respectively, but their mean
      frequencies were 5-8% higher. The temporal and spectral characteristics of the
      trill and advertisement calls were similar on three islands (Tortola, Virgin
      Gorda, Guana), except that the number of repeated notes in the trill was higher
      on Guana. Body size and air temperature had no detectable effects on the call
      characteristics. In response to experimental playback of trill calls (either
      synthesized or constructed from actual calls), males produced more trills in the
      period following the stimulus than during the baseline. During the playback
      itself, five or 22 males produced an unusually high number of trills that
      alternated with the stimulus trills. These responses suggest that the trill is an
      aggressive call used in the defence of a calling territory. In response to the
      playback of courtship calls (multi-note calls that males uttered only in the
      presence of a female and that differed from the trill call mainly in the dominant
      frequency of the repeated notes), 11 of 28 males left their perch sites and nine
      approached the speaker. In contrast, males never left their perches during the
      baseline or the trill stimulus. These responses suggest that males may exploit
      the courtship calls of rivals to obtain mates through interference.

PMID- 9268449
TI  - Nest-vicinity song exchanges may coordinate biparental care of northern cardinals
AB  - In species with biparental care, communication between the parents may increase
      the efficiency and decrease the risks of care delivery. In northern cardinals,
      Cardinalis cardinalisthe female's singing from the nest may provide information
      that allows her conspicuous mate to target his visits to the nest to times when
      food is needed, saving energy and flights that may attract nest predators.
      Thirteen pairs of cardinals were recorded in 25 nestings over six summers in
      Madison, Wisconsin, U.S.A. When a male with nestlings sang or called within 12 m
      of the nest, his probability of bringing food to the nest varied with his mate's
      response. The male was more likely to come to the nest when the female sang than
      when she did not, unless she responded to the male's song with a matching song
      type. Most males were least likely to come to the nest when their mates matched
      their songs.

PMID- 9268450
TI  - Evidence for an important social role of allogrooming in a platyrrhine primate
AB  - Allogrooming behaviour was analysed in a wild group of tufted capuchin monkeys,
      Cebus apellain Iguazu National Park, Argentina. Evidence is provided that
      allogrooming in this platyrrhine species serves an important social function, as
      has been demonstrated for catarrhine primates. Using ad libitum sampling, 654
      grooming sessions were recorded during 740 contact hours with one group. Seasonal
      variation was found in daily time allocation to allogrooming and the mean
      duration and reciprocity of sessions. Individual dominance rank was an important
      determinant of grooming relationships. The dominant male and female were the most
      actively involved in grooming. Among adults, dominant individuals were involved
      in more sessions than were subordinate individuals. The females maintained strong
      grooming relationships with each other and tended to reciprocate more within
      sessions than did males. Oestrous females engaged in more grooming bouts with
      adult males than did non-oestrous females. Females with newborn infants were
      attractive social partners for the remaining members of the group. A social
      function for allogrooming in Cebus is indicated by the close relationship between
      allogrooming, the social system and coalition formation, and by the changes in
      quantity and direction of grooming in response to oestrous behaviour and to the
      birth of infants.

PMID- 9268451
TI  - Body size and agonistic experience affect dominance and mating success in male
      copperheads
AB  - Fighting behaviour in adult male copperheads, Agkistrodon contortrix (Serpentes,
      Viperidae), was investigated in the laboratory to assess the relative importance
      of body size and type of agonistic experience as determinants of dominance and
      mating success. Seven experiments were conducted. In each experiment, trials were
      run using two adult males and one female in a large arena. The first experiment
      tested the influence of body size. All males tested had no recent fighting
      experience for 6-12 months, and one male of each pair was 8-10% longer in snout
      vent length and had greater mass. In all cases, larger males won fights and were
      first to locate, court and guard females; thus, larger snout-vent length was an
      important determinant of fighting success and priority of access to potential
      mates. Males with either winning or losing experience from the first experiment
      were used in six subsequent experiments on the relative importance of snout-vent
      length and agonistic experience in attaining dominance and mating success. Losing
      experience had a greater effect than snout-vent length on subsequent fighting
      success and gaining priority of access to females. Winning experience, in
      contrast, did not increase the probability of winning subsequent fights; however,
      winners appeared more excitable and none deferred from challenges of other males.
      The asymmetry in effects of single experiences of victory and defeat is
      consistent with studies on other vertebrates and supports the hypothesis that
      losing fights in males negatively affects behaviour directly related to their
      fitness.

PMID- 9268452
TI  - Handicap signal selection is not selection for inefficiency
AB  - No Abstract

PMID- 9268453
TI  - A reply to John
AB  - No abstract

PMID- 9268454
TI  - Refuge use and predation risk in a desert baboon population
AB  - Baboons face a serious threat of predation from leopards, Panthera pardusand
      lions, Panthera leoSince trees and cliff faces provide safety from these
      predators, baboons might use such refuges in order to reduce predation risk. This
      hypothesis was explored in a study of four groups of chacma baboons, Papio
      cynocephalus ursinusin a desert population in Namibia (groups ranged between 22
      and 55 individuals with one to six adult males). All baboons spent most of their
      time close by refuges and little time distant from them. This pattern was most
      accentuated among females in smaller groups. These females spent more time on
      refuges primarily as a result of greater refuge use during resting and grooming.
      This pattern was less clear during feeding and travelling, apparently owing to
      the constraints on refuge use imposed by the nature of these activities. A
      comparison of refuge use in high-risk and low-risk habitats (after the
      confounding effects of habitat-specific refuge availability had been removed)
      suggests that baboons might adopt one of two strategies in high-risk areas; if
      refuges are widespread they will use refuges more intensively, but if refuges are
      scarce they will adopt a time-minimizing strategy to leave the area as rapidly as
      possible. The baboons also increased their vigilance when refuges were distant.
      These results are consistent with the hypothesis that baboons use refuges to
      reduce predation risk.

PMID- 9268455
TI  - Behaviourally mediated sexual selection: characteristics of successful male black
      grouse
AB  - Recent studies of lekking animals suggest that a suite of characters may be
      favoured by sexual selection. Examples of such traits are high survival,
      increased androgen levels, territory features and morphological characters
      including exaggerated morphological ornaments. Here we argue that such selection
      is often mediated by behavioural differences and we use results from a field
      study of lekking black grouse, Tetrao tetrixas an example of our argument. In the
      absence of females, males display a range of stereotyped behaviours including
      vocalizations, visual displays and fighting. When females attend the lek, the
      behavioural repertoire of the males becomes more limited. Time budget analyses
      reveal that in the vast majority of cases, males in the presence of females
      perform only three types of behaviour: a vocal display called rookooing; a
      courtship behaviour called circling; and fighting. This suggests that female
      preference could be based on male courtship and fighting behaviour while females
      visit individual male territories and that displays not used in the presence of
      females could be ruled out as important for female preference. Sexual selection
      in black grouse, however, is a complex interplay between male-male competition
      and female choice and therefore female preference is not the only determinant of
      male success. Successful males were more often involved in fights in the absence
      of females on the lek and defended territories that were larger than expected.
      Therefore, we hypothesize that differences in male fighting ability result in
      some males occupying relatively large territories at the centre of the leks.
      Relatively large territories seem to be needed for successful courtship.
      Therefore behavioural differences mediate differences in male copulation success
      both through female preference and male-male competition.

PMID- 9268456
TI  - Fluctuating asymmetry and copulation success in lekking black grouse
AB  - In lekking black grouse, Tetrao tetrixmales at the centre of the leks obtain more
      copulations than males at the edges. We found that males with territories at the
      edge of the lek obtained fewer matings and also have the most asymmetric tarsi.
      However, when considering the tail ornament (the lyre) no correlation between
      asymmetry and mating success was found. Although females are unlikely to select
      males on the basis of tarsus symmetry, asymmetry in this trait may reflect male
      condition. We suggest that males in poor condition, as reflected by higher levels
      of fluctuating asymmetry in the tarsi, do not achieve central positions on the
      lek arena. This would account for the lower success of males with higher levels
      of fluctuating tarsus asymmetry.

PMID- 9268457
TI  - Size-assortative shoaling in fish: the effect of oddity on foraging behaviour
AB  - Current theory predicts that fish should show size-assortative shoaling in order
      to avoid increased predation risk by being the odd one out (oddity effect), or in
      order to minimize competition for food. I investigated with three-spined
      sticklebacks, Gasterosteus aculeatusthe importance of the oddity effect in
      promoting size-assortative shoaling. The greater an individual assesses its
      predation risk the less actively it is likely to forage. Hence, I examined with
      small and large fish whether an individual's foraging activity depends on its
      appearance (size) in relation to that of others in a shoal. The shoals were
      composed of three, six and 12 fish. Either one individual deviated in size from
      the rest of the shoal members or all the fish in a shoal were of similar size.
      When a stickleback was larger than others in the shoal its foraging activity was
      lower than that of large individuals in a shoal dominated by large fish or those
      in a size-assorted shoal. Small sticklebacks, however, did not change their
      foraging activity on the basis of their appearance in a shoal. These responses of
      individuals to their appearance did not depend on shoal size nor on the presence
      or absence of a predator. The results suggest that the oddity effect is likely to
      prevent larger sticklebacks from joining shoals of smaller individuals. They also
      suggest that factors other than the oddity effect, potentially food competition,
      may be more important in leading individuals to avoid the company of larger ones
      and prefer shoaling with matching conspecifics.

PMID- 9268458
TI  - Social stimulation and regulation of body mass in female starlings
AB  - The influence of consexual social stimulation on the regulation of body mass in
      female European starlings, Sturnus vulgarisduring reproductive development was
      examined. Twenty-four pairs of birds were housed in three social stimulation
      treatments: (1) control, where birds were housed in visual isolation from their
      partner; (2) visual contact, pairs of birds were separated by a clear Perspex
      screen, preventing direct physical contact, but allowing birds to view each
      other; (3) complete contact, pairs of birds were housed with no intervening
      divider, allowing full interactions between birds. The influence of these
      treatments on gonadal development, body mass and energetic reserves was examined.
      The manipulation did not significantly influence degree or rate of gonadal
      development, but did influence total body mass; birds from the complete contact
      group increased body mass to a greater extent than the other groups. This between
      group difference was attributable to changes in lean mass, rather than energetic
      reserves. However, within the complete contact group, subdominants increased
      their energetic reserves more than dominants. These results are, in part,
      consistent with differences in competition for food between the treatment groups
      influencing mass regulation, although changes in activity levels may also be
      important. Unlike previous studies, these results suggest that the social
      environment may influence the regulation of lean mass in addition to energetic
      reserves.

PMID- 9268459
TI  - Direction of predator approach and the decision to flee to a refuge
AB  - How close should an animal allow a potential predator to approach before fleeing
      to a refuge? Fleeing too soon wastes time and energy that could be spent on other
      important activities, but fleeing too late is potentially lethal. A model to
      predict flight initiation distance was developed, based on the assumption that
      animals would flee at a distance that allows them to reach the refuge ahead of
      the predator by some margin of safety. This model predicts that (1) flight
      initiation distance should increase with distance from the refuge (which has been
      supported by studies on several species) and (2) the rate of increase of flight
      initiation distance with distance from a refuge should be higher when the refuge
      is between the predator and prey (prey runs towards the predator) than when the
      prey is between the predator and the refuge (prey runs away from the predator).
      Prediction 2 was tested by approaching juvenile woodchucks, Marmota monaxalong an
      imaginary line between the animal and its burrow entrance and measuring the
      distance between the observer and the animal at the moment it started its flight.
      As predicted, the rate of increase in flight initiation distance was higher when
      the burrow was between the observer and the woodchuck than when the woodchuck was
      between the observer and the burrow. The slopes were appropriate for predators
      with pursuit speeds about twice the escape speed of the woodchucks. The
      difference between the slopes was 1.78 m flight distance/m distance to refuge,
      close to the value of 2 m flight distance/m distance to refuge predicted by the
      model. The intercept indicated that woodchucks allowed a margin of safety of
      about 7.6 m. The model permits quantitative evaluation of the principal elements
      of flexible escape decisions of animals and provides a measure of how predation
      risk increases the cost of space use in relation to distance from a refuge.

PMID- 9268460
TI  - Infanticide in great reed warblers: secondary females destroy eggs of primary
      females
AB  - In 1994-1995 artificial nests with attached model eggs were put into territories
      that were known to have been occupied by male great reed warblers, Acrocephalus
      arundinaceusin previous years. Because the eggs were made of soft plasticine,
      predators left peckmarks in them and this enabled us to identify predators by
      comparing peckmarks with reference marks made by various species. Previous field
      data had suggested that infanticidal behaviour existed in our study population,
      as nests of primary females suffered a three times higher rate of nest loss
      during the egg-laying period than nests of secondary and monogamous females. The
      presence of infanticide was supported by the experiment. Small peckmarks
      resembling those of a great reed warbler occurred almost exclusively in
      territories occupied by great reed warblers, in particular when a new female
      settled in the territory. The newly settled females built nests closer to
      depredated than non-depredated nests. That small peckmarks occurred when new
      females settled strongly suggests that it is secondary female great reed warblers
      that commit infanticide on eggs of primary females. Females of low harem rank are
      expected to gain from infanticidal behaviour because a low ranked female gets a
      higher proportion of male parental investment when the nest of the primary female
      fails.

PMID- 9268461
TI  - Infanticide by males in a spider with suicidal maternal care, Stegodyphus
      lineatus (Eresidae)
AB  - Infanticide by males in species with high maternal investment may be the most
      extreme example of a reproductive conflict of interests between males and
      females. The subsocial spider Stegodyphus lineatus is semelparous, and the
      offspring eat their mother. Male and female maturation overlap, such that late
      maturing males encounter females that are already guarding the single clutch. A
      late male may try to remove the existing egg sac, thereby forcing the female to
      replace the clutch and use his sperm to fertilize at least some of the eggs.
      Males were responsible for 33% of all the egg losses in a population of 278
      females with eggs. By losing her clutch, the female loses time equivalent to the
      age of the lost clutch plus the time it takes to replace it. The earlier in the
      season a female lost a clutch and the younger the eggs were, the longer was the
      interval between clutch loss and clutch replacement. Females that lost their egg
      sacs by infanticide replaced them after a significantly longer time than females
      that lost their egg sacs from other causes. The time loss of 18.5 days on average
      corresponds to a 23% reduction in female survival probability. In addition to
      reduced survival, females suffered a fecundity cost: replacement clutches were
      smaller than the original clutches and the reduction in egg number was greater
      with increasing intervals between the first and second clutch. Females defended
      their egg sacs aggressively against males. In field tests, the outcome of fights
      between males and females was determined by the relative size difference of the
      contestants. The mating system of S. lineatus provides an example of a male
      mating strategy that evolved despite being very costly for the females.

PMID- 9268462
TI  - Assessment of pre-laying motivation in the domestic hen using social interaction
AB  - While much is known about the hormonal basis of pre-laying behaviour of domestic
      hens, Gallus gallus domesticuslittle is known about how the behaviour is
      initiated or how changes in this behaviour occur. An experiment was conducted in
      which hens had to overcome an aversive task, during the course of pre-laying
      behaviour, in order to reach a nest site. Twelve hens were tested in four
      treatments presented as a Latin square design. The test arena was arranged such
      that hens could approach the nestbox only along one corridor, and return to the
      home pen by another. The four treatments consisted of leaving the corridor
      leading to the nestbox empty, or placing a hen that was dominant, subordinate or
      unfamiliar to the test-bird in it. Hens took longer to enter the corridor leading
      to the nestbox when there was a dominant or unfamiliar stimulus-bird than with a
      subordinate or an empty corridor. They also made more attempts to find
      alternative routes to the nestbox during the searching phase of pre-laying
      behaviour when there was a dominant or unfamiliar stimulus-bird, than with a
      subordinate stimulus-bird or empty pen and made fewer entries into the corridor
      with an unfamiliar stimulus-bird, but not a dominant or subordinate stimulus-bird
      or an empty pen. We suggest that hens are weakly motivated to reach the nest site
      during the searching phase. However, the motivation to gain access to a nest site
      increases near the start of the sitting phase of pre-laying behaviour.

PMID- 9268463
TI  - Path integration by swimming rats
AB  - Path integration is a process that enables a moving animal to memorize the
      location of the starting point of its outward path relative to its current
      position by continuously processing motion-related information collected en route
      (route-based information). There has been no evidence, however, that path
      integration could be used by a swimming animal, even in aquatic or amphibious
      species. I conducted water maze experiments to test whether rats, Rattus
      norvegicuscan rely on path integration while swimming, in order to return to a
      hidden escape platform after circular outward paths ranging from 60&deg; to
      300&deg;. Rats proved able to perform the task in a few days. No systematic
      errors in the distribution of return directions could be observed. In contrast,
      there was a fairly large random error (about 55&deg;), which, surprisingly, did
      not depend on the outward path length. Comparison with walking rats could not be
      made because of the lack of published data. However, results for walking
      hamsters, Mesocricetus auratusshowed that their random errors are slightly
      smaller than those made by swimming rats. Such large errors are likely to prevent
      rats as well as hamsters (and presumably any swimming or walking mammal) from
      using path integration over long outward paths.

PMID- 9268464
TI  - Straight-line movement and competitive mate searching in prairie rattlesnakes,
      Crotalus viridis viridis
AB  - Males compete in various ways for mating and reproductive success. Phylogenetic
      factors and local ecology affect female spatial and temporal distributions, which
      in turn influence the form of male competition, sexual selection and mating
      systems. In prairie rattlesnake, Crotalus viridis viridispopulations where (1)
      males seek females during a brief reproductive period, (2) females are relatively
      few, and (3) females are widely and unpredictably distributed spatially into
      small discrete clusters, males should show efficient mate searching more so than
      time-consuming 'handling' (e.g. fighting, mate persuasion). Natural history
      studies and computer and mathematical modelling generate this expectation. This
      long-term field study of prairie rattlesnakes in Wyoming indicated that straight
      line (i.e. fixed-bearing) movement by males is critical for mate location and,
      thus, for mating success. Males that searched along straight-line paths located
      and mated with more females than those having less straight movement paths.
      Fighting was observed rarely, and no relationship was found between males'
      success at mate location and body mass and/or snout-vent length. Thus a range of
      traits may mediate competition and mating success among male snakes.

PMID- 9268465
TI  - Protective association and breeding advantages of choughs nesting in lesser
      kestrel colonies
AB  - Some bird species may breed close to aggressive predators to reduce predation
      risk by more dangerous, generalist predators. We tested this protective nesting
      association hypothesis by studying solitary choughs, Pyrrhocorax
      pyrrhocoraxbreeding within or outside lesser kestrel, Falco naumannicolonies in
      northern Spain (1993-1994). We found 27 potential predators of choughs and
      kestrels and confirmed predation on adults and nests of both species by at least
      eight common predators. We experimentally assessed the defence investment of
      choughs and kestrels towards a stuffed eagle owl, Bubo buboin 19 buildings shared
      by both species. Lesser kestrels were more efficient at detecting the predator,
      and defended more vigorously than choughs. Choughs clearly selected for breeding
      buildings where lesser kestrel colonies were installed. Breeding success of these
      choughs was much higher than that of choughs breeding alone, because of a lower
      percentage of nest failure. Benefits to choughs probably accrued from both the
      'parasitism' of the kestrels' nest defence and the dilution of predation risk in
      the colonies. Since lesser kestrels do not prey on choughs, this could be a good
      example of protective nesting association in birds.

PMID- 9268466
TI  - Asymmetrical turning during spermatophore transfer in the male smooth newt
AB  - During mating, male smooth newts, Triturus vulgarisshowed a population bias for
      turning left during spermatophore transfer. This is the first demonstration of
      asymmetrical sexual behaviour in an amphibian population. An experiment with a
      perfect female model showed that it was due to male rather than female
      lateralization. Left turning bias decreased progressively as more spermatophores
      were deposited, and no significant bias was detectable by the third deposition.
      The hypothesis that this was due to neuromuscular fatigue was tested but not
      supported. Turning orientation had no influence on the probability of the female
      picking up the spermatophore in her cloaca. The left turning bias has not been
      found in the great crested newt, T. cristatus

PMID- 9268467
TI  - Effects of adult mortality risks on parasitoid foraging tactics
AB  - When searching on Scots pines, females of the aphid parasitoid Pauesia silvestris
      responded to differences in mortality risks, host distribution and host quality
      by changing foraging tactics. They foraged more successfully (i.e. they laid more
      eggs per unit time) on the pine aphid Cinara pini than on Cinara pineaTherefore,
      the former species was considered to be of higher quality. However, P. silvestris
      suffered from a high mortality (19.5%) from ant aggression when foraging for C.
      piniwhile mortality was zero on pines with C. pineaAll females that were killed
      were foraging on the bark, while females searching on needles were safe from ant
      attacks. When searching for C. pineaP. silvestris spent significantly more time
      on needles if the aphid colonies were ant-attended. On pines with C. piniin
      contrast, females spent more time on bark in ant-attended colonies. The high
      adult mortality risk on bark was counterbalanced by a significantly higher
      foraging success in ant-attended colonies.

PMID- 9268468
TI  - Grooming down the hierarchy: allogrooming in captive brown capuchin monkeys,
      Cebus apella
AB  - Observations of captive female brown capuchin monkeys in five groups revealed
      that grooming is primarily the occupation of dominant females at both the
      individual and dyadic levels. When categorized according to rank class, alpha
      females were the only class to perform significantly more grooming than they
      received. These results are inconsistent with reports on vervets, baboons and
      macaques, and suggest that grooming in capuchin monkeys may have different
      functions from those reported for cercopithecine primates. A dyadic analysis
      revealed, however, that grooming occurred more often between closely ranked
      females, similar to what is seen in several Old World monkey species. Therefore,
      some aspects of grooming in capuchins are similar to that seen in Old World
      monkeys, but the way they distribute grooming is different, which may prompt a re
      evaluation of current theories regarding the social function of allogrooming in
      non-human primates.

PMID- 9268469
TI  - Repeatability of female choice in the guppy: response to live and videotaped
      males
AB  - The degree to which females are consistent in their mate preferences has
      implications for studies of sexual selection. Because choice of females for
      particular males may be affected by temporal changes in male characteristics,
      consistency of mate preferences of individual females of Poecilia reticulata was
      studied by presenting them with the same male pairs in consecutive trials under
      three experimental procedures: live males behind clear glass, live males behind
      one-way glass and images of males on videotape. Although females did not
      habituate to males in any of the experiments, they spent significantly more time
      in proximity to males behind clear glass than in the video and one-way glass
      presentations. Females preferred the bright male over the pale one in the video
      and the clear glass presentations, but not in the one-way glass experiment.
      Repeatability of preferences by individual females for a male was high in the
      video and one-way glass presentations but low in the clear-glass experiment.
      Behavioural interactions with the male in the clear-glass experiment affected
      both the time that females spent viewing males as well as female visual
      preferences. Results indicate that the video playback is not only useful for
      detecting differences between female preferences for morphological traits of male
      guppies, but is also much more effective in detecting preferences than the other
      two techniques, because it eliminates temporal variation in male behaviour.

PMID- 9268470
TI  - Paternal investment and reproductive success in the California mouse, Peromyscus
      californicus
AB  - In species with biparental care, the degree of parental investment of each parent
      may be related to the size of the litter, the parental effort of the partner and
      the probability of future reproductive success with the same partner. These
      factors were examined in single females and mated pairs of Peromyscus
      californicus who were required to 'forage' for food by running in a wheel.
      Offspring survival and growth, parental behaviour, amount of food obtained by
      running in the wheel and inter-birth intervals between litters were recorded.
      Females alone were able to raise litters of two pups, but not four pups. Mated
      pairs were able to raise a litter of four pups. Litters of one or two pups reared
      with the mother alone grew as fast as pups reared with both parents. Single
      females that kept their pups alive had a mean inter-birth interval of 53 days;
      paired females had a mean inter-birth interval of 37 days. These results show the
      effect of male parental investment on reproductive success when parents must
      forage for food: the presence of the male resulted in four times as many pups
      reared over a 74-day period as a female could rear on her own.

PMID- 9268471
TI  - Use of visual cover by domestic fowl: a Venetian blind effect?
AB  - Cover is a structural feature of the environment that animals can use to conceal
      themselves from predators or conspecifics or to gain shelter from inclement
      weather. Cover may also form a physical barrier limiting movement. It was
      hypothesized that domestic fowl, Gallus gallus domesticuswould use visual cover
      for concealment. Use of cover was examined in two strains of domestic fowl kept
      indoors in four groups of 110-112 birds each. In each pen, cover was provided by
      four rigid vertical panels, one in each of four quadrants. Four similar quadrants
      were without cover. To investigate use of cover for concealment, the four cover
      structures varied in continuity of visual cover: (1) transparent (0% cover), (2)
      transparent with four equidistant vertical green stripes (33% cover), (3)
      transparent with eight such stripes (67% cover) and (4) solid green (100% cover).
      Scan samples of quadrant use were made weekly when the birds were 24-52 days of
      age. Both strains of domestic fowl (1) used areas with cover more than areas
      without cover, (2) showed increased resting and preening behaviour in areas with
      cover and (3) showed increased use of cover as continuity increased from 0 to
      67%. These results could not be explained by thermoregulatory or physical barrier
      effects of the cover structures. The results are consistent with the hypothesis
      that a preference for concealment motivates the use of visual cover by domestic
      fowl, and suggest a 'Venetian blind' effect for visually discontinuous security
      cover.

PMID- 9268472
TI  - Behavioural risk factors in the reproduction of inbred and outbred oldfield mice
AB  - The present study investigated two rarely measured aspects of inbreeding
      depression: the relationship between inbreeding and behaviour, and the
      possibility that inbred individuals that survive infancy may still suffer from
      inbreeding depression by failing to breed or failing to show appropriate mating
      or parental behaviours. Specifically, the relationship between (1) behaviour at
      pairing and reproductive success, (2) inbreeding and reproductive success and (3)
      inbreeding and pairing behaviour, was examined in two subspecies of the oldfield
      mouse, Peromyscus polionotusEffects of parental and offspring inbreeding were
      separated through experimental design and analysis. Activity level during the
      first 25 days after pairing predicted future reproductive success: pairs that
      remained less active during the nocturnal (active) period were significantly less
      likely to breed than pairs that remained more active. Inbred females took
      significantly longer to produce their first litters and were less likely to
      produce litters than were outbred females, independently of whether females were
      related to their mates (i.e. whether their offspring would be inbred). Inactive
      pairs averaged fewer surviving pups than did active pairs. Inbreeding coefficient
      of female was a significant predictor of activity level in one of the two
      subspecies, suggesting that inbreeding may affect behaviour. Inbred adult females
      showed inbreeding depression in the form of lower conception rates and fewer
      surviving offspring, although the specific traits affected differed for the two
      subspecies. The implications for captive breeding programs, and likely causes of
      the subspecific differences, are discussed.

PMID- 9268473
TI  - Reconciliatory grunts by dominant female baboons influence victims' behaviour
AB  - Following aggressive interactions, dominant female baboons, Papio cynocephalus
      ursinusoccasionally grunt to their victims. To examine the effect of these
      apparently reconciliatory grunts on victims' subsequent behaviour, a series of
      playback experiments was designed to mimic reconciliation. Victims were played
      their opponents' grunts in the minutes immediately following a fight and then
      observed for half an hour. After hearing these grunts, victims approached their
      former opponents and also tolerated their opponents' approaches at significantly
      higher rates than they did under control conditions. They were also supplanted by
      their opponents at significantly lower rates. By contrast, playbacks of control
      females' grunts did not influence victims' behaviour. Playbacks of reconciliatory
      grunts did not increase the rate at which opponents approached or initiated
      friendly interactions with their former victims. Playbacks of reconciliatory
      grunts, therefore, appeared to influence victims', but not opponents', perception
      of recent events.

PMID- 9268474
TI  - Size-assortative mating in Drosophila malerkotliana
AB  - The relationships between wing size, locomotor activity, mating latency,
      courtship pattern and mating success (total number of pairs mated in a given time
      unit) were studied in pairs of Drosophila malerkotlianaMating latency was
      negatively correlated with wing length and with locomotor activity while wing
      length and locomotor activity were positively related. In trios of a female and a
      long-winged and a short-winged male, long-winged males mated more successfully
      than short-winged males. In trios of a male and a long-winged and a short-winged
      female, long-winged males mated with long-winged females, and short-winged males
      with short-winged females. In addition, in pairs of long-winged/short-winged
      flies, long-winged flies courted and mated more successfully than short-winged
      flies.

PMID- 9268475
TI  - Effects of temporal and spatial variation in habitat quality on red squirrel
      dispersal behaviour
AB  - Immigration patterns and the frequency of breeding dispersal in tree squirrels
      are predicted to be related to the amount of temporal and spatial variation in
      tree seed crops, their primary food supply. We studied Eurasian red squirrel,
      Sciurus vulgarisdispersal patterns in a stable habitat with predictable food
      supply and a variable habitat with large temporal and spatial variations in food
      availability. In both habitats, we observed a male-biased immigration in spring
      and a female-biased immigration in autumn. However, there were more adults among
      immigrating red squirrels in the variable (66%) than the stable (31%) habitat and
      large differences in the extent of site fidelity between the two squirrel
      populations. Multivariate analyses indicate that food availability appeared to be
      the main factor affecting female dispersal behaviour. The data also suggest that
      female red squirrel dispersal patterns are an adaptive response to the
      predictability of food resources in space and time. Male dispersal behaviour
      seemed to be influenced by the distribution of the females. Their level of site
      fidelity was high in the stable habitat, whereas they appeared to track the
      movement of females in the variable habitat.

PMID- 9268476
TI  - A comparative study of virginity in fig wasps
AB  - In haplodiploid species, the presence of unmated (virgin) females that can
      produce only haploid male offspring may have several important effects on a range
      of phenomena such as reproductive strategies, the transmission of parasitic
      chromosomes and the evolution of eusociality. The strength of these effects will
      depend upon the prevalence of virgin females. Two theories make conflicting
      predictions concerning the importance of factors that should be associated with
      increased levels of virginity, emphasizing either the degree of local mate
      competition or brood size. In this paper, a model is presented which predicts
      that, under conditions of local mate competition, the prevalence of virginity
      should be negatively correlated with the average number of offspring developing
      in a patch. The different predictions were then tested using data from 53 species
      of fig wasps representing 15 genera from four continents. Across species, the
      estimated prevalence of virginity was significantly inversely related to brood
      size, but showed no correlation with sex ratio (an index of local mate
      competition), supporting the predictions of our model. Qualitatively similar
      results were found when a formal comparative analysis was carried out using a
      morphologically and molecularly based phylogeny.

PMID- 9268477
TI  - Red howling monkey use of specific defecation sites as a parasite avoidance
      strategy
AB  - Red howling monkeys, Alouatta seniculusin the central Amazonian basin move to
      specific sites before defecating. Differences in the vegetation profile of
      behavioural sites, defecation sites and random sites within the ranging area of
      howler groups were examined. The defecation sites used differed in the number of
      leaf intercepts at the levels of the forest the monkeys used for foraging and
      travelling. Defecating in areas free of underlying vegetation decreases the
      likelihood of contaminating potential food sources or arboreal pathways. This
      defecation behaviour may be an important parasite avoidance strategy of red
      howling monkeys.

PMID- 9268478
TI  - Song development by grey catbirds
AB  - What are the relative roles of imitation, improvisation and invention in the
      development of large song repertoires in species of the songbird family Mimidae?
      This question was addressed in a laboratory study of the vocal development of
      young grey catbirds, Dumetella carolinensiscollected from western Massachusetts.
      Two groups heard a repeated 10-s, tape-tutored segment of catbird song, two other
      groups heard a repeated 16-min segment and a fifth group heard no tape-tutored
      songs. One male selected for study from each group developed a large repertoire
      of seemingly normal songs, and wild males responded strongly to songs of the male
      that had heard no tape-tutored song. Relying little on precise imitation and
      largely on improvising or inventing, each male developed a highly unique
      repertoire. A geographical survey of catbird song revealed little to no evidence
      of song sharing or microgeographical variation, which is consistent with the idea
      that imitation plays a relatively minor role in song development. Perhaps
      simultaneous selection for large repertoires and reduced geographical variation
      has led to such an emphasis on song individuality and non-imitative developmental
      processes.

PMID- 9268480
TI  - Sex ratios are multiply determined: a reply to James
AB  - No abstract

PMID- 9268479
TI  - Sex ratio at birth in Norway rats: comment on Hornig & McClintock
AB  - No abstract

PMID- 9268481
TI  - How to minimize sample sizes while preserving statistical power
AB  - No abstract

PMID- 9268483
TI  - INTRODUCTION. Part 1: Connectionist Models of Lexical Processing

PMID- 9268482
TI  - The biological relevance of testing for perfect symmetry
AB  - No abstract

PMID- 9268484
TI  - Vertebrate and invertebrate gap junctions: a common molecular basis?

PMID- 9268485
TI  - Antiproliferative effect of illimaquinone on Leishmania mexicana.
AB  - Illimaquinone, a sponge metabolite that disrupts the Golgi complex in mammalian
      cells, stopped proliferation and induced morphological and ultrastructural
      changes in promastigotes of L. mexicana. Radioactive labeling of proteins
      demonstrates an increased excretion function and diminution of membrane acid
      phosphatase activity, due probably to the vesiculation of the Golgi complex and
      alteration of the cell protein sorting mechanism. The result indicated that
      illimaquinone could be useful for the study of intracellular traffic in
      Trypanosomatidae.

PMID- 9268486
TI  - Effects of dipeptides containing the amino acid, proline on the chemotaxis of
      Tetrahymena pyriformis. Evolutionary conclusions on the formation of hormone
      receptors and hormones.
AB  - Our investigations demonstrate that proline-containing dipeptides can provoke a
      chemosensory response from the unicellular Tetrahymena pyriformis. The
      chemotactic effects of the dipeptides have a close relationship with the side
      chain and the lipophilicity of the amino-terminal amino acid. Comparison of
      'mirror' variants of proline-containing dipeptides points to the fact that
      dipeptides with small side chain and non-polar character amino acids (Gly-Pro,
      Ala-Pro) are preferred on the amino-terminal end. In the case of amino acids with
      very variable side chains, small (Pro-Gly) and the large side chain and non-polar
      character amino acids (Pro-Leu, Pro-Phe) on the carboxyl-terminal end can induce
      significant chemotactic responses. With valine on any terminus the proline
      containing dipeptide induced a weak repellent effect.

PMID- 9268487
TI  - Influence of successive and combined ultraviolet A and B irradiations on matrix
      metalloelastases produced by human dermal fibroblasts in culture.
AB  - To study the cumulative influence of UV irradiations on skin matrix alterations,
      human skin fibroblasts were irradiated successively three-fold, at 24 h
      intervals, with UVA (3x5J/cm2), UVB (3x8mJ/cm2), UVA plus UVB (3x5J/cm2 and
      3x8mJ/cm2) and the levels of 92 kDa gelatinase (pro-MMP9), 72 kDa gelatinase (pro
      MMP2) and plasma-membrane elastase type protease were determined, following
      subsequent 24-h culture in 10% serum-containing medium. UV irradiations had only
      minor influence (1.4-fold increase for UVB) on secreted levels of pro-MMP2 and
      decreased the amount of plasma membrane elastase produced by cells. It did
      however, for UVA and UVB alone, induce a significant increase of 66 kDa activated
      MMP2 production: 2.5- and 1.7-fold respectively. Such enhancement was not
      observed when combined irradiations were administered. UV exposure possessed a
      much higher influence on pro-MMP9 secretion by dermal fibroblast enhancing enzyme
      levels by 2.5-, 6.5- and 5-fold for UVA, UVB and UVA+UVB, respectively.

PMID- 9268488
TI  - Cytokine- and neuropeptide-mediated differentiation in retinal pigment epithelial
      cells in vitro.
AB  - To determine the mechanism of growth and differentiation of retinal pigment
      epithelial (RPE) cells it is important to understand the pathogenesis of several
      retinal diseases. Recently it has been reported that several cytokines and
      neuropeptides regulate the growth of RPE cells. In this study, the role of
      cytokines and neuropeptides in melanin synthesis, which is one indication of the
      RPE cell differentiation, was examined using chick RPE cells in vitro IL-1beta,
      TNF-alpha, substance P, beta-endorphin and methionine-enkephalin stimulated the
      melanin synthesis of RPE cells in a dose-dependent manner. The most effective
      concentrations of these agents on RPE cell melanin synthesis were not the same as
      that for RPE cell proliferation. These results indicate that cytokines and
      neuropeptides play an important role not only for the growth but also for the
      differentiation of RPE cells.

PMID- 9268489
TI  - Pancreas of Aselli in some species of the shrews (Sorex araneusneomys fodiens) as
      an analogue of the bursa of Fabricius in birds.
AB  - No organ equivalent to the bursa of Fabricius in birds, which is responsible for
      the production of B cells, has been found in mammals thus far. It has been
      suggested that Peyer's patches and the appendix along with the bone marrow play
      this role. In this study, the gland of Aselli of shrews was examined, whose
      function has not yet been clarified. The results of the study of the gland of
      Aselli in common and water shrews suggest this gland to be the key lymphoid organ
      analogous to the bursa of Fabricius. However, unlike the bursa of Fabricius, the
      gland of Aselli seems to fulfil two functions. It not only produces B cells, but
      also is the site of their terminal differentiation into plasma cells.

PMID- 9268490
TI  - Intranuclear network of 3-5 nm and 8-10 nm fibers in EL-4 lymphoma cells.
AB  - While much evidence indicates a high degree of spatial organization in the
      nucleus, the underlying molecular structures that support it remain poorly
      characterized. By extracting with high concentrations of RNase A in a
      modification of the sequential extraction protocol of Penman, we have identified
      a novel intranuclear network in the mouse lymphoma cell line, EL-4. Micrographs
      of embedment-free sections of extracted cells reveal anastomosing filaments of
      two different diameters: 3-5 nm and 8-10 nm. The 3-5-nm filaments are
      interconnected in many junctions and appear to blend smoothly into each other.
      The 8-10-nm fibers frequently split into two 3-5-nm filaments. Some 3-5-nm fibers
      appear to be connected at 90 degrees angles with the 8-10-nm fibers. All
      junctions are smooth with no apparent junction protein. Flow cytometric analysis
      of RNase A- (and DNase I-) extracted nuclear matrices indicates that they do not
      contain significant amounts of protein that react with anti-actin and anti
      vimentin monoclonal antibodies. Extraction of EL-4 nuclear matrices with high
      salt does not reveal 8-10-nm core filaments described after similar treatment of
      tumor cell lines of cervical and mammary origin. The novel characteristics of the
      core filaments in EL-4 lymphoma cells may reflect cell-type specificity of the
      nuclear matrix.

PMID- 9268491
TI  - Changes of phosphatidylcholine-specific phospholipase C in hepatocarcinogenesis
      and in the proliferation and differentiation of rat liver cancer cells.
AB  - The biological significance of phosphatidylcholine-specific phospholipase C (PC
      PLC) in hepatocarcinogenesis and the proliferation and differentiation of rat
      liver cancer cells was investigated. The Ca2+-dependent activities of PC-PLC
      gradually increased during N-nitrosodiethylamine (DEN)-induced
      hepatocarcinogenesis and peaked at weeks 18-20 when the tumour formed. There was
      a close relationship between Ca2+-dependent PC-PLC activities and cellular DNA
      content, membranous gamma-glutamyltranspeptidase (gamma-GT), and tyrosine protein
      kinase. In contrast, Ca2+-independent PC-PLC activities decreased during
      hepatocarcinogenesis. Similarly, when CBRH-7919 rat liver cancer cells were
      treated with phorbol 12-myristate 13-acetate, a proliferation stimulator of the
      cells, gamma-GT and Ca2+-dependent activities of PC-PLC and the expression of
      alpha-fetoprotein increased significantly. However, when these cells were induced
      by retinoic acid to differentiate, Ca2+-dependent PC-PLC and gamma-GT activities
      decreased significantly, together with alpha-fetoprotein expression. There was a
      close relationship between Ca2+-dependent PC-PLC and gamma-GT activities during
      differentiation as there was during proliferation. We suppose that Ca2+-dependent
      PC-PLC is involved in rat hepatocarcinogenesis induced by DEN and that it plays
      an important role in the phorbol ester-induced proliferation or retinoic acid
      induced differentiation of liver cancer cells.

PMID- 9268492
TI  - Mapping of G2/M-phase prevalences of chaperon-encoding transcripts by means of a
      sensitive differential hybridization approach.
AB  - The sensitivity of the differential hybridization approach is significantly
      increased by the application of size-selected probes. RNA from elutriated phase
      synchronous Ehrlich ascites tumor (EAT) cells has previously been used to prepare
      cell cycle phase-specific cDNA libraries in the in-vitro transcription vector
      pBluescript. PCR amplification of the libraries with vector-fitting primer pairs
      generates amplified cDNA reflecting the mRNA complexities of cells in G1, S and
      G2/M phases. Probes with reduced complexities were recovered after side-by-side
      electrophoresis of equal amounts of PCR-amplified cDNA and elution of probes from
      parallel gel sections. Such size-selected probes release significant differential
      clones which escape their detection in the conventional differential
      hybridization approach. Three clones hybridizing preferentially with the G2/M
      phase-specific probe were further characterized. The genes were identified by
      their nucleotide sequences. They encode proteins known to be involved in protein
      folding: heatshock cognate protein, HSC 70; heatshock cognate protein, HSC 73;
      eta subunit of the chaperonin containing TCP-1 complex, CCT. The G2/M phase
      prevalent expression of these genes were further verified on the mRNA and on the
      protein level by Northern and Western blot analysis which confirms the
      significance of the differential hybridization approach and which indicates that
      the expression of this group of proteins increases with cell cycle progression.
      The expression of the chaperonin-containing TCP-1 complex appears to be
      specifically linked with the S to G2/M phase transition of the cell cycle.

PMID- 9268493
TI  - The preferential induction of a Th1 immune response by DNA-based immunization is
      mediated by the immunostimulatory effect of plasmid DNA.
AB  - In the present study, we have investigated the T cell response to the HBsAg,
      normally secreted as multivalent particles, and to beta-galactosidase, a
      cytoplasmic antigen, delivered as plasmid DNAs. We found that cytokines
      characteristic of a Th1 phenotype are produced in mice immunized by these plasmid
      DNAs. Using repeated injections of low doses of purified antigen, we demonstrated
      that neither prolonged presence of the antigen nor site of immunization resulted
      in an immune response with characteristics resembling those obtained with DNA
      mediated immunization. Analysis of immune responses induced in mice by
      coinjection of plasmid DNA and beta-galactosidase or HBsAg demonstrated that the
      coinjected DNA stimulated a Th1 response against the injected antigen. These data
      therefore strongly suggest that the strong immune response obtained after
      intramuscular DNA immunization was due to the adjuvant effect of the plasmid DNA
      which is also responsible for the selective activation of CD4(+) T cells with a
      Th1 phenotype.

PMID- 9268494
TI  - Allospecific cytotoxic T cells generated from beta 2m-/- mice in primary MLC:
      analysis of activation requirements, specificity, and phenotype.
AB  - It has been demonstrated by several investigators that beta 2m-/- knockout mice
      are deficient in the expression of MHC Class I molecules but can nevertheless
      generate CD8(+) allospecific cytotoxic T cells following vigorous in vivo
      priming. We demonstrate here that in vivo priming is not necessary to generate
      MHC Class I allospecific CTL from beta 2m-/- mice. When splenocytes from naive
      unprimed beta 2m-/- mice were provided exogenous cytokines in MHC Class I
      disparate primary MLC, allospecific cytolytic effectors were generated. beta 2m-/
      MHC Class I allospecific CTL that were CD3+ and Thy1.2+ were otherwise
      heterogeneous in phenotype, including CD8+, CD4+, CD8-CD4-, TCR alpha beta+, and
      TCR gamma delta+ T cells. This phenotypic variability of beta 2m-/- CTL generated
      in primary MLC reveals the diversity of CTL precursors that develop in vivo in
      the absence of MHC Class I.

PMID- 9268495
TI  - Retinoid regulation of interleukin-2 receptors on human T-cells.
AB  - The ability of retinoids to regulate interleukin-2 receptor (IL-2R) levels on
      human T-cells may play a fundamental role in the immunomodulating effects of
      these compounds. As a cell line model for studying this phenomenon, we tested the
      effects of retinoic acid (RA) on the expression of IL-2Ralpha and IL-2Rbeta in
      Hut78 cells, a mature T-cell line derived from a Sezary T-cell leukemia. Our
      results demonstrated 4- to 20-fold increases in the surface expression and mRNA
      levels of both of these receptor components at RA concentrations starting at 10(
      10) M with maximal induction at 1 microM RA. RA-induced upregulation of IL-2Rbeta
      was found to be transcriptionally mediated in a protein-synthesis-independent
      fashion; however, activation of the IL-2Rbeta promoter could not be demonstrated
      in transient transfection experiments utilizing reporter gene constructs
      containing all currently known regulatory elements of the IL-2Rbeta promoter.
      Enhancement of IL-2Ralpha/beta by RA was accompanied by upregulation of the
      expression of CD38, CD69, CD45RO, and HLA-DR, surface molecules known to be
      associated with T-cell activation. Parallel effects were induced by RA on T
      blasts generated from primary human lymphocytes suggesting the physiologic
      relevance of the Hut78 cell line model. Taken together, our findings demonstrate
      the ability of RA to upregulate IL-2R expression and enhance the activation state
      of Hut78 cells. The dramatic enhancing ability of RA on IL-2Rbeta expression does
      not appear to be mediated through interaction with currently defined regions of
      the IL-2Rbeta promoter.

PMID- 9268496
TI  - Altered response to and production of TGF-beta by B cells from autoimmune NZB
      mice.
AB  - New Zealand Black (NZB) mice spontaneously develop immune dysfunction manifested
      as autoimmune hemolytic anemia and systemic lupus erythematosus. In later life, a
      subset of these mice develop clonal CD5+ B cell tumors analogous to human chronic
      lymphocytic leukemia (CLL). NZB disease is marked by B cell hyperactivity
      characterized by spontaneous immunoglobulin secretion and proliferation.
      Elimination of autoreactive lymphocytes by apoptosis is a vital mechanism to
      prevent expansion of self-reactive lymphocyte population. TGF-beta appears to be
      an important factor in normal and abnormal immune regulation and this cytokine
      may play a role in the development of chronic human B cell tumors. We asked
      whether the response to or production of TGF-beta by NZB B cells was aberrant and
      could contribute to disease development. In this study, we demonstrated that the
      apoptotic response to TGF-beta was increased in B cells from NZB mice compared to
      B cells from normal BALB/c mice. The increased apoptosis was related to
      endogenous activation and was possibly mediated through increased expression of
      the TGF-beta Type II receptor. Despite functional differences between CD5
      negative B cells and CD5-positive B cells, TGF-beta induced apoptosis in both
      populations to a similar extent. NZB B cells also secrete increased active TGF
      beta compared to BALB/c B cells. We suggest that the aberrant secretion of active
      TGF-beta and the increased response to the apoptotic effects of TGF-beta by NZB B
      cells may play a role in the disease process of these mice, perhaps attempting to
      limit the autoimmune phenomena, but possibly also contributing to generalized
      immunosuppression. We also suggest that the CD5(+) tumors in the NZB mouse may
      not be a fully appropriate model of human CLL, since CLL B cells are abnormally
      resistant to the apoptotic effects of TGF-beta.

PMID- 9268497
TI  - Staphylococcal enterotoxin B induces arthritis in female DBA/1 mice but fails to
      induce activation of type II collagen-reactive lymphocytes.
AB  - It has been proposed that superantigens are involved in the pathogenesis of
      autoimmune diseases. To test the possibility of superantigens inducing arthritis
      in naive mice, V beta 8-reactive superantigen staphylococcal enterotoxin B (SEB)
      was injected into naive mice. We used female DBA/1 mice, because they were
      susceptible to collagen-induced arthritis (CIA), in which the pathogenic T cells
      were supposed to preferentially use limited V betas of T cell receptors including
      V beta 8. Mild monoarthritis developed in uninjected hindlimbs of mice
      administered with SEB in higher frequency (an average incidence of 24%) than the
      control phosphate-buffered saline-injected mice (4.2%). Autoimmune responses in
      mice administered with SEB were compared with those in mice developing CIA.
      However, activation of type II collagen (IIC)-reactive T cells was not detected
      in SEB-injected mice. Production of autoantibodies, anti-IIC antibody and
      rheumatoid factor was also undetected. Although exact mechanisms of pathogenesis
      of this arthritis remain to be known, V beta 8+ T cells were activated for a long
      period and the unresponsiveness of V beta 8+ T cells was not detected in this
      strain. From these results, we discuss the pathogenesis of arthritis induced by
      SEB and the possibility that superantigen may play a role in the induction of
      autoimmune diseases.

PMID- 9268498
TI  - Nonreplicating recombinant vaccinia virus encoding human B-7 molecules elicits
      effective costimulation of naive and memory CD4+ T lymphocytes in vitro.
AB  - We constructed recombinant vaccinia viruses (recVV) encoding the human T-cell
      costimulatory molecules B7-1 and B7-2. To abrogate the vaccinia virus
      transcription termination signal for early genes, the cDNA of B7-1 had to be
      modified by a T through C sense mutation at position 766. Upon infection with
      replication incompetent and noncytopathic recVV, several tumor cell lines as well
      as cultured human fibroblasts expressed the costimulatory molecules. All these
      cells were capable of providing effective costimulation for proliferation of
      resting CD4(+) T-cells after infection with recVV encoding B7 molecules. The
      costimulatory effect could be blocked with CTLA-4 IgG fusion protein, the soluble
      ligand for B7. RecVV-induced overexpression of B7 on syngeneic EBV-transformed
      lymphoblastoid B-cells was able to costimulate the proliferative response of
      CD4(+) memory cells against VV antigens. The possibility of easily engineering a
      variety of human cells using recVV encoding human B7 molecules holds implications
      for the future design of vaccination strategies.

PMID- 9268499
TI  - CD4+ T cells reactivated with superantigen are both more sensitive to FasL
      mediated killing and express a higher level of FasL.
AB  - Naive CD4(+) T cells proliferate strongly in response to superantigens such as
      staphylococcal enterotoxin B (SEB). When these cells are rested and challenged a
      second time, they undergo activation-induced cell death (AICD). Fas/FasL
      interactions have been shown to mediate AICD, even though the level of Fas
      expression in the 2 degrees SEB responder populations is no higher than in the 1
      degrees cultures. To determine whether the dissimilarity between the 1 degrees
      and 2 degrees cultures could be attributed to differences in FasL cytotoxic
      activity or in the sensitivity of the Fas apoptosis signaling pathway, we
      compared these parameters during the 1 degrees and 2 degrees responses of lpr and
      gld CD4+ T cells (which do not undergo AICD due to a lack of Fas and an inactive
      FasL, respectively) so that each parameter could be evaluated independently. The
      results demonstrate that 2 degrees responders both express a higher level of
      functional FasL and are more sensitive to FasL-mediated killing. These findings
      account for the differences between the 1 degrees and 2 degrees responses of CD4+
      T cells to superantigen. In addition, we found that the apparent level of FasL
      mediated cytotoxic activity in the 2 degrees lpr CD4+ T cell population is much
      higher than that of wild-type cells, suggesting that deficient Fas expression
      leads to inordinately high levels of FasL expression or subsaturation of FasL
      binding sites.

PMID- 9268500
TI  - In vivo mechanisms of acquired thymic tolerance.
AB  - Injection of antigen into the thymus of adult animals induces specific systemic
      tolerance, but the mechanisms of acquired thymic tolerance are not well
      understood. To investigate these mechanisms we used a model of intrathymic
      injection of ovalbumin (OVA) in BALB/c mice. We show an antigen-specific decrease
      in proliferative responses to OVA, as well as a significant decrease in antigen
      specific IL-2 secretion and IFN-gamma production by splenocytes and lymph node
      cells of tolerant mice. Addition of recombinant IL-2 in vitro reversed the defect
      in IFN-gamma production by cells from OVA-tolerized animals, but did not reverse
      the proliferation or IL-2 production defects. By using an adoptive transfer
      system, where a small population of OVA peptide-specific CD4+ TCR transgenic T
      cells are transferred into syngeneic normal recipients, we show an absence of
      peripheral antigen-dependent clonal expansion of transferred CD4+ TCR transgenic
      cells in tolerant mice in vivo. There was an increase in clonotype-positive T
      cells in the thymus after immunization, confirming that activated T cells
      circulate through the thymus. Furthermore, thymectomy after intrathymic injection
      abrogates the effect of acquired thymic tolerance and restores antigen-dependent
      clonal expansion in vivo. We conclude that intrathymic injection of antigen
      induces Th1 cell unresponsiveness and prevents the peripheral expansion of
      antigen-specific CD4(+) T cells in vivo. This is the first demonstration that in
      acquired thymic tolerance antigen-specific T cells circulate to the thymus where
      they may be anergized or ultimately deleted.

PMID- 9268501
TI  - FLT3 ligand induces the generation of functionally active dendritic cells in
      mice.
AB  - FLT3 ligand (FL) is a recently described hematopoietic growth factor that
      stimulates the proliferation and differentiation of hematopoietic progenitors. We
      have investigated the effect of FL on murine hematopoiesis and dendritic cell
      (DC) generation and accumulation in lymphoid tissues and liver in vivo and in
      vitro evaluating the morphologic, phenotypic, and functional characteristics of
      these DC. We have observed extramedullary hematopoiesis in the mouse spleen with
      all lineages of hematopoietic cells represented after the administration of FL.
      Injection of FL results in a time-dependent and reversible accumulation of DC in
      the spleen, bone marrow, lymph nodes, and liver. Both flow cytometry and
      immunohistochemistry revealed a significant accumulation of DC in these tissues.
      Results of mixed leukocyte reaction suggested that these cells, isolated from
      murine bone marrow or spleen, were active as antigen presenting cells.
      Furthermore, cultivation of splenic and marrow cells with GM-CSF and IL-4 gave
      rise to large numbers of functionally active mature DC. Thus, the results of this
      study suggest that FL is a promising growth factor that stimulates the generation
      of large number of DC and may be a useful cytokine for the immunotherapy of
      cancer.

PMID- 9268502
TI  - In vivo the environmental pollutants lead and mercury induce oligoclonal T cell
      responses skewed toward type-2 reactivities.
AB  - An oligoclonal utilization of Vbetas has been reported for pathogenesis of
      several autoimmune diseases, anti-tumorigenic activity, and superantigen
      regulation of thymic T cell development. Altered ratios of Th1 and Th2 cells also
      are observed in immunodysregulations, leading to impaired cell-mediated immunity
      with an increased incidence of infectious disease or cancer and/or aberrant
      immunity that could culminate with an autoimmune disease. Lead (Pb) and mercury
      (Hg) are known pollutants with immunodisrupting activities; Hg is known to cause
      autoimmune glomerulonephritis. Both metals are known to suppress host resistance
      to pathogens. To further evaluate the manner by which these metals cause in vivo
      immunomodulation, their in vivo effects on Vbeta expression were evaluated along
      with the Th1 and Th2 frequency. Exposure of BALB/c mice to PbCl2 or HgCl2 induced
      an oligoclonal response with increases of Vbeta 5+, Vbeta 7+, and Vbeta 13+ CD4+
      splenic, but not thymic, T cells. A significantly skewed frequency of Pb-induced
      splenic Th2 cells expressing Vbeta 7 or Vbeta 13 over Th1 cells was determined by
      limiting dilution analysis, but this Th2 predominance was not observed with CD4+
      T cells expressing Vbeta 8. DO11.10 transgenic mouse exposed to Pb and antigen
      also demonstrated a skewed type-2 response evidenced by significantly increased
      IgE levels, lowered IFN-gamma levels, and increased IgG1 and lowered IgG2a anti
      OVA levels. Even in the absence of specific T cell responses to a Pb-induced
      antigen, due to the restricted T cell specificity in the transgenic mouse model,
      Pb still was able to skew the response toward type-2 reactivity. However, this
      skewing occurred only in the presence of antigen. Therefore, the Pb-induced
      oligoclonal T cell response in BALB/c mice which must be initiated by self
      antigens and was predominately type-2 may be responsible for autoantibody
      production and the detrimental health effects associated with Pb exposure.

PMID- 9268503
TI  - Agrin-induced postsynaptic-like apparatus in skeletal muscle fibers in vivo.
AB  - We find that when extrajunctional regions of denervated soleus muscles in adult
      rats are transfected with cDNA encoding rat agrin isoform Y4Z8, which is normally
      secreted by motor neurons at adult neuromuscular junctions, the myofibers express
      and secrete the neural agrin. Muscle fibers in the vicinity of transfection form
      at their surface specialized areas having extracellular, plasma membrane, and
      cytoplasmic protein aggregates, narrow and deep plasma membrane infoldings, and
      an accumulation of myonuclei, all of which are characteristic of the postsynaptic
      apparatus at neuromuscular junctions. We conclude that at ectopic neuromuscular
      junctions that form in the extrajunctional region of denervated adult soleus
      muscles after implantation of a foreign nerve, a single neural-derived factor,
      agrin, is sufficient not only to cause protein aggregation in the early stages of
      postsynaptic apparatus formation, as predicted by the agrin hypothesis, but also
      to bring about changes in conformation of the muscle fiber surface and
      distribution of organelles which appear as the apparatus reaches maturity.

PMID- 9268504
TI  - gamma-AChR/epsilon-AChR switch at agrin-induced postsynaptic-like apparatus in
      skeletal muscle.
AB  - We transfected the extrajunctional region of denervated soleus muscles in adult
      rats with neural agrin cDNA to induce myofibers to form postsynaptic-like
      apparatus containing acetylcholine receptor (AChR) aggregates. By 1 week
      approximately 30% of the AChR aggregates contained a mixture of epsilon-AChRs and
      gamma-AChRs while approximately 70% had only gamma-AChRs. If the transfected
      muscles were reinnervated in the original junctional region, the postsynaptic
      like apparatus, despite the absence of apposed axon terminals, gradually came to
      have only epsilon-AChRs. We conclude that at the postsynaptic apparatus of
      ectopic neuromuscular junctions formed by a foreign nerve implanted into the
      extra-junctional region of denervated muscles, agrin secreted by the axon
      terminal plays a direct role in the gamma-AChR/epsilon-AChR switch that occurs as
      the apparatus reaches maturity. Our findings, together with results from other
      studies, indicate further that agrin and acetylcholine are the only nerve-derived
      factors required for this switch.

PMID- 9268505
TI  - Structural and functional characterization of the rat neurotrophin-4 gene.
AB  - Neurotrophin-4 (NT-4) is a member of the neurotrophin family of growth factors.
      To study the molecular mechanisms that govern NT-4 expression, we have cloned and
      characterized the rat genome region encoding NT-4. The rat NT-4 gene consists of
      three exons: two 5'-flanking noncoding exons and a coding exon. NT-4 mRNA
      transcription is controlled by two promoters flanking the noncoding exons.
      Alternative splicing of the second intron results in a NT-4 mRNA with a different
      open reading frame, encoding a shorter protein lacking pre-NT-4 sequence. A rat
      NT-4 gene fragment, containing all exons and introns in addition to 1.4 kb of the
      upstream genomic sequence, has been introduced into mice. This transgene enables
      partial recapitulation of the expression pattern of NT-4 mRNA and confers
      activity-dependent expression of the NT-4 mRNA in muscle.

PMID- 9268506
TI  - Overexpression of c-src and n-src in the developing Xenopus retina differentially
      impairs axonogenesis.
AB  - To compare the roles of the nonreceptor tyrosine kinase c-src and its neuronal
      splice form n-src in developing neurons, Xenopus retinal precursors were
      transfected in vivo with c-src, n-src, or constitutively active mutants.
      Axonogenesis of retinal ganglion cells was markedly impaired by the expression of
      constitutively active c-src and only mildly affected by the expression of
      constitutively active n-src. This differential phenotype could not be accounted
      for by raised levels of intracellular tyrosine phosphorylation alone because the
      average anti-phosphotyrosine staining intensity of retinal neurons expressing
      mutant n-src was almost twofold greater than that of neurons expressing mutant c
      src. The expression of either constitutively active isoform inhibited
      photoreceptor differentiation by 72% but did not influence other cell fates.
      These results suggest that c-src and n-src have both overlapping and distinct
      activities in differentiating retinal neurons.

PMID- 9268507
TI  - Axon tracts correlate with netrin-1a expression in the zebrafish embryo.
AB  - Netrins are secreted molecules that can attract or repel growth cones from a
      variety of organisms. In order to clarify the extent and scope of the effects of
      netrins for guiding growth cones, we have analyzed netrin-1a within the
      relatively simple and well-characterized nervous system of zebrafish embryos.
      netrin-1a is expressed in dynamic patterns that suggest that it guides the growth
      cones of a wide variety of neurons. The spatiotemporal relationship of netrin-1a
      expression and extending growth cones further suggests that netrins may act to
      delineate specific pathways and stimulate axonal outgrowth in addition to
      attracting and repelling growth cones. Furthermore, aberrant outgrowth by
      commissural growth cones in the spinal cords of floating head mutants, in which
      netrin-1a expression is altered, is consistent with an in vivo, chemoattractive
      action of netrin-1a. These data suggest that netrins act on many growth cones and
      influence their behavior in a variety of ways.

PMID- 9268509
TI  - Suspension Flocculation by Polyelectrolytes: Experimental Verification of a
      Developed Mathematical Model
AB  - Using experimental data of AgI sol and poly(2-methyl-5-vinylpyridine) chloride,
      we show that there is good agreement between the developed mathematical model of
      suspension flocculation by polyelectrolytes and the experimental data. The rate
      constants of bridging and nonbridging aggregation of particles and of floc
      breakup, as well as their ratios, have been determined. It has been shown that
      the role of the nonbridging mechanism, as compared with that of the bridging one,
      diminishes when molecular mass of polyelectrolyte increases from 1.4 x 10(5) to
      9.3 x 10(5).

PMID- 9268508
TI  - Lerk2 (ephrin-B1) is a collapsing factor for a subset of cortical growth cones
      and acts by a mechanism different from AL-1 (ephrin-A5).
AB  - The transmembrane (TM) subfamily of Eph ligands and their receptors have been
      implicated in axon pathfinding and in pattern formation during embryogenesis.
      These functions are thought to involve repulsive interactions but this has not
      been demonstrated directly. In this study we used a growth cone collapse assay to
      determine if the TM ligands Lerk2 and HtkL have repellant guidance activity. We
      show that Lerk2, but not HtkL, is a collapsing factor for a subset of embryonic
      cortical neurons. Analysis of the effects of Lerk2 on both the morphology and the
      cytoskeleton of cortical neurons suggests a mechanism of action different from
      that of AL-1, a GPI-linked Eph ligand having similar repellant activity.
      Treatment with Lerk2 disrupts the organization of both the actin cytoskeleton and
      the microtubules and induces the formation of swellings in the center of the
      growth cone and along the axon. Measurement of the relative F-actin
      concentrations in the neurites and soma indicated that F-actin levels in the
      neurites decrease while those in the soma increase, with the net F-actin content
      of the neuron remaining unchanged. In contrast, we show that prolonged treatment
      with AL-1 leads to a net loss of F-actin, consistent with the hypothesis that AL
      1 acts by perturbing actin polymerization. These results provide evidence that
      the ectodomain of Lerk2 functions as a repellant guidance cue and show that,
      despite overlapping specificities in vitro, the biological activities of related
      ligands are not necessarily overlapping. Further, TM and GPI-linked Eph ligands
      appear to exert repellant activity by different mechanisms, opening up the
      possibility that they may have different effects on growth cones in vivo.

PMID- 9268510
TI  - Structural Polymorphism in a Four-Component Nonionic Microemulsion
AB  - The Winsor IV microemulsion system composed of octaethylene glycol mono n
      dodecylether [C12(EO)8]/1-dodecane + n-pentanol (1:1 by weight)/water has been
      investigated at constant temperature using small angle X-ray scattering and
      electrical conductivity measurements. The results obtained are interpreted in
      terms of structural evolution of the molecular aggregates as a function of the
      stepwise addition of water or (oil + alcohol). The size and shape of a variety of
      microstructures are described: small, spherical micelles near the water corner
      and hexagonal and lamellar mesophases, which are oil- and alcohol-poor. Simple
      multishell models of these provide some insight into how dilution with water or
      swelling with (oil + alcohol) influences the overall symmetry of the aggregates,
      pentanol and dodecane partitioning, surfactant headgroup conformation, and the
      contribution of pentanol to oil solubilization. The previously identified "local"
      lamellar structure [O. Regev et al., Langmuir 12, 668 (1996)], which is a
      surfactant-rich and (oil + alcohol)-rich intermediate state between the W/O and
      O/W regions, is characterized here as a type of ordered, but highly obstructed,
      bicontinuous microemulsion.

PMID- 9268511
TI  - Light Scattering Study on the Effect of Polymer Composition on the Structural
      Properties of PEO-PPO-PEO Micelles
AB  - Micelle structural properties were determined for five poly(ethylene oxide)
      poly(propylene oxide)-poly(ethylene oxide) triblock copolymer solutions at
      25&deg;C by using light scattering techniques. Size distributions for the
      Pluronic series P103, P104, P105, F108, and P123 were found from dynamic light
      scattering. Aggregation numbers from both dynamic light scattering and static
      light scattering were determined, and the results are interpreted using
      fundamental hydrodynamic and statistical thermodynamic models. The trends in
      aggregation behavior are discussed in terms of the surfactant composition. For a
      fixed poly(propylene oxide) content, surfactants with a higher poly(ethylene
      oxide) content were found to be less aggregated. For a fixed poly(ethylene
      oxide)/poly(propylene oxide) ratio, surfactants with a higher molecular weight
      were more aggregated. These results are shown to be in agreement with previous
      self-consistent mean-field calculations for the same series of polymers and are
      compared with "star" and "brush" model predictions for the effect of
      poly(ethylene oxide) chain length on the thickness of the micelle corona.

PMID- 9268512
TI  - Organized Structure of Lithium Perfluorooctanesulfonate at the Graphite-Solution
      Interface
AB  - The structure of aggregates of lithium perfluorooctanesulfonate (LiFOS) adsorbed
      to the interface between graphite and aqueous solution have been measured. This
      fluorocarbon surfactant produces aggregates which are long ( approximately 100
      nm) and thin ( approximately 5 nm), and about one molecule ( approximately 1.3
      nm) deep. The aggregates lie in straight, parallel arrays on the surface with a
      characteristic repeat distance, or period, perpendicular to the long axis. As the
      bulk concentration of LiCl is increased, the period decreases, but as the bulk
      concentration of LiFOS is increased, the period increases. The decrease in period
      on addition of salt is similar to that observed for sodium dodecyl sulfate (SDS)
      and is explicable in terms of electrostatic forces. The increase in period on
      addition of surfactant is in sharp contrast to the behavior of SDS and may be due
      to a higher surfactant packing-parameter for LiFOS.

PMID- 9268513
TI  - Adsorption Dynamics of Native and Pentylated Bovine Serum Albumin at Air-Water
      Interfaces: Surface Concentration/ Surface Pressure Measurements
AB  - The dynamics of adsorption of bovine serum albumin (BSA) and its pentylated
      derivative (p-BSA) at the air-water interface was investigated through the
      measurements of surface pressure (Pi) and surface concentration (Gamma) via a
      radiotracer technique. The steady-state values of Gamma and Pi ranged from 0.8 to
      1.3 mg/m2 and from 10 to 17 mN/m, respectively, for bulk concentrations of 0.5 to
      10 ppm in sodium phosphate buffer at ambient temperature. The rate of increase as
      well as the steady state value of Gamma were smaller whereas the rate of increase
      as well as the steady state value of Pi were slightly larger for p-BSA, which has
      a surface hydrophobicity higher than that of BSA. The observed apparent time lag
      for Pi was more pronounced at lower bulk concentrations. At lower ionic strengths
      and at pH away from pI (the isoelectric point) of BSA, the rates of adsorption at
      longer times were lower, thus resulting in smaller steady-state values of Gamma.
      The Pi-Gamma relationship during adsorption dynamics differed from the surface
      equation of state obtained with the spread monolayer. The area per adsorbed
      protein molecule (A) during adsorption was smaller than that for spread
      monolayer, indicating that the protein molecule partially unfolds during
      adsorption. A for p-BSA was larger than that for BSA due to more unfolding of the
      p-BSA because of its lower conformational stability, as evidenced by the changes
      in the CD spectra of protein solution upon heating as well as a decrease in the
      phase transition temperature. The steady-state Pi-Gamma relationship agrees well
      with the isotherm obtained from the monolayer experiments, thus indicating that
      adsorbed BSA molecules unfold more or less completely after sufficiently long
      times (>20 h). A previously developed model (G. Narsimhan and F. Uraizee, 1992,
      Biotech. Prog. 8, 187) was modified to better account for the electrostatic
      energy barrier to adsorption by postulating that the charges are uniformly
      distributed in an adsorbed protein layer of finite thickness. The predictions of
      the new model agree better with the data for native and p-BSA than the previous
      model, especially at low ionic strengths.

PMID- 9268514
TI  - An Intersurface Stress Tensor
AB  - Distributed forces resulting from molecular interactions between macroscopic
      bodies are usually concentrated near surfaces. A new formulation has been
      developed that replaces these distributed body forces by effective surface
      tractions and is not limited by the geometrical restrictions of Derjaguin's
      approximation. It offers great computational simplification over the use of the
      body-force distribution. The body-force distribution is integrated and
      partitioned to various surface elements. The resulting expressions for surface
      traction involve a second-order tensor termed the intersurface stress tensor. It
      is a symmetric tensor defined for any body in terms of the intermolecular
      potential and the shape of the body. It acts much like the internal stress
      tensor; the surface traction vector on a surface introduced into its field is the
      inner product of the tensor and the surface normal. The new surface formulation
      reduces to Derjaguin's approximation for the case of a half-space with a plane
      surface. Properties of the new tensor are explored. Actual components are derived
      for several geometries.

PMID- 9268515
TI  - Adsorbability of 1,1,1,2-Tetrafluoromethane (HFC134a) onto Plasma-Treated
      Activated Carbon in CF4 and CCl4
AB  - The adsorbability of 1,1,1,2-tetrafluoroethane (HFC134a), which has been the
      CFC12 replacement, onto tetrafluoromethane and tetrachloromethane plasma-treated
      activated carbon (FT-ACs and CT-ACs) was investigated. It is proved that the
      fluorine and the chlorine, which were produced by plasma treatment, were
      introduced into the pores having radii greater 7.5 A and with less than 7.5 A by
      plasma treatment, respectively. The adsorption site of HFC134a onto activated
      carbon may change with the quantities of fluorine or chlorine on the surface of
      the activated carbon. The amount of HFC134a adsorbed per unit specific surface
      area of FT-ACs and CT-ACs slightly increased a little compared to the untreated
      activated carbon (U-AC). The amount of fluoride ion eluted before the adsorption
      of HFC134a from the FT-ACs increased with the increasing plasma treatment time.
      That after the adsorption of HFC134a from only the activated carbon with the
      shortest plasma treatment time decreased. The amount of chloride ion eluted
      before the adsorption of HFC134a from the CT-ACs increased after 15 min of plasma
      treatment, but decreased with 30 min of plasma treatment. The chloride ion amount
      from the CT-ACs decreased after the adsorption of HCF134a. These results could be
      explained by the Langmuir constants a and Ws, which represent the adsorption
      equilibrium constant and the saturated amount of HFC134a adsorbed, respectively.
      The ratio of fluorine and chlorine species, the adsorption type, the layer
      interstitial type, and the covalent type, is different based on the plasma
      treatment time. It is concluded that the amount of HFC134a adsorbed onto the FT
      ACs and CT-ACs did not depend upon the change of pore structure by the fluorine
      and chlorine.

PMID- 9268516
TI  - Addition of (Tri-)Block Copolymers to Phospholipid Vesicles: A Study of the
      Molecular Morphology and Structure by Using Hydrophobic Dye Molecules as Bilayer
      Probes
AB  - A dispersion of soybean lecithin in water leads to the formation of multilamellar
      vesicles (MLVs), which on sonication break down into small unilamellar vesicles
      of approximately 50 nm in diameter. The addition of polymeric molecules in the
      liposomal system is thought to provide the liposomes with a steric barrier. The
      molecules used were (tri-) block copolymers (Synperonics) containing a central
      hydrophobic part (polypropylene oxide) and two hydrophilic chains (polyethylene
      oxide). The aim of this work was to study whether it was possible to anchor deep
      inside the lipid bilayer the copolymer hydrophobic block. The exact localization
      of the copolymer molecules was investigated using a multiprobe technique. The
      full spectra of two hydrophobic dyes, namely Nile red (NIL) and Pinacyanol
      chloride (PCYN), were compared while solubilized inside the liposome bilayer. The
      sensitivity of their spectral characteristics to polarity and self-aggregation
      produced a monitor of the bilayer microenvironment. The more hydrophobic NIL
      proved an accurate polarity sensor of the bilayer microenvironment and the
      formation of PCYN dimers and nonabsorbing aggregates can be directly related to
      the local (bilayer) concentration of the dye and the volume available to the
      solubilized dye molecules. Shifts of the maximum absorbance (lambdamax) for both
      dyes showed that the bilayer environment was becoming more apolar with increasing
      copolymer concentration. The absorbance peak of PCYN due to dimer/aggregate
      formation increased at moderate copolymer concentrations, indicating that the
      polymer is incorporated inside the lipid bilayer.

PMID- 9268517
TI  - Synthetic Glycolipids Monolayer and Related Langmuir-Blodgett Films: Importance
      of the Amphipathic Balance
AB  - Synthetic glycolipids were chosen on account of their ability to form a monolayer
      at the air/water interface. The first (G1) is a 1,3-dialkyl glycerol constituted
      by two identical C11 hydrocarbon chains and a hydrophilic N-acetyl glucosamine in
      position 2. The saccharidic moiety was separated from the glycerol backbone by an
      ethylene glycol spacer. The second molecule (G2) has the same structure but
      without the spacer. The G1 isotherm is smooth and continuous. The G2 isotherm is
      characterized by an atypical discontinuity. The study of the compression mode,
      the temperature variations, and compression-decompression cycle experiments
      allowed the characterization of this discontinuity. It corresponds to a
      supersaturation in the monolayer; it is related to a low relaxation speed and it
      occurs just before the transition phase. On CaF2 surfaces, the G1 and G2
      monolayers were transferred but they were not firmly retained. Hydrophilic
      surfaces constituted by the carboxylic head groups of behenic acid LB films
      allowed the retention of the glycolipid layers. On such surfaces, only two G1
      layers could be transferred, whereas G2 Langmuir-Blodgett films were built up
      with an XY stacking. These results are discussed with respect to the amphipathic
      balance within the glycolipid molecules.

PMID- 9268518
TI  - Electrophoretic Motion of Two Spherical Particles with Thick Double Layers
AB  - The electrophoretic mobilities of two interacting spheres are calculated
      numerically for arbitrary values of the double-layer thickness. A general formula
      for the electrophoretic translational and angular velocities of N interacting
      particles is derived for low-zeta-potential conditions. The present calculation
      complements the well-studied case of thin double layers. The results are compared
      with recent reflection calculations and are used to compute the O(phi)
      contribution to the electrophoretic mobility of a suspension. Particle
      interactions can be significant for values of the scaled particle radius kappaa
      </= 10. At kappaa = 1 the O(phi) contribution can increase by a factor of 2-3
      over its thin-double-layer value. The precise values depend on the strength of
      the double-layer repulsions as determined by the particle size. Fluctuations in
      the electrophoretic velocity are also calculated but would appear to be limited
      to about 10% of the mean velocity. The reflection results to order R-6, where R
      is the particle separation, are in good agreement with the numerical results for
      the suspension mobility and fluctuations but higher order reflections produce
      worse results. Although the effects of pair interactions are noticeable, the
      major result is that pair interactions even for quite thick double layers are not
      large.

PMID- 9268519
TI  - Adsorption of Cationic Polyacrylamide onto Monodisperse Colloidal Silica from
      Aqueous Electrolyte Solutions
AB  - Adsorption of a low linear charge density cationic polyacrylamide (CPAM) onto
      monodisperse silica particles has been studied over a wide range of KCl
      concentration (10(-3)-1 M) and pH (4-9). In parallel the surface charge density
      of silica particles with and without adsorbed polyelectrolyte has been
      determined. The adsorbed amount (Gamma) as a function of electrolyte
      concentration (cs) exhibits a maximum at cs approximately 0.1 M. As pH increases
      from 4 to 6, Gamma increases and then either reaches a plateau (cs </= 0.1 M) or
      decreases (cs > 0.1 M). These features can be rationalized in terms of the
      interplay between the different factors that govern polyelectrolyte adsorption.
      The effect of polyelectrolyte adsorption on the surface charge density of silica
      is largest at low cs. It decreases with increase of the salt content and vanishes
      at cs > 0.1 M. This suggests that at electrolyte concentrations lower than 0.1 M,
      the polyelectrolyte plays a dominant in surface charge regulation. The ratio of
      the adsorbed polyelectrolyte charge to total surface charge is close to unity at
      high pH. It increases drastically with decreasing pH and increasing salt. A large
      overcompensation of the substrate charge by polyelectrolyte at these conditions
      is established in the present work.

PMID- 9268520
TI  - An Experimental Study of Contact Angle Hysteresis
AB  - Advancing and receding contact angles of four organic liquids and water were
      measured on a variety of polymer surfaces and silicon wafers using an inclinable
      plane. Contact angles varied widely from liquid to liquid and from surface to
      surface. Surface roughness was relatively unimportant. Instead, the contact
      angles seemed to be more closely tied to the chemical nature of the surfaces. In
      general, contact angles increased with the liquid surface tension and decreased
      with the surface tension of the solid. Several definitions were used to calculate
      contact angle hysteresis from the experimental data. Although hysteresis is
      usually considered an extensive property, we found that on a given surface a wide
      range of liquids gave a unique value of reduced hysteresis. Apparently, reduced
      hysteresis represents an intrinsic parameter describing liquid-solid
      interactions.

PMID- 9268521
TI  - Dipyridamole Interacts with the Polar Part of Cationic Reversed Micelles in
      Chloroform: 1H NMR and ESR Evidence
AB  - The interaction of dipyridamole (DIP) with reversed micelles (RM) of
      cetyltrimethylammonium chloride (CTAC) in CDCl3 at different water contents was
      studied. The position and T1 relaxation of the water peak upon addition of extra
      water revealed three concentration ranges of CTAC: <10 mM (impurity water is
      mainly dispersed in CDCl3), >50-100 mM (water mainly inside the RM), and
      intermediate range. The resonances of CTAC protons in the polar layer broadened
      and displaced by up to 0.07 ppm as a function of CTAC concentration and extra
      water. At 10 mM CTAC, the addition of 40 mM DIP shifted the head group signals to
      high field by about 0.1 ppm. At high and intermediate CTAC concentrations, four
      nitroxide spin probes, hydrophobic 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO),
      hydrophilic 4-amine-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPAMINE), and
      lipophilic 5- and 16-doxyl stearic acids (5- and 16-DSA), underwent partial
      immobilization. The rotational correlation time of TEMPAMINE (rather than TEMPO,
      5-, and 16-DSA) in RM moderately increased upon addition of 1.5-2.0 mM DIP. At an
      excess of CTAC, only one DIP peak at 3.88 ppm remained measurable, and its
      selective T1 fell from 0.34 to 0.12 s. The association constant for DIP and CTAC
      was between 10 and 35 M-1. Thus, DIP incorporates into the polar region of RM
      influencing packing and dynamics of surfactant head groups. In contrast, in
      aqueous CTAC micelles, the preferential localization of DIP substituents is
      inside the nonpolar micelle core, and the binding constant is two orders of
      magnitude above that for RM.

PMID- 9268522
TI  - Thiocyanato and Iodo Complexation of Cadmium(II) Ions in Micellar Solutions of a
      Nonionic Surfactant Triton X-100
AB  - Complexation of the cadmium(II) ion with thiocyanate and iodide ions have been
      studied by precise titration calorimetry in micellar solutions of a nonionic
      surfactant Triton X-100 containing 0.4 mol dm-3 NaClO4 as a constant ionic medium
      at 298 K. With regard to the Cd(II)-SCN- system, the formation of [Cd(NCS)]+ and
      [Cd(NCS)(SCN)] in aqueous solution and [Cd(NCN)2(SCN)]- in micelles was
      established, though the complexation in micelles is not extensive. With the
      Cd(II)-I- system, the formation of [CdI]+, [CdI3]-, and [CdI4]2- was established
      in aqueous solution together with the formation of [CdI2], [CdI3]-, and [CdI4]2-
      in micelles. It is revealed that the complexation in micelles is accompanied by
      relatively large and negative enthalpies, which is ascribed to the enthalpies of
      transfer of [CdI3]- and [CdI4]2- from aqueous solution to micelles. This suggests
      that a hydrophobic complex with no capacity to form strong hydrogen bonds in
      water is favored in micelles.

PMID- 9268523
TI  - Phase Transformation Behavior at Low Temperature in Hydrothermal Treatment of
      Stable and Unstable Titania Sol
AB  - Nanosize titania sol was prepared from titanium tetraisopropoxide (TTIP) and
      conditions for the formation of stable sol were identified. As the H+/TTIP mole
      ratio decreased and H2O/TTIP mole ratio increased, stable sol was likely to be
      formed. The size and crystallinity remained unchanged after hydrothermal
      treatment of the stable sol at between 160 and 240&deg;C. However, hydrothermal
      treatment of unstable sol produced rod-like particles and crystallinity of
      particles was changed from anatase to rutile. This difference in phase
      transformation at low hydrothermal treatment temperature was likely to be caused
      by the fact that stable sol remained to be stable even after hydrothermal
      treatment, while unstable sol had a tendency to be aggregated.

PMID- 9268524
TI  - Preparation and Characterization of Barium-Strontium Hydroxyapatites
AB  - Barium-strontium hydroxyapatite solid solutions with different molar ratio Ba/(Ba
      + Sr) were synthesized by a wet method and characterized by various means. The
      solid solution particles could be prepared at molar ratios ranging from 0 to 1;
      however, Ba2+ ions were more difficult to be incorporated into hydroxyapatite
      crystals compared to Sr2+ ions. With increasing Ba2+ content, the particles grew
      and finally turned into pure rod-shaped barium hydroxyapatite particles with a
      size of ca. 0.2 x 2 &mgr;m. The resulting particles were agglomerates consisted
      of primary fine particles except for strontium hydroxyapatite. The molar ratios
      (Ba + Sr)/P of all the particles were larger than the stoichiometric ratio of
      1.67, suggesting that CO32- ions, OH- ions, and/or H2O molecules substitute for
      PO43- ions in the crystal lattices. The amount of CO2 adsorbed irreversibly on
      the particles increased with increasing (Ba + Sr)/P except for strontium
      hydroxyapatite and fitted a curve with a minimum at a cation/P ratio of ca. 1.56
      as well as other HAPs.

PMID- 9268525
TI  - Novel Poly(vinyl ether) Block Copolymers: Adsorption from Aqueous Solutions on
      alpha-Fe2O3 (Hematite) and the Mechanism of Colloidal Stabilization
AB  - The adsorption of diblock copolymers containing different block length ratios of
      polyvinylmethyl ether (PVME) and poly (vinyloxy-4-butyric acid) (PVOBA) from
      aqueous solutions onto alpha-Fe2O3 (hematite) was compared with the adsorption of
      the PVOBA and PVME homopolymers. The effects on the colloidal stabilization in
      relation to the chemical composition of the polymers were evaluated. The pH was
      between 7.5 and 9 in all experiments. The PVME homopolymer hardly adsorbs on
      alpha-Fe2O3, while an adsorbed amount of 0.31 mg/m2 was found for PVOBA, which
      behaves as a polyelectrolyte at the pH values used. The adsorbed amount of the
      block copolymers increases with increasing PVME chain length up to 0.95 mg/m2.
      The high affinity character in the adsorption isotherm is lost above a certain
      length of the PVME chain in the block copolymer. The adsorbed layer thickness
      increases with the PVME chain length, while at the same time the chain density on
      the surface decreases. Adsorption of PVOBA causes a high absolute value of the
      zeta potential (|zeta|) of the alpha-Fe2O3 particles. The value of |zeta| drops
      with an increasing length of the PVME chain. The stability of alpha-Fe2O3
      dispersions stabilized with block copolymers with a short PVME chain is mainly
      due to electrical double-layer repulsion. Full steric stabilization is obtained
      with sufficiently long PVME chains in the block copolymer, making these
      dispersions insensitive to the salt concentration.

PMID- 9268526
TI  - Minimization of the Free Energy of Arbitrarily Curved Interfaces
AB  - The minimization of the free energy of a two-phase system with an interface of
      arbitrary curvature leads to an extremum (Laplace) condition containing the
      pressure difference, DeltaP, between the two sides of the interface. The
      expression for DeltaP is a function of the normal curvatures and of the resulting
      bending moments which are themselves functions of the normal curvatures, the
      mathematical form of which depends on the particular model for the interfacial
      bending energy that has been employed. On this basis, conclusions can be drawn
      about the equilibrium shape and curvatures of an interface, e.g., for
      bicontinuous microemulsions and vesicles. In addition, the pressure difference
      between the inside and the outside of surfactant-laden interfaces can be
      calculated. This pressure difference influences the work of formation of
      microemulsion droplets. A section devoted to the boundary conditions has also
      been included where in particular the case of a liquid meniscus attached to a
      cylindrically shaped solid surface is treated.

PMID- 9268527
TI  - Surface and Structural Properties of Novel Titanium Phosphates
AB  - Two novel fibrous framework titanium phosphates having a similar formula,
      Ti2O(PO4)2&middot;H2O, and a layered titanium phosphate,
      Ti2O3(H2PO4)2&middot;2H2O, were synthesized and their properties were
      characterized with physicochemical methods, such as elemental analysis,
      thermogravimetry, nitrogen adsorption, X-ray diffraction, and 31P solid-state
      NMR. Nitrogen adsorption isotherms were measured on synthesized titanium
      phosphates in order to characterize their surface and structural properties. The
      specific surface area and total pore volume of the titanium phosphates studied
      were determined. The low-pressure nitrogen adsorption isotherms were used to
      evaluate surface heterogeneity of the synthesized materials by employing an
      advanced numerical procedure based on the regularization method.

PMID- 9268528
TI  - Modifications in Classic Relationships Corresponding to Gas/Solid Physical
      Adsorption
AB  - Most of the classic gas/solid isotherm equations are inconsistent with the
      general rules of surface thermodynamics. The mean cause of this inconsistency is
      the fact that, according to the exact thermodynamic relationships, if any
      calculations or considerations are made, the excess amount adsorbed on the
      surface should be taken into account. On the contrary, the classic isotherm
      relationships are calculated with the absolute amount adsorbed, that is, they
      neglect the differences between the densities of the gas-phase and the adsorbed
      phase. This neglection leads to contradictions, especially at high equilibrium
      pressures when the classic equations calculate the total adsorption capacity by
      extrapolation of the equilibrium pressure to infinity. However, under the
      critical temperature (Tc) this extrapolation is a physical nonsense and there are
      some conditions at which this extrapolation above Tc is also irreal. All these
      problems can be solved if the classic isotherm equations are transformed to
      modified forms including a new parameter chi, which assures in every respect the
      thermodynamic consistency (correctness).

PMID- 9268529
TI  - Changes in Acidity of Fe-Pillared/Delaminated Smectites on Heat Treatment
AB  - Hydroxy-iron smectites were prepared using solutions with a OH/Fe content of
      about 1.2 and 2.5. To study thermal stability, the samples were heated in air at
      temperatures between 473 and 873 K. Changes in surface chemistry imposed by heat
      treatment were evaluated using potentiometric titration. The pKa distributions
      revealed peaks characteristic for iron complexes (FeIII) deposited on the surface
      of smectite. Heat treatment resulted in significant changes in the chemistry of
      the material and creation new species; however, the sorbents textural properties
      did not alter significantly. Data obtained from X-ray diffraction and sorption of
      nitrogen demonstrate that iron species are adsorbed mainly on the external
      surface of smectite and that the properties of the final products depend upon the
      OH/Fe ratio of hydroxy-iron solutions used in their preparation.

PMID- 9268530
TI  - The Surface Chemistry of Hybrid Nanometer-Sized Particles
AB  - Nanometer sized Au/TiO2 particles were synthesized by irradiation of a HAuCl4
      solution containing colloidal TiO2 with light of wavelength (lambda) >330 nm. The
      absorption maximum attributed to the surface plasmon band of gold was observed at
      530 nm, a red shift of about 10 nm from the position in aqueous solution. The
      particle size of Au/TiO2 determined by TEM was about 25 nm. The Au clusters are
      situated on the surface of TiO2 in terms of microcrystallite, which was confirmed
      by HRTEM, EDS, and XRD. A negative shift of binding energy in the Au 4f7/2 for
      gold cluster on the surface of TiO2 was found, and the electronic interaction
      between the metal and the support was discussed.

PMID- 9268531
TI  - Particle Structure and Stability of Colloidal Dispersions as Probed by the Kossel
      Diffraction Technique
AB  - A nondestructive Kossel diffraction technique based on the principle of back
      light scattering was used to characterize the structure formation which results
      from the interparticle interactions in colloidal dispersions. Static structure
      factors, radial distribution functions, and average pair potentials, which
      characterize the particle packing structures in model systems of hydroxylate
      latex dispersions, were obtained. The effects of particle concentration and
      polydispersity on particle structuring and dispersion stability were also
      studied. Computer simulations based on the Ornstein-Zernike method were compared
      with the experimental results. Good quantitative agreement was observed.

PMID- 9268532
TI  - Thermophoresis of a Small Evaporating Particle in a High-Temperature Diatomic Gas
AB  - Kinetic-theory analytical results are presented concerning the effect of intense
      evaporation on the thermophoretic force acting on a spherical particle suspended
      in a high-temperature diatomic gas for the case of free-molecule regime. Molecule
      dissociation and atom recombination are included in the analysis. It has been
      shown that evaporation may substantially enhance the thermophoretic force acting
      on a particle, especially for the case of the particle materials with low
      evaporation latent heat and small molecular weight and at high gas temperatures.
      The values of the effective atomic and molecular thermal-accommodation factors do
      not affect the thermophoretic force acting on a nonevaporating particle, but they
      affect significantly the evaporation-added thermophoretic force. It has been
      shown that the recombination fraction of atoms at the particle surface does not
      influence the thermophoresis.

PMID- 9268533
TI  - Surface Reactions of Apatite Dissolution
AB  - New experimental data about surface processes of interaction between natural
      apatite and phosphoric acid solutions were obtained by scanning electron
      microscopy, Auger electron spectroscopy, and IR reflection spectroscopy. The
      interaction was found to occur nonstoichiometrically (incongruently) on the very
      thin surface layer of apatite. The experimental data obtained were compared and
      extended with results taken from literature. The following sequence of ionic
      detachment from the surface of apatite to a solution was suggested: first
      fluorine for fluorapatite or hydroxyl for hydroxyapatite, next calcium, and
      afterward phosphate. A new chemical mechanism of apatite dissolution was proposed
      as a result. The mechanism for the first time described the surface irregularity
      of the dissolution process at the nanolevel. A comparison between this new
      dissolution mechanism and earlier mechanisms described in the literature was
      made.

PMID- 9268534
TI  - Synthesis of Uniform Ferric Oxide Particles from Deionized Colloids
AB  - A modified method was employed to prepare monodispersed colloidal particles of
      ferric (hydrous) oxide. The method contains three steps: (i) preparation of
      uniform nuclei of ferric hydrous oxide via a so-called instantaneous nucleation
      method; (ii) purification of the nuclei suspension via dialysis; (iii) aging of
      the purified nuclei suspension in a reflux reactor at certain pH. Cubic and
      pseudocubic alpha-Fe2O3 monodisperse particles which are much smaller than the
      cubic alpha-Fe2O3 particles obtained from the same reactant through a usual
      method were produced by aging needle like nuclei at a lower pH. A close-packed
      three-dimensional QDs (quantum dots) superlattice structure 40 nm in edge length
      with cubic geometry was formed by self-aggregation between spherical amorphous
      ferric hydrous oxide nuclei 3-5 nm in diameter. The growth processes of the two
      kind particles were also illustrated. This study showed an approach to prepare
      smaller particles from aqueous metal salt solutions in relatively higher
      concentration, and ordered QDs superlattice structure by controlled self
      aggregation of QDs in hydrosol.

PMID- 9268535
TI  - Solution Behavior of Anionic Surfactant Molecular Complexes
AB  - We have already reported the solution behavior as examined by electrical
      conductivity for cationic surfactant molecular complexes composed of quaternary
      ammonium salts such as CTAB and various aromatic additive species such as phenols
      and amines. By the same electrical conductivity method, we have obtained many
      valuable results which establish the newly obtained anionic surfactant molecular
      complexes to be novel surfactant species displaying their own characteristic CMCs
      and Krafft points different from those of their mother surfactants. Through the
      solution behavior, furthermore, we could deduce that a solubilized solution
      system that was of molar composition equal to that of the complex in the
      surfactant and the solubilizate (additive) was perfectly identical to the
      dissolution system of the complex. The facts satisfactorily confirmed that a
      solubilized solution system was only the dissolution system of the complex which
      spontaneously resulted in the process of solubilization.

PMID- 9268536
TI  - Asymptotics of a Pinhole
AB  - It is well known that, in a thin liquid film, corresponding to any particular
      thickness there is precisely one axisymmetric equilibrium solution to the Laplace
      Young capillary equation; i.e., corresponding to each film thickness there is a
      unique pinhole radius which has been shown to be unstable (1973, Taylor and
      Michael, J. Fluid Mech. 58, 625-639). We deduce an asymptotic relationship
      between film thickness and pinhole height in the limit of very thin films.

PMID- 9268537
TI  - Adsorption Isotherms of Bitumen/Aqueous Solutions of Intan-100
AB  - Adsorption isotherms for pure bitumen/aqueous solution of the non-ionic
      surfactant Intan-100 have been determined as a function of temperature using
      enhanced video pendant drop technique. The area/molecule occupied by the
      surfactant at the bitumen/water interface is about 3 times higher at 30&deg;C
      than at 60&deg;C at which maximum packing occurs. Isotherms for the model system
      heptane/aqueous solutions of Intan-100 indicate that maximum packing is not
      possible in the temperature range 20-60&deg;C. This fact implies that
      bitumen/water interface is a unique system where the natural surfactant present
      in the bitumen is playing a competitive role at the interface.

PMID- 9268538
TI  - Electron Microscopy of Modified Aluminum Alkoxide Microstructures on Freeze
      Drying
AB  - Direct imaging of microstructures in chelated aluminum alkoxide systems subjected
      to freeze-drying and freeze-thaw-drying is reported using cryo-scanning electron
      microscopy (SEM) and SEM techniques. Aluminum sec-butoxide was chelated with a
      beta-diketoester in different molar ratios. This system was gelled by hydrolysis
      under intense sonication. The sonogels formed were subjected to cryo-SEM. Samples
      for cryo-SEM were made by freezing the chelated alkoxide samples in liquid
      nitrogen and freeze-fracturing them inside the cryo-SEM and monitoring the
      apparent morphological changes on exposure to the cryo-SEM environment including
      intentional sample heating. Microstructures of unchelated, 1:1 chelated and 1:2
      chelated (alkoxide:chelate) sonogels after freezing, thawing, and drying were
      also imaged by SEM techniques. Heterogeneity introduced by chelation of alkoxide
      is proposed as the cause for the formation of flakes in freeze-thaw-dried
      chelated alkoxide gels. Microstructures of 1:1 chelated freeze dried alkoxide
      were compared with the freeze-thaw-dried gels. The absence of flakes in the
      chelated samples when subjected to in situ freeze-drying indicated reversible
      nature of the gels.

PMID- 9268539
TI  - Coalescence of Protein-Stabilized Emulsions in a High-Pressure Homogenizer
AB  - Coalescence rate constants in a high-pressure homogenizer were inferred for pure
      emulsions of a neutrally buoyant mixture of carbon tetrachloride and benzene
      dispersed in aqueous medium, as well as for emulsions stabilized by sodium
      caseinate or whey protein, from the temporal evolution of number of drops per
      unit volume in the exit stream of the homogenizer in a recirculating system
      consisting of the homogenizer and a stirred tank when subjected to a negative
      step change in applied homogenizer pressure (Ph). The homogenization pressure was
      varied in the range 6.9 to 41.4 MPa, pH in the range 5 to 7, dispersed phase
      fraction in the range 0.05 to 0.15, ionic strength in the range 0.01 to 0.05 M,
      and protein concentration in the range 0.01 to 0.05 wt%. Functional dependence of
      drop coalescence rate on the homogenizer pressure was derived for pure emulsions
      for mechanisms of drop collisions due both to turbulence and to shear. The
      inferred collision rate constant for pure emulsions was found to be proportional
      to Ph0.722, which was closer to the functional dependence for drop collisions due
      to turbulence. The coalescence rate constant was found to be higher for higher
      homogenizer pressures, larger drop sizes, and higher dispersed phase fractions.
      For emulsions stabilized by proteins, drop coalescence rate constant was found to
      be higher at lower protein concentrations, near the isoelectric point of the
      protein, and higher ionic strengths because of the smaller interdroplet colloidal
      repulsive forces, thus clearly demonstrating the effect of colloidal forces on
      drop coalescence. Sodium caseinate was found to result in a lower coalescence
      rate constant than whey protein.

PMID- 9268540
TI  - Rheological and Solid-Liquid Separation Properties of Bimodal Suspensions of
      Colloidal Gibbsite and Boehmite
AB  - Bimodal suspensions of nanometer-sized boehmite particles and micron-sized
      gibbsite particles in 0.10 M NaNO3 are used as models to gain insight into the
      physical properties of agglomerating colloidal suspensions containing bimodal
      distributions of primary particles. Results on the gibbsite-boehmite mixtures
      show that the presences of small particles in a suspension can have a dramatic
      impact on the rheological, sedimentation, and filtration characteristics of
      suspensions of larger particles. Transmission electron micrographs show that
      boehmite forms a coating on the larger gibbsite particles. The coating provides
      steric repulsion and reduces the attractive interactions between the larger
      particles, leading to viscosity decreases and greater densification of sediments
      and filter cakes. A model has been developed to rationalize observed property
      changes based on the range of agglomerate structures that can form in mixtures of
      large and small particles. Results are discussed in the content of the processing
      of nuclear waste sludges, but are applicable to a wide range of bimodal
      suspensions.

PMID- 9268541
TI  - Interfacial State Change of Cellulose Triacetate Membrane by Adsorption of
      Polyelectrolyte
AB  - Lysozyme, albumin, and PAS-H (poly diallyl dimethyl ammonium chloride), which are
      positively and negatively charged proteins, and cationic polysulfones,
      respectively, were adsorbed by a cellulose triacetate (CTA) membrane to
      investigate their effects on ionic transport through the membrane. The interface
      states between the membrane and the adsorption layer are discussed based on the
      measurements of contact angle and membrane potential and atomic force microscopy
      (AFM). The contact angle shows that the membrane changed from hydrophobic to
      hydrophilic due to adsorption of the above substances. AFM imaged the aggregates
      on the surface and showed that lysozyme, in particular, penetrates the membrane
      pores, making them shallower and decreasing their porosity. The results of
      membrane potential measurements showed that lysozyme and albumin did not change
      the membrane charge state, but PAS-H changed it from negative to positive. The
      permeability coefficients of KCl and K2HPO4 varied significantly with the
      adsorption of each polyelectrolyte. In particular, the permeability coefficient
      of phosphate through the lysozyme-adsorbed membrane increased to twice that of
      the nonadsorbed membrane. Such polyelectrolyte adsorption on the membrane surface
      can be used for the modification of commercial artificial kidney phosphate
      extraction.

PMID- 9268542
TI  - Determination of Association Constants for Cyclodextrin-Surfactant Inclusion
      Complexes: A Numerical Method Based on Surface Tension Measurements
AB  - Inclusion complexes of beta-cyclodextrin (beta-CD) with sodium octyl sulfonate
      (C8As), sodium dodecyl sulfonate (C12As), and sodium hexadecyl sulfonate (C16As)
      in aqueous solutions are studied by surface tension measurement at the air/water
      interface at different temperatures. At fixed concentrations of the surfactants,
      the surface tension increases with an increase in beta-CD concentration to a
      maximum value, at which it holds. The surface tension curves of the surfactants
      in the presence of beta-CD are higher than those in the absence of beta-CD. The
      curves rise higher with the increase in beta-CD concentration for each
      surfactant. The apparent critical micelle concentrations (CMC*) of the
      surfactants vary linearly with beta-CD concentration. The CMC* and surface
      tension values (including those after the CMC*) for the same system decrease with
      increase in temperature. A numerical method based on surface tension measurements
      is developed to determine the association constants for 1:1 inclusion complexes.
      This method is very reliable and easy to perform. The results demonstrate that
      the longer the hydrophobic tail of the surfactant, the greater the association
      constant with beta-CD, and that for the same surfactant the association constant
      is higher at lower temperatures.

PMID- 9268543
TI  - Adhesion between Oxide Nanoparticles: Influence of Surface Complexation
AB  - Colloidal cerium oxide particles of nanometer size are irreversibly adsorbed on
      molecularly smooth mica sheets from bulk dispersions. The approach to
      equilibrium, the homogeneity and stability of the adsorbed films, and the effects
      of pH and solution conditions, are determined by means of the surface force
      apparatus and atomic force microscopy techniques. Driven by electrostatic
      interactions between oppositely charged substrate and particles, a dense and
      relatively homogeneous flat film composed of ceria nanoparticles assembled in a
      single layer can be obtained. Coating substrates with nanometric particles gives
      a surface smooth at the nanometer scale only, but which is fully representative
      of a colloidal oxide/water interface. Force-distance profiles between such layers
      and colloidal stability can thus be compared. The long-range electrostatics
      repulsion is consistent with the zeta-potential values measured independently in
      bulk dispersions. An adhesion at contact between ceria is evidenced and its
      relation with the intricate colloidal stability of the oxide dispersions is
      demonstrated. The chemical origin for the adhesion between ceria surfaces is
      further supported by the effect that complexant molecules play. In their presence
      the ceria layers are protected and adhesion is prevented, with an efficiency
      increasing in the order nitrate < acetate < acetyl acetone. It appears that the
      stability of nanometric dispersions is better achieved by controlling the
      adhesion at contact rather than affecting the long-range electrostatic repulsion.

PMID- 9268544
TI  - NMR Self-Diffusion Studies of the Water and the Oil Components in a W/O/W
      Emulsion
AB  - The application of the pulsed field gradient NMR technique to a double emulsion
      is presented. This method determines the diffusion behavior of the different
      components of the emulsion. The details of the system studied, which is of the
      W/O/W type, have been taken from the literature. Information obtained pertains to
      the size distribution of the water droplets in both the starting emulsion and the
      double emulsion. In addition, the different phenomena that govern the oil
      diffusion in both systems have been identified and discussed.

PMID- 9268545
TI  - Synthesis, Surface Properties, and Hydrolysis of Chemodegradable Anionic
      Surfactants: Diastereomerically Pure cis- and trans-2,5-Disubstituted-1,3
      dioxanes
AB  - In our continuing systematic studies concerning the synthesis, surface
      properties, and hydrolysis of chemodegradable, diastereomerically pure surface
      active 2,5-disubstituted 1,3-dioxane derivatives, two new groups of anionic
      surfactants, sodium cis- and trans-(2-n-undecyl-1,3-dioxan-5-yl)methyl sulfates
      and sodium cis- and trans-3-[(2-n-undecyl-1,3-dioxan-5-yl)oxy]propanesulfonates,
      were synthesized and investigated. Surface properties of these surfactants, i.e.,
      surface excess concentration, Gamma, surface area demand per molecule, A,
      effectiveness of surface tension reduction, Pi, critical micelle concentration,
      CMC, and standard free energies of adsorption, DeltaGads0, and of micellization,
      DeltaGmic0, were determined. It was shown that the trans-isomers, in which the
      configuration of the polar group is equatorial, are more surface active than the
      cis-isomers with axial configuration of the polar group at the C-5 carbon atom of
      the 1,3-dioxane ring. The surfactants under study undergo easy hydrolysis
      reaction in DCl/D2O solution with cleavage of the 1,3-dioxane ring to nonsurface
      active intermediates. The trans-isomers are hydrolyzed faster than cis-isomers.

PMID- 9268546
TI  - Principal Component Analysis of the Absorption Spectra of the Dye Thiacyanine in
      the Presence of the Surfactant AOT: Precise Identification of the Dye-Surfactant
      Aggregates
AB  - Spectral change of a cationic dye 3,3'-diethylthiacyanine iodide (THIA) in the
      presence of an anionic surfactant AOT has been presented. The THIA-AOT system
      exhibits blue-shifted metachromasia at AOT concentrations below its critical
      micellar concentration (CMC) and is thought to be due to the aggregation of
      electrostatically bound dye-AOT complex (DS). Metachromasia is gradually reversed
      to the monomeric band (peak at 425 nm) by AOT above its CMC. Principal component
      analysis (PCA) method has been applied for spectral analysis; the results show
      that the metachromatic peaks at 377 and 366 nm originate, respectively, from
      trimer and hexamer of the dye associated with AOT. From PCA, the molar absorption
      coefficient spectra of the individual absorbing components and the equilibrium
      constants for the systems, monomer right harpoon over left harpoon trimer and
      hexamer right harpoon over left harpoon monomer below and above CMC of AOT,
      respectively, have also been obtained. The micellar aggregation number of AOT
      obtained from PCA is found to be 16 which is in good agreement with the
      literature value.

PMID- 9268547
TI  - Interaction of Cadmium with Phosphate on Goethite
AB  - Interactions between different ions are of importance in understanding chemical
      processes in natural systems. In this study simultaneous adsorption of phosphate
      and cadmium on goethite is studied in detail. The charge distribution (CD)
      multisite complexation (MUSIC) model has been successful in describing extended
      data sets of cadmium adsorption and phosphate adsorption on goethite. In this
      study, the parameters of this model for these two data sets were combined to
      describe a new data set of simultaneous adsorption of cadmium and phosphate on
      goethite. Attention is focused on the surface speciation of cadmium. With the
      extra information that can be obtained from the interaction experiments, the
      cadmium adsorption model is refined. For a perfect description of the data, the
      singly coordinated surface groups at the 110 face of goethite were assumed to
      form both monodentate and bidentate surface species with cadmium. The CD-MUSIC
      model is able to describe data sets of both simultaneous and single adsorption of
      cadmium and phosphate with the same parameters. The model calculations confirmed
      the idea that only singly coordinated surface groups are reactive for specific
      ion binding.

PMID- 9268548
TI  - Preparation and Properties of Uniform Coated Inorganic Colloidal Particles
AB  - Uniformly coated particles were obtained when dispersions of colloidal
      ellipsoidal hematite in manganese(II) 2,4-pentanedionate (MP), manganese(II)
      methoxide (MMO), and manganese sulfate/urea (MSU) solutions were aged under
      optimum experimental conditions. The shell formed in the hematite-MP system was
      amorphous, while those prepared with the other two manganese compounds were
      identified as crystalline MnO/MnO2 and MnCO3, respectively. On calcination at
      750&deg;C, amorphous and MnCO3 coatings converted to Mn2O3, whereas MnO/MnO2
      acquired only higher crystallinity without significant change in the
      morphological features of the particles. Electrophoretic measurements indicated
      that in all cases, shells significantly decreased the isoelectric point as
      compared to bare cores. The aging of the coating solutions of MP, MMO, and MSU in
      the absence of hematite resulted in uniform dispersed particles of Mn3O4/Mn2O3,
      MnO/MnO2, and MnCO3, respectively. On treating Mn3O4/Mn2O3 dispersions with a 30%
      solution of H2O2 for 72 h, partial oxidation to Mn2O3/MnO2 took place with
      simultaneous aggregation of the original particles to much larger spheres of
      narrow size distribution.

PMID- 9268549
TI  - Phosphate Adsorption on Hematite, Kaolinite, and Kaolinite-Hematite (k-h) Systems
      As Described by a Constant Capacitance Model
AB  - The constant capacitance model was used to describe phosphate adsorption on
      hematite, kaolinite, and a kaolinite-hematite system (k-h). The model assumes a
      ligand exchange mechanism and considers the charge on both adsorbate and
      adsorbent. The model is shown to provide a quantitative description of phosphate
      adsorption on these, including the effect of varying pH values. The computer
      program Ma-Za 2, a program that fits equilibrium constants to experimental data
      using an optimization technique, was used to obtain optimal values for the anion
      surface complexation constants on hematite, kaolinite, and a kaolinite-hematite
      system, while the PC program Ma-Za 1 in Q-Basic language was used for the
      application of the constant capacitance model. The model represented adsorption
      of phosphate anions well over the entire pH range studied (3.8-9.0). The main
      advantage of the model is its ability to represent changes in anion adsorption
      occurring with changes in pH. Extension of the model to describe phosphate
      adsorption in a mixed system, such as the kaolinite-hematite system, using the
      surface protonation-dissociation constant of hematite was qualitatively
      successful. In mixed system the model reproduced the shape of the adsorption
      isotherms well over the pH range 3.8-9.0. However, phosphate adsorption was
      overestimated. The hematite and the kaolinite-hematite system were synthesized
      and identified by X-ray, NMR, and FT-IR spectroscopy.

PMID- 9268550
TI  - Influence of Dynamic Surface Tension on the Spreading of Surfactant Solution
      Droplets Impacting onto a Low-Surface-Energy Solid Substrate
AB  - We have investigated the impact of single droplets of various surfactant
      solutions on a low-surface-energy solid substrate using a high-frequency
      visualization technique (one picture every 100 MUs). Whatever the surfactant, the
      drop spreads and retracts in about 1 s under the action of inertia and
      capillarity, respectively. During retraction, the capillary waves can be
      amplified and, in some cases, even yield droplet bouncing. Then, the droplet may
      slowly spread again due to gravity and the unbalanced capillary forces at the
      contact line between the droplet and the substrate. During the fast spreading
      process (2-3 ms), the droplet surface increases by almost one order of magnitude
      since its shape changes from a sphere to a flat pancake; this causes a strong
      deviation from thermodynamic equilibrium. The relevant surface property is
      therefore the dynamic surface tension which we have evaluated using a maximum
      bubble pressure apparatus. We have shown that droplet retraction is drastically
      influenced by the adsorption kinetics of the surfactant which limits the return
      to equilibrium surface tension.

PMID- 9268551
TI  - Concurrent Solution and Adsorption of Hydrocarbons in Gas Chromatographic Columns
      Packed with Different Loadings of 3-Methylsydnone on Chromosorb P
AB  - Thermodynamic properties of solution in 3-methylsydnone (3MS) and of adsorption
      at the nitrogen/3MS interface were gas chromatographically measured for a group
      of fifteen hydrocarbons at infinite dilution conditions. Retention volumes were
      measured at five temperatures within the range 37-52&deg;C in six columns
      containing different loadings of 3MS on Chromosorb P AW. Partition and adsorption
      coefficients were calculated and from their temperature dependence the
      corresponding enthalpies were obtained, although with considerable error;
      infinite dilution activity coefficients of the hydrocarbons in the bulk and in
      the surface phases demonstrated a strong correlation. Bulk activity coefficients
      in 3MS were very much smaller than those previously measured for the same solutes
      in formamide (FA) and in ethyleneglycol (EG), and were also smaller than what
      could be predicted on account of 3MS cohesive energy density as estimated from
      the quotient sigma/v1/3 (sigma, surface tension; v, molar volume). There was not
      such a large difference between the surface activity coefficients in the three
      solvents; furthermore, the quotients (surface activity coefficient/bulk activity
      coefficient) for a given solute in 3MS were twice as large as in FA and about
      three times larger than in EG. These results make evident the difficulties
      inherent in the prediction of surface phase properties from those in the bulk and
      cast doubts on the pertinency of employing the surface tension to compare
      cohesive energy densities of polar solvents with important chemical differences.

PMID- 9268552
TI  - Photopolymerization of Acrylate Films under an Imposed Spatial Irradiation:
      Thermodynamics of Relief Self-Development
AB  - UV irradiation through a lined mask of acrylate-based self-developing materials
      leads to the formation of a relief in the irradiated areas. Investigation of the
      effect of various properties, through a known two-layer model, showed the
      paramount importance of surface state on relief height. Both relief height and
      inhibition time of the growing kinetics are shown to be directly dependent on two
      surface properties: surface free energy and viscosity of the condensed state of
      the gaseous atmosphere adjoining the film.

PMID- 9268553
TI  - Preparation of Silica-Based Mesoporous Materials From Fluorosilicon Compounds:
      Gelation of H2SiF6 in Ammonia Surfactant Solution
AB  - The silica-based mesoporous molecular sieves were synthesized from fluorosilicon
      compounds and Al, Ti with the hydrolysis reaction of H2SiF6 in an ammonia
      surfactant mixed solution. Well-crystalline mesoporous molecular sieves were
      obtained after several hours at the atmospheric conditions. The solid products
      were characterized by X-ray powder diffraction, nitrogen adsorption/desorption,
      transmission electron microscopy and solid-state NMR spectroscopy. The solid
      products show high specific surface areas in the range of 627-1040 m2/g,
      depending on the amount of Al and Ti. Also, they exhibit narrow pore size
      distributions in the range of 31-35 A according to the addition of Al and Ti.
      29Si MAS NMR indicate that all samples mainly contain Q4 types sites. Also, the
      peak intensity of Q3 sites decreases with increasing amount of aluminum. In 27Al
      MAS NMR spectra, all samples give intense lines from 4-coordinate aluminum. These
      results show that aluminum species are incorporated into the framework of Si-MMS.
      As the amount of Al increases, the intensity line from 6-coordinate aluminum
      increases. This result represents the increase of the fraction of amorphous
      aluminum species.

PMID- 9268554
TI  - Tension and Compression of Electrorheological Fluid
AB  - Using the electrostatic polarization model and Hertzian contact theory, the
      tensile and compressive behaviors of dilute electrorheological fluids between two
      parallel electrodes are presented. It is shown that the load increases
      nonlinearly with decreasing distance of the two electrodes and is a linear
      function of the elastic modulus of dielectric particles. This qualitatively
      explains the rheopectic effect of electrorheological fluids under compressive
      loading.

PMID- 9268555
TI  - Aqueous Suspensions of Fumed Silica and Adsorption of Proteins
AB  - Thermally stimulated depolarization spectra of frozen aqueous suspensions of
      fumed silica show a dependence of relaxation processes on the concentration of
      silica (CSiO2) due to a change in the particle-particle interaction (their
      electrical double layers) and the concentration of bulk water (ice) with
      increasing CSiO2. A significant fraction of agglomerates of primary particle
      aggregates are not decomposed in aqueous suspensions of fumed silica. The
      thickness of an interfacial water layer perturbed by the silica surface or
      protein molecules was estimated from the dependence of 1H NMR signal intensity of
      unfrozen water on temperature below 273 K, separating the signals of water
      molecules weakly and strongly bound to the surface. Protein molecules adsorbed on
      fumed silica aggregates form hydrogen bonds with identical withSiOH or identical
      withSiO- groups by amino groups, e.g., H+NR from the zwitterion fragments.
      Aqueous suspensions of mechanochemically activated fumed silica do not lose
      protein adsorption ability during a long period in which the particles remain as
      microscaled agglomerates. According to AM1-SM1 calculations, complexes such as
      identical withSiO(H)&middot;&middot;&middot;H+NRCOO- are stabilized in aqueous
      suspensions of silica and the protein desorption rate decreases with increasing
      molecular weight of proteins.

PMID- 9268556
TI  - Desorption Behavior of Surfactant Mixtures at the Alumina-Water Interface
AB  - The desorption behavior of cationic-nonionic surfactant mixtures,
      tetradecyltrimethylammonium chloride (TTAC) and pentadecylethoxylated nonyl
      phenol (NP-15), at the alumina-water interface was studied. It has been found
      that while nonionic NP-15 itself does not adsorb at alumina-water interface, it
      will do so with cationic TTAC preadsorbed at the interface. During the desorption
      process, however, the presence of NP-15 in the system was discovered to cause
      desorption of TTAC. This is attributed to changes in equilibrium among surfactant
      monomers, mixed micelles, hemimicelles, and solloids upon the addition of NP-15:
      The cationic TTAC species at the interface is solubilized in NP-15 rich micelles
      in the bulk and perturb the equilibrium. This in turn is proposed to cause the
      desorption of NP-15 significant. The desorption behavior in the mixed surfactant
      system depends on the mixing ratio of surfactants in the mixtures. In nonionic NP
      15 rich mixtures, negative hysteresis is observed for the desorption of both TTAC
      and NP-15. In cationic TTAC rich mixtures, the effect of NP-15 on the desorption
      of TTAC is limited and the desorption of TTAC is similar to that in single TTAC
      system; in this case some positive hysteresis is observed for both TTAC and NP
      15.

PMID- 9268557
TI  - Reverse Micelle Formation of Triton X-100 in Butanol and n-Heptane Mixed Solvents
      Studied by the Positron Annihilation Technique
AB  - The positron annihilation technique (PAT) has been applied to study the molecular
      association phenomenon of Triton X-100 (TX-100) and formation of reversed
      micelles in the mixed solvent of butanol and n-heptane. The results indicate the
      sensitivity of positronium (Ps) parameters to the phase transition region due to
      the self-aggregation phenomenon of TX-100 within the system. The intensity of the
      long-lived ortho-Ps component, I3, and its lifetime, tau3, show a remarkable
      change at a critical concentration of the surfactant at approximately 1.5 mM
      coined as the operational CMC of TX-100 in both (1:1) and (1:2) butanol-n-heptane
      (BuHp) systems. The narrow component/para-Ps intensity as computed from Doppler
      broadening of annihilation radiation indicates discernable changes at the same
      concentration region ( approximately 1.5 mM) of TX-100 in the system. Further,
      microphase changes due to the association of water molecules within the
      nonaqueous phase has been studied by Ps parameters, which reveals a clear
      demarcation of the polar and nonpolar zones.

PMID- 9268558
TI  - Superlattice Formation on Star Polymer Solutions
AB  - Polyisoprene (PI) stars (arm number f = 4 approximately 237) were prepared by
      coupling of PI monoanions with tetrachlorosilane or by cross-linking PI anions
      with divinylbenzene. The structural ordering of such stars was investigated
      through small-angle X-ray scattering. PI stars (f > ca. 90) formed a body
      centered cubic (bcc) structure near the overlap threshold. This structure changed
      to a mixed lattice of bcc and face-centered cubic structures with increasing
      polymer concentration.

PMID- 9268559
TI  - Adsorption Kinetics of Ionic Surfactants with Detailed Account for the
      Electrostatic Interactions
AB  - The problem of diffusion-controlled adsorption from a non-micellar solution of an
      ionic surfactant in the absence of added electrolyte is solved analytically for
      the case of small deviations from equilibrium. For that purpose the electro
      diffusion equations of the transport of surfactant ions and counterions are
      combined with the Poisson-Boltzmann equation for the electrical field. The
      resulting set of equations is linearized and Laplace transform is applied.
      Analytical expression for the Laplace image of the adsorption is obtained in
      terms of elementary functions. Simple formulae for the short-time and long-time
      asymptotics of adsorption and surface tension relaxation are derived. To
      illustrate the effect of the electrostatic interactions we calculated the
      theoretical dependence of the characteristic relaxation time on the bulk
      surfactant concentration and surface potential for aqueous surfactant solutions
      in contact with various non-aqueous phases (air, heptane, decane, petroleum
      ether) and two surfactants: SDS and DTAB. The general trend is that the
      electrostatic effects decelerate the process of adsorption, as it could be
      expected. The derived exact analytical expressions quantifying these effects can
      be directly applied for the interpretation of experimental data for the kinetics
      of ionic surfactant adsorption. The reliability of our approach is verified
      through a comparison with other available theories.

PMID- 9268560
TI  - Gypsum Overgrowths Passivate Calcite to Acid Attack
AB  - The dissolution of calcite (CaCO3) in aqueous solution at pH below ca. 5-6 is
      known to proceed via the direct reaction of protons at the solid surface.
      However, exposure of the mineral to sulfuric acid is shown to lead to the rapid
      formation of an overlayer of calcium sulfate (gypsum) which completely passivates
      the surface against further reaction and dissolution. The overlayer is nucleated
      instantaneously on CaCO3 surfaces. Scanning electron and atomic force microscopy
      show that strongly adherent overgrowths are encouraged by a lattice matching
      between the cleavage (211) plane of calcite and the (010) plane of
      CaSO4&middot;2H2O.

PMID- 9268561
TI  - Standard Enthalpies of Adsorption of Di- and Trivalent Cations on Alumina
AB  - Standard enthalpies of Ni(II), Gd(III), and Y(III) adsorption on alumina can be
      estimated from the temperature effect on apparent equilibrium constants of
      surface reactions. The results are relatively insensitive to the choice of the
      adsorption model, although the calculated apparent equilibrium constants of
      surface reactions at a given temperature are model dependent and they often
      differ by several orders of magnitude from one model to another. The conditions
      of the experiment-solid-to-liquid ratio, initial concentration of multivalent
      cations in solution, presence of various 1:1 and 2:1 electrolytes at various
      concentrations-do not significantly affect the calculated values of standard
      enthalpies of adsorption. Assuming that the total number of surface sites and the
      number of protons released per one adsorbed heavy metal cation do not depend on
      temperature, the standard enthalpies of adsorption on alumina at constant pH are
      65 kJ/mol for Ni, 90 kJ/mol for Gd, and 90 kJ/mol for Y. The presence of alkaline
      earth metal cations (up to 0.05 mol dm-3) does not significantly influence the
      adsorption of nickel and gadolinium on alumina. Thus, barium and magnesium do not
      compete with heavy metal cations for the surface sites.

PMID- 9268562
TI  - Electrodynamic Trapping of Aerocolloidal Particles: Experimental and Theoretical
      Trapping Limits
AB  - Aerocolloidal particles have been trapped from an uncharged source aerosol using
      an electrodynamic balance. Graphite and soot particles were charged
      photoelectrically using a Xe2 (172 nm) excimer lamp, while particles of titanium
      dioxide, sodium nitrate, and diethylhexyl sebacate (DEHS) were charged using a
      unipolar corona charger prior to injection into the chamber. It was found that
      the Stokesian drag force produced by convection in the balance chamber can
      destabilize the levitated microparticle when it exceeds the electrostatic force
      required to center the particle. Although the electrostatic restoring force can
      be increased by increasing either the particle charge or the ac field strength,
      charging of the particles is more difficult as the particle diameter is
      decreased, which gives rise to a trapping limit. Monodisperse DEHS particles were
      used to determine the experimental trapping limit for unipolar charging. For the
      experimental apparatus used in this study, a diameter of about 1 MUm was found to
      be the trapping limit for DEHS. Results are compared to the theoretical trapping
      limit calculated by a force balance on a particle exposed to motion of the
      surrounding gas.

PMID- 9268563
TI  - Real-Time Monitoring of Peptide-Surface and Peptide-Antibody Interaction by Means
      of Reflectometry and Surface Plasmon Resonance
AB  - The performance of immunodiagnostic assays such as ELISA is governed by many
      different factors. Reflectometry was used to monitor peptide adsorption and the
      resulting antibody binding activity on a polystyrene surface. Surface plasmon
      resonance was used to analyze affinity and kinetic parameters of the
      (immobilized) peptide-antibody interaction. We demonstrate the capability of both
      the reflectometer and the BIAcore instrument to determine these immunoassay
      factors independently. When peptidic antigens other than the parent protein
      antigen were applied, reduced antibody binding activity (10 times lower) and
      faster dissociation (100 times faster) rather than poor adsorption proved to be
      the critical factors determining immune reactivity. When the peptides were
      modified chemically or when their molecular size was increased, antibody binding
      activity as well as affinity could be improved or even restored.

PMID- 9268564
TI  - Nitrogen Adsorption Studies of Novel Synthetic Active Carbons
AB  - Synthetic active carbons obtained via controlled carbonization of phenolic resins
      were characterized using low temperature nitrogen adsorption over a wide pressure
      range. It was shown that, although active carbons under study show appreciable
      differences in the BET specific surface area and the total pore volume, they
      exhibit quite similar porous properties. All samples were shown to possess a
      considerable amount of small micropores (ca. 0.7 nm). However, the active carbons
      have markedly different amounts of larger micropores (width above ca. 1 nm) and
      mesopores. It was shown that simple comparative methods, such as the high
      resolution alphas plot, provide valuable information about structural properties
      of active carbons. However, reliable adsorption data for suitable reference
      adsorbents need to be available in order to successfully apply the comparative
      methods. Therefore, a nitrogen adsorption isotherm was measured on a Cabot BP 280
      nongraphitized carbon black over a relative pressure range from 10(-6) to 0.99
      and the resulting data (104 points) are reported in a tabular form. In the high
      pressure region (relative pressure from 0.1 to 0.7), the isotherm for the BP 280
      sample exhibits a good agreement with the reference data available in the
      literature. Moreover, the adsorption isotherm currently reported covers the low
      pressure range, which is crucial in profound characterization of porous and
      nonporous solids by means of comparative methods of adsorption analysis.

PMID- 9268565
TI  - Contact Angles of Liquid Drops on Low-Energy Solid Surfaces
AB  - There have been many experiments that have determined the wetting behavior of
      liquids on low-energy solid surfaces. These experiments show that, in general,
      the contact angle, theta, measured through the liquid, increases with increasing
      liquid-vapor surface tension, sigmalv. Surprisingly, in experiments with some
      such surfaces, the contact angle of a drop appears to depend almost entirely on
      the liquid-vapor surface tension and very little on the other properties of the
      liquid. To gain some insight into this phenomenon, we have used a generalized van
      der Waals theory to model a diverse series of liquids on a low-energy substrate
      and to calculate the corresponding surface tensions and contact angles. We find
      that it is indeed possible to reproduce behavior similar to that seen in
      experiments, with the data for cos theta plotted versus sigmalv falling in a
      narrow band which could almost be interpreted as a smooth curve. The width of the
      band in our calculation depends on the ranges of the model parameters and on the
      details of the molecular interactions.

PMID- 9268566
TI  - Tryptophan, Tryptophan-Leucine, and BSA Adsorption at an Oil-Water Interface
AB  - Adsorption of the amino acid tryptophan, the peptide tryptophan-leucine and the
      protein bovine serum albumin (BSA) at buffered water-oleyl alcohol interfaces has
      been studied by ellipsometry. Tryptophan-leucine solutions showed a systematic
      change in ellipticity with concentration indicating an adsorption of 0.5 mg/m2
      for a solution concentration of 1 g/L and evidence of saturation at that
      concentration. BSA showed an adsorption of 0.45 mg/m2 for a concentration of 3.5
      g/L with no sign of saturation. There appeared to be little adsorption of
      tryptophan at the interface.

PMID- 9268567
TI  - Adsorption of DNA onto Polypyrrole-Silica Nanocomposites
AB  - DNA adsorption onto polypyrrole (PPy) powder, a colloidal silica sol, and three
      polypyrrole-silica nanocomposite particles (untreated and amine- or carboxylic
      acid-functionalized) was investigated at neutral pH using sodium phosphate
      buffer. The extent of DNA adsorption was found to be 32 and 22 mg/g for the
      aminated silica sol and aminated PPy-silica particles respectively, and 6.5 mg/g
      for the carboxylated particles. DNA adsorption onto the unfunctionalized PPy
      silica particles occurs to a lesser extent, whereas no adsorption was detected
      for the colloidal silica sol. Our results suggest that DNA adsorption is mainly
      governed by electrostatic and hydrophobic interactions. DNA is adsorbed onto
      polypyrrole chloride bulk powder and also onto the aminated PPy-silica particles,
      which both have cationic binding sites. The silica sol and the unfunctionalized
      PPy-silica particles both possess a net negative surface charge at this pH, which
      probably accounts for the zero or very low adsorbed amounts of DNA on these
      substrates. DNA adsorption onto the carboxylated PPy-silica particles may be
      enhanced by hydrogen bonding relative to the unfunctionalized polypyrrole-silica
      particles.

PMID- 9268568
TI  - Model systems for the study of kidney development: use of the pronephros in the
      analysis of organ induction and patterning.
AB  - Most vertebrate organs, once formed, continue to perform the function for which
      they were generated until the death of the organism. The kidney is a notable
      exception to this rule. Vertebrates, even those that do not undergo
      metamorphosis, utilize a progression of more complex kidneys as they grow and
      develop. This is presumably due to the changing conditions to which the organism
      must respond to retain what Homer Smith referred to as our physiological freedom.
      To quote, "Recognizing that we have the kind of blood we have because we have the
      kind of kidneys we have, we must acknowledge that our kidneys constitute the
      major foundation of our physiological freedom. Only because they work the way
      they do has it become possible for us to have bones, muscles, glands, and brains.
      Superficially, it might be said that the function of the kidneys is to make
      urine; but in a more considered view one can say that the kidneys make the stuff
      of philosophy itself" ("From Fish to Philosopher," Little, Brown and Co., Boston,
      1953). Different kidneys are used to make the stuff of philosophy at different
      stages of development depending on the age and needs of the organism, rather than
      the usual approach of simply making embryonic organs larger as the animal grows.
      Although evolution has provided the higher vertebrates with complex adult
      kidneys, they continue to utilize simple kidneys in embryogenesis. In lower
      vertebrates with simple adult kidneys, even more simple versions are used during
      early developmental stages. In this review the anatomy, development, and gene
      expression patterns of the embryonic kidney, the pronephros, will be described
      and compared to the more complex kidney forms. Despite some differences in
      anatomy, similar developmental pathways seem to be responsible for the induction
      and the response to induction in both evanescent and permanent kidney forms. Gene
      expression patterns can, therefore, be added to the morphological and functional
      data indicating that all forms of the kidney are closely related structures.
      Given the similarities between the development of simple and complex kidneys, the
      embryonic kidneys may be an ideal model system in which to investigate the
      genesis of multicomponent organ systems.

PMID- 9268569
TI  - Retinoic acid can block differentiation of the myocardium after heart
      specification.
AB  - While a number of transcription factors that are likely to play a role in cardiac
      differentiation have recently been described, the signals that lead to the
      expression of these factors remains poorly understood. Here we report that
      exposure of Xenopus embryos to continuous low levels of all-trans retinoic acid
      (RA), starting at the time of neural fold closure, blocks expression of
      myocardial differentiation markers. The development of the remainder of the
      embryo is relatively normal, suggesting that retinoic acid can act rather
      specifically on myocardial precursors. Indeed, the pattern of endocardial gene
      expression appears to remain unaffected by RA treatment. Although RA blocks
      myocardial gene expression, a superficially normal heart tube forms. The heart
      tube, however, fails to loop during subsequent development and never forms
      beating tissue. The effect of RA treatment on expression of myocardial genes is
      developmental stage dependent, since no influence is observed after myocardial
      differentiation has commenced. These data indicate that a vital component of the
      myocardial determination pathway is sensitive to retinoid signaling.

PMID- 9268570
TI  - Hensen's node provides an endogenous limb-forming signal.
AB  - Acquisition of limb-forming ability by discrete regions of the lateral plate of
      the chick embryo is thought to depend on a signaling cascade moving sequentially
      from the area of Hensen's node to the somitic mesoderm, the intermediate
      mesoderm, and then to the prospective limb-forming regions of the lateral plate
      (Stephens et al., 1991). In the present study it is demonstrated that grafts of
      Hensen's node can induce the formation of supernumerary rudimentary limbs from
      the non-limb-forming flank region of the lateral plate of stage 9-15 chick
      embryos. The rudimentary limbs that form from the flank in response to Hensen's
      node grafts often contain elongated, jointed cartilaginous elements arranged in
      three distinct proximodistal segments resembling the developing stylopod,
      zeugopod, and autopod and express the limb-characteristic genes Msx-2 and BMP-4.
      However, the rudimentary limbs are incomplete and nonpolarized in that they do
      not form girdles or paired skeletal elements and fail to express sonic hedgehog,
      FGF-4, and FGF-8, signaling molecules that have been implicated in regulating the
      patterning of the developing limb bud. These results indicate that Hensen's node
      can provide a limb-forming signal to the lateral mesoderm, but that other signals
      are necessary to promote the expression of genes required for the complete
      patterning and morphogenesis of the limb.

PMID- 9268571
TI  - Retinoic acid changes the proximodistal developmental competence and affinity of
      distal cells in the developing chick limb bud.
AB  - In the developing chick limb bud, retinoic acid (RA) has a striking effect on
      anteroposterior axis formation, resulting in a duplicated pattern of digits.
      There is no evidence, however, that RA affects proximodistal axis formation in
      the developing chick limb bud, although RA induces proximodistal duplication in
      regenerating amphibian limbs. We describe a series of investigations on the
      effect of RA on the proximodistal axis in the chick limb bud. A RA-containing
      bead applied to the anterior margin of the chick limb bud at stage 20 induces the
      anteroposterior duplication of autopodial structures at the wrist level. We found
      that the RA-treated tissue has the ability to form more proximal structures. When
      a tissue graft from the RA-treated anterior region was implanted into a stage 17
      wing bud (in which the stylopod is developing in the progress zone), the graft
      produced a humerus, radius-ulna, and digits. When the graft was implanted into a
      stage 19 wing bud (in which the zeugopod is developing in the progress zone), a
      zeugopod and digits were formed. These results were associated with changes in
      the expression of Hox-A genes in the RA-treated grafts, whose domains were
      reorganized to be similar to those in host tissues 24 h after grafting. When a
      small graft of RA-treated tissue was implanted into the apex of a stage 19 wing
      bud, the cells were found in the zeugopod and autopod, whereas cells of control
      fragments were found only in the autopod region. In vitro, distal cells from
      different stage limb buds are known to segregate from each other. However, RA
      treated stage 24 distal cells did not sort out from stage 20 distal cells and
      mixed homogeneously. These results suggest that RA induces distal cells to adopt
      "younger" properties which render them susceptible to forming more proximal
      patterns under the direction of host signals. The effects of RA on proximodistal
      patterns in developing chick limb buds appear to differ from its effects on
      proximodistal patterns in regenerating urodele limbs because RA can induce the
      proximodistal duplication in situ in the regenerating limbs.

PMID- 9268572
TI  - Haploinsufficient phenotypes in Bmp4 heterozygous null mice and modification by
      mutations in Gli3 and Alx4.
AB  - Bone morphogenetic protein 4 (Bmp4), a vertebrate homolog of Drosophila
      decapentaplegic (dpp), encodes a signaling protein with multiple functions during
      embryogenesis. Most mouse embryos homozygous for the Bmp4(tm1blh) null allele die
      around the time of gastrulation, with little or no mesoderm. Two independently
      derived Bmp4(tm1) mutations were backcrossed onto the C57BL/6 genetic background.
      Several independently expressed, incompletely penetrant abnormalities were
      observed in heterozygotes, including cystic kidney, craniofacial malformations,
      microphthalmia, and preaxial polydactyly of the right hindlimb. In addition,
      heterozygotes were consistently underrepresented at weaning. These results
      indicate that Bmp4 gene dosage is essential for the normal development of a
      variety of organs and for neonatal viability. Two mutations that enhance the
      penetrance and expressivity of the polydactylous phenotype were identified:
      Gli3(XtJ), a deletion mutation involving a gene encoding a zinc-finger protein
      related to Drosophila cubitus interruptus, and Alx4(tm1rwm), a targeted null
      mutation in a gene encoding a paired class homeoprotein related to Drosophila
      aristaless. All double Bmp4(tm1); Gli3(XtJ) heterozygotes have extensive anterior
      digit abnormalities of both fore- and hindlimbs, while all double Bmp4(tm1);
      Alx4(tm1) heterozygotes display ectopic anterior digits only on the hindlimbs.
      These genetic interactions suggest a model for the multigenic control of anterior
      digit patterning during vertebrate limb development.

PMID- 9268573
TI  - Chicken transcription factor AP-2: cloning, expression and its role in outgrowth
      of facial prominences and limb buds.
AB  - Embryonic facial development in chick embryos involves a sequential activation of
      genes that control differential growth and patterning of the beak. In the present
      study we isolate one such gene, the transcription factor, AP-2, that is known to
      be expressed in the face of mouse embryos. The protein sequence of chick AP
      2alpha is 94% homologous to human and mouse AP-2. Wholemount in situ
      hybridization with a probe for chick AP-2 identifies expression from primitive
      streak stages up to stage 28. The most striking expression patterns in the head
      are during neural crest cell migration when AP-2 transcripts follow closely the
      tracts previously mapped for neural crest cells. Later, expression in the facial
      mesenchyme is strongest in the frontonasal mass and lateral nasal prominences and
      is downregulated in the maxillary and mandibular prominences. Once limb buds are
      visible, high expression is seen in the distal mesenchyme but not in the apical
      ectodermal ridge. The expression patterns of AP-2 in stage 20 embryos suggested
      that the gene may be important in "budding out" of facial prominences and limb
      buds. We implanted beads soaked in retinoic acid in the right nasal pit of stage
      20 embryos resulting in a specific inhibition of outgrowth of the frontonasal
      mass and lateral nasal prominences. AP-2 expression was completely down-regulated
      in the lateral nasal within 8 hr of bead application. In addition, the normal up
      regulation of AP-2 in the frontonasal mass did not occur following retinoic-acid
      treatment. There was an increase in programmed cell death around the right nasal
      pit that accompanied the down-regulation of AP-2. Prominences whose morphogenesis
      were not affected by retinoic acid did not have altered expression patterns. We
      removed the apical ectodermal ridge in stage 20 limb buds and found that AP-2
      expression was partially downregulated 4 hr following ridge removal and
      completely downregulated 8 hr following stripping. Application of an FGF-4 soaked
      bead to the apex of the limb bud maintained AP-2 expression. Thus AP-2 is
      involved in outgrowth and could be regulated by factors such as FGFs that are
      present in the ectoderm of both the face and limb.

PMID- 9268574
TI  - Continuous observation of multipotential retinal progenitor cells in clonal
      density culture.
AB  - All neural cell types in the vertebrate retina, except astrocytes, have been
      shown to develop from multipotential progenitor cells. It is not known, however,
      to what extent the progenitor cells are heterogeneous in their developmental
      potential or to what extent cell-cell interactions versus cell-autonomous factors
      influence the types of cells they become. To address these issues we developed a
      clonal-density cell culture system where mouse retinal progenitor cells can
      survive, divide, and differentiate. We followed the development of clones both by
      continuous time-lapse video microscopy and by daily microscopic observation. We
      show that even when cultured at clonal density in a homogeneous general
      environment, where they cannot contact cells outside their own clone, the retinal
      progenitor cells vary in proliferative capacity, cell cycle time, and in the cell
      types that they generate. In addition, we show that under these conditions single
      progenitor cells can generate both neurons and glia, in which case the neurons
      almost always develop before glial cells, as is the case in vivo.

PMID- 9268575
TI  - Persistent expression of MNF identifies myogenic stem cells in postnatal muscles.
AB  - Skeletal muscles contain an undifferentiated myogenic stem cell pool (satellite
      cells) that can be mobilized to regenerate myofibers in response to injury. We
      have determined that the winged helix transcription factor MNF is expressed
      selectively in quiescent satellite cells, which do not express known regulators
      of the myogenic program. Following muscle injury, MNF is present transiently in
      proliferating satellite cells and in centralized nuclei of regenerating
      myofibers, but expression declines as these fibers mature, until only the
      residual stem cell pool continues to express detectable levels of MNF. MNF also
      is expressed selectively but transiently at embryonic stages of myogenesis in the
      developing myotome, limb bud precursors, and heart tube, but by late fetal stages
      of development, MNF is down-regulated within differentiated cardiac and skeletal
      myocytes, and persistently high expression is observed only in satellite cells.
      These data identify MNF as a marker of quiescent satellite cells and suggest that
      downstream genes controlled by MNF serve to modulate proliferative growth or
      differentiation in this unique cell population.

PMID- 9268576
TI  - Chicken Nkx-2.8: a novel homeobox gene expressed in early heart progenitor cells
      and pharyngeal pouch-2 and -3 endoderm.
AB  - Members of the NK family of homeobox transcription factors regulate critical
      steps of organogenesis during vertebrate development. In the studies described in
      this report, we have isolated and functionally characterized the chicken Nkx-2.8
      (cNkx-2.8) cDNA and protein and defined the temporal and spatial pattern of cNkx
      2.8 gene expression during chicken development. cNkx-2.8 transcripts are first
      detectable at HH stage 7 in the splanchnopleura. At stage 10(+), the cNkx-2.8
      gene is expressed in the linear heart tube and the dorsal half of the vitelline
      vein. However, after looping, HH stage 13, cNkx-2.8 is no longer expressed in the
      looped heart tube, but is expressed in the ventral pharyngeal endoderm. At stage
      15, in addition to the pharyngeal expression pattern, cNkx-2.8 is expressed in
      the ectoderm of the pharyngeal arches and the aortic sac. By HH Stage 17, cNkx
      2.8 expression is detectable in lateral endoderm of the second and third
      pharyngeal pouches, the posterior portion of the aortic sac, and the sinus
      venosus. cNkx-2.8 binds to previously characterized Nkx2-1 and Nkx2-5 DNA-binding
      sites and overexpression of cNkx-2.8 transactivates a minimal promoter which
      contains multimerized Nkx-2 DNA-binding sites. In addition, cNkx-2.8 and serum
      response factor can coactivate a minimal cardiac alpha-actin promoter. These data
      are consistent with a model in which cNkx-2.8 performs a unique temporally and
      spatially restricted function in the developing embryonic heart and pharyngeal
      region. Moreover, the coexpression of cNkx-2.5 and -2.8 raises the possibility
      that cNkx-2. 8 may have a redundant role with cNkx-2.5 in the coalescing heart
      tube and may play an important role in the transcriptional program(s) that
      underlies thymus formation. The existence of multiple NK-2 family members and
      their partially overlapping patterns of expression are discussed within the
      framework of a "Nkx code."

PMID- 9268577
TI  - A role for cyclin E/Cdk2 in the timing of the midblastula transition in Xenopus
      embryos.
AB  - During Xenopus development, the early cell cycles consist of rapid oscillations
      between DNA synthesis and mitosis until completion of the 12th mitotic division.
      Then the cycle lengthens and becomes asynchronous, zygotic transcription begins,
      and G phases are established, a period known as the midblastula transition (MBT).
      Some aspects of the MBT, such as zygotic transcription, depend on acquisition of
      a threshold nuclear to cytoplasmic (N/C) ratio, whereas others, such as maternal
      cyclin E degradation, are independent of nuclear events and appear to be
      controlled by an autonomous maternal timer. To investigate the function of cyclin
      E during the early cycles, cyclin E/Cdk2 kinase activity was specifically
      inhibited in fertilized eggs by a truncated form of the Xenopus Cdk inhibitor,
      Xic1 (Delta34Xic1). Delta34Xic1 caused lengthening of the embryonic cell cycles
      that correlated with increased levels of mitotic cyclins. However, DNA synthesis
      was not inhibited. Several hallmarks of the MBT were delayed for several hours in
      Delta34Xic1-injected embryos, including the disappearance of cyclins E and A, the
      initiation of zygotic transcription, and the reappearance of phosphotyrosine on
      Cdc2. In both control and Delta34Xic1-injected embryos, cyclin E was degraded
      after the 12th mitotic division as zygotic transcription began, but experiments
      with alpha-amanitin show that cyclin E degradation is not dependent on zygotic
      transcription. Thus, the length of the early cycles and the timing of maternal
      cyclin degradation depend upon cyclin E/Cdk2 activity. Neither oscillations in
      cyclin E/Cdk2 activity during the early cycles nor the disappearance of cyclin E
      at the MBT were dependent on protein synthesis. These data suggest that cyclin
      E/Cdk2 is directly linked to an autonomous maternal timer that drives the early
      embryonic cell cycles until the MBT.

PMID- 9268578
TI  - Genes induced in programmed cell death of neuronal PC12 cells and developing
      sympathetic neurons in vivo.
AB  - To identify primary response genes induced during early stages of neuronal
      programmed cell death (PCD), we screened by differential hybridization a
      subtracted cDNA library prepared from neuronal PC12 cells deprived of NGF for 6
      hr in the presence of cycloheximide. Eight induced cDNA sequences were identified
      and designated message up-regulated during death (mud)-1-8. To determine which
      cloned sequences might be involved in neuronal PCD in vivo, expression of mud
      genes was analyzed in developing rat superior cervical ganglia (SCG) undergoing
      programmed cell death, using a combination of reverse Southern, reverse
      transcription polymerase chain reaction (RT-PCR), and in situ hybridization. Five
      sequences (mud-1, -3, -5/8, -6, and -7) are induced in SCG undergoing cell death
      in vivo, and induction of at least three of these (mud-3, -6, and -7) occurs in
      neurons. Partial sequence analysis reveals that mud-1 corresponds to annexin VI;
      mud-3 corresponds to rat PC3, mouse TIS21; mud-4 appears to be the rat homolog of
      human TAFII70; mud-5 and -8 are >85% identical members of the rodent gene family
      of B2-transcribed repeats; and mud-6 appears to be the rat homolog of human Ring
      3 and Drosophila female sterile homeotic (fsh). Mud-2 and mud-7 encode novel
      sequences. These new candidate genes provide markers for early stages of neuronal
      PCD, are potentially involved in the cell death process, and serve to expand our
      view of cell death control in the developing nervous system.

PMID- 9268579
TI  - Evidence for the involvement of the Gli gene family in embryonic mouse lung
      development.
AB  - Murine Gli, Gli2, and Gli3 are zinc finger genes related to Drosophila cubitus
      interuptus, a component of the hedgehog signal transduction pathway. In the
      embryonic lung, all three Gli genes are strongly expressed at the pseudoglandular
      stage, in distinct but overlapping domains of the mesoderm. Expression of Gli and
      Gli3, but not of Gli2, is subsequently downregulated at the canalicular stage,
      coincident with a decline in the expression of sonic hedgehog (Shh) and the
      hedgehog receptor gene, patched (Ptc). Overexpression of Shh in the lung results
      in increased levels of Ptc mRNA. Gli, but not Gli2, is also upregulated,
      suggesting a differential involvement of the Gli genes in the regulation of Ptc
      by SHH during lung development. Gli3 is not upregulated by Shh overexpression.
      However, its importance for lung development is shown by the finding that Gli3XtJ
      embryos, homozygous for a mutation involving a deletion of the Gli3 gene, have a
      stereotypic pattern of abnormalities in lung morphogenesis. The pulmonary defects
      in these embryos, consisting of localized shape changes and size reductions,
      correlate with normal Gli3 expression. Thus, our data indicate that one of the
      Gli genes, Gli3, is essential for normal lung development, and that another, Gli,
      can be placed downstream of Shh signaling in the lung.

PMID- 9268580
TI  - Different MRF4 knockout alleles differentially disrupt Myf-5 expression: cis
      regulatory interactions at the MRF4/Myf-5 locus.
AB  - Three different null alleles of the myogenic bHLH gene MRF4/herculin/Myf-6 were
      created recently. The three alleles were similar in design but were surprisingly
      different in the intensity of their phenotypes, which ranged from complete
      viability of homozygotes to complete lethality. One possible explanation for
      these differences is that each mutation altered expression from the nearby Myf-5
      gene to a different extent. This possibility was first raised by the observation
      that the most severe MRF4 knockout allele expresses no Myf-5 RNA and is a
      developmental phenocopy of the Myf-5 null mutation. Furthermore, initial studies
      of the two weaker alleles had shown that their differences in viability correlate
      with the intensity of rib skeletal defects, and the most extreme version of this
      rib defect is the hallmark phenotype of Myf-5 null animals. In the present study
      we tested this hypothesis for the two milder MRF4 alleles. By analyzing compound
      heterozygous animals carrying either the intermediate or the weakest MRF4
      knockout allele on one chromosome 10 and a Myf-5 knockout allele on the other
      chromosome, we found that both of these MRF4 alleles apparently downregulate Myf
      5 expression by a cis-acting mechanism. Compound heterozygotes showed increased
      mortality of the normally viable MRF4 allele, together with intensified rib
      defects for both MRF4 alleles and increased deficits in myotomal Myf-5
      expression. The allele-specific gradation in phenotypes also suggested that rib
      morphogenesis is profoundly sensitive to quantitative differences in Myf-5
      function if Myf-5 products drop below hemizygous levels. The mechanistic basis
      for cis interactions at the MRF4/Myf-5 locus was further examined by fusing a DNA
      segment containing the entire MRF4 structural gene, including all sequences
      deleted in the three MRF knockout alleles, with a basal promoter and a lacZ
      reporter. Transgenic embryos showed specific LacZ expression in myotomes in a
      pattern that closely resembles the expression of Myf-5 RNA. cis-acting
      interactions between Myf-5 and MRF4 may therefore play a significant role in
      regulating expression of these genes in the early myotomes of wildtype embryos.

PMID- 9268582
TI  - EDITORIAL

PMID- 9268581
TI  - Novel expression gradients of Eph-like receptor tyrosine kinases in the
      developing chick retina.
AB  - Eph-like receptor tyrosine kinases have recently been identified as critical
      components in the development of the retinotectal system. Complementary gradients
      of receptors and ligands in the retina and tectum, and within the retina itself,
      have previously been described. Here, we present a novel centroperipheral
      gradient of expression for one member of this family of receptors, Cek9,
      suggesting that retinal patterning and axon guidance during the establishment of
      retinotectal projections may involve coordinate mapping along three axes.
      Furthermore, we show matching gradients of two cytoplasmic kinases, compatible
      with their putative involvement in the intracellular signaling pathways used by
      these receptors in the retina. We also demonstrate a dorsal to ventral expression
      gradient for Cek11, an Eck-like receptor, the Eph subclass previously suggested
      to specify positional information along the temporonasal axis.

PMID- 9268583
TI  - Erbium: YAG laser trabecular ablation with a sapphire optical fiber.
AB  - The purpose of the study was to evaluate the effect of erbium (Er): yttrium
      aluminum garnet (YAG) laser trabecular ablation with a sapphire optical fiber on
      outflow facility. After obtaining baseline outflow facility using a computerized
      differential pressure perfusion system, human cadaver eyes were subjected to Er:
      YAG laser trabecular ablation using a sapphire optical fiber. Single pulses at
      varying energy levels (10 to 20 mJ pulse-1) were applied in a nearly contiguous
      fashion over four clock hours of meshwork. Post-laser outflow facility was then
      determined utilizing the same perfusion system and histopathologic analysis
      performed. Of the ten eyes, nine were perfused to steady baseline facility. One
      eye was excluded from the study because of a leak in our system during the
      initial perfusion. The mean baseline facility was 0.283+/-0.08 microl min-1 mmHg
      1. There was a significant increase in outflow facility after trabecular
      ablation, with a mean post-laser facility of 0.62+/-0.15 microl min-1 mmHg-1
      (P=0.01). Eyes which received a sham treatment showed no increase or a minimal
      increase in facility. Histopathologic analysis revealed ablation into Schlemm's
      canal with some thermal damage to the outer wall at all energy levels. Er: YAG
      laser trabecular ablation with a sapphire fiber is capable of increasing outflow
      facility in human cadaver eyes.

PMID- 9268584
TI  - Cellular localisation and dynamics of nitric oxide synthase expression in the rat
      anterior segment during endotoxin-induced uveitis.
AB  - The present study examined the temporal pattern and cellular localisation of
      nitric oxide synthase in Endotoxin-Induced Uveitis (EIU). Lewis rats (n=40)
      received a single footpad injection of 200 microg of bacterial
      lipopolysaccharide. Animals were killed at 0, 2, 4, 6, 12, 24, 48 and 72 hr after
      injection and ocular tissues prepared as iris-ciliary body wholemounts or frozen
      sections of the anterior segment. The expression of constitutive nitric oxide
      synthase (cNOS) and inducible nitric oxide synthase (iNOS) was investigated at
      all time points by immunohistochemistry. A further group of animals (n=6) were
      killed at the peak of the disease (12 hr) and the cellular co-localisation of
      iNOS on resident and infiltrating immune cells was investigated by double
      immunohistochemistry utilising the biotinylated monoclonal antibodies ED1, ED2
      and Ox6. Expression of cNOS on iris vessels did not alter during the course of
      EIU. Quantitative analysis of iris-ciliary body wholemounts revealed the first
      evidence of iNOS+ at 2 hr which increased dramatically at 4 and 6 hr with a peak
      at 12 hr. The expression of iNOS in the early phase of the disease (2-6 hr) was
      associated with small round marginating and newly extravasated cells that on
      morphological criteria were most likely neutrophils and monocytes. At 12 hr,
      cells of more mixed morphologies began to express iNOS and double labelling
      revealed 70% of these cells were also ED1(+) (a lysosomal antigen present in
      monocytes/macrophages and dendritic cells), 52% were Ox6(+) (MHC class II)
      (dendritic cells, activated macrophages and some T-cells) and 19% were ED2(+)
      (pan-specific resident tissue macrophages). Expressed in an alternative manner,
      10% of the total ED1(+) cell population, 11% of the ED2(+) cells and 44% of
      Ox6(+) cells co-expressed iNOS. Expression of iNOS decreased significantly by 24
      hr to near baseline levels and was absent by 48 and 72 hr. Within the ciliary
      processes iNOS+ dendriform cells were noted at 6 hr and accumulations of many
      small round iNOS+ cells were present at 12 hr. The ciliary epithelium did not at
      any time express iNOS at the protein level detectable by immunohistochemistry.
      The results of this study suggest that iNOS expression early in EIU is associated
      with infiltrating or newly recruited neutrophils and monocytes/macrophages in the
      iris whereas later in the disease resident tissue macrophages and MHC class II+
      cells (activated macrophages and putative dendritic cells) in the iris and
      ciliary body may synthesise nitric oxide. The role of this late phase of nitric
      oxide synthesis may include lymphocytostasis and immunosuppression as proposed in
      other tissue sites. The outcome of the present study may help in planning
      therapeutic strategies using NOS inhibitors.

PMID- 9268585
TI  - Conjunctival fibrosis in ocular cicatricial pemphigoid--the role of cytokines.
AB  - Ocular cicatricial pemphigoid (OCP) is a systemic, autoimmune disease
      characterised by conjunctival scarring that is often progressive. The
      pathophysiology of the fibrosis is unknown. This study aimed to determine which
      fibrogenic cytokines are present in the conjunctiva in patients with acute and
      chronic OCP as a first stage in determining the mechanisms of fibrosis.
      Conjunctival biopsies from patients with acute, subacute and chronic OCP (n=13)
      were compared to normal conjunctiva (n=10). Production of mRNA for, and
      expression of, transforming growth-beta1, 2 and 3 (TGF-beta), TGF-beta receptor,
      platelet derived growth factor (PDGF) and fibroblast growth factor (FGF) were
      assessed using in situ hybridisation and immunohistochemistry. Acute disease
      showed increased levels of mRNA for TGF-beta1 and 3, mainly in stromal
      fibroblasts and macrophages. In the stroma, there were concordant increases in
      latent and activated TGF-beta1 and 3 and TGF-beta receptor expression by
      fibroblasts. There were no significant increases in the expression of TGF-beta2,
      PDGF or FGF in acute disease. No cytokines or receptors were significantly
      increased in chronic disease. Acutely inflamed conjunctiva in OCP is associated
      with significant stromal levels of TGF-beta1 and 3 but not PDGF or FGF and none
      were increased in chronic disease. This suggests that TGF-beta may have a key
      role in the pathogenesis of the fibrosis. The absence of fibrogenic cytokines in
      chronic progressive OCP provides support for the proposal that fibroblasts in OCP
      conjunctiva may remain functionally and morphologically abnormal after the
      withdrawal of cytokine influences.

PMID- 9268586
TI  - Intraocular pressure and outflow facility are unchanged following acute and
      chronic intracameral chondroitinase ABC and hyaluronidase in monkeys.
AB  - We determined the effect of chronic and acute loss of glycosaminoglycans from the
      aqueous outflow pathway on intraocular pressure (IOP) and outflow facility in the
      subhuman primate eye. For the study of the chronic effects of the GAGases,
      cynomolgus monkeys received intracameral injections of hyaluronidase
      (Streptomyces, 5 or 50 units, n=2) or chondroitinase ABC (0.05 or 0.25 units,
      n=2) biweekly for 8 months (4 months for each dose). IOP was measured at 3, 7, 10
      and 14 days after each injection. Outflow facility (2-level constant pressure)
      was determined at 2, 4, 6, and 8 months. Monkeys were killed 6 days after the
      last injection. The changes in the distribution of hyaluronic acid and sulfated
      proteoglycans in the outflow pathway were examined using substrate-specific
      histochemical techniques. The acute effects of these enzymes on outflow
      facilities (30 min or 2 hr after enzyme) were determined in another group of
      animals (n=4 for each time enzyme-1). IOP and outflow facility were unchanged
      compared to controls (heat inactivated enzyme) at any time in the chronically or
      acutely treated monkeys. Hyaluronic acid staining was absent in the outflow
      pathways of eyes treated chronically with hyaluronidase compared with control
      eyes, while collagen-associated sulfated proteoglycans were decreased but not
      completely removed by the chronic chondroitinase ABC treatment. Chronic loss of
      these glycosaminoglycans from the trabecular meshwork does not appear to
      contribute to the IOP elevation and decrease in outflow facility that accompanies
      open-angle glaucoma. Most importantly, no increase in outflow facility was found
      with acute hyaluronidase or chondroitinase treatment.

PMID- 9268587
TI  - Potassium current oscillations across the rabbit lens epithelium.
AB  - Rabbit lenses expressing spontaneous oscillations in translens short-circuit
      current (Isc) are obtained somewhat frequently, with this phenomenon observed in
      approximately 30% of isolated lenses as described earlier (Exp. Eye Res. 61, 129
      140, 1995). Since pharmacological protocols to consistently elicit Isc
      oscillations were not found, characterizations of the underlying transport
      processes have been limited to the application of various inhibitors on the
      spontaneous phenomenon. The present report extends the initial observations by
      confirming that oscillations are immediately inhibited upon the anterior addition
      of the Ca2+ channel blocker nifedipine (10 microM), and by demonstrating that
      other treatments which should affect epithelial Ca2+ homeostasis are also
      inhibitory (e.g., Bay K 8644 (10 microM), diltiazem (10 microM), EGTA (2 mm), and
      Ca2+-free media). Furthermore, Isc oscillations are immediately inhibited by the
      K+ channel blocker, Ba2+, but not by the Na+-K+ pump inhibitor, ouabain. The
      intracellular Ca2+ mobilizing agents thapsigargin (0.1 microM) or acetylcholine
      (1 microM) modified but did not permanently inhibit the oscillations, confirming
      earlier observations. At 50 microM, however, acetylcholine addition was
      inhibitory, but reversible, for oscillations restarted upon its subsequent
      removal. In addition, lens oscillations were also characterized under open
      circuit conditions with microelectrodes inserted in the superficial cells near
      the equator of lenses isolated in a divided chamber. The potential difference
      (PD) across each lens face was recorded, as was the translens PD (PDt), which
      equals the difference between the PDs across each lens surface. Oscillations in
      PDt were obtained in 7 of 26 lenses. The oscillations arose only from an
      oscillation in the PD across the anterior face (PDa). While PDa and PDt
      oscillated with the same amplitude (approximately 12 mV) and period
      (approximately 70 sec), the PD across the posterior surface remained stable.
      During these oscillations the conductance of the anterior surface was maximal at
      the most positive voltage of the anterior bath with respect to the lens interior
      (46 mV), whereas, minimal conductance occurred at the least positive PDa (34 mV).
      Overall, these observations are consistent with the likely presence of voltage
      operated Ca2+ channels in parallel with various Ca2+-sensitive K+ channels in the
      epithelial basolateral membrane. A model to explain the oscillatory pattern
      across the anterior face while the PD across the posterior face remains unaltered
      is presented.

PMID- 9268588
TI  - Fourier transform analysis of human corneal endothelial specular
      photomicrographs.
AB  - Fourier analysis of in vivo human corneal endothelial cell structure was
      investigated using specular photomicrographs for a range of ages from less than
      one year to over 70. The theoretical basis for this analysis was investigated
      using mathematical models of cell structures where the elements determining their
      form could be modified in a controlled and quantified manner. The resulting
      Fourier transform properties were related to properties of cell structure. The
      experimental factors underlying this analysis were then studied using digitized
      images of corneal endothelial cells. It was found that the Fourier transforms
      provided quantitative descriptions of population cell size and organisation. For
      the smaller, more regular cell structure from the younger eyes, the expected
      larger rings of the Fourier transforms were demonstrated. Specular
      photomicrographs of older eyes gave rise to smaller diameter rings in their
      Fourier transforms. These results are consistent with the previous studies which
      used manual tracings of human endothelial cell patterns. This is the first
      demonstration of the direct Fourier analysis of clinical human corneal specular
      photomicrographs.

PMID- 9268589
TI  - ERG abnormalities in relation to histopathologic findings in vitiligo mutant
      mice.
AB  - The vitiligo, mivit, mutation has several prenatal and perinatal effects on
      development of the retinal pigment epithelium, and later, leads to extensive,
      progressive degeneration of photoreceptor cells in the neural retina of
      homozygous affected mice. The aim of the present study was to determine by
      functional criteria how early can abnormalities be detected in the neural retina.
      Electroretinograms (ERGs) were correlated with histopathological findings in the
      same animals. Congenic homozygous mutants, heterozygotes, and homozygous wild
      type mice were studied at 2, 3, 6, 24 and 56 weeks of age, the same animals being
      tested serially at the three older time points. The nontested eye of each animal
      was embedded in Epon and sectioned at 1 micron for light microscopic study. ERG
      recordings from vitiligo homozygotes differed from heterozygous and wild-type
      mice, but the latter two groups did not differ from each other. As early as two
      weeks of age, homozygous mutants showed a significant reduction of rod dominated
      maximum ERG a-wave and b-wave amplitude. ERG b-wave sensitivity (sigma) was
      significantly reduced, and ERG implicit times were delayed for homozygous mutants
      at 3 (a-wave) and 6 (b-wave) weeks of age. This is the first study to report
      reduced and delayed ERG a-waves and b-waves in this animal model, like the early
      functional abnormalities in human retinitis pigmentosa, and also the first to
      show short and disoriented rod outer segments, beginning retinal separation from
      the pigment epithelium, and a few macrophage-like cells already present in the
      subretinal space at 2 weeks of age (in three of four homozygous mutant eyes
      examined). Given these early functional and structural abnormalities in the
      neural retina, it remains to be determined whether the mi gene targets the
      retinal pigment epithelial cell, the photoreceptor cell, or both.

PMID- 9268590
TI  - Phosphorylation of HSP25 during lens cell differentiation.
AB  - Small heat shock proteins and alpha-crystallins are related proteins with several
      common structural and functional properties including homologous amino acid
      sequences and similar chaperone-like activity. Furthermore, small heat shock
      proteins and alpha-crystallins are phosphorylated in vivo at serine residues
      within homologous amino acid sequences. During the differentiation of lens
      epithelial cells to fiber cells, significant changes in the patterns of
      expression and phosphorylation of alpha-crystallins take place, leading to the
      accumulation of phosphorylated forms of these proteins in lens fiber cells. To
      determine whether the small heat shock protein HSP25 undergoes phosphorylation in
      lens cells and to ascertain whether its phosphorylation state changes during lens
      cell differentiation, a comparative analysis of the HSP25 phosphorylation pattern
      in epithelial and fiber cells was undertaken. Analysis of phosphorylated and non
      phosphorylated forms of HSP25 was carried out in cell extracts from rat lens
      epithelium and cortex by isoelectric focusing and Western blot using an antibody
      specific for the recombinant murine protein. The phosphorylated forms were
      identified by their isoelectric points and the characteristic shift upon in vitro
      dephosphorylation with phosphoprotein phosphatase 2B. HSP25 accounted for up to
      2.4% of the protein content of rat lens extracts where it was present
      predominantly in mono- and bi-phosphorylated forms. Compared to epithelial cells
      extracts, the fiber cells extracts contained 67% more total HSP25 and a
      significantly higher proportion of bi-phosphorylated form. Phosphorylated HSP25
      was sensitive to dephosphorylation by phosphoprotein phosphatase 2B in both cell
      extracts but the apparent dephosphorylation rate was significantly slower in the
      fiber cell extracts. The results demonstrate that HSP25 is phosphorylated in the
      lens in vivo. Furthermore, synthesis and phosphorylation of HSP25 change with
      lens cell differentiation resulting in a significant accumulation of bi
      phosphorylated form in the fiber cells. These findings indicate that HSP25 and
      its phosphorylation may have important roles in lens cell differentiation.

PMID- 9268591
TI  - Age-related increase in activity of specific lysosomal enzymes in the human
      retinal pigment epithelium.
AB  - Age related changes in the activity of lysosomal enzymes have been studied in the
      cultured human retinal pigment epithelium cells collected from 26-85 year old
      donors. Among four such enzymes studied, activities of cathepsin D and beta
      glucuronidase increased with the age of the donors while no notable change in
      activity of arylsulfatase B and alpha-mannosidase was observed. Kinetic
      parameters of beta-glucuronidase was measured in retinal pigment epithelium cells
      isolated from donors of different ages. Similar kinetic parameters for beta
      glucuronidase at different ages suggest that the observed increase in the
      activity of the enzyme with age is not due to post-translational modification of
      the enzyme. Western blot analysis provides evidence for increased synthesis of
      beta-glucuronidase with aging. Relative proportions of glycosaminoglycans, the
      natural substrates of beta-glucuronidase and arylsulfatase B, in the retinal
      pigment epithelium altered with the age of the donors. A significant decrease of
      dermatan sulfate levels with aging correlates well with the observed increase in
      the level of beta-glucuronidase activity.

PMID- 9268592
TI  - Mechanical injury increases bFGF and CNTF mRNA expression in the mouse retina.
AB  - We characterized the survival-factor response of the normal mouse retina to
      mechanical injury by examining the expression of mRNAs for basic fibroblast
      growth factor (bFGF), ciliary neurotrophic factor (CNTF), and their receptors,
      FGF receptor-1 (FGFR-1) and CNTF receptor alpha (CNTFR-alpha). The retina was
      injured by making an incision through the choroid and retinal pigment epithelium
      that penetrated the subretinal space of each eye of an adult BALB/c mouse.
      Retinas were taken 6 hr, 12 hr, 1, 2, 4, 7, 10 and 16 days post-injury. Control
      animals were without injury. Northern blot analysis was performed to determine
      bFGF, CNTF and their receptor mRNA levels. A significant increase in bFGF and
      CNTF mRNAs was observed after injury, along with an increase in glial fibrillary
      acidic protein (GFAP) expression. More than 2-fold of upregulation of bFGF mRNA
      was seen as early as 6 hr after injury. This increase reached a maximum of more
      than 5-fold at day 2 post-injury and then declined slowly, and was still about
      2.5-fold of the control level by day 16. Expression of CNTF showed a small
      increase of about 1.6-fold at 6 hr after injury. The upregulation reached a peak
      level of about 2.7-fold at day 4 after injury, then declined to control level by
      day 16. There was only a very small increase in FGFR-1 at 6, 12 and 24 hr after
      injury, and no significant increases in FGFR-1 at time points longer than 1 day
      post-injury. Expression of GFAP followed a time course similar to that of bFGF.
      We conclude that mechanical injury induces bFGF, CNTF, and GFAP expression in the
      mouse retina with time courses similar to the upregulation of these molecules in
      rat retina. Compared to the upregulation in rat retina, however, the injury
      induced upregulation of bFGF and GFAP is much less in the mouse retina. In
      addition, there was only a very small induction of FGFR-1 expression in the mouse
      retina. These findings may explain, at least in part, the lack of injury-induced
      photoreceptor protection in the mouse retina.

PMID- 9268593
TI  - Evaluation of the rhodopsin kinase gene in patients with retinitis pigmentosa.
AB  - We explored the possibility that defects in the rhodopsin kinase gene might cause
      retinitis pigmentosa (RP) by evaluating 160 unrelated cases with dominant RP and
      151 unrelated cases with recessive RP. One of five missense changes was
      discovered in each of six cases of dominant RP, but none of the missense changes
      cosegregated with disease among relatives. Heterozygous missense changes were
      found in two cases of recessive RP, and a heterozygous frameshift mutation was
      found in one additional case of recessive RP. Although the same DNA sequence
      alterations could be found heterozygously in the only affected sibling of each
      index case of recessive RP, no defect could be found in the other allele. Hence,
      none of the changes found in the cases of dominant or recessive RP was proven to
      be a cause of RP. The data indicate that defects in the rhodopsin kinase gene
      causing RP are either rare or nonexistent.

PMID- 9268594
TI  - Preliminary studies on the aggregation process of alpha-crystallin.
AB  - The mechanism by which alpha-crystallin subunits form the native 800 kD aggregate
      is currently unknown. Experiments were performed to investigate the mechanism for
      this process. Gel-filtration Fast Performance Liquid Chromatography (FPLC) and
      Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE), with and
      without cross-linking with glutaraldehyde, indicate that alpha-crystallin
      undergoes a concentration-dependent aggregation process. The denaturation of
      alpha-crystallin, and its subsequent renaturation and reaggregation, lead to the
      formation of several different species. At very low concentrations (< 0.5
      microM), only monomeric and/or dimeric species exist. With a ten-fold increase in
      alpha-crystallin concentration from 0.05 microM to 0.5 microM, the amount of the
      monomeric/dimeric species increases to a plateau coincident with the appearance
      of a tetrameric species at 0.5 microM. With an additional ten-fold increase in
      concentration from 0.5 microM to 5 microM, the amount of the tetrameric species
      increases and levels off to its own plateau coincident with the appearance of the
      native 800 kD alpha-crystallin aggregate at 5 microM. The amount of the native
      species is extremely small at this concentration, but increases sharply and
      linearly with increasing concentration, while the concentrations of
      monomeric/dimeric and tetrameric species remain constant. The concentration at
      which the relative amount of the native species begins to increase sharply is
      within the range of the critical micelle concentration previously characterized.

PMID- 9268595
TI  - Contribution of osmotic changes to disintegrative globulization of single
      cortical fibers isolated from rat lens.
AB  - In this study the contribution of osmotic changes to disintegrative globulization
      of lens cortical fibers was examined. Single fiber cells were isolated by
      trypsinization of adult rat lens cortex, and morphological changes elicited by
      exposure to different external solutions were monitored optically. The survival
      of the fiber-shaped cells was analysed in accordance with the Weibull
      distribution. Changes in [Ca2+]i were measured using the fluorescent calcium
      sensitive dye-Fluo-3. Exposure of isolated fiber cells to Ringer's solution
      (containing 2 mm Ca2+) led to an exponential increase in [Ca2+]i with a time
      constant of 10.2+/-0.8 min, and caused disintegrative globulization in 25+/-4 min
      (=Tg). The process of globulization as well as the rate of increase in [Ca2+]i
      was delayed by removing Cl- ions from the external media. Globulization was also
      delayed by adding 20% bovine serum albumin (Tg=107+/-3 min) or chloride channel
      inhibitors 5, nitro-2-(3-phenylpropylamino) benzoate (NPPB), dideoxyforskolin,
      niflumic acid, and tamoxifen. When the fiber cells were suspended in isotonic
      (280 mm sucrose) HEPES-sucrose (HS) or HEPES-EDTA-sucrose (HES) solution, no
      globulization was observed for an observation time of 120 min. However, exposure
      to hypotonic (180 mm) HES solution led to disintegration of fiber cells in 75+/-7
      min. Disintegration of the fiber induced by hypotonic HES solution could be
      delayed by either 0. 05 mm leupeptin (Tg=97+/-6 min) or by pre-loading the fibers
      with BAPTA (Tg=100+/-4 min). Inhibition of membrane calcium transport by 0.5 mm
      La3+ had no effect on Tg in hypotonic HES. Addition of 2 mm Ca2+ to HES solution
      accelerated globulization, and Tg was 57+/-4, 69+/-5 and 102+/-6 min for hypo-,
      iso- and hyper- tonic solutions, respectively. Transient exposure to calcium also
      accelerated disintegrative globulization of fiber cells exposed subsequently to
      HES solution. These results suggest that in ionic media, part of the calcium
      influx in isolated fiber cells is mediated by the influx of chloride ions. In the
      absence of other ions, the fiber cells still accumulate calcium, although this
      calcium influx was independent of medium tonicity. Globulization-induced by
      hypotonic sucrose solution appears to be mediated by the activation of
      intracellular proteases and by cell swelling-induced release of calcium from
      internal stores. Such swelling-mediated disintegrative globulization of fiber
      cells may be of significance in understanding the cellular basis of diabetic
      cataracts.

PMID- 9268596
TI  - Porcine iris pigment epithelial cells can take up retinal outer segments.
AB  - This study investigates the ability of iris epithelial cells (IPE) to ingest rod
      outer segments (ROS) and compares the amount of phagocytosis of porcine RPE and
      IPE cells by the use of a pH sensitive fluorescent dye (carboxy SNAFL) at the
      light microscopic level. The dye allowed investigation of ingestion separately
      from binding of rod outer segments. In a second set of experiments, after
      exposing ferritin-labeled ROS to the cultured cells, phagosomes were also counted
      in electron microscopic sections. Additionally immunocytochemical staining was
      performed with IPE and RPE cells. Both cell types stained positive with
      polyclonal NaK-ATPase antibodies against the alpha 1 subunit from rat brain and
      kidney. The epithelial nature of the cultured cells was determined by monoclonal
      anti-human-cytokeratin antibodies. Moreover, the ultrastructure of the cells
      revealed high amounts of phagosomes smaller than 1 micron in diameter present in
      both RPE and IPE cells. The iron label of the phagosomes was determined by EELS
      spectra taken from individual phagosomes. Electron and light microscopic
      quantification shows that cultured IPE cells have 64% of the phagocytic capacity
      of the RPE with respect to phagosomes larger than 1 micron in diameter.

PMID- 9268597
TI  - Gene expression of proteases and protease inhibitors in the human ciliary
      epithelium and ODM-2 cells.
AB  - Complementary DNAs (cDNAs), corresponding to the human proteinases cathepsins D
      and O and proteinase inhibitors alpha2-macroglobulin and PP5/TFPI-2, have
      recently been isolated and identified from a subtractive human ciliary body
      library. In the present study we determined: (i) their pattern of expression in
      the human eye; (ii) the ability of the ciliary body and/or ciliary epithelial
      cells to synthesize and secrete cathepsin D and alpha1-antitrypsin in vitro; and
      (iii) whether alpha1-antitrypsin expression in cultured ciliary epithelial cells
      is modulated by protein kinase C activation. Northern analysis demonstrated that
      the ciliary body expresses high levels of cathepsins D and O, alpha2
      macroglobulin, alpha1-antitrypsin and PP5/TFPI-2 transcripts. Western blot
      analysis and immunoprecipitation experiments with cathepsin D and alpha1
      antitrypsin antibodies indicated that metabolically labeled ciliary body explants
      and/or ciliary epithelial cells in vitro with 35S-methionine, synthesize and
      secrete these proteins. Cultured nonpigmented ciliary epithelial ODM-2 cells, in
      response to phorbol-12-myristate 13-acetate (PMA), but not to the non-protein
      kinase C binding phorbol ester 4 alpha-phorbol didecanoate (PDBu), elicited up
      regulation (up to 5-fold) of transcription, synthesis and secretion of alpha1
      antitrypsin. These results provide in vitro evidence that the ciliary epithelium
      synthesizes and secretes a selective group of proteinases and proteinase
      inhibitors detected also in aqueous humor. The expression of at least of one of
      the proteinase inhibitors, alpha1-antitrypsin, can be modulated in response to
      phorbol ester.

PMID- 9268598
TI  - Canine rod photoreceptor cGMP-gated channel protein alpha-subunit: studies on the
      expression of the gene and characterization of the cDNA.
AB  - Rod photoreceptor cyclic GMP gated-channel protein is a key component of the
      visual transduction cascade in the vertebrate retina. The protein is composed of
      at least two subunits (alpha and beta). Mutations in the alpha-subunit (CNGC1)
      have been shown to cause retinitis pigmentosa (RP) in humans. Several
      heterogeneous canine retinal diseases, which are clinically similar to RP, are
      known collectively as progressive retinal atrophy (PRA) and occur in dogs in a
      breed-specific manner. For the purpose of examining CNGC1 gene as a candidate for
      PRA, we report here the characterization of canine CNGC1 cDNA, and examine the
      expression of the gene in different tissues by northern analysis, reverse
      transcription and polymerase chain reaction (RT-PCR), and retinal
      immunocytochemistry. The characterized canine CNGC1 cDNA sequence contains 2717
      nucleotides which include 211 bp 5"-untranslated region and 430 bp 3"
      untranslated region including the poly A tail. It is predicted to encode a
      protein containing 691 amino acids which include six putative transmembrane
      domains, a pore loop and a cGMP binding domain as well as one potential
      extracellular site for N-linked glycosylation. Over the coding region, the canine
      CNGC1 shares 85-90% identity in the nucleotide sequence and 91-94% identity in
      the deduced amino acid sequence with its homologues in other mammalian species.
      However, the homology drops to only 71% and 78% of shared nucleotide and
      predicted amino acid sequences, respectively, when compared to the chicken CNGC1.
      Among all the tissues examined the gene is expressed at a much higher level in
      retina as a major transcript of 3.5 kb length. In addition, another minor
      transcript (9.8 kb) is consistently observed in the canine retinal RNA which may
      represent the canine homologue of the rod specific beta-subunit of the cyclic
      nucleotide-gated channel protein. Transcripts were detected only in retina by
      northern analysis but low level of expression of CNGC1 was detected in liver,
      kidney, heart and brain by RT-PCR. The expression of the CNGC1 protein was found
      to be localized specifically to the photoreceptor outer segment by
      immunocytochemistry.

PMID- 9268599
TI  - Superoxide radical production stimulates retroocular fibroblast proliferation in
      Graves' ophthalmopathy.
AB  - Retroocular fibroblast proliferation is believed to be a key component in the
      pathogenesis of Graves' ophthalmopathy. In the present study, we assessed the
      ability of superoxide radicals, generated using the xanthine oxidase/hypoxanthine
      system to induce cellular proliferation in cultured human retroocular fibroblasts
      obtained from two patients with severe Graves' ophthalmopathy and two control
      patients undergoing corrective eye surgery. In tissue obtained from patients with
      Graves' ophthalmopathy, fibroblast proliferation, as assessed by [3H]-thymidine
      incorporation, was induced by superoxide radicals in a dose-dependent manner.
      Xanthine oxidase or hypoxanthine alone had no proliferative effect, and control
      retroocular fibroblasts showed no proliferation in response to superoxide
      generation. Preincubation with the antithyroid drug methimazole, at
      concentrations ranging from 0-25 microM, prevented superoxide-induced fibroblast
      proliferation in a dose-response pattern. Preincubation with the xanthine oxidase
      inhibitor, allopurinol (1.0 mM) or the antioxidant nicotinamide (10 microM) also
      inhibited superoxide-induced fibroblast proliferation, whereas propylthiouracil
      (10 microM) had little effect. These studies suggest a pathway through which
      oxygen free radicals may contribute to the retroocular fibroblast proliferation
      observed in patients with Graves' ophthalmopathy.

PMID- 9268600
TI  - An exchange of views on culling.

PMID- 9268602
TI  - The cult of culling.
AB  - It is difficult to understand why culling (reduction of litter size) has become
      such a widely used procedure in reproductive toxicity studies since there appear
      to have been no prior investigations to ascertain that it would improve the
      efficiency of studies with respect to detecting adverse effects. Perhaps the only
      provable advantage of culling is with respect to economics and convenience. Post
      hoc rationalizations for culling lack conviction because many of the claims made
      for culling are erroneous, inconsistent, vague, and contradictory. Mostly, they
      are based on part truths derived from minimal studies, conducted for totally
      different purposes. That experimental animals have to be killed sooner or later
      is unquestioned, but for ethical and scientific reasons, it is imperative that
      the maximum amount of information is obtained from them. Currently, the most
      common practice is to cull litters to four per sex (total eight) on Day 4
      postpartum. This is totally divorced from natural values for most rat strains and
      involves elimination, usually without adequate examination, of between 30 and 45%
      of offspring. Without culling most of these would survive, unless there was a
      treatment effect. Intuitively, it would seem that removal of such a proportion of
      offspring would severely limit the possibility of detecting the postnatal
      equivalent of fetal malformations. Culling totally nullifies litter size as an
      indicator of toxicity. Indirectly, it also nullifies the value of mean pup weight
      as an indicator of toxicity because it greatly increases the variation in mean
      pup weight. This is quite contrary to the claim that culling reduces variance.
      Further, the increased growth of offspring in culled litters can have long-term
      consequences of a shorter overall and reproductive life span.

PMID- 9268601
TI  - The rationale for culling of rodent litters.
AB  - Based on a review of the pertinent literature and our own unpublished data, it is
      recommended that culling of rodent litters in the early postnatal period should
      be a standard practice in delivery-type reproduction studies. This, in turn, will
      reduce the litter size-induced variability in the growth and development of pups
      during the postnatal period and thus increase the sensitivity of statistical
      analyses to detect treatment-related effects. This will also ensure that any
      adverse effects on pup growth (body weight gain) and development (reflex and
      behavior development) are not masked by a treatment-induced reduction in litter
      size. The culling should be carried out randomly and no attempt should be made to
      selectively cull sick or underweight pups. Since male pups weigh significantly
      more than females and studies have shown differences in maternal behavior toward
      one sex over the other, whenever possible each culled litter should consist of an
      equal number of males and females.

PMID- 9268603
TI  - Mitochondria-mediated cell injury. Symposium overview.
AB  - Mitochondria have long been known to participate in the process of cell injury
      associated with metabolic failure. Only recently, however, have we come to
      appreciate the role of mitochondria as primary intracellular targets in the
      initiation of cell dysfunction. In addition to ATP synthesis, mitochondria are
      also critical to modulation of cell redox status, osmotic regulation, pH control,
      and cytosolic calcium homeostasis and cell signaling. Mitochondria are
      susceptible to damage by oxidants, electrophiles, and lipophilic cations and weak
      acids. Chemical-induced mitochondrial dysfunction may be manifested as diverse
      bioenergetic disorders and considerable effort is required to distinguish between
      mechanisms involving critical mitochondrial targets and those in which
      mitochondrial dysfunction is secondary and plays only a modulatory role in cell
      injury. The following paragraphs review a few important examples of chemical
      induced cytotoxic responses that are manifested as interference with
      mitochondrial metabolism and bioenergetics, gene regulation, or signal
      transduction in the form of apoptosis and altered cell cycle control. Greater
      understanding of the molecular mechanisms of mitochondrial bioenergetics, ion
      regulation, and genetics will lead to numerous additional examples of
      mitochondria-mediated cell injury, revealing important new insight regarding the
      prediction, prevention, diagnosis, and treatment of chemical-induced toxic tissue
      injury.

PMID- 9268604
TI  - Assessment of immunotoxicity by multiparameter flow cytometry.
AB  - Flow cytometry is a unique technology useful in the examination of effects of
      immunotoxic agents on target cells of the immune system. The purpose of this
      workshop was to provide an overview of the use of flow cytometry in new and
      established models of immunotoxicity, with emphasis on the potential
      applications, assay validation, and potential pitfalls. This overview begins with
      a discussion of methods useful in the assessment of Ca2+-dependent mechanisms of
      lymphoid cell activation in surface marker-defined human B cells, T cells, and
      monocytes. A discussion of the use of flow cytometry in analysis of apoptosis is
      also presented in this paper. The second paper presents data on the development
      and use of flow cytometry as an alternative to a Cr51 release assay for an
      assessment of cytotoxic T cell activation. The use of surface markers for
      characterizing and distinguishing the effects of chemical irritants from
      sensitizers is next presented, followed by an overview of the use of fluorescent
      probes to assess cell thiol status and overall oxidant-induced injury to lymphoid
      cells. Finally, an interlaboratory study designed to compare and evaluate the use
      of flow cytometry procedures in rat splenic cell subtyping is presented. Overall,
      these studies demonstrate the utility of flow cytometry assays in
      immunotoxicologic research, but further efforts are needed in the validation of
      many of these assays for routine use in immunotoxicologic testing.

PMID- 9268605
TI  - Acetylcholinesterase and neuropathy target esterase inhibitions in neuroblastoma
      cells to distinguish organophosphorus compounds causing acute and delayed
      neurotoxicity.
AB  - The differential inhibition of the target esterases acetylcholinesterase (AChE)
      and neuropathy target esterase (NTE, neurotoxic esterase) by organophosphorus
      compounds (OPs) is followed by distinct neurological consequences in exposed
      subjects. The present study demonstrates that neuroblastoma cell lines (human SH
      SY5Y and murine NB41A3) can be used to differentiate between neuropathic OPs
      (i.e., those inhibiting NTE and causing organophosphorus-induced delayed
      neuropathy) and acutely neurotoxic OPs (i.e., those highly capable of inhibiting
      AChE). In these experiments, concentration-response data indicated that the
      capability to inhibit AChE was over 100x greater than the capability to inhibit
      NTE for acutely toxic, nonneuropathic OPs (e.g., paraoxon and malaoxon) in both
      cell lines. Inhibition of AChE was greater than inhibition of NTE, without
      overlap of the concentration-response curves, for OPs which are more likely to
      cause acute, rather than delayed, neurotoxic effects in vivo (e.g., chlorpyrifos
      oxon, dichlorvos, and trichlorfon). In contrast, concentrations inhibiting AChE
      and NTE overlapped for neuropathy-causing OPs. For example, apparent IC50 values
      for NTE inhibition were less than 9.6-fold the apparent IC50 values for AChE
      inhibition when cells were exposed to the neuropathy-inducing OPs diisopropyl
      phosphorofluoridate, cyclic tolyl saligenin phosphate, phenyl saligenin
      phosphate, mipafox, dibutyl dichlorovinyl phosphate, and di-octyl-dichlorovinyl
      phosphate. In all cases, esterase inhibition occurred at lower concentrations
      than those needed for cytoxicity. These results suggest that either mouse or
      human neuroblastoma cell lines can be considered useful in vitro models to
      distinguish esterase-inhibiting OP neurotoxicants.

PMID- 9268606
TI  - Effect of piperonyl butoxide on cell replication and xenobiotic metabolism in the
      livers of CD-1 mice and F344 rats.
AB  - Male CD- 1 mice were fed diets containing 0 (control), 10, 30, 100, and 300
      mg/kg/day piperonyl butoxide (PBO) and 0.05% sodium phenobarbital (NaPB) and male
      F344 rats were fed diets containing 0 (control), 100, 550, 1050, and 1850
      mg/kg/day PBO and 0.5% NaPB for periods of 7 and 42 days. In both species PBO and
      NaPB increased relative liver weight and whereas PBO produced a midzonal (mouse)
      or periportal/midzonal (rat) hypertrophy, NaPB produced a centrilobular
      hypertrophy. In the rat, individual cell necrosis was also observed at 42 days
      after high doses of PBO. Replicative DNA synthesis, assessed as the hepatocyte
      labeling index following implantation of 7-day osmotic pumps containing 5-bromo
      2'-deoxyuridine during Study Days 0-7 and 35-42, was increased in mice given 300
      mg/kg/day PBO and NaPB for 7 days and in rats given 550 and 1050 mg/kg/day PBO
      and NaPB for 7 days and 1050 mg/kg/day PBO for 42 days. While PBO had no effect
      on body weights in mice, the body weights of rats given 550, 1050, and 1850
      mg/kg/day PBO for 42 days were reduced to 92, 89, and 70% of control,
      respectively. PBO induced microsomal cytochrome P450 content and mixed function
      oxidase activities in the mouse and rat, although the effects were less marked
      than those produced by NaPB. In summary, this data demonstrates that PBO can
      produce liver enlargement in the mouse and the rat which is associated with
      induction of xenobiotic metabolism, hypertrophy, and hyperplasia. The hepatic
      effects of PBO in the mouse were similar to but less marked than those produced
      by NaPB. In the rat high doses of PBO were hepatotoxic and resulted in a marked
      reduction in body weight. Thus while the reported formation of eosinophilic
      nodules in mouse liver by PBO may occur by a mechanism(s) similar to that of NaPB
      and other nongenotoxic enzyme inducers, the reported tumor formation in rats at
      greater than the maximum tolerated dose is most likely associated with marked
      enzyme induction in conjunction with a regenerative hyperplasia resulting from
      PBO-induced hepatotoxicity.

PMID- 9268607
TI  - 4-Aminopyridine reverses saxitoxin (STX)- and tetrodotoxin (TTX)-induced
      cardiorespiratory depression in chronically instrumented guinea pigs.
AB  - The extent to which cardiorespiratory infirmity and other sublethal effects of
      saxitoxin (STX) and tetrodotoxin (TTX) can be reversed by 4-aminopyridine (4-AP)
      was investigated in guinea pigs chronically instrumented for the concurrent
      electrophysiological recordings of electrocorticogram (ECoG), diaphragmatic
      electromyogram (DEMG), Lead II electrocardiogram, and neck skeletal muscle
      electromyogram. Animals were intoxicated with either STX or TTX (2 and 3
      microg/kg, im) to produce a state of progressive cardiorespiratory depression
      (depicted by decreasing DEMG amplitude, bradypnea, and bradycardia). At the point
      where cardiorespiratory performance was most seriously compromised (approximately
      30 min posttoxin), 4-AP (1 or 2 mg/kg, im) was administered. The therapeutic
      effect of 4-AP was striking in that, within minutes, the toxin-induced
      diaphragmatic blockade, bradypnea, bradycardia, and depressed cortical activity
      were all restored to a level either comparable to, or surpassing, that of
      control. The optimal 4-AP dose level was determined to be 2 mg/kg (im) based on
      analyses of cardiorespiratory activity profiles throughout the course of
      intoxication and 4-AP treatment. At the dose levels (either 1 or 2 mg/kg) used to
      restore ventilatory function and cardiovascular performance, 4-AP produced no
      sign of seizures and convulsions. Although less serious secondary effects such as
      cortical excitant/arousal effect (indicated by ECoG power spectral analysis) and
      transient periods of skeletal muscle fasciculation were observed, these events
      were of minor concern particularly in view of the remarkable therapeutic effects
      of 4-AP.

PMID- 9268608
TI  - Kinetic and safety studies on intrathecally infused recombinant-methionyl human
      brain-derived neurotrophic factor in dogs.
AB  - To define the kinetics and safety of spinally infused recombinant-methionyl human
      brain-derived neurotrophic factor (r-metHuBDNF), beagle dogs were prepared with
      lumbar intrathecal catheters passed through the cisternal membrane to the L1-L4
      lumbar level. For kinetic studies, r-metHuBDNF was delivered by bolus or infusion
      through one catheter and lumbar CSF was sampled periodically through a second. As
      a lumbar bolus, r-metHuBDNF displayed a biphasic clearance with t(1/2)a = 0.7 hr
      and t(1/2)b = 7. 9 hr. Lumbar to cisternal concentrations after bolus delivery
      were approximately 60:1. For safety studies, dogs received continuous intrathecal
      infusion (2.4 ml/day) for 28 days of saline (n = 6), r-metHuBDNF at 200 (n = 6),
      800 (n = 6), or 2000 (n = 7) microg/day. Control dogs showed no changes.
      Intrathecally infused r-metHuBDNF produced a dose-dependent increase in muscle
      tone and decreased coordination. Low-dose r-metHuBDNF was associated with
      moderate increases in muscle tone after 22-28 days of infusion. No clinically
      important changes were noted in rectal temperature, arterial pressure,
      respiration and heart rate, body weight, food consumption, stool or urine output,
      or change in blood chemistries measured throughout the study. Cisternal CSF
      protein and glucose sampled at 28 days were not different between dose groups and
      all cultures were negative. Histopathological examination of the spinal cord
      typically revealed some degree of chronic inflammation around the catheter,
      including fibrotic adhesions and focal accumulations of lymphoid and plasma
      cells, but these effects were not dose dependent. In other dogs receiving r
      metHuBDNF (2000 or 4000 microg/day), termination of infusion resulted in
      significant recovery.

PMID- 9268609
TI  - The ototoxicity of trichloroethylene: extrapolation and relevance of high
      concentration, short-duration animal exposure data.
AB  - Inhalation exposure to high concentrations of 1,1, 2-trichloroethylene (TCE) has
      been shown to damage hearing in the mid-frequency range in the rat. The present
      study directly evaluated the adequacy of high-concentration, short-term exposures
      to TCE for predicting the neurotoxicity produced by longer duration exposures.
      Adult male Long-Evans rats (n = 10-12 per group) were exposed to TCE via
      inhalation (whole body) in 1-m3 stainless steel flow-through chambers for 6
      hr/day, 5 days/week. The following exposures were used: 1 day (4000-8000 ppm), 1
      week (1000-4000 ppm), 4 weeks (800-3200 ppm), and 13 weeks (800-3200 ppm). Air
      only exposed animals served as controls. Auditory thresholds were determined for
      a 16-kHz tone 3-5 weeks after exposure using reflex modification audiometry.
      Results replicated previous findings of a hearing loss at 16 kHz for all exposure
      durations. The dB15 concentrations (concentration that increases thresholds by 15
      dB) for 16-kHz thresholds were 6218, 2992, 2592, and 2160 ppm for the 1-day, 1
      week, 4-week and 13-week exposures, respectively. These data demonstrate that the
      ototoxicity of TCE was less than that predicted by a strict concentration x time
      relationship. These data also demonstrate that simple models of extrapolation
      (i.e., C x t = k, Haber's Law) overestimate the potency of TCE when extrapolating
      from short-duration to longer-duration exposures. Furthermore, these data suggest
      that, relative to ambient or occupational exposures, the ototoxicity of TCE in
      the rat is a high-concentration effect.

PMID- 9268610
TI  - Localization of IGF-I and IGF-I receptor mRNA in Sparus aurata larvae.
AB  - Studies of the ontogeny of IGF-I mRNA during embryonic and larval development of
      the gilthead sea bream Sparus aurata showed its expression during these early
      developmental stages. The present study applies in situ hybridization to localize
      IGF-I and IGF receptor mRNAs in 16-day larvae of S. aurata. Paraffin sections
      were hybridized with homologous RNA probes labeled by [35S]UTP. IGF-I mRNA
      expression was found mainly in chondrocytes, in both the gill arches and cranial
      cartilage, in skeletal muscle, in the brain, in the pancreas, in the retina, and
      in the epithelial cells surrounding the lens. A strong positive reaction for IGF
      receptor mRNA was found in skeletal muscle, in the pancreas, and in the lymphoid
      tissue found in the intertubular tissue of the kidney. Signals were less intense
      in brain and chondrocytes. It is suggested that in teleosts, as in higher
      vertebrates, IGF-I may be involved in the regulation of tissue growth and
      differentiation in an autocrine/paracrine manner.

PMID- 9268611
TI  - A novel and simple technique for ectopic transplantation of the pituitary gland.
AB  - Sites for ectopic transplantation of the pituitary include the kidney capsule of
      mammals, the anterior eye chamber, the so-called hypophysiotropic area of the
      brain, the third cerebral ventricle, and the tail of the amphibian tadpole.
      Transplantation of pituitary in the kidney capsule of mammals is a simple
      technical procedure but most nonmammalian species do not offer such a convenient
      site. Transplantation of pituitaries at other ectopic sites involves technical
      sophistication and cannot be undertaken by all investigators, and retrieving the
      transplant is often difficult. A new technique is described to overcome these
      difficulties. Silastic tube pieces (7-10 mm) were ligated at both ends and cut
      longitudinally, and pituitaries taken from sister animals (homologous donors)
      were inserted through the incision. The Silastic tubes were then implanted either
      in the abdominal cavity or in the liver of rat, Japanese quail, and toad. They
      were retrieved after 7 or 14 days (in the case of rat and Japanese quail) or
      after 10 or 20 days (in the case of toad), and the pituitary was sectioned and
      stained immunocytochemically using rat and human prolactin (PRL) antisera. Taking
      the preponderance of PRL cells in the pars distalis as a parameter for
      determining the viability and functional status of the transplants (because
      ectopically transplanted pituitaries secrete abundant PRL), it was found that 13
      of 16 pituitary homografts had been well established and there was no visible
      host-graft incompatibility. The technique reported is novel and simple, and it
      ensures quick delivery of the grafts and their easy retrieval without any loss
      whatsoever. It is expected that the technique would be very useful and would find
      wider application because it can also be employed for transplanting other
      organs/tissues into a wide range of animals, including invertebrates.

PMID- 9268612
TI  - Ultrastructural and immunocytochemical studies of prolactin-secreting cells in
      adenohypophysis of the mink (Mustela vison).
AB  - This investigation aimed to identify, by the double immunogold procedure, the
      ultrastructural characteristics of prolactin (PRL) cells in the mink. Such cells
      showed a marked pleomorphism and had a close topographic relationship with growth
      hormone cells. A common morphological characteristic of PRL cells in all stages
      of mink development was the presence of round secretory granules, in contrast to
      changes in the ultrastructural characteristics of PRL cells with physiological
      state and photoperiod. Thus PRL cells in prepubertal, pubertal, and sexually
      inactive adult mink, killed under a short-day photoperiod, showed little
      development of the organelles but a significantly increased cytoplasmic electron
      density. In sexually active mink and in lactating females under long-day
      conditions, PRL cells had a highly developed cytoplasmic organelle structure
      consisting mainly of rough endoplasmic reticulum. The morphometric study
      demonstrated that the mean diameter of the secretory granules similarly varied in
      both sexes. Pubertal mink had PRL cells with smaller secretory granules (female
      74.1 +/- 0.6 nm, male 80.4 +/- 1.7 nm), whereas adult mink killed under a long
      day photoperiod presented PRL cells with larger secretory granules (female 194.5
      +/- 2.2 nm, male 203.3 +/- 1.7 nm). The changes in the ultrastructural
      characteristics of PRL cells during the annual cycle suggest a photoperiodic
      influence upon these cells. In addition the heterogeneity in ultrastructural
      characteristics and storage characteristics of PRL in some adult mink may suggest
      a varying metabolic role for PRL under certain, as yet not fully characterized,
      conditions.

PMID- 9268613
TI  - Interaction of osmotic and volemic mechanisms in secretion of atrial and
      ventricular natriuretic peptides in eels.
AB  - In eels, plasma osmolality rather than blood volume is a major regulator of
      atrial and ventricular natriuretic peptide (ANP and VNP) secretion. The present
      study examined the effects of changes in blood volume on ANP and VNP secretion
      stimulated by an increase in plasma osmolality in freshwater-adapted eels. Basal
      plasma ANP and VNP levels were decreased by 2 ml of blood withdrawal (28% of
      total blood volume), but not changed by blood volume expansion with 2 ml of 0.9%
      NaCl solution containing 2% dextran. The blood loss suppressed the increased
      plasma ANP level caused by an injection of 2.5 ml/kg of 1.7 M NaCl solution at 60
      min (120.5 +/- 31.0 fmol/ml, n = 5) compared with controls without blood volume
      manipulation (586. 6 +/- 43.6 fmol/ml, n = 5), but the plasma ANP level
      transiently increased in bled fish immediately after osmotic stimulus, probably
      due to the release of ANP stored in the cardiac tissues after the blood loss.
      Changes in plasma VNP were not so evident as those of ANP. In contrast, blood
      volume expansion augmented the increase in plasma ANP and VNP levels within 60
      min after osmotic stimulus compared with controls. The recovery of plasma VNP
      level was quicker than that of plasma ANP. Increases in plasma Na, Cl
      concentrations, and osmolality were not different among hypovolemic,
      normovolemic, and hypervolemic eels after osmotic stimulation. It is concluded
      that volume itself is a minor regulator for ANP and VNP secretion compared with
      osmotic stimulus, but it plays a modulatory role in osmotically induced ANP and
      VNP secretion in eels.

PMID- 9268614
TI  - The effect of photoperiod and food intake on daily changes in plasma calcitonin
      in broiler breeder hens.
AB  - The roles of photoperiod, energy balance, and concentrations of plasma total
      calcium (CaT) on daily changes in plasma calcitonin (CT) were investigated in
      broiler breeder hens (84-100 weeks old). In the first study, broiler breeder hens
      (n = 24), reared on 14L:10D, were divided into two groups. One group was
      transferred from a restricted diet (DR) of 150 g/day to ad libitum (AL) for 14
      days, while the other group remained on DR. After 2 weeks of ad libitum feeding,
      birds from each group (AL and DR) were bled every 2 hr for 24 hr for measurement
      of plasma CaT and CT. In a second study, the hens (n = 20) were transferred to
      continuous light (LL) for 30 days. After the 30 days, food was removed from one
      group for 48 hr prior to blood sampling for 24 hr at 3-hr intervals. In a third
      study, birds were transferred to an ahemeral light cycle (11L:10D) for 28 days.
      Food was removed from the birds (n = 11) for 48 hr prior to blood sampling every
      3 hr for 24 hr. Four weeks later the same birds were bled again for 24 hr, but
      this time the birds were maintained on a restricted feeding schedule. Plasma CT
      was measured by a specific heterologous electrochemiluminescent (ECL) assay while
      plasma CaT was measured by atomic absorption. The results showed that plasma CT
      concentrations did not correlate with plasma CaT concentrations. Comparisons made
      between initial and final CaT and CT concentrations indicated an effect of stress
      due to repeated handling of the birds. Concentrations of plasma CT were
      significantly reduced in the fasted animals (P < 0.05) compared to diet
      restricted controls. There was a significant increase in plasma CT during the
      dark period of fed animals which was abolished in animals maintained on LL or
      fasted. In conclusion, a surge in plasma CT requires that the hens be provided
      food and that they be exposed to a dark cycle.

PMID- 9268615
TI  - Expression of MCH and POMC genes in rainbow trout (Oncorhynchus mykiss) during
      ontogeny and in response to early physiological challenges.
AB  - The expression of the neuropeptide melanin-concentrating hormone (MCH) in two
      groups of hypothalamic neurones (NLT- and LVR-MCH neurones), and POMC in the
      pituitary corticotropes and melanotropes, has been examined in rainbow trout
      larvae using immunocytochemistry and quantitative in situ hybridization. The aim
      was to establish at what stage in ontogeny these cells first respond to two
      physiological challenges-background color and stress. Trout reared in black or
      white trays showed adaptive skin pigmentary changes at 10 days posthatching, when
      fish in a pale environment abruptly exhibited melanin aggregation from a prior
      dispersed state, although the pigment cells were already competent to respond to
      adrenalin and MCH in vitro at 3 days. Immunoreactive MCH was detectable in the
      neurohypophysis at hatching and MCH mRNA in the NLT-MCH neurones (which project
      to the pituitary) was enhanced at 7 days in the white-reared trout.
      Immunostainable POMC was also present in the pars intermedia at hatching but
      their POMC mRNA was unaffected by tank color until 28 days, when it was enhanced
      in the black-reared trout. It is suggested that early pigment concentration
      depends on neural signals from the sympathetic nervous system in conjunction with
      MCH from the NLT rather than on a reduction in alphaMSH secretion from the pars
      intermedia. MCH mRNA in the LVR-MCH neurones was increased on a pale environment
      only 28 days after hatching, suggesting that these cells play little role in the
      early adaptive pigment response. Previous studies on the ontogeny of cortisol
      secretion indicate the hypothalamopituitary-interrenal axis can respond to stress
      by about 14 days. However, the pituitary ACTH cells showed no stress-induced
      changes in POMC mRNA until 28 days. ACTH release may therefore be dissociated
      from POMC transcription in the early stages of development. The LVR- and NLT-MCH
      neurones were both stimulated by stress, LVR-MCH mRNA responding by 14 days and
      NLT-MCH mRNA by 21 days. Melanotrope POMC mRNA was reduced by stress but the
      physiological significance of this is not known.

PMID- 9268616
TI  - Coexistence of alpha1 and beta adrenergic receptors in the liver of the frog Rana
      esculenta, the toad Bufo bufo, the lizard Podarcis sicula campestris, and the
      turtle Pseudemys picta elegans.
AB  - In mammals and birds the characteristics of alpha1 adrenergic receptors and their
      biological role in liver metabolism have been clearly described, although the
      predominance of receptor subtypes varies with species. In contrast, the actual
      presence of hepatic alpha1 adrenergic receptors in fish, amphibians, and reptiles
      has been questioned. Only recently has their existence been demonstrated in some
      fish species and also in the wood frog Rana sylvatica. The present study assessed
      the presence of alpha1 adrenergic binding sites on hepatic membranes of frogs,
      toads, lizards, and turtles using the specific alpha1 adrenergic receptor
      antagonist [3H]prazosin; for comparison, the binding of the specific beta
      adrenergic receptor antagonist [3H]CGP-12177A was evaluated in the same
      preparations. alpha1 Adrenergic receptors are indeed present in the liver of the
      ectotherms examined. Specific binding is saturable, reversible, and linear as a
      function of tissue concentration. The binding data indicated the presence of two
      classes of binding sites displaying high and low affinities with Kds in the
      nanomolar and micromolar ranges, respectively. The present study provides the
      first evidence for the presence of alpha1 adrenergic receptors in the liver of
      toad, lizard, and turtle while confirming their existence in another species of
      frog, Rana esculenta.

PMID- 9268617
TI  - Seasonal changes in gonadal activity and the effects of stress on reproductive
      hormones in the common snapping turtle, Chelydra serpentina.
AB  - The seasonal gonadal cycle (including gonadal histology, sex steroids, and
      gonadotropins) was studied in freshly captured common snapping turtles, Chelydra
      serpentina, from Wisconsin, and the effects of capture stress were evaluated. The
      ovarian and testicular cycles are shorter than those reported in other freshwater
      turtles; the cycles commence in mid-May and terminate in early September,
      immediately after the completion of gonadal growth and maturation. In the female,
      testosterone (T), 17beta-estradiol (E2), and progesterone (Pro) were highly
      correlated with follicular growth and vitellogenesis. Ovulation in captivity and
      under natural conditions occurred after mid-May. In captivity, ovulation was a
      rapid process (24-48 hr); as the follicles descended into the uterine horns there
      was a significant increase in E2 and Pro and eggs were retained in the uterine
      horns for about 2 weeks before oviposition. In the male, T was significantly
      correlated with testicular growth and spermiation. Follicle-stimulating hormone
      (FSH) reached significantly higher levels (P < 0.01) in males (8.99 +/- 0.38
      ng/ml) than in females (2.66 +/- 0.22 ng/ml), but luteinizing hormone was
      undetectable in both sexes. FSH was not correlated with the steroids in either
      sex. Sex steroids and FSH began to rise before spermiation and vitellogenesis and
      remained elevated until completion of gonadal growth and maturation. Leydig
      cells, the main source of plasma androgen in this species, became active shortly
      after emergence from hibernation and remained steroidogenically active for the
      rest of the cycle. Sertoli cells became active only after spermatogenesis was
      under way but also stayed active for the rest of the summer. Courtship and mating
      behaviors were observed in spring, summer, and fall. The snapping turtle is
      strictly aquatic with no basking behavior and limited behavioral thermoregulation
      so there is little daily fluctuation in body temperature. Environmental
      correlates indicate that the snapping turtle is temperature dependent:
      recrudesence occurs with a slight increase in water temperature during spring and
      early summer, while a dramatic drop in gonadal activity accompanies a slight
      decrease in temperature in fall. Changes in temperature may underlie changes in
      gonadal activity in the face of relatively stable FSH. Male turtles subjected to
      captivity and periodic blood sampling show a significant decline in T. The
      hormonal levels continued to decline whether the turtles are exposed to optimum
      or extreme temperatures. However, there is more rapid decline in T values in
      animals with regressed testes (June) than in those with well-developed testes
      (July). Male and female turtles kept in captivity at different phases of the
      cycle exhibit different patterns and degrees of response to stress, possibly
      related to the hormonal levels and the condition of the gonads.

PMID- 9268618
TI  - Correlation among thermosensitive period, estradiol response, and gonad
      differentiation in the sea turtle Lepidochelys olivacea.
AB  - Reptile embryos with temperature sex determination have a thermosensitive period
      (TSP). The finding that exogenous estradiol (E2) overcomes the effect of male
      promoting temperature led to the idea that temperature may regulate estrogen
      concentration in the gonad during TSP. Since interspecific variations in TSP and
      in the effect of exogenous E2 exist, we undertook a study in the olive ridley
      Lepidochelys olivacea. Four parameters were correlated: the TSP (time dimension),
      the thermosensitive stages (rate of development), gonad development (histological
      aspect), and the estradiol response. Two kinds of experiments were performed: (1)
      Eggs were shifted once, at different stages of development, from a male-promoting
      temperature to a female-temperature (or vice versa) for the remainder of
      development. (2) Eggs at male-promoting temperature were treated once with 6 or
      12 microg of estradiol (E2) at various times of incubation. Sex ratio was
      established around hatching in each experimental series. We found that the
      temporal dimension of the TSP was around 7 days (Days 20-27 of incubation) at a
      male-promoting or a female-promoting temperature. The rate of development of the
      whole embryo and gonadal growth was faster at female-promoting temperature than
      at male-promoting temperature. Formation of the genital ridge began at stage 21
      22 and histological differentiation of the gonads occurred around stage 26-27.
      Although these stages coincided with the TSP, at male-promoting temperature the
      thermosensitive stages occurred earlier (from stages 20-21 to stages 23-24) than
      at female-promoting temperature (from stages 23-24 to stages 26-27). Thus, at
      male promoting-temperature, sex was determined in embryos with incipient or
      undifferentiated gonads. In contrast, E2 treatment continued to feminize the
      gonads of embryos at a male-promoting temperature beyond the TSP up to stage 25
      26, but the E2-induced ovaries were significantly smaller than temperature
      induced ovaries. It is suggested that the doses of E2 used were higher than the
      concentration of endogenous E2 required for normal sex determination. The lack of
      correlation between sex determination and gonad differentiation suggests that
      irreversible molecular processes underlying sex determination occur earlier at
      male- than at female-promoting temperature. Results suggest that the male sex may
      be the default state and that the female condition must be imposed upon it.

PMID- 9268619
TI  - Expression and regulation of mRNA for inhibin/activin alpha- and betaA-subunits
      in the granulosa layer of the two largest preovulatory follicles during the hen
      ovulatory cycle.
AB  - In order to understand the role of inhibin and activin in regulating follicular
      development in the hen, the steady-state mRNA levels of inhibin/activin alpha-
      and betaA-subunits in the granulosa layer of the largest (F1) and second largest
      (F2) follicles of the hen were investigated at 4-hr intervals throughout the
      ovulatory cycle. In addition, because it was hypothesized that luteinizing
      hormone (LH) regulated betaA-subunit expression, the effect of in vivo
      administration of ovine LH (oLH) on the expression of these subunits during the
      early- and mid-ovulatory cycle was examined. Northern blot analysis, using 32P
      labeled cDNA probes of chicken inhibin/activin alpha- and betaA-subunits and
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH, internal control), revealed that
      in the F1 follicle, the relative level of betaA-mRNA (n = 3) was low at 23.5 hr
      and increased (P < 0.05) at 19.5, 15.5, and 11.5 hr before the next predicted
      ovulation. It then decreased (P < 0.05) at 7.5 hr and was further reduced at 3.5
      and 0.5 hr prior to ovulation. In the F2 follicle, betaA-mRNA was maintained at a
      basal level throughout the sampling period except for a brief increase (P < 0.05)
      at 0.5 hr before ovulation. In contrast to the betaA-subunit, inhibin alpha-mRNA
      was abundantly expressed with no significant variations throughout the ovulatory
      cycle in either the F1 or the F2 follicle. When oLH was injected at 18 hr before
      ovulation, 200 but not 100 or 50 microg/kg (n = 3 hens per dose) significantly (P
      < 0.05) reduced the betaA-mRNA level in the F1 follicle by 2 hr after injection
      compared to the control (saline). The experiment was repeated at 12 hr before
      ovulation and both 100 and 200 but not 50 microg/kg oLH significantly (P < 0.05)
      reduced the expression of betaA-subunit mRNA with no significant difference
      between 100 and 200 microg/kg oLH. In contrast to the betaA-subunit, inhibin
      alpha-subunit mRNA was abundantly expressed and not affected by oLH treatment.
      Our data indicate that the expression of inhibin/activin betaA- but not alpha
      subunit mRNA is developmentally regulated in the granulosa layer of the two
      largest follicles during the hen ovulatory cycle. In addition, LH may
      participate, directly or indirectly, in negative regulation of the betaA-subunit.

PMID- 9268620
TI  - Number of mast cells in the Harderian gland of the lizard Podarcis sicula sicula
      (Raf): the annual cycle and its relation to environmental factors and estradiol
      administration.
AB  - The Harderian gland of the lizard Podarcis sicula sicula (Raf) contains
      connective tissue type mast cells whose numbers vary during the year showing two
      peaks, one in spring the other in winter. No sex differences are found throughout
      the year. Thermal and photoperiodic manipulations indicate that only temperature
      influences mast cell number (MCN) both in winter and in summer but not in spring.
      In animals exposed to high temperatures in February (but not in May) MCN
      declined, while exposure to low temperature in July had the opposite effect.
      Estradiol treatment of the February and April lizards increased MCN, an effect
      counteracted by the synthetic antiestrogen tamoxifen; in July lizards, this did
      not occur. In animals exposed to a high temperature in February, estradiol had no
      effect, as in animals exposed to low temperatures in July. These data suggest
      that in spring MCN seems to be more responsive to hormonal stimuli rather than
      external cues (temperature), while in summer MCN is more sensitive to temperature
      than to hormonal stimuli (estradiol). Both humoral and external factors are
      concluded to influence mast cell numbers in the Harderian gland of the lizard P.
      sicula sicula.

PMID- 9268621
TI  - Deciphering posttranslational processing events in the pituitary of a
      neopterygian fish: cloning of a gar proopiomelanocortin cDNA.
AB  - A cDNA that codes for the polypeptide hormone precursor proopiomelanocortin
      (POMC) was cloned and sequenced from a gar (Lepisosteus osseus) pituitary cDNA
      library. The gar POMC cDNA is 1237 bp and contains a 780-bp open reading frame.
      The deduced amino acid sequence for gar POMC is 259 amino acids in length. The
      general organization of gar POMC is very similar to that of other gnathostome
      POMC sequences. The beta-endorphin sequence had 91% sequence identity with
      sockeye A beta-endorphin and 71% sequence identity with Xenopus laevis beta
      endorphin. Three melanocyte-stimulating hormone (MSH) core sequences [HFR(W)]
      were detected. The gar alpha-MSH sequence was identical to the alpha-MSH sequence
      in rat POMC. The gar beta-MSH sequence had 77% sequence identity with salmonid
      forms of beta-MSH and 53% sequence identity with tetrapod forms of beta-MSH. The
      gamma-MSH region of gar POMC only had 26% primary sequence identity with tetrapod
      gamma-MSH sequences. Gar gamma-MSH had an incomplete MSH core sequence (HRF), an
      apparent internal deletion of five amino acids, and lacked flanking paired basic
      amino acids essential for proteolytic cleavage. The apparent degenerate nature of
      gar gamma-MSH is discussed in light of the absence of this sequence in salmonid
      fish.

PMID- 9268622
TI  - Serum concentrations of steroid hormones in the mature male bonnethead shark,
      Sphyrna tiburo.
AB  - The male bonnethead shark, Sphyrna tiburo, undergoes an annual cycle of
      spermatogenesis and testicular regression and recrudescence. In southwestern
      Florida populations, testicular development and spermatogenesis begin in late
      spring and peak in late summer, with mating not taking place until about 2 months
      after the peak. Steroid hormones, some of which are known to play influential,
      essential roles in spermatogenesis, were measured in the serum during a full
      annual cycle in mature males from a wild population. Serum 17beta-estradiol (E2),
      progesterone (P4), testosterone (T), and dihydrotestosterone (DHT) concentrations
      were determined by radioimmunoassay. Serum T, DHT, and P4 concentrations followed
      the pattern of testicular development and regression, with all three steroid
      hormones attaining the highest significant levels (P < 0. 001) in late summer and
      falling to the lowest levels in mid-winter. Serum E2 concentrations showed
      significant changes (P < 0.01) with a peak in early spring. Male bonnethead
      sharks had significantly lower concentrations of E2 (P < 0.001) and significantly
      higher concentrations of T, DHT (P < 0.001), and P4 (P < 0.05) than those
      published for females. When steroid concentrations were compared to a behavioral
      rating of stress, only P4 showed a significant correlation to the stress behavior
      (P = 0.0447), but the significance was much lower than the significant
      correlation of P4 by month (P < 0.001).

PMID- 9268623
TI  - Primary structure of insulin from the african lungfish, Protopterus annectens.
AB  - Among the extant Sarcopterygii, the interrelationship between the Dipnoi
      (lungfishes), Actinistia (coelacanths), and Tetrapoda (tetrapods) is
      controversial. Insulin has been purified from an extract of the pancreas of the
      African lungfish Protopterus annectens and its primary structure established as A
      chain, Gly-Ile-Val-Glu-Gln-Cys-Cys-His-Lys-Pro10-Cys-Ser-Leu- Tyr -Glu-Leu-Glu
      Asn-Tyr-Cys20-Asn-Val-Pro; and B-chain, Ala-Val-Leu-Asn-Gln-His-Leu-Cys-Gly-Ser10
      His-Leu-Val- Glu- Ala-Leu-Tyr-Leu-Val-Cys20-Ala-Asp-Asn-Gly-Phe- Phe-Tyr-Lys-Pro
      Ser30-Gly. Lungfish insulin contains unusual structural features, such as the
      dipeptide extension to the C-terminus of the A-chain and the substitution Arg -->
      Asn at position B-23 in the putative receptor binding region of insulin, which
      may be expected to influence appreciably its biological potency relative to
      mammalian insulins. Lungfish insulin also contains amino acid substitutions such
      as Gly --> Ala at position B-21, Glu --> Asp at position B-22, and a Lys --> Ser
      residue at position B-30, previously found in insulins from amphibia. This
      observation is consistent with paleontological data suggesting that lungfish and
      amphibia share a close phylogenetic relationship.

PMID- 9268625
TI  - Effects of testosterone and cortisol on the renal morphology of male Antechinus
      stuartii (Marsupialia).
AB  - The life cycle of the marsupial Antechinus stuartii includes postmating mortality
      of all males. A previous study found that renal morphology changes during the
      yearly cycle when endogenous concentrations of testosterone and cortisol are
      elevated in males. The present study determined whether administration of
      testosterone only, cortisol only, or testosterone plus cortisol affects renal
      structure in males at a time of year when endogenous hormones are low (May).
      Saline administration was used as the control. Gross morphometrics of the kidney
      did not show significant differences between groups. However, some pathological
      changes were observed in distal tubules and collecting ducts from cortisol
      treated groups, and in the glomeruli of testosterone-treated males. Hypertrophy
      of the proximal tubules, distal straight tubules, and the cells of the cortical
      collecting duct occurred with the administration of testosterone. Distension of
      the distal convoluted tubules, cortical collecting ducts, and outer medullary
      collecting ducts occurred with the administration of cortisol, and there was some
      interaction with testosterone. Glomerular volumes increased with cortisol
      administration, although cortisol interacted with testosterone in the superficial
      glomeruli. Many of these changes mimicked those seen in the seasonal study, with
      the kidneys of the testosterone plus cortisol group closely resembling those of
      males in August, just prior to male mortality. The present study demonstrates
      that testosterone administration causes hypertrophy of renal tissue, whereas
      cortisol administration can cause tubular disruption in male A. stuartii.

PMID- 9268624
TI  - Photorefractoriness in European starlings (Sturnus vulgaris) is not dependent
      upon the long-day-induced rise in plasma thyroxine.
AB  - Transfer of intact, photosensitive starlings from short to long days causes an
      increase in plasma thyroxine and gonadal maturation and later induces
      photorefractoriness. Thyroidectomy of starlings prevents the induction of
      photorefractoriness. This study investigated whether the long-day-induced
      increase in plasma thyroxine is necessary for the induction of
      photorefractoriness. Photosensitive starlings were thyroidectomised, given
      thyroxine in their drinking water at concentrations that result in plasma
      thyroxine at short-day physiological concentrations or lower, and transferred to
      long days. Plasma thyroxine and prolactin, gonadal size, and moult were
      monitored. The group with short-day concentrations of plasma thyroxine became
      photorefractory at the same time as intact controls transferred to long days. The
      other groups, with lower plasma thyroxine, also became photorefractory, but the
      onset of photorefractoriness was delayed. The increase in plasma prolactin
      following photostimulation was proportional to plasma thyroxine concentrations.
      The onset of moult was also related to plasma thyroxine. We conclude that the
      long-day concentrations of plasma thyroxine observed in the plasma of intact
      starlings are not necessary for the induction of photorefractoriness. This
      suggests that thyroxine acts as a permissive factor rather than actively driving
      the photorefractory process.

PMID- 9268626
TI  - Progesterone in Periplaneta americana and Neobellieria bullata adults from the
      procuticle phase until first progeny production.
AB  - A significant amount of progesterone-like immunoreactive material (150 ng/g) was
      measured by EIA in the procuticle phase of adult of both sexes of Periplaneta
      americana. This peak markedly decreased to 1-10 ng/g during sclerotization and
      was unlikely to be of dietary origin. In the case of 0-hr-old P. americana adults
      96-98% of progesterone-like material was localized in the digestive tract and
      Malpighian tubules. In contrast, a relatively low level of progesterone-like
      immunoreactive material was measured in 0-hr-old Neobellieria bullata adults.
      Activity of 3beta-HSD/isomerase converting pregnenolone to progesterone was high
      (22-43 fmol/mg protein/20 min) in 0-hr-old P. americana adults and significantly
      fell during sclerotization. High progesterone levels (13-16 ng/g), measured by
      HPLC-RIA, coexist with high levels of 3beta-HSD/isomerase activity. Orally active
      human contraceptives (ethisterone, ethynodiol, ethynodiol diacetate, lynestrenol,
      mestranol, norgestrel, norethynodrel, tamoxifen citrate, and mifepristone) which
      act on mammalian steroid receptors had no significant effects on progeny
      production in either polytrophic or meroistic insect ovaries even at
      concentration of 5000 mg/kg.

PMID- 9268627
TI  - Obesity QTLs on mouse chromosomes 2 and 17.
AB  - The inheritance of obesity has been analyzed in an intercross between the mouse
      strains AKR/J and C57L/J. Two novel obesity quantitative trait loci (QTLs) have
      been identified using the strategy of selective DNA pooling. One QTL affecting
      adiposity, Obq3, was mapped to a 39-cM segment near the middle of Chromosome 2,
      with a peak lod score (5.1) just distal to the D2Mit15 locus. The AKR/J Obq3
      allele confers increased adiposity in a nearly additive manner, and males are
      more affected than females. A second obesity QTL (Obq4) maps to the centromeric
      end of Chromosome 17, with a lod score peak of 4.6 at D17Mit143. The obesity
      conferring allele is contributed by C57L/J and acts in a recessive or an additive
      manner. Obq4 also has more influence in males and affects the inguinal fat depot
      differentially. Obq3 and Obq4 account for 7.0 and 6.1% of the phenotypic variance
      in adiposity (gender-merged data), respectively. The possible relationships
      between these QTLs and previously described obesity QTLs and candidate genes are
      discussed. The large number of different obesity QTLs that have been described in
      mice and the relatively small effects contributed by individual loci suggest
      considerable genetic complexity.

PMID- 9268628
TI  - Estimating physical distances from radiation hybrid mapping data.
AB  - Radiation hybrid mapping has become an established tool for building physical
      maps. It represents a powerful way of constructing YAC contigs and high
      resolution maps for positional cloning experiments. Ideally, radiation hybrids
      should not only provide support for the true order of the markers, but also
      accurate estimates of the physical distances between them. Statistical analysis
      of radiation hybrids has proved difficult because of the number of parameters
      (representing the fragment retention probabilities) that must be estimated, and
      simplifying assumptions are needed to analyze large numbers of markers
      simultaneously. The ramifications of these assumptions for the calculation of
      physical distances are investigated. A simple two-locus model is presented to
      demonstrate that variation in marker retention can lead to distortions in the
      estimates of distance. Multilocus simulations show that, when marker retention is
      constant across the chromosome, good estimates of physical distance can be
      derived using simple models of retention. However, further simulations exploring
      variable retention schemes demonstrate that significant errors in the estimates
      of map distances can occur. Ways of minimizing these distortions are discussed.

PMID- 9268629
TI  - Isolation and characterization of a gene from the DiGeorge chromosomal region
      homologous to the mouse Tbx1 gene.
AB  - DiGeorge syndrome, velocardiofacial syndrome, conotruncal anomaly face syndrome,
      and isolated and familial forms of conotruncal cardiac defects have been
      associated with deletions of chromosomal region 22q11.2. This report describes
      the identification, cloning, and characterization of the human TBX1 gene, which
      maps to the center of the DiGeorge chromosomal region. Further, we have extended
      the mouse cDNA sequence to permit comparisons between human and mouse Tbx1. TBX1
      is a member of a phylogenetically conserved family of genes that share a common
      DNA-binding domain, the T-box. T-box genes are transcription factors involved in
      the regulation of developmental processes. There is 98% amino acid identity
      between human and mouse TBX1 proteins overall, and within the T-box domain, the
      proteins are identical except for two amino acids. Expression of human TBX1 in
      adult and fetal tissues, as determined by Northern blot analysis, is similar to
      that found in the mouse. Additionally, using 3 'RACE, we obtained a
      differentially spliced message in adult skeletal muscle. Mouse Tbx1 has been
      previously shown to be expressed during early embryogenesis in the pharyngeal
      arches, pouches, and otic vesicle. Later in development, expression is seen in
      the vertebral column and tooth bud. Thus, human TBX1 is a candidate for some of
      the features seen in the 22q11 deletion syndrome.

PMID- 9268630
TI  - Cloning, human chromosomal assignment, and adipose and hepatic expression of the
      CL-6/INSIG1 gene.
AB  - Rat CL-6 is the most highly insulin-induced gene in a liver cell line and is
      expressed in proliferating liver during regeneration and development. CL-6 is now
      denoted INSIG1 (insulin-induced gene 1). Human INSIG1 was isolated and found to
      be 80% identical to the rat gene within the translated region. It was located on
      human chromosome 7 within band q36. The human INSIG1 promoter conferred a high
      level of expression in both liver and fibroblast cell lines. INSIG1 expression
      was upregulated at the transcriptional level in rat regenerating liver and
      induced in a model of murine adipocyte differentiation, suggesting that INSIG1
      may play a role in growth and differentiation of tissues involved in metabolic
      control.

PMID- 9268631
TI  - Characterization of the C3 YAC contig from proximal mouse chromosome 17 and
      analysis of allelic expression of genes flanking the imprinted Igf2r gene.
AB  - The imprinted mouse insulin-like growth factor type 2 receptor (Igf2r) maps to
      the middle of a gene-rich region in band A2 of mouse chromosome 17. The t(Lub2)
      chromosome 17 variant contains a small deletion that removes at least seven genes
      including Igf2r. We have constructed a YAC contig spanning the entire t(Lub2)
      deletion and created a restriction map that covers 700 kb. The position,
      transcription orientation, and imprinted status of the genes immediately flanking
      Igf2r have been assessed. We show here that the Mas gene, which lies 65 kb
      upstream to Igf2r, contains a novel 5' exon and is not imprinted in adult
      tissues. We further show that the recently identified Lx1 gene lies immediately
      downstream and is also expressed from both parental alleles in adult tissues. The
      remaining genes in this region have previously been shown to be biallelically
      expressed.

PMID- 9268632
TI  - Structure and expression of the murine Sp100 nuclear dot gene.
AB  - The human SP100 gene encodes an autoantigen that colocalizes with two other
      proteins, PML and NDP52, in distinct nuclear domains, called "nuclear dots"
      (NDs). NDs do not overlap with other known subnuclear structures, and their
      function is still unknown. Patients suffering from the autoimmune disease primary
      biliary cirrhosis often produce antibodies against the SP100 protein. The present
      study describes the structure and expression of the murine Sp100 gene. In the
      species Mus caroli, Sp100 consists of 17 exons that are distributed over a range
      of 52 kb. The human and murine Sp100 promoters are very similar, and both harbor
      an interferon-stimulated response element. Like its human counterpart, the murine
      Sp100 gene is responsive to interferon treatment. The house mouse, Mus musculus,
      harbors the Sp100 gene and a second gene with homology to Sp100, the multicopy
      Sp100-rs gene. However, in contrast to the genuine mouse homolog, Sp100-rs shares
      only segmental homology with the human Sp100 gene. Replacement of the murine
      Sp100 gene by a defective copy is now feasible and should shed light on its
      function in an animal model.

PMID- 9268633
TI  - A method for genome comparisons and hybridization studies using known megabase
      scale DNA sequences as a reference.
AB  - We present a method for genome comparisons and high-resolution hybridization
      analyses using megabase stretches of known DNA sequences as a reference. The
      method employs two-dimensional gel electrophoresis, separating genomic segments
      cut with different restriction endonucleases in the first and second dimensions,
      to generate filters suitable for image analysis and repeated nucleic acid
      hybridizations. The corresponding two-dimensional pattern is computed from the
      reference nucleotide sequence and matched to the observed pattern, thereby
      identifying each fragment on the filter; at the same time the technique uncovers
      discrepancies from the reference sequence. This permits genome comparisons as
      well as automated identification and quantification of hybridization patterns
      with various probes. The technique is illustrated by an analysis of Saccharomyces
      cerevisiae chromosome IX.

PMID- 9268634
TI  - The human beta-defensin-1 and alpha-defensins are encoded by adjacent genes: two
      peptide families with differing disulfide topology share a common ancestry.
AB  - We cloned a novel human beta-defensin gene and determined its full-length cDNA
      sequence. The entire gene spanned more than 7 kb and included a large 6962-bp
      intron. The 362-bp cDNA encoded a prepropeptide that corresponded precisely to
      the recently identified human beta-defensin HBD-1, an antimicrobial peptide
      implicated in the resistance of epithelial surfaces to microbial colonization. By
      two-color fluorescence in situ hybridization on both metaphase chromosome and
      released chromatin fiber, HBD-1 gene (DEFB1 in HUGO/GDB nomenclature) mapped to
      chromosomal region 8p23.1-p23.2 in close proximity (within 100-150 kb) to the
      gene for the human neutrophil alpha-defensin HNP-1 (DEFA1). Thus, despite a
      complete lack of DNA sequence similarity and despite differences in their
      disulfide-pairing pattern, the alpha- and beta-families appear to have evolved
      from a common premammalian defensin gene.

PMID- 9268635
TI  - Cytoplasmic antiproteinase 2 (PI8) and bomapin (PI10) map to the serpin cluster
      at 18q21.3.
AB  - High-molecular-weight serine proteinase inhibitors (serpins) regulate a diverse
      set of intracellular and extracellular processes such as complement activation,
      fibrinolysis, coagulation, cellular differentiation, tumor suppression,
      apoptosis, and cell migration. The ov-serpins are a subset of the serpin
      superfamily and are characterized by their high degree of homology to chicken
      ovalbumin, the lack of N- and C-terminal extensions, the absence of a signal
      peptide, and a Ser rather than an Asn residue at the penultimate position.
      Recently, we mapped four members of the family [SCCA1, SCCA2, PAI2, and PI5
      (maspin)] to a 300-kb region within 18q21.3. Using a panel of 18q21.3 YAC clones,
      PCR, and DNA blotting, we mapped two additional ov-serpins, cytoplasmic
      antiproteinase 2 [CAP2 (PI8)] and bone marrow-associated serpin [bomapin (PI10)],
      to the same region. Three of the serpins, PI8, PI10, and PAI2 mapped to the same
      YACs, yA27D8 and yA24E4. We estimated that the size of the 18q21.3 serpin cluster
      spanned approximately 500 kb and contained at least six serpin genes. The order
      was cen-PI5, SCCA2, SCCA1, PAI2, PI10, PI8-tel. The clustering of serpins at
      18q21 provides new opportunities to study coordinate gene regulation and the
      evolution of gene families.

PMID- 9268636
TI  - Genomic structure of a novel LIM domain gene (ZNF185) in Xq28 and comparisons
      with the orthologous murine transcript.
AB  - Construction of a transcript map in the DXS52 region in Xq28 had previously led
      to the isolation of a cDNA with a LIM zinc finger domain in the carboxyl
      terminus. In parallel, the orthologous murine transcript was isolated from the
      syntenic region. The human and mouse cDNAs have been designated ZNF185 and
      Zfp185, respectively. By integrating the cDNA sequence with the cosmid-derived
      genomic sequence the exon-intron structure of the 3' end of the ZNF185 gene was
      resolved. Comparative sequence analyses of the human genomic sequence with the
      full-length murine cDNA facilitated prediction of the 5' end of the gene. The
      selective expression of three transcripts corresponding to the ZNF185 gene and a
      related gene was shown by Northern and Southern blots. In situ hybridizations
      revealed a nonubiquitous and stage-specific expression of Zfp185, especially in
      differentiating connective tissue. Since LIM proteins regulate cellular
      proliferation and/or differentiation by diverse mechanisms, and some have
      directly been associated with disease, conceivably ZNF185 may represent a
      candidate for a disease-causing gene linked to Xq28. Knowledge of the genomic
      structure will permit detailed mutation analyses.

PMID- 9268637
TI  - Repetin (Rptn), a new member of the "fused gene" subgroup within the S100 gene
      family encoding a murine epidermal differentiation protein.
AB  - We report the cloning and characterization of a murine epidermal differentiation
      gene, repetin (Rptn), exhibiting striking similarity to the genes of the
      intermediate filament-associated proteins profilaggrin and trichohyalin. The
      repetin gene consists of three exons and two introns. The first exon is short and
      untranslated. The deduced amino acid sequence distributed between exons II and
      III contains 1130 amino acids with a calculated molecular mass of 130 kDa and pI
      of 7.7. The amino terminus exhibits significant homology to the S100 proteins
      containing two calcium-binding motifs of the EF-hand type. The remainder coding
      sequence contains a central segment consisting of 49 tandem repeats of a 12-amino
      acid sequence rich in glutamines. By fluorescence in situ hybridization the
      repetin gene was localized to chromosome band 3 F1-2. Expression of repetin mRNA
      is detectable in the stratified internal epithelia of forestomach and tongue and
      to a lesser degree in normal skin epidermis, where it is restricted to the
      differentiated suprabasal cell layers. Based on its chromosomal localization, its
      genomic organization, and its stage-specific expression during late epidermal
      differentiation, as well as on the structural features of the encoded protein, we
      conclude that the repetin gene represents a novel member of the "fused gene"
      subgroup of the S100 gene family encoding multifunctional epidermal matrix
      proteins.

PMID- 9268638
TI  - A 2-Mb YAC contig and physical map covering the chromosome 8q12 breakpoint
      cluster region in pleomorphic adenomas of the salivary glands.
AB  - Pleomorphic adenomas are benign epithelial tumors originating from the major and
      minor salivary glands. Extensive cytogenetic studies have demonstrated that they
      frequently show chromosome abnormalities involving chromosome 8, with consistent
      breakpoints at 8q12. In previous studies, we have shown that these breakpoints
      are located in a 9-cM interval between MOS/D8S285 and D8S260. Here, we describe
      directional chromosome walking studies starting from D8S260 as well as D8S285.
      Using the CEPH and ICRF YAC libraries, these studies resulted in the construction
      of two nonoverlapping YAC contigs of about 2 and 5 Mb, respectively. Initial
      fluorescence in situ hybridization (FISH) analysis suggested that the majority of
      8q12 breakpoints clustered within the 2-Mb contig, which was mapped to the
      centromeric part of chromosome band 8q12. This contig has at least double
      coverage and consists of 34 overlapping YAC clones. The localization of the YACs
      was confirmed by FISH analysis. On the basis of mapping data of landmarks with an
      average spacing of 65 kb as well as restriction enzyme analysis, a long-range
      physical map was established for the chromosome region spanned by the 2-Mb
      contig. The relative positions of various known genes and expressed sequence tags
      within this contig were also determined. Subsequent FISH analyses of pleomorphic
      adenomas using YACs as well as cosmids revealed that all but two of the 8q12
      breakpoints in the primary tumors tested mapped within a 300-kb interval between
      the MOS proto-oncogene and STS EM156. The target gene affected by the chromosome
      aberrations mapping within this interval was recently shown to be the PLAG1 gene,
      which encodes a novel zinc finger protein.

PMID- 9268639
TI  - Genomic structure and chromosomal localization of human uroguanylin.
AB  - Uroguanylin, a member of the guanylin peptide family, is a novel peptide
      regulator in intestinal salt and water transport. We isolated the gene for
      uroguanylin from a human genomic library and determined its structure. This gene
      consists of three exons and two introns within an overall length of 2.5 kb. The
      5' flanking region has TATA and CAAT boxes. The gene also has multiple binding
      sites for promoter-specific transcription factor, activator protein-1, and
      activator protein-2, and a cAMP-regulated enhancer element. Fluorescence in situ
      hybridization showed the uroguanylin gene at human chromosome 1p33-p34. RNA blot
      analysis showed that human uroguanylin mRNA is expressed in the gastric fundus
      and pylorus as well as in the intestine.

PMID- 9268640
TI  - A 1-Mb physical map and PAC contig of the imprinted domain in 11p15.5 that
      contains TAPA1 and the BWSCR1/WT2 region.
AB  - We have constructed a 1-Mb contig in human chromosomal band 11p15.5, a region
      implicated in the etiology of several embryonal tumors, including Wilms tumor,
      and in Beckwith-Wiedemann syndrome. Cosmid, P1, PAC, and BAC clones were
      characterized by NotI/SalI digestion and hybridized to a variety of probes to
      generate a detailed physical map that extends from D11S517 to L23MRP. Included in
      the map are the CARS, NAP2, p57/KIP2, KVLQT1, ASCL2, TH, INS, IGF2, H19, and
      L23MRP genes as well as end probes isolated from PACs. The TAPA1 gene, whose
      protein product can transmit an antiproliferative signal, was also localized in
      the contig. However, Northern blot analysis demonstrated that its expression did
      not correlate with tumorigenicity in G401 Wilms tumor hybrids, suggesting that
      TAPA1 is not responsible for the tumor suppression associated with 11p15.5.
      Genomic clones were used as probes in FISH analysis to map the breakpoints from
      three Beckwith-Wiedemann syndrome patients and a rhabdoid tumor. Interestingly,
      each of the breakpoints disrupts the KVLQT1 gene, which is spread over a 400-kb
      region of the contig. Since 11p15.5 contains several genes with imprinted
      expression and one or more tumor suppressor genes, our contig and map provide a
      framework for characterizing this intriguing genetic environment.

PMID- 9268641
TI  - Identification and cloning of the human homolog (JAG1) of the rat Jagged1 gene
      from the Alagille syndrome critical region at 20p12.
AB  - Notch proteins are a family of closely related transmembrane receptors proven to
      be instrumental in cell fate decisions. Recently, Notch ligands Delta and Jagged
      have been identified in Drosophila and rat, respectively. We have isolated the
      human homolog of the rat Jagged1 gene, JAG1, from a CpG island in a YAC clone
      covering the Alagille syndrome critical region at chromosome 20p12 (tel-SNAP
      D20S186-cen). Alagille syndrome is an autosomal dominant disorder characterized
      by neonatal jaundice, paucity of intrahepatic bile ducts, and abnormalities of
      the heart, skeleton, and eyes. The human Jagged1 (JAG1), therefore, appears to be
      a strong candidate gene for this disease. Here we describe the identification,
      full-length cDNA cloning, expression patterns, and precise physical location of
      this gene within the Alagille syndrome critical region.

PMID- 9268642
TI  - High-resolution genetic map of the human glutamyl aminopeptidase gene (ENPEP).
AB  - The murine B-lymphocyte differentiation antigen BP-1/6C3 has been identified as
      glutamyl aminopeptidase (EAP), the gene symbol for which is ENPEP. Using genomic
      DNA encoding for human EAP as a probe, we identified the ENPEP gene location on
      human chromosome 4q25 by polymerase chain reaction analysis of a human/rodent
      somatic cell hybrid mapping panel and by fluorescence in situ hybridization.
      Using a radiation hybrid panel, the gene order around ENPEP was determined to be
      centromere-D4S1236-(570 kb)-ENPEP-(210 kb)-D4S262-(270 kb)-D4S953-(270 kb)-D4S474
      (570 kb)-IF. The linkage of ENPEP to complement factor I (IF) confirms the human
      chromosome band 4q25 localization predicted from the chromosomal location of
      murine ENPEP. Human ENPEP thus provides an additional marker for the long arm of
      chromosome 4 that should facilitate studies of this genomic region.

PMID- 9268643
TI  - Identification of a gene within the tandem array of red and green color pigment
      genes.
AB  - The tandem array of color pigment genes on chromosome Xq28 contains nested exons
      of a distinct gene. This gene (termed TEX28) is composed of five exons that span
      almost the entire distance between the protein-coding regions of the color
      pigment genes and a transketolase-related gene. Although most of the TEX28 gene
      is repeated within the color pigment gene array, the exclusion of exon 1 from the
      array is predicted to restrict transcription to a single copy of the gene. The
      TEX28 gene encodes a polypeptide of 410 amino acid residues. This polypeptide
      does not display significant homology with any known proteins in public
      databases. Transcripts of the gene (1.8 kb) were detected in testes, but not in
      any other tissue examined. Color vision disorders that result from the deletion
      of color pigment genes should be reappraised for associated phenotypes that may
      derive from disruption of the TEX28 gene.

PMID- 9268644
TI  - Closely spaced tandem arrangement of AQP2, AQP5, and AQP6 genes in a 27-kilobase
      segment at chromosome locus 12q13.
AB  - The aquaporins (AQPs) are a family of water-transporting proteins that facilitate
      osmotically driven water movement across cell plasma membranes. Among the seven
      human aquaporins cloned to date (AQPs 0-6), genes encoding the four most closely
      related aquaporins (AQP0, AQP2, AQP5, and AQP6) have been mapped to chromosome
      band 12q13, suggesting an aquaporin family gene cluster at this locus. To
      construct a physical map and identify novel aquaporin gene members on this
      cluster, a human CEPH B yeast artificial chromosome (YAC) library was screened by
      PCR using primers derived from exon 4 of AQP2 and AQP0 genes. A YAC clone with
      200 kb of human DNA was isolated and analyzed. Primary pulsed-field gel
      electrophoresis and Southern blot analysis indicated the presence of AQP2, AQP5,
      and AQP6 genes, but not AQP0. Restriction mapping and PCR analysis yielded a
      precise physical map in which the three aquaporin genes span only approximately
      27 kb in the order, transcriptional orientation, and spacer length 5'-AQP2-5 kb
      spacer-AQP5-7 kb spacer-AQP6-3'.

PMID- 9268645
TI  - Genomic organization of the faciogenital dysplasia (FGD1; Aarskog syndrome) gene.
AB  - Faciogenital dysplasia (FGDY; MIM 305400), or Aarskog syndrome, is an X-linked
      developmental disorder that adversely affects the formation of specific skeletal
      structures including elements of the face, the cervical vertebrae, and the distal
      extremities. FGD1, the gene responsible for faciogenital dysplasia, encodes a
      guanine nucleotide exchange factor that specifically activates Cdc42, a member of
      the Rho (Ras homology) family of p21 GTPases. By activating Cdc42, FGD1
      stimulates fibroblasts to form filopodia, cytoskeletal elements involved in
      cellular signaling and migration, and through Cdc42, FGD1 also activates the
      stress-activated protein kinase/c-Jun N-terminal kinase signaling cascade, a
      pathway that regulates cell growth and differentiation. Here, we report a
      detailed characterization of the genomic organization of the FGD1 gene. The FGD1
      gene is composed of 18 exons that range in size from 31 to 1240 bp. These exons
      span over 51 kb of genomic DNA within region Xp11.21. Flanking intronic sequences
      and the sequence of the 5' and 3' untranslated regions were determined to
      facilitate the detection of FGDY patient mutations. Analyses show that FGD1
      transcripts are differentially spliced; in brain and placenta an alternatively
      spliced form of the FGD1 transcript removes part of the Cdc42GEF domain to encode
      a null Cdc42 activator.

PMID- 9268646
TI  - Assignment of the human B-cell-derived (BCD1) proto-oncogene to 10p14-p15.

PMID- 9268647
TI  - Zfy2/1 fusion gene fails to replicate Zfy1 expression pattern in fetal gonads.

PMID- 9268648
TI  - Mapping of the human DNA primase 1 (PRIM1) to chromosome 12q13.

PMID- 9268649
TI  - Tension in haemoglobin revealed by Fe-His(F8) bond rupture in the fully liganded
      T-state.
AB  - In 1972, Perutz proposed that the low affinity of T-state haemoglobin is caused
      by tension in the bond between the iron and the proximal histidine, restraining
      the Fe from moving into the porphyrin plane on binding oxygen. This proposal has
      often been disputed. If such tension does exist, it will be manifest in the
      liganded T-state. Here we describe the structure of the fully liganded T-state
      cyanide complex of haemoglobin, in which the Fe-proximal histidine bond in the
      alpha-subunits, but not in the beta-subunits, is ruptured. This rupture uncouples
      the structural changes at the alpha-haem from those in the globin and the beta
      haem, and demonstrates unequivocally the existence of tension and its
      transmission through this bond.

PMID- 9268650
TI  - RecA protein assisted selection reveals a low fidelity of recognition of homology
      in a duplex DNA by an oligonucleotide.
AB  - We have developed an in vitro selection procedure to elucidate the specificity of
      RecA assisted oligonucleotide recognition of double stranded DNA. The procedure
      was based on formation of a synaptic complex between an oligonucleotide-RecA
      filament and a supercoiled plasmid bearing a homologous partially degenerate
      region. The specificity of the selection depended on the reaction conditions:
      starting with a population that had, on average, 2.8 randomly distributed
      mismatches out of 27 bp, a population selected in the presence of 100 mM KCl had
      on average 1.0 mismatches, while a population selected at low ionic strength was
      less specific and had, on average, 2.0 mismatches. From the distributions of
      mismatches observed we calculated that the average destabilization free energy
      for one mismatch is 1.7(+/-0.5) kcal/mol. This is substantially less than the
      free energy for the incorporation of one mismatch in naked DNA duplex or a Py-Pu
      Py triplex. Thus, RecA has an ability to decrease the fidelity of the homologous
      pairing reaction and minimize the cost of pairing between similar but not
      identical sequences. This "antiproofreading" activity of RecA protein does not
      require ATP hydrolysis.

PMID- 9268651
TI  - Quantitative specificity of the Mnt repressor.
AB  - The Mnt protein of Salmonella phage P22 binds site-specifically to its operator.
      To better understand this binding we used dideoxy DNA sequencing in a
      quantitative manner to determine the relative binding constants, and hence the
      relative free energies, of wild-type Mnt protein to a substantial number of
      variants of its operator. These measurements were supported by experiments which
      used the SELEX procedure to generate a set of operators from an initially
      randomized population. In the Discussion we show that the present model of Mnt
      protein/operator binding, due to Sauer and co-workers, along with the assumption
      of an independent contribution of each position in the operator to the total
      binding, provides a reasonably accurate description of the system. We also
      discuss the use of information content as a measure of DNA-protein binding
      specificity with the Mnt protein/operator system serving as an example and show
      again that the assumption of independence supports the current view of this case
      of site-specific binding.

PMID- 9268652
TI  - A Xenopus zinc finger protein that specifically binds dsRNA and RNA-DNA hybrids.
AB  - Proteins containing C2H2 type zinc finger motifs represent one of the largest
      classes of nucleic acid-binding proteins found in nature. We describe a novel
      zinc finger protein, dsRBP-ZFa, isolated by screening an expression library with
      dsRNA. The dsRBP-ZFa cDNA encodes a protein containing seven zinc finger motifs
      and an acidic C-terminal domain. Mobility shift experiments demonstrate that
      dsRBP-ZFa binds dsRNA and RNA-DNA hybrids with nanomolar dissociation constants
      and in a sequence independent manner. We also show that DNA and single stranded
      RNA fail to compete with dsRNA for binding suggesting dsRBP-ZFa prefers to bind
      an A-form helix. Using western analyses we have localized dsRBP-ZFa primarily to
      the nucleus of Xenopus laevis oocytes. The identification of dsRBP-ZFa provides
      the first example of a zinc finger protein that is specific for dsRNA. In
      addition, dsRBP-ZFa does not contain the previously described dsRNA binding
      motif, suggesting certain zinc fingers may provide an alternative way to
      recognize the A-form helix.

PMID- 9268653
TI  - Three modified nucleosides present in the anticodon stem and loop influence the
      in vivo aa-tRNA selection in a tRNA-dependent manner.
AB  - In Salmonella typhimurium seven tRNA species specific for leucine, proline and
      arginine have 1-methylguanosine (m1G) next to and 3' of the anticodon (position
      37 of tRNA), five tRNA species specific for phenylalanine, serine, tyrosine,
      cysteine and tryptophan have 2-methylthio-N-6-(cis-hydroxy)isopentenyladenosine
      (ms2io6A) in the same position of the tRNA, and four tRNA species, specific for
      leucine and proline, have pseudouridine (Psi) as the last 3' nucleotide in the
      anticodon loop (position 38) or in the anticodon stem (positions 39 and 40).
      Mutants deficient in the synthesis of these modified nucleosides have been used
      to study their role in the first step of translation elongation, i.e. the aa-tRNA
      selection step in which the ternary complex (EF-Tu-GTP-aa-tRNA) binds at the
      cognate codon in the A-site on the mRNA programmed ribosome. We have found that
      the Psi present in the anticodon loop (position 38) stimulates the selection of
      tRNA specific for leucine whereas Psi in the anticodon stem did not affect the
      selection of tRNA specific for proline. The m1G37 strongly stimulates the rate of
      selection of the three tRNA species specific for proline and one tRNA species
      specific for arginine but has only minor or no effect on the selection of the
      three tRNA species specific for leucine. Likewise, the ms2io6A, present in the
      same position as m1G37 but in another subset of tRNA species, stimulates the
      selection of tRNA specific for tyrosine, stimulates to some extent also tRNA
      species specific for cysteine and tryptophan, but has no influence on the rate of
      selection of tRNA specific for phenylalanine. We conclude that function of m1G
      and ms2io6A present next to and 3' of the anticodon influences the in vivo aa
      tRNA selection in a tRNA-dependent manner.

PMID- 9268654
TI  - cDNAs derived from primary and small cytoplasmic Alu (scAlu) transcripts.
AB  - We have isolated and sequenced twenty-six cDNAs derived from primary Alu
      transcripts. Most cDNAs (22/26) sequenced end in multiple T residues, known to be
      at the termination for RNA polymerase III-directed transcripts. We conclude that
      these cDNAs were derived from authentic, RNA polymerase III-directed primary Alu
      transcripts. Sequence alignment of the cDNAs with Alu consensus sequences show
      that the cDNAs belong to different, previously described Alu subfamilies. The
      sequence variation observed in the 3' non-Alu regions of each of the cDNAs led us
      to conclude that they were derived from different genomic loci, thus
      demonstrating that multiple Alu loci are transcriptionally active. The subfamily
      distribution of the cDNAs suggests that transcriptional activity is biased
      towards evolutionarily younger Alu subfamilies, with a strong selection for the
      consensus sequence in the first 42 bases and the promoter B box. Sequence data
      from seven cDNAs derived from small cytoplasmic Alu (scAlu) transcripts, a
      processed form of Alu transcripts, also have a similar bias towards younger Alu
      subfamilies. About half of these cDNAs are due to processing or degradation, but
      the other half appear to be due to the formation of a cryptic RNA polymerase III
      termination signal in multiple loci. Using our sequence data, we have isolated a
      transcriptionally active genomic Alu element belonging to the Ya5 subfamily. In
      vitro transcription studies of this element suggest that its flanking sequences
      contribute to its transcriptional activity. The role of flanking sequences and
      other factors involved in transcriptional activity of Alu elements are discussed.

PMID- 9268655
TI  - Modulation of yeast F-actin structure by a mutation in the nucleotide-binding
      cleft.
AB  - Although the actin sequence is very highly conserved across evolution, tissue
      specific expression of different isoforms in high eukaryotes suggests that
      different isoforms carry out different functions. However, little information
      exists about either the differences in filaments made from different actins or
      the effects on filament structure caused by the various mutations in actin that
      have been introduced to gain insight into actin function. Using electron
      microscopy and three-dimensional reconstruction, we have studied the differences
      in the filaments made by yeast and rabbit skeletal muscle actin, two proteins
      with 88% homologous sequences, and we have assessed the changes in filament
      structure caused by the introduction of the S14A mutation into yeast actin.
      Elimination of the S14 hydroxyl group, assumed to bind to the gamma-phosphate of
      actin-bound ATP, results in a 40 to 60-fold decrease in actin's affinity for ATP.
      We show that yeast actin displays less extensive contacts between the two long
      pitch helical strands than does muscle actin, and displays the large
      cooperativity within filaments previously observed for muscle actin. Finally, we
      demonstrate that the S14A mutation narrows the cleft between the two lobes of the
      actin subunit and strengthens the inter-strand connections in F-actin.

PMID- 9268656
TI  - Specific binding of hoechst 33258 to the d(CGCAAATTTGCG)2 duplex: calorimetric
      and spectroscopic studies.
AB  - Fluorescence spectroscopy and high-sensitivity isothermal titration calorimetry
      (ITC) techniques have been used to examine the binding characteristics of Hoechst
      33258 with the extended AT-tract DNA duplex d(CGCAAATTTGCG)2 in aqueous solution.
      The method of continuous variation reveals a 1:1 binding stoichiometry.
      Fluorescence equilibrium studies carried out at three different, but fixed,
      ligand concentrations show that the binding isotherm shifts towards higher [DNA]
      as the concentration of ligand is increased. The data show tight binding with
      Kb=3.2(+/-0.6)x10(8) M(duplex)-1 at 25 degrees C in solutions containing 200 mM
      Na+. Based on UV studies of duplex melting, which show that strand separation
      starts at approximately 35 degrees C and has a Tm at 54 degrees C in 300 mM NaCl,
      binding enthalpies were determined by ITC in the 10 to 30 degrees C range.
      Binding is endothermic at all temperatures examined, with DeltaH values ranging
      from +10.24(+/-0.18) to +4.2(+/-0.10) kcal mol(duplex)-1 at 9.4 degrees C and
      30.1 degrees C, indicating that the interaction is entropically driven. The
      temperature dependence of DeltaH shows a binding-induced change in heat capacity
      (DeltaCp) of -330(+/-50) cal mol-1 K-1. This value is similar to that predicted
      from a consideration of the effects of hydrophobic and hydrophilic solvent
      accessible surface burial on complexation. This result, almost entirely dictated
      by a removal from exposure of the non-polar reactant surfaces, represents the
      first demonstration of such behavior in a DNA-drug system. The salt dependence of
      the binding constant was examined using reverse-salt fluorescence titrations,
      with a value of 0.99 determined for the deltalnK/deltaln[Na+] parameter. These
      data provide a detailed thermodynamic profile for the interaction that enables a
      dissection of DeltaGobs into the component free energy terms. Analysis of data
      obtained at 25 degrees C reveals that DeltaGobs is dominated by the free energy
      for hydrophobic transfer of ligand from solution to the DNA binding site.
      Molecular interactions, including H-bonding and van der Waals contacts, are found
      to play only a minor role in stabilizing the resulting complex, a somewhat
      surprising finding given the emphasis placed on such interactions from structural
      studies.

PMID- 9268657
TI  - Crystal structure of cytoplasmic Escherichia coli peptidyl-prolyl isomerase:
      evidence for decreased mobility of loops upon complexation.
AB  - The structure of the unliganded form of the Escherichia coli cytoplasmic peptidyl
      prolyl isomerase (ppiB gene product) in a new crystal form was determined by the
      molecular replacement method and refined to an R-factor of 16.1% at 2.1 A
      resolution. The enzyme crystallized in the orthorhombic C2221 space group with
      unit cell dimensions of a=44.7 A, b=68.2 A and c=102.0 A. Comparison with the
      reported structure of the enzyme complexed with the tripeptide substrate succinyl
      Ala-Pro-Ala-p-nitroanilide revealed subtle changes that occur upon complex
      formation. There is evidence to suggest that two surface loops have significantly
      reduced mobility in the complexed structure.

PMID- 9268658
TI  - NMR structural studies of human cystatin C dimers and monomers.
AB  - Human cystatin C undergoes dimerization before unfolding. Dimerization leads to a
      complete loss of its activity as a cysteine proteinase inhibitor. A similar
      process of dimerization has been observed in cells, and may be related to the
      amyloid formation seen for the L68Q variant of the protein. Dimerization is
      barrier controlled, and no dimer/monomer interconversion can be observed at
      physiological conditions. As a consequence, very stable, "trapped" dimers can be
      easily separated from monomers. A study of the structural aspects of cystatin C
      dimer formation was undertaken using NMR spectroscopy. The monomer/dimer model
      was verified by (pulse field gradient NMR) self-diffusion molecular mass
      measurements. Complete backbone resonance assignments and secondary structure
      determination were obtained for the monomer using data from triple resonance
      experiments performed on 13C/15N doubly labeled protein. A marked similarity of
      the cystatin C secondary structure to that of chicken cystatin was observed.
      Using uniformly and amino-acid-specific 15N-enriched protein, backbone NH signals
      were assigned for cystatin C in its dimeric state. Comparison of 1H -15N
      correlation NMR spectra of the monomer and dimer shows that the three-dimensional
      structure remains unchanged in the dimer and that only local perturbations occur.
      These are localized to the amino acid residues comprising the cysteine proteinase
      binding site. Such a mode of dimerization readily explains the complete loss of
      the inhibitory activity in the dimer. The NMR results also demonstrate that the
      dimer is symmetric.

PMID- 9268659
TI  - Topology of T cell receptor-peptide/class I MHC interaction defined by charge
      reversal complementation and functional analysis.
AB  - The molecular interactions between the CD8 co-receptor dependent N15 and N26 T
      cell receptors (TCRs) and their common ligand, the vesicular stomatitis virus
      octapeptide (VSV8) bound to H-2Kb, were studied to define the docking
      orientation(s) of MHC class I restricted TCRs during immune recognition. Guided
      by the molecular surfaces of the crystallographically defined peptide/MHC and
      modeled TCRs, a series of mutations in exposed residues likely contacting the TCR
      ligand were analyzed for their ability to alter peptide-triggered IL-2 production
      in T cell transfectants. Critical residues which diminished antigen recognition
      by 1000 to 10,000-fold in molar terms were identified in both N15 Valpha
      (alphaE94A or alphaE94R, Y98A and K99) and Vbeta (betaR96A, betaW97A and
      betaD99A) CDR3 loops. Mutational analysis indicated that the Rp1 residue of VSV8
      is critical for antigen recognition of N15 TCR, but R62 of H-2Kb is less
      critical. More importantly, the alphaE94R mutant could be fully complemented by a
      reciprocal charge reversal at Kb R62 (R62E). This result suggests a direct
      interaction between N15 TCR Valpha E94R and Kb R62E residues. As Rp1 of VSV8 is
      adjacent to R62 in the VSV8/Kb complex and essential for T cell activation, this
      orientation implies that the N15 Valpha CDR3 loop interacts with the N-terminal
      residues of VSV8 with the Valpha domain docking to the Kb alpha2 helix while the
      N15 Vbeta CDR3 loop interacts with the more C-terminal peptide residues and the
      Vbeta domain overlies the Kb alpha1 helix. An equivalent orientation is suggested
      for N26, a second VSV8/Kb specific TCR. Given that genetic analysis of two
      different class II MHC-restricted TCRs and two crystallographic studies of class
      I restricted TCRs offers a similar overall orientation of V domains relative to
      alpha-helices, these data raise the possibility of a common docking mode between
      TCRs and their ligands regardless of MHC restriction.

PMID- 9268660
TI  - Translational activation in coliphage Qbeta: on a polycistronic messenger RNA,
      repression of one gene can activate translation of another.
AB  - We present evidence for translational activation of the Qbeta coliphage
      maturation cistron, mediated by the presence of Qbeta replicase. This activation
      does not require RNA replication, translation of a second gene, or any direct
      protein-RNA binding at the maturation gene initiation site. Our data support a
      model in which the Qbeta maturation gene remains translationally "off" by two
      means: (1) the thermodynamic stability of an RNA structure that greatly
      discourages, but does not eliminate, ribosome access at the maturation start
      site; and (2) the presence of the stronger, proximal coat gene ribosome binding
      site. Moreover, maturation gene expression is switched "on" when ribosome entry
      at the coat initiation site, present on the same polycistronic RNA molecule, is
      repressed by Qbeta replicase, thereby allowing ribosomes to compete for the
      weaker, upstream maturation start site.

PMID- 9268661
TI  - De novo and DNA primer-mediated initiation of cDNA synthesis by the mauriceville
      retroplasmid reverse transcriptase involve recognition of a 3' CCA sequence.
AB  - The Mauriceville mitochondrial retroplasmid of Neurospora encodes a novel reverse
      transcriptase that initiates cDNA synthesis at a 3' tRNA-like structure of the
      plasmid transcript, either de novo (i.e. without a primer) or by using the 3' OH
      group of a DNA primer. Both the de novo and primer-mediated initiations involve
      recognition of structural features at the 3' end of the retroplasmid transcript,
      which ends with a 3' CCACCA. Here, detailed biochemical characterization of the
      retroplasmid reverse transcriptase shows that the 3' CCA of the plasmid
      transcript is the major structural feature recognized by the reverse
      transcriptase for both the de novo and primer-mediated initiations.
      Complementarity between the DNA primer and RNA template is not required for the
      primer-mediated initiation, although short (1 to 3 nt) base-pairing interactions
      can influence both the efficiency and site of initiation near the 3' end of the
      transcript. Single nucleotide changes in the 3' CCA lead to less efficient
      initiation in the upstream CCA with an increased propensity to add extra "non
      coded" nucleotides to the 5' end of the cDNA during de novo initiation or to the
      3' end of the primer during primer-mediated initiation. Secondary structure
      features upstream of the 3' CCA also influence the efficiency of initiation, but
      are not stringently required in vitro. Finally, we find that the retroplasmid
      reverse transcriptase does not efficiently use DNA primers that are base-paired
      to internal positions in the RNA template, nor does it use analogs of natural
      substrates used by non-long terminal repeat retrotransposon or retroviral reverse
      transcriptases. Our results indicate that the retroplasmid reverse transcriptase
      is uniquely adapted to initiate cDNA synthesis by recognizing a 3' CCA sequence.
      The ability to recognize a specific template sequence is common for RNA
      polymerases, but unprecedented for a reverse transcriptase.

PMID- 9268663
TI  - KpnAI, a new type I restriction-modification system in Klebsiella pneumoniae.
AB  - The KpnAI restriction-modification (R-M) system has been identified in Klebsiella
      pneumoniae strain M5a1. The restriction gene of KpnAI was first cloned into
      pBR322 using an r-m+ M5a1 derivative and phage SBS for screening. Subsequently,
      an adjacent DNA fragment showing modification activity was cloned into pUC19. A
      total of 7.2 kb DNA sequencing data revealed three open reading frames,
      corresponding to hsdR, hsdM and hsdS genes of type I R-M systems. The predicted
      hsdR, hsdM and hsdS-coded peptides shared 95%, 98% and 44% identity,
      respectively, with the corresponding peptides of the recently identified StySBLI
      system, a prototype of the type ID family. This high homology suggests that KpnAI
      is also a member of the type ID family. The KpnAI system seems to be the first
      type I system identified in Klebsiella species.

PMID- 9268662
TI  - Sequences of antigenic epitopes of streptokinase identified via random peptide
      libraries displayed on phage.
AB  - Though streptokinase (SK) is widely used to treat humans with thrombotic disease,
      it is antigenic and anti-SK antibody causes allergic reactions and neutralizes
      SK's therapeutic effects. To pinpoint the fine structure of two immunodominant,
      continuous epitopes in SK, we used unconstrained 15 and 6-mer random peptide
      libraries displayed on phage (theoretical complexity of 3.2 x 10(19) and 0.64 x
      10(8) unique sequences). The first epitope, recognized by both human Ab and
      murine monoclonal (m)Abs, was previously localized to the amino terminus of SK.
      Repeated panning and selection experiments against a 15-mer peptide phage
      library, using a representative mAb (A2.5) to this epitope, identified a dominant
      structural motif (GP[R/L]WL) corresponding to amino acids 3 to 7 of native SK,
      which was consistent with previous epitope mapping. These findings were further
      confirmed by: (1) the fact that a synthetic peptide spanning the epitope of A2.5
      (AGPEWLL) specifically inhibited the binding of A2.5 to SK and (2) the finding
      that mAb 9D10, which competes with mAb A2.5 for binding to SK, independently
      selected, from a different random hexamer library, an epitope sequence spanning
      residues 4 to 9 that overlaps the A2.5 epitope. Similar studies of the second
      epitope in SK, which is immunodominant for murine but not human antibodies,
      identified a consensus sequence KS(K/L)P(F/Y) corresponding to amino acids 59 to
      63 of SK; this was confirmed by epitope peptide binding experiments. This epitope
      is cleaved and destroyed when SK reacts with human but not murine plasminogen.
      Thus, pinpointing the sequences of antigenic epitopes of SK: (1) provides a
      potential explanation for species differences in SK's antigenicity, (2)
      demonstrates the overlapping fine structure of epitopes recognized by competitive
      mAbs, (3) confirms previous epitope mapping studies and (4) has the potential to
      identify antigenic sequences that lead to allergic reactions in patients treated
      with SK.

PMID- 9268664
TI  - Triple-helical DNA as a reversible block of the branch point in a partially
      symmetrical DNA four-arm junction.
AB  - DNA branch migration is a fundamental process in genetic recombination. A new
      model system has been developed for studying branch migration in a small
      synthetic four-arm junction. A mathematical method for describing branch-point
      movement by discrete steps in such junctions is also presented. The key to our
      experimental system is the ability to fix the location of the branch point during
      the assembly of the junction with a reversible block. The block is provided by a
      short oligonucleotide that forms triplex DNA adjacent to the initial location
      branch point at low pH. Raising the pH causes the triplex strand to dissociate,
      making the branch point free to migrate. Once mobile, the branch point can run
      off the end of the junction. The time-course for this runoff is consistent with a
      random walk of the branch point. If it is assumed that one migration step moves
      the branch point one base-pair, the time-course gives a rate constant for one
      step of 1.4 second-1 at 37 degrees C in 10 mM MgCl2, 50 mM NaCl. These values are
      consistent with other measurements of non-enzymatic branch migration. We have
      also monitored the spread of the branch points directly with T4 endonuclease VII.
      Using EcoRI restriction endonuclease, we have shown that the binding of this
      protein to the arms of the junction essentially blocks branch migration through
      the binding site. In these experiments Ca2+ replaces Mg2+, and the enzyme does
      not cleave the DNA. In vivo there must be a special process to get branch points
      to migrate past bound proteins.

PMID- 9268665
TI  - Tn5 transposase mutants that alter DNA binding specificity.
AB  - Tn5 transposase (Tnp) binds to Tn5 and IS50 end inverted repeats, the outside end
      (OE) and the inside end (IE), to initiate transposition. We report the isolation
      of four Tnp mutants (YH41, TP47, EK54 and EV54) that increase the OE-mediated
      transposition frequency and enhance the binding affinity of Tnp for OE DNA. In
      addition, two of the Tnp mutants (TP47 and EK54) appear to be change-of
      specificity mutants, since they alter the recognition of OE versus IE relative to
      the wild-type Tnp. EK54 enhances OE recognition but decreases IE recognition.
      TP47 enhances both OE and IE recognition but with a much greater enhancement for
      IE than for OE. This change-of-specificity effect of TP47 is observed only when
      TP47 Tnp is synthesized in cis to the DNA that contains the ends. We propose that
      Lys54 makes a favorable interaction with an OE-specific nucleotide pair(s), while
      Pro47 may cause a more favorable interaction with an IE-specific nucleotide
      pair(s) than it does with the corresponding OE-specific nucleotide pair(s). A
      model to explain the preference of TP47 Tnp for the IE in cis but not in trans is
      proposed.

PMID- 9268666
TI  - Cleavage specificity of a proteolytic antibody light chain and effects of the
      heavy chain variable domain.
AB  - The recombinant light chain (L chain) of an antibody raised by immunization with
      vasoactive intestinal polypeptide (VIP) cleaved this peptide on the C-terminal
      side of basic residues. The major sites of cleavage in VIP were two adjacent
      peptide bonds, Lys20-Lys21 and Lys21-Tyr22. Lower levels of cleavage were evident
      at Arg14-Lys15 and Lys15-Gln16. Hydrolysis of radiolabeled VIP by the L chain was
      inhibited by two serine protease inhibitors, diisopropylfluorophosphate and
      aprotinin, but not by soybean or lima bean trypsin inhibitors or inhibitors of
      other classes of proteases. To probe the role of the VH domain, single chain Fv
      constructs composed of the VL domain of the anti-VIP L chain linked via a 14
      residue peptide to its natural VH domain partner or an irrelevant anti-lysozyme
      VH domain (hybrid Fv) were prepared. The anti-VIP Fv hydrolyzed VIP with Ks 21.4
      fold lower than the L chain and 250-fold lower than the hybrid Fv, suggesting
      increased affinity for the substrate ground state due to the anti-VIP VH domain.
      The kinetic efficiency (kcat/Ks) of the anti-VIP Fv was 6.6-fold greater compared
      to the L chain and 29.4-fold greater compared to the hybrid Fv. Peptide-MCA
      substrates unrelated in sequence to VIP were hydrolyzed by the anti-VIP Fv and L
      chain at equivalent rates. These observations lead to a model of catalysis by the
      anti-VIP Fv in which the essential catalytic residues are located in the VL
      domain and additional residues from the VH domain are involved in high affinity
      binding of the substrate.

PMID- 9268667
TI  - Large genome rearrangements discovered by the detailed analysis of 21 Pseudomonas
      aeruginosa clone C isolates found in environment and disease habitats.
AB  - In order to determine primary genetic events which occur during the
      diversification of a Pseudomonas aeruginosa clone in natural habitats,
      comparative genome analysis of 21 isolates of a predominant clone, called clone
      C, derived mainly from patients with cystic fibrosis (CF) and the aquatic
      environment, was carried out. Physical chromosome maps were constructed for the
      restriction enzymes SpeI, PacI, SwaI and I-CeuI by one and two-dimensional pulsed
      field gel electrophoresis and by comparison with the existing strain C map. The
      positioning of 26 genes generated the genetic maps. Chromosome size varied
      between 6345 and 6606 kilobase-pairs (kb). A plasmid of 95 kb was detected in the
      strains of non-CF origin and, in addition, was found to be integrated into the
      chromosome of all strains but one CF isolate. Four subgroups of clone C strains
      were discriminated by the acquisition and loss of large blocks of DNA that could
      cover more than 10% of the chromosome size. The exchange of DNA blocks which
      ranged in size from 1 kb to 214 kb occurred preferentially around the terminus of
      replication region which is poor in biosynthetic genes. Genetic material which
      was additionally introduced into strain C in comparison with strain PAO seems to
      be a target of mutational processes in clone C strains. Within and among
      subgroups CF isolates frequently exhibited large inversions affecting the whole
      chromosomal structure. We concluded that the exchange of DNA blocks by mechanisms
      of horizontal transfer and large chromosomal inversions are major factors leading
      to the divergence of a clone in the species P. aeruginosa.

PMID- 9268668
TI  - Chloride and proton transport in bacteriorhodopsin mutant D85T: different modes
      of ion translocation in a retinal protein.
AB  - Replacement of aspartate 85 (D85) in bacteriorhodopsin (BR) by threonine but not
      be asparagine creates at pH<7 an anion-binding site in the molecular similar to
      that in chloride pump halorhodopsin. Binding of various anions to BR-D85T causes
      a blue shift of the absorption maximum by maximally 57 nm. Connected to this
      color change is a change in the absorption difference spectrum of the initial
      state and the longest living photo intermediate from a positive difference
      maximum at 460 nm in the absence of transported anions to one at 630 nm in their
      presence. Increasing anion concentration cause decreasing decay times of this
      intermediate. At physiological pH, BR-D85T but not BR-D85N transports chloride
      ions inward in green light, protons outward in blue or green light and protons
      inward in white light (directions refer to the intact cell). The proton movements
      are observable also in BR-D85N. Thus, creation of an anion-binding site in BR is
      responsible for chloride transport and introduction of anion-dependent
      spectroscopic properties at physiological pH. The different transport modes are
      explained with the help of the recently proposed IST model, which states that
      after light-induced isomerization of the retinal an ion transfer step and an
      accessibility change of the active site follow. The latter two steps occur
      independently. In order to complete the cyclic event, the accessibility change,
      ion transfer and isomerization state have to be reversed. The relative rates of
      accessibility changes and ion transfer steps define ultimately the vectoriality
      of ion transfers. All transport modes described here for the same molecule can
      satisfactorily be described in the framework of this general concept.

PMID- 9268669
TI  - Structure of keyhole limpet hemocyanin type 1 (KLH1) at 15 A resolution by
      electron cryomicroscopy and angular reconstitution.
AB  - A three-dimensional reconstruction of keyhole limpet hemocyanin type 1 (KLH1) has
      been obtained using electron cryomicroscopy at liquid helium temperatures and
      single particle image processing. The use of a high-contrast embedding medium, 1%
      (w/v) glucose and 2% (w/v) ammonium molybdate (pH 7.0), enables high-resolution
      electron micrographs to be recorded close to focus, i.e. with excellent transfer
      of high-resolution information, while maintaining enough image contrast to
      localise the individual macromolecules in the images. When low-pass filtered to
      approximately 45 A resolution, the new 15 A resolution reconstruction is very
      similar to the earlier reconstructions of gastropodan hemocyanins of specimens
      embedded in vitreous ice. The map shows much detail and reveals many new symmetry
      elements in this very large cylindrical molluscan hemocyanin. The full KLH1
      didecamer has D5 pointgroup symmetry, yet within the KLH1 decameric half
      molecules local 2-fold axes have emerged that make the wall of the KLH1 decamer,
      in spite of its having an exact C5 symmetry only, resemble the D5-symmetric wall
      of the decameric cephalopod hemocyanins. In fact, the outside of each tier of
      this six-tiered gastropodan hemocyanin was found to have an approximate D5
      symmetry. Local 2-fold axes also relate the "functional units" within the dimeric
      "morphological units" of the wall and the collar areas of the 8 MDa KLH1
      molecule. Certain local-symmetry-related surface motifs may be present up to 60
      times on the outside wall of this highly symmetric cylindrical hemocyanin.
      Keyhole limpet hemocyanin is used clinically as an immunostimulant. The very
      strong immune reaction elicited by this hemocyanin may be associated with its
      intricate hierarchy of local-symmetry components.

PMID- 9268670
TI  - Unique base-pair breathing dynamics in PNA-DNA hybrids.
AB  - Kinetic and thermodynamic parameters, derived from 1H-NMR measurements of the
      imino proton exchange rates upon titration with the exchange catalyst ammonia,
      are reported for two mixed-sequence peptide nucleic acid (PNA)-DNA hybrids and
      their counterpart DNA duplex. The exchange times of the imino protons in the PNA
      strands extrapolate to very short base-pair lifetimes in the limit of infinite
      exchange catalyst concentration. This is not due to generally less stable base
      pairs in PNA-DNA hybrids, since the lifetimes, apparent dissociation constants
      and thermodynamic stability (DeltaG degrees ) of the innermost DNA guanine imino
      protons are similar in the hybrid duplexes and in the DNA duplex. In addition,
      the apparent dissociation constants determined for PNA bases of the hybrids are
      of the same order as those of the corresponding bases in the DNA duplex. An
      exchange process from the closed state was found to be inconsistent with the
      experimental data. From these results, we conclude that opening and closing rates
      of the PNA guanine and thymine bases are at least two orders of magnitude higher
      than those of the corresponding bases in the DNA duplex. Unusual kinetics in the
      hybrids is also evident from the destabilization of the complementary DNA strand
      thymine bases, which exhibit base-pair dissociation constants increased by
      approximately two orders of magnitude compared to what is observed in the DNA
      duplex, while the DNA strand guanine bases are largely unaffected. The general
      pattern of the base-pair dynamics in the hybrids obtained when using
      trimethylamine as an exchange catalyst is the same as when using ammonia.
      However, the long base-pair lifetimes i. e. those of the DNA duplex and the
      guanine bases of the DNA strands in the hybrids, are approximately three to five
      times longer than when using ammonia. Thus, all opening events sensed by ammonia
      are not accessible to trimethylamine. These observations are discussed in regard
      to the mechanism of base-pair opening and the nature of the open state.

PMID- 9268671
TI  - Crystal structure of the bacteriochlorophyll a protein from Chlorobium tepidum.
AB  - The bacteriochlorophyll (BChl) a protein from Chlorobium tepidum, which
      participates in energy transfer in green photosynthetic bacteria, has been
      crystallized using the sitting drop method of vapor diffusion. X-ray diffraction
      data collected from these crystals indicate that the crystals belong to the cubic
      space group P4132 with cell dimensions of a=b=c=169.5 A. A native X-ray
      diffraction data set has been collected to a resolution of 2.2 A. The initial
      solution was determined by using the molecular replacement method using the
      structure of the previously solved BChl a protein from Prosthecochloris
      aestuarii. A unique rotation and translation solution was obtained for two
      monomers in the asymmetric unit giving a pseudo-body centered packing. After
      rebuilding and refinement the model yields an R factor of 19.0%, a free R-factor
      of 28.3%, and good geometry with root-mean-square deviations of 0.013 A and 2.1
      degrees for the bond lengths and angles, respectively. The structure of the BChl
      a protein from C. tepidum consists of three identical subunits related by a 3
      fold axis of crystallographic symmetry. In each subunit the polypeptide backbone
      forms large beta-sheets and encloses a central core of seven BChl a molecules.
      The distances between neighboring bacteriochlorin systems within a subunit range
      between 4 A to 11 A and that between two bacteriochlorins from different subunits
      is more than 20 A. The overall structure is comparable with that of P. aestuarii
      but significant differences are observed for the individual bacteriochlorophyll
      structures. The surface of the trimer has a hydrophobic region that is modeled as
      the complex being a peripheral membrane protein partially embedded in the
      membrane. A general model is presented for the membrane organization with two of
      the bacteriochlorophyll structures in the membrane and transferring energy to the
      reaction center complex. In this model these two bacteriochlorophyll structures
      serve a similar role to the cofactors of integral membrane light-harvesting
      complexes although the protein structure surrounding the cofactors is
      significantly different for the BChl a protein compared with the integral
      membrane complexes.

PMID- 9268672
TI  - Amide hydrogen exchange and internal dynamics in the chemotactic protein CheY
      from Escherichia coli.
AB  - The backbone internal dynamics of the wild-type 129 amino acid alpha/beta
      parallel protein CheY and its double mutant F14N/P110G are analysed here by the
      hydrogen-exchange method. The F14N mutation is known to stabilise the protein and
      to accelerate refolding while P110G is destabilising and accelerates unfolding.
      We first assigned and characterised the double mutant by nuclear magnetic
      resonance (NMR), to try and discover any possible conformational change induced
      by the two mutations. The main difference between the two proteins is a
      favourable N-capping interaction of the newly introduced Asn14 side-chain at the
      beginning of the first alpha-helix (alpha-helix A). Second, we have measured the
      exchange rates in the wild-type and mutant CheY. In the first case the observed
      protection factors are slightly dispersed around an average value. According to
      their distribution in the structure, protein stability is highest on one face of
      the central beta-sheet, in the surroundings of the main hydrophobic core formed
      by side-chains of residues in beta-strands I, II and III and helices A and E. The
      mutations in the double mutant protein affect two distinct subdomains differently
      (from beta-strand I to III and from alpha-helix C to the end). In the second
      subdomain the number of protected protons is reduced with respect to those in the
      wild-type. This differential behaviour can be explained by a selective decrease
      in stability of the second folding subdomain produced by the P110G mutation and
      the opposite effect in the first subdomain, produced by the F14N mutation. alpha
      Helix A, which is involved together with beta-strands I and III in the folding
      nucleus of CheY, shows the largest protection factors in both proteins.

PMID- 9268673
TI  - New diallelic markers in the HLA region of chromosome 6.
AB  - Diallelic polymorphisms have been identified in the HLA-H gene and the ZNF192
      gene located about 2 megabases centromeric to HLA-H. The three polymorphic sites
      in HLA-H together with the two hemochromatosis mutations in this gene give rise
      to 8 different haplotypes. The three polymorphic sites in ZNF192 give rise to 4
      different haplotypes. The haplotypes in HLA-H are in complete linkage
      disequilibrium with the two common mutations in that gene, 845A (C282Y) and 187G
      (H63D). The 845A mutation is in weak linkage disequilibrium with the ZNF192
      polymorphisms and the 187G mutation appears to be in equilibrium with this
      polymorphism. The 187G mutation therefore appears to be the older of the two HLA
      H mutations.

PMID- 9268674
TI  - Selective interaction of a conformationally-constrained Arg-Gly-Asp (RGD) motif
      with the integrin receptor alphavbeta3 expressed on human tumor cells.
AB  - Two antigenized antibodies (AgAbs) were engineered to express peptidic Arg-Gly
      Asp (RGD) motifs present in extracellular matrix molecules. The RGD tripeptide
      sequence was inserted in the third hypervariable loop of an immunoglobulin
      human/mouse chimeric heavy chain gene as a single or three repeat yielding two
      antibodies termed gamma1RGD and gamma1(RGD)3, respectively. The antibodies were
      used to target specific cell-surface receptors of the integrin type expressed by
      three human tumor cell lines, a melanoma (M21), and osteosarcoma (KRIB) and a
      fibroblastoma (WI-38). Based on in vitro adhesion assays and flow cytometric
      analysis, we found that all three cell lines interacted with gamma1(RGD)3 but not
      with gamma1RGD. Binding of tumor cells to surface-immobilized gamma1(RGD)3 was
      inhibited in a dose-dependent manner by the RGD-containing synthetic peptides
      GdRGDSP and RGDS. These synthetic peptides, but no a GDR-containing control
      peptide, interfered with the binding of tumor cells to surface-immobilized human
      fibronectin. In their soluble form, neither fibronectin nor gamma1(RGD)3
      inhibited tumor cell adhesion to surface-immobilized fibronectin. Gamma1(RGD)3
      specifically recognized integrin alphavbeta3 based on two criteria: reactivity
      with purified integrin receptors and binding to variants of M21 melanoma cells
      expressing alphavbeta3, alphaIIbbeta3 or no beta3 integrins, respectively.
      Collectively, our results indicate that the (RGD)3 loop in the antigenized
      antibody mimics the ligand function of natural extracellular matrix proteins and
      has a restricted receptor specificity for the alphavbeta3 integrin which is not
      inherent to short RGD containing peptides.

PMID- 9268675
TI  - High-level production and isotope labeling of snake neurotoxins, disulfide-rich
      proteins.
AB  - The aim of this work was to produce and to label snake neurotoxins, disulfide
      rich proteins. A mutant of a snake toxin, erabutoxin a, was used as a model. Its
      N-terminal part was fused to ZZ, a synthetic IgG-binding domain of protein A (B.
      Nilsson et al., 1987, Protein Eng. 1, 107-113), thus preventing degradation in
      the bacterial cytoplasm and providing a simple affinity-purification method on
      IgG Sepharose. A soluble fusion protein was obtained with a yield of 60 mg/L,
      corresponding to 20 mg/L toxin. The toxin moiety was folded on the column while
      the hybrid was still bound. The oxidoreducing conditions for the refolding were
      optimized and were found to be oxidative but with a need for reducing molecules.
      The concentration of the hybrid bound to the column could be increased up to 3.3
      mg/ml without significantly altering the folding process. CNBr cleavage of the
      fusion protein followed by a purification step yielded about 2 mg of biologically
      active toxin mutant per gram of dry cell weight. This procedure was applied to
      produce 55 mg of a toxin uniformly labeled with 15N.

PMID- 9268676
TI  - Purification of pregnancy zone protein and its receptor binding domain from human
      plasma.
AB  - A new significantly improved method for purification of pregnancy zone protein
      (PZP), alpha 2-macroglobulin (alpha 2M), and the C-terminal PZP receptor binding
      domain is presented. Several steps in an earlier procedure have been deleted, and
      modifications in the gradients in the DEAE step leave most of the contaminants
      bound to a DEAE-Sephacel gel. This procedure makes possible the rapid,
      simultaneous purification of both of these closely related unstable proteins in
      native form from human plasma, with no thiolester cleavage or formation of
      tetrameric PZP. The final preparations of both alpha 2M and PZP are pure as
      determined by nonreducing and reducing polyacrylamide gel electrophoresis
      following silver staining and no cross-contamination can be observed. The yield
      has been significantly improved and typically more than 500 mg PZP can be
      obtained from 1 liter pregnancy plasma. Furthermore, the stability of PZP at
      different temperatures on storage was studied. In liquid nitrogen PZP can be
      maintained in native dimeric form with intact thiolester for many years. The
      storage of native PZP with intact functional properties during and after
      purification is an obligatory prerequisite to elucidate the biological role of
      PZP. The receptor binding domain of PZP can be cleaved from the PZP-methylamine
      complex by papain and isolated from the other peptides by S-200 gel filtration.
      The cleavage site was determined and the C-terminal fragment was identified with
      several site-specific monoclonal antibodies against PZP.

PMID- 9268677
TI  - High-level expression of soluble protein in Escherichia coli using a His6-tag and
      maltose-binding-protein double-affinity fusion system.
AB  - Using the maltose-binding protein (MBP) fusion vector pMAL-c1 from C. V. Maina et
      al. (1988, Gene 74, 365-373), we have constructed expression vectors which
      contain a sequence encoding six consecutive histidine residues (His6-tag) at the
      3' end of the MBP-encoding malE gene which is followed by either a thrombin
      binding site (LVPRGS) or a factor Xa-binding site (IEGR). The benefits of this
      approach include; (a) high expression levels of soluble MBP fusion proteins
      (exceeding 2% of the total cellular protein), (b) high-quality purification of
      proteins under various conditions (high salt, low salt, denaturing,
      nondenaturing, etc.), and (c) two alternative protease cleavage sites to test for
      the most efficient cleavage of each fusion protein. We also constructed these MBP
      His 6-tag expression vectors with alternative selection markers (Ampr, Kanr) and
      alternative promoters (tac, T7). Using these constructs, we expressed and
      purified several proteins of which we present two, penicillin-binding protein
      PBP2a and UDP-N-acetylmuramate:L-alanine ligase (MurC), and compare their
      expression level and purity with other expression systems. We also discuss the
      use of minimal media with supplements versus rich media and cell growth
      strategies to optimize the protein yield in general and for isotope labeling.

PMID- 9268678
TI  - Low concentration of inducer favors production of active form of 6-phosphofructo
      2-kinase/fructose-2,6-bisphosphatase in Escherichia coli.
AB  - Expression of chicken and rat liver bifunctional enzyme, 6-phosphofructo-2
      kinase/fructose-2,6-bisphosphatase, in Escherichia coli encountered two common
      problems: the chicken enzyme was liable to proteolysis and the rat enzyme was
      prone to form inclusion bodies. Reducing the rate of protein synthesis by
      lowering either growth temperature or isopropyl-beta-D-thiogalactopyranoside
      (IPTG) concentration alleviated these two problems. Growth at 22 degrees C was
      optimum for expression of both enzymes. The optimum range of IPTG concentration
      for expression was 0.1-1 microM for the chicken liver bifunctional enzyme and 10
      microM for rat liver enzyme. The components of growth medium also influenced the
      production. Compared with Luria-Bertani medium, an enriched medium-tryptone
      phosphate medium-tripled the production of the active enzymes. Addition of
      glucose (0.2%) doubled the expression level of active chicken liver enzyme, but
      reduced the production of active rat liver enzyme to half the maximal level,
      while the phosphate in tryptone-phosphate medium had no effect on the production
      of the two enzymes.

PMID- 9268679
TI  - Expression and purification of soluble, active heterodimeric guanylyl cyclase
      from baculovirus.
AB  - A method for expression and purification of active cytosolic heterodimeric
      histidine (His)-tagged guanylyl cyclase of the alpha 1/beta 1 isoform has been
      developed using recombinant baculovirus-transfected insect cells. Confirmation of
      expression of active cyclase was obtained by both Western analysis and enzymatic
      activity. A His tag on the COOH-terminus of the alpha 1 and beta 1 subunits
      allowed rapid purification of the heterodimeric form of guanylyl cyclase in a
      single affinity step using a nickel column. A second gel-filtration step was
      applied to reconstitute into the complex heme, a required cofactor. This was
      confirmed spectroscopically by absorbance in the Soret region. Like enzyme
      purified from tissue, the activity of recombinant guanylyl cyclase was increased
      by protoporphyrin IX and inhibited by both Zn- and Sn-protoporphyrin. The method
      described here should provide a general approach for the expression and
      purification of alternate forms of cytosolic guanylyl cyclase and facilitate
      mechanistic and structural studies of this important family of enzymes.
      Furthermore, the procedure demonstrates the utility of the His-tag system to
      purify multimeric proteins.

PMID- 9268680
TI  - Amino-terminal charge affects the periplasmic accumulation of recombinant
      heregulin/EGF hybrids exported using the Escherichia coli alkaline phosphatase
      signal sequence.
AB  - An Escherichia coli expression system that exploits the bacterial alkaline
      phosphatase (PhoA) signal sequence to translocate recombinant human epidermal
      growth factor (hEGF) to the periplasm was used to evaluate how changes in the
      composition and sequence of amino acids near the PhoA-hEGF junction influence the
      periplasmic accumulation of recombinant protein. A series of chimeric structural
      genes was generated by in vitro replacement of hEGF sequence with analogous
      segments from the EGF-like domain of human heregulin (HRG), significantly
      altering the electrostatic character of the amino-terminal region of the mature
      protein. Quantitation of HRG/EGF protein in E. coli periplasmic extracts, by RP
      HPLC, showed a fourfold decrease after one of two acidic residues located in the
      amino-terminal region of the mature hEGF, near the PhoA junction, was replaced.
      An additional threefold decrease was observed when the second acidic residue was
      replaced with a positively charged lysine. Further extension of the amino
      terminal HRG sequence, beyond the first six residues, resulted in net
      neutralization of a more distant EGF acidic residue with no additional effect on
      protein yield. The importance of having a negatively charged group in the amino
      terminal region of the mature protein was confirmed when insertion of an aspartic
      acid near the amino-terminus of two poorly expressed hybrid protein sequences
      resulted in a five- to eightfold increase in their recovery from the periplasm.
      This study demonstrates the importance of having negatively charged residues near
      the fusion junction of recombinant proteins expressed in E. coli using the PhoA
      signal sequence for protein export.

PMID- 9268681
TI  - Purification of alcohol dehydrogenase from Entamoeba histolytica and
      Saccharomyces cerevisiae using zinc-affinity chromatography.
AB  - We have developed a single-step method for the purification of NADP(+)-dependent
      alcohol dehydrogenase from Entamoeba histolytica and NAD(+)-dependent alcohol
      dehydrogenase from Saccharomyces cerevisiae. It is based on the affinity for zinc
      of both enzymes. The amebic enzyme was purified almost 800 times with a recovery
      of 54% and the yeast enzyme was purified 30 times with a recovery of 100%. The
      kinetic constants of the purified enzymes were similar to those reported for
      other purification methods. With mammalian alcohol dehydrogenase, we obtained a
      40-kDa band suggestive of purified alcohol dehydrogenase, but we failed to retain
      enzymatic activity in this preparation. Our results suggest that the described
      method is more applicable to the purification of tetrameric alcohol
      dehydrogenases.

PMID- 9268682
TI  - Expression of biologically active beta subunit of bovine follicle-stimulating
      hormone in the methylotrophic yeast Pichia pastoris.
AB  - Follicle-stimulating hormone (FSH), a pituitary gonadotropin, is a heterodimer
      composed of an alpha subunit, which is common to all the glycoprotein hormones,
      noncovalently associated with the hormone-specific beta subunit. The objective of
      the present study is to develop a recombinant DNA expression system for the beta
      subunit of FSH that can be applied to study structure-function relationships
      while producing large quantities of the hormone subunit for immuno-contraceptive,
      clinical, and veterinary purposes. We report here the expression of biologically
      active bovine FSH beta (bFSH beta) in the methylotrophic yeast Pichia pastoris.
      The Pichia-expressed FSH beta (pFSH beta) was secreted into the culture medium
      and was found to be immunologically very similar to pituitary-derived ovine FSH
      beta. Replacement of cognate signal peptide with the yeast alpha mating factor
      signal peptide increased the level of expression from 230 ng/ml (cognate signal
      peptide) to 4 micrograms/ml (alpha mating factor signal peptide) of the culture
      supernatant. pFSH beta His.tag (pFSH beta with six histidine residues at the C
      terminus) was purified to apparent homogeneity using one-step nickel affinity
      chromatography. The molecular weight of purified pFSH beta His.tag was
      approximately 22,000, which was slightly higher than that of the pituitary
      derived ovine FSH beta. pFSH beta His.tag could assemble with the alpha subunit
      to yield a heterodimer capable of binding to the FSH receptors and also elicit
      biological response. These data show that pFSH beta His.tag is properly folded
      and biologically active.

PMID- 9268683
TI  - Recombinant uracil phosphoribosyltransferase from the thermophile Bacillus
      caldolyticus: expression, purification, and partial characterization.
AB  - The upp gene encoding the major uracil phosphoribosyltransferase (UPRT) of the
      thermophile Bacillus caldolyticus was cloned by complementation of an Escherichia
      coli upp mutation. The nucleotide sequence of the cloned DNA revealed an open
      reading frame of 630 bp encoding a polypeptide of 209 amino acids (M(r) 22,817)
      with 84% amino acid sequence identity to the deduced upp gene product of Bacillus
      subtilis. Primer extension analysis indicated that the transcriptional start site
      of the cloned gene was positioned 37 or 38 bp upstream of the coding region. When
      over-expressed in E. coli, the recombinant UPRT represented approximately 18% of
      the soluble cellular proteins. The enzyme was purified to homogeneity by two
      sequential precipitations with 50 mM Na-phosphate, pH 7.0. Gel filtration
      chromatography indicated that the native enzyme existed as a dimer at high
      protein concentrations but that it dissociated to a monomeric form on dilution.
      In dilute solutions the enzyme is highly unstable but can be stabilized by
      addition of bovine serum albumin. In concentrated solution (> 5 mg/ml) the enzyme
      is stable for months at 4 degrees C, even in the absence of bovine serum albumin.
      By comparing the UPRT activity of crude extracts of B. subtilis and B.
      caldolyticus it was found that the enzyme from B. caldolyticus was considerably
      more stable toward thermal inactivation than the homologous enzyme from B.
      subtilis.

PMID- 9268684
TI  - Cloning, overexpression, refolding, and purification of the nonspecific
      phospholipase C from Bacillus cereus.
AB  - Bacillus cereus secretes a nonspecific phospholipase C (PLC) that catalyzes the
      hydrolysis of phospholipids to yield diacylglycerol and a phosphate monoester. B.
      cereus PLC has been overexpressed with its signal sequence in Escherichia coli
      using a T7 expression system. The expressed enzyme formed intracellular inclusion
      bodies which were solubilized in the presence of 8 M urea. Renaturation was
      initiated by gradual removal of urea and addition of zinc ions. The signal
      peptide was specifically cleaved by a protease, clostripain, added when the urea
      concentration was 1.5 M. Factors that led to protein reaggregation included rapid
      removal of urea, use of Tris instead of barbital buffer, and presence of the
      signal peptide when the urea concentration was below 1.5 M. The folded protein
      was purified by Q-Sepharose Fast flow chromatography to yield a preparation > 99%
      pure. The final yield of active enzyme was 30-40 mg per liter of culture. The
      recombinant PLC exhibited biochemical and kinetic properties identical to those
      of extracellularly produced PLC from B. cereus. Site-specific mutagenesis of Asn
      134 was carried out as a test of the general effectiveness of the refolding
      procedure.

PMID- 9268685
TI  - Expression, purification, and characterization of recombinant human factor X.
AB  - A system is described for producing recombinant factor X with properties very
      similar to human plasma factor X. Optimization of the expression system for
      factor X resulted in the finding that human kidney cells (293 cells) are superior
      to the widely utilized baby hamster kidney cells (BHK cells) for the expression
      of functional factor X. It was also determined that production of factor X by 293
      cells requires the substitution of the -2 residue (Thr-->Arg) which affords the
      removal of the factor X propeptide. Purification of recombinant and plasma factor
      X is accomplished using a calcium-dependent monoclonal antibody directed against
      the gla domain. The proteins are comparable by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. The rate and extent of activation by the
      factor X coagulant protein from Russell's viper venom and by factors IXa and
      VIIIa are similar; activation of the recombinant protein by VIIa and tissue
      factor is mildly faster. The activated enzymes have the same activity toward a
      chromogenic substrate and the biologic substrate, prothrombin. Both enzymes have
      the same apparent affinity for the activated platelet surface as judged by their
      ability to activate prothrombin. Finally, inhibition by antithrombin, with or
      without heparin, and inhibition by the tissue factor pathway inhibitor are
      equivalent. Recombinant factor X produced by this method is therefore well suited
      for probing structure-function relationships by mutational analysis.

PMID- 9268686
TI  - High-level expression and purification of a recombinant human alpha-1, 3
      fucosyltransferase in baculovirus-infected insect cells.
AB  - A human alpha-1,3-fucosyltransferase (Fuc-TVII) was expressed by recombinant
      baculovirus-infected insect Sf9 cells as a secretory fusion protein. The fusion
      protein consisted of the human granulocyte colony-stimulating factor signal
      peptide followed by an IgG-binding domain of protein A, a Fuc-TVI-derived
      peptide, and the putative catalytic domain of Fuc-TVII. The signal peptide was
      correctly cleaved and the recombinant Fuc-TVII was secreted into the culture
      medium at a concentration of 10 micrograms/ml. The recombinant Fuc-TVII could be
      highly purified in a single-step purification procedure, i.e., IgG-Sepharose
      column chromatography. The enzymatic properties of the Sf9-produced Fuc-TVII were
      compared with the properties of that expressed by a human B-cell line, Namalwa
      KJM-1, transfected with an episomal plasmid carrying the fusion Fuc-TVII cDNA.
      Both recombinant proteins showed alpha-1,3-fucosyltransferase activity toward a
      type II oligosaccharide with a terminal alpha-2,3-linked sialic acid among
      various acceptors. The apparent Km values of Sf9-produced Fuc-TVII for GDP-fucose
      and its acceptor substrate were slightly lower than those of the Fuc-TVII
      produced by Namalwa KJM-1 cells. Sf9-produced Fuc-TVII has N-linked carbohydrate
      chains whose molecular weights are lower than those linked to Namalwa KJM-1
      produced Fuc-TVII. This difference in carbohydrate structure hardly affects the
      thermal stability of Fuc-TVII. The baculovirus expression system is available for
      high-level expression of stable and enzymatically active secretory Fuc-TVII.

PMID- 9268687
TI  - Direct demonstration of the bifunctional property of Tetrahymena 14-nm filament
      protein/citrate synthase following expression of the gene in Escherichia coli.
AB  - Tetrahymena 14-nm filament protein/citrate synthase (49K protein) is a
      bifunctional protein with roles in the cytoskeleton and as a citrate synthase.
      Though previous studies have shown that the 49K protein is derived from a single
      transcript of a single gene, direct demonstration of the 49K protein's
      bifunctional property remained to be elucidated. In this study, a recombinant 49K
      protein was expressed in Escherichia coli, purified and characterized. The
      citrate synthase activity of the recombinant 49K protein was comparable to that
      of the 49K protein purified from Tetrahymena. The recombinant 49K protein formed
      14-nm filaments, but only of short length. The filaments were elongated in the
      presence of a soluble fraction of Tetrahymena. These results suggest that the 49K
      protein itself is bifunctional, but some co-factor(s) is necessary for elongation
      of filaments.

PMID- 9268688
TI  - Effect of vitamin A deficiency on the expression of low affinity glucocorticoid
      binding site activity and glucocorticoid-dependent induction of CYP3A2 in rat
      liver.
AB  - Maintenance of rats on a vitamin A-deficient diet resulting in undetectable
      levels of plasma retinol and significant reductions in relative testes weight
      compared to age-matched controls leads to the loss of liver membrane-bound low
      affinity glucocorticoid binding site (LAGS) activity without any effects on the
      levels of constitutively expressed CYP3A2 protein. Subsequent daily
      administration of retinol acetate to vitamin A-deficient rats results in the re
      expression of LAGS activity to control levels by 7 days. To determine any role
      for the LAGS in the modulation of CYP3A2 expression by glucocorticoids, a single
      dose of dexamethasone 21-phosphate was administered to vitamin A-deficient rats
      and vitamin A-deficient rats induced to re-express LAGS by daily retinol acetate
      treatment. Retinol acetate administration alone induces CYP3A2 protein to
      apparent maximal levels since dexamethasone 21-phosphate does not further
      increase the induction response. However, CYP3A2 remains inducible to
      dexamethasone 21-phosphate in vitamin A-deficient rats. These data suggest that
      vitamin A status affects the expression of LAGS and CYP3A2 but that
      glucocorticoids regulate the induction of CYP3A2 by a mechanism(s) independent of
      their interaction with the LAGS.

PMID- 9268689
TI  - Decreased CP-1 (NF-Y) activity results in transcriptional down-regulation of
      topoisomerase IIalpha in a doxorubicin-resistant variant of human multiple
      myeloma RPMI 8226.
AB  - Decreased topoisomerase II (Topo II) activity results in resistance to
      antineoplastic agents targeting this enzyme. Dox1V derived from human multiple
      myeloma RPMI 8226 demonstrated a 4-fold resistance to doxorubicin in the absence
      of MDR1 overexpression or topo II mutations (Futscher B.W., Foley N., Gleason
      Guzman M., Meltzer P.S., Sullivan D.M., and Dalton W.S., Int'l. J. Cancer, 66:
      520-5, 1996.). Consistent with its drug resistant phenotype, a 2- to 3-fold
      decrease in topo II expression was identified. To investigate the molecular basis
      for decreased topo II expression in Dox1V, a semi-quantitative analysis of Topo
      II activity, protein level and mRNA transcript were performed. The results
      demonstrated that reduced Topo II activity is due to a decreased mRNA level.
      Southern blot and sequencing experiments revealed wild-type sequence of the topo
      II promoter in the drug resistant cells. Transient gene expression assays
      demonstrated that topo II is transcriptionally down-regulated in Dox1V
      independent of the promoter sequence of the endogenous alleles. Instead, the
      activity of a ubiquitous transcription factor CP-1 (NF-Y) interacting with the
      topo II promoter is decreased. The decrease in CP-1/NF-Y activity in Dox1V is
      correlated well with the decrease in topo II transcriptional activity, transcript
      level, Topo II protein and enzyme activity. Therefore, transcriptional down
      regulation resulted from a reduced CP-1/NF-Y activity is responsible for
      decreased topo II expression in Dox1V cells.

PMID- 9268690
TI  - Electrical stimulation induces the level of TGF-beta1 mRNA in osteoblastic cells
      by a mechanism involving calcium/calmodulin pathway.
AB  - It is well-known that electrical stimulation can prompt healing of bone
      fractures. However, the mechanism involved is less clear. In this study, we found
      that capacitively coupled electric field-induced proliferation of osteoblastic
      cells (MC3T3-E1) accompanied increased levels of transforming growth factor-beta
      1 (TGF-beta1) mRNA determined by quantitative reverse transcription/polymerase
      chain reaction. Previous reports have shown that verapamil and W-7, both of which
      block voltage gated calcium channels and inhibit the activation of cytosolic
      calmodulin, respectively, blocked capacitively coupled electric field-induced
      proliferation of the osteoblast cells. Interestingly, we found that verapamil and
      W-7 can also block capacitively coupled electric field-induced elevation of TGF
      beta1 mRNA. This result suggested that electrical stimulation induces the level
      of TGF-beta1 mRNA in osteoblastic cells by a mechanism involving
      calcium/calmodulin pathway. The potential roles of TGF-beta in the electrical
      signal-induced osteogenesis was discussed.

PMID- 9268691
TI  - ZBP-89, a Kruppel-type zinc finger protein, inhibits cell proliferation.
AB  - ZBP-89 is a Kruppel-type zinc finger transcription factor that binds to GC-rich
      sequences. Overexpression of this factor prevents EGF induction of the gastrin
      promoter; therefore, we postulated that ZBP-89 may modulate cellular
      proliferation. To test this hypothesis, ZBP-89 was overexpressed in immortalized
      (GH4) and malignant (AGS) cell lines. Growth parameters, e.g., 3H-thymidine, BrdU
      labeling, flow cytometry and ornithine decarboxylase promoter activity were
      analyzed. The results show that DNA synthesis is inhibited and progression to S
      phase is blocked in GH4 cells. Collectively, these studies demonstrate that ZBP
      89 inhibits cellular proliferation at least in part through its ability to bind
      and repress ornithine deacarboxlyase promoter activity.

PMID- 9268692
TI  - Identification of Goalpha, Gqalpha, and Gsalpha immunoreactivity associated with
      the rat pancreatic zymogen granule membrane.
AB  - In this study we have determined which Galpha proteins are associated with the
      pancreatic zymogen granule membrane. The purity of the granule preparation was
      evaluated both morphologically and biochemically. These studies demonstrated that
      the isolated zymogen granules were free of any significant cross contamination
      from other organelles including the plasma membrane. Western blot analysis showed
      that Goalpha, Gqalpha, and Gsalpha are associated with the zymogen granule
      membrane, but that Gi1alpha, Gi2alpha, and Gi3alpha are not. The location of
      these Galpha proteins suggests that they may modulate regulated exocytosis in the
      pancreatic acinar cell.

PMID- 9268693
TI  - Activation of JNK/SAPK and ERK by mechanical strain in vascular smooth muscle
      cells depends on extracellular matrix composition.
AB  - Application of cyclic mechanical strain to vascular smooth muscle (VSM) cells
      elicits distinct cellular responses depending on extracellular matrix
      composition. We now examine activation of p42/p44 MAP kinase (ERK) and c-jun
      amino terminal kinase (JNK/SAPK) by cyclic (1 Hz) mechanical strain in neonatal
      rat VSM cells cultured on pronectin or laminin. In cells grown on pronectin,
      mechanical strain activated both ERKs (peak 10-30 min) and JNK/SAPK (peak 15-30
      min). On laminin, mechanical strain induced a comparable activation of JNK/SAPK
      to that seen on pronectin, but no significant activation of ERKs. In contrast,
      application of strain to adult VSM cells activated both enzymes independently of
      extracellular matrix composition. In neonatal VSM cells, cyclic strain induced SM
      1 smooth muscle myosin in cells cultured on laminin, but not on pronectin.. Thus
      in neonatal VSM cells, activation of ERKs and induction of SM-1 myosin by
      mechanical strain depend on extracellular matrix composition.

PMID- 9268694
TI  - Interaction of DA41, a DAN-binding protein, with the epidermal growth factor-like
      protein, S(1-5).
AB  - Recently, we have identified a new protein (DA41) which can associate with
      candidate tumor-suppressor DAN protein. In the present study, we have searched
      for DA41-interacting protein(s), using a yeast two-hybrid system. An adult rat
      lung cDNA library was screened by using a truncated form of DA41 (1-308) which
      lacks a DAN-binding region as bait. One of the positive clones, T16, contained a
      cDNA sequence of 1934 nucleotides with a single open reading frame of 493 amino
      acids. A data base search revealed that T16 exhibited a strong sequence
      similarity to the human epidermal growth factor (EGF)-like protein, S(1-5). The
      region encoding amino acids 155-232 of DA41 was identified for the interaction
      with T16. Since DAN and S(1-5) proteins are known to suppress and stimulate DNA
      synthesis, respectively, it is possible that functional interaction of DAN with
      S(1-5) through DA41 might play an important role(s) in the regulation of cell
      growth.

PMID- 9268696
TI  - Bradykinin induces actin reorganization and enhances cell motility in HaCaT
      keratinocytes.
AB  - In HaCaT keratinocytes bradykinin-triggered actin reorganization was inhibited by
      quinacrine, a phospholipase A2 inhibitor, and restored by addition of arachidonic
      acid. Bradykinin-induced actin breakdown and cortical actin formation were
      respectively prevented by indomethacin, a cyclooxygenase inhibitor, and
      nordihydroguaiaretic acid, a lipoxygenase inhibitor. Addition of prostaglandins
      or leukotrienes, respectively, reversed the effects of inhibitors. This suggested
      a crucial role for a cyclooxygenase product in actin depolymerization and for a
      lipoxygenase product in cortical actin formation. Furthermore, we found that
      bradykinin stimulated HaCaT keratinocyte migration. This event was blocked by
      quinacrine, indomethacin or nordihydroguaiaretic acid, and restored by addition
      of prostaglandins or leukotrienes, respectively. We also showed that genistein, a
      tyrosine kinase inhibitor, inhibited HaCaT cell locomotion. In conclusion,
      bradykinin modulated actin reorganization and cell motility in keratinocytes,
      probably by a mechanism involving arachidonic acid metabolites and a tyrosine
      kinase activity.

PMID- 9268695
TI  - Phorbol ester-induced sensitisation of adenylyl cyclase type II is related to
      phosphorylation of threonine 1057.
AB  - Following up the results from previous studies on chemical fragmentation of TPA
      treated, [32P]phosphate labeled adenylyl cyclase type II (AC II) (Bol, G. F.,
      Hulster, A., and Pfeuffer, T. in press) we have replaced serine 871 or threonine
      1057 by alanine using site directed mutagenesis. Both mutants had unimpaired
      catalytic activity, however enhancement by phorbolester TPA was reduced by 60-80
      % in the T1057A mutant, but not in the S871A mutant. The stimulation of adenylyl
      cyclase type II by betagamma subunits of heterotrimeric G-pro teins and that by
      PKC have been previously shown to be mutually exclusive (Zimmermann and Taussig
      (1996), J. Biol. Chem. 271, 27161-27166). This is in line with the present
      findings that AC II expressed in COS-1 cells was only barely stimulated (10%) by
      coexpressed betagamma-subunits in presence of TPA. Mutation of threonine 1057 to
      alanine however caused partial regain of betagamma-stimulation in the presence of
      TPA by 40%, as compared to that of WT adenylyl cyclase type II which was 70% in
      the absence of TPA. These data strongly implicate the importance of threonine
      1057 as phosphate acceptor following PKC-mediated sensitisation of adenylyl
      cyclase type II.

PMID- 9268697
TI  - Sulfated lipids as inhibitors of pancreatic trypsin and chymotrypsin in
      epithelium of the mammalian digestive tract.
AB  - Cholesterol sulfate and I3SO3-GalCer, which were commonly contained in the
      epithelia of mammalian digestive tracts, were found to inhibit the activities of
      typical digestive enzymes, pancreatic trypsin and chymotrypsin, but steroid
      sulfates, gangliosides and the other membrane constituents did not show any
      inhibitory activity. The preincubation of trypsin with I3SO3-GalCer at 37 degrees
      C for 10min was necessary to inhibit the activity of trypsin, but cholesterol
      sulfate showed its inhibitory activity without preincubation. Sulfated lipid
      treated enzyme gave the same Km as and lower Vmax than those of the original
      enzymes. Also, both sulfated lipids inhibited pronase from Streptomyces griseus,
      but not lysyl endopeptidase from Achromobacter lyticus. These findings indicate
      that cholesterol sulfate and I3SO3-GalCer in the digestive tract function as
      epithelial inhibitors to prevent tissue injury by endogenous and exogenous
      proteases.

PMID- 9268698
TI  - The epitope recognized by a monoclonal antibody in the myelin-associated protein
      CNP.
AB  - The epitope recognized by a monoclonal antibody (MAb-46-1) directed against the
      myelin-associated protein CNP (2',3'-cyclic nucleotide 3'-phosphodiesterase; EC
      3.1.4.37) from several species was characterized. MAb-46-1 can be employed for
      immunoprecipitation, immunostaining in Western blots and in immunohistochemistry.
      Short peptides derived from the human CNP1 peptide sequence were synthesized and
      used in enzyme linked immunosorbent assays to test the reactivity of MAb-46-1.
      Coarse screening experiments enabled us to localize the epitope recognized by MAb
      46-1 to the amino acid residues 9 to 19 close to the N-terminus. Further
      investigations using shorter peptides comprising this part of the protein allowed
      us to identify a 9 amino acid residue long peptide (amino acids 11 to 19:
      ELQFPFLQD) which represents the minimal epitope recognized by MAb-46-1, probably
      through a 3-dimensional structure and less likely a straight linear peptide. The
      epitope seems to be stabilized also by the attached amino acids 7 to 10 (KDKP).
      The peptide sequence 9-19 is conserved in all CNP sequences described so far.
      Thus, MAb-46-1 might be of general usefulness for further studies of the not yet
      identified function of the myelin-associated protein CNP.

PMID- 9268699
TI  - Oxidized LDL binding to a macrophage-secreted extracellular matrix.
AB  - Extracellular matrix (ECM), which was shown to be secreted by arterial wall
      cells, is a major part of the atherosclerotic lesion. ECM can contribute to low
      density lipoprotein (LDL) retention which can then lead to macrophage foam cell
      formation, the hallmark of early atherogenesis. The present study demonstrated
      that in addition to the known ability of endothelial cells and smooth muscle
      cells to produce ECM, macrophages can also secrete an ECM layer. The macrophage
      derived ECM was shown to contain the proteoglycans chondroitin sulfate, heparan
      sulfate and dermatan sulfate. Macrophage derived ECM can bind native LDL, as well
      as oxidized LDL (3 fold more than native LDL), and this binding is significantly
      increased in the presence of lipoprotein lipase. Glycosaminoglycans from the ECM
      (mainly chondroitin sulfate and heparan sulfate) participate in the binding of Ox
      LDL to the macrophage derived ECM. These observations suggest that ECM is
      produced also by macrophages, and it can contribute to a specific and local
      delivery of atherogenic LDL to macrophages, leading to cellular cholesterol
      accumulation and foam cell formation.

PMID- 9268700
TI  - Effect of heat-induced structural perturbation of secondary and tertiary
      structures on the chaperone activity of alpha-crystallin.
AB  - alpha-Crystallin, a major protein of the lens, is known to have chaperone
      activity to protect other proteins against thermal aggregation. Heat-induced
      structural change of alpha-crystallin was previously shown to increase its
      chaperone activity. In this report, we studied the thermal reversibility of alpha
      crystallin and the effect of change in secondary structure on its chaperone
      function in vitro. The heat-induced conformational changes in the aromatic region
      of near-UV CD spectra showed only a small degree of reversibility. The structural
      transitions from 50 to 70 degrees C were largely reversible if the incubation
      time was short. However, the protective ability to inhibit thermal aggregation of
      alcohol dehydrogenase by alpha-crystallin was essentially similar at 48 and 70
      degrees C. Under long-term heating at high temperatures, there was a time
      dependent irreversibility of structural change in alpha-crystallin as revealed by
      CD spectroscopy. Such denatured alpha-crystallin by long-term heating can still
      preserve its ability to prevent UV-induced aggregation of gamma-crystallin at
      room temperature, indicating relatively little effect of heat-induced changes in
      secondary structure on the chaperone activity of alpha-crystallin.

PMID- 9268701
TI  - Molecular cloning and chromosomal mapping of olfactory receptor genes expressed
      in the male germ line: evidence for their wide distribution in the human genome.
AB  - Olfactory receptor genes constitute the largest family of G protein-coupled
      receptors. We have previously shown that members of this family are expressed
      during spermatogenesis, and that the corresponding proteins are displayed on
      mature sperm cells. In each mammalian species, a restricted subset of olfactory
      receptors is expressed in male germ cells and displays a pattern of expression
      suggestive of their potential implication in the control of sperm physiology. In
      addition to the cDNA fragments available previously, we now report the molecular
      cloning of two olfactory receptor cDNAs from a human testis library. Five
      olfactory receptor genes expressed in germ cells were localized in the human
      genome by radiation hybrid mapping. Three of the genes map to the short arm of
      chromosome 19 (19p13.1-19p31.3), one to chromosome 11 (11q22.1-22.3), and one to
      chromosome 17 (17q21-22). The former two localizations fall within clusters
      previously identified for members of the putative olfactory receptor gene family
      expressed in olfactory mucosa. Similarly, sequence analysis has revealed that
      these testicular genes share no distinctive structural features from the other,
      non-testicular, members of the family. The expression of a subset of olfactory
      receptor genes in the male germ line is therefore not correlated to their
      belonging to a specific structural subgroup, or to a specific gene cluster or
      chromosomal segment.

PMID- 9268702
TI  - Plus- and minus-stranded hepatitis G virus RNA in liver tissue and in peripheral
      blood mononuclear cells.
AB  - Hepatitis G virus (HGV), which was recently identified, is a single, plus
      stranded RNA virus that is thought to replicate via minus-stranded RNA, but no
      information is available about the distribution of either plus- (genomic) or
      minus- (replicative) stranded HGV RNAs in HGV infected patients. We, therefore,
      tested the serum, liver tissue, and peripheral blood mononuclear cells (PBMCs) of
      six hepatitis patients with HGV infection for the presence of plus- and minus
      stranded HGV RNA. The RT-nested PCR was used with primers derived from 5'
      noncoding region of the genome. Before RT-PCR analysis, the 3'-termini of RNA
      specimens were chemically modified to discriminate between plus- and minus
      stranded HGV RNA. Plus-stranded HGV RNA was detected in the serum and liver
      tissue of all six patients and in the PBMCs of five patients. Minus-stranded RNA
      was detected in the liver tissue of all six patients, in the serum of two
      patients, and in the PBMCs of one patient. In summary, the detection of minus
      stranded HGV RNA in liver tissue may indicate that HGV replicates in the liver.

PMID- 9268703
TI  - Induction of subcutaneous tissue fibrosis in newborn mice by transforming growth
      factor beta-simultaneous application with basic fibroblast growth factor causes
      persistent fibrosis.
AB  - To establish an appropriate animal model of skin fibrosis by exogenous
      application of growth factors, we investigated the in vivo effects of
      transforming growth factor-beta by injection into subcutaneous tissue of newborn
      mice. Histological examination revealed that TGF-beta1, beta2, and beta3 induced
      granulation tissue formation after 3 days of injection, while these changes had
      disappeared after 7 days. The changes after 3 days of injection were more
      pronounced in the tissue injected with TGF-beta2 or beta3 than that with TGF
      beta1. In situ hybridization analysis indicated that connective tissue growth
      factor mRNA was strongly expressed in the fibroblasts at the site of TGF-beta
      injection, which suggested that fibroblasts were activated by TGF-beta. Next, we
      investigated the cooperative effects of TGF-beta and other growth factors
      including basic fibroblast growth factor (bFGF). The simultaneous application of
      TGF-beta and bFGF caused apparent tissue fibrosis which persisted for at least 2
      weeks, while bFGF alone caused slight fibrotic changes after 7 days of injection.
      Thus, we succeeded in establishing an animal model of skin fibrotic disorders by
      the exogenous addition of growth factors, and this animal model will be useful
      for future studies in this area.

PMID- 9268704
TI  - Cloning of P2Y6 cDNAs and identification of a pseudogene: comparison of P2Y
      receptor subtype expression in bone and brain tissues.
AB  - Cellular responses to ATP/UTP and analogs are mediated by G-protein coupled P2Y
      receptors and have been proposed to play a role in the regulation of bone
      metabolism. Using a degenerate PCR approach on MG-63 cell cDNA we found PCR
      fragments coding for human P2Y1 and a new receptor, P2Y6. cDNA cloning of the
      P2Y6 receptor identified three cDNA isoforms. Two contained the same contiguous
      ORFs but differed in their 5' UTRs and may therefore originate by alternative
      splicing whereas the third represents a pseudogene. Analysis of P2Y receptor
      subtype expression in human bone and the osteoblastic cell lines OHS-4 and MG-63
      by RT-PCR showed that all known human P2Y receptor subtypes (P2Y1, P2Y2, P2Y4,
      P2Y6, and P2Y7) were expressed. In contrast, analysis of brain-derived cell lines
      suggests that a selective expression of P2Y receptor subtypes occurs in brain
      tissue.

PMID- 9268705
TI  - Characterization of AT-1 cardiomyocytes as a model for studies of T3 effects on
      cardiac cells.
AB  - AT-1 cardiomyocyte derive from atrial tumors in transgenic mice. Earlier studies
      have indicated a highly differentiated, contracting, cardiac phenotype in primary
      cultures and the AT-1 cardiomyocyte may thus be an excellent in vitro model in
      cardiac research. Thyroid hormone (T3) has positive inotropic and chronotropic
      effects and is clinically known to be relevant in various pathological heart
      conditions. Thyroid Hormone Receptors (TR) are ligand regulated transcriptional
      activators who mediate the effects of T3. The aim of this study was to determine
      whether AT-1 cardiomyocytes express TR. Regular binding competition assays showed
      a Kd of 370 +/- 105 for 125I-T3 binding to TR. Reverse transcription-PCR in mouse
      showed that TRalpha1, alpha2, beta1 and beta2 mRNA were expressed in AT-1
      cardiomyocytes and mouse myocardium. Western blot with polyclonal rabbit
      antibodies against human TR revealed the presence of TRalpha1, beta2 and low
      levels of TRbeta1 while TRalpha2 was not detectable. Generally, for the detected
      subtypes the intensities of the bands were weaker for AT-1 cardiomyocytes in
      comparison to mouse heart. We conclude that the AT-1 cardiomyocytes express both
      protein and mRNA for TR and may provide a useful model for studying T3 effects in
      cultured cardiac myocytes.

PMID- 9268706
TI  - Differential display cloning of a novel rat cDNA (RNB6) that shows high
      expression in the neonatal brain revealed a member of Ena/VASP family.
AB  - We have used the differential display method to identify genes that control the
      neural cell development in CNS. Screening of the differential display bands that
      showed higher expression at neonate than at adult age enabled us to identify a
      novel rat cDNA (RNB6) coding for a protein of 393 amino acid residues. Database
      search revealed this gene as a rat homologue of the murine EVL, a member of
      Ena/VASP protein family that is implicated to be involved in the control of cell
      motility through actin filament assembly by their GP5 motifs. Although the
      precise characterization of EVL was not reported, our Northern blot and
      immunoblot analyses demonstrated that RNB6 expression in the brain gradually
      increases during embryonic development, reaches maximum at postnatal day 1 and
      decreases thereafter. Studies of tissue distribution revealed the expression of
      RNB6 not only in the brain but also in the spleen, thymus and testis.
      Histochemical analyses showed that RNB6 protein is mainly expressed in neurons
      and may be expressed in neural fibers. Our analyses suggest that RNB6 is
      critically involved in the development of CNS probably through the control of
      neural cell motility and/or including neuronal fiber extension.

PMID- 9268707
TI  - Bidirectional regulation of telomerase activity in a subline derived from human
      lung adenocarcinoma.
AB  - Telomerase is active in germline cells and tumor cells, but is either not
      expressed or is repressed in a majority of somatic cells. The regulation
      mechanism of telomerase activity has lately drawn considerable attention for the
      possible use of telomerase inhibitors for anti-cancer therapy. We analyzed the
      regulation mechanism of telomerase activity in the human lung adenocarcinoma cell
      line A549 and its subline A5DC7 which shows impaired tumor phenotypes. Although
      A549 and A5DC7 cells have similar growth potentials, when cultured in medium
      supplemented with 5% fetal bovine serum A5DC7 cells demonstrated a remarkable
      negative regulation of telomerase activity and telomere shortening. After the
      long-term culture, A5DC7 cells showed a large senescent cell-like morphology,
      arrested growth at the 106 population doubling level and entered senescence which
      was demonstrated by expression of the beta-galactosidase senescence marker. When
      the serum concentration was raised from 5% to 10% for the senescent A5DC7 cells,
      telomerase reactivation and telomere lengthening occurred as well as resumption
      of proliferation. These results demonstrate that the growth arrest seen in
      senescent A5DC7 cells is reversible and that telomerase activity is also bi
      directionally regulated in A5DC7 cells, an event which could not be observed in
      normal senescent cells. This indicates that stringent telomerase repression and
      complete growth arrest concomitant with cellular senescence is collapsed in
      senescent A5DC7 cells in response to exogenous signals. Our study suggests that
      cellular senescence progresses and/or is regulated at multiple levels.

PMID- 9268708
TI  - A transgenic mouse line that retains Cre recombinase activity in mature oocytes
      irrespective of the cre transgene transmission.
AB  - The Cre/loxP site-specific recombination system derived from bacteriophage P1
      provides a convenient tool for directed modifications of genomes in various
      organisms. To exploit Cre-mediated manipulation of mouse genomic sequences at the
      zygote stage, we have developed a transgenic mouse line carrying the CAG-cre
      transgene in which the cre gene is under control of the cytomegalovirus immediate
      early enhancer-chicken beta-actin hybrid (CAG) promoter. The activity of the Cre
      recombinase at early stages of development was examined by crossing the CAG-cre
      transgenic mice to another transgenic mouse line carrying a reporter gene
      construct, CAG-CAT-Z, which directs expression of the E. coli lacZ gene upon Cre
      mediated excision of the loxP-flanked chloramphenicol acetyltransferase (CAT)
      gene located between the CAG promoter and the lacZ gene. PCR-based analysis of F1
      progeny from CAG-cre males x CAG-CAT-Z females showed that transmission of the
      CAG-cre transgene was accompanied by the complete deletion of the CAT gene of the
      CAG-CAT-Z transgene in all tissues, and that this deletion was never observed in
      the progeny without transmission of the CAG-cre gene. On the other hand, analysis
      of F1 mice from CAG-CAT-Z males x CAG-cre females showed that the CAG-CAT-Z
      transgene had undergone complete deletion of the CAT gene in all tissues
      irrespective of the cotransmission of the CAG-cre gene. This Cre-mediated
      recombination in F1 mice occurred before the two-cell stage of embryonic
      development, as shown by X-gal staining. The results suggest that the CAG-cre
      transgene is expressed in developing oocytes of CAG-cre transgenic mice, and Cre
      mRNA and/or protein are retained in mature oocytes irrespective of the
      transmission of the CAG-cre transgene, resulting in efficient Cre-mediated
      recombination of paternally derived target genes upon fertilization. The CAG-cre
      transgenic mouse should serve as a useful tool to introduce prescribed genetic
      modifications into the mouse embryo at the zygote stage.

PMID- 9268709
TI  - Limited in vivo proteolysis of aggregated proteins.
AB  - Degradation pathways of insoluble proteins have been analyzed in Escherichia coli
      by using a N-terminal beta-galactosidase fusion protein (VP1LAC) that aggregates
      immediately after its synthesis. In recombinant E. coli cells, lower molecular
      mass products, antigenically related to the entire fusion, accumulate together
      with the entire fusion. In absence of protein synthesis, the insoluble intact
      protein declines, suggesting that degradation of the recombinant protein also
      affects aggregated protein. Time course analysis of both soluble and insoluble
      cell fractions has revealed a limited proteolysis of the insoluble protein that
      removes the heterologous domain and permits the resulting beta-galactosidase
      fragments to refold and solubilize. Further extensive degradation occurs
      exclusively on soluble protein. The restricted proteolysis of misfolded,
      insoluble protein is the initiating event of a subsequent degradative pathway in
      which rate-limiting steps permit the accumulation of stable degradative
      intermediates.

PMID- 9268710
TI  - Selective interaction of protein kinase FA/glycogen synthase kinase-3alpha with
      membrane phospholipids.
AB  - Previously we reported that the activity of protein kinase FA/glycogen synthase
      kinase-3alpha (kinase FA/GSK-3alpha) can be detected in several brain membrane
      fractions. In this report, we examined whether kinase FA/GSK-3alpha can directly
      interact with membrane phospholipids by using anti-kinase FA/GSK-3alpha antibody
      as a more specific studying tool. It was found that kinase FA/GSK-3alpha can
      associate with NaOH-extracted brain membranes and selectively interact with
      several kinds of reconstituted phospholipid vesicles including phosphatidic acid
      (PA), phosphatidyl ethanolamine (PE), phosphatidyl inositol (PI), and
      phosphatidyl serine (PS) vesicles. Increasing ionic strength in the reaction
      could disrupt the interaction between kinase FA/GSK-3alpha and PA, PI, or PE
      vesicles but had no effect on the interaction between kinase FA/GSK-3alpha and PS
      vesicles, indicating that both ionic and non-ionic interactions are involved in
      this process, respectively. Moreover, both kinase activity and protease
      sensitivity of kinase FA/GSK-3alpha can be affected profoundly by these
      phospholipid vesicles and different forms of the kinase can be produced when it
      binds to distinct types of phospholipid vesicles. Taken together, the results
      demonstrate a direct interaction of kinase FA/GSK-3alpha with membrane
      phospholipids and suggest that membrane phospholipids may be directly involved in
      regulating kinase FA/GSK-3alpha activity.

PMID- 9268711
TI  - Phorbol ester effects in atypical protein kinase C zeta overexpressing NIH3T3
      cells: possible evidence for crosstalk between protein kinase C isoforms.
AB  - To examine whether multiple protein kinase C (PKC) isoforms could interact or
      crosstalk, phorbol ester-insensitive atypical PKC (aPKC) zeta isoform was
      overexpressed in NIH3T3 cells, and the cells were stimulated with phorbol ester
      to activate diacylglycerol-dependent conventional (cPKC) and novel PKC (nPKC)
      isoforms. Treatment of cells with phorbol ester which activates PKCalpha, gamma,
      delta, and epsilon isoforms in NIH3T3 cells significantly reduced proliferation
      of cells. Overexpression of aPKCzeta and subsequent phorbol ester treatment
      abolished phorbol ester-induced reduction in cell proliferation. Overexpression
      of aPKCzeta also potentiated phorbol ester-induced mitogen-activated protein
      (MAP) kinase activation in a PKC-dependent manner. The effects of PKCzeta
      overexpression on proliferation and MAP kinase activation were proportional to
      the levels of aPKCzeta expression. Since aPKCzeta cannot be activated by phorbol
      ester, modulation of cell proliferation and MAP kinase activation by phorbol
      ester in aPKCzeta overexpressing cells might be due to the activation of cPKCs
      and/or nPKCs by phorbol ester. Thus, the results provide possible evidence for
      either direct or indirect crosstalk between PKC isoforms.

PMID- 9268712
TI  - Tetrahydrobiopterin regulates superoxide and nitric oxide generation by
      recombinant endothelial nitric oxide synthase.
AB  - Nitric oxide (NO) produced by the endothelial isoform of nitric oxide synthase
      (NOS III) is a key determinant of the anti-atherosclerotic properties of the
      endothelium. Recent in vivo studies suggest that NOS III may also be a source of
      superoxide production, which would limit its role as a NO-producing enzyme. In
      the current study we examined both the NO and the superoxide generating potential
      of recombinant NOS III obtained from a baculovirus/Sf9 expression system. Using
      lucigenin chemiluminesence we could indeed demonstrate (superoxide dismutase
      inhibitable) superoxide production by NOS III. This superoxide production was not
      affected by administration of L-arginine, but could be inhibited dose-dependently
      by the co-factor tetrahydrobiopterin (BH4). BH4 also dose dependently decreased
      superoxide generation by hypoxanthine/xantine oxidase suggesting a direct
      antioxidant effect. Superoxide generation by NOS III could be completely
      inhibited by diphenyleneiodonium (DPI), an inhibitor of the flavin moiety of the
      enzyme, indicating that this group is a main source of superoxide production by
      the enzyme. Using measurement of [3H-L-arginine] conversion to [3H-L-citrulline],
      it appeared that BH4 directly increased the production of NO by NOS III. In
      addition, we observed that BH4 stablized the NOS III in its dimeric form,
      suggesting that an effect on allosteric conformation could be involved in this
      effect on NO production. NOS III thus appears to be a superoxide generating
      enzyme probably through its flavin moiety, as well as a BH4-dependent NO
      producing enzyme.

PMID- 9268713
TI  - Functional importance of heat shock protein 90 associated with insulin receptor
      on insulin-stimulated mitogenesis.
AB  - The role of stress proteins on the function of insulin receptor is not well
      understood. In the rat-1 fibroblasts overexpressing human insulin receptors, heat
      shock protein (Hsp) 90 was co-immunoprecipitated with insulin receptors and the
      association was not affected by insulin stimulation. A GST-fusion protein
      containing the intracellular insulin receptor beta subunit was associated with
      Hsp 90 in vitro, suggesting the direct interaction of this protein with insulin
      receptor beta-subunit. Furthermore, microinjection of anti-Hsp 90 antibody into
      these cells completely inhibited insulin-stimulated mitogenesis. However, neither
      epidermal growth factor-stimulated nor serum-stimulated mitogenic signal in the
      cells was affected by the antibody microinjection. These results suggest that Hsp
      90 constitutively binds to insulin receptor beta-subunit, which may be necessary
      for insulin signaling in mitogenesis.

PMID- 9268714
TI  - Autocrine growth regulation in fetal and adult human fibroblasts.
AB  - Medium conditioned (CM) by human fetal fibroblasts stimulates proliferation in
      sparse cultures. This effect is inhibited by suramin and staurosporine,
      indicating the presence of autocrine growth factors in CM. On the contrary, CM
      inhibits DNA synthesis in confluent cultures, suggesting a regulatory role for
      the secreted factors. The growth regulatory profile of CM persists during in
      vitro ageing. However, it changes dramatically during the fetal-to-adult
      transition, as adult human fibroblasts are stimulated by CM, regardless of the
      culture density. These effects are similar to those that TGF-beta is known to
      have on fetal and adult human fibroblasts. Indeed TGF-beta is present in media
      conditioned by human fibroblasts, but CM-activity cannot be ascribed solely to
      this factor. Fibroblasts originating from different tissues exhibit the same
      autocrine regulatory features, suggesting the general character of this
      mechanism.

PMID- 9268715
TI  - Effect of a cytosolic Ca2+ concentration ramp on InsP3-induced Ca2+ release in
      A7r5 smooth-muscle cells and in EBTr cells from tracheal mucosa.
AB  - Inositol trisphosphate (InsP3) mediated Ca2+ release is modulated in a complex
      way by Ca2+. It is not known how the InsP3 receptor responds to a slowly
      increasing cytosolic [Ca2+]. Two different cell lines (A7r5 smooth-muscle cells
      and EBTr cells from tracheal mucosa) were investigated. We have now stimulated
      the Ca2+ stores of the permeabilized cells with a near-threshold [InsP3] and then
      increased the cytosolic [Ca2+] from 5 nM to 3 microM in 55 steps each lasting 6
      s. The rate of InsP3-induced Ca2+ release abruptly increased around 100 nM Ca2+
      and reached a maximum at 300 nM Ca2+, above which the Ca2+ release became
      smaller. The stimulatory effect of cytosolic Ca2+ was much less than that induced
      by elevating the [InsP3]. The time course of activation by Ca2+ in permeabilized
      cells resembles the fast InsP3-induced Ca2+ release following the pacemaker
      [Ca2+] rise in the agonist-stimulated intact cell.

PMID- 9268716
TI  - Induction of uncoupling protein-2 mRNA by troglitazone in the pancreatic islets
      of Zucker diabetic fatty rats.
AB  - Because troglitazone, like leptin, lowers the triglyceride (TG) content of
      pancreatic islets, we searched for other leptinomimetic actions. Leptin
      upregulates the expression of uncoupling protein-2 (UCP-2) mRNA in islets of
      normal rats, but has no effect in islets of obese Zucker Diabetic Fatty (ZDF)
      rats with mutated leptin receptors. We report here that troglitazone also
      increases the UCP-2/beta-actin mRNA ratio by 115% in wild type ZDF rats and by
      400% in obese ZDF rats.

PMID- 9268717
TI  - Modulation of lipid unsaturation and membrane fluid state in mammalian cells by
      stable transformation with the delta9-desaturase gene of Saccharomyces
      cerevisiae.
AB  - The composition and physical state of membrane lipids determine the dynamic
      nature of membranes, which in turn, could directly be linked to the activity of
      various membrane-associated cellular functions. To better understand the
      molecular basis of different membrane-related phenomena we established a novel
      strategy to alter unsaturation of mammalian cell membranes with an identical
      genetic background. We transfected L929 mouse fibroblastoid cells with DNA
      constructs containing the Delta9-fatty acid desaturase gene (Ole1) of S.
      cerevisiae under the control of desaturase promoters derived either from wild
      type or mutant strains of the dimorphic fungus H. capsulatum.

PMID- 9268718
TI  - Suppression of the protein tyrosine phosphatase LAR reduces apolipoprotein B
      secretion by McA-RH7777 rat hepatoma cells.
AB  - Apolipoprotein B (apo B) secretion is reduced by insulin in rat hepatocytes. To
      evaluate possible mechanisms by which insulin action leads to inhibition of apo B
      secretion, we evaluated the effect of suppression of the protein-tyrosine
      phosphatase LAR on apo B secretion by McA-RH7777 (McA) rat hepatoma cells. A
      reduction in cellular LAR levels was accomplished by stable transfection of McA
      cells with LAR antisense cDNA. Previous studies indicate that LAR-antisense
      transfectants demonstrate increased insulin receptor signaling. In current
      studies, reduced LAR expression results in a 60% to 70% reduction in apo B
      secretion compared with null vector control. The reduction in apo B secretion
      correlated with a significant decrease in cellular apo B mRNA levels. Results
      suggests there is a relationship of protein tyrosine phosphorylation with
      regulation of apo B mRNA abundance in McA cells.

PMID- 9268719
TI  - 17beta-estradiol inhibits apoptosis of endothelial cells.
AB  - Endothelial cells provide an antithrombotic and anti-inflammatory barrier for the
      normal vessel wall. Dysfunction of endothelial cells has been shown to promote
      atherosclerosis, and normalization of previously dysfunctional endothelial cells
      can inhibit the genesis of atheroma. In normal arteries, endothelial cells are
      remarkably quiescent. Acceleration of the turnover rate of endothelial cells can
      lead to their dysfunction. Apoptosis is a physiological process that contributes
      to vessel homeostasis, by eliminating damaged cells from the vessel wall.
      However, increased endothelial cell turnover mediated through accelerated
      apoptosis may alter the function of the endothelium and therefore, promote
      atherosclerosis. Apoptotic endothelial cells can be detected on the luminal
      surface of atherosclerotic coronary vessels, but not in normal vessels. This
      finding links endothelial cell apoptosis and the process of atherosclerosis,
      although a causative role for apoptosis in this process remains hypothetical.
      Estrogen metabolites have been shown to be among the most potent anti-atherogenic
      agents available to date for post-menopausal women. The mechanism of estrogen's
      protective effect is currently incompletely characterized. Here we show that
      17beta-estradiol, a key estrogen metabolite, inhibits apoptosis in cultured
      endothelial cells. Our data support the hypothesis that 17beta-estradiol's anti
      apoptotic effect may be mediated via improved endothelial cell interaction with
      the substratum, increased tyrosine phosphorylation of pp125 focal adhesion
      kinase, and a subsequent reduction in programmed cell death of endothelial cells.
      Inhibition of apoptosis by estrogens may account for some of the anti-atherogenic
      properties of these compounds.

PMID- 9268720
TI  - Intracellular distribution of stress glycoproteins in a heat-resistant cell model
      expressing human HSP70.
AB  - Heat stress results in the cellular accumulation of heat-shock proteins (HSP) and
      increased protein glycosylation. Among known stress glycoproteins, GP50 and GP62
      are associated with the expression of thermotolerance. In the present study, we
      characterized subcellular localization and redistribution of GP62 and GP50 in a
      rodent cell line, M21, before and after cellular heat-stress. M21 cells are heat
      resistant cells that overexpress human HSP70 and also have concomitantly high
      GP62 levels. Cellular fractionation by differential centrifugation showed that
      GP62 and GP50 was present in each subcellular fraction. However, each stress
      glycoprotein exhibited a characteristic kinetic pattern of redistribution during
      cellular recovery after heat stress. For example, glycosylated GP62 was seen
      predominantly in the mitochondria before heat-stress. Immediately after heat
      stress, its presence in the mitochondrial fraction was dramatically reduced,
      while it increased in lysosomes, microsomes and cytosol. By 1 h after heat
      stress, it had largely disappeared from microsomal and cytosolic fractions. After
      24 h, all subcellular fractions showed only trace amounts of residual GP62. By
      comparison, GP50 was also highest in the mitochondrial fraction before heat
      stress, redistributed like GP62 immediately after heat stress, but remained
      relatively unchanged thereafter. In contrast to GP62, GP50 showed little
      redistribution during 24 h after heat-stress and remained at high concentrations
      in all cell fractions, including microsomes. Distribution of GP50 and GP62 before
      and after heat stress, based on differential centrifugation, was consistent with
      immunolocalization data. Following heat stress, both GP50 and GP62 showed a
      partial overlap in distribution with HSP70. The above results indicate that each
      stress glycoprotein has a specific subcellular location, both before and after
      heat stress. The presence of GP62 in virtually all cell fractions is consistent
      with a multifunctional role for GP62 in the cellular stress response.

PMID- 9268721
TI  - Botulinum E toxin light chain does not cleave SNAP-23 and only partially impairs
      insulin stimulation of GLUT4 translocation in 3T3-L1 cells.
AB  - The stimulation of glucose uptake into fat and muscle by insulin results
      predominantly from the translocation of the glucose transporter, GLUT4, from an
      intracellular vesicle pool to the cell surface. Homologues of several key
      proteins known to be involved in the process of synaptic vesicle fusion have been
      identified on GLUT4 vesicles, including VAMP2 and cellubrevin. Syntaxin 4, SNAP
      23 and/or SNAP-25 are also implicated in this process. Bacterial toxins that
      specifically cleave these proteins have been utilised to assess their involvement
      in cell function. We aimed to distinguish which of the SNAP isoforms are
      specifically involved in GLUT4 translocation. Here we show that both human (h)
      and mouse (m) SNAP-23, unlike SNAP-25, are not substrates for Botulinum E toxin
      light chain (BoNT/E). Furthermore, we demonstrate that microinjection of
      differentiated 3T3-L1 cells with BoNT/E inhibited insulin stimulation of GLUT4
      translocation only slightly, 27%, whereas tetanus toxin light chain, that cleaves
      VAMP2, inhibited insulin stimulation of GLUT4 translocation by 80%. These studies
      therefore do not support a major role for SNAP-25 in insulin stimulation of GLUT4
      translocation and place SNAP-23 as a prime candidate for a role in this process.

PMID- 9268722
TI  - Chimeric D2/D3 dopamine receptor coupling to adenylyl cyclase.
AB  - We have sought to determine which area of the D2 dopamine receptor's third
      intracellular loop contributes to G-protein coupling by constructing reciprocal
      chimeric D2/D3 receptors with fusion points near the center of the third
      intracellular loop. Both receptor chimeras were expressed equally well in Chinese
      Hamster Ovary (CHO) cells and exhibited ligand binding properties similar to
      those of the wild type receptors. Surprisingly, both of the D2/D3 receptor
      chimeras were able to effectively inhibit adenylyl cyclase activity to almost the
      same extent as that seen with the D2 receptor whereas the D3 receptor was without
      effect. These results suggest that the D2 receptor possesses two redundant and
      independent domains for G-protein coupling and inhibition of adenylyl cyclase
      activity.

PMID- 9268723
TI  - Three different endogenous alpha-L-fucosyltransferases expressed in COS cells.
AB  - The monkey kidney COS cell line is frequently used for the transient expression
      of cloned human fucosyltransferase cDNAs in the belief that negligible endogenous
      expression of fucosyltransferase genes occurs in these cells. In the course of
      transfection experiments we observed weak cell surface expression of sialyl-Lex
      and weak fucosyltransferase activity in extracts of control untransfected cells.
      Since these activities could complicate interpretation of the results with the
      transfected genes, a more detailed examination was undertaken that has now
      revealed expression of three different fucosyltransferases in the cells. One
      enzyme, which utilises N-acetyllactosamine as substrate, has a pH optimum of 7.0,
      is resistant to heat inactivation, and has been tentatively identified as an
      alpha1,3-fucosyltransferase. A second enzyme which acts on asialo-fetuin has a pH
      optimum of 5.5 and is rapidly inactivated by heat; the acceptor sugar and
      positional linkage of the transferred fucose are not yet established. A third
      enzyme that utilises asialo-agalacto-fetuin as acceptor is provisionally
      identified as an alpha1,6-fucosyltransferase.

PMID- 9268724
TI  - Functional incorporation of P-glycoprotein into Xenopus oocyte plasma membrane
      fails to elicit a swelling-evoked conductance.
AB  - Microinjecton of Xenopus oocytes with P-glycoprotein-containing membranes from
      multidrug resistant cells following a recently published procedure resulted in
      the transplantation of the protein to the plasma membrane of the oocytes and was
      confirmed by Western blot analysis. These oocytes showed a reduced intracellular
      accumulation of daunomycin, when compared to uninjected oocytes or to those
      injected with membrane vesicles lacking P-glycoprotein, thus indicating that the
      protein had been incorporated in a transport-competent form. On the other hand,
      transplantation of P-glycoprotein to the oocyte membrane did not significantly
      change either the appearance or the properties of swelling-elicited membrane
      conductance with respect to those determined in oocytes either uninjected or
      injected with membranes lacking P-glycoprotein. These results do not support a
      role for P-glycoprotein as a swelling-activated chloride channel.

PMID- 9268725
TI  - Regulation of intracellular calcium release channel function by arachidonic acid
      and leukotriene B4.
AB  - Arachidonic acid has been shown to affect the intracellular calcium concentration
      in many cell types (1-5), but the target of this regulation was unclear. Here we
      show that two types of intracellular calcium release channel, the inositol 1,4,5
      trisphosphate-gated channel (IP3R) and the ryanodine receptor (RyR) are modulated
      in an opposing manner by arachidonic acid and its product leukotriene B4 (LTB4).
      The IP3R was inhibited by arachidonic acid (Ki = 27 nM), whereas the RyR was
      unaffected by this compound. In contrast, 100 nM LTB4 fully activated the RyR but
      did not influence the IP3R. The concerted action of arachidonic acid and LTB4
      could provide specific mobilization of stored calcium by terminating IP3-induced
      release and activating the RyR/calcium release channel by its newly identified
      agonist.

PMID- 9268726
TI  - Gene structure for mouse glutathione reductase, including a putative
      mitochondrial targeting signal.
AB  - Glutathione reductase (GR) is an important component of cellular antioxidant
      defense functions. Although GR activities are found in mitochondria and
      cytoplasm, the sorting mechanisms of mammalian GR into mitochondria have not been
      elucidated. To identify the mouse GR gene structure, including a sequence for a
      potential mitochondrial targeting signal (MTS), we screened a mouse genomic
      library and isolated four contiguous clones that covered the entire coding region
      of the gene. The coding region is composed of 13 exons. Exon 1 has two in-frame
      start codons separated by a sequence for an arginine-rich peptide segment.
      Expression studies, in which Chinese hamster ovary cells were transiently
      transfected with a plasmid containing the first 78 bp of the mouse exon 1
      attached 5' to the human GR cDNA, showed marked and selective increases in
      mitochondrial GR activities. The data indicate that this 78 bp sequence encodes a
      potential MTS for GR in mice.

PMID- 9268728
TI  - Accelerative sliding of myosin-coated glass-beads under suspended condition from
      actin paracrystal.
AB  - The maximum sliding velocity of rabbit skeletal-muscle myosin is about 10
      micron/sec under zero load and physiological conditions. We have found, however,
      that a large glass-bead (diameter, 65 micron) coated by rabbit skeletal myosin
      slides at 338 +/- 47 micron/sec under a condition suspended from an actin
      paracrystal surface. Also the sliding velocity increases exponentially as the
      size of myosin-coated glass-beads increases. We report here that the sliding
      velocity of myosin can be controlled by the adhesion force and the external
      normal force acting between actin and myosin.

PMID- 9268727
TI  - Inhibition of protein tyrosine kinase by 5-S-GAD, a novel antibacterial substance
      from an insect.
AB  - The effect of N-beta-alanyl-5-S-glutathionyl-dopa (5-S-GAD), a compound
      originally isolated from Sarcophaga peregrina (a flesh fly) as an antibacterial
      substance, on protein phosphorylation was examined using v-src-transformed NIH3T3
      cell lysates. 5-S-GAD was found to inhibit tyrosine phosphorylation of protein
      tyrosine kinase v-src, but not serine/threonine phosphorylation of protein kinase
      C. The potency of this compound was comparable to that of herbimycin A. Our
      results suggested that a substitution at position 5 of the catechol in 5-S-GAD
      with the sulfur of cysteine is essential for 5-S-GAD to inhibit protein tyrosine
      kinase v-src.

PMID- 9268729
TI  - Evolution of a mitochondrial tRNA PHE gene in A. thaliana: import of cytosolic
      tRNA PHE into mitochondria.
AB  - Previously we have described a putative tRNATyr in Arabidopsis thaliana
      mitochondria, the sequence of which is different from that of other plant
      mitochondrial tRNATyr genes. We show here that this tRNATyr gene sequence is
      present in several copies in the mitochondrial genome of A. thaliana. One copy of
      these tRNATyr gene sequences, termed here tRNATyr-1, could encode a functional
      tRNA. Expression analysis has shown that the tRNATyr-1 gene is cotranscribed with
      the downstream tRNAGlu gene, and that the corresponding mature-sized tRNA is
      present in mitochondria. We also show that the native tRNATyr gene, similar to
      the mitochondrial tRNATyr genes found in plants, is present in the A. thaliana
      mitochondrial genome and expressed. The tRNATyr-1 gene has been previously
      suggested to be derived from a tRNAPhe gene sequence. We show here that, as a
      consequence, there is no tRNAPhe gene in the mitochondrial genome of A. thaliana
      and that a cytosolic tRNAPhe is imported in A. thaliana mitochondria.

PMID- 9268730
TI  - Differential inhibition of telomerase activity during induction of
      differentiation in hematopoietic, melanoma, and glioma cells in culture.
AB  - Accumulating evidence indicates that telomerase activity is stringently repressed
      in normal human somatic cells but reactivated in cancers and immortal cells,
      suggesting that activation of telomerase activity may play a role in
      carcinogenesis and immortalization. Recently, down-regulation of telomerase
      activity by induction of differentiation has been reported for cells of pre
      myelocytic and myelocytic leukemia as well as embryonic carcinoma. To gain
      further insight about the regulation of telomerase activity following induction
      of differentiation, telomerase activity was examined in a human hematopoietic
      progenitor cell line (D2), a melanoma cell line (CM73-36) and a glioma cell line
      (Ast812) before and after addition of differentiation inducing agents. The state
      of differentiation was assessed by growth inhibition and cell morphological
      maturation. Telomerase activity was assayed by a PCR-based telomeric repeat
      amplification protocol (TRAP). Our data show that telomerase activity was
      inhibited only in differentiation-induced D2 cells but not in differentiation
      induced melanoma and glioma cells. A model for the differential inhibition of
      telomerase activity following induction of differentiation in different cancer
      cells will be presented.

PMID- 9268731
TI  - Synthesis of dehydroluciferin by firefly luciferase: effect of dehydroluciferin,
      coenzyme A and nucleoside triphosphates on the luminescent reaction.
AB  - The formation of dehydroluciferin (L) from luciferin (LH2) in the reaction
      catalyzed by firefly luciferase (EC 1.13.12.7) has been studied. The E.LH2-AMP
      complex may follow two different pathways: towards production of light and
      towards the synthesis of the E.L-AMP complex. This last step has an inhibitory
      effect on light emission as molecules of the enzyme are trapped in a light
      unproductive complex. The effects of CoA and nucleoside 5'-triphosphates (NTPs)
      on light emission are quantitatively different. CoA combines with the L moiety of
      the E.L-AMP complex, yielding L-CoA, promoting liberation of free luciferase, and
      increasing light yield. NTP reacts with the AMP moiety of the same complex,
      generating adenosine(5')tetraphospho(5')nucleoside (Ap4N) and, probably, the E. L
      complex and scarcely increasing light production. The results are discussed in
      relation to previous reports, by others, on luciferase.

PMID- 9268732
TI  - A protein with a novel calcium-binding domain associated with calcareous
      corpuscles in Echinococcus granulosus.
AB  - A novel intracellular calcium-binding protein from Echinococcus granulosus is
      described in this work. A cDNA was isolated from a lambdagt11 protoscolex
      expression library and the deduced amino acid sequence has at least fifteen
      sequentially repeated twelve-residue repeats that resemble the calcium-binding
      loop of EF-hands; however, the dodecamer motif has no flanking helices. The cDNA
      was expressed in Escherichia coli using the pGEX vector, and a recombinant fusion
      protein (EgCaBP1-GST) was obtained. The recombinant fusion protein binds calcium
      when assayed with 45Ca. It is possible that the calcium-binding motifs present a
      secondary structure similar to the parallel beta roll structure described for an
      alkaline protease from Pseudomonas aeruginosa. A native protein of more than 300
      kDa was recognized by an anti-EgCaBP1 monoclonal antibody by Western-blot
      analysis. Immunohistochemistry using a pool of anti-EgCaBP1-GST mouse sera
      demonstrated a strong association of the protein with calcareous corpuscles. The
      possible role of this protein and that of the calcareous corpuscles in the
      protoscolex are discussed.

PMID- 9268733
TI  - Sodium butyrate induces NIH3T3 cells to senescence-like state and enhances
      promoter activity of p21WAF/CIP1 in p53-independent manner.
AB  - Sodium butyrate, a histone deacetylase inhibitor, has been shown to induce
      differentiation of many cancer cells and senescence-like state of human
      fibroblasts. Here we show that sodium butyrate also induces senescence-like state
      of NIH3T3 cells. The treated cells were blocked at G1 phase and featured
      morphologically like senescent cells with enlarged cytoplasm and multiple nuclei.
      The expression of p21(WAF/CIP1) (p21) increased after sodium butyrate treatment
      at transcriptional level. To analyze the induction of promoter activity, we
      isolated 4.6 kb of murine p21 promoter and inserted it upstream of a luciferase
      reporter gene. When this construct was transiently transfected into NIH3T3 cells,
      sodium butyrate enhanced the luciferase activity. p53 independency of sodium
      butyrate-inducible p21 promoter activity was confirmed by using the deletion
      mutants lacking p53 binding sites and p53 deficient cells in transfection
      experiments.

PMID- 9268734
TI  - Human immunodeficiency virus type 1 TAT protein activates B lymphocytes.
AB  - HIV-1 infection causes B cell hyperactivation. Tat protein, a potent virus
      encoded transactivator, has the potential to activate B cells based on its
      pleiotropic biological properties: (1) Tat regulates cellular gene expression;
      (2) Tat modulates growth of various cell types; and (3) Tat is released from
      infected T cells and acts on bystander uninfected cells in a paracrine fashion.
      To test a possible activating effect of Tat on B cells, we examined the effect of
      purified Tat on the expression of Fas, an activation marker, in B cells in
      primary culture. Flow cytometric analysis demonstrated that treatment of
      peripheral blood mononuclear cells with Tat, at concentrations in the range of
      extracellular Tat as determined in vivo, up-regulated Fas expression in B cells.
      Reverse transcriptase-PCR further demonstrated that Tat induced Fas expression in
      B cells at the mRNA level. These results indicate that exogenous Tat alone can
      activate B cells, suggesting that Tat may contribute to B cell hyperactivation
      during the early stage of HIV-1 infection and activation-induced B cell death
      mediated by Fas during the late stage of HIV-1 infection.

PMID- 9268736
TI  - Developmental profile of homeobox gene expression during 3T3-L1 adipogenesis.
AB  - The homeobox family of proteins are transcription factors are known to be
      important during the differentiation of a variety of mammalian tissues, however,
      expression of the genes encoding homeobox proteins during adipogenesis or in
      adipose tissue has not been described. To investigate whether members of the
      homeobox gene family are expressed and regulated during adipocyte
      differentiation, RNA was isolated from 3T3-L1 preadipocyte cells during the
      hormonal induced differentiation of this cell line into adipocytes. A reverse
      transcriptase-polymerase chain reaction strategy using degenerate oligonucleotide
      primers complementary to the highly conserved homeodomain resulted in the
      identification of 10 different homeobox genes expressed during 3T3-L1
      adipogenesis. One of the clones appears to be unique and 9 of the clones
      represented known members of the homeobox gene family. Examination of the
      relative mRNA levels encoding these proteins by ribonuclease protection assay
      during adipocyte differentiation revealed that 3 members, Hox a4, Hox a7, and Hox
      d4, are regulated as a function of adipocyte development. Further examination of
      RNA isolated from murine retroperitoneal adipose tissue revealed that these three
      regulated homeobox mRNAs are expressed in vivo. Combined, these results suggest
      that members of the homeobox gene family may serve an important role during the
      differentiation of adipocytes.

PMID- 9268735
TI  - Induction of osteogenic differentiation by hedgehog proteins.
AB  - In this study we asked whether members of the hedgehog gene family are involved
      in osteogenesis. C3H10T1/2 cells and MC3T3-E1 cells expressed the putative
      hedgehog receptor patched (Ptc) gene. Medium conditioned by chicken embryo
      fibroblast cultures expressing either Indian hedgehog or Sonic hedgehog
      stimulated alkaline phosphatase (APase) activity in cultures of the mouse
      mesenchymal cell line C3H10T1/2 and the osteoblastic cell line MC3T3-E1. These
      stimulatory effects were synergistically enhanced by bone morphogenetic protein-2
      (BMP-2). Treatment with the amino-terminal portion of recombinant Sonic hedgehog
      proteins (rShh-N) up-regulated the expression of the Ptc gene within 12 h and
      increased production of APase in C3H10T1/2. rShh-N and BMP-2 also synergistically
      stimulated APase activity. rShh-N treatment did not affect the expression levels
      of Bmp-2, -4, -5, -6 and -7 genes. These findings indicate that hedgehog proteins
      directly act on osteogenic precursor cells and osteoblasts and stimulate
      osteogenic differentiation of these cells in co-operation with BMPs.

PMID- 9268737
TI  - Increase in serum leptin and uterine leptin receptor messenger RNA levels during
      pregnancy in rats.
AB  - Pregnancy is a physiological state associated with significant changes in
      appetite, thermogenesis, and lipid metabolism, functions which are regulated in
      part by a hormone, leptin, secreted by adipocytes. Leptin has also been shown to
      have a role in reproduction, promoting centrally-regulated maturation of the
      reproductive system and signaling the presence of adequate maternal energy stores
      for fertility. Here we demonstrate that serum leptin levels are modulated during
      normal rat pregnancy with a 1.8-fold increase during pregnancy followed by a
      decrease just before parturition. Leptin receptor mRNA levels in the uterus are
      also regulated with an increase about 2.7-fold during this same period, whereas
      there is no change in other tissues examined. The results suggest that leptin may
      play a role during pregnancy, perhaps regulating energy utilization.

PMID- 9268738
TI  - Silica.

PMID- 9268739
TI  - Some silicates.

PMID- 9268740
TI  - Coal dust.

PMID- 9268741
TI  - para-Aramid fibrils.

PMID- 9268742
TI  - Indications, contraindications and possible side-effects of climatotherapy at the
      Dead-Sea.

PMID- 9268743
TI  - Multidrug therapeutic challenges in leprosy.

PMID- 9268744
TI  - Malignant melanoma: a review of 75 malpractice cases.

PMID- 9268745
TI  - Melanoma on dysplastic nevus spilus.
AB  - BACKGROUND: Nevus spilus is found with relative frequency. It is observed as as
      tan to brown macule serving as base to a speckle of smaller and darker maculo
      papular elements. On rare occasions it turns into a malignant melanoma. PURPOSES:
      To describe one case with some characteristics different from routine
      observations and to revise the cases published reporting nevus spilus that turned
      into malignant melanoma, in order to point out the most frequent aspects.
      RESULTS: The 17 patients with nevus spilus and melanomas, including ours, were
      white, with ages between 35 and 56 years. Most of the cases were localized in the
      dorsal region. Five patients were men. Almost all nevus were congenital and their
      size ranged between 2 and 10 cm in diameter. Histologically, the speckled spots
      were junctional nevus, and few of them had dysplastic characteristics. Melanomas
      corresponded to the extensive superficial type MES; one of them was nodular. Some
      had systemic ganglial metastases and three of the patients are known to have
      died. Our patient had an intradermal cellular nevus on the man spot, and terminal
      hairs could be observed on it. The speckled elements were junctional nevus with
      dysplastic cells. CONCLUSIONS: Nevus spilus must be closely monitored, because it
      may turn into a malignant melanoma.

PMID- 9268746
TI  - Basal cell carcinomas of covered and unusual sites of the body.
AB  - BACKGROUND: The concept of unusual site for a basal cell carcinoma (BCC) has to
      be defined because there is much confusion about it. Basal cell carcinomas of
      covered areas of the body are sometimes considered as unusual because of their
      location. In this study an attempt is made to define what is an unusual site for
      a BCC according to experience and the problems encountered are briefly discussed.
      METHODS: A total of 1050 histologically-confirmed primary BCCs were studied. Age,
      sex and site of presentation were considered. RESULTS: Eighteen cases were
      recorded, localized on hand, axilla, areola or nipple, buttock perineal, and
      genital regions. CONCLUSIONS: Unusual location has been arbitrarily defined in
      the past according to the incidental percentage, to a mathematical index of
      density, to the literature reports. All these criteria suffer more or less from
      some discrepancy, but in our opinion all these should be considered for a
      definition. Our results, moreover, suggest that only the above described sites
      should be considered.

PMID- 9268747
TI  - Striae distensae of pregnancy. An in vivo biomechanical evaluation.
AB  - BACKGROUND AND OBJECTIVE: Striae distensae of pregnancy is a common finding.
      There is currently a lack of information about the rheological characteristics of
      such lesions. The purpose of this study was to compare the mechanical properties
      of striae distensae before and after delivery. PATIENTS AND METHODS: A total of
      79 primigravid entered the study. Rheological properties of skin were evaluated
      in vivo using a Cutometer equipped with a 2-mm probe. RESULTS: Mechanical
      properties of striae distensae developing during pregnancy resembled those of the
      surrounding skin. By contrast, significant differences were yielded during post
      partum. Extensibility of striae distensae was increased although parameters of
      elasticity remained normal. CONCLUSIONS: Rheological properties of striae
      distensae of pregnancy vary in time. This might reflect the changes in hormones
      and in the mechanical stresses normally setting the skin under tension.

PMID- 9268748
TI  - Impaired neutrophil functions in patients with leukocytoclastic vasculitis.
AB  - BACKGROUND: Leukocytoclastic vasculitis (LV) is characterized by segmental
      inflammation of small blood vessels, resulting in ischemic damage to the
      surrounding tissue. It is considered to be related to a type III hypersensitivity
      reaction, although the exact etiologic mechanism is not clear. OBJECTIVE: The
      purpose of this study was to evaluate neutrophil functions in patients with LV in
      order to understand their role in the pathogenesis of the disease. METHODS:
      Neutrophil functions were examined in 25 LV patients. The patients were divided
      into two groups: Group A consisted of 14 patients with drug-induced LV and Group
      B consisted of 11 patients where LV was induced by other factors. RESULTS: Both
      groups of patients showed significantly reduced chemotaxis and phagocytosis.
      Superoxide generation was significantly lower (P < 0.001) only in neutrophils
      from patients in Group A: 5.8 +/- 0.5 nmoles O2/10(6) cells/min compared to 9.08
      +/- 0.8 nmoles O2/10(6) cells/min in the controls. Preincubation on normal
      neutrophils with the patients' sera caused an increase in their superoxide
      generation in accordance with the high IL-8 levels in these sera. CONCLUSIONS:
      Neutrophil functions were significantly impaired in patients with LV. It is
      likely that factors present in LV plasma may chronically activate neutrophils, so
      that they become refractory to further stimulation. Our study showed that
      neutrophil superoxide generation is low only in drug-induced LV; this test may
      assist in distinguishing such patients from those with LV induced by other
      causes.

PMID- 9268749
TI  - Lymphomatoid papulosis type A: clinical, morphologic, and immunophenotypic study.
AB  - BACKGROUND: Lymphomatoid papulosis (LyP) is a cutaneous clonal or polyclonal Ki-1
      + T-cell lymphoproliferative disorder, morphologically resembling Ki-1 +
      anaplastic large cell lymphomas (Ki-1 + ALCL) or Hodgkin's disease (HD).
      Lymphomatoid papulosis usually has a characteristic benign clinical course with
      remissions and relapses of the cutaneous eruptions. METHODS: The authors studied
      three patients with LyP. In each case the diagnosis was established based on the
      typical clinical history and presentation of the cutaneous lesions as well as the
      morphologic and immunophenotypic findings. RESULTS: In all three cases the skin
      biopsies showed a polymorphic, nonepidermotropic, dermal lymphocytic infiltrate,
      composed of small lymphocytes and fewer large, atypical cells. The large cells
      were positive for the activation markers CD30 (Ki-1) and CD45R (leukocyte common
      antigen), and were negative for the HD marker CD15 (Leu MI). CONCLUSIONS: In most
      cases, LyP can be distinguished from Ki-1 + ALCL and HD on the basis of clinical,
      morphologic, and/or immunophenotypic findings. We emphasize the importance of the
      recognition of LyP as a clinicopathologic entity and the awareness of
      dermatologists, oncologists, and surgical pathologists in differentiating LyP
      from other primary cutaneous Ki-1 + lymphoproliferative disorders (Ki-1 + ALCL
      and HD). The prognosis of cutaneous Ki-1 + ALCL and HD is usually different from
      LyP and requires a different therapeutic approach.

PMID- 9268750
TI  - Annular atrophic plaques of the skin (Christianson's disease).

PMID- 9268751
TI  - Congenital hemangiopericytoma of the skin.

PMID- 9268752
TI  - Wells' syndrome related to tetanus vaccine.

PMID- 9268754
TI  - Hereditary bullous acrokeratotic poikiloderma of Weary-Kindler associated with
      pseudoainhum and sclerotic bands.

PMID- 9268753
TI  - Retroperitoneal round-cell liposarcoma associated with paraneoplastic pemphigus
      presenting as lichen planus pemphigoides-like eruption.

PMID- 9268755
TI  - Vitiligo following the resolution of psoriatic plaques during PUVA therapy.

PMID- 9268756
TI  - Calcipotriol in psoriasis vulgaris: a controlled trial comparing betamethasone
      dipropionate + salicylic acid.

PMID- 9268757
TI  - Treatment of tinea capitis with itraconazole.

PMID- 9268758
TI  - Treatment of chromoblastomycosis with itraconazole, cryosurgery, and a
      combination of both.
AB  - BACKGROUND: Chromoblastomycosis is a subcutaneous mycosis, seen frequently in
      tropical areas, and caused by dematiaceous fungi. It produces nodulo-verrucous
      lesions in the arms and legs. There is no treatment of choice for this disease
      and sometimes a combination of chemotherapy and physical therapy is necessary.
      METHODS: The study included 12 patients diagnosed with chromoblastomycosis by
      means of fungal and histopathologic tests. The patients were assigned to three
      treatment groups: patients with small lesions, not greater than 15 cm2 in area,
      were assigned to Group 1, in which the treatment consisted of itraconazole 300
      mg/day, or to Group 2, in which the treatment consisted of one or more sessions
      of open-spray cryosurgery. Patients with large lesions were assigned to Group 3
      and started treatment with itraconazole 300 mg/day, until a maximal reduction of
      lesions occurred, and then underwent one or several cryosurgery sessions.
      Clinical, fungal, and laboratory tests were performed in each group before,
      during, and at the completion of treatment. RESULTS: Positive cultures of
      Fonsecaea pedrosoi were obtained in 11 out of 12 patients. Two out of four
      patients in Groups 1 and 3 had a clinical and fungal cure and the remaining
      patients experienced significant improvement. All four patients included in Group
      2 achieved a cure. No important side-effects were seen among the patients
      included in any of the two itraconazole groups, and only two out of eight
      patients reported gastric discomfort. The cryosurgery group reported only normal
      complications of the process, such as edema and pain; two out of eight patients
      had a superimposed infection. CONCLUSIONS: The results of itraconazole and
      cryosurgery were good in cases with small lesions; antifungal therapy being more
      appropriate for flexion areas. The combination of itraconazole, to reduce the
      size of the lesions, with subsequent treatment of the remaining lesions with
      cryosurgery, represents a new alternative in the treatment of patients with large
      lesions. Both types of therapy are considered safe, with few side-effects.

PMID- 9268759
TI  - Granuloma faciale: successful treatment of nine cases with a combination of
      cryotherapy and intralesional corticosteroid injection.
AB  - BACKGROUND: Granuloma faciale is a rare disorder characterized by asymptomatic
      papules, nodules, and plaques on the face. Although the exact pathogenesis of
      this disease in unclear, it is considered a variant of leukocytoclastic
      vasculitis confined to the skin. Several medical and surgical methods have been
      used to treat it with variable results. CASE REPORTS: We report nine cases of
      granuloma faciale treated with a combination of cryotherapy with liquid nitrogen
      and intralesional injection of corticosteroids. RESULTS: The lesions cleared
      completely in all of the patients without any side-effects. No recurrences have
      been observed. CONCLUSIONS: Cryotherapy with liquid nitrogen, followed by
      intralesional injection of corticosteroids, is a safe and effective method to
      treat granuloma faciale.

PMID- 9268760
TI  - Sir Archibald Gray KCVO, CBE, MD, FRCP, FRCS, LLD, dermatologist, University
      College Hospital London, in his contributions to British and international
      dermatology.

PMID- 9268761
TI  - Budd-Chiari syndrome as a presenting syndrome for Behcet's disease.

PMID- 9268762
TI  - Behcet's disease and neutropenia.

PMID- 9268763
TI  - Generalized pustular dermatosis following paclitaxel therapy.

PMID- 9268764
TI  - Host-controlled cell-to-cell movement of a hybrid barley stripe mosaic virus
      expressing a dianthovirus movement protein.
AB  - The triple gene block (TGB) of barley stripe mosaic virus (BSMV), coding for
      viral movement proteins (MPs), was replaced by the single MP gene of red clover
      necrotic mosaic virus (RCNMV). Accumulation of the hybrid virus in barley plants
      (the selective host for BSMV) was reduced compared to BSMV. The hybrid virus
      induced small necrotic local lesions on Chenopodium amaranticolor leaves and did
      not infect Nicotiana clevelandii (the selective host for RCNMV). The hybrid virus
      accumulated in the inoculated leaves of Nicotiana benthamiana, but not in the
      upper noninoculated leaves. Thus the RCNMV MP gene substituted for the BSMV TGB
      in cell-to-cell movement, but not in systemic spread. Hybrid virus movement was
      efficient only in N. benthamiana, the common host for BSMV and RCNMV. These data
      point to the involvement of host-specific factors in the function of virus-coded
      transport determinants.

PMID- 9268765
TI  - Effects of protein tyrosine kinase inhibitors on the replication of herpes
      simplex virus and the phosphorylation of viral proteins.
AB  - The effect of protein tyrosine kinase (PTK) inhibitors on the replication of
      herpes simplex virus (HSV) was examined. Tyrphostins AG17, AG213, AG490, and
      AG555, and herbimycin A all inhibited the plaque formation of HSV type 1 (HSV-1)
      in Vero cells, but AG17, AG490, and AG555 exhibited a more selective antiviral
      effect. In the presence of 0.4 microM AG17, the virus production 24 h after
      infection was decreased to 7.7% of the untreated control level. Even if the
      treatment was started 12 h after the initiation of infection, the viral titer was
      reduced by 82.4%, compared with the untreated control level. In HSV-1-infected
      cells ICPs 6, 17/18, 19/20, and 25 were tyrosine-phosphorylated proteins. The
      synthesis and phosphorylation of these proteins were inhibited by AG17, and
      suppression of ICP 19/20, which were identified as the UL47 gene products, was
      the greatest. In contrast, the in vitro autophosphorylation of viral proteins was
      not affected by this PTK inhibitor. These results indicate that tyrphostin may
      represent a novel class of inhibitors of HSV-1, and that the viral proteins which
      have phosphorylated tyrosine residues and are suppressed by AG17 most
      significantly are the products of the UL47 gene, the tegument proteins VP13/14.

PMID- 9268766
TI  - Antiviral efficacies of famciclovir, valaciclovir, and brivudin in disseminated
      herpes simplex virus type 1 infection in mice.
AB  - The animal model of necrotic hepatitis caused by HSV-1 infection in juvenile mice
      was used to compare the efficacies of the oral antiherpes agents famciclovir
      (FCV), valaciclovir (VACV) and brivudin (BVDU). The experimental infection allows
      the measurement of viral replication in the liver by macroscopic lesions and the
      evaluation of mortality from encephalitis. Mice intravenously inoculated with a
      highly virulent clinical HSV-1 isolate were orally treated by gavage over a
      period of 3 days starting on day 2 post infection. The reference drug acyclovir
      (ACV) was administered subcutaneously. Necrotic hepatitis was significantly (p <
      0.01) reduced by treatment with FCV, VACV and ACV at a dose of 50 mg/kg per day
      divided into 3 doses. No significant effect was achieved with BVDU at 200 mg/kg
      per day. Treatment with FCV at 50 mg/kg per day, ACV at 100 mg/kg per day, and
      VACV at 200 mg/kg per day significantly (p < 0.001) decreased mortality in mice.
      BVDU treatment at 200 mg/kg per day did not reduce mortality but significantly
      prolonged (p < 0.05) the survival time.

PMID- 9268768
TI  - Protection of mice by an attenuated variant against the wild-type lymphocytic
      choriomeningitis virus.
AB  - L cells persistently infected with strain Armstrong lymphocytic choriomeningitis
      virus generated a variant which failed to develop the lethal neurologic disease
      after application to the brain. This virus was able to protect mice from the
      fatal consequences when inoculated intracerebrally prior to challenge with wild
      type (wt) virus. After infection of mice with the attenuated variant and
      thereafter with the wt virus, production of the latter was extraordinarily
      reduced. As expected, virus elimination was finally achieved by cytotoxic T
      lymphocytes, whose activation was accelerated. Furthermore, two events seem to
      play an important part in this enhanced virus reduction. First, from the
      beginning of the infection with wt virus, neutralizing antibodies could be
      noticed. The second observation was an excessive production of interferon-alpha 1
      day after the challenge infection.

PMID- 9268767
TI  - Identification of envelope glycoproteins H and B homologues of human herpesvirus
      7.
AB  - The genes encoding the envelope glycoprotein H (gH) and gB homologues were
      identified by sequencing genomic clones of human herpesvirus-7 (HHV-7), strain
      JI. A gB cDNA clone from HHV-7 strain AL was also identified. The deduced primary
      translation products of the gH and gB genes are a protein of 690 amino acids,
      with a predicted mass of 80.4 kD, and a protein of 822 amino acids, with a
      predicted mass of 93.3 kD, respectively. Both the predicted proteins have the
      characteristics of transmembrane glycoproteins, containing signal and
      transmembrane sequence motifs and characterized by the presence of 10 (gH) and 11
      (gB) potential motifs for N-glycosylation. Comparison of amino acid sequence of
      HHV-7 gH and gB with the homologous sequences of the other human herpesviruses
      reveals closest homology with HHV-6 (38.8% identity for gH, 56.2% identity for
      the gB). In addition, significant sequence similarity was also observed between
      the gH and gB of HHV-7 and the homologs encoded by human cytomegalovirus (21.6%
      identity for gH, 37.6% identity for gB). No significant differences existed
      between the gB sequence of the two different HHV-7 strains analyzed. The products
      of the HHV-7 gH and gB expressed transiently in eukaryotic cells were
      specifically recognized by an HHV-7-reactive human serum in immunofluorescence
      assays.

PMID- 9268769
TI  - Epitope mapping and functional characterization of monoclonal antibodies specific
      for herpes simplex virus type I DNA polymerase.
AB  - Three monoclonal antibodies (MAbs 1051a, 1051b and 1051c) were raised against a
      surface region (residues 597-686) of the herpes simplex virus type 1 (HSV-1) DNA
      polymerase (HSV pol), and their epitopes were mapped. The MAbs reacted serotype
      specifically with the native and denatured HSV pol, as shown by Western blot
      analysis, immunoprecipitation and immunofluorescence microscopy, indicating their
      usefulness for biochemical studies and clinical diagnosis of HSV-1 infections,
      MAb 1051c, displaying the least cross-reactivity with cellular proteins in the
      Western blot analysis, was successfully utilized not only for
      coimmunoprecipitation, but also for the analysis and three-dimensional modeling
      of the cellular sites of HSV pol interaction by confocal laser immunofluorescence
      microscopy.

PMID- 9268770
TI  - Regulation of infected-cell-specific protein synthesis in SF IPLB-21 cells
      productively infected with Spodoptera frugiperda multicapsid nuclear polyhedrosis
      virus.
AB  - In Spodoptera frugiperda (SF IPLB-21) cells productively infected with S.
      frugiperda multicapsid nuclear polyhedrosis virus (SfMNPV), we observed the
      synthesis of infected-cell-specific polypeptides (ICSPs) using the protein
      synthesis inhibitor cycloheximide (CX) and the DAN synthesis inhibitor cytosine
      arabinoside (Ara-C) in an attempt to assess whether a temporal cascade and viral
      DNA synthesis are involved in the gene expression program of SfMNPV. Inhibition
      of protein synthesis with CX at 0 h postinfection resulted in the active
      synthesis of a group of ICSPs immediately after removal of CX, suggesting that
      these polypeptides, designated alpha-ICSP, did not require de novo protein
      synthesis for their production. A second group of ICSPs (designated beta-ICSPs),
      requiring a prior interval of protein synthesis, was detected when CX was added
      at later times. A third group of ICSPs also needed an interval of ICSP synthesis,
      but differed from beta-ICSPs in that they required a longer interval of protein
      synthesis. Moreover, the synthesis of most of these ICSPs also required DNA
      synthesis, which was demonstrated by addition of Ara-C before and after viral DNA
      replication; these ICSPs were therefore designated gamma-ICSPs. In conclusion,
      two kinds of regulatory processes are involved in SfMNPV infection: the first
      process controls the sequential synthesis of the tree ICSP groups, that is alpha-
      >beta-->gamma; a second process represses the synthesis of ICSP groups, first of
      the alpha-ICSPs and subsequently of beta-ICSPs. Thus, we propose temporally
      regulated as well as negative control circuits in SfMNPV gene expression.

PMID- 9268771
TI  - The role and clinical significance of subsyndromal depressive symptoms (SSD) in
      unipolar major depressive disorder.
AB  - Analyses conducted in 10,526 community respondents investigated by the NIMH
      Epidemiological Catchment Area (ECA) Program, revealed the 1-month point
      prevalence of depressive symptoms and disorders in the general population, at the
      first ECA interview (Wave 1) to be 10%, as follows: 2.3% major depressive
      disorder (MDD); 2.3% dysthmic disorder (DD); 1.5% minor depressive disorder
      (MinD); and 3.9% subsyndromal depressive symptoms (SSD, defined as two or more
      depressive symptoms beneath the diagnostic threshold of MinD, DD or MDD). There
      appears to be two classes of SSD in this community sample: first, SSD, which
      occurred as an integral component of the course of unipolar major depressive
      disorder (MDD); and, second, SSD occurring spontaneously in non-unipolar
      depressed community subjects. In the first instance, SSD was frequently prodromal
      to episodes of MinD or MDD or residual to resolving episodes. Analyses also
      support the conclusion that SSD is a clinically significant, interepisode,
      depressive subtype of unipolar MDD, since SDD is associated with harmful
      dysfunction in five of six measures of adverse outcome, has a significantly
      increased prevalence of past histories of major depressive episodes, and an
      elevated lifetime prevalence of suicide attempts. Comparison of subsyndromal
      depressive symptomatology or depressive disorder diagnoses at Wave 1 with
      diagnoses obtained, 1 year later, at the Wave 2 interview, confirm the persistent
      and chronic nature of depression in this large representative sample of community
      respondents, in which 71% of subjects with depressive symptoms or disorders at
      Wave 1 continued to be symptomatic at Wave 2. In addition, subjects experienced a
      surprising degree of change in depressive symptom and disorder diagnoses during
      the 1-year observational window between Wave 1 and Wave 2, in which a remarkable
      percentage of individuals, who began the year in a depressive symptom or disorder
      diagnostic category, ended the year in another. This has led us to hypothesize
      that the typical clinical picture of unipolar MDD is dynamic and pleomorphic in
      nature, characterized by substantial symptomatic fluidity, in which patients
      frequently change diagnoses from one depressive subtype to another during their
      courses of illness.

PMID- 9268772
TI  - Prevalence, correlates, and course of minor depression and major depression in
      the National Comorbidity Survey.
AB  - Data from the National Comorbidity Survey are used to study the lifetime
      prevalences, correlates, course and impairments associated with minor depression
      (mD), major depression 5-6 symptoms (MD 5-6), and major depression with seven or
      more symptoms (MD 7-9) in an effort to determine whether mD is on a continuum
      with MD. There is a monotonic increase in average number of episodes, average
      length of longest episode, impairment, comorbidity, and parental history of
      psychiatric disorders as we go from mD to Md 5-6 to MD 7-9. In most of these
      cases, though, the differences between mD and MD 5-6 are no longer than the
      differences between MD 5-6 and MD 7-9, arguing for continuity between mD and MD.
      Coupled with the finding from earlier studies that subclinical depression is a
      significant risk factor for major depression, these results argue that minor
      depression is a variant of depressive disorder that should be considered
      seriously both as a target for preventive intervention and for treatment. The
      paper closes with suggestions regarding the analysis of mD subtypes in future
      longitudinal studies.

PMID- 9268773
TI  - The depressive spectrum: diagnostic classification and course.
AB  - The spectrum of depression is much wider than that reflected in the current
      diagnostic nomenclature. A large proportion of subjects with depression both in
      treatment and in the community fail to meet diagnostic criteria for either major
      depressive disorder (MDD) or dysthymia. Inclusion of subthreshold categories of
      depression dramatically improves the coverage of treated depression, particularly
      in community samples, and better enables the characterization of its longitudinal
      course. This paper investigates the application of diagnostic criteria for both
      threshold and subthreshold categories of depression in a prospective longitudinal
      community study of young adults from Zurich, Switzerland. We present the
      prevalence and treatment rates of each of the depressive subtypes, the degree of
      diagnostic overlap and the longitudinal stability of subthreshold and threshold
      categories of depression. The findings indicate that the prevalence rates of
      subthreshold categories of depression are quite high in the community, and that a
      substantial proportion of subthreshold depressives, particularly those with
      recurrent depression, receive treatment. There is a strong tendency for
      individuals to meet multiple depressive subtypes over time, with little stability
      of individual categories among those who continue to manifest depression over a
      15-year period. The prospective longitudinal data reveal that major depression is
      both an antecedent to and sequela of subthreshold categories, providing evidence
      for the validity of the spectrum concept of depression. However, the need for a
      threshold for the symptom criteria is suggested by the lack of predictive value
      of minor depression and depressive symptoms only. These result suggest that both
      the current symptom threshold for a depressive syndrome and recurrence, but not
      the minimum duration of depressive episodes, are important components of the
      classification of depression.

PMID- 9268774
TI  - The relationship between major and subthreshold variants of unipolar depression.
AB  - Recent epidemiological research in the general population and primary care
      demonstrated that a substantial proportion of disabling depressive syndromes do
      not meet the diagnostic criteria for major depression. This observation proposes
      less restrictive diagnostic definitions of depression. However, a gain in
      sensitivity may induce a substantial loss of specificity. A variety of diagnostic
      definitions of subthreshold depression has been proposed balancing both aspects.
      However, the less restrictive diagnostic definitions are, the lower the
      specificity. This report explores variants of subthreshold depression
      characterized by current and subsequent disability in a prospectively
      investigated sample of general practice patients (n = 400), recruited within the
      framework of the WHO study "Psychological Problems in Primary Care and a survey
      in the general population. Duration of episodes, recurrence and number of
      associated symptoms are the main diagnostic variables. Brief depression with
      multiple episodes per year (including recurrent brief depression as defined by
      ICD-10) is comparable to major depression by social disability and subsequent
      course in the sample under study.

PMID- 9268775
TI  - Subthreshold depressions: clinical and polysomnographic validation of dysthymic,
      residual and masked forms.
AB  - We summarize clinical and polysomnographic findings in support of the existence
      of a broad and prevalent spectrum of less than syndromal or subthreshold
      depressive conditions that constitute subeffective disorders. Many of these
      conditions were previously subsumed under such rubrics as 'neurotic,'
      'characterological,' and 'existential' depressions. Prospective follow-up studies
      of neurotic depressions (defined by a predominance of the psychological features
      of, in most instances, less than syndromal depression) have demonstrated their
      transformation into moderate to melancholic or psychotic depressive, and even
      bipolar, disorders. Many characterological depressives (outpatients with early
      insidious onset and fluctuating chronicity of subthreshold manifestations falling
      short of full syndromal depression), were shown to have shortened REM latency,
      increased REM%, redistribution of REM to the first part of the night, classic
      diurnality, high rates of family history for mood disorders, positive response to
      antidepressants and sleep deprivation, and prospective follow-up course leading
      to major affective episodes. Shortened REM latency and related sleep
      neurophysiological disturbances have also been reported to characterize so-called
      'borderline' personality disorder even when examined in the absence of
      concomitant major depression. Finally, among primary care referrals to a sleep
      disorders center, short REM latency was found in a large number of patients
      without subjective mood change but with somatic manifestations of depression
      (meeting Probable Feighner Depression and/or lesser subacute manifestations).
      Rather than being incidental, the REM disturbances in the foregoing studies
      appear consistently on consecutive nights of polysomnography in the subthreshold
      affective group; this was not the case for patients with non-affective
      personality and anxiety disorders. The findings overall tend to support a common
      neurophysiological substrate for subthreshold and melancholic depressions and,
      interpreted in the context of clinical observations, family history and follow-up
      course, uphold the validity of dysthymic, intermittent and subsyndromal
      depressions.

PMID- 9268776
TI  - Double depression: a distinctive subtype of unipolar depression.
AB  - Whether depression is a single disease that varies from mild to severe, with
      varying episode durations and difficult course patterns, or whether it is an
      umbrella diagnosis representing depressive subtypes with different psychological
      and biological characteristics has been debated by clinicians and researchers for
      many years. However, most scientists now agree that understanding the
      heterogeneous subtypes of depression allows for greater accuracy in describing
      and differentiating patients suffering from depression and, therefore, greater
      precision in describing the most efficacious treatment plan. This article will
      focus on the distinctions between unipolar major depression, double depression
      and dysthymia, and will review the history of the DSM classifications for these
      "subtypes" of major depressive disorder, clinicians and researchers continue to
      subclassify major depression and, particularly, for the purpose of testing the
      efficacy of new psychopharmocologic and psychosocial treatments. There continues
      to be a need for future research to more clearly establish the predictive value
      in terms of course, recovery, rates of relapse and treatment in regard to
      distinguishing type of depression as well as to validate the current nosology.

PMID- 9268777
TI  - Do psychotic, minor and intermittent depressive disorders exist on a continuum?
AB  - The following paper uses information from a family study and 10-year follow-up of
      probands with unipolar depression to describe relationships between psychotic and
      non-psychotic major depressive disorder (MDD) and, in turn, between psychotic MDD
      and minor or intermittent depressive disorders. Probands began follow-up as they
      sought treatment for MDD at any of five participating academic centers. Follow-up
      evaluations then occurred at 6-month intervals for 5 years and then annually for
      an additional 5 years. Two-thirds of the probands also entered a family study in
      which raters attempted direct interviews of all available adult first-degree
      relatives. Findings that individual symptoms comprising the endogenous MDD
      subtype had higher severity ratings, that the full MDD syndrome was present for a
      greater number of weeks in each year of follow-up, and that time to new episodes
      of MDD were shorter, all indicated that patients with psychotic features had a
      severe variant of MDD. An increased familial risk for psychotic MDD per se, and a
      sustained tendency for psychotic features to recur, indicated an important
      discontinuity, however. The increase in morbidity over time which characterized
      psychotic patients manifested in the full MDD syndrome, but not in mild MDD,
      minor or intermittent depressive syndromes. These milder syndromes tended to be
      more prominent over time among patients who began with non-psychotic MDD. This
      fails to support a continuum spanning both psychotic MDD and the mild,
      subsyndromal forms of unipolar depression.

PMID- 9268778
TI  - The many faces of depression following spousal bereavement.
AB  - While it is becoming increasingly clear that mood disorders tend to be chronic,
      intermittent and/or recurrent conditions with different manifestations over time,
      little is known of the variability or course of mood disorders that are
      associated with severe psychosocial stress. This paper reports on the prevalence
      and course of major, minor, and subsyndromal depressions in 328 widows and
      widowers followed prospectively from 2 to 25 months following one of the most
      disruptive of all naturally occurring stressors, spousal bereavement. The results
      are consistent with the following conclusions: (1) past major depression (prior
      to the death) predicts an increased risk for major depression following
      bereavement; (2) membership in any of the unipolar subgroups, in turn, predicts
      future depression throughout the unipolar depressive spectrum; (3) subsyndromal
      and minor depression stand between major depression, on the one hand, and no
      depression, on the other, in terms of their effects on overall adjustment to
      widowhood. Thus, the results support the validity of subsyndromal depression, and
      that the three subgroups (major, minor and subsyndromal depression) are
      pleiomorphic manifestations of the same unipolar depression disorder.

PMID- 9268779
TI  - All roads lead to depression: clinically homogeneous, etiologically
      heterogeneous.
AB  - Manias, and particularly depressions, are syndromes not disease. Considerable
      data support the fact that depressions, though similar clinically, are of
      heterogeneous etiologies. We can separate depressions generally into those that
      are endogenous/psychotic and those that occur in the context of marked emotional
      instability. Familial pure depressive disease is a specific example of the
      former, depression spectrum diseases a specific example of the latter. These are
      separable on the basis of personality, clinical, follow-up, familial and
      treatment variables.

PMID- 9268780
TI  - Pleomorphic expressions of unipolar depressive disease: summary of the 1996 CINP
      President's Workshop.
AB  - Data presented during the 1996 CINP President's Workshop supported the conclusion
      that unipolar major depressive disorder (MDD) is a pleomorphic mood disorder
      consisting of a cluster of depressive subtypes existing in a relatively
      homogeneous symptomatic clinical continuum, extending from subsyndromal
      depressive symptomatology (SSD) through minor depressive episode, dysthymic
      disorder, major depressive episode and double depression. This indicates that
      common unipolar depressive subtypes can be conceptualized as alternate forms or
      different symptomatic phases of the same parent illness. Although there appears
      to be great overlap across time in the symptomatological expressions of these
      clinical depressive subtypes, they may be derived from different etiological and
      genetic factors. The one exception may be major depressive episode with psychotic
      features, which exists on a severity continuum with other subtypes of unipolar
      MDD, but does not appear to be on a symptomatic continuum with dysthymic,
      subsyndromal or minor depressions. By contrast, SSD and minor depressive disorder
      represent clinically significant depressive subtypes, which are commonly observed
      during the course of illness of patients with unipolar major depressive illness.
      Compared to no depressive symptoms, SSD is associated with harmful dysfunction,
      as evidenced by significant increases in psychosocial impairment, signifying that
      SSD is an active, inter-episode disease state of unipolar major depressive
      disorder. Finally, SSD, possibly jointly with subthreshold anxiety symptoms, may
      also represent potent risk factors for rapid depressive episode relapse. In the
      aggregate, these findings and conclusions have broad and important implications
      for diagnostic and treatment strategies of unipolar MDD.

PMID- 9268781
TI  - Moving toward a core curriculum in Schools of the Allied Health Professions:
      knowledge and skills considered important by department chairs in four
      disciplines.
AB  - An adaptation of the Delphi method was used in four parallel studies to survey
      chairs of baccalaureate programs in clinical laboratory sciences, health
      information management, occupational therapy, and physical therapy in schools of
      the allied health professions which held membership in the Association of Schools
      of the Allied Health Professions. The purpose was to assist the chairs in coming
      to consensus regarding requisite knowledge and skills of graduates beyond those
      required for professional accreditation and credentialing, and prerequisite or
      cognate courses that may be utilized to develop them. Three rounds of
      questionnaires were administered to each group. The final round was completed by
      45 chairs in clinical laboratory sciences (83% of the population); 18 in health
      information management (86%); 18 in occupational therapy (56%); and 24 in
      physical therapy (67%). Statistical analysis of third round responses via one
      sample, one-sided Z tests indicated consensus among the chairs in the four
      disciplines on 16 items of knowledge and skills as most important for graduates.
      Similar consensus was not evident, however, regarding courses to develop the
      knowledge and skills, with only two courses considered most important by all four
      groups of chairs.

PMID- 9268782
TI  - The effect of a computer assisted instructional program on physical therapy
      students.
AB  - The purpose of this study was to assess the efficacy and efficiency of CAI for
      students learning evaluation and treatment skills for carpal tunnel syndrome
      (CTS). Ten volunteer physical therapy students were randomly assigned into either
      CAI or interactive lecture instructional groups. Each student completed a 36-item
      pretest on CTS. The CAI group used the Physical Therapy Patient Simulator CAI and
      the instructional group participated in lecture/discussion to complete the case
      studies. Following completion of instruction, an identical 36 item posttest was
      administered to all students. Individual start and finish times for the two
      groups were recorded by the instructor. A 2 x 2 ANOVA revealed no significant
      difference in pretest/posttest scores between CAI and interactive lecture. A t
      test determined the CAI group completed the case assignment 30 minutes (24%
      faster than the interactive group. The findings suggest that using a CAI
      simulation program may be as effective and more efficient than traditional
      methods of instruction.

PMID- 9268783
TI  - Breaking down barriers: multidisciplinary education model.
AB  - A pilot project was implemented involving students from three disciplines: dental
      hygiene, physical therapy, and physician assistant. The purpose was to prepare
      students to work together in multidiscipline teams utilizing concepts of problem
      based learning (PBL) on both simulated and real patients. The project was divided
      into three phases. Phase I introduced discipline specific information, team
      concepts, and PBL concepts. Phase II involved students working in
      multidisciplinary teams solving a simulated patient case in the PBL format. Phase
      III consisted of students working in small groups and on real patients,
      performing an extraoral/intraoral and periodontal examination, a problem oriented
      physical examination, and a neuromuscular assessment. Pre and posttest evaluation
      of Phase I revealed no difference in knowledge among the three disciplines. Of
      those students evaluating Phase II and III, 100% felt PBL was an effective means
      of presenting multidisciplinary material; 93% reported enhanced problem-solving;
      98% indicated improvements in working in groups; and 98% felt they had learned
      more about each other's discipline. This model may provide a viable means to
      prepare interdisciplinary teams to work effectively together.

PMID- 9268784
TI  - The role of national skill standards in the design of core curriculum in allied
      health.

PMID- 9268785
TI  - Interdisciplinary research class.

PMID- 9268786
TI  - 16- to 25-year follow-up study of cemented arthroplasty of the hip in patients
      aged 50 years or younger.
AB  - The clinical outcome of the cemented Charnley hip arthroplasty at follow-up
      periods of 16-25 years was evaluated retrospectively in patients aged 50 years or
      younger. One hundred thirty-two of a total of 167 hip arthroplasties were
      studied. The overall probability of survival of the implant at 20 years was 75%
      Survival of those with rheumatoid disease was 80% compared with 64% for those
      with osteoarthritis. Female sex was associated with a better prognosis.
      Accelerated wear was associated with decreased survival of the prosthesis. Varus
      orientation of the femoral component significantly influenced failure (P < .01).
      Radiographic loosening of the acetabular component was well tolerated, but
      loosening of the femoral component was significantly associated with pain (P =
      .01).

PMID- 9268787
TI  - Unsatisfactory results of a first-generation modular femoral stem implanted
      without cement. A 4- to 9-year follow-up study.
AB  - Eighty primary total hip arthroplasties were performed using a first-generation
      modular femoral stem inserted without cement. Modular distal sleeves made of
      methacrylate were used in 33% of the hips. Dorr type B or C femoral geometry was
      present in 80% of the cases. The mean follow-up period was 81 months with a
      minimum of 48 months. Satisfactory clinical results were observed in 74% of the
      hips at the final follow-up visit. Revision of the stem had been performed in 14%
      of the hips, all for aseptic loosening. The overall mechanical failure rate was
      48%. Canal fill by the stem was not any better with the sleeves than without. The
      incidence of failure, however, was less in those hips in which sleeves were used.
      Femoral osteolysis was present in 19% of the hips. The experience with this
      particular stem design has been disappointing.

PMID- 9268788
TI  - Safety and efficacy of bilateral total knee arthroplasty.
AB  - Recent studies have reported increased morbidity associated with bilateral
      simultaneous total knee arthroplasty (TKA). The purpose of this study was to
      evaluate the morbidity and clinical outcome associated with simultaneous
      bilateral TKA in contrast to unilateral TKA. All primary TKAs, either unilateral
      or simultaneous bilateral, performed between May 1988 and July 1993 were
      retrospectively reviewed. Patients were evaluated using Knee Society scores both
      before surgery and a minimum of 6 months after surgery. In addition to routine
      demographics, patients were evaluated for the incidence of both local wound and
      systemic complications. It is concluded that performing simultaneous bilateral
      TKA does not result in any significant increase in patient morbidity or
      compromise in postoperative function when compared with unilateral TKA.

PMID- 9268789
TI  - Bone-graft augmentation for acetabular deficiencies in total hip arthroplasty.
      Results of long-term follow-up evaluation.
AB  - The results of 102 consecutive primary and revision total hip arthroplasties
      performed with bone-grafting for acetabular bone deficiencies were reviewed at an
      average of 10.2 years (range, 4-18.6) after surgery. Ninety-one percent had
      structural bone defects and 57% had underlying developmental dysplasia of the
      hip. Overall acetabular revision rates for aseptic loosening were 8% at 5 years
      and 26% at 10 years. In addition, in the patients with developmental dysplasia
      who had primary hip arthroplasties, acetabular revision rates for aseptic
      loosening were 3 and 18% at 5 and 10 years, respectively. Ninety-six percent of
      all uninfected grafts incorporated. Bulk grafts fared better than particulate
      grafts. No difference in failure rate was noted between primary and revision hip
      arthroplasty, type of deficiency, or amount of graft coverage. Although early
      results are encouraging, acetabular failure increased significantly with longer
      follow-up evaluation; however, graft incorporation was successful and facilitated
      subsequent revision surgery.

PMID- 9268790
TI  - Postoperative blood salvage and reinfusion after total joint arthroplasty.
AB  - The purpose of this prospective study was to evaluate the safety of salvage and
      reinfusion of postoperative sanguineous wound drainage using the ConstaVac Blood
      Conservation System (Stryker, Kalamazoo, MI). A prospective analysis of 135
      primary total hip and total knee arthroplasties was carried out. The collection
      time for reinfusion was limited to 6 hours, and suction pressure was kept to a
      minimum by using the lowest setting on the device. For all patients, no citrate
      phosphate-dextrose anticoagulant was added to the reservoir. To evaluate the
      effect of reinfusion on hemostasis and the blood coagulation system, antithrombin
      III, fibrinogen, and D-dimer levels of 40 of 135 patients were measured before
      surgery and on the first and seventh days after the operation. The mean volume of
      reinfusion of postoperative drainage was 437 mL for the patients with total hip
      arthroplasties, 883 mL for those with total knee arthroplasties, and 1,713 mL for
      those with bilateral total knee arthroplasties. Ninety-nine of 135 patients
      underwent operations without homologous blood replacement. Transient chills with
      mild fever were seen in 2 patients during reinfusion. No complications related to
      air embolism, coagulopathy, renal failure, or sepsis were recognized in any of
      the patients. This study suggests that postoperative blood salvage and reinfusion
      appear to be safe and effective in patients undergoing primary total hip and knee
      arthroplasties.

PMID- 9268791
TI  - Autotransfusion after total knee arthroplasty. Effects on blood cells, plasma
      chemistry, and whole blood rheology.
AB  - Postoperative drain blood was collected and reinfused using the ConstaVac system
      (Stryker, Kalamazoo, MI) in 30 patients after total knee arthroplasty. Of the
      total 1.1-L volume of postoperative bleeding, 60% was reinfused. No clinical
      complications were observed. Differences between venous blood and drain blood and
      between venous blood and drain blood after separate incubation were studied with
      respect to acidic and inflammatory effects on blood cells, plasma chemistry, and
      whole blood rheology. In drain blood, leukocyte and platelet counts were reduced
      (P < .001), probably as a result of consumption in the wound. Acidic incubation
      occurs in the drain container because of production of lactate from glucose, with
      a minimum pH at 5 hours of 7.2. The low pH caused slight but significant
      erythrocyte swelling (P < .01). The complement C3d indicated leukocyte
      activation, although of modest magnitude. Despite incubation and complement
      activation, maximum erythrocyte hemolysis after 24 hours of incubation was less
      than 1%. Drain blood showed a lower resistance against micropore filtration than
      venous blood (P < .001), mainly because of the reduced number of leukocytes, and
      remained unchanged with incubation. Although the autotransfusion system can be
      improved with respect to blood quality, filtered drain blood should be considered
      acceptable for reinfusion.

PMID- 9268792
TI  - Impact of declining reimbursement and rising hospital costs on the feasibility of
      total hip arthroplasty.
AB  - Total hip arthroplasty, although a very successful clinical treatment, remains an
      expensive procedure in an era of constrained health care resources.
      Hospitalization cost, charge, and reimbursement data were compared between all
      patients who underwent elective, primary, unilateral total hip arthroplasty in
      1988 and 1993 at the UCLA Medical Center. Although length of hospitalization
      decreased by 36%, increases both in unit supply costs and in the intensity of
      hospital services prevented a statistically significant reduction in total
      hospitalization cost. Reimbursement declined by 27% after calculating inflation
      with the Consumer Price Index for Medical Care. Further, the margin by which
      reimbursement exceeded cost decreased from 66% in 1988 to 8% in 1993. These
      trends constitute a serious threat to the financial feasibility of total hip
      arthroplasty.

PMID- 9268793
TI  - Massive early subsidence following femoral impaction grafting.
AB  - The incidence of massive early subsidence (subsidence greater than 10 mm)
      following impaction grafting of the femur in revision surgery is reported. The
      first 79 consecutive revision total hip arthroplasties using morselized
      allograft, polymethyl methacrylate cement, and a double-tapered, polished,
      collarless stem were reviewed. Nine (11%) of the 79 revision femoral prostheses
      showed massive subsidence, with another nine hips subsiding to a lesser degree.
      Further elucidation of the critical factors contributing to the initial stability
      of the biologic composite is required.

PMID- 9268794
TI  - Comparison of joint position sense after total knee arthroplasty.
AB  - A comparison of joint position sense, determined by reproducibility of index
      angles and their subsequent change, was performed in 55 knees that had undergoing
      a semiconstrained total knee arthroplasty. Knees were stratified into groups that
      represented arthroplasties performed with or without posterior cruciate ligament
      retention, with or without resurfacing of the patella, and with or without cement
      for fixation. There was no significant difference in joint position sense among
      all the arthroplasty groups. Likewise, there was no difference in joint position
      sense between any of the arthroplasty groups and an age-matched control group of
      32 knees in 32 patients who had not previously undergoing a total knee
      arthroplasty. Knee arthroplasty does not affect joint position sense.

PMID- 9268795
TI  - Intra-articular morphine and/or bupivacaine in the management of pain after total
      knee arthroplasty.
AB  - The purpose of this study was to determine if intra-articular injection of
      morphine or bupivacaine significantly decreased postoperative pain as well as the
      use of intravenous narcotics for pain relief in patients undergoing total knee
      arthroplasty (TKA). In a prospective, double-blind, randomized fashion, 105
      patients undergoing TKA were divided into the following 4 groups defined by the
      intra-articular injection they received: group 1 (n = 27) received saline
      solution, group 2 (n = 26) received morphine sulfate (5 mg), group 3 (n = 24)
      received bupivacaine (50 mg), and group 4 (n = 28) received a combination of
      morphine sulfate and bupivacaine. The injections were administered immediately
      after wound closure by the Hemovac drainage tubing that remained clamped for 45
      minutes after surgery to allow for absorption. Before surgery and at 2, 4, 6, 24,
      and 48 hours after surgery, pain intensity was recorded using a visual analog
      scale. Postoperative supplemental intravenous morphine and/or meperidine was
      administered via a patient-controlled analgesia device, and 24-hour drug usage
      was tabulated. Results were suggestive of a modest short-term reduction in pain
      scores in the morphine and bupivacaine treatment groups compared with placebo
      (saline); however, results were statistically significant only at 4 hours because
      of the great variability in the pain score data. The total amount of
      postoperative pain medication used in the first 24 hours after surgery was not
      statistically significant between the 4 treatment groups. Thus, the results put
      into question the benefit of postoperative intra-articular administration of
      morphine or bupivacaine in patients undergoing TKA.

PMID- 9268796
TI  - Rollback in posterior cruciate ligament-retaining total knee arthroplasty. A
      radiographic analysis.
AB  - A clinical and radiographic study of 49 posterior cruciate ligament-retaining
      total knee arthroplasties in 38 patients (11 bilateral, 27 unilateral), using
      prostheses of the same design, was undertaken to quantify the amount of in vivo
      rollback (ie, the anteroposterior translation of the tibia with respect to the
      femur during flexion). The mean difference in the distances between the contact
      points of the knees in full extension and in 90 degrees flexion (ie, the rollback
      distance) was a posterior translation of the contact point of -0.2 mm (-12.7 to
      +7l6 mm; SD, 4.7 mm) relative to the prosthetic tibial tray, corresponding to an
      average translation of 0% of the prosthetic tibial tray depth, and -0.2 mm (-12.5
      to +9.1 mm; SD, 4.8 mm) relative to the tibia itself, corresponding to an average
      translation of 0% of the true tibial surface depth. The differences between the
      rollback values obtained from the 90 degrees and full-extension radiographs
      relative to the prosthetic tibial tray (P = .63) and the true tibia (P = .89)
      were not statistically significant. Intraobserver (P = .27-.50) and interobserver
      (P = .13-.72) reliability tests showed that the differences between radiographic
      measurements taken by the same observer at two different points in time and by
      two different observers were not statistically significant. No correlations were
      found between the degree of translation of the tibiofemoral contact point
      relative to the prosthetic tibial tray and the posterior tilt of the tibial tray
      (R2 = .12), the preoperative tibiofemoral angle (R2 = .34), and the postoperative
      tibiofemoral angle (R2 = .027). No correlations were found between the degree of
      translation of the tibiofemoral contact point relative to the true tibia and the
      posterior tilt of the tibial tray (R2 = .16), the preoperative tibiofemoral angle
      (R2 = .14), and the postoperative tibiofemoral angle (R2 = .034). In conclusion,
      this study indicated no demonstrable rollback occurring in the posterior cruciate
      ligament-retaining total knee arthroplasty used in this study.

PMID- 9268797
TI  - Human postmortem retrieval of total hip arthroplasty.
AB  - Postmortem retrieval of well-functioning prostheses from total hip arthroplasty
      is essential in determining the quality and success of the implant, implant
      fixation, and operative technique. This report describes the retrieval procedure,
      including details on informed consent, retrieval procedure, and types and
      benefits of specimen analysis. Bone densitometry, roentgenography, and microscopy
      studies permit a level of assessment of operative and prosthetic performance not
      obtainable from clinical and in vivo roentgenographic evaluation alone. Findings
      from these techniques yielding data on stress shielding, bone mineral density,
      extent of bone-prosthesis apposition and osseointegration, and histologic
      activity are ultimately of considerable clinical significance. The implementation
      of retrieval programs, along with establishing early family and patient
      cooperation and proper planning practices, will continue to contribute invaluably
      to advances in orthopaedic science.

PMID- 9268798
TI  - Vastus-Psoas release for acetabular exposure in revision hip surgery.
AB  - A technique is presented for wide exposure of the acetabulum for revision total
      hip arthroplasty surgery in the presence of a solidly fixed, modular, or
      monoblock femoral component without the need for trochanteric osteotomy. The
      technique involves release of the proximal portion of the vastus lateralis,
      vastus intermedius, and vastus medialis muscles and the iliopsoas tendon form the
      femur and placement of the femoral head/neck posterior to the acetabulum. The
      exposure afforded by this release usually precludes the need for trochanteric
      osteotomy and/or removal of a well-fixed femoral component in revision surgery
      that is being done for isolated loosening of acetabular components, thereby
      decreasing operative time, morbidity, and the risks of complication of
      trochanteric osteotomy.

PMID- 9268799
TI  - Application of magnets in total knee arthroplasty surgery.

PMID- 9268800
TI  - One-stage reconstruction of skin defect and patellar tendon rupture after total
      knee arthroplasty. A new technique.
AB  - A case is presented herein in which infected total knee arthroplasty associated
      with a skin defect and patellar tendon rupture was reconstructed with lateral
      gastrocnemius-Achilles tendon complex after infection was controlled. The results
      were satisfactory, and the technique proposed herein is highly promising for
      treating such complicated circumstances after total knee arthroplasty, as not
      reported previously.

PMID- 9268801
TI  - Subtrochanteric stress fracture of the femur following total knee arthroplasty.
AB  - This study reports the first case of a subtrochanteric stress fracture of the
      femur after total knee arthroplasty. A 61-year-old obese woman was treated by
      right total knee arthroplasty for osteoarthrosis. Four months after the surgery
      and 1 month after full weight bearing, she complained of tenderness in the right
      groin and proximal thigh. There was no history of trauma. Radiographs of the
      right hip and of the right proximal femur were interpreted as unremarkable, and
      nonsteroid anti-inflammatory drugs were administered. Three months later, she had
      a sudden onset of increased pain with instability and giving way of the right
      leg. Radiographs revealed a subtrochanteric transverse fracture of the right
      femur. Histologic workup of the bone and tissue specimen taken at open reduction,
      as well as the laboratory data were consistent with the radiologic and clinical
      diagnosis of a stress fracture. It is most likely that a decrease in the tension
      band effect of the iliotibial tract in combination with coxa vara and changes in
      static and dynamic forces of the femur and an increased level of activity after a
      period of relative inactivity secondary to the knee arthroplasty are responsible
      for this very uncommon fracture type.

PMID- 9268802
TI  - 46-year survival of a Smith-Petersen mold arthroplasty.
AB  - The case, of a patient who is believed to be the longest surviving person with a
      hip arthroplasty is reported. The patient is still pleased with the function of
      the Smith-Petersen arthroplasty 46 years following its insertion, and has
      declined revision to a total hip arthroplasty.

PMID- 9268803
TI  - Unusual cause of third-body wear in total hip arthroplasty.
AB  - A case of severe osteolysis caused by third-body wear using a Harris-Galante II
      cup (Zimmer, Warsaw, IN) is reported. The prosthesis was inserted in a 23-year
      old man 4.5 years ago. At revision, 3 triangular tynes of the acetabular shell
      rim were found embedded in the polyethylene liner.

PMID- 9268804
TI  - Dislodgement of the femoral component of a total hip arthroplasty presenting
      through the buttock.
AB  - The end result of nonsurgical management of the infected loose femoral component
      of a total hip arthroplasty is presented. This is the expulsion from the body of
      the foreign material.

PMID- 9268805
TI  - Revision total hip arthroplasty with correctional femoral osteotomy in Paget's
      disease.
AB  - Varus alignment of the femoral component is associated with femoral component
      loosening in total hip arthroplasty performed for Paget's disease. Irregular and
      hemorrhagic bone, along with angular femoral deformity, was encountered during
      revision total hip arthroplasty in three pagetic patients. A diaphyseal femoral
      osteotomy facilitated cement removal and provided an opportunity for correction
      of the deformity. The step-cut configuration of the osteotomy provided intrinsic
      rotational stability of the femoral segments around a modular, long-stem
      cementless implant. Excellent clinical and radiographic results were achieved,
      but moderate blood loss and delayed healing of the osteotomy site were observed.

PMID- 9268806
TI  - A new method of treatment for periprosthetic supracondylar fractures of the femur
      for prostheses with a stemmed femoral component.
AB  - Knee arthroplasty periprosthetic supracondylar fracture of the femur is a well
      recognized problem that is likely to be seen more frequently with the increasing
      number of knee arthroplasties being performed. Treatment of this fracture is
      difficult. A new method of internal fixation for supracondylar fractures around a
      stemmed femoral component using a custom-made extension to the femoral stem is
      described. This technique allowed early mobilization of the patient, with
      restoration of a good range of movement of the knee and fracture union within 1
      year.

PMID- 9268807
TI  - Auditory ERPs during rhyme and semantic processing: effects of reading ability in
      college students.
AB  - Event-related potential (ERP), reaction time (RT), and response accuracy measures
      were obtained during the phonological and semantic categorization of spoken words
      in 14 undergraduates: 7 were average readers and 7 were reading-impaired. For the
      impaired readers, motor responses were significantly slower and less accurate
      than were those of the average readers in both classification tasks. ERPs
      obtained during rhyme processing displayed a relatively larger amplitude
      negativity at about 480 ms for the impaired readers as compared to the average
      readers, whereas semantic processing resulted in no major group differences in
      the ERPs at this latency. Also, N480 amplitude was larger during semantic
      relative to phonological classification for the average readers but not for the
      impaired readers. Results are compared to a previous study of reading-impaired
      children on the same tasks.

PMID- 9268809
TI  - The Post-Stroke Depression Rating Scale: a test specifically devised to
      investigate affective disorders of stroke patients.
AB  - Owing to the lack of instruments specifically constructed to study emotional and
      affective disorders of stroke patients, the nature of post-stroke depression
      (PSD) remains controversial. With this in mind, the authors constructed a new
      scale, the Post-Stroke Depression Scale (PSDS) which takes into account a series
      of symptoms and problems commonly observed in depressed stroke patients. The PSDS
      and the Hamilton Depression Rating Scale (HDS) were administered to a group of
      124 patients, who had been classified, on the basis of DSM III-R diagnostic
      criteria, in the following categories: No depression (n = 32); Minor PSD (n =
      47); Major PSD (n = 45). Scores obtained by these stroke patients on the PSDS and
      on the HDS were compared to those obtained on the same scales by 17 psychiatric
      patients also classified as major depression on the basis of DSM III-R diagnostic
      criteria. An analysis of the symptomatological profiles clearly showed that: (1)
      a continuum exists between the so-called "major" and "minor" forms of PSD; (2) in
      both groups of depressed stroke patients the depressive symptomatology seems due
      to the psychological reaction to the devastating consequences of stroke, since
      the motivated aspects of depression prevailed in depressed stroke patients,
      whereas the (biologically determined) unmotivated aspects prevailed in patients
      with a functional form of major depression; and (3) in stroke patients a DSM III
      based diagnosis of major PSD could be in part inflated by symptoms (such as
      apathy and vegetative disorders) that are typical of major depression in a
      patient free from brain damage, but that could be due to the brain lesion per se
      in a stroke patient.

PMID- 9268808
TI  - Cross-cultural neuropsychological assessment: a comparison of randomly selected,
      demographically matched cohorts of English- and Spanish-speaking older adults.
AB  - As the US population of elderly Hispanics continues to grow, there is an
      increasingly greater need for neuropsychological measures that are appropriate
      for assessing Spanish-speaking elders. The current study compared the performance
      of randomly selected, community-based samples of English- and Spanish-speaking
      elders on a brief neuropsychological test battery. Subject groups were matched
      for age and education. Multivariate analysis indicated significant group
      differences on the test battery. English and Spanish speakers scored comparably
      on many language-based tasks, but Spanish speakers scored significantly lower on
      almost all of the nonverbal measures. Significant group differences were observed
      on multiple-choice matching and recognition memory for stimuli from the Benton
      Visual Retention Test, as well as on Identities and Oddities from the Mattis
      Dementia Rating Scale, category fluency, and Complex Ideational Material from the
      Boston Diagnostic Aphasia Examination (BDAE). Results suggest that caution is
      warranted when using nonverbal as well as verbal measures to assess non-English
      speaking individuals.

PMID- 9268810
TI  - Memory for verbal information in individuals with HIV-associated dementia
      complex. HNRC Group.
AB  - Patterns of memory performance were examined for 9 participants with HIV
      associated dementia (HAD), 15 HIV-seropositive participants without dementia, and
      15 HIV-seronegative controls. Episodic and semantic memory were assessed using
      the California Verbal Learning Test, the Boston Naming Test, and Verbal Fluency
      tests. The HAD group showed deficits in episodic memory, with relative sparing of
      semantic memory. In addition, results suggest a retrieval deficit in HAD rather
      than a deficit in retention of information. This pattern is consistent with the
      presence of a subcortical dementing process and supports findings from previous
      neuropathological, neuroimaging, and neuropsychological studies suggesting that
      subcortical brain dysfunction is frequently associated with HIV disease (e.g.,
      Navia, Jordan, & Price, 1986).

PMID- 9268811
TI  - Effect of directed attention in Huntington's disease.
AB  - This experiment sought to ascertain whether overt gaze (i.e., directed attention)
      would influence attentional performance in Huntington's disease (HD), via the use
      of a vibrotactile choice reaction time procedure involving biased probabilities
      of event occurrence. Subjects looked (i.e., direct gaze) either at the hand
      receiving the most (expected) vibrations, or the hand less often stimulated (the
      unexpected), for both crossed and uncrossed arm postures. Patients with HD showed
      performance advantages when directing attention (i.e., gaze) at the responding
      hand, especially for expected events. Patients with HD, however, were not
      sensitive to distributions of event probability in the uncrossed arm posture, nor
      when looking away from the responding hand. With the crossed arm posture, and
      when directing attention at the expected side, patients with HD became more
      sensitive to distributions of event probability. In HD, there may be a disruption
      of fronto-striatal circuitry on both cortical and subcortical levels which may
      account for impairments both in holding and shifting attention.

PMID- 9268813
TI  - Concurrent validity of the Neurobehavioral Cognitive Status Exam subtests.
AB  - The Neurobehavioral Cognitive Status Exam (NCSE) is a screening measure that
      assesses numerous neuropsychological (NP) domains. Fifty-four patients completed
      the NCSE and common NP tests assessing similar abilities. Most subtest screens
      (brief items that determine whether additional testing should occur) exhibited
      low false negative rates, but high false positive rates, based upon performance
      on the follow-up metric items. Each subtest was significantly correlated with the
      associated NP test. However, using performance on the NP tests as the 'gold
      standard', the NCSE subtests classified impaired and unimpaired patients at a
      much lower than expected rate. The latter results draw into question the efficacy
      of the NCSE subtests in delineating domain-specific cognitive functioning.

PMID- 9268812
TI  - Effects of abstinence and relapse upon neuropsychological function and cerebral
      glucose metabolism in severe chronic alcoholism.
AB  - Prolonged excessive consumption of alcohol has been associated with a variety of
      cognitive disorders accompanied by neuropathological and neurochemical
      abnormalities of the brain, particularly in the frontal lobes. Studies with
      positron emission tomography (PET) have shown decreased local cerebral metabolic
      rates for glucose (lCMRglc) in frontal regions, with correlated abnormalities on
      neuropsychological tests sensitive to executive functioning. This investigation
      was designed as a pilot study to examine the effects of abstinence and relapse in
      patients with severe chronic alcoholism studied longitudinally with PET and with
      neuropsychological evaluation to assess both general and executive functioning.
      Six patients, including 4 who remained relatively abstinent and 2 who relapsed
      following their initial evaluation, were studied twice, with inter-evaluation
      intervals ranging from 10 to 32 months. The patients who remained abstinent or
      who had minimal alcohol use showed partial recovery of lCMRglc in two of three
      divisions of the frontal lobes and improvement on neuropsychological tests of
      general cognitive and executive functioning, whereas the patients who relapsed
      had further declines in these areas. These results, although based upon a
      relatively small number of subjects, provide preliminary support for at least
      partial recovery of metabolic and cognitive functioning in individual patients
      who abstain from alcohol.

PMID- 9268814
TI  - Influence of seizure content on interpreting psychopathology on the MMPI-2 in
      patients with epilepsy.
AB  - We investigated whether seizure content items inflate MMPI-2 scores in persons
      with epilepsy. A mean MMPI-2 profile was generated for 100 epilepsy patients. Two
      expert raters then identified MMPI-2 items reflecting seizure symptoms. When
      individual profiles were rescored to remove elevations caused by seizure content,
      some statistically significant (but not clinically significant) decreases were
      observed. The MMPI-2 appears to be a valid assessment instrument in epilepsy. In
      most cases seizure content did not alter clinical interpretation. When the
      interest is in detecting symptom change, assessing both statistical and clinical
      significance is recommended in future MMPI-2 research.

PMID- 9268815
TI  - Color-Word Stroop test performance across the adult life span.
AB  - In the Color-Word Stroop test (CWST), the basic task is to name the ink color of
      rows of XXXs, and performance in this condition is compared with performance in
      naming the ink-color of color words under conditions where word meanings and ink
      colors mismatch or are incongruent (e.g., the word red printed in green ink). The
      present study investigated whether Stroop test interference, defined as the cost
      associated with ink-color naming in the incongruous stimulus condition versus in
      the basic color-naming condition, provides positive evidence for a kind of
      processing qualitatively different than that which is required for color naming
      or for word reading. Does the pattern of age-related differences in Stroop
      interference force the conclusion that the incongruous condition taps a
      qualitatively different kind of processing than that required for color naming or
      for word reading? We gave the CWST to 310 healthy adults. Their performance in
      each condition of the test replicates and extends previous findings. Structural
      equation modeling of the data showed a significant, direct link between age and
      performance in the latent factor associated with the incongruent condition.
      However, this direct link with age produced a relatively small increase in the
      model's fit; it amounted to only a .024 increase in the proportion of variance
      explained in the incongruent condition. In light of this small direct influence
      due to age, the most parsimonious explanation of our findings is that age effects
      in Stroop interference are due to age-related slowing (which is also indexed by
      color naming and by word reading) primarily; the findings do not provide evidence
      for a qualitatively different kind of processing that declines with age.

PMID- 9268816
TI  - A review of mild head trauma. Part I: Meta-analytic review of neuropsychological
      studies.
AB  - We conducted a meta-analytic review of neuropsychological studies of mild head
      trauma (MHT). Studies were included if they met these criteria: patients studied
      at least 3 months after MHT; patients selected because of a history of MHT rather
      than because they were symptomatic; and attrition rate of less than 50% for
      longitudinal studies. Studies of children were not considered. We found a total
      of 8 published papers with 11 samples that met these criteria. Using the g
      statistics, the overall effect size of 0.07 was nonsignificant, but the d
      statistic yielded an effect size of 0.12, p < .03. Measurers of attention had the
      largest effect, g = 0.17. p < .02 and d = 0.20, p < .006. Severity of injury
      accounted for far more variance than did specific neuropsychological domain,
      however. The small effect size suggests that the maximum prevalence of persistent
      neuropsychological deficit is likely to be small and neuropsychological
      assessment is likely to have positive predictive value of less than 50%.
      Consequently, clinicians will more likely be correct when not diagnosing brain
      injury than when diagnosing a brain injury in cases with chronic disability after
      MHT.

PMID- 9268818
TI  - Effect on measurement error on tests of statistical significance.
AB  - Using the domain-sampling model from classical test theory, the effects of
      measurement error on statistical tests for the difference between an obtained
      mean and a hypothesized mean, and the difference between two means, are
      demonstrated. The results indicate that lowering the reliability (i.e.,
      increasing measurement error) of dependent variable data increases the chance of
      obtaining a nonsignificant result when a significant result is the correct
      outcome. Lowering the reliability also produces reduced estimates of strength of
      association.

PMID- 9268817
TI  - A review of mild head trauma. Part II: Clinical implications.
AB  - In Binder et al. (1997) a metal-analytic review revealed a small effect size
      attributable to a history of mild head trauma (MHT). The results suggested a weak
      association between MHT and persistent neuropsychological deficits. In this
      paper, additional outcome data are summarized and the results are discussed. On a
      chronic basis, 7-8% of MHT patients remain symptomatic and 14% are disabled from
      work. Magnetic resonance studies of acutely injured persons may show lesions that
      are not detected in usual clinical practice. It is likely that the effects of
      these lesions dissipate with time, consistent with the neuropsychological data.
      The association between MHT and cognitive deficits, symptoms, and disability may
      not be casual; data suggest that MHT patients have more psychosocial problems
      prior to injury than do non-injured persons. The examiner of the MHT patient with
      chronic complaints must consider alternative medical and psychiatric explanations
      and perform a differential diagnosis. The possibility of a neurological basis for
      sustained neuropsychological problems cannot be completely dismissed. Presently,
      however, there is little evidence for neurological causation of most persisting
      complaints.

PMID- 9268819
TI  - Digital imaging and communications in medicine in 1997: an update.

PMID- 9268820
TI  - Strategic thinking for radiology.
AB  - We have now analyzed the use and benefits of four Strategic Thinking Tools for
      Radiology: the Vision Statement, the High Five, the Two-by-Two, and Real-Win
      Worth. Additional tools will be provided during the tutorial. The tools provided
      above should be considered as examples. They all contain the 10 benefits outlined
      earlier to varying degrees. It is extremely important that the tools be used in a
      manner consistent with the Vision Statement of the organization. The specific
      situation, the effectiveness of the team, and the experience developed with the
      tools over time will determine the true benefits of the process. It has also been
      shown that with active use of the types of tools provided above, teams have
      learned to modify the tools for increased effectiveness and have created
      additional tools for specific purposes. Once individuals in the organization
      become committed to improving communication and to using tools/frameworks for
      solving problems as a team, effectiveness becomes boundless.

PMID- 9268821
TI  - Quality assurance for digital imaging.

PMID- 9268823
TI  - Evaluating a picture archiving communication system workstation.

PMID- 9268822
TI  - Image data compression.
AB  - The tutorial will expand on all of the topics outlined above and will provide
      additional information on other compression techniques. The practical
      implications of data compression and the important considerations in choosing a
      compression scheme will also be discussed. Development of new compression
      algorithms remains an active area of investigation and will continue to increase
      the degree of compression possible.

PMID- 9268824
TI  - Real world teleradiology.

PMID- 9268825
TI  - Teleradiology legal issues.

PMID- 9268827
TI  - Designing a request for proposal for picture archiving and communication system.

PMID- 9268826
TI  - US Food and Drug Administration's regulation of software and picture archiving
      and communication systems.

PMID- 9268828
TI  - Issues in multimodality medical image registration.

PMID- 9268829
TI  - The use of intranets and extranets in radiology.

PMID- 9268830
TI  - Telemedicine: a guide to assessing telecommunications in healthcare.

PMID- 9268831
TI  - The future of the picture archiving communication system.

PMID- 9268832
TI  - Update on Internet and advanced telecommunications in telemedicine.

PMID- 9268834
TI  - Picture archive and communication systems implementation in a community medicine
      practice.
AB  - In order to gain experience with vendor-supplied picture archive and
      communication system (PACS) products, a Vantage PACS from Lockheed-Martin was
      installed in a Mayo community medicine practice in Rochester. This practice
      produces about 45,000 radiology examinations annually. The PACS includes central
      long- and short-term storage devices, 10 image display workstations, and a
      dedicated high-speed image distribution network. Digital images are produced
      using two Fuji computed radiography readers. Custom worklists were created to
      facilitate efficient system usage. Currently, all radiographic examinations for
      this practice are acquired digitally, and interpreted and distributed using the
      PACS. Remote softcopy interpretation via PACS has decreased the turnaround time
      for both routine and urgent examinations, and has allowed subspecialty
      interpretation or consultation for pediatric examinations. These results have
      significantly improved the radiology component of this community medicine
      practice.

PMID- 9268833
TI  - Patient-specific anatomic models from three dimensional medical image data for
      clinical applications in surgery and endoscopy.
AB  - Virtual surgery and endoscopy use computer-generated volume renderings and/or
      models created from 3D medical image scans (CT or MRI) of individual patients.
      The patient's anatomy, including organs and other internal structures of
      interest, are then traversed in a virtual "fly-through," giving nearly the same
      visual impression as if the corresponding real organ was being examined
      intraoperatively, or as if an actual video or fiberoptic endoscopic procedure was
      being performed. Such virtual examinations may provide capabilities and
      information not possible or available in physical examinations. The potential is
      to provide a noninvasive computer-aided treatment plan or diagnostic screening
      procedure to augment or replace conventional invasive procedures. With
      sophisticated image processing and computational analysis, it is possible to
      perform realistic and useful simulations of surgical and endoscopic procedures,
      including "virtual dissection and resection" and "virtual biopsy." Surgical
      margins can be accurately assessed and differential tissue diagnoses made based
      upon spectral or other information contained in the patient-specific images and
      models.

PMID- 9268835
TI  - Image display for clinicians on medical record workstations.
AB  - Image display on electronic medical record (EMR) workstations is an important
      step in widespread implementation of picture archiving and communications systems
      (PACS). We describe a pilot project for implementing image display capability
      that is integrated with the EMR software, and will allow display of images on the
      physician's workstation. We believe this pilot will provide valuable information
      about usage patterns in image display needs, which will be valuable in planning
      further expansion of PACS in our institution.

PMID- 9268836
TI  - Patterns of utilization of computer workstations in a filmless environment and
      implications for current and future picture archiving and communication systems.

PMID- 9268837
TI  - Highlights of the Digital Imaging Network-Picture Archiving and Communications
      System Project.
AB  - The Department of Defense issued its requirements for a Digital imaging Network
      Picture Archiving and Communications System (DIN-PACS) in a Request for Proposals
      to industry in January, 1997. The DIN-PACS shall be an open systems network of
      digital devices designed for the effective acquisition, transmission, display and
      management of diagnostic imaging studies. This network is primarily based on two
      international standards, Digital imaging and Communications in Medicine (DICOM)
      and Health Level 7 (HL7). The DIN-PACS is required to communicate in a
      bidirectional manner with the Department of Defense standard hospital information
      system called the Composite Health Care System (CHCS) through an HL7 compliant
      interface. The DIN-PACS model and its published specifications stress
      functionality and performance rather than system architecture to allow industry
      to propose optimal approaches for implementation. This paper discusses the
      functional requirements of the DIN-PACS in terms of its internal operations as
      well as its communication with external systems and components. This is a US
      government work. There are no restrictions on its use.

PMID- 9268838
TI  - Initial experience with soft-copy display of computed radiography images on three
      picture archive and communication systems.
AB  - We recently installed picture archive and communication systems (PACS) from three
      different vendors on our campus for evaluation. A major part of this evaluation
      involved assessing the capabilities of these systems for displaying computed
      radiography (CR) images for primary interpretation. The three PACS provided
      different functionality for CR image display in terms of availability of the
      proprietary Fuji CR image processing algorithms, availability of user-specified
      contrast look-up tables, and application of the processing at the time of CR
      image capture or image display. We found that the Fuji processing algorithms were
      important for printing film, but were not necessary for acceptable soft-copy
      display. Non-linear contrast processing produced superior results compared to
      simple linear processing (via standard window width and level controls). Display
      processing was best applied immediately prior to the display operation, as
      opposed to at the image capture time. This allows the display to be adjusted to
      demonstrate the full 10-bit range of the CR image, and also allows raw CR data
      (i.e. not optimized for any particular display device) to be stored in the long
      term archive.

PMID- 9268839
TI  - Evaluating virtual endoscopy for clinical use.
AB  - Virtual endoscopy is a term used to describe computer simulated endoscopy
      procedures derived from high resolution images of patient anatomy. By simulating
      the endoscopic examination, the patient is spared the discomfort and possible
      complications of an actual examination. The physician also has more flexibility
      in a virtual endoscopic examination of 3D patient data in comparison to a real
      endoscopic examination. Virtual endoscopy removes the physical and physiologic
      constraints of real endoscopy and can create views that are not possible in an
      actual endoscopic examination. This may enhance the performance of actual
      endoscopic examinations. Virtual endoscopy may also be used to perform "numerical
      biopsies"; anatomic measurements such as size, distance, shape, and density.
      Virtual endoscopy allows the physician to comprehensively explore the patient
      anatomy using an intuitive and interactive interface. There are currently two
      technical approaches to performing virtual endoscopy: perspective volume
      rendering and surface rendering of polygonal models. Perspective volume rendering
      uses traditional volumetric rendering algorithms to create visualizations
      directly from the volumetric dataset. Polygonal models require a preprocessing
      step to convert the segmented volume information into a polygonal surface that
      may be displayed at real time frame rates. Both paradigms have inherent strengths
      and weaknesses. We illustrate and compare the methods on actual patient data,
      including simulated endoscopic examinations of the airways, colon and esophagus.
      Preliminary results in virtual endoscopy show promise and will continue to be an
      area of active research leading to useful clinical applications.

PMID- 9268840
TI  - Image BOSS: an image database system designed for research.

PMID- 9268841
TI  - An analytical look at the effects of compression on medical images.
AB  - This article will take an analytical look at how lossy Joint Photographic Experts
      Group (JPEG) and wavelet image compression techniques affect medical image
      content. It begins with a brief explanation of how the JPEG and wavelet
      algorithms work, and describes in general terms what effect they can have on
      image quality (removal of noise, blurring, and artifacts). It then focuses more
      specifically on medical image diagnostic content and explains why subtle
      pathologies, that may be difficult for the human eye to discern because of low
      contrast, are generally very well preserved by these compression algorithms. By
      applying a wavelet decomposition to the whole image and to specific regions of
      interest (ROI), and by understanding how the lossy quantization step attenuates
      signals in those decomposition energy subbands, much can be learned about how
      tolerant various anatomical structures are to compression. High-frequency
      anatomical structures that have their energy represented by a few large
      coefficients (in the wavelet domain) will be well preserved, while, those
      structures with high frequency energy distributed over numerous smaller
      coefficients are the most vulnerable to compression. Digitized films showing
      subtle chest nodules, a subtle stress fracture, and CT and MR images are used to
      show these results.

PMID- 9268842
TI  - READS: a radiology-oriented electronic analysis and display station.
AB  - READS is a picture archiving and communications system (PACS) display program
      that is tailored to allow a radiologist to efficiently perform image review
      tasks. In this study, the image review process was observed and functional
      patterns were identified. These were used to define a design that was considered
      to represent the optimal balance of compromises for a low-cost review station
      that also allowed easy addition of new functionality. As a result, a program was
      designed and implemented that has been found to be acceptable for image review
      and for special image processing function development.

PMID- 9268843
TI  - Automatic segmentation, tissue characterization, and rapid diagnosis enhancements
      to the computed tomographic colonography analysis workstation.
AB  - An image processing system developed to support examination of computed
      tomographic colonoscopy (CTC) was developed in 1995. The clinical viability of
      CTC is enhanced by the solution of several technical problems. These problems
      include the limited detectability of sessile polyps and difficulties in
      discrimination between polypoid masses and retained stool. CTC is also made more
      feasible by simplifying the required colon preparation and reducing the time
      required to analyze scan results. Each of these challenges have been addressed by
      enhancements to the CTC analysis workstation software. Endoluminal volume
      rendering has been enhanced by the addition of automatic segmentation to
      facilitate analysis of colon segments, which contain tagged liquid stool. By
      automating this function, the system is able to process scans that are acquired
      following a wide variety of colon preparation protocols. Similar approaches have
      been used to identify retained stool. Automatic tissue characterization has also
      been incorporated into the volume rendering routines to help identify and
      diagnose polypoid masses. These enhancements have improved the quality of CTC
      interpretation, while reducing the time required to perform the analysis. This
      time reduction was necessary to reduce the cost of CTC enough to make it viable
      for asymptotic population screening. To date, over 150 patient examinations have
      been performed using this new technique. A recent blinded, prospective study
      reporting the results from two independent observers has been presented. The
      technique is feasible, reliable, and has been implemented clinically with results
      reported within 1 hour of the examination.

PMID- 9268844
TI  - PACS/IMAC technology assessment.
AB  - According to Peter Ogle of Digital Imaging (San Francisco, CA), "Radiologists
      should help identify common values for the use of information technology in
      medicine." Achieving a set of common values often requires a framework for
      organizing the thought process involved. That is the focus of this article in
      addressing the subject of picture archiving and communication system (PACS)
      technology assessment.

PMID- 9268845
TI  - Design and implementation of World Wide Web-based tools for image management in
      computed tomography, magnetic resonance imaging, and ultrasonography.
AB  - This article describes our experience in developing and using several web-based
      tools to facilitate access to and management of images from inside and outside of
      our department. Having recently eliminated film in ultrasound, computed
      tomography (CT) and magnetic resonance imaging (MRI), a simple method was
      required to access imaging from computers already existing throughout the
      hospital. The success of the World Wide Web (WWW), the familiarity of endusers
      with web browsers, and the relative ease of developing user interfaces virtually
      dictated that such an approach be pursued in our case. The resulting web-based
      tools allow validated users to search our Digital Imaging and Communications in
      Medicine (DICOM)-compliant archive servers for specific exams; to download image
      data from a remote site; to request the retrieval of data from long-term storage;
      to view images, and to perform certain DICOM routing operations. The existing
      infrastructure of the internet has allowed us to develop a low-cost system
      capable of being used for teleradiology. Since low-level, machine-specific
      interface programming was avoided, these tools were developed rapidly and are
      easily adapted. The familiarity of browser-based interfaces has facilitated user
      acceptance, and the benefit of platform independence minimizes software
      portability concerns.

PMID- 9268846
TI  - Implementation of a filmless mini picture archiving and communication system in
      ultrasonography: experience after one year of use.
AB  - This article details our experience in developing and operating an ultrasound
      mini-picture archiving and communication system (PACS). Using software developed
      in-house, low-end Macintosh computers (Apple Computer Co. Cupertino, CA) equipped
      with framegrabbers coordinate the entry of patient demographic information, image
      acquisition, and viewing on each ultrasound scanner. After each exam, the data
      are transmitted to a central archive server where they can be accessed from
      anywhere on the network. The archive server also provides web-based access to the
      data and manages pre-fetch and other requests for data that may no longer be on
      line. Archival is fully automatic and is performed on recordable compact disk
      (CD) without compression. The system has been filmless now for over 18 months. In
      the meantime, one film processor has been eliminated and the position of one film
      clerk has been reallocated. Previously, nine ultrasound machines produced
      approximately 150 sheets of laser film per day (at 14 images per sheet). The same
      quantity of data are now archived without compression onto a single CD. Start-up
      costs were recovered within six months, and the project has been extended to
      include computed tomography (CT) and magnetic resonance imaging (MRI).

PMID- 9268847
TI  - Evaluation of radiologist performance using telemedicine services.
AB  - Observer performance of radiologists using a telemedicine service was evaluated.
      Diagnoses between the rural and consulting radiologists agreed 84% of the time.
      The main reason for disagreement was extent of lesion rather than type or
      absence/presence. Consulting times and image quality were considered adequate.

PMID- 9268848
TI  - Users' perceptions of picture archiving and communication systems and
      teleradiology.

PMID- 9268850
TI  - Expectations and solutions for HIS/RIS/PACS dataflow and workflow.

PMID- 9268851
TI  - Picture archiving and communication system-asynchronous transfer mode network in
      a midsized hospital.
AB  - This article describes the pathway to full implementation of a hospital
      information system-picture archiving and communication system-wide area network
      (HIS-PACS-WAN) in a 300-bed acute care hospital, and the linking of that system
      to two other off-site medical centers. The PACS included direct digital capture
      of computed tomography (CT), magnetic resonance (MR) imaging, nuclear medicine,
      and ultrasonography images into an Olicon archive. Plain radiographs and
      fluoroscopy images were digitized manually and archived into an Olicon system.
      The active archive included current images on each Olicon workstation and the
      juke box. Long-term archiving of the images on removable optical discs, which
      would be loaded manually by an operator every time a request for one of these
      studies appeared on the operator's monitor, also was implemented. Ability to
      store, retrieve, and display simultaneously the physician's report of each
      procedure along with the images was an ultimate goal. The WAN is to be used for
      teleradiology and teleconferencing among the three medical centers involved in
      this study as well as other off-site locations. Phase I included the design and
      installation of the local area network (LAN) in the Department of Radiology at
      Olive View-UCLA Medical Center. This included the clinics and the inpatient and
      hospital-wide fiber-optic network and its linkage to the local telephone company.
      Phase II involved linkage of the Olicon workstations to imaging equipment. This
      implementation has been delayed significantly because of inadequate needs
      assessment, absence of planning for forward-compatibility to imaging equipment,
      and incompatibilities in DICOM conformance among vendors. Every PACS project must
      include an in-depth needs analysis, which should be updated yearly because of
      rapid turnover of technology. Although this analysis should have a heavy emphasis
      on clinical needs, it must incorporate the hospital-wide needs for an integrated
      information systems network. Integration of PACS, HIS, RIS, and a
      dictation/transcription system is a complex task that requires a full-time,
      clinically oriented project officer for successful completion.

PMID- 9268849
TI  - Benefits of distributed HIS/RIS-PACS integration and a proposed architecture.
AB  - The tight integration of the Hospital Information System/Radiology Information
      System (HIS/RIS) and the Picture Archive Communication System (PACS) has become a
      priority in modern healthcare delivery systems. Traditional paper-based systems
      are being replaced by gateway style interface engines. Gateways provide a tightly
      integrated link between the HIS/RIS and the PACS, increasing productivity by
      automating many mundane clerical tasks associated with paper-based systems. A
      centralized gateway, however, represents a processing bottleneck and single point
      of failure. A self-monitoring distributed gateway architecture that replicates
      essential services increases the fault tolerance and the overall availability of
      the gateway, while providing reduced, consistent transaction times. A possible
      distributed architecture is proposed as a means to realize the advantages of a
      distributed architecture.

PMID- 9268852
TI  - Developing a radiology data base for quality assurance.
AB  - Radiology Information Systems (RIS) are designed to capture and manage the data
      associated with ordering, executing, reporting, and billing x-ray procedures. The
      HELP Hospital Information System contains a radiology subsystem that supports
      these functions. In an effort to enhance quality assurance initiatives, we have
      created a supplemental data base. This data base contains not only the data
      traditionally generated by RISs but also data from the hospital system that is
      relevant to quality assurance. One of the goals associated with this data base is
      to use techniques from the discipline of Continuous Quality Improvement (CQI) in
      the radiology department. A focus of our initial efforts has been the time
      necessary to provide x-ray reports to ordering physicians once the imaging
      examination has been performed. Efforts to manage the portion of this time
      interval caused by transcription have resulted in a substantial decrease in the
      time required for this function. A second goal of this project is to evaluate the
      quality of x-ray ordering. This objective requires a computerized record of the
      outcome of the x-ray procedure. Initial analysis of data derived from this data
      base indicates significant differences in the ordering behavior for computed
      tomography (CT) examinations among a test group of physicians. A third goal is to
      do quality assurance on x-ray reports. Experience with pilot systems has shown
      promising results using a mathematical model of report quality. We hope to
      leverage these techniques and this quality assurance data base to define a COI
      process for medical reports in general and for x-ray reports in particular.

PMID- 9268853
TI  - Auto-faxing imaging reports to referring physicians.
AB  - One of the major service issues within Medical Imaging is delivering reports
      quickly to referring physicians. As an effort to improve service, Mount Sinai
      Hospital's Department of Medical Imaging implemented Auto-Fax to distribute
      imaging reports to physicians instead of the postal service. When a report is
      transcribed and then verified by the dictating radiologist, the radiology
      information system will automatically fax the result report to the referring
      physicians if subscribed to the Auto-Fax service. If not, the report will be
      printed and mailed out manually. A transmission log is kept recording the
      requisition number, time, date, fax number, number of pages, and transmission
      status of all reports faxed. The system will try three times to fax the report.
      If unsuccessful at all attempts, the report will be printed and sent out by mail.
      Referring physicians are required to sign an agreement that the receiving parties
      are responsible to ensure transmitted reports are kept confidential. Over 150
      referring physicians have signed on for the service. Initial problems with
      missing cover pages, missing report pages, and reports not being received by
      physicians have been resolved. A recent survey of physicians receiving reports by
      Auto-Fax indicate that the service is very popular and has increased the speed
      with which transcribed report are received. Suggestions for improvement included
      faxing reports in batches, at specific times of the day, and directly to personal
      computers. Challenges reported included photocopying thermal paper faxes and
      sorting reports (for those offices with shared fax machines).

PMID- 9268854
TI  - Video networking of cardiac catheterization laboratories.
AB  - A video telecommunication network was established to transmit coronary images
      between a cardiac catheterization laboratory and a remote core laboratory. In 40
      patients during interventional procedures, cine angiograms, live fluoroscopy,
      intravascular ultrasound studies, and images of the cath lab were transmitted in
      real time over a T1 line at 768 kbits/second at 15 frames/second. RESULTS:
      Measurements of angiographic and intravascular ultrasound parameters were very
      close between the original studies and the transmitted images. The
      telecommunication link up during the interventional procedures had a significant
      affect in 58% of cases.

PMID- 9268855
TI  - Real-time telediagnosis of radiological images through an asynchronous transfer
      mode network: the ARTeMeD project.
AB  - The ARTeMeD project aims to solve problems of interactivity and real-time in
      teleradiology. It integrates personal multimedia facilities and patient data
      access in a common platform that allows radiologists to collaborate from remote
      sites through a suitable communication support. ARTeMeD is based on asynchronous
      transfer mode (ATM) network technology and an optimized manipulation of medical
      image material. The ARTeMeD system opens interesting perspectives in the area of
      collaborative teleradiology.

PMID- 9268856
TI  - Security for the digital information age of medicine: issues, applications, and
      implementation.
AB  - Privacy and integrity of medical records is expected by patients. This privacy
      and integrity is often mandated by regulations. Traditionally, the security of
      medical records has been based on physical lock and key. As the storage of
      patient record information shifts from paper to digital, we find new security
      concerns. Digital cryptographic methods provide solutions to many of these new
      concerns. In this paper we discuss the new security concerns, new legislation
      mandating secure medical records, and solutions providing this security.

PMID- 9268857
TI  - The laser film digitizer: density, contrast, and resolution.
AB  - This work evaluates differences in density linearity, contrast, and resolution of
      digital images acquired from a laser film scanner. A calibrated photographic step
      tablet tested linearity of diffuse optical density (OD). It was digitized within
      center openings of a dark and light film. The 14- x 17-inch films were scanned
      into 1024 x 1280 picture elements of 8 bits. A photographic tapered resolution
      guide evaluated the scanner's detail resolution. A single characteristic curve
      adequately represents the rate of change of OD per pixel value, but two piecewise
      linear functions are better. One ranges in light OD and a second in dark OD.
      Contrast shows a steeper slope in a light film rather than a dark film, yet a
      greater difference exists between two identical digitizers. The resolution test
      diminishes at 1.3 line pairs per mm (LP/mm), which compares to a Nyquist limit of
      1.44 LP/mm. Such density, contrast, and resolution tests yield a benchmark to
      assure quality operations.

PMID- 9268858
TI  - Advanced digital mammography.
AB  - Mammography is the most effective method for early detection of breast cancer and
      yet, 10% to 30% of women who have breast cancer and undergo mammography have
      negative mammograms. Furthermore, of the women who are sent to biopsy, only 20%
      to 40% actually have breast cancer. Quantitative analysis of the radiographic
      features of microcalcifications and masses may help radiologists improve their
      specificity.

PMID- 9268859
TI  - A method for detecting microcalcifications in digital mammograms.
AB  - Microcalcification clusters are often an important indicator for the detection of
      malignancy in mammograms. In many cases, microcalcifications are the only
      indication of a malignancy. However, the detection of microcalcifications can be
      a difficult process. They are small and can be embedded in dense tissue. This
      paper presents a method for automatically detecting microcalcifications. We
      utilize a high-boost filter to suppress background clutter enabling segmentation
      even in very dense breast tissue. We then use a threshholding and region growing
      technique to extract candidate microcalcifications. Likely microcalcifications
      are then identified by a linear classifier. We apply this method to images
      selected from the LLNL/UCSF Digital Mammogram Library, and produce a receiver
      operating characteristic (ROC) curves to detail the trade-off between probability
      of detection and false alarms. Finally, we exam the ability to properly select a
      threshold to achieve a desired probability of detection based upon a training
      set. This is a US government work. There are no restrictions on its use.

PMID- 9268860
TI  - Digital mammography and the Mammography Quality Standards Act.

PMID- 9268861
TI  - From ship to shore: "telemedicine at the deckplates" the telemedicine multimedia
      integrated distribute network (MIDN) project.

PMID- 9268862
TI  - Transferring technology from the intelligence community to the medical community.

PMID- 9268863
TI  - Experience with DICOM interfaces at the Department of Veterans Affairs.

PMID- 9268864
TI  - Implementation of a radiology electronic imaging network: the community teaching
      hospital experience.
AB  - Because of their typically small in-house computer and network staff, non
      university hospitals often hesitate to consider picture archiving and
      communication system (PACS) as a solution to the very demanding financial,
      clinical, and technological needs of today's Radiology Department. This article
      presents the experiences of the 3-year process for the design and implementation
      of the Radiology Electronic Imaging Network (REIN) in the Department of Radiology
      at The Western Pennsylvania Hospital (WPH). WPH embarked on this project in late
      1994 to find a solution to the very pressing demands to reduce operating costs
      and improve service to primary care clinicians, both on-site and at WPH
      affiliated clinics. A five-member committee consisting of in-house medical,
      administrative, information services, and medical physics staff was formed to
      design a network that would satisfy specific needs of WPH by using a phased mini
      PACS approach and to select the various vendors to implement it. Suppliers for
      individual mini-PACS were selected to provide modality-specific solutions. For
      the backbone network, vendors were evaluated based on their technological
      progress, competence and resources, the commitment of the company to the imaging
      network business, and their willingness to embark on a mid-sized PACS project
      such as this. Based on patient volume, workflow patterns, and image quality
      requirements, the committee produced proposals detailing number and location of
      workstations, short- and long-term memory requirements, and so on. Computed
      tomography/magnetic resonance imaging, computer radiography, ultrasound, nuclear
      medicine, digital fluoroscopy, and angiography mini-PACS have been implemented
      over the past 2 years, and most of these are already integrated into the main
      REIN. This article presents detailed information concerning the design, selection
      and implementation processes, including storage requirement calculations. This
      indicates that PACS implementation is achievable for community hospitals with
      small computer, networking, and physics departments. Also presented are
      recommendations concerning design and vendor selection, that may be helpful for
      similar institutions.

PMID- 9268865
TI  - MIRIAM: the PACS project in Paris: overview and implementation.
AB  - In this article the authors describe the Management Informatique de la Radiologie
      et de l'Imagerie Medicale (MIRIAM) major picture archiving and communication
      system (PACS) project in Paris, France. The Assistance Publique of Paris, France
      is a healthcare provider and took the initiative to start the largest PACS
      program in Europe to date. The MIRIAM project will start in 1997 and will be used
      in different, consecutive phases. A consortium of several companies is in charge
      of the implementation. Thirty-three hospitals with 54 imaging departments will be
      integrated in one system.

PMID- 9268866
TI  - Implementation of the Medical Information, Communication, and Archive System
      (MICAS).

PMID- 9268867
TI  - Picture archiving and communication system implementation: the practical
      considerations of adapting the technology to the real world of health care
      operations.
AB  - The issues discussed in this article are just some of the real-life
      considerations a facility's management team should address during the planning
      process as they make decisions about PACS implementation. We currently are
      working with the management teams of many facilities on PACS implementation
      projects that have yet to be completed. In the future, we hope to report on our
      experiences, including both successes and failures, as construction is completed
      and the systems actually are implemented.

PMID- 9268869
TI  - Optimizing radiology in the new picture archiving and communication system
      environment.
AB  - Picture archiving and communications systems (PACS) have inescapably altered the
      face of radiology. Images are available to radiologists and clinicians alike,
      nearly instantaneously. For patient care management, service has improved, but
      without inclusion of input from radiologists. Effecting timely report
      availability requires reorganization of radiology. In a hospital-wide PACS
      environment, we undertook to render a preliminary report on all nonprocedural
      computed radiography examinations within 30 minutes in a teaching environment.
      Two periods of time in the same month were analyzed, one before reorganization
      and one after. Of 686 reports, 117 were examined with a statistical significance
      of alpha = .05 (95% confidence) and a power of 90%. Average times for examination
      acquisition to preliminary report availability on the PACS decreased from 5 hours
      to 31 minutes. Standard deviation in report generation times decreased from 8
      hours to 30 minutes. This preliminary study suggests that business process
      reengineering can effect improvement in information flow within a teaching
      facility resulting in radiologists rejoining the patient care management team.
      Successes, pitfalls, and future requirements are discussed.

PMID- 9268868
TI  - Experience with comparative picture archiving and communication system baseline
      data collection at four Veterans Affairs Medical Centers: methodology, lessons
      learned, and suggestions for improvement.

PMID- 9268870
TI  - CD-based image archival and management on a hybrid radiology intranet.
AB  - This article describes the design and implementation of a low-cost image archival
      and management solution on a radiology network consisting of UNIX, IBM personal
      computer-compatible (IBM, Purchase, NY) and Macintosh (Apple Computer, Cupertino,
      CA) workstations. The picture archiving and communications system (PACS) is
      modular, scaleable and conforms to the Digital Imaging and Communications in
      Medicine (DICOM) 3.0 standard for image transfer, storage and retrieval. Image
      data is made available on soft-copy reporting workstations by a work-flow
      management scheme and on desktop computers through a World Wide Web (WWW)
      interface. Data archival is based on recordable compact disc (CD) technology and
      is automated. The project has allowed the radiology department to eliminate the
      use of film in magnetic resonance (MR) imaging, computed tomography (CT) and
      ultrasonography.

PMID- 9268871
TI  - Optimization of a low-cost truly preemptive multitasking PC diagnostic
      workstation.
AB  - The Windows 95/NT operating systems (Microsoft Corp, Redmond, WA) currently
      provide the only low-cost truly preemptive multitasking environment and as such
      become an attractive diagnostic workstation platform. The purpose of this project
      is to test and optimize display station graphical user interface (GUI) actions
      previously designed on the pseudomultitasking Macintosh (Apple Computer,
      Cupertino, CA) platform, and image data transmission using time slicing/ dynamic
      prioritization assignment capabilities of the new Windows platform. A diagnostic
      workstation in the clinical environment must process two categories of events:
      user interaction with the GUI through keyboard/mouse input, and transmission of
      incoming data files. These processes contend for central processing units (CPU)
      time resulting in GUI "lockout" during image transmission or delay in
      transmission until GUI "quiet time." WinSockets and the Transmission Control
      Protocol/Internet Protocal (TCP/IP) communication protocol software (Microsoft)
      are implemented using dynamic priority timeslicing to ensure that GUI delays at
      the time of Digital Imaging and Communications in Medicine (DICOM) file transfer
      do not exceed 1/10 second. Assignment of thread priority does not translate into
      an absolute fixed percentage of CPU time. Therefore, the relationship between
      dynamic priority assignment by the processor, and the GUI and communication
      application threads will be more fully investigated to optimize CPU resource
      allocation. These issues will be tested using 10 MB/sec Ethernet and 100 MB/sec
      fast and wide Ethernet transmission. Preliminary results of typical clinical
      files (10 to 30 MB) over Ethernet show no visually perceptible interruption of
      the GUI, suggesting that the new Windows PC platform may be a viable diagnostic
      workstation option.

PMID- 9268872
TI  - Effect of screen monitor number on radiologist productivity in the interpretation
      of portable chest radiographs using a picture archiving and communication system.

PMID- 9268873
TI  - Variation of monitor luminance on radiologist productivity in the interpretation
      of skeletal radiographs using a picture archiving and communication system.

PMID- 9268874
TI  - Viewport: an object-oriented approach to integrate workstation software for tile
      and stack mode display.
AB  - Diagnostic workstation design has migrated towards display presentation in one of
      two modes: tiled images or stacked images. It is our impression that the
      workstation setup or configuration in each of these two modes is rather distinct.
      We sought to establish a commonality to simplify software design, and to enable a
      single descriptor method to facilitate folder manager development of "hanging"
      protocols. All current workstation designs use a combination of "off-screen" and
      "on-screen" memory whether or not they use a dedicated display subsystem, or
      merely a video board. Most diagnostic workstations also have two or more
      monitors. Our central concept is that of a "logical" viewport that can be smaller
      than, the same size as, or larger than a single monitor. Each port "views" an
      image data sequence loaded into offscreen memory. Each viewport can display one
      or more images in sequence in a one-on-one or traditionally tiled presentation.
      Viewports can be assigned to the available monitor "real estate" in any manner
      that fits. For example, a single sequence computed tomography (CT) study could be
      displayed across all monitors in a tiled appearance by assigning a single large
      viewport to the monitors. At the other extreme, a multisequence magnetic
      resonance (MR) study could be compared with a similar previous study by assigning
      four viewports to each monitor, single image display per viewport, and assigning
      four of the sequences of the current study to the left monitor viewports, and
      four of the earlier study to the right monitor viewports. Ergonomic controls
      activate scrolling through the off-screen image sequence data. Workstation folder
      manager hanging protocols could then specify viewports, number of images per
      viewport, and the automatic assignment of appropriately named sequences of
      current and previous studies to the viewports on a radiologist-specific basis.
      Furthermore, software development is simplified by common base objects and
      methods of the tile and stack modes. Prototype workstation display software and
      folder manager protocol implementation will be described and demonstrated.

PMID- 9268875
TI  - User interface configurability in the physician workstation key to optimized
      enterprise-wide image presentation and analysis.

PMID- 9268876
TI  - Use of image processing presets in chest radiography.

PMID- 9268877
TI  - Comparison between conventional radiography and Thoravision in the study of the
      normal chest.

PMID- 9268878
TI  - Unsharp masking technique using multiresolution analysis for computed radiography
      image enhancement.
AB  - An unsharp masking technique (USM) is one of the image processing methods used in
      the computed radiography (CR) system. To further promote the performance of the
      USM, we developed the NEW-USM processing that can control the frequency
      enhancement characteristics flexibly and accommodate an extensive range of
      diagnostic targets. The NEW-USM and USM were performed on femur images acquired
      by computed radiography (model FCR9000; Fuji Medical Systems USA Inc, Stamford,
      CT), and the resulting images were compared. In the NEW-USM image, bone
      structures are enhanced as sharply as in the USM image, whereas the surrounding
      soft tissue structures, such as muscle are enhanced more strongly than in the USM
      image. Furthermore, the absence of the bone structure that may suggest
      pathological change is more obvious in the NEW-USM image. The newly developed NEW
      USM can appropriately enhance diagnostic information over the whole range of
      image frequencies, thereby expanding utility of the USM.

PMID- 9268879
TI  - Implementation of an electronic teaching file using web technology.
AB  - The implementation of an electronic teaching file using web technology is
      discussed in this article. A web client server model is used for a standard web
      browser capable of displaying joint photographic Experts Group (JPEG) compression
      images. Like other web-based teaching files, this teaching file in a similar way
      uses a database containing information. This database section of the teaching
      file allows flexible database querying and viewing of pages generated by
      hypertext markup language (HTML). Because the browser client is so flexible,
      images types such as video and 3D representations with virtual reality markup
      language (VRML) can be displayed.

PMID- 9268880
TI  - Publishing radiology educational material on the Internet: analysis of e-mail
      responses.

PMID- 9268881
TI  - A typology of simulators for medical education.
AB  - The growth of simulation technology has brought about rapid innovation in medical
      education systems. The task of developing and programming these systems is
      complex. To simplify the process, we developed a typology of medical simulators
      which allows critical elements to be identified and characterized. The analysis
      identifies the patients, the procedure, the physician, and the professor as
      essential elements in any medical education simulator. The level of interactivity
      of these elements determines the "realism" of the simulator. The development of a
      fully interactive simulator for ultrasound education will be presented.

PMID- 9268882
TI  - Quasi-3D kinematic modeling and parametric image processing of a multiframe ECG
      gated planar 99mTc-SestaMIBI myocardial perfusion scintigraphic study.

PMID- 9268883
TI  - Comparison of image processing techniques (magnetic resonance imaging, computed
      tomography scan and ultrasound) for 3D modeling and analysis of the human bones.
AB  - Magnetic resonance imaging (MRI), computed tomography scanning (CT scan), and
      ultrasound imaging techniques (UI) were used for data acquisition to
      construct/develop a 3D solid model of the human tibia, femur, and skull. CT scan
      was found to be an acceptable technique for cadavers. CT scans are harmful to the
      human body in large doses, while MRIs and ultrasound are known to be safe.
      However, MRIs form a better tool in performing this image generation task for
      living beings because of its high resolution capacity when compared with images
      obtained using ultrasound techniques. High resolution poses to be a very
      important factor, as the consideration of various material properties of the
      bones was part of the emphasis of this research. MRIs have the capacity of
      displaying a distinct boundary between the muscles and the bone, in addition to
      the boundary between the cortical and the cancellous region within the bone.
      Ultrasound was found to be the cheapest technique and gave reasonably good
      results for just the outside boundaries of the bone. The models of the human
      bones were generated on a Computer Aided Design (CAD) system. The cross-sections
      obtained from (MRI, CT, or UI) were scanned into the computer. Image processing
      software was used to detect the boundaries of the bones. A C + + program was used
      to read the coordinates of the edges and construct a B-spline curve on the CAD
      system. The curves were converted to a B-rep solid using skinning. The solid
      models were meshed, constrained, and material properties were assigned to
      different regions of the models for Finite Element Analysis (FEM).

PMID- 9268884
TI  - A method for rapid computation of maximum intensity projection images.
AB  - We describe a method for rapid calculation of maximum intensity projection (MIP)
      images. The method is applied to 10 example cases with more extensive testing in
      1 case. Measurements of calculation time for all 10 cases show good performance
      (less than 1.2 seconds) for calculating a MIP image that is a very faithful
      representation of the original (less than 2% of pixels differ from original
      image). We also demonstrate that the computation time is related linearly to the
      number of pixels used, allowing arbitrarily rapid computation rates. This
      technique may be helpful as a navigation aid in evaluation magnetic resonance
      (MR) angiography data.

PMID- 9268885
TI  - Radiology teaching file cases on the World Wide Web.
AB  - The presentation of a radiographic teaching file on the World Wide Web can be
      enhanced by attending to principles of web design. Chief among these are
      appropriate control of page layout, minimization of the time required to download
      a page from the remote server, and provision for navigation within and among the
      web pages that constitute the site. Page layout is easily accomplished by the use
      of tables; column widths can be fixed to maintain an acceptable line length for
      text. Downloading time is minimized by rigorous editing and by optimal
      compression of image files; beyond this, techniques like preloading of images and
      specification of image width and height are also helpful. Navigation controls
      should be clear, consistent, and readily available.

PMID- 9268886
TI  - A general technique for automatic left ventricle boundary validation: relation
      between gray scale cardioangiograms and observed boundary errors.
AB  - This article presents an automatic left ventricle boundary validation technique
      using the gray scale cardioangiograms, the observed boundary errors, and the left
      ventricle boundaries from any source that needs to be validated. This validation
      technique is based on the gray scale information near the boundary of the left
      ventricle in the cardioangiograms. Using a mutually exclusive window of fixed
      size, which is centered on the left ventricle boundary vertex and along the left
      ventricle contour, we compute a difference in contrast value for areas of the
      window both inside and outside the left ventricle region. These contrast values
      then are regressed against the observed boundary errors. The observed boundary
      errors are computed using the polyline distance measure, by comparing two sets of
      boundaries: boundaries estimated from any boundary estimation algorithm, and the
      original ground truth boundaries as traced by the cardiologist. We performed our
      experiments on a database of 245 patient studies, each having two frames: end
      diastole (ED) and end-systole (ES). The mean boundary error before running the
      validation system was 4.4 mm. Using our boundary validation system, by rejecting
      5% to 10% of the patient studies, the validation system results in an error of
      4.0 mm for the cross-validation case and 3.85 mm for the ideal case. We show the
      reliability curves of our validation system by computing the probability of false
      alarm, probability of mis-detection, and mean predicted errors when a total of n
      patients are rejected from the database of 245 studies.

PMID- 9268887
TI  - Image processing assessment of femoral osteopenia.
AB  - Visual assessment of femoral osteopenia (the radiographic presentation of
      osteoporosis) is unreliable. Many of the short-comings of observer grading can be
      overcome by digital image analysis. Our group has developed algorithms to make
      automatic assessment of osteopenia from clinical radiographs. Texture Analysis
      Models (TA) commonly used in image analysis were investigated as measures of
      osteopenia. Unlike densitometric methods, TA characterizes properties of the
      structure of the image (ie, trabecular patterns). A group of women were analyzed
      whose subjects ranged from those at risk of osteoporosis (n = 24) to normal (n =
      40). Using an IBM PC, frame-grabber, camera, and light-box, we appraised five
      statistical TA algorithms for assessment of the femoral neck in standard pelvic
      radiographs: (1) Fractal Signature (FS) describes the image's fractal nature. (2)
      Auto-Correlation of unaltered and Sobel Edge Transformed images (ACSE) measures
      image spatial self-similarity. (3) Co-occurrence Matrices (CM) gives the joint
      probability of greylevels with distance/direction and describes statistical
      relationships of image variation. (4) Textural Spectrum (TS) neighborhood pixel
      relationships measure regional directional and pixel-inversion properties. (5)
      Eular Numbers (EN) describe texture by properties (such as connectivity) of
      binary images. Good reproducibility from repeated analysis of radiographs was
      shown using both paired t-tests and Altman-Bland's methods. We have shown a
      correlation between femoral neck bone mineral density (BMD-the "gold standard" of
      osteoporosis assessment) and textural measures for all five algorithms.
      Significant measures of osteopenia were: ACSE (r = 0.6, P < .001), CM (r = -0.69,
      P < .001), FS (r = 0.35, P < .01), TS (r = 0.52, P < .001) and EN (r = -0.39, P <
      .01). Relationships were also found between textural characteristics and
      age/weight. TA techniques characterize the radiographic changes of bone in
      osteoporosis. Technology based on these ideas may have a place alongside BMD
      measurements in the assessment of this condition.

PMID- 9268888
TI  - Mass detection in single-view mammograms.

PMID- 9268889
TI  - Skinline detection in digitized mammograms.

PMID- 9268890
TI  - Iconic reporting of scintigraphic findings: five years experience in our routine
      reporting.

PMID- 9268891
TI  - Sectional anatomy using the personal computer.

PMID- 9268892
TI  - Project MICAS--medical information, communication and archive system: PACS
      implementation at the University of Rochester Medical Center.

PMID- 9268893
TI  - New software toolkits for comprehensive visualization and analysis of three
      dimensional multimodal biomedical images.

PMID- 9268894
TI  - An Internet-connected, patient-specific, deformable brain atlas integrated into a
      surgical navigation system.

PMID- 9268895
TI  - Obstructive sleep apnoea syndrome: results and conclusions of a principal
      component analysis.
AB  - A cephalometric analysis according to Hasund, supplemented by special obstructive
      sleep apnoea syndrome (OSAS) parameters, was performed on 169 patients who had
      been referred from the sleep laboratory. Statistical analysis showed a
      correlation between specific cephalometric landmarks including posterior airway
      space (PAS), a soft palate length, hyoid position and posterior growth
      development of the mandible and OSAS severity. A principal component analysis
      differentiated between four subgroups of OSAS patients: (1) orthognathic obese
      subjects; (2) patients with a long soft palate and low-positioned hyoid; (3)
      retrognathic patients with narrow PAS; and (4) prognathic ones. Lateral
      cephalometry is an important contribution to OSAS diagnostics and oral and
      maxillofacial therapy procedures.

PMID- 9268896
TI  - Maxillary advancement by distraction osteogenesis using osseointegrated implants.
AB  - The purpose of this study was to establish a new technique for distraction
      osteogenesis in the maxilla, using an osseointegrated implant and intraoral
      device. After extraction of the premolar and molar teeth, four titanium implants
      were installed in the maxillary alveolar bone. Three months later, the
      distraction device was connected to the abutments, and osteotomy in the medial
      portion of maxilla between the implants was performed. Distraction was carried
      out at the rate of 1 mm per day to obtain a 10-mm elongation, Morphological,
      radiographic and histological examinations showed that successful maxillary
      advancement was achieved. New bone was primarily formed by intramembranous
      ossification and partial endochondral ossification. Titanium implants placed for
      anchorage of the distraction device remained stable during the course of
      maxillary advancement. This technique can provide significant advancement of the
      maxilla with better stability. The treatment system can be applied in any kind of
      maxillary deformities which need to be corrected surgically by classic osteotomy
      without bone grafting.

PMID- 9268897
TI  - Inherent precision of mechanical, infrared and laser-guided navigation systems
      for computer-assisted surgery.
AB  - This investigation detects the inherent precision of four navigation systems, of
      different structural type, for computer-assisted surgery, ranging from 0.1 to 1.8
      mm: the Viewing Wand with a mechanical arm, and three new systems, the SMN
      microscope and STP pointer with infrared technology and the MKM system with laser
      autofocus. For this purpose, a new standard to detect separately the inherent
      deviations of navigation systems from the deviations caused by acquisition of CT
      data sets, is introduced. The measurements are performed within a complete three
      dimensional room, consisting of three orthogonal planes of a geometric model. The
      method introduced is valid for regular measurements of the inherent precision of
      navigation systems for quality assurance in order to prevent intraoperative
      failure caused by insufficient potentiometers, infrared transmitters or
      receivers.

PMID- 9268898
TI  - Computer-aided navigation in secondary reconstruction of post-traumatic
      deformities of the zygoma.
AB  - Augmented reality technology was used in 5 patients for secondary reconstruction
      of post-traumatic unilateral deformities of the zygomaticomaxillary complex.
      Three electromagnetic sensors interfaced to a computer-aided navigation system
      (ARTMA Biomedical Inc.) were utilized. The computer navigation procedure was
      planned by drawing graphic lines on the CT scan at the level of the zygomatic
      arch, representing the outer surface of the zygoma. The desired position of the
      displaced zygoma was planned by mirroring from the healthy side, using a virtual
      mid-sagittal plane. These virtual graphics were presented intraoperatively on a
      TV monitor and also on the surgeon's see-through head-mounted display. Correct
      reduction was assumed when the virtual line representing the position of the
      zygoma before the osteotomy reached the virtual line defined preoperatively as
      the desired position. The advantages of the technique presented are that a
      complete exposure of the zygomatic bone is no longer necessary, and coronal and
      subciliary incisions may be avoided unless enophthalmos correction has to be
      carried out, which was in fact necessary in 2 patients. The results of zygomatic
      reconstruction have been satisfactory in all 5 patients.

PMID- 9268899
TI  - Histological findings in the alveolar sockets and tooth roots after experimental
      mandibular fractures in dogs.

PMID- 9268900
TI  - Tooth eruption through autogenous and xenogenous bone transplants: a histological
      and radiographic evaluation in beagle dogs.
AB  - The effect of implanting autogenous and xenogenous (Bio-Oss) bone transplants
      into metabolically active sites within beagle dog mandibles during permanent
      premolar tooth eruption was examined. Ten 14-week-old beagles were used. Before
      commencing the radiographic experiments, metal bone markers were placed in the
      caudal margin of the mandible at the age of 10 weeks. The deciduous first and
      third molar teeth were extracted and their sockets over the permanent second and
      fourth premolars were implanted with autogenous particulate enchondral iliac
      crest bone, autogenous particulate membraneous mandibular body bone, xenogenous
      bovine anorganic bone mineral spongiosa granules (1-2mm3) (Bio-Oss, Geistlich
      Pharma, Switzerland) of left empty. The third premolar served as control site.
      Standardized oblique lateral radiographs were taken once a week. A number of
      coordinates of defined points and structures were determined by means of a
      coordinate digitizing system. Animals were killed 4, 10 and 16 weeks after bone
      transplantation for histological examination of the transplantation sites. All
      premolars showed no delay in eruption or disruption of crown and root
      development. On histology, the Bio-Oss particles were not resorbed or integrated
      in the alveolar bone but were pushed forward into the gingiva. We have
      demonstrated that there is on difference in the eruption curve of the permanent
      premolars in the four groups (ANOVA P > 0.5) and that bone transplantation has no
      inhibitory effect on eruption (ANOVA P > 0.3) and crown development of the
      underlying permanent premolar but that Bio-Oss does not have the same resorbable
      or integrating capability as autogenous bone grafts.

PMID- 9268901
TI  - Reconstruction and rehabilitation of short-range, high-velocity gunshot injury to
      the lower face: a case report.
AB  - War injuries can range from the most minor to the devastating and life
      threatening. Multidisciplinary care is required for successful management of
      survivors. In the acute phase, care may involve emergency surgeons,
      anaesthetists, neurosurgeons, ophthalmic surgeons, vascular surgeons and ENT
      specialists in addition to the oral and maxillofacial surgeon. Afterwards,
      definitive treatment of facial hard and soft tissue gunshot injuries depends
      ultimately on the abilities and skills of the oral and maxillofacial surgeon and
      his appreciation of such injuries. The timing and sequence of the surgical
      procedures used for reconstruction and rehabilitation of maxillofacial gunshot
      injuries are crucial to a successful outcome and aesthetic result. If incorrect,
      they may lead indefinitely to infection, graft rejection, wound dehiscence with
      consequent multiple revisional operations and complications which will prolong
      hospital stay, and increase treatment costs and morbidity in these patients. In
      this article, we describe the treatment protocol for reconstruction and
      rehabilitation of a typical case of devastating gunshot injury to the lower face
      and propose a staged sequence of surgical treatment based on an 8-year experience
      gained in treating war casualties during the Iraq-Iran war (1980-1988).

PMID- 9268902
TI  - Large arteriovenous high-flow mandibular, malformation with exsanguinating dental
      socket haemorrhage: a case report.
AB  - Arteriovenous malformations (AVMs) of the jaws are extremely rare lesions, which
      are probably hamartomas of developmental malformations. In this article we
      present an extremely high-flow AVM of the lower jaw with exsanguinating bleeding
      from the socket of the exfoliated tooth. Repeated episodic bleedings were
      controlled with local pressure and packing. Digital subtraction angiography
      revealed a high-flow, high-shunt AVM. Preoperative embolization and external
      carotid artery ligation, dental extraction, curettage and packing with Gelfoam
      were done. Postoperative bleeding stopped, bruit ceased, and it had disappeared
      completely after 6 months follow-up. On the second follow-up visit, 3 months
      later, the patient was found to have no problems.

PMID- 9268903
TI  - Evaluation of irreversible compression of digitized posterior-anterior chest
      radiographs.
AB  - The purpose of this article is to assess lossy image compression of digitized
      chest radiographs using radiologist assessment of anatomic structures and
      numerical measurements of image accuracy. Forty posterior-anterior (PA) chest
      radiographs were digitized and compressed using an irreversible wavelet technique
      at 10, 20, 40, and 80:1. These were presented in a blinded fashion with an
      uncompressed image for A-B comparison of 11 anatomic structures as well as
      overall quality assessments. Mean error, root-mean square (RMS) error, maximum
      pixel error, and number of pixels within 1% of original value were also computed
      for compression ratios from ratios from 5:1 to 80:1. We found that at low
      compression (10:1) there was a slight preference for compressed images. There was
      no significant difference at 20:1 and 40:1. There was a slight preference on some
      structures for the original compared with 80:1 compressed images. Numerical
      measures showed high image faithfulness, both in terms of number of pixels that
      were within 1% of their original value, and by the average error for all pixels.
      Our findings suggest that lossy compression at 40:1 or more can be used without
      perceptible loss in the representation of anatomic structures. On this finding,
      we will do a receiver-operator characteristic (ROC) analysis of nodule detection
      in lossy compressed images using 40:1 compression.

PMID- 9268904
TI  - Forced choice and ordinal discrete rating assessment of image quality: a
      comparison.
AB  - This study compared a five-category ordinal scale and a two-alternative forced
      choice subjective rating of image quality preferences in a multiabnormality
      environment. 140 pairs of laser-printed posteroanterior (PA) chest images were
      evaluated twice by three radiologists who were asked to select during a side-by
      side review which image in each pair was the "better" one for the determination
      of the presence or absence of specific abnormalities. Each pair included one
      image (the digitized film at 100 microns pixel resolution and laser printed onto
      film) and a highly compressed (approximately 60:1) and decompressed version of
      the digitized film that was laser printed onto film. Ratings were performed once
      with a five-category ordinal scale and once with a two-alternative forced-choice
      scale. The selection process was significantly affected by the rating scale used.
      The "comparable" or "equivalent for diagnosis "category was used in 88.5% of the
      ratings with the ordinal scale. When using the two-alternative forced-choice
      approach, noncompressed images were selected 66.8% of the time as being the
      "better" images. This resulted in a significantly lower ability to detect small
      differences in perceived image quality between the noncompressed and compressed
      images when the ordinal rating scale is used. Observer behavior can be affected
      by the type of question asked and the rating scale used. Observers are highly
      sensitive to small differences in image presentation during a side-by-side
      review.

PMID- 9268905
TI  - Classification of normal and abnormal lungs with interstitial diseases by rule
      based method and artificial neural networks.
AB  - We devised an automated classification scheme by using the rule-based method plus
      artificial neural networks (ANN) for distinction between normal and abnormal
      lungs with interstitial disease in digital chest radiographs. Four measures used
      in the classification scheme are determined from the texture and geometric
      pattern feature analyses. The rms variation and the first moment of the power
      spectrum of lung patterns are determined as measures for the texture analysis. In
      addition, the total area of nodular opacities and the total length of linear
      opacities are determined as measures for the geometric-pattern feature analysis.
      In our classification scheme with these measures, we identify obviously normal
      and abnormal cases first by the rule-based method and then ANN is applied for the
      remaining difficult cases. The rule-based plus ANN method provided a sensitivity
      of 0.926 at the specificity of 0.900, which was considerably improved compared to
      performance of either the rule-based method alone or ANNs alone.

PMID- 9268906
TI  - A simple image display application for windows.
AB  - The purpose of this project was to develop a simple application for displaying
      low-to-moderate resolution digital images under the Windows operating
      environment. The display of scintigraphic images was of special interest, and for
      this reason the program was designed to show sequences of images and to account
      for broad ranges of pixel values. In order to function under a variety of Windows
      versions, the program was developed using the 16-bit Microsoft C +2 compiler and
      targeted for Windows 3.1 enhanced. It was tested with Trionix images for nuclear
      medicine and Siemens for computed tomography (CT) and magnetic resonance (MR).
      The resulting application, called SID, successfully read Magnetom, Somatom,
      Trionix, and Interfile images of dimension 512 or less on Intel-based Windows PCs
      with 256 color SVGA-compatible (Super Video Graphics Adapters) video hardware.
      Early applications of the program included remote monitoring of image studies,
      resident review of teaching cases, review of research images, and preparation of
      educational materials. This article describes the features, operation, and
      potential applications of SID.

PMID- 9268907
TI  - A digital imaging and communications in medicine (DICOM) print service for chest
      imaging.
AB  - Large-scale picture archiving and communication systems (PACS) have not been
      widely implemented in this or other countries. In almost all radiology
      departments film remains the medium for diagnostic interpretation and image
      archive. Chest imaging is the dominant screening examination performed within
      most imaging departments and as such, is an extremely high-volume, low-margin
      examination. Digital technologies are being applied to chest imaging to overcome
      limitations of screen-film receptors (limited latitude) and current film
      management systems (single-image copy). Efficient management of images and
      information is essential to the success of a chest imaging program. In this
      article we report on a digital imaging and communications in medicine (DICOM)
      based centralized printing network for chest imaging. The system components and
      their operational characteristics are described. Our experience integrating DICOM
      compliant equipment supplied by several vendors is described. We conclude that
      the print model supported by DICOM is adequate for cross-sectional (eg, computed
      tomography and magnetic resonance) imaging but is too simplistic to be generally
      applied to projection radiography.

PMID- 9268908
TI  - Support line and tube visibility in chest examinations using computed
      radiography.
AB  - The visibility of support lines and tubes was compared in computed radiography
      (CR) and screen-film adult chest radiographs. Parameters investigated were
      radiation dose, image minification, and the use of unsharp mask enhancement. Five
      radiologists rated the visibility of support lines and tubes on a five-point
      scale ranging from 1 (entire course of line visible) to 5 (line not visible or
      only small portion seen). These CR results were compared with the visibility of
      support lines and tubes as assessed by the same readers for conventional screen
      film radiographs (600 speed). Support line and tube visibility improved with
      image enhancement, image minification, and increasing radiation dose. At the same
      radiation exposure, support line and tube visibility of the screen-film
      combination was superior to that of standard CR images. Application of an unsharp
      mask enhancement algorithm to CR images, however, significantly improved support
      line and tube visibility in comparison to that obtained with the screen-film
      combination. It was concluded that unsharp mask processing is a valuable tool for
      improving the visibility of support lines and tubes in CR chest radiographs.

PMID- 9268909
TI  - Computed radiography excretory urography: can the system sensitivity value be
      used as an image quality indicator?
AB  - The purpose of this study is to determine whether the computed radiography system
      sensitivity value can be used as an image quality indicator for computed
      radiography excretory urography with radiation dose reduction. One hundred and
      twenty-four patients with gynecological malignancies were studied prospectively.
      Five-minute and 10-minute computed radiographic images of excretory urography
      were obtained in each patient with different radiation doses (ie, a standard dose
      image required with screen-film method and a reduced dose one). The images were
      subjectivity scored by three radiologists without knowledge of the exposure
      factors or the system sensitivity values. The quality scores of the reduced-dose
      images used in the five steps were compared with those of the standard dose
      images (the system sensitivity value was 80 to 120). The images with reduced
      exposures were arbitrarily divided into five steps according to the system
      sensitivity value (ie, 150 to 250, 260-400, 410-600, 610-1000, and 1010-1500).
      There was a gradual degradation of the image quality as the system sensitivity
      value was increased. In terms of visualization of the bones, the images taken
      with the system sensitivity values of 150-250 (40%-67% of the standard dose
      system) showed no statistically significant difference from the standard dose
      images. As for visualization of the renal pelvic margins, the images taken with
      the system sensitivity values of 260 to 400 (2%-38% of the standard dose system)
      showed no statistically significant difference. We conclude that system
      sensitivity value can be used as a practical though approximate indicator of the
      image quality.

PMID- 9268910
TI  - Some aspects of the history of rehabilitation of the hand.

PMID- 9268911
TI  - Dynamic extension assist splinting of acute central slip lacerations.
AB  - The management of zone III extensor tendon injuries remains a challenging
      clinical problem for both the surgeon and therapist. Current treatment protocols
      include prolonged immobilization, controlled mobilization, or limited early
      dynamic splinting, but overall results are often less than optimal. This
      retrospective study describes an alternative treatment approach for acute central
      slip lacerations consisting of initial immobilization of the PIP joint in
      absolute 0 degrees extension for an average of 3.5 weeks followed by active
      flexion of the PIP joint in a finger-based dynamic extension assist splint.
      Therapy averaged approximately one visit weekly, and follow-up averaged 3.8
      months. Mean PIP joint extension was + 1 degrees, and mean PIP joint flexion was
      109 degrees. Mean DIP joint extension was -1 degree and mean DIP flexion was 67
      degrees. Mean total active motion measured in composite fashion for the PIP and
      DIP joints was 175 degrees. This treatment approach produced excellent results,
      required infrequent therapy, and utilized only finger-based splinting.

PMID- 9268912
TI  - A preliminary investigation of the neoprene tube finger extension splint.
AB  - Neoprene tube finger extension splints were analyzed to determine the production,
      amounts, and directions of force magnitude on the proximal interphalangeal joint
      during the flexing of the tube up to angles of 80 degrees. The tubes were
      examined in their empty form, with a human digit inserted into the tube, and with
      portions of the tube on the volar and dorsal surfaces removed. Upward forces
      ranged from less than 100 g to 225 g in the empty tubes. Upon insertion of a
      human digit into the tubes, forces increased from 125 g at 10 degrees to 650 g at
      80 degrees flexion. Removal of a 2-cm square portion on the dorsal surface over
      the PIP joint did not significantly affect the tube's ability to lift upward
      demonstrating little or no downward pressure in the device. The tube had little
      or no upward force following removal of a 2-cm square encompassing the angle of
      the device on the volar surface. Positive effectiveness of the tubes were
      examined in case reports.

PMID- 9268913
TI  - A profile of patients with adhesive capsulitis.
AB  - The purpose of this descriptive study is to develop a profile of patients with
      adhesive capsulitis and to describe the patients' perceived clinical progression.
      A total of 32 patients diagnosed with adhesive capsulitis and 31 control subject
      completed anonymous questionnaires designed to elicit demographic data as well as
      medical information. The adhesive capsulitis and control samples were selected
      from the same facilities in an effort to reduce bias. Data comparing the adhesive
      capsulitis group with the control group was analyzed using the Odds Ratio and
      Taylor Series Confidence Interval for Odds Ratio. Twenty-seven patients (84.4%)
      diagnosed with adhesive capsulitis fell within the age range of 40-59 years.
      Diabetes and heart disease appeared to be more prevalent in patients diagnosed
      with adhesive capsulitis as compared with the control group and general
      population. The majority of patients with adhesive capsulitis (90.6%) reported a
      perceived clinical progression that started with a pattern of pain followed by
      loss of motion. Age and concomitant medical conditions appeared to be most
      correlated with the occurrence of adhesive capsulitis. Possible reasons for the
      prevalence of diabetes and heart disease in adhesive capsulitis patients are
      discussed.

PMID- 9268914
TI  - Grip force reduction in patients with tennis elbow: influence of elbow position.
AB  - Grip force was measured in 55 consecutive patients with chronic tennis elbow.
      Grip force was markedly reduced at the pathological side, but there was also a
      striking reduction of the grip force at the pathological side when the grip force
      was measured with a straight elbow, compared with the standard position of 90
      degrees flexion. This reduction was highly significant at the pathological side
      but not at the normal control side.

PMID- 9268915
TI  - Case study of a five-stage sensory reeducation program.
AB  - The purpose of this paper is to describe a sensory reeducation program classified
      into five stages: (1) feature detection and recognition of objects; (2)
      correction of the pattern of prehension in the hand; (3) control of precise force
      for grasping objects; (4) maintenance of grip force during movement of the
      proximal joints; and (5) manipulation of objects. The program is specific to hand
      function in activities of daily living and is based on recent neurophysiological
      findings. It is illustrated by a detailed case study. The authors report that,
      through sensory reeducation a patient who had an insensitive hand gained the
      ability to recognize objects. She learned to utilize a sense of muscle resistance
      and a sense of vibration in the shoulder. Her body image improved along with the
      usefulness of her hand in activities of daily living.

PMID- 9268916
TI  - Dynamic extension splint: Rotterdam design.

PMID- 9268917
TI  - Biotin administration improves the impaired glucose tolerance of streptozotocin
      induced diabetic Wistar rats.
AB  - The effect of biotin administration on the glucose tolerance of streptozotocin
      (STZ)-induced diabetic Wistar rats was investigated. STZ-induced diabetes was
      induced by intraperitoneal injection of streptozotocin (45 mg/kg body weight as a
      single dose). The impaired glucose tolerance in response to an oral glucose load
      (1.8g per kg body weight) in STZ-induced diabetic rats (STZ-rat) was partially
      improved by intraperitoneal administration of biotin for 15 days (100
      micrograms/rat/day). However, a recovery in the STZ-rat's insulin secretion was
      not found after biotin administration. To help clarify the mechanism underlying
      the improvement in glucose tolerance seen with biotin treatment, glucokinase and
      hexokinase activities were determined in the liver and pancreas. In STZ-rats that
      had received biotin (STZ-biotin rats), glucokinase activity was higher by 3.4
      fold in liver and by 2.4-fold in pancreas than in the STZ-rats. The biotin level
      of STZ-rats was significantly lower in the liver and pancreas than that of the
      control rats (no STZ administration); but in STZ-biotin rats, the level in these
      organs recovered to the control level. These results demonstrate that injected
      biotin can improve glucose handling without increasing insulin secretion in STZ
      rats.

PMID- 9268918
TI  - Vitamin A and carotenoids stimulate differentiation of mouse osteoblastic cells.
AB  - The action of retinol and carotenoids on bone cells was investigation in vitro by
      evaluating cell growth, alkaline phosphatase activity and the mRNA expression of
      a differentiation marker protein of osteoblastic cells. The clonal osteogenic
      cell line MC3T3-E1, established from newborn mouse calvaria, has a capacity of
      differentiation into osteoblast and mineralization in vitro. Retinol and beta
      carotene inhibited the proliferation of MC3T3-E1 cells as well as DNA synthesis
      of the cells in a dose-dependent manner. Retinol induced differentiation of the
      MC3T3-E1 cells, by increasing alkaline phosphatase activity dose dependently, in
      a range from 1 to 100nm. Beta-carotene increased alkaline phosphatase activity is
      a dose-related manner in a range from 0.1 to 5 microM. Osteopontin is one of the
      matrix proteins which osteoblasts produce. Retinol increased the expression of
      osteopontin mRNA in a range from 1 to 100 nm. Beta-carotene also increased
      osteopontin mRNA expression, reaching a plateau at 1 microM. The induction of
      differentiation of MC3T3-E11 cells by beta-carotene was dose-dependent but was
      two orders of magnitude less active than that produced by retinoids. Within the
      MC3T3-E1 cells, part of the beta-carotene was effectively converted into retinol.
      Alpha-carotene, canthaxanthin and lycopene also inhibited cell proliferation at 1
      microM and increased alkaline phosphatase activity and osteopontin mRNA
      expression, but less potently so than beta-carotene. Retinol and carotenoids were
      concluded to have a direct stimulatory effect on the differentiation of
      osteoblasts at the physiological concentration.

PMID- 9268919
TI  - Effect of high concentration of ascorbate on catalase activity in cultured cells
      and tissues of guinea pigs.
AB  - This study showed that the inhibition of cell growth in 3T6, induced by the
      supplementation of ascorbate at 0.5 mM in cultured medium, was prevented by the
      addition of catalase in the range of 25-750 units/mL regardless of the degree of
      activity. However, cytotoxicity induced by concentrations of more than 2 mM
      ascorbate could not be prevented even when a high level of catalase (5,000
      units/mL) was added to the medium. Catalase activity in medium supplemented with
      ascorbate decreased with incubation time; the higher the concentration of
      ascorbate, the greater the decrease in catalase activity. These results indicate
      that even though catalase is present at a high concentration in the medium, it
      cannot prevent cytotoxicity by a high concentration of ascorbate because the
      oxygen radical derived from ascorbate inhibits its activity. We therefore
      investigated whether the inhibition of catalase activity by ascorbate could be
      observed in animal tissues. The catalase activity in the tissues of guinea pigs
      6h after the administration of ascorbate was lower than that in non-administered
      animals. When guinea pigs were fed diets containing 5 mg or 100 mg
      ascorbate/animal over a 90 weeks period, a clear affect on catalase activity in
      the high-dose ascorbate group as compared to that in the low-dose ascorbate group
      was not observed.

PMID- 9268920
TI  - Effect of arachidonate on lipid metabolism in ethanol-treated rats fed with lard.
AB  - Two groups of rats, ethanol-treated and sucrose-administered control rats, were
      fed diets with different AA content (0, 2 and 3% weight) for 14 days. Ethanol was
      administered by gavage at a single daily dose of 3 g/kg body weight. The ethanol
      treated rats showed significantly higher levels (p < 0.01) of serum ALT activity.
      The dietary AA supplement lowered the serum ALT activity and liver triglyceride
      both in control and ethanol-treated rats. Significantly lower levels of 20:4n - 6
      and 20:4n - 6/18:2n - 6 ratio and higher levels of 18:1n - 9 in both the serum
      and liver triglyceride were observed in the ethanol-treated rats. The AA
      supplemented diet induced a marked increase of 20:4n - 6 and subsequent
      significant decrease of 18:2n - 6 both in the liver and serum phospholipid in
      control and ethanol-treated rats. 18:1n - 9 in the serum and liver triglyceride
      in both groups was also markedly decreased by AA supplement. No significant
      difference was observed in the liver 6-keto-PGF(1 alpha) level between the
      ethanol-treated and control rats. In the ethanol-treated rats, the level of 6
      keto-PGF(1 alpha) was elevated in the rats fed the 3% AA-supplemented diet.
      Though the liver leukotriene B4 levels were increased by ethanol administration
      in all rats, these levels were not increased by dietary AA.

PMID- 9268921
TI  - Cosinor analysis of feed intake cycle of rats fed a zinc-deficient diet and the
      effect of zinc supplementation.
AB  - Rats fed a Zn-deficient diet develop a characteristic cyclic variation in feed
      intake (Mills et al., Am J Clin Nutr 22: 1240-1249 (1969). A preliminary analysis
      (Tamaki et al., Br J Nutr 73: 711-722 (1995)) of the cyclic variations was
      followed with a personal computer. Cosinor analysis revealed that the cyclic
      period of the feed intake of male rats was 3.5 +/- 0.05 d. The mesor, amplitude
      and acrophase value were 10.0 +/- 0.3 g/d, 4.4 +/- 0.2 g/d and 3.5 +/- 0.3
      radian, respectively. The cycle of body-weight change of the Zn-deficient rats
      was well synchronized with that of feed intake. The parameters of the feed intake
      cycle had a high correlation to the corresponding parameters of body-weight
      change (mesor: r = 0.846; amplitude: r = 0.771; period: r = 0.925; acrophase: r =
      0.452). With the supplementation of Zn (0.95-3.80 mg/kg of the Zn-deficient
      diet), cyclic variations in feed intake and body-weight change were also found.
      The mesor, amplitude and period of feed intake cycle were is good correlation
      with Zn intake (r = 0.856, p < 0.001, r = 0.804, p < 0.001 and r = 0.613, p <
      0.01, respectively). The cycle of feed intake of the rats fed a Zn-free diet was
      simulated to be: mesor 9.7 +/- 0.1 g/d, amplitude 6.5 +/- 0.1 g/d and period 3.4
      +/- 0.02 d. The concentration of Zn intake given the half-maximal value of the
      amplitude was assumed to be 56 +/- 1 microgram/d.

PMID- 9268922
TI  - Inhibition of beta-carotene and astaxanthin of NADPH-dependent microsomal
      phospholipid peroxidation.
AB  - To evaluate the antioxidant effects of beta-carotene and astaxanthin, rat liver
      microsomes were exposed to a mixture of chelated iron (Fe3+/ADP) and NADPH. The
      carotenoids (190 pmol/mg protein) were incorporated into some of these microsomal
      membranes, and phospholipid hydroperoxides (PLOOH), thiobarbituric acid reactive
      substances (TBARS) and endogenous alpha-tocopherol content were measured over
      time after the initiation of oxidant stress. In control microsomes, oxidant
      stress led to accumulation of 1,865 (+/- 371) pmol PLOOH/mg protein during the
      initial 10-min peroxidation reaction, followed by a more gradual decrease during
      the subsequent 20-min of reaction. PLOOH accumulation during the initial 10-min
      reaction period was reduced to 588 (+/- 169) pmol/mg protein with beta-carotene
      present and 800 (+/- 288) pmol/mg protein with astaxanthin present. During the
      following 20-min of incubation, PLOOH levels declined in the carotenoid
      supplemented microsomes but continued to increase at a slower rate in control
      preparations. TBARS did not show such large accumulation as observed in PLOOH
      during the initial 10-min incubation in any microsomal sample. The presence of
      carotenoids in the microsomal membrane partially inhibited the loss of alpha
      tocopherol, especially during the later phase of oxidant stress. When lipid
      peroxidation is generated by membrane-bound cyt-P450, the specific measurement of
      PLOOH clearly demonstrates that the presence of carotenoids provides antioxidant
      protection.

PMID- 9268923
TI  - Adaptation of rate of organic acid production of hindgut bacteria to chronic
      intake of galactooligosaccharide in the rat.
AB  - We studied the adaptational effect of galactooligosaccharide (GOS) on the
      concentration of organic acids in cecal content, fecal water content and organic
      acid production from GOS in cultures with the cecal inocula of rats fed GOS for
      1, 2, 7 or 21 d. The fecal water content of rats fed GOS for 1 d was higher than
      that of the controls. The concentration of each organic acid in the cecal
      contents was affected by diet, not by the time of adaptation. In in vitro
      fermentation, lactic acid was produced by rapidly and remained in the cultures
      with homogenates of rats fed GOS for 1 d. Acetic acid in the cultures of the GOS
      diet rats' cecal homogenates was produced more rapidly than that of the controls
      on days 2, 7 and 21 of adaptation. Propionic acid was produced more rapidly in
      the GOS homogenate cultures than in that of the controls on day 2. Butyric acid
      in the cultures from the GOS-fed rats was produced more rapidly than that of the
      controls on days 2 and 21. These results suggest that the time period of GOS
      feeding influenced the production rate of each organic acid, and the changes
      varied among acids.

PMID- 9268924
TI  - Effect of long-term alcohol administration on bone metabolism in rats.
AB  - The purpose of this study was to investigate the effects of different degrees of
      alcohol ingestion on bone strength and mineral density. Three different groups of
      growing female rats were administered different doses of an alcohol-water
      solution for a period of 6 months. These three groups were divided into: 1) the
      control group, which was only given water; 2) the moderate group, which was given
      5% ethanol solution for only 2 h per day; and 3) the excess group, which was
      given only 5% ethanol solution for 163 days. This ethanol consumption induced no
      detrimental effect on biochemical parameters including liver function. The
      moderate group showed significantly higher (p < 0.05) levels of proximal
      metaphysis as compared to the control group, while there was no difference
      between the excess group and the control group. Similarly, in comparison to the
      control group, the moderate group exhibited a significant increase (p < 0.001) in
      bone mechanical strength, while the excess group showed either the same or
      decreased bone stiffness. These results indicate that alcohol intake has both
      beneficial and hindering effects on the skeleton, depending on the concentration
      and frequency of ethanol intake.

PMID- 9268925
TI  - The effect of methyl linoleate hydroperoxides and radical initiator 2,2'-azobis
      (2-amidinopropane) dihydrochloride on antibody production by mouse spleen cells.
AB  - Methyl linoleate hydroperoxides (MLHPO) and 2,2'-azobis (2-amidinopropane)
      dihydrochloride (AAPH), a widely used free radical initiator, were examined for
      effects on antibody production by spleen cells using plaque-forming cell response
      against sheep red blood cells (SRBC). The in vitro primary antibody response was
      enhanced in the presence of MLHPO at a concentration range of 2-20 microM or AAPH
      at 0.1 microM, but was suppressed with higher concentrations of these compounds.
      In the in vitro secondary antibody responses, both MLHPO and AAPH failed to
      increase plaque-forming cell response above that of the control culture.
      Following the oral administration of MLHPO (2.29 g/kg) four times to mice, in
      vivo primary plaque-forming cell response was significantly suppressed. After, a
      single intraperitoneal injection of AAPH (60 mg/kg) to mice, in vitro primary
      plaque-forming cell response was also suppressed. These findings suggest that
      primary antibody response can be affected by lipid hydroperoxides and oxygen
      radicals in vivo.

PMID- 9268926
TI  - Role of ornithine transport into mitochondria in urea synthesis of rats treated
      in thyroid hormone.
AB  - The purpose of this study was to find whether or not the ornithine transport into
      mitochondria regulated urea synthesis when the thyroid status is manipulated.
      Experiments were done on three groups of rats: given 6-propyl-2-thiouracil (PTU,
      a thyroid inhibitor) without triiodothyronine (T3) treatment, treated with PTU+T3
      or receiving neither PTU nor T3 (control). The urinary excretion of urea, liver
      concentration of ornithine and ornithine transport into isolated hepatic
      mitochondria in rats given PTU+T3 were significantly lower than in rats given PTU
      alone. Ornithine transport was significantly inhibited by the addition of lysine
      specifically. This response was achieved well within the physiological
      concentration of lysine. Compared with rats given PTU without T3 treatment, the
      liver concentration of lysine was significantly higher in rats treated with
      PTU+T3 and control rats. Ornithine transport into hepatic mitochondria was
      closely correlated with the excretion of urea. The results suggest that the
      greater ornithine transport in the hypothyroid (PTU alone) rats is likely to
      stimulate urea synthesis. A thyroid hormone-induced increase in lysine
      concentration may be at least partly responsible for the changes in ornithine
      transport into mitochondria.

PMID- 9268927
TI  - Preventive effect of whey hydrolysate formulas for mothers and infants against
      allergy development in infants for the first 2 years.
AB  - We studied the preventive effect against allergies in infants who and whose
      mothers consumed hypoallergenic formulas until 6 months after birth. Mother and
      infant pairs were divided into three groups, and the infants were monitored for
      the development of allergies for the first 2 years. In the MD group (n = 102; n =
      number of infants), the mothers were given a hypoallergenic formula for mothers
      (MOM HA), which contained hydrolyzed whey protein as the only protein source, as
      a substitution for cow's milk during late pregnancy and lactation. In the CD
      group (n = 127), the mothers were given cow's milk during the corresponding
      period. All infants in the MD and CD groups were exclusively breast-fed or mixed
      fed with breast milk and hypoallergenic infant formula (NAN HA), which contains
      the same hydrolyzed protein as MOM HA. In the AF group (n = 54), the mothers
      consumed MOM HA and their infants were mixed-fed with breast milk and a cow's
      milk-based adopted infant formula during the corresponding period. In the MD
      group, no infants were positive to cow's milk-specific immunoglobulin E (RAST) at
      4 months of age, in contrast to 6% and 3% of infants in the CD and AF groups,
      respectively. The infants in the MD group showed low incidence of various
      allergies, especially of eczema, as compared to the CD and AF groups. These
      results suggest that consumption of cow's milk by mothers and cow's milk-based
      formula feeding to infants elevate the risk of allergies in infants, and that
      consumption of hypoallergenic formula for pregnant and lactating women and for
      infants could be helpful in preventing allergy development in infants.

PMID- 9268928
TI  - Maximal stationary metabolic rate in free-moving rats.
AB  - This paper provides a procedure for estimating the maximal stationary metabolic
      rate (SMRmax) in free-moving rats. The SMRmax was estimated by simultaneously
      comparing energy expenditure with motor activity measured at 10 min intervals for
      24 h. The SMRmax was close to but naturally higher than the resting metabolic
      rates determined by other conventional methods. The coefficient of variation for
      3 consecutive days was below 3%. The ratio of SMRmax to daily minimum energy
      expenditure was 1.25 in young rats and 1.19 in adult rats. SMRmax is a useful key
      parameter for analyzing daily energy expenditure and behavior.

PMID- 9268929
TI  - Stimulatory effect of phytin on acid production by Lactobacillus casei.
AB  - The stimulatory effect of phytin added to skim milk on acid production of
      Lactobacillus casei was examined. Phytin stimulated acid production of L. casei
      fairly well. The stimulatory effect of phytin on acid production was not shown
      when phytin was treated with Dowex 50 (H+) and neutralized by NaOH solution. The
      incinerated product of phytin maintained almost equal stimulatory effect on acid
      production as that before processing. The addition of Mn2+ in the amount
      contained in a reagent phytin augmented the stimulatory effect on acid production
      markedly. The further addition of Fe3+, Ca2+, Mg2+ and PO4(3-) in amounts
      corresponding to their contents in the preparation of phytin as well as Mn2+
      increased the effect slightly. The four preparations of phytin contained 0.045
      0.20% of Mn, and the greater the Mn content was, the greater the potentiation of
      acid production.

PMID- 9268930
TI  - FDA begins to act against black box excimer lasers.

PMID- 9268931
TI  - Halos after PRK.

PMID- 9268932
TI  - PRK after RK.

PMID- 9268933
TI  - Permalens hydrogel intracorneal lenses for spherical ametropia.
AB  - PURPOSE: To assess the efficacy, stability, and safety of Permalens hydrogel
      intracorneal lenses for the correction of spherical ametropia 6 years after
      implantation. METHODS: Implantation of intracorneal hydrogel lenses was performed
      by the same surgeon (JIBM) in five aphakic and five high myopic eyes. The lens
      closet to corneal vertex refraction was used. Refractive outcomes, keratometry,
      keratography, endothelial cell count, and corneal topography were studied.
      RESULTS: Corneal tolerance to the hydrogel implants was maintained throughout for
      6 years with no alteration in endothelial cell count. All myopic eyes showed
      regression of achieved correction. The aphakic eyes showed no statistically
      significant difference between the results at 1 month and those obtained at 1 and
      6 years. CONCLUSIONS: Hyrdogel intracorneal lenses are well tolerated and the
      refractive results are stable in aphakic patients. They may be considered when
      intraocular lenses cannot be placed in aphakic patients, but are not now in
      clinical use.

PMID- 9268934
TI  - Excimer laser photorefractive keratectomy for hyperopia.
AB  - OBJECTIVE: To prospectively study excimer laser correction of hyperopia, with a 1
      year followup. METHODS: Eleven consecutive hyperopic eyes (10 phakic and 1
      aphakic) underwent correction of hyperopia using the Summit Technology SVS Apex
      Plus excimer laser. Data collection included cycloplegic refraction, spectacle
      corrected visual acuity, contrast sensitivity, corneal haze, manual keratometry,
      and videokeratography. Prior to treatment the mean hyperopic spherical equivalent
      refraction (corneal plane) was +5.80 diopters (D) (SD2.10). The mean attempted
      correction was +3.09 D at the corneal plane. RESULTS: Refractive data for the
      group showed a mean overcorrection at 1 month of +3.18 D. This regressed slightly
      before stabilizing at 3 months, with a mean overcorrection of +1.88 D. Thereafter
      there was no statistically significant fluctuation in refraction (p = 0.67). The
      amount of overcorrection and regression was greater in eyes that received higher
      corrections. Changes in manual keratometry and videokeratography mirrored the
      attempted correction more closely than refraction, although stabilization did not
      occur until 6 months. CONCLUSIONS: Because the hyperopic correction achieved when
      measured by refraction was greater than expected, algorithms should be adjusted.
      The hyperopic erodible disc and Axicon lens system is capable of treating low to
      moderate amounts of hyperopia.

PMID- 9268935
TI  - Effect of transforming growth factor beta 1 on stromal haze following excimer
      laser photorefractive keratectomy in rabbits.
AB  - BACKGROUND: Transforming growth factor beta (TGF-beta) has been shown to affect
      wound repair. Anti-transforming growth factor beta 1 antibodies have been shown
      to neutralize its activity. METHODS: Seventeen New Zealand White rabbits
      underwent unilateral photorefractive keratectomy followed by corneal staining
      with dichlorotriazinyl fluorescein. Three groups received topical transforming
      growth factor beta 1: 1 microgram/ml, 10 micrograms/ml, and 100 micrograms/ml;
      one group topical anti-transforming growth factor beta antibody (200
      micrograms/ml); and a control group vehicle only. Corneal haze was graded from 0
      to 4, weekly. Rabbits were sacrificed at 5 weeks and histopathological analysis
      and fluorescence microscopy performed. RESULTS: All treated eyes developed haze
      and had epithelial erosions. No statistically significant differences in haze
      score were seen among individual treatment groups (Kruskal Wallis p > 0.05). The
      anti-transforming growth factor beta antibody group had less haze than all other
      groups at every week after the first. Comparing all transforming growth factor
      beta 1 treated eyes as one group to the antibody group, significantly less haze
      was seen at weeks 3 and 4 in the antibody treated group (p = 0.028 and 0.013,
      respectively). This study is limited by small group size and further studies are
      needed to confirm these results. CONCLUSION: TGF-beta may be involved in stromal
      haze formation, and topical anti-TGF-beta 1 antibody may help reduce the
      development of stromal haze.

PMID- 9268936
TI  - Intraocular lens power calculation for cataract surgery after photorefractive
      keratectomy for high myopia.
AB  - OBJECTIVE: To assess intraocular lens (IOL) power calculations in patients
      undergoing cataract surgery after excimer laser photorefractive keratectomy (PRK)
      for myopia. METHODS: Four eyes of two patients underwent phacoemulsification with
      IOL implantation after PRK for myopia. The estimated refractive error that would
      have been induced had the IOL predicted for emmetropia been implanted was
      calculated using SRK-II, SRK/T, Holladay, and Binkhorst formulas. Manual
      keratometry and videokeratography-simulated keratometry values measured before
      surgery were used. Keratometry values calculated by subtracting the refractive
      change induced by the excimer laser PRK from the manual keratometry or
      videokeratography-simulated keratometry values measured before PRK were also
      used. Both spectacle and corneal plane calculations were performed. RESULTS:
      Manual keratometry and videokeratography-simulated keratometry values
      underpredicted the IOL power. Corneal plane manual or videokeratography
      refraction-derived keratometry calculations were most accurate using the SRK/T
      formula, while spectacle plane calculations were most accurate using the SRK-II
      formula. In both methods the calculated refractive error was within 0.52 diopters
      (D) for the emmetropic lens power predicted. Statistical analysis was not
      performed. CONCLUSIONS: Refraction-derived keratometric values provided the most
      accuracy in calculating IOL powers. Our results suggest the SRK/T formula was the
      most accurate for corneal plane calculations, while the SRK-II formula was the
      most accurate for spectacle plane calculations.

PMID- 9268937
TI  - The suction bridge for radial keratotomy may avoid late hyperopic shift.
AB  - BACKGROUND: Radial keratotomy may induce late hyperopic shift. We present data on
      140 consecutive eyes with a follow-up of up to 3 years that underwent radial
      keratotomy with the RK suction bridge. METHODS: We conducted a retrospective
      study of 140 consecutive eyes that had radial keratotomy between 1987 and 1994.
      Mean preoperative spherical equivalent was -5.21 D (range -2.00 to -9.75 D). All
      operations were performed by one surgeon (JHK) with the RK suction bridge. A
      suction ring maintaining physiological intraocular pressure immobilized the eye
      and left a peripheral rim of uncut cornea. The ring incorporated an eccentric
      bridge that guided the radial keratotomy knife. The knife setting was 90% of the
      central corneal thickness, measured by pachymetry. Spherical equivalent
      refraction and spectacle corrected visual acuity were measured at 1 week, 1, 3, 6
      months, 1 year, and 3 years after radial keratotomy. RESULTS: The mean
      preoperative spherical equivalent refraction of -5.21 D dropped to -0.43 D at 1
      week (n = 136), -0.71D at 1 month (n = 120), -0.85 D at 3 months (n = 95), -0.74
      D at 6 months (n = 73), -0.77 D at 12 months (n = 79), and -0.85 D at 3 years (n
      = 67). Compared to 1 month spherical equivalent, at 3 years three eyes (4.4%) had
      moved > = or 1.00 D toward hyperopia. One eye (1.4%) shifted by 1.25 D. Paired t
      tests of mean spherical equivalent refraction did not reveal significant shifts
      toward hyperopia. Mean preoperative spectacle-corrected visual acuity was
      slightly diminished at 1 week and was equal or better thereafter. CONCLUSIONS:
      Our 3-year data suggest that a late hyperopic shift following radial keratotomy
      may be prevented if an intact peripheral rim is maintained and cutting depth does
      not exceed 90% of the lowest corneal thickness.

PMID- 9268938
TI  - Radial keratotomy enhancements for residual myopia.
AB  - BACKGROUND: A systematic method of performing radial keratotomy enhancements in
      undercorrected eyes may increase accuracy and predictability and decrease the
      number of procedures required. A consecutive series of 372 radial keratotomy
      procedures, including 110 eyes that received enhancements under a systematic
      protocol, was evaluated. METHODS: Radial keratotomy was performed using the
      Reliable Keratotomy software, which uses the Thornton nomogram for primary radial
      keratotomy and provides a systematic method of performing enhancements. RESULTS:
      Ninety eyes (24%) received one enhancement, 16 eyes (4%) received two
      enhancements, and four eyes (1%) received three enhancements. Mean final
      spherical equivalent refraction was -0.44 D (-4.00 to +1.875 D, SD 0.86) for eyes
      that did not receive enhancements and -0.44 D (-2.50 to +1.00 D, SD 0.61) for
      eyes that had enhancements. Mean final residual myopia for the entire cohort was 
      0.44 D (-4.00 to +1.875 D, SD 0.79). At final examination, 242 (65%) eyes had a
      refraction within +/- 0.5 D and 298 (80%) within +/- 1.00. Among eyes that
      received enhancements, 75 (68%) had a refraction within +/- 0.50 D, and 89 (81%)
      within +/- 1.00 D; 40 eyes (36%) had uncorrected visual acuity of 20/20 or
      better, 99 eyes (90%) 20/40 or better, and all but one eye (99%) 20/80 or better
      at the final postoperative examination. Among the entire cohort, 130 eyes (35%)
      had uncorrected visual acuity of 20/20 or better, 312 (84%) had 20/40 or better,
      and 350 (94%) had 20/80 or better. No eye lost more than one line of spectacle
      corrected visual acuity. CONCLUSION: A systematic approach to enhancement of
      undercorrected eyes after radial keratotomy, combined with accurate surgery, may
      reduce the need for multiple enhancements as well as the overcorrection rate, and
      provide improved uncorrected visual acuity.

PMID- 9268940
TI  - Proper method for calculating average visual acuity.

PMID- 9268939
TI  - Traumatic aphakia treated with an iris prosthesis/intraocular lens or
      epikeratophakia.
AB  - OBJECTIVE: We retrospectively analyzed the visual results and postoperative
      complications associated with severely traumatized eyes in which aphakia was
      corrected with epikeratophakia or a sutured iris prosthesis/intraocular lens
      (IOL). METHODS: Fourteen eyes (14 patients) with traumatic aphakia and severe
      anterior segment complications were corrected either with epikeratophakia or a
      sutured iris prosthesis/IOL. All eyes lacked lens capsule or iris support for an
      IOL. The surgical technique of implanting an iris prosthesis/IOL employed
      transcleral suturing in the ciliary sulcus combined with penetrating
      keratoplasty. RESULTS: In the eight eyes treated with epikeratophakia, four (50%)
      had spectacle-corrected visual acuity of 20/40 or better. Almost all of these
      eyes lost one or two Snellen lines of baseline spectacle-corrected visual acuity.
      Few complications occurred after epikeratophakia; none were severe. Of six eyes
      with penetrating keratoplasty and a sutured iris prosthesis/IOL or a sutured
      posterior chamber IOL, two (33%) achieved a visual acuity of 20/40 or better. In
      the IOL group, severe complications occurred, including posterior dislocation of
      the lens and secondary glaucoma. CONCLUSIONS: The surgical correction of aphakia
      in severely traumatized eyes requires specialized surgical techniques.
      Epikeratophakia is a low-risk operation that can be performed in eyes in which an
      IOL is contraindicated. The iris prosthesis/IOL technique results in good
      cosmetic results; however, due to complications, this technique should be used
      with caution.

PMID- 9268941
TI  - Bilateral cataract after phakic posterior chamber top hat-style silicone
      intraocular lens.
AB  - BACKGROUND: New strategies have been developed for surgical treatment of high
      myopia. Recently, implantation of minus power posterior chamber intraocular
      lenses (IOL) into phakic eyes has been introduced. METHODS: We report a 37 year
      old female patient who developed bilateral anterior subcapsular cataract 7 years
      after minus-power, top hat-style silicone posterior chamber IOL implantation in
      Russia. The corrected visual acuity was right eye 20/200 and left eye 20/63.
      Because of the high myopia and the posterior chamber IOL in her phakic eyes,
      biometry for IOL calculation gave contradictory results. Both posterior chamber
      IOLs were found to be adherent to the crystalline lenses. After posterior chamber
      IOL explantation and phacoemulsification, intraoperative retinoscopy was
      performed. With this aphakic refraction, the IOL power was calculated and
      implanted. The explanted posterior chamber IOLs were examined by scanning
      electron microscopy. RESULTS: After bilateral operation the corrected visual
      acuity increased to right eye 20/32 and left eye 20/40, respectively. On scanning
      electron microscopy, a membranous structure of unknown origin was noted on the
      entire surface of the explanted posterior chamber IOLS. CONCLUSION: There is a
      potential risk of cataract formation after implantation of this top hat-style
      silicone posterior chamber IOL. If cataract extraction in this specific situation
      is needed, a different approach for calculating the aphakic IOL power is
      necessary, such as intraoperative retinoscopy.

PMID- 9268942
TI  - Hyperopic shift induced by high altitude after radial keratotomy.
AB  - BACKGROUND: The collagen fibrils embedded in the ground substance of the stromal
      lamellae provide the structural support for the cornea. When the stromal lamellae
      are cut in a radial keratotomy surgical procedure, the remaining uncut lamellae
      carry the tensile forces. METHODS: We studied two expert climbers who had
      bilateral radial keratotomy before participating in six climbs of extreme
      altitude, including Mount McKinley and above 7500 m (24,606 ft) on Mount Everest.
      RESULTS: Whenever either climber was exposed to altitudes greater than
      approximately 5000 m (16,405 ft) for more than a day, their refraction would
      become +3.00 D or more hyperopic and remain so al long as they were at or above
      this altitude. Visual acuity slowly returned to normal after descent. CONCLUSION:
      It appears that in the presence of significantly reduced atmospheric pressure
      and/or oxygen there is a greater effect of radial keratotomy in some patients,
      making the cornea more vulnerable to changes in shape. The cornea appears to
      respond by further flattening, exacerbating the intended surgical effect and
      producing a refractive shift toward hyperopia.

PMID- 9268943
TI  - Corneal iron line associated with steep central islands after photorefractive
      keratectomy.
AB  - PURPOSE: To report a new corneal iron deposit after excimer laser photorefractive
      keratectomy (PRK). METHODS: Two patients with symptomatic persistent steep
      central islands were noted to have a corneal iron ring at 6 months to 1 year
      after surgery. This is different from the central iron spot noted in most
      patients at 1 year. RESULTS: One patient had repeated PRK with improvement of his
      symptoms and resolution of the iron ring. CONCLUSIONS: A corneal iron ring after
      excimer laser PRK suggests the presence of a persistent steep central island of
      stromal origin. Since corneal iron deposition signifies chronicity, symptomatic
      patients should be retreated as resolution of the steep central island is not
      likely to occur.

PMID- 9268944
TI  - Do doctors know when their patients don't? A survey of doctor-patient
      communication in lung cancer.
AB  - OBJECTIVES: a) To determine how much patients with recently diagnosed lung cancer
      know about their illness and its treatment, and b) to find out if doctors know
      what their patients know and what they don't. PATIENTS AND METHODS: One hundred
      patients with recently diagnosed lung cancer, who were undergoing radiotherapy or
      chemotherapy, were interviewed to determine their view of their diagnosis, the
      extent of the cancer, the intent of treatment, and the risks and benefits of
      treatment. Their attending physicians' view were elicited contemporaneously,
      using a self-administered questionnaire. The principle outcome measure of the
      study was the level of agreement between the views of the patients and the
      doctors about the disease, the treatment, and the prognosis. Concordance between
      doctors' and patients' views was expressed in terms of percentage agreement, and
      Kappa (kappa). RESULTS: Ninety-nine percent of the patients knew that they had
      lung cancer. Sixty-four percent (64%) agreed with their doctor about the extent
      of the disease (kappa = 0.48). Most of those who disagreed underestimated the
      extent of their cancer. Seventy-two percent (72%) agreed with their doctor about
      the intent of treatment (kappa = 0.49). Thirty-six percent (36%) agreed with
      their doctors about their probability of cure, (kappa = 0.17): most of those who
      disagreed systematically overestimated it. Sixty-eight patients were receiving
      palliative treatment. Of these, 56% agreed with their doctor about the
      probability of symptomatic benefit (kappa = 0.42), but only 14% agreed with their
      doctor about the probability that the treatment would prolong life (kappa =
      0.06). Doctors frequently failed to recognize their patients' misconceptions
      about the intent of treatment and the prognosis. CONCLUSION: Many patients did
      not understand their situation well enough to make a truly autonomous treatment
      decision, and their doctors often failed to recognize this.

PMID- 9268945
TI  - Ganglioside expression in lung cancer cell lines.
AB  - Gangliosides are complex glycolipid constituents of cell membranes. They are
      involved in many biological functions including cell-cell recognition, cell
      matrix attachment, cell growth and cell differentiation. Analysis of tumor
      associated gangliosides may aid in the characterisation of tumour cells and their
      degree of malignant transformation. We have characterised a total of eight lung
      cancer cell lines (four small cell and four non-small cell lung cancer) with
      respect to ganglioside and alpha v integrin receptor expression. Ganglioside GD3
      was detected using the monoclonal antibody R24. Ganglioside GM1 was detected
      using the beta-subunit of cholera toxin. Ganglioside 9-O-acetyl GD3 and the alpha
      v integrin receptor were measured using commercially available monoclonal
      antibodies. Our results indicate that small cell lung cancer cell lines express
      significant levels of GD3 and 9-O-acetyl GD3. Ganglioside GM1 and alpha v
      integrin receptor were not specific to any histological subtype. The expression
      of ganglioside GM1 and GD3 was independent of cell-cycle phase. We conclude that
      GD3 and 9-O-acetyl GD3 expression may be additional markers of the Small Cell
      Lung Cancer phenotype, but their significance is unknown. Therefore a
      characteristic ganglioside pattern cannot be defined according to histological
      subtype. alpha v integrin receptor expression is not unique to cells expressing
      GD3.

PMID- 9268946
TI  - Infiltration of lung carcinomas with macrophages of the 27E10-positive phenotype.
AB  - In order to gain insight into the role of macrophages in human lung carcinomas,
      we investigated material from 35 lung carcinomas and 5 healthy lungs with 4
      different antibodies (CD68, MRP8, MRP14, 27E10) recognizing different macrophage
      subtypes. Infiltration with CD68-positive macrophages was highest and comparable
      in healthy lungs and lung carcinomas. Compared to healthy lungs, the infiltration
      of MRP8- and MRP14-positive macrophages was reduced in lung carcinomas while the
      number of 27E10-positive cells was enhanced. No difference in the infiltration of
      macrophages was observed between the different histological subtypes of
      carcinomas such as squamous carcinoma, small lung carcinoma, adenocarcinoma and
      bronchio-alveolar carcinoma. Furthermore, we present a highly suitable technique
      for the isolation and enrichment of macrophages from human lung carcinomas
      resulting in a 5-10 fold enrichment and a yield of e.g. 2-3 x 10(6) 27E10
      positive macrophages/g tumor biopsy. Together with the recent findings that 27E10
      positive macrophages are prevalent in early acute inflammation and release
      cytotoxic mediators and to inhibit tumor cell proliferation our findings suggest
      that 27E10-positive macrophages may play a role in antitumor cytotoxicity in
      human lung carcinomas.

PMID- 9268947
TI  - Results of surgery for bronchogenic carcinoma located in the aortic window.
AB  - Because of its critical location, lung cancer located in the aortic window can
      cause complications affecting the pulmonary artery trunk, aortic arch and
      esophagus. The results of surgical treatment are poor; however, there are few
      long-term survivors. In an attempt to define the indications for extended
      surgery, we evaluated eleven patients with non-small cell lung cancer. The tumors
      were classified according to their clinical extent of invasion as Type A
      (invading the anterior mediastinum including the central part of the pulmonary
      artery), Type B (invading upwardly to the mediastinum through the aortic window)
      or Type C (invading the posterior mediastinum including the thoracic aorta or
      esophagus). In the five patients with type A invasion, no metastases to the upper
      mediastinal lymph nodes other than the subaortic lymph nodes were found. The
      three patients with type B invasion had many metastases to the upper mediastinal
      lymph nodes. There were no metastases in the upper mediastinum in any of these
      patients with type C invasion, but metastases were found in a lower mediastinal
      lymph node #9, and a carinal lymph node. Each group clearly demonstrated a
      different site of mediastinal lymph nodes metastasis. The long term result was
      good in Type A invasion, in contrast to Type B or C invasion. Our classification
      may be useful for planning one's surgical approach to advanced lung cancer of the
      aortic window.

PMID- 9268948
TI  - Efficacy of platinum-based regimens in non-small cell lung cancer. A negative
      report from the Cuneo Lung Cancer Study Group.
AB  - Combination chemotherapy with cytotoxic agents is the regular treatment for
      patients with advanced non-small cell lung cancer (NSCLC), good performance
      status, and no major clinical contraindications. Since the early 1980s, platinum
      based chemotherapy is the cornerstone of this treatment, while combinations
      containing long-acting alkylating agents have been nearly abandoned, and
      represent a sort of historical treatment. Nevertheless, the real survival
      benefits of cisplatin are uncertain and still debated. To attempt an answer, the
      Cuneo Lung Cancer Study Group (CuLCaSG) carried out a clinical trial comparing a
      platinum (MVP) versus a non-platinum-based combination chemotherapy (MACC). The
      study comprised 156 patients with advanced NSCLC randomly assigned to the two
      treatment arms. MACC and MVP chemotherapies were given as originally described
      and continued until progression of disease, unacceptable toxicity, or refusal by
      the patient. For a medium of four cycles of MVP and three cycles of MACC, the
      median dose intensity (DI) reached was, respectively, 95% and 100% of the
      intended (P = 0.0132). In all, 27 objective responses (1 complete and 16 partial
      responses in patients allocated to MVP versus 10 partial responses of the MACC
      group) were observed. Median progression-free and global survivals were,
      respectively, 21 and 34 weeks for MVP and 20 and 31 weeks for MACC (non
      significant differences). The treatment plan was found non-significant also
      multivariate analysis of survival. Toxicity was rather similar in the two arms,
      except for more severe neurological toxicity, anemia, thrombocytopenia, nausea,
      and vomiting in patients on MVP. Alopecia was more common after MACC. Subjective
      tolerance to treatment, and perception of physical and psychological well-being
      were rated similarly by patients of both groups. In conclusion, MVP was
      moderately more active than MACC, and showed a foreseeable and reversible
      toxicity, of a low-medium grade. However, this CuLCaSG study failed to
      substantiate any survival benefit from the use of platinum in combination with
      other cytotoxic agents.

PMID- 9268949
TI  - Carboplatin as radiosensitizer in non-small cell lung cancer after cisplatin
      containing chemotherapy. A phase I study of a groupe francais de pneumo
      cancerologie (G.F.P.C.).
AB  - A Phase I trial of carboplatin therapy was performed on patients with locally
      advanced non-small cell lung cancer who had been previously treated with
      cisplatin, mitomycin and a vinca aklaloid. This was administered as a daily bolus
      infusion or as a continuous infusion for 6 weeks with concurrent daily thoracic
      radiation. All patients had to be objective responders or to show no change after
      chemotherapy. The carboplatin was started at 10 mg/m2 per day, and increased to
      15 mg/m2 per day and 20 mg/m2 per day, if treatment was feasible in successive
      cohorts of at least six patients. The radiation therapy consisted of 62-66 Gray
      on the tumor and the ipsilateral mediastinal nodes, 50 Gray on the mediastinum
      and 40-45 Gray on the supraclavicular lymph nodes. Twenty-nine patients took part
      in this study. Thrombocytopenia was the principal dose-limiting toxicity, with 15
      mg/m2 per day of bolus or continuous infusion. Other toxicities included a fall
      in haemoglobin level, a fall in white-blood cell count, nausea and vomiting. The
      median survival time was 12 months, but the response rate cannot be determined
      among patients selected on the basis of response to chemotherapy. The recommended
      Phase II dose for patients previously treated with cisplatin containing
      chemotherapy, is 10 mg/m2 per day of either a bolus or continuous infusion.

PMID- 9268950
TI  - Phase II study of a one hour paclitaxel infusion in combination with carboplatin
      for advanced non-small cell lung cancer.
AB  - PURPOSE: To determine the activity, toxicity, and optimal dose of paclitaxel when
      given by one hour infusion combined with carboplatin in advanced non-small cell
      lung cancer (NSCLC). PATIENTS AND METHODS: Thirty-seven previously untreated
      patients with stage IIIB or IV NSCLC were enrolled. Paclitaxel was administered
      by one hour infusion at a dose of 175 mg/m2 for the first cycle, and was
      escalated up to 255 mg/m2 over successive cycles if tolerated. In the absence of
      toxicity, the carboplatin dose was kept constant at an area under the
      concentration-time curve (AUC) of 6. Cycles were repeated at 3-week intervals
      until progression or intolerable toxicity occurred. RESULTS: Thirty-six patients
      were evaluable for toxicity and survival, and thirty-five for responses. The
      partial response rate was 10 of 35 (29%) and there were no complete responses.
      The median duration of response was 4.8 months (range 0.5-11.7 months). The
      median survival duration was 6.5 months, and 1 year survival was 31%. The mean
      paclitaxel dose was 188 mg/m2. Treatment was generally well tolerated. Four
      patients (11%) had febrile neutropenia. Five patients (14%) had grade 3
      neuropathy, and 4 (11%) had grade 3 nausea and vomiting. Minor toxicities
      included alopecia, myalgias, arthralgias and stomatitis. CONCLUSIONS: Paclitaxel
      and carboplatin is a well-tolerated regimen that can safely be given by a one
      hour paclitaxel infusion. The modest response rate observed in this study may be
      due to either the low dose-intensity of paclitaxel or the short infusion
      duration. Further trials to optimize the relative doses of paclitaxel and
      carboplatin are needed.

PMID- 9268951
TI  - Vinorelbine and ifosfamide for unresectable non-small cell lung cancer.
AB  - PURPOSE: The study assessed the efficacy of combination therapy with vinorelbine
      and ifosfamide in patients with unresectable non-small cell lung cancer. PATIENTS
      AND METHODS: Forty patients with non-small cell lung cancer whose tumour was
      unresectable by virtue of the extent of disease or severity of impairment of lung
      function and who were considered unsuitable for treatment with a cisplatin based
      treatment were entered onto the study. Thirty-four patients received two cycles
      of treatment and were considered to be evaluable for response. The treatment
      schedule consisted of vinorelbine (Navelbine, Pierre Fabre Medicament) 25 mg/m2
      on days 1 and 8, and ifosfamide 2 g/m2 per day with mesna 0.5 g/m2 three times
      daily given on days 1 to 3; cycles were repeated every 21 days and treatment
      continued in responding patients until progression occurred. RESULTS: Objective
      responses were observed in 12 patients (30%; CI95, 16-44) with one completed
      response (CR) and 11 partial response (PR). CONCLUSION: This schedule achieves
      good levels of response without the use of cisplatin so it is suitable for
      patients whose performance status or concomitant medical condition precludes the
      use of platinum based chemotherapy.

PMID- 9268952
TI  - Intestinal bleeding in disseminated non-small cell lung cancer.
AB  - A case of gastrointestinal bleeding in a 40 year old male with NSCLC is
      presented. Usual diagnostic tools did not reveal the cause of bleeding and a
      laparotomy was necessary to localise and treat the haemorrhage. Intestinal
      metastases have been described in 11% of lung cancer but they rarely produce
      symptoms. However, intestinal metastases may produce gastrointestinal
      perforation, obstruction and very occasionally bleeding. In fact, the present
      report is the second case published of gastrointestinal bleeding from lung cancer
      metastases. In most cases prognosis is poor for these patients with a medium
      survival of a few weeks. Surgery may palliate selected patients but there is no
      evidence that chemotherapy is beneficial.

PMID- 9268953
TI  - Compliance to exercise therapy in older participants with knee osteoarthritis:
      implications for treating disability.
AB  - This investigation examined predictors of compliance with exercise therapy in a
      clinical trial involving older adults with knee osteoarthritis (OA). The study
      sample was partitioned into tertiles by level of compliance to determine its
      effect on several clinical outcome measures in the trial (i.e., knee pain,
      difficulty with activities of daily living, and performance-related disability).
      The participants (N = 439) first completed all baseline assessments and were then
      randomly assigned to one of three treatment conditions: health education control,
      aerobic exercise, or resistance exercise. The two exercise treatments involved a
      3-month center-based phase and a 15-month home-based phase. Variables in five
      categories (i.e., demographic, fitness, health-related quality of life,
      performance-related disability, and prior exercise behavior) were entered as
      predictors of attendance and time spent exercising during each session for three
      different periods of time across the course of the study. Results of these
      analyses revealed that it was possible to explain more variance for time spent
      exercising (approximately 40%) during the first 3 months than for attendance
      (approximately 10%). Furthermore, once participants completed the first 3 months
      of their training, prior behavior was the strongest predictor of exercise
      compliance. In most cases, the regression models accounted anywhere from 26 to
      46% of the variance in attendance or time spent exercising (7 of the 8 P values <
      0.01). In general, demographic, fitness, psychosocial, and disability-related
      measures did not predict compliance with any consistency across the various
      phases of the trial. Analysis of the dose-response data suggest that, in the use
      of aerobic exercise to deter disability in older people with knee OA,
      consideration should be given to prescribing frequent bouts of activity (at least
      3 times each week) of moderate duration (approximately 35 min).

PMID- 9268954
TI  - Exercise training, postprandial hypertriglyceridemia, and LDL subfraction
      distribution.
AB  - The purpose of this study was to examine differences in postprandial
      hypertriglyceridemia (PP-HTG) and low density lipoprotein (LDL) subfraction
      distribution among groups of men and women with different fitness levels. Fifty
      four men and women (ages 30-53 yr) were recruited based on their previous two
      year activity level: sedentary (S), recreational exercisers (R), and endurance
      trained (T). After a 24-h dietary preparation, blood was collected, and LDL
      subfractions were separated and analyzed for cholesterol (C) and apoprotein B100.
      Plasma triglyceride (TG) concentration was assessed before and at 2, 4, 6, and 8
      h after fat meal. PP-HTG was significantly higher for the S group compared with
      the two activity groups. LDL3-C and LDL3-apoprotein B100 were significantly
      higher for the S group compared with the T group and for men compared with women.
      These findings suggest that both recreational and competitive aerobic training
      are associated with a lower TG response after a fatty meal. However, higher
      volume aerobic training may be necessary to reduce the number of dense LDL
      molecules and their cholesterol content.

PMID- 9268956
TI  - Naturally occurring muscle pain during exercise: assessment and experimental
      evidence.
AB  - The objectives were: (i) to present a method for assessing muscle pain during
      exercise, (ii) to provide reliability and validity data in support of the
      measurement tool, (iii) to test whether leg muscle pain threshold during exercise
      was related to a commonly used measure of pain threshold pain during test, (iv)
      to examine the relationship between pain and exertion ratings, (v) to test
      whether leg muscle pain is related to performance, and (vi) to test whether a
      large dose of aspirin would delay leg muscle pain threshold and/or reduce pain
      ratings during exercise. In study 1, seven females and seven males completed
      three 1-min cycling bouts at three different randomly ordered power outputs. Pain
      was assessed using a 10-point pain scale. High intraclass correlations (R from
      0.88 to 0.98) indicated that pain intensity could be rated reliably using the
      scale. In study 2, 11 college-aged males (age 21.3 +/- 1.3 yr) performed a ramped
      (24 W.min-1) maximal cycle ergometry test. A button was depressed when leg muscle
      pain threshold was reached. Pain threshold occurred near 50% of maximal capacity:
      50.3 (+/- 12.9% Wmax), 48.6 (+/- 14.8% VO2max), and 55.8 (+/- 12.9% RPEmax). Pain
      intensity ratings obtained following pain threshold were positively accelerating
      function of the relative exercise intensity. Volitional exhaustion was associated
      with pain ratings of 8.2 (+/- 2.5), a value most closely associated with the
      verbal anchor "very strong pain." In study 3, participants completed the same
      maximal exercise test as in study 2 as well as leg cycling at 60 rpm for 8 s at
      four randomly ordered power outputs (100, 150, 200, and 250 W) on a separate day.
      Pain and RPE ratings were significantly lower during the 8-s bouts compared to
      those obtained at the same power outputs during the maximal cycle test. The
      results suggest that noxious metabolites of muscle contraction play a role in leg
      muscle pain during exercise. In study 4, moderately active male subjects (N = 19)
      completed two ramped maximal cycle ergometry tests. Subjects drank a water and
      Kool-Aid mixture, that either was or was not (placebo) combined with a 20 mg.kg-1
      dose of powdered aspirin 60 min before exercise. Paired t-tests revealed no
      differences between conditions for the measures of exercise intensity at pain
      threshold [aspirin vs placebo mean (+/- SD)]: power output: 150 (+/- 60.3 W)
      versus 153.5 (+/- 64.8 W); VO2: 21.3 (+/- 8.6 mL.kg-1.min-1) versus 22.1 (+/-
      10.0 mL.kg-1.min-1); and RPE: 10.9 (+/- 3.1) versus 11.4 (+/- 2.9). Repeated
      measures ANOVA revealed no significant condition main effect or condition by
      trial interaction for pain responses during recovery or during exercise at 60,
      70, 80, 90, and 100% of each condition's peak power output. It is concluded that
      the perception of leg muscle pain intensity during cycle ergometry: (i) is
      reliably and validly measured using the developed 10-point pain scale, (ii)
      covaries as a function of objective exercise stimuli such as power output, (iii)
      is distinct from RPE, (iv) is unrelated to performance of the type employed here,
      and (v) is not altered by the ingestion of 20 mg.kg-1 acetylsalicylic acid 1 h
      prior to the exercise bout.

PMID- 9268955
TI  - Chromium and exercise training: effect on obese women.
AB  - Chromium supplementation may affect various risk factors for coronary artery
      disease (CAD) and non-insulin-dependent diabetes mellitus (NIDDM), including body
      weight and composition, basal plasma hormone and substrate levels, and response
      to an oral glucose load. This study examined the effects of chromium
      supplementation (400 micrograms.d-1), with or without exercise training, on these
      risk factors in young, obese women. Chromium picolinate supplementation resulted
      in significant weight gain in this population, while exercise training combined
      with chromium nicotinate supplementation resulted in significant weight loss and
      lowered the insulin response to an oral glucose load. We conclude that high
      levels of chromium picolinate supplementation are contraindicated for weight loss
      in young, obese women. Moreover, our results suggest that exercise training
      combined with chromium nicotinate supplementation may be more beneficial than
      exercise training alone for modification of certain CAD and NIDDM risk factors.

PMID- 9268957
TI  - Accentuated antagonism in canine subendocardium is not altered by chronic
      exercise.
AB  - Acetylcholine often affects cardiac action potential repolarization only during
      augmented adrenergic tone, i.e., the phenomenon of accentuated antagonism. Since
      chronic exercise involves repeated changes in autonomic outflow, we determined
      whether it also influenced adrenergic/cholinergic interactions in isolated canine
      cardiac tissue. Using standard micro-electrode techniques in thin ventricular
      subendocardial slices isolated from exercised (EX: 8-10 wk daily exercise) and
      sedentary (SED): 8-10 wk cage rest) dogs, we examined transmembrane potential
      responses to isoproterenol (ISO: 10(-8), 10(-7), 10(-6) M) and to ISO in the
      presence of ACH (10(-5) M). Control transmembrane characteristics at BCL = 500 ms
      were similar for EX (N = 8 dogs) and SED (N = 9 dogs). ISO (10(-6) M) decreased
      action potential duration at 50% repolarization (APD50): EX = -29 +/- 15 ms; SED
      = 11 ms and at 90% repolarization (APD90): EX = -37 +/- 17 ms; and SED = -24 +/-
      14 ms (P > 0.05, EX vs SED). ACH alone did not alter APD. With ACH (10(-5) M),
      delta APD50 with ISO (10(-6) M) was -5 +/- ms and 0 +/- 5 ms for EX and SED,
      respectively; delta APD90 was -8 +/- 4 ms and -8 +/- 7 ms for EX and SED,
      respectively (P > 0.05, EX vs SED). Thus, ACH antagonized ISO-mediated
      acceleration of repolarization equally in both groups. Chronic daily exercise
      does not influence adrenergic/cholinergic interactions at the cellular level.

PMID- 9268958
TI  - Temporal inhomogeneity in brachial artery blood flow during forearm exercise.
AB  - The purpose of this study was to measure the influences of muscle contraction and
      exercise intensity on brachial artery blood flow during incremental forearm wrist
      flexion exercise to fatigue. Twelve subjects performed incremental forearm
      exercise (increments of 0.1 W every 5 min) with their nondominant arms. Doppler
      waveforms and two-dimensional images of the brachial artery were recorded during
      the last 2 min of each stage. Exercise intensities were expressed as a percent of
      the maximal workload achieved (%WLmax). Blood flow was calculated during each of
      the concentric (CP), eccentric (EP), and recovery phases (RP) of the contraction
      cycle. Blood flow during the CP of the contraction did not increase above resting
      values (25.0 +/- 10.5 mL.min-1) at any intensity (100%WLmax = 21.6 +/- 6.5 mL.min
      1). Conversely, blood flow during the EP and RP increased from 25.6 +/- 3.0 to
      169.1 +/- 12.8 (P < 0.05), and from 24.7 +/- 3.1 to 137.9 +/- 19.5 mL.min-1 (P <
      0.05), respectively from rest to maximal exercise. Time averaged blood flow
      increased linearly from rest to maximal exercise (75.3 +/- 26.3 to 334.6 +/-
      141.6 mL.min-1, P < 0.05). Thus, a significant impairment in blood flow occurs
      with concentric contractions during forearm dynamic exercise. The implications of
      a temporal disparity in blood flow to oxygen delivery and skeletal metabolism
      during exercise are discussed.

PMID- 9268959
TI  - Exercise mode and gender comparisons of energy expenditure at self-selected
      intensities.
AB  - The purpose of this study was to compare oxygen consumption (VO2) and energy
      expenditure after 20 min of self-selected submaximal exercise for four modes of
      exercise. Eighteen subjects (9 male and 9 female) first completed a test of
      VO2max during treadmill running. On separate days, subjects then completed 20 min
      submaximal treadmill running (TR), simulated cross-country skiing (XC), cycle
      ergometry (CE), and aerobic riding (AR) exercise. Total VO2 and energy
      expenditure were significantly higher for TR than all other modes for both males
      and females (43.6 +/- 10.4, 39.1 +/- 9.7, 36.1 +/- 7.6, 28.4 +/- 6.1 LO2, for TR,
      XC, CE, and AR, respectively, P < 0.0001). For males and females, heart rate was
      similar during TR and XC and lower during CE and AR (154.8 +/- 14.2, 152 +/-
      13.1, 143.4 +/- 14.9, and 126.2 +/- 12.0 beats.min-1 for TR, XC, CE, and AR,
      respectively, P < 0.0001). Compared with females, males had significantly greater
      VO2 (P < 0.005) and energy expenditure (P < 0.004), while females had higher
      heart rates (P < 0.003). Ratings of perceived exertion (RPE) were not different
      between TR, XC, and CE, but were significantly lower during AR (13.4 +/- 1.3,
      13.6 +/- 0.8, 13.2 +/- 0.9, and 12.6 +/- 1.0 for TR, XC, CE, and AR,
      respectively, P < 0.003). TR elicited the greatest VO2 and energy expenditure
      during self-selected exercise despite and RPE similar to XC and CE. Therefore,
      treadmill exercise may be the modality of choice for individuals seeking to
      improve cardiorespiratory endurance and expend a larger number of kjoules.

PMID- 9268960
TI  - The effect of exercise intensity on lipid peroxidation.
AB  - This study characterizes exercise-induced lipid peroxidation during graded
      aerobic exercise in seven healthy men and women (36.4 +/- 3 yr). Levels of ethane
      and pentane in expired breath during cardiopulmonary exercise stress testing were
      measured at rest, lactic acidosis threshold (LAT), maximal exercise (VO2max), and
      recovery. Serum malonaldehyde (MDA) levels were measured at rest before exercise
      and 5 min after maximal exercise. Expired ethane and pentane flux levels were
      increased above resting levels at LAT, continued to rise at VO2max, then declined
      during recovery. Serum MDA levels were not significantly different before and
      after maximal exercise. Substantial exercise-induced lipid peroxidation (by
      expired ethane and pentane) apparently occurred in healthy individuals at LAT and
      continued to increase at VO2max, yet rapidly attenuated during post-exercise
      recovery. These findings indicate that in healthy individuals physical exercise
      induced lipid peroxidation transiently and that there was a removal of lipid
      peroxidation byproducts during recovery.

PMID- 9268961
TI  - Left ventricular function in response to the transition from aerobic to anaerobic
      metabolism.
AB  - The purpose of this investigation was to study myocardial function at rest,
      during three phases of energy supply, and during recovery. Radionuclide
      angiography was performed during the aerobic phase (phase I, rest-first lactate
      increase), the aerobic-anaerobic transition phase (phase II, first lactate
      increase-second lactate increase), the anaerobic phase (phase III, second lactate
      increase-maximal work performance (Pmax)), and during recovery. Thirty-eight male
      patients (59 +/- 7 d after myocardial infarction) were compared with 19 healthy
      control subjects and 21 sport students of comparable age. Left ventricular
      ejection fraction (LVEF) increased from rest to phase I and from phase I to phase
      II in sports students and control subjects. During phase III, LVEF did not change
      significantly in sports students, but it decreased significantly in control
      subjects. This is in contrast to the patients, who showed an increase of LVEF
      from resting values (47 +/- 3%) to phase I (50 +/- 1%), no change during phase II
      (51 +/- 2%), and a decrease to resting values (45 +/- 2) during phase III. All
      subjects showed an increase in stroke volume (SV) during phase I and II, reaching
      a maximum at phase II. This was evidenced by an improvement of the systolic
      function with a constant left ventricular end-diastolic volume (EDV) in control
      subjects and sports students. In contrast, an improved SV in patients was
      achieved through an increase in EDV and a less distinct increase in the left
      ventricular end-systolic volume (ESV). Maximal LVEF values were measured during
      the first 90 s of recovery in all subjects. Values during recovery are not
      representative of load dependent myocardial function. This increase in LVEF does
      not cause an increase in cardiac output but is a consequence of changes in the
      EDV and ESV, which decrease again immediately after the end of exercise
      performance.

PMID- 9268962
TI  - Lactate and the effects of exercise on testosterone secretion: evidence for the
      involvement of a cAMP-mediated mechanism.
AB  - The effects of swimming and lactate on the release of testosterone were examined
      in male rats. During in vivo experiments, male rats were catheterized via the
      right jugular vein and blood was collected at 0, 10, 15, 30, and 60 min following
      the exercise, or they were catheterized via the right jugular vein and the left
      femoral vein and blood was collected at 0, 2, 5, 10, 15, 30, 60, and 120 min
      after a 10-min infusion at lactate (13 mg.kg-1.min-1). Trunk blood and blood from
      the testicular vein were also collected after 10 min of swimming or water
      immersion. In an in vitro experiment, testicular fragments were challenged with
      lactate (0.01-10 mM) and/or human chorionic gonadotropin (hCG; 0.5 IU.mL-1), and
      the mediobasal hypothalamus (MBH) was challenged with lactate (8 mM). The post
      exercise levels of plasma lactate and testosterone at 10, 15, and 30 min were
      higher than resting levels. Plasma luteinizing hormone (LH) was increased
      following 30 min of swimming. Administration of lactate or hCG increased in a
      dose dependent manner testicular cyclic adenosine 3':5' monophosphate (cAMP) and
      testosterone release. Plasma testosterone increased after swimming and lactate
      infusion. Incubation of MBH with lactate increased the gonadotropin-releasing
      hormone (GnRH) level in the medium. These results suggest that the increased
      plasma testosterone levels in male rats during exercise is at least partially a
      result of a direct and LH-independent stimulatory effect of lactate on the
      secretion of testosterone by increasing testicular cAMP production. Swim-elevated
      plasma LH may be a result of a rise of GnRH caused by lactate.

PMID- 9268963
TI  - Associations between physical activity and risk factors for coronary heart
      disease: the Cardiovascular Risk in Young Finns Study.
AB  - Risk factors such as high serum cholesterol concentration measured in young
      adulthood predict premature coronary heart disease (CHD) in the middle-aged. The
      objective of this study was to analyze the associations between physical activity
      and CHD risk factors--body composition, blood pressure, serum lipids,
      apolipoproteins, and insulin--in children and young adults. The design was a
      cross-sectional study of atherosclerosis precursors in children and young adults
      using a cohort of children and young adults (N = 2,358) aged 9 to 24 years to
      determine indices of physical activity, measurements of anthropometric
      characteristics, blood pressure, serum lipids, apolipoproteins A-I and B, and
      insulin. The results show that a high level of physical activity was associated
      with high serum high density lipoprotein cholesterol (HDL-C) and HDL2-C
      concentrations, and low levels of serum triglycerides (TG), apolipoprotein B and
      insulin in males. However, in females, the influence of physical activity was
      evident only on TG level. In both genders, physical activity was inversely
      associated with obesity. In all these associations, a significant dose-related
      relationship was observed. We found no association between physical activity and
      blood pressure. In conclusion, physical activity is associated with a favorable
      serum lipid profile already during childhood and early adulthood in a dose
      related manner, particularly in males. The promotion of physical activity is
      important in childhood in preventing obesity and premature cardiovascular
      disease.

PMID- 9268964
TI  - Familial determinants of moderate and intense physical activity: a twin study.
AB  - This twin study estimates familial clustering of moderate and intense leisure
      time physical activity and investigates quantitatively its genetic and
      environmental components. Study subjects are 3,344 male twin pairs aged 33-51 yr.
      Moderate activity levels were assessed with six questions about discretionary
      walking or stair climbing for exercise. Five questions assessed regular
      participation in specific, intense athletic activities (running, bicycling,
      swimming, racquet, and other sports). Familial aggregation is estimated by odds
      ratio of one twin engaging in an activity when his co-twin does. Monozygotic and
      dizygotic twin correlations were compared to estimate genetic and nongenetic
      sources of phenotypic variation. For each activity, the familial aggregation odds
      ratio was statistically significant with values between 2.9 to 4.6 for intense
      activities and between 1.4 to 1.9 for all moderate activities but one.
      Monozygotic twin correlations were higher than dizygotic, suggesting genes play a
      role in the observed phenotypic variation. For four questions, and a compromise
      scale of moderate activity, the difference between correlations was statistically
      significant (P < 0.05). In this cohort, much of the phenotypic variability for
      both moderate and intense activities is a result of familial effects. Genes may
      influence regular participation in specific intense exercises more than moderate
      activity, such as walking for exercise.

PMID- 9268965
TI  - Impact shock and attenuation during in-line skating.
AB  - Although impact and shock attenuation associated with foot contact during running
      has been studied extensively, much less is known about these phenomena during in
      line skating (ILS). The purpose of this study was to describe these impact
      characteristics for ILS and to test the hypothesis that there is lower impact
      shock during ILS than in running at preferred velocities. Subjects ran and skated
      on a treadmill at preferred velocity, with low-mass accelerometers attached to
      both the distal tibia and head. Tibia and head acceleration data during stance
      were used to calculate peak acceleration (PA), peak frequency (PF), and median
      frequency (MedF). Impact attenuation (IA) between the tibia and head was
      quantified by comparison of PA values and by calculating a transfer function
      between the head and tibia frequency spectra. PA, PF, and MedF values were
      significantly lower in ILS than in running for both tibial and head data, whereas
      ILS was similar between the two movements. The ILS condition exhibited almost no
      power in the frequency range between 10 and 20 Hz, which has been associated with
      the foot impacting the ground. It is concluded that in-line skating results in
      less impact shock to the body with each foot contact, and may be a useful
      exercise modality for those wishing to reduce impact shock during aerobic
      training.

PMID- 9268966
TI  - Effects of exercise on appetite control: implications for energy balance.
AB  - At a time of increased obesity, decreased physical activity, and high food
      consumption, the relationship between physical activity and appetite control
      needs to be examined. Many people believe that the energy expended as a result of
      physical activity generates a drive to eat. However, a counterintuitive
      conclusion arises since there is no compelling evidence that increased physical
      activity increases energy intake. A suppression of hunger occurs following
      intense exercise; however, this effect is brief and has no influence on energy
      intake. Indeed, there does not appear to be any within-day effect of exercise on
      energy intake. Day-to-day effects of exercise on energy intake could occur, but
      only a few provocative data exist showing a delayed effect of exercise on energy
      intake 2 d later. Therefore, there appears to be only a weak short-term coupling
      between energy expenditure and energy intake. What about the effects of increased
      physical activity on food selection? The natural hypothesis would be that the
      energy reserves used during exercise would estimate a drive for a particular
      nutrient. There is no clear consistent evidence to indicate that in the short
      term, exercise induces changes in food or nutrient preferences. In the long-term
      there is some evidence that physical activity is associated with an increase in
      carbohydrate intake, but it is uncertain whether these changes are biologically
      driven for a result of changes of a psychological nature. Contrary to a popularly
      held view, food selection and nutrient intake constitute patterns of behavior
      held in place by environmental contingencies and short-acting post-ingestive
      physiological responses; these patterns of behavior are relatively immune to
      modulation by the metabolic effects of exercise.

PMID- 9268967
TI  - Physiological profiles of elite off-road and road cyclists.
AB  - There are minimal scientific data describing international caliber off-road
      cyclists (mountain bikers), particularly as they compare physiologically with
      international caliber road cyclists. Elite female (N = 10) and male (N = 10)
      athletes representing the United States National Off-Road Bicycle Association
      (NORBA) Cross-Country Team were compared with elite female (N = 10) and male (N =
      10) athletes representing the United States Cycling Federation (USCF) National
      Road Team. Submaximal and maximal exercise responses were evaluated during the
      "championship" phase of the training year when athletes were in peak condition.
      All physiological tests were conducted at 1860 m. Among the female athletes,
      physiological responses at lactate threshold (LT) and during maximal exercise
      (MAX) were similar between NORBA and USCF cyclists with two exceptions: 1) USCF
      cyclists demonstrated a significantly greater (P < 0.05) absolute (16%) and
      relative (10%) maximal aerobic power, and 2) MAX heart rate was significantly
      higher (P < 0.05) for the USCF athletes (6%). Among the male athletes,
      physiological responses at LT and MAX were similar between NORBA and USCF
      cyclists with two exceptions: 1) USCF cyclists produced significantly greater (P
      < 0.05) absolute (18%) and relative (16%) power at LT, and 2) USCF cyclists
      produced significantly greater (P < 0.05) absolute (12%) and relative (10%) power
      at MAX. These data suggest that, in general, elite off-road cyclists possess
      physiological profiles that are similar to elite road cyclists.

PMID- 9268968
TI  - Automated VO2max calibrator for open-circuit indirect calorimetry systems.
AB  - The complete calibration of indirect calorimetry systems involves simultaneous
      checks of gas analyzers, volume device, and software, and this requires a machine
      that can mimic accurately and precisely the ventilation and expired gases of an
      athlete. While previous calibrators have been built successfully, none have
      matched the ventilatory flows produced by athletes during high intensity
      exercise. A calibrator able to simulate high aerobic power (VO2max calibrator)
      was fabricated and tested against conventional indirect calorimetry systems that
      use chain-compensated gasometers to measure expired volume (VE systems) and
      calibrated electronic gas analyzers. The calibrator was also checked against a
      system that measures inspired volume (VI system) with a turbine ventilometer. The
      pooled data from both VE and VI systems for predicted VO2 ranging from 2.9 to 7.9
      L.min-1 and ventilation ranging from 89 to 246 L.min-1 how that the absolute
      accuracy (bias) of values measured by conventional indirect calorimetry systems
      compared with those predicted by the calibrator was excellent. The bias was < 35
      mL.min-1 for VO2 and carbon dioxide production, < 0.50 L.min-1 for ventilator (VE
      BTPS), -0.02% absolute for the percentage of expired O2 and +0.02% absolute for
      the percentage of expired CO2. Overall, the precision of the measured VO2, VCO2,
      and VE BTPS was approximately 1%. This VO2max calibrator is a versatile device
      that can be used for routine calibration of most indirect calorimetry systems
      that assess the ventilation and aerobic power of athletes.

PMID- 9268969
TI  - A model for optimizing cycling performance by varying power on hills and in wind.
AB  - The effect of varying power, while holding mean power constant, would have on
      cycling performance in hilly or windy conditions was analyzed. Performance for a
      70-kg cyclist on a 10-km time trial with alternating 1-km segments of uphill and
      downhill was modeled, with mean VO2 (3, 4, 5 L.min-1), variation in VO2 (5, 10,
      15%), and grade (0, 5, 10, 15%) used as independent variables. For the conditions
      of 4 L.min-1, 10% variation, and 10% grade, results were as follows: finishing
      time of 22:47.2 with varied power, versus 24:20.3 at constant power, for a time
      savings of 1 min 33.1 s. Separately, a 40-km time trial with alternating 5-km
      segments of headwind and tailwind (0, 8, 16, 24 km.h-1) was modeled, with the
      following results for the conditions of 4 L.min-1, 10% variation, and wind speed
      of 16 km.h-1: finishing time of 60:21.2 with power variation vs 60:50.2 at
      constant power, for a time savings of 29 s. Time saved was directly proportional
      to variation in VO2, grade, and wind speed and was indirectly proportional to
      mean VO2. In conclusion, the model predicts that significantly time savings could
      be realized on hilly and windy courses by slightly increasing power on uphill or
      headwind segments while compensating with reduced power on downhill or tailwind
      segments.

PMID- 9268970
TI  - The reproducibility of the Bruce protocol exercise test for the determination of
      aerobic capacity in older women.
AB  - The reproducibility of the Bruce exercise test protocol for the determination of
      maximal aerobic activity was evaluated in sedentary older women. Seventeen women
      between the ages of 51 and 68 yr performed five maximal graded exercise tests to
      volitional fatigue on a treadmill. VO2max (mL.kg-1.min-1) values averaged 27.5 +/
      1.1; 28.3 +/- 1.3; 28.4 +/- 1.3; 29.6 +/- 1.5; and 28.2 +/- 1.4 for trials 1-5,
      respectively, and were not significantly different. Criteria for a plateau in VO2
      at the point of exhaustion were met in 21 out of 85 tests (25%). The mean
      coefficient of variation VO2max for the subjects for the 5 tests was 6.5% (range,
      2.0-14%). Pearson's correlation coefficients for the study variables were
      significant, indicating good agreement between repeated tests (r2: between 0.70
      to 0.89). Although there were no significant differences among the mean VO2max
      values in the 5 trials, 11 subjects had a 1.0 ml.kg-1.min-1 or greater increase
      in the VO2max from test 1 to test 2, and only 6 subjects had no change or a
      decrease in VO2max. The mean difference between T2 and T3 was lower (T1 vs T2:
      0.8 mL.kg-1.min-1, T2 vs T3: 0.1 mL.kg-1.min-1) indicating slightly better
      agreement between the second and third set. Estimates of the between and within
      subject variance revealed a low within subject variance (4.2 (mL.kg-1.min-1)2)
      compared to the between subject variance (22.1 (mL.kg-1.min-1)2). This study
      demonstrates that a commonly used exercise testing protocol generates highly
      reproducible measurements of VO2max in women between 51 and 68 yr. The mean
      differences between tests and the high level of agreement between repeated tests
      suggests that a single measurement of VO2max can be performed to assess
      functional aerobic capacity in this population.

PMID- 9268971
TI  - Can we make low-fat foods more palatable?

PMID- 9268972
TI  - Practical tips for caring for HIV/AIDS patients.

PMID- 9268973
TI  - The role of exercise in the prevention and treatment of cancer.

PMID- 9268975
TI  - Pap smear refined.

PMID- 9268974
TI  - Will current clinical trials answer the most important questions about prostate
      adenocarcinoma?
AB  - Despite a heightened focus of the medical and research community on prostate
      cancer, many important questions about this disease remain unanswered. These
      include questions about the possible prevention of prostate cancer, as well as
      the optimal treatment approaches for localized, locally advanced, metastatic, and
      hormone-refractory disease. A whole host of prospective, well-designed clinical
      trials are currently in progress that should answer many of these questions. This
      review briefly explores some of these unresolved issues and describes ongoing
      trials designed to address them.

PMID- 9268976
TI  - The Prostate Cancer Intervention Versus Observation Trial (PIVOT).
AB  - The Prostate Cancer Intervention Versus Observation Trial (PIVOT) is a randomized
      trial designed to determine whether radical prostatectomy or expectant management
      provides superior length and quality of life for men with clinically localized
      prostate cancer. Conducted at Department of Veterans Affairs and National Cancer
      Institute medical centers, PIVOT will enroll over 1,000 individuals < 75 years of
      age. The primary study end point is all-cause mortality. Secondary outcomes
      include prostate cancer- and treatment-specific morbidity and mortality, health
      status, predictors of disease-specific outcomes, and cost-effectiveness. Within
      the first 3 years of enrollment, over 400 men have been randomized. Early
      analysis of participants' baseline characteristics indicate that enrollees are
      representative of men diagnosed with clinically localized prostate cancer
      throughout the United States. Therefore, results of PIVOT will be generalizable.
      These results are necessary in order to determine the preferred therapy for
      clinically localized prostate cancer.

PMID- 9268977
TI  - Clinical trials referral resource.

PMID- 9268978
TI  - Prostate cancer clinical trials of the Southwest Oncology Group.
AB  - The changing clinical dynamics of prostate cancer have resulted in a broadening
      of the research focus of the Genitourinary (GU) Cancer Committee of the Southwest
      Oncology Group (SWOG). Beginning with an emphasis on hormone-refractory disease
      in its early years, SWOG prostate cancer trials now cover the entire spectrum of
      the disease: localized, locally advanced, metastatic and hormone-refractory
      disease. As the world's largest GU cancer research group, the GU committee of
      SWOG has pioneered studies in combined androgen therapy for metastatic disease,
      quality-of-life (QOL) assessments for patients with localized and advanced
      disease, adjuvant therapy models, and prostate cancer chemoprevention. The
      committee has also formed the GU Global Group, whose purpose is to convene the
      chairs of the GU committees of all the major national and international oncology
      cooperative groups. Meeting semiannually, this group discusses activities within
      their respective organizations, plans collaborative strategies and protocols, and
      establishes global strategy in prostate cancer clinical research. The future
      directions of national and international prostate cancer trials will build on
      this broad foundation of well-conceived, logically sequenced studies.

PMID- 9268979
TI  - Imagery and hypnosis in the treatment of cancer patients.
AB  - Many patients with cancer often seek some means of connecting their mental
      activity with the unwelcome events occurring in their bodies, via techniques such
      as imagery and hypnosis. Hypnosis has been shown to be an effective method for
      controlling cancer pain. The techniques most often employed involve physical
      relaxation coupled with imagery that provides a substitute focus of attention for
      the painful sensation. Other related imagery techniques, such as guided imagery,
      involve attention to internally generated mental images without the formal use of
      hypnosis. The most well-known of these techniques involves the use of "positive
      mental images" of a strong army of white blood cells killing cancer cells.
      Despite claims to the contrary, no reliable evidence has shown that this
      technique affects disease progression or survival. Studies evaluating more
      broadly defined forms psychosocial support have come to conflicting conclusions
      about whether or not these interventions affect survival of cancer patients.
      However, 10-year follow-up of a randomized trial involving 86 women with cancer
      showed that a year of weekly "supportive/expressive" group therapy significantly
      increased survival duration and time from recurrence to death. This intervention
      encourages patients to express and deal with strong emotions and also focuses on
      clarifying doctor-patient communication. Numerous other studies suggest that
      suppression of negative affect, excessive conformity, severe stress, and lack of
      social support predict a poorer medical outcome from cancer. Thus, further
      investigation into the interaction between body and mind in coping with cancer is
      warranted.

PMID- 9268980
TI  - Society of Surgical Oncology Practice Guidelines. Laryngeal cancer surgical
      practice guidelines.

PMID- 9268981
TI  - Society of Surgical Oncology Practice Guidelines. Oropharyngeal and oral cavity
      cancer surgical practice guidelines.

PMID- 9268982
TI  - Society of Surgical Oncology Practice Guidelines. Parotid gland cancer surgical
      practice guidelines.

PMID- 9268983
TI  - Society of Surgical Oncology Practice Guidelines. Thyroid cancer surgical
      practice guidelines.

PMID- 9268985
TI  - Research helps shed light on role of apoptosis in tumor development and growth.

PMID- 9268984
TI  - PSA nadir levels after radiotherapy for prostate cancer: 'a powerful prognostic
      variable'.

PMID- 9268986
TI  - Distinct effects of various p53 mutants on differentiation and viability of human
      K562 leukemia cells.
AB  - Mutations of the p53 tumor suppressor are often observed in various human tumors,
      including blast crisis of chronic myelogenous leukemia (CML). The pattern of p53
      mutations in CML shows some peculiarities compared with majority of other
      malignancies. In particular, the substitutions at codon 273, one of the most
      common p53 alterations in various tumors, are not characteristic of CML. To test
      whether the distinctions in the pattern of p53 mutations are connected with some
      peculiarities of the biological effects of different mutant proteins in leukemic
      cells, we obtained and analyzed a panel of human K562 cell sublines expressing
      various exogenous p53; human Pro156, His175, His194, Trp248, and His273, or
      murine temperature-sensitive (ts) Val135 that has properties of mutant protein at
      37 degrees C, but shows activities of the wild-type (wt) p53 at 32 degrees C. We
      have found that expression of wt-p53 enhanced the dependence of cells on
      growth/survival factors. Incubation of sparse (< 10(5) cells per/ml) K562/Val135
      cultures at 32 degrees C caused apoptosis. In media conditioned by cells of
      different origin (K562, colorectal carcinoma LIM1215, Rat1 fibroblasts) the p53
      dependent apoptosis was inhibited. Under such conditions the expression of ts-wt
      p53 was accompanied by dramatic increase in the number of cells producing
      specific markers of erythroid differentiation-GlycPhA and Ag-Eb. Unlike to the wt
      p53, the majority of tumor-derived mutant p53 (Pro156, His175, His194) increased
      cell survival in low serum and decreased the number of cells expressing Glyc-PhA,
      CD9, CD15, and CD71 differentiation antigens. On the other hand, expression of
      His273-p53 caused significant augmentation in the number of CD9-positive cells
      and enhanced the dependence on growth/survival factors that are present in serum
      or conditioned media. The data obtained allow to suggest that an unusual pattern
      of p53 mutations in CML reflects some peculiarities of biological effects of
      certain mutant proteins on differentiation and viability of leukemic cells.

PMID- 9268987
TI  - Inhibition by 5-fluorouracil of ERCC1 and gamma-glutamylcysteine synthetase
      messenger RNA expression in a cisplatin-resistant HST-1 human squamous carcinoma
      cell line.
AB  - Pretreatment of 5-fluorouracil (5-FU), but not posttreatment, has been shown to
      augment the cytotoxicity of cisplatin (CDDP) or even circumvent CDDP resistance
      by inhibiting repair of platinum-DNA interstrand crosslinks as well as by
      reducing the cellular glutathione (GSH) contents in CDDP-resistant HST-1/CP0.2
      human squamous carcinoma cells. Because exogenous thymidine, which compensates
      for 5-FU-mediated inhibition of de novo DNA synthesis via salvage pathway, did
      not affect this schedule-dependent synergism, the modulatory effect of 5-FU on
      CDDP resistance would be attributed to the 5-FU-induced RNA damage. We therefore
      examined the effect of 5-FU on the steady-state levels of messenger RNA (mRNA) of
      a human excision repair gene ERCC1 and gamma-glutamylcysteine synthetase (gamma
      GCS) gene coding for a rate-limiting enzyme for GSH synthesis. The HST-1/ CP0.2
      cells were found to have significantly more mRNA expression of these respective
      genes than do parental HST-1 cells. In these cells, 5-FU pretreatment
      progressively inhibited mRNA expression of both ERCC1 and gamma-GCS after removal
      of 5-FU, without affecting glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA.
      A maximal mRNA suppression was observed at 48 h posttreatment. Such 5-FU-induced
      suppression of mRNA transcripts of these genes seems to be consistent with its
      inhibitory activity on DNA repair capacity and cellular GSH contents. In
      contrast, 5-FU did not reduce the level of glutathione-S-transferase-pi (GST-pi)
      or DNA topoisomerase 1 mRNA. Although not convinced, our data suggest that 5-FU,
      when incorporated into RNA, may inhibit both GSH synthesis and repair of platinum
      DNA adducts by downregulating the ERCC1 and gamma-GCS genes, thereby enhancing
      antitumor activity of CDDP and reversing resistance to CDDP in HST-1/CP0.2 cells.

PMID- 9268988
TI  - The sulfonic acid polymers PAMPS [poly(2-acrylamido-2-methyl-1-propanesulfonic
      acid)] and related analogues are highly potent inhibitors of angiogenesis.
AB  - The sulfonic acid polymers poly(2-acrylamido-2-methyl-1-propanesulfonic acid)
      (PAMPS), poly(4-styrenesulfonic acid) (PSS), and poly(anetholesulfonic acid)
      (PAS) proved to be highly potent inhibitors of angiogenesis in the chick
      chorioallantoic membrane (CAM) assay. PAMPS was found to achieve a dose-dependent
      inhibition of microvessel formation in the CAM assay ranging from 57 +/- 16%
      inhibition at 10 micrograms/disc to 72 +/- 15% at 150 micrograms/ disc. Also, PSS
      and PAS caused a strong inhibition of angiogenesis (55 +/- 19% and 48 +/- 16%,
      respectively, at 50 micrograms/disc), whereas poly(vinylsulfonic acid) (PVS) was
      found to be inactive at this dose. The compounds proved to be nontoxic for the
      developing chick embryo at these doses. Suramin, which was included as a
      reference compound, caused only a slight inhibition of vascular density, at a
      dose of 150 micrograms/disc, whereas pentosan polysulfate (PPS) was found to be
      toxic. PAMPS, PAS, and PSS, but not PVS, inhibited microvessel formation in the
      rat aorta-ring assay. In addition, the increased [3H-methyl]dThd uptake in
      endothelial cells in vitro upon stimulation with basic fibroblast growth factor
      (bFGF) was inhibited by PAMPS, PAS, and PSS at 20 micrograms/ml. A strong
      correlation (r = 0.95) was found between the antiangiogenic effect of the
      sulfonic acid polymers in the CAM assay and their inhibition of the bFGF-induced
      mitogenic response, indicating that bFGF is the target for these sulfonic acid
      polymers. These results suggest that sulfonic acid polymers, and in particular
      PAMPS, may be considered as specific, nontoxic angiogenesis inhibitors.

PMID- 9268989
TI  - Differential changes in genome structure and expression of the mdr gene family in
      multidrug-resistant murine erythroleukemia cell lines.
AB  - The genome structure and expression of mdr genes were examined in multidrug
      resistant sublines of two different murine (DBA/2J) Friend erythroleukemia cell
      lines, PC4 and C7D, derived by stepwise exposure to increasing concentrations of
      adriamycin beginning with 5 ng/ml. The PC4 cell lines selected in higher drug
      concentrations (80-1280 ng/ml) demonstrated amplification of all three mdr genes
      with preferential amplification of mdr3. Overexpression of the mdr2 and mdr3
      genes accompanied their genomic amplification; however, expression of mdr1 was
      not seen despite amplification. In the C7D cell lines selected with higher drug
      concentrations (40-160 ng/ ml), amplification and overexpression of mdr1 and mdr2
      without mdr3 was observed. Increased expression of mdr1 occurred prior to gene
      amplification. The distribution of mdr-specific genes in micrococcal nuclease
      generated chromatin fractions differing in transcriptionally active sequences and
      proteins was different between the parent and drug-resistant sublines. An
      enrichment (two- to threefold) of mdr3 genes in the H1-depleted mononucleosome
      fraction enriched for actively transcribed genes (e.g., globin) was detected by
      Southern analysis of chromatin fractions in PC4-80 cells (selected in 80 ng/ml of
      adriamycin and overexpressing mdr3), compared to the parental cells. mdr3
      enrichment was also detected using a new PCR-based method, which examined mdr3
      genes and repetitive sequences. Of note, the H1-depleted chromatin fraction from
      PC4-20 showed enrichment of the mdr3 gene, although mdr3 expression was not
      detected in the cell line. These studies showed a different pattern of gene
      amplification and overexpression in genetically related erythroleukemia cell
      lines selected for resistance to the same chemotherapeutic agent. A change in
      chromatin organization of mdr genes preceded overexpression and amplification of
      the mdr3 gene.

PMID- 9268990
TI  - Heterogeneous expression of DNA topoisomerase II alpha isoforms in tumor cell
      lines.
AB  - DNA topoisomerase II alpha is a nuclear enzyme essential for DNA metabolism and
      cell cycle progression. Previous studies have shown that human tumor cell lines
      can express more than one topoisomerase II alpha isoform through alternative
      splicing. A 160-kDa isoform of topoisomerase II alpha has been described in
      several cell lines selected for resistance to inhibitors of DNA topoisomerase,
      but its physiological function has not been defined. In the present study, we
      have identified two major (160 and 140 kDa) and two minor (150 and 145 kDa)
      isoforms of topoisomerase II alpha in drug-sensitive human leukemic CEM cells,
      all of which have lost C-terminal regions that produce epitopes recognized by
      specific antibodies. Reverse transcription-polymerase chain reaction and
      molecular cloning identified four alternatively spliced transcripts of
      topoisomerase II alpha from CEM cells. Furthermore, nucleotide sequencing
      indicated that the 160-kDa isoform is encoded by two transcripts derived from
      alternative splicing at a different C-terminal site and that the other two
      transcripts likely code for the 150-kDa isoform. Although the full-length
      topoisomerase II alpha resided in the cell nucleus, all altered isoforms, except
      the 160 kDa that was located in both cytoplasmic and nuclear extracts in about
      equal amount, were shown to be present predominantly in the cytosol. In contrast
      to the observations of other groups, we have not found an association of the
      topoisomerase II alpha isoforms with drug resistance. Rather, our results suggest
      that expression of topoisomerase II alpha isoforms is cell type specific or might
      be associated with the neoplastic phenotype of the cells. Thus, although T
      lineage tumor cell lines examined (CEM, Jurkat, and H9) displayed altered
      topoisomerase II alpha isoforms, normal T cells expressed only a full-length copy
      of the gene. Together, these results suggest that expression of altered
      topoisomerase II alpha isoforms is not limited to drug resistance, but might be a
      feature of neoplastic cells.

PMID- 9268991
TI  - Induction of proto-oncogenes during 3-deazaadenosine-stimulated differentiation
      of 3T3-L1 fibroblasts to adipocytes: mimicry of insulin action.
AB  - 3-Deazaadenosine (DZA) mimicked the molecular action of insulin in the induction
      of 3T3-L1 fibroblasts to differentiate into adipocytes. The molecular effects of
      DZA were compared with insulin, which served as a positive control, on the
      expression of proto-oncogenes during the initial stage of differentiation of 3T3
      L1 fibroblasts. Treatment of confluent 3T3-L1 fibroblasts with DZA or insulin
      produced a rapid but-transient expression of mRNA for proto-oncogenes c-fos and c
      jun within 30-60 min. The mRNA of c-myc increased for 2 h and then decreased 4 h
      after treatment. Electrophoretic mobility shift assays showed a heightened
      increase in the appearance of transcription factors AP-1 and AP-2. The increase
      was detectable as early as 1 h after the treatment with either DZA or insulin and
      was maintained for 6 h. 3T3-L1 cells stably transfected with the promotor of c
      fos linked to a CAT reporter gene showed an increase in CAT activity in response
      to DZA in a time- and dose-dependent manner. In cells stably transfected with
      antisense c-fos, neither DZA nor insulin was able to induce a differentiation
      response. The early transcription of c-fos, c-jun, and c-myc proto-oncogenes and
      the increased expression of transcription factors AP-1 and AP-2, induced by DZA
      and insulin, appear to be crucial events in the differentiation of the 3T3-L1
      fibroblasts to adipocytes.

PMID- 9268992
TI  - Perforating BB gun injuries of the globe.
AB  - BACKGROUND AND OBJECTIVE: To determine the visual and anatomic outcomes of eyes
      with perforating BB gun injuries. PATIENTS AND METHODS: The authors reviewed the
      surgical management and final visual outcome of seven patients with BB gun
      related perforating injuries of the globe seen by them between 1980 and 1995. Six
      patients underwent surgery, and one patient refused intervention and was lost to
      follow-up. Scleral buckles, lensectomies, and vitrectomies were performed in
      these six cases. RESULTS: Five patients had a final visual acuity of 5/200 or
      better, with four patients achieving 20/200 or better and two of them having
      20/70 or better. A posterior perforation involving the macula or an area temporal
      to the macula was associated with poor visual outcome. The visual acuity and the
      relative afferent pupillary defect at presentation or after the initial repair
      did not correlate with the final visual outcome. In addition, the presence of
      subretinal blood did not necessarily portend a poor prognosis in these young
      patients. CONCLUSIONS: At least some eyes with perforating injuries can retain
      good visual acuity with aggressive surgical management using modern vitrectomy
      techniques. Visual acuity should not necessarily be used as the only exclusion
      criterion for intervention or enucleation.

PMID- 9268993
TI  - Idiopathic macular hole following vitrectomy: implications for pathogenesis.
AB  - BACKGROUND AND OBJECTIVE: Attention to the pathogenesis and clinical features of
      macular hole formation has increased with the advent of therapy. The purpose of
      this study is to present three cases that occurred in atypical settings that may
      have important pathogenic implications. PATIENTS AND METHODS: The authors
      conducted a retrospective study of three patients who presented with macular
      holes that developed 10 months to 5.5 years after previous vitrectomy. In each
      case, the cortical vitreous layer was absent in the region of the macula at the
      time of operation for the macular hole. RESULTS: The macular hole was
      successfully sealed and the visual acuity improved in all patients. All three
      cases in this report lacked an operculum, occurred long after vitreous removal,
      and had no evidence of any residual cortical vitreous. CONCLUSIONS: Macular hole
      formation in the absence of cortical vitreous suggests the possibility that the
      etiology of macular holes may involve a spontaneous umbo dehiscence rather than
      vitreous-induced surface traction. A mechanism involving a cystic degenerative
      process is proposed as the cause of atypical and typical macular hole formation.

PMID- 9268994
TI  - A case-control study of suprachoroidal hemorrhage during pars plana vitrectomy.
AB  - BACKGROUND AND OBJECTIVE: To investigate the risk factors associated with
      suprachoroidal hemorrhage (SCH) during vitrectomy. PATIENTS AND METHODS: Of 6971
      pars plana vitrectomies performed between May 1988 and December 1994, SCH
      occurred intraoperatively in 12 (0.17%) cases. Forty-two age- and sex-matched
      control subjects were selected by computer-generated random numbers. Preoperative
      and intraoperative variables were subjected to univariate and conditional
      logistic regression analysis. RESULTS: Statistically significant risk factors for
      SCH after univariate analysis included myopia (P = .048), aphakia or pseudophakia
      (P = .024), rhegmatogenous retinal detachment (P = .044), scleral buckling and/or
      encirclage at vitrectomy (P = .029), and longer duration of surgery (P = .044).
      Multivariate analysis revealed independent risks associated with the absence of a
      lens and longer duration of the surgery. CONCLUSION: A knowledge of the risk
      factors involved with SCH helps the physician to identify patients who are at a
      greater risk for this complication.

PMID- 9268995
TI  - Combined subretinal and sub-retinal pigment epithelium neovascular membranes in
      age-related macular degeneration: a clinicopathologic study of six cases.
AB  - BACKGROUND AND OBJECTIVE: Subfoveal neovascular membranes are usually located
      either in the subsensory retinal space or below the retinal pigment epithelium
      (RPE). This article describes the clinical and histopathologic features of
      subfoveal membranes with both subretinal and sub-RPE components (combined
      membranes). PATIENTS AND METHODS: Six surgically excised subfoveal neovascular
      membranes from six patients were examined histopathologically. Preoperative and
      postoperative clinical information was obtained from each patient. RESULTS:
      Clinically, the combined membranes had no special characteristic features. The
      most common fluorescein angiographic finding postoperatively was a window defect
      of the RPE. Visual acuity improved in three patients and became worse in the
      other three patients. CONCLUSIONS: All patients with combined subfoveal
      neovascular membranes had age-related macular degeneration. In this disease, a
      single subfoveal membrane may extend into both the subretinal and the sub-RPE
      spaces. Patients may benefit from surgical removal of the membrane.

PMID- 9268996
TI  - Anticardiolipin antibodies and retinal vascular complications in Behcet's
      disease.
AB  - BACKGROUND AND OBJECTIVE: Intravascular thrombosis is a well-recognized feature
      of Behcet's disease (BD). In this study, the existence of a connection between
      serum anticardiolipin (aCL) antibodies and retinal vascular complications in BD
      is investigated. PATIENTS AND METHODS: Serum aCL antibody levels were quantified
      in 31 patients with BD, all of whom fulfilled the major criteria of the disease.
      Patients were evaluated in terms of retinal vascular complications. Serum aCL
      antibody levels were determined through the ELISA method. Statistical analysis
      was performed with the chi-squared test and the Fisher exact test. RESULTS: Of 12
      patients with high aCL antibody levels, retinal vascular thrombosis was detected
      in 5 and retinal vasculitis was present in 8. However, there was no statistically
      significant relation between these complications and serum aCL antibody elevation
      (P > .05). CONCLUSION: Based on this series of 31 patients with BD, there does
      not seem to be a significant correlation between retinal vascular complications
      and serum aCL antibody levels.

PMID- 9268997
TI  - Intraocular pressure increments after cataract extraction in glaucomatous eyes
      with functioning filtering blebs.
AB  - BACKGROUND AND OBJECTIVE: The effects of cataract extraction on intraocular
      pressure (IOP) were studied in glaucoma patients who had previously undergone
      trabeculectomy. PATIENTS AND METHODS: The files of 22 patients with 25
      glaucomatous eyes with functioning filtering blebs who underwent cataract
      extraction were retrospectively reviewed. All patients had undergone
      pretrabeculectomy examination and had at least 18 months of follow-up after
      cataract surgery. Visual acuity, IOP, status of the filtering bleb, and the
      number of medications applied were recorded. RESULTS: The mean increase in IOP
      was 3.63 mm Hg, 3.84 mm Hg, 5.4 mm Hg, and 2.8 mm Hg at 3, 6, 12, and 18 months
      after cataract extraction, respectively. This elevation was statistically
      significant 3 months postoperatively (P < .001) and remained relatively constant
      thereafter. The postoperative IOP was still significantly lower than the
      pretrabeculectomy IOP (P < .001). CONCLUSIONS: Cataract extraction through
      corneal incisions in patients with functioning filtering blebs is followed by an
      increase in IOP. Cataract surgery in these patients does not neutralize the
      pressure-lowering effect achieved by the trabeculectomy, but it tends to elevate
      the post-trabeculectomy baseline pressure.

PMID- 9268998
TI  - Topical mitomycin-C for pterygia: is single application appropriate?
AB  - BACKGROUND AND OBJECTIVE: Mitomycin-C has been shown to dramatically reduce
      pterygium recurrence rates; however, its use has been associated with serious
      complications, especially in higher cumulative doses. The authors investigated
      the safety and efficacy of progressively reducing dosages of mitomycin-C as an
      adjunct to pterygium surgery. PATIENTS AND METHODS: Four hundred eighty-one
      consecutive primary and recurrent pterygia were surgically excised in a
      prospective nonrandomized trial using five different mitomycin-C dosages.
      Recurrence was defined as fibrovascular tissue over the corneoscleral limbus onto
      clear cornea in the area of previous pterygium excision. RESULTS: Seventy-seven
      patients in a control group without mitomycin-C had a recurrence rate of 65% with
      a mean follow-up of 33 months. A group of 77 patients treated with 0.4 mg/ml of
      mitomycin-C, four times per day for 2 weeks, had a recurrence rate of 2.5% with 6
      (10%) serious complications (mean follow-up 34 months). A group of 22 patients
      treated with 0.2 mg/ml of mitomycin-C, four times per day for 10 days, had a
      recurrence rate of 55% with 3 (7.3%) non-vision-threatening complications (mean
      follow-up 32 months). A group of 16 patients treated with 0.2 mg/ml of mitomycin
      C intraoperatively for 3 minutes without conjunctival closure had a recurrence
      rate of 44% with no complications (mean follow-up 35 months). Finally, a group of
      289 patients treated with 0.2 mg/ml of mitomycin-C intraoperatively for 3 minutes
      with conjunctival closure had a recurrence rate of 2.7% and no complications
      (mean follow-up 26 months). CONCLUSION: Although the authors' results with single
      application are encouraging, the use of mitomycin for pterygia remains
      controversial. The biologic potency of this agent, the duration of its action,
      and the dearth of large-scale controlled, randomized trials demand cautious
      individual judgment by the surgeon when considering the use of this potent drug.

PMID- 9268999
TI  - Epiretinal fibrosis.

PMID- 9269000
TI  - Nasal reconstruction combined with dacryocystorhinostomy in a patient with
      absence of half of the nose.
AB  - This article describes a rare case of unilateral arhinia (congenital absence of
      half of the nose), in which total nasal reconstruction was performed. A glass
      Jones tube was used to create a new nasolacrimal duct connecting the lumen of the
      existing lacrimal sac to the contralateral normal nasal cavity.

PMID- 9269002
TI  - Aspirating specula with sponge covers.
AB  - Improved aspirating specula for the removal of irrigating fluid during ocular
      surgery are now commercially available. Thin sponge covers are used to prevent
      the conjunctiva from occluding the aspiration ports, thereby ensuring continuous
      effective suction.

PMID- 9269001
TI  - Chalazion-induced hyperopia as a cause of decreased vision.
AB  - This article presents three cases of decreased vision due to acquired hyperopia,
      which were caused by a chalazion of the upper eyelid. Through manifest refraction
      and computerized corneal topographic analysis, acquired hyperopia associated with
      central corneal flattening was revealed. These findings were responsible for the
      blurred vision that was reversed by chalazion resolution or removal. Although not
      usually considered a risk factor for refractive disorders other than astigmatism,
      chalazia of the upper eyelid can present as a decrease in vision associated with
      reversible central corneal flattening and acquired hyperopia.

PMID- 9269003
TI  - A method of drop administration.
AB  - Self-administering drops can be a daunting task for many patients. The authors
      describe a method of drop administration that allows a patient to accurately
      place drops without the need for special devices or touching the eye. With the
      bottle of drops held upside down, the back of the thumb is rested on the forehead
      to stabilize the bottle. The bottle tip can be seen over the eye. The other hand
      retracts the inferior lid to catch the drop. Poor compliance is common and is
      often caused by difficulties with drop administration. This simple technique may
      improve compliance.

PMID- 9269004
TI  - Argon laser photocoagulation in the treatment of the palpebral lobe cysts of the
      lacrimal gland (dacryops).
AB  - Dacryops is a closed cyst that develops on the palpebral lobe of the lacrimal
      gland, manifesting in the region of the external canthus. Its slow and insidious
      growth causes mechanical and aesthetic problems that do not regress
      spontaneously. Treatment involves excision of the cyst while sparing the adjacent
      glandular tissues. In cases associated with hypolacrimation, marsupialization of
      the cyst is indicated. To obtain a reduction of the cyst to an aesthetically
      acceptable level in cases of simple dacryops, the authors suggest argon laser
      therapy, which avoids the risks related to surgery and general anesthesia and
      eliminates the need for hospitalization. Two patients with simple dacryops were
      treated with blue-green argon laser under local anesthesia. At the end of follow
      up, the cysts had been clinically reduced in volume and were not visible by
      external examination. In cases of simple dacryops, laser therapy is suitable for
      the reduction of the cyst. Photocoagulation treatment is not advisable in cases
      that are complicated by fistulas or where the clinical presentation is atypical.

PMID- 9269005
TI  - Evaluation of visual function following argon laser photocoagulation in central
      serous retinopathy.
AB  - The authors of previous studies on the role of photocoagulation for central
      serous chorioretinopathy (CSR) have based their deductions on the premise that a
      Snellen visual acuity of 6/6 is the end point of recovery. It is now known that
      patients with a visual acuity of 6/6 may have defective contrast sensitivity
      indicative of a visual function deficit. The present study was a prospective,
      controlled, and randomized evaluation of patients suffering from their first
      attack of CSR, in which contrast sensitivity was used to determine the
      effectiveness of argon laser photocoagulation as compared with more conservative
      treatment. Although long-term studies are necessary, the results of this study
      showed that while photocoagulation increases the rate of recovery for visual
      acuity, it is also linked with significant loss and slower recovery of contrast
      sensitivity.

PMID- 9269006
TI  - A proposal for reclassification of oral candidosis.

PMID- 9269007
TI  - Oral endotoxin in healthy adults.

PMID- 9269008
TI  - Residual cysts.

PMID- 9269009
TI  - Mass in the infratemporal fossa.

PMID- 9269010
TI  - Comparison of sublingually and orally administered triazolam for premedication
      before oral surgery.
AB  - OBJECTIVES: This study evaluated sublingual administration of triazolam for
      preoperative sedation in dental outpatients. STUDY DESIGN: A double-blind,
      placebo-controlled study compared 0.25 mg sublingual triazolam, 0.25 mg oral
      triazolam, and placebo administered 1 hour before oral surgery. RESULTS:
      Sublingual triazolam resulted in significantly less anxiety and pain at 15
      minutes intraoperatively than both oral triazolam and placebo (p < 0.05).
      Patients' global evaluation of the efficacy of sedation ranked sublingual
      triazolam as significantly more efficacious than placebo (p < 0.05) with oral
      triazolam intermediate between the two. No difference was demonstrated in the
      rate of recovery or incidence of side effects between the two drug groups. Plasma
      triazolam levels were higher after sublingual administration during and after the
      surgical procedure. CONCLUSIONS: These results indicate that sublingual triazolam
      results in greater anxiolytic activity and less pain perception than oral
      administration as a result of greater plasma drug levels and may be useful as an
      alternative for nonparenteral outpatient sedation.

PMID- 9269011
TI  - A comparison of cardiac rate-pressure product and pressure-rate quotient with
      Holter monitoring in patients with hypertension and cardiovascular disease: a
      follow-up report.
AB  - OBJECTIVES: The purpose of this study was to evaluate patients with hypertension
      or cardiovascular disease, or both, for myocardial ischemia and cardiac
      arrhythmias while undergoing minor oral surgery. STUDY DESIGN: Sixteen patients
      were studied with noninvasive monitoring including heart rate, systolic,
      diastolic, and mean arterial blood pressure to calculate rate-pressure product
      (systolic blood pressure multiplied by heart rate) and pressure-rate quotient
      (mean arterial pressure divided by heart rate). These calculated measures were
      compared with the incidence of cardiac arrhythmias and ST segment depression
      recorded on a continuous Holter monitoring system. RESULTS: Nine of 16 (56%)
      developed supraventricular or ventricular ectopy during dental extractions or
      minor preprosthetic surgery performed with local anesthesia 2% xylocaine with
      1/100,000 epinephrine dilution. Three of the nine patients who experienced these
      arrhythmias had coincident abnormal rate pressure product and pressure-rate
      quotient values. None of these patients exhibited ST-T wave changes suggestive of
      myocardial ischemia. Atrial or ventricular ectopy suggests that myocardial
      irritability was more likely to occur than ischemia as measured by Holter
      monitoring and compared with abnormal rate pressure product and pressure-rate
      quotient values recorded.

PMID- 9269012
TI  - Photoelastic analysis of miniplate osteosynthesis for mandibular angle fractures.
AB  - OBJECTIVE: The purpose of this study was to reassess Champy's findings, which
      were instrumental in justifying the theory of tension band plating for mandibular
      angle fractures. STUDY DESIGN: Ten anatomically correct mandibles were fabricated
      with a photoelastic resin. In five mandibles, angle fractures were created and
      fixed with a superior border miniplate; five uncut mandibles served as controls.
      Each mandible was loaded in a manner that simulated physiologic conditions. The
      internal stress patterns were preserved within the models by completing a stress
      freezing cycle. RESULTS: The stress patterns in the experimental mandibles
      virtually replicated the patterns seen in the controls. Stress fringes were
      present surrounding the outer screws, indicating that these screws were subjected
      to pull-out forces. CONCLUSIONS: There is greater force on the outer screws that
      may contribute to fixation failure. The theory of tension band plating for
      mandibular angle fractures is accurate but Champy's model is oversimplified.

PMID- 9269013
TI  - Clinical evaluation of hydroxyapatite-coated titanium plasma-sprayed and titanium
      plasma-sprayed cylinder dental implants: a preliminary report.
AB  - OBJECTIVE: The purpose of this article was to present the preliminary results of
      a prospective clinical trial comparing titanium plasma-sprayed versus
      hydroxyapatite-coated titanium plasma-sprayed cylinder (press fit) implants in
      different regions of the mouth. STUDY DESIGN: Sixty-five subjects met the
      inclusion requirements. Surgery was done in two phases by four experienced
      surgeons. Implant placement and abutment connection were separated by 3 to 4
      months in the mandible, 6 to 7 months in the maxilla. Patients were assigned to
      either titanium plasma-sprayed or hydroxyapatite-coated implants on the day of
      surgery. Implant placement was not stratified for the region of the jaws. Outcome
      assessment was failure (loss) of an implant before or within 3 months of second
      phase surgery. RESULTS: Three hundred fifty-two implants equally distributed
      between titanium plasma-sprayed and hydroxyapatite-coated titanium plasma-sprayed
      implants were placed in four different sites; anterior maxilla, posterior
      maxilla, anterior mandible, and posterior mandible. There were a total of 15
      failures (4.26%). Overall, titanium plasma-sprayed implants showed a higher but
      not significant failure rate compared with hydroxyapatite-coated implants (p =
      0.06). Although not statistically significant, we believe that a smoking history
      played an important role in the failure of implants. CONCLUSION: This study
      suggests that an hydroxyapatite-coating of an implant allows superior initial
      integration when compared with a titanium plasma-sprayed surface.

PMID- 9269014
TI  - HIV-associated oral pleomorphic B-cell malignant lymphoma.
AB  - A 48-year-old HIV-seropositive homosexual patient presented with an ulcerative
      lesion in the left side of the soft palate, extensively involving local soft
      tissue structures. On histologic evaluation the lesions appeared to be a large
      cell high-grade B-cell pleomorphic lymphoma with anaplastic and plasmacytoid
      features harboring Epstein-Barr virus genome in the tumor cells. Although known
      to be associated with HIV infection, this is a rare subtype of a malignant
      lymphoma arising in a patient positive for HIV. Its meaning is yet unknown in
      biologic and prognostic terms.

PMID- 9269015
TI  - Cavernous hemangioma in the submandibular gland masquerading as sialadenitis:
      case report.
AB  - This report describes a case of cavernous hemangioma in the submandibular gland
      of a 37-year-old Irish woman. The lesion clinically and radiologically (as shown
      both by plain radiographs and computed tomography imaging) resembled salivary
      calculous disease. Numerous phleboliths were present in the hemangioma. The
      rarity of a cavernous hemangioma in such a location and its simulation of
      salivary calculous disease stimulated us to report the case.

PMID- 9269016
TI  - Candidal colonization and oral candidiasis in patients undergoing oral and
      pharyngeal radiation therapy.
AB  - OBJECTIVES: Radiotherapy-induced hyposalivation encourages oral candidal
      colonization that often leads to oral/pharyngeal candidiasis. The purpose of this
      study was to quantitate oral candidal colonization, assess signs, symptoms, and
      response to antifungal management, speciate Candida, and evaluate the influence
      of smoking and dentures. STUDY DESIGN: Forty-six patients undergoing radiation
      therapy for oral/pharyngeal squamous cell carcinoma were evaluated clinically and
      by Candidal cultures before, during, and after irradiation. RESULTS: All patients
      complained of progressive xerostomia. There was a significant increase in the
      prevalence of positive candidal cultures (P = < 0.0001): baseline 43%, completion
      of radiotherapy 62%, and follow-up timepoint 75%. Smoking and denture wearing
      were not statistically significant risk factors for increased candidal
      colonization (p = 0.085 and p = 0.420, respectively). Eight patients developed
      clinical candidiasis. Although five responded clinically to systemic antifungal
      medication, all follow-up cultures remained positive. Candida albicans was the
      predominant species at baseline and completion of radiation (85% and 68%,
      respectively). CONCLUSIONS: When salivary glands are included in the field of
      radiation, xerostomia occurs, causing progressive increases in oral Candida
      colonization. Because 17.4% developed clinical candidiasis during radiotherapy
      and the question of fungal resistance remains speculative, a recommendation for
      the prophylactic use of antifungal medication is unresolved.

PMID- 9269017
TI  - Proliferative verrucous leukoplakia: a follow-up study of 54 cases.
AB  - OBJECTIVES: Proliferative verrucous leukoplakia is a unique form of oral
      leukoplakia that has a high risk for becoming dysplastic and transforming into
      squamous cell carcinoma. The purpose of this review is to update patient
      profiles, pathogenesis, and survival. STUDY DESIGN: Fifty-four patients with
      proliferative verrucous leukoplakia (17 from a previous report) were followed
      prospectively in our clinic for a mean of 11.6 years after initial biopsy.
      RESULTS: In the patient population studied, the mean age was 62 years, and women
      outnumbered men 4 to 1. Multiple intraoral sites were involved (mean, 2.6 per
      patient); the most common sites were buccal mucosa in women and tongue in men. In
      a mean time of 7.7 years, 70.3% of the patients developed a squamous cell
      carcinoma at a proliferative verrucous leukoplakia site, most frequently the
      gingiva and tongue. Twenty-one of the patients with proliferative verrucous
      leukoplakia died of proliferative verrucous leukoplakia-associated carcinoma.
      Only 31% of the 54 patients used tobacco in any form. Radiation did not appear to
      enhance surgical control. CONCLUSIONS: Proliferative verrucous leukoplakia is a
      high risk precancerous lesion with a high mortality rate. Because of both the
      propensity for progression to dysplasia and malignancy, as well as a high
      recurrence rate, these patients must be treated aggressively and followed
      carefully.

PMID- 9269018
TI  - Lichen sclerosus et atrophicus of the oral cavity: report of two cases.
AB  - Lichen sclerosus et atrophicus is a depigmenting mucocutaneous disease most
      frequently affecting the female genitalia. Genital lesions are symptomatic and
      may be functionally debilitating. Oral lesions are of little significance other
      than the esthetic concerns of perioral lesions. In view of the rarity of reported
      cases, one lesion of the labial mucocutaneous area and a second of the palate are
      presented along with a description of the disease's clinical and histopathologic
      findings and a brief review of the literature. The lip lesion was partially
      resolved with topical corticosteroids and was then fully eliminated with topical
      testosterone. Histologic verification and examination for the simultaneous
      occurrence or absence of oral and the more common genital-cutaneous lesions is
      essential if meaningful information in the medical-dental literature is to be
      obtained in the future.

PMID- 9269019
TI  - Gingival squamous cell carcinoma in a patient with chronic graft-versus-host
      disease.
AB  - This article describes a gingival squamous cell carcinoma that developed in a 21
      year-old woman who received a bone marrow transplant at the age of 16 from her
      human leukocyte antigen-identical sister as treatment for severe aplastic anemia.
      Thirty days after transplantation, she presented with cutaneous erythema as a
      result of acute graft-versus-host disease, and this subsequently evolved into
      chronic graft-versus-host disease. A lichenoid white plaque of the gingiva
      developed shortly thereafter, and it began to increase in size rapidly 4 years
      posttransplantation. Biopsy indicated squamous cell carcinoma arising in this
      region, apparently associated with chronic graft-versus-host disease. Few reports
      have described a secondary solid malignancy involving the oral cavity of young
      adults after bone marrow transplantation.

PMID- 9269020
TI  - Oral lichen planus is not associated with IgG circulating antibodies to
      epithelial antigens.
AB  - Autoantibodies to a number of epithelial components have previously been
      described in small groups of patients with lichen planus. Recently a group of
      antibodies to monkey esophagus have been detected in lichen planus related to
      hepatitis C virus infection. This study has examined the frequency of serum
      antiepithelial antibodies in a group of patients with idiopathic oral lichen
      planus and lichenoid drug reactions. Five of 34 patients with idiopathic lichen
      planus and two of six patients with lichenoid eruptions had circulating
      antibodies that gave rise to an antinuclear pattern when examined using
      epithelial tissue. However, these antibodies were present in only low titer and
      were not specific to a particular clinical presentation of lichen planus or
      lichenoid drug reaction. It seems likely therefore that such antibodies do not
      play an important part in the etiopathogenesis of lichen planus, and their
      detection is unlikely to be beneficial in the diagnosis of this disease.

PMID- 9269021
TI  - Oral pemphigus: clinical significance of esophageal involvement: report of eight
      cases.
AB  - The extension of the blisters of pemphigus to the esophagus is relatively
      uncommon, especially in patients treated with corticosteroids who appear to be in
      clinical remission. The aim of this study was to evaluate the esophagus in eight
      patients affected by oral pemphigus in various stages of the disease. Upper
      gastrointestinal endoscopy revealed esophageal involvement in five patients (two
      men and three women); three had blisters or erosions in the upper esophagus,
      whereas two showed red longitudinal lines along the entire organ. Direct
      immunofluorescence was positive in all eight patients. It is suggested that
      endoscopic examination of esophageal mucosa is an objective criterion by which to
      judge the success of therapy of pemphigus vulgaris.

PMID- 9269022
TI  - Healing potential of osteotomies of the nasal sinus in the dog.
AB  - Maxillary sinus osteotomy is indicated for transantral surgical approaches to
      palatal roots of maxillary teeth. There are no reports on the healing potential
      of such defects. OBJECTIVES: To determine by histologic examination, the
      reparative process of the nasal cavity of dogs after small and large perforations
      with and without a resorbable collagen membrane. STUDY DESIGN: Five mm and 6 x 12
      mm diameter osteotomies were created through the maxilla of 12 beagle dogs.
      Resorbable collagen membranes were placed over defects on six dogs. After 5
      months, sections of the defects were histologically evaluated. RESULTS:
      Examination revealed partial osseous healing with presence of central areas of
      fibrous scar tissue in all samples. Defects covered with the resorbable collagen
      membranes showed no improvement in osseous regeneration. CONCLUSION: Based on our
      results, defects (regardless of their size) tend to repair with limited bony
      covering and fibrous scar. Furthermore, resorbable collagen membranes do not
      improve osseous repair.

PMID- 9269023
TI  - Linear tomography's clinical accuracy and validity for presurgical dental implant
      analysis.
AB  - Accurate assessment of alveolar ridge morphology and inferior alveolar canal
      location is critical in the presurgical planning phase for dental implant
      therapy. This study examined the accuracy and validity of linear tomography in
      the presurgical assessment of potential mandibular implant sites. Seven subjects
      (six oral and maxillofacial surgeons and one oral radiologist) traced the
      mandibular cortical bone and inferior alveolar canal on linear tomographic images
      taken from five mandibles on five separate occasions over 5 weeks. Tracings and
      the sectioned mandibles were scanned into a computer and assessed for eight
      measurement criteria. Statistically significant findings were present for
      intraobserver variability, interobserver variability, and differences between the
      perceived and actual anatomic structures within the assessed plane of section.
      These findings demonstrate that the inherent dimensional instability of linear
      tomography severely limits its diagnostic and clinical role in preoperative
      implant site assessment.

PMID- 9269024
TI  - In vivo study of approximal caries depth on storage phosphor plate images
      compared with dental x-ray film.
AB  - The aim of this in vivo study was to compare approximal caries depth on storage
      phosphor plate images to conventional film. A Soredex Digora imaging plate was
      placed in a film bite-wing positioner behind a Kodak Ektaspeed Plus film package
      without lead foil. The effect of scattered radiation on film without lead foil
      with a storage phosphor plate at the back was studied in a separate in vitro
      experiment. Compared with film protected by lead foil, the film showed higher
      density, but comparable contrast. For the in vivo study, clinical bite-wing
      exposures were made with the setup described above, with exposure settings for
      Ektaspeed Plus film. A four-point scale was chosen for approximal caries depth: 0
      = no caries; 1 = caries in enamel; 2 = caries reaching dentino-enamel junction; 3
      = caries into dentin. The bite-wing film images were shown to a panel of four
      experts. Sixty surfaces were selected for observer performance, based on
      identical scorings of the experts consensus classification. Next, six dentists
      evaluated both film and storage phosphor plate images with the same four point
      scale. Analysis of variance revealed a significant observer and image modality
      effect without an interaction effect. In conclusion, caries depth on storage
      phosphor plate images was underestimated compared with film-based images.

PMID- 9269025
TI  - TACT imaging of primary caries.
AB  - OBJECTIVE: Tuned-aperture computed tomography, a new method for creating 3-D
      radiographic information based on optical aperture theory, was evaluated for
      diagnostic efficacy in primary caries detection. STUDY DESIGN: Sixty-four
      extracted teeth with 89 carious lesions were imaged with D-speed film, direct
      digital, and TACT modalities. A commercially available, 8-bit, charge-coupled
      device was used in the later two modalities. Six trained observers were asked to
      identify the presence or absence and depth of interproximal and occlusal lesions
      for all three modalities. The teeth were sectioned and examined microscopically
      to determine ground truth. Logistic regression analysis was performed for all
      three imaging systems for the detection task. Analysis of variance was used for
      depth determination. Detection of lesion, depth of lesion accuracy, and time for
      diagnosis were also examined. RESULTS: For caries detection TACT and film were
      not different (p = 0.2216) with the Wald statistic. Film and TACT were
      significantly more accurate than the digital system (p = 0.0001). Scheffe's post
      hoc test revealed that TACT and film were more accurate than the direct digital
      system for determining lesion depth (p = 0.05) but not statistically different
      when compared with each other. The detection data were substantiated further by
      receiver operating characteristic analysis that demonstrated similar statistical
      relationships. Time required per diagnosis was not shown to be statistically
      different among the three imaging modalities. CONCLUSIONS: We conclude for caries
      detection and depth determination that TACT could not be distinguished from film
      despite the significant relative loss of information capacity in the charge
      coupled device receptor. The relatively poorer performance yielded by the digital
      control images suggests that increased information capacity associated with more
      modern charge-coupled device detectors may improve diagnostic performance for
      both direct digital and TACT displays over that demonstrated in this
      investigation.

PMID- 9269026
TI  - Chickenpox complications among immunocompetent hospitalized children in Italy.
      Acyclovir-Chickenpox Italian Study Group.
AB  - OBJECTIVE: To evaluate the frequency and clinical spectrum of chickenpox
      complications among immunocompetent hospitalized children. PATIENTS AND METHODS:
      Multicentre retrospective study of clinical records of all patients consecutively
      hospitalized for varicella during the last decade, in ten tertiary care clinical
      centres of Pediatrics and Infectious Diseases, throughout Italy. RESULTS: Two
      hundred and nineteen out of 991 patients (22.1%) hospitalized for varicella
      suffered from a complicated disease (247 complicating events on the whole).
      Central nervous system (CNS) involvement was prevalent (104 episodes), followed
      by skin/soft tissue infections, lower respiratory tract involvement, and
      thrombocytopenia. A complicated disease was significantly associated with the
      male gender and an elevated incidence of varicella-zoster (VZ) virus infection
      acquired by household contacts. The involvement of lower respiratory airways and
      skin/soft tissues seemed to occur at an earlier age, compared with CNS and
      thrombocytopenia. Moreover, lower respiratory tract and skin/soft tissue
      infections occurred earlier during disease course than complications interesting
      the CNS and coagulation system. All subjects with complicated chickenpox showed a
      favourable outcome within 5-40 days, except two patients developing a lethal
      cardiomyopathy and Reye syndrome, respectively. Anyway, chickenpox complications
      led to a prolonged hospitalization, and needed further pharmacologic treatment in
      all evaluated cases. The administration of anti-VZ virus treatments (i.v.
      acyclovir or VZ immunoglobulins) did not modify significantly the course of
      disease in treated patients, when compared with untreated ones. CONCLUSIONS:
      Although chickenpox is considered a self-limiting, uncomplicated disease in
      immunocompetent children, when assessing hospitalized patients a considerable
      incidence and a broad spectrum of complications are observed, requiring prolonged
      admission and pharmacologic and supportive care. Even though a lethal outcome
      remains a rare occurrence, it may be of relevant concern when considering the
      overall incidence of chickenpox in the general population. The role of an early
      antiviral treatment in reducing the incidence and severity of varicella
      complications deserves further evaluation.

PMID- 9269027
TI  - Solitary hepatocellular adenoma in infancy.
AB  - Here is presented an exceptional case of liver cell adenoma in a five-year-old
      child. The neoplasm was diagnosed when the child was taken to hospital in a state
      of shock and coma because of the contemporary laceration of the neoplasm and of
      the spleen in consequence of a causal falling. The neoplasm is histologically
      defined, possible clinical pictures are described as well as the differential
      diagnosis and the tests useful for the diagnosis.

PMID- 9269028
TI  - Influence of graft versus host reaction on the T cell repertoire differentiating
      from bone marrow precursors following allogeneic bone marrow transplantation.
AB  - When lethally irradiated AKR (Mls-1a) mice were reconstituted with bone marrow
      (BM) cells plus a small number (0.5%) of mature T cells from allogeneic B10.AQR
      or B10 (Mls-1b) mice and minor GVHR was induced in the recipients, almost
      complete donor chimerism was accomplished in the early stages after
      reconstitution. By contrast, in irradiated AKR mice reconstituted with T cell
      depleted BM cells alone from B10 or B10.AQR mice, radio-resistant T cells of
      recipient origin persisted for a relatively long period in peripheral lymphoid
      tissues. In this paper the influence of residual T cells in the chimeric mice on
      generation of the T cell repertoire derived from donor BM is discussed. It will
      be demonstrated that the recipient (AKR) T cells are capable of producing Mls-1a
      antigens (Ag) after lethal irradiation in vivo. These recipient T cells
      eventually induce clonal elimination of Mls-1a reactive V beta 6+, V beta 8.1+
      and V beta 9+ T cells derived from developing thymocytes of donor BM origin. The
      Mls-1a reactive T cells are not eliminated in GVHR chimeras in which recipient T
      cells are absent. However, V beta 5+ T cells reactive to I-E plus Etc-1 Ag are
      deleted in the chimeras undergoing GVHR. These results indicate that recipient
      cells which produce tissue-specific antigens (tolerogens) should be taken into
      consideration when generation of the T cell repertoire of donor origin following
      allogeneic BM transplantation is investigated.

PMID- 9269029
TI  - A strategy for generating consistent long-term donor-specific tolerance to solid
      organ allografts.
AB  - Current triple drug immunosuppression while effective, increases the risk of
      opportunistic infection and lymphoproliferative disorders. An alternative
      strategy would be the generation of donor-specific tolerance with short-term
      treatment. The use of donor-specific transfusions (DST) with a single brief
      course of cyclosporine (CsA) and rapamycin (Rapa) has produced promising results
      in animal models, but falls short of uniform tolerance. It was hypothesized that
      a DST/CsA/Rapa protocol administered in the perioperative period and redosed at
      one month might improve on this success in the ACI to Lewis rat heterotopic
      cardiac transplant model. Recipients received no treatment (group 1), a 1 ml DST
      intravenously (i.v.) with CsA 10 mg/kg subcutaneously (s.c.) at D-1 and CsA 2.5
      mg/kg DO6D+13 (group 2), DST/CsA as dosed above with intraperitoneally (i.p.)
      Rapa 1 mg/kg D+36D+7 (group 3), DST/CsA/Rapa as above with all components redosed
      at one month (group 4), DST/CsA/Rapa with only CsA and Rapa repeated (group 5),
      and DST/CsA/Rapa with CsA redosed and Rapa continued indefinitely (group 6).
      Comparison of permanent survival (longer than 200 days) between protocols
      revealed groups 4-6 were significantly greater than control groups 1-3. Donor
      specificity was verified in group 6, where three permanent survivors received a
      second cardiac allograft from a Buffalo rat donor and rejected these grafts
      almost as quickly as untreated strain pair matched controls 21 +/- 1 days vs 30.3
      +/- 5 days. Animals from group 6 displayed a greatly reduced mixed lymphocyte
      response to ACI cells but not to third-party cells. The percentage of T cells
      producing cytokines was reduced and shifted toward Th-2 type cytokines (IL-4).
      Thus, a repeated cycle of this brief DST/CsA/Rapa treatment appears to generate
      consistent permanent graft survival (up to 91%) that exceeds previously studied
      tolerance inducation protocols and is donor specific.

PMID- 9269030
TI  - Clinical significance of selective decline of donor-reactive IL-2-producing T
      lymphocytes after renal transplantation.
AB  - Limiting dilution analysis technique was used to enumerate the circulating
      precursor frequency of donor and third-party-reactive helper T lymphocytes
      (HTLpf) in 28 renal allograft recipients before (pre-tx) and at three intervals
      (T1: 60-90 days, T2: 120-180 days, T3: 360-1620 days) after transplantation (post
      tx). Two patterns of responses were identified, in group 1 (n = 12), a five to 31
      fold reduction of donor-reactive HTLpf (ranging from 1/19231-1/62500) occurred
      within 90-1620 days post-tx, while in group 2(n = 16), no significant changes of
      donor-reactive HTLpf were seen. In both groups, the third-party-reactive HTLpf in
      most of these patients remained largely unchanged throughout the study period.
      The number of HLA-DR mismatches, total number of rejection episodes, serum
      creatinine levels, and biopsy findings at T3 were compared in both groups using
      Fisher's exact probability, and the Mann-Whitney test. We found that 11 patients
      (92%) in group 1 were HLA-DR compatible with donors, while nine (56%) patients in
      group 2 were HLA-DR compatible with donors, p = 0.04. In group 1 eight rejection
      episodes occurred in five (41.6%) patients during the study period, compared to
      33 in 13 (81%) patients in group 2, p = 0.03. Group 1 had a significantly lower
      serum creatinine level (at T3); median: 136 vs 165 mumol/l for group 2, p = 0.03.
      Biopsy indicated no rejection (at T3) in eight (66%) patients in group 1 as
      compared to three (18%) patients in group 2, p = 0.03. Taken together, these
      results indicate that the frequency of circulating HTLpf correlate with the
      clinical status of the graft. Therefore monitoring of HTLpf in the peripheral
      blood could be useful in predicting graft outcome and selecting patients for
      reducing immunosuppression.

PMID- 9269031
TI  - Kinetics of IL-2 and IL-4 mRNA and protein production by graft-infiltrating
      lymphocytes responsible for rejection after clinical heart transplantation.
AB  - During cardiac rejection we studied the kinetics of IL-2 and IL-4 mRNA and
      subsequent protein production by in vivo primed graft-infiltrating lymphocytes
      (GIL), using semiquantitative RT-PCR and ELISA. Following in vitro stimulation
      with either donor or third-party antigens, mRNA expression of IL-2 and IL-4 were
      already detectable 1-2 h after stimulation, while their protein production could
      be measured from 4 h onwards at least until 48 h. At both the mRNA and protein
      level, we measured a donor-specific signal for IL-2 and for IL-4 production (p =
      0.02), while the relative donor-specific IL-2 mRNA level was significantly higher
      than the relative IL-4 mRNA level (p = 0.002). These observations suggest that
      after in vitro challenge with donor antigens, GIL obtained from rejecting cardiac
      allografts predominantly produce IL-2 mRNA and protein.

PMID- 9269032
TI  - Cytomegalovirus infection induces anti-endothelial cell antibodies in cardiac and
      renal allograft recipients.
AB  - Cytomegalovirus (CMV) infection represents a significant morbidity factor for
      transplant recipients. CMV infection has an association with the development of
      allograft rejection (AR) through graft endothelial cell (EC) damage, but the
      mechanisms are not yet clear. There are few reports addressing the role of
      humoral immunity in vascular EC injury mediated by CMV infection whereas many
      reports are available regarding the mechanism(s) of CMV-associated allograft EC
      injury mediated by cellular immunity. Here we examine the incidence of CMV
      infection in 40 cardiac and 25 renal allograft recipients using polymerase chain
      reaction (PCR) techniques. We also monitored sera for the development of anti-EC
      antibodies (AECA) using an ELISA with human umbilical vein ECs as targets, and IL
      2 levels using an ELISA. AECA levels (immunoglobulin-G and immunoglobulin-M) were
      significantly elevated in allograft recipients who demonstrated CMV-PCR
      positivity when compared with the CMV-PCR negative group (IgG: 23.1 +/- 16.4 vs
      4.7 +/- 4.5, p < 0.0001; IgM: 47.0 +/- 53.6 vs 7.0 +/- 11.2, p < 0.0001). Serum
      AECA (IgG and IgM) levels increased one to four weeks after CMV DNA was detected
      and elevated AECA levels persisted for at least one to two months, and sometimes
      for several months. Elevated AECA levels correlated well with serum IL-2 levels.
      These results suggest that CMV infection is associated with an increased humoral
      immune response to EC antigens, which may be a risk factor for vascular
      rejection, chronic rejection and decreased allograft survival.

PMID- 9269033
TI  - Monoclonal antibody to the HLA class I alpha 3 domain inhibits T cell activation
      and prolongs cardiac allograft survival in HLA-transgenic mice.
AB  - Antibodies recognizing MHC class I molecules expressed on the surface of T cells
      have been shown to inhibit T cell responses in vitro. These findings suggested
      that therapy with such an antibody may prevent rejection and promote graft
      acceptance. We therefore tested the effect of an anti-HLA class I alpha 3 domain
      antibody (TP25.99) in vivo using transgenic C57BL/6 mice expressing HLA-B2705.
      Flow cytometric analysis confirmed the binding of TP25.99 to normal human
      peripheral blood lymphocytes and to mouse spleen cells, bone marrow cells and
      thymocytes isolated from hemizygous (+/-) transgenic littermates but not from
      homozygous (-/-) littermates. TP25.99 inhibited OKT-3-induced, but not
      PMA+ionomycin-induced, proliferation of human peripheral blood lymphocyte as well
      as anti-CD3 or Con A-induced proliferation of HLA+ mouse T cells. Both intact
      monoclonal antibody TP25.99 and TP25.99 Fab inhibited T cell proliferation.
      Reduced proliferation was associated with suppressed production of interleukin-2
      as measured by ELISA. The efficacy of TP25.99 Fab in vivo was evaluated in a
      heart allograft model. Antibody therapy of (H-2h, B2705+) transgenic recipients
      of allogeneic Balb/c (H-2d) heart grafts prolonged graft survival significantly
      (MST = 19.8 +/- 6.4, p = 0.003) compared to treated (H-2b, B2705-) (MST = 9.17 +/
      2.2) or untreated (H-2b, B2705+) (MST = 10.0 +/- 2.8) transgenic recipients.
      This demonstrates that immunomodulation through anti-HLA class I antibody therapy
      can lead to prolongation of graft survival.

PMID- 9269034
TI  - Long-term alloreactive T cell lines and clones express a limited T cell receptor
      repertoire.
AB  - Alloreactive T cells recognize either determinants of the intact donor MHC
      molecules displayed on the surface of transplanted-cells or peptide fragments of
      donor antigens associated with self-MHC molecules by means of their T cell
      receptors (TCR). To investigate the relationship between the TCR beta chain
      structure and allorecognition, we established and characterized four long-term T
      cell lines and seven T cell clones derived following a mixed lymphocyte reaction
      (MLR) between fully histoincompatible DA (RT1a) and LEW (RT1(1)) rat lymph node
      cells. These DA anti-LEW T cells were phenotypically CD4+, CD8-, alpha beta TCR+
      and produced interferon-gamma but not IL-4, consistent with being Th1 CD4+ T
      cells. As might be expected, these cells were not significantly cytotoxic and did
      not display suppressor activity. Analysis of the TCR beta chain gene structure
      revealed a very restricted repertoire in both long-term lines and clones. The
      TCRBV6S1 gene was present in 15/21 of the alloreactive T cell mRNA transcripts
      but only 1/12 of unstimulated DA splenic TCR mRNA transcripts (p = 0.0018).
      Similarly, the TCRBJ2S1 gene was also used frequently in the alloreactive
      transcripts (17/21) but in only 2/12 unstimulated splenic transcripts (p =
      0.0013). Furthermore, all 15 of the alloreactive TCRBV6S1 transcripts had a
      distinctive four amino acid N region motif not present in any of the unstimulated
      TCR transcripts (p = 0.0003). These experiments reveal a distinct homogeneity
      amongst stable allogeneic T cells in culture. If these results reflect the
      situation in vivo, the possibility exists that specific immunotherapy may be
      successful in preventing allograft rejection.

PMID- 9269035
TI  - T cell receptor usage by HLA-DR3-specific T cell clones isolated from a renal
      allograft.
AB  - In order to evaluate the T cell receptor (TCR) usage by clones of human allograft
      infiltrating lymphocytes, this study utilized polymerase chain reaction (PCR)
      amplification of TCR transcripts from five clones which were previously shown to
      react with a human leucocyte antigen (HLA)-DR3 mismatch between a living related
      kidney donor and recipient. The five CD4+ (CD8-) clones, which were selected for
      TCR analysis, proliferated in response to HLA-DR3 and three of the clones were
      also cytotoxic against the same target cells. After identification of the TCRAV
      and TCRBV usage of the clones, the sequence of the TCR alpha and beta were
      determined by direct sequencing of the PCR product. The results indicate that
      several different TCRAV and TCRBV gene segments are used among the different
      clones, but the two clones that were both cytotoxic and proliferative in response
      to HLA-DR3 shared identical TCRAV27-J42-C and TCRBV13-D1-J1S2-C1 transcripts. The
      additional three clones showed various TCRAV and TCRBV transcripts, but
      evaluation of the CDR3 region of the TCR beta chain, corresponding to the peptide
      antigen binding sites, demonstrated shared amino acid motifs which resulted both
      from germline sequences and combinations of n-region and germline-derived codons.
      These results suggest that the repertoire for anti-HLA-DR3-reactive clones can
      include a diverse expression of TCR, but there may be selection for some clones,
      as well as conserved motifs in the CDR3 region of anti-DR3 specific clones.

PMID- 9269037
TI  - The immunological role of biliary epithelial cells in human liver transplant
      rejection.
AB  - From histopathological analyses after liver transplantation it is evident that
      the biliary epithilium is an important target for leucocytes of the graft
      recipient. Besides clinical and histopathological investigations undertaken by
      several authors it was also endeavoured to determine the immunological impact of
      the biliary epithelial cells (BEC) in vitro. As for the intrahepatic BEC, in
      vitro studies proved to be restricted owing to difficult isolation procedures and
      the limited number of cells yielded from transplanted organs. Therefore, studies
      on cultured extrahepatic BEC served as a model for the immunological features of
      the biliary epithelium in transplantation. Herein, in vivo and in vitro studies
      dealing with BEC and immunologically mediated hepatic disorders are reviewed in
      order to understand better the pathogenesis after liver transplantation.
      Furthermore, possible underlying mechanisms of BEC-directed immunity with regard
      to BEC-leucocyte interactions are discussed.

PMID- 9269036
TI  - Donor pretreatment with leflunomide has an adverse effect on rat cardiac
      allograft survival.
AB  - The effect of leflunomide (Lef) donor pretreatment (DPT) on rat cardiac allograft
      survival was investigated. In untreated Lewis recipients of untreated DA hearts,
      median graft survival was 5 days. DPT (Lef 5 or 10 mg/kg per day for 30 days)
      reduced median graft survival to 4.0 and 4.5 days, respectively. In
      immunosuppressed (Lef 5 mg/kg for 10 or 30 days) Lewis recipients of untreated DA
      hearts, median graft survival was 21 and 33 days, respectively. DPT with Lef 5
      mg/kg per day for 5 days or 30 days reduced median graft survival to 12 and 23.5
      days, respectively (p < 0.05). DPT with Lef resulted in earlier graft rejection
      but the histological appearance at the time of rejection was the same as in
      untreated controls. DPT with Lef resulted in a 40% reduction in MHC class II
      positive cells in the heart. Histological examination of rejecting hearts showed
      no obvious difference in the nature of the rejection process between DPT and
      untreated control hearts. The paradox between class II reduction but earlier
      rejection indicates that DPT is exerting a deleterious effect through some
      unrecognized property of the graft.

PMID- 9269038
TI  - Dipeptidyl peptidase IV (CD26) activity in human alloreactive T cell subsets
      varies with the stage of differentiation and activation status.
AB  - Dipeptidyl peptidase IV (DPP IV), also known as CD26, is a transmembrane serine
      aminopeptidase which has an ontogenically related expression on T cells and
      participates on several immunological functions. CD26 appears to play an
      important role in alloimmunity during host T cell activation subsequent to
      alloantigen encounter and is a way by which effector T cells traverse graft
      endothelial barriers. In order to help to elucidate the role of the CD26 molecule
      in alloimmune responses, DPP IV activity and CD26 antigenic expression were
      assessed during the initial phases of completely MHC-disparate human mixed
      lymphocyte reactions (MLRs) and in several long-term alloreactive T cell clones.
      Our methods involved the use of a rhodamine-110-conjugated dipeptide substrate
      specific for DPP IV in two-colour cytofluorographic analysis that allowed
      stimultaneous lineage marker evaluation. Polyclonal populations of alloreactive
      CD4 and CD8 T cells contained DPP IV activity at 1 and 10 min of incubation that
      was variably elevated from resting T cells with the enzyme activity confined to
      CD26+ cells. T cell clones derived from MLRs were established with IL-2
      supplementation and alloantigen restimulation and had reduced CD62L expression
      with functional specificity to the stimulating MHC. While CD26 expression
      remained stable, DPP IV activity was variable in the alloreactive T cell clones,
      with enzyme function in the latter appearing to coincide with the timing of
      alloantigen restimulation. These studies demonstrate that DPP IV activity varies
      among phenotypically distinct alloreactive T cell subsets and appears to be
      altered with the activation status of the effector cells. These findings raise
      the potential of a role for CD26/DPP IV in the generation of specific
      alloimmunity. With this methodology, it may be possible to reveal whether
      specific alterations in the activity of this molecule in T cell populations
      promote graft acceptance and to determine the molecular requirements for these
      changes.

PMID- 9269039
TI  - Lack of in vitro synergy of clinically used antibodies specific for ICAM-1 and
      LFA-1.
AB  - Antibodies blocking adhesion molecules such as leucocyte function antigen (LFA)-1
      (CD11a) and intercellular adhesion molecule (ICAM)-1 (CD54) are currently under
      clinical investigation for rejection prophylaxis in organ transplantation. In a
      murine model a combined though not a single application of antibodies against LFA
      1 and ICAM-1 can induce tolerance towards heart transplants. No information
      regarding a possible synergistic action in man is as yet available. To fill this
      blank we tested the immunosuppressive capacity of ANTILFA (alpha-LFA-1)- and
      BIRR1 (alpha-ICAM-1) on human cells in vitro alone and in combination. Allogeneic
      venous endothelial cells, the lymphoblastoid cell line MSAB or peripheral blood
      mononuclear cells were used as stimulation. DNA synthesis, IL-2 production and
      cytotoxic T cell lysis were measured to assess T cell response. The strongest
      antibody effects were seen when endothelial cells were used as stimulators with
      the T cell response being assessed by IL-2 production. Most assays showed a
      similar immunosuppressive effect of LFA-1 and ICAM-1 blocking while the
      combination of both antibodies was not significantly more effective than each
      antibody alone. Thus our data do not provide a rationale for clinical trials
      using a combination of these antibodies.

PMID- 9269040
TI  - Experimental studies on lung mechanics, gas exchange and oxygen delivery under
      open lung conditions. Mechanical ventilation with decelerating versus constant
      inspiratory flow.

PMID- 9269041
TI  - Nitric oxide, nitrogen metabolism and inflammatory respiratory disease. An
      hypothesis.

PMID- 9269042
TI  - Insulin receptors in human ocular tissues. Immunohistochemical demonstration in
      normal and diabetic eyes.
AB  - The alpha- and beta-subunits of the insulin receptor have been localised in human
      eyes by immunohistochemistry. In the normal eye staining for both receptor
      subunits was distinct at the same sites of the anterior part of the eye, i.e.
      cornea, smooth muscle and epithelium of the ciliary body and the lens capsule. In
      the retina, the receptor was clearly demonstrated in the nerve fibre layer, the
      ganglion cells and Muller cells, the outer nuclear layer, inner segments of rods
      and cones, the outer limiting membrane and in the pigment epithelium. In eyes
      with diabetic retinopathy, the receptor did not stain in the inner segments of
      the rods and cones and the staining of the other layers was weak. Endothelial
      cells stained positively in normal and diabetic eyes, but pericytes of normal and
      new vessels did not stain. The receptor staining did not change in cornea, iris,
      ciliary body and lens. All together, the study shows that alpha- and beta
      subunits of the insulin receptor are present in the retina, and that the staining
      reaction for the receptor is reduced in diabetes. To what extent these findings
      are of importance for the development of diabetic retinopathy, remains to be
      clarified.

PMID- 9269043
TI  - The antibody-neutralisation of PDGF, CSF-1, TGFb2,3, EGF and EGF-receptor in
      utero in pre-implantation mice.
AB  - The aim of this study was to determine whether specific growth factors, those
      shown to be involved using PCR and immunohistochemistry, are necessary for the in
      vivo mechanisms of normal implantation in mice. The abdomen of pregnant female
      mice were opened surgically on day 4 to expose the uterine horns, which were
      microinjected with specific neutralising antibodies against PDGF, CSF-1, TGFb2,3,
      EGF and EGF-receptor. At autopsy on day 12, the numbers, positions and sizes of
      all implantation and resorption sites were recorded. Sham-operation controls were
      utilised to evaluate the implantation model. Normal female mice exhibited a mean
      of 6.24 implantation sites per uterine horn. Sham-operated mice exhibited a 30.8%
      reduction in implantation compared with normals, and saline-injected mice
      exhibited a 45.7% reduction. Antibody-injected horns were compared with horns
      injected with saline and horns injected with heat deactivated antibody. All
      neutralising antibodies tested resulted in significant reductions in the
      implantation rate and the size of the implantation site. These experiments
      confirm, in vivo, participation of the specific growth factors tested in the
      mechanisms of murine implantation, as alluded to previously by evidence from PCR
      in vitro stimulatory and immunohistochemical work.

PMID- 9269044
TI  - Assessment of cognitive function. A study with the Swedish version of the Kaufman
      Assessment Battery for Children.
AB  - The Kaufman Assessment Battery for Children (K-ABC) is a test that measures
      cognitive function in children. A Swedish version has been produced for use as a
      research instrument in a longitudinal follow-up study of children that needed
      neonatal intensive care at the Uppsala University Children's Hospital, Sweden. A
      study using this Swedish version was carried out in 26 healthy children 10 years
      of age attending a primary school in Uppsala, Sweden. The results showed that the
      Swedish version of the K-ABC well discriminates cognitive function in children
      aged 10 years. The scores of all subtests were distributed over the scale and the
      mean scores mostly corresponded to near average or above average performance when
      compared with the mean values obtained in the standardization sample.

PMID- 9269045
TI  - Elimination of abnormal toxicity test for sera and certain vaccines in the
      European Pharmacopoeia.

PMID- 9269046
TI  - DNA vaccination followed by macromolecular multicomponent peptide vaccination
      against HIV-1 induces strong antigen-specific immunity.
AB  - The induction of a strong and long-lasting immunity characterized by both a
      humoral and cell-mediated immune (CMI) response is one of the most important
      considerations in developing an effective HIV vaccine. In previous studies, we
      have independently developed both DNA vaccine and macromolecular multicomponent
      peptide vaccine (VC1) candidates. In the present study, we attempted to optimize
      the vaccination protocol using mice, guinea pigs, rabbits and Macaca fuscata
      monkeys. Repeated vaccination with VC1 induced a substantial level of multivalent
      antibodies which neutralized various HIV-1 strains, as determined using a p24
      inhibition assay. On the other hand, repeated immunization with DNA vaccine
      induced and sustained high levels of cytotoxic T lymphocytes (CTLs). In addition,
      when DNA vaccination was followed by multicomponent peptide vaccination, levels
      of both humoral immunity and CMI increased, and this effect continued for at
      least 10 months. These data clearly demonstrate that for inducing HIV-1 specific
      immunity, immunization with DNA vaccine followed by VC1 boosting produces better
      results than immunizing with either vaccine alone.

PMID- 9269047
TI  - Study of immunogenicity and virulence of bovine herpesvirus 1 mutants deficient
      in the UL49 homolog, UL49.5 homolog and dUTPase genes in cattle.
AB  - We previously reported that the bovine herpesvirus 1 (BHV 1) gene homologous to
      herpes simplex virus gene UL49 is dispensable; nevertheless, a mutant with the
      UL49 homolog (UL49 h) gene deletion exhibited significantly impaired growth in
      cell culture. To further evaluate the role of the UL49 h in virus infectivity in
      the natural host of BHV 1, the pathogenesis of the UL49 h negative mutant was
      studied in cattle. An additional mutant with a combined defect in UL49 h, UL49.5
      h and dUTPase genes was also studied in parallel. We found that both mutants were
      avirulent in cattle inasmuch as intranasal (i.n.) administration of either
      mutants induced no apparent clinical disease, nor did animals receiving the
      mutants shed virus. Following i.n. inoculation with the mutants animals developed
      low levels of serum neutralizing (SN) antibodies, and were partially protected
      against wild-type BHV 1 challenge. Intramuscular immunizations with either mutant
      induced good SN titers, and moreover, they induced nearly complete protection
      against respiratory challenge with wild-type virus. The results from this study
      establish that BHV 1 UL49 h is an important virulence factor, and also suggest
      that deletion of the nonessential viral genes UL49 h, UL49.5 h and dUTPase may be
      useful in developing recombinant BHV 1 vaccines or BHV 1-based vaccine vectors.

PMID- 9269048
TI  - Enhancement of the immune response to non-replicating herpes simplex virus type-1
      preparations by mucosal administration in the presence of cholera toxin.
AB  - Different immunization regimes were compared in order to enhance the immune
      response following mucosal administration of non-replicating HSV-1 preparations
      to mice. The serum anti-HSV Ig response following intragastric administration of
      heat or UV inactivated HSV-1 strain SC16 was compared with that elicited by an
      attenuated derivative of SC16 (TKDM21). The highest response followed
      immunization with TKDM21 and this was markedly enhanced by repeated intragastric
      administration, reaching ca 35% of that elicited following a cutaneous infection
      with live virus. Repeated doses of killed virus produced only a minimal increase
      in the response even when given intranasally (i.n.). However, cholera toxin and
      its B-subunit with UV-inactivated virus or a mixture of purified viral
      glycoproteins enhanced the anti-HSV response after i.n. immunization and produced
      antibody levels equivalent to those following intragastric delivery of live
      TKDM21.

PMID- 9269049
TI  - Oral immunization of rainbow trout with antigen microencapsulated in poly(DL
      lactide-co-glycolide) microparticles.
AB  - The model protein antigen, human gamma globulin (HGG) was microencapsulated in
      poly(DL-lactide-co-glycolide) microparticles and administered orally to rainbow
      trout. Oncorhynchus mykiss (Walbaum, 1792). Using a Western blotting technique it
      was demonstrated that the dynamics of passage through the gut were different for
      the microencapsulated and soluble antigen. The association of HGG with
      microparticles increased the retention time of the antigen in the stomach and
      delayed its entry into the intestinal region. After the delivery of
      microencapsulated HGG, antigen was detected in gut contents in fragmented form
      which suggested that some of the antigen was present at the particle surface and
      therefore susceptible to proteolysis. However, a greater amount of intact antigen
      was detected in the posterior intestine and in the bloodstream of fish, which
      were administered with microparticle-associated than soluble antigen, indicating
      that the antigen was partially protected. Immunization with microencapsulated HGG
      resulted in the detection of specific antibody in the serum but levels were not
      significantly greater than after the delivery of soluble antigen. However,
      specific antibody was detected in the intestinal mucus of fish which were
      administered with the microencapsulated antigen after boosting with soluble HGG
      but not in fish which were primed with the soluble antigen.

PMID- 9269050
TI  - A sub-unit vaccine elicits IgG in serum, spleen cell cultures and bronchial
      washings and protects immunized animals against pneumonic plague.
AB  - In this study, the protection afforded against aerosolized Yersinia pestis by
      injection of an alhydrogel-adsorbed sub-unit vaccine has been compared with that
      given by an existing killed whole cell vaccine licensed for human use. The sub
      unit vaccine protected mice against exposure to > 10(4) colony-forming units
      (c.f.u.) of virulent plague organisms (100 LD50 doses), whereas the whole cell
      vaccine provided only 50% protection against 1.8 x 10(3) c.f.u. In sub-unit
      vaccinees, IgG to each of the F1 and V antigens contained in the vaccine, was
      detected in serum, on direct secretion by spleen cells and in broncho-alveolar
      washings (BAL). In killed whole cell vaccinees, physiologically significant
      levels of IgG to F1 only were detectable in equivalent samples. Levels of F1
      specific IgG in serum, secreted from spleen cells and in BAL were significantly
      higher (P < 0.01) in sub-unit compared with killed whole cell vaccinees. IgA was
      not detected in BAL from intra-muscularly dosed sub-unit vaccinees and thus the
      protection achieved against inhalational challenge with Yersinia pestis is
      attributed to the induction of systemic immunity to both the F1 and V antigens in
      the sub-unit vaccine. The enhanced protective efficacy of this sub-unit vaccine
      over an existing vaccine has been demonstrated in an animal model of pneumonic
      plague.

PMID- 9269051
TI  - DNA vaccination using expression vectors carrying FIV structural genes induces
      immune response against feline immunodeficiency virus.
AB  - Following inactivated virus vaccination trials, the surface glycoprotein gp120 of
      the feline immunodeficiency virus (FIV) was considered as one of the determinants
      for protection. However, several vaccination trials using recombinant Env protein
      or some peptides failed to induce protection. To understand the role of the gp120
      protein in vivo, we vaccinated cats with naked DNA coding for FIV structural
      proteins gp120 and p10. We analyzed the ability of these vaccinations to induce
      immune protection and to influence the onset of infection. Injection in cat
      muscles of expression vectors coding for the FIV gp120 protein induced a humoral
      response. Cats immunized twice with the gp120 gene showed different patterns
      after challenge. Two cats were, like the control cats, infected from the second
      week after infection onwards. The two others maintained a low proviral load with
      no modification of their antibody pattern. The immune response induced by gp120
      DNA injection could control the level of viral replication. This protective-like
      immune response was not correlated to the humoral response. All the cats
      immunized with the gp120 gene followed by the p10 gene were infected, like the
      control cats, from the second week but they developed a complete humoral response
      against viral proteins after challenge. Furthermore, they showed a sudden but
      transient drop of the proviral load at 4 weeks after infection. Under these
      conditions, one injection of the p10 gene after one injection of the gp120 gene
      was not sufficient to stimulate protection. On the contrary, after a period, it
      seems to facilitate virus replication.

PMID- 9269052
TI  - Selective unresponsiveness to HBsAg vaccine in newborns related with an in utero
      passage of hepatitis B virus DNA.
AB  - Thirty four out of 158 (22%) newborns to mothers chronically infected by the
      hepatitis B virus (HBV) did not produce antibodies (Ab) to HBsAg 1 month after
      the last injection of the HBV vaccine supplemented with HBV specific
      immunoglobulins. At birth, HBV genome was detected by polymerase chain reaction
      (PCR) in the peripheral blood mononuclear cells (PBMC) of a large majority (28
      out of 34) of these non-responder newborns but never in the other newborns who
      responded to the HBsAg vaccine. HBV genome was detected in serum, only in some
      cases (nine out of 34) and never in the absence of HBV DNA in PBMC. For nine out
      of 14 followed newborns, the absence of response was transitory since anti-HBs
      Abs appeared after 15 months, without booster, while the HBV genome had
      disappeared. Unresponsiveness was specific to the HBV envelope protein since all
      late responders and 15-months-non-responders to the HBsAg vaccine produced normal
      levels of Abs to the three poliovirus serotypes, to tetanus toxoid and to the
      pneumococcus polysaccharides. An in utero induced immune tolerance to low doses
      of HBsAg appears as the most plausible hypothesis to explain this
      unresponsiveness to HBV vaccine.

PMID- 9269053
TI  - Placebo-controlled evaluation of a modified life virus vaccine against feline
      infectious peritonitis: safety and efficacy under field conditions.
AB  - A modified live virus vaccine against feline infectious peritonitis (FIP) was
      evaluated in a double blind, placebo-controlled field trial in two high-risk
      populations. The vaccine was found to be safe and efficacious in one population
      of cats that had low antibody titre against feline coronavirus (FCoV) at the time
      of vaccination. Although clinically healthy at the time of vaccination,
      retrospectively some vaccinees that later came down with FIP were found to be RT
      PCR positive for FCoV in plasma and showed changes in blood parameters consistent
      with early stage of FIP. It is concluded that vaccination can protect cats with
      no or low FCoV antibody titres and that in some cats vaccine failure was probably
      due to pre-existing infection.

PMID- 9269054
TI  - A comparison of natural and recombinant cholera toxin B subunit as stimulatory
      factors in intranasal immunization.
AB  - Cholera toxin B (CTB) is often envisaged and used as an immune stimulating agent
      in protocols for mucosal immunization. However, the nature of the CTB used
      (natural vs recombinant) is frequently not taken in consideration. This is
      important since the usage of natural CTB in mucosal immunization regimen and the
      mucosal response resulting from such an immunization can be effected by the
      presence of the CTA subunit in commercial CTB preparations. To clarify this, we
      have compared natural vs recombinant CTB in an intranasal (i.n.) mucosal
      immunization procedure using ovalbumin (OVA) as antigen. The results show that
      recombinant CTB induces similar immune responses like natural CTB. Furthermore,
      our experiments show that covalent coupling of OVA to CTB is not required for the
      induction of OVA specific mucosal and systemic immune responses upon i.n.
      immunization.

PMID- 9269055
TI  - Efficacy of repeated annual immunization with inactivated influenza virus
      vaccines over a five year period.
AB  - Some reports have suggested that influenza virus vaccine is less effective in
      persons that have received prior annual vaccination(s) than in those receiving it
      for the first time. This issue was addressed by evaluating the efficacy of annual
      influenza vaccinations over a 5 year period in healthy adults employing
      commercially-available, inactivated whole-virus vaccine. Influenza vaccination
      had minimal effects on overall respiratory illnesses during epidemic periods.
      However, it reduced influenza virus shedding by an average of 38.8% and conferred
      protection against influenza virus infection during each epidemic. Some variation
      in infection rates were noted between vaccine groups given one or more than one
      annual immunization, and between years, but no consistent pattern of differences
      was noted in relation to number of successive years of vaccination. These results
      suggest that the current recommendation for annual influenza vaccination of
      persons at special risk of serious disease and complications is appropriate, but
      that continued efforts to improve the effectiveness of our prophylactic measures
      against influenza are needed.

PMID- 9269056
TI  - Influence of host related factors on the antibody response to trivalent oral
      polio vaccine in Tunisian infants.
AB  - The low efficiency of trivalent oral polio vaccine (TOPV) in inducing protective
      antibody titres to polio3 is a problem of great importance in many regions of the
      world. A prospective study was conducted in 121 Tunisian infants aged 3 months
      during routine immunization with TOPV under carefully controlled conditions.
      Seroconversion rates to polio1, polio2 and polio3, one month after the third
      dose, were 94.7, 100 and 89.5%, respectively. The kinetics of the antibody
      response showed delayed and more difficult responses to polio3 compared to polio2
      and polio1. The following host related factors, previously suggested to interfere
      with the immune response, were assessed: maternal antibodies; breast-feeding;
      concurrent enteric infections; and other illnesses. The main factor associated
      with the lack of seroconversion was concurrent infection with non-polio
      enteroviruses (NPE) which was found in 50% of non-responders to polio1 and/or to
      polio3 during the vaccination protocol whereas no NPE was isolated in vaccine
      responders. The other studied factors seemed not to interfere in the infants
      according to the locally adopted vaccination schedule and to the specific socio
      economic conditions.

PMID- 9269057
TI  - Safety and immunogenicity of a respiratory syncytial virus subunit vaccine (PFP
      2) in the institutionalized elderly.
AB  - The safety and immunogenicity of purified fusion protein (PFP-2) respiratory
      syncytial virus (RSV) vaccine was evaluated in an open label study in 37 frail
      institutionalized persons over age 65. Vaccination was well tolerated without
      significant side-effects. Thirty-six of 37 volunteers completed the study.
      Nineteen of 36 (53%) vaccinees had a greater than or equal to fourfold increase
      in IgG to F protein at 4 weeks and 17 (47%) had a greater than or equal to
      fourfold rise in neutralizing titers to either group A or B virus. Although
      response rate to PFP-2 vaccine in the frail elderly was somewhat diminished
      compared to results in the healthy elderly, the vaccine was well tolerated and
      relatively immunogenic.

PMID- 9269058
TI  - Associations of prevaccination antibody levels with adverse reactions to
      pneumococcal and influenza vaccines administered simultaneously in the elderly.
AB  - The association of prevaccination antibodies with the adverse reactions seen
      after vaccination was studied in 85 elderly subjects (65-90 years) vaccinated
      simultaneously with pneumococcal and influenza vaccines. The subjects with a
      temperature rise (9% of vaccinees) had significantly higher prevaccination
      antibody levels to pneumococcal capsular polysaccharides (PPSs) than those
      without a temperature rise; no difference was seen in their haemagglutination
      inhibiting (HI) influenza virus antibody levels. Pain in the left arm (the
      pneumococcal vaccine injection site) occurred in 45% of the subjects and was
      likewise associated with elevated PPS antibody levels. Pain at the site of
      influenza vaccine injection (the right arm) seen in 33% of the vaccinees was
      significantly more common among those who had previously received influenza
      vaccine, but was not associated with elevated HI antibody levels. In conclusion,
      prevaccination pneumococcal but not influenza antibodies were associated with
      both systemic and local reactions following vaccination.

PMID- 9269059
TI  - Further studies on the efficacy of a live vaccine against mastitis caused by
      Streptococcus uberis.
AB  - Three groups of dairy cows were immunized by subcutaneous (s.c.) administration
      of a preparation of live Streptococcus uberis (strain 0140J) and an intramammary
      infusion of a soluble surface extract derived from same the bacteria. Animals in
      Groups 1 and 2 received two s.c. vaccinations plus an intramammary inoculation.
      Animals in Group 3 received two s.c. vaccinations but did not receive the
      intramammary infusion. In addition to the vaccinated animals, each group also
      contained two non-vaccinated (control) animals. All animals were challenged
      experimentally by intramammary infusion (in two quarters per animal) of ca 100
      c.f.u. of S. uberis (strain 0140J or C221) and monitored for clinical signs of
      disease, bacterial numbers in milk, somatic cell count in milk, and daily milk
      yield for the following 10 days. Animals in Group I were challenged with strain
      0140J. Only one out of six challenged quarters of three vaccinated cows developed
      clinical disease compared to all (four out of four) quarters of non-vaccinated
      cows. Animals in Group 2 were challenged with strain C221. All challenged
      quarters of three vaccinated (six out of six) and two non-vaccinated (four out of
      four) cows developed clinical mastitis. Animals in Group 3 were challenged with
      strain 0140J. Five out of eight quarters on four vaccinated cows developed
      clinical mastitis but the onset was delayed in comparison with that in both non
      vaccinated cows in which four out of four challenged quarters developed clinical
      mastitis. These results indicated that vaccination with live S. uberis protects
      against challenge with the homologous strain but was less effective against a
      heterologous strain. Reduced protection was also seen when the intramammary
      booster was omitted.

PMID- 9269060
TI  - A randomized, placebo-controlled study of oral cimetidine as an immunopotentiator
      of parenteral immunization with a group B meningococcal vaccine.
AB  - Cimetidine (CIM) is an H2-receptor antagonist with a long history of clinical use
      in peptic ulcer disease. In addition to its inhibitory effect upon gastric acid
      secretion, CIM can also block histamine-mediated immunosuppression by inhibiting
      H2 receptors on suppressor T cells. CIM results in immunoaugmentation of both
      cellular and humoral immunity by this mechanism and has been used clinically in
      the treatment of chronic infectious and neoplastic diseases. We postulated that
      orally administered CIM, like an adjuvant, could augment the immunologic response
      to a parenteral vaccine. To test this hypothesis, a randomized placebo (PLB)
      controlled, double-blinded study in 14 healthy volunteers was performed using a
      Group B meningococcal outer membrane protein (OMP) vaccine administered twice, 6
      weeks apart. Volunteers were randomized within pairs defined by their screening
      OMP antibody titers to receive either CIM or PLB which was administered for 5
      days, beginning 2 days before each of the two immunizations. All 14 volunteers
      completed the study with excellent compliance. Sera were tested for anti-OMP and
      bactericidal antibodies. The groups were comparable in terms of gender
      distribution, age and baseline anti-OMP titers. Reactogenicity to the vaccine was
      mild and comparable between groups. There was little effect of CIM (over PLB) on
      anti-OMP or functional bactericidal antibody levels over time. Geometric means of
      maximum OMP antibody increase over baseline was 3.3-fold (95% CI: 1.8-6.3) for
      CIM and 2.4 for PLB (CI: 1.6-3.7). CIM had a corresponding 3.9-fold increase (CI:
      1.9-8.3) in bactericidal antibody level compared to 2.2 for PLB (CI: 1.4-3.4). We
      conclude that oral CIM was not effective as an immunopotentiator of immunization
      with this group B meningococcal vaccine.

PMID- 9269061
TI  - Immunogenicity and efficacy of baculovirus-expressed and DNA-based equine
      influenza virus hemagglutinin vaccines in mice.
AB  - Two fundamentally different approaches to vaccination of BALB/c mice with the
      hemagglutinin (HA) of A/Equine/Kentucky/1/81 (H3N8) (Eq/KY) were evaluated, that
      is, administration of HA protein vs administration of HA-encoding DNA. Each
      vaccine was tested for its immunogenicity and ability to provide protection from
      homologous virus challenge. HA protein was synthesized in vitro by infection of
      Sf21 insect cells with a recombinant baculovirus. Intranasal administration of
      this vaccine induced virus-specific antibodies, as measured by enzyme-linked
      immunosorbent assay (ELISA), but did not induce virus neutralizing (VN)
      antibodies. This route of administration provided partial protection from virus
      challenge, but interestingly, this protection was completely abrogated, rather
      than enhanced, by co-administration of 10 micrograms of cholera holotoxin. As a
      second approach, mice were directly vaccinated in vivo by Accell gene gun
      delivery of plasmid DNA encoding the Eq/KY HA gene. This approach induced VN
      antibodies as well as virus-specific ELISA antibodies. When two doses of DNA
      vaccine were administered 3 weeks apart, mice were not protected from challenge,
      although they cleared the infection more rapidly than control mice. However, when
      the second DNA vaccination was delayed until 9 weeks after the first, 9 out of 10
      vaccinated mice were completely protected. These results indicate that the time
      between initial and booster DNA vaccinations may be an important variable in
      determining DNA vaccination efficacy.

PMID- 9269062
TI  - The effect of age and weight on the response to formalin inactivated, alum
      adjuvanted hepatitis A vaccine in healthy adults.
AB  - Formalin-inactivated, alum-adsorbed, hepatitis A vaccine was evaluated in 100
      healthy adults who were stratified at enrollment into two age groups: 18-39
      years: n = 50; 40-65 years: n = 50. All individuals received vaccine at 25 U of
      viral antigen. After stratification, both groups were randomized to receive
      either vaccination at 0 and 24 weeks or vaccination at 0.2 and 24 weeks. Subjects
      were bled for serology at 0, 2, 4, 24, 28 weeks and 1 year. The seroconversion
      rate and geometric mean titer (GMT = mIU ml-1) after one dose of vaccine was
      lower for older subjects [second week: < 40 years: 15/25 (60%) (GMT: 12.9). > 40
      years: 5/22 (23%) (GMT: 6.1): fourth week: < 40 years: 20/22 (91%) (GMT: 29.0), >
      40 years: 16/23 (70%) (GMT: 14.3)]. After a second dose at 2 weeks the
      seroresponse improved so that there were no longer differences between age groups
      [24 weeks: < 40: 21/22 (95%) (GMT: 123.9), > 40: 22/23 (96%) (GMT: 106.1)]. A
      third dose at 24 weeks resulted in a 20-40-fold increase in GMT in both age
      groups. As a separate evaluation height, weight, skin fold thickness, and body
      mass index (BMI) were assessed by logistic regression for their ability to
      predict serologic response. Serologic response was significantly associated with
      lower weight (P = 0.032) and BMI (P = 0.024) but not with height or skin fold
      thickness. Hepatitis A vaccine was well tolerated, with no serious adverse
      experiences. Adults older than 40 years appear to respond less well than younger
      adults to a single dose of 25 U of hepatitis A vaccine but equally well after two
      doses of vaccine. The slower antibody response to hepatitis A vaccine in
      overweight individuals was not attributable to skin adipose tissue.

PMID- 9269063
TI  - Molecular basis of Kell blood group phenotypes.
AB  - The molecular basis of different Kell blood group phenotypes is reviewed.
      Sequence analysis of the Kell gene (KEL) established that single base
      substitutions, resulting in amino acid changes, are responsible for the different
      phenotypes. Most of the amino acid substitutions, with the exception of the one
      responsible for expression of KEL6 (Jsa), occur at the amino-terminal half of the
      protein, a domain that has least amino acid homology with a family of zinc
      endopeptidases, which include neutral endopeptidase 24.11 and endothelin
      converting enzyme-1. Some of the genes were expressed in transfected cells and
      typed with alloantibodies to confirm that the identified mutations are
      responsible for antigen expression. Clinical applications of Kell blood group
      genotyping which include prenatal diagnosis to monitor hemolytic disease of the
      newborn are discussed.

PMID- 9269064
TI  - Markers of haemostatic activation before and after blood donation and
      plasmapheresis.
AB  - BACKGROUND AND OBJECTIVES: Previous studies have reported signs of haemostatic
      activation after haemorrhage. The aim of this study was to measure sensitive
      markers for haemostatic activation after blood donation or plasmapheresis in
      healthy donors. MATERIALS AND METHODS: Blood samples were drawn before as well as
      5 min and 1 h after donation in 40 male donors, of whom 29 gave 1 unit of blood
      and 11 underwent plasmapheresis. Standard assays were used. RESULTS: Plasma
      concentrations of the activation markers prothrombin fragment 1 + 2, thrombin
      antithrombin complexes, and von Willebrand factor did not increase after blood or
      plasma donation. CONCLUSIONS: In our opinion, these procedures are safe.

PMID- 9269065
TI  - Heating lyophilised factor VIII does not alter its recognition by specific
      antibodies.
AB  - BACKGROUND AND OBJECTIVES: Alterations of factor VIII (FVIII) during preparation
      procedures can potentially affect its immunogenicity. One method evaluating such
      alterations could be by determining the reactivity of FVIII with specific
      antibodies. MATERIALS AND METHODS: Since heat treatment is currently used to
      reduce the risk of viral transmission, we evaluated the immunoreactivity of
      plasma-derived FVIII before and after heating at different temperatures and for
      different periods. Freeze-dried FVIII was used for these experiments as part of
      the validation procedure of a novel FVIII preparation. RESULTS: Heating FVIII for
      up to 72 h at 80 degrees C does not alter its reactivity with specific rabbit
      antibodies or mouse monoclonal antibodies, although some loss of FVIII activity
      occurred after 72 h. After heating for 2 h at 100 degrees C, a procedure that
      reduced FVIII activity by about 50%, there were still no significant effects on
      FVIII reactivity with monoclonal antibodies. CONCLUSIONS: Freeze-dried
      preparations of plasma-derived FVIII seem to be resistant to heat-induced
      structural denaturation.

PMID- 9269066
TI  - Response of the erythron and erythropoietin to autologous blood donations in
      paediatric subjects. Is erythropoietin supplement necessary?
AB  - OBJECTIVES: This study was undertaken to evaluate the need for erythropoietin
      (Epo) therapy to augment autologous blood collection in adolescents undergoing
      spinal corrective surgery. METHODS: We measured serum Epo and parameters of iron
      metabolism in 35 adolescents undergoing autologous blood collection for
      orthopaedic surgery. Ages of subjects ranged from 11 to 16 years (mean 15.5
      years) with a female predominance. Generally, 10% of intravascular blood volume
      was collected once a week up to a total of three collections. RESULTS: There was
      an average 2.5-fold rise in serum Epo over the period of blood collection. Epo
      increased immediately after blood collection. There was a 1.4-fold rise in
      reticulocyte count, consistent with the Epo response, and an average of 1.5 units
      of red blood cells (200 ml/unit) being produced over this period. Despite this
      there was an average fall of 2 g/dl (15%) in haemoglobin level. Serum ferritin
      and transferrin saturation also fell. CONCLUSIONS: Paediatric subjects are able
      to donate the required units of blood as they have a good Epo response to mild
      anaemia. The amount of blood donated did not exceed their total mobilisable iron
      and the iron supplement was adequate for red cell synthesis.

PMID- 9269067
TI  - Prestorage leukocyte reduction with in-line filtration of whole blood: evaluation
      of red cells and plasma storage.
AB  - OBJECTIVES: Prestorage filtration of blood components appears to be an effective
      method to reduce leukocyte-induced adverse reactions and other complications. To
      determine whether it is better to filter whole blood before component separation,
      we compared the efficiency of in-line filtration of whole blood with that of
      postseparation filtration. METHODS: Blood was collected from normal, healthy
      donors into either regular triple-bag containers or into whole-blood integral
      filter container systems. We then compared the in vitro storage values of
      leukocyte-depleted red blood cell concentrates (RBCC) kept at 4 degrees C, and
      plasma frozen for 1 year with nonfiltered blood components as control. RESULTS:
      All counts of white blood cells after filtration were < 1 x 10(6) per unit. For
      almost all storage parameters no significant differences were found between
      leukocyte-reduced RBCC and control units. The plasma fibrinopeptide A values
      below 30 ng/ml prior to freezing indicate that filtration does not activate the
      coagulation factors. Furthermore, the filtration did not influence either the
      biological values or the coagulation factors of plasma units. CONCLUSIONS: Whole
      blood filtration prior to component preparation seems to offer a useful
      alternative technique for obtaining leukocyte-reduced RBCC and plasma.

PMID- 9269068
TI  - In vitro evaluation of the hemostatic effectiveness of non viable platelet
      preparations: studies with frozen-thawed, sonicated or lyophilized platelets.
AB  - OBJECTIVES: Because of the limited life span of platelets in regular storage
      systems, we were interested in investigating the effects on hemostasis of
      nonliving platelet derivatives. METHODS: We evaluated the effects of different
      platelet preparations on primary hemostasis in a well-established perfusion
      model. Studies were carried out with blood anticoagulated with low molecular
      weight heparin. Similar amounts of frozen-thawed, sonicated or lyophilized
      platelets were added to normal blood or to blood which had been experimentally
      depleted of platelets. Platelet interaction with the subendothelium and fibrin
      deposition were morphometrically evaluated. RESULTS: Addition of nonviable
      platelet preparations to thrombocytopenic blood always promoted a statistically
      significant increase in the deposition of fibrin on the subendothelium, but only
      lyophilized platelets retained some ability to interact with the subendothelium.
      Flow cytometry studies demonstrated the presence of GPIb, GPIIIa and P-selectin
      on lyophilized platelets. CONCLUSIONS: Preparations containing nonviable
      platelets may still retain some hemostatic properties.

PMID- 9269069
TI  - Transfusion-related acute lung injury following random donor platelet
      transfusion: a report of two cases.
AB  - OBJECTIVES: Transfusion-related acute lung injury (TRALI) following random donor
      platelet (RDP) transfusion is a rare complication of transfusion without any well
      documented case reported in the English language literature. We describe 2
      patients in whom TRALI occurred following RDP transfusion. METHODS: Conventional
      clinical and laboratory methods. RESULTS: Both patients developed acute shortness
      of breath 30-60 min after completion of RDP transfusion and required mechanical
      ventilatory support. Chest X-ray (CXR) in both cases revealed bilateral pulmonary
      infiltrates. Patient 1 required vasopressors for hypotension. Right heart
      catheterization ruled out fluid overload. Patient 2 remained hemodynamically
      stable. Both patients improved rapidly with continued respiratory support and
      were extubated within 48 h. CXR at this time showed clearing of infiltrates. In
      both cases a granulocyte antibody was identified in the plasma of a platelet
      donor supporting the diagnosis of TRALI. CONCLUSIONS: In suspected cases of
      TRALI. HLA and granulocyte antibody testing is indicated for the recipients and
      for donors of implicated components. Implicated donors need not be excluded from
      the donor pool, but can be used for fractionated plasma and plasma-free
      components.

PMID- 9269070
TI  - CD36 autoantibodies and thrombotic diathesis, thrombocytopenia and repeated early
      fetal losses.
AB  - BACKGROUND AND OBJECTIVES: Autoantibodies to CD36, a platelet glycoprotein, have
      been found in patients with thrombotic thrombocytopenic purpura, and in those
      with lupus-like anticoagulant with thrombotic complications. MATERIALS AND
      METHODS: Conventional hematologic and laboratory methods were used. The patient
      was a pregnant woman, who had had two early fetal losses separated by a normal
      offspring. Despite severe thrombocytopenia, she was asymptomatic. RESULTS:
      Serological investigations were strongly suggestive of CD36 autoantibodies.
      Neither clinical nor laboratory data were typical of those usually associated
      with cd36 autoantibodies, namely thrombotic thrombocytopenic purpura (TTP),
      systemic lupus erythematosis (SLE), or prothrombotic compliance. Prophylaxis with
      salicylates and prednisone was started at the 8th week of gestation, and an
      offspring with mild thrombocytopenia was delivered by cesarean section at the
      32nd week of gestation because of abruptio placentae. CONCLUSIONS: There may be a
      cause-and-effect relationship between early fetal losses and CD36 autoantibodies.

PMID- 9269071
TI  - Thrombocytopenia induced by vancomycin-dependent platelet antibody.
AB  - BACKGROUND AND OBJECTIVES: Many drugs are associated with thrombocytopenic
      purpura through immune-mediated platelet destruction. The case of a woman who
      suffered life-threatening thrombocytopenia during vancomycin treatment for
      Staphylococcus aureus septicemia is reported. MATERIALS AND METHODS: Conventional
      clinical and laboratory methods, including flow cytometry. RESULTS: After
      treatment of septicemia with vancomycin, severe thrombocytopenia and bleeding
      occurred, without detection of drug-dependent platelet antibodies (DDPA). This
      was followed by vegetative endocarditis, whereupon antibiotics were withdrawn so
      as to isolate the organism. The thrombocytopenia was corrected. On day 34,
      antibiotics including vancomycin were reinstituted, and three days later
      thrombocytopenia recurred. With a change in antibiotics, the platelet count
      corrected itself within four days. CONCLUSIONS: Vancomycin may induce potentially
      severe immunological thrombocytopenia.

PMID- 9269072
TI  - Consensus statement from the Consensus Conference on Unrelated-Donor Bone Marrow
      Transplants--29 and 30 October 1996. Their use in leukaemias and allied
      disorders.

PMID- 9269073
TI  - Seroprevalence of hepatitis B virus, hepatitis C virus, and human
      immunodeficiency virus antibodies in Turkish patients with hereditary coagulation
      factor deficiencies.

PMID- 9269074
TI  - Hepatitis E virus in haemodialysis.

PMID- 9269075
TI  - Altered filterability of fresh sickle cell trait donor blood.

PMID- 9269076
TI  - Post-irradiation plasma potassium and intra-uterine transfusion.

PMID- 9269077
TI  - A retrospective study of red cell maternal antibodies by chemiluminescence.

PMID- 9269078
TI  - A retrospective study of red cell maternal antibodies by chemiluminescence.

PMID- 9269079
TI  - Enhanced degradation of deethylatrazine in an atrazine-history soil of Iowa.
AB  - The degradation of deethylatrazine (DEA), a major metabolite of atrazine, was
      studied by using radiotracers in soils with two different atrazine histories. DEA
      degradation was enhanced in soils which had received long-term exposure to
      atrazine (atrazine-history soil) compared with soils that had not received long
      term atrazine exposure (no-history soil). After 60 days of incubation,
      mineralization of DEA to 14CO2 in the atrazine-history surface soil was twice
      that in the no-history surface soils, with 34% and 17% of the applied 14C-DEA as
      CO2, respectively. In surface soils, 25% of the applied 14C remained as DEA in
      the atrazine-history soil, compared with 35% in the no-history soil. Microbial
      plate counts indicated an increase in numbers of bacteria and fungi in soils
      incubated with DEA compared to control soils. No significant difference in total
      microbial respiration was seen among atrazine-history and no-history soils
      incubated with DEA, but DEA-treated soils had greater microbial respiration than
      untreated control soils after 6 days. A 14C-most-probable-number procedure was
      used to enumerate specific DEA degraders. A greater number of DEA degraders were
      indicated in atrazine-history subsurface soil compared with all other soils in
      this study (p < 0.05). From this study, it appears that an increase in microbial
      activity contributes to decreased persistence and increased degradation of DEA in
      soils that have had long-term exposure to atrazine at field application rates,
      compared to soils with no long-term exposure. Decreased persistence of this major
      metabolite of atrazine in atrazine-history soils is important in that there will
      be less available for movement in surface runoffs.

PMID- 9269081
TI  - Acetochlor-a comparative study on parameters governing the potential for water
      pollution.
AB  - The leaching behaviour of the herbicide acetochlor [2-chloro-N-(2-ethyl-6
      methylphenyl)-N-(ethoxymethyl)acetamide] was determined as compared with two
      congener compounds, alachlor [2-chloro-N-(2,6-diethylphenyl)-N
      (methoxymethyl)acetamide] and metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N
      (2-methoxy-1-methylethyl)acetamid e]. The leaching profiles of the herbicides in
      columns with different types of soil and their capacity factors in reverse phase
      HPLC were compared. An approach for preliminary characteristic of the potential
      for water pollution of acetochlor is presented. The herbicide is classified as a
      leacher in soil and its potential for contamination of ground water is comparable
      with those of alachlor and metolachlor.

PMID- 9269080
TI  - Residue levels of pyrethrins and piperonyl butoxide in soil and runoff water.
AB  - Simultaneous analysis of pyrethrins (Py-I and Py-II) and piperonyl butoxide (PBO)
      in soil and runoff water samples following field application of a new pyrethrum
      formulation containing pyrethrins (Py's) and PBO is described. Residues of total
      Py's and PBO were extracted from soil samples using hexane-acetone (9:1). A solid
      phase extraction (SPE) column containing C18-octadecyl bonded silica was used to
      separate Py's and PBO residues from runoff water. Residues in soil and water were
      quantitated by high performance liquid chromatography (HPLC) equipped with C18
      column and a UV detector. Concentration of Py-II in soil was 100 times higher
      than that of Py-I 1 h following treatment and 9.6 times higher than Py-I in
      runoff surface water 11 days following treatment. Results indicated that Py's are
      non-persistent in soil (even though lipophillic) and water when applied at the
      recommended rate of 6 lbs (5.31 g A.I.) per acre. There was a consistent decrease
      in total Py's residues as time after spraying increased. Py's residues in soil
      decreased from 0.91 to 0.11 ppm 4 days following treatment and one month after
      treatment only 0.002 ppm were detected. The highest concentration of Py's in
      runoff water was 36.09 ng/liter following the first rainfall (11 days following
      treatment). PBO initial residues detected in soil samples were low (0.84
      microgram/g soil) while no residues of PBO were detected in runoff water.

PMID- 9269082
TI  - Evaluation of atrazine positive and false positive immunoassay detections in
      ground water.
AB  - False positive responses on an atrazine (6-chloro-N-ethyl-N'-(1-methylethyl)
      1,3,5-triazine-2,4-diamine) immunoassay kit were investigated to explain possible
      causes for these occurrences. Ground water samples were evaluated with the
      immunoassay kit and positive responses (> 0.20 microgram L-1) were confirmed
      using gas chromatography/mass spectrometry (GC/MS). Non-confirming samples (false
      positives) were analyzed for seven additional compounds on GC. Resulting GC/MS
      and GC analyses showed that 70% of the false positives could be attributed to two
      compounds. Prometon (6-methoxy-N,N'-bis(1-methylethyl)-1,3,5-triazine-2,4
      diamine) was responsible for the majority (64%) of the false positive responses
      The atrazine metabolite, deethylatrazine (2-chloro-4-amino-6-isopropylamino-1,3,5
      triazine), was responsible for the other 6% of the false positives measured.
      Unattributed false positives (30%) were probably due to an overestimation of
      pesticide concentrations in the kit's lower detection range.

PMID- 9269083
TI  - Topical application of synthetic pyrethroids to cattle as a source of persistent
      environmental contamination.
AB  - Following the application of permethrin or cyhalothrin to cattle for the control
      of ectoparasites, the occurrence and persistence of these chemicals was assessed
      on the animals and in their environment. The release of permethrin from ear tags
      containing 1 g of the drug on cattle was followed for 65 days and lead to
      concentrations of 5 to 35 micrograms of permethrin per gram of hair on the
      shoulders. On the flanks of the animals, the corresponding values were 10 times
      lower. Across the 1.5 acre pasture, high concentrations of permethrin were
      measured at various locations and long after treatment: 6 micrograms/g on bark of
      a birch after one week, 5 micrograms/g on a pole of the fence after two weeks, 1
      microgram/g in grass from a resting site of the animal after six weeks, and 0.5
      microgram/g in bark of a pine tree after three month and two weeks after the
      animals had left the pasture. In similar assays, cyhalothrin applied to milk cows
      as a pour-on preparation was monitored. One week following treatment with 0.2
      g/animal, hair cut from the shoulders contained 5 micrograms/g of the
      insecticide, which disappeared with a half-life of 12 days. Dust collected two
      weeks after the pour-on treatment from the milk barn where the cows were milked
      twice daily contained 47 micrograms/g of cyhalothrin, which disappeared with a
      half-life of 44 days. These results show that synthetic pyrethroids used on farm
      animals can be the source of widespread and persistent contamination.

PMID- 9269084
TI  - In vivo and in vitro effects of deltamethrin on cytochrome P450 monooxygenase
      activity in carp (Cyprinus carpio L) liver.
AB  - The in vivo and in vitro effects of the insecticide deltamethrin (DM) on hepatic
      cytochrome P450 (Cyt P450) monooxygenase were examined in adult carp. The in vivo
      experiments were carried out with 0.2 microgram/l DM at 20 degrees C. The changes
      in the hepatic microsomal Cyt P450 content and the Cyt P450-dependent
      monooxygenase activities were studied in DM-treated fish. Although there were no
      changes in the Cyt P450 content during the exposure time, after treatment for 24
      h all the investigated isoenzyme activities (para-nitrophenetole-O-deethylase, p
      NPOD; aminopyrene-N-demethylase, APND; ethylmorphine-N-demethylase, EMND; 7
      ethoxycoumarin-O-deethylase, ECOD; and ethoxyresorufin-O-deethylase, EROD) were
      significantly inhibited. After 72 h, all the activities were still lower than in
      the control animals. In vitro incubation of liver microsomes with DM led to a
      concentration-dependent decrease in total microsomal Cyt P450 content. A complete
      loss of Cyt P450 occurred after a 5-min incubation with 60 microM DM. The maximum
      in the difference spectra of microsomes was shifted to higher wavelength, showing
      the strong interaction of DM with Cyt P450. EROD and ECOD activities were
      inhibited by DM. The in vitro kinetic results on ECOD revealed that the
      inhibition was of non-competitive type, with K1 = 9.8 +/- 2.3 microM. This study
      indicates important biochemical effects of DM in fish liver, and suggests that
      exposure to DM may cause loss of the Cyt P450-dependent metabolism in fish.

PMID- 9269086
TI  - Combined mass spectrometric methods for the characterization of human hemoglobin
      variants localized within alpha T9 peptide: identification of Hb Villeurbanne
      alpha 89 (FG1) His-->Tyr.
AB  - Mutation-induced amino acid exchanges occurring on the large T9 peptide of the
      alpha-chain of human hemoglobin (residues 62-90) are difficult to identify.
      Despite their high m/z value (around m/z 3000), collision-induced dissociation
      spectra of liquid secondary ion mass spectrometrically generated protonated alpha
      T9 peptides were performed successfully. In parallel electrospray mass
      spectrometry (MS) was used both to measure the molecular mass of the intact
      proteins and to determine the number of protonatable sites in the alpha T9
      peptides. Peptide ladder sequencing using carboxypeptidase digestions and
      analysis of the truncated peptides by matrix-assisted laser desorption ionization
      time-of-flight MS confirmed the interpretation. This set of methods allowed the
      characterization of three hemoglobin variants, with amino acid exchanges located
      in the alpha T9 part of the sequence. Two of them, Hb Aztec [alpha 76(EF5) Met-
      >Thr] and Hb M-Iwate [alpha 87(F8) His-->Tyr] were already known. The third
      [alpha 89(FG1) His-->Tyr] was novel and named Hb Villeurbanne.

PMID- 9269085
TI  - Swine wastewater treatment by media filtration.
AB  - A media filter was constructed to treat swine wastewater after anaerobic lagoon
      treatment. The media filter consisted of a tank (1.5-m-diameter x 0.6-m-height)
      filled with marl gravel. The marl gravel had a carbonate content of 300 g kg-1.
      Gravel particle size distributions were 85 and 14% in the 4.7- to 12.7-mm and
      12.7- to 19-mm size classes, respectively. Pore space of the filtration unit was
      57%. Wastewater flow rate was 606 L m-2 d-1, and total Kjeldahl nitrogen (TKN)
      load was 198 g m-2 d-1. The media filter removed 54% of chemical oxygen demand
      (COD) content after one cycle, but increased cycling did not produce additional
      COD reduction. Total suspended solids (TSS) removal after one cycle was 50% of
      initial levels, and additional cycling reduced TSS levels at a much lower rate of
      7% per cycle. Removal efficiencies for total phosphorus (TP) ranged from 37% to
      52% (one to four cycles), but long-term phosphorus removal would be limited by
      the sorption capacity of the gravel. Up to 24% of TKN was converted to nitrate
      plus-nitrite-N (NO3+NO2-N). Effluents with high NO3+NO2-N levels can be treated
      further for denitrification with constructed wetlands or anaerobic lagoon. This
      is important in cases where land is limited for wastewater application.

PMID- 9269087
TI  - Analysis of epoxyeicosatrienoic and monohydroxyeicosatetraenoic acids esterified
      to phospholipids in human red blood cells by electrospray tandem mass
      spectrometry.
AB  - Electrospray ionization (ESI) and tandem mass spectrometry (MS/MS) were used to
      analyze epoxyeicosatrienoic acids (EETs) and monohydroxyeicosatetraenoic acids
      (HETEs) isolated from human red blood cell membranes following base hydrolysis.
      ESI results in the formation of an abundant isobaric carboxylate anion at m/z 319
      for both of these oxidized metabolites of arachidonic acid. The product ion
      spectra from the collision-induced dissociation of this carboxylate anion could
      be used to identify each of the isomeric eicosanoids from the unique fragment
      ions of each eicosanoid. The observed product ion spectra were identical with
      those previously obtained by fast atom bombardment ionization; however, ESI
      required less EET and HETE for analysis. Both EET and HETE phospholipids were
      present in human red blood cells (RBCs) and their abundance could be
      substantially increased by treatment under conditions that would induce free
      radical oxidation of membrane phospholipids. Following incubation of human RBCs
      with tert-butyl hydroperoxide (tBuOOH), phospholipids were extracted and purified
      by normal-phase high-performance liquid chromatography (HPLC) as to
      glycerophospholipid class containing ethanolamine (GPE), serine (GPS) and choline
      (GPC) as the polar head group. Each class of phospholipid was hydrolyzed to yield
      the free carboxylic acid prior to on-line HPLC/ESI-MS/MS analysis. The formation
      of oxidized arachidonic acid esterified to phospholipids in treated RBCs was
      found to increase significantly for both esterified EETs in GPE, GPS and GPC
      which increased 49-, 34- and 59-fold, respectively, and also for esterified HETEs
      in GPE, GPS and GPC which increased 3-, 4- and 11-fold, respectively, compared
      with untreated RBCs. These results provide the first characterization of EETs
      formed non-enzymatically as intact phospholipids in a lipid peroxidation model
      system.

PMID- 9269088
TI  - Human cryptosporidiosis: detection of specific antibodies in the serum by an
      indirect immunofluorescence.
AB  - Cryptosporidium sp., a coccidian parasite usually found in the faeces of cattle,
      has been recently implicated as an agent of human intestinal disease, mainly in
      immunocompromised patients. In the study realized, by an indirect
      immunofluorescence technique, specific immunoglobulins (IgG and IgM) have been
      demonstrated in human serum against Cryptosporidium oocysts. Purified oocysts
      were used as antigens in the indirect immunofluorescence assay. After analyzing
      this test in sera from selected groups of patients, the frequency of both
      specific IgG and IgM of immunocompetent children who were excreting oocysts in
      their faeces was 62% and in children with negative excretion of oocytes was 20%
      and 40%, respectively. In adults infected with the human immunodeficiency virus
      (HIV) and who were excreting Cryptosporidium in their stools, the frequency was
      57% for IgG but only 2% for IgM. Twenty three percent of immunocompromised adults
      with not determined excretion of oocysts in their stools had anti-Cryptosporidium
      IgG in their sera. Children infected with human immunodeficiency virus had no IgM
      and only 14% had IgG detectable in their sera. The indirect immunofluorescence
      assay, when used with other parasitological techniques appears to be useful for
      retrospective population studies and for diagnosis of acute infection. The
      humoral immune response of HIV positive patients to this protozoan agent needs
      clarification.

PMID- 9269089
TI  - [Evolution of neonatal mortality in the State of Rio de Janeiro, Brazil, from
      1979 to 1993. 1--Analysis by age-group according to area of residence].
AB  - The behavior of the infant mortality rate in the State of Rio de Janeiro, Brazil,
      from 1979 to 1993, is analysed. The annual rate of variation, calculated as the
      slope of an exponential regression model, indicates an overall decreasing trend
      of approximately 5% per year. Although the neonatal component is also decreasing,
      the annual rate of variation is much lower, of only 2.4% per year, and is even
      lower (1.6%) when deaths caused by malnutrition or infectious diseases are not
      taken into account. Examining date by region of residence, the area composed of
      the counties located outside the metropolitan region-called the "Interior"
      presents the worst performance. When mortality rates are analysed by age-group an
      interesting pattern is found: the shorter the time of life the lower the value of
      the rate variation. In contrast to what is found in developed countries, where
      care is more intensive for newborn children, the infant mortality rate in Rio de
      Janeiro State decreases less as the number of hours of life approaches the
      delivery; for the groups of deaths that occurred within the first of life, an
      increasing trend is found in all of the residential regions considered in this
      study. To face this situation, it is necessary to reaffirm the priorities of the
      health services, not only in respect to the improvement of the quality of medical
      assistance but also to the development of strategies for the epidemiological
      monitoring of the Brazilian situation.

PMID- 9269090
TI  - [Prevalence of dental caries in children from 0 to 6 years old attending nursery:
      the influence of socioeconomic factors].
AB  - Oral health condition in samples of children from zero to six years old, examined
      in day nurseries for children from Bauru and S. Paulo County (Brazil) by the
      caries indicator in primary dentition-dmfs, is assessed. The first group did not
      receive oral health care where any as the second group received the standard oral
      care provided by the institution. Variables related to way of life and their
      relationship to the presence of caries were evaluated. Multiple regression
      analysis showed a statistically significant association of age and frequency of
      dental visits with the prevalence of dental caries (p < 0.05). The data also
      showed that 23.3% of the children from Bauru, and 9.3% of those from S. Paulo
      were free of caries, numbers that are very far from the 50% proposed by WHO for
      the year 2000. The overall prevalence of dental caries was greater for the Bauru
      group than for the S. Paulo group; however, statistical significance was only
      found in the 3-4 age-group (p < 0.05). Sex differences in the occurrence of
      dental caries were not statistically significant.

PMID- 9269091
TI  - [A computer software system for dental caries rates: databases and statistical
      analysis].
AB  - A computer software system developed ICADAPLUS, is presented in order to create
      and tabulate data bases, calculate the DMF rate, perform statistical comparison
      of two populations, and calculate confidence intervals. The system offers a
      simplified method for health services in the area of dentistry, using dental
      records to carry out epidemiological surveys of tooth decay. The system's main
      feature is that it does not require specialists either in the area of dentistry
      or computing, demanding of the user only basic data-entry typing skills, since it
      presents simple menus, and standardized reports, with no possibility of error.
      The system comprises four steps: Data-entry, Processing, Reports and Utilities.
      In Data-entry the regions, towns and institutions supplying the data are
      initially registered, once only. Each record receives a code number, and it is
      this code which is available to the user through a Function Key, by means of
      which the code is transferred to the desired data field. Furthermore, there is a
      choice of type of dental chart: Klein and Palmer's DMF; the DMF proposed by the
      WHO; Klein, Palmer and Knutson's DMF surfaces; or Gruebbel's def. It is possible
      to include, alter and exclude records in each option. In Processing, it is
      necessary, first of all, to organise the indexes, totalize the data, and remit
      them to the data base, where no further alteration or exclusion occurs. From this
      stage on, reports can be prepared from the proposed indexes, grouped according to
      age, or age and gender. The system was validated by comparison with other
      methods. This comparison justifies the recommendation of its implementation.

PMID- 9269092
TI  - [Occurrence of American cutaneous leishmaniasis by remote sensing satellite
      imagery in an urban area of Southeastern Brazil].
AB  - The areas in which american cutaneous leishmaniasis was reported in 1993 and 1994
      for the region around the town of Lagoinha, S. Paulo, Brazil (Lat 23 degrees 05'
      S; Long 45 degrees 11w) were plotted on a TM-LANDSAT image. The false color
      composition of bands 3, 4 and 5 made it possible to identify the relevant
      vegetation (shrubs and trees) within the boundaries of those areas and in their
      proximity, where they were found at a distance of not more than about 250 meters
      from the perimeter of each area. The use of means capable of presenting a larger
      view of a geographical area made the advantages of remote satellite sensing as a
      tool for the study of this endemic disease clear.

PMID- 9269093
TI  - [Population statistics of Triatoma sordida Stal 1859 (Hemiptera:Reduviidae) in
      experimental conditions].
AB  - Four cohorts of 100 Triatoma sordida eggs were reared under standard laboratory
      conditions (28 degrees C, 63% R.H.) and fed weekly on hens during 40 minutes. The
      numbers of dead insects, moults and eggs laid were recorded weekly. A constant
      survival value was observed without any important peaks in the four cohorts. Life
      expectancy was 37.4 weeks for males and 36.8 weeks for females. The average
      generation time was 61.7 weeks. The average net reproduction rate suggests that
      this population would increase 143.2 times during each generation. The average
      intrinsic rate of natural increase was 0.082 per individual per week. The highest
      reproductive value was observed 3 weeks after entering the adult stage. The age
      structure, assuming stable age distribution, would be 32% eggs, 26% of first
      instar nymphs, 19% of second instar nymphs, 13% of third instar nymphs, 6% of
      fourth instar nymphs, 3% of fifth instar nymphs and 1% of adults. Our results
      suggest that this species behaves as a k-strategist under experimental
      conditions.

PMID- 9269094
TI  - [Difficulties encountered in gathering information on illegal abortion in the
      population of women].
AB  - Any attempt to study the practice of illegal abortion faces the problem of asking
      women about a delicate, sensitive issue that has many implications. This may make
      it difficult to obtain truthful information on the subject. Results related to
      methodological aspects are emphasized and their possible association with
      variables included in a cross-sectional study carried out among 1,955 women, of
      15 to 49 years of age is analysed. The frequency and conditions under which
      induced abortion was performed in a region of S. Paulo State are investigated.
      The women were interviewed at home using a pre-tested, structured questionnaire.
      Most of the women interviewed declared they had never had an abortion nor had
      they thought of having one, and four percent referred to having had an induced
      abortion. However, another 16.7 percent said that they had taken tea or medicine
      at least once to bring on their menses. In this group, most of the women who
      thought they were pregnant at that time said they had had never an abortion, in
      spite of having bled after drinking tea or medicine. The results lead to the
      conclusion that women tend no omit information on the practice of abortion when
      questioned directly. This is especially true of those who use oral means to bring
      on their menses and who seemed not to consider this a way of inducing an
      abortion.

PMID- 9269095
TI  - [Contraceptive choices and experience of sexuality: a comparison between
      sterilized and non-sterilized women in a metropolitan area of southeastern
      Brazil].
AB  - A cross sectional study involving 357 women, 174 of them sterilized and 183 non
      sterilized, with a view to comparing their sexual and reproductive behaviour, was
      undertaken. The questionnaire was based on previous focus group discussions with
      both women and men, to find out the best way to approach related questions. The
      results show that sterilized women-who are older and more often have steady
      partnerships than non-sterilized women-fulfil traditional gender roles more
      closely than the others. Furthermore, no sterilized woman had used the condom in
      the month prior to the interview. It is suggested that public messages for the
      prevention of the spread of the HIV, sexually-transmissible disease and cervical
      cancer should target women who have been sterilized for the purpose of increasing
      the use of the condom in accordance with specific strategies.

PMID- 9269096
TI  - [Evaluation of the protection received by a BC antimeningococcal vaccine in the
      State of Santa Catarina, Brazil, 1990/92].
AB  - Results of the evaluation of the anti-meningococcal BC Cuban vaccine based on
      routine epidemiological surveillance information of meningitis for the years 1990
      to 1992, following mass-vaccination of 232,022 children aged between 3 months and
      7 years in 1989/90 during an epidemic of serogroup B meningococcal disease in the
      State of Santa Catarina, Brazil, are presented. The protective efficacy of the
      vaccine was calculated from the incidence rates for the cohort of vaccinated and
      non-vaccinated children in 20 municipalities. Main results for cases confirmed by
      bacteriological tests were 59% (CI 95%: 23 to 78%) for children aged under 4
      years and 78% (CI 95%: 54 to 90%) for children aged 4 to 7 years. Eighty-six
      percent of cases serogrouped (n = 29) were B, and in these cases efficacy
      increased to 66% (< 4 years) and 88% (4-7 years), but at 95% CI were wider. The
      protective efficacy based on death rates from the disease in children < 4 years
      was 76% (CI 95%: 41 to 91%). There was no evidence of decreasing protective
      efficacy in the three year follow-up, as shown by the yearly estimates. An
      interesting hypothesis arising from the findings is that the lower protective
      efficacy for children aged < 4 years, observed in studies in which only cases
      confirmed by laboratory tests are analysed, could be due to a selective effect of
      this procedure. More severe cases die shortly after the onset of the disease,
      often before medical care is provided. On the other hand, the attenuation of the
      disease by vaccination gives a better chance for medical intervention and
      collection of samples for laboratory analysis. Finally, the authors support the
      use of the vaccine in epidemics of serogroup B meningococcal disease. They also
      suggest that three, rather than two doses of vaccine should be tested in children
      under 2 years of age to further increase its efficacy.

PMID- 9269097
TI  - [Dose-response effect of risk factors for ischemic heart disease].
AB  - Several authors have reported hypertension, smoking and hypercholesterolemia as
      independent risk factors to ischaemic heart disease (IHD). However few of them
      have investigated the existence of a linear gradient related to the levels of
      these exposures and IHD. The effect of different levels of these exposures and
      IHD after adjusting for known confounders of effect, is assessed. The project was
      designed as a case-control study and the data were collected over one year from
      March/93 to February/94. The sample was composed of a total of 833 individuals of
      both genders aged 30-69 living in the city of S. Paulo, SP (Brazil), 280 of whom
      were compared with 553 controls (285 neighbourhood controls and 268 hospital
      controls). Logistic regression was the statistical method wold for the analysis
      of the data. The results showed a linear gradient for known duration of
      hypertension and daily number of cigarettes consumed. Although the variables
      duration of hypercholesterolemia and duration of the habit smoking presented
      statistically significant odds ratio in the respective strata there was no
      indication of a linear gradient. Some methodological issues are presented to
      explain this absence of a linear gradient for known duration of
      hypercholesterolemia and duration of the smoking habit. It is concluded that the
      dose response effect detected for known duration of hypertension and daily number
      of cigarettes consumed were independent of the presence of major risk factors
      ischaemic heart disease.

PMID- 9269098
TI  - [Evaluation of the use of the International Classification of Diseases for the
      codification of AIDS].
AB  - The International Classification of Diseases (ICD) provides codes for all
      conditions and permits international comparisons of morbidity and mortality.
      Because it has to be used all over the world its codes are not always perfectly
      appropriate. There are revisions from time to time to bring up-to-date the
      classification. This has happened with AIDS, included in the chapter of
      infectious diseases in the last revision, ICD-10. The use of ICD-10 AIDS codes is
      here appraised. All surveillance report forms of one specialized hospital in
      infectious diseases, notified in 1994, have been codified, but it was found that
      many diagnoses could not be codified in accordance with a single ICD-10 AIDS
      code.

PMID- 9269099
TI  - Outbreak of vampire bat biting in a Venezuelan village.
AB  - An outbreak of 154 cases of vampire bat biting in a four-month period in the gold
      mine of Payapal, a Venezuelan village, is reported. All patients were bitten
      during the night and the most bites were on their toes. No complication
      attributed to the bite was reported. Diagnoses of rabies virus made by means of
      immunofluorescence were negative. A possible reason for this outbreak may been
      the development of mining areas, with the inhabitants providing an alternative
      food source for the bats.

PMID- 9269101
TI  - The treatment and prevention of acute ischemic stroke.

PMID- 9269100
TI  - [Demographic profile and health conditions of the elderly in a community in an
      urban area of southeastern Brazil].
AB  - Some specific characteristics of the aging of the Brazilian population in
      different areas, states and communities all over the country, have shown
      significant variations. Historical series of demographic and health indicators
      for the population in their sixties and over in Brazil, state of S. Paulo and in
      the municipal district of Araraquara are listed as follows: level of education
      and urban population growth rate, income distribution, mortality rates and main
      causes of death. In 1991 the aged constituted were 7.8% of the Brazilian
      population and 9.7% in Araraquara community. The elderly population (of 70 years
      of aged and above) as a proportion of the whole, has increased and already stands
      for 40%. The same trend holds good for both the proportion of aged within the
      urban population and their level of education which increased to 90% in 1991. The
      main causes of death are chronic degenerative diseases which have replaced the
      infectious illness: first, the diseases of the circulatory system (which account
      for more than 40% of all deaths) and the neoplasms (which let to 15% of the
      deaths). On the basis of these health and demographic data relating to people of
      60 years of age and over, this study suggests some procedures for the improvement
      of the quality of the assistance given to the target population: a) the
      assistance give to the aged should be improved by providing gerontological
      training for general physicians and nurses, both of public and private clinics;
      b) the already existing educational activities for the aged, for health workers
      and for teachers of secondary education should be further developed; c) the
      number of day-hospitals should be increased for the purpose of avoiding
      unnecessary confinement so as maintain the low rate of institutionalization in
      homes for the elderly (0.7% in Araraquara). It is reported that at least 35% of
      the aged population in this area is entitled to private health assistance, which
      brings out the importance of including such services in the local health programs
      for this group.

PMID- 9269102
TI  - Laparoscopic cholecystectomy in children and adolescents.
AB  - During the period between August 1991 and November 1995, seven patients under age
      17 were submitted to videolaparoscopic cholecystectomy (LC). Two were males and
      five females with ages ranging from 12 to 16 years (mean 13.8 years). The
      diagnosis of chronic cholecystitis with gallstones was made by the clinical
      history and physical and ultrasonographic examinations. There was no evidence of
      an association with hemolytic diseases, familial hyperlipidemia or Glucose-6
      phosphate dehydrogenase (G6PD) deficiency. The surgery was performed under
      general anesthesia and the abdomen approached by four ports: a 10 mm umbilical
      incision, a 5 mm cystic, a 5 mm one at the xiphoid appendix and a 10 mm one at
      the left lateral margin of the left rectus abdominal muscle between the umbilical
      scar and the xiphoid appendix. Operative time averaged 120 minutes (105-150 min).
      One case required conversion to laparotomic approach because of Mirizzi's
      Syndrome, which was diagnosed by intraoperative cholangiography performed in all
      cases. There were no deaths or major postoperative complications. Hospital stays
      ranged from 1-3 days in the six patients submitted to LC. Thus LC in children can
      be considered a good method, requiring only more care regarding the use of proper
      equipment, complete and careful dissection of the biliary hilus, and
      intraoperative cholangiography. The latter is indispensable, as these children
      can present a higher rate of anatomic anomalies. The advantages of this
      techniques include a less painful postoperative period with a faster recovery,
      and it is especially recommended in children, who are less tolerant to physical
      restriction and pain than adults.

PMID- 9269103
TI  - Smoking and its relation to the histological type, survival, and prognosis among
      patients with primary lung cancer.
AB  - The frequency of smoking among patients with primary lung cancer diagnoses
      admitted to the Hospital de Clinicas de Porto Alegre (HCPA) during the 1980's was
      investigated. The objective of this study was to analyze cigarette consumption
      patterns through the number of cigarettes smoked per day and the age at which
      smoking began, correlating this data to the overall survival rate and
      histological type of the lung cancer. METHODS: This retrospective study analyzed
      patients with primary lung cancer diagnosed at the HCPA between January 1980 and
      December 1989. All patients considered underwent follow-up for at least three
      years. Patient information was obtained either from the hospital's records or by
      contacting patients via letter or phone. RESULTS: More than 90 percent of the
      patients were smokers or had smoked previously; most had started smoking before
      the age of 20. The overall 24-month survival rate after diagnosis varied
      depending on whether the patient had smoked less than 40 cigarettes per day or
      not. The percentage of smokers and non-smokers was established for each
      histological type, with the bronchoalveolar adenocarcinoma type showing the
      highest percentage of non-smokers (40 percent). CONCLUSION: The overall survival
      rates of patients with lung cancer was related to the number of cigarettes
      smoked, and not to the fact of the patient having smoked or not. The number of
      smokers among patients with lung cancer was not so high only for the
      bronchoalveolar adenocarcinoma histological type.

PMID- 9269104
TI  - Clinical and manometric postoperative evaluation of posterior sagital
      anorectoplasty (PSARP) in patients with upper and intermediate anorectal
      malformations.
AB  - PSARP is currently the most widely-used surgical technique for surgical
      correction of high and intermediary anorectal malformations, but there is much
      controversy in the literature about the postoperative evaluation of these cases.
      We studied 27 cases of anorectal malformations operated with PSARP from clinical
      and manometric aspects in order to analyze: 1) fecal continence; 2) the
      relationship between fecal continence and the associated sacral anomalies and; 3)
      the relationship between the postoperative manometric evaluation and fecal
      continence. From the analysis of 27 cases of high and intermediary anorectal
      malformations, we concluded that: 1) fecal continence was achieved in 48.14
      percent of the cases; partial fecal continence in 25.92 percent; and fecal
      incontinence in 25.92 percent of the cases; 2) the presence of fecal incontinence
      was directly related to the association of sacral anomalies and; 3) anorectal
      manometry is a useful test to evaluate the patients operated by PSARP, due to the
      existence of a relationship between the manometric results and the degree of
      fecal continence.

PMID- 9269106
TI  - Chordoma: retrospective analysis of 24 cases.
AB  - INTRODUCTION: Chordoma is a rare and slow-growing tumor, with local
      aggressiveness and preferential localization in the vertebral column. OBJECTIVE:
      The main objective of this study is to evaluate natural history and results of
      treatment of chordomas. METHODOLOGY: This is a retrospective study from 1953 to
      1993. MATERIAL AND METHODS: The age ranged from 2 to 86 years (mean = 34.5).
      Twelve patients were male and 12 female. The localization of the tumor was: 20 in
      the sacral region, 3 in head and neck and one out of the spine. RESULTS: The
      treatment, alone or combined, was surgery, radiation therapy and chemotherapy.
      The survival rate for patients with lesions in the sacrum ranged from 4 to 119
      months, since the date of the symptoms. The 5-year overall survival was 4.2%.
      CONCLUSION: Chordoma is a rare and slow growing tumor, with a very difficult
      approach by surgery due to its preferential location in the sacrum and poor
      therapeutic results with radiation therapy or chemotherapy, mainly in patients
      with advanced disease.

PMID- 9269105
TI  - Extrahepatic bile ducts injury: a report on 14 cases.
AB  - Traumatic injuries of the extrahepatic biliary tract are infrequent, occurring in
      approximately 0.5% of all patients with blunt and penetrating abdominal trauma.
      The incidence of this injury due to blunt abdominal trauma is rare. This study
      reviewed patients with injuries of the extrahepatic biliary tract due to
      abdominal trauma over a 6-year period to determine the incidence, trauma scores,
      associated injuries, surgical treatment performed, complications and mortality
      rate. We report our experience with 14 patients with extrahepatic biliary tract
      trauma. A review of the literature and the discussion about the management are
      presented.

PMID- 9269107
TI  - Stercoral perforation of the normal colon: report of five cases.
AB  - A series of five consecutive patients with stercoral perforation of the colon is
      presented. Four of the patients had free perforation and one had an abscess
      between the splenic flexure, spleen and surrounding organs, a yet unreported
      entity. All patients underwent emergency surgery including laparostomy with
      repeated explorations and lavages in two of them. The ethiology, pathophysiology
      and treatment of the condition are updated. A graphic algorithm for decision
      making in appropriately dealing with stercoral perforation of the colon is
      proposed.

PMID- 9269109
TI  - Classification of total knee prostheses.

PMID- 9269108
TI  - Re: Acetabular rim pathology secondary to congenital hip dysplasia in the adult.
      A radiographic study.

PMID- 9269110
TI  - Intraoperative pathologic consultation (IOC) for tumors of the bone.
AB  - When combining clinical examination, laboratory information and noninvasive
      imaging studies the differential diagnosis of bone lesions is narrowed. For those
      who are not experts in the field the major purpose of the IOC is to insure that
      adequate tissue has been obtained and to triage the tissue in the process
      preparing imprints, whenever possible; fixing some tissue for possible electron
      microscopic review; placing some tissue in B5 fixative for better cytologic
      detail; and to save some undecalcified tumor tissue in formalin in case
      immunostaining procedures are required. Most community pathologists should not be
      attempt to make an absolute diagnosis at the time of IOC, in many cases. The
      surgeon should always be warned that despite seeming benignancy 50% of primary
      bone tumors are malignant, that benign lesions can prove to be low grade sarcomas
      after full review, and vice versa that occasional cellular, "pleomorphic" lesions
      can be benign (aneurysmal bone cyst, early reparative and pseudosarcomatous
      lesions). Following review of the permanent sections, and other appropriate
      procedures an accurate diagnose is possible in the majority of cases. If the
      diagnosis is particularly difficult or questionable the above materials can be
      sent to a bone tumor specialist.

PMID- 9269111
TI  - The external fixator for the treatment of wrist fractures.
AB  - The authors present 15 unstable fractures of the wrist treated by external
      fixation. The fractures were classified based on the AO system, while results
      were evaluated clinically (Gartland and Werley method modified by Sarmientio) and
      radiographically. In two cases stabilization with metal wiring was used in
      addition to external fixation. Results were excellent in 4 cases, good in 9,
      unsatisfactory in 2 (1 fair, 1 poor). Intraoperative complications included a
      compound fracture of the second metacarpus, and late complications included a
      case of algodystrophy.

PMID- 9269112
TI  - Two compression rods to treat unstable lesions of the pelvic ring.
AB  - The authors report 7 cases involving the surgical treatment of unstable pelvic
      ring fractures (Malgaigne type) using two compression bars, as described by Tile.
      The method was used only in cases where x-ray examination and CT scan revealed
      that the posterior branch of the fracture was located at the very medial aspect
      of the sacrum (fracture through the sacral foramina or even medial to the sacral
      foramina), and therefore could not be stabilized by using other devices.

PMID- 9269113
TI  - The long gamma nail: indications and results.
AB  - The authors report their experience concerning the use of the long gamma nail in
      18 cases with the following indications: double fractures of the proximal end and
      the diaphysis of the femur; subtrochanteric fractures and of the diaphysis with
      severe lesion of the medial cortical bone; subtrochanteric pathologic fractures.
      All of the fractures except one consolidated within 6 months and weight-bearing
      was allowed early. Breakage of the means of synthesis was the only major
      complication observed. The long gamma nail has proven to be an irreplaceable
      method for the treatment of associated fractures of the proximal end and of the
      femoral diaphysis.

PMID- 9269115
TI  - The biological problems of total hip arthroplasty.
AB  - Biological phenomena are the principal agents in triggering hip prosthesis
      aseptic loosening. The authors report the results of "in vivo" and "in vitro" and
      Raman-laser experimental tests, which confirm the validity of the ceramic-ceramic
      combination in relation to the amount of wear and biocompatibility of friction
      materials.

PMID- 9269114
TI  - Bankart-Delitala surgery in the treatment of recurrent anterior dislocation of
      the shoulder.
AB  - The study analyzes the results obtained when Bankart-Delitala surgery was used to
      treat recurrent anterior dislocation of the shoulder. A group of 30 patients were
      submitted to clinical and functional follow-up based on the Rowe system; 15 of
      the patients also underwent isokinetic testing. The data obtained were
      interpreted based on the Rowe system, but also analytically and statistically.
      The authors conclude that Bankart-Delitala surgery constitutes an effective
      surgical option in the treatment of recurrent anterior dislocation of the
      shoulder.

PMID- 9269116
TI  - Spontaneous recurrent hemarthrosis of the knee with lesion of the lateral
      meniscus and arthrosis of the lateral compartment.
AB  - One of the possible atraumatic causes of recurring hemarthrosis of the knee is
      constituted by the association of a lesion of the lateral meniscus with severe
      gonarthrosis of the lateral compartment. In the case described we were able to
      determine the cause of frequent bleeding (12 times in 15 months) in a traction
      caused by the injured meniscal tissue on the terminal branches of the geniculated
      arteries in the area of the popliteal hiatus. Thus, this clinical manifestation
      cannot be attributed to a synovial pathology. Total arthroscopic meniscectomy
      solved the problem.

PMID- 9269117
TI  - Synovial chondromatosis of the shoulder. A review of the literature and
      description of a clinical case.
AB  - The paper provides a brief review of synovial chondromatosis of the shoulder,
      with the description of a clinical case as an example. Surgical treatment
      constituted by removal of the free intraarticular bodies does not always result
      in radical synovectomy because of the complexity of the anatomy in that region.

PMID- 9269119
TI  - Pathologic fracture on bone cyst of the femoral neck treated by external fixator.
      Description of one case.
AB  - In 1993 a patient aged 16 years affected with pathologic fracture on bone cyst of
      the proximal femur came to our observation. The fracture and the cyst healed in
      10 months after treatment using an external fixator and autoplastic bone grafts.

PMID- 9269118
TI  - Diastematomyelia in congenital scoliosis. A review of the literature and
      description of one clinical case.
AB  - The authors present a case of diastematomyelia, a malformation of the neurospinal
      axis, frequently associated with congenital vertebral deformities. Often
      asymptomatic, its site different from that of the vertebral deformity, it may go
      unrecognized if specific imaging diagnosis is not used, thus exposing the patient
      who is then submitted to surgery for the correction of vertebral deformity to a
      high risk of neurological complications.

PMID- 9269121
TI  - Psychotherapy research: linking efficacy to policy and practice.

PMID- 9269120
TI  - The efficacy of psychotherapy.

PMID- 9269122
TI  - [Psychiatric services, social cooperation, voluntary activities. New
      relationships for new strategies].
AB  - OBJECTIVE: Eighteen years after the 1978 reform law no. 180, psychiatric services
      have to find new roles and goals in the social arena, in order to continue to
      effectively pursue the improvement of mental health in the community. The aim of
      the present paper is to show some theoretical and practical elements that could
      stimulate in the psychiatric services a deep consideration about the relationship
      between psychiatric services and "private social" bodies, particularly social co
      operatives and voluntary organisations. METHOD: The elements shown in this study
      come from an analysis: a) of the literature about the crisis factors of the
      Italian welfare state, particularly in the Public Health Service and in the
      social assistance; b) of the literature about the development of the "private
      social" and about the relationship with the public services; c) of national and
      regional laws, particularly of Veneto region; d) of the present experiences in
      South Verona Psychiatric Service. RESULTS: The crisis of the traditional welfare
      state, the emergence in large sectors of general population of needs related to
      social fragmentation and relational impoverishment, the aspiration of a great
      number of individuals excluded from society to benefit of the right to full
      citizenship, all this urgently questions the traditional roles and
      responsibilities, the organisation, operational modalities, and the community
      orientation of existing health and human services. Within this framework, the
      relationship between psychiatric services (or, broadly speaking, public services
      in general) and "private social" bodies, particularly social co-operatives and
      voluntary organisations, has become part of a foreseeing, strategic new awareness
      of mental health workers. CONCLUSION: A shift from a relationship of mutual
      exploitation between organisations, to one of co-operation between them, each
      considering the other as an equal partner, may be a critical step forward a new
      model of welfare. This, in turn, would hopefully meet the needs for health of the
      population in terms of efficiency, quality, relevance and consideration of the
      users' resources and social competencies.

PMID- 9269124
TI  - Polycystic ovarian syndrome and pregnancy.
AB  - The paper describes a case of polycystic ovarian syndrome (PCOS) characterised by
      normal blood insulin levels and LH hypersecretion which explains the
      etiopathogenesis of the two voluminous ovarian masses originating from micro
      cysts existing prior to pregnancy and undergoing abnormal growth during gestation
      owing to stimulation by beta-HCG (beta human chorionic gonadotropin). The ability
      of HCG ti stimulate ovarian steroidogenesis in pregnancy can result in enhanced
      testosterone and androstenedione levels. Our findings, like those of another
      recent report, emphasise the correlation between beta-HCG levels and testosterone
      values; the quantitative increase in beta-HCG probably plays an essential part in
      determining the abnormal development of the ovarian cysts, which remained
      morphologically unchanged up to delivery. Our patient's virilisation is explained
      by the increase in total testosterone in circulation. Fetal virilisation cannot
      be assessed in this patient because the mother gave birth to a male.

PMID- 9269123
TI  - Stimulatory effect of intracerebroventricular met- and leu-enkephalin on
      corticosterone secretion in rats.
AB  - The significance of enkephalins for the function of the hypothalamic-pituitary
      adrenal (HPA) axis, in spite of many efforts, is still elusive. We investigated
      the effect of leucine- and methionine-enkephalin on the HPA activity in conscious
      rats. These enkephalins, given intracerebroventricularly (i.c.v.) increased dose
      dependently the activity of the HPA axis, measured indirectly through serum
      corticosterone levels. On a molar basis, leu-enkephalin exerted a stronger effect
      that met-enkephalin. Naloxone, an opioid receptor antagonist, given i.c.v. prior
      to enkephalins almost abolished the corticosterone response to met-enkephalin and
      significantly impaired the response to leu-enkephalin. Prazosin, an alpha 1
      adrenergic antagonist, considerably reduced the increase in serum corticosterone
      levels induced by both enkephalins. Pretreatment of rats with yohimbine, an alpha
      2-adrenergic antagonist, also considerably reduced the corticosterone response to
      met-enkephalin and significantly diminished the response induced by leu
      enkephalin. Naloxone and yohimbine inhibited to the same extent the
      corticosterone response to met- and leu-enkephalin. This suggests an interaction
      between presynaptic opioid and alpha 2-receptors in regulation of the HPA
      function. Propranolol, a beta-adrenergic antagonist, given i.c.v. did not alter
      the corticosterone levels raised by met- and leu-enkephalin. These results
      indicate that both met- and leu-enkephalin increase the activity of the HPA axis
      in rats and both central opioid and adrenergic alpha-receptors are involved in
      this stimulation.

PMID- 9269125
TI  - Anthelmintic efficacy of ivermectin against Syngamus trachea and Capillaria spp.
      in pheasant.
AB  - Ivermectin (IVM) was perorally administered in dosage schemes 1 x 0.8 mg/kg of
      body weight (b.w.), 1 x 1.6 mg/kg h.w., 3 x 0.8 mg/kg b.w., and 3 x 1.6 mg/kg
      b.w. to pheasants infected by Syngamus trachea and Capillaria spp. The samples of
      faeces were coprologically examined. The clinical state of pheasant was
      controlled. In all of the used therapeutical schemes the helminthostatic or
      partially helminthocide effect against adults of worms was reached. The clinical
      signs of helmithoses were reduced only. IVM in tested doses is not possible to
      recommend as an effective drug of pheasant syngamosis and capillariosis.

PMID- 9269126
TI  - Survival of model helminth eggs and larvae (Ascaris suum, Oesophagostomum sp.) in
      the ensilaging process.
AB  - Ascaris suum nonembryonated eggs remained viable for the most part even after 42
      days of ensilaging. At the end of the anaerobic fermentation, mean of damaged
      eggs was 15.2 +/- 4.02 (min. 11, max. 21), 32.9%. Conversely, the viability of
      Oesophagostomum sp. nonembryonated eggs and infective L3 larvae was reduced-eggs:
      mean number 23.6 +/- 3.64 (min. 20. max. 28) specimens (93.3%), L3 larvae: mean
      number 24.2 +/- 4.38 (min. 19, max. 28) specimens (96.7%), during the period of
      study (42 days). Control group of the same helminth propagative stages, was kept
      under optimum aerobic conditions. After 42 days of exposition, 9.0 +/- 3.46 (min.
      5, max. 11) nonembryonated Ascaris suum eggs (12.9%), 17.33 +/- 2.51 (min. 15,
      max. 20) Oesophagostomum sp. eggs (36.4%) and 3.66 +/- 1.15 (min. 3, max. 5)
      Oesophagostomum sp. larvae L3 (6.3%) were damaged on average. Helminth eggs,
      thick-walled and more resistant to the environment in particular, are able to
      survive the anaerobic process of ensilaging. To protect animals against parasitic
      diseases, it is necessary to consider the epidemiological hazard of silages and
      silage juices, which are potentially contaminated by helminth propagative stages.
      Silages and silage juices under certain conditions may become harmful to
      polygastric animals.

PMID- 9269127
TI  - Oxidative and antioxidative activity in the patients with disseminated
      demyelinating disease of central nervous system.
AB  - Considering the basic pathologic process and current knowledge of the
      physiopathologic mechanisms in the active phase of disseminated demyelinating
      disease of central nervous system, the increase of oxidative processes was
      assumed in the patients with that disease in the phase of clinical impairment.
      The aim of the research was to study some indices of oxidative processes and
      activity of antioxidative enzymes in such patients. The research was performed on
      blood samples (erythrocyte hemolysate and plasma) and cerebrospinal fluid of 30
      patients with disseminated demyelinating disease of central nervous system during
      the clinical impairment and during the increase of immunologic activity in
      intrathecal space. The patients were of younger age, in the acute phase or with
      the shorter disease duration (up to 3 years). Control group was formed of 12
      patients examined for lesions of intervertebral disks in lumbosacral region. The
      research results demonstrated the increase of superoxide anion production, the
      elevation of lipid peroxidation followed by the increase of superoxide dismutase
      and glutathione reductase activation. It was concluded that the signs of
      simultaneous increase of oxidative processes and antioxidative activity, but also
      the oxidative impairment of lipid structures existed in the studied patients
      during the acute phase.

PMID- 9269133
TI  - Effects of grades and other loads on on-road emissions of hydrocarbons and carbon
      monoxide.
AB  - This project was developed to assess driving patterns that promote high emissions
      episodes, also known as emission excursions, particularly while driving on roads
      with grade. An instrumented vehicle was equipped to record driving conditions
      such as speed and grade, as well as measure emission rates of total hydrocarbons
      and carbon monoxide. Controlled runs with predetermined cruise speeds between 35
      and 55 mph and accelerations less than 3.3 mph/second were conducted on flat
      terrain and on hills with grades ranging from 0 to 7%. The hills were located in
      metropolitan Los Angeles, both along freeways and arterial roads. For
      hydrocarbons, the increase in emissions was about 0.04 g/mile for each 1% grade
      increment. For carbon monoxide (CO), the increase was more dramatic: 3.0 g/mile
      for each 1% grade increment. For a fully occupied vehicle with four passengers on
      a 4.5% grade, emissions increased by 0.07 g/mile for hydrocarbons and 10.2 g/mile
      for CO. Air conditioning operation, at full setting, further increased emissions
      while driving on hills (4.5 and 6.7% grades) by 0.07 g/mile for hydrocarbons and
      31.9 g/mile for CO.

PMID- 9269134
TI  - Airborne hexavalent chromium in southwestern Ontario.
AB  - This study reports the first field measurements of airborne hexavalent chromium
      (Cr(vi)) in southwestern Ontario. Hexavalent chromium was identified as an
      inhalation carcinogen and an air toxic of concern during the 1991-93 Windsor Air
      Quality Study. The results of that study indicated that approximately 20% of the
      routinely monitored ambient airborne chromium (Cr) was in the hexavalent form. In
      addition, the range of carcinogenic health risks attributable to airborne Cr(vi)
      was determined to be between 1.4 x 10(-5) and 3.0 x 10(-4) for people living in
      the Windsor area. During the summer of 1993, analyses of concurrent indoor and
      outdoor 24-hour air quality samples taken at 33 residences in Hamilton resulted
      in geometric mean Cr(vi) concentrations of 0.20 ng/m3 and 0.55 ng/m3,
      respectively, and little or no relationship between the indoor and outdoor sample
      sets. During the summer of 1994, an airborne Cr(vi) size-fraction study was
      conducted in Hamilton, the results of which suggested that the majority of the
      Cr(vi) was in the inhalable fraction.

PMID- 9269135
TI  - Predictive validity of the Braunwald classification of unstable angina for
      angiographic findings, short-term prognoses, and treatment selection.
AB  - The authors tested the Braunwald classification for its predictive validity for
      underlying coronary conditions, clinical courses, and responses to treatment. A
      reliable definition and classification of unstable angina is needed to help
      physicians make correct diagnoses of patients' conditions and to appraise
      findings from clinical trials critically. Many clinical trials have been
      conducted, but it is difficult to compare the results because of different entry
      criteria. Of 113 consecutive patients admitted with unstable angina, 89 who had
      primary angina were studied. Braunwald's classification was applied at admission.
      The outcomes of interest during hospitalization were coronary angiographic
      findings, short-term prognoses, and the treatment selected. Multivariate analysis
      showed that the severity class expressed significant positive predictivity for
      coronary thrombi (adjusted odds ratio [OR], 6.53; 95% confidence interval [CI],
      2.82 to 15.1) and progress to impending infarction (OR, 10.43; CI, 3.35 to
      32.49). The treatment (OR, 0.02; CI, 0.004 to 0.08) and electrocardiographic (OR,
      0.22; CI 0.10 to 0.49) classes showed independent negative predictivity for
      coronary vasospasm. The treatment (OR, 3.50; CI, 1.94 to 6.33) and
      electrocardiographic (odds ratio, 3.27; CI, 1.87 to 5.71) classes showed positive
      predictivity for the necessity for recanalization treatment with coronary
      angioplasty or bypass grafting. The Braunwald classification used at admission is
      highly predictive of underlying coronary conditions, progression to impending
      infarction, and the final selection of treatment. This classification should be
      considered in determining patient eligibility in clinical trials and studies.

PMID- 9269136
TI  - Posterior right diagonal artery. An angiographic study.
AB  - The purpose of this prospectively performed study was the angiographic
      visualization of the posterior right diagonal artery (PRDA) and its
      differentiation from the epicardial branches of the right coronary artery (RCA),
      that is, the right marginal artery and the posterior descending artery (PDA). The
      authors prospectively studied the angiographic findings of 607 patients who
      underwent coronary angiography. The incidence of the angiographically
      demonstrated PRDA and its distinction from other epicardial branches arising from
      the distal third of the RCA was the main point of interest. Two types of PDA in
      those cases where PRDA was present were also demonstrated. Of the patients
      examined, 535 had dominant right coronary circulation, 59 had left dominant
      coronary circulation, and 13 had balanced coronary circulation. PRDA was present
      in 81 patients with right dominant coronary circulation (15.1%), in 2 patients
      with balanced coronary circulation (15.4%), and in none with left dominant
      coronary circulation. PRDA was revealed in 48 (40%) of 120 patients with a short
      PDA and in only 33 (8%) of 415 patients having long PDA. It is imperative to
      search always for the PRDA, when one is studying coronary arteriographies,
      bearing in mind that this artery may perfuse the inferior part of the posterior
      interventricular septum and the adjoining are, depending on the type of PDA.

PMID- 9269137
TI  - An ovine model of acute myocardial infarction and chronic left ventricular
      dysfunction.
AB  - In order to develop and validate an ovine model of myocardial infarction with
      subsequent impairement of left ventricular function, 15 instrumented sheep
      underwent selective microembolization of the left coronary arteries with 0.5 mL
      90 microns polystyrene beads. Hemodynamics and plasma hormones were measured
      preembolization (baseline) and then at hours 2, 4, 6, and 12 and days 1, 2, 3, 5
      and 7 postembolization. Of the 15 sheep studied, 2 (13%) died on the day of
      embolization from arrhythmias. In the remaining sheep, left ventricular systolic
      pressure and stroke work (both P < 0.001) were reduced promptly and remained
      below basal levels. Mean arterial pressure (P < 0.001) increased initially, then
      decreased to below basal levels by hour 6. Heart rate (P < 0.001) and left atrial
      pressure (P < 0.05) were increased while cardiac output was decreased (P < 0.05).
      Left ventricular ejection fraction at day 7 was reduced (38.8 +/- 3.5 vs 46.0 +/-
      3.9% preembolization; P < 0.05). The cardiac enzymes creatine kinase (P < 0.001)
      and troponin-T (P < 0.001) were increased following microembolization and
      returned to basal levels by days 2 and 5 respectively. Plasma atrial and brain
      natriuretic peptides (both P < 0.001) and plasma renin activity (P < 0.005) were
      all increased following embolization. This ovine model mimics the hemodynamic and
      neurohumoral features of acute myocardial infarction, resulting in left
      ventricular dysfunction, and should prove suitable for the study of interventions
      in a number of these conditions.

PMID- 9269138
TI  - Effect of thromboxane A2 synthetase inhibitor on metabolism and contractility in
      ischemic reperfused rabbit heart.
AB  - The effect of thromboxane A2 synthetase inhibitor (OKY-046) on myocardial
      metabolism and contractility during ischemia and reperfusion was examined by the
      phosphorus 31-nuclear magnetic resonance (31P-NMR) in Langendorff rabbit hearts
      with use of an artificial blood substitute, perfluorochemical emulsion Fluosol
      43. After normothermic fifteen-minute global zero-flow ischemia or fifteen-minute
      global low-flow ischemia (coronary perfusion pressure = 20 mmHg), reperfusion of
      sixty minutes was carried out. OKY-046 was administered from forty-five minutes
      prior to the global ischemia. Adenosine triphosphate (ATP), creatine phosphate
      (CrP), inorganic phosphate (Pi), pH, left ventricular systolic developed pressure
      (LV Dev.P) and coronary flow were continuously measured. Twenty-eight heart were
      divided into four experimental groups consisting of 7 hearts each; Group I
      consisted of controls with zero-flow ischemia; Group II, perfusion with OKY-046
      (10(-6) M) in zero-flow ischemia; Group III, controls with low-flow ischemia; and
      Group IV, perfusion with OKY-046 in low-flow ischemia. Group II showed a
      significant inhibition of the increase in Pi and of the decrease in ATP, CrP, and
      pH during global ischemia compared with Group I, and a suppression of the
      overshoot of CrP observed after postischemic reperfusion. Group IV also showed a
      significantly marked improvement of ATP, CrP, and pH and significant suppression
      in Pi during low-flow ischemia compared with Group III. These were no differences
      in LV Dev.P and coronary flow among any groups. In conclusion, OKY-046 has a
      significantly beneficial effect on metabolism during both myocardial ischemia and
      reperfusion.

PMID- 9269139
TI  - Endovascular presence of Chlamydia pneumoniae in patients with hemodynamically
      effective carotid artery stenosis.
AB  - The bacterial pathogen Chlamydia pneumoniae has been associated with
      atherosclerosis. Recent studies have reported chlamydial antigen to be present in
      atherosclerotic coronary arteries, but this relation has not yet been widely
      accepted. In order to verify an endovascular presence of potentially viable
      chlamydiae by detection of genomic DNA, the authors examined atherosclerotic
      carotid arteries by using a C. pneumoniae-specific nested polymerase chain
      reaction. Chlamydial DNA was detected in 9 of 61 (15%) arterial samples obtained
      from therapy of hemodynamically effective cervical vascular stenosis. Chlamydial
      presence was limited to advanced atherosclerotic lesions (P < or = 0.02): tissues
      from the same arteries with early subendothelial lesions did not harbor the
      pathogen. Thus, an etiologic role of C. pneumoniae is more plausible for
      progression than for initiation of atherosclerotic lesions. Histomorphologic
      discrimination of infected and noninfected samples was not possible and serology
      was unrewarding in detecting the infected patients. Chlamydial occurrence in
      atheromatous plaques is apparently a general phenomenon of atherosclerosis not
      limited to coronary arteries. Endovascular presence of genomic DNA of a bacterial
      pathogen susceptible to antimicrobial agents encourages thought on a new approach
      to prevent progression of atherosclerosis in a substantial proportion of
      patients. However, an etiologic contribution of C. pneumoniae in the
      multifactorial process of atherogenesis yet remains to be demonstrated.

PMID- 9269140
TI  - Effect of enalapril maleate on cerebral blood flow in patients with chronic heart
      failure.
AB  - The effect of enalapril on cerebral blood flow (CBF) was studied in 11 patients
      with chronic heart failure (NYHA II or III, dilated cardiomyopathy in 6 and old
      myocardial infarction in 5). CBF was evaluated by analyzing the Patlak-Plot curve
      obtained from radionuclide angiography with technetium-99m hexamethylpropylene
      amine oxime (99mTC-HM-PAO). Cardiac index (CI) and stroke volume (SV) were
      simultaneously measured by impedance cardiography. These measurements were
      performed before and at four weeks after daily administration of 5 mg enalapril.
      The stroke volume, cardiac index, and heart rate were not significantly changed
      after four weeks of enalapril administration. However, CBF was increased by 6.5%
      from 36.72 +/- 4.66 to 39.13 +/- 5.65 mL/100g/min (P < 0.05). These results
      suggest that enalapril increased cerebral blood flow, which was not related to
      increased cardiac output in congestive heart failure. Patlak-Plot analysis of
      radionuclide angiography using 99mTC-HM-PAO may be available for quantitative
      assessment of brain perfusion.

PMID- 9269141
TI  - Fibrinogen and albuminuria are related to the presence and severity of peripheral
      arterial disease in women with type 2 diabetes mellitus.
AB  - The relationship between the ultrasonographically determined presence and
      severity of peripheral arterial disease (PAD) and cardiovascular risk factors was
      studied in 30 post-menopausal, nonsmoking women with type 2 diabetes mellitus.
      PAD was established on the basis of decreased ankle/arm index (AAI) of < 0.9 in
      15 patients. The control group included 15 type 2 diabetic women with AAI > 1.0.
      There were no differences with respect to diabetes control and systolic blood
      pressure between the patients with PAD and controls. The patients with PAD had
      significantly higher mean fibrinogen concentrations (4.75 +/- 0.35 vs 3.53 +/-
      0.36 g/L, P < 0.01) and urinary albumin excretion (UAE) values (893 +/- 501 vs 57
      +/- 24 mg/day, P < 0.05) than the subjects in the control group. There was no
      significant difference between the study groups with respect to any lipid
      variables. Significant partial correlations adjusted for age were observed
      between AAI (which expressed the severity of PAD) and log UAE (r = -0.55, P <
      0.01), creatinine (r = -0.48, P < 0.01) and fibrinogen (r = -0.45, P < 0.01). In
      the multiple stepwise regression analysis with AAI as a dependent variable, only
      fibrinogen (P = 0.033) and log UAE (P = 0.029) were included into the best model.
      In conclusion, in nonsmoking women with type 2 diabetes mellitus, fibrinogen and
      albuminuria were the only risk factors associated with both the presence and
      severity of peripheral arterial disease.

PMID- 9269142
TI  - Pulse oximetry in the evaluation of peripheral vascular disease.
AB  - The role of pulse oximetry in the evaluation of peripheral vascular disease (PVD)
      was investigated. In addition, the value of elevating the limb to improve the
      sensitivity of detection of PVD by the pulse oximeter was also determined. Pulse
      oximetry reading in the toes were obtained in 40 young, healthy volunteers and in
      40 randomly selected patients referred to the vascular investigation laboratory
      over a period of two months. All 40 healthy volunteers had normal pulse oximetry
      readings. Normal pulse oximetry reading in the toes was defined as > 95% O2 Sat
      and +/-2 of finger pulse oximetry reading. In all 40 patients, pulse oximetry
      readings were either normal or not detected at all. Since there was no gradation
      in decrease in the pulse oximetry reading with severity of disease or with
      elevation of the patient's lower extremity, an absent or no reading was
      considered as an abnormal result from the test. The frequency of abnormal pulse
      oximetry readings increased significantly in groups with abnormal ankle-brachial
      pressure index (ABPI) and also varied significantly with elevation of the
      patients' lower limbs. In patients with no PVD detected by Doppler (ABPI > 0.9),
      pulse oximetry readings were normal in all. However, in patients with moderate
      PVD (ABPI, 0.5-0.9), 84% of the patients' lower limbs had normal pulse oximetry
      readings and 16% had an abnormal reading at baseline level (flat). An additional
      12% of the lower limbs in this group had an abnormal reading on elevation of the
      limb to 12 inches. In patients with severe PVD (ABPI < 0.5), 54% of the patients'
      lower limbs had an abnormal reading at baseline and an additional 23% had an
      abnormal reading at elevation of the limb to 12 inches. In conclusion, pulse
      oximetry was not a sensitive test for detecting early PVD.

PMID- 9269143
TI  - Color Doppler echocardiographic evaluation of tricuspid regurgitation and
      systolic pulmonary artery pressure in the full-term and preterm newborn.
AB  - Color Doppler echocardiography of tricuspid valve regurgitation (TR) is a valid,
      noninvasive method of determining systolic pulmonary artery pressure (SPAP). In a
      prospective study the authors examined 56 healthy full-term newborns (group I),
      36 healthy preterm newborns (group II), and 10 preterm newborns with severe
      respiratory distress syndrome requiring surfactant replacement therapy (group
      III). Doppler studies were repeated until the transtricuspid gradient was < 20 mm
      Hg. In 83.3% of children a reproducible spectral curve was recorded at least
      once. The authors estimated the transtricuspid gradient delta p (RV-RA) by using
      the modified Bernoulli equation. Within the first twenty-four hours delta p (RV
      RA) was < 20 mm Hg in 72.7%, 50%, and 25% of children with measurable TR in
      groups I, II, and III, respectively, increasing to 91.1%, 78.6%, and 55.6% within
      forty-eight hours. There was no significant correlation between SPAP and
      gestational age, birth weight, mode of delivery, and ductal closing time.
      Continuous holosystolic envelope tracing of TR was recorded in 16.6%. In these
      patients delta p (RV-RA) was measured markedly higher (mean of 30.1 mm Hg) than
      in the others (mean 17.3 mm Hg). The authors conclude that there is a high
      prevalence of TR in neonates, which allows estimation of SPAP in > 80% of
      newborns without considerable impairment. Normalization of SPAP takes place
      within four days in most patients, but there is a delay in preterm infants with
      severe respiratory distress syndrome.

PMID- 9269144
TI  - New report of severe coronary artery disease in an eighteen-year-old girl with
      pseudoxanthoma elasticum. Case report and review of the literature.
AB  - An eighteen-year-old woman with pseudoxanthoma elasticum (PXE) suffered from mild
      angina pectoris over a ten-year period. Severe triple-vessel disease with mild
      left ventricular dysfunction was demonstrated on angiography. No
      revascularization was feasible. Despite a reported high frequency of angina
      pectoris among patients with PXE, only 10 convincing reports have appeared in the
      literature. Careful coronary artery evaluation is required in young patients with
      PXE, even though asymptomatic, because coronary artery disease (CAD) seems to be
      frequent and because no precise feature can be distinguished between types with
      or without severe vascular disease. Through very rare reports, surgical
      revascularization appears feasible and beneficial in a less severe form of CAD in
      patients with PXE. The risk of premature and severe diffuse CAD in PXE does not
      seem to be explained only by the combination of increased Lp [a] (or any other
      risk factor) and PXE.

PMID- 9269145
TI  - Excessive arterial thrombus in spherocytosis. A case report.
AB  - Spherocytosis is the most common of the hereditary hemolytic anemias, with
      characteristically shaped erythrocytes. An unusually large amount of arterial
      thrombus was documented in a dissected artery after angioplasty in a patient with
      spherocytosis. It is hypothesized that the excessive arterial thrombus may have
      been linked to the spherocytosis.

PMID- 9269146
TI  - Postoperative mitral valve abscess. A case report.
AB  - The authors report a case of a patient with postoperative perimitral
      bioprosthetic abscess and probable systemic embolization. The location of the
      abscess is not common and the use of porcine bioprostheses is supposedly
      associated with a low rate of embolic complications. Because of the high
      mortality and morbidity, it is stressed that patients with prosthetic valve
      endocarditis should be managed aggressively with surgery.

PMID- 9269147
TI  - Sprains of the knee. 1875.

PMID- 9269148
TI  - Hemiarthroplasty in the treatment of comminuted intraarticular fractures of the
      proximal humerus.
AB  - Thirty-eight patients with four-part proximal humerus fractures and fracture
      dislocations were treated with humeral head replacement between 1989 and 1995. At
      followup (mean, 37 months; range, 12-48 months) the patients were evaluated for
      postoperative pain, active range of motion, muscular strength, overall function
      in every day activities, and patient satisfaction. Complications developed in
      five patients and consisted of humeral component malposition (one shoulder),
      rotator cuff insufficiency (two shoulders), and heterotopic ossification (two
      shoulders). According to the Neer criteria, the overall results were: 32 (84%)
      patients had no pain and improved motion (active forward elevation averaged 130
      degrees, external rotation 45 degrees, and average internal rotation to the first
      lumbar vertebra); in this group strength and function 6 months postoperatively
      was 80% of the normal side and reached 90% of the normal side at 1 year
      postoperatively under continuous stretching and strengthening exercises; and 34
      patients (90%) were satisfied with their treatment. The results of the study
      indicate that humeral head replacement is a dependable method to restore comfort
      and function to patients with acute or old four-part fractures of the proximal
      humerus. However, recovery of function and range of motion are much less
      predictable in patients with an old injury.

PMID- 9269149
TI  - Elbow allograft for reconstruction of the elbow with massive bone loss. Long term
      results.
AB  - Transplantation of total elbow allografts has been used as a salvage procedure in
      an attempt to provide patients with functional, painless range of motion of the
      elbow. This procedure is appropriate for patients with massive bone loss after
      trauma, tumor resection, or revision elbow arthroplasty. During the past 20
      years, 23 patients have undergone elbow allograft reconstruction with variable
      results and a high complication rate. Ten of 14 patients with elbow allografts
      observed for an average of 7.5 years report satisfactory results. Allograft
      removal was required in six patients: for infection (two), instability (three),
      and nonunion and resorption (one). Three patients with instability have since
      undergone successful total elbow arthroplasty. Two patients have been observed
      less than 1 year and another patient died during the study period. Complications
      occurred in 16 of 23 patients. This operation is not recommended for routine use
      and is viewed as a salvage procedure. The use of allografts in elbow
      reconstruction does not preclude subsequent reconstruction with another allograft
      or fusion. In patients with deficient bone stock, the allograft reestablishes
      bone mass to permit an arthrodesis or reconstructive arthroplasty.

PMID- 9269150
TI  - Wrist arthrodesis. Technique and functional evaluation.
AB  - Wrist arthrodesis is a reliable procedure that, although it sacrifices motion for
      stability, provides the patient with relief from pain. This review of 26 wrist
      arthrodeses performed in 24 patients using the AO technique, with plate and screw
      fixation and iliac crest bone graft, shows a 100% union rate and high patient
      satisfaction. Using a questionnaire, the patients revealed that they adapted to
      their fused wrists but still had difficulty with some activities, such as getting
      the hand into tight places, heavy lifting, and positioning the hand for some
      specific activities. The most common complication was fracture at the ends of the
      plate. Removal of the plate after solid healing of the fusion is recommended
      strongly.

PMID- 9269151
TI  - Radiolunate fusion. The forgotten partial arthrodesis.
AB  - Radiolunate fusion has been used successfully in the treatment of rheumatoid
      ulnar translation of the carpus and degenerative radiolunate arthritis. Fusing
      the lunate to the radius places the keystone of the carpus in an aligned and
      stable position. The use of radiolunate fusion has been introduced here for other
      treatment challenges including traumatic ulnar translation of the carpus, dynamic
      midcarpal instability, volar and static intercalated segment instability. Pain
      relief was excellent and preoperative range of motion was maintained with
      radiolunate fusion.

PMID- 9269152
TI  - Outcome of distal radius fractures using the short form 36 health survey.
AB  - The Short Form 36, a survey designed to accurately study subjective findings, was
      applied to analyze the outcome of distal radius fractures and its' relation to
      extrinsic and intrinsic factors. The survey was administered to 50 adults (mean
      age, 49.6 years) requiring fixation of a distal radius fracture with a mean
      followup of 2.4 years. Treatment included external fixation and pins in 24
      patients, buttress plating in 20 patients, pins alone in four patients, and
      external fixation alone in two patients. The Short Form 36 scores were correlated
      with components possibly affecting outcome and compared with those of the general
      population. There was no correlation with residual radial height, radial tilt, or
      palmar tilt. No differences were observed between treatment or fracture groups.
      Intraarticular incongruence of 1 mm or greater correlated with a lower Short Form
      36 score and with the development of arthrosis. Those injured while working were
      more than four times less likely to return to work than those injured while away
      from work. The Short Form 36 was found an effective and precise tool for
      measuring subjective patient information.

PMID- 9269154
TI  - Charnley low friction arthroplasty in young patients with osteoarthritis. A 12-
      to 24-year clinical and radiographic followup study of 84 cases.
AB  - The long term outcome of 84 Charnley low friction arthroplasties performed
      between January 1973 and December 1984 on 69 patients (84 hips) with
      osteoarthritis was assessed. The patients were 55 years old or younger (mean, 46
      years) at the time of surgery. The probability of survival was 89.8% (range,
      85.9%-93.7%) after 10 years with 69 hips at risk and 73.3% (range, 65.5%-81.1%)
      after 18 years with 33.5 hips at risk. Of the 84 hips in the study, 24 (28.6%)
      failed. Of the hips that survived, clinical results were good and excellent with
      Charnley scores of four or more for pain and function in all hips. Of the hips
      that survived, 93.3% achieved good or excellent results for movement.

PMID- 9269153
TI  - Rationale of a flexible press fit cup in total hip replacement. 5-year followup
      in 280 procedures.
AB  - A consecutive series of 280 total hip replacements in 261 patients using the
      Press Fit Cup with a minimum followup of 5 years is presented. The Press Fit Cup
      is a nonmodular acetabular component with a porous coating made of titanium
      fibers. It has one peg and is 1.5 mm oversized with biradial eccentricity. It has
      a flattened pole area, requires no screw fixation, and partially preserves
      elasticity. The mean age was 71 years for women, 70 years for men. Forty-seven
      patients (49 hips) died before the 5-year review, and five patients were unable
      to return for the followup because of physical infirmity. Two hundred eighteen
      patients (226 hips) were available for the clinical 5-year followup, and 208
      patients (213 hips) were available for the radiographic followup. No
      intraoperative fracture of the acetabulum occurred; four hips dislocated; 94%
      clinically were rated as excellent or good. One hip in a patient with rheumatoid
      arthritis had to be revised for aseptic loosening of the cup and nine femoral
      stems had to be revised. No migration of the cup could be measured. There was no
      osteolysis seen around the cup. In six cases a radiolucent line was seen in Zone
      1, and in eight hips in Zone 3. There was one hip with a continuous radiolucent
      line which was considered radiographically loose.

PMID- 9269155
TI  - Total hip arthroplasty in neglected congenital dislocation of the hip.
AB  - Between 1984 and 1995, 74 total hip replacements were performed in 64 adult
      patients who had painful untreated congenital dislocation of the hip. The
      arthroplasty was performed in the position of the true acetabulum in all patients
      who had either high or low congenital dislocations of the hip. The femoral head
      was positioned in the true acetabulum after either osteotomy of the greater
      trochanter or shortening of the femur, or progressively using external fixation.
      Information was available on all patients with a followup of 1 to 11 years (mean,
      7.2 years). Of the 74 replaced hips, 70 showed marked improvement concerning
      pain, gait, and mobility, according to the Merle D'Aubigne and Postel scale. Four
      hips were revised with satisfactory results. The reason for revision was
      infection in one case and loosening of the plastic cup in three cases. Shortening
      of the femur by removing a segment of bone below the level of the lesser
      trochanter followed by osteosynthesis without osteotomy of the greater trochanter
      was found to be the best method for treating bilateral and several unilateral
      high congenital dislocation of the hip.

PMID- 9269156
TI  - Total hip arthroplasty for avascular necrosis and degenerative osteoarthritis of
      the hip.
AB  - Although several studies of various treatment modalities have been reported
      during the past decade, osteonecrosis of the femoral head remains a difficult
      therapeutic problem. Total hip replacement which is reserved for patients showing
      collapse of the femoral head, usually shows poorer results in patients with
      osteonecrosis compared with those with osteoarthritis. Uncemented total hip
      arthroplasty was performed on 29 patients with avascular necrosis of the femoral
      head and 29 patients with degenerative osteoarthritis. After a mean followup of
      7.6 years and 7.1 years for the two groups of patients, only one failure was
      observed in one patient with osteonecrosis. Clinical evaluation after cementless
      total hip arthroplasty in both groups of patients revealed improvement in all
      parameters. Postoperatively, pain improved from 1.4 to 5.1, walking ability from
      3.4 to 5.3, and range of motion from 4.5 to 5.5 in patients with osteonecrosis,
      and pain improved from 1.2 to 5.3, walking ability from 3.2 to 5.4, and range of
      motion from 3.1 to 4.7 in patients with osteoarthritis. Thigh pain was observed
      postoperatively in only two and three patients treated for osteonecrosis and
      osteoarthritis, respectively. The present results using cementless arthroplasty
      seem to be somewhat better than those reported for cemented arthroplasty in
      patients suffering from osteonecrosis. The clinical and radiographic findings
      after noncemented arthroplasty in patients with osteonecrosis of the femoral head
      and in patients with degenerative arthritis of the hip were similar in the two
      groups.

PMID- 9269157
TI  - Anterior cruciate ligament reconstruction. Bone-patella tendon-bone versus
      semitendinosus anatomic reconstruction.
AB  - In this article, the long term (2-10 years; mean, 4.8 years) followup results of
      two reconstructive procedures for the anterior cruciate ligament are compared.
      The bone-patella tendon-bone (with interference fit fixation) was performed on 69
      knees, and the semitendinosus anatomic reconstruction was performed on 68 knees,
      in a population of 76 men and 52 women (age range, 15-60 years; average, 31
      years). The patients in the two groups showed no difference in subjective results
      or activity level and no significant difference to manual testing. The
      semitendinosus procedure group had a slightly higher KT manual maximum failure
      rate than the patella tendon group (17% versus 11%). Arthrometric stability did
      not show deterioration, but patient satisfaction decreased in those patients who
      had meniscectomies. Both procedures showed satisfactory results during the long
      term followup. However, if the secondary restraints are compromised, the stiffer
      bone-patella tendon-bone construct is preferred for reconstruction of the chronic
      anterior cruciate ligament deficient knee.

PMID- 9269158
TI  - Infected total knee arthroplasty. Two-stage reimplantation with a gastrocnemius
      rotational flap.
AB  - This study reviews a consecutive series of 21 patients undergoing two-stage
      reimplantation total knee arthroplasty for late chronic infection. All 21
      patients had late chronic infections, and 20 of 21 patients were compromised
      hosts. Seven different organisms were isolated at the time of prosthetic
      resection. Staphylococcus coagulase negative species was the most frequently
      isolated organism. At the time of reimplantation, a medial gastrocnemius
      rotational flap was rotated over the proximal tibia and knee for wound closure.
      The average explantation time was 25 weeks (range, 7-76 weeks), and no
      methylmethacrylate spacers were used. At an average 17-month followup (range, 5.1
      33.1 months) all reimplanted total knee replacements remained in place with one
      patient having recurrent infection. At reimplantation, 11 patients had positive
      bacterial cultures from tissue specimens. Sixteen of the 33 (40%) positive
      cultures were from specimens taken from the medullary canal. At followup, the
      average Knee Society Score was 77.4 (range, 40-100). The lack of a
      methylmethacrylate spacer and a long explantation time were considered important
      factors in diminishing functional performance and determining the need for a
      gastrocnemius flap. A medial gastrocnemius rotational flap should be considered
      at the time of reimplantation total knee arthroplasty if the soft tissue envelope
      about the knee is compromised and cannot be closed without undue tension.

PMID- 9269159
TI  - Idiopathic osteonecrosis of the medial femoral condyle. Classification and
      treatment.
AB  - Idiopathic osteonecrosis of the medial femoral condyle is a well recognized cause
      of spontaneous, sudden onset of severe pain, usually at the anteromedial aspect
      of the knee joint. At the Department of Orthopaedic Surgery of the University of
      Ioannina, 105 knees in 101 patients were evaluated and treated for idiopathic
      osteonecrosis of the medial femoral condyle. The disease was found to follow a
      four-stage course, which consisted of a progression from no radiographic findings
      (Stage I), to a slight flattening of the medial condyle (Stage II), followed by
      the appearance of a radiolucent lesion (Stage III), and finally, articular
      cartilage collapse (Stage IV). Although Stages I and II potentially were
      reversible, Stages III and IV were associated with irreversible destruction of
      the subchondral bone and articular cartilage. Although bone scan is a nonspecific
      diagnostic modality, it was helpful in establishing diagnosis in the early stages
      of the disease. Conservative treatment was found appropriate for the first two
      stages, whereas surgical management was effective for patients with Stages III
      and IV. Specifically, osteotomy was useful for patients younger than 60 years of
      age with limited necrotic lesions, whereas unicompartmental arthroplasty was
      effective in older patients with more extensive lesions. Total knee arthroplasty
      can be reserved for cases where the disease has expanded to the lateral
      compartment.

PMID- 9269160
TI  - Surgical treatment of malleolar fractures. A review of 144 patients.
AB  - Malleolar fractures are one of the most common fractures faced in orthopaedic
      surgery. The results from a consecutive series of 144 malleolar fractures during
      a 10-year period that were classified and treated according to the AO system are
      presented. Assessment of outcome was done using the scoring system of Baird and
      Jackson, which is based on subjective, objective, and radiographic criteria.
      Excellent and good results were achieved in 107 of the 144 patients surgically
      treated. Overall, excellent and good results were obtained in almost all
      unimalleolar fractures, but were significantly less in bimalleolar fractures.
      There was no difference in outcome achieved between Weber C and Weber D
      fractures. The presence of a large bony fragment or dislocation also
      significantly affected the final outcome. Posttraumatic osteoarthritis was found
      to be associated significantly with poor clinical results, bimalleolar fractures,
      and unsatisfactory surgical reduction.

PMID- 9269161
TI  - Results of surgical treatment of tibial plafond fractures.
AB  - To clarify which factors influence the final result of surgical management of
      plafond or pilon fractures, 66 patients with 67 pilon fractures treated at the
      Orthopaedic Department of the University of Athens between 1978 and 1993 were
      reviewed. There were eight (11.95%) Type I, 33 (49.25%) Type II, and 26 (38.8%)
      Type III fractures according to the Ruedi-Allgower classification. Eleven (16.4%)
      were open injuries. Fifty of the 67 fractures were treated by internal fixation
      following the AO principles, whereas minimal osteosynthesis was performed in nine
      cases, and the remaining eight cases were managed by external fixation. The final
      outcome of the treatment was evaluated after 2 to 17 years followup (mean, 8.1
      years) and was based on the subjective, objective, and radiographic results of
      each case, using the method of Burwell and Charnley. The findings indicate that
      three parameters significantly influenced the outcome of plafond fracture
      management. Specifically, the results of surgical management were affected by the
      clinical type of the fracture, the quality of reduction achieved at surgery, and
      the specific surgical procedure by which the fracture was managed.

PMID- 9269162
TI  - Treatment of acquired adult planovalgus deformities with subtalar fusion.
AB  - A retrospective review was conducted of isolated subtalar arthrodeses performed
      on 32 adults (34 fusions) between August 1990 and September 1993. Each fusion was
      performed using a single large cannulated lag screw through the talar neck. The
      American Orthopaedic Foot and Ankle Society standard clinical rating system for
      the ankle and hindfoot was used to assess outcome. Patients answered subjective
      questions based on the scale. Followup examination was done to evaluate
      clinically and radiographically each patient's foot and ankle according to the
      scale. Average patient age was 53 years (range, 27-80 years). Average followup
      was 30.8 months (range, 16-55 months). Twenty-four patients answered the
      subjective questions, and the average subjective score was 47 of a maximum 60
      points (range, 9-60 points). Clinical data from 17 patients showed an average
      objective score of 30 of a maximum 34 points (range, 25-34 points). The average
      total score was 77 of a maximum 94 possible points (range, 34-94 points). Forty
      two percent of the patients indicated a 100% improvement, 42% a 75% improvement,
      and 16% a 50% improvement. Eighty-three percent stated they definitely would have
      the procedure again. Results indicate that subtalar arthrodesis is an effective
      treatment for adult patients with pain and disability secondary to acquired
      planovalgus, posttraumatic, and inflammatory conditions of the hindfoot. In
      addition, the American Orthopaedic Foot and Ankle Society standard rating system
      of the ankle and hindfoot corresponds to clinical outcome.

PMID- 9269163
TI  - Percutaneous repair of Achilles tendon rupture. Immobilization versus functional
      postoperative treatment.
AB  - Between 1987 and 1992, 48 patients with ruptured Achilles tendons were operated
      on using a standardized microinvasive technique; 30 patients underwent functional
      postoperative treatment, whereas 18 underwent conventional cast immobilization.
      Validated tests and a specially designed instrument for measuring strength and
      endurance were used for followup examinations. Patients undergoing functional
      postoperative treatment were hospitalized for shorter periods and lost fewer days
      from work than those in the cast group. Tests of ankle mobility showed more
      pronounced limitations of plantar flexion in cast immobilized versus functionally
      treated patients. Patients in the cast group also did less well on maximal one
      leg tiptoeing. Percutaneous Achilles tendon repair with functional postoperative
      treatment and early full weightbearing was associated with significantly less
      severe limitations of calf muscle work by the injured leg than postoperative cast
      immobilization. The rerupture rate was no higher than after cast immobilization,
      but lower than after open surgical repair or conservative functional treatment
      alone. Unlike those undergoing conservative functional treatment, patients need
      not wear special boots at night or be observed by ultrasound studies at regular
      intervals. Because the procedure can be done on an outpatient basis and because
      patients lose significantly fewer days from work than those immobilized in a
      cast, cast immobilization after Achilles tendon suture repair is no longer
      justified.

PMID- 9269164
TI  - Reconstruction of residual deformities of the hip. A new surgical option.
AB  - Shortening of the femoral neck and relative overgrowth of the greater trochanter
      are the main problems after avascular necrosis of the capital femoral epiphysis.
      A new type of femoral osteotomy was performed in 16 patients to lengthen the
      femoral neck, improve the biomechanics of the hip joint with a better congruity
      of the head, and to restore the leg length discrepancy. Clinical and radiologic
      followup showed good results in all the patients after a mean time of 4.3 years.
      Relief of pain, a negative Trendelenburg sign, and improvement of hip movements,
      particularly abduction, were the most significant short term results.

PMID- 9269165
TI  - Decline of bone and joint infections attributable to haemophilus influenzae type
      b.
AB  - Haemophilus influenzae has been a major cause of infectious diseases in children
      and has been attributed as a significant cause of septic arthritis and
      osteomyelitis in children. With the advent of widespread vaccination, the
      incidence of Haemophilus influenzae meningitis and other infections has been well
      documented. This is thought to be the first report that documents the effect of
      vaccination on bone and joint infections. One hundred sixty-five cases of acute
      hematogenous osteomyelitis or septic arthritis treated at the Department of
      Orthopaedics at Vanderbilt University in the years before and after the advent of
      the Haemophilus influenzae vaccine to assess whether vaccination affected the
      incidence of these diseases. The data indicate that the Haemophilus influenzae
      vaccine has reduced to near 0 the incidence of bone and joint infections because
      of Haemophilus influenzae. These findings suggest that coverage of Haemophilus
      influenzae as part of the empiric antibiotic coverage may be no longer needed in
      the management of acute hematogenous osteomyelitis and septic arthritis in
      children.

PMID- 9269166
TI  - Split pectoralis major transfer for serratus anterior palsy.
AB  - The results of split pectoralis major tendon transfer (sternal head) for
      symptomatic scapular winging because of palsy of the serratus anterior muscle
      were reviewed. Eleven consecutive patients, whose average age was 34 years, had a
      duration of preoperative symptoms ranging from 12 to 60 months. Ten patients had
      electromyograms documenting a long thoracic nerve injury. Using an inferior
      axillary incision, the tendon of the sternal head of the pectoralis major is
      mobilized and transferred to the inferior angle of the scapula. The tendon
      transfer is reinforced with autogenous fascia lata. After surgery, a
      scapulothoracic orthosis is worn for 6 weeks, and restriction of vigorous
      activities is recommended for 6 months. At an average followup of 41 months, 10
      of 11 (91%) patients had satisfactory results with significant improvement in
      function and reduction of pain. Each of these 10 patients had improved scapular
      tracking with no scapular winging or mild, dynamic winging at latest followup.
      One patient had an unsatisfactory result with a full recurrence of scapular
      winging secondary to noncompliance with the postoperative physical therapy
      regimen. The split pectoralis major tendon transfer provides a reasonable
      substitute for a paralyzed serratus anterior muscle in scapular stabilization.
      Strict adherence to technical principles and postoperative rehabilitation
      reliably leads to satisfactory clinical results.

PMID- 9269167
TI  - Microscopic studies of human press fit titanium hip prostheses.
AB  - Seven cementless, press fit, rectangular cross section, titanium alloy femoral
      prostheses were implanted for the treatment of displaced subcapital hip fractures
      in elderly patients and retrieved postmortem for microscopic evaluation. The mean
      patient age was 88 years (range, 66-103 years), and prostheses were in situ an
      average of 29 months (range, 6-45 months). Microscopic examination of the
      specimens revealed regions of bone to prosthesis contact without interposed
      connective tissue, and all were considered stably osseointegrated. The mean
      microscopic bone to prosthesis contact for five cross sections was 28%.
      Implantation of this prosthesis achieved satisfactory primary stability in
      endosteal cortical bone in these elderly patients. Secondary stabilization was
      apparent, as evidenced by new, viable bone formation and remodeling in apposition
      to the prosthesis.

PMID- 9269168
TI  - Posterior instability of the hip in an adult. A case report.
AB  - Dislocation of the hip except as a congenital or developmental lesion is not
      common, and the onset of symptoms because of posterior instability of the hip in
      an adult has not been reported previously. An adult patient who had benign
      congenital hypotonia as an infant and who presented with generalized ligamentous
      laxity and hip pain associated with recurring posterior subluxation of the hip is
      the subject of this report.

PMID- 9269169
TI  - High tibial osteotomy in the treatment of adult osteochondritis dissecans.
AB  - This study reports one surgeon's experience using valgus high tibial osteotomy in
      the treatment of osteochondritis dissecans of the medial femoral condyle in adult
      patients. Seven knees in six patients with osteochondritis dissecans were
      reviewed as the basis of the study. Five patients (five knees) were men, and one
      patient (two knees) was a woman. The average age at surgery was 32 years.
      Patients reported medial knee pain, recurrent effusions, and disability. An
      average of three procedures per knee had been performed previously. Four knees
      had achieved union of the osteochondral fragments but with overlying articular
      cartilage degeneration observed at arthroscopy. Three knees had failed attempts
      at fixation with eventual excision of the fragmented osteochondral lesions. None
      of the knees showed diffuse medial compartment gonarthrosis by radiographic or
      arthroscopic examinations. Involved knees had relative varus malalignment with an
      average femoral and tibial angle of 0 degree compared with the uninvolved knees
      average of 5 degrees valgus. Preoperative technetium scintigraphy showed isolated
      uptake in the medial femoral condyle of all involved knees. Preoperative Lysholm
      scores averaged 39 points. Patients were observed for an average of 30 months
      after surgery. The average Lysholm score at latest followup was 89 points.
      Femoral and tibial angles averaged 9 degrees valgus. On subjective questioning,
      all patients reported marked improvement, satisfaction with the surgery, and said
      they had no need for additional operative intervention.

PMID- 9269170
TI  - Abnormal skeletal growth in Kniest dysplasia caused by type II collagen
      mutations.
AB  - Two unrelated patients with Kniest dysplasia had the same substitution of a CG
      dinucleotide in exon 12 of the COL2A1 gene that resulted in alternative splicing
      and interruption of the triple helix of a1(II) chains of Type II collagen. In
      early childhood, they shared the typical clinical and radiographic features of
      Kniest dysplasia. However, one child was affected more severely from birth and
      showed progressive severe disruption of growth plates with retarded longitudinal
      growth, deformities from asymmetric growth, and widespread sclerosis of the
      epiphyses. Both children had clinical and radiographic signs of degenerative
      arthritis of many joints by 11 years of age. The phenotypes in these children
      highlight the importance of exon 12 mutations of COL2A1 in the pathogenesis of
      Kniest dysplasia.

PMID- 9269171
TI  - Subtrochanteric femoral fractures in children. Alignment after 90 degrees-90
      degrees traction and cast application.
AB  - Fifteen children younger than 10 years of age with subtrochanteric fractures
      treated by a uniform method were evaluated. These patients had been treated with
      femoral skeletal traction, with the hip and knee flexed to 90 degrees until
      radiographic callus appeared, then with a hip spica cast. True neck to shaft and
      anteversion angles were calculated bilaterally using a biplanar method. Leg
      lengths were measured radiographically and clinically. Mean age at injury was 4.5
      years, and mean followup was 6.5 years. Overgrowth averaged 10 mm after fracture.
      Anteversion at final followup differed only by a mean of 2 degrees from the
      contralateral side (range, -3 degrees to +4 degrees), and the mean neck shaft
      angle differed by only 1 degree. Remodeling of coronal angulation was 50% or more
      in all cases.

PMID- 9269172
TI  - Intertrochanteric osteotomy for failed internal fixation of femoral neck
      fracture.
AB  - Thirteen patients with failed internal fixation of the femoral neck were treated
      with valgus intertrochanteric osteotomy performed by one surgeon from 1987 to
      1995. The patients ranged in age from 18 to 59 years. The interval from injury to
      osteotomy ranged from 4 to 54 weeks. With an average followup of 25 months
      (range, 9-42 months), the femoral neck fracture healed in all patients. Twelve
      patients returned to being fully weightbearing without pain. The average limb
      shortening was improved by 1 cm. Seven of eight patients who were employed before
      their injuries returned to the same occupations. Femoral head collapse because of
      avascular necrosis developed in one patient 18 months after surgery and return to
      full activities and in a second patient shortly after the osteotomy. These two
      patients now have an arthroplasty. The remainder of the patients have done well
      without requiring additional surgery. Harris hip scores and Short Form 36 Health
      Status Survey outcome scoring were available to verify the results in 10
      patients.

PMID- 9269173
TI  - Management of complex dislocations of the distal radioulnar joint.
AB  - The authors reviewed their experience in the treatment of complex dislocations of
      the distal radioulnar joint. Six cases of complex dislocations were treated
      between 1990 and 1993. An algorithm for the treatment of these injuries has been
      developed. In most cases, complex dislocations are associated with an avulsion
      fracture of the ulnar styloid. The authors prefer to treat these by fixation of
      the ulnar styloid using a tension band wiring technique. Cases in which the ulnar
      styloid fragment is small, or in which there is no styloid fracture, are treated
      with open reduction and repair of the triangular fibrocartilage complex if the
      distal radioulnar joint is irreducible, or by ulnoradial transfixion pinning if
      the distal radioulnar joint is reducible but unstable. Good results were obtained
      in five of six cases using this algorithm.

PMID- 9269174
TI  - Prosthetic hip replacement for pathologic or impending pathologic fractures in
      myeloma.
AB  - The authors retrospectively reviewed 53 hip replacements performed in 50 patients
      (mean age, 65 years) for plasmacytoma (four lesions) or multiple myeloma (49
      lesions) of the hip region. Perioperatively, 49 patients received chemotherapy.
      Twenty-four hip lesions had radiation therapy. Within a mean followup period of
      32.6 months, 15 (28%) complications occurred. Late deep infection, dislocation,
      and aseptic loosening with medial migration of the acetabular component occurred
      in one patient each. Three patients died during the first postoperatively month.
      All of the remaining patients postoperatively regained their previous ambulatory
      status; hip pain relief was achieved in 98% of patients. At the time of the
      latest followup evaluation, 84% of the patients had died (median survival time,
      18 months) and 16% were still alive (median survival time, 76 months). Patients
      with plasmacytoma had longer survival than did patients with multiple myeloma
      (median survival, 6.3 years versus 18 months, respectively). No significant
      association was found between patient survival and the stage of disease at
      diagnosis, age, gender, type or location of the myeloma lesion, or the type of
      implant used. Because of the relatively long survival time, prosthetic
      replacement is indicated for extensive hip lesions in patients with plasmacytoma
      or multiple myeloma.

PMID- 9269175
TI  - Treatment of osteomyelitis with a biodegradable antibiotic implant.
AB  - A biodegradable antibiotic implant was developed and evaluated in a localized
      osteomyelitic rabbit model. The biodegradable antibiotic implant was made of
      polylactic acid and poly(DL-lactide):co-glycolide combined with vancomycin.
      Localized rabbit tibial osteomyelitis was developed with Staphylococcus aureus.
      Infected rabbits were divided into eight groups, depending on treatment with or
      without debridement, systemic antibiotics, or biodegradable beads. After 4 weeks
      of therapy, the radiographs were obtained of the involved bones, which also were
      cultured for concentrations of Staphylococcus aureus per gram of bone. Treatment
      with antibiotic containing polylactic acid and poly(DL-lactide):co-glycolide
      beads, with and without systemic vancomycin, resulted in bone colony forming unit
      levels of 10(2.93) and 10(2.84) colony forming units per gram bone, respectively.
      These bacterial concentrations were approximately 100 times lower than those
      observed for all other treatment groups. A biodegradable antibiotic bead may
      provide extended bactericidal concentrations of antibiotics for the time needed
      to completely treat the particular orthopaedic infection and does not require the
      surgery needed to remove the polymethylmethacrylate beads.

PMID- 9269176
TI  - Postosteotomy healing in Pyle's disease (familial metaphyseal dysplasia). A case
      report.
AB  - Pyle's disease is rare skeletal dysplasia in which a defect in metaphyseal
      remodeling leads to grossly widened metaphyses of long bones. Genu valgum, one of
      the few clinical findings in this disease, may warrant surgical intervention.
      Postoperative healing is documented only in Pyle's original patient. A case is
      presented in which bilateral osteotomies were performed through the proximal
      tibia for progressive genu valgum. The osteotomies healed within 12 weeks when
      treatment was performed with standard techniques. This information will allow
      osteotomies to be performed with confidence.

PMID- 9269177
TI  - Prevention of deformity during limb lengthening.
AB  - Deformity occurs frequently at the site of distraction during leg lengthening and
      can add to disability. The elastic and nonelastic displacements have been
      measured in a model that simulates leg lengthening in the laboratory.
      Measurements have been made for different fixator systems. The angulation in the
      vertical plane that occurs during leg lengthening is minimized if the distance
      between the bone and the fixator bar is kept as small as possible, if three
      screws are inserted in the proximal and distal bone fragments, and if the peak
      loads on the fixator are reduced by adjusting the rhythm of distraction. However,
      even if these precautions are taken, the results show that some fixators designed
      for leg lengthening will fail and lead to deformity at the osteotomy site. This
      may occur under the repeated cycles of high loads associated with the rises in
      soft tissue tension that are known to occur in certain groups of patients. This
      study suggests that deformity can be prevented by the proper selection of a
      suitable frame and the adjustment of its configuration to meet the loading
      requirements.

PMID- 9269178
TI  - Contribution of the anterolateral joint capsule to the mechanical stability of
      the ankle.
AB  - Published reports describe the clinical efficacy of modified Brostrom anatomic
      repairs, surgical procedures that involve repair and fortification of the lateral
      capsuloligamentous complex of the ankle for patients suffering from chronic
      lateral instability of this joint. A cadaveric serial sectioning study of the
      anterior talofibular ligament, the calcaneofibular ligament, and the remainder of
      the anterolateral joint capsule was completed to quantitate the contribution of
      the superior portion of the anterolateral joint capsule, independent of the other
      two structures, to the overall mechanical stability of the lateral ankle. Using
      20 fresh frozen specimens, talar tilt and anterior drawer stress radiographs were
      taken before and after sectioning these anatomic structures in an order
      established by one of two protocols. Sectioning of the superior anterolateral
      joint capsule caused 17% to 18% of the total displacement in a Grade II sprain
      simulation and 29% to 33% of the total displacement in a Grade III sprain
      simulation. This work suggests that disruption of the segment of ankle joint
      capsule superior to the anterior talofibular ligament creates approximately 30%
      of the overall laxity encountered in a Grade III inversion sprain, substantiating
      the principle of restoring the integrity of the entire anterolateral joint
      capsule when operating on a chronically unstable ankle.

PMID- 9269179
TI  - Stability of proximal femoral grafts in canine hip arthroplasty.
AB  - In a canine model, the fixation stability of a prosthesis and proximal bone graft
      composite were measured relative to the distal femur. One group had the
      prosthesis graft composite cemented into the distal femur. The second group had
      the prosthesis graft composite press fit into the distal femur for biologic
      ingrowth. Displacements of the proximal femoral grafts relative to the host bone
      in each group were measured after ex vivo (acute with graft) implantation and 4
      months after implantation. A third group with no osteotomy (acute intact)
      simulated perfect graft to host bone union. Relative displacements representing 6
      degrees freedom (translation and rotation) were calculated from the displacement
      values measured by 9 eddy current transducers. Measurements of displacement were
      used to test the hypothesis that distal press fit fixation equals distal cement
      fixation at 4 months after implantation. In all cases the measured translations
      and rotations of the graft to implant construct were small and of a magnitude
      that should encourage bone ingrowth (< 0.05 mm and < 0.1 degree, respectively).
      The stability of the press fit group at 4 months was not significantly different
      from the cemented group in axial and transverse displacement during axial and
      transverse loading, respectively. There was no difference in stabilities at 4
      months between distal press fit and cemented fixation in hip replacements
      requiring a proximal femoral graft.

PMID- 9269180
TI  - Pullout strengths of cannulated and noncannulated cancellous bone screws.
AB  - The pullout strengths of large diameter cannulated and noncannulated cancellous
      screws were tested in a synthetic polyurethane foam. The foam was fabricated to
      have mechanical properties equivalent to human cancellous bone and was
      characterized by compression testing before screw pullout. Long and short thread
      commercially available screws from four manufacturers were tested. In screws with
      short threads (16-22 mm), there was no difference in holding power among the four
      cannulated screw designs. However, the short thread noncannulated screw performed
      significantly better than the short thread cannulated screw with the lowest
      pullout strength. There were statistically significant differences in holding
      power among the different long thread (32-40 mm) cannulated screw designs.
      Additionally, the long thread noncannulated screw had better holding power than
      several of the long thread cannulated screws. No differences in pullout strengths
      between comparably sized cannulated and noncannulated screws produced by the same
      manufacturer were found, and all long thread screws had significantly greater
      holding power than all short thread screws. There was no demonstrable effect on
      holding power when screws were inserted with or without tapping. Thread surface
      area was found to be a reasonable predictor of holding power.

PMID- 9269182
TI  - Knee kinematics of posterior cruciate ligament sacrificed total knee
      arthroplasty.
AB  - Two different posterior stabilizing mechanisms in posterior cruciate ligament
      sacrificing total knee arthroplasty were evaluated to test knee kinematics,
      tibiofemoral contact location, and the quadriceps force needed to extend the
      knee. A posterior stabilizing post and a deeply dished polyethylene with a high
      anterior lip (anterior buildup stabilizing tibial articular surface) were tested
      in four anatomic specimen knees with a knee kinematics testing device. Both
      posterior stabilizing mechanisms partially restored anteroposterior stability,
      but the knees were still more lax than were the normal knees in the
      anteroposterior direction. The anterior buildup stabilizing tibial articular
      surface decreased rotational laxity in early flexion. Tibiofemoral contact
      location in the knees with the anterior buildup stabilizing tibial articular
      surface did not move posteriorly as the knee flexed, and the knees with this
      articular surface required significantly more quadriceps force to extend the knee
      than did the knees with a stabilizing post.

PMID- 9269181
TI  - Analysis of longitudinal arch supports in stabilizing the arch of the foot.
AB  - Two orthotic devices commonly prescribed as arch supports were studied to
      evaluate their efficacy in stabilizing the foot. Fourteen cadaveric feet were
      mounted in a loading frame, and an axial load of 222, 445, or 667 N was applied
      while three-dimensional positions of the talus, calcaneus, navicular, and first
      metatarsal were monitored with a magnetic tracking system. Feet were tested with
      and without the use of two commonly prescribed arch supports. The two indices
      used to assess arch stabilization were arch height and joint rotation. Joint
      rotations consistently increased on load application. Significant differences
      were observed with Inserts 1 and 2 in metatarsal talar abduction, dorsiflexion
      and eversion, calcaneal talar eversion, and talar tibial dorsiflexion. Arch
      height significantly increased with both inserts. Contrary to previously
      published results, the arch supports that were studied provided measurable
      improvement in arch stability in a simulated standing at ease position.

PMID- 9269183
TI  - The Nicolas Andry Award-1995. Fracture healing. Radiation induced alterations.
AB  - This study investigated the effects of radiation on fractures in a rat femur
      model. Two different radiation dosage fractionation schemes (1100 rads given in
      one dose and 2500 rads given in 10 divided doses over 12 days) and three
      different times of initiation of radiation (1 day before fracture, 3 or 10 days
      after fracture) were studied. Fractures exposed to these levels of radiation all
      appeared to heal during the course of this experiment, although with varying
      degrees of delay, with the exception of those exposed to a single dose of 1100
      rads 3 days after fracture. These animals remained at a more immature level of
      repair histologically compared with the control group, throughout the entire time
      evaluated. The strength of the final repair remained less than the control for
      all the groups receiving treatment. These results may offer some explanation for
      the clinical observations of an increased incidence of delayed union and nonunion
      of fractures, an increased incidence of fracture and refracture in irradiated
      bone, and an increased incidence of fracture and nonunion in constructs using
      radiation in conjunction with allogeneic bone. Furthermore, the observed effects
      were generally no different in the animals treated with the two clinically
      relevant dose fractionation schemes chosen for this study.

PMID- 9269184
TI  - Shoulder pain in a 15-year-old boy.

PMID- 9269185
TI  - A normal congruence (Q angle)

PMID- 9269187
TI  - "For any shortcomings on the part of the Red Cross, we are deeply sorry".

PMID- 9269188
TI  - "For any shortcomings on the part of the Red Cross, we are deeply sorry".

PMID- 9269189
TI  - "For any shortcomings on the part of the Red Cross, we are deeply sorry".

PMID- 9269190
TI  - NBSS: opportunity to compromise the process.

PMID- 9269191
TI  - NBSS: changes were made, suspicious changes were not.

PMID- 9269192
TI  - Thrombolytic therapy: time to treatment.

PMID- 9269193
TI  - Facing breast cancer far from radiation therapy centres.

PMID- 9269194
TI  - Worried residents watch and wait.

PMID- 9269195
TI  - Needle exchange programs: an economic evaluation of a local experience.
AB  - OBJECTIVE: To determine whether providing a needle exchange program to prevent
      HIV transmission among injection drug users would cost less than the health care
      consequences of not having such a program. DESIGN: Incidence outcome model to
      estimate the number of cases of HIV infection that this program would prevent
      over 5 years, assuming that the HIV incidence rate would be 2% with the program
      and 4% without it, and that an estimated 275 injection drug users would use the
      service over this time. SETTING: Hamilton, Ont. OUTCOME MEASURES: Estimated
      number of cases of HIV infection expected to be prevented with and without the
      program over 5 years; estimated lifetime health care costs of treating an AIDS
      patient. The indirect costs of AIDS to society (e.g., lost productivity and
      informal caregiving) were not included. Projected costs were adjusted
      (discounted) to reflect their present value. In a sensitivity analysis, 3
      parameters were varied: the estimate of the HIV transmission rate if no needle
      exchange program were provided, the number of injection drug users participating
      in the program, and the discount rate. RESULTS: With very conservative estimates,
      it was predicted that the Hamilton needle exchange program will prevent 24 cases
      of HIV infection over 5 years, thereby providing cost savings of $1.3 million
      after the program costs are taken into account. This translates into a ratio of
      cost savings to costs of 4:1. The sensitivity analysis confirmed that these
      findings are robust. CONCLUSION: Needle exchange programs are an efficient use of
      financial resources.

PMID- 9269196
TI  - Regional variation in nonmedical factors affecting family physicians' decisions
      about referral for consultation.
AB  - OBJECTIVE: To determine whether there is regional variation in environmental (non
      medical) factors affecting referral decisions of family physicians (FPs). DESIGN:
      Cross-sectional interview survey. SETTING: Nova Scotia. PARTICIPANTS: A random
      sample of 125 FPs grouped into 1 of 5 functionally defined geographic regions of
      Nova Scotia (25 in each group). Groupings were based on access to general
      hospital beds through active staff hospital appointments or to specialist
      consultants in the community, or both. Participants were personally interviewed
      on site. No physician refused an interview. In 9 cases the physician indicated
      that he or she did not fit the profile of the assigned group; the physician was
      excluded from the study and the next doctor on the list was substituted. OUTCOME
      MEASURES: The questionnaire was designed to test several hypotheses about factors
      known to potentially influence decisions about referral. Geographic differences
      in factors affecting referral and in decisions about 5 hypothetical cases were
      assessed with the use of significance tests for proportions that were sensitive
      to specific orders across groups. RESULTS: Three factors affecting referral
      showed unequivocal variation across the 5 groups. Access to hospital facilities
      and remoteness from specialist care, leading to local styles of practice or
      treatment policies, and the FP's relationship with specialist consultants
      appeared to be important nonmedical factors affecting referral decisions. For
      similar case scenarios the physicians living in rural areas would refer only half
      as often overall as those living in urban areas with tertiary care hospitals; for
      some cases, such as a severe asthma attack, the difference was more than 7-fold.
      CONCLUSIONS: Significant differences in nonmedical factors affecting referral,
      and in referral decisions about hypothetical cases, were found between the groups
      of FPs. Differences in access to resources, creating local styles of practice,
      appeared to explain most of the variation. The results may account for previously
      observed differences in actual rates of referral for these particular groups.

PMID- 9269197
TI  - Needle exchange: panacea or problem?

PMID- 9269198
TI  - The US attack on Cuba's health.

PMID- 9269199
TI  - The case for "a case of ....".

PMID- 9269200
TI  - In the shadow of plenty, Cuba copes with a crippled health care system.

PMID- 9269201
TI  - Cyclosporiasis: another emerging pathogen comes ashore.

PMID- 9269202
TI  - His own private hospital.
AB  - Dr. Brian Day had a simple solution when it became increasingly difficult to book
      operating room time in Vancouver. He built his own hospital. The Cambie Surgical
      Centre, which treats patients from BC and around the world, has 2 main operating
      rooms, 10 recovery beds and 5 private rooms for extended stays. "What I've done,"
      says Day, "is say that if there are no operating rooms at UBC, I'll build my
      own."

PMID- 9269203
TI  - Does doctors' own fear of dying hinder palliative care?
AB  - Humans have a deeply rooted, existential fear of death that lurks suppressed in
      their unconscious most of the time. Dr. Balfour Mount, a palliative care
      specialist, thinks this is one of the factors preventing the health care system
      from providing good and compassionate care for the dying.

PMID- 9269204
TI  - Time to "rethink models of medical education," ACMC meeting told.

PMID- 9269205
TI  - The web of information inequality.

PMID- 9269206
TI  - When should ACE inhibitors be given to normotensive patients with IDDM.

PMID- 9269207
TI  - Predicting ARDS: problems and prospects.

PMID- 9269208
TI  - "AT risk" for breast cancer.

PMID- 9269209
TI  - Unanswered questions in carcinoma of the testis.

PMID- 9269210
TI  - Misuse of natural hormones in sport.

PMID- 9269211
TI  - Priorities in tropical medicine.

PMID- 9269212
TI  - Randomised placebo-controlled trial of lisinopril in normotensive patients with
      insulin-dependent diabetes and normoalbuminuria or microalbuminuria. The EUCLID
      Study Group.
AB  - BACKGROUND: Renal disease in people with insulin-dependent diabetes (IDDM)
      continues to pose a major health threat. Inhibitors of angiotensin-converting
      enzyme (ACE) slow the decline of renal function in advanced renal disease, but
      their effects at earlier stages are unclear, and the degree of albuminuria at
      which treatment should start is not known. METHODS: We carried out a randomised,
      double-blind, placebo-controlled trial of the ACE inhibitor lisinopril in 530 men
      and women with IDDM aged 20-59 years with normoalbuminuria or microalbuminuria.
      Patients were recruited from 18 European centres, and were not on medication for
      hypertension. Resting blood pressure at entry was at least 75 and no more than 90
      mm Hg diastolic, and no more than 155 mm Hg systolic. Urinary albumin excretion
      rate (AER) was centrally assessed by means of two overnight urine collections at
      baseline, 6, 12, 18, and 24 months. FINDINGS: There were no difference in
      baseline characteristics by treatment group; mean AER was 8.0 micrograms/min in
      both groups; and prevalence of microalbuminuria was 13% and 17% in the placebo
      and lisinopril groups, respectively. On intention-to-treat analysis at 2 years,
      AER was 2.2 micrograms/min lower in the lisinopril than in the placebo group, a
      percentage difference of 18.8% (95% CI 2.0-32.7, p = 0.03), adjusted for baseline
      AER and centre, absolute difference 2.2 micrograms/min. In people with
      normoalbuminuria, the treatment difference was 1.0 microgram/min (12.7% [-2.9 to
      26.0], p = 0.1). In those with microalbuminuria, however, the treatment
      difference was 34.2 micrograms/min (49.7% [-14.5 to 77.9], p = 0.1; for
      interaction, p = 0.04). For patients who completed 24 months on the trial, the
      final treatment difference in AER was 38.5 micrograms/min in those with
      microalbuminuria at baseline (p = 0.001), and 0.23 microgram/min in those with
      normoalbuminuria at baseline (p = 0.6). There was no treatment difference in
      hypoglycaemic events or in metabolic control as assessed by glycated haemoglobin.
      INTERPRETATION: Lisinopril slows the progression of renal disease in normotensive
      IDDM patients with little or no albuminuria, though greatest effect was in those
      with microalbuminuria (AER > or = 20 micrograms/min). Our results show that
      lisinopril does not increase the risk of hypoglycaemic events in IDDM.

PMID- 9269213
TI  - Prevalence and severity of cognitive impairment with and without dementia in an
      elderly population.
AB  - BACKGROUND: Not all cognitively impaired people have dementia, but those who do
      not meet current criteria for dementia have received little study. We report a
      comprehensive estimate of the prevalence of "cognitive impairment, no dementia"
      (CIND) in an elderly population. METHODS: The Canadian Study of Health and Aging
      gathered population representation information about elderly Canadians aged 65
      and over from 36 cities and surrounding areas in five regions. In each region,
      the sample size was 1800 people in the community and 250 people in institutions.
      Patients in the community were screened for cognitive impairment by means of the
      modified mini-mental state examination. Those who scored below the cut-off point
      (n = 1106) and a randomly selected sample of those who scored above the cut-off
      point (n = 494) were referred for clinical examination. 59 individuals unable to
      take the screening test were also assessed clinically. We selected 17 long-term
      care institutions in each region, and then randomly selected consenting residents
      of these institutions for clinical assessment (n = 1255). RESULTS: The prevalence
      of CIND was 16.8%, which was more than all types of dementia combined (8.0%). The
      prevalence of all types of cognitive impairment, including dementias, increased
      with age. Patients with CIND were three times more likely to be living in
      institutions than were cognitively unimpaired patients (odds ratio 3-1 [95% CI
      2.4-3.9]). Circumscribed memory loss has a prevalence of 5.3% in the elderly
      Canadian population, and was the most common category. CIND was related to some
      degree of functional impairment in elderly patients. INTERPRETATION: CIND is
      commonly associated with functional disability and a need for institutional care.
      This diagnostic category includes a costly group of disorders that merit further
      study.

PMID- 9269214
TI  - Effectiveness of needle-exchange programmes for prevention of HIV infection.
AB  - BACKGROUND: Needle-exchange programmes (NEPs) are potentially a key strategy for
      containing the spread of HIV infection among injecting drug users, but their
      implementation has been limited by uncertainty about their effectiveness. We used
      an ecological study design to compare changes over time in HIV seroprevalence in
      injecting drug users worldwide, for cities with and without NEPs. METHODS:
      Published reports of HIV seroprevalence in injecting drug users were identified,
      and unpublished information on HIV seroprevalence for injecting drug users
      entering drug treatment in the USA between 1988 and 1993 was obtained from the
      Centers for Disease Control and Prevention. Details of the implementation of NEPs
      were obtained from published reports and experts. For each of the 81 cities with
      HIV seroprevalence data from more than 1 year and NEP implementation details, the
      rate of change of seroprevalence was estimated by regression analysis. The
      average difference in this rate for cities with and without NEPs was calculated.
      FINDINGS: On average, seroprevalence increased by 5.9% per year in the 52 cities
      without NEPs, and decreased by 5.8% per year in the 29 cities with NEPs. The
      average annual change in seroprevalence was 11% lower in cities with NEPs (95% CI
      -17.6 to -3.9, p = 0.004). INTERPRETATION: A plausible explanation for this
      difference is that NEPs led to a reduction in HIV incidence among injecting drug
      users. Despite the possibility of confounding, our results, together with the
      clear theoretical mechanisms by which NEPs could reduce HIV incidence, strongly
      support the view that NEPs are effective.

PMID- 9269215
TI  - Case-control study of the role of nutritional rickets in the risk of developing
      pneumonia in Ethiopian children.
AB  - BACKGROUND: Pneumonia is the most important cause of morbidity and mortality in
      children aged under 5 years worldwide. Studies in developing countries have
      suggested an association between nutritional rickets and pneumonia. Since both
      nutritional rickets and pneumonia are common in Ethiopia, we did a case-control
      study to determine the role of nutritional rickets in the development of
      pneumonia. METHODS: Cases were children younger than 5 years admitted to the
      Ethio-Swedish Children's Hospital during a 5-year period with a diagnosis of
      pneumonia (n = 521), but data were incomplete for 21 of these and they were not
      included. Controls (n = 500) were matched for admission within 3 months of cases
      and age within 3 months and had no evidence of pneumonia. Nutritional,
      demographic, and clinical and radiographic data for rickets and pneumonia were
      collected. Matched odd ratios and logistic regression were used to test the
      significance of the association of rickets and pneumonia. FINDINGS: Rickets was
      present in 210 of 500 cases compared with 20 of 500 controls (odds ratio 22.11).
      There were significant differences between cases and controls for family size,
      birth order, crowding, and months of exclusive breastfeeding (p < 0.05). After
      correction for these confounding factors by logistic regression, there was still
      a 13-fold higher incidence of rickets among children with pneumonia than among
      controls (13.37 [95% CI 8.08-24.22], p < 0.001). INTERPRETATION: Vitamin D or
      calcium deficiency may be important predisposing factors for pneumonia in
      children aged under 5 years in developing countries. Efforts to prevent vitamin D
      deficiency or calcium supplementation may result in significant reductions in
      morbidity and mortality from pneumonia in these children.

PMID- 9269216
TI  - Measurement of acetylcholinesterase by positron emission tomography in the brains
      of healthy controls and patients with Alzheimer's disease.
AB  - BACKGROUND: Acetylcholinesterase activity, a marker for degeneration of the
      central cholinergic system, has consistently been reported, in necropsy brain
      studies, to be reduced in the cerebral cortex of patients with Alzheimer's
      disease. We have shown regional acetylcholinesterase activity in vivo in rodent
      and primate brains with radioactive acetylcholine analogues. In the present
      study, we used one of the analogues to map acetylcholinesterase activity in the
      brains of living people. METHODS: Positron emission tomography (PET) and a
      radiolabelled acetylcholine analogue with high hydrolytic specificity to
      acetylcholinesterase [11C]N-methyl-4-piperidyl acetate (MP4A), was used in eight
      elderly healthy controls and five patients with Alzheimer's disease who had mild
      dementia. All participants were given an intravenous injection of [11C]MP4A and
      then sequential patterns of radioactivity in various brain regions were obtained
      by PET. Time courses of [11C]MP4A concentration in arterial blood were also
      measured to obtain an input function. A three-compartment model was used to
      estimate regional acetylcholinesterase activity in the brain. FINDINGS: The
      estimated acetylcholinesterase distribution in the brain of the control
      participants agreed with the acetylcholinesterase distribution at necropsy. All
      patients with Alzheimer's disease had multiple cortical regions with a reduced
      estimated acetylcholinesterase activity in comparison with control participants.
      The reduction was more pronounced in the parietotemporal cortex, with an average
      reduction rate of 31% in temporal and 38% in parietal cortex, and less pronounced
      in other cortical lesions (19% in frontal, 24% in occipital, and 20% in
      sensorimotor cortex). Each patient was found to have at least two cortical
      regions with significantly reduced acetylcholinesterase activity. INTERPRETATION:
      The method we describe for non-invasive in-vivo detection of regional
      acetylcholinesterase changes in the living human brain that is feasible for
      biochemical assessment of Alzheimer's disease.

PMID- 9269217
TI  - A hypertensive toddler.

PMID- 9269218
TI  - Concentrations of dioxin 20 years after Seveso.

PMID- 9269219
TI  - Molecular diagnosis of Wilson's disease.

PMID- 9269220
TI  - Coronary stenosis dilatation induced by L-arginine.

PMID- 9269222
TI  - Protein kinase C expression in salivary gland acinar epithelial cells in
      Sjogren's syndrome.

PMID- 9269221
TI  - Borna disease virus in brains of North American and European people with
      schizophrenia and bipolar disorder. Bornavirus Study Group.

PMID- 9269223
TI  - 5-HT2A receptor polymorphism and steady state receptor expression in
      schizophrenia.

PMID- 9269224
TI  - Healing of duodenal ulcer after eradication of Helicobacter heilmannii.

PMID- 9269225
TI  - Vero-cytotoxin-producing Escherichia coli O157 in a farmer handling horses.

PMID- 9269226
TI  - FDA warns of potential protease-inhibitor link to hyperglycaemia.

PMID- 9269227
TI  - Cholera.

PMID- 9269228
TI  - Gulf War syndrome: is it due to a systemic shift in cytokine balance towards a
      Th2 profile?
AB  - The symptoms of Gulf War syndrome are compatible with the hypothesis that the
      immune system of affected individuals is biased towards a Th2-cytokine pattern.
      Factors that could lead to a Th2 shift among Gulf War veterans include exposure
      to multiple Th2-inducing vaccinations under stressful circumstances and the way
      in which such vaccinations were administered, which would be expected to maximise
      Th2 immunogenicity. These factors may have led to a long-term systemic shift
      towards a Th2-cytokine balance and to mood changes related to the immunoendocrine
      state. Other vaccines that lead to similar long-term, non-specific shifts in
      cytokine balance are well-established. If our hypothesis is proven, treatment may
      be possible with regimens that induce a systemic Th1 bias.

PMID- 9269229
TI  - Health services research: saviour or chimera?

PMID- 9269230
TI  - British HIV Association guidelines for antiretroviral treatment of HIV
      seropositive individuals.

PMID- 9269231
TI  - British HIV Association guidelines for antiretroviral treatment of HIV
      seropositive individuals.

PMID- 9269232
TI  - British HIV Association guidelines for antiretroviral treatment of HIV
      seropositive individuals.

PMID- 9269233
TI  - British HIV Association guidelines for antiretroviral treatment of HIV
      Seropositive individuals.

PMID- 9269234
TI  - An unusual case of steatorrhoea.

PMID- 9269235
TI  - Effect of renal-artery stenting on progression of renovascular renal failure.

PMID- 9269236
TI  - Effect of renal-artery stenting on progression of renovascular renal failure.

PMID- 9269237
TI  - Effect of renal-artery stenting on progression of renovascular renal failure.

PMID- 9269238
TI  - Relapse of depression after rapid depletion of tryptophan.

PMID- 9269239
TI  - Threat of dengue haemorrhagic fever after yellow fever vaccination.

PMID- 9269240
TI  - Growth hormone in end-stage heart failure.

PMID- 9269241
TI  - Growth hormone in end-stage heart failure.

PMID- 9269242
TI  - Growth hormone in end-stage heart failure.

PMID- 9269243
TI  - Screening test for coeliac disease.

PMID- 9269244
TI  - Vitamin trials and cancer.

PMID- 9269245
TI  - Optimum dose of digoxin.

PMID- 9269246
TI  - Optimum dose of digoxin.

PMID- 9269247
TI  - On being the right size: a reappraisal of mammography trials in Canada and
      Sweden.

PMID- 9269248
TI  - Mental illness may be damaging to your brain.

PMID- 9269249
TI  - Discontinuation symptoms after treatment with serotonin reuptake inhibitors: a
      literature review.
AB  - BACKGROUND: The discontinuation of many pharmacologic agents is associated with
      characteristic withdrawal symptoms. Antidepressants, particularly the tricyclic
      antidepressants (TCAs), are known to be associated with a group of common
      symptoms upon discontinuation. Serotonin reuptake inhibitors (SRIs) are also
      taking their respective place in the literature with reports of discontinuation
      symptoms. This review summarizes case reports and reports that allow systematic
      assessment of discontinuation symptoms following SRI discontinuation. METHOD: A
      computerized literature search was conducted using a MEDLINE search to identify
      reports of withdrawal effects following discontinuation of SRIs. Additional
      reports were found in the bibliographies of various published reports. RESULTS:
      SRI discontinuation symptoms in adults are summarized in 24 case reports and 9
      reports from controlled clinical trials. Additionally, 3 case reports addressing
      SRI discontinuation in the neonate are described. The reports describe clusters
      of symptoms commonly associated with the discontinuation of an SRI. CONCLUSION:
      We propose to define an antidepressant discontinuation syndrome as the onset of a
      cluster of somatic and psychic symptoms following the discontinuation of an SRI
      and not attributable to other causes (e.g., concomitant medication, illness).
      These symptoms include dizziness, light-headedness, insomnia, fatigue,
      anxiety/agitation, nausea, headache, and sensory disturbance. The syndrome may
      last up to 3 weeks and may be improved by restarting the antidepressant or
      starting an antidepressant with a similar pharmacologic profile.

PMID- 9269250
TI  - Predicting the short-term outcome of first episodes and recurrences of clinical
      depression: a prospective study of life events, difficulties, and social support
      networks.
AB  - BACKGROUND: The study employed interview-based, investigator-rated measures of
      symptoms and psychosocial adversity in a panel survey to predict clinical course
      of depression. METHOD: 130 men and women attending psychiatric hospitals for
      episodes of depressive disorders were interviewed with the Present State
      Examination and Life Events and Difficulties Schedule. After a mean 4-month
      interval, 119 were successfully reassessed to test the hypothesis that recovery
      from clinical depression is related to rates of life event stress and
      difficulties (termed psychosocial adversity) in the 6 to 12 months preceding
      initial evaluation. RESULTS: The severity (p < .01) and the duration (p < .01) of
      the episode of depression up until the initial evaluation emerged as the only
      significant background predictors of episode severity at later follow-up. High
      levels of adversity were significantly (p < .05) related to a poor clinical
      course, due to failure to recover from first-onset and from second episodes.
      Recovery from all but first episodes was predicted by higher levels of social
      support rated at initial attendance. There was no evidence for the buffering of
      the harmful effects of adversity by larger, more connected social support
      networks. CONCLUSION: Both life event stress and support network characteristics
      are associated with the short-term outcome of depressive episodes. The findings
      for social support in particular confirm growing evidence of the importance of
      distinguishing between early and later relapsing episodes in causal
      investigations of depression. They reveal a progressive vulnerability to deficits
      in social circumstances with advancing course of disorder.

PMID- 9269251
TI  - Rapid conversion from one monoamine oxidase inhibitor to another.
AB  - BACKGROUND: Numerous sources state that switching from one monoamine oxidase
      (MAO) inhibitor to another can be done only after a 14-day washout period. In
      hospitalized patients and severely depressed outpatients, such a wait may be
      impracticable. METHOD: We reviewed the case histories of eight consecutive and
      random patients whom we converted from one MAO inhibitor to another within less
      than the recommended waiting period. RESULTS: Only one patient experienced
      troubling adverse effects, and these effects were brief and time-limited. The
      patient's symptoms were indicative of either withdrawal from tranylcypromine or a
      mild serotonin syndrome. All other patients tolerated the conversion well with
      minimal or no adverse effects. Four of the eight patients eventually responded to
      the new MAO inhibitor. CONCLUSION: These results suggest that some patients can
      be cautiously but rapidly switched from one MAO inhibitor to another without
      prolonged drug-free periods. Unquestionably, this strategy should be used only
      when the clinical picture mandates a rapid conversion. Further, it should be
      reserved for those patients with established high compliance and should include
      close monitoring and the use of a low-tyramine diet. Extreme caution must still
      be undertaken in utilizing this approach until larger studies more accurately
      determine the frequency of serious adverse effects.

PMID- 9269252
TI  - Risperidone in the elderly: a pharmacoepidemiologic study.
AB  - BACKGROUND: The possibly limited adverse effects of risperidone encourage
      interest in its use in geriatric patients. METHOD: Medical records of 122
      hospitalized psychogeriatric patients (> or = 65 years old) newly treated with
      risperidone were reviewed and scored for indications, doses, and effects of this
      novel neuroleptic. RESULTS: Subjects (83 women, 39 men), mean +/- SD age = 76.5
      +/- 6.8 years (range, 65-95), were given risperidone for agitation or psychosis
      associated with dementia (53%), a major mood disorder (29%), or other disorders
      (18%). Most (77%) were also medically ill and received other psychotropic (76%)
      or cardiovascular agents (70%). Daily doses of risperidone averaged 1.6 +/- 1.1
      mg (range, 0.25-8.0) (0.025 mg/kg body wt.); 78% received 2.0 mg. Risperidone
      appeared to be effective in 85% of cases, but 18% were discontinued due to
      intolerability (11%) or inefficacy (7%). Adverse events occurred in 32% of the
      patients (36% of those discontinued). These adverse events included hypotension
      (29%) or symptomatic orthostasis (10%), cardiac arrest (1.6%) with fatality
      (0.8%), and extrapyramidal effects (11%) or delirium (1.6%). Benefits were
      associated with younger age and male gender, but not risperidone dose. Adverse
      effects were associated with cardiovascular disease and its treatment,
      cotreatment with an SRI antidepressant or valproate, and relatively rapid dose
      increases. CONCLUSION: Risperidone appeared to be effective and may be safe for
      many elderly psychiatric patients with comorbid medical conditions provided that
      doses are low and increased slowly. Particular caution is advised in the presence
      of cardiovascular disease or cotreatment with other psychotropic agents.

PMID- 9269253
TI  - Clozapine treatment for neuroleptic-induced tardive dyskinesia, parkinsonism, and
      chronic akathisia in schizophrenic patients.
AB  - BACKGROUND: Previous studies on the use of clozapine in neuroleptic-resistant
      chronic schizophrenic patients have demonstrated positive effects on tardive
      dyskinesia but were less conclusive about chronic akathisia and parkinsonism. The
      aim of the present study was to investigate the short-term (18 weeks) efficacy of
      clozapine in neuroleptic-resistant chronic schizophrenic patients with coexisting
      tardive dyskinesia, chronic akathisia, and parkinsonism. METHOD: Twenty chronic,
      neuroleptic-resistant schizophrenic patients with coexisting tardive dyskinesia,
      parkinsonism, and chronic akathisia were treated with clozapine. Assessment of
      tardive dyskinesia, parkinsonism, and chronic akathisia was made once weekly for
      18 weeks with the Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus
      Rating Scale for Extrapyramidal Side Effects, and Barnes Rating Scale for Drug
      Induced Akathisia (BAS). RESULTS: At the end of 18 weeks of clozapine treatment,
      improvement rates were 74% for tardive dyskinesia, 69% for parkinsonism, and 78%
      for chronic akathisia. A statistically significant reduction in the scores on the
      AIMS and Simpson-Angus Scale was achieved at Week 5 and on the BAS at Week 6 (p <
      .0001). CONCLUSION: Relatively low doses of clozapine are effective for the
      treatment of neuroleptic-induced extrapyramidal syndromes in neuroleptic
      resistant chronic schizophrenic patients. The relief of tardive dyskinesia,
      parkinsonism, and chronic akathisia in this group of patients occurs more rapidly
      than the reduction in psychotic symptoms. Disturbing, long-term extrapyramidal
      syndromes in chronic schizophrenic patients should be considered an indication
      for clozapine treatment.

PMID- 9269254
TI  - Severe extrapyramidal reaction due to risperidone in a case of neurofibromatosis.

PMID- 9269255
TI  - Behavior therapy and serotonin dysregulation.

PMID- 9269256
TI  - Antidepressant effects of nicotine.

PMID- 9269257
TI  - Panic and paranoia.

PMID- 9269258
TI  - Switching drug class after initial SSRI failure.

PMID- 9269259
TI  - Nizatidine-induced delirium in a nonagenarian.

PMID- 9269260
TI  - Obsessive-compulsive disorder in pregnancy, the puerperium, and the premenstruum.
AB  - BACKGROUND: Recent reports suggest that pregnancy and the puerperium may
      precipitate or exacerbate obsessive-compulsive disorder (OCD). The influence of
      this illness on other reproductive events, such as the premenstruum, is unknown.
      We examined retrospectively the relationships of pregnancy, the puerperium, and
      premenstruum to the course of OCD in 57 women. METHOD: Women outpatients with OCD
      meeting DSM-III-R criteria completed a standardized telephone interview
      administered by a psychiatric resident. They were asked retrospectively about the
      clinical course of their illness premenstrually and during and after pregnancy.
      RESULTS: Of 72 women eligible for the study, 79% (N = 57) completed the
      interview. Premenstrual worsening of OCD was described by 24 (42%) of the 57
      women, and 12 (21%) described premenstrual dysphoria. Of the 57 women, 38 (67%)
      had been pregnant at least once; 31 (54%) had delivered at least one child.
      Pregnancy was associated with the onset of OCD in only 5 (13%) of the 38 women.
      Of the 29 women with preexisting OCD who became pregnant, 20 (69%) described no
      change in symptoms during pregnancy, 5 (17%) described worsening, and 4 (14%)
      described improvement. Postpartum exacerbation of OCD symptoms was reported by 7
      (29%) of the 24 women with preexisting OCD who completed full-term pregnancies.
      Nine (37%) of the 24 women with both preexisting OCD and completed pregnancies
      also reported postpartum depression. CONCLUSION: The premenstrual and postpartum
      exacerbation of OCD symptoms in some women suggests that the course of this
      disorder may, in some cases, be influenced by changes in gonadal hormones. Our
      finding that women with OCD may be at increased risk for postpartum depression
      underscores the importance of careful postpartum evaluation of women with OCD to
      prevent maternal and infant morbidity.

PMID- 9269261
TI  - Antibiotic use or misuse?

PMID- 9269262
TI  - Chewing over temporomandibular disorders.

PMID- 9269263
TI  - Phytoestrogens: emerging multifaceted plant compounds.

PMID- 9269264
TI  - Clopidogrel: a new safe and effective antiplatelet agent. But unanswered
      questions remain.

PMID- 9269265
TI  - Antibiotic use in the Australian community, 1990-1995.
AB  - OBJECTIVE: To determine the pattern of antibiotic use in the Australian
      community, 1990-1995, and compare it with the pattern in other developed
      countries. DESIGN: Survey of data from the national database on drugs dispensed
      in Australia (1990-1995), an international database on retail drug sales (1985
      1994), and Australian prescriber surveys (1994, 1995). MAIN OUTCOME MEASURES:
      National and international retail sales of oral antibiotics (defined daily doses
      [DDDs]/1000 population/day) and antibiotic prescriptions dispensed through
      community pharmacies by drug type; antibiotic prescribing profiles for common
      conditions. RESULTS: Antibiotic use in Australia remained steady between 1990 and
      1995, with an estimated 24.7 DDDs/1000 population/day dispensed through community
      pharmacies in 1990 and 24.8 DDDs/1000 population/day in 1995. Amoxycillin,
      although declining in use, remained the most dispensed antibiotic. Compared with
      the other countries surveyed, Australia had the highest percentage use of
      tetracyclines, such as doxycycline, and the lowest percentage use of
      fluoroquinolones. Use of trimethoprim-sulfamethoxazole and flucloxacillin
      declined in Australia. In new cases of upper respiratory tract infection or
      pharyngitis, an antibiotic prescription was recorded for 57% of urban patient
      encounters and 73% of rural patient encounters. CONCLUSIONS: Antibiotic use in
      Australia is high, as in many other developed countries, but did not increase
      between 1990 and 1995. The overall profile of antibiotic use in Australia by drug
      class was similar to that in the United Kingdom. Antibiotics were still commonly
      prescribed for upper respiratory tract infection (which is usually viral), more
      commonly by rural than by urban general practitioners.

PMID- 9269266
TI  - The public health impact of dog attacks in a major Australian city.
AB  - OBJECTIVE: To examine the impact of dog attacks by determining the incidence and
      risk factors for dog attacks. DESIGN: Injury surveillance data on dog attacks for
      a major metropolitan hospital were converted to incidence rates using 1991 census
      figures for the hospital catchment area and combined with data on community
      attitudes and experiences derived from a large community survey. SETTING: Queen
      Elizabeth Hospital (tertiary referral hospital), Adelaide, South Australia,
      January 1990 to July 1993. PARTICIPANTS: 356 victims of dog attacks who presented
      to the emergency department and 3093 respondents to the 1992 South Australian
      Health Omnibus Survey. MAIN OUTCOME MEASURES: Rates of dog attack by age and sex
      of the victim, hospital presentation and admission; differences in the
      representation of various dog breeds in attacks. RESULTS: About 6500 people are
      injured in Adelaide each year as a result of dog attacks and about 810 seek
      hospital treatment (7.3 per 10,000 people per year). Children aged 0-4 years were
      attacked and required hospital treatment twice as often as adults aged 21-59
      years, and men aged over 76 years twice as often as men aged 36-75 years. Males
      were more at risk of attack than females for all age groups. Hospital admission
      rates were five times higher for the elderly (95% confidence interval [CI], 2.3%
      10.2%) and seven times higher for children 12 years and under (95% CI, 3.4%
      15.1%) compared with people aged 13-59 years; 90% of children were admitted
      because of head and facial bites. The risk of attack from german shepherds, bull
      terriers, blue/red heelers, dobermans and rottwellers was four to five times
      higher than for other common breeds. CONCLUSIONS: The public health implications
      of dog attacks are significant and there needs to be increased awareness of the
      risks to young children. Potential interventions to reduce the incidence of dog
      attacks vary from strict controls on high-risk breeds to mandatory leashing to a
      "user pays" liability insurance proposal.

PMID- 9269267
TI  - Copper-salicylate gel for pain relief in osteoarthritis: a randomised controlled
      trial.
AB  - OBJECTIVE: To assess the efficacy and safety of a copper-salicylate gel in
      osteoarthritis of the hip and knee. DESIGN: Randomised, double-blind, placebo
      controlled study. SETTING: Rheumatology Clinic of St Vincent's Hospital, Sydney,
      New South Wales (a tertiary referral hospital), June 1993 to October 1994.
      PATIENTS: 116 patients with pain associated with osteoarthritis of the hip and/or
      knee (diagnosed by criteria of the European League against Rheumatism), drawn
      from patients attending the Clinic or self-referred after newspaper
      advertisements. INTERVENTION: Copper-salicylate or placebo gel (1.5 g) applied
      twice daily to the forearm for four weeks. OUTCOME MEASURES: Self-assessment of
      pain before the trial and after two and four weeks of treatment; patient and
      investigator assessments of efficacy; additional analgesia required; adverse
      reactions; and withdrawal rates. RESULTS: Pain scores at rest and on movement
      decreased in both the copper-salicylate and placebo groups by 13%-20%. There was
      no significant difference between the two groups for decrease in pain score,
      patient and investigator efficacy ratings, number of patients requiring
      paracetamol for extra analgesia (active, 77%; placebo, 71%) and average dose of
      paracetamol (active, 555 mg/day; placebo, 600 mg/day). Significantly more
      patients in the copper-salicylate group reported adverse reactions (83% versus
      52% of the placebo group), most commonly skin reactions, and withdrew from the
      trial because of these reactions (17% versus 1.7% of the placebo group).
      CONCLUSION: Copper-salicylate gel applied to the forearm was no better than
      placebo gel as pain relief for patients with osteoarthritis of the hip or knee,
      but produced significantly more skin rashes.

PMID- 9269268
TI  - Phytoestrogens and prostate cancer: possible preventive role.
AB  - Phytoestrogens are biologically active plant compounds with both oestrogenic and
      antioestrogenic actions, and communities whose diets are rich in phytoestrogens
      have a lower incidence of prostate cancer. A 66-year-old man took phytoestrogen
      160 mg (4 x 40-mg tablets) daily for one week before radical prostatectomy for
      moderately high-grade adenocarcinoma. The resected specimen showed prominent
      apoptosis, typical of a response to high-dose oestrogen therapy and suggestive of
      tumour regression. There were no adverse side effects. Studies of the effects of
      phytoestrogens in prostate cancer may be warranted.

PMID- 9269269
TI  - Health care. A model for the management of self-poisoning.
AB  - OBJECTIVE: To describe the development and activity of a multidisciplinary
      service to manage self-poisoning. DESIGN: Descriptive, comparative study with
      prospective data collection. SETTING: Regional toxicology treatment centre in the
      Hunter area of New South Wales (NSW) with primary and secondary referral service
      to 385,000 people and tertiary referral service to a further 100,000. PATIENTS:
      All patients (1987-1995) with poisoning or envenomation presenting to the Hunter
      Area Toxicology Service (HATS). MAIN OUTCOME MEASURES: Average length of stay for
      HATS compared with national and NSW hospitals; mortality data for HATS compared
      with NSW. RESULTS: Average length of stay for HATS was 0.53-1.22 days shorter
      than for all Australian hospitals, potentially saving 518 bed-days, valued at
      $468,000 per year. Average length of stay was 0.94-3.39 days shorter than for all
      NSW hospitals, saving 1470 bed-days at $1.4 million per year. Inpatient mortality
      (0.2%; 95% confidence interval, 0.0-1.1) was not significantly different from NSW
      (0.5%; 95% CI, 0.2-0.8). Standardised mortality ratios showed no greater all
      cause suicide mortality. CONCLUSIONS: In our centralised model for managing self
      poisoning, all toxicology patients in an area health service are diverted to one
      hospital, where all patients with deliberate self-poisoning are admitted under
      the one multidisciplinary team, and all receive psychiatric assessment. This
      model has substantially reduced bed stay, with considerable savings to the Hunter
      Area Health Service manifested as an increase in beds available for other
      purposes.

PMID- 9269270
TI  - The essential practice of mental health care.

PMID- 9269271
TI  - Psychiatric assessment in community practice.

PMID- 9269272
TI  - Asthma in adults.

PMID- 9269273
TI  - Laparoscopic and abdominal hysterectomy: a cost comparison.

PMID- 9269274
TI  - Laparoscopic and abdominal hysterectomy: a cost comparison.

PMID- 9269275
TI  - Laparoscopic hysterectomy.

PMID- 9269276
TI  - Caution with post-treatment test-of-cure for genital Chlamydia.

PMID- 9269277
TI  - Ciprofloxacin-resistant Salmonella typhi: an emerging problem.

PMID- 9269278
TI  - Neurological manifestations of kava intoxication.

PMID- 9269280
TI  - Munchausen's syndrome by proxy.

PMID- 9269279
TI  - Balloon-induced latex anaphylaxis.

PMID- 9269281
TI  - Methadone-related deaths in New South Wales.

PMID- 9269282
TI  - Irradiation for pterygia.

PMID- 9269283
TI  - What's in a name?

PMID- 9269284
TI  - What's in a name?

PMID- 9269285
TI  - Amaurosis fugax treated with nifedipine.

PMID- 9269286
TI  - Neutropenia alert cards.

PMID- 9269287
TI  - The hospital management of community acquired pneumonia in adults.

PMID- 9269288
TI  - Vesicoureteric reflux and reflux nephropathy: the Christchurch contribution.
AB  - For the past 40 years members from the Christchurch departments of paediatrics,
      nephrology, radiology, pathology and nuclear medicine have studied the entity of
      vesicoureteric reflux and its main complication of reflux nephropathy. Initially
      the natural history of vesicoureteric reflux was examined by investigating 350
      infants with urinary infection by intravenous urography and micturating
      cystourethrography. The 40% demonstrating reflux were followed up for
      approximately 12 years. The study showed that infancy and early childhood were
      the critical periods for renal damage to occur, that the damage was confined to
      those kidneys subjected to severe degrees of reflux, that lesser degrees of
      reflux were not associated with renal damage and that a spontaneous lessening of
      the severity of reflux occurred with increasing age. Other aspects of reflux
      nephropathy also have been studied including pathogenic mechanisms resulting in
      renal damage, ultrasonography to examine fetal anatomy, radioisotopic methods for
      demonstrating renal scarring and reflux, and the long term follow up of adults
      with reflux nephropathy.

PMID- 9269289
TI  - Vaccine adverse events reported in New Zealand 1990-5.
AB  - AIM: New Zealand monitors vaccine safety through vaccinator reports of adverse
      events following immunisation. The rate of reporting for the commonly used
      vaccines during 1990-5 are presented. During this time new vaccines were added to
      the immunisation schedule, enabling comparison of reporting rates. METHOD: The
      number of events were obtained from the CARM database and a rate calculated based
      on estimated vaccine use. RESULTS: Injection site reaction with adult tetanus
      diphtheria vaccine was most commonly reported (68/100,000); a rate five times
      higher than with tetanus vaccine. There were also more reported reactions from
      diphtheria-tetanus-pertussis-Haemophilus influenzae type b (DTPH) than DTP
      vaccine, with 'abnormal crying' the commonest reaction reported after 29/100,000
      doses of DTPH and 3/100,000 doses of DTP. The next commonest reaction for DTPH
      was injection site reaction (25/100,000) which compares to 17/100,000 doses of
      DTP. For the other inactivated vaccines, more reports were made for fever
      following Hib (16/100,000), than for hepatitis B (2/100,000) or influenza
      (1/100,000). The most common reports following measles-mumps-rubella (MMR)
      vaccine were rash (17/100,000), fever (12/100,000), and injection site
      inflammation (5/100,000). There were very few reports following polio vaccine,
      with rash, fever and headache all reported at less than 1/100,000 doses.
      CONCLUSION: Although only a proportion of events are reported, the picture
      presented here confirms the overall safety of vaccines and the value of the
      adverse event monitoring system. Monitoring vaccine adverse events is an
      essential part of the immunisation programme.

PMID- 9269290
TI  - Characteristics of patients admitted to hospital with chronic obstructive
      pulmonary disease.
AB  - AIMS: To examine the characteristics of patients admitted to Auckland Hospital
      with chronic obstructive pulmonary disease (COPD) and to assess their management
      prior to hospitalisation. METHODS: Prospective survey of 99 patients admitted
      with COPD over an 8 week period. Of these, 80 patients were interviewed about
      their social circumstances, physical functioning, smoking habits and medical
      treatment. They also had their inhaler technique checked and FEV1 measured.
      RESULTS: Subjects had a mean age of 70.6 years with a mean FEV1 of 29% of
      predicted. 45% lived alone and a third still smoked. The mean value for their
      usual physical functioning was 15.4 (possible 10-30) on the SF-36 health status
      questionnaire. 84% of all subjects used a beta-agonist, 50% an anticholinergic
      bronchodilator, 69% inhaled steroids, 18% oral steroids, and 19% theophylline.
      40% used nebulised medication and only 6% had domiciliary oxygen. 40% reported
      having an influenza vaccination in the preceding year and 27% had participated in
      some form of pulmonary rehabilitation. The mean length of stay was 7.5 days.
      CONCLUSIONS: Patients hospitalized for COPD report marked impairment in physical
      functioning, despite which many live alone. They frequently use inhaled and oral
      steroids, and nebulised medication, but only a minority had received an influenza
      vaccination or attended pulmonary rehabilitation.

PMID- 9269291
TI  - Low vitamin D status is common among elderly Dunedin women.
AB  - AIMS: To review vitamin D status and the relationship of serum 25-hydroxyvitamin
      D levels to hip bone mineral density in a group of healthy elderly women living
      independently in their own homes in Dunedin. METHODS: Thirty-eight elderly
      subjects (> 70 years of age) were studied. Serum levels of 25-hydroxyvitamin D
      (25(OH)D) were measured by radioimmunoassay in summer and winter. Femoral neck
      bone mineral density was measured by dual x-ray energy absorptiometry. RESULTS:
      Hip density was correlated with serum 25(OH)D levels at study entry. In summer,
      10 of 38 patients (26.3%) had serum 25(OH)D levels below the reference range for
      healthy adults (40-185 nmol/L). Six patients subsequently withdrew from the
      study. In winter, 22 of the remaining 32 women (68.8%) had serum 25(OH)D values
      below the reference range. Subjects with low 25(OH)D values were given halibut
      oil tablets (400 IU vitamin D3 per day) to improve their serum 25(OH)D levels.
      CONCLUSIONS: Vitamin D deficiency is common among elderly women with a high risk
      of fracture who live in southern New Zealand. This is most marked in the winter
      months. Vitamin D replacement is cheap and effective and should be considered in
      patients over 70 years of age who have a high risk of fracture and who live in
      temperate climates.

PMID- 9269292
TI  - Nosocomial Trichophyton tonsurans in a long stay ward.
AB  - AIMS: To document a nosocomial outbreak of Trichophyton tonsurans infection in a
      long stay ward. METHOD: Retrospective review of mycology cultures taken from
      patients and staff during 1993-5 and clinical examination of both patients and
      staff. RESULTS: Thirty-three mycology samples from 13 patients and staff,
      cultured T tonsurans during the period 1993-5. Twenty-two patients and staff were
      examined; 4 had mycology confirmed T tonsurans (2 scalp, 2 fingernail). Treatment
      with terbinafine 250 mg/day for 2 months resulted in clinical clearance (only 1
      positive culture in 16 months follow-up). SUMMARY: T tonsurans is emerging as an
      important pathogen which may cause nosocomial infections.

PMID- 9269294
TI  - Cannabis use in young New Zealanders.

PMID- 9269295
TI  - Cannabis use in young New Zealanders.

PMID- 9269293
TI  - Measles susceptibility in a university student population.

PMID- 9269296
TI  - Cytokine receptor signal transduction through Jak tyrosine kinases and Stat
      transcription factors.
AB  - Cytokines are the principal regulators of cell proliferation and differentiation
      of hematopoietic cells and these responses are initiated through activation of
      hematopoietic cytokine receptors. Although the receptor intracellular domains
      lack any kinase domains, activation of cytokine receptors lead to rapid induction
      of tyrosine phosphorylation. Recently, cytokine receptors have been shown to
      associate with and activate members of the cytoplasmic Jak tyrosine kinase
      family. Activation of Jak kinases leads to phosphorylation of several signaling
      proteins and thereby couples ligand-mediated receptor stimulation to activation
      of intracellular signaling pathways. The best characterized substrates for Jaks
      are the Stat transcription factors, which are crucial mediators of cytokine
      mediated gene responses, and, particularly, central determinants for the
      specificity in cytokine responses.

PMID- 9269297
TI  - Characteristics of CD14 shedding from human monocytes. Evidence for the
      competition of soluble CD14 (sCD14) with CD14 receptors for lipopolysaccharide
      (LPS) binding.
AB  - The accumulation of sCD14 shed from human monocytes in vivo might correlate with
      other inflammatory parameters and could be of importance in overcoming a sepsis
      situation. The development of the sCD14 titer in the supernatant of monocyte
      enriched MNC cultures isolated from healthy volunteers was studied utilizing a
      commercially available sCD14 ELISA. These culture experiments revealed the
      prolonged liberation of sCD14 into the supernatant during a period of several
      days. A medium-exchange schedule of 2-3 days was found to be superior to a longer
      incubation period with respect to the sCD14 yield. PMA initially enhanced the
      CD14 shedding slightly, but after a few hours it strongly repressed the process.
      Such a reduction was also achieved by protein synthesis inhibitors
      (cycloheximide, actinomycin D). Additionally, we monitored the concentration of
      sCD14, CRP, IL-6 and IL-8 in human sera from healthy persons or patients
      suffering from severe burn injuries with or without sepsis. Our results indicate
      that sCD14 is strongly correlated with IL-6, but not with IL-8. sCD14 titers were
      higher in the group of patients with both burn injuries and sepsis. From
      experiments with monocyte-enriched MNC cultures isolated from healthy volunteers
      and medium supplemented with sera containing sCD14 as well as radiolabeled LPS,
      we conclude that the enhanced shedding of CD14 in vivo during sepsis is probably
      not able to reduce the binding of LPS to monocytes.

PMID- 9269298
TI  - Differential expression of integrins and laminin-5 in normal oral epithelia.
AB  - beta 1 and beta 4 integrins are receptors on epithelial cells mediating cell
      extracellular matrix adhesion. Furthermore, alpha 2 beta 1 and alpha 3 beta 1
      contribute to cell-cell adhesion. Laminin-5 in epithelial basement membranes
      (BMs) is a ligand for alpha 6 beta 4 and alpha 3 beta 1. Expression of different
      integrins and laminin-5 was studied in oral epithelium to characterize regional
      variations in these adhesion molecules. Monoclonal antibodies directed against
      alpha 2-alpha 6 beta 1/alpha 6 beta 4 and laminin-5 were examined in
      cryopreserved biopsies of normal mucosa by immunohistochemistry. Laminin-5 was
      expressed as a line along the BMs. The junctional epithelium showed a unique
      phenotype: Laminin-5 was detected in the internal BM at the tooth surface and in
      the external BM, where excessive laminin-5 was seen in the stroma. alpha 6 beta 4
      was expressed in all cells of the junctional epithelium. Integrins alpha 4 beta 1
      and alpha 5 beta 1 were not detected in the epithelia, whereas alpha 2 beta 1 and
      alpha 3 beta 1 showed differential expression. Epithelia with well-developed rete
      pegs and connective tissue papillae showed polarized alpha 3 beta 1 expression
      along the BM in the rete pegs, in contrast to negative expression at the tips of
      the connective tissue papillae. A variation in the suprabasal distribution of
      alpha 2 beta 1 and alpha 3 beta 1 was observed between epithelia from different
      regions. alpha 2 beta 1 and alpha 3 beta 1 were detected in basal/parabasal cells
      in keratinized epithelia, whereas there was increased suprabasal expression in
      nonkeratinized mucosa. These results indicate inhomogeneity in the basal cell
      population of oral squamous epithelia and differential expression of integrins,
      which may reflect differences in the underlying stroma. Laminin-5 deposits in the
      stroma underneath the junctional epithelium may indicate subclinical gingival
      inflammation.

PMID- 9269299
TI  - Detection of serum interferon-alpha by dissociation-enhanced lanthanide
      fluoroimmunoassay. Studies of patients with acute viral and bacterial infections.
AB  - A sensitive dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA) was
      evaluated for ability to detect interferon-alpha (IFN-alpha) in serum of patients
      with acute infectious disease of less than one week's duration and a fever of >
      38 degrees C. None of 36 patients with confirmed or probable bacterial disease
      was IFN-alpha positive. In contrast, 13/26 patients with viral infections had
      detectable levels of IFN-alpha in serum, all clearly positive (> or = 10 U/ml).
      The IFN-alpha positive serum samples were obtained early after onset of clinical
      disease, after a mean of 2.4 days. The IFN-alpha positive samples were obtained
      from 10 of the 12 patients with influenza or flu-like infection, and 3 of the 5
      patients with varicella or herpes zoster. The IFN-alpha negative patients with
      viral disease (n = 9) included five patients with mononucleosis. The DELFIA
      should be useful in further studies of the value of IFN-alpha determinations in
      the identification of acute viral infections.

PMID- 9269300
TI  - Expression of GLUT1 in stratified squamous epithelia and oral carcinoma from
      humans and rats.
AB  - Most cells express facilitative glucose transporters. Four isoforms (GLUT1-4)
      transporting D-glucose across the plasma membrane show a specific tissue
      distribution, which is the basis for tissue-specific patterns in glucose
      metabolism. GLUT1 is expressed at high levels in tissue barriers such as the
      blood-brain barrier, and this isoform has been suggested as an indicator of such
      barriers. GLUT1 has been found in basal layers of human epidermis where no such
      tissue barrier is present. To further clarify these issues, we examined the
      distribution of GLUT1 and GLUT4 in skin, different types of oral mucosa from rat
      and man, and a human oral carcinoma by indirect immunofluorescence microscopy.
      The results showed that GLUT1 was expressed in the basal and parabasal layers of
      the different stratified squamous epithelia, with some variations between
      keratinized and non-keratinized subtypes. GLUT1 was also expressed in ductal- and
      myoepithelial cells of minor salivary glands and perineural sheath located in the
      lamina propra, and furthermore in the cells of an oral carcinoma. GLUT4 was not
      expressed in any of the tissues examined. This distribution of GLUT1 does not fit
      with the idea of GLUT1 as a general indicator of tissue barriers. In contrast,
      our results support the prevailing, but limited knowledge of glucose metabolism
      in squamous stratified epithelia, a metabolism believed to depend mostly on
      glycolysis, especially in the basal layers. High-level expression seemed to be
      confined to keratinocytes without glycogen stores.

PMID- 9269302
TI  - Observer variability in histological malignancy grading of adenoid cystic
      carcinomas.
AB  - The value of malignancy grading of adenoid cystic carcinomas (ACC) is
      controversial. Some studies have shown that tumours with a solid growth component
      have a rapid fatal course, compared to tumours without a solid growth component,
      in which recurrences develop even many years after initial treatment. Other
      studies have failed to correlate growth patterns with clinical course. No
      universally accepted grading system exists and no reproducibility studies of the
      existing grading systems have been performed. The aim of this study was to
      examine the reproducibility of grading based on semi-quantitative assessment of
      the solid growth pattern in ACC. Two different grading systems were assessed by 3
      observers on a material of 59 ACC. Interobserver agreement was evaluated using
      the kappa statistic. The reproducibility of grading was poor, except for the
      category "solid component constituting 50% or more of the tumour" (kappa = 0.52).
      It is concluded that quantitative methods are necessary if grading is to be used
      in prognostic evaluation of ACC. The rarity of the tumours, however, combined
      with difficulties in diagnosis will impede such investigations unless multicentre
      studies are undertaken.

PMID- 9269301
TI  - Distribution of adhesion molecules on HeLa cells, platelets and endothelium in an
      in vitro model mimicking the early phase of metastasis. An immunogold electron
      microscopic study.
AB  - The aim of the present study was to obtain information about the distribution of
      various adhesion molecules within and on the surface of HeLa cells, platelets and
      endothelial cells in an in vitro model mimicking the early phase of metastasis.
      Suspensions of HeLa cells and human platelets, added to a medium of cultured
      human umbilical-vein endothelial cells, were stimulated by the addition of
      thrombin. Hirudin was added before thrombin in some experiments, and in other
      experiments the endothelium was pretreated with 0.5 mM acetylsalicylic acid
      (ASA). The distribution of platelet-endothelial cell adhesion molecule (PECAM), P
      selectin, von Willebrand factor (vWf), fibrinogen (FG) and thrombospondin (TSP)
      was investigated on fixed material from the three experimental settings by using
      an immunogold electron-microscopic technique on frozen thin sections. Cells that
      had not been exposed to thrombin or any other type of stimulation were used as
      controls. PECAM was the only adhesion molecule detected on HeLa cells. It
      outlined the membrane on tumour cells that were not adherent to platelets in both
      basic and hirudin experiments. However, tumour cells in close proximity to
      activated platelets were unlabelled. In contrast, PECAM was detected on both
      platelets and endothelium in all experimental settings and in controls. P
      selectin was only demonstrable on platelets in basic experiments. vWf was found
      both in endothelium and in platelets in controls and in all experimental
      settings. FG and TSP were found on platelets only, in a manner similar to that
      seen with vWf. Thus, among the adhesive factors examined in our experimental
      model, PECAM is the only one demonstrated on HeLa cells. This suggests that PECAM
      on tumour cells may play a role as adhesion molecule in the early stage of
      metastasis. P-selectin, vWf, FG and TSP were also consistently expressed.
      Therefore, these factors may contribute to the adhesive reactions involved in
      early metastasis.

PMID- 9269303
TI  - Microbiology of semen specimens from males attending a fertility clinic.
AB  - The relationship between semen quality, pyospermia and bacteriology was studied
      in 201 semen specimens from male patients attending a fertility clinic. Semen
      quality parameters were within normal limits in 115 (57%) patients, slightly
      reduced in 60 (30%), and 26 (13%) had findings indicating reduced fertility.
      Twelve patients (6%) had pyospermia. In 182 patients, 552 microorganisms were
      detected, including Enterobacteriaceae (2.8%), Gardnerella vaginalis (9.6%),
      Chlamydia trachomatis (1.6%), Mycoplasma genitalium (0.9%), and Ureaplasma
      urealyticum (11.8%). Semen quality was neither related to occurrence of
      microorganisms nor pyospermia. However, pyospermia was associated with
      simultaneous growth of Gardnerella vaginalis and Ureaplasma urealyticum. The
      exact nature of this association could not be ascertained, in as far as the males
      were not questioned about urethritis symptoms.

PMID- 9269304
TI  - Three-dimensional estimation of the glandular volume, and of the number and
      volume of epithelial cells in two glands from the antral mucosa of five healthy
      volunteers.
AB  - Specimens of antral mucosa were taken from five healthy volunteers and processed
      for microscopic evaluation. Consecutive 50-micron-thick sections were cut to
      estimate the volume of two antral glands. Two glands in each section were
      followed throughout by projecting their profiles from two microscopes mounted in
      parallel. The glandular volume was estimated using Cavalieri's principle. The
      mean volume of epithelial cells was estimated by systematic random sampling of
      the sections with an optical disector of known sample volume. The total number of
      cells per gland was calculated after determination of the volume of the glands
      and the mean volume of the epithelial cells. The mean volume of the antral glands
      was 13.6 +/- 1.67.10(6) microns3, whilst the mean volume of the epithelial cells
      was 1256 +/- 240 microns3. The total number of epithelial cells per gland was
      11216 +/- 1104. In conclusion, using stereological methods, the total number of
      cells as well as the cell volume and the volume of antral glands can be
      determined in routine biopsy specimens of human stomach provided that the total
      depth of the mucosa is present in the section.

PMID- 9269305
TI  - Current topics: radiosensitive human cells at the crossroads, high split-dose
      recovery and diminished inducible response.

PMID- 9269306
TI  - Differential involvement of chromosomes 1 and 4 in the formation of chromosomal
      aberrations in human lymphocytes after X-irradiation.
AB  - Whole blood samples from two healthy donors were cultured in the presence of 5
      bromo-2'-deoxyuridine (BrdU) for a total of 107 h following in vitro X
      irradiation with a dose of 2 Gy. Starting from 35 h after culture initiation,
      every subsequent 12 h a sample was taken from each culture and grown in the
      presence of demecolcine for another 12 h. At each sampling time, the aberrations
      involving chromosomes 1 and 4 were analysed using dual-colour fluorescence in
      situ hybridization (FISH) with chromosome-specific DNA libraries. Following
      differential staining of sister chromatids, the analysed cells were identified to
      be either in their first, second or third etc. mitosis after irradiation. Cells
      within the same postirradiation division contained higher frequencies of
      aberrations when derived from later sampling times, indicating a delay in
      progression of aberrant cells to mitosis. In contrast, when the aberration
      frequencies are calculated by sampling time (i.e. independent of the cell cycle)
      minimal effect of sampling time could be seen. This observation held true for all
      types of chromosomal aberrations. Analysis of about 2250 first-division cells for
      each donor (derived from all sampling times) indicates a relative
      overrepresentation of chromosome 4 in the formation of exchange
      aberrations/colour junctions. Whereas dicentric frequencies for chromosomes 1 and
      4 were close to the expected values based on the DNA content of these
      chromosomes, frequencies of reciprocal translocations showed a clear
      overinvolvement of chromosome 4. This resulted in a distinct difference in the
      reciprocal translocation to dicentric ratio, being 1.12 for chromosome 1 and 2.09
      for chromosome 4. These results indicate a non-DNA-proportional distribution of
      radiation-induced chromosome rearrangements in cultured human lymphocytes.

PMID- 9269307
TI  - Sequence-dependent variations of DNA structure modulate radiation-induced strand
      breakage.
AB  - Using a 80 base pair DNA fragment, the sequence-dependence was compared for: (i)
      the probability of fast neutrons induced strand breakage, (ii) the accessibility
      of the H4'- and H5'-atoms to OH. attack, (iii) the width of the minor groove, and
      (iv) the probability of OH. reactions with H4'- or H5'-atoms. The probability of
      strand breakage was measured using sequencing gel electrophoresis. The
      accessibility and the probability of reaction were calculated for the energy
      minimized modelled DNA fragment. A Monte-Carlo simulation was used for
      calculating the probabilities of H-atom abstraction by OH.. It was observed that
      reduced breakage occurs in sequences exhibiting low accessibility of H4' and H5'2
      and low probability of H-atom abstraction by OH., due to a narrow, minor groove.
      This shows that the breakage probability at a given nucleotide site is not
      determined by the chemical nature of the nucleotide (A, T, G or C), but mainly by
      the local sequence-modulated intrinsic structure. Fitting the experimental
      results with the calculated probabilities of reaction suggests that a C4'
      centered radical evolves towards a strand break three times more efficiently than
      the C5' one, and that half of the breaks occur via the 4'-path and half via the
      5'-path.

PMID- 9269308
TI  - Enhanced radiosensitivity by inhibition of nuclear factor kappa B activation in
      human malignant glioma cells.
AB  - To clarify the relationship between cellular radiosensitivity and nuclear factor
      kappa B (NF-kappa B) activation, an expression plasmid was constructed for I
      kappa B-alpha, a cellular inhibitory protein of NF-kappa B, and transfected it
      into two human malignant glioma cell lines. Cells overexpressing the I kappa B
      alpha protein were more radiosensitive than the parental cells and one
      transfected clone with low expression. In the parental cell lines and one
      transfected clone with low expression, the sequence specific DNA-binding activity
      of NF-kappa B was considerably increased between 1 and 2 h after irradiation. In
      contrast, no increase in the DNA-binding activity was observed in the transfected
      clone overexpressing I kappa B-alpha protein. These results suggest that the
      activation of NF-kappa B may be one of the intrinsic responses determining
      cellular radiosensitivity.

PMID- 9269309
TI  - The oxygen effect in permeabilized and histone-depleted cells: an enhanced OER
      for DNA double-strand breaks, compared to single-strand breaks, is abolished by
      soluble scavengers.
AB  - The oxygen enhancement ratios (OER) in mammalian cells for DNA single- and double
      strand breaks (ssb and dsb) are similar, usually 2-3. This seems to contradict
      the hypothesis that dsb are formed by multiple lesions, since one would then
      expect a quadratic OER for dsb compared to ssb. A higher OER for dsb than for ssb
      was however found in permeabilized cells (OERdsb = 7.7; OERssb = 4.3) and histone
      depleted cells (OERdsb = 20; OERssb = 2.3), in the presence of an SH-compound,
      mercaptoethylamine. This higher OER could be counteracted by addition of the OH
      radical scavenger DMSO. The OERdsb/OERssb ratio thus increases when the indirect
      effects increase. The repair of directly induced DNA lesions by hydrogen donation
      seems to be less efficient than the repair of indirectly induced lesions. It is
      suggested that differences in the fraction of unrepairable breaks differs for ssb
      and dsb and that this is the reason for the non-quadratic OERdsb compared to
      OERssb found in cells. In the absence of SH-compounds, there was no oxygen effect
      for ssb in permeabilized and histone-depleted cells. In contrast to this, a small
      oxygen effect was observed for dsb in permeabilized cells and this effect
      increased after histone depletion, reaching a value of OER = 1.8. This oxygen
      effect seems to be linked to generation of dsb by single OH radicals.

PMID- 9269311
TI  - Chromosome 2 hypersensitivity and clonal development in murine radiation acute
      myeloid leukaemia.
AB  - Acute myeloid leukaemias induced by ionizing radiation in mouse are characterized
      by chromosome (chr) 2 aberrations. While it is known that chr 2 aberrations form
      early and in abundance post-irradiation, unequivocal evidence for
      hypersensitivity of chr 2 in the first post-irradiation mitoses is lacking. Here
      it is established that chromosomal aberrations detected in bone marrow cells by
      chromosome painting are induced in all mice at an approximately 2-fold greater
      frequency in chr 2 by comparison with chrs 1 and 3 at 24 and 48 h following in
      vivo whole-body X-irradiation. Long-term follow up studies (to 15 months post
      irradiation) indicated that chromosomal hypersensitivity is accounted for largely
      by the existence of hot-spots for aberration formation on sensitive chromosomes.
      Analysis of clonal developments suggested that chr 2 aberrant clones are selected
      for entry into the proliferating bone marrow cell compartment in preference to
      cells with other aberrations and that these clones in general have a higher
      proliferative potential. However, neither the induction of chr 2 aberrations nor
      the presence of a chr 2 aberrant clone specifically predict the development of
      AML in an individual irradiated mouse. Nonetheless these events or sub-groups of
      these events are necessary for AML development.

PMID- 9269310
TI  - Heat effects on the repair of DNA double-strand breaks in CHO cells.
AB  - The effect of heat (43-45 degrees C) on the induction and the repair of DNA
      double-strand breaks (dsb) was studied in CHO cells after 60 Gy of X-rays using
      constant-field gel electrophoresis. Heat given prior to irradiation was found not
      to alter the number of dsb when measured immediately after irradiation. In non
      heated cells, about 80% of all dsb were rapidly repaired with a half-time of 4
      min, while 20% were repaired more slowly with T4 = 160 min. These kinetics were
      grossly altered by heat. Both the fast and the slow process were retarded.
      However, the main effect of heat was an increase in the number of slowly rejoined
      dsb. This increase was shown to result from the additional formation (up to 1.4
      fold the initial number) of dsb early during the repair course. It is suggested
      that the additional dsb arose from base damage, the repair of which was
      unbalanced by heat. No evidence was found for apoptosis being involved in this
      process. The kinetics of the additional dsb was found to correlate with thermal
      radiosensitization.

PMID- 9269312
TI  - Limiting dilution analysis of T-cell progenitors in the bone marrow of thymic
      lymphoma-susceptible B10 and -resistant C3H mice after fractionated whole-body X
      irradiation.
AB  - Earlier studies from this laboratory using Thy 1 congenic B10 strain mice
      suggested that a depletion of T cell progenitors (pre T cells) in the bone marrow
      in addition to the destruction of the thymus after fractionated whole body X
      irradiation (IR) are the two main critical factors that cause differentiation
      arrest of initially repopulating intrathymic radio-resistant T cell progenitors,
      which then lead to the appearance of preneoplastic, prelymphoma cells, and
      eventually to highly neoplastic thymic lymphomas under the influence of the
      thymic environment. In order to explore the significance of the depletion (or
      reduction) of T cell progenitors in the bone marrow during pathogenesis of
      radiation-induced thymic lymphomas, we compared the pool size of pre T cells in
      the bone marrow and the spleens as well as the profiles of the regenerating
      thymocyte populations between thymic lymphoma induction-susceptible B10 and 
      resistant C3H strain mice following irradiation. The results indicated that
      irradiation severely depleted the pre T cells in the bone marrow and the spleens
      of both lymphoma induction-susceptible and -resistant mice. They also showed that
      in C3H mice the differentiation and maturation of intrathymic T cell progenitors
      which initially repopulated the depleted thymus seemed to proceed normally in
      spite of the poor cellularity, while this process was greatly suppressed in B10
      mice. These data indicate that a depletion of pre T cells in the bone marrow
      combined with atrophy of the thymus in the irradiated mice is necessary, but not
      sufficient for development of thymic lymphoma. Implication of these findings on
      the possible mechanism of radiation-induced thymic lymphomagenesis is discussed.

PMID- 9269313
TI  - Late and persistent up-regulation of intercellular adhesion molecule-1 (ICAM-1)
      expression by ionizing radiation in human endothelial cells in vitro.
AB  - Adhesion molecules play a key role in cellular traffic through vascular
      endothelium, in particular during the inflammatory response when leukocytes
      migrate from blood into tissues. Since inflammation is one of the major
      consequences of radiation injury, we investigated the effect of ionizing
      radiation on cell-surface expression of the intercellular adhesion molecule-1
      (ICAM-1), the vascular cell adhesion molecule-1 (VCAM-1) and E-selectin in
      cultured human umbilical vein endothelial cells (HUVEC). Flow cytometry performed
      on irradiated HUVEC revealed both a time- (from 2 to 10 days) and dose- (from 2
      to 10 Gy) dependent up-regulation of basal expression of ICAM-1, and no induction
      of VCAM-1 or E-selectin. The radiation-induced increase in ICAM-1 expression on
      HUVEC was correlated with augmented adhesion of neutrophils on irradiated
      endothelial cells. Interleukin-6 (Il-6) or other soluble factors released by
      irradiation were not involved in the enhanced ICAM-1 expression by irradiation.
      Northern blot analysis showed an overexpression of ICAM-1 mRNA from 1 to 6 days
      after a 10 Gy exposure. Our data suggest that ICAM-1 participates in the
      radiation-induced inflammatory reaction of the endothelium.

PMID- 9269314
TI  - Modulation of radiation response of human tumour cells by the differentiation
      inducers, phenylacetate and phenylbutyrate.
AB  - The aromatic fatty acids phenylacetate (PA) and phenylbutyrate (PB) are novel
      antitumour agents currently under clinical evaluation. Their ability to induce
      tumour differentiation in laboratory models and their low clinical toxicity
      profile makes them promising candidates for combination with conventional
      therapies. In the present studies, we characterized the interactions between
      these aromatic fatty acids and radiation, using as a model cell lines derived
      from cancers of the prostate, breast, brain and colon. Analysis of the radiation
      response of the tumour lines using the linear-quadratic model, demonstrated that
      cellular exposure to pharmacological, non-toxic concentrations of either PA or PB
      resulted in time-dependent and contrasting changes in radiation response. While
      drug pretreatment for 24 h reduced radiation sensitivity (significant alterations
      in both alpha and beta parameters), pre treatment for 72 h significantly
      increased radiosensitivity (significant alterations in alpha and beta
      parameters). In replicating tumour cells, these changes were accompanied by a
      gradual G1-phase arrest. Cytostasis alone, however, could not explain
      radiosensitization, as similar alterations in radiation response were documented
      also in non-cycling cells. Modulation of tumour radiobiology by PA and PB was
      tightly correlated with early rise followed by decline in intracellular
      glutathione levels and the activity of antioxidant enzymes such as catalase,
      superoxide dismutase, glutathione reductase, glutathione peroxidase and
      glutathione S-transferase. Although in vitro findings identify the aromatic fatty
      acids PA and PB as a new class of non-toxic modulators of radiation response, the
      antagonistic effect of these compounds on radiation response needs further
      examination. Our data strongly suggest that for PA or PB to have a role in
      clinical radiotherapy, appropriate scheduling of combination therapies must take
      into account their time-dependent effects in order to achieve clinical
      radiosensitization.

PMID- 9269315
TI  - Exposure to ionizing radiation increases responsiveness to neural secretory
      stimuli in the ferret jejunum in vitro.
AB  - Experiments were designed to determine the effects of ionizing radiation on
      jejunal epithelial function in the ferret in vitro. Basal and stimulated
      electrolyte transport were determined in Ussing chambers at 0.5, 2, 24 and 48 h
      post-irradiation. Tissue histamine and 5-hydroxytryptamine levels were measured.
      Myeloperoxidase activity was also measured as an index of inflammation. Basal
      short circuit current was reduced at 2 h post-irradiation, but was elevated at 48
      h. Basal conductance was significantly increased by 24 and 48 h. Responsiveness
      to electrical field stimulation was depressed at 0.5 h, and was greater than
      control by 24 and 48 h post-irradiation. Similarly, short circuit current
      responses to prostaglandin E2 were depressed at 0.5 h and elevated at 24 h. No
      significant change was observed in the response to carbachol post-irradiation,
      indicating that alterations in responsiveness were not likely at the level of the
      enterocyte. Changes in responsiveness to electrical field stimulation correlated
      significantly with increases in mucosal mast cell numbers. Myeloperoxidase
      activity, indicative of neutrophil infiltration, did not increase post
      irradiation, nor was there histological evidence of an inflammatory cell
      infiltrate. There were no changes in tissue histamine or 5-hydroxytryptamine.
      Histology also revealed little microscopic morphological change from shams in
      tissue from irradiated ferrets. The results of this study demonstrate effects of
      irradiation on electrolyte transport in the ferret jejunum. The enhanced neurally
      evoked electrolyte transport observed at 24-48 h post-irradiation was not
      correlated with the development of inflammation, but was correlated with changes
      in mast cell numbers.

PMID- 9269316
TI  - Annexin I in fibrotic rat lung and cultured lung fibroblasts following
      irradiation.
AB  - Radiation-induced lung fibrosis is a result of collagen accumulation in the
      interstitium, partly due to increased collagen synthesis by fibroblasts. One
      feature of active collagen synthesis is increased membrane trafficking in the
      fibroblasts. A group of proteins called annexins is believed to play a regulatory
      role in membrane fusion and exocytosis. Therefore, increased annexin activity
      might be expected in the fibrotic lung. We tested this hypothesis by measuring
      annexin I levels, hydroxyproline content and ultrastructural changes in radiation
      induced pulmonary fibrosis in rat. Three months after a single exposure to 30 Gy
      of X-rays to the right hemithorax, the right lung of the rat was atrophied and
      fibrotic with a concomitant increase in size of the shielded left lung. Electron
      micrographs revealed that the irradiated lung was ladened with interstitial
      collagen fibrils, with increased number of fibroblasts amongst them.
      Hydroxyproline concentration in the irradiated lung was nearly twice that in the
      sham-irradiated lung. Annexin I in the irradiated lung, on the other hand, was
      markedly reduced, and barely detectable on immunoblots. Since increased annexin I
      might precede enhanced collagen production, we also measured annexin I levels in
      rat lungs 3 days after 30 Gy irradiation and correlated that with hydroxyproline
      concentration. We found no appreciable difference in annexin I levels and
      hydroxyproline content between sham-irradiated and irradiated lungs at 3 days. To
      determine whether annexin I levels in cultured fibroblasts were altered by
      irradiation, we assayed annexin I in cultured rat lung fibroblasts 3 days after
      0.10 Gy exposure, with concomitant measurement of 14C-proline incorporation. The
      annexin I level in fibroblasts irradiated with 10 Gy X-rays was 55% higher than
      in sham-irradiated fibroblasts. However, incorporation of 14C-proline into
      collagenase-sensitive macromolecules in the culture medium and extracellular
      matrix was not different between these two groups of cells. These data
      demonstrate a radiation-induced increase in immunoreactive annexin I in cultured
      lung fibroblasts, but fail to support the hypothesis of a positive correlation
      between annexin I concentration and fibrosis in irradiated rat lung.

PMID- 9269317
TI  - Biokinetics and dosimetry of chromium, cobalt, hydrogen, iron and zinc
      radionuclides in male reproductive tissues of the rat.
AB  - Following intravenous administration to male rats, the uptake and retention by
      reproductive tissues of chromium-51, cobalt-57, iron-59, zinc-65 and tritium has
      been studied for up to 28 days. Chromium-51, 57Co, 59Fe and 3H were not or only
      transiently accumulated in gonads or accessory sex glands at concentrations
      greater than whole body concentrations. However, 65Zn was concentrated in the
      dorsolateral region of the prostate gland and autoradiography showed preferential
      uptake by epithelial cells and lumen of glands. When combined with other
      information available from the literature, this data would suggest that current
      models adequately describe the biokinetics of chromium, cobalt, iron and tritium
      in the prostate and testes and zinc in the testes. Uptake of zinc by the prostate
      would appear to be best described by an average value of 0.1% and a conservative
      value of 0.5%. Allowing for greater uptake of zinc (0.5%) by the prostate, after
      inhalation of 65Zn in a soluble form increases prostate dose by about 3 fold
      compared to current models. The pessimistic assumptions of a higher relative
      biological effectiveness (20) for all Auger emissions from 65Zn in cell nuclei
      and a heterogeneous distribution of 65Zn to sensitive cells in the prostate
      increases prostate dose by a further factor of 9. Even on the basis of these
      cautions estimates, occupational exposures to radioisotopes of these elements do
      not explain the excess of prostate cancer reported amongst some nuclear workers.

PMID- 9269318
TI  - The effect of 50 Hz electromagnetic fields on the formation of micronuclei in
      rodent cell lines exposed to gamma radiation.
AB  - Low frequency electromagnetic fields (EMF) do not produce enough energy to damage
      DNA, in contrast to ionizing radiations. Any relationship between increased
      incidence of cancer and EMF must therefore be explained by a promoting effect on
      cellular transformation by ionizing radiation. The aim of this study was to
      investigate using the cytokinesis-blocked micronucleus assay a possible
      amplification of the genotoxic effects of ionizing radiations in cells exposed to
      combined static and power-frequency electromagnetic fields. Rat tracheal
      epithelial cell lines were first exposed in vitro to 60Co gamma rays (0, 2 and 6
      Gy) and cells were then cultured for 24 h in a homogeneous sinusoidal 50 Hz
      magnetic field (flux density: 100 microTrms) combined with an artificial
      geomagnetic-like field created by the use of horizontal and vertical pairs of
      Helmholtz coils. Control cells were cultured in an adjacent incubator where the
      background EMF was about 0.1 microTrms. Under our in vitro experimental
      conditions, EMF appeared to have no significant direct effect on micronucleus
      induction in rat tracheal cell lines. However, an increased frequency of
      binucleated cells with micronuclei was observed in cells exposed to 6 Gy of gamma
      rays and EMF, compared with gamma irradiation alone. This could enhance radiation
      induced genomic alterations and increase the probability of neoplastic
      transformation.

PMID- 9269319
TI  - Relationships between smoking habits, smoking-associated hematological changes,
      and urinary benzene metabolites.
AB  - It has been suggested that benzene metabolites might be good indicators of
      smoking. Moreover, benzene could stimulate the neutrophil lineage while
      depressing the lymphocytic and erythroid lineages, possibly by an interference
      with cytokines. The effect on the neutrophil lineage could explain the smokers'
      leukocytosis, the mechanism of which is presently unknown. Therefore, the
      usefulness of benzene metabolites as indicators of smoking was compared to that
      of cotinine and thiocyanate, and the relationships between benzene metabolites,
      the hematological parameters of smokers, and interleukin 1 alpha production were
      examined. The results show that benzene metabolites are not better indicators of
      smoking status than cotinine or thiocyanate. Furthermore, it seems unlikely that
      the smokers' leukocytosis is benzene induced.

PMID- 9269320
TI  - Epidemiologic assessment of measures used to indicate low-level exposure to
      mercury vapor (Hg).
AB  - Mercury (Hg) concentrations in individual spot urine samples collected over
      consecutive 1-d periods were compared with Hg concentrations measured in combined
      24-h urine samples from 69 practicing dental professionals with low exposure to
      Hg vapor (Hg) in order to validate the use of spot urine samples as an indicator
      of Hg exposure. The level of Hg in air as an exposure measure was also evaluated
      by comparing air concentrations of Hg in dental offices with both spot and 24-h
      urine Hg levels. The results showed: (1) There was little diurnal variation
      (approximately 9%) in urinary Hg values; (2) a strong correlation (R2 = .85)
      exists between the Hg concentration in the first morning void and that in a
      complete 24-h urine sample; (3) adjustment of urinary Hg levels for creatinine
      concentrations did not improve this correlation; (4) there was no added value in
      the speciation of total urinary Hg into the inorganic Hg fraction; and (5)
      concentrations of Hg in air did not significantly correlate with measures of Hg
      in urine at this low Hg exposure level. We conclude from this study that first
      morning void urine samples may be used to derive reasonably valid estimates of Hg
      concentrations found in the total amount of urine collected over a 24-h period.
      Thus, due to its comparability, ease of collection, and lower cost, the first
      morning urine void may be used in place of a sample collected over a full 24 h to
      facilitate Hg exposure assessments in epidemiologic studies that use urinary Hg
      levels as a measure of low-level Hg exposure.

PMID- 9269321
TI  - Mutagenicity of scooter exhaust particulate matter.
AB  - By using the in vitro Ames Salmonella/microsomal assay and the in vivo mouse
      micronucleus assay, studies were performed to evaluate the genotoxicity of
      gasoline exhaust particulate matter generated from five different domestic and
      imported scooters. In the Ames assay, treatment of test strains TA98 and TA100
      with solvent extracts of particulate matter from four of five scooter models
      caused an increase in the number of histidine-independent colonies over the
      background in TA98 without S9 mix. Positive results were also obtained from the
      micronucleus assay. The frequencies of bone marrow micronucleated polychromatic
      erythrocytes were significantly higher in the treated compared to the nontreated
      animals, and the increases in the frequencies were not significantly different
      among the five types of scooters. Analyses of chemical components showed that
      scooter exhaust particulate matter contained more than 100 different substances
      including polycyclic aromatic hydrocarbons.

PMID- 9269322
TI  - Differential carcinogenicity of benzo[a]pyrene in male and female CD-1 mouse
      lung.
AB  - Benzo[a]pyrene (BaP) is known to induce tumors in lung, forestomach, and skin in
      experimental animals. Earlier studies have suggested that glutathione S
      transferase pi (GST pi) is involved in the detoxification of the "ultimate"
      carcinogenic metabolite of BaP, 7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-oxy
      7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE). The constitutive expression of GST pi
      in the liver of the male CD-1 mouse is higher than that of the female, and BHA
      has been shown to preferentially induce GST pi in the female as compared with the
      male mouse. The present studies were therefore designed to compare the
      susceptibility of male and female CD-1 mice to the carcinogenic effects of BaP
      and the protective effect of BHA. Results of these studies show that the female
      CD-1 mice are more susceptibile to the carcinogenic effect of BaP than the males
      and that the attenuation of BaP-induced carcinogenesis by BHA appears to be
      restricted only to the females.

PMID- 9269323
TI  - Styrene-induced alterations in the respiratory tract of rats treated by
      inhalation or intraperitoneally.
AB  - Although exposure to styrene occurs primarily via inhalation, the action of this
      agent on the respiratory tract has scarcely been investigated. This article
      describes morphological and biochemical changes occurring in the respiratory
      tract of rats after either inhalation of styrene vapors (300 ppm, 6 h/d, 5 d/wk,
      for 2 wk) or systemic (ip) treatment with 40 or 400 mg/kg styrene for 3
      consecutive days. Electron microscopy analysis showed diffuse cell damage
      involving the tracheal, bronchiolar, and alveolar epithelium. In the tracheal
      epithelium, several cell types were affected. Ciliated cells presented
      vacuolation, detachment of cilia, blebbing of the apical cytoplasm, and compound
      cilia. Most secretory cells showed scant secretory granules and blebbings. Dense
      bodies and fibrillary inclusions were seen in intermediate and basal cells.
      Styrene also caused alterations of cytoplasmic components in type II pneumocytes
      and bronchiolar cells as well as thickness of the alveolar wall. These
      abnormalities were accompanied by depletion of glutathione (GSH) in the lung
      tissue. Pneumotoxic effects of systemic administration of styrene were dose
      dependent and tended to be more severe than those seen in the animals exposed for
      longer periods to styrene by inhalation. Metabolic activation of styrene and
      subsequent cell damage induced by the reactive metabolite styrene oxide may be
      involved in the sequence of events culminating in the toxic insult to the
      respiratory tract.

PMID- 9269325
TI  - Towards a validation of the micronucleus test.

PMID- 9269324
TI  - Developmental toxicity of dermally applied crude oils in rats.
AB  - Two crude oils, differing in viscosity (V) and nitrogen (N) and sulfur (S)
      content, were evaluated for pre- and postnatal developmental toxicity. In Crude I
      (low V, low N, low S) studies, the material was applied neat to the clipped backs
      of pregnant rats at dose levels of 0, 125, 500, 1000 (postnatal only), and 2000
      (prenatal only) mg/kg. In Crude II (high V, high N, moderate S) studies, the oil
      was applied similarly but at dose levels of 0, 30, 125, and 500 mg/kg. Rats were
      exposed to the crude oils on gestation days (GD) 0-19; application sites were not
      covered. "Prenatal" rats were killed on GD 20. "Postnatal" rats were allowed to
      deliver naturally; surviving dams and litters were killed 3-4 wk postpartum. Both
      crude oils produced maternal and developmental toxicity. Adverse fetal effects
      included increased in utero death, decreased body weight, and reduced
      ossification of skeletal elements. Parturition was delayed in Crude II dams at
      500 mg/kg. The 4-d viability index was decreased in all Crude II-exposed groups.
      Pup body weights were decreased by each oil, but at the high dose only. Prenatal
      effects are probably related to polynuclear aromatic compounds (PAC) found in
      petroleum. The cause(s) of delayed parturition and postnatal toxicity have not
      been determined.

PMID- 9269326
TI  - Historical perspectives on the development of the in vitro micronucleus test: a
      personal view.

PMID- 9269327
TI  - The advantages and disadvantages of the cytokinesis-block micronucleus method.
AB  - There is current interest in adopting the micronucleus test instead of metaphase
      analysis of chromosomes to assess the in vitro genotoxic potential of chemical
      and physical agents. In this paper, the advantages and disadvantages of the
      cytokinesis-block micronucleus technique relative to metaphase analysis of
      chromosomes and the conventional micronucleus technique that does not distinguish
      between dividing and non-dividing cells are discussed. Furthermore, additional
      features, such as the measurement of non-disjunction, excision-repairable DNA
      lesions and HPRT variants and possibilities for further improving the application
      of the cytokinesis-block method are proposed.

PMID- 9269328
TI  - The in vitro micronucleus test: a multi-endpoint assay to detect simultaneously
      mitotic delay, apoptosis, chromosome breakage, chromosome loss and non
      disjunction.
AB  - Genotoxicity testing aims to detect a large range of genetic damage endpoints and
      evaluate such results in context of cell survival. The cytokinesis block
      micronucleus test offers the advantage to provide simultaneously information on
      both cell cycle progression and chromosome/genome mutations. Indeed, 1.
      frequencies of cytokinesis-blocked binucleated cells (and polynucleated) are good
      estimators of the mitotic rate; 2. frequencies of apoptotic figures in
      mononucleated and binucleated cells provide a measure for cell death before or
      after cell division; 3. combination of fluorescence in situ hybridization (FISH)
      for centromere/telomeres and micronucleus scoring allows discrimination between
      clastogenic and aneugenic events; 4. detection of FISH signals for chromosome
      specific sequences in both macronuclei and micronuclei, discriminates between
      aneuploidy due to chromosome non-disjunction or to chromosome loss. The
      cytokinesis block in vitro micronucleus test is thus a cytogenetic multi-test
      providing mechanistic information with a simple, rapid, objective, microscopical
      analysis.

PMID- 9269329
TI  - Comparative evaluation of the in vitro micronucleus test and the alkaline single
      cell gel electrophoresis assay for the detection of DNA damaging agents:
      genotoxic effects of cobalt powder, tungsten carbide and cobalt-tungsten carbide.
AB  - Although it is well known that micronuclei may arise from either DNA breakage
      leading to acentric chromosome fragments or from chromosome/chromatid lagging in
      anaphase, the ratio between the amount of DNA breakage induced and the frequency
      of micronuclei expressed in the following interphase is unclear. With the
      development of the alkaline single cell gel electrophoresis assay, which measures
      single strand and/or double strand breaks in a cell by cell approach, it is new
      possible to address this question at the cellular level. We therefore compared
      the genotoxic potential of pure cobalt powder (Co) and a cobalt-containing alloy,
      cobalt-tungsten carbide (WC-Co), involved in specific lung disorders, in parallel
      with the alkaline single cell gel electrophoresis (SCGE) assay (comet assay) and
      the cytokinesis-blocked micronucleus (MN) test, both carried out in vitro on
      isolated human leukocytes. The comet assay indicated that the WC-Co mixture
      produced a higher level of DNA damage than Co alone; WC alone was not able to
      induce a dose-dependent DNA breakage effect as was seen for Co and WC-Co. Results
      from the MN test confirmed these observations. It was clear that the clastogenic
      property of Co-containing dust is significantly enhanced when the Co metal is
      mixed with WC and suggested that their physicochemical characteristics may act as
      one of the important parameters responsible for the increased incidence of lung
      cancers observed in the population of hard metal workers. In agreement with data
      obtained in the same laboratory on liposoluble chemicals (PCBs and chlorinated
      aliphatic hydrocarbons) and from the literature, the results indicate that both
      the comet assay and the micronucleus test were able to detect differences in the
      genotoxic potential of the compounds studied. Although the micronucleus test
      seemed to be less sensitive to assess a synergistic DNA damaging potential of the
      mixture involved, it detects chromosomal aberrations (chromosome/genome
      mutations) and not just repairable DNA breakage or alkali-labile sites.
      Combination of the comet assay and the in vitro MN test might therefore be
      recommended for genotoxins to understand the mechanisms underlying mutagenicity
      and to assess the lowest efficient dose.

PMID- 9269330
TI  - Comparative evaluation of the in vitro micronucleus test and the in vitro
      chromosome aberration test: industrial experience.
AB  - Because of its rapidness, simplicity and potential for automation, the
      measurement of micronucleated cells in vivo is not only equivalent to the
      analysis of chromosome aberrations, but often even preferred within routine
      genotoxicity testing. In order to evaluate the correlation between the in vitro
      micronucleus assay (MNT) and the in vitro chromosome aberration test (CA), we
      collected data from four pharmaceutical companies obtained either in Chinese
      hamster cell lines (CHO-K5, CHO-K1, V79) or in human peripheral blood
      lymphocytes. Among the 57 compounds included in this comparison, 45 compounds
      gave rise to concordant results in both assays (26 compounds negative in both
      assays; 19 compounds positive in both assays). The high percentage of
      concordance, i.e. about 79% is very promising and can be even increased to about
      88% by omitting the 3 aneugenic compounds and 2 compounds inducing
      endoreduplicated chromosomes which were found positive only in the in vitro MNT.
      The results are remarkable in particular considering that most of the compounds
      evaluated are 'standard' pharmaceutical compounds and thus are at most weak
      inducers of chromosome damage. Our comparison strongly supports that the in vitro
      micronucleus test is a suitable alternative to the in vitro chromosome aberration
      assay. Moreover, the MNT has the potential of not only detecting clastogens but
      additionally aneuploidy inducing chemicals.

PMID- 9269331
TI  - Induction of micronuclei in Syrian hamster embryo cells: comparison to results in
      the SHE cell transformation assay for National Toxicology Program test chemicals.
AB  - Sixteen chemicals currently being tested in National Toxicology Program (NTP)
      carcinogenicity studies were evaluated in the Syrian hamster embryo (SHE) cell in
      vitro micronucleus assay. Results from these studies were compared to the results
      from the SHE cell transformation assay for the same chemicals The overall
      concordance between induction of micronuclei and transformation of SHE cells was
      56%, which is far lower that the 93% concordance between these two tests reported
      previously by Fritzenschaf et al. (1993; Mutation Res. 319, 47-53). The
      difference between our results appears to be due to differences in the types of
      chemicals in the two studies. Overall, there is good agreement between the SHE
      cell micronucleus and transformation assays for mutagenic chemicals, but, as our
      study highlights, the SHE cell transformation assay has the added utility of
      detecting nonmutagenic carcinogens. The utility of a multi-endpoint assessment in
      SHE cells for carcinogen screening is discussed.

PMID- 9269332
TI  - Influence of culture time on the frequency and contents of human lymphocyte
      micronuclei with and without cytochalasin B.
AB  - The effects of culture time (52, 64 and 76 h) and cytochalasin B (Cyt-B, 3
      micrograms/ml) on the frequency of micronuclei (MN) harbouring whole chromosomes
      and acentric fragments was investigated in purified lymphocyte cultures of five
      nonsmoking male donors aged 41-50 years. Centromere-positive (C+) MN were
      identified by fluorescence in situ hybridization, using an alphoid DNA oligomer
      probe (SO-alpha AllCen) hybridizing to all human centromeres. For each culture
      time, 2000 cells and 60 MN were scored per donor, both with and without Cyt-B,
      making a total of 60,000 cells and 1800 MN. The frequency of MN and the
      proportion of C+ MN were higher at 64 h and 76 h than at 52 h, irrespective of
      Cyt-B. The culture time-dependent increase in MN frequency was mainly due to C+
      MN which were about 1.5-times more frequent at 64 h and 72 h than at 52 h. The
      frequencies of C+ MN, expressed per 1000 nuclei, were similar with and without
      Cyt-B, although the prevalence of C+ MN was consistently about 10 percent units
      higher in the former type of culture. This effect was due to a decreased
      frequency of centromere-negative (C-) MN in the binucleate cells, possibly
      reflecting, e.g. increased inclusion of acentric chromosomal fragments within the
      main nuclei of such cells, enhanced expulsion of C- MN, or selection against
      binucleate cells carrying such MN. In conclusion, the present findings indicate
      that MN harbouring whole chromosomes become more frequent at long culture times
      with and without Cyt-B and that Cyt-B-induced binucleate cells show a reduced
      frequency of MN containing acentric fragments. Due to the high background of
      whole-chromosome-containing MN (mean C+ MN proportions ranged from 42.3% to
      62.7%), it may be recommended that centromeric fluorescence in situ hybridization
      is routinely applied when lymphocyte MN are used as a biomarker of human exposure
      to clastogens.

PMID- 9269333
TI  - A critical evaluation of centromeric labeling to distinguish micronuclei induced
      by chromosomal loss and breakage in vitro.
AB  - The in vitro micronucleus assay in conjunction with CREST-staining and
      fluorescence in situ hybridization (FISH) with centromere-specific DNA probes is
      being increasingly utilized for the detection of clastogenic and aneuploidy
      inducing agents. Although potentially powerful techniques, both methods have
      unique characteristics that can influence sample processing and the
      interpretation of results. In this article, the use of the CREST and the FISH
      modifications of the in vitro micronucleus assay have been used to characterize
      the origin of the micronuclei induced by cyclophosphamide, 4,4'-methylene-bis(2
      chloroaniline), 4-nitroquinoline N-oxide and ionizing radiation in metabolically
      competent MCL-5 cells or a derived cell line lacking metabolic activation. Using
      these results and our previous experiences with these techniques, a detailed
      comparison including the strengths and limitations of each technique as well as
      potential problems in performing each assay and in analyzing the data is
      discussed. In spite of their limitations, our results to date indicate that CREST
      staining as well as FISH with centromere-specific DNA probes can be used to
      accurately distinguish micronuclei formed from chromosome loss from those
      originating from chromosome breakage and that these techniques can be valuable
      complements to the in vitro micronucleus assay.

PMID- 9269334
TI  - Micronuclei, centromere-positive micronuclei and chromosome nondisjunction in
      cytokinesis blocked human lymphocytes following mitomycin C or vincristine
      treatment.
AB  - The influence of sampling time on the frequencies of micronuclei, centromere
      positive micronuclei and chromosome nondisjunction was investigated in
      binucleated lymphocytes following treatment with a known clastogen (mitomycin C)
      or an aneuploidy-inducing agent (vincristine sulfate). Cytochalasin B (6
      micrograms/ml) was added 44 h after mitogen stimulation and cultures were
      harvested 12, 28, 36 and 48 h thereafter. Micronucleated cells and micronuclei
      were significantly induced by the two treatments at all sampling times.
      Furthermore, in situ hybridization with an 'all centromeres' probe showed that
      vincristine-induced micronuclei were prevalently centromere-positive whereas in
      mitomycin C-treated cultures only a minor fraction of induced micronuclei
      contained the hybridization signals. Chromosome nondisjunction rates, as measured
      by in situ hybridization with chromosome 7- and 11-specific alphoid probes,
      significantly increased following vincristine treatment. Chromosome
      nondisjunction and total micronucleus frequencies were found to increase with
      time both in controls and in mutagen-treated cultures, whereas the percentage of
      centromere-positive micronuclei in the different treatments was not influenced by
      the sampling time. Our data suggest that even in the presence of 6 micrograms/ml
      cytochalasin B, the abnormal segregation of binucleated cells may contribute to
      the baseline level of micronuclei and influence the results obtained. The
      introduction of a short cytochalasin B treatment (between 12 and 28 h) in the
      cytokinesis-blocked micronucleus assay may avoid the cytochalasin B effect on
      micronucleus frequencies.

PMID- 9269335
TI  - Flow cytometric analysis of micronuclei in cell cultures and human lymphocytes:
      advantages and disadvantages.
AB  - Flow cytometric techniques are described to quantify micronucleus (MN) induction
      in cell cultures and human lymphocytes. The advantages and disadvantages of these
      techniques are discussed. Because a suspension of nuclei and MN has to be
      prepared for flow cytometric measurements, care has to be taken to avoid
      unspecific debris that can influence the results. Using additional flow
      cytometric parameters, most of the unspecific particles in the suspension can,
      however, be gated out. Apoptotic cells and apoptotic bodies can overlap the MN
      during measurement, it is, therefore, proposed not to use the technique if
      apoptosis is induced by the respective treatment. Advantages of the automated
      flow cytometric techniques are that results can be obtained in short time
      intervals, the frequency of MN and the DNA distribution of MN can be measured
      simultaneously and flow sorting can be used for a further analysis of MN using
      other techniques.

PMID- 9269336
TI  - The primary rat hepatocyte micronucleus assay: general features.
AB  - Recent advances in cell culture have allowed proliferation of primary rat
      hepatocytes enabling the analysis of different cytogenetic endpoints such as
      sister chromatid exchanges (SCE), chromosomal aberrations and micronuclei. The
      latter are of particular interest as preparation, staining and analysis is less
      time-consuming than the analysis of chromosomal aberrations and SCE what makes
      micronuclei an attractive short-term assay. This paper gives (1) a summary of the
      specific features of primary hepatocytes including ploidy, nuclearity and
      multipolar mitoses, (2) a summary of the culture conditions for proliferation and
      the proliferation kinetics, (3) an experimentally based interpretation of the
      comparatively high background levels of cells with micronuclei, and (4) an
      experiment-based discussion of approaches to circumvent the major disadvantage:
      the cytochalasin B method cannot be applied due to the high percentage of
      binucleated cells.

PMID- 9269337
TI  - Application of the in vitro rat hepatocyte micronucleus assay in genetic
      toxicology testing.
AB  - The investigation of micronuclei in mitogenic stimulated hepatocytes in vitro is
      a quite new area of research. Nevertheless, a relatively large database
      comprising more than 40 tested compounds of various classes has been generated up
      to now. This paper reviews the available data for the in vitro rat hepatocyte
      micronucleus assay, showing a sensitivity of this assay in identifying mutagens
      and genotoxic liver carcinogens of about 85%. Additionally, all of the tested non
      carcinogens gave negative results. The use of primary hepatocytes instead of
      permanently dividing mammalian cell lines for the investigation of micronucleus
      induction has several advantages. (1) The broad spectrum of metabolizing enzymes
      expressed in primary hepatocytes ensures an adequate activation of most
      xenobiotics. (2) No transfer of activated metabolites via the culture medium is
      necessary in this system, since the metabolizing cells are the target cells
      themselves. (3) Whilst in experiments with permanently dividing cells the use of
      S9-mix restricts the treatment period with the test compounds to 2-6 h in the
      hepatocyte micronucleus assay continuous treatment of up to 48 h is possible.
      Investigations with the pyrrolizidine alkaloids retrorsine, monocrotaline and
      isatidine, strong mutagens and liver carcinogens, clearly showed that at least
      for isatidine a prolonged exposure period is essential to detect its mutagenic
      potential. This compound gave positive results in rat hepatocytes but not in V79
      cells/S9-mix cultures. (4) The results obtained with the hepatocyte micronucleus
      assay are in good agreement with the genotoxic profiles of most of the compounds
      tested. Only three polycyclic aromatic hydrocarbons led to 'false-negative'
      results, since they strongly inhibited hepatocyte proliferation and thereby
      prevented micronucleus formation. (5) Hepatocytes are target cells of special
      interest when compounds are investigated which act specifically in the liver.
      Especially for hepatocarcinogens classified as non-genotoxins in standard
      genotoxicity tests or for chemicals showing DNA-repair induction in hepatocytes
      but no mutagenicity in standard tests, the hepatocyte micronucleus assay can
      contribute to clarify the situation. (6) The rat hepatocyte micronucleus assay
      can be performed easily and without great efforts in parallel to the in vitro
      hepatocyte DNA repair test (UDS-test), using the same hepatocyte batches. (7)
      Similar to the two versions of the UDS-test, the hepatocyte micronucleus assay
      can be performed following an in vivo-in vitro protocol. In order to further
      validate the hepatocyte micronucleus assay, as a next step controlled
      interlaboratory studies should be initiated.

PMID- 9269338
TI  - Analysis of DES-induced micronuclei in binucleated rat fibroblasts: comparison
      between FISH with a rat satellite I probe and immunocytochemical staining with
      CREST serum.
AB  - The usefulness of fluorescence in situ hybridization (FISH) with rat satellite I
      DNA was compared with immunocytochemical staining with CREST serum for the
      analysis of the content of micronuclei from primary rat fibroblasts. We analyzed
      micronuclei induced in vitro by the aneugenic compound diethylstilbestrol (DES)
      or the clastogenic compound mitomycin C (MMC). Since a centromeric probe was not
      available for the rat, we isolated rat satellite I DNA by PCR with primers
      designed on the basis of the known rat satellite I DNA sequence. The PCR products
      obtained as well as the cloned PCR products showed hybridization to the
      centromeric regions of a large number of chromosomes, but not of chromosome 1,
      19, 20, X and Y. Clone 18-5 was further analyzed and was shown to contain at
      least 4 repeats of the rat satellite I family. This probe, which hybridizes in
      the centromeric region of 34 of the 42 chromosomes, was used throughout the study
      as a probe for the FISH analysis of the micronuclei. For the immunocytochemical
      staining, the commonly used commercial anti-centromeric antibodies could not be
      used because of the weakness of the fluorescent signals given. Consequently,
      CREST serum of a single patient was used, which showed bright and distinct
      signals on the kinetochores of each chromosome. After treatment of the cells with
      the aneugen DES an increase in centromere (FISH) and kinetochore (CREST) positive
      micronuclei was found, whereas after treatment with the clastogen MMC, the
      percentage of centromere-positive micronuclei was similar to that observed in
      controls. Analysis of a large number of DES-induced micronuclei showed that the
      immunocytochemical method is equally as or slightly less sensitive for the
      detection of chromosomes in micronuclei and we therefore recommend FISH with
      probe 18-5 for the detection of chromosome loss in rat cells.

PMID- 9269339
TI  - Comparative induction of micronuclei in repair-deficient and -proficient Chinese
      hamster cell lines following clastogen or aneugen exposures.
AB  - The Chinese hamster cell line V79-4 and two ionising radiation-sensitive mutants
      irs1 and irs3, were used to assess the genotoxic effects of a clastogen (X-rays),
      an aneugen (podophyllotoxin) and an agent having both activities (etoposide),
      using the cytokinesis-block micronucleus assay combined with kinetochore
      labelling. All three agents induced micronuclei in a dose-dependent manner.
      Between 70 and 90% of the micronuclei induced by X-rays were kinetochore-negative
      and indicative of clastogenic activity, the relative frequencies of which were
      increased in the repair-deficient cell lines. In contrast, podophyllotoxin
      induced mainly kinetochore-positive micronuclei (up to 97%) and could be
      classified as an inducer of chromosome lagging and was essentially aneugenic in
      its activity. Micronuclei induced by etoposide were 61-84% kinetochore-negative
      and 26-39% kinetochore-positive, indicating both clastogenic and aneugenic
      activity. In the case of both etoposide and podophyllotoxin, there were no
      observed differences in the induction of micronuclei between the wild-type and
      repair-deficient cell lines. The data demonstrate the effectiveness of the
      cytokinesis-block micronucleus/kinetochore assay in determining the mechanisms of
      action of both chemicals and radiations upon chromosome structure and number and
      the potential influences of repair upon micronuclei induction.

PMID- 9269341
TI  - The position of the in vitro micronucleus test within the battery of screening
      for genotoxic potential determination and the regulatory guidelines.
AB  - The in vitro micronucleus test is available to demonstrate the clastogenic and
      aneugenic potencies of chemicals. This test is easier to evaluate than metaphase
      analysis and, although used routinely by some laboratories as a prescreening test
      for the determination of chromosomal mutation induction potency, it has not been
      recognised by regulatory authorities as a test to be included in the battery of
      assays for human risk assessment. This limitation is due to the lack of a fixed
      protocol, a limited data bank, particularly in the case of clastogens, and to the
      lack of sufficient robust interlaboratory validation studies. If we aim to
      recognize this test in the form of an OECD guideline and to introduce it as an
      alternative to in vitro metaphase analysis in cell culture, it is necessary to
      begin a collaborative study in order to determine the best protocol which is
      valid for the detection of all clastogens as well as to determine clearly the
      limits of the test. The use of this in vitro test as a prescreening assay could
      be very useful as it takes structural and numerical chromosomal abnormalities
      into account and is simpler to perform than in vitro metaphase analysis.

PMID- 9269340
TI  - Human lymphocytes micronucleus assay in Europe. An international survey.
AB  - The human lymphocytes micronucleus assay has been extensively used in Europe
      since the cytochalasin-B method was introduced. However, a large range of inter
      laboratory variability has been reported, limiting its applicability in European
      coordinated projects as well as its acceptance in international regulatory
      guidelines. Thus, an European survey was proposed in order to (a) determine the
      present state of the human lymphocytes micronuclei assay, (b) review
      methodological and scientific aspects, and (c) identify discrepancies in the
      criteria employed by different laboratories that could account for the lack of
      reproducible results. The outcome of the study with 30 European laboratories
      surveyed, reflects an immature state of the micronuclei assay in Europe, with (a)
      disparity in criteria and methodologies, (b) high diversity in the methods of
      statistical analyses employed, (c) non-uniform criteria for determining positive
      responses, and (d) a still rare use of new or emerging methodologies. The
      reported average baseline frequency of micronuclei in human lymphocytes was 7.8
      +/- 5.2 per 1000 cells (ranging from 3 to 23), with age and sex but not smoking
      as being main confounding factors. The general opinion was that more basic
      research on the micronucleus assay itself is required before considering this
      technique as an alternative to the chromosomal aberration assay, and that it is a
      suitable method to detect aneuploidy, mainly in vitro, and specially when coupled
      with molecular cytogenetic techniques.

PMID- 9269342
TI  - Detailed data on in vitro MNT and in vitro CA: industrial experience.

PMID- 9269343
TI  - Stress fracture of the second rib as a cause of back pain.

PMID- 9269344
TI  - Designer drugs--the Ecstasy and the agony.

PMID- 9269345
TI  - SMA Lecture. Impact of a free market system on medicine in Singapore. Singapore
      Medical Association.

PMID- 9269346
TI  - Endometrial hyperplasia and the risk of endometrial carcinoma.
AB  - OBJECTIVES: To determine the incidence of endometrial carcinoma in endometrial
      hyperplasia and try to identify those patients at greatest risk. METHODS: We
      conducted a retrospective study of 116 patients who had simple, complex or mixed
      (simple with focal complex) endometrial hyperplasia with or without atypia, from
      January 1991 to December 1994. RESULTS: Twenty-nine patients had endometrial
      hyperplasia with atypia and 87 without atypia. Incidence of endometrial carcinoma
      was 27.6% in those with atypia; and 3.4% in those without atypia. All were stage
      I (A or B) adenocarcinomas. Polycystic Ovary Disease and subfertility were found
      significantly in the cases with cytological atypia; however, they were not
      significant in the cases with carcinoma. No significant historical differences
      that could predict carcinoma were found.

PMID- 9269347
TI  - Clinical course and outcome of primary acute angle-closure glaucoma in Singapore.
AB  - PURPOSE: Data is lacking with regard to the factors which may predict the outcome
      of an acute glaucoma eye to treatment and its long-term prognosis. This study was
      carried out to identify such factors, in particular among Singaporeans. METHODS:
      Fifty-seven eyes were included in this retrospective analysis and factors
      analysed included age and sex; the duration of onset of symptoms to the time they
      presented to hospital; state of pupil and presenting intraocular pressure (IOP);
      whether attack is terminated by medical treatment alone or a second procedure (eg
      laser, trabeculectomy) was required; final outcome with respect to the
      development of chronic angle closure glaucoma and state of pupil at last follow
      up. RESULTS: Patients with 24 to 72 hours' delay in presentation had a relative
      risk of 2.78 (CI = 1.03-7.46) in developing chronic glaucoma. Those who required
      the addition of a laser procedure to control the initial presenting IOP while
      those who proceeded to a trabeculectomy had relative risks of 3.63 (CI = 1.49
      8.89) and 4.83 (CI = 1.18-19.7) respectively in developing chronic glaucoma when
      compared to patients who did not require any secondary treatment. CONCLUSION:
      Delay in presentation, and unresponsiveness to medical treatment in termination
      of the acute attack in an acute angle closure glaucoma patient carry a
      significant risk of chronic glaucoma.

PMID- 9269348
TI  - Inpatient group psychotherapy in Chinese patients.
AB  - OBJECTIVE: Inpatient group psychotherapy in acute psychiatric units has been a
      much maligned treatment modality with doubts cast upon its therapeutic value.
      However, local Chinese patients value and benefit from its inclusion in the
      therapeutic package after some adjustments to its structure and content. DESIGN:
      Groups of 8 inpatients met weekly with a regular therapist and co-therapist.
      Feedback forms were filled by consenting patients at the end of each session to
      rate the value of each treatment modality in the ward package and to ascertain if
      therapeutic factors had been achieved. SETTING AND PATIENTS: All were voluntary
      patients on an acute psychiatric ward based in a general hospital, who had
      consented to attend group therapy and were able to sit through a 45-minute
      session. Excluded were those with dementia, organic brain syndrome or those who
      were too disturbed. Thirty-nine patients completed the questionnaire legibly.
      RESULTS: In order of preference, patients rated individual attention from doctors
      first, followed by medication, relaxation therapy, then group therapy. Among the
      therapeutic factors, the ones achieved most were acceptance, altruism and self
      awareness. Patients wanted instruction and advice on mental health. Twenty-eight
      of thirty-nine patients wanted to continue attending group therapy. CONCLUSION:
      In this study, group therapy ranked 4th in the therapy package on an inpatient
      unit. Patients were able to experience some therapeutic factors but they valued
      factors which were different from those described in Western literature.
      Increased educational input from therapists was the preferred agenda.

PMID- 9269349
TI  - The results of open acromioplasty in impingement syndrome--a retrospective study.
AB  - Many published reports have reported generally good results of open acromioplasty
      in shoulder impingement syndrome. This paper studied retrospectively the results
      of open acromioplasty done in the Singapore General Hospital. A total of 23 open
      acromioplasties performed on 22 patients with shoulder impingement syndrome were
      studied. The post-operative results of the acromioplasties were evaluated using
      the University of California, Los Angeles (UCLA) shoulder scoring system. With
      the UCLA shoulder scoring system, results were excellent or good in 14 (60.8%),
      fair in 7 (30.5%) and poor in 2 (8.7%). At the same time the male sex was
      identified to have statistically significant better results as compared to the
      females. There was a trend towards poorer results in those at or above 50 years
      of age, duration of symptoms of less than 2 years and those with acromiohumeral
      distance of less than or equal to 1.0 cm. The presence of rotator cuff tears and
      the duration of follow-up were found not to have any bearing on the post
      operative outcome. This procedure seems to be reasonably effective and safe.
      Careful patient selection and early post-operative rehabilitation with
      physiotherapy is of utmost importance.

PMID- 9269350
TI  - Bone mineral density measurements using the Hologic QD2000 in 175 Singaporean
      women aged 20-80.
AB  - AIMS: The first aim is to obtain a reference database of bone mineral density
      (BMD) measurements for Singaporean women across different age groups and to
      compare this with an American database using the same machine. The second is to
      study the lifestyle factors that may influence bone mass in these women. METHODS:
      Subjects were recruited from hospital staff and their relatives. They needed to
      fulfil inclusion criteria and those with confounding factors such as being on
      hormone replacement therapy (HRT) were excluded. A lifestyle questionnaire was
      administered. RESULTS: Across every five-year age band, the mean BMD measurements
      of the Singaporean women were 3%-8% lower than their American counterparts at the
      AP spine and 6%-11% lower at the femoral neck. 40.6% either drank milk, ate
      cheese or took calcium supplements everyday. 16.6% did some form of weight
      bearing exercise at least once a week. CONCLUSION: A local reference database is
      needed for the accurate interpretation of BMD measurements as there is
      significant variation compared to Caucasian values.

PMID- 9269351
TI  - Cervical ectopic pregnancy--a case report.
AB  - Mdm LLG, a 28-year-old Chinese, a gravida 2 para I, presented at 9 weeks of
      pregnancy with painless vaginal bleeding. Ultrasound examination showed features
      of a cervical pregnancy. Hysterectomy was employed for treatment. Various recent
      conservative and surgical treatment modalities employed for this condition are
      discussed.

PMID- 9269353
TI  - CMV colitis masquerading as colon cancer--an unusual presentation of acquired
      immunodeficiency syndrome.
AB  - We present a case-report of a patient with a typical history and a barium enema
      study diagnostic of right-sided colonic cancer. Laparotomy and right
      hemicolectomy was carried out. Histological examination revealed Cytomegalovirus
      (CMV) colitis and the patient was subsequently tested positive for Human
      immunodeficiency Virus (HIV). Gastrointestinal symptoms are common in patients
      with Acquired Immune Deficiency Syndrome (AIDS) and up to 10% of all AIDS
      patients have CMV colitis. The diagnostic criteria for CMV colitis is reviewed.
      AIDS is likely to become more common and we stress the awareness of this
      condition as well as the need for preoperative colonoscopy and histological
      diagnosis in patients with radiological diagnosis of colorectal carcinoma.

PMID- 9269352
TI  - Ectopic Cushing's syndrome in a young female with atypical [corrected] bronchial
      carcinoid tumour.
AB  - A 17-year-old female with a large mass in the left thorax presenting with ectopic
      Cushing's syndrome is described. Biochemical evaluation revealed a
      corticotropin(ACTH)-dependent hypercortisol state. Surgical resection of the
      tumour resulted in clinical remission and correction of hypercortisolism and
      normal plasma ACTH levels. The histology was that of an atypical carcinoid.
      Bronchial carcinoid tumour is an extremely uncommon but well recognised cause of
      ectopic Cushing's syndrome. These patients may pose diagnostic dilemma in
      distinguishing form those with Cushing's disease because of the similarity in the
      clinical, biochemical and radiologic findings.

PMID- 9269354
TI  - Cardiac tamponade--an unlikely cause of unexplained hypotension in an isolated
      "minor" blunt chest injury.
AB  - Cardiac tamponade after a minor blunt chest trauma is indeed rare. Here, we
      report on one such case presenting with unexplained hypotension at the Emergency
      Department. The problems of diagnosis and treatment are discussed. In short, the
      proper management of this life-threatening condition can only be rendered by a
      high index of suspicion and close vigilance.

PMID- 9269355
TI  - Tendon xanthoma in familial hypercholesterolemia--a clinical and ultrasonographic
      study.
AB  - Familial hypercholesterolemia is a common autosomal dominant condition
      characterised by increased low density lipoprotein cholesterol, tendon xanthomas
      and premature atherosclerosis. Ultrasonography is the diagnostic tool of choice
      for the detection of tendon xanthomas in the Achilles tendon, demonstrated by the
      presence of hypoechoeic nodules or an increase in the antero-posterior diameter.
      It can also be used in screening and clinical follow-up of patients with familial
      hypercholesterolemia.

PMID- 9269356
TI  - Clinics in diagnostic imaging (21). Intraosseous lipoma of the calcaneum.
AB  - A 50-year-old woman presented with plantar foot pain. Radiographs and computed
      tomography demonstrated an intraosseous lipoma of the calcaneum. Curettage and
      packing were performed. The imaging features, including the magnetic resonance
      appearances, of intraosseous lipomas are described.

PMID- 9269357
TI  - What you need to know: addiction--Ecstasy.

PMID- 9269358
TI  - Discussion of an interesting case of Crohn's disease.
AB  - An interesting case of Crohn's disease is discussed whose initial presentation
      and diagnosis was that of irritable bowel syndrome. The key points in this case
      were the change in symptoms with time, the presence of alarm symptoms such as
      loss of weight, bleeding per rectum and tenesmus. The indication for further
      diagnostic investigations whether invasive or not is a lesson to learn.

PMID- 9269359
TI  - Smoking.

PMID- 9269360
TI  - Smoking in the Singapore Armed Forces.
AB  - The Singapore Armed Forces has, since 1986, established a comprehensive smoking
      control programme which combines health education, counselling and administrative
      measures aimed at discouraging non-smokers from smoking, and encouraging smokers
      to quit the habit. The prevalence of regular smoking decreased from 28.6% in 1987
      to 20.7% in 1993. The latest, 1993 survey as in past surveys covered 3,545
      respondents, made up of regulars (32.0%), NSF (62.2%) and NUSAF (5.6%). The 1993
      survey revealed that the majority of smokers (88.9%) in the SAF who consist
      primarily of 18 to 20-year-olds, had started smoking before enlistment. Most
      acquired the habit on their own (49.8%) or through influences outside the SAF
      (40.3%). Very few smokers became smokers through the influence of fellow soldiers
      (4.9%). The majority (87.7%) of smokers readily agreed that smoking is harmful,
      but this is not translated into practice. Health education efforts need to focus
      more on bringing about positive attitudinal and behavioural changes, rather than
      merely give information and advice. The young age of smoking onset (mean age of
      14.3 years) In the SAF population surveyed points to the need to focus preventive
      efforts further upstream than hitherto emphasised.

PMID- 9269361
TI  - Incidence of retinopathy of prematurity in Singapore.
AB  - The study was done to investigate the incidence and severity of retinopathy of
      prematurity (ROP) in Singapore over a one-year period. Its relation to factors
      like birth weight, gestational age are also explored so as to identify high risk
      groups and provide guidelines for the implementation of a screening programme in
      Singapore. At the various government restructured hospitals from Dec 1993 to Nov
      1994, 34.4% (72 out of 209) of babies, with birth weights less than 1250 g or
      gestational ages less than 32 weeks, developed ROP. The incidence of ROP
      correlated significantly with low birth weight, early gestational age, multiple
      births; the severity correlated with low birth weight and multiple births. There
      was a notably higher proportion of Malays in the study population (premature
      babies) than all the live births of the same period. From the results, an optimal
      screening programme should include babies weighing less than 1250 g or of
      gestation earlier than 32 weeks. A first examination at 33 weeks of post
      menstrual age is suggested.

PMID- 9269362
TI  - Plating of displaced mid-tibial fractures--a retrospective review of 80 cases.
AB  - We present a 2-year retrospective review and study of 80 patients admitted to our
      department with displaced mid-tibial fractures and treated by plate-fixation.
      This review paid particular attention to various complications that arose post
      operatively. The incidence of post-operative complications was 22.5%, with one
      death. The main complications were infections and refractures. Among those
      infected, there were no cases of osteomyelitis. We did not find a statistically
      significant difference in infection rates between the closed and open grades of
      fractures. We conclude that plate fixation of mid-tibial fractures is comparable
      with other modalities of treatment.

PMID- 9269363
TI  - Comparison of formalin preserved bone allograft in the form of a paste and as
      bone chips in fresh femoral shaft fractures with comminution.
AB  - Femoral shaft fractures with comminution are indicators for primary bone
      grafting. Problems related to autograft use have led us to evolve methods using
      allografts preserved in formalin. This method is cheap, easy, reliable and is
      readily available in the poorer countries. Comparison of 20 cases using allograft
      paste with 20 cases using allograft chips slivers in similar femoral shaft
      fractures was done. In both cases, the fusion time was slightly delayed as
      compared to cases using autograft. The infection rates were comparable, but it
      was noticed that bone paste got resorbed in 2 cases, leading to plate bending and
      malunion. The theoretical advantage of the bone paste in filling up the defects
      and crevices in the comminuted fractures was offset by the practical disadvantage
      of having no osteoconductive scaffolding, which was provided by the bone chips.
      It is thus recommended that formalin preserved bone allograft paste may be better
      suited for use in bony cavities and joint replacements, while formalin preserved
      bone chips are a good alternative to bone autografts, especially in polytrauma
      cases. Formalin preserved allografts are a viable alternative method for use in
      third world countries.

PMID- 9269364
TI  - Combination of suppository diclofenac and intravenous morphine infusion in post
      caesarean section pain relief--a step towards balanced analgesia?
AB  - Post-Caesarean section analgesia can be achieved by morphine infusion. NSAIDs are
      frequently administered to relieve uterine cramps. This study is aimed at
      assessing the efficacy of the combination of suppository diclofenac and morphine
      infusion in post-Caesarean section pain relief. General anaesthesia was given to
      60 patients who were randomly allocated into two groups: group A received 100 mg
      suppository diclofenac before surgical incision and morphine infusion 1.5 mg per
      hour postoperatively while group B received only morphine infusion 1.5 mg/H
      postoperatively. Pain assessment was done by an unbiased observer on arrival of
      the patients in the recovery room, then 6 hours, 12 hours and 24 hours later.
      Pain relief was found to be better in group A, with group B requiring more
      supplemental analgesia. Apart from better analgesic effect for wound pain, group
      A also had more favourable scores for uterine cramping pain. The incidence of
      nausea or vomiting was similar in both groups. No respiratory depression was
      observed in both groups. Two cases of increased bleeding (one from each group)
      were observed, both receiving conservative treatment. THE CONCLUSION: suppository
      diclofenac improved the analgesic efficacy of morphine infusion in post-Caesarean
      analgesia.

PMID- 9269365
TI  - The autopsy.
AB  - The autopsy can be divided into medico-legal and academic autopsies. The autopsy
      has proven its value in the elucidation of the cause of death, medical audit,
      clinical quality control, education and the continuing understanding of disease
      pathogenesis. In addition, the medico-legal autopsy plays an important role in
      the administration of justice. While the rate of medico-legal autopsies remains
      relatively stable, all over the world there has been a steady decline in the rate
      of academic autopsies. Most studies show an unsatisfactory agreement between the
      clinical diagnosis and the autopsy diagnosis. When the pattern of autopsies is
      skewed towards deaths of medico-legal significance, health statistics based on
      death certificates on which healthcare policies are formulated may not be useful.
      Therefore, the decline in autopsy rates should be reversed. All health
      professionals, hospital administrators, medical students and relatives should be
      educated about the relevance of the autopsy to each of them. There must be
      increased communication between the clinician and the pathologist.

PMID- 9269366
TI  - Spontaneous lumbar subdural haematoma--a case report.
AB  - Spinal subdural haematomas are a rare cause of spinal cord or cauda equina
      compression. These are usually seen in association with lumbar puncture or
      coagulopathy. Spontaneous spinal subdural haematomas are even rarer. This report
      presents one such case diagnosed by magnetic resonance imaging (MRI) together
      with a review of the literature. The patient presented with low back pain of
      acute onset after minimal trauma. MRI showed high signal intensity on both T1
      weighted and T2-weighted sequences in the posterior subdural space indicative of
      a subacute lumbar subdural haematoma. There was no history of bleeding
      diasthesis. The patient was treated conservatively and recovered spontaneously.

PMID- 9269367
TI  - Early closure of coronary cameral fistula in a 3.9 kg infant.
AB  - Congenital communications between the coronary artery and cardiac chambers are
      rare. The majority of cases present in adulthood. We report a patient with a
      coronary cameral fistula in which surgical closure of the fistula was performed
      at 10 weeks of age at a weight of 3.9 kg. We recommend early closure of coronary
      cameral fistula in symptomatic patients. Low weight or young age at presentation
      should not be a limiting factor.

PMID- 9269368
TI  - Real time ultrasound diagnosis of non-vaterian duodenal adenoma--a brief case
      report.
AB  - Non-vaterian duodenal adenomas are rare lesions, usually present with bleeding
      and abdominal pain. Sonography is often the first imaging procedure in patients
      with vague upper abdominal complaints, unsuspected duodenal pathology may be
      encountered. It is now widely accepted as the first choice for the investigation
      of abdominal masses. Oral water load is recognised as a good procedure for the
      detection of a bowel-related mass during sonographic examination. In our case, we
      used the real-time ultrasound with water ingestion to detect the location of the
      duodenal lesion and its relationship to the neighboring structure. This report
      demonstrates that conventional real-time ultrasound is still a simple method to
      diagnose duodenal lesions.

PMID- 9269369
TI  - Transient quadriceps paresis after ilioinguinal nerve block.

PMID- 9269370
TI  - Partial monosomy for chromosome 22 in a girl with mental retardation.
AB  - This report describes a 5-year 6-month-old Chinese girl with partial monosomy for
      the long arm of chromosome 22. The karyotype was 46,XX/46,XX,del (22) (q13.2).
      She presented with global developmental delay. Clinical features include
      seizures, failure-to-thrive, prominent ears, long philtrum and abnormal skin
      pigmentation on the face and limbs.

PMID- 9269371
TI  - Clinics in diagnostic imaging (22). Calcified peritoneal carcinomatosis.
AB  - A 37-year-old woman, with previously resected mucinous adenocarcinoma of the
      colon, presented with menorrhagia and a palpable pelvic mass. Radiographs and
      computed tomography (CT) demonstrated calcified peritoneal carcinomatosis in the
      abdomen and pelvis. Types of abdominal calcifications and imaging of
      intraperitoneal masses, particularly of peritoneal tumours, are discussed.

PMID- 9269372
TI  - What you need to know: addiction--prescribing naltrexone.
AB  - Naltrexone is of proven efficacy as a treatment modality in the relapse
      preventive programme of opiate abusers. It complements the other interventions
      such as individual counselling, family therapy and self-help groups. The
      initiation of naltrexone therapy after detoxification would be of vital
      importance in maintaining an individual's drug-free state. Naltrexone has no
      intrinsic opiate activity and has no resale value in the black market unlike
      methadone.

PMID- 9269373
TI  - Neonatal prediction of late neurodevelopmental deficits.

PMID- 9269374
TI  - Genetics of Alzheimer's disease: just how is molecular biology going to help
      grandma?

PMID- 9269375
TI  - Emergency department complaints: a ten-year review.
AB  - This 10-year (May 1986-31 December 1995) retrospective study was done to analyse
      the types of complaints received by the National University Hospital's Emergency
      Department (NUH EMD), so as to take remedial measures. It was done by reviewing
      three sources of complaints received by the department, namely formal written
      complaints, verbal feedback received by the Corporate Affairs Department, and via
      feedback forms. The areas of complaints looked for included the nature, number,
      validity, whether remediable and triage priority of the patients. One hundred and
      eighty-eight subcategories of complaints were received from 169 complaints. The
      complaint frequency was 0.26 per 1,000 visits or 1 complaint per 3,846 visits.
      The complaint frequency over the 10 years did not vary much (range 0 to 0.44).
      Most of the complaints are divided into 4 broad categories ie medical, doctor
      patient/paramedical staff-patient relationship, patient flow/logistics at EMD and
      in-house complaints. The majority (71.3%) of the complaints were due to medical
      and doctor-patient relationship problems. Complaints tend to arise from Priority
      2 and 3 rather than Priority 1 patients. 33.7% of the complaints were considered
      valid, 21.6% not valid while in the remaining 44.7%, validity could not be
      determined. 48.4% of complaints were likely to be remediable. Based on this
      study, we have since instituted a compulsory emergency department-driven
      "Customer Service Training Programme" and weekly teaching sessions for each
      incoming group of medical officers posted to the NUH EMD.

PMID- 9269376
TI  - Neurodevelopmental outcome of Malaysian very low birth weight infants: predictive
      value of cranial ultrasound appearances.
AB  - The aim of the study was to determine the predictive value of cranial ultrasound
      scans done in the neonatal period for neurodevelopmental outcome of the Malaysian
      very low birthweight (VLBW, < 1500 grams) infants assessed at 12 months of
      corrected age. Of the 101 infants studied, 68 (67.3%) were neurodevelopmentally
      normal at one year of age, 18 (17.8%) had major and 15 (14.9%) had minor
      neurodevelopmental impairment. Neurodevelopmental outcome was normal in 66/88
      (75.0%) infants who did not have severe intraventricular haemorrhage (IVH) or
      periventricular intraparenchymal echo densities (PVE) in the first week of life,
      and in 57/73 (78.1%) with uncomplicated scans at discharge. In contrast, 11/13
      (84.6%) with parenchymal echo densities or severe intraventricular bleed in the
      early neonatal period and 17/28 (60.7%) with complicated scans at discharge had
      adverse sequelae. There was a significant association between lesions seen on
      cranial ultrasound in the neonatal period and subsequent neurodevelopmental
      impairment. Late neonatal ultrasound scans appear to be a better predictor of
      short-term neurodevelopmental outcome than early scans.

PMID- 9269377
TI  - The NUH Memory Clinic. National University Hospital, Singapore.
AB  - OBJECTIVE: To assess the cognitive performance of elderly patients referred to
      the memory clinic. DESIGN: The patients were interviewed using the computerised
      mental state programme, GMS-AGECAT, and assessed on the Cognitive Assessment
      Scale (CAS) which includes the Elderly Cognitive Assessment Questionnaire (ECAQ)
      and the Cambridge Memory Test (CMT), modified for Chinese elderly. SUBJECTS:
      There were 72 Chinese elderly subjects aged 65 years and above, referred to the
      NUH Memory Clinic in the first year. RESULTS: Only 45 (62.5%) of the 72 subjects
      were diagnosed to have dementia using DSM III R criteria. There were 25 cases of
      Alzheimer's Disease and 20 multi-infarct dementia. In the non-demented group, 15
      (20.8%) had depression or anxiety disorders and 12 (16.7%), had no mental
      disorders but had physical illness which could affect memory. There was a highly
      significant difference in the ECAQ, CMT and CAS scores of demented and non
      demented elderly. There was also a significant difference in the cognitive
      performance of elderly with mild dementia and those with no mental disorder.
      CONCLUSION: The memory clinic is a useful facility for the diagnosis and
      management of dementia. The Cognitive Assessment Scale provides a valid and
      reliable battery of tests for dementia.

PMID- 9269378
TI  - Renocolic fistula as a complication to xanthogranulomatous pyelonephritis.
AB  - Four patients with xanthogranulomatous pyelonephritis were found to have
      renocolic fistulae. Coincidentally, the left kidney was involved in all four
      cases. All patients presented with renal mass. Two cases have had coexistent
      renal stones, one of them presented with massive upper gastrointestinal bleeding
      as a result of portal hypertension. Another patient had a history of
      Schistosomiasis. In none of the patients was the renal condition confidently
      diagnosed preoperatively, nor was the colonic fistula suspected. In all four
      patients, nephrectomy was performed together with resection of the involved colon
      followed by a satisfactory recovery. The possibility of a colonic fistula should
      be kept in mind as a complication to this rare renal condition in spite of the
      absence of colonic symptoms and normal finding in barium enema studies.

PMID- 9269379
TI  - A case of tracheal obstruction during oesophageal removal of a foreign body.
AB  - A patient was admitted with an impacted foreign body in the oesophagus. Repeated
      attempts to remove it during oesophagoscopy proved difficult and caused
      obstruction of the trachea during manipulation of the foreign body. A smaller
      endotracheal tube was subsequently placed in the trachea relieving the
      obstruction.

PMID- 9269380
TI  - Atrophie blanche--a special form of vasculopathy.
AB  - Although atrophie blanche is classified as a vasculitis, its presentation and
      management differ from the classical vasculitis. We present a patient with
      idiopathic atrophie blanche and discuss its management.

PMID- 9269382
TI  - Idiopathic intracranial hypertension, empty sella turcica and polycystic ovary
      syndrome--a case report.
AB  - Permanent visual loss is a well established major sequela of idiopathic
      intracranial hypertension (IIH). It is often insidious and frequently unnoticed
      by patients with IIH. It is vital to monitor these patients with serial
      perimetric and visual acuity tests because visual loss can be halted and
      occasionally reversed if treatment is begun early. We report a case of IIH with
      an empty sella turcica and polycystic ovary syndrome who developed visual field
      loss over ten years. This report illustrates the importance of close ophthalmic
      monitoring and detailed neurological and endocrinological evaluation to prevent
      complications in such patients.

PMID- 9269381
TI  - Radiological features in a patient with Kimura's disease.
AB  - Kimura's disease is an immune mediated inflammatory disorder that usually
      involves the head and neck region, primarily affecting the salivary glands,
      adjacent muscle and regional lymph nodes. Peripheral blood eosinophilia is the
      norm. Clinically and radiologically, it is difficult to differentiate Kimura's
      disease from salivary gland malignancy, lymphoma or haemangioma. The radiological
      findings of a patient who presented with a left facial mass involving the left
      parotid gland and the adjacent muscles are discussed. We also propose that the
      difference in the degree of enhancement between the initial and subsequent
      computed tomography study done two and a half years later may be due to the
      development of increased fibrosis and sclerosis as the disease progresses.

PMID- 9269383
TI  - An endoscopic diagnosis of appendicular intussusception in chronic appendicitis.
AB  - We report a rare case of chronic appendicitis causing recurrent intussusception
      in a 33-year-old man who had recurrent episodes of right iliac fossa pain
      diagnosed clinically and confirmed by colonoscopy. This is the first known case
      with the rare combination diagnosed endoscopically.

PMID- 9269384
TI  - Ticlopidine induced cholestatic jaundice.
AB  - Ticlopidine hydrochloride (Ticlid) has been increasingly used as an antiplatelet
      agent. Some studies showed that it has higher efficacy in reducing stroke
      recurrence when compared to conventional aspirin. Side effects like
      gastrointestinal disturbances and blood dyscrasias are common but ticlopidine
      induced cholestatic jaundice has been reported only rarely. We present a case
      report on a patient who has ticlopidine-induced cholestatic jaundice.

PMID- 9269385
TI  - Clinics in diagnostic imaging (23). Traumatic rupture of the left iliac vein.
AB  - A 3-day-old male baby with neonatal necrotising enterocolitis had a central line
      (Cavafex No. 18) inserted through the left femoral vein for administration of
      parenteral nutrition. Forty-eight hours later, he developed progressive abdominal
      distention with evidence of free abdominal fluid. A contrast injection done
      through the left femoral vein revealed retroperitoneal leakage of contrast from a
      traumatic rupture of the left iliac vein. The intravenous catheter was removed
      and he was treated conservatively with eventual recovery.

PMID- 9269386
TI  - What you need to know: addiction--cough mixture.

PMID- 9269387
TI  - Rheumatic fever is a major cause of acquired heart disease in children and young
      adults throughout the developing world.

PMID- 9269389
TI  - Living, dying, death and advance directives.

PMID- 9269388
TI  - Cefuroxime compared to amoxicillin-clavulanic acid in the treatment of community
      acquired pneumonia.

PMID- 9269390
TI  - Advance directive--a surgical viewpoint.

PMID- 9269391
TI  - Eye diseases in old age.

PMID- 9269392
TI  - Advance directive: a study on the knowledge and attitudes among general
      practitioners in Singapore.
AB  - Recent calls for the Advance Directive (AD) to be implemented in Singapore have
      raised issues regarding the dearth of knowledge and attitude among local
      healthcare professionals. The present study aims to find out the attitudes and to
      assess the extent of knowledge regarding the AD among General Practitioners (GPs)
      in Singapore. This was a cross-sectional, descriptive survey with a sample size
      of 199 doctors randomly drawn from the Singapore Medical Council list, forming a
      sampling fraction of 16%. The response rate obtained was 78%. The results showed
      that while GPs generally supported the concept of the AD, their views were
      divided on the issue of legislation. They had a basic knowledge of the AD, such
      as the definition of the AD, that it could be revoked, and the continuity of care
      and pain relief even after withdrawal of life-sustaining measures. However, only
      half knew when it should be executed. Many GPs were concerned that the
      legislation of the AD would lead to the acceptance of euthanasia. They believed
      that they were in the best position to decide on the treatment of choice for
      their patients, although they would respect their patients' wishes.

PMID- 9269393
TI  - Eye diseases in the elderly in Singapore.
AB  - OBJECTIVE: The study was conducted to determine the prevalence rates of blindness
      and visual impairment in those aged 60 years and above in Singapore and to
      determine the pickup rate of undiagnosed eye diseases through an active screening
      programme. METHOD: A random frame of 3,000 elderly persons aged 60 years and
      above was obtained from the Ministry of Home Affairs in Singapore. They were
      invited by mail to attend eye screening at Hougang Senior Citizens' Health Care
      Centre. The eye screening was in two parts: the first part by a trained
      registered nurse or therapy aide and the second part by the ophthalmologist. For
      each respondent, autorefraction, tonometry, retinal photography and visual field
      analysis were done. Examination criteria and disease classification were modelled
      after the Framingham Eye Study. RESULTS: 574 subjects attended the screening,
      giving a response rate of 22.2%. The prevalence rates for blindness and visual
      impairment in the elderly screened were 3.0% and 15.2% respectively. The
      prevalence rates for cataract, age-related macular degeneration, glaucoma and
      diabetic retinopathy were 78.6%, 27.0%, 5.7% and 5.1% respectively. For every
      person known to have cataract, 2 were unknown; for every person with age-related
      macular degeneration, 154 were unknown. None of the 29 persons with diabetic
      retinopathy was diagnosed previously. CONCLUSION: Almost 1 in 5 of the elderly
      screened had some degree of visual disability. The rates of visual impairment and
      blindness were similar to those reported in other studies and indicate a
      significant burden of visually impairing diseases in the community.

PMID- 9269394
TI  - Patient education in the management of diabetes mellitus.
AB  - AIM: A patient education programme in the management of diabetes mellitus (DM)
      was piloted in a government polyclinic. This study aimed to evaluate the
      effectiveness of the education programme in improving knowledge of DM and skills
      in self-care in order to achieve long term control of DM. METHOD: The study was
      carried out on an intervention group of 183 diabetic patients who completed the
      education programme and a control group of 95 diabetic patients who attended the
      clinic during the period of the study. The patients were assessed on their
      knowledge of diabetes and their practice for good control of the disease (dietary
      practice, compliance, home monitoring) through a questionnaire. Long term control
      was assessed by their glycosylated haemoglobin levels. The education programme
      comprised individual counselling using a diabetes education guide, talks,
      videoshows and food displays. RESULTS: The intervention group showed a
      significant and greater improvement in the knowledge of the disease and self-care
      and in the dietary practice (taking more unpolished rice/high fibre food,
      reducing calories intake and cutting down oily/fatty food) when compared to the
      control group. Compliance with medication and the mean HbA1c levels were also
      improved in the intervention group. CONCLUSION: In this study the educational
      intervention was observed to have improved the diabetic patients' knowledge of
      the disease and self-care and the long term control of the disease. Patient
      education is thus an important component in the management of diabetes mellitus.

PMID- 9269395
TI  - Percutaneous transluminal coronary angioplasty in Singapore General Hospital in
      1995: a medical audit.
AB  - BACKGROUND: There are few reports which describe the outcomes of unselected
      groups of patients undergoing percutaneous transluminal coronary angioplasty
      (PTCA) locally. This study has undertaken to audit the outcome of patients
      undergoing elective PTCA at Singapore General Hospital. METHODS: Procedural data
      and acute outcomes were recorded prospectively in all patients undergoing PTCA
      over a 12 month period. A retrospective casenotes review of all patients were
      carried by independent observers to determine out-of-lab complications. RESULTS:
      Seven hundred and eight-two patients underwent PTCA in 1995. Acute angiographic
      success rate was 90.9% and early clinical success rate was 89% ie excluding
      death, coronary bypass surgery and non fatal myocardial infarction. There were
      only two deaths in the series (0.26%). CONCLUSION: The audit confirms the
      importance of a high volume PTCA cases to achieve excellent results. The data
      serve as a useful background for future comparison of outcomes.

PMID- 9269397
TI  - Bizarre ECG in head injury mimicking ventricular tachycardia.
AB  - Bizarre electrocardiographic (ECG) changes were found in an 18-year-old girl who
      had a subdural haematoma following head trauma. The initial diagnosis was of
      ventricular tachycardia (VT) and she was treated with intravenous anti-arrhythmic
      drugs and electrical cardioversion, but to no effect. It was later concluded that
      the ECG appearances were not of a ventricular arrhythmia but were the result of
      the intracranial pathology. ECG abnormalities related to head injuries have been
      reported on many occasions, and our case report illustrates how this can create
      difficulties for the attending clinicians.

PMID- 9269396
TI  - Caroli's disease: functional diagnosis using 99mTc diethyl-iminodiacetic acid
      (IDA) hepatobiliary scintigraphy.
AB  - A case of Caroli's disease is presented and the findings of various imaging
      modalities are discussed with emphasis on the role of Technetium 99mTc diethyl
      iminodiacetic acid scan in reaching the final diagnosis. The 'beaded' appearance
      of the dilated intrahepatic ducts seen in this scan is believed to be
      pathognomonic for this condition.

PMID- 9269398
TI  - Intraabdominal desmoplastic small round cell tumour in an 11-year-old boy.
AB  - A case of desmoplastic small round cell tumour (DSRCT) is presented. This
      aggressive and rare neoplasm predominantly affects males and is almost
      exclusively intraabdominal in location. It is unique in that neural, mesenchymal
      and epithelial markers are co-expressed. Despite multi-modal therapy, the
      prognosis is extremely poor. The present report details the clinical features and
      typical pathological findings of DSRCT in an 11-year-old boy, who succumbed to
      the disease 16 months after diagnosis despite multiple chemotherapeutic regimes.

PMID- 9269400
TI  - Electrocardiographic case: Q waves in ECG--a clue to diagnosis.

PMID- 9269399
TI  - Clinics in diagnostic imaging (24). Cervical spine instability in seronegative
      rheumatoid arthritis.
AB  - A 59-year-old man presented with neck pain and limb numbness. He also had
      bilateral symmetrical joint deformities of his hands and wrists. Cervical spine
      radiographs showed C 1/2 instability and features of rheumatoid arthritis.
      Magnetic resonance imaging demonstrated erosion ofthe odontoid peg by pannus. C
      1/2 surgical fusion was performed. The role of imaging in cervical spine
      involvement by rheumatoid arthritis is reviewed.

PMID- 9269401
TI  - What you need to know: prescribing hormone replacement therapy.

PMID- 9269402
TI  - A diagnostic dilemma in an elderly patient with bone pains.
AB  - A 61-year-old patient presented with multiple bone pains. Biochemical,
      haematological and radiological investigations initially suggested a diagnosis of
      osteomalacia because of the presence of hypocalcaemia and looser zones. There
      were also multiple lytic bone lesions and bone scan showed multiple hot spots
      suggesting multiple bone secondaries. The key investigation in this case was
      examination of the bone marrow.

PMID- 9269403
TI  - Tarsorrhaphies are not enough in Crouzon's syndrome.

PMID- 9269405
TI  - Calcium-dependent O2 sensitivity of cat carotid body.

PMID- 9269406
TI  - Perfusion MRI assessment of cerebral blood flow and CO2 reactivity after
      controlled cortical impact in rats.

PMID- 9269407
TI  - Histological assessment of rodent CNS tissues to EPR oximetry probe material.
AB  - The effects of the paramagnetic oxygen sensing material, lithium phthalocyanine
      (LiPc) and fusinite were assessed in the brain of Mongolian gerbils and the
      spinal columns of rats respectively, to determine if there are histologically
      discernible changes in the tissue surrounding the probe material. This
      information is essential for the evaluation of the role of EPR oximetry in the
      measurements of pO2 in the CNS; the technique has great potential value for such
      measurements because it reports on the pO2 accurately and sensitively and, after
      the initial placement, measurements can be made repeatedly without invasive
      procedures or anesthesia. Histologic assessments demonstrated the inert nature of
      both the fusinite and LiPc EPR probes in rodent CNS tissue over relatively long
      (2 month) time periods. The fusinite suspensions and LiPc crystals (size range of
      approximately 100-200 microns) remained well localized to the point of injection
      and created mild acute tissue reaction on implantation (which appeared to resolve
      quickly) and virtually no tissue reaction at later times. The majority of the
      implanted fusinite and LiPc material was present extracellularly in the brain and
      spinal cord. MRI provided an accurate, noninvasive assessment of probe placement
      and was able to investigate pathologic effects (hemorrhage, edema, necrosis)
      associated with the probe placement and treatment effects.

PMID- 9269408
TI  - Regional differences in metabolism and intracellular pH in response to moderate
      hypoxia.

PMID- 9269409
TI  - Effect of anesthesia on cerebral tissue oxygen and cardiopulmonary parameters in
      rats.

PMID- 9269410
TI  - The functioning gerbil brain in vivo. Correlation between 31P NMR spectroscopy
      and the multiparametric monitoring approach.

PMID- 9269411
TI  - Determination of the PCO2-dependent component of the H+ concentration in venous
      and arterial blood plasma.
AB  - In normal venous blood plasma, the regression line of [H+] plotted against the
      PCO2 was linear against the square root of PCO2. Sequential measurements in
      venous and arterial blood of PCO2 and [H+] showed that the venous-arterial (V-A)
      difference in [H+] was linearly related to the V-A difference in the square root
      of PCO2, the regression line having the same slope as that of the venous [H+]
      plotted against the square root of PCO2. These findings suggested that the venous
      [H+] on the regression line represents the PCO2-dependent component, of [H+],
      [H+]*. The PCO2-independent component, delta [H+], can then be given by
      subtracting [H+]* from the measured [H+]. The delta [H+] in venous blood agreed
      well with that in arterial blood with a correlation coefficient of 0.99,
      supporting the validity of the value of [H+]*.

PMID- 9269412
TI  - Activation of tyrosine hydroxylase in striatum of newborn piglets in response to
      hypocapnic ischemia and recovery.
AB  - The present study describes the effect of hypocapnic ischemia caused by
      hyperventilation on striatal levels of dopamine, DOPAC, HVA and activity of
      tyrosine hydroxylase in striatal synaptosomes isolated from the brain of newborn
      piglets. Hyperventilation did not result in statistically significant changes in
      the striatal level of dopamine and its major metabolites; however, it was
      observed that after 20 min of recovery the levels of striatal tissue dopamine,
      DOPAC and HVA increase by 195%, 110% and 205%, respectively. The level of DOPA
      (3,4-dihydroxyphenylalanine), which was used as an index of tyrosine hydroxylase
      activity, also increased after recovery. The rate of dopamine synthesis was 32
      pmoles/mg protein/10 min in control piglets and after recovery this increased to
      132 pmoles/mg protein/10 min. Measurement of the tyrosine hydroxylase activity in
      Triton X-100 treated synaptosomes showed that, after 20 min of recovery, there
      was an increase in Vmax with no change in K(m) for pteridine cofactor, compared
      to control. This is consistent with the enzyme having been covalently modified
      (activated) during tissue ischemia caused by hyperventilation and remaining
      activated well into the recovery period. We postulate that ischemia can induce
      long lasting alterations in dopamine synthesis, which may play some role in
      mediation of hypoxic cell injury in immature brain.

PMID- 9269413
TI  - Metabolic mechanisms of anoxia tolerance in the turtle brain.

PMID- 9269414
TI  - Age-related changes in brain metabolism and vulnerability to anoxia.

PMID- 9269415
TI  - [Base excess] vs [strong ion difference]. Which is more helpful?
AB  - Blood [base excess] ([BE]) is defined as the change in [strong acid] or [strong
      base] needed to restore pH to normal at normal PCO2. Some believe that [BE] is
      unhelpful because [BE] may be elevated with a "normal" [strong ion difference]
      ([SID]), where a strong ion is one that is always dissociated in physiological
      solution, and where [SID] = [strong cations]-[strong anions]. Using a computer
      simulation, the hypothesis was tested that [SID] = [SID Excess] ([SIDEx]), where
      [SIDEx] is the change in [SID] needed to restore pH to normal at normal PCO2. The
      most current version of the plasma [SID] ([SID]p) equation was used as a
      template, and an [SIDEx] formula, of the Siggaard-Andersen form, derived:
      [SIDEx]p = [HCO3-]p -24.72 + (pHp - 7.4) x (1.159 x [alb]p + 0.423 x [Pi]p).
      [SID] was compared to [SIDEx] over the physiologic range of plasma buffering, and
      it was found that [SIDEx] varied by approximately 15 mM at any given [SID],
      thereby faulting the hypothesis. It is concluded that [SID] can be "normal" with
      an elevated [SIDEx], the latter being an expression of the [BE] concept, and a
      more helpful quantity in physiology. The "metabolic" component of a given acid
      base disturbance is usually estimated as whole blood [base excess] ([BE]WB),
      where [BE]WB is defined as the change in [strong acid] or [strong base] needed to
      restore plasma pH (pHp) to 7.4 at PCO2 of 40 Torr. However, the [BE] approach has
      been criticized as "inadequate for interpretation of complex acid-base
      derangements such as those seen in critically ill patients." The proposed
      alternative is the strong ion difference (SID) method, where a strong ion is one
      that is always dissociated in solution, and where [SID] = [strong cations] -
      [strong anions]. On the one hand, it does not seem possible, by the definitions
      of these entities, to change [SID] without also changing [BE]. On the other hand,
      a selected group of critically ill patients with hypoproteinemia has been
      reported in whom [SID] was "normal" (i.e. approximately 40 mEq.l-1) but [BE]WB
      clearly increased. The idea was that hypoproteinemia caused the alkalosis, due to
      a deficiency of plasma weak acid buffer, necessitating increased [HCO3-]p to
      maintain electrical neutrality. How could [SID] be "normal," but [BE] increased?
      The purpose of the current exercise was to address this question. An [SID excess]
      ([SIDEx]) formula was developed, conceptually identical to Siggaard-Andersen's
      [BE], and [SID] was compared to [SIDEx] over the physiological range of plasma
      [albumin] ([alb]p), plasma [phosphate] ([Pi]p), and plasma pH (pHp).

PMID- 9269416
TI  - [Base excess] and [strong ion difference] during O2-CO2 exchange.
AB  - Detecting uptake or production of "metabolic acid" by a given tissue is often of
      interest. [Base excess] ([BE]) is the change in [strong acid] or [strong base]
      needed to restore pH to normal at normal PCO2. However, [BE] seems to have the
      potential for minor inaccuracy during hypercarbia, and venous blood is
      hypercarbic relative to arterial. Another approach is [strong ion difference]
      ([SID]), where a strong ion is one that is always dissociated in solution, and
      where [SID] = [strong cation] - [strong anion]. The hypothesis was tested that a
      v [SID]p might be used to detect metabolic acid uptake or production by tissue. A
      computer simulation of O2-CO2 exchange was performed, using the Siggaard-Andersen
      [BE] equations, which provide an existing conceptual template. It was assumed
      that a change in [BE] = a change in [SID] (Adv. Exp. Med. Biol., in press). (A-v)
      [SID]p decreased linearly with decreasing [HbO2] during equimolar O2-CO2 exchange
      (delta mEq [SID]p.l-1 per delta gHbO2.dl-1 = 0.6, r2 = 1.0), and erythrocyte [BE]
      ([BE]e) and [SID]e decreased commensurately, such that [BE]WB remained constant.
      These changes represent ion exchanges between erythrocyte and plasma, governed by
      the Gibbs-Donnan equilibrium. It is concluded that a-v [SID]p may be used to
      examine a-v differences in [metabolic acid], based in [BE] concepts. The
      concentration of "metabolic acid" ([metabolic acid]) in blood increases during
      endotoxemia, exercise and shock. To identify organ(s) responsible, it is
      necessary to measure arteriovenous [strong acid]. Two methods are available.
      Whole blood base excess ([BE]WB), is the change in [strong acid]WB or [strong
      base]WB needed to restore plasma pH (pHp) to 7.4 at PCO2 of 40 torr, and is an
      excellent method for distinguishing "respiratory," from "metabolic" acidosis in
      arterial blood. However, while [BE] is most helpful conceptually, use of [BE] in
      venous blood presents two problems. First, [BE]WB may employ in vitro assumptions
      that are slightly inaccurate during hypercarbia in vivo, and venous blood is
      hypercarbic relative to arterial. The problem seems to be that [BE] assumes
      greater [hemoglobin] ([Hb]) than is actually effective in vivo, where Hb is
      diluted in the extracellular volume. The "Van Slyke" version of the [BE]WB
      equation is: BE]WB = ?[HCO3-]p - 24.4 + (2.3 x [Hb] + 7.7) x (pHp - 7.4)? x (1
      0.023 x [Hb]) (1) This equation may be thought of conceptually as: [BE] = ([HCO3
      ] + [A-]) - (normal [HCO3-] + normal [A-]) (2) where A- is negatively charged non
      volatile weak acid. Missing or excess charges are attributed to abnormal [strong
      acid] or [strong base], and [A-]WB is computed using actual, as opposed to
      effective, [Hb]. This problem has been adequately addressed in arterial blood by
      standard [BE]WB ([SBE]WB), by assuming that effective [Hb] in vivo is
      approximately one third of that in vitro. However, it is not clear whether this
      assumption is sufficiently accurate to examine arteriovenous differences. A
      second and related problem with using [BE] to detect (a-v) differences is the
      magnitude of change in Hb buffering in vivo during O2 desaturation. Desaturation
      renders Hb a stronger weak acid buffer, i.e. increases its effective pK value.
      Consequently, [HCO3-]p is greater at any given PCO2, creating the appearance of a
      larger [BE]WB, whereas [strong acid] or [strong base] has not changed. This
      artifact can be corrected using the "O2 desaturation transform factor," which is
      0.19 mM delta g [HbO2].dl-1 in vitro. In vivo, however, the magnitude of the O2
      desaturation transform factor might be different. An alternative approach to acid
      base analysis is strong ion difference (SID) where a strong ion is one that is
      always dissociated in physiologic solution. [SID] can usually be approximated as:
      [Na+] + [K+] - [Cl-] - [La-]. Although [BE] does not equal [SID], a change in
      [BE] must always accompany a change in [SID], and vice-versa. While the [SID]
      approach is tedious, and often unnecessarily so, [SID] ca

PMID- 9269418
TI  - Clinical value of transcutaneous PO2 assessment during hyperbaric oxygen therapy.

PMID- 9269417
TI  - Response of cortical oxygen and striatal extracellular dopamine to metabolic
      acidosis in newborn piglets.
AB  - This study determined the relationships of metabolic acidosis, cortical oxygen
      pressure, and striatal extracellular dopamine in the brain of newborn piglets.
      After a baseline period of 120 minutes, a 0.6 N HCl solution was infused
      intravenously to decrease the blood pH to about 7.0-7.05. The metabolic acidosis
      was then corrected by injecting sodium bicarbonate and measurements were
      continued for one hour. The results show that decreased blood pH to about 7.2
      7.15 does not cause a statistically significant change in mean blood pressure,
      cortical oxygen pressure or striatal extracellular dopamine. Further decrease in
      pH caused significant decrease in both blood pressure and cortical oxygen
      pressure. By the end of the period of acidosis the cortical oxygen pressure
      decreased from the control value of 43 +/- 4 Torr to 22 +/- 8 Torr. Changes in
      the extracellular level of striatal dopamine were parallel to changes in cortical
      oxygen pressure. The extracellular dopamine increased to 1270% of the control on
      the end of HCl injection. Infusion of bicarbonate to correct the acidosis
      resulted in an increase of cortical oxygen and progressive decline of dopamine in
      the extracellular medium. It is suggested that the level of extracellular
      dopamine in the striatum of newborn piglets was not directly affected by decrease
      in pH but was dependent on changes in tissue oxygen pressure during metabolic
      acidosis.

PMID- 9269419
TI  - Coronary flow response after myocardial ischemia may predict level of functional
      recovery.
AB  - Is there a quantity, potentially measurable in the operating theater, which
      predicts rapid recovery of heart power output after surgical intervention with
      ischemia? We have enhanced our blood-perfused, ejecting, isolated rat heart model
      for use inside the magnet of an NMR spectrometer, in order to conduct fundamental
      research into cardioprotective techniques. To provide a baseline, we investigated
      the effect of normothermic ischemic insults of varying duration. Hemodynamic and
      metabolic data were collected, and analyzed to seek measures predictive of rapid
      recovery of aortic power output, which was selected as the most important measure
      of function. The presence of erythrocytes in the perfusate ensures that oxygen
      supply is sufficient to support a physiological workload, and that there is
      reserve coronary flow. On reperfusion, reactive hyperemia occurs: coronary flow
      increases to a peak, then declines to a steady value. This response was
      mathematically modeled, and the data for each of fifteen experiments were fitted
      to the model. Correlating power output recovery against time to reach peak
      coronary flow yielded the following equation: R = -0.45 log10tp + 1.74 where R is
      the ratio of power output ten minutes after reperfusion to that before the
      ischemic insult, and tp is the time taken to reach peak coronary flow, in
      seconds. The correlation is very significant (p = 0.005). In the clinic, coronary
      flow response on reperfusion could be used to predict the patient's need for post
      operative support.

PMID- 9269420
TI  - Myocardial adaptation to acute oxygen shortage. A kinetic analysis.

PMID- 9269421
TI  - A method to determine red blood cell spacing in capillaries of rat heart.

PMID- 9269422
TI  - Oxygen transport to ischemic cardiac myocytes.

PMID- 9269423
TI  - The S factor--a new derived hemodynamic oxygenation parameter--a useful tool for
      simplified mathematical modeling of global problems of oxygen transport.
AB  - We describe a new derived hemodynamic oxygenation parameter, the S factor (S).
      The factor is based on oxygen delivery and oxygen consumption and can range from 
      3 to 1. It allows simplified mathematical modeling of clinical problems of oxygen
      transport and can be applied to many clinical situations. A new hemodynamic
      oxygenation parameter, the S factor (S), is introduced as an aid to mathematical
      modeling. It is defined as follows: [formula: see text] (DO2 = oxygen delivery,
      VO2 = oxygen consumption) S can theoretically vary from -3 (DO2 = VO2) to +1 (VO2
      = 0). When DO2/VO2 = 4 (ie. OER = 0.25), S = 0. An S < 0 implies utilization of
      reserve oxygen transport capacity. An S > 0 implies increased oxygen delivery in
      relation to oxygen consumption (ie. "shunted oxygen delivery"). By algebraic
      manipulation and substitution of the components of DO2 into Equation 1: DO2 = Q x
      Ca x 10 DO2 = Q [(Hb)(Sat)(1.36) + PaO2(.0031)] 10 (2) the following equations
      can be derived: [formula: see text] [formula: see text] Ca - Cv (Ca = arterial
      content, Cv = venous content) can be determined by substituting components of
      oxygen consumption: VO2 = Q (Ca - Cv) x 10 (5) into equation 1 and solving for Ca
      - Cv. [formula: see text] Equation 6 can be simplified to: [formula: see text] A
      previously defined relationship between mixed venous PO2 (PvO2) and DO2/VO2
      (where calculated P50 is 26.6 +/- 1.0) can be used to modify S in a clinically
      relevant manner. PvO2 = 5.44D O2/VO2 + 18.16 (8) The relationship between S and
      PvO2 can be defined by substituting Equation 4 into Equation 1 and solving for
      PvO2 PvO2 = [21.76/(1-S)] + 18.16 (9) As an example, at a PvO2 of 28 torr
      (anaerobic threshold), S = -1.2. The relationship between PvO2 and S is shown in
      Figure 1. S, which can also be defined as 1-4(VO2/DO2) or 1-4(OER), is a useful
      tool for mathematical modeling of global problems of oxygen transport because the
      previously derived equations with the S value allow the components of oxygen
      transport to be interrelated in a clinically relevant manner. Additional
      advantages of using S in mathematical modeling are: 1. Conceptually it 'fits' in
      that in regards to the sign (+ or -), as a -S implies utilization of reserve
      oxygen transport capacity and a +S implies wasted or excess oxygen delivery
      (shunted). 2. These concepts are easily quantified using the S factor. 3. It
      'spreads out' the difference between values for parameters (OER or S) integrating
      components of oxygen transport, ie. in the 'normal state' regarding oxygen
      transport, OER = 0.25 and S = 0. At the anaerobic threshold (PvO2 = 28 torr), OER
      = 0.55 and S = -1.2. Thus, the change in OER from 'normal state' to anaerobic
      threshold is 0.3 (0.55-0.25) and the change in S is 1.2. This represents a four
      fold increase. Four examples of mathematical modeling of global problems of
      oxygen transport using the S factor are described below.

PMID- 9269424
TI  - Evaluation of myoglobin function in the presence of axial diffusion.
AB  - Facilitation of oxygen transport by myoglobin has been assessed by many
      researchers. Yet, the models used in these studies often assume that radial
      diffusion is the primary transport mechanism in tissue. Axial diffusion is
      typically neglected. In this study, oxygen transport by myoglobin facilitation is
      added to a proven cardiac tissue model which contains axial diffusion in the
      tissue and capillary regions, the Radially-Averaged, Axially-Distributed (RAAD)
      model. Previous research has shown that the axial diffusion in the capillary and
      tissue regions becomes coupled, causing a reduction in the pO2 at the capillary
      inlet. The objective is to determine if this coupling effect increases the
      facilitation of oxygen transport by myoglobin. The RAAD model consists of non
      interacting cylinders of tissue (Krogh cylinders), with each perfused by a
      central capillary. Derivation of the equations describing the RAAD model yields a
      stiff, fourth-order, non-linear, ODE, BVP. The equation set is solved
      numerically. Parameters for myoglobin concentration and diffusion coefficient are
      chosen to maximize myoglobin facilitation. The effect of myoglobin is assessed by
      observing changes in the pO2 profiles for the model with and without myoglobin.
      Also, the RAAD model is compared to experimental pO2 data to determine if the
      inclusion of myoglobin improves the model prediction. The computer simulations
      show that myoglobin does facilitate diffusion, but only to a small extent. The
      changes in the capillary pO2 profiles for the model with and without myoglobin
      are not significant, pO2 reductions are 0.8% at the inlet and 2% at the outlet.
      The model prediction is not substantially improved with the addition of
      myoglobin. The sum of squared error is reduced by 0.1%, from 5.6834 without
      myoglobin, to 5.6779 with myoglobin. The steady state solution of the RAAD model
      with myoglobin suggests that, in the presence of axial diffusion, facilitation of
      oxygen diffusion to tissue is not myoglobin's primary function. No conclusion can
      be made about the transient function of myoglobin.

PMID- 9269425
TI  - Myocardial oxygen tension and capillary density in the isolated perfused rat
      heart during pharmacological intervention.
AB  - Oxygen is essential for normal cardiac function and plays an important role in
      cardiac regulation. Electron paramagnetic resonance (EPR) oximetry appears to
      have some significant advantages for measuring oxygen tension (pO2) in the
      beating heart. This study presents the serial measurement of myocardial pO2 by
      EPR oximetry in the isolated crystalloid perfused heart during treatment with
      different cardioactive drugs: dobutamine, metoprolol, verapamil, vasopressin, and
      N omega-Nitro-L-Arginine Methyl Ester (L-NAME). Baseline myocardial pO2 was 176
      +/- 14 mmHg (mean +/- S.E.). Myocardial capillary density in the intact
      contracting heart was calculated to be 2300 +/- 100 mm-2, using local myocardial
      pO2 and a cylindrical model for oxygen diffusion in tissue. Each drug had
      characteristic effects on myocardial pO2, myocardial oxygen consumption (MVO2),
      and capillary density. Metoprolol and verapamil increased myocardial pO2 by 51%
      and 18%, respectively, dobutamine decreased myocardial pO2 by 84% while
      vasopressin and L-NAME had no significant effect on myocardial pO2. Metoprolol
      and verpamil decreased MVO2 by 9% and 56%, respectively, while dobutamine
      increased MVO2 by 59%. A quantitative comparison of effects on the capillary bed
      based on changes in myocardial pO2 and MVO2 was made. Metoprolol and verapamil
      had opposite effects on the capillary bed. Verapamil decreased myocardial
      capillary density by 39%, while capillary density increased by 10% (n.s.) with
      metoprolol. Data following perfusion without drug is also presented. We conclude
      that: 1) The application of EPR oximetry with LiPc provides dynamic evaluation of
      local myocardial pO2 in the contracting heart. 2) Using a cylindrical model of
      oxygen delivery and diffusion in tissue, these data may be used to describe the
      changes of capillary density during pharmacological interventions.

PMID- 9269426
TI  - Influence of isokinetic and ergometric exercises on oxygen partial pressure
      measurement in the human knee joint.
AB  - We conducted the first in vivo investigation on the influence of joint movement
      on intraarticular oxygen partial pressure. The development of a special flexible
      microcatheter allowed measurements of intraarticular oxygen partial pressure
      under both physiological and pathological conditions. The aim of this study was
      to evaluate the influence of different knee joint stresses on intraarticular
      oxygen partial pressure under physiological (healthy patients) and pathological
      (patients with osteoarthritis) conditions. The results show that the different
      exercise patterns influence the intraarticular oxygen partial pressure. Patients
      with osteoarthritis showed a lower increase of intraarticular oxygen partial
      pressure compared with healthy patients. This phenomenon is directly correlated
      to the degree velocity of the isokinetic exercises. We found the same results
      under ergometric conditions. This method allows functional, intraarticular in
      vivo measurements under different exercise patterns. For the first time, we were
      able to measure the influence of joint movement on the intraarticular process of
      nutrition under physiological and pathological conditions. Also, to evaluate for
      the first time in vivo different concepts for osteoarthritis therapy.

PMID- 9269427
TI  - The equivalent Krogh cylinder and axial oxygen transport.
AB  - The Krogh-Erlang model has served as a basis of understanding of oxygen supply to
      resting and working muscle. Considerable discrepancy was found between pO2
      microsensor data and results from that model. A modification was made to the
      transport mechanisms implied by the Krogh-Erlang model by averaging the tissue
      radially, using a mass-transfer coefficient to maintain radial transport, and
      adding axial diffusion in the capillary and tissue. This radially-averaged,
      axially distributed (RAAD) modified Krogh model is used to evaluate the
      hypothesis that axial transport is important in Krogh-geometry capillary-tissue
      structures. Analytic solutions for the modified model were developed. RAAD model
      histograms bear a striking resemblance to experimental data, while results from
      the classic model do not. The former has an SSE (sum of squared error) of 10.2
      with respect to experimental histograms, while the Krogh model has an SSE of
      238.6. The effect of using a radial mass-transfer coefficient was evaluated by
      comparing the RAAD model with a fully distributed model. It had been shown that
      the modified Krogh model predicts tissue level data well when the length-to
      tissue radius ratio is 50. It was expected that the predictions would be degraded
      for smaller ratios and then the Krogh model would suffice. By supplying a fixed
      volume of tissue at different radius/length ratios, it will be shown that the
      modified Krogh model is superior in all aspects to the Krogh model. The results
      are slightly different from those of the distributed model, but these differences
      are limited to the first 10% of the arteriolar region. It is concluded that the
      RAAD model is a better overall predictor of oxygen distribution and may be useful
      in furthering our understanding of oxygen transport to tissue in hemoglobinless
      perfusion situations. We suggest that this radially-averaged, axially-distributed
      model be used in place of the classic Krogh cylinder model for all biological
      situations.

PMID- 9269428
TI  - Influence of O2-Hb kinetics and the Fahraeus effect on the arteriolar role in gas
      exchange.

PMID- 9269429
TI  - Can NMR diffusion-weighted imaging provide quantitative information on tumor
      interstital pO2?

PMID- 9269430
TI  - Evaluation of the concept of "hypoxic fraction" as a descriptor of tumor
      oxygenation status.
AB  - The presence and significance of tumor hypoxia has been recognized since the
      1950's. Hypoxic cells in vitro and in animal tumors in vivo are documented to be
      three times more resistant to radiation-induced killing compared to aerobic
      cells. There is now evidence that tumor hypoxia is treatment-limiting in many
      human cancers. One common way to describe the extent of hypoxia in individual and
      groups of tumors is the "hypoxic fraction." This measurement infers that cells
      are present in only two radiobiologically significant states: oxygenated and
      hypoxic. In this paper, we demonstrate the qualitative and quantitative presence
      of hypoxic tumor cells using the oxygen dependent metabolism of the 2
      nitroimidazole, EF5. Two assumptions concerning the calculation and
      interpretation of the hypoxic fraction are considered. The first is the use of
      multiple animals to describe the radiation response at a given radiation dose. We
      hypothesize that the presence of intertumor variability in radiation response due
      to hypoxia could negatively influenced the characterization of the change in
      slope required to calculate the hypoxic fraction. The studies presented herein
      demonstrate heterogeneity of radioresponse due to hypoxic fraction within and
      between tumor lines. The 9L subcutaneous tumor studied in air-breathing rats
      demonstrates a 2 log variation in surviving fraction at 17 Gy. The Morris 7777
      hepatoma, in contrast, showed little variability of radiation response. Our
      second question addresses the limitations of using the "hypoxic fraction" to
      describe the radiation response of a tumor. This calculated value infers that
      radiobiological hypoxia is a binary measurement: that a tumor contains two cell
      populations, aerobic cells with maximal radiosensitivity and hypoxic cells with
      maximal radioresistance. The classic work of Thomlinson and Gray, however,
      implies the presence of an oxygen gradient from tumors vessel through the
      tissues. In both the 9L and Q7 tumors, flow cytometric analysis of EF5 binding
      demonstrates a continuous range of cellular pO2 levels. These studies suggest
      that: 1) there is extensive intertumor variability of radiation response in
      certain tumor lines; 2) the variability in radiation response between individual
      tumors in a group may affect the ability to describe a particular tumor type's
      "hypoxic fraction" and 3) The oxygen status of tumor cells is a continuum. This
      realization affects the ability to apply a binary concept such as the "hypoxic
      fraction" effectively in radiobiology.

PMID- 9269432
TI  - Potential for EPR oximetry to guide treatment planning for tumors.

PMID- 9269431
TI  - Optical imaging of breast tumor by means of continuous waves.

PMID- 9269433
TI  - Vascularization, blood flow, oxygenation, tissue pH, and bioenergetic status of
      human breast cancer.

PMID- 9269434
TI  - Oxygen tensions in rodent tumors after irradiation with neutrons.
AB  - We started investigations on intratumoral oxygen tension after irradiations with
      reactor fission neutrons using the Eppendorf-pO2 Histograph. Isotransplanted AT17
      mammary carcinomas on C3H-mice and osteosarcomas OTS-64 on balb C-mice received 2
      or 6 Gy neutrons single dose. Before and at certain points of time after
      treatment the pO2 values were evaluated. Some tumors with initially low median
      pO2 values showed a short-lasting increase between 2 and 24 h after irradiation.
      In those tumors with relatively high pretherapeutic pO2 values the pO2 decreased
      to the range of hypoxia. A third group of tumors showed no marked changes after
      irradiation. No tumor stopped growth during the observation period.

PMID- 9269435
TI  - Peripheral perfusion and tissue oxygenation improvement induced by
      antihypertensive medication combined with lipoidoproteinosis treatment.

PMID- 9269436
TI  - PO2-dependent glomerular ultrafiltration of middle-weight protein is modified by
      protective amino acids.

PMID- 9269437
TI  - Fixed acid uptake by visceral organs during early endotoxemia.

PMID- 9269438
TI  - Release of lactate by the lung in acute lung injury.

PMID- 9269439
TI  - Endothelial and sympathetic regulation of vascular tone in canine skeletal
      muscle.

PMID- 9269440
TI  - Colloidal gold particles as a marker of plasma perfusion and endocytosis in
      kidney, liver, and spleen.

PMID- 9269441
TI  - Mathematical modelling of local regulation of blood flow by veno-arterial
      diffusion of vasoactive metabolites.

PMID- 9269442
TI  - Regional cerebral blood flow after subarachnoid hemorrhage (SAH) in the rat.

PMID- 9269443
TI  - Effect of hypoxic hypoxia on transmural gut and subcutaneous tissue oxygen
      tension.

PMID- 9269444
TI  - Effects of hemodilution and oxygen breathing on gut oxygenation in anesthetized
      dogs.

PMID- 9269445
TI  - Equal oxygen delivery may not result in equal oxygen consumption.

PMID- 9269446
TI  - Modification of low density lipoproteins by erythrocytes and hemoglobin under
      hypoxic conditions.
AB  - Oxidation of low density lipoprotein (LDL) has been implicated in atherogenesis.
      It has also been suggested that modification of LDL in the presence of
      endothelial and smooth muscle cells is associated with the production of
      superoxide. Red cells and hemoglobin have been shown to be a source for enhanced
      superoxide production under hypoxic conditions. We now show that incubation of
      LDL with both hemoglobin and erythrocytes under hypoxic conditions produces the
      increased Relative Electrophoretic Mobility (REM) associated with LDL oxidation.
      With hypoxic hemoglobin, this reaction is over within 10 minutes, appreciably
      faster than other in vitro methods for LDL oxidation. The increased REM was found
      to be associated with partial deoxygenation of hemoglobin indicative of
      appreciable oxygen utilization and a more hypoxic state. At later times, the
      modified LDL was found to produce enhanced hemoglobin oxidation. The resultant
      modified LDL was shown to have elevated TBARS indicative of LDL oxidation. In
      addition, it was found to induce smooth muscle cell proliferation which is one of
      the biological factors thought to be associated with atherogenesis. The
      relatively rapid LDL modification detected with hypoxic erythrocytes and
      hemoglobin suggest that even under in vivo conditions with the antioxidants
      present in plasma, oxidation may still occur in the circulation with the
      associated vascular damage occurring as the blood containing elevated levels of
      oxidized LDL leave the pulmonary circulation.

PMID- 9269447
TI  - Weak spots inside the myocardium of a Langendorff rat heart observed by NADH
      videofluorometry.

PMID- 9269448
TI  - Microvascular growth in the chicken chorio-allantoic membrane.

PMID- 9269449
TI  - Different enzyme activities in coronary capillary endothelial cells.
AB  - Differential distributions of alkaline phosphatase (AP) and dipeptydylpeptidase
      IV (DPPIV) were studied in coronary microvascular endothelial cells. Endothelial
      cells were obtained by the perfusion of coronary vessels with 0.1% trypsin PBS
      solution and cultured in uncoated culture dishes. Staining of cultured
      endothelial cells with AP- and DPPIV-sensitive reagents revealed blue or red
      staining, respectively. Most colonies showed cells of only one color, blue or
      red, even at the fifth passage. AP-sensitive cells, which were originally
      elongated, shortened and widened, proliferating to form monolayer colonies of
      cobble stone-like cells. AP-stainability became weak with repeated passages.
      DPPIV-sensitive endothelial cells remained elongated even after repeated
      passages. The cell shape and stainability seemed to be coupled and maintained
      through the five passages studied.

PMID- 9269450
TI  - Myocyte hypertrophy and capillarization in spontaneously hypertensive stroke
      prone rats.
AB  - Stroke-prone spontaneously hypertensive rats (SHRSP) are liable to suffer a
      stroke between 25 and 40 weeks of age. Left ventricular capillarity was studied
      in 40-week-old SHRSP to clarify the effects of hypertrophic changes in
      cardiomyocytes on oxygen transport capacity within the tissue. The innermost
      region of the left ventricular subendocardium at the level of the maximum
      diameter of the heart was investigated. Methods for sectioning and differential
      staining of arteriolar, intermediate and venular capillaries, and measurements
      for determining capillarity parameters were as previously described. Total
      capillary density decreased, while capillary domain areas increased along the
      whole capillary pathway. These changes in SHRSP seemed unfavorable for oxygen
      supply to ventricular tissues. To minimize the effects of the adverse changes,
      the ratio of the capillary to myocyte number increased markedly. The proportion
      of arteriolar capillaries increased and the venular proportion decreased.

PMID- 9269451
TI  - Adequacy of cerebral vascular remodeling following three weeks of hypobaric
      hypoxia. Examined by an integrated composite analytical model.

PMID- 9269452
TI  - Use of a PFC-based oxygen carrier to lower the transfusion trigger in a canine
      model of hemodilution and surgical blood loss.

PMID- 9269454
TI  - Longitudinal studies on the interaction of perfluorochemicals with liver
      cytochromes P-450 by means of testing the rate of detoxification of
      pentobarbital.
AB  - Four perfluorochemicals, Bis-[F-butyl]ethene, perfluorocyclohexylmorpholine,
      perfluorodecalin and perfluorooctylbromide were compared by their influence on
      the liver cytochrome P-450 system, measuring the pentobarbital sleeping time as
      defined by the time of loss of the righting reflex in rats. In all experiments
      first a prolongation of barbital detoxification was observed, which lasted at
      least 2-4 days. Thereafter a very long extended period of abbreviated sleeping
      time followed which was only missed after perfluoroctylbromide. Thus substrate
      competition, uncoupling of monooxygenation and enzyme induction determine the
      detoxifying processes in the liver that follow the administration of
      perfluorochemicals.

PMID- 9269453
TI  - Effect of perfluorochemical emulsion on hemorheology and shear induced blood
      trauma. Possible mechanisms and future applications.

PMID- 9269455
TI  - High oxygen partial pressure in tissue delivered by stabilized microbubbles.
      Theory.

PMID- 9269456
TI  - Effects of perflubron emulsion and 100% oxygen breathing on local tissue PO2 in
      brain cortex of unanaesthetized rabbits.

PMID- 9269457
TI  - Chromatographic process identification for protein C purification using frequency
      response analysis.
AB  - Frequency response analysis is applied for the analysis of liquid chromatography
      output of protein separation. Reduced data from simple chromatograms suggest that
      various Bode plot parameters, magnitude ratios, phase shift, the steady state
      gain, break frequency, and system order in the frequency domain, can be used to
      gain phenomenological insights on the system. Such an approach is advantageous
      because the validity of the model can be checked for two plots, the magnitude
      ratio vs. frequency and the phase shift vs. frequency, as compared to a single
      plot in the time domain. This approach also provides a useful empirical-tool
      which can be quantifiably used for process validation and scale-up, especially
      for immunoaffinity and immobilized metal affinity chromatographic systems used
      for protein C purification.

PMID- 9269459
TI  - Pulmonary delivery of human protein C and factor IX.

PMID- 9269458
TI  - Separation of recombinant human protein C from transgenic animal milk using
      immobilized metal affinity chromatography.
AB  - Protein C is an important serine protease due to its ability to proteolytically
      cleave activated Factors V and VIII. Excess coagulation and blood agglutination
      can lead to plugged capillaries, thereby reducing oxygen transport to
      interstitial tissues. To treat patients with hereditary and acquired protein C
      deficiency would require a greater amount of Protein C than that available from
      human plasma. However, the potential demand for this protein could be met by the
      production of human protein C from transgenic animal mammary glands. Thus,
      research into inexpensive, efficient methods to purify proteins from transgenic
      animal milk will be a critical area of study for the large scale production of
      protein C. Immobilized metal affinity chromatography (IMAC) is a novel method for
      the purification of protein C. A proposed method of purification is to take
      advantage of protein C's strong metal ion binding characteristics with IMAC to
      assist in the separation from transgenic animal milk. The separation procedure is
      benchmarked against current systems in use by the American Red Cross for
      purification of Protein C from transgenic porcine milk. Common problems in
      developing separation schemes for new therapeutics are the initial availability
      of the product (protein), and time-to-market concerns. Extensive experimental
      tests for scaleable purification schemes are often cost and time prohibitive. In
      order to optimize an IMAC protocol with minimal waste of time and resources,
      total quality management tools have been adopted. Initial experiments were
      designed to choose buffer conditions, eluents, immobilized valence metals, and
      flow rates using Taguchi experimental design, which is a total quality management
      (TQM) tool. One of the values of Taguchi methods lies in the use of Latin
      orthogonal sets. Through the use of the orthogonal sets, the total number of
      experiments may be reduced, shortening the focus time on optimal conditions.

PMID- 9269460
TI  - Reusable, real-time, immuno-optical protein C biosensor.
AB  - A Protein C (PC) biosensor can be used to diagnose PC deficiency, to monitor the
      PC level in the blood of PC deficient patients, and to measure the PC
      concentration in other PC-containing samples, such as PC producing animal cell
      culture broth or transgenic animal milk. A fully functional biosensor requires
      extremely high sensitivity and specificity, and real-time measurement. To satisfy
      these requirements, it is proposed to develop an immuno-optical fiber biosensor
      that utilizes PC-specific biomolecules (PC probes) tagged with fluorophores. The
      method involves immobilizing monoclonal antibody against PC (anti-PC) on the
      surface of an optical fiber. When PC in a sample is adsorbed to the anti-PC on
      the fiber, it can be reached with the fluorophore tagged PC-probe. The intensity
      of light transported through the optical fiber, therefore, can be correlated with
      the concentration of PC in the sample. The sensor will be designed so it can be
      reused, following a simple elution step, thus reducing diagnostic expense. The
      preliminary study shows encouraging future for the real-time optical PC
      biosensor.

PMID- 9269461
TI  - Effect of exercise and ischemia on tissue oximetry and cytochrome in normal
      subjects, patients with chronic limb pain, and patients with mitochondrial
      mitopathies.

PMID- 9269462
TI  - Measurement of cerebral venous saturation in adults using near infrared
      spectroscopy.

PMID- 9269463
TI  - Simultaneous assessment of cerebral oxygenation and hemodynamics during a motor
      task. A combined near infrared and transcranial Doppler sonography study.
AB  - During performance of a sequential finger opposition task we measured changes in
      regional cerebral blood oxygenation (rCBO) over the motor cortex and blood flow
      velocity changes (CBFV) in the middle cerebral artery in a combined near-infrared
      spectroscopy (NIRS) and transcranial Doppler Sonography (TCD) study. Stimulus
      duration was 60 followed by a 90 s rest period. During performance of the motor
      task we observed an increase in [oxy-Hb] a decrease in [deoxy-Hb] and an increase
      in MCA flow velocity. These changes were significantly more pronounced
      contralaterally than ipsilaterally to the moving hand. The time course of changes
      in [oxy-Hb] and CBFV were strikingly similar, showing a pronounced initial over
      shoot. This study proves the feasibility of a simultaneous assessment of
      microcirculatory hemodynamics and cerebral oxygenation at high temporal
      resolution.

PMID- 9269464
TI  - Length of resting period between stimulation cycles modulates hemodynamic
      response to a motor stimulus.
AB  - The influence of different lengths of the pre-stimulation resting period on the
      magnitude of a hemodynamic response evoked by motor stimulation was examined in
      10 subjects by means of near-infrared spectroscopy (NIRS). A motor stimulus was
      used which has been previously established as a model for functional activation
      studies with NIRS. Subjects performed a 20 s finger opposition task in the hand
      contralateral to NIRS probe localization over left sensorimotor area (C3',
      according to the 10-20 system). The duration of the pre-stimulation resting
      period was varied from 10s to 50s and response magnitude was assessed for each of
      the interstimulus intervals (10 s, 20 s, 30 s, 40 s and 50 s). Data analysis
      showed that response magnitude in oxygenated and deoxygenated haemoglobin
      concentration changed with different interstimulation intervals. Interestingly
      the greatest NIRS response was obtained with resting period 30 s prior to
      stimulation; shorter and longer resting periods resulted in smaller responses.
      The time course and the dependence of response magnitude on interstimulus
      interval differed between [oxy-Hb] and [deoxy-Hb] changes. For [oxy-Hb] the
      previously described fast initial increase ('overshoot') and the post-stimulation
      undershoot was more clearly seen with long prestimulation resting periods.
      Cytochromeoxidase oxygenation changes did not change significantly with different
      interstimulus intervals. We conclude that comparisons between different
      functional activation studies with techniques relying on stimulus evoked changes
      in cerebral hemodynamics must take into account not only the quality of the
      experimental paradigm and the length of the stimulation period, but also that the
      resting period between repetitive stimulations is important for response
      amplitude and its time course.

PMID- 9269465
TI  - Applications of NIRS for measurements of tissue oxygenation and haemodynamics
      during surgery.

PMID- 9269466
TI  - How to evaluate slow oxygenation changes to estimate absolute cerebral
      haemoglobin concentration by near infrared spectrophotometry in neonates.

PMID- 9269467
TI  - Effect of antioxidants on hyperoxia-induced ICAM-1 expression in human
      endothelial cells.
AB  - The regulating mechanism of hyperoxia-induced ICAM-1 expression has not been
      elucidated. We studied the effect of antioxidants, including superoxide dismutase
      (SOD), catalase and N-acetylcysteine (NAC), on hyperoxia-induced ICAM-1
      expression in human pulmonary artery endothelial cells (HPAEC) and human
      umbilical vein endothelial cells (HUVEC). Cells were cultured to confluence and
      exposed to either hyperoxic or normoxic gas with or without various kinds of
      antioxidants. The levels of ICAM-1 expression in the endothelial cells and the
      concentrations of reduced (GSH) and oxidized glutathione (GSSG) in the media were
      examined by flow cytometry and by spectrophotometry, respectively. After 48-hour
      exposure to hyperoxia, ICAM-1 expression was increased (HPAEC; 161 +/- 21% and
      HUVEC; 163 +/- 16%) and total glutathione concentration in the media was
      decreased as compared with normoxia. SOD did not change the GSH and GSSG
      concentrations in the media. Catalase dose-dependently decreased the supernatant
      GSSG concentration in both HPAEC and HUVEC, while the GSH concentration was
      nearly constant. NAC dose-dependently increased the supernatant GSH
      concentrations in both HPAEC and HUVEC. There was no difference in the
      supernatant GSSG concentrations between the NAC-treated HPAEC and HUVEC. There
      was no difference in ICAM-1 expression in either HPAEC or HUVEC with SOD
      treatment. ICAM-1 expressions in 100 U/ml (236 +/- 20%) and 1,000 U/ml (315 +/-
      36%) of catalase were increased in HPAEC, and that in 1,000 U/ml (440 +/- 209%)
      of catalase was increased in HUVEC. Five and 10 U/ml of NAC decreased ICAM-1
      expression in HPAEC (141 +/- 26% and 113 +/- 11%) and HUVEC (119 +/- 23% and 106
      +/- 7%), respectively. These results suggest that extracellular glutathione may
      play a role in regulating hyperoxia-induced ICAM-1 expression in HPAEC and HUVEC.

PMID- 9269468
TI  - Leukocyte adhesion in pial cerebral venules after PMA stimulation and
      ischemia/reperfusion in vivo.

PMID- 9269469
TI  - Nitric oxide inhibits growth of vascular smooth muscle cells in vitro by
      mechanisms independent of guanylate cyclase.

PMID- 9269470
TI  - Effects of puncturing on the measurement of local oxygen pressure using
      polarographic microelectrodes.

PMID- 9269471
TI  - Comparisons of measurements of pO2 in tissue in vivo by EPR oximetry and
      microelectrodes.

PMID- 9269472
TI  - Catchment depths of surface electrodes for H2 and O2 in tissue.

PMID- 9269473
TI  - Intrarenal pO2 measured by EPR oximetry and the effects of bacterial endotoxin.

PMID- 9269474
TI  - Measurements of oxygen tension in the rat kidney after contrast media using an
      oxygen microelectrode with a guard cathode.
AB  - The oxygen tension (PO2) in the rat kidney was studied by modified Clark
      microelectrodes. Changes in PO2 were measured in the renal cortex and outer
      medulla after intravenous injections of the X-ray contrast medium (CM)
      diatrizoate, 370 mg iodine/mg body weight. Injection of diatrizoate caused a
      slight fall in PO2 in the renal cortex (from 42 +/- 4 to 38 +/- 4 mm Hg). In the
      medulla PO2 decreased significantly (from 34 +/- 6 to 20 +/- 4 mm Hg). Ringer's
      solution did not induce any changes.

PMID- 9269475
TI  - Oxygen distribution in the vasculature of mouse tissue in vivo measured using a
      near infra red phosphor.
AB  - Oxygen dependent quenching of phosphorescence has been used to measure the
      oxygenation of tissue in mice, including the differences between normal tissue
      and that of a murine tumor. Approximately 0.3 mg of the phosphorescence oxygen
      probe, Green 2W, was injected into the tail vein of tumor bearing mice. The mice
      were immobilized using an anesthetic cocktail and illuminated with flashes (< 4
      microseconds t1/2) of light of 636 +/- 15 nm. The emitted phosphorescence (790 nm
      max.) was measured using an imaging phosphorimeter with an intensified CCD
      camera, an instrument which provides two dimensional digital maps of oxygen
      pressure. Both the illumination light and the phosphorescence were in the near
      infra red region of the spectrum, where skin and tissue have little absorption.
      The light can therefore readily pass through the skin and centimeter thickness of
      tissue. Mice are sufficiently small that the oxygen pressure maps could be
      obtained by illuminating from either the same or the opposite side as the camera
      (and tumor). The tumors were observed as regions with oxygen pressures
      substantially below those of the surrounding normal tissue. Thus, it is possible
      to non-invasively detect these tumors and to monitor their internal oxygen
      pressure in real time and through cm of tissue.

PMID- 9269476
TI  - In vivo 17O magnetic resonance spectroscopy. Determination of temperature effects
      on metabolic rates (Q10 factor).

PMID- 9269477
TI  - Imaging of oxygen distribution in the surface and deep areas of the kidney.

PMID- 9269479
TI  - Examples of in vitro-in vivo relationships with a diverse range of quality.

PMID- 9269478
TI  - Extended porphyrins. New IR phosphors for oxygen measurements.
AB  - Tetrabenzoporphyrins (TBP) of Zn, Pd, Lu, Y, Sn and Pb show strong absorption
      bands in the near IR region of the spectrum. Phosphorescence in dimethylformamide
      (DMF) solutions at room temperature was measured for Pd and Lu complexes giving
      quantum yields of 7.9% and 3.5% and lifetimes of 250 microseconds and 870
      microseconds, respectively. Pd meso-tetraphenyltetrabenzoporphyrin 1 (PdPh4TBP)
      shows a red shift of the absorption Q-band to 628 nm. 1 reacted with ClSO3H and
      obtained chlorosulfonato derivative 2 was converted to a set of water soluble
      chromophores: Pd meso-tetra(sulfophenyl)tetrabenzoporphyrin (Pd Ph4(SO3Na)4TBP)
      3, corresponding sulfonamide (Pd Ph4(PEG)4TBP) 4 with aminopolyethyleneglycol
      (Av.M.W. 5,000) and sulfonamide derivatives of glucoseamine (Pd
      Ph4(glucoseamine)4TBP) 5 and aminophenylacetic acid (Pd Ph4(phenac)4TBP) 6.
      Electronic absorption and phosphorescence spectra of 1 and some of its
      derivatives were recorded and phosphorescence quantum yields and lifetimes were
      measured for deoxygenated solutions. The oxygen quenching constants were measured
      for the water soluble complexes 3 and 4 and found to be suitable for oxygen
      measurements in vivo. Tetranaphthaloporphyrin (TNP) complexes of Pd and Lu as
      well as Pd meso-tetraphenyltetranaphthaloporphyrin (PdPh4TNP) were synthesized
      and their absorption and emission properties were examined.

PMID- 9269480
TI  - Dissolution assay development for in vitro-in vivo correlations. Theory and case
      studies.

PMID- 9269481
TI  - In vitro dissolution profile comparison and IVIVR. Carbamazepine case.
AB  - Dissolution data for the immediate or modified release drug products are usually
      collected as percent dissolved at multiple time points. Once an in-vitro/in-vivo
      relationship is established on a drug product, the dissolution profile becomes
      meaningful and important. In that context, if a firm desires to modify its
      formulation on which the in-vitro/in-vivo association has been established, a
      meaningful insight into the pharmacokinetics may be obtained by comparing the
      dissolution profiles of the two lots. In this presentation, we demonstrated a
      model dependent dissolution profile comparison approach using example of
      carbamazepine tablet dissolution data. Once a mathematical function was selected
      to describe the dissolution data coming from various standard lots, a similarity
      region could be constructed using the model parameter variances. To compare the
      test and reference lot dissolution profiles, a statistical distance was
      calculated between the mean parameters. A confidence region generated around the
      normalized mean statistical distance could then be compared with the similarity
      region to assess the similarity or dissimilarity of the dissolution profiles.

PMID- 9269482
TI  - A general framework for non-parametric subject-specific and population
      deconvolution methods for in vivo-in vitro correlation.

PMID- 9269483
TI  - Convolution-based approaches for in vivo-in vitro correlation modeling.
AB  - One approach to in vivo-in vitro correlation (IVIVC) for extended release (ER)
      oral dosage forms is to directly model the relationship between the time courses
      of in vitro release and plasma drug concentrations. For drugs that exhibit
      linear, time-invariant disposition this can be done using models based on the
      convolution integral. Advantages of this approach relative to deconvolution-based
      IVIVC approaches include the following: The relationship between measured
      quantities (in vitro release and plasma drug concentrations) is modeled directly
      in a single stage rather than via an indirect two stage approach. The model
      directly predicts the plasma concentration time course. As a result: The modeling
      focuses on the ability to predict measured quantities (not indirectly calculated
      quantities such as the cumulative amount absorbed). The results are more readily
      interpreted in terms of the effect of in vitro release on conventional
      bioequivalence metrics. It is easier to construct methods that do not require the
      administration of an IV, oral solution, or IR reference dose. A variety of
      convolution-based IVIVC models and modeling strategies are possible depending on
      the relationship between in vivo and in vitro release, the existence of nonlinear
      absorption or presystemic biotransformation, and the in vivo study design. The
      simplest approach is applicable to the case where the in vitro release rate
      equals the in vivo release (or absorption) rate and the study design includes the
      administration of an IV, oral solution, or IR dose. That basic convolution-based
      method can be extended to adjust for differences between the in vitro and in vivo
      release rates. This is accomplished by formally modeling those differences.
      Potential models include time-scaling and convolution. The extent of drug
      absorption may sometimes depend upon the release rate. This may be due to
      phenomena such as saturable presystemic biotransformation or truncated absorption
      due to intestinal transit past the sites of absorption. The relationship between
      the in vitro release rate and extent of absorption may be modeled empirically or
      mechanistically. Such models may be coupled with convolution to construct an
      overall IVIVC model for the relationship between in vitro release and plasma drug
      concentrations. It is also possible to apply convolution-based IVIVC models to
      study designs in which no IV, oral solution, or IR dose has been administered.
      Details of the various modeling approaches listed above are presented. Selected
      approaches are illustrated by examples of their application to real data.

PMID- 9269484
TI  - Approaches to IVIVR modelling and statistical analysis.

PMID- 9269485
TI  - Validation of in vitro-in vivo correlation models.

PMID- 9269486
TI  - Examples of developing in vitro-in vivo relationships.

PMID- 9269487
TI  - The biopharmaceutic drug classification and drugs administered in extended
      release (ER) formulations.
AB  - A biopharmaceutic drug classification scheme for correlating the in-vitro drug
      product dissolution and in-vivo bioavailability for IR products was proposed by
      Amidon et al (1995). The classification arose from drug dissolution and
      absorption models which identified the key parameters controlling drug absorption
      as the dimensionless numbers; the Absorption number (A(n)), the Dissolution
      number (Dn) and the Dose number (D(o)). This led to a biopharmaceutic
      classification of drugs into four groups, the establishment of a basis for
      determining the conditions under which in-vitro-in-vivo (IVIV) correlation's are
      expected and the use of the classification to set drug bioavailability standards
      for IR products. These developments raise the issue of whether the
      biopharmaceutic classification has relevance to ER products. In contrast to IR
      products, drugs selected for ER products should have good gastrointestinal (GI)
      permeability and an extended site of absorption. However their permeability(Papp)
      may change depending on the site. Solubility(Cs), effective fluid volume and
      hence D(o) may also vary with site. Of particular relevance to both permeability
      and solubility is the degree of ionization of the drug. Residence time at each
      site, pH changes and the potential for drug degradation at different sites, the
      latter resulting in a restricted absorption window, will influence the time frame
      over which an IVIV relationship is possible. Of the drugs available in ER dosage
      forms approximately 63% are bases, 15% acids and the remainder either unionizable
      or small inorganic ions. Acidic drugs will tend to have lower solubility's high
      up in the gastrointestinal tract (GIT), with solubility increasing down the GIT.
      In contrast with increased ionization permeability should fall. Thus with acids,
      as the dosage form moves to a more alkaline environment down the GIT, absorption
      may change from dissolution control to membrane control depending on the pK.a of
      the drug. In contrast bases will loose solubility with transit down the GIT, but
      become more permeable; absorption becoming more dissolution/release controlled or
      in extreme cases solubility controlled in the latter stages of the absorption
      phase. In the light of the above considerations a modified biopharmaceutic
      classification is proposed for ER products.

PMID- 9269488
TI  - Investigating in vitro drug release mechanisms inside dosage forms. Monitoring
      liquid ingress in HPMC hydrophilic matrices using confocal microscopy.

PMID- 9269489
TI  - Determination of critical manufacturing and formulation variables for a
      hydrophilic matrix tablet formulation using an in vitro discriminatory
      dissolution method.

PMID- 9269490
TI  - Artificial neural network based in vitro-in vivo correlations.

PMID- 9269491
TI  - Setting dissolution specifications for modified-release dosage forms.
AB  - Dissolution specifications are used for quality assurance and may also serve as a
      surrogate for in vivo bioavailability. These limits can guide formulation
      development and eliminate the need for bioavailability studies for scale up and
      post approval changes. Several methods for setting dissolution specifications
      have been reviewed in this chapter. A summary of the advantages and disadvantages
      for each method can be found in Table 1. When choosing a method for setting
      dissolution specifications, it is important to 1) have a discriminating
      dissolution system, 2) incorporate in vivo data, 3) include intersubject
      variability, and 4) predict plasma concentration-time profiles. Predicting plasma
      concentration curves allows one to see how the change in formulation or
      dissolution limits perform in vivo. Dissolution specifications should be set so
      that all formulations that have dissolution profiles within the limits of the
      specifications are bioequivalent. This can be assured if the boundaries are
      tested for bioequivalence. Minimally, the formulations that have dissolution
      profiles within the limits of the specifications should be bioequivalent to the
      pivotal batch. A population prediction of the plasma concentration-time profiles
      for the upper and lower limit would incorporate the true intersubject variability
      for the formulation.

PMID- 9269492
TI  - Review of methodologies for the comparison of dissolution profile data.

PMID- 9269493
TI  - Assessing whether controlled release products with differing in vitro dissolution
      rates have the same in vivo-in vitro relationship.

PMID- 9269495
TI  - In vitro-in vivo relationships of several "immediate" release tablets containing
      a low permeability drug.
AB  - The objective of this work was to gain insight into the biopharmaceutical
      performance of four different but bioequivalent ranitidine hydrochloride tablet
      formulations. This analysis employed a recently described method1 to relate in
      vitro and in vivo data and aimed to facilitate an understanding of oral drug
      product performance. For each ranitidine formulation, dissolution was performed
      using the USP procedure. A four-way, single dose bioequivalence study (n = 14)
      was performed. The fraction of the total amount of dose absorbed at each plasma
      sample time was determined by the Wagner-Nelson method. Equation 1 (see below)
      was fitted to the in vitro vs. in vivo data. For all four formulations, this
      analysis suggests absorption was permeation-rate limited, where ranitidine
      exhibited a low permeation rate constant of 0.01/min.

PMID- 9269494
TI  - Comparison of methodologies for evaluating regional intestinal permeability.

PMID- 9269496
TI  - Nonlinear in vitro-in vivo correlations.

PMID- 9269497
TI  - Use of nonlinear mixed effects modelling in the development of in vitro-in vivo
      correlations.

PMID- 9269498
TI  - The development of a novel in vitro discriminatory dissolution method for a class
      I drug in a matrix tablet formulation.

PMID- 9269500
TI  - Development of in vitro-in vivo correlations using various artificial neural
      network configurations.

PMID- 9269499
TI  - In vivo-in vitro evaluation of the impact of accelerated stability conditions on
      a hydrophilic matrix tablet.

PMID- 9269501
TI  - Impact of IVIVR on product development.

PMID- 9269502
TI  - The role of in vitro-in vivo correlations (IVIVC) to regulatory agencies.

PMID- 9269503
TI  - Draft guidance for industry extended-release solid oral dosage forms.
      Development, evaluation and application of in vitro-in vivo correlations.

PMID- 9269504
TI  - Issues important to in vitro-in vivo correlation. IVIVR Workshop open discussion.

PMID- 9269505
TI  - Sensitization to Olea europaea: geographical differences and discrepancies.
AB  - Thirty eight patients from two geographical areas of Spain, with great
      differences in Olea europaea pollen counts were studied to investigate their in
      vivo and in vitro immune response to this pollen as a consequence of their
      different environmental allergen exposure. They were distributed in two groups
      (13 from Madrid, and 25 from Jaen). Skin sensitivity was assessed by a prick-test
      dose-response bioassay using serial dilutions of a biologically standardized
      allergen extract of O. europaea. Serological immune response was evaluated
      measuring specific antibody levels (IgE, IgG, IgG1 and IgG4). The patients from
      Jaen, who have a higher exposure to olive pollen, had higher levels of specific
      antibodies but significantly smaller wheal sizes than a similar patient
      population form the Madrid area, where olive pollen is not so copious. There is a
      great discrepancy between the results of skin prick tests (low cutaneous
      reactivity associated with high allergenic environmental load) and the levels of
      specific IgE to the olive pollen. While the level of specific antibodies
      increases with the allergenic load, the capacity to release mediators seems to be
      decreased, at least in the skin. Further studies are needed to evaluate if these
      findings also occur in other target organs with appropriate challenge tests
      (conjunctival, nasal and bronchial). This pattern should be studied with other
      allergens in large patient populations.

PMID- 9269506
TI  - Preseasonal specific immunotherapy with modified Phleum pratense allergenic
      extracts: tolerability and effects.
AB  - The preparation of chemically modified allergens, with a reduced IgE binding
      capacity (responsible for side effects with traditional immunotherapy) but with
      the same or greater immunogenic activity, is one of the paths followed to obtain
      better results with specific immunotherapy (IT). The aim of the study was to
      evaluate the tolerability and effects of an extract Phleum pratense, modified
      with glutaraldehyde and absorbed on aluminium hydroxide, in controlling the
      seasonal symptomatology induced by grass pollen in a group of 10 monosensitized
      patients, compared to a group of 10 similar patients not treated with specific IT
      but with drugs alone. The monitoring parameters were: 1) Clinical: a)
      symptomatology after specific conjunctival provocation test (pre and post
      seasonal) and during the natural exposure to the allergen b) drug consumption. 2)
      Immunological (peripheral blood eosinophils, total and specific IgE, total
      specific IgG). 3) Cytological, before, during and after the pollen season.
      CONCLUSIONS: In subjects treated with specific IT a) both the overall
      symptomatology and the drug consumption resulted significantly reduced compared
      to the controls (p = 0.045); b) the phlogistic infiltrate showed a tendency to
      decrease during the pollen season; c) the peripheral blood eosinophils, total and
      specific IgE and IgG did not show any significant variation compared to the
      controls; d) no systemic reactions occurred and there were only two slight local
      reactions.

PMID- 9269507
TI  - Breast cancer associated mucin: a review.
AB  - Breast mucins are expressed by malignant epithelial cells and they elicit an
      immune reaction. The up-regulation of mucin expression is association with tumour
      invasion, this mucin called MUC-1 reduces the cell-cell interaction facilitating
      cell detachment. The MUC-1 gene product, known as polymorphic epithelial mucin is
      a transmembrane high molecular weight glycoprotein. The molecule of MUC-1 has a
      central polypeptidic core with a carbohydrate linked in O-linkage to serines and
      threonines. The carbohydrate side chain epitope of MUC-1 molecule produced by
      breast cancer cells is heavily sialylated, giving their physical properties and
      increasing their immunogenicity. The development of monoclonal antibodies (MAb)
      has led to study the MUC-1 in subcellular extracts, tissues and culture
      supernatants from breast cancer and also colorectal carcinoma. The pattern of
      tumour cell staining with labeled MAb varies according with the grade of
      malignancy; these MAb bind either to peptide sequence and/or to the glycosylated
      epitopes. MUC-1 has a clinical relevance because serum concentrations may be
      useful for monitoring the response to therapy and progress of disease. MUC-1
      epitope masking has been described since specific antibodies can combine with
      them forming immune complexes. Finally, mucins have been considered to develop
      vaccines against cancer, targeting specific carbohydrate and mucin epitopes.

PMID- 9269508
TI  - Bronchial hyperreactivity and immunoglobulin E in Behcet's disease.
AB  - Behcet's disease in a multisystem panvasculitis of unknown etiology. Pulmonary
      manifestations are rare, and there is no specific test to establish the
      inflammation for the precise differentiation between the active and inactive
      cases. Bronchial hyperreactivity (BHR) measured by methacholine challenge test
      and serum total IgE concentrations were investigated in 31 patients who were
      followed at Behcet's Center in hospital clinic and ten healthy controls. The
      patients studied had no evidence of neither any pulmonary disease-both allergic
      and nonallergic-nor family history of atopy. In 14 patients (45.16%) with active
      lesions mean IgE levels were higher than inactive group, 156.43 +/- 381.14 kU/L
      and 94.42 +/- 147.55 kU/L respectively (p > 0.05). We found high total IgE levels
      in eight patients (25.81%) with BD, though they were unrelated to disease
      activity. In our study, BHR related with Behcet's chronicity were also found to
      be positive in eight patients (25.81%). Mean time elapsed since the first
      diagnosis of the disease in patients with positive BHR was (11.13 +/- 3.72 years)
      significantly longer than inactive group (7.10 +/- 4.49 years) (p < 0.05). No
      correlation was found between BHR and serum IgE levels in patients with clinical
      symptoms. Therefore, we suggest that BHR may probably reflects nonspecific
      inflammation which is seen in BD, but cannot be regarded as a specific marker.

PMID- 9269509
TI  - Interleukin-7 modulates CD23 and HLA-DR expression on CD4+ T cells and promotes a
      Th-2 type citokine profile.
AB  - The expression of CD23 on PHA-activated human PBT (peripheral blood T) cells of
      healthy donors was investigated. It appears that CD23 is expressed solely on
      activated CD4+ T cells. Cytofluorotometric analysis revealed that 6% of PHA
      activated CD4+ T cells expressed CD23, while unstimulated CD4+ T cells express no
      detectable CD23. The addition of IL-7 (1000 U/ml) to activated CD4+ T cells
      resulted in a marked augmentation of CD23 expression (29%). CD23 expression was
      blocked by M20 and M26 mAbs, but no reduction was detected by anti-IL-2R (CD25)
      mAb. This suggests that IL-7 has a specific regulatory effect on CD23 expression
      independent of IL-2. Northern Blot analysis showed a marked increase of CD23 mRNA
      detected in PHA-activated CD4+ T cells plus IL-7. IL-7 was also able to
      upregulate the expression of HLA-DR on activated CD4+ T cells. Optimal HLA-DR and
      CD23 induction by IL-7 occurred at 48 and 72 h of culture. The addition of CHX
      revealed that the induction of CD23 and HLA-DR by IL-7 required intact protein
      synthesis. Furthermore, PHA activated CD4+ T cells cultured in the presence of IL
      7 are polarized to a Th-2 pattern of cytokine production.

PMID- 9269510
TI  - Nasal hypersensitivity and recurrent adenoids disease.
AB  - Authors studied nasal hypersensitivity (NH) behaviour on 41 subjects suffering
      from recurrent adenoids disease during their paediatric age. All subjects
      underwent clinical history, ENT examination, skin-test, RAST and non-specific
      nasal provocation test with histamine and assessment of the amount of sneezes.
      The results showed a familial transmission of the NH in 53.6% of cases, a
      hypogammaglobulinemia in 14.6% of cases. NH was present in 57% of subjects, much
      more with higher number of phlogosis, with higher possibility of familial
      transmission and with premature socialisation. These data showed a strict
      correlation between NH and recurrent adenoids disease. This NH didn't reduce in
      subjects undergone adenoidectomy and with time it conditioned the answer of the
      whole airways which could be noticed also in adulthood subjects. The presence of
      this NH had remarkable significance for diagnosis and therapeutic behaviour.

PMID- 9269511
TI  - Atopic dermatitis today.
AB  - This review focuses on recent literature regarding atopic dermatitis (AD). New
      insights in epidemiology, diagnostic criteria, quality of life measures,
      provocative factors, patophysiology and therapy will be highlighted. New
      diagnostic criteria for AD set by the UK working party allow easier epidemiologic
      studies to cope with this increasingly prevalent disease. Immunomodulating
      therapy with cyclosporine holds promise in the treatment of refractory AD.

PMID- 9269513
TI  - Report links appetite suppressants with heart disease. FDA encourages reporting
      of like events.

PMID- 9269512
TI  - Biosynthesis inhibitors for leukotrienes in bronchial asthma.
AB  - This article reviews the literature on the effects of leukotrienes in asthma. In
      particular, the ability of recently developed synthesis inhibitors to attenuate
      the asthma causing effects of leukotrienes is examined. MEDLINE (1966-1996),
      EMBASE (Excerpta Medica; 1974-1996), and other biomedical and drug directory
      databases were searched to identify English-language articles (basic science,
      clinical trial research, and review articles) and abstracts of conference
      proceedings on biosynthesis inhibitors for leukotrienes and related terms.
      Leukotrienes are endogenous molecules formed by the breakdown of a membrane
      constituent, arachidonic acid, via the 5-Lipoxygenase enzyme pathway. This
      pathway ultimately produces several species of leukotrienes with various biologic
      activities, including generalized inflammatory effects associated with asthma:
      increased vascular permeability, enhanced mucous production, and decreased
      mucociliary transport. The biosynthesis inhibitors for leukotrienes attenuated
      the response to inhaled leukotrienes and allergen challenges (MK-0591; MK-886; AA
      681; A-64077; ZD-2138). These agents produced beneficial effects in cold,
      exercise (A-64077) and aspirin-induced asthma (A-64077; ZD-2138), as well as
      clinical asthma. Many of these medications appear to be effective in the
      treatment of asthma (BAYX-1005; MK-0591; MK-886; AA-681; A-64077; ZD-2138; U
      60257; FR-110302; BI-6239; A-78773; ABT-761; L-746530; L-699333; ZM-230487).
      Further clinical research is needed to determine which patients would benefit
      most from their use.

PMID- 9269514
TI  - Imported products ease i.v. multivitamin shortage. Patients suffer serious
      effects of thiamine deficiency.

PMID- 9269515
TI  - Cerivastatin approval expands HMG-CoA reductase inhibitor choices.

PMID- 9269516
TI  - Inhouse clinical training program for staff pharmacists.

PMID- 9269517
TI  - American pharmacy in the twentieth century.

PMID- 9269518
TI  - Joseph A. Oddis: influences and achievements.

PMID- 9269519
TI  - Harvey A. K. Whitney Lecture. Letters from the edge.

PMID- 9269520
TI  - Stability of omeprazole in an extemporaneously prepared oral liquid.
AB  - The stability of omeprazole 2 mg/mL. in an extemporaneously prepared oral liquid
      was studied. The contents of five 20-mg omeprazole capsules were mixed with 50 mL
      of 8.4% sodium bicarbonate solution in a Luer-Lok syringe. Three vials of this
      liquid were prepared for storage at 24, 5, and -20 degrees C. A 3-mL. sample of
      each was taken initially and on days 1, 2, 3, 4, 6, 8, 10, 12, 14, 18, 22, 26,
      and 30 and assayed by high-performance liquid chromatography. The liquids stored
      at 5 degrees C and at -20 degrees C did not change color during the study period,
      but the color of the liquid stored at 24 degrees C changed from white to brown.
      There were no significant changes in the omeprazole concentrations of the liquids
      stored at 5 and -20 degrees C during the study period, but the omeprazole
      concentration of the liquid stored at 24 degrees C was < 90% of the initial
      concentration on day 18. Omeprazole 2 mg/mL in an oral liquid compounded
      extemporaneously from capsules and sodium bicarbonate injection was stable for up
      to 14 days at 24 degrees C and for up to 30 days at 5 and -20 degrees C.

PMID- 9269521
TI  - Development of a patient-focused, interdisciplinary antimicrobial management
      program involving staff pharmacists.

PMID- 9269522
TI  - Development of algorithms for treating patients in the intensive care unit.

PMID- 9269524
TI  - Order form for restricting vancomycin prescribing.

PMID- 9269523
TI  - Precipitation of fluorouracil in elastomeric infusers with a polyisoprene
      reservoir and in polypropylene syringes with an elastomeric joint.

PMID- 9269525
TI  - Computer program for tracking incidence of intravascular-device-related
      infections in patients receiving parenteral nutrition.

PMID- 9269526
TI  - Neurotrophic factors are required by mature sympathetic neurons for survival,
      transmission and connectivity.
AB  - 1. Two neuronal growth factors, nerve growth factor (NGF) and neurotrophin 3
      (NT3), have been studied for their action on the developing and mature
      sympathetic nervous system. 2. Antibodies to each factor have proved useful as
      reagents for the detection and quantification of NGF and NT3. They have also
      proved valuable in uncovering the functional roles of each factor by their
      ability to neutralize the endogenous molecules. 3. Nerve growth factor acts on
      postnatal neurons to control neurotransmission, connectivity and survival. Like
      NGF, NT3 is synthesized by effector tissues and is retrogradely transported by
      post-ganglionic neurons to prevent cell death. However, the two factors have been
      shown to have quite distinct functions in mature neurons, indicating the
      existence of different signalling pathways. This differential action extends to
      secondary influences on satellite glia. 4. Pathological consequences result from
      excessive growth factor synthesis leading, in the hypertensive rat, to
      hyperinnervation and elevated blood pressure. Satellite glial cell synthesis of
      the factors and their receptors following peripheral nerve damage appears to be
      responsible for the establishment of inappropriate neuronal connections between
      sympathetic nerve terminals and sensory somata. 5. It is concluded that these
      potent factors control, by both coincident and independent mechanisms,
      sympathetic neuronal function throughout the life of the animal.

PMID- 9269527
TI  - Determinants of the kinetics of very low-density lipoprotein apolipoprotein B-100
      in non-obese men.
AB  - 1. Apolipoprotein B-100 (ApoB) is the principal structural and functional protein
      of the pro-atherogenic lipoproteins. Elevated plasma apoB is an independent risk
      factor for coronary artery disease. In the present study we aimed to assess the
      factors that determine the kinetics of apoB in the very low-density lipoprotein
      (VLDL) in healthy men. 2. We studied 17 non-obese men who were consuming an ad
      libitum diet and had the following characteristics: mean (+/-SD) age 45.5 +/- 9.7
      years, body mass index (BMI) 25.1 +/- 1.4 kg/m2, waist:hip ratio 0.91 +/- 0.04,
      serum cholesterol 5.2 +/- 0.6 mmol/L, triglycerides 1.08 +/- 0.53 mmol/L and high
      density lipoprotein-cholesterol 1.24 +/- 0.31 mmol/L. Daily dietary intake was as
      follows: total fat 76 +/- 26 g, carbohydrate 238 +/- 67 g, protein 103 +/- 33 g
      and alcohol 20 +/- 16 g. 3. The kinetics of VLDL ApoB were studied using a
      primed, constant infusion (1 mg/kg per h) of 1-[13C]-leucine over 8 h with
      measurement of isotopic enrichment of ApoB using gas chromatography/mass
      spectrometry. The fractional turnover rate of VLDL ApoB was estimated using a
      monoexponential function. The mean (+/-SD) absolute hepatic secretion rate (ASR)
      of ApoB was 8.5 +/- 4.6 mg/kg per day and the fractional catabolic rate (FCR) was
      7.9 +/- 5.6 pools/day. The ASR was significantly correlated with the waist:hip
      ratio (r = 0.60; P = 0.04), but not with age, BMI, weight or nutrient intake. The
      FCR was significantly and inversely correlated with plasma triglycerides (r = 
      0.53; P = 0.03) and alcohol intake (r = -0.48; P = 0.05). 4. In conclusion, the
      hepatic secretion of VLDL ApoB in nonobese, healthy men is primarily determined
      by the waist:hip ratio, a measure of visceral fat. This is consistent with the
      hypothesis that the rate of lipid substrate supply in the liver regulates the
      output of ApoB. The fractional catabolism of VLDL ApoB may, however, be inversely
      related to alcohol intake and appears to determine the plasma concentration of
      triglycerides.

PMID- 9269528
TI  - Human monocytes maintained in culture acquire functional responsiveness to
      platelet-activating factor that is independent of increases in protein tyrosine
      phosphorylation.
AB  - 1. Acute (day 0) stimulation with platelet-activating factor (PAF) did not elicit
      superoxide anion (O2-) generation from adherent monocytes. However, by day 2 of
      culture, PAF induced an increase in O2- generation that was inhibited by
      pretreatment with the PAF receptor antagonist WEB 2086. 2. The lack of effect of
      PAF on O2- generation was not due to the absence of receptors, as PAF stimulated
      an increase in tyrosine phosphorylation and intracellular calcium ([Ca2+]i) on
      both days 0 and 2 of culture. 3. Pretreatment with the protein tyrosine kinase
      inhibitor methyl 2,5-dihydroxycinnamate inhibited PAF-induced tyrosine
      phosphorylation; however, this inhibitor failed to inhibit PAF-induced O2-
      generation. In contrast, pretreatment with the protein kinase C inhibitor
      staurosporine had no effect on PAF-induced tyrosine phosphorylation, but did
      inhibit PAF-induced O2- generation. 4. These results indicate that monocytes
      maintained in culture acquire a functional response to PAF through a mechanism
      that appears to be independent of PAF receptor expression, coupling to increases
      in [Ca2+]i or tyrosine phosphorylation.

PMID- 9269529
TI  - Effects of veratridine on the action potentials and contractility of right and
      left ventricles from normo- and hypertensive rats.
AB  - 1. We have studied the effects of prolonging the opening of sodium channels with
      veratridine on the action potentials (AP) and contractility of isolated right and
      left ventricles of Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats
      (SHR). It was examined whether the effects of veratridine were altered in the SHR
      right ventricle in the absence of hypertrophy. The main aim of the present study
      was to test the hypothesis that the effects of veratridine were altered in the
      SHR left ventricle in the presence of hypertrophy. 2. The tail-cuff pressures of
      14- and 22-week-old, but not 5-week-old, SHR were greater than those of the WKY
      rat. At 14 weeks of age of SHR left, but not right, ventricle had developed
      hypertension-associated hypertrophy. 3. The AP and contractions and the ability
      of veratridine to prolong the AP and act as a positive inotrope were similar in
      the right ventricles from 22-week-old WKY rats and SHR. The effects of
      veratridine and the AP and contractions of left ventricles of 5-, 14- and 22-week
      old WKY rats and of 5- and 14-week-old SHR were also similar. 4. The AP of the
      left ventricles of 22-week-old SHR were prolonged by 3 ms at the action potential
      duration (APD)50 and APD90 levels. The contractions to cardiac stimulation and
      the maximum combined force responses to cardiac stimulation and isoprenaline were
      reduced in the left ventricles of 22-week-old SHR compared with WKY rats and
      younger SHR. 5. The effectiveness of veratridine in prolonging the AP and
      augmenting the contractions to cardiac stimulation was reduced in the
      hypertrophied left ventricle of 22-week-old, but not 14-week-old, SHR. 6. In
      summary, the response to prolonging the opening of sodium channels with
      veratridine is not altered in the SHR right ventricle. However, in left
      ventricles of the hypertrophied 22-week-old, but not 14-week-old, SHR the effects
      of veratridine are reduced and this demonstrates that the response to prolonging
      the opening of sodium channels is changed in persistent hypertension-associated
      hypertrophy.

PMID- 9269530
TI  - Role of nitric oxide in the control of glomerular microcirculation.
AB  - 1. Nitric oxide (NO) plays an important role in the control of glomerular
      haemodynamics and is synthesized from the amino acid L-arginine by a family of
      enzymes, NO synthase (NOS). 2. Nitric oxide synthase is present in the
      endothelium and also in the macula densa, a plaque of specialized tubular
      epithelial cells. Endothelial NOS is known to be stimulated by shear stress and
      hormones, while the factor that regulates the activity of macula densa NOS
      remains undefined. 3. Studies with the in vitro microperfusion of glomerular
      arterioles have shown that the constriction of afferent arterioles (Af-Art)
      induced by myogenic responses and angiotensin II (AngII) is stronger in the
      absence rather than in the presence of luminal flow. Furthermore, endothelial
      disruption or NOS inhibition abolishes such differences, suggesting that flow
      through the lumen stimulates the endothelium to synthesize and release NO, which
      in turn attenuates both the myogenic response and the action of AngII in the Af
      Art. 4. In contrast, NOS inhibitors have no effect on efferent arteriolar (Ef
      Art) constriction induced by AngII. 5. In preparations in which Af-Art and the
      macula densa are simultaneously microperfused, selective inhibition of macula
      densa NOS has been shown to augment Af-Art constriction when the NaCl
      concentration at the macula densa is high, suggesting that the macula densa
      produces NO, which in turn modulates tubuloglomerular feedback. 6. Thus, the
      differential actions of NO in the Af-Art, Ef-Art and the macula densa may be
      important in the control of glomerular haemodynamics under various physiological
      and pathological conditions.

PMID- 9269531
TI  - Role of nitric oxide in tubuloglomerular feedback: effects of dietary salt.
AB  - 1. The tubuloglomerular feedback (TGF) response operates primarily by
      vasoconstriction of the afferent arteriole and a fall in glomerular capillary
      pressure (PGC) and single-nephron glomerular filtration rate (SNGFR) during
      increased NaCl reabsorption in the macula densa (MD). Numerous studies have
      suggested that nitric oxide (NO) is synthesized by the MD and acts to suppress
      TGF. As a high-salt (HS) diet has been found to blunt TGF, we tested the effects
      of salt intake on NO-dependent changes in TGF. 2. In the first series of
      experiments, values of SNGFR were contrasted from samples of tubular fluid taken
      from the proximal tubule (PT; MD delivery interrupted) and the distal tubule DT;
      MD delivery intact). Compared with HS rats, the difference between PT and DT
      values of SNGFR was increased in low-salt (LS) diet rats (4.3 +/- 0.4 vs 10.3 +/-
      1.2 nL/min, respectively; P < 0.001). Intravenous infusion of NG-monomethyl-L
      arginine (L-NMMA), in pressor doses increased the difference between PT and DT
      values of SNGFR of HS rats (4.3 +/- 0.4 vs 9.5 +/- 1.2 nL/min before and during L
      NMMA, respectively; P < 0.001) without significantly affecting values in LS rats
      (10.3 +/- 1.2 vs 12.3 +/- 1.4 nL/min before and during L-NMMA, respectively; NS).
      3. A second series of experiments assessed TGF responses directly. Changes in
      stop-flow pressure (PSF; an index of PGC) were measured in response to graded
      perfusion of the loop of Henle (LH) with artificial tubular fluid. Loop perfusion
      with 10(-3) mol/L L-NMMA did not affect the PSF responses of LS rats but did
      reduce (P < 0.01) the PSF of HS rats during perfusion at 20 nL/min (-1.5 +/- 0.4
      mmHg; P < 0.01), 30 nL/min (-1.8 +/- 0.5 mmHg; P < 0.01) and 40 nL/min (-2.2 +/-
      0.5 mmHg; P < 0.001). 4. We conclude that the TGF response is increased by
      suppression of NOS activity during HS but not LS intake.

PMID- 9269532
TI  - Role of nitric oxide in the control of the renal medullary circulation.
AB  - 1. Nitric oxide (NO) has been implicated as an important controller in the short-
      and long-term regulation of arterial pressure. Studies performed in our
      laboratory have demonstrated that chronic intravenous administration of the NO
      synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) selectively
      decreases renal medullary blood flow, causes sodium and water retention and leads
      to hypertension. 2. To determine the importance of the renal medullary effects in
      this model of hypertension, further studies were conducted to examine the
      influence of selective stimulation or inhibition of renal medullary NO on whole
      kidney function and cardiovascular homeostasis. With the use of a unique catheter
      to directly infuse into the renal medullary interstitial space, stimulation
      (bradykinin or acetylcholine) or inhibition (L-NAME) of renal medullary NO
      selectively increased or decreased renal medullary blood flow. 3. The changes in
      medullary flow in these experiments were associated with parallel changes in
      sodium and water excretion independent of alterations in renal cortical blood
      flow or glomerular filtration rate. 4. Studies were then undertaken to examine
      the long-term effects of selective NO inhibition in the renal medulla on
      cardiovascular homeostasis. Chronic infusion of L-NAME directly into the renal
      medullary interstitial space of uninephrectomized Sprague-Dawley rats led to a
      selective decrease in renal medullary blood flow that was sustained throughout
      the 5 day L-NAME infusion period. The decrease in medullary blood flow was
      associated with retention of sodium and the development of hypertension and the
      effects were reversible. 5. The data reviewed indicate that NO in the renal
      medulla has a powerful influence on fluid and electrolyte homeostasis and the
      control of blood pressure.

PMID- 9269533
TI  - Actions of nitric oxide on renal epithelial transport.
AB  - 1. In vivo studies have demonstrated that nitric oxide (NO) induces natriuresis.
      Nitric oxide-induced natriuresis occurs independently of changes in renal
      perfusion pressure, indicating that it is the result of a tubular effect of NO.
      2. In support of this hypothesis investigators have shown that NO inhibits both
      Na(+)-H+ exchange and Na+/K(+)-ATPase activity in the proximal tubule. In the
      collecting duct, NO has been shown to decrease sodium flux with no effect on
      Na+/K(+)-ATPase activity. 3. Thus, direct examination of the actions of NO have
      shown that NO can inhibit sodium transport in the nephron, which may account for
      the natriuresis observed in vivo.

PMID- 9269534
TI  - Nitric oxide in the mediation of pressure natriuresis.
AB  - 1. Recent studies have indicated that nitric oxide (NO) production in the kidney
      contributes to the regulation of renal haemodynamics and excretory function.
      Inhibition of nitric oxide synthase (NOS) reduces renal blood flow by
      approximately 25% and markedly reduces sodium excretion without reductions in
      filtered load. In particular, inhibition of NO synthesis markedly suppresses the
      slope of the arterial pressure-mediated response in sodium excretion. 2. Further
      studies have shown that constant intrarenal infusion of a NO donor in dogs
      treated with a NOS inhibitor produced diuretic and natriuretic responses but
      failed to restore the slope of the pressure-induced natriuretic response. These
      data indicate that an alteration in intrarenal NO activity, rather than the
      simple presence of NO during changes in arterial pressure is required for full
      expression of pressure natriuretic responses. 3. In support of the hypothesis
      that NO is involved in the mediation of pressure natriuresis, we also recently
      demonstrated a direct relationship between changes in arterial pressure and
      urinary excretion rate of sodium as well as nitrate and nitrite (a marker for
      endogenous NO activity) in the presence of efficient autoregulation of cortical
      and medullary blood flow. 4. The direct inhibitory actions of NO on tubular
      sodium reabsorption have also been observed in cultured tubular cells as well as
      isolated, perfused cortical collecting duct segments. 5. Thus, the collective
      data suggest that acute changes in arterial pressure induce changes in intrarenal
      NO production, which may directly alter tubular reabsorptive function to manifest
      the phenomenon of pressure natriuresis.

PMID- 9269535
TI  - Nitric oxide, the kidney and hypertension.
AB  - 1. According to the renal body fluid feedback mechanism for long-term control,
      persistent hypertension can only occur as a result of a reduction in renal sodium
      excretory function or a hypertensive shift in the pressure natriuresis
      relationship. Although an abnormal relationship between renal perfusion pressure
      and renal sodium excretion has been identified in every type of hypertension
      where it has been sought, factors responsible for this effect are still unclear.
      2. Nitric oxide (NO) is produced within the kidney and plays an important role in
      the control of many intrarenal processes that regulate the renal response to
      changes in perfusion pressure and, thus, help determine systemic vascular volume
      and blood pressure. Numerous studies have shown that long-term inhibition of NO
      synthesis results in a chronic hypertensive shift in renal pressure natriuresis.
      3. Recent studies have shown that certain animal models of genetic hypertension
      and forms of human hypertension areas are associated with a decrease in NO
      synthesis. Reductions in NO synthesis reduce renal sodium excretory function, not
      only through direct action on the renal vasculature, but through modulation of
      other vasoconstrictor processes and through direct and indirect alterations in
      tubular sodium transport. 4. The causes and consequences of the disregulation of
      NO in hypertension and other renal disease processes remain an important area of
      investigation.

PMID- 9269536
TI  - Intrarenal localization of nitric oxide synthase isoforms and soluble guanylyl
      cyclase.
AB  - 1. Nitric oxide (NO) plays an important role in the regulation of renal function.
      To date, five isoforms of NO synthase (NOS) and four subunits of soluble guanylyl
      cyclase have been cloned. The kidney contains four isoforms of NOS and all
      subunits of soluble guanylyl cyclase. 2. This review focuses on the intrarenal
      location of the isoforms of NOS and the subunits of soluble guanylyl cyclase.

PMID- 9269537
TI  - Protein phosphorylation events in exocytosis and endocytosis.
AB  - 1. Exocytosis and endocytosis are the continuous outward and inward vesicular
      transports in a cell that occur constantly for intra- and inter-cellular
      communications. These events are accomplished with the release and uptake of
      chemical messages fundamental in a variety of cellular functions, such as
      neurotransmitter release, hormone secretion and receptor internalization. 2.
      Although the mechanisms underlying these events have not been fully established,
      it is widely accepted that they are largely mediated and controlled by a number
      of effector proteins. These proteins can operate individually and in concert to
      produce specialized machineries in the sequential steps of exocytotic and
      endocytic transports. 3. Protein phosphorylation, the most common covalent
      modification of proteins in cells, has been implicated as playing an important
      role in the regulation of exocytosis and endocytosis. Many proteins involved in
      these processes have been identified to be phosphorylated under certain
      conditions. 4. For instance, synapsin I, myristoylated alanine-rich C kinase
      substrate and dynamin I undergo dynamic phosphorylation and dephosphorylation
      cycles during exocytosis and endocytosis, implying that protein phosphorylation
      regulates the functions of these proteins and, thus, exocytosis and endocytosis.

PMID- 9269538
TI  - Protein kinase C and transmitter release.
AB  - 1. Protein kinase C (PKC) is an important second messenger-activated enzyme. In
      noradrenergic nerves it appears to be tonically activated by diacylglycerol (DAG)
      to facilitate transmitter release and the steps in this involve activation of
      phospholipase C, generation of DAG and activation of PKC. It is suggested that
      the subsequent facilitation of transmitter release is due to the phosphorylation
      of proteins involved in the release process distal to Ca2+ entry, presumably
      those involved in vesicle dynamics. 2. There are differences between central
      noradrenergic neurons and sympathetic nerves. In central neurons PKC appears to
      be tonically active and its inhibition results in a decrease in noradrenaline
      release under most, if not all, conditions. 3. In sympathetic nerves PKC
      inhibitors only decrease transmitter release during high-frequency stimulation
      and not during low-frequency stimulation. At high frequency there is a gradual
      increase in the effect of PKC inhibitors on transmitter release during the first
      15 s of a stimulation train. It is suggested that this is due to a progressive
      rise in intracellular Ca2+ and a consequent activation of PKC. 4. Activation of
      PKC by phorbol esters produces a large enhancement in action potential-evoked
      noradrenaline release in both the central nervous system and in peripheral
      tissues. The structural requirements of the phorbol esters for maximal effect
      suggest that the phorbol esters must access the interior of the nerve terminal to
      activate PKC and the neural membrane acts as a barrier for highly lipophilic
      phorbol esters, thereby reducing their activity. Activation of PKC represents one
      of the most powerful ways to enhance transmitter release and may have therapeutic
      potential.

PMID- 9269539
TI  - Histamine-stimulated phospholipase C signalling in the adrenal chromaffin cell:
      effects on inositol phospholipid metabolism and tyrosine hydroxylase
      phosphorylation.
AB  - 1. The present report gives a detailed account of histamine-stimulated
      phospholipase C (PLC) activity in bovine adrenal chromaffin cells. 2. Histamine
      activation of H1 receptors stimulates PLC with a biphasic sensitivity to
      extracellular Ca2+. The initial response (the first 15 s stimulation) was not
      reduced by the removal of extracellular Ca2+, whereas the maintenance of PLC
      activity beyond this time required Ca2+ influx. 3. Phospholipase C activity in
      response to a 10 min incubation with histamine was inhibited by La3+ (3 mmol/L)
      or SKF96365 (10 mumol/L). Nifedipine (10 mumol/L), but not omega-agatoxin IVA
      (100 nmol/L) or omega-conotoxin GVIA (300 nmol/L), produced a partial inhibition
      of PLC activity. The response was also partially inhibited by a reduction in the
      extracellular Cl- concentration (40 mmol/L) or by the inclusion of the Cl-
      channel blocker N-phenylanthranilic acid (300 mumol/L). 4. Kinetic analysis of
      the rate of turnover of the various inositol phosphate isomers in response to
      histamine suggested that the inositol monophosphates were being produced from a
      source in addition to inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) metabolism.
      This conclusion was supported by the differential action of pertussis toxin and
      neomycin on Ins(1,4,5)P3 formation compared with inositol monophosphate
      formation. 5. We have attempted to identify a defined role for the intracellular
      Ca2+ mobilized in these cells in response to histamine. After short incubations
      (up to 3 min), histamine was able to regulate the site-specific phosphorylation
      of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis.
      This observation has important implications for a possible role for the PLC
      signalling pathway in controlling the rate of catecholamine biosynthesis.

PMID- 9269540
TI  - Competition by second messenger systems for receptor interaction and activation:
      implications for tissue-specific responses and disease therapy.
AB  - 1. At any one instant, most receptors are now recognized to be able to stimulate
      multiple signal transduction pathways in a cell when activated by an appropriate
      hormone. These different signalling pathways appear to allow for distinct
      cellular responses, such as cell proliferation, differentiation, and shape
      change. 2. In addition, many different types of cell will possess the same type
      of receptor. Therefore, for a hormone to be able to transmit differential signals
      to the various cell types able to respond to it, cells must discriminate the
      stimulus at some point. Such discrimination would seem to be an absolute
      requirement to allow a tissue-specific response to an identical initial stimulus.
      In theory, this specificity could occur at many points in the receptor signal
      transduction cascade, including cytosolic receptor coupling systems and
      tissue/cell-specific responsive genes. 3. The present paper summarizes our work
      and that of others which has determined some of the coupling systems of G-protein
      coupled receptors and tyrosine kinase receptors and how these systems may be
      interacting. 4. In addition to these theoretical considerations, a potential
      therapeutic strategy underlies the ability of receptors to couple to more than
      one signal transduction system. If a response to a hormone were, for example,
      either cell proliferation or cell morphological change or differentiation and
      separate receptor-coupled signalling systems were responsible for these effects,
      pharmacological intervention may allow the transfer from one signalling system to
      another. If such a change allowed a permanent change to the differentiated
      phenotype, this could potentially form the basis of a signal-based cancer
      therapy.

PMID- 9269541
TI  - G(o)2 and Gi3 proteins mediate the action of somatostatin on membrane Ca2+ and K+
      currents in ovine pituitary somatotrophs.
AB  - 1. Growth hormone (GH) secretion from the anterior pituitary gland is mainly
      regulated by hypothalamic GH-releasing hormone (GHRH) and somatostatin (SRIF).
      Somatostatin reduces both spontaneous and GHRH-stimulated GH secretion. 2.
      Exocytosis of GH is mainly determined by the intracellular free Ca2+
      concentration ([Ca2+]i), which is regulated by the influx of Ca2+ via membrane
      Ca2+ channels. Somatostatin reduces the influx of Ca2+ through two separate
      mechanisms, namely a direct action on Ca2+ channels and an indirect action on
      membrane potentials through the activation of K+ channels. 3. In the present
      experiments, somatotroph-enriched cells were obtained from the ovine pituitary
      gland by means of collagenase dissociation and Percoll-gradient centrifugation.
      Further identification was based on the effect of SRIF (10 nmol/L) on Ca2+ or K+
      currents. 4. A significant reduction in Ca2+ currents and an increase in K+
      currents was obtained in response to local application of SRIF (10 nmol/L), but
      vehicle application had no effect. The responses of Ca2+ and K+ currents to SRIF
      were reversible after removal of SRIF. 5. Dialysis of GTP-gamma-s (200 mumol/L)
      abolished the recovery phase of K+ current response to SRIF after its removal,
      whereas GDP-beta-s (200 mumol/L) totally blocked the response. Pretreatment of
      the cells with pertussis toxin (100 nmol/L) overnight abolished the Ca2+ current
      response to SRIF. 6. Intracellular dialysis of antibodies to alpha o, alpha i1-3,
      alpha i1-2 and alpha i3 subunits of the G-proteins into cells via whole-cell
      patch-clamp pipettes was confirmed by immunofluorescent staining of the
      antibodies. 7. Dialysis of anti-alpha i1-3 or anti-alpha i3 antibodies
      significantly attenuated the increase in the K+ current in response to 10 nmol/L
      SRIF, whereas neither anti-alpha o nor anti-alpha i1-2 antibodies diminished the
      effect of SRIF on the K+ current. 8. Dialysis of anti-alpha o antibodies
      significantly attenuated the reduction in the Ca2+ current that was obtained upon
      application of 10 nmol/L SRIF. Neither anti-alpha i1-2 nor anti-alpha i3 antibody
      dialysis diminished the effect of SRIF on the Ca2+ current. 9. Dialysis of the
      alpha o common antisense oligonucleotides (ASm) but not the alpha i3 AS
      significantly diminished the inhibitory effect of SRIF on the Ca2+ current. This
      effect of alpha o ASm dialysis occurred at 12 h incubation after dialysis,
      reaching a maximal level at 48 h and partially recovering at 72 h incubation.
      Antisense oligonucleotides specific for alpha o1 (alpha o1 AS) or alpha o2 (alpha
      o2 AS) were dialysed into somatotrophs and only alpha o2 AS significantly
      attenuated the inhibition of SRIF on the Ca2+ current. 10. It is concluded that
      the Gi3 protein mediates the effect of SRIF on the K+ current and that the G(o)2
      protein mediates the effect of SRIF on the Ca2+ current in primary cultured ovine
      somatotrophs.

PMID- 9269542
TI  - The optimal duration of adjuvant tamoxifen treatment for breast cancer remains
      uncertain: randomize into aTTom.

PMID- 9269543
TI  - Where next in the treatment of rectal cancer?

PMID- 9269544
TI  - Prophylactic cranial irradiation in small cell lung cancer (SCLC) makes a
      comeback.

PMID- 9269546
TI  - Radiation dose in Hodgkin's disease: are we overtreating?

PMID- 9269545
TI  - Radiotherapy for painful bone metastases: a systematic review.

PMID- 9269547
TI  - Retreatment of patients with intracranial gliomas by external beam radiotherapy
      and cytotoxic chemotherapy.
AB  - Twenty-one patients with recurrent intracranial gliomas were retreated by
      external beam radiotherapy between 1987 and 1995. Twenty patients received
      cytotoxic chemotherapy involving CCNU as part of their retreatment. Only five of
      the 21 patients had received chemotherapy in combination with the initial
      external beam radiotherapy (RT) prior to recurrence. The different histological
      groups were analysed and the patients divided into two groups; group I (Grade I
      and II gliomas) and group II (Grade III, IV and glioblastoma). The overall median
      survival for all patients was 59 months, with a median survival of 22 months
      after recurrence. For group I and group II patients, the median survival was 26
      months and 13 months after recurrence respectively. It was concluded that some
      highly selected patients with intracranial gliomas can be retreated safely by
      carefully planned external beam RT given to a relatively low dose in order to
      palliate neurological dysfunction and the symptoms of raised intracranial
      pressure, and to reduce steroid dependency. The results strongly suggest that
      recovery does occur after initial RT. Retreatment may possibly improve survival
      in a small proportion of patients. Further studies, including randomized trial
      designs, quality of life assessment, and neurological symptoms indices, would be
      required to determine the quantitative benefit of any such treatment policy. The
      objectives of this study were to determine whether patients received any benefit,
      such as symptom relief and the allowance of steroid withdrawal, after
      retreatment, and whether long term survival could be achieved.

PMID- 9269548
TI  - The natural history and management of Merkel cell carcinoma of the skin: a review
      of 22 patients treated at the Royal Marsden Hospital.
AB  - Merkel cell carcinoma is a rare skin malignancy, which primarily affects the
      elderly. Currently, there is only limited data on the natural history of this
      condition and no consensus on its optimum management. We have reviewed the
      natural history and management of 22 patients with Merkel cell carcinoma, who
      were treated at the Royal Marsden Hospital between 1985 and 1994. The median age
      at diagnosis was 75 years (range 55-96), with the head and neck region being the
      most common site of disease (nine patients: 41%). Seventeen patients (77%)
      presented with skin disease, three (14%) with regional lymphadenopathy and two
      (9%) with metastatic disease. Of the Stage I patients, 41% developed local
      recurrence postoperatively at a median time to relapse of 12 months. Those with
      head and neck disease had the highest risk of local recurrence, which occurred in
      62.5% of this group. Stage I patients also had a high risk of disease
      progression, with 53% developing regional lymphadenopathy or visceral metastases.
      The median survival for all disease stages was 47 months. The treatment of
      unresectable primary or recurrent disease with radiotherapy led to valuable long
      term control in four of nine patients treated. Six courses of chemotherapy were
      administered; one brief complete response was observed, occurring in a patient
      treated with cyclophosphamide, vincristine and doxorubicin. The data in this
      study confirms the predilection for the elderly and the aggressive nature of
      Merkel cell carcinoma, with only four of 17 Stage I patients remaining disease
      free. To clarify the role of adjuvant postoperative radiotherapy and to establish
      the appropriate use of chemotherapy in metastatic spread of this rare malignancy
      will require further studies with multicentre cooperation.

PMID- 9269549
TI  - The content and efficacy of conventional methods of follow-up in neuro-oncology:
      the need for new strategies.
AB  - In a combined retrospective and prospective analysis, we examined the content and
      outcome of conventional follow-up of patients with malignant brain tumours. Most
      consultations consisted of discussion and advice from the clinic doctor or nurse
      in certain well defined areas. Clinical examination, including neurological
      examination, was ineffective at detecting tumour recurrence. All recurrences
      presented with clinical features noted by the patient or by carers prior to the
      clinic attendance. The analysis of content and outcome of conventional outpatient
      consultation suggests that patients with high grade gliomas might be better
      served by methods of follow-up other than routine hospital attendance. There is a
      need to develop new follow-up strategies which are patient orientated and which
      address issues specific to the disease type other than tumour recurrence alone.

PMID- 9269550
TI  - Citrobacter freundii and fatal neutropenic enterocolitis following adjuvant
      chemotherapy for breast cancer.
AB  - Neutropenic enterocolitis is increasingly being recognized as a life-threatening
      complication of chemotherapy, mainly for haematological and lymphoproliferative
      malignancies. It is under-recognized clinically, with the diagnosis often being
      made on post-mortem examination. Although active medical management is generally
      preferred, surgical intervention may be indicated. We report a case of fatal
      neutropenic enterocolitis, secondary to Citrobacter freundii, following adjuvant
      chemotherapy for breast cancer. We also review the literature, examining the
      aetiology, diagnosis and management of this often fatal entity.

PMID- 9269551
TI  - Complete remission of extensive metastatic renal cancer following immunotherapy.
AB  - The authors describe the case history of a 54-year-old female patient, who
      presented with breathlessness, deteriorating general health and a 12 kg weight
      loss due to extensive metastatic renal cancer. Pulmonary emboli complicated the
      presentation. The patient entered a remarkable complete radiological remission by
      18 weeks following the introduction of interleukin-2/alpha-interferon
      immunotherapy. The possibility of immediate nephrectomy or warfarin contributing
      to the augmentation of the effects of the immunotherapy is discussed.

PMID- 9269553
TI  - Spontaneous gas gangrene: an unusual complication of colonic carcinoma.
AB  - Clostridium septicum myonecrosis is an acutely painful and rapidly fatal
      infection occurring in the absence of trauma. Urgent surgery is essential both to
      maximize survival and to provide effective pain control. The majority of patients
      who develop this infection have an underlying malignancy and clinicians involved
      in the care of cancer patients should be aware of this condition. We present a
      case report and summarize the literature to date.

PMID- 9269552
TI  - A durable response to cytarabine in advanced breast cancer.
AB  - Cytarabine is a useful agent in the management of acute leukaemias, but is not
      thought to have activity in solid tumours. We describe the case history of a
      woman with advanced breast cancer, presenting with superior vena cava obstruction
      occurring after radiotherapy and chemotherapy, who had a durable remission
      following inadvertent dosing with cytarabine. A review of the literature reveals
      that this is the first documented case of a meaningful response to cytarabine in
      metastatic breast cancer.

PMID- 9269554
TI  - A patient with classical Kaposi's sarcoma and angiosarcoma: bad luck or a common
      aetiology?
AB  - Classical Kaposi's sarcoma and angiosarcoma are rare malignant tumours arising
      from vascular tissue. However, they have distinct histological features and
      appear also to differ in their epidemiology and pathogenesis. We present the case
      history of a patient in whom both these tumours occurred simultaneously. The
      relationship between these events is discussed in the light of the new virus,
      human herpes virus 8.

PMID- 9269555
TI  - Continuous intrathecal perfusion of methotrexate for carcinomatous meningitis
      with pharmacokinetic studies: two case studies.

PMID- 9269556
TI  - Aggressive primary natural killer cell lymphoma of the caecum: a case report and
      literature review.
AB  - An unusual case of aggressive Stage IIE(B) primary natural killer cell lymphoma
      of the caecum is described in a 16-year old Chinese girl. The immunophenotype of
      the tumour cells was CD2+, CD3-, CD4-, CD5-, CD7+, CD8-, CD45RO+, CD45RA-, CD56+,
      CD57-. Southern blot analysis showed a normal germline arrangements of the T-cell
      antigen receptor and immuno-globulin heavy chain genes. This lymphoma pursued a
      highly aggressive clinical course, with the rapid development of an extensive
      local recurrence after an apparently complete resection and combination cytotoxic
      therapy. The patient died 7 months after diagnosis, despite receiving salvage
      treatment. Given the aggressiveness and poor prognosis in this biologically
      distinct primary gastrointestinal lymphoma, a more vigorous systemic therapy
      should be considered in addition to surgery.

PMID- 9269557
TI  - Primary non-Hodgkin's lymphoma of the cranial vault.
AB  - We present a case of primary B-cell, large-cell, lymphoma of the skull vault in a
      50-year-old HIV-positive male, who presented with a history of unilateral
      headache and a swelling on the scalp. Primary non-Hodgkin's lymphoma of the skull
      is rare, with only ten such cases in adults previously described. We suggest that
      this is the second reported case in an HIV-positive individual.

PMID- 9269558
TI  - Androgen deprivation and antagonism in the treatment of advanced prostatic
      carcinoma. Vinorelbine: an update and review of activity.

PMID- 9269559
TI  - Accidental administration of vincristine into the brachial artery.

PMID- 9269560
TI  - Real-time NMR investigations of triple-helix folding and collagen folding
      diseases.
AB  - Folding of the collagen triple helix provides an opportunity to look at
      multichain molecular assembly. This triple helix also offers unique advantages
      for the study of folding because the process is very slow compared to globular
      proteins, and the kinetics of folding can be obtained in real time by NMR.
      Studies on triple-helical peptides illustrate the ability to observe kinetic
      folding intermediates directly and the ability to propose detailed mechanisms of
      folding through the use of real-time NMR methods. Defective collagen folding has
      been implicated in various connective tissue diseases and the capacity of NMR to
      look at the folding of specific sites provides a tool for obtaining information
      about altered folding mechanisms. Comparison of folding in peptides that model
      normal and diseased collagens could shed light on the molecular perturbation and
      the etiology of disease.

PMID- 9269562
TI  - Local interactions in a Schellman motif dictate interhelical arrangement in a
      protein fragment.
AB  - BACKGROUND: As an approach to understanding the role of local sequence in
      determining protein tertiary structure, we have examined the conformation of a 23
      residue peptide fragment corresponding to the structurally conserved helix
      Schellman motif-helix (H-Sm-H) domain (residue 10-32) of cellular retinoic acid
      binding protein, along with variants designed to probe the contributions of the
      helix-terminating Gly23 and the hydrophobic interactions between Leu 19 and Val24
      in stabilizing the Schellman motif and hence helix termination. RESULTS: In
      aqueous solution, NMR data for the H-Sm-H peptide show that it samples a largely
      helical conformation with a break in the helix at the point of the turn in the
      protein. The data also establish the presence of local hydrophobic interactions
      and intramolecular hydrogen bonds characteristic of a Schellman motif. Absence of
      helix termination in trifluoroethanol, a solvent known to disrupt hydrophobic
      interactions, along with an analysis of H alpha chemical shifts and NOEs in the
      variant peptides, suggest a major role for glycine in terminating the helix, with
      local hydrophobic interactions further stabilizing the Schellman motif.
      CONCLUSIONS: The presence of a Schellman motif in this isolated fragment in water
      is governed by local interactions and specifies the interspatial arrangement of
      the helices. This observation underlines the structure predictive value of
      folding motifs. As proposed for a Schellman motif, helix termination in this
      fragment is dictated by the local distribution of polar/apolar residues, which is
      reminiscent of the binary code for protein folding.

PMID- 9269561
TI  - Design of two-helix motifs in peptides: crystal structure of a system of linked
      helices of opposite chirality and a model helix-linker peptide.
AB  - BACKGROUND: An attempt is being made to produce two-helix bundles that are
      soluble in apolar media, without the use of a rigid template. The approach relies
      on the use of stereochemically constrained amino acids for helix construction,
      while a flexible linker is obtained by the use of an epsilon-aminocaproic acid
      residue (Acp). The Acp linker has appropriate NH and COOH termini to connect to
      the N and C termini of the helices, a flexible (CH2)5 moiety and sufficient
      length to make the desired assembly. RESULTS: The conformations in crystals
      (determined by X-ray diffraction analyses) are described for a partial assembly
      consisting of a 7-residue helix with Acp (helix-Acp) and for two assemblies of 7
      residue helices with Acp (helix-Acp-helix) in which the chiralities of the
      helices are L,L (already published) and L,D (this publication). The Acp linker is
      extended away from the helix in the L,L analog in a zig-zag manner, but assumes a
      helical conformation in the L,D analog. The two helices in the L,L and L,D
      analogs are displaced laterally by the linker, but in neither case has the linker
      folded the molecule into the desired U-conformation. Cell parameters for Boc-L
      Val-L-Ala-L-Leu-Aib-L-Val-L-Ala-L-Leu-Acp-D-Val-D -Ala-D-Leu-Aib-D-Val-D-Ala-D
      Leu-OMe are space group P4(1) with a = b = 10.094(6) A and c = 93.383(12) A.
      CONCLUSIONS: Strong hydrogen bonds (NH...O=C) between the displaced helices of
      one molecule and the displaced helices of a neighboring molecule, which form near
      the linker of each helix-linker-helix assembly, appear to dominate in both the
      L,L and L,D crystal. The (CH2)5 segment of the linker readily adopts different
      conformations that result in the L and D helices packing in a similar spatial
      motif. Greater conformational control at the linking segment or introduction of
      specific interhelix interactions may be necessary in order to achieve U-type
      folding between neighboring helices in a single molecule.

PMID- 9269563
TI  - Discrete representations of the protein C alpha chain.
AB  - BACKGROUND: When a large number of protein conformations are generated and
      screened, as in protein structure prediction studies, it is often advantageous to
      change the conformation in units of four consecutive residues at a time. The
      internal geometry of a chain of four consecutive C alpha atoms is completely
      described by means of the three angles theta 1, tau, and theta 2, where tau is
      the virtual torsion angle defined by the four atoms and theta 1 and theta 2 are
      the virtual bond angles flanking the torsion angle on either side. In this paper,
      we examine the quality of the protein structures that can be obtained when they
      are represented by means of a set of discrete values for these angles (discrete
      states). RESULTS: Different models were produced by selecting various different
      discrete states. The performance of these models was tested by rebuilding the C
      alpha chains of 139 high-resolution nonhomologous protein structures using the
      build-up procedure of Park and Levitt. We find that the discrete state models
      introduce distortions at three levels, which can be measured by means of the
      'context-free', 'in-context', and the overall root-mean-square deviation of the C
      alpha coordinates (crms), respectively, and we find that these different levels
      of distortions are interrelated. As found by Park and Levitt, the overall crms
      decreases smoothly for most models with the complexity of the model. However, the
      decrease is significantly faster with our models than observed by Park and Levitt
      with their models. We also find that it is possible to choose models that perform
      considerably worse than expected from this smooth dependence on complexity.
      CONCLUSIONS: Of our models, the most suitable for use in initial protein folding
      studies appears to be model S8, in which the effective number of states available
      for a given residue quartet is 6.5. This model builds helices, beta-strands, and
      coil/loop structures with approximately equal quality and gives the overall crms
      value of 1.9 A on average with relatively little variation among the different
      proteins tried.

PMID- 9269564
TI  - Cell dynamics of folding in two-dimensional model proteins.
AB  - BACKGROUND: Functionally useful proteins are sequences of amino acids that fold
      rapidly under appropriate conditions into their native states. It is believed
      that rapid folders are sequences for which the folding dynamics entail the
      exploration of restricted conformations-the phase space can be thought of as a
      folding funnel. While there are many experimentally accessible predictions
      pertaining to the existence of such funnels and a coherent picture of the
      kinetics of folding has begun to emerge, there have been relatively few simple
      studies in the controlled setting of well-characterized lattice models. RESULTS:
      We design rapidly folding sequences by assigning the strongest couplings to the
      contacts present in a target native state in a two-dimensional model of
      heteropolymers. Such sequences have large folding transition temperatures and low
      glass transition temperatures. The dependence of median folding times on
      temperature is investigated. The pathways to folding and their dependence on the
      temperature are illustrated via a study of the cell dynamics-a mapping of the
      dynamics into motion within the space of the maximally compact cells.
      CONCLUSIONS: Folding funnels can be defined operationally in a coarse-grained
      sense by mapping the states of the system into maximally compact conformations
      and then by identifying significant connectivities between them.

PMID- 9269565
TI  - Simultaneous and coupled energy optimization of homologous proteins: a new tool
      for structure prediction.
AB  - BACKGROUND: Homology-based modeling and global optimization of energy are two
      complementary approaches to prediction of protein structures. A combination of
      the two approaches is proposed in which a novel component is added to the energy
      and forces similarity between homologous proteins. RESULTS: The combination was
      tested for two families: pancreatic hormones and homeodomains. The simulated
      lowest-energy structure of the pancreatic hormones is a reasonable approximation
      to the native fold. The lowest-energy structure of the homeodomains has 80% of
      the native contacts, but the helices are not packed correctly. The fourth lowest
      energy structure of the homeodomains has the correct helix packing (RMS 5.4 A and
      82% of the correct contacts). Optimizations of a single protein of the family
      yield considerably worse structures. CONCLUSIONS: Use of coupled homologous
      proteins in the search for the native fold is more successful than the folding of
      a single protein in the family.

PMID- 9269566
TI  - Multiple sequence threading: conditional gap placement.
AB  - Preliminary work to improve on the gap placement in a novel multiple sequence
      threading method is presented here. Using the globin family, we construct
      measures for the assessment of gaps in a multiple sequence threading alignment
      based on the structural comparison of two of the proteins in the family. We take
      into account information from multiple sequence alignments on both the structure
      and sequence side of the problem. This work shows the parameterization of the
      problem allowing the foundation to optimize and test a gap placement weight or
      penalty. Four states were considered: deleted structure, inserted sequence, gap
      ends in structure, and broken ends in sequence. Each of these states was analyzed
      for exposure, occupancy and secondary structure. These measures enable us to gain
      insight into the placement of gaps in a multiple sequence threading alignment. We
      analyzed the most extreme violations of these properties and found in these cases
      that most secondary structures are broken by gaps. However, sequence inserts in
      structure were never found in deeply buried positions. Most end separations were
      3-4 A in excess of the minimum 6 A, although some were larger. We show that the
      maximum amount of observed secondary structure found in inserts was about half of
      the predicted structure (typically 5 and 10%, respectively). A similar trend
      occurred with observed and predicted exposure in inserts. Our eventual aim is to
      devise a weight incorporating these measures of gap placement to further refine
      our algorithm for the threading of sequence on structure.

PMID- 9269567
TI  - Protein thermal stability: hydrogen bonds or internal packing?
AB  - Thermally stable proteins are of interest for several reasons. They can be used
      to improve the efficiency of many industrial processes and provide insight into
      the general mechanisms of protein folding and stabilization. Comparison of
      tertiary structural properties of several protein families with members of
      different thermostability should help to delineate the role of individual factors
      in achieving stability at high temperature. In this work, 16 protein families
      with at least one known thermophilic and one known mesophilic tertiary structure
      were examined for the number and type of hydrogen bonds and salt links, polar
      surface composition, internal cavities and packing densities, and secondary
      structural composition. The results show a consistent increase in the number of
      hydrogen bonds and in polar surface area fraction with increased thermostability.

PMID- 9269568
TI  - Tertiary structure prediction using mean-force potentials and internal energy
      functions: successful prediction for coiled-coil geometries.
AB  - We report a preliminary study of the use of mean-force potentials (MFPs) for
      predicting protein tertiary structure. For three leucine zipper sequences, we
      have calculated ensembles of structures spanning all possible backbone
      conformations consistent with the canonical coiled-coil geometry. MFPs were
      measured with the program PROSA. The MFP alone was poor at discriminating the
      native structure from very divergent structures, and the global minimum of the
      MFP sometimes occurred far from the native structure. We found that adding an
      internal energy function (a subset of the CHARMM potential that describes only
      interactions between backbone atoms), the resultant total energy (CHARMM+PROSA)
      performed much better; in each case, there was a clear positive correlation
      between total energy and root-mean-square deviation (RMSD) from the experimental
      structure, and the lowest-energy structures were about 1 A RMSD from the
      experimental structures. Thus, we conclude that the combined potential is a
      powerful method for predicting leucine zippers and is very promising for general
      3D structure prediction.

PMID- 9269569
TI  - Ambiguous distance data in the calculation of NMR structures.
AB  - The use of molecular dynamics for simulated annealing optimization of structures
      calculated from NMR data is reviewed. I focus on ways of directly using and
      automatically assigning ambiguous peaks from nuclear Overhauser enhancement
      experiments during the structure calculation.

PMID- 9269570
TI  - Protein folding and fold recognition for square lattice models.
AB  - Protein folding and inverse protein folding problems are examined for the
      extremely simplified model of short self-avoiding square lattice walks involving
      only two or three residue types. Simple interresidue contact free energy
      functions are given and are used to determine which sequences fold uniquely to
      which conformations. Contrary to general theories of protein folding, this model
      system shows little correlation between free energy and conformational distance
      from the native, nor is there any marked energy gap between the native and the
      best non-native structures. Furthermore, even the given free energy function
      sometimes fails to identify which sequences fold to a particular target
      structure. If current ideas about protein folding and structure/sequence
      compatibility fail in this model system, it is unclear why they should be valid
      for real proteins.

PMID- 9269571
TI  - Local interactions of aromatic residues in short peptides in aqueous solution: a
      combined database and energetic analysis.
AB  - Although short peptides are usually structurally disordered in aqueous solution,
      particular peptide sequences display local structure. We performed database and
      conformational searches, along with molecular dynamics simulations, to study two
      local interactions detected by 1H-NMR in tetrapeptides excised from bovine
      pancreatic trypsin inhibitor: aromatic-(i+2)amide and (i-1)cisproline-aromatic.
      For both types of interaction, at least two major and distinct peptide
      conformations are identified in the folded state. The aromatic-(i+2)amide
      interaction can have parallel and perpendicular arrangements of the N-H bond and
      the aromatic ring. The (i-1)cisproline-aromatic interaction can have close
      packing of the aromatic ring to the (i-2)C alpha H or the (i-1)C gamma H but not
      both simultaneously. Although these local aromatic interactions are weak, they
      may influence folding and binding properties. The combination of search and
      simulation techniques provides a useful route towards obtaining an atomic-detail
      description of peptides exhibiting these interactions.

PMID- 9269573
TI  - Engineering of metal-ion sites as distance constraints in structural and
      functional analysis of 7TM receptors.
AB  - G-protein-coupled receptors with their seven transmembrane (7TM) segments
      constitute the largest superfamily of proteins known. Unfortunately, still only
      relatively low resolution structures derived from electron cryo-microscopy
      analysis of 2D crystals are available for these proteins. We have used
      artificially designed Zn(II) metal-ion binding sites to probe 7TM receptors
      structurally and functionally and to define some basic distance constraints for
      molecular modeling. In this way, the relative helical rotation and vertical
      translocation of transmembrane helices TM-II, TM-III, TM-V, and TM-VI of the
      tachykinin NK-1 receptor have been restricted. Collectively, these zinc sites
      constitute a basic network of distance constraints that limit the degrees of
      freedom of the interhelical contact faces in molecular models of 7TM receptors.
      The construction of artificially designed metal-ion sites is discussed also in
      the context of probes for conformational changes occurring during receptor
      activation.

PMID- 9269572
TI  - The Levinthal paradox: yesterday and today.
AB  - A change in the perception of the protein folding problem has taken place
      recently. The nature of the change is outlined and the reasons for it are
      presented. An essential element is the recognition that a bias toward the native
      state over much of the effective energy surface may govern the folding process.
      This has replaced the random search paradigm of Levinthal and suggests that there
      are many ways of reaching the native state in a reasonable time so that a
      specific pathway does not have to be postulated. The change in perception is due
      primarily to the application of statistical mechanical models and lattice
      simulations to protein folding. Examples of lattice model results on protein
      folding are presented. It is pointed out that the new optimism about the protein
      folding problem must be complemented by more detailed studies to determine the
      structural and energetic factors that introduce the biases which make possible
      the folding of real proteins.

PMID- 9269574
TI  - Hypochlorite-induced peroxidation of egg yolk phosphatidylcholine is mediated by
      hydroperoxides.
AB  - Using a chemiluminescent method, the consumption of HOCl/OCl- was investigated
      during interaction with liposomes prepared from dimyristoylphosphatidylcholine
      (DMPC) or egg yolk phosphatidylcholine (EYPC). The concentration of HOCl/OCl
      decreased with time in the suspension of EYPC that contain unsaturated lipids and
      did not change in DMPC liposome suspensions. HOCl/OCl- was consumed more rapidly
      in peroxidized EYPC. The amount of double bonds was lowered by 40% in peroxidized
      liposomes and decreased by approximately one-third under the action of HOCl/OCl-
      in both native and peroxidized EYPC samples. Second-order rate constants for the
      interaction between HOCl and phospholipid double bonds of 0.50 M-1 s-1 were
      calculated for native EYPC on basis of the consumption of HOCl/OCl- or from the
      decrease in concentration of double bonds. In peroxidized EYPC this reaction
      constant was similar as determined following changes in double bonds. It is
      concluded that the consumption of HOCl/OCl- increased in peroxidized liposomes
      due to additional reactions with lipid peroxidation products. tert-Butyl
      hydroperoxide and cumene hydroperoxide, or organic peroxides or epoxides (cis
      9,10-epoxystearic acid; cholesterol-5 alpha,6 alpha-epoxide; trans-2,3-epoxy
      butane; cis-2,3-epoxy-butane) were incorporated into liposomes and investigated
      in respect to their ability (1) to increase the consumption of HOCl/OCl- in DMPC
      liposomes, (2) to generate a non-enhanced chemiluminescence with HOCl/OCl- and
      (3) to evoke an accumulation of lipid peroxidation products (TBARS) in EYPC
      liposomes in the absence and presence of NaOCl. None of peroxides or epoxides
      tested showed any effect on the consumption of HOCl/OCl- or the generation of
      chemiluminescence. Nor increase of TBARS both in the absence or presence of
      HOCl/OCl-. In contrast, tert-butyl hydroperoxide and cumene hydroperoxide
      increased the consumption of HOCl/OCl- in DMPC liposomes and mediated a higher
      accumulation of TBARS in EYPC liposomes in the presence of HOCl/OCL- over the
      control. These data suggest that lipid peroxidation in EYPC can be initiated by
      the reaction of HOCl/OCL- with organic hydroperoxides.

PMID- 9269575
TI  - Superoxide dismutase does protect the cultured rat cardiac myocytes against
      hypoxia/reoxygenation injury.
AB  - The effect of superoxide dismutase (SOD) on membrane integrity and fluidity of
      the cultured neonatal rat cardiac myocytes in vitro was investigated under the
      condition of hypoxia and hypoxia/reoxygenation. Lactate dehydrogenase (LDH)
      concentration was used as the biochemical indicator for the loss of cell membrane
      integrity. Fluorescence polarization (FP), average microviscosity (eta) and
      anisotropy (Ast), which are inversely proportional to the fluidity of cell
      membrane, were assayed. Cells were respectively exposed to hypoxia or
      hypoxia/reoxygenation for different periods of time in the absence or presence of
      SOD at various concentrations. Hypoxia alone or hypoxia/reoxygenation brought
      injury to the cultured myocytes. This was demonstrated by changes in LDH and
      membrane fluidity. In the former LDH concentration gradually increased in a time
      dependent manner and the values of FP, eta and Ast were significantly increased.
      The changes in membrane integrity and fluidity induced by hypoxia or
      hypoxia/reoxygenation could be prevented by adding SOD to the culture medium. The
      results provide a direct evidence that SOD (740 u.ml-1, the effective dose) was
      effective in protecting cultured myocytes against the injury as well as an
      indirect evidence of free radical generation. Based on the results obtained from
      this study and the establishment of concept of optimally effective dose by
      Bernier and Omar et al, it was suggested that some previous reports, in which no
      evidence was found both in protective effect of SOD and in free radical
      generation by using only one dose in hypoxia/reoxygenation model, should be
      interpreted with caution.

PMID- 9269576
TI  - Oxidatively damaged erythrocytes are recognized by membrane proteins of
      macrophages.
AB  - Human erythrocytes incubated with an iron catalyst ADP-chelated Fe3+ undergo
      oxidative damage of the membrane including lipid peroxidation, protein oxidation,
      and protein aggregation, and become susceptible to recognition by human
      macrophages. In order to clarify the membrane components of macrophages
      responsible for the recognition of the oxidized erythrocytes, binding of the
      oxidized cells to dot and Western blots of solubilized membrane of macrophages
      was investigated. The oxidized erythrocytes but not unoxidized cells bound to the
      dot blots. The binding was effectively inhibited by saccharide chains of band 3,
      a major glycoprotein of human erythrocytes, and lowered when the saccharide
      chains of band 3 were removed from the cell surface by pretreatment of the cells
      with endo-beta-galactosidase which specifically cleaves the polylactosaminyl
      saccharide chains of band 3. The oxidized erythrocytes bound to the membrane
      proteins of macrophages with molecular mass of about 50, 80, and 120 kDa on
      Western blots depending on the saccharide chains of band 3 on their surface. The
      results suggest that the oxidatively damaged erythrocytes are specifically
      recognized by these proteins of macrophage membrane having saccharide binding
      ability.

PMID- 9269577
TI  - A search for the intermediate radical, ONOO, in the reaction between oxygen and
      nitric oxide in solution.
AB  - The most probable initial reaction between .NO and O2 is direct addition to give
      the peroxyl radical ONOO.. In view of the potential importance of this radical in
      biology, we have searched extensively for its formation, using EPR spectroscopy
      and rapid freezing techniques. At best, only extremely low concentrations were
      detected, and in most systems, no signals were detectable. We conclude that this
      radical is unlikely to be of major importance per se in biological systems, in
      contrast with its one electron adduct, the peroxynitrite anion.

PMID- 9269578
TI  - Hepatic damage influences the decay of nitroxide radicals in mice--an in vivo ESR
      study.
AB  - To determine the role of the liver in the elimination of free radicals from the
      body, the clearance rate (K) of nitroxide radicals (Tempol) at the hepatic domain
      was compared with that at the pelvic domain of live mice, using L-band ESR
      spectroscopy. The reduction of Tempol in biopsy specimens (liver tissue and
      femoral muscle) and blood obtained from Tempol-treated mice was also monitored
      using X-band ESR spectroscopy. Results indicated that the reduction of nitroxide
      radicals was delayed in both the liver and peripheral tissues when the liver was
      damaged. The decrease in both blood supply and reductants in the damaged liver
      might be involved in delaying the reduction in the whole body, because the liver
      can reduce the radicals supplied via the blood from the peripheral tissues, and
      the reductants such as reduced, glutathione in the peripheral tissues are
      supplied from the liver.

PMID- 9269579
TI  - Conversion of nitroxide radicals by phenolic and thiol antioxidants.
AB  - Nitrone/nitroso spin traps are often used for detection of unstable hydroxyl
      radical giving stable nitroxide radicals with characteristic electron spin
      resonance (ESR) signals. This technique may be useful only when the nitroxide
      radicals are kept stable in the reaction system. The aim of the present study is
      to clarify whether the nitroxide radicals are kept stable in the presence of the
      hydroxyl radical scavengers. Effect of hydroxyl radical scavengers on the ESR
      signals of nitroxide radicals, 2,2,6,6-tetramethyl-piperidine- N-oxyl (TEMPO) and
      the spin adduct (DMPO-OH) of 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and hydroxyl
      radical, was examined. Although the ESR signals of TEMPO and the DMPO-OH spin
      adduct were unchanged on treatment with ethanol and dimethyl sulfoxide, their
      intensities were effectively decreased on treatment with 6-hydroxy-2,5,7, 8-tetra
      methylchroman-2-carboxylic acid (Trolox), cysteine, glutathione, 2
      mercaptoethanol and metallothionein. Hence, the results of the detection of
      hydroxyl radical in the presence of phenolic and thiol antioxidants by the ESR
      technique using nitrone/nitroso spin traps may be unreliable.

PMID- 9269580
TI  - Hemin-induced membrane sulfhydryl oxidation: possible involvement of thiyl
      radicals.
AB  - Sublytic levels (microM) of hemin destabilized RBC membrane as indicated by ghost
      fragmentation pattern using a laser viscodiffractometer. Furthermore, electron
      microscopic study shows that 5 microM of hemin induced echinocytic transformation
      whereas higher hemin concentration (40 microM) induced spherocytic
      transformation. In addition, hemin oxidized sulfhydryl groups in a dose dependent
      fashion and Electron Spin Resonance study suggests that such oxidation may
      involve a thiyl radical. Moreover, sulfhydryl compounds enhanced hemin-induced
      lipid peroxidation. Desferroxamine could prevent hemin-induced sulfhydryl
      oxidation as well as hemin-induced decrease in membrane stability. In contrast,
      vitamin E could effectively prevent hemin-induced lipid peroxidation but could
      not prevent hemin-mediated membrane destabilization.

PMID- 9269581
TI  - Biological reactions of peroxynitrite: evidence for an alternative pathway of
      salicylate hydroxylation.
AB  - Salicylate hydroxylation has often been used as an assay of hydroxyl radical
      production in vivo. We have examined here if hydroxylation of salicylate might
      also occur by its reaction with peroxynitrite. To test this hypothesis, we
      exposed salicylate to various concentrations of peroxynitrite, in vitro. We
      observed the hydroxylation of salicylate at 37 degrees C by peroxynitrite at pH
      6, 7 and 7.5, where the primary products had similar retention times on HPLC to
      2,3- and 2,5-dihydroxybenzoic acid. The product yields were pH dependent with
      maximal amounts formed at pH 6. Furthermore, the relative concentration of 2,3-
      to 2,5-dihydroxybenzoic acid increased with decreasing pH. Nitration of
      salicylate was also observed and both nitration and hydroxylation reaction
      products were confirmed independently by mass spectrometry. The spin trap N-t
      butyl-alpha-phenylnitrone (PBN), with or without dimethyl sulfoxide (DMSO), was
      incapable of trapping the peroxynitrite decomposition intermediates. Moreover,
      free radical adducts of the type PBN/.CH3 and PBN/.OH were susceptible to
      destruction by peroxynitrite (pH 7, 0.1 M phosphate buffer). These results
      suggest direct peroxynitrite hydroxylation of salicylate and that the presence of
      hydroxyl radicals is not a prerequisite for hydroxylation reactions.

PMID- 9269582
TI  - Kinetics of reduction of hypervalent iron in myoglobin by crocin in aqueous
      solution.
AB  - Crocin in aqueous solution is oxidized by ferrylmyoglobin, MbFe(IV) = O, in a
      second order reaction with k = 183 l.mol-1.s-1, delta H++298 = 55.0 kJ.mol-1, and
      delta S++298 = -17 J.mol-1.K-1 (pH = 6.8, ionic strength 0.16 (NaCl), 25 degrees
      C), as studied by stopped-flow spectroscopy. The reaction has 1:1 stoichiometry
      to yield metmyoglobin, MbFe(III), and has delta G theta = -11 kJ.mol-1, as
      calculated from the literature value E0 = +0.85 V (pH = 7.4) vs. NHE for
      MbFe(IV)=O/MbFe(III) and from the half-peak potential +0.74 V (vs. NHE in aqueous
      0.16 NaCl, pH = 7.4) determined by cyclic voltammetry for the one-electron
      oxidation product of crocin, for which a cation radical structure is proposed and
      which has a half-peak potential of +0.89 V for its formation from the two
      electron oxidation product of crocin. The ferrylmyoglobin protein-radical,
      MbFe(IV)=O, reacts with crocin with 2:1 stoichiometry to yield MbFe(IV)=O, as
      determined by ESR spectroscopy, in a reaction faster than the second order
      protein-radical generating reaction between H2O2 and MbFe(III), for which latter
      reaction k = 137 l.mol-1.s-1, delta H++298 = 51.5 kJ.mol-1, and delta S++298 = 
      31 J.mol-1.K-1 (pH = 6.8, ionic strength = 0.16 (NaCl), 25 degrees C) was
      determined. Based on the difference between the stoichiometry for the reaction
      between crocin and each of the two hypervalent forms of myoglobin, it is
      concluded in agreement with the determined half peak reduction potentials, that
      the crocin cation radical is less reducing compared to crocin, as the cation
      radical can reduce the protein radical but not the iron(IV) centre in hypervalent
      myoglobin.

PMID- 9269583
TI  - Seasonal variation in low density lipoprotein oxidation and antioxidant status.
AB  - Accumulating evidence indicates that oxidative modification of low-density
      lipoproteins is atherogenic and that antioxidants may play a role in protection
      of LDL against oxidation. Several studies have reported a seasonal fluctuation in
      antioxidant levels, but to date nothing is known about seasonal fluctuations in
      parameters of oxidizability. We collected blood from 10 volunteers at four
      different periods over one year (February, May, September and December), and
      measured the amount of plasma lipids, plasma antioxidants, lipid and fatty acid
      composition of the LDL particle, LDL antioxidant content, LDL particle size and
      oxidation parameters (lag time and propagation rate). No seasonal fluctuation for
      lag time and propagation rate of copper ion-induced LDL oxidation was found.
      Small seasonal fluctuations were observed for some determinants of LDL oxidation,
      e.g. plasma and LDL vitamin E and LDL particle size, and for plasma lipids,
      plasma and LDL lutein and LDL beta-carotene. Fatty acid composition of LDL did
      not change during the year. The main determinant of oxidation susceptibility was
      the fatty acid composition of LDL. We conclude that LDL oxidation parameters do
      not change over the year.

PMID- 9269584
TI  - Enhanced protection against peroxidation-induced mortality of aortic endothelial
      cells by ascorbic acid-2-O-phosphate abundantly accumulated in the cell as the
      dephosphorylated form.
AB  - Bovine aortic endothelial BAE-2 cells exposed to the peroxidizing agent, tert
      butylhydroperoxide (t-BuOOH) or 2,4-nonadienal (NDE), suffered from disruption of
      cell membrane integrity and from reduction of mitochondrial dehydrogenase
      activity as assessed by fluorometry using ethidium homodimer and photometry using
      WST-1, respectively. The cells were protected from t-BuOOH-induced injury more
      markedly by L-ascorbic acid-2-O-phosphate (Asc2P) stably masked at the 2,3
      enediol moiety, which is responsible for the antioxidant ability of L-ascorbic
      acid (Asc), than by Asc itself. In contrast, NDE-induced membrane disruption but
      not mitochondrial dysfunction was prevented by Asc2P, whereas Asc exhibited no
      prevention against both types of injury. The amount of intracellular Asc was 7.2-
      to 9.0-fold larger in Asc2P-administered BAE-2 cells, where the intact from Asc2P
      was not detected, than in Asc-administered cells as assessed by HPLC of cell
      extract with detection by coulometric ECD and UV. During transmembrane influx
      into the cell, Asc2P was concentrated as highly as 70- to 90-fold relative to the
      extracellular Asc2P concentration, whereas Asc was 8- to 13-fold concentrated as
      estimated based on an intracellular water content of 0.59 pL/cell determined by
      [14C]PEG/gas chromatography. Thus, Asc2P but not Asc is highly concentrated in
      the aqueous phase of the cell after prompt dephosphorylation, and may thereby
      render the cell more resistant to t-BuOOH-peroxidation assumedly via scavenging
      of intracellular reactive oxygen species than to peroxidation with the less
      hydrophilic agent NDE.

PMID- 9269585
TI  - alpha-Tocopherol binding activity of red blood cells in smokers.
AB  - Despite high plasma levels of vitamin E, red blood cell membranes contain
      relatively low levels of vitamin E. This suggests the existence of a selective
      vitamin E uptake/regeneration system in human red blood cell membranes. alpha
      Tocopherol binding sites on human red blood cells are thought to be involved in
      the uptake of alpha-tocopherol from the plasma. To understand the role of the
      uptake system we have compared the alpha-tocopherol content and binding activity
      of red blood cells from smokers and non-smokers. The specific binding of [3H]
      alpha-tocopherol to pure red blood cell preparations from smokers (n = 7, 28.4 +/
      2.8 years) was 30.6 +/- 3.2 fmoles per 3 x 10(8) red blood cells and for non
      smokers (n = 17, 27.9 +/- 1.3 years) was 41.7 +/- 3.7 fmoles per 3 x 10(8) red
      blood cells. Thus alpha-tocopherol uptake activity was significantly lower in
      smokers (P = 0.05). Red blood cells from smokers contained less (1.8 +/- 0.4
      micrograms/gHb) alpha-tocopherol than non-smokers (2.8 +/- 0.3 micrograms/gHb),
      (P < 0.05), despite plasma levels of alpha-tocopherol being similar: 12.9 +/- 0.8
      microM in non-smokers vs. 12.7 +/- 0.5 microM in smokers. However, adjusting
      plasma alpha-tocopherol for total plasma cholesterol plus triacylglycerols showed
      alpha-tocopherol levels were higher (P < 0.01) in non-smokers (2.84 +/- 0.10
      mumol alpha-tocopherol/ mmol [cholesterol+triacylglycerol]) than in smokers (2.36
      +/- 0.11 mumol alpha-tocopherol/mmol [cholesterol+triacylglycerol]). The reduced
      alpha-tocopherol levels in red blood cells from smokers may be due to impairment
      of alpha-tocopherol uptake activity. The reduced levels of alpha-tocopherol in
      smokers red blood cells was not associated with any changes in cell membrane
      fluidity. At present it is not known whether supplementation of smokers with
      vitamin E would normalise the alpha-tocopherol uptake activity of red blood
      cells.

PMID- 9269594
TI  - Exanthemata and the eye.

PMID- 9269586
TI  - Effects of co-supplementation of iron with ascorbic acid on antioxidant--pro
      oxidant balance in the guinea pig.
AB  - The relationship between intake of iron with ascorbic acid and their uptake into
      the plasma and liver of guinea pigs was studied. The influence on the
      antioxidant/pro-oxidant balance of liver microsomes was also determined. Animals
      were fed a standard pelleted diet low in iron and ascorbic acid for 35 days. The
      pellet diet was supplemented by oral dosing with a solution containing either
      maintenance dietary levels of ascorbic acid and iron, or one of three regimens
      that increased the dosage of these substances ten fold. There were no significant
      differences in animal growth rate or food intake between these regimens. Liver
      and plasma total ascorbate levels were significantly increased (p < 0.05) in
      animals receiving either ascorbic acid alone (liver 126 +/- 36 micrograms/g
      tissue wet wt. and plasma 51.7 +/- 17.0 microM; n = 9) or ascorbic acid and iron
      (105 +/- 18 micrograms/g and 40.3 +/- 15.3.0 microM; n = 8) compared to controls
      (84 +/- 36 micrograms/g and 15.3 +/- 8.5 microM; n = 11). Total iron levels in
      the liver (76.7 +/- 7.3 micrograms/g; control; n = 6) and plasma (2.4 +/- 0.03
      mg/l; control) were not significantly raised in animals under these conditions of
      iron or ascorbate intake. Liver microsomes isolated from animals receiving iron
      had a greater susceptibility to oxidative stress in terms of malondialdehyde
      production during auto-oxidation compared to those from control animals under the
      same conditions. This effect was eliminated on combining ascorbic acid with the
      iron supplementation, suggesting that oral administration of vitamin C has a
      protective rather than a pro-oxidant effect under these circumstances.

PMID- 9269595
TI  - The ocular manifestations of Lyme disease.
AB  - LD (with its ocular manifestations) is a worldwide disorder that is increasing in
      frequency. It is a treatable multisystemic disease that presents in three stages
      of severity. It can present with unusual forms of conjunctivitis, keratitis,
      cranial nerve palsies, optic nerve disease, uveitis, vitreitis, and other forms
      of posterior segment inflammatory disease. A patient with any of these ocular
      manifestations should be questioned for exposure to an area endemic for LD, tick
      bites, skin rash, or arthritis. Such patients should undergo serological testing.
      If the clinical presentation is suggestive of LD, a course of oral antibiotics
      should be used (unless the patient gives a history of adequate therapy). Topical
      corticosteroids can be used for anterior segment inflammation. An antibiotic
      therapeutic trial can be used for posterior segment or neuroophthalmic disease.
      Systemic corticosteroids without concomitant antibiotics should not be used in
      the treatment of ocular LD. If ocular LD is discovered and treated early,
      response to therapy usually is satisfactory.

PMID- 9269596
TI  - Rosacea.

PMID- 9269597
TI  - Psoriasis, ichthyosis, and porphyria.

PMID- 9269598
TI  - Ocular cicatricial pemphigoid and ocular manifestations of pemphigus vulgaris.

PMID- 9269599
TI  - Stevens-Johnson syndrome, epidermolysis bullosa, staphylococcal scalded skin
      syndrome, and dermatitis herpetiformis.

PMID- 9269600
TI  - Systemic lupus erythematosus, discoid lupus erythematosus, and progressive
      systemic sclerosis.

PMID- 9269601
TI  - Atopic keratoconjunctivitis.

PMID- 9269602
TI  - The ocular manifestations of graft-versus-host disease.

PMID- 9269604
TI  - Overcoming Streptococcus agalactiae in vitro resistance to imidazoles.
AB  - The increased diffusion of Streptococcus agalactiae in the urinary tract and
      vagina has affected the strain's resistance to antimicrobial agents, so we
      decided to study the possibility of overcoming its resistance to imidazoles. Our
      data suggest that overcoming S. agalactiae resistance to imidazoles in contact
      and growth culture tests depends partly on the electrical conductivity of the
      culture medium. Although imidazole contact activity and culture activity have
      different targets in cell structures, we have demonstrated that imidazole
      resistance in S. agalactiae cells in both types of tests can be affected by the
      same conditions regulating membrane permeability.

PMID- 9269603
TI  - Rapid drug susceptibility of Mycobacterium avium complex using a fluorescence
      quenching method.
AB  - Mycobacteria Growth Indicator Tube (MGIT) is a recently introduced rapid growth
      detection method which uses an oxygen quenched fluorescent indicator. The present
      study evaluated the ability of this new method to determine the drug
      susceptibility of Mycobacterium avium complex (MAC). Thirty strains recovered
      from patients with AIDS were tested for susceptibility to clarithromycin,
      rifabutin, ciprofloxacin, azithromycin and amikacin using MGIT. Results were
      compared to susceptibilities determined by the agar dilution method. The results
      obtained showed a 100% correlation between MGIT and the agar dilution method for
      rifabutin and clarithromycin. There was a 100% correlation between the two
      methods for azithromycin against 27 strains. MGIT was well correlated with the
      agar dilution method for detecting resistance to clarithromycin, rifabutin and
      azithromycin in 4 days, but the correlation was poor when susceptibilities to
      ciprofloxacin and amikacin were determined. This rapid method is non-radiometric,
      noninvasive and does not require any special instruments.

PMID- 9269605
TI  - Penetration of topically applied ciprofloxacin, norfloxacin and ofloxacin into
      the aqueous humor of the uninflamed human eye.
AB  - This study was undertaken to compare aqueous humor penetration of topical 0.3%
      ciprofloxacin, 0.3% norfloxacin and 0.3% ofloxacin in 63 patients undergoing
      cataract surgery. The patients were divided into two groups. Group 1 (long-term
      treatment) involved 30 patients undergoing cataract extraction who received
      either 0.3% ciprofloxacin, 0.3% norfloxacin or 0.3% ofloxacin topical drops. Each
      patient was preoperatively given a single drop per hour six times. At the time of
      surgery, 0.1 ml aqueous fluid was aspirated from the anterior chamber and
      immediately stored at -70 degrees C. Topically applied ciprofloxacin, ofloxacin
      and norfloxacin achieved mean aqueous humor levels of 2.80 +/- 1.07, 2.95 +/-
      1.19 and 1.50 +/- 0.48 micrograms/ml respectively. There was no statistically
      significant difference in intraocular mean aqueous levels of ciprofloxacin versus
      ofloxacin. Topical ciprofloxacin and ofloxacin achieved mean aqueous humor levels
      significantly higher than norfloxacin (p < 0.001 and p < 0.0008 respectively).
      Group 2 (short-term treatment) involved 33 patients undergoing cataract
      extraction who received 0.3% ciprofloxacin, 0.3% ofloxacin and 0.3% norfloxacin
      topical drops. These patients were given one drop at 90 minutes and one drop 30
      minutes preoperatively. At the time of surgery, 0.1 ml aqueous fluid was
      aspirated from the anterior chamber and immediately stored at -70 degrees C.
      Topically applied ciprofloxacin, ofloxacin and norfloxacin achieved mean aqueous
      humor levels of 1.11 +/- 0.50, 1.50 +/- 0.62 and 1.20 +/- 0.43 micrograms/ml
      respectively. There was no statistically significant difference in intraocular
      mean aqueous humor levels of ofloxacin versus norfloxacin and ciprofloxacin
      versus norfloxacin. Topical ofloxacin achieved a significantly higher mean
      aqueous humor level than ciprofloxacin (p < 0.03). All levels were above the
      minimum inhibitory concentrations of ciprofloxacin, ofloxacin and norfloxacin for
      most of the sensitive organisms.

PMID- 9269606
TI  - Comparative trial of azithromycin and ciprofloxacin in the treatment of
      gonorrhea.
AB  - This single-blind (investigator) comparative study was designed to determine the
      efficacy and tolerability of 1 g of azithromycin vs 500 mg of ciprofloxacin both
      given as a single oral dose in patients with gonorrhea, who were constantly on
      the move. One hundred eight patients (59 men and 49 women) with clinically
      suspected gonococcal infection, confirmed by Gram-stain and culture, were
      enrolled. Data of 50 patients treated with azithromycin and 51 with ciprofloxacin
      were evaluable for efficacy and tolerability at the end of the study. After 2
      weeks clinical and microbiological cure rates were 96.0% (48 out of 50) for the
      patients treated with azithromycin and 92.15% (47 out of 51) for the patients
      treated with ciprofloxacin (p > 0.05). Adverse reactions were reported in 5
      patients treated with azithromycin and 6 with ciprofloxacin. In conclusion, 1 g
      azithromycin is at least as clinically and microbiologically effective and well
      tolerated as 500 mg of ciprofloxacin in the treatment of gonococcal infections.
      The drug is particularly useful for sailors and people constantly on the move.

PMID- 9269607
TI  - Piperacillin-tazobactam as empiric monotherapy in febrile neutropenic patients
      with haematological malignancies.
AB  - The efficacy of piperacillin-tazobactam as first line empiric therapy was
      assessed in 54 febrile neutropenic episodes in 42 patients (27 male, 15 female)
      with haematological malignancy. Nineteen (35%) episodes were bacteraemias (15
      Gram-positive, 4 Gram-negative), 5 (9%) were clinically documented (Hickman line
      sites) and 30 (56%) were pyrexias of unknown origin. Study therapy was initiated
      after a median of 4 days of neutropenia (range 1-30). Eighteen (33%) episodes
      responded to piperacillin-tazobactam without a need for treatment modification.
      Four (7%) episodes initially responded to piperacillin-tazobactam but required
      treatment modification for fungal superinfection. Of the 19 bacteraemias, 6 (32%)
      were eradicated or presumed eradicated by piperacillin-tazobactam. Of the 32
      (60%) episodes which failed to respond to piperacillin-tazobactam, 11 (34%)
      responded to anti-fungal therapy; 14 (44%) responded to a glycopeptide and 5
      (16%) responded to a second-line broad spectrum antibacterial agent. Two (6%)
      patients died, both in the presence of progressive malignancy. There was no
      significant toxicity associated with piperacillin-tazobactam. We conclude that
      piperacillin-tazobactam is effective as empiric monotherapy in neutropenic fever
      and may reduce the requirement for glycopeptides.

PMID- 9269608
TI  - Clinical efficacy of a vaccine-immunostimulant combination in the prevention of
      influenza in patients with chronic obstructive pulmonary disease and chronic
      asthma.
AB  - Influenza is a leading cause of morbidity and mortality in patients with chronic
      respiratory diseases. This study compares two influenza prevention schemes in
      patients with chronic obstructive pulmonary disease and chronic asthma. We
      enrolled 66 patients, distributed as follows: Group A: 32 subjects treated with
      influenza vaccine; Group B: 34 patients treated with influenza vaccine and
      bacterial immunostimulant. The rate of influenza episodes was recorded.
      Hemoagglutination inhibiting antibody titers for vaccine strains H1N1, H3N2, and
      B were determined at time 0 (prior to vaccination), and on days 30 and 90
      following vaccination. We observed a lower rate of influenza episodes in Group B
      patients (8.82%) compared to Group A (31.25%) (p < 0.05). At day 90 Group B
      patients presented higher geometric mean antibody titers for strains H1N1 (p =
      0.07) and H3N2 (p = 0.08). Bacterial immunostimulants appear as possible
      adjuvants in the prevention of influenza episodes, and may prolong antibody
      response to influenza vaccine strains.

PMID- 9269609
TI  - A five-day course of dirithromycin in the treatment of acute exacerbation of
      severe chronic obstructive pulmonary disease.
AB  - Since dirithromycin persists at high concentrations in the lung for at least 3
      days following the last dose of a 5-day course, we evaluated the clinical
      efficacy and tolerance of a 5-day course of dirithromycin in 20 patients with
      acute exacerbation of severe chronic obstructive pulmonary disease, treated with
      a total dose of 2.5 g dirithromycin (500 mg once-daily for 5 days) in an open,
      non-comparative study. Patients were assessed before therapy and after 5 (last
      administration), 10 (post-therapy) and 20 (late post-therapy) days. Pathogen
      elimination or presumed elimination was seen in 18/20 patients at the post
      therapy visit and at the late post-therapy visit, but two Haemophilus influenzae
      out 5 were isolated in sputum after 10 days and only one after 20 days
      (Pseudomonas aeruginosa was the other pathogen). Dirithromycin was well-tolerated
      and only 2 patients reported mild gastrointestinal pain. This study shows that a
      5-day dirithromycin therapy provides a convenient and efficient dosage regimen in
      acute exacerbation of chronic bronchitis. Notwithstanding its poor in vitro
      activity against H. influenzae, dirithromycin was fairly active against this
      microorganism in vivo.

PMID- 9269610
TI  - Etiology and therapy of community-acquired pneumonia.
AB  - The Authors report the data of a retrospective study performed on 520 patients
      admitted to the Institute of Respiratory Diseases, University of Sassari, Italy,
      for community acquired pneumonia (CAP) from 1980 to 1995. The aim of this study
      was to investigate: the frequency of risk factors and their impact on severity of
      pneumonia; the frequency of pathogens and their correlation with the severity of
      the illness; antibiotic treatments. One or more risk factors were found in 86% of
      patients, while 14% had none. In 286 patients (55%) no etiological diagnosis was
      possible, while in 234 patients (45%) the pathogen was identified. Of the latter,
      73% suffered from pneumonia caused by Gram-negative bacilli, 24% by Gram-positive
      organisms, 0.8% by Mycoplasma pneumoniae and 1.7% by respiratory viruses and
      endemic fungi. The mortality rate found was 2.69%. In this study, pneumonia
      caused by Gram-negative bacilli showed a plurilobar and often bilateral
      involvement, frequent resistance to the most common antibiotics, which required
      longer hospitalization (> 30 days). The high prevalence of pneumonia caused by
      Gram-negative bacilli can be explained by the presence in most of the patients,
      of serious and numerous risk factors.

PMID- 9269611
TI  - Neoadjuvant chemotherapy for osseous malignant fibrous histiocytoma of the
      extremity: results in 18 cases and comparison with 112 contemporary osteosarcoma
      patients treated with the same chemotherapy regimen.
AB  - Eighteen patients with high grade malignant fibrous histiocytoma (MFH) of bone
      and 112 patients with high grade osteosarcoma (OS) of the extremity were treated
      with neoadjuvant chemotherapy comprised of methotrexate, cisplatinum, doxorubicin
      and ifosfamide. For the 18 patients with MFH, surgery involved amputation in 2
      cases and limb salvage in 16 (89%); the 112 osteosarcoma patients had amputation
      in 8 cases and limb salvage procedure in 104 cases (93%). The rate of good
      histologic response to preoperative chemotherapy (90% or more tumor necrosis) was
      significantly higher in patients with osteosarcoma than in patients with MFH (74%
      vs 28%; p < 0.003). However, at a median follow-up of 38 months (range 25-61),
      the 3-year event-free survival (EFS) did not differ in the two groups (MFH 77.8%,
      OS 70.5%; p = ns). In patients with MFH, no local recurrences were registered,
      whereas in the osteosarcoma group there were 6 local relapses (5.%). The
      effectiveness of neoadjuvant chemotherapy in the treatment of osteosarcoma has
      been assessed during the last 15 years. The results of the present study seem to
      indicate that, in spite of a usually poor histologic response to preoperative
      treatment, neoadjuvant chemotherapy is very effective also in MFH of bone.

PMID- 9269612
TI  - Long-term toxicity in adjuvant treatment with tamoxifen.
AB  - Long-term treatment with tamoxifen has produced few side effects, which are
      generally mild. Of the serious ones, all of them except eye toxicity seem to be
      related to the molecule's intrinsic mildly estrogen-like action, such as, for
      example, endometrial carcinoma. This property is also responsible for some
      favorable clinical effects including a lower risk of osteoporosis and
      cardiovascular disease. Whether tamoxifen causes neoplastic growth in patients
      who develop resistance to this drug is still controversial. Further prospective
      clinical studies are therefore needed to investigate such problems and also to
      evaluate less frequent side effects. Moreover, decisions on the overall duration
      of hormone therapy should be based on possible side effects as well as on
      therapeutic response.

PMID- 9269613
TI  - Vinorelbine chemotherapy in non small cell lung cancer: experience in elderly
      patients.
AB  - This study involved 25 elderly (> 65 years old) patients (pts) with unresectable
      non small cell lung cancer (NSCLC) who were not eligible for polychemotherapy.
      The diagnosis of NSCLC was histologically or cytologically documented, and all of
      them had measurable or evaluable disease. The median age of the patients was 71
      (range 65-77); 9 had been pretreated. The pts received 25 mg/m2 of vinorelbine
      weekly or bi-weekly depending on the results of blood tests. The treatment
      continued until disease progression or tolerance. No complete response was
      achieved: 3 pts (12%) had a partial response (RP) (8-12-14 months), 13 (52%)
      stable disease (SD) with an improvement in symptoms, such as cough and/or pain,
      and 9 pts (36%) progressed. Compliance with the therapy was acceptable. The main
      toxicity was hematological: neutropenia was observed in 16 pts, with only 1 case
      of grade 4 neutropenia without sepsis; grade 1-2 anemia occurred in 8 patients.
      The other toxicities included grade 1-2 neurotoxicity in 8 pts, chemical
      phlebitis in 2 pts and grade 3 cardiotoxicity reversible with medical treatment
      in 1 patient. The median survival time was 10 months (lower quartile 5 months,
      upper quartile 23 months) (Kaplan and Meyer method). Vinorelbine can be
      considered a rational choice in elderly pts with advanced NSCLC who are not
      suitable for aggressive polychemotherapy, with the aim of improving their quality
      of life in terms of symptoms and outpatient treatment.

PMID- 9269614
TI  - Assessment of errors when expiratory condensate PCO2 is used as a proxy for mixed
      expired PCO2 during mechanical ventilation.
AB  - OBJECTIVES: We designed a series of experiments to determine whether expiratory
      water condensate (PconCO2) can be used as a proxy for mixed expired gas
      collection. METHODS: In 18 adult mechanically ventilated patients with ARDS (40
      samples), simultaneous collections of arterial blood, expiratory water trap
      condensate, mixed expired gas, and minute ventilation were used to calculate VCO2
      and VD/VT. To assess the effect of temperature, a constant gas flow (PCO2 10-30
      mm Hg) was bubbled through water at temperatures of 19.5-37 degrees C. Gas and
      water samples were collected, immediately analyzed for PCO2, and a temperature
      correction factor was calculated. A lung model was constructed using a 5 L
      anesthesia bag connected to a mechanical ventilator with a heated humidifier.
      Temperature at the Y-piece was set to approximately 37 degrees C and CO2 was
      injected into the bag to establish an end-tidal PCO2 of 20-70 mm Hg. After
      equilibration, condensate was collected, PCO2 was measured, and the temperature
      corrected PCO2 was compared to PECO2. The capnogram at points along the
      expiratory limb circuit was used to evaluate gas mixing. RESULTS: There was an
      over-estimation of PECO2 by PconCO2 (p < 0.001) for the patient data, resulting
      in an underestimation of VD/VT (p < 0.001) and an overestimation of VCO2 (p <
      0.001). The temperature correction factor for PCO2 in water was -0.010 (about
      half of the factor used for whole blood). The bias between temperature-corrected
      PconCO2 and PECO2 was 0.3 +/- 3.2 mm Hg in the lung model. Mixing in the
      expiratory limb was poor, as evaluated by the capnogram. CONCLUSIONS: Even with
      temperature correction, we failed to precisely predict PECO2 from PconCO2. For
      measurement of VD/VT and VCO2, we do not recommend methods that use PconCO2.

PMID- 9269615
TI  - Arterial-pulse oximetry loops: a new method of monitoring vascular tone.
AB  - OBJECTIVE: We report the off-line calculation of the vascular compliance of the
      finger and suggest the continuous on-line use of this methodology as an aid to
      monitoring the peripheral vascular resistance. This method consists of the
      simultaneous analysis of the waveform signals from the pulse oximeter monitors
      and the arterial pressure as indicators of "volume" and pressure respectively to
      continuously calculate the vascular "compliance" (volume change per unit pressure
      change). This should be seen as a "relative compliance" as the pulse
      plethysmograph signal is not calibrated. This new methodology allows for
      continuous monitoring of peripheral vascular compliance as a beat-to-beat
      indicator of peripheral vascular resistance. The vaso-constrictors, phenylephrine
      and ephedrine, were shown to decrease the compliance as predicted. METHODS: The
      arterial pressure and pulse oximeter waveforms were obtained during routine
      anesthetic care. The waveforms were collected with a computer data-acquisition
      system and then analyzed "off-line" as an indirect indicator of total vascular
      tone. Demographic and clinical information including drug administration were
      recorded. RESULTS: A case report is presented using this new form of analysis.
      Vascular compliance changes induced by phenylephrine and ephedrine were studied.
      A dose response curve of peripheral vascular compliance to phenylephrine was
      generated from these data. CONCLUSIONS: By plotting the pulse oximeter waveforms
      versus the arterial waveforms, multiple volume versus pressure (relative
      compliance) loops were obtained. Analysis of these loops may assist in the
      monitoring of vascular compliance.

PMID- 9269616
TI  - Audio signal feedback light source-guided endotracheal intubation.
AB  - OBJECTIVE: Light source-guided endotracheal intubation, whether by lighted stylet
      or fiber-optic laryngoscopy may potentially be improved by electrical conversion
      of the detected optical signal to an audio signal. The audio signal thus serves
      as a feedback guiding signal. METHODS: The optical-to-audio signal conversion is
      accomplished using a light source, an optical detector and a voltage-to-frequency
      conversion system. The intensity of the detected optical signal determines the
      frequency of the audio-signal. Therefore the frequency of the audio signal varies
      as the light source approaches the optical detector. The light source may be
      placed in the orotracheal airway and the detector may be placed on cricothyroid
      membrane or these components may be placed in the opposite orientation. RESULTS:
      The theory of operation and the construction of a prototype are described.
      CONCLUSION: This optical-audio signal feedback system may be used to direct the
      lighted stylet from the oral cavity into the laryngeal-tracheal pathway. This may
      potentially be a more sensitive technique than the currently used visual
      intensity detection.

PMID- 9269617
TI  - Near continuous cardiac output by thermodilution.
AB  - A new thermodilution method for frequent (near continuous) estimation of cardiac
      output, without manual injection of fluid into the blood, was tested. The method
      utilizes a pulmonary artery catheter equipped with a fluid filled heat exchanger.
      The technique is based on cyclic cooling of the blood in the right atrium and
      measurement of the temperature changes in the pulmonary artery. Using this
      technique, a new estimate of cardiac output can be obtained every 32 s. Cardiac
      output estimates, obtained for a running mean of three measurements with this
      method, were compared to the mean of three conventional thermodilution
      measurements. The measurements were obtained during short periods of stable
      respiration and circulation. In six pigs, we made 46 paired measurements of
      conventional thermodilution (TD) and near continuous (TDc) thermodilution. The
      cardiac output (COTD) ranged from 2.4-13.7 l/min (mean 5.4 l/min). The best
      linear fit through the paired data points was COTDc = -0.57 + 1.01 COTD. The mean
      difference between the methods was -0.50 l/min (S.D. = 0.39). The mean
      coefficient of variation of repeated measurements with the near continuous
      thermodilution was 3.6%. Considering changes of more than 0.25 l/min to be
      significant, all changes in cardiac output measured by conventional
      thermodilution were followed by the running mean of three near continuous
      thermodilution estimates. This study demonstrates the feasibility of the new
      method to monitor cardiac output, and to detect all changes greater than 0.25
      l/min.

PMID- 9269618
TI  - Nitric oxide (NO) measurement accuracy.
AB  - BACKGROUND: Evaluation of the clinical utility of NO requires accurate assessment
      of inspired [NO]. Currently, chemiluminescence analyzers are the clinical
      standard for analysis; however, their performance in the clinical setting has not
      been systemically evaluated. METHODS: We evaluated the performance of four
      chemiluminescence analyzers (270B NOA, Sievers Instruments, Inc.; CLA 510S,
      Horiba Co., Ltd.; CLD 700 AL, Eco Physics Corp.; Model 42, Thermo Environmental
      Instruments Inc.) in simulated clinical settings. Transport delay and dynamic 95%
      response time were measured by the balloon in a glass chamber puncture technique.
      Fluctuating [NO] in a continuous flow of gas and [NO] during mechanical
      ventilation, where NO was premixed prior to entering the ventilator, were
      evaluated. RESULTS: Transport delay ranged from 1.02 +/- 0.02 to 24.36 +/- 2.47 s
      (p < 0.05) and the 95% response time ranged from 0.22 +/- 0.04 to 70.03 +/- 0.03
      s (p < 0.05). Accurate analysis of [NO] in a continuous flow system was only
      possible with the most rapid response analyzer (270B NOA). All other analyzers
      under reported the maximum [NO] (p < 0.05) and over reported the minimum [NO] (p
      < 0.05). All analyzers accurately determined [NO] in the inspiratory limb of the
      ventilator circuit, but none accurately determined [NO] at the airway opening.
      CONCLUSIONS: Measurements of inhaled [NO] can vary greatly, dependent upon the
      performance characteristics of the analyzer and the location of NO analysis. All
      studies evaluating the clinical use of NO should fully describe the technical gas
      delivery methodology and the response time and transport delay of the
      chemiluminescence analyzer used.

PMID- 9269619
TI  - An integrated graphic data display improves detection and identification of
      critical events during anesthesia.
AB  - OBJECTIVE: To show that an integrated graphic data display can shorten the time
      taken to detect and correctly identify critical events during anesthesia.
      METHODS: We developed a graphic display which presents 30 anesthesia-related
      physiologic variables as shapes and colors, rather than traditional digits and
      waveforms. To evaluate the new display, we produced four critical events on a
      computer-based anesthesia simulator and asked two groups of five
      anesthesiologists to identify the events as quickly as possible. One group
      observed the new display while the other group viewed a traditional
      cardiovascular monitor with digital and waveform displays. RESULTS: The group
      which observed the integrated graphic display saw changes caused by inadequate
      paralysis 2.4 min sooner, and changes caused by a cuff leak 3.1 min sooner than
      those observing the traditional display. The integrated display group correctly
      identified the reason for the change 2.8 min sooner for inadequate paralysis, 3.1
      min sooner for cuff leak and 3.1 min sooner for bleeding. These differences were
      all statistically significant. CONCLUSIONS: The results show that some simulated
      critical events are detected and correctly identified sooner, when an
      anesthesiologist views an integrated graphic display, rather than a traditional
      digital/waveform monitor.

PMID- 9269621
TI  - Cardiogenic oscillations may be masked by the breathing system configuration.

PMID- 9269620
TI  - Clinical evaluation of an automatic blood pressure controller during cardiac
      surgery.
AB  - OBJECTIVE: During surgery, computers can be of great use to support the
      anesthesiologist in providing task automation. In this paper we describe a closed
      loop blood pressure controller and show the results of its clinical evaluation.
      METHODS: The controller is based on a simple and robust Proportional-Integral
      controller and a supervising, rule based, expert system. Adaptive control is
      necessary because the sensitivity of the patients to sodium nitroprusside varies
      over a wide range. Thirty-three clinical tests during cardiac surgery, including
      the cardiopulmonary bypass phase, were performed. RESULTS: On average the
      controller was in automatic mode for 90.6 +/- 9.6% of the time. The performance
      during automatic control showed the mean arterial pressure to be within 10 mmHg
      of the setpoint for 71.4 +/- 15.5% of the time. The average absolute distance to
      the setpoint was 8.1 +/- 7.2 mmHg. CONCLUSIONS: The overall performance of the
      controller was noted as very satisfactory by the anesthesiologists.

PMID- 9269622
TI  - Template for rapid analysis of the Sonoclot Signature.
AB  - A template was devised for rapid analysis of the intervals, slopes and peak
      amplitude of the Sonoclot Signature.

PMID- 9269623
TI  - pH change in tissue can be detected using infra-red light reflectance
      spectroscopy.

PMID- 9269624
TI  - Alport syndrome--is there a genotype-phenotype relationship?

PMID- 9269625
TI  - Renal function in the elderly--is the dogma of an inexorable decline of renal
      function correct?

PMID- 9269626
TI  - Diabetes and renal failure in Indo-Asians in the UK--a paradigm for the study of
      disease susceptibility.

PMID- 9269627
TI  - Hypertension in haemodialysis patients: is it only hypervolaemia?

PMID- 9269628
TI  - Role of growth factors in acute renal failure.
AB  - EGF, IGF-I, and HGF are involved in the endogenous tissue repair after acute
      renal injury. All three growth factors accelerate the recovery of renal function
      and the anatomical restoration of tubular integrity when given exogenously to
      laboratory animals with experimental ARF. However, clinical study of the
      therapeutic efficacy of recombinant peptide growth factors in ARF is limited to
      rhIGF-I. Both clinical trials of rhIGF-I in patients with ARF have been
      indeterminant or negative. Thus, the therapeutic use of peptide growth factors
      may not be the magic bullet for the cure of a disease that contributes
      significantly to morbidity and mortality in severely ill patients. However, there
      is ample experimental basis for further clinical study of recombinant human
      peptide growth factors in ARF.

PMID- 9269629
TI  - Biologically active peptides in acute renal failure: recent clinical trials.

PMID- 9269630
TI  - Cyclosporin or tacrolimus: which agent to choose?

PMID- 9269631
TI  - New experimental evidence for a role of tissue kallikrein in hypertension.

PMID- 9269632
TI  - The dilemma of evaluating iron status in dialysis patients--limitations of
      available diagnostic procedures.

PMID- 9269633
TI  - Parathyroid hormone gene expression in Hyp mice fed a low-phosphate diet.
AB  - BACKGROUND: The murine analogue of X-linked hypophosphataemia is the Hyp mouse;
      it has chronic phosphate depletion from an inherited defect of renal tubular
      reabsorption. Phosphate directly regulates the parathyroid (PT) in normal rats
      and it is of interest whether this regulation is intact in Hyp mice. METHODS: Hyp
      mice were fed either a low-phosphate diet or control diet and PTH mRNA levels
      were measured. In addition changes in NMR-visible kidney and muscle intracellular
      phosphate potentials in normal and Hyp mice were determined. Mice were maintained
      on a low-phosphate (0.02%) or normal-phosphate (0.6%) diet for 24 and 72 h.
      RESULTS: On the normal diet, Hyp mice had hypophosphataemia, normocalcaemia, and
      normal PTH mRNA levels. Phosphate deprivation for 72 h led to a profound fall in
      plasma phosphate, a slight but significant rise in plasma calcium, and a dramatic
      decrease in PTH mRNA, similar to that of normal mice fed this diet. Changes in
      kidney and muscle intracellular phosphate measured by NMR spectroscopy were not
      affected by diet or genotype. CONCLUSION: Dietary phosphate deprivation decreased
      Hyp mice PTH mRNA levels and caused no change in intracellular phosphate
      potentials. Therefore Hyp mice parathyroids' adapt appropriately to phosphate
      deprivation albeit at a lower threshold compared to normal mice.

PMID- 9269634
TI  - Renal function and oxygen consumption during bacteraemia and endotoxaemia in
      rats.
AB  - BACKGROUND: The hypothesis that renal failure during septic shock may occur as a
      result of hypoxia-related cell dysfunction was investigated in two rat models of
      distributive shock. METHODS: Pentobarbitone-anaesthetized rats received either a
      bolus (1 ml) of living Escherichia coli bacteria (hospital-acquired strain, 1 x
      10(9) CFU/ml; BA-group, n = 7), or a 1-h infusion of endotoxin (E. coli O127.B8:
      8 mg/kg; ET-group, n = 7), or saline to serve as time matched controls (C-group,
      n = 7). RESULTS: Urine flow in the BA- and ET-group reached a nadir at 1 h, but
      thereafter increased and reached values higher than control at 3 h. At this time
      point, renal oxygen delivery had decreased, in the BA-group mainly due to a fall
      in arterial oxygen content and in the ET-group to a fall in renal plasma flow
      (clearance of 131I-hippurate). However, renal oxygen extraction had significantly
      increased, by 31% in the BA and by 59% in the ET group, while renal oxygen
      consumption remained the same. Net tubular sodium reabsorption had decreased by
      55% in the BA and by 25% in the ET group, due to a fall in glomerular filtration
      rate (clearance of creatinine). Hence, an excess oxygen consumption was found
      which was caused neither by an increased renal glucose release nor by the
      presence of an increased number of leukocytes stuck in the glomeruli. Renal
      tubular cells showed normal morphology. An indication that proximal tubular
      function in the BA and ET group remained largely intact were normal ATP levels,
      absence of urinary glucose, and a normal fractional excretion of sodium. However,
      since urine flow had increased in shocked rats at 3 h, water appeared selectively
      lost. CONCLUSIONS: Our data indicate that in rat models of septic shock renal
      failure is not caused by cortical hypoxia or a shortage of cellular energy
      supply.

PMID- 9269635
TI  - Autosomal dominant Alport syndrome linked to the type IV collage alpha 3 and
      alpha 4 genes (COL4A3 and COL4A4).
AB  - BACKGROUND: Alport syndrome is a hereditary nephritis that may lead to end-stage
      renal disease (ESRD) in young adult life and is often associated with
      sensorineural deafness and/or ocular abnormalities. The majority of families are
      X-linked due to mutations in the COL4A5 gene at Xq22. Autosomal forms of the
      disease are also recognized with recessive disease, having been shown to be due
      to mutations in the COL4A3 and COL4A4 genes on chromosome 2. Familial benign
      haematuria has also been mapped to this region in some families. SUBJECTS AND
      METHODS: We describe a large family with autosomal dominant Alport syndrome in
      which males and females are equally severely affected and one member with a mild
      sensorineural deafness reached ESRD aged 35 years. Renal biopsy in four affected
      patients demonstrated characteristic thickened and split glomerular basement
      membranes on electron-microscopy. RESULTS: Genetic linkage analysis using markers
      on chromosome 2q demonstrated co-segregation of the disease with the markers
      D2S351 and D2S401 with a maximum lod score of 3.4 at zero recombination. Linkage
      to the COL4A4 gene was confirmed using an intragenic COL4A4 polymorphism.
      Mutation analysis has revealed a missense Leu36Pro mutation in exon 5 of the
      adjacent COL4A3 gene in the unaffected mother, which may lead to a more severe
      phenotype in affected family members carrying this mutation. CONCLUSION:
      Mutations in the COL4A3 and COL4A4 genes can cause a spectrum of glomerular
      basement membrane disease ranging from autosomal recessive Alport syndrome to
      autosomal dominant Alport syndrome and familial benign haematuria.

PMID- 9269636
TI  - A calcium-channel blocker, amlodipine, attenuates insulin antinatriuresis but
      does not modulate insulin-mediated attenuation of cardiovascular reactivity in
      healthy man.
AB  - BACKGROUND: Insulin exerts an antinatriuretic effect when administered acutely in
      vivo. Interestingly, insulin fails to reduce sodium excretion in rats receiving
      verapamil. The present study was undertaken in order to investigate whether the
      calcium-channel blocker amlodipine attenuates the antinatriuretic effect of
      insulin in humans. METHODS: Eight healthy lean men (32 +/- 2 years) were
      investigated on three different occasions; i.e. time-control, insulin infusion
      alone, and insulin infusion following pretreatment with amlodipine (5 mg x 1
      during 10 days). During the experiments renal haemodynamics (insulin and PAH
      clearances) and segmental tubular sodium handling (sodium and lithium clearances)
      were investigated. The cardiovascular reactivity was also assessed by a graded
      noradrenaline infusion at the end of each experiment. RESULTS: Insulin infusion
      alone was accompanied by a significant 50% reduction in urinary sodium excretion.
      Following amlodipine pretreatment, euglycaemic insulin infusion was associated
      with an attenuated antinatriuretic response and the cumulative sodium excretion
      following 135 min of insulin infusion was significantly higher (24 +/- 4 vs 18 +/
      3 mmol; P < 0.05) as compared to insulin infusion alone. No significant
      differences in the proximal and distal tubular sodium handling respectively, were
      seen following CCB pretreatment. The results also show that the doses of
      noradrenaline required to increase the basal mean arterial blood pressure by 10
      mmHg (262 +/- 38 vs 150 +/- 25 ng/kg/min; P < 0.05) and by 20 mmHg (431 +/- 36 vs
      250 +/- 38 ng/kg/ min; P < 0.05) respectively, were significantly higher during
      the insulin infusion than during the time-control experiment. Pretreatment with
      amlodipine did not further modulate the cardiovascular reactivity. CONCLUSION:
      Pretreatment with a calcium-channel blocker, amlodipine, attenuates the
      antinatriuretic effects of insulin leading to a significantly higher cumulative
      sodium excretion at the end of insulin infusion, which may be of clinical
      importance. Moreover, insulin attenuates the cardiovascular reactivity to a
      graded noradrenaline infusion, suggesting that insulin causes vasodilatation in
      healthy man.

PMID- 9269637
TI  - Renal artery stenosis: evaluation with colour duplex ultrasonography.
AB  - BACKGROUND: Detection of renal artery stenoses (RAS) by means of duplex Doppler
      ultrasound with direct scanning of the main renal arteries is subject to numerous
      limitations. Using semiquantitative analysis of the Doppler curve, which can be
      recorded from intrarenal arteries, it is possible to detect RAS unaffected by the
      problems of direct Doppler scanning of the renal arteries. METHODS: Both
      angiography of the renal arteries and colour duplex ultrasonography (US) of the
      intrarenal vessels (interlobar arteries) were performed in 214 patients (53.2 +/-
      14.1 years) with severe arterial hypertension. Angiography was used as 'gold
      standard' in the diagnosis of RAS and the Doppler results were compared with the
      subsequent findings on angiography. At angiography, the reduction of diameter >
      70% was assessed as haemodynamically effective RAS. For the duplex Doppler
      diagnosis of RAS the following parameters were calculated: (a) resistive index
      (RI) of each kidney, and (b) side-to-side differences of the resistive indices
      (delta RI) between the right and left kidney. RESULTS: Angiography demonstrated
      59 RAS (> 70%) in 53 patients, including six with bilateral RAS. By means of
      duplex US we found a significant difference of RI between kidneys with RAS (0.48
      +/- 0.11) and without RAS (0.63 +/- 0.08; P < 0.001). In addition, a significant
      difference of the delta RI was noted in patients with RAS (24.4% +/- 12.5%) and
      the controls without RAS (3.6% +/- 2.7%). Using a combination of both RI and
      delta RI, threshold values of RI = 0.45 resp. delta RI = 8% yields a sensitivity
      of 92.5% and a specificity of 95.7% in the detection of haemodynamically
      effective RAS. CONCLUSIONS: Colour duplex US with calculation of the RI and delta
      RI of intrarenal arteries is a valuable non-invasive test assessing the
      haemodynamic effects of a RAS. Low costs and safety support the use of the
      Doppler technique in screening for renovascular disease.

PMID- 9269638
TI  - Long-term follow-up of kidney donors: a longitudinal study.
AB  - BACKGROUND: Kidney donors are not adversely affected by compensatory
      hyperfiltration of the remaining kidney in the early years after nephrectomy, but
      longterm longitudinal studies are lacking. METHODS: The renal function and blood
      pressure of 75 donors was evaluated in 1984, 1.4-20.7 years after surgery. Forty
      seven of the original cohort (23 male, age 38-80 years) underwent repeat study a
      decade later (12-31 years post-nephrectomy), using identical laboratory
      techniques. RESULTS: Glomerular filtration rates (GFR) as measured by 51Cr EDTA
      clearance was relatively unchanged a decade later with 41 of 47 subjects (87%)
      having EDTA clearance within the normal laboratory reference range at review. The
      change in GFR in the remaining six subjects was statistically not significant. No
      correlation between GFR and time after nephrectomy was detected. Albumin
      excretion rate (AER), on timed overnight urine collections, was increased (> 20
      micrograms/min) in 16 subjects (34%), although 14 of these individuals were also
      hypertensive. The prevalence of hypertension was significantly increased compared
      with age/sex matched data from epidemiological studies of the general population
      (both in the UK and the US), especially in those over the age of 55 years.
      CONCLUSION: This study demonstrates that the function of the solitary kidney is
      not adversely affected by prolonged compensatory hyperfiltration, although there
      appears to be an increased prevalence of microalbuminuria and hypertension.
      Regular follow-up of kidney donors is recommended in order to manage their
      complications effectively and to detect hypertension and or renal impairment
      early in those who may develop it.

PMID- 9269639
TI  - Abnormal cyanide metabolism in uraemic patients.
AB  - BACKGROUND: We previously investigated the factors involved in uraemic neuropathy
      in patients undergoing regular haemodialysis and found a significant relationship
      between the severity of vibration sensation impairment and the patients' smoking
      habits. The administration of methylcobalamin markedly improved the severity of
      uraemic neuropathy in terms of vibration perception thresholds. We presumed that
      abnormal cyanide metabolism is involved in the development of uraemic neuropathy.
      METHODS: Serum levels of thiocyanate (SCN-), the detoxication product of cyanide,
      were determined in 12 patients with preterminal chronic renal failure (PCRF), 30
      patients undergoing regular haemodialysis (HD patients), and 13 healthy
      volunteers as a control group. Nine of the 30 HD patients were smokers. In
      addition, in 10 HD patients without smoking habits and 10 non-smoking healthy
      volunteers, the proportion of each vitamin B12 analogue in total vitamin B12 was
      estimated. RESULTS: The mean serum SCN- level of the 12 PCRF patients (5.1 +/-
      1.5 micrograms/ml) was significantly higher than that of the control (2.8 +/- 0.9
      micrograms/ml) (P < 0.01). The mean SCN- level before haemodialysis in the 21 non
      smoking HD patients was identical to that in the PCRF group, whereas the level in
      the nine smoking HD patients (7.2 +/- 1.8 micrograms/ml) significantly higher
      than that in the non-smoking subgroup (P < 0.01). In 16 HD patients with
      methylcobalamin treatment, serum SCN- levels were lower than in those without
      methylcobalamin treatment (4.5 +/- 0.5 micrograms/ml in non-smoking subgroup, P <
      0.05). And in the methylcobalamin-treated subgroup (n = 5), the proportion of
      each vitamin B12 analogue in total vitamin B12 was normal. In the untreated
      subgroup (n = 5), the proportion of cyanocobalamin fraction (10.5 +/- 2.6%) was
      as high as the level in Leber's disease patients, while the proportion of
      methylcobalamin fraction was low. And the serum cyanocobalamin level was higher
      in the treated subgroup. CONCLUSION: In uraemic patients, cyanide detoxication
      capability is impaired because of a reduced SCN- clearance, and increased
      cyanocobalamin synthesis indicates elevation of cyanide pool, which would be
      related to the development of uraemic neuropathy. Methylcobalamin was considered
      to be utilized in cyanide detoxication process via cyanocobalamin synthesis.

PMID- 9269640
TI  - Plasma potassium in patients with terminal renal failure during and after
      haemodialysis; relationship with dialytic potassium removal and total body
      potassium.
AB  - BACKGROUND: Chronic haemodialysis (HD) patients may present with severe
      predialysis hyperkalaemia which is improved by dialytic treatment. However,
      factors influencing the behaviour of postdialysis plasma potassium (plasma K) are
      not well known. METHODS: In this prospective study 14 patients (7 female, 7 male)
      on chronic HD were investigated during a standardized 4-h HD with a 2 m2 high
      flux dialyser and up to 6 h postdialysis. Dialytic potassium removal was measured
      by dialysate collection. Total body potassium (TBK) was measured by whole-body
      counting of 40K. RESULTS: Plasma K declined from 5.65 to 3.62 mmol/l on HD. In
      spite of a total dialytic removal of 107 mmol of potassium plasma K rose to 5.01
      mmol/16 h postdialysis. TBK, as adjusted for age, was 38.2 and 49.0 mmol/kg BW in
      female and male patients respectively, i.e. in the normal range. Of a total
      potassium removal of 107 mmol on HD only 42% originated from the extracellular
      space. Dialytic potassium removal was best correlated with removal of
      intracellular potassium but also with extracellular potassium content and with
      the product of plasma K x TBK. The 6-h postdialysis plasma K was correlated with
      the predialysis value but not with TBK or dialytic potassium removal. CONCLUSION:
      A rather high dialytic removal of potassium (which is correlated with plasma K x
      TBK) does not necessarily prevent a rapid postdialysis rebound of plasma K.
      Therefore patients with marked hyperkalaemia should be monitored closely
      postdialysis. TBK can be normal in haemodialysis patients who are well nourished.

PMID- 9269641
TI  - In vitro mitochondrial test to assess haemodialyser biocompatibility.
AB  - BACKGROUND: This paper describes an in vitro mitochondrial test to assess the
      biocompatibility of haemodialysers. METHODS: We tested on isolated liver
      mitochondria the effect of solutions obtained by an aqueous rinse of different
      haemodialysers (cuprophane, cellulose acetate, Hemophan, polyacrylonitrile,
      polymethylmethacrylate, polysulphone, polyamide). Moreover, to determine the
      penetration into the cell and the cytotoxicity of these solutions from
      haemodialysers, we examined the effect of rinse solutions on HT29-D4 cells.
      RESULTS: Our results showed that rinse solutions from haemodialysers decrease the
      mitochondrial ATP synthesis. Cuprophane has the most marked effect, and the
      synthetic membranes exhibited only mild effects. Rinse solutions penetrated the
      cell and were cytotoxic by acting on mitochondria in the cell. In this respect,
      cellulosic membranes were the most toxic. CONCLUSION: Taken together our findings
      lead to a classification of haemodialyser membranes which is identical to one
      based on criteria such as activation of complement (cuprophane > other
      cellulosics > synthetics). Moreover isolated mitochondria make it possible to
      differentiate among the synthetic membranes. Isolated mitochondria thus appear to
      be a good in vitro test to assess the biocompatibility of haemodialysers.

PMID- 9269642
TI  - RenaGel, a novel calcium- and aluminium-free phosphate binder, inhibits phosphate
      absorption in normal volunteers.
AB  - BACKGROUND: Available phosphate binders contain aluminium or calcium which can be
      associated with undesirable effects. RenaGel, cross-linked poly (allylamine
      hydrochloride), is a non-absorbed phosphate-binding polymer, free of calcium and
      aluminium. We conducted this study to examine the safety and phosphate binding
      efficacy of RenaGel in volunteers. METHODS: During 18 days (days 0-17) at the
      clinical study unit, 24 subjects consumed a phosphate-controlled diet designed to
      provide 37.5 mmol (1200 mg) elemental phosphorus per day. From the morning of day
      5 to the morning of day 9, urine and faeces were collected. Average baseline
      urine and faecal phosphorus contents were determined. On days 9-16, the subjects
      received either RenaGel 1 g, 2.5 g, or 5 g or placebo three times per day
      immediately prior to the meals. From the morning of day 13 to the morning of day
      17, urine and faeces were again collected and phosphorus contents on treatment
      were determined. RESULTS: RenaGel inhibited dietary phosphate absorption as
      measured by a decline in average daily urinary phosphorus excretion and an
      increase in average daily fecal phosphorus excretion. Average urine phosphorus
      contents on treatment were 27.2 mmol (870 mg) per day in the placebo group vs
      23.8 mmol (762 mg), 19.5 mmol (625 mg), and 16.6 mmol (530 mg) per day in the
      RenaGel 1-g, 2.5-g, and 5-g groups. Average daily faecal phosphorus content on
      treatment was markedly higher in the RenaGel 5-g group, 19.1 mmol (611 mg) per
      day vs 10.7 mmol (342 mg) per day for the placebo group. RenaGel also decreased
      total serum cholesterol by 0.71 mmol/L (27.5 mg/dl), 0.55 mmol/l (21.3 mg/dl),
      and 1.08 mmol/l (41.8 mg/dl) for the RenaGel 1-g, 2.5-g, and 5-g groups. RenaGel
      was well tolerated with adverse events similar to placebo. CONCLUSIONS: RenaGel
      is a safe, effective, and well tolerated phosphate binder in normal volunteers.
      The degree of phosphate binding consistent with its potential use as a phosphate
      binder in renal failure patients.

PMID- 9269643
TI  - Hepatitis G virus infection in chronic dialysis patients and kidney transplant
      recipients.
AB  - BACKGROUND: The cloning of the hepatitis G virus (HGV), a novel RNA virus of the
      Flaviviridae family, has been very recently developed. HGV is known to be
      parenterally transmitted and has been detected in several patients with
      cryptogenic hepatitis. However, little information exists about the epidemiology
      of HGV infection in renal patients. We studied 178 chronic dialysis patients and
      11 renal transplant individuals to evaluate prevalence, risk factors, and
      clinical manifestations of HGV infection in this population. METHODS: Hepatitis G
      virus infection has been detected by a modified PCR technology which incorporates
      digoxigenin-labelled nucleotides into the amplicon. Primers from the non-coding
      region and the NS-5 region of HGV are utilized for a single round amplification.
      Using a streptavidin surface and a biotin-labelled capture probe, the labelled
      nucleic acid is bound through the capture probe to the surface, and the amplified
      nucleic acid is detected using antibody to digoxigenin. RESULTS: HGV RNA was
      detected in 6% of chronic haemodialysis (HD) patients (11/172), 36% of renal
      transplant recipients (4/11), and 17% (1/6) of patients on peritoneal dialysis
      treatment (CAPD). There were no significant differences between HGV positive and
      negative patients on chronic HD treatment with regard to several demographic,
      biochemical and virological features. However, the frequency of anti-HCV antibody
      was significantly higher in HGV-positive than HGV-negative patients (9/11 (82%)
      vs 51/161 (32%), P = 0.006). In the whole group of HGV RNA-positive patients, 78%
      (11/14) had a history of blood transfusion requirements, 14/16 (87%) had co
      infection with HCV, and 1 (6%) had co-infection with HBsAg. There was no
      significant association between HCV genotypes and HGV RNA positivity. Six (37.5%)
      of 16 HGV RNA-positive patients showed raised aminotransferase values in serum.
      CONCLUSIONS: Patients on maintenance dialysis and kidney transplant recipients
      are at increased risk of HGV infection; HGV is very frequently associated to
      hepatitis C co-infection, regardless of HCV genotype. HGV may be transmitted by
      blood transfusions but transmission routes other than transfusion are possible;
      37.5% of HGV RNA-positive patients showed raised serum aminotransferase levels.
      Further investigations are necessary to clarify the role of HGV infection in the
      development of liver disease in this clinical setting.

PMID- 9269644
TI  - In vivo and in vitro effects of amino-acid-based and bicarbonate-buffered
      peritoneal dialysis solutions with regard to peritoneal transport and
      cytokines/prostanoids dialysate concentrations.
AB  - BACKGROUND: Increasing evidence suggests that conventional PD solutions are
      detrimental to host defence mechanisms of peritoneal cells. We tested a new amino
      acid-based and bicarbonate-buffered PD solution under in vivo and in vitro
      conditions. METHODS: During a prospective, cross-over randomized, intraindividual
      study 10 CAPD patients were investigated with three different solutions:
      Amino/Bic, 1% amino acid, 34 mmol/l bicarbonate; Glu/Bic, 1.5% glucose, 34 mmol/l
      bicarbonate; and Glu/Lac, 1.5% glucose, 35 mmol/l lactate. A PET was performed
      and transport properties (clearance, D/P ratio, MTAC) were calculated. Prostanoid
      and cytokine concentrations were measured in serum and the 6 h effluent. Using an
      in vitro model, mononuclear leukocytes of healthy donors were also incubated with
      the test fluids. In vivo results. Peritoneal clearance and MTAC of small solutes
      (creatinine, urea) were not significantly altered by amino acids or bicarbonate.
      Peritoneal permeability and transperitoneal excretion of higher-weight protein
      molecules (beta 2-microglobulin, albumin, IgG) were increased with Amino/Bic
      compared to Glu/Lac (P < 0.05) (D/P ratio albumin: Amino/Bic, 0.027 +/- 0.003;
      Glu/Bic, 0.023 +/- 0.003; Glu/Lac, 0.022 +/- 0.002). Application of Amino/Bic was
      accompanied by an increased effluent concentration of Il-6, Il-8, TNF alpha,
      PGE2, and 6-keto-PGF1a (P < 0.05). Dialysate nitrite/nitrate and cGMP
      concentrations (as indicators of NO generation) did not differ between the
      solutions. In vitro results. Both bicarbonate fluids demonstrated a better
      preservation of the mitochondrial dehydrogenases activity (MTT assay) compared to
      Glu/ Lac (P < 0.01) (Amino/Bic: 80.6 +/- 3.2%; Glu/Bic: 86.0 +/- 1.8%; Glu/Lac,
      64.9 +/- 2.3%, referred to RPMI as control). Constitutive and LPS stimulated
      release of Il-1 beta and Il-6 was less suppressed with both bicarbonate fluids (P
      < 0.05) (LPS-stim. Il-6 release: Amino/Bic, 33.0 +/- 6.6%; Glu/Bic, 65.5 +/-
      10.3%; Glu/Lac, 1.5 +/- 0.7% referred to RPMI). CONCLUSION: Application of an
      amino-acid/bicarbonate solution resulted in a small but significant increase in
      peritoneal permeability. Also increased concentrations of various
      cytokines/prostanoids were measured in the effluent. According to in vitro
      testing with mononuclear phagocytes both bicarbonate-buffered fluids were to the
      same extent less inhibitory to certain cell functions than lactate-buffered
      solution.

PMID- 9269645
TI  - Initial subcutaneous embedding of the peritoneal dialysis catheter--a critical
      appraisal of this new implantation technique.
AB  - BACKGROUND: The objectives of this open non-randomized study were to evaluate the
      impact of a new peritoneal catheter placement technique on catheter maintenance,
      and complications possibly related to the access, e.g. leakage, infectious
      complications, or drainage failure. METHOD: In a routine clinical setting, a two
      cuff swan-neck catheter was implanted surgically, but its external segment was
      embedded in a subcutaneous pouch initially without exit site to enable
      uncontaminated wound healing and tight ingrowth of the cuffs. After 4 weeks at
      the earliest the distal catheter tip was set free by a small incision under local
      anaesthesia, and CAPD was started. RESULTS: Using this technique, 26 catheters
      were implanted in 17 males and nine females (mean age 52.3 +/- 17.4, range 19-83
      years). The catheters were buried subcutaneously for a median of 79.5 (mean +/-
      SD 132.2 +/- 157.2, range 28-675) days, and were activated in 21 patients. No
      leaks were seen, and only one abdominal wall abscess secondary to a haematoma was
      found. Long-term follow up (mean duration of CAPD 467.0 +/- 338.1, range 32-1320
      days) revealed a very low overall incidence of infectious complications, i.e.
      0.80 per patient-year (1 episode per 14.9 patient-months), and the incidence of
      catheter-related peritonitis amounted to 0.036 per patient-year (1 episode per
      27.2 patient-years), only. However, the postoperative course was complicated by
      seromas in two of 26, and subcutaneous haematomas in 12 of 26 patients, five of
      which were revised surgically. At catheter activation, fibrin thrombi were found
      in nine of 21 patients and two had to be operated. Omental catheter obstruction
      was diagnosed in four patients, and followed by omentectomy. No relationship was
      seen between thrombus formation and omental obstruction and duration of
      subcutaneous embedment (P = 0.27 and P = 0.5 respectively) or patient age (P =
      0.06 and P = 0.13 respectively; Mann-Whitney-test). There was also no
      relationship with primary omentectomy or haematoma. CONCLUSION: We conclude that
      although the very low incidence of infectious episodes favours the new technique,
      further improvement is necessary to decrease the unacceptable rate of
      perioperative complications. Subcutaneous embedding of the catheter may then be
      considered in patients with expected problems of wound healing, and those who
      wish to be prepared for peritoneal dialysis in time.

PMID- 9269646
TI  - Pharmacokinetics of tacrolimus (FK 506) in children and adolescents with renal
      transplants.
AB  - BACKGROUND: Only few data exist on pharmacokinetics of tacrolimus in children.
      PATIENTS: In 1995 and 1996, 14 children (mean age 13 years, range 5-23 years)
      received tacrolimus after renal transplantation; 10 of these after biopsy-proven
      steroid-resistant rejection (2 with vascular rejection), two for cyclosporin A
      (CsA)-induced severe nephrotoxicity, one for untreatable gingival hyperplasia on
      CsA, and one child was treated primarily after transplantation because of severe
      liver involvement in nephronophthisis. Pharmacokinetic investigations were
      performed after establishing a stable maintenance dose with trough levels in the
      desired window of 5-12 ng/ml. RESULTS: Mean follow-up time was 6 months (range 3
      25 months). Eleven patients are still on tacrolimus. Two were discontinued
      because of severe aggravation of chronic persistent hepatitis C (one of them also
      developed diabetes mellitus), and one patient was subsequently switched to
      conventional immunosuppression because of tacrolimus-associated nephrotoxicity.
      All tacrolimus levels were measured by a modified assay (MEIA, Tacrolimus,
      Abbott) with improved sensitivity. At the time of switch, median serum creatinine
      was 234 +/- 82 mumol/l and 6 months after switch 201 +/- 99 mumol/l. All grafts
      are still functioning. Mean FK-506 dose was 0.16 mg/kg body weight/day (range
      0.036-0.30 mg/kg). Mean trough level was 7.1 +/- 2.6 ng/ml in the morning and 6.5
      +/- 2.0 ng/ml in the evening. Median time of maximum concentration (tmax) was 120
      min after application, and the mean maximum concentration (Cmax) was 15.2 +/- 6.7
      ng/ml. Mean area under the curve (AUC) was 104 +/- 33 ng* h/ml, with a range from
      65 yo 169 ng* h/ml. No patient had unsatisfactorily low trough levels during the
      study. There was only a weak but significant (P < 0.05) correlation between dose
      per kg body weight and AUC and, as expected, an excellent correlation (r2 = 0.73,
      P < 0.001) between AUC and trough level. CONCLUSION: Because of interindividual
      variation between patients, therapeutic drug monitoring of tacrolimus is
      mandatory. In this study, a daily dose of 0.15 mg/kg was sufficient in most
      patients. We recommend the performance of at least one pharmacokinetic study
      after establishing stable FK 506 trough levels to ascertain a safe profile.

PMID- 9269647
TI  - Patient survival after renal transplantation; more than 25 years follow-up.
AB  - BACKGROUND: The determinators of patient survival after renal transplantation are
      incompletely known, and conflicting results have been reported. This may have
      been influenced by time-related changes in patient selection, post
      transplantation management and immunosuppressive regimens. This study was
      performed to evaluate in recipients of a first renal transplant the effect of
      patient characteristics, transplantation era, and the immunosuppressive regimen
      on patient survival. METHODS: We used data from the Leiden Renal Transplant
      Database of all first renal transplantations performed between 1966 and 1994 in
      Leiden, the Netherlands. The effect of the following parameters on mortality was
      investigated: era of transplantation, sex, age at transplantation, cause of renal
      failure, immunosuppressive regimen, type and duration of pretransplantation
      dialysis, hypertension, diabetes mellitus, and smoking. In addition we analysed
      the causes of death. Results were expressed as crude mortality rates, relative
      risks of mortality, and standardized mortality ratios as compared with death
      rates in the Dutch population. RESULTS: The analysis comprised 86 living donor
      transplant recipients and 916 cadaver transplant recipients. After adjustment for
      age and sex, the relative risk of mortality for living donor transplant
      recipients compared with cadaver transplant recipients was 0.5 (95% CI 0.2 to
      1.03, P = 0.06). In first cadaver kidney transplant recipients the risk of first
      year mortality improved significantly with time, which coincided with the
      introduction of cyclosporin. The risk of mortality after the first year was
      higher in patients aged over 40 years at transplantation, men, smokers, and in
      the presence of hypertension or diabetes, but the effect of individual factors on
      mortality was small. We found no effect of the type of pretransplantation
      dialysis or the duration of pretransplantation haemodialysis on post
      transplantation mortality. The standardized mortality ratio for recipients of
      first renal transplants was 14 times the population average in the first year
      after transplantation and was still four times in the remaining years.
      CONCLUSION: In the present study, time-related changes in patient management were
      responsible for improved patient survival in the first year after transplantation
      during the study period. Many individual factors contributed moderately to the
      risk of mortality after the first year. Compared to the general population the
      mortality rate of renal transplant recipients was significantly higher during the
      whole follow-up period.

PMID- 9269649
TI  - Effect of haemodynamic variables on surgically created arteriovenous fistula
      flow.
AB  - BACKGROUND: The immediate success and flow rate of a newly constructed
      arteriovenous fistula is dependent on several haemodynamic factors affecting the
      inflow and outflow of the fistula. METHODS: In this study we evaluated the effect
      of preoperative arterial blood pressure, arterial inflow, subclavian venous flow,
      and operative venous outflow resistance on the immediate success, with special
      reference to the quantity of the fistula flow in 32 patients undergoing internal
      arteriovenous fistula operations. Flow measurements were done by utilizing colour
      flow duplex imaging and measurement of venous resistance of the fistula vein was
      accomplished indirectly by a newly developed simple system. RESULTS: A
      preoperative subclavian venous flow rate of less than 400 ml/min was associated
      with higher rate of immediate failures (P < 0.05) with a negative predictive
      value of 100% with 100% sensitivity. Regarding immediate failures, no other
      haemodynamic measurement was found to affect the success of a newly constructed
      fistula significantly. A linear correlation between the measured haemodynamic
      values and the quantity of postoperative fistula flow was not found. However, an
      arterial inflow value of > or = 40 ml/min was associated with higher fistula flow
      rates (P < 0.05). CONCLUSIONS: The immediate success and flow of a newly
      constructed arteriovenous fistula is mainly dependent on arterial inflow and
      subclavian venous flow. An arterial inflow rate of 40 ml/min or more and
      subclavian venous flow rate of 400 ml/min or more measured by colour flow duplex
      imaging prior to the operation will be associated with better outcomes, and
      therefore the use of colour flow duplex imaging is warranted during the
      evaluation of patients who are candidates for an arteriovenous fistula operation.

PMID- 9269648
TI  - The factor V Leiden mutation and risk of renal vein thrombosis in patients with
      nephrotic syndrome.
AB  - BACKGROUND: Acquired abnormalities of coagulation and fibrinolysis in nephrotic
      syndrome have been implicated in the pathogenesis of renal vein thrombosis (RVT).
      Whether resistance to activated Protein C due to a mutation in the gene for
      factor V (FV Leiden/FV506Q, the commonest inherited risk factor for venous
      thrombosis) could contribute to risk of RVT in patients with nephrotic syndrome
      is unknown. METHODS: Genotyping for the factor V Leiden mutation was undertaken
      in a retrospective study of 35 patients with a history of nephrotic syndrome, 10
      of whom had suffered clinically significant and radiologically proven RVT.
      RESULTS: Two patients (6%) were heterozygous for the FV506Q mutation, a
      prevalence similar to studies within the general population. One heterozygote had
      suffered a RVT, whilst the other without a native RVT subsequently had a primary
      renal allograft thrombosis. CONCLUSIONS: In a retrospective study the prevalence
      of the FV Leiden mutation was not increased in patients with nephrotic syndrome
      nor associated with prevalence of clinically significant RVT. Whilst this study
      was insufficiently powerful to fully exclude an association, it suggests acquired
      rather than inherited alterations in the coagulation/fibrinolytic balance
      associated with nephrosis may be of greater importance in venous thrombotic risk,
      and that routine screening of patients with nephrosis for this mutation will not
      identify the majority of patients at risk for RVT. Confirmation of these results
      and determining whether the natural history of thrombosis or underlying renal
      disease in carriers of the FV Leiden mutation differs from those without this
      mutation, will require a large prospective study.

PMID- 9269650
TI  - Central venous catheters for haemodialysis: looking for optimal blood flow.
AB  - Central venous catheters are commonly used for haemodialysis patients and
      represent, in our centre, about 15% of the permanent vascular accesses with a
      total number of more than 230 central venous catheters over the last 10 years.
      Inadequate blood flow may occur and upsets the nurses, the patients, and the
      nephrologist. The aim of this study was to identify the factors of the catheter
      dysfunction. We studied prospectively 25 chronic haemodialysed patients with
      central venous catheters, 14 women and 11 men, 65 +/- 16 (55-89) years of age,
      treated with haemodialysis for 6.7 +/- 7 (1-26) years. Catheters were tunnelled
      silicone twin catheters (Permcath Quinton n = 18, Twincath Hemotec n = 7) in
      right (n = 19) and left internal jugular (n = 6) inserted by percutaneous
      Seldinger techniques. We studied the localization of the catheter tip (superior
      vena cava, right atrium, right ventricular, inferior vena cava), the central
      venous pressure before and after haemodialysis, the blood pressure (BP) before
      and after haemodialysis, the interdialytic weight gain, the number of symptomatic
      hypotensions during the 10 last dialyses. The patients were divided into two
      groups: group I with usual adequate catheter function (n = 18) and group II with
      frequent dysfunctions (n = 7). Central venous pressure before dialysis was
      significantly higher in group I with adequate blood flow and the catheter's tip
      was more frequently found localized in the right cardiac cavities than in the
      vena cava. When central venous pressure before dialysis was over 5 mmHg, no
      dysfunction occurred. Blood pressure was not different between the two groups. We
      found no correlation between central venous pressure and BP, interdialytic weight
      gain and symptomatic hypotensions. We could not predict the central venous
      pressure from the mean BP but there was a higher frequency of hypotensions in the
      hypovolaemic patients. Optimal haemodynamic conditions will be provided by a
      catheter tip in the right cardiac cavities and a central venous pressure over 5
      mmHg which can be provided with vascular filling or dry weight revaluation.

PMID- 9269652
TI  - Exacerbation of lupus nephritis in association with leuprorelin injection for
      uterine leiomyoma.

PMID- 9269651
TI  - Aluminium speciation in cerebrospinal fluid of acutely aluminium-intoxicated
      dialysis patients before and after desferrioxamine treatment; a step in the
      understanding of the element's neurotoxicity.
AB  - BACKGROUND: The association between aluminium and dialysis encephalopathy and
      deterioration of the neurological state during desferrioxamine treatment of
      dialysis patients is well established. At present little is known about the
      speciation and the mechanisms underlying the element's neurotoxicity. METHODS:
      Aluminium speciation was performed in cerebrospinal fluid samples of acutely
      aluminium-intoxicated dialysis patients using a recently developed high
      performance liquid chromatographic/electrothermal atomic absorption spectrometric
      hybrid method. RESULTS: Baseline cerebrospinal fluid aluminium levels of samples
      taken shortly after the intoxication were low but elevated (5.0 +/- 2.0
      micrograms/l, n = 3) as compared to subjects with normal renal function (< 1
      microgram/l). In contrast to the situation noted in serum and to the iron
      speciation in cerebrospinal fluid, aluminium was not bound to transferrin but
      appeared as two distinct compounds, the main fraction eluting at the elution
      volume of aluminium-citrate/silicate. The second compound was not identified.
      Forty-four hours after desferrioxamine administration the cerebrospinal fluid
      aluminium levels had increased up to a concentration of 10.3 +/- 2.5 micrograms/l
      (n = 3). This was accompanied by a change in the speciation profile with
      aluminium appearing at the elution volume of aluminoxamine. CONCLUSIONS: Our
      findings may contribute to a better understanding of the neurotoxic effects of
      aluminium and its desferrioxamine chelate in dialysis patients.

PMID- 9269653
TI  - Retroperitoneal lymphangiectasia associated with bilateral renal vein thrombosis.

PMID- 9269654
TI  - Relapsing polychondritis and myelodysplasia.

PMID- 9269655
TI  - Marfan syndrome presenting with transient renal insufficiency.

PMID- 9269656
TI  - Thoracic aortic dissection complicating autosomal dominant polycystic kidney
      disease.

PMID- 9269658
TI  - Captopril hepatotoxicity in a case of renal crisis due to systemic sclerosis.

PMID- 9269657
TI  - Vascular renal AA amyloidosis in adult Still's disease.

PMID- 9269659
TI  - Cutaneous scleroderma following bilateral arteriovenous fistula formation.

PMID- 9269660
TI  - Type III mixed cryoglobulinaemia in the course of Hantavirus nephropathy.

PMID- 9269661
TI  - The febrile patient presenting with acute renal failure and enlarged kidneys-
      another mode of presentation of malakoplakia.

PMID- 9269662
TI  - Prolonged treatment with granulocyte colony-stimulating factor in a patient with
      Felty's syndrome and chronic renal failure from secondary amyloidosis.

PMID- 9269663
TI  - Aeromonas hydrophila necrotizing fasciitis and gas gangrene in a diabetic patient
      on haemodialysis.

PMID- 9269664
TI  - Permanent pacemaker wires causing subclavian vein stenosis in presence of AV
      fistula--is it ever wrong to try angioplasty and stenting?

PMID- 9269665
TI  - Appearance of multiple progressive nodules in the spleen of a renal graft
      recipient.

PMID- 9269666
TI  - Renal transplantation from a donor with a nail-patella syndrome.

PMID- 9269667
TI  - Transient hyperphosphatasaemia in a 4-year-old boy after successful kidney
      transplantation.

PMID- 9269668
TI  - Kaposi sarcoma and gonadoblastoma dysgerminoma with gonadal dysgenesis following
      cadaveric renal transplantation.

PMID- 9269669
TI  - Ethyleneglycol intoxication in a dipsomaniac patient.

PMID- 9269670
TI  - The lady seen for evaluation of left flank pain and a 'small left kidney'.

PMID- 9269671
TI  - Water bewitched.

PMID- 9269672
TI  - Ureteral stenosis in Wegener's granulomatosis.

PMID- 9269673
TI  - A renal disease frequently found at postmortem, but rarely diagnosed in vivo.

PMID- 9269674
TI  - Impact of the method of calculation on assessment of the parathyroid hormone
      calcium set point.

PMID- 9269675
TI  - Pruritus and skin hydration during dialysis.

PMID- 9269676
TI  - Antiviral treatment for HCV patients pre-renal transplantation?

PMID- 9269677
TI  - The BsmI vitamin D-receptor polymorphism and secondary hyperparathyroidism.

PMID- 9269679
TI  - End-stage renal disease due to Bardet-Biedl syndrome.

PMID- 9269678
TI  - Reduced proteinuria after cessation of long-acting, osmotic release nifedipine
      GITS in diabetic nephropathy.

PMID- 9269680
TI  - An experience of the therapeutic use of an endotoxin adsorption column for
      microangiopathic haemolytic uraemic syndrome.

PMID- 9269681
TI  - Increase in the incidence of analgesic nephropathy in Hungary.

PMID- 9269682
TI  - Heterozygosity for factor V Leiden in a haemodialysis patient with recurrent
      shunt thrombosis.

PMID- 9269683
TI  - Antisense against protein kinase C-alpha mRNA makes sense for cancer therapy?

PMID- 9269684
TI  - Cytotoxic T cells head for the clinic?

PMID- 9269685
TI  - A molecular injury-response model for the understanding of chronic disease.
AB  - Over the past century, modern medicine has been remarkably effective in managing
      acute diseases. However, medical paradigms have been less successful in the
      understanding and treatment of chronic inflammatory and degenerative disorders
      such as multiple sclerosis, connective-tissue disorders, chronic infections and
      chronic transplant rejection. Despite significant advances in biology over the
      past two decades, much of this knowledge has yet to be translated to medical
      practice. In this article, we propose a new framework for chronic disorders that
      could aid in the correlation of molecular, cellular and clinical data, leading to
      more rational treatments.

PMID- 9269686
TI  - The blood-brain barrier and the inflammatory response.
AB  - The environment of the brain is controlled by a sophisticated endothelial barrier
      that prevents the free entry of solutes from the blood. It is commonly assumed
      that this blood-brain barrier (BBB) also prevents the entry of leukocytes into
      the central nervous system. However, recent evidence in animal models shows that
      this is not the case, and leukocytes can cross an intact BBB during health and
      disease. Indeed, in many neurological diseases, including Alzheimer's disease,
      prion diseases and AIDS-related dementia, leukocytes enter the brain parenchyma
      without concomitant BBB breakdown. Current research is concentrating on factors
      that control the integrity of the BBB and the mechanisms that leukocytes use to
      enter the brain.

PMID- 9269687
TI  - Serological analysis of human tumor antigens: molecular definition and
      implications.
AB  - Specific vaccines for the immunotherapy of human neoplasms require specific human
      tumor antigens. While efforts to identify such antigens by the analysis of the T
      cell repertoire have yielded few antigens, the application of SEREX, the
      serological identification of antigens by recombinant expression cloning, has
      brought a cornucopia of new antigens. Several specific antigens have been
      identified in each tumor tested, suggesting that many human tumors elicit
      multiple immune responses in the autologous host. The frequency of human tumor
      antigens, which can be readily defined at the molecular level, facilitates the
      identification of T-cell-dependent antigens and provides a basis for peptide and
      gene-therapeutic vaccine strategies.

PMID- 9269688
TI  - Establishing chemoresistance in hematopoietic progenitor cells.
AB  - An attractive approach to circumvent chemotherapy-induced myelosuppression is the
      use of gene-transfer technology to introduce new genetic material into
      hematopoietic cells. Several pre-clinical studies have demonstrated that
      increasing the expression of genes encoding proteins that modulate drug
      resistance in hematopoietic cells provides significant protection against
      chemotherapy-induced myelosuppression both in vitro and in vivo. Most work in
      this area has focused on the use of recombinant retroviruses as vectors for the
      delivery of DNA sequences into hematopoietic stem cells and progenitor cells.
      Based on these studies, clinical trials are now under way to evaluate the
      potential use of two gene sequences-multidrug resistance gene 1 and O6
      methylguanine DNA methyltransferase. Reducing chemotherapy-induced
      myelosuppression by increasing the expression of genes that modulate drug
      resistance via gene transfer into bone marrow cells might allow dose
      intensification of chemotherapy, which might result in an improvement in the
      clinical outcome of patients with high-risk tumors.

PMID- 9269689
TI  - Genetic prodrug activation therapy.
AB  - Genetic prodrug activation therapy shows promise as a therapeutic option for the
      treatment of cancer as well as a variety of other diseases. It involves the
      insertion of a gene encoding a drug-metabolizing enzyme into cells and the
      systemic administration of a prodrug. The prodrug is converted to a cytotoxic
      agent by the action of the expressed enzyme. To ensure that the enzyme is only
      expressed in the targeted subset of cells, the transcriptional apparatus of a
      gene that is unique to this subset is used to regulate the gene encoding the drug
      metabolizing enzyme. As with all types of gene therapy, one of the major
      obstacles to successful clinical treatment is the development of safe and
      effective gene delivery systems.

PMID- 9269690
TI  - Microalbuminuria as risk in essential hypertension.

PMID- 9269691
TI  - Detecting microalbuminuria by urinary albumin/creatinine concentration ratio.
AB  - BACKGROUND: Microalbuminuria, i.e. a subclinical increase of the albumin
      excretion rate in urine, may be a novel atherosclerotic risk factor. This study
      aimed to test whether microalbuminuria can be identified by measurement of
      urinary albumin concentration or urinary albumin/creatinine concentration ratio,
      instead of the usual measurement of the albumin excretion rate in a timed urine
      collection. METHODS: All 2579 subjects analysed were screened in a population
      based epidemiological study. Participants with diabetes mellitus, renal disease,
      haematuria, or urinary tract infection were not included. Urinary albumin (Ualb)
      and creatinine (Ucreat) concentrations were measured in an overnight collected
      sample by enzyme-linked immunosorbent and colorimetric assays, respectively.
      Urinary albumin excretion rate (UAER) and urinary albumin/creatinine
      concentration ratio (Ualb/Ucreat) were calculated. RESULTS: The correlation
      between Ualb and UAER was 0.72 (n = 2579, P < 0.001), and the correlation between
      Ualb/Ucreat and UAER was 0.81 (n = 2579, P < 0.001). In the detection of
      microalbuminuria, the nosographic sensitivity and specificity, and the diagnostic
      specificity were 58%, 97%, and 66% for Ualb, and 73%, 97%, and 73% for
      Ualb/Ucreat, respectively. CONCLUSIONS: It is concluded that measurement of the
      albumin/creatinine concentration ratio is a specific and quite sensitive
      alternative to measurement of the urinary albumin excretion rate in timed
      collections, when screening for microalbuminuria.

PMID- 9269692
TI  - Proteinuria and progressive renal disease: birth weight and microalbuminuria.
AB  - BACKGROUND: Microalbuminuria and nephropathy in diabetic subjects has been linked
      to low birth weight or short stature in adulthood. We have explored the
      relationship of foetal growth and intrauterine starvation with microalbuminuria
      in non-diabetic subjects. METHODS: Albumin excretion rate was measured in an
      overnight sample in 236 men and women in Preston whose birth anthropometry had
      been recorded at the local maternity hospital. Albumin excretion rate was also
      measured in a 2-h and overnight sample in 98 subjects exposed to intrauterine
      maternal starvation during the Siege of Leningrad as well as in 124 subjects
      exposed in infancy and 62 born concurrently outside the Siege limits. RESULTS: In
      236 men and women aged 46-54 years in Preston, 11 had microalbuminuria on an
      overnight urine collection. There were trends for these subjects to have lower
      birth weight (105.8 oz vs. 112.9 oz, P = 0.20) and lower ponderal index at birth
      (12.3 oz/in3 x 1000 vs. 13.4 oz/in3 x 1000, P = 0.09) than those who were
      normoalbuminuric. The albumin excretion rate of the subjects exposed in utero to
      maternal starvation (daytime sample 5.2 x/divided by 2.8 micrograms.min-1;
      overnight sample 2.9 x/divided by 2.5 micrograms.min-1) was not significantly
      different from those of the subjects exposed in infancy (5.5 x/divided by 2.7
      micrograms.min-1 and 3.3 x/divided by 2.5 micrograms.min-1, respectively) or from
      those who were unexposed (5.1 x/divided by 3.0 micrograms.min-1 and 3.2 x/divided
      by 2.2 micrograms x min-1, respectively), (P = 0.99 for daytime and P = 0.73 for
      overnight rates controlling for sex, BMI, and systolic blood pressure).
      CONCLUSIONS: Consistent relationships of short stature with microalbuminuria and
      nephropathy in non-diabetic and diabetic subjects might suggest that more subtle
      anthropometric indices could relate to low nephron number at birth, or that
      postnatal or genetic influences could underlie the observed link.

PMID- 9269693
TI  - Endothelium-dependent vasodilatation and distensibility of large arteries in
      chronic haemodialysis patients.
AB  - BACKGROUND: Cardiovascular mortality is increased in chronic haemodialysis (HD)
      patients and is not completely explained by common cardiovascular risk factors.
      Hyperhomocysteinaemia and chronic HD per se may play a role, because these
      factors may adversely affect endothelial function and distensibility of conduit
      arteries, which are important determinants of the risk of atherosclerosis,
      thrombosis and cardiac hypertrophy. METHODS: A vessel wall movement detector
      system was used to investigate endothelium-dependent, flow-mediated and
      endothelium-independent, glyceryl trinitrate-induced vasodilatation in the
      brachial artery and compliance and distensibility coefficients (CC and DC) in the
      common carotid artery in 28 chronic HD patients and 28 control subjects. RESULTS:
      Endothelium-dependent, but not endothelium-independent, vasodilatation was
      markedly reduced in the HD group (3.7 +/- 1.1 vs. 9.7 +/- 1.2%; P = 0.001). The
      DC was reduced only in a subgroup of patients aged < 50 years: 16.9 +/- 1.5 vs.
      22.4 +/- 2.0 10(-3)/kPa (P = 0.032) and was not related to endothelium-dependent
      vasodilatation. CC did not differ between the groups. Plasma total homocysteine
      was elevated in the HD patients, but was neither related to endothelium-dependent
      vasodilatation, nor to DC. CONCLUSION: Chronic renal failure and (or) chronic
      haemodialysis are associated with impaired endothelium-dependent vasodilatation,
      which may reflect an increased susceptibility for the development of
      atherosclerosis and thrombosis.

PMID- 9269694
TI  - Losartan reduces albuminuria in patients with essential hypertension. An
      enalapril controlled 3 months study.
AB  - BACKGROUND: Elevated urinary albumin excretion is a common feature of essential
      hypertension which may be reduced by ACE-inhibition through independent
      reductions of both systemic and intraglomerular pressure. A concurrent inhibition
      of bradykinin breakdown may be involved. METHODS: A double-blind, randomized, 12
      weeks study of the effects on enalapril 20 mg (n = 46) vs losartan 50 mg daily (n
      = 47) on blood pressure, albuminuria, fasting blood glucose, and lipids in 57
      male and 36 female patients with essential hypertension. RESULTS: Blood pressure
      was similarly reduced during both treatments: enalapril 156/102 (15/5) (mean [SD]
      to 142/92 [14/7]) mmHg, losartan: 159/103 (17/6) to 149/94 (21/9) mmHg, both P <
      0.001. Urinary albumin to creatinine ratio was significantly reduced during
      losartan (from 1.14(x/divided by 2.48) (geometric mean (x/divided by antilog SD)
      to 0.81 (x/divided by 2.43) mg/mmol, P < 0.01), as well as during enalapril (from
      0.95 (x/divided by 2.45) to 0.73 (x/divided by 2.00) mg/mmol, both P < 0.05). The
      effect on albuminuria was especially evident in patients with microalbuminuria.
      Fasting blood glucose, total cholesterol, HDL-cholesterol and triglycerides were
      unchanged during losartan, whereas minor reductions were found in all lipids
      during enalapril. No difference was observed between the groups. CONCLUSION:
      Enalapril 20 mg and losartan 50 mg daily reduce blood pressure equally in
      essential hypertensive patients. No adverse effects were seen on glucose and
      lipid concentrations. Losartan treatment reduces albuminuria at least as
      effectively as enalapril, suggesting that glomerular leakage of albumin is
      profoundly affected by the effects angiotensin II.

PMID- 9269695
TI  - Risk factors for development of diabetic nephropathy: a review.
AB  - Recently evidence has accumulated that diabetic nephropathy clusters in families,
      both in insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic
      patients. Furthermore, hypertension and cardiovascular accidents are found more
      frequently in families of NIDDM with diabetic nephropathy. Some observations in
      offspring of NIDDM patients with diabetic nephropathy point to high urinary
      albumin excretion and slightly greater blood pressure values, both within the
      normal range compared to offspring of patients without diabetic nephropathy.
      Further follow-up is required to assess whether these findings are indicative of
      a possible genetic predisposition to diabetic nephropathy.

PMID- 9269696
TI  - Vessel wall heparan sulfate and transcapillary passage of albumin in experimental
      diabetes in the rat.
AB  - BACKGROUND: To investigate whether albuminuria in streptozotocin-induced diabetes
      mellitus in the rat is a symptom of a more generalized vessel wall permeability,
      and whether changes in vessel wall heparan sulfate (HS) are associated with
      alterations in vessel wall permeability. METHODS: The transcapillary escape rate
      of albumin (TERalb) was calculated from the disappearance rate from the
      circulation of i.v. injected radiolabeled albumin, together with the regional
      clearance of albumin (RCalb) in several tissues using a double isotope technique.
      These measurements were performed in seven rats one year after diabetes induction
      and in seven sex- and age-matched control rats. To evaluate the association
      between vessel wall HS and the transcapillary passage of albumin, we determined
      the content of basement membrane HS in tissue homogenates of heart, liver,
      kidneys, and lungs with a sensitive inhibition-ELISA using a monoclonal antibody
      (JM-403), which specifically recognizes basement membrane HS. RESULTS: Diabetic
      rats developed albuminuria (31.7 +/- 10.8 mg/24 h) in contrast to control animals
      (2.2 +/- 1.5 mg/24 h; P = 0.0006). TERalb was increased from 13.3 +/- 1.7 in
      control rats to 15.6 +/- 2.6%/h in diabetic rats, P = 0.02. RCalb was
      significantly increased in heart, liver, skeletal muscle and aorta, unchanged in
      kidneys and skin, and significantly decreased in lung tissue. We found a decrease
      in HS content in heart tissue of diabetic rats, and a correlation between HS
      content and RCalb (r = -0.72, P = 0.004), in contrast with an increase in lung HS
      content that correlated with a decrease in RCalb (r = -0.64, P = 0.014). No
      changes in HS content were found in kidney and liver tissue. CONCLUSIONS: These
      data indicate that in one-year diabetic rats albuminuria coincides with an
      increased TERalb and RCalb in most, but not all tissues, and that alterations in
      basement membrane HS content correlate with changes in the RCalb, which suggests
      a functional relationship.

PMID- 9269697
TI  - The relationship between microalbuminuria in first generation diabetic and non
      diabetic subjects and microalbuminuria and hypertension in the second generation
      (a population based study).
AB  - BACKGROUND: Predisposition to hypertension has been proposed as a risk factor for
      development of diabetic nephropathy and hypertension. The aim of this study was
      to examine a possible relation between microalbuminuria (urinary albumin
      excretion (UAE) 20-200 micrograms/min) in diabetic and non-diabetic subjects and
      microalbuminuria as well as hypertension in the next generation. METHODS: We
      examined 280 non-diabetic subjects in a cross sectional study (mean age 47-48
      years). 136 were first born offspring of non insulin dependent diabetic (NIDDM)
      patients and 144 were first born offspring of non-diabetic controls. Hypertension
      was defined as systolic blood pressure > 140 mmHg, and/or diastolic blood
      pressure > 90 mmHg, and/or the presence of antihypertensive medications. Data
      were analysed by multiple logistic regression. RESULTS: We found that parental
      microalbuminuria was not predictive for microalbuminuria in the second generation
      in this population at the time of follow-up. However, microalbuminuria was
      predictive for hypertension in the second generation of diabetic patients, Odds
      ratio (OR) = 2.5, P = 0.05 when adjusted for age, gender, smoking, and obesity.
      In offspring of non-diabetic persons parental microalbuminuria also increased the
      risk of hypertension in the offspring generation, OR = 3.7, P = 0.02. Obesity was
      the strongest predictor for microalbuminuria and for hypertension in offspring of
      diabetic patient and of non-diabetic persons. CONCLUSION: We found a significant
      relation between microalbuminuria in the parental generation and hypertension in
      the offspring both of a diabetic population and of a non-diabetic population.

PMID- 9269698
TI  - Angiotensin I converting enzyme gene polymorphism and diabetic nephropathy in
      type II diabetes.
AB  - BACKGROUND: The factors leading to diabetic nephropathy (DN) are not completely
      understood. Besides glycaemic control, genetic predisposition seems to play an
      important role for the development of DN. Genes of the renin-angiotensin system
      are potential candidate genes. An insertion/deletion polymorphism in the gene
      coding for the angiotensin I converting enzyme (ACE) has been extensively
      examined, but results were conflicting. METHODS: We studied 658 patients with
      type II diabetes (n = 347 without DN, n = 311 with DN). RESULTS: No difference
      was found in genotype distribution or allele frequencies between diabetic
      patients with and without nephropathy as defined by albumin excretion > or = 30
      mg/day, but patients on dialysis had more frequently the DD-genotype. CONCLUSION:
      Although we acknowledge certain problems in the design of the study the results
      in this large cohort suggest that the I/D polymorphism of the ACE gene does not
      play a major role in the development of DN. They are compatible, however, with a
      role of the gene in progression.

PMID- 9269699
TI  - ACE polymorphism does not determine short-term renal response to ACE-inhibition
      in proteinuric patients.
AB  - BACKGROUND: The renal response to ACE inhibition is known to vary between
      individuals. The ACE genotype is a determinant of the ACE concentrations in
      plasma and tissue, and therefore might affect the renal response to ACE
      inhibition in renal patients. METHODS: To test this hypothesis we studied the
      short-term response to ACE inhibition (enalapril or lisinopril 10/20 mg/d) in 61
      stable proteinuric patients (> 1.0 g/day) in relation to the ACE genotype (DD N =
      16, ID N = 32, II N = 13). RESULTS: Baseline values were not significantly
      different for the three groups. ACE inhibition significantly reduced proteinuria,
      mean arterial pressure, GFR and FF in all genotype groups. The reduction in
      proteinuria, MAP, GFR and FF was not different between the genotype groups. ERPF
      increased significantly and to the same extent in all three groups. CONCLUSIONS:
      We conclude that in proteinuric patients the short-term responses to ACE
      inhibition of proteinuria, blood pressure, and renal haemodynamics are not
      determined by ACE genotype. Thus, ACE gene polymorphism does not account for the
      known interindividual variation in the short-term renal response to ACE
      inhibition.

PMID- 9269700
TI  - Spectrum of diurnal rhythms in glomerular permeability in patients with
      membranous nephropathy.
AB  - BACKGROUND: Diurnal rhythms in proteinuria and selectivity index (SI) of
      proteinuria can vary from patient to patient with respect to phase and amplitude
      (A/M) and in some cases rhythms are absent. The aim of the present study was to
      relate this variability to a different pattern of diurnal rhythms in
      permselectivity of the glomerular capillary wall (GCW). METHODS: Ten patients
      with nephrotic syndrome due to membranous nephropathy were studied. Diurnal
      rhythmicity in size-dependent permselectivity of the GCW was determined by
      measuring 3-h fractional clearances of dextrans (30-90 A) over a period of 1 day.
      RESULTS: Four types of rhythmicity could be recognized. Type I and II only
      differed in the magnitude of the diurnal variability in glomerular transport
      through large pores (r2) and shunt pathway (omega). Both had normal rhythms in
      clearance of proteins and SI, but all rhythms were more pronounced in the
      patients with normal renal function and mild histological abnormalities (type
      II). Although type III also had a normal GFR and minor histological lesions, only
      transport through omega (and not through r2) showed a significant diurnal rhythm,
      which implied that this type did not have a normal rhythm in SI. The patients
      with advanced renal failure and extensive interstitial lesions neither had a
      rhythm in permselectivity nor had normal rhythms for proteinuria and SI (type
      IV). CONCLUSIONS: The type of rhythmicity in glomerular permeability corresponds
      well with the presence and phase of rhythms in clearance of proteins and in SI of
      the proteinuria.

PMID- 9269701
TI  - Is the antiproteinuric response to inhibition of the renin-angiotensin system
      less effective during the night?
AB  - BACKGROUND: In glomerular disease proteinuria usually has a circadian pattern
      with maximum excretion during the day. Blockade of the renin-angiotensin system
      (RAS) results in a 50% reduction of proteinuria as measured in 24-h urine
      collections. We questioned whether anti-proteinuric treatment by blockade of the
      RAS is as effective during the day as during the night. METHODS: We analysed data
      from two intervention studies on proteinuria in patients with non-diabetic renal
      disease. In the first study, six hospitalized patients (proteinuria 5.8 +/- 2.9
      g/day) were treated with the renin-inhibitor remikiren 600 mg o.d. during 8 days.
      In the second study eight ambulant patients (proteinuria 7.5 +/- 2.7 g/day) were
      treated during 6 weeks with the ACE-inhibitor trandolapril 4 mg o.d. Urine was
      collected in a day- and in a night-time portion. RESULTS: Daytime proteinuria
      declined from 0.29 +/- 0.15 to 0.22 +/- 0.11 g/h (P < 0.05) during remikiren and
      from 0.33 +/- 0.14 to 0.16 +/- 0.08 g/h (P < 0.05) during trandolapril. Night
      time proteinuria, however, was not significantly reduced from 0.23 +/- 0.11 to
      0.19 +/- 0.11 g/h during remikiren and from 0.29 +/- 0.17 to 0.20 +/- 0.12 g/h
      during trandolapril. Both interventions effectively lowered blood pressure during
      the day as well as the night. CONCLUSION: In both studies relative nocturnal
      therapy resistance to the antiproteinuric effect of RAS blockade was found,
      despite 24-h efficacy of blood pressure effect. This may have clinical relevance
      because it contributes to rest-proteinuria and thus may affect long term renal
      function outcome. It may be worthwhile to explore alternative therapeutic
      regimens to improve the nocturnal antiproteinuric response.

PMID- 9269703
TI  - Prevention of progression of nephropathy.
AB  - Several factors have been implicated in progressive nephropathy. In a recent
      clinical trial, the Modification of Diet in Renal Disease (MDRD) study, six
      factors out of 41 examined were found to be predictors of progression of renal
      disease: proteinuria, mean arterial pressure, black race, diagnosis of polycystic
      kidney disease, serum transferin levels, and serum high density lipoprotein (HDL)
      cholesterol. Hypertension as a factor in progressive renal disease has been
      documented in both animal and human studies. Patients in the MDRD study were
      randomly assigned to two levels of blood pressure control: usual (mean arterial
      pressure of 107 mmHg) or low (mean arterial pressure of 92 mmHg). Patients with
      proteinuria > 1 g/day assigned to the low blood pressure goal had a slower mean
      decline in GFR as compared to patients assigned to the usual blood pressure goal.
      Recommendations derived from the results of the MDRD study specify that in
      patients with proteinuria > 1 g/day, a mean arterial pressure goal of 92 mmHg or
      less (equivalent to a blood pressure of 125/75 mmHg) should be the target.
      Several studies have suggested that dietary protein restriction benefits patients
      with chronic renal disease. The MDRD study found that dietary protein restriction
      slowed disease progression in patients with more advanced renal disease (GFR 13
      24 ml/min) at the onset of the trial. In summary, current evidence indicates that
      a decrease in proteinuria, lowering of systemic blood pressure, and a decreased
      intake of protein ameliorate the rate of progression (loss of GFR) in patients
      with chronic renal disease.

PMID- 9269702
TI  - Measurement of glomerular charge selectivity in non-diabetic renal disease.
AB  - BACKGROUND: Until now, the renal clearance index of IgG to IgG4 (IgG/IgG4) as
      well as pancreatic to salivary amylase (PA/SA) were separately used as parameters
      of renal charge selectivity in diabetic and non-diabetic albuminuria. The
      suitability of the IgG index may be questioned because urinary loss of IgG rather
      reflects a size selective defect. In contrast, the amylase index seems more
      appropriate to reflect renal charge selectivity because its molecular size is
      comparable to albumin. We questioned whether IgG/IgG4 and PA/SA reflect renal
      charge selectivity in a comparable way in subjects with non-diabetic albuminuria
      over a wide range. METHODS: Renal fractional clearances of albumin, IgG, IgG4, PA
      and SA were estimated from ambulatory 24-h urine samples in 12 subjects with
      normo-albuminuria (UAE 4 [3-17] micrograms/min), six with micro-albuminuria (UAE:
      147[36-200] micrograms/min), and 20 with macro-albuminuria (UAE: 2301 [608-13611]
      micrograms/min). RESULTS: Macro-albuminuria is associated with a reduced IgG/IgG4
      and PA/SA, whereas micro-albuminuria is only associated with a reduced IgG/IgG4
      compared to normo-albuminuria. A reduction of IgG/IgG4 (r = -0.75, P < 0.001) and
      PA/SA (r = -0.52, P < 0.001) correlates with an increased albuminuria. In
      addition, IgG/IgG4 correlates with PA/SA in the total population (r = 0.49, P <
      0.01). IgG/IgG4 (r = 0.51, P < 0.05) correlates with the size selective index
      IgG/albumin in an opposite way to PA/SA (r = -0.52, P < 0.05) in 20 subjects with
      macro-albuminuria. Multiple regression analysis revealed IgG clearance to be the
      variable which contributes to the variance of albuminuria clearance for the
      greater part in our population. CONCLUSION: Both charge selective indices do not
      appear to correlate in micro-albuminuria. In addition, the presence of a size
      selective defect has a opposing effect on both charge selective indices. Although
      the reduction of IgG/IgG4 and PA/SA with increasing albuminuria suggests a
      progressive charge selective defect, albuminuria in our population is almost
      entirely explained by urinary loss of IgG. These data seriously question whether
      either one or both charge selective indices IgG/IgG4 and PA/SA do specifically
      reflect glomerular charge selectivity.

PMID- 9269704
TI  - Deletion insertion polymorphism of the angiotensin converting enzyme gene and
      progression of diabetic nephropathy.
AB  - BACKGROUND: The activity in the renin angiotensin system is important for the
      progression of diabetic nephropathy. Genetic abnormalities in this system have
      been suggested as a risk factor for the development and progression of diabetic
      nephropathy. The homozygous DD (deletion) genotype of the angiotensin-converting
      enzyme gene has been associated with increased circulating angiotensin converting
      enzyme and a more rapid progression of IgA nephritis. The aim of the present
      study was to investigate the relationship between the DD genotype and rate of
      decline in kidney function in patients with type 1 diabetes and nephropathy in
      relation to other risk factors for loss of renal function. METHODS: The insertion
      deletion polymorphism was determined in patients with type 1 diabetes mellitus
      and diabetic nephropathy. Retrospective data were collected in 86 patients. The
      patients were studied by determining glomerular filtration rate during a mean (+/
      SD) of 8.5 +/- 4.0 years (range 1.3-14.5 years) using the clearance of 51Cr EDTA.
      Measurements for glycaemic control, urinary albumin excretion, blood pressure,
      and serum lipids were available for the study period. RESULTS: The mean decline
      in glomerular filtration rate was 3.2 +/- 3.6 ml/min/year in all patients.
      Patients with the DD, ID and II genotype showed a rate of change in glomerular
      filtration of -3.5 +/- 3.5, -3.1 +/- 4.4 and -2.6 +/- 2.3 ml/min/year
      respectively. The tendency towards a more rapid decline in kidney function in the
      DD genotype was nonsignificant. The decline in renal function was significantly
      correlated to systolic and diastolic blood pressure, Hb AIc and serum
      triglycerides. Serum cholesterol was nearly significantly correlated to the
      decline in glomerular filtration rate (P = 0.057). Of these variables, glycaemic
      control and blood pressure control remained significant in multivariate analysis
      (P = 0.02 and P = 0.04, respectively). The patients with the DD genotype weighted
      significantly less. The body weight in patients with the DD genotype was 67.1 +/-
      11.4 kg vs 74.9 +/- 9.2 kg in patients with the II genotype (P = 0.018).
      CONCLUSION: In this study, poor glycaemic and blood pressure control were
      associated with a more rapid loss of renal function in diabetic nephropathy while
      polymorphism of the angiotensin converting enzyme gene was not.

PMID- 9269705
TI  - Promoters of progression of diabetic nephropathy: the relative roles of blood
      glucose and blood pressure control.
AB  - BACKGROUND AND AIMS: Hyperglycaemia is a strong risk factor for the development
      of renal disease in insulin dependent diabetes mellitus but it is uncertain
      whether it contributes to the progression of incipient or established
      nephropathy. The rigorous treatment of blood pressure in recent years may help
      uncover the contribution of hyperglycaemia, if any, to the progression of renal
      failure. Our aim therefore, was to assess in a current cohort of insulin
      dependent diabetic patients with diabetic nephropathy the relative importance of
      glycaemic control and blood pressure on disease progression. METHODS: All insulin
      dependent diabetic patients with persistent albuminuria (> 300 mg/24 h) attending
      the diabetic clinic at Guy's Hospital between 1977 and 1993 were recruited.
      Serial measurements of blood pressure, HbA1 and GFR were performed every 6 months
      until end-stage renal disease or death. Only patients with at least 1 year of
      follow up were analysed. The mean follow up period was 8 years (range 1.5-15.5
      years). Baseline and time dependent variables were related to the rate of change
      of GFR using weighted linear regression and stepwise multiple regression
      analysis. The impact of each variable on the change of GFR with time was adjusted
      for the effect of other potentially confounding variables by analysis of co
      variance. RESULTS: Patients had well-controlled blood pressure throughout the
      observation period (mean arterial pressure 97 +/- 8 mmHg) and the average rate of
      decline of GFR was 4.32 +/- 4.08 ml/min/year. In univariate analysis baseline and
      mean HbA1 were linearly related to the rate of decline of GFR (baseline r5-0.565,
      P < 0.001; mean r-0.5107, P < 0.001) with those with a higher HbA1 having a
      faster rate of progression. In stepwise multivariate analysis both mean HbA1 mean
      diastolic blood pressure (P < 0.0001 and P = 0.019, respectively) was
      significantly and independently related with a faster rate of decline of GFR.
      CONCLUSIONS: Worse glycaemic control is associated with a faster rate of
      progression of diabetic nephropathy once blood pressure is controlled. Thus
      improvement of glycaemic control in patients where good blood pressure control
      has been achieved may potentially further delay the progression of nephropathy.

PMID- 9269706
TI  - The long-term tolerability of enalapril in hypertensive patients with renal
      impairment.
AB  - There has been some concern raised regarding the safe use of ACE-inhibitors in
      patients with severe renal insufficiency, including the development of
      hyperkalaemia in these patients. Therefore, the objective of the current analysis
      was to evaluate the long-term safety of enalapril in patients with severe renal
      sufficiency and hypertension. Three protocols with similar randomized, double
      blind, placebo-controlled designs were selected for analysis. A total of 153
      patients, enrolled at six sites, were treated for up to 3 years with enalapril;
      164 patients served as controls. One protocol used a fixed dose (5 mg/day) of
      enalapril, while the other two protocols allowed open titration up to 40 mg/day.
      The primary comparison was between the enalapril and control populations. For the
      analysis, patients, by treatment, were grouped according to the degree of renal
      insufficiency (serum creatinine > or < 3 mg/dl) at baseline. The incidence of the
      most common, as well as important, clinical and laboratory adverse events for
      this patient population were summarized. In addition, trends in important
      laboratory adverse events and the incidence of first-dose events, cough and
      angioedema were evaluated. The incidence of clinical adverse events was similar
      for both treatment groups, regardless of the severity of renal insufficiency.
      Seven patients died, four in the control group and three in the enalapril
      treatment group; none was considered related to treatment. Enalapril appeared to
      be well-tolerated in this group of patients with severe renal impairment.

PMID- 9269707
TI  - Parameters associated with chronic renal transplant failure.
AB  - BACKGROUND: Although chronic progressive renal transplant failure (CPTF) is one
      of the leading causes of end-stage renal disease its exact pathogenesis is still
      incompletely understood. Histopathological as well as clinical similarities
      between chronic native kidney diseases and CPTF open the possibility that the
      latter condition is not exclusively due to a prolonged immunological insult to
      the grafted organ but also is caused by a mismatch between the metabolic demands
      of the recipient and the excretory capacity of the transplanted kidney. In this
      retrospective study we defined clinical parameters which are associated with
      CPTF. METHODS: Creatinine clearance was followed in 469 patients 45 +/- 0.9
      months after transplantation for 2 years. Various immunological and non
      immunological parameters were included in an univariate and multivariate
      regression analysis to define those which are independently associated with CPTF,
      defined as a decrease of creatinine clearance during the study period. RESULTS:
      Of all the parameters proteinuria, systolic blood pressure, high Cyclosporin
      trough concentrations and the cumulative steroid dose were found to be
      significantly associated with CPTF. A persistent proteinuria of > 2 g/d during
      the observation period was found to have a positive predictive value of 83% for a
      deterioration of excretory kidney function of > or = 25% within 2 years.
      CONCLUSION: In CPTF immunological as well as non immunological factors are
      independently associated with the decline of excretory allograft function in the
      late postoperative period.

PMID- 9269708
TI  - Comparison between oogenesis and related ovarian structures in a reptile,
      Pseudemys scripta elegans (turtle) and in a bird Coturnix coturnix japonica
      (quail).
AB  - The aspect of the oogonia during their premitotic DNA synthesis and of the
      premeiocytes during their premeiotic DNA synthesis was studied in turtles by
      autoradiography, after injection of 3H-thymidine. As in the adult laying quail,
      the intrafollicular oocytes of the adult turtle go through three successive
      stages: prelampbrush, lampbrush and postlampbrush. During the prelampbrush and
      lampbrush stage two kinds of nucleoli exist: peripheral and central. In contrast
      to avian yolk, during its final rapid growth, no polyhedric protein yolk units
      were found in turtle yolk. As in the yellow yolk of quail, highly osmiophilic
      alcohol insoluble satellite yolk (egg oil) accumulates between the protein
      globular yolk of Pseudemys. Turtle yolk globules increase in volume by fusion.
      The penetration of peripherally assembled yolk in the turtle germinal disc is
      analogous to what we have described in the quail. Also in postlampbrush germinal
      discs subcortical ooplasmic organelles are present. Below the turtle germinal
      disc no structure comparable to the avian nucleus of Pander could be observed. No
      pyriform cells (as in squamate reptiles) and no pyriform-like cells (as in birds:
      Callebaut, 1991 b) were found in the chelonian ovarian granulosa layer. We could
      not demonstrate functional lacunoperitoneal communications via openings in the
      hilus ovarii of the turtle as is the case in birds.

PMID- 9269709
TI  - Prevention of the expression of incubation behaviour using passive immunisation
      against prolactin in turkey hens (Meleagris gallopavo).
AB  - The efficacy of injecting antibodies raised against turkey prolactin to prevent
      the expression of incubation behaviour has been investigated in turkey hens.
      Medium white turkey hens (n = 15 x 2) were injected three times weekly for 4
      consecutive weeks starting on week 5 of egg production. The hens were injected im
      with a volume of 1 mL per injection for the 1st week and 0.5 mL thereafter, of
      normal rabbit serum or serum containing antibodies raised against turkey
      prolactin (Guemene et al, 1994a). None of the 15 passively immunised hens
      expressed incubation behaviour, whereas, more than half (53%) of the control hens
      did express it. Plasma prolactin concentrations observed in the two groups
      presented comparable profiles until week 9 and from week 19 of egg production
      onward. Differences were, therefore, observed from week 10 until week 17 with the
      non immunised hens showing higher plasma prolactin concentrations than the
      immunised ones. This difference was related to the presence of incubating hens in
      the control group. A higher percentage of non immunised hens disrupted egg
      production during the course of the study and consequently immunised hens laid
      more eggs than the control ones. No change in plasma LH and oestradiol
      concentrations can be related to the immunisation procedure. We conclude that
      prevention of incubation behaviour can be achieved using passive immunisation
      against prolactin, prevention which resulted in more egg production under our
      experimental protocol.

PMID- 9269710
TI  - Fermentation of green alga sea-lettuce (Ulva sp) and metabolism of its sulphate
      by human colonic microbiota in a semi-continuous culture system.
AB  - The green alga, sea-lettuce (Ulva sp), could be considered as a new source of
      dietary fibre. Ulva, however, contains high levels of sulphate, part of which is
      chemically bound in soluble polymers (ulvan). The purpose of this study was to
      assess the fermentation characteristics and sulphate metabolism of Ulva and ulvan
      by human faecal bacteria fermentation system using a semi-continuous fermenter.
      Ulva and ulvan were poorly fermented, even after adaptation of the microbiota.
      Only 16.6% and 8.9% of Ulva and ulvan organic matter, respectively, were
      recovered as short chain fatty acids. Nevertheless, 40% of the sulphate in Ulva
      was dissimilated to sulphide by sulphate-reducing bacteria. Supplementation of
      Ulva with more fermentable polysaccharides, such as algal xylan and resistant
      starch, though decreasing the ammonia production originating from Ulva protein
      degradation, did not significantly reduce the sulphide levels. It is postulated
      that unless crude Ulva is desulphated, its daily consumption at a level of 20 g
      of dry product could stimulate colonic microbial sulphate reduction, which may
      have detrimental effects for the host.

PMID- 9269711
TI  - Spatial relationship between endophyll, primordial germ cells, sickle endoblast
      and upper layer in cultured avian blastoderms.
AB  - By isotopic quail-chicken chimera experiments of the Rauber's sickle or by
      radioactive labelling and isotopically replacing of the caudal endophyllic sheet
      in unincubated avian blastoderms, followed by culture, we demonstrated that the
      displacement of the endophyll by the cranially extending sickle endoblast is not
      exclusively a mechanical phenomenon, as suggested by earlier studies (Vakaet,
      1962 a, b). Indeed, our study suggests that the sickle endoblast also migrates
      centripetally very soon (already after 5 h) in and through the caudal endophyll
      before ingression of upper layer cells takes place. We also describe the early
      spatial relationship between the three elementary tissues (endophyll, Rauber's
      sickle, upper layer) (Callebaut et al, 1996a) and the induction phenomena between
      quail sickle endoblast and chicken upper layer (UL) during the formation of the
      primitive groove. The latter already develops before ingression occurs. We found
      no evidence for an endophyllic origin of avian primordial germ cells.

PMID- 9269712
TI  - In situ and in vitro ruminal starch degradation of untreated and formaldehyde
      treated wheat and maize.
AB  - Ruminal starch degradation of untreated and formaldehyde-treated wheat and maize
      was measured in situ (trial 1) and in vitro (trial 2). The in situ starch
      degradability was higher for wheat than for maize (82.1 vs 52.3%), for untreated
      cereals than for cereals treated with 1% formaldehyde (77.3 vs 67.0%) and for
      cereals treated with 1% formaldehyde than those treated with 5% formaldehyde
      (67.0 vs 57.2%). The in vitro results were similar. The treatment of cereals by
      formaldehyde decreased starch degradability more for wheat than for maize,
      suggesting that the treatment was more efficient when cereal starch and/or
      nitrogen was highly degradable. Formadehyde treatment of wheat was more effective
      at decreasing the rate of wheat protein degradability than starch degradability.
      The difference of response to treatment between the two cereals may be due to
      differences in properties of the protein matrix of these two cereals.

PMID- 9269713
TI  - Growth of a leguminous tree (Centrolobium tomentosum Guill. ex Benth.) inoculated
      with Rhizobium and mycorrhizal fungi.
AB  - Leguminous trees are being suggested for revegetation programs due to their
      ability to develop associations with rhizobia and mycorrhizal fungi. The growth
      of a native species of the Tropical Atlantic Forest, Centrolobium tomentosum, was
      evaluated in a native forest soil and in a Eucalyptus forest soil under different
      treatments of inoculation. C. tomentosum produced more biomass under nursery
      conditions after inoculation with Rhizobium BHICB-Ab1 associated with arbuscular
      mycorrhizal (AM). This treatment improved shoot and root growth and nodule weight
      under forest soil condition, while in eucalyptus soil only shoot biomass and
      nodule weight were significantly modified. In another experiment, using forest
      soil, height and stem diameter were also increased by dual inoculation
      procedures. The height and diameter growth promoting effect was observed when
      BHICB-Ab1 was used as inoculant associated with AM, but not with BHICB-Ab1 alone.
      In contrast, plants inoculated with BHICB-Ab3 alone were similar in height and
      diameter growth, to those which were inoculated with BHICB-Ab3 associated with
      AM. These results suggest that benefits of dual inoculation depend on triparty
      symbiosis and especially on the choice of Rhizobium strain.

PMID- 9269714
TI  - Advances in the use of monoclonal antibodies for blood group testing.
AB  - Until the '80s blood group reagents were composed of human or animal polyclonal
      antibodies; nowadays they are mainly produced from monoclonal antibodies. In this
      paper two aspects will be considered; firstly the evolution in the use of
      monoclonal reagents in France and secondly the quality of these new reagents in
      comparison with polyclonal reagents. From 1981 to 1995, 17567 batches of blood
      group reagents were analyzed and controlled by the French Blood Group Reference
      Laboratory (CNRGS). All data are given in six tables.

PMID- 9269715
TI  - Monoclonal anti-D for prophylaxis of RhD haemolytic disease of the newborn.
AB  - The incidence of Rh D haemolytic disease of the fetus and newborn has been
      dramatically reduced by the prophylactic administration of anti-D immunoglobulin
      to Rh D-negative women. This preventive treatment depends on adequate supplies of
      anti-D derived from plasma of immunised donors, and replacement with monoclonal
      anti-D would be advantageous. Two monoclonal antibodies, BRAD-3 (IgG3) and BRAD-5
      (IgG1) have been produced from EBV-transformed B-lymphoblastoid cell lines in
      Bristol and extensively characterised. Both have shown good (but differing)
      functional activities, determined by study of interactions of anti-D coated red
      cells with effector cells bearing IgG Fc receptors. Phase I clinical trials using
      Rh D negative male volunteers were undertaken in Bristol. The plasma half lives
      of BRAD-3 and BRAD-5 were characteristic for their IgG subclass, and both anti-D
      mediated accelerated circulatory clearance of D-positive red cells infused two
      days after i.m. injection of the antibodies. BRAD-3 and BRAD-5 were then shown to
      protect the volunteers from mounting a primary anti-D response to these D
      positive red cells, and thus they may be suitable for Rh D prophylaxis of Rh D
      negative women.

PMID- 9269716
TI  - Molecular genetics of glycophorin MNS variants.
AB  - The antigens for the MNS blood group system are Glycophorins A and B (GPA,GPB),
      products of the GPA gene family. The existence of close to 40 variant phenotypes
      of this blood group system has been documented by serological analyses. Here is
      summarized the molecular basis for a large number of variants, including all the
      variants of the Miltenberger complex and several isoforms of Sta; also, Dantu,
      Sat, He, Mg, and deletion variants Ena, S-s-U- and Mk. The diversity is based
      predominantly on gene recombinations, namely unequal homologous recombinations
      and/or gene conversions, often coupled to pre-mRNA splicing. Most rearrangements
      occurred between GPA and GPB alleles, and were confined to hot-spots within the 4
      kb region coding for the extracellular domain. The homologous region in GPE, the
      third member of the gene family, was involved only rarely. Sites of the variant
      epitopes are mapped to new intra- and inter-exon junctions or to patches of
      previously silenced sequences that become expressed following recombination.

PMID- 9269718
TI  - Blood group polymorphisms: molecular approach and biological significance.
AB  - Genes for 20 of the 23 human blood group systems have now been cloned and the
      molecular bases of the important polymorphisms within most of these systems are
      known. Most blood group polymorphisms are due to missense mutations resulting in
      amino acid substitutions, but other types of mutation are involved in blood group
      polymorphism including gene deletion, single base deletion, and exchange of
      genetic material between homologous genes. All the polymorphisms of the Kell
      system, for example, result from missense mutations. Comparison of the position
      of these mutations within the KEL gene with clusters of antigens determined by an
      immunochemical technique, suggests that the Kell-system antigens are not linear
      and are probably discontinuous. The biological significance of the proteins and
      glycoproteins carrying many of the blood group antigens is known, or at least can
      be speculated upon. Identification of the nonsense mutations responsible for some
      null-phenotypes has shown that these macromolecules are not usually essential for
      a healthy life. Little is known, however, about the biological significance of
      the blood group polymorphisms. Many macromolecules carrying blood group activity
      are receptors for pathogenic micro-organisms and these pathogens may well have
      played an important part in the evolution of blood group polymorphism. The Duffy
      glycoprotein is a chemokine receptor, but also a receptor for the malarial
      parasite Plasmodium vivax A mutation within an erythroid-specific transcription
      factor binding site within the FY gene, common in people of African origin but
      rare in other ethnic groups, results in the absence of the glycoprotein from red
      cells and, therefore, resistance to P. vivax infection, but presence of the
      glycoprotein in other tissues, reducing any potential selective disadvantage.

PMID- 9269717
TI  - Advances in molecular genetics of alpha-2- and alpha-3/4-fucosyltransferases.
AB  - Fucosyltransferases are involved in the last steps of the biosynthesis of ABH and
      Lewis oligosaccharide antigens. Seven human genes (FUT1 to FUT7) and one
      pseudogene (Sec 1) have been cloned and localized on different chromosomes
      (9q34.3; 11q21; 19p13.3 and 19q13.3). Their locations and their high degree of
      primary sequence identity, suggest that they have appeared by successive
      duplications followed by translocation and divergent evolution. Their expression
      is tissue specific and they present a switch during human embryo-foetal
      development similar to that of hemoglobins. Polymorphic genes FUT1-FUT2 and FUT3
      FUT5-FUT6 are organized in two clusters and each gene is partially or totally
      inactivated by different types of point mutations (nonsense, missense and frame
      shift), complete gene deletion or a fusion gene. The products of the monomorphic
      genes FUT4 and FUT7 seem implicated in cell-cell interactions during embryo
      foetal development and in the leukocyte adhesion phenomena to endothelial cells
      in the adult. A phylogenetic tree of the 28 available nucleotide coding sequences
      of fucosyltransferases has allowed us to situate the duplication events with
      respect to the separation of species from the main evolutionary path (nematods,
      birds, mammals, primates and humans). Recently, using a computer approach a
      general structure of fucosyltransferases has been proposed, inspired from the
      crystalline structure of the beta-glucosyltransferase of bacteriophage T4. This
      folding contains two domains with an alternate succession alpha and beta chains.
      In this model the GDP-fucose binding site would be located between the two
      domains.

PMID- 9269719
TI  - Vipera berus and V. ammodytes (Serpentes:Viperidae) represent new host for
      Caryospora simplex (Apicomplexa:Eimeriidae) in Europe.
AB  - During a survey of the coccidian parasites of reptiles, caryosporan oocysts wee
      found in the faeces of wild and captive European viperid snakes Vipera berus (L.)
      and V. ammodytes (L.). Thirty two of 37 examined V. berus (86%) and 9 of 17
      examined V. ammodytes (53%) specimens were found to be passing caryosporan
      oocysts. Morphological characters of all caryosporan isolates were identical and
      fitted well with the description of Caryospora simplex Leger, 1904. Experimental
      inoculation of severe combined immunodeficient (SCID) mice with seven isolates of
      C. simplex from V. berus or V. ammodytes confirmed the heteroxenous life cycle
      pattern, for the first time for isolates of evidently European origin.
      Caryosporan developmental stages were observed in the connective tissues of the
      nose, cheeks, ear and scrotum in all inoculated SCID mice. V. berus and V.
      ammodytes represent new hosts for C. simplex. The present paper represents the
      first widely based report on coccidian parasites of the genus Caryospora Leger in
      European viperids. Our findings indicate a wide distribution of C. simplex
      throughout the range of distribution of snakes of the genus Vipera.

PMID- 9269720
TI  - Isolation and characterization of cytosolic malate dehydrogenase from Trichomonas
      vaginalis.
AB  - Malate dehydrogenase (EC 1.1.1.37.) (MDH) was purified to apparent homogeneity
      from the cytosolic fraction of the protozoan Trichomonas vaginalis Donne. The
      four step purification included ion-exchange chromatography (DEAE-Sephacel and Q
      Sepharose, elution with NaCl) and affinity chromatography (Reactive Red Agarose,
      elution with NADH and NaCl). The enzyme was purified about 132-fold (30.6% yield)
      to a specific activity of 352 units mg-1. The Km values determined at pH 7.8 (pH
      optimum from 7.5 to 8.3) for oxaloacetate and NADH were 16.2 microM and 10.6
      microM, respectively. The MDH activity was inhibited by the substrate, decreasing
      to 50% at about 1 microM concentration of oxaloacetate. The reverse reaction from
      malate to oxaloacetate showed a pH optimum around pH 9.5. The Km for malate and
      NAD+ (determined at pH 7.8) were 1220 microM and 69.9 microM, respectively. SDS
      PAGE analysis of the purified MDH revealed a single band with an apparent size of
      34.5 kDa. The native molecular weight was estimated by HPLC gel filtration to be
      60 kDa, which indicates that the T. vaginalis MDH exists as a dimer.

PMID- 9269721
TI  - Electrophoretic variations of peptidase E (PEPE) in characterizing clones and
      isolates of Plasmodium falciparum from different geographical areas.
AB  - Six clones were obtained from each Plasmodium falciparum (Welch, 1897) isolate
      from different geographical areas, Gombak A (Malaysian), Gombak C (Malaysian), ST
      9 (Malaysian, ST 12 (Malaysian), ST 85 (Malaysian, ST 148 (Malaysian), Gambian
      (African) and TGR (Thailand) isolates using the limiting dilution method (Rosario
      1981). Forty-eight clones were obtained and were characterized by an
      electrophoresis isoenzyme analysis of PEPE (Peptidase E) (EC. 3.4.11 or 13).
      Results showed that they were pure clones as they were monovariant with regards
      to this enzyme unlike their parent isolates which were divariant.

PMID- 9269722
TI  - Role of grey squirrels and pheasants in the transmission of Borrelia burgdorferi
      sensu lato, the Lyme disease spirochaete, in the U.K.
AB  - In Britain, grey squirrels (Sciurus carolinensis Gmelin) and pheasants (Phasianus
      colchicus Linnaeus) are important hosts of larvae and nymphs of Ixodes ricinus
      L., the principal European vector of the Lyme disease spirochaete, Borrelia
      burgdorferi sensu lato. To test whether squirrels are competent hosts of B.
      burgdorferi s.l., three females were trapped in the wild and then held in
      captivity. Following treatment, each animal was exposed to uninfected
      xenodiagnostic I. ricinus ticks. Squirrel A (an adult) which was inoculated
      experimentally with B. burgdorferi s.l., transmitted the infection to
      xenodiagnostic ticks. In contrast, squirrel B (a juvenile that was not
      inoculated)-showed no evidence of infection. Xenodiagnostic ticks that fed on
      control squirrel C (an adult) became infected and subsequently transmitted the
      infection experimentally to an uninfected hamster. The results indicated that
      squirrel C had a disseminated infection acquired in the wild and which persisted
      for at least 11 weeks. These data clearly demonstrate that grey squirrels are
      amplifying and reservoir hosts of B. burgdorferi s.l. The strain associated with
      squirrels was related to the B. afzelii genotype. Two observations implicated
      pheasants in a similar role: (i) a high prevalence of infection in engorged
      larvae collected from trapped pheasants, and (ii) the detection of B. burgdorferi
      s.l. (B. garinii genotype) in the wattle of 1/10 pheasants using PCR.
      Xenodiagnostic experiments similar to those undertaken with the squirrels are
      needed to confirm the role of pheasants in the transmission cycle of Lyme disease
      spirochaetes.

PMID- 9269723
TI  - Goal-directed guidance of attention: evidence from conjunctive visual search.
AB  - Conjunctive visual search is most difficult when distractor types are in equal
      proportions and gets easier as the proportions diverge (e.g., E. Zohary & S.
      Hochstein, 1989). This may reflect restriction of search to the feature shared by
      the target and the less-frequent distractor. Alternatively, such effects could
      reflect target salience, which varies with distractor ratio. In 2 experiments, 60
      participants searched 64-element displays for a conjunctive target among
      distractors of 2 types in various proportions. Participants were correctly
      informed (Experiment 1) or misinformed (Experiment 2) about which distractor type
      would be less frequent on most trials. In both experiments, the distractor-ratio
      effect was significantly influenced by the information provided to participants.
      These findings demonstrate the efficacy of top-down information in guiding
      attention and show that it can be applied flexibly, weighted toward particular
      target features.

PMID- 9269724
TI  - Shape completion time depends on the size of the occluded region.
AB  - Observers made speeded discriminations of whole, occluded, and mosaic shapes.
      Shape matching times increased with the amount of occluded shape (Experiment 1),
      as did the time to merely discriminate 2 shapes (Experiments 2-4). By contrast,
      the time to judge the shape of the visible portion decreased with larger occluded
      regions (Experiments 5-7). Experiments 3 and 6 used motion parallax to show that
      different perceptual operations are involved in discriminating occluded versus
      mosaic shapes. Experiments 4 and 7 showed that shape completion was unaffected by
      spatial attention. Results suggest that shape completion is a rapid and
      obligatory aspect of perception. However, they also show that the time course of
      completion varies with the size of the hidden region.

PMID- 9269725
TI  - Repetition blindness for pseudoobject pictures.
AB  - In this study the nature of type activations that underlie repetition blindness
      (RB) was addressed. According to the token individuation hypothesis put forward
      to explain RB, both instances of a repeated stimulus make contact with the mental
      representation, or type, for that stimulus. In the resulting confusion only the
      first stimulus is encoded as an episodic instance or token. Type representations
      have traditionally been thought of as preexisting and are often linked within a
      network of nodes. The authors developed and tested a picture frequency task,
      which does not require stimulus naming, and used it to examine repetition
      performance for unfamiliar nonobject pictures. RB was found for these stimuli,
      despite the fact that they had no prior phonological or semantic representation.
      These results suggest that the reactivation of a newly formed visual type is
      sufficient to produce RB. Implications for the role of types in the token
      individuation hypothesis are discussed.

PMID- 9269726
TI  - Associative priming by targets and distractors during rapid serial visual
      presentation: does word meaning survive the attentional blink?
AB  - In 5 experiments, 432 college students viewed lists of words containing 2 targets
      (Target 1 [T1] and Target 2 [T2]) presented by rapid serial visual presentation
      at 10 words per second. Identification of T1 caused a 500-ms impairment in the
      identification of T2 (the attentional blink [AB]). Improved recall of T2 was
      observed throughout the time course of the AB when T2 was a strong associate of
      either T1 or a priming distractor (PD). When participants ignored T1, the AB was
      eliminated, but the amount of priming was not affected. Priming of T2 by PD was
      temporary (100-200 ms after the onset of PD). Although target priming and
      distractor priming both survived the AB, the 2 forms of priming appeared to have
      different bases. In contrast to priming by PD, priming by T1 was larger,
      modulated by backward associative strength, and longer lasting. Priming and the
      AB are hypothesized to result from on-line attentional processes, but recall from
      RSVP lists is also influenced by off-line memory processes.

PMID- 9269727
TI  - Integration of binocular stereopsis and structure from motion in the
      discrimination of noisy surfaces.
AB  - Integration of stereo and motion information was measured on the basis of
      observers' ability to discriminate between triangle- and sine-wave corrugated
      surfaces or sinusoidal surfaces of different spatial frequency. Discrimination
      performance for the triangle-sine task was consistent with independent processing
      of motion and stereo, but the spatial frequency discrimination task led to
      performance superior to that predicted by an independent combination of motion
      and stereo signals, indicating that the integration of stereo and motion depends
      on the type of 3-dimensional structure observers are required to discriminate.
      This pattern of results is consistent with the existence of multiple stereoscopic
      mechanisms suggested by psychophysical and neurophysiological data.

PMID- 9269728
TI  - Constraints common to apparent motion in visual, tactile, and auditory space.
AB  - A point-like stimulus was presented in a clockwise or counterclockwise sequence
      at 3, 4, 6, or 12 uniformly spaced locations around a circle in visual, tactile,
      or auditory space. In 4 experiments, the stimulators were (a) light-emitting
      diodes in the frontal plane, (b) mechanical stimulators on the palm, (c) airpuff
      nozzles around the head, and (d) loudspeakers around the head. For each spatial
      separation and stimulus-onset asynchrony (SOA) between successive stimuli around
      the circle, participants reported the direction of motion. Within each modality,
      the SOA required for 75% accurate discrimination of direction increased with the
      spatial separations. A time-distance constraint akin to Korte's third law of
      visual apparent motion can thus be obtained from responses that are objectively
      classifiable as correct or incorrect (without relying on subjective reports of
      "goodness" of apparent motion). Moreover, this time-distance constraint evidently
      generalizes across sensory modalities.

PMID- 9269729
TI  - Just-noticeable difference in the speed of cyclopean motion in depth and the
      speed of cyclopean motion within a frontoparallel plane.
AB  - Weber fractions for discriminating the speed and displacement of a cyclopean
      target moving in depth ranged, respectively, from .07-.17 and .06-.13 over 6
      observers. Corresponding data for a noncyclopean target were .07-.20 and .06-.12.
      For motion parallel to the frontal plane, corresponding data were .09-.20 .06
      .16, and .05-.13. All Weber fractions were independent of the direction of motion
      and of near versus far disparity. All observers based their judgments entirely on
      the task-relevant variable and ignored task-irrelevant variables in all cases. We
      conclude that speed and displacement are encoded independently and in parallel
      for motion in depth and for motion within a frontoparallel plane.

PMID- 9269731
TI  - From graphemes to abstract letter shapes: levels of representation in written
      spelling.
AB  - The letter substitution errors of 2 dysgraphic subjects who, despite relatively
      intact oral spelling, made well-formed letter substitution errors in written
      spelling, were studied. Many of these errors bear a general physical similarity
      to the intended target. Analyses revealed that this similarity apparently was
      based on the features of the component strokes of letters rather than on
      visuospatial characteristics. A comparison of these subjects' letter substitution
      errors with those of 2 other individuals with brain damage, whose damage was at a
      different level of processing, revealed that the latter subjects' errors are not
      explicable in terms of stroke-feature similarity. Strong support was found for
      the computation of multiple representational types in the course of written
      spelling. This system includes a relatively abstract, effector-independent
      representational level that specifies the features of the component strokes of
      letters.

PMID- 9269730
TI  - Misperceptions of angular velocities influence the perception of rigidity in the
      kinetic depth effect.
AB  - Accuracy in discriminating rigid from nonrigid motion was investigated for
      orthographic projections of three-dimension rotating objects. In 3 experiments
      the hypothesis that magnitudes of angular velocity are misperceived in the
      kinetic depth effect was tested, and in 4 other experiments the hypothesis that
      misperceiving angular velocities leads to misperceiving rigidity was tested. The
      principal findings were (a) the magnitude of perceived angular velocity is
      derived heuristically as a function of a property of the first-order optic flow
      called deformation and (b) perceptual performance in discriminating rigid from
      nonrigid motion is accurate in cases when the variability of the deformations of
      the individual triplets of points of the stimulus displays favors this
      interpretation and not accurate in other cases.

PMID- 9269732
TI  - The recognition potential, word difficulty, and individual reading ability: on
      using event-related potentials to study perception.
AB  - Ten observers detected words in a stream of random letters. The latency of the
      recognition potential (RP) was less for easier words. This implicated short
      latency processes in word detection. Reaction time (RT) and P3 latency decreases
      with training were attributed to improved motor preparation. The RT decrease with
      training was correlated with P3 (r = .67), but not RP (r = .04), latency
      reduction. P3 latency did not predict individual RT (r = .20), but RP latency did
      (r = .66). Twenty other subjects took the Verbal portion of a Graduate Record
      Examination to test whether the RP might be a better predictor of individual
      differences than P3. RP latency predicted a person's reading score (r = -.74),
      but P3 latency did not (r = .08). The word-difficulty effect and the shorter RP
      latency observed for superior readers supported the idea that the RP reflects
      perception that is based on language skill.

PMID- 9269733
TI  - Infants' recognition of contour-deleted figures.
AB  - Infants' recognition of contour-deleted figures was investigated in four
      experiments using a habituation procedure. The results indicate that 12-month-old
      infants could recognize line drawings of figures that were missing 33%, 50%, or
      even as much as 66% of their contour. This was so whether the contour-deleted
      versions were used on habituation or on test: Intact figures were recognized
      after habituation to contour-deleted exemplars, and in most cases contour-deleted
      ones were recognized after habituation to the intact figure. The single failure
      appeared to be due to difficulty in discriminating between two extremely
      impoverished test stimuli. Findings from the final experiment, in which infants
      recognized complements of contour-deleted stimuli but not scrambled versions,
      suggested that they fill in the gaps of the contour-deleted figures so as to
      create a figural whole.

PMID- 9269734
TI  - Frequency and consistency effects in a pure surface dyslexic patient.
AB  - Data are presented from a neurological patient (M.P.) with an acquired deficit
      for naming words with atypical spelling-sound correspondences. In Experiment 1,
      the degree of consistency within neighborhoods of orthographically similar words
      had a parallel impact on M.P.'s pronunciations of regular and irregular words and
      nonwords. This result is more compatible with models in which the same basic
      procedure, sensitive in a graded fashion to both frequency and consistency,
      computes pronunciations for all types of letter strings than it is with models
      postulating separate lexical and nonlexical mechanisms. In Experiment 2, both
      correct and regularized pronunciations of exception words yielded response times
      significantly modulated by word frequency, a finding not predicted by an current
      model. Neuropsychological observations provide an important additional source of
      evidence regarding models of cognitive function.

PMID- 9269735
TI  - Perceiving and tracking kinesthetic stimuli: further evidence of motor-perceptual
      interactions.
AB  - Two experiments pursued previous studies (P. Viviani & P. Mounoud, 1990; P.
      Viviani & N. Stucchi, 1989) on motor-perceptual interactions. The right arm of
      blindfolded participants was moved passively along elliptic trajectories.
      Kinematics was either coherent or at variance with the relation (two-thirds power
      law) observed in active movements. In Experiment 1 participants compared the
      horizontal and vertical extent of the ellipses. Kinematics affected aspect ratio
      discrimination: The direction along which the movement decelerated was
      subjectively stretched. In Experiment 2 participants used the left arm to
      reproduce in real time the movement of the right arm. The trajectories of the
      left arm presented a stretch similar to the perceptual illusion demonstrated in
      Experiment 1. Between-arm asynchrony suggests that the motor control system
      cannot use kinesthetic information that is at variance with the flow of
      reafferences normally associated with voluntary movements. It is argued that
      these interactions occur at the level of a central amodal representation of the
      stimuli.

PMID- 9269736
TI  - Optimal control of the chemotherapy of HIV.
AB  - Using an existing ordinary differential equation model which describes the
      interaction of the immune system with the human immunodeficiency virus (HIV), we
      introduce chemotherapy in an early treatment setting through a dynamic treatment
      and then solve for an optimal chemotherapy strategy. The control represents the
      percentage of effect the chemotherapy has on the viral production. Using an
      objective function based on a combination of maximizing benefits based on T cell
      counts and minimizing the systemic cost of chemotherapy (based on high drug
      dose/strength), we solve for the optimal control in the optimality system
      composed of four ordinary differential equations and four adjoint ordinary
      differential equations.

PMID- 9269737
TI  - Stochastic epidemics: the probability of extinction of an infectious disease at
      the end of a major outbreak.
AB  - The aim of this study is to derive an asymptotic expression for the probability
      that an infectious disease will disappear from a population at the end of a major
      outbreak ('fade-out'). The study deals with a stochastic SIR-model. Local
      asymptotic expansions are constructed for the deterministic trajectories of the
      corresponding deterministic system, in particular for the deterministic
      trajectory starting in the saddle point. The analytical expression for the
      probability of extinction is derived by asymptotically solving a boundary value
      problem based on the Fokker-Planck equation for the stochastic system. The
      asymptotic results are compared with results obtained by random walk simulations.

PMID- 9269738
TI  - The dynamics of cocirculating influenza strains conferring partial cross
      immunity.
AB  - We develop a model that describes the dynamics of a finite number of strains that
      confer partial cross-protection among strains. The immunity structure of the host
      population is captured by an index-set notation where the index specifies the set
      of strains to which the host has been exposed. This notation allows us to derive
      threshold conditions for the invasion of a new strain and to show the existence
      of an endemic multi-strain equilibrium in a special case. The dynamics of systems
      consisting of more than two strains can exhibit sustained oscillations caused by
      an overshoot in the immunity to a specific strain of cross-protection is
      sufficiently strong.

PMID- 9269739
TI  - Rheumatoid Arthritis--heresies and speculations.

PMID- 9269740
TI  - On the dialectic between molecular biology and integrative physiology: toward a
      new medical science.

PMID- 9269741
TI  - Long-term control of blood pressure and sodium balance: is the baseline
      nocturnal?

PMID- 9269742
TI  - Thyroxine's evolutionary roots.

PMID- 9269743
TI  - Humbug breast cancer follies: odds ratios for the relative risk of truth:
      unsolicited reportage from a board certified non-epidemiologist.

PMID- 9269744
TI  - Fractal variability versus pathologic periodicity: complexity loss and stereotypy
      in disease.

PMID- 9269745
TI  - The Lactobacillus anomaly: total iron abstinence.

PMID- 9269746
TI  - Ethical conflicts in regulating the start of life.

PMID- 9269747
TI  - Proof.

PMID- 9269748
TI  - Bupropion (Zyban) for smoking cessation.

PMID- 9269749
TI  - Topical drugs for aging skin.

PMID- 9269750
TI  - Ropivacaine--a new local anesthetic.

PMID- 9269751
TI  - Stem cell factor and hematopoiesis.

PMID- 9269752
TI  - Tat-human immunodeficiency virus-1 induces human monocyte chemotaxis by
      activation of vascular endothelial growth factor receptor-1.
AB  - Human immunodeficiency virus-1 (HIV-1) Tat protein can be released by infected
      cells and activates mesenchymal cells. Among these, monocytes respond to Tat by
      migrating into tissues and releasing inflammatory mediators. In the present
      study, we have examined the molecular mechanism of monocyte activation by Tat,
      showing that this viral protein signals inside the cells through the tyrosine
      kinase receptor for vascular endothelial growth factor encoded by fms-like
      tyrosine kinase gene (VEGFR-1/Flt-1). Subnanomolar concentrations of Tat induced
      monocyte chemotaxis, which was inhibited by cell preincubation with vascular
      endothelial growth factor-A (VEGF-A). This desensitisation was specific for VEGF
      A, because it not was observed with FMLP. In addition, the soluble form of VEGFR
      1 specifically inhibited polarization and migration induced by Tat and VEGF-A,
      thus confirming the common use of this receptor. Binding studies performed at
      equilibrium by using radiolabeled Tat showed that monocytes expressed a unique
      class of binding site, with a kd of approximately 0.2 nmol/L. The binding of
      radiolabeled Tat to monocyte surface and the cross-linking to a protein of 150 kD
      was inhibited specifically by an excess of cold Tat or VEGF-A. Western blot
      analysis with an antibody anti-VEGFR-1/Flt-1 performed on monocyte
      phosphoproteins immunoprecipitated by an monoclonal antibody anti-phosphotyrosine
      showed that Tat induced a rapid phosphorylation in tyrosine residue of the 150-kD
      VEGFR-1/Flt-1. Taken together, these results suggest that biologic activities of
      HIV-1 Tat in human monocytes may, at least in part, be elicited by activation of
      VEGFR-1/Flt-1.

PMID- 9269753
TI  - Upregulation of the elongation factor-1alpha gene by p53 in association with
      death of an erythroleukemic cell line.
AB  - Genes upregulated by p53 were screened using an erythroleukemic cell line (1-2-3)
      that expresses only the temperature-sensitive p53 by the mRNA differential
      display method. One of the upregulated genes was identified as the elongation
      factor-1alpha (EF-1alpha) gene, an essential component of the eukaryotic
      translation apparatus. Three p53-responsive elements were found in the mouse EF
      1alpha gene and in the corresponding human, rat, and frog genes. These elements
      conferred the capacity for induction by p53. EF-1alpha is also a microtubule
      severing protein. Upon the temperature-shift, the cells developed the morphology
      and the localization of alpha-tubulin similar to those of the cells treated with
      vincristine, a drug that affects microtubules. The microtubule-severing
      associated with upregulation of EF-1alpha by p53 may be a cause of the cell
      death.

PMID- 9269754
TI  - Human immunodeficiency virus-1 entry into purified blood dendritic cells through
      CC and CXC chemokine coreceptors.
AB  - Blood dendritic cells (DC) are susceptible to both macrophage (M) and T-cell line
      (T) tropic human immunodeficiency virus type 1. The CC chemokines RANTES,
      macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, eotaxin, and, to
      a lesser extent, monocyte chemoattractant protein-1 (MCP-1) and MCP-4 blocked
      entry of M-tropic virus into blood DC. The CXC chemokine, SDF-1, a fusin (CXCR4
      chemokine receptor) ligand, and an antifusin antibody inhibited DC entry by T
      tropic virus. Purified blood DC contained CCR1, CCR2, CCR3, and CCR5 as well as
      the CXCR4 chemokine receptor RNA transcripts and high levels of fusin on the cell
      surface. The coexpression of multiple chemokine receptors offers a molecular
      mechanism to explain the permissiveness of DC for both M- and T-tropic viruses.

PMID- 9269755
TI  - Aberrations of the B-cell receptor B29 (CD79b) gene in chronic lymphocytic
      leukemia.
AB  - Leukemic B cells in chronic lymphocytic leukemia (B-CLL) typically exhibit low or
      undetectable surface Ig. Because the B29 (CD79b and Ig beta) and mb-1 (CD79a and
      Ig alpha) gene products are required for surface Ig display in the B-cell
      receptor complex (BCR), we analyzed the expression of these genes in B-CLL cells.
      The majority (83%) of the randomly selected B-CLL patient samples analyzed
      exhibited low or undetectable surface BCR measured by mu heavy chain and B29
      expression. Levels of mb-1 mRNA in these B-CLL samples with low surface BCR were
      similar to those in normal B cells. Among those with decreased surface
      expression, B29 mRNA was not detected in half of these B-CLL samples. The
      remaining B-CLL samples with diminished surface BCR contained normal levels of
      B29 mRNA. Further analysis of cDNA clones from the majority of these latter
      samples contained point mutations, insertions, or deletions that were largely
      located in the B29 transmembrane and cytoplasmic domains. These results indicate
      the occurrence of somatic mutations predicted to affect B29 expression and/or
      function in the majority of B-CLL and suggest that these aberrations underlie the
      diminished surface BCR display and loss of BCR signaling characteristic of this
      leukemia.

PMID- 9269757
TI  - Hypermethylation of the p15INK4B gene in myelodysplastic syndromes.
AB  - Previous studies have shown that the cyclin-dependent kinase inhibitor (CDKI)
      genes p15INK4B and p16INK4A are frequently inactivated by genetic alterations in
      many malignant tumors and that they are candidate tumor-suppressor genes.
      Although genetic alterations in these genes may be limited to lymphoid
      malignancies, it has been reported that their inactivation by aberrant
      methylation of 5' CpG islands may be involved in various hematologic
      malignancies. In this study, we investigated the p15INK4B and p16INK4A genes to
      clarify their roles in the pathogenesis of myelodysplastic syndrome (MDS).
      Southern blotting analysis showed no gross genetic alterations in either of these
      genes. However, hypermethylation of the 5' CpG island of the p15INK4B gene
      occurred frequently in patients with MDS (16/32 [50%]). Interestingly, the
      p15INK4B gene was frequently methylated in patients with high-risk MDS
      (refractory anemia with excess blasts [RAEB], RAEB in transformation [RAEB-t],
      and overt leukemia evolved from MDS; 14/18 [78%]) compared with patients with low
      risk MDS (refractory anemia [RA] and refractory anemia with ring sideroblast
      [RARS]; 1/12 [8%]). Furthermore, methylation status of the p15INK4B gene was
      progressed with the development of MDS in most patients examined. In contrast,
      none of the MDS patients showed apparent hypermethylation of the p16INK4A gene.
      These results suggest that hypermethylation of the p15INK4B gene is involved in
      the pathogenesis of MDS and is one of the important late events during the
      development of MDS.

PMID- 9269756
TI  - Improved sensitivity of BCR-ABL detection: a triple-probe three-color
      fluorescence in situ hybridization system.
AB  - Chronic myeloid leukemia is a clonal stem cell disorder associated with the
      Philadelphia (Ph) translocation [t(9;22) (q34;q11)]. As a result of the Ph
      translocation, parts of the ABL and BCR genes become fused. Cytogenetic
      quantification of Ph+ metaphases can be used to monitor patient response to
      treatment but is of limited sensitivity and applies only to cycling cells.
      Fluorescence in situ hybridization (FISH) with probes from the BCR and ABL
      regions can also identify the Ph translocation in interphase cells. Established
      systems for the detection of fusion genes by FISH rely on colocalization of two
      different probes but are associated with a high rate of false-positive results.
      We have introduced a third probe labeled with a different fluorochrome to create
      a triple-probe/three-color system that permits identification of both the Ph
      chromosome and the derivative 9 chromosome in Ph+ cells. This system was used to
      determine the frequency of interphase cells carrying the BCR-ABL fusion gene in
      bone marrow and peripheral blood granulocytes from patients showing variable
      cytogenetic responses to interferon. Our data show that the triple-probe/three
      color approach allows highly sensitive detection of residual disease. Moreover,
      this method is readily applicable to the analysis of other chromosome
      translocations.

PMID- 9269758
TI  - Marrow transplants from unrelated donors for treatment of Philadelphia chromosome
      positive acute lymphoblastic leukemia.
AB  - Transplantation of marrow from unrelated donors was investigated in patients with
      Philadelphia chromosome-positive (Ph1+) acute lymphoblastic leukemia (ALL) who
      lacked a suitable family donor. Eighteen patients underwent transplantation at
      our center between 1988 and 1995. The median patient age was 25 years (range, 1.7
      to 51 years). Seven patients were in first complete remission, 1 in second
      remission, 3 in first relapse, and the remaining 7 had more advanced or
      chemotherapy refractory leukemia at transplant. All patients were conditioned
      with cyclophosphamide and total body irradiation followed by marrow transplants
      from closely HLA-matched, unrelated volunteers. Posttransplant graft-versus-host
      disease (GVHD) prophylaxis included methotrexate with either cyclosporine or
      FK506. Graft failure was not observed. Severe (grades III-IV) GVHD appeared in 6
      of 17 evaluable patients and chronic extensive GVHD in 7 of 13 patients at risk.
      Five patients had recurrent ALL after transplantation and another 4 died from
      causes other than leukemia. Six patients transplanted in first remission, 2 in
      first relapse, and 1 in second remission remain alive and leukemia-free at a
      median follow-up of 17 months (range, 9 to 73 months). The probability of
      leukemia-free survival at 2 years is 49% +/- 12%. These data indicate that
      unrelated donor marrow transplantation is an effective treatment option for
      patients with early stage Ph1+ ALL without a family match and suggest that in
      such patients an unrelated donor search should be initiated as soon as possible
      after diagnosis.

PMID- 9269759
TI  - Modulation of cytokine release and neutrophil function by granulocyte colony
      stimulating factor during endotoxemia in humans.
AB  - In this double-blind, cross-over, placebo-controlled, randomized study, two
      groups of eight healthy male volunteers were challenged with endotoxin (4 ng/kg)
      on two occasions, once in conjunction with placebo and once with granulocyte
      colony-stimulating factor (G-CSF; 5 microg/kg). In group 1, G-CSF was
      administered intravenously 2 hours before endotoxin challenge; in group 2, G-CSF
      was administered subcutaneously 24 hours before endotoxin challenge. In group 1,
      G-CSF significantly enhanced the release of tumor necrosis factor (TNF),
      interleukin-6 (IL-6), IL-8, IL-1 receptor antagonist (IL-1ra), and soluble TNF
      receptors. In group 2, G-CSF significantly reduced IL-8 concentrations and
      modestly attenuated TNF and IL-6 levels. In this group, IL-1ra and soluble TNF
      receptors were enhanced by G-CSF pretreatment and lipopolysaccharide (LPS)
      induced soluble TNF receptor release was further augmented, whereas LPS-induced
      IL-1ra concentrations remained unaltered. Both pretreatments with G-CSF increased
      LPS-induced peripheral neutrophilia; the expression of CD11b, CD18, and CD67; and
      the release of elastase and lactoferrin. Both pretreatments also down-regulated
      neutrophil L-selectin expression and prevented the endotoxin-induced pulmonary
      neutrophil accumulation during the first 2 hours after endotoxin challenge. These
      data indicate that two different pretreatments with G-CSF result in differential
      effects on LPS-induced cytokine release but similar effects on LPS-induced
      neutrophil activation and changes in expression of cell surface molecules.
      Finally, regardless of the effects of G-CSF on LPS-induced cytokine release, G
      CSF blocks LPS-induced pulmonary granulocyte accumulation.

PMID- 9269760
TI  - flt3 ligand in cooperation with transforming growth factor-beta1 potentiates in
      vitro development of Langerhans-type dendritic cells and allows single-cell
      dendritic cell cluster formation under serum-free conditions.
AB  - Using a recently described serum-free culture system of purified human CD34+
      progenitor cells, we show here a critical cooperation of flt3 ligand (FL) with
      transforming growth factor-beta1 (TGF-beta1) in the induction of in vitro
      dendritic cell/Langerhans cell (DC/LC) development. The addition of FL to serum
      free cultures of CD34+ cells supplemented with TGF-beta1, granulocyte-macrophage
      colony-stimulating factor, tumor necrosis factor alpha, and stem cell factor
      strongly increases both percentages (mean, 36% +/- 5% v 64% +/- 4%; P = .001) and
      total numbers (4.4- +/- 0.8-fold) of CD1a+ dendritic cells. These in vitro
      generated CD1a+ cells molecularly closely resemble a particular type of DC known
      as an epidermal Langerhans cell. Generation of DC under serum-free conditions was
      found to strictly require supplementation of culture medium with TGF-beta1. Upon
      omission of TGF-beta1, percentages of CD1a+ DC decreased (to mean, 10% +/- 8%; P
      = .001) and, in turn, percentages of granulomonocytic cells (CD1a- cells that are
      lysozyme [LZ+]; myeloperoxidase [MPO+]; CD14+) increased approximately threefold
      (P < .05). Furthermore, in the absence of TGF-beta1, FL consistently promotes
      generation of LZ+, MPO+, and CD14+ cells, but not of CD1a+ cells. Serum-free
      single-cell cultures set up under identical TGF-beta1- and FL-supplemented
      culture conditions showed that high percentages of CD34+ cells (mean, 18% +/- 2%;
      n = 4) give rise to day-10 DC colony formation. The majority of cells in these DC
      containing colonies expressed the Langerhans cell/Birbeck granule specific marker
      molecule Lag. Without TGF-beta1 supplementation, Lag+ colony formation is minimal
      and formation of monocyte/macrophage-containing colonies predominates. Total
      cloning efficiency in the absence and presence of TGF-beta1 is virtually
      identical (mean, 41% +/- 6% v 41% +/- 4%). Thus, FL has the potential to strongly
      stimulate DC/LC generation, but has a strict requirement for TGF-beta1 to show
      this costimulatory effect.

PMID- 9269761
TI  - Hematopoietic-specific genes are not induced during in vitro differentiation of
      scl-null embryonic stem cells.
AB  - The helix-loop-helix transcription factor, scl, plays an essential role in
      hematopoietic development. Embryos in which the gene has been disrupted fail to
      develop yolk sac erythropoiesis, and scl-null embryonic stem cells do not
      contribute to hematopoiesis in chimeric mice. To analyze the molecular
      consequences of scl deficiency, we compared the gene expression profiles of
      control (wild-type and scl-heterozygous) and scl-null embryonic stem cells
      differentiated in vitro for up to 12 days. In control and scl-null embryoid
      bodies the temporal expression pattern of genes associated with the formation of
      ventral mesoderm, such as Brachyury, bone morphogenetic protein-4, and flk-1, was
      identical. Similarly, GATA-2, CD34, and c-kit, which are coexpressed in
      endothelial and hematopoietic lineages, were expressed normally in scl-null
      embryonic stem cell lines. However, hematopoietic-restricted genes, including the
      transcription factors GATA-1, EKLF, and PU.1 as well as globin genes and
      myeloperoxidase, were only expressed in wild-type and scl-heterozygous embryonic
      stem cells. Indirect immunofluorescence was used to confirm the observations that
      GATA-1 and globins were only present in control embryoid bodies but that CD34 was
      found on both control and scl-null embryoid bodies. These data extend the
      previous gene ablation studies and support a model whereby scl is absolutely
      required for commitment of a putative hemangioblast to the hematopoietic lineage
      but that it is dispensable for endothelial differentiation.

PMID- 9269762
TI  - Anandamide, a natural ligand for the peripheral cannabinoid receptor is a novel
      synergistic growth factor for hematopoietic cells.
AB  - We recently demonstrated that the gene encoding the peripheral cannabinoid
      receptor (Cb2) may be a proto-oncogene involved in murine myeloid leukemias. We
      show here that Cb2 may have a role in hematopoietic development. RNAse protection
      analysis showed that Cb2 is normally expressed in spleen and thymus. Cb2 mRNA is
      also expressed in 45 of 51 cell lines of distinct hematopoietic lineages, ie,
      myeloid, macrophage, mast, B-lymphoid, T-lymphoid, and erythroid cells. The
      effect of the fatty acid anandamide, an endogenous ligand for cannabinoid
      receptors, on primary murine marrow cells and hematopoietic growth factor (HGF)
      dependent cell lines was then investigated. In vitro colony cultures of normal
      mouse bone marrow cells showed anandamide to potentiate interleukin-3 (IL-3)
      induced colony growth markedly. Whereas HGFs alone stimulate proliferation of the
      various cell lines in serum-free culture only weakly, anandamide enhances the
      proliferative response of the cell lines to HGFs profoundly. This was apparent
      for responses induced by IL-3, granulocyte-macrophage colony-stimulating factor,
      granulocyte colony-stimulating factor, and erythropoietin. Anandamide was already
      effective at concentrations as low as 0.1 to 0.3 micromol/L and plateau effects
      were reached at 0.3 to 3 micromol/L. The addition of anandamide as single growth
      factor had no effect. The costimulatory effect of anandamide was not evident when
      cells were cultured with fetal calf serum (FCS), suggesting that FCS contains
      anandamide or another ligand capable of activating the peripheral cannabinoid
      receptor. Other cannabinoid ligands did not enhance the proliferative
      responsiveness of hematopoietic cells to HGFs. Transfection experiments of Cb2 in
      myeloid 32D cells showed that anandamide specifically activates proliferation
      through activation of the peripheral cannabinoid receptor. Anandamide appears to
      be a novel and synergistic growth stimulator for hematopoietic cells.

PMID- 9269763
TI  - CD34+ hematopoietic progenitors from human cord blood differentiate along two
      independent dendritic cell pathways in response to granulocyte-macrophage colony
      stimulating factor plus tumor necrosis factor alpha: II. Functional analysis.
AB  - In response to granulocyte-macrophage colony-stimulating factor plus tumor
      necrosis factor alpha, cord blood CD34+ hematopoietic progenitor cells
      differentiate along two unrelated dendritic cell (DC) pathways: (1) the
      Langerhans cells (LCs), which are characterized by the expression of CD1a,
      Birbeck granules, the Lag antigen, and E cadherin; and (2) CD14+ cell-derived
      DCs, characterized by the expression of CD1a, CD9, CD68, CD2, and factor XIIIa
      (Caux et al, J Exp Med 184:695, 1996). The present study investigates the
      functions of each population. Although the two populations are equally potent in
      stimulating naive CD45RA cord blood T cells through apparently identical
      mechanisms, each also displays specific activities. In particular CD14-derived
      DCs show a potent and long-lasting (from day 8 to day 13) antigen uptake activity
      (fluorescein isothiocyanate dextran or peroxidase) that is about 10-fold higher
      than that of CD1a+ cells, which is restricted to the immature stage (day 6). The
      antigen capture is exclusively mediated by receptors for mannose polymers. The
      high efficiency of antigen capture of CD14-derived cells is coregulated with the
      expression of nonspecific esterase activity, a tracer of lysosomial compartment.
      In contrast, the CD1a+ population never expresses nonspecific esterase activity.
      The most striking difference is the unique capacity of CD14-derived DCs to induce
      naive B cells to differentiate into IgM-secreting cells, in response to CD40
      triggering and interleukin-2. Thus, although the two populations can allow T-cell
      priming, initiation of humoral responses might be preferentially regulated by the
      CD14-derived DCs. Altogether, those results show that different pathways of DC
      development might exist in vivo: (1) the LC type, which might be mainly involved
      in cellular immune responses, and (2) the CD14-derived DC related to dermal DCs
      or circulating blood DCs, which could be involved in humoral immune responses.

PMID- 9269764
TI  - Expression of activated mutants of the human interleukin-3/interleukin
      5/granulocyte-macrophage colony-stimulating factor receptor common beta subunit
      in primary hematopoietic cells induces factor-independent proliferation and
      differentiation.
AB  - To date, several activating mutations have been discovered in the common signal
      transducing subunit (h(beta)c) of the receptors for human granulocyte-macrophage
      colony-stimulating factor, interleukin-3, and interleukin-5. Two of these,
      FIdelta and I374N, result in a 37 amino acid duplication and a single amino acid
      substitution in the extracellular domain of h(beta)c, respectively. A third,
      V449E, results in a single amino acid substitution in the transmembrane domain.
      Previous studies comparing the activity of these mutants in different
      hematopoietic cell lines imply that the transmembrane and extracellular mutations
      act by different mechanisms and suggest the requirement for cell type-specific
      molecules in signalling. To characterize the ability of these mutant h(beta)c
      subunits to mediate growth and differentiation of primary cells and hence
      investigate their oncogenic potential, we have expressed all three mutants in
      primary murine hematopoietic cells using retroviral transduction. It is shown
      that, whereas expression of either extracellular h(beta)c mutant confers factor
      independent proliferation and differentiation on cells of the neutrophil and
      monocyte lineages only, expression of the transmembrane mutant does so on these
      lineages as well as the eosinophil, basophil, megakaryocyte, and erythroid
      lineages. Factor-independent myeloid precursors expressing the transmembrane
      mutant display extended proliferation in liquid culture and in some cases yielded
      immortalized cell lines.

PMID- 9269765
TI  - Novel interaction of apolipoprotein(a) with beta-2 glycoprotein I mediated by the
      kringle IV domain.
AB  - Lipoprotein(a) [Lp(a)], which has been shown to interact with fibrin(ogen) and
      other components of the blood clotting cascade, is a major independent risk
      factor for atherothrombotic disease in humans. The physiological function(s) of
      Lp(a), as well as the precise mechanism(s) by which high plasma levels of Lp(a)
      increase risk are unknown. Identification of further potential apo(a)-protein
      ligands may be crucial to illuminate apo(a)'s function(s) and pathophysiological
      properties. We used the repetitive apo(a) kringle IV type 2, which is variable in
      number in apo(a), to screen a human liver cDNA library by the yeast two-hybrid
      interaction trap system. Among 11 positive clones that emerged from the screen,
      eight clones were identified as beta-2 glycoprotein I and one as fibronectin.
      Coimmunoprecipitation experiments confirmed that beta-2 glycoprotein I and
      apo(a)/Lp(a) interact in human plasma and in cell culture supernatants of COS-1
      cells, which ectopically expressed apo(a). The apo(a)-beta2-glycoprotein I
      interaction indicates new potential roles for Lp(a) in fibrinolysis and
      autoimmunity.

PMID- 9269766
TI  - Regulated secretion in platelets: identification of elements of the platelet
      exocytosis machinery.
AB  - To further characterize the molecular mechanisms of platelet function, we have
      sought to identify some of the proteins that mediate the secretory events of the
      platelet release reaction. We report that platelets contain the general elements
      of the membrane transport apparatus: N-ethylmaleimide sensitive fusion protein
      (NSF), p115/transcytosis-associated protein (p115/TAP), and the soluble NSF
      attachment proteins (alpha- and, gamma-SNAP). The cDNAs encoding two of these
      proteins, alpha- and gamma-SNAP, have been cloned from a human platelet-derived
      cDNA library. Platelet membrane extracts possess SNAP receptor (SNARE) activity,
      suggesting that the class of proteins (SNAREs) proposed to provide the
      specificity for vesicle docking and membrane fusion are present in platelets. To
      identify these proteins, we have used specific antibodies against known SNAREs to
      probe platelet extracts. Syntaxin 2 and 4 can be readily detected in platelet
      membrane preparations and are shown to participate in 20 S complex formation.
      Syntaxin 1, 3, and 5 could not be detected. Other known SNARE and SNARE
      associated proteins such as vesicle-associated membrane protein
      (VAMP)/synaptobrevin 2, SNAP-25, synaptophysin, or synaptotagmin I could not be
      immunochemically detected in platelet membrane preparations. The presence of both
      the general transport proteins (NSF and SNAPs) and specific transport proteins
      (syntaxin 2 and 4) indicates that platelet exocytosis uses a molecular mechanism
      similar to other secretory cells such as neurons. However, the subcellular
      concentrations of these proteins suggest that, unlike neuronal secretion, granule
      to plasma membrane docking may be the limiting step in platelet exocytosis.

PMID- 9269767
TI  - Interleukin-6 downregulates factor XII production by human hepatoma cell line
      (HepG2).
AB  - Involvement of the contact system of coagulation in the pathogenesis of various
      inflammatory diseases is suggested by reduced plasma levels of factor XII
      (Hageman factor) and prekallikrein generally considered to result from activation
      of the contact system. However, in many of these diseases patients develop an
      acute-phase response and, therefore, an alternative explanation for the decreased
      levels of factor XII could be the downregulation of factor XII gene expression in
      the liver as described for negative acute-phase proteins. We report here that
      interleukin-6 (IL-6), the principal cytokine mediating the synthesis of most
      acute-phase proteins in the liver, downregulates the production of factor XII by
      the human hepatoma cell line HepG2 by up to 75%. The decrease in protein
      secretion correlated with an equivalent decrease of factor XII mRNA likely
      indicating a pretranslational control of factor XII gene expression by IL-6.
      Downregulation of factor XII production by IL-6 in vitro parallelled that of
      transthyretin, a known negative acute-phase protein. Moreover, we show that, in
      patients developing an acute-phase response after immunotherapy with IL-2, plasma
      levels of factor XII correlate (r = .76, P < .0001) with those of transthyretin.
      Taken together, these results suggest that factor XII behaves as a negative acute
      phase protein.

PMID- 9269768
TI  - Human kininogens regulate thrombin binding to platelets through the glycoprotein
      Ib-IX-V complex.
AB  - We and others have shown that both high and low molecular mass kininogens are
      able to inhibit the thrombin-induced aggregation of gel-filtered platelets,
      indicating that the locus for inhibition resides in the heavy chain. The
      inhibitory site is present in domain 3, confined to the C-terminal portion of the
      region encoded by exon 7 (K270-G292), and the minimal effective sequence is a
      heptapeptide (L271-A277; Kunapuli et al, J Biol Chem 271:11228, 1996). Kininogens
      inhibit thrombin binding to platelets and thus inhibit thrombin-induced
      aggregation. The molecular mechanism by which kininogens inhibit thrombin-induced
      aggregation of platelets is unknown. Thrombin has previously been shown to bind
      to two receptors on the platelet surface, glycoprotein (GP) Ib-IX-V complex and
      the hepta-spanning transmembrane receptor coupled to G protein(s). We now show
      that, unlike its effect on normal platelets, kininogen (2 micromol/L) did not
      inhibit the thrombin-induced aggregation of Bernard-Soulier platelets, which lack
      the GP Ib-IX-V complex, suggesting that kininogen interacts either directly or
      indirectly with that complex and restricts access by thrombin to this receptor.
      We further show that both recombinant K270-G292 polypeptide and the synthetic
      peptide L271-A277 derived from high molecular mass kininogen lower thrombin
      binding to platelets in a manner similar to monoclonal antibodies to or ligands
      (von Willebrand factor and echicetin) of GP Ib-IX. The anti-GP Ib-IX-V complex
      antibodies, TM-60 and SZ 2, can inhibit 125I-high molecular mass kininogen
      binding to platelets. Conversely, kininogen could block the binding of
      biotinylated TM-60 or of 125I-SZ 2. Kininogen inhibited the binding of
      biotinylated thrombin bound to a mouse fibroblast cell line transfected with the
      GP Ib-IX-V complex. These results indicated that kininogen binds to the GP Ib-IX
      V complex modulating thrombin binding to platelets and the consequent platelet
      aggregation. Kininogen can thus serve as an important regulator of the early
      stages of platelet stimulation by thrombin.

PMID- 9269769
TI  - Platelet adhesion to collagen under flow causes dissociation of a phosphoprotein
      complex of heat-shock proteins and protein phosphatase 1.
AB  - Phosphorylation/dephosphorylation events in human blood platelets were
      investigated during their adhesion to collagen under flow conditions. Using 32P
      labeled platelets and one-dimensional gel electrophoresis, we found that adhesion
      to collagen mediated primarily by the alpha2beta1 integrin resulted in a strong
      dephosphorylation of several protein bands. Neither adhesion to polylysine nor
      thrombin-induced aggregation caused similar protein dephosphorylation. In
      addition, treatment with okadaic acid (OA), an inhibitor of serine/threonine
      protein phosphatases type 1 (PP1) and 2A (PP2A), caused significant inhibition of
      adhesion, suggesting that adhesion is regulated by OA-sensitive phosphatases.
      Recent studies indicate that phosphatases may be associated with the heat-shock
      proteins. Immunoprecipitations with antibodies against either the heat-shock
      cognate protein 70 (hsc70) or heat-shock protein 90 (hsp90) showed the presence
      of a phosphoprotein complex in 32P-labeled, resting human platelets. Antibody
      probing of this complex detected hsc70, hsp90, two isoforms of the catalytic
      subunit of PP1, PP1C alpha and PP1C delta, as well as the M regulatory subunit of
      PP1 (PP1M). OA, at concentrations that markedly blocked platelet adhesion to
      collagen, caused hyperphosphorylation of the hsc70 complex. In platelets adhering
      to collagen, hsc70 was completely dephosphorylated and hsp90, PP1 alpha, and PP1M
      were dissociated from the complex, suggesting involvement of heat-shock proteins
      and protein phosphatases in platelet adhesion.

PMID- 9269770
TI  - Adenovirus-mediated transfer of tissue-type plasminogen activator augments
      thrombolysis in tissue-type plasminogen activator-deficient and plasminogen
      activator inhibitor-1-overexpressing mice.
AB  - Impaired fibrinolysis, resulting from increased plasminogen activator inhibitor-1
      (PAI-1) or reduced tissue-type plasminogen activator (t-PA) plasma levels, may
      predispose the individual to subacute thrombosis in sepsis and inflammation. The
      objective of these studies was to show that adenovirus-mediated gene transfer
      could increase systemic plasma t-PA levels and thrombolytic capacity in animal
      model systems. Recombinant adenovirus vectors were constructed that express
      either human wild type or PAI-1-resistant t-PA from the cytomegalovirus (CMV)
      promoter. Both t-PA-deficient (t-PA(-/-)) and PAI-1-overexpressing transgenic
      mice were infected by intravenous injection of these viruses. Intravenous
      injection of recombinant adenovirus resulted in liver gene transfer, t-PA
      synthesis, and secretion into the plasma. Virus dose, human t-PA antigen, and
      activity concentrations in plasma and extent of lysis of a 125I-fibrin-labeled
      pulmonary embolism were all closely correlated. Plasma t-PA antigen and activity
      were increased approximately 1,000-fold above normal levels. Clot lysis was
      significantly increased in mice injected with a t-PA-expressing virus, but not in
      mice injected with saline or an irrelevant adenovirus. Comparable levels of
      enzyme activity and clot lysis were obtained with wild type and inhibitor
      resistant t-PA viruses. Adenovirus-mediated t-PA gene transfer was found to
      augment clot lysis as early as 4 hours after infection, but expression levels
      subsided within 7 days. Adenovirus-mediated transfer of a t-PA gene can
      effectively increase plasma fibrinolytic activity and either restore (in t-PA
      deficient mice) or augment (in PAI-1-overexpressing mice) the thrombolytic
      capacity in simple animal models of defective fibrinolysis.

PMID- 9269771
TI  - Human immunodeficiency virus-1-tat protein induces the cell surface expression of
      endothelial leukocyte adhesion molecule-1, vascular cell adhesion molecule-1, and
      intercellular adhesion molecule-1 in human endothelial cells.
AB  - Human vascular endothelial cells (EC) have been implicated in the dissemination
      of human immunodeficiency virus type-1 (HIV-1). HIV-1-tat, a viral gene product
      essential for HIV replication, has been shown to interact with different cell
      types, altering their growth and inducing gene expression. In the present report,
      we have examined the effect of HIV-tat on the expression of various adhesion
      molecules in human umbilical vein EC. Our results show that treatment of EC with
      HIV-tat induces the cell surface expression of intercellular adhesion molecule-1,
      vascular cell adhesion molecule-1, and endothelial leukocyte adhesion molecule-1
      in a time- and dose-dependent manner. Cycloheximide abolished the HIV-tat
      dependent induction of all the adhesion molecules, indicating that protein
      synthesis was required for induction. The effect of HIV-tat on expression of
      adhesion molecules was potentiated by tumor necrosis factor (TNF), a well-known
      inducer of adhesion molecules. Like TNF, HIV-tat also enhanced the adhesion of
      human promyelomonocytic HL-60 cells to EC, and this effect was abolished by
      treatment with antibodies either against HIV-tat or adhesion molecules. Our
      results thus indicate that the HIV-tat protein can activate human vascular EC to
      induce the expression of various adhesion molecules that may play a role in the
      extravasation of HIV-infected cells.

PMID- 9269772
TI  - Anticoagulant effects of synthetic retinoids mediated via different receptors on
      human leukemia and umbilical vein endothelial cells.
AB  - We recently found that retinoic acids (RAs) exert anticoagulant effects by
      upregulating thrombomodulin (TM) and downregulating tissue factor (TF) expression
      in acute promyelocytic leukemia (APL) cells and monoblastic leukemia cells. Two
      classes of nuclear RA receptors, termed retinoic acid receptors (RARs) and
      retinoid X receptors, have been identified. Each receptor class consists of three
      subtypes. In the present study, we have used several synthetic retinoids to
      determine which receptor subtypes are involved in the regulation of TM and TF
      expression in NB4 APL cells, U937 monoblastic leukemia cells, and human umbilical
      vein endothelial cells (HUVECs). Am80, which has no binding affinity for RAR
      gamma, and Ch55, which does not bind to cytoplasmic retinoic acid binding protein
      (CRABP), upregulated TM and downregulated TF in NB4 and U937 cells, similar to
      all-trans RA (ATRA). A specific RAR alpha antagonist, Ro41-5253, significantly
      suppressed the upregulation of TM by ATRA and Am80 in NB4 cells, U937 cells, and
      HUVECs. In contrast, only with preincubation with both RAR alpha and RAR beta
      antagonists was downregulation of TF by retinoids suppressed in NB4 cells. These
      findings indicate that the mechanism of transactivation and transrepression
      functions of RARs are distinct and also elucidate the major role of RAR alpha in
      TM upregulation by retinoids in leukemic cells and HUVECs and the cooperation of
      RAR alpha and RAR beta in TF downregulation by retinoids. They also indicate that
      binding to CRABP is not required for the anticoagulant effect of retinoids and
      that synthetic retinoids will prove very useful in controlling distinct targets,
      the TM and TF genes, at the level of transcription, and will permit the
      development of retinoids with a new type of anticoagulant effect.

PMID- 9269773
TI  - A factor V genetic component differing from factor V R506Q contributes to the
      activated protein C resistance phenotype.
AB  - Factor V gene polymorphisms were investigated to detect components that may
      contribute to the activated protein C (APC) resistance phenotype in patients with
      venous thromboembolism. A specific factor V gene haplotype (HR2) was defined by
      six polymorphisms and its frequency was found to be similar in normal subjects
      coming from Italy (0.08), India (0.1), and Somalia (0.08), indicating that it was
      originated by ancestral mutational events. The relationship between the
      distribution of normalized APC ratios obtained with the functional assay and
      haplotype frequency was analyzed in patients heterozygous for factor V R506Q
      (factor V Leiden). The HR2 haplotype was significantly more frequent in patients
      with ratios below the 15th percentile than in those with higher ratios or in
      normal controls. Moreover, the study of 10 patients with APC resistance in the
      absence of the factor V R506Q mutation showed a 50-fold higher frequency of HR2
      homozygotes. The HR2 haplotype was associated with significantly lower APC ratios
      both in patients with venous thromboembolism and in age- and sex-matched
      controls. However, the two groups showed similar HR2 haplotype frequencies.
      Plasma mixing experiments showed that an artificially created double heterozygote
      for the factor V R506Q mutation and the HR2 haplotype had an APC ratio lower than
      that expected for a simple R506Q heterozygote. Time-course experiments evaluating
      the decay of factor V in plasma showed the normal stability of the molecule
      encoded by the factor V gene marked by the HR2 haplotype, which ruled out the
      presence of a pseudo-homozygous APC resistance mechanism. Our results provide new
      insights into the presence of factor V genetic components other than the factor V
      R506Q that are able to contribute to the APC resistance phenotype in patients
      with venous thromboembolism.

PMID- 9269774
TI  - Fluid shear stress modulates von Willebrand factor release from human vascular
      endothelium.
AB  - Fluid shear stress generated by blood flow on arterial wall may play a role in
      the process of atherosclerosis, not only affecting the mass transport phenomena
      that take place in blood, but also by modulation of synthesis and secretion of
      humoral factors released by vascular endothelium that mediate platelet-vessel
      wall interactions. The present study was designed to investigate whether shear
      stress, induced by laminar flow, modulates von Willebrand factor (vWF) release
      from cultured human umbilical vein endothelial cells (HUVEC) and whether this
      physical stimulation can affect vWF synthesis. Monolayers of HUVEC were exposed
      to laminar flow of varying magnitude (from 2 to 12 dynes/cm2) using a cone-and
      plate device. The release of vWF in cell supernatant and in extracellular matrix
      by cells exposed to flow or maintained in static conditions was evaluated by
      enzyme-linked immunosorbent assay. HUVEC exposed to laminar flow released higher
      amounts of vWF into the cell supernatant within few hours of exposure and vWF
      secretion was dependent on shear stress magnitude. vWF released in extracellular
      matrix was also higher in cell monolayers exposed to shear than in static
      controls. vWF mRNA expression in HUVEC was not affected by exposure of cells to
      laminar flow, indicating that shear-induced vWF release reflected enhanced
      secretion without de novo protein synthesis. Immunofluorescence studies showed
      that the release of vWF is due to exocytosis from Weibel-Palade bodies, the
      storage organelles of vWF. These data indicate a novel mechanism by which local
      hemodynamic shear forces modulate endothelial cell function and may play a role
      in development of arterial thrombotic events.

PMID- 9269775
TI  - Significance of RGD loop and C-terminal domain of echistatin for recognition of
      alphaIIb beta3 and alpha(v) beta3 integrins and expression of ligand-induced
      binding site.
AB  - Echistatin is a viper venom disintegrin containing RGD loop maintained by
      disulfide bridges. It binds with a high affinity to alpha(v) beta3 and alphaIIb
      beta3 and it induces extensive conformational changes in these integrins
      resulting in expression of ligand-induced binding site (LIBS) epitopes. We
      investigated the activities of echistatin and its three analogues (R24A, D27W,
      echistatin 1-41). R24A echistatin did not react with alphaIIb beta3 and alpha(v)
      beta3 integrins and did not cause LIBS effect. D27W echistatin showed increased
      binding to alphaIIb beta3 and decreased binding to alpha(v) beta3. This
      substitution impaired the ability of echistatin to induce LIBS in alpha(v) beta3
      integrin. Deletion of nine C-terminal amino acids of echistatin decreased its
      ability to bind alphaIIb beta3 and inhibit platelet aggregation. Truncated
      echistatin failed to induce LIBS epitopes on cells transfected with alphaIIb
      beta3 and alpha(v) beta3 genes. The ability of echistatin 1-41 to compete with
      binding of vitronectin to immobilized alpha(v) beta3 and monoclonal antibody 7E3
      to platelets and to VNRC3 cells was decreased, although this analogue, after
      immobilization, retained its ability to bind purified alpha(v) beta3. We propose
      a hypothesis in which echistatin's RGD loop determines selective recognition of
      alphaIIb beta3 and alpha(v) beta3 integrin, whereas the C-terminal domain
      supports its binding to resting integrin and significantly contributes to the
      expression of LIBS epitope and to conformational changes of the receptor, leading
      to a further increase of the binding affinity of echistatin and of the inhibitory
      effect.

PMID- 9269776
TI  - Anti-Sia-lb (anti-Gd) cold agglutinins bind the domain NeuNAc alpha2-3Gal in
      sialyl Lewis(x), sialyl Lewis(a), and related carbohydrates on nucleated cells
      and in soluble cancer-associated mucins.
AB  - Anti-Sia-lb (formerly anti-Gd) cold agglutinins (CAs) recognize sialylated
      carbohydrates on both adult and neonate red blood cells (RBCs). RBC CA activity
      inhibition experiments reported here indicate that the domain NeuNAc alpha2-3Gal,
      as found in sialyllactose, synthetic sialyl(s) Lewis(Le)(x) and sLe(a),
      sialyllactosamine, sialyl-fucosyllactose, and nonfucosylated sLe(a), constitutes
      the minimal epitope for these CAs, implicating that these autoantibodies could be
      able to bind this domain in sLe(x) and sLe(a) and related carbohydrates expressed
      on nucleated cells and in soluble cancer-related mucins. The following data
      obtained with the previously characterized monoclonal IgMk anti-Sia-lb CA, GAS,
      show that this is the case. GAS epitope expression among leukocytes that lack
      sLe(a) parallels that of sLe(x) determinant as detected by mouse monoclonal
      antibodies (MoAbs), especially MoAb KM-93. It is also found on epithelial
      malignant cells bearing both sLe(x) and sLe(a). GAS epitope on these nucleated
      cells, (1) like that present on RBC, is abolished by sialidase, unaffected by
      proteases, and inhibited by sialyllactose; and (2) is overlapping and/or proximal
      to that recognized by anti-sLe(x) MoAb, CSLEX-1, and KM-93. Moreover, CAGAS binds
      soluble cancer-associated mucins bearing sLe(x) and sLe(a) determinants. This
      binding is inhibited by sialyllactose and these mucins inhibit the RBC CA
      activity of CAGAS. The possible significance of anti-Sia-lb (anti-Gd) CAs as
      autoantibodies directed to carbohydrate ligands of host adhesion molecules that
      might be receptors of microbial adhesins of some CA-inducing pathogens is
      discussed.

PMID- 9269777
TI  - CD4 cross-linking (CD4XL) induces RAS activation and tumor necrosis factor-alpha
      secretion in CD4+ T cells.
AB  - CD4 molecules are the primary receptors for human immunodeficiency virus (HIV)
      and bind the envelope glycoprotein gp120 of HIV with high-affinity. We have
      previously shown that cross-linking of CD4 molecules (CD4XL) in normal peripheral
      blood mononuclear cells (PBMC) results in secretion of cytokines tumor necrosis
      factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), but not of interleukin
      2 (IL-2) or IL-4. To investigate the intracellular signaling events associated
      with CD4-gp120 interaction, we incubated CD4+ T cells from peripheral blood of
      HIV-negative healthy donors with HIV envelope protein gp160 alone or performed
      CD4XL with gp160 and anti-gp160 antibody. This procedure resulted in tyrosine
      phosphorylation of intracellular substrates p59fyn, zap 70, and p95vav and also
      led to ras activation, as assessed by conversion of rasGDP to rasGTP. The role of
      ras in CD4 signaling was further investigated using CD4+ Jurkat cells transfected
      with a dominant negative ras mutant. CD4+ T cells expressing dn-ras secreted
      significantly reduced levels of TNF-alpha in response to CD4XL. These studies
      indicate that interaction of HIV gp160 with CD4 molecules activates the ras
      pathway in T cells, which may result in the cells becoming unresponsive to
      subsequent stimulation.

PMID- 9269779
TI  - Role of A2a extracellular adenosine receptor-mediated signaling in adenosine
      mediated inhibition of T-cell activation and expansion.
AB  - Accumulation of adenosine and of deoxyadenosine in the absence of adenosine
      deaminase activity (ADA) activity results in lymphocyte depletion and in severe
      combined immunodeficiency (ADA SCID), which is currently explained by direct cell
      death-causing effects of intracellular products of adenosine metabolism. We
      explored the alternative mechanisms of peripheral T-cell depletion as due to
      inhibition of T-cell expansion by extracellular adenosine-mediated signaling
      through purinergic receptors. The strong inhibition of the T-cell receptor (TCR)
      triggered proliferation and of upregulation of interleukin-2 receptor alpha chain
      (CD25) molecules, but not the direct lymphotoxicity, were observed at low
      concentrations of extracellular adenosine. These effects of extracellular
      adenosine (Ado) are likely to be mediated by A2a receptor-mediated signaling
      rather than by intracellular toxicity of adenosine catabolites, because (1)
      poorly metabolized adenosine analogs cause the accumulation of cAMP and strong
      inhibition of TCR-triggered CD25 upregulation; (2) the A2a, but not the A1 or A3,
      receptors are the major expressed and functionally coupled adenosine receptors in
      mouse peripheral T and B lymphocytes, and the adenosine-induced cAMP accumulation
      in lymphocytes correlates with the expression of A2a receptors; (3) the specific
      agonist of A2a receptor, CGS21680, induces increases in [cAMP]i in lymphocytes,
      whereas the specific antagonist of A2a receptor, CSC, inhibits the effects of Ado
      and CGS21680; and (4) the increases in [cAMP]i mimic the adenosine-induced
      inhibition of TCR-triggered CD25 upregulation and splenocyte proliferation. These
      studies suggest the possible role of adenosine receptors in the regulation of
      lymphocyte expansion and point to the downregulation of A2a purinergic receptors
      on T cells as a potentially attractive pharmacologic target.

PMID- 9269778
TI  - Presentation of exogenous protein antigens on major histocompatibility complex
      class I molecules by dendritic cells: pathway of presentation and regulation by
      cytokines.
AB  - Several recent studies have shown that dendritic cells (DC) pulsed with soluble
      proteins can present peptide epitopes derived from these exogenous antigens on
      major histocompatability complex (MHC) class I molecules and induce an antigen
      specific cytotoxic T lymphocyte (CTL) response. We provide evidence here that DC
      use macropinocytosis to capture soluble antigens that are then presented on MHC
      class I molecules. The presentation of an epitope derived from soluble ovalbumin
      was transporter associated with antigen presentation (TAP)-dependent, brefeldin A
      sensitive, blocked by inhibitors of proteasomes, and resistant to chloroquine.
      These data suggest that exogenous antigens access the cytosol of DC and are
      proccessed for presentation via the same pathway described for conventional MHC
      class I-restricted cytosolic antigens. Proinflammatory mediators such as tumor
      necrosis factor-alpha (TNF-alpha) and lipopolysaccharide (LPS) reduced the
      efficiency of ovalbumin presentation via this pathway. This reduced presentation
      was not due to impaired expression of class I molecules because these substances
      upregulated the cell surface expression of Kb-molecules comparable to levels
      induced by interferon-gamma (IFN-gamma) treatment. The addition of IFN-gamma
      increased ovalbumin presentation even in the presence of TNF-alpha or LPS. These
      results show that DC might be involved in the cross-priming phenomenon. This
      could offer the immune system an additional pathway for effective priming of
      cytotoxic T cells and provide the possibility to activate both CD4 and CD8 T-cell
      responses.

PMID- 9269780
TI  - T helper 2-dominant antilymphoma immune response is associated with fatal
      outcome.
AB  - The precise role of the endogenous immune system in modulating cancer development
      remains unclear. Tumor cells are generally thought to be nonimmunogenic because
      they are of 'self' origin. However, tumor-reactive lymphocytes can be isolated
      from patients with many types of cancer. It is unclear what role these
      lymphocytes play and why they fail to protect the host. Using a murine B-cell
      leukemia/lymphoma (BCL1) model, we showed the development of a vigorous antitumor
      T-cell response in the tumor-susceptible host. Specific T-cell responses against
      BCL1 developed as early as day 4. However, the nature of this nonprotective
      response is different from the protective response produced in a major
      histocompatibility complex-matched tumor-resistant host. Susceptible hosts
      developed a T helper 2 (Th2)-dominant response, whereas resistant hosts developed
      a Th1-dominant response to BCL1. Cytolytic activity against BCL1 developed in
      both resistant and susceptible hosts, but in the susceptible host, this response
      was weaker and delayed compared with that in the resistant host. Thus, tumor
      susceptibility does not necessarily mean the absence of an antitumor immune
      response. Rather, the nature of the antitumor immune response is critical in
      determining clinical outcome.

PMID- 9269781
TI  - A role for T-helper type-1 and type-2 cytokines in the regulation of human
      monocyte apoptosis.
AB  - T-helper type-1 (Th1) and type-2 (Th2) cytokines, respectively, favor T-cell
      mediated immunity and defense against intracellular pathogens or antibody
      mediated immunity and defense against extracellular pathogens. Here we report
      that type-1 and type-2 cytokines also exert a regulatory effect on human monocyte
      survival. Interleukin-12 (IL-12) enhanced survival in long-term (10 days)
      cultures of adherent monocytes, whereas IL-10 induced death by apoptosis. In
      short-term cultures (2 days), the Th2 cytokines, IL-10 and IL-4, enhanced
      apoptosis; however, the Th1 cytokines, IL-12 and IL-2 only showed a reducing
      effect on monocyte apoptosis in culture conditions that decreased monocyte
      adhesion leading to increased levels of spontaneous apoptosis; finally, the Th1
      cytokine, interferon-gamma (IFN-gamma), acted in a dose-dependent fashion: At
      high concentrations, IFN-gamma enhanced apoptosis, which is an effect related to
      IL-10 secretion and reduced by antibodies to IL-10. Th1 cytokines reduced
      monocyte apoptosis induced by several stimuli: IL-2 reduced apoptosis induced by
      either IL-10 or high concentrations of IFN-gamma, IL-12 reduced apoptosis induced
      by either the ligation of the Fas (CD95) molecule or gamma-irradiation, and IFN
      gamma (at low doses that did not trigger apoptosis) reduced apoptosis induced by
      gamma-irradiation. These findings suggest that the regulatory role of type-1 and
      type-2 cytokines on the development of immune responses and inflammatory
      reactions also involves the regulation of monocyte death by apoptosis.

PMID- 9269782
TI  - Contact between human bone marrow stromal cells and B lymphocytes enhances very
      late antigen-4/vascular cell adhesion molecule-1-independent tyrosine
      phosphorylation of focal adhesion kinase, paxillin, and ERK2 in stromal cells.
AB  - Contact with bone marrow stromal cells is crucial for the normal growth and
      development of B-cell precursors. We have previously shown that human bone marrow
      stromal cell tyrosine kinase activity can be activated by direct contact with B
      lymphoid cells (J Immunol 155:2359, 1995). In the present study, we show that
      increased tyrosine phosphorylation of focal adhesion kinase, paxillin, and
      extracellular-related kinase 2 (or p42 MAP kinase) accounted for the major
      changes occurring in stromal cell tyrosine phosphorylation after 5 to 10 minutes
      of contact with the RAMOS B-lymphoma cell line. Although adhesion of B-cell
      precursors to stromal cells is primarily mediated by very late antigen-4 (VLA-4)
      and vascular cell adhesion molecule-1 (VCAM-1), VLA-4-deficient and adhesion
      deficient RAMOS cells were equally capable of stimulating stromal cell tyrosine
      phosphorylation. Similar changes in the tyrosine phosphorylation pattern of
      stromal cells were induced by contact with normal human B-cell precursors and
      several other B-lineage cell lines. After 5 to 30 minutes of contact with stromal
      cells, no change in protein tyrosine phosphorylation was detected in RAMOS or
      normal human B-cell precursors removed from stromal cells. Pretreatment of
      stromal cells with cytochalasin D abrogated contact-mediated enhancement of
      stromal cell tyrosine phosphorylation, suggesting that an intact cytoskeleton was
      essential. These results suggest that B-cell contact activates stromal cell
      signaling cascades that regulate cytoskeletal organization and transcription,
      independent of the interaction mediated by VLA-4 and VCAM-1.

PMID- 9269783
TI  - Demonstration of frequent occurrence of clonal T cells in the peripheral blood of
      patients with primary cutaneous T-cell lymphoma.
AB  - Clonal T cells have been demonstrated in skin lesions of all stages of cutaneous
      T-cell lymphomas (CTCLs). However, there are conflicting data regarding the CTCL
      stage at which dissemination of clonal cells into peripheral blood occurs.
      Although the multifocal occurrence of cutaneous CTCL lesions and T-cell
      recirculation suggest an early appearance of neoplastic cells in the blood,
      circulating clonal T cells have only been detected in advanced stages. We
      investigated their occurrence by a highly sensitive polymerase chain reaction
      (PCR) assay amplifying T-cell receptor gamma rearrangements and subsequent
      heteroduplex temperature gradient gel electrophoresis (HD-TGGE) of the
      amplification products. Circulating clonal T cells were found in 26 of 45
      patients with mycosis fungoides (MF), six of seven with Sezary's syndrome (SS),
      10 of 13 pleomorphic CTCLs, and three of four unclassified CTCLs. Corresponding
      skin specimens carried clonal T cells in 29 of 40 MF, three of four SS, 12 of 12
      pleomorphic, and two of two unclassified CTCL patients. Except for the blood
      specimen of a psoriatic patient, all samples of 60 controls (psoriasis vulgaris,
      atopic dermatitis, and healthy volunteers) revealed polyclonal amplification
      products. In 30 of 32 CTCL patients carrying a clonal rearrangement in blood and
      skin, identity of both clones was indicated by HD-TGGE and confirmed by
      sequencing six of these cases. We found an unexpected high frequency of identical
      clonal T cells in peripheral blood and skin of CTCL patients, including early
      stages of MF. This supports the concept of an early systemic disease in CTCL and
      raises new questions concerning the pathogenesis.

PMID- 9269785
TI  - Metalloproteinases in multiple myeloma: production of matrix metalloproteinase-9
      (MMP-9), activation of proMMP-2, and induction of MMP-1 by myeloma cells.
AB  - Multiple myeloma is a very devastating cancer with a high capacity to destroy
      bone matrix. Matrix metalloproteinases (MMPs) play a critical role in bone
      remodeling and tumor invasion. In this study, we have investigated the
      involvement of interstitial collagenase (MMP-1) and gelatinases (MMP-2 and MMP-9)
      in the biology of multiple myeloma. We show (1) that myeloma cells express MMP-9
      and (2) that this expression is not subjected to regulation either by interleukin
      6 (IL-6), the major myeloma cell growth factor, or by other cytokines involved in
      the multiple myeloma cytokine network. In the tumoral environment, we show that
      bone marrow stromal cells express MMP-1 and MMP-2. Whereas MMP-1 is positively
      regulated by IL-1beta, tumor necrosis factor-alpha, and Oncostatin M, MMP-2 is
      not modulated by any of these cytokines. To evaluate whether myeloma cells can
      modify the bone marrow stromal environment, we have examined these MMP activities
      in coculture. Interestingly, we have observed an upregulation of MMP-1 and a
      partial conversion of the proMMP-2 into its activated form. We conclude that the
      increase of MMP activity produced or induced by myeloma cells in these cocultures
      could favor bone resorption and tumor invasion. Inhibition of such activities
      could represent a new therapeutical approach in multiple myeloma.

PMID- 9269784
TI  - Expression of the neural cell adhesion molecule CD56 is associated with short
      remission duration and survival in acute myeloid leukemia with t(8;21)(q22;q22).
AB  - Although acute myeloid leukemia (AML) with t(8;21) (q22;q22) is associated with a
      high complete remission (CR) rate and prolonged disease-free survival, treatment
      outcome is not universally favorable. Identifying factors that predict for
      treatment outcome might allow therapy to be optimized based on risk. AML with
      t(8;21) has a distinctive immunophenotype, characterized by expression of the
      myeloid and stem cell antigens CD13, CD15, CD34, and HLADr, and frequent
      expression of the B-cell antigen CD19 and the neural cell adhesion molecule CD56,
      a natural killer cell/stem cell antigen. Because CD56 expression has been
      associated with both extramedullary leukemia and multidrug resistance, we sought
      to correlate CD56 expression with treatment outcome in AML with t(8;21).
      Pretreatment leukemia cells from 29 adult de novo AML patients with t(8;21)
      treated on Cancer and Leukemia Group B (CALGB) protocols were immunophenotyped by
      multiparameter flow cytometry as part of a prospective immunophenotyping study of
      adult AML (CALGB 8361). CD56 was expressed in 16 cases (55%). There was no
      correlation between CD56 expression and age, sex, white blood cell count,
      granulocyte count, the presence of additional cytogenetic abnormalities, or the
      presence of extramedullary disease at diagnosis. The CR rate to standard-dose
      cytarabine and daunorubicin was similar for cases with and without CD56
      expression (88% v 92%; P = 1.0). Post-CR therapy included at least one course of
      high-dose cytarabine in 24 of 26 patients who achieved CR; numbers of courses
      administered were similar in cases with and without CD56 expression. Although
      post-CR therapy did not differ, CR duration was significantly shorter in cases
      with CD56 expression compared with those without (median, 8.7 months v not
      reached; P = .01), as was survival (median, 16.5 months v not reached; P = .008).
      We conclude that CD56 expression in AML with t(8;21) is associated with
      significantly shorter CR duration and survival. Our results suggest that CD56
      expression may be useful in stratifying therapy for this subtype of AML.

PMID- 9269786
TI  - Association of PML-RAR alpha fusion mRNA type with pretreatment hematologic
      characteristics but not treatment outcome in acute promyelocytic leukemia: an
      intergroup molecular study.
AB  - In each case of acute promyelocytic leukemia (APL) one of three PML-RAR alpha
      mRNA types is produced, depending on the break/fusion site in the PML gene that
      is linked to a common RAR alpha gene segment: a short (S)-form type, PML exon 3
      RAR alpha exon 3; a long (L)-form type, PML exon 6 RAR alpha exon 3; or a
      variable (V)-form type, variably deleted PML exon 6 RAR alpha exon 3. We
      evaluated whether PML-RAR alpha mRNA type is associated with distinct
      pretreatment clinical characteristics and therapeutic outcome in previously
      untreated adult APL patients registered to protocol INT 0129 by the Eastern
      Cooperative Oncology Group, the Southwest Oncology Group, and the Cancer and
      Leukemia Group B. Of 279 clinically eligible cases, 230 were molecularly
      evaluable, and of these, 111 were randomized to receive remission induction
      therapy with all-trans retinoic acid (ATRA) and 119 with conventional
      chemotherapy. Nine cases not excluded by central pathology review were PML-RAR
      alpha negative, and notably, none of five of these cases treated with ATRA
      achieved complete remission (CR). Among 221 PML-RAR alpha-positive cases, there
      were 82 S-form cases (37%), 121 L-form cases (55%), and 18 V-form cases (8%).
      Before any antileukemic therapy, the S-form type, compared with the L-form type,
      was associated with higher values for the white blood cell (WBC) count (median
      2,500/microL v 1,600/microL; P = .009), the percentage of blood blasts plus
      promyelocytes (median 29% v 8.5%; P = .03), and the absolute blood blasts plus
      promyelocytes (884/microL v 126/microL; P = .019). Also, an increased percentage
      of S-form versus L-form cases had the M3 variant phenotype, 24% v 12% (P = .036).
      There were no differences between S-form and L-form cases in either CR rate (79%
      v 69%; P = .14) or disease free survival distribution (multivariate analysis
      adjusting for the association of S-form type and higher WBC count; P = .40). We
      conclude that the S-form type is associated with previously-identified adverse
      risk WBC parameters but that the identification of the S-form or L-form type of
      PML-RAR alpha mRNA, per se, does not predict clinical outcome or add to the value
      of an increased WBC count as a negative prognostic indicator in APL patients.

PMID- 9269787
TI  - Immunohistochemical detection of the Epstein-Barr virus-encoded latent membrane
      protein 2A in Hodgkin's disease and infectious mononucleosis.
AB  - We describe two new monoclonal antibodies specific for the Epstein-Barr virus
      (EBV)-encoded latent membrane protein 2A (LMP2A) that are suitable for the
      immunohistochemical analysis of routinely processed paraffin sections. These
      antibodies were applied to the immunohistochemical detection of LMP2A in
      Hodgkin's disease (HD). LMP2A-specific membrane staining was seen in the Hodgkin
      and Reed-Sternberg (HRS) cells of 22 of 42 (52%) EBV-positive HD cases, but not
      in 39 EBV-negative HD cases. In lymphoid tissues from patients with acute
      infectious mononucleosis (IM), interfollicular immunoblasts were shown to express
      LMP2A. This is the first demonstration of LMP2A protein expression at the single
      cell level in EBV-associated lymphoproliferations in vivo. The detection of LMP2A
      protein expression in HD and IM is of importance in view of the proposed role of
      this protein for maintaining latent EBV infection and its possible contribution
      for EBV-associated transformation. Because LMP2A provides target epitopes for EBV
      specific cytotoxic T cells, the expression of this protein in HRS cells has
      implications for the immunotherapeutic approaches to the treatment of HD.

PMID- 9269788
TI  - Downregulation of the proinflammatory cytokine response to endotoxin by
      pretreatment with the nontoxic lipid A analog SDZ MRL 953 in cancer patients.
AB  - Interfering with the endotoxin-mediated cytokine cascade is thought to be a
      promising approach to prevent septic complications in gram-negative infections.
      The synthetic lipid A analog SDZ MRL 953 has been shown to be protective against
      endotoxic shock and bacterial infection in preclinical in vivo models. As part of
      a trial of unspecific immunostimulation in cancer patients, we conducted a double
      blind, randomized, vehicle-controlled phase I trial of SDZ MRL 953 to
      investigate, first, its biologic effects and safety of administration in humans
      and, second, its influence on reactions to a subsequent challenge of endotoxin
      (Salmonella abortus equi). Twenty patients were treated intravenously with
      escalating doses of SDZ MRL 953 or vehicle control, followed by an intravenous
      application of endotoxin (2 ng/kg of body weight [BW]). Administration of SDZ MRL
      953 was safe and well-tolerated. SDZ MRL 953 itself increased granulocyte counts
      and serum levels of granulocyte colony-stimulating factor (G-CSF) and interleukin
      6 (IL-6), but not of the proinflammatory cytokines tumor necrosis factor-alpha
      (TNF-alpha), IL-1beta, and IL-8. Compared with vehicle control, pretreatment with
      SDZ MRL 953 markedly reduced the release of TNF-alpha, IL-1beta, IL-8, IL-6, and
      G-CSF, but augmented the increase in granulocyte counts to endotoxin. Induction
      of tolerance to the endotoxin-mediated cascade of proinflammatory cytokines by
      pretreatment with SDZ MRL 953 in patients at risk may help to prevent
      complications of gram-negative sepsis.

PMID- 9269789
TI  - Influence of pH on phospholipid redistribution in human erythrocyte membrane.
AB  - The influence of the suspension pH (pHo) on the transmembrane mobility of spin
      labeled phospholipid analogues in the human red blood cell was investigated. The
      passive transverse diffusion of spin-labeled phospholipid analogues was
      independent of pHo in the investigated range (5.8 to 8.5). However, upon
      acidification to pHo 5.8, a significant decrease of the rapid adenosine
      triphosphate (ATP)-dependent inward movement of aminophospholipids was found at
      physiologic ionic concentration, whereas a change of pH from 7.4 to 8.5 did not
      affect this transport. Evidence is given that the intracellular pH affects the
      active transport of aminophospholipids but not the extracellular pH. Suppression
      of the ATP-dependent outside-inside redistribution of aminophospholipid analogues
      by low pH was reversible because original transport activity was re-established
      upon reneutralization. pH dependence of the active phospholipid transport was not
      caused by the spin-labeled reporter group or by depletion of intracellular ATP.
      Because the same influence of pH on aminophospholipid movement could be observed
      for resealed ghosts, constituents of the red blood cell cytoplasm do not mediate
      the influence of pH on the ATP-dependent inward movement of aminophospholipids.

PMID- 9269790
TI  - Allogeneic peripheral blood progenitor cell transplantation in a murine model:
      evidence for an improved graft-versus-leukemia effect.
AB  - Peripheral blood progenitor cells (PBPCs) are increasingly being used to replace
      bone marrow cells (BMCs) as a source of hematopoietic stem cells also in the
      field of allogeneic transplantation. Whereas it is well known that PBPC grafts
      and BM differ significantly in progenitor cell content and lymphocyte dose, the
      clinical consequences of these differences with respect to engraftment, graft
      versus-host disease (GVHD), and the graft-versus-leukemia (GVL) effect are more
      difficult to assess. We present a murine model that allows us to evaluate
      engraftment, GVHD, and GVL effect of allogeneic PBPC transplantation (PBPCT).
      Balb/c mice (H-2d) served as recipients. Donors were major histocompatibility
      complex-matched DBA/2 mice or syngeneic Balb/c mice, respectively. Experiments
      with increasing numbers of BMCs or Filgastrim-mobilized PBPCs showed that the
      number of progenitor cells in the graft was correlated with the probability to
      engraft, irrespective of the graft type. With identically high cell numbers
      transferred (1 x 10(9) nucleated cells/kg body weight [BW]), the mortality rates
      due to GVHD (25%) were about the same after allogeneic BM transplantation (BMT)
      and allogeneic PBPCT, although PBPC grafts contained four times more CD3+ T cells
      as compared with BM grafts (6.2 x 10(8) v 1.4 x 10(8)/kg BW). For investigation
      of GVL activity, Balb/c recipients were injected with syngeneic cells of the B
      lymphocytic leukemia cell line A20 2 days before transplantation. After total
      body irradiation to a dose of 7.5 Gy, 1 x 10(9)/kg BW Balb/c PBPCs, DBA BMCs, or
      DBA PBPCs were infused. The relapse rates observed were 80% after syngeneic PBPCT
      (n = 22), 60% after allogeneic BMT (n = 23), and 34% after allogeneic PBPCT (n =
      26) (allogeneic BMT v PBPCT, P = .032). We conclude that transplantation of
      allogeneic PBPCs instead of BM may enhance the GVL effect without an increase of
      GVHD.

PMID- 9269791
TI  - Normal immunologic response to a neoantigen, bacteriophage phiX-174, in baboons
      with long-term lymphohematopoietic reconstitution from highly purified CD34+ Lin-
      allogeneic marrow cells.
AB  - The CD34 antigen is thought to be expressed by hematopoietic stem cells in adult
      humans and nonhuman primates. We present data that baboons transplanted with
      highly purified allogeneic CD34+ marrow cells devoid of detectable mature and
      immature T and B lymphocytes and myeloid cells, isolated from sex-mismatched
      mixed lymphocyte culture (MLC) nonreactive siblings, have maintained stable
      lymphohematopoietic engraftment with donor cells for greater than 4.9, greater
      than 6.0, and 5.0 years. Cytogenetic analysis of unfractionated marrow and
      peripheral blood cells at multiple time points after transplantation show
      virtually all donor cells in two animals and stable mixed chimerism in the third.
      We used polymerase chain reaction to show that colony-forming unit-granulocyte
      macrophage, burst-forming unit-erythroid, and high proliferative potential colony
      forming cells (HPP-CFC) were virtually all of donor origin in two animals and
      present at lower levels in the stable mixed chimera. CD20+ B-lymphoblastoid cell
      lines derived by Herpesvirus Papio transformation of peripheral blood cells were
      virtually all donor in two animals and 50% donor in the mixed chimera. CD4+ and
      CD8+ T cells and neutrophils purified from the peripheral blood of the two female
      animals also were all donor-derived. To assess immunologic function after
      transplantation, we immunized the three long-term chimeric animals and two normal
      control animals with bacteriophage phiX-174, a neoantigen that requires the
      interaction of antigen-presenting cells, T lymphocytes, and B lymphocytes to
      mount a normal antibody response. Experimental and control animals, when
      immunized with bacteriophage, had similar serum Ig levels. The experimental and
      control animals generated similar titers of antibacteriophage antibodies after
      primary and secondary immunizations with evidence of amplification and class
      switching. These findings further support the hypothesis that the CD34+ antigen
      is expressed on hematopoietic stem cells that can mediate stable long-term
      lymphohematopoiesis in vivo and, importantly, that normal immunologic function
      can be reconstituted in vivo after transplantation of the highly purified CD34+
      Lin- cells alone.

PMID- 9269792
TI  - Congenital haptoglobin deficiency.

PMID- 9269793
TI  - Evidence that the RHD(VI) deletion genotype does not exist.

PMID- 9269794
TI  - The A20210 allele of the prothrombin gene is not frequently associated with the
      factor V Arg 506 to Gln mutation in thrombophilic families.

PMID- 9269795
TI  - NPM-ALK gene fusion and Hodgkin's disease.

PMID- 9269796
TI  - Blood on filter paper as a readily available source of bcr-abl rearranged mRNA.

PMID- 9269797
TI  - Mismatched platelet transfusions to alloimmunized patients.

PMID- 9269798
TI  - Hemoglobin E and pyrimidine 5' nucleotidase deficiency.

PMID- 9269799
TI  - Responses of granulocyte colony-stimulating factor-mobilized peripheral blood
      mononuclear cells to alloantigen stimulation.

PMID- 9269801
TI  - Splenomegaly, eosinophilia, and pruritus: Hodgkin's disease, or...?

PMID- 9269800
TI  - Disruption of a long-range disulfide bond between residues Cys406 and Cys655 in
      glycoprotein IIIa does not affect the function of platelet glycoprotein IIb-IIIa.

PMID- 9269802
TI  - Bilateral gluteoplasty for fecal incontinence.
AB  - PURPOSE: This study describes our clinical experience with adynamic bilateral
      gluteoplasty in 20 patients with total fecal incontinence, in whom a sphincter
      repair had failed (n = 17) or was nonviable. METHODS: Between 1986 and 1995, 12
      women and 8 men ranging in age from 15 to 58 (mean, 37) years underwent different
      techniques of adynamic gluteoplasty. The indications for the operation were
      congenital anomalies, denervation, or sphincter destruction. Postoperative
      evaluation was clinical (Pescatori grading; self-evaluation) and manometric.
      RESULTS: Morbidity was only related to wound infection (n = 7) requiring late
      reoperations for neosphincter repair (n = 5), anal stenosis (n = 2), and
      incisional hernia after colostomy closure (n = 1). Two other patients with no
      complications also had further surgery for tightening of the neosphincter; they
      had a successful outcome. Of the 17 evaluable patients, 9 (53 percent) achieved
      normal control or were graded as Pescatori A-1, A-2, B-1, or C-1, 1 (6 percent)
      as Pescatori C-2, and 7 (41 percent) as Pescatori C-3. Six patients (35 percent)
      judged their results as excellent, three (18 percent) as good, one (6 percent) as
      fair, and seven (41 percent) as bad. Eight patients are able to retain 200 ml of
      water instilled into the rectum for between five minutes and two hours. For the
      nine patients with better results, the mean +/- standard deviation of the
      differences between postgluteoplasty and pregluteoplasty anal pressures were 40
      +/- 25 mmHg (resting pressure) and 122 +/- 85 mmHg (squeeze pressure). These
      findings demonstrate a tonic and voluntary activity of the plasty. The author's
      technique has less morbidity, and excellent or good results were achieved in 67
      percent of the patients. Failures were attributable to suture disruption (n = 4),
      poor muscular contraction (n = 2), and intractable constipation (n = 1).
      CONCLUSIONS: Adynamic gluteoplasty is efficient for achieving good or very good
      continence status in a higher proportion of patients than with other adynamic
      muscle transfer procedures.

PMID- 9269803
TI  - Biofeedback retraining in patients with functional constipation and paradoxical
      puborectalis contraction: comparison of anal manometry and sphincter
      electromyography for feedback.
AB  - PURPOSE: This study was undertaken to assess the effect of biofeedback therapy in
      patients with constipation and paradoxical puborectalis contraction and to
      compare two different feedback modes. METHODS: Twenty-six patients were randomly
      allocated to either of two feedback modes: anal pressure using a manometry probe
      or anal sphincter electromyography (EMG) using surface electrodes. RESULTS: Six
      patients were unable to complete their training; ten patients were retrained
      using anal manometry and ten patients using EMG. The paradoxical puborectalis
      contraction disappeared after retraining with manometry feedback in eight of ten
      patients and with EMG feedback in ten of ten patients. A significant improvement
      in both bowel function and abdominal symptoms was found after training and a
      continued improvement at follow-up six months later. Six patients in the
      manometry group and nine in the EMG group experienced an overall improvement in
      symptoms. The two feedback methods did not differ in terms of efficacy.
      CONCLUSIONS: Our results suggest that biofeedback, using either manometry or EMG,
      is effective in improving symptoms and anorectal function caused by paradoxical
      puborectalis contraction.

PMID- 9269804
TI  - Are special investigations of value in the management of patients with fecal
      incontinence?
AB  - PURPOSE: The aim of this study was to determine whether special investigations
      significantly alter either the diagnosis or the management plan of patients with
      fecal incontinence assessed on the basis of a structured history and physical
      examination alone. METHODS: Fifty consecutive patients with fecal incontinence
      were prospectively studied in a tertiary referral clinic. Each patient was
      assessed by two clinicians who independently formulated a diagnosis and treatment
      plan based on the history and physical examination. The resulting 100 patient
      assessments were then compared with the final diagnosis and treatment plan
      formulated on completion of endoanal ultrasound, anal manometry, external
      sphincter electromyography, and defecating proctography. RESULTS: In the
      assessment of fecal incontinence, the addition of special investigations altered
      the diagnosis of the cause of incontinence based on history and examination alone
      in 19 percent of cases. The management plan was altered in 16 percent of cases.
      Special investigations were most useful in separating neuropathy from rectal wall
      disorders and in demonstrating the unexpected presence of internal sphincter
      defects and neuropathy. CONCLUSIONS: Even experienced colorectal surgeons will
      misdiagnose up to one-fifth of patients presenting with fecal incontinence if
      assessment is based on the history and physical examination alone. However
      surgically correctable causes of incontinence are rarely missed on clinical
      assessment.

PMID- 9269805
TI  - Symptoms in chronic constipation.
AB  - OBJECTIVES: This study was designed to evaluate whether detailed symptom analysis
      would help to identify pathophysiologic subgroups in chronic constipation.
      METHODS: In 190 patients with chronic constipation (age, 53 (range, 18-88) years;
      85 percent of whom were women), symptom evaluation, transit time measurement
      (radiopaque markers), and functional rectoanal evaluation (proctoscopy, anorectal
      manometry, defecography) were performed. Patients were classified on the basis of
      objective data from all tests in four different groups ("disordered defecation,"
      "slow gastrointestinal transit," "disordered defecation combined with slow
      transit stool," and "no pathologic finding"). RESULTS: In 59 percent of patients,
      disordered defecation was found, and 27 percent had slow-transit stool. In 6
      percent of patients, a combination of both was found; in only 8 percent of
      patients, there were no pathologic findings. Straining was reported by the vast
      majority in all groups (82-94 percent). Infrequent bowel movements and abdominal
      bloating were more common in slow-transit stool (87 and 82 percent vs. 69 and 55
      percent, respectively; both P < 0.01). Feeling of incomplete evacuation was more
      common in disordered defecation (84 vs. 46 percent; P < 0.0001). However,
      specificity of these symptoms was discouraging (for slow-transit stool:
      infrequent bowel movements had a sensitivity of 87 percent and a specificity of
      32 percent and abdominal bloating had a sensitivity of 82 percent and specificity
      of 45 percent; for disordered defecation: feeling of incomplete evacuation had a
      sensitivity of 84 percent and a specificity of 54 percent). Only the sense of
      obstruction and digital maneuvers were acceptably specific (79 and 85 percent,
      respectively) for disordered defecation, but sensitivity was low. CONCLUSIONS:
      Definition of chronic constipation by infrequent bowel movements alone is of
      little value; the symptom "necessity to strain" is much better suited (94 percent
      sensitivity). Specificity of infrequent bowel movements for slow-transit stool
      was discouraging. Sense of obstruction and digital manipulation for evacuation
      are relatively specific for disordered defecation but insensitive. Therefore,
      symptoms of chronically constipated patients are not well suited to differentiate
      between the pathophysiologic subgroups suffering chronic constipation.

PMID- 9269806
TI  - Electromyographic assessment of biofeedback training for fecal incontinence and
      chronic constipation.
AB  - INTRODUCTION: Biofeedback training is an effective modality for the treatment of
      chronic constipation and fecal incontinence. In general, patients express
      satisfaction and perceive functional improvement following biofeedback therapy;
      however, quantifying these observations has been difficult. AIM: This study was
      undertaken to evaluate the physiologic benefits of biofeedback therapy as
      reflected by noninvasive electromyography parameters. METHODS: Fifty-five
      patients who underwent computerized electromyography-based biofeedback treatment
      at our institution between July 1993 and July 1995 were identified. Noninvasive
      electromyographic testing was performed before, during (weekly), and at
      completion of training. Mean number of weekly sessions was seven (range, 5-11).
      Short-term and ten-second contractions (amplitude/microV), sustained contractions
      (endurance, in seconds), and net strength (microV) of the external anal sphincter
      before and after biofeedback were compared for differences. RESULTS: There were
      30 patients with chronic constipation, mean age, 65.3 (range, 33-86) years,
      composed of 24 women, and 25 patients with fecal incontinence, mean age 66
      (range, 34-85) years, composed of 12 males. Statistically significant improvement
      in endurance and net strength following biofeedback training was noted in both
      the constipated and the fecal incontinence groups. Fifty-three of 55 (96.4
      percent) patients expressed 50 to 100 percent subjective satisfaction after
      biofeedback therapy. Forty-six of 55 (83.6 percent) patients demonstrated
      individually improved endurance. CONCLUSIONS: Sphincter endurance and net
      strength, as measured by noninvasive electromyography, significantly improve
      following biofeedback therapy in both constipated and fecal incontinence
      patients. These data suggest that endurance and net strength may be useful tools
      in assessing a benefit from biofeedback training in these patients.

PMID- 9269807
TI  - Perianal Bowen's disease: associated tumors, human papillomavirus, surgery, and
      other controversies.
AB  - BACKGROUND: Perianal Bowen's disease (BD) is an intraepithelial nonkeratinizing
      carcinoma, associated historically with internal tumors. METHODS: A review of
      patients with perianal BD presenting consecutively during a 25-year span was
      undertaken, excluding Bowenoid papulosis and contiguous genital BD. Histologic
      slides were resubmitted for review by an experienced pathologist, in a "blind"
      fashion among other slides. Follow-up was updated in every patient. Survival and
      recurrence curves were generated by the Kaplan-Meier method and were compared
      with a normal age-matched population (log-rank test). RESULTS: Nineteen patients
      were identified; 15 of them were females. Mean age +/- standard deviation was
      49.6 +/- 10.6 years. Five patients had a coincidental diagnosis (hemorrhoidectomy
      or wart excision). No associated carcinomas were found; however, eight patients
      had isolated BD of the vulva. Eleven patients had a history of anal warts,
      cervical/vulvar dysplasia, or both. Wide resection, including V-Y flaps, was
      performed in 18 patients without dysfunction. One-year and five-year recurrence
      was 16 and 31 percent. Recurrence was treated in all but one case by wider
      resection. Mean follow-up was 8.4 years. Five-year survival was 75 percent, lower
      than the matched population (P = 0.001); however, only one death was related to
      BD. CONCLUSIONS: Perianal BD has no association with internal tumors. Despite a
      high rate of recurrence, perianal BD can be treated by local excision. An
      increased rate of human papilloma virus-related entities was found, which could
      suggest a causative role.

PMID- 9269808
TI  - Colposcopic appearance of anal squamous intraepithelial lesions: relationship to
      histopathology.
AB  - PURPOSE: The incidence of anal cancer is increased in men with a history of anal
      receptive intercourse. Analogous to cervical cancer, whose precursor is cervical
      high-grade squamous intraepithelial lesion (HSIL), anal cancer may be preceded by
      anal HSIL. Although not yet proven, detection, follow-up, and treatment of HSIL
      may prevent development of anal cancer. Cervical colposcopic methodology was used
      to describe anal lesions and to determine if HSIL could be distinguished from low
      grade squamous intraepithelial lesion (LSIL). METHODS: The colposcopic
      characteristics of 385 biopsied anal lesions were described and correlated with
      results of histopathology in a cohort of 121 human immunodeficiency virus
      positive and 31 human immunodeficiency-negative homosexual/bisexual men with anal
      lesions followed as part of a longitudinal study of anal squamous intraepithelial
      lesions. Color, contour, surface, and vascular patterns of anal lesions were
      analyzed and correlated with histologic diagnosis. RESULTS: Sixty-seven percent
      of biopsies showed LSIL and 26 percent showed HSIL. The positive predictive value
      for anal HSIL in lesions with characteristics typical of cervical LSIL was 7.7
      percent (95 percent confidence interval, 1.8-14), whereas the positive predictive
      value for anal HSIL in lesions with characteristics typical of cervical HSIL was
      49 percent (95 percent confidence interval, 40-58). CONCLUSIONS: The colposcopic
      appearance of different grades of anal squamous intraepithelial lesions was
      similar to those described for the cervix. Incorporation of colposcopy into
      assessment of anal disease could aid in distinguishing anal LSIL from HSIL.

PMID- 9269809
TI  - Long-term survival after treatment of malignant colonic polyps.
AB  - PURPOSE: This study was designed to evaluate the long-term outcome and survival
      of patients treated for malignant colonic polyps. METHODS: A retrospective review
      of 15,975 cases of colonoscopies with 8,685 endoscopic polypectomies performed
      between 1972 and 1990 was undertaken. In 65 patients, the polypectomy specimens
      contained invasive carcinoma. Six patients were excluded (follow-up, <6 months).
      Polyp data, operative findings, and follow-up on the remaining 59 patients were
      recorded. RESULTS: Malignant polyps were found in 35 males and 24 females who had
      an average age of 64 (range, 39-81) years. Follow-up ranged from 12 to 202 (mean,
      90) months. Tumor differentiation was poor in one and well or moderately
      differentiated in 58 patients. Positive or indeterminate margins were found in 13
      patients. Thirty-seven (63 percent) patients were managed with polypectomy and
      surveillance. Four of these (with rectal tumors) also had an additional local
      excision for questionable margins. One recurrence was noted in a patient who
      refused surgery, which was recommended because of indeterminate margins. Twenty
      two patients (37 percent) underwent colectomy. Indications included Haggitt Level
      3 or 4 invasion (19), inadequate margins (7), patient preference (1), and poor
      differentiation (1). Residual disease was found in colectomy specimens of three
      patients (14 percent). There were no cancer-related deaths in either treatment
      group. Life table analysis demonstrated a five-year survival of 82 percent for
      the colectomy group and 95 percent for the polypectomy group (P = 0.15).
      CONCLUSION: Treatment of patients with malignant polyps must be individualized
      based on evolving criteria. Patients in whom polypectomy margins are inadequate
      should undergo colectomy. With appropriate selection criteria, patients selected
      for colectomy had a five-year survival rate similar to the rate of those treated
      by polypectomy alone.

PMID- 9269810
TI  - What is the risk factor for metachronous colorectal carcinoma?
AB  - PURPOSE: The purpose of this study was to determine the risk factors for
      developing metachronous colorectal carcinoma and to determine an adequate
      postoperative colonoscopic surveillance. METHODS: Two hundred eighty-four
      patients, examined by routine colonoscopy after resection for colorectal
      carcinoma, were reviewed. Clinical and pathologic factors were assessed by
      multiple logistic regression analysis. RESULTS: One hundred eighty-three patients
      with synchronous adenoma or carcinoma at the initial operation had a
      significantly higher incidence of both metachronous adenoma and carcinoma than
      the 101 patients without a synchronous lesion. Other clinical factors including
      age, gender, tumor stage, tumor site, and tumor grade were not significant for an
      increased incidence of metachronous carcinoma. The presence of synchronous
      lesions proved to be the only risk factor (relative risk, 3.293; P = 0.0155) for
      developing metachronous carcinoma. Metachronous carcinoma was detected in 30
      patients (10.6 percent) and completely removed from all patients. Mucosal
      carcinoma was found in 25 patients (8.8 percent) and invasive carcinoma in 5
      patients (1.8 percent). All five invasive carcinomas were detected in
      asymptomatic patients having synchronous lesion. Four patients required a second
      operation for metachronous carcinoma more than 13 months following the first.
      CONCLUSION: The risk factor for developing metachronous carcinoma is the presence
      of synchronous adenoma or carcinoma at the initial operation. To detect
      metachronous carcinoma at a curable stage, annual colonoscopic surveillance
      should be performed for high-risk patients.

PMID- 9269811
TI  - Operative factors affecting tumor cell distribution following laparoscopic
      colectomy in a porcine model.
AB  - BACKGROUND: An increased risk of laparoscopic port wound tumor implantation in
      the presence of overt or covert abdominal malignancy has been identified.
      PURPOSE: A porcine laparoscopic colectomy model has been used to quantify the
      influence surgical practices may have on tumor cell implantation. METHODS: 51Cr
      labeled, fixed HeLa cells were injected intraperitoneally before surgery. Tumor
      cell contamination of instruments, ports, security threads, and excised wound
      margins was assessed by gamma counting. RESULTS: Greatest contamination occurred
      in ports used by the operating surgeon under pneumoperitoneum (64 percent of all
      port wound tumor cells) and mechanical elevation (76 percent). Gasless surgery in
      patients in the head-down position increased the rostral accumulation of tumor
      cells in the abdomen and right upper quadrant port wound by 330 and 176 percent,
      respectively. Under pneumoperitoneum, port movement was the major contributor to
      port leakage and wound contamination (21 percent of total recovered wound tumor
      cells per port). Tumor cells were not carried in aerosol form. Instrument passage
      and the withdrawal of security threads through the abdominal wall increased port
      wound contamination 430 and 263 percent, respectively, over pneumoperitoneum
      control ports. Preoperative lavage reduced by 61 percent, but did not eliminate,
      wound contamination. CONCLUSION: This porcine model may be used to evaluate
      surgical factors for the impact on port wound contamination.

PMID- 9269812
TI  - Adhesive function of carcinoembryonic antigen in the liver metastasis of KM-12c
      colon carcinoma cell line.
AB  - PURPOSE: Both experimental and clinical results reveal that carcinoembryonic
      antigen (CEA) seems to mediate some important role in the liver metastasis of
      colorectal carcinoma cells. The intent of this study was to verify whether
      adhesive function of CEA might affect liver metastasis in the CEA-expressing
      colon carcinoma cell line, KM-12c. METHODS: The hepatic binding of
      [125I]iododeoxyuridine KM-12c cells was measured with or without intravenous CEA
      pretreatment in four nude mice each. Then, 2 x 10(6) cells of KM-12c were
      injected into the splenic subcapsule of 57 CEA-pretreated nude mice. KM-12c cells
      were prepared in phosphate-buffered saline (control, 27 mice) or anti-CEA
      monoclonal antibody, T84.66 (30 mice). All mice were killed at the end of the
      eighth week after implant, and tumor nodules were confirmed histologically.
      RESULTS: Marginal differences of hepatic sequestration were found between the CEA
      pretreated mice and the control group. Splenic tumor occurred in 75 percent
      (18/24) of the control group and in 40 percent (10/25) of the T84.66-pretreated
      group (P = 0.0107). Forty-two percent (10/24) incurred liver metastasis in the
      control group, whereas 20 percent (5/25) did so in the T84.66-pretreated group.
      The number of splenic tumor cells was significantly related to the number and
      volume of liver metastasis (P = 0.0065). CONCLUSIONS: CEA enhanced liver
      metastasis predominantly by successful primary tumor implant, whereas primary
      hepatic entrapment also supported it to some extent in a weakly metastatic colon
      carcinoma cell line, KM-12c. Tumor cell aggregates seem to be mediated by
      homophilic binding of CEA molecules, and it is an important mechanism to yield
      liver metastasis.

PMID- 9269813
TI  - Postoperative perineal hernia.
AB  - PURPOSE: Perineal hernia is an uncommon complication following abdominoperineal
      resection. The aim of the study was to evaluate the predisposing factors and the
      optimum method of repair. METHODS: A retrospective review of patients with
      postoperative perineal hernia at the Massachusetts General Hospital between 1963
      and 1995 was performed. RESULTS: Twenty-one patients with perineal hernias were
      found. The original perineal operations were as follows: abdominoperineal
      resection in 13 patients, pelvic exenteration in 5 patients, cystourethrectomy in
      2 patients, and perineal resection of the rectal stump in 1 patient. The
      incidence of symptomatic perineal hernia following abdominoperineal resection was
      estimated to be 0.62 percent. A total of 69 percent of patients had the original
      perineal wound left partially open, and in 10 percent it was left completely
      open. The peritoneal defect was not closed in 53 percent of patients, and only 21
      percent had closure of the levator defect. Of the 19 patients who had hernia
      repair, 13 were repaired transperineally and 3 transabdominally and 3 required a
      combined abdominoperineal approach. The repair methods were as follows: simple
      closure of the pelvic defect (10 patients), mesh closure (5 patients), gluteus
      flap (1 patient), and retroflexion of the uterus (2 patients) or bladder (1
      patient). Four patients had postoperative complications (mostly wound
      infections), and the recurrence rate was 16 percent. There was no difference in
      length of hospitalization among transperineal, transabdominal, and combined
      approaches. CONCLUSIONS: Primary closure of the perineal wound, with careful
      avoidance of wound infection is the most important consideration for avoiding a
      perineal hernia. Repair via the perineum with simple closure of the defect or a
      mesh is successful in most cases.

PMID- 9269815
TI  - Role of matrix metalloproteinases in healing of colonic anastomosis.
AB  - PURPOSE: The aim of this study was to compare the distribution of the matrix
      metalloproteinases (MMPs) during anastomotic healing in a normal colon with that
      in an ischemic colon in a rabbit. This family of enzymes degrades all components
      of connective tissue and has been implicated as a cause of anastomotic
      dehiscence. METHODS: A left-sided anastomosis was formed in the distal colon of
      one group of rabbits, and in the other group, 9 cm of distal colon was made
      ischemic before resection and anastomosis 12 hours later. Tissues from the
      anastomosis and sites around the colon were removed at 12 hours, 1 day, and 3
      days after anastomosis and, also, at 7 days in the normal group. Distribution of
      the MMPs and their inhibitor, tissue inhibitor of metalloproteinases (TIMP), was
      localized by indirect immunofluorescence. RESULTS: In rabbits having only an
      anastomosis, the MMPs and TIMP-1 were, at all times, seen solely in the
      anastomotic segment and were strictly confined to the immediate vicinity of the
      suture line. While in rabbits with an ischemic colon before anastomosis, the MMPs
      initially extended several centimeters proximally and distally from the suture
      line. By the third day, however, there were only minor differences between the
      two models. CONCLUSION: Distribution of the MMPs and TIMP-1 in normal healing is
      consistent with a role in the remodeling of colonic anastomosis, but when healing
      of the colon is compromised, these enzymes are more widespread and may contribute
      to anastomotic dehiscence.

PMID- 9269814
TI  - Effect of epidural anesthesia on colorectal anastomosis: a tonometric assessment.
AB  - PURPOSE: Epidural anesthesia is believed to benefit colorectal anastomotic blood
      flow because of the sympathetic blockade it produces. Our purpose is to measure
      with tonometry the effect of epidural anesthesia on colorectal anastomotic
      oxygenation. PATIENTS AND METHODS: Fifteen patients operated on for rectal cancer
      (radical anterior resection) were monitored postoperatively using tonometers
      placed in the stomach (celiac trunk), transverse colon (superior mesenteric
      artery), and the anastomotic area during the operation. An epidural catheter was
      placed at L1-2, and on the first postoperative day, 8 ml of bupivacaine (0.25
      percent) was administered. The anesthetic effect extended up to T-4. Intramucosal
      pH (pHi) at the three locations was measured before, during, and after the
      epidural blockade. RESULTS: Gastric and transverse colon pHi increased during the
      epidural blockade from 7.35 +/- 0.01 to 7.41 +/- 0.01 and from 7.34 +/- 0.02 to
      7.40 +/- 0.02, respectively. The anastomotic pHi decreased from 7.3 +/- 0.02 to
      7.24 +/- 0.03 under the epidural and increased up to 7.34 +/- 0.02 after
      withdrawal of the effect on the following day. All pHi variations were
      statistically significant (P < 0.05, paired Student's t-test and Wilcoxon's
      test), because it was the comparison between gastric and transverse colon pHi
      with the anastomotic pHi during the epidural (P < 0.05, one-way analysis of
      variance and Kruskal-Wallis tests). None of the patients developed anastomotic or
      other complications. CONCLUSIONS: Epidural anesthesia with bupivacaine causes a
      significant decrease in the oxygenation-perfusion state of colorectal anastomosis
      in comparison with the increase in other areas of the digestive tract. Further
      studies need to be done to see if other epidural anesthetic-analgesic protocols
      also worsen colorectal anastomotic blood flow.

PMID- 9269816
TI  - Lymphoma of the pouch after ileal pouch-anal anastomosis: report of a case.
AB  - The most common cause of pouch dysfunction after ileal pouch-anal anastomosis is
      pouchitis. Although low-grade dysplasia in the mucosa of the pouch has been
      recently described in the presence of pouchitis, there has been no report of
      carcinoma arising in the pouch itself. We describe a patient who developed a
      large-cell lymphoma of the ileal pouch after ileal pouch-anal anastomosis.

PMID- 9269817
TI  - Pneumocystis carinii pneumonia postrestorative proctocolectomy for ulcerative
      colitis: a role for perioperative prophylaxis in the cyclosporine era? Report of
      a case and review of the literature.
AB  - PURPOSE: Medical management of severe ulcerative colitis has used cyclosporine
      with increasing frequency as an adjuvant to systemic steroids and mercaptopurine.
      However, the effects of combined management with cyclosporine and prednisone may
      lead to significant immune compromise and adversely affect operative morbidity in
      the event urgent surgery is required. METHODS: A case is reported of a 43-year
      old white male who presented with severe ulcerative colitis. The patient had been
      initially treated with prednisone and cyclosporine for six weeks before surgical
      intervention. The intractability of his ulcerative colitis caused the patient to
      present to surgery, where he underwent restorative proctocolectomy. RESULTS: On
      initial presentation, the patient manifested systemic signs of severe ulcerative
      colitis with hypoalbuminemia, anemia, and weight loss, despite continuous
      prednisone and cyclosporine management. Before surgical intervention, a chest x
      ray and the patient's respiratory status were normal. A total abdominal colectomy
      with ileal pouch reconstruction and temporary loop ileostomy were performed
      without incident. On the fifth postoperative day, the patient developed
      respiratory failure, which was subsequently diagnosed as Pneumocystis carinii
      pneumonia. Although ventilator support and both aggressive medical and surgical
      management eventually resulted in successful outcome, significant perioperative
      morbidity occurred. CONCLUSIONS: In the era of aggressive medical management for
      ulcerative colitis with both steroids and cyclosporine, the complications of
      immunosuppression may be significant, including opportunistic pneumonia.
      Prophylaxis against P. carinii pneumonia with sulfa antibiotics should be
      considered, especially in patients for whom proctocolectomy is a potential end
      point.

PMID- 9269819
TI  - Pursestring skin closure after stoma reversal.
AB  - A simple, inexpensive, reliable, and cosmetically attractive method of stoma
      closure is presented.

PMID- 9269818
TI  - Adjuvant therapy for colorectal cancer: present and future perspectives.
AB  - In recent years, adjuvant therapy for colorectal cancer has advanced
      considerably. This article reviews these advances and provides an update of the
      most recent and ongoing trials. In 1990, adjuvant therapy became the "standard of
      care" for patients with Stage III colon cancer (Dukes C) in the United States.
      Recent clinical trial data indicate that adjuvant treatment may also be effective
      in patients with Stage II (Dukes B2) colon cancer. The combination of 5
      fluorouracil plus leucovorin may slightly improve survival (5-10 percent)
      compared with the standard 5-fluorouracil plus levamisole combination. The three
      drug regimen (5-fluorouracil plus levamisole plus leucovorin) is more toxic, with
      no superior effect on survival. Intraportal chemotherapy, although it may
      significantly improve patient survival, does not decrease the frequency of liver
      metastases. However, it is still a promising form of adjuvant therapy owing to
      its short treatment period and relatively equivalent effects in survival compared
      with that of systemic therapy. For patients with Stage II or Stage III rectal
      cancer, postoperative systemic 5-fluorouracil plus radiation therapy plus
      protracted venous 5-fluorouracil infusion is the most effective postoperative
      adjuvant regimen. However, results from several studies show that preoperative
      radiation alone or chemoradiation for advanced local rectal cancers might also be
      effective while also improving resectability, decreasing morbidity, and
      increasing the chance that a sphincter-sparing procedure may be performed. The
      role of leucovorin in rectal cancer remains to be determined. Immune therapies
      with agents such as interferon-alpha-2a, monoclonal antibody 17-1A, and
      autologous tumor vaccines are being assessed and could further improve survival.

PMID- 9269820
TI  - Influence of botulinum toxin injections on the sphincteric compound muscle action
      potential of the external anal sphincter.

PMID- 9269822
TI  - Chromosomal and DNA ploidy characterization of salivary gland neoplasms by
      combined FISH and flow cytometry.
AB  - Concurrent DNA ploidy by flow cytometry and interphase FISH analysis of
      chromosomes 6 through 12, 17, 18, X, and Y were prospectively performed on 22
      salivary gland neoplasms (four benign and 18 malignant) to investigate the
      diagnostic and biological implications of their alterations in these neoplasms.
      Our results show that benign neoplasms lack DNA aneuploidy and numerical
      chromosomal abnormalities. Low-grade malignant neoplasms, except for two lesions,
      manifested small chromosomal gains and losses and were generally DNA diploid or
      near-diploid aneuploid, whereas all high-grade tumors showed marked polysomy and
      were DNA aneuploid. Marked intratumoral and intertumoral chromosomal
      heterogeneity also were noted in and between individual tumors. Although polysomy
      was the main finding in DNA aneuploid lesions, monosomy was more noted in DNA
      diploid neoplasms and was restricted to chromosomes 8, 11, and 17. Significant
      correlation between the DNA index, chromosomal aneusomy, histological grade, and
      tumor stage was noted. Our study indicates that (1) benign salivary gland
      neoplasms lack gross DNA content and numerical chromosomal abnormalities, (2)
      clonal chromosomal alterations are manifested in most DNA diploid and all DNA
      aneuploid malignant tumors, (3) chromosomal gain is the most common alteration;
      chromosomal loss is less frequent and restricted to certain chromosomes, and (4)
      DNA aneuploidy and chromosomal aneusomy characterize tumors with aggressive
      features.

PMID- 9269821
TI  - Classification of ductal carcinoma in situ: striving for clinical relevance in
      the era of breast conserving therapy.

PMID- 9269823
TI  - Ubiquitin immunostaining and inclusion body myositis: study of 30 patients with
      inclusion body myositis.
AB  - Distinction of inclusion body myositis (IBM) from other forms of inflammatory
      myopathy is significant from prognostic and therapeutic standpoints. This study
      retrospectively examines ubiquitin expression by paraffin immunohistochemistry in
      muscle biopsy material from 30 patients with IBM. Patients included 19 men and 11
      women (ages 29 to 80 years; mean, 64 years). All biopsies were characterized by
      endomysial chronic inflammation, muscle fiber degeneration and regeneration,
      rimmed vacuoles, and angular atrophic esterase-positive muscle fibers. Ragged red
      fibers were identified in biopsies of five patients and a partial cytochrome C
      oxidase deficiency by enzyme histochemistry in biopsies of 10 patients. Evidence
      of intranuclear or cytoplasmic tubulofilamentous structures confirming a
      diagnosis of IBM was observed in all 30 cases. Paracrystalline mitochondrial
      inclusions were noted in five patients. Discrete myocyte intranuclear ubiquitin
      positive inclusions were noted in 14 patients (47%). Discrete intracytoplasmic
      ubiquitin-positive inclusions were noted in 24 (80%) patients. Positive staining
      of rimmed vacuoles by ubiquitin was observed in 25 (83%) patients. Diffuse
      staining of scattered muscle fibers was observed in 21 (70%) patients. In a
      control group including patients with polymyositis (n = 3), dermatomyositis (n =
      3), necrotizing vasculitis (n = 1), and granulomatous myositis (n = 1), discrete
      intranuclear or cytoplasmic ubiquitin-positive inclusions were not observed.
      Rimmed vacuoles were not seen either by light microscopy or ubiquitin
      immunostaining in any of the eight cases. Occasional myofibers from all eight
      cases showed diffuse, positive muscle fiber staining. Although not present in all
      cases, evidence of ubiquitin-positive myocytic intranuclear or cytoplasmic
      inclusions or positive-staining rimmed vacuoles in the setting of an inflammatory
      myopathy may be suggestive of a diagnosis of inclusion body myositis. Use of
      ubiquitin immunohistochemistry may be useful in cases in which frozen tissue or
      tissue processed for electron microscopy is not available, and IBM is suspected.
      Light or electron microscopic evidence of mitochondrial abnormalities were noted
      in a significant subset of patients (13 of 30; 43%) of patients with IBM.

PMID- 9269824
TI  - Loss of RB and MTS1/CDKN2 (p16) expression in human sarcomas.
AB  - The product of the MTS1/CDKN2 gene (p16) and the retinoblastoma protein (pRB)
      inhibit cell cycle progression at the late G1 checkpoint. The absence of
      functional p16 or pRB has been identified in a variety of human tumors but has
      not been well studied in mesenchymal neoplasia. Using an immunohistochemical
      approach, the authors identified abnormal expression of either p16 or RB in 16
      and 14 of 59 sarcomas, respectively, for an overall abnormality rate of 51%.
      Specific rates of abnormality varied by histological subtype, with
      leiomyosarcomas most commonly affected by loss of either tumor-suppressor gene
      product. There was no significant correlation between p16 or RB expression and
      overall grade, mitotic grade, or tumor progression for sarcomas. In contrast, no
      fibromatoses and other spindle cell neoplasms of low malignant potential
      displayed abnormal p16 expression, and only 4 of 23 cases showed loss of pRB
      expression. These data show that aberrant expression of p16/pRB is one of the
      most common molecular derangements in sarcomagenesis.

PMID- 9269825
TI  - Human papillomavirus findings in relation to cervical intraepithelial neoplasia
      grade: a study on 476 Stockholm women, using PCR for detection and typing of HPV.
AB  - Among human papillomavirus (HPV) types found in humans, there is a strong
      association between HPV 16, 18, 31, and 33, and cervical cancer. The relationship
      between various grades of dysplasia and HPV type is less clear. To elucidate this
      point, the authors tested 476 cytological and histological samples from cervix
      with polymerase chain reaction (PCR) for HPV using consensus primer My 09-11 and
      type-specific primers. All cases were divided into groups on the basis of
      cytology: "normal cases" (ie, women with other disease than cervical
      intraepithelial neoplasia [CIN]), and CIN I, II, and III. Out of the "normal
      cases," in which women with a previous history of condyloma and dysplasia were
      included, 69% had HPV with type 6 as the most common one. Of all CIN I cases, 71%
      were HPV positive, and HPV type 6 and 16 were equally common. In CIN II cases,
      HPV 16 was the most common type, whereas HPV 6 accounted for only 7.5% of cases
      in this group as single virus type. HPV 16 was also the most common type in the
      CIN III group, followed by type 33. Double and even multiple infections occurred
      in all groups.

PMID- 9269826
TI  - The clinicopathological characteristics of gonadotroph cell adenoma: a study of
      118 cases.
AB  - Gonadotroph cell adenoma was the most common pituitary adenoma, constituting 35%
      of the pituitary adenomas in our series of 339 patients with surgically removed
      pituitary adenomas from June 1987 to December 1995. The average age of these
      patients was 53 years, with a male predominance (1.5:1). The most common
      neurological symptoms were visual symptoms and headache. Amenorrhea and
      galactorrhea were recorded in 41% and 14%, respectively, of the female patients
      of reproductive age. Oncocytic change of varying degrees was seen in 69% of the
      tumors, and the average age of these patients (56 years) was older than those who
      had no such change (47 years) (P < .005). Five types of gonadotroph cell adenomas
      were recognized; they were tumors that contained (1) betaFSH, betaLH, and
      alphaSU, (2) betaFSH and betaLH, (3) betaFSH and alphaSU, (4) betaFSH, and (5)
      alphaSU. The immunostaining of betaFSH-containing cells was usually diffuse,
      whereas staining of betaLH- or alphaSU-containing cells was usually focal. Double
      immunostaining showed the immunoreactive cells containing one or any combination
      of the gonadotropin subunits. Increases in serum gonadotropin levels were only
      seen in 35% of the patients with gonadotroph cell adenoma. There was no
      correlation between serum hormonal levels and immunostaining results. Of the 33
      recurrent cases, significant decrease or total absence of immunoreactivity of one
      or more hormone subunits in subsequent biopsy specimens were seen in three cases.

PMID- 9269827
TI  - Cysteine protease CPP32, but not Ich1-L, is expressed in germinal center B cells
      and their neoplastic counterparts.
AB  - Ich-1/Nedd2 and CPP32/YAMA are cysteine proteases related to interleukin 1-beta
      converting enzyme (ICE), which act as apoptosis effectors. Both molecules are
      expressed in T- and B-cell lines. The authors investigated their in vivo cellular
      distribution in normal and neoplastic human lymphoid tissues. Sixty-eight
      representative non-Hodgkin's lymphomas (NHL) and Hodgkin's disease (HD) samples,
      normal lymphoid organs, and nonlymphoid tumors were analyzed by
      immunohistochemistry (IHC). CPP32 expression in benign tissues was restricted to
      germinal center B cells, plasma cells, and a few interfollicular immunoblasts.
      All follicular NHLs and most diffuse large cell NHLs were CPP32 positive. Among T
      cell NHLs, CPP32 expression was mainly observed in anaplastic large cell NHLs,
      whereas the other subtypes were less frequently positive. In contrast, lymphoid
      organs displayed only weak Ich1-L expression, located in sinusal histiocytes and
      thymic epithelial cells. Lymphomas were Ich1-L negative, except for T-cell-rich B
      cell NHLs, and about half of the HD samples, in which Reed-Sternberg cells (RSC)
      were usually Ich1-L positive/CPP32 negative. Extralymphoid Ich1-L reactivity was
      found in particular organs like the kidney and various tumors. Western blot
      analysis confirmed the specificity of immunostaining. Neither CPP32 nor Ich1-L
      expression were correlated with intratumoral DNA fragmentation, as determined by
      the TUNEL assay. Altogether, these results indicate that CPP32 is preferentially
      expressed in germinal centers and thus could be involved in B-cell maturation.
      The differential expression of CPP32 and Ich1-L suggests that cysteine proteases
      differ in substrate specificities and carry out functions unrelated to apoptosis.

PMID- 9269828
TI  - Expression of cadherins in benign, borderline, and malignant ovarian epithelial
      tumors: a clinicopathologic study of 60 cases.
AB  - We have analyzed the expression of E- and N-cadherins in benign, borderline, and
      maligant ovarian tumors, and we have correlated the pattern of cadherin
      expression with the standard clinicopathological parameters. An
      immunohistochemical technique has been applied to formalin-fixed, paraffin
      embedded samples of 20 benign cystic tumors, 20 borderline tumors, and 20
      cancers. Expression of E- and N-cadherins immunostaining were compared with the
      histological type, degree of histological differentiation, International
      Federation of Gynecology and Obstetrics (FIGO) stage, presence of ascites,
      occurrence of recurrence, and survival. E-cadherin was homogeneosuly expressed in
      benign tumors but was heterogeneously expressed or undetectable in most
      borderline and malignant tumors. In contrast, N-cadherin was detected in most
      benign and borderline tumors but was absent or heterogeneous in most carcinomas.
      The difference of expression of E-cadherin and N-cadherin between the three
      groups of ovarian tumors was statistically significant (respectively, P = .03 and
      P < .001). In ovarian carcinoma, patients with negative E-cadherin staining
      present a significantly shorter survival. No correlation was found between
      cadherin expression and clinicopathological parameters in borderline tumors. Our
      results suggest that alterations in E-cadherin and N-cadherin expressions are
      differentially involved in ovarian carcinogenesis and may have diagnostic and
      prognostic values.

PMID- 9269829
TI  - Newly marketed tissue markers for malignant mesothelioma: immunoreactivity of
      rabbit AMAD-2 antiserum compared with monoclonal antibody HBME-1 and a review of
      the literature on so-called antimesothelioma antibodies.
AB  - A complementary DNA (cDNA) library was constructed from a human malignant
      mesothelioma (MM) cell line and a cDNA fragment encoding for a cytoplasmic
      mesothelial protein recognized by the polyclonal antibody AMAD-1 was then cloned
      and expressed in Escherichia coli. The purified recombinant protein was used to
      raise a novel antibody, named AMAD-2, in rabbits. This antibody reacted with
      normal mesothelium and most MM (15 of 17) on paraffin sections and featured a
      cytoplasmic labeling. Conversely, AMAD-2 immunostaining of normal and tumor
      tissues from body sites other than serosal membranes was limited with respect to
      the proportion of positive specimens and usually less conspicuous than in MM.
      AMAD-2 immunoreactivity was subsequently compared with staining for HBME-1,
      another newly marketed antimesothelial monoclonal antibody, concerning the
      ability to distinguish pleural MM from metastatic pleural tumors of epithelial
      type. A granular cytoplasmic immunoreactivity for AMAD-2 was present in 50% or
      more of tumor cells in all 84 MM, regardless of histological type, but also in 3
      (7%) of 42 pleural metastases, albeit only focally. HBME-1 was shown in 63 of 66
      epithelial MM and in the epithelial component of all 8 mixed MM, with a
      prevailingly membranous pattern, usually homogeneous and strong, whereas none of
      the 10 sarcomatous MM was positive. HBME-1 was also expressed in 6 (14%) of 42
      pleural metastases in a cytoplasmic or membranous pattern. Compared with HBME-1,
      AMAD-2 showed a higher degree of specificity and sensitivity for MM. AMAD-2 still
      proved to be superior to HBME-1, also when sarcomatoid MM were excluded from the
      assessment. This finding supports the view that AMAD-2 is an antibody highly,
      although not entirely, specific for the mesothelial lineage, whereas HBME-1 is
      probably a cell marker more closely related to the epithelial differentiation of
      MM. Therefore, AMAD-2 is preferable as a positive tissue marker to be
      incorporated in the optimal immunohistochemical panel for the diagnosis of MM.

PMID- 9269830
TI  - Metastatic adenocarcinoma to the brain: an immunohistochemical approach.
AB  - The diagnosis of metastatic adenocarcinoma to the brain of unknown primary is
      problematic, and the role of immunohistochemistry in identifying a source has not
      been fully characterized. Sixty-eight metastatic adenocarcinomas of the brain
      with known primaries were immunostained with antibodies to cytokeratin 7 (CK7),
      cytokeratin 20 (CK20), CAM 5.2, wide-spectrum keratin (WSK), gross cystic disease
      fluid protein-15 (GCDFP-15), glial fibrillary acidic protein (GFAP), estrogen
      receptor (ER), and progesterone receptor (PR). True positive staining was defined
      as CK7 in lung or breast; CK20 in gastrointestinal; and GCDFP-15, ER, and PR in
      breast carcinomas. CK7 immunoreactivity was present in all 27 lung carcinomas and
      14 of 15 breast carcinomas with a sensitivity of 98% and specificity of 78%. CK20
      stained 15 of 16 GI carcinomas with a sensitivity and specificity of 94%. None of
      the cytokeratins stained surrounding brain tissue. GCDFP-15, ER, and PR had
      sensitivities of 33%, 33%, and 87%, with specificities of 92%, 84%, and 28%,
      respectively. PR often stained nuclei of normal brain tissue and was accentuated
      in areas of necrosis or cautery artifact. CK7 and CK20 are highly sensitive and
      specific in patients with metastatic adenocarcinoma to the brain of unknown
      primary. GCDFP-15 and ER are relatively specific, but insensitive markers, and PR
      is nonspecific and difficult to interpret.

PMID- 9269831
TI  - Decreased expression of the cystic fibrosis transmembrane conductance regulator
      protein in remodeled airway epithelium from lung transplanted patients.
AB  - The absence or mislocalization of cystic fibrosis transmembrane conductance
      regulator (CFTR) is regarded as being specific for cystic fibrosis (CF). In
      principle, the supply of a non-CF lung transplant to a CF patient should bring up
      normal CFTR expression in the lower airways. Immunolocalization of CFTR and of
      epithelial differentiation markers (ie, cytokeratins 13, 14, and 18, and
      desmoplakins 1 and 2) was carried out on 21 mucosal biopsies from the upper lobe
      of grafts in non-CF (n = 12) and CF patients (n = 9) retrieved between days 23
      and 1,608 after lung transplantation. Biopsy specimens from seven non-CF and four
      CF patients presented either a pseudostratified respiratory epithelium or slight
      basal cell hyperplasia. CFTR was distributed at the apical membrane of the
      ciliated cells. In remodeled epithelia with basal cell hyperplasia or squamous
      metaplasia, CFTR was either weakly expressed in the cytoplasm of the superficial
      epithelial cells or was undetectable. The extent of epithelium remodeling was
      significantly correlated with an impairment of lung function. The results suggest
      that posttransplant airway epithelium dedifferentiation of the graft leads to the
      loss of properly targeted CFTR irrespective of the underlying disease of the
      recipient.

PMID- 9269832
TI  - Hepatic stellate cells and intralobular innervation in human liver cirrhosis.
AB  - In normal and cirrhotic human liver tissues, we examined immunolocalization of
      alpha-smooth muscle actin (alpha-SMA), endothelin-1 receptor (ET-1R), and S-100
      protein, with special emphasis on the intralobular spaces, using
      immunohistochemical methods. The ratio of the number of hepatic stellate cells
      (HSCs) with closely apposing nerve endings to the total number of HSCs in normal
      livers was compared with that in cirrhotic livers by electron microscopy.
      Immunolocalization of alpha-SMA and ET-1R was obviously recognized along the
      sinusoidal walls in cirrhotic liver and was significantly increased in cirrhotic
      liver compared with that in normal liver. Immunoreactive products for these
      substances were mainly localized in HSCs. However, immunolocalization of S-100
      protein in intralobular spaces was markedly decreased in cirrhotic liver compared
      with that in normal liver. Nerve fibers were ultrastructurally hardly visible in
      intralobular spaces of cirrhotic livers. The ratio of the number of HSCs with
      closely apposing nerve endings to the total number of HSCs was significantly
      reduced in cirrhotic liver compared with that in normal liver. These results
      indicate that in liver cirrhosis, alpha-SMA-positive HSCs may play an important
      role in hepatic sinusoidal microcirculation through vasoactive agents such as ET
      1 rather than through intralobular innervation.

PMID- 9269833
TI  - Mucin carbohydrate antigens (T, Tn, and sialyl-Tn) in human ovarian carcinomas:
      relationship with histopathology and prognosis.
AB  - Altered glycosylation of mucins leading to the expression of T, Tn, and sialyl-Tn
      antigens has been shown in ovarian carcinoma, but its relationship with prognosis
      is still unclear. We investigated immunohistochemically the expression of these
      antigens in 38 (17 serous and 21 mucinous) ovarian carcinomas to assess their
      potential prognostic value as compared with stage of disease, histopathology of
      tumors, and survival time of patients. Eight benign ovarian tumors (four serous
      and four mucinous), and four normal ovarian tissues also were studied. Of the 38
      carcinomas, 25 (66%) expressed T, 27 (71%) expressed Tn, and 33 (87%) expressed
      sialyl-Tn antigens. Most cases (83%) expressed two or all of the three types of
      antigens simultaneously. Normal ovarian epithelia showed no staining for these
      antigens, and benign ovarian tumors were either negative or occasionally
      expressed weak staining in less than 25% of epithelial cell areas. Statistical
      analyses showed strong associations between Tn and sialyl-Tn antigen expressions
      and disease stage as well as histological grade. In 19 ovarian carcinoma patients
      with available survival data, the overall survival times of patients with high Tn
      or sialyl-Tn antigen expression were significantly worse than those of the
      patients with negative and low expression (P < .05 and P < .01). In multivariate
      stepwise regression analysis, disease stage (P = .000) and Tn antigen expression
      (P = .02) were found to be significant independent parameters associated with the
      overall survival time. These findings suggest that, with exception of T antigen
      expression, the expression of Tn and sialyl-Tn antigens in ovarian carcinomas may
      provide additional prognostic information on patient outcome.

PMID- 9269834
TI  - Ductal carcinoma in situ of the breast: reproducibility of histological subtype
      analysis.
AB  - Historically, two major strata of ductal carcinoma in situ (DCIS) have been
      linked to outcome, the presence or absence of comedo type and size. Our initial
      approach in classification was dichotomous, often favoring the comedo type with
      most worrisome implications to foster agreement in diagnosis. We have now tested
      guidelines that foster agreement in the modified Lagios three-tiered system.
      Sixteen cases of DCIS were selected, reflecting a spectrum of histological
      subtypes, with specific inclusion of cases in which consensus in classification
      using a dichotomous (comedo/noncomedo) scheme would be difficult. Six independent
      observers reviewed a minimum of five color 35-mm slides from each case at two
      separate occasions. The aim was to subclassify each case based on architectural
      pattern, nuclear grade, and presence or absence of tumor necrosis (Modified
      Lagios Classification, Lagios et al, Cancer 1989). After initial review,
      emphasizing placement of each case into a high- or low-grade category, there was
      disagreement in seven cases (44%), confirming our aim to choose cases with
      uncertain cues for classification. Agreement was achieved in 94% of cases by
      allowing re-review with emphasis on inclusion of an intermediate-grade category.
      Our study also suggests that pure micropapillary DCIS and apocrine DCIS warrant
      independent classification as "special type" DCIS. Our small pilot study suggests
      that, with adherence to specific criteria, most DCIS cases can be easily and
      consistently classified into the following five categories: (1) high grade, (2)
      intermediate grade, (3) low grade, (4) pure or predominantly micropapillary, and
      (5) pure apocrine. Our six observers independently reached a final concordance of
      94% despite selection of cases in which consensus in a dichotomous classification
      was difficult. This was achieved predominantly by accepting an intermediate
      category of DCIS with intermediate nuclear features and limited necrosis.
      Confirmation of the applicability of the Modified Lagios Classification awaits
      completion of a much larger multi-institutional study in which statistical
      significance and interobserver variation can be better defined.

PMID- 9269835
TI  - Relationship of a new histological categorization of ductal carcinoma in situ of
      the breast with size and the immunohistochemical expression of p53, c-erb B2, bcl
      2, and ki-67.
AB  - Ductal carcinoma in situ (DCIS) represents a heterogeneous group of diseases.
      There is no generally accepted classification for the different cytological and
      architectural types of DCIS. A recent study (Scott et al, 1995) indicates that
      over 90% of DCIS can be easily classified into the following five categories:
      high grade (HG), intermediate grade (IG), low grade (LG), pure micropapillary
      (M), and pure apocrine (A). The aim of this study was to determine if there is a
      relationship between lesion size and the immunohistochemical expression of p53, c
      erb B2, bcl-2, and ki67 with this reproducible categorization of DCIS. Seventy
      cases of DCIS diagnosed between 1984 and 1995 were obtained from the Departments
      of Pathology at two teaching hospitals in London, Ontario. The original sections
      were reviewed, classified according to Scott et al (1995), and representative
      sections were cut for immunohistochemical (IHC) studies. IHC stains were scored
      using a previously described semiquantitative scoring system (Allred et al,
      1993). Size was taken from the gross measurement if the lesion was palpable or
      recorded as the largest dimension, as measured on the histological slide, for
      nonpalpable cases. Of the 70 DCIS cases, 17 (24.3%) were HG, 23 (32.9%) were IG,
      21 (30%) were LG, seven (10%) were pure micropapillary cases, and two (2.9%) were
      pure apocrine DCIS. The mean size of the DCIS for each subcategory was
      statistically significantly different (P = .008). In particular, the
      micropapillary DCIS cases were largest (mean size, 17 mm). The mean
      immunohistochemical scores for c-erb B2 for each category were also statistically
      different (P = .007), whereas the mean scores for p53 and ki67 for each category
      trended toward significance (P = .073, P = .062, respectively). There were no
      significant differences between bcl-2 mean scores and each subcategory. Size of
      DCIS and c-erb B2 positivity are known to be associated with more aggressive
      clinical behavior and more advanced histologic features, respectively. Because
      this combined histological cytological classification system is predictive of
      size and c-erb B2 positivity, our results support the clinical relevance of this
      classification system.

PMID- 9269836
TI  - Systemic lupus erythematosus-associated lymphoproliferative disorder: report of a
      case and discussion in light of the literature.
AB  - A case of autoimmune disease-associated lymphadenopathy (ADAL) with histological,
      immunophenotypic, Epstein-Barr virus (EBV) in situ hybridization, and genotypic
      analyses is presented. The patient had a well-documented history of systemic
      lupus erythematosus (SLE) and was found at autopsy to have massive
      lymphadenopathy, thymic enlargement, pulmonary nodules, and polyclonal serum
      dysproteinemia. Histological examination revealed a polymorphous lymphoid
      infiltrate containing many plasma cells, rare immunoblasts, and a pronounced
      arborizing vasculature. No foci of necrosis were found and there was no evidence
      of lymphocyte depletion. The plasma cells were immunophenotypically polyclonal
      and no EBV mRNA (EBER-1) or gene rearrangements were identified. The unusual
      gross features, which resembled a malignant lymphoproliferative process, as well
      as the unusual histological features make this case a notable addition to the
      spectrum of atypical lymphoproliferative disorders associated with an autoimmune
      disorder. We conclude that although reminiscent of angioimmunoblastic
      lymphadenopathy with dysproteinemia (AILD), this case lacks the diagnostic
      features of AILD, and is, perhaps, best classified as an autoimmune disease
      associated lymphadenopathy (ADAL).

PMID- 9269838
TI  - Polymerase chain reaction-based detection of B-cell clonality in the fine needle
      aspiration biopsy of a thyroid mucosa-associated lymphoid tissue (MALT) lymphoma.
AB  - Although it is possible to diagnose primary high-grade thyroid lymphoma from a
      fine needle aspiration (FNA) biopsy, the distinction of low-grade B-cell lymphoma
      of mucosa-associated lymphoid tissue (MALT) from lymphocytic thyroiditis is
      sometimes problematic. Definitive diagnosis of lymphoma on cytologic specimens
      may be facilitated by the documentation of a clonal lymphoid proliferation within
      the specimen by flow cytometric immunophenotyping or immunocytochemistry.
      Recently, molecular techniques have also been developed to detect clonal lymphoid
      proliferation based on immunoglobulin (Ig) or T-cell receptor gene rearrangement.
      We have used a polymerase chain reaction (PCR)-based assay for Ig heavy chain
      gene arrangement to identify a clonal population of lymphocytes within the
      thyroid FNA specimen from a low-grade thyroid MALT lymphoma. Using this assay, we
      identified no distinct clonal population in five cytologic specimens of
      lymphocytic thyroiditis. Therefore, this PCR-based clonality assay represents a
      potentially useful adjunct to the cytologic diagnosis of thyroid lymphoma.

PMID- 9269837
TI  - Epithelioid angiosarcoma of bone.
AB  - Angiosarcoma of bone is a rare, high-grade sarcoma of vascular origin. This
      article describes an epithelioid angiosarcoma in the humerus of a 48-year-old
      man. A multilocular osteolytic lesion with undefined margins and destroyed
      cortical and medullary bone, associated with a large soft tissue mass was
      demonstrated radiologically in the proximal metaphysis of the right humerus. The
      tumor, resected by amputation, was composed mostly of proliferating malignant
      cells with an epithelioid morphology. It had a predominantly sheet-like growth
      pattern, and an occasional pseudoglandular or alveolar arrangement, mimicking an
      adenocarcinoma. The dilated anastomotic vascular spaces lined by epithelioid
      endothelial cells and the intracytoplasmic lumina/vacuoles that sometimes
      contained erythrocytes suggested focal endothelial differentiation. On
      immunohistochemical investigation, many neoplastic cells expressed cytokeratin
      and endothelial markers: factor-VIII related antigen, CD31, and UEA-I. The
      ultrastructure of the tumor was consistent with that of an angiosarcoma. Our
      patient died of disease shortly after the diagnosis, implying an aggressive
      clinical course. Awareness of the existence of skeletal epithelioid angiosarcoma,
      combined with the identification of intracytoplasmic lumina, or at least small
      vasoformative foci, and immunohistochemical positivity for endothelial markers
      provide the best guide for distinguishing this tumor from metastatic carcinomas.

PMID- 9269839
TI  - Metastatic malignant mesothelioma presenting as colonic polyps.
AB  - A 66-year-old male engineer diagnosed with malignant pleural mesothelioma 4 years
      previously had thoracotomy, radiotherapy, and chemotherapy. He was followed
      regularly with chest computed tomography (CT) scan and had been asymptomatic.
      During one of his physical examinations, routine sigmoidoscopy showed incidental
      colonic polyps which were biopsied. Subsequently, recurrence of pleural
      mesothelioma and peritoneal involvement by mesothelioma was documented. Two of
      the polyps showed metastatic malignant mesothelioma in the lamina propia which
      strongly resembled adenocarcinoma histologically causing difficulty in making
      definitive diagnosis. Review of the literature disclosed no previously documented
      similar occurrence. This case shows the importance of clinical history and
      ancillary laboratory procedures such as immunohistochemistry and electron
      microscopy to avoid diagnostic pitfalls.

PMID- 9269840
TI  - Should subjective diagnoses conform to generally accepted definitions of disease
      entities and syndromes?

PMID- 9269841
TI  - Evaluation of medical education.

PMID- 9269850
TI  - Metabolic and mitotic changes associated with the fetal alcohol syndrome.
AB  - In the USA, fetal alcohol syndrome (FAS) is the leading known cause of mental
      retardation. FAS is estimated to affect 4000 infants yearly in the USA with an
      additional 7000 children suffering various forms of fetal alcohol effects in the
      absence of the full syndrome. A comparable incidence would be expected in other
      industrialized countries, but essentially no data are available from either
      developing or third world countries. An understanding of the biochemical causes
      of FAS has been slow to develop, but progress has been made toward a molecular
      causation theory of FAS. This paper summarizes much of the current work as to the
      effects of fetal ethanol exposure on mitotic and metabolic parameters as well as
      ethanol's effect on the cellular signalling pathways thought to regulate these
      processes. Based upon these studies, it is apparent that exposure of embryonic
      tissue to ethanol results in decreased growth and that alcohol adversely affects
      a multitude of cellular functions critical for the growth of the developing
      organism, including inhibition of protein and DNA synthesis. In addition, ethanol
      alters the uptake of critical nutrients such as glucose and amino acids and
      causes changes in several kinase-mediated signal transduction pathways that
      regulate these biochemical processes.

PMID- 9269851
TI  - Women, alcohol and the menstrual cycle.
AB  - This review presents evidence which implicates a role for menstrual cycle phase
      in the response of pre-menopausal women to moderate alcohol intake. It is
      concluded that the majority of published studies have suffered from poor
      methodological design and have employed inadequate means of cycle phase
      identification. Contradictory and ill-founded findings have been reported. The
      best evidence to date suggests that women eliminate alcohol more rapidly during
      the mid-luteal phase of the cycle. This finding needs to be substantiated by
      further studies.

PMID- 9269852
TI  - ESBRA-Nordmann 1996 Award Lecture: ethanol drinking behaviour in Sardinian
      alcohol-preferring rats.
AB  - Sardinian alcohol-preferring (sP) rats have been selectively bred for high
      ethanol preference and consumption over 16 years and 39 generations. The present
      paper briefly reviews some recent studies from this laboratory characterizing
      ethanol drinking behaviour in this rat line. Under the two-bottle regimen of free
      choice between 10% (v/v) ethanol and water, sP rats consume daily >4 g of
      ethanol/kg and avoid water almost completely. Relevant features of ethanol
      drinking behaviour in sP rats are: (a) attainment of high ethanol intake from the
      first day of exposure to ethanol, suggestive of an immediate disclosure and
      acquisition of ethanol reinforcement; (b) titration of daily ethanol intake in
      distinct binges during the nocturnal phase of the light/dark cycle, indicative of
      their ability to regularize both ethanol dose and administration time; (c)
      achievement of pharmacologically relevant blood ethanol levels at each drinking
      episode; (d) substitution of the calories provided by ethanol for a part of those
      taken from food; (e) maintenance of constant ethanol intake (in g/kg/day) in the
      presence of ethanol concentrations varying from 7 to 30% (v/v). These results
      suggest that voluntary ethanol intake in sP rats is sustained by the search for
      specific pharmacological effects of ethanol. Anxiolysis is likely to be one of
      these effects; indeed, voluntarily consumed ethanol reversed the innate, high
      levels of anxiety in sP rats. These results portray sP rats as a valid model for
      investigating the association between ethanol drinking and anxiety. Finally, the
      breeding programme as well as results of neurochemical studies are also
      described.

PMID- 9269853
TI  - Effects of 5-HT3 receptor agonists on voluntary ethanol intake in rats maintained
      on a limited access procedure.
AB  - Recent evidence from a variety of laboratory studies suggests that the central
      effects of ethanol (EtOH) are mediated by serotonin 5-HT3 receptors. Notably,
      EtOH is able to potentiate 5-HT action on 5-HT3 ionophore, and 5-HT3 antagonists
      are known to reduce certain effects of EtOH. In the present study, we evaluated
      the effects of two agonists of 5-HT3 receptors, 2-methyl-5-HT (2-Me-5-HT) and m
      chlorophenylbiguanide (m-CPBG) that were microinjected i.c.v. and into the
      nucleus accumbens (NAC) on EtOH intake in Wistar rats with high EtOH preference.
      2-Me-5-HT given i.c.v. (1 and 10 microg per rat) and into the NAC (bilaterally 1
      and 10 microg per site) significantly reduced EtOH intake in the limited access
      paradigm (2h session). On the other hand m-CPBG was inactive after intra-NAC
      administration. It is concluded that central 5-HT3 receptors are involved in the
      regulation of EtOH consumption.

PMID- 9269854
TI  - Effects of lifelong ethanol consumption on rat locus coeruleus.
AB  - The effects of lifelong ethanol consumption and ageing on the morphology of locus
      coeruleus (LC) were studied in alcohol-preferring AA (Alko Alcohol) rats of both
      sexes. Ethanol (12% v/v) was the only available liquid for the ethanol-consuming
      rats from 3 months up to 24 months of age. Young (3-month-old) and old (24-month
      old) control groups were included in the measurements. The LC morphometry was
      performed by an unbiased disector method. In the old control rats, the total
      neuron number, neuronal density and the volume of the LC proper did not differ
      from the young controls. In the ethanol-exposed rats, the total neuron number of
      the LC was decreased by 30% and the LC neuronal density by 22%, compared to the
      age-matched controls. No gender difference was found in the vulnerability of LC
      neurons to ethanol-induced degeneration. The results suggest a remarkable
      sensitivity of the LC neurons to the ethanol-induced degeneration in both male
      and female rats. The possible mechanisms and functional implications of this
      neuronal loss are discussed.

PMID- 9269856
TI  - Alcohol consumption and gustatory hedonic profiles in Wistar-Kyoto hyper- and
      normoactive rat strains.
AB  - The purpose of the present study was to compare the consummatory behaviour of
      rats of the Wistar Kyoto Hyperactive (WKHA) strain, selected for their
      hyperactivity in a novel environment, with the normoactive Wistar-Kyoto (WKY)
      rats in three choice tasks: between water and increasing concentrations of
      saccharin, between water and increasing concentrations of quinine, and between
      water and a 10% (v/v) ethanol solution. The results of the present study show
      that: (1) WKHA rats exhibited a significantly higher acceptance of a 10% (v/v)
      alcohol solution than the normoactive control WKY rats when alcohol solution was
      the only available fluid; (2) WKHA rats also showed significantly larger alcohol
      intakes during the 15 days of choice between water and alcohol (WKY: 0.39 +/-
      0.05; WKHA: 1.72 +/- 0.26 g/kg/day); (3) as frequently cited in the literature
      for other strains, the higher level of alcohol ingestion of WKHA rats was
      associated with a higher preference for saccharin; (4) no strain differences were
      observed in the water-quinine choice test. The discussion is mainly centred on
      the small alcohol consumption of the two strains, since the intake of WKHA rats
      is in the normal range for consumption of outbred strains, while the amount of
      alcohol consumption of WKY rats is very low and in the range of alcohol intake of
      non-preferring rat strains. It is concluded that the difference in alcohol
      consumption is mainly due to the low intake of the WKY rats and it is suggested
      that their different level of consumption might result from the particular
      behavioural profile of these rats.

PMID- 9269855
TI  - The GABAergic system of the dentate gyrus after withdrawal from chronic alcohol
      consumption: effects of intracerebral grafting and putative neuroprotective
      agents.
AB  - We have demonstrated that, in the rat hippocampal formation, withdrawal from
      chronic alcohol consumption aggravates the ethanol-induced loss of pyramidal
      neurons and dentate granule cells. We have also shown that intracerebral grafting
      and piracetam could have a protective effect in these conditions. In this study
      we utilized immunocytochemical methods to investigate whether gamma-aminobutyric
      acid (GABA)ergic dentate gyrus cells, which are known to be inhibitory, were also
      affected by withdrawal from alcohol and, if so, whether putative neuroprotective
      agents could ameliorate the alterations found. Rats were alcohol-fed for 6 months
      and further divided into several groups: (1) alcohol-fed for an extra 6 months;
      (2) withdrawn from alcohol for 6 months; (3) withdrawn and grafted with newborn
      rat hippocampal tissue; (4) withdrawn and orally treated with piracetam for 6
      months; (5) withdrawn and treated systemically with monosialoganglioside GM1 for
      6 months; (6) withdrawn and treated with the vehicle used to dissolve the GM1.
      Control animals were pair-fed. All animals were killed 12 months after the
      beginning of the experiment and processed for GABA immunocytochemistry. GABA
      immunoreactive (IR) neurons in the dentate gyrus were quantified and we found
      that alcohol-fed animals had a significant reduction in the numerical profile
      density of GABA-IR neurons in the dentate gyrus as a whole and in the hilus and
      in the granular layer of the suprapyramidal limb. Withdrawal from alcohol
      aggravated the GABAergic neuronal loss. Of the treatments used, only piracetam
      had a striking beneficial effect. Data gathered from the present work and from
      our previous studies indicate that the neuronal loss following chronic alcohol
      consumption and withdrawal affects both excitatory and inhibitory neurons in the
      dentate gyrus and that piracetam may have a useful protective role in this
      condition.

PMID- 9269857
TI  - Thiamine deficiency in head injury: a missed insult?
AB  - Practice regarding the use of thiamine in head-injured patients at risk of
      Wernicke-Korsakoff syndrome in Scottish neurosurgical units was surveyed by
      questionnaire and revealed no clear policy. A 2 year retrospective study of 218
      admissions to one of these units of patients who had taken alcohol shortly before
      sustaining head injury is also described. The minority (20.6%) of the total had
      been given thiamine, with just over half (56.1%) of those categorized as
      alcoholic receiving this treatment. Additional carbohydrate loads, in the form of
      i.v. dextrose or parenteral nutrition, had been given to 44.5% of patients and
      only 28.9% of this group had also been given thiamine. The dose and duration of
      thiamine given was inadequate in most cases. It is suggested that failure to
      ensure that head injury patients at risk of Wernicke-Korsakoff syndrome receive
      appropriate thiamine prophylaxis represents a missed and treatable additional
      insult to the damaged brain.

PMID- 9269858
TI  - 'Overshoot' of ethanol in the blood after drinking on an empty stomach.
AB  - The time required for ethanol to distribute between the systemic circulation and
      the rest of the body water results in an 'overshoot' of the blood-alcohol
      concentration (BAC) during the first 30 min after intravenous infusion. To
      investigate whether a similar distribution phenomenon occurs when ethanol is
      given by the oral route, we compared BACs after intravenous infusion and oral
      intake under strictly controlled conditions by giving a 0.4 g/kg dose of ethanol
      over 15 min to six fasting female volunteers. The results show an 'overshoot' in
      three volunteers who had the shortest time to BACmax, which indicates rapid
      absorption, and the time-course was similar to the distribution phase seen during
      the intravenous experiments. We conclude that BAC is sometimes higher than
      expected shortly after alcohol has been ingested rapidly. This finding can
      probably be explained by the fact that ethanol is distributed more slowly
      throughout the total body water than it is absorbed from the gut.

PMID- 9269859
TI  - Comparison of two commercial test kits for quantification of serum carbohydrate
      deficient transferrin.
AB  - Serum levels of carbohydrate-deficient transferrin (CDT) were measured in
      subjects of two independent studies using two different commercial kits. The kits
      measure CDT either as a percentage of total transferrin (AXIS %CDT, AXIS
      Biochemicals AS, Norway), or as the absolute amount (CDTect, Pharmacia, Sweden).
      In a population of males (mean age 41 years) consisting of alcoholics, heavy,
      moderate and non-drinkers, a strong correlation was found between AXIS %CDT and
      CDTect results (r = 0.92, n = 58, P < 0.001). Sensitivity and specificity in
      detecting chronic alcoholic drinking of over 60 g/day were 78 and 94% for the
      AXIS assay, and 83 and 88% for the CDTect assay, respectively. In a population
      from a birth cohort study, consisting of 21-year-old males and females with less
      excessive alcohol consumption, the correlation between AXIS %CDT and CDTect CDT
      was weaker but still statistically significant (r = 0.46, n = 212, P < 0.001). In
      this population, with specificities > 83% in detecting alcohol consumption levels
      of > or = 6 drinks per week, the sensitivities were low with both CDT assays (<
      43% for > or = 6 drinks per week, and < 44% for > or = 16 drinks per week). These
      results suggest that (a) both assays are equally effective in detecting chronic
      drinking over 60 g/day in older alcoholic males, and (b) both assays are
      similarly ineffective in detecting less excessive regular drinking in young males
      and females.

PMID- 9269860
TI  - The significance of coronary death for the excess mortality in alcohol-dependent
      men.
AB  - General and validated cause-specific mortality, especially regarding coronary
      disease, was studied in a population-based cohort of 1049 alcohol-dependent (DSM
      III-R) men, who were discharged from a detoxification ward. The observed and
      expected numbers of deaths were 140 and 23.2, respectively (P < 0.001). The
      estimated risk quotient of death was 6.0 (95% confidence interval 5.1-7.1). The
      concordance between revised and official causes of death was approximately 50%,
      but the resulting variation of risk quotients of cause-specific deaths generally
      remained within the statistical uncertainty. Coronary disease contributed to 19%
      of the total excess mortality in cases with a validated definite death diagnosis.
      The risk of coronary death tended to be augmented during the first 2 years of
      discharge (P = 0.05). Thus, coronary death contributed significantly to the
      excess mortality in alcohol-dependent men, and an increased vulnerability for
      sudden coronary death seemed to persist for a considerable time after discharge
      from detoxification.

PMID- 9269861
TI  - Alcoholism: a long-term follow-up study of participants in an alcohol treatment
      programme.
AB  - This paper reports the results of a long-term follow-up study of 112 alcoholic
      patients admitted to an intensive 1-month residential programme. Outcomes at the
      6-month and 1-year stages were reported in an earlier paper [G. K. Shaw et al.
      (1990) British Journal of Psychiatry 157, 190-196]. The length of the follow-up
      period in this study was an average of 9 years. Eighteen patients had died before
      the long-term follow-up stage, and of the remaining 94 a total of 60 patients
      were followed up. This study shows that major improvements on social,
      psychological and drinking behaviour measures, made at 6 months and 1 year follow
      up, were, on the whole, maintained and there was a progressive improvement on
      most variables at each follow-up stage. Major improvements were achieved by those
      patients whose drinking was categorized as 'abstinent', 'controlled' and
      'improved'. The proportion of patients categorized as 'unchanged' dropped from
      43% at 6 months to 33% at 1 year and to 15% at 9 years. By the 1-year follow-up
      stage, the unchanged group showed deterioration on psychological variables such
      as neuroticism, self-esteem and satisfaction with life situations, continued to
      make use of health service resources, and the high level of alcohol-related
      physical and social complications remained unchanged. This group had similar
      results at long-term follow-up with the exception of neuroticism, which was
      significantly lower in all drinking categories.

PMID- 9269862
TI  - Increased carbohydrate-deficient transferrin during pregnancy and relation to sex
      hormones: %CDT will not yield false positive results.

PMID- 9269863
TI  - The functional role of P-glycoprotein in the blood-brain barrier.

PMID- 9269864
TI  - Pharmaceutical processing with supercritical carbon dioxide.
AB  - Replacement of traditional solvents with "environmentally benign" carbon dioxide
      is receiving increased attention in pharmaceutical processing. Among the reported
      applications, particle formation with dense carbon dioxide and the "clean"
      synthesis of drug compounds using carbon dioxide as a reaction medium hold
      immense potential for large-scale application in the pharmaceutical industry.
      This paper provides an overview of these rapidly emerging technologies along with
      examples of the wide variety of relatively contaminant-free pharmaceutical
      compounds that have been processed via these technologies on a laboratory scale.
      Challenges facing successful implementation in practice include demonstration of
      continuous production and harvesting of particles with desired and reproducible
      product characteristics. Mathematical models aimed at a better fundamental
      understanding of the underlying thermophysical phenomena are essential for
      rational design and scale-up of these technologies.

PMID- 9269865
TI  - A novel biodegradable system based on gelatin nanoparticles and poly(lactic-co
      glycolic acid) microspheres for protein and peptide drug delivery.
AB  - Gelatin nanoparticle-poly(lactic-co-glycolic acid) (PLGA) microsphere composites
      were prepared by encapsulating protein-loaded gelatin nanoparticles in PLGA
      microspheres. This encapsulation was conducted by using a phase separation method
      and a solvent extraction method. The average diameter of the gelatin nanoparticle
      PLGA microsphere composites is between 160 and 175 microm. Protein loading
      efficiency is 93.2% for the nanoparticle-microsphere composite prepared by the
      phase separation method, while it is 31.31% for the composite prepared by the
      solvent extraction method. Protein release experiments indicate that this new
      composite system possesses sustained release characteristics. This system also
      demonstrates the capability of preventing the denaturation of protein drugs.

PMID- 9269866
TI  - Percutaneous absorption of salicylic acid after repeated (14-day) in vivo
      administration to normal, acnegenic or aged human skin.
AB  - The objective of the present work was to determine the relative bioavailability
      of salicylic acid (SA) after repeated (14-day) topical application to subjects
      who presented normal, acnegenic, or photodamaged facial skin. To emulate exposure
      characteristics likely to be encountered by subjects in these two subpopulations,
      individuals presenting facial acne were treated with 2% SA in a hydroalcoholic
      vehicle, and volunteers with aged or photodamaged skin received a comparable
      topical dose of SA in a cream (moisturizer-like) vehicle. Plasma concentration
      time profiles and cumulative urinary excretion of SA were measured after the last
      dose in subjects who had received 15 consecutive daily topical applications of 27
      mg of SA or oral doses of 81 mg of acetylsalicylic acid (ASA). The rate and
      extent of percutaneous absorption of SA were not affected by facial skin
      condition. Faster rates of absorption (Cmax) were obtained with a hydroalcoholic
      compared with a cream vehicle. Systemic SA exposures were at least five-fold
      higher with oral ASA than topical SA. Based on systemic salicylate concentrations
      resulting from ingestion of 81 mg of ASA, these results support that patients
      without gross skin disorders are at minimal risk of adverse systemic effects from
      routine use of topical products containing 2% SA.

PMID- 9269867
TI  - Examination of the compaction properties of a 1:1 acetaminophen:microcrystalline
      cellulose mixture using precompression and main compression.
AB  - The compaction properties of a 1:1 acetaminophen and microcrystalline cellulose
      (MCC) mixture have been studied using a compaction simulator to make tablets by
      single compression and by a combination of precompression and main compression.
      The tensile strengths of the tablets and the energies involved in the
      compressions were determined. The tensile strengths of the tablets increased with
      increases in single compression pressure from 80 to 400 MPa and as the total
      applied pressure increased from 80 MPa up to around 400 MPa when combinations of
      precompression and main compression pressures were used. The tablet porosity
      decreased with increase in main compression pressure while the tablet tensile
      strengths increased. At minimum tablet porosity, further increase in main
      compression pressure could no longer result in increase in tablet strengths.
      Tablets compressed with combinations of precompression and main compression were
      stronger (2.15 +/- 0.02 to 3.99 +/- 0.1 MPa) than those produced with single
      compression (0.73 +/- 0.01 to 3.09 +/- 0.05 MPa). The total gross energies of
      compression increased with an increase in pressure of both the precompression and
      main compression. The elastic energies during main compression increased with an
      increase in precompression pressure as the tablet exhibited greater elastic
      deformation and reduced plasticity on second compression. The increase in elastic
      energies during main compression may also be because elastic energy is
      recoverable and is independent of precompression. As the precompression pressure
      increased, the minimum tablet porosity was attained; hence, the plastic energy
      during main compression became smaller while the elastic energy increased. Thus,
      a combination of low precompression and main compression pressures of 160/80 MPa
      or 80/160 MPa are more advantageous in the tableting of the 1:1 acetaminophen:MCC
      than a high single compression pressure of 320 or 400 MPa.

PMID- 9269868
TI  - Factors affecting the in vitro release of recombinant human interferon-gamma
      (rhIFN-gamma) from PLGA microspheres.
AB  - A long-acting depot formulation of recombinant human interferon-gamma (rhIFN
      gamma) was achieved by microencapsulation of rhIFN-gamma in polylactic-coglycolic
      acid (PLGA) microspheres by a water-in-oil-in-water technique. The release of
      protein was assessed with different release devices and buffer systems. The
      quality of the released protein was quantitated by sodium dodecyl sulfate-size
      exclusion chromatography, ELISA, and bioactivity assays. The microencapsulation
      process resulted in an encapsulation efficiency of 100% and the initial release
      of bioactive, native protein with no subsequent release. Further investigation
      suggested that the protein did not bind to the PLGA, but a constant and small
      amount of protein adsorbed to the filter device used for the release studies. The
      composition of the release media (pH, buffer species, salt concentration, ionic
      strength, and type and concentration of surfactants) had a profound effect on the
      in vitro release rate. The effect was mainly due to the differential solubility,
      stability, and aggregation of rhIFN-gamma in the various systems for protein
      inside the microspheres or released into the bulk solution. The quality of the
      protein released from the microspheres was also affected by the buffer media upon
      storage at 5 degrees C, which, in turn, affected the quantification of released
      protein. The bicinchoninic acid method typically used to quantitate protein
      release underestimated protein release because of aggregation. Protein released
      after several days was less active than the starting material and had lost
      activity as a result of the inherent instability of rhIFN-gamma at 37 degrees C.
      The release device, buffer species, pH, and excipients must be assessed in
      release studies of proteins from polymer matrices because the protein stability
      and release is dependent on these variables. These studies also indicated that
      rhIFN-gamma was encapsulated and released from PLGA in a bioactive form, but its
      stability at 37 degrees C, which was greatly affected by the release conditions,
      limits the duration of release of native, bioactive protein to 7 days or less.

PMID- 9269869
TI  - Identification of the glucuronides of the hydroxylated metabolites of the
      antimalarial arteether in rat plasma and urine by thermospray high-performance
      liquid chromatography/mass spectrometry.
AB  - A method was developed to quantitate the glucuronide conjugates (phase II
      metabolites, log P = 0.6-1.8) of the phase I hydroxylated metabolites (log P =
      2.6-2.7) of beta-arteether (2) (log P = approximately 4.0) in rat plasma and
      urine. The biological fluids were extracted with a C-18 solid-phase cartridge,
      then subjected to analysis by thermospray high-performance liquid
      chromatography/mass spectroscopy with a C-18 reversed-phase analytical column in
      the selected ion monitoring mode. The detection limits for these glucuronide
      conjugates in plasma and urine ranged from 25 to 60 ng/mL, and the detection
      limits were appropriate for the biological activity of these glucuronide
      conjugates in plasma. Following intravenous administration of arteether (11.6
      mg/kg), the formation of these glucuronide conjugates in rat urine was undetected
      (below detection limit) over 24 h. However, in rat plasma, formation of 9alpha
      hydroxyarteether glucuronide (13; 255 ng/mL, IC50 = 6560 ng/mL, log P = 0.93) was
      noted at 15 min post-injection. Although several of the glucuronide metabolites
      of arteether retained sufficient in vitro antimalarial activity to be potentially
      useful antimalarial agents if administered as prodrugs, the levels of the
      glucuronides formed from arteether were too low to contribute to the antimalarial
      activity observed for the parent compound.

PMID- 9269870
TI  - Preparation of liposomes encapsulating water-soluble compounds using
      supercritical carbon dioxide.
AB  - In this paper the development of a new preparation method of liposomes containing
      a water soluble marker (fluorescein isothiocyanate-dextran (FITC-dextran) or zinc
      phthalocyanine tetrasulfonic acid (TSZnPc) using supercritical carbon dioxide
      (called "the supercritical liposome method") is described. The apparatus used
      consisted of two main parts: the high-pressure part, in which the lipid
      components 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) and cholesterol (Chol)
      (7:3 molar ratio) were dissolved under pressure in supercritical carbon dioxide,
      and a low-pressure part, in which the homogeneous supercritical solution is
      expanded and simultaneously mixed with the aqueous phase to yield liposomes
      encapsulating the water soluble marker. Addition of 7% absolute ethanol to carbon
      dioxide at 25 MPa and 60 degrees C and the use of a high-pressure recycling
      system during 30 min form the homogeneous solution with high reproducibility of
      both lipid components and resulted in an equal expansion profile (recovery after
      expansion versus time) of POPC and Chol. Incubation of the lipid components
      during 60 min at the above mentioned conditions generated only 3% degradation.
      The average size of the liposomes was about 200 nm and could not be influenced by
      the experimental conditions used. Optimal values for encapsulated volume (1.25
      L/mol) and efficiency (20%) of the liposomes were obtained using statistical
      experimental design by using the water soluble marker TSZnPc and an encapsulation
      capillary with 5.0 cm length and 0.5 mm inner diameter. The total amount of
      ethanol used to obtain an encapsulation efficiency of 20% was 15-fold reduced
      compared to the ethanol injection method of Batzri and Korn (Biochim. Biophys.
      Acta 1973, 298, 1015-1019).

PMID- 9269871
TI  - Dissolution mechanism of diclofenac sodium from wax matrix granules.
AB  - Dissolution behavior of diclofenac sodium (DS) from wax matrix granules (WMGs)
      prepared using a twin-screw compounding extruder is closely related to swelling
      ability and solubility of the rate-controlling agent employed. A swellable and
      soluble (hydroxypropyl)-cellulose (HPC-SL) generates both an expansion of pores
      inside WMGs and a structural change observed as cracking on the surface of WMGs.
      These changes are confirmed by mercury porosimetry. Release of DS was increased
      with an increase in the amount of HPC-SL in WMGs, but only 35% of DS was released
      from WMGs containing 73% (w/w) NaCl at the 24 h point of the dissolution.
      Further, no cracking was observed on the surface of NaCl-containing WMGs. A
      linear relationship between mean dissolution time (MDT) of DS for WMGs containing
      different types of HPC (HPC-SL, -M, and -H) and swelling abilities suggests that
      release of DS could be directly controlled by swelling of HPCs. In addition to
      this result, an application of the exponential model (Mt/M infinity = kt(n))
      introduced by Ritger and Peppas (J. Controlled Release 1987, 5, 23-36) to DS
      release indicates that case II release plays a critical role in HPC-SL-containing
      WMGs and Fickian release is predominant in NaCl-containing WMGs since the values
      of n of WMGs containing 73% (w/w) NaCl and 40% (w/w) HPC-SL are 0.41 and 0.71,
      respectively. These results suggest that proper selection of rate-controlling
      agents based on their physicochemical properties (such as swelling ability and
      solubility) is important in designing WMGs with desired dissolution profiles.

PMID- 9269872
TI  - Mechanism of alpha-cyclodextrin-induced hemolysis. 1. The two-step extraction of
      phosphatidylinositol from the membrane.
AB  - It has been suggested that the interaction of cyclodextrins with the lipid
      components of the erythrocyte membranes is the determining factor in the
      hemolysis induced by these cyclic oligosaccharides. In the case of alpha
      cyclodextrin (cyclomaltohexose), phospholipids have been identified as the cell
      target. In our study, evidence for the interaction between alpha-cyclodextrin and
      different phospholipids has been obtained using synthetic membranes. Since
      phosphatidylinositol (PI) showed the strongest affinity for alpha-cyclodextrin,
      it has been selected to investigate the respective contributions of the polar
      head group and the aliphatic chains to the association process using 31P, 2H, and
      1H NMR spectroscopy. In this work, we describe the two-step extraction of PI from
      the membrane following its association with alphaCD: a cyclodextrin molecule is
      first attracted to the membrane surface by electrostatic remote interactions and
      associates with the lipid head group. Then the whole PI molecule is extracted,
      and inclusion of its unsaturated sn-2 acyl chain into another alphaCD molecule
      occurs in the bulk.

PMID- 9269873
TI  - Effects of intravenous infusion of lidocaine on its pharmacokinetics in conscious
      instrumented dogs.
AB  - In this study, potential alterations in hepatic blood flow, plasma protein
      binding, hepatic tissue binding, and enzyme activities induced by LD iv infusion
      of lidocaine (LD) were evaluated using a chronically instrumented dog model. Four
      conscious female mongrel dogs (19.0-23.5 kg) were each given, on days 1 and 10, a
      5-min infusion of a mixture of unlabeled LD at approximately 2 mg/kg and 14C
      labeled LD at approximately 25 microCi and, on day 8, a 12-h constant rate iv
      infusion of LD (approximately 76 microg/kg/min). During LD infusion, there was a
      11-79% increase in total hepatic blood flow, mainly due to a 1.6-9.2-fold
      increase in hepatic arterial flow. Despite similar blood clearance (27.5 +/- 6.0
      mL/min/kg vs 27.5 +/- 3.5 mL/min/kg), volume of distribution at steady state
      (1.38 +/- 0.08 L/kg vs 1.36 +/- 0.17 L/kg), and free fraction values of LD
      between days 1 and 10 (p > 0.05), intrinsic clearance values were consistently
      reduced (1224 +/- 859 mL/ min/kg vs 285 +/- 104 mL/min/kg; p = 0.034).
      Furthermore, hepatic tissue uptake of LD and/or its metabolites was less on day
      10 than on day 1 (39.7 +/- 14.5 micromol vs 30.1 +/- 15.1 micromol; p = 0.072).
      The extent of N-dealkylation of LD to MEGX was unaltered, whereas sequential
      biotransformation of MEGX was impaired. Hence, these findings suggested that LD
      infusion led to a reduction of hepatic intrinsic clearance, although the change
      was not significant enough to alter its conventional kinetic parameters.

PMID- 9269874
TI  - Contrasting nutrient effects on the plasma levels of an amino acid-like
      antiepileptic agent from jejunal administration in dogs.
AB  - The absorption of gabapentin was investigated by monitoring drug plasma levels as
      a function of time following midjejunal administration in mongrel dogs. From
      previous work, dose-dependent absorption had been postulated to be a consequence
      of carrier-mediated transport and a paracellular pathway had been postulated to
      contribute to the passive absorption component in mammalian small intestine. The
      potential for amino acid inhibition of the carrier-mediated absorption component
      was investigated by drug coinfusion with leucine and phenylalanine. The potential
      for monosaccharide-enhanced increases in drug absorption was studied by drug
      coinfusion with D-glucose and 3-O-methylglucose. While lower drug plasma levels
      were observed with amino acid coinfusion versus controls in each of the dogs
      studied, mean area under the plasma level time curves (AUC) were not
      statistically significantly different (p < or = 0.07). Monosaccharide coinfusion
      significantly increased gabapentin AUC over control studies (p < or = 0.014) and
      over coinfusion with L-system amino acids (p < or = 0.0025). Implications for the
      mechanisms of intestinal absorption of this amino acid-like antiepileptic drug in
      this canine model are discussed.

PMID- 9269875
TI  - Factors that influence microdialysis recovery. Comparison of experimental and
      theoretical microdialysis recoveries in rat liver.
AB  - Inhibition of metabolic processes was used to assess the possible change in the
      recovery of material from a microdialysis probe implanted in vivo in rat liver.
      Phenacetin and antipyrine were perfused through a microdialysis probe implanted
      in the liver. Inhibition of phenacetin and antipyrine metabolism was achieved
      through an iv bolus dose of the cytochrome P450 suicide substrate 1
      aminobenzotriazole (1-ABT). 1-ABT inhibited phenacetin clearance by 90%, thus
      also inhibiting metabolism by 90%. There was no statistical difference in the
      recovery of phenacetin and antipyrine across the microdialysis membrane in the
      liver between the control and metabolically inhibited animals. Partial
      differential equations were developed that describe the transport of analyte from
      the microdialysis probe and solved by an implicit finite-difference method to aid
      in the understanding of the above-mentioned microdialysis experiments.
      Predictions of microdialysis recovery obtained from the numerical model are
      compared with those found experimentally. The model could predict trends in the
      data, but not the actual experimental values. This suggests that predictions from
      this microdialysis model are essentially heuristic and as presently formulated
      can be used only to show mechanisms that affect recovery, but they cannot be used
      to accurately predict recovery. Prediction of actual recovery requires knowledge
      of the values of the parameters that describe chemical properties such as the in
      vivo diffusion coefficient, metabolism rate constant, and capillary exchange rate
      constant. For microdialysis experiments performed in the liver, capillary
      exchange and the rate of liver blood flow appear to be the dominant processes
      that facilitate net transport from a microdialysis probe rather than metabolic
      processes. These results indicate that microdialysis recoveries measured after
      inhibition of a concentration-dependent kinetic process via pharmacological
      challenge will change only when the kinetic process that is being challenged is
      large compared to the contribution of all concentration-dependent kinetic
      processes, including other metabolism routes, capillary exchange, or uptake that
      remove the analyte from the tissue space. It is concluded that the microdialysis
      recovery of a substance from the liver is not generally affected by liver
      metabolism.

PMID- 9269876
TI  - Propofol pharmacokinetics and pharmacodynamics assessed from a cremophor EL
      formulation.

PMID- 9269877
TI  - Determination of the optical purity of ibuprofen using X-ray powder diffraction.

PMID- 9269878
TI  - Metabolic deesterification of tazarotene in human blood and rat and human liver
      microsomes.
AB  - Tazarotene is a novel acetylenic retinoid for the treatment of psoriasis and
      acne. We examined (1) the hydrolysis of tazarotene in blood from Japanese
      American and Caucasian subjects, (2) the esterases responsible for this
      hydrolysis in human blood, and (3) tazarotene hydrolysis in rat and human liver
      microsomes. Tazarotene hydrolysis and enzyme inhibition were assessed by
      monitoring the disappearance of tazarotene and the appearance of its primary
      metabolite tazarotenic acid by HPLC. In blood, tazarotene was converted mainly to
      tazarotenic acid via first-order kinetics, and there was no statistically
      significant difference in the hydrolytic (metabolic) rate of tazarotene in
      uninhibited Japanese-American and Caucasian blood. Physostigmine (a
      cholinesterase inhibitor), bis(p-nitrophenyl) phosphate (a carboxylesterase
      inhibitor), and EDTA (an aromatic esterase inhibitor) did not significantly
      affect tazarotene hydrolysis in blood. Paraoxon, an inhibitor of all serine
      esterases including cholinesterase and carboxylesterase, decreased the hydrolysis
      of tazarotene to tazarotenic acid by 95% in both blood and liver microsomes. In
      conclusion, blood and liver esterases play a significant role in the hydrolysis
      of tazarotene to tazarotenic acid, and paraoxon-inhibitable forms of esterases
      are involved in this hydrolysis in humans.

PMID- 9269879
TI  - Intranasal absorption of oxymorphone.
AB  - The nasal bioavailability of oxymorphone HCI was determined. Rats were surgically
      prepared to isolate the nasal cavity, into which a solution of oxymorphone was
      administered. A reference group of rats was administered oxymorphone HCl
      intravenously. Plasma oxymorphone concentrations were determined by HPLC. Nasal
      absorption was rapid, nasal bioavailability was 43%, and the iv and nasal
      elimination profiles were similar. Oxymorphone HCI appears to have the
      solubility, potency, and absorption properties required for efficient nasal
      delivery, which is an alternative to injections.

PMID- 9269880
TI  - Effects of decreasing sedentary behaviors on activity choice in obese children.
AB  - In this study, methods of decreasing highly preferred sedentary behaviors were
      compared and the consequent effects on activity choice were examined. Following
      free choice of sedentary and physical activities, 34 obese children either were
      positively reinforced for decreases in high-preference sedentary activity, were
      punished for high-preference sedentary activity, had access to high-preference
      sedentary activity restricted, or had no contingencies on activity (control
      group). Children randomized to reinforcement and punishment were more physically
      active on intervention days than the control group. Liking for targeted sedentary
      activity decreased in the reinforcement group, but increased in the restriction
      and control groups. Results suggest that reinforcing decreases in high-preference
      sedentary activity can increase physical activity and decrease liking for
      targeted sedentary activities.

PMID- 9269881
TI  - Nonpsychiatric medical comorbidity, health perceptions, and treatment outcome in
      patients with panic disorder.
AB  - Panic disorder is frequently complicated by high rates of co-occurring
      nonpsychiatric medical conditions. The present study examined the relationship
      between medical morbidity, perceived physical health, and treatment outcome in
      panic disorder. Patients meeting the American Psychiatric Association's
      Diagnostic and Statistical Manual of mental disorders (1994) criteria for panic
      disorder (N = 71) completed 12 sessions of cognitive-behavioral treatment and
      were assessed at posttreatment and 6-month follow-up. Medical comorbidity and
      perceived health were both found to be related to end-state functioning. Medical
      comorbidity did not uniquely predict outcome beyond its shared variance with
      perceived health. At posttreatment, 71% of patients who perceived their physical
      health as good met recovery criteria compared with only 35% of those who
      perceived their health as poor. At follow-up, 67% of those who perceived their
      physical health as good met composite recovery criteria compared with only 33% of
      those with perceived poor health. These findings offer preliminary support for
      the impact of physical health, both actual and perceived, on treatment outcome of
      patients with panic disorder.

PMID- 9269882
TI  - Silent versus symptomatic myocardial ischemia: the role of psychological and
      medical factors.
AB  - This study examined the relationship of psychological, cardiac, and general
      medical history factors to asymptomatic (silent) versus symptomatic myocardial
      ischemia among 102 patients who underwent treadmill exercise testing and had
      perfusion imaging indicative of ischemia. During exercise, 68 patients exhibited
      silent ischemia, and 34 experienced chest pain. Patients with silent ischemia
      rated higher than symptomatic patients on anger control, externally oriented
      thinking, and somatosensory amplification, but did not differ on depression or
      global alexithymia. Anger control and externally oriented thinking remained
      independent correlates in multivariate analysis, controlling for demographic and
      cardiac factors. Groups did not differ on general medical or cardiac variables.
      Thus, this study suggests that affective and cognitive factors, but not
      biomedical factors, are associated with silent, as opposed to symptomatic,
      ischemia during exercise testing.

PMID- 9269883
TI  - The relationship between socioeconomic status, hostility, and blood pressure
      reactions to mental stress in men: data from the Whitehall II study.
AB  - This study investigated the relationship among blood pressure reactions to mental
      stress, cynical hostility, and socioeconomic status (SES) in 1,091 male public
      servants. Occupational grade served to index SES and cynical hostility was
      assessed using the Cook-Medley scale. (Cook & Medley, 1954). The magnitude of
      systolic, but not diastolic, blood pressure change scores to stress was
      positively associated with occupational grade: the higher the grade, the greater
      the reactions. Mental stress task performance also varied with occupational grade
      but was unrelated to reactivity. Ratings of task difficulty did not vary with
      occupational grade. Cynical hostility was negatively related to occupational
      grade, and, contrary to previous findings, negatively related to systolic blood
      pressure reactivity. Cynical hostility was also negatively related to mental
      stress task performance but unrelated to ratings of task difficulty.

PMID- 9269884
TI  - Self-esteem and the relation between risk behavior and perceptions of
      vulnerability to unplanned pregnancy in college women.
AB  - This article reports 2 studies testing the hypothesis that individuals with high
      self-esteem are more likely than those with low self-esteem to interpret
      information about their personal vulnerability to health risks in a self-serving
      manner. Study 1 used an experimental paradigm to demonstrate that self-esteem
      moderates the influence of review of sexual and contraceptive behavior on college
      women's perceptions of vulnerability to unplanned pregnancy (N = 125). Study 2
      used a longitudinal design to demonstrate that self-esteem also moderates the
      relation between naturally occurring changes in college women's sexual behavior
      and changes in their risk perception (N = 273). Together, these studies provide
      evidence that people with high self-esteem use self-serving cognitive strategies
      to maintain their risk perceptions.

PMID- 9269885
TI  - Survey of pediatric hospitals' preparation programs: evidence of the impact of
      health psychology research.
AB  - A survey of all 123 nonchronic-care pediatric hospitals in the United States
      revealed that 75% of hospitals responding had greatly increased the use of
      effective medical procedure preparation technologies, such as filmed modeling and
      coping skills instruction, in comparison to the last survey. Respondent
      characteristics such as position (e.g., nurse, child life worker, physician),
      degree (e.g., RN, MA, PhD), and length of time in the position failed to predict
      the type of techniques selected, but higher respondent knowledge and more
      psychological sources of preparation information did predict the use of
      preparation techniques used for drawing blood that experts rated as more
      effective. Challenges for more effective dissemination of research in the future
      are considered, as is the need for increased study of research-implementation
      links.

PMID- 9269887
TI  - Assessment of self-efficacy and coping with cancer: development and validation of
      the cancer behavior inventory.
AB  - This article reports the development of a measure of self-efficacy for coping
      with cancer. Items culled from a variety of sources were chosen for inclusion in
      the Cancer Behavior Inventory (CBI) based on the psychometric properties of the
      items and the fit of the items in a factor structure. Factor analysis on a group
      of 502 persons with cancer yielded 6 factors: (a) Maintenance of Activity and
      Independence (alpha = .89), (b) Coping With Treatment-Related Side Effects (alpha
      = .88), (c) Accepting Cancer/Maintaining Positive Attitude (alpha = .87), (d)
      Seeking and Understanding Medical Information (alpha = .88), (e) Affective
      Regulation (alpha = .75), and (f) Seeking Support (alpha = .77). Cronbach's alpha
      for the entire measure was .96, and correlations with other measures supported
      its validity. The CBI may be useful for research and clinical practice.

PMID- 9269886
TI  - Comparability and representativeness of clinical homeless, community homeless,
      and domiciled clinic samples: physical and mental health, substance use, and
      health services utilization.
AB  - Evaluating the representativeness of homeless samples is important for
      generalizing research findings on the homeless and designing interventions
      targeting their health needs. The present study contrasts homeless and domiciled
      free-clinic users (216 homeless [132 men, 84 women], 212 domiciled [102 men, 110
      women]) and 531 community homeless persons (388 men, 143 women) on latent
      variables representing substance use, mental and physical health, appearance,
      life satisfaction, and health services utilization (HSU). Homeless clinic
      patients equalled the community sample in substance abuse and psychological
      problems but exceeded the sample in HSU and cleanliness. Homeless clinic users
      reported more substance abuse, poorer health, greater mental illness and mental
      HSU, less cleanliness, and lower life satisfaction than domiciled patients.
      Relationships among the variables are reported, and implications concerning
      health needs among the homeless are discussed.

PMID- 9269888
TI  - Psychometric properties of the Questionnaire on Stress in Patients with Diabetes-
      Revised (QSD-R).
AB  - This study reports the psychometric properties of a 45-item diabetes-specific
      questionnaire, the Questionnaire on Stress in Patients with Diabetes--Revised
      (QSD-R), a modified and shortened version of the QSD (G. Duran, P. Herschbach, S.
      Waadt, A. Zettler, & F. Strian, 1995). The QSD-R was filled out by 1,930
      individuals with insulin-dependent diabetes mellitus and noninsulin-dependent
      diabetes mellitus. Eight consistent scales were identified (values of Cronbach's
      alpha: .69-.81). The test-retest reliability for the total score after a 5-week
      interval was rtt = .63. The results provide evidence for the reliability and
      validity of this instrument.

PMID- 9269889
TI  - Evaluation of the validity of the condom use self-efficacy scale (CUSES) in young
      men using two behavioral simulations.
AB  - Assessment of behavioral skills remains critical to the evaluation of HIV
      prevention interventions; however, investigators often rely upon participant
      reports of self-efficacy to estimate such skills. We evaluated the relationship
      between self-efficacy beliefs for condom use and behavioral performance. Forty
      three men completed the Condom Use Self-Efficacy Scale (CUSES) and participated
      in 2 behavioral assessments. Regression analyses indicated that the CUSES
      subscales relevant to negotiation of condom use did not account for a significant
      amount of variability in interpersonal skills; similarly, the CUSES subscale
      relevant to technical condom use skill did not account for variability in the
      condom application scores. We caution investigators against the assumption that
      higher self-efficacy reflects behavioral competence for HIV-risk reduction.

PMID- 9269890
TI  - Health locus of control and value for health in smokers and nonsmokers.
AB  - A representative sample of 11,401 persons completed a questionnaire, including
      measures of health locus of control, value for health, and smoking frequency.
      Smokers held stronger internal, chance, and powerful others beliefs than never
      smokers. Ex-smokers had lower scores on internal and chance dimensions and placed
      a higher value on their health than smokers. The interaction between chance
      health locus of control and value for health was a significant predictor of
      smoking status, suggesting that health value may moderate the relationship
      between health locus of control and smoking status. Within smokers, the health
      locus of control dimensions and value for health explained less than 1% of the
      variance in smoking frequency, with only the chance dimension emerging as a
      significant predictor.

PMID- 9269891
TI  - Psychological aspects of organ donation: a critical review and synthesis of
      individual and next-of-kin donation decisions.
AB  - This article presents a critical review of psychological perspectives on organ
      donation. The review considers individual decisions to donate organs posthumously
      and next-of-kin consent decisions. A theoretical analysis of intention to donate
      is presented for both types of donation decisions, and the literature is reviewed
      within the context of the proposed framework. Donation decisions are examined as
      a function of attitude toward donation and the religious, cultural, altruistic,
      normative, and knowledge-based beliefs that comprise the attitude. Consent
      decisions are primarily influenced by prior knowledge of the deceased
      individual's wishes. An alternative conceptual model is offered to explain the
      basis of consent decisions in the absence of this knowledge. Suggestions are
      offered to improve measurement strategy and to guide theoretically based organ
      donation research within selected disciplines of psychology.

PMID- 9269892
TI  - Absence of p53 in a mouse mammary tumor model promotes tumor cell proliferation
      without affecting apoptosis.
AB  - Loss or mutation of p53 may have multiple biological and genetic effects that
      result in accelerated tumor progression. Loss of p53 in some tumors has been
      correlated with a marked decrease in tumor cell apoptosis. p53 loss may also
      accelerate tumor growth through an increase in cell proliferation rates. To
      examine the effects of p53 loss on tumor progression in a controlled experimental
      context, we previously crossed p53-deficient mice to mammary tumor-susceptible
      Wnt-1 transgenic (TG) mice. The resulting female Wnt-1 TG offspring of this cross
      all developed mammary tumors, regardless of p53 status (p53+/+, p53+/-, or p53-/
      ). However, female p53-/- Wnt-1 TG mice developed tumors much sooner than their
      p53+/+ counterparts. In this report, we demonstrate that the average growth rates
      of tumors missing (p53-/-) or losing p53 (p53+/- with loss of heterozygosity) are
      accelerated compared to tumors with both wild-type p53 alleles (p53+/+). This
      accelerated growth rate appears to be due primarily to increases in rates of
      tumor cell proliferation. Tumor cell apoptotic levels were modest and were not
      measurably different in the presence or absence of wild-type p53. These results
      differ substantially from other mouse tumor models in which p53 loss was closely
      correlated with accelerated growth rates through attenuated apoptosis. Thus, the
      mechanisms by which p53 loss influences tumor progression may differ, depending
      on the tissue type and/or the oncogenic pathways involved.

PMID- 9269893
TI  - Stably transfected HC11 cells provide an in vitro and in vivo model system for
      studying Wnt gene function.
AB  - The in vitro and in vivo effects of several Wnt family members have been studied
      using stably transfected HC11 cells, a clonal mammary epithelial cell line
      derived from a midpregnant mouse mammary gland capable of hormone-dependent
      differentiation in vitro. Differential effects of Wnt-1, Wnt-2, and Wnt-7B
      expression were observed both on the morphology of confluent HC11 cells and on
      the pattern of E-cadherin expression. Wnt-7B had no apparent effect on HC11 cell
      morphology or E-cadherin expression, as compared to mock-transfected HC11 cells.
      Injection of stably transfected pools of Wnt-1, Wnt-2, Wnt-7B, and mock
      transfected cells into the cleared fat pad of syngeneic BALB/c mice generated
      reproducible outgrowths after 8 or 12 weeks. Mock-transfected cells produced
      outgrowths that exhibited some morphologically normal ductal and alveolar-like
      structures. However, no morphologically normal structures were observed in the
      fat pads containing Wnt-transfected cells. Instead, these outgrowths were
      characterized by significant fibrosis, epithelial hyperplasia, and multiple sites
      of growth. In contrast to the lack of an observed effect in vitro, palpable
      adenocarcinomas were observed 12 weeks after injection of the Wnt-7B-transfected
      HC11 cells. These tumors contained significant regions of hyperplastic and
      transformed epithelium and lacked the fibrotic phenotype observed in the Wnt-1
      and -2 outgrowths. These results support the hypothesis that different Wnt family
      members may elicit distinct functional effects and reinforce the need to perform
      simultaneous comparisons of Wnt function both in vitro and in vivo. Stably
      transfected HC11 cells provide a useful model system in which to elucidate the
      function of different Wnt family members.

PMID- 9269894
TI  - Differential expression of the regularly spliced wild-type p53 and its COOH
      terminal alternatively spliced form during epidermal differentiation.
AB  - In the present study, we investigated the role of p53 in the differentiation of
      epidermal keratinocyte cells. The interrelationship between p53 expression and
      the various stages of epidermal differentiation and the role of the COOH terminus
      of the p53 molecule in this process were determined by comparing the expression
      of the regularly spliced p53 (RSp53) molecule and that of the COOH-terminal
      alternatively spliced (ASp53) form. p53 mRNA distribution was studied by in situ
      analysis of frozen skin sections and by reverse transcription-PCR analysis of the
      various wild-type p53 forms expressed in neonatal skin cell fractions separated
      by Percoll gradient. p53 protein levels were measured by fluorescence-activated
      cell sorting analysis and immunohistochemistry, using antibodies that recognize
      either the COOH terminus of RSp53 or ASp53. The results show that although less
      mature keratinocyte cells predominantly express the RSp53 form, the more mature
      cells preferentially express the ASp53 form. Therefore, it is possible that the
      two p53 forms are associated with different functions required at the various
      stages of keratinocyte differentiation. The results suggest that the COOH
      terminal domain of the p53 molecule is important for its activity in the process
      of keratinocyte differentiation.

PMID- 9269895
TI  - Characterization of platelet-derived growth factor (PDGF) action on a mouse
      neuroblastoma cell line, NB41, by introduction of an antisense PDGF beta-receptor
      RNA.
AB  - We have shown previously that platelet-derived growth factor (PDGF) has trophic
      effects on dopaminergic neurons in vitro. We now examined a mouse neuroblastoma
      cell line, NB41, for its response to PDGF and studied their phenotypic
      characteristics following introduction of an antisense PDGF beta-receptor RNA.
      NB41 cells produce both PDGF-AA and -BB; however, they carry only PDGF beta
      receptors, responding to BB but not to AA. Culturing the cells with PDGF-BB
      induced mRNA for c-fos and PDGF-beta receptor as well as that of neuron-specific
      enzyme, tyrosine hydroxylase. In contrast, mRNA of chromogranin A, which is
      produced by chromaffin cells, decreased. Introduction of an antisense PDGF beta
      receptor RNA in NB41 cells completely suppressed neurite extension and cell
      growth. We compared the PDGF-beta receptor sense and antisense clones for their
      survival. Following serum withdrawal, NB41 cells showed a DNA ladder, which by an
      addition of the neurotoxin, 6-hydroxy dopamine (6-OHDA), resulted in a further
      enhancement of the DNA ladder. The addition of PDGF-BB prior to 6-OHDA rescued
      cells from undergoing apoptosis, seen as a reduction of the DNA ladder. The
      antisense clone, regardless of the presence of PDGF-BB in the culture, showed a
      pronounced DNA ladder after serum withdrawal, which was further enhanced by the
      addition of 6-OHDA.

PMID- 9269896
TI  - Treatment of U937 cells with bufalin induces the translocation of casein kinase 2
      and modulates the activity of topoisomerase II prior to the induction of
      apoptosis.
AB  - The treatment of human leukemia U937 cells with 10(-8) M bufalin in the absence
      of serum resulted in the immediate translocation of casein kinase 2 (CK 2) from
      the cytoplasm to the nucleus, as determined by confocal laser-scanning
      microscopy. Concomitantly, the activity of topoisomerase (topo) II, as determined
      by monitoring activities specific to this enzyme such as DNA relaxation, DNA
      decatenation, and topo II-mediated DNA cleavage, was enhanced. The activity
      reached a maximum after 3 h and then decreased markedly after treatment with
      bufalin for 9 h. The amount of a complex of CK 2 and topo IIalpha in U937 cells
      was estimated by immunoprecipitation with antibodies raised against subunits of
      CK 2 and against topo IIalpha. The amount increased just after the start of
      treatment with bufalin and reached a maximum at 6 h. The results suggest that the
      topo IIalpha in the complex might have been phosphorylated by the translocated CK
      2 and that the topo activity was stimulated by such phosphorylation. Apoptotic
      U937 cells with fragmented nuclei were observed between 9 and 12 h after the
      start of treatment using 10(-8) M bufalin. Therefore, it appears that the bufalin
      signal was transmitted to the nucleus by the translocation of CK 2, which formed
      a complex with topo IIalpha and modulated the activity of this enzyme, leading to
      the induction of apoptosis.

PMID- 9269897
TI  - Immunohistochemical analysis of the proapoptotic protein Par-4 in normal rat
      tissues.
AB  - Prostate apoptosis response 4 (par-4) is a recently identified gene that encodes
      a transcription factor, Par-4, with a leucine zipper domain. Par-4 protein is
      constitutively expressed in various cell lines and is functionally required but
      not sufficient for apoptosis. Induction of Par-4 in cultured cells is found
      exclusively during apoptosis, and ectopic overexpression of Par-4 enhances the
      potency of apoptotic stimuli. Western or Northern blot analysis on mRNA or
      protein extracts, respectively, from rat organs revealed that the expression of
      Par-4 was ubiquitous and was not restricted to any specific organ(s). To further
      identify specific cell types that expressed Par-4, we performed an
      immunohistochemical analysis of the protein in paraffin-embedded sections of
      various organs from rats. Our findings indicated that consistent with its
      proapoptotic role, Par-4 is expressed in apoptotic granulosa cells of atretic
      ovarian follicles and in terminally differentiated cells, such as the
      cardiomyocytes, cerebellar Purkinje cells, and pyramidal cells of the
      hypothalamus. Moreover, testosterone ablation by castration of rats caused an
      early and transient induction of Par-4 in the ductal cells of the prostate that
      undergo apoptosis. By contrast, in tissues in which the cells could be visually
      differentiated from their mature counterparts, Par-4 expression was lowest in the
      mature cells. This was the case for epithelia of the mammary and the prostate
      gland in which the basal cells maintained higher protein levels of Par-4 than did
      the terminally differentiated ductal cells. Similarly, cells of the stratum
      corneum of the skin and cells on top of the duodenal villi stained less intensely
      for Par-4 as compared to the stem cells in the stratum basale and at the bottom
      of the crypts of Lieberkuhn, respectively. It is possible that Par-4 has to be
      down-regulated for successful differentiation in these tissues. Taken together,
      the widespread expression of Par-4 in various adult cell types underscores the
      physiological importance of the protein. The observation of constitutive Par-4
      expression in the stem cell compartments is inconsistent with the probability of
      apoptosis per se and can be extended to determine whether Par-4 plays a role in
      other cellular processes.

PMID- 9269898
TI  - Cellular ras gene activity is required for full neoplastic transformation by the
      large tumor antigen of SV40.
AB  - To investigate the role of the cellular ras gene product in neoplastic
      transformation by the SV40 large tumor antigen (SVLT), murine C3H10T1/2 cells
      were rendered deficient in Ras activity by transfection with inducible or
      constitutive antisense ras gene constructs or through the introduction of the
      dominant-negative mutant, ras(asn17). Consistent with previous results, SVLT
      induced morphological transformation was unaffected by the down-regulation of c
      ras gene product activity. On the other hand, colony formation in soft agar and
      tumorigenicity in nude mice were drastically reduced in c-Ras-deficient cells. In
      addition, SVLT expression in C3H10T1/2 cells led to increased c-Ras activity, as
      determined by an increase in the Ras-bound GTP/GTP + GDP ratio. These results
      suggest that c-Ras is required for full neoplastic transformation by SVLT.

PMID- 9269899
TI  - Antisense estrogen receptor RNA expression increases epidermal growth factor
      receptor gene expression in breast cancer cells.
AB  - In human breast cancer, progression to a more malignant phenotype is often
      accompanied by decreased expression of estrogen receptor (ER) and increased
      expression of epidermal growth factor receptor (EGFR). Higher levels of this
      receptor tyrosine kinase are found in tumors lacking ER, and a quantitative,
      inverse relationship exists between the level of ER and EGFR mRNA in human breast
      cell lines. Antisense ER (ASER) RNA was used to evaluate the consequence of
      decreased ER expression in breast cancer cells, specifically to determine whether
      ER is involved in the regulation of EGFR gene expression. ER-positive MCF-7 human
      breast cancer cells were transfected with ASER, and clones constitutively
      expressing ASER RNA had decreased ER and up to a 3-fold increase in the
      expression of EGFR mRNA. To confirm that this observation was a direct
      consequence of ASER expression, a metal-inducible ASER expression construct was
      transfected into MCF-7 cells, and transfected clones were isolated and
      characterized. Northern analysis revealed an induction of ASER RNA within 1 h of
      the addition of zinc, which was followed by a 4-fold increase in EGFR mRNA
      levels, maximal at 6-12 h. The basal level of expression of the glucocorticoid
      receptor is also inversely related to that of ER among breast cancer cell lines,
      but neither constitutive nor inducible expression of ASER affected the expression
      of glucocorticoid receptor. These data support the hypothesis that the level of
      expression of ER specifically influences the expression of EGFR in human breast
      cancer cells and provides a potential link between loss of steroid sensitivity
      and the acquisition of autonomous growth.

PMID- 9269900
TI  - Characterization of a nuclear factor that binds juxtaposed with ATF3/Jun on a
      composite response element specifically mediating induced transcription in
      response to an epidermal growth factor/Ras/Raf signaling pathway.
AB  - We have previously identified a 20-bp sequence that mediates induced
      transcription in response to EGF, Ras, and Raf but not after TPA or UV
      stimulation. This composite response element, present in a long terminal repeat
      of a member within the VL30 family of retrotransposons, contains an AP-1-like
      site that cooperates in function with a juxtaposed sequence unrelated to known
      transcription factor-binding sites. Using in vitro translated proteins, we here
      demonstrate that the AP-1-like site preferentially binds ATF3/c-Jun and ATF3/JunD
      heterodimers. Results from a functional analysis indicate that the ATF3/c-Jun
      heterodimer, together with factors interacting with the 3' element, are most
      likely the important mediators of the response because overexpression of JunD,
      alone or in combination with ATF3, abolishes Ras-induced transcription. Partial
      purification by phosphocellulose and DNA-affinity chromatography in combination
      with Southwestern analyses reveals a 52-kDa protein that specifically binds to
      the sequence juxtaposed to the AP-1-like site. Scatchard analyses show that this
      sequence, TTAGTTAC, forms two different complexes with K(d)s of 1.9 x 10(-10) and
      2.3 x 10(-9) M, respectively. Together, these results suggest that EGF/Ras/Raf
      induces transcription via combined activation of ATF3/c-Jun and a 52-kDa nuclear
      factor, whereas JunD acts as a repressor of this response.

PMID- 9269901
TI  - Overexpression of transforming growth factor beta type I receptor abolishes
      malignant phenotype of a rat bladder carcinoma cell line.
AB  - Transforming growth factor beta1 (TGF-beta1), a potent growth inhibitor of
      bladder carcinoma cells, elicits its effects by binding to cell surface
      receptors. LMC19, a highly invasive and metastatic rat bladder carcinoma cell
      line, was insensitive to the growth-suppressive effect of TGF-beta1, and it
      expressed undetectable levels of TGF-beta type I receptor (TbetaRI) mRNA by
      reverse transcription-PCR and its protein by Western blot analysis. To evaluate
      the effect of TbetaRI in reducing the malignant phenotype, we transfected LMC19
      with an expression vector containing human TbetaRI cDNA. Stable transfection with
      the expression vector yielded five transfectants that expressed the introduced
      TbetaRI mRNA. The binding activity of TGF-beta1 to TbetaRI was restored in all of
      the transfectants. The growth of the transfectants on a plastic surface was
      markedly inhibited in the presence of TGF-beta1 in the culture medium (P <
      0.001), whereas the control cells (parental and transfectant with only neo gene)
      remained TGF-beta1 insensitive. The colony-forming efficiency of the
      transfectants was strongly reduced in soft agar medium containing 5% FCS (P <
      0.001) and was restored by the addition of a neutralizing anti-TGF-beta antibody.
      Furthermore, none of the transfectants tested formed tumors in athymic nude mice,
      whereas the control cells did so in all mice tested. These findings indicate that
      introduction of TbetaRI can revert a malignant phenotype to a less aggressive
      (even benign) phenotype in a rat bladder carcinoma cell line that lacks TbetaRI,
      and that reduced expression of TbetaRI may be associated with the development and
      progression of bladder carcinomas.

PMID- 9269902
TI  - Stable integration of an mdx skeletal muscle cell line into dystrophic (mdx)
      skeletal muscle: evidence for stem cell status.
AB  - We have previously described a method for the derivation of long term cultures of
      undifferentiated myoblasts from the skeletal muscle of dystrophic (mdx) mice (J.
      Smith and P. N. Schofield, Exp. Cell Res., 210: 86-93, 1994). We now show that a
      clonal mdx-derived skeletal muscle cell line labeled with a retrovirus conferring
      beta-galactosidase activity and G418 resistance (PD50A) is capable of
      incorporation into mdx skeletal muscle myofibers for up to 14 months with no
      incidence of tumor formation. After a lag period of 5 days, injected PD50A cells
      disperse throughout the injected tibialis anterior muscle and take up satellite
      cell positions on the perimeter of myofiber bundles. PD50A cells begin to
      incorporate into fused muscle syncitium as early as 8 weeks after injection and
      persist for at least 14 months. We have rederived myoblasts expressing beta
      galactosidase from PD50A-injected muscles 12 months after injection,
      demonstrating that a reserve of mononuclear proliferation-competent PD50A cells
      are present in host muscle up to a year after their original introduction. These
      data support the contention that myoblasts derived by this culture method are
      functionally representative of a class of skeletal muscle "stem cells" and thus
      have potential both as agents for cellular therapy of intransigent diseases such
      as Duchenne muscular dystrophy as well as being a useful tool for the further
      investigation of normal muscle development.

PMID- 9269904
TI  - Cytokeratins and the evaluation of tumor differentiation in squamous lesions of
      the uterine cervix.
AB  - The differential expression of cytokeratins in epithelial or squamous cells has
      been demonstrated to be altered during the process of carcinogenesis. This
      altered expression of cytokeratins (CKs) may be closely related with epithelial
      differentiation and may remain stable in malignant tumors. In the present study
      an analysis using two monoclonal antibodies, CK 8.12 antibody specific for CK
      type 13 and 16 and CK 8.60 antibody specific for CK type 1, 10 and 11 was done in
      different grades of lesions in the uterine cervix. Changes from the normal
      expression pattern were seen in high grade Squamous intraepithelial lesions (SIL)
      (CIN-2/3) and invasive squamous cell carcinoma (SCC). No conspicuous difference
      in the staining expression between normal/benign cervical tissue and low grade
      SIL (CIN-I) was evident. Statistical analysis also revealed a significant
      correlation between the expression of these CK types to the differentiation
      status of the cervical lesions analyzed. Alterations in the expression of these
      CKs can be correlated to the differentiation pathway which may be deregulated
      during cervical carcinogenesis. The findings of the present study suggest that
      the expression of CK types 13 and 16 and 1, 10 and 11 using CK 8.12 and CK 8.60
      antibodies respectively may serve as markers of differentiation in cervical
      squamous neoplasms.

PMID- 9269903
TI  - Alterations of p53 gene in soft tissue and bone tumors.

PMID- 9269905
TI  - Findings of computerized nuclear morphometry of papillary thyroid carcinoma in
      correlation with the age of the patients.
AB  - The aim of this study was to evaluate the usefulness of nuclear morphometry in
      the pathology of papillary thyroid carcinoma by computer-aided image analysis and
      the statistical comparison of nuclear morphometric parameters with the age of
      patients. Seventy cases of papillary thyroid carcinoma diagnosed by fine needle
      aspiration (FNA) biopsies were classified into two groups according to the
      patients' age (group I: <45 years and group II: >45 years). The following six
      nuclear morphometric parameters were measured in a large number of randomly
      selected nuclei of each case: area, perimeter, major axis length, elongation,
      roundness, and compactness. The statistical analysis was performed by using
      special algorithms, and the results of the two groups were compared for each of
      the parameters measured using the t-test. Area, perimeter, and major axis length
      of papillary thyroid carcinoma nuclei demonstrate a statistically significant
      correlation with the age of patients, whereas elongation, roundness, and
      compactness did not show any correlation. Nuclear morphometry in association with
      the follow-up of patients could be suggested as an important prognostic index for
      papillary thyroid carcinoma.

PMID- 9269906
TI  - Stereologic estimates of volume-weighted mean nuclear volume in colorectal
      adenocarcinoma: correlation with histologic grading, Dukes' staging, cell
      proliferation activity and p53 protein expression.
AB  - Colorectal cancer has been studied from the point of view of the relationships
      between several variables, including proliferative activity and p53 protein
      expression. However, stereologic evaluation of nuclear size has not been
      thoroughly described. In the present study, measurements of the volume-weighted
      mean nuclear volume (nuclear Vv), have been performed in well, moderately and
      poorly differentiated colorectal adenocarcinomas and correlated with the Dukes'
      stage and other factors such as proliferative activity and p53 protein
      immunoreactivity. Although the mean values of nuclear Vv were higher in poorly
      differentiated cancers or Dukes' C&D stage than in well and moderately
      differentiated tumors or Dukes' A&B stage, these differences were not
      significant. However, the variability of nuclear size in colorectal cancers was
      more relevant than the mean values of nuclear Vv with respect to their invasive
      classification. The carcinomas which extended beyond the serosa (Dukes' stage
      C&D) had higher biologic variation than those grouped as Dukes' stage A&B. The
      results of the present study also indicate that nuclear size in colorectal
      cancers has a positive correlation with both proliferative activity and p53
      protein expression. The relationship between nuclear Vv and proliferative
      activity emphasizes the possible prognostic relevance of this stereologic
      estimate of nuclear size in colorectal adenocarcinoma.

PMID- 9269907
TI  - The mixed type in Lauren's classification of gastric carcinoma. Histologic
      description and biologic behavior.
AB  - Of 198 gastric carcinomas, resected at the Surgical Department, Leipzig
      University between 1986 and 1995, 28 cases were classified as mixed type
      according to Lauren's classification. These cases were examined in respect to
      morphologic features associated with biologic behavior. Contrary to the
      intestinal and diffuse type carcinomas, the mixed type carcinomas showed a deeper
      infiltration of the gastric wall (pT, P < 0.001), a higher metastatic rate to
      regional lymph nodes (pN, P < 0.05), and the need of higher staging at the UICC
      classification system (P < 0.05). Histologically, it is possible to establish
      four distinct groups; the first group shows a combination of intestinal and
      diffuse features, the second shows more diffuse structures with a nodular growth
      pattern, the third group shows both a glandular pattern and signet ring cells. In
      the fourth group, the tumors reveal an excessive production of mucin. The authors
      conclude that this subclassification of the mixed type of gastric carcinomas is
      useful for a better understanding and interpretation of these tumors.

PMID- 9269908
TI  - Lymphocytic mastitis and fibrosis of the breast in long-standing insulin
      dependent diabetics. A histopathologic study on diabetic mastopathy and report of
      ten cases.
AB  - Diabetic mastopathy represents less than 1% of benign breast diseases, but is
      more frequent (13%) in insulin-dependent diabetics. We report on 10 cases (eight
      females and two males) of this rare lesion of the breast in patients with
      additional diabetes mellitus type I. All cases showed a marked B-lymphocytic
      mastitis in combination with a homogenous fibrosis of the breast and with
      presence of epithelioid fibroblasts. In the male patients, diabetic mastopathy
      simulated gynecomastia. A comparative examination of 12 cases of lymphocytic
      mastitis without long-standing type-I-diabetes mellitus revealed a more
      heterogeneous pattern with lower degrees of inflammation and fibrosis. From the
      pathophysiologic point of view, lymphocytic mastitis in diabetic mastopathy is
      thought to be a diabetes-induced reaction probably of autoimmune origin.
      Moreover, lymphocytic mastitis with or without diabetes mellitus may represent a
      lymphoepithelial lesion of the MALT-type which, under certain circumstances, is
      considered to bear a prelymphomatous potential.

PMID- 9269909
TI  - Metanephric adenoma of the kidney: histologic, immunohistochemical and DNA
      content analysis study. A case report.
AB  - Metanephric adenoma is an uncommon and distinct clinicopathologic entity,
      recently described among benign epithelial kidney tumors. The authors report a
      case of a metanephric adenoma in a 70-year-old man. Because of its benign
      clinical course, it is important to distinguish metanephric adenoma from renal
      cell carcinomas and adult Wilms' tumor for which it is usually mistaken.
      Clinical, pathologic features and diagnostic problems of the case are discussed.

PMID- 9269910
TI  - Sarcomatoid chromophobe cell renal carcinoma: immunohistochemical and lectin
      study in one case.
AB  - We present one case of sarcomatoid chromophobe cell renal carcinoma with an
      indolent clinical course and assume that the carcinomatous component may affect
      the biologic behavior. The patient was a 61-year-old man who underwent right
      radical nephrectomy for a 11.2 cm tumor in the lower pole. The
      immunohistochemical findings demonstrate that EMA and cytokeratins 8 and 18 are
      useful markers for the sarcomatoid fraction, and the lectin study shows a loss of
      surface blood antigen. Chromophobe cell carcinoma may convert into sarcomatoid
      carcinoma. The existence of sarcomatoid renal cell carcinoma as a distinct entity
      should be re-considered.

PMID- 9269911
TI  - Vascular abnormalities of the uterus, concerning a case of diffuse cavernous
      angiomatosis of the uterus.
AB  - A case of diffuse cavernous angiomatosis of the uterus after delivery is
      reported. Owing to suspicion of abruptio placentae, cesarean section was
      performed. In the course of this section, several hematomas were noted in the
      myometrium, making total hysterectomy necessary. In view of this case,
      etiopathogenesis, causes and dynamics of clinical manifestation, possible
      complications, differential diagnosis and opportunities for the clinical
      diagnosis of uterine vascular abnormalities are discussed.

PMID- 9269912
TI  - Renal perineurioma in childhood.
AB  - Perineurioma of the kidney in a 7-year-old girl is described. The tumor in the
      upper pole was discovered during the evaluation of a urinary tract infection. The
      neoplasm measured 2.6 cm and radiographically it mimicked a nephroblastoma. The
      diagnosis of perineurioma was confirmed with histologic, immunohistochemical, and
      ultrastructural studies. These revealed findings typical of perineurioma of other
      locations. Histopathologically, differential diagnosis may include
      nephroblastoma, mesoblastic nephroma, neurofibroma, schwannoma, malignant
      peripheral nerve sheath tumor with perineural cell differentiation, and other
      benign and malignant mesenchymal tumors with spindle cell pattern. To the best of
      our knowledge, we report a unique renal perineurioma in a child.

PMID- 9269940
TI  - Resident cardiac mast cells and the cardioprotective effect of ischemic
      preconditioning in isolated rat heart.
AB  - Our study was designed to investigate the role of resident cardiac mast cells in
      the cardioprotective effect of ischemic preconditioning. Ischemic/compound 48/80
      preconditioning and treatment with compound 48/80, a mast cell degranulator (1
      microg/ml), produced cardioprotective and antiarrhythmic effects in isolated
      perfused rat heart subjected to 30-min global ischemia followed by 30-min
      reperfusion. Four episodes of ischemic/compound 48/80 preconditioning and
      compound 48/80 treatment markedly reduced the release of lactate dehydrogenase
      (LDH) and creatine kinase (CK) in coronary perfusate and the incidence of
      ventricular premature beats (VPBs) and ventricular tachycardia or fibrillation
      (VT/VF) during the reperfusion phase. The release of mast cell peroxidase (MPO),
      a marker of mast cell degranulation in coronary perfusate, increased immediately
      after ischemic and compound 48/80 preconditioning. The cardioprotective and
      antiarrhythmic effect of ischemic/compound 48/80 preconditioning was lost within
      60 min. It is proposed that the cardioprotective effect of ischemic
      preconditioning, which lasts for 60 min in isolated rat heart, may be ascribed to
      degranulation of resident cardiac mast cells.

PMID- 9269941
TI  - Effects of pemirolast and tranilast on intimal thickening after arterial injury
      in the rat.
AB  - We previously reported that tranilast, an antiallergic agent, reduced intimal
      thickening after endothelial injury in rats. In this study, to verify whether or
      not antiallergic agents inhibit intimal thickening, we investigated the effect of
      pemirolast on intimal thickening after endothelial injury and compared its effect
      with that of tranilast. Administration of two antiallergic agents, pemirolast
      (0.1, 1, and 10 mg/kg, p.o.) and tranilast (300 mg/kg, p.o., daily), was begun 2
      days before endothelial injury and continued until the animals were killed.
      Endothelial injury in the rat femoral artery was induced by a photochemical
      reaction between localized irradiation by green light and intravenously
      administered rose bengal. To evaluate intimal hyperplasia, we measured the cross
      sectional area of the intima 21 days after endothelial damage. Pemirolast at
      doses of 0.1, 1, and 10 mg/kg reduced the intimal area to 2.10 +/- 0.33, 1.36 +/-
      0.19, and 1.35 +/- 0.18 (x0.01 mm2), respectively, and tranilast showed a
      tendency to reduce the intimal area, which was 1.86 +/- 0.35 x 0.01 mm2, compared
      with findings for controls (2.83 +/- 0.49 x 0.01 mm2). In rat A10 vascular smooth
      muscle cells, we investigated the effects of antiallergic agents on migration by
      using a modified Boyden chamber assay and on proliferation by using the
      bromodeoxyuridine-incorporation assay. Two antiallergic agents inhibited in a
      concentration-dependent manner both migration and proliferation of smooth muscle
      cells stimulated by platelet-derived growth factor. These results suggest that
      antiallergic agents directly inhibit migration of smooth-muscle cells to the
      intima from the media and proliferation in the intima, and that pemirolast has
      more potent antihyperplastic action than does tranilast. Antiallergic agents may
      be effective in preventing restenosis after coronary angioplasty.

PMID- 9269942
TI  - Characterization of bunazosin-sensitive alpha1-adrenoceptors in human renal
      medulla.
AB  - We studied the characteristics of bunazosin-sensitive alpha1-adrenoceptors in
      human renal medullae by using renal-clearance studies and radioligand-binding
      assay. In 12 patients with hypertension, renal-clearance studies demonstrated
      that bunazosin significantly increased renal blood flow from 683 +/- 82 (SD) to
      829 +/- 103 ml/min (p < 0.05) and decreased renal vascular resistance from 0.18
      +/- 0.02 to 0.14 +/- 0.02 mm Hg/(ml/min) (p < 0.05), but that prazosin had little
      effect on renal function. In a radioligand-binding assay, specific, saturable,
      and stereoselective [3H]bunazosin binding, with a single class of binding sites
      (Kd = 2.7 +/- 1.4 nM; Bmax = 44 +/- 16 fmol/mg protein; n = 11) was detected in
      membrane preparations of human renal medullae. The rank order of potency of
      antagonists that inhibited [3H]bunazosin-binding was bunazosin (Ki in nM = 49) >
      prazosin (57) > yohimbine (3,900) > propranolol (29,000), and that of agonists, l
      norepinephrine (7,400) > l-epinephrine (19,000) > d-norepinephrine (71,000). The
      competition curves fit a one-site model. These findings suggest that bunazosin
      sensitive alpha1-adrenoceptors exist in human renal medullae and participate in
      the regulation of renal hemodynamics.

PMID- 9269943
TI  - Differential signaling pathways in platelet-activating factor-induced
      proliferation and interleukin-6 production by rat vascular smooth muscle cells.
AB  - Vascular smooth muscle cells (SMCs) can be induced to proliferate in response to
      several cytokines and growth factors, including interleukin (IL)-6. Platelet
      activating factor (PAF) also has been shown to induce SMC proliferation. Because
      PAF can stimulate IL-6 production in monocytes, macrophages, and endothelial
      cells, our study was undertaken to determine whether PAF could induce IL-6
      production by SMCs and to define the underlying signaling pathways. Exposure of
      rat aortic SMCs to picomolar concentrations of PAF resulted in enhanced
      production of IL-6. The effect was concentration dependent, selective for the
      active form of PAF, and mediated by specific PAF receptors. Pretreatment of the
      cells with Bordatella pertussis toxin (PTX) prevented the effect of PAF,
      suggesting the involvement of alpha i-type subunits of G proteins in the signal
      transduction pathway. PAF-dependent IL-6 production was also prevented by
      inhibition of tyrosine kinases with genistein or erbstatin. Inhibition of
      eicosanoid production by blocking either phospholipase A2 or cyclooxygenase also
      abrogated the effect of PAF on IL-6 production. Moreover, inhibition of Ca2+
      calmodulin activity with W7 or blocking of calcium channels with verapamil or
      nifedipine prevented PAF-mediated enhancement of IL-6 production. Whereas PAF
      induced signal-transduction pathways leading to IL-6 production and SMC
      proliferation were partially common, they appeared to diverge downstream of PLA2
      activation: inhibition of cyclooxygenase had no effect on proliferation, whereas
      augmentation of cyclic adenosine monophosphate (cAMP) levels or activation of
      protein kinase A inhibited proliferation, in contrast to IL-6 production. Our
      findings suggest a role for PAF in modulating vascular function by stimulating
      local production of IL-6 by SMCs and promoting their proliferation. The two
      effects are, however, associated with partially divergent signaling pathways and
      may not be causally related.

PMID- 9269944
TI  - Fixed combination of benazepril and low-dose amlodipine in the treatment of mild
      to moderate essential hypertension: evaluation by 24-hour noninvasive ambulatory
      blood pressure monitoring.
AB  - The antihypertensive efficacy and tolerability of a fixed combination of
      benazepril (10 mg) and low-dose amlodipine (2.5 mg) were assessed in 24 patients
      (mean age, 43.9 years) with uncomplicated mild to moderate essential hypertension
      [supine diastolic blood pressure (DBP) > or = 95 and < or = 120 mm Hg)]. After 2
      weeks of washout taking placebo, patients were randomized to receive the fixed
      combination or placebo, both administered once daily for 3 weeks, according to a
      double-blind, crossover design. Patients were checked at the end of the washout
      period and every 3 weeks thereafter. At each visit, 24-h ambulatory BP monitoring
      (ABPM) was performed by a noninvasive device (Spacelabs 90207); casual BP (by
      mercury sphygmomanometer), heart rate (HR), and body weight also were measured.
      The fixed combination significantly reduced systolic (SBP) and DBP values
      throughout the 24 h as compared with placebo, without affecting the normal BP
      circadian variability. The antihypertensive effect of the fixed combination could
      be observed to a similar extent during the day and night and was still
      significant 24 h after dosing. HR and body weight were not affected by the
      treatment. The fixed combination of benazepril 10 mg/amlodipine 2.5 mg was well
      tolerated, and no patient withdrew from the study because of side effects.

PMID- 9269945
TI  - High D-glucose induces alterations of endothelial cell structure in a cell
      culture model.
AB  - Diabetes mellitus leads to micro- and macroangiopathy with endothelial
      dysfunction. To investigate the direct influence of high glucose on endothelial
      cell structure and possible pharmacologic effects, seven different experimental
      protocols were carried out on endothelial cells in culture. There were four
      control groups with either 5 mM D-glucose alone, 5 mM D-glucose plus 15 mM L
      glucose (for osmotic control), 5 mM D-glucose plus 500 nM celiprolol, or 5 mM D
      glucose plus 57 nM nitrendipine. Three experimental groups had either 20 mM D
      glucose alone, 20 mM D-glucose plus 500 nM celiprolol or 20 mM D-glucose plus 57
      nM nitrendipine. Treatment of all groups started at the third passage of the
      cells and lasted until confluence was reached (5-8 days). The endothelial cells
      were fixed in paraformaldehyde and stained either with hematoxylin-eosin
      solution, with nitro blue tetrazolium for nicotinamide adenine dinucleotide
      phosphate (NADPH)- diaphorase staining, or actin staining with phalloidin was
      carried out. For quantitative analysis of the histologic specimens, the slides
      were viewed via a microscope and a videocamera. The pictures were converted
      digitally and could be analyzed with the videopicture-analyzing system, JAVA. In
      the four control groups, neither treatment with 15 mM L-glucose nor
      administration of celiprolol or nitrendipine had an effect on cell, cytoplasm,
      and nuclear area. The number of giant or polynuclear cells and the histochemical
      NADPH-diaphorase activity were not altered. Incubation of endothelial cells with
      20 mM D-glucose for 5-8 days resulted in a significant increase in total and
      cytoplasmic area, as well as in the number of giant and polynuclear cells,
      whereas the nuclear area and the NADPH-diaphorase activity were significantly
      reduced. Concomitant treatment with celiprolol was able to reverse these
      alterations in endothelial structure significantly but had only a weak effect on
      the NADPH-diaphorase. Nitrendipine had no beneficial effect on the high D-glucose
      induced cell alterations. The actin staining of the control cells showed the
      typical actin pattern with most of the actin filaments arranged at the periphery
      of the cells. Administration of 20 mM D-glucose resulted in a disturbance of the
      actin pattern, with most of the actin filaments now arranged in the middle of the
      cells. However, neither celiprolol nor nitrendipine exhibited a significant
      influence on this altered actin structure. High D-glucose treatment over several
      days thus leads to severe changes in endothelial cell structure, and celiprolol
      may have a beneficial effect on these hyperglycemia-induced cell alterations.

PMID- 9269946
TI  - Beneficial actions of preconditioning and stretch on postischemic contractile
      function of isolated working rat heart: effects of staurosporine.
AB  - Preconditioning is commonly induced by a brief ischemic insult; myocardial
      stretch can trigger this protection by an unknown mechanism. Myocardial stretch
      preconditions the in vivo canine heart; however, the existence of a stretch
      induced protection in the rat heart remains unknown. The purpose of this study
      was to test this myocardial protection induced, in isolated working rat heart, by
      global ischemia and stretch initiated by a transient increase in the left
      ventricle (LV). Isolated rat hearts underwent 30 min of global ischemia followed
      by 30 min of reperfusion. Before this, hearts received a 15-min period of either
      no intervention (control; C), 5 min of global ischemia + 10 min of reperfusion
      (preconditioning; PC) or 5 min of stretch + 10 min with no intervention (stretch;
      S). Stretch was induced by a transient increase in LV preload from 5 to 20 cm
      H2O. LV work started under a afterload of 80 cm H2O. Control, PC, and S hearts
      received either no drug (untreated) or staurosporine (50 nM), a protein kinase C
      inhibitor, before the "preconditioning" period. Creatine kinase (CK) release,
      ventricular fibrillation during reperfusion, and postischemic recovery of
      contractile function (aortic flow) were the end points of the study. In the S
      group, the abrupt increase in preload resulted in a significant increase of
      aortic flow (42 +/- 2 to 47 +/- 2 ml/min; p < 0.05). During the 30-min
      reperfusion period, control hearts displayed a poor recovery of contractile
      functions (8 +/- 3 ml/min, 30 min after reflow, versus 40 +/- 2 ml/min at
      baseline; p < 0.05). Both untreated PC and S groups exhibited a significant
      reduction in CK release, incidence of ventricular fibrillation (55% of control
      hearts developed persistent VF vs. 6% in both the PC and S groups), and
      postischemic dysfunction during reperfusion (p < 0.05 vs. control). Staurosporine
      prevented these beneficial effects in PC and S groups. Our study suggests that
      myocardial protection can be induced by stretch in the isolated working rat
      heart, likely through activation of protein kinase C. In conclusion, our results
      show that ischemic preconditioning and stretch had comparable favorable effect on
      functional recovery after a sustained ischemic insult in the isolated rat heart.

PMID- 9269948
TI  - Roles of NO-synthase and cyclooxygenase in sex- and pregnancy-dependent arterial
      and venous pressures in the rat.
AB  - The roles of NO synthase (NOS) and cyclooxygenase on vascular pressures were
      studied as a function of sex and pregnancy. After anesthesia, mean arterial
      pressure (MAP) and mean circulatory filling pressure were lower in pregnant rats
      compared with male and virgin rats, but N(G)-nitro-L-arginine methyl ester (L
      NAME; 30 mg/kg) induced similar increases in MAP. Pithing abolished these
      pressure differences, suggesting a diminished autonomic reflex in pregnancy, and
      led in pregnant rats to a lower arterial and venous NO modulation. In separately
      perfused mesenteries, the lower responses to KCI observed in venous beds of
      female compared with male rats do not involve any dysfunction of NOS activity in
      the mesenteries isolated from virgin and pregnant rats. The cyclooxygenase
      pathway is implicated in the KCl-induced responses of vessels taken from male
      rats and of venous mesentery from pregnant rats. But prostanoids do not share in
      the acetylcholine (ACh)-induced relaxations in the arterial and venous K+
      contracted mesenteric vasculatures isolated from any of the groups of rats.

PMID- 9269947
TI  - Prevention of coronary vascular abnormalities early in reperfusion with TGF-beta
      may not prevent late coronary vascular injury.
AB  - Endothelial injury, manifest by increased protein leak and decreased endothelium
      dependent relaxation, occurs during reperfusion after ischemia. Transforming
      growth factor-beta (TGF-beta) has been shown to improve endothelium-dependent
      relaxation and reduce infarct size after short periods (from 20 min to 4.5 h) of
      reperfusion even when administered 24 h before the ischemic period. However,
      whether this represents a transient delay in the process leading to endothelial
      injury or prevention of injury has not been clear. To examine this issue, we
      measured protein leak, an index of coronary microvascular permeability, and
      endothelium-dependent relaxation, a measure of coronary endothelial function,
      after brief (1-h) and lengthy (48-h) reperfusion periods in dogs treated 30 min
      before ischemia with TGF-beta (30 microg/kg, i.v.) and control dogs. The left
      anterior descending coronary artery (LAD) was ligated for 1 h followed by 1 h of
      reperfusion (n = 10) or 48 h of reperfusion (n = 12). Protein leak was assessed
      by a dual-isotope technique by using radiolabeled transferrin and erythrocytes,
      and endothelium-dependent relaxation was assessed in epicardial coronary rings by
      using adenosine diphosphate (ADP), an endothelium-dependent vasodilator, and
      sodium nitroprusside (SNP), an endothelium-independent dilator. In control
      animals, there was a marked increase in the protein leak index (PLI) in the
      infarct zone (8.3 +/- 1.4 in 1-h dogs, and 8.7 +/- 0.9 in 48-h dogs) compared
      with the nonischemic myocardium (3.1 +/- 0.8 at 1 h, and 3.8 +/- 0.9 at 48 h). In
      TGF-beta treated dogs, there was a marked improvement in PLI in the infarct zone
      in 1-h dogs (PLI, 4.1 +/- 1.1; p < 0.05; or a 50% reduction compared with
      untreated dogs). However, the 48-h dogs treated with TGF-beta failed to
      demonstrate an improvement in PLI (PLI, 8.5 +/- 0.9; p = NS). Endothelium
      dependent relaxation was impaired in the LAD in control dogs, and treatment with
      TGF-beta failed to improve relaxation after 1 or 48 h of reperfusion.
      Microvascular permeability was increased and endothelium-dependent relaxation was
      decreased after ischemia at both 1 and 48 h of reperfusion. Pretreatment with TGF
      beta reduced the increase in permeability at 1 h of reperfusion but not at 48 h.

PMID- 9269949
TI  - Ionic mechanism responsible for prolongation of cardiac action-potential duration
      by berberine.
AB  - This study was designed to investigate the effects of berberine on membrane
      currents forming the repolarization phase of action potentials in isolated guinea
      pig ventricular myocytes by using the patch-clamp technique. Application of
      berberine (3-30 microM) to the current-clamped myocytes produced a significant
      prolongation of action-potential duration (APD), which was concentration
      dependent. However, this agent (3-30 microM) did not affect the resting potential
      and action-potential amplitude. The prolongation of APD caused by berberine was
      not attenuated by tetrodotoxin (TTX, 10 microM), and TTX (10 microM) failed to
      shorten APD in cells pretreated with 30 microM berberine. Under the voltage-clamp
      conditions, berberine (3-30 microM) inhibited the delayed rectifier K+ currents
      (I(K)). Under conditions in which the rapidly activating components (I(Kr)) and
      slowly activating component (I(Ks)) were dissected out, berberine was shown to
      block I(Ks) without affecting I(Kr). Application of berberine (3-30 microM)
      increased the Na+-Ca2+ exchange currents, which were completely abolished by 5 mM
      NiCl. The L-type Ca2+ currents (I(Ca)) also were increased by 3-30 microM
      berberine, but the threshold potential, the potential at which I(Ca) was maximal,
      and the apparent reversal potential remained unchanged. Berberine at either 3 or
      30 microM did not affect the inward rectifier K+ currents. This study suggests
      that the prolongation of cardiac repolarization by berberine is mainly caused by
      the inhibition of I(Ks) and increase of I(Ca).

PMID- 9269950
TI  - Comparison of hemodynamic effects of nitric oxide (NO) donors with different NO
      releasing properties in rats.
AB  - The aim of this study was to compare the hemodynamic effects of three nitric
      oxide (NO) donors [i.e., (+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3
      hexenamide (FK409), (+/-)-N-[(E)-4-ethyl-3-[(Z)-hydroxyimino]-6-methyl-5-nitro-3
      he ptenyl]-3-pyridinecarboxamide (FR 146801) and isosorbide dinitrate (ISDN)] in
      rats. In in vitro experiments, FK409 had a higher spontaneous NO-releasing rate
      in solution and more potent vasorelaxant activity in isolated rat aorta than
      other drugs. FR146801 and ISDN showed almost the same vasorelaxant activity. In
      in vivo experiments, FK409 significantly decreased hematocrit at 1.0 mg/kg p.o.,
      whereas FR146801 and ISDN significantly decreased it at 10 mg/kg p.o., suggesting
      that these NO-donating agents cause significant plasma volume expansion. However,
      only FK409 showed significant hypotensive effects immediately after oral
      administration even at 0.32 mg/kg; FR146801 and ISDN did not cause any
      significant hypotension at 10 mg/kg, suggesting that FK409 induces much more
      potent arterial vasodilation than other drugs. These findings suggest that NO
      donors induce significant plasma volume expansion and that the differences in the
      selectivities between these effects and their hypotensive effects is probably
      produced by their different NO-releasing activities.

PMID- 9269951
TI  - Electrical and mechanical effects of a novel antihypertensive quinazoline
      derivative, 3-[[4-(2-methoxyphenyl) piperazin-1-ly]methyl]-5-(methylthio)-2,3
      dihydroimidazo [1,2-c]quinazoline, on guinea pig ventricular muscles.
AB  - Electrical and mechanical effects of 3-[[4-(2-methoxyphenyl)piperazin-1
      ly]methyl]-5-(methylthio)-2,3-+ ++dihydroimidazo[1,2-c]quinazoline (DL-017), a
      new synthesized antihypertensive agent, were studied in guinea-pig ventricular
      papillary muscles. In muscle fibers driven at 1 Hz, DL-017 decreased the twitch
      force in a concentration-dependent manner and significantly increased the action
      potential duration and decreased intracellular Na+ activity (ai(Na)) and maximal
      rate of upstroke of action-potential (Vmax) when concentrations were greater than
      1 microM. Phenylephrine in the presence of 1 microM propranolol produced a
      concentration-dependent positive inotropy. DL-017 (0.01 microM) antagonized the
      positive inotropic effect of phenylephrine and shifted the concentration-response
      curve to the right. In K+-depolarized muscle fibers, 0.1 microM DL-017
      significantly decreased the contractile force without changing the slow action
      potential. In low-[K+]o and high-[Ca2+]o solutions, a train of stimuli triggered
      a spontaneous rhythm that could be abolished by 3 microM DL-017. Our results
      suggest that DL-017 not only exhibits an alpha1-antagonistic effect but also
      induces negative inotropy by a decrease in myofibrillar calcium sensitivity and
      inhibits Na+ channels at higher concentrations, contributing to the drug's
      negative inotropic and type-I antiarrhythmic effects.

PMID- 9269952
TI  - Time delay of cell death by Na+/H+-exchange inhibition in regionally ischemic,
      reperfused porcine hearts.
AB  - Studies in different preparations have suggested that Na+/H+ exchange is one
      mechanism causally involved in cell death in myocardial ischemia and reperfusion.
      The time delay of cell death by pretreatment with the Na+/H+-exchange inhibitor
      HOE642, cariporide (4-isopropyl-3-methylsulphonylbenzoyl-guanidine
      methanesulphonate), was investigated in regionally ischemic, reperfused porcine
      hearts. HOE642 (1 mg/kg) was injected intravenously in 14 thoracotomized pigs 10
      min before occlusion of the left anterior descending coronary artery (45 min of
      ischemia, six pigs; 70 min of ischemia, six pigs; 90 min of ischemia, two pigs).
      Ischemia was followed by 24 h of reperfusion. Six animals (45 min of ischemia)
      served as controls. Infarct size was determined as a ratio of infarcted
      (tetrazolium stain, histology) to ischemic myocardium (dye technique), and
      regional myocardial function was assessed by sonomicrometry. HOE642 did not
      affect global hemodynamic parameters. In the pretreated group with 45 min of
      ischemia, HOE642 significantly decreased histochemical infarct size from 51.2 +/-
      12.6% (control group) to 13.2 +/- 12% (p < 0.005) and histologic infarct size
      from 44.5 +/- 9% to 17.1 +/- 7% (p < 0.005). Recovery of regional systolic
      shortening after 24 h of reperfusion was improved from 2 +/- 6% (control group)
      to 12 +/- 7% (p = 0.02). In addition, myocardial contracture and increase in
      heart rate during early reperfusion were attenuated. When ischemia was prolonged
      to 70 min after pretreatment with HOE642, infarct size, recovery of systolic
      shortening, myocardial contracture, and increase in heart rate did not differ
      from those of the control group. Pretreatment with HOE642 increased the tolerance
      to ischemia/reperfusion by approximately 20-25 min. Inhibition of Na+/H+ exchange
      appears to be very promising in the clinical treatment of acute myocardial
      ischemia and reperfusion.

PMID- 9269953
TI  - Effects of clonidine and flesinoxan on blood pressure variability in conscious
      spontaneously hypertensive rats.
AB  - The effects of two centrally acting antihypertensive agents, clonidine (0.1
      mg/kg/day s.c.) and flesinoxan (1 mg/kg/day s.c.), on short-term blood pressure
      variability (BPV) were investigated in conscious spontaneously hypertensive rats
      (SHRs). The drugs were infused subcutaneously during 24 h and 4 weeks by osmotic
      minipumps. BPV was characterized by spectral analysis. In conscious SHRs,
      clonidine significantly and preferentially reduced the low frequency (LF; 0.25
      0.75 Hz) oscillations of mean arterial pressure (MAP) in short-term (24 h) and
      long-term (4 weeks) treatments but significantly decreased MAP level only in
      short-term treatments. In contrast, flesinoxan significantly reduced MAP level
      whatever the duration of infusion but decreased LF-MAP only in short-term
      treatments. These results show that centrally mediated inhibition of sympathetic
      tone by stimulation of either alpha2-adrenoceptors or 5-HT1A (serotonin)
      receptors can reduce BPV. This effect is independent of the modifications in BP
      level. The effects of the drugs on baroreceptors may also contribute to the
      decrease in BPV. The dual properties of clonidine (alpha2-adrenoceptors and
      imidazoline receptors) may account for its differential effects on BP level and
      BPV.

PMID- 9269954
TI  - Loss of acetylcholine-induced relaxation by M3-receptor activation in mesenteric
      arteries of spontaneously hypertensive rats.
AB  - This study investigated which subtype of muscarinic receptor in mesenteric
      arteries from SHRs mediates the loss of the release of nitric oxide (NO) or
      endothelium-derived hyperpolarizing factor (EDHF) in spontaneously hypertensive
      rats (SHRs) and Wistar-Kyoto (WKY) rats. After SHRs and WKY rats were killed,
      their superior mesenteric arteries were isolated to perform the vascular
      relaxation study. Acetylcholine (ACh, 1 nM-1 microM)-induced relaxation was in a
      concentration-dependent manner and was impaired in mesenteric arterial rings
      obtained from the SHR group, whereas nitroglycerin (10 nM-1 microM)-induced
      relaxation was not affected in endothelium-denuded rings obtained from the
      hypertensive rat. In the presence of N(omega)-nitro-L-arginine (L-NNA; 0.1 mM) or
      methylene blue (10 microM), the ACh-induced relaxation was partially attenuated
      in both SHRs and WKY rats. The relaxation of ACh was partially inhibited by 4
      aminopyridine (4-AP; 1 mM), apamin (APM; 1 microM), or charybdotoxin (CTX; 0.1
      microM) in WKY rats, whereas that relaxation was not affected by 4-AP, APM, or
      CTX in SHRs. However, the L-NNA-resistant relaxation of ACh was further inhibited
      by APM or CTX in WKY rats but not in SHRs. When arterial rings were precontracted
      by 60 mM K+, the ACh-induced relaxation was not significantly different in SHRs
      and WKY rats. However, this relaxation was abolished by L-NNA (0.1 mM) in both
      strains. In addition, the M3 muscarinic antagonist, 4-diphenylacetoxy-N
      methylpiperidine was the most potent in inhibiting the relaxation of ACh, being
      more potent than pirenzepine and methoctramine, which preferentially block M1 and
      M2 receptors in the mesenteric artery of WKY rats, respectively. 2-Nitro-4
      carboxyphenyl-N,N-diphenylcarbamate (1 microM) almost abolished the relaxation of
      ACh, but not of A23187, in SHRs and WKY rats. These results suggest that NO and
      EDHF are released from the endothelium of rat mesenteric artery on the activation
      of muscarinic M3-receptor by ACh, and the loss of ACh-induced relaxation in small
      arteries of SHRs is mainly through reducing the release or activity or both of
      EDHF.

PMID- 9269956
TI  - Antagonism of the GPIIb/IIIa receptor with the nonpeptidic molecule BIBU52:
      inhibition of platelet aggregation in vitro and antithrombotic efficacy in vivo.
AB  - The glycoprotein (GP) IIb/IIIa (the alphallb beta3 integrin) found on platelets
      binds fibrinogen or von Willebrand factor when the platelet is activated, thereby
      mediating the aggregation of platelets. Blockade of the GPIIb/IIIa should prevent
      platelet aggregation independent of the substance or substances responsible for
      activating the platelets. This comprehensive inhibition of platelet aggregation
      is thought to be an effective therapeutic approach to various clinical
      thromboembolic syndromes. This study investigated the platelet inhibition
      provided by blocking GPIIb/IIIa by using a new nonpeptidic molecule, BIBU52, in
      both in vitro and in vivo models. BIBU52 competes with [125I]fibrinogen for
      binding sites on human platelets in a Ca2+ and pH-dependent manner with a 50%
      inhibitory concentration (IC50) of 35 +/- 12 nM. BIBU52 inhibited the aggregation
      of human platelets in platelet-rich plasma induced by collagen (1-2 microg/ml),
      adenosine diphosphate (ADP; 2.5 microM), and a thrombin receptor-activating
      peptide (TRAP; SFLLRNPNDKYEPF-NH2; 25 microM) with IC50 values of 82, 83, and 200
      nM, respectively. The inhibition of platelet aggregation by BIBU52 was found to
      be highly species dependent. BIBU52 inhibited aggregation in plasma from rhesus
      and marmoset monkeys with an IC50 of 150 nM but was totally ineffective in rat
      plasma. The selectivity of BIBU52 for inhibiting GPIIb/IIIa in comparison with
      other adhesion molecules was investigated in a human endothelial cell adhesion
      assay. The adhesion of human endothelial cells to matrices of vitronectin,
      fibronectin, collagen I, or laminin was not affected by concentrations as high as
      100 microM BIBU52; thus BIBU52 demonstrates a high selectivity for the human
      GPIIb/IIIa. The antithrombotic effect of BIBU52 in vivo was investigated in three
      animal models of recurrent arterial thrombus formation. In the guinea pig aorta,
      BIBU52 inhibited thrombus formation dose dependently, with lack of thrombus
      formation for 1 h after a bolus dose of 1.0 mg/kg i.v.. Both acetylsalicylic acid
      and dazoxiben were less effective in this model. In pigs with recurrent thrombus
      formation in the carotid artery, 1.0 mg/kg i.v. also inhibited thrombus
      formation. Heparin was not effective in the pig, and acetylsalicylic acid was
      only partially effective. In the pig, the dose of 1.0 mg/kg i.v. BIBU52 also was
      associated with a 70% inhibition of collagen-induced platelet aggregation ex vivo
      but with only a transient prolongation of sublingual bleeding time to a maximum
      of 2.5-fold and without other hemodynamic effects. In the marmoset monkey, a dose
      of 10 microg/kg i.v. could abolish recurrent arterial thrombosis. Hemodynamic
      effects of BIBU52 in anesthetized pigs were not detected in doses < or = 10
      mg/kg. These data demonstrate that BIBU52 is a potent and selective antagonist of
      the human GPIIb/IIIa receptor and capable of substantial inhibition of platelet
      aggregation in vitro and ex vivo as well as inhibition of arterial thrombus
      formation in vivo in animal models of thrombosis.

PMID- 9269955
TI  - Pharmacokinetic-pharmacodynamic model relating spiraprilat plasma concentrations
      to systemic and regional hemodynamic effects in congestive heart failure.
AB  - The aim of this study was to investigate the relations between the plasma
      concentrations of spiraprilat (the active metabolite of the angiotensin
      converting enzyme inhibitor spirapril) and its effects on plasma converting
      enzyme activity (PCEA), pulmonary capillary wedge pressure (PCWP), and brachial
      blood flow (BBF), after a single oral administration of 6 mg of spirapril in
      eight patients with severe congestive heart failure (CHF). Concentrations and
      effects were determined before and repeatedly during 48 h after drug intake. A
      sigmoid model was fitted to individual observations. Maximal effects,
      concentrations inducing half-maximal effects, and Hill coefficients were -99 +/-
      2%, 3.9 +/- 1.9 ng/ml, and 2.4 +/- 0.7 for PCEA inhibition, -15 +/- 8 mm Hg, 11.8
      +/- 9.2 ng/ml, and 2.6 +/- 1.3 for PCWP decrease, and 36 +/- 19 ml/min, 13.8 +/-
      7.6 ng/ml, and 3.3 +/- 1.0 for BBF increase. In severe CHF, although a 14 ng/ml
      plasma concentration of spiraprilat may induce a 95% inhibition of PCEA, a 30
      ng/ml plasma concentration is mandatory to normalize PCWP and BBF. This
      concentration corresponds to the peak achieved after a 6-mg oral dose of
      spirapril.

PMID- 9269957
TI  - Efficacy of the straight endorectal pull-through in the management of familial
      adenomatous polyposis--a 16-year experience.
AB  - From 1979 to 1995, 27 patients who had familial adenomatous polyposis (FAP) were
      treated at the authors' institution. Most patients (n = 23) presented as a result
      of a previous family history of FAP. Eighteen patients presented with symptomatic
      colonic disease that included bloody stools (n = 14), diarrhea (n = 10), and
      abdominal pain (n = 6). Treatment consisted of a total colectomy, rectal
      mucosectomy, and straight endorectal pull-through (ERPT) in 26 of 27 patients.
      One patient preferred to undergo an ileoanal J pouch reconstruction. A temporary
      diverting loop ileostomy was performed in 25 patients and closed at an average of
      100 days after the ERPT. Follow-up has been achieved in 100% of the patients and
      ranges from 6 to 182 months with an average of 48 months. Postoperative
      complications included partial bowel obstruction (two patients, one requiring
      enterolysis); and mild pouchitis (one patient). Two of the 27 patients required
      proctectomy and permanent ileostomy procedures, one for rectal cancer that was
      present microscopically in the initial rectal specimen from the ERPT and the
      other because of recurrent anastomotic complications. No patient required
      revision of the straight pull-through to a pouch or takedown of the pull-through
      as a result of persistent diarrhea or dissatisfaction. All of the patients are
      continent, and 80% deny any soiling during bouts of gastroenteritis. The mean
      number of bowel movements reported was 10 per day at the first postoperative
      clinic visit with a gradual decreased to six per day after 2 years. Initial use
      of bulking (62%) and antimotility agents (88%) decreased significantly over the
      course of follow-up to 29% and 67%, respectively at the most recent follow-up
      (average, 48 months) of each patient. Pelvic sepsis, which occurs in 8% of most
      series of patients who have pouches, did not occur in any of our patients.
      Pouchitis, a common complication with pouches (23%), occurred in only one of the
      patients and was mild and easily treated medically. This series demonstrates that
      total colectomy with rectal mucosectomy and straight ERPT eliminates the risk of
      colorectal cancer and achieves continence with a low complication rate and
      excellent functional results and patient satisfaction.

PMID- 9269958
TI  - The effect of iatrogenic vas deferens injury on fertility in an experimental rat
      model.
AB  - The long-term result of accidental crushing of the vas deferens during inguinal
      surgery is unpredictable. It is stated that even a slight disturbance in the
      muscular layer or mucosa may endanger fertility. This study was designed to
      investigate the early and late histopathologic changes of iatrogenic injury on
      the vas and its effect on fertility in a rat model. Both vasa deferentia of 54
      male rats, divided into three groups (n = 18 each), were subjected to an
      operative manipulation. These manipulations consisted of digital compression for
      45 seconds in group A, grasping with a mosquito clamp for 2 seconds in group B,
      and grasping with a mosquito clamp for 2 minutes in group C. In five rats from
      each group, the vasa were removed on the third and 21st postoperative day for
      histological evaluation. The remaining 13 rats in each group were allowed to mate
      for a period of 4 months. Bilateral vasa were analyzed for patency and histology.
      A spermatic granuloma was observed in 79% of the fertile and 80% of the infertile
      rats. Statistical analysis showed no significant fertility difference among the
      three groups. There was no statistical difference between groups B and C (P >
      .05) in terms of high and low flow patency rates in vitro, whereas a statistical
      significance was present between these two groups and group A (P< .001). It can
      be said that type rather than time of injury is important in this experimental
      model, because the results of the patency test alone are sufficient to prove the
      possibility of functional damage in vas deferens. The authors conclude that
      inguinal contents should be handled carefully and contralateral exploration in
      asymptomatic cases older than 1 year with inguinal pathology should be avoided.

PMID- 9269959
TI  - Laparoscopic-assisted pneumatic reduction of intussusception.
AB  - The nonoperative treatment of intussusception is done by fluoroscopy, however,
      false-positive and negative images may lead to unnecessary operations. The aim of
      this study was to evaluate the feasibility of laparoscopy in pneumatic reduction.
      Surgical ileoileocolic intussusception was performed in 27 dogs. Sixteen dogs
      were observed for 3 days (group A), and 11 were observed for 5 days (group B).
      Laparoscopy was performed in the intussuscepted dogs during pneumatic reduction.
      Under general anesthesia, a 10-mm trocar was inserted supraumblically in the
      midline, and the laparoscope was introduced. The intussuscepted bowel was
      observed on the video monitor. A 5-mm trocar was inserted in the right upper
      quadrant. The mesentery of the terminal ileum was manipulated using grasping
      forceps to assist reduction. CO2 was insufflated into the rectum using a Foley
      catheter, and the reduction was observed on the video monitor. The success rate
      was 94% (mean reduction time, 2.5 minutes +/- 1.0) for group A and 100% (mean
      reduction time, 3.7 minutes +/- 0.8) for group B. Bowel perforation was observed
      in one dog, and recurrence of intussusception in another. The authors claim that
      observing the bowel on the video monitor may help in the differential diagnosis
      and reduction of difficult cases such as ileoileocolic and delayed
      intussusceptions. Therefore, unnecessary open surgery may be prevented.

PMID- 9269960
TI  - The effect of arginine supplementation on growth hormone release and intestinal
      mucosal growth after massive small bowel resection in growing rats.
AB  - Four-week-old male Sprague-Dawley rats underwent a 90% small bowel resection.
      From the fourth day after surgery, they were divided into group 1 and 2, and pair
      fed by elemental diets (0.8 kcal/mL, 50 mL/day) with L-arginine (n = 10) or L
      glycine (n = 11) as an isonitrogenous and isoenergetic supplement for 3 weeks.
      They were compared with each other 3 weeks after surgery. A statistical analysis
      was performed using the unpaired Student's t test and the one-way factorial
      analysis of variance (ANOVA) using Bonferroni/Dunn multiple comparison test. A
      Pvalue of < .05 was considered significant. There were no significant differences
      between the two groups in food intake, body weight, tail length, residual ileal
      length, and plasma IGF-I level. However, the mean height of ileal villi in group
      1 showed higher than that in group 2 (P < .01). Growth hormone-releasing hormone
      (GHRH) provocative tests (1 microg per rat, intravenously) showed the more
      significant elevation of growth hormone IGH) secretion in the arginine supplement
      group than that of glycine supplement group at 5 minutes (P < .05). There were no
      significant differences between basal levels of plasma rat GH in both groups. It
      is suggested that arginine has a possible significant role of GH secretion and
      intestinal mucosal growth after massive small bowel resection.

PMID- 9269961
TI  - Latissimus dorsi flap procedures to cover myelomeningocele in utero: a
      feasibility study in human fetuses.
AB  - There is experimental and clinical evidence that in utero repair of
      myelomeningocele (MMC) may preserve neurological function. In five aborted human
      fetuses (gestational age, 18 to 29 weeks), the authors tested whether proximally
      and distally based latissimus dorsi flaps (LDF) can be used to cover MMC lesions.
      Fetal soft tissues were developed enough to allow surgical handling, preparation
      of both flap types was technically easy, and the vascular pedicles could be
      preserved. The proximally pedicled LDF was suitable to cover the upper spine from
      lower cervical to lower thoracic levels, whereas the distally pedicled LDF was
      suitable to cover the spine between lower thoracic and lower sacral levels. These
      results suggest that various LDF procedures are technically feasible in early
      gestational human fetuses and could be used for in utero repair of MMC.

PMID- 9269962
TI  - The relationship between disturbed transit and dilated bowel, and manometric
      findings of dilated bowel in patients with duodenal atresia and stenosis.
AB  - To determine whether dilated bowel proximal to obstruction associated with
      duodenal atresia and stenosis is related to feeding problems after a surgical
      correction of obstruction, the authors reviewed retrospectively the degree of
      bowel dilatation and disturbed transit as well as other clinical features in 18
      duodenal atresia and 12 duodenal stenosis patients. A multivariate analysis was
      conducted to determine the possible correlation among them. The authors also
      evaluated the physiological function of the dilated bowel in duodenal atresia and
      stenosis patients (n = 8) by manometry of dilated bowel. The results were as
      follows. (1) In multivariate analysis, using the degree of disturbed transit as a
      dependent variable and using other clinical features as independent variables,
      the presence of postoperative complication and the existence of bowel dilatation
      2 weeks after the operation were risk factors for disturbed transit. (2) One or
      two episodes of phase 3 were found in six of eight measured patients during the
      recorded period. The most distinctive manometric finding was the low contraction
      amplitude of both phase 2 and phase 3. These results indicate that dilated bowel
      was related to disturbed transit during the postoperative period, and that the
      low contraction amplitude of the dilated bowel was the main pathophysiological
      feature. The tapering or plication of dilated bowel might be indicated in
      patients with a markedly dilated bowel.

PMID- 9269963
TI  - Maintenance of fetal murine pulmonary microvasculature in heart-lung en bloc
      whole organ culture.
AB  - The authors have previously shown that murine fetal lungs can be maintained in
      serum-free whole organ culture and that airway ligation accelerates lung
      development. In spite of extensive use of lung organ culture systems, the
      vasculature of the unperfused lung in organ culture has not been studied. The aim
      of the present study was to compare organ cultures of heart-lung blocks with
      continuous perfusion of the pulmonary vasculature to those without perfusion, ie,
      whole lungs cultured without the attached heart. Time-dated pregnant CD-1 mice
      were killed on gestational day (Gd) 14. The fetuses were removed via laparotomy.
      Heart-lung blocks and whole lungs without the heart were excised under sterile
      conditions and cultured in BGJb media. Some of the heart-lungs and whole lungs
      underwent tracheal ligation whereas others were left with the trachea unligated
      allowing free egress of airway fluid. After 7 days, the cultured organs were
      processed for histology, ultrastructural analysis, and immunohistochemistry. (1)
      Lungs were fixed in 10% formalin, paraffin embedded, and processed for routine
      H&E staining. (2) Lungs were fixed in 2.5% glutaraldehyde in cacodylate buffer
      and processed for transmission electron microscopy. (3) Lungs were embedded in
      CRYOform and flash frozen for immunohistochemical localization of PECAM-1 (CD31)
      (PECAM-1, Platelet endothelial cell adhesion molecule-1, a selective endothelial
      cell marker). Our daily observations of the cultured organs showed that the heart
      maintained synchronized beating for all 7 days in culture. Perfusion of the
      pulmonary microvasculature was demonstrated. Light microscopically, H&E sections
      showed that fresh fetal Gd14 pseudoglandular lungs (time-zero) had a defined
      capillary network, which was more centrally localized and peripherally less
      developed. The presence of more numerous lung capillaries in the cultured heart
      lung blocks was noted when compared with cultured lungs alone. Ultrastructurally,
      endothelial cells with intact structural integrity were identified only in
      cultured whole lungs with hearts. Immunohistochemical staining of the whole lungs
      with rat antimurine PECAM-1 monoclonal antibody performed on cryosections showed
      the presence of vasculature by specific PECAM-1 localization on endothelial
      cells. PECAM-1 labeling of capillaries was noted in Gd14 (time-zero) lungs. In
      addition, the lungs cultured with hearts, ie, perfused lungs, showed more well
      defined, distinct capillary networks stained with PECAM-1 antibody than
      unperfused lungs without hearts. Our results showed that microvasculature is
      present in murine fetal lungs at Gd14. After 7 days in organ culture, the
      maintenance of lung microvasculature was confirmed histologically,
      ultrastructurally, and immunohistochemically. The microvasculature in whole lungs
      cultured as perfused/beating heart-lung blocks was better maintained than the
      microvasculature of unperfused whole lungs cultured without hearts. A perfused
      whole lung organ culture model is attractive because the lung architecture is
      better maintained and may be useful in lung developmental studies as it mimics
      the in situ heart-lung functional physiological relationship.

PMID- 9269964
TI  - Blunt abdominal trauma in children: risks of nonoperative treatment.
AB  - This retrospective study includes 203 children who had intraabdominal injuries
      after blunt trauma, mainly bicycle accidents and falls. Of 145 patients with
      splenic injury, seven underwent surgery. There was a 100% splenic salvage rate.
      Twenty-nine children had hepatic injury and four underwent laparotomy. One
      patient who was initially treated conservatively had a complicated clinical
      course with rebleeding that led to two laparotomies. Three of 10 pancreatic
      injuries were operated on; one of them 4 weeks after the trauma because of a
      pseudocyst. Nineteen patients had gastrointestinal tract injuries. Of seven
      intramural hematomas, five were treated nonoperatively. Twelve patients had
      gastrointestinal perforations. Seven underwent laparotomy without delay. Three
      patients underwent surgery 24 hours after admission because of severe abdominal
      rigidity or pneumoperitoneum. There was one case of severe in-hospital delay in
      which splenic and hepatic injuries were thought to account for the physical
      findings. At laparotomy 36 hours after admission, a jejunal rupture and necrosis
      of the transverse colon were found. Nonoperative management of blunt abdominal
      trauma has been very successful regarding splenic ruptures. Conservative
      management of hepatic injuries is more hazardous, and treatment of pancreatic
      injuries is a matter of controversy. Gastrointestinal-tract perforations are
      difficult to diagnose and important to bear in mind while keeping a conservative
      attitude toward abdominal trauma.

PMID- 9269965
TI  - Mutation analysis of p53 gene in childhood malignant solid tumors.
AB  - Alterations of the p53 gene have been extensively investigated in a wide variety
      of human malignancies. However, data on childhood malignant solid tumors are
      still limited. Mutations of the p53 gene on exons 5 through 8 were examined in 82
      childhood malignant solid tumors by the polymerase chain reaction-single-strand
      conformation polymorphism (PCR-SSCP) method, and the nature of these mutations
      was confirmed by direct sequencing. The 82 tumors examined included
      neuroblastomas (n = 44), Wilms' tumors in = 13), hepatoblastomas (n = 11),
      rhabdomyosarcomas (n = 10), extraosseus Ewing sarcomas (n = 2), undifferentiated
      sarcoma of the liver (n = 1), and fibrosarcoma (n = 1). Two sarcoma samples were
      identified as having point mutations. One was a rhabdomyosarcoma with a missense
      mutation at codon 273, substituting histidine (His) for arginine (Arg). Another
      was an undifferentiated sarcoma of the liver with a missense mutation at codon
      245, substituting serine (Ser) for glycine (Gly). No mutations were detected
      among neuroblastomas, Wilms' tumors, or hepatoblastomas. The two sarcomas with
      mutations were localized tumors. Both patients who had these tumors are disease
      free for 8 and 5 years after treatment, respectively. The overall incidence of
      p53 mutations was low (2.4%, 2 of 82). However, the incidence, when calculated
      for sarcomas, was higher at 14.3% (2 of 14). These data indicate that p53
      mutations are generally uncommon in childhood malignant solid tumors examined.
      However, in some childhood sarcomas, p53 mutations appear to have a causative
      role in the development of these tumors.

PMID- 9269966
TI  - Outcome of treatment for pediatric sarcoma of the foot: a retrospective review
      over a 20-year period.
AB  - Soft tissue sarcomas (STS) arising in the foot are rare in children. From 1975 to
      1994, 18 children (median age, 13.5 years) were treated at St Jude Children's
      Research Hospital for STS of the foot. Five children had rhabdomyosarcoma (RMS),
      with alveolar histology in four cases. All of these patients presented with
      metastatic disease, which proved fatal within 9 to 24 months despite combined
      modality treatment with chemotherapy, radiation, and surgery. Thirteen patients
      had nonrhabdomyosarcoma soft tissue sarcoma (NRSTS). The most common histological
      variant was synovial sarcoma (7 patients). Of the 10 who presented with localized
      disease, seven survived 1 to 12 years (median, 7 years). Surgical treatment for
      these consisted of local excision (n = 2), wide local excision (n = 3), below
      knee amputation (n = 1 ), ray amputation (n = 1). Three received supplemental
      radiation, and one was also treated with chemotherapy. Local or distant
      recurrence proved fatal in the three other children who had localized disease.
      Three children who presented with metastatic NRSTS died 8 to 14 months after
      diagnosis. All surviving patients are without significant functional disability.
      In our experience, pediatric RMS of the foot has a poor outcome, attributable to
      both alveolar histology and presence of metastatic disease at diagnosis. In
      contrast, NRSTS of the foot is more often localized, and limited surgery with
      adjuvant radiation in the absence of clear margins should be the treatment of
      choice.

PMID- 9269967
TI  - Improved results in patients who have congenital diaphragmatic hernia using
      preoperative stabilization, extracorporeal membrane oxygenation, and delayed
      surgery.
AB  - Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypoplasia.
      The pulmonary vascular bed may be extremely reactive to various stimuli, and in
      the treatment it is important to avoid pulmonary vasospasm. The strategy in our
      institution since 1990 has involved a prolonged preoperative stabilization with
      gentle mechanical ventilation. Pressures have been kept as low as possible, and
      slight hypercarbia has been accepted. Peak inspiratory pressures exceeding 35 cm
      H2O have been avoided. Extracorporeal membrane oxygenation (ECMO) has been used
      according to standard inclusion criteria. Nitric oxide and high-frequency
      oscillation have been added to the therapeutic modalities during the study
      period. When the patient was considered stabilized, surgical repair was
      undertaken after a delay of 24 to 96 hours. In patients on ECMO who could not be
      decannulated, surgical repair was undertaken while on ECMO. From 1990 through
      1995, 52 patients were admitted with a diagnosis of CDH. Forty-three of these
      were risk group patients presenting with respiratory distress within 6 hours
      after birth. A total of 48 patients survived (survival rate 92%), and 39 of the
      risk group patients (survival rate 91%). There were only four hospital deaths,
      all with contraindications to ECMO. It is suggested that the adopted protocol is
      beneficial in the treatment of CDH and that the fraction of patients who have
      pulmonary hypoplasia incompatible with life is smaller than previously believed.

PMID- 9269968
TI  - New aspects in a murine model for extrahepatic biliary atresia.
AB  - The cause of extrahepatic biliary atresia (EHBA) remains unknown, and even an
      animal model is still lacking. Observations in a murine infectious model (newborn
      Balb/c mice infected with rhesus rotavirus group A [RRV]) reported extrahepatic
      biliary obstruction similar to findings in children who have EHBA. In the present
      study, this animal experiment was repeated, and the clinical and histomorphologic
      changes were observed over 3 weeks. Eighty-nine newborn mice were infected with
      RRV, and 67% showed signs of cholestasis and delayed growth. Eight of these
      animals recovered spontaneously whereas the others remained icteric. Fourty-six
      pups were prepared for microscopic examination following a 2-day interval. From
      the fifth day, the whole biliary tract showed edematous swelling with cellular
      infiltration. Ten days later, in the extrahepatic bile duct, a transformation
      took place in which concentric infiltration led to complete obstruction,
      sometimes with prestenotic dilatation. The intrahepatic changes showed reactive
      necrosis and proliferation of the small bile ducts. In one 19-day-old mouse, a
      ballooning dilatation was observed, similar to a developing choledochal cyst.
      Infection with RRV induces in newborn Balb/c mice a cholestatic clinical picture
      with different courses of the disease leading mostly to complete biliary
      obstruction and secondary hepatic changes similar to EHBA in children. This is
      the first animal model for EHBA with complete obstruction of the extrahepatic
      bile duct induced by infection. These findings present a new basis for further
      studies.

PMID- 9269969
TI  - Pediatric blunt abdominal trauma: role of computed tomography vascular blush.
AB  - Nonoperative management of blunt abdominal trauma is widely accepted in pediatric
      patients. There are few factors prospectively available to predict reliably which
      children will not respond to nonoperative treatment. Computed tomography scans
      demonstrating a vascular contrast blush are associated with arterial bleeding and
      the failure of nonoperative management of splenic injuries in adults. The authors
      describe five hemondynamically stable pediatric patients who have intraabdominal
      injury and a characteristic vascular contrast blush who acutely did not respond
      to nonoperative treatment. Vascular blush may be an indication for early
      laparotomy in pediatric trauma patients.

PMID- 9269971
TI  - Children with Hirschsprung's disease have an abnormal colonic mucus defensive
      barrier independent of the bowel innervation status.
AB  - The mucus gel layer in the colon plays an important role in the defensive
      mechanisms against pathogenic organisms. Mucin glycoproteins or mucins are the
      major component of this gel. We studied the mucins in patients who had
      Hirschsprung's disease (HD) by colonic mucosal organ culture with radioactive
      mucin precursors [35S]-sulphate and [3H]-glucosamine. The secreted and cellular
      mucus fractions were collected after 24-hour incubation, and mucins were purified
      by gel filtration. The ratio of incorporation of the precursors and their
      turnover were quantified. Purified mucins were tested against wheat germ
      agglutinin for total mucin turnover. We used nine aganglionic bowel samples, 10
      ganglionic bowel samples from HD patients, and 13 age-matched normal controls.
      There were no significant differences in the three groups in ratio of
      incorporation. The turnover with both radioactive precursors was reduced in both
      aganglionic and ganglionic bowel of HD, these differences were significant in
      [35S]-sulphate incorporation in the cellular fraction, ganglionic bowel being
      most affected. Total mucin turnover, as assessed by reactivity with wheat germ
      aggultinin, was reduced in both HD groups, being significant in the cellular
      fraction, aganglionic bowel being the most affected. These results signify an
      abnormal mucus defensive barrier in the colon of HD patients, even in the
      ganglionic bowel, which is thought to be normal and is retained at the definitive
      pull-through operation. This abnormality may be an etiological factor in the
      pathogenesis of enterocolitis of HD.

PMID- 9269970
TI  - Impact of the development of a liver transplant program on the treatment of
      biliary atresia in an institution in Japan.
AB  - Kasai operation for biliary atresia (BA) and living-related liver transplantation
      (LRLT) for failed Kasai cases have been performed by the same team in our
      hospital. Outcome of the treatment for BA in the pretransplantation and
      posttransplantation era in our institution were compared. As the "pre" group, 35
      children first underwent the Kasai operation between 1982 and 1989. The "post"
      group consisted of 25 patients who underwent Kasai after introduction of the LRLT
      program in our hospital (1990). As for the reconstruction procedure after portal
      dissection during Kasai, jejunal interposition hepatic portoduodenostomy for the
      pre group was intentionally changed to Roux-en-Y procedure for the post group to
      decrease the risk of duodenal leakage after LRLT. Patients who needed revision of
      the Kasai decreased from 57% for the pre group to 28% for the post group. There
      was only one re-revision in the post group compared with seven in the pre group.
      In the pre group, 10 patients (28.6%) died at age 6 to 16 (mean, 8.5) months
      before the transplantation program was initiated. In the pre group, three
      patients could receive a cadaveric liver transplantation in other countries, and
      seven had LRLT in our hospital. Ten patients (40%) in the post group had LRLT at
      7 to 22 (mean, 9.3) months old, and no deaths occurred in this group. When the
      patients who had liver dysfunction were excluded, the percentage of the patients
      who could be expected to survive and accomplish growth without undergoing liver
      transplantation was similar for the two groups, (31.4% v 36%). The change in the
      reconstruction procedure and the tendency for fewer revisions of Kasai procedure
      were effects of the start of the liver transplant program. As a general strategy
      for BA, Kasai operation should be the initial procedure, followed by liver
      transplantation for failed Kasai. In the late-diagnosed patients, primary LRLT
      can be considered if the liver has already been cirrhotic. LRLT in the infantile
      period is a significant component of this strategy for helping all patients to
      survive.

PMID- 9269972
TI  - Partial liquid ventilation and nitric oxide in congenital diaphragmatic hernia.
AB  - PURPOSE: In congenital diaphragmatic hernia (CDH) there is immature lung
      development with a resulting clinical picture of pulmonary hypoplasia, surfactant
      deficiency, and pulmonary hypertension. Pulmonary hypoplasia and surfactant
      deficiency both have been successfully treated using partial liquid ventilation
      (PLV). Pulmonary hypertension associated with CDH has proven difficult to treat,
      but inhaled nitric oxide, which is a potent highly selective pulmonary
      vasodilator, may have potential. The aim of this study was to assess PLV in CDH
      and to document the effect of nitric oxide when administered through
      perfluorocarbon. METHODS: This study using the lamb CDH model consisted of two
      groups; a conventional mechanically ventilated (CMV) group and a PLV group. At 1
      and 3 hours, nitric oxide (80 ppm) was given for 15 minutes. Data collected
      included blood gases, pulmonary function tests, pulmonary and systemic blood
      pressure. RESULTS: After 30 minutes of ventilation, blood gases in the PLV group
      were all significantly improved (P < .001): pH, CMV 6.92 +/- 0.15 versus PLV 7.24
      +/- 0.11; P(CO2), CMV 139 +/- 26 mmHg versus PLV 52 +/- 11 mmHg; P(O2), CMV 26 +/
      15 mmHg versus PLV 184 +/- 60 mmHg. In addition, there was a significant
      increase in dynamic compliance and a reduction in pulmonary hypertension. Nitric
      oxide was only efficacious in the PLV group, causing a further increase in
      oxygenation and a decrease in pulmonary hypertension. These effects were reversed
      when the nitric oxide was stopped. CONCLUSION: This study shows that PLV both
      improves gas exchange and pulmonary mechanics in CDH and allows the effective
      delivery of nitric oxide to reduce the pulmonary hypertension associated with
      CDH.

PMID- 9269973
TI  - Neurological outcome is diminished in survivors of congenital diaphragmatic
      hernia requiring extracorporeal membrane oxygenation.
AB  - In a series of 61 infants who had congenital diaphragmatic hernia (CDH) treated
      at our center from 1978 through 1996, 37 of 59 (61%) survived the perioperative
      period with two infants lost to follow-up. Nine (47%) of 19 infants survived
      before the introduction of extracorporeal membrane oxygenation (ECMO) into our
      region in 1986. Since 1986, 28 (70%) of 40 infants survived. Eighteen infants
      required ECMO, and 12 (75%) survived. A chart review was performed to determine
      whether infants surviving CDH are suffering from delays in neurological
      development, and, if so, whether this is attributable to ECMO. Of 12 ECMO
      survivors, 8 (67%) exhibited functional or anatomic evidence for neurological
      delay. Of 21 non-ECMO survivors, where adequate follow-up was available to make
      an assessment of neurological development, five (24%) exhibited evidence for
      delay. This difference was significant (P < .05, Fisher's Exact test). Of these
      five infants, three were premature, and one had DiGeorge syndrome. More ECMO
      survivors required diaphragmatic (67%) and abdominal (67%) patches at the time of
      diaphragmatic repair than non-ECMO survivors (4% and 12%, respectively; P < .05,
      Fisher's Exact test). In addition, more ECMO survivors required gastrostomy tube
      placement for feeding (50%) than non-ECMO survivors (16%; P < .05, Fisher's Exact
      test). A greater need for Nissen fundoplication in ECMO survivors (42%) than in
      non-ECMO survivors (12%) approached significance (P = .05, Fisher's Exact test).
      There were trends toward higher 1 and 5 minute APGAR scores and initial and best
      preoperative P(O2) in the non-ECMO survivors. A comparison between ECMO survivors
      who exhibited evidence of neurological delay with those who did not showed no
      differences in duration of ECMO, incidence of intracranial complications during
      ECMO, need for gastrostomy tube feeding or Nissen fundoplication, or incidence of
      carotid artery repair between the two groups. Infants surviving CDH who require
      ECMO have a greater incidence of neurological delay than those who do not. This
      is likely because of severity of the presenting illness as reflected by a greater
      need for diaphragmatic and abdominal patches during diaphragmatic repair, the
      need for Nissen fundoplication and gastrostomy tube feeding, and a trend toward
      poor APGAR scores and best preoperative P(O2) levels in these patients. However,
      there may be characteristics of ECMO, as yet unidentified, that may contribute to
      this outcome.

PMID- 9269975
TI  - Accurate placement of central venous catheters in pediatric patients using
      endocavitary electrocardiography: reassessment of a personal technique.
AB  - To avoid the need for radiological control in the assessment of the proper
      location of central venous catheters (CVC), a particular use of endocavitary
      electrocardiography (EC-ECG) was proposed 10 years ago. The aim of this study is
      to reassess our experience with this method. EC-ECG assumes that the CVC, when
      filled with normosaline and connected to a standard electrocardiograph, behaves
      like an exploring electrode. The approach of the catheter tip to the right atrium
      is then detected by a slightly increasing negative P wave. When the tip reaches
      the exact level of the sinus node, the P wave suddenly deepens. After a
      preliminary test of the reliability of the technique versus the standard method
      in 50 CVC placements verified by both EC-ECG and chest x-ray, we have placed 807
      CVCs in children using EC-ECG only. There have been no false-positive and one
      false-negative test result (lead connector misplacement). In 17 cases in which
      intrinsic deflection was not detected, the catheter tip was found to be wrongly
      positioned; all the remainder CVCs have been successfully positioned. For 10
      years this technique has proved to be a simple, safe, quick, inexpensive and
      highly reliable method to assess the correct positioning of the CVC.

PMID- 9269974
TI  - Hirschsprung's disease: a 20-year experience.
AB  - During the period from 1972 to 1992, 59 children received surgical treatment at
      the University of Louvain Medical School for biopsy-proven Hirschsprung's disease
      (HD). The extent of aganglionosis was as follows: short segment restricted to the
      rectosigmoid or descending colon (n = 44, 75%); long segment (n = 9,15%); ultra
      short segment (n = 3, 5%); unknown length because of death without autopsy (n =
      3, 5%). The median age at operation was 7 months for short-segment disease
      compared with 14 months for those with long-segment disease. Surgical procedures
      used for short-segment disease were Swenson with colostomy (n = 16), Swenson
      Pellerin without colostomy (n = 27), Duhamel (n = 1), and for long-segment
      disease were Martin (n = 3), Swenson-Deloyers (n = 2), Swenson-Boley (n = 2) and
      ileostomy only in = 2). Lynn's sphincteromyotomy was performed in the three ultra
      short cases. There were six deaths (10%) at a median age of 86 days (range, 28 to
      1545 days), three had long-segment disease, and the others were not classified
      because of death before curative surgery. Enterocolitis (EC) was the most common
      cause of death (five cases) and was also the major source of morbidity after
      curative surgery (12 of 44, 27%) in short-segment patients, three of seven (43%)
      in long-segment patients. The functional success of the procedure was evaluated
      in 70% of the surviving patients (37 of 53; mean follow-up, 8.7 years; range, 1.2
      to 21.5), using a novel semiquantitative scoring system, specifically designed
      for children who have HD. This system assesses normal stool evacuation, abdominal
      distention, soiling, and severe incontinence. The results were compared with
      those from a population of 39 healthy children and adolescents and demonstrated
      progressive improvement in function during childhood and adolescence (P = .04)
      for patients treated for short-segment disease. However, function was found to be
      consistently poorer in all age groups when compared with healthy controls (5 to
      10 years, P < .01; 10 to 15 years, P < .05; > 15 years, P < .01).

PMID- 9269976
TI  - Unique spindle cells in the involved ileal segment of rats with congenital
      aganglionosis.
AB  - Protein gene product (PGP) 9.5 is a newly characterized brain-specific protein
      originally detected by high-resolution two-dimensional electrophoresis of soluble
      human brain proteins. Immunoreactivity for PGP9.5 was investigated in the small
      and large intestine of aganglionic mutant and control rats with light microscopy,
      electron microscopy, and confocal laser scanning microscopy. Immunoreactive
      spindle-shaped cells were seen in the inner circular muscle layer of the
      aganglionic ileal segment. The long axes of these spindle cells paralleled the
      inner circular muscle fibers. PGP9.5-positive spindle cells were positive for
      enteric actin, and some of them were also positive for vimentin, a relatively
      specific marker for the special smooth muscle (pacemaker cells). These cells may
      prove to be a maldeveloped microenvironment of aganglionic segment. However, it
      is necessary to investigate expression of PGP9.5 in embryonal tissue with an
      abnormal environment to test this hypothesis. This study showed PGP9.5-positive
      pacemaker cells in the aganglionic ileal segment in the first time.

PMID- 9269978
TI  - Dysplastic nitrergic neurons in the rectum of a patient with rectal ectasia.
AB  - We present a histochemical study of resected colon from a 13-year-old boy
      diagnosed with rectal ectasia. Laminar preparations and sectioned tissue of
      rectum were assayed histochemically for nitric oxide (NO) synthase activity by
      reducing nitro blue tetrazolium salt in the presence of the cofactor NADPH.
      Tissue preparations displayed intensely labelled neurons and fibers throughout
      the gut wall. Laminar preparations of Meissner's plexus showed a hyperplasia of
      ganglia and NO-related neurons throughout the length of the resected rectum
      compared with normal bowel. Sectioned tissue of the Auerbach's plexus
      demonstrated a normal number of ganglia and NO-related neurons. As well, the
      ectatic bowel showed a proliferation of nerve fibers in keeping with the degree
      of circular smooth muscle hypertrophy. This proliferation may represent a
      reactive phenomenon secondary to the functional obstruction. The NO histochemical
      technique may form the basis of further investigations in defining the cause of
      this functional obstruction.

PMID- 9269977
TI  - Pediatric intestinal leiomyosarcomas: case report and review of the literature.
AB  - Primary intestinal leiomyosarcomas in children are rare tumors. Twenty-seven
      previous cases are documented in the literature with little information available
      on the treatment, survival, and prognostic factors surrounding these tumors. The
      authors report the 28th case of pediatric intestinal leiomyosarcoma and its
      follow-up, that of a newborn presenting with intestinal obstruction. Follow-up
      from all previously reported cases is not recorded and is needed. Our patient,
      like most children with this tumor, underwent complete excision with no evidence
      of recurrence at 5 years. Visceral metastases from these neoplasms are atypical,
      and recorded long-term prognosis may be favorable, unlike their counterpart in
      the adult population.

PMID- 9269979
TI  - Ectopic intrathyroidal thymus diagnosed as a solid thyroid lesion: case report
      and review of the literature.
AB  - The authors report a case of a 6-year-old boy in whom aberrant thymic tissue was
      misdiagnosed as an intrathyroidal solid lesion. The patient underwent
      hemithyroidectomy and did well. Because cervical ectopic thymus rarely produces
      symptoms, the true incidence in children is unclear. Surgeons need to consider
      this rare entity, not to mistake it as a thyroid neoplasm, and not to perform
      extensive thyroid resection.

PMID- 9269981
TI  - Epigastric cleft: a previously unreported entity.
AB  - A newborn who is believed to have an anterior midline abdominal wall fusion
      defect located in the epigastric region is presented, with a proposal of new
      nomenclature as "epigastric cleft."

PMID- 9269980
TI  - Hypocalcemia and hyperphosphatemia after phosphate enema use in a child.
AB  - The authors present a 3-year-old girl in whom severe hyperphosphatemia and
      hypocalcemia developed after the administration of three adult-sized hypertonic
      phosphate enemas. The commonly held notion that these enemas are not absorbed and
      therefore are systemically inactive is incorrect. With early intervention and
      treatment, the child survived without sequelae despite a serum phosphate level
      (74.7 mg/dL) that is greater than those previously reported. The treatment of
      hyperphosphatemia is reviewed as well as underlying pathology such as altered
      gastrointestinal motility and renal insufficiency, which may predispose the
      patient to this problem. Physicians should be aware of the possible adverse
      effects that can be caused by hypertonic phosphate enemas.

PMID- 9269982
TI  - A unique presentation of atypical complete duplication of terminal ileum, colon,
      rectum, and urinary bladder.
AB  - A unique case of complete duplication of urinary bladder, distal ileum, cecum,
      appendix, colon, and rectum with two mesocolons and separate vascular arcades is
      being reported.

PMID- 9269983
TI  - External carotid artery ligation for life-threatening hemorrhage in
      exsanguinating orbital facial congenital hemangiopericytoma.
AB  - A 7-week-old infant with a locally invasive, orbital, congenital
      hemangiopericytoma underwent emergency external carotid artery (ECA) ligation for
      exsanguinating hemorrhage from an intraoral biopsy site. ECA ligation was
      successful in controlling the life-threatening hemorrhage and in reducing tumor
      size and vascularity. The location and extensive nature of the tumor prevented
      primary excision. Preoperative adjuvant chemotherapy was unsuccessful in
      controlling tumor growth. After ECA ligation, with reduction in tumor bulk and
      blood supply, the tumor was radically excised. This technique has important
      implications in the management of patients with extensive hemangiopericytomas or
      sino-facial tumors previously regarded as unresectable and which present with
      life-threatening hemorrhage.

PMID- 9269984
TI  - Duodenal web presenting with acute pancreatitis.
AB  - An 8-year-old boy presented with acute pancreatitis and was found to have a
      fenestrated duodenal web (windsock) and associated anomalies. After partial
      excision of the web and duodenoplasty, he has remained well with no further
      symptoms.

PMID- 9269985
TI  - Adenocarcinoma of the esophagus in an 8-year-old boy.

PMID- 9269986
TI  - Daily cranial ultrasounds during ECMO: a quality review/cost analysis project.

PMID- 9269987
TI  - Pyloric atresia associated with intestinal atresia.

PMID- 9269988
TI  - Characterization of prostatic epithelial cell lines derived from transgenic
      adenocarcinoma of the mouse prostate (TRAMP) model.
AB  - To develop a syngeneic transplantable system to study immunotherapeutic
      approaches for the treatment of prostate cancer, three cell lines were
      established from a heterogeneous 32 week tumor of the transgenic adenocarcinoma
      mouse prostate (TRAMP) model. TRAMP is a transgenic line of C57BL/6 mice
      harboring a construct comprised of the minimal -426/+28 rat probasin promoter
      driving prostate-specific epithelial expression of the SV40 large T antigen.
      TRAMP males develop histological prostatic intraepithelial neoplasia by 8-12
      weeks of age that progress to adenocarcinoma with distant metastases by 24-30
      weeks of age. The three cell lines (TRAMP-C1, TRAMP-C2, and TRAMP-C3) express
      cytokeratin, E-cadherin, and androgen receptor by immunohistochemical analysis
      and do not appear to have a mutated p53. Although TRAMP-C1 and TRAMP-C2 are
      tumorigenic when grafted into syngeneic C57BL/6 hosts, TRAMP-C3 grows readily in
      vitro but does not form tumors. The T antigen oncoprotein is not expressed by the
      cell lines in vitro or in vivo. The rationale for establishing multiple cell
      lines was to isolate cells representing various stages of cellular transformation
      and progression to androgen-independent metastatic disease that could be
      manipulated in vitro and, in combination with the TRAMP model, provide a system
      to investigate therapeutic interventions, such as immunotherapy prior to clinical
      trials.

PMID- 9269989
TI  - Drug-induced apoptosis is associated with enhanced Fas (Apo-1/CD95) ligand
      expression but occurs independently of Fas (Apo-1/CD95) signaling in human T
      acute lymphatic leukemia cells.
AB  - Induction of apoptosis is considered to be the underlying mechanism that accounts
      for the efficiency of chemotherapeutic drugs. It has recently been proposed that
      induction of Fas ligand (FasL) expression with subsequent autocrine and/or
      paracrine induction of cell death through binding to the Fas (Apo-1/CD95)
      membrane accounts for chemotherapy-associated apoptosis. In the present study, we
      analyzed the significance of FasL expression in the mediation of drug-induced
      apoptosis in the T-acute lymphatic leukemia model CEM. In particular, we examined
      the potential of the tumor drugs fludarabine, doxorubicin, and cisplatin to
      induce FasL expression. We also raised the question of whether apoptosis induced
      by these drugs occurs through the Fas pathway and hence can be blocked by the
      cowpox virus protein CrmA, a specific inhibitor of this pathway. All tumor drugs
      examined led to an increase in FasL protein. However, overexpression of CrmA had
      no effect on drug-induced apoptosis. Moreover, neither incubation with inhibitory
      monoclonal antibodies against Fas that completely prevented Fas-induced apoptosis
      in these cells nor pretreatment with a monoclonal antibody to FasL affected drug
      induced cell death. Our observations suggest a Fas/FasL-independent mechanism for
      drug-induced apoptosis and exclude the involvement of caspase 1 and caspase 8 in
      this process in T-acute lymphatic leukemia cells.

PMID- 9269990
TI  - The DNA repair protein O6-methylguanine-DNA methyltransferase protects against
      skin tumor formation induced by antineoplastic chloroethylnitrosourea.
AB  - Chloroethylnitrosoureas (CNUs) are being used in the therapy of various
      neoplastic diseases, including skin cancer. Because secondary tumor formation is
      a serious threat in chemotherapy with these drugs, we explored whether and to
      what extent the DNA repair protein DNA-O6-methylguanine:protein-L-cysteine S
      methyltransferase (MGMT) protects against CNU-induced tumors. We made use of
      transgenic mice overexpressing human MGMT in their skin and the initiation
      promotion protocol on treatment with 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3
      (2-chloroethyl)-3-nitrosourea (ACNU, nimustine) that is representative of CNUs.
      ACNU applied topically as a single low dose to the dorsal skin was highly
      effective in tumor induction in nontransgenic mice, whereas in cytokeratin MGMT
      transgenic mice, tumor formation was remarkably reduced. ACNU-induced skin tumors
      harbored mutations in the c-Ha-ras gene in both groups of mice. The results
      provide clear evidence that MGMT exerts protection against CNU-induced cancer.
      Our data also indicate that O6-chloroethylguanine, which is repaired by MGMT, is
      a main precarcinogenic CNU-induced DNA lesion.

PMID- 9269991
TI  - Development of an adenovirus vector with tetracycline-regulatable human tumor
      necrosis factor alpha gene expression.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a multifunctional cytokine with direct
      antitumor activity. However, clinical trials using TNF-alpha for cancer treatment
      have been disappointing due in part to its severe side effects, and it has been
      estimated that TNF-alpha therapy would be effective only at 5-25 times the
      maximum tolerated dose. We have recently modified a tetracycline (Tc)
      repressor/operator-based mammalian gene expression system and have generated a Tc
      responsive recombinant adenovirus vector, AdVtTA.TNF-alpha. A variety of human
      tumor cells and T lymphocytes transduced by AdVtTA.TNF-alpha secreted high-titer
      (5,000-100,000 pg/10(6) cells/24 h) and biologically active TNF-alpha in the
      absence of Tc. Expression of TNF-alpha in the transduced cells was nondetectable
      when the culture medium contained as little as 0.1 microg/ml of Tc. At least a
      fraction of the clonogenic cells from human peripheral blood stem cell
      concentrates were also transducible by AdVtTA.TNF-alpha. The availability of this
      type of adenovirus vector opens a door to tumor- or organ-specific delivery of
      high-dose TNF-alpha and other therapeutic gene products for systemic cancer gene
      therapy.

PMID- 9269992
TI  - Epothilone B stabilizes microtubuli of macrophages like taxol without showing
      taxol-like endotoxin activity.
AB  - Epothilones are a new class of potential antitumor compounds that were isolated
      from the myxobacterium Sorangium cellulosum. Epothilones have effects on the
      cytoskeleton similar to those of the antineoplastic drug Taxol. Both compounds
      inhibit cell proliferation by stabilizing microtubuli, and they compete for the
      same binding site. In addition, Taxol displays endotoxin-like properties in that
      it activates macrophages to synthesize proinflammatory cytokines and nitric
      oxide. We measured nitric oxide release by IFN-gamma-treated murine macrophages
      as an indicator of macrophage activation by epothilone B. Although epothilone B
      showed the expected effects on the microtubuli, there was no indication of
      macrophage stimulatory activity by epothilone B, nor did epothilone B inhibit
      lipopolysaccharide-mediated nitric oxide release. We conclude that, unlike Taxol,
      epothilone-mediated microtubuli stabilization does not trigger endotoxin
      signaling pathways. Moreover, because the endotoxin-like activity of Taxol may be
      the cause of some nonhematological clinical side effects, it is to be expected
      that such effects may not occur with epothilones.

PMID- 9269993
TI  - Methylation of the BRCA1 gene in sporadic breast cancer.
AB  - Mutations of the BRCA1 gene in tumor DNA from patients with sporadic breast
      cancer have not yet been observed. Nevertheless, BRCA1 activity is markedly
      decreased in invasive breast tumors. Previous reports have shown that
      hypermethylation of the promoter region is an alternative mechanism to mutation
      for the inactivation of tumor suppressor genes. We examined the BRCA1 promoter
      region for hypermethylation by Southern blotting. Hypermethylation was observed
      in two of seven sporadic breast carcinomas but not in any normal tissues. The
      hypermethylation was not an artifact because a control region was unmethylated in
      the two tumors. Although not all tumors were hypermethylated, these observations
      are consistent with an important role for epigenetic mechanisms in human cancer.

PMID- 9269995
TI  - Loss of heterozygosity at 16q24.1-q24.2 is significantly associated with
      metastatic and aggressive behavior of prostate cancer.
AB  - Several studies have indicated that in prostate cancer, frequent aberrations take
      place in several genomic regions. In the present study, we have analyzed allelic
      losses in chromosome 16 region q in 50 prostate cancer specimens of various
      histological grades. The most frequently deleted region was located at 16q23
      16q24.2 between loci D16S504 and D16S422. The highest percentage of loss of
      heterozygosity (LOH) at 16q was also found within this area at loci HSD17B2 and
      D16S422 located at 16q24.1-q24.2. The LOH at 16q24.1-q24.2 was significantly
      associated with clinically aggressive behavior of the disease, metastatic
      disease, and higher tumor grade. Of the metastatic diseases, 83% showed LOH,
      whereas only 40% of the nonmetastatic diseases were found to show it. Similarly,
      LOH was found in 76% of the clinically aggressive diseases and in 33% of the
      nonaggressive diseases. The data suggest that a potentially important gene
      associated with prostate cancer progression is located close to 16q24.1-q24.2.

PMID- 9269994
TI  - A BRCA1 mutant alters G2-M cell cycle control in human mammary epithelial cells.
AB  - Mutations in BRCA1 increase the risk of breast and ovarian cancer. Although the
      mechanism by which mutant BRCA1 alters growth regulation is unknown, the COOH
      terminus of BRCA1 appears to play a critical role. To examine this, we introduced
      a vector expressing BRCA1 COOH-terminal residues 1293-1863 (CT-BRCA1) into
      nontumorigenic human breast epithelial cells. Overexpression of CT-BRCA1 led to a
      reduction in the doubling time (from 64 to 44 h) and a decreased reliance on
      growth factors, suggesting that this CT-BRCA1 may function in a dominant-negative
      manner. Expression of CT-BRCA1 induced alterations in cell cycle control, mainly
      in G2-M, including a loss of G2-M block by colchicine. These results suggest that
      one function of BRCA1-related growth control occurs by governing checkpoint(s)
      between DNA replication and mitosis.

PMID- 9269997
TI  - Nitric oxide induces conformational and functional modifications of wild-type p53
      tumor suppressor protein.
AB  - Incubation in vitro of recombinant wild-type murine p53 protein with S-nitroso-N
      acetyl-DL-penicillamine [a nitric oxide (NO)-releasing compound] has resulted in
      a change of p53 conformation and also in a significant decrease of its specific
      DNA binding activity. Similarly, upon treatment with S-nitroso-N-acetyl-DL
      penicillamine (2-5 mM) or S-nitroso-glutathione (1-2 mM), human breast cancer
      cells (MCF-7), which express wild-type p53, rapidly accumulated p53 protein in
      the nuclei. This p53 protein, however, possessed a significantly decreased
      activity of specific DNA binding. On the other hand, lower concentrations of NO
      donors (0.25-0.5 mM) stimulated p53 accumulation as well as its DNA binding
      activity. These results suggest that excess NO produced in inflamed tissues could
      play a role in carcinogenesis by impairing the tumor suppressor function of p53.

PMID- 9269996
TI  - Two- and three-dimensional cell structures govern epidermal growth factor
      survival function in human bladder carcinoma cell lines.
AB  - Human bladder carcinomas often express high levels of the epidermal growth factor
      (EGF) receptor. In three human bladder carcinoma cell lines (OBR, T24, and 647V),
      we show that two EGF receptor ligands, namely EGF and transforming growth factor
      alpha, enhanced the apoptosis due to serum starvation on cells cultured as
      monolayers. Conversely, EGF and transforming growth factor alpha prevented
      apoptosis when the same serum-starved cells were cultured as three-dimensional
      spheroids. Both stimulation and inhibition of apoptosis by EGF were associated
      with p21 WAF1/CIP1 overexpression. In 647V spheroids, EGF protection against
      radiation-induced apoptosis was negated by genistein and tyrphostin AG1478,
      suggesting that blockade of the EGF signal transduction in patients with bladder
      cancer may improve the radiotherapy efficacy.

PMID- 9269998
TI  - Association between CpG island methylation and microsatellite instability in
      colorectal cancer.
AB  - De novo methylation of promoter region CpG islands has been increasingly
      associated with transcriptional inactivation of important genes in neoplasia. To
      study the potential mechanisms underlying aberrant methylation in cancer, we have
      determined the methylation patterns of selected genes in colorectal cancers with
      and without microsatellite instability (MI), which results from defects in one of
      several base mismatch repair genes. A total of 47 colorectal cancers were
      analyzed, of which 15 were MI+ (32%). We now report that both the frequency and
      the extent of de novo methylation are strikingly increased in MI+ cancers.
      Hypermethylation of the p16 gene was found in 60% of MI+ cancers, compared to
      only 22% in MI- cancers (P = 0.02). Similarly, hypermethylation of the
      thrombospondin-1 (TSP-1) gene, an angiogenesis inhibitor, was increased in MI+
      cancers (27% versus 0%; P = 0.008). Extensive methylation of insulin-like growth
      factor II (IGF2) and hypermethylated in cancer-1 (HIC-1) genes was observed in 60
      and 80% of MI+ cancers, respectively, as contrasted with 6 and 38% of MI- cancers
      (P = 0.0002 and 0.01, respectively). Furthermore, 60% of the MI+ cancers
      displayed the hypermethylation events at two or more loci in a concordant manner
      compared to only 9% of the MI- cancers (P < 0.001). These results demonstrate a
      strong link between promoter hypermethylation and genetic instability due to
      deficient DNA repair.

PMID- 9270000
TI  - Prognostic role of the cyclin-dependent kinase inhibitor p27 in non-small cell
      lung cancer.
AB  - Despite its potential role as a tumor suppressor, p27 gene, a member of the
      Cip/Kip family of cyclin-dependent kinase inhibitor genes, has never been found
      mutated in human tumors. We investigated p27 protein expression in a series of
      108 non-small cell lung cancers (57.4% stage 1, 16.7% stage 2, and 25.9% stage 3)
      to determine whether the lack or altered expression of this protein correlates
      with neoplastic transformation and/or progression. We performed
      immunohistochemistry and Western blot analysis of each specimen. We found that
      tumors expressing low to undetectable levels of p27 contained high p27
      degradation activity. When we evaluated the outcome of the patients in
      relationship to p27 expression, we found p27 to be a prognostic factor
      correlating with the overall survival times (P = 0.0012). The possibility of a
      simple assay, such as the immunohistochemical analysis of p27 expression on
      routinely formalin-fixed, paraffin-embedded specimens, has considerable value for
      the prognosis of patients who undergo surgical resection. In addition,
      confirmation of the involvement of the proteasome-mediated proteolysis in p27
      degradation should stimulate new strategies of nonsurgical treatments of non
      small cell lung cancer.

PMID- 9269999
TI  - Cytotoxic synergy between flavopiridol (NSC 649890, L86-8275) and various
      antineoplastic agents: the importance of sequence of administration.
AB  - Flavopiridol, the first potent cyclin-dependent kinase inhibitor to undergo
      clinical trials as an antineoplastic agent in the United States, has attracted
      considerable attention because of its unique cellular targets and its ability to
      kill noncycling tumor cells in vitro. To better understand how flavopiridol might
      be used clinically, the present study used colony-forming assays to examine the
      cytotoxicity resulting from combining flavopiridol with eight other
      antineoplastic agents in four different administration schedules in A549 human
      non-small cell lung carcinoma cells in vitro. Cytotoxic synergy, as assessed by
      the median effect method, resulted when flavopiridol was combined with seven of
      the eight tested antineoplastic agents but was highly dependent upon
      administration schedule. Cisplatin was the only agent that resulted in sequence
      independent synergy when combined with flavopiridol. For paclitaxel, cytarabine,
      topotecan, doxorubicin, and etoposide, synergy was more pronounced when the
      agents were administered before flavopiridol rather than concomitant with or
      following flavopiridol. Examination suggested that this sequence dependence
      reflected arrest of cells in G1 and G2 phases of the cell cycle during and for 24
      h following flavopiridol treatment. Interestingly, 48-72 h after flavopiridol
      removal, the fraction of surviving cells in S phase increased 2-3-fold relative
      to untreated controls. Consistent with these results, administration of
      flavopiridol for 24 h followed 3 days later by exposure to an S phase-active
      agent (cytarabine or 5-fluorouracil) resulted in a highly synergistic
      interaction. These results highlight the importance of administration schedule
      when combining flavopiridol with other agents and provide a starting point for
      examining the effect of flavopiridol in drug combinations in vivo.

PMID- 9270001
TI  - Dissociation of radiation-induced phosphorylation of replication protein A from
      the S-phase checkpoint.
AB  - Replication protein A (RPA) is a trimeric single-stranded DNA-binding protein
      complex involved in DNA replication, repair, and recombination. DNA damage
      induces phosphorylation of the RPA p34 subunit, and it has been speculated that
      this phosphorylation could contribute to the regulation of the DNA damage-induced
      S-phase checkpoint. To further examine this potential relationship, human cell
      lines expressing ataxia telangiectasia (AT)-mutated dominant-negative fragments,
      which fail to arrest in S phase in response to ionizing radiation (IR), and AT
      cells expressing AT-mutated-complementing fragments, which regain the ability to
      arrest replicative DNA synthesis in response to IR, were analyzed for radiation
      induced RPA phosphorylation. Results from these studies demonstrate that IR
      induced RPA phosphorylation can be uncoupled from the S-phase checkpoint,
      suggesting that RPA phosphorylation in response to IR is neither necessary nor
      sufficient for an S-phase arrest.

PMID- 9270002
TI  - A p53-independent pathway for induction of p21waf1cip1 and concomitant G1 arrest
      in UV-irradiated human skin fibroblasts.
AB  - Largely on the basis of studies using the potent clastogen ionizing radiation, it
      has been widely assumed that up-regulation of the cyclin-dependent kinase
      inhibitor p21(waf1cip1) in cultured cells exposed to DNA-damaging agents is
      contingent upon the presence of functional p53 tumor suppressor protein.
      Nevertheless, we demonstrate here that the model mutagen 254-nm UV light induces
      p21(waf1cip1) protein and concomitant G1 arrest in normal human skin fibroblasts,
      as well as in p53-deficient fibroblasts derived from cancer-prone Li-Fraumeni
      syndrome patients. However, as expected, following exposure to ionizing
      radiation, elevated p21(waf1cip1) protein levels and G1 arrest were observed only
      in normal fibroblasts. These data provide a prominent and clinically relevant
      example in which p21(waf1cip1)-mediated growth arrest occurs independently of p53
      in human cells treated with a model DNA-damaging agent.

PMID- 9270003
TI  - Effect of the chimeric soluble granulocyte colony-stimulating factor receptor on
      the proliferation of leukemic blast cells from patients with acute myeloblastic
      leukemia.
AB  - The biological roles of the soluble granulocyte colony-stimulating factor (G-CSF)
      receptor, which arises as a result of alternative RNA splicing, are as yet
      unknown. In this study, we examined the in vitro effect of a chimeric protein
      composed of the extracellular region of a murine G-CSF receptor and the human
      IgG1 Fc region because a human natural soluble G-CSF receptor was not available.
      First, we found that this chimeric soluble G-CSF receptor could inhibit the
      biological activity of G-CSF on normal bone marrow colony formation. Because G
      CSF also plays an important role in the proliferation of leukemic blast cells, we
      next examined the effect of the soluble G-CSF receptor on leukemic blast colony
      formation in 10 acute myeloblastic leukemia cases. Although G-CSF stimulated the
      proliferation of leukemic progenitor cells to form leukemic blast colonies, the
      chimeric soluble G-CSF receptor completely inhibited this stimulatory effect.
      Furthermore, the chimeric soluble G-CSF receptor also inhibited spontaneous
      leukemic blast colony formation in two cases. Because a high concentration of G
      CSF was observed in the supernatants of leukemic blast cells from these two
      cases, it seems likely that the soluble G-CSF receptor cut off the autocrine
      growth mechanism of leukemic blast cells mediated by G-CSF. These findings
      suggest the possibility that the soluble G-CSF receptor could be used in a
      clinical application for acute myeloblastic leukemia patients in the future.

PMID- 9270004
TI  - The classification of benign and malignant human prostate tissue by multivariate
      analysis of 1H magnetic resonance spectra.
AB  - 1H magnetic resonance spectroscopy studies (360 MHz) were performed on specimens
      of benign (n = 66) and malignant (n = 21) human prostate tissue from 50 patients,
      and the spectral data were subjected to multivariate analysis, specifically
      linear-discriminant analysis. On the basis of histopathological assessments, an
      overall classification accuracy of 96.6% was achieved, with a sensitivity of 100%
      and a specificity of 95.5% in classifying benign prostatic hyperplasia from
      prostatic cancer. Resonances due to citrate, glutamate, and taurine were among
      the six spectral subregions identified by our algorithm as having diagnostic
      potential. Significantly higher levels of citrate were observed in glandular than
      in stromal benign prostatic hyperplasia (P < 0.05). This method shows excellent
      promise for the possibility of in vivo assessment of prostate tissue by magnetic
      resonance.

PMID- 9270005
TI  - CYP2D6 catalyzes tamoxifen 4-hydroxylation in human liver.
AB  - The major metabolites of tamoxifen (tam) formed by animal and human liver
      microsomes are mono-N-demethylated tam, 4-hydroxy-tam (4-OH-tam), and tam-N
      oxide. The N-desmethylated-tam and 4-OH-tam are formed by P450s, whereas the N
      oxide is primarily formed by flavin-containing monooxygenase. Because 4-OH-tam is
      a highly potent antiestrogen (and possibly is the active anticancer tam
      metabolite) and is on the path of formation of the reactive intermediate that
      binds covalently to proteins and DNA, it was of importance to identify the
      P450(s) catalyzing its formation. In the current study, three different
      preparations of expressed human P450s in Escherichia coli, lymphoblastoma cells,
      and insect cell line and livers from several human donors were used to identify
      the P450 isoform catalyzing the 4-hydroxylation (preliminary results were
      reported by Dehal et al., Eleventh International Symposium on Microsomes and Drug
      Oxidations, p. 71. Los Angeles, 1996). Tam metabolism was examined with human
      CYP2C8, 2C9, 2C18, 2C19, and 2D6 expressed in E. coli. These P450s were
      reconstituted with P450 reductase and lipid and were incubated with 50 microM
      [3H]tam and NADPH at 37 degrees C for 60 min. Essentially all of the recombinant
      P450s catalyzed the N-demethylation to various degrees; however, only 2D6 yielded
      detectable levels of 4-OH-tam. The inclusion of cytochrome b5 in the
      reconstituted system of 2D6 and 2C9 did not significantly affect the rate of 4
      hydroxylation, indicating that b5 is not essential for this activity. Tam
      metabolism by CYP1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2D6, 2E1, and 3A4, expressed in
      lymphoblastoma cells, revealed that only 2D6 significantly catalyzed the 4
      hydroxylation. Tam metabolism by CYP2D6 coexpressed with P450 reductase in a
      baculovirus infected insect cell line ("supersomes") exhibited marked tam 4
      hydroxylation. In an experiment with human liver microsomes, the inclusion of
      quinidine, a specific 2D6 inhibitor, resulted in approximately 50% inhibition of
      tam 4-hydroxylation without affecting N-demethylation. Polyclonal antibodies
      raised against 2D6 moderately inhibited (approximately 30%) the 4-hydroxylation
      in human liver microsomes. These results demonstrate a significant contribution
      by CYP2D6 to the catalysis of tam-4-hydroxylation by human liver.

PMID- 9270007
TI  - Pharmacokinetic analysis of 5-[18F]fluorouracil tissue concentrations measured
      with positron emission tomography in patients with liver metastases from
      colorectal adenocarcinoma.
AB  - The purpose of our study was to develop a pharmacokinetic model to quantify the
      intracellular 5-fluorouracil (5-FU) concentration in liver metastases, which is
      expected to be closely correlated to therapy response. In addition, the influence
      of the biomodulator folinic acid on the action of 5-FU in the metastases was
      investigated. After i.v. application of 5-FU labeled with the positron emitter
      fluorine-18 (5-[18F]FU), the kinetics of the regional 5-[18F]FU/uptake was
      measured dynamically with positron emission tomography over 120 min in 14
      patients with a total of 27 liver metastases from colorectal adenocarcinoma.
      Activity-time curves were evaluated in the metastases, the normal liver tissue,
      as well as in the aorta and analyzed by a six-compartment model. The catabolic
      breakdown of 5-FU to alpha-fluoro-beta-alanine (FBAL) in the normal liver tissue
      was modeled to separate the catabolites from the cytostatic agent 5-[18F]FU and
      the active 5-[18F]fluorodeoxyuridine nucleotides. With our model, all measured
      activity-time courses could be described adequately with only small
      interindividual variations in parameters connected with liver and blood.
      Extrahepatic clearance of 5-FU was estimated as 0.66 +/- 0.33 liters/min, whereas
      the hepatic clearance was 0.52 +/- 0.25 liters/min. The Michaelis-Menten
      parameters describing the nonlinear conversion of 5-FU to FBAL were Km = 11.3 +/-
      6.4 micromol and Vmax = 147.1 +/- 130.7 micromol/min. The maximum FBAL
      concentration in the liver was reached between 35 and 65 min after i.v. 5-FU
      infusion. The most sensitive parameters for therapy monitoring were k(in) and
      k(out), which characterize the transport in and out of the intracellular volume
      of the metastases, respectively. Tumor response can only be expected if k(in) is
      high and k(out) is low ("trapping"). These criteria were met by 6 of the 27
      metastases, which were identical to those with high values for the area under the
      intracellular 5-FU concentration curve (AUC[meta,IC]5-FU). The parameters k(in)
      and k(out) were also used to investigate the influence of the biomodulating agent
      folinic acid on drug effect. Five of the six metastases that showed trapping
      belonged to patients who received folinic acid. With the exception of one
      patient, however, all patients who received folinic acid had multiple metastases,
      of which only one was able to trap 5-FU. Because patient response can only be
      expected when all metastases trap 5-FU, folinic acid showed no effect on the
      overall clinical response. With the quantitative modeling approach used, trapping
      of 5-FU can be assessed noninvasively and on an individual basis. This makes it
      possible to adjust the dose for each individual patient to optimize the treatment
      schedule.

PMID- 9270006
TI  - Biochemical characterization of the protein activity responsible for high
      molecular weight DNA fragmentation during drug-induced apoptosis.
AB  - Cleavage of cellular DNA into high molecular weight (predominantly 50 kb)
      fragments is an early event during apoptosis. We previously reported that this
      fragmentation was a Ca2+-independent process during apoptosis, which was induced
      by anticancer agents in human leukemia cells. The present study demonstrated that
      a high molecular weight DNA fragmentation activity (HDFA) was induced in the drug
      treated cells and, upon fusion of the drug-treated cells with untreated target
      cells prelabeled with [14C]thymidine, caused fragmentation of the labeled DNA in
      the target cells. Furthermore, extracts of the drug-treated cells caused high
      molecular weight DNA fragmentation in nuclei isolated from untreated cells.
      Biochemical characterization of HDFA revealed the following properties: HDFA was
      proteinaceous in nature, as evidenced by its inactivation by heating or by
      digestion with proteinase K; HDFA required Mg2+ for optimal activity but was
      inhibited by Zn2+ and K+; HDFA was active in vitro at pH 6.0-8.0 and was inactive
      under more acidic conditions (pH < 6.0); addition of ATP (0.5-2 mM) substantially
      potentiated HDFA activity in isolated nuclei; and HDFA was not inhibited by actin
      (an inhibitor of DNase I) but was inhibited by the extracts from K562 cells,
      which were resistant to drug-induced apoptosis. The specific inhibitor of
      cysteine proteases (interleukin 1beta-converting enzyme protease family) blocked
      the generation of drug-induced high molecular weight DNA fragmentation in whole
      cells, whereas in isolated nuclei, the cysteine protease inhibitors did not
      prevent the cleavage of chromatin by exogenous HDFA. These results suggest that,
      once HDFA is activated during apoptosis, it does not require the presence of
      cysteine proteases for its endonucleolytic activity and that the cysteine
      proteases may be involved in the apoptotic process upstream of the activation of
      HDFA in whole cells.

PMID- 9270008
TI  - Cancer chemopreventive activity mediated by deguelin, a naturally occurring
      rotenoid.
AB  - Deguelin, a natural product isolated from Mundulea sericea (Leguminosae), was
      shown previously to mediate strong inhibition of 12-O-tetradecanoylphorbol-13
      acetate (TPA)-induced ornithine decarboxylase (ODC) activity in cell culture and
      to reduce the formation of preneoplastic lesions when mouse mammary glands were
      exposed to 7,12-dimethylbenz(a)anthracene. As reported currently, deguelin was
      synthesized and evaluated for chemopreventive activity in the two-stage 7,12
      dimethylbenz(a)anthracene/TPA skin carcinogenesis model with CD-1 mice and in the
      N-methylnitrosourea mammary carcinogenesis model with Sprague Dawley rats. In the
      mouse skin study, deguelin reduced tumor incidence from 60% in the control group
      to 10% in the group treated with a dose of 33 microg, and multiplicity was
      reduced from 4.2 in the control group to 0.1 in the treatment group. When the
      dose was increased 10-fold to 330 microg, no tumors were observed in the
      treatment group. These results correlated with the potential of deguelin to
      inhibit TPA-induced mouse epidermal ODC activity. When applied topically as a
      single dose in a time range of 2 h before to 2 h after TPA treatment, deguelin
      (384 microg) reduced ODC induction by TPA (6.17 microg) by more than 85%. Time
      course studies indicated that deguelin (33 microg) inhibited TPA (1.17 microg)
      induced ODC activity by 70% without affecting the kinetics of induction over a
      period of 10 h. Complete inhibition of ODC induction was observed at a dose of
      330 microg of deguelin. In the rat mammary tumorigenesis study, intragastric
      administration of 2 or 4 mg of deguelin/kg of body weight daily, 5 days/week,
      reduced tumor multiplicity from 6.8 tumors/rat in the control group to 5.1 or 3.2
      tumors/animal, respectively. At the 4 mg of deguelin/kg of body weight dose
      level, the tumor latency period was significantly increased. Tumor incidence,
      however, was unaffected. These data indicate that deguelin exhibits cancer
      chemopreventive effects in skin and mammary tumorigenesis models and that
      additional studies are warranted to characterize the cancer chemopreventive or
      chemotherapeutic potential of this substance more fully.

PMID- 9270009
TI  - Regulation of ornithine decarboxylase induction by deguelin, a natural product
      cancer chemopreventive agent.
AB  - Deguelin, a plant-derived rotenoid, mediates potent chemopreventive responses
      through transcriptional regulation of phorbol ester-induced ornithine
      decarboxylase (ODC) activity. To explore the mechanism of this effect, the
      activity of this compound was evaluated with a number of model systems. Using
      cultured mouse epidermal 308 cells, the steady-state levels of both 12-O
      tetradecanoylphorbol-13-acetate (TPA)-induced ODC mRNA and c-fos were decreased
      by treatment with deguelin. ODC activity was also inhibited by bullatacin and
      various antimitotic agents (podophyllotoxin, vinblastine, and colchicine), but
      only deguelin and bullatacin were active as inhibitors of ODC levels in a TPA
      independent c-Myc-mediated induction system using cultured BALB/c c-MycER cells.
      These results suggest that antimicrotubule effects, as mediated by rotenone, for
      example, are not responsible for inhibitory activity facilitated by deguelin.
      This was confirmed by use of an in vitro model of tubulin polymerization in which
      deguelin and a variety of other rotenoids were investigated and found to be
      inactive. As anticipated, however, NADH dehydrogenase was inhibited by these
      rotenoids. Moreover, inhibition of this enzyme correlated with a rapid depletion
      of ATP levels and potential to inhibit either TPA- or c-Myc-induced ODC activity.
      It therefore seems that deguelin-mediated interference with transient
      requirements for elevated energy can inhibit the induction of ODC activity and
      thereby yield a cancer chemopreventive response.

PMID- 9270010
TI  - Evidence that cutaneous carcinogen-initiated epithelial cells from mice are
      quiescent rather than actively cycling.
AB  - The basal layer of the epidermis and hair follicles is composed of actively
      cycling, transit-amplifying cells and quiescent cells including stem cells. To
      determine which population is the target of carcinogenic chemicals, we treated CD
      1 female mice topically with 5-fluorouracil (5-FU), an agent known to kill
      cycling but not quiescent cells, to probe the origin of the neoplastic lesions.
      We first determined that 5-FU kills cycling cells in the epidermis. Treatment of
      mice at 59 days of age (when in anagen 1) with topical 5-FU delayed hair regrowth
      by 10 days compared to vehicle-treated controls, suggesting that 5-FU killed the
      cells in anagen. Moreover, 5-FU suppressed the usual hyperplastic response of the
      epidermal cells to treatment with 12-O-tetradecanoylphorbol-13-acetate. 5-FU
      reduced the number of epidermal basal cells counted in cross-sections of skin and
      suppressed DNA synthesis. Approximately 50% of mice treated with 5-FU developed,
      within 1 week of treatment, a sloughing of the epidermis persisting for 3 weeks,
      followed by complete healing. Despite the evidence of cell killing in the
      epidermis and lower hair follicles, in a carcinogenesis experiment where 5-FU or
      vehicle was applied following tumor initiation with 7,12
      dimethylbenz[a]anthracene, the papilloma and carcinoma responses were virtually
      identical whether or not the mice were treated with 5-FU, suggesting that the
      tumors arose from quiescent, rather than actively cycling, epidermal cells. When
      5-FU was applied before initiation, the papilloma but not the carcinoma responses
      were slightly but significantly reduced relative to controls. These results are
      consistent with the hypothesis that the quiescent rather than the rapidly
      proliferating cells are the targets of tumor initiation.

PMID- 9270011
TI  - Retinyl methyl ether down-regulates activator protein 1 transcriptional
      activation in breast cancer cells.
AB  - Retinyl methyl ether (RME) is known to prevent the development of mammary cancer.
      However, the mechanism by which RME exerts its anticancer effect is presently
      unclear. The diverse biological functions of retinoids, the vitamin A
      derivatives, are mainly mediated by their nuclear receptors, retinoic acid
      receptors (RARs) and retinoid X receptors (RXRs). RARs and RXRs are ligand
      dependent transcriptional factors that either activate gene transcription through
      their binding to retinoic acid response elements or repress transactivation of
      genes containing the activator protein 1 (AP-1) binding site. Previous studies
      demonstrated that RME can modulate transcriptional activity of retinoid receptors
      on retinoic acid response elements, suggesting that regulation of retinoid
      receptor activity may mediate the anticancer effect of RME. In this study, we
      present evidence that RME can down-regulate AP-1 activity induced by the tumor
      promoter 12-O-tetradecanoylphorbol-13-acetate, insulin, growth factors, and the
      nuclear proto-oncogenes c-Jun and c-Fos. Transient transfection assays
      demonstrate that inhibition of AP-1 activity occurs on the human collagenase
      promoter containing an AP-1 binding site or the thymidine kinase promoter linked
      with an AP-1 binding site. In HeLa cells, the inhibition is observed when RAR
      alpha and/or RXR-alpha but not RAR-beta or RAR-gamma expression vectors are
      cotransfected, whereas the endogenous retinoid receptors in breast cancer cells T
      47D and ZR-75-1 were sufficient to confer the inhibition by RME. Furthermore,
      using gel retardation assay, we show that 12-O-tetradecanoylphorbol-13-acetate-
      and epidermal growth factor-induced AP-1 binding activity in breast cancer cells
      is inhibited by RME. These results suggest that one of the mechanisms by which
      RME prevents cancer development may be due to the repression of AP-1-responsive
      genes.

PMID- 9270012
TI  - Specific chromosomal changes in albumin simian virus 40 T antigen transgenic rat
      liver neoplasms.
AB  - Hepatocytes isolated from 3-month-old female rats bearing the albumin
      promoter/enhancer SV40 T antigen construct as a transgene demonstrated a 20%
      aneuploidy rate and a significant duplication of chromosome 1. Other chromosome
      changes were observed but were not statistically significant. At this time in the
      development of hepatic lesions, only a relatively small number of microscopic
      altered hepatic foci could be noted. By contrast, hepatocytes isolated from the
      age-matched nontransgenic controls demonstrated only 1% aneuploidy. One hundred %
      of the metaphase spreads isolated from hepatocellular neoplasms in transgenic
      rats were aneuploid. Although there were many random changes, 70% of the
      neoplastic cells demonstrated an amplification of all or portions of chromosome
      1q. Only 2% of the neoplastic cells had both a trisomy and a duplication. The
      smallest region of chromosome 1 that was duplicated was that between bands q3.7
      and q4.3. A loss of chromosome 3 was detected in 50% of the neoplasms, as well as
      a loss of chromosome 6 in 72% of the neoplastic cells. The carcinomas with the
      highest proliferation rate had also lost at least one copy of chromosome 15 in
      70% of the cells. The loss of chromosomes 3, 6, and 15 indicates that these
      regions may harbor one or more tumor suppressor genes. The amplification of a
      specific region of chromosome 1 is thus the first karyotypic alteration that can
      be identified in hepatocytes from livers from which hepatic neoplasms will arise.
      This indicates that expression or repression of one or more genes in this region
      may confer a growth advantage to preneoplastic hepatocytes, facilitating their
      transit to the neoplastic state in the stage of progression. Changes in
      chromosomes 3, 6, and 15 that occur subsequent to duplication of the q3.7-q4.3
      region of chromosome 1 are changes possibly reflecting alteration of tumor
      suppressor genes with further enhancement of neoplastic growth.

PMID- 9270013
TI  - Urinary excretion of unmetabolized and phase II conjugates of 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in
      humans: relationship to cytochrome P4501A2 and N-acetyltransferase activity.
AB  - Cooking meat, fish, or poultry at high temperature gives rise to heterocyclic
      aromatic amines (HAAs), which may be metabolically activated to mutagenic or
      carcinogenic intermediates. The enzymes cytochrome P4501A2 (CYP1A2) and N
      acetyltransferase (NAT2) are principally implicated in such biotransformations.
      We have determined the relationship between the activity of these two enzymes and
      the urinary excretion of unmetabolized and Phase II conjugates of the two HAAs
      MeIQx (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline) and PhIP (2-amino-1-methyl
      6-phenylimidazo[4,5-b]pyridine) in individuals fed a uniform diet containing high
      temperature cooked meat. The subjects in the study ate meat containing known
      amounts of MeIQx and PhIP, and urine collections were made 0-12 and 12-24 h after
      a meal. MeIQx and PhIP were measured in urine after acid treatment that
      quantitatively hydrolyzes the Phase II conjugates to the respective parent amine.
      The extracts containing the HAAs were purified by immunoaffinity chromatography
      and analyzed by liquid chromatography using electrospray ionization-tandem mass
      spectrometry. The MeIQx content in the 0-12 h urine increased after acid
      hydrolysis by a factor of 3-21-fold. After acid treatment, the total amount of
      MelQx (unmetabolized plus the N2-glucuronide and sulfamate metabolites) excreted
      in the 0-12 h urine was 10.5 +/- 3.5% (mean +/- SD) of the dose, whereas the
      total amount of PhIP [unmetabolized plus acid-labile conjugate(s)] in the 0-12 h
      period was 4.3 +/- 1.7% (mean +/- SD) of the dose. The total amount of PhIP in
      the 12-24 h urine after acid treatment was 0.9 +/- 0.4% (mean +/- SD) of the
      dose. Linear regression analysis of the amounts of MeIQx and PhIP excreted in the
      0-12 h period expressed as a percentage of the ingested dose, for all subjects,
      gave a low but significant correlation (r = 0.37, P = 0.005). Linear regression
      analyses showed that lower total MeIQx (unmetabolized plus the N2-glucuronide and
      sulfamate metabolites) in urine was associated with higher CYP1A2 activity,
      whereas total PhIP (unmetabolized plus conjugated) in urine showed no association
      to CYP1A2 activity. These results indicate that in humans, MeIQx metabolism and
      disposition are more strongly influenced by CYP1A2 activity than are those of
      PhIP. Linear regression analysis found no association between NAT2 activity and
      the levels (unmetabolized plus acid-labile conjugates) of MeIQx or PhIP excreted
      in urine.

PMID- 9270014
TI  - Dietary fat and colon cancer: modulation of cyclooxygenase-2 by types and amount
      of dietary fat during the postinitiation stage of colon carcinogenesis.
AB  - Several epidemiological and experimental studies have indicated a strong
      relationship between different types of dietary fats and risk of colon cancer.
      However, the modulating effects of these nutritional factors at the molecular
      level are not fully elucidated. It has been documented that the modulation of
      tumorigenesis is associated with changes in the levels of prostaglandins
      production. To provide an understanding of the mechanism(s) of dietary fat
      induced modulation of colon tumor development, we have analyzed the expression of
      cyclooxygenase (COX), an enzyme that catalyzes the metabolism of omega-3 and
      omega-6 polyunsaturated fatty acids in a critical step in prostaglandin
      biosynthesis. Male F344 rats were fed the semipurified AIN-76A diet containing
      low-fat corn oil and were s.c. injected azoxymethane (AOM) dissolved in normal
      saline at a dose rate of 15 mg/kg of body weight, once weekly, for 2 weeks.
      Vehicle controls received s.c. equal volumes of normal saline. One day after the
      second AOM or saline injection, rats intended to receive experimental diets were
      provided high-fat corn oil (HFCO) or high-fat fish oil (HFFO) mixed in
      semipurified AIN-76A diet, and the remaining rats continued to receive the low
      fat corn oil diet. Animals were sacrificed 1, 12, or 36 weeks after the last AOM
      or saline injection, and their colonic mucosa, as well as the grossly visible
      colon tumors from rats sacrificed 36 weeks after the last AOM injection, were
      analyzed for the expression levels of COX-1 and COX-2. The results indicate that
      AOM induced increasingly high levels of COX-2 expression with advancing stages of
      colon tumorigenesis. HFCO further enhanced the AOM-induced COX-2 expression. In
      contrast, HFFO ingestion resulted in a significant decrease in COX-2 expression
      both in the colonic mucosa and in tumors. These results correlate with increased
      incidence and multiplicity of grossly visible colon tumors in AOM-treated animals
      that were fed the HFCO diet versus decreased tumor incidence and lower tumor
      multiplicity in animals that were fed the HFFO diet. No significant differences
      were observed in expression levels of COX-1. The data suggest that HFCO may
      promote colon tumorigenesis by up-regulating the COX-2 expression, whereas HFFO
      may exert its antitumor effect by inhibiting the COX-2 expression.

PMID- 9270015
TI  - p53 mutations, chronic hepatitis B virus infection, and aflatoxin exposure in
      hepatocellular carcinoma in Taiwan.
AB  - Recent studies have implicated aflatoxin B1 (AFB1) exposure as an etiological
      agent in hepatocellular carcinoma (HCC) and suggested an interaction with chronic
      hepatitis B virus (HBV) infection. Worldwide AFB1 exposure correlates with a
      specific mutation at codon 249 in the p53 tumor suppressor gene in liver tumors.
      This study investigated the roles of HBV and AFB1 in the HCC carcinogenic pathway
      involving p53 mutations. In cases and controls, chronic HBV infection was
      assessed by serum hepatitis B surface antigen (HBsAg) and AFB1 exposure by
      immunohistochemical detection of AFB1-DNA adduct in liver tissue. p53 protein
      mutations in tumor tissues of HCC cases were identified by immunohistochemistry
      and DNA mutations by single-stranded conformational polymorphism and sequencing
      analysis. Both chronic HBsAg carrier status and liver AFB1-DNA adducts were
      significantly higher in cases than in controls with odds ratios (OR) of 8.4 and
      3.9, respectively (P < 0.01). Moreover, HCC risk was greatest in individuals with
      both AFB1-DNA adducts and HBsAg, suggesting a viral-chemical interaction. Mutant
      p53 protein, mutations in the p53 gene, and specific codon 249 mutations were
      detected in 37, 29, and 13%, respectively, of the HCC cases. Most of the DNA
      mutations were transversions, and the only major clustering site for mutations
      was codon 249. AFB1-DNA adducts were associated with p53 protein (OR = 2.9, P =
      0.054) and DNA mutations (OR = 2.9, P = 0.082) but with borderline significance.
      All of the codon 249 mutations (n = 12) occurred in HBsAg-seropositive carriers,
      resulting in an OR of 10.0 (P < 0.05), suggesting that HBV may be involved in the
      selection of these mutations. The ORs between HBsAg and p53 DNA and protein
      mutations were 2.6 (P = 0.077) and 1.8 (P > 0.05), respectively. Both p53 DNA and
      protein mutations were related to tumor stage, suggesting that they are late
      events. These studies provided further support for the role of aflatoxin exposure
      in HCC in Taiwan and insight into viral-chemical interactions and molecular
      pathogenesis.

PMID- 9270016
TI  - A functional assay in yeast for the human estrogen receptor displays wild-type
      and variant estrogen receptor messenger RNAs present in breast carcinoma.
AB  - Human estrogen receptor (hER) variants or mutants with altered functional
      activity may be responsible for resistance to the antiestrogen tamoxifen in
      breast cancer. The method presented in this report is a screening method for
      functional activity of hER in yeast Saccharomyces cerevisiae. hER mRNA isolated
      from breast cancer tissue is subjected to reverse transcription-PCR, directly
      cloned into a yeast expression vector in vivo, and subsequently tested for
      functional activity in a simple yeast growth assay. This technique, functional
      analysis of separated alleles in yeast of the human estrogen receptor (hER
      FASAY), gives a display of the prevalence and functional activity of all of the
      variant hER mRNAs among normal, wild-type receptors in a breast tumor sample. The
      hER-FASAY can discriminate among wild-type hER, constitutively active hER, and
      inactive hER. In contrast to standard immunohistochemistry, this assay gives
      insight into the functional activity of hER. The hER-FASAY was optimized and
      validated using breast cancer cell lines MCF-7 and T47D and seven breast cancer
      biopsies. Phenotypes detected with the hER-FASAY were validated by DNA
      sequencing. In both cell lines and tumor biopsies, hER variants are highly common
      and mainly caused by alternative RNA splicing, whereas point mutations and
      deletions occur only at low frequency.

PMID- 9270017
TI  - MCF7/LCC9: an antiestrogen-resistant MCF-7 variant in which acquired resistance
      to the steroidal antiestrogen ICI 182,780 confers an early cross-resistance to
      the nonsteroidal antiestrogen tamoxifen.
AB  - Acquired resistance to antiestrogens is a major problem in the clinical
      management of initially endocrine responsive metastatic breast cancer. We have
      shown previously that estrogen-independent and -responsive MCF7/LCC1 human breast
      cancer cells selected for resistance to the triphenylethylene tamoxifen produce a
      variant (MCF7/LCC2) that retains sensitivity to the steroidal antiestrogen ICI
      182,780 (N. Brunner et al., Cancer Res., 53: 3229-3232, 1993). We have now
      applied stepwise selections in vitro from 10 pM to 1 microM ICI 182,780 against
      MCF7/LCC1 and obtained a stable ICI 182,780-resistant variant designated
      MCF7/LCC9. In contrast to 4-hydroxytamoxifen-selected MCF7/LCC2 cells, MCF7/LCC9
      cells exhibit full cross-resistance to tamoxifen, despite never having been
      exposed to this drug. Significantly, tamoxifen cross-resistance arose early in
      the selection, appearing following selection against only 0.1 nM ICI 182,780.
      Although limited resistance to ICI 182,780 also was observed, full ICI 182,780
      resistance was not detected until the selective pressure increased to 100 nM ICI
      182,780. Cross-resistance to tamoxifen persisted throughout these additional
      selections. Despite their antiestrogen cross-resistance, MCF7/LCC9 cells retain a
      level of estrogen receptor expression comparable to that of their parental
      MCF7/LCC1 cells. Whereas MCF7/LCC1 cells retain an estrogen-inducible expression
      of progesterone receptors, MCF7/LCC9 cells exhibit an up-regulated expression of
      both progesterone receptor mRNA and protein that is no longer estrogen
      responsive. Estrogen-independent and -responsive components of the MCF7/LCC9
      phenotype are apparent in vivo. These cells form slowly growing tumors in
      ovariectomized athymic nude mice but respond mitogenically upon estrogenic
      supplementation. The in vivo growth of MCF7/LCC9 tumors is not affected by
      treatment with ICI 182,780. Although there is some evidence of tamoxifen
      stimulation of tumor growth, this did not reach statistical significance. If this
      pattern of cross-resistance occurs in some breast cancer patients, administering
      triphenylethylene antiestrogens as a first-line therapy with a cross-over to
      steroidal compounds upon recurrence may be advantageous.

PMID- 9270018
TI  - Blockade of the stimulatory effect of estrogens, OH-tamoxifen, OH-toremifene,
      droloxifene, and raloxifene on alkaline phosphatase activity by the antiestrogen
      EM-800 in human endometrial adenocarcinoma Ishikawa cells.
AB  - Although temporary benefits of tamoxifen therapy are observed in up to 40% of
      women with breast cancer, this compound, which is known to possess mixed
      estrogenic and antiestrogenic activities, has been associated with increased risk
      of endometrial carcinoma. This study compares the effects of the novel
      nonsteroidal pure antiestrogen EM-800 and related compounds with those of a
      series of antiestrogens on the estrogen-sensitive alkaline phosphatase (AP)
      activity in human endometrial adenocarcinoma Ishikawa cells. Exposure to
      increasing concentrations of up to 1000 nM EM-800 or its active metabolite EM-652
      alone failed to affect basal AP activity. In contrast, incubation with 10 nM (Z)
      4-OH-tamoxifen, (Z)-4-OH-toremifene, droloxifene, or raloxifene increased the
      value of this estrogen-sensitive parameter by 3.3-, 3.5-, 2.2-, and 1.6-fold,
      respectively, a stimulatory effect that was completely reversed by simultaneous
      exposure to 30 nM EM-800. Moreover, the stimulation of AP activity induced by 1
      nM 17beta-estradiol was completely reversed by EM-800, EM-652, or ICI-182780, at
      the IC50 value of 1.98 +/- 0.23, 1.01 +/- 0.16, and 5.64 +/- 0.59 nM,
      respectively, whereas the partial blockade exerted by (Z)-4-OH-tamoxifen, (Z)-4
      OH-toremifene, or raloxifene was observed at IC50 values of 13.5 +/- 3.80, 41.0
      +/- 7.2, and 3.74 +/- 0.43 nM, respectively. Thus, as assessed by their activity
      in the human Ishikawa endometrial carcinoma cells, EM-800 and EM-652 are the most
      potent known antiestrogens in Ishikawa cells, and, most importantly, they are
      devoid of the estrogenic activity observed in these human endometrial cancer
      cells with (Z)-4-OH-tamoxifen, (Z)-4-OH-toremifene, droloxifene, and raloxifene.

PMID- 9270019
TI  - Regulation of proliferation and Ras localization in transformed cells by products
      of mevalonate metabolism.
AB  - Lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl (HMG) CoA reductase, and 6
      fluoromevalonate (Fmev), an inhibitor of diphosphomevalonate decarboxylase,
      blocked the synthesis of downstream mevalonate products, including prenyl-derived
      lipids, and prevented membrane localization of Ras in the myeloid cell line U
      937. In contrast to lovastatin, which induced cytosol localization of Ras in U
      937 cells, Fmev failed to increase cytosolic Ras and also completely prevented
      the proliferation of U-937 cells. Growth of U-937 cells was restored by the
      addition of lovastatin to Fmev-blocked cells. These results implied that a
      product of mevalonate metabolism proximal to isopentenyl diphosphate was
      responsible for the suppression of proliferation. To delineate the action of this
      endogenous inhibitor of cell proliferation and determine the relationship between
      its impact on Ras localization and cell proliferation, the effect of Fmev on a
      variety of leukemia- and lymphoma-derived cells was examined. Whereas Fmev
      blocked the growth of these cell lines, there were more than 50-fold differences
      in the concentrations required to inhibit the growth of individual cell lines by
      90%. Regardless of its effect on cell proliferation, the biochemical effect of
      Fmev was similar. Thus, Fmev uniformly prevented the conversion of radiolabeled
      mevalonate to isopentenyl diphosphate and other downstream products, including
      synthesis of sterol and nonsterol lipids and prenylation of proteins. A
      correlation was noted between higher intrinsic rates of mevalonate synthesis by a
      cell and susceptibility to inhibition by Fmev. Thus, sensitivity of a cell line
      to inhibition by Fmev was associated with markedly increased rates of HMG CoA
      reductase activity that were further increased by incubation with Fmev. Whereas
      Fmev depleted cellular levels of the prenylated protein Ras in the sensitive cell
      line U-937, there was no depletion of cellular Ras levels in the resistant cell
      line EL-4, but rather, there was a shift of Ras from membrane to cytosol, as
      expected for inhibition of prenylation. These results suggest that leukemic cells
      with increased HMG CoA reductase activity produce increased levels of an
      endogenous mevalonate-derived inhibitor that leads to Ras depletion and
      suppression of cell growth. As a result, inhibition of the growth of these
      transformed cells might be specifically accomplished by Fmev.

PMID- 9270020
TI  - Methotrexate is excreted into the bile by canalicular multispecific organic anion
      transporter in rats.
AB  - Methotrexate [(+) amethopterin, L-MTX] has two carboxyl groups in its structure
      and is eliminated mainly by excretion into urine and bile. To investigate the
      biliary excretion mechanism of L-MTX, we performed in vivo and in vitro studies
      using mutant rats, Eisai hyperbilirubinemic rats (EHBRs), whose canalicular
      multispecific organic anion transporter (cMOAT) is defective as a consequence of
      heredity. After i.v. administration of L-MTX to EHBRs, its plasma disappearance
      and biliary excretion was slower than in normal Sprague Dawley rat (SDR). ATP
      dependence and overshoot phenomena were observed in the uptake of [3H]L-MTX by
      canalicular membrane vesicles (CMV) prepared from SDR, whereas no ATP-dependence
      was observed in CMV from EHBRs. The ATP-dependent uptake of L-MTX by SDR CMV
      exhibited saturable kinetics with a Km of 295 microM. L-MTX competitively
      inhibited the ATP-dependent uptake of [3H]2,4-dinitrophenyl-S-glutathione, a
      typical substrate for cMOAT, and the inhibition constant (Ki) of L-MTX was
      comparable with its own Km. These results suggest that L-MTX is excreted into
      bile by cMOAT. The inhibitory effects of L-MTX and its optical isomer, (-)
      amethopterin (D-MTX), on the uptake of [3H]L-MTX differed with Kis of 326 and 93
      microM, respectively, indicating that the biologically inactive D form has a
      higher affinity for cMOAT than L-MTX.

PMID- 9270022
TI  - T-cell receptor zeta-chain expression on tumor-infiltrating lymphocytes from
      renal cell carcinoma.
AB  - Loss of the T-cell receptor-associated zeta chain in tumor-infiltrating
      lymphocytes (TILs) has been proposed as one mechanism of acquired
      immunosuppression in cancer patients. Recent reports suggest that zeta-chain loss
      may be related to contaminating monocyte/macrophage protease activity. Using flow
      cytometry and Western blot analysis, we have confirmed the expression of zeta
      chain in matched peripheral blood mononuclear cells and TILs from eight patients
      with primary renal cell carcinoma, when the cells were exposed to sufficient
      quantity of protease inhibitors. A small decrease in zeta-chain expression was
      found in three TIL samples. The loss of zeta-chain expression that was noted by
      others may be related to differences in laboratory method, and the small changes
      we have noted are unlikely to be sufficient in explaining the immunosuppression
      of TILs.

PMID- 9270021
TI  - Antitumor activity and immunotherapeutic properties of Flt3-ligand in a murine
      breast cancer model.
AB  - Flt3-Ligand (Flt3-L) is a stimulatory cytokine for a variety of hematopoietic
      lineages, including dendritic cells and B cells. The antitumor properties of Flt3
      L were evaluated in C3H/HeN mice challenged with the syngeneic C3L5 murine breast
      cancer cell line. Eighty % of animals receiving 500 microg/kg/day of Chinese
      hamster ovary-derived human Flt3-L for 10 days were protected from tumor growth,
      whether the tumor challenge was administered on the first or fourth days of Flt3
      L administration. The protection provided by soluble Flt3-L was transient. All
      tumor-free animals rechallenged 4 weeks after the primary challenge developed
      tumor. Transduction of C3L5 with retroviral vectors expressing human or murine
      Flt3-L did not influence in vitro growth or MHC expression but decreased in vivo
      tumor development to 0 and 10% of mice, respectively. This compares with tumor
      growth of 52% with interleukin-2 transduced C3L5 and over 85% with untransduced
      and control vector-transduced C3L5. Unlike animals treated with soluble Flt3-L,
      administration of Flt3-L as a tumor vaccine protected mice from a subsequent
      challenge with untransduced C3L5 in 60-78% of mice, compared to 0% of controls.
      Our initial work used the most common Flt3-L isoform, which is membrane bound but
      can undergo proteolytic cleavage to generate a soluble form. To evaluate the role
      of the various Flt3-L isoforms in preventing tumor formation, retroviral vectors
      encoding only the membrane-bound form or only the soluble isoform were evaluated
      in the C3L5 model. Tumor formation was similar with either isoform, preventing
      tumor formation in 80-90% of mice after the primary challenge and 88-89% after
      the secondary challenge. Splenocytes obtained 4 weeks after the secondary
      challenge conferred adoptive immunity to naive mice in 60% of animals. This
      initial report of antitumor activity by Flt3-L is consistent with its known
      stimulatory effect on antigen-presenting cells and suggests it may enhance the
      development of tumor vaccines.

PMID- 9270023
TI  - Loss of heterozygosity analysis in primary mammary tumors and lung metastases of
      MMTV-MTAg and MMTV-neu transgenic mice.
AB  - Loss of heterozygosity (LOH) analysis has been used in many types of human cancer
      to localize putative tumor suppressor genes important in carcinogenesis. However,
      this approach has only recently been applied to transgenic mouse tumor models,
      which offer greater opportunity for detailed molecular genetic analysis of tumor
      initiation and progression. To explore the possible role of secondary genetic
      events in transgenic mouse mammary tumor development, we performed microsatellite
      based allelotypes on primary mammary adenocarcinomas and lung metastases arising
      in mice transgenic for the polyomavirus middle T antigen under the control of the
      mouse mammary tumor virus promoter/enhancer (MMTV-MTAg mice) and on primary
      mammary adenocarcinomas arising in mice transgenic for the neu proto-oncogene
      (MMTV-neu mice). We examined a total of 80 microsatellite loci distributed
      throughout the mouse genome for LOH and observed high rates of specific
      chromosomal loss but very low rates of background allelic loss in these tumors.
      For the MMTV-MTAg mice, no individual chromosomes showed rates of LOH
      significantly above the background rates. For MMTV-neu mice, markers on
      chromosome 4 showed LOH in 82% of mammary tumors, whereas markers on chromosome 3
      showed loss in 29% of tumors. These data suggest that the middle T antigen
      transgenic mice do not undergo whole chromosome loss or large genomic deletions
      as common mechanisms of tumor formation and that chromosomes 3 and 4 may contain
      tumor suppressor gene loci that play important roles in the development of neu
      mediated mouse mammary tumors.

PMID- 9270024
TI  - Expression of neurogenic basic helix-loop-helix genes in primitive
      neuroectodermal tumors.
AB  - The basic helix-loop-helix (bHLH) class of transcription factors plays a pivotal
      role in tissue-specific determination and differentiation. Moreover, dysregulated
      expression or loss of function of these factors contributes to leukemogenesis and
      solid tumor development. Neurogenesis is regulated by genes of the NEUROD/atonal
      and ACHAETE SCUTE families. We analyzed expression of human NEUROD1, NEUROD2,
      NEUROD3, and ACHAETE SCUTE 1 (HASH1) in cerebellar and cerebral primitive
      neuroectodermal tumors (PNETs), gliomas, and cell lines derived from a variety of
      neuroectodermal tumors by Northern analysis and in situ hybridization. NEUROD1
      was expressed in each of the 12 medulloblastoma specimens, whereas NEUROD2 and
      NEUROD3/neurogenin were expressed in partly overlapping subsets of
      medulloblastomas. All of the tumors that presented with distant metastases
      expressed NEUROD3. The only other NEUROD3-positive tumor progressed early in
      treatment. Human ACHAETE SCUTE homologue (HASH1) was not expressed in
      medulloblastomas (infratentorial PNETs) but was expressed in three of five
      supratentorial PNETs. Neuroectodermal tumor cell lines derived from other sites
      (e.g., neuroblastoma and retinoblastoma) expressed NeuroD and ACHAETE SCUTE
      family members. No NEUROD message was detected in glial tumors or cell lines.
      Neurogenic bHLH transcription factor expression patterns suggest that specific
      family members may contribute to or reflect biological differences that arise
      during malignant transformation.

PMID- 9270025
TI  - Neurofilament heavy chain-like messenger RNA and protein are present in benign
      prostate and down-regulated in prostatic carcinoma.
AB  - Differences in gene expression between benign and malignant human prostate
      specimens were investigated using the differential display technique. RNA samples
      from paired benign and malignant areas microdissected from opposite sides of the
      same prostate gland were used for reverse transcription PCR. A 477-bp band was
      identified that was consistently present in benign prostate but absent or
      diminished in intensity in malignant tissue. This band was cloned, and the
      sequence demonstrated 99% identity with a region in the fourth exon of the human
      neurofilament heavy chain gene (NF-H). Northern blotting with a cDNA probe
      derived from this band confirmed the presence of a similarly sized message of
      approximately 3.9 kb in both prostate and brain, and reverse transcription PCR
      using primers specific to an upstream region of exon 4 confirmed NF-H-like mRNA
      expression in benign prostatic tissue. Immunostaining with a monoclonal antibody
      to NF-H showed a positive reaction in benign prostatic epithelial cells but
      complete absence of staining in prostatic cancer cells. These data demonstrate
      the presence of a NF-H-like gene product in normal prostatic epithelial cells
      that is down-regulated or absent in prostatic carcinomas.

PMID- 9270026
TI  - Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues of the
      multidrug resistance-associated protein gene (MRP1), in human cancer cell lines.
AB  - By screening databases of human expressed sequence tags, we have identified three
      new homologues of MRP1, the gene encoding the multidrug resistance-associated
      protein, and cMOAT (or MRP2), the canalicular multispecific organic anion
      transporter gene. We call these new genes MRP3, MRP4, and MRP5. MRP3, like cMOAT,
      is mainly expressed in the liver. MRP4 is expressed only at very low levels in a
      few tissues, and MRP5, like MRP1, is expressed in almost every tissue tested. To
      assess a possible role of these new MRP homologues in multidrug or cisplatin
      resistance, a large set of resistant cell lines was examined for the
      (over)expression of MRP1, cMOAT, MRP3, MRP4, and MRP5. We find that even in cells
      selected for a low level of resistance, several MRP-related genes can be up
      regulated simultaneously. However, MRP4 is not overexpressed in any of the cell
      lines we analyzed; MRP3 and MRP5 are only overexpressed in a few cell lines, and
      the RNA levels do not seem to correlate with resistance to either doxorubicin or
      cisplatin. cMOAT is substantially overexpressed in several cell lines, and cMOAT
      RNA levels correlate with cisplatin but not doxorubicin resistance in a subset of
      resistant cell lines. Our results emphasize the need for gene-specific blocks in
      gene expression to define which transporter contributes to resistance in each
      resistant cell line.

PMID- 9270027
TI  - Isolation of a candidate gene, CAB1, for cholesterol transport to mitochondria
      from the c-ERBB-2 amplicon by a modified cDNA selection method.
AB  - An improved cDNA selection method was established to isolate expressed genes
      efficiently from an amplified chromosome region in human cancer. Biotinylated
      yeast artificial chromosome DNA containing c-ERBB-2 was hybridized in solution
      with PCR-amplifiable cDNAs of an esophageal cancer cell line bearing the c-ERBB-2
      amplification. After capturing the hybrids on avidin-coated magnetic beads, the
      cDNAs were amplified by PCR. Four new genes (A39, C51, CAB1, and GRB-7)
      coamplified with c-ERBB-2 were isolated from the enriched cDNA library. CAB1, GRB
      7, and c-ERBB-2 were overexpressed in gastric and esophageal cancer cells in
      correspondence with the amplification. The deduced amino acid sequence of the
      CAB1 gene had significant homology to the recently discovered steroidogenic acute
      regulatory protein, StAR, which plays an essential role in cholesterol transport
      to mitochondria. It was established that multiple overexpressed genes are
      frequently present in a single amplicon.

PMID- 9270028
TI  - RNA fingerprinting displays UVB-specific disruption of transcriptional control in
      human melanocytes.
AB  - In mammalian cells, UV induces a limited set of early transcribed genes, which
      overlaps with the set of genes induced by tumor promoting drugs such as 12-O
      tetradecanoyl phorbol-13-acetate (TPA). Among these are genes for transcription
      factors, the activation of which leads to complex secondary changes in expression
      of multiple target genes. How these delayed pleiotropic UV effects on
      transcription may contribute to initiation of melanoma skin cancer is poorly
      understood. We analyzed changes in the relative abundances of 1900 transcripts in
      newborn human melanocytes 8 h after treatment with UVB, TPA, and cycloheximide in
      all combinations, using RNA arbitrarily primed PCR for differential display. The
      relative abundances of 205 transcripts (11% of all transcripts surveyed) were
      altered by one or more of the treatment combinations. Fourteen of the 77 genes up
      regulated by TPA were also up-regulated by UVB, but 60 of the TPA up-regulated
      genes were down-regulated by UVB, indicating both intersecting and independent
      signal transduction pathways for UVB and TPA. A number of UVB and TPA target
      genes were identified by cDNA cloning. Consistent with UVB induction of a partly
      transformed phenotype in mammalian cells, UVB antagonized the TPA-inducible
      expression of tumor-suppressive tropomyosin 3 mRNA. In addition, UVB may impair
      mitochondrial functioning and induce oxidative stress by strong down-regulation
      of mitochondrial transcription. Finally, increased expression of the
      dihydropteridine reductase gene, a major regulator of the cellular
      tetrahydrobiopterin pool, was linked to the UV pathway.

PMID- 9270029
TI  - Translational enhancement of mdm2 oncogene expression in human tumor cells
      containing a stabilized wild-type p53 protein.
AB  - The mdm2 oncogene has transforming potential that is activated by overexpression.
      We previously reported the identification of human choriocarcinoma cell lines
      that have very high levels of mdm2 proteins as well as elevated levels of a
      stabilized wild-type p53 protein. Importantly, this mdm2 overexpression resulted
      from enhanced translation of mdm2 mRNA, a mechanism that had not previously been
      implicated in mdm2 expression control. The focus of this study was to investigate
      the breadth of enhanced translation of mdm2 mRNA in human cancers and to
      elucidate the basis for this translational activation. Here we present evidence
      that translational enhancement of mdm2 expression occurs in a variety of human
      tumor cells. Most of these samples also have high levels of wild-type p53
      protein. However, there is no evidence for concomitant overexpression of the p53
      target genes p21/waf1 and gadd45. Additionally, we demonstrate that the
      translational enhancement of mdm2 involves a preferential increase in mdm2
      transcription that is initiated from the internal p53-responsive promoter region
      of this gene. The particular mdm2 transcripts that are generated contain a
      distinct 5' untranslated region and exhibit a significantly enhanced
      translational efficiency. These data provide a quantitative explanation for the
      overexpression of mdm2 proteins in this class of human tumors.

PMID- 9270030
TI  - Inhibitors of both nuclear factor-kappaB and activator protein-1 activation block
      the neoplastic transformation response.
AB  - Cross-coupling of active protein-1 (AP-1) and nuclear factor (NF)-kappaB has been
      reported. In the present study, we investigated the possibility that both of
      these two transcription factors might contribute to the process of tumor promoter
      induced transformation. To establish a stable reporter cell system, two reporter
      genes were stably transfected into a JB6 mouse tumor promotion-sensitive (P+)
      cell line: a luciferase reporter controlled by a collagenase AP-1 sequence and a
      chloramphenicol acetyltransferase reporter controlled by an interleukin 6 NF
      kappaB sequence. This double-reporter cell line maintained the phenotype of tumor
      promotion sensitivity and was able to report basal or induced AP-1 and NF-kappaB
      transactivation. The cytokine tumor promoter tumor necrosis factor (TNF)-alpha
      transactivated NF-kappaB and AP-1 for both DNA binding and transcriptional
      activity. Pyrrolidine dithiocarbamate, an antioxidant that acts as an NF-kappaB
      inhibitor, efficiently inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA) or
      TNF-alpha induced NF-kappaB as well as AP-1 transactivation and cell
      transformation, suggesting dependency of transformation on both transcription
      factors. The AP-1 transrepressing-retinoid SR11302 transrepressed AP-1 and cell
      transformation when these were TPA induced but not when TNF-alpha induced,
      indicating different signaling pathways for TNF-alpha and TPA. Supershift
      electrophoresis mobility shift assay revealed that Jun B and c-Jun were absent
      from the AP-1/DNA complex following TNF-alpha but present following TPA
      treatment. Together, these results suggest that both AP-1 and NF-kappaB
      activation may be required for transformation whether induced by TPA or by TNF,
      and the differential sensitivity of TPA and TNF-alpha-induced transformation to
      inhibition by a retinoid might be explained by differences in the composition of
      the DNA-bound AP-1 complexes.

PMID- 9270031
TI  - Purification and characterization of human lung fibroblast motility-stimulating
      factor for human soft tissue sarcoma cells: identification as an NH2-terminal
      fragment of human fibronectin.
AB  - Paracrine motogenic factors, including motility cytokines and extracellular
      matrix molecules secreted by normal cells, can stimulate metastatic cell
      invasion. Both intact extracellular matrix molecules and their degradative
      products may exhibit these activities. We have found that human lung fibroblasts
      produce paracrine motility-stimulating factors for recently established human
      sarcoma cell strains. We purified the major fibroblast motility-stimulating
      factor (FMSF) from human lung fibroblast-conditioned medium by sequential heparin
      affinity chromatography and DEAE anion exchange chromatography.
      Lysylendopeptidase C digestion of FMSF and sequencing of peptides purified by
      reverse-phase high-pressure liquid chromatography identified FMSF as an NH2
      terminal fragment of human fibronectin. Using SYN-1 sarcoma cells, FMSF
      predominantly stimulated chemotaxis and some chemokinesis, and it was chemotactic
      for a variety of human sarcoma cells, including fibrosarcoma, leiomyosarcoma,
      liposarcoma, synovial sarcoma, and neurofibrosarcoma cells. The FMSF activity
      present in human lung fibroblast-conditioned medium was completely eliminated by
      either neutralization or immunodepletion with a rabbit antihuman-fibronectin
      antibody, thus further confirming that the NH2-terminal fibronectin fragment was
      the FMSF responsible for the motility stimulation of human soft tissue sarcoma
      cells. Because human soft tissue sarcomas have a distinctive hematogenous
      metastatic pattern (predominantly lung), and lung-derived fibroblasts secrete
      large amounts of FMSF, FMSF and fibronectin may play a role in stimulating
      sarcoma invasion into lung tissue.

PMID- 9270032
TI  - Prevention of breast cancer growth, invasion, and metastasis by antiestrogen
      tamoxifen alone or in combination with urokinase inhibitor B-428.
AB  - Urokinase (urokinase plasminogen activator, uPA) and its cell surface receptor
      (uPA receptor, uPAR) play an important role in a variety of physiological and
      pathological processes requiring cell migration and tissue remodeling. Using our
      syngeneic model of uPAR overexpression by the rat breast cancer cell line Mat B
      III, we have examined the ability of the nonsteroidal antiestrogen, tamoxifen
      (TAM), and of a selective synthetic inhibitor of uPA, 4-iodo benzo[b]thiophene-2
      carboxamidine (B-428), to inhibit expression of uPA and uPAR as well as cell
      growth, invasion, and metastasis of wild-type Mat B-III cells and of cells
      overexpressing uPAR (Mat B-III-uPAR). Both TAM and B-428 inhibited uPAR gene
      transcription, mRNA expression, protein production and also decreased the
      proliferative and invasive capacity of Mat B-III and Mat B-III-uPAR. The effects
      of TAM and B-428 were more pronounced when these agents were tested in
      combination. Both control and experimental cells (1 x 10(6) cells) were
      inoculated orthotopically into the mammary fat pad of syngeneic female Fisher
      rats, and animals were infused i.p. with either TAM and B-428 alone or in
      combination for 2 weeks. Control animals receiving vehicle alone developed large
      tumors and macroscopic metastases to lungs, liver, and lymph nodes. In contrast
      to this, experimental animals receiving TAM and B-428 showed a significant
      decrease in primary tumor volume and metastases. Combination therapy had
      especially marked effects in blocking progression of the primary tumor in
      experimental animals inoculated with highly aggressive Mat B-III-uPAR cells.
      These results underscore the utility of anti-proteolytic agents (B-428) in
      addition to standard hormone therapy (TAM) in advanced breast cancer patients
      where the uPA/uPAR system plays a key role in tumor progression.

PMID- 9270033
TI  - Inhibition of prostate cancer neovascularization and growth by urokinase
      plasminogen activator receptor blockade.
AB  - Binding of the serine protease urokinase (u-PA) to its receptor on tumor cell
      surfaces facilitates proteolysis and tumor invasion. We undertook this study to
      determine whether the role of u-PA in prostate cancer induced angiogenesis and
      secondary tumor growth by developing a homologous, immunocompetent in vivo model
      in which the tumors cells secrete an inhibitor of the murine u-PA receptor. A
      mutant recombinant murine u-PA that retains receptor binding but not proteolytic
      activity was made by PCR mutagenesis. Mutant u-PA and a reporter gene pRK
      luciferase were transfected and stably expressed in the highly metastatic rat
      Dunning MAT-LyLu prostate cancer cell line. Several clones expressing mutant u-PA
      and luciferase were identified by Western blotting, plasminogen zymography, and
      reverse transcription-PCR. One of these clones, 5C4, was injected s.c. into
      Copenhagen rats. Compared to animals injected with clones expressing pRK
      luciferase alone, tumors in animals injected with 5C4 cells were significantly
      smaller. Moreover, there were fewer lung micrometastases in the 5C4 animals.
      Primary tumor angiogenesis was measured by microvessel quantification of tissue
      stained with antibodies against von Willebrand factor. Mean microvessel density
      in 5C4 tumors was 4.3-fold lower than that in animals with tumors derived from
      the control tumor cell line (P < 0.0001). Significant inhibition of tumor growth
      was also observed for two additional MAT-LyLu cell lines expressing mutant u-PA.
      These findings suggest that cell surface u-PA contributes to prostate cancer
      growth by enhancing angiogenesis.

PMID- 9270034
TI  - Resistance to radiation-induced apoptosis in Burkitt's lymphoma cells is
      associated with defective ceramide signaling.
AB  - Increased sensitivity to ionizing radiation has been shown to be due to defects
      in double-strand break repair and mutations in the proteins that detect DNA
      damage. However, it is now recognized that the cellular radiation response is
      complex and that radioresistance/radiosensitivity may also be regulated at
      different levels in the radiation signal transduction pathway. Here, we describe
      a direct relationship between resistance to radiation-induced apoptosis and
      defective ceramide signaling. Radiation sensitivity in human tumor cells
      correlated with the immediate accumulation of the second messenger ceramide. In
      the BL30A Burkitt's lymphoma line, ceramide increased 4-fold by 10 min
      postirradiation (10 Gy), and in the moderately sensitive HL-60 leukemia cells,
      ceramide accumulated 2.5-fold above basal levels. In contrast, in all
      radioresistant tumor cells examined, including several Burkitt's lymphoma lines
      (BL30K, BL29, and BL36) and the MO59K glioma cell line, ceramide did not
      accumulate postirradiation. The ability to abrogate ceramide production by
      pretreatment with the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate,
      conferred resistance to radiation-induced apoptosis in the sensitive BL30A cells.
      An isogenic subline of BL30A, BL30K, was resistant to both C8-ceramide (20
      microM) and ionizing radiation-induced apoptosis. Bypassing the block in
      radiation-induced ceramide production by the addition of exogenous ceramide was
      not sufficient to induce apoptosis; this suggests the existence of a second
      ceramide-associated signaling defect in these radioresistant cells that confers
      resistance to ceramide-induced apoptosis. Thus, these results provide compelling
      evidence that ceramide is an essential mediator of radiation-induced apoptosis
      and that defective ceramide signaling confers an apoptosis-resistant phenotype in
      tumor cells.

PMID- 9270035
TI  - Synergy between transforming growth factor alpha and hepatitis B virus surface
      antigen in hepatocellular proliferation and carcinogenesis.
AB  - Chronic infection with hepatitis B virus (HBV) can cause liver cancer in humans.
      Transgenic mice expressing the major envelope protein of HBV, HBV surface antigen
      (HBsAg), represent an experimental model for some of the histopathological
      effects of infection in humans, including prolonged hepatocellular injury,
      necrosis, hyperplasia, and an elevated incidence of liver tumors. The
      regenerative hyperplastic response to the chronic liver damage is thought to be a
      critical factor in the increased risk of cancer. However, little is known about
      the cellular factors that mediate regenerative proliferation. One candidate is
      the hepatocyte mitogen transforming growth factor alpha (TGF-alpha); in HBV
      infected patients with liver cancer, TGF-alpha and HBsAg accumulate in the same
      hepatocytes. Transgenic mice overexpressing TGF-alpha demonstrate enhanced
      hepatocyte proliferation rates and develop hepatocellular carcinomas. In this
      study, we have analyzed the effect of TGF-alpha and HBsAg coexpression in the
      liver using a bitransgenic mouse model. We show that hepatocytes harboring both
      the TGF-alpha and HBsAg transgenes exhibited an increase in growth relative to
      hepatocytes with either transgene alone. Furthermore, bitransgenic males but not
      females had a dramatically accelerated appearance of hepatocellular carcinomas,
      compared to single transgenic TGF-alpha or HBsAg littermates. These results
      demonstrate synergistic activity between HBsAg and TGF-alpha in the liver,
      probably by first stimulating quiescent hepatocytes to enter G1 and by
      subsequently promoting their transit through the cell cycle, respectively.
      Moreover, our data support the contention that TGF-alpha participates in HBV
      induced hepatocarcinogenesis in infected patients.

PMID- 9270036
TI  - Tumor cells with organ-specific metastatic ability show distinctive trafficking
      in vivo: analyses by positron emission tomography and bioimaging.
AB  - To elucidate the behavior of various metastatic tumor cells with different
      characteristics in the blood flow, we have developed a system to investigate real
      time trafficking using positron emission tomography. In this study, positron
      labeled cells, i.e., lung-metastatic B16BL6 melanoma and two sublines of liver
      metastatic RAW117 large cell lymphoma, were injected i.v., and the trafficking of
      these cells was noninvasively determined. All sublines tested accumulated in the
      lungs immediately after injection, presumably because the lungs were the first
      organ passed through after i.v. injection. The elimination of RAW117 cells from
      the lungs, however, was fast compared with that of B16BL6 cells. The latter
      showed a release rate from the lungs of less than 1%/min, whereas that of RAW117
      cells was greater than 2%/min. Reflecting the elimination from lungs, RAW117
      cells accumulated in the liver in a time-dependent manner. Biodistribution of
      metastatic cells was also analyzed by whole-body autoradiography after injection
      of 5-[125I]iodo-2'-deoxyuridine-labeled cells, using a bioimaging analyzer
      system. The method is invasive; however, it enables a precise determination of
      the biodistribution of metastatic cells. Bioimaging analyzer system analysis also
      showed the organ-specific accumulation of these metastatic cells. Furthermore,
      colonized distribution of B16BL6 cells in the lungs and that of RAW117 cells in
      the liver were observed. The present data suggest that the trafficking of
      metastatic tumor cells greatly influences the organ specificity of cancer
      metastasis.

PMID- 9270037
TI  - Molecular mechanisms for inflammation-promoted pathogenesis of cancer--The
      Sixteenth International Symposium of the Sapporo Cancer Seminar.

PMID- 9270038
TI  - Survival of rat and porcine Sertoli cell transplants in the rat striatum without
      cyclosporine-A immunosuppression.
AB  - The use of cyclosporine-A (CsA) immunosuppression for neural transplantation has
      become the treatment of choice for ameliorating host-graft rejection responses in
      human and animal transplant studies. However, the cytotoxic effects of CsA have
      warranted a search for alternative methods of protecting neural transplants.
      Sertoli cells produce an immunosuppressant factor, Fas ligand (Fas-L), that may
      provide the testis with its immunoprivileged status. Therefore, it has recently
      been suggested that these cells may be useful in producing localized
      immunosuppression for transplants. If Sertoli cells do produce localized
      immunosuppression, then it should be possible to successfully transplant Sertoli
      cells without additional immunosuppression following transplant surgery. The
      present study was undertaken to determine whether rat or porcine Sertoli cells
      transplanted into rat brain would survive for an extended period of time without
      CsA immunosuppression. Isolated rat or porcine Sertoli cells prelabeled with DiI
      were transplanted into normal rat brain. We report that both rat Sertoli cell
      allografts and porcine Sertoli cell xenografts survived for at least 2 months
      posttransplantation into the rat brain without CsA immunosuppression, indicating
      that these grafts were capable of producing sufficient localized
      immunosuppression to survive at the site of transplant without additional
      systemic immunosuppression.

PMID- 9270039
TI  - Intracerebroventricular transplantation of embryonic neuronal tissue from
      inflammatory resistant into inflammatory susceptible rats suppresses specific
      components of inflammation.
AB  - To more directly define the role of central nervous system factors in
      susceptibility to peripheral inflammatory disease, we examined the effect of
      intracerebroventricular transplantation of neuronal tissue from inflammatory
      resistant into inflammatory susceptible rats on subcutaneous carrageenan-induced
      inflammation (a measure of innate immunity), and on the relative percentage of
      naive and memory T helper cells in peripheral blood (a measure of the anamnestic
      immune response). Female inflammatory disease susceptible Lewis (LEW/N) rats
      transplanted with hypothalamic tissue from inflammatory resistant Fischer
      (F344/N) rats exhibited > 85% decrease in carrageenan inflammation compared to
      naive LEW/N rats, LEW/N rats transplanted with F344/N spinal cord, or sham
      operated animals. LEW/N rats transplanted with LEW/N hypothalamic tissue
      exhibited > 50% decrease in carrageenan inflammation. In contrast,
      intracerebroventricular transplantation of neuronal tissue did not affect the
      characteristically twofold higher percentage of naive versus memory T helper
      cells in LEW/N rats, suggesting that the central nervous system (CNS) and
      hypothalamus play a greater role in the innate inflammatory response than in the
      acquired immune processes. Grafted tissue survived well and did not show
      extensive gliosis or inflammation. Compared to naive LEW/N rats, LEW/N rats
      transplanted with F344/N or LEW/N hypothalamic tissue expressed significantly
      greater hypothalamic corticotropin releasing hormone mRNA. LEW/N rats
      transplanted with F344/N hypothalamic tissue also showed significant increases in
      plasma corticosterone responses to lipopolysaccharide. These data indicate that
      intracerebroventricular transplantation of fetal hypothalamic tissue from
      inflammatory resistant into inflammatory susceptible rats suppresses peripheral
      inflammation partially through hypothalamic factors. These findings have
      implications for understanding the contribution of specific neuronal tissue in
      regulation of components of the immune/inflammatory response and in
      susceptibility to inflammatory disease. Furthermore, this model could be used in
      the development of potential new treatments for inflammatory/autoimmune diseases
      aimed specifically at sites within the CNS.

PMID- 9270040
TI  - Retino-geniculate axons regenerating in adult hamsters are able to form
      morphologically distinct terminals.
AB  - Adult mammalian retinal ganglion cells (RGCs) can regenerate through peripheral
      nerve (PN) grafts and innervate central nervous system (CNS) targets. Previous
      studies have demonstrated a basic level of differentiation of such projections.
      To further assess the specificity and functionality of regenerated CNS
      connections we have developed a new model in which RGCs are directed through a PN
      graft into the dorsolateral geniculate body (LGBd) while preserving the visual
      cortex and radiations. We also describe by light microscopy that regenerating RGC
      axons which enter the LGBd differentiate and form subtypes of RGC terminals
      reminiscent of those seen in the normal LGBd. Thus the adult CNS contains cues
      that permit phenotypic differentiation of terminal types during regeneration.

PMID- 9270041
TI  - Characterization of target cells for aberrant mossy fiber collaterals in the
      dentate gyrus of epileptic rat.
AB  - Previous studies have demonstrated formation of recurrent excitatory circuits
      between sprouted mossy fibers and granule cell dendrites in the inner molecular
      layer of the dentate gyrus (9, 28, 30). In addition, there is evidence that
      inhibitory nonprincipal cells also receive an input from sprouted mossy fibers
      (39). This study was undertaken to further characterize possible target cells for
      sprouted mossy fibers, using immunofluorescent staining for different calcium
      binding proteins in combination with Timm histochemical staining for mossy
      fibers. Rats were injected intraperitoneally with kainic acid in order to induce
      epileptic convulsions and mossy fiber sprouting. After 2 months survival,
      hippocampal sections were immunostained for parvalbumin, calbindin D28k, or
      calretinin followed by Timm-staining. Under a fluorescent microscope, zinc
      positive mossy fibers in epileptic rats were found to surround parvalbumin
      containing neurons in the granule cell layer and to follow their dendrites, which
      extended toward the molecular layer. In addition, dendrites of calbindin D28k
      containing cells were covered by multiple mossy fiber terminals in the inner
      molecular layer. However, the calretinin-containing cell bodies in the granule
      cell layer did not receive any contacts from the sprouted fibers. Electron
      microscopic analysis revealed that typical Timm-positive mossy fiber terminals
      established several asymmetrical synapses with the soma and dendrites of
      nonpyramidal cells within the granule cell layer. These results provide direct
      evidence that, in addition to recurrent excitatory connections, inhibitory
      circuitries, especially those responsible for the perisomatic feedback
      inhibition, are formed as a result of mossy fiber sprouting in experimental
      epilepsy.

PMID- 9270043
TI  - Seizures and proto-oncogene expression of fos in the brain of adult genetically
      epilepsy-prone rats.
AB  - The mechanisms and brain circuitry that render genetically epilepsy-prone rats
      (GEPRs) susceptible to acoustically induced seizures are not completely known.
      The present study explores the neuroanatomy of acoustically induced seizures by
      immunohistochemical analysis of the proto-oncoprotein fos after intense acoustic
      stimulation (AS) with and without seizures. Acoustic stimulation induced tonic
      convulsions in GEPR-9s, but not in control rats. Locations of brain nuclei
      showing fos-like immunoreactive (FLI) neurons following AS with and without
      seizures were mapped. Semiquantitative methods were used to compare FLI neuron
      numerical densities in AS control rats and GEPRs. Many brain areas exhibited
      profound FLI in AS control rats and GEPRs. Unexpectedly, the cochlear nuclei and
      the central nucleus of the inferior colliculi (ICc), both of which are requisite
      for AGS initiation, exhibited a diminished fos expression in animals having
      seizures compared to AS controls. In contrast, GEPRs displayed a significant
      increase in FLI neurons within the dorsal cortex of the IC (ICd) compared to AS
      controls. This finding may suggest a seizure-related amplification of the
      auditory signal between the ICc and the ICd. Other nuclei, known to be involved
      in auditory transmission (i.e., superior olivary complex; trapezoid nucleus;
      dorsal nucleus of the lateral lemniscus, DNLL), did not show differential FLI
      densities between seizure and AS control animals. In contrast, seizure-induced
      FLI was observed in many nonauditory brain nuclei. Of particular interest was the
      identification of an intensely labeled nucleus in the GEPR. This nucleus resides
      in the most posterior and dorsal-lateral part of the pedunculopontine tegmental
      nucleus-pars compacta (PPTn-pc) immediately adjacent to the DNLL and extends
      posteriorly into the superior lateral subnucleus of the lateral parabrachial area
      (SLPBn). Therefore, we have tentatively termed this nucleus the PPSLPBn. The
      PPSLPBn lies in a region previously described as a mesencephalic locomotor region
      and a suspected functional involvement of this nucleus in display of seizure
      activity is under investigation. Other brain stem nuclei showing differential fos
      expression between GEPRs and AS control rats are also described.

PMID- 9270042
TI  - Glutathione and glutathione S-transferase in the rainbow trout olfactory mucosa
      during retrograde degeneration and regeneration of the olfactory nerve.
AB  - In the peripheral olfactory organ, continual olfactory receptor neuron (ORN)
      turnover exposes neighboring cells to potentially damaging cellular debris such
      as free radicals. These, in turn, may be inactivated by binding directly onto
      glutathione (GSH) or by enzymatic conjugation with glutathione S-transferase
      (GST). In this study, we have investigated GSH and GST during retrograde
      degeneration and regeneration of the olfactory nerve in rainbow trout. In these
      fish, prolonged ORN physiological activity and structural integrity following
      transection of the olfactory nerve may be mediated by GSH and GST. In the
      olfactory mucosa, early changes following nerve lesion and prior to ORN
      degeneration included a shift of intense GSH labeling from the dendrites and
      perikarya of a subpopulation of ORN, and from melanophores, to olfactory nerve
      fascicles. GSH levels were unchanged, but GST activity decreased by 33% and GST
      immunoreactivity (GST-IR) in nerve fascicles diminished slightly. When the
      process of massive degeneration terminated and ORN were largely absent, GSH
      levels and GST activity decreased further, GSH labeling was confined to
      melanophores, and GST-IR was absent. As ORN repopulated the olfactory mucosa, GST
      IR was widespread. The combination of increased GST activity (92% of preoperative
      values) and low GSH levels suggests GSH utilization for GST conjugation
      reactions. These changes imply that GSH provides protection from cellular debris
      associated with ORN degeneration. Recovery of GST activity and widespread GST-IR
      during regeneration indicates modulation of neuroprotective, developmental,
      and/or physiological processes by GST.

PMID- 9270044
TI  - Amyotrophic lateral sclerosis immunoglobulins increase intracellular calcium in a
      motoneuron cell line.
AB  - A hybrid motoneuron cell line (VSC4.1) was used as a model system to study the
      relationship between alterations in intracellular calcium and subsequent cell
      death induced by immunoglobulin fractions purified from sera of patients with
      ALS. Using fluo-3 fluorescence imaging, immunoglobulins from 8 of 10 patients
      with ALS were found to induce transient increases in intracellular calcium
      ([Ca2+]i) in differentiated VSC4.1 cells. These transient [Ca2+]i increases
      required extracellular calcium entry through voltage-gated calcium channels
      sensitive to synthetic FTX and to high concentrations (>1 microM) of omega
      agatoxin IVa. The incidence of transient [Ca2+]i increases induced by ALS
      immunoglobulins correlated with the extent of cytotoxicity induced by the same
      ALS immunoglobulins in parallel cultures of VSC4.1 cells. Furthermore,
      manipulations which blocked transient [Ca2+]i increases (addition of synthetic
      FTX or omega-agatoxin IVa) also inhibited the cytotoxic effects of ALS
      immunoglobulins. No transient calcium increases were observed in VSC4.1 cells
      following addition of immunoglobulins from 7 neurologic disease control patients.
      However, transient [Ca2+]i increases were observed following addition of
      immunoglobulins from 4 of 5 patients with myasthenia gravis (MG). The [Ca2+]i
      changes induced by MG immunoglobulins were not blocked by s-FTX, suggesting that
      they result from a different mechanism than those induced by ALS immunoglobulins.
      These results suggest that immunoglobulins from patients with ALS can induce
      transient increases in intracellular calcium in a motoneuron cell line, which may
      represent early events in the cascade of processes leading to injury and death of
      susceptible cells.

PMID- 9270045
TI  - Plasticity of galaninergic fibers following neurotoxic damage within the rat
      basal forebrain: initial observations.
AB  - Galanin immunoreactive fibers hypertrophy and hyperinnervate remaining
      cholinergic basal forebrain neurons within the septum-diagonal band complex in
      Alzheimer's disease. The present investigation determined whether a similar
      hyperinnervation of galanin immunoreactive fibers occurs following
      intraparenchymal injections of ibotenic acid within the cholinergic medial septum
      or diagonal band nucleus in young adult rats. Sections through the medial septum
      and the diagonal band were either concurrently immunostained for galanin and the
      low-affinity p75 neurotrophin receptor (an excellent marker of cholinergic basal
      forebrain neurons) or single stained for choline acetyltransferase. Following
      chemical lesion, an increase in the density of galanin immunoreactivity was seen
      within the medial septum on the lesion, as opposed to the contralateral control
      side. In contrast, within diagonal band-lesioned animals, the increase in galanin
      immunoreactivity was low to moderate. In either lesion paradigm we did not
      observe hyperinnervation of remaining cholinergic basal forebrain neurons. In
      fact, there was no correlation between the galanin hypertrophy and the amount of
      cholinergic cell loss. We hypothesize that galanin hyperinnervation within the
      cholinergic basal forebrain may provide a protective effect by down-regulating
      acetylcholine release following brain insult.

PMID- 9270046
TI  - Blood-brain barrier permeability to ebiratide and TNF in acute spinal cord
      injury.
AB  - Spinal cord injury (SCI) in mammals has a poor outcome because of a lack of
      regeneration. Alteration of the local environment after injury may induce
      regeneration. However, the passage of blood-borne or exogenous neurotrophic
      substances through the blood-brain barrier (BBB) is not well characterized in
      either normal or injured states. We investigated the permeability of the BBB in
      normal and injured states to two markers of permeability (albumin and sucrose),
      to a peptide (ebiratide), and to a cytokine [tumor necrosis factor-alpha(TNF)].
      We found that in normal mice the cervical and lumbar areas of the spinal cord
      were more permeable than the thoracic area and the brain to all four substances.
      The penetration of the alpha-MSH/ACTH analogue ebiratide and of TNF, substances
      that have saturable transport systems across the BBB and may be involved in
      regenerative processes in the CNS, followed a regional pattern of differential
      permeability comparable to that of albumin and sucrose. Complete transection at
      the lumbar level induced a temporal change in the permeability of the BBB. The
      increased permeability, as measured by the radioactively labeled tracers albumin
      and sucrose, was most apparent in the lumbar region proximal to the transection.
      After SCI, the permeability to ebiratide remained unchanged, suggesting that
      disruption of the BBB did not affect the transport system for ebiratide. By
      contrast, the increase of permeability to TNF exceeded that detected by the
      markers albumin and sucrose. This enhanced permeability was inhibited by excess
      unlabeled TNF in the blood, showing saturability. This suggests that the
      transport system for TNF may be activated in SCI.

PMID- 9270047
TI  - Effects of axotomy and testosterone on androgen receptor mRNA expression in
      hamster facial motoneurons.
AB  - We have previously demonstrated that testosterone propionate (TP) treatment
      accelerates the rate of regeneration following facial nerve crush axotomy in
      adult male hamsters. These effects are mediated by androgen receptor (AR)
      activation and are blocked by pretreatment with the AR antagonist, flutamide. In
      addition to its beneficial effects on regeneration, TP regulates AR mRNA levels
      in facial motor neurons (FMN). Gonadectomized (gdx) male hamsters have been shown
      to have approximately 50% of the AR mRNA levels found in gonadally intact males.
      Administration of TP to gdx males results in an upregulation in AR mRNA levels
      after 1 day of treatment. Recent reports in the literature suggest that axotomy
      also may regulate the expression of AR in motor neurons. In this study, we
      examined the effects of axotomy and exogenous steroid treatment on the regulation
      of AR mRNA in hamster FMN. Five days after castration, adult male hamsters were
      subjected to a right facial nerve axotomy. Half the animals received one 10-mm
      Silastic capsule filled with 100% crystalline TP, and the remainder were sham
      implanted. Postoperative survival times were 6 h or 1, 2, 4, 7, or 14 days. In
      situ hybridization in conjunction with an AR riboprobe and computerized image
      analysis were used to quantify AR mRNA levels. The contralateral FMN served as
      internal controls for these experiments, and FMN of gonadally intact males served
      as additional nonaxotomized controls. As predicted, AR mRNA levels were
      upregulated in contralateral control FMN after TP treatment. However, this TP
      induced upregulation of AR mRNA levels did not occur in the axotomized FMN. These
      results indicate that axonal injury can disrupt the normal regulatory pattern of
      AR mRNA expression by exogenous steroids in motoneurons. We conclude that the
      potentiation of regenerative events by TP does not require augmented synthesis of
      AR, but, instead, enhanced stabilization of existing receptors.

PMID- 9270048
TI  - Altered immunoreactivity for glial fibrillary acidic protein in astrocytes within
      1 h after cervical spinal cord injury.
AB  - One hour after a C2 spinal cord hemisection, there are changes in astrocyte
      morphology and increased glial fibrillary acidic protein immunoreactivity (GFAP
      IR) near the site of the lesion. Astrocytes adjacent to the lesion display thick,
      richly branched processes within 1/2 segment rostral and caudal to the level of
      hemisection. Astrocytes are also enlarged and immunoreactive in gray matter
      regions of the spinal cord as far caudal as C4 and rostrally to C1. Sham-operated
      controls, undergoing a laminectomy and durotomy at C2, but not spinal cord
      hemisection, also exhibit a strong astroglial reaction within 1 h from C1 to C4.
      However, controls undergoing only a C2 laminectomy do not demonstrate alterations
      in GFAP IR compared to non-operated controls. The results of this investigation
      suggest that spinal cord astrocytes are extremely sensitive to both major as well
      as minor alterations of their microenvironment. Rapid changes in astroglial
      morphology, as detected by altered GFAP IR, may play a role in changes in
      neuronal function following spinal cord injury.

PMID- 9270049
TI  - Beta-amyloid peptides initiate the complement cascade without producing a
      comparable effect on the terminal pathway in vitro.
AB  - Activation of the classical complement cascade by beta-amyloid peptides has been
      hypothesized to underlie the neurodegeneration observed in Alzheimer's diseased
      brains. In this study, various lots of synthetic beta-amyloid peptides, A beta(1
      40), A beta(1-42), and A beta(25-35), were tested for their ability to activate
      both early complement cascade events and formation of the membrane attack complex
      through terminal pathway activation. Unlike recent reports which did not assess
      activation of complement terminal pathway, we found that concentrations of beta
      amyloid which activated early cascade events, to an extent comparable to
      aggregated IgG, failed to elicit formation of comparable levels of membrane
      attack complex.

PMID- 9270050
TI  - Gel matrix vehicles for growth factor application in nerve gap injuries repaired
      with tubes: a comparison of biomatrix, collagen, and methylcellulose.
AB  - The repair of nerve gap injuries with tubular nerve guides has been used
      extensively as an in vivo test model in identifying substances which may enhance
      nerve regeneration. The model has also been used clinical nerve repair. The
      objective of this study was to compare three different gel matrix-forming
      materials as potential vehicles for growth factors in this system. The vehicles
      included a laminin containing extracellular matrix preparation (Biomatrix),
      collagen, and a 2% methylcellulose gel. The growth factor test substance
      consisted of a combination of platelet-derived growth factor BB (PDGF-BB) and
      insulin-like growth factor I (IGF-I). An 8-mm gap in rat sciatic nerve was
      repaired with a silicone tube containing each of the vehicles alone or with a
      combination of each vehicle plus PDGF-BB and IGF-I. At 4 weeks after injury, the
      application of the growth factor combination significantly stimulated axonal
      regeneration when applied in methylcellulose or collagen, but not in Biomatrix. A
      similar trend was present between the vehicle control groups. By 8 weeks after
      injury, nerves repaired with methylcellulose as a vehicle had significantly
      greater conduction velocity than either collagen or Biomatrix. It was concluded
      that a 2% methylcellulose gel was the best of the three matrices tested, both in
      its effects on nerve regeneration and flexibility of formulation.

PMID- 9270051
TI  - Anoxia-induced neuronal injury: role of Na+ entry and Na+-dependent transport.
AB  - An important cause of anoxia-induced nerve injury involves the disruption of the
      ionic balance that exists across the neuronal membrane. This loss of ionic
      homeostasis results in an increase in intracellular calcium, sodium, and hydrogen
      and is correlated with cell injury and death. Using time-lapse confocal
      microscopy, we have previously reported that nerve cell injury is mediated
      largely by sodium and that removing extracellular sodium prevents the anoxia
      induced morphological changes. In this study, we hypothesized that sodium enters
      neurons via specific mechanisms and that the pharmacologic blockade of sodium
      entry would prevent nerve damage. In cultured neocortical neurons we demonstrate
      that replacing extracellular sodium with NMDG+ prevents anoxia-induced
      morphological changes. With sodium in the extracellular fluid, various routes of
      sodium entry were examined, including voltage-sensitive sodium channels,
      glutamate receptor channels, and sodium-dependent chloride-bicarbonate exchange.
      Blockade of these routes had no effect. Amiloride, however, prevented the
      morphological changes induced by anoxia lasting 10, 15, or 20 min. At doses of 10
      microM-1 mM, amiloride protected neurons in a dose-dependent fashion. We argue
      that amiloride acts on a Na+-dependent exchanger (e.g., Na+-Ca2+) and present a
      model to explain these findings in the context of the neuronal response to
      anoxia.

PMID- 9270052
TI  - Parvalbumin- and calbindin D-28k-immunoreactive innervation of orofacial tissues
      in the rat.
AB  - Parvalbumin- and calbindin D-28k-immunoreactive (-ir) innervation was examined in
      orofacial tissues of the rat. Labial and facial skins were devoid of the calcium
      binding protein (CaBP)-ir nerve endings, while the infraorbital and mental nerves
      contained numerous parvalbumin-ir axons. Labial and gingival mucosae were also
      devoid of the CaBP-ir nerve endings. The buccal mucosa and incisive papilla
      contained both encapsulated and unencapsulated endings, while the hard palate
      mucosa excluding the incisive papilla contained only unencapsulated endings.
      Encapsulated endings were found just beneath the epithelium or attached to the
      cartilaginous core of the incisive papilla. Unencapsulated endings in the lamina
      propria were subdivided into two types: simple (unramified) and complex
      (ramified). Neurites of simple endings were straight, curved, or coiled, while
      those of complex endings exhibited a bush-like appearance due to the
      ramification. In addition, palatal rugae contained intraepithelial endings. The
      unencapsulated complex endings in palatal rugae coexpressed parvalbumin- and
      calbindin D-28k-irs, whereas other endings were immunoreactive for parvalbumin
      alone. The pterygopalatine ganglion contained calbindin D-28k-ir pericellular
      fibers but not the ir cell bodies. A subpopulation of trigeminal ganglion neurons
      coexpressed both CaBPs. CaBP-ir encapsulated and unencapsulated endings in the
      oral mucosa probably include low-threshold mechanoreceptors, while parvalbumin-ir
      intraepithelial endings in the palatal mucosa may be involved in nociception.

PMID- 9270053
TI  - Ultrastructural and biochemical studies on the neuroprotective effects of
      excitatory amino acid antagonists in the ischemic rat retina.
AB  - The effects of glutamate receptor agonists were evaluated, by utilizing the
      electron microscope, in a photothrombotic occlusion model of rat retinal vessels
      in order to study the ischemic damage and its antagonism in each morphologically
      identified population of retinal neurons. Rats were systemically injected with
      rose bengal fluorescein dye and one of their eyes was then exposed to bright
      light. This treatment caused neuronal damage and reduced the activities of the
      neuronal marker enzymes, choline acetyltransferase and glutamate decarboxylase,
      by approximately 75%. A single intravitreal injection of 2,3-dihydroxy-6-nitro-7
      sulfamoylbenzoquinoxaline (NBQX, 10-50 nmol), an antagonist of alpha-amino-3
      hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors, or of
      thiokynurenate (100-400 nmol), which also antagonizes N-methyl-D-aspartate (NMDA)
      receptors, performed immediately after the lesion, significantly reduced this
      loss. The electron microscope examination showed major damage in each type of
      retinal neuron, the pigment epithelium, and the microvessels. NBQX or
      thiokynurenic acid reduced, in a comparable manner, the effects of ischemia on
      the pigment epithelium, the photoreceptors, and the bipolar and the horizontal
      cells. NBQX was particularly efficient in reducing the damage to the amacrine
      cells located in the inner nuclear layer. The displaced amacrine and ganglion
      cells were not protected by NBQX but were almost completely spared in animals
      treated with thiokynurenate. These results show that antagonism of AMPA receptors
      is sufficient to reduce ischemic damage in a large number of retinal neurons, but
      that neuroprotection in the ganglion cell layer may be obtained only with agents
      which also antagonize NMDA receptors.

PMID- 9270054
TI  - Postischemic infusion of Cu/Zn superoxide dismutase or SOD:Tet451 reduces
      cerebral infarction following focal ischemia/reperfusion in rats.
AB  - Oxygen-free radicals play a major role in neuronal cell injury following cerebral
      ischemia/reperfusion. The free-radical scavenging enzyme, Cu/Zn superoxide
      dismutase (SOD-1), ameliorates various types of brain injury resulting from
      temporary CNS ischemia. We have compared the cerebroprotective properties of
      human SOD-1 (hSOD-1) with a novel recombinant SOD-1 hybrid protein, SOD:Tet451,
      composed of hSOD-1 linked to the neuronal binding fragment of tetanus toxin
      (TTxC). Following 2 h of temporary middle cerebral artery occlusion, rats infused
      with equivalent activities of either hSOD-1 or SOD:Tet451 for the initial 3 h of
      reperfusion showed reductions in cerebral infarct volume of 43 and 57%,
      respectively, compared to saline-treated controls (P < 0.01). Serum hSOD-1
      concentrations in rats receiving SOD:Tet451 were seven-fold higher than those in
      rats receiving the native enzyme. Animals treated with SOD:Tet451 also
      demonstrated an extended persistence of hSOD-1 in the bloodstream during drug
      washout as compared to animals given free enzyme. Immunohistochemical examination
      of brain sections from an SOD:Tet451-treated ischemic rat showed positive
      immunoreactivity in the ipsilateral cerebral cortex using either anti-TTxC or
      anti-human SOD-1 antibodies. Our results document that both hSOD-1 and SOD:Tet451
      significantly reduce brain infarct volume in a model of transient focal
      ischemia/reperfusion in rats. Additionally, our findings suggest that the
      cerebroprotective effects of SOD-1 may be enhanced by neuronal targeting as seen
      with the hybrid protein SOD:Tet451.

PMID- 9270055
TI  - Age-dependent differences in survival of striatal somatostatin-NPY-NADPH
      diaphorase-containing interneurons versus striatal projection neurons after
      intrastriatal injection of quinolinic acid in rats.
AB  - Some authors have reported greater sparing of neurons containing somatostatin
      (SS)-neuropeptide Y (NPY)-NADPH-diaphorase (NADPHd) than projection neurons after
      intrastriatal injection of quinolinic acid (QA), an excitotoxin acting at NMDA
      receptors. Such findings have been used to support the NMDA receptor excitotoxin
      hypothesis of Huntington's disease (HD) and to claim that intrastriatal QA
      produces an animal model of HD. Other studies have, however, reported that
      SS/NPY/NADPHd interneurons are highly vulnerable to QA. We examined the influence
      of animal age (young versus mature), QA concentration (225 mM versus 50 mM), and
      injection speed (3 min versus 15 min) on the relative SS/NPY/NADPHd neuron
      survival in eight groups of rats that varied along these parameters to determine
      the basis of such prior discrepancies. Two weeks after QA injection, we analyzed
      the relative survival of neurons labeled by NADPHd histochemistry, SS/NPY
      immunohistochemistry, or cresyl violet staining (which stains all striatal
      neurons, the majority of which are projection neurons) in the so-called lesion
      transition zone (i.e., the zone of 40-60% neuronal survival). We found that age,
      and to a lesser extent injection speed, had a significant effect on relative
      SS/NPY/NADPHd interneuron survival. The NADPHd- and SS/NPY-labeled neurons
      typically survived better than projection neurons in young rats and more poorly
      in mature rats. This trend was greatly accentuated with fast QA injection. Age
      related differences may be attributable to declines in projection neuron
      sensitivity to QA with age. Since rapid QA injections result in excitotoxin
      efflux, we interpret the effect of injection speed to suggest that brief exposure
      to a large dose of QA (with fast injection) may better accentuate the
      differential vulnerabilities of NADPHd/SS/NPY interneurons and projection neurons
      than does exposure to the same total amount of QA delivered more gradually (slow
      injection). These findings reconcile the discordant results found by previous
      authors and suggest that QA injected into rat striatum does reproduce the
      neurochemical traits of HD under some circumstances. These findings are
      consistent with a role of excitotoxicity in HD pathogenesis, and they also have
      implications for the basis of the more pernicious nature of striatal neuron loss
      in juvenile onset HD.

PMID- 9270056
TI  - The expression of creatine kinase isoenzymes in neocortex of patients with
      neurodegenerative disorders: Alzheimer's and Pick's disease.
AB  - Creatine kinase (CK) activity was found decreased in the brains of patients with
      Alzheimer's disease (AD) and Pick's disease (PD). However, the decrease of total
      CK activity in AD was more pronounced than in PD. Analysis of the activity of two
      CK isoforms, BCK and ubiquitous mitochondrial CK, demonstrated that the decrease
      of total CK activity in AD and PD was related to the decrease of BCK activity.
      The decline of CK activity both in AD and PD correlated well with the decline of
      the content of immunoreactive BCK in brain extracts. The BCK mRNA level in AD and
      PD was not significantly different from control patients and could not be the
      primary reason for decreases in CK content and activity. The decreased level of
      BCK in AD and PD brains might be caused by posttranscriptional events, which
      could affect the translation of BCK mRNA and/or lead to the inactivation and
      degradation of the enzyme. Because CK is sensitive to oxidative modification, it
      is possible that the changes observed in this study result from free radical
      damage.

PMID- 9270057
TI  - The absence of synergism between the effects of an aldose reductase inhibitor,
      epalrestat, and a vasodilator, cilostazol, on the nerve conduction slowing and
      the myelinated fiber atrophy in streptozotocin-induced diabetic rats.
AB  - The preventive effects of combined or separate treatment for 10 weeks with an
      aldose reductase inhibitor, epalrestat (50 mg/kg/day), and a vasodilator,
      cilostazol (30 mg/kg/day), on nerve conduction deficits and morphometric
      alterations were examined in streptozotocin-induced diabetic rats. The average
      motor nerve conduction velocities (MNCV) in the tail nerve of the untreated
      diabetic (DM) group, the group treated with epalrestat (ES), the group treated
      with cilostazol (CZ), the group with both agents together (ES&CZ), and the normal
      control group were 34.7, 37.7, 39.3, 39.0 and 42.1 m/s, respectively. All
      treatments partially but significantly prevented a reduction in MNCV. The MNCV in
      the ES&CZ group was almost the same as in the CZ group. In a morphometric study
      of the sural nerve, the DM group showed a reduction in the average diameter of
      myelinated fiber and in occupancy (percentage of the fascicular area occupied by
      myelinated fibers), and a shift in the diameter-frequency histogram to smaller
      diameters. Only the CZ group showed evidence of a partial but significant
      preventive effect on the decrease in occupancy. In the CS and ES&CZ groups, there
      was a significant tendency away from the shift of histograms to smaller
      diameters. The ES&CZ group did not show any fewer morphometric changes than the
      CZ group. Thus, there was no synergism between the effects of epalrestat and
      cilostazol on the development of experimental diabetic neuropathy. This finding
      may provide a useful clue to the mechanisms of action of ES and CZ in diabetic
      neuropathy.

PMID- 9270058
TI  - The effect of chronic haloperidol treatment on dendritic spines in the rat
      striatum.
AB  - Previous studies have shown that schizophrenics, in comparison to controls, have
      reduced cortical spine density and smaller striatal spines. The current study in
      the rat was conducted to determine whether such differences could result from
      chronic neuroleptic treatment and whether they are correlated with neuroleptic
      induced oral dyskinesias. Rats administered 1.5 mg/kg/day of haloperidol (HA) (n
      = 28) or water (n = 10) were tested for vacuous chewing movements (VCMs). After 6
      months, rats were divided into low and high VCM groups; all but seven high VCM
      rats were sacrificed. These rats (withdrawn group) were withdrawn from HA for 4
      weeks. Random electron micrographs of the striatum were analyzed for spine
      changes. Spine size was not significantly affected by HA (0.193 vs 0.174 microm2,
      HA and control, respectively) nor correlated with oral dyskinesias (0.191 vs
      0.196 microm2, low and high VCM groups, respectively). These results suggest that
      smaller spines in schizophrenic striatum may be correlated with the disease
      rather than caused by neuroleptic treatment. Spine density decreased in the HA
      treated group (32.7 +/- 9.5) in comparison to controls (53.7 +/- 7.3, P < 0.001)
      and remained low in the withdrawn group (35.0 +/- 4.2, P < 0.01). Spine density
      also decreased in both the low (37.3 +/- 9.9, P < 0.01) and the high (28.0 +/-
      7.0, P < 0.000) VCM groups in comparison to controls. However, there was no
      significant difference between high and low VCM groups, suggesting that decreased
      spine density is independent of oral dyskinesias. These results suggest that the
      decreased spine density observed in schizophrenic cortex may be a result of
      neuroleptic treatment.

PMID- 9270059
TI  - Nerve growth factor attenuates cholinergic deficits following traumatic brain
      injury in rats.
AB  - Traumatic brain injury (TBI) results in chronic derangements in central
      cholinergic neurotransmission that may contribute to posttraumatic memory
      deficits. Intraventricular cannula (IVC) nerve growth factor (NGF) infusion can
      reduce axotomy-induced spatial memory deficits and morphologic changes observed
      in medial septal cholinergic neurons immunostained for choline acetyltransferase
      (ChAT). We examined the efficacy of NGF to (1) ameliorate reduced posttraumatic
      spatial memory performance, (2) release of hippocampal acetylcholine (ACh), and
      (3) ChAT immunoreactivity in the rat medial septum. Rats (n = 36) were trained
      prior to TBI on the functional tasks and retested on Days 1-5 (motor) and on Day
      7 (memory retention). Immediately following injury, an IVC and osmotic pump were
      implanted, and NGF or vehicle was infused for 7 days. While there were no
      differences in motor performance, the NGF-treated group had significantly better
      spatial memory retention (P < 0.05) than the vehicle-treated group. The IVC
      cannula was then removed on Day 7, and a microdialysis probe was placed into the
      dorsal hippocampus. After a 22-h equilibration period, samples were collected
      prior to and after administration of scopolamine (1 mg/kg), which evoked ACh
      release by blocking autoreceptors. The posttraumatic reduction in scopolamine
      evoked ACh release was completely reversed with NGF. Injury produced a bilateral
      reduction in the number and cross-sectional area of ChAT immunopositive medial
      septal neurons that was reversed by NGF treatment. These data suggest that
      cognitive but not motor deficits following TBI are, in part, mediated by chronic
      deficits in cholinergic systems that can be modulated by neurotrophic factors
      such as NGF.

PMID- 9270060
TI  - Increased axon number in the anterior commissure of mice lacking a corpus
      callosum.
AB  - Relatively few behavioral deficits are apparent in subjects with hereditary
      absence of the corpus callosum (CC). The anterior commissure (AC) has been
      suggested to provide an extracallosal route for the transfer of interhemispheric
      information in subjects with this congenital defect. Anterior commissure size,
      axon number, axon diameter, and neuronal distribution were compared between
      normal mice and those with complete CC absence. No difference in midsagittal AC
      area was found between normals and acallosals, nor were differences found in the
      numbers or diameters of myelinated axons. However, axon counts indicated an 17%
      increase or about 70,000 more unmyelinated axons in the AC of acallosal mice, and
      the mean diameter of unmyelinated axons was slightly less than in normal mice
      (0.24 vs 0.26 microm). This decrease in axon diameter enabled more axons to pass
      through the AC without increasing its midsagittal area. The topographical
      distribution of neurons sending axons through the AC, assessed with lipophilic
      dyes, was qualitatively similar for almost all the known regions of origin of the
      anterior commissure in normal and acallosal mice. There was a pronounced deficit
      of AC cells in the anterior piriform cortex of BALB/c mice, but this occurred
      whether or not the mouse suffered absent CC. Although the increase in AC axon
      number is far smaller than the number of CC axons that fail to reach the opposite
      hemisphere, the higher number of axons present in the AC of acallosal mice may
      contribute to the functional compensation for the loss of the CC.

PMID- 9270061
TI  - Novel differentially expressed genes induced by kainic acid in hippocampus:
      putative molecular effectors of plasticity and injury.
AB  - Systemic kainic acid administration in rats induces acute limbic status
      epilepticus and subsequent neuronal degeneration and development of chronic
      hyperexcitability with similarities to human temporal lobe epilepsy. The
      mechanisms mediating the responses to kainic acid likely involve transcriptional
      changes in genes of importance for cellular injury, protection, and plasticity.
      We have used an arbitrarily primed PCR technique to identify such changes in the
      rat dentate gyrus. Three previously uncharacterized transcripts were found to be
      upregulated in the dentate gyrus 4 h following systemic kainic acid. In situ
      hybridization using riboprobes transcribed from the cloned PCR fragments were
      used to confirm differential expression specifically in dentate granule neurons
      following seizure. Basal expression for all three transcripts is widespread
      throughout the rat brain, with the highest levels seen in the hippocampal
      pyramidal and granule cell layers. The novel sequences do not match any known
      full-length cDNAs and may belong to novel gene families. However, they all showed
      high homology to human partial cDNA sequences (ESTs) that are expressed in brain
      as well as several other tissues. Two additional transcripts identified in this
      study corroborate earlier findings on differential expression of heat-shock
      proteins after seizure. The novel transcripts found in this study may be involved
      in epileptogenesis and neuronal responses to damage following seizure.

PMID- 9270062
TI  - Nitric oxide reverses aspirin antagonism of t-PA thrombolysis in a rabbit model
      of thromboembolic stroke.
AB  - Randomized trials of thrombolytic therapy in stroke have reported an improvement
      in neurologic outcome; however, the addition of aspirin has resulted in a
      significant increase in mortality and antagonism of clot lysis in clinical and
      animal studies, respectively. This finding is in contradistinction to the known
      synergy in mortality reduction for aspirin and thrombolytics in myocardial
      infarction. It is hypothesized that aspirin antagonism of clot lysis is related
      to inhibition of nitric oxide (NO) and may be reversed by providing a source of
      NO. Twenty rabbits were treated with aspirin (20 mg/kg, i.v.) prior to internal
      carotid clot embolization. One-half hour following embolization, rabbits were
      randomized to receive vehicle (n = 5), the NO precursor L-arginine (300 mg/kg,
      i.v. bolus at 0.5 and 2.5 h postembolus; n = 5), or a nitric oxide donor
      (nitroprusside, 1 mg/kg/h, i.a., or nitroglycerin, 10 microg/kg/min, i.v., n = 5
      each agent). Tissue plasminogen activator (t-PA) (6.3 mg/kg) was administered
      from 1 to 3 h after embolization. Lysis of the tin-tagged clot was followed with
      serial X rays and gross examination. No rabbit in the control group experienced
      complete clot lysis. However, 2 of 5 rabbits in the L-arginine group and 6 of 10
      rabbits in the nitric oxide donor (nitroprusside and nitroglycerin) groups noted
      complete clot lysis (P < 0.05, Fisher exact test). Thus, administration of an NO
      donor (nitroglycerin or nitroprusside) and, to a lesser extent L-arginine,
      reversed aspirin's antagonism of t-PA thrombolysis. This study may help explain
      the discrepant results seen with aspirin and thrombolytics.

PMID- 9270063
TI  - Protective effects of peony root extract and its components on neuron damage in
      the hippocampus induced by the cobalt focus epilepsy model.
AB  - Protective effects of peony root extract and its components on neuron damage in
      the CA1 area of the hippocampus induced by the cobalt focus epilepsy model were
      examined. Neuron damage in the CA1 area of the hippocampus and frequent spike
      discharges induced by application of metallic cobalt to the cerebral cortex of
      rats were completely prevented when peony root extract was continuously
      administered orally at 1 g/kg/day for 30 days prior to cobalt application.
      Component crude gallotannin fraction showed marked but incomplete protective
      action. A combination of crude gallotannin fraction and paeoniflorin showed
      complete protective action in the same way as peony root extract against neuron
      damage although use of paeoniflorin alone had no effect. These findings together
      with our previous reports indicate that peony root extract and its component,
      gallotannin, have excellent protective effects on neuron damage in addition to
      anticonvulsant action by prior oral administration.

PMID- 9270064
TI  - Cyclosporin A attenuates the decrease in tyrosine hydroxylase immunoreactivity in
      nigrostriatal dopaminergic neurons and in striatal dopamine content in rats with
      intrastriatal injection of 6-hydroxydopamine.
AB  - To explore new therapeutic strategies for Parkinson's disease, we studied the
      possible protective effect of an immunosuppressant, cyclosporin A (CsA),
      treatment on changes in dopaminergic function in rats with intrastriatal
      injections of 6-hydroxydopamine (6-OHDA). Four weeks after injection of 6-OHDA,
      dopamine (DA) and dihydroxyphenylacetic acid in the striatum were depleted by 70
      80%, and repeated high-dose CsA (20 mg/kg) treatment for 1 week significantly
      protected against these depletions. Tyrosine hydroxylase immunoreactivity (TH-IR)
      of the cell bodies in the substantia nigra pars compacta (SNc) ipsilateral to the
      injection were lower than on the contralateral side at 4 weeks but not at 1 week
      after 6-OHDA injection. The number of TH-positive cell bodies in the SNc
      decreased to 64% but CsA treatment increased this to 87%. The staining of
      microglia in the SN with OX42 and Griffonia simplicifolia B4 isolectin was
      intense at 3 days and gradually decreased by 28 days after injection. At 3 and 7
      days after injection, the microglial staining in the SN was prominent and equal
      both in the 6-OHDA group and in ascorbic acid (SA)-injected controls. By 28 days
      postinjection, the staining had decreased to control levels in the SA group but
      was still above the control in the 6-OHDA group. CsA treatment did not affect
      this staining in either group. These results suggest that CsA protects against 6
      OHDA-induced injury of nigrostriatal DA neurons by a mechanism not involving
      microglia.

PMID- 9270065
TI  - Outcome following intrastriatal fetal mesencephalic grafts for Parkinson's
      patients is directly related to the volume of grafted tissue.
AB  - The effect of varying the volume of grafted fetal mesencephalic tissue was
      studied in patients with idiopathic Parkinson's disease in a single-blinded
      study. Evaluations were performed according to the Core Assessment Program for
      Intracerebral Transplantation and videotaped both prior to transplantation and in
      3-month intervals after transplantation. One group, low-volume grafts (six
      subjects; mean age, 57.2 years), received ventral mesencephalon grafts from one
      to two donors with an approximate volume up to 20 mm3, while the second group,
      high-volume grafts (seven subjects; mean age, 59.5 years), received ventral
      mesencephalon grafts from three or more donors with an approximate volume of 24
      mm3. Both groups of patients demonstrated significant improvement over
      presurgical baseline scores on all major parameters. The high-volume group had
      significantly greater improvements on all the UPDRS scores and also better
      performance on a variety of motor performance tasks over that seen among low
      volume patients. These results indicate that variations of fetal graft volume do
      have an impact on clinical outcome.

PMID- 9270066
TI  - Neurotoxic effects of kainic acid on substantia nigra neurons in rat brain
      slices.
AB  - Excitatory amino acids (EAAs) have been implicated as mediators of cell death in
      neurodegenerative diseases involving catecholamine neurons. Few studies, however,
      have examined the toxic effects of EAAs on identified catecholamine neurons in
      vitro. We have investigated the neurotoxic effects of kainic acid in a rat brain
      substantia nigra (SN) slice preparation. Rats (60-80 g) were anesthetised with
      halothane and killed by cervical dislocation. SN slices, 300 microm thick, were
      incubated at 35 degrees C in a modified Krebs solution in the presence or absence
      of kainic acid and then fixed and processed for either immunohistochemistry (IHC)
      or electron microscopy (EM). In IHC experiments, SN neurons were labeled using
      antibody to tyrosine hydroxylase (TH) coupled to diaminobenzidine. In control
      slices, the antibody labeled not only the cell body but also the prolific
      dendritic arbor of SN neurons. Treatment with 50 microM kainic acid for 15 min or
      2 h resulted in loss of TH staining and apparent fragmentation of the dendrites.
      EM provided ultrastructural evidence for kainic acid-induced degeneration of the
      dendritic arbor of SN neurons. Typically, the dendritic membrane was broken, or
      diffuse and collapsed. Ultrastructural damage, including clumping and
      marginalization of chromatin and vacuolation of the cytoplasm, was also observed
      in cell bodies. Damage to the dendritic arbor may occur early in the neurotoxic
      events leading to cell death, preceding the loss of the cell body. Our
      observations are consistent with the postulated role of EAAs as mediators of
      catecholamine neuron death.

PMID- 9270067
TI  - Enhancement by an ampakine of memory encoding in humans.
AB  - Acentrally active drug that enhances AMPA receptor-mediated currents was tested
      for its effects on memory in humans. Evidence for a positive influence on
      encoding was obtained in four tests: (i) visual associations, (ii) recognition of
      odors, (iii) acquisition of a visuospatial maze, and (iv) location and identity
      of playing cards. The drug did not improve scores in a task requiring cued recall
      of verbal information. The selectivity of drug effects on memory was confirmed
      using tests of visual recognition, motor performance, and general intellectual
      functioning. These results suggest that positive modulators of AMPA receptors
      selectively improve at least some aspects of memory.

PMID- 9270068
TI  - Platelet and lymphocyte benzodiazepine binding in patients with Alzheimer's
      disease.
AB  - Peripheral blood cells, such as platelets or lymphocytes, have been studied in
      the investigation of systemic derangements and central nervous system biochemical
      changes occurring in several neuropsychiatric disorders. In the present work,
      assaying platelet and lymphocyte peripheral-type benzodiazepine binding in
      patients with Alzheimer's disease (AD) and healthy controls, we found a
      significantly reduced number of cell receptors in patients' platelets and
      lymphocytes. These results are discussed with reference to central nervous system
      biochemical abnormalities in AD. Moreover, the lymphocyte binding data may
      represent an impairment of the immune response in AD, since lymphocyte surface
      peripheral-type benzodiazepine receptors seem to be related to immune function.

PMID- 9270069
TI  - Presenilin-1 polymorphism in Alzheimer's disease and vascular dementia.
AB  - Recent reports suggest an association between an intronic polymorphism at the 3'
      position of exon 8 of the presenilin-1 (PS-1) gene and late-onset Alzheimer's
      disease (AD), but little is known about its role in the pathogenesis of AD. By
      genotyping 193 Japanese patients with vascular dementia or AD, and 186 elderly
      control subjects, we have shown no association between vascular dementia and this
      PS-1 polymorphism, though PS-1 genotype 1/1 and allele 1 frequencies were both
      significantly higher among patients with AD than among controls. These results
      argue for a specific role of PS-1 allele 1 in the pathogenesis of AD, rather than
      suggesting a broader role for this allele as, for example, in vascular dementia.

PMID- 9270070
TI  - Formation of DNA adducts and oxidative base damage by copper mediated oxidation
      of dopamine and 6-hydroxydopamine.
AB  - We have investigated the formation of DNA adducts and oxidative base damage
      produced by copper sulfate activation of dopamine and 6-hydroxydopamine. In the
      presence of 10 microM copper sulfate both 100 microM dopamine and 100 microM 6
      hydroxydopamine formed three similar DNA adducts with relative adduct levels of
      8.36 +/- 2.23 x 10(-8) and 7.98 +/- 2.53 x 10(-8), respectively. The levels of 8
      hydroxy-2'-deoxyguanosine produced by these incubations were 5.2 +/- 0.03, 32.6
      +/- 2.4, and 0.01 pmol/microg DNA for dopamine, 6-hydroxydopamine, and control
      incubations, respectively, representing a 520- to 3260-fold increase in the level
      of this base oxidation product. The use of specific chelators and catalase
      demonstrated that the reduction of Cu2+ to Cu1+ and the formation of a peroxide
      plays an important role in the activation of dopamine and 6-hydroxydopamine to
      form adducts and oxidative base damage. Our results suggest that the oxidation of
      dopamine by transition metals present in the brain may lead to the formation of
      both DNA adducts and oxidative base damage in dopaminergic cells. We propose that
      these processes may contribute to the observed loss of dopaminergic neurons in
      patients with Parkinson's disease.

PMID- 9270071
TI  - Chronic nicotine treatment differentially regulates substance P and tyrosine
      hydroxylase immunoreactivity in substantia nigra ipsilateral to a unilateral
      lesion.
AB  - The present study was carried out with a variety of neuroanatomical techniques to
      investigate the consequences of chronic continuous nicotine treatment (0.125 mg x
      kg(-1) x h(-1), s.c., 14 days) on the lesion-induced effects of a partial meso
      diencephalic hemitransection. Both the striatonigral substance P (SP) and the
      nigrostriatal dopamine (DA) pathways were studied. The lesion-induced
      degenerative changes were most pronounced in the lateral parts of the ipsilateral
      substantia nigra and striatum. We have previously demonstrated that chronic
      nicotine infusion counteracts the lesion-induced loss of nigral tyrosine
      hydroxylase (TH) immunoreactive/Nissl stained DA neurons. The main finding of
      this study is that this phenomenon also involves changes in the striatonigral
      pathways. Thus, nicotine induced a disappearance of SP immunoreactive nerve
      terminals in substantia nigra pars compacta on the lesioned side, while it was
      again shown to counteract the lesion-induced disappearance of nigral TH
      immunoreactivity in the same animals. These data are interpreted on the basis of
      previous electrophysiological findings, where nicotine under similar experimental
      conditions counteracted the lesion-induced increase in burst firing in vivo in
      nigral dopamine neurons. Taken together these results indicate that nicotine may
      act by a reduced SP excitatory input to the nigral DA cells, which rescues them
      from dying. It is likely that the surviving cells are functional, since increased
      extracellular striatal DA levels have been observed after nicotine treatment
      ipsilateral to the lesion in a previous microdialysis experiment in vivo. These
      findings might contribute to the development of new neuroprotective therapies for
      patients suffering from neurodegenerative disorders such as Parkinson's disease.

PMID- 9270072
TI  - Microglia responses in the CNS following sciatic nerve transection in
      C57BL/Wld(s) and BALB/c mice.
AB  - The present study employed C57BL/Wld(s) mice to investigate whether a delay in
      microglia reaction would occur similar to the delay that occurs in macrophage
      response after sciatic neurectomy. The results were compared with control BALB/c
      mice. The observations showed that in both strains of mice there was no delayed
      microglia response around lesioned motoneurons and around the central processes
      of the dorsal root ganglion cells after sciatic neurectomy in the adult. The
      increased Mac-1 staining appeared as early as 1 day postoperation (dpo). This
      indicates that microglial cells and macrophages respond to different signals
      generated by neurectomy. In both strains of mice, the number of microglia in the
      neonate was much less than that in the adult and the increase in Mac-1 staining
      was detectable only at 3 dpo in both strains of mice. A significant loss of
      motoneurons was detected after sciatic neurectomy in the neonate. However, there
      were no significant differences in the mean percentages of motoneuron loss
      between the two strains of mice at 5, 10, and 15 dpo. It is surmised that the
      lack of an adequate number of mature microglia in the neonates and their tardy
      expression of CR3 antigenicity may contribute to the motoneuron loss.

PMID- 9270073
TI  - Estrogen regulates neurofilament gene expression in adult female rat dorsal root
      ganglion neurons.
AB  - Recently, adult female dorsal root ganglion (DRG) neurons were shown to express
      the estrogen receptor gene and to bind estrogen. This gene expression and binding
      is hormone dependent. Moreover, in a subpopulation of DRG neurons, the estrogen
      receptor is colocalized with high-affinity (trkA) and low-affinity (p75NGFR)
      receptors for nerve growth factor (NGF). In this NGF-responsive subpopulation of
      DRG neurons, estrogen regulates expression of the NGF receptor genes and may
      increase the sensitivity of these cells to the neurotrophin. The present study
      tested the hypothesis that neurofilament gene expression, which is regulated by
      NGF in these cells, is dependent on hormone status. In this study, ovariectomized
      (OVX) rats received either long-term physiological estrogen (conjugated
      estrogens; Premarin, Wyeth-Ayerst) replacement (low dose) or 10 times
      physiological levels (high dose). Quantitative in situ hybridization with an RNA
      probe for the 68-kDa neurofilament mRNA revealed a significant dose-dependent
      effect of Premarin on DRG neurofilament gene expression. In OVX animals receiving
      low-dose Premarin replacement therapy the mean steady-state 68-kDa mRNA level was
      as high as 4 times that of untreated OVX rats. High-dose therapy increased the
      mean 68-kDa neurofilament steady-state mRNA level to as much as six-fold that
      observed in untreated OVX animals. The estrogen-dependent upregulation of
      neurofilament gene expression appeared to occur in all DRG neurons, rather than
      in a subpopulation of those cells. These data suggest an important role for
      estrogen in the maintenance and function of primary sensory neurons. Whether
      estrogen directly regulates neurofilament gene expression or indirectly regulates
      it by increasing DRG neuronal sensitivity to neurotrophins or other growth
      factors remains to be determined.

PMID- 9270074
TI  - Influence of distal nerve segment volume on nerve regeneration in silicone tubes.
AB  - The influence of a volume of a distal nerve segment upon nerve regeneration in an
      8-mm gap created within a silicone tube was examined. The rats were randomly
      divided into four groups. Each group had 5 mm, 1 mm, or a half volume of 1-mm
      nerve segment (a nerve piece of 1 mm transected longitudinally) inserted into the
      distal end of a silicone tube of 11 mm. The empty group without a nerve segment
      was used as control. Diameters of regenerated cylindrical structure between the
      nerve ends in the silicone tube were measured under an operation microscope and
      myelinated axon diameter, myelinated axon density, myelin sheath width, and ratio
      of myelinated axon area to total cross sectional area were measured using the
      transverse sections at the midpoint of the silicone tube at 6 weeks after
      surgery. Although there was a significant difference in all of those parameters
      between the control group and any of the remaining three groups, no significant
      difference was found between any pair of these three groups. The results of this
      study indicated that the degree of nerve regeneration does not correlate with the
      volume of a distal nerve segment and even a very small piece can play an
      important role in supporting regenerating nerve beyond a definitive gap.

PMID- 9270075
TI  - Attenuation of oxidative neuronal necrosis by a dopamine D1 agonist in mouse
      cortical cell cultures.
AB  - Events which lead to an increase in intracellular free radicals induce necrotic
      cell death of cultured cortical neurons. In the present study, we report that
      treatment with 1 microM (+/-)-SKF-38393 hydrochloride, a selective D1 agonist, as
      well as 100 microM trolox, a lipophilic vitamin E analogue, significantly
      prevented oxidative-related necrotic cell death following exposure to 10 microM
      Fe2+ or 1 mM buthionine sulfoximine, an inhibitor of gamma-glutamylcysteine
      synthetase. The neuroprotective effect of (+/-)-SKF-38393 hydrochloride was
      partially reversed by addition of (+/-)-SKF-83566 hydrochloride, a selective D1
      antagonist. Quinelorane dihydrochloride, a selective D2 agonist, did not
      influence free radical neurotoxicity. Interestingly, inclusion of (+/-)-SKF-38393
      hydrochloride or quinelorane dihydrochloride did not attenuate apoptotic cell
      death of cortical neurons deprived of serum. The present study provides evidence
      that (+/-)-SKF-38393 hydrochloride attenuates oxidative neuronal necrosis, which
      has unique therapeutic potential for the treatment of various neurodegenerative
      diseases linked to oxidative stress.

PMID- 9270076
TI  - Asymptomatic cerebrovascular damages in essential hypertension in the elderly.
AB  - To investigate the underlying mechanisms of asymptomatic cerebrovascular damage,
      the diurnal change in blood pressure was evaluated in hypertensive patients with
      silent cerebral infarction (SCI). Sixty elderly hypertensive patients (age > or =
      60 years) were matched with 40 middle-aged patients (age < or = 59 years) for sex
      and left ventricular mass index (LVMi). Lacunar lesions were evaluated by
      magnetic resonance imaging as SCI. The presence and the severity of SCI increased
      with age. In the middle-aged group, the presence of SCI was significantly related
      to 24-h blood pressure and LVMi evaluated by echocardiography. In elderly
      patients, the presence of SCI had no relationship with 24-h blood pressure or
      LVMi. The lowest level of nocturnal diastolic blood pressure showed a J-shaped
      relationship with the incidence of SCI in the elderly patients. These findings
      indicate that the hemodynamic characteristics underlying the development of SCI
      differ between middle-aged and elderly hypertensive patients. A different
      approach to the treatment of hypertension in the elderly appears necessary.

PMID- 9270077
TI  - Influence of nighttime blood pressure on left atrial size in uncomplicated
      arterial systemic hypertension.
AB  - The aim of the study was to determine the relations of 24-h blood pressure (BP)
      and its different phases with left atrial size. A total of 130 subjects (mean age
      46 years) not taking cardiac drugs were studied by M-mode and Doppler
      echocardiography and ambulatory BP recording. Subjects (excluding those with
      coronary artery or valvular heart disease, heart failure, or diabetes) were
      classified into two groups: 25 normotensives and 105 hypertensives (history of
      antihypertensive treatment and office diastolic BP > 90 mm Hg). The two groups
      were comparable in terms of sex, age, and heart rate, whereas body mass index, (P
      < .01), office BP, average 24-h BP, and average daytime and nighttime BP (all P <
      .00001) were higher in hypertensives. Hypertensives also had increased left
      atrial dimension, left atrial dimension/aortic root ratio (both P < .001), and
      left ventricular mass (LV) indexed for height (P < .0001). Positive correlations
      of left atrial dimension were found with office BP, average 24-h, average daytime
      and nighttime systolic and diastolic BP, LV mass index, and Doppler-derived E/A
      ratio. In a multivariate model that included potentially confounding factors,
      only body mass index (standardized beta coefficient = 0.41, P < .00001), average
      nighttime diastolic BP (beta = 0.33, P < .00001), and male sex (beta = 0.18, P <
      .01) were independent predictors of left atrial size in the pooled population. In
      conclusion, left atrial size is more closely related to ambulatory, rather than
      office, BP measurements, and high average nighttime BP is a powerful marker of
      left atrial enlargement in arterial hypertension.

PMID- 9270078
TI  - Increased prevalence of cardiac arrhythmias and transient episodes of myocardial
      ischemia in hypertensives with left ventricular hypertrophy but without clinical
      history of coronary heart disease.
AB  - To evaluate the behavior of cardiac arrhythmias (CA) and transient episodes of
      myocardial ischemia (TEMI), in relation to the circadian pattern of blood
      pressure in patients suffering from arterial hypertension, with or without
      echocardiographically ascertained left ventricular hypertrophy (LVH), we studied
      128 patients, 87 men (M) and 41 women (F), aging from 21 to 76 years, subdivided
      into two groups: Group I, including 66 patients with LVH (45 M and 21 F; mean age
      of 53.7 +/- 9.1 years; Group II, including 62 patients without LVH (42 M and 20
      F; mean age of 49.7 +/- 9.5 years). Office blood pressure (OBP) as well as
      nighttime ambulatory blood pressure (ABP) were higher in patients with LVH (P <
      .05 and P < .01). CA were present in a higher number of patients of Group I (P <
      .001): premature supraventricular beats (PSVB) 22.7 v 4.8%, supraventricular
      couplets (SVC) 36.4 v 16.1%, supraventricular tachycardia runs (SVT runs) 27.3 v
      12.9%, ventricular ectopic beats (VEB) 25.6 v 8.0%, ventricular couplets (VC)
      30.3 v 12.9%, ventricular tachycardia runs (VT runs) 12.1 v 3.2%. The absolute
      number of ectopic beats was also significantly higher in patients of Group I.
      Ventricular arrhythmias were significantly related to ASBP (r = 0.83, P < .01),
      to ADBP (r = 0.74, P < .01) and to heart rate (r = 0.87, P < .01) in patients of
      Group I. TEMI were more frequent in patients of Group I (73 v 41 episodes, 39.39%
      v 25.8% of patients, P < .01) and were related to ABP peaks. In fact, in both
      groups of patients all TEMI without heart rate increase and most TEMI with heart
      rate increase were registered between 6:00 and midnight, hours in which ABP
      values were higher. We conclude that hypertensives with LVH, but without clinical
      history of coronary heart disease, have a higher prevalence of ventricular
      arrhythmias and of transient episodes of myocardial ischemia in relation to the
      circadian pattern of ABP.

PMID- 9270079
TI  - Losartan attenuates myocardial ischemia-induced ventricular arrythmias and
      reperfusion injury in spontaneously hypertensive rats.
AB  - To assess the efficacy of losartan (2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H
      tetrazol-5-yl)biphe nyl-4-yl)methyl]imidazole, potassium salt), an angiotensin II
      receptor antagonist, on acute myocardial ischemia, 36 four-month-old
      spontaneously hypertensive rats were used. The animals underwent 45 min of left
      coronary artery occlusion and 1 h of reperfusion and were randomly assigned to
      control and losartan-treated groups (2, 5, and 10 mg/kg, intravenously). Losartan
      was administered 15 min before ischemia. Electrocardiograms (lead II) were
      monitored continuously throughout the experiment. To assess the anti-infarct
      effect of losartan, the area at risk was determined by methylene blue dye and the
      infarct size was determined by nitroblue tetrazolium chloride staining. The areas
      of risk and infarct were measured by computerized planimetry. Results
      demonstrated that the low and intermediate doses (2 and 5 mg/kg) of losartan
      significantly decreased the incidence of ventricular fibrillation and mortality
      during the ischemic period induced by left coronary artery occlusion. However, a
      significant reduction in infarct size, calculated as a percentage of the area at
      risk, was noted in all three losartan-treated groups (control: 41.5% +/- 5.2%,
      losartan, 2 mg/kg: 11.2% +/- 5.8%, 5 mg/kg: 8.5% +/- 2.7% and 10 mg/kg: 13.7% +/-
      1.6%). The results suggest that losartan may be useful in the treatment of
      ventricular arrhythmias induced by acute myocardial infarction and attenuation of
      reperfusion injury in hypertension.

PMID- 9270080
TI  - Renal depressor mechanisms of physical training in patients with essential
      hypertension.
AB  - To clarify characteristics of the patients in whom exercise training lowers blood
      pressure and to elucidate the mechanisms by which exercise training lowers blood
      pressure, we evaluated 24-h blood pressure, glomerular filtration rate (GFR),
      renal blood flow (RBF), filtration fraction (FF), plasma renin activity (PRA),
      plasma aldosterone concentration (PAC), plasma norepinephrine concentration
      (PNE), and incremental area of insulin/glucose (sigmaI/sigmaG) during 75 g oral
      glucose tolerance test, and assessed arterial baroreceptor function (BSI) before
      and after a 3-week exercise training program (four 6-min sessions daily at 75%
      VO2 max). Patients were classified as responders (n = 15) if they showed
      statistically significant reduction in the multiple comparison of 24-h mean
      arterial pressure (MAP), or as nonresponders (n = 15) if they did not. Although
      there were no significant differences between responders and nonresponders in
      age, weight, MAP, GFR, RBF, RPF, FF, PNE, sigmaI/sigmaG, or BSI before exercise,
      renal vascular resistance (RVR; P < .05), PRA (P < .05), and PAC (P < .05) were
      significantly higher in responders than in nonresponders. The fractional
      excretion of sodium (FENa) (P < .05) were significantly lower in responders than
      in nonresponders. After exercise training, FF (P < .01), RVR (P < .05), PNE (P <
      .05) PRA (P < .01), and sigmaI/sigmaG (P < .05) decreased significantly only in
      responders. The decrease in MAP significantly correlated with the reductions in
      FF (r = 0.46, P < .05), PNE (r = 0.52, P < .01) and RVR (r = 0.40, P < .05).
      Thus, in patients who have higher RVR and PRA, exercise training lowered blood
      pressure in parallel to a reduction in RVR associated with decreases in
      sympathetic tone and improvement of insulin resistance. Our results suggest that
      exercise-induced changes in renal hemodynamics may contribute to the reduction in
      blood pressure in these patients.

PMID- 9270081
TI  - Preventive effect of iganidipine on renal and cerebral injuries in salt-induced
      hypertension.
AB  - Iganidipine, a new water-soluble calcium antagonist, was administered at a
      nonhypotensive dose (NHD) of 0.3 mg/kg/day, a moderate-hypotensive dose (MHD) of
      1.0 mg/kg/day, and a sustained-hypotensive dose (SHD) of 3.0 mg/kg/day to Dahl
      salt-sensitive (Dahl-S) rats fed a high-salt diet for 8 weeks. The effects on
      survival, and on renal and cerebral injuries, were then examined. Iganidipine
      completely prevented hypertensive death at the SHD and tended to increase the
      survival at the NHD and MHD. Iganidipine reduced glomerulosclerosis and renal
      arterial and tubular injuries in a dose-dependent manner. Iganidipine at the SHD,
      but not NHD or MHD, improved plasma creatinine, serum urea nitrogen, and
      glomerular filtration rate. Iganidipine at all doses examined increased the
      urinary prostaglandin (PG) I2 and PGE2, but not PGF2alpha or thromboxane B2, and
      decreased plasma angiotensin II (AII) level and renin activity. The renal
      glomerular, tubular, and arterial injuries were significantly correlated with
      blood pressure (r = 0.56 to 0.80) and plasma AII level (r = 0.50 to 0.71) but not
      with urinary prostanoids. Iganidipine also reduced the incidence of cerebral
      infarction. The infarction area was slightly and significantly correlated with
      urinary PGI2 (r = 0.42) and PGE2 (r = 0.41) but not with blood pressure or plasma
      AII. In conclusion, iganidipine prevented renal and cerebral injuries in Dahl-S
      rats. In addition to the reduced blood pressure, the reduction of plasma AII and
      the increase of vasodilatory prostanoids may also partially contribute to the
      renal and cerebral protective effects of iganidipine.

PMID- 9270083
TI  - Beneficial effect of alpha-blocker on hemorheology in patients with essential
      hypertension.
AB  - To assess the effect of antihypertensive therapy on hemorheology in essential
      hypertension, blood viscosity and red blood cell deformability were examined in
      45 patients with essential hypertension and 20 age-matched normotensive control
      subjects. Hypertensive patients were randomly assigned to monotherapy with five
      different antihypertensive drugs for 6 months and change of blood viscosity and
      red blood cell deformability were reexamined after the end of the monotherapy
      with each antihypertensive drug. Blood viscosity increased and red blood cell
      deformability decreased in hypertensive patients compared to normotensive control
      subjects. Monotherapy with each drug resulted in sufficient blood pressure
      control in all hypertensive patients. After the monotherapy with the alpha
      blocker, terazosin, blood viscosity decreased significantly at shear rates from
      22.5/sec to 450/sec, and red blood cell deformability, estimated by red blood
      cell filtration rate, increased by 15% (from 65 +/- 10 to 75 +/- 12 microL/sec, P
      < .05). The decrease in blood viscosity induced by alpha-blocker monotherapy may
      relate to an improvement of red blood cell deformability. It is possible that the
      treatment with alpha-blocker has a beneficial effect on the peripheral
      microcirculation due to an improvement of hemorheology in patients with essential
      hypertension.

PMID- 9270082
TI  - Is a series of blood pressure measurements by the general practitioner or the
      patient a reliable alternative to ambulatory blood pressure measurement? A study
      in general practice with reference to short-term and long-term between-visit
      variability.
AB  - We studied the reproducibility of a series of blood pressure measurements by
      general practitioner (GP) and patient in comparison with that of ambulatory blood
      pressure measurement (ABPM), with reference to short-term and long-term between
      visit variability using a prospective, comparative diagnostic study. The study
      group was 88 potentially hypertensive primary care patients (initial systolic
      blood pressure [SBP] between 160 and 200 mm Hg or with diastolic blood pressure
      [DBP] between 95 and 115 mm Hg). ABPMs were measured on 2 separate days (at a 6
      month interval). Two series of measurements by the doctor (at 1 to 6 month
      intervals), and the patient (at a 1 week interval) were measured. Mean
      differences and standard deviations of mean differences (SDD) between two
      successive series of measurements, and between two ABPMs were computed. The
      Wilcoxon signed-ranks test was used to compare these standard deviations. Mean
      initial office-blood pressures were 161 (SBP) and 102 (DBP) mm Hg. Long-term
      between-visit variability (measurements by GP) was larger than short-term between
      visit variability: SDDs were 16 v 11 mm Hg (SBP), and 10 v 8 mm Hg (DBP). The
      differences in average SBP and DBP between successive ABPMs and between
      successive series of office measurements by GP and home measurements by patient
      were not statistically significant. Mean differences between two series of
      measurements by GP and patient, and between two ABPMs, were 0 +/- 1 mm Hg. SDDs
      between successive ABPMs and series of measurements by GP and patient ranged from
      8 to 11 mm Hg (SBP), and were 6 mm Hg (DBP). No statistically significant
      differences were found between the SDDs of the studied measurement procedures
      (SBP and DBP). In our study the reproducibility of ambulatory blood pressure
      measurement was not found to be better than that of a series of four duplicate
      measurements by GP or patient. Long-term (6 months interval) between-visit
      variability was larger than the short-term (1 week interval) between-visit
      variability.

PMID- 9270084
TI  - Effects of alpha1-blockade on the forearm vascular resistance responses to lower
      body negative pressure in young borderline hypertensives.
AB  - To determine whether alpha1-blockade affects the forearm vascular resistance
      responses to lower body negative pressure (LBNP) in borderline hypertensives, six
      hypertensives (HTN; mean arterial pressure [MAP] = 109.9 +/- 1.7 mm Hg, mean +/-
      SE) and seven normotensives (NTN; MAP = 81.5 +/- 1.4 mm Hg) underwent exposures
      of LBNP at pressures of -10, -20, and -40 mm Hg during systemic alpha1-receptor
      blockade (BLK) and during placebo (PLA). Resting forearm vascular resistance
      (FVR) was greater in HTN than in NTN during PLA (34.8 +/- 5.4 v 17.5 +/- 3.1
      units; P < .05), but not during BLK (28.1 +/- 5.2 v 25.3 +/- 9.9 units). When
      expressed as a percentage of resting FVR, LBNP evoked an increased FVR (P < .001)
      that did not differ significantly between BLK and PLA in either group. FVR was
      higher (P < .001) in HTN than in NTN throughout both trials; at -40 mm Hg of LBNP
      during BLK, the increase in FVR was greater (P < .05) in HTN than in NTN (131 +/-
      42 v 48 +/- 15%). MAP (relative to resting) was maintained throughout LBNP during
      PLA but, at -40 mm Hg, was lower (P < .01) during BLK for both groups. HR was
      elevated in BLK and was increased at -40 mm Hg (P < .01) for each group in each
      trial. This increase was greater during BLK (P < .05). These data suggest that
      borderline hypertensives have a greater vasoconstrictor response to LBNP than do
      normotensives and alpha1-blockade does not appear to attenuate this response.

PMID- 9270085
TI  - Comparison of the combination of enalapril and a very low dose of
      hydrochlorothiazide with atenolol in patients with mild-to-moderate hypertension.
      Scandinavian Study Group.
AB  - The blood pressure lowering effect and tolerability of the angiotensin-converting
      enzyme inhibitor enalapril combined with a very low dose of hydrochlorothiazide
      (HCTZ) were compared with the selective betareceptor blocker atenolol in patients
      with mild-to-moderate hypertension. Three hundred seventy-four patients were
      randomized into a triple-blind, parallel, active-controlled 12-week study period
      comparing enalapril/HCTZ (20/6 mg) with atenolol (50 mg) after a 4-week placebo
      baseline period. Blood pressure (BP), clinical and laboratory safety, and
      metabolic laboratory variables were assessed. Enalapril/HCTZ as well as atenolol
      reduced both sitting and standing diastolic and systolic BP (P < .001), but
      enalapril/HCTZ had a more pronounced effect than atenolol on sitting systolic BP
      (P = .019); there was a trend toward more patients achieving target diastolic BP
      (<90 mm Hg, P = .053). No clinically important differences in safety and
      tolerability were observed.

PMID- 9270086
TI  - Rest and effort hemodynamic responses during prolonged treatment with felodipine,
      24-h blood pressure monitoring, and echocardiographic changes.
AB  - In an open study, 16 patients with moderate essential hypertension were treated
      with 5 or 10 mg felodipine daily for 3 months. Hemodynamic (HD) indices were
      assessed at rest and during isometric effort (IE) at days 0, 3 to 7, 30, 60, and
      90. Treatment efficacy was evaluated by ambulatory blood pressure monitoring for
      (ABPM) 24 h and divided between awake and sleep periods. Left ventricular mass
      (LVM) was determined before and at the end of treatment. Treatment normalized
      blood pressure (BP) in all patients (5 mg in 7 and 10 mg in 9). Systolic
      diastolic and mean arterial pressure (MAP) decreased significantly during the
      study (P < .01). The decrease in BP was significant on day 3 to 7 (P < .01) and
      tended to decrease further with treatment. Resting heart rate (HR) did not
      change. After 3 months systolic and diastolic pressure and MAP decreased
      significantly. Mean HR during ABPM differed between awake and sleep hours but did
      not change with treatment. When ABPM was divided into daytime and nighttime the
      awake BP decreased after 3 months (P < .01), but sleep measurements showed only a
      borderline decrease (P = .05). MAP after 3 months decreased in both awake and
      sleep periods. LV maximal and minimal dimensions did not change during treatment.
      Interventricular septum, posterior wall thickness, LVM, LVM/body surface area,
      and LVM/height tended to decrease, however this change was not significant.
      Hemodynamic measurements were measured at rest, at peak IE and posteffort. During
      treatment rest systemic vascular resistance (SVR) and MAP decreased, and there
      was no difference in ventricular ejection time, HR, and cardiac index. The
      increase in BP at IE was not prevented by treatment. After effort MAP decreased
      significantly and SVR tended to decrease in treated patients. Felodipine
      normalized resting BP in all patients. The main antihypertensive effect came at
      daytime and was less during sleep. No reflex tachycardia was seen during
      treatment. Echocardiographic measurements showed preservation of systolic and
      diastolic function and a tendency of decrease in LVM. Probably longer period of
      treatment is needed for clear-cut regression of LVM. Felodipine did not prevent
      the increase in BP and SVR during isometric effort, implying that normal
      cardiovascular reflexes are preserved during treatment.

PMID- 9270087
TI  - alpha- and beta-adrenoceptor blockade fail to prevent high sodium diet-induced
      left ventricular hypertrophy.
AB  - High sodium diet (HS, 8% NaCl) induces left ventricular hypertrophy (LVH) in
      normotensive rats without an increase in pressure or volume load or in resting
      cardiac sympathetic activity. HS may affect LV adrenoceptors density or affinity
      or their postreceptor pathways, thereby causing LVH. We therefore assessed the
      effects of HS with and without blockade of alpha1- or beta-adrenoceptors by
      terazosin or nadolol, alone or in combination, on resting hemodynamics, LV and
      right ventricular (RV) weights, and LV dimensions of male WKY rats. HS increased
      LV weight by 14% to 17%, and the ratio of LV wall thickness to radius by 18% to
      23%. Singly or in combination, the adrenoceptor antagonists did not prevent HS
      induced LVH, but instead aggravated it. The increased ratio of LV wall thickness
      to radius and of LV to RV were attenuated by terazosin or nadolol alone. Neither
      the resting LV peak-systolic or end-diastolic pressures nor the right atrial
      pressure was changed by HS, either alone or in combination with the blockers. The
      failure of chronic alpha1- or beta-blockade to prevent HS-induced LVH suggests
      that adrenoceptor activation is not important in evoking the LVH. However, the
      blockers shifted the LVH from a concentric to an eccentric form, suggesting an
      involvement of additional trophic factors during adrenoceptor blockade.

PMID- 9270088
TI  - Lack of association of polymorphisms of the angiotensin converting enzyme and
      angiotensinogen genes with nonfamilial hypertrophic or dilated cardiomyopathy.
AB  - Although several genes or genetic loci that are either responsible for or confer
      susceptibility to familial hypertrophic cardiomyopathy (HCM) or dilated
      cardiomyopathy (DCM) have been identified, genetic defects that underlie
      nonfamilial HCM or DCM remain to be characterized. An allelic association study
      for the angiotensin converting enzyme (ACE) and angiotensinogen genes has now
      been performed with 71 patients with nonfamilial HCM, 88 patients with
      nonfamilial DCM, and 122 healthy control subjects in the Japanese population. The
      distribution of ACE genotypes for an insertion/deletion (I/D) polymorphism in
      intron 16 did not differ significantly among control subjects and patients with
      HCM or DCM. Similarly, the distributions of angiotensinogen genotypes for
      methionine-235-threonine (M235T) and threonine-174-methionine (T174M)
      polymorphisms did not differ significantly among the three groups.
      Echocardiographic parameters that are indicators of the severity or progression
      of disease did not differ significantly among ACE I/D or angiotensinogen M235T
      and T174M genotypes in the two patient groups. Finally, no additive or
      synergistic effect of any combined genotypes or haplotypes of the ACE and
      angiotensinogen polymorphisms on the association with HCM or DCM was detected.
      Results indicate that the ACE I/D and angiotensinogen M235T and T174M
      polymorphisms are not related to HCM or DCM in the Japanese population, and that
      variants of these polymorphisms do not contribute to the genesis or progression
      of these cardiomyopathies.

PMID- 9270089
TI  - Inhibition of Na/K ATPase from rat aorta by two Na/K pump inhibitors, ouabain and
      marinobufagenin: evidence of interaction with different alpha-subunit isoforms.
AB  - Recently, we have shown that mammalian plasma cross-reacts with an antibody to a
      bufodienolide Na/K ATPase inhibitor, marinobufagenin. In rat aorta,
      marinobufagenin induced vasoconstriction via inhibition of the vascular smooth
      muscle Na/K pump, whereas ouabain had its predominant effect on pumps localized
      to nerve endings. Na/K ATPase inhibitory effects of ouabain and marinobufagenin
      were studied in two membrane fractions isolated from Fisher 344xBN rat thoracic
      aorta by sucrose density gradient centrifugation. One fraction contained
      predominantly the alpha-3 isoform of Na/K ATPase and represented membranes from
      the perivascular nerve endings (neuronal plasmalemma). The other membrane
      fraction, containing predominantly the alpha-1 isoform, was derived from the
      vascular smooth muscle sarcolemma. The IC50 for inhibition of the Na/K ATPase by
      ouabain and marinobufagenin were 2.6 nmol/L and 0.14 micromol/L in the neuronal
      plasmalemma, and 50 nmol/L and 2.1 nmol/L in sarcolemma, respectively. These
      results confirm the view that differential responsiveness to endogenous digitalis
      like factors is a functional feature of alpha isoforms of Na/K ATPase.

PMID- 9270090
TI  - Ambulatory blood pressure monitoring: how reproducible is it?
AB  - We tested the reproducibility of ambulatory blood pressure monitoring (ABPM) by
      the use of agreement plots. Thirty-two normotensive volunteers underwent ABPM on
      four separate days (interval 28 days), on the same typical weekday. Sleeping time
      was restricted to the ABPM nighttime subperiod from 11:00 PM to 7:00 AM. Twenty
      four-hour average values-both systolic and diastolic-daytime average values, and
      nighttime average values, as well as standard deviation (SD) values, were
      analyzed for differences (analysis of variance). Adaptation occurred from the
      first to the fourth ABPM, ie, average 24 h, daytime, and nighttime values were
      lower (-1 to -3 mm Hg) during the fourth recording than the first (P < .05 to P <
      .01). The agreement analysis showed a surprisingly high agreement among the four
      data sets (ie, differences from +/-2.54 to +/-5.92 mm Hg; +/-2 SD of the
      distribution). We concluded that reproducibility of ABPM seems excellent, but
      adaptation may occur, even in normotensive volunteers under research conditions.
      Caution must be paid before labeling a patient as hypertensive, because initial
      ABPM may yield higher values than later monitorings.

PMID- 9270091
TI  - Percutaneous transluminal angioplasty attenuates day-night difference in
      ambulatory blood pressure in renovascular hypertension.
AB  - To evaluate whether the circadian rhythm of blood pressure (BP) was altered in
      renovascular hypertension (RVH), ambulatory BP was monitored using a noninvasive
      recorder in nine patients with RVH attributable to fibromuscular dysplasia before
      and after percutaneous transluminal angioplasty (PCTA). The circadian rhythm of
      BP was assessed by the day-night difference in BP and by the single cosinor
      method. The day-night difference in BP before PCTA was significantly greater than
      in age- and sex-matched normotensive subjects (n = 9, P < .01) and patients with
      essential hypertension (n = 9, P < .05). PCTA decreased significantly the 24-h BP
      as well as plasma renin activity (P < .01). In the chronogram, the BP reduction
      after PCTA was evident especially during the day. Accordingly, the day-night
      difference in BP decreased significantly after PCTA (P < .01). In the cosinor
      analysis, the mesor and the percent amplitude of BP decreased significantly after
      PCTA (P < .01). In summary, circadian rhythm of BP was preserved or rather
      exaggerated in RVH. The stimulated renin angiotensin system in RVH possibly
      contributes to the altered circadian rhythm of BP primarily by elevating the
      daytime BP.

PMID- 9270092
TI  - Relationship between left ventricular diastolic function and atrial natriuretic
      factor in never-treated mild hypertensives.
AB  - Using digitized M-mode echocardiograms, we evaluated the relationship between
      plasma atrial natriuretic factor (ANF) and morphofunctional characteristics of
      the left ventricle (LV) in 24 mild hypertensive men, never treated, with normal
      renal function. For each subject we collected a blood sample for plasma ANF
      evaluation and, immediately after, we recorded the LV echocardiogram. All the
      patients had normal LV diastolic diameter and systolic function; LV hypertrophy
      was present in 10 patients, 7 of whom had left atrial enlargement, and 13
      patients had impaired LV diastolic function. ANF was similar between patients
      with and without LV hypertrophy, as well as between patients with and without
      left atrial enlargement, whereas ANF was significantly (P < .01) higher in
      patients with LV diastolic dysfunction than in patients with normal diastolic
      function. ANF was inversely correlated with both indices of diastolic function
      (peak lengthening rate and peak wall thinning rate), whereas it did not correlate
      with blood pressure, heart rate, end-systolic wall stress, and other LV
      parameters. In conclusion, from our results, ANF level in never-treated mild
      hypertensives is related neither to the degree of LV hypertrophy nor to the
      afterload, expressed as blood pressure or end-systolic wall stress, whereas it is
      mainly influenced by LV diastolic function: the diastolic impairment induces an
      increase in ANF level, probably through an increased atrial stretch.

PMID- 9270094
TI  - Pediatric Cardiology and the electronic literature.

PMID- 9270093
TI  - Relationship between the response to the angiotensin converting enzyme inhibitor
      imidapril and the angiotensin converting enzyme genotype.
AB  - Insertion (I)/deletion (D) polymorphism of the angiotensin converting enzyme
      (ACE) gene has been reported to be involved in various cardiovascular diseases.
      We investigated prospectively whether the response to the ACE inhibitor imidapril
      varied according to the ACE genotype or plasma ACE activity in Japanese
      hypertensive patients. The study population consisted of 57 hypertensive
      patients. After a 4-week observation period, imidapril was administered at a dose
      of 5 mg/day and blood pressure was measured every 2 weeks for 6 weeks. The plasma
      ACE activity in patients with the DD or ID genotype was significantly higher than
      that in patients with the II genotype. Neither the reduction nor the percent
      reduction in systolic blood pressure was significantly different between patients
      with either the DD or ID genotype and patients with the II genotype (DD or ID v
      II, 18.8 +/- 2.4 v 20.2 +/- 3.3 mm Hg; P = NS, 10.9 +/- 1.4 v 11.7 +/- 1.9%; P =
      NS, respectively). However, both the reduction and the percent reduction in
      diastolic blood pressure tended to be higher in patients with the II genotype (DD
      or ID v II, 7.9 +/- 1.2 v 12.4 +/- 2.2 mm Hg; P = .0669, 8.1 +/- 1.2 v 12.4 +/-
      2.2%; P = .0569, respectively). The reduction in diastolic blood pressure was
      inversely correlated with plasma ACE activity (r = 0.301, P = .0253). In
      conclusion, the response to imidapril in hypertensive patients is determined at
      least in part by the ACE genotype.

PMID- 9270096
TI  - PediHeart: pediatric cardiology and cardiac surgery on the Internet.

PMID- 9270097
TI  - Closure of atrial septal defects by transcatheter devices.

PMID- 9270098
TI  - Transcatheter closure of atrial septal defects by the "buttoned" device:
      complications and need for surgical revision.
AB  - Immediate and medium-term experience with transcatheter closure of a secundum
      atrial septal defect by the "buttoned" device in seven patients is reported.
      Complications occurred in two patients during the procedure. In one patient with
      complications, the occluder was partly released in the right atrium. All efforts
      to correct its position were unsuccessful and caused considerable deformation of
      the device, which had to be removed surgically. In the other patient with
      complications, disconnection of the occluder and counteroccluder occurred
      immediately after removal of the loading wire. Both parts were retrieved by
      catheter. Five patients had uneventful closure of the atrial septal defect. On
      follow-up, however, displacement of the device towards the mitral valve was
      observed in two patients, which caused mitral regurgitation. Surgical removal of
      the device and repair of the mitral valve was necessary in both patients. Two
      years after the procedure, the atrial septal defect was closed completely in two
      of the remaining three patients and a small residual defect persisted in one
      patient.

PMID- 9270099
TI  - Ablation of atrial insertion sites of left-sided accessory pathways in children:
      efficacy and safety of transseptal versus transaortic approach.
AB  - Left-sided accessory pathways are a common substrate for supraventricular
      tachycardias in children. A transseptal approach to catheter ablation has been
      primarily advocated in this population because of concerns regarding vascular
      injury, aortic, and mitral valvular damage using the transaortic approach via
      retrograde femoral arterial cannulation. However, the transaortic approach is
      simpler and may be less time consuming. We, therefore, compared the efficacy and
      safety of the transseptal vs the transaortic approach in 49 consecutive pediatric
      patients. In both groups, the atrial insertion site of the accessory pathways was
      targeted. Postprocedure two-dimensional and Doppler echocardiograms were obtained
      in all patients. The transseptal and transaortic groups were similar in age (15.8
      +/- 1.6 vs 13.5 +/- 3.6 p NS), manifest vs concealed (9/5 vs 20/15), and number
      of radiofrequency lesions (4 vs 6). Fluoroscopy time was significantly shorter in
      the transaortic group (33 vs 58 min, p < 0.05). The only evident complications
      were mild mitral regurgitation seen in two patients (one in each group). Two
      patients in the transseptal group had recurrence of tachycardia on follow-up and
      were successfully ablated by the transaortic method. In this series from a single
      center, a transaortic approach to ablation of left-sided accessory pathways in
      children older than 4 years was as effective as a transseptal approach.

PMID- 9270100
TI  - Cost-effectiveness analysis of stents, balloon angioplasty, and surgery for the
      treatment of branch pulmonary artery stenosis.
AB  - Branch pulmonary artery stenosis is a common problem in pediatric cardiology.
      Treatment has included surgery, balloon angioplasty, and balloon expandable stent
      placement. It was the purpose of this investigation to demonstrate the cost
      effectiveness of each of these modes of treatment. From 1983 to 1994 there were
      30 patients admitted for treatment of branch pulmonary artery stenosis only. Data
      included age at procedure, sex, primary diagnosis, acute and intermediate term
      success, and complications. Acute success was defined by results at the end of
      the procedure where intermediate term (IT) success was defined by results at
      follow-up. Success of a procedure was defined by at least one of the following:
      an increase in vessel diameter by >/=50% of predilation diameter, a decrease in
      right ventricular to left ventricular or aortic systolic pressure ratio by
      >/=20%, or a decrease in peak to peak pressure gradient by >/=50%. The procedure
      was considered a failure if the previously mentioned criteria were not met or if
      the patient required a second procedure for the same stenosis. The expense of the
      procedure (estimated by using the patient charges) were collected from the time
      of the procedure until December 1994. Because of differing lengths of follow-up,
      the patients were analyzed separately for procedures and outpatient charges. The
      total charges were corrected to 1994 dollars using the Medical Consumer Price
      Index. Thirty patients had 46 separate procedures (12 patients had >1 procedure
      and 3 had >2 procedures). There were 13 surgeries, 13 balloon angioplasties, and
      20 stents. Stents were the most successful (90% acute and 85% IT), but were not
      statistically superior to surgery (62% acute and IT). Balloon angioplasty was
      significantly less successful as compared with stents (31% acute and 23% IT), and
      was not statistically different from surgery over the acute and intermediate
      term. The charge data showed balloon angioplasty was the least expensive followed
      by stents and then by surgery. The average total charges per procedure, including
      outpatient charges, were: surgery $58,068 +/- $4372 (standard error), balloon
      $21,893 +/- $5019, stents $33,809 +/- $3533 (p < 0.001); excluding outpatient
      charges: surgery $52,989 +/- $3649, balloon $15,653 +/- $1691, and stents $29,531
      +/- $2241 (p < 0.001). Average total charges per patient, including all procedure
      types and grouped by initial procedure, were: surgery $53,707 +/- $6388, balloon
      $50,040 +/- $8412, and stent $34,346 +/- $3488 (p = 0.047). Stents were at least
      as effective as surgery and were more effective than balloon angioplasty in both
      acute and intermediate term follow-up. Balloon angioplasty was least expensive
      per procedure but was also least effective. Therefore, intravascular balloon
      expandable stents are the most cost-effective means available in the treatment of
      branch pulmonary artery stenosis.

PMID- 9270101
TI  - Evaluation of magnetic resonance imaging in coarctation of the aorta: the
      importance of multiple imaging planes.
AB  - Coarctation of the aorta can be evaluated reliably and noninvasively by magnetic
      resonance imaging. However, the value of different imaging planes in the
      evaluation of restenosis or aneurysm has not previously been studied. Our purpose
      was to study the relative sensitivity for oblique coronal and oblique
      parasagittal magnetic resonance imaging to detect restenosis or aneurysm
      formation in children following surgical repair or balloon angioplasty of
      coarctation of the aorta. The study included magnetic resonance imaging studies
      in 27 children. Each exam included ECG gated, spin-echo imaging in oblique
      coronal and oblique parasagittal planes. Recoarctation was defined as a greater
      than 50% narrowing of the aorta. Aneurysms were defined as focal dilatation of
      the aorta in the region of coarctation 20% or greater than the adjacent aortic
      diameter. Recoarctation was detected in 11 children, but in both views in only
      five children. Aneurysms were detected in 15 children, but in both views in only
      three children. Recoarctation and aneurysm detection were both statistically more
      likely to be detected if oblique coronal and oblique parasagittal views were
      obtained, indicating that multiple imaging planes are necessary to completely
      evaluate magnetic resonance imaging of coarctation.

PMID- 9270103
TI  - Determinants of aerobic capacity during exercise following complete repair of
      tetralogy of Fallot with a transannular patch.
AB  - Exercise capacity and the causes of its limitation following repair of tetralogy
      of Fallot have been studied in heterogeneous populations. Study populations have
      been grouped together regardless of the type of repair and residual hemodynamic
      abnormalities. To better understand the factors limiting aerobic exercise
      capacity in patients repaired with a transannular patch, 37 patients with a
      transannular patch and no residual pulmonary stenosis underwent resting
      spirometry and treadmill exercise testing. Maximal oxygen consumption and oxygen
      consumption at anaerobic threshold were measured in all patients to assess
      aerobic capacity. Patients were subdivided by gender. Resting spirometry
      measurements tended to be lower in both genders compared to healthy controls but
      did not correlate with any measurement of aerobic capacity. Maximal oxygen
      consumption and anaerobic threshold were significantly less in the female than
      the male population. A quadratic relation between maximal oxygen consumption and
      age at exercise testing existed for both genders but peaked at an earlier age and
      was significantly less in the female population. There was a significant negative
      correlation between maximal oxygen consumption and echocardiographically
      estimated right ventricular inflow volume index in the female population only.
      These data suggest that in patients with tetralogy of Fallot repaired with a
      transannular patch aerobic capacity is limited primarily by cardiac function, but
      that gender differences are due to noncardiac causes.

PMID- 9270104
TI  - Exercise performance following repair of hypoplastic left heart syndrome: A
      comparison with other types of Fontan patients.
AB  - Reports of exercise performance after Fontan surgery for hypoplastic left heart
      syndrome (HLHS) are lacking. We compared the exercise performance of total
      cavopulmonary connection type (TCPC) of Fontan subjects with HLHS (group 1, n =
      7) to those not requiring a Norwood procedure having a systemic right ventricle
      (group 2, n = 6) or a systemic left ventricle (group 3, n = 8). The subjects
      underwent assessment of resting pulmonary mechanics followed by maximal exercise
      testing with a bicycle or treadmill protocol. ECG, oxygen consumption, and carbon
      dioxide production were measured continuously. There was not a significant
      difference seen between HLHS and the comparison groups for the following
      parameters: maximum heart rate, maximum oxygen consumption, respiratory exchange
      ratio, breathing reserve, and arterial oxygen saturation at rest or exercise.
      Exercise performance in the TCPC type of Fontan patients was comparable
      regardless of ventricular morphology or surgical approach.

PMID- 9270106
TI  - Diagnostic and perinatal management of fetal extrasystole.
AB  - Fifty fetuses referred to the Polish Mother's Memorial Hospital for fetal
      echocardiography between January 1, 1991 and June 1, 1995 were evaluated. The
      mean fetal gestational age at the time of diagnosis of arrhythmia was 34.1 weeks,
      and the mean gestational age at the time of delivery was 38.7 weeks. Checkup
      echocardiographic examinations were performed every 10-14 days, for a mean 2.4
      studies per fetus. In most cases (48/50, 96%), premature atrial contractions were
      present during the first echocardiography examination. The fetal heart study was
      normal in 30 cases; in 7 (14%) there was tricuspid valve regurgitation, in 7
      (14%) an atrial septal aneurysm, in 4 congenital heart defects, in 1 myocardial
      hypertrophy, and in 1 disproportion in the four-chamber view. Of the 50 fetuses,
      43 underwent regular echocardiographic monitoring alone; in 7 cases, based on the
      presence of additional echocardiographic findings, pharmacotherapy was applied
      (digoxin, verapamil, or both). Three neonates died after delivery owing to
      malformations in two cases (one critical aortic stenosis, one spina bifida plus
      hygroma colli) and due to myocarditis in one case. In six of seven newborns
      treated in utero, myocarditis was diagnosed after birth (including the one with
      neonatal demise). Most of the newborns were in good condition after birth, their
      mean Apgar score being 8.6 and the mean birth weight 3259 g. We concluded that
      most extrasystoles represent an isolated anomaly, not affecting the fetal
      condition. Their presence should not influence the obstetric care and may require
      only echocardiographic monitoring. In most of our cases the premature
      contractions subsided after birth, although sometimes they preceded fetal
      supraventricular tachycardia or appeared after congenital myocarditis.

PMID- 9270107
TI  - Syncope in childhood.
AB  - The records of 108 children, ages 2 to 19 years (mean age 11.3 years), who were
      referred to the pediatric neurology and pediatric cardiology clinics for syncope,
      were reviewed. Sixty-six cases were identified retrospectively, and 42
      prospectively. Syncope was defined as transient and complete loss of
      consciousness with no etiology determined at the time of presentation. The mean
      follow-up was 2.0 years. In 27 cases (25%), an etiology for syncope was found,
      including migraines in 12 cases (11%), seizures in 9 cases (8%), and cardiac
      arrhythmias in 6 cases (6%). All other cases were classified as vasovagal
      (neurocardiogenic). The past medical history, family history, clinical features
      of each syncopal episode, and diagnostic tests of each subject were correlated to
      final diagnosis. No clinical or historical features reliably distinguished
      children with vasovagal syncope from those with other etiologies. Children
      referred for the evaluation of syncope have a significant incidence of serious
      but treatable disorders, which should be actively sought.

PMID- 9270108
TI  - Ductus arteriosus in premature infants beyond the second week of life.
AB  - Persistent patency of the ductus arteriosus (PDA), common in premature infants,
      is associated with severe respiratory distress. The likelihood and significance
      of finding PDA in premature infants beyond the second week of life is unknown. We
      retrospectively analyzed all echocardiograms obtained between 1987 and 1992 on
      infants <35 weeks' gestational age. Of 446 echocardiograms 77 were obtained from
      infants >/=14 days. Of the 77 infants, 17 (22%) were found to have PDA (group 1)
      and the remainder did not (group 2). Forty-eight infants had been diagnosed as
      having PDA prior to 14 days of age. Of these infants, 16 were from group 1. Thus
      only 1/17 (6%) infants diagnosed as having PDA after 2 weeks did not have a
      history of PDA. The presence of PDA after 2 weeks did not relate to duration of
      oxygen therapy, ventilator therapy, or hospital stay. Furthermore, late closure
      of PDA in a subgroup of 11 infants did not appear to affect these parameters. It
      was concluded that premature infants beyond the second week of life are unlikely
      to have PDA if PDA had not been diagnosed during the first 14 days. Closure of
      PDA beyond the second week may not improve the infant's respiratory status.

PMID- 9270109
TI  - Coarctation of the left pulmonary artery: effects on the pulmonary vasculature of
      infants.
AB  - At autopsy, two infants had unsuspected coarctation of the left pulmonary artery
      (CoLPA), which was produced by an extension of ductal tissue into the wall of the
      left pulmonary artery. The first case, a 4-month-old girl, also had a ventricular
      septal defect and an anomalous branching pattern of the innominate arterial
      trunk. Pulmonary arterial hypertensive changes were noted in the right lung. In
      contrast, the left lung showed thin-walled pulmonary arteries. The second case, a
      term female newborn, had exhibited severe unexplained respiratory distress since
      birth. Histologic sections of the right lung showed dilated pulmonary arteries
      with thinned media, whereas the left lung showed a persistent fetal arterial
      pattern. It is believed that the peripheral pulmonary arterial changes are age
      dependent and associated with asymmetric blood flow between the right and left
      pulmonary arteries. CoLPA is a rare pulmonary artery defect, and early diagnosis
      of this abnormality is important.

PMID- 9270111
TI  - Congestive heart failure with tetralogy of Fallot relieved by an aortopulmonary
      shunt.
AB  - Congestive heart failure occurring in unoperated patients with otherwise
      uncomplicated tetralogy of Fallot (TF) is rare. We report the case of a boy who
      was first diagnosed as having TF when he presented at age 3 years with hypoxia
      and heart failure. Heart failure improved following an aortopulmonary shunt. We
      attributed his heart failure to cardiomyopathy associated with severe hypoxia. We
      believe that this report is the first one that attributes heart failure to
      hypoxia in an unoperated patient with tetralogy of Fallot.

PMID- 9270113
TI  - Aberrant left coronary artery arising from the right sinus of Valsalva with a
      right coronary arteriovenous malformation.
AB  - An 11-year-old boy presented with myocardial ischemia and was found to have an
      aberrant left main coronary artery from the right sinus of Valsalva coursing
      between the aorta and pulmonary artery, as well as a small arteriovenous
      malformation from a right atrial branch of the right coronary artery to the right
      atrium. Distinctive echocardiographic findings were supported by angiographic and
      magnetic resonance imaging studies. Treadmill and scintigraphic stress testing
      were normal. Corrective surgery was accomplished by a modified technique to
      unroof the intramural proximal course of the left coronary artery, without
      postoperative complications. The anatomy and pathophysiology of this rare
      coronary lesion are reviewed.

PMID- 9270114
TI  - Dilated endocardial fibroelastosis: unusual late finding with congenital hydrops.
AB  - The case of a baby born with severe nonimmune hydrops fetalis in whom endocardial
      fibroelastosis was a late finding is reported. Left ventricular dimensions and
      systolic function were normal at presentation. After recovery from the hydrops,
      at 2 months of age, a dilated, poorly contracting left ventricle was documented
      and eventually led to the infant's death.

PMID- 9270116
TI  - Fatal rupture of an acquired aneurysm of the pulmonary artery: rare complication
      after surgical palliation of tricuspid atresia.
AB  - We report the case of a young woman who died from rupture of an aneurysmal
      dilatation of the left pulmonary artery. She suffered from tricuspid atresia type
      Ib and underwent a classic Glenn anastomosis at the age of 11 months; at 11 years
      a direct laterolateral anastomosis was constructed between the ascending aorta
      and the left pulmonary artery rather than a Fontan procedure for technical
      reasons. She subsequently developed severe pulmonary hypertension and an
      aneurysmal dilatation of the left pulmonary artery and was refused any further
      surgical correction.

PMID- 9270119
TI  - Versatility of immunohistochemical reactions: comprehensive survey of detection
      systems.
AB  - The field of immunohistochemistry comprises histological methods enabling
      detection of tissue antigens via specific antibodies. Although all these
      techniques take an advantage of a large specificity of antibody to a particular
      tissue antigen there are many different approaches for enhancement and
      visualization of the signal. The aim of the present review article was to briefly
      outline the historical milestones that made the rapid progress of this discipline
      possible and give a comprehensive survey of immunohistochemical methods
      applicable to biomedical research. The survey starts with a description of the
      direct immunohistochemical method and then pays attention to a huge number of
      indirect methods. For better explanation of principles of individual techniques,
      the text is accompanied with graphical schemes. The highest attention is given to
      immunohistochemical methods that are most generally used, i.e. enzyme anti-enzyme
      complex methods (e.g. Peroxidase Anti-Peroxidase/PAP/ or Alkaline Phosphatase
      Anti-Alkaline Phosphatase /APAAP/) and methods based on avidin-biotin
      interactions (Bridged Avidin-Biotin/BRAB/, Avidin-Biotin Complex /ABC/, Labelled
      Avidin-Biotin/LAB/). Nevertheless, the principles of other immunohistochemical
      methods like two- or three-step indirect immunohistochemical methods, methods
      based on protein A-antibody interaction and Hapten Antibody Anti-Hapten method
      (HAAH), are also thoroughly characterized. Usefulness of each method for a
      specific utilization, its advantages and disadvantages are mentioned and compared
      with the latest immunohistochemical techniques, like Multi-Layered Peroxidase
      Labelled Antibody (MLP) and water soluble polymer conjugates, e.g. Enhanced
      Polymer One-Step staining (EPOS) or EnVision. The last paragraphs are devoted to
      immunohistochemical amplification systems (Catalyzed Signal Amplification/CSA/
      and label anti-label) that dramatically increase sensitivity of detection systems
      and enable to compare sensitivity of immunohistochemical methods with the most
      sensitive methods of molecular biologists.

PMID- 9270118
TI  - Corrected transposition of the great arteries with isolated aortic coarctation:
      In utero echocardiographic diagnosis.
AB  - Physiologically corrected transposition of the great arteries (cTGA), defined by
      discordant atrioventricular and ventriculoarterial connections, is an uncommon
      congenital cardiac malformation. It rarely exists without associated cardiac
      anomalies, the most common of which are ventricular septal defect, pulmonary
      outflow obstruction, tricuspid valve (systemic) deformity, and rhythm
      disturbances. Conversely, hypoplasia of the systemic ventricle and systemic
      inflow or outflow obstructions have seldom been reported, although their
      recognition may significantly influence surgical repair and the patient's
      prognosis. We report a case of cTGA with complete heart block, moderate
      hypoplasia of the systemic ventricle, and severe aortic coarctation that was
      echocardiographically diagnosed in utero at 30 weeks' gestation because of fetal
      growth retardation and persistent fetal bradycardia. After delivery the patient
      underwent epimyocardial pacemaker implantation and aortic coarctation repair at 2
      weeks of age. Unfortunately, the patient died on the seventh postoperative day
      because of systemic ventricular hypertrophy. Although it is well known that fetal
      echocardiography may reliably diagnose uncommon congenital cardiac malformations,
      to the best of our knowledge, this paper represents the first reported case of
      antenatal diagnosis of this complex anomaly.

PMID- 9270120
TI  - Multiple regression analysis of parameters of lipid and glycide metabolism in
      obese and lean genetically hypertensive Koletsky rats under long lasting
      terguride treatment.
AB  - Experiments were carried out in the genetically hypertensive obese rats of
      Koletsky type (SHR/N-cp) and in their lean siblings. Regression analysis was
      performed when plasma triglycerides was used as a dependent variable and plasma
      insulin, insulin binding to erythrocytes, basal plasma glucose tolerance data
      were used as independent variables. Coefficient determination (R2) as well as the
      tests of hypotheses of regression coefficients being zero were used to indicate
      which independent variables contributed the least in the explanation of dependent
      variable. This way we reduced the list of variables to give a simpler regression
      equation. In the control animals insulinemia was found to be dominant independent
      variable in all groups except SHR/N-cp obese females where the dominant
      independent variable was represented by the basal plasma glycaemia. Under the
      terguride treatment only in SHR/N-cp female rats the dominant independent
      variable remained the same as in controls. In the other groups the dominant
      independent variable was different in relation to the control animals. Long
      lasting terguride treatment normalized hypertriglyceridemia only in SHR/N-cp
      obese females. Thus the data obtained by multiple regression analysis of
      parameters of lipide and glycide metabolism show the close relationship to
      alleviating effect of terguride in hypertriglyceridemia.

PMID- 9270121
TI  - The effect of reperfusion on plasma tumor necrosis factor alpha and C reactive
      protein levels in the course of acute myocardial infarction.
AB  - Severe acute response, the synthesis of human acute-phase proteins and the
      increase of plasma cytokines and adhesion molecules occur in patients in the
      course of acute myocardial infarction. We examined the plasma tumor necrosis
      factor alpha (TNF alpha), plasma creatinkinase (CK) and C-reactive protein (C-RP)
      levels in patients with acute myocardial infarction (AMI) in the course of 96
      hours. Venous blood samples were taken at 3-hour intervals during the first 48
      hours, and at 6-hour intervals during the next 48 hours. All patients were
      treated using thrombolytic therapy (streptokinase). Detection of the reperfusion
      was based on the method of measuring the time to achieve peak serum creatinkinase
      activity. The study was done on a group of 24 patients. Plasma levels of the
      parameters were compared between the group of patients with expected reperfusion
      versus the group of patients in which reperfusion is not suggested. The plasma
      TNF alpha level was elevated constantly without any significant peak. The mean
      plasma TNF alpha concentration was 46.8 pg/ml, SD 2.13, vs. normal level 4.35
      pg/ml, p < 0.001. The plasma TNF alpha level in the group of patients with
      reperfused coronary artery showed a significant decrease especially during the
      3rd and 4th day (the mean peak plasma TNF alpha concentration was 35.2 pg/ml, SD
      15.8, vs. 66.9 pg/ml, SD 38.3 pg/ml, p < 0.005). The plasma C-RP levels were
      elevated throughout the time of observation in the both groups. The elevation of
      the plasma C-RP levels was more significant in the group of patients without
      successful reperfusion (80.6 mg/ml, SD 31.2, the mean plasma C-RP level of the
      group of the patients with successful reperfusion was 45.7 mg/ml, SD 18.1, p <
      0.005). We conclude, that TNF alpha can play a role in the mechanisms of tissue
      injury. The successful reperfusion of coronary artery leads to significant
      decrease of plasma TNF alpha and C-RP levels.

PMID- 9270122
TI  - Contribution to technique of endarterectomy of the right coronary artery.
AB  - We present our technique of performing endarterectomy of coronary arteries by
      means of injecting cardioplegic solution into the plane of dissection of the
      endarterium. This simple and gentle technique in combination with manual
      endarterectomy helps in separation of the core far into the periphery of the
      diseased vessel and thus helps to perform revascularization in patients with
      diffuse atherosclerotic changes. During the last 6 years (1991-1996)
      endarterectomy in coronary revascularization was used in 116 cases (it was 5.7 %
      (116/2031) of all myocardial revascularization procedures). On right coronary
      artery endarterectomy was used in 82 patients. Mortality rate in our group of
      patients was 4.88 % (4/82) and perioperative myocardial infarction developed in
      4.88 % (4/82). According to our own experience with this technique of
      endarterectomy on right coronary artery we are convinced that in desperate
      patients with diffuse coronary artery disease our method can bring better and
      wider application of surgical treatment.

PMID- 9270123
TI  - To the history and evolution of hygiene and preventive medicine at the Faculty of
      Medicine of Charles University in Hradec Kralove.
AB  - In a dynamic sequence there has been presented longer than 50 years lasting
      history of the branch "Hygiene" (after the year 1989 joined with "Preventive
      Medicine") in the University Department of the same name of the Medical Faculty
      of Charles' University in Hradec Kralove since the year 1945 till today. The
      modern primary preventive medical field "Hygiene and Preventive Medicine" today
      not only covers the medical studies but, at the same time, represents a complex
      integrating general ecological approach to solving most of problems of public
      health, environmental one included. Ensuring the global good conditions for man
      during his permanently sustainable healthy living and development being the
      ultimate goal.

PMID- 9270124
TI  - Histopathological changes induced by environmental stress in common carp,
      Japanese coloured carp, European eel, and African catfish.
AB  - Histopathological changes caused by stress during catching and transport were
      examined in four fish species, the common carp (Cyprinus carpio), the Japanese
      coloured carp (koi, the coloured variant of the Asian carp, Cyprinus carpio
      haematopterus), the European eel (Anguilla anguilla), and the African catfish
      (Clarias gariepinus). In all species, the goblet cells of the gills and skin were
      decreased in number and slight detachment of the epithelium of the secondary gill
      lamellae was seen. Loss of goblet cells and detachment of the columnar epithelial
      cells were found in the intestinal mucosa of common carp and coloured carp. It is
      supposed that these lesions may affect ion transport and respiration in the gills
      and disturb normal intestinal function, thus serving as a starting point for
      different diseases.

PMID- 9270125
TI  - Cytogenetic effects of the herbicide chloridazon in cultured sheep lymphocytes.
AB  - The effect of in vitro exposure to the herbicide chloridazon on the induction of
      chromosome aberrations (CA) and sister chromatid exchanges (SCE) was studied in
      cultured sheep peripheral lymphocytes. A positive clastogenic effect was observed
      in chloridazon-treated cultures at a dose of 7 x 10(-4) M both in the presence
      and absence of the S9 fraction, but no significant increase of chromosome breaks
      was seen at lower doses (7 x 10(-6) M and 7 x 10(-5) M, respectively). A clear
      dose-dependence and significant differences were found in chloridazon potency to
      induce SCEs. Induction of cell cycle delays as compared to the controls was not
      observed.

PMID- 9270126
TI  - Characterisation of the swine swC1 antigen.
AB  - Some biochemical and functional characteristics of the swine swC1 antigen,
      determined by the use of the authors' swC1-specific monoclonal antibody (mAb) 335
      2, are reported. The molecular weight of the antigen was determined by
      immunoprecipitation. The swC1 antigen has 41 and approx. 15 kD components under
      reducing conditions. It is sensitive to proteolytic enzymes such as bromelain or
      trypsin, but not to papain. Phosphatidylinositol-specific phospholipase C
      treatment diminished the expression of swC1 on the surface of leukocytes. Cross
      linking of swC1 on the cell surface did not influence the proliferation of
      mitogen-activated mononuclear cells and had no mitogenic activity by itself.
      During 48 h of mitogen activation its surface expression did not change
      significantly. Possible relationships of swC1 to human CD antigens are discussed
      in the light of the results obtained.

PMID- 9270127
TI  - Serological findings obtained in cattle herds immunised with the Brucella
      melitensis Rev.1 and the B. abortus B19 vaccine in Mongolia.
AB  - To reduce the economic losses caused by Brucella abortus infection under the
      conditions of nomadic cattle breeding, more than half million cattle over 3
      months of age (excluding male animals) were immunised with the B. melitensis
      Rev.1 vaccine in 7 provinces of Mongolia in the first year of a programme (1987).
      In the second year, only heifer calves over 3 months of age, yearling animals not
      vaccinated in the first year, as well as heifers over 2 years of age and cows
      were vaccinated. The vaccine was administered subcutaneously at a dose of 5 x
      10(9) viable organisms. In co-operatives that had used the B. abortus B19
      vaccine, the existing vaccination programme was maintained, and all cattle over 3
      months of age (except male animals) were vaccinated with a dose of 5 x 10(10)
      viable organisms, using the same vaccination programme as in herds immunised with
      the Rev.1 vaccine. Before vaccination, two serological tests were carried out at
      an interval of 20-25 days to determine the incidence of Brucella infection. Serum
      samples were tested by the Rose Bengal test (RBT), serum agglutination test (SAT)
      and complement fixation test (CFT). An infection rate of 3.8-35% was found in the
      herds tested. Animals serologically positive for brucellosis were removed from
      the herds. Fifteen to 21 days after vaccination, blood samples were taken from
      10% of the animals in all immunised herds. The serum samples were tested by SAT
      and CFT to check the seroconversion rate. In herds immunised with the Rev.1
      vaccine 90% of the cows and 92.7% of the heifers were seropositive, while the
      seropositivity rate of B19-vaccinated cows and heifers was 68.8% and 89.7%,
      respectively. The serological status of the vaccinated animals was checked not
      only immediately after vaccination but also 12 months thereafter (in B19
      vaccinated cows also 24 months after vaccination). After Rev.1 vaccination,
      antibodies were present in 7% of the cows, 4.6% of the 3-year-old heifers, 3.1%
      of the 2-year-old heifers, and 1.6% of the 1-year-old animals. By comparison,
      13.2% of the cows vaccinated with the B. abortus B19 vaccine were serologically
      positive 2 years after immunisation. As regards the B19-vaccinated heifers, 7.9%,
      5% and 2.7% of the 3-year-old, 2-year-old and 1-year-old animals, respectively,
      were serologically positive even 12 months after vaccination.

PMID- 9270128
TI  - Role of the Danish pig production system in the success of infectious disease
      control: a review.
AB  - Pigs produced by the Danish system have played a dominant role on the
      international market for many years. A key factor in attaining that position was
      that the producers recognised the importance of animal health in market
      regulation and profit generation in due time. This paper reviews the factors
      that, through a close co-operation between the production and animal health
      sectors, have contributed to the stable market position of Danish pigs.

PMID- 9270129
TI  - Olive by-products in pig fattening.
AB  - The utilisation in pig fattening of diets with various proportions of dried olive
      cake, i.e., olive by-product resulting from centrifugal separation, was
      investigated in 60 Swedish Landrace x Large White crossbreds (30 castrates and 30
      gilts). The pigs were divided into three equal groups (10 + 10): two experimental
      groups, fed with a fodder mix containing 50 g/kg and 80 g/kg respectively of
      dried olive cake, and a control group, fed with the same mix but minus the cake.
      The experiment last 90 days. For the first 45 days the pigs were given the
      starter, and for the second 45 days the finisher, mix. Throughout the whole
      period, pigs in both experimental groups achieved greater average body mass and
      mass gain than the control animals. Concurrently, castrates in all three groups,
      became heavier and demonstrated greater mass gain than did the gilts. While
      supplied respectively with the finisher mix throughout the whole test period,
      pigs fed mixes with 50 g/kg of dried olive cake demonstrated significantly
      greater feed consumption than those fed without the cake and than those fed mixes
      with 80 g/kg of cake. While supplied with the starter mix, pigs fed mixes with 50
      g/kg of dried olive cake achieved the lowest feed conversion rate, whereas those
      supplied with the finisher mix achieved the highest. Throughout the entire period
      no significant differences were observed in feed conversion rate among pig
      groups.

PMID- 9270130
TI  - Comparison of indirect immunofluorescence (IIF) and enzyme-linked immunosorbent
      assay (ELISA) in detecting Babesia bigemina infection in cattle.
AB  - An indirect immunofluorescence test (IIF) and an enzyme-linked immuno-sorbent
      assay (ELISA) were standardised to investigate the prevalence of bovine
      babesiosis caused by Babesia bigemina in experimentally and naturally infected
      bovids. Both IIF and ELISA detected antibodies to B. bigemina 7 days after
      experimental infection with 87.5% and 100% sensitivity, respectively. The IIF
      results indicated that a titre greater than 1:64 was a reliable indicator of B.
      bigemina infection. Serological study of 214 serum samples collected from
      Boophilus microplus infested cattle from the State of Orissa revealed 33.6%
      overall seroreactivity by ELISA, whereas IIF recorded 9.4%. Both IIF and ELISA
      showed some degree of cross-reactivity between Indian (Izatnagar) and Mexican
      strains of B. bigemina.

PMID- 9270131
TI  - Some haematological and immunological parameters of farmed deer in Hungary.
AB  - A haematological survey of farmed fallow deer (Dama dama) and red deer (Cervus
      elaphus) was carried out. In the winter period the red blood cell (RBC) count was
      9.0 x 10(12)/L in adult fallow-does, and 6.1 x 10(12)/L in fawns. The haemoglobin
      (Hb) level and mean corpuscular volume (MCV) were also significantly (P < 0.05)
      lower in fawns than in adult fallow deer. In blood samples taken from red deer in
      different physiological and nutritional periods, the stags showed the lowest mean
      RBC count in January (4.7 x 10(12/L) and the hinds during lactation (6.3 x
      10(12)/L). The mean RBC count of samples taken from a group of red deer fawns at
      five different times between 1 week and 1 year of age varied between 5.8 and 7.0
      x 10(12)/L. In red deer herds the RBC count showed minor variations and the Hb
      concentration was almost constant in the different periods. The coefficient of
      correlation between RBC and Hb was 0.66 and 0.58 in fallow deer and red deer,
      respectively. Studying the blastogenic transformation of lymphocytes by
      immunological tests, a higher rate of response to non-specific mitogens
      (Phaseolus vulgaris, PHA; concanavalin A, Con A) was found in farmed deer (> 30%)
      than in deer captured in the wild and kept under farm conditions for 10 or 13
      months (< 20%).

PMID- 9270132
TI  - Brain-mediated protective interactions of histaminergic H2 and dopaminergic
      systems in rats.
AB  - Pretreatment with dopamine agonists (bromocriptine 2.5, L-dopa 2.5, apomorphine
      0.05 mg/kg i.p.) and a histamine H2 receptor antagonist (cimetidine 50.0 mg/kg
      i.p.) was found to greatly reduce the haemorrhagic gastric lesions induced by 15
      min pylorus ligation in rats. On the other hand, pretreatment with dopamine
      antagonists (haloperidol 5.0, sulpiride 1.0, domperidone 5.0 mg/kg i.p.)
      significantly aggravated these lesions. Cimetidine markedly diminished the
      ulcerogenic effect of haloperidol but not that of domperidone, suggesting a brain
      mediated site for the protective interaction of cimetidine and dopamine systems.

PMID- 9270133
TI  - The effect of beta-carotene and vitamins A, D3 and E on some reproductive
      parameters in cows.
AB  - Five groups of winter-housed cows (n = 10 per group) that calved in the winter
      were used to assess the effect of beta-carotene supplementation on postpartum
      reproductive performance. Near parturition and immediately after calving the beta
      carotene concentrations of the blood plasma were decreased and no differences
      could be found between the control and the supplemented groups. The results
      obtained at postpartum day 60 suggest that supplementation of the daily winter
      ration with 300 mg of synthetic beta-carotene with or without vitamins A, D3 and
      E exerts the most favourable effect on reproduction, as judged not only from B
      carotene and vitamin A contents of the blood plasma, colostrum and milk but also
      from the improved fertility indices. The number of inseminations per cow was
      reduced and the conception rate was significantly higher in cows supplied
      additionally with 300 mg of synthetic beta-carotene with or without vitamins A,
      D3 and E. It can be concluded that beta-carotene is an important factor in bovine
      reproduction and that its specific role cannot be taken over by vitamin A.

PMID- 9270134
TI  - Preliminary comparative studies on complement fixation, dot enzyme immunoassay,
      and western blotting for the detection of antibodies to Mycoplasma mycoides
      subspecies mycoides SC in Nigerian camel (Camelus dromedarius).
AB  - The serological prevalence of antibodies to Mycoplasma mycoides subsp. mycoides
      SC, the aetiological agent of contagious bovine pleuropneumonia (CBPP), was
      investigated in Nigerian camels. Fifty-eight serum samples were collected from
      slaughtered camels and examined by complement fixation (CFT), dot enzyme
      immunoassay and Western blots. Fourteen of the slaughtered camels examined had
      pneumonic lesions. All sera examined were negative by CFT but 7 (12.1%) and 4
      (6.8%) were positive by dot enzyme immunoassay and Western blots, respectively.
      The serological evidence of M. mycoides subsp. mycoides SC in camels and its
      likely implication in the epidemiology of CBPP are discussed.

PMID- 9270135
TI  - Purification and characterisation of the hexokinase of Plasmodium berghei, a
      murine malaria parasite.
AB  - Hexokinase (EC 2.7.1.1) activity in cell-free Plasmodium berghei was 35 and 5
      times higher as compared to normal and P. berghei-infected mouse erythrocytes,
      respectively. Maximal enzyme activity was present in the cytosolic fraction of
      the isolated parasite. Manifold purification of parasite hexokinase was achieved
      with Sephadex G-200. Sodium dodecyl sulphate polyacrylamide gel electrophoresis
      (SDS-PAGE) revealed parasite enzyme subunit in the molecular weight range of 47
      kDa with ATP (adenosine triphosphate) Km of 2 mM. Two out of three mice immunised
      with the hexokinase fraction were protected upon challenge with live parasites.

PMID- 9270136
TI  - Quantitative two-dimensional echocardiography in the horse: a review.
AB  - Quantitative two-dimensional echocardiography (2DE) was introduced into equine
      cardiology in the early 1990s. At first, linear and area dimensions and left
      ventricular volume were validated by the comparison of parameters determined
      during in vitro 2DE and autopsy measurements. Based on these studies, tomographic
      planes and intracardiac reference points for in vivo measurements were
      established and 2DE values have been determined for healthy adult horses by
      various authors. These data were similar to each other and proved to be
      comparable with M-mode echocardiography measurements. However, differences in the
      measured parameters are due to breed and body weight variations of the examined
      populations, as well as to technical differences between M-mode and 2DE
      measurement methods. Currently, little information is available on 2DE values in
      equine cardiac diseases. In one report, 23 horses with aortic insufficiency had
      significant increases in the mean values of left ventricular chamber size, aortic
      root diameter and shortening fraction, and left ventricular thickness was also
      increased. These values were measured by M-mode echocardiography, but diastolic
      left ventricular enlargement was also measured and illustrated by the use of 2DE.
      In another study, 38 horses with mitral insufficiency had increased diastolic
      values of left ventricular and atrial cross-sectional internal diameter.

PMID- 9270137
TI  - Hepatic ultrasonographic findings in experimental carbon tetrachloride
      intoxication of the dog.
AB  - An experimental study was undertaken in dogs with carbon tetrachloride (CCl4)
      intoxication to describe and follow the changes in the ultrasound appearance of
      the liver. Characteristic ultrasound features (enlarged liver, increased
      echogenicity with fine, tightly-packed echoes, and loss of echogenicity of the
      portal vein walls) were seen from day 2 of the experiment, culminating between
      days 2 and 7. Subsequently the liver gradually and almost completely regained its
      normal ultrasound appearance. Ultrasonographic findings corresponded to the
      severity of the clinicopathological parameters, and changed parallel with the
      results of liver biopsies. Histology of the biopsy samples revealed acute
      centrolobular lipid accumulation with necrobiosis and necrosis in the hepatocytes
      in the first stage of the disease. In the second stage, a secondary reparatory
      inflammatory process and reparation in the interstitial tissue were seen. In some
      dogs, ill-defined hyperechoic foci were observed within the liver during the
      regenerative phase. Hepatic ultrasonography seems to be a reliable and relatively
      sensitive method for monitoring liver dystrophy with necrobiosis and lipid
      accumulation and to follow the course of steatosis in clinical cases. Ultrasound
      guided biopsy can further improve the diagnostic accuracy of ultrasonography in
      liver dystrophy.

PMID- 9270138
TI  - Comparison of fullfat soybean, sunflower seed and protected fat as fat
      supplements for their effect on the performance of growing-finishing bulls and
      carcass fatty acid composition.
AB  - One hundred and twelve Holstein bulls (179-203 kg) were allotted to four dietary
      treatment groups (I: control; II: fullfat soybean diet; III: sunflower seed diet,
      and IV: protected fat diet) and used in a 120-day comparative feedlot trial to
      evaluate the effect of toasted fullfat soybean, whole sunflower seed and
      protected fat (calcium soap) on their weight gain, feed conversion and carcass
      fatty acid composition. The diets consisted of 45-46% concentrate and 55-54% corn
      silage. Digestibility, nutritive value as well as degradability were also
      determined. The apparent digestibility of dry matter, organic matter, N-free
      extract and crude protein as well as nutritive value were almost similar for the
      four diets. However, crude fibre, acid detergent fibre (ADF) and neutral
      detergent fibre (NDF) digestibilities decreased with increasing fat level but the
      differences were not significant. The inclusion of fullfat soybean or whole
      sunflower seed significantly (P < 0.05) increased the digestion of fat. Ruminal
      degradability of protein and dry matter were significantly (P < 0.01) lower for
      toasted fullfat soybean mixture compared to whole sunflower mixture. The
      inclusion of toasted fullfat soybean, whole sunflower seed and calcium soap in
      the diets was not effective in improving the bulls' weight gain or feed
      conversion in this trial. As both toasted fullfat soybean and whole sunflower
      seed increased the proportions of C18:1, C18:2 and C18:3 in adipose fat tissue
      and decreased the proportion of C16:0, they consequently significantly (P < 0.01)
      increased the ratio of unsaturated fatty acids. Whole sunflower seed was more
      effective than fullfat soybean. However, inclusion of the calcium soap had no
      effect on the fatty acid profiles in the present study.

PMID- 9270139
TI  - An unusual location for Ergasilus sieboldi Nordmann (Copepoda, Ergasilidae) on
      the operculum and base of pectoral fins of the pikeperch (Stizostedion lucioperca
      L.).
AB  - Ergasilus sieboldi infestation of the pikeperch (Stizostedion lucioperca) is
      extremely common in Lake Balaton. In the summer and autumn, these parasitic
      copepods have high prevalence and intensity on pikeperch of more than 20 cm body
      length. Typically, Ergasilus establish themselves in the folds on the external
      surface of the operculum and on the base of the pectoral fins, and only a small
      proportion cling to the gill filaments. Infestation is rare and of low intensity
      in pikeperch of less than 20 cm body length. The Volga pikeperch (Stizostedion
      volgense) has low-intensity infestation irrespective of age. The lesions caused
      by copepods present on the operculum are restricted to the epithelium even if
      infestation is intensive.

PMID- 9270140
TI  - Induction of acrosome reaction in dog sperm by calcium ionophore.
AB  - The sensitivity of the plasma membrane to calcium ionophore (A23187) challenge
      was studied in dog sperm using fluorescein lectin staining for the assessment of
      acrosomal status and viability. Second fraction ejaculates from 5 dogs were
      washed, resuspended in Ca(2+)-free (EDTA-treated), 50, 100, 500, 1000 and 2000
      microM/l Ca(2+)-containing Sp-TALP medium and induced with 50, 250, 500, 1000,
      2500 and 5000 nM/l calcium ionophore. Samples were collected from each aliquot
      after 30 and 60 min of induction to assess the percentage of acrosome reacted
      sperm cells (AR rate), viability and motility by fluorescein isothiocyanate
      conjugated peanut agglutinin (FITC-PNA) and ethidium-homodimer combined staining.
      On each slide, 200 sperm cells were assessed under epifluorescence microscope (x
      1250) in a blind manner. The response to ionophore challenge (AR rate, viability,
      motility) varied with Ca2+ and ionophore concentration in the suspension. A
      significantly higher AR rate was detected in samples containing 100, 500, 1000
      and 2000 microM/L Ca2+ (> 40%) than in that containing 50 microM/L. Acrosome
      reaction could not be successfully induced in the EDTA-treated sample and in any
      of the aliquots in which 50, 250 and 500 nM/L ionophore concentrations were used
      for induction. Motility decreased drastically in all of the treated samples and
      stopped in that sample where as significant AR rate could be detected. Viability
      remained high (> 75%) during the incubation and did not differ significantly in
      the treated and the control groups.

PMID- 9270141
TI  - Ovum pick up in swine: the influence of aspiration vacuum pressure on oocyte
      recovery from preovulatory follicles.
AB  - Endoscopical ovum pick up (OPU) in swine is a minimal invasive and reliable
      technique to aspirate oocytes from preovulatory follicles for studying
      intrafollicular development and oocyte maturation as well as for IVM/IVF
      programs. The aim of the present study was to determine the effect of different
      aspiration vacuum pressures on oocyte recovery and on the morphology of cumulus
      oocyte complexes (COCs). Oestrus of crossbred Landrace gilts (n = 33) was
      synchronized by feeding altrenogest and follicular growth was stimulated with
      1,000 IU PMSG 24 h after the last altrenogest application. On day 4 after PMSG
      application preovulatory healthy follicles of > 5 mm diameter were aspirated
      laparoscopically. Aspiration was carried out using a two-way cannula and an
      electronic aspiration pump. Five different vacuum pressures were used: 10, 17,
      32, 47 and 66 ml water/min, corresponding to 30, 60, 125, 250 and 375 mm Hg,
      respectively. Fluids from different follicles were pooled per ovary and the
      morphology of cumulus oocyte complexes (COCs) was determined microscopically
      immediately after aspiration. COCs were classified into oocytes with intact
      cumulus (i.e. compact or slightly expanded COC), oocytes with corona radiata and
      denuded oocytes. A total of 695 follicles were aspirated and 501 COCs recovered.
      Increasing the aspiration pressure stepwise from 10 ml water/min up to 66 ml
      water/min resulted in a decrease in oocyte recovery rate. A significant higher (P
      < 0.05) rate of oocyte recovery (77.4% v.s. 59.8%) was achieved using a vacuum
      pressure of 17 ml water/min compared to 66 ml water/min, respectively. There was
      a tendency to reduce the portion of COCs with intact cumulus from 82 to 88% to
      77% if the vacuum pressure increased to more than 47 ml water/min. A higher
      aspiration pressure provoked an increase (P < 0.05) in the number of denuded
      oocytes: 0 to 3% at 10 to 32 ml water/min, respectively, compared to 10% at 47 ml
      water/min to 17% at 66 ml water/min. These results demonstrate that variation in
      aspiration pressure affects oocyte recovery rate and COC quality. Aspiration
      vacuum pressure of 17 to 32 ml water/min was found to be optimal in swine both
      for oocyte recovery and COC quality.

PMID- 9270142
TI  - Weight-length relationships and reproduction of bream (Abramis brama L.) in
      Keszthely Bay of Lake Balaton.
AB  - The weight-length relationships of bream (Abramis brama L. 1758, family
      Cyprinidae) were studied in Lake Balaton, Hungary, Fish were randomly collected
      with a gill net from Keszthely bay between March and November 1995. The condition
      of bream was investigated monthly, using morphometric parameters of the body,
      fecundity estimations, and gonadosomatic indices (GSI). The weight-length
      relationships show that the body weight of bream increased at an approximately
      3.4 times higher rate than its length (b = 3.41). The GSI of females were always
      higher than those of the males. The GSI values of females reached their maximum
      (14.76-22.22) from March to May. Egg diameter is positively correlated with the
      spawning months, as demonstrated by the relationship found between egg diameter
      and GSI (r = 0.94; P < 0.001) Fecundity estimates exhibited a linear relationship
      to length and weight.

PMID- 9270143
TI  - Reduction of stress-induced changes in meat quality with thermolysed brewer's
      yeast of high nucleotide content in pigs.
AB  - The effect exerted by a biogenic performance enhancer of high nucleotide content
      on meat quality in 20 Norwegian Landrace pigs (90 to 95 kg) was examined. The
      diet of the treated group was supplemented with the performance enhancer for the
      last 30 days of fattening. The stress effect was transport to the slaughterhouse
      and slaughter itself. Plasma creatine kinase (CK), lactate dehydrogenase (LDH),
      and aspartate aminotransferase (AST) activities, glucose and cortisol
      concentrations, and muscle pH were determined. Serious stress damage was found in
      the cardiac and skeletal muscle, as indicated by the high CK (980 U/L), LDH (>
      1600 U/L) and AST (67 U/L) activities in the untreated group; values were
      significantly lower in the experimental pigs (458, 468 and 17 U/L, respectively).
      There were no significant differences in glucose and cortisol concentrations
      between the two groups. In the control group the pH values were significantly
      lower and more muscle samples showed PSE character than in the treated group (75
      and 30%, respectively).

PMID- 9270144
TI  - Principles of renal transplantation in the dog: A review.
AB  - The practically relevant body of knowledge available on renal transplantation in
      the dog is reviewed. A review of the history of renal transplantation is followed
      by a detailed description of the immunological fundamentals of transplantation,
      with especial regard to the structures directing rejection, the significance of D
      LA-typing and the MLR test serving for their determination, and the possible
      methods of nonspecific and specific immunosuppression. The most important
      criteria of recipient and donor selection are presented, together with the main
      aspects and medicinal protocol of prednisolone-azathioprine and prednisolone
      cyclosporin A immunosuppression within the framework of preparation for the
      surgical intervention. Among the surgical aspects of renal transplantation, first
      the recommended anaesthetic techniques are outlined, then the three stages of the
      surgical procedure, i.e. donor nephrectomy, renal perfusion and renal grafting,
      are described in detail. The last chapter of the article presents the physical,
      laboratory and instrumental diagnostic methods of rejection diagnosis, with
      special regard to their practical importance and different roles played in
      signalling the rejection.

PMID- 9270146
TI  - Malaria in the 1990s: plus ca change, plus ca meme chose.

PMID- 9270145
TI  - Public health implications of pneumococcal disease in indigenous Australians.

PMID- 9270147
TI  - On the tension between individual health rights and public health
      responsibilities.

PMID- 9270148
TI  - Reducing cervical cancer by two-thirds: a public health target within our reach.

PMID- 9270149
TI  - Consulting about priorities for the NHMRC National Breast Cancer Centre: how good
      is the nominal group technique.
AB  - The National Health and Medical Research Council National Breast Cancer Centre
      was established to improve outcomes for women by reviewing the literature,
      developing best practice guidelines and resources and developing a national
      monitoring system. Its broad terms of reference meant that it was important at
      the outset to identify priorities for action. The Centre used a national
      consultative process based on nominal groups to identify priorities. Thirteen
      consultative workshops were held with over 300 participants including women
      diagnosed with breast cancer, some of their families and health professionals.
      There was a high level of agreement between workshops in priorities identified,
      indicating that the nominal group process results in reliable data. A sub-sample
      of participants surveyed after the workshops reported being highly satisfied with
      their participation in the process. The findings indicate that the nominal group
      process can be useful in selecting priorities for action in health.

PMID- 9270150
TI  - Pap smears in general practice: a secondary analysis of the Australian Morbidity
      and Treatment Survey 1990 to 1991.
AB  - We investigated the characteristics of Australian general practice that predict
      performance of Pap smears by secondary analysis of the Australian Morbidity and
      Treatment Survey 1990 to 1991. Chi-squared analysis identified potential
      associations between Pap smear rate and patient, doctor and practice variables.
      Significant associations were examined using logistic regression and generalised
      estimating equations. Participants were 495 general practitioners who collected
      information on 113,468 doctor-patient encounters, of which 43,211 encounters
      involved females aged 18 to 70 years. Pap smear encounter (2449) were identified
      and classified as patient-requested (62 per cent), diagnostic (5 per cent) or
      opportunistic (33 per cent). The large difference in the unadjusted Pap smear
      rates per 100 female encounters for female general practitioners (11.7) and male
      general practitioners (4.2) required separate analysis by sex of the general
      practitioner. For male general practitioners, a Pap smear was less likely: as
      patient age increased; for new patients; for general practitioners with less
      general practice experience; for general practitioners with no postgraduate
      qualifications; with metropolitan practice location; and if the practice had more
      than 25 per cent of patients with English as a second language. For female
      general practitioners, a Pap smear was less likely: for older known patients; as
      the age of the general practitioners increased; and for management of fewer
      problems per 100 encounters. A Pap smear was less likely to be opportunistic: as
      patient age increased; for general practitioners who were Australian graduates;
      and for general practitioners with no postgraduate qualifications. Consideration
      of patient, doctor, and general practice characteristics may facilitate the
      design of interventions to improve cervical cancer screening.

PMID- 9270151
TI  - Effect of ethnic media on cervical cancer screening rates.
AB  - The effect on cervical screening rates of paid publicity on ethnic radio was
      evaluated. The radio publicity occurred during three discrete periods between
      1992 and 1994. The numbers of women having Pap smears before and after the
      intervention were compared in postcode areas with high and low percentages of
      residents of non-English-speaking background. During the second and third
      publicity periods, when the media coverage was more intense, a larger increase in
      screening rates was evident in postcode areas with high percentages of women of
      non-English-speaking background. Across the three intervention periods, the media
      publicity appeared to generate an additional 6.7 per cent (95 per cent confidence
      interval 4.4 to 9.2 per cent) increase in screening in areas with a high
      proportion of women of non-English-speaking-background compared with changes in
      screening in areas with a low proportion of women of non-English-speaking
      background. Paid publicity on ethnic radio may be an effective strategy to
      increase cervical screening rates among women of non-English-speaking background.

PMID- 9270152
TI  - Routine antenatal screening: not a case of informed choice.
AB  - Traditional epidemiological criteria are inadequate for comprehensively
      evaluating screening activities to identify best practice. In 1995, a study of
      women in the postnatal period at a major metropolitan teaching hospital in
      Victoria was conducted to assess, through their perspectives, the role of other
      factors of significance for the evaluation of routine antenatal screening. In
      particular, the role of informed choice was examined. The study involved a survey
      of 376 women and 21 semistructured interviews. The study found that, with an 'opt
      out' or routine system of screening, high rates of use were achieved at the
      expense of informed choice for some participants. In addition, disturbing
      differences in information delivery and information perception were found between
      public and private patients. The need for new criteria to identify what
      constitutes best practice in the delivery of antenatal screening programs is
      discussed. These criteria should incorporate consideration of broader social and
      ethical implications for women receiving antenatal screening.

PMID- 9270153
TI  - The best medicine: women using community health centres.
AB  - In an environment of scarce resources and competition for the health dollar,
      there is considerable pressure to close facilities viewed as specialist or to
      amalgamate them into the mainstream. Women's health services are presently among
      services subject to cuts and amalgamation, often on the assumption that they
      duplicate services available from private general practitioners. Another
      widespread belief is that women's health centres attract a small, elite clientele
      of 'worried well' feminist extremists. This study examined such assumptions,
      using questionnaire data collected from 388 women attending women's health
      centres (62 per cent) and mixed-sex community health centres (38 per cent).
      Findings showed that these clients of all community health facilities were
      disadvantaged compared with the population overall. When clients of women's
      health centres and community health centres were compared, the client profiles
      were either much alike or women's health centre clients were even more
      disadvantaged, challenging the stereotype of these centres being used only by a
      privileged elite. Instead, it appears that the centres offer a distinctive array
      of services to a socioeconomically vulnerable clientele, not a substitute for
      care available elsewhere.

PMID- 9270154
TI  - Pneumococcal vaccination: an important strategy to prevent pneumonia in
      Aboriginal and Torres Strait Island adults.
AB  - The objective of the study was to examine the appropriateness of the National
      Health and Medical Research Council (NHMRC) recommendations concerning
      pneumococcal vaccination for Aboriginal and Torres Strait Island adults.
      Laboratory surveillance of invasive pneumococcal disease identified 95 cases
      acquired by adults 15 years of age and over in Far North Queensland from 1992 to
      1995. The most common diagnosis was pneumonia (77 per cent). Sixty-one cases (64
      per cent) occurred in Aboriginal and Torres Strait Island adults, who acquired
      the disease at a younger age (mean 40 years) than did other adults (mean 50
      years). Most (93 per cent) of the Aboriginal and Torres Strait Island adults had
      at least one of the pre-existing medical conditions in the NHMRC criteria for
      pneumococcal vaccination. The most common was 'alcohol abuse' (62 per cent).
      Fifty-three (93 per cent) of the pneumococcal isolates from the Aboriginal and
      Torres Strait Island adults who had pre-existing conditions were serotyped. Fifty
      (94 per cent) belonged to types included in the currently available pneumococcal
      vaccine. We conclude that the NHMRC recommendations for pneumococcal vaccination
      are appropriate, considering the pattern of invasive pneumococcal disease that
      occurs in Aboriginal and Torres Strait Island adults in Far North Queensland.
      Because pneumococcal vaccination can reduce the pneumonia-associated morbidity
      and premature mortality experienced by Aboriginal and Torres Strait Island
      adults, the vaccine should be offered routinely to those considered to be at
      risk, particularly young men who have recently begun to consume hazardous amounts
      of alcohol, and recently diagnosed diabetics.

PMID- 9270155
TI  - Walking to school and traffic exposure in Australian children.
AB  - Daily patterns of pedestrian activity in young children have important health
      implications, primarily because of the risk of road traffic injury, but also
      because they may reflect the commencement of exercise habits with long-term
      consequences. A cross-sectional survey in two Australian cities, Melbourne and
      Perth, aimed to collect, by parent self-administered questionnaire, population
      based data on modes of travel, numbers of street crossings (both accompanied and
      unaccompanied by an adult), and sociodemographic factors for six- and nine-year
      old children. Results indicate that 35 per cent (95 per cent confidence interval
      (CI) 31 to 39 per cent) and 31 per cent (CI 28 to 34 per cent) walk to school in
      Melbourne and Perth respectively, while over 60 per cent are driven to school by
      car, with very small proportions riding bicycles or taking public transport. A
      higher level of walking was associated with lower levels of several indicators of
      socioeconomic status. Logistic regression analysis showed that the strongest
      predictor of walking activity was school type (government versus independent),
      and after adjusting for this, lesser car ownership, non-English-speaking
      background and lower occupational category were associated with walking to
      school, while a different set of predictors--age, sex and maternal education--was
      associated with the unaccompanied crossing of streets. There was little
      difference in overall walking levels between boys and girls, but boys were
      significantly more likely to cross streets unaccompanied (adjusted odds ratio
      1.41, CI 1.14 to 1.72), providing a partial explanation of documented sex
      differences in injury rates.

PMID- 9270156
TI  - Hepatitis B immunisation rates among infants in ethnic groups with high
      prevalences of hepatitis B surface antigen carriers.
AB  - To determine hepatitis B immunisation rates in infants from ethnic groups with
      hepatitis B surface antigen chronic carrier prevalence over 5 per cent, a
      questionnaire was sent to all Maternal and Child Health Centres in Victoria,
      requesting information on the hepatitis B and diphtheria-tetanus-pertussis (DTP)
      or combined diphtheria-tetanus (CDT) immunisation status for all infants born
      between 1 July 1992 and 30 June 1993 and at risk of hepatitis B infection because
      of maternal ethnicity. We received data on 3611 of 5744 infants (62.9 per cent)
      in targeted ethnic groups. Of these, 12.8 per cent had not received hepatitis B
      vaccine, and 81.6 per cent, 76.8 per cent and 64.0 per cent had received at least
      one, two and three doses respectively, while 84 per cent had received at least
      three doses of DTP vaccine and/or CDT vaccine. Coverage with DTP or CDT was
      higher than for hepatitis B vaccine (P < 0.001), and coverage was better in areas
      with a higher percentage of infants in high-prevalence ethnic groups (P < 0.001).
      Changes in the program in Victoria in terms of timing of the first dose of
      vaccine plus greater attention to follow-up may lead to improved hepatitis B
      immunisation rates among infants in targeted ethnic groups. Adoption of universal
      infant hepatitis B immunisation, by increasing familiarity with hepatitis B
      vaccine, is likely to be the best way to increase immunisation coverage for these
      infants.

PMID- 9270157
TI  - Eucalyptus oil poisoning among young children: mechanisms of access and the
      potential for prevention.
AB  - We studied unintentional paediatric eucalyptus oil poisoning to identify
      potential intervention strategies. The epidemiology of paediatric eucalyptus oil
      poisoning in Victoria was determined by analysis of four databases. The sequence
      of events preceding ingestion was examined by a telephone survey involving 109
      parents or guardians of children under five years involved in an actual or
      suspected ingestion of eucalyptus oil. Such children were identified
      prospectively from all callers during a nine-month period to the Victorian
      Poisons Information Centre and those presenting to the emergency departments of
      the participating hospitals of the Victorian Injury Surveillance System.
      Eucalyptus oil was a leading agent associated with hospitalisation for poisoning
      among Victorian children aged under five years. In the telephone survey, 90
      incidents were found to involve vaporiser solutions, 15 eucalyptus oil
      preparations, and the remainder other eucalyptus-oil-containing products of a
      medicinal nature. Regardless of the type of product, 74 per cent gained access
      via a home vaporiser unit, most frequently placed at ground level. Although
      amounts ingested are usually small, the reported range of toxic doses is wide,
      necessitating at least a medical assessment following ingestion. Potential
      countermeasures identified in a consultative workshop included: discontinuing the
      use of eucalyptus oil as a therapeutic agent; confirmation that vaporiser-well
      residues are nontoxic; removal of barriers to product reregistration following
      safety-related modifications; improved child-resistant closures; discouraging
      vaporiser use for respiratory infections among young children; and development
      and dissemination of protocols for treatment of suspected ingestion.

PMID- 9270158
TI  - Food insufficiency in Queensland.
AB  - To investigate the prevalence of food insufficiency and factors associated with
      it, two questions assessing household and individual food insufficiency were
      included in 13 regional health surveys conducted in Queensland in 1993. The
      surveys used computer-assisted telephone interviewing methodology. Of the 10,451
      people interviewed, 9.7 per cent and 6.4 per cent reported household and
      individual food insufficiency, respectively, and 11.3 per cent reported at least
      one type. Prevalence was significantly higher in women than men and in urban than
      rural residents, and decreased monotonically with increasing age from 16.6 per
      cent in 18- to 30-year-olds to 1.7 per cent in over-70-year-olds. Higher
      prevalence also was associated with lower income, unemployment, single or
      separated, divorced or widowed status versus married (or de facto), one-adult
      households, and shared accommodation. Lower prevalence was associated with more
      education in those aged 50 and under but not in those over 50 years. Using
      logistic regression to control simultaneously for important sociodemographic
      factors, we found that risk of food insufficiency was most highly associated with
      age and income (threefold risk), unemployment and shared accommodation (twofold
      risk) and one-adult households, and being single versus separated, widowed or
      divorced (one-and-a-half-fold risk). Some differences in risks existed between
      men and women and between rural and urban residents, although none excluded the
      role of chance. Association of the items with lower reported fruit, vegetable and
      meat intake, poorer health status, and greater underweight supports their
      validity.

PMID- 9270159
TI  - Health care costs of people referred to an aged care assessment team: the effect
      of cognitive impairment.
AB  - The aim of this study was to determine the effect cognitive impairment has on
      direct and indirect costs to elderly people, their carers and the community over
      one year, by following prospectively a cohort of elderly people referred to an
      aged care assessment team. The 78 subjects were drawn from a random sample of
      people referred to the NorthWest Hospital team, and validated tools were used to
      assess their cognitive state. Outcome measures included total costs of community
      services, residential care, hospital bed use, carer burden and psychological
      morbidity. A comparison of outcome measures was made between those with cognitive
      impairment and those without. Use of community services and hospital beds was
      high overall. Those with cognitive impairment were substantially greater users of
      residential care, accounting for the higher expenditure in this group.
      Psychological morbidity and burden remain high in carers of those with cognitive
      impairment despite a high rate of institutionalisation in this group. The total
      costs for those referred to aged care assessment teams with cognitive impairment
      are double those seen for those with normal cognition.

PMID- 9270160
TI  - The role of general practitioners and pharmacists in information exchange with
      family carers.
AB  - As a trial of the provision of community-service information to family carers,
      general practitioners and pharmacists from the Western region of Melbourne were
      supplied with tear-off pads listing suburb-specific community services, and were
      encouraged to discuss service needs with carers of people with disabilities and
      distribute the lists to carers accordingly. One hundred and nine general
      practitioners and 58 pharmacists participated in pretrial and post-trial
      interviews assessing their knowledge of community services and frequency of
      discussion with carers. Before the trial, general practitioners had significantly
      higher self-rated knowledge of community services and reportedly discussed these
      with carers more often than did pharmacists. After the five-month trial period,
      pharmacists showed a significant increase in self-rated knowledge and frequency
      of discussion. General practitioners' knowledge and discussion showed a
      nonsignificant increase. After the trial, the two did not differ in knowledge of
      services; however, general practitioners maintained a higher reported frequency
      of discussion about services with carers. General practitioners and pharmacists
      appear to be well placed to act as a service link for family carers. However,
      additional high-intensity strategies are needed to assist them in this role.

PMID- 9270161
TI  - Implementation of ethnic health policy in community mental health centres in
      Melbourne.
AB  - The implementation of ethnic health policy in community mental health centres was
      investigated by using structured interviews with coordinators and staff of 13
      centres in Melbourne. The major finding was that most policy recommendations were
      not implemented and that work on ethnic issues resulted from the initiatives of
      individual staff. The study demonstrates that the successful implementation of
      ethnic health policy requires higher priority from policy makers and government,
      greater attention to mechanisms to require or encourage implementation, and a
      strategy to ensure that resources (new or redirected) are allocated to the
      implementation process.

PMID- 9270162
TI  - Sun behaviour and perceptions of risk for melanoma among 21-year-old New
      Zealanders.
AB  - This study investigated perceived risk of melanoma, sunscreen use and frequency
      of sunburn in a large sample of young New Zealanders. A self-report questionnaire
      was administered to a sample of 909 21-year-olds to survey their perception of
      how sun behaviours affect their risk of getting melanoma, how often they get
      sunburn, how often they use sunscreen and what factors would get them to use
      sunscreen more often. Knowledge of melanoma was high, but myths concerning 'safe
      tanning' persisted. Many young adults believed that sunbathing regularly using a
      sunscreen and obtaining a good base tan from gradual sun exposure decreased their
      risk of getting melanoma. They were unsure about the use of artificial sun beds
      and if their use would increase or decrease their risk. Males and females
      differed significantly on many aspects of their sun behaviour. Most used
      sunscreen only 'sometimes' and its use was linked to knowledge of melanoma and
      perceptions of risk. The best way to modify the sun behaviour of young adults is
      to target both their knowledge of melanoma risk factors and their perceptions of
      risk.

PMID- 9270163
TI  - Accuracy of women's recall of opportunistic recruitment for cervical cancer
      screening in general practice.
AB  - Evaluation of strategies to improve opportunistic recruitment via general
      practice of women overdue for a cervical smear requires an accurate behavioural
      measure. As part of an experimental trial to evaluate the effect of a
      postgraduate workshop on preventive care, we conducted this methodological study
      to determine the accuracy of women's recall of an opportunistic discussion about
      cervical screening, by comparing it against audiotapes (n = 524). Taking the
      taped evidence of the trainee's verbal behaviour as the gold standard,
      sensitivity was 85 per cent (95 per cent confidence interval (CI) 73.1 to 92.0
      per cent) and specificity was 78 per cent (CI 73.9 to 81.6 per cent). Given the
      low rate of opportunistic recruitment by trainees in the main study, only one
      third of positive recollections by women of an opportunistic discussion about
      cervical screening were correct. Until other measures have been validated,
      women's recall may continue to be used to measure general practitioners'
      behaviour, but an appreciation of likely bias is recommended.

PMID- 9270164
TI  - Validity of self-reported hysterectomy and tubal sterilisation. The Survey of
      Women's Health Study Group.
AB  - Both hysterectomy and tubal sterilisation offer significant protection from
      ovarian cancer, and the risk of cardiovascular disease in women is lowered after
      hysterectomy. Since little is known about the accuracy of women's self-reports of
      these procedures, we assessed their reliability and validity using data obtained
      in a case-control study of ovarian cancer. There was 100 per cent repeatability
      for both positive and negative histories of hysterectomy and tubal sterilisation
      among a small sample of women on reinterview. Verification of surgery was sought
      against surgeons' or medical records, or if these were unavailable, from randomly
      selected current general practitioners for 51 cases and 155 controls reporting a
      hysterectomy and 73 cases and 137 controls reporting a tubal sterilisation.
      Validation rate for self-reported hysterectomy against medical reports (32 cases,
      96 controls) was 96 per cent (95 per cent confidence interval (CI) 91 to 99) and
      for tubal sterilisation (32 cases, 77 controls) it was 88 per cent (CI 81 to 93),
      which is likely to be an underestimate. Although findings are based on small
      numbers of women for whom medical reports could be ascertained, they are
      consistent with other findings that suggest women have good recall of past
      histories of hysterectomy and tubal sterilisation; this allows long-term effects
      of these procedures to be studied with reasonable accuracy from self-reports.

PMID- 9270166
TI  - Internal markets and Aboriginal health.

PMID- 9270165
TI  - Vehicle crash mortality in the Kimberley region, 1990 to 1994: the role of open
      load-space passengers in utility trucks.
AB  - Coroner's reports, police records and the state crash database provided
      information on 65 crash fatalities in the Kimberley region of Western Australia
      from 1990 to 1994. Passengers travelling in the open load space of utility trucks
      comprised 18 per cent of fatalities. Open-load-space passenger fatalities were
      associated with open highway or community access road travel. The fatality rate
      for the region was 41.5 per 100,000 population and the rate ratio for Aboriginal
      to non-Aboriginal fatalities was 2.5. Only 50 of the 65 identified deaths were
      included in official crash statistics. State crash statistics do not provide
      information on the position of passengers in road crashes.

PMID- 9270167
TI  - Respiratory signs in Aboriginal communities.

PMID- 9270168
TI  - Need for evidence about fluoridation.

PMID- 9270169
TI  - Evidence on fluoridation.

PMID- 9270170
TI  - Evidence on fluoridation.

PMID- 9270171
TI  - Whither private health insurance?

PMID- 9270172
TI  - A consumer response to the immunisation debate.

PMID- 9270173
TI  - Increased frequencies of sister chromatid exchanges and micronuclei in "in vitro"
      lymphocyte cultures treated with the fungicides thiram and ziram.
AB  - The two fungicides analysed in this paper, Thiram (TH) and Ziram (ZI) are among
      the most common residues found in fruit and vegetables sold in Italy. These
      compounds were tested in "in vitro" lymphocyte cultures, from 16 individuals, at
      different concentrations (Thiram 5 x 10(-8) M; 5 x 10(-7) M; 5 x 10(-6) M and
      Ziram 1 x 10(-7) M; 1 x 10(-6) M; 1 x 10(-5) M) in order to ascertain if they are
      able to modify sister chromatid exchange and/or micronuclei frequencies. Both
      fungicides produced a significant increase in SCE and Micronuclei frequencies.
      The two highest doses of TH and ZI were found to be cytotoxic for most of the
      individuals and were not included in the statistical analysis. With regard to the
      Proliferation Rate Index (i.e. the number of first, second, third or more
      mitoses), no difference was found between controls and treated cultures.

PMID- 9270174
TI  - PCR analysis of the STR HUMF13A01 in a population sample of central Italy.
AB  - A population genetic study was carried out on an Italian sample of Central Italy
      (n = 159) using the short tandem repeat (STR) system HUMF13A01. After vertical
      electrophoresis in denaturing polyacrylamide gel, 11 alleles were found. No
      deviation from the Hardy-Weinberg equilibrium were observed. The power of
      discrimination (PD) was 0.91 and the chance of exclusion was 0.59. The allelic
      comparison with previous Italian population studies showed no significant
      difference.

PMID- 9270175
TI  - Blackcurrant seed oil, zinc, and fetal alcohol syndrome.
AB  - The effects of dietary supplementation by blackcurrant seed oil (BSO) and zinc
      sulphate on PGI2 gastric release and on serum zinc levels were investigated in 50
      pregnant Sprague-Dawley rats which received watery alcohol solutions from 5% to
      30% (v/v) as well as in their newborns. Blood zinc was assayed by atomic
      absorption spectroscopy; PGI2 was evaluated by platelet aggregation PGI2
      dependent test. Dietary supplementation by BSO increased gastric release of PGI2
      both in the mothers and their newborns; blood zinc levels were significantly (p <
      0.01) lower in both vs control. The content of PGI2 in the stomachs was
      significantly (p < 0.01) higher in the mothers treated by zinc sulphate vs their
      new-borns. Protection of gastric mucosa of the new-born rats from alcohol fetal
      exposure might depend on polyunsaturated fatty acids (PUFA) dietary
      supplementation, because of the capability of PUFA to cross placenta; the
      efficacy in the protection might be monitored by platelet aggregation PGI2
      dependent test.

PMID- 9270177
TI  - An electron microscopical investigation of small round viruses in non-bacterial
      gastroenteritis.
AB  - Small round viruses implied in non-bacterial gastroenteritis were observed by
      electron microscope in stool specimens collected from 1993 to 1996. The specimens
      relative to 1981 were re-examined. The identified viruses are astroviruses (n =
      6), caliciviruses (n = 7), Norwalk-like viruses (n = 34) and Parvoviruses (n =
      6). Immunoelectron microscopy (IEM) and solid-phase immunoelectron microscopy
      (SPIEM) were used in order to verify serological differences existing among
      Norwalk-like viruses from different outbreaks. The results obtained suggest a
      possible circulation, in Liguria, of two serotypes of antigenically different
      viruses in the period considered.

PMID- 9270176
TI  - Opiate-related death: morphometric study of neurons from the dorsal motor nucleus
      of the vagus nerve.
AB  - The aim of this work is to verify the presence of objectively observable
      morphological alterations caused by the direct action of opiates on brain
      structures controlling respiration in cases of drug-related deaths. A computer
      assisted morphometric study was carried out on the Dorsal Motor Nucleus of the
      Vagus Nerve (DMNV) in seven subjects (four of whom died of drug overdose, and 3
      controls). Serial sections 10-15 microns thick were stained according to Nissl.
      The sections were then examined under the optical microscope and 200 fields per
      subject were digitalized. The resulting images, regarding at least 700 neurons
      per subject were segmented using a semi-automatic procedure and analysed by the
      Optilab software. The data obtained were subjected to cluster analysis to
      identify the neuron classes in the DMNV. Each subject was characterized with a
      vector of percentages indicating the fraction of neurons falling in each of these
      classes. Discriminant analysis was then applied to verify to what extent the
      variables discriminated between the two populations. Results indicated that: the
      statistical methods adopted have a good power of discrimination; in subjects who
      died of opiate overdose, the neurons are distributed to a greater extent in
      classes composed of smaller neurons than in controls.

PMID- 9270178
TI  - Impact of therapy on left ventricular remodeling after myocardial infarction: an
      echocardiographic perspective.

PMID- 9270179
TI  - Oxidative stress, endothelial function and coronary atherosclerosis.

PMID- 9270180
TI  - [Mechanisms facilitating oxygen delivery during exercise in patients with chronic
      heart failure].
AB  - The aim of the study was to estimate the relative importance of the Bohr effect
      and redistribution of blood from the non-exercising tissues on the arterial
      venous oxygen content differences across the exercising extremities and the
      central circulation in patients with chronic heart failure; the relationship
      among femoral vein, systemic and pulmonary artery oxygen partial pressure and
      hemoglobin saturation was determined. It has been reported that the maximal
      reduction in femoral vein pO2 precedes peak oxygen consumption and lactic
      acidosis threshold in patients with chronic heart failure and normal subjects
      during exercise. The increase in oxygen consumption at work rates above lactic
      acidosis threshold, therefore, must be accounted for by increase in blood flow in
      the exercising muscles and right-ward shift on the oxyhemoglobin dissociation
      curve. Since the total cardiac output increase is blunted in patients with
      chronic heart failure, diversion of blood flow from non-exercising to exercising
      tissues may account for some of the increase in muscle blood flow. Ten patients
      with chronic heart failure performed a progressively increasing leg cycle
      ergometer exercise test up to maximal effort while measuring ventilation and gas
      concentration for computation of oxygen uptake and carbon dioxide production,
      breath-by-breath. Blood samples were obtained, simultaneously, from systemic and
      pulmonary arteries and femoral vein at rest and every minute during exercise to
      peak oxygen consumption. At comparable levels of exercise, femoral vein pO2,
      hemoglobin saturation and oxygen content were lower than in the pulmonary artery.
      PCO2 and lactate concentration increased steeply in femoral vein and pulmonary
      artery blood above lactic acidosis threshold (due to lactic acid build-up and
      buffering), but more steeply in femoral vein blood. These increases allowed
      femoral vein oxyhemoglobin to dissociate without a further decrease in femoral
      vein pO2 (Bohr effect). The lowest femoral vein pO2 (16.6 +/- 3.9 mmHg) was
      measured at 66 +/- 22% of peak VO2 and before the lowest oxyhemoglobin saturation
      was reached. Artero-venous oxygen content difference was higher in the femoral
      vein than in the pulmonary artery; this difference became progressively smaller
      as oxygen consumption increased. "Ideal" oxygen consumption for a given cardiac
      output (oxygen consumption expected if all body tissues had maximized oxygen
      extraction) was always higher than the measured oxygen consumption; however the
      difference between the two was lost at peak exercise. This difference positively
      correlated with peak oxygen consumption and cardiac output increments at
      submaximal but not at maximal exercise. In conclusion, femoral vein pO2 reached
      its lowest value at a level of exercise at or below the lactic acidosis
      threshold. Further extraction of oxygen above the lactic acidosis threshold was
      accounted for by a right shift of the oxyhemoglobin dissociation curve. The
      positive correlation between increments of cardiac output vs "ideal" and measured
      oxygen consumption suggests a redistribution of blood flow from non-exercising to
      exercising regions of the body. Furthermore the positive correlation between
      exercise capacity and the difference between "ideal" and measured oxygen
      consumption suggests that patients with the poorer function have the greater
      capability to optimize blood flow redistribution during exercise.

PMID- 9270182
TI  - Communicable diseases surveillance.

PMID- 9270181
TI  - Annual report of the Australian Meningococcal Surveillance Programme 1996.
AB  - The Australian Meningococcal Surveillance Programme has undertaken meningococcal
      isolate surveillance by means of a collaborative laboratory-based initiative
      since 1994. Serogroup data have been enhanced by the addition of serotype and
      serosubtype information in 1996. Ninety-two per cent of the 297 invasive isolates
      of Neisseria meningitidis examined in 1996 were serogroup B or C. Serogroup B
      strains predominated in all States and Territories and were isolated from
      sporadic cases of meningococcal disease. Serogroup C isolates were prominent in
      New South Wales, Queensland and the Northern Territory, and were also associated
      with mainly sporadic cases of meningococcal disease. A number of case clusters
      also occurred in association with serogroup C strains. Although most sporadic
      cases of meningococcal disease showed a diversity of phenotypes, clusters of
      cases were noted with the phenotypes C:2a:P1.5 and C:2a:P1.2,5. The number of
      isolates with the phenotype B:4:P1.4 also increased in New South Wales and
      Queensland. The proportion of isolates showing decreased susceptibility to the
      penicillin group of antibiotics (minimal inhibitory concentration, MIC, 0.06 to
      0.5 mg/L) increased to 74% in 1996. Three isolates showed reduced susceptibility
      to rifampicin.

PMID- 9270183
TI  - A regional weaning center for patients requiring mechanical ventilation: an 18
      month experience.
AB  - This report reviews the outcomes of patients on mechanical ventilation admitted
      to a new regional weaning center. We reviewed the records of 47 patients admitted
      to the weaning center over an 18-month period. All patients had a tracheostomy,
      were ventilator dependent, and considered difficult to wean by their referring
      physician. The mean days of ventilator dependence prior to transfer to our
      facility was 86 days, with a range of 21 to 332 days. Patients were admitted to a
      12-bed weaning unit at our chronic disease and rehabilitation hospital and
      assessed by a multi-disciplinary team of physicians, nurses, and therapists.
      Thirty patients were successfully weaned from prolonged mechanical ventilation
      and subsequently discharged from our unit. These data indicate that the majority
      of difficult to wean patients admitted to our regional weaning center were
      successfully liberated from prolonged mechanical ventilation.

PMID- 9270184
TI  - Counseling for physical activity: what primary-care physicians should know.
AB  - In Connecticut, 22.1% of the adult population report no physical activity other
      than activities of daily living. Primary care physicians can play a vital role in
      the flight against a sedentary lifestyle. As outlined in Healthy People 2000 and
      the Surgeon General's Report on Physical Activity and Health, the primary-care
      physician's role in the assessment and advising of physical activity is critical.
      The primary-care physicians that responded to the Connecticut survey appear to be
      doing an excellent job in delivering this important message. Recommendations made
      by the primary-care physician can be a great source of motivation for the
      patient. The primary-care physician's initial goal should be to get the patient
      active on a daily basis and than progress to more health-based fitness goals. The
      patient needs to receive instruction on goal setting, safe exercise tips, and
      adherence strategies. The primary-care physician's low-cost intervention of
      advising physical activity can help prevent medical problems in the future. The
      most current recommendation on physical activity states that, "All U.S. adults
      should accumulate 30 minutes or more of continuous or intermittent amounts of
      moderate-intensity physical activity on most, preferably all, days of the week."
      This latest recommendation offers primary-care physicians a broader range of
      activities to suggest to their patients. An overwhelming number of research
      studies indicate that physical activity is a powerful weapon in combating a host
      of lifestyle-related health problems.

PMID- 9270185
TI  - Laryngeal chondrosarcoma: a case report with radiological-pathological
      correlation.

PMID- 9270186
TI  - Armorers and barber surgeons: a remarkable legacy. Graduation address for the
      Newington Orthotics and Prosthetics School 20 May 1996.

PMID- 9270187
TI  - Managed-care organizations' teaching role: its importance in medical education.
AB  - One of the central issues driving integrated system development is educating
      physicians in managed care. Managed-care organizations need to become more
      involved in medical education, especially its clinical teaching functions. This
      affects largely the ambulatory aspects of care and generalist physician training.
      Academic medical centers and managed-care organizations can achieve this mission
      through collaboration.

PMID- 9270188
TI  - Doctor, I need my license.

PMID- 9270189
TI  - The Supreme Court's decision: the debate will continue.

PMID- 9270190
TI  - In response to Dr. Deren's president's page "Immune from criticism".

PMID- 9270191
TI  - Oath of Hippocrates vs the Wall Street Journal?

PMID- 9270192
TI  - Concerning Dr. Waters' and Dr. Kiernan's "The abuse of cardiovascular
      procedures".

PMID- 9270202
TI  - Delayed traumatic hernia of the diaphragm presenting with hypertensive
      pneumothorax. Case report and review of the literature.
AB  - The diagnosis of traumatic hernia of the diaphragm can be obtained at the time of
      injury or months-years after the trauma. The Authors report a case of traumatic
      hernia of the diaphragm, diagnosed 3 years after a blunt thoracic trauma in a 47
      year-old man. The patient was admitted to the hospital for a pneumothorax caused
      by perforation of the herniated colon. He underwent colonic resection and
      reduction of the herniated viscera but unfortunately he died of septic shock on
      the 40th postoperative day. Pneumothorax is a very rare complication of traumatic
      diaphragmatic hernia and few cases are reported in literature. The diagnosis in
      the delayed phase is not easy since the correlation with the trauma is not always
      clear.

PMID- 9270203
TI  - Children's environmental health.

PMID- 9270204
TI  - Disappearing and emerging infectious diseases.

PMID- 9270206
TI  - The limits of childhood: adolescent health care in pediatric practice.

PMID- 9270207
TI  - Three decades of evolution in diabetes care for children.

PMID- 9270205
TI  - Immunizations.

PMID- 9270208
TI  - Pediatric imaging in the 1990s.

PMID- 9270209
TI  - Drugs and the college athlete: an analysis of the attitudes of student athletes
      at risk.
AB  - Theories related to planned behavior and reasoned action have included an
      individual's attitude as an important factor in the formation of behavioral
      intentions and behaviors. Research on this topic suggests that salient beliefs
      affect intentions and subsequent behaviors, either through attitudes or
      subjective norms, or the degree of (perceived) control that an individual feels
      he/she has over the behavior. This study was designed to examine the relative
      importance of selected attitude variables in describing a profile of athletes who
      were at risk for using anabolic steroids, human grown hormone, amphetamines,
      cocaine, and marijuana. Responses from 563 student athletes at two Division One
      NCAA universities were used in the study. The results of this study suggest that
      subjective norms, based on the influence of drug testing, peer influence, and a
      fear of detection are significant factors that influence the decisions of student
      athletes related to using banned substances. In this article characteristics of
      at-risk athletes are presented with recommendations for drug education programs
      for student athletes.

PMID- 9270210
TI  - Examining athletes' attitudes toward using anabolic steroids and their knowledge
      of the possible effects.
AB  - One goal of contemporary sports leaders is to eradicate the use of banned drugs
      in competitive sport. A common approach to achieving this outcome is to provide
      athletes with adequate education about the effects of drug use. Ostensibly,
      educational programs about the deleterious effects of using anabolic steroids are
      thought to discourage their intake. Thus, the purpose of this study was to
      examine the relationships between the athletes' knowledge about the long-term
      effects of anabolic steroids and their attitudes toward this type of drug.
      Multiple regression analyses indicated relatively low R2's and correlations
      between the various components of subjects' knowledge and their attitude toward
      steroid ingestion. This suggests that educational programs for athletes about
      taking anabolic steroids may have limited value in terms of creating appropriate,
      responsible attitudes toward this illegal, unethical, and medically questionable
      practice.

PMID- 9270211
TI  - Psychosocial correlates of substance use: comparing high school students with
      incarcerated offenders in Hong Kong.
AB  - Drug use prevalence data were obtained from 969 adolescents, high school students
      and imprisoned offenders who reported use of cough medicine, organic solvents,
      cannabis, heroin, tranquilizers, and narcotics over the past six months.
      Incarcerated youths, in particular girls, had higher prevalence rates than
      students. Drug use frequencies were associated with psychosocial variables such
      as disinhibition, peer drug use, susceptibility to peer pressure, attitudes,
      encouragement by peers, and perceived availability of drugs. The psychosocial
      process of the initiation and maintenance of substance use was specified as a
      path model that considered 1) personality and social environment as distal
      precursors and 2) a drug-use predisposition and perceived availability as
      proximal precursors of three kinds of outcome variables: drug use, the intention
      to try illicit drugs if they were legal, and adverse outcomes of drug use. It was
      found that the same structural equation model fit the data of both samples of
      offenders and students, however, with very different weights assigned to the
      paths.

PMID- 9270212
TI  - Informational and symbolic content of over-the-counter drug advertising on
      television.
AB  - The informational and symbolic content of 150 over-the-counter drug commercials
      on television are empirically analyzed in this study. Results on the
      informational content suggest that over-the-counter drug ads tend to focus on the
      concern of what the drug will do for the consumer, rather than on the reasons why
      the drug should be ingested. Accordingly, advertising strategy is centered on
      consumer awareness of the product as the primary goal. Educational commitment,
      however, did not seem to be blended into the promotional efforts for over-the
      counter drugs. Findings on the symbolic content of over-the-counter drug ads
      reveal that drug images have been distorted. Performance of most drugs has been
      portrayed to be simple resolutions to relieve the symptom. Moreover, a casual
      attitude toward drug usage is encouraged in the commercials, while time lapse of
      drug effects is overlooked.

PMID- 9270214
TI  - Dentists' HIV-related ethicality: an empirical test.

PMID- 9270215
TI  - A brief guide to using a lawyer's mind in healthcare business situations.
AB  - A lawyer experienced in contract aspects of dental law explores the differences
      between the ways dentists and lawyers are trained to think about business
      problems and opportunities. Lawyers are trained to analyze situations to look for
      alternatives and apply the law to the facts of the case. It is the nature of the
      law not to have scientifically justified general approaches (what dentists might
      call parameters or best practice rules). For the lawyer, multiple sources of law,
      legislative, judicial and regulatory, coupled with the details of a case, provide
      the framework for decision-making. This can place a premium on finding a lawyer
      familiar with the field of law in question. Lawyers provide a valuable service in
      negotiating, mediating, and otherwise finding alternatives to litigation.
      Communication skills are essential because of the complexity of many legal
      situations and because the lawyer never decides the correct course of action for
      a client--the client must do this based on his or her goals and the alternatives
      presented.

PMID- 9270213
TI  - Parenting styles, adolescent substance use, and academic achievement.
AB  - This article investigates how children and their parents rate their parenting
      styles, and how this rating is associated with academic achievement, alcohol, and
      tobacco use. We surveyed students and their parents in two public school
      districts. A total of 386 matched parent-child pairs from eighth- and ninth-grade
      students were analyzed for parent and student classification of parents as
      authoritative, authoritarian, permissive, or mixed parenting styles. Agreement on
      parenting styles between parents and children was poor. Students perceived
      parents as less authoritative, less permissive and more authoritarian than
      parents considered themselves. High grades were associated with child and parent
      perception of higher authoritativeness, lower permissiveness, and lower
      authoritarianism. Child tobacco and alcohol use was associated with child
      perception of lower authoritativeness, and higher permissiveness while parent
      perception of parenting style was not associated with child substance use. This
      study provides further evidence that parenting styles and adolescents'
      perceptions of them are associated with child achievement and substance use.
      While we cannot determine whether child or parent perception of parenting style
      is more accurate, child perception is more strongly associated with grades and
      substance use than is parent perception. It is likely that parents would benefit
      from understanding how they are perceived by their children.

PMID- 9270216
TI  - Suits other than malpractice--loss of license.
AB  - Acts and negligence on the part of dentists which result in the revocation or
      suspension of the license to practice are discussed. The California Business and
      Professions Code and the California Rules and Regulations are used to present
      examples from the areas of inspection of books, records, and premises; conviction
      of a crime; and unprofessional conduct. The acts that provoke civil litigation
      and state and federal agency action, incompetence, gross and repeated negligence,
      unprofessional conduct, safety in the work place, sexual harassment, and fraud
      are also the acts that subject the licensee to discipline from the Board.
      Investigative and hearing procedures, penalties, appeal, and due process are also
      discussed.

PMID- 9270218
TI  - Malpractice--the dentist's perspective.
AB  - A lawyer with more than twenty years of experience defending dentists in
      malpractice situations reflects on the attitudes he typically sees in dentist
      defendants. The "professional" orientation that patients should expect nothing
      more than that the dentist does his or her best, is often at odds with the
      patient plaintiff view that they will have their feelings recognized at almost
      any price. The lawyer's role is often one of education. As the facts and
      perspectives involved are revealed through disclosure, resolutions begin to
      emerge. The best approach is for dentists to learn to communicate with patients-
      from their perspectives.

PMID- 9270219
TI  - Expert witness or "hired gun?".
AB  - The good intentions of dentists are not a protection against malpractice suits.
      The role of the expert witness in malpractice cases is to explain to judges and
      juries what the standard of care is and whether it has been followed. The
      historical practice of looking to local standards has given way to a national
      standard and the requirement that an expert be qualified and will assist the
      judge and jury in determining relevant facts. The motives of expert witnesses for
      both the plaintiff and the defense are open to scrutiny. Tort reform has begun to
      codify some of the properties of expert witness activities. Parameters of care
      may become interpreted as legally defining the standard of care. Expert witnesses
      testifying in criminal cases as forensic dentists must meet the standards of
      providing scientifically verifiable evidence passing the test of peer review.

PMID- 9270217
TI  - Malpractice--a plaintiff's perspective.
AB  - Evaluation of malpractice litigation considers any breach of the fiduciary
      responsibility of the dentist, violations of the standard of care, comparative
      patient negligence, possible defenses such as honest mistake and causation.
      Issues in determining damages and mitigation are also discussed and a series of
      questions is offered concerning evidence for various dental procedures. Emerging
      trends in litigation include disregard of manufacturers' precautionary
      instructions in using new materials.

PMID- 9270220
TI  - Ethical codes for attorneys: a brief introduction.
AB  - Ethical standards for lawyers are contained in the Model Rules of Professional
      Conduct (which lays out both "shall/shall not" rules and "may" suggestions in
      nine broad areas) and the Model Code of Professional Responsibility (which covers
      essentially the same topic areas but offers more detailed commentary). Topics
      included in the Rules are the client-lawyer relationship, the attorney's role as
      an advocate and counselor, law firms and associations, public service,
      transactions with individuals other than clients and information about legal
      services including advertising, firm names, and letterhead. The American Dental
      Association's Principles of Ethics and Code of Professional Conduct is organized
      around the five ethical principles of patient autonomy, nonmaleficence,
      beneficence, justice, and veracity. There are substantial similarities in intent
      between the ethical standards of dentists and lawyers; there are also
      differences.

PMID- 9270221
TI  - American Dental Association Division of Legal Affairs.

PMID- 9270222
TI  - Competition.
AB  - Our ambivalence toward competition can be traced to an unspoken preference for
      certain types of competition which give us an advantage over the types we value
      less. Four types are defined (a) pure (same rules, same objectives), (b)
      collaborative (same rules, shared objective), (c) market share (different rules,
      same objectives), and (d) market growth (different rules, value added
      orientation). The defining characteristics of the four types of competition are
      respectively: needing a referee, arguing over the spoils, differentiation and
      substitutability, and customer focus. Dentistry has features of all four types of
      competition, thus making it difficult to have a meaningful discussion or frame a
      coherent policy on this topic.

PMID- 9270223
TI  - Hepatitis C--a silent epidemic.

PMID- 9270224
TI  - A viable option for community hospitals: the El Dorado experience.

PMID- 9270225
TI  - Personal watercraft-related injuries in Arkansas: 1994-1996.

PMID- 9270226
TI  - Dermatologic phenomenon: clinically useful para-diagnostic pearls for everyday
      practice.

PMID- 9270227
TI  - Surgeon or system--malpractice.

PMID- 9270228
TI  - Protecting the public's health & investigating the potential for exposure: the
      BPS Chemical Company fire & explosion in West Helena.

PMID- 9270229
TI  - Radiological case of the month. Cystic adventitial disease of the popliteal
      artery.

PMID- 9270230
TI  - "Sublime anomalies": women religious and Roman Catholic hospitals in New York
      City, 1850-1920.

PMID- 9270232
TI  - From "happiness pills" to "national nightmare": changing cultural assessment of
      minor tranquilizers in America, 1955-1980.

PMID- 9270231
TI  - The development of heparin in Toronto.

PMID- 9270233
TI  - Toward family and community mental retardation services in Massachusetts, New
      England, and the United States.
AB  - Current trends in mental retardation services in the Commonwealth of
      Massachusetts were investigated using the New England region, the state of
      Michigan, and the United States as comparative frames of reference. Our goal was
      to analyze recent structural, financial, and programmatic trends in Massachusetts
      and the New England region to close state institutions and implement community
      and family support services. Massachusetts in particular illustrates the policy
      choices and challenges facing many American states engaged in restructuring their
      service delivery systems. New England is an extremely dynamic and innovative
      region that is providing significant national leadership in the provision of
      alternatives to institutional care.

PMID- 9270234
TI  - Overview and implications of Medicaid managed care for people with developmental
      disabilities.
AB  - The inclusion of people with developmental disabilities in managed care as part
      of general efforts by states to enroll and Medicaid recipients in such plans was
      reviewed. Managed care was defined and the processes by which managed care
      organizations deliver services were explained. Escalating costs and utilization
      were discussed as the primary reason for the shift to managed care. The use of
      Medicaid Section 1115 waivers by states to include Medicaid recipients was
      explored. The relation between acute health care and long-term care, and the
      utilization patterns in each, were briefly described. Finally, elements of
      managed care that are particularly important to people with developmental
      disabilities, such as care coordination, maintenance of quality, and individual
      and family support, were discussed.

PMID- 9270235
TI  - Technical elements, demonstration projects, and fiscal models in Medicaid managed
      care for people with developmental disabilities.
AB  - We presented a general model of the structure and functioning of managed care and
      described elements (provider networks, fiscal elements, risk estimation, case
      mix, management information systems, practice parameters, and quality
      improvement) critical to service delivery for people with developmental
      disabilities. A number of technical elements of managed care systems were
      delineated and reviewed in relation to the inclusion of people with developmental
      disabilities. Several managed care demonstration projects were described and,
      finally, a multi-year hypothetical budget model, including long-term care, was
      presented as a framework for considering how managed care affects specific
      service structures. Implications for people with developmental disabilities were
      discussed.

PMID- 9270236
TI  - Analysis of ethnic variations in developmental disability prevalence and
      household economic status.
AB  - Prevalence of developmental disabilities among the three largest U.S. racial and
      ethnic groups was estimated. Groups were compared on household economic status
      and access to welfare programs. Secondary analyses were conducted on 1990 and
      1991 panels of the Survey of Income and Program Participation, a nationally
      representative data base of the demographic and economic status of U.S.
      households. Estimated prevalence rate was 1.1% (June through December 1991), with
      the highest rate (1.4%) among Blacks. Households with a family member with
      developmental disabilities had significantly lower income and greater dependence
      on means-tested income support. Minority status exacerbated differences in earned
      income and access to welfare. Results were discussed in the context of general
      U.S. demographic trends.

PMID- 9270237
TI  - Personal outcomes as measures of quality.
AB  - The Council on Quality and Leadership in Supports for People With Disabilities
      (The Council), formerly known as The Accreditation Council, altered its
      definition of quality from "compliance with organizational process" to
      "responsiveness to people." Council representatives conducted focus group and
      individual meetings with people who have disabilities to identify priority
      outcomes they expect from services and supports. The 1993 Outcome Based
      Performance Measures was used in 447 interviews as part of 54 accreditation
      reviews. Staff analysis and factor analysis of the outcome interviews using a
      principle components extraction and varimax rotation resulted in 24 variables
      loading onto seven major factors (Identity, Autonomy, Affiliation, Attainment,
      Rights, Health, and Safeguards), which form the basis of The Council 1997
      Personal Outcome Measures.

PMID- 9270238
TI  - Margaret Mead and mental retardation: words of understanding, concepts of
      inclusiveness.

PMID- 9270239
TI  - Administration of medication by unlicensed assistive personnel to persons with
      mental retardation or developmental disabilities.

PMID- 9270240
TI  - Eating themselves to death: have "personal rights" gone too far in treating
      people with Prader-Willi syndrome?

PMID- 9270241
TI  - Prisoners with mental disabilities in 1692 Salem and today.

PMID- 9270242
TI  - The tobacco pouch.

PMID- 9270243
TI  - Mortality rates for respiratory disorders in Italy (1979-1990).
AB  - Trends in mortality rates for respiratory disorders were investigated in Italy
      from 1979 to 1990, using data from the Italian Central Statistical Institute
      (ISTAT). Mortality from lung cancer increased in all age groups, except for those
      aged 45-64 yrs after 1985. Respiratory diseases showed a consistent reduction; in
      particular, mortality from emphysema decreased slowly, and mortality from chronic
      bronchitis showed a significant reduction in all age groups. However, mortality
      from asthma increased markedly in all age groups up to 1985, and then levelled
      off and slightly decreased, although remaining at a higher level than in the
      1970s. In 1990, data stratified for age group and gender indicated a higher
      mortality rate in males, that tended to be age-dependent, with the highest rate
      ratio male/female in those aged 65-74 yrs. Overall, these data indicate a trend
      to increased mortality from lung cancer and asthma in Italy in the 1980s.

PMID- 9270244
TI  - Urinary endothelin excretion in patients with acute lung injury.
AB  - Increase in circulating levels of endothelin (ET), a potent vasoconstrictive and
      mitogenic endothelium-derived peptide, has been proposed as a marker of
      endothelium dysfunction in acute lung injury (ALI). In the present study, we have
      measured levels of immunoreactive ET (irET) by radioimmunoassay, in arterial
      (irETart), venous (irETven) and urine (irETur) samples obtained from 10 patients
      with ALI and 10 healthy volunteers. Arterovenous ratio, 24 h urine excretion and
      renal clearance of the peptide were calculated, to obtain indices of endogenous
      ET metabolism. The arterovenous ratio of irET was significantly higher in
      patients with ALI than in healthy volunteers (1.20 +/- 0.20 and 0.85 +/- 0.06,
      respectively; p < 0.05)). Twenty four hour urinary excretion of the peptide was
      increased in patients with ALI as compared to healthy volunteers (134.10 +/- 21.0
      and 71.70 +/- 9.30 ng.24 h-1, respectively; p < 0.001). Renal clearance of irET
      was similar in patients with ALI and healthy volunteers, indicating that the
      increase in excretion as well as in arterovenous gradient observed in patients
      with ALI was related mainly to pulmonary abnormalities of peptide handling.
      Urinary excretion of endothelin might be a useful marker of endothelial
      dysfunction occurring in acute lung injury.

PMID- 9270245
TI  - Intrapericardial administration of cisplatin in treatment of metastatic
      pericardial involvement in adenocarcinoma of the lung.
AB  - The aim of this study was to evaluate the effectiveness and side-effects of
      intrapericardial administration of cisplatin (IAC), in cases of abundant
      malignant pericardial effusion (MPE) and/or cardiac tamponade occurring in the
      course of adenocarcinoma of the lung (AL). Fifteen consecutive patients with
      abundant MPE and AL (4 females and 11 males; mean age 54 yrs) entered this
      prospective study. Following pericardiocentesis and insertion of a polyurethane
      catheter, the pericardial fluid was drained. Malignant aetiology of the
      pericardial fluid was confirmed by cytological examination. After confirmation of
      MPE, cisplatin (10 mg in 20 mL normal saline) was instilled directly into the
      pericardial space, over a period of 5 min for 3-5 consecutive days. Treatment was
      considered successful (response) if the patient survived 30 days without
      recurrence of symptoms of abundant MPE, and no other interventions directed to
      the pericardium were required. Response was achieved in 10 patients (67%). The
      mean (+/-SEM) dose of cisplatin was 56 (+/-18.9) mg. There were no complications
      related to the pericardiocentesis. Transient atrial fibrillation was detected in
      one patient. Mild nausea also occurred in one case. No hypotension or
      retrosternal pain was observed. Sclerotization of the pericardium and
      pericarditis constrictiva were detected after IAC in only one case. Cisplatin
      administered directly into pericardial space is effective and safe.
      Intraperitoneal administration of cisplatin appears to be the method of choice in
      the treatment of recurrent malignant pleural effusion in patients with primary
      adenocarcinoma of the lung. Sclerosis of the pericardial space is a very rare
      complication observed after intraperitoneal administration of cisplatin therapy.

PMID- 9270246
TI  - Intrapleural administration of recombinant interleukin-2 in non-small cell lung
      cancer with neoplastic pleural effusion.
AB  - The aim of this study was to assess the feasibility and effectiveness of
      intrapleural administration of recombinant human interleukin-2 (rhIL-2) for
      treatment of malignant pleural effusions. From May 1993 to May 1995, 21 patients
      with non-small cell lung cancer (NSCLC) and cytologically documented malignant
      pleural effusion entered the study. After complete needle drainage of the
      effusion, a dose of 9 x 10(6) international units (IU) rhIL-2 was injected
      intracavitarily. The drug was injected on the first and second day each week for
      3 weeks, in relation to the presence of effusion. Complete response (according to
      the criteria reported by Paladine st al.) was achieved in 7 of the 21 patients
      (33%), and partial response in 6 of the 21 patients (29%), with a median duration
      of 8 months (range 4-10 months). The treatment was well tolerated by all
      patients. Intracavitary administration of low-dose recombinant human interleukin
      2 in malignant pleural effusion due to non-small cell lung cancer is an effective
      and well tolerated therapeutic strategy.

PMID- 9270247
TI  - Chronic bronchopleural fistula in conservatively-treated calcified fibrothorax.
AB  - We describe two cases of a bronchopleural fistula developing in a calcified
      fibrothorax several decades after the initial pleurisy. In a follow-up lasting
      many years, the fistulae are persistent, with only minor symptoms. We suggest
      that this benign course without serious illness is due to the fact that the
      calcified shell effectively seals off the infection, and that a conservative
      approach is likely to be successful.

PMID- 9270248
TI  - Tracheal rupture secondary to orotracheal intubation.
AB  - A case of tracheal rupture due to orotracheal intubation performed for
      anaesthesiological procedures is described. It is very likely that this rare
      complication was favoured by some anatomical factors, which were responsible for
      a difficult intubation. Tracheal rupture was diagnosed by endoscopy and treated
      by a decompressive tracheostomy.

PMID- 9270249
TI  - Tuberculosis in Switzerland: from sanatorium guests to immigrants.

PMID- 9270251
TI  - Imaging of small airways disease, with emphasis on high resolution computed
      tomography.
AB  - Bronchioles are the airways less than 2-3 mm in diameter. Normal bronchioles
      cannot be reliably detected by means of high resolution computed tomography
      (HRCT). Nevertheless, in pathological cases, bronchiolar lesions can be
      identified by taking into account direct and indirect signs. On radiological
      grounds, bronchiolar lesions can be classified into four groups, on the basis of
      HRCT findings: 1) prevailing nodular opacities and "tree in bud" pattern; 2)
      consolidations or ground-glass opacities; 3) mosaic oligosemia with expiratory
      air-trapping; and 4) mixed cases. In this review, we present the main
      radiological and HRCT findings in four different entities, representing the more
      typical cases of bronchiolar pathology; bronchiolitis obliterans; bronchiolitis
      obliterans with organizing pneumonia; diffuse panbronchiolitis; and respiratory
      bronchiolitis with associated interstitial lung disease. HRCT sometimes allows a
      precise diagnosis of bronchiolar pathology; however, more often, it permits only
      a range of hypotheses to be advanced. More importantly, it allows a precise
      localization for biopsy procedures and an exact follow-up after institution of
      therapy. In normal subjects, less than 1% of the whole bronchial tree is visible
      on the standard chest radiograph. HRCT offers a good insight and invaluable
      information. New techniques, such as volumetric HRCT with sliding-thin-slab
      maximum- and minimum-intensity projections (MIP and minip) could represent an
      important additional tool in the evaluation of small airways disease.

PMID- 9270250
TI  - The current role of invasive staging in lung cancer.
AB  - Precise mediastinal lymph node staging in otherwise operable non-small cell lung
      cancer (NSCLC) is imperative as it determines subsequent treatment and prognosis.
      For mediastinal staging, even present-day computed tomography (CT) scanners have
      a low accuracy, and routine cervical mediastinoscopy is advised for precise lymph
      node assessment, certainly when considering a neoadjuvant protocol. Cervical
      mediastinoscopy remains the gold standard, and sampling of subcarinal nodes is
      essential. The role of remediastinoscopy after induction chemo- or radiotherapy
      remains to be determined. Extended mediastinoscopy is indicated to take biopsies
      of scalene lymph nodes or aorto-pulmonary nodes, which can also be reached by
      anterior mediastinoscopy. Video-assisted thoracic surgery (VATS) does not replace
      cervical mediastinoscopy but is a valid alternative to anterior or extended
      mediastinoscopy. A more complete exploration of the ipsilateral hemithorax is
      possible, with biopsies of aortopulmonary and inferior mediastinal nodes and
      judgment about resectability of the primary tumour.

PMID- 9270252
TI  - Long-term oxygen therapy: how can maximum benefit be achieved?
AB  - Domicillary long-term oxygen therapy (LTOT) is an established procedure, with
      demonstrable survival benefit. It is a complicated treatment modality and, for
      optimum cost-benefit to be attained, it must be performed well. This calls for
      careful patient selection and the selection of a suitable form of treatment for
      each individual patient. Follow-up, preferably with home care as an option, is
      also essential. No full cost-benefit analysis in economic terms has, so far, been
      presented. Even so, some suggestions can be made concerning the factors which
      need to be considered to obtain the best possible results.

PMID- 9270253
TI  - Effects of mechanical ventilation on control of breathing.
AB  - During spontaneous breathing, respiratory muscle pressure (Pmus) waveform is
      determined by a complex system consisting of a motor arm, a control centre and
      various feedback mechanisms that convey information to the control centre. In
      mechanically ventilated patients, the pressure delivered by the ventilator (Paw)
      is incorporated into the system that controls breathing and may alter Pmus, which
      in turn modifies the Paw waveform. Thus, the response of the patient's
      respiratory effort to Paw and the response of Paw to patient effort constitute
      the two components of the control of breathing during mechanical ventilation. The
      response of Paw to patient effort depends on: 1) the mode of ventilatory support;
      2) the mechanics of the respiratory system; and 3) the characteristics of the
      patient's respiratory effort. On the other hand, the response of patient effort
      to Paw is mediated through four feedback systems: 1) mechanical; 2) chemical; 3)
      reflex; and 4) behavioural. It follows that in mechanically ventilated patients
      the ventilatory output is determined by the interaction between the function of
      the ventilator and the patient's breathing control system. This interaction
      should be taken into account in the management of mechanically ventilated
      patients.

PMID- 9270254
TI  - Acute and chronic influences of obstructive sleep apnoea on the pulmonary
      circulation.
AB  - Obstructive sleep apnoea (OSA) produces immediate effects on pulmonary
      haemodynamics during sleep in all subjects. In addition, in some subjects, OSA is
      accompanied by chronic abnormalities of the pulmonary circulation. During sleep,
      pressure in the main pulmonary artery oscillates within each apnoea, in synchrony
      with intrathoracic pressure changes; in addition, it may increase progressively
      as a consequence of prolonged severe hypoxaemia. Pulmonary capillary wedge
      pressure may increase during inspiratory efforts, possibly reflecting a
      mechanical limitation of left ventricular function. Cardiac output decreases at
      apnoea resolution as an effect of a decreased right ventricular stroke volume,
      despite increased cardiac frequency. During wakefulness, postcapillary pulmonary
      hypertension occurs on exercise in many OSA patients, whilst pulmonary
      hypertension at rest is precapillary and occurs in patients with an altered
      daytime respiratory function. Development of right ventricular hypertrophy and a
      decrease in right ventricular ejection fraction appear to be related to the
      severity of respiratory alterations during sleep, whilst an overt right heart
      failure requires an altered daytime respiratory function. Long-term treatment of
      the obstructive sleep apnoea syndrome is more effective in increasing right
      ventricular ejection fraction than in decreasing pulmonary artery pressure during
      wakefulness.

PMID- 9270255
TI  - High frequency oscillatory ventilation in children and infants.
AB  - During high frequency oscillatory ventilation (HFOV), frequencies of 5-15 Hz are
      used and there are both active inspiratory and expiratory phases. Regardless of
      the type of oscillator, general principles of use can be applied, but differences
      exist between the machines regarding their waveform and mechanical efficiency. A
      high volume strategy improves oxygenation in children and infants with diffuse
      alveolar disease. In such patients, an early response indicates a favourable
      outcome; therefore, if there is no significant improvement in oxygenation after 6
      h, additional or alternative respiratory support strategies should be considered.
      HFOV can successfully support children with severe lung disease, in whom its use
      reduces chronic oxygen dependency. In near term and term infants, HFOV lessens
      the requirement for extracorporeal membrane oxygenation (ECMO), and in immature
      babies, when used appropriately, it reduces the incidence of chronic lung
      disease.

PMID- 9270256
TI  - Evolution and natural history of chronic lung disease of prematurity.
AB  - Chronic lung disease (CLD) of prematurity is a common disorder in preterm infants
      who were ventilated for respiratory distress syndrome (RDS) at birth. Premature
      birth, mechanical ventilation and supplemental oxygen are the major risk factors
      for the development of CLD. Although the exact pathophysiology is unclear, recent
      evidence suggests that pulmonary inflammation may play a pivotal role in the
      development of CLD. Histologically, the evolution of CLD can be divided into an
      early inflammatory phase followed by a subacute and chronic fibroproliferative
      phase. The early, inflammatory phase of CLD is clinically indistinguishable from
      RDS. In bronchoalveolar lavage fluid an influx of inflammatory cells and
      increased levels of cytokines can be found. Pathological examination of the lungs
      reveals persisting hyaline membranes, necrosis of airway and alveolar epithelium
      and an influx of inflammatory cells in the lung. In the subacute
      fibroproliferative or reparative phase of CLD, persistent respiratory distress
      and hypercapnia are seen and patients require oxygen with or without ventilatory
      support. Histologically, this phase is characterized by hyperplasia of type II
      pneumocytes, hypertrophy of bronchial and bronchiolar smooth muscle and
      interstitial and perialveolar fibrosis. In the chronic fibroproliferative phase
      (up to 1 yr), airway remodelling occurs. Respiratory distress continues and many
      patients remain oxygen dependent. Cyanotic spells are frequently seen and chronic
      hypoxia may lead to pulmonary hypertension and right heart failure. Many patients
      have severe feeding problems and somatic growth is poor. In surviving patients,
      persisting lung function abnormalities are found. Airway resistance and airway
      responsiveness are increased and residual volume (RV) and RV/total lung capacity
      ratios remain elevated, indicating air trapping. Although lung function improves
      during childhood, residual abnormalities are still found in young adults, raising
      concerns about the evolution of pulmonary function in old age.

PMID- 9270257
TI  - Cardiac arrhythmias in chronic obstructive pulmonary disease.
AB  - Supraventricular and ventricular dysrhythmias, as well as conduction disturbances
      of varying severity are frequently observed in chronic obstructive pulmonary
      disease (COPD). The type of arrhythmia that occurs in patients with COPD is
      influenced by their clinical state. Co-existing coronary heart disease, severe
      blood gas abnormalities and medication may precipitate the rhythm disturbances.
      Particularly in patients with acute respiratory failure, the presence of
      arrhythmias is associated with poor prognosis. However, more studies are needed
      to assess the importance of cardiac arrhythmias in stable COPD patients and their
      value in predicting survival.

PMID- 9270258
TI  - Guidelines on smoking cessation for general practitioners and other health
      professionals. European Medical Association Smoking or Health (EMASH).

PMID- 9270259
TI  - Multiple functions of alpha 1-antitrypsin and alpha 1-antichymotrypsin. 3.
      Regulation of extracellular surfactant metabolism and amyloid fibril formation.

PMID- 9270260
TI  - Chemotherapy of non-small cell lung cancer.

PMID- 9270261
TI  - Candidate locus approach for studying the genetics of asthma and atopy.
AB  - Insights into the complex genetic factors underlying asthma and atopy have arisen
      from investigating genes whose functions are likely to be involved in the
      pathogenesis of these disorders. Candidate genes have now been studied on 13
      human autosomes, and genetic linkage analysis and association studies have
      identified potentially important genes on chromosomes 5, 6, 11 and 14. However,
      these four regions do not account for all the heritability of these disorders,
      and additional regions are now being identified by systematic searches of the
      whole genome.

PMID- 9270262
TI  - Peripheral muscle function in COPD.

PMID- 9270263
TI  - Survival in patients receiving long-term home oxygen therapy.

PMID- 9270264
TI  - The cost-effectiveness of four cisplatin-containing chemotherapy regimens in the
      treatment of stages III B and IV non-small cell lung cancer: an Italian
      perspective.

PMID- 9270265
TI  - Relationship between atypical adenomatous hyperplasia (AAH), prostatic
      intraepithelial neoplasia (PIN) and prostatic adenocarcinoma.
AB  - Two histopathologic lesions are considered putative precursors of prostate
      cancer, but the supportive evidence for one (prostatic intraepithelial neoplasia,
      or PIN) is much greater than the other (atypical adenomatous hyperplasia, or
      AAH). High grade PIN is the most likely precursor of carcinoma, arising in the
      peripheral zone, but probably does not account for well-differentiated cancer
      arising in the transition zone. The biological significance of atypical
      adenomatous hyperplasia of the prostate (AAH) is inconclusive at the time. The
      histological and cytological features of AAH are intermediate between BPH and low
      grade carcinoma, suggesting that AAH may be a precursor of well differentiated
      transition; zone carcinoma. In the recent time new findings on morphogenetic
      aspects of normal and abnormal prostatic growth i.e. stem cell models are
      discussed and topics about grading and proliferative activities, frequency and
      histological changes associated with aging as well as clinical relevance of PIN
      and AAH. This paper reviews the results and discussion at the second
      international consultation meeting on PIN in Mayo Clinic, Rochester, Nov. 3-4 th.
      1995, following the first international consultation meeting of AAH and PIN and
      origin of the prostatic carcinoma in Ancona, Sept. 11-12 th 1994.

PMID- 9270266
TI  - Medullary and mixed medullary-papillary carcinoma of the thyroid gland.
AB  - Concurrent medullary and papillary carcinomas of the thyroid gland are rare and
      occurrence of the medullary and medullary-papillary carcinoma, as far as we know,
      has not been previously described. The medullary carcinoma was found in the upper
      part of the right lobe and the mixed medullary-papillary carcinoma in the left
      lobe of thyroid gland. Immunohistochemistry revealed calcitonin positivity in the
      medullary parts of the carcinoma and thyroglobulin positivity in papillary
      structures. Both light microscopy and immunohistochemistry observation
      distinguished these two cell lineages. The patient was treated with radiotherapy
      but died 18 months after first symptoms. Metastases were identified in the liver,
      mediastinal lymph nodes and soft tissues and micro-metastases in the lungs. The
      authors discuss histogenesis of mixed thyroid carcinomas.

PMID- 9270267
TI  - Portrait of an American surgeon: Thomas Eakins's the Gross Clinic.

PMID- 9270268
TI  - A bloody mess: a commentary on the Gross Clinic.

PMID- 9270269
TI  - Mentoring physician-scientists: fear of the unknown and scientific opportunity.

PMID- 9270270
TI  - The borderland: a medical clerkship in Bombay.

PMID- 9270271
TI  - Doctors and patients: facing life-threatening illnesses.

PMID- 9270272
TI  - Vitruvian man: metaphor of a "compleat" physician.

PMID- 9270273
TI  - An old man's story.

PMID- 9270274
TI  - Terrible death of Socrates: some medical and classical reflections.

PMID- 9270275
TI  - Judgment day and a woman named Myrtle.

PMID- 9270276
TI  - An entry-level question.

PMID- 9270277
TI  - Canna Lily.

PMID- 9270278
TI  - Finding one's way in medicine.

PMID- 9270279
TI  - Physician objectivity.

PMID- 9270280
TI  - Event medicine and attendance medicine.

PMID- 9270281
TI  - Physicians' income--up or down?

PMID- 9270282
TI  - Fostering science and science careers.

PMID- 9270283
TI  - Mobilizing for child health and well being.

PMID- 9270284
TI  - Nursing case management and its role in perinatal risk reduction: development,
      implementation, and evaluation of a culturally competent model for African
      American women.
AB  - The authors outline the need for comprehensive perinatal services management for
      African American pregnant women, based on social/environmental stressors, and
      propose a workable model for delivery of services based on case management
      principles. The implications of case management as an intervention to ameliorate
      these stressors are discussed. Data from 5 years of comprehensive case management
      are included to support the effectiveness of case management as an intervention
      among high-risk women. Steps utilized to develop, implement, and evaluate case
      management are also discussed.

PMID- 9270285
TI  - The retirement transition and the later life family unit.
AB  - The purpose of this investigation was to determine to what extent family
      worldview and problem-solving communication style influence individual and family
      unit adaptation during retirement. A cross-sectional correlational survey design
      utilized Pearson correlations and stepwise multiple regressions. The sample
      consisted of 368 individuals representing 184 later life family units.
      Operationalized as family unit data, family worldview and family problem-solving
      communication style were examined in two series: (1) with outcome variable of
      family unit adaptation and (2) with outcome variable of individual adaptation.
      Scoring of family unit data was conceptually, procedurally, and analytically
      congruent. The investigation extended McCubbins' work into the later life family
      unit giving empirical support for two propositions of the Resiliency Model (M.A.
      McCubbin & H.I. McCubbin, 1993). This investigation also extended A. Antonovsky's
      (1987) work as the second study to apply the Antonovsky Sense of Coherence Scale
      to a family measurement. Conclusions are that although the way the family views
      the world is important during retirement, being affirmed by family members is
      more important. The investigation highlights the importance of a positive problem
      solving communication style for a positive level of family adaptation. Individual
      adaptation during retirement was more influenced by family worldview.

PMID- 9270286
TI  - Giving voice to elderly people: community-based long-term care.
AB  - Information gained from elderly people regarding their needs for community-based
      long-term care is necessary for informed and responsive policy development.
      Informed policy development is essential given demographic projections and the
      need to develop cost-effective alternatives to institutionalization. The purpose
      of this study was to understand the context within which elderly people would be
      able to continue residing in their communities. Programs have been developed
      based on providers' perceptions of services that are necessary to maintain
      elderly people at home. There is a lack of information about elderly people's
      perceptions. Data were collected from 9 elderly people who represented the
      phenomenon of being at risk for institutionalization. Participants were
      interviewed serially and contingently in stages using naturalistic methodology.
      The interviews were tape-recorded, transcribed verbatim, and analyzed by the
      inquirer. Findings of the study indicated that the desire of elderly people to
      stay at home is motivated by their need to maintain control over their daily
      lives and have their individualized needs addressed. Perceptions related to
      nursing homes, roles of family, essential services, and future needs for assisted
      living emerged as major themes. The findings suggest policy implications for
      professional nurses related to the long-term care system, providers, and nursing
      homes.

PMID- 9270287
TI  - Effects of parity and weaning practices on breastfeeding duration.
AB  - The purpose of this project was to examine (a) patterns of breastfeeding and (b)
      duration with parity and breastfeeding experience, and (c) mothers' reasons for
      termination of breastfeeding. A convenience sample of 120 breastfeeding mothers
      was followed by home visits and telephone for 20 weeks after delivery. The sample
      consisted of 69 primiparas, 40 multiparas with previous breastfeeding experience,
      and 11 multiparas with no prior breastfeeding experience. Parity was not
      significantly associated with the continuation of breastfeeding but there was a
      trend toward a difference made by breastfeeding experience. Inadequate milk
      supply and employment were the two most common reasons reported for weaning.
      Implications for support in the workplace and for first-time breastfeeding
      mothers are discussed.

PMID- 9270288
TI  - Focus groups among public, military, and private sector mothers: insights to
      improve the immunization process.
AB  - The underimmunization of children younger than 2 years old is a major health
      problem in U.S. cities. Innovative methods to increase immunization rates are
      being researched and implemented. In 1993, six focus groups were conducted with
      41 mothers (25 African Americans and 16 Caucasians) to discuss their views
      regarding immunizations and the services they received from health care providers
      in the public health (n = 27), military (n = 4), and private (n = 10) sectors.
      Participants viewed immunizations positively, but perceived many barriers to
      immunization. They suggested the following ways to improve the immunization
      process: enhancing knowledge acquisition, improving reminder and appointment
      systems, providing transportation and child care, decreasing waiting times,
      improving the clinic environment, and making the immunizations less traumatic.
      According to mothers in this study, obtaining an immunization on time is a
      complex task that requires planning and resources. The fewer resources that are
      available to mothers, the more difficult it is to succeeded. Health care
      providers must help mothers identify and remove barriers if immunization rates
      are to be increased.

PMID- 9270289
TI  - Resource use by abused women following an intervention program: associated
      severity of abuse and reports of abuse ending.
AB  - Although violence against women is recognized as major public health problem,
      little is known about the effectiveness of interventions. To evaluate severity of
      abuse and use of community resources following an intervention program, 132
      pregnant abused women received three counseling sessions in a prenatal setting. A
      comparison group of 67 abused women were offered a wallet-sized card listing
      community resources for violence. Resource use, severity of abuse, and reports of
      the abuse ending were measured for both groups at 6 and 12 months after delivery.
      Resource use was significantly (p < .001) related to severity of abuse,
      irrespective of whether the woman had received the intervention. Women using
      resources at 6 months were also users at 12 months. These findings indicate a
      "survivorship model" whereby abused women assertively and persistently seek a
      variety of community resources to end the abuse. The recommendation that primary
      care providers go beyond traditional identification and referral for abuse to
      coordination and evaluation of service delivery is discussed.

PMID- 9270290
TI  - Cervical cancer screening practices among Latino women in Chicago.
AB  - Previous studies have determined that Latino women, especially Mexican women,
      have the lowest rates of cancer-screening practices of any racial and ethnic
      group in the United States (L. S. Caplan, B. L. Wells, & S. Haynes, 1992; L. C.
      Harlan, A. B. Bernstein, & L. G. Kessler, 1991). The purpose of this descriptive
      study was to identify factors associated with irregular Papanicolaou (Pap)
      screening among Latino women. The convenience sample consisted of 111 Mexican and
      Puerto Rican women ages 40 and older, recruited through two inner-city clinics,
      located in two major Latino communities in Chicago. The women were interviewed
      face-to-face by trained bilingual interviewers, using a structured questionnaire.
      Mexican ethnicity and older age were found to be associated with irregular
      cervical cancer-screening practices. These results suggest that interventions
      need to be developed for educating Latino women about the purpose and importance
      of Pap test-screening practices. Further research is needed to examine other
      barriers that impede these women from using cervical cancer-screening services.

PMID- 9270291
TI  - Vascular damage and not hypertension per se influences endothelin-1 plasma levels
      in patients with non insulin dependent diabetes mellitus.
AB  - Several reports indicate higher endothelin-1 (ET-1) levels in patients with non
      insulin dependent diabetes mellitus (NIDDM), although this finding has not been
      confirmed by other studies. The discrepancy may be partially explained by the
      frequent coexistence in NIDDM patients of other pathologies, such as essential
      hypertension, and by the presence of diabetic vascular complications or renal
      failure, able, per se, to increase ET-1 circulating levels. This study aimed to
      evaluate the influence of arterial hypertension and/or of diabetic angiopathy on
      ET-1 circulating levels in a group of NIDDM patients. We measured ET-1 plasma
      concentrations in three groups of subjects: a) 22 NIDDM patients with or without
      hypertension and with or without vascular complications; b) 11 hypertensive
      patients; c) 14 age-matched healthy volunteers. Plasma ET-1 concentrations were
      significantly higher in NIDDM patients with angiopathy (7.3 +/- 0.7 pg/ml, mean
      +/- Standard Error; p < 0.001) than diabetics without angiopathy (4.4 +/- 0.53
      pg/ml), hypertensive patients (4.7 +/- 0.85 pg/ml) and healthy subjects (3.1 +/-
      0.19 pg/ml). This report indicates that increased plasma ET-1 levels in NIDDM
      patients may be ascribed only to those with vascular compliances, while
      hypertension, per se, does not affect ET-1 plasma levels in these patients.

PMID- 9270292
TI  - Serum beta-endorphin increase after intravenous histamine treatment of chronic
      daily headache.
AB  - Histamine is able to induce spontaneous-like headache attacks in migraine and
      cluster headache subjects. Therefore, it has been considered as a possible agent
      in the pathogenesis of headache. Histamine desensitization is used for the
      treatment of cluster and other chronic headaches like migrains with
      interparoxysmal headache. However, it is unknown whether desensitization plays a
      role in headache improvement. Since a disfunction of the opioid system has been
      considered responsible for idiopathic headache and since low beta-endorphin
      levels have been demonstrated in some idiopathic headaches, particularly in
      migraine with interparoxysmal headache, we planned this study to verify if
      histamine therapy is able to modify serum beta-endorphin concentrations. For this
      purpose, we studied 24 healthy control subjects and 36 patients suffering from
      migraine with interparoxysmal headache refractory to conventional therapies.
      Patients showed baseline serum beta-endorphin levels significantly lower than
      healthy control subjects and treatment with histamine for 15 days increased their
      beta-endorphin concentrations. We believe that histamine treatment can activate
      the opioid endogenous system. However, the therapeutic effect of histamine
      remains to be verified by evaluating the correlation between beta-endorphin
      levels and headache improvement.

PMID- 9270293
TI  - Solitary extramedullary plasmacytoma.
AB  - A rare case of abdominal plasmacytoma is described. A computed guided biopsy of
      abdominal mass permitted an accurate diagnosis. Blood findings revealed an
      increased gamma-globulin level and serum immunoelectrophoresis revealed high IgG
      kappa spike. Bone marrow biopsy resulted negative for neoplastic infiltration.
      Plasmacytoma is a malignant proliferation of differentiated B lymphocytes which
      produce immunoglobulin. In our case, microscopically, biopsy of abdominal mass
      revealed the presence of plasmablasts with bizarre multiforme nuclei, spindled
      contours and positive immunoenzymatic reaction for CD38, suggestive for plasma
      cell proliferation.

PMID- 9270294
TI  - [Expression of cluster of differentiation CD28 at different age].

PMID- 9270295
TI  - On cabbages and kings: the IUBMB--problems and prospects.

PMID- 9270296
TI  - Centenary of the birth of modern biochemistry.

PMID- 9270297
TI  - Hydrogen exchange at equilibrium: a short cut for analysing protein-folding
      pathways?
AB  - Hydrogen exchange is an attractive method for observing small populations of
      partly unfolded states of proteins at equilibrium. It has been suggested that
      these represent folding intermediates so that hydrogen exchange can offer a short
      cut for studying protein-folding pathways. This cannot work in theory because it
      is not possible to tell whether they are intermediates or side reactions.
      Experimental studies of barnase and chymotrypsin inhibitor 2 show that there is
      no obvious relationship between hydrogen exchange at equilibrium and their
      folding pathways.

PMID- 9270298
TI  - Why do protein kinase cascades have more than one level?

PMID- 9270299
TI  - How responses get more switch-like as you move down a protein kinase cascade.

PMID- 9270300
TI  - Glutamate dehydrogenase: an organelle-specific mRNA-binding protein.

PMID- 9270301
TI  - Molecular intimacy between proteins specifying plant-pathogen recognition.
AB  - Disease resistance in plants is commonly specified by genetically paired plant
      resistance (R) and pathogen avirulence (Avr) proteins. Recent molecular analyses
      of several R-Avr protein interactions provide compelling evidence for a receptor
      ligand mechanism in which specific binding of the Avr elicitor by its matching R
      protein leads to activation of the plant defence response. Direct R-Avr protein
      recognition precedes the function of an expanding battery of plant resistance
      signalling components.

PMID- 9270302
TI  - Cytoplasmic signalling domains: the next generation.
AB  - Since the late 1980s, when Src-homology SH2 and SH3 domains were identified, the
      repertoire of non-catalytic signalling domains has increased to number over 30.
      As it is expected that further regulatory domains shall be found, unravelling the
      complex network of their interactions remains an on-going challenge.

PMID- 9270303
TI  - Caspases: killer proteases.
AB  - Caspases (cysteinyl aspartate-specific proteinases) mediate highly specific
      proteolytic cleavage events in dying cells, which collectively manifest the
      apoptotic phenotype. The key and central role that these enzymes play in a
      biochemical cell-suicide pathway has been conserved throughout the evolution of
      multicellular eukaryotes.

PMID- 9270304
TI  - Distinct and specific functions of cGMP-dependent protein kinases.
AB  - cGMP-dependent protein kinases I and II conduct signals from widespread signaling
      systems. Whereas the type I kinase mediates numerous effects of natriuretic
      peptides and nitric oxide in cardiovascular cells, the type II kinase transduces
      signals from the Escherichia coli heat-stable enterotoxin, STa, and from the
      endogenous intestinal peptide, guanylin, stimulating Cl- conductance of the
      cystic fibrosis transmembrane conductance regulator (CFTR). Although the two
      kinases may be interchangeable for several functions, CFTR regulation
      specifically requires the type II kinase.

PMID- 9270305
TI  - Methods and reagents. Chemiluminescent detection methods.

PMID- 9270306
TI  - Cn3D: a new generation of three-dimensional molecular structure viewer.

PMID- 9270307
TI  - New PC versions of the kinetic-simulation and fitting programs, KINSIM and
      FITSIM.

PMID- 9270308
TI  - The in vitro biosynthesis of an authentic protein.

PMID- 9270309
TI  - Declaration of Olympia on nutrition and fitness. Ancient Olympia, Greece, May 28
      29, 1996.

PMID- 9270310
TI  - Energy costs of physical activity.

PMID- 9270311
TI  - Pre-exercise food intake and performance.

PMID- 9270312
TI  - Fat as a fuel for exercise.

PMID- 9270313
TI  - Aspects of dehydration and rehydration in sport.

PMID- 9270314
TI  - Exercise, muscle metabolism and the antioxidant defense.

PMID- 9270315
TI  - The 'Are' Sport Nutratherapy Program: the rationale for food supplements in
      sports medicine.

PMID- 9270317
TI  - Body perception and emotional health in athletes: a study of female adolescents
      involved in aesthetic sports.

PMID- 9270316
TI  - Micronutrients: effects of variation in [Hb] and iron deficiency on physical
      performance.

PMID- 9270318
TI  - Intervention strategies and determinants of physical activity and exercise
      behavior in adult and older adult men and women.

PMID- 9270319
TI  - Determinants of physical activity in children.

PMID- 9270320
TI  - Some nutritional parameters in adolescent females suffering from obesity or
      anorexia nervosa: a comparative study.

PMID- 9270321
TI  - Do plasma polyunsaturates predict hostility and depression?

PMID- 9270322
TI  - Physical activity in the prevention and management of cardiovascular disease.

PMID- 9270323
TI  - Physical activity in the prevention of non-insulin-dependent diabetes mellitus.

PMID- 9270324
TI  - Physical activity in the prevention and management of obesity.

PMID- 9270326
TI  - Physical activity in the prevention and management of cancer.

PMID- 9270325
TI  - Physical activity, long-term CHD mortality and longevity: a review of studies
      over the last 30 years.

PMID- 9270327
TI  - Importance of dietary fat in modulating PGE2 responses and influence of vitamin E
      on bone morphometry.

PMID- 9270328
TI  - Serum protein polymorphisms in seven populations from Middle Eastern and Eastern
      Europe.
AB  - Serum specimens from 1385 unrelated males and females from seven Middle East and
      East European sample surveys (Prague, Olomouc, Krakow, Poznan, Szeged, Moscow,
      and Jekaterinburg) have been typed for seven polymorphic serum protein
      polymorphisms (GC, TF, PLG, PI, A2HS, F13B, and ITI). The distributions of
      phenotype and allele frequencies show a marked heterogeneity, especially with
      regard to the allel GC*1F of the GC system, the alleles A2HS*1 and A2HS*2 of the
      A2HS system and the alleles F13B*1 and F13B*3 allele of the F13B system. Analysis
      of the genetic variability by means of distance and principal component analysis
      revealed that with regard to the seven polymorphic loci studied the population
      samples from Prague and Jekaterinburg are characterized by deviating genetic
      structures. While the different genetic structure of the sample from Prague is
      mainly due to the distribution of the alleles at the A2HS locus, the sample from
      Jekaterinburg shows differences in several loci. The genetic dissimilarity
      corresponds to the large geographic distance from the other populations and can
      presumably be explained with the comparatively heterogeneous ethnic composition
      of the population of this city located at the geographic borderline between
      Europe and Asia.

PMID- 9270329
TI  - Characteristics of Japanese, Korean, and Chinese populations based on the genetic
      markers of human immunoglobulins.
AB  - A description of the population groups in the three adjacent countries Japan,
      Korea and China has been made on the basis of the genetic markers of human
      immunoglobulins under consideration fo their characteristics and formation.

PMID- 9270330
TI  - Spatial autocorrelation analysis reveals that A, B and O allele frequency
      surfaces on the Indian subcontinent are highly fractured.
AB  - Spatial autocorrelation analysis performed on published data pertaining to caste
      and tribal populations of the Indian subcontinent has revealed that the surfaces
      of A, B and O allele frequencies are highly fractured. The only significant
      spatial autocorrelation was observed in respect of the A allele frequency among
      caste populations.

PMID- 9270331
TI  - Genetic studies in a North-Slovakia isolate: Chmelnica. 3. Dermatoglyphic traits.
AB  - Dermatoglyphic traits in an endogamous community of the village Chmelnica (North
      Eastern part of Slovakia) are reported and their frequency is compared with an
      average Slovak population. The results of this study demonstrate the regional
      variability and the particular dermatoglyphic specificity of the investigated
      population. The most conspicuous are the increased intergender differences in the
      course of the main lines on the palms, their consequently higher quantitative
      expression by indices, and the higher quantitative values of total line numbers
      on fingers that was observed for females of our sample.

PMID- 9270332
TI  - Anthropometric affinities among the 20 endogamous groups of Dhangars of
      Maharashtra, India.
AB  - Fourteen anthropometric measurements were used to examine the affinities among 20
      Dhangar castes of Maharashtra, in a sample of 2437 adult males. The results are
      interpreted in the light of their ethnohistorical and geographical backgrounds on
      the one hand and with reference to the affinities observed on the basis of other
      biological variables, different sets of qualitative and quantitative
      dermatoglyphic variables and genetic markers, on the other. The configuration of
      anthropometric distances is largely conformatory to the geographical backgrounds
      of the groups, and there is no significant correspondence with the dendrograms
      based on the other sets of variables which are mutually independent among them.

PMID- 9270333
TI  - A longitudinal study of biological changes with age among the Brahmins of
      Calcutta.
AB  - In this paper, the individual biological sequence of change with age in a sample
      taken in metropolitan city, Calcutta, West Bengal, is discussed. The study
      comprises a few anthropometric measurements (stature, weight, biacromial breadth,
      nasal length, nasal breadth, upper facial height) taken on the same population at
      an interval of five years (first in the year 1982 and again in the year 1987).
      The study reveals that the amount of increment or decrement of some characters
      (the above mentioned traits) are different for different chronological age; and
      these differences can only be identified with the help of a longitudinal study
      which is free from the effect of secular change in the younger generations.

PMID- 9270334
TI  - Secular changes of body height and mass in the children and adolescents of Lodz.
AB  - The report illustrates secular changes in the development of body height and mass
      in Lodz school children and youths in a period of time covering 65 years between
      1930-1994. The lowest values of both traits were found in the early post-war
      period (1948-1949) increasing gradually until the end of the seventies. From that
      time the secular trend diminished successively, restraining completely in the
      last years (1992-1994). This seems to be connected with the economic crisis of
      the eighties in Poland, and the deep transformation of socio-economic relations
      in the last several years. According to the secular changeability values, the
      rate of that process in relation to younger groups of children increases
      considerably from the 12th year of life. The biggest changes (in centimeters and
      kilograms per decade) can be observed in the age of 15 and 16 years. Usually more
      distinctive variableness is apparent in boys than in girls.

PMID- 9270335
TI  - Variations in the formation of the cardiac plexus--a study in human foetuses.
AB  - The origin and distribution of nerves forming the cardiac plexus and the
      subdivision of this plexus were studied in six human foetuses (2 male, 4 female)
      of gestational ages 30 to 40 weeks. The cardiac plexus was not divided into
      superficial and deep parts in any foetus. True plexiform arrangement of nerves
      forming the cardiac plexus was seen only after the nerves reached the walls of
      the heart. The sympathetic trunks, vagi, recurrent laryngeal nerves and phrenic
      nerves of both sides contributed to the cardiac plexus. The cervical sympathetic
      trunk showed only two ganglia bilaterally in one foetus; this has not been
      reported before. In one foetus on the right side, the middle cervical sympathetic
      cardiac branch joined the recurrent laryngeal and the phrenic nerves which has
      not been reported earlier. The sympathetic pathways to the heart were found to be
      very variable; no two foetuses showed the same arrangement. Awareness of these
      variations in the nerves forming the cardiac plexus would enhance the success of
      sympathectomy to augment cardiac blood flow or to relieve the severity of cardiac
      pain.

PMID- 9270336
TI  - Formation of morphological traits of the quadriceps femoris muscle (QFM) before
      and after birth. Part I. Rectus femoris muscle (RFM).
AB  - Studies on the formation of morphological traits of the quadriceps femoris muscle
      were carried out on the material of 138 human fetuses (70 males and 68 females),
      9-36 weeks old, and 50 adults (33 male, and 17 female). Some intermediary
      conclusions were drawn for probable changes occurring in the morphological
      formation of the muscle after birth by comparing proportions of the muscle at the
      fetal stage with its form in adults. In this research, anthropometric methods and
      statistical analysis of results have been applied. The analysis of the results in
      the fetal group has shown that all metrical characteristics of the muscle reach
      their maximum values at the end of the investigated ontogenetic period. This is,
      naturally, a consequence of the development and growth of all fetal body
      measures, including an elongation of the thigh. Yet, the development of the
      individual muscle characteristics is not regular and although the trend of this
      growth is similar, its extent varies, and differs slightly in the two sexual
      groups. A comparison of the values of muscle indices for 9 month old fetuses with
      the same indices for adults shows that the relative dimensions of all
      investigated muscular characteristics decrease during the post-natal period
      except the relative length of the tendon.

PMID- 9270337
TI  - Genetic diversity of PTC taste sensitivity among tribal and caste populations of
      Andhra Pradesh, India.
AB  - The present paper reports the variability of PTC taste sensitivity among eight
      endogamous tribal populations inhabiting the Eastern Ghats of North Coastal
      Andhra Pradesh. It was compared with the genetic diversity of PTC taste
      sensitivity among tribal and caste populations of Andhra Pradesh. The tribal and
      caste groups present a relatively high genetic diversity, of which a major
      proportion is due to genetic differences within populations rather than that
      between populations. Castes show a higher heterogeneity than tribes, the
      difference being significant. The high genetic diversity found among Andhra
      populations may be attributed to social stratification and the practice of strict
      endogamy.

PMID- 9270339
TI  - Subjective responses to light sources of different colour temperatures and
      illuminances.
AB  - User attitudes towards certain lighting conditions have as yet been predominantly
      a field of lighting engineering research, aiming at an optimisation of lighting
      conditions on the basis of averages. Therefore, data on the interindividual
      variability of subjective responses hardly exist. In contrast to this, the
      methodological approach of industrial anthropology is based on the consideration
      of individual variation to provide basic data which are required to design our
      dwelling environment. Against this background we simulated an office work
      situation in the light laboratory and-using semantic differentials-studied
      subjective responses to four different lighting conditions in which different
      illuminance levels were combined with different colour temperatures of the light
      source. Colour temperature is an aspect of artificial illumination that has
      rarely been considered in lighting studies. The results of our study indicate
      that (1) subjective judgements of the four lighting situations differ
      significantly, (2) relatively long, repeated exposures of test participants to
      lighting situations lead to a change of attitudes, and (3) subjective judgements
      and preferences show a considerable interindividual variation. These results
      suggest that lighting designs of office rooms that are merely orientated towards
      averages are inadequate and support lighting concepts that allow for individually
      adjustable light sources.

PMID- 9270338
TI  - Serum levels of sex hormones, thyroid hormones, growth hormone, IGF I, and
      cortisol and their relations to body fat distribution in healthy women dependent
      on their menopausal status.
AB  - The relations between 10 anthropometric variables describing the amount of
      adipose tissue and the serum levels of thyroxine, triiodothyronin, thyroid
      stimulating hormone, estradiol, progesterone, 17-hydroxyprogesterone, prolactin,
      luteinizing hormone, follicle stimulating hormone, DHEA-S, androstendion,
      testosterone, sex hormone binding globulin, growth hormone, IGF I as well as
      cortisol were investigated in 39 premenopausal and 38 postmenopausal women.
      Several statistically significant correlations between hormonal parameters and
      the amount and the distribution of subcutaneous fat tissue were found for the
      premenopausal group. The postmenopausal probands, however, showed fewer
      statistically significant connections between the two trait systems. The
      correlation patterns in both proband groups resembled each other. Only with
      regard to the gonadotropines (LH and FSH) a difference in the algebraic sign of
      the correlation coefficients can be observed for pre- and postmenopausal
      probands. The multiple regression analysis corroborated the hypothesis that
      hormonal parameters are responsible for somatic changes after menopause.

PMID- 9270340
TI  - A comparative study of medetomidine-butorphanol-ketamine and medetomidine
      ketamine anaesthesia in dogs.
AB  - The anaesthetic and cardiopulmonary effects of medetomidine (20 micrograms/kg)
      butorphanol (0.1 mg/kg)-ketamine (MBK) (2.5, 5.0, 7.5 mg/kg) and medetomidine (40
      micrograms/kg)-ketamine (5.0 mg/kg) (MK) were compared in dogs. The induction
      time (time from the initial injection of the sedative to lateral recumbency) by
      medetomidine-butorphanol (6.0 +/- 2.3 min) was significantly shorter than that by
      medetomidine alone (10.4 +/- 2.9 min). The duration of anaesthesia induced by MK
      was shorter than that by MBK2.5. The analgesic effects of MBK were more potent
      than those of MK. Mean arterial blood pressure increased significantly after
      administration of the sedatives, and then decreased to base-line value after the
      ketamine injection and remained stable throughout the experimental period.
      Respiratory rate decreased gradually after the administration of each sedative
      and was depressed until 60 min after the ketamine injection. MBK anaesthesia is
      effective and widely available for therapeutic procedures depending upon the
      selection of the ketamine dose.

PMID- 9270341
TI  - A comparison of serum ionized calcium concentrations and serum total calcium
      concentrations in dogs with lymphoma.
AB  - Serum ionized calcium and total calcium concentrations were measured in 16 dogs
      with lymphoma and 49 healthy control dogs. Blood samples for all determinations
      of ionized calcium were collected into tubes containing silicone separator gel
      and processed under a closed anaerobic system. An ionized calcium analyser with
      ion selective electrodes was used to determine pH, ionized calcium and ionized
      calcium adjusted to pH 7.4. Reference ranges for ionized calcium (iCa pH 7.4) of
      1.30-1.46 mmol/l, and for total calcium of 2.37-2.82 mmol/l were established. A
      stronger correlation (r = 0.85) was found between measured ionized calcium and
      total calcium levels in dogs with lymphoma and hypercalcaemia than in those with
      lymphoma and normocalcaemia (r = 0.64). Measurement of serum ionized calcium was
      diagnostically concordant with the measurement of serum total calcium in the
      determination of calcium status in all dogs with lymphoma. Serum ionized calcium
      did not provide a diagnostic advantage over total calcium in the detection of
      hypercalcaemia of malignancy in these dogs.

PMID- 9270343
TI  - Morphology of starch digestion in the horse.
AB  - Structure of starch in feed and chyme of horses (7 with a cannula at the caudal
      end of the jejunum and 2 with a cecal fistula) after feeding high starch diets
      (maize: whole, broken, ground, expanded and as silage, oats: whole, rolled or
      ground, rolled barley, raw potatoes, and tapioca) was investigated by light and
      electron microscopy. Structure of feed starch and morphology or starch
      degradation in the chyme corresponded to data on preileal starch digestibility
      which was investigated in a parallel study. Barriers for starch digestion in the
      gastrointestinal tract of the horse were structure of the plant storage organ, as
      for example, a tight connection between starch granules in maize gains as well as
      the structure of the starch granules itself. The highly digestible oat starch was
      degraded by exocorrosion around the grains, whereas in other, less digestible,
      starch types degradation occurred by endocorrosion via pin holes. The number and
      size of the pin holes increased with increasing preileal starch digestibility.
      The effect of various ways of decomposition on preileal digestibility increased
      with advanced destruction of the original starch structure. Expanding was most
      effective. The granules were destroyed completely and the starch became soluble.
      Simple examination by light microscopy is a fast method to evaluate the degree of
      starch decomposition in the feed.

PMID- 9270342
TI  - The effect of neomycin on the kidney function of the horse.
AB  - The toxic effect of neomycin on the horse kidney was studied. Twelve horses were
      used, and were divided at random into three groups of four. The first group was
      treated twice a day with 10 mg/kg I.M. for 15 days and then euthanised; kidney
      and liver samples were studied and no histopathological changes were observed.
      Group 2 was treated with neomycin sulphate as in group 1, and group 3 was used as
      control. Blood samples were taken at 8.00 h and 20.00 h daily from both neomycin
      treated and control horses. Serum creatinine, potassium, sodium and urinary
      creatinine remained without change. On day 6 of treatment plasma urea (Urea)p
      decreased to 5.6 +/- 2.0 mmol/L (P < 0.001) as compared with controls (8.0 +/- 2
      mmol/L). Urinary excretion of GGT increased on the third day of treatment to
      118.6 +/- 1 IU/L for treated and 89 +/- 8 IU/L for controls (P < 0.001).
      Thereafter, GGT continued to be elevated significantly for the duration of the
      experiment, as compared with controls. The (GGT)/(Cr)u ratio increased
      significantly on the 9th day of treatment, and continued to be elevated for 6
      days after treatment. Neomycin kinetics were similar during treatment. It was
      concluded that neomycin, in the dose used, was not harmful to kidney function in
      the horse.

PMID- 9270344
TI  - The effects of age and reproductive status on serum and blood parameters in
      merino breed sheep.
AB  - Merino breed female sheep (225 in total) were used to study the effects of age
      and reproductive state on the values of 31 physiological parameters. Of these 31
      parameters, 23 were affected by the age of animals, by their reproductive state,
      or by the interaction between these two factors. The statistical weighing of each
      of the factors of variability was determined. This revealed that the effects
      produced by them were indeed systematic. In order to demonstrate the systematic
      nature of the factors of variability, an attempt was made to classify each animal
      with respect to its reproductive state and age group, given only the set of
      biochemical values relating to it. The number of correct assignments to an age
      group achieved was 84.41%, and this rose to 92.17% with regard to reproductive
      state. A figure of 100% of correct assignments was reached with the adult age
      group and animals in oestrus. Thus, although the range of values observed for
      physiological parameters can, on occasions, be very large, this must be seen as a
      result of physiological deviations from average. These deviations are systematic
      and quantifiable, whether analysed in isolation or together as part of a
      multivariate analysis.

PMID- 9270345
TI  - A retrospective study of the inheritance of peromelia in Angora goats.
AB  - Peromelia, agenesia of the distal parts of the limbs, has been reported as a
      congenital defect in several animal species. In Angora goats, cases occur in a
      familiar pattern consistent with an autosomal recessively inherited defect. To
      obtain further evidence on the inheritance of peromelia in Angora goats, breeding
      results for goats being daughters of known carriers and which were then mated to
      a known carrier were analysed. Of 45 kids born in 1993 and 1994, five kids had
      peromelia. This corresponded to the expected 7:1 segregation. The difference
      between the number of affected male and female kids was not statistically
      significant. Peromelia affected kids occurred significantly more frequently among
      goats selected in the breeding study than among other goats in the respective
      herds. The study demonstrated that peromelia is inherited as an autosomal
      recessive defect. Based on knowledge obtained in a previous study, the genotype
      probably has varying degrees of expressivity.

PMID- 9270346
TI  - A scanning electron microscope study of the structural component of the bovine
      vaginal fluid at oestrus.
AB  - The ultrastructure of the vaginal fluid of cows at oestrus was analysed by
      scanning electron microscopy. Samples of vaginal fluid were collected from 7
      normally cycling and healthy cows, 3 to 4 years of age, in oestrus. Evaluation of
      the patterns of crystallization was used as a previous assessment of the quality
      of the samples. SEM images revealed a structure made up of non-oriented filaments
      constituting a network with a three-dimensional arrangement. These filaments were
      of different diameters and ranged between 50 and 400 nm. Mesh size, defined as
      the minimum distance measurement between strands, ranged between 2 to 8 microns.

PMID- 9270347
TI  - Food-associated drinking in pygmy goats: importance of histamine receptors.
AB  - The combined effect of the histamine receptor antagonists Dexbrompheniramine
      (DXB: H1-receptor antagonist) and Cimetidine (C: H2-receptor antagonist) on food
      and water intake was investigated in pygmy goats. DXB (1 mg/kg BW0.75) and C (16
      mg/kg BW0.75) were injected together intraperitoneally (i.p.). Cumulative food
      and water intake, as well as meal and draft pattern, were recorded. DXB and C
      significantly reduced cumulative water intake, whereas cumulative food intake did
      not change. Water to food ratio was also significantly diminished. Draft
      frequency and the percentage of drafts associated with meals were significantly
      reduced during the 6 h post injection, while meal frequency and meal size did not
      change during this period. The results show that blockade of the H1- and H2
      histamine receptors attenuates the association between water and food intake in
      pygmy goats. Therefore, mechanisms responsible for meal-associated drinking seem
      to depend upon activation of histamine receptors.

PMID- 9270348
TI  - Molecular epidemiology of animal virus diseases.
AB  - In this review the application of methods of molecular epidemiology, particularly
      the combined approach of amplifying defined fragments of viral genomes using the
      polymerase chain reaction and subsequent nucleotide sequencing analysis, is
      described. Emphasis is put on examples of a few important diseases (e.g. those
      caused by morbilliviruses, rhabdoviruses, pestiviruses and aphthoviruses) to
      demonstrate the impact of this methodology. Molecular epidemiology is already an
      important and very sensitive tool to study the evolution of viruses at a level
      superior to previous methodologies and providing a better understanding of
      epidemiological relationships.

PMID- 9270349
TI  - Detection and characterization of enterohaemorrhagic Escherichia coli in
      slaughtered cattle.
AB  - Fecal samples from slaughtered cattle were studied for enterohaemorrhagic
      Escherichia coli (EHEC) by DNA hybridization with biotin-labelled DNA probes
      specific for the EHEC virulence plasmid, Shiga-like toxin I (SLT I), Shiga-like
      toxin II (SLT II) and eae gene. Among 136 animals analysed, 47 (34.5%) were found
      to carry EHEC. The cytotoxic genotypes observed for EHEC strains were: 60.4% SLT
      I, 12.5% SLT II and 10.4% SLT I + SLT II; 16.7% resulted SLT I and SLT II
      negative. A total of 14 out of 48EHEC strains (29.2%) hybridized with a fimbrial
      probe and 14 of 48 strains with an sas probe. An important number of strains (18
      out of 48) belonged to serogroups O157, O26 and O111, serogroups also commonly
      isolated from haemolytic uremic syndrome cases in Chile. While EHEC isolates from
      the same animal were usually of the same serogroup, one animal was found to carry
      two EHEC strains of different serogroups. A total of 50% of EHEC strains were
      sorbitol negative, irrespective of the O serogroup or EHEC genotypic profile.
      Results obtained in this study strongly suggest that cattle in Chile are a
      reservoir of EHEC associated with disease in humans.

PMID- 9270350
TI  - Comparative study of the pathogenic properties of a Belgian and a Greek
      encephalomyocarditis virus (EMCV) isolate for sows in gestation.
AB  - Thirteen conventional sows were inoculated between 61 and 92 days of gestation
      with a Belgium or a Greek EMCV isolate to investigate the difference in
      pathogenicity of both strains for sows in gestation. The Belgian EMCV strain was
      isolated from the offspring of a sow with productive failure and without
      myocardial lesions. The Greek strain was isolated from a 3-month-old pig with
      prominent myocardial lesions. The present study demonstrates a transplacental
      virus transmission with fetal death following an infection of the sows in
      gestation with both isolates. The fetal pathogenicity was more severe with the
      Greek strain than with the Belgian isolate. No myocardial lesions were noticed.

PMID- 9270351
TI  - Studies on the rod-coccus life cycle of Rhodococcus equi.
AB  - In the present study all 19 Rhodococcus equi cultures isolated from horses and 19
      of 22 R. equi cultures isolated from human patients displayed a rod-coccus life
      cycle after cultivation under defined growth conditions. A bacillary growth could
      be observed after cultivation of the bacteria in fluid media for 4 h at 37
      degrees C, a coccoid morphology after cultivation of the bacteria for 24 h either
      on sheep blood agar plates or in fluid media. The different morphological
      features did not significantly influence the typability of the bacteria or the
      expression of surface proteins including 15-17 kDa virulence proteins. Studies on
      further surface characteristics revealed a relation between haemagglutinating
      properties, the surface hydrophobicity and adherence properties of the bacteria
      to HeLa cells. These properties seemed to be influenced by the cultivation
      conditions but not by the different morphological forms of the bacteria. A
      haemagglutination reaction, a hydrophobic surface and an enhanced adherence to
      HeLa cells could be observed with coccoid bacteria after cultivation in fluid
      media for 24 h at 37 degrees C but not with coccoid bacteria harvested from sheep
      blood agar plates or with bacillary bacteria after 4 h growth in fluid media.
      This difference might possibly be caused by the degree of encapsulation of the
      bacteria after various cultivation conditions and a subsequent masking effect of
      the hydrophilic polysaccharide capsule of R. equi.

PMID- 9270352
TI  - Eperythrozoon ovis infection in a commercial flock of sheep.
AB  - A flock of sheep consisting of 60-70 winterfed ewes was examined. Blood was
      collected from approximately 30% of the sheep four times from 1991 to 1995.
      Eperythrozoon ovis (Ep. ovis) organisms were not detected in blood smears stained
      with Wright's stain in 1991 and 1993. In 1995, examination of blood smears
      stained with acridine orange revealed Ep. ovis organisms in 11 of 26 sheep,
      whereas examination of smears stained with Wright's stain revealed organisms in
      only one ewe with a high degree of infection. The prevalence of antibodies
      detected by IFAT varied from 58-100%. The antibody titres varied from 1:20 to
      1:12,000. This investigation indicates that Ep. ovis infection once present in a
      flock of sheep may spread easily among the sheep, and that the infection seems to
      persist within the flock.

PMID- 9270353
TI  - Atypical strains of verocytotoxin-producing Escherichia coli O157 in beef cattle
      at slaughter in Veneto region, Italy.
AB  - Cattle arriving for slaughter at abattoirs in the Veneto region of N. Italy were
      examined for intestinal carriage of Escherichia coli O157. Rectal swabs were
      cultured in modified buffered peptone water and E. coli O157 was concentrated by
      an immunomagnetic separation technique; the magnetic beads were cultured onto
      cefixime tellurite sorbitol MacConkey agar. Sorbitol non-fermenting E. coli O157
      was isolated from 15 (3.6%) of 419 feedlot cattle but not from 437 veal calves or
      65 culled cows. All strains of E. coli O157 hybridized with DNA probes specific
      for the VT1 or VT2 genes, but two strains did not produce toxin detectable by
      Vero cell assay. Six different plasmid profiles were observed with all strains
      harbouring the large 93 kb plasmid characteristic of VTEC. Six strains produced
      urease but otherwise strains were biochemically typical of E. coli O157. One
      strain was resistant to streptomycin, tetracycline and sulphonamides but the
      remainder were sensitive to all antimicrobials tested. This is the first
      description of the isolation of verocytotoxin-producing E. coli O157 from cattle
      in Italy. As the contamination of bovine carcasses with E. coli O157 during
      slaughter and processing has been demonstrated, the risk of transmission of this
      organism from beef cattle to the human population in the Veneto region, through
      foods of bovine origin or by other routes, should not be overlooked.

PMID- 9270354
TI  - Prevalence of antibodies to Eperythrozoon ovis in Norwegian sheep.

PMID- 9270355
TI  - Identification and characterization of staphylococci isolated from cutaneous
      lesions of goats.
AB  - Staphylococci from skin lesions of goats in Assam, India, were found to belong
      predominantly to the potentially dermatopathogenic species Staphylococcus aureus
      and Staphylococcus byicus. These species have not been described as components of
      the normal flora of the hairy skin of goats.

PMID- 9270356
TI  - Natural cilia-associated respiratory bacillus infection in rabbits used for
      elaboration of hyperimmune serum against Mycoplasma sp.
AB  - Cilia-associated respiratory (CAR) bacillus was identified in lung lesions of
      rabbits used for elaboration of hyperimmune serum against Mycoplasma mycoides
      ssp. capri (Mmc). Numerous Warthin Starry (WS) positive filamentous bacteria
      aligned perpendicularly to the surface of bronchial epithelial lining were
      observed. Immunoperoxidase staining of these bacteria was detected using a serum
      anti-rabbit CAR bacillus. Ultrastructural morphology corresponds to that of CAR
      bacilli previously reported in rabbits. The desirability of monitoring laboratory
      rabbits for CAR bacillus infection as part of the health programme is reinforced,
      especially in rabbits used for raising sera against respiratory pathogens of
      animal species in which CAR bacillus infection has been described. This is the
      first report of natural CAR bacillus infection in rabbits in Europe.

PMID- 9270357
TI  - Correspondence in pictorial space.
AB  - We have investigated psychophysically determined image correspondences between
      pairs of photographs of a single three-dimensional (3-D) object in various poses.
      These correspondences were obtained by presenting the pictures simultaneously,
      side by side, and letting the subject match a marker in one picture with a marker
      (under manual control) in the other picture. Between poses, the object was
      rotated about a fixed vertical axis; thus, the shifts of the veridical
      correspondences (with respect to the surface of the object) were very nearly
      horizontal. In fact, the subjects produced appreciable scatter in both horizontal
      and vertical directions. The scatter in repeated sessions and between data
      depends on the local (landmarks) and global (interpolation) structure of the
      pictures. Since the object was fairly smooth (white semigloss finish) and
      nontextured, the only way to establish the correspondence is by way of the
      "pictorial relief." The relief is some largely unknown function of the image
      structure and the observer. Apparently, more immediate entities (e.g., the
      shading or the contour) cannot be used as such, since they vary with the pose. We
      compare these data with results obtained with a surface attitude probe on a
      single picture. We studied various measures of consistency both within a single
      method and between methods. We found that subjects were confident in establishing
      correspondences, but results scattered appreciably in a way that depended on both
      global and local image structure. Correspondence results for various pose angles
      were mutually very consistent, but only to a minor extent with results of
      attitude measurements. The main finding was that subjects could establish
      correspondence on the basis of their 3-D interpretation (pictorial relief), even
      if the 2-D graytone distributions are quite different.

PMID- 9270358
TI  - The visual contour in depth.
AB  - We asked subjects to match points on the surface of a smooth three-dimensional (3
      D) shape with points on the surface of another object that was geometrically
      identical to the first object but was placed in a different pose, was differently
      textured, and was differently shaded. In all cases, the fiducial point was on the
      rim of one of the objects (i.e., the boundary of the visible region of the
      surface), whereas the matching point was well within the silhouette of the other
      object. This allowed us to draw (preliminary) conclusions concerning the way
      monocular human observers are able to handle the neighborhood of the rim, where
      the local slant assumes arbitrarily high values. All experiments were done in
      real space with real objects (no computer-simulated scenes), the points being
      indicated with laser beam illumination. The subject was given control over the
      direction of the laser beams and was thus able to perform the task by adjustment
      from the vantage position. We studied both consistency (whether the subject's
      judgments were invariant against changes of relative pose) and veridicality
      (whether the depth of the visual contour as calculated from the settings agreed
      with the true distance as measured by mechanical means). Subjects caught much of
      the 3-D structure of the contour but did deviate appreciably and apparently
      idiosyncratically from the true geometry.

PMID- 9270359
TI  - Perceiving the sex and identity of a talker without natural vocal timbre.
AB  - The personal attributes of a talker perceived via acoustic properties of speech
      are commonly considered to be an extralinguistic message of an utterance.
      Accordingly, accounts of the perception of talker attributes have emphasized a
      causal role of aspects of the fundamental frequency and coarse-grain acoustic
      spectra distinct from the detailed acoustic correlates of phonemes. In testing
      this view, in four experiments, we estimated the ability of listeners to
      ascertain the sex or the identity of 5 male and 5 female talkers from sinusoidal
      replicas of natural utterances, which lack fundamental frequency and natural
      vocal spectra. Given such radically reduced signals, listeners appeared to
      identify a talker's sex according to the central spectral tendencies of the
      sinusoidal constituents. Under acoustic conditions that prevented listeners from
      determining the sex of a talker, individual identification from sinewave signals
      was often successful. These results reveal that the perception of a talker's sex
      and identity are not contingent and that fine-grain aspects of a talker's
      phonetic production can elicit individual identification under conditions that
      block the perception of voice quality.

PMID- 9270360
TI  - Individual differences in the vibrotactile perception of a "simple" pattern set.
AB  - Discriminative capacities for vibrotactile spatiotemporal patterns were examined
      in 62 college students with three tasks: identification, masking, and
      discrimination of the letters "X" and "O" presented tactually on the Optacon, a
      reading machine for blind persons. Individual differences in performance and
      interrelations among scores within and across paradigms were explored. In
      identification, most persons quickly achieved consistently better than 90%
      performance, but others failed to identify the patterns above 80%, even after
      prolonged training. The same performance variance was found when the task was
      repeated by 23 Naval student pilots. Masking and discrimination measured
      susceptibility to interference when patterns followed one another closely in
      time. The resulting functions were typical, with poorest performance at short
      stimulus onset asynchronies. Again, a wide range of performance was seen.
      Individual performance, however, appeared to be consistent across tasks,
      suggesting that abilities in a variety of pattern-perception tasks might be
      predictable.

PMID- 9270361
TI  - Evaluation of maximum-likelihood estimators in nonintensive auditory
      psychophysics.
AB  - This is a brief report on the use of maximum-likelihood (ML) estimators in
      auditory psychophysics. Slope parameters of psychometric functions are
      characterized for three nonintensive auditory tasks: forced-choice discrimination
      of interaural time differences (delta ITD), frequency (delta f), and duration
      (delta t). Using these slope estimates, the ML method is implemented and
      threshold estimates are obtained for the three tasks and compared with previously
      published data. delta ITD thresholds were additionally measured for human
      observers by means of two other psychophysical procedures: the constant-stimuli
      (CS) and the 2-down 1-up methods (Wetherill & Levitt, 1965). Standard errors were
      smallest for the ML method. Finally, simulations showed ML estimates to be more
      efficient than the CS and k-down 1-up procedures for k = 2 to 5. For up-down
      procedures, efficiency was highest for k values of 3 and 4. The entropy (Shannon,
      1949) of ML estimates was the smallest of the simulated procedures, but poorer
      than ideal by 0.5 bits.

PMID- 9270362
TI  - The representational basis of syllable categories.
AB  - Two hypotheses concerning the relation between phoneme and syllable categories
      are contrasted. The phonological hypothesis holds that phoneme categories are
      perceptually basic, whereas syllable categories are abstract and specify the
      phonological rules operating on phoneme categories. The integrative routine
      hypothesis suggests that whereas phoneme categories are basic, syllable
      categories are not entirely abstract but are represented at least partially on
      the basis of higher order perceptual information, specifying the dynamics of
      coarticulating phoneme categories. Three experiments used a primed naming task in
      which subjects had to name the entire syllable (consonant-vowel and vowel
      consonant; Experiment 1), the syllable-initial phoneme category (Experiment 2),
      or the syllable-final phoneme category (Experiment 3). The results supported the
      integrative routine hypothesis.

PMID- 9270363
TI  - The relationship between central cues and peripheral cues in covert visual
      orientation.
AB  - Four experiments were conducted to compare valid and invalid cue conditions for
      peripheral and central cues. Experiments 1, 3, and 4 used reaction time (RT) as
      the dependent variable. Experiment 2 used a threshold measure. Peripheral and
      central cues were presented on each trial. The peripheral cue was uninformative
      in all experiments. The central cue was informative in Experiments 1 and 2, where
      it predicted stimulus side on 70% of the trials. Experiment 3 included 50% and
      100% central-cue prediction conditions as well as the 70% treatment. Experiment 4
      included 60%, 75%, and 90% central-cue prediction conditions. The effects of the
      central and peripheral cues were independent and additive in all four
      experiments, indicating that: (1) both cue types can act simultaneously, and that
      the relationship between them is additive under the conditions used in these
      experiments, (2) informativeness is not a necessary condition for attentional
      effects with peripheral cues, and (3) covert visual orientation influences
      sensory thresholds and RT in similar ways. The results of Experiments 3 and 4
      demonstrated that the facilitation associated with peripheral cues was
      insensitive to manipulations which demonstrate that subjects use the
      informational value of the central cue to direct voluntary attention. The results
      are discussed with reference to two issues; first, the proposition that central
      and peripheral cues exert their influence on performance in independent
      information-processing stages, following the additive factor method, and, second,
      the problems raised for additive factors method when cues elicit both an
      "explicit" response-regarding the presence or absence of a specified letter-and
      an "implicit response"-involving the planning and possible execution of eye and
      hand movements.

PMID- 9270364
TI  - Sequence effects in hedonic judgments of taste stimuli.
AB  - Sequential dependencies in taste research may be different from those obtained in
      other modalities, due to the long interstimulus intervals and the intermediate
      rinses. In two experiments, subjects judged the pleasantness of 50 aqueous
      solutions on 150-mm line scales. During data analyses pseudo-sequence effects
      arose, because data were aggregated over individuals and because the first trials
      of the experimental sessions deviated from the rest. After correcting for the
      pseudo-sequence effects, robust regression analyses revealed small but
      significant sequential dependencies. The current response deviation was
      positively related to previous response deviations and negatively related to
      previous subjective, internal representations.

PMID- 9270365
TI  - Judgments of relative time-to-contact of more than two approaching objects:
      toward a method.
AB  - Observers reported which of as many as eight computer-generated approaching
      objects would "hit" them first. Accuracy was above chance probability except when
      two-object displays contained pictorial relative size information that
      contradicted relative time-to-contact (TTC) information. Mean d' and response
      time was greater, but mean efficiency (Barlow, 1978) was smaller with eight
      objects than with two. Performance was less effective when global expansion
      contradicted TTC information than when local expansion contradicted TTC. Results
      suggest that observers can judge relative TTC with as many as eight objects when
      certain sources of information are consistent with TTC and that observers rely on
      information other than, or in conjunction with, optical TTC. Also, the sources of
      visual information that affect performance may vary with set size, and
      identification (but not detection) judgments may be constrained by limited
      capacity processing.

PMID- 9270366
TI  - Unification of psychophysical phenomena: the complete form of Fechner's law.
AB  - Many of the laws and empirical observations of fundamental psychophysics can be
      unified with a single equation, which has been called the complete form of
      Fechner's law. It can be shown that this law embraces both of the commonly used
      forms: Stevens's and Fechner's laws. It assumes one or the other form with
      appropriate values of the parameters. However, the complete equation confers an
      advantage beyond simply containing the classical laws. It offers greater
      flexibility in the representation of experimental data. It is shown that
      psychophysical phenomena may be represented by any number of triplets of
      quantities: subjective magnitude of stimulus, subjective just noticeable
      difference (jnd), and differential threshold. Each of the preceding quantities
      are functions of the physical magnitude of the stimulus. The investigator has the
      license to choose two of these quantities in the form he or she thinks is best;
      the third quantity is determined by the choice of the first two. Thus, for
      example, different forms of the law of sensation and different forms of the
      mathematical function for differential threshold may coexist with equal validity.

PMID- 9270367
TI  - Local and global orientation in visual search.
AB  - Six experiments investigated the role of global (shape) and local (contour)
      orientation in visual search for an orientation target. Experiment 1 demonstrated
      that search for a conjunction of local contours with a distinct global
      orientation was less efficient than search for a target featurally distinct in
      terms of both global and local contour orientation. However, Experiments 2 and 4
      demonstrated that the presence of a unique line contour was neither sufficient
      nor necessary to allow efficient search. Experiment 5 found that search for a
      local orientation difference was strongly impeded by irrelevant variation in
      global orientation, arguing for a preeminent role for global orientation.
      Finally, Experiment 6 demonstrated that the orientation search asymmetry holds
      for the global orientation of stimuli. Taken together, the results are consistent
      with visual search processes guided predominantly by a representation of global
      orientation.

PMID- 9270368
TI  - Inhibition of return in location- and identity-based choice decision tasks.
AB  - Three experiments were conducted to determine whether inhibition of return can be
      best characterized as an attentional or a motor phenomenon. In the first
      experiment, subjects made choice keypress responses to the location of a target
      (left or right) or the identity of the target (X or +) by pressing a left or
      right response key. In the second experiment, the display was rotated 90 degrees
      so that there was no direct spatial mapping between the vertically aligned
      stimulus display and the horizontally aligned response keys. In both experiments,
      inhibition of return was observed for location-based and identity-based choice
      responses, although more inhibition was seen in the identity-based responses. The
      results of the third experiment suggested that this larger inhibitory effect may
      be specific to the covert orienting of reflexive attention in response to the
      sudden appearance of a single peripheral stimulus in the identity tasks. Overall,
      the results are consistent with the attentional, not the motor, explanation of
      inhibition of return.

PMID- 9270369
TI  - The influence of affective factors on time perception.
AB  - Several studies have suggested that both affective valence and arousal affect the
      perception of time. However, in previous experiments, the two affective
      dimensions have not been systematically controlled. In this study, standardized
      photographic slides rated for emotional valence and arousal were projected to two
      groups of subjects for 2, 4, and 6 sec. One group of subjects estimated the
      projection duration on an analog scale, whereas the second group of subjects
      reproduced the intervals by pushing a button. Heart rate and skin conductance
      responses were also recorded during stimulus presentation as indices of attention
      and arousal. Time estimation results showed neither a main effect of valence nor
      a main effect of arousal. A highly significant valence x arousal interaction
      affected duration judgments. For low-arousal stimuli, the duration of negative
      slides was judged relatively shorter than the duration of positive slides. Fog
      high-arousal stimuli, the duration of negative slides was judged longer than the
      duration of positive slides. The same interaction pattern was observed across
      judgment modalities. These results are interpreted in terms of a model of action
      tendency, in which the level of arousal controls two different motivational
      mechanisms, one emotional and the other attentional.

PMID- 9270370
TI  - Taxol biosynthesis: an update.
AB  - The novel diterpenoid taxol (paclitaxel) is now well-established as a potent
      chemotherapeutic agent. Total synthesis of the drug is not commercially feasible
      and, in the foreseeable future, the supply of taxol and its synthetically useful
      progenitors must rely on biological methods of production. The first three steps
      of taxol biosynthesis have been defined and the responsible enzymes described.
      These are the cyclization of the universal diterpenoid precursor geranylgeranyl
      diphosphate to taxa-4(5),11(12)-diene, the cytochrome P450-catalyzed
      hydroxylation of this olefin to taxa-4(20), 11(12)-dien-5 alpha-ol, and the
      acetyl CoA-dependent conversion of the alcohol to the corresponding acetate
      ester. Demonstration of these early steps of taxol biosynthesis suggests that the
      complete pathway can be defined by a systematic, stepwise approach at the cell
      free enzyme level. When combined with in vivo studies to determine contribution
      to pathway flux, slow steps can be targeted for gene isolation and subsequent
      overexpression in Taxus to improve the yield of taxol and related compounds.

PMID- 9270371
TI  - Piperbetol, methylpiperbetol, piperol A and piperol B: a new series of highly
      specific PAF receptor antagonists from Piper betle.
AB  - Piperbetol, methylpiperbetol, piperol A, and piperol B, isolated from Piper
      betle, selectively inhibited the washed rabbit platelet aggregation induced by
      platelet activating factor (PAF) in a concentration-dependent manner. The IC50
      values of piperbetol, methylpiperbetol, piperol A, piperol B, and ginkgolide B
      were about 18.2, 10.6, 114.2, 11.8, and 4.8 mumol/l, respectively. The inhibitory
      potency of ginkgolide B was about 2.8, 1.2, 22.8, and 1.4 times higher than those
      of piperbetol, methylpiperbetol, piperol A, and piperol B. The concentration
      response curve of PAF-induced platelet aggregation was shifted to the right by 50
      mumol/l of piperbetol, methylpiperbetol, piperol A, piperol B, and ginkgolide B.
      The EC50 of PAF was increased by these compounds from 1.5 nmol/l to 14.3, 23.1,
      2.4, 20.6, and 47.2 nmol/l, respectively. The compounds also inhibited the
      binding of [3H]-PAF to washed rabbit platelets with IC50 values of 8.7, 5.3, 88,
      6.2, and 1.8 mumol/l. Correlating with the inhibitory potency for platelet
      aggregation, the inhibitory potency of ginkgolide B for binding of PAF was about
      3.8, 1.9, 48, and 2.4 times higher than those of piperbetol, methylpiperbetol,
      piperol A, and piperol B. However, the aggregation of washed rabbit platelets
      induced by threshold ADP and arachidonic acid were unaffected by piperbetol,
      methylpiperbetol, piperol A, and piperol B. Furthermore, piperbetol,
      methylpiperbetol, piperol A, and piperol B had no effects on the cAMP contents in
      rest washed rabbit platelets. In conclusion, these data indicate that piperbetol,
      methylpiperbetol, piperol A, and piperol B are effective PAF receptor antagonists
      in vitro.

PMID- 9270372
TI  - Relaxation of evoked contractile activity of isolated guinea-pig ileum by (+/-)
      kavain.
AB  - Kava pyrones are the pharmacologically active compounds of Piper methysticum
      Forst. In the present study, the effect of the synthetic kava pyrone (+/-)-kavain
      was investigated on evoked contractile activity of isolated guinea-pig ileum. (+/
      )-Kavain (1 microM-1 mM) dose-dependently reduced contractions of ileum evoked by
      carbachol (10 microM), by BAY K 8644 (0.3 microM), or by substance P (0.05
      microM). (+/-)-Kavain also inhibited the contractile responses induced by raising
      the extracellular K+ concentration from 4 to 20 mM and by blocking the K+ channel
      by barium chloride (1 mM) or 4-aminopyridine (0.3 mM). After pre-incubation with
      1 microM nifedipine, carbachol (1 microM) evoked 18.2 +/- 14.3% of contraction at
      control (i.e. prior pre-incubation with nifedipine). This remaining response was
      completely abolished by high concentrations of (+/-)-kavain (400 microM). After
      treatment of the longitudinal ileum strips with pertussis toxin (PTX), carbachol
      (1 microM) evoked 27.0 +/- 6.2% of the control response in untreated ileum. These
      contractions were also blocked by (+/-)-kavain (400 microM). However, (+/-)
      kavain had no effect on the caffeine-induced (20 mM) contractions of ileum
      strips, which were permeabilized with digitonin or beta-escin. Moreover, it
      failed to affect Ca(2+)-evoked contractions of skinned muscles. These results
      suggest that the kava pyrone (+/-)-kavain may act in a non-specific musculotropic
      way on the smooth muscle membrane.

PMID- 9270373
TI  - The inhibiting effects of Urtica dioica root extracts on experimentally induced
      prostatic hyperplasia in the mouse.
AB  - Extracts of stinging nettle roots (Urtica dioica L. Urticaceae) are used in the
      treatment of benign prostatic hyperplasia (BPH). We established a BPH-model by
      directly implanting an urogenital sinus (UGS) into the ventral prostate gland of
      an adult mouse. Five differently prepared stinging nettle root extracts were
      tested in this model. The 20% methanolic extract was the most effective with a
      51.4% inhibition of induced growth.

PMID- 9270374
TI  - Protective effect of boldine in experimental colitis.
AB  - The cytoprotective and anti-inflammatory effects of boldine in an experimental
      model of acute colitis are reported. The administration of boldine to animals
      with colitis induced by the intrarectal administration of acetic acid, was found
      to protect against colonic damage as expressed by major reductions in the extent
      of cell death, tissue disorganization, and edema. Boldine also reduced the
      colonic neutrophil infiltration, as measured by the myeloperoxidase activity, but
      it did not significantly affect tissue lipoperoxides. Boldine was found to
      preserve the colonic fluid transport, a function otherwise markedly affected in
      the tissue of acid-treated animals. Results presented here provide experimental
      evidence supporting new cytoprotective and anti-inflammatory properties of
      boldine.

PMID- 9270375
TI  - Isolation and immunomodulatory effect of flavonol glycosides from Epimedium
      hunanense.
AB  - The ethyl acetate and n-butanol fractions from aerial parts of E. hunanense were
      initially screened to find active fractions with immunomodulatory activity. Nine
      compounds, tricin (1), luteolin (2), thalictoside (3), icariin I (4), baohuoside
      I (5), quercitrin (6), icariin (7), epimedin C (8), and B (9) were isolated from
      this species for the first time, and 3 was isolated for the first time from
      flavonoid extracts of the genus. Their structures were established by chemical
      and spectroscopic methods. The immunomodulatory effects of the n-butanol fraction
      and epimedin C isolated from the fraction were investigated. Hydrocortisone
      acetate (HCA) was used as an immunosuppressant to inhibit the immune response of
      mice. The n-butanol fraction and epimedin C significantly enhanced the response
      of spleen antibody-forming cells (SAFC) to near normal in the mice treated with
      HCA. They also significantly enhanced lymphocyte proliferation and caused a
      significant recovery of interleukin-2 (IL-2) production in the mice inhibited
      with HCA. In conclusion, they are active principles with immunoenhancing effects.

PMID- 9270376
TI  - Antidiabetic effect of seishin-kanro-to in KK-Ay mice.
AB  - The hypoglycemic effect of Seishin-kanro-to (SK) was investigated in KK-Ay mice,
      one of the non-insulin dependent diabetic mellitus types. SK (1700 mg/kg) reduced
      the blood glucose of KK-Ay mice from 557 +/- 17 to 383 +/- 36 mg/100 ml 7 hours
      after single oral administration (P < 0.001). SK also decreased the blood glucose
      and improved glucose tolerance 5 weeks after repeated administration in KK-Ay
      mice. These results support, therefore, the use of SK in patients with diabetes
      and confirm its role as a traditional medicine. In addition, the active plants of
      SK were identified as the rhizome of Anemarrhena asphodeloides Bunge and the
      radix of Rehmannia glutinosa Liboschitz.

PMID- 9270377
TI  - Antihyperglycemic effects of paeoniflorin and 8-debenzoylpaeoniflorin, glucosides
      from the root of Paeonia lactiflora.
AB  - Paeoniflorin and 8-debenzoylpaeoniflorin were isolated from the dried root of
      Paeonia lactiflora Pall. (Ranunculaceae). They produced a significant blood sugar
      lowering effect in streptozotocin-treated rats and had a maximum effect at 25 min
      after treatment. This hypoglycemic action was also observed in normoglycemic rats
      only at 1 mg/kg. The antihyperglycemic activity of 8-debenzoylpaeoniflorin seems
      lower than that of paeoniflorin. Plasma insulin was not changed in paeoniflorin
      treated normoglycemic rats indicating an insulin-independent action. Also, this
      glucoside reduced the elevation of blood sugar in glucose challenged rats.
      Increase of glucose utilization by paeoniflorin can thus be considered. There are
      no previous data showing the hypoglycemic activity of paeoniflorin and/or 8
      debenzoylpaeoniflorin in rats.

PMID- 9270378
TI  - Isoquinoline alkaloids from Argemone mexicana reduce morphine withdrawal in
      guinea pig isolated ileum.
AB  - The present study examined the effect of the MeOH extract, partially purified
      fraction (IV), and pure compounds from Argemone mexicana L. (Papaveraceae) on the
      morphine withdrawal in guinea pig isolated ileum. The MeOH extract, the partially
      purified fraction (IV), and the pure compounds isolated from A. mexicana
      significantly and in a concentration-dependent manner reduced the morphine
      withdrawal. Since the pure compounds were identified as protopine and
      allocryptopine, the observed effects could be related to these compounds. The
      results of the present study suggest that isoquinoline alkaloids may be potential
      agents in the treatment of drug abuse.

PMID- 9270379
TI  - In vitro cytotoxicity of tanshinones from Salvia miltiorrhiza.
AB  - The cytotoxicity-guided fractionation of the roots of Salvia miltiorrhiza B.
      (Labiatae) extracts led to the isolation of eighteen active principles 1-18,
      responsible for the cytotoxicity against five cultured human tumor cell lines,
      i.e., A549 (non-small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498
      (central nerve system) and HCT-15 (colon), using the SRB (sulfrhodamine-B) method
      in vitro. All active compounds 1-18 including two novel components 5 and 11 were
      comprised of tanshinone pigments, unusual diterpenes exclusively found in this
      species. The proliferation of each examined tumor cell line was significantly
      inhibited (IC50 values ranged from 0.2 to 8.1 micrograms/ml) during the
      continuous exposure of tumor cells to 1-18 for 48 hours, respectively.

PMID- 9270380
TI  - Decursinol angelate: a cytotoxic and protein kinase C activating agent from the
      root of Angelica gigas.
AB  - A cytotoxic compound was purified from the root of Angelica gigas Nakai by normal
      phase HPLC. As a result of the structure analysis by mass, IR, 1H-NMR, and 13C
      NMR spectrometry, the compound was identified as decursinol angelate, a
      structural isomer of decursin, and characterized originally from Sesei
      grandivittatum. Decursinol angelate showed in vitro cytotoxicity and protein
      kinase C activating activities like decursin.

PMID- 9270381
TI  - Inhibition of tyrosine hydroxylase by bulbocapnine.
AB  - The inhibitory effects of bulbocapnine, an aporphine isoquinoline alkaloid, on
      bovine adrenal tyrosine hydroxylase (TH) were investigated. Bulbocapnine had an
      inhibitory effect on the enzyme (43.6% inhibition at concentration of 200
      microM). Bulbocapnine exhibited uncompetitive inhibition on bovine adrenal TH
      with a substrate L-tyrosine. The Ki value was found to be 0.20 mM.

PMID- 9270382
TI  - Cytotoxic constituents from the stems of Diospyros maritima.
AB  - One novel coumaric acid ester of lupeol, dioslupecin A (1), three
      naphthoquinones, 8'-hydroxyisodiospyrin (2), isodiospyrin (3), and plumbagin (4),
      three triterpenes, lupeol, lupenone and taraxerone, and four sterols, beta
      sitosterol, stigmasterol, stigmast-4-en-3-one and ergosta-4,6,8(14),22-tetraen-3
      one were isolated from the n-hexane extract of the stems of Diospyros maritima
      Blume. The structural determination of 1 was based on 1D and 2D NMR spectra
      (including 1H-1H COSY, 1H-13C COSY, and HMBC). All compounds were evaluated for
      in vitro cytotoxicity in 4 cancer cell lines. Compound 2 showed similar
      cytotoxicity against hepatoma (HEPA-3B, ED50 = 1.72 micrograms/ml), nasopharynx
      carcinoma (KB, ED50 = 1.85 micrograms/ml), colon carcinoma (COLO-205, ED50 = 2.24
      micrograms/ml) and cervical carcinoma (HELA, ED50 = 1.92 micrograms/ml).
      Compounds 3 and 4 exhibited strong cytotoxicity against HEPA-3B, KB, COLO-205 and
      HELA (ED50 = 0.25, 1.81, 0.13 and 0.27 micrograms/ml for 3; ED50 = 0.87, 3.27,
      0.56 and 0.35 micrograms/ml for 4, respectively.

PMID- 9270383
TI  - Antimitotic and cytotoxic constituents of Myodocarpus gracilis.

PMID- 9270384
TI  - Studies on the anti-inflammatory activity of rhizomes of Nelumbo nucifera.
AB  - The anti-inflammatory activity of the methanol extract of Nelumbo nucifera
      rhizome as well as of betulinic acid, a steroidal triterpenoid isolated from it,
      were evaluated on carrageenin and serotonin induced rat paw edema. Methanol
      extract at doses of 200 and 400 mg/kg and betulinic acid at doses of 50 mg/kg and
      100 mg/kg p.o., showed significant anti-inflammatory activity in both the models
      of inflammation in rats. The effects produced were comparable to that of
      phenylbutazone and dexamethasone, two prototype anti-inflammatory drugs.

PMID- 9270385
TI  - Erythroxan diterpenes from Fagonia glutinosa.
AB  - Further investigation of the ether extract of the aerial parts of Fagonia
      glutinosa utilizing the brine shrimp bioassay resulted in the isolation of two
      new cytotoxic erythroxan diterpenes: 1 alpha, 10 alpha-epoxy-2-oxofagonene (1)
      and 1 beta, 10 beta-epoxy-2-oxofagonene (2). In addition, two inactive
      diterpenes, 2-oxofagonene (3) and its previously reported isomer 2-oxo-5-epi
      fagonene (4), were also isolated.

PMID- 9270386
TI  - New spirostanol glycosides from Anemarrhena asphodeloides.
AB  - Two new spirostanol saponins, named anemarsaponin F (2b) and G (4b), along with
      six known spirostanol saponins were obtained from the rhizomes of Anemarrhena
      asphodeloides Bunge. On the basis of spectral analyses and chemical evidence, the
      structures of 2b and 4b were established as neogitogenin 3-O-beta-glucopyranosyl
      (1-->2) [beta-xylopyranosyl-(1-->3)]-beta-glucopyranosyl (1-->4)-beta
      galactopyranoside) and lilagenin 3-O-beta-glucopyranosyl-(1-->2)-[beta
      xylopyranosyl-(1-->3)]-beta- glucopyranosyl-(1-->4)-beta-galactopyranoside,
      respectively.

PMID- 9270387
TI  - Antiviral flavonoids from Alkanna orientalis.

PMID- 9270388
TI  - Cytotoxic components of Artemisia princeps.

PMID- 9270389
TI  - 1996 annual report of the American Association of Poison Control Centers Toxic
      Exposure Surveillance System.

PMID- 9270390
TI  - Fluoxetine-induced cardiotoxicity with response to bicarbonate therapy.
AB  - This report describes a patient with an acute intentional fluoxetine exposure who
      developed unique cardiovascular and neurovascular toxicity. The patient presented
      with lethargy and cardiac conduction delays (QRS 110 msec, QTc 458 msec) and
      developed a delayed seizure. On admission, therapy with intravenous sodium
      bicarbonate promptly narrowed the QRS to 90 msec. A comprehensive toxicology
      screen demonstrated only a serum fluoxetine concentration of 901 ng/mL
      (therapeutic range, 37-301), a serum norfluoxetine concentration of 451 ng/mL (29
      329) and a serum acetaminophen concentration of 174 mg/L. Tricyclic
      antidepresants were specifically noted to be absent. A self-limiting generalized
      seizure was witnessed 16 hours after ingestion. At this time the bicarbonate
      infusion had been ceased and the QRS interval was not prolonged. The patient
      improved over time and no other apparent causes for the observed clinical effects
      could be discovered. Emergency physicians need to be aware of the uncommon
      occurrence of fluoxetine-induced cardiotoxicity and the potential benefit of
      sodium bicarbonate therapy.

PMID- 9270391
TI  - Multiorgan system failure caused by valproic acid toxicity.
AB  - Valproic acid is an effective antiseizure medication that is also used for other
      indications such as migraine prophylaxis. It is known to sometimes cause hepatic
      injury, both a mild dose-related form and an idiosyncratic, fulminant, usually
      fatal type. A case is reported of multiorgan failure caused by valproic acid
      toxicity in an adult who survived. Such multisystem toxicity has not been
      previously reported.

PMID- 9270392
TI  - Thoracic aortic dissection secondary to crack cocaine ingestion.
AB  - Thoracic aortic dissection is a rare but recognized complication of crack cocaine
      inhalation. It is thought to be triggered in some cases by transient severe
      elevations in blood pressure, causing a shear effect on the thoracic aorta.
      Unrecognized, it can result in high morbidity and mortality. A case of an unusual
      presentation of thoracic aortic dissection following crack cocaine ingestion is
      reported.

PMID- 9270394
TI  - Cocaine-associated dystonic reaction.
AB  - Dystonic reactions are extrapyramidal motor dysfunctions that result from an
      insufficient activity of nigrostriatal dopamine and present clinically as spasms
      of the various muscle groups. Neuroleptic drugs are a known cause of dystonia and
      are the most frequently encountered trigger. Cocaine use has been associated with
      dystonias, though much less often. When reported in the setting of a dystonic
      reaction, cocaine has been described as a predisposing factor for the patient
      already using neuroleptic agents. Fewer reports of dystonia as a direct result of
      cocaine use, independent of neuroleptics, are found in the literature. The cases
      of two acute dystonic reactions secondary to cocaine use are presented, with a
      discussion of the pathophysiology and treatment alternatives.

PMID- 9270393
TI  - Cocaine-associated intestinal gangrene in a pregnant woman.
AB  - A 31-year-old pregnant woman who was an active cocaine abuser presented to our
      emergency department five times in 1 week for abdominal pain and vomiting. She
      continued to use cocaine regularly despite having abdominal pain. Her fifth
      admission was for seizures. There were no objective signs of peritoneal
      inflammation and the rectal guiac examination was repeatedly negative. The
      patient progressed to severe septic shock. Intraabdominal sepsis and/or bowel
      perforation was suspected. Exploratory laporatomy revealed gangrene and
      perforation of the small intestine and fecal peritonitis. She rapidly developed
      multiorgan failure and died. Gastrointestinal complications resulting from
      cocaine use are uncommon. Our case is unique in that the patient was pregnant,
      used cocaine by the intranasal route, and lacked objective signs of acute
      abdomen. Emergency physicians should be aware of the morbidity associated with
      the use of cocaine.

PMID- 9270395
TI  - American mistletoe exposures.
AB  - American mistletoe is generally considered to be extremely toxic. Although there
      are no data to support this contention, both the lay public and medical
      professionals often respond very aggressively after ingestion of any portion of
      this plant. To determine if American mistletoe is deserving of this reputation,
      the outcomes of 1,754 exposures to this plant were examined. All mistletoe data
      extracted from the American Association of Poison Control Centers national data
      collection system for the period of 1985 to 1992 were analyzed according to
      patient age, gastrointestinal decontamination therapy, patient outcome, and
      geographic region of the exposure. Pediatric exposures accounted for 92.1% of the
      cases, and 94.7% of the reported cases were accidental exposures. Of all cases,
      99.2% had an outcome associated with no morbidity, and there were no fatalities.
      Apparently, patient outcome was not influenced by the use of gastrointestinal
      decontamination techniques-96.2% of treated patients remained asymptomatic versus
      96.3% of patients who received no therapy. The accidental ingestion of American
      mistletoe is not associated with profound toxicity.

PMID- 9270396
TI  - Visual hallucinations in a toddler: accidental ingestion of a sympathomimetic
      over-the-counter nasal decongestant.
AB  - Hallucinations are uncommonly encountered in the young child. The differential
      diagnosis of such behavior includes a number of potentially serious syndromes
      such as central nervous system malignancy, encephalitis, temporal lobe epilepsy,
      closed head trauma with frontal lobe confusion, hypoglycemia, drug intoxications,
      and childhood psychiatric syndromes. Organic explanations are most often
      discovered and frequently involve toxicologic causes. A case is presented of a
      toddler with hallucinations caused by inappropriately high doses of
      pseudoephedrine.

PMID- 9270397
TI  - Unexpected nerve gas exposure in the city of Matsumoto: report of rescue activity
      in the first sarin gas terrorism.
AB  - This report describes the rescue activities and the exposure of rescue and
      hospital personnel from the first unexpected nerve gas terrorist attack using
      sarin (isopropyl methylphophonofluoridate) in the city of Matsumoto at midnight
      on June 27, 1994. The details of the emergency activities in the disaster were
      studied based on the records from emergency departments of the affiliated
      hospitals and records from the firehouse. About 600 people, including residents
      and rescue staff, were exposed to sarin gas. Fifty-eight residents were admitted
      to hospitals, and 7 died. Among 95 rescuers and the duty doctor from the doctor
      car, 8 had mild symptoms of poisoning. All the rescue activity took place without
      gas masks or decontamination procedures. In this case of unexpected mass exposure
      to sarin gas, the emergency rescue system for a large disaster in Matsumoto city,
      which had been established for a conflagration or a local earthquake, was
      effective.

PMID- 9270399
TI  - Exotic reptile bites.
AB  - Reptiles are a growing part of the exotic pet trade, and reptile bites have been
      considered innocuous in the emergency medicine literature. Two cases are reported
      of reptile bites, one from a green iguana and the other from a reticulated
      python. The treatment concerns associated with reptile bites are discussed.

PMID- 9270398
TI  - Anticholinergic poisoning in colicky infants treated with hyoscyamine sulfate.
AB  - Hyoscyamine, one of the principal alkaloid components of belladonna, is a potent
      anticholinergic agent. Because of its anticholinergic properties, hyoscyamine
      sulfate drops are often prescribed for the treatment of colic in infants.
      Anticholinergic poisoning in infants is rare. However, five cases are reported of
      infants with anticholinergic toxicity following the administration of hyoscyamine
      drops for the treatment of colic. Common presenting symptoms included
      irritability, tachycardia, and erythematous flushed skin. These cases emphasize
      the need for a heightened awareness by emergency physicians and pediatricians of
      possible anticholinergic toxicity caused by the use of hyoscyamine for infant
      colic.

PMID- 9270400
TI  - Unrecognized pregnancy in the overdosed or poisoned patient.
AB  - A 22-year-old woman was found in bed unresponsive and hypotensive after an
      apparent overdose. Subsequent workup in the emergency department identified a
      ruptured ectopic pregnancy and extensive hemoperitoneum. A significant delay
      occurred when emergency physicians excluded the possibility of pregnancy because
      of the patient's normal menstrual history. A qualitative serum or urine pregnancy
      test is recommended in all women of child-bearing age who present with poisoning
      or drug overdose.

PMID- 9270401
TI  - Torsades de pointes with terfenadine ingestion.
AB  - Torsades de pointes (TDP) is a ventricular tachycardia that can deteriorate into
      ventricular fibrillation. TDP has been associated with terfenadine use in cases
      of liver disease, electrolyte abnormalities, concomitant administration of drugs
      that inhibit cytochrome P-450, or deliberate overdose. This report describes the
      first case of TDP in a healthy patient taking the recommended therapeutic dosage
      of terfenadine.

PMID- 9270402
TI  - Cocaine balloon aspiration: successful removal with bronchoscopy.
AB  - Ingestion of balloons containing illicit substances along with the potential
      toxic sequelae associated with these ingestions have been described in the
      literature. This report describes the successful bronchoscopic retrieval of a
      cocaine balloon after aspiration. A 39-year-old man was witnessed swallowing
      several balloons that were thought to contain heroin. Shortly after ingestion,
      the patient became unconscious and required nasotracheal intubation. Before
      intubation, several balloons were removed from the oropharynx. Naloxone 4 mg was
      administered en route to the emergency department (ED). Following naloxone, the
      patient awoke and became agitated and combative. On arrival in the ED, midazolam,
      succinylcholine, and vecuronium were required to manage his combativeness. Vital
      signs were: heart rate, 130 beats/min; blood pressure, 128/86 mm Hg;
      respirations, 12 breaths/min; temperature, 96.5 degrees F. A balloon and balloon
      tip were removed during lavage. Whole bowel irrigation with a polyethylene glycol
      electrolyte solution was initiated. A right upper lobe infiltrate was identified
      on chest X-ray and aspiration of a balloon was suspected. At bronchoscopy, a
      small yellow, intact balloon visualized in the basilar segment of the right lower
      lobe was removed. Toxicologic analysis of the balloon contents found cocaine. The
      rest of the patient's hospital course was unremarkable and he was discharged 5
      days after admission. This case brings to light the potential concerns, such as
      respiratory compromise, associated with aspiration of small balloons in the body
      stuffer. Additionally, the potential for the development of toxicity if the
      balloon ruptures and toxin absorption occurs through through the lungs should be
      considered. Emergency physicians and toxicologists should be aware of this
      significant complication of packet ingestion in the body packer or stuffer and be
      prepared to intervene early during the course of the patient's treatment.

PMID- 9270403
TI  - Treatment of theophylline overdose.

PMID- 9270404
TI  - Apnea and oxyhemoglobin desaturation after intramuscular ketamine administration
      in a 2-year-old child.

PMID- 9270405
TI  - Garlic burns of the breast.

PMID- 9270406
TI  - Diphenhydramine-induced psychosis with therapeutic doses.

PMID- 9270407
TI  - Anthropometric measurements and vertebral deformities. European Vertebral
      Osteoporosis Study (EVOS) Group.
AB  - To investigate the association between anthropometric indices and
      morphometrically determined vertebral deformity, the authors carried out a cross
      sectional study using data from the European Vertebral Osteoporosis Study (EVOS),
      a population-based study of vertebral osteoporosis in 36 European centers from 19
      countries. A total of 16,047 EVOS subjects were included in this analysis, of
      whom 1,973 subjects (915 males, 1,058 females) (12.3%) aged 50 years or over had
      one or more vertebral deformities ("cases"). The cases were compared with the
      14,074 subjects (6,539 males, 7,535 females) with morphometrically normal spines
      ("controls"). Data were collected on self-reported height at age 25 years and
      minimum weight after age 25 years, as well as on current measured height and
      weight. Body mass index (BMI) and height and weight change were calculated from
      these data. The relations between these variables and vertebral deformity were
      examined separately by sex with logistic regression adjusting for age, smoking,
      and physical activity. In females, there was a significant trend of decreasing
      risk with increasing quintile of current weight, current BMI, and weight gain
      since age 25 years. In males, subjects in the lightest quintile for these
      measures were at increased risk but there was no evidence of a trend. An ecologic
      analysis by country revealed a negative correlation between mean BMI and the
      prevalence of deformity in females but not in males. The authors conclude that
      low body weight is associated with presence of vertebral deformity.

PMID- 9270408
TI  - Association of soy and fiber consumption with the risk of endometrial cancer.
AB  - The authors conducted a case-control study among the multi-ethnic population of
      Hawaii to examine the role of dietary soy, fiber, and related foods and nutrients
      on the risk of endometrial cancer. Endometrial cancer cases (n = 332) diagnosed
      between 1985 and 1993 were identified from the five main ethnic groups in the
      state (Japanese, Caucasian, Native Hawaiian, Filipino, and Chinese) through the
      rapid-reporting system of the Hawaii Tumor Registry. Population controls (n =
      511) were selected randomly from lists of female Oahu residents and matched to
      cases on age (+/-2.5 years) and ethnicity. All subjects were interviewed using a
      diet history questionnaire that included over 250 food items. Non-dietary risk
      factors for endometrial cancer included nulliparity, never using oral
      contraceptives, fertility drug use, use of unopposed estrogens, a history of
      diabetes mellitus or hypertension, and a high Quetelet's index (kg/cm2). Energy
      intake from fat, but not from other sources, was positively associated with the
      risk of endometrial cancer. The authors also found a positive, monotonic relation
      of fat intake with the odds ratios for endometrial cancer after adjustment for
      energy intake. The consumption of fiber, but not starch, was inversely related to
      risk after adjustment for energy intake and other confounders. Similar inverse
      gradients in the odds ratios were obtained for crude fiber, non-starch
      polysaccharide, and dietary fiber. Sources of fiber, including cereal and
      vegetable and fruit fiber, were associated with a 29-46% reduction in risk for
      women in the highest quartiles of consumption. Vitamin A and possibly vitamin C,
      but not vitamin E, were also inversely associated with endometrial cancer,
      although trends were not strong. High consumption of soy products and other
      legumes was associated with a decreased risk of endometrial cancer (p for trend =
      0.01; odds ratio = 0.46, 95% confidence interval 0.26-0.83) for the highest
      compared with the lowest quartile of soy intake. Similar reductions in risk were
      found for increased consumption of other sources of phytoestrogens such as whole
      grains, vegetables, fruits, and seaweeds. Ethnic-specific analyses were generally
      consistent with these results. The observed dietary associations appeared to be
      largely independent of other risk factors, although the effects of soy and
      legumes on risk were limited to women who were never pregnant or who had never
      used unopposed estrogens. These data suggest that plant-based diets low in
      calories from fat, high in fiber, and rich in legumes (especially soybeans),
      whole grain foods, vegetables, and fruits reduce the risk of endometrial cancer.
      These dietary associations may explain in part the reduced rates of uterine
      cancer in Asian countries compared with those in the United States.

PMID- 9270409
TI  - Breast cancer risk factors according to combined estrogen and progesterone
      receptor status: a case-control analysis.
AB  - Breast cancers demonstrate a gradient of responsiveness to endocrine therapy
      according to hormone receptor status, with tumors positive for both estrogen and
      progesterone receptors responding most favorably. The authors hypothesized that
      reproductive risk factors, which are probably mediated by endogenous hormones,
      would also differ according to receptor status, and that tumors positive for both
      receptors would exhibit the highest risk. Information on risk factors was
      obtained from 1,154 breast cancer cases and 21,714 cancer-free controls at the
      Aichi Cancer Center Hospital, Nagoya, Japan between 1988 and 1992. Receptor
      status was known for 40% of cases. For a given risk factor, odds ratios with
      respect to the common control group for breast cancers of differing receptor
      status were compared using multiple polytomous logistic regression. Risk factors
      did not differ significantly according to estrogen receptor status. However, age
      at diagnosis/interview, occupation, age at menarche, menstrual regularity at ages
      20-29 years, and cigarette smoking differed significantly or borderline
      significantly in effect according to progesterone receptor status. Stratification
      of cases according to joint estrogen and progesterone receptor status indicated
      that estrogen receptor status did not modify this difference in effect. This
      study did not support the hypothesis of a gradient of risk for reproductive
      factors according to hormone receptor status. The authors recommend that the
      finding that some risk factors differ according to progesterone receptor status
      should be pursued in further studies.

PMID- 9270410
TI  - Low insulin sensitivity is associated with clustering of cardiovascular disease
      risk factors.
AB  - Hyperinsulinemia is associated with multiple metabolic disorders including high
      triglyceride level, low high density lipoprotein (HDL) cholesterol level,
      hypertension, and impaired glucose tolerance (IGT). This metabolic constellation
      is also called the insulin resistance syndrome. All previous data on clustering
      of these risk factors are, however, based on insulin levels. Therefore, the
      authors examined the association of insulin sensitivity estimated by means of a
      frequently sampled intravenous glucose tolerance test and the minimal model with
      the number of metabolic disorders (dyslipidemia [high triglyceride level or low
      HDL cholesterol level or both], hypertension, and IGT according to the World
      Health Organization criteria). Of 153 nondiabetic subjects aged 53-61 years who
      had participated in a previous population-based study, 79 had no disorders, 55
      had one disorder, 16 had two disorders, and 3 had three disorders. Insulin
      sensitivity index (S1) decreased with the increasing number of disorders (4.1,
      3.5, 1.8, and 1.4 x 10(-4) min-1 microU-1 mL-1, in subjects with 0, 1, 2, and 3
      disorders, respectively; p < 0.001 for trend). Similarly, fasting (7.5, 7.8,
      15.3, and 22.0 microU/mL; p < 0.001) and 2-hour insulin levels (39.9, 49.0, 98.7,
      and 149.6 microU/mL; p < 0.001) increased by the increasing number of disorders.
      The relations of S1 and fasting and 2-hour insulin levels with multiple metabolic
      disorders were independent of sex, obesity, and body fat distribution.
      Furthermore, these associations were similar in men and women and in lean and
      obese subjects. The authors conclude that a clustering of cardiovascular disease
      risk factors in nondiabetic subjects is not only associated with hyperinsulinemia
      but also with insulin resistance.

PMID- 9270411
TI  - Physical activity and cardiovascular disease risk profile in women.
AB  - In a population of 4,576 Dutch women aged 49-70 years who participated in the
      European Prospective Investigation into Cancer and Nutrition (EPIC) in 1993-1995,
      the relation between physical activity and the presence of cardiovascular disease
      risk indicators was assessed cross-sectionally. Physical activity was determined
      from a self-administered questionnaire, while blood pressure, heart rate, body
      mass index, waist/hip ratio, and waist circumference were measured at the study
      center. Mean risk indicator levels were calculated for different activity
      categories. Blood pressure was most clearly associated with time spent in sports
      (mean systolic blood pressure, adjusted for age, level of education, and smoking,
      128.9 mmHg in the highest sports tertile, and 132.1 mmHg in the lowest sports
      tertile; mean diastolic blood pressure, 77.8 mmHg and 79.0 mmHg, respectively).
      Body mass index, waist/hip ratio, and waist circumference showed an inverse
      relation with cycling, gardening, do-it-yourself-activities, and sports. In this
      population, leisure-time activity was inversely related to cardiovascular disease
      risk indicators, but work activity and housework were not. The authors conclude
      that if investigators wish to measure physical activity in women over age 50
      years with the aim to identify high- and low-risk groups for cardiovascular
      disease, they should consider not only housework activity, but also leisure-time
      activities such as cycling, sports, and do-it-yourself activities.

PMID- 9270412
TI  - Gestational age, birth weight, and perinatal death among births to Norwegian
      farmers, 1967-1991.
AB  - Perinatal health was investigated by linkage with the Medical Birth Registry of
      Norway for 192,417 births that took place between 1967 and 1991 among parents
      identified as farm holders in Norwegian agricultural censuses in 1969-1989. In a
      comparison with 61,351 births to nonfarmers in agricultural municipalities,
      farmers' births had an advantageous distribution of gestational ages and birth
      weights. Perinatal mortality was similar in the two groups, but the proportion of
      late-term abortions (gestational weeks 16-27) was higher among farmers' birth
      (odds ratio (OR) = 1.9, 95% confidence interval (CI) 1.6-2.3). Exposure
      indicators were classified on the basis of information given in the agricultural
      censuses and climate data for the grain harvest seasons of 1966-1991. The main
      hypotheses were that perinatal death is associated with parental exposure to
      pesticides. Toxoplasma contracted from infected sheep or pigs, or mycotoxins
      found in grain farming. There was no convincing evidence that perinatal death is
      associated with use of pesticides, sheep farming, or pig farming. The increase in
      late-term abortion among the farmers could to some extent be attributed to an
      excess of midpregnancy (weeks 21-24) deliveries among grain farmers; grain
      farmers had 132 deliveries at this time in pregnancy (2.8 per 1,000 pregnancies),
      while the nongrain farmers had 236 deliveries in midpregnancy (1.8 per 1,000).
      The authors found odds ratios (95% CI) that indicated that grain farming risk was
      higher after the harvest (1.8, 1.1-2.8), in seasons with a poor quality harvest
      (2.4, 1.5-3.8), and in pregnancies with multiple births (3.8, 1.7-8.2). These
      results support the hypothesis that occupational exposure to mycotoxins in grain
      induces labor at an early stage of pregnancy.

PMID- 9270413
TI  - Hypothesis concerning the U-shaped relation between body mass index and
      mortality.
AB  - Numerous studies have documented a U- or J-shaped association between body mass
      index (BMI) (kg/m2) and mortality, such that increased mortality rate is
      associated with relatively low and high BMI values. It has been argued elsewhere
      that the elevated mortality rate observed at lower BMI values actually results
      from the effects of unmeasured confounding variables, in particular smoking
      status and preexisting disease. In this paper, the authors present an additional
      explanation for the phenomenon, i.e., nonspecific measurement. They propose that
      differential health consequences of fat mass and fat-free mass can be masked by
      the use of BMI when studied in relation to mortality. To illustrate this point,
      they use body composition data from 1,137 healthy adults and specify a
      hypothetical underlying BMI-mortality model in which the logit of death increased
      linearly with fat mass and decreased linearly with fat-free mass, and % fat
      increased monotonically with BMI. The results indicate that, even under these
      specifications, the authors can recover a U-shaped association between BMI and
      mortality. Consistent with previous suggestions in the literature, future
      epidemiologic studies that examine the association between adiposity and
      mortality should prioritize the use of body composition measures.

PMID- 9270414
TI  - Heterosexual transmission of human immunodeficiency virus (HIV) in northern
      California: results from a ten-year study.
AB  - To examine rates of and risk factors for heterosexual transmission of human
      immunodeficiency virus (HIV), the authors conducted a prospective study of
      infected individuals and their heterosexual partners who have been recruited
      since 1985. Participants were recruited from health care providers, research
      studies, and health departments throughout Northern California, and they were
      interviewed and examined at various study clinic sites. A total of 82 infected
      women and their male partners and 360 infected men and their female partners were
      enrolled. Over 90% of the couples were monogamous for the year prior to entry
      into the study; < 3% had a current sexually transmitted disease (STD). The median
      age of participants was 34 years, and the majority were white. Over 3,000 couple
      months of data were available for the follow-up study. Overall, 68 (19%) of the
      360 female partners of HIV-infected men (95% confidence interval (CI) 15.0-23.3%)
      and two (2.4%) of the 82 male partners of HIV-infected women (95% CI 0.3-8.5%)
      were infected. History of sexually transmitted diseases was most strongly
      associated with transmission. Male-to-female transmission was approximately eight
      times more efficient than female-to-male transmission and male-to-female per
      contact infectivity was estimated to be 0.0009 (95% CI 0.0005-0.001). Over time,
      the authors observed increased condom use (p < 0.001) and no new infections.
      Infectivity for HIV through heterosexual transmission is low, and STDs may be the
      most important cofactor for transmission. Significant behavior change over time
      in serodiscordant couples was observed.

PMID- 9270415
TI  - Re: "Cryptosporidiosis among patients infected with human immunodeficiency virus:
      factors related to symptomatic infection and survival".

PMID- 9270416
TI  - Re: "Water, waste, and well-being: a multicountry study".

PMID- 9270417
TI  - Re: "Exposure to polychlorinated dioxins and furans (PCDD/F) and mortality in a
      cohort of workers from a herbicide-producing plant in Hamburg, Federal, Republic
      of Germany".

PMID- 9270418
TI  - Re: "A new perspective on John Snow's communicable disease theory".

PMID- 9270419
TI  - Re: "Family history of cancer and risk of lung cancer among lifetime nonsmoking
      women in the United States".

PMID- 9270420
TI  - Re: "Sex difference in high density lipoprotein cholesterol in six countries".

PMID- 9270421
TI  - Re: Electromagnetic field exposure and lung cancer.

PMID- 9270422
TI  - Role of adenoids in the pathogenesis of otitis media: a bacteriologic and
      immunohistochemical analysis.
AB  - Adenoidectomy is frequently performed in children suffering from recurrent or
      chronic otitis media with effusion and is thought to produce a long-term effect
      in preventing further episodes of otitis media. Bacteriologic analysis of
      adenoids from 60 patients revealed a significantly elevated colonization rate of
      middle ear pathogens in children with a present or previous history of ear
      disease compared to children with adenoidal hypertrophy only. The predominant
      pathogen was nontypeable Haemophilus influenzae, followed by Streptococcus
      pneumoniae and Moraxella catarrhalis. Quantitative analysis did not demonstrate a
      bacterial overload in the otitis group. Lectin histochemical analysis of the
      adenoids revealed no significant differences between the three groups;
      nevertheless, colonization with S pneumoniae demonstrated an increased labeling
      pattern with succinylated wheat germ agglutinin, indicating the exposure of N
      acetyl-glucosamine as part of its own receptor structure. On the basis of these
      results, we support the concept of adenoidectomy in order to remove a bacterial
      focus; however, we could not verify the hypothesis of bacterial overgrowth in the
      nasopharynx.

PMID- 9270423
TI  - Distribution and heritability of recurrent ear infections.
AB  - The distribution of recurrent ear infections was obtained from a population-based
      sample of 2,750 pairs of Norwegian twins born between 1967 and 1974. The lifetime
      prevalence of self-reported recurrent ear infections was 8.9%, with a significant
      predominance of female cases. The mean age of onset was 4.2 years, with a gradual
      decrease in occurrence from 2 to 7 years of age. Among monozygotic pairs, the
      rate of tetrachoric correlation between co-twins was almost identical in males
      (0.73, SE 0.08) and females (0.74, SE 0.06), but among the dizygotic pairs the
      correlation was clearly higher in males (0.53, SE 0.12) than in females (0.20, SE
      0.12). The value in the unlike-sexed dizygotic twins (0.25, SE 0.05) was
      intermediate to that of the like-sexed male and female dizygotic pairs. The
      relative contribution of genes and environment to variability in the
      predisposition to develop otitis media was estimated by means of structural
      equation modeling. Variation in liability to ear infections was mainly explained
      by additive genetic and dominance factors in females, for whom heritability was
      estimated at 74%. The remaining 26% of the variation in liability was explained
      by individual environmental factors. In males, 45% of the variation could be
      accounted for by genetic factors, 29% by common familial environment, and the
      remaining 26% by individual environmental effects.

PMID- 9270425
TI  - Reversible sensorineural hearing loss after renal transplant immunosuppression
      with OKT3 (muromonab-CD3).
AB  - Reversible and irreversible ototoxicity has been documented following the
      administration of various therapeutic agents. Reversible hearing loss is a known
      complication following the administration of quinine, salicylates and other
      nonsteroidal anti-inflammatory drugs, and erythromycin. We report a case of
      reversible hearing loss following OKT3 (murine monoclonal antibody CD3)
      administration. OKT3, a monoclonal antibody used as an immunosuppressant
      following cadaveric renal transplants, was associated with a transient
      sensorineural hearing loss that reversed following discontinuation of OKT3.

PMID- 9270424
TI  - Role of tumor necrosis factor and interleukin-1 in endotoxin-induced middle ear
      effusions.
AB  - In a rat model, we investigated the role of tumor necrosis factor (TNF) and
      interleukin-1 (IL-1) in endotoxin-induced middle ear effusions (MEEs). After the
      eustachian tube was obstructed, the middle ear was transtympanically injected
      with 35 microL of either 1) 1 mg/ mL lipopolysaccharide (LPS); 2) LPS and 100
      micrograms TNF binding protein (TNFbp); 3) LPS and 1 microgram IL-1 receptor
      antagonist (IL-1ra); or 4) LPS, TNFbp, and IL-1ra. Every 2 hours, the fluid
      within the middle ear was collected, and the quantity of albumin in the fluid, an
      index of vascular leakage, was determined by enzyme-linked immunosorbent assay.
      After 6 hours, the middle ear was fixed for histologic analysis. The TNFbp
      significantly attenuated vascular extravasation into the middle ear. The IL-1ra
      did not significantly alter effusion development. These results indicate that
      TNF, but not IL-1, is a mediator of LPS-induced MEE. Therefore, TNFbp may
      represent a novel approach to the treatment of otitis media with effusion.

PMID- 9270426
TI  - Audiologic features of hearing loss due to the 1,555 mutation of mitochondrial
      DNA.
AB  - We proved a 1,555 mutation of mitochondrial DNA in one member of each of three
      families with familial streptomycin hearing loss, and report the pedigrees and
      audiologic features. DNA was extracted by the standard method. The 1,555 A to G
      mutation was identified in all three patients and confirmed by direct sequencing
      of the polymerase chain reaction products by a cycle sequencing method. On
      audiograms, the hearing loss was sensorineural, bilateral, and symmetric, showing
      a high-tone loss or a profound loss particularly in the high-tone range, and the
      "symmetry law" of Langenbeck was applicable. The superimposed audiograms of
      members of one family did not cross themselves, proving the applicability of the
      "never-cross principle of audiograms."

PMID- 9270427
TI  - Anaerobes and fungi in chronic suppurative otitis media.
AB  - Microbiology of 102 ears with chronic suppurative otitis media was studied for
      aerobes, anaerobes, and fungi. Forty-four percent were pure cultures, 33.3% were
      mixed, and 18.6% had no growth. Seventy-four percent were aerobes, 25% fungi, and
      only 0.9% anaerobes. Pseudomonas aeruginosa (22.5%) was the most common isolate,
      followed by Staphylococcus aureus and the Aspergillus species. The possible
      reasons for low yield of anaerobes and the pathogenic roles of anaerobes and
      fungi in chronic suppurative otitis media are discussed. It is advocated that in
      investigating pathogenic organisms in chronic suppurative otitis media, requests
      should include anaerobes and fungi.

PMID- 9270428
TI  - Electrical impedance of the cochlear implant lubricants hyaluronic acid,
      oxycellulose, and glycerin.
AB  - Hyaluronic acid (Healon), oxycellulose (hydroxypropyl methylcellulose), and
      glycerin are lubricants used in cochlear implant surgery for atraumatic deep
      insertion of the electrode array into the scala tympani. The electrical
      impedances of these three lubricants were measured to assess possible effects on
      intraoperative evoked response measurements, such as the electrically evoked
      stapedius reflex and auditory brain stem response. The impedances of hyaluronic
      acid, oxycellulose, and saline were very similar and independent of frequency (20
      Hz to 1 MHz). Glycerin had an excessively high impedance at low frequencies. A
      film of hyaluronic acid or oxycellulose around the electrode array immersed in
      saline did not have any measurable effect on the impedance; a film of glycerin
      resulted in a strongly reactive polarized layer. However, neither the far-field
      current spread nor the impedance between stimulated electrodes was affected by
      any of the lubricants applied as a thin film. This suggests that none of these
      lubricants affect intraoperative responses, when applied as a thin film.

PMID- 9270429
TI  - Meningioma of the internal auditory canal.
AB  - Meningiomas are the second most common tumor to involve the cerebellopontine
      angle (CPA), but controversy exists as to whether they can arise within the
      internal auditory canal (IAC) or whether involvement of the IAC occurs
      secondarily by extension from the CPA. This paper reports on a patient with an
      enhancing IAC meningioma that then grew and on subsequent scans was found to
      involve the CPA. This case demonstrates that these tumors can arise within the
      IAC and can grow out to involve the CPA. These findings are discussed within the
      context of meningioma tumor genetics and the histologic evidence for precursor
      cells in the IAC. The radiologic findings useful in distinguishing an acoustic
      neuroma from a meningioma are reviewed in the light of this case. While an
      enhancing mass projecting into the IAC is most often an acoustic neuroma, this
      radiologic findings is not pathognomonic.

PMID- 9270430
TI  - Immunohistochemistry of lymphocytes and macrophages in human celloidin-embedded
      temporal bone sections with acute otitis media.
AB  - Immunohistochemical analyses were used to investigate the distribution of
      lymphocytes and macrophages in routine human temporal bone sections obtained from
      a subject with acute suppurative otitis media. Primary antibodies specific for
      human CD3 and CD43 (T-lymphocytes), CD20 (B-lymphocytes), CD45 (leukocyte common
      antigen), and CD68 (macrophages) were used. As a pretreatment, the sections were
      soaked in antigen retrieval solution (saturated sodium hydroxide-methanol
      solution in methanol at a ratio of 1:3). A second antigen retrieval procedure
      (microwave treatment in 1% zinc sulfate) was also employed for identifying CD3
      positive cells. Then the avidin-biotin-peroxidase complex technique was
      performed. Positive reactions to all antibodies but anti-CD68 were observed in
      the mucosa of the eustachian tube, tympanic cavity, and mastoid air cells.
      Particularly, cells positive to anti-CD3 or anti-CD43 were making a diffuse
      invasion upon the lamina propria. CD68-positive cells were scattered only in the
      effusion of mastoid air cells. These results suggest that the retrospective
      immunohistochemical study of archival temporal bone sections is a promising
      approach to investigate the pathogenesis of otitis media.

PMID- 9270431
TI  - Localization of transforming growth factor-beta-expressing cells and comparison
      with major extracellular components in aural cholesteatoma.
AB  - Transforming growth factor-beta (TGF-beta) plays an important role in the
      regulation of extracellular matrix (ECM) deposition by stimulating the synthesis
      of individual matrix proteins like tenascin and fibronectin. Cholesteatoma shows
      significant changes in the ECM, supporting the view of a disturbed cell-matrix
      interaction. The purpose of our present study was to evaluate the distribution of
      TGF-beta in comparison to the deposition of tenascin, fibronectin, and collagen
      as major components of the ECM in cholesteatoma (n = 12) by means of
      histochemistry and immunohistochemistry. We found TGF-beta in lymphocytes and
      fibrohistiocytes in the stroma of 7 cholesteatomas. In corresponding sections, a
      marked expression of tenascin and fibronectin was seen manifesting as a
      continuous band along the epidermal-stromal junction, extending to the deeper
      stroma. In addition, in those cases of TGF-beta expression, beginning collagen
      fibril formation was seen in adjacent deeper stroma layers, indicating beginning
      stromal fibrosis. These results suggest that TGF-beta may be involved in the
      stimulation of the synthesis of tenascin, fibronectin, and collagen. Furthermore,
      the enhanced expression of tenascin and fibronectin provides evidence for a
      deregulated cell-matrix interaction in cholesteatoma associated with the enhanced
      proliferative process of cholesteatoma formation.

PMID- 9270432
TI  - Clinicopathologic study of leptomeningeal carcinomatosis involving the temporal
      bone.
AB  - The temporal bone pathology of a 71-year-old man with bilateral sensorineural
      hearing loss and facial paralysis caused by diffuse metastatic leptomeningeal
      carcinomatosis is described. The origin of this malignant disease was an
      extremely rare entity, a transitional cell carcinoma of the renal pelvis.
      Histopathologic study of the temporal bone demonstrated that tumor cells filled
      the internal auditory meatus, infiltrated into the Rosenthal's canals, and
      reached the scala tympani of the basal turn of the bilateral cochleas. The
      vestibulocochlear nerve and facial nerve trunks in the internal auditory meatus
      had been destroyed by the bilateral tumor invasion. Case reports of temporal bone
      metastases of leptomeningeal carcinomatosis published since 1965 were reviewed.
      In leptomeningeal carcinomatosis, it is suggested that tumor cells infiltrate the
      internal auditory meatus of both ears simultaneously from the cerebrospinal
      fluid, involving the seventh and eighth nerve trunks, and then cause bilateral
      sensorineural hearing loss and facial paralysis.

PMID- 9270433
TI  - Effect of photodynamic therapy on selected laboratory values of patients with
      nasopharyngeal carcinoma.
AB  - We determined pre- and post-photodynamic therapy (PDT) serum levels of soluble
      interleukin-2 receptor (SIL-2R) and interleukin-2 (IL-2), as well as activity of
      natural killer (NK) cells, among 24 patients with either persistent or recurrent
      nasopharyngeal carcinoma (NPC), using a double-antibody sandwich technique,
      tritiated thymidine-deoxyribonucleoside incorporation, and iodine 125-uridine
      deoxyribonucleoside release techniques, respectively. The results showed that the
      post-PDT serum level of SIL-2R had significantly declined (p < .0005), while that
      of IL-2 and the NK cell activity had significantly increased (p < .0005),
      compared with pre-PDT values, suggesting an immunoenhancing effect of PDT on NPC
      patients.

PMID- 9270434
TI  - Effects of indomethacin, dexamethasone, and erythromycin on endotoxin-induced
      intraepithelial mucus production of rat nasal epithelium.
AB  - We produced hypertrophic and metaplastic changes of goblet cells in rat nasal
      respiratory epithelium by the intranasal instillation of endotoxin (ETN). In the
      present study, we examined in vivo effects of indomethacin (IND), dexamethasone
      (DEX), and erythromycin (EM) on intraepithelial mucus production using this
      animal model. Intraperitoneal injection of IND (2 to 4 mg/kg body weight x 4
      days) or DEX (4 to 8 mg/kg body weight x 4 days) significantly inhibited
      intraepithelial mucus production induced after 3 days of ETN instillations.
      Intraperitoneal injection of EM (100 mg/kg body weight x 8 days),
      aminobenzylpenicillin (ABPC, 200 mg/kg body weight x 8 days), and cephalothin
      (CET, 200 mg/kg body weight x 8 days) also inhibited intraepithelial mucus
      production induced after 7 days of ETN instillations. When compared with ABPC and
      CET, EM had a greater inhibitory effect. These results indicate that ETN-induced
      intraepithelial mucus production can be inhibited by treatment with the anti
      inflammatory drugs IND and DEX. Antibiotics such as EM, ABPC, and CET will also
      be effective, probably by preventing secondary bacterial infection, and EM has an
      additional inhibitory effect on intraepithelial mucus production.

PMID- 9270435
TI  - Origin and distribution of NADPH diaphorase-positive nerves in rat nasal mucosa.
AB  - The aim of this study was to localize the distribution of (reduced) nicotinamide
      adenine dinucleotide phosphate (NADPH) diaphorase-positive nerves in the rat
      nasal mucosa by NADPH diaphorase histochemistry, and to determine its origin by
      utilizing retrograde tracing with Fluoro-Gold (FG). Fine varicosities of NADPH
      diaphorase-positive nerve fibers were distributed around blood vessels
      (arterioles in particular), submucosal glands, and the subepithelial layer of the
      nasal mucosa. Most of the ganglion cells and nerve fibers in the sphenopalatine
      ganglion, and a few ganglion cells in the trigeminal ganglion, were stained by
      NADPH diaphorase, but no NADPH diaphorase-positive ganglion cells were found in
      the superior cervical ganglion. Retrograde tracing with FG and co-localization of
      NADPH diaphorase demonstrated that the FG-labeled ganglion cells in the
      sphenopalatine ganglion were NADPH diaphorase-positive, but the FG-labeled
      ganglion cells in both the trigeminal and the superior cervical ganglia were
      NADPH diaphorase-negative. In conclusion, NADPH diaphorase-positive nerves
      distribute around blood vessels, around submucosal glands, and in the
      subepithelial layer of the rat nasal mucosa, and their origin is the
      sphenopalatine ganglion. These findings imply that nitric oxide may be co
      localized to the cholinergic innervation and be involved in vasomotor and
      secretomotor control of the nasal mucosa.

PMID- 9270436
TI  - Impact of a laryngectomy on quality of life: perspective of the patient versus
      that of the health care provider.
AB  - This study retrospectively assesses the impact of laryngectomy on the quality of
      life of 46 patients as compared to the perception of the impact of laryngectomy
      of 13 health care providers (HCPs). Employing the "time trade-off" methodology,
      we assessed patient and HCP preferences and calculated estimated utilities. We
      found that 20% of patients would be willing to compromise anticipated life
      expectancy to preserve voice or preoperative quality of life. By comparison, 46%
      of the HCPs perceived that their patients would be willing to accept a reduced
      life span in order to preserve their larynx and quality of life. In conclusion,
      the percentage of HCPs who believed their patients would compromise survival was
      substantially higher than the percentage of actual patients who expressed this
      preference. This perception may influence physicians' attitudes toward
      recommending laryngeal preservation therapy for their patients. For most
      laryngectomy patients, treatments attempting laryngeal preservation, particularly
      if associated with compromised survival, may not be warranted.

PMID- 9270437
TI  - Glottic-supraglottic barrier: fact or fantasy?
AB  - An anatomic structure that might act as a barrier between the glottic and
      supraglottic areas has never been demonstrated in whole organ serial section
      studies. Nevertheless, most squamous cell carcinomas arising on the supraglottic
      mucosa remain confined above the ventricle, and this fact is reflected in the
      high rate of local control obtained by surgeons performing horizontal
      supraglottic laryngectomy: 80.6% to 98%. Whole organ sections of laryngectomy
      specimens suggest that a tumor situated above and below the glottic level may
      have arrived there not by crossing the ventricle, but by encircling it. In so
      doing, part of the tumor is visible posterior to the ventricle or on the
      arytenoid cartilage-a finding that contraindicates conventional supraglottic
      laryngectomy, with or without limited mobility of the true vocal cord.

PMID- 9270438
TI  - Role of flexible laryngoscopy in evaluating aspiration.
AB  - Flexible fiberoptic laryngoscopy is used to evaluate dysphagia, but its clinical
      utility has not been compared to that of the videofluorographic swallowing study
      (VFSS). This study correlates parameters of both procedures and identifies
      laryngoscopic predictors of aspiration in 105 patients. Presence of aspiration,
      pharyngeal residue, laryngeal sensation, vocal cord mobility, and glottic closure
      during flexible laryngoscopy (FL), and gag reflex were correlated with aspiration
      during the VFSS. An algorithm for laryngoscopically detecting aspiration was
      synthesized. Aspiration (p = .004) and pharyngeal residue (p < .00001) were
      highly correlated between the two studies. Aspiration during the VFSS was
      correlated with pharyngeal residue (p < .00001) and laryngeal sensation (p =
      .027) during FL, but not glottic closure (p = .169) nor vocal cord mobility (p =
      .056). Patients with a normal gag reflex and without aspiration or pharyngeal
      residue during FL had a 2.94% risk of aspiration during the VFSS. Flexible
      laryngoscopy can be used as a relatively safe, portable screening test for
      aspiration, but cannot always replace the VFSS to identify the presence or cause
      of aspiration.

PMID- 9270439
TI  - Knife blade as a facial foreign body.
AB  - This case demonstrates the unpredictability of foreign bodies in the face. The
      retained knife blade eluded detection on two separate examinations. The essential
      components to making a correct diagnosis of a foreign body following a stabbing
      to the face include a thorough review of the mechanism of injury, a complete head
      and neck examination, a high index of suspicion, and plain radiographs of the
      face.

PMID- 9270440
TI  - Osteoma of the middle ear.

PMID- 9270441
TI  - Barrier between the supraglottis and the glottis: myth or reality?
AB  - Controversial opinions on the existence of a "barrier" between the supraglottic
      and glottic regions of the larynx are reported. Even if the two areas have
      different embryological derivations, there is no anatomic evidence of a "barrier"
      that could prevent supraglottic cancer from extending downward to the glottis.
      Numerous adequate pathologic studies, including whole organ sections, confirm
      that for advanced cancers, anatomic compartments delimiting the spread of the
      neoplastic process from the supraglottis to the glottis do not exist. Therefore,
      supraglottic laryngectomy should be performed not on the basis of embryological
      considerations, but on the basis of the actual extension of the neoplastic
      lesion.

PMID- 9270442
TI  - Acute otitis media in children.

PMID- 9270443
TI  - Kawasaki disease.

PMID- 9270444
TI  - Clinical guidelines.

PMID- 9270446
TI  - Educating doctors, to improve patient care.

PMID- 9270445
TI  - Why Britain's drug czar mustn't wage war on drugs.

PMID- 9270447
TI  - Row over force feeding of patients with Alzheimer's disease.

PMID- 9270448
TI  - Experimental angina treatment rejected by the FDA.

PMID- 9270449
TI  - Nuclear test fallout linked to cancer risk.

PMID- 9270450
TI  - Asthma drug linked with Churg-Strauss syndrome.

PMID- 9270451
TI  - Canadians sue over hepatitis C infection.

PMID- 9270452
TI  - United States budget supports child health.

PMID- 9270453
TI  - Systematic review of role of polymerase chain reaction in defining infectiousness
      among people infected with hepatitis C virus.
AB  - OBJECTIVE: To assess the role of polymerase chain reaction in defining
      infectiousness among people infected with hepatitis C virus. DESIGN: Published
      studies of hepatitis C transmission were examined. Twenty nine studies with
      identified sources of hepatitis C infection who were tested for presence of
      hepatitis C RNA by polymerase chain reaction were reviewed, including studies of
      vertical transmission (n = 21), transmission after transplantation (n = 3),
      transfusion of blood components (n = 3), and needlestick exposure (n = 2).
      SUBJECTS: All patients identified in studies. RESULTS: A total of 2022 people who
      had been exposed to sources positive for antibody to hepatitis C were identified.
      Among 1148 people exposed to sources positive by polymerase chain reaction 148
      cases of transmission occurred compared with no definite case among 874 people
      exposed to negative sources. Rates of transmission from positive sources were
      6.2% for perinatal exposure, 6.1% after needlestick exposure, 78% after solid
      organ or bone marrow transplantation, and 83% after transfusion of blood
      components. Other factors influencing risk of vertical transmission were
      coinfection with HIV and level of hepatitis C viraemia. CONCLUSIONS: Negative
      results by polymerase chain reaction indicate an extremely low probability of
      transmission of hepatitis C from a person with antibody to hepatitis C.

PMID- 9270454
TI  - Evaluation of validity of British anthropometric reference data for assessing
      nutritional state of elderly people in Edinburgh: cross sectional study.
AB  - OBJECTIVES: To evaluate the appropriateness of two sets of commonly used
      anthropometric reference data for nutritional assessment of elderly people.
      DESIGN: Cross sectional study. SETTING: Two general practices in Edinburgh.
      SUBJECTS: 200 independently living men and women aged 75 or over randomly
      recruited from the age and sex register of the practices. MAIN OUTCOME MEASURES:
      Weight (kg), knee height (cm), demispan (cm), mid-upper arm circumference (cm),
      triceps skinfold thickness (mm), arm muscle circumference (cm) body mass index
      (kg/m2), and demiquet (kg/m2) in men and mindex (kg/m) in women. RESULTS: Men and
      women in Edinburgh were significantly shorter than those in measured for the
      Nottingham reference data (demispan 0.79 v 0.80 (P < 0.05) for men and 0.72 v
      0.73 (P < 0.01) for women). Comparison with data from South Wales showed that men
      and women from Edinburgh had significantly greater mid-upper arm circumference,
      triceps skinfold thickness, and arm muscle circumference. No one fell below the
      10th centile of the South Wales data (the commonly used out off point for
      determining malnutrition) for these measures. CONCLUSIONS: Both sets of reference
      data commonly used in Britain may be inappropriate for nutritional screening of
      elderly people in Edinburgh. Contemporary reference data appropriate for the
      whole of Britain need to be developed, and in the longer term biologically or
      clinically defined criteria for undernutrition should be established.

PMID- 9270455
TI  - Reduced final height and indications for insulin resistance in 20 year olds born
      small for gestational age: regional cohort study.
AB  - OBJECTIVE: To investigate whether the association between low birth weight and
      increased risk of developing impaired glucose tolerance, insulin resistance,
      hypertriglyceridaemia, and hypertension in middle age is apparent by the age of
      20 in people born small for gestational age. DESIGN: Regional cohort study.
      SETTING: Maternity registry, Haguenau, France. SUBJECTS: 236 full term singleton
      babies born small for gestational age (birth weight or length, or both, below
      third centile) during 1971-8 and 281 with normal birth weight (between 25th and
      75th centile). All subjects were contacted and evaluated at a mean (SD) age of
      20.6 (2.1) years. MAIN OUTCOME MEASURES: Adult height; concentrations of glucose,
      insulin, and proinsulin during an oral glucose tolerance test; lipid and
      fibrinogen concentrations; and blood pressure. RESULTS: After sex and target
      height were adjusted for, subjects who had been born small for gestational age
      were significantly shorter at age 20 than those with a normal birth weight (men
      4.5 cm shorter (95% confidence interval 6.0 to 3.0 cm); women 3.94 cm shorter
      (5.2 to 2.7 cm)). After sex and body mass index were adjusted for, mean plasma
      glucose concentration 30 minutes after a glucose load, fasting insulin
      concentration (in women), and insulin and proinsulin concentrations 30 and 120
      minutes after a glucose load were significantly higher in subjects who had been
      born small for gestational age than in those with a normal birth weight. Mean
      lipid and fibrinogen concentrations and blood pressure were not different between
      the two groups. CONCLUSIONS: Intrauterine growth retardation has long term
      consequences such as reduced final height Raised insulin and proinsulin
      concentrations are present in young adults born small for gestational age and
      could be markers of early changes in insulin sensitivity.

PMID- 9270456
TI  - Survey of occupancy of paediatric intensive care units by children who are
      dependent on ventilators.

PMID- 9270457
TI  - Comparison of blood or urine testing by patients with newly diagnosed non-insulin
      dependent diabetes: patient survey after randomised crossover trial.

PMID- 9270458
TI  - Reattendance and complications in a randomised trial of prescribing strategies
      for sore throat: the medicalising effect of prescribing antibiotics.
AB  - OBJECTIVE: To assess the medicalising effect of prescribing antibiotics for sore
      throat. SETTING: 11 general practices in England. DESIGN: Randomised trial of
      three approaches to sore throat: a 10 day prescription of antibiotics, no
      antibiotics, or a delayed prescription if the sore throat had not started to
      settle after three days. PATIENTS: 716 patients aged 4 and over with sore throat
      and an abnormal physical sign: 84% had tonsillitis or pharyngitis. OUTCOME
      MEASURES: Number and rate of patients making a first return with sore throat,
      pharyngitis, or tonsillitis. Early returns (within two weeks) and complications
      (otitis media, sinusitis, quinsy). Outcomes were documented in 675 subjects
      (94%). RESULTS: Mean follow up time was similar (antibiotic group 1.07 years,
      other two groups 1.03 years). More of those initially prescribed antibiotics
      initially returned to the surgery with sore throat (38% v 27%, adjusted hazard
      ratio for return 1.39%, 95% confidence interval 1.03 to 1.89). Antibiotics
      prescribed for sore throat during the previous year had an additional effect
      (hazard ratio 1.69, 1.20 to 2.37). Longer duration of illness (> 5 days) was
      associated with increased return within six weeks (hazard ratio 2.90, 1.70 to
      4.92). Prior attendance with upper respiratory conditions was also associated
      with increased reattendance. There was no difference between groups in early
      return (13/238 (5.5%) v 27/437 (6%)), or complications (2/236 (0.8%) v 3/434
      (0.7%)). CONCLUSIONS: Complications and early return resulting from no or delayed
      prescribing of antibiotics for sore throat are rare. Both current and previous
      prescribing for sore throat increase reattendance. To avoid medicalising a self
      limiting illness doctors should avoid antibiotics or offer a delayed prescription
      for most patients with sore throat.

PMID- 9270459
TI  - Finance, not learning needs, makes general practitioners attend courses: a
      database survey.

PMID- 9270460
TI  - Recent advances. Otorhinolaryngology.

PMID- 9270461
TI  - ABC of mental health. Addiction and dependence--II: Alcohol.

PMID- 9270462
TI  - The search for evidence of effective health promotion.

PMID- 9270463
TI  - How to read a paper. Statistics for the non-statistician. I: Different types of
      data need different statistical tests.

PMID- 9270464
TI  - Obstructive sleep apnoea. False impression of objectivity may deny patients
      affordable treatment.

PMID- 9270465
TI  - Obstructive sleep apnoea. Superficial analysis ignores evidence on efficacy of
      treatment.

PMID- 9270466
TI  - Obstructive sleep apnoea. Evidence for efficacy of continuous positive airways
      pressure is compelling.

PMID- 9270467
TI  - Obstructive sleep apnoea. Review was misleading and may deny cost effective
      treatment to patients.

PMID- 9270468
TI  - Obstructive sleep apnoea. Treatment prevents road accidents, injury, and death
      caused by daytime sleepiness.

PMID- 9270469
TI  - Obstructive sleep apnoea. Some criticisms of studies are unfounded.

PMID- 9270470
TI  - Hazards of running a marathon. 41-Fold increase in creatine kinase has been
      reported.

PMID- 9270471
TI  - Hazards of running a marathon. Troponin-T concentrations should be measured.

PMID- 9270472
TI  - Unexpected findings of study of selegiline have not been treated with caution its
      authors advised.

PMID- 9270473
TI  - Drug treatment for benign prostatic hyperplasia. Health authorities must audit
      use of finasteride.

PMID- 9270474
TI  - Drug treatment for benign prostatic hyperplasia. Several trials have shown
      benefit of finasteride.

PMID- 9270475
TI  - Drug treatment for benign prostatic hyperplasia. To interpret PSA concentrations
      in patients taking finasteride, multiply them by two.

PMID- 9270476
TI  - Criticism of prophylaxis of gastrointestinal bleeding with H2 receptor
      antagonists is wrong.

PMID- 9270477
TI  - Treatment of pregnant women with recurrent miscarriage associated with
      phospholipid antibodies. General prognosis is favourable in untreated women.

PMID- 9270478
TI  - Treatment of pregnant women with recurrent miscarriage associated with
      phospholipid antibodies. No cytogenetic data were reported.

PMID- 9270480
TI  - Casualties of Gulf war were higher than most reports suggest.

PMID- 9270479
TI  - Treatment of pregnant women with recurrent miscarriage associated with
      phospholipid antibodies. During pregnancy, heparin should be stopped during
      labour and then restarted soon after delivery.

PMID- 9270481
TI  - Toward a National Information System for traumatic brain injury: foreword and
      overview.

PMID- 9270482
TI  - Establishing a national traumatic brain injury information system based upon a
      unified data set.
AB  - In alliance with payers and persons with disabilities, rehabilitation
      professionals can create an outcome data system for traumatic brain injury (TBI)
      that will provide the knowledge necessary to improve the effectiveness and cost
      effectiveness of rehabilitation programs. A nationwide TBI data system is needed
      to identify reasonably homogeneous subgroups given different treatments whose
      outcomes can be meaningfully compared. The advantages of a national outcome data
      system for gathering and analyzing this information include large sample sizes,
      objective assessment, measurement across the whole continuum of care, and
      adequate severity adjusters. Proposed methods and content for such a database are
      described, for reflecting general functional levels of clients along the
      continuum of care: acute care, TBI rehabilitation programs, and the community.
      Tools proposed are brief, have proven reliability and validity, and measure
      characteristics common to traumatically brain injured individuals. Possible data
      analysis approaches for a National Information System (database) dedicated to TBI
      are described for discussion within the rehabilitation community.

PMID- 9270483
TI  - Prognostic indicators in medical rehabilitation of traumatic brain injury: a
      commentary and review.
AB  - The National Information System (NIS) project is developing consensus opinion
      regarding a proposed structural framework for the prognostic data to be collected
      as part of this proposed multicenter research effort on severe traumatic brain
      injury (TBI). This article provide a brief history of the process, examines
      challenges facing rehabilitation research in this particular area, discusses
      reasons for identifying prognostic data within the research context of the NIS
      project, and describes methodologies for use of mathematical models in predicting
      outcome from TBI. The literature regarding prognostic parameters in severe TBI is
      briefly reviewed, utilizing three broad parameter categorizations: preinjury,
      injury, and postinjury. The implications of this research and directions for
      further study within the NIS project are discussed.

PMID- 9270484
TI  - Postacute neurorehabilitation: roles and responsibilities within a national
      information system.
AB  - The definition of a "postacute neurorehabilitation provider" has broadened
      considerably in the last 10 years. The postacute domain, once the purview of
      community re-entry (aka transitional) programs now includes hospital-based day
      and outpatient services, home health agencies, assisted living programs, subacute
      programs, and employment agencies to name but a few. Consequently, a range of
      outcome variables are considered, in large part as related to the clinical and/or
      business missions of the providers. This article reviews the postacute
      neurorehabilitation outcome literature with an eye toward establishing a
      concensus as to what outcomes are germane to these providers, with the patients
      and payers as the preferred primary consumers of the outcome-related information.

PMID- 9270485
TI  - Traumatic brain injury: designing and implementing a population-based follow-up
      system.
AB  - Craig Hospital and the Colorado Department of Public Health and Environment began
      designing a population-based follow-up system for persons with traumatic brain
      injury (TBI) in 1994. With funding from the Centers for Disease Control and
      Prevention, the Colorado TBI Follow-up System addresses the issue, "What happens
      to persons with TBI after they are discharged from the hospital?" Two methods of
      data collection are used, medical record review and annual telephone surveys to
      gather long-term outcomes. The design calls for following all persons
      hospitalized with severe TBI (defined as any person with inpatient rehabilitation
      and/or with an Abbreviated Injury Scale [AIS] score for the head of 3 or greater)
      and a 20% random sample of persons hospitalized with less severe TBI. An expert
      panel was used to select variables for retrospective abstracting and prospective
      interviewing. Information obtained from medical records includes data verifying
      eligibility, diagnoses, radiological results, circumstances of injury, and
      severity of injury, as well as demographic data. The interview instrument
      includes questions and scales related to health status, disability, handicap,
      quality of life, and service utilization. Both methods of data collection have
      been pilot-tested and are now used routinely in the Colorado TBI Follow-up
      System.

PMID- 9270486
TI  - Accreditation and the use of outcomes-oriented information systems.
AB  - Rehabilitation programs of all types and sizes must be able to use information
      technology to respond to both internal and external forces. One can anticipate
      that consumer-driven care will mean a desire for and access to more public
      information about health plans, specialty components of health care (eg,
      rehabilitation), and the quality of plans and providers. Providers need
      information with which to plan and manage their outcomes and resource allocation,
      to monitor and improve the quality of services, and to communicate with external
      stakeholders. The Commission on Accreditation of Rehabilitation Facilities (CARF)
      has for more than two decades required accredited organizations to have active
      outcome-oriented program evaluation systems. Yet, accreditation requirements have
      historically been process-oriented. This process orientation is now evolving
      toward an outcome orientation, both in the accreditation environment at large,
      and at CARF. This article describes these outcome-oriented initiatives, including
      CARF SCoRsSM, a standards conformance rating system under development at CARF,
      and a project to identify a limited, uniform set of performance indicators for
      rehabilitation programs. In addition, the article reflects on the significance of
      a potential National Information System for brain injury to the accreditation and
      outcomes arena.

PMID- 9270487
TI  - The missing link: structured dialogue between the payer and provider communities
      on the costs and benefits of medical rehabilitation.
AB  - The costs of medical rehabilitation for catastrophically injured people are
      significant. To be competitive in the market-place, third-party payers must
      provide high quality care to their insured populations while guarding against
      paying for unnecessary or ineffective services. The provider community,
      meanwhile, has developed new, lower-cost treatment programs for their patient
      populations. The proper use of all treatment options relative to acuity and
      complexity of patient disability and handicap is being measured and evaluated
      now. This article proposes the establishment of Rehabilitation Research
      Application Forums that would have the purpose of fostering dialogue regarding
      rehabilitation outcome research and its policy implications for the payer
      community. It also proposes the routine publication in industry journals of
      rehabilitation outcomes articles, accompanied by commentary written by
      individuals who are appointees to the Forum. The purpose would be more rapid and
      appropriate application of rehabilitation outcomes research.

PMID- 9270488
TI  - Drug delivery to the brain.

PMID- 9270489
TI  - Optimization of noninvasive activation studies with 15O-water and three
      dimensional positron emission tomography.
AB  - We investigated the effects of varying the injected dose, speed of injection, and
      scan duration to maximize the sensitivity of noninvasive activation studies with
      15O-water and three-dimensional positron emission tomography. A covert word
      generation task was used in four subjects with bolus injections of 2.5 to 3D mCi
      of 15O-water. The noise equivalent counts (NEC) for the whole brain peaked at an
      injected dose of 12 to 15 mCi. This was lower than expected from phantom studies,
      presumably because of the effect of radioactivity outside of the brain. A 10 mCi
      injection gave an NEC of 92.4 +/- 2.2% of the peak value. As the scan duration
      increased from 60 to 90 to 120 seconds, the areas of activation decreased in size
      or were no longer detected. Therefore, we selected a 1 minute scan using 10 mCi
      for bolus injections. We then performed simulation studies to evaluate, for a
      given CBF change, the effect on signal-to-noise ratio (S/N) of longer scan
      duration with slow tracer infusions. Using a measured arterial input function
      from a bolus injection, new input functions for longer duration injections and
      the corresponding tissue data were simulated. Combining information about image
      noise derived from Hoffman brain phantom studies with the simulated tissue data
      allowed calculation of the S/N for a given CBF change. The simulation shows that
      a slow infusion permits longer scan acquisitions with only a small loss in S/N.
      This allows the investigator to choose the injection duration, and thus the time
      period during which scan values are sensitive to regional CBF.

PMID- 9270490
TI  - Herpes simplex viral vectors expressing Bcl-2 are neuroprotective when delivered
      after a stroke.
AB  - Considerable interest has focused on the possibility of using viral vectors to
      deliver genes to the central nervous system for the purpose of decreasing
      necrotic neuronal injury. To that end, we have previously shown that a herpes
      simplex virus (HSV) vector expressing Bcl-2 could protect neurons from ischemia.
      In that study, vector was delivered before the ischemia. However, for such gene
      therapy to be of clinical use, vectors must be protective even if delivered after
      the onset of the insult. In the present study, we show that an HSV vector
      expressing Bcl-2 protects striatal neurons when delivered after focal ischemia.
      Rats were exposed to middle cerebral artery occlusion for 1 hour, followed by
      reperfusion, and damage was assessed 48 hours later. Delivery of the Bcl-2 vector
      30 minutes after reperfusion (i.e., 1.5 hours after ischemia onset) prevented any
      significant loss of virally-targeted neurons in the striatum. In contrast, in
      rats microinfused with a vector only expressing a reporter gene, a highly
      significant loss of neurons occurred. By 4 hours into the reperfusion period (5
      hours after ischemia onset), delivery of the Bcl-2 vector was no longer
      protective. These data show the efficacy of postinsult gene therapy strategies
      for the brain, underline the finite length of this temporal therapeutic window,
      and support the growing evidence attesting to the neuroprotective potential of
      Bcl-2.

PMID- 9270492
TI  - Apolipoprotein E-deficient mice have increased susceptibility to focal cerebral
      ischemia.
AB  - Recent evidence suggests that apolipoprotein E (ApoE) plays a role in neurologic
      disease. This experiment compared the neurologic and histologic outcome of ApoE
      deficient mutant and wild-type mice subjected to a 60- or 90-minute episode of
      middle cerebral artery filament occlusion and a recovery interval of 24 hours.
      With 60 minutes of ischemia, there was no mortality. Apolipoprotein E-deficient
      mice had larger infarcts (cortex: ApoE deficient = 20 mm3 +/- 12, wild-type = 9
      +/- 7 mm3, P = 0.03; subcortex: ApoE deficient = 22 +/- 7 mm3, wild-type = 16 +/-
      7 mm3, P = 0.07). Hemiparesis was less severe in wild-type animals (P = 0.02).
      After 90 minutes of ischemia, mortality in ApoE-deficient mice (n = 10) was 40%
      versus 0% in wild-type mice (n = 10; P = 0.09). Intraparenchymal hemorrhage was
      found in 3 of the 4 dead mice. No difference in cortical (ApoE deficient = 37 +/-
      8 mm3; wild-type = 31 +/- 18 mm3; P = 0.49) or subcortical (ApoE deficient = 30
      +/- 11 mm3; wild-type = 32 +/- 18 mm3; P = 0.78) infarct volumes was present
      among survivors. ApoE-deficient mice had a prolonged activated partial
      thromboplastin time and increased fibrinogen concentration. This data supports
      the hypothesis that apolipoprotein E plays a role in the pathophysiology of
      ischemic brain damage.

PMID- 9270491
TI  - Expression of growth inhibitory factor mRNA after focal ischemia in rat brain.
AB  - Growth inhibitory factor (GIF) is a small protein belonging to the
      metallothionein family that has the capacity to inhibit neuronal survival and
      neurite formation in vitro. This study was conducted to investigate the role of
      GIF in the brain afflicted with ischemic injury. We used the in situ
      hybridization technique and Northern blot analysis to study the changes in GIF
      messenger RNA (mRNA) expression in a rat focal ischemia model. On the first day,
      the expression tended to decrease in the hemisphere ipsilateral to the injury. It
      returned to normal levels on the second day except for the central area of the
      middle cerebral artery (MCA) territory. On the third and fourth day, the
      expression increased diffusely in the hemisphere of the affected side, including
      the subcortical area. Two weeks after ischemia, the GIF mRNA expression increased
      again but only in the peri-infarcted area. Down-regulation of GIF on the first
      day in the cortex ipsilateral to the infarction might promote neurite sprouting.
      The subsequent increase in GIF mRNA expression on the third and fourth day might
      be a symptom of neurons attempting to inhibit excessive neurite outgrowth, or to
      protect themselves against toxicity caused by oxygen radicals. The later increase
      in the limited area around the infarction may be related to astroglial reaction.
      Growth inhibitory factor may play an important role in regulating the central
      nervous system after ischemic insults.

PMID- 9270494
TI  - NGFI-B, c-fos, and c-jun mRNA expression in mouse brain after acute carbon
      monoxide intoxication.
AB  - The expression of immediate early genes (IEG) has been documented in the brain
      after various kinds of insults such as ischemia and hypoxia. To determine whether
      acute carbon monoxide intoxication (ACOI) might trigger IEG expression, adult ddY
      mice were subjected to carbon monoxide exposure at a rate of 30 mL/min for 35
      seconds. The levels of NGFI-B, c-fos, and c-jun mRNA were determined by Northern
      blot analysis. A time-course study in the cerebral cortex indicated that the
      induction of NGFI-B, c-fos, and c-jun mRNA started as early as 15 minutes,
      reached a peak at 30 minutes, and returned to the basal level at 1 hour after the
      ACOI. In addition, the temporal feature of the induction of these IEG mRNA in the
      hippocampus was very similar to that in the cerebral cortex. Examination of brain
      regions at 30 minutes after the ACOI revealed a significant induction of NGFI-B
      mRNA in the cerebellum, thalamus-hypothalamus, brainstem. as well as in the
      cortex and hippocampus, but not in the striatum or olfactory bulb. Furthermore,
      the neuroanatomical distribution of c-fos mRNA at 30 minutes after the ACOI was
      very similar to that of the NGFI-B mRNA. The widespread distribution of these IEG
      in the brain, especially in the cerebellum and brainstem, indicates that the
      major cause for the triggering of IEG expression in the brain by the ACOI might
      be a diffuse hypoxia. These findings show for the first time the temporal and
      spatial expression of IEG in the brain after ACOI.

PMID- 9270493
TI  - Hypoxic-ischemic injury induces monocyte chemoattractant protein-1 expression in
      neonatal rat brain.
AB  - Monocyte chemoattractant protein-1 (MCP-1) regulates monocyte accumulation in
      several macrophage-dependent experimental disease models. In the neonatal brain,
      activated microglia accumulate rapidly after hypoxic-ischemic injury. These cells
      produce potentially neurotoxic factors that may contribute to the progression of
      injury. To determine whether MCP-1 could be one of the molecular signals that
      influences the microglial response to hypoxic-ischemic injury in the neonatal
      brain, we examined the impact of acute hypoxic-ischemic injury on MCP-1 mRNA and
      protein expression. Seven-day-old rats underwent right carotid artery ligation,
      followed by 3 hours of 8% oxygen exposure, to elicit ipsilateral forebrain
      hypoxic-ischemic injury. To detect MCP-1 mRNA in situ hybridization assays were
      performed using 35S-labeled antisense riboprobes generated from rat MCP-1 cDNA.
      Animals were evaluated 0, 1, 2, 4, 8, 16, 24, 48, and 120 hours after hypoxic
      exposure (N > or = 3/group). Immunocytochemistry (with a polyclonal rabbit
      antirat MCP-1 antibody) was used to determine the anatomic and temporal
      distribution of MCP-1, in samples obtained 10 minutes to 5 days after hypoxic
      exposure (N > or = 3/group). Monocyte chemoattractant protein-1 mRNA was first
      detected in periventricular regions of the lesioned hemisphere 1 hour after
      hypoxia-ischemia; periependymal and intraparenchymal MCP-1 mRNA expression were
      detected at 4 hours; hybridization signal peaked at 8 to 24 hours; and no MCP-1
      mRNA was detected at 48 and 120 hours. In lesioned forebrain, MCP-1 protein
      expression were consistently detected at 2.5 to 48 hours after hypoxia-ischemia.
      Many immunoreactive cells appeared to be neurons. These results suggest that in
      the developing brain, MCP-1 could represent a functionally important molecular
      signal for the microglial response to hypoxic-ischemic injury.

PMID- 9270495
TI  - Cortical application of potassium chloride induces the low-molecular weight heat
      shock protein (Hsp27) in astrocytes.
AB  - Spreading depression induces tolerance to ischemic injury, and ischemic tolerance
      has been associated with expression of heat shock proteins (Hsp). Here we examine
      Hsp27 expression after KCl-induced spreading depression. Twenty-minute cortical
      KCl application induced Hsp27 immunoreactivity in glial fibrillary acidic protein
      positive astrocytes of the ipsilateral neocortex. Systemic administration of MK
      801 (3 mg/kg) suppressed KCl-induced Hsp27 expression in the parietal cortex.
      Astrocytes in the posterior cingulate and retrosplenial cortex did not express
      Hsp27 after KCl application but did express Hsp27 after systemic administration
      of high dose MK-801 (9 mg/kg). Whereas Hsp27 was usually observed in all layers
      of the parietal cortex after 5-minute application of KCl, in 2 of 6 rats, Hsp27
      was seen in clusters of astrocytes or in astrocytes in the superficial layers I
      to III of the parietal cortex. We conclude that (1) cortical application of KCl
      triggered Hsp27 astrocytic expression; (2) astrocytes in the cingulate and
      retrosplenial cortex responded differently compared with astrocytes of the
      parietal cortex; (3) Hsp27 expression progressed from small clusters of
      astrocytes throughout superficial layers of the cortex that joined and recruited
      astrocytes in deeper layers; (4) several mechanisms induced Hsp27 astrocytic
      expression. We propose that Hsp27 is involved in spreading depression-induced
      ischemic tolerance through protection of astrocyte function.

PMID- 9270497
TI  - Cerebral angiogenesis triggered by severe chronic hypoxia displays regional
      differences.
AB  - The blood vessels in the brains of adult rats subjected to chronic normobaric
      hypoxia and control animals housed under normoxic conditions were
      morphometrically studied. Hypoxic male inbred Wistar rats were exposed over a
      period of 130 days to decreasing amounts of oxygen starting from 21% down to 7%
      (15%: 15 days; 12%, 10%, 8%: 22 days, respectively; 7%: 49 days). Areas of
      cerebral cortex, striatum, hippocampus, cerebellum, and medulla oblongata were
      investigated. The ratio vessel number per mm2 tissue and the average vessel size
      were measured using a Quantimet Q570. In the hypoxic animals, cerebral cortex,
      striatum, and hippocampus showed a significant increase of the vessel density per
      mm2 tissue (P < 0.01 or P < 0.05). The differences in both groups were highest in
      the striatum and hippocampus. In the cerebellum and the medulla oblongata of
      hypoxic animals, only a tendency to higher vessel numbers per mm2 tissue was
      found. The average blood vessel size differed only in the cerebral cortex and the
      cerebellum, but not in the other brain regions tested. The results indicate that
      the adaptation of the brain circulation to hypoxia is achieved by both
      angiogenesis and dilatation of microvessels, and that the pattern of the
      microcirculatory changes is not homogenous in all regions.

PMID- 9270496
TI  - NG-nitro-L-arginine methyl ester modifies the input function measured by dynamic
      susceptibility contrast magnetic resonance imaging.
AB  - In rat brain dynamic susceptibility contrast magnetic resonance (MR) images,
      vessels visible on the same scan plane as the brain tissue were used to measure
      the characteristics of the input function of the MR contrast agent gadopentetate
      dimeglumine. MR images were acquired 30 and 60 minutes after intravenous
      injections of 3 mg/kg and 15 mg/kg NG-Nitro-L-arginine methyl ester (L-NAME) (n =
      9). The time of arrival (TOA) and the mean transit time corrected for TOA of the
      input function were increased by 3 mg/kg or 15 mg/kg L-NAME. The area of the
      input function was increased by 15 mg/kg L-NAME. In two animals, similar
      modifications of the input function induced by 20 mg/kg L-NAME were reversed by
      infusion of sodium nitroprusside. In two other animals, MABP was increased by
      phenylephrine to a similar extent as in L-NAME experiments, but did not induce
      the same modifications of the input function, showing that the action of L-NAME
      on the input function was not simply caused by an effect on MABP. These results
      show that the input function can be significantly altered by manipulations widely
      used in cerebrovascular studies. These input function changes have important
      implications for calculation of cerebral blood flow.

PMID- 9270498
TI  - Hypoxia-induced inhibition of the response to nitroxidergic nerve stimulation in
      canine cerebral arteries.
AB  - In isolated canine middle cerebral arteries contracted with prostaglandin F2
      alpha, transmural electrical stimulation (TES), nicotine, and substance P
      produced relaxations. Transmural electrical stimulation- and nicotine-induced
      endothelium-independent responses are mediated by nitric oxide (NO) liberated
      from perivascular nerve, whereas substance P-induced relaxations are mediated by
      endothelium-derived NO. These responses were attenuated by replacement of 95% O2
      and 5% CO2 gas (about 550 mm Hg of partial O2 pressure) with 95% N2 and 5% CO2
      gas (about 40 mm Hg); inhibition of the response to TES was stabilized 30 minutes
      later. Reoxygenation partially reversed the response. Relaxations caused by
      exogenous NO were not influenced by hypoxia. Inhibition by hypoxia of the
      response to TES was not affected by superoxide dismutase. However, the inhibitory
      effect was prevented by amiloride and dimethyl-amiloride, Na(+)-H+ exchange
      inhibitors, or acidosis caused by the addition of HCl. The inhibition by hypoxia
      was reversed by amiloride. It is concluded that depression by hypoxia of the
      response mediated by endogenous NO is associated with impaired membrane function
      caused by restoration of normal intracellular pH by Na(+)-H+ exchanger.

PMID- 9270499
TI  - Antimicrobial agents for the dermatologist. I. Beta-lactam antibiotics and
      related compounds.
AB  - We review the newer antimicrobial agents that are being employed by
      dermatologists with increased frequency as well as some of the more commonly used
      older agents. Particular emphasis is based on selection factors such as causative
      pathogens and their resistance profiles, routes of administration, toxicity, drug
      interactions, and dosing requirements. Emphasis in this review is on the newer
      classes of antimicrobials such as third- and fourth-generation cephalosporins;
      beta-lactam, beta-lactamase inhibitor combination agents; monobactams;
      carbapenems; macrolides; and fluoroquinolones. Dermatologic indications and
      treatment alternatives are highlighted; this will expand the practicing
      clinician's therapeutic armamentarium and enable him/her to make rational
      decisions concerning treatment approaches to infectious disease problems
      encountered in daily practice.

PMID- 9270500
TI  - Proliferation marker Ki-S5 as a diagnostic tool in melanocytic lesions.
AB  - BACKGROUND: A discrimination between benign and malignant melanocytic lesions is
      not always possible by conventional histology. OBJECTIVE: Our purpose was to
      determine the proliferative activity in various types of melanocytic neoplasms
      and to appraise its value as a diagnostic adjunct. METHODS: The growth fraction
      was assessed immunohistochemically in 398 melanocytic lesions by means of the
      monoclonal antibody Ki-S5 directed to the Ki-67 antigen. In this way, a cut-off
      level was defined and applied to 112 lesions of equivocal histology. The revised
      diagnoses were correlated to the clinical courses. RESULTS: Common nevi, Spitz
      nevi, and melanomas exhibited significantly different proliferation indices and
      distinctive distribution patterns of cycling cells. In agreement, malignancy
      diagnosed on the basis of a growth fraction greater than 5% was confirmed by
      disease progression in 68% of our cases with uncertain diagnosis. CONCLUSION:
      Determination of the proliferative activity in melanocytic lesions may usefully
      complement conventional histology to improve diagnostic accuracy.

PMID- 9270501
TI  - Trends in sun exposure knowledge, attitudes, and behaviors: 1986 to 1996.
AB  - BACKGROUND: The American Academy of Dermatology's national program Melanoma/Skin
      Cancer Detection and Prevention, developed in response to the rising incidence of
      invasive melanoma in the United States, has annually during the past decade
      produced extensive print, radio, and television coverage about the dangers of sun
      exposure and benefits of sun protection. OBJECTIVE: We measured the progress
      achieved in increasing the awareness and knowledge of skin cancer and changing
      the attitudes, beliefs, and behaviors that affect skin cancer risk. We also
      describe current sun-related behavior including sunburning, assess the likelihood
      of practicing sun protection strategies, and provide a baseline against which
      future changes in sun protection behavior may be evaluated. METHODS: A 1996
      telephone survey repeated questions used in 1986 to evaluate change and used
      classifying questions to better define attitudes and behaviors. RESULTS: From
      1986 to 1996, the knowledge of the perceived harmful effects of the sun
      significantly broadened, but the UV exposure behavior as measured by sunburning
      (30% to 39%) and regular use of a tanning booth (2% to 6%) also increased. There
      was a decline in the attitude that having a tan was healthy; however, in 1996
      having a tan was still considered to enhance appearance, particularly by men.
      Sunscreen use increased (35% to 53%). Women, younger persons, persons residing in
      areas with fewer sunny days, and whites were more likely to tan intentionally,
      but men who lived in the South were more likely to sunburn. CONCLUSION: During
      the past decade, the early process of change involving cognitive and emotional
      activities began. With this study, high-risk population subsets performing
      specific adverse behavior were identified. In the future, they can be targeted
      with messages that promote attitudinal and behavioral change.

PMID- 9270502
TI  - Immunosuppression induced by acute solar-simulated ultraviolet exposure in
      humans: prevention by a sunscreen with a sun protection factor of 15 and high UVA
      protection.
AB  - BACKGROUND: Cutaneous exposure to UVB radiation impairs the induction of contact
      hypersensitivity (CHS). Variable results have been found among studies examining
      the use of sunscreens to prevent UV-induced immunosuppression. OBJECTIVE: Our
      purpose was to determine whether solar-simulated exposure of human skin resulted
      in an impairment of CHS responses and whether the preapplication of an
      intermediate sun protection factor (SPF) sunscreen could prevent this locally UV
      induced immunosuppression. METHODS: Irritant and CHS responses to
      dinitrochlorobenzene (DNCB) were randomly assessed in 160 human volunteers with
      or without UV exposure and with or without prior application of an SPF 15
      sunscreen with high UVA protection. DNCB sensitization was performed 3 days after
      acute UV irradiation corresponding to 3 minimal erythema doses. RESULTS: After
      solar-simulated UV exposure, the percentage of positive responses to DNCB
      sensitization dropped from 95% to 50% (p = 0.003). Prior application of the
      sunscreen formulation did not modify the percentage of positive responses (90%)
      and maintained the immunization rate at 85% among volunteers exposed to UV.
      CONCLUSION: A localized sunburn can impair the afferent arm of CHS reactions in
      humans. The use of intermediate SPF sunscreens with high UVA protection
      adequately protects from the suppression of CHS responses that occurs after acute
      solar-simulated UV exposure.

PMID- 9270503
TI  - Resolution requirements for digital images in dermatology.
AB  - BACKGROUND: The digital image has become an important tool in dermatology because
      of the rapid development of computer hardware, networks, and the World Wide Web.
      OBJECTIVE: Our purpose was to examine the resolution requirements for digital
      images. METHODS: Slides of eight selected images showing characteristic lesions
      were produced in five different resolutions each, ranging from 192 x 128 x 24
      (192 pixels x, 128 pixels y, and 24-bit color depth) up to 3072 x 2048 x 24. They
      were compared side by side by a group of six experienced dermatologists using a
      standardized questionnaire. RESULTS: Images at the resolution of 768 x 512 x 24
      were perceived as equivalent to higher resolutions, whereas a clear difference
      was visible between 768 x 512 x 24 and 384 x 256 x 24. The slide projector had a
      significant influence on the rating of the images. CONCLUSION: For digital images
      in dermatology a resolution of 768 x 512 x 24 is suitable to recognize the
      relevant details of the source image.

PMID- 9270504
TI  - Cutaneous manifestations of Churg-Strauss syndrome: a clinicopathologic
      correlation.
AB  - BACKGROUND: Allergic granulomatosis of Churg-Strauss (Churg-Strauss syndrome) is
      a distinct clinical disease of multisystem vasculitis. OBJECTIVE: We characterize
      the clinical and histologic features of cutaneous findings in Churg-Strauss
      syndrome. METHODS: All patients with Churg-Strauss syndrome seen between 1976 and
      1995 were retrospectively reviewed. RESULTS: Ninety patients with the diagnosis
      of Churg-Strauss syndrome were identified; 36 (40%) had cutaneous findings. Five
      patients (6%) had skin lesions as the initial manifestation. The most frequent
      cutaneous findings were purpura and petechiae on the lower extremities and
      cutaneous nodules and papules on the elbows. In 37 biopsy specimens from 29
      patients, the most common findings were extravascular necrotizing granuloma (15
      specimens) and leukocytoclastic vasculitis (16 specimens). CONCLUSION: Cutaneous
      lesions in Churg-Strauss syndrome are common. Their characteristic clinical and
      histologic pattern may help establish the diagnosis.

PMID- 9270505
TI  - Depth of morphologic skin damage and viability after one, two, and three passes
      of a high-energy, short-pulse CO2 laser (Tru-Pulse) in pig skin.
AB  - BACKGROUND: CO2 laser energy is absorbed by water, which is present in all
      tissue. The depth of penetration of CO2 lasers is narrow with minimal reflection,
      scatter, or transmission. However, thermal damage has limited the usefulness of
      conventional, continuous-wave CO2 lasers for debridement as demonstrated by wound
      healing studies. The development of high-energy CO2 lasers, with pulse durations
      that are less than the thermal relaxation time of tissue, have made vaporization
      of skin for resurfacing and wound debridement possible because of the decreased
      risk of thermal damage. OBJECTIVE: This study was performed to evaluate thermal
      damage produced by a CO2 laser. METHODS: Routine histopathologic examination and
      nitroblue-tetrazolium chloride (NBTC) staining were used to evaluate the depth of
      tissue damage and viability in weanling pig skin after one, two, and three passes
      of the laser. RESULTS: At a pulse energy of 300 mJ, with a pulse duration of 60
      microseconds, one pass of the laser produced vaporization of the epidermis with
      minimal thermal damage. Two passes produced areas of denatured collagen with loss
      of viable cells in the superficial papillary dermis. Three passes extended the
      damage into the papillary dermis. CONCLUSION: Hyalinization of collagen appears
      to correspond well with the level of thermal damage as measured by NBTC staining.
      Our findings suggest that the energy necessary to vaporize the dermis may be
      greater than that needed to vaporize epidermis.

PMID- 9270506
TI  - Sensitivity of indirect immunofluorescence, substrate specificity, and
      immunoblotting in the diagnosis of pemphigus.
AB  - BACKGROUND: Several assays are available to detect pemphigus antibodies. The most
      commonly used are indirect immunofluorescence (IIF) and immunoblotting (IB).
      OBJECTIVE: Our purpose was to compare the sensitivity of these assays in
      detecting pemphigus antibodies. METHODS: Fifty-two sera from 41 patients with
      pemphigus vulgaris (PV) and 22 sera from 18 patients with pemphigus foliaceus
      (PF) were tested concurrently for the presence of pemphigus antibodies. The IIF
      studies were conducted with two different substrates: monkey and guinea pig
      esophagus. RESULTS: Pemphigus antibodies were detected with equal sensitivity by
      IIF in patients with PV and PF (i.e., positive in 87% and 86% of sera,
      respectively). By contrast, IB assay was much less sensitive in PF than in PV
      (i.e., positive in 45% vs 83% of sera, respectively). The antibodies in PV
      generally reacted more strongly against monkey esophagus, whereas those in PF
      reacted more strongly against guinea pig esophagus. All patients with
      intercellular antibodies that reacted more strongly against monkey than guinea
      pig esophagus had PV, whereas all those with intercellular antibodies that
      reacted more strongly against guinea pig than monkey esophagus had PF.
      CONCLUSION: IIF is a more sensitive assay than IB for detecting antibodies
      associated with PF. The substrate specificity of the antibodies provides a simple
      means to distinguish between PV and PF.

PMID- 9270507
TI  - Tretinoin emollient cream for photodamaged skin: results of 48-week, multicenter,
      double-blind studies.
AB  - BACKGROUND: The ability of topical tretinoin to improve certain signs of skin
      photodamage has been shown previously. OBJECTIVE: Our purpose was to assess the
      effectiveness of tretinoin emollient cream in maintaining or further improving
      photodamaged skin during extended use. METHODS: Photodamaged subjects who
      completed 24 weeks of once-daily use of tretinoin emollient cream 0.05% (n = 149)
      or 0.01% (n = 149) continued to use the same strength formulation in a 24-week
      double-blind extension. RESULTS: Maintenance of improvement or continued
      reduction in signs of photodamage was noted in both investigators' and subjects'
      evaluations of the 0.05% and 0.01% preparations; these results were confirmed by
      skin replica analyses. Cutaneous side effects were less common during the
      extension study than during the first 24 weeks of therapy. CONCLUSION: Both
      strengths of tretinoin emollient cream (0.05% and 0.01%) appeared safe and
      effective in the treatment of photodamaged skin during a 48-week treatment
      period.

PMID- 9270509
TI  - A randomized trial to assess once-daily topical treatment of tinea corporis with
      butenafine, a new antifungal agent.
AB  - BACKGROUND: Tinea corporis treatment usually requires topical application of an
      antifungal agent for 2 to 3 weeks. OBJECTIVE: We evaluated short-term treatment
      of tinea corporis with butenafine hydrochloride, a new benzylamine with in vitro
      fungicidal activity. METHODS: Patients (n = 78) were randomly selected to apply
      butenafine or its cream vehicle alone once daily for 14 days and were
      periodically assessed until day 42. RESULTS: Butenafine recipients had
      significantly higher rates of mycologic cure beginning at day 7 (64% vs 9%) with
      continued improvements through day 42 (88% vs 17%). They also had higher rates of
      effective treatment (mycologic cure and 90% to 100% symptom improvement) at day 7
      (33% vs 0%) with increasing rates through day 42 (81% vs 14%). CONCLUSION:
      Butenafine provides rapid and persistent antifungal activity and symptom relief
      in patients with tinea corporis. Significant effects were observed within 7 days
      of therapy initiation, and increasing effectiveness was observed 4 weeks after
      therapy.

PMID- 9270508
TI  - Sustained improvement in photodamaged skin with reduced tretinoin emollient cream
      treatment regimen: effect of once-weekly and three-times-weekly applications.
AB  - BACKGROUND: Previous studies have documented reversal of long-term photodamage
      with once-daily applications of topical tretinoin. OBJECTIVE: Our purpose was to
      assess the effectiveness of tretinoin emollient cream in maintaining improvement
      in photodamage with a reduced frequency of applications. METHODS: A total of 126
      subjects who completed 48 weeks of once-daily treatment with tretinoin emollient
      cream 0.05% were enrolled for an additional 24 weeks of tretinoin once weekly,
      three times weekly, or no therapy. RESULTS: The clinical improvement observed
      during 48 weeks of once-daily treatment was sustained with three-times weekly
      applications and to a lesser extent with once-weekly dosing, whereas effects
      tended to regress in subjects off therapy. The overall incidence of adverse
      events in the skin and subcutaneous tissues appeared to vary with dose frequency.
      CONCLUSION: After 48 weeks of once-daily treatment, the continued use of
      tretinoin emollient cream 0.05% at a dose of three times per week maintains and,
      in some cases, may further enhance improvement in photodamage. Discontinuation of
      therapy results in some reversal of beneficial effects.

PMID- 9270510
TI  - Mohs micrographic surgery for the treatment of primary cutaneous melanoma.
AB  - BACKGROUND: Mohs micrographic surgery is thought to be a useful therapy for
      cutaneous melanoma. Controversy persists, however, because there are few
      published reports that document its safety and efficacy. OBJECTIVE: Our purpose
      was to determine the safety and efficacy of Mohs micrographic surgery for the
      treatment of cutaneous melanoma. METHODS: A consecutive sample of 535 patients
      referred for treatment of 553 primary cutaneous melanomas was entered into the
      study. Of this sample, 99.5% of patients completed their first 5 years of follow
      up. All melanomas were excised by means of fresh-tissue Mohs micrographic surgery
      with frozen-section examination of the margin. The 5-year Kaplan-Meier melanoma
      mortality, metastasis, and local recurrence rates were compared with historical
      control cases. RESULTS: Mohs micrographic surgery provided 5-year survival and
      metastatic rates equivalent to or better than historical controls that were
      treated by standard wide-margin surgery. Satellite metastases were not more
      common with the narrow margins used with Mohs micrographic surgery. Local
      recurrences from inadequate excision of the primary tumor were infrequent (0.5%).
      The majority of melanomas were successfully excised with a narrow margin (83%
      were excised with a 6 mm margin). CONCLUSION: Mohs micrographic surgery is an
      effective therapy for primary cutaneous melanoma. It may be particularly useful
      to conserve tissue for melanomas on the head, neck, hands, or feet or for
      melanomas with indistinct clinical margins.

PMID- 9270511
TI  - Biopsy specimen findings in patients with previous lower extremity cellulitis
      after saphenous venectomy for coronary artery bypass graft surgery.
AB  - BACKGROUND: No previous study has examined the immune and inflammatory mechanisms
      involved in the pathogenesis of lower extremity cellulitis after saphenous
      venectomy for coronary artery bypass graft surgery. OBJECTIVE: Our purpose was to
      determine the histopathologic, immunologic, and inflammatory findings in skin
      biopsy specimens from saphenous venectomy limbs of patients with previous bouts
      of cellulitis. METHODS: Biopsy specimens were obtained from five patients with
      previous episodes of cellulitis. Specimens of the contralateral lower extremity
      of each patient were obtained for controlled comparisons. RESULTS:
      Histopathologic findings did not provide evidence that could account for the
      tendency for cellulitis to develop. Moreover, the distribution of CD1a, HLA-DR,
      intercellular adhesion molecule-1, and lymphocyte function-associated antigen
      type 1 were similar in specimens from the postvenectomy and contralateral legs.
      No tumor necrosis factor-alpha expression was found in specimens from the lower
      extremities. CONCLUSION: The mechanisms responsible for the production of this
      disorder do not involve the mediators studied.

PMID- 9270513
TI  - Surgical pearl: modified rhombic flap.

PMID- 9270512
TI  - Electrosurgery and cardiac devices.
AB  - The increased number of patients with implantable cardiac devices presents a
      unique challenge to physicians performing office-based electrosurgical
      procedures. Electrosurgery can be performed safely if the electrosurgical
      techniques and potential risks from these devices are understood. We present an
      overview of the most common types of implantable cardiac devices, potential
      complications associated with them, and recommendations for preoperative
      evaluation, intraoperative monitoring, and postoperative follow-up.

PMID- 9270514
TI  - Eosinophilic pustular folliculitis (Ofuji's disease).

PMID- 9270515
TI  - Keratosis lichenoides chronica: response to topical calcipotriol.

PMID- 9270516
TI  - Bullous eruption in a patient with systemic lupus erythematosus: mite dermatitis
      caused by Cheyletiella blakei.

PMID- 9270517
TI  - Multiple pilomatricomas in association with myotonic dystrophy and a family
      history of melanoma.

PMID- 9270518
TI  - Cutaneous Paecilomyces lilacinus infection: report of two novel cases.

PMID- 9270519
TI  - Randomized single-blind study of efficacy and tolerability of terbinafine in the
      treatment of tinea capitis.

PMID- 9270520
TI  - Fluconazole for the treatment of tinea capitis in children.

PMID- 9270521
TI  - Analysis of HLA antigens in Caucasian patients with acute febrile neutrophilic
      dermatosis (Sweet's syndrome).

PMID- 9270522
TI  - Effect of topical pramoxine on experimentally induced pruritus in humans.

PMID- 9270523
TI  - Erythromelalgia: response to serotonin reuptake inhibitors.

PMID- 9270524
TI  - The laptop computer in dermatology.

PMID- 9270525
TI  - Lymphomatoid papulosis, pityriasis lichenoides et varioliformis acuta, and
      anaplastic large-cell (Ki-1+) lymphoma.

PMID- 9270526
TI  - Response rates in photopheresis therapy for cutaneous T-cell lymphoma.

PMID- 9270528
TI  - Cimetidine therapy for warts in children.

PMID- 9270529
TI  - Superciliary upsweep or tented eyebrows. A distinct mendelian trait.
AB  - Facial appearance is influenced by the anatomic relationship of the eyebrows and
      eyelids. Anatomic variants may characterize members of a pedigree and thus
      constitute a family mark. We studied three white families with circumscribed
      upward slanting eyebrows. In one pedigree the family mark was inherited over four
      generations, suggesting an autosomal dominant inheritance. In the other two
      families the eyebrow variation was documented in three members over two
      generations, compatible with an autosomal dominant mode of transmission. In two
      families the expression of the trait varied in the form of both bilateral and
      unilateral involvement. No diseases or malformations were associated with this
      eyebrow anomaly.

PMID- 9270527
TI  - Treatment of psoriasis with the pulsed dye laser.

PMID- 9270531
TI  - Necrosing livedo reticularis in a patient with recurrent pulmonary hemorrhage.
AB  - The antiphospholipid antibody (APS) syndrome is characterized by antiphospholipid
      antibodies (lupus anticoagulant [LA] or anticardiolipin [aCL], a recurrent
      arterial and venous thrombosis, recurrent fetal loss, and thrombocytopenia.
      Pulmonary hemorrhage is an unusual complication. We describe a 32-year-old woman
      with a history of recurrent pulmonary hemorrhage and transient renal dysfunction.
      Her original diagnosis was Goodpasture's syndrome, and she was treated with
      immunosuppressive drugs. Necrosing livedo reticularis of the legs subsequently
      developed. The presence of aCL and LA in the patient's serum, the finding of
      noninflammatory microthrombi in the dermal capillaries, and the lack of
      laboratory or pathologic features of Goodpasture's syndrome, confirmed a
      diagnosis of APS in this patient.

PMID- 9270532
TI  - An ulcerated lesion at the BCG vaccination site during the course of Kawasaki
      disease.
AB  - We describe a bacillus Calmette-Guerin (BCG) granuloma that occurred during the
      course of Kawasaki disease. A 12-month-old male infant with Kawasaki disease had
      an erythematous indurated plaque with prominent necrotic ulceration at the BCG
      vaccination site on the left upper arm. Histologic study showed a granulomatous
      reaction consisting of epithelioid histiocytes, lymphoid cells, and Langhans-type
      giant cells. No evidence of mycobacterial infection was obtained. The lesion
      healed completely within 2 weeks without administration of antituberculous
      agents. We believe that the granulomatous reaction occurred as a result of
      hypersensitivity to proteins in the BCG vaccine, which appeared after the onset
      of Kawasaki disease.

PMID- 9270530
TI  - Atenolol-induced lupus erythematosus.
AB  - Atenolol is a beta-blocker commonly used for treating hypertension. It can induce
      various kinds of adverse side effects, including psoriasiform skin eruptions,
      skin necrosis, vasculitis, and (rarely) drug-induced connective tissue disease.
      We encountered a patient receiving atenolol for his hypertension for 3 years who
      subsequently acquired connective tissue disease and antihistone antibodies. The
      initial serologic antinuclear antibody test was negative at a dilution of 1/20
      but was positive after further serial dilutions, indicating the prozone
      phenomenon as the cause of the false-negative result. Six months after
      discontinuation of atenolol, the skin rash disappeared and antihistone antibody
      subsided. His skin rash reappeared on rechallenge with atenolol for 3 days,
      confirming that atenolol was responsible for his lupus erythematosus.

PMID- 9270533
TI  - Alkaptonuric ochronosis: report of two affected brothers.
AB  - Alkaptonuric ochronosis is a rare inborn metabolic disorder. Because of the
      deficient activity of the enzyme homogentisic acid oxidase, homogentisic acid
      accumulates in plasma, is deposited in various tissues and is excreted in large
      amounts in urine. Dark brown discoloration of urine on exposure to air or after
      addition of alkaline solution is characteristic. We describe two brothers with
      typical alkaptonuric ochronosis with dark urine, blue pigmentation of auricles
      and axillae, focal brown hyperpigmentation of sclerae, and anthropathy.

PMID- 9270534
TI  - Granulocytic sarcoma in the absence of myeloid leukemia.
AB  - Granulocytic sarcoma is an extramedullary tumor composed of immature granulocytic
      precursor cells. It usually occurs in association with leukemia or other
      myeloproliferative disorders but can occur without overt hematologic disease. We
      describe a 6-year-old boy with granulocytic sarcoma in the absence of
      demonstrable hematologic disease and review the literature regarding the
      diagnosis, clinical associations, and treatment of this condition.

PMID- 9270535
TI  - Mucinous nevus: report of two cases and review of the literature.
AB  - We report two cases of nervus mucinosis with papulonodules distributed
      dermatomally on the right T12 and L1 areas. Case 1 is a 61-year-old man who
      exhibited nodular lesions on the right abdomen in a zosteriform arrangement.
      Alcian blue staining showed the presence of mucin in the papillary dermis. Case 2
      is a 17-year-old man who had a 10-year history of match-head to bean-sized skin
      lesions, multiple papules, and nodules distributed dermatomally on the right
      lower back.

PMID- 9270536
TI  - Langerhans' cell histiocytosis in adults.
AB  - Three cases of Langerhans' cell histiocytosis with unusual clinical and
      histopathologic features are described. The first two cases illustrate diagnostic
      pitfalls that underscore the importance of considering Langerhans' cell
      histiocytosis in the differential diagnosis of purpuric papular eruptions of the
      scalp and intertriginous areas, particularly in association with hypothalamic,
      pituitary, or liver disease. The third case is the first report of Langerhans'
      cell histiocytosis presenting as a vesicular eruption.

PMID- 9270537
TI  - First report of mycetoma caused by Arthrographis kalrae: successful treatment
      with itraconazole.
AB  - We report the first case of eumycetoma of the hand caused by Arthrographis
      kalrae. Cure was obtained with a 4-month course of itraconazole.

PMID- 9270538
TI  - Generalized essential telangiectasia in the presence of gastrointestinal
      bleeding.
AB  - Generalized essential telangiectasia was well defined more than 30 years ago.
      There have been no reported cases of associated gastrointestinal (GI) bleeding.
      Recurrent hemorrhage in the setting of telangiectases, including GI bleeding, is
      more typically associated with hereditary hemorrhagic telangiectasia. We report a
      unique case of a woman with generalized essential telangiectasia and GI bleeding
      from a watermelon stomach. We include a brief review of the literature of
      watermelon stomach, generalized essential telangiectasia, and hereditary
      hemorrhagic telangiectasia.

PMID- 9270539
TI  - Plantar granulomatous cutaneous T-cell lymphoma.

PMID- 9270540
TI  - Penile verrucous carcinoma in a 37-year-old circumcised man.
AB  - Squamous cell carcinoma of the penis is almost exclusively a lesion of
      uncircumcised older men. It represents about 1% of cancers in men in the United
      States and 11% to 12% of all cancers in men in countries where circumcision is
      not routinely practiced. Verrucous carcinoma is an uncommon variant that accounts
      for only 5% to 16% of all penile squamous cell carcinomas. We describe penile
      verrucous carcinoma in a 37-year-old white man who had been circumcised in
      infancy. To our knowledge this is the first case report of verrucous carcinoma in
      a circumcised man without any predisposing penile anatomic abnormalities.

PMID- 9270541
TI  - Malignant melanoma and levodopa: is there a relationship? Two new cases and a
      review of the literature.
AB  - The incidence of malignant melanoma (MM) is rising. Besides UV radiation, other
      factors may contribute to this. We describe two patients in whom MM developed
      during treatment with levodopa. Levodopa has been implicated as an agent that
      could enhance the development of MM. However, review of the literature does not
      provide evidence of a definite relationship between treatment with levodopa and
      the development of MM. Despite this, it is suggested that patients treated with
      levodopa, particularly those with a history of MM, be observed carefully for
      changes in or development of new pigmented lesions.

PMID- 9270542
TI  - Eruptive melanocytic nevi after Stevens-Johnson syndrome.
AB  - Widespread melanocytic nevi may rarely appear suddenly after a severe bullous
      disease. We describe two patients in whom eruptive melanocytic nevi developed 3
      weeks after a severe episode of Stevens-Johnson syndrome. Benign melanocytic
      proliferation may develop after a bullous dermatosis and should not be confused
      with malignant or metastatic melanoma.

PMID- 9270543
TI  - Mucoepidermoid carcinoma with cutaneous presentation.
AB  - Mucoepidermoid carcinomas are malignant neoplasms that rarely involve the skin.
      Composed of both mucus-secreting cells and epidermoid-type cells in various
      proportions, mucoepidermoid carcinomas occur most commonly in salivary glands. In
      this case report, we describe a high-grade mucoepidermoid carcinoma with
      cutaneous involvement. Although this patient was referred for Mohs' micrographic
      surgery, further evaluation showed either direct or metastatic extension from the
      parotid gland to skin and distant metastases to the lung and bone. Despite
      extensive bone involvement, serum levels of ionized calcium, phosphorus, and
      lactate dehydrogenase remained normal. In view of the widespread metastases, the
      treatment plan was altered to radiotherapy and chemotherapy instead of surgery.
      Instructive lessons from this case include the recognition by dermatologists of
      this rare entity, the importance of a detailed history and complete evaluation of
      the patient before determining appropriate therapy, and the necessity of
      individualizing diagnostic tests to a particular patient.

PMID- 9270544
TI  - Trichoepithelioma with an adjacent basal cell carcinoma, transformation or
      collision?
AB  - Trichoepitheliomas (TEs) are benign follicular neoplasms that can be difficult to
      separate histologically from basal cell carcinomas (BCCs). It is important to
      make this distinction, because the treatments and prognoses differ for the two
      lesions. Previous reports have employed both histologic and immunohistochemical
      data in order to separate these two lesions. It is believed that transformation
      from a TE to a BCC is a rare event. We describe a case in which a single lesion
      with features of TE and BCC is present in a patient with multiple lesions of BCC.

PMID- 9270545
TI  - Periorbital edema as an initial presentation of rosacea.
AB  - Rosacea is a common dermatosis with a variety of clinical manifestations. The
      eyes are often affected. The most frequent ocular findings are blepharitis and
      conjunctivitis. We describe three patients with rosacea in whom periorbital edema
      was the initial presentation. This symptom may be confused with other dermatoses
      and may be refractory to conventional treatments for rosacea.

PMID- 9270546
TI  - Multiple idiopathic mucosal neuromas: a minor form of multiple endocrine
      neoplasia type 2B or a new entity?
AB  - Multiple endocrine neoplasia type 2B (MEN 2B) is a rare autosomal dominant
      process characterized by medullary thyroid carcinoma, pheochromocytoma, and
      mucosal neuromas. A point mutation at codon 918 of the RET protooncogene has been
      observed in approximately 90% of patients and families with MEN 2B. Mucosal
      neuromas are the most consistent and distinctive feature (100% of patients) of
      MEN 2B and are considered pathognomonic. We describe a 35-year-old woman with
      mucosal neuromas of the lower lip and tongue that appeared in early childhood.
      Examination did not reveal other abnormalities. After a follow-up of more than 22
      years with periodic clinical, biochemical, and radiologic studies, no evidence of
      MEN 2B has been detected. Analysis of the RET protooncogene exons 10, 11, and 16
      did not demonstrate point mutation in the MEN 2B region (M918T).

PMID- 9270547
TI  - Multiple eruptive milia: report of a case, review of the literature, and a
      classification.
AB  - A 71-year-old man presented with an acute onset of multiple white papules on the
      face and chest. Histologic sections demonstrated multiple milia. The rare
      condition of multiple eruptive milia occurs when crops of milia develop suddenly
      on the face and upper trunk. Rare isolated cases have been reported; however
      there has not been a review of these cases or an attempt to classify them. The
      authors report an additional case, review the literature, and suggest a
      classification of multiple eruptive milia.

PMID- 9270548
TI  - Ossifying fasciitis of the nose.
AB  - A case of ossifying fasciitis in a 22-year-old woman is described. The lesion,
      which appeared suddenly, was located on the tip of the nose. Histologically the
      lesion contained spindle-shaped myofibroblastic cells, trabeculae of woven bone
      rimmed by plump osteoblasts within a myxoid stroma.

PMID- 9270549
TI  - Metastatic involvement of four eyelids.

PMID- 9270550
TI  - The genetics of psoriasis.
AB  - The analysis of population-specific human leukocyte antigen (HLA) haplotypes has
      provided evidence that susceptibility to psoriasis is linked to the class I and
      II major histo-compatibility complex on human chromosome 6. In addition, these
      studies show that psoriasis consists of two distinct disease subtypes (type I and
      type II), which differ in age of onset and in the frequency of HLA. In type I
      (early-onset) psoriasis, Cw6, B57, and DR7 are strongly increased, whereas in
      type II (late-onset) psoriasis, HLA-Cw2 is overrepresented. It has also been
      proposed that HLA haplotypes extended by class III play a role in the genetics of
      this disease. Moreover, studies of affected families indicate that other disease
      susceptibility loci may also be involved. Likely candidates for additional
      susceptibility genes are located at chromosomes 1, 6, and 17, and microsatellite
      markers over the whole genome have been used to identify susceptibility genes.
      Two years ago linkage to the distal part of chromosome 17 was published. However,
      this linkage could not be confirmed by other groups with comparable or enlarged
      numbers of psoriatic family members investigated. Recently, an investigation
      presenting an area of chromosome 4 as a susceptibility locus for psoriasis was
      published. According to our knowledge today, psoriasis is a polygenetically
      inherited disease. Furthermore from twin studies it is known that environmental
      factors play a significant role in the onset or recurrence of the disease.

PMID- 9270551
TI  - Tazarotene: the first receptor-selective topical retinoid for the treatment of
      psoriasis.
AB  - Tazarotene belongs to a novel, nonisomerizable class of retinoic acid receptor
      (RAR)-specific retinoids, the acetylenic retinoids, and is the first topical
      retinoid developed for the treatment of psoriasis. Tazarotene targets the
      keratinocyte and modulates the major causes of psoriasis. Tazarotene is rapidly
      metabolized by esterase to the active free acid tazarotenic acid, which is
      rapidly eliminated in animal species. Tazarotene selectively transactivates RAR
      beta and RAR gamma subtypes and is inactive at retinoid X receptors (RXRs). This
      receptor selectivity could contribute to an optimized therapeutic index.
      Tazarotene has low systemic absorption after topical administration. In
      preclinical toxicity studies, high topical doses produced reversible topical
      irritation, and lower doses were well tolerated. Topical doses were neither
      teratogenic nor carcinogenic and were not sensitizing, phototoxic, or
      photosensitizing. The topical delivery of tazarotene and limited systemic
      exposure apparently result in a very low potential for systemic effects.

PMID- 9270552
TI  - Molecular mechanisms of tazarotene action in psoriasis.
AB  - Psoriasis is a chronic immune-mediated disease that is characterized by the
      hyperproliferation and abnormal differentiation of keratinocytes and by
      inflammation. The epidermal changes associated with psoriasis may be due to the
      infiltration of inflammatory T lymphocytes and the release of cytokines in
      response to antigenic stimulation. Tazarotene is a retinoic acid receptor
      specific retinoid with demonstrated efficacy in the topical treatment of
      psoriasis. Tazarotene down-regulates markers of keratinocyte differentiation,
      keratinocyte proliferation, and inflammation. The drug also up-regulates three
      novel genes TIG-1 (tazarotene-induced gene-1), TIG-2, and TIG-3, which may
      mediate an antiproliferative effect. The effect of tazarotene on these markers is
      probably a direct effect on gene expression rather than an indirect effect
      associated with disease improvement.

PMID- 9270553
TI  - Clinical safety of tazarotene in the treatment of plaque psoriasis.
AB  - Oral retinoids are effective in the treatment of psoriasis, but their use is
      limited by concerns for teratogenic potential and systemic side effects.
      Tazarotene is a novel acetylenic retinoid undergoing clinical trials for the
      topical treatment of mild-to-moderate plaque psoriasis. The safety and
      tolerability of tazarotene 0.1% and 0.05% gels were examined in a series of
      preclinical and clinical trials. In preclinical studies topically applied
      tazarotene gel was nonmutagenic, noncarcinogenic, and nonteratogenic. Tazarotene
      gel was not sensitizing, phototoxic, or photosensitizing in a series of studies
      in human volunteers. Treatment-related systemic adverse effects were not observed
      in clinical trials involving approximately 2000 patients treated with tazarotene
      0.1% or 0.05% gel for periods of up to 1 year. Adverse effects appear limited to
      manageable, mainly mild-to-moderate local skin irritation.

PMID- 9270555
TI  - Medicare's resource-based relative value scale, a de facto national fee schedule:
      its implications and uses for neurologists.
AB  - The institution of the RBRVS as a basis of Medicare reimbursement corrects some
      long-standing inequities. First, it corrects the magnitude of reimbursement of
      procedures compared with cognitive services. Second, it corrects unexplained
      geographical variations in reimbursement. The RBRVS continues to go through
      refinement. The 5-year review and HCFA's practice expense project are likely to
      further improve reimbursement for cognitive services. Furthermore, because of the
      strengths of the scale, the RBRVS is now employed by most payors and is a useful
      practice management tool. Relative to other specialties, particularly the
      surgical specialties, neurology has in general benefited from these changes. Yet
      the RBRVS only addresses the rate of reimbursement; the proliferation of plans
      and insurance products with different coverage and payment policies and different
      procedures vastly complicates medical practice management. Understanding the
      development and evolution of the RBRVS is one necessary element of competent
      practice management.

PMID- 9270554
TI  - Tazarotene gel: efficacy and safety in plaque psoriasis.
AB  - Tazarotene is the first of a new generation of acetylenic retinoids developed for
      the topical treatment of mild-to-moderate plaque psoriasis. Controlled clinical
      trials have demonstrated that once-daily tazarotene 0.05% and 0.1% gels are
      effective in improving and reducing clinical signs and symptoms of psoriasis on
      trunk and limb lesions and difficult-to-treat elbow and knee plaques. Tazarotene
      has a rapid onset of action indicated by significant improvements as early as the
      first week of treatment. Sustained beneficial effects have been observed in some
      patients for up to 12 weeks after the cessation of therapy. Compared with twice
      daily fluocinonide 0.05% cream, once-daily tazarotene 0.05%, and 0.1% gels were
      similarly effective in reducing plaque elevation. Once-daily tazarotene 0.05% and
      0.1% gels demonstrated a more prolonged therapeutic effect after discontinuation
      than twice-daily fluocinonide cream. Tazarotene is generally well tolerated, with
      adverse events limited to local irritation. Tazarotene appears to be an effective
      addition to the currently available treatments for plaque psoriasis.

PMID- 9270556
TI  - Managed care and neurologists: ethical considerations. The Ethics and Humanities
      Subcommittee of the Practice Committee of the American Academy of Neurology.

PMID- 9270557
TI  - On the role of veterans in the development of neurology in the United States: a
      personal reflection.

PMID- 9270558
TI  - Difficulties in extrapolating from clinical trial data to clinical practice: the
      case of antiepileptic drugs.
AB  - Effective new antiepileptic drugs (AEDs) are needed for the treatment of those
      with refractory epilepsy. However, with the growing number of these drugs being
      licensed and marketed, a rational approach to the treatment of epilepsy is
      becoming essential. New AED trials can determine appropriate use of AEDs but
      ultimately fail to determine the best use of AEDs and their exact role in
      treating patients. New AED trials rarely use clinically applicable measures of
      efficacy, and it is difficult to extrapolate the data from populations used in
      AED trials to the wider population of patients with epilepsy. Furthermore, AED
      trials ignore the factors that are most likely to determine prognosis: the
      etiology, seizure types, and epilepsy syndrome. To resolve these issues, we need
      large multicenter studies in well-defined populations with well-characterized
      seizures, epilepsy syndromes, and etiologies. Being seizure free should be the
      primary measure of efficacy rather than meta-analyses and guidelines based upon
      incomplete data.

PMID- 9270559
TI  - Change in the Department of Veterans Affairs: what should be done?
AB  - Health care in the Department of Veterans Affairs is undergoing the most dramatic
      change since the era following World War II. The Congress has supported the
      Undersecretary for Health in his guidance of this change. Traditional hospital
      based, specialty-focused care has given way to outpatient and primary care
      focused health care. Administrative authority has been shifted to 22 Veterans
      Integrated Service Networks (VISNs). Research goals are being reoriented, and
      neurology resident allocation is being reduced. VA neurologists and neurology
      chairs must organize strong service lines in their own VA facilities and in their
      networks to provide care for veterans with neurologic diseases. VA neurologists
      must also emphasize their role in principal care and increase their involvement
      in outcomes research.

PMID- 9270560
TI  - Ictal motor signs and interictal regional cerebral hypometabolism.
AB  - Early motor manifestations are the main components of focal seizures involving
      the frontal lobe. We examined the relationship between the initial ictal motor
      manifestations and interictal abnormalities of cerebral glucose consumption
      (rCMRGlc) as assessed by PET in 48 consecutive patients with focal seizures of
      neocortical origin. Group data analysis revealed that patients with predominantly
      unilateral clonic seizures had a significant contralateral perirolandic
      hypometabolism and to a lesser degree a contralateral frontomesial
      hypometabolism. Patients with predominantly focal tonic manifestations showed a
      hypometabolism within the frontomesial and perirolandic regions that was
      unilateral in all patients with lateralized tonic seizures. Patients with versive
      seizures had mainly contralateral metabolic depressions without a consistent
      regional pattern. Patients with hypermotor seizures had metabolic depressions
      involving frontomesial, anterior cingulate, perirolandic, and anterior
      insular/frontal operculum areas. In all patient groups, bilateral and symmetric
      hypometabolism of the thalamus and cerebellum was observed. We propose that this
      pattern of distinctly abnormal metabolic brain regions demonstrates not only
      possible epileptogenic zones but also symptomatogenic brain regions as shown by
      the associations between clinical manifestations and sets of abnormal brain
      regions, particularly if epileptogenic zones are in a clinically silent
      neocortical brain region. The detection and possible differentiation of
      symptomatogenic and epileptogenic zones might improve the effectiveness of
      presurgical noninvasive studies.

PMID- 9270561
TI  - Treatment of multiple sclerosis with the monoclonal anti-CD4 antibody cM-T412:
      results of a randomized, double-blind, placebo-controlled, MR-monitored phase II
      trial.
AB  - We report the results of a randomized, double-blind, placebo-controlled
      exploratory trial of the chimeric monoclonal anti-CD4 antibody cM-T412 in 71
      patients suffering from active relapsing-remitting and secondary progressive
      multiple sclerosis. Infusion of the antibody produced frequent but usually minor
      side effects and resulted in a long-lasting reduction of circulating CD4-positive
      T cells. There was no significant effect on the primary measure of efficacy, the
      number of active lesions on monthly gadolinium-enhanced MRI over 9 months.
      Further statistical evaluation provided evidence that the degree of depletion of
      CD4-positive cells was important with regard to treatment efficacy; using CD4
      counts as a covariate there was a statistically significant effect on the number
      of active lesions over 18 months (p = 0.04). There was a statistically
      significant reduction of 41% in the number of clinical relapses (a secondary
      efficacy parameter) after 9 months (p = 0.02), which was still present after 18
      months, but this finding may be partly due to physician unblinding. Other
      secondary efficacy parameters (Expanded Disability Status Scale progression,
      number of courses of methylprednisolone) were not influenced by anti-CD4
      treatment. We conclude that intravenous treatment with the monoclonal antibody cM
      T412 in the dosage we used results in a substantial and sustained reduction of
      the number of circulating CD4-positive cells, but is not able to reduce MS
      activity as measured by monthly gadolinium-enhanced MRI, and is therefore
      unlikely to have a beneficial effect on the clinical disease course. We found
      preliminary evidence suggesting that more aggressive depletion of CD4-positive
      cells might lead to a more substantial reduction in MRI activity.

PMID- 9270563
TI  - Multiple sclerosis lesion detection in the brain: a comparison of fast fluid
      attenuated inversion recovery and conventional T2-weighted dual spin echo.
AB  - We performed fast fluid-attenuated inversion recovery (fFLAIR) and conventional
      spin echo (CSE) brain MRI in 32 multiple sclerosis (MS) patients (eight each
      benign, relapsing-remitting, primary progressive, and secondary progressive). We
      compared number and site of lesions detected on each sequence. With initial
      separate assessment, we identified a total of 3,668 lesions-2,892 by CSE and
      2,943 by fFLAIR. Following simultaneous review of the sequences, we identified an
      additional 217 lesions on fFLAIR and 229 on CSE. fFLAIR detected fewer lesions in
      the posterior fossa (66 versus 138, p = 0.001), fewer small (< 5 mm) discrete
      cerebral white matter lesions (671 versus 829, p = 0.0002), more subcortical
      lesions (542 versus 306, p < 0.0001), and more large discrete lesions (419 versus
      385, p = 0.0006). Its relatively poor detection of posterior fossa lesions makes
      it premature for fFLAIR to replace CSE as the primary sequence for detecting MS
      lesions in clinical trials.

PMID- 9270562
TI  - Impact of interferon beta-1a on neurologic disability in relapsing multiple
      sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG).
AB  - BACKGROUND AND OBJECTIVE: A phase III double-blind, placebo-controlled clinical
      trial demonstrated that interferon beta-1a (IFN beta-1a) (Avonex, Biogen)
      significantly delayed progression of disability in relapsing MS patients. The
      primary clinical outcome was time from study entry until disability progression,
      defined as > or = 1.0 point worsening from baseline Kurtzke Expanded Disability
      Status Scale (EDSS) score persisting for at least two consecutive scheduled
      visits separated by 6 months. The objective of this study was to examine the
      magnitude of benefit on EDSS and its clinical significance. METHODS: Post hoc
      analyses related to disability outcomes using data collected during the double
      blind, placebo-controlled phase III clinical trial. RESULTS: (1) Clinical
      efficacy related to disability did not depend on the definition of disability
      progression. A significant benefit in favor of IFN beta-1a was observed when > or
      = 2.0 point worsening from baseline EDSS was required or when worsening was
      required to persist for > or = 1.0 year. (2) Placebo recipients who reached the
      primary clinical outcome worsened by a larger amount from baseline EDSS than did
      IFN beta-1a recipients who reached the primary study outcome. (3) Significantly
      fewer IFN beta-1a recipients progressed to EDSS milestones of 4.0 (relatively
      severe impairment) or 6.0 (unilateral assistance needed to walk). (4) Cox
      proportional hazards models demonstrated that the only baseline characteristic
      strongly correlated with longer time to disability progression was IFN beta-1a
      treatment. CONCLUSIONS: The primary clinical outcome for the IFN beta-1a clinical
      trial underestimated clinical benefits of treatment. Results in this report
      demonstrate that IFN beta-1a treatment is associated with robust, clinically
      important beneficial effects on disability progression in relapsing MS patients.

PMID- 9270564
TI  - Interscanner variation in brain MRI lesion load measurements in MS: implications
      for clinical trials.
AB  - We evaluated the effect of interscanner variation on brain MRI-measured lesion
      volumes and measurement reproducibility in MS. Twenty clinically definite MS
      patients were each scanned on two or three scanners (a total of 14 scanners were
      used). In addition, a formalin-fixed MS brain was studied on eight scanners from
      different manufacturers and with different field strengths. For the formalin
      fixed MS brain, on each machine we obtained two scans with slice thicknesses of 5
      and 3 mm. Only 5-mm-thick slices were obtained from patients. The lesion volume
      present on each scan was evaluated three times by a single observer in random
      order, using a local thresholding technique. In two groups of eight patients
      scanned on machines with different field strengths, the mean lesion volumes
      present on scans obtained at 1.5 T were significantly higher than those measured
      on scans obtained with machines operating at 0.5 and 1.0 T (p < 0.01). When a
      single observer repeatedly evaluated the same scan, a median introbserver
      agreement of 98.7% (95% CI, 97.9 to 99.1) was achieved. However, when the
      observer evaluated the scans from different MRI scanners, the agreement (an
      interscanner agreement) fell to 91.1% (CI, 90.2 to 94.1). When only scanners
      operating at 1.5 T were considered, the median interscanner agreement was 96.7%
      (CI, 95 to 97.5). Also, for the formalin-fixed MS brain, the intraobserver
      agreements obtained with both slice thicknesses were significantly higher than
      the corresponding interscanner agreements. The interscanner agreement, but not
      the intraobserver agreement, obtained with a slice thickness of 3 mm was higher
      than that obtained with a slice thickness of 5 mm. Our results indicate that
      lesion volume measurements in MS are influenced significantly by the use of
      different MR scanners and that a patient included in a serial study should be
      always scanned with the same MR machine using 3-mm thick slices.

PMID- 9270565
TI  - Genetic variation in the tumor necrosis factor alpha gene and the outcome of
      multiple sclerosis.
AB  - The objective of this study was to determine whether sequence variation in the
      tumor necrosis factor alpha (TNF alpha) gene is associated with MS course and
      severity in Olmsted County, MN. The severity and temporal course of MS are
      heterogeneous. Genetic factors may play a role in determining the course of MS.
      TNF alpha expression is temporally associated with exacerbations of MS and is
      increased in individuals with progressive disease. The entire TNF alpha gene was
      amplified by polymerase chain reaction in 78 MS patients and in 39 patients with
      schizophrenia. Denaturation finger-printing, a modification of direct sequencing
      that detects virtually all genetic polymorphisms, was performed for four regions
      spanning the functionally significant portions of the gene, including the
      promoter region. Polymorphisms were confirmed by complete sequencing. The
      severity and temporal course of MS were compared in those with wild-type versus
      variant alleles. Four sequence changes were detected, three of which occurred in
      MS patients. None occurred in a protein-encoding sequence. Neither of the two
      most common sequence variants were associated with disease severity or temporal
      course. Genetic variation of the TNF alpha gene is not associated with variation
      in the course or long-term outcome of MS in this population-based sample.

PMID- 9270566
TI  - Interferon-beta interferes with the proliferation but not with the cytokine
      secretion of myelin basic protein-specific, T-helper type 1 lymphocytes.
AB  - Interferon-beta (IFN-beta) has beneficial effects on the frequency and severity
      of relapses, as well as on disease progression in patients suffering from
      relapsing-remitting MS. Its mode of action, however, is not completely
      understood. Previous studies on T-lymphocyte bulk cultures and T-lymphocyte lines
      with specificity for different antigens suggested that the drug might partially
      act via suppression of T-cell proliferation and secretion of proinflammatory
      cytokines like interferon-gamma (IFN-gamma) and/or tumor necrosis factor-alpha
      (TNF-alpha). In this study we investigated the effects of human recombinant IFN
      beta 1b on proliferation, interleukin 2 (IL-2) receptor (IL-2R) alpha-chain
      upregulation, and cytokine and chemokine secretion of myelin basic protein
      reactive, MS patient-derived T-cell clones secreting T-helper type 1 (Th1)
      cytokines. IFN-beta partially suppressed both antigen- and IL-2-driven
      proliferation of these cells without affecting the expression of either IL-2 or
      IL-2R alpha-chain. There was no inhibitory effect on the secretion of IFN-gamma,
      TNF-alpha, and macrophage inflammatory protein (MIP)-1 alpha, but release was
      rather slightly enhanced. In conclusion, while IFN-beta does reduce proliferation
      of Th1-like, MBP-specific T cells in vitro, the drug does not result in overall
      dysfunction of these cells. Therefore, the effect of IFN-beta on MS may not
      depend on a primary inhibition of potentially encephalitogenic T lymphocytes.

PMID- 9270567
TI  - Ropinirole for the treatment of early Parkinson's disease. The Ropinirole Study
      Group.
AB  - A prospective, randomized, placebo-controlled, double-blind, parallel-group, 6
      month study assessed the efficacy and safety of ropinirole, a nonergoline D2
      dopamine agonist, in patients with early Parkinson's disease (n = 241; Hoehn &
      Yahr stages I to III) with limited or no prior dopaminergic therapy. Patients
      (mean age, 62.8 years), stratified by concomitant use of selegiline, were
      randomized to ropinirole (n = 116) or placebo (n = 125). The starting dose of
      ropinirole was 0.25 mg tid with titration to at least 1.5 mg tid (maximum dose, 8
      mg tid). Primary efficacy endpoint was the percentage improvement in Unified
      Parkinson's Disease Rating Scale (UPDRS) motor score. Ropinirole-treated patients
      had a significantly greater percentage improvement in UPDRS motor score than
      patients who received placebo (+24% vs -3%; p < 0.001). Ropinirole was well
      tolerated and patient withdrawals were infrequent. Most adverse experiences were
      related to peripheral dopaminergic activity. Ropinirole monotherapy is an
      effective and well-tolerated therapeutic option for treatment of early
      Parkinson's disease.

PMID- 9270568
TI  - Familial nature and continuing morbidity of the amyotrophic lateral sclerosis
      parkinsonism dementia complex of Guam.
AB  - Chamorros suffer from two neurologic syndromes known as ALS and the parkinsonism
      dementia complex (PDC) of Guam. We report mortality figures for these syndromes
      during 1991 to 1995 and compare them with those at 5-year intervals dating back
      to 1951. In contrast to predictions of disease disappearance, both syndromes
      remain prevalent. However, age of onset and age at death have increased for both
      syndromes, suggesting that shifting environmental factors are causing disease
      postponement. We also report the clinical, familial, neuropathologic, and
      immunohistochemical findings on a consecutive autopsy series of Guamanian
      Chamorro cases. Twelve cases were diagnosed as PDC, known locally as "bodig," and
      three as ALS, known locally as "lytico." All but three of these fifteen patients
      had a pronounced family history of similar illness. Eight of twelve boding
      patients had siblings who were also affected with bodig; two of three lytico
      cases had siblings afflicted with lytico. The family histories are compatible
      with genetic transmission of each syndrome. The neuropathology of bodig is
      characterized by severe and widespread neurofibrillary tangle (NFT) development.
      NFTs are surrounded by reactive microglia and reactive astrocytes, and complement
      proteins and other molecules connected with inflammation are associated with
      them. Similar inflammatory responses also occur in Alzheimer's disease (AD) but
      have been largely attributed to the presence of senile plaques. These data
      indicate that tangles, as well as plaques, generate inflammatory reactions that
      such reactions may exacerbate the fundamental pathology in bodig as well as in
      AD.

PMID- 9270569
TI  - A volumetric MRI study of Gilles de la Tourette's syndrome.
AB  - The neuroanatomic or neuropathologic basis of Gilles de la Tourette's syndrome
      (GTS) remains unknown. Recent studies have suggested abnormalities of cerebral
      asymmetry and basal ganglia volumes. We studied 17 patients with GTS and eight
      normal controls using volumetric MRI techniques for measuring the caudate
      nucleus, amygdala, and corpus callosum. One subject with GTS was subsequently
      excluded because he was left handed. No absolute differences in caudate nucleus
      volumes between patient and control groups were evident. There was an increase in
      corpus callosum (CC) cross-sectional area and a loss of the normal asymmetry of
      the caudate nucleus in the patient group. A loss of the normal correlation
      between cross-sectional area of the CC and whole brain index (WBI) in the patient
      group also was found. The amygdala measurements had a poor interrater
      reliability.

PMID- 9270570
TI  - Functional MRI mapping of occipital and frontal cortical activity during
      voluntary and imagined saccades.
AB  - We investigated the activation of frontal and occipital cortical areas in 14
      normal volunteers during voluntary saccades in light or dark and during imagined
      saccades using functional magnetic resonance imaging (FMRI) with electro
      oculogram monitoring. Voluntary saccades in light or dark and imagined saccades
      led to a significant activation (p < 0.005) of the precentral and posterior
      medial frontal gyrus (frontal eye field). The medial part of the superior frontal
      gyrus (supplementary eye field) also showed significant activity during voluntary
      saccades in all subjects, but only in four subjects during imagined saccades. In
      addition to frontal activity we found an activated primary visual cortex during
      voluntary saccades, both in light and in dark. In contrast to executed saccades,
      imagined eye movements revealed to occipital response under either condition. Our
      FMRI study supports the concept of frontal eye fields during voluntary saccades
      and demonstrates that occipital areas are associated with the generation of
      voluntary eye movements. However, the primary visual cortex is not active when
      eye movement is only imagined.

PMID- 9270571
TI  - Potential therapeutic use of the selective dopamine D1 receptor agonist, A-86929:
      an acute study in parkinsonian levodopa-primed monkeys.
AB  - The clinical utility of dopamine (DA) D1 receptor agonists in the treatment of
      Parkinson's disease (PD) is still unclear. The therapeutic use of selective DA D1
      receptor agonists such as SKF-82958 (6-chloro-7,8-dihydroxy-3-allyl-1-phenyl
      2,3,4,5-tetrahydro-1H-3-benzaze pine hydrobromide) and A-77636 ([1R, 3S] 3-[1'
      admantyl]-1-aminomethyl-3,4-dihydro-5,6-dihydroxy-1H-2-benzo pyran hydrochloride)
      seems limited because of their duration of action, which is too short for SKF
      82958 (< 1 hr) and too long for A-77636 (> 20 hr, leading to behavioral
      tolerance). We therefore conducted the present acute dose-response study in four
      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-exposed cynomolgus monkeys
      primed to exhibit levodopa-induced dyskinesias to evaluate the locomotor and
      dyskinetic effects on challenge with four doses (from 0.03 to 1.0 mg/kg) of A
      86929 ([-]-[5aR,11bS]-4,5,5a,6,7,11b-hexahydro-2-propyl-3-thia-5-+ ++azacyclopent
      1- ena[c]phenathrene-9-10-diol), a selective and full DA D1-like receptor agonist
      with an intermediate duration of action. Levodopa and the DA D2-like receptor
      agonist, LY-171555 ([4aR-trans]-4,4a,5,6,7,8,8a,9-o-dihydro-5n-propyl-2H-pyrazo
      lo-3-4-quinoline hydrochloride) were also used for comparison. Acute
      administration of A-86929 was as efficacious in alleviating MPTP-induced
      parkinsonism as levodopa and LY-171555, but was less likely to reproduce the
      levodopa-induced dyskinesias in these animals than with either LY-171555 or
      subsequent challenge of levodopa. Selective stimulation of the DA D1 receptor may
      provide better integration of neural inputs transmitted to the internal segment
      of the globus pallidus (referred to as the basal ganglia output) compared with
      levodopa and selective DA D2 receptor agonist. Potent DA D1 receptor agents with
      an intermediate duration of efficacy such as A-86929 (approximately 4 hr at
      higher doses tested) are potential therapeutic tools in PD and merit further
      attention.

PMID- 9270572
TI  - High prevalence of Parkinson's disease in the Faroe Islands.
AB  - We used several case-findings methods and strict criteria for case ascertainment
      to diagnose parkinsonism and idiopathic Parkinson's disease (PD) in the Faroe
      Islands. In the last few years before the prevalence date of July 1, 1995, we
      searched various registries from pharmacies, hospitals, and general practices,
      and found 195 patients with suspected parkinsonism out of 43,709 inhabitants.
      After excluding those who died before the prevalence date or were treated with
      levodopa (LD) for other diseases, a total of 124 patients remained for study, of
      whom 122 participated. We found 102 patients with parkinsonism and 82 with PD
      versus the expected 53 (p < 0.001, age-specific prevalences in the county of
      Rogaland, Norway). The overall prevalence of PD was estimated to be 187.6 and the
      age-adjusted prevalence to be 183.3 versus 110.9 per 100,000 inhabitants in the
      county of Rogaland. Compared to the study from Rogaland, the mean age at onset of
      PD symptoms, the mean age at the prevalence date, and the duration of PD
      indicated that the higher prevalence was not due to either an early onset nor to
      a longer duration of PD. A lower proportion of definite PD, a lower mean score on
      the Hoehn-Yahr scale, and a lower average dose of LD suggest that the high
      prevalence may be due to early diagnosis and a higher ascertainment of cases with
      mild disease. However, a high incidence cannot be excluded.

PMID- 9270573
TI  - Spinal pseudoathetosis: a rare, forgotten syndrome, with a review of old and
      recent descriptions.
AB  - We report a patient with a cervical spinal astrocytoma who presented with
      athetotic hand movements. We postulate that acute pain, related to a syrinx
      around the operative site, contributed to the athetosis. These movements occur
      only after protracted, severe loss of proprioception, often in conjunction with
      an acute, generally painful crisis. Athetotic movements can disappear without
      change in proprioceptive or motor deficits when pain lessens.

PMID- 9270574
TI  - Changes in putamen N-acetylaspartate and choline ratios in untreated and levodopa
      treated Parkinson's disease: a proton magnetic resonance spectroscopy study.
AB  - We have carried out single-voxel proton magnetic resonance spectroscopy centered
      on the putamen both ipsilateral and contralateral to the worst affected side in
      nine subjects with drug naive idiopathic Parkinson's disease (IPD); seven
      chronically levodopa-treated dyskinetic IPD subjects; and 11 age-matched healthy
      controls. Measurements of N-acetylaspartate (NAA)/choline (Cho), NAA/(Creatine +
      Phosphocreatine) (Cr + PCr), and Cho/(Cr + PCr) were made. We found a significant
      reduction in NAA/Cho ratios from the putamen contralateral to the most affected
      side in the drugnaive group (p = 0.009), but not the levodopa-treated IPD groups
      compared with controls. There were no significant differences in NAA/(Cr + PCr)
      or Cho/(Cr + PCr) ratios. In untreated IPD, reduced putaminal NAA/Cho ratios may
      reflect loss of nigrostriatal dopamine terminals or alternatively indicate a
      functional abnormality of striatal putaminal neurons, such as membrane
      dysfunction due to striatal deafferentation. This study suggests that NAA/Cho
      ratios may be affected by L-dopa therapy and this may provide a reversible marker
      of neuronal dysfunction in the striatum.

PMID- 9270575
TI  - Randomized, double-blind, placebo-controlled crossover trial of modafinil in the
      treatment of excessive daytime sleepiness in narcolepsy.
AB  - Seventy-five patients meeting international diagnostic criteria for narcolepsy
      enrolled in a 6-week, three-period, randomized, crossover, placebo-controlled
      trial. Patients received placebo, modafinil 200 mg, or modafinil 400 mg in
      divided doses (morning and noon). Evaluations occurred at baseline and at the end
      of each 2-week period. Compared with placebo, modafinil 200 and 400 mg
      significantly increased the mean sleep latency on the Maintenance of Wakefulness
      Test by 40% and 54%, with no significant difference between the two doses.
      Modafinil, 200 and 400 mg, also reduced the combined number of daytime sleep
      episodes and periods of severe sleepiness noted in sleep logs. The likelihood of
      falling asleep as measured by the Epworth Sleepiness Scale was equally reduced by
      both modafinil dose levels. There were no effects on nocturnal sleep initiation,
      maintenance, or architecture, nor were there any effects on sleep apnea or
      periodic leg movements. Neither dose interfered with the patients' ability to nap
      voluntarily during the day nor with their quantity or quality of nocturnal sleep.
      Modafinil produced no changes in blood pressure or heart rate in either
      normotensive or hypertensive patients. The only significant adverse effects were
      seen at the 400-mg dose, which was associated with more nausea and more
      nervousness than either placebo or the 200-mg dose. As little as a 200-mg daily
      dose of modafinil is therefore an effective and well-tolerated treatment of
      excessive daytime somnolence in narcoleptic persons.

PMID- 9270576
TI  - Spinal epidural metastasis as the initial manifestation of malignancy: clinical
      features and diagnostic approach.
AB  - The objective of our study was to delineate clinical features and specific
      diagnostic and therapeutic implications of spinal epidural metastasis (SEM)
      occurring as the initial manifestation of malignancy (IMM)-a less common event
      than SEM in the setting of previously established malignancy (PEM). We performed
      a retrospective review of the clinical histories of 337 patients seen at Mayo
      Clinic with a radiographically verified diagnosis of SEM between January 1, 1985,
      and December 31, 1993. Twenty percent of all cases of SEM occurred as SEM-IMM.
      Carcinoma of the lung, cancer of unknown primary site, multiple myeloma, and non
      Hodgkin's lymphoma were disproportionately represented in SEM-IMM, together
      accounting for 78% of SEM-IMM patients and only 26% of SEM-PEM patients.
      Inversely, breast and prostate carcinoma contributed only 12% of SEM-IMM patients
      but 51% of SEM-PEM patients. Only 27% of patients with SEM-IMM had nonspecific
      symptoms suggesting malignancy, and in only 24% did the history or physical
      examination suggest the primary site of malignancy. Percutaneous needle biopsy of
      the vertebral lesion was diagnostic of malignancy in 18 of 19 patients (95%), and
      no complications ensued. Fifteen patients underwent diagnostic laminectomy with
      biopsy, and one had a fatal complication. Survival after the diagnosis of SEM did
      not differ between patients with SEM-IMM and those with SEM-PEM; the median
      survival was 6.6 months. SEM not uncommonly occurs as the presentation of
      malignancy, and often it produces the only symptoms or signs of malignancy. The
      great majority of neoplasms presenting with SEM are carcinomas of the lung,
      unknown primary lesions, and hematologic malignancies. Computed tomography-guided
      needle biopsy is a safe, efficacious means of diagnosing malignancy, allowing for
      rational diagnostic workup and staging. In most patients it obviates a diagnostic
      spinal surgical procedure.

PMID- 9270577
TI  - Conceptual apraxia from lateralized lesions.
AB  - Models of praxis have posited two major components, production and conceptual.
      Conceptual praxis disorders may occur in two domains: associative knowledge (tool
      action associations such as hammer pound; tool-object associations such as hammer
      nail) and mechanical knowledge such as knowing the advantage that tools afford.
      Patients with Alzheimer's disease not only have conceptual apraxia (CA) but can
      dissociate CA from language deficits and from praxis production deficits
      (ideomotor apraxia). These findings suggests that knowledge about tools (action
      semantics) is independent of verbal semantics as well as movement
      representations. To learn if conceptual praxis knowledge is stored in one
      hemisphere (right or left) and if associative and mechanical conceptual praxis
      knowledge can be dissociated, we studied 29 right-handed subjects with unilateral
      strokes. Ten had left-hemisphere damage with no ideomotor apraxia. Eleven had
      left-hemisphere damage with ideomotor apraxia. There were eight right-hemisphere
      damaged controls and 10 normal controls. These subjects were given tests for
      conceptual apraxia. There was a significant difference between groups, the left
      hemisphere group with ideomotor apraxia being most impaired on both the
      associative and mechanical CA tests. There was a trend for associative and
      mechanical knowledge to be dissociated. Although conceptual praxis
      representations are stored in the left hemisphere, analysis of lesion sites did
      not reveal where in the left hemisphere they may be stored.

PMID- 9270578
TI  - Pure topographic disorientation due to right retrosplenial lesion.
AB  - We report three patients with selective topographic disorientation due to small,
      focal hemorrhages extending from the right retrosplenial region to the medial
      parietal lobe. All three could discriminate and identify familiar buildings and
      landscapes, but had great difficulty remembering spatial positional relationships
      between two distant locations (i.e., the direction from one location to another)
      in familiar areas. These symptoms were different than the perception and memory
      deficits for buildings and landscapes caused by the medial temporo-occipital
      lesion. These findings suggest that the directional orientation between two
      locations within a familiar area ("sense of direction") is closely associated
      with the right retrosplenial region and the medial parietal lobe in humans.

PMID- 9270579
TI  - Audiogenic startle reflex in acute hemiplegia.
AB  - The generators of the audiogenic startle reflex (ASR) are located in the
      bulbopontine reticular formation. We studied the influence of acute vascular
      supratentorial lesions on ASR. Ten patients with hemiplegia due to hemispheric
      cerebral infarct were studied within 5 days of stroke onset. ASR and magnetic
      cortical stimulation were performed the same day. A muscle response to magnetic
      stimulation was not elicited over the plegic side in any patient. In four of
      seven patients, ASR was enhanced over the plegic side. We suggest that enhanced
      ASR is due to the loss of a predominantly inhibitory hemispheric drive on ASR
      generators.

PMID- 9270580
TI  - Selective deficit of praxis imagery in ideomotor apraxia.
AB  - We studied imagery for learned, skilled movements (praxis imagery) in a patient
      with severe ideomotor apraxia and intact language abilities. This patient, who
      made predominantly spatial and movement errors when performing transitive
      movements demonstrating the use of tools (transitive gestures), was also impaired
      in her ability to answer imagery questions about joint movement or the spatial
      position of the hands during action. However, visual object imagery was spared.
      The finding of parallel praxis production and praxis imagery deficits in this
      patient suggests that the same representations used for gesture production are
      also activated during imagery of motor acts. Our findings also suggest that
      certain aspects of motor imagery may be dissociable from general object imagery.

PMID- 9270581
TI  - Individual prediction of change in delayed recall of prose passages after left
      sided anterior temporal lobectomy.
AB  - Prognostic variables for individual memory outcome after left anterior temporal
      lobectomy (ATL) were studied in 27 patients with refractory temporal lobe
      epilepsy. The difference between pre- and postoperative performance in the
      delayed recall of two prose passages (Story A and B) from the Wechsler Memory
      Scale served as measure of postoperative memory change. Fifteen independent
      clinical, neuropsychological, and electrophysiological variables were submitted
      to a multiple linear regression analysis. Preoperative immediate and delayed
      recall of story content and right hemisphere Wada memory performance for
      pictorial and verbal items explained very well postoperative memory changes in
      recall of Story B. Delayed recall of Story B, but not of Story A, had high
      concurrent validity to other measures of memory. Patients who became seizure-free
      did not differ in memory change from patients who continued to have seizures
      after ATL. The variables age at epilepsy onset and probable age at temporal lobe
      damage provided complementary information for individual prediction but with less
      effectiveness than Wada test data. Our model confirmed that good preoperative
      memory functioning and impaired right hemispheric Wada memory performance for
      pictorial items predict a high risk of memory loss after left ATL. The analyses
      demonstrate that the combination of independent measures delivers more
      information than Wada test performance or any other variable alone. The suggested
      function can be used routinely to estimate the individual severity of verbal
      episodic memory impairment that might occur after left-sided ATL and offers a
      rational basis for the counseling of patients.

PMID- 9270582
TI  - Lateralized effects of self-induced sadness and happiness on corticospinal
      excitability.
AB  - We studied the changes in excitability of the corticospinal projection evoked by
      self-induced sad and happy thoughts. Corticospinal excitability was probed using
      focal, single-pulse transcranial magnetic stimulation (TMS) applied to the
      optimal scalp position for evoking motor potentials in the contralateral first
      dorsal interosseus muscle. Fourteen right-handed subjects were studied while
      counting mentally, thinking sad thoughts, or thinking happy thoughts. In each of
      these three conditions TMS was applied in each subject randomly, 20 times to the
      right and 20 times to the left hemisphere. Sad thoughts resulted in a significant
      facilitation of the motor potentials evoked by left-hemispheric stimulation,
      while happy thoughts facilitated motor potentials evoked by right-hemispheric
      TMS, but decreased the amplitude of those evoked by left-hemispheric TMS. In two
      subjects an additional experiment using H-reflex measurements suggests that these
      changes are caused by changes in cortical rather than spinal excitability. These
      results further illustrate the lateralized control of mood in normal volunteers.

PMID- 9270583
TI  - Partial ocular tilt reaction due to unilateral cerebellar lesion.
AB  - We report on two patients each with tonic, contraversive partial ocular tilt
      reactions due to unilateral cerebellar lesions: one patient had had a caudal
      cerebellar hemorrhage, the other a posterior inferior cerebellar artery territory
      infarct. Both patients had tonic contraversive conjugate ocular torsion; one had
      skew deviation; neither had a head tilt. One patient had no specific neurologic
      deficit apart from the conjugate ocular torsion, which was first suspected
      because of a deviation of the subjective visual horizontal. These observations
      imply that the ocular tilt reaction (OTR), a brainstem otolith-ocular reflex of
      probable utricular origin, is under the inhibitory control of the ipsilateral
      caudal cerebellum, possibly the nodulus, and that a patient with a cerebellar
      infarct can present with imbalance as the only neurologic symptom and with
      conjugate ocular torsion as the only specific neurologic sign.

PMID- 9270584
TI  - Anterior opercular syndrome, caused by herpes simplex encephalitis.
AB  - Bilateral frontal and parietal opercular lesions cause a syndrome characterized
      by paralysis of the masticatory, facial, pharyngeal, and tongue muscles (the
      anterior opercular syndrome). The anterior opercular syndrome can occur in
      patients with herpes simplex encephalitis (HSE), but in most of these patients
      the diagnosis of HSE was not confirmed. We describe the anterior opercular
      syndrome in four patients with HSE. In two of these patients, the anterior
      opercular syndrome dominated the clinical picture, but in the other two patients
      it was overshadowed by other manifestations of HSE. The diagnosis of HSE was
      confirmed by detection of herpes simplex virus (HSV) DNA in the CSF (two
      patients), culture of the HSV from a brain biopsy (one patient), and elevated HSV
      antibody titers in the CSF (one patient). Our patients made a partial recovery.
      Acute onset of weakness of masticatory, facial, pharyngeal, and glossal muscles,
      accompanied by fever, headache, and partial motor seizures of the face should
      suggest HSE.

PMID- 9270586
TI  - Increased intra-abdominal pressure and cardiac filling pressures in obesity
      associated pseudotumor cerebri.
AB  - OBJECTIVES: To determine whether intra-abdominal pressure (as estimated from
      urinary bladder pressure) is elevated in patients with central obesity (as
      measured by sagittal abdominal diameter) and pseudotumor cerebri and whether this
      increased intra-abdominal pressure is associated with increased pleural pressure
      and cardiac filling pressure, implying a resistance to venous return from the
      brain. DESIGN: Nonrandomized, prospective. SETTING: University hospital,
      operating room. MAIN OUTCOME MEASUREMENTS: Intracranial pressure, urinary bladder
      pressure, sagittal abdominal diameter, transesophageal pleural pressure, central
      venous pressure, pulmonary artery pressure, and pulmonary artery occlusion
      pressure. SUBJECTS: Six women with pseudotumor cerebri (one with CSF leak, one
      with lumboperitoneal shunt). RESULTS: Urinary bladder pressure (22 +/- 3 cm H2O)
      and sagittal abdominal diameter (29 +/- 3 cm) were significantly elevated in
      these patients with elevated intracranial pressure (293 +/- 80 mm H2O) compared
      with a previously reported group of nonobese control patients. The
      transesophageal pleural pressure (15 +/- 10 mm Hg), central venous pressure (20
      +/- 6 mm Hg), mean pulmonary artery pressure (31 +/- 6 mm Hg), and pulmonary
      artery occlusion pressure (21 +/- 7 mm Hg) were all markedly elevated compared
      with published normal values and with previous data from obese patients without
      pseudotumor cerebri. CONCLUSIONS: These data support the hypothesis that central
      obesity raises intra-abdominal pressure, which increases pleural pressure and
      cardiac filling pressure, which impede venous return from the brain, leading to
      increased intracranial venous pressure and increased intracranial pressure
      associated with pseudotumor cerebri.

PMID- 9270585
TI  - Frequent and frequently overlooked: treatment-induced endocrine dysfunction in
      adult long-term survivors of primary brain tumors.
AB  - New treatments for primary brain tumors have improved survival but quality of
      life may be impaired by neuroendocrine dysfunction. We performed a controlled,
      cross-sectional study to assess frequency and clinical impact of endocrine
      dysfunction in adult long-term survivors of primary brain tumors outside the
      hypothalamic-pituitary region. Thirty-one patients (19 males and 12 females; age,
      25 to 66 years) and 31 sex- and age-matched controls were studied 1.5 to 11 years
      after radiotherapy with a mean total dose of 62.3 +/- 2.8 Gy (mean local doses
      pituitary, 51.1 +/- 12.1 Gy; hypothalamus, 57.0 +/- 7.8 Gy). Structured clinical
      assessment included a standardized questionnaire. Thyroid, adrenal, and gonadal
      hormones were measured at baseline and, in the patients, also after stimulation.
      Sixteen patients (52%) reported two or more symptoms suggestive of
      hypothyroidism; eight patients (26%) showed evidence of hypothalamic
      hypothyroidism. Patients had significantly lower serum baseline concentrations of
      cortisol and dehydroepiandrosterone sulfate than controls, but no manifest
      hypoadrenalism was noticed except in one patient with panhypopituitarism. Forty
      seven percent of the male patients, but only six percent of the controls,
      suffered from erectile dysfunction; 42% of the male patients showed either
      evidence of hypothalamic hypogonadism (32%) or primary gonadal damage (10%). Nine
      patients (29%) presented with hyperprolactinemia and four women concurrently
      suffered from oligo-amenorrhea. In adult patients treated for primary brain
      tumors, endocrine dysfunction due to radiation-induced hypothalamic damage is
      common and has a significant impact on well being. Endocrinologic evaluation
      should be performed periodically in these patients.

PMID- 9270588
TI  - Expression of game-related and generic knowledge by dementia patients who retain
      skill at playing dominoes.
AB  - Patients with dementia who remain skilled at musical performance or playing
      bridge fail explicit memory tests for information related to their skills,
      suggesting that implicit memory mediates their preserved skills. To reexamine
      this issue, 23 dementia patients and 15 elderly controls of comparable domino
      playing skill were compared on tests of naming, verbal fluency, and domino
      knowledge. On an explicit test of domino knowledge, the patients scored well
      below the elderly controls, performing no better than students who were
      unfamiliar with the game. But when game-like situations were created with real
      dominoes, both the skilled controls and the patients with dementia chose optimal
      moves and verbally explained their choices equally well. On naming and fluency
      tests, the skilled patients showed no advantage over patients of comparable
      dementia severity who had no retained skill. In dementia, some complex knowledge
      seems intact but is accessible only in particular contexts.

PMID- 9270587
TI  - Evidence for association of HLA-A2 allele with onset age of Alzheimer's disease.
AB  - Our earlier studies had suggested a possible association between the HLA-A2
      allele and Alzheimer's disease (AD). In the present study we tested the
      hypothesis that A2 is associated with earlier AD onset. We performed two
      independent studies: a collaborative study with 111 patients and a confirmatory
      study with 96 patients. We found similar patterns of reduced age at onset as a
      function of A2 in both data sets. Overall, A2 was associated with a significant 3
      year shift to earlier onset. The effects of A2 and epsilon 4 on age at onset
      appeared additive. Our results suggest A2, or a closely linked gene, modulates
      onset age of AD. Association with A2 would suggest an immune/inflammatory
      response mechanism for AD.

PMID- 9270589
TI  - Probable diffuse Lewy body disease presenting as REM sleep behavior disorder.
AB  - Rapid eye movement sleep behavior disorder may herald several neurodegenerative
      disorders associated with parkinsonism, including Parkinson's disease. A 72-year
      old man with a 17-year history of rapid eye movement sleep behavior disorder
      confirmed by polysomnography developed a progressive dementia that met
      operational clinical criteria for diffuse Lewy body disease. The differential
      diagnosis of progressive neurodegenerative disorders heralding as rapid eye
      movement sleep behavior disorder should now include diffuse Lewy body disease.

PMID- 9270590
TI  - Relationship between mesial temporal seizure focus and elevated serum prolactin
      in temporal lobe epilepsy.
AB  - We evaluated the relationship between mesial temporal seizure focus and serum
      prolactin (PRL) in patients before and after they underwent anterior temporal
      lobectomy (ATL) for medically intractable temporal lobe epilepsy (TLE). These
      patients had a confirmed unilateral epileptogenic focus in mesial temporal
      structures, a postictal rise in serum PRL 15 to 20 minutes after onset of complex
      partial seizures, and were refractory for more than 2 years to antiepileptic
      drugs. Presurgical interictal serum PRL levels were significantly elevated (16.47
      +/- 0.85 ng/mL, n = 62) and declined after ATL to normal values (patients, 9.63
      +/- 0.55 ng/mL, n = 54; normal subjects, 8.99 +/- 0.57 ng/mL, n = 52). Serial
      evaluations indicated that normalization was seen 3 months after surgery (9.42 +/
      1.22 ng/mL, n = 9). The postsurgical reduction in serum PRL was similar in men
      and women, in patients with epileptogenic focus on either side of mesial temporal
      structures, and was unaffected by antiepileptic medication. We conclude that PRL
      is elevated following seizures and that a seizure focus in mesial temporal
      structures may exert a sustained excitatory influence on PRL release in patients
      with medically intractable TLE.

PMID- 9270591
TI  - Risk factors for status epilepticus in children with symptomatic epilepsy.
AB  - The purpose of this study was to determine risk factors for status epilepticus
      (SE) in children with symptomatic epilepsy through a retrospective case-control
      study. Patients (44 children with a prior diagnosis of symptomatic epilepsy
      experiencing one or more episodes of SE between January 1, 1991, and June 1,
      1995) were matched for age at follow-up to controls (88 children with symptomatic
      epilepsy without SE during that interval) and medical records were reviewed.
      Patients and controls did not differ in etiology or in age at epilepsy onset (1
      year 5 months [SD, 2 years 3 months] versus 1 year 3 months [SD, 1 year 5
      months]). Univariate analysis revealed significant associations between SE and
      several factors, including history of a first seizure as SE, partial epilepsy,
      partial seizures with secondary generalization, focal paroxysmal abnormalities
      and focal background abnormalities on EEG, and generalized abnormalities on
      neuroimaging. Groups did not differ in the proportion of patients on polypharmacy
      or with subtherapeutic serum antiepileptic drug levels, but there was a trend for
      greater use of phenobarbital in patients (57% versus 38%, odds ratio (OR) = 2.6,
      p = 0.057). With multiple logistic regression, four factors emerged as
      independent predictors of SE risk: focal background EEG abnormalities (OR = 6.51,
      p = 0.0005), partial seizures with secondary generalization (OR = 4.61, p =
      0.0021), first seizure as SE (OR = 3.99, p = 0.034), and generalized
      abnormalities on neuroimaging (OR = 2.85, p = 0.034). These four factors are
      indicators of a higher risk of SE in children with symptomatic epilepsy.

PMID- 9270592
TI  - Decreased postexercise facilitation of motor evoked potentials in patients with
      cerebellar degeneration.
AB  - We studied the effects of exercise on motor evoked potentials (MEPs) elicited by
      transcranial magnetic stimulation (TMS) in 18 normal (control) subjects and 11
      medication-free patients with cerebellar degeneration. Subjects performed
      repeated sets of isometric exercise of the extensor carpi radialis muscle until
      the muscle fatigued (subject became unable to maintain half maximal force). MEPs
      were recorded before and after each exercise set and for up to 30 minutes after
      the last set. The mean amplitude of MEPs recorded from the resting muscle
      immediately after each exercise set was 218% of the mean preexercise MEP
      amplitude in normal subjects and 132% in cerebellar patients, indicating
      postexercise MEP facilitation in both groups. However, postexercise MEP
      facilitation, compared with the mean preexercise MEP amplitude, was not
      significant in the patients but was significant in the normal subjects. The
      amplitudes of MEPs recorded within the first few minutes after fatigue were 44%
      of the mean preexercise MEP amplitudes in both groups. We conclude that in
      patients with cerebellar degeneration, postexercise MEP facilitation is
      significantly reduced, whereas postexercise MEP depression after fatigue is
      similar to that of normal subjects.

PMID- 9270593
TI  - Risk of serious cutaneous disorders after initiation of use of phenytoin,
      carbamazepine, or sodium valproate: a record linkage study.
AB  - Clinical and epidemiologic evidence suggest serious cutaneous reactions to
      antiepileptic drugs are more likely to occur during the first few months of use.
      However, studies have quantified risk for these reactions by including all users
      and their entire duration of use in denominator estimates possibly
      underestimating the risk. The objective of this study was to measure risk of
      serious cutaneous reactions in new users of phenytoin, carbamazepine, or valproic
      acid. We identified serious cutaneous reactions that included hospitalization and
      occurred within 60 days of the first or second prescription for new users of each
      study drug in the Saskatchewan Health data files. To classify outcome diagnoses,
      a dermatologist reviewed hospital discharge summaries. In 8,888 new phenytoin
      users there were eight serious cutaneous reactions. These included two probable
      and two possible cases of hypersensitivity syndrome, yielding a risk of 2.3 to
      4.5 per 10,000 for this syndrome. There were six serious cutaneous reactions in
      9,738 new carbamazepine users. These included one probable case and four possible
      cases of hypersensitivity syndrome, yielding a risk of 1 to 4.1 per 10,000 for
      this syndrome. There were no confirmed serious cutaneous diagnoses in 1,504 new
      valproate users. During the first few weeks of initiating therapy with phenytoin
      or carbamazepine, the clinician should be aware of the uncommon but not rare
      possibility that a cutaneous eruption could evolve into a significantly more
      serious reaction.

PMID- 9270594
TI  - An MRI study of autism: the cerebellum revisited.
AB  - We addressed the controversies surrounding the size of the neocerebellar vermis
      in autism and examined cerebellar size in light of recent reports of enlarged
      brain size in this disorder. In this study we use detailed MRI (1.5 mm) to
      examine the area of cerebellar lobules I through V and VI and VII and the volume
      of the total cerebellum in 35 autistic subjects and 36 controls. No abnormalities
      in the size of cerebellar lobules VI and VII in autistic individuals were
      detected, but the volume of the total cerebellum was significantly increased. We
      conclude that selective neocerebellar size abnormalities are not present in
      autistic individuals. Enlarged total cerebellar volume detected in this study is
      consistent with previous reports of regional brain enlargement in autism and also
      consistent with theories hypothesizing that the primary defect in autism is the
      result of abnormal development of a distributed neural network involving a number
      of regions of the brain.

PMID- 9270595
TI  - The D178N (cis-129M) "fatal familial insomnia" mutation associated with diverse
      clinicopathologic phenotypes in an Australian kindred.
AB  - Fatal familial insomnia (FFI) is an inherited prion disease characterized by
      progressive insomnia and dysautonomia with only modest cognitive impairment early
      in the disease, associated with atrophy and gliosis in the medial thalamus, but
      without spongiform change. FFI is associated with an aspartic acid to asparagine
      mutation at codon 178 of the PrP gene (D178N) in conjunction with methionine at
      the codon 129 polymorphic site on the mutant allele (cis-129M). We report a
      pedigree with this genotype in which marked clinicopathologic phenotypic
      heterogeneity occurred including typical Creutzfeldt-Jakob disease, FFI, and what
      was thought to be an autosomal dominant cerebellar ataxia (ADCA)-like-illness,
      suggesting that the genotype-phenotype correlation is not as tight for this
      mutation as is frequently supposed.

PMID- 9270596
TI  - The thigh may not be suitable as an injection site for patients self-injecting
      sumatriptan.
AB  - The objective of our study was to evaluate the differences between injection
      sites in the midthigh and the upper lateral quadrant of the gluteal area
      regarding the effect, depth of subcutaneous tissue, side effects, and patient
      preference in patients with cluster headache who self-inject 6 mg (0.5 ml) of
      sumatriptan. Our open, prospective clinical study was performed at the outpatient
      department of a Swedish university clinic. There were 19 male and one female
      subjects, 34 to 68 years old, suffering from cluster headache. We measured the
      subcutaneous tissue depth by ultrasound. Subjects performed four self-injections
      of sumatriptan, two in the thigh and two in the gluteal area. We evaluated the
      subcutaneous tissue depth from the skin surface to the muscle fascia, the effect
      on headache, side effects, and patient preference regarding the injection site.
      Subcutaneous tissue depth laterally in the thigh was 2 to 12 mm (median, 4 mm)
      and in the gluteal area was 34 to 68 mm (median, 45 mm). The needle of the self
      injector protrudes 5 to 6 mm. Forty thigh and 39 gluteal injections were
      recorded. The effect on headache was equal. Following injection in thigh the
      patients experienced more bleeding (p < 0.001, chi 2); local pain (p < 0.05, chi
      2); and a feeling of oppression in the head, neck, and chest area (p < 0.05, chi
      2); compared with injections in the gluteal area. Fifteen patients preferred the
      gluteal area as the injection site after the study, two patients had no
      preference, and three preferred the thigh. When using the self-injector in the
      lateral aspect of the thigh, intramuscular injection is liable to occur
      frequently in male patients. This may explain the differences in local and
      general side effects observed in this study. The upper lateral quadrant of the
      gluteal area is a more suitable injection site for male, and some female,
      patients when using the sumatriptan self-injector.

PMID- 9270597
TI  - Acetylcholine receptor autoantibody secretion by thymocytes: relationship to
      myasthenia gravis.
AB  - We tested thymus cells from 119 patients with acquired myasthenia gravis (MG) for
      in vitro production of acetylcholine receptor (AChR) binding antibodies (Ab); 109
      were seropositive, of which 82 (75%) secreted AChRAb in vitro. As noted in
      earlier studies, thymus cell secretion of AChRAb paralleled serum Ab levels (rho
      s = 0.503; p < 0.0001; n = 119). Striational Ab secretion also correlated with
      the patients' serologic status. AChRAb secretion in vitro predicted the secretory
      activity of thymus cells implanted in severe combined immune deficiency (SCID)
      mice. Thymocytes from patients treated with corticosteroids made significantly
      less AChRAb than thymocytes from untreated patients (p < 0.005). Of particular
      note: (1) AChRAb was secreted by thymocytes from two of five nonimmunosuppressed
      patients who had generalized MG but who were seronegative for AChR binding
      autoantibodies; and (2) AChRAb secretion from both thymic and nonthymic sources
      was documented in a patient with noninvasive thymoma whose first signs of MG
      appeared 7 months after thymectomy. We conclude that the thymus in a majority of
      patients with acquired MG is the principal but not the sole reservoir of
      immunocytes that specifically react with muscle antigens.

PMID- 9270598
TI  - Spinobulbar muscular atrophy can mimic ALS: the importance of genetic testing in
      male patients with atypical ALS.
AB  - The clinical presentation of amyotrophic lateral sclerosis (ALS) is variable and
      overlaps with that of other motor neuron diseases such as spinobulbar muscular
      atrophy (SBMA; Kennedy disease). With the identification of disease-specific
      mutations such as the CAG repeat expansion in the androgen receptor in SBMA, an
      accurate molecular diagnosis can be made in some patients with motor neuron
      disease. To determine the extent of misdiagnosis of ALS we screened 147 male ALS
      patients and 100 unrelated male patients from 100 familial ALS (FALS) kindreds
      for the presence of the SBMA mutation using polymerase chain reaction methods. We
      show that ALS was clinically misdiagnosed in 2% of sporadic cases and in two of
      the 100 FALS kindreds. This study underscores the difficulty in distinguishing
      SBMA from ALS clinically, particularly in patients who lack the classic signs of
      each disease.

PMID- 9270599
TI  - Longitudinal study of fiber density and motor unit number estimate in patients
      with amyotrophic lateral sclerosis.
AB  - We examined fiber density, compound muscle action potential (CMAP) amplitude, and
      motor unit number estimate (MUNE) of the abductor digiti minimi and grip strength
      longitudinally. We sought to determine the effects of ALS on these measurements
      and to evaluate which of these tests may be more sensitive in evaluating
      progression of ALS and possibly predicting survival. Ten patients were examined
      at months 0, 3, and 6. A significant decrease in MUNE and increase in fiber
      density were observed at months 3 and 6 (p < 0.02) compared with baseline (month
      0). Mean CMAP and grip strength declined, but not significantly. The decrease in
      MUNE over 6 months was significantly greater than that of CMAP and grip strength
      (p < 0.025). The significant changes in MUNE and fiber density over time suggest
      that they are more sensitive in measuring the rate of progression of ALS. To
      evaluate further the utility of these tests, we arbitrarily divided the patients
      into equal groups based on length of survival. MUNE declined significantly in the
      group with shorter survival (p < 0.01). Conversely, fiber density increased
      significantly in patients with longer survival (p < 0.01). With similar
      statistical analysis there were no significant differences in decline of CMAP or
      grip strength in either subgroup over 6 months. Our study suggests that MUNE and
      fiber density are more sensitive than CMAP and grip strength in detecting
      progression of ALS. Furthermore, we raise the hypotheses that a greater increase
      in fiber density identifies a group of patients with ALS who will have longer
      survival, and that a greater decline in MUNE identifies a group with a worse
      prognosis.

PMID- 9270600
TI  - Deficiency of syntrophin, dystroglycan, and merosin in a female infant with a
      congenital muscular dystrophy phenotype lacking cysteine-rich and C-terminal
      domains of dystrophin.
AB  - Primary deficiency of merosin is the cause of the classic form of congenital
      muscular dystrophy (CMD) accompanied by brain white matter abnormalities. We
      report a female infant with dystrophinopathy who was deficient in merosin in
      skeletal muscle. The patient had a phenotype of typical CMD and white matter
      abnormalities on brain MRI. Merosin was greatly reduced in the biopsied skeletal
      muscle. However, the expression of dystroglycan and syntrophin was also greatly
      reduced, and the immunoreactivity for the antibodies against the cysteine-rich/C
      terminal domains of dystrophin was absent in the sarcolemma. Reverse
      transcriptase polymerase chain reaction analysis of the dystrophin gene revealed
      a complete lack of exons 71 through 74. In skeletal muscle, only the mutant gene
      was expressed. These results suggest that the patient is a symptomatic Duchenne
      muscular dystrophy carrier with skewed X-inactivation. This patient illustrates
      for the first time that a dystrophin abnormality can cause a secondary deficiency
      of merosin in dystrophinopathy. The reduction of merosin may account for the
      clinical phenotype of CMD and correlate with the white matter abnormalities in
      our patient.

PMID- 9270601
TI  - alpha-Tocopherol transfer protein gene: exon skipping of all transcripts causes
      ataxia.
AB  - This report concerns the characterization of the alpha-tocopherol transfer
      protein (alpha-TTP) gene in a Japanese family affected by ataxia with isolated
      vitamin E deficiency (AVED). The sequence analysis revealed a G-to-A transition
      at the 3' end of exon 3 in both alleles, which predicts outsplicing of this exon
      from premessenger RNA and the concomitant frame shift in the ataxic patient. We
      used reverse transcriptase-polymerase chain reaction to analyze alpha-TTP gene
      transcripts. All transcripts in peripheral blood lymphocytes of the AVED patient,
      who was treated with large doses of vitamin E, lacked exon 3. The deduced
      truncated protein shares only 43% of the normal alpha-TTP. Normal control tissues
      and cells contained normal transcripts and, unexpectedly, also the same mutant
      transcripts as those of the patient, although with different transcription
      levels. Treatment of normal fibroblasts with clinically relevant concentrations
      of vitamin E increased production of transcripts in a dose-dependent manner. We
      propose that exon skipping of all transcripts through the complete inactivation
      of the splice site accounts for the clinical onset of AVED and for the clinical
      resistance to vitamin E in our patient.

PMID- 9270602
TI  - A mitochondrial DNA tRNA(Val) point mutation associated with adult-onset Leigh
      syndrome.
AB  - Subacute necrotizing encephalomyelopathy (Leigh syndrome) is associated with a
      number of mitochondrial DNA (mtDNA) abnormalities. We studied a family with
      maternally inherited encephalomyelopathy. Two siblings developed adult-onset
      Leigh syndrome. Muscle biopsy specimens showed enhanced succinic dehydrogenase
      activity and cytochrome oxidase-negative fibers. We sequenced the ATPase- and
      transfer RNA (tRNA)-encoding genes of mtDNA and identified a novel mtDNA valine
      tRNA mutation at base pair 1644. This transversion was heteroplasmic in blood and
      muscle in all individuals studied, and the proportion of mutant mtDNA correlated
      with disease severity. This is the first heteroplasmic transversion within a
      mtDNA tRNA gene and the second pathogenic mtDNA tRNA(Val) mutation to be
      associated with human disease.

PMID- 9270604
TI  - Leigh syndrome associated with the T9176C mutation in the ATPase 6 gene of
      mitochondrial DNA.
AB  - A child with clinical and neuroradiologic evidence of Leigh syndrome (LS) had the
      T-to-C transition at nt 9176 in the ATPase 6 gene of mtDNA. The mutation was
      homoplasmic in muscle and maternally inherited. The proband's mother had ataxia
      and harbored 93% of mutant genomes in blood, whereas three clinically unaffected
      maternal relatives had varying degrees of heteroplasmy in blood. These data
      confirm the association of the T9176C mutation with LS and extend the clinical
      heterogeneity of mutations in the ATPase 6 gene.

PMID- 9270603
TI  - Detection of 14-3-3 protein in the CSF of genetic Creutzfeldt-Jakob disease.
AB  - The 14-3-3 protein, a protein involved in signal transduction, is present in the
      CSF of patients with Creutzfeldt-Jakob disease (CJD) and not in patients with
      other dementing diseases. We show here that this is also true for patients with
      E200K CJD, but not for healthy carriers of the mutation.

PMID- 9270605
TI  - A new mitochondrial DNA mutation associated with mitochondrial myopathy:
      tRNA(Leu)(UUR) 3254C-to-G.
AB  - We investigated a patient with mitochondrial myopathy accompanied by
      cardiomyopathy. Molecular analysis disclosed a C-to-G substitution at nucleotide
      position 3254 of the mitochondrial tRNA(Leu)(UUR). Pedigree analysis revealed
      that this mutation was inherited maternally. Mutation C3254G may also be a
      candidate for genetic defects in mitochondrial myopathy.

PMID- 9270606
TI  - Autosomal dominant transmission of Dejerine-Sottas disease (HMSN III).
AB  - Hereditary motor-sensory neuropathy type III (HMSN III) (Dejerine-Sottas disease)
      is a severe demyelinating neuropathy that is traditionally considered autosomal
      recessive. We report a father and daughter diagnosed with HMSN III by clinical,
      electrophysiologic, and pathologic criteria, thus showing that it may be
      transmitted in an autosomal dominant fashion in selected families.

PMID- 9270607
TI  - Machado-Joseph disease: cerebellar ataxia and autonomic dysfunction in a patient
      with the shortest known expanded allele (56 CAG repeat units) of the MJD1 gene.
AB  - We describe an unusual case of a patient with Machado-Joseph disease (MJD) who
      showed autonomic dysfunctions in addition to cerebellar ataxia. The number of CAG
      repeat units in the expanded allele of the MJD1 gene of the patient is smaller
      (56 CAG repeat units) than all previously reported numbers of CAG repeat units in
      expanded alleles. Thus, the findings in this patient indicate that the clinical
      features of MJD cover a wider spectrum than previously thought.

PMID- 9270608
TI  - Somatic mosaicism for Friedreich's ataxia GAA triplet repeat expansions in the
      central nervous system.
AB  - Most patients with Friedreich's ataxia (FRDA) carry expanded GAA repeats in both
      homologues of the frataxin gene on chromosome 9. We determined the size of the
      GAA repeats in autopsied samples from the CNS of six FRDA patients. We observed
      heterogeneity of repeat sizes in different CNS regions, indicative of extensive
      mitotic instability. Samples from the same CNS subdivision (e.g., cortex,
      thalamus) contained a similar mixture of alleles, suggesting that the pattern of
      repeat size mosaicism reflects the developmental history of each sample. Regional
      differences in repeat size could not account for the characteristic distribution
      of pathology in FRDA, which appears instead to be related to the pattern of
      frataxin expression.

PMID- 9270609
TI  - Neuronal loss and plasticity in the supraoptic nucleus in Parkinson's disease.
AB  - Disturbed circadian control of renal water excretion and blood pressure
      adaptation in Parkinson's disease (PD) suggest impaired hypothalamic
      magnocellular neurosecretion. To test the hypothesis that this may relate to
      specific hypothalamic pathology in PD, we studied morphometrically the neuronal
      population of the supraoptic nucleus (SON) in PD patients and controls. Neuronal
      loss in the SON of PD patients was associated with increased somatic, nuclear,
      and nucleolar size of remaining neurons, suggesting compensatory response of
      these cells. We conclude that SON pathology is a feature of PD and may account
      for specific signs of neurohumoral dysfunction.

PMID- 9270610
TI  - Migraine association and linkage studies of an endothelial nitric oxide synthase
      (NOS3) gene polymorphism.
AB  - Migraine shows strong familial aggregation. However, the number of genes involved
      in the disorder is unknown and not identified. Nitric oxide is involved in the
      central processing of pain stimuli and plays an important role in the regulation
      of basal or stimulated vasodilation. Nitric oxide synthase, which controls the
      synthesis of nitric oxide, could possibly be a cause, or candidate gene, in
      migraine etiology. In this study, we detected a polymorphism for endothelial
      nitric oxide synthase by polymerase chain reaction and tested this for
      association and linkage to migraine. Results from the study did not show an
      association of the nitric oxide synthase microsatellite when tested in 91
      affected and 85 unaffected individuals. Using the FASTLINK program for parametric
      linkage analysis, the polymorphism did not show significant linkage to migraine
      when tested in four migraine pedigrees composed of 116 individuals, 52 affected.
      Total LOD scores excluded linkage up to 8.5 cM between the nitric oxide synthase
      polymorphism and migraine. Results using the nonparametric affected pedigree
      member form of analysis also did not support a role for this gene in migraine
      etiology.

PMID- 9270611
TI  - Intra-arterial thrombolysis of embolic proximal middle cerebral artery occlusion
      from presumed atrial myxoma.
AB  - The role of thrombolysis in brain ischemia in patients with atrial myxoma is
      unknown. A patient with acute brain ischemia and previously undiagnosed atrial
      myxoma recanalized an occluded middle cerebral artery with intra-arterial
      thrombolysis. Arterial occlusion from presumed myxoma may be amenable to
      fibrinolysis. Angiography before treatment in patients with atrial myxoma
      excludes a myxomatous pseudoaneurysm and permits site-specific thrombolytic
      instillment.

PMID- 9270612
TI  - Treatment of multiple cerebral emboli from an ulcerated, thrombogenic ascending
      aorta with aortectomy and graft replacement.
AB  - Multiple studies link aortic arch atheroma as a donor site for cerebral emboli.
      However, treatment of this condition remains controversial. We report a patient
      with recurrent brain emboli from an ulcerated, thrombogenic aorta treated with
      aortectomy and graft replacement.

PMID- 9270613
TI  - Autoimmune thyroiditis and a rapidly progressive dementia: global hypoperfusion
      on SPECT scanning suggests a possible mechanism.
AB  - We report the clinical, laboratory, EEG, and SPECT findings in a 59-year-old
      euthyroid woman with previously undiagnosed autoimmune thyroiditis, subclinical
      hypothyroidism, and rapidly progressive dementia. We made a diagnosis of
      Hashimoto's encephalopathy based on elevated thyrotropin, abnormal EEG, and
      clinical improvement after thyroid hormone replacement. SPECT demonstrated global
      hypoperfusion with normalization on clinical recovery, suggesting a possible
      mechanism for the pathogenesis of Hashimoto's encephalopathy.

PMID- 9270614
TI  - A population-based case-control study of the tumor necrosis factor alpha-308
      polymorphism in multiple sclerosis.
AB  - Tumor necrosis factor alpha (TNF alpha) expression is enhanced in patients with
      active MS and other inflammatory diseases. A guanine-to-adenine polymorphism at
      position -308 of the TNF alpha promoter region (the TNF2 allele) is associated
      with increased TNF alpha expression. We evaluated 110 MS patients derived from an
      Olmsted County, MN, prevalence study. Three other patient cohorts (autoimmune,
      serious infectious illness, and other neurologic diseases) and matched controls
      were derived from a Mayo Clinic DNA bank. We used polymerase chain reaction
      amplification of specific alleles to screen for the TNF2 allele and to determine
      zygosity. We found one homozygote and 29 heterozygotes in the MS patients. There
      was no association between the presence of the TNF2 allele and MS or the other
      disease categories by matched-pair and group analyses.

PMID- 9270615
TI  - What's in a name? Dr. Lewey and the Lewy body.

PMID- 9270616
TI  - Magnetic resonance imaging in a patient with segmental zoster paresis.

PMID- 9270617
TI  - Cerebral hemorrhage in a patient taking fenfluramine and phentermine for obesity.

PMID- 9270618
TI  - Interleukin-2 therapy does not exacerbate multiple sclerosis.

PMID- 9270619
TI  - Perimesencephalic nonaneurysmal subarachnoid hemorrhage: first hint of a cause?

PMID- 9270621
TI  - Psychogenic status epilepticus.

PMID- 9270620
TI  - Neurology's witness to history.

PMID- 9270622
TI  - Genomic imprinting in Tourette's syndrome.

PMID- 9270623
TI  - Headache classification.

PMID- 9270624
TI  - Lupus anticoagulant and chorea.

PMID- 9270625
TI  - Foot dipping in coma.

PMID- 9270626
TI  - Treatment of multiple sclerosis with interferon beta-1 b.

PMID- 9270627
TI  - Paroxysmal kinesigenic choreoathetosis.

PMID- 9270629
TI  - Neurogenetics and primary care.

PMID- 9270628
TI  - Physostigmine and Alzheimer's disease.

PMID- 9270630
TI  - A profile of candidates for repeat myocardial revascularization: implications for
      selection of treatment.
AB  - OBJECTIVES: It is not known whether the results of randomized trials comparing
      coronary artery bypass grafting to percutaneous transluminal coronary angioplasty
      for initial revascularization apply to repeat revascularization in patients with
      prior bypass grafts. We studied the differences between the patients with prior
      bypass grafts referred for surgery or angioplasty to identify the clinical and
      angiographic characteristics that correlated best with either choice and to find
      clues that might aid in selecting one treatment over the other. METHODS: Between
      1992 and 1994, 870 patients underwent first isolated reoperation and 793 patients
      underwent first balloon angioplasty after a previous operation. A jeopardy score
      (0 to 8 points) was derived for each patient on the basis of the relative size of
      the ischemic territory. Clinical and angiographic data were analyzed for
      association with the revascularization strategy. RESULTS: The following
      characteristics were more prevalent in the reoperation group: male sex, diabetes,
      hypertension, valvular disease, normocholesterolemia, and severe left ventricular
      systolic dysfunction; fewer functioning venous and arterial grafts; and a higher
      jeopardy score (p < 0.01 for all) than in the angioplasty group. A higher
      jeopardy score, diabetes, and a lower number of functioning arterial or venous
      grafts were strong, independent predictors of referral for reoperation (p < 0.01
      for all). In hospital death and Q-wave infarction (p < 0.01 for both) were more
      frequent in the reoperation group. CONCLUSIONS: Reoperation was the
      revascularization procedure of choice when larger regions of myocardium were in
      jeopardy. Angioplasty was more frequently chosen in the presence of a patent
      arterial graft to the left anterior descending coronary artery or multiple
      functioning bypass grafts. Reoperation was associated with a higher risk of in
      hospital complications than angioplasty.

PMID- 9270631
TI  - Cardiac surgery in a high-risk group of patients: is prolonged postoperative
      antibiotic prophylaxis effective?
AB  - OBJECTIVE: In a prospective, randomized study, postoperatively prolonged
      antibiotic prophylaxis is evaluated in a high-risk group of patients undergoing
      cardiac operations. These patients had postoperative low cardiac output
      necessitating inotropic support and intraaortic balloon pumping. METHODS: Between
      January 1991 and 1994, 53 patients were enrolled in the study (42 men, mean age
      65 years). All patients received the usual perioperative (24 hours) cefazolin
      prophylaxis. In the study group (n = 28) a prolonged regimen of prophylaxis with
      ticarcillin/clavulanate was performed for 2 days and vancomycin was added in a
      low dose until removal of the intraaortic balloon pump. The control group (n =
      25) did not receive a prolonged regimen of prophylaxis. Follow-up ended at
      hospital discharge. RESULTS: Early mortality was 7 of 28 patients (25%) in the
      prophylaxis group and 8 of 25 patients (32%) in the control group (p = 0.397).
      Defined infections (pneumonia, n = 22; sepsis, n = 8; deep sternal wound
      infection, n = 2) occurred in 50% of the study group and 68% of the control group
      (p = 0.265). In all patients with septicemia, only coagulase-negative
      staphylococci could be isolated from the bloodstream (5 patients in the
      prophylaxis group vs 3 in the control group). Infectious parameters were
      controlled daily and did not differ significantly between groups. A total of 1158
      bacteriologic tests were performed (blood cultures, n = 389; intravascular
      catheters, n = 208; bronchial aspirates, n = 411; intraaortic balloon pumps, n =
      42; wound secretions, n = 108) showing bacterial growth in 322 (28%) without a
      significant difference between the groups. In the prophylaxis group, 13
      intravascular catheters and intraaortic balloon pumps showed bacterial growth
      versus 11 in the control group. No side effects were seen. CONCLUSIONS: In a high
      risk group of patients undergoing cardiac operations, infectious outcome could
      not be effectively influenced by an additional and prolonged postoperative
      prophylaxis regimen with low-dose vancomycin and ticarcillin/clavulanate. Low
      dose vancomycin did not reduce the rate of infections or colonizations of
      intravascular catheters with gram-positive organisms.

PMID- 9270632
TI  - Dynamic cardiomyoplasty: its chronic and acute effects on the failing heart.
AB  - OBJECTIVES: Dynamic cardiomyoplasty is an alternative therapy for end-stage heart
      failure. We investigated the mechanisms, both acute and chronic, by which a
      synchronously stimulated conditioned muscle wrap affects left ventricular
      function in a chronic canine model of dilated cardiomyopathy. METHODS: Nineteen
      dogs underwent rapid ventricular pacing at a rate of 215 beats/min for 4 weeks to
      create a model of heart failure. Eight dogs were then randomly selected to
      undergo cardiomyoplasty, and all dogs received 6 additional weeks of rapid
      ventricular pacing. The cardiomyoplasty group also received a graded muscle
      conditioning protocol of synchronized burst stimulation to transform the muscle
      wrap. All dogs were studied with pressure-volume analysis and echocardiography at
      baseline and after 4 and 10 weeks of rapid ventricular pacing. Data in the
      cardiomyoplasty group were analyzed with the stimulator off, with it augmenting
      every beat (1:1), and with it augmenting only every other beat (1:2). RESULTS:
      Stimulator "of" data at 10 weeks of rapid pacing demonstrated chronic effects by
      enhanced ventricular function (end-systolic elastance = 1.80 after myoplasty vs
      1.17 for controls, p = 0.005) and a stabilization of volumes and composite end
      systolic and end-diastolic pressure-volume relations in the cardiomyoplasty group
      when compared with controls. Myoplasty stimulation increased apparent
      contractility (preload recruitable stroke work = 31.3 for stimulator "of" vs 40.6
      for stimulator 1:2 assisted beats [p < 0.05] and vs 45.4 for stimulator 1:1 [p <
      0.05]). CONCLUSIONS: Benefits from dynamic cardiomyoplasty are by at least two
      mechanisms: (1) the girdling effects of a conditioned muscle wrap, which halts
      the chronic remodeling of heart failure, and (2) active systolic assistance,
      which augments the apparent contractility of the failing heart.

PMID- 9270633
TI  - Outcome of atrial fibrillation after mitral valve repair.
AB  - OBJECTIVE: The aim of the study was to evaluate the prognostic factors for return
      to sinus rhythm after mitral valve repair. METHOD: One hundred ninety-one
      patients underwent surgery for mitral valve repair, including 142 procedures for
      valve repair only (74%). The patients with preoperative atrial fibrillation
      (50.5%) were older, clinically more symptomatic, and had a greater degree of left
      atrial dilation than the patients who had sinus rhythm. RESULTS: Preoperative
      cardiac rhythm, the duration of preoperative atrial fibrillation, and a lesser
      degree of left atrial hypertrophy are significant prognostic factors independent
      of the maintenance of sinus rhythm. The probability of return to stable sinus
      rhythm was 93.7% when sinus rhythm was already present before the operation and
      80% when atrial fibrillation was intermittent or of less than 1 year's duration;
      probability declined abruptly for durations over 1 year. No significant
      difference in patient survival was noted between those who had sinus rhythm (99%
      +/- 0.9% at 1 year and 86% +/- 6.6% at 5 years) and those who had atrial
      fibrillation in the preoperative period (95% +/- 3.1% at 1 year and 86% +/- 8.4%
      at 5 years). In contrast, the postoperative return to sinus rhythm was associated
      with 99% +/- 0.9% and 94% +/- 4.8% survivals at 1 and 4 years versus 97% +/- 1.5%
      and 77% +/- 13% in the event of postoperative atrial fibrillation. CONCLUSION:
      The aim of restoring postoperative sinus rhythm after mitral valve repair should
      lead to surgery being conducted on patients who have sinus rhythm or recent-onset
      atrial fibrillation. Surgery for atrial fibrillation may be of value in patients
      with a long history of atrial fibrillation, providing that it does not induce
      prohibitive excess mortality.

PMID- 9270634
TI  - Mature pulmonary lobar transplants grow in an immature environment.
AB  - OBJECTIVE: Mature lobar transplantation will increase the pediatric donor organ
      pool, but it remains unknown whether such grafts will grow in a developing
      recipient and provide adequate long-term support. We hypothesized that a mature
      pulmonary lobar allograft implanted in an immature recipient would grow. METHODS:
      We investigated our hypothesis in a porcine orthotopic left lung transplant model
      using animals matched by the major histocompatibility complex to minimize the
      effects of chronic rejection. Twenty-three immature animals (< 12 weeks of age
      and < 10 kg total body weight) received either sham left thoracotomy (SH control,
      n = 4), left upper lobectomy to study compensatory growth (UL control, n = 4),
      age-matched immature whole left lung transplants (IWL TXP, n = 6), mature (donor
      > 1 yr in age and > 40 kg in total body weight) left lower lobe transplants (MLL
      TXP, n = 5), or mature left upper lobe transplants (MUL TXP, n = 4). Twelve weeks
      after implantation, functional residual capacity of the left lung was measured
      and arterial blood gas samples were obtained after the native right lung had been
      excluded. The graft was excised and weighed, and samples for microscopy and
      wet/dry ratios were collected. RESULTS: Initial and final graft weights were as
      follows: IWL TXP group (34.6 +/- 1.5 and 107.8 +/- 5.9 gm, p < 0.0001), MLL TXP
      group (72.4 +/- 6.8 and 111.4 +/- 8.7, p < 0.001), and MUL TXP group (32.8 +/-
      1.3 and 92.8 +/- 7.1 gm, respectively, p < 0.004). No significant differences
      between groups were demonstrated when functional residual capacity, wet/dry
      ratios, or oxygenation were compared. Immunohistochemical staining for the
      nuclear antigen Ki-67 demonstrated dividing pneumocytes. CONCLUSIONS: We conclude
      that a mature lobar graft implanted into an immature recipient grows by
      pneumocyte division in this model. Mature lobar transplants can be expected to
      grow and provide adequate long-term function in developing recipients.

PMID- 9270635
TI  - Risk factors for the development of bronchiolitis obliterans syndrome after lung
      transplantation.
AB  - OBJECTIVE: This study identifies specific clinical and immunologic factors in
      lung transplant recipients that influence the subsequent development of chronic
      allograft dysfunction. METHODS: The study group consisted of 132 consecutive
      patients who received lung allografts (76 single, 25 bilateral single, and 31
      heart-lung) and survived at least 90 days. One hundred twenty-one patients were
      used in the analysis that modeled time to development of histologic obliterative
      bronchiolitis or bronchiolitis obliterans syndrome. RESULTS: Variables noted to
      have an effect on the time to development of bronchiolitis obliterans syndrome
      included cytomegalovirus pneumonitis (RR = 3.2, p = 0.001), late acute rejection
      (RR = 1.3, p = 0.02), human leukocyte antigen mismatches at the A loci (RR = 1.8,
      p = 0.02), total human leukocyte antigen mismatches (RR = 1.4, p = 0.04), and
      absence of donor antigen-specific hyporeactivity (52% vs 100% survival free from
      bronchiolitis obliterans syndrome at 2 years; p = 0.005). Cytomegalovirus
      pneumonitis had a significant effect on time to obliterative bronchiolitis (RR =
      3.6, p = 0.0005), as did donor antigen-specific hyporeactivity (52% vs 100%
      survival free from obliterative bronchiolitis at 2 years; p = 0.01). In
      multivariate analysis, cytomegalovirus pneumonitis (RR = 3.2, p = 0.02), human
      leukocyte antigen mismatches at the A loci (RR = 2.4, p = 0.006), and late acute
      rejection (RR = 1.3, p = 0.02) were identified as predictors of bronchiolitis
      obliterans syndrome. Cytomegalovirus pneumonitis was associated with time to
      development of histologic obliterative bronchiolitis (RR = 2.3, p = 0.02).
      CONCLUSIONS: Several risk factors were associated with the development of chronic
      allograft dysfunction, which, in turn, had a significant impact on long-term
      survival. Early identification of lung allograft recipients with risk factors for
      the development of bronchiolitis obliterans syndrome may allow modification in
      immunosuppression and antiviral therapy to potentially decrease the prevalence of
      this disorder.

PMID- 9270636
TI  - Editorial on combined therapy for squamous cell carcinoma of the esophagus.

PMID- 9270638
TI  - Preoperative chemotherapy versus surgical therapy alone for squamous cell
      carcinoma of the esophagus: a prospective randomized trial.
AB  - OBJECTIVE: This study investigated the role of preoperative chemotherapy in
      squamous cell cancer of the esophagus. METHODS: A prospective randomized trial
      was undertaken in 147 patients: 74 received preoperative chemotherapy comprising
      cisplatin and 5-fluorouracil and 73 had surgical therapy alone. End points were
      cancer and therapy-related deaths. RESULTS: Sixty-six patients (89%) in the
      chemotherapy group underwent resection compared with 69 (95%) in the control
      group (p = not significant). Of the 60 patients who had resection after
      completing the chemotherapy program, 35 (58%) had a significant response, of whom
      four (6.7%) had a complete pathologic response. Postoperative mortality rates
      were 8.3% and 8.7% in the chemotherapy and control groups, respectively (p = not
      significant). Significant downstaging was evident with chemotherapy; curative
      resections were possible in 67% of these patients compared with 35% in the
      control group (p = 0.0003). T3 and T4 tumors were found in 67% and 91% of the
      chemotherapy and control groups, respectively (p = 0.0002). The respective
      figures for N1 disease were 70% and 88% (p = 0.009). An intent-to-treat analysis
      of survival showed no significant difference between the two groups. Median
      survivals were 16.8 and 13 months, respectively (p = 0.17). Of those who
      completed the chemotherapy and resection, responders fared better than control
      patients. Median survivals were 42.2 months and 13.8 months, respectively (p =
      0.003). Median survival (8.3 months) was worse for nonresponders than for control
      patients (p = 0.03). The recurrence pattern suggested a significant reduction in
      locoregional disease with chemotherapy. CONCLUSIONS: Preoperative chemotherapy
      was safe and resulted in significant downstaging and an increased likelihood of
      curative resection. Survival was not better than that in the surgery-alone group,
      but responders did fare better than nonresponders.

PMID- 9270637
TI  - A randomized trial of surgery with and without chemotherapy for localized
      squamous carcinoma of the thoracic esophagus: the Japan Clinical Oncology Group
      Study.
AB  - OBJECTIVE: To determine whether postoperative adjuvant chemotherapy confers a
      survival benefit on patients with esophageal squamous cell carcinoma undergoing
      radical surgery, we undertook a cooperative, prospective randomized controlled
      trial. METHODS: A total of 205 patients underwent transthoracic esophagectomy
      with lymphadenectomy at eleven institutions between December 1988 and July 1991.
      These patients were prospectively randomized into two groups (100 patients
      underwent surgery alone and 105 patients had additional two courses of
      combination chemotherapy with cisplatin (70 mg/m2) and vindesine (3 mg/m2). The
      two groups did not differ with respect to sex, age, location of tumor, and
      distributions of pT, pN, pM, or p stage. RESULTS: The 5-year survival was 44.9%
      in the surgery alone group and 48.1% in the surgery plus chemotherapy group. The
      relative risk was estimated to be 0.89 (95% confidence interval, 0.61 to 1.31) in
      the surgery plus chemotherapy group compared with the surgery alone group. No
      significant differences in survival were detected between the two groups, even
      with lymph node stratification. CONCLUSION: Postoperative adjuvant chemotherapy
      with cisplatin and vindesine has no additive effect on survival in patients with
      esophageal cancer compared with surgery alone.

PMID- 9270639
TI  - New-generation valved conduit: an experimental study.
AB  - OBJECTIVE: An ideal valved conduit to repair complex congenital heart defects is
      yet to be developed. In this study we have evaluated the merits of our newly
      developed calcification-free biologic valve incorporated in a compatible conduit
      of biologic origin in an animal model. METHODS: Porcine aortic valves and main
      pulmonary arteries were cross-linked in glutaraldehyde, followed by coupling to
      partially degraded heparin through an intermediate surface-bound substrate
      containing amino groups. Because commercially available valves are treated only
      with glutaraldehyde, control aortic valves and main pulmonary arteries were cross
      linked in 0.625% glutaraldehyde. Valved conduits were fabricated from main
      pulmonary arteries, which were sewn to the aortic and ventricular ends of aortic
      valves. Valved conduits were examined for calcification and other pathologic
      changes after being implanted in the descending thoracic aorta in juvenile sheep
      for 5 months. RESULTS: Severe calcification was noticed in all layers of cusps
      (calcium, 231.86 +/- 17.90 mg/gm) and aortic wall (calcium, 123.24 +/- 24.72
      mg/gm) of aortic valves and main pulmonary arteries (calcium, 135.43 +/- 26.63
      mg/gm) of valved conduits treated with 0.625% glutaraldehyde. Cusps (calcium,
      1.28 +/- 0.22 mg/gm) of the aortic valve of heparin-bonded conduits did not
      calcify at all. Only sparse calcific deposits were noticed in the medial layer of
      the aortic wall (calcium, 25.90 +/- 22.79 mg/gm) of aortic valves and main
      pulmonary arteries (calcium, 9.64 +/- 10.79 mg/gm) of the valved conduits coupled
      to heparin. CONCLUSION: Heparin coupling is effective in preventing calcification
      of glutaraldehyde cross-linked valved conduits implanted in the systemic
      circulation of juvenile sheep.

PMID- 9270641
TI  - Intravenous co-infusion of adenosine and norepinephrine.

PMID- 9270640
TI  - Use of a bovine jugular vein graft with natural valve for right ventricular
      outflow tract reconstruction: a one-year animal study.
AB  - OBJECTIVE: We evaluated a bovine jugular vein graft with a natural trileaflet
      valve for right ventricular outflow tract reconstruction in a canine study for an
      entire year. METHODS: Heparinized bovine jugular vein grafts with a natural valve
      cross-linked with a hydrophilic polyepoxy compound of 18 to 20 mm in internal
      diameter were implanted in the right ventricular-pulmonary arterial position in
      eight dogs, and the main natural pulmonary artery was ligated. Anticoagulants
      were not used after implantation. Five grafts were retrieved on day 182 after
      implantation and the other three grafts on days 196, 375, and 385, respectively,
      and were inspected by macroscopic and microscopic observation. Cardiac
      catheterization, followed by angiography and echocardiography, was done just
      before graft retrieval. RESULTS: No graft kinking or regurgitation of the valve
      was observed. Echocardiography showed natural valve motion without thickening of
      the leaflets. Blood pressure in the conduits ranged from 18/9 to 31/4 mm Hg, in
      the right ventricle from 18/4 to 40/0 mm Hg, and the gradient varied from 0 to 14
      mm Hg. The explanted conduits maintained their original shape, softness, and
      pliability with good coaptation of valves, without calcification or degenerative
      changes, except for one leaflet with slight deformation. In microscopic
      observation, endothelial cells lined the luminal surface of the conduit except
      for the areas adjacent to the valve. CONCLUSION: The graft worked perfectly as a
      right ventricular-pulmonary arterial valved conduit without anticoagulant therapy
      for a long time.

PMID- 9270642
TI  - Intravenous co-infusion of adenosine and norepinephrine preconditions the heart
      without adverse hemodynamic effects.
AB  - OBJECTIVE: A simple intervention is needed that could protect the heart against
      infarction during limited-access coronary artery bypass grafting. Adenosine and
      norepinephrine can precondition the heart with resulting protection, but adverse
      hemodynamic effects prevent clinical application. Because heart rate, blood
      pressure, and contractility effects of these two drugs are diametrically
      opposite, a mixture might be beneficial. METHODS: A superficial branch of the
      left coronary artery of rabbits was surrounded with a suture. Infarction was
      produced in all hearts by a 30-minute coronary artery occlusion. Infarct size
      after reperfusion was measured and is presented as a percentage of the risk zone.
      The effect of 5-minute intravenous co-infusion of adenosine (20 mg/kg) and
      norepinephrine (0.1 mg/kg) 15 minutes before ischemia was examined. In addition,
      the protective effect of three sequential intravenous bolus injections of
      adenosine at either 0.2 or 0.4 mg/kg was evaluated. RESULTS: Thirty minutes of
      regional ischemia caused infarction of 40% +/- 4% of the risk zone. The
      combination of adenosine and norepinephrine caused no change in blood pressure
      but rather protected the heart, with infarction of only 9% +/- 2% of the risk
      zone (p = 0.0001 vs control). Adenosine-norepinephrine co-infusion still
      protected the heart when the interval between infusion and ischemia was extended
      to 60 minutes, but it did not protect with a 120-minute interval. Intravenous
      bolus injections of adenosine resulted in cardiac slowing and marked hypotension.
      Boluses of 0.2 mg/kg resulted in a minimal, but significant, reduction in infarct
      size, whereas the higher dose provided no protection. CONCLUSION: Adenosine
      norepinephrine co-infusion provides a feasible and safe parenteral method for
      preconditioning the heart.

PMID- 9270643
TI  - Organ perfusion with Hemopump device assistance with and without intraaortic
      balloon pumping.
AB  - OBJECTIVE: Our objective was to analyze the potential advantage of combining an
      intraaortic balloon pump with a transthoracic Hemopump device (Medtronic, Inc.,
      Minneapolis, Minn.) (Nimbus Medical, Inc., Rancho Cordova, Calif.). METHODS:
      Twelve sheep underwent implantation of a transthoracic Hemopump device and an
      intraaortic balloon pump. In the first series (n = 6), we analyzed the influence
      of the counterpulsation on the performance of the Hemopump device. In the second
      group (n = 6), hemodynamic changes, myocardial wall thickening, organ perfusion,
      and myocardial perfusion (determined with colored microspheres) were analyzed
      under the following conditions: (1) control situation, (2) during application of
      coronary stenosis, (3) during support with the Hemopump device, and (4) during
      support with the Hemopump device combined with intraaortic balloon pump support.
      RESULTS: In the first series, we found that addition of counterpulsation reduced
      output with the Hemopump device by 11.1% +/- 6%. In the second series, it was
      shown that coronary stenosis significantly reduced contractility (rate of
      pressure change and wall thickening) but did not cause hemodynamic collapse.
      Myocardial blood flow was significantly reduced in the poststenotic
      subendocardial regions (mean subendocardial blood flow dropped from 78 +/- 33 to
      24 +/- 17 ml/min/100 gm; p = 0.0486). Support with the Hemopump device alone
      improved the ratio of subendocardial to subepicardial blood flow, but endocardial
      underperfusion remained (analysis of variance, p < 0.001). The Hemopump device
      with an intraaortic balloon pump completely restored perfusion in poststenotic
      regions. Peripheral organ perfusion did not change during ischemia or mechanical
      support. CONCLUSIONS: The association of balloon counterpulsation with the
      Hemopump device reduces the Hemopump output by 11% and increases myocardial blood
      flow to ischemic regions. Perfusion to peripheral organs remains unaltered. The
      transthoracic Hemopump device combined with an intraaortic balloon pump is an
      ideal support system for the ischemic, failing heart.

PMID- 9270644
TI  - Left ventricular diastolic function after coronary artery bypass grafting: a
      correlative study with three different myocardial protection techniques.
AB  - BACKGROUND: This study was designed to examine the effect of myocardial
      protection on diastolic function after cardiac operations. METHODS: Subjects were
      patients with normal preoperative diastolic function who were scheduled for
      coronary artery bypass grafting. Group I received anterograde cardioplegia; group
      II received anterograde and retrograde cardioplegia; and group III was protected
      with ventricular fibrillation and intermittent aortic crossclamping. Operations
      were performed with mild hypothermia and ventricular venting through the left
      superior pulmonary vein in all cases. Left ventricular diastolic function was
      evaluated with pulsed-wave Doppler transesophageal echocardiography (samples at
      the mitral valve leaflet: four-chamber view) and left superior pulmonary vein
      flow velocity. The flow patterns were stored on videotape and sent to an
      independent investigator for analysis. Left ventricular ejection fraction was
      calculated with transesophageal echocardiography (short-axis view, two
      dimensional and M-mode). RESULTS: Left ventricular diastolic function, as
      measured by the ratio between the peak velocities during early filling and atrial
      contraction and by systolic diastolic superior pulmonary venous flow ratio, was
      significantly impaired in all three groups 5 minutes after discontinuation of
      cardiopulmonary bypass. At 1 hour after operation, these values had returned to
      control levels only in group III. There was an increased incidence of
      supraventricular arrhythmias in group III. There were no significant hemodynamic
      differences among the three groups. CONCLUSIONS: Left ventricular diastolic
      function was severely impaired after cardiopulmonary bypass. The degree of
      impairment depended on the myocardial protection used. The impairment in
      diastolic function was less when ventricular fibrillation and intermittent aortic
      crossclamping were used, and greater when anterograde and retrograde cardioplegia
      were used.

PMID- 9270645
TI  - Effects of minimal-dose aprotinin on coronary artery bypass grafting.
AB  - OBJECTIVE: To evaluate the effects of minimal-dose aprotinin in patients
      undergoing coronary artery bypass grafting, we conducted a prospective randomized
      study. METHODS: A total of 167 patients were randomized to receive no aprotinin
      treatment (control, n = 57), minimal-dose aprotinin (1.0 x 10(6) KIU; n = 55), or
      low-dose aprotinin (2.7 +/- 0.5 x 10(6) KIU; n = 55). Blood loss and transfusion
      requirements, parameters of clotting and fibrinolysis, renal function, and early
      graft patency rates were assessed. RESULTS: Postoperative blood loss and
      transfusion requirements were significantly (p = 0.01) lower in both the minimal
      dose and low-dose groups than in the control group. The increase in D-dimer level
      after cardiopulmonary bypass was significantly (p < 0.05) less marked in the low
      dose group than in the control group. The alpha 2-plasmin inhibitor and
      plasminogen activator inhibitor-1 levels were significantly (p < 0.05) greater in
      the minimal-dose and low-dose groups than in the control group after bypass,
      suggesting the prevention of fibrinolysis by both aprotinin doses. No
      statistically significant differences in postoperative renal function and early
      vein graft patency rates were noted (control group, 93.8%; minimal-dose group,
      95.5%; low-dose group, 92.3%; p = 0.25). CONCLUSIONS: Aprotinin was not
      associated with a significant increase in the prevalence of renal dysfunction or
      early vein graft occlusion. Minimal-dose aprotinin inhibited enhanced
      fibrinolytic activity and reduced blood loss and transfusion requirements after
      bypass equivalently to low-dose aprotinin. The dose of 1 x 10(6) KIU added to the
      pump prime may be acceptably effective in reducing blood loss in patients
      undergoing primary coronary operations.

PMID- 9270647
TI  - Inverted left atrial appendage: an unrecognized cause of left atrial mass.

PMID- 9270646
TI  - Cerebral dysfunction after coronary artery bypass grafting done with mild or
      moderate hypothermia.
AB  - OBJECTIVE: Ninety-nine patients undergoing elective coronary artery bypass
      grafting were enrolled in a prospective, randomized study to evaluate the
      incidence of cerebral dysfunction after "mild" or "moderate" hypothermia during
      cardiopulmonary bypass. METHODS: Patients were evaluated before and after
      operation before hospital discharge and in some cases at follow-up at least 6
      weeks later with a complete neurologic examination (85 patients) and a battery of
      standard neuropsychometric tests (86 patients). RESULTS: Postoperative changes
      detected by neurologic examination consisted of the appearance of new primitive
      reflexes in both groups. No statistically significant differences in incidence
      were found. The neuropsychometric performances of the two groups were
      statistically similar by either event-rate or group-rate analysis. CONCLUSIONS:
      There is no detectable difference in postoperative cerebral dysfunction in
      patients undergoing coronary artery bypass grafting who are supported by
      cardiopulmonary bypass with either mild or moderate hypothermia.

PMID- 9270648
TI  - Giant atherosclerotic aneurysm of the sinoatrial nodal artery.

PMID- 9270649
TI  - Total anomalous systemic venous drainage to the coronary sinus in association
      with hypoplastic left heart disease: more than a mere coincidence.

PMID- 9270650
TI  - Acute graft-versus-host disease after human heart-lung transplantation: a case
      report.

PMID- 9270651
TI  - Rupture of inflow conduits in the TCI-HeartMate system.

PMID- 9270652
TI  - Nodular pulmonary amyloidosis.

PMID- 9270653
TI  - Hepatic blood flow during cardiopulmonary bypass operations: the effect of
      temperature and pulsatility.

PMID- 9270654
TI  - Methemoglobinemia complicating topical anesthesia during bronchoscopic
      procedures.

PMID- 9270655
TI  - Pulmonary thromboendarterectomy for the treatment of pulmonary embolism caused by
      renal cell carcinoma.

PMID- 9270656
TI  - Right heart bypass with an extracardiac conduit for functionally single ventricle
      with anomalous pulmonary venous connection to the right atrium.

PMID- 9270657
TI  - Isolated primary chylopericardium.

PMID- 9270658
TI  - Technique for one-lung ventilation during video-assisted thoracoscopic surgical
      interruption of patent ductus arteriosus in children.

PMID- 9270659
TI  - Tumor dissemination after video-assisted thoracic surgery: what does it mean?

PMID- 9270660
TI  - Effect of milrinone on coronary artery bypass grafts.

PMID- 9270661
TI  - Hyperoxic cardiopulmonary bypass causes reoxygenation injury and lipid
      peroxidation.

PMID- 9270662
TI  - Historical perspectives of the American Association for Thoracic Surgery. Edward
      William Archibald (1872-1945).

PMID- 9270663
TI  - Age-related susceptibility to experimental autoimmune myasthenia gravis:
      immunological and electrophysiological aspects.
AB  - Susceptibility to experimental autoimmune myasthenia gravis (EAMG) was found to
      decrease with aging in both Lewis and Brown Norway (BN) rats. In this study, the
      difference in susceptibility between young and aged Lewis and BN rats was used to
      analyze factors determining the clinical severity of EAMG. The incidence and
      severity of muscular weakness did not correlate with acetylcholine receptor
      (AChR) loss nor with the ability of antibodies to interfere with AChR function.
      Aged rats showed significantly lower anti-rat AChR antibody titers than young
      rats and developed less severe or no clinical signs of disease. In individual
      young or aged rats, however, no significant correlation was found between the
      clinical signs of disease and anti-rat AChR titer. Neuromuscular transmission was
      found to change with aging as measured by single-fiber electromyography (SFEMG).
      In aged BN rats, increased jitter and blockings were found even before EAMG
      induction. Despite this disturbed neuromuscular transmission, these aged BN rats
      were clinically resistant against induction of EAMG. The results of this study
      indicate that the age-related susceptibility to EAMG is influenced by factors
      determined by the immune attack as well as mechanisms at the level of the
      neuromuscular junction.

PMID- 9270664
TI  - Effect of high-dose intravenous immunoglobulin on serum chemistry, hematology,
      and lymphocyte subpopulations: assessments based on controlled treatment trials
      in patients with neurological diseases.
AB  - The effect of intravenous immunoglobulin (IVIG) on various laboratory values was
      measured immediately before and after completion of serial monthly infusions of
      IVIG (2 g/kg) or an equal volume of placebo over 3-12 months, in 46 patients with
      neuromuscular diseases participating in controlled trials. Hematological,
      lymphocyte subpopulation, and chemistry values were analyzed and compared. After
      IVIG, but not placebo, a 34% reduction in lymphocytes was noted in 44/46 patients
      with a selective reduction of the T cells, but not the B or IL2R-positive cells.
      Counts returned to baseline within 30 days. Creatine kinase levels decreased by
      23% and sedimentation rate increased by 275% after IVIG infusion. A
      nondilutional, artifactual, hyponatremia and hypomagnesemia was noted with IVIG
      but not placebo. We conclude that IVIG affects a variety of serum chemistry and
      hematological values either directly or artifactually by interfering with the
      laboratory method used for the assays. Transient lymphopenia is consistently
      seen, and may play a role in the immunomodulating effect of IVIG.

PMID- 9270665
TI  - Magnetic stimulation excites skeletal muscle via motor nerve axons in the cat.
AB  - Surface magnetic stimulation has been applied directly over skeletal muscle
      (triceps surae) in decerebrated cats. Recordings were made of the twitch
      contraction and electromyographic responses in triceps surae, and of the
      centripetal nerve volley in the sciatic nerve or spinal roots. Stimulus/response
      curves were established up to the maximum output of the magnetic stimulator.
      Neuromuscular blockade abolished the twitch contraction and muscle action
      potential leaving the nerve volley unaffected. Raising the stimulator output to
      its maximum increased the size of the nerve volley but failed to produce any
      muscle response. We conclude that magnetic stimulation applied directly to
      skeletal muscle excites via stimulation of motor nerve axons. The maximum output
      of the stimulator was incapable of exciting muscle fibers by direct
      depolarization. Use of magnetic stimulation in the clinical appraisal of muscle
      function should be interpreted in the knowledge that the stimulator elicits
      contraction only indirectly through nerve stimulation.

PMID- 9270666
TI  - Changes in skeletal muscle histology and metabolism in patients undergoing
      exercise deconditioning: effect of propionyl-L-carnitine.
AB  - To define the skeletal muscle abnormalities in patients undergoing exercise
      deconditioning and evaluate the metabolic effect of propionyl-L-carnitine (PLC),
      muscle biopsies were obtained from 28 patients with effort angina and 31 control
      subjects. Coronary artery disease patients received either placebo (n = 12), PLC
      (1.5 g i.v. followed by infusion of 1 mg/kg/min for 30 min, n = 10), or L
      carnitine (1 g i.v. followed by infusion of 0.65 mg/kg/min for 30 min, n = 6) for
      2 days. Exercise deconditioned patients treated with placebo showed normal muscle
      content of total carnitine and glycogen, and decrease in percentage of type 1
      fibers (P < 0.01) and in the activity of citrate synthase (P < 0.05), succinate
      dehydrogenase (P < 0.05), and cytochrome oxidase (P < 0.05), as compared to
      controls. Both PLC and L-carnitine did not modify muscle fiber composition or
      enzyme activities, but significantly increased muscle levels of total carnitine
      by 42% and 31%, respectively (P < 0.05). Moreover, PLC significantly increased
      glycogen muscle content (P < 0.01), while the equimolar dose of L-carnitine did
      not. This effect, probably due to the anaplerotic activity of the propionic group
      of PLC, suggests that this drug may be effective in improving energy metabolism
      of muscles with impaired oxidative capacity.

PMID- 9270667
TI  - GAA trinucleotide repeat expansion in variant Friedreich's ataxia families.
AB  - Phenotypic variants in Friedreich's ataxia include late onset, preservation of
      the lower limbs tendon reflexes, and slow progression. We describe clinical and
      electrophysiological features from three families with Friedreichlike phenotypes.
      Friedreich's ataxia diagnosis was confirmed by finding two allelic expansions of
      the GAA trinucleotide repeat at the X25 gene. In family 1 both patients had a
      late-onset phenotype with preservation of knee and ankle jerks, lack of
      cardiomyopathy, and preserved H reflex. One of them did not have
      electrophysiologic evidence of sensory axonal neuropathy. Patients from family 2
      showed variability in the age of onset, and 2 out of 3 affected children had
      hyperactive lower limbs reflexes with preserved H reflex. Disease progression in
      a patient from family 3 was very slow after onset at the age of 21. The finding
      of two expanded alleles in these families confirms the wide variability of the
      clinical spectrum of Friedreich's ataxia.

PMID- 9270668
TI  - Spheroid body myopathy revisited.
AB  - Having reported spheroid body myopathy from Indiana (IN) inherited in an
      autosomal-dominant fashion several years ago, we now describe additional findings
      from the Oregon branch--briefly recorded earlier--and confirm earlier studies in
      another clinically affected IN member of this kinship demonstrating identical
      spheroid bodies within the myopathic muscle specimens. The spheroid bodies also
      contained increased amounts of desmin, alpha-B crystallin, and ubiquitin within
      muscle fibers. Our studies now have established that spheroid body myopathy is a
      member of the growing family of desminopathic neuromuscular conditions.

PMID- 9270669
TI  - Corticomotor threshold is reduced in early sporadic amyotrophic lateral
      sclerosis.
AB  - The pathogenesis of idiopathic amyotrophic lateral sclerosis (ALS) remains
      unknown, but accumulating evidence suggests a neuroexcitotoxic mechanism may have
      some credence. Glutamate-induced hyperexcitability of cortical or spinal
      motoneurons may be expected to manifest itself as a reduced threshold for
      activation of these structures. We have measured corticomotor threshold to the
      first dorsal interosseous (FDI) muscles of 48 patients with sporadic ALS using
      magnetic brain stimulation and have correlated the findings with physical signs
      of upper and/or lower motor neuron degeneration. We find that if FDI in patients
      with ALS shows no weakness, wasting, or signs of an upper motor neuron lesion,
      mean corticomotor threshold is significantly lower than in 102 healthy control
      FDI muscles (P = 0.02). In contrast, FDI muscles showing signs of lower motor
      neuron degeneration only or mixed upper and lower motor neuron signs are
      associated with a raised corticomotor threshold (P = 0.008, P < 0.001,
      respectively). We conclude that early in ALS, at a time when hand muscle function
      is normal, corticomotor threshold is reduced and suggest that this may be a
      manifestation of abnormal excitability of cortical or spinal motoneurons to
      neurotransmitters, whose action will ultimately lead to cell death.

PMID- 9270670
TI  - Hemolytic anemia associated with intravenous immunoglobulin.
AB  - Intravenous immunoglobulin (IVIg) is a useful tool in the treatment of a variety
      of neuromuscular disorders. Though IVIg therapy is generally safe, hemolytic
      anemia is a potentially serious complication that is often overlooked, and is
      currently not listed in product inserts. We analyzed 45 patients who received
      IVIg therapy, including 38 consecutive patients who received IVIg over a 13-month
      period. On 42 patients, direct antiglobulin testing was performed, searching for
      antibodies to the patients' own blood type. Of these 42 patients, 12 developed
      passive sensitization with antibodies to their own blood group antigens after
      receiving IVIg. Of these 12 patients, 11 patients developed hemolysis severe
      enough to lower the hemoglobin level by at least 1 g/dL. Of these patients, 3
      required blood transfusion, and 1 had IVIg therapy truncated because of the
      hemolysis. Antibodies to blood group antigens are found in all commercial
      preparations of IVIg. Though most patients do not have clinically significant
      hemolysis, clinicians should be aware of this potentially serious complication.
      Careful monitoring of hemoglobin levels during IVIg therapy is recommended.

PMID- 9270671
TI  - Low-dose guanidine and pyridostigmine: relatively safe and effective long-term
      symptomatic therapy in Lambert-Eaton myasthenic syndrome.
AB  - Guanidine hydrochloride is known to be highly effective in the symptomatic
      treatment of the Lambert-Eaton myasthenic syndrome (LEMS). However, because of
      its potentially dangerous side reactions of hematologic abnormalities and renal
      insufficiency, 3,4-diaminopyridine, which is not readily available in the United
      States, is recommended as the preferred drug for LEMS. We used low-dose guanidine
      and pyridostigmine combination therapy in 9 patients with LEMS and analyzed its
      long-term safety and effectiveness. In all patients, a liberal amount of
      pyridostigmine was used, while daily guanidine dose was kept below 1000 mg a day,
      and guanidine was given between pyridostigmine dosings. This combination therapy
      was used for 3-102 months (mean: 34.1 months) and improved clinical status in all
      patients. Although guanidine had to be discontinued due to severe
      gastrointestinal symptoms in 3 cases, no serious side reactions such as bone
      marrow suppressions or signs of renal insufficiency developed in any case. Thus,
      we conclude that low-dose guanidine therapy is relatively safe and effective for
      long-term symptomatic treatment of LEMS when it is combined with pyridostigmine.

PMID- 9270672
TI  - Clinical features of perineuritis.
AB  - We report 13 patients with pathologically confirmed perineuritis. Seven patients
      had diabetes mellitus, 5 had nutritional abnormalities, 2 had associated
      rheumatological illnesses, 2 had sepsis with multiorgan failure, and 1 had a
      history of malignancy. Electrophysiologic testing demonstrated mononeuritis
      multiplex in 7, demyelinating neuropathy in 4, distal sensory and motor
      neuropathy in 1, and polyradiculoneuropathy in 1. Twelve patients received
      immunomodulating therapy with variable responses. We conclude that perineuritis
      is associated with a number of different systemic conditions and several clinical
      patterns of peripheral neuropathy. Response to immunomodulation is variable. The
      most frequent association is with diabetes mellitus, a previously unrecognized
      association.

PMID- 9270673
TI  - Changes in corticomotor excitation and inhibition during prolonged submaximal
      muscle contractions.
AB  - Changes in motor evoked potential (MEP) amplitude, post-MEP silent period
      duration, and interpolated twitch torque were measured using transcranial
      magnetic (TMS) and electrical (TES) stimulation during a 20% maximum voluntary
      contraction of the elbow flexors sustained to exhaustion. TMS- and TES-induced
      MEP amplitude increased progressively over the contraction period up until the
      point of exhaustion. The TMS-induced silent period was prolonged only during the
      second half of the contraction period, the time course being different from that
      of the MEP responses, whereas the TES-induced silent period did not change. The
      findings indicate that corticomotor excitability increases during a sustained
      submaximal voluntary contraction and that, as fatigue develops, there is a
      progressive buildup of intracortical inhibition. This may represent a mechanism
      whereby corticomotor output is maintained at an appropriate level to preserve
      optimal motor unit firing frequencies during a fatiguing contraction.

PMID- 9270674
TI  - Electromyography of the external anal sphincter in patients with Parkinson's
      disease and multiple system atrophy: frequency of abnormal spontaneous activity
      and polyphasic motor unit potentials.
AB  - Electromyographic studies of the external anal sphincter muscle have received
      increasing attention in the differential diagnosis of patients with parkinsonism.
      Based on the fact that the external anal sphincter muscle is partly innervated by
      fibers that originate in Onuf's nucleus in the segments S2-S4 of the spinal cord,
      an increased duration of the motor unit potentials (MUPs) and an increased
      polyphasia may reflect neuronal loss of these lower motor neurons characteristic
      for multiple system atrophy. We report the results of anal sphincter
      electromyography in 15 patients with clinically probable multiple system atrophy
      (MSA) and 10 patients with Parkinson's disease (PD). There was no significant
      difference between patients with MSA and patients with PD concerning the duration
      of MUPs, mean number of phases, and rate of polyphasic motor potentials. There
      was a tendency for a longer mean duration and increased polyphasia in patients
      with MSA compared to patients with PD. Spontaneous activity was recorded in 11 of
      15 patients with MSA occurring especially in patients with MSA of the
      striatonigral type, but not in patients with PD. In this study, the duration of
      MUPs and the rate of polyphasia were unreliable criteria in the
      electrophysiological differential diagnosis of patients with parkinsonism.
      Abnormal spontaneous activity, although difficult to detect, is a more specific
      marker for neuronal degeneration of Onuf's nucleus occurring in patients with
      MSA.

PMID- 9270676
TI  - Terminal latency index in the carpal tunnel syndrome.
AB  - Our retrospective study assessed the validity of the median motor terminal
      latency index (m-TLI) in evaluation of carpal tunnel syndrome (CTS). In patients
      deemed most likely to have CTS, the mean m-TLI was markedly reduced at 0.25 while
      the controls had a mean m-TLI of 0.44. The m-TLI was abnormal in all of the
      "probable CTS" hands and in none of the control hands. The m-TLI is a sensitive
      adjunctive electrophysiologic measure for the presence of CTS.

PMID- 9270677
TI  - Amyotrophic lateral sclerosis in Mexico: validation of two predictive scales.

PMID- 9270675
TI  - Collet-Sicard syndrome mimicking neuralgic amyotrophy.
AB  - A man with shoulder pain, wasting, and weakness had ipsilateral cranial nerve
      abnormalities. Electrodiagnostic studies supported a diagnosis of neuralgic
      amyotrophy, but we later demonstrated a spinal accessory mononeuropathy with
      ipsilateral hypoglossal weakness (Collet-Sicard syndrome). Magnetic resonance
      imaging demonstrated an inaccessible occipital condyle mass, and disseminated
      adenocarcinoma was subsequently diagnosed. Although cranial mononeuropathies can
      occur in neuralgic amyotrophy, this case illustrates the importance of
      identifying a focal lesion, and highlights the localizing value of
      electrodiagnosis.

PMID- 9270678
TI  - Recurrent polyradiculoneuropathy with the 17p11.2 deletion.
AB  - Hereditary neuropathy with liability to pressure palsies (HNPP) classically
      occurs as recurrent focal neuropathy. We report the first known instance of HNPP
      manifesting, over a 15-year period, as a recurrent sensorimotor polyneuropathy
      and confirmed by the presence of the PMP-22 gene deletion. We suggest that the
      molecular study of the 17p11.2 region could be an effective non invasive
      investigative tool in cases of chronic recurrent polyneuropathy associated with
      episodes of nerve palsy.

PMID- 9270679
TI  - Influence of stimulus cross talk on results of the twitch-interpolation technique
      at the biceps brachii muscle.
AB  - Biceps brachii muscles of five healthy volunteers were tested with a high
      resolution twitch-interpolation technique. Parameters of the electrical surface
      stimulation were varied. It was found that a supramaximal stimulus strength
      activates both biceps and triceps brachii motor units simultaneously severely
      affecting twitch-interpolation results. Crosstalk contamination of twitches,
      however, can be avoided, if submaximal stimuli are used yielding twitch
      interpolation results for the biceps-brachii that are similar to those of the
      quadriceps muscle.

PMID- 9270681
TI  - Autosomal dominant centronuclear myopathy: report of a new family with clinical
      features simulating facioscapulohumeral syndrome.
AB  - The centronuclear myopathies are a clinically and genetically heterogeneous group
      of disorders which share similar histological features on muscle biopsy. The
      familial cases have been classified genetically as X-linked or autosomal in
      inheritance. The autosomal forms usually have a later onset and milder course as
      compared to the X-linked form. Thirteen families with autosomal dominant
      centronuclear myopathy have been previously described. We describe an additional
      family with unique clinical features which initially suggested a
      facioscapulohumeral syndrome.

PMID- 9270680
TI  - Electromyographic and lower extremity short time to inversion recovery magnetic
      resonance imaging findings in lumbar radiculopathy.
AB  - To determine if short TI (time to inversion) recovery (STIR) magnetic resonance
      imaging (MRI) is useful in assessing lower extremity (LE) denervation in subacute
      lumbar radiculopathy (LR), 25 subjects underwent lumbar spine MRI, LE STIR MRI
      and needle electromyography (EMG). In 23 (92%) subjects there was a positive
      correlation between LE STIR MRI and EMG (P < 0.009). Increased signal intensity
      on LE STIR MRI corresponds closely with spontaneous activity on EMG in subacute
      LR and may be a useful adjunct diagnostic tool.

PMID- 9270682
TI  - Correlation between muscle metabolism and changes in M-wave and surface
      electromyogram: dynamic constant load leg exercise in untrained subjects.
AB  - In untrained subjects exercising on a cycle at constant work loads presented at a
      sub- or suprathreshold level, reduced M wave amplitude with lengthening of
      duration was measured in vastus lateralis muscle during and after suprathreshold
      exercise. M wave changes were correlated with increased blood lactate
      concentration. At the two work load levels, the increase in root mean square of
      EMG was rapidly closely adjusted to that of oxygen consumption, confirming the
      reality of adaptative reflex mechanisms in leg muscles during cycling.

PMID- 9270683
TI  - Technology review: nervepace digital electroneurometer.

PMID- 9270684
TI  - Should every unclear neuromuscular symptom be termed "paraneoplastic"?

PMID- 9270685
TI  - Recurrent focal myositis.

PMID- 9270686
TI  - Combined low-rate nerve stimulation and maximal voluntary contraction in the
      detection of compound muscle action potential facilitation in Lambert-Eaton
      myasthenic syndrome.

PMID- 9270687
TI  - Case-control studies in multiple sclerosis.

PMID- 9270688
TI  - Historical cohort studies in multiple sclerosis.

PMID- 9270689
TI  - Ecologic studies of multiple sclerosis.

PMID- 9270690
TI  - Cluster studies in multiple sclerosis.

PMID- 9270691
TI  - A multicenter study methodologic experience from a multicenter case-control study
      in Italy. The Italian Multiple Sclerosis Study Group.

PMID- 9270692
TI  - Selected reviews common childhood and adolescent infections and multiple
      sclerosis.

PMID- 9270693
TI  - Diet and multiple sclerosis.

PMID- 9270694
TI  - Canine distemper virus and multiple sclerosis.

PMID- 9270695
TI  - Exposure to organic solvents and multiple sclerosis.

PMID- 9270696
TI  - Data collection guidelines for questionnaires to be used in case-control studies
      of multiple sclerosis.

PMID- 9270697
TI  - Physician organizations.

PMID- 9270698
TI  - Controversy over physician-assisted suicide.

PMID- 9270699
TI  - Controversy over physician-assisted suicide.

PMID- 9270700
TI  - Computerizing patient education documents. Here's a way to clean out those files!

PMID- 9270701
TI  - Insect repellents. What really works?
AB  - DEET remains one of the most effective repellents against a wide variety of
      insects. Although adverse reactions have been reported in the medical literature
      and magnified in the press, the compound is remarkably safe and has been used by
      hundreds of millions of people over the past 40 years. Permethrin is a better
      deterrent of ticks and, like DEET, is remarkably safe. Concomitant use of these
      two agents provides superior protection. Citronella and a bath oil, Avon Skin-So
      Soft, also provide limited protection against some types of flying insects. The
      promise of new agents or protective strategies is on the horizon. Recently it was
      shown that retroviral vectors could be used to integrate and express foreign
      genes in the malaria mosquito, Anopheles gambiae. Conceivably, a genetically
      engineered mosquito that is resistant to malaria and other transmissible diseases
      may one day be developed, obviating some of the need for repellents. Almost
      certainly, future research will yield additional agents to further protect
      against mosquitoes.

PMID- 9270702
TI  - Cholesterol management in patients with heart disease. Emphasizing secondary
      prevention to increase longevity.
AB  - Advances in treatment of elevated cholesterol levels and recent documentation of
      efficacy and safety in clinical trials justify expanded use of cholesterol
      lowering therapy in clinical practice. Patients with CHD or other forms of
      clinical atherosclerotic disease can benefit from aggressive cholesterol
      management. Maximal dietary modification, weight control, and physical activity
      are valuable adjuncts to drug therapy in secondary prevention. Recent studies
      have shown that appropriate use of cholesterol-lowering drugs is cost-effective
      and efficacious in patients with CHD. Use of such drugs can increase patients'
      life expectancy. Primary care physicians have a key role in instituting intensive
      cholesterol management in patients with clinically manifest atherosclerotic
      disease. Furthermore, they should take the lead in coordinating with
      cardiovascular specialists to manage cholesterol levels in patients who have had
      a recent acute coronary syndrome or undergone a revascularization procedure.

PMID- 9270703
TI  - Dispelling myths about acne.
AB  - Virtually no one escapes adolescence and early adulthood unscathed by acne.
      However, advanced methods of therapy are now available to deal with all but the
      most recalcitrant forms of the condition. Unfortunately, stereotypical notions
      about causes and treatments still persist, and as Dr Landow points out, patient
      education to dispell these myths is an important part of management.

PMID- 9270704
TI  - Topical treatments for photoaged skin. Separating the reality from the hype.
AB  - Most patients have committed the usual folly of recreational sunbathing in
      childhood, and in adulthood they notice the manifestations in the mirror.
      Increasingly, they are seeking professional advice regarding the growing stream
      of products that promise to improve their photoaged skin. Physicians need to be
      informed about the great range and complexity of products available, if for no
      other reason than to steer patients clear of traveling-medicine-show products. A
      better reason is to be able to provide guidance on proper use of formulations
      that have proven benefit.

PMID- 9270705
TI  - Androgenetic alopecia. Battling a losing proposition.
AB  - Some degree of hair loss with aging is inevitable in both men and women. The
      exact underlying mechanism is not well understood. Although genetic factors have
      a role in the development of androgenetic alopecia, the outcome in an individual
      patient cannot be reliably predicted on the basis of family history. Balding
      tends to begin earlier in men and to develop in well-recognized patterns. Women
      have more diffuse hair loss that often occurs after menopause. The available
      treatment options, such as topical minoxidil therapy, hair transplantation, and
      other surgical techniques, are not very successful. Lessening patients' anxiety
      about hair loss by reassuring them that they will not go totally bald immediately
      may be the most effective management.

PMID- 9270706
TI  - Basal and squamous cell carcinomas. What every primary care physician should
      know.
AB  - Skin cancer screening should be a part of every routine physical examination, and
      suspicious lesions should be biopsied. Basal and squamous cell carcinomas are
      highly curable with early diagnosis and treatment. Patient education about
      protection from the sun is an important part of treatment. Patients with a
      history of basal or squamous cell carcinoma are at increased risk for new skin
      cancers as well as recurrences, and lifelong, regular, total cutaneous
      examinations are essential to detect potentially curable skin carcinomas and
      melanomas. The frequency of follow-up depends on the number and types of previous
      skin cancers, as well as other risk factors, but as a rule, examinations should
      be performed at least yearly. Such a surveillance strategy should decrease
      morbidity and mortality among patients with these dangerous neoplasms.

PMID- 9270707
TI  - Fibromyalgia, chronic fatigue, and other iatrogenic diagnostic algorithms. Do
      some labels escalate illness in vulnerable patients?
AB  - Contemporary medicine has the sophistication to identify the clinical settings in
      which the hunt for a diagnosis can be harmful to a patient's health. Which
      patients are best served by a prolonged search for a cause? Why has the disease
      illness paradigm backfired for so many patients? Dr Hadler challenges readers to
      look at the difficult questions linked with diagnostic labels that might teach
      patients to stay sick.

PMID- 9270708
TI  - Psittacosis. Is contact with birds causing your patient's pneumonia?
AB  - Psittacosis is an uncommon source of community-acquired pneumonia but can cause
      significant morbidity and possibly death if not properly diagnosed and treated.
      Although it occurs most often among handlers of pet psittacine birds, it can be
      contracted during poultry processing and other contacts with nonpsittacine birds.
      Clinical presentation is nonspecific, and history taking is often critical in
      establishing the diagnosis. All suspected cases should be confirmed with
      serologic antibody testing. Whenever possible, the source of the infection should
      be identified to prevent further spread of the illness. Infections in humans
      should be reported to the CDC.

PMID- 9270709
TI  - A closer look at vitamin E. Can this antioxidant prevent chronic diseases?
AB  - Vitamin E, the most effective natural free radical scavenger identified to date,
      is taking America by storm-and apparently for good reason. Reports of benefits
      ranging from Improved Immunity to prevention of cancer and cardiovascular disease
      are appearing regularly. In this article, the authors review the scientific
      literature to help you evaluate whether patients might benefit from supplemental
      vitamin E.

PMID- 9270710
TI  - Coronary heart disease. From early defeats to current victories, the battle
      continues.

PMID- 9270711
TI  - How to spot depressed patients in your practice.
AB  - This is the third in a series of short articles on management of common problems
      primary care physicians encounter in the office setting. Written by members of
      Postgraduate Medicine's Editorial Council, these articles offer a personal
      perspective gleaned from hands-on experience. Here, Dr Matthies presents his
      approach to management of depression-how to recognize clues to the disorder, how
      to confront patients with the diagnosis, and where to go from there.

PMID- 9270712
TI  - Aspiration pneumonia. Strategies for early recognition and prevention.
AB  - Aspiration is the result of dysfunction during the oral, pharyngeal, or
      esophageal stage of deglutition. Depending on the type of aspirate, the resultant
      lung injury may include chemical or bacterial inflammation or obstruction of the
      airways. Tools for evaluation include roentgenography, upper GI tract studies,
      bronchoscopy, and esophageal pH studies. Medical management is primarily
      supportive. Because aspiration pneumonia has a high morbidity rate, prevention
      involving early recognition and modification of predisposing factors whenever
      possible is critical for improving outcomes.

PMID- 9270713
TI  - Common urologic disorders. When to treat and when to refer.
AB  - Healthcare will continue to see a trend toward fewer referrals to specialists.
      Consequently, primary care physicians must understand the evaluation and
      management of the most common urologic disorders. This understanding, coupled
      with the knowledge of when to refer to a urologist, will enable safe management.

PMID- 9270714
TI  - Acute sinusitis in adults. Difficult to diagnose, essential to treat.
AB  - Acute sinusitis is difficult to diagnose. Diagnosis depends on obtaining a
      complete history and physical examination in addition to use of radiographic
      diagnostic aids and, if necessary, sinus aspiration. Once the diagnosis is made,
      empirical treatment with antibiotic agents and adjunctive measures should be
      started. Because most acute sinus infections are caused by H influenzae and S
      pneumoniae, the preferred antibiotic for treatment is amoxicillin or TMP-SMZ.
      Timely and appropriate therapy prevents complications. Symptoms persisting after
      completion of an appropriate course of treatment are an indication for referral
      to an otolaryngologist.

PMID- 9270715
TI  - Newer findings on a unified perspective of copper restriction and cardiomyopathy.
AB  - The cuproenzymes lysyl oxidase, cytochrome-c oxidase, and superoxide dismutase
      are key factors in understanding the cardiac hypertrophy and cardiomyopathy
      associated with dietary copper restriction. The role of copper in cardiac lipid
      and energy metabolism as a consequence of changes in some of these enzyme
      activities in comparison with what is known about normal cardiac substrate
      utilization is discussed here. While the decrease in the nuclear encoded subunits
      of cytochrome-c oxidase in hearts from copper-deficient rats is known, new
      evidence suggests that other factors, such as ATP synthase metabolism may be
      exerting an influence upon this observation. While this review focuses on newer
      knowledge about energy and fatty acid metabolism in copper deficiency, the
      extracellular matrix is considered as well. This complex interplay of
      extracellular and cellular events in copper restriction is outlined as a model
      for further studies of this unique model of concentric hypertrophy.

PMID- 9270717
TI  - alpha-fetoprotein as a biologic response modifier: relevance to domain and
      subdomain structure.
AB  - In the present review, the structure of alpha-fetoprotein (AFP) is discussed in
      consideration of AFP membership and position in the albuminoid supergene family
      in relation to other gene family members. Ontogenetic AFP gene expression is then
      discussed in view of AFP mRNA presence in various tissues at different times
      during development. The multiple molecular forms of AFP is also presented in
      relation to published reports of AFP binding proteins and cell surface receptors.
      The review proceeds on to present AFP as a potential model of a modular/cassette
      protein based on sequence comparison with cleaved fragments of prohormones and
      biological response modifiers. Such cleaved fragments could potentially serve as
      peptide messengers for vascular, neuroendocrine, and digestive biological
      activities. Following a discussion on fibrin binding and serine proteases, AFP
      cytoskeletal, extracellular matrix, and cellular adhesion interactions are
      considered. AFP as a carrier/transport protein based on structural relationships
      is further elucidated by examination of the various ligands bound to AFP and its
      hormone interaction. Since AFP binds heavy metals, the question is posed of
      whether AFP could function as an antioxidant. An analysis of transcription
      factors, tumor suppressors, and homeodomain proteins follows, which is interfaced
      with the concept of programmed cell death in light of amino acid sequence matches
      detected on the AFP molecule. Emphasis was naturally placed upon the homeodomain
      protein sequence stretches since AFP is a fetal, phase-specific protein found
      throughout embryogenesis, histogenesis, and organogenesis. In keeping with
      histogenesis, a discussion of AFP and eye lens protein development is presented.
      Finally, AFP sequence analysis presented in light of members of the
      immunoglobulin superfamily, autoimmune disorders, and various disease states
      culminates the review. A closing discussion then summarizes regions of
      presumptive matched protein identities on each of AFP's three domains.

PMID- 9270716
TI  - Glucose-6-phosphatase structure, regulation, and function: an update.
AB  - Work on the glucose-6-phosphatase system has intensified and diversified
      extensively in the past 3 years. The gene for the catalytic unit of the liver
      enzyme has been cloned from three species, and regulation at the level of gene
      expression is being studied in several laboratories worldwide. More than 20 sites
      of mutation in the catalytic unit protein have been demonstrated to underlie
      glycogenesis type 1a. inhibition of glucose-6-P hydrolysis by several newly
      identified competitive and time-dependent, irreversible inhibitors has been
      demonstrated and in several instances the predicted effects on liver glycogen
      formation and/or breakdown and on blood glucose production have been shown.
      Refinements in and additions to the presently dominant "substrate transport
      catalytic unit" topological model for the glucose-6-phosphatase system have been
      made. A new model alternative to this, based on the "combined conformational
      flexibility-substrate transport" concept, has emerged. Experimental evidence for
      the phosphorylation of glucose in liver by high-K(m),glucose enzyme(s) in
      addition to glucokinase has continued to emerge, and new in vitro evidence
      supportive of biosynthetic functions of the glucose-6-phosphatase system in this
      role has appeared. High levels of multifunctional glucose-6-phosphatase have been
      shown present in pancreatic islet beta cells. Glucose-6-P has been established as
      the likely insulin secretagog in beta cells. Interesting differences in the
      temporal responses of glucose-6-phosphatase in kidney and liver have been
      demonstrated. An initial attempt is made here to meld the hepatic and pancreatic
      islet beta-cell glucose-6-phosphatase systems, and to a lesser extent the kidney
      tubular and small intestinal mucosal glucose-6-phosphatase systems into an
      integrated, coordinated mechanism involved in whole-body glucose homeostasis in
      health and disease.

PMID- 9270718
TI  - Procedures for embalming cadavers for the dissecting laboratory.

PMID- 9270719
TI  - Characteristics of the prolactin stimulation of iodide uptake into mouse mammary
      gland explants.
AB  - We have recently reported that prolactin (PRL) stimulates iodide uptake into
      cultured mouse mammary tissues. This effect occurs in both TCA soluble and
      insoluble tissue fractions. The effect of PRL apparently involves an RNA-DNA
      dependent mechanism, since actinomycin D and cyclohexamide abolish the PRL
      stimulation of iodide uptake and its incorporation into protein. Perchlorate and
      thiocyanate, inhibitors of the iodide transporter, also abolish the PRL effects
      on iodide uptake and incorporation. Similarly, propylthiouracil and
      aminotriazole, inhibitors of peroxidase, abolish both effects of PRL. Finally,
      the extent of iodide uptake in mammary cells is suppressed by about 50% in sodium
      free medium. These studies thus suggest the existence of a sodium-iodide
      symporter in the mammary gland which has characteristics similar to the iodide
      transporter in the thyroid gland-that is, it is sodium dependent and is inhibited
      by perchlorate and thiocyanate. The fact that both iodide transporter inhibitors
      and peroxidase inhibitors abolish PRL-stimulated iodide uptake and incorporation
      suggests that there may be a coupled mechanism involving the iodide transporter
      and the peroxidase enzyme.

PMID- 9270720
TI  - Nutritional regulation of plasma tumor necrosis factor-alpha and plasma and
      urinary nitrite/nitrate responses to endotoxin in cattle.
AB  - Effects of dietary protein level with and without L-arginine (Arg) infusion on
      plasma tumor necrosis factor-alpha (TNF-alpha) response to endotoxin
      (lipopolysaccharide [LPS]) as well as plasma concentration and urine output of
      nitrite and nitrate (NOx), the stable end products of nitric oxide radical (NO),
      were studied in beef heifers (275-310 kg body wt). The animals were fed low- (LP;
      7.96%) or high- (HP; 13.94%) protein diets for 10 days before LPS administration
      (Escherichia coli; 0.2 microgram/kg, iv). L-Arginine in saline (0.5 g/kg body wt)
      or saline was infused for 8 hr with one-third of total Arg infused before LPS
      administration. Plasma TNF-alpha concentrations increased in all heifers after
      LPS injection (peak at 1 hr and return to baseline at 4 hr); however,
      concentrations were lower in HP- than in LP-fed heifers at 1, 2, and 3 hr.
      Infusion of Arg did not affect plasma TNF-alpha response to LPS. Plasma NOx
      concentrations increased in all heifers after LPS challenge; compared with
      saline, Arg infusion increased the total response (integrated area under
      concentration curve) in LP- but not in HP-fed heifers. Relative to pretreatment
      period, the rate of NOx output in urine collected 2-6 hr after LPS administration
      increased in all heifers regardless of dietary protein level and was further
      amplified by Arg infusion. The rate of NOx output in urine collected 6-24 hr
      after LPS challenge was even higher in LP-fed heifers infused with Arg but
      returned to the basal values in other groups. Activity of hepatic inducible NO
      synthase was not affected by LPS, Arg, or dietary protein level at the time
      points studied. The data suggest that dietary protein levels can modulate both
      TNF-alpha and NO responses to LPS in cattle; high dietary protein intake
      decreases TNF-alpha response and attenuates the conversion of supplemental Arg to
      NO.

PMID- 9270721
TI  - Atria and ventricles of copper-deficient rats exhibit similar hypertrophy and
      similar altered biochemical characteristics.
AB  - Male Holtzman rats were offered a semipurified low-copper (Cu) diet (0.36 mg
      Cu/kg) for 5-6 weeks to further characterize cardiac hypertrophy, which
      accompanies Cu deficiency. Cu-adequate (controls) were given supplemental Cu (20
      micrograms/ml) in their drinking water, and Cu-deficient rats were given
      deionized water. Cu-deficient rats had lower plasma ceruloplasmin activity, lower
      hemoglobin levels, higher heart weights, and similar body weights compared with
      Cu-adequate rats. The relative degree of hypertrophy in the right ventricle of Cu
      deficient rats was significantly higher (2.3-fold) than that in the left
      ventricle and atria (both were 1.9-fold higher than the values in Cu-adequate
      rats). Edema was not detected. Ventricles and atria of Cu-deficient rats had
      markedly lower Cu and no significant differences in iron concentrations compared
      with Cu-adequate rats. Heart protein concentrations were not altered consistently
      by Cu deficiency. Enzyme activities of the cuproenzymes cytochrome-c oxidase
      (CCO), copper, zinc-superoxide dismutase (SOD), dopamine beta-monooxygenase
      (DBM), peptidylglycine alpha-amidating monooxygenase (PAM), and the selenoenzyme
      glutathione peroxidase (GPX) were measured in the atria and ventricles. Cu
      deficiency resulted in lower specific activities of all cuproenzymes, with the
      exception of ventricular PAM. GPX was not altered by chamber region or diet.
      Specific activity of PAM was 200-fold higher in atria than in ventricles in
      control rats. Catecholamine analyses by HPLC confirmed that, like ventricular
      tissue, atria of Cu-deficient rats had lower noreplnephrine and higher dopamine
      concentrations, consistent with lower DBM activity. Another experiment detected
      no differences between the two dietary groups in mean arterial blood pressure,
      heart rates, or responses after challenge with anglotensin II, phenylepherine, or
      acetylocholine in cannulated rats. In this Cu-deficient rat model, all chambers
      of the heart exhibit similar and marked hypertrophy. Biochemical alterations
      following dietary Cu deficiency were also similar in atria and ventricles. The
      hypertrophic response appears different from the response to simple pressure or
      volume overload.

PMID- 9270722
TI  - Direct action of melatonin on hen ovarian granulosa cells to lower responsiveness
      to luteinizing hormone.
AB  - The presence of a melatonin-binding component in the membrane fraction of the
      ovarian granulosa cells of hens that has characteristics of a receptor such as
      high affinity, limited capacity, reversible binding, and binding specificity was
      demonstrated by radioligand binding assays. When the cells were incubated in
      vitro with various concentrations of luteinizing hormone (LH) in the presence and
      absence of melatonin (1 and 5 nM), the dose-response curve for the LH-stimulated
      progesterone production was shifted to a higher concentration of LH: ED50 of LH
      was approximately two times greater in the presence of melatonin. The results
      suggest a direct action of melatonin on the ovarian granulosa cells of the hen to
      lower the responsiveness to LH for progesterone production.

PMID- 9270723
TI  - Effects of epidermal growth factor (EGF) and prolactin on EGF receptor
      cytoskeletal association in mammary epithelial cells.
AB  - Prolactin treatment of NMuMG mammary epithelial cells inhibits the ability of
      epidermal growth factor (EGF) to transduce a variety of signals, possibly by
      interfering with receptor tyrosine phosphorylation. However, the mechanism by
      which prolactin inhibits EGF receptor signaling is unclear. The objective of this
      study was to evaluate the effects of prolactin on the dynamics of EGF receptor
      degradation and resynthesis, and on the association of the receptor with the
      cytoskeleton. EGF decreased the EGF receptor content of NMuMG cells, and this
      decrease was unaffected by prolactin treatment. Subsequent to the decrease in EGF
      receptors, cells reaccumulated EGF receptors, and this re-accumulation was also
      unaffected by prolactin. In other studies, EGF induced a rapid association of EGF
      receptor with Triton X-100-insoluble (cytoskeletal) elements. The cytoskeletally
      associated receptors were more heavily tyrosine phosphorylated than soluble
      receptors in the absence of prolactin. In the presence of prolactin, similar
      amounts of EGF receptor associated with the cytoskeleton, but both cytoskeletal
      and soluble receptors exhibited decreased tyrosine phosphorylation. These studies
      indicate that the effects of prolactin on EGF receptor signaling are not likely
      to be due to altered receptor dynamics or cytoskeletal association but are more
      likely due to an alteration in receptor kinase activity.

PMID- 9270724
TI  - Long-term exposure of HL60 cells to 1,25-dihydroxyvitamin D3 reduces their
      tumorigenicity: a model for cancer chemoprevention.
AB  - Several lines of evidence suggest that 1,25-dihydroxyvitamin D3 (1,25D3) may be
      important in chemoprevention of human cancer. Here, we show that human
      promyelocytic leukemia cells HL60 cultured in the presence of 30 nM 1,25D3 (30A
      cells) for 3 years exhibited a reduced rate of tumor growth when injected into
      nu/nu mice, while cells grown in 40 nM 1,25D3 (40AF cells) failed to form
      detectable tumors in 11 out of the 12 inoculated mice, interestingly, both 30A
      and 40AF cells grew approximately twice as fast as the parental HL60-G cells
      under tissue culture conditions, even in the presence of 1,25D3, to which they
      developed resistance. Tests of the susceptibility of these cells to natural
      killer (NK) cell cytotoxicity showed that 40AF, but not HL60-G or 30A cells, were
      targets for the murine spleen NK cells. However, lysis of 30A cells was also
      detected when human NK cells were used in this assay, though the effector-to
      target cell ratio necessary to obtain significant lysis above background levels
      was higher for 30A (80:1) than for 40AF (10:1) cells. These results suggest a
      mechanism for the reported chemopreventive effects of sunlight-generated 1,25D3
      or dietary vitamin D3.

PMID- 9270725
TI  - Changes in inducible nitric oxide synthase expression in experimental
      glomerulonephritis.
AB  - We assessed changes in transcriptional activation of the inducible isoform of
      nitric oxide synthase (iNOS) in a model of macrophage-dependent proliferative
      glomerulonephritis in the rat resembling human forms of rapidly progressive
      nephritis. By the use of a cDNA probe derived from rat glomerular RNA and an
      RNase protection assay, iNOS expression was assessed at early and late stages of
      the disease and was correlated with the extent of macrophage infiltration.
      Prominent iNOS expression occurred in isolated glomeruli 24 hr after onset of
      immune injury when marked glomerular infiltration by macrophages also occurred.
      Treatment of animals with immune injury with the arachidonic acid cyclooxygenase
      inhibitor, indomethacin, potentiated iNOS expression. iNOS expression was short
      lived; it was markedly reduced on Day 2 of injury and undetectable on Days 4 and
      10, despite sustained infiltration of glomeruli by macrophages. These
      observations suggest that in glomerular immune injury the enhanced expression of
      iNOS is not sustainable possibly due to downregulatory factors generated in the
      course of injury.

PMID- 9270726
TI  - Insulin-like growth factor-I stimulates proliferation of mouse uterine epithelial
      cells in primary culture.
AB  - Estrogens stimulate proliferation and differentiation of uterine epithelial cells
      in vivo. Mitogenic action of estrogens may be mediated by growth factors such as
      insulin-like growth factor-I (IGF-I). This study was designed to determine
      whether IGF-I and insulin affect proliferation of uterine epithelial cells
      obtained from 3- to 4-week-old immature female mice in a serum-free culture
      system. The epithelial cell number on Day 5 in culture was significantly
      increased by adding IGF-I (10 and 100 ng/ml) or insulin (100 and 1000 ng/ml) to
      the culture media, indicating that IGF-I is more effective than insulin in
      inducing the epithelial growth. The epithelial DNA synthesis was significantly
      stimulated by IGF-I (1 and 10 ng/ml), suggesting that both the epithelial
      proliferation and their detachment from substratum are stimulated by 1 ng/ml of
      IGF-I, but that the former is more accelerated than the latter by 10 ng/ml of IGF
      I. These results demonstrate that both IGF-I and insulin directly stimulate the
      growth of uterine epithelial cells, and suggest that insulin may act via IGF-I
      receptors. IGF-I immunoreactivity was detected in the cytoplasm of the cultured
      cells, indicating that the cells synthesize IGF-I. Estradiol-17 beta (E2) at
      lower concentrations (0.001-0.1 nM) tended to increase the number of epithelial
      cells, while E2 at higher concentrations (1 to 100 nM) did not affect it. It is
      highly probable that IGF-I produced in endometrial cells induces their
      proliferation by an autocrine or paracrine mechanism.

PMID- 9270727
TI  - Geophagy: a vestige of palaeonutrition?

PMID- 9270728
TI  - Laboratory diagnosis of acute measles infections in hospitalized children in
      Zambia.
AB  - Laboratory diagnosis of measles infection is rarely performed in developing
      countries and tends to depend on clinical symptoms alone. We evaluated detection
      of immunoglobulin M (IgM) antibodies for confirmation of acute measles infection
      in Zambia. In 149 hospitalized children with clinical diagnosis of measles, IgM
      antibodies were detected in 88.6% (132/149). The IgM-positive rate increased with
      time after onset of skin rash and all samples were positive after 4 days. In
      addition to IgM antibody test, virus isolations from throat swabs using B95a
      cells were also performed. These were positive in only 20.9% (14/67), and both
      IgM and virus isolation in combination increased the positive rate to 92.5%
      (62/67). Vaccinated children had higher neutralizing (Nt) antibody responses and,
      among IgM-negative patients, all 4 vaccinated children had high Nt antibodies
      while all 10 unvaccinated children had negative or low Nt results. The IgM
      antibody test was proved to be a sensitive method for laboratory confirmation of
      measles virus infection in developing countries.

PMID- 9270729
TI  - Geophagy (soil consumption) and iron supplementation in Uganda.
AB  - Despite the often limited awareness of geophagy, the deliberate consumption of
      soil by humans, it is common in certain areas of the world. This paper reports
      the mineralogical and geochemical composition of geophagical materials collected
      from Uganda, and indicates the potential of such soils in supplying iron to the
      geophagist. In countries like Uganda where modern pharmaceuticals are either
      unobtainable or prohibitively expensive, ingested soils may therefore be very
      important as a mineral supplement for the health of individuals providing they
      are consumed sensibly. Alongside this argument is the fact that individuals in
      such poor countries are frequently iron-deficient.

PMID- 9270730
TI  - Geophagy among school children in western Kenya.
AB  - A cross-sectional study was conducted among 285 school children aged 5-18 years
      in Nyanza Province, Western Kenya, to determine the prevalence of geophagy and
      the types and amounts of soil eaten. Stool samples were taken from a subsample of
      53 (19%) and their silica content determined to compare the results with the
      reported geophagy. Geophagy was practised by 73% of the children. The prevalence
      decreased with age for both sexes up to age 15, then remained stable for girls
      between 15 and 18 years but continued to decrease for boys in that age range.
      Most children ate soil from the surface of termitaria; others preferred the edges
      of paths and gullies, material from the wall of huts, and a chalk-like, soft
      stone commonly found in the area. The soil was eaten dry and was occasionally
      ground, but not processed in other ways. All but 4 of the children practising
      geophagy reported to eat soil at least once daily. The median amount reported
      eaten was 28 g daily, ranging from 8 to 108 g. The reported amount of soil eaten
      daily was significantly correlated to the results of the stool silica
      determinations. Using the median of 1% silica of faecal wet weight as a cut-off
      point to distinguish geophageous children from non-geophageous, the examination
      of a single stool sample had a sensitivity of 76% and a specificity of 80% to
      detect a geophageous child compared to the interview method. The cultural context
      of geophagy and its potential health impact in terms of infection and nutrition
      need to be further investigated, and it is suggested that more school and
      community-based studies on geophagy in different societies should be undertaken.

PMID- 9270731
TI  - Artemether treatment of recrudescent Plasmodium falciparum malaria in children.
AB  - Intramuscular artemether given for five days was evaluated prospectively in 32
      patients with acute recrudescent Plasmodium falciparum malaria. All patients had
      experienced one or more treatment failures with one or more courses of the
      following drugs: chloroquine, amodiaquine, sulphadoxine-pyrimethamine and
      erythromycin given alone or in combination. There was a prompt response to
      treatment with fever and parasite clearance times of 10.7 (3.6) h (range 6-24)
      and 32.3 (8.3) h (range 24-48) respectively. Parasite reduction at 24 h was 93.2
      (7.8)% (range 75-100). The cure rate on day 14 was 100%. The drug was well
      tolerated. These results suggest that artemether is rapidly effective in acute
      recrudescent Plasmodium falciparum malaria and is without deleterious side
      effects.

PMID- 9270732
TI  - Antigenicity and specificity of very low molecular weight Onchocerca volvulus
      polypeptides in the range 2.2-12.5 kD.
AB  - Onchocerca volvulus polypeptides in the molecular mass range of 2.2 to 12.5 kD
      were separated by Tricine-SDS-PAGE and the serological recognition of these very
      low molecular weight antigens (VLMW-OvAg) was then investigated by immuno
      blotting. Sera from 21 onchocerciasis patients as well as from 53 individuals
      with other filariases were used to determine the sensitivity and specificity of
      detection of individual VLMW-OvAg. In onchocerciasis patients, up to 16 VLMW-OvAg
      were recognized predominantly by IgG1 and IgG4, while only few antigens were
      recognized by IgG2 and IgG3. The antigen recognition pattern varied individually,
      but 4 VLMW-OvAg of 8.6, 6.2, 5.4, and 5.1 kD, respectively, were bound by IgG4
      from more than 90% of the onchocerciasis patients. Six VLMW-OvAg of 7.3, 5.8,
      5.4, 4.0, 3.8, and 3.6 kD were recognized exclusively by IgG1 from onchocerciasis
      patients. In amicrofilaraemic filariasis patients with lymphatic pathology, a
      strong reactivity of IgG3 to an OvAg of 2.2 kD was observed, indicating a
      possible contribution of this antigen to the pathogenesis. In the molecular mass
      range below 13 kD, no specific carbohydrate residues or phosphorylcholine
      containing (PC) determinants could be identified by lectin-blotting or PC
      specific immunoblotting, respectively. Two-dimensional separation and
      immunoblotting distinctly resolved more than 40 antigenic polypeptides, the
      majority focusing at acidic isoelectric points. In O. volvulus-infected
      chimpanzees the IgG1- and IgG4-reactivity against OvAg below 13 kD appeared
      concurrently with onset of patent infection. These data suggest that some of
      these VLMW-OvAg might be associated with the production and release of
      microfilariae from gravid female worms as well as be involved in immune-mediated
      pathogenesis during filarial infections.

PMID- 9270733
TI  - A health insurance scheme for hospital care in Bwamanda District, Zaire: lessons
      and questions after 10 years of functioning.
AB  - A voluntary insurance scheme for hospital care was launched in 1986 in the
      Bwamanda District in northwest Zaire. The paper briefly reviews the rationale,
      design and implementation of the scheme and discusses its results and performance
      over time. The scheme succeeded in generating stable revenue for the hospital in
      a context where government intervention was virtually absent and external
      subsidies were most uncertain. Hospital data indicate that hospital services were
      used by a significantly higher proportion of insured patients than uninsured
      people. The features of the environment in which the insurance scheme thrived are
      discussed and the conditions that facilitated its development reviewed. These
      conditions comprise organizational-managerial, economic-financial, social and
      political factors. The Bwamanda case study illustrates the feasibility of health
      insurance-at least for hospital-based inpatient care-at rural district level in
      sub-Saharan Africa, but also exemplifies the managerial and social complexity of
      such financing mechanisms.

PMID- 9270734
TI  - Cytokine levels during mild and cerebral falciparum malaria in children living in
      a mesoendemic area.
AB  - Cell-mediated immunity and cytokines are probably involved in the pathogenesis of
      malaria. To investigate the role and the activity of different immune cells, we
      measured levels of tumour necrosis factor-(TNF-alpha), gamma interferon (IFN
      gamma) and several interleukins (IL-2, IL-4, IL-6 and IL-10) in children with
      mild (MM) and cerebral (CM) Plasmodium falciparum malaria and compared them with
      those of healthy children from Guadalupe--Lobata District, St. Tome Island, where
      malaria is mesoendemic. Both groups of patients had significantly higher levels
      of IL-6, IL-10 and TNF-alpha than controls. For IL-2, IL-4 and IFN-gamma we found
      no difference between the groups. However, 24 h after admission the levels of IL
      10 and IL-6 were significantly higher in CM than in MM patients, although 7 days
      after treatment they returned to normal levels, similar to those found in control
      children. Therefore, TNF-alpha IL-6 and IL-10 increase during Plasmodium
      falciparum attacks in all children, not only in those with cerebral malaria. This
      finding suggests the activation of the monocyte/macrophage system during the
      early stage of clinical malaria.

PMID- 9270735
TI  - Circulating anodic and cathodic antigen in serum and urine of mixed Schistosoma
      haematobium and S. mansoni infections in Office du Niger, Mali.
AB  - In Office du Niger, an area endemic for both Schistosoma haematobium and S.
      mansoni in Mali, circulating anodic (CAA) and cathodic (CCA) antigen detection
      assays were performed on pretreatment serum and urine samples from two villages,
      Rigande and Siguivouce, and compared with egg counting methods. The highest
      prevalence was obtained with the urine-CCA assay which also had the highest
      sensitivity to S. haematobium, S. mansoni or mixed infection. A single urine-CCA
      assay was as sensitive as repeated egg counts (one stool+two urine examinations
      per individual). When the different assays were tested in parallel, several
      combinations including assays on serum were found to be highly sensitive. As
      urine sampling is widely accepted, urine assays will be used for further
      monitoring these villages one and two years after chemotherapy.

PMID- 9270736
TI  - Diethylcarbamazine: effect on lysosomal enzymes and acetylcholine in Wuchereria
      bancrofti infection.
AB  - We measured the levels of lysosomal enzymes and acetylcholine in Wuchereria
      bancrofti-infected asymptomatic microfilaraemic human serum, and found a
      significant decrease in the activity of beta-glucuronidase and acid phosphatase
      compared to normal serum. Acetylcholine levels were also decreased during
      infection. However, after giving diethylcarbamazine (6 mg/kg body wt/day) the
      level of lysosomal enzymes and acetylcholine increased and reached a normal value
      after two weeks of therapy. It is proposed that parasites secrete
      acetylcholinesterase in the circulation which degrades acetylcholine. Since
      acetylcholine stimulates the release of lysosomal enzymes and phagocytosis, the
      immune response of the host is suppressed during infection. During
      diethylcarbamazine (DEC) therapy the parasitic enzyme is inhibited by the drug
      and the normal level of acetylcholine is resumed, which again stimulates the
      release of lysosomal enzyme and the process of phagocytosis.

PMID- 9270737
TI  - pOVEX vector: prokaryotic expression and purification of onchocerciasis vaccine
      candidate antigens as fusion proteins with the 24 kD Onchocerca volvulus
      glutathione S-transferase.
AB  - An expression vector, pOVEX, has been designed and constructed, combining the
      advantages of the expression vectors pGEX-3X and pJC2o. The pOVEX vector produces
      a fusion protein with the 24 kD Onchocerca volvulus glutathione S-transferase
      (OvGST2) which is easy to purify in one step from bacterial extracts under non
      denaturing conditions using glutathione-sepharose chromatography. High yields of
      fusion protein were produced from this T7 RNA polymerase-dependent expression
      vector, which were then cleaved by digestion with the factor Xa protease to
      separate the OVGST2 polypeptide from the expressed protein of interest. This
      vector will be particularly useful to O. volvulus investigators for the
      production of O. volvulus antigens for the analyses of host humoral and cellular
      responses to these proteins and for immunization studies.

PMID- 9270738
TI  - A population-based coprological study of human fascioliasis in a hyperendemic
      area of the Bolivian Altiplano.
AB  - The community of Chijipata Alta, at an altitude of 3850 m, near the southern
      coast of Lake Titicaca in the northern Altiplano of Bolivia, was surveyed for
      human fascioliasis. The global prevalence (66.7%) and intensity (eggs per gram of
      faeces--epg: range: 24-4440; arithmetic mean: 1001; geometric mean: 390) proved
      to be the highest known in the world by means of coprological techniques. These
      results suggest the existence of highly hyperendemic subzones among the large
      human fascioliasis-endemic zone of the Bolivian northern Altiplano. Despite the
      decrease in prevalence and intensity from children (75.0%, 24-4440 epg) to adults
      (41.7%, 144-864 epg), our findings show that in an hyperendemic zone adult
      subjects either maintain the parasites acquired when young or are newly infected
      as the consequence of inhabiting a zone of high infection risk.

PMID- 9270739
TI  - Coping with Africa's increasing tuberculosis burden: are community supervisors an
      essential component of the DOT strategy? Directly observed therapy.
AB  - Tuberculosis incidence in Africa is increasing dramatically and fragile health
      systems are struggling to cope. Potential coping capacity may lie within affected
      communities but this capacity needs to be harnessed if tuberculosis is to be
      controlled. Since 1991 all patients with tuberculosis in Hlabisa health district,
      South Africa have been eligible for community-based directly observed therapy
      (DOT). Patients are supervised either by a health worker (HW) in a village
      clinic, or in the community by a community health worker (CHW) or a volunteer lay
      person (VLP). Tuberculosis incidence increased from 312 cases in 1991 to 1250
      cases in 1996. By December 1995, 2622 (87%) of 3006 patients had received DOT,
      supervised mainly by VLP (56%) but also by HW (28%) and CHW (16%). The proportion
      supervised by HW fell from 46% in 1991 to 26% in 1995 (P < 0.0001). More patients
      supervised by VLP (85%) and CHW (88%) than by HW (79%, P = 0.0008) completed
      treatment. Case-holding by HW declined more between 1991 and 1995 (84% to 71%, P
      = 0.02) than did case-holding by both CHW (95% to 90%. P = 0.7) and VLP (88% to
      84%, P = 0.4). Mortality was similar (4-6%) and stable over time, irrespective of
      the supervisor. High tuberculosis treatment completion rates are achievable and
      sustainable for several years in resource-poor settings despite a massively
      increased case load if community resources are harnessed. Patients may be more
      effectively supervised by voluntary lay people than by health workers under these
      circumstances, without being placed at increased risk. These findings suggest
      that community supervisors may be an essential component of any DOT strategy.

PMID- 9270740
TI  - Compliance with malaria chemoprophylaxis and preventative measures against
      mosquito bites among Dutch travellers.
AB  - Self-reported compliance with a malaria chemoprophylaxis regimen of proguanil
      (PG) plus chloroquine (CQ) was assessed in a cohort of 547 Dutch travellers who
      visited a single travel clinic when travelling to various areas endemic for
      falciparum malaria. 503 (92%) had taken PG/CQ prophylaxis, but only 326 (60%)
      reported regular and uninterrupted use throughout the journey and 4 weeks
      afterwards. Compliance differed by travel destination and was 45% in South
      America, 52% in West Africa, 53% in South-east Asia, 60% in the Indian
      Subcontinent and 78% in East Africa. Parasitologically confirmed falciparum
      malaria occurred in 5 travellers (0.9%), including 3 of 24 non-compliant
      travellers to West Africa (12.5%). Apart from destination, independent risk
      factors for non-compliance were young age, extensive travel experience and
      adventurous travel. Compliance with protection against mosquito bites was 80% for
      wearing long-sleeved shirts and long-legged trousers after sunset, 73% for use of
      repellents, 56% for sleeping under bed nets and 37% for keeping the sleeping
      quarters free of mosquitoes. Although 440 travellers (80%) reported to have taken
      two or more of these measures at least once, only 88 (16%) had done so on a daily
      basis. Daily use of bed nets was reported more frequently among subjects who were
      non-compliant with chemoprophylaxis. Compliance regarding malaria
      chemoprophylaxis should be improved, particularly in high-risk areas such as Sub
      saharan Africa, with extra attention to young, adventurous travellers. More
      emphasis should be placed on prevention of Anopheles bites.

PMID- 9270741
TI  - An open multicenter trial of conversion from Sandimmun to Neoral in stable kidney
      transplant patients.

PMID- 9270742
TI  - Perforin intracytoplasmic expression by peripheral blood lymphocytes in renal
      transplantation.

PMID- 9270743
TI  - Functional and pathologic outcome after complement inactivation in a pig kidney
      human blood xenoperfusion model.

PMID- 9270744
TI  - Circulating ICAM-3 (CD 50) levels after kidney transplantation.

PMID- 9270745
TI  - Proton NMR spectroscopy as a novel approach to the monitoring of citrate and
      trimethylamine-N-oxide excretion after kidney preservation.

PMID- 9270746
TI  - French multicenter study of Neoral conversion in heart transplant patients.

PMID- 9270747
TI  - Oxidized LDL, T lymphocytes, and graft atherosclerosis.

PMID- 9270748
TI  - Clinical significance of T cell monitoring during antithymocyte globulin
      induction in renal transplantation.

PMID- 9270750
TI  - Comparative study of two methods of HLA-DR typing: serology and PCR/Dot Blot
      Reverse.

PMID- 9270749
TI  - Effect of HLA compatibility on liver transplantation: is it a predictive factor
      of postoperative outcome?

PMID- 9270751
TI  - Removal of anti-Gal alpha (1,3)Gal antibodies diminishes the cytotoxic effect of
      primate xenoreactive antibodies on rat endothelial cells.

PMID- 9270752
TI  - Consequences of cold and warm ischemia on pulmonary mitochondrial respiratory
      function.

PMID- 9270753
TI  - Improved functional parameters of liver perfusion with a complete medium.

PMID- 9270755
TI  - Role of donor characteristics on long-term renal allograft survival.

PMID- 9270754
TI  - Beneficial effect on rat kidney preservation of the antiischemic agent
      trimetazidine during cold storage and reperfusion: assessment by 31P nuclear
      magnetic resonance spectroscopy.

PMID- 9270756
TI  - Outcome of liver grafts with more than 10 hours of cold ischemia.

PMID- 9270757
TI  - Influence of cyclosporin A on the damage and regeneration of the kidney after
      severe ischemia/reperfusion injury.

PMID- 9270759
TI  - BTI-322 for acute rejection after renal transplantation.

PMID- 9270758
TI  - Stable mixed chimerism induced by total lymphoid irradiation or by total body
      irradiation is maintained by different mechanisms and leads to different graft
      versus leukemia or graft rejection reactions.

PMID- 9270760
TI  - Rejection of cardiac xenografts by NK cells and macrophages.

PMID- 9270761
TI  - Long-term survival of hamster-to-rat heart xenografts based on mechanisms of
      accommodation and tolerance of CD5 B cells.

PMID- 9270762
TI  - Intrathecal allograft of chromaffin cells for intractable pain treatment: a model
      for understanding CNS tolerance mechanisms in humans.

PMID- 9270763
TI  - High-energy phosphate and ventricular function in rat hearts during 12-hour
      continuous microperfusion at 4 degrees C: effect of oxygenation.

PMID- 9270765
TI  - Renal transplantation in patients with systemic lupus erythematosus: a
      multicenter study.

PMID- 9270766
TI  - Long-term results of combined kidney and liver transplantation at one center.

PMID- 9270764
TI  - Beneficial effects of a low-potassium+ and polyethylene glycol solution on renal
      function and structure during 48-hour cold storage preservation.

PMID- 9270767
TI  - Long-term metabolic control in pancreas transplant patients (follow-up 3 to 13
      years).

PMID- 9270769
TI  - Microsatellites in the HLA region: potential applications in bone marrow
      transplantation.

PMID- 9270768
TI  - High-titered anti-HBs fresh frozen plasma for immunoprophylaxis against hepatitis
      B virus recurrence after liver transplantation.

PMID- 9270770
TI  - Lipoprotein glomerulopathy: a new apolipoprotein-E-related disease that recurs
      after renal transplantation.

PMID- 9270771
TI  - CD2 induced apoptosis of peripheral T cells.

PMID- 9270772
TI  - Treatment of gingival hyperplasia secondary to cyclosporine by the new macrolide
      azithromycin.

PMID- 9270773
TI  - Prophylactic administration of prostaglandin E1 in liver transplantation: results
      of a pilot trial.

PMID- 9270774
TI  - Rebound in complement-dependent cytotoxicity and antibody-dependent cell-mediated
      cytotoxic activity in primate serum after pig liver perfusion.

PMID- 9270776
TI  - Hepatic stellate cells reversibly express alpha-smooth muscle actin during acute
      hepatic ischemia.

PMID- 9270775
TI  - Detection of human cytomegalovirus in renal transplantation: comparison of four
      diagnostic methods: DNA in sera by polymerase chain reaction (PCR), DNA in
      leukocyte by PCR, pp65 leukocytic antigenemia, and viremia.

PMID- 9270777
TI  - In vitro immunomodulation of human islet allografts using mixed islet lymphocyte
      coculture.

PMID- 9270778
TI  - Docosahexaenoic and eicosapentaenoic acids inhibit in vitro human lymphocyte
      proliferation induced by allogenic cells.

PMID- 9270779
TI  - Kidney transplantation in highly sensitized patients.

PMID- 9270780
TI  - Prevalence and clinical significance of antiphospholipid antibodies in renal
      transplant recipients.

PMID- 9270781
TI  - Losartan decreases hemoglobin in renal transplant recipients.

PMID- 9270782
TI  - Effect of cyclosporine on serum lipoprotein(a) levels in renal transplant
      recipients.

PMID- 9270783
TI  - Hepatic cirrhosis and kidney transplantation outcome.

PMID- 9270784
TI  - Treatment of posttransplant erythrocytosis with losartan.

PMID- 9270785
TI  - Lung granulomatous pneumocystosis after kidney transplantation: an uncommon
      complication.

PMID- 9270786
TI  - What is the risk of transferral of an undetected neoplasm during organ
      transplantation?

PMID- 9270787
TI  - Histological assessment of combined chemoembolization and alcoholization
      [corrected] for hepatocellular carcinoma in cirrhotic patients.

PMID- 9270788
TI  - Management of hepatic artery complications after orthotopic liver
      transplantation.

PMID- 9270789
TI  - Three cases of liver transplantation for type I familial amyloid polyneuropathy.

PMID- 9270790
TI  - Potential role of von Willebrand factor in pancreatic venous thrombosis in
      simultaneous kidney and pancreas transplantation.

PMID- 9270791
TI  - Human islet autotransplantations: new indications.

PMID- 9270792
TI  - Long-term outcome of pancreas transplantation.

PMID- 9270793
TI  - Prevention of rejection with BTI-322 after renal transplantation (results at 9
      months).

PMID- 9270795
TI  - Comparative study of chronic ambulatory peritoneal dialysis versus hemodialysis
      patients after kidney transplantation: clinical and financial assessment.

PMID- 9270794
TI  - A prospective study on efficacy and tolerance of antithymocyte globulin Fresenius
      versus thymoglobuline Merieux after renal transplantation.

PMID- 9270796
TI  - Removal of kidneys from living donors: technical or ethical problem?

PMID- 9270797
TI  - Brain death management: keystone of transplantation activity.

PMID- 9270798
TI  - Results of kidney transplantation in nonresident patients: a retrospective study.

PMID- 9270799
TI  - Reluctance in organ donation: a plea to re-target the information campaigns.

PMID- 9270800
TI  - Kinetics of permeation of 2,3-butanediol on isolated perfused rat kidney model
      assessed by proton nuclear magnetic resonance spectroscopy.

PMID- 9270801
TI  - Expression of aldehydic lipid peroxidation products in rat kidneys during warm
      ischemia.

PMID- 9270802
TI  - Calcium antagonists improve kidney function in the rat after cold storage in high
      Na UW but not in high-K UW solution.

PMID- 9270803
TI  - Performances of Doppler echocardiography for diagnosis of acute, mild, or
      moderate cardiac allograft rejection.

PMID- 9270804
TI  - Outcome of HBs antigen positive kidneys after renal transplantation.

PMID- 9270805
TI  - A specific alteration of protein enzymatic glycosylation induced by cyclosporine.

PMID- 9270807
TI  - Improved absorption and bioavailability of cyclosporine A from a microemulsion
      formulation in lung transplant recipients affected with cystic fibrosis.

PMID- 9270806
TI  - Switching conventional cyclosporine treatment to microemulsion formulation in
      patients who need three divided doses.

PMID- 9270808
TI  - Successful pregnancy 5 years after cardiac transplantation for peripartum
      cardiomyopathy.

PMID- 9270809
TI  - Pregnancy outcome in kidney allograft recipients.

PMID- 9270810
TI  - Thirty-three pregnancies in a population of 1725 renal transplant patients.

PMID- 9270811
TI  - Immunosuppressive drugs and pregnancy: experimental and clinical data.

PMID- 9270812
TI  - Immunological tolerance of the fetal allograft: efficacy of immunotherapy and IL
      4 and TNF alpha serum levels in recurrent abortion.

PMID- 9270813
TI  - Pregnancy after liver transplantation: focusing on risks to the mother.

PMID- 9270815
TI  - Transplant and fetus: how do they coexist in the maternal mind?

PMID- 9270814
TI  - Pregnancy in renal transplant patients: 45 case reports.

PMID- 9270816
TI  - Immunological tolerance following stem cell transplantation in human fetuses in
      utero.

PMID- 9270817
TI  - Pregnancy in kidney transplantation: past and present experience.

PMID- 9270818
TI  - Pregnancy in renal transplantation: a pediatric unit report.

PMID- 9270819
TI  - Analysis of 629 pregnancy outcomes in transplant recipients treated with
      Sandimmun.

PMID- 9270820
TI  - Pregnancy after cardiac transplantation.

PMID- 9270821
TI  - Biological activity of tacrolimus (FK506) and its metabolites from whole blood of
      kidney transplant patients.

PMID- 9270822
TI  - Comparison of cyclosporine A and FK506 with regard to complaints and psychosocial
      characteristics before and after liver transplantation.

PMID- 9270823
TI  - Effect of cyclosporine A treatment in vitro on pancreatic islet allograft
      rejection.

PMID- 9270825
TI  - Three-year follow-up of the European Multicenter Tacrolimus (FK506) Liver Study.

PMID- 9270824
TI  - Triple drug treatment with cyclosporine, leflunomide and mycophenolate mofetil
      prevents rejection of pig islets transplanted into rats and primates.

PMID- 9270826
TI  - Hyper-response to exogenous insulin in diabetic rats after islet
      allotransplantation, without reversion of diabetes.

PMID- 9270827
TI  - Role of screening colonoscopy in elective liver transplantation evaluation.

PMID- 9270828
TI  - Recurrent hepatic sarcoidosis following liver transplantation.

PMID- 9270829
TI  - A historical review of fish vaccinology.
AB  - The first report on fish vaccination to appear in a widely read international
      scientific journal was that by Duff [5] dealing with his results obtained with
      anti-furunculosis vaccines. Duff's report did not result in an immediate
      landslide of fish vaccination trials in other laboratories because, in the years
      following the second world war, the preoccupation was with disease control using
      the newly discovered antibiotics. In fish culture, the ensuing 30 to 40 years
      might accurately have been termed the "era of chemotherapy" because large numbers
      of antibiotics, sulpha drugs, and even mercury-based antimicrobial agents were
      routinely used. It was only in the mid to late 1970s, with an increased interest
      in fish farming, particularly marine fish farming, that attention was once again
      turned to the possibility of vaccination as a means of preventing/ controlling
      fish diseases and to the development of commercially available vaccines. The
      reasons for this turn of events were varied: the high cost of using chemotherapy,
      the short-term nature of the protection obtained with antibiotics, the increasing
      appearance of antibiotic resistant fish pathogens, and, to some extent, concerns
      about the environmental impacts of antibiotic use. This paper briefly outlines
      the success that has attended efforts to develop vaccines against some of the
      more important bacterial diseases of cultured fish and the progress made in
      developing vaccines against important viral fish pathogens. In the process, an
      attempt will be made to show how fish vaccine development has benefited from an
      improved knowledge of the fish's immune system and from a better understanding of
      the virulence factors possessed by particular fish pathogens.

PMID- 9270830
TI  - The adaptive immune system of fish.
AB  - Fish above the level of the agnatha display typical vertebrate adaptive immune
      responses characterized by immunoglobulins, T-cell receptors, cytokines, and
      major histocompatibility complex molecules. However, while the immune system of
      fish is quite different in its efficiency and complexity from that of higher
      vertebrates, our knowledge is sufficiently limited that we do not yet have a full
      understanding of the reasons for this difference. Filling the substantial gaps in
      our knowledge of the adaptive immune responses of fish will improve our
      understanding of their response to vaccines, and aid in the rational design of
      vaccines and protocols for vaccination.

PMID- 9270831
TI  - Immunity in fish larvae.
AB  - The route of immunization, dose and nature of antigens are relevant for induction
      of specific immune responses but they are particularly influenced by the state of
      immunomaturation of fish. It is difficult, however, to determine when the fish
      immune system has matured and, accordingly, when the fry can be successfully
      vaccinated. To establish some general parameters which can correlate the
      development of protective immunity with maturation of the immune system we
      review: (i) the appearance of first lympho-haemopoietic cell precursors; (ii) the
      histological and functional maturation of lymphoid organs; (iii) the relevance of
      phagocytosis and transport of maternal Ig to eggs for early vaccination; (iv) the
      appearance of both T-like and B-like cells and their correlation with the
      development of the cell-mediated and humoral immune responses and (v) the
      mechanisms which may be involved in the induction of tolerance following early
      immunization of fry. These data rather than a general rule for vaccination of
      larval fish indicate that the earliest age (size) that a fish can be vaccinated
      differs between species and vaccines.

PMID- 9270832
TI  - Environmental effects on fish immune mechanisms.
AB  - Environmental stress factors which influence fish immune (and likely many other
      physiological) functions can be divided into two broad, but not mutually
      exclusive, categories, namely those which occur naturally and those which are
      artificial. Natural environmental stress factors include season, temperature,
      salinity and photoperiod as well as social stress factors such as crowding and
      hierarchy. In general, artificial environmental stress factors are man made, and
      mainly involve pollutants such as acid rain, heavy metals and organic compounds.
      The available data indicate that regardless of which immune parameters are
      assessed, both natural and artificial environmental stress factors appear to
      suppress immune functions. Of the numerous environmental stress factors
      considered, pollutants, handling/confinement and low temperature are probably the
      best studied forms in fish. All three forms of stress factors have been shown to
      suppress components of both the innate (non-specific) and adaptive arms of the
      immune system. Since immune responses which protect against invading pathogens
      frequently involve interactions between both the innate and adaptive arms of the
      immune system, it seems reasonable to conclude that either acute or chronic
      exposure to stress factors may predispose fish to infectious diseases. Signalling
      mechanisms responsible for the effects of these various stress factors on
      immunity in fish are poorly understood, although elevated serum ACTH and cortisol
      levels appear to be involved in some cases. A better understanding of the
      mechanism(s) resulting in immunosuppression should facilitate future in vivo
      manipulations to reduce susceptibility to disease in aquaculture situations.

PMID- 9270834
TI  - Immune responses after injection vaccination of fish.
AB  - During the last 20 years considerable progress has been made in describing and
      understanding the immune system of fish. Fish are the phylogenetically oldest
      vertebrate group with an immune system showing clear similarities to the defence
      systems of mammals and birds. Both innate immunity (non-specific responses) and
      acquired immunity (specific responses) are important for the defence against
      invading pathogens. Antigen injection will evoke humoral and cellular responses,
      which show the expected characteristics of specificity and memory. Variability in
      the results can be caused by external factors such as antigen dose, temperature
      and handling stress. Moreover, the genetic background of the fish may also play a
      role. The use of standardised inbred fish lines is recommended for the optimal
      development and evaluation of vaccines and vaccination procedures.

PMID- 9270833
TI  - Crustacean immunity--a short review.

PMID- 9270835
TI  - Antigen uptake and immune responses after immersion vaccination.
AB  - Immersion vaccination is an effective and practical method for mass vaccination
      of fish and most commercial bacterins are currently administered by this method,
      even though the exact mechanisms of antigen uptake and protection still remain
      unknown. Immersion vaccination includes several delivery techniques including
      spray, direct immersion, hyperosmotic dip and flush exposure. Various factors
      have been shown to influence the uptake of antigen from a vaccine bath, such as
      the concentration of vaccine, the length of immersion time, size of the fish,
      stress, pH and salt concentration of the vaccine solution, the water temperature,
      anaesthetics, the use of adjuvants, and the physical state (particulate or
      soluble) of the antigen. Among these, the antigen concentration is the most
      important factor for antigen uptake and protection. Recently we found that the
      amount of antigen taken up is correlated with the length of immersion time in
      dilute vaccine solutions. Most authors have suggested the gills as the main site
      of antigen entry, but skin, lateral line and the gut have also been suggested.
      Our quantitative study has shown that the skin is the main site of antigen uptake
      and that there are no differences in rate of uptake between the lateral line and
      the remaining skin of the body surface. Not only phagocytes but also several
      types of epithelial cells are involved in antigen uptake. Cells involved in
      antigen uptake can be different depending on the physical state of the antigen
      and the site of antigen entry. In most trials with immersion vaccination,
      antibodies against pathogens are not detectable in the serum by micro-titration
      and, even when antibodies are found, the titre does not always correlate with
      protection. However, some authors have reported elevated specific antibody levels
      in the serum of fish vaccinated by immersion, and even that protection can be
      successfully conferred by transferring immune plasma. Thus, the role of humoral
      immunity on protection mechanisms after immersion vaccination has been
      controversial and potentially important roles for cell-mediated immunity or local
      immunity have been implicated.

PMID- 9270836
TI  - Antigen uptake and immune responses after oral vaccination.
AB  - Oral delivery of vaccine, with antigen simply mixed with feed, is the easiest
      method of mass vaccination of fish of all sizes. It is time and labour-saving,
      and avoids any manipulation stress. However, large quantities of antigen are
      necessary and it is not possible to know the exact dose absorbed by each fish.
      Moreover the resulting protection is generally weak and of short duration. To
      improve the effectiveness of oral vaccination a considerable amount of work has
      been done in the last 15 years. It is now well established that the second
      segment of the hindgut of fish has the ability to absorb soluble or particulate
      antigens. These antigens reach the intraepithelial macrophages which show
      antigenic determinants on their cell membrane, suggesting an antigen-presenting
      function. Moreover, a gut-associated lymphoid tissue composed of several lymphoid
      cell types, macrophages, granulocytes and plasma cells has been described in this
      region of the gut and recent studies indicate that it is involved in an
      intestinal immune response. Both mucosal and systemic immune responses seem to
      develop as indicated by the presence of antibodies in gut mucus, bile and serum.
      However, these responses are higher following anal delivery of antigen than oral
      delivery. It is generally considered that during oral delivery antigens are
      digested in the foregut and/or in the stomach. Thus studies are being carried out
      now on ways to protect antigens, for instance through the encapsulation of
      antigen, the neutralisation of gastric secretions and the use of oral adjuvants.

PMID- 9270837
TI  - Technical aspects of the administration of vaccines.
AB  - The practise of vaccination as a standard part of fish husbandry has led during
      the last 20 years to the adoption of a number of basic vaccination regimes based
      on an understanding of the principles involved and how to maximize protection.
      The strategies adopted depend on the species of fish, its husbandry, the disease
      against which protection is sought and the optimum timing within the growth cycle
      so that the predicted duration of protection coincides with the timing of any
      expected disease challenge. These and other parameters influencing the
      performance of vaccines are discussed in the context of what is practical and
      cost-effective in each circumstance and the risks involved in handling and
      administering vaccine by the different available methods.

PMID- 9270839
TI  - Immunization with bacterial antigens: furunculosis.
AB  - Although the nature of the antigens and the immune responses they elicit to
      achieve immunity to furunculosis are still not well defined, the currently
      available vaccines comprising A. salmonicida bacterins emulsified in oil
      adjuvants and delivered by intraperitoneal injection provide remarkably high
      levels of long-lasting protection. Despite some concern over side-effects, these
      vaccines have been adopted by most Atlantic salmon farmers over the last four
      years, transforming a situation where furunculosis outbreaks were becoming
      catastrophic to one where losses from the disease are negligible. Present
      evidence indicates that antibody responses to the polysaccharide capsule and iron
      regulated outer membrane proteins are associated with protection. Furthermore,
      cell-mediated immune responses involving antigen-induced release of cytokines
      from lymphocytes and the resultant activation of macrophages with the ability to
      kill the pathogen are also considered important protective mechanisms. Vaccines
      comprising whole A. salmonicida cultures grown under iron-restricted conditions
      and delivered by injection in an oil adjuvant are expected to induce prolonged
      stimulation of all the above responses. While these vaccines are suitable and
      effective for administration to salmon smolts there is still a need for mass
      vaccination by immersion or oral routes for salmonid fry. Effective means of
      achieving this are still required.

PMID- 9270840
TI  - Immunization with bacterial antigens: yersiniosis.
AB  - Yersinia ruckeri causes salmonid fish diseases called yersiniosis or enteric
      redmouth disease (ERM). Isolates include several serological varieties and
      disease outbreaks are frequently associated with stress or poor environmental
      factors. As a result, it is difficult to define clearly the significant virulence
      factors and pathogenic mechanisms of the bacterium, which introduces
      uncertainties about the appropriate formulation of bacterins for immunization. An
      enteric redmouth bacterin was the first commercially-produced fish vaccine, and
      the formalin-killed whole-cell product continues to be highly effective whether
      administered by immersion, spray, injection, or oral routes. Serovar 1,
      "Hagerman" strains are the basis for most commercial bacterins, and serovar 2 is
      not included, despite epizootics in chinook salmon and brook trout. Vaccination
      studies report different degrees of cross-protection between serogroups of Y.
      ruckeri, but the basis for the cross-protection is not clear. Lipopolysaccharide
      (LPS) of serovar 1 Y. ruckeri elicits negligible or weak antibody responses in
      fish and low cell-proliferation memory responses compared with serovar 2 strains.
      These observations raise fundamental questions about the kinds of immune
      responses that are involved in the highly effective vaccine-protection provided
      by commercial vaccines.

PMID- 9270838
TI  - Immunization with bacterial antigens: Vibrio infections.
AB  - Within the genus Vibrio, the species causing the most economically important
      diseases in marine culture are Vibrio anguillarum, V. ordalii, V. salmonicida and
      V. vulnificus biotype 2. For these bacterial fish pathogens host range, clinical
      importance, virulence mechanisms, the antigenic variants relevant to vaccination,
      the existence of genetic intraspecific diversity and the available vaccines
      including commercial or domestically produced will be described. Among the 10
      serotypes described in V. anguillarum, only serotypes O1, O2 and O3 have been
      associated with mortality in a great variety of farmed and feral fish worldwide.
      Whereas serotype O1 is a very homogeneous group from the biochemical, serological
      and genetic stand-point, within serotype O2 and O3 two antigenic entities have
      been detected. Moreover these two serotypes present a remarkable genetic
      heterogeneity. However, many of the available commercial vibriosis vaccines
      include in their formulations only V. anguillarum serotype O1 in combination with
      V. ordalii (formerly V. anguillarum biotype 2). In addition no commercial vaccine
      provides information about the subgroup(s) used as representative of V.
      anguillarum O2. Recently, Vibrio species taxonomically related to V. anguillarum
      (VAR) have been isolated from diseased fishes. An extensive characterization of
      these VAR organisms allowed us to distribute them into at least seven O
      serogroups. The inclusion of representative VAR strains in the vibriosis vaccines
      need to be discussed. V. ordalii, V. salmonicida and V. vulnificus are
      homogeneous species with respect to biochemical reactions, serology and degree of
      virulence, possess a narrow host range and seem to be restricted to some
      geographic areas. Although iron acquisition systems can be involved in the
      virulence mechanisms of these pathogens, only in V. anguillarum has it been
      clearly demonstrated that the ability to scavenge iron from the host is a crucial
      virulence determinant. The role of exotoxins and cell surface associated
      properties in the Vibrio infections remains to be elucidated.

PMID- 9270842
TI  - Immunization with bacterial antigens: infections with motile aeromonads.
AB  - Motile aeromonads are a heterogeneous group of organisms which are involved in a
      number of disease syndromes of warm water fish. They are commonly associated with
      bacterial haemorrhagic septicaemia, infectious dropsy, red mouth disease,
      ulcerative conditions etc. A variety of factors has been considered to be
      associated with virulence including haemolysins, proteases, surface array
      protein, acetylcholinesterase etc. We have studied the immune response of Indian
      major carps to antigens of motile aeromonads. The Indian major carp, Labeo
      rohita, showed immunological memory and secondary response on booster
      administration. The extent of protection showed good correlation with titres of
      agglutinating antibody. When polyvalent vaccine was used, the fish showed
      antibody titres against all the component strains. However, the level of antibody
      was less compared to immunization by monovalent vaccines. Cross-reacting
      antibodies induced by monovalent vaccines showed varying degrees of protection.

PMID- 9270841
TI  - Immunization with bacterial antigens: edwardsiellosis.
AB  - Enteric septicaemia of catfish (ESC), caused by Edwardsiella ictaluri, is the
      most serious disease affecting commercial catfish culture in the United States.
      ESC is generally an acute septicaemia that develops very quickly, especially in
      the temperature range of 22-28 degrees C, with a more chronic disease
      presentation outside this range. The ability of E. ictaluri to avoid the host's
      immune system and proliferate into a systemic infection is impressive. Catfish
      kidney tissue cultured positive for E. ictaluri as soon as 15 minutes following
      gastric lavage and signs of disease are observed microscopically within two days
      of immersion challenge, with reported mortalities as early as five days following
      immersion challenge. Analysis of E. ictaluri antigens by several investigators
      using SDS-PAGE and colorimetric western blotting with immune catfish has
      identified as many as 15 immunogenic bands. Analysis using two-dimensional SDS
      PAGE and chemiluminescent western blotting identified 14 bands and 25 spots as
      consistently immunogenic. The strongest immunodominant antigens were reported as
      34-37 KD and 60 KD, depending on the study. Lipopolysaccharide is the only
      purified component of E. ictaluri tested for fish vaccination, and results
      indicated that very poor protection was induced unless Freund's Complete Adjuvant
      was used. Because E. ictaluri strains are serologically homogeneous, most studies
      on vaccination have emphasized killed whole cell preparations and have delivered
      equivocal results. Although antibodies are produced to a variety of preparations,
      a positive antibody response does not correlate with protection unless very high
      titres are achieved. Efficacy of killed products has been demonstrated in field
      trials, and an orally delivered product has been licensed. However, protection
      probably relies on booster exposure of the host to E. ictaluri during non
      permissive temperatures. As a facultative intracellular pathogen, further studies
      on vaccination of catfish against E. ictaluri should target products and delivery
      methods that favour induction of cell mediated immunity.

PMID- 9270843
TI  - Immunization with bacterial antigens: bacterial kidney disease.
AB  - Bacterial kidney disease has consistently resisted attempts to control it by
      prophylactic immunisation. Although successful vaccines have been produced to a
      number of Gram-negative fish pathogens, the relatively simple method used in
      these cases have not been successful with Renibacterium salmoninarum. A more
      circumspect and thorough knowledge of the biological function of R. salmoninarum
      antigens must be obtained. Also required is a more precise understanding of the
      role of regional immunity in effective prophylaxis. Aspects of R. salmoninarum's
      biology provide a provocative challenge to the vaccinologist. Its residence in,
      and apparent commandeering of the macrophage, indicate that a vigorous cell
      mediated response will probably be required to generate protective immunity. Its
      most biologically potent secreted product, p57, appears to be an aggressin.
      Further, p57 has the capability of frustrating immunoprophylaxis by either
      misdirecting the immune response, or by preventing its induction. Many
      immunization studies have used injection immunization and challenge protocols. It
      now appears that alternative routes of immunization which had been considered
      less protective (i.e. oral immunization) may not only be more efficacious, but
      may be the only route that does not lead to a misdirected and possibly
      pathological immune response. Also, the general reliance on serum antibodies as
      the only means to assess immunity is fraught with difficulties, particularly with
      pathogens such as R. salmoninarum. Recent advances in the analysis of cellular
      immunity will be a great aid in the design of future vaccines.

PMID- 9270844
TI  - Immunization with bacterial antigens: infections with streptococci and related
      organisms.
AB  - Streptococcal infections of fish have been reported from various parts of the
      world, including the Far East, the United States, South Africa, Australia, Israel
      and Europe. Classification of Gram-positive cocci (DNA-DNA hybridization studies
      coupled with 165 sequencing) has shown that at least five different defined
      species are pathogenic to fish, e.g. Streptococcus iniae (syn. S. shilot),
      Streptococcus difficile, Lactococcus garvieae (syn. Enterococcus seriolicida),
      Lactococcus piscium and Vagococcus salmoninarum. "Streptococcosis" of fish should
      therefore be regarded as a complex of similar diseases caused by different genera
      and species of Gram-positive cocci, each capable of inducing CNS damage, as well
      as various degrees of multisystem organ involvement. Panophthalmitis ("pop-eye")
      and meningitis/meningoencephalitis are the sole findings in trout infected by S.
      iniae and in tilapines infected by S. difficile. In contrast, L. garvieae
      infected trout bear a systemic hyperacute infection with diffuse haemorrhages.
      Therapeutic measures are generally ineffective. Development of vaccines is
      therefore essential to control these diseases. In our studies, trout were
      vaccinated intraperitoneally with whole-cell formalin-inactivated S. iniae and L.
      garvieae and tilapines with whole-cell formalin-inactivated and acellular S.
      difficile extract. Under laboratory conditions, S. difficile-vaccinated tilapines
      were protected against a challenge of 100 LD50s. Protection was correlated with
      the development of specific agglutinins. Western blot analysis supported the
      hypothesis that only a few proteins act as protective antigens. S. iniae
      autovaccines were effective in preventing the disease in rainbow trout in Israel.
      Under field conditions, fish vaccinated at 50 g were protected for over four
      months. The qualitative analysis of the humoral response indicated that specific
      antibodies are directed against a few protein moieties. The fact that passive
      transfer of antibodies protected fish from experimental infection suggests that
      the basic mechanism of protection is antibody mediated. L. garvieae autovaccines
      developed for Italian trout farming were found to elicit a response similar to
      that of S. iniae. Despite the high virulence of L. garvieae (LD50 of 6 x 10(1)
      CFU/fish, compared with 3 x 10(4) CFU/fish of S. iniae), the protection against
      the experimentally induced disease lasted for five months under laboratory
      conditions, with survival rates of 80-90%. A single injection of the vaccine (0.1
      ml/fish) resulted in specific antibody production detectable for six months. In
      the field, protection rates of 70-80% were obtained for a period of three months,
      in fish of 200-300 g reared at water temperatures of 18-21 degrees C.

PMID- 9270845
TI  - Immunization with bacterial antigens: piscirickettsiosis.
AB  - Piscirickettsiosis is a septicaemic disease of salmonid fish caused by the
      obligated intracellular rickettsia, Piscirickettsia salmonis. This disease was
      first reported in 1989 in salmon cultured in sea water netpens in southern Chile
      where it is still a major problem causing high mortality among cultured
      salmonids. In recent years related agents have been reported in farmed salmonids
      from Ireland, Canada and Norway. Mortality, however, at these locations has been
      reported to be low. Because of the recent description of piscirickettsiosis and
      its aetiological agent, knowledge about the immune response of fish against this
      organism is limited. At present, there is only one paper in the literature
      dealing with this subject. To standardise challenge methods for testing the
      efficacy of vaccination, lethal dose 50% and infectivity dose 50% were determined
      for coho salmon (Oncorhynchus kisutch) and rainbow trout (O. mykiss) using
      intraperitoneal (i.p.) injections of P. salmonis. Experiments using bath
      challenge methods failed to reproduce the disease using rainbow trout although
      low levels of infection in their tissues were found. In a field trial, using
      formalin killed bacterins injected i.p. into pre-smolt coho salmon, the fish were
      naturally challenged by placing them in sea water where endemic
      piscirickettsiosis occurred. The results showed that some of the vaccinated fish
      groups experienced lower cumulative mortality than the non-vaccinated control
      group (X < 0.05), suggesting an immunoprotective response in these animals. A
      trial was also conducted with formalin-killed bacterins in rainbow trout using
      different antigen concentrations with and without booster injections. Fish were
      challenged by IP injection of P. salmonis. Vaccinated fish showed less mortality
      than their respective infected control. Unfortunately the challenge was not
      strong enough because mortality in the infected control fish was low (20%).
      Antibody levels measured by radio-immuno-assay increased until day 40 post
      vaccination. The highest levels of antibody were obtained in the sera of fish
      vaccinated with concentrated antigen using booster injections.

PMID- 9270846
TI  - Immunization with bacterial antigens: pasteurellosis.
AB  - Pasteurella piscicida is the aetiological agent of pasteurellosis or
      pseudotuberculosis, one of the most threatening diseases of wild and cultured
      marine fish. This bacterium has been reported from many geographical areas
      including USA, Japan, and the Mediterranean countries. In this review, the
      biochemical, serological, and molecular characteristics of the pathogen are
      described. In addition, its main virulence mechanisms, such as the presence of
      capsule, the iron uptake system, and the phospholipase activity, as well as their
      putative role in the pathogenicity of P. piscicida are also discussed. Finally, a
      detailed survey of the strategies for controlling the disease is performed, with
      a special emphasis on the vaccination programmes and the most effective
      protective antigens to be included in the vaccine formulations.

PMID- 9270847
TI  - Immunization with bacterial antigens: Flavobacterium and Flexibacter infections.
AB  - Seven bacterial species belonging to the Flavobacterium-Cytophaga group are
      currently considered to be pathogenic for fish. Because they were only recently
      described and/or because the disease they provoke has little economic
      significance, no study has been performed concerning immunization against
      Chryseobacterium scophthalmum, Flavobacterium johnsoniae and Flexibacter
      ovolyticus. Immunization with Flexibacter maritimus has not been investigated,
      and fish surviving a natural infection appear to remain equally susceptible to
      the disease during subsequent outbreaks. On the other hand, interesting data are
      available concerning immunization against Flavobacterium branchiophilum,
      Flavobacterium columnare and Flavobacterium psychrophilum because these bacterial
      species have been known for many years and are responsible for heavy losses in
      many countries. Surviving fish are usually protected against further infection by
      the same pathogens. Extensive serological studies have been performed and
      virulence mechanisms have also been investigated. The review of immunization
      trials against these three bacterial species shows important variations depending
      on the species of fish and the route of administration, but in several cases
      vaccinated fish were successfully protected by high titre of specific antibodies.
      However, no vaccine is commercially available.

PMID- 9270848
TI  - Immunization with viral antigens: infectious pancreatic necrosis.
AB  - Clinical IPN has traditionally been observed in brook trout (Salvelinus
      fontinalis) and rainbow trout (Oncorhynchus mykiss). However, during the past 10
      years outbreaks of IPN have been reported frequently in farmed Atlantic salmon
      (Salmo salar L.) in Norway. Acute IPN with high mortality is observed in fry at
      start feeding and in smolt in the first six months after transfer to seawater.
      Today IPN is the most important infectious disease in Norway in farmed fish,
      giving economic losses of about 60 million USD yearly. A prophylactic strategy
      against this disease is strongly needed. Different strategies for developing IPN
      vaccines have been tested since the virus was first isolated in 1960. Vaccination
      with live virus has not been successful and is probably not an acceptable
      strategy for environmental risk reasons. Vaccination with inactivated virus has
      been tested in rainbow trout given by the oral route, by immersion and injection.
      Protection against challenge was obtained only by injection. IPN vaccines based
      on inactivated virus may be effective but are expensive. A subunit vaccine
      produced by fermentation is a more realistic strategy for fish vaccine production
      if the actual protective epitopes can be identified. Protective IPNV epitopes may
      include both B- and T-cell epitopes, but only B-cell epitopes have been examined
      so far. Epitope mapping with neutralising monoclonal antibodies indicates that
      the internal variable region of VP2 (aa 200-350) folds into an immunodominant
      structure including both serotype specific and conserved neutralisation epitopes
      that can renaturate spontaneously from E. coli-expressed recombinant VP2 (rVP2).
      Analysis with an IPNV group-A specific neutralising monoclonal antibody indicates
      that immunisation with recombinant protein containing the segment (aa 86-210)
      might induce protection against all IPNV serotypes. Subunit vaccines based on E.
      coli-expressed IPNV proteins have been tested in rainbow trout and Atlantic
      salmon. Vaccination by immersion in rainbow trout fry with bacterial lysate from
      E. coli expressing the IPNV Sp strain gene segment A induced protection against
      challenge with the IPNV Buhl strain. By injection of Atlantic salmon parr with
      partly purified E. coli-expressed rVP2 (N1 strain), increased resistance against
      IPN infection was demonstrated by challenge. In field trials it is shown that
      vaccination of pre-smolt with rVP2 included in a commercial oil/glucan adjuvanted
      multivalent bacterial vaccine gives protection against IPN in natural outbreaks,
      compared to fish vaccinated with the same vaccine without the IPNV component.

PMID- 9270849
TI  - Immunization with viral antigens: viral haemorrhagic septicaemia.
AB  - Viral haemorrhagic septicaemia virus (VHSV), is an enveloped negative strand RNA
      virus belonging to the rhabdovirus family. Outbreaks of VHS in farmed rainbow
      trout often lead to very high mortalities and considerable resources are used on
      disease surveillance and trade regulations in Europe to reduce spread of the
      disease. An efficient vaccine would be particular useful in the early stage of
      eradication programmes, as well as in endemic infected areas. Traditional
      vaccines such as killed or attenuated virus have been under development for the
      past 20 years, and although experimental protective properties have been
      demonstrated, no such products have yet fulfilled the requirements for field use.
      In recent years, considerable efforts have been put into development of a
      recombinant subunit vaccine. Focus has been put on the envelope glycoprotein (G
      protein), which has been shown to be the target of neutralizing and protective
      antibodies. Several expression systems have been tried, but so far no products
      have proved superior to the traditional vaccine forms. This paper reviews the
      work related to VHS vaccine development.

PMID- 9270850
TI  - Immunization with viral antigens: infectious haematopoietic necrosis.
AB  - Infectious haematopoietic necrosis (IHN) is one of the most important viral
      diseases of salmonids, especially among juvenile fish where losses can be high.
      For over 20 years, researchers have tested a variety of preparations for control
      of IHN. Early vaccines consisted of killed virus and were effective when
      delivered by injection, but too costly to be practical on a large scale.
      Attenuated vaccines were developed by serial passage in cell culture and by
      monoclonal antibody selection. These offered excellent protection and were cost
      effective, but residual virulence and uncertainty about their effects on other
      aquatic species made them poor candidates for licensing. Subunit vaccines using
      part of the IHNV glycoprotein gene cloned into E. coli or into an attenuated
      strain of A. salmonicida have been tested, appeared safe and were inexpensive.
      These vaccines were reported to provide some protection when delivered by
      immersion. Information on the location of antigenic sites on the glycoprotein led
      to trials using synthetic peptides, but these did not seem to be economically
      viable. Recently, plasmid vectors encoding the glycoprotein gene under control of
      a cytomegalovirus promoter were developed for genetic immunization. The
      constructs were highly protective when delivered by injection, but a more
      practical delivery system is needed. Thus, while several vaccine strategies have
      been tried in order to stimulate specific immunity against IHN, more research is
      needed to develop a commercially viable product for control of this important
      disease.

PMID- 9270851
TI  - Immunization with viral antigens: viral diseases of carp and catfish.
AB  - The viral diseases of carp and catfish for which vaccines have been produced are
      spring viraemia of carp (SVC), grass carp haemorrhage disease (GCHD) and channel
      catfish virus disease (CCVD). Field trials of a commercially produced injectable
      vaccine conducted over several years have shown that carp can be protected
      against SVC. However the supporting data were predominantly qualitative rather
      than quantitative. Large-scale field trials of an experimental oral attenuated
      vaccine against SVC virus over a five year period were successful, and no
      reversion to virulence of the vaccine was recorded. Injectable inactivated and
      attenuated vaccines against GCHD have predominantly been tested under laboratory
      conditions, although a small number of field trials have been reported. In such
      trials of bath and injectable vaccines, survival rates of 50-90% were achieved.
      In China, commercially available vaccines are being used against GCHD. Only
      laboratory trials of vaccines against CCVD have been reported. Bath vaccination
      of eggs of fry with a subunit vaccine and bath immunisation of fingerlings with
      an attenuated virus vaccine have been successful. Problems with current
      approaches and areas for research are discussed.

PMID- 9270852
TI  - Immunization against parasitic diseases of fish.
AB  - Parasitologists have not, in the past, exploited the immune system to protect
      fish against parasitic diseases. In the past few years, however, there has been
      an increased interest in adopting this strategy, and we have made steady and
      promising progress against a few parasites which are of economic importance.
      Amyloodinium ocellatum is an ectoparasitic dinoflagellate on brackish and marine
      fishes, which may also cause problems to aquarium fishes. Antiserum from fish
      inoculated intraperitoneally (i.p.) with living dinospores of the parasite
      immobilizes and agglutinates living dinospores; it also reduces parasite
      infectivity in cell culture. Cryptobia salmositica is a pathogenic
      haemoflagellate of salmonids on the Pacific coast of North America, causing
      mortality in semi-natural and intensive salmon culture facilities. A live
      attenuated vaccine inoculated i.p. protects susceptible juvenile and adult fish
      for at least 24 months. The protection involves production of complement fixing
      antibodies, phagocytosis, and antibody-dependent and antibody-independent T-cell
      cytotoxicity. A monoclonal antibody against a surface membrane glycoprotein (199
      200 kDa is therapeutic in that it significantly reduces parasitaemias when
      inoculated into fish with acute disease. Ichthyophthirius multifiliis is an
      ectoparasitic ciliate of freshwater fishes with world wide distribution, usually
      causing disease when fish are stressed and/or when environmental conditions are
      favourable for parasite multiplication. Live theronts injected into the body
      cavity protect fish, and monoclonal antibodies with immobilizing activity upon
      parasites have been developed. There is some evidence of passive transfer of
      protective immunity from immune to naive fish, and to eggs. Diplostomum
      spathaceum is an intestinal parasite of gulls; the metacercaria stage of the
      parasite encyst and causes disease and mortality in numerous species of
      freshwater fish in Europe and in North America. Fish injected i.p. with
      sonicated/killed cercariae or metacercariae have fewer metacercariae in the eyes
      and survives longer. Lepeophtheirus salmonis and Caligus elongatus are parasitic
      copepods (sea lice), and they are important parasites of Atlantic salmon in cage
      cultures. A vaccine against fish lice is plausible, and the efficacy of about 20
      candidate antigens in protecting fish is being tested.

PMID- 9270853
TI  - Polyvalent vaccines in fish: the interactive effects of multiple antigens.
AB  - Fermentation and cell-grown products commonly used as fish vaccines present a
      relatively crude mixture of antigenic and other immunologically active components
      to the immune system. The specific antigenic make-up and the potential protective
      immunogenicity of this mixture is dependent upon the strain of the pathogen,
      production parameters, inactivation methods, down-stream processing, product
      formulation, storage conditions and the delivery method under which the final
      product is applied. In the past ten years, commercial vaccine products for fish
      have more often consisted of mixtures of multiple products, including two, three,
      four and five vaccines. Such mixtures present an even more extensive and complex
      array of antigens to the immune system. Considering the fact that not all
      antigens stimulate a protective immune response, that antigens vary in their
      immuno-dominance relative to each other and that the immune system of fish has a
      defined and limited capacity to respond to individual antigenic substances, it
      becomes increasingly difficult to formulate these complex mixtures into safe and
      effective commercial products. The clonal capacity of fish to respond to multiple
      antigens may depend on a variety of factors including host species and age, water
      temperature, route of administration and temporal considerations. There is
      growing evidence that antigenic as well as non-antigenic components of vaccines
      can interact synergistically or antagonistically and that they can stimulate,
      cross-react with, inhibit or even suppress the immune response to specific
      antigens. This paper reviews current knowledge about the interactive effects of
      antigenic components of fish vaccines and gives specific examples of how these
      interactions might affect the formulation and performance of multivalent
      products. This paper also considers the potential basis for these interactive
      effects and discusses technical approaches that take advantage of this knowledge
      for the development of new multivalent products.

PMID- 9270854
TI  - Adjuvants and immunostimulants for enhancing vaccine potency in fish.
AB  - Adjuvants combined with immunogens are effective enhancers of the immune response
      in fish. As in other animals, substances such as Freund's complete and incomplete
      adjuvants, light oils and bacterial lipopolysaccharides have been shown to induce
      elevated antibody production when added to bacterins and administered to fish.
      Light oil adjuvants are now used successfully with injectable bacterins of
      Aeromonas salmonicida, and in multivalent fish vaccines where A. salmonicida is
      combined with Yersinia sp., and/or Vibrio spp. antigen preparations. The oils are
      thought to act as depots or reservoirs, holding the antigens in globules at the
      site of injection, thus allowing prolonged dosage. Additions to the oils such as
      muramyl dipeptide, bacterial lipopolysaccharides and other bacterial and animal
      extracted products may activate specific immune cell populations such as T-cells,
      neutrophils and other phagocytic cells important in the cellular mediated
      response. Conjugation of antigens with alum is another traditional approach which
      has been used for A. salmonicida and Y. ruckeri bacterins with varying results.
      The process enables antigen to be held in a reservoir and also may detoxify
      harmful substances. Recent research on substances such as beta-1,3 glucans,
      chitosan, levamisole, and other inflammatory agents shows enhancing effects on
      the specific immune response when added to immunogens and administered by
      injection, bath or by feeding. These substances may also act to elevate non
      specific defence mechanisms against disease agents as most of them are active
      even when given alone.

PMID- 9270856
TI  - Live fish vaccines: history and perspectives.
AB  - In the development of live vaccines against enzootic fish viral diseases, the
      conventional approaches, although somewhat successful, failed finally to deliver
      efficient, safe, and tagged strains for vaccine application. The genetically
      engineered vaccine approach also gave similarly disappointing results. Faced with
      these realities during our work with VHS, we turned our research effort towards
      understanding the molecular basis of virulence and antigenicity of the virus.
      Using sequence analysis of neutralization-escape mutants, we identified several
      amino acid positions on the glycoprotein which seemed to be involved in the
      pathological process. The attenuated phenotype was consistently associated with
      simultaneous mutations at two distant regions, 125-140 and 430-433 of the
      glycoprotein. We also demonstrated that reversion to virulence was accompanied by
      the loss of the concurrent mutations, which confirmed their involvement in
      virulence. The importance of these two regions of the glycoprotein was confirmed
      by the finding that laboratory or naturally attenuated variants had mutations
      within these regions. Using the same methodology, we selected mutants from an
      attenuated temperature resistant variant (tr25), which had previously been
      developed in our laboratory. Virulence, antigenicity and protective activity of
      the further attenuated mutants were evaluated in fish of different size by
      intramuscular (i.m.) or water bath administration. Strains having an additional
      mutation at position 139 were completely non-virulent for fish of 1000-1400
      degree-days (dxd) by bath. These mutants retained their immunogenicity and had a
      thermo-resistant, an antigenic, and five genetic markers. Thus, they will
      constitute ideal candidates for live vaccine development, once their protective
      activity and containment have been confirmed in field trials.

PMID- 9270855
TI  - Fish vaccine antigens produced or delivered by recombinant DNA technologies.
AB  - Current efforts to develop vaccines, particularly for aquacultured species, have
      turned largely to biotechnology because it provides the means to inexpensively
      produce sufficient quantities of the immunoprotective antigen. These efforts have
      resulted in several prototype vaccines for fish and the publication of a large
      number of articles on the subject. However, there are only a few recombinant DNA
      based vaccines for aquaculture in the licensing pipeline. Continued funding of
      research on recombinant DNA vaccines comes from the recognition by industry and
      government funding agencies that this research can lead to an increased
      understanding of the mechanisms in protective immunity. This is especially
      important for fish and shellfish species since our knowledge of the immune
      mechanisms in these animals is pitifully meagre. This presentation discusses the
      relative merits of the different recombinant DNA technologies that have been used
      to produce viral vaccines for fish and the promising approaches that are under
      consideration to increase the efficacy of these vaccines. There are many
      approaches to antigen production by recombinant DNA techniques including: (i) the
      preparation of purified antigenic proteins produced from the cloned viral genes
      in a variety of vector/host expression systems, (ii) chemical synthesis or the
      use of fusion vectors to produce peptides corresponding to known epitopes, (iii)
      defined attenuations, i.e. specific genetic alterations, of live virus vaccines,
      (iv) the use of live bacterial or viral vectors to deliver resistance genes or
      viral antigens, (v) anti-idiotype antibodies, and (vi) DNA vaccines where
      purified plasmid DNA expressing the pathogen gene under a eucaryotic promoter is
      injected. All of these technologies have been used more or less successfully in
      the development of vaccines for aquacultured species. However, the requirements
      for safety, effectiveness, ease of application and low cost/dose restrict their
      commercial development for aquaculture. The ideal viral vaccine for aquaculture
      must be effective in preventing death, be inexpensive to produce and license,
      provide immunity of long duration, and be easily administered. In addition, these
      vaccines must not only provide protection against the lethal effects of virus
      infection but prevent the formation of virus persistence. This is especially true
      for infectious haematopoietic necrosis virus (IHNV) which has been shown to
      persist in survivors in the presence of high antibody levels. Since resolution of
      virus persistence is thought to be correlate with cell-mediated immunity,
      vaccines designed to augment the cell-mediated immunity must be developed for
      fish. Approaches that are being considered include the use of cytokines in
      combination with subunit vaccines and the use of specific MHC-I inducer adjuvants
      with the vaccine. The "tailoring" of vaccine immunogenicity using different
      combinations of antigen and adjuvant will be presented.

PMID- 9270857
TI  - In vitro methods for vaccine evaluation.
AB  - This paper reviews aspects related to the establishment of in vitro assays for
      fish vaccine evaluation and presents mainly assays for potency testing where
      specific immune responses are monitored. Aspects related to the evaluation of
      currently available bacterial vaccines are focused on, and results are mainly
      presented where both immune responses and protection are assessed in the same
      trial. Although there is no agreement on which antigens are protective in such
      vaccines, results show that there are candidate antigens from the various
      pathogens that are strongly immunogenic in fish, and a correlation between the
      immune responses they elicit and protection is striking. For some antigens, a
      clear relationship between immunizing dose, antibody response and protection is
      evident, which is an important basis for a potency test. Results presented on the
      evaluation of live vaccines show that assays to measure specific T-cell responses
      are required. These assays, like lymphocyte proliferation and detection of
      macrophage activation factor, are considered to be less specific than antibody
      assays and are hampered by greater variations between individual responses.
      However, when reagents become available for the assessment of cytokine release in
      an ELISA based assay, this will allow easier assessment of cellular immune
      responses in fish and could form the basis for potency testing of vaccines where
      protection is correlated with cellular immunity.

PMID- 9270858
TI  - Strengths and weaknesses of different challenge methods.
AB  - The development of effective fish vaccines is greatly dependent on reproducible
      standardised challenge methods. Different test protocols involving bath exposure,
      intra-peritoneal and intra-muscular injection and co-habitation are all well
      described in the literature. Ideally, to represent the many facets of infectious
      diseases in fish, a test challenge method should closely mimic natural exposure
      to the pathogen and ensure that immune mechanisms located in the body surfaces
      play their role. Bath and co-habitation challenges best fulfil this requirement.
      On the other hand, these methods are more difficult to control and standardise
      than injection methods. The pathogenicity of some strains of bacteria may also be
      insufficient to induce a satisfactory outbreak of disease in the target species
      when using bath or co-habitation challenge. A common measure of efficacy of a
      vaccine is by Relative Percent Survival (RPS), which expresses the proportional
      relationship between mortalities in a vaccinated group compared to unvaccinated
      controls. It has been demonstrated that RPS may vary significantly between
      challenge methods in groups of Atlantic salmon vaccinated with the same batch of
      vaccine. Also, RPS may vary for the same batch of vaccine when used in identical
      test systems at different times. Great care should therefore be taken when
      competitive products evaluated in different tests are compared. As several
      vaccines have been marketed and shown to have very good efficacy under field
      conditions, such products could be introduced as reference standards when testing
      new candidates for marketing authorisation.

PMID- 9270859
TI  - Statistical aspects of fish vaccination trials.
AB  - Vaccine trials are performed to measure the efficacy of vaccines or vaccination
      strategies. The statistical aspects pertain both to design and analysis of such
      trials. In experimental trials, the design should ensure that the groups to be
      compared are equal in all respects except for the factor to be assessed. This is
      achieved by proper randomisation procedures. The diagnosis of cases should as far
      as possible be carried out without knowledge of vaccination status (blinding). If
      the administration of a vaccine per se is considered to influence the outcome, a
      similar administration of placebo in the control group should be considered. The
      required sample size will depend on a specified significance level, a specified
      power, and on the magnitude of the effect one wants to detect. If the cumulative
      numbers of cases in vaccinated and unvaccinated groups are registered at the end
      of the observation period, the effect can be measured by the risk ratio, risk
      difference or the relative percent survival. If the estimation is based on a fish
      time approach and the presumption of constant rate of outcome over time is
      fulfilled, the rate ratio or the rate difference can be estimated. If the rate is
      not constant, the life table would be a method of choice. In the statistical
      analysis of the vaccination effect it is important to consider the assumptions on
      which the statistical tests are based. Proper choice of the experimental and
      statistical units in the trials is crucial. If a trial is set up with the
      individual fish as the statistical unit, adjusting for dependence (cluster
      effect) between the units may be indicated. If possible, the vaccine effect
      should be given by the point estimate and the confidence intervals. The
      statistical aspects of fish vaccination trials are based on general principles
      for controlled clinical trials, but they are also influenced by characteristics
      connected to the fish population and the experimental conditions.

PMID- 9270860
TI  - The pitfalls of field trials in fish vaccinology.
AB  - Field trials are essential for accurately assessing the worth of a vaccine under
      actual conditions of use. Compared with the laboratory, the dynamics of the host,
      pathogen, and environment in a production setting can produce both subtle and
      dramatic differences on the performance of the vaccine and the immune response.
      Because of this, field trials are conducted by manufacturers in vaccine
      development and are required by many national regulatory agencies to evaluate
      safety and/or efficacy before granting vaccine licenses. Aquaculture producers,
      veterinarians and fish health professionals can use field trials to analyse the
      cost-benefit of a vaccination programme for a facility, or to compare competitive
      products. Vaccine field trials are more than merely using the products in the
      field. Small efficacy effects can result in considerable cost reductions to the
      fish farmer. Proper field trial design, conduct and analysis is critical to
      detecting these effects. However, field trials are also fraught with many
      pitfalls that can result in failure or misleading conclusions. The discussion
      regarding possible pitfalls of vaccine field trials in aquaculture is divided
      into two parts: 1) the art and 2) the science of successful field trials. The art
      of successful field trials involves dealing with the "people" aspect which is
      necessary for initial and continuing compliance. Meticulous planning is
      essential, including a written protocol to which everyone agrees by signature.
      The bottom line to the art of field trials is anticipation and discussion of all
      possible eventualities together with constant communication with the farmer and
      site supervisor. The science of successful fields trials involves anticipating
      and realizing the logistical and statistical difficulties in design and
      implementation. Problems often encountered are: lack of stated quantifiable
      purpose; low power of the test due to inherent small sample size, large variation
      and small margin of effect; lack of estimate for anticipated results in controls
      and unpredictable challenges; non-blinding design with bias and unequal
      treatment; one or few measures of outcome; lack of redundancy in sites selected;
      poor statistical design and analysis with violation of assumptions; herd effects;
      inability to assess long-term effects through several production cycles; and
      manufacturer/producer expense.

PMID- 9270861
TI  - Regulation of veterinary biological products for fish in the United States.
AB  - The USDA regulates veterinary biological products for fish in the U.S. to ensure
      that they are pure, safe, potent and efficacious, and not worthless,
      contaminated, dangerous, or harmful. To market a biological, USDA establishment
      and product licences (for U.S. biologicals manufacturers) or a USDA permit (for
      U.S. representatives of biologicals manufacturers abroad) are required. The USDA
      will issue the appropriate licences or permit following submission of acceptable
      documentation by the applicant, inspection of production facilities and
      confirmatory testing by the USDA.

PMID- 9270862
TI  - European regulations relevant to the marketing and use of fish vaccines.
AB  - In the Member States of the European Union (EU), vaccines cannot be marketed
      unless a marketing authorisation has been granted for the product by the relevant
      competent authority, and there are similar requirements in other European
      countries, such as Norway. The legal basis of this control in EU Member States is
      through the national implementation of the various directives and regulations,
      principally Council Directive 81/851/EEC as amended and Council Regulation (EEC)
      2309/93. This Regulation also provides the framework for the decentralised system
      for authorisation of products in more than one member state and for the
      centralised procedure for authorisation in all of the countries of the EU.
      Council Directive 81/852/EEC as amended and EU guidance notes set out
      requirements for the quality, safety and efficacy of the vaccines. Only products
      which conform with the requirements can now be given an authorisation for
      marketing in a Member State, and all existing vaccines must be shown to conform
      by April 1998. Requirements for vaccines are also included in the monographs of
      the European Pharmacopoeia, which set legally binding standards for products on
      the market in Europe. Monographs for various types of fish vaccines are now being
      elaborated. In addition to control through marketing authorisations, a number of
      European countries have a system for official control of each batch which is to
      be released for sale. Distribution and supply of the products are also subject to
      controls. The system used varies from country to country but, for example, in
      some countries vaccines can only be supplied on receipt of a prescription from a
      veterinary surgeon. Thus, the marketing and use of fish vaccines are subject to a
      series of regulations which must be addressed by any company wishing to supply
      such products in Europe.

PMID- 9270863
TI  - Canadian regulatory requirements for recombinant fish vaccines.
AB  - In Canada, veterinary biological products derived by using conventional and new
      techniques of biotechnology are licensed and regulated under the Health of
      Animals Act and Regulations. Biological products include vaccines, bacterins,
      bacterin-toxoids and diagnostic kits which are used for the prevention, treatment
      or diagnosis of infectious diseases in all species of animals, including fish.
      Veterinary biologicals are licensed on the basis of fulfillment of four criteria:
      purity, potency, safety and efficacy. A risk-based approach is used to evaluate
      the safety of the product in target species, as well as non-target species,
      humans and the environment. On the basis of biological characteristics,
      biotechnology derived veterinary biologicals have been divided into two broad
      categories, high and low risk products. The paper describes the regulatory
      framework for the licensing of veterinary biologicals in Canada, with emphasis on
      the regulatory considerations for recombinant fish vaccines. Stages of movement
      of the product from research in a contained laboratory facility to a fully
      licensed product for free sale are discussed. The requirements for field testing
      and environmental assessment involved in these stages are highlighted.
      Manufacturers and researchers who intend to commercialize experimental vaccines
      are encouraged to consult with the Veterinary Biologics and Biotechnology Section
      early in the product development process so that the research data and quality
      assurance documentation are consistent with regulatory requirements.

PMID- 9270864
TI  - Regulatory harmonization--a vaccine industry perspective.
AB  - With growth and diversification of aquaculture has come the dissemination of
      diseases and the increased need to use control measures, both preventative and
      therapeutic. Preventative measures include good husbandry practices, adequate
      nutrition and the use of vaccines. Vaccines for aquaculture have generally fallen
      under the regulatory control of national veterinary medicinal or biological
      agencies and with that a diverse range of regulatory requirements for
      authorization and use. More so than any other food animal industry, aquaculture
      is an international industry with individual entities holding multinational
      ownership. This situation has created unique problems for the manufacturers of
      biologicals attempting to service the industry. In recent years, a concerted
      effort has been made to harmonize regulations to facilitate international trade
      of vaccines as well as vaccinated animal stocks and their processed food products
      within and among trading partners. Standardization of requirements for
      manufacture and testing would ensure national and international interests and
      consumers of pure, safe and effective products. As the path to harmonization has
      been slow and not without disagreements, the question remains: What will the
      standardized requirements be? The manufacturing philosophies of process control
      (Good Manufacturing Practice) and governmental final product testing for batch
      release can create a duplicity of effort on the part of the manufacturer that
      equates to higher economic costs and greater time constraints. The current lack
      of standardized quality control test methods often means conducting multiple
      tests to provide the same result. Although efforts are being made to recognize
      these differences, historical regulations today are based on injectable vaccines
      for warm-blooded animals. Administration of vaccine products to cold-blooded
      aquatic species by immersion, bath and oral routes, as well as by injection,
      creates interpretive problems for manufacturers and regulators alike. Industry
      encourages and awaits regulatory harmonization, standardization or equivalence.
      It also offers and would appreciate an active role in the final process.

PMID- 9270865
TI  - Reduction of antibacterial drug use in Norwegian fish farming due to vaccination.
AB  - Sales statistics for antibacterial drugs and vaccines intended for use in farmed
      salmonids in Norway were collected and analysed. In 1993, there was a substantial
      reduction in annual sales figures for antibacterial drugs, which continued in
      1994 and 1995. Oil-adjuvanted vaccines containing antigens against furunculosis
      were introduced in the fall of 1992. Introduction of oil-adjuvanted vaccines has
      been the single most important cause for the substantial reduction in use of
      antibacterial drugs in Norwegian fish farming industry.

PMID- 9270866
TI  - Vaccinated fish welfare: protection versus side-effects.
AB  - Active immunisation of fish involves a number of potentially harmful procedures
      like handling, anaesthesia or injection of more or less toxic substances.
      Adjuvanted vaccines may cause inflammation, granuloma and pigmentation at the
      site of injection. Intraperitoneal administration of oil-adjuvanted vaccines to
      Atlantic salmon pre-smolts has occasionally resulted in impaired growth and
      reduced carcass quality. The consequences of such vaccination for fish welfare
      may therefore be questioned. With respect to furunculosis caused by Aeromonas
      salmonicida, scientific data suggest, however, that only oil-adjuvanted vaccines
      are protective throughout the production cycle of farmed salmon. Data are
      presented to show that salmonids are highly at risk to epizootics if left
      unprotected against this or other endemic diseases. A panel of parameters partly
      adopted from experimental animal medicine is proposed to assess the impact of
      vaccine side-effects in farmed fish. In intensive salmon aquaculture systems,
      reduced disease risks are thought to justify the observed level of side-effects
      following current vaccination practices. For future fish vaccines, reduction of
      side-effects without compromising long-term protective immunity constitutes a
      challenging goal.

PMID- 9270867
TI  - Operator safety during injection vaccination of fish.
AB  - Reports of adverse health effects to vaccinators after self-injection of fish
      vaccine motivated the present study which aimed at identifying risk factors and
      improving risk management. Information was collected through interviews with
      members of professional vaccinator teams, and with physicians who had treated
      injured vaccinators. In addition, a questionnaire was distributed among salmon
      farmers. Professional vaccinators reported from one to more than 50 stabs or self
      injections during the vaccination season. Two cases of hospitalization due to
      anaphylactic reactions are described. Self-injections occurred exclusively on
      fingers and hands. The clinical picture is classified into four categories
      according to the type and severity of the reaction. The overall risk of self
      injection leading to serious health effects was low, although the data do not
      allow a precise estimate. The collected information suggests that allergic
      hypersensitivity reactions occurred in two vaccinators, whereas increasing
      tolerance was reported from others. No information indicating infectious
      reactions was obtained, suggesting that non-steroid anti-inflammatory drugs
      constitutes an appropriate therapy for self-injection events. The use of a safety
      bow attached to the syringe and improved training and awareness of personnel
      apparently have reduced the incidence of self-injection since this study was
      conducted. Health risks for vaccinators have further been reduced by equipping
      vaccinators with adrenaline and the improved knowledge of local doctors regarding
      recommended treatment.

PMID- 9270869
TI  - Vaccination strategies in seawater cage culture of salmonids.
AB  - Successful vaccination depends both on the development of protective vaccines and
      their correct use. In addition to deciding which diseases to vaccinate against,
      the choice of the method, timing, and use of revaccination must be considered. In
      seawater culture of salmonids, vibriosis and furunculosis are the most important
      diseases against which to vaccinate in many parts of the world, while cold-water
      vibriosis is of great significance in Atlantic salmon in some areas with low
      water temperatures. A vaccine against infectious pancreatic necrosis (IPN) has
      also been introduced recently. For optimal protection of salmonids in sea-water,
      vaccination should be carried out some time before sea transfer, in order to give
      immunity sufficient time to develop, and to avoid handling stress during
      smoltification. On the other hand however, vaccination should not be carried out
      too early, as the degree of immunity declines with time. Water temperature is an
      important factor when deciding when to vaccinate. Recent research has
      demonstrated that Atlantic salmon may be vaccinated successfully at low water
      temperatures. In general, vaccination by the injection method gives superior
      protection. Vaccines against the Vibrio-infections can also be administered
      successfully by immersion. However, due to lower levels of immunity, the need for
      a booster vaccination is greater when such a method is used. As regards vaccines
      against furunculosis, adjuvants are needed in order to achieve good protection,
      and, consequently, administration by injection is the only option.

PMID- 9270868
TI  - Vaccination strategies in freshwater salmonid aquaculture.
AB  - The focus of this chapter is antibacterial vaccines. The main salmonid species in
      freshwater aquaculture is the rainbow trout. Other salmonid species are produced
      on a limited scale. The most important bacterial fish diseases in European
      freshwater aquaculture are the rainbow trout fry syndrome-RTFS-(Flavobacterium
      psychrophilum) and enteric redmouth disease-ERM-(Yersinia ruckeri) which are
      widespread and cause serious epizootics, while furunculosis (Aeromonas
      salmonicida) is endemic, only giving overt disease under extremely stressing
      conditions. In the hatchery, there is a need for vaccination against RTFS (not
      commercially available) and ERM; in the ponds it is urgent to vaccinate against
      ERM, while the importance of furunculosis vaccination is not clear. The fish for
      ongrowing in saltwater should be vaccinated against ERM, furunculosis and
      vibriosis. Commercial vaccines are available against these diseases, either as
      single component or combination vaccines for immersion and injection-and oral
      vaccines are under registration. Hitherto, there has not been much strategic
      research on vaccination in freshwater; however recent results suggest that with
      the regime of vaccines available (and soon available), fish should be vaccinated
      with an ERM immersion vaccine in the hatchery approximately four weeks before
      transfer to the ponds. To cover the growth period in fresh water an oral booster
      should be given two to three months later. There is a need for development and
      research in strategic use of an RTFS and a furunculosis vaccine in freshwater
      aquaculture.

PMID- 9270870
TI  - Glucan-induced disease resistance in tiger shrimp (Penaeus monodon).
AB  - Non-specific disease resistance induced by yeast cell wall extract, beta-1,3-1,6
      glucan, was demonstrated in the tiger shrimp. In this study beta-1,3-1,6-glucan
      was administered to shrimps by immersion before culturing and orally during the
      culturing period. Challenge of the treated shrimps with the virulent pathogens,
      Vibrio vulnificus and viral agents extracted from the white spot syndrome
      victims, yielded promising results. The tolerance of glucan-treated shrimps was
      slightly enhanced to stresses including catching, transport and ammonia. The
      growth and survival rates of treated and untreated shrimps were not significantly
      different. Therefore, we suggest that beta-1,3-1,6-glucan can be used as an
      immuno-stimulant of cultured shrimps and may benefit shrimp farmers.

PMID- 9270871
TI  - Protein phosphorylation sites regulate the function of the bipartite NLS of
      nucleolin.
AB  - Nucleolin is a major component of the nucleolus. In Xenopus laevis, a maternal
      store of nucleolin is accumulated in the multiple nucleoli generated during
      oogenesis. This maternal nucleolin is distributed throughout the cytoplasm of the
      egg during oocyte maturation and after fertilization it is gradually
      reaccumulated in the nuclei of the embryo. Cytoplasmic localization of nucleolin
      coincides with massive phosphorylation by p34cdc2 kinase, and nuclear
      translocation is accompanied by net dephosphorylation. Multiple phosphorylation
      consensus sites for the cell cycle-dependent p34cdc2 kinase and for protein
      kinase CK2 are clustered in the N-terminal domain of nucleolin. To assess the
      efficiency of the bipartite nuclear localization signal, we have constructed
      fusion proteins consisting of maltose binding protein (MBP) and the nuclear
      localization signal of nucleolin. In addition, either an acidic domain of
      nucleolin without phosphorylation sites, or an acidic domain containing 4 CK2
      sites, or a cluster of 5 cdc2 sites was fused to the MBP-nuclear localization
      signal (MBP-NLS). Nuclear translocation of these constructs was tested in an in
      vitro system consisting of Xenopus egg extract and sperm nuclei. Nuclear
      targetting of MBP by the bipartite nuclear localization signal of nucleolin
      became significantly more efficient after addition of either CK2 sites or cdc2
      sites to the MBP-NLS construct. Yet the cdc2 sites play a dual role. They enhance
      nuclear translocation exclusively in their dephosphorylated state and promote
      cytoplasmic localization when phosphorylated, thereby providing a powerful cell
      cycle-dependent regulatory element of the nuclear localization signal.

PMID- 9270873
TI  - Ortho-vanadate affects both the tyrosination/detyrosination state of spindle
      microtubules and the organization of XTH-2 spindles.
AB  - Mitotic spindles of a cultured endothelial cell line from Xenopus tadpole heart
      (XTH-2) contain distinct subsets of differentially stabilized microtubules (MTs)
      enriched in tyrosinated (Tyr) and in nontyrosinated (Glu) tubulin. Generally, the
      distribution of the more labile Tyr-MTs and of the Glu-MTs indicative for the
      more stable MT-subclass was remarkably different. During all mitotic stages the
      Tyr-staining of spindle fibers predominates, whereas the Glu-species was mainly
      restricted to the peripheral regions of half spindles where the MTs have to
      sustain a bending stress. Moreover, Glu-tubulin is enriched in prophase
      centrosomal areas, and, from metaphase on, exclusively also in the centrioles.
      Glu-positivity does not remain constant, instead, the intensity weakens from
      metaphase to telophase reflecting the decreasing MT nucleating capacity of the
      centrosomes. During the spindle cycle, the interzonal spindle at the anaphase
      telophase transition exceeds all other stages in Glu-stainability and retains the
      high amount of detyrosinated MTs during telophase. External application of
      millimolar vanadate has different effects upon spindle components organization:
      First, additional assembly of Tyr-MTs together with a Glu-negative reaction of
      the centrioles was registered and, secondly, a drastic disarrangement of the Tyr
      staining spindle fiber component became evident. At the onset of anaphase, an
      extreme spindle lengthening presumably due to the separation of the Tyr- and Glu
      MTs occurred. Obviously, the Glu-spindle fibers were less affected and remained
      largely in their original spindle position. Redistribution of anti-dynein
      staining following vanadate incubation suggests a causal relationship between
      inhibition of dynein motor proteins and disarrangement of different microtubular
      spindle components. These results suggest that the changes in the spindle
      framework are at least partly due to malregulation of centrosomal phosphorylation
      events, respectively to inactivation of special cross-bridging proteins
      interacting between distinct MT-subsets by a phosphate mimicking effect of
      vanadate and finally, by a vanadate-induced displacement of polar asters.

PMID- 9270872
TI  - Echistatin induces decrease of pp125FAK phosphorylation, disassembly of actin
      cytoskeleton and focal adhesions, and detachment of fibronectin-adherent melanoma
      cells.
AB  - B16-BL6 mouse melanoma cells cultured on fibronectin-coated dishes were detached
      by treatment with echistatin, an RGD-containing disintegrin. Echistatin was
      active at micromolar concentrations and was not cytotoxic. Its effect was dose
      dependent and reversible. Sequential morphological changes leading to rounding up
      of the cells were detected by phase-contrast microscopy and by immunofluorescence
      analysis. A dramatic reduction in the number and size of focal adhesions and loss
      of cytoplasmic actin filaments were observed well before cell detachment
      occurred. Echistatin treatment down-regulated the phosphorylation of pp125FAK in
      fibronectin-adherent cells in a dose- and time-dependent fashion. The reduction
      of pp125FAK phosphorylation preceded cell detachment and occurred even in the
      presence of orthovanadate, an inhibitor of protein tyrosine phosphatases. These
      results suggest that echistatin detaches cells from the fibronectin substratum by
      inducing a decrease of pp125FAK phosphorylation and that echistatin acts by
      inhibiting protein tyrosine kinase activity rather than activating protein
      tyrosine phosphatases.

PMID- 9270874
TI  - Role of the C-termini of human and chicken plasma retinol-binding proteins.
AB  - The most prominent differences between mammalian and non-mammalian vertebrate
      retinol-binding proteins (RBP) are in the C-terminal sequences. We have cloned
      and sequenced the cDNA for chicken RBP. Transfected COS cells that transiently
      expressed mammalian (human) or non-mammalian (chicken) RBP were used to
      demonstrate that both proteins were able to bind retinol and human transthyretin.
      However, we observed an increased retinol-independent secretion in cells
      expressing chicken RBP and reduced ligand-dependent secretion compared to the
      human protein. It can therefore be concluded that the C-terminal amino acid tail
      which is missing in chicken RBP compared to human RBP might play a role in
      retention and ligand-induced secretion.

PMID- 9270875
TI  - Cellular and subcellular localization along the digestive and pulmonary tracts of
      a rabbit intestinal mucin differing from MUC2 and containing a 150 kDa light
      chain.
AB  - Two immunologically different rabbit intestinal mucins were separated by
      performing fractionated ammonium sulfate precipitation, dialysis against pH 5.5
      buffer and filtration through a Sepharose CL 2B column. They each contain a light
      chain with apparent molecular masses of 150 and 140 kDa, respectively. These L
      chains were purified after reduction and carboxymethylation of the disulfide
      bridges of the native mucins, and their first 22 amino acid sequence was
      determined. The sequence of the 140 kDa chain is 100% and 95% identical to the N
      terminal sequence of the L-chains from human and rat MUC2, respectively and only
      54% identical to the sequence of the 150 kDa chain. It can be concluded that the
      rabbit counterpart of MUC2 exists and that another rabbit intestinal mucin, named
      here M-6G2, contains an L-chain. As in the case of MUC2, the M-6G2 L-chain may
      have resulted from a limited proteolysis. This proteolysis seems to occur in a
      region which is conserved in both mucins, since the two chains both have
      approximately the same length and the same five-amino acid N-terminal sequence.
      The cellular expression of M-6G2 along the digestive and respiratory tracts
      differs from that of the other mucins known so far to be present in the human
      small intestine.

PMID- 9270876
TI  - Perlecan is responsible for thrombospondin 1 binding on the cell surface of
      cultured porcine endothelial cells.
AB  - Thrombospondin 1 (TSP1), a high molecular weight glycoprotein of the
      extracellular matrix, interacts with glycosaminoglycan at the cell surface of
      porcine endothelial cells (Schon et al., Eur.J. Cell Biol. 59, 329-339 (1992)).
      In this study we identified and characterized the heparan sulfate proteoglycan
      (HSPG) responsible for TSP1 binding and uptake in endothelial cells and
      investigated some properties of the TSP1-proteoglycan interaction. Porcine
      endothelial cells synthesize proteoglycans containing heparan sulfate (HS) or
      chondroitin/dermatan sulfate (CS/DS). CS/DS-containing compounds are present
      predominantly in the culture medium. On Sepharose CL-4B the cellular proteoglycan
      fraction yielded two HS-containing compounds with a Kav = 0.18 and Kav = 0.55.
      Only the larger HS-containing component was sensitive to alkaline treatment and
      was also found in the medium fraction. Trypsin treatment of endothelial cells
      revealed that the large HS-containing component represents a cell surface
      associated proteoglycan, whereas the smaller fraction represents a pool of
      intracellular HS-chains. The cellular HSPG is partially localized at the apical
      cell surface but also incorporated and tightly bound to the subendothelial
      matrix. Deglycosylation of the high molecular weight HSPG resulted in the
      identification of a core protein of about 400 kDa. Using specific antibodies, in
      ELISA assays and in immunoblot analysis we observed that the large HSPG is
      identical to the extracellular matrix proteoglycan, perlecan. Immunohistochemical
      studies confirmed the location of perlecan on the apical cell surface and
      additionally as a dense fibrillar network surrounding the cells. Purified
      perlecan bound to TSP1 in a dose-dependent manner and the binding was mediated by
      its glycosaminoglycan side chains. In competition assays using various sulfated
      polysaccharides, heparin potently inhibited binding of perlecan to TSP1
      immobilized on nitrocellulose. Dermatan sulfate was a less effective inhibitor.
      Calcium bound to TSP1 was found to influence its capacity for binding perlecan.
      The present data provide evidence that perlecan is required for binding and
      concentrating TSP1 at the apical surface of vascular endothelial cells during
      receptor-mediated endocytosis.

PMID- 9270877
TI  - Tumor-associated cysteine proteinase activities in human melanoma cells and
      fibroblasts of different origin.
AB  - Specific catalytic activities of cysteine proteinases including cathepsins B (EC
      3.4.22.1) and L (EC 3.4.22.15) in human melanoma cell lines SK-MEL-28, SK-MEL-30,
      MEL-HO and in fibroblasts of different origin are reported. Cell line-specific pH
      profiles of these cysteine proteinases were determined fluorometrically with
      benzyloxycarbonyl-phenylalanyl-arginine-amidomethylcoumarine (Z-Phe-Arg-AMC)
      under saturated conditions. Single activities of cathepsins B and L were
      inactivated by urea and by benzyloxycarbonyl-phenylalanyl-phenylalanine
      diazomethylketone (Z-Phe-Phe-CHN2) in order to describe the activities of these
      enzymes separately. The melanoma cell line MEL-HO, which originated from a
      primary lesion, showed highest activity of an unknown cysteine proteinase. This
      enzyme is not inactivated by urea and Z-Phe-Phe-CHN2 and has a Michaelis constant
      (K(M) value) of approximately 1 mM. The specific characteristics suggest that it
      is a tumor-associated cathepsin B. In addition, high invasive subpopulations of
      SK-MEL-28 and SK-MEL-30 cell lines isolated by an invasion assay showed higher
      proteinase activities than the low invasive subpopulations. Furthermore, in
      fibroblasts originating from melanoma tissue cysteine proteinase activities were
      increased compared to normal skin fibroblasts. In conclusion, these results
      indicate that these cysteine proteinases shown here are tumor-associated
      proteinases, possibly facilitating invasion and dissemination of melanoma cells.

PMID- 9270879
TI  - Intracellular distribution of phospholipase C gamma 1 in cell lines with
      different levels of transformation.
AB  - The intracellular localization of phospholipase C gamma 1 (PLC gamma 1) was
      studied in cell lines with different levels of cell transformation.
      Immunofluorescence analysis of cell lines with differently organized actin
      cytoskeletons (A431 cells, HeLa cells, mouse hepatoma MH 22A, Zajdela ascitic
      hepatoma, primary human embryo skin and lung fibroblasts) gave evidence that PLC
      gamma 1 is colocalized only with cortical actin and not with stress fibers.
      Coimmunoprecipitation experiments indicated that PLC gamma 1 was bound to actin
      in all cell lines investigated. Further, the nuclei of highly transformed cell
      lines (A431 cells, HeLa cells, mouse hepatoma MH 22A, rat Zajdela ascitic
      hepatoma) were labeled with the anti-PLC gamma 1 antibody. In contrast, PLC gamma
      1 was not observed in the nuclei of primary human embryo skin or lung
      fibroblasts. Since PLC gamma 1 exists only in the nuclei of highly transformed
      cell lines, we propose that the distinctive intracellular localization of PLC
      gamma 1 in normal and highly transformed cell lines may reflect differences in
      cell signaling systems and mitogenic cell signal transduction.

PMID- 9270878
TI  - Newly identified Chinese hamster ovary cell mutants defective in peroxisome
      biogenesis represent two novel complementation groups in mammals.
AB  - We isolated peroxisome biogenesis mutants from Chinese hamster ovary (CHO) cells,
      using the 9-(1'-pyrene)nonanol/ultraviolet (P9OH/ UV) method and wild-type CHO-K1
      cells that had been stably transfected with cDNA encoding Pex2p (formerly
      peroxisome assembly factor-1, PAF-1). Three mutant cell clones, ZP110, ZP111, and
      ZP114, showed cytosolic localization of catalase, thereby indicating a defect in
      peroxisome biogenesis, whereas ZP112 and ZP113 contained fewer but larger
      catalase-positive particles. Mutant ZP115 displayed an aberrant, tubular
      structure immunoreactive to anti-catalase antibody. Mutants lacking
      morphologically recognizable peroxisomes also showed the typical peroxisome
      assembly-defective phenotype such as severe loss of catalase latency and
      resistance to 12-(1'-pyrene)dodecanoic acid (P12)/UV treatment. ZP110 and ZP111,
      and ZP114 were found to belong to two novel complementation groups, respectively,
      by complementation group analysis with cDNA transfection and cell fusion. Cell
      fusion with fibroblasts from patients with peroxisome biogenesis disorders such
      as Zellweger syndrome revealed that ZP110 and ZP114 could not be classified to
      any of human complementation groups. Thus, ZP110/ZP111 and ZP114 are the first,
      two peroxisome-deficient cell mutants of newly identified complementation groups
      distinct from the ten mammalian groups previously characterized.

PMID- 9270880
TI  - Characterization of MEC 14.7, a new monoclonal antibody recognizing mouse CD34: a
      useful reage for identifying and characterizing blood vessels and hematopoietic
      precursors.
AB  - Endothelial cell-specific molecules are potential targets for new therapeutic
      strategies in the control of inflammatory reactions, immune responses and
      neoangiogenesis. We describe the production and characterization of MEC 14.7, a
      monoclonal antibody directed to murine endothelial cells recognizing a
      glycosylated protein with an apparent molecular mass of about 100 kDa in cultured
      endothelioma cell lysate and about 80 kDa in lung lysate. MEC 14.7 antigen was
      selectively expressed by the endothelium in vivo, particularly in small vessels
      and neoformed capillaries and by developing vascular structures in embryonal
      bodies. Deglycosylation of the molecule with neuraminidase, O- and N-glycanase
      showed that the MEC 14.7 epitope is neuraminidase-sensitive. MEC 14.7 antigen was
      purified from lung lysates by chromatographic techniques, and sequenced internal
      peptides indicated it was identical with murine CD34. Thus the apparent molecular
      mass of CD34 is heterogeneous, depending on the glycosylation state in the
      different cell types. Immunomagnetic isolation and culture of MEC 14.7-positive
      bone marrow cells showed that this antibody recognizes hematopoietic progenitors
      (particularly myelomonocytic) and can be used in murine models of bone marrow
      reconstitution.

PMID- 9270881
TI  - Analytical electron microscopy as a powerful tool in plant cell biology: examples
      using electron energy loss spectroscopy and X-ray microanalysis.
AB  - Energy filtering transmission electron microscopy in combination with energy
      dispersive X-ray analysis (EDX) and quantumchemical calculations opens new
      possibilities for elemental and bone analysis at the ultrastructural level. The
      possibilities and limitations of these methods, applied to botanical samples, are
      discussed and some examples are given. Ca-oxalate crystals in plant cell vacuoles
      show a specific C K-edge in the electron energy loss spectrum (EELS), which
      allows a more reliable identification than light microscopical or cytochemical
      methods. In some dicots crystalline inclusions can be observed in different cell
      compartments, which are identified as silicon dioxide or calcium silicate by the
      fine structure of the Si L2,3-edge. Their formation is discussed on the basis of
      EEL-spectra and quantumchemical calculations. Examples concerning heavy metal
      detoxification are given for some tolerant plants. In Minuartia Zn is bound as Zn
      silicate in cell walls; Armeria accumulates Cu in leaf idioblasts by chelation
      with phenolic compounds and Cd is precipitated as CdS/phytochelatin-complexes in
      tomato.

PMID- 9270882
TI  - Pathophysiology and therapy for allergic and nonallergic rhinitis: an updated
      review.
AB  - Symptoms from rhinitis can be assessed to be more troubling to the patient than
      symptoms from asthma. Further, the array of bioactive mediators, cytokines, and
      cells in nasal mucosa suggests that rhinitis is a much more complex condition
      than formerly thought. The presence of allergic rhinitis is a risk factor for
      emergence of asthma. Topical nasal corticosteroids have a relatively flat dose
      response curve and have onset of action within 1 to 2 days for some patients.
      Allergen immunotherapy remains the only immunomodulator for patients with
      allergic rhinitis, with the possible exception of long-term administration of
      nasal corticosteroids.

PMID- 9270883
TI  - Patterns of nasal eosinophilia in allergy clinic patients as determined by swab
      and curette sampling.
AB  - The presence of eosinophils in nasal secretions often characterizes inflammatory
      disease in the nose and paranasal sinuses. This study analyzed differential
      associations between various clinical parameters and the presence of nasal
      eosinophilia in mucosal specimens obtained by two sampling methods (swab and
      curette-probe). Nasal mucosal secretions were obtained in patients attending an
      adult allergy clinic using both sampling methods for each patient. The presence
      of eosinophilia as determined by both methods had significant associations with
      1) nasal mucosal pallor, 2) younger age, and 3) the presence of basophilic cells.
      To examine diagnostic characteristics of the two sampling methods of determining
      eosinophilia as a characteristic of allergic rhinitis, receiver operating
      characteristic (ROC) curves were evaluated for patients categorized as having
      allergic rhinitis on the basis of elevated aero-allergen specific IgE, and
      rhinitis based on either a) significant nasal mucosal appearance abnormalities,
      or b) a referring physician's diagnosis of rhinitis. The curette-probe determined
      nasal eosinophil quantitations had greater areas under the ROC curves when
      rhinitis was defined on the basis of mucosal appearance. On the other hand, the
      swab determined eosinophil quantitations had greater ROC curve areas when
      rhinitis was defined on the basis of referring diagnosis. In summary, nasal
      eosinophilia determined by curette or swab sampling has differences in strengths
      of their clinical associations.

PMID- 9270884
TI  - An update on the immunopathogenesis of asthma as an inflammatory disease enhanced
      by environmental pollutants.
AB  - The pathogenesis of asthma now centers on the role of bronchial mucosal
      inflammation of mixed cellularity in addition to the characteristic airways
      hyperresponsiveness and reversible obstruction. Mast cell mediators play an early
      role in the asthmatic airway response but through induced arachidonic acid
      metabolites and cytokine production may also participate in the late phase
      response. A unique feature of the late phase response is the abundant
      accumulation of eosinophils in the bronchial respiratory mucosa that is enabled
      by profound effects of the Th2 cytokine, IL-5. Additionally, the IL-4 gene
      cluster that is responsible for the levels of total serum IgE production has now
      been linked to asthma. With this new insight into the inflammatory mechanisms
      causing asthma, a mounting body of evidence exists to explain the recent
      increases in allergic disease prevalence resulting from environmental pollution.
      Air pollution, including the contribution by diesel exhaust particle emissions,
      has been shown to enhance both nasal IgE production and the gene expression of
      Th2 cytokines. It is believed that diesel particulates act as adjuvants in the
      immune system that promote the development of allergic inflammation.

PMID- 9270885
TI  - Review of trimellitic anhydride (TMA) induced respiratory response.
AB  - Acid anhydrides such as trimellitic anhydride (TMA) are of interest due to their
      important industrial uses and to their adverse health effects in exposed
      populations. Important industrial uses of TMA include the production of epoxy and
      alkyd resins used to manufacture a variety of coating materials. The adverse
      health effects are a result of its direct irritant effects on mucosal surfaces in
      all exposed humans as well as its ability to cause immunologic sensitization in a
      small proportion of humans. In those individuals who are immunologically
      sensitized, reexposure to TMA can result in well described immunologic syndromes:
      asthma-rhinitis, late respiratory systemic syndrome (LRSS), and very rarely
      pulmonary disease anemia syndrome (PDA). In summary, adverse health effects of
      TMA are due to its effects as an irritant, an immunologic sensitizer, or a
      combination of both.

PMID- 9270886
TI  - Complement abnormalities with lower extremities discomfort in Vietnamese
      immigrants.
AB  - The objective was to measure complement C'l esterase inhibitor (CIINH) in a group
      of Vietnamese outpatients with lower extremities discomfort of undetermined
      etiology. All 25 female patients were followed between 1992 and 1995. Their age
      ranged from 24 to 82 years old (mean age, 46.68 +/- 13.77). They presented with
      unexplained lower extremities discomfort. They were found to have low levels of
      CIINH (mean, 11.36 +/- 1.44 mg/dL versus control subjects, 15.64 +/- 2.22 mg/dL).
      Twenty-one patients were treated with oral Danazol 200 mg daily for 1-2 months.
      The improvement of the symptoms in our patients coincided with increased CIINH
      level in all of our patients (pretreatment, 11.33 +/- 1.46 mg/dL versus
      posttreatment, 16.82 +/- 2.98 mg/dL with p < 0.001) and the return to normal
      functional activity of CIINH associated with and without Danazol treatment. These
      patients may represent a form of androgen-responsive limited to the lower
      extremity's discomfort associated with low levels of CIINH, normal levels of Clq
      and normal ratio of C4d/C4 that differentiated them from angioedema (hereditary
      or acquired form), having no known precipitating factors or a family history of
      hereditary angioedema.

PMID- 9270887
TI  - Anaphylaxis induced by exercise and related to multiple food intake.
AB  - In some patients, exercise-induced anaphylactic (EIAn) reactions occur only when
      a particular food is eaten before exercise. We describe three patients with EIAn
      induced by different foods. Patients who presented episodes of EIAn performed
      exercise challenges after fasting and 1 hour after a meal without foods suspected
      of predisposing the reaction. Subsequently, patients performed exercises after
      separate intake of each suspected food. Patients underwent skin prick tests (SPT)
      with food extracts. Serum total and specific IgE antibodies to food were
      determined. No reactions were provoked by exercise tests without prior intake of
      suspected foods. Eight of 30 food-exercise combination challenges were positive.
      In Patient 1, tomato, zucchini, and wheat resulted in adverse reactions: in
      Patient 2, potato, peanuts, and tomato; in Patient 3, rice and peanuts. SPTs and
      RASTs to foods predisposing the reaction were positive. Food-exercise combined
      challenge may be useful in identifying foods that favor EIAn in children with
      multiple food-dependent EIAn.

PMID- 9270888
TI  - Food plus exercise plus anaphylaxis: theories and challenge.

PMID- 9270889
TI  - Asthma among the famous. Nathan Tucker (1838-1920), American physician.

PMID- 9270890
TI  - Asthma among the famous. Henry Hyde Salter (1823-1871), British physician.

PMID- 9270891
TI  - Asthma among the famous. Morrill Wyman (1812-1903), American physician.

PMID- 9270892
TI  - Asthma among the famous. Charles Dickens (1812-1870), English author.

PMID- 9270894
TI  - Stretch-sensitive ion channels of neuronal growth cones.
AB  - This paper unifies and outlines some important points made by recent experimental
      work, dealing with MS ion channels and growth cone motility. The considerable
      work carried out in cell biology, neurochemistry and membrane biophysics in the
      past decade allows us to imagine the neurite growth in term of known molecules
      and chains of simple mechanisms. On the other hand, it is becoming increasingly
      clear the real complexity of the growth cone behavior. There remain important
      gaps in our understanding of the role of MS channels in growth cone motility. At
      present, a major limitation for physiological work is the lack of specific
      blockers. An encouraging development of molecular genetic studies of Drosophila
      SAK channels (60) will probably provide valuable tools for straightforward
      experiments.

PMID- 9270893
TI  - The Jewish physician in the post Columbus era: the 15th century Spanish
      inquisition and expulsion revisited in 20th century Germany and Austria.

PMID- 9270895
TI  - Studies on anterograde trophic interactions based on general muscle properties.
AB  - General properties of rat skeletal muscle (extrajunctional membrane and
      contractile properties) are subjected to tight physiological neural regulation,
      as indicated by their striking alterations (up- or down-regulation) following
      denervation. The main contributions of the literature concerning the nature of
      the neural signals which mediate this regulation, are reviewed. The physiological
      regulation of these general properties appears to be operated by the action
      potential activity evoked by motoneurons in the muscle fibres. No need to
      postulate the participation of nerve-borne chemical substances, acetylcholine or
      unidentified "trophic factors", arises from the main experimental evidence. The
      stronger response to denervation of extrajunctional membrane properties with
      respect to pure paralysis is best explained by actions of factors released during
      wallerian degeneration of the transected nerves.

PMID- 9270896
TI  - Motonuclear changes after cranial nerve injury and regeneration.
AB  - Little is known about the mechanisms at play in nerve regeneration after nerve
      injury. Personal studies are reported regarding motonuclear changes after
      regeneration of injured cranial nerves, in particular of the facial and
      oculomotor nerves, as well as the influence that the natural molecule acetyl-L
      carnitine (ALC) has on post-axotomy cranial nerve motoneuron degeneration after
      facial and vagus nerve lesions. Adult and newborn animal models were used.
      Massive motoneuron response after nerve section and reconstruction was observed
      in the motonuclei of all nerves studied. ALC showed to have significant
      neuroprotective effects on the degeneration of axotomized motoneurons. Complex
      quantitative, morphological and somatotopic nuclear changes occurred that sustain
      new hypotheses regarding the capacities of motoneurons to regenerate and the
      possibilities of new neuron proliferation. The particularities of such
      observations are described and discussed.

PMID- 9270897
TI  - Posture and movement: coordination and control.
AB  - Studies are reviewed that address the problem of the variables controlled in the
      maintenance of body posture and generation of limb movement. Vestibulospinal and
      neck reflexes cancel each other in response to roll, but not in response to pitch
      of the animal. In pitch trunk orientation is not effectively stabilized in space.
      Instead, limb length and orientation relative to the vertical are accurately
      controlled in normal cats pitched statically and dynamically by variable angles.
      Control of limb geometry may even take precedence over the control of the
      projected centre of mass. Coordinate transformation results in a constraint of
      planar covariation of the elevation angles at all limb segments in cat posture.
      Because the same constraint applies also to human locomotion, we suggest that
      sharing the same laws of intersegmental coordination for the control of posture
      and locomotion helps to assure the maintenance of dynamic equilibrium during
      movement. Moreover, because several neural sites encode posture and movement in
      gravity-based reference frames, alignment in register of spatial information
      derived from multiple sensors and directed to multiple effectors is made
      possible.

PMID- 9270898
TI  - Classical heart rate conditioning and affective behavior: the role of the
      cerebellar vermis.
AB  - The involvement of the cerebellar vermis in the control of affective behaviors
      and in the coordination of fear-related somatic and autonomic conditioned
      responses is reviewed in this paper. In particular, the review focuses on the
      role of the midline cerebellum (vermis) on the acquisition and/or expression of
      classically conditioned bradycardia in the rabbit. The results of both lesioning
      and electrophysiological experiments indicate that the cortex of lobule III
      through VII is important, although not essential, in the acquisition and
      retention of this response, but it is not the site of its memory trace. The time
      course of the development of the conditioned bradycardia in neonatal rabbits is
      also described. The results obtained are consistent with the possibility that the
      expression of conditioned bradycardia may depend on the complete maturation of
      cerebellum. Moreover, preliminary data on the effects of the ablation of
      cerebellar vermis, performed at early stages of development, on the
      characteristics of conditioned bradycardia showed by adult rabbits are presented.
      These results indicate that cerebellar vermis is essential for the correct
      maturation of the response and that the timing of the lesion is critical for
      determining the characteristics of conditioned bradycardia in the adult.

PMID- 9270899
TI  - Upregulation of Calbindin-D-28k immunoreactivity by excitatory amino acids.
AB  - Excessive or prolonged exposure to excitatory amino acids (EAA) are thought to be
      neurotoxic by altering calcium homeostasis. A protective role of Calbindin-D-28 k
      (Calbindin) has been postulated due to its capacity to buffer calcium. Calbindin
      is highly expressed in the Purkinje cells (PCs), of the cerebellar cortex.
      Changes of the Calbindin immunoreactivity (IR) by the EAA has been here
      investigated in cerebellar slices maintained in vitro. It was found that at low
      temperature, PCs are very slightly immunoreactive and therefore the experiments
      were done at 22 degrees C. The results show that Calbindin-IR increases in PCs
      exposed to the neurotoxic agonists, Kainic acid (KA) and AMPA as well as to
      glutamate (Glu), the endogenous EAA. The increase is very rapid and slowly
      reversible; is induced by excitatory and excitotoxic concentrations of the
      agonists; is independent of the calcium influx. While KA- and AMPA-induced
      Calbindin-IR is blocked by CNQX, the KA/AMPA receptor antagonist, Glu-induced
      Calbindin-IR is only slightly decreased by CNQX and AP5, the NMDA receptor
      antagonist. It is concluded that Calbindin-containing neurons can increase their
      calcium buffering capacity in response to EAA binding to specific receptors, the
      response being independent of, but concomitant to calcium influx.

PMID- 9270900
TI  - Multiple fixed doses of "Seroquel" (quetiapine) in patients with acute
      exacerbation of schizophrenia: a comparison with haloperidol and placebo. The
      Seroquel Trial 13 Study Group.
AB  - Five fixed doses of the atypical antipsychotic "Seroquel" (quetiapine) were
      evaluated to delineate a dose-response relationship, as measured by changes from
      baseline in Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression
      (CGI), and Modified Scale for the Assessment of Negative Symptoms (SANS) summary
      scores, and to compare efficacy and tolerability opposite placebo and
      haloperidol. Three hundred sixty-one patients from 26 North American centers
      entered this double-blind, placebo-controlled trial with acute exacerbation of
      chronic schizophrenia (DSM-III-R). Patients who completed a single-blind, placebo
      washout phase were randomized to double-blind treatment with quetiapine (75, 150,
      300, 600, or 750 mg daily), haloperidol (12 mg daily), or placebo and evaluated
      weekly for 6 weeks. At end point, significant differences (p < 0.05, analysis of
      covariance) in adjusted mean changes from baseline were identified between the
      four highest doses of quetiapine and placebo for BPRS total, BPRS positive
      symptom cluster, and CGI Severity of Illness item scores and between quetiapine
      300 mg and placebo for SANS summary score. Differences between quetiapine and
      haloperidol were not significant. Dose-response modeling showed significant
      linear and quadratic functions of quetiapine dose for all primary efficacy
      variables. Notably, no significant safety concerns were identified as dose
      increased. Quetiapine was no different from placebo across the dose range studied
      regarding incidence of extrapyramidal symptoms or change in prolactin
      concentrations. Quetiapine is well tolerated and clinically effective in the
      treatment of schizophrenia. It is both superior to placebo and comparable to
      haloperidol in reducing positive symptoms at doses ranging from 150 to 750 mg/day
      and in reducing negative symptoms at a dose of 300 mg/day.

PMID- 9270901
TI  - Interaction of the novel antipsychotic drug amperozide and its metabolite FG5620
      with central nervous system receptors and monoamine uptake sites: relation to
      behavioral and clinical effects.
AB  - Behavioral, biochemical, and electrophysiological studies suggest that amperozide
      affects mesolimbic and mesocortical dopamine neurotransmission. The receptor
      binding profile of amperozide is discussed and related to behavioral and
      clinical, i.e., antipsychotic, effects of the drug. As previously reported,
      amperozide displayed high affinity for serotonin 5-HT2A receptors (Ki = 16
      nmol/L), and moderate affinity for striatal dopamine D2 (Ki = 540 nmol/L) and
      cortical alpha 1-adrenergic receptors (Ki = 172 nmol/L). In the present study
      amperozide displayed low affinity for several serotonin receptor subtypes as well
      as for the dopamine D4 receptor transfected in COS7 cells (Ki D4.2 = 769 nmol/L
      and Ki D4.4 = 384 nmol/L). Amperozide was very weak or did not interact with
      several other receptor species including adrenergic, histaminergic, muscarinic,
      benzodiazepine, gamma-aminobutyric acid, amino acid, opiate, and Ca channels;
      however, amperozide was found to compete for [3H]paroxetine binding for the
      serotonin transporter in the nanomolar range (Ki = 49 nmol/L). In vitro and in
      vivo binding potency of amperozide correlates best with behavioral effects,
      indicating 5-HT2A antagonism, although serotonin uptake inhibition may contribute
      to the effects of amperozide on dopamine neurotransmission. The metabolite of
      amperozide, FG5620, displayed 5-10 times lower pharmacologic activity than
      amperozide. These properties of amperozide may suggest that the antipsychotic
      effects of amperozide are mediated by 5-HT2A receptors, although 5-HT uptake
      inhibition and alpha 1-adrenergic receptor-mediated effects may be considered,
      particularly at higher doses.

PMID- 9270902
TI  - Effects of clozapine on sleep: a longitudinal study.
AB  - Polysomnographic studies on the effects of clozapine, an atypical antipsychotic
      agent with strong sedative properties, on night sleep report inconsistent
      results. Most of these studies did not include baseline recordings and were not
      controlled for clozapine-induced fever, which is known to alter nocturnal sleep.
      We conducted a 2-week longitudinal polysomnographic investigation in 10 long-term
      drug-free schizophrenic patients prior to and at the end of the first and second
      weeks of clozapine treatment. Rectal temperature was measured daily and patients
      with fever (> 37.9 degrees C) were excluded. Clozapine significantly improved
      sleep continuity. In addition, non-rapid eye movement (NREM) sleep and in
      particular stage 2 sleep increased significantly, while the amounts of stage 4
      and slow-wave sleep decreased significantly. Clozapine increased significantly
      REM density, but it did not affect the amount of REM sleep. We conclude that in
      patients who do not experience clozapine-induced fever, clozapine has strong
      sleep consolidating effects resulting from an increase in stage 2 NREM sleep.

PMID- 9270903
TI  - First night effect in depression: new data and a new approach.
AB  - Polysomnography was performed in 20 depressed patients and 8 normal controls for
      2 consecutive nights. A subset of patients had 3 consecutive nights. Patients
      were assigned to groups according to the presence (group I) or absence (group II)
      of a first night effect (REM sleep latency on the first night in the laboratory
      was at least 30 min longer than on the second night). The groups were equivalent
      with regard to gender distribution, age, and severity of depression. In group I,
      REM sleep latency on nights 2 and 3 was significantly shorter than in group II.
      REM sleep percentage on the second night in group I was increased compared to the
      first night. A shift of REM sleep to the first cycle was prominent on the first
      night only in patients with a first night effect. On average, delta sleep was
      preserved in group I compared to group II. We suggest that the first night effect
      reflects a physiological system with greater capacity to respond adaptively and
      to preserve homeostasis when confronted with environmental stressors.

PMID- 9270904
TI  - Reward dependence is positively related to urinary monoamines in normal men.
AB  - According to Cloninger, three major personality dimensions, novelty seeking, harm
      avoidance, and reward dependence, are dependent on central monoaminergic systems.
      This study examined the relationship between the urinary levels of different
      monoamines and the above personality dimensions. Fifty normal men answered the
      Tridimensional Personality Questionnaire (TPQ); their levels of dopamine,
      norepinephrine, epinephrine, normetanephrine, metanephrine, 3-methoxy-4
      hydroxyphenylglycol, vanilmandelic acid, homovanilic acid, and serotonin
      metabolite 5-hydroxyindolacetic acid were measured in urine on two consecutive
      nights. Significant and positive correlations were found between reward
      dependence, 3-methoxy-4-hydroxyphenylglycol, and epinephrine (r = .50 and r =
      .51, respectively). Monoamine levels explained 44% of the variance of reward
      dependence. Cluster analysis identified three groups of subjects presenting
      specific patterns of monoamine excretion. The TPQ scores could discriminate among
      subjects belonging to these clusters. These results point out a narrow
      relationship between urinary monoamine excretion and the basic personality
      dimension of reward dependence.

PMID- 9270905
TI  - No evidence for an association of affective disorders with high- or low-activity
      allele of catechol-o-methyltransferase gene.
AB  - Catechol-o-methyltransferase (COMT) is an enzyme that inactivates biologically
      active or toxic catechols. Previous studies have yielded inconsistent results on
      the relationship between erythrocyte COMT activity and affective disorders.
      Recently an amino acid change (Val-108-Met) of the COMT protein was shown to
      determine high- and low-activity alleles of the enzyme. Using polymerase chain
      reaction and the restriction enzyme NLaIII, we genotyped 107 patients with
      bipolar disorder, 62 with unipolar depression, and 121 controls. Neither bipolar
      nor unipolar patients differ significantly in the genotypic or allelic frequency
      from the control group. Even when the bipolar and unipolar patients were pooled
      into a single group, the distributions of both the genotypes and the alleles for
      the patient group were similar to those for the controls. We conclude that
      genetic variation that determines high and low activities of COMT does not have a
      major effect on the vulnerability to affective disorders in our sample.

PMID- 9270906
TI  - Association of N-acetyl-beta-glucosaminidase levels with seriousness of suicide
      attempts.
AB  - We hypothesized that levels of N-acetyl-beta-glucosaminidase (NAG) would differ
      between patients making serious versus nonserious suicide attempts. The levels of
      NAG from 7 patients hospitalized for serious suicide attempts were compared to 3
      patients whose suicide attempts were not rated serious. There was a significant
      difference in the mean NAG levels of the serious suicide attempters and the
      nonserious attempters, 25 versus 61; p = .036. Implications of this finding are
      discussed.

PMID- 9270907
TI  - Elevated platelet factor 4 and beta-thromboglobulin plasma levels in depressed
      patients with ischemic heart disease.
AB  - Clinical depression has recently been recognized as an independent risk factor
      for cardiac mortality in patients after myocardial infarction. The underlying
      mechanisms of this increased mortality remain unclear. This study investigated
      the hypothesis that patients suffering from ischemic heart disease (IHD) and
      depression concurrently may have abnormal platelet activation resulting in an
      increased risk of thrombosis. Platelet factor 4 (PF4) and beta-thromboglobulin
      (beta-TG) were measured in young healthy control subjects, in nondepressed
      patients with IHD, and in depressed patients with IHD. Mean PF4 and beta-TG
      plasma levels in the IHD group with depression were found to be significantly
      higher than those of the control and IHD groups. This increase was not related to
      age, gender, racial difference, aspirin use, or severity of cardiac disease. This
      finding suggests that in depressed patients with IHD there is greater platelet
      activation, and may indicate an increased risk of thrombotic complications.

PMID- 9270908
TI  - Apolipoprotein E4 in schizophrenia: a study of one hundred sixteen cases with
      concomitant neuropathological examination.

PMID- 9270909
TI  - A clinical study of Kleine-Levin syndrome with evidence for hypothalamic
      pituitary axis dysfunction.

PMID- 9270910
TI  - Thyroid function tests in first-episode bipolar disorder manic and mixed types.

PMID- 9270911
TI  - Social dominance as a confounding factor in studies of primate aggression and
      serotonin.

PMID- 9270912
TI  - Cytokines in schizophrenia.

PMID- 9270913
TI  - What role can endoscopy play in the management of biliary complications after
      laparoscopic cholecystectomy?
AB  - BACKGROUND AND STUDY AIMS: This study was carried out to establish the
      indications for biliary endoscopy due to biliary complications after laparoscopic
      cholecystectomy (LC). PATIENTS AND METHODS: One hundred nineteen patients (36
      men, 86 women; median age 59, range 16-93) were referred for endoscopic
      retrograde cholangiopancreatography (ERCP) to five centers between 1990 and 1994,
      and included in the study. The delay between LC and ERCP was 105 +/- 21 days.
      RESULTS: Four types of complications were observed. a) Fifty-seven patients had
      residual stones or clip migration into the common bile duct (CBD); all were
      successfully treated with endoscopic sphincterotomy (ES). b) Twelve major
      injuries to the CBD were diagnosed by ERCP; successful surgical repair was
      carried out in most of these cases. c) Twenty patients had a partial biliary
      stricture; endoscopic stenting was attempted as a primary procedure in eight
      patients, with a satisfactory outcome in five (63%). d) Thirty patients had a
      bile leak; endoscopic therapy (26 patients) led to recovery in 18 (69%). The
      benefit of endoscopic treatment was less clear in five (19%); ES failed to bring
      about improvement in three patients (12%). CONCLUSIONS: ERCP is indicated when a
      biliary complication is suspected after laparoscopic cholecystectomy. Endoscopic
      sphincterotomy is effective for the treatment of retained stones, clip migration,
      and bile leakage. Endoscopic stenting may be offered as a primary option in
      partial CBD strictures.

PMID- 9270914
TI  - Diagnostic strategies for extrahepatic cholestasis of indefinite origin:
      endoscopic ultrasonography or retrograde cholangiography? Results of a
      prospective study.
AB  - BACKGROUND AND STUDY AIMS: Due to its lower morbidity, it has been suggested that
      endoscopic ultrasonography (EUS) might replace endoscopic retrograde
      cholangiography (ERC) in the management of extrahepatic cholestasis of unknown
      origin. The present study aimed to compare the diagnostic accuracy of EUS and ERC
      in the management of cholestasis of unknown origin, taking into account the
      patient's general status and the necessity of endoscopic therapy. PATIENTS AND
      METHODS: Sixty-eight patients with cholestasis of unknown origin were studied
      prospectively. EUS followed by ERC was carried out on a blinded basis by two
      endoscopists; diagnostic and therapeutic suggestions were made after either
      examination. During the ERC procedure and before withdrawing the tube, the
      endoscopist provided the final conclusions and carried out appropriate endoscopic
      treatment. RESULTS: A correct diagnosis was obtained with EUS and ERC in 94% and
      in 92% of cases, respectively (not significant). After EUS, diagnostic ERC was
      necessary for diagnosis and therapy in 24% and 58% of cases, respectively. After
      ERC, EUS was requested in 41% of cases. The higher the American Society of
      Anesthesiologists (ASA) grade, the less it was necessary to perform a
      complementary investigation. In ASA grade 1 patients, endoscopic therapy was
      suggested in 38% of cases after EUS and in 33% after ERC (not significant); in
      ASA grade 3 patients, it was suggested in 93% of cases. CONCLUSIONS: The
      diagnostic sensitivities of EUS and ERC are similar for extrahepatic cholestasis.
      ERC is first indicated in poor candidates for surgery, since endoscopic therapy
      is frequently required. In good candidates for surgery, EUS should be carried out
      first in order to stage a tumor or identify choledocholithiasis.

PMID- 9270915
TI  - Diagnosing extrahepatic bile duct stones using intraductal ultrasonography: a
      case series.
AB  - BACKGROUND AND STUDY AIMS: Intraductal ultrasonography (IDUS), a new
      ultrasonographic diagnostic procedure, was used to assess the presence of
      extrahepatic bile duct stones. PATIENTS AND METHODS: The IDUS apparatus consisted
      of a 6-French high-frequency (20 MHz) probe. Prior to clinical application, in
      vitro studies were conducted in a water tank. Clinically, IDUS was successful in
      31 patients after endoscopic retrograde cholangiography. Interpretations of IDUS
      images were evaluated in comparison with cholangiographic and fluoroscopic
      findings. RESULTS: Experimental testing demonstrated that stones or fragments
      were typically visualized as strong, high-echo images with acoustic shadowing;
      air bubbles were seen as fan-shaped high-echo areas or comet-shaped high-echo
      areas; and sludge was visualized as soft, easily changing, high-echo structures.
      Extrahepatic bile duct stones were visualized by IDUS in 30 of 31 patients
      (96.8%), while fluoroscopy and cholangiography identified 19 (61.3%) and 25
      (80.6%), respectively. Accurate differentiation between stones and air bubbles
      was also possible. CONCLUSION: IDUS could be a useful modality in the diagnosis
      of extrahepatic bile duct stones.

PMID- 9270916
TI  - Possibilities and limitations of endoscopic resection for early gastric cancer.
AB  - BACKGROUND AND STUDY AIMS: To date, the accepted criteria for endoscopic
      resection of early gastric cancer have been: a) elevated-type mucosal cancer less
      than 2 cm in size, and b) depressed-type mucosal cancer without ulceration less
      than 1 cm in size. In this study, we attempted to expand these indications.
      PATIENTS AND METHODS: Sixty patients with early gastric cancer who did not meet
      the above criteria underwent endoscopic treatment, and were divided into four
      groups: those with elevated tumours larger than 2 cm with submucosal invasion
      (group 1 a); those without submucosal invasion (group 1 b); those with depressed
      tumours larger than 1 cm (group 2); and those with ulcerated tumours (group 3).
      The patients were treated with endoscopic resection using a two-channel scope,
      followed by additional laser irradiation or heater-probe coagulation (combination
      therapy) if residual cells were found. Follow-up was by endoscopy and biopsy for
      more than two years. RESULTS: Endoscopic treatment was effective in 87% of the
      patients (52 of 60), half of whom required combination therapy. In submucosal
      cancers, endoscopic treatment was effective in 76% of patients (13 of 17).
      However, tumours with deep invasion into the submucosa could not be cured.
      Mucosal cancers larger than 20 mm could be completely resected in 44% of patients
      (eight of 18) using endoscopic resection, but all five patients with tumours
      larger than 30 mm had incomplete resections. CONCLUSIONS: These results indicate
      that complete resection using endoscopic resection alone is possible in early
      gastric cancers measuring up to 30 mm in diameter. Tumours larger than 30 mm, and
      those with deep submucosal invasion, cannot be curatively treated by the current
      endoscopic modalities.

PMID- 9270917
TI  - Mechanisms producing color change in flat early gastric cancers.
AB  - BACKGROUND AND STUDY AIMS: Although highly refined endoscopes have made it
      possible to detect not only early gastric cancers with morphological changes, but
      also flat-type tumors (type IIb) on the basis of the color changes observed in
      them, the factors responsible for color changes in type IIb carcinomas have not
      been fully elucidated. The aim of this study was to analyze the potential
      mechanisms underlying these color changes. PATIENTS AND METHODS: Thirteen type
      IIb cancers were selected from a total of 589 resected gastric cancers detected
      preoperatively using endoscopic examination. All of the tumors showed color
      changes alone, without surface changes, and the color changes included redness,
      discoloration, and spotty bleeding. Detailed histological examination of the
      resected stomachs revealed twelve more II b lesions that had not been identified
      at endoscopy. The endoscopic appearance of the IIb cancers were correlated with
      the degree of tumor differentiation, the extent of wall infiltration, and the
      number of capillaries. RESULTS: In cases that were detectable by endoscopy, the
      endoscopic color appearance correlated significantly with both tumor size (P <
      0.02) and with the extent of mucosal cancer infiltration (P < 0.02). Histological
      examination of the IIb lesions revealed that redness and discoloration were
      significantly more frequent in the differentiated and undifferentiated cancer
      types, respectively (P < 0.01). There was a significant difference in the number
      of capillaries between type IIb carcinoma and the adjacent normal mucosa, but not
      between cancers. The numbers for differences in redness and discoloration were
      7.0 +/- 5.6 and -14.0 +/- 8.8, respectively. CONCLUSIONS: These results suggest
      that the main factor underlying color change in type IIb early gastric cancers
      may be the number of capillaries in the lesions, in comparison with the adjacent
      mucosa. Whether the lesion is visible on endoscopy, however, depends more on its
      size than on the number of capillaries.

PMID- 9270918
TI  - Automatic washer disinfector for flexible endoscopes: a new evaluation process.
AB  - BACKGROUND AND STUDY AIMS: Many automatic washer disinfectors for flexible
      endoscopes have been marketed and offered as an alternative method of preventing
      infections, but they are frequently unsatisfactory. There is therefore clearly a
      need to test prototypes prior to marketing, following an evaluation process that
      is sufficiently reliable and rigorous to guarantee the efficacy of the
      decontamination processes. MATERIALS AND METHODS: The present study describes an
      experimental method based on the follow-up of the decontamination of a Tygon
      tube, the internal surface of which was contaminated by a bacterial biofilm. This
      method is proposed as a preliminary test for evaluating washer disinfectors.
      RESULTS: An analysis of the results obtained after technical modifications of the
      first prototype of the Fibro-Cleaner showed that complementary activities of each
      successive cycle phase allow a reduction in the number of adherent bacteria of
      more than 8 log per cm2 of support. With the three different biofilms tested
      (Escherichia coli, Pseudomonas aeruginosa mucoid and Staphylococcus aureus), no
      microorganisms were recovered from the support at the end of the decontamination
      process. CONCLUSIONS: The experimental protocol suggested here seems to be well
      suited for assessing washer disinfectors during the development phase of the
      prototype, as well as for comparative studies.

PMID- 9270919
TI  - Endoscopic snare mucosectomy in the esophagus without any additional equipment: a
      simple technique for resection of flat early cancer.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection of early esophageal
      cancer has increasingly proved to be an effective treatment modality, especially
      if the tumor has not invaded the muscularis mucosae. Different techniques have
      been introduced, using an overtube, double-channel endoscope, or suction cap. We
      have not found that these devices are required for snare resection in the
      esophagus. PATIENTS AND METHODS: Over a period of two years (1994-1996), seven
      patients (five men and two women, age range 59-88) with early esophageal cancer
      defined by endosonography (3 cm or less in size, limited to the submucosal layer)
      were treated using a simplified technique of endoscopic snare resection using a
      monopolar diathermic polypectomy snare made of monofilament steel wire. The snare
      was positioned around the lesion, and then closed while pressing the snare
      against the mucosa and applying suction to draw the lesion into the snare. Pure
      coagulation current was used for resection. If necessary, a piecemeal technique
      was used to achieve complete removal. RESULTS: Complete removal was achieved in
      one session in all seven cases. No complications were observed. Two patients
      underwent radical surgery with no tumor remnant or metastatic lymph node in the
      resected specimen. All patients have remained free of recurrence during a median
      follow-up period of seven months (range 3-22 months). Two patients died of
      cardiovascular disease four and eight months after endoscopic mucosal resection.
      CONCLUSION: Small early esophageal cancer can be safely removed with a simplified
      method of endoscopic snare resection using a standard monofilament polypectomy
      snare.

PMID- 9270920
TI  - Endosonography-guided fine-needle biopsy of indurated pancreatic lesions using an
      automated biopsy device.
AB  - BACKGROUND AND STUDY AIMS: We have designed and evaluated a prototype automated
      spring-loaded biopsy needle for endoscopic ultrasonography (EUS)-guided tissue
      sampling of indurated lesions in which sampling using conventional aspiration
      needles has failed. PATIENTS AND METHODS: EUS-guided fine-needle biopsy using the
      new device was performed in four patients (two men, two women, mean age 65 years)
      with indurated pancreatic lesions that could not be penetrated with a
      conventional manually operated aspiration needle. The lesions were located in the
      head of the pancreas in two patients, in the genu in one, and in the body in one.
      RESULTS: The automatic biopsy needle allowed penetration of the pancreatic
      lesions in all cases. The biopsy route was transduodenal in two patients, and
      transgastric in the other two. The biopsies provided a core specimen for
      histological and cytological diagnosis in all cases. No complications occurred.
      CONCLUSION: The spring-loaded biopsy needle allows tissue sampling of indurated
      pancreatic lesions that cannot be penetrated with conventional aspiration
      needles. Further studies are warranted to determine whether this device can
      improve the results of EUS-guided fine-needle aspiration biopsy.

PMID- 9270921
TI  - Endoscopic therapy of complications following laparoscopic cholecystectomy: how
      much can we expect?

PMID- 9270922
TI  - Self-expanding metal stents for palliation of stenosing tumors of the esophagus
      and cardia: a critical review.

PMID- 9270923
TI  - Endoscopic ultrasonography in portal hypertension.

PMID- 9270924
TI  - Lower intestinal hemorrhage due to a dislodged metallic stent.
AB  - A case of a 72 year old man is reported who developed a choledochoduodenal
      fistula due to distal biliary obstruction by a tumor of the papilla. A metal
      stent, introduced through this fistula into the common bile duct, dislodged and
      passed spontaneously with the feces. Plastic stents were then successfully
      inserted.

PMID- 9270925
TI  - Postoperative ischemic jejunal stenosis treated with balloon catheter dilation
      and Wallstent implantation.
AB  - Ischemic stenosis of the jejunum is rare. For technical, anatomical, and
      pathological reasons, ischemic stenosis of the jejunal segment used for the
      replacement of the esophagus or the stomach, or both, represents a special
      entity. The present study reports a case of balloon catheter dilation of ischemic
      strictures of the jejunal segment, used for substitution after gastrectomy. In
      this patient, an occlusion of the blood vessels supplying the affected segment
      was observed at its aortic origin, and a Wallstent was implanted. A rare late
      complication, aortoesophageal fistula, appeared one year after placement of the
      Wallstent. The case presented in this study suggests that using balloon catheters
      and implanting a Wallstent may be a useful approach to the management of
      postoperative ischemic strictures of the jejunum in selected cases. The minimally
      invasive technique with special indications used here has not previously been
      described. The rare complication mentioned, however, requires special attention.

PMID- 9270926
TI  - A severe complication of the new self-expanding spiral nitinol biliary stent.
AB  - The new spiral nitinol biliary stent offers some very promising features,
      including its long patency and retrievability. We report here the case of a
      patient in whom this type of stent was inserted for palliative treatment of a
      periampullary tumour. The stent migrated distally, and could not be withdrawn.
      The further course was complicated by duodenal obstruction, repeated bouts of
      cholangitis, and fatal hemorrhage after surgical removal of the endoprosthesis.
      The design of this new stent should be improved.

PMID- 9270927
TI  - Massive hemorrhage caused by a perforating Gianturco-Z stent resulting in an
      aortoesophageal fistula.
AB  - Endoscopic placement of self-expanding metal stents is regarded as a safe and
      effective method of palliating obstructive esophageal malignancies. We report
      here the case of a 49-year-old woman with an inoperable squamous-cell carcinoma
      located in the mid-esophagus. After two courses of chemotherapy, a silicone
      covered Gianturco-Z stent was placed because of progressive tumor growth.
      Eighteen days after the stent placement, the patient presented with hematemesis,
      and died 24 hours after admission. At autopsy, the proximal end of the stent was
      found to have perforated through the normal esophageal mucosa into the aorta,
      resulting in an aortoesophageal fistula. This complication should be considered
      in patients who present with massive hemorrhage after undergoing radiotherapy or
      chemotherapy, or both, before stent placement in the mid-esophagus.

PMID- 9270928
TI  - Recurrence of biliary drug lithiasis due to dipyridamole.
AB  - The occurrence of drug-containing gallstones is not often observed. To our
      knowledge, three drugs have so far been incriminated-ceftriaxone, glaphenine, and
      dipyridamole. This report presents the case of an 85-year-old woman who developed
      a recurrent drug-containing gallstone caused by dipyridamole eighteen months
      after a previous stone had been removed endoscopically.

PMID- 9270930
TI  - Endoscopic balloon dilation of strictures complicating solitary rectal ulcer
      syndrome.

PMID- 9270929
TI  - Small-bowel obstruction during enzymatic treatment of gastric bezoar.
AB  - A 66-year-old woman had a sudden onset of small-bowel obstruction during
      enzymatic treatment for gastric persimmon bezoar. Oral enzymatic therapy is the
      most effective method of treatment for large phytobezoars when endoscopic
      extraction is not possible. However, this report suggests that a further
      endoscopic intervention may be necessary in case the dissolved bezoars cause
      small-bowel obstruction during this form of therapy.

PMID- 9270931
TI  - A simple test for predicting patients' tolerance of upper gastrointestinal
      endoscopy.

PMID- 9270932
TI  - Comment on Gonvers, "appropriateness and diagnostic yield of upper
      gastrointestinal endoscopy".

PMID- 9270933
TI  - Stent-in-tube: self-expanding metal stent in the management of a partially eroded
      Atkinson's oesophageal prosthesis.

PMID- 9270934
TI  - A new multipurpose tube for esophageal endoscopy.

PMID- 9270935
TI  - Treatment of a submucosal hemangioma of the esophagus using simultaneous video
      assisted thoracoscopy and esophagoscopy: description of a new minimally invasive
      technique.

PMID- 9270936
TI  - Bronchoesophageal fistula as a complication of cytomegalovirus esophagitis in
      AIDS.

PMID- 9270937
TI  - Endoscopic management of food-filled duodenal diverticulum mimicking a pancreatic
      tumour.

PMID- 9270938
TI  - Endoscopically performed cystoduodenal drainage of a pancreatic pseudocyst after
      Billroth II gastrojejunostomy: a case report.

PMID- 9270939
TI  - Therapeutic endoscopic retrograde cholangiopancreatography with ultra-short
      fluoroscopy: report of two cases.

PMID- 9270940
TI  - Selective biliary opacification through the proximal opening of a sphincterotome
      inserted into the pancreatic duct: a new pitfall?

PMID- 9270941
TI  - Endoscopic removal of a lymphangioma of the colon: case report of the diagnostic
      value of an endoscopic ultrasound probe.

PMID- 9270942
TI  - Hemostasis by capping bleeding diverticulum of the colon with clips.

PMID- 9270943
TI  - Looking beyond age and race: the structure of networks, functions of support, and
      chronic stress.

PMID- 9270944
TI  - Age at and time since: modeling temporal aspects of exposure.

PMID- 9270945
TI  - Cardiovascular event classification in the very old: how accurate and how
      complete?

PMID- 9270946
TI  - Change in social ties and subsequent mortality in rural elders.
AB  - Prior studies assessing social ties and mortality risk in older persons have not
      considered the dynamic nature of social ties, health, and functional status in
      this age group. We evaluated the association between change in social ties
      (assessed in 1982 and 1985) and subsequent mortality through 1993 in a population
      based cohort of 2,575 rural persons ages 65-102 years. The same summary measure
      of social ties was constructed for both interviews and included marital status,
      number of close friends and relatives, church attendance, and membership in a
      group. Compared with persons reporting higher levels of social ties at both
      interviews, a decrease to a low level of social ties was associated with an
      increased mortality risk for both men [hazard ratio (HR) = 1.8; 95% confidence
      interval (CI) = 1.2-2.7] and women (HR = 2.1; 95% CI = 1.5-3.0). Lower levels of
      social ties at both interviews were also associated with greater mortality risk
      in men (HR = 2.2: 95% CI = 1.5-3.1) and women (HR = 2.2; 95% CI = 1.6-2.9),
      whereas an increase to a higher level of social ties was not associated with
      subsequent mortality risk. Adjustment for age, education, smoking status,
      cognitive function, onset of a major illness, change in physical function, change
      in self-perceived health status, and change in depressive symptoms eliminated the
      association between loss of social ties and survival, but both men (HR = 2.3; 95%
      CI = 1.5-3.5) and women (HR = 1.8; 95% CI = 1.2-2.6) reporting low levels of
      social ties at both interviews remained at elevated risk. The lack of an
      association between loss of social ties and mortality risk after adjusting for
      demographic, health, and functional status variables indicates that these are
      either confounding or intervening variables in a social ties and mortality
      association. In contrast, sustained low levels of social ties appear to influence
      mortality risk independent of these same variables and imply that continued
      social isolation may be a more important determinant of mortality risk than
      recent changes in social ties.

PMID- 9270947
TI  - Social support, stress, and blood pressure in black adults.
AB  - Psychosocial factors arising from socioeconomic disadvantage and discrimination
      may contribute to the excess risk of elevated blood pressure in African
      Americans. The purpose of this study was to assess the association of social
      support and stress with blood pressure in a community-based sample of 25-to 50
      year-old black adults in Pitt County, NC. A stratified random sample of dwellings
      was selected in 1988, and 1,784 black adults (80% of those eligible) were
      interviewed. Analyses were sex specific and adjusted for age, obesity, and
      waist/hip ratio. In separate analyses of emotional support, instrumental support,
      and stress with blood pressure, all associations were in the predicted direction
      (inverse for support, direct for stress) but were stronger for systolic than for
      diastolic blood pressure. Differences in systolic blood pressure associated with
      low support or high stress ranged from 5.2 to 3.6 mmHg in women and 3.5 to 2.5
      mmHg in men. In simultaneous regression analyses of support and stress, each of
      the separate effects was reduced for women, but a sizable aggregate effect of low
      support and high stress remained [+7.2 mmHg (95% confidence limits = +1.3, +13.1)
      for systolic blood pressure and +4.0 mmHg (95% confidence limits = +0.1, +7.9)
      for diastolic blood pressure.

PMID- 9270948
TI  - Estimating the risk of breast cancer in relation to the interval since last term
      pregnancy.
AB  - We review the analytical methods of studies that asked whether a term pregnancy
      transiently increases a woman's risk of breast cancer. These analyses must
      separate the possible influence of a recent pregnancy from that of two other
      correlated variables, attained age and age at last pregnancy. Most analyses have
      compared women of the same parity. To determine, however, whether the risk of
      breast cancer is different than it would have been had the last pregnancy never
      occurred, it is necessary to compare the risk of breast cancer over time among
      women of parity N+1 with women of parity N, which has been done in a few studies.
      To generate relative risk estimates that are independent of arbitrary coding
      decisions, we show that the analytical models must be more complex than those in
      published studies. We used these models to compare women of parity N and N+1 for
      breast cancer occurrence, using data from the U.S. Cancer and Steroid Hormone
      Study. For the first 6 years after delivery, first term pregnancy was associated
      with lower or unchanged risk of breast cancer, second pregnancy with higher risk,
      third pregnancy with lower risk, and fourth pregnancy with both lower and higher
      risk depending on age at delivery. Given the inconsistent findings between
      adjoining levels of parity and the wide confidence intervals around the
      estimates, we could not find clear evidence for or against the theory that term
      pregnancy is transiently associated with an increased risk of breast cancer.

PMID- 9270949
TI  - Prevalence, determinants, and misclassification of myocardial infarction in the
      elderly.
AB  - We evaluated the prevalence, determinants, and misclassification of different
      types of myocardial infarction in 3,272 men and women age 55 years or older. We
      defined self-reported myocardial infarction with electro-cardiographic evidence
      as "typical myocardial infarction." We defined self-reported myocardial
      infarction without electrocardiographic evidence, but verified with additional
      clinical information, as "non-Q-wave myocardial infarction." Finally, we defined
      myocardial infarction detected by electrocardiogram that was not self-reported as
      "silent myocardial infarction," after verification of absence of symptoms.
      Overall, the prevalence of typical myocardial infarction was 4.1% [95% confidence
      interval (CI) = 3.5-4.9], of non-Q-wave myocardial infarction 2.8% (95% CI = 2.2
      3.4), and of silent myocardial infarction 3.9% (95% CI = 3.2-4.5). Silent
      myocardial infarction was more prevalent in women, hypertensives, cigarette
      smokers, and those with higher post-load blood glucose. Self-reported myocardial
      infarction without electrocardiographic characteristics could be verified as
      myocardial infarction by means of additional clinical information in 56% of the
      cases. We conclude that myocardial infarction occurs frequently in the elderly
      without typical symptoms or electrocardiographic changes. As all these
      manifestations of myocardial infarction convey an increased risk of symptomatic
      heart disease or death, they require further attention. Misclassification due to
      limited sources of information can be considerable and should be taken into
      account in the design and interpretation of epidemiologic studies.

PMID- 9270950
TI  - Circulatory disease mortality in the very elderly.
AB  - I describe circulatory disease mortality in age groups 85 years and over, as
      available from Vital Statistics of the United States. Mortality rates from all
      circulatory disease combined, from ischemic heart disease, and from
      cerebrovascular diseases increase faster with age than the mortality rate from
      all causes combined. The kinds of circulatory diseases causing death change with
      age. Although men and black people have higher mortality rates from circulatory
      diseases than women and white people through early old age, the gaps narrow with
      age, and there are sex and racial crossovers in later old age. Age groups 85
      years and over have had smaller decreases in mortality rates from circulatory
      diseases since 1960 than middle-aged and younger elderly age groups.

PMID- 9270951
TI  - Caffeine intake in relation to the risk of primary cardiac arrest.
AB  - We conducted a population-based case-control study in King County, WA, to
      evaluate the association between usual caffeine intake and primary cardiac
      arrest. We identified primary cardiac arrest cases (N = 362) without a history of
      clinical heart disease or major comorbidity through paramedic incident reports
      during the period 1988-1994. We identified controls (N = 581), individually
      matched to cases on age (+/-7 years) and gender and meeting the same general
      health criteria, through random digit dialing. We interviewed the spouses of
      cases and controls to obtain information on usual caffeine intake from coffee,
      tea, and cola during the prior year. After adjusting for cigarette smoking and
      other risk factors, we observed little association between daily consumption of
      the caffeine equivalent of fewer than 5 cups per day of drip coffee (< 687 mg per
      day) and primary cardiac arrest. High usual caffeine consumption (> or = 687 mg
      per day) was associated with a modestly elevated risk of primary cardiac arrest
      [odds ratio = 1.44; 95% confidence interval (CI) = 0.82-2.53]. The elevated risk
      associated with high caffeine consumption appeared to be restricted to never
      smokers (odds ratio for > or = 687 mg per day = 3.2; 95% CI = 1.3-8.1).

PMID- 9270952
TI  - Moderate maternal alcohol consumption and risk of spontaneous abortion.
AB  - Maternal alcoholism is known to have adverse effects on reproduction and fetal
      development, but the effects of moderate consumption remain controversial. In a
      previous case-control study, we found a doubled risk of spontaneous abortion with
      an average consumption of seven or more drinks per week during the first
      trimester. To confirm this finding while avoiding potential biases from the case
      control design, we examined moderate alcohol consumption in a prospective cohort
      study of over 5,000 pregnant women. An interview in the first trimester asked
      about alcohol consumption during the week before interview ("during the first
      trimester") and before pregnancy. We found an increased risk of spontaneous
      abortion in women who drank more than three drinks per week during the first
      trimester, with an adjusted odds ratio (OR) of 2.3 [95% confidence interval (CI)
      = 1.1-4.5]. The increased risk associated with this moderate alcohol consumption
      may be higher in first than in second trimester abortions, and it is even higher
      in the first 10 weeks (OR = 3.8; 95% CI = 1.7-8.7), based on small numbers.
      Consumption of alcohol before pregnancy was not strongly associated with
      spontaneous abortion.

PMID- 9270953
TI  - Caffeinated beverages, decaffeinated coffee, and spontaneous abortion.
AB  - We examined the relations between spontaneous abortion and the consumption of
      caffeine, individual caffeine-containing beverages (coffee, tea, and soda), and
      decaffeinated coffee in a prospective study of 5,144 pregnant women. We collected
      information about potential risk factors for spontaneous abortion, including
      consumption of caffeinated beverages and decaffeinated coffee before and during
      pregnancy, by interview in the first trimester. Neither total estimated caffeine
      nor individual caffeinated beverage consumption during the first trimester was
      associated with an appreciable increase in risk for spontaneous abortion. The
      adjusted odds ratio for consumption of greater than 300 mg per day of caffeine
      was 1.3 [95% confidence interval (CI) = 0.8-2.1] after adjustment for maternal
      age, pregnancy history, cigarette and alcohol consumption, employment, race,
      gestational age at interview, and marital and socioeconomic status. The adjusted
      odds ratio for spontaneous abortion related to consumption of three or more cups
      of decaffeinated coffee during the first trimester was 2.4 (95% CI = 1.3-4.7) in
      the same model. Although we could not demonstrate this with available data, we
      suspect that this association was due to bias resulting from the relations among
      fetal viability, symptoms of pregnancy such as nausea, and consumption patterns
      during pregnancy.

PMID- 9270954
TI  - Conditions at conception and risk of menstrual disorders.
AB  - In a case-control study, we evaluated the association of the risk of menstrual
      disorders with four periconceptional factors: short preceding interpregnancy
      interval (< 6 months), low (< or = 19 years) or high (> or = 40 years) maternal
      age at conception, and month of conception. We divided 919 women who had visited
      a fertility clinic between 1991 and 1995 into three categories: cases (with mean
      menstrual cycle length > or = 42 or < or = 21 days, or a variation of > or = 14
      days between cycles, or amenorrhea, N = 294), controls (with cycles within a
      range of 25-35 days and variation < or = 7 days, N = 520), and intermediates (N =
      105). A self-administrable questionnaire was mailed, asking for information about
      maternal reproductive history and age, and potential confounders such as smoking,
      exercise, and level of education. Response (77%) differed little among cases,
      intermediates, and controls. We found elevated risks for short pregnancy
      intervals [adjusted odds ratio (OR) = 2.04; 95% confidence interval (CI) = 1.04
      4.02] and advanced maternal age (OR = 3.24; 95% CI = 1.27-8.30) but not for low
      maternal age (OR = 0.58; 95% CI = 0.11-3.14) (cases vs controls). We found
      similar effects for intermediates vs controls. The distribution of month of
      conception did not differ much from controls for both cases and intermediates.
      The results indicate that conception after short pregnancy intervals or at
      advanced maternal age increases the risk of menstrual disorders in daughters. The
      precise etiology is unclear, but it may lie in the quality of the oocyte at
      conception.

PMID- 9270955
TI  - Do standing, lifting, climbing, or long hours of work during pregnancy have an
      effect on fetal growth?
AB  - We assessed prospectively the impact of length of the work week and job activity
      on fetal growth. Among 575 women who worked during pregnancy, neither prolonged
      standing, frequent lifting, or climbing at work, nor a high composite activity
      score showed an association with fetal growth, as measured by birthweight for
      gestational age. Long hours of work, however, did reduce fetal growth. Infants of
      women working long hours late in pregnancy showed decreases in gestation-adjusted
      birthweight of about 80 gm (95% confidence limits = -238, +74 gm), compared with
      women working 20 hours or less. When long hours (> 40 hours per week) were
      combined with job activity, the estimated reductions ranged up to 350 gm. At
      lower weights (< or = 3,000 gm), categorical analyses showed elevated odds ratios
      (1.1-1.8) for climbing, lifting, and long hours and for the combination of
      prolonged standing with a lengthy work week. These results indicate that long
      weeks of physically demanding work could lead to fetal growth reductions that may
      be clinically significant. Consistent with this suggestion, infants of women who
      worked part-time had the highest mean birthweights. Hours of work, not only job
      tasks, may be important for pregnant workers.

PMID- 9270956
TI  - Birth defects among offspring of Norwegian farmers, 1967-1991.
AB  - We investigated birth defects (N = 4,565) reported to the Medical Birth Registry
      of Norway among 192,417 births between 1967 and 1991 to parents identified as
      farmers in five agricultural and horticultural censuses between 1969 and 1989.
      The prevalences at birth of all and specific birth defects deviated little from
      those among 61,351 births to non-farmers in agricultural municipalities. We
      classified exposure indicators on the basis of information provided at the
      agricultural censuses. The main hypotheses were that parental exposure to
      pesticides was associated with defects of the central nervous system, orofacial
      clefts, some male genital defects, and limb reduction defects. We found moderate
      increases in risk for spina bifida and hydrocephaly, the associations being
      strongest for exposure to pesticides in orchards or greenhouses [spina bifida: 5
      exposed cases, odds ratio (OR) = 2.76, 95% confidence interval (CI) = 1.07-7.13;
      hydrocephaly: 5 exposed cases, OR = 3.49, 95% CI = 1.34-9.09]. Exposure to
      pesticides, in particular in grain farming, was also associated with limb
      reduction defects (OR = 2.50; 95% CI = 1.06-5.90). We also saw an association
      with pesticides for cryptorchism and hypospadias. We found less striking
      associations for other specific defects and pesticide indicators, animal farming,
      and fertilizer regimens.

PMID- 9270957
TI  - Arsenic in drinking water and incidence of urinary cancers.
AB  - The associations between arsenic ingestion and cancers of the bladder and kidney
      have been documented in Taiwan. To evaluate further such associations for urinary
      cancers of various cell types, we conducted an ecologic study encompassing 243
      townships using cancer registry data of patients diagnosed between 1980 and 1987.
      We used the proportions of wells with various specified arsenic levels in each
      township as indicators of exposure and evaluated the effects of urbanization and
      smoking by an urbanization index and the number of cigarettes sold per capita. In
      both genders, we observed associations of high arsenic levels in drinking water
      with transitional cell carcinomas of the bladder, kidney, and ureter and all
      urethral cancers combined. We also observed such associations in adenocarcinomas
      of the bladder in males, but not in squamous cell carcinomas of the bladder or
      renal cell carcinomas or nephroblastomas of the kidney. There was also a positive
      association between the urbanization index and transitional cell carcinomas of
      the ureter in males. The number of cigarettes sold per capita was not a good
      predictor for urinary cancers. The results indicate that the carcinogenicity of
      arsenic may be cell type specific.

PMID- 9270958
TI  - Occupational risk factors for subgroups of non-Hodgkin's lymphoma.
AB  - The non-Hodgkin's lymphomas (NHL) are a diverse group of neoplasms of the
      lymphatic system whose incidence has been increasing in recent years. The Centers
      for Disease Control Selected Cancers Study, a population-based case-control study
      of several cancers, included a large number of cases of NHL and a pathology
      review, providing a rare opportunity to study risk factors for groups of NHL
      subtypes. We examined the relation between occupational exposures and three
      subgroups of NHL: small cell diffuse lymphomas (N = 185), follicular lymphomas (N
      = 268), and large cell diffuse lymphomas (N = 526). There were 1,659 controls
      available for comparison. After controlling for demographic variables and
      previously identified risk factors for NHL, we observed two interesting
      associations, one between solvent exposure and small cell diffuse lymphomas [odds
      ratio (OR) = 1.60; 95% confidence interval (CI) = 1.10-2.20], and the other
      between meat packaging/processing and follicular lymphomas (OR = 1.60; 95% CI =
      0.99-2.60). The results of this exploratory analysis are primarily negative. Our
      lack of positive findings may indicate that the subgroups of NHL used may not be
      etiologically distinct and that further work needs to be done to develop an NHL
      classification system that is etiologically informative and useful for
      epidemiologic studies.

PMID- 9270959
TI  - Age when maximum height is reached as a risk factor for breast cancer among young
      U.S. women.
AB  - We evaluated height as a potential risk factor for breast cancer in a case
      control study of 747 young women diagnosed with invasive breast cancer before age
      46 years and 961 control subjects recruited by random digit dialing. We found
      that total height attained did not affect a woman's risk of the disease. The age
      when a women reached her maximum height, however, was a risk factor for breast
      cancer. There was a trend of decreasing risk of breast cancer in relation to
      increasing age of height attainment, culminating in a 30% reduction in the risk
      of breast cancer for women who reached their maximum height when they were 18
      years or older compared with women who reached their maximum height when they
      were 13 years old or less (odds ratio = 0.7; 95% confidence interval = 0.5-1.0).
      Although the age at menarche was correlated with the age at maximum height, the
      effect of age at maximum height persisted after adjustment for age at menarche.
      Previous studies have reported that age at menarche is an important determinant
      of risk, but this study indicates that age when maximum height is reached may be
      another, and possibly more important, landmark of puberty that is related to
      breast cancer risk. The physiologic basis for this claim may lie in the influence
      on breast development of exposure to growth hormone and insulin-like growth
      factor during puberty, and on a decreased time between the end of puberty and a
      woman's first livebirth, both of which are believed to affect a woman's risk of
      breast cancer.

PMID- 9270960
TI  - Socioeconomic status, number of siblings, and respiratory infections in early
      life as determinants of atopy in children.
AB  - Asthma and allergic disorders have been on the increase in recent decades,
      especially among children living in affluent countries; some aspects of the
      "Western" way of life may explain this trend. We evaluated the relation of
      aeroallergen skin test reactivity with socioeconomic status, number of siblings,
      and respiratory infections in early life. We examined a total of 2,226
      schoolchildren, ages 7-11 years, in three areas of Lazio, Italy. Skin prick tests
      were performed to assess atopic status, and self-administered questionnaires were
      completed by the parents. The prevalence of prick test positivity was greater
      among children whose fathers were in the highest educational level than among
      those in the lowest [prevalence ratio (PR) = 1.58; 95% confidence interval (CI) =
      1.21-2.06]. There was also a lower prevalence of atopy among larger sibships (PR
      = 0.38 for subjects with four or more siblings vs those without siblings; 95% CI
      = 0.14-0.99). A history of bronchitis or bronchiolitis before age 2 years was
      weakly associated with an increased risk of atopy, whereas a history of pertussis
      or pneumonia was not. Both the effect of father's education and the influence of
      larger sibship size remained when we adjusted for several potential confounding
      factors, including respiratory infections in early life. We infer that higher
      socioeconomic status and lower sibling number are determinants of atopy in this
      Italian population. Protection arising from early severe respiratory infections
      does not explain this association, although we cannot exclude a role for other
      viral infections.

PMID- 9270961
TI  - Gastric acid, acid-suppressing drugs, and bacterial gastroenteritis: how much of
      a risk?
AB  - Recent studies have reported an association between acid-suppressing drugs
      (histamine H2 receptor antagonists and proton pump inhibitors) and development of
      infectious gastroenteritis. We conducted a case-control study nested in a cohort
      of more than 170,000 ever-users of acid-suppressing drugs to examine the
      association between acid-suppressing drugs and bacterial gastroenteritis, using
      data from the General Practice Research Database in the United Kingdom. We
      identified 374 confirmed cases of bacterial gastroenteritis and 2,000 randomly
      sampled controls from the study cohort. There was little increased risk of
      bacterial gastroenteritis among users of acid-suppressing drugs [relative risk
      (RR) = 1.1; 95% confidence interval (CI) = 0.8-1.4]. Omeprazole "single users"
      had an RR of 1.6 (95% CI = 1.0-2.4), but this effect was not observed among those
      using only omeprazole during the last year (RR = 1.1; 95% CI = 0.7-1.9). We did
      not find any dose or treatment duration response. These data do not support a
      major role for acid reduction in the development of bacterial gastroenteritis.

PMID- 9270962
TI  - Magnetic field exposure assessment in a case-control study of childhood leukemia.
AB  - Epidemiologic evaluation of the relation between magnetic field exposures and
      cancer depends critically on study design, particularly the methods used for
      exposure assessment. We incorporated a complex magnetic field exposure assessment
      protocol into a large incident case-control study of childhood leukemia. We
      measured residential magnetic fields using a standard protocol in current and
      former homes of 638 cases and 620 controls and determined wire codes for 414 case
      control pairs. We chose a time-weighted average of magnetic field measurements in
      each eligible home, weighted by the time the subject lived in each home as the
      main exposure metric for each subject. We found that 24-hour bedroom magnetic
      field measurements adequately characterize children's residential exposure and
      that measuring other rooms contributes only slightly to the estimate of average
      residential exposure to magnetic fields. Front door measured fields provide
      useful exposure information when interior measurements are missing. If feasible,
      measuring multiple homes in which the subject has resided is preferable to
      measuring a single home. A similar distribution of wire codes for controls
      agreeing or refusing to participate in our study implies that risk estimates
      derived from wire code data will not be influenced by response bias.

PMID- 9270963
TI  - Risk factors and the sex differential in coronary artery disease.
AB  - In industrialized countries, the incidence of coronary artery disease is three to
      four times higher in men than in women. Our review examines whether differences
      in the prevalence of, or susceptibility to, various coronary risk factors might
      contribute to this sex differential. Cigarette smoking, hypertension, and
      hypercholesterolemia are risk factors for coronary artery disease in both sexes
      and are present at higher levels in middle-aged men than women. To date, such
      differences have failed to explain the coronary sex differential, although higher
      biological susceptibilities to smoking, blood pressure, and total cholesterol in
      men may also be important. Mean levels of protective high-density-lipoprotein
      cholesterol are higher in women than in men throughout life and may also
      contribute to the sex differential. In addition, men with a female pattern of
      abdominal fat distribution are at lower risk of coronary artery disease than
      those with a male pattern. In diabetic populations, the sex differential is
      greatly reduced, but studies on the effects of hyperinsulinemia and a lower
      insulin resistance in women compared with men are scarce. Prospective studies on
      the effect of fibrinogen and other hemostatic factors in women are also required.

PMID- 9270964
TI  - Evidence that adult life risk factors influence the expression of familial
      propensity to breast cancer.
AB  - In the context of a study in Athens comprising 692 cases and 1,261 controls, we
      have evaluated the effect on breast cancer risk of the joint action of first
      degree relative family history and established adult life risk factors. We
      created a risk score by assigning the value of 1 to women at high risk with
      respect to any of these risk factors and 0 otherwise, and summing these values,
      using weights equal to the excess odds ratio. The odds ratio for a tertile
      increment in the risk score was 1.5 [95% confidence interval (CI) = 1.3-1.8]
      among women without family history, and 2.3 (95% CI = 1.1-5.1) for women with
      family history. Our findings imply that women with a family history of breast
      cancer may benefit disproportionately by reduced exposure to adult life risk
      factors.

PMID- 9270965
TI  - Informed consent in epidemiologic studies involving genetic markers.

PMID- 9270966
TI  - Ethics in environmental epidemiology.

PMID- 9270967
TI  - The effect of cancer on in-hospital mortality in patients admitted for myocardial
      infarction.

PMID- 9270968
TI  - Adequacy of prenatal care utilization.

PMID- 9270969
TI  - Public health professionals and interpersonal violence.

PMID- 9270970
TI  - Public health professionals and interpersonal violence.

PMID- 9270971
TI  - Recombinant antibody fragments that detect enoyl acyl carrier protein reductase
      in Brassica napus.
AB  - Purified Brassica napus enoyl acyl carrier protein reductase (ENR) was used to
      select specific antibodies from a library of antibody fragments, single-chain Fv
      (scFv), displayed on filamentous phage. Analysis of the selected clones by BstNI
      fingerprinting and nucleotide sequencing showed that the scFv were derived from
      three different human VH germline genes. The binding specificities were confirmed
      by Western blots and ELISA. The scFv preparations reacted with B. napus ENR, but
      not with beta-keto reductase, nor enoyl reductase from Escherichia coli. Analysis
      of fragments generated by CNBr treatment indicates that the scFv 3.13 recognized
      an epitope located within the N-terminal 80 amino acids of the enzyme molecule.
      The scFv were used to detect ENR directly in extracts of B. napus seeds.

PMID- 9270973
TI  - Capillary supercritical fluid chromatography--atmospheric pressure chemical
      ionization mass spectrometry of gamma- and alpha-linolenic acid containing
      triacylglycerols in berry oils.
AB  - The effect of the gamma-linolenic acid (18:3n-6) residue on the elution of
      triacylglycerols on a 25% cyanopropyl-25% phenyl-50% methylpolysiloxane
      stationary phase was confirmed by using capillary supercritical fluid
      chromatography-atmospheric pressure chemical ionization mass spectrometry [cSFC
      (APCI)MS]. The general elution rule on this stationary phase is that
      triacylglycerols having the same ACN + 2n value coeluted (ACN = acyl carbon
      number and n = combined number of double bonds in the acyl chains). The different
      effect of gamma- and alpha-linolenic acid residues on the retention of
      triacylglycerols and the use of cSFC-(APCI)MS allowed the study of the number of
      different linolenic acid residue isomer combinations in triacylglycerols with an
      identical ACN and degree of unsaturation. Stearidonic acid (18:4n=3) residue was
      found to have a similar effect on the retention behavior of triacylglycerols as
      that of gamma-linolenic acid residue. The abundance of the [M - RCOO]+ ion,
      formed by the loss of one fatty acid moiety of a triacylglycerol, was found to be
      clearly higher in the case of gamma-isomer of the linolenic acid than that of
      alpha-isomer in the identical regiospecific position. This indicates that the
      distance of the double bonds from the glycerol backbone in the acyl chain affects
      the stability of a triacylglycerol molecule in the (APCI)MS system. The
      triacylglycerol composition and the fatty acid combinations of triacylglycerols
      were found to be almost identical in black currant (Ribes nigrum) and alpine
      currant (R. alpinum) seed oils.

PMID- 9270972
TI  - Use of cyclodextrin to deliver lipids and to modulate apolipoprotein B-100
      production in HepG2 cells.
AB  - 2-Hydroxypropyl-beta-cyclodextrin (cyclodextrin), cyclodextrin-solubilized
      oleate, and cyclodextrin-solubilized cholesterol were used to modulate
      proteolysis and secretion of newly-synthesized apolipoprotein B-100 (apoB) in
      HepG2 cells. Following cyclodextrin and lipid treatments, cells were pulse
      labeled with [3H] leucine, and quantitative immunoprecipitation was used to
      measure apoB synthesis, apoB secreted into the medium, and the cellular content
      of undegraded apoB that was not secreted. Three-hour treatment with cyclodextrin
      solubilized oleate (0.2 mM) increased secreted apoB from 4% (control cells) to
      32% and cellular undegraded apoB from 15% (control cells to 64% of apoB
      synthesized, which is consistent with earlier studies using bovine serum albumin
      to complex exogenous oleate. Prolonged daily (4 d or more) administration of 0.5%
      (3.5 mM) cyclodextrin with medium containing 10% fetal bovine serum increased the
      secretion of nascent apoB from 5-10% (control) to 17-28% and cellular undegraded
      apoB from 15-20% (control) to 25-31% of apoB synthesized, respectively.
      Subsequent administration of cyclodextrin solubilized cholesterol (10-40
      micrograms) for only 3 h reversed the cyclodextrin-mediated increase in apoB
      secretion. The application of 0.5% cyclodextrin to HepG2 cells can rapidly
      (within minutes) stimulate cholesterol efflux, and transiently (over a 1-2 d
      period) increase cholesterol synthesis. In the current studies, the cyclodextrin
      mediated increase in cholesterol synthesis was not concurrent with the increase
      in apoB secretion. However, prolonged (15 d) administration of cyclodextrin was
      shown to increase the cellular free cholesterol concentration by 25-41%, reduce
      the cellular triglyceride concentration by 59%, and increase apoB secretion 3- to
      4-fold, without affecting the cellular cholesteryl ester concentration. In
      comparison, 14-d treatment with cyclodextrin-solubilized cholesterol (20
      micrograms/mL) followed by 1-d equilibration without cholesterol was shown to
      increase the cellular free cholesterol and cholesteryl ester concentrations by
      76% and 10-fold, respectively, although apoB secretion was not affected. It is
      hypothesized that chronic daily administration of 0.5% cyclodextrin increased the
      cellular cholesterol concentration and flux in discrete putative regulatory
      compartments, which "shielded" nascent apoB from rapid proteolysis and
      facilitated apoB secretion. In conclusion, cyclodextrin was used independently
      and in combination with cholesterol or oleate to modulate apoB proteolysis and
      secretion. We speculate that subcellular changes in cholesterol concentration and
      flux may modulate apoB production in HepG2 cells.

PMID- 9270974
TI  - Characterization of polar and nonpolar seed lipid classes from highly saturated
      fatty acid sunflower mutants.
AB  - The seed lipids from five sunflower mutants, two with high palmitic acid
      contents, one of them in high oleic background, and three with high stearic acid
      contents, have been characterized. All lipid classes of these mutant seeds have
      increased saturated fatty acid content although triacylglycerols had the highest
      levels. The increase in saturated fatty acids was mainly at the expense of oleic
      acid while linoleic acid levels remained unchanged. No difference between mutants
      and standard sunflower lines used as controls was found in minor fatty acids:
      linolenic, arachidic, and behenic. In the high-palmitic mutants palmitoleic acid
      (16:1n-7) and some palmitolinoleic acid (16:2n-7, 16:2n-4) also appeared.
      Phosphatidylinositol, the lipid with the highest palmitic acid content in
      controls, also had the highest content of palmitic or stearic acids, depending on
      the mutant type, suggesting that saturated fatty acids are needed for its
      physiological function. Positional analysis showed that mutant oils have very low
      content of saturated fatty acids in the sn-2 position of triacylglycerols,
      between the content of olive oil and cocoa butter.

PMID- 9270975
TI  - Lipids and ultrastructure of Thraustochytrium sp. ATCC 26185.
AB  - As a representative of a genus with species considered to be potential commercial
      producers of the nutritionally important polyunsaturated fatty acid
      docosahexaenoic acid (DHA), Thraustochytrium sp. ATCC 26185 was investigated to
      determine its potential for DHA production and lipid composition. Cells from
      liquid shake cultures contained 32% (w/w) lipid, 18% of which was nonsaponifiable
      lipid. The major saturated fatty acids (14:0 and 16:0) comprised up to 59% of the
      total fatty acids, and DHA was up to 25% after 6 d incubation. Squalene
      represented 63% of the nonsaponifiable lipid, and cholesterol composed 41% of the
      total sterols. The phospholipids expected for eucaryotic microbes were detected
      with phosphatidylcholine as the major phospholipid at 76% of the total. The
      ultrastructure of this species was similar to other Thraustochytrium species
      except that the cells did not have surface scales and they contained unusual
      membrane-like structures that appeared to be associated with oil formation.

PMID- 9270976
TI  - On the interrelationship between hepatic carnitine, fatty acid oxidation, and
      triglyceride biosynthesis in nephrosis.
AB  - The nephrotic syndrome is associated with disturbances in plasma lipid pattern
      and metabolism. However, the reason for these perturbations is poorly understood.
      In the present study, we have investigated hepatic triglyceride metabolism in
      puromycin aminonucleoside-induced nephrotic syndrome in rats. Nephrotic rats
      displayed a 70% increase in hepatic triglyceride levels compared to controls
      (16.9 +/- 1.6 vs. 9.8 +/- 0.6 mumol/g liver; means +/- SEM, P < 0.01). The
      capacity for hepatic mitochondrial beta-oxidation of fatty acids was
      substantially elevated (80%). This was associated with a rise in the liver
      content of the fatty acid carrier carnitine (1.24 +/- 0.06 vs. 0.85 +/- 0.07
      mumol/g dry weight, P < 0.05). A positive correlation between the levels of
      acetylcarnitine and acetyl-CoA was found in normal as well as in nephrotic rats,
      implying that carnitine plays an important role as an acetyl group acceptor in
      the liver under normo- and hyperlipidemic conditions. Changes in carnitine levels
      seem to be tightly coupled to the rate of fatty acid oxidation. There was a
      significant elevation in the activity of phosphatidate phosphohydrolase (E.C.
      3.1.3.4) in liver microsomes from nephrotic rats (1.07 +/- 0.09 vs. 0.81 +/- 0.04
      nmol/min.mg protein, P < 0.02). Hepatic very low density lipoprotein (VLDL)
      triglyceride secretion rate was 18% higher in nephrotic rats than in controls.
      The results demonstrate a deranged hepatic triglyceride metabolism in nephrosis,
      with an increased hepatic triglyceride biosynthesis, a sizable accumulation of
      hepatic triglycerides, and only a modest increase in VLDL triglyceride secretion.
      In addition, mitochondrial beta-oxidation of fatty acids was enhanced, associated
      with an increased availability of carnitine.

PMID- 9270977
TI  - Effect of conjugated linoleic acid on body composition in mice.
AB  - The effects of conjugated linoleic acid (CLA) on body composition were
      investigated. ICR mice were fed a control diet containing 5.5% corn oil or a CLA
      supplemented diet (5.0% corn oil plus 0.5% CLA). Mice fed CLA-supplemented diet
      exhibited 57% and 60% lower body fat and 5% and 14% increased lean body mass
      relative to controls (P < 0.05). Total carnitine palmitoyltransferase activity
      was increased by dietary CLA supplementation in both fat pad and skeletal muscle;
      the differences were significant for fat pad of fed mice and skeletal muscle of
      fasted mice. In cultured 3T3-L1 adipocytes CLA treatment (1 x 10(-4)M)
      significantly reduced heparin-releasable lipoprotein lipase activity (-66%) and
      the intracellular concentrations of triacylglyceride (-8%) and glycerol (-15%),
      but significantly increased free glycerol in the culture medium (+22%) compared
      to control (P < 0.05). The effects of CLA on body composition appear to be due in
      part to reduced fat deposition and increased lipolysis in adipocytes, possibly
      coupled with enhanced fatty acid oxidation in both muscle cells and adipocytes.

PMID- 9270978
TI  - Correlation of suppressed linoleic acid metabolism with the hypocholesterolemic
      action of eritadenine in rats.
AB  - The dose-dependent effects of dietary eritadenine on the metabolism of linoleic
      acid and on the plasma cholesterol concentration were investigated to clarify the
      mechanism of the hypocholesterolemic action of eritadenine in rats. Rats were fed
      control or eritadenine-supplemented (2 to 20 mg/kg) diets for 14 d. Eritadenine
      supplementation significantly decreased both the plasma cholesterol concentration
      and the 20:4n-6/18:2n-6 ratio of liver microsomal and plasma phosphatidylcholine
      (PC) in a dose-dependent manner. Eritadenine was also found to decrease the
      activity of delta 6 desaturase in liver microsomes; there was significant
      correlation between the delta 6-desaturase activity and the 20:4n-6/18:2n-6 ratio
      in the PC of liver microsomes (r = 0.989, P < 0.001) or plasma (r = 0.986, P <
      0.001). Certain plasma PC molecular species, as represented by 16:0-18.2, were
      increased by eritadenine in a dose-dependent manner, and certain plasma PC
      molecular species, as represented by 18:0-20:4, were conversely decreased by
      eritadenine. There was a significant correlation between the plasma total
      cholesterol concentration and the proportion of the sum of plasma PC molecular
      species which contain 18:1 or 18:2 in the sn-2 position. These results support
      the idea that the suppression of linoleic acid metabolism by eritadenine might be
      associated with the hypocholesterolemic action of eritadenine.

PMID- 9270979
TI  - Effect of trifluoperazine on certain arterial wall lipid-metabolizing enzymes
      inducing atherosclerosis in rhesus monkeys.
AB  - The effect of trifluoperazine (TFP) was investigated on arterial wall lipid
      metabolizing enzymes like acyl-CoA:cholesterol acyltransferase (ACAT) and
      cholesterol ester hydrolase (CEH) in rhesus monkeys. The activity was determined
      in aortic wall homogenates obtained from rhesus monkeys fed an atherogenic diet
      coupled with intramuscular injections of adrenaline and TFP. Although TFP had no
      significant effect on serum cholesterol and triglycerides, it decreased
      significantly the formation of atherosclerotic lesions by decreasing the
      esterification of cholesterol, by inhibiting ACAT and enhancing its utilization
      by activating CEH. Hence, the preventive effect of TFP on the development of
      atherosclerosis in rhesus monkeys is mediated through its ability to influence
      the activities of arterial wall lipid-metabolizing enzymes like ACAT and CEH.

PMID- 9270980
TI  - Short-term effects of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor on
      cholesterol and bile acid synthesis in humans.
AB  - Competitive inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase improve
      hypercholesterolemia. However, reports about the effects of these agents on bile
      acid synthesis, the metabolic pathway of cholesterol, are conflicting. We studied
      the short-term effect on one of these agents, pravastatin, on bile acid
      synthesis. Six male volunteers were given 40 mg of pravastatin. Plasma mevalonate
      level (which reflects cholesterol synthesis) and 7 alpha-hydroxy-4-cholesten-3
      one level (which reflects bile acid synthesis) were measured every 2 h for 8 h.
      These plasma levels were compared to those of the same volunteers without
      pravastatin. Plasma mevalonate level after 2 h was lower than control (3.0 +/-
      1.1 ng/mL vs. 6.7 +/- 2.5, mean +/- SD; P < 0.05). This decrease continued for 8
      h (2.5 +/- 0.8 vs. 5.2 +/- 1.5; P < 0.05). On the other hand, plasma 7 alpha
      hydroxy-4-cholesten-3-one level did not change until after 6 h; then at 8 h it
      was lower than control (15.7 +/- 11.8 ng/mL vs. 24.7 +/- 16.9; P < 0.05).
      According to three-way layout analysis of variance, mevalonate level was
      influenced by both pravastatin treatment (P < 0.01) and time-course (P < 0.01).
      On the other hand, the 7 alpha-hydroxy-4-cholesten-3-one level was affected by
      both individual difference (P < 0.01) and time course (P < 0.01), but pravastatin
      treatment did not influence this compound. This indicates that bile acid
      synthesis was influenced by pravastatin, although cholesterol synthesis was
      inhibited. The short-term inhibition of cholesterol synthesis did not affect bile
      acid synthesis.

PMID- 9270981
TI  - Oxidation of cholesterol in synaptosomes and mitochondria isolated from rat
      brains.
AB  - Cholesterol and alpha-tocopherol oxidations were studied in brain subcellular
      fractions isolated from cerebral hemispheres of 4-month-old, male Fischer 344
      rats. The fractions were suspended in buffered media (pH 7.4, 37 degrees C0 and
      oxidized by adding (i) ferrous iron (Fe2+) with or without ascorbate or (ii)
      peroxynitrite (an endogenous oxidant produced by the reaction of superoxide and
      nitric oxide). Treatment of subcellular fractions with Fe2+ in the presence or
      absence of ascorbate produced primarily 7-keto- and 7-hydroxy-cholesterols and
      small amounts of 5 alpha, 6 alpha-epoxycholesterol. Since brain contains high
      levels of ascorbate, and release of iron could result in oxysterol formation.
      Peroxynitrite oxidized alpha-tocopherol but not cholesterol. Hence, the toxicity
      of peroxynitrite or nitric oxide could not be due to cytotoxic oxysterols. When
      synaptosomes were incubated for 5 min in the presence of 0.5 to 2 microM Fe2+ and
      ascorbate, alpha-tocopherol was oxidized while cholesterol remained unchanged.
      Thus, alpha-tocopherol is functioning as an antioxidant, protecting cholesterol.
      Diethylenetriaminepentaacetic acid blocked production of oxysterols, whereas
      citrate, ADP and EDTA did not. A significant percentage of mitochondrial
      cholesterol was oxidized by treatment with Fe2+ and ascorbate. Hence,
      mitochondrial membrane properties dependent on cholesterol could be particularly
      susceptible to oxidation. The oxysterols formed were retained within the
      membranes of synaptosomes and mitochondria. The 7-oxysterols produced are known
      to be inhibitors of membrane enzymes and also can modify membrane permeability.
      Hence, oxysterols may plan an important role in brain tissue damage during
      oxidative stress.

PMID- 9270982
TI  - Absorption of dietary cholesterol oxidation products and incorporation into rat
      lymph chylomicrons.
AB  - Cholesterol oxidation products (oxysterols) induce macrophage lipid loading and
      accumulate in early arterial fatty streaks. The origin of lesion oxysterols has
      not been elucidated. The absorption of oxysterols from the diet and transport to
      the arterial wall by postprandial lipoprotein remnants may be a significant
      source. This study aimed to investigate the extent of oxysterol absorption and
      the effect on chylomicron composition. Cholesterol was heat-treated, causing 30%
      oxidation; the major oxidation products were 7 beta-hydroxycholesterol, 7-keto
      cholesterol, 5 alpha,6 alpha-epoxycholesterol, and 5 beta,6 beta
      epoxycholesterol. Conscious lymph-cannulated rats were given a bolus gastric
      infusion of 50 mg oxidized cholesterol or 50 mg purified cholesterol in a vehicle
      of triglyceride. In the rats given the oxidized cholesterol, 6% of the oxysterol
      load was absorbed and incorporated into lymph chylomicrons. Rats given pure
      cholesterol had no increase in oxysterols above baseline levels. The
      incorporation of oxysterols into lymph chylomicrons differed over time with 7
      beta-hydroxycholesterol, having peak absorption at 3 h, followed by 7
      ketocholesterol at 4 h and 5 alpha,6 alpha-epoxy-cholesterol at 5 h. The
      absorption of oxysterols in animals given the oxidized cholesterol gastric
      infusate was associated with lymph chylomicron compositional changes at 2-4 h.
      The oxidized cholesterol-treated group had a twofold increase in the cholesterol
      (890 +/- 84 micrograms vs. 440 +/- 83 microgram at 3 h) and triglyceride content
      (19.76 +/- 3.4 micrograms vs. 8.49 +/- 3.8 micrograms at 3 h). This led to a
      doubling of chylomicron size over this postprandial period, with particles having
      a mean diameter of 294 nm in the oxidized cholesterol-treated animals, compared
      to 179 nm in the purified cholesterol group. In conclusion, dietary oxysterols
      appear to influence postprandial lipoprotein particle size and composition. These
      changes may have effects on the clearance of chylomicrons from plasma, arterial
      delivery of oxysterols, and possible deposition in arterial lesions.

PMID- 9270984
TI  - Facile and general method for preparation of (E)-4-hydroxy-2-alkenals.
AB  - A facile one-pot synthesis of (E)-4-hydroxy-2-alkenals such as (E)-4-hydroxy-2
      nonenal, (E)-4-hydroxy-2-heptenal, and (E)-4-hydroxy-2-hexenal was achieved from
      the corresponding (2E,4E)-2,4-alkadienals by reduction-oxygenation with molecular
      oxygen and triethylsilane in the presence of cobalt(II) porphyrin as a catalyst
      followed by treatment with trimethylphosphite.

PMID- 9270983
TI  - Refeeding varying fatty acid and cholesterol diets alters phospholipids in rat
      intestinal brush border membrane.
AB  - Refeeding a diet initially given shortly after weaning results in a different
      adaptive change in the in vitro intestinal uptake of sugars and lipids than if
      the diet is given for the first time at a later age. This study was undertaken in
      rats to test the hypothesis that changes in nutrient uptake associated with
      refeeding diets containing beef tallow (S), beef tallow plus 1% cholesterol (Sc),
      fish oil (F), or fish oil plus cholesterol (Fc) are associated with changes in
      the brush border membrane (BBM) phospholipids and phospholipid fatty acids.
      Weanling Sprague-Dawley rats were fed ad libitum one of the four diets. At 35 d
      of age (about 2 wk after weaning), the rats were maintained on either the same
      diet used at weaning, or were switched to one of the other semisynthetic diets
      which were then fed for a further 7 wk. At week nine (2 + 7) the rats were either
      continued on the same diet or were switched back to the original diet for 2 wk (2
      + 7 + 2). The groups of animals which were compared included SSSc vs. ScSSc;
      ScScS vs. SScS; FFFc vs. FcFFc; and FcFcF vs. FFcF. Refeeding S, Sc, F, or Fc had
      no effect on food consumption or on body weight gain. Refeeding Fc resulted in
      increased ileal BBM total phospholipids, whereas rechallenge with F resulted in a
      decline in the jejunal BBM ratio of phospho-lipid/cholesterol. Refeeding Sc
      resulted in a decrease in the ileal BBM phosphatidylcholine (PC). In rats
      rechallenged with Fc, there was increased ileal BBM sphingomyelin (SM), increased
      ileal BBM phosphatidylethanolamine (PE), decreased ileal BBM PC/PE, and an
      increased ileal BBM SM/PC. Refeeding had no effect on the fatty acyl constituents
      of the jejunal of ileal BBM PC or PE. These results suggest that there are late
      effects of the early introduction of dietary cholesterol on intestinal BBM
      phospholipid content and composition that may contribute to the previously
      reported changes in intestinal nutrient absorption.

PMID- 9270985
TI  - Lipase-catalyzed monoesterification of 1-O-hexadecylglycerol in organic solvents.
AB  - A simple method is presented to esterify 1-O-hexadecyl-rac-glycerol using lipases
      in different organic solvents. The following fatty acids were used: C14:0, C16:0,
      C18:0, C18:1, and C18:2. Monoesterification was achieved by using a limiting
      amount of fatty acid. Both the 1-O-hexadecyl-3-O-acylglycerol and the 2-O
      acylglycerol were obtained in a total yield of 75% and a ratio 7:1 in
      dichloromethane after 3 d. Chromatographic data for the monoesters, useful for
      the identification of the natural products, are given (gas-liquid chromatography,
      thin-layer chromatography, reverse-phase thin-layer chromatography). The
      structure was confirmed by a chemical synthesis of 1-O-hexadecyl-2-O
      hexadecanoylglycerol. The 3-O-glyceride was also formed by acyl migration, as the
      minor component. The monoesters were separated by column chromatography and
      characterized by 1H and 13C nuclear magnetic resonance spectra.

PMID- 9270986
TI  - Beta 2-agonist-elevated stress response in human bronchial epithelial cells in
      vivo and in vitro.
AB  - Recent studies report high baseline levels of stress (heat shock) proteins in
      bronchial epithelial cells from asthmatic individuals. The promoter of the gene
      encoding the 72-kDa heat shock protein has an element responsive to cAMP, which
      may be affected by beta-agonists. This study examined stress protein levels in
      subjects enrolled in a segmental lung allergen challenge study to determine
      whether beta-agonist medication could contribute to a stress response. Subjects
      were divided on the basis of no premedication (n = 17), metered dose inhalations
      of albuterol (n = 24), or placebo inhalation (n = 3) prior to bronchoscopy.
      Levels of the inducible stress protein Hsp72 and constitutive Hsp73 were
      quantitated in bronchial epithelial cells from brush biopsy of allergic
      nonasthmatic, allergic asthmatic, and normal individuals. Mean levels were
      increased significantly (p < 0.003 and p < 0.004, respectively) in those subjects
      who received albuterol premedication. No significant differences were found
      between clinical groups of individuals or for placebo inhalation vs
      nonpremedication. Albuterol in vitro increased the levels of Hsp72 and Hsp73 in
      epithelial cells from either nonpremedicated or placebo-treated donors; the Hsp72
      levels correlated linearly with increased albuterol concentration (r = 0.81, p <
      0.01). Therefore, beta-agonists elevate or prolong an elevated stress response in
      epithelial cells, possibly through cAMP-mediated effects.

PMID- 9270987
TI  - Short-term effects of bracing on exercise performance in mild idiopathic thoracic
      scoliosis.
AB  - In adolescent idiopathic thoracic scoliosis (ITS) working capacity may be reduced
      during exercise. Despite concern about its usefulness, bracing is still being
      used in ITS. Thus the effects of bracing on exercise performance need to be
      examined. We studied six females, ages 12-15 years who had mild ITS (Cobb angle
      range 20-35 degrees). Pulmonary volumes, maximal voluntary ventilation (MVV),
      breathing pattern, the lowest (most negative in sign) pleural pressure during
      sniff maneuver (Pplsn), and pleural pressure swings (Pplsw) were measured first.
      Then, Pplsw, O2 uptake (VO2), CO2 output (VCO2), heart rate (HR) at rest and
      during progressive incremental exercise on a cycling ergometer (10 watts/min)
      were recorded. The exercise test was performed under control conditions without
      bracing (C) and after 7 days of bracing with the braced on (B). Dyspnea was
      measured by a modified Borg scale. At rest, bracing mildly affected total lung
      capacity and forced vital capacity (p < 0.03 for both) but not breathing pattern,
      Pplsn, or Pplsw (%Pplsn), a measure of respiratory effort. Furthermore, bracing
      did not consistently affect maximum work rate (WRmax). In both B and C VO2 was
      below (< 70%) the predicted value, VE was below (< 45%) MVV, and HR reserve was <
      15 beats/min, indicating some cardiovascular deconditioning. On the other hand,
      respiratory frequency (Rf) increased more in B than in C (p < 0.03). In addition,
      Pplsw, Pplsw (%Pplsn), and Pplsw (%Pplsn)/VT, an index of neuroventilatory
      dissociation (NVD) of the respiratory pump, were greater in B (p < 0.03 for all).
      At a similar work rate, the Borg rating score was greater with bracing on than
      off, and the difference (delta Borg) tended to relate to concurrent changes in
      Pplsw (%Pplsn)/VT (r2 = 0.71; p < 0.07). We conclude that bracing affects
      respiratory effort, NVD, and dyspnea score during progressive exercise. These
      effects are consistent with increased lung elastance. Diminished exercise
      tolerance in patients with mild ITS probably reflects impaired physical fitness
      but is not affected by bracing. Training programs proposed for this subset of
      patients to increase peripheral muscle performance might also consider NVD of the
      respiratory pump.

PMID- 9270988
TI  - Chronic exertional dyspnea and respiratory muscle function in patients with
      chronic obstructive pulmonary disease.
AB  - The symptom of breathlessness is an important outcome measure in the management
      of patients with chronic obstructive pulmonary disease (COPD). Clinical ratings
      of dyspnea and routine lung function are weakly related to each other. However,
      in the clinical setting breathlessness in COPD is encountered under conditions of
      increased respiratory effort, impeded respiratory muscle action, or functional
      weakness. Thus, the present study was carried out to determine whether and to
      what extent clinical ratings of dyspnea and respiratory muscle dysfunction relate
      to each other. In 21 patients with COPD two methods were used to rate dyspnea: a
      modified Medical Research Council Scale (MRC) and the Baseline Dyspnea Index
      (BDI), which is a multidimensional instrument for measuring dyspnea based on
      three components: magnitude of task, magnitude of effort, and functional
      impairment. A baseline focal score was obtained as the sum of the three
      components. Measures were: pulmonary volumes; arterial blood gases; maximal
      voluntary ventilation (MVV); maximal inspiratory and expiratory pressures (MIP
      and MEP, respectively); and breathing patterns ventilation (VE), tidal volume
      (VT), and respiratory frequency (Rf). In 15 patients pleural pressure was also
      measured during both quiet breathing (Pplsw) and maximal inspiratory sniff
      maneuver at FRC (Pplsn). BDI and MRC ratings related to each other and showed
      comparable weak associations with standard parameters (FEV1, PaCO2, VT), MIP, and
      MEP. In contrast, MVV closely and similarly related to both ratings. Pplsw
      (%Pplsn), a measure of respiratory effort, and Pplsw (%Pplsn)/VT(%VC), an index
      of neuroventilatory dissociation, related significantly to both the BDI (r2 = 
      0.77 and r2 = -0.75, respectively) and the MRC (r2 = 0.81 and r2 = 0.74,
      respectively). Using MVV, Pplsw (%Pplsn), and Pplsw (%Pplsn)/VT(%VC) in a
      stepwise multiple regression as independent variables with BDI rating as
      dependent variable, MVV explained an additional 14.5% of the variance of the BDI
      over the 67.8% predicted by Pplsw (%Pplsn). Our results demonstrate that the
      level of chronic exertional dyspnea in COPD increases as the ventilatory muscle
      derangement increases. The level of the relationships among dyspnea ratings and
      MVV and respiratory effort helps to explain some of the mechanisms of chronic
      dyspnea of COPD. These measures should be considered for therapeutic intervention
      to reduce dyspnea.

PMID- 9270989
TI  - Decreased selenium concentration and glutathione peroxidase activity in blood and
      increase of these parameters in malignant tissue of lung cancer patients.
AB  - We studied the selenium (Se) concentration in whole blood and plasma, glutathione
      peroxidase (GSH-Px) activity in red blood cells and plasma, as well as both of
      these parameters in cancerous and tumor-free lung tissue of lung cancer patients.
      Blood samples were taken from 84 cancer patients and 61 healthy controls. Normal
      and neoplastic lung tissues were obtained from 57 patients at the time of
      surgery. Se concentrations in whole blood and plasma were lower by 23% (p <
      0.001) in patients compared with controls. GSH-Px activity in red cells was lower
      by 20.2% (p < 0.004) and in plasma by 11.7% (p < 0.05) in patients than in the
      control group. On the other hand, the tumor Se level was higher by 66.6% (p <
      0.0001) and GSH Px activity by 49.5% (p < 0.0001) than in adjacent tumor-free
      tissue. No differences in Se concentrations and GSH-Px activities were found
      between squamous cell carcinoma and adenocarcinoma nor among the clinical stages
      of the disease. In the whole blood and plasma of cancer patients significantly
      lower Se concentrations were found in smokers than in nonsmokers. Significantly
      lower Se concentrations were also found among cancer patients who were smokers
      compared with controls. These findings show that in the blood of cancer the
      antioxidant ability, as measured by Se and GSH-Px, is reduced significantly. The
      cause of increased Se and GSH-Px in the malignant part of the lung is not
      understood and requires further studies.

PMID- 9270990
TI  - Effects of GABA-B agonist baclofen on bronchial hyperreactivity to inhaled
      histamine in subjects with cervical spinal cord injury.
AB  - Bronchial provocation studies performed in our research center have consistently
      demonstrated airway hyperresponsiveness to both inhaled methacholine and
      histamine in subjects with chronic cervical spinal cord injury (SCI). More
      recently, we reported that the airways of such subjects maintained on chronic
      baclofen (gamma-aminobutyric acid) therapy were not hyperreactive to inhaled
      methacholine. In this study we determined whether baclofen also blocks the
      effects of the bronchoprovocative agent histamine in subjects with cervical SCI.
      Twenty-four male subjects with cervical SCI participated in this study; 14 were
      maintained on oral baclofen, and 10 served as age-matched controls. The subjects
      were challenged with increasing concentrations of aerosolized histamine until
      either a 20% fall in forced expiratory volume in 1 s (FEV1) from baseline
      (defined as PC20) was observed, or a maximum of 25 mg/ml histamine was
      administered. We found that 11 of the 14 baclofen subjects (78.5%) and 8 of the
      10 control subjects (80%) responded (PC20 < 8 mg/ml) to the histamine challenge.
      Mean PC20 values among responders in the baclofen (PC20 = 2.91 +/- 2.3) and
      control (PC20 = 2.18 +/- 1.9) groups did not differ significantly. Because
      histamine acts directly on histamine receptors and indirectly on cholinergic
      pathways, our findings that baclofen blocks bronchoconstriction due to inhaled
      methacholine, but not that due to histamine, suggests that hyperresponsiveness in
      subjects with cervical SCI may be secondary to nonspecific airway
      hyperreactivity.

PMID- 9270991
TI  - Invasive pneumococcal disease in the immunocompromised host.
AB  - A normal constituent of the human upper respiratory flora, Streptococcus
      pneumoniae also produces respiratory tract infections that progress to invasive
      disease at high rates in specific risk groups. The individual factors that
      contribute to the development of invasive pneumococcal disease in this distinct
      minority of persons, include immune (both specific and innate), genetic, and
      environmental elements. Specific defects in host responses may involve age,
      deficiencies in levels of antibodies and complement factors, and splenic
      dysfunction. Combinations of these immune defects contribute to the increased
      rates of invasive pneumococcal disease in patients with sickle cell disease,
      nephrotic syndrome, neoplasms, and underlying medical conditions such as diabetes
      and alcoholic liver disease. The number of risk factors are greatest and the
      rates of invasive disease are highest in patients with HIV-1 infection, which has
      emerged as a major risk factor for serious S. pneumoniae infection worldwide.

PMID- 9270992
TI  - Control of recombination rate during transformation of Streptococcus pneumoniae:
      an overview.
AB  - Despite the fact that natural transformation was described long ago in
      Streptococcus pneumoniae, only a limited number of recombination genes have been
      identified. Two of them have recently been characterized at the molecular level,
      recA which encodes a protein essential for homologous recombination and mmsA
      which encodes the homologue of the Escherichia coli RecG protein. After a survey
      of the available information regarding the function of RecA, RecG, and other
      proteins such as the mismatch repair proteins HexA and HexB that can affect the
      outcome of recombinants, the different levels at which horizontal genetic
      exchange can be controlled are discussed. It is shown that the specific induction
      of the recA gene which occurs in competent cells is required for full
      recombination proficiency. Results regarding the ability of the Hex generalized
      mismatch repair system to prevent recombination between partially divergent
      sequences during transformation are also summarized. A structural analysis of
      homeologous recombinants which suggests that formation of mosaic recombinants can
      occur independently of mismatch repair in a single-step transformation is also
      reported. Finally, arguments in favor of an evolutionary origin of transformation
      as a means of genome evolution are discussed and the different types of
      recombination events observed which could potentially contribute to S. pneumoniae
      genome evolution are listed.

PMID- 9270993
TI  - Molecular epidemiology of drug-resistant pneumococci: toward an international
      approach.
AB  - An international multicenter study was undertaken to investigate the
      epidemiological dynamics of penicillin-resistant pneumococci. We compared the
      molecular epidemiological characteristics of 205 penicillin-resistant isolates
      originating from The Netherlands, Thailand, United States, Spain, Greece, Poland,
      Cuba, Germany, Finland, United Kingdom, South Africa, Hungary, Portugal, Croatia,
      and the Czech Republic. Eighty-four distinct restriction fragment end labeling
      (RFEL) types were observed. Twenty-eight genetic types were shared by two or more
      strains. Five genetic clusters consisted of strains originating from different
      countries, illustrating dissemination of penicillin-resistant pneumococci among
      countries. The strains displaying the two predominant RFEL types corresponding
      with the pandemic clones 23F and 9V were found in 10 and 6 different countries,
      respectively. This clearly demonstrates the pandemic behavior of these two
      clones. Twelve out of the 28 genetic clusters contained two or more serotypes.
      This finding indicates frequent horizontal transfer of capsular genes. Within
      distinct RFEL types, identical penicillin binding protein (PBP) genotypes were
      often observed, suggesting a high frequency of horizontal transfer of penicillin
      resistance genes. The most predominant PBP type was found in 15 distinct RFEL
      types, comprised 44% of the entire collection, and was observed in 11 countries.
      The vast majority of the strains belonging to the pandemic clones 23F and 9V
      shared this predominant PBP type. We hypothesize that the clones 23F and 9V are
      responsible for the worldwide increase of penicillin-resistance, because they
      serve as a genetic reservoir for susceptible pneumococci to acquire penicillin
      resistance.

PMID- 9270994
TI  - Spread of the Spanish multi-resistant serotype 23F clone of Streptococcus
      pneumoniae to Seoul, Korea.
AB  - Multi-resistant serotype 23F pneumococcal strains from an outbreak in a day-care
      centre in South Africa and strains from sporadic cases in Korea were analysed for
      their relatedness, by means of arbitrarily-primed PCR (AP-PCR), repetitive
      extragenic palindromic PCR (rep-PCR) and penicillin-binding protein (PBP) gene
      profiles. The South African strains previously shown to be identical to the 23F
      Spanish clone had identical AP-PCR and rep-PCR patterns to 13 Korean isolates.
      PBP gene analysis of strains from this cluster showed identical fingerprints,
      suggesting clonality. Isolates, identical genotypically to the 23F clone appeared
      to have acquired the type 19F and 14 capsular serotypes, respectively, a result
      that suggests horizontal transfer of capsular biosynthetic genes. These same
      techniques revealed three serotype 9V isolates not closely related to the 23F
      clone but which harbour PBP genes identical to the 23F clone. The data presented
      suggests that a clone of S. pneumoniae serotype 23F related to isolates from
      Spain and South Africa has become disseminated in Korea.

PMID- 9270995
TI  - Molecular characterization of a mutation affecting the amount of Streptococcus
      pneumoniae penicillin-binding protein 3.
AB  - We have studied the molecular structure of the gene for the penicillin binding
      protein (PBP 3) of the Streptococcus pneumoniae wild-type strain and a laboratory
      mutant strain that exhibits a reduced amount of this protein on PBP gels. This
      mutation affects cefotaxime resistance when transferred into resistant strains.
      We have sequenced the PBP3 gene, dacA, and upstream regions from the wild-type
      isogenic strain and the laboratory mutant. We show that a deletion of one base
      pair in the upstream sequence of this gene account for the phenotype by
      decreasing the amount of PBP3.

PMID- 9270996
TI  - Increase in multiple antibiotic resistance in nontyphoidal salmonellas from
      humans in England and Wales: a comparison of data for 1994 and 1996.
AB  - The incidence of multiple drug resistance (to four or more antimicrobials) in
      salmonellas from humans in England and Wales in 1996 has been compared with
      corresponding data for 1994. For Salmonella enteritidis multiple resistance has
      remained rare, although a high proportion of isolates of phage type 6A have shown
      resistance to ampicillin. For S. typhimurium multiple resistance has continued to
      increase, with 81% of isolates now multiresistant. Of particular importance in S.
      typhimurium has been the continued epidemic of multiresistant DT 104 and the
      increasing occurrence of strains of this phage type with additional resistance to
      trimethoprim and/or ciprofloxacin. For S. virchow, a 10% increase in multiple
      resistance is mainly concentrated in two phage types common in returning
      travellers. For S. hadar, there has been a substantial increase in the incidence
      of multiple resistance with over 50% of isolates now multiresistant. Substantial
      increases in the incidence of resistance to ciprofloxacin in multiresistant S.
      typhimurium DT 104, S. virchow, and S. hadar since 1993, when the fluoroquinolone
      antibiotic enrofloxacin was licensed for veterinary use in the UK, are of
      particular concern.

PMID- 9270997
TI  - Antibiotic-resistant Vibrio cholerae in Parangipettai coastal environs, south
      east India.
AB  - This study was undertaken to determine the comparative incidence of drug
      resistant Vibrio cholerae non-01 in the environmental samples (water, sediment,
      and plankton) and in the seafood samples (finfish, shellfish, and crustacean) of
      estuarine, coastal, and mangrove communities. A total of 770 V. cholerae isolates
      were examined--all of the strains were sensitive to 100% against cephalothin (30
      mcg), chloramphenical (30 mcg), and polymyxin-B (300 mcg). However, all of the
      strains isolated form environmental and seafood samples showed higher resistance
      (> 25%) to oxytetracycline, streptomycin, sulphadiazine, tetracycline, and to
      streptomycin, sulphadiazine, and tetracycline, respectively. The percentage of
      strains resistant to other antimicrobial substances depended on the antibiotic
      and on the isolation source. Among the isolates tested, a significantly higher
      number of drug-resistant bacteria was found to occur in water and finfish
      samples.

PMID- 9270998
TI  - Studies on the distribution of high-level gentamicin-resistant Enterococcus
      faecalis using ribotyping and restriction analysis of the 16S-23S rRNA intergenic
      spacer sequences.
AB  - Twenty-five high-level gentamicin resistant (HLGR) Enterococcus faecalis strains
      were isolated from three different University laboratories in Italy. The
      resistant strains were variously distributed in the three centers with
      percentages of prevalence ranging from about 3% up to 14%. Almost all strains
      shared high-level resistance to streptomycin (23 out of 25). Ribotyping and
      restriction analysis of the 16S-23S rRNA intergenic spacer sequences were used to
      genetically differentiate the various strains and to study their spreading in the
      university hospitals serviced by the three laboratories. At least three ribotypes
      were identified, which showed a peculiar distribution in the various centers.
      Only the ribotype B was isolated from the University of Padua. In Cagliari, most
      strains belonged to ribotype A (4/6), whereas in Genoa there was an equal
      distribution of the ribotypes A and B. A clonal spreading of some HLGR strains is
      suggested by these findings. The restriction analysis of the 16S-23S rRNA
      intergenic-spacer sequences gave comparable results with classical ribotyping
      and, in addition, was quicker and easier to perform than the latter.

PMID- 9270999
TI  - Effect of Mycobacterium avium infection on the influx, accumulation, and efflux
      of KRM-1648 by human macrophages.
AB  - KRM-1648 is a new benzoxazinorifamycin with activity in vitro and in vivo against
      organisms of the Mycobacterium avium complex. We investigated the ability of 14C
      KRM-1648 to concentrate within human monocyte-derived macrophages in vitro. KRM
      1648 is rapidly taken up by uninfected macrophages, with 90% of the initial
      concentration added to the monolayer found within macrophages by 1 h and
      approximately 80% at 2 h. Comparable results were obtained in assays using
      macrophages that have been infected with an AIDS-related strain of M. avium for
      24 h. In contrast, macrophages infected with M. avium for 3 days, showed an
      impaired ability to concentrate KRM-1648, primarily because of a significant
      efflux of the antibiotic (intracellular concentration of 86% of the available
      drug was present within macrophages at 1 h vs. 47% at 2 h). Daily administrations
      of KRM-1648 to a macrophage monolayer for 3 consecutive days resulted in
      significant accumulation of the drug within phagocytic cells. Although the efflux
      was greater in M. avium-infected macrophages than in uninfected cells,
      consecutive administration of KRM-1648 led to a total intracellular accumulation
      of drug that exceeded the initial level and appeared to continue to accumulate.
      The ability of KRM-1648 to rapidly accumulate in human macrophages, including M.
      avium-infected cells, may explain, in part, the improved therapeutic
      effectiveness in animal models against M. avium and M. tuberculosis.

PMID- 9271000
TI  - Eight-year surveillance of non-albicans Candida spp. in an oncology department
      prior to and after fluconazole had been introduced into antifungal prophylaxis.
AB  - From 1989 until 1996, during the last 8 years, the proportion of Candida (C.)
      krusei, and other non-albicans Candida spp. isolated from surveillance cultures
      and from sterile body sites, was analyzed among 13,758 admissions in a National
      Cancer Institute. During these admissions a total of 9,042 isolates were
      prospectively collected from surveillance cultures, and 126 from blood cultures.
      The proportion of C. krusei among all organisms was 12.7% to 16.5% in 1989
      through 1991, i.e., before fluconazole was introduced into prophylactic
      protocols. After the introduction of fluconazole into prophylaxis in acute
      leukemia in 1992 the incidence of C. krusei was 7.9% to 8.6% during 1994 to 1996.
      After 5 years of using this drug for prophylaxis, the incidence of C. krusei was
      lower than before this drug was introduced in our institute. Among yeasts, the
      most frequently isolated pathogen was still Candida albicans (72.2% of all
      isolated fungal organisms). Among molds, Aspergillus spp. was the most frequently
      isolated agent. Analyzing the etiology of proven fungal infections (fungemias)
      confirmed by positive blood cultures, C. albicans was the most common causative
      organism in 53.8% of cases. The incidence of fungemia due to Torulopsis (C.)
      glabrata and C. krusei before and after fluconazole introduction did not change.
      Of 126 organisms isolated from blood cultures, there was no increase in T. (C.)
      glabrata or C. krusei after introduction of fluconazole for prophylaxis and
      therapy, and the quoted 6.4% of fungemic episodes remained stable with an
      incidence of 1 fungemia/year since 1991. The proportion of C. krusei and C.
      glabrata among Candida spp. was decreasing in our center between 1989 and 1996.
      Also, the proportion of non-albicans Candida spp. among isolates decreased from
      25.7% in 1990 to 11.9% in 1996.

PMID- 9271001
TI  - Progesterone protects against lipid peroxidation following traumatic brain injury
      in rats.
AB  - The gonadal hormone, progesterone, has been shown to have neuroprotective effects
      in injured nervous system, including the severity of postinjury cerebral edema.
      Progesterone's attenuation of edema is accompanied by a sparing of neurons from
      secondary neuronal death and with improvements in cognitive outcome. In addition,
      we recently reported that postinjury blood-brain barrier (BBB) leakage, as
      measured by albumin immunostaining, was significantly lower in progesterone
      treated than in nontreated rats, supporting a possible protective action of
      progesterone on the BBB. Because lipid membrane peroxidation is a major
      contributor to BBB breakdown, we hypothesized that progesterone limits this free
      radical-induced damage. An antioxidant action, neuroprotective in itself, would
      also account for progesterone's effects on the BBB, edema, and cell survival
      after traumatic brain injury. To test progesterone's possible antiperoxidation
      effect, we compared brain levels of 8-isoprostaglandin F2 alpha (8-isoPGF2
      alpha), a marker of lipid peroxidation, 24, 48, and 72 h after cortical contusion
      in male rats treated with either progesterone or the oil vehicle. The brains of
      progesterone treated rats contained approximately one-third of the 8-isoPGF2
      alpha found in oil-treated rats. These data suggest progesterone has antioxidant
      effects and support its potential as a treatment for brain injury.

PMID- 9271003
TI  - Effects of halothane, alpha-chloralose, and pCO2 on injury volume and CSF beta
      endorphin levels in focal cerebral ischemia.
AB  - Anesthetic agent, arterial pCO2 level, and opioid peptides have all been
      implicated in the pathophysiology of experimental stroke models. The effects of
      halothane, alpha-chloralose, and differing concentrations of arterial pCO2 on
      injury volume and CSF beta-endorphin levels were studied in a feline model of
      experimental focal cerebral ischemia. The type of anesthetic agent used had no
      effect on injury volume following 6 h of focal cerebral ischemia. Over a 6-h
      period, beta-endorphin levels significantly increased from 10.1 +/- 5.0 fmol/mL
      at zero time to 14.4 +/- 7.2 fmol/mL at 6 h under halothane anesthesia (p <
      0.05), whereas they did not significantly change (10.1 +/- 6.7 to 7.8 +/- 4.7
      fmol/mL) under alpha-chloralose anesthesia. In contrast, hypercapnia had no
      effect on beta-endorphin levels, but significantly increased injury volume from
      30.6 +/- 5.7% of the ipsilateral hemisphere under normocapnic conditions to 37.1
      +/- 5.9% under hypercapnic conditions (p < 0.05). These results suggest that
      hypercapnia increases injury volume in a feline model of focal cerebral ischemia,
      and pCO2 should be controlled in experimental focal cerebral ischemia models.

PMID- 9271002
TI  - Effects of cadmium, copper, and zinc and beta APP processing and turnover in COS
      7 and PC12 cells. Relationship to Alzheimer disease pathology.
AB  - The effects of cadmium, copper, and zinc on beta APP metabolism were investigated
      in COS-7 and PC12 cells. Cadmium chloride (CdCl2) increased beta APP steady-state
      protein levels and decreased beta APP posttranslational processing. These changes
      were not accompanied by alterations in beta APP mRNA levels or splicing. In
      addition, cytosolic alpha-actin and G3PDH levels were not affected. Further,
      neither zinc (ZnCl2) nor copper (CuSO4) altered beta APP levels or affected its
      normal processing. Pulse-chase studies revealed that the rate of beta APP
      maturation decreased twofold in the presence of 25 microM CdCl2 compared to
      untreated controls. beta APP secretion from the cell also dramatically slowed.
      These two factors result in the accumulation of partially processed beta APP
      inside cells. The presence of CdCl2 also decreased the amount of an 8-kDa beta
      APP C-terminal fragment, indicating that the cellular compartment in which beta
      APP accumulates is not accessible to alpha-secretase. Studies using Brefeldin A
      suggest that this compartment may be the cis or medial Golgi. However, A beta
      production was proportionately increased. These data show that CdCl2 can modulate
      the beta APP cleavage to favor A beta. Finally, beta APP mis- metabolism was
      shown to be unrelated to the hsp70 induction elicited by CdCl2; both heat shock
      and CuSO4 induced hsp70 but had no effect on steady-state levels of beta APP,
      although heat shock did slow beta APP maturation. These data indicate that hsp70
      alone cannot chaperone beta APP through an alternate processing pathway leading
      to A beta production.

PMID- 9271004
TI  - Indirect quenching fluororeceptor assay of anti-AChR antibodies.
AB  - A fluororeceptor assay (FRA) has been developed for the determination of
      antibodies against acetylcholine receptor (AChR), employing an antifluorescein
      serum and fluorescein-labeled AChR. Antiserum raised against rat muscle AChR in
      rabbit and the labeled AChR are incubated with antifluorescein serum at room
      temperature. At high levels of anti-AChR, binding of the labeled AChR prevented
      subsequent binding of the fluorescein groups by antifluorescein, resulting in
      little change in the signals of the label. Conversely, at low levels of anti
      AChR, the free fraction of the labeled AChR is available to be bound by
      antifluorescein, which markedly reduced fluorescence intensity of the label.
      Thus, the fluorescence intensity of the assay mixture directly reflects the
      amount of anti-AChR antibodies in the serum. It is concluded that the
      availability of fluorescein-labeled AChR and the antibody directed against it
      permit measurement of anti-AChR antibodies in human myasthenia. The quality of
      the assay and its preliminary clinical application have been evaluated.

PMID- 9271005
TI  - Mitochondrial membrane fluidity and oxidative damage to mitochondrial DNA in aged
      and AD human brain.
AB  - Oxidative damage on biological molecules has been proposed as a major cause of
      alterations observed in aging brain as well as in neurodegenerative diseases. In
      this study, we measured membrane fluidity in mitochondria extracted from three
      cerebral regions and cerebellum of Alzheimer disease (AD) patients and age
      matched controls by means of fluorescence polarization technique. A significant
      reduction of mitochondrial membrane fluidity was found in AD, except in
      cerebellum. In controls, a decrease of membrane fluidity was observed along with
      age, and it was also related to the content of the oxidized nucleoside 8-hydroxy
      2'-deoxyguanosine (OH8dG) in mitochondrial DNA (mtDNA). Alteration in membrane
      fluidity seems to be a result of lipid peroxidation, since it dramatically
      decreased when mitochondria were exposed to FeCl2 and H2O2. The parallel increase
      of viscosity in mitochondrial membrane and the amount of OH8dG in mtDNA is
      suggestive of a relationship between these biological markers of oxidative
      stress. These results provide further evidence that oxidative stress may play a
      role in the pathogenesis of AD.

PMID- 9271006
TI  - Lithium prevents ouabain-induced behavioral changes. Toward an animal model for
      manic depression.
AB  - Both mania and bipolar depression have been associated with decrements in the
      activity of the sodium and potassium-activated adenosine triphosphatase (Na,K
      ATPase) membrane pump. Although the role of this observation in the
      pathophysiology of bipolar illness is unclear, it has been proposed that this
      defect could be central to the pathogenesis of the illness. In an effort to test
      this hypothesis, the authors examined the efficacy of lithium pretreatment in
      attenuating behavioral changes secondary to acute administration of a single
      intracerebroventricular (i.c.v.) dose of the Na,K-ATPase-inhibiting compound,
      ouabain, in the Sprague-Dawley rat. Ouabain (10(-3)M) significantly decreased
      motor activity in automated activity monitors. Lithium pretreatment for 7 d
      totally prevented this effect. These preliminary data suggest that i.c.v. ouabain
      administration in the rat may prove to be a viable animal model for bipolar
      illness.

PMID- 9271007
TI  - Pharmacokinetics of intracerebroventricular tBuOOH in young adult and mature
      mice.
AB  - This in vivo study compared the pharmacokinetics of intracerebroventricularly
      administered tertiary butylhydroperoxide (tBuOOH) (109.7 mg/kg) among six
      different brain regions in two age groups of mice (2- and 8-mo-old mice). Brains
      were dissected at 11 time-points ranging from 0.5-60 min. Pharmacokinetics
      parameters did not differ between the two age groups. This demonstrates that
      previously reported age-related differences in tBuOOH toxicity may not be owing
      to pharmacokinetic differences between the two age groups. Differences were found
      when comparing the pharmacokinetics of tBuOOH among the various brain regions.
      Area under the curve (AUC) values were highest in the striatum and thalamus, and
      lowest in the cerebellum. The half-life of tBuOOH varied widely among the regions
      with the longest half-lives in the cortex and hippocampus, and the shortest in
      the striatum and cerebellum. The oxidation of glutathione and the induction of
      DNA damage are critical aspects of tBuOOH toxicity. These data show that region
      dependent differences in toxicity reported previously may result from factors,
      such as tBuOOH-induced glutathione oxidation and DNA damage.

PMID- 9271008
TI  - Occurrence of myelin-associated glycoprotein (MAG)-like immunoreactivity in some
      nervous, endocrine, and immune-related cells of the rat. An immunohistochemical
      study.
AB  - The occurrence and distribution of myelin-associated glycoprotein (MAG)-like
      immunoreactivity was investigated in the rat using a polyclonal antibody to MAG
      purified from rat brain. In the nervous system, MAG immunoreactivity was found in
      the periaxonal portion of the myelinated fibers and in a small number of
      oligodendroglia in the cortex, hippocampus, and the spinal cord. The sheath of
      Schwann cells in unmyelinated fibers and satellite cells in the spinal ganglia
      were also immunoreactive for MAG. In the endocrine system, the noradrenaline
      containing cells in the adrenal medulla and some endocrine cells in the duodenum
      showed MAG immunoreactivity. In the immune system, numerous reticular cells with
      slender cytoplasmic processes, which formed a dense network, were immunopositive
      for MAG within the germinal center in the lymph nodes and spleen. In the thymus,
      a number of epithelial reticular cells within the medulla showed variation in
      staining intensity. These findings provide new information on the wide
      distribution of MAG immunoreactivity in the nervous, endocrine, and immune
      systems, and may contribute to the further understanding of the biological roles
      of this protein.

PMID- 9271009
TI  - Epidermal growth factor receptor immunoreactivity in human laryngeal squamous
      cell carcinoma.
AB  - Epidermal growth factor receptor (EGFR) is a transmembrane protein receptor with
      tyrosine kinase activity. The protein has cysteine-rich sequence repeats in its
      extracellular ligand-binding domains. Elevated levels of EGFR are associated with
      malignant transformation of squamous cells and are observed in squamous cell
      carcinomas from the lung, head, neck, skin, cervix and esophagus. We examined the
      expression of EGFR in laryngeal squamous cell carcinoma (SCC) (N = 24) and non
      neoplastic polyps (N = 7) using streptavidin-biotin immunohistochemistry and a
      monoclonal antibody (Serotec: MCA-571) to the EGFR protein. The carcinomas were
      classified as well differentiated (N = 2), moderately differentiated (N = 16) and
      poorly differentiated (N = 6). Tissues from metastatic tumor deposits in lymph
      nodes (N = 5) were also studied. Overexpression of EGFR was present, in the form
      of strong cytoplasmic immunostaining, in the majority of the SCC cases (n = 20;
      83%) and in all of the metastatic tumor deposits. In contrast, although some of
      the vocal cord polyps showed weak (n = 2) to moderate (n = 5) immunoreactivity,
      none had evidence of strong EGFR immunoreactivity. The differences in EGFR
      immunoreactivity were significant between primary laryngeal SCC and vocal cord
      polyps (p = 0.0001; chi 2 test), and between metastatic laryngeal SCC and vocal
      cord polyps (p = 0.0001; chi 2 test). Laryngeal carcinoma cases which showed EGFR
      overexpression had a lower median survival period compared to those without
      overexpression In conclusion, a different extent of EGFR expression is
      demonstrated in laryngeal squamous cell carcinomas and non-neoplastic vocal cord
      polyps using an immunohistochemical method. Some trends in the prognostic value
      of EGFR immunoreactivity in laryngeal carcinomas appear to emerge in this study.

PMID- 9271010
TI  - Aneuploidy in sclerosing adenosis may predict an increased risk of malignancy. A
      study using the AgNOR silver stain.
AB  - Sclerosing adenosis (SA) of the breast if a disease associated with an increase
      relative risk of malignancy. The exact incidence and factors influencing
      malignant transformation in association with SA are not well established. Two
      counts of the AgNOR silver staining technique have been correlated with ploidy
      and proliferative activity. The first count which is the mean number of AgNOR
      granules (mAgNOR), correlates with ploidy. The second count is the percentage of
      nuclei exhibiting > or = 5 AgNORs/nucleus (pAgNOR) and reflects proliferative
      activity. The hypothesis in the current study was that aneuploidy, as determined
      by the AgNOR silver staining technique, may potentially identify lesions of SA
      with an increased association with malignant breast disease. The AgNOR silver
      staining technique was performed on 69 cases of SA with the application of the
      two counts. Of these cases 53 were not associated with malignancy and 16 were
      associated with synchronous or metachronous carcinoma of the breast, these being
      11 cases of invasive ductal carcinoma (IDC), four cases of ductal carcinoma in
      situ (DCIS) and one case of lobular carcinoma in situ (LCIS). The patient ages
      ranged from 27 to 84 years (median 53 years) with a median follow up of 28
      months. Six of the 53 cases of SA no associated with malignancy (11%) had
      aneuploid mAgNOR counts of > or = 2.4 whereas 12 of the 16 cases associated with
      carcinoma (80%) had such counts (p < 0.0005). This included nine cases of IDC,
      two cases of DCIS and the case of LCIS. Of the six aneuploid cases not associated
      with malignancy, two cases showed cytological atypia, one case was associated
      with atypical ductal hyperplasia and one case was seen in a leukemic patient who
      had received chemotherapy and radiation therapy. The pAgNOR counts showed a
      statistically less significant correlation with malignancy (p < 0.03). These
      findings suggest that aneuploidy, measured by the AgNOR silver stein, seen in SA
      may help identify lesions with a higher relative risk of being associated with
      breast carcinoma and hence that may require more aggressive management than
      diploid ones.

PMID- 9271011
TI  - Actinic granuloma in association with giant cell arteritis: are both caused by
      sunlight?
AB  - Two cases of actinic granuloma of the skin occurring in association with a giant
      cell arteritis are reported. This is the first time that this association has
      been documented.

PMID- 9271012
TI  - Clinicopathological pattern of pulmonary thromboembolism in Chinese autopsy
      patients: comparison with Caucasian series.
AB  - The clinicopathological data of adult Chinese patients identified to have
      'significant pulmonary thromboembolism (PTE)' at autopsy in Queen Mary Hospital
      (QMH) Hong Kong, from 1990 to 1994 inclusive, were analysed retrospectively. The
      prevalence of PTE was documented and data were compared with published series of
      Caucasian patients. The parameters studied included sex-age distribution,
      associated diseases, symptomatology, site of venous thrombosis, duration of
      admission and intervals between surgery and death. The rate of PTE was 4.7% (4.5%
      in males and 5.2% in females). The mean age of PTE patients was significantly
      higher than that of non-PTE patients (p < 0.001). Two clinicopathological
      features worthy of note are: (1) as in Caucasian patients, most Chinese patients
      with 'significant PTE' do not present with leg symptoms although many of them are
      found to have deep vein thrombosis (DVT) at postmortem; and (2) DVT in these
      patients is found in the calf veins rather than in the more proximal deep veins.
      The recently identified racial differences in hemostasis that may contribute to
      the differences between Chinese and Caucasian people are discussed.

PMID- 9271013
TI  - Benign epithelial structures on the surface of appendices.
AB  - Reported here are five cases of rare and hitherto unreported adenomatoid
      epithelial structures which occurred under the peritoneal surface of appendix
      vermiformis. These epithelial structures consisted of mature, small non
      branching, cystically dilated adenomatoid spaces lined by one or two layers of
      flat cells without atypia or mitoses. In two cases these structures underwent
      focal squamous cell metaplasia. It is hypothesized that these epithelial
      structures arise from the peritoneum. They should be especially distinguished
      from metastatic adenocarcinoma.

PMID- 9271014
TI  - Inflammatory pseudotumor of the breast.
AB  - Inflammatory pseudotumors (IP) have come to the forefront in recent times with
      this characteristic lesion being described in several sites. The multiplicity of
      sites of occurrence is matched by the plethora of names given to this condition.
      It has been rejoiced under the rubric of plasma cell granuloma, xanthomatous
      pseudotumor, xanthogranuloma, inflammatory myofibroblastic tumor/lesion and
      inflammatory fibromyxoid tumor, to name but some. This paper presents three cases
      of IP occurring in the breast and highlights the histological features in this
      unusual site.

PMID- 9271015
TI  - A high apoptotic index occurs in subtypes of endometrial adenocarcinoma
      associated with a poor prognosis.
AB  - A study was carried out to determine the apoptotic index (AI) in cases of
      endometrial adenocarcinoma that are usually associated with a poor prognosis, and
      to identify in the AI in these cases differs from the AI's in grade I and II
      endometrial adenocarcinoma. The apoptotic index (defined as the percentage of
      morphologically identified apoptotic cells and apoptotic bodies in counting 3000
      tumor cells) was calculated for five grade III endometrial adenocarcinomas of no
      specific type (NST), five clear cell adenocarcinomas (CCC), three high grade
      uterine papillary serous carcinomas (UPSC) and one undifferentiated carcinoma of
      the endometrium. Overall a higher mean AI (6.3%) was identified in these poor
      prognosis neoplasms than in 13 grade I and II endometrial adenocarcinomas (mean
      AI 2.7% p < 0.0001). The apoptotic index was highest in the undifferentiated
      carcinoma (AI = 9.7%). The mean AI for the cases of UPSC, CCC and grade III
      endometrioid (NST) adenocarcinomas were 7.4%, 5.9% and 5.2% respectively. There
      was no evidence of a statistically significant difference in the AI in these poor
      prognosis groups (Kruskall Wallis test p = 0.45). Although the results show that
      a high AI is a feature of poor prognosis endometrial carcinoma, no distinction in
      AI was demonstrated in the subtypes examined.

PMID- 9271016
TI  - Test and teach. Number eighty four. Pseudomyxoma ovarii.

PMID- 9271017
TI  - Test and teach. Number eighty five. Extraneural perineurioma.

PMID- 9271018
TI  - The effect of enteric bacterial toxins on the catecholamine levels of the rabbit.
AB  - The rabbit catecholamine responses to bacterial toxins commonly found in Sudden
      Infant Death Syndrome (SIDS) victims were studied as part of a proposed animal
      model for SIDS. Six bacterial toxins commonly isolated from SIDS baby feces and a
      comparison endotoxin were injected intravenously (i.v.) and intraluminarily
      (i.l.) to determine their effects on catecholamine levels. I.v. injected toxins
      clearly altered catecholamine levels causing sharp rises in adrenaline and
      noradrenaline levels and at critical toxin concentrations sudden death ensued.
      Clostridium perfringens enterotoxin and alpha-toxin, Clostridium difficile
      enterotoxin (A) and cytotoxin (B), Escherichia coli STa toxin and staphylococcal
      enterotoxin B caused rises in catecholamine levels similar to that caused by E.
      coli endotoxin. Control rabbits showed very little or no obvious change in
      catecholamine levels. Clostridium difficile enterotoxin (A) and cytotoxin (B)
      injected i.v. exhibited synergy. Toxins injected into the duodenum, jejunum,
      ileum, cecum and large intestine caused behavioural changes ranging from reduced
      appetite and diarrhea to, in rare cases, death. Changes in the catecholamine
      levels of these animals however were not significantly different from those of
      the control animals. The results are discussed in relation to the possible effect
      of certain conditions (physiological, viral infections and environmental) which
      increase toxin permeability and allow absorption of these toxins, possibly
      resulting in sudden infant death.

PMID- 9271019
TI  - A technique for obtaining repeated liver biopsies from rats.
AB  - Many morphological, pharmacological and toxicological studies of hepatotoxicity
      require frequent sampling of liver over time. In the past this has been achieved
      by including large numbers of animals in the study and killing subgroups at
      different times. In this paper we describe a technique for repeated liver biopsy
      that procures sufficient liver tissue for histopathological assessment and for
      additional studies, for example measurement of hepatic iron concentration or
      vitamin A measurement. The advantages and disadvantages of this technique are
      discussed.

PMID- 9271020
TI  - Detection of minimal residual disease in an AML patient with trisomy 8 using
      interphase fish.
AB  - Patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)
      often exhibit clonal chromosomal abnormalities. Using a probe for the centromeric
      region of chromosome 8, fluorescence in situ hybridization (FISH) on interphase
      cells was used to detect trisomy 8 in an AML patient whose leukemia was
      characterised by the karyotype 47, XY, +8, del(9) (q21.1q32). We have
      demonstrated using FISH the presence of the trisomy at all stages of the
      patient's disease course (including remission, peripheral blood cell harvest and
      relapse), whereas conventional karyoptypic analysis was only able to detect the
      trisomy at diagnosis and clinical relapse. We have also shown using
      immunophenotyping, cell sorting and FISH, that the trisomic cells in this patient
      were restricted to the CD34+ subset of blood and bone marrow and could not be
      found in the CD 34-, T or B cell compartment. Overall we have shown FISH to be a
      rapid, quantitative method for the detection of cells with numerical chromosome
      abnormalities. FISH analysis of interphase cells provides valuable information on
      the status of the whole population, rather than just cycling cells, and can be
      applied successfully to monitor the level of leukemic cells.

PMID- 9271022
TI  - Prevalence of respiratory viruses and Mycoplasma pneumoniae in sputum samples
      from unselected adult patients.
AB  - Sputum samples from adult patients are routinely used for bacteriological tests,
      but not for the diagnosis of viral/mycoplasmal infections. We examined 511 sputum
      samples submitted for bacterial tests from patients at the Royal Adelaide
      Hospital. Each specimen was tested directly (and after six days of cell culture
      amplification) for antigens to influenza A and B, parainfluenza 1, 2 and 3,
      adenovirus, respiratory syncytial virus (RSV) and Mycoplasma pneumoniae.
      Respiratory viruses or M. pneumoniae were found in 11% of all specimens but were
      most common (14%) in sputa reported as containing only "oral flora". Respiratory
      virus or M. pneumoniae infection was significantly more common in medical
      patients (12%) than in surgical patients (5%), and was most common in oncology
      (hematology/radiotherapy) patients (25%). Influenza A and RSV were equally common
      in medical patients, while RSV was the most frequent isolate in oncology
      patients. Respiratory viral infection is an underdiagnosed condition in adults,
      particularly the immunocompromised, which can be successfully diagnosed by
      virological examination of sputum.

PMID- 9271021
TI  - Hodgkin's cells express CD83, a dendritic cell lineage associated antigen.
AB  - Hodgkin's cells (HC) are considered to be the malignant cells of Hodgkin's
      disease (HD), but despite extensive studies, no conclusive evidence has emerged
      regarding their non-malignant counterpart and the ontogeny of these cells remains
      controversial. The analysis of a possible dendritic cell (DC) origin of HC has
      been hampered to date by the lack of a DC lineage specific marker. The expression
      of the two DC-associated antigens CD83 and CMRF-44, the B lymphocyte restricted
      molecule CD79, and the costimulator molecule CD86, was examined in lymph nodes
      from 23 HD patients using immunohistological techniques. The majority of HC
      expressed the CD83 (22/23) and CD86 antigens (20/23), whereas expression of the
      CMRF-44 antigen was variable (10/23) and usually only a subpopulation of HC
      stained. In contrast, the CD79 antigen was absent from most HC (17/23). The
      presence of the CD83 antigen on HC in the absence of the CD79 antigen supports a
      possible DC lineage origin for some HC. Regardless of its role in lineage
      assignment, CD83 may become a useful immunohistological marker for HD as the CD83
      antigen was present on most HC.

PMID- 9271023
TI  - Increasing vancomycin resistance in Enterococcus spp. in Australia: facing the
      challenge in the laboratory.
AB  - High level vancomycin resistance in enterococci (VRE) is increasing in Australia.
      If the spread of VRE is to be checked, then it is vital for laboratories to be
      able to detect it promptly and accurately. We have established a rapid and
      accurate screening method using Enterococcosel agar supplemented with 6 mg/l
      vancomycin. It can recover VRE from spiked feces, it may be used to screen feces
      for carriage of VRE and it is not subject to the confounding effects which feces
      introduce to broth enrichment culture.

PMID- 9271024
TI  - Sudden cardiac death in familial hypertrophic cardiomyopathy: are "benign"
      mutations really benign?
AB  - Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disorder
      characterised predominantly by left ventricular hypertrophy and sudden cardiac
      death. Mutations in the cardiac beta-myosin heavy chain gene have been identified
      in several families and designated as "benign" or "malignant". We describe a
      family (family L) with a "benign" mutation in which early sudden cardiac death
      has occurred. The family was studied by clinical, electrocardiographic and
      echocardiographic assessment. DNA analysis involved screening for the six most
      common cardiac beta-myosin heavy chain gene mutations using allele specific
      oligonucleotide probes and restriction enzyme analysis. The Val606Met missense
      mutation was found. This mutation has been described in four families as being
      "benign" since it was associated with low penetrance and a near normal life span.
      Sudden cardiac death was an infrequent finding. In contrast, family L has a more
      malignant clinical picture with one sudden death in three affected individuals.
      The proband died suddenly at age 14 years during exercise. Designating gene
      mutations in FHC as benign or malignant has major clinical implications. As these
      mutations have only been described in a limited number of families, caution needs
      to be taken when interpreting genotype-phenotype correlations in this disorder.

PMID- 9271025
TI  - B-cell target DNA quantity is a critical factor in the interpretation of B-cell
      clonality by PCR.
AB  - Criteria for the assessment of clonality by Southern blotting are well
      established but this is not the case for polymerase chain reaction (PCR)-based
      assays. Our studies, and infrequent reports in the literature, indicate that B
      cell clonality may be erroneously inferred if only small numbers of polyclonal B
      cells are present in test samples. In order to establish criteria to minimise the
      false positive assignment of B-cell clonality, DNA was analysed in a semi-nested
      PCR to detect rearrangement of the immunoglobulin heavy chain gene using a range
      (1 microgram-0.1 ng) of target DNA amounts from four tonsils and five lymph nodes
      showing reactive follicular hyperplasia, and from six B-cell lymphomas. A
      discrete, narrow band of PCR product of constant size was detected throughout the
      range of target DNA amounts in most lymphomas indicating the presence of a
      monoclonal B-cell population. In contrast, from the non-malignant tonsils and
      lymph nodes, larger target amounts generated a broad band of PCR products
      indicating populations of polyclonal B-cells, but smaller target amounts
      generated discrete, narrow PCR product bands of inconstant size indicating oligo-
      or monoclonal B-cell populations. Results of this study demonstrate that a range
      of DNA target amounts should be tested when the proportion of B-cells in a sample
      is unknown, thus preventing the analysis of insufficient target DNA which may
      lead to the false assignment of clonality.

PMID- 9271026
TI  - Association of hypercalcemia, PTHrP expression and disease progression in a woman
      with primary squamous cell carcinoma of the breast.
AB  - This paper describes humoral hypercalcemia of malignancy (HHM) associated with
      squamous cell carcinoma (SCC) of the breast and its association with assayed
      levels of parathyroid hormone related protein (PTHrP). A 57-year-old woman
      presented with locally advanced SCC of the breast. The diagnosis was supported by
      serum analysis and histological and immunohistochemical findings. She was
      initially treated with chemotherapy to reduce the tumor bulk but developed
      symptomatic hypercalcemia after on course. The hypercalcemia was effectively
      treated with intravenous amino hydroxy propildene diphosphonate. Subsequently the
      tumor progressed despite multimodality therapy and was associated with recurrent
      hypercalcemia. The patient died nine months after presentation.

PMID- 9271027
TI  - Two case reports of breast carcinoma associated with prolactinoma.
AB  - Two cases of breast carcinoma associated with prolactinoma are presented.
      Literature review reveals only five previous case reports of this association.
      Both of our cases occurred in women, aged 55 and 34. Both were typical of the
      reported cases in that they had long histories of amenorrhea before diagnosis of
      prolactinomas and breast carcinomas. One patient had a three and a half year
      history of atypical ductal hyperplasia and a prominent intraduct component in the
      invasive tumor. Both had axillary lymph node metastases. The significance of the
      association of breast carcinoma with prolactinoma is discussed. Whereas studies
      in animals have shown prolactin to be an initiator and promoter of breast
      carcinoma, studies in humans have been inconclusive. Some studies have shown
      raised levels of prolactin in patients with breast carcinoma and their daughters,
      while others have not. The paucity of case reports linking breast carcinoma and
      prolactinoma may indicate that the association is mere coincidence, but studies
      evaluating the relationship between breast carcinoma and all forms of
      hyperprolactinemia need to be conducted before a causal link is dismissed.
      Prolactin may act as a cofactor with, for example, estrogen or stress, to induce
      breast carcinoma.

PMID- 9271028
TI  - Two cases of fatal strongyloidiasis in Hong Kong.
AB  - Two cases of fatal strongyloidiasis associated with diabetes mellitus and
      malnutrition are reported. The patients presented with repeated vomiting and
      upper gastrointestinal bleeding respectively. Unusual findings in these two
      patients included: unexplained peripheral leukocytosis, pulmonary infiltrates,
      gastric aspirate leukocytosis, progression of gastrointestinal symptoms and
      concurrent presence of adult worms, eggs, filariform and rhabditiform larvae of
      Strongyloides stercoralis in alimentary canal specimens. Both patients succumbed
      while receiving treatment with mebendazole. The present report illustrates that
      unexplained gastrointestinal symptoms with extensive scratch marks below the
      umbilicus can be important clues to early diagnosis of the disease. In addition,
      the various presentations of S. stercoralis infestation are discussed with
      reference to predisposing factors. Current trends in laboratory diagnosis and
      therapeutic considerations are also delineated.

PMID- 9271029
TI  - Helicobacter pylori in areas of intestinal metaplasia in gastric antral mucosa.
AB  - Colonization of areas of intestinal metaplasia by Helicobacter pylori is rare and
      there is only one report in the literature of this organism colonizing areas of
      intestinal metaplasia in the antral mucosa. We report two more cases where H.
      pylori were seen in the gastric pits with intestinal metaplastic changes in the
      antral biopsy specimens.

PMID- 9271030
TI  - Comparative in vitro susceptibility of Burkholderia Pseudomallei to cefpirome,
      ceftazidime and cefepime.

PMID- 9271031
TI  - Alpha-1-antitrypsin kinetics.

PMID- 9271032
TI  - Ease of isolation and semiquantitative culture of Bartonella henselae from cats
      in Melbourne.

PMID- 9271033
TI  - Prophylactic neonatal surgery and infectious diseases.
AB  - Infections worldwide are the primary cause of morbidity and mortality today. The
      need for prevention is essential. Prophylactic surgery with the reduction of
      infectious disease has been available for many millennia, but its recognition has
      been questionably accepted. This article presents evidence of former times when
      circumcision was performed in the ancient Egyptian, Coptic and Ethiopian
      cultures, probably as a therapeutic measure to combat the ravages of schistosomal
      infectious symptomatology. How this health measure was converted to a religious
      rite and the confusion caused by this misunderstanding is fully explored. The
      association of an operative procedure as a religious ritual among Jews, and
      Christian Biblical ambiguity toward it, has further clouded the issue. Neonatal
      circumcision has been perpetuated in many societies and cultures, not because of
      the Jews and their Covenant of Circumcision, but because of its merit as a
      secular surgical prophylactic health measure. This article explores an
      interesting issue from its beginning to contemporary research and findings that
      justify the procedure as a viable option in maintaining and promoting quality
      genital health care for males of all ages.

PMID- 9271034
TI  - Clinical applications of C-reactive protein in pediatrics.
AB  - The body of literature concerning studies of the applications of CRP measurement
      in the pediatric population continues to grow. Based on current data serial CRP
      measurements appear to be most useful for monitoring patient response to therapy
      after the primary diagnosis of invasive infectious or inflammatory diseases, for
      monitoring patients after major surgical procedures and those with serious burns.
      Monitoring CRP over time may be used to assess for recrudescent disease, a
      secondary process or ineffective therapy. In addition CRP appears to be suited to
      most applications for which the ESR is used but offers many advantages. At
      present there are no objective outcome-based clinical trial data to justify using
      CRP values alone, whether elevated or normal, as a basis for management decisions
      regarding instituting or withholding antimicrobial therapy, or its early
      discontinuance for patients suspected of having neonatal sepsis, meningitis,
      bacteremia or pneumonia, regardless of immune status. In addition, because of
      significant inconsistencies among studies for which CRP has been applied to
      differential diagnosis of bacterial vs. viral diseases, including meningitis,
      acute otitis media and lower respiratory tract infection, we cannot recommend it
      for this purpose. Data do not support a role for CRP in differential diagnosis of
      acute appendicitis or for localizing urinary tract infections.

PMID- 9271035
TI  - Polymerase chain reaction for Streptococcus pyogenes used to evaluate an optical
      immunoassay for the detection of group A streptococci in children with
      pharyngitis.
AB  - BACKGROUND: In evaluations of sensitive rapid tests for group A streptococci such
      as the optical immunoassay (OIA), some samples are positive by the antigen test
      but negative by culture. A method is needed for resolving these discrepant
      results. OBJECTIVE: To develop a PCR-based assay to detect group A streptococci
      and to use it to establish a reference standard for evaluating an OIA for group A
      streptococcal antigen. METHODS: A PCR assay that detects a segment of the MF gene
      of Streptococcus pyogenes was developed for the detection of group A streptococci
      in throat swabs. Paired swabs were obtained from 200 children with symptomatic
      pharyngitis and used to perform OIA, agar culture, broth-enhanced culture and
      PCR. As a reference standard any patient with group A streptococci detected by
      either culture or PCR was considered to be truly positive. RESULTS: In comparison
      to agar and broth-enhanced culture procedures, OIA had sensitivities of 82 and
      80% and specificities of 87 and 89%, respectively. Eight (44%) of 18 samples that
      were positive by OIA but negative by culture were positive for group A
      streptococci by PCR. Compared with the reference standard, sensitivities were OIA
      76%, agar culture 79%, broth-enhanced culture 86% and PCR 96%. The specificity of
      OIA was 92%. CONCLUSIONS: PCR can be used to establish a reference standard for
      evaluating rapid tests for group A streptococci. With this reference standard OIA
      was nearly as sensitive as but less specific than agar culture for detection of
      group A streptococci. Maximum detection requires use of both tests.

PMID- 9271036
TI  - Activation of the CD95 system increases with disease progression in human
      immunodeficiency virus type 1-infected children and adolescents.
AB  - BACKGROUND: Increased apoptosis in infected as well as noninfected cells has been
      invoked in CD4+ T helper cell depletion during HIV-1 infection. A strong increase
      in the expression of CD95 (APO-1/Fas) and CD95 ligand, key regulators of
      apoptosis in normal T cells, has previously been described in freshly isolated T
      cells from HIV-1-positive children when compared with healthy age-matched
      controls. We also found an increase in spontaneous as well as specific CD95
      mediated apoptosis in CD4+ and CD8+ T cells from these patients. However, the
      relationship of these findings to disease progression in children with HIV
      infection is not known. MEASUREMENTS AND SUBJECTS: We studied expression of CD95
      and CD95 ligand as well as sensitivity towards spontaneous and anti-CD95
      triggered apoptosis of T cells in 33 HIV-1-positive children and adolescents in
      different disease stages. RESULTS: Loss of CD4+ T cells in vivo was paralleled by
      an increase in the percentage of CD95 high T cells and an increase in anti-CD95
      induced apoptosis of CD4+ T cells. CD95L mRNA was constantly up-regulated in T
      cells from patients in intermediate disease stages whereas patients with normal
      CD4 counts and patients with advanced T cell loss showed CD95 ligand-mRNA levels
      in or slightly above the range of normal controls. CONCLUSIONS: Disturbed
      regulation of the CD95 system may play an important role in the development of
      immunodeficiency during the course of HIV infection in children.

PMID- 9271037
TI  - Tolerance of pyrazinamide in short course chemotherapy for pulmonary tuberculosis
      in children.
AB  - BACKGROUND: This prospective study was performed to evaluate the tolerance of
      pyrazinamide in short course chemotherapy in children. METHODS: A total of 114
      children ages 6 months to 15 years (4.5 +/- 3.4 years) with diagnosed pulmonary
      tuberculosis from 1985 to 1995 entered the trial. A 2-month regimen of isoniazid,
      rifampin and pyrazinamide, followed by rifampin and isoniazid for the remaining 4
      months, was administered orally to all children. Clinical adverse effects
      specifically investigated were gastrointestinal disturbances, rash, signs of
      hepatotoxicity and arthralgias. Laboratory toxicity data (number of leukocytes,
      erythrocyte sedimentation rate, aspartate aminotransferase, alanine
      aminotransferase and serum uric acid) were collected before treatment and 1, 3
      and 5 months after the beginning of chemotherapy. RESULTS: Clinical adverse
      effects were mild in all cases. Three children (2.6%) had fever and 5 (4.4%) had
      gastrointestinal disturbances. Aspartate aminotransferase and alanine
      aminotransferase mean values showed no differences along time and no patients had
      clinical signs of hepatotoxicity. Only 11 children (19.6%) showed a slight
      increase in alanine aminotransferase (< 194 units/l). Serum uric acid increased
      in 92.2% of the children compared with pretreatment values. This increase
      remained within the normal range in all but 9.8% of patients. There was a
      significant increase in uric acid mean concentrations after 1 month of therapy
      (from 3.7 +/- 0.7 mg/dl to 5.7 +/- 1.6 mg/dl, P < 0.05), which fell again (4.0 +/
      1.1) 1 month after pyrazinamide was stopped. There were no signs of gout or
      arthralgias. In no case was the treatment interrupted. CONCLUSION: The addition
      of pyrazinamide in chemotherapy for pulmonary tuberculosis in children was found
      to be safe. The slight increase in uric acid concentration during its
      administration had no recognized adverse consequences.

PMID- 9271038
TI  - Prospective study of fluconazole therapy in systemic neonatal fungal infection.
AB  - BACKGROUND: Standard neonatal systemic antifungal therapy with amphotericin B and
      flucytosine can be associated with toxicity, drug resistance and the need for
      prolonged venous access. There is consequently a need for alternative treatment
      options. OBJECTIVES: To assess the efficacy and safety of fluconazole in the
      treatment of systemic neonatal fungal infections. METHOD: Open, nonrandomized
      evaluation of fluconazole treatment in 20 consecutively enrolled neonates with
      systemic fungal infection. RESULTS: Clinical and microbiologic cure was achieved
      in 12 of 19 (63%) of infants treated. One additional infant received prior
      amphotericin B therapy and is included for assessment of side effects. One infant
      with Torulopsis glabrata infection failed treatment. Six infants died of Gram
      negative bacterial infection and other intercurrent medical problems. CONCLUSION:
      Fluconazole appeared to be safe and effective for treatment of systemic candidal
      infection in the neonate although more data are required in very low birth weight
      infants.

PMID- 9271039
TI  - A prospective study of neonatal sepsis and meningitis in southern Israel.
AB  - OBJECTIVE: To study the epidemiology of neonatal sepsis and meningitis in the
      Negev area of southern Israel. DESIGN: A prospective 8-year study conducted at
      the neonatal intensive care unit and pediatric wards of the Soroka University
      Medical Center. RESULTS: Two hundred twenty-nine cases of hospital and community
      acquired neonatal sepsis occurred during the study period. Thirty-two patients
      (14%) were meningitis. During this period 70,709 births (59% Jews and 41%
      Bedouins) were recorded; thus the rates of neonatal sepsis and meningitis were
      3.2 and 0.5/1000 live births, respectively. One hundred seventeen (4/1000 live
      births) cases were recorded in Bedouins and 112 (2.6/1000 live births) in Jewish
      neonates (P < 0.001). Twenty-six percent of all sepsis cases occurred within < 24
      h from birth, 25% from Days 2 to 7 of life and 49% between Days 8 and 28. A total
      of 251 organisms that were considered true pathogens were isolated. Fifty-seven
      of all isolates were Gram-negative organisms (mainly Klebsiella pneumoniae (20%)
      and Escherichia coli (16%)). Gram-positive organisms were isolated in 41% of
      cases. Although E. coli was the most frequently recovered Gram-negative pathogen
      in community-acquired late onset sepsis, Klebsiella and Enterobacter spp.
      represented the most commonly isolated Gram-negative organisms in nosocomial late
      onset sepsis. All Staphylococcus aureus isolates recovered in late onset sepsis
      were nosocomial. The incidence of Streptococcus agalactiae was 3 times higher in
      early onset sepsis than in late onset sepsis. All cases of Streptococcus
      pneumoniae sepsis occurred in Bedouins. CONCLUSIONS: Neonatal sepsis and
      meningitis rates in southern Israel are similar to those reported in Western
      Europe and the United States. The incidence of neonatal sepsis is significantly
      higher for Bedouins than for Jewish neonates. The distribution of the main
      pathogens is different in southern Israel and although Gram-negative enteric
      organisms are predominant, S. agalactiae plays a relatively minor role in the
      etiology of sepsis during the first month of life. In southern Israel the
      etiology of community-acquired late onset sepsis is different from that of
      nosocomial late onset sepsis.

PMID- 9271040
TI  - The contribution of infectious diseases to infant mortality in Alaska.
AB  - BACKGROUND: Based on death certificates to determine cause of death, current
      research suggests that infectious diseases are less important causes of infant
      mortality than in the past. METHODS: To determine the contribution of infectious
      diseases to infant mortality and the sensitivity of death certificates for
      identifying infectious disease causes of death, we examined information from
      multiple sources for a population-based sample of infant deaths that occurred in
      Alaska during 1992 through 1994. RESULTS: We collected information for 181 of 272
      reported infant deaths and identified 48 infants for whom an infection was a
      primary (n = 15), contributing (n = 12) or suspected (n = 21) cause of death
      (infectious disease-related infant mortality rate, 2.2/1000 live births). Of
      these 48 deaths 27 were associated with a maternal peripartum infection and 15
      were associated with a postneonatal respiratory tract infection. A specific
      organism was identified for 15 of 29 infants who died during the neonatal period
      and for 5 of 19 infants who died during the postneonatal period (including 2 with
      coagulase-negative Staphylococcus and the rest with a variety of other
      organisms). Death certificates identified an infectious disease as a primary or
      contributing cause of death for 19 infants (sensitivity, 40%) and reported a
      specific organism for 4 infants. CONCLUSIONS: Infectious diseases caused or
      contributed to a high proportion of infant mortality in Alaska during 1992
      through 1994. Death certificates had poor sensitivity for identifying infectious
      disease-related infant deaths.

PMID- 9271041
TI  - Haemophilus influenzae type b disease and vaccination in Latin America and the
      Caribbean.
AB  - OBJECTIVE: Conjugate vaccines are highly effective in preventing Haemophilus
      influenzae type b (Hib) diseases. Data on the epidemiology of Hib disease in
      Latin America and the Caribbean are not easily accessible, are incomplete and are
      deserving of critical analysis. METHODS: Relevant information in Spanish, English
      and Portuguese from over 20 regions in 16 countries was reviewed, with special
      attention to all Hib diseases and to children < 5 years because of their
      proneness to disease. Total number of cases and deaths were estimated from the
      incidence rates obtained from 10 studies. RESULTS: Taking into account variation
      between among countries, the overall incidence of Hib meningitis at age 0 to 4
      years was estimated as 35 per 100,000, which would imply 20,000 cases annually in
      the region. An estimated rate of 60 per 100,000 for all Hib disease suggests
      33,000 cases per annum. In all age groups at least 40,000 annual cases and 5000
      deaths occurred annually. Given that the true role of Hib pneumonia is unknown
      because of data are much lacking for nonbacteremic cases, these figures are
      probably underestimations. Because large scale vaccination programs are being
      implemented in only 3 countries, the impact on Hib epidemiology has been minimal.
      CONCLUSIONS: Hib diseases are common in Latin America and the Caribbean, and use
      of conjugate vaccines is minor. Concurrently with better epidemiologic studies,
      their use should be extended, preferably in combination with other vaccines.
      Making Hib diseases notifiable would be one step for better recognition of their
      importance.

PMID- 9271042
TI  - Immunogenicity and reactogenicity of a booster dose of diphtheria, tetanus,
      acellular pertussis and inactivated poliomyelitis vaccines given concurrently
      with Haemophilus type b conjugate vaccine or as pentavalent vaccine.
AB  - BACKGROUND: The high reactogenicity of whole cell pertussis vaccines discourages
      their use in children. While acellular pertussis vaccines are less reactogenic,
      their use in diphtheria-tetanus-acellular pertussis (DTPa)-based combinations
      with Haemophilus influenzae type b conjugate vaccine (Hib) and poliomyelitis
      vaccines must be evaluated. OBJECTIVES: To assess the immunogenicity and
      reactogenicity of a booster dose of diphtheria, tetanus, acellular pertussis and
      inactivated poliomyelitis vaccine (DTPa-IPV) given concurrently with Hib as a
      mixed vaccine or as separate injections, in comparison with a whole cell
      pertussis vaccine (DTPw-IPV-Hib). MATERIALS AND METHODS: This open, randomized,
      controlled study involved 145 healthy children ages 15 to 24 months.
      Immunogenicity was evaluated for all vaccine antigens, and reactogenicity was
      assessed with diary cards. RESULTS: Serum antibody responses to all vaccine
      antigens was at least as good as that observed with the pentavalent whole cell
      vaccine. DTPa-IPV was well-tolerated and less reactogenic than the DTPw-IPV
      vaccine. Administration of DTPa-IPV and Hib vaccine either separately or mixed
      did not alter the immunogenicity or reactogenicity profiles. CONCLUSION: DTPa-IPV
      vaccine, either separately or mixed with Hib vaccine, was at least as immunogenic
      and less reactogenic than the DTPw-Hib vaccine. Mixing DTPa-IPV and Hib vaccines
      did not alter the safety profile when compared with separate injections of both
      vaccines. A mixed DTPa-IPV-Hib vaccine can be recommended for routine use as a
      booster dose in primed children.

PMID- 9271043
TI  - Local and systemic host defense mechanisms against Candida: immunopathology of
      candidal infections.

PMID- 9271044
TI  - Unusual presentations of nontuberculous mycobacterial infections in children.

PMID- 9271045
TI  - Concurrent ganciclovir and foscarnet treatment for cytomegalovirus encephalitis
      and retinitis in an infant with acquired immunodeficiency syndrome: case report
      and review.

PMID- 9271046
TI  - Zygomycosis in neonates.

PMID- 9271047
TI  - Middle ear effusion concentrations of cefixime during acute otitis media with
      effusion and otitis media with effusion.

PMID- 9271048
TI  - Vibrio vulnificus sepsis in a child with Diamond-Blackfan syndrome.

PMID- 9271049
TI  - Pseudomonas aeruginosa endophthalmitis after lung transplantation for cystic
      fibrosis.

PMID- 9271050
TI  - Perforation of the aorta associated with Staphylococcus aureus endocarditis.

PMID- 9271051
TI  - Cervical adenitis and deep neck infection caused by Streptococcus pneumoniae.

PMID- 9271052
TI  - Your diagnosis, please. Encephalitis in a boy from South Carolina.

PMID- 9271054
TI  - Gastroenteritis caused by Listeria monocytogenes in a private day-care facility.

PMID- 9271053
TI  - Variations in the treatment of common infections.

PMID- 9271055
TI  - Hemolytic-uremic syndrome after Escherichia coli urinary tract infection.

PMID- 9271056
TI  - Mycobacterium chelonae vs. abscessus.

PMID- 9271057
TI  - Monodisperse hydrolyzed poly(glycidyl methacrylate-co-ethylene dimethacrylate)
      beads as a stationary phase for normal-phase HPLC.
AB  - The basic characteristics of a rugged, stable, and highly efficient polymeric
      stationary phase for normal-phase HPLC prepared by hydrolysis of porous
      monodisperse poly(glycidyl methacrylate-co-ethylene dimethacrylate) beads have
      been studied and compared with those of bare Nucleosil silica and Nucleosil
      silica-diol. As a result of their overall chemical composition and the more than
      10-fold larger surface coverage with hydroxyl groups, the polymer beads provide
      much higher retention of model solute molecules. In contrast to silica hydroxyls,
      all of the polymer surface diol groups are chemically equal and homogeneously
      distributed over all of the surface. In addition, they are less acidic than
      typical silanol functionalities. The exceptional selectivity of the polymeric
      column can be controlled by the composition of the mobile phase, as demonstrated
      with a broad spectrum of separations involving positional isomers of benzene
      derivatives, nonpolar isobutylene copolymers with minute composition differences,
      and hydrophilic poly(ethylene oxides) differing only in their chain length.
      Unlike silica phases, the properties of the polymeric stationary phrase are not
      affected by the presence of water in the mobile phase. As a result, repetitive
      gradient separations in eluents ranging in polarity from hexane through
      tetrahydrofuran to water can be easily accomplished.

PMID- 9271058
TI  - On-line pyrolysis as a limitless reduction source for high-precision isotopic
      analysis of organic-derived hydrogen.
AB  - On-line pyrolysis is described as an alternative to chemical means for reducing
      organic compounds to hydrogen gas for hydrogen isotopic analysis by continuous
      flow isotope ratio mass spectrometry. An empty ceramic tube, held at temperatures
      above 1000 degree C, is used in-line to pyrolyze organic compounds separated by
      gas chromatography and is followed by a hydrogen-selective filter and isotope
      ratio mass spectrometer for hydrogen purification and isotopic measurement.
      Precision of light gas D/H isotopic measurement over several-fold signal
      intensity is shown to average SD < 2% (delta D), with corrections for ion source
      nonlinearities. It is demonstrated that isotopic measurement using pyrolysis is
      indefinitely stable, as opposed to the gradual loss of isotopic accuracy using on
      line chemical reactors due to degradation of the reducing capacity of reactor
      metals. Pyrolytic conversion to hydrogen becomes more efficient with increasing
      temperature, although quantitative conversion was not achieved at the highest
      temperature tested (1150 degree C) in our system. In addition, pyrolysis
      efficiency varies with compound type; therefore, the technique requires a
      separate calibration for each compound of interest. This approach shows promise
      as a component of a robust and low-maintenance system.

PMID- 9271059
TI  - A microfabricated device for rapid protein identification by microelectrospray
      ion trap mass spectrometry.
AB  - Nanoelectrospray mass spectrometry, the infusion at low flow rates of unseparated
      peptide mixtures representing protein proteolytic digests into an electrospray
      ionization mass spectrometer (MS), has been shown to be a suitable method for the
      analysis of small amounts of proteins. However, the current technique is time
      consuming, tedious, and difficult to automate. We used microfabrication
      technologies to construct a device for the sequential infusion of different
      peptide samples into an electrospray ionization MS without the need for sample
      manipulation. In this device, etched sample and buffer reservoirs are connected
      via etched channels to microelectrospray ion source. Peptide samples, typically
      unseparated tryptic digests of proteins, are applied to different reservoirs. A
      flow of liquid originating from a specific reservoir is generated and selectively
      directed toward the microsprayer and the MS by electroosmotic pumping. The
      analyte proteins are identified by searching sequence databases with the
      information contained in the collision-induced spectra of selected peptides. With
      this system, we have achieved a limit of detection in the low femtomoles per
      microliter range for peptide standards. We also show that samples deposited in
      different reservoirs can be sequentially mobilized without cross-contamination
      and that proteins can be conclusively identified at the low femtomoles per
      microliter level. The successful coupling online of microfabricated devices to an
      electrospray ionization MS represents an essential step toward the construction
      of automated, high-throughput, and high-sensitivity analytical systems.

PMID- 9271060
TI  - Development of a nanoscale liquid chromatography/electrospray mass spectrometry
      methodology for the detection and identification of DNA adducts.
AB  - In this work, the coupling of liquid nanochromatography to NanoFlow electrospray
      mass spectrometry was evaluated for the detection of DNA adducts. The NanoFlow ES
      LC/MS system was compared with the capillary and conventional ES LC/MS system by
      analyzing an in vitro reaction mixture resulting from the interaction of 2'
      deoxyguanosine 5'-monophosphate with bisphenol A diglycidyl ether and by
      injecting 2'-deoxyadenosine. By using NanoFlow ES LC/MS, the mass sensitivity
      could be improved by a factor of 3300. Three different injection methods used in
      liquid nanochromatography, i.e., split, large-volume, and column-switching
      injections were compared in terms of sensitivity. Furthermore, NanoFlow ES LC/MS
      was used to detect 2'-deoxynucleotide adducts isolated from an in vitro mixture
      of calf thymus DNA and bisphenol A diglycidyl ether. Different 2'-deoxynucleotide
      adducts could be identified by monitoring typical product ions, diagnostic for
      the adducts.

PMID- 9271061
TI  - Imaging of boron in tissue at the cellular level for boron neutron capture
      therapy.
AB  - Glioblastoma multiforme, and other tumors involving the brain, are undergoing
      experimental treatment with a promising new technique: boron neutron capture
      therapy (BNCT). BNCT relies on the capture of thermal neutrons by boron deposited
      biochemically in the tumor and the subsequent fission of the boron into energetic
      lithium ions and alpha particles. An important requirement for improved BNCT is
      the development of more selective boron delivery mechanisms. The ability to image
      the boron concentration in tissue sections and even inside individual cells would
      be an important aid in the development of these delivery mechanisms. We have
      compared both sputter-initiated resonance ionization microprobe (SIRIMP), which
      combines resonance ionization with a high-energy pulsed focused sputter ion beam
      and mass spectrometric detection of ions, with laser atomization resonance
      ionization microprobe (LARIMP), which uses a laser pulse instead of an ion pulse
      for the atomization process, to determine their characteristics in locating and
      quantifying boron concentrations as a function of position in tissues obtained
      from a rat which had been infused with a BNCT drug. The data show that the
      SIRIMP/LARIMP techniques are well suited for quantitative and ultrasensitive
      imaging of boron trace element concentrations in biological tissue sections. The
      LARIMP mode could be used to quickly determine the spatial boron concentration
      with intercellular resolution over large areas down to the low nanograms-per-gram
      level, while the SIRIMP mode could be used to determine the spatial boron
      concentration and its variability in intracellular areas.

PMID- 9271062
TI  - Two-dimensional analysis of recombinant E. coli proteins using capillary
      isoelectric focusing electrospray ionization mass spectrometry.
AB  - On-line combination of capillary isoelectric focusing with electrospray
      ionization mass spectrometry is applied for a two-dimensional analysis of
      Escherichia coli proteins. The proteins are focused and cathodically mobilized in
      a polyacrylamide coated capillary. At the end of the capillary, various protein
      zones are analyzed by mass spectrometry coupled through an electrospray
      interface. Comparisons with silver-stained two-dimensional gel electrophoresis
      are made with regard to mass determination, resolution, speed, and sensitivity.
      Direct identification of a recombinant fusion protein of glutathione S
      transferase and striped bass growth hormone is achieved without any prior protein
      isolation procedures.

PMID- 9271063
TI  - Analysis of macromolecules using nanoelectrospray ionization mass spectrometry
      and low-energy collision activation.
AB  - The mass spectrometric analysis of several proteins using nanoelectrospray
      (nanoES) with elastic collisions showed an improvement in the sensitivity over
      nanoES without collisional activation. We believe this effect is due to a better
      declusterization/ionization process. Optimization of the collision parameters can
      be easily performed during the long experiment time allowed using the nanoES
      source. Moreover, an apparent shift in the charge-state distribution is observed,
      with lower charged ions becoming relatively more abundant with increasing either
      target gas pressure or kinetic energy of the precursor ions. Higher charge-state
      ions might be expected to have higher collision frequencies and correspondingly
      lose more kinetic energy than lower charge-state ions.

PMID- 9271064
TI  - Structural analysis of permethylated oligosaccharides by electrospray tandem mass
      spectrometry.
AB  - Electrospray tandem mass spectrometry used in conjunction with reversed-phase
      liquid chromatography was applied to characterize permethylated oligosaccharides.
      N-Acetylhexosamine-containing carbohydrates yielded under these conditions
      promoted molecular ions which underwent extensive fragmentation, even under low
      energy collision-induced dissociation. MS/MS spectra of [M + H]+ ions are
      characterized by simple fragmentation patterns which result from cleavage of the
      glycosidic bonds and thus allow a straightforward interpretation. A systematic
      study of various oligosaccharides showed that information on sugar sequence and
      branching could be obtained. The nature of the substituent linked in position 3
      of HexNAc-containing fragments could easily be assigned as the result of a
      specific secondary fragmentation process. The nature of some internal fragments
      was established on the basis of MS/MS spectra of derivatives 18O-labeled at the
      reducing end. Furthermore, MS/MS experiments carried out on fragment ions were
      proven to be useful for the structural characterization of oligosaccharide
      subunits. Thus, this approach constitutes a powerful tool for the structural
      assignment of moieties derived from larger glycans.

PMID- 9271065
TI  - End-label free-solution electrophoresis of the low molecular weight heparins.
AB  - The intact heparins are highly charged oligosaccharides. Their charge
      polydispersity and the possible occurrence of numerous isomers complicate the
      analysis of these biomedically important glycoconjugates. After unsuccessful
      attempts to resolve the low molecular weight heparins in entangled matrixes, or
      through the use of counterions (Stefansson, M.; Novotny, M. V. Anal. Chem. 1994,
      66, 3466-3471), we have designed a unique end-label reagent to incorporate both a
      fluorescent moiety and a desirable frictional increment to the analyte molecules.
      The resolution of small oligomers was improved dramatically following this
      approach. We also propose a scheme, based on the end-label free-solution
      electrophoresis model (Mayer, P.; Slater, G. W.; Drouin, G. Anal. Chem. 1994, 66,
      1777-1780), that could potentially predict the migration times of some oligomers
      of complex heparin mixtures.

PMID- 9271066
TI  - Quantitative determination of short single-stranded oligonucleotides from blood
      plasma using capillary electrophoresis with laser-induced fluorescence.
AB  - The quantitative determination of short (< 20 bases) single-standed (ss-)
      oligonucleotides (oligos) from blood plasma using capillary gel electrophoresis
      with laser-induced fluorescence is reported. Oligos were derivatized on column
      after equilibration of the column with a 1:150 dilution of OliGreen dye. The
      resulting fluorescent complex was detected and measured with an argon ion laser
      detector using excitation/emission wavelengths of 488/520 nm, respectively. The
      method involves precipitation of plasma proteins with phenol-chloroform followed
      by dilution and drop analysis in nanopure water for 30 min on a 0.025 microns
      cellulose acetate membrane. This treatment lowers the ionic strength of the
      plasma sample resulting in a significant improvement of the electrokinetic
      loading (5 kV, 10 s) of the analyte. Optimal electrophoretic separation was
      achieved at 13 kV using 4 M urea in a 10% polyacrylamide gel filled capillary,
      100 mM Tris borate as the running buffer, and a temperature of 30 degrees C.
      Oligos were determined in the presence of p(dT)20/40 as internal standard. The
      observed migration times were 6.35 and 6.60 min for the oligo and internal
      standard, respectively. The migration times and fluorescent yield of the complex
      were temperature dependent. Increasing the separation temperature (20 to 60
      degrees C) resulted in a decrease in the migration time and fluorescent yield of
      the oligonucleotide-dye complex. A linear response over a broad concentration
      range (0.02-1.5 micrograms/mL, R2 = 0.997) was obtained. The limit of
      quantitation was set at 20 ng/mL (CV% = 11.3%). The intraday variability was
      9.44, 5.28, and 9.2% for 190, 760, and 1520 ng/mL plasma samples, respectively.
      Data are presented to illustrate the practicality of the method for the
      pharmacokinetic evaluation of GS522 and potential metabolites in plasma after
      intravenous administration to rats.

PMID- 9271067
TI  - Behavior and use of nonaqueous media without supporting electrolyte in capillary
      electrophoresis and capillary electrochromatography.
AB  - Five nonaqueous solvents (acetonitrile, methanol, N,N-dimethylformamide, dimethyl
      sulfoxide, formamide) and deionized water were investigated for their ability to
      support electroosmotic flow (EOF) without electrolytic additives. In general,
      flow was found to be equal to or greater than flow with typical CE buffer
      systems. The magnitude of EOF was determined for each solvent by open tubular
      capillary electrophoresis (CE) and related to viscosity (eta), dielectric
      constant (epsilon), and the ratio of dielectric constant to viscosity
      (eta/epsilon). Zeta potentials (zeta) were derived indirectly from flow data and
      tabulated. Comparisons of flow behavior and zeta were made between pure solvents
      and conventional CE buffers, and questions of equilibrium and reproducibility
      were addressed. Similar experiments were performed using hydroorganic mobile
      phases (ACN/water, MeOH/water) across the complete compositional range (100%
      water-100% organic), with flow characteristics and zeta reported for each mobile
      phase system. Packed capillary columns (5-microns ODS) were evaluated for flow
      and retention stability under capillary electrochromatographic (CEC) conditions.
      A separation of 11 polycyclic aromatic hydrocarbons was performed in under 13 min
      by CEC with an ACN/water mobile phase. Reduced plate heights (h) were calculated
      between 2.5 and 3.0 for solutes with capacity factors (k') up to 4.5 for the most
      retained solute.

PMID- 9271068
TI  - Baker's yeast biomass (Saccharomyces cerevisae) for selective on-line trace
      enrichment and liquid chromatography of polar pesticides in water.
AB  - Baker's yeast cells (Saccharomices cerevisae) were successfully immobilized onto
      silica gel and used in the on-line isolation and trace enrichment of
      desisopropylatrazine, desethylatrazine, hydroxyatrazine, simazine, cyanazine,
      atrazine, carbaryl, propanil, linuron, and fenamiphos. Since humic and fulvic
      acids were not coextracted, no cleanup was necessary. The pesticides were spiked
      at 0.1-1 microgram L-1 in tap water, groundwater, and seawater and were
      preconcentrated using on-line solid-phase extraction into a yeast immobilized on
      silica gel precolumn followed by liquid chromatography with diode array
      detection. All the variables that affect the enrichment step, such as amount of
      yeast immobilized, dimensions of the precolumn, sample pH, and preconcentration
      flow rate, were optimized. The degree of selectivity was evaluated by comparing
      the chromatograms obtained after on-line sample preconcentration on the yeast
      precolumn with those obtained by on-line solid-phase extraction using a precolumn
      filled with C18 material. The relative standard deviation for the whole procedure
      in the determination of the selected pesticides at the 0.3 microgram L-1
      concentration level ranged from 1 to 9%, depending on the pesticide and the type
      of water. Detection limits within the range 0.01-0.5 microgram L-1 were obtained
      by percolating only 25 mL of water sample without any additional cleanup step.

PMID- 9271069
TI  - Measuring column void volumes with NMR.
AB  - A novel method for measuring resin porosities and column void volumes with
      fluorine. NMR has not been developed. In situ measurements of the void volumes
      accessible to an array of fluorinated probe molecules are used to characterize
      the pore size distribution of the media. Application of this simple procedure is
      demonstrated for a commercially packed column and several bulk resins. The
      porosity distributions obtained by this technique are similar to those obtained
      by size exclusion chromatography. Unlike chromatographic tracer studies, however,
      this method does not require packed columns.

PMID- 9271070
TI  - Determination of the metabolites of the herbicide dimethyl
      tetrachloroterephthalate in drinking water by high-performance liquid
      chromatography with gas chromatography/mass spectrometry confirmation.
AB  - Two metabolites of the herbicide dimethyl tetrachloroterephthalate, (DCPA),
      monomethyl tetrachloroterephthalate (MM) and tetrachloroterephthalic acid (TCPA),
      are assayed via high-performance liquid chromatography with ion paring. Samples
      are analyzed via direct injection, without preparation, and analyte detection is
      accomplished with an ultraviolet photodiode array detector. The metabolites are
      extracted from positive samples with a petroleum ether/diethyl ether mixture,
      derivatized with N,O-bis(trimethylsilyl) trifluoracetamide, and confirmed by way
      of gas chromatography/mass spectrometry. The HPLC analysis of 200 spiked drinking
      water samples yielded a recovery range of 92-106% with a mean recovery of 101%
      for TCPA and a recovery range of 92-101% with a mean recovery of 96% for MM. The
      minimum detection limits for TCPA and MM were 2.4 and 2.7 micrograms/L,
      respectively. In addition, the GC/MS analysis of spiked reagent water yielded
      mean recoveries of 91% for MM and 86% for TCPA. Twenty drinking water samples
      were split and analyzed by the HPLC and GC/MS methods and by USEPA Method 515.1.
      Comparable results were obtained. The HPLC method, which is amenable to
      automation, typically allows for the analysis of up to 40 samples overnight.

PMID- 9271071
TI  - On-line detection of nonspecific protein adsorption at artificial surfaces.
AB  - A detailed understanding of the interaction of proteins with artificial surfaces
      is essential for many applications in medicine and biochemistry. The affinity of
      surfaces toward proteins may, for instance, remove pharmacological proteins from
      media or control the adherence of pathogenic bacteria to protheses. Only a few
      analytical techniques now exist that can be used to study the binding process in
      real time, using unlabeled proteins. By investigating the adsorption kinetics of
      fibrinogen at differently terminated self-assembled monolayers (SAMs) of
      alkanethiols on thin gold films, it is demonstrated that acoustic plate-mode
      sensors are a promising analytical tool for studying the adsorption of proteins.
      In agreement with previous studies for fibrinogen, it is shown in situ that
      hexa(ethylene glycol)-terminated SAMs (HS(CH2)11 (OCH2CH2)6OH) exhibit very low
      protein adsorption and that methyl-terminated SAMs (HS(CH2)11CH3) tend to absorb
      large amounts of protein nonspecifically. The observed adsorption kinetics
      deviate from classical Langmuir behavior; these kinetics are compatible with a
      mechanism that involves an unfolding of fibrinogen after adsorption. Film quality
      is controlled by IR, XPS, and contact angle measurements.

PMID- 9271072
TI  - Scintillator light source for chemical sensing in the near-ultraviolet.
AB  - A novel chemical sensor based on a light source composed of a radionuclide and a
      scintillator is experimentally evaluated. Proper selection of a
      radionuclide/scintillator combination permits fabrication of a practical light
      source emitting in the ultraviolet (UV). Such a UV light source is critical for
      chemical sensors which utilize UV-excitable chromophores or fluorophores. Unlike
      conventional gas-filled discharge lamps, the developed UV source is compact,
      inexpensive, simple in design, stable, and highly reliable, and it does not
      require an external power source. The utility of the new source was demonstrated
      through construction of sensors for oxygen. This application was selected for
      experimental evaluation of the new light source since oxygen sensors have been
      characterized well with conventional light sources. Although the scintillator
      light source is less intense than conventional sources, its excellent short- and
      long-term stability provides a reproducibility of fluorescence measurements of
      about 0.35% RSD. The stability of the scintillator light source suggests its
      utility in simple single-beam detection configurations.

PMID- 9271073
TI  - Sensing antimonite and arsenite at the subattomole level with genetically
      engineered bioluminescent bacteria.
AB  - A highly sensitive and selective optical sensing system for antimonite has been
      developed using genetically engineered bacteria. The basis of this system is the
      ability of certain bacteria to survive in environments that are contaminated with
      antimonite, arsenite, and arsenate. The survival is conferred to the bacteria by
      the ars operon, which consists of five genes that code for three structural
      proteins, ArsA, ArsB, and ArsC, and two regulatory proteins, ArsD and ArsR. ArsA,
      ArsB, and ArsC form a protein pump system that extrudes antimonite, arsenite, and
      arsenate once these anions reach the cytoplasm of the bacterium. A method was
      developed for monitoring antimonite and arsenite by using a single plasmid that
      incorporates the regulatory gene of the extrusion system, arsR, and the genes of
      bacterial luciferase, luxA and luxB. In the designed plasmid, ArsR regulates the
      expression of bacterial luciferase in a manner that is dependent on the
      concentration of antimonite and arsenite in the sample. Thus, the bioluminescence
      emitted by luciferase can be related to the concentration of antimonite and
      arsenite in the sample. Concentrations for antimonite and arsenite in the order
      of 10(-5) M, which corresponds to subattomole levels, can be detected. This
      bacterial-based sensing system is highly selective for antimonite and arsenite.

PMID- 9271075
TI  - ADP-ribosylation-factor-regulated phospholipase D activity localizes to secretory
      vesicles and mobilizes to the plasma membrane following N-formylmethionyl-leucyl
      phenylalanine stimulation of human neutrophils.
AB  - Phospholipase D (PLD) is responsible for the hydrolysis of phosphatidylcholine to
      produce phosphatidic acid and choline. Human neutrophils contain PLD activity
      which is regulated by the small GTPases, ADP-ribosylation factor (ARF) and Rho
      proteins. In this study we have examined the subcellular localization of the ARF
      regulated PLD activity in non-activated neutrophils and cells 'primed' with N
      formylmethionyl-leucyl-phenylalanine (fMetLeuPhe). We report that PLD activity is
      localized at the secretory vesicles in control cells and is mobilized to the
      plasma membrane upon stimulation with fMetLeuPhe. We conclude that the ARF
      regulated PLD activity is translocated to the plasma membrane by secretory
      vesicles upon stimulation of neutrophils with fMetLeuPhe in inflammatory/priming
      doses. We propose that this relocalization of PLD is important for the subsequent
      events occurring during neutrophil activation.

PMID- 9271074
TI  - Kinetoplastid glucose transporters.
AB  - Protozoa of the order kinetoplastida have colonized many habitats, and several
      species are important parasites of humans. Adaptation to different environments
      requires an associated adaptation at a cell's interface with its environment,
      i.e. the plasma membrane. Sugar transport by the kinetoplastida as a
      phylogenetically related group of organisms offers an exceptional model in which
      to study the ways by which the carrier proteins involved in this process may
      evolve to meet differing environmental challenges. Seven genes encoding proteins
      involved in glucose transport have been cloned from several kinetoplastid
      species. The transporters all belong to the glucose transporter superfamily
      exemplified by the mammalian erythrocyte transporter GLUT1. Some species, such as
      the African trypanosome Trypanosoma brucei, which undergo a life cycle where the
      parasites are exposed to very different glucose concentrations in the mammalian
      bloodstream and tsetse-fly midgut, have evolved two different transporters to
      deal with this fluctuation. Other species, such as the South American trypanosome
      Trypanosoma cruzi, multiply predominantly in conditions of relative glucose
      deprivation (intracellularly in the mammalian host, or within the reduviid bug
      midgut) and have a single, relatively high-affinity type, transporter. All of the
      kinetoplastid transporters can also transport d-fructose, and are relatively
      insensitive to the classical inhibitors of GLUT1 transport cytochalasin B and
      phloretin.

PMID- 9271076
TI  - A critical amino acid residue, asp446, in UDP-glucuronosyltransferase.
AB  - An amino acid residue, Asp446, was found to be essential for the enzymic activity
      of UDP-glucuronosyltransferase (UGT). We obtained a rat phenol UGT (UGT1*06) cDNA
      (named Ysh) from male rat liver by reverse-transcription (RT)-PCR using pfu
      polymerase. A mutant Ysh having two different bases, A1337G and G1384A (named Ysh
      A1337GC1384A), that result in two amino acid substitutions, D446G and V462M, was
      obtained by RT-PCR using Taq polymerase. Ysh was expressed functionally in
      microsomes of Saccharomyces cerevisiae strain AH22. However, the expressed
      protein from YshA1337GG1384A had no transferase activity. Two other mutant cDNAs
      with YshA1337G having one changed base, A1337G, resulting in one amino acid
      substitution, D446G, and YshG1384A having a changed base, G1384A, resulting in an
      amino acid substitution, V462M, were constructed and expressed in the yeast. The
      expressed protein from YshG1384A (named YshV462M) exhibited enzymic activity, but
      the one from YshA1337G (named YshD446G) did not show any activity at all. Asp446
      was conserved in all UGTs and UDP-galactose:ceramide galactosyltransferases
      reported, suggesting that Asp446 plays a critical role in each enzyme.

PMID- 9271077
TI  - Evidence for the existence of a pristanoyl-CoA oxidase gene in man.
AB  - In the rat, 2-methyl branched fatty acids and the bile acid intermediates di- and
      tri-hydroxycoprostanic acids are desaturated by pristanoyl-CoA oxidase and
      trihydroxycoprostanoyl-CoA oxidase respectively. In the human, these compounds
      are oxidized by a single enzyme, branched-chain acyl-CoA oxidase, which according
      to its amino acid sequence is the human homologue of rat trihydroxycoprostanoyl
      CoA oxidase. Pristanoyl-CoA oxidase is apparently absent from human tissues as
      indicated by immunoblot analysis [Van Veldhoven, Van Rompuy, Fransen, de Bethune
      and Mannaerts (1994) Eur. J. Biochem. 222, 795-801] and Northern-blot analysis
      [Vanhooren, Fransen, de Bethune, Baumgart, Baes, Torrekens, Van Leuven, Mannaerts
      and Van Veldhoven (1996) Eur. J. Biochem. 239, 302-309] of human tissues. In this
      paper we present evidence, however, that at least the gene for pristanoyl-CoA
      oxidase is present in the human. A human liver cDNA encoding a protein of 700
      amino acids, showing 75% amino acid identity with rat pristanoyl-CoA oxidase and
      harbouring a peroxisomal C-terminal-targeting signal (SKL), was isolated.
      Bacterial expression of the cDNA resulted in a fusion protein that was cross
      reactive with antibodies directed against rat pristanoyl-CoA oxidase and the C
      terminal SKL sequence. Screening of a genomic library with the isolated cDNA as a
      probe resulted in a genomic clone in which four introns were localized. By means
      of fluorescence in situ hybridization the gene for human pristanoyl-CoA oxidase
      was mapped at chromosome position 4p15.3. We conclude that a gene for pristanoyl
      CoA oxidase is present in the human genome. The gene appears to be expressed to
      such a low extent in liver that its mRNA cannot be detected by routine Northern
      blot analysis and that its product remains undetected by standard immunoblotting
      or by enzyme activity measurements. We speculate that the gene may be expressed
      under special (e.g. certain developmental stages) conditions or in certain
      specialized tissues not examined thus far.

PMID- 9271078
TI  - Analysis of the endoplasmic reticular Ca2+ requirement for alpha1-antitrypsin
      processing and transport competence.
AB  - Depletion of Ca2+ sequestered within the endoplasmic reticulum (ER) of HepG2
      hepatoma cells results in the luminal accumulation of immature alpha1-antitrypsin
      possessing Man8-9 GlcNAc2 oligosaccharide side chains. This study explores the
      basis for this arrest and describes consequent alterations in the size and rate
      of secretion of the complex endoglycosidase H-resistant form of the protein.
      Inhibition of glucosidase I and II with castanospermine or alpha-1,2-mannosidase
      with 1-deoxymannojirimycin produced altered ER processing intermediates that were
      rapidly secreted. Subsequent mobilization of ER Ca2+ stores resulted in the
      appearance and retention of slightly larger related forms of these intermediates.
      Retention of glycosylated intermediates was not ascribable to an association with
      alpha1,2-mannosidase or lectin-like chaperones, the intermediates were not
      degraded and all evidence of ER retention or size alterations produced by Ca2+
      depletion was quickly reversed by Ca2+ restoration. Cells that were Ca2+ depleted
      for 2 h slowly secreted an abnormal slightly smaller complex oligosaccharide form
      of alpha1-antitrypsin at approximately the same rate as the non-glycosylated
      protein generated by treatment with tunicamycin. The hypothesis that Ca2+ affects
      the folding and ER transport competence of glycosylated forms of alpha1
      antitrypsin is discussed.

PMID- 9271079
TI  - Peptidyl inverse esters of p-methoxybenzoic acid: a novel class of potent
      inactivator of the serine proteases.
AB  - A series of novel synthetic peptides, containing a C-terminal beta-amino alcohol
      linked to p-methoxybenzoic acid via an ester linkage, have been prepared and
      tested as inhibitors against typical members of the serine protease family. For
      example, the sequences Ac-Val-Pro-NH-CH-(CH2-C6H5)-CH2O-CO-C6H4-OCH3 (I) and Ac
      Val-Pro-NH-CH-[CH-(CH3)2]-CH2O-CO-C6H4-OCH3 (II), which fulfil the known primary
      and secondary specificity requirements of chymotrypsin and elastase respectively,
      have been found to behave as exceptionally potent irreversible inactivators of
      their respective target protease. Thus I was found to inactivate chymotrypsin
      with an overall second-order rate constant (k2/Ki) of approx. 6.6x10(6) M-1. s-1,
      whereas II is an even more potent inactivator of human neutrophil elastase,
      exhibiting a second-order rate constant of inactivation of approx. 1.3x10(7) M
      1.s-1. These values represent the largest rate constants ever reported for the
      inactivation of these proteases with synthetic peptide-based inactivators. On
      prolonged incubation in substrate-containing buffers, samples of the inactivated
      proteases were found to regain activity slowly. The first-order rate constants
      for the regeneration of enzymic activity from chymotrypsin and human neutrophil
      elastase inactivated by I and II respectively were determined to be approx.
      5.8x10(-5) s-1 and approx. 4.3x10(-4) s-1. We believe that the most likely
      mechanism for the inactivation and regeneration of enzymic activity involves the
      formation and subsequent slow hydrolysis of long-lived acyl enzyme intermediates.

PMID- 9271081
TI  - Biosynthesis of mycothiol: elucidation of the sequence of steps in Mycobacterium
      smegmatis.
AB  - Several members of the Actinomycetales, including the medically important
      mycobacteria, produce 1-D-myo-inosityl-2-(N-acetyl-L-cysteinyl)amino-2-deoxy
      alpha-D- glucop yranoside (trivial name mycothiol) as their principal low
      molecular-mass thiol. The pseudo-disaccharide component of mycothiol, 1-D-myo
      inosityl-2-amino-2-deoxy-alpha-D-glucopyranoside (alpha-D-GI), was synthesized by
      ligation of 1-D,L-2,3,4,5, 6-penta-O-acetyl-myo-inositol to 3,4,6-tri-O-acetyl-2
      deoxy- 2-(2,4-dinitrophenylamino)-alpha-D-glu- copyranosyl bromide to give, in
      the first instance, an isomeric mixture of alpha- and beta-linked pseudo
      disaccharides. The alpha-coupled D,D and D,L isomers, alpha-D-GI and alpha-L-GI
      respectively, were purified from the mixture by TLC, followed by removal of the
      protecting groups. A cell-free extract of Mycobacterium smegmatis catalysed the
      ligation of cysteine, acetate and alpha-D-GI in the presence of ATP and Mg2+ to
      form mycothiol, as judged by HPLC. When no acetate was added to the incubation
      mixture, an additional thiol accumulated. In the presence of [14C]acetate no
      radiolabel was recovered in this species, but only in mycothiol. The additional
      thiol was isolated as the bimane derivative, and 1H and 1H-1H COSY NMR spectra
      confirmed its identity as desacetylmycothiol. A more complete conversion of
      desacetylmycothiol into mycothiol was achieved in the presence of acetyl-S-CoA.
      These results indicate that the biosynthesis of mycothiol proceeds by the
      sequential addition of cysteine and acetate to alpha-D-GI. The inositol moiety
      appears to be an important determinant of specificity, since alpha-L-GI was
      poorly utilized.

PMID- 9271080
TI  - Interleukin-6 is necessary, but not sufficient, for induction of the humanC
      reactive protein gene in vivo.
AB  - We have investigated the involvement of interleukin-6 (IL-6) in the induction of
      the gene encoding the acute-phase protein human C-reactive protein (hCRP). In
      transgenic mice the hCRP gene can be induced by lipopolysaccharide (LPS), but not
      by IL-6. In contrast, hCRP was inducible by IL-6 in primary human hepatocytes and
      in primary hepatocytes isolated from transgenic mice. To further evaluate the
      role of IL-6, we introduced the hCRP transgene into animals lacking endogenous IL
      6 (IL-6-negative mice). Here, hCRP was not inducible by LPS, but was induced by a
      combination of LPS and IL-6. These results clearly demonstrate that IL-6 is
      necessary, but not sufficient, for the induction of hCRP expression. These animal
      models will allow further dissection of the cytokine network responsible for the
      regulation of the major human acute-phase reactant CRP.

PMID- 9271082
TI  - Role of Ca2+ and protein kinase C in the receptor-mediated activation of Na+/H+
      exchange in isolated liver cells.
AB  - This work aimed to study the relationship between agonist-induced changes in
      cytosolic free calcium levels, protein kinase C (PKC) activity and intracellular
      pH in isolated liver cells. We observed that, like alpha1-adrenergic agonists,
      the Ca2+-mobilizing vasoactive peptides vasopressin and angiotensin II produced
      an extracellular-Na+-dependent, 5-(N-ethyl-N-isopropyl)amiloride-sensitive,
      intracellular alkalinization, indicative of Na+/H+ antiporter activation.
      Blocking the agonist-induced increase in the intracellular Ca2+ concentration
      using the calcium chelator bis-(o-aminophenoxy)ethane-N,N,N', N'-tetra-acetic
      acid (BAPTA) prevented all types of receptor-mediated intracellular
      alkalinization. Thus activation of the Na+/H+ exchanger by either alpha1
      adrenergic agonists or vasoactive peptides relies on the mobilization of
      intracellular Ca2+. In contrast, only the alpha1-adrenergic-agonist-induced
      alkalinization was dependent on extracellular Ca2+. Even though alpha1-adrenergic
      as well as vasoactive peptide agonists stimulated protein kinase C (PKC) activity
      in isolated liver cells, only the alpha1-adrenoreceptor-mediated intracellular
      alkalinization was dependent on PKC. According to these observations, Ca2+
      mobilizing agonists appear to activate the Na+/H+ exchanger by at least two
      different mechanisms: (1) the alpha1-adrenoreceptor-mediated activation that is
      dependent on extracellular Ca2+ and PKC; and (2) vasoactive-peptide-induced
      alkalinization that is independent of extracellular Ca2+ and PKC. The alpha1
      adrenoreceptor-mediated, PKC-sensitive, activation of the Na+/H+ exchanger seems
      to be responsible for the distinct ability of these receptors to elicit the
      sustained stimulation of hepatic functions.

PMID- 9271083
TI  - Characterization of the intracellular signalling pathways that underlie growth
      factor-stimulated glucose transport in Xenopus oocytes: evidence for ras- and rho
      dependent pathways of phosphatidylinositol 3-kinase activation.
AB  - The stimulation of glucose transport is one of the early cellular responses to
      growth factors and is essential for cell proliferation, yet the molecular
      processes that underlie this response are poorly defined. The aim of this study
      was to characterize the role of the low-molecular-mass G-proteins, Ras and Rho,
      and their downstream targets, Raf protein kinase and phosphatidylinositol 3
      kinase, in the regulation of glucose transport in Xenopus oocytes by two distinct
      growth-factor receptors: the insulin-like growth factor I (IGF-I) tyrosine kinase
      receptor and the heterotrimeric G-protein-coupled lysophosphatidic acid (LPA)
      receptor. Microinjection of a neutralizing anti-Ras antibody partially blocked
      IGF-I-stimulated deoxyglucose uptake but was without effect on LPA-stimulated
      deoxyglucose uptake. In contrast, microinjection of the C3 coenzyme of botulinum
      toxin, which selectively ADP-ribosylates and inactivates Rho, inhibited LPA
      stimulated, but not IGF-I-stimulated, deoxyglucose uptake. Similarly, LPA- but
      not IGF-I-stimulated deoxyglucose uptake was attenuated in oocytes expressing a
      dominant negative rho construct. Cells expressing a dominant negative mutant of
      Raf protein kinase exhibited markedly reduced sensitivity to both LPA and IGF-I,
      consistent with a role for endogenous Raf in glucose uptake by both growth
      factors. Furthermore, expression of a constitutively activated form of raf-1
      resulted in a growth-factor-independent increase in deoxyglucose uptake.
      Measurements of phosphatidylinositol 3-kinase activity in microinjected cells
      support the hypothesis that the IGF-I receptor stimulates glucose transport by a
      Ras-dependent activation of phosphatidylinositol 3-kinase, whereas the G-protein
      coupled LPA receptor controls this response by a pathway that involves Rho
      dependent activation of a distinct phosphatidylinositol 3-kinase. Thus we provide
      evidence for clear differences in the signalling pathways that control glucose
      transport by G-protein-coupled and tyrosine kinase growth-factor receptors.
      Furthermore this is the first demonstration that active Rho is involved in the
      signalling pathways that regulate glucose uptake in response to some growth
      factors.

PMID- 9271084
TI  - Molecular characterization and expression of Onchocerca volvulus glutathione
      reductase.
AB  - Glutathione metabolism represents a potential target for anti-parasite drug
      design. The central role of glutathione reductase (GR) in maintenance of the
      thiol redox state and in anti-oxidative defence has to be evaluated in more
      detail in order to establish the essential function of this enzyme for the
      survival of the filarial parasite Onchocerca volvulus. The O. volvulus GR (OvGR)
      gene was cloned and sequenced. The gene is composed of 13 exons and 12 introns
      and spans 4065 bp. The first intron is located within the 5'-untranslated region
      of the gene, 16 nucleotides upstream of the translation initiation codon.
      Southern-blot analysis and structural characterization of the genomic sequence
      indicate that OvGR is encoded by a single-copy gene. Isolation of various cDNA
      clones revealed a polymorphism of polyadenylation initiation with no consensus
      polyadenylation sites in any of the cDNAs analysed. The entire cDNA is 1977 bp
      long and carries the nematode-specific spliced leader sequence SL1 at its 5' end,
      236 nucleotides upstream of the first in-frame methionine. The cDNA codes for a
      polypeptide of 462 amino acids with 53.5% sequence identity with human GR (HsGR).
      A total of 18 out of 19 residues contributing to glutathione binding are
      identical in OvGR and HsGR. However, one of the arginine residues (Arg-224 in
      HsGR) involved in discrimination between NADPH and NADH in all known GRs is
      substituted by tryptophan (Trp-207 in OvGR). The coding region of OvGR was
      expressed in Escherichia coli as a histidine-fusion protein, and it was
      established that the parasite protein still favours the binding of NADPH (Km 10.9
      microM) over NADH (Km 108 microM). The histidine-fusion protein has a subunit
      size of 54 kDa and is active as a homodimer of 110 kDa.

PMID- 9271085
TI  - Accumulation of pro-apolipoprotein A-II in mouse senile amyloid fibrils.
AB  - Apolipoprotein A-II (apoA-II), the major apoprotein of serum high-density
      lipoprotein, is deposited as amyloid fibrils (AApoAII) in murine senile
      amyloidosis. We have identified and purified a more basic amyloid protein from
      old-mouse liver. N-terminal sequencing of the protein revealed that the pro
      segment of five amino acid residues (Ala-Leu-Val-Lys-Arg) extended from the N
      terminal glutamine residue of mature apoA-II protein. MS analysis revealed the
      deposit of intact pro-apoA-II protein (molecular mass 9319 Da). Antiserum was
      prepared for staining of the AApoAII amyloid deposition. The relative abundance
      of pro-apoA-II to mature apoA-II in the amyloid-fibril fraction isolated from
      livers of mice with severe amyloidosis was 14.1%. The similar abundance of pro
      apoA-II in the amyloid fibril fraction from the spleen (16.3%) suggested that
      deposited pro-apoA-II originated from the blood. The concentration of pro-apoA-II
      was much lower in the serum (1.5% of mature apoA-II) than in the amyloid-fibril
      fraction. There was no difference in the content of pro-apoA-II between the
      amyloidogenetic R1.P1-Apoa2c and amyloid-resistant SAMR1 strains at the age of 3
      months. The abundance of pro-apoA-II in the amyloid-fibril fraction compared with
      the serum suggested that it plays a key role in the initialization of mouse
      senile amyloidosis.

PMID- 9271086
TI  - Effect of adenine nucleotides on myo-inositol-1,4,5-trisphosphate-induced calcium
      release.
AB  - The effects of a whole series of adenine nucleotides on Ins(1,4,5)P3-induced Ca2+
      release were characterized in permeabilized A7r5 smooth-muscle cells. Several
      adenine nucleotides activated the Ins(1, 4,5)P3 receptor. It was observed that 3'
      phosphoadenosine 5'-phosphoulphate, CoA, di(adenosine-5')tetraphosphate (Ap4A)
      and di(adenosine-5')pentaphosphate (Ap5A) were more effective than ATP. Ap4A and
      Ap5A also interacted with a lower EC50 than ATP. In order to find out how these
      adenine nucleotides affected Ins(1,4, 5)P3-induced Ca2+ release, we have measured
      their effect on the response of permeabilized A7r5 cells to a progressively
      increasing Ins(1,4,5)P3 concentration. Stimulatory ATP and Ap5A concentrations
      had no effect on the threshold Ins(1,4,5)P3 concentration for initiating Ca2+
      release, but they stimulated Ca2+ release in the presence of supra-threshold
      Ins(1,4,5)P3 concentrations by increasing the co-operativity of the release
      process. Inhibition of the Ins(1,4,5)P3-induced Ca2+ release at higher ATP
      concentrations was associated with a further increase in co-operativity and also
      with a shift in threshold towards higher Ins(1,4,5)P3 concentrations. ATP had no
      effect on the non-specific Ca2+ leak in the absence of Ins(1,4,5)P3. We conclude
      that the adenine-nucleotide-binding site can be activated by many different
      adenine nucleotides. Binding of these compounds to the transducing domain of the
      Ins(1,4,5)P3 receptor increases the efficiency of transmitting Ins(1,4,5)P3
      binding to channel opening. The inhibition by high ATP concentrations is exerted
      at a different site, related to Ins(1,4,5)P3 binding.

PMID- 9271088
TI  - Direct ESR detection or peroxynitrite-induced tyrosine-centred protein radicals
      in human blood plasma.
AB  - Peroxynitrite, the reaction product of O2.- and .NO, is a toxic compound involved
      in several oxidative processes that modify proteins. The mechanisms of these
      oxidative reactions are not completely understood. In this study, using direct
      ESR at 37 degrees C, we observed that peroxynitrite induced in human blood plasma
      a long-lived singlet signal at g = 2.004 arising from proteins. This signal was
      not due to a specific plasma protein, because several purified proteins were able
      to form a peroxynitrite-induced g = 2.004 signal, but serum albumin and IgG
      showed the most intense signals. Hydroxyurea, a tyrosyl radical scavenger,
      strongly inhibited the signal, and horseradish peroxidase/H2O2, a radical
      generating system known to induce tyrosyl radicals, induced a similar signal.
      Furthermore peptides containing a Tyr in the central portion of the molecule were
      able to form a stable peroxynitrite-dependent g = 2.004 signal, whereas peptides
      in which Tyr was substituted with Gly, Trp or Phe and peptides with Tyr at the N
      terminus or near the C-terminus did not form radicals that were stable at 37
      degrees C. We suggest that Tyr residues are at least the major radical sources of
      the peroxynitrite-dependent g = 2.004 signal at 37 degrees C in plasma or in
      isolated proteins. Although significantly enhanced by CO2/bicarbonate, the signal
      was detectable in whole plasma at relatively high peroxynitrite concentrations
      (>2 mM) but, after removal of ascorbate or urate or in dialysed plasma, it was
      detectable at lower concentrations (100-1000 microM). Our results suggest that
      the major role of ascorbate and urate is to reduce or 'repair' the radical(s)
      centred on Tyr residues and not to scavenge peroxynitrite (or
      nitrosoperoxycarbonate, the oxidant formed in CO2-containing fluids). This
      mechanism of inhibition by plasma antioxidants may be a means of preserving the
      physiological functions of peroxynitrite.

PMID- 9271087
TI  - Involvement of glucokinase translocation in the mechanism by which resorcinol
      inhibits glycolysis in hepatocytes.
AB  - Proglycosyn and resorcinol stimulate glycogen synthesis and inhibit glycolysis in
      hepatocytes. The former effect is attributed to inactivation of phosphorylase
      mediated by glucuronidated metabolites. This study investigated the mechanism by
      which resorcinol inhibits glycolysis. Resorcinol (150 microM) inhibited
      glycolysis in hepatocytes incubated with glucose (15-35 mM) but not with
      dihydroxyacetone (10 mM). The inhibition of glycolysis at elevated glucose
      concentration was associated with inhibition of glucose-induced dissociation of
      glucokinase and aldolase. The resorcinol concentration that caused half-maximal
      inhibition (20-43 microM) increased with increasing glucose concentration (15-35
      mM). Resorcinol inhibited the translocation of glucokinase and the stimulation of
      detritiation of [2-3H]glucose and [3-3H]glucose caused by sorbitol (10-200
      microM), but it potentiated the stimulation of glycogen synthesis. The inhibition
      of glycolysis by resorcinol could not be accounted for by diversion of substrate
      to glycogen. The glucose 6-phosphate content correlated with the free glucokinase
      activity. Resorcinol counteracted the increase in glucose 6-phosphate and
      fructose 2,6-bisphosphate caused by elevated glucose concentration or by
      sorbitol. The suppression of glucose 6-phosphate at high glucose concentration
      (15-35 mM) could be explained by the low activity of free glucokinase. However,
      the suppression at 5 mM glucose was due in part to an independent mechanism. The
      effect of resorcinol on glucokinase translocation was partly counteracted by
      galactosamine, which suppresses UDP-glucose and inhibits glucuronide formation,
      and was mimicked by phenol and p-nitrophenol but not by p-nitrophenylglucuronide.
      It is concluded that resorcinol inhibits glycolysis at elevated glucose
      concentration or when stimulated by sorbitol through increased glucokinase
      binding. The results indicate a link between glucuronidation and glucokinase
      translocation.

PMID- 9271089
TI  - Haemolytic activity of stonustoxin from stonefish (Synanceja horrida) venom: pore
      formation and the role of cationic amino acid residues.
AB  - Stonustoxin (SNTX) is a two-subunit protein toxin purified from the venom of the
      stonefish (Synanceja horrida), which induces potent haemolytic activity. We
      examined the pore-forming property of this non-enzymic protein by an osmotic
      protection assay. SNTX-induced haemolysis was completely prevented by osmotic
      protectants of adequate size [poly(ethylene) glycol 3000; molecular diameter
      approx. 3.2 nm]. Uncharged molecules of smaller size, such as raffinose and
      poly(ethylene) glycol 1000-2000, failed to protect against cell lysis. These
      findings indicate that SNTX induces the formation of hydrophilic pores in the
      cell membrane, which results in the lysis of erythrocytes. Since cationic
      residues contribute significantly to the cytolytic activity of several other pore
      forming toxins, we examined the role of positively charged lysine and arginine
      residues in the haemolytic activity of SNTX. SNTX lost its haemolytic activity
      when the positively charged side chains of lysine residues were neutralized or
      converted into negatively charged side chains upon carbamylation or succinylation
      respectively. The haemolytic activity of SNTX was also inhibited by the
      modification of positively charged arginine residues using 2,3-butanedione. The
      loss of haemolysis showed strong correlation with the number of Lys or Arg
      residues modified. CD analyses, however, showed that the conformation of SNTX was
      not significantly affected by these chemical modifications. Further, the
      haemolytic activity of SNTX was competitively inhibited by various negatively
      charged lipids, such as phosphatidylserine, cardiolipin and
      monosialogangliosides. These results indicate that SNTX induces potent haemolytic
      activity through the formation of pores in the cell membrane, and that cationic
      residues play a crucial role in its cytolytic mechanism.

PMID- 9271090
TI  - Evidence for the formation of a heterotrimeric complex of leukaemia inhibitory
      factor with its receptor subunits in solution.
AB  - Leukaemia inhibitory factor (LIF) is a polyfunctional cytokine that is 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. Human LIF
      binds with unusually high affinity to a naturally occurring mouse soluble LIF
      receptor alpha-chain, and this property was used to purify a stable complex of
      human LIF and mouse LIF receptor alpha-chain from pregnant-mouse serum.
      Recombinant soluble human gp130 was expressed, with a FLAG(R) epitope (DYKDDDDK)
      at the N-terminus, in the methylotropic yeast Pichia pastoris and purified using
      affinity chromatography. The formation of a trimeric complex in solution was
      established by native gel electrophoresis, gel-filtration chromatography,
      sedimentation equilibrium analysis, surface plasmon resonance spectroscopy and
      chemical cross-linking. The stoichiometry of this solution complex was 1:1:1, in
      contrast with that of the complex of interleukin-6, the interleukin-6-specific
      low-affinity receptor subunit and gp130, which is 2:2:2.

PMID- 9271091
TI  - The arachidonate-activatable, NADPH oxidase-associated H+ channel is contained
      within the multi-membrane-spanning N-terminal region of gp91-phox.
AB  - The generation of superoxide by the NADPH oxidase of neutrophils is accompanied
      by the efflux of H+ ions through a H+ channel. gp91-phox, a protein component of
      the oxidase, has been shown previously to function as a H+ channel [Henderson,
      Banting and Chappell (1995) J. Biol. Chem. 270, 5909-5916]. We have constructed a
      CHO cell line (CHO-N) that expresses an N-terminal fragment of gp91-phox
      containing the predicted multiple transmembrane domains of the protein. These
      cells exhibit H+ fluxes in response to an imposed proton motive force and in the
      presence of arachidonate (to open the channel). The H+ fluxes were
      indistinguishable from those observed in cells expressing full-length gp91-phox.
      Therefore the N-terminal 230 amino acids of gp91-phox contain all that is
      required to function as the NADPH oxidase-associated H+ channel.

PMID- 9271092
TI  - Perturbation of the antigen-binding site and staphylococcal protein A-binding
      site of IgG before significant changes in global conformation during
      denaturation: an equilibrium study.
AB  - Although conformational perturbation of the active sites of many enzymes has been
      reported to precede global molecular conformational changes [Tsou (1993) Science
      262, 380-381], little effort has been made to compare the susceptibility of the
      ligand-binding site of proteins and the protein molecules as a whole to
      perturbation by denaturants. Immunoglobulin is chosen in this study to address
      this problem. It is found that the variable and constant regions (Fv and Fc) of a
      monoclonal antibody of an IgG subclass against adenylate kinase lose their
      abilities to bind antigen and staphylococcal Protein A after treatment with
      guanidinium chloride concentrations considerably lower than those required to
      change the global conformation of the antibody as a whole, as detected by
      fluorescence and second-derivative UV absorption spectroscopy. These results
      indicate that both ligand-binding sites of the antibody concerned are more
      fragile than the molecule as a whole and that the Fv and Fc regions of the
      antibody molecule unfold sequentially during denaturation.

PMID- 9271093
TI  - Calcium-binding properties of human erythrocyte calpain.
AB  - The results presented provide more information on the sequential mechanism that
      promotes the Ca2+-induced activation of human erythrocyte mu-calpain under
      physiological conditions. The primary event in this process corresponds to the
      binding of Ca2+ to eight interacting sites, of which there are four in each of
      the two calpain subunits. Progressive binding of this metal ion is linearly
      correlated with the dissociation of the proteinase, which reaches completion when
      all eight binding sites are occupied. The affinity for Ca2+ in the native
      heterodimeric calpain is increased 2-fold in the isolated 80 kDa catalytic
      subunit, but it reaches a Kd consistent with the physiological concentration of
      Ca2+ only in the active autoproteolytically derived 75 kDa form. Binding of Ca2+
      in physiological conditions, and thus the formation of the 75 kDa subunit, can
      occur only in the presence of positive modulators. These are represented by the
      natural activator protein, found to be a Ca2+-binding protein, and by highly
      digestible substrates. The former produces a very large increase in the affinity
      of calpain for Ca2+, and the latter a smaller but still consistent decrease in
      the Kd of the proteinase for the metal ion. As a result, both dissociation into
      the constituent subunits and the autoproteolytic conversion of the native 80 kDa
      subunit into the active 75 kDa form can occur within the physiological
      fluctuations in Ca2+ concentration. The delay in the expression of the
      proteolytic activity with respect to Ca2+ binding to native calpain, no longer
      detectable in the 75 kDa form, can be attributed to a Ca2+-induced functional
      conformational change, which is correlated with the accessibility of the active
      site of the enzyme.

PMID- 9271094
TI  - Identification and characterization of two distinct intracellular GLUT4 pools in
      rat skeletal muscle: evidence for an endosomal and an insulin-sensitive GLUT4
      compartment.
AB  - In skeletal muscle, acute insulin treatment results in the recruitment of the
      GLUT4 glucose transporter from intracellular vesicular structures to the plasma
      membrane. The precise nature of these intracellular GLUT4 stores has, however,
      remained poorly defined. Using an established skeletal-muscle fractionation
      procedure we present evidence for the existence of two distinct intracellular
      GLUT4 compartments. We have shown that after fractionation of crude muscle
      membranes on a discontinuous sucrose gradient the majority of the GLUT4
      immunoreactivity was largely present in two sucrose fractions (30 and 35%, w/w,
      sucrose; denoted F30 and F35 respectively) containing intracellular membranes of
      different buoyant densities. Here we show that these fractions contained 44+/-6
      and 49+/-7% of the crude membrane GLUT4 reactivity respectively, and could be
      further discriminated on the basis of their immunoreactivity against specific
      subcellular antigen markers. Membranes from the F30 fraction were highly enriched
      in transferrin receptor (TfR) and annexin II, two markers of the early endosome
      compartment, whereas they were significantly depleted of both GLUT1 and the
      alpha1-subunit of (Na++K+)-ATPase, two cell-surface markers. Insulin treatment
      resulted in a significant reduction in GLUT4 content in membranes from the F35
      fraction, whereas the amount of GLUT4 in the less dense (F30) fraction remained
      unaffected by insulin. Immunoprecipitation of GLUT4-containing vesicles from both
      intracellular fractions revealed that TfR was present in GLUT4 vesicles isolated
      from membranes from the F30 fraction. In contrast, GLUT4 vesicles from the F35
      fraction were devoid of TfR. The aminopeptidase, vp165, was present in GLUT4
      vesicles from both F30 and F35; however, vesicles isolated from F30 contained
      over twice as much vp165 per unit of GLUT4 than those isolated from F35. The
      biochemical co-localization of vp165/GLUT4 was further substantiated by double
      immunogold labelling of ultrathin muscle sections. Overall, our data indicate the
      presence of at least two internal GLUT4 pools: one possibly derived from an
      endosomal recycling compartment, and the other representing a specialized insulin
      sensitive GLUT4 storage pool. Both pools contain vp165.

PMID- 9271095
TI  - Up-regulation of the levels of expression and function of a constitutively active
      mutant of the hamster alpha1B-adrenoceptor by ligands that act as inverse
      agonists.
AB  - The alpha1-adrenergic agonist phenylephrine stimulated phospholipase D (PLD)
      activity in Rat 1 fibroblasts transfected to express either the wild-type hamster
      alpha1B-adrenoceptor or a constitutively active mutant (CAM) form of this
      receptor. The EC50 for agonist stimulation of PLD activity was substantially
      lower at the CAM receptor than at the wild-type receptor as previously noted for
      phenylephrine stimulation of phosphoinositidase C activity. Sustained treatment
      of cells expressing the CAM alpha1B-adrenoceptor with phentolamine resulted in a
      marked up-regulation in levels of this receptor with half-maximal effects
      produced within 24 h and with an EC50 of approx. 40 nM. Such an up-regulation
      could be produced with a range of other ligands generally viewed as alpha1
      adrenoceptor antagonists but equivalent treatment of cells expressing the wild
      type alpha1B-adrenoceptor was unable to mimic these effects. After sustained
      treatment of the CAM alpha1B-adrenoceptor expressing cells with phentolamine,
      basal PLD activity was increased and phenylephrine was now able to stimulate PLD
      activity to greater levels than in vehicle-treated CAM alpha1B-adrenoceptor
      expressing cells. The EC50 for phenylephrine stimulation of PLD activity was not
      altered, however, by phentolamine pretreatment and the associated up-regulation
      of the receptor. After phentolamine-induced up-regulation of basal PLD activity,
      a range of alpha1-antagonists were shown to possess the characteristics of
      inverse agonists of the CAM alpha1B-adrenoceptor as they were able to
      substantially decrease the elevated basal PLD activity.

PMID- 9271097
TI  - Functional role of a distal (3'-phosphate) group of CoA in the recombinant human
      liver medium-chain acyl-CoA dehydrogenase-catalysed reaction.
AB  - The X-ray crystallographic structure of medium-chain acyl-CoA dehydrogenase
      (MCAD)-octenoyl-CoA complex reveals that the 3'-phosphate group of CoA is
      confined to the exterior of the protein structure [approx. 15 A (1.5 nm) away
      from the enzyme active site], and is fully exposed to the outside solvent
      environment. To ascertain whether such a distal (3'-phosphate) fragment of CoA
      plays any significant role in the enzyme catalysis, we investigated the
      recombinant human liver MCAD (HMCAD)-catalysed reaction by using normal (phospho)
      and 3'-phosphate-truncated (dephospho) forms of octanoyl-CoA and butyryl-CoA
      substrates. The steady-state kinetic data revealed that deletion of the 3'
      phosphate group from octanoyl-CoA substrate increased the turnover rate of the
      enzyme to about one-quarter, whereas that from butyryl-CoA substrate decreased
      the turnover rate of the enzyme to about one-fifth; the Km values of both these
      substrates were increased by 5-10-fold on deletion of the 3'-phosphate group from
      the corresponding acyl-CoA substrates. The transient kinetics for the reductive
      half-reaction, oxidative half-reaction and the dissociation 'off-rate' (of the
      reaction product from the oxidized enzyme site) were all found to be affected by
      deletions of the 3'-phosphate group from octanoyl-CoA and butyryl-CoA substrates.
      A cumulative account of these results reveals that, although the 3'-phosphate
      group of acyl-CoA substrates might seem 'useless' on the basis of the structural
      data, it has an essential functional role during HMCAD catalysis.

PMID- 9271096
TI  - A novel murine P-450 gene, Cyp4a14, is part of a cluster of Cyp4a and Cyp4b, but
      not of CYP4F, genes in mouse and humans.
AB  - Genomic clones for Cyp4a12 and a novel member of the murine Cyp4a gene family
      were isolated. The novel gene, designated Cyp4a14, has a GC rich sequence
      immediately 5' of the transcription start site, and is similar to the rat CYP4A2
      and CYP4A3 genes. The Cyp4a14 gene spans approximately 13 kb, and contains 12
      exons; sequence similarity to the rat CYP4A2 gene sequence falls off 300 bp
      upstream from the start site. In view of the known sex-specific expression of the
      rat CYP4A2 gene, the expression and inducibility of Cyp4a14 was examined. The
      gene was highly inducible in the liver when mice were treated with the peroxisome
      proliferator, methylclofenapate; induction levels were low in control animals and
      no sex differences in expression were observed. By contrast, the Cyp4a12 RNA was
      highly expressed in liver and kidney of control male mice but was expressed at
      very low levels in liver and kidney of female mice. Testosterone treatment
      increased the level of this RNA in female liver slightly, and to a greater extent
      in the kidney of female mice. In agreement with studies on the cognate RNA,
      expression of Cyp4a12 protein was male-specific in the liver of control mice and
      extremely high inducibility of Cyp4a10 protein, with no sex differences, was also
      demonstrated. In view of the overlapping patterns of inducibility of the three
      Cyp4a genes, we investigated whether the three genes were co-localized in the
      genome. Two overlapping yeast artificial chromosome (YAC) clones were isolated,
      and the three Cyp4a genes were shown to be present on a single YAC of 220 kb. The
      Cyp4a genes are adjacent to the Cyp4b1 gene, with Cyp4a12 most distant from
      Cyp4b1. The clustering of these two gene subfamilies in the mouse was replicated
      in the human, where the CYPA411 and CYP4B1 genes were present in a single YAC
      clone of 440 kb. However, the human CYP4F2 gene was mapped to chromosome 19.
      Phylogenetic analysis of the CYP4 gene families demonstrated that CYP4A and CYP4B
      are more closely related than CYP4F.

PMID- 9271098
TI  - Subcellular localization and purification of a p-hydroxyphenylpyruvate
      dioxygenase from cultured carrot cells and characterization of the corresponding
      cDNA.
AB  - p-Hydroxyphenylpyruvate dioxygenase catalyses the transformation of p
      hydroxyphenylpyruvate into homogentisate. In plants this enzyme has a crucial
      role because homogentisate is the aromatic precursor of all prenylquinones.
      Furthermore this enzyme was recently identified as the molecular target for new
      families of potent herbicides. In this study we examine precisely the
      localization of p-hydroxyphenylpyruvate dioxygenase activity within carrot cells.
      Our results provide evidence that, in cultured carrot cells, p
      hydroxyphenylpyruvate dioxygenase is associated with the cytosol. Purification
      and SDS/PAGE analysis of this enzyme revealed that its activity is associated
      with a polypeptide of 45-46 kDa. This protein specifically cross-reacts with an
      antiserum raised against the p-hydroxyphenylpyruvate dioxygenase of Pseudomonas
      fluorescens. Gel-filtration chromatography indicates that the enzyme behaves as a
      homodimer. We also report the isolation and nucleotide sequence of a cDNA
      encoding a carrot p-hydroxyphenylpyruvate dioxygenase. The nucleotide sequence
      (1684 bp) encodes a protein of 442 amino acid residues with a molecular mass of
      48094 Da and shows specific C-terminal regions of similarity with other p
      hydroxyphenylpyruvate dioxygenases. This cDNA encodes a functional p
      hydroxyphenylpyruvate dioxygenase, as evidenced by expression studies with
      transformed Escherichia coli cells. Comparison of the N-terminal sequence of the
      45-46 kDa polypeptide purified from carrot cells with the deduced peptide
      sequence of the cDNA confirms that this polypeptide supports p
      hydroxyphenylpyruvate dioxygenase activity. Immunodetection studies of the native
      enzyme in carrot cellular extracts reveal that N-terminal proteolysis occurs
      during the process of purification. This proteolysis explains the difference in
      molecular masses between the purified protein and the deduced polypeptide.

PMID- 9271099
TI  - Parallel changes in nuclear and cytosolic calcium in mouse pancreatic beta-cells.
AB  - In the neuroendocrine pancreatic beta-cell, elevations in intracellular Ca2+ lead
      to insulin secretion and the initiation of gene transcription. However, the
      relationship between cytosolic and nuclear Ca2+ in these cells is unknown. The
      Ca2+ permeability of the nuclear membrane would therefore determine if Ca2+ could
      play a direct role in Ca2+-dependent nuclear processes. Using confocal
      fluorescence microscopy with the ratiometric Ca2+ indicator indo-1 and carefully
      correcting for compartmentalized indicator, we now demonstrate that there is no
      difference between the nuclear Ca2+ concentration and the cytosolic Ca2+
      concentration ([Ca2+]c) in the resting beta-cell. Slow Ca2+ oscillations induced
      by glucose, fast oscillations induced by glucagon-like peptide-1 and responses to
      potassium and carbachol all indicate that changes in cytosolic Ca2+ are reflected
      within the nucleus. We conclude that there are no restrictions on Ca2+ entry into
      the nucleus of the pancreatic beta-cell subsequent to increases in [Ca2+]c. This
      implies that any signal involved in increasing [Ca2+]c, and thereby insulin
      release, may also promote nuclear Ca2+-induced gene transcription.

PMID- 9271100
TI  - Nramp1 locus encodes a 65 kDa interferon-gamma-inducible protein in murine
      macrophages.
AB  - The murine Nramp1 (natural-resistance-associated macrophage protein) locus,
      formerly known as Ity/Lsh/Bcg, was isolated previously on the basis of
      chromosomal location, and as conferring natural resistance to infection against
      intracellular macrophage pathogens. The gene encodes a transporter molecule of
      unknown function. We have prepared polyclonal antisera against the C-terminal 35
      amino acids of murine Nramp1. This serum is reactive towards a 65 kDa protein,
      expressed in murine macrophage cells from resistant or susceptible mice
      stimulated with interferon-gamma and lipopolysaccharide, but not in non
      macrophage cells. Evidence indicates that Nramp1 is localized in a subcellular
      membrane rather than at the cell surface. This evidence includes: the
      identification of conserved endocytic targeting motifs following inspection of
      human and murine Nramp sequences; the enrichment of Nramp1, following magnetic
      selection of phagolysosomal vesicles from activated macrophages that were allowed
      to phagocytose magnetic, IgG-coated beads; confocal microscopy. These studies
      place Nramp1 on a membrane in close proximity to obligate intracellular
      pathogens. A link between Nramp1 and divalent-cation transport is suggested by
      sequence similarity with yeast SMF1. Evidence showing modulation of Nramp1
      protein levels by iron chelation provides a direct link with Nramp1 function and
      divalent-cation metabolism.

PMID- 9271101
TI  - Modulation of protein kinase C by endogenous sphingosine: inhibition of phorbol
      dibutyrate binding in Niemann-Pick C fibroblasts.
AB  - The abnormal and variable increase in levels of free sphingoid bases recently
      described in fibroblasts from Niemann-Pick C patients allowed us to investigate
      the modulation of protein kinase C in vivo by endogenous sphingosine. The
      specific binding of [20-3H]phorbol 12, 13-dibutyrate to the regulatory domain of
      membrane-bound protein kinase C was significantly decreased in fibroblasts from
      patients compared with controls. A pronounced difference between the two groups
      (P<0.0001) was demonstrated in low-density lipoprotein-supplemented medium, i.e.
      under conditions known to disclose abnormal mobilization of unesterified
      cholesterol in Niemann-Pick C fibroblasts. Furthermore the degree of impairment
      of [3H]phorbol 12,13-dibutyrate binding was highly correlated (r=0.95) with the
      sphingosine levels measured in fibroblasts from those patients. Scatchard
      analysis of the binding data indicated that Niemann-Pick C and control
      fibroblasts contained almost the same number of binding sites per cell. A 8-34
      fold increase in Kd was measured in Niemann-Pick C fibroblasts with at least a 5
      fold increase in sphingosine levels. Removal, by cell fractionation, of membrane
      bound protein kinase C from the bulk of sphingosine induced a normalization of Kd
      values. The overall results suggest that protein kinase C inhibition is directly
      related to sphingosine accumulation.

PMID- 9271102
TI  - Neural regulation of the formation of skeletal muscle phosphorylase kinase
      holoenzyme in adult and developing rat muscle.
AB  - Neural influences on the co-ordination of expression of the multiple subunits of
      skeletal muscle phosphorylase kinase and their assembly to form the holoenzyme
      complex, alpha4beta4gamma4delta4, have been examined during denervation and re
      innervation of adult skeletal muscle and during neonatal muscle development.
      Denervation of the tibialis anterior and extensor digitorum longus muscles of the
      rat hindlimb was associated with a rapid decline in the mRNA for the gamma
      subunit, and an abrupt decrease in gamma-subunit protein. The levels of the alpha
      and beta-subunit proteins in the denervated muscles also declined rapidly, their
      time course of reduction being similar to that for the gamma-subunit protein, but
      they did not decrease to the same extent. In contrast with the rapid decline in
      gamma-subunit mRNA upon denervation, alpha- and beta-subunit mRNAs stayed at
      control innervated levels for approx. 8-10 days, but then decreased rapidly.
      Their decline coincided very closely with the onset of re-innervation. Re
      innervation of the denervated muscles, which occurs rapidly and uniformly after
      the sciatic nerve crush injury, produced an eventual slow and prolonged recovery
      of the mRNA for all three subunits and parallel increases in each of the subunit
      proteins. A similar co-ordinated increase of both subunit mRNA and subunit
      proteins of the phosphorylase kinase holoenzyme was observed during neonatal
      muscle development, during the period when the muscles were attaining their adult
      pattern of motor activity. The phosphorylase kinase holoenzyme remains in a non
      activated form during all of these physiological changes, as is compatible with
      the presence of the full complement of the regulatory subunits. These data are
      consistent with a model whereby the transcriptional and translational expression
      of phosphorylase kinase gamma subunit occurs only with concomitant expression of
      the alpha and beta subunits. This would ensure that free and unregulated,
      activated gamma subunit alone, which would give rise to unregulated
      glycogenolysis, is not produced. The data also suggest that control of
      phosphorylase kinase subunit expression and the formation of the holoenzyme in
      skeletal muscle is provided by the motor nerve, probably through imposed levels
      or patterns of muscle activity.

PMID- 9271104
TI  - Inhibition of the membrane protein PC-1 by commercial acidic fibroblast growth
      factor is due to a non-protein contaminant.

PMID- 9271103
TI  - Cell stress-induced phosphorylation of ATF2 and c-Jun transcription factors in
      rat ventricular myocytes.
AB  - Ventricular myocytes are exposed to various pathologically important cell
      stresses in vivo. In vitro, extreme stresses (sorbitol-induced hyperosmotic shock
      in the presence or absence of okadaic acid, and anisomycin) were applied to
      ventricular myocytes cultured from neonatal rat hearts to induce a robust
      activation of the 46 and 54 kDa stress-activated protein kinases (SAPKs). These
      activities were increased in nuclear extracts of cells in the absence of any net
      import of SAPK protein. Phosphorylation of ATF2 and c-Jun was increased as shown
      by the appearance of reduced-mobility species on SDS/PAGE, which were sensitive
      to treatment with protein phosphatase 2A. Hyperosmotic shock and anisomycin had
      no effect on the abundance of ATF2. In contrast, cell stresses induced a greater
      than 10-fold increase in total c-Jun immunoreactivity detected on Western blots
      with antibody to c-Jun (KM-1). Cycloheximide did not inhibit this increase, which
      we conclude represents phosphorylation of c-Jun. This conclusion was supported by
      use of a c-Jun(phospho-Ser-73) antibody. Immunostaining of cells also showed
      increases in nuclear phospho-c-Jun in response to hyperosmotic stress. Severe
      stress (hyperosmotic shock+okadaic acid for 2 h) induced proteins (migrating at
      approx. 51 and 57 kDa) that cross-reacted strongly with KM-1 antibodies in both
      the nucleus and the cytosol. These may represent forms of c-Jun that had
      undergone further modification. These studies show that stresses induce
      phosphorylation of transcription factors in ventricular myocytes and we suggest
      that this response may be pathologically relevant.

PMID- 9271105
TI  - The Saccharomyces cerevisiae MFS superfamily SGE1 gene confers resistance to
      cationic dyes.
AB  - A gene from Saccharomyces cerevisiae whose overexpression confers resistance to
      10-N-nonyl acridine orange (NAO) has been isolated. This cationic dye binds
      acidic phospholipids and more specifically cardiolipin (Petit, J. M., Maftah, A.,
      Ratinaud, M. H. and Julien, R. Eur. J. Biochem. 209, 267-273, 1992). The isolated
      gene was found to be identical to SGE1, a partial multicopy suppressor of the
      gal11 mutation (Amakasu, H., Suzuki, Y., Nishizawa, M. and Fukasawa, T. Genetics
      134, 675-683, 1993), that also confers crystal violet resistance to a
      supersensitive strain (Ehrenhofer-Murray, A. E., Wurgler, F. E. and Sengstag, C.
      Mol. Gen. Genet. 244, 287-294, 1994). The data presented in this paper show that
      the SGE1 gene product, a member of the major facilitator superfamily, confers a
      pleiotropic drug-resistance phenotype when present in high copy number. The
      results also demonstrate that Sge1p acts as an extrusion permease whose
      specificity seems restricted to dye molecules possessing a large unsaturated
      domain that stabilizes a permanent positive charge such as NAO, crystal violet,
      ethidium bromide or malachite green.

PMID- 9271106
TI  - Stationary-phase gene expression in Saccharomyces cerevisiae during wine
      fermentation.
AB  - Genetic engineering of wine yeast strains requires the identification of gene
      promoters specifically activated under wine processing conditions. In this study,
      transcriptional activation of specific genes was followed during the time course
      of wine fermentation by quantifying mRNA levels in a haploid wine strain of
      Saccharomyces cerevisiae grown on synthetic or natural winery musts. Northern
      analyses were performed using radioactive probes from 19 genes previously
      described as being expressed under laboratory growth conditions or on molasses in
      S. cerevisiae during the stationary phase and/or under nitrogen starvation. Nine
      genes, including members of the HSP family, showed a transition-phase induction
      profile. For three of them, mRNA transcripts could be detected until the end of
      the fermentation. Expression of one of these genes, HSP30, was further studied
      using a HSP30::lacZ fusion on both multicopy and monocopy expression vectors. The
      production of beta-galactosidase by recombinant cells was measured during cell
      growth and fermentation on synthetic and natural winery musts. We showed that the
      HSP30 promoter can induce high gene expression during late stationary phase and
      remains active until the end of the wine fermentation process. Similar expression
      profiles were obtained on five natural winery musts.

PMID- 9271107
TI  - GCR1-dependent transcriptional activation of yeast retrotransposon Ty2-917.
AB  - Transcription of Saccharomyces cerevisiae Ty2-917 retrotransposon depends on
      regulatory elements both upstream and downstream of the transcription initiation
      site. An upstream activation sequence (UAS) and a downstream enhancer stimulate
      transcription synergistically. Here we show that activation by both of these
      sites depends on the GCR1 product, a transcription factor which also regulates
      the genes encoding yeast glycolytic enzymes. Eliminating GCR1 causes a 100-fold
      decrease in transcription of Ty2-917. Activation by the isolated Ty2-917 UAS also
      strongly depends on GCR1. Unexpectedly, GCR1-dependent activation by the Ty2-917
      enhancer is strongly position-dependent. Activation by the enhancer in its normal
      position within the transcription unit depended strongly on GCR1, but eliminating
      GCR1 reduced activation only three-fold when the enhancer was moved upstream of
      the transcribed region. Gel mobility shift and DNaseI protection assays indicated
      that GCR1 binds specifically to multiple sites within the Ty2-917 UAS and
      enhancer regions.

PMID- 9271108
TI  - Surface properties of top- and bottom-fermenting yeast.
AB  - The surface physico-chemical properties (hydrophobicity, electrophoretic
      mobility, chemical composition) of a large set of top- and bottom-fermenting
      brewing yeasts, harvested in the exponential and stationary growth phases, have
      been investigated. Bottom- and top-fermenting strains showed different surface
      properties. Top strains were generally more hydrophobic than bottom strains, due
      to higher surface protein concentrations. Bottom strains possessed higher surface
      phosphate concentrations. The different profiles of electrophoretic mobility
      versus pH for top and bottom strains could be explained by modelling the surface
      charge according to the surface chemical composition as given by X-ray
      photoelectron spectroscopy. For bottom strains, the electrical properties were
      mainly controlled by phosphate, resulting in a low isoelectric point (pH 2 or
      below) and an electrophoretic mobility that did not become much more negative
      above pH 4. For the top strains, they were mainly determined by the balance of
      protonated amino- and carboxylate groups in proteins, which gave a high
      isoelectric point (pH 4) and an electrophoretic mobility changing greatly with pH
      in the range of 2 to 7. No difference in surface properties was found between
      flocculating and non-flocculating strains, or between cells from the exponential
      and stationary growth phases, even for strains where flocculation occurred during
      the transition from one growth phase to the other.

PMID- 9271109
TI  - Phytopathogenic filamentous (Ashbya, Eremothecium) and dimorphic fungi (Holleya,
      Nematospora) with needle-shaped ascospores as new members within the
      Saccharomycetaceae.
AB  - Phylogenetic relationships between species from the genera Kluyveromyces and
      Saccharomyces and representatives of the Metschnikowiaceae (Holleya,
      Metschnikowia, Nematospora) including the two filamentous phytopathogenic fungi
      Ashbya gossypii and Eremothecium ashbyii were studied by comparing the
      monosaccharide pattern of purified cell walls, the ubiquinone system, the
      presence of dityrosine in ascospore walls, and nucleotide sequences of ribosomal
      DNA (complete 18S rDNA, ITS1 and ITS2 region). Based on sequence information from
      both ITS regions, the genera Ashbya, Eremothecium, Holleya and Nematospora are
      closely related and may be placed in a single genus as suggested by Kurtzman
      (1995; J Industr. Microbiol. 14, 523-530). In a phylogenetic tree derived from
      the ITS1 and ITS2 region as well as in a tree derived from the complete 18S rDNA
      gene, the genus Metschnikowia remains distinct. The molecular evidence from
      ribosomal sequences suggests that morphology and ornamentation of ascospores as
      well as mycelium formation and fermentation should not be used as differentiating
      characters in family delimitation. Our data on cell wall sugars, ubiquinone side
      chains, dityrosine, and ribosomal DNA sequences support the inclusion of plant
      pathogenic, predominantly filamentous genera like Ashbya and Eremothecium or
      dimorphic genera like Holleya and Nematospora with needle-shaped ascospores
      within the family Saccharomycetaceae. After comparison of sequences from the
      complete genes of the 18S rDNA the genus Kluyveromyces appears heterogeneous. The
      type species of the genus, K. polysporus is congeneric with the genus
      Saccharomyces. The data of Cai et al. (1996; Int. J. Syst. Bacteriol. 46, 542
      549) and our own data suggest to conserve the genus Kluyveromyces for a clade
      containing K. marxianius, K. dobzhanskii, K. wickerhamii and K. aestuarii, which
      again can be included in the family Saccharomycetaceae. The phylogenetic age of
      the Metschnikowiaceae and Saccharomycetaceae will be discussed in the light of
      coevolution.

PMID- 9271110
TI  - Isolation and characterization of the KlHEM1 gene in Kluyveromyces lactis.
AB  - The KlHEM1 gene from Kluyveromyces lactis encodes a functional 5-aminolevulinate
      synthase (deltaALA synthase), as confirmed by complementation of a hem1 mutant
      Saccharomyces cerevisiae strain, homology search, and detection of a 2.3 kb
      transcript. The gene is highly homologous to the ScHEM1 gene, and the sequence of
      the promoter region contains a complex combination of putative regulatory
      signals. Some of them are related to phospholipid biosynthesis, glycolytic
      metabolism, and regulation by carbon source. Transcription of KlHEM1 increased
      significantly in response to limited oxygen, and only slightly with the change
      from repressed (glucose) to derepressed conditions (glycerol). The deltaALA
      synthase from K. lactis contains, in the amino-terminal region, two heme
      responsive elements that are not present in the protein from Saccharomyces
      cerevisiae.

PMID- 9271111
TI  - Identification of genes with nutrient-controlled expression by PCR-mapping in the
      yeast Saccharomyces cerevisiae.
AB  - We have used RNA fingerprinting by the mRNA Differential Display technique to
      identify new genes in the yeast Saccharomyces cerevisiae, expression of which is
      controlled by specific nutrient conditions. mRNA was isolated from cells grown on
      glucose medium into exponential and stationary phase, and from cells starved for
      nitrogen on glucose-containing medium. To avoid interference with the large
      number of glucose-repressible genes, a glucose-repression-deficient strain was
      used. Twenty different sets of arbitrary primers chosen at random were used for
      PCR-amplification of reverse transcriptase generated cDNAs, which resulted in six
      highly reproducible gene expression patterns. The validity of the approach was
      confirmed by sequencing PCR products of genes with known expression patterns,
      SUP44/RPS4, CTT1, SSA3, HSP30 and HSP104, and genes with related functions, TEF1
      and TEF3, encoding translation elongation factors. In all cases the specificity
      of the responses was confirmed by Northern blot analysis. The results show that
      the PCR-mapping method is highly useful for the identification of new genes
      expressed under specific conditions in the yeast S. cerevisiae.

PMID- 9271113
TI  - Current awareness on yeast.

PMID- 9271112
TI  - Phylogenetic relationships of fungal cytochromes c.
AB  - The CYC1 gene encoding cytochrome c in the yeast Candida albicans was cloned by
      complementation of a cytochrome c-deficient mutant of Saccharomyces cerevisiae,
      and its DNA sequence was determined. The analysis of the amino acid sequences of
      cytochrome c from 14 fungal species and two isoforms from S. cerevisiae revealed
      sequences unique to fungi, and revealed a phylogenetic relationship with a
      pronounced divergence between Schizosaccharomyces pombe and other ascomycetous
      budding yeast.

PMID- 9271114
TI  - Alpha2p controls donor preference during mating type interconversion in yeast by
      inactivating a recombinational enhancer of chromosome III.
AB  - Homothallic strains of Saccharomyces cerevisiae can change mating type as often
      as every generation by replacing the allele at the MAT locus with a copy of
      mating type information present at one of two storage loci, HML and HMR, located
      on either end of chromosome III. Selection of the appropriate donor locus is
      dictated by a mating type-specific repressor protein, alpha2p: Cells containing
      alpha2p select HMR, whereas those lacking alpha2p select HML. As a repressor
      protein, alpha2p binds to DNA cooperatively with the transcriptional activator
      Mcm1p. Here we show that two alpha2p/Mcm1p-binding sites, DPS1 and DPS2, control
      donor selection. DPS1 and DPS2 are located approximately 30 kb from the left arm
      of chromosome III, well removed from HML, HMR, and MAT. Precise deletion of only
      DPS1 and DPS2 results in random selection of donor loci and in a cells without
      affecting selection in alpha cells. Reciprocally, deletion of only the alpha2p
      binding segments in each of these two sites results in selection of the wrong
      donor loci in alpha cells without affecting preference in a cells. These results
      suggest that Mcm1p, bound to these two sites in the absence of alpha2p, activates
      HML as donor. Binding of alpha2p blocks the ability of Mcm1p bound to DPS1 and
      DPS2 to activate HML, resulting in default selection of HMR as donor. DPS1 and
      DPS2 also regulate expression of several noncoding RNAs, although deletion of at
      least one of these RNA loci does not affect donor preference. This suggests that
      transcriptional activation, rather than transcription of a specific product, is
      the initiating event in activating the left arm of chromosome III for donor
      selection.

PMID- 9271115
TI  - A newly identified DNA ligase of Saccharomyces cerevisiae involved in RAD52
      independent repair of DNA double-strand breaks.
AB  - Eukaryotic DNA ligases are ATP-dependent DNA strand-joining enzymes that
      participate in DNA replication, repair, and recombination. Whereas mammalian
      cells contain several different DNA ligases, encoded by at least three distinct
      genes, only one DNA ligase has been detected previously in either budding yeast
      or fission yeast. Here, we describe a newly identified nonessential Saccharomyces
      cerevisiae gene that encodes a DNA ligase distinct from the CDC9 gene product.
      This DNA ligase shares significant amino acid sequence homology with human DNA
      ligase IV; accordingly, we designate the yeast gene LIG4. Recombinant LIG4
      protein forms a covalent enzyme-AMP complex and can join a DNA single-strand
      break in a DNA/RNA hybrid duplex, the preferred substrate in vitro. Disruption of
      the LIG4 gene causes only marginally increased cellular sensitivity to several
      DNA damaging agents, and does not further sensitize cdc9 or rad52 mutant cells.
      In contrast, lig4 mutant cells have a 1000-fold reduced capacity for correct
      recircularization of linearized plasmids by illegitimate end-joining after
      transformation. Moreover, homozygous lig4 mutant diploids sporulate less
      efficiently than isogenic wild-type cells, and show retarded progression through
      meiotic prophase I. Spore viability is normal, but lig4 mutants appear to produce
      a higher proportion of tetrads with only three viable spores. The mutant
      phenotypes are consistent with functions of LIG4 in an illegitimate DNA end
      joining pathway and ensuring efficient meiosis.

PMID- 9271116
TI  - Null mutation of mCOUP-TFI results in defects in morphogenesis of the
      glossopharyngeal ganglion, axonal projection, and arborization.
AB  - The COUP-TFs are orphan members of the steroid/thyroid hormone receptor
      superfamily. Multiple COUP-TF members have been cloned and they share a high
      degree of sequence homology between species as divergent as Drosophila and
      humans, suggesting a conservation of function through evolution. The COUP-TFs are
      highly expressed in the developing nervous systems of several species examined,
      indicating their possible involvement in neuronal development and
      differentiation. In the mouse, there are two very homologous COUP-TF genes (I and
      II) and their expression patterns overlap extensively. To study the physiological
      function of mCOUP-TFI, a gene-targeting approach was undertaken. We report here
      that mCOUP-TFI null animals die perinataly. Mutant embryos display an altered
      morphogenesis of the ninth cranial ganglion and nerve. The aberrant formation of
      the ninth ganglion is most possibly attributable to extra cell death in the
      neuronal precursor cell population. In addition, at midgestation, aberrant nerve
      projection and arborization were oberved in several other regions of mutant
      embryos. These results indicate that mCOUP-TFI is required for proper fetal
      development and is essential for postnatal development. Furthermore, mCOUP-TFI
      possesses vital physiological functions that are distinct from mCOUP-TFII despite
      of their high degree of homology and extensive overlapping expression patterns.

PMID- 9271117
TI  - Enhanced apoptotic cell death of renal epithelial cells in mice lacking
      transcription factor AP-2beta.
AB  - Expression of AP-2 transcription factors has been detected previously in
      embryonic renal tissues. We show here that AP-2beta -/- mice complete embryonic
      development and die at postnatal days 1 and 2 because of polycystic kidney
      disease. Analyses of kidney development revealed that induction of epithelial
      conversion, mesenchyme condensation, and further glomerular and tubular
      differentiation occur normally in AP-2beta-deficient mice. At the end of
      embryonic development expression of bcl-X(L), bcl-w, and bcl-2 is down-regulated
      in parallel to massive apoptotic death of collecting duct and distal tubular
      epithelia. Addressing the molecular mechanism we show that transfection of AP-2
      into cell lines in vitro strongly suppresses c-myc-induced apoptosis pointing to
      a function of AP-2 in programming cell survival during embryogenesis. The
      position of the human AP-2beta gene was identified at chromosome 6p12-p21.1,
      within a region that has been mapped for autosomal recessive polycystic kidney
      disease (ARPKD). Sequence analyses of ARPKD patients and linkage analyses using
      intragenic polymorphic markers indicate that the AP-2beta gene is located in
      close proximity to but distinct from the ARPKD gene.

PMID- 9271118
TI  - eyelid antagonizes wingless signaling during Drosophila development and has
      homology to the Bright family of DNA-binding proteins.
AB  - In Drosophila, pattern formation at multiple stages of embryonic and imaginal
      development depends on the same intercellular signaling pathways. We have
      identified a novel gene, eyelid (eld), which is required for embryonic
      segmentation, development of the notum and wing margin, and photoreceptor
      differentiation. In these tissues, eld mutations have effects opposite to those
      caused by wingless (wg) mutations. eld encodes a widely expressed nuclear protein
      with a region homologous to a novel family of DNA-binding domains. Based on this
      homology and on the phenotypic analysis, we suggest that Eld could act as a
      transcription factor antagonistic to the Wg pathway.

PMID- 9271119
TI  - An anteroposterior Dorsal gradient in the Drosophila embryo.
AB  - Dorsoventral (DV) patterning of the Drosophila embryo is initiated by a broad
      Dorsal (Dl) nuclear gradient, which is regulated by a conserved signaling pathway
      that includes the Toll receptor and Pelle kinase. We investigate the consequences
      of expressing a constitutively activated form of the Toll receptor, Toll(10b), in
      anterior regions of the early embryo using the bicoid 3' UTR. Localized Toll(10b)
      products result in the formation of an ectopic, anteroposterior (AP) Dl nuclear
      gradient along the length of the embryo. The analysis of both authentic dorsal
      target genes and defined synthetic promoters suggests that the ectopic gradient
      is sufficient to generate the full repertory of DV patterning responses along the
      AP axis of the embryo. For example, mesoderm determinants are activated in the
      anterior third of the embryo, whereas neurogenic genes are expressed in central
      regions. These results raise the possibility that Toll signaling components
      diffuse in the plasma membrane or syncytial cytoplasm of the early embryo. This
      study also provides evidence that neurogenic repressors may be important for the
      establishment of the sharp mesoderm/neuroectoderm boundary in the early embryo.

PMID- 9271120
TI  - Repression of p53-mediated transcription by MDM2: a dual mechanism.
AB  - The oncoprotein MDM2 binds to the activation domain of the tumor suppressor p53
      and inhibits its ability to stimulate transcription. This same region of p53 is
      able to bind several basal transcription factors that appear to be important for
      the transactivation function of p53. It has therefore been suggested that MDM2
      acts to inhibit p53 by concealing its activation domain from the basal machinery.
      Here we present data suggesting that MDM2 possesses an additional inhibitory
      function. Our experiments reveal that in addition to a p53-binding domain, MDM2
      also contains an inhibitory domain that can directly repress basal transcription
      in the absence of p53. By fusing portions of MDM2 to a heterologous DNA-binding
      domain to allow p53-independent promoter recruitment, we have localized this
      inhibitory domain to a region encompassing amino acids 50-222 of MDM2.
      Furthermore, the function of this inhibitory domain does not require the presence
      of either TFIIA or the TAFs. Of the remaining basal factors, both the small
      subunit of TFIIE and monomeric TBP are bound by the MDM2 inhibitory domain. It is
      possible that MDM2 inhibits the ability of the preinitiation complex to
      synthesize RNA through one of these interactions. Our results are consistent with
      a model in which MDM2 represses p53-dependent transcription by a dual mechanism:
      a masking of the activation domain of p53 through a protein-protein interaction
      that additionally serves to recruit MDM2 to the promoter where it directly
      interferes with the basal transcription machinery.

PMID- 9271121
TI  - PPARgamma induces cell cycle withdrawal: inhibition of E2F/DP DNA-binding
      activity via down-regulation of PP2A.
AB  - PPAR gamma is an adipose-selective nuclear hormone receptor that plays a key role
      in the control of adipocyte differentiation. Previous studies indicated that
      activation of ectopically expressed PPAR gamma induces differentiation when cells
      have ceased growth because of confluence. We show here that ligand activation of
      PPAR gamma is sufficient to induce growth arrest in fibroblasts and SV40 large T
      antigen transformed, adipogenic HIB1B cells. Cell cycle withdrawal is accompanied
      by a decrease in the DNA-binding and transcriptional activity of the E2F/DP
      complex, which is attributable to an increase in the phosphorylation of these
      proteins, especially DP-1. This effect is a consequence of decreased expression
      of the catalytic subunit of the serine-threonine phosphatase PP2A. These data
      suggest an important role for PP2A in the control of E2F/DP activity and a new
      mode of cell cycle control in differentiation.

PMID- 9271123
TI  - The response to extracytoplasmic stress in Escherichia coli is controlled by
      partially overlapping pathways.
AB  - The activity of the alternate sigma-factor sigmaE of Escherichia coli is induced
      by several stressors that lead to the extracytoplasmic accumulation of misfolded
      or unfolded protein. The sigmaE regulon contains several genes, including that
      encoding the periplasmic protease DegP, whose products are thought to be required
      for maintaining the integrity of the cell envelope because cells lacking sigmaE
      are sensitive to elevated temperature and hydrophobic agents. Selection of
      multicopy suppressors of the temperature-sensitive phenotype of cells lacking
      sigmaE revealed that overexpression of the lipoprotein NlpE restored high
      temperature growth to these cells. Overexpression of NlpE has been shown
      previously to induce DegP synthesis by activating the Cpx two-component signal
      transduction pathway, and suppression of the temperature-sensitive phenotype by
      NlpE was found to be dependent on the Cpx proteins. In addition, a constitutively
      active form of the CpxA sensor/kinase also fully suppressed the temperature
      sensitive defect of cells lacking sigmaE. DegP was found to be necessary, but not
      sufficient, for suppression. Activation of the Cpx pathway has also been shown to
      alleviate the toxicity of several LamB mutant proteins. Together, these results
      reveal the existence of two partially overlapping regulatory systems involved in
      the response to extracytoplasmic stress in E. coli.

PMID- 9271122
TI  - Mutations in Drosophila DP and E2F distinguish G1-S progression from an
      associated transcriptional program.
AB  - The E2F transcription factor, a heterodimer of E2F and DP subunits, is capable of
      driving the G1-S transition of the cell cycle. However, mice in which the E2F-1
      gene had been disrupted developed tumors, suggesting a negative role for E2F in
      controlling cell proliferation in some tissues. The consequences of disrupting
      the DP genes have not been reported. We screened for mutations that disrupt G1-S
      transcription late in Drosophila embryogenesis and identified five mutations in
      the dDP gene. Although mutations in dDP or dE2F nearly eliminate E2F-dependent G1
      S transcription, S-phase still occurs. Cyclin E has been shown to be essential
      for S-phase in late embryogenesis, but in dDP and dE2F mutants the peaks of G1-S
      transcription of cyclin E are missing. Thus, greatly reduced levels of cyclin E
      transcript suffice for DNA replication until late in development. Both dDP and
      dE2F are necessary for viability, and mutations in the genes cause lethality at
      the late larval/pupal stage. The mutant phenotypes reveal that both genes promote
      progression of the cell cycle.

PMID- 9271125
TI  - Pulsed electrochemical detection of thiols and disulfides following capillary
      electrophoresis.
AB  - Pulsed electrochemical detection (PED) following capillary electrophoresis (CE)
      has been applied to the direct detection of thiocompounds. Both reduced and
      oxidized thiol moieties are detected without the need of derivatization.
      Thiocompounds can be detected over a wide range of pH conditions (i.e., pH 0-14),
      and except for pH, their response is relatively unperturbed by buffer
      composition. Integrated pulsed amperometric detection (IPAD) results in more
      stable baselines, eliminates oxide-induced artifacts, and yields lower limits of
      detection than other PED waveforms. Mass detection limits using optimized IPAD
      waveforms are typically 2 pg (5 fmol) or less. The high selectivity of PED for
      thiocompounds reduces sample preparation and produces simpler electropherograms
      of complex samples containing these biologically significant compounds.

PMID- 9271124
TI  - Sol-gel chemistry-based Ucon-coated columns for capillary electrophoresis.
AB  - A sol-gel chemistry-based novel approach for the preparation of a Ucon-coated
      fused-silica capillary column in capillary electrophoresis is presented. In this
      approach the sol-gel process is carried out inside 25 microm I.D. fused-silica
      capillaries. The sol solution contained appropriate quantities of an alkoxide
      based sol-gel precursor, a polymeric coating material (Ucon), a crosslinking
      reagent, a surface derivatizing reagent, controlled amounts of water and a
      catalyst dissolved in a suitable solvent system. The coating procedure involves
      filling a capillary with the sol solution and allowing the sol-gel process to
      proceed for an optimum period. Hydrolysis of the alkoxide precursor and
      polycondensation of the hydrolyzed products with the surface silanol groups and
      the hydroxy-terminated Ucon molecules lead to the formation of a surface-bonded
      sol-gel coating on the inner walls of the capillary. The thickness of the coated
      film can be controlled by varying the reaction time, coating solution composition
      and experimental conditions. Commercial availability of high purity sol-gel
      precursors (e.g., TEOS 99.999%), the ease of coating, run-to-run and column-to
      column reproducibility, and long column lifetimes make sol-gel coating chemistry
      very much suitable for being applied in analytical microseparations column
      technology. Test samples of basic proteins and nucleotides were used to evaluate
      the column performance. These results show that the sol-gel coating scheme has
      allowed for the generation of bio-compatible surfaces characterized by high
      separation efficiencies in CE. For different types of solutes, the sol-gel coated
      Ucon column consistently provided migration time R.S.D. values of the order of
      0.5%.

PMID- 9271127
TI  - Micellar electrokinetic chromatographic study of the interaction between
      enkephalin peptide analogs and charged micelles.
AB  - The relative hydrophobicity/hydrophilicity of the pentapeptides leucine
      enkephalin (LE), methionine enkephalin (ME) and five analogs, differing in their
      uncharged side chain and/or chirality, was investigated by micellar
      electrokinetic capillary chromatography (MEKC) employing anionic and cationic
      surfactants. The effect of sodium dodecyl sulfate (SDS) concentration on peptide
      mobility was studied at pH 8.8, a value that is well above the peptide
      isoelectric point, to minimize electrostatic interaction with the anionic
      micelles. Similarly, the effect of cetyltrimethylammonium bromide (CTAB) cationic
      micelles on peptide migration was studied at pH 4.1. The migration order from
      MEKC experiments was compared to the peptide hydrophobicity calculated from
      reversed-phase HPLC-derived hydrophobicity coefficients. Although relative
      peptide hydrophobicity was, in general, positively correlated with effective
      electrophoretic mobility, a tryptophan-containing analog showed only weak
      interaction with micelles compared to the less hydrophobic peptides. The
      enkephalins studied were zwitterionic in character from pH 3 to 8, and their
      migration as a function of pH under MEKC conditions demonstrated that
      electrostatic forces were at least as important as hydrophobic interactions in
      pentapeptide-micelle complexation.

PMID- 9271126
TI  - Evaluation of capillary electrophoresis with post-column derivatization and laser
      induced fluorescence detection for the determination of substance P and its
      metabolites.
AB  - A method for the detection of substance P and its metabolites using capillary
      electrophoresis with post-capillary derivatization and laser-induced fluorescence
      detection is described. The post-capillary chemical derivatization system employs
      naphthalene-2,3-dicarboxaldehyde and beta-mercaptoethanol. Two reactor designs
      were evaluated for the determination of substance P and its metabolites. The
      fluorescent spectroscopic properties of the derivatives under optimal separation
      conditions were also examined. The final system was evaluated for the
      investigation of substance P metabolism in brain following perfusion of the
      striatum with substance P using microdialysis sampling.

PMID- 9271128
TI  - Method of analysis of recombinant acidic fibroblast growth factor by capillary
      electrophoresis.
AB  - Fibroblast growth factors are a series of well characterized proteins that have
      intriguing pharmacological properties. Acidic fibroblast growth factor (aFGF)
      recently appeared in the literature for its efficacy in spinal cord repair in
      rats. The protein has proven difficult to analyze by capillary electrophoresis,
      because it has a tendency to unfold, aggregate and precipitate, especially near
      and above physiological temperatures. By studying the turbidity of capillary
      electrophoresis running buffers and aFGF at 50 degrees C, conditions were found
      that stabilize the aFGF solution, thereby allowing the capillary electrophoretic
      separation of the protein from its recombinant production impurities. The buffer
      system employs 50 mM phosphate buffer at pH 2.5 with 0.25%
      hydroxypropylmethylcellulose (HPMC) additive. This system provided the best
      efficiency and selectivity of the systems studied and was developed for
      pharmaceutical purity analysis.

PMID- 9271129
TI  - Dual-enzyme assay of glutamate in single cells based on capillary
      electrophoresis.
AB  - A new dual-enzyme on-column reaction method combined with capillary
      electrophoresis has been developed for determining the glutamate content in
      single cells. Glutamate dehydrogenase and glutamic pyruvic transaminase were used
      to catalyze the glutamate reaction. Detection was based on monitoring the laser
      induced fluorescence of the reaction product NADH, and the measured fluorescence
      intensity was related to the concentration of glutamate in each cell. Glutamate
      dehydrogenase catalyzed the formation of NADH, and glutamic pyruvic transaminase
      drives the glutamate dehydrogenase reaction by removing a reaction product and
      regenerating glutamate. The detection limit of glutamate is down to the 10(-8) M
      level, which is 1 order of magnitude lower than previously reported detection
      limits based on similar detection methods. The mass detection limit of a few
      attomoles is far superior to that of any other reports. Selectivity for glutamate
      is excellent over most amino acids. The glutamate content in single human
      erythrocytes and baby rat brain neurons were determined with this method and the
      results agreed well with literature values.

PMID- 9271130
TI  - Identification of a recombinant synaptobrevin-thioredoxin fusion protein by
      capillary zone electrophoresis using laser-induced fluorescence detection.
AB  - Capillary zone electrophoresis (CZE) was utilized to identify a synaptobrevin
      thioredoxin fusion protein (TSB-51). TSB-51 is a substrate for cleavage by
      botulinum toxin B at the Q(76)-F(77) site. TSB-51 was derivatized with a
      fluorophore, CBQCA [3-(4-carboxy-benzoyl)-2-quinoline-carboxaldehyde], for 4 h at
      room temperature. Optimal conditions for CZE separation of the TSB-51-CBQCA
      complex were determined: buffer (sodium borate), pH (9.0), applied voltage (25
      kV), temperature (25 degrees C) and forward polarity. SDS-PAGE showed that TSB-51
      had a molecular mass of approximately 19 kDa. The protein was transferred to PVDF
      membrane and sequenced by the Edman degradation method verifying the first twelve
      amino acids as SDKIIHLTDDSF. TSB-51 was also collected during CZE separation and
      subsequently sequenced yielding the first three amino acids as SDK. This CZE-LIF
      method coupled with the CBQCA derivatization, fraction collection and Edman
      sequencing allowed for identification of the recombinant protein, a fast
      separation run time and utilization of small volumes of peptide (1.5 ng
      protein/23.6 nl injection). This method will be used for monitoring the
      endopeptidase activity of botulinum toxin B on TSB-51.

PMID- 9271131
TI  - Direct monitoring of prolidase activity in cultured skin fibroblasts using
      capillary electrophoresis.
AB  - Capillary electrophoresis (CE) was used as an alternative to current analysis
      schemes for detecting prolidase activity in erythrocytes and skin fibroblast
      cultures because of its unique selectivity and high resolving power. Kinetic
      measurement of peptide bond hydrolysis was performed using porcine kidney
      prolidase on different substrates (Gly-Pro, Leu-Pro and Ala-Pro) and by following
      the disappearance of the peptide-substrate's peak. The K(m) values obtained were
      in agreement with those previously reported. Interestingly, in the case of Phe
      Pro as the substrate, simultaneous analysis of the product and parent peptide was
      possible, thus showing the superiority of the capillary electrophoresis (CE)
      assay with respect to the standard spectrophotometric method. The application of
      the CE technique to the characterization of prolidase activity in control and
      prolidase-deficient skin cultured fibroblasts was successful. Enzyme activity was
      easily calculated in all controls tested and the K(m) values determined were
      slightly lower than those obtained with the colorimetric reaction, thus
      confirming our assumption that the CE assay shows higher specificity than the
      ninhydrin technique. Our results demonstrate the feasibility of using CE as a
      simple and reliable technique for determining prolidase activity.

PMID- 9271132
TI  - On-the-fly fluorescence lifetime detection of labeled DNA primers.
AB  - The first application of frequency-domain, on-the-fly fluorescence lifetime
      detection to the detection, identification and resolution of fluorescent labeled
      oligonucleotide primers in capillary electrophoresis is presented. These studies,
      which are directed towards the development of four-decay DNA sequencing, employed
      two common sequencing primers, SP6 and M13/pUC. The primers were each tagged by a
      derivative of either fluorescein or BODIPY. Fluorescence emission maxima and
      lifetimes of the free dyes and the labeled primers were determined both in batch
      mode and on-the-fly in capillary electrophoresis. Fluorescence intensity and
      lifetime electropherograms were extracted from dynamic lifetime data that were
      acquired at 0.1-s intervals during the CE separation. Lifetimes were recovered
      using either conventional non-linear least-squares analysis or the self-modeling
      maximum entropy method, which does not require prior knowledge of the system.
      Based on migration time and fluorescence lifetime, peaks could be detected and
      identified, and co-eluting peaks could be resolved. Interference from background
      impurities and scattered light was greatly reduced by the combination of physical
      separation and lifetime resolution.

PMID- 9271133
TI  - Capillary electrophoresis methodology for identification of cancer related gene
      expression patterns of fluorescent differential display polymerase chain
      reaction.
AB  - The mRNA differential display technique is a method for molecular survey and
      analysis of differential gene expression in eukaryotic cells and tissues. We have
      previously described the use of ABI Prism fluorescent technology to specifically
      amplify expressed sequence tags (ESTs) from several different biological
      paradigms. High throughput, fluorescent differential display performed on an
      automated sequencer (ABI 377) has proven to have significant cost cutting and
      time saving attributes compared to that of the radioactive differential display.
      Additionally, fluorescent tagged mRNA specific reverse transcription and PCR
      decreases the number of the inherent artifacts associated with radioactive
      differential display. We report here the application of a capillary
      electrophoresis system (ABI 310) to the identification of fluorescent
      differential display generated EST patterns. RNA samples from human and animal
      breast cancer paradigms were exposed to this technique and analyzed by the ABI
      310 and the ABI 377. GeneScan and Genotyper software applications were used for
      rapid and semi-automated characterization of fluorescently labeled ESTs.
      Automated sample loading and uniform sample electrophoresis are among the main
      advantages of this system which significantly increase the precision and
      reproducibility of fluorescent differential display.

PMID- 9271134
TI  - Examination of band dispersion during size-selective capillary electrophoresis
      separations of DNA fragments.
AB  - Versatile capillary electrophoresis instrumentation that permits the rapid and
      precise translation of a laser fluorometric detection zone along the capillary
      wall has been used to examine the factors which cause band broadening during size
      selective separations of DNA fragments. Separations are performed using
      capillaries containing entangled polymer solutions. The scanning capabilities of
      this instrumentation facilitates the determination of diffusion coefficients
      under static conditions without the need to discontinue and reapply an electric
      field. The ability to rapidly translate the detection zone along the column
      allows the monitoring of the separation at various points along the capillary
      which enables the examination of the sources of band dispersion under kinetic
      conditions. Results from experiments utilizing various concentrations of both
      high and low molecular mass methyl cellulose polymers as sieving media are
      presented. It is shown that axial diffusion, even when adjusted for kinetic
      conditions using the Einstein relationship, does not account for the total
      observed band variance. Possible explanations for this behavior are presented.

PMID- 9271135
TI  - High-speed electrophoretic separation of DNA fragments using a short capillary.
AB  - Capillary electrophoresis using a replaceable gel buffer was applied to the
      separation of DNA fragments. A short effective length capillary (1-2 cm) at low
      electric field allowed the separation of a 20-1000 bp ladder in 1 min. Although
      similar separation speed was achieved with a longer capillary at high field, the
      resolution of larger fragments was degraded. The short effective length
      capillaries were able to separate the wildtype and mutant PCR products of the TGF
      beta1 gene in under 45 s.

PMID- 9271136
TI  - Capillary electrophoresis as an analytical tool for monitoring nicotine in ATF
      regulated tobacco products.
AB  - Tobacco products are classified at different excise tax rates according to the
      Code of Federal Regulations. These include cigars, cigarettes, pipe tobacco, roll
      your-own tobacco, chewing tobacco and snuff. Nicotine is the primary determinant
      of what constitutes a tobacco product from a regulatory standpoint. Determination
      of nicotine, therefore, is of primary importance and interest to ATF. Since
      nicotine is also the most abundant alkaloid found in tobacco, comprising about
      98% of the total alkaloid content, a rapid method for the determination of
      nicotine in ATF regulated products is desirable. Capillary electrophoresis (CE),
      as an analytical technique, is rapidly gaining importance capturing the interest
      of analysts in several areas. The unique and powerful capabilities of CE
      including high resolution and short analysis times, make it a powerful analytical
      tool in the regulatory area as well. Preliminary studies using a 25 mM sodium
      phosphate buffer, pH 2.5 at 260 nm have yielded promising results for the
      analysis of nicotine in tobacco products. Application of an analytical method for
      the determination of nicotine by CE to ATF regulated tobacco products will be
      presented.

PMID- 9271137
TI  - Influence of the inorganic counterion on the chiral micellar electrokinetic
      separation of basic drugs using the surfactant N-dodecoxycarbonylvaline.
AB  - The chiral surfactant N-dodecoxycarbonylvaline (DDCV) has previously been used
      with a sodium counterion in micellar electrokinetic chromatography (MEKC)
      separations of beta-blockers (pindolol, atenolol, metoprolol, acebutolol,
      alprenolol, oxprenolol and propranolol), beta-agonists (N-methylpseudoephedrine,
      pseudoephedrine, ephedrine and norephedrine) and phenolic amino alcohols
      (norphenylephrine, synephrine, octopamine and salbutamol) in this laboratory. In
      the present study, we investigated the effects of three monovalent counterions-
      Li+, Na+ and K+--on the peak shape, efficiency, selectivity and retention of
      these 15 chiral pharmaceutical compounds with DDCV micelles. A much better (more
      symmetrical) peak shape was observed when Li+ was employed, due to a better if
      still imperfect match of analyte and counterion mobilities; average asymmetry
      factors in LiDDCV, NaDDCV, and KDDCV buffers were 1.9, 3.7, and 4.2,
      respectively. An increase in efficiency of 50-100% for hydrophobic solutes and
      over 100% for many hydrophilic solutes was also observed in LiDDCV compared to
      NaDDCV and KDDCV, probably due to enhanced mass transfer. The influence of an
      organic modifier (acetonitrile) in the separation buffer was also studied for the
      LiDDCV, NaDDCV and KDDCV systems. Although a concentration of either 0 or 5%
      acetonitrile resulted in the best enantiomeric resolution for most analytes, the
      most hydrophobic solutes (alprenolol and propranolol) required the addition of 20
      25% ACN. Due to differences in the conductance of Li+, Na+ and K+, the advantage
      of using Li+ as the counterion for anionic DDCV micelles (better peak shape,
      higher efficiency and resolution, with shorter analysis times), although apparent
      for comparisons at a given applied voltage, is more significant when considered
      in the more appropriate context of equivalent Joule heating.

PMID- 9271138
TI  - Micellar electrokinetic chromatography as a generalized alternative to high
      performance liquid chromatography for purity determination of a class of
      investigational antibacterial drugs.
AB  - Micellar electrokinetic chromatography (MEKC) was successfully used to provide
      purity data for a number of oxazolidinone antibacterials. A run buffer of 100 mM
      SDS and 40 mM HEPES (pH 7.5, NaOH) separated fifteen different materials of
      neutral and cationic, anionic or zwitterionic character, usually with
      efficiencies ten-fold of those observed for HPLC. Different HPLC conditions were
      required for compounds with different structural characteristics. While the high
      efficiency and finite migration window of MEKC may allow observation of
      impurities not seen by HPLC, general use of this method for purity screening of
      combinatorial compounds will require micellar solutions tolerant of high amounts
      of organic, in order to accommodate materials of low aqueous solubility.

PMID- 9271139
TI  - Chiral separation of primary amino compounds using a non-chiral crown ether with
      beta-cyclodextrin by capillary electrophoresis.
AB  - A non-chiral crown ether (18-crown-6) along with beta-cyclodextrin (beta-CD) was
      used to achieve enantioselective separations of primary amino compounds in
      capillary electrophoresis. In this new method, the amino group of these compounds
      is protonated in a low pH separation buffer and forms a selective host-guest
      complex with the crown ether (amino compound+18-crown-6). The hydrophobic portion
      of the host-guest complex is then incorporated into the cavity of the beta
      cyclodextrin. The amino compound is sandwiched between the crown ether and the
      cyclodextrin (18-crown-6+amino compound+beta-CD) and thus determines or enhances
      the enantioselective recognition. It is postulated that the formation of this
      sandwich results in a more selective chiral interaction between the molecule and
      beta-cyclodextrin. The chiral recognition is dependent upon the formation of this
      sandwich complex. This method has been used to achieve enantioselectivity of
      primary amino compounds with a wide variety of substitutions.

PMID- 9271140
TI  - Capillary electrophoresis of peptides and proteins at neutral pH in capillaries
      covalently coated with polyethyleneimine.
AB  - Two procedures for the derivatization of the inner wall of fused-silica
      capillaries for the analysis of peptides and proteins by capillary
      electrophoresis (CE) at neutral pH are presented. In the first procedure,
      polyethyleneimine (PEI) is covalently attached to the capillary wall. In the
      second procedure, PEI is additionally cross-linked. We present analysis of
      standard peptides and proteins by CE using the coated capillaries. These coatings
      will have application for the separation of protein complexes at neutral pH,
      prior to analysis by electrospray mass spectrometry.

PMID- 9271141
TI  - Capillary zone electrophoresis and ion-exchange capillary electrochromatography:
      analytical tools for probing the Hanford nuclear site environment.
AB  - Ion-exchange capillary electrochromatography (IE-CEC) is a relatively new
      separation technique based on the combination of ion-exchange chromatographic and
      electrophoretic separation mechanisms. IE-CEC offers both the efficiency of
      capillary electrophoresis and the selectivity and sample capacity of ion-exchange
      chromatography. The utility of the method was examined with I- and IO3-, which
      are common constituents of nuclear wastes at Hanford, Washington and other U.S.
      Department of Energy (DoE) sites, and ReO4-, a surrogate for TcO4-. The
      advantages and limitations of IE-CEC relative to capillary zone electrophoresis
      (CZE) are explored. The chief advantages are increased loading capacity and an
      alternative selectivity to that of CZE, in addition to increased efficiency
      (relative to conventional ion-exchange chromatography). The run-to-run
      reproducibility of IE-CEC, however, was found to be a limitation of the
      technique.

PMID- 9271142
TI  - Micellar electrokinetic capillary chromatography with laser-induced fluorimetric
      detection of amines in beer.
AB  - Capillary electrophoresis with simultaneous ultraviolet absorbance and laser
      induced fluorescence detection is applied to identify and quantify selected
      amines in beer following derivatization with 7-chloro-4-nitrobenzo-2-oxa-1,3
      diazole. Quantitation was performed using the method of standard addition in
      order to avoid pH-dependent variations in the reactivity of the derivatizing
      agent with the added benefit of verifying peak identity. An inexpensive and "easy
      to-use" on-column fiber optic fluorescence detection cell is described and
      implemented in the analysis.

PMID- 9271143
TI  - Determination of tamoxifen and metabolites in serum by capillary electrophoresis
      using a nonaqueous buffer system.
AB  - Tamoxifen (TAM), an antiestrogen, is widely used to treat hormone-dependent
      breast cancer in post-menopausal women. TAM may be used as a chemopreventive
      agent in women of child-bearing age; however, few data exist describing potential
      TAM-induced fetal toxicity. In support of the National Toxicology Program's
      characterization of reproductive and developmental effects of TAM, this work
      describes an analytical technique utilizing capillary electrophoresis (CE) for
      the detection of circulating levels of TAM, N-desmethyltamoxifen (DMT), and 4
      hydroxytamoxifen (4-HT) in maternal rodent serum. Greater than 90% of 3H-labeled
      TAM was extractable from serum using 98:2 hexane-isoamyl alcohol. Optimum
      separation of TAM, DMT, and 4-HT was obtained on a 57 cmx50 microm capillary
      using a nonaqueous buffer system of 1:1 methanol-acetonitrile containing 50 mM
      ammonium acetate and 1% acetic acid. 4-Dimethylaminopyridine was used as internal
      standard. Temperature and voltage were optimized at 40 degrees C and 15 kV,
      respectively. The limit of detection of TAM by UV detection at 214 nm was
      approximately 800 amol. TAM and DMT were confirmed in serum of female rats 4 h
      following a single oral dose of 120 mg/kg. Transplacental exposure of TAM to
      fetal tissue will be evaluated using this technique.

PMID- 9271144
TI  - Analysis of urinary N-acetyl-beta-glucosaminidase by capillary zone
      electrophoresis.
AB  - N-Acetyl-beta-glucosaminidase (NAG), a glycosidase enzyme, present in serum,
      urine and the renal lysosomes is utilized clinically as an early marker for renal
      damage preceding the elevation of both blood urea nitrogen and creatinine. NAG is
      analyzed by CE after incubation of urine samples with the synthetic substrate
      methylumbelliferyl-beta-D-glucosaminide. The reaction mixture is introduced
      directly into the instrument without further treatment. The released reaction
      product, 4-methyl-umbelliferone, is separated at 13.2 kV in a 400 mM borate
      buffer, pH 8.1. Detection was achieved with either ultraviolet absorption or with
      fluorescence. The fluorescence detection was more sensitive and gave cleaner
      electropherograms. The CZE method correlated well with an automated kinetic
      fluorescent assay. 4-Methyl-umbelliferone conjugated to different substrates is
      used in the analysis of many enzymes involved in the inborn errors of metabolism.

PMID- 9271145
TI  - Ketoprofen analysis in serum by capillary electrophoresis.
AB  - A method for the quantification of ketoprofen, a new non-prescription non
      steroidal anti-inflammatory drug, in serum, by capillary zone electrophoresis for
      therapeutic monitoring and emergency toxicology is described. Serum is
      deproteinized with acetonitrile in the presence of an internal standard, to
      remove serum proteins and to induce sample stacking. The migration time was about
      10 min. The assay was linear between 1-10 mg/l without any interferences. The
      method compared well to an HPLC assay. The HPLC afforded a better detection
      limit, but the CE was less expensive to operate. This method demonstrates that
      capillary electrophoresis is a simple and effective method for determination of
      ketoprofen as well as other drugs in human serum at levels close to 1 mg/l.

PMID- 9271146
TI  - Shear stress measured on beds and wheelchairs.
AB  - Local shear is understood to be one of the principal risk factors for the
      development of pressure sores. There is a need for a small deformable sensor that
      can measure the shear force between skin and deformable materials without
      disturbing the shear phenomenon. In the present study a new shear sensor is
      introduced with a contact area of 4.05 cm2. A series of validation experiments
      was performed with ten healthy young subjects. It was demonstrated that with a
      forward-tilted seat, the sum of the local shear forces between skin and sensormat
      is equal to the resultant shear force measured with a force plate. This result
      serves as a validation of the new sensor. The shear values recorded are 4.8 kPa
      in the longitudinal direction and 8.5 kPa in the transversal direction while
      sitting in a wheelchair, and 5.6 kPa in the longitudinal direction and 3.1 kPa in
      the transversal direction on a mattress of a hospital bed, while in sitting
      position in bed.

PMID- 9271147
TI  - Dynamometric assessment of the plantarflexors in hemiparetic subjects: relations
      between muscular, gait and clinical parameters.
AB  - The aims of this study were to investigate, in 16 subjects with hemiparesis, the
      plantarflexor muscle performance of the paretic side and to determine the level
      of the relationships between muscular parameters, clinical measures and gait
      performance. A Biodex dynamometric system was used to evaluate static and dynamic
      torques, power and maximal rate of tension development of the plantarflexor
      muscles. The clinical measures included the Fugl-Meyer assessment (FMA), the "Up
      & Go" test and an evaluation of ankle muscle tone. Velocity, cadence, stride
      length and gait cycle duration were determined for each subject at both
      comfortable and maximal safe speeds using foot contacts and videographic data.
      Results indicated that dynamometric values produced by the hemiparetic subjects
      were reduced in comparison to those reported for healthy subjects. Their torque
      angle curves had a curvilinear shape which indicated pronounced decrease of
      torque for plantarflexion efforts at the beginning of the movement. Torques
      produced at different velocities of testing did not demonstrate significant
      differences (MANOVAs: p > 0.05) but power values were significantly different.
      Results also showed that all the selected muscular parameters (torque, power and
      maximal rate of tension development) were moderately to highly interrelated (0.65
      < r < 0.94; p < 0.01) suggesting that a common factor of muscular performance was
      assessed. Furthermore, the dynamometric data were significantly associated with
      some of the clinical measures (sensation and lower limb motor control scores of
      the FMA) but were not related to the gait variables (Pearson's r < 0.45; p >
      0.05). This last finding suggests that the relationship between plantarflexor
      strength and the level of gait performance in adults with stroke is complex. The
      relationship may be influenced by other factors such as muscular compensations
      within and between limbs and motor control impairments.

PMID- 9271148
TI  - Non-reflex mediated changes in plantarflexor muscles early after stroke.
AB  - The aims of this study were to determine whether changes in the non-reflex
      component of spastic plantarflexors had developed 2 and 4 months after stroke and
      to study their relationship with the level of impairment. One group of adults
      with hemiparesis (HPs) was tested 2 and 4 months after the onset of stroke, and
      data were compared with a control group (CTLs) tested once. Twenty-two patients
      (14 males) admitted over a 4-month period in a rehabilitation centre (mean = 62
      yrs +/- 14), and 11 (6 males) non-disabled (CTLs) subjects (mean = 57yrs +/-
      12.8) agreed to participate in the study. The resistive torque (RT) recorded with
      a myometer during slow (8-10 degrees/s) passive dorsiflexions imposed manually
      served as the primary outcome, whereas, the Ashworth score (spasticity), ankle
      ROM and Fugl-Meyer motor subscore were used as secondary measures to determine
      the level of impairment. The mean RT values measured at 0 degrees dorsiflexion on
      the affected and unaffected sides were compared with those in CTLs. As expected,
      the RT values 2 and 4 months post-stroke on the unaffected side did not differ
      from corresponding values in CTLs. Significantly higher RT values on the affected
      side when compared to the unaffected side were found both at 2 months (39%; p <
      0.05) and at 4 months (43%; p < 0.01). No significant difference existed on the
      affected side between the 2nd and 4th months. A high (r = 0.80) and significant
      (p < 0.0001) correlation coefficient was calculated between the changes in RT
      values recorded at 2 and 4 months. Low and not significant correlations were
      computed between these RT changes and factors such as the ROM (r = -0.24), the
      Ashworth score (r = 0.23) and the Fugl-Meyer lower extremity motor subscore (r = 
      0.26). Present results indicate that: (1) changes in the non-reflex component are
      already present 2 months after stroke but do not increase significantly between
      the 2nd and 4th months; (2) these changes are not related to the level of
      impairment; and (3) myometry testing at 2 months could be used as a preventive
      measure to detect patients more at risk of developing severe passive muscle
      stiffness.

PMID- 9271149
TI  - Prediction of recovery from upper extremity paralysis after stroke by measuring
      evoked potentials.
AB  - Paralysis of the upper extremity is a severe motor impairment that can occur
      after stroke. Prediction of recovery from paralysis is difficult and is primarily
      based on subjective clinical evaluation. However, the integrity of the
      sensorimotor system can be assessed objectively and quantitatively by measuring
      evoked potentials. In this retrospective exploratory study, we evaluated the
      predictive value of motor and somatosensory evoked potentials for recovery from
      paralysis of the upper extremity. Motor and somatosensory evoked potentials were
      recorded in 29 patients who had had their first-ever infarction in the territory
      of the middle cerebral artery and who exhibited paralysis of the upper extremity.
      At follow-up, seven patients showed motor recovery. The evoked potential data
      were dichotomized into present or absent and related to the occurrence of motor
      recovery. Analysis revealed a significant association between the presence of
      evoked potentials early after stroke and the observed occurrence of motor
      recovery. These results suggest strongly that evoked potentials predict the
      occurrence of motor recovery of upper extremity paralysis in patients suffering
      from first-ever infarction in the territory of the middle cerebral artery.

PMID- 9271150
TI  - Self-selected walking speed in patients with hemiparesis after stroke.
AB  - "Self-selected walking speed" was measured in 18 patients with hemiparesis after
      stroke and compared with that in a healthy control group. The average speed of
      the patient group for a 30 m walk was 0.78 m/s (SD 0.24) and of the control group
      1.69 m/s (SD 0.05). The intraindividual variation for the patients was 0.004 m/s
      and the interindividual variation 0.37 m/s. For the controls, the corresponding
      values were 0.000 m/s and 0.003 m/s, respectively. "Self-selected walking speed"
      correlated significantly with "functional walking test" (r = 0.91) and, "number
      of steps" (r=0.97) as well as with self-assessment scores of walking ability and
      stiffness, the degree of motor function of the lower extremities, muscle tone and
      balance. The significant correlation between "self-selected walking speed" and
      other studied tests strengthens their validity and implies that they can be used
      separately or in combination to evaluate the effect of rehabilitation programmes
      in patients with hemiparesis after stroke.

PMID- 9271151
TI  - Reduced mobility in the cervico-thoracic motion segment--a risk factor for
      musculoskeletal neck-shoulder pain: a two-year prospective follow-up study.
AB  - The aim of this study was to evaluate the variations in C7-T1 mobility in order
      to decide whether inverse C7-T1 function, defined as equal or less mobility in
      motion segment C7-T1 compared with T1-T2, could be used for prediction of neck
      shoulder pain (NSP). One hundred and sixty-one female laundry workers
      participated in a prospective two-year follow-up study which included a self
      report questionnaire and clinical examinations. The present study showed that the
      incidence of inverse C7-T1 function was 33% per year and subjects classified as
      having an inverse C7-T1 function three or more times during the follow-up period
      had an elevated risk of NSP (RR 3.1, CI 95% 1.1-6.9). According to the authors'
      interpretation, lack of synchronous mobility distribution between adjacent motion
      segments might be a provoking factor. Inverse C7-T1 function predicts NSP related
      to the cervico-thoracic articulations and yields a positive predictive value of
      84%. Assessments must be repeated, however.

PMID- 9271152
TI  - Force output and energy metabolism during neuromuscular electrical stimulation: a
      31P-NMR study.
AB  - The purpose of this study was to determine the acute physiologic effects of two
      electrical stimulation protocols commonly used for muscle rehabilitation. Surface
      electrodes were used to provide 12 stimulations of the calf musculature. In
      protocol A the duty cycle was fixed at 1:1 (10-second stimulation: 10-second
      rest); for protocol B it was 1:5 (10-second stimulation: 50-second rest). We
      continuously recorded isometric plantarflexor force in six healthy male subjects
      during stimulation using a load cell connected to a foot pedal ergometer.
      Metabolic changes in the stimulated gastrocnemius muscle were monitored in the
      supine position using 31P-NMR spectroscopy (Phillips 1.5 tesla NMR machine).
      Relative changes in phosphocreatine (PCr), inorganic phosphate (Pi), and
      intracellular pH (pHi) were obtained during stimulation and recovery, using a 1.5
      cm RF surface antenna. Over the 12 stimulations, protocol A produced a
      significantly (p < 0.001), greater force decline (protocol A: 30.4 +/- 1.3%,
      protocol B: 13 +/- 0.8%); a significantly (p < 0.005), greater increase in Pi/PCr
      (protocol A: 210%, protocol B: 50%); and a significantly (p <0.001), lower pHi
      (protocol A: 6.8 +/- 0.16, protocol B: 7.03 +/- 0.12). We conclude that the
      shorter duty cycle produces more fatigue throughout the stimulation period,
      possibly as a result of greater intracellular acidosis and reduced availability
      of the high energy phosphate PCr. The clinical application of this finding
      relates to the selection of a stimulation protocol that maximizes strength gains
      in atrophic vs healthy muscle.

PMID- 9271153
TI  - Effect of training on physical capacity and physical strain in persons with
      tetraplegia.
AB  - The effects of quad rugby training on physical capacity and physical strain
      during standardized activities of daily living were investigated in 9 trained (A)
      and 5 untrained quad rugby players (B), and 7 inactive persons with tetraplegia
      (C) at 0, 3 and 6 months after the start of a quad rugby training program
      (1.5h.wk[-1]). Physical capacity was measured as maximal isometric strength, peak
      power output (POpeak) and peak oxygen uptake (VO2peak) on a stationary wheelchair
      ergometer. Physical strain was expressed as a percentage of heart-rate reserve.
      No measurable training effects could be observed for POpeak, VO2peak and physical
      strain. A significant rise in maximal isometric strength was found in group B
      after 3 and 6 months of training, whereas no significant changes were found in
      groups A and C. The results suggest that a higher training frequency and/or
      intensity may be needed to gain significant training effects for POpeak and
      VO2peak.

PMID- 9271154
TI  - Isokinetic and psychophysical lifting strength, static back muscle endurance, and
      magnetic resonance imaging of the paraspinal muscles as predictors of low back
      pain in men.
AB  - Magnetic resonance imaging was used to determine the cross-sectional areas and
      the T2-weighted and proton density-weighted signal intensities of the paraspinal
      muscles in a group of 128 men, aged 35-63, who had varied histories of
      occupational and leisure-time physical activities. These measures, and the
      isokinetic lifting, psychophysical lifting, and static back muscle endurance
      tests were examined as predictors of low back pain over 12 months of follow-up,
      in the 43 men who reported no low back pain in the year preceding testing. None
      of the imaging measures or the muscle function tests was useful as a predictor of
      future low back pain. Associations with the frequency of low back pain before
      testing were investigated in the larger group. Smaller total cross-sectional area
      of the paraspinal muscles and greater signal intensities had weak but significant
      correlations with more frequent low back pain in the previous year, possibly due
      to muscle atrophy.

PMID- 9271155
TI  - Functional uncoupling between the receptor and G-protein as the result of PKC
      activation, observed in Aplysia neurons.
AB  - Application of either acetylcholine (ACh), dopamine (DA), histamine (HA), or Phe
      Met-Arg-Phe-NH2 (FMRFamide) induces a K+-current response in the identified
      neurons of Aplysia under voltage clamp. This type of response is mediated by a
      pertussis toxin (PTX)-sensitive G-protein, Gi or Go. Extracellular application of
      60 microM phorbol dibutyrate (PDBu), an activator of protein kinase C (PKC), to
      these cells markedly depressed all the K+-current responses to ACh, DA, HA, and
      FMRFamide. The depressing effect of PDBu lasted for at least 60 min despite
      continuous washing with the normal perfusing medium. Application of PKC
      inhibitors such as 100 microM H-7 or 10 microM staurosporine and PKCI(19-31)
      prior to the application of PDBu significantly decreased the depressing effects
      of PDBu. In contrast, an intracellular injection of okadaic acid (OA), an
      inhibitor of protein phosphatase 1 and 2A, significantly augmented the blocking
      effect of PDBu. Intracellular injection of the PKC catalytic subunit induced a
      similar depressing effect as observed with PDBu. The dose-response curves
      obtained with different transmitters all shifted downward after the activation of
      PKC, but the ED50 of each transmitter remained unchanged. Furthermore, the K+
      current responses induced by the intracellular application of GTPgammaS were not
      depressed at all, even after the receptor-induced K+-current responses of the
      same cell were markedly depressed. These results strongly suggest that PKC
      phosphorylated a certain coupling site between the receptor and G-protein, and
      impaired the signal transduction necessary for triggering the K+-channel opening.

PMID- 9271156
TI  - Contribution of mitochondria to the removal of intracellular Ca2+ induced by
      caffeine and rapid cooling at low temperatures in ferret ventricular muscles.
AB  - We investigated the role of mitochondria in the removal of intracellular Ca2+
      which was increased by caffeine (15 mM, Caf), rapid lowering of the solution
      temperature from 30 to 4 degrees C (rapid cooling, RC), and electrical
      stimulation (0.07 Hz, ES). For this purpose, the intracellular Ca2+ concentration
      ([Ca2+]i) was measured using aequorin from the superficial cells of ferret
      papillary muscles. The three maneuvers induced transient changes in [Ca2+]i with
      different time courses. The decay time of the aequorin light signal (DT) in the
      Caf-induced Ca2+ release was significantly prolonged by the inhibitors for Na+
      Ca2+ exchanger (Ni2+, Na+-free solution) at higher temperatures (> or = 12
      degrees C). In the caffeine application at lower temperatures (< or = 12 degrees
      C), the inhibitors for mitochondria (ruthenium red, NaN3) significantly prolonged
      the DT but other inhibitors were ineffective. In the RC-induced Ca2+ release, DT
      was significantly prolonged by the mitochondrial inhibitors but other inhibitors
      were not effective. In the ES-induced Ca2+ release, each inhibitor for the
      sarcoplasmic reticulum (SR) (thapsigargin and 2,5-di(tert-butyl)-1,4
      benzohydroquinone) prolonged the DT at all temperatures. The inhibitors for Na+
      Ca2+ exchanger slightly prolonged the DT only at higher temperatures, and the
      mitochondrial inhibitors did not alter the DT at any temperature. These results
      suggest that mitochondria substantially transport Ca2+ when the Ca2+ uptake by
      the SR and Na+-Ca2+ exchanger are inhibited and [Ca2+]i is increased with a
      slower time course.

PMID- 9271157
TI  - Ca2+ release induced by rapid cooling and caffeine in ferret ventricular muscles.
AB  - The Ca2+ release induced by rapid cooling (RC) and caffeine in ferret ventricular
      muscles was investigated. For this purpose, the author measured the intracellular
      Ca2+ concentration ([Ca2+]i) using aequorin. Rapid lowering of the temperature of
      the bathing solution from 30 degrees C to low temperatures after the cessation of
      electrical stimulation transiently increased [Ca2+]i. The peak of [Ca2+]i was
      altered depending upon the temperature in RC. [Ca2+]i reached 1.59 microM when
      the temperature was lowered from 30 to 4 degrees C. Caffeine (15 mM) applied
      during cooling after the decline of RC-induced intracellular Ca2+ signal caused
      an increase in [Ca2+]i. The author assumed that the total Ca2+ content in the SR
      was the sum of the peaks of [Ca2+]i increased by RC (Ca(RC)) and caffeine
      application (Ca(caf)). The fractional Ca2+ release induced by RC
      [Ca(RC)/"assumed" total released Ca2+ from the SR(%)] was 63.7% at 4 degrees C.
      The peak of Ca2+ increased by RC was proportional to the "assumed" total released
      Ca2+ from the SR. No significant correlation was observed between RC-induced
      [Ca2+]i change and the [Ca2+]i before RC. However, in Na+-deficient solutions
      (Li+ or TMA+ replacement), the fractional Ca2+ release induced by RC was
      decreased; this inhibition shows a dependence upon extracellular Na+
      concentration. In contrast, the fractional Ca2+ release by caffeine application
      after RC was enhanced. These results suggest that: 1) RC releases a fraction of
      the Ca2+ accumulated in the SR and 2) the mechanism of RC-induced Ca2+ release in
      mammalian cardiac muscle is different from that of RC-induced Ca2+ release in
      frog skeletal muscles, which requires an increase in [Ca2+]i before RC.
      Extracellular Na+ might modify RC-induced Ca2+ release through a change in
      [Na+]i.

PMID- 9271158
TI  - Effects of ruthenium red on the cellular functions and ultrastructure in intact
      ferret ventricular muscles.
AB  - The effects of ruthenium red (RR) on the cellular functions (intracellular Ca2+
      handling and contraction) and permeation of the dye through the cell membrane
      were investigated in intact ferret papillary muscles. The intracellular Ca2+
      concentration ([Ca2+]i), measured using aequorin, was simultaneously recorded
      with tension. The permeation of the dye through the cell membrane was studied
      with electronmicroscopy. The preparation was continuously stimulated at 0.2 Hz
      and treated with 50 microM RR at 30 degrees C. [Ca2+]i was increased by
      electrical stimulation (0.07 and 2 Hz) and rapid cooling (from 30 to 4 degrees C)
      (RC). In electrical stimulation, RR time-dependently decreased the peak light of
      aequorin without a significant change in the time course at 30 degrees C.
      However, in RC, treatment with RR for about 100 min significantly prolonged the
      decay time of the light signal and increased the peak light. The peak tension in
      RC was decreased after treatment with RR for a longer time. The pCa-tension
      relation of skinned preparations was significantly shifted to the right by 50
      microM RR. In the RR (50 microM)-treated specimens, mitochondrial outer membranes
      were darkly stained if OsO4 was used for fixation. Even though the specimen
      treated with 500 microM RR was fixed without OsO4 and electron staining, the
      matrices of mitochondria became electron dense. We concluded that RR could
      penetrate into intact mammalian cardiac myocytes, and that RR inhibits the
      release of Ca2+ from the sarcoplasmic reticulum in electrical stimulation,
      inhibits mitochondrial Ca2+ uptake, and decreases the Ca2+ sensitivity of the
      myofilaments.

PMID- 9271159
TI  - Hybrid logistic characterization of isometric twitch force-time curve of intact
      blood-perfused canine right ventricular papillary muscle.
AB  - We previously found that a ventricular isovolumic pressure-time curve could be
      well fitted by the difference between two S-shaped logistic curves for the
      pressure rising and falling components, and called it "hybrid logistic" function:
      P(t)=A/[1+exp[-(4B/A)(t-C)]]-D/[1+exp[-(4E/D)(t-F)]]+G. We reported that the
      parameters of this hybrid logistic function are useful to characterize left
      ventricular contraction and relaxation comprehensively. In this study, we
      investigated how well this hybrid logistic function could fit the isometric
      twitch force-time curves of cross-circulated right ventricular papillary muscles
      of 7 dogs. This function precisely fitted the isometric force curves with
      correlation coefficients above 0.9996, much better than another fitting function
      (F(t)=C(t/A)(B)exp[1-(t/A)(B)]) proposed by Nwasokwa. The present results
      indicate that our hybrid logistic function can also reasonably express the canine
      right ventricular papillary muscle isometric twitch force-time curve. We suggest
      the possibility that the parameters of this hybrid logistic function are also
      useful to comprehensively characterize right ventricular papillary muscle twitch
      contraction and relaxation.

PMID- 9271160
TI  - Cross-relaxation times of normal and biochemically induced osteoarthritic rabbit
      knee cartilages.
AB  - We measured the spin-lattice relaxation times (T1) of water protons and
      intermolecular cross-relaxation times (T(IS)) from irradiated protein protons (f2
      irradiation at 1.95 or -4.00 ppm) of rabbit normal and monoiodoacetate-induced
      degenerated knee articular cartilages to observed water protons. The mean values
      of T1 (T1) for control and degenerated rabbit knee cartilages were 1.87+/-0.15
      (mean+/-SD, n=29) and 1.82+/-0.13 s (n=34), respectively. The mean values of
      water content (W(H2O)) for control and degenerated rabbit knee cartilages were
      82.9+/-2.09 (n=26) and 83.1+/-2.57% (n=28), respectively. These values were not
      statistically different from each other. However, the mean values of T(IS)
      (T(IS)) for normal knee articular cartilage were significantly different from
      those for degenerated cartilage: (normal), T(IS) (f2=1.95 ppm)=2.46+/-0.62 s
      (n=28), T(IS) (f2=-4.00 ppm)=4.25+/-1.26 s (n=26); (degenerated), T(IS) (f2=1.95
      ppm)=1.99+/-0.76s (n=34), T(IS) (f2=-4.00 ppm)=3.33+/-0.76 s (n=31). Obtained
      results may be attributed to the reported switchover from type II to type I
      collagen syntheses in osteoarthritic cartilage, resulting in broad collagen
      fibers. This specificity of cross-relaxation effect may prove useful in the
      noninvasive and pathophysiological evaluation of cartilage tissues in vivo.

PMID- 9271163
TI  - A method to estimate the transient interstitial osmolarity change upon
      application of osmotic stress in perfused rat submandibular gland.
AB  - Transient osmolarity changes in the interstitium of perfused rat submandibular
      glands were estimated by measurement of the interstitial Cl- concentration ([Cl
      ]ECF) with an Ag-AgCl electrode upon application of osmotic stress by the
      addition or subtraction of NaCl. A simple model was used to describe the
      interstitial osmolarity changes upon the application of osmotic stress. The
      measured [Cl-]ECF values and interstitial osmolarities were fit well by an
      exponential function derived from the model. The good fit of the theoretical
      curve indicates that this model describes adequately the changes in interstitial
      osmolarity after switching the perfusate osmolarity to a new value.

PMID- 9271161
TI  - Suppressing Na+ influx induces an increase in intracellular ATP concentration in
      mouse pancreatic beta-cells.
AB  - The effects of suppressing Na+ influx on the activity of ATP-sensitive K+
      channels (K(ATP) channel) and intracellular ATP concentration in mouse pancreatic
      beta-cells were studied. Lowering extracellular Na+ concentration brought about a
      closing of K(ATP) channels. The activity of K(ATP) channels was markedly
      inhibited by the addition of amiloride, a blocker of Na+/H+-counter transporter.
      Mannoheptulose completely eliminated the inhibition otherwise induced by
      amiloride. Monensin, an electroneutral Na+/H+ antiporter, remarkably increased
      the activity of K(ATP) channels. Removing extracellular Ca2+ also caused
      inhibition of the channel activity. ATP measurement experiments using isolated
      islets revealed that the intracellular ATP concentration of islet cells was
      significantly increased by incubating either with amiloride or a low Na+
      solution. The measurement of fluorescence excited at 360 nm demonstrated that
      both suppressing Na+ influx and inhibition of Na+/K+-pumps caused a transient
      increase in the reduced form of pyridine nucleotide. These findings indicate that
      a decrease in Na+ influx could cause an elevation in intracellular ATP
      concentration probably through inducing a fall in ATP consumption at the Na+/K+
      pump sites.

PMID- 9271162
TI  - Induction of apoptosis in human leukemic cells by magnetic fields.
AB  - When human myelogenous leukemic cell lines, HL-60 and ML-1, were exposed to 50 Hz
      electromagnetic fields (EMFs), nucleosome-sized DNA fragmentation (a biochemical
      marker of apoptosis) was induced as assessed by agarose gel electrophoresis.
      However, EMFs could not induce detectable DNA fragmentation in either human
      peripheral blood leukocytes or polymorphonuclear cells. The minimum exposure
      period required for the onset of DNA fragmentation in leukemic cells was 1.0 h.
      Although adverse effects of EMFs on human health have been reported, the
      apoptosis-inducing action of EMFs on leukemic cells may suggest a possible
      medical application.

PMID- 9271164
TI  - R-form lipopolysaccharides (LPS) of Gram-negative bacteria as possible vaccine
      antigens.
AB  - The antigenic and immunogenic properties of R-form lipopolysaccharides (LPS) of
      Pseudomonas aeruginosa, Salmonella spp., Escherichia coli and Shigella spp. were
      studied. The results showed the presence of antigenic relationships among P.
      aeruginosa R mutants with different structures of the LPS core lipid A region and
      also among E. coli, Shigella and P. aeruginosa R-LPS, but not with S. minnesota
      Re-LPS. Vaccines prepared with R-LPS proved to be effective preparations for the
      active immunization of mice against P. aeruginosa infection. The vaccine
      stimulated 40-100% protection in mice depending upon the scheme of immunization.

PMID- 9271165
TI  - Expression and quantification of the iC3b-binding protein in different Candida
      albicans strains and their morphological stages.
AB  - Expression and quantification of the iC3b-binding protein in yeast, germ-tube,
      and mycelial forms of several Candida albicans strains were studied. Ten isolates
      were obtained from patients with recurrent vaginal candidosis. The germ-tubes
      generated at 37 degrees C and the mycelial forms of all strains grown at 30
      degrees C, as well as most of the mycelial forms grown at 37 degrees C, were able
      to bind complement-coated sheep erythrocytes (EAiC3b). ELISA results revealed
      that a decrease in the binding of EAiC3b by the mycelial form of strains CBS 5982
      and K10 correlated with a decrease of the expression of the iC3b-binding protein,
      detected by cross-reaction with the monoclonal antibody OKM1, recognising the
      alpha chain of human CR3. Expression of the iC3b-binding protein in other
      strains, binding EAiC3b, was higher in the mycelial form or very similar to that
      of germ-tubes. The dependence of the expression of the iC3b-binding protein on
      the morphological stages of individual C. albicans isolates suggests a possible
      association with the virulence of these strains.

PMID- 9271166
TI  - Reduced intestinal colonisation with F18-positive enterotoxigenic Escherichia
      coli in weaned pigs fed chicken egg antibody against the fimbriae.
AB  - Newly weaned pigs were fed a basal diet containing either egg antibody against
      fimbriae F18 at a high or low level, control egg powder or no egg, and challenged
      with enterotoxigenic Escherichia coli with fimbriae F18. The challenge was
      repeated after termination of the antibody treatment. Antibody-containing egg
      powder was produced by vaccination of hens with semi-purified fimbriae of the two
      variants F18ab and F18ac. Pigs eating egg powder with antibody against the same
      fimbrial variant were fully protected, even if the vaccine for the hens was
      produced with a different serotype devoid of enterotoxins. The effect was dose
      dependent. The high dose of antibody against the heterologous variant of fimbriae
      F18 reduced colonisation at a level which was not significant. Ingestion of egg
      antibody partially suppressed the build-up of anti-colonisation immunity. Oral
      application of egg antibodies offers a promising approach for the prevention of
      infectious diseases of the digestive tract.

PMID- 9271167
TI  - Human IgG binding ability of streptococcal M3 protein: its related complement
      activation-dependent M3 protein polymerization.
AB  - We previously showed that M3 protein bound both fibrinogen and human serum
      albumin. Here, I report that M3 protein also has affinity for human
      immunoglobulin G. In contrast, M3 protein did not show affinity for polyclonal
      immunoglobulin G from other mammalian species (rabbit and goat). On the human
      immunoglobulin G molecule, the Fab domain was mainly responsible for the
      interaction with M3 protein, although the Fc region had a low degree of
      interaction with the M3 protein. Also, since the 35 kDa C-terminal fragment of M3
      protein bound human immunoglobulin G, the binding site for human immunoglobulin G
      on M3 protein is present in this portion of the protein. The M3 protein-human
      immunoglobulin G complexes initiated complement activation via both classical and
      alternative pathways in normal human serum. When C3 was precipitated in the fluid
      phase with anti-C3 antibody and analyzed by SDS-PAGE under reducing conditions,
      M3 protein coprecipitated with the complexes and was polymerized. However, there
      was no polymerization of M3 protein when incubated with normal human serum
      treated with magnesium-ethyleneglycol-bis-(beta-aminoethyl ether)-N,N,N',N'
      tetraacetic acid in the presence of M3 protein. Thus, this polymerization is
      mostly mediated via the classical activation pathway. It is probably helpful for
      the understanding of the antiphagocytic activity of M protein.

PMID- 9271169
TI  - Salmonella enterica var Typhimurium and Salmonella enterica var Enteritidis
      express type 1 fimbriae in the rat in vivo.
AB  - In a series of experiments rats were dosed with purified type 1 fimbriae from
      Salmonella enterica var Enteritidis or with fimbriated cultures of either S.
      enterica var Typhimurium or S. enterica var Enteritidis. Paraffin-wax embedded
      histological sections of jejunal and ileal tissue were taken and stained by the
      streptavidin biotin complex (sABC) staining technique for the detection of
      salmonella and type 1 fimbriae. On oral infection with Enteritidis and
      Typhimurium both bacteria were shown to be closely associated with the rat ileal
      epithelium and expressed type 1 fimbriae, thus clearly demonstrating that type 1
      fimbriae are expressed by salmonellae in vivo. Moreover, association with the
      ileum was also shown to occur when purified type 1 fimbriae were orally
      administered to rats. Our results suggest that type 1 fimbriae alone or in
      combination with other fimbriae may play an important role in the early stages of
      infection with these pathogenic bacteria.

PMID- 9271168
TI  - LasA, alkaline protease and elastase in clinical strains of Pseudomonas
      aeruginosa: quantification by immunochemical methods.
AB  - Thirty Pseudomonas aeruginosa strains were isolated from the sputa of cystic
      fibrosis patients. In each culture supernatant, the amount of three exoproteases
      (LasA, alkaline protease and elastase) was determined using immunochemical
      procedures. These assays used selected peptide-MAP (multiple antigen peptide)
      strategy as antigen for animal immunisation. The method appeared to be
      reproducible, simple, sensitive and specific without cross-reactivity between the
      antisera. The resulting values differed from one strain to another mostly for
      elastase production. Despite the fact that four genes (lasA, lasB, lasR and rhlR)
      were shown to be necessary for full elastolytic activity, it was obvious that if
      LasA was not secreted in a naturally non-elastase-producing strain, in return in
      an elastase-producing strain, there were no apparent relationships between LasA
      and elastase production and between LasA and alkaline protease secretion.
      Furthermore, in vitro, the secretion of the three exoproteases seemed to be
      independent of the mucoid or non-mucoid phenotype of the bacteria.

PMID- 9271170
TI  - Comparative study of DNA-based immunization vectors: effect of secretion signals
      on the antibody responses in mice.
AB  - The presence of a signal sequence preceding the gene encoding a target antigen in
      a DNA vaccine should facilitate secretion of the in vivo translated antigen. The
      immune responses elicited upon injection with such a vector could differ from
      those induced by the same vector lacking a signal sequence. In the present study,
      the humoral responses elicited in mice immunized with two plasmids, either
      containing or lacking the human tissue plasminogen activator signal sequence,
      were compared. Both plasmids encode the chimeric antigen ZZN4, containing a
      malaria antigen Pf332-derived sequence (N4) linked to a bacterial fusion partner
      (ZZ). In vitro transfection of COS cells with each plasmid and treatment of the
      transfectants with brefeldin A confirmed that secretion of ZZN4 via the
      endoplasmic reticulum and Golgi pathway only occurred in cells transfected with
      the signal peptide-encoding plasmid. Repeated intramuscular injections of mice
      with either of the plasmids elicited comparable antibody responses to ZZN4 with
      regard to kinetics, specific IgG levels and persistence. These results indicate
      that in vivo transfection of muscle cells by either of these two plasmids
      generated comparable levels of antigen available for B-cell recognition and for
      uptake by antigen-presenting cells, despite the differential intracellular
      targeting of the encoded antigen. The relevance of these findings for the design
      of DNA vaccine vectors is discussed.

PMID- 9271172
TI  - A 200 kDa protein is associated with haemagglutinating isolates of Moraxella
      (Branhamella) catarrhalis.
AB  - Moraxella catarrhalis adheres to human erythrocytes by means of a proteinaceous,
      trypsin sensitive, heat modifiable haemagglutinin. A 200 kDa protein was found to
      be associated with haemagglutinating isolates of M. catarrhalis. This protein was
      present on all haemagglutinating isolates (n = 17), but was absent on the non
      haemagglutinating isolates (n = 23) examined. This protein demonstrated heat
      modifiable properties in sodium dodecyl sulfate and was degraded by trypsin.
      Immunoblot assays with polyclonal antiserum indicated that the 200 kDa protein
      was associated exclusively with haemagglutinating isolates and antibodies to this
      protein did not recognise epitopes on non-haemagglutinating isolates. This
      protein, which appears to be a surface expressed protein may be a haemagglutinin
      of M. catarrhalis.

PMID- 9271171
TI  - Circulating profile of Th1 and Th2 cytokines in tuberculosis patients with
      different degrees of pulmonary involvement.
AB  - To investigate whether differences in the degree of pulmonary tuberculosis
      lesions could be accompanied by changes in the pattern of circulating cytokines,
      29 untreated tuberculosis patients showing mild (n = 10), moderate (n = 5) or
      advanced (n = 14) pulmonary disease, and 12 age-matched healthy controls (mean +/
      S.D., 36 +/- 15 years) were studied. ELISA methods for the evaluation of
      interferon-gamma, interleukin-2, interleukin-4, and interleukin-10 indicated that
      all patients had increased serum levels of the four cytokines in relation to
      controls. Mean titers of interferon-gamma and interleukin-2 in mild and moderate
      patients appeared higher than in those with advanced disease, whereas moderate
      and advanced patients showed the higher levels of IL-4 in comparison to mild
      cases. Raised levels of interleukin-10 were more prevalent in advanced disease,
      and statistically different from those in mild patients. This cytokine pattern
      may help to explain findings wherein mild tuberculosis is characterized by
      preserved cellular immune responses while advanced disease is accompanied by an
      impairment of such parameters.

PMID- 9271173
TI  - Ischemic cardiomyopathy--revascularization vs. transplantation.
AB  - Advanced coronary artery disease (CAD) and ischemic cardiomyopathy with elevated
      pulmonary artery pressures are criteria of a severe illness. In selected cases
      surgical revascularization has proved beneficial in terms of survival, reduction
      of morbidity and lowering the frequency of angina pectoris [6] in numerous
      studies over the past 25 years. But most of the earlier publications concentrated
      on patients with angina pectoris (AP) as a dominant symptom. Patients without AP
      but with predominant signs of congestive heart failure were largely excluded.
      This has changed recently [1-3,7,8,10,12,16,18] with the advent of the concept of
      hibernating myocardium. This term is defined as the presence of persistent
      myocardial and left ventricular dysfunction at rest due to reduced regional
      coronary blood flow that can be partially or completely restored to normal by
      myocardial revascularization [5,19]. Salvage of viable myocardium by successful
      revascularization improves left ventricular dysfunction. Diagnosis of hibernating
      myocardium is crucial because it does not leave the patient with chronic heart
      failure a candidate only for cardiac transplantation. Instead, these patients'
      left ventricular dysfunction is potentially reversible following
      revascularization by coronary bypass surgery. Furthermore we face a critical
      shortage of donor organs and extending waiting lists for possible transplant
      candidates. Following the start of the heart transplantation (HTX) program at our
      institution more than 690 operations were performed until September 1995. We
      screened more than 1600 patients for their eligibility as cardiac transplant
      recipients or for other forms of treatment. In this group of patients it has
      always been our policy to revascularize rather than transplant whenever possible.

PMID- 9271174
TI  - International experience with the CardioWest total artificial heart as a bridge
      to heart transplantation.
AB  - As the number of potential heart donors remains constant and the number of
      potential recipients continuous to increase, the need for circulatory devices to
      bridge patients becomes more important. The CardioWest total artificial heart
      (TAH) is a pneumatic, implantable system that totally replaces the failing
      ventricles. It has been utilized worldwide as a bridge to heart transplantation
      in 79 patients. There were 73 males and six females who received the TAH.
      Currently three patients remain on the device waiting for transplantation. A
      total of 55 patients (70%) were transplanted of which 50 survived (91% of
      patients transplanted) and were discharged home. Idiopathic/dilated
      cardiomyopathy was the most common etiology followed by ischemic cardiomyopathy.
      The mean duration of implant was 34 days (range 0-186 days) and the mean age of
      the group was 45 years (range 16-62 years). Twenty-one patients died while on the
      device. Multiple organ failure was the major cause of death. There were a total
      of 255 complications in this group that included reoperation, bleeding, hepatic
      failure, renal failure, respiratory failure, neurologic events, thromboembolic
      events, infections, device malfunction, and fit complications. This represented a
      mean complication rate of three events per patient. The survival rate for the
      CardioWest TAH of 91% of the patients who reached transplantation is an
      improvement over that of the Symbion registry (55% of those transplanted)
      probably as a result of a better patient selection and better control of the
      coagulation system. These results are also comparable to those survival results
      obtained with other biventricular and left ventricular assist devices currently
      available.

PMID- 9271175
TI  - Will permanent LVADs be better than heart transplantation?
AB  - Current interest in permanent mechanical support systems has been renewed as a
      result of the present shortage of human heart donors, and in view of the
      satisfactory results obtained with their use as a bridge-to-transplant. As the
      number of donors is unlikely to increase dramatically in the near future, there
      is an urgent need to develop mechanical alternatives to transplantation.
      Preliminary data on the use of the implantable electric LVAD as a bridge-to
      transplant indicate that the adverse clinical and mechanical events in
      outpatients are few and do not preclude use of the device on a permanent basis.
      Except for infections, transplant issues relating to need for endomyocardial
      biopsies, rejection, malignancies, and graft arteriosclerosis do not apply to
      LVAD recipients who face important issues relating to device durability, cost,
      and potential need for concomitant right heart support. This lack of data on long
      term durability contrasts with a yearly mortality rate of about 5% after the
      first year of transplant. With the initiation of clinical trials on the permanent
      use of the electric LVAD, several design modifications and upgrading of the
      currently available devices are expected. Completely sealed systems with steadily
      improving durability will hopefully appear. Inductive coupling techniques under
      investigation and development appear to be able to transmit energy without damage
      across the skin. It is anticipated that with more reliable electronic
      microprocessors, the future generation of implantable LVADs will be smaller, more
      reliable and longer lasting.

PMID- 9271176
TI  - Long-term mechanical circulatory support as a bridge to transplantation, for
      recovery from cardiomyopathy, and for permanent replacement.
AB  - Since 1988, 295 patients have undergone MCS at the German Heart Institute Berlin;
      246 received biventricular support with the extracorporeal pneumatically-driven
      Berlin Heart Assist Device, 49 received left ventricular support with implantable
      assist devices (33 Novacor, 16 TCI). Longer waiting periods for heart
      transplantation has caused the mean duration of MCS to increase from 12 days in
      1988 to 76 days in 1994. Of the 24 patients who underwent MCS for more than 90
      days, nine were implanted with a biventricular device, 12 with a Novacor device,
      and 15 with a TCI device. Eight patients with uni-ventricular devices remain on
      support after 200 days (range 203-600 days). Six of the Novacor patients could be
      discharged to a nursing home or to their own residences. One patient still on NC
      support after more than 600 days currently resides at his home and has regained
      normal physical activity. Minor pocket infections occurred in two TCI and four
      Novacor patients; one patient died of sepsis. A total of four patients could be
      weaned from LVAD after 160-347 days of MCS. An initial high level of beta1
      receptor antibodies disappeared completely during left ventricular support. This
      decline in auto-antibodies was paralleled by a dramatic improvement in cardiac
      function. LVEF remained unchanged up to 6 months after explantation. Long-term
      mechanical support has become a reality. Heart transplantation after prolonged
      MCS yields results comparable to primary HTx. Some patients exhibit immunological
      changes and a dramatic improvement in ventricular function under long-term MCS
      and can be weaned with extremely satisfying results.

PMID- 9271178
TI  - The development, evolution, and clinical utilization of artificial heart
      technology.
AB  - The ventricular assist device has evolved into an effective clinical tool to
      treat patients with severe heart failure. Left ventricular assist systems, such
      as the HeartMate, have demonstrated their utility as short- and long-term bridges
      to heart transplantation and their ability to effect a degree of ventricular
      recovery in some patients. These devices will soon be used more commonly as an
      alternative to transplantation.

PMID- 9271177
TI  - Mechanical circulatory support towards the permanent implantation.
AB  - Experience on wearable LVAS Novacor support accumulated since the first
      implantation in March 1993, includes in November 1995, seven cases (six male, one
      female, mean age 34) of cardiogenic shock, unresponsive to optimal medical
      management referred for urgent transplantation. Post-implantation period was free
      of any major incident in all but one, allowing transplantation in five, on an
      elective basis, and prolongation of the waiting period, at home in two. This
      experience suggests that a major breakthrough in the technology of mechanical
      support has been achieved: patients awaiting transplantation can be discharged
      home, which is both the result and an contributing factor of a satisfactory
      quality of life. This improvement allows speculations on coming studies on
      permanent implantation of the wearable LVAS Novacor, as an alternative therapy to
      cardiac transplantation.

PMID- 9271179
TI  - Development of a non-pulsatile permanent rotary blood pump.
AB  - For many years, a common belief was that non-pulsatile perfusion produced
      physiological and circulatory abnormalities. Since 1977 our group has reported,
      if a 20% higher blood flow was used more than required for a pulsatile blood
      pump, there would be no circulatory or physiological abnormalities. These
      experimental findings confirmed that there was no difference in clinical outcome
      when using a pulsatile or non-pulsatile blood pump. Furthermore, the non
      pulsatile rotary blood pump has demonstrated efficient and reliable performance
      in various clinical situations. The non-pulsatile blood pump is a simple and
      reliable design, that can be easily manufactured, and has the following desirable
      features. There is no need to incorporate heart valves, a large orifice inflow
      conduit, or a compliance volume-shifting chamber. Since an electrical motor
      operates continuously, the on-and-off motion required for a pulsatile pump is not
      necessary; therefore, it becomes a more efficient and durable system. Further,
      the control algorism is simpler and more reliable than a pulsatile pump.
      Considering these factors, the non-pulsatile blood pump can be selected for a
      permanently implantable assist device. To develop an implantable non-pulsatile
      cardiac device, it is necessary to incorporate seven features in the system such
      as: small size, atraumatic features, anti-thrombogenic features, anti-infection
      features, durable and simple design, and low energy requirement with easy
      controllability.

PMID- 9271180
TI  - The heartmate left ventricular assist system: worldwide clinical results.
AB  - To date 482 patients have been treated with TCI's HeartMate left ventricular
      assist system (LVAS) at 70 clinical centers worldwide. Of those, 433 patients
      have undergone treatment with the HeartMate IP (implantable pneumatic) LVAS,
      while 49 patients were treated with the HeartMate VE (vented electric) LVAS.
      Currently 65 patients are on the HeartMate LVAS: 51 on the pneumatic version and
      14 on the electric version. Of the 482 patients, 64% were transplanted after
      being supported for an average duration of 72 days (range 1-503 days) to arrive
      at a cumulative experience of greater than 100 patient years. Neural incidents
      occurred in 19% of the patients as a result of a variety of complications,
      including but not limited to air emboli, seizures, drug reactions, as well as
      thromboembolic complications whether device-related or not. Device-related
      complications remain quite low at the 2-3% range with minimal or no anticoagulant
      therapy. Fourteen patients on the electric version have been discharged to live
      at home for periods ranging from 1 to 7 months. Patients while being supported
      have successfully gone back to work or to school.

PMID- 9271181
TI  - Staged discharge out of hospital of the Novacor left ventricular assist system
      (LVAS) recipients.
AB  - The mobility afforded by the wearable Novacor LVAS provides the possibility for
      the recipients to leave the hospital, with undoubted improvements in their
      quality of life. A staged program for discharging LVAS recipients from the
      hospital has been set up at the Policlinico San Matteo of Pavia together with the
      Rehabilitation Center of Montescano and Baxter Novacor Service support, in order
      to proceed smoothly towards patient's self sufficiency and to minimize any
      associated risk. The steps are: stay in the hospital ward, discharge to
      Rehabilitation Center and discharge to home. Several excursions with and without
      an LVAS team member are encouraged before final discharge to home. Simple
      criteria of eligibility must be fulfilled to move to the next step. Every move
      towards a reduced presence of specialized personnel includes an appropriate
      training of the patient and relatives and a technical checkout of the needed
      equipment. During the stay at the Rehabilitation Center primarily the physical
      training and psychological preparation are taken care of by means of tailored
      programs. When the patient is discharged to home, the check of patient condition
      is performed weekly at the Rehab Center, bloodwork and technical evaluation is
      assessed once every two weeks and technical inspections at home twice per year.
      Complications are reported as in hospital protocol. Control parameters of the
      LVAS are reported only in case of alarms or abnormal operation. Periodic review
      of patient training is performed during the check visits, mostly focused on how
      to address emergency situations. The hospital is responsible for providing one
      LVAS operator available on call (all hours). Up to date, 11 patients received an
      implant of LVAS, 9 of them with the wearable system. All of these 9 patients made
      excursions out of the hospital and 4 patients have successfully undergone the
      staged program, showing a satisfactory general condition and restoration to
      social life.

PMID- 9271182
TI  - Out-of-hospital experience in patients with implantable mechanical circulatory
      support: present and future trends.
AB  - From March 1993 to August 1995, 33 patients received implantable VAD systems at
      our center. Nineteen patients received the wearable Novacor LVAS and 14 patients
      the TCI HeartMate device. Both systems enable the patients to be mobilized very
      quickly and some of them even do not require critical care after a few days. In
      our series 17 patients (eight Novacor, nine TCI) could be transferred to the
      normal floor. The wearable electrically driven Novacor system opens the
      opportunity of sending patients out of hospital. Since July 1994 we have referred
      five patients to a rehabilitation center, and six patients were sent home, three
      of them for more than 70 days. A number of factors are necessary to prepare the
      patient for being discharged. One of the most important things is to guarantee
      ambulatory patient care and to find an easy way for effective home monitoring.
      Our experience has shown that discharging these patients means giving them a
      maximum in quality of life and decreasing the costs by more than 50% in
      comparison to a stay in hospital for the whole time. Our results are encouraging
      to improve this strategy in the future.

PMID- 9271183
TI  - SIV/DeltaB670 transmission across oral, colonic, and vaginal mucosae in the
      macaque.
AB  - The primary mode of human immunodeficiency virus (HIV) transmission worldwide is
      by exposure to the virus at vaginal, rectal, and oral mucosal surfaces. To
      understand HIV/simian immunodeficiency virus (SIV) transmission events at mucosal
      portals of entry, we used the SIV-macaque model to determine if mucosal surfaces
      function as barriers and select for particular viral genotypes. Rhesus macaques
      were inoculated intravaginally, intracolonically, intrarectally, or orally with
      the complex primary viral isolate SIV/DeltaB670. Peripheral blood mononuclear
      cells, collected within the first two weeks postinoculation, were cloned and
      sequenced from all infected macaques. In the majority of the animals analyzed,
      multiple genotypes were identified, independent of the route of infection. These
      findings suggest that the mucosal barrier may play a minor role in the genotypic
      selection observed during sexual transmission of HIV and emphasize the need to
      evaluate the viral diversity present within the mucosal secretions of chronically
      infected individuals.

PMID- 9271185
TI  - Chemoattractant factors (IP-10, MIP-1alpha, IL-16) mRNA expression in mononuclear
      cells from different tissues during acute SIVmac251 infection of macaques.
AB  - We have used semiquantitative RT-PCR to monitor the expression of mRNA encoding
      chemoattractant factors IP-10, MIP-1alpha, and IL-16 in freshly isolated
      peripheral blood mononuclear cells (PBMCs), lymph node mononuclear cells (LNMCs),
      and mononuclear cells obtained after bronchoalveolar lavages (BALMCs) of two
      cynomolgus macaques inoculated intravenously with a pathogenic isolate of simian
      immunodeficiency virus, SIVmac251. Concomitant with the peak of systemic viral
      replication (two weeks after experimental inoculation) and proinflammatory
      cytokine IL-6 mRNA expression, high levels of MIP-1alpha and IP-10 mRNA were
      produced in LNMCs and BALMCs. In BALMCs, in which we have reported a marked
      progressive overexpression of IFN-gamma mRNA coinciding with an increase in the
      CD8+ lymphocyte percentages, we noticed a progressive overexpression of IL-16
      mRNA. Our results suggest the role of chemokines IP-10, MIP-1alpha, and IL-16 in
      the development of inflammatory and immune responses during the early stages of
      lentiviral infection.

PMID- 9271184
TI  - Immune and hematopoietic parameters in HIV-1-infected chimpanzees during clinical
      progression toward AIDS.
AB  - Until recently, chimpanzees were considered susceptible to human immunodeficiency
      virus type 1 (HIV-1) infection, but refractory to disease induction based on the
      asymptomatic status of all experimentally infected chimpanzees after over 10
      years postinfection (PI). However, a decline in peripheral CD4+ T cells was noted
      in one chimpanzee (C499) of the Yerkes cohort of HIV-1 infected apes, after 11
      years PI concurrent with increasing plasma viral load. These clinical signs were
      followed by the occurrence of opportunistic infections, thrombocytopenia, and
      progressive anemia leading to euthanasia. A second chimpanzee (C455) was
      transfused with blood from C499 collected during the symptomatic stage. Shortly
      thereafter, this second animal showed a rapid decline in peripheral CD4+ T-cell
      levels and sustained high viral load. Hematological analyses showed a 50%
      decrease in CFU-GM for both apes during the symptomatic phase and a reduction of
      40% and 73% of the total CFU despite normal levels of CD34+ cells in the bone
      marrow. Cryopreserved sequential PBMC samples from these two chimpanzees were
      analyzed for constitutive and PHA-P induced levels of cytokines and chemokines.
      Data show that whereas there were no detectable constitutive levels of mRNA
      coding for IL-2, 4, and 10, there appears to be a transient increase in IFN-gamma
      message level coincident with increased viremia and this IFN-gamma synthesis
      decreased with disease progression. PHA-induced cytokine mRNA analysis showed low
      or undetectable levels of IL-4 and IL-10 mRNA in all samples and a marked
      decrease in the levels of IL-2 shortly after HIV infection. In addition, there
      was also a gradual decrease in IFN-gamma mRNA with progression of disease. Of
      interest were the findings of high to normal levels of PHA-induced synthesis of
      the chemokines MIP-1alpha, MIP-1beta, and RANTES in samples during the
      asymptomatic and early symptomatic period, which also dramatically decreased at
      late stages of the disease. These data suggest important roles for IL-2, IFN
      gamma, and the chemokines in the regulation of immune responses in HIV-1-infected
      chimpanzees.

PMID- 9271186
TI  - Safety and immunogenicity of intramuscular and intravaginal delivery of HIV-1 DNA
      constructs to infant chimpanzees.
AB  - Any global strategy for controlling the human immunodeficiency virus (HIV)
      epidemic is likely to rely heavily on immunization of infants and children. Given
      the well-documented differences in children's responses to traditional vaccines,
      we initiated this study to extend our findings on DNA vaccination of adult
      chimpanzees to immunologically immature infant chimpanzees. Our findings were
      consistent with our previous work in adults as we observed that the DNA vaccines
      used here were both well tolerated and immunogenic within weeks of the initial
      vaccination.

PMID- 9271187
TI  - Mechanisms of protection induced by attenuated simian immunodeficiency virus. IV.
      Protection against challenge with virus grown in autologous simian cells.
AB  - Attenuated simian immunodeficiency virus (SIV) induces potent protection against
      infection with wild-type virus, but the mechanism of this immunity remains
      obscure. Allogeneic antibodies, which arise within animals as a result of SIV
      infection, might protect against challenge with exogenous SIV grown in allogeneic
      cells. To test this hypothesis, eight macaques were infected with attenuated SIV
      and subsequently challenged with wild-type SIV grown in autologous cells or
      heterologous cells. The results clearly demonstrated that animals infected with
      attenuated SIV are protected against wild-type SIV grown in autologous or
      heterologous cells. Thus, the hypothesis that live attenuated SIV protects by the
      induction of allogeneic antibodies is not tenable.

PMID- 9271188
TI  - Immunization of Macaca mulatta with aroA attenuated Salmonella typhimurium
      expressing the SIVp27 antigen.
AB  - Attenuated bacteria expressing foreign antigens stimulate both systemic and
      mucosal immune responses to the recombinant protein. We studied the infection of
      rhesus macaques with an attenuated Salmonella typhimurium expressing the simian
      immunodeficiency virus p27 capsid protein. Juvenile rhesus macaques were
      inoculated by intragastric intubation with doses ranging from 3 to 9 x 10(9)
      viable aroA attenuated S. typhimurium. The bacterial infection was self-limiting
      with no overt clinical signs. Salmonella were shed in the feces of macaques for
      approximately five days. Salmonella were isolated from fecal material to examine
      the in vivo stability of both the attenuating mutation and the integrated SIVp27
      expression cassette. All Salmonella isolates retained both the attenuating
      mutation and the recombinant expression construct. In vitro analysis showed that
      a minimum of 7.2 microg of p27 was delivered by a single oral dose with
      attenuated, recombinant S. typhimurium.

PMID- 9271189
TI  - A model for the maturation of protective antibody responses to SIV envelope
      proteins in experimentally immunized monkeys.
AB  - Studies using live attenuated virus vaccines in the simian immunodeficiency virus
      (SIV) rhesus macaque model have demonstrated broad protection against
      experimental challenge. Protection in these studies was found to be critically
      dependent on the length of time postvaccination, suggesting that protective
      immunity involves a necessary maturation of immune responses. The current study
      characterizes the evolution of protective envelope-specific antibody responses
      from monkeys inoculated with the highly attenuated SIV/17E-Cl virus vaccine. For
      comparison, the same antibody assays were used to characterize the properties of
      SIV envelope-specific antibodies elicited by inactivated whole virus and envelope
      subunit vaccines that failed to provide protection from experimental virus
      challenge. Results of these studies identify a continuous and complex maturation
      of envelope-specific antibody responses during the first six to eight months
      postinfection. Furthermore, the time required for maturation of SIV envelope
      specific antibodies parallels the time required for the development of protective
      immunity against experimental challenge with heterologous strains of SIV. While
      no single immune correlate of protection has been identified, we suggest that a
      combination of antibody parameters may serve as prognostic indicators in the
      development of candidate AIDS vaccines.

PMID- 9271190
TI  - Expression of the gibbon ape leukemia virus receptor-1 in rhesus macaque tissues.
AB  - A cDNA fragment specific for the rhesus macaque gibbon ape leukemia virus (GaLV)
      receptor (Glvr-1) was isolated by polymerase chain reaction (PCR) amplification
      and oligonucleotide primers specific for human Glvr-1 and a cDNA library derived
      from rhesus macaque brain. Sequence analysis of the fragment revealed the
      polypeptide domain necessary for infection by GaLV. This fragment was utilized to
      elucidate expression levels of Glvr-1 RNA in rhesus macaque tissues. By Northern
      blot analysis, Glvr-1 RNA is most abundantly expressed in the thymus and bone
      marrow, with detectable levels also in the brain and testes of juvenile male
      macaques. In the developing 70-days gestation fetus, Glvr-1 expression was
      observed predominately in the liver and spleen. Although additional studies are
      required, these studies support the notion that cell types involved in
      hematopoiesis express Glvr-1.

PMID- 9271191
TI  - Preclinical AIDS vaccine development: formal survey of global HIV, SIV, and SHIV
      in vivo challenge studies in vaccinated nonhuman primates.

PMID- 9271192
TI  - Afferent projections to the rat nuclei raphe magnus, raphe pallidus and
      reticularis gigantocellularis pars alpha demonstrated by iontophoretic
      application of choleratoxin (subunit b).
AB  - The aim of the present study was to identify the specific afferent projections to
      the rostral and caudal nucleus raphe magnus, the gigantocellular reticular
      nucleus pars alpha and the rostral nucleus raphe pallidus. For this purpose,
      small iontophoretic injections of the sensitive retrograde tracer choleratoxin
      (subunit b) were made in each of these structures. In agreement with previous
      retrograde studies, after all injection sites, a substantial to large number of
      labeled neurons were observed in the dorsal hypothalamic area and dorsolateral
      and ventrolateral parts of the periaqueductal gray, and a small to moderate
      number were found in the lateral preoptic area, bed nucleus of the stria
      terminalis, paraventricular hypothalamic nucleus, central nucleus of the
      amygdala, lateral hypothalamic area, parafascicular area, parabrachial nuclei,
      subcoeruleus area and parvocellular reticular nucleus. In addition, depending on
      the nucleus injected, we observed a variable number of retrogradely labeled cells
      in other regions. After injections in the rostral nucleus raphe magnus, a large
      number of labeled cells were seen in the prelimbic, infralimbic, medial and
      lateral precentral cortices and the dorsal part of the periaqueductal gray. In
      contrast, after injections in the other nuclei, fewer cells were localized in
      these structures. Following raphe pallidus injections, a substantial to large
      number of labeled cells were observed in the medial preoptic area, median
      preoptic nucleus, ventromedial part of the periaqueductal gray, Kolliker-Fuse and
      lateral paragigantocellular reticular nuclei. Following injections in the other
      areas, a small to moderate number of cells appeared. After gigantocellular
      reticular pars alpha injections, a very large and substantial number of labeled
      neurons were found in the deep mesencephalic reticular formation and oral pontine
      reticular nucleus, respectively. After the other injections, fewer cells were
      seen. Following rostral raphe magnus or raphe pallidus injections, a substantial
      number of labeled cells were observed in the insular and perirhinal cortices.
      Following caudal raphe magnus or gigantocellular reticular pars alpha injections,
      fewer cells were found. After raphe magnus or gigantocellular reticular pars
      alpha injections, a moderate to substantial number of cells were localized in the
      fields of Forel, lateral habenular nucleus and ventral caudal pontine reticular
      nucleus. Following raphe pallidus injections, only a small number of cells were
      seen. Our data indicate that the rostral and caudal parts of the nucleus raphe
      magnus, the gigantocellular reticular nucleus pars alpha and the nucleus raphe
      pallidus receive afferents of comparable strength from a large number of
      structures. In addition, a number of other afferents give rise to stronger inputs
      to one or two of the four nuclei studied. Such differential inputs might be
      directed to populations of neurons with different physiological roles previously
      recorded specifically in these nuclei.

PMID- 9271194
TI  - Colocalization of parvalbumin, calretinin and calbindin D-28k in human cortical
      and subcortical visual structures.
AB  - Several studies have demonstrated that three calcium-binding proteins parvalbumin
      (PV), calbindin D-28k (CB) and calretinin (CR) mark distinct subsets of cortical
      interneurons. This study demonstrates, in cortical and subcortical visual
      structures, the coexistence of two calcium-binding proteins in some neuronal
      subpopulations. The human visual cortex (VC), lateral geniculate nucleus (LGN).
      lateral inferior pulvinar (LIP) and superior colliculus (SC) were examined by a
      double-labelling immunocytochemical technique. The VC showed mostly separate
      populations of PV, CB and CR immunoreactive (-ir) interneurons, but also small
      populations of double-stained PV + CR and CR + CB neurons, while PV + CB neurons
      were less frequent. An average of 2.5% of the immunoreactive neurons were double
      stained for PV + CR and 7.1% for CR + CB in area 17, while this percentage was
      slightly higher in association area 18 (3.3 and 7.4%, respectively). In the LGN
      and LIP, double-stained neurons were scarce, but in the fibre capsule of these
      nuclei, as well as in the optic radiation (OR) and white matter underlying area
      17, both double-stained PV + CR or CR + CB and separate populations of PV-ir, CB
      ir and CR-ir neurons and fibres were observed. Unlike the thalamic regions, the
      SC showed some double-stained PV + CR and CR + CB neurons, scattered both in the
      superficial and deep layers. These findings are discussed in the light of similar
      observations recently reported from other regions of the human brain.

PMID- 9271193
TI  - Localization of two cholinergic markers, choline acetyltransferase and vesicular
      acetylcholine transporter in the central nervous system of the rat: in situ
      hybridization histochemistry and immunohistochemistry.
AB  - Choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT)
      are proteins that are required for cholinergic neurotransmission. Present
      knowledge concerning the organization of cholinergic structures has been derived
      primarily from immunohistochemistry for ChAT. In the present study, we
      investigated the distribution of mRNAs and the corresponding proteins for ChAT
      and VAChT by in situ hybridization histochemistry and immunohistochemistry. The
      patterns of distribution of perikarya containing ChAT mRNA. ChAT protein, VAChT
      mRNA and VAChT protein were similar in most regions, and co-localization in the
      same neuron of mRNAs for ChAT and VAChT, that of ChAT mRNA and ChAT protein, and
      that of VAChT mRNA and VAChT protein were demonstrated. However, in the cerebral
      cortex and hypothalamus, ChAT-immunoreactive perikarya were present, but they did
      not contain mRNAs for ChAT and VAChT, and VAChT protein. On the other hand, in
      the cerebellum, Purkinje cell bodies contained VAChT mRNA and VAChT protein, but
      they did not contain either ChAT mRNA or ChAT protein. Axon bundles were clearly
      revealed by immunohistochemistry for ChAT, but they were not detected by that for
      VAChT. Both ChAT and VAChT antibodies revealed preterminal axons and terminal
      like structures. In the forebrain, they were present in the olfactory bulb,
      nucleus of the lateral olfactory tract, olfactory tubercle, lateral septal
      nucleus, amygdala, hippocampus, neocortex, caudate-putamen, thalamus and median
      eminence of the hypothalamus. In the brainstem, they were localized in the
      superior colliculus, interpeduncular nucleus and some cranial nerve motor nuclei,
      and further in the ventral horn of the spinal cord. These results indicate
      strongly that ChAT and VAChT are expressed in most of the cholinergic neurons,
      and that immunohistochemistry for VAChT is as useful to detect cholinergic
      terminal fields as that for ChAT.

PMID- 9271195
TI  - Selective decline of 5-HT1A receptor binding sites in rat cortex, hippocampus and
      cholinergic basal forebrain nuclei during aging.
AB  - The effect of aging on 5-HT1A receptor binding in several forebrain areas
      associated with the basal forebrain cholinergic system was investigated in rats
      of 3-, 24- and 30-months-old by receptor autoradiography and biochemical binding
      assay using [3H]8-OH-DPAT as a ligand. Autoradiographic measurements demonstrated
      a marked region-specific decline of ligand binding in: (i) regions of the basal
      forebrain cholinergic cell groups, i.e. the medial septum, diagonal band nuclei
      and magnocellular nucleus basalis, (ii) the frontal and parietal neocortex and
      (iii) the dentate gyrus of the hippocampus. No change or only a slight decrease
      of the 5-HT1A receptor density was found in other areas investigated: the CA1 and
      CA3 sectors of hippocampus, the cingular and perirhinal cerebral cortex and the
      lateral septum. The autoradiographic findings were substantiated by the
      biochemical binding assay, which revealed a comparable loss of 5-HT1A receptor in
      the hippocampus and neocortex at the age of 30 months. The results clearly show
      that with increasing age the decrement of 5-HT1A receptor binding in the rat
      forebrain is remarkably region-selective and particularly affects the cholinergic
      cell groups that innervate cortex and hippocampus. This phenomenon appears to be
      especially significant in relation to the neuronal substrates underlying the age
      related alterations of mood and cognition.

PMID- 9271196
TI  - What nitrates tyrosine? Is nitrotyrosine specific as a biomarker of peroxynitrite
      formation in vivo?
AB  - Peroxynitrite (ONOO-) is a 'reactive nitrogen species' that can be formed (among
      other reactions) by combination of superoxide (O2.-) and nitric oxide (NO.)
      radicals. It is being increasingly proposed as a contributor to tissue injury in
      several human diseases. The evidence presented for peroxynitrite participation
      usually includes the demonstration of increased nitrotyrosine levels in the
      injured tissue. Indeed, this is often the only evidence presented: the assumption
      is that formation of nitrotyrosine is a biomarker specifically diagnostic of ONOO
      production. The present article examines this assumption and concludes that
      nitrotyrosine is a biomarker for 'nitrating species' rather than being specific
      for ONOO-.

PMID- 9271197
TI  - Hevamine, a chitinase from the rubber tree Hevea brasiliensis, cleaves
      peptidoglycan between the C-1 of N-acetylglucosamine and C-4 of N-acetylmuramic
      acid and therefore is not a lysozyme.
AB  - Hevamine is a chitinase from the rubber tree Hevea brasiliensis and belongs to
      the family 18 glycosyl hydrolases. In this paper the cleavage specificity of
      hevamine for peptidoglycan was studied by HPLC and mass-spectrometry analysis of
      enzymatic digests. The results clearly showed that the enzyme cleaves between the
      C-1 of a N-acetylglucosamine and the C-4 of a N-acetylmuramate residue. This
      means that hevamine, and very likely also other family 18 glycosyl hydrolases
      which cleave peptidoglycan, cannot be classified as lysozymes.

PMID- 9271198
TI  - Sequence and expression of a novel member (LTBP-4) of the family of latent
      transforming growth factor-beta binding proteins.
AB  - Overlapping cDNA clones from human heart and melanoma libraries were used to
      establish the 1587-residue sequence of a novel protein (LTBP-4) belonging to the
      family of extracellular microfibrillar proteins which also bind transforming
      growth factor-beta. LTBP-4 consists of 20 EG modules, 17 of them with a consensus
      sequence for calcium binding, 4 TB modules with 8 cysteines and several proline
      rich regions. Northern blots demonstrated a single 5 kb mRNA which is highly
      expressed in heart but also present in skeletal muscle, pancreas, placenta and
      lung. The modular structure predicts that LTBP-4 should be a microfibrillar
      protein which probably also binds TGF-beta.

PMID- 9271199
TI  - High-affinity binding of the yeast cis-Golgi t-SNARE, Sed5p, to wild-type and
      mutant Sly1p, a modulator of transport vesicle docking.
AB  - Docking of ER-derived vesicles to the cis-Golgi compartment in yeast requires
      vesicle and target membrane receptors (v-SNAREs and t-SNAREs) and the GTPase
      Ypt1p. The t-SNARE Sed5p is complexed with Sly1p in vivo. The mutant form Sly1
      20p rescues Ypt1p-lacking cells from lethality, suggesting an inhibitory function
      of Sly1p in v-SNARE/t-SNARE interaction. Using surface plasmon resonance
      spectroscopy, we found that Sed5p binds Sly1p and Sly1-20p with equally high
      affinity (K(D) = 5.13 x 10(-9) M and 4.74 x 10(-9) M, respectively). Deletion
      studies show that the N-terminal half of Sly1p rather than the C-terminus
      (harbouring the E532K substitution in Sly1-20p) is most critical for its binding
      to Sed5p. These data appear to argue for an active rather than an inhibitory role
      of Sly1p in vesicle docking.

PMID- 9271200
TI  - A novel antimicrobial peptide from the loach, Misgurnus anguillicaudatus.
AB  - A novel antimicrobial peptide, named misgurin, was isolated and characterized
      from the loach (mudfish), Misgurnus anguillicaudatus. The 21-amino-acid peptide
      with a molecular mass of 2502 Da was purified to homogeneity using a heparin
      affinity column and C18 reverse-phase and gel-permeation high-performance liquid
      chromatography. The complete amino acid sequence of misgurin, which was
      determined by an automated amino acid sequencer, was Arg-Gln-Arg-Val-Glu-Glu-Leu
      Ser-Lys-Phe-Ser-Lys-Lys-Gly-Ala-Ala-Ala-Arg- Arg-Arg-Lys. Misgurin is a strongly
      basic peptide which has 5 arginine and 4 lysine residues. Comparison of the amino
      acid sequence with those of other known antimicrobial peptides revealed that
      misgurin was a novel antimicrobial peptide. Misgurin showed a strong
      antimicrobial activity in vitro against a broad spectrum of microorganisms
      without significant hemolytic activity and was about 6 times more potent than
      magainin 2. Scanning electron microscopy confirmed that the peptide caused damage
      to the cell membrane by a pore-forming mechanism similar to that of magainin 2.
      This damage occurred at the minimal inhibition concentration (MIC), but at higher
      concentration than MIC it lysed the cell.

PMID- 9271201
TI  - Interaction of human retinal RGS with G-protein alpha-subunits.
AB  - A novel family of RGS proteins negatively regulates signaling via heterotrimeric
      G-proteins by accelerating the GTPase activity of G-protein alpha subunits. We
      have investigated interaction of human retinal RGS protein (hRGSr) with in vitro
      translated G(alpha) subunits: G(t alpha), G(i alpha1), G(o alpha) and G(s alpha).
      hRGSr binds well to G(t alpha), G(i alpha1) and G(o alpha) in the presence of
      AIF4-, but does not interact with G(s alpha). The N- and C-terminally truncated
      G(alpha) subunits interact with hRGSr similarly to the intact G(alpha)
      polypeptides. Analysis of interaction between hRGSr and G(o alpha)/G(s alpha)
      chimeras suggests that a region of G(o alpha), G(o alpha)22-212, contains major
      structural determinants for binding to RGS proteins.

PMID- 9271202
TI  - Lithium inhibits Alzheimer's disease-like tau protein phosphorylation in neurons.
AB  - In Alzheimer's disease, tau protein becomes hyperphosporylated, which can
      contribute to neuronal degeneration. However, the implicated protein kinases are
      still unknown. Now we report that lithium (an inhibitor of glycogen synthase
      kinase-3) causes tau dephosphorylation at the sites recognized by antibodies Tau
      1 and PHF-1 both in cultured neurons and in vivo in rat brain. This is consistent
      with a major role for glycogen synthase kinase-3 in modifying proline-directed
      sites on tau protein within living neurons under physiological conditions.
      Lithium also blocks the Alzheimer's disease-like proline-directed
      hyperphosphorylation of tau protein which is observed in neurons treated with a
      phosphatase inhibitor. These data raise the possibility of using lithium to
      prevent tau hyperphosphorylation in Alzheimer's disease.

PMID- 9271203
TI  - Alternative activation of transcriptional initiators in Drosophila melanogaster
      LINE promoters.
AB  - In the Drosophila I, F and Doc LINEs, basal transcription is ensured by the
      functional interaction of initiator sequences with intragenic regulatory segments
      (B regions) which comprise distinct functional modules. Removing the B regions,
      as changing their composition or location, allowed different activators to
      stimulate transcription from novel initiators both in Doc and F promoters. The
      use of distinct initiators plausibly reflects the assembly of transcriptional
      complexes in which TFIID assumes alternative spatial conformations. The response
      of I, F and Doc promoters to the same enhancer is significantly influenced by the
      number, position and type of core elements present.

PMID- 9271204
TI  - Yeast mitochondrial F1F0-ATPase: the novel subunit e is identical to Tim11.
AB  - We report here the identification of the novel subunit of the mitochondrial F1F0
      ATPase from Saccharomyces cerevisiae, ATPase subunit e. Yeast ATPase subunit e
      displays significant similarities in both amino acid sequence, properties
      (hydropathy and predicted coiled-coil structure) and orientation in the inner
      membrane, with previously identified mammalian ATPase subunit e proteins.
      Estimation of its native molecular mass and ability to be co-immunoprecipitated
      with a subunit of the F1-ATPase, demonstrate that subunit e is a subunit of the
      F1F0-ATPase. Stable expression of subunit e requires the presence of the
      mitochondrially encoded subunits of the F0-ATPase. Subunit e had been previously
      identified as Tim11 and was proposed to be involved in the process of sorting of
      proteins to the mitochondrial inner membrane.

PMID- 9271205
TI  - Stabilising and destabilising modifications of cysteines in the E. coli outer
      membrane porin protein OmpC.
AB  - Three sulfhydryl labels were used to modify two mutated sites, R37C and R74C in
      the eyelet of the outer membrane porin OmpC. Modification of R37C with the
      neutral groups Aldrithiol and bimane increases thermal stability but the
      negatively charged iodoacetate causes a decrease in thermal stability. The
      effects of substitution at R74C were less significant. Bimane labelling increases
      the voltage sensitivity and decreases the single channel conductance at R37C
      asymmetrically with smaller channels being recorded at cis negative voltages.
      Negatively charged acetate does not affect the voltage gating.

PMID- 9271206
TI  - Differential expression of genes coding for ABC transporters after treatment of
      Arabidopsis thaliana with xenobiotics.
AB  - ATP-binding cassette (ABC) transporters are thought to be involved in many
      cellular detoxification mechanisms. Performing a BLAST search, we found four
      distinct expressed sequence tags (EST) of Arabidopsis thaliana highly similar to
      the human and fungal glutathione-conjugate ABC transporters. We studied the
      expression of the corresponding genes in response to various xenobiotics in an
      effort to gain information on their function. The abundance of transcripts
      corresponding to one of the genes (EST1) was not affected by the various
      compounds tested, whereas the abundance of transcripts corresponding to the other
      three genes (EST2, EST3, EST4) was increased by 1-chloro-2,4-dinitrobenzene,
      primisulfuron and IRL 1803. Treatment of Arabidopsis with either primisufuron or
      IRL 1803 resulted in a more than 40-fold increase in EST2-specific transcripts.

PMID- 9271207
TI  - The yeast mic2 mutant is defective in the formation of mannosyl
      diinositolphosphorylceramide.
AB  - The mic2 mutation dominantly blocks formation of mannosyl
      diinositolphosphorylceramide, the most abundant sphingolipid of the yeast,
      Saccharomyces cerevisiae. Interestingly, lack of mannosyl
      diinositolphosphorylceramide is not lethal but is compensated for by increased
      amounts of inositolphosphorylceramide and mannosyl-inositolphosphorylceramide in
      the plasma membrane and Golgi of the mutant. The level of negatively charged
      phospholipids in the plasma membrane of the mic2 strain is markedly reduced; the
      sterol composition is not altered. In spite of dramatic changes of its lipid
      composition the mutant grows like wild type on complex and minimal media, under
      osmotic stress conditions, at low pH, and in the presence of high ionic strength.
      While sensitivity to several drugs is not altered, the mic2 mutant strain becomes
      resistant to the polyene antibiotic nystatin.

PMID- 9271208
TI  - Camptothecin-binding site in human serum albumin and protein transformations
      induced by drug binding.
AB  - Circular dichroism (CD) and Raman spectroscopy were employed in order to locate a
      camptothecin (CPT)-binding site within human serum albumin (HSA) and to identify
      protein structural transformations induced by CPT binding. A competitive binding
      of CPT and 3'-azido-3'-deoxythymidine (a ligand occupying IIIA structural sub
      domain of the protein) to HSA does not show any competition and demonstrates that
      the ligands are located in the different binding sites, whereas a HSA-bound CPT
      may be replaced by warfarin, occupying IIA structural sub-domain of the protein.
      Raman and CD spectra of HSA and HSA/CPT complexes show that the CPT-binding does
      not induce changes of the global protein secondary structure. On the other hand,
      Raman spectra reveal pronounced CPT-induced local structural modifications of the
      HSA molecule, involving changes in configuration of the two disulfide bonds and
      transfer of a single Trp-residue to hydrophilic environment. These data suggest
      that CPT is bound in the region of interdomain connections within the IIA
      structural domain of HSA and it induces relative movement of the protein
      structural domains.

PMID- 9271209
TI  - Structures of the O-antigens of Proteus bacilli belonging to OX group (serogroups
      O1-O3) used in Weil-Felix test.
AB  - Structures of the O-specific polysaccharide chains of lipopolysaccharides from
      Proteus group OX strains (serogroups O1-O3) used as antigens in Weil-Felix test
      for diagnosis of rickettsiosis, were established. From them, the acid-labile
      polysaccharide of Proteus vulgaris OX19 (O1) is built up of the following
      branched pentasaccharide repeating units connected via a phosphate group:
      [structure in text] where QuiNAc stands for 2-acetamido-2,6-dideoxyglucose (N
      acetylquinovosamine). The basis of serospecificity of the Proteus group OX
      antigens and their cross-reactivity with human anti-rickettsial antibodies is
      discussed.

PMID- 9271211
TI  - The MBP fusion protein restores the activity of the first phosphatase domain of
      CD45.
AB  - CD45 is a receptor-like protein tyrosine phosphatase critically involved in the
      regulation of initial effector functions in B- and T-cells. The protein comprises
      two phosphatase (PTP) domains in its cytoplasmic region. However, whether each
      PTP domain has enzyme activity by itself or whether both domains are required to
      build up a functional enzyme is unclear. We have studied different constructions
      of human CD45 comprising the two PTP domains, both separately and as a single
      protein, fused to maltose-binding protein (MBP). In apparent contrast with
      previous studies, we show that the first PTP domain of CD45 (when fused to MBP)
      may be a viable phosphatase in the absence of the second domain. Phosphatase
      activity resides in the monomeric form of the protein and is lost after
      proteolytic cleavage of the fusion partner, indicating that MBP specifically
      activates the first PTP domain. Furthermore, changes in the optimal pH for
      activity with respect to wild-type CD45 suggest that protein-protein interactions
      involving residues in the neighbourhood of the catalytic site mediate enzyme
      activation.

PMID- 9271210
TI  - Genomic organization and functional characterization of the mouse GalR1 galanin
      receptor.
AB  - Galanin mediates diverse physiological functions in digestive, endocrine, and
      central nervous systems through G-protein-coupled receptors. Two galanin
      receptors have been cloned but the gene structures are unknown. We report genomic
      and cDNA cloning of the mouse GalR1 galanin receptor and demonstrate that the
      coding sequence is uniquely divided into three exons encoding the N-terminal
      portion through the fifth transmebrane domain, the third intracellular loop, and
      the sixth transmembrane domain through the C-terminus. Functional analysis of the
      encoded cDNA revealed active ligand binding and intracellular signaling. The
      expression is detected in brain, spinal cord, heart and skeletal muscle.

PMID- 9271212
TI  - Evidence for light-dependent and light-independent protein dephosphorylation in
      chloroplasts.
AB  - A number of photosystem II (PSII) associated proteins, including core proteins
      D1, D2 and CP43, and several proteins of the LHCII complex, are phosphorylated by
      a thylakoid-bound, redox-regulated kinase(s). We demonstrate here that the
      compound propyl gallate is an effective inhibitor of LHCII phosphorylation in
      vivo while having little effect on PSII core protein phosphorylation. Using this
      inhibitor, we demonstrate that LHCII dephosphorylation is insensitive to light in
      vivo. Taken together with our previous conclusion (Elich et al., EMBO J. 12
      (1993) 4857-4862) that PSII core protein dephosphorylation is light-stimulated,
      our data suggest the presence of multiple phosphatases responsible for thylakoid
      protein dephosphorylation in vivo.

PMID- 9271213
TI  - Sense and antisense RNA for the membrane associated 40 kDa subunit M40 of the
      insect V-ATPase.
AB  - For the first time a cDNA encoding the membrane associated subunit M40 of an
      invertebrate V-ATPase has been isolated and sequenced, based on a cDNA library
      from larval midgut of the tobacco hornworm, Manduca sexta. Immunoblotting with
      monospecific antibodies raised against the recombinant M40 polypeptide
      demonstrated that it is a subunit of the insect plasma membrane V-ATPase. Since
      M40 subunits had been identified only in endosomal V-ATPases till now, this
      result indicates that they are constitutive members of all, endomembrane and
      plasma membrane V-ATPases. A phagemid clone representing a polyadenylated
      antisense transcript was also isolated and sequenced. Using RT-PCR, endogenous
      antisense RNA was detected in poly(A) RNA isolated from the larval midgut. Since
      Southern blots indicated a single gene locus, both the antisense RNA as well as
      the sense mRNA encoding subunit M40 seem to originate from the same gene.

PMID- 9271214
TI  - Differential translational initiation of lbp mRNA is caused by a 5' upstream open
      reading frame.
AB  - Expression of the luciferin-binding protein (LBP) from Gonyaulax polyedra is
      regulated by the circadian clock at the translational level. Here we report that
      in vitro translation of lbp mRNA results in the synthesis of two LBP variants of
      different sizes, which is shown to be due to translational initiation at
      different in-frame AUG codons on lbp mRNA. Differential initiation is caused by a
      small open reading frame (ORF, situated in the 5' untranslated region of lbp
      mRNA), which gives rise to a leaky scanning mechanism. In Gonyaulax, only one of
      these variants, which is produced by initiation from the first AUG of the lbp
      ORF, exhibits a circadian rhythm and is far more abundant during night phase.

PMID- 9271215
TI  - Comparison of PMM1 with the phosphomannomutases expressed in rat liver and in
      human cells.
AB  - Carbohydrate-deficient glycoprotein syndrome type I (CDGI) is most often due to
      phosphomannomutase deficiency; paradoxically, the human phosphomannomutase gene
      PMM1 is located on chromosome 22, whereas the CDGI locus is on chromosome 16. We
      show that phosphomannomutases present in rat or human liver share with
      homogeneous recombinant PMM1 several kinetic properties and the ability to form
      an alkali- and NH2OH-sensitive phosphoenzyme with a subunit mass of approximately
      30,000 Mr. However, they have a higher affinity for the activator mannose-1,6
      bisphosphate than PMM1 and are not recognized by anti-PMM1 antibodies, indicating
      that they represent a related but different isozyme. Phosphomannomutases belong
      to a novel mutase family in which the active residue is a phosphoaspartyl or a
      phosphoglutamyl.

PMID- 9271216
TI  - Evidence for a 65 kDa sulfonylurea receptor in rat pancreatic zymogen granule
      membranes.
AB  - In rat pancreatic zymogen granules (ZG), a K+ selective conductance which can be
      blocked by ATP has been characterized. Here we show that this pathway can be
      specifically blocked by glibenclamide. Using a rapid filtration assay, we also
      found specific binding of [3H]glibenclamide to a low-affinity site (Kd 5.6 +/-
      1.1 microM) in rat pancreatic zymogen granule membranes (ZGM). In photoaffinity
      labeling experiments with [3H]glibenclamide, a 65 +/- 1.5 kDa polypeptide was
      specifically labeled. Previously, a approximately 65 kDa mdr1 gene product has
      been demonstrated to be involved in the regulation of the K+ selective
      conductance of ZG. We conclude that this protein may be a subunit of, or
      associated with, a ZG K(ATP) channel.

PMID- 9271217
TI  - Bcl-2 antagonizes apoptotic cell death induced by two new ceramide analogues.
AB  - Ceramides which arise in part from the breakdown of sphingomyelin comprise a
      class of antiproliferative lipids and have been implicated in the regulation of
      programmed cell death better known as apoptosis. In the present study, two new
      synthetic ceramide analogues, N-thioacetylsphingosine and FS-5, were used in Molt
      4 cells to induce cell death. Besides their cytotoxic effects at concentrations >
      or = 14 microM the data obtained clearly show that both analogues induced
      apoptosis at concentrations below this critical concentration as assessed by
      trypan blue exclusion and cleavage of the death substrate poly-(ADP-ribose)
      polymerase (PARP). Additional experiments in bcl-2-transfected Molt 4 cells
      revealed that the apoptotic but not the lytic effects of the analogues were
      antagonized by the apoptosis inhibitor Bcl-2. Furthermore, neither N-thio
      acetylsphingosine nor FS-5 induced PARP cleavage in bcl-2-transfected Molt 4
      cells indicating that the induction of apoptotic cell death by cell permeable
      ceramides is not due to unspecific disturbance of the cell membrane.

PMID- 9271218
TI  - Specificity of different isoforms of protein phosphatase-2A and protein
      phosphatase-2C studied using site-directed mutagenesis of HMG-CoA reductase.
AB  - We have expressed the catalytic domain of Chinese hamster HMG-CoA reductase, and
      13 point mutations involving the region around the single phosphorylation site
      for AMP-activated protein kinase. After phosphorylation, these were used to test
      the specificity of isoforms of protein phosphatase-2A [bovine PP2A(C) (catalytic
      subunit) and PP2A1 (ABC heterotrimer)] and protein phosphatase-2C (human alpha;
      mouse alpha, beta1, beta2, beta3, beta4, beta5). PP2A1 had > 50-fold higher
      activity for HMG-CoA reductase variants than PP2A(C), but their relative
      selectivity for different variants was similar. Although the specificities of
      PP2A and PP2C were distinct, no dramatic differences in selectivity were observed
      between different PP2C isoforms.

PMID- 9271219
TI  - Transient-state and steady-state kinetics of the oxidation of aliphatic and
      aromatic thiols by horseradish peroxidase.
AB  - In the course of oxidation of thiols by peroxidases thiyl radicals are formed
      which are known to undergo several free-radical conjugative reactions, among
      others leading to hydrogen peroxide formation. The present paper for the first
      time presents a comparative transient-state and steady-state investigation of the
      reaction of 15 aliphatic and aromatic mono- and dithiols with horseradish
      peroxidase (HRP). Both sequential-stopped-flow spectrophotometric investigations
      of the reaction of HRP intermediates Compound I (k2) and Compound II (k3) with
      thiols and measurements of the overall thiol oxidation and the simultaneous
      oxygen consumption in the presence and absence of exogenously added hydrogen
      peroxide (10 microM) have been performed. With HRP as thiyl radical generator it
      was shown that three groups of thiols have to be distinguished: (i) Aromatic
      thiols (e.g. thiophenol, 2-mercaptopurine) were excellent electron donors of both
      Compounds (k2: 10(4)-10(7) M(-1) s(-1) and k3: 10(3)-10(6) M(-1) s(-1)); however,
      the overall reaction was shown to depend on addition of hydrogen peroxide,
      indicating insufficient peroxide regeneration by arylthiyl radicals. (ii)
      Aliphatic thiols which were extremely bad substrates (k3 < 10 M(-1) s(-1)) for
      HRP (e.g. homocysteine, glutathione) and/or have a pK(a,SH) > 9.5 (e.g. N
      acetylcysteine, alpha-lipoic acid) were also shown to depend on exogenously added
      H2O2 to maintain the peroxidasic reaction, whereas (iii) with those thiols with
      rates of k3 between 11 and 1600 M(-1) s(-1) (e.g. cysteine, cysteamine, cysteine
      methyl ester, cysteine ethyl ester) and/or with a pK(a,SH) < 8 (penicillamine)
      thiol oxidation was independent of exogenously added hydrogen peroxide,
      indicating sufficient hydrogen peroxide regeneration.

PMID- 9271220
TI  - In vivo translational efficiency of different hepatitis C virus 5'-UTRs.
AB  - Initiation of translation in hepatitis C virus (HCV) is dependent on the presence
      of an internal ribosome entry site (IRES) contained in its 341-nt-long 5'
      untranslated region (UTR). This region is very conserved among different isolates
      and has been used to classify HCV isolates in six different genotypes. These
      genotypes differ in nucleotide sequence that generally preserve the IRES
      structure. However, the small differences seen may be biologically and clinically
      significant as the HCV strains seem to differ from each other in several
      important ways, such as the behaviour of the viral infection and the response to
      interferon therapy. Therefore, differences in translational initiation efficiency
      amongst the various genotypes could provide an explanation for these phenomena.
      Using a bicistronic expression system we have compared the in vivo translational
      ability of the three most common European genotypes of HCV (1, 2, and 3). The
      results show that genotype 3 is less able than 1 and 2 to promote translation
      initiation. In addition, by site-directed mutagenesis of the sequence of the IRES
      domain III apical stem loop structure, we have shown that the conservation of the
      primary nucleotide sequence and not only the structure, is important for the
      conservation of IRES function.

PMID- 9271221
TI  - Poly(ethylene glycol)-lipid conjugates inhibit phospholipase C-induced lipid
      hydrolysis, liposome aggregation and fusion through independent mechanisms.
AB  - Poly(ethylene glycol)-phosphatidylethanolamine (PEG-PE) conjugates have been
      introduced in liposomal compositions. The resulting large unilamellar vesicles
      were subjected to the action of phospholipase C. Enzyme-promoted vesicle
      aggregation and fusion were assayed in liposomes containing various proportions
      of PEG-PE. At PEG-PE concentrations above 1 mol% the rate of phospholipid
      hydrolysis decreases, perhaps because the PEG moiety hinders the enzyme from
      reaching the membrane surface. At concentrations above 0.1 mol% vesicle
      aggregation occurs at a slower rate, presumably because of the repulsive barrier
      properties or surface-grafted PEG. Lipid mixing decreases in parallel with
      vesicle aggregation. Finally, liposomal fusion rates measured as mixing of
      vesicle aqueous contents are decreased at or even below 0.1 mol%. The latter
      inhibition is due, apart from the reduced rates of lipid hydrolysis, vesicle
      aggregation and lipid mixing, to a PEG-PE-based stabilization of the lipid
      bilayer structure. Thus the observed low rates of contents mixing arise from
      three combined and independent inhibitory effects of PEG-PE.

PMID- 9271222
TI  - Dioxygenation of N-linoleoyl amides by soybean lipoxygenase-1.
AB  - Anandamide, a novel neurotransmitter, has been reported to be dioxygenated by
      brain lipoxygenase [1,11]. Anandamides constitute a new class of neuroregulatory
      fatty acid amides. However, little is known about the enzymatic dioxygenation of
      these lipids. Therefore, we have tested several members of the neuroactive fatty
      acid amide class containing a 1Z,4Z-pentadiene system whether they could be
      dioxygenated by soybean lipoxygenase-1, which is a model enzyme for mammalian
      lipoxygenases. In this study it was found that lipoxygenase-1 converts N
      linoleoylethanolamide (ODNHEtOH), N-linoleoylamide (ODNH2), N
      linoleoylmethylamide (ODNHMe) and N,N-linoleoyldimethylamide (ODN(Me)2 into 13
      (S)-hydroperoxy-9Z,11E-octadeca-9,11-dienoyl amides derivatives. The apparent Km
      values for ODNHEtOH (23.6 +/- 3.7 microM), ODNH2 (8.60 +/- 0.65 microM) and
      linioleic acid (OD: 8.85 +/- 0.74 microM) are not significantly different. The
      k(cat) for ODNH2 (32.4 +/- 1.2 s(-1)) is twice as small as compared to the
      turnover numbers of the other substrates, viz. ODNHEtOH (61.6 +/- 5.0 s(-1)) and
      OD (54.4 +/- 2.0 s(-1). The results suggest that N-linoleoyl ethanolamide and N
      linoleoyl amide can be readily converted by lipoxygenases in vivo.

PMID- 9271223
TI  - Birch pollen profilin: structural organization and interaction with poly-(L
      proline) peptides as revealed by NMR.
AB  - The secondary structure of birch pollen profilin, a potent human allergen, was
      elucidated by multidimensional nuclear magnetic resonance (NMR), as a
      prerequisite to study the interaction of this profilin with ligands for its poly
      (L-proline) (PLP)-binding site. The chemical shifts of the 15N-labeled backbone
      amide groups were used to monitor complex formation with various PLP peptides.
      Titration with deca-L-proline (P10) yielded a KD of 0.2 mM. P8 was the shortest
      PLP to provoke a significant reaction. (GP5)3G bound significantly, confirming
      the interaction between profilins and the protein VASP containing this motif.
      Birch profilin interacted also with GP6GP5, found in the cyclase-associated
      protein (CAP), a suspected profilin ligand.

PMID- 9271224
TI  - Tissue-specific expression of the human laminin alpha5-chain, and mapping of the
      gene to human chromosome 20q13.2-13.3 and to distal mouse chromosome 2 near the
      locus for the ragged (Ra) mutation.
AB  - To investigate the function of the laminin alpha5-chain, previously identified in
      mice, cDNA clones encoding the 953-amino-acid carboxy terminal G-domain of the
      human laminin alpha5-chain were characterized. Northern blot analysis showed that
      the laminin alpha5-chain is expressed in human placenta, heart, lung, skeletal
      muscle, kidney, and pancreas. The human laminin alpha5-chain gene (LAMA5) was
      assigned to chromosome 20q13.2-q13.3 by in situ hybridization, and the mouse gene
      (Lama5) was mapped by linkage analysis to a syntonic region of distal chromosome
      2, close to the locus for the ragged (Ra) mutation.

PMID- 9271225
TI  - RIN14B: a pancreatic delta-cell line that maintains functional ATP-dependent K+
      channels and capability to secrete insulin under conditions where it no longer
      secretes somatostatin.
AB  - The delta-cell line RIN14B was characterized with regard to ATP-regulated K+
      (K(ATP)) channel activity and hormone release. By applying the patch-clamp
      technique, dose-response curves for ATP and the sulfonylurea tolbutamide were
      obtained in inside-out patches. The concentration causing half-maximal K(ATP)
      channel inhibition was found to be 23.7 and 27.6 microM for ATP and tolbutamide,
      respectively. ADP and diazoxide stimulated K(ATP) channel activity, an effect
      dependent on the presence of intracellular Mg2+. The stimulatory effect of
      diazoxide also required the presence of ATP. The kinetic properties of the K(ATP)
      channel were analysed in the presence of ATP, a combination of ADP and ATP and in
      nucleotide-free solutions. The distribution of K(ATP) channel open time could be
      described by a single exponential function with a time constant of approximately
      30 ms in nucleotide-free and in ATP-containing solutions. The presence of both
      ATP and ADP resulted in the appearance of an additional time constant of > 150
      ms. Single-channel unitary current-voltage (i-V) relation was characterised for
      the K((ATP) channel present in RIN14B cells. The slope conductance, measured at
      the reversal potential was found to be 19.1 +/- 2.4 pS. The permeability for K+
      ions was calculated to be 0.31 x 10(-13) cm3 x s(-1). We have not been able to
      confirm the somatostatin releasing profile of the RIN14B cells using
      radioimmunoassays, nor could we find positive somatostatin stain with
      immunocytochemical techniques. We conclude that the RIN14B cell line, previously
      characterized as a somatostatin-secreting cell line, contains K(ATP) channels
      with properties closely resembling the K(ATP) channel described in the pancreatic
      beta-cell. However, the cell line appears to have dedifferentiated with regard to
      the ability to secrete somatostatin, maintaining the highly differentiated
      function of both insulin biosynthesis and exocytosis.

PMID- 9271226
TI  - Glucose activation of the yeast plasma membrane H+-ATPase requires the ubiquitin
      proteasome proteolytic pathway.
AB  - Glucose triggers transcriptional and post-transcriptional mechanisms that
      increase the level and activity of Saccharomyces cerevisiae plasma membrane H+
      ATPase. We have studied the post-transcriptional activation of the enzyme by
      glucose and have found that Rsp5, a ubiquitin-protein ligase enzyme, Ubc4, a
      ubiquitin-conjugating enzyme, and the 26S proteasome complex are implicated in
      this activation. These results suggest that ATPase activation by glucose requires
      the ubiquitin-proteasome proteolytic pathway. This is supported by the fact that
      over-expression of the ubiquitin-specific protease Ubp2, which cleaves ubiquitin
      from its branched conjugates, inhibits this activation. We propose that glucose
      triggers degradation of an inhibitory protein resulting in enzyme activation.

PMID- 9271227
TI  - A common core for binding single-stranded DNA: structural comparison of the
      single-stranded DNA-binding proteins (SSB) from E. coli and human mitochondria.
AB  - The crystal structure of the DNA-binding domain of E. coli SSB (EcoSSB) has been
      determined to a resolution of 2.5 A. This is the first reported structure of a
      prokaryotic SSB. The structure of the DNA-binding domain of the E. coli protein
      is compared to that of the human mitochondrial SSB (HsmtSSB). In spite of the
      relatively low sequence identity between them, the two proteins display a high
      degree of structural similarity. EcoSSB crystallises with two dimers in the
      asymmetric unit, unlike HsmtSSB which contains only a dimer. This is probably a
      consequence of the different polypeptide chain lengths in the EcoSSB
      heterotetramer. Crucial differences in the dimer-dimer interface of EcoSSB may
      account for the inability of EcoSSB and HsmtSSB to form cross-species
      heterotetramers, in contrast to many bacterial SSBs.

PMID- 9271228
TI  - High-level expression of human c-Src can cause a spherical morphology without
      loss of anchorage-dependent growth of NIH 3T3 cells.
AB  - To investigate whether overexpression of human c-Src leads to cell rounding in
      anchorage-dependent NIH 3T3 fibroblasts, we have established c-Src-inducible cell
      lines using a lac repressor-operator system. RN1 cells, which expressed c-Src at
      a high level after induction, exhibited a spherical morphology and ceased to grow
      in monolayer culture. RN1 cells, however, exhibited neither focus-forming ability
      nor anchorage-independent growth potential with or without induction. Induced RN1
      c-Src was phosphorylated at Ser75, a previously reported spherical cell
      associated site, and at Tyr419. These data demonstrated for the first time that
      highly elevated human c-Src tyrosine kinase activity can cause NIH 3T3 cells to
      have a spherical morphology without loss of anchorage-dependent growth. The
      inducible cell line should be useful to study the mechanism for cell rounding by
      c-Src.

PMID- 9271229
TI  - Defective cell migration in an ovarian cancer cell line is associated with
      impaired urokinase-induced tyrosine phosphorylation.
AB  - The urokinase receptor (u-PAR), a protein anchored to cell membrane by a glycosyl
      phosphatidylinositol, plays a central role in cancer cell invasion and metastasis
      by binding urokinase plasminogen activator (u-PA), thereby facilitating
      plasminogen activation. Plasmin can promote cell migration either directly or by
      activating metalloproteinases that degrade some of the components of the extra
      cellular matrix. However, the IGR-OV1-Adria cell line contains the u-PAR but does
      not migrate even in the presence of exogenous u-PA, although the parental IGR-OV1
      cell line migrates normally in the presence of u-PA. We therefore investigated
      the role of cell signalling for u-PA induced cell locomotion. We show that cell
      migration induced by u-PA-u-PAR complex is always associated with tyrosine kinase
      activation for the following reasons: (1) the blockade of the u-PAR by a chimeric
      molecule (albumin-ATF) inhibits not only the u-PA-induced cell migration, but
      also the signalling in IGR-OV1 line; (2) the binding of u-PA to u-PAR on non
      migrating IGR-OV1-Adria cells was not associated with tyrosine kinase activation;
      (3) the inhibition of tyrosine kinase also blocked cell migration of IGR-OV1.
      Therefore tyrosine kinase activation seems to be essential for the u-PA-induced
      cell locomotion possibly by the formation of a complex u-PAR-u-PA with a protein
      whose transmembrane domain can ensure cell signalling. Thus, IGR-OV1 and IGR-OV1
      Adria cell lines represent a good model for the analysis of the mechanism of u-PA
      u-PAR-induced cell locomotion.

PMID- 9271230
TI  - BIT, an immune antigen receptor-like molecule in the brain.
AB  - We previously found a brain-specific glycoprotein in the rat brain. It
      postnatally increases and is rich in the mature brain. We cloned cDNA of this
      protein. It is composed of a signal peptide, a V-type immunoglobulin domain, two
      C1-type immunoglobulin domains, a transmembrane segment and a cytoplasmic region
      containing two tyrosine-based activation motifs (TAM) that are variants of the
      antigen receptor signaling motifs. The overall structure is similar to those of
      immune antigen receptors. This molecule, BIT (brain immunoglobulin-like molecule
      with TAMs), is a major endogenous substrates of brain tyrosine kinases in vitro.
      Cerebral cortical neurons could extend their neurites on BIT-coated substrate and
      anti-BIT monoclonal antibody specifically inhibited the effect. These findings
      and our recent study concerning BIT signal transduction mechanism suggest that
      BIT, an immune antigen receptor-like molecule of the brain, functions as a
      membrane signaling molecule that may participate in cell-cell interaction.

PMID- 9271231
TI  - Circular dichroism spectroscopy of Lucina I hemoglobin.
AB  - The monomeric hemoglobin from the mollusc Lucina pectinata (HbI) represents an
      interesting model system for the study of heme-related circular dichroic (CD)
      bands in view of the highly asymmetric distribution of aromatic residues around
      the heme pocket revealed by the X-ray crystal structure. The CD spectra of both
      ferrous and ferric HbI derivatives exhibit negative CD bands in the Soret and
      ultraviolet region with an enhanced ellipticity of the heme N and L bands in the
      near-UV region. In contrast, the magnitude of the Cotton effect in the visible
      and Soret regions is comparable to that observed in other hemoproteins. The
      spectrum of the carbon monoxide derivative shows a surprising similarity with
      that observed for the soybean leghemoglobin carbon monoxide adduct. A common
      structural feature in the two proteins is the presence in the distal pocket of
      two Phe residues (B9 and B10) the aromatic rings of which are perpendicular to
      the heme plane.

PMID- 9271233
TI  - Substrate binding to the inactive mutants of Streptomyces sp. N174 chitosanase:
      indirect evaluation from the thermal unfolding experiments.
AB  - Oligosaccharide binding to chitosanase from Streptomyces sp. N174 was indirectly
      evaluated from thermal unfolding experiments of the protein. Thermal unfolding
      curves were obtained by fluorescence spectroscopy in the presence of D
      glucosamine oligosaccharides ((GlcN)n, n = 3, 4, 5, and 6) using the inactive
      mutant chitosanase in which the catalytic residue, Glu22, is mutated to glutamine
      (E22Q), aspartic acid (E22D), or alanine (E22A). The midpoint temperature of the
      unfolding transition (Tm) of E22Q was found to be 44.4 degrees C at pH 7.0.
      However, the Tm increased upon the addition of (GlcN), by 1.3 degrees C (n = 3),
      2.5 degrees C (n = 4), 5.2 degrees C (n = 5), or 7.6 degrees C (n = 6). No
      appreciable change in Tm was observed when (GlcNAc)6 was added to E22Q. The
      effect of (GlcN)n on the thermal stability was examined using the other protein,
      RNase T1, but the oligosaccharide did not affect Tm of the protein. Thus, we
      concluded that the stabilization effect of (GlcN)n on the chitosanase results
      from specific binding of the oligosaccharides to the substrate binding cleft.
      When E22D or E22A was used instead of E22Q, the increases in Tm induced by
      (GlcN)6 binding were 2.7 degrees C for E22D and 4.2 degrees C for E22A. In E22D
      or E22A, interaction with (GlcN)6 seems to be partly disrupted by a
      conformational distortion in the catalytic cleft.

PMID- 9271232
TI  - P2X7 purinoceptor expression in Xenopus oocytes is not sufficient to produce a
      pore-forming P2Z-like phenotype.
AB  - The purinergic rP2X7 receptor expressed in a number of heterologous systems not
      only functions as a cation channel but also gives rise to a P2Z-like response,
      i.e. a reversible membrane permeabilization that allows the passage of molecules
      with molecular masses of > or = 300 Da. We investigated the properties of rP2X7
      receptors expressed in Xenopus oocytes. In two-electrode voltage-clamp
      experiments, ATP or BzATP caused inward currents that were abolished or greatly
      diminished when NMDG+ or choline replaced Na+ as the principal external cation.
      In fluorescent dye experiments, BzATP application did not result in entry of the
      fluorophore YO-PRO-1(2+). Thus, rP2X7 expression in Xenopus oocytes does not by
      itself give rise to the pore-forming P2Z phenotype, suggesting that ancillary
      factors are involved.

PMID- 9271234
TI  - Leptin inhibits glycogen synthesis in the isolated soleus muscle of obese (ob/ob)
      mice.
AB  - The ob gene product, leptin, causes significant and dose-dependent inhibition of
      basal and insulin-stimulated glycogen synthesis in isolated soleus muscle from
      ob/ob mice, and a smaller, non-significant inhibition in muscle from wild-type
      mice. Leptin had no inhibitory effect on glycogen synthesis in soleus muscle from
      the diabetic (db/db) mice, which lack the functional leptin receptor. The full
      length leptin receptor (Ob-Rb), is expressed in soleus muscle of both ob/ob and
      wild-type mice, however with no detectable differences in expression level. These
      results suggest that hyperleptinaemia may attenuate insulin action on glucose
      storage in skeletal muscle.

PMID- 9271235
TI  - Mastoparan and Rab3AL peptide potentiation of calcium-independent secretory
      activity in rat melanotrophs is inhibited by GDPbetaS.
AB  - The whole-cell patch-clamp membrane capacitance measurement was used to monitor
      secretory activity in rat melanotrophs, while rab3AL, putative effector domain
      peptides of Rab3 small GTPases (20-30 kDa), were introduced into cytosol. In
      melanotrophs dialyzed with calcium free solutions membrane capacitance tends to
      decrease slightly. This decrease is further potentiated with GDPbetaS (500
      microM). We found that rab3AL (100 microM) stimulated secretory activity in the
      absence of calcium. The rab3AL response was qualitatively comparable to the
      response to mastoparan (1 microM), an activator of certain heterotrimeric GTP
      binding proteins. Interestingly, inclusion of GDPbetaS (500 microM) resulted in a
      blockade of both rab3AL and mastoparan induced responses. We conclude that rab3AL
      and mastoparan induce calcium-independent stimulation of secretory activity in
      rat melanotrophs by activation of a downstream heterotrimeric GTP-binding
      protein.

PMID- 9271236
TI  - Remarkably slow folding of a small protein.
AB  - Equilibrium denaturation of the 72 amino acid alpha/beta-protein MerP, by acid,
      guanidine hydrochloride, or temperature, is fully reversible and follows a two
      state model in which only the native and unfolded states are populated. A cis
      trans equilibrium around a proline peptide bond causes a heterogeneity of the
      unfolded state and gives rise to a slow- and a fast folding population. With a
      rate constant of 1.2 s(-1) for the major fast folding population, which has none
      of the common intrinsically slow steps, MerP is the slowest folding protein of
      this small size yet reported.

PMID- 9271237
TI  - Further studies on the recoupling effect of 6-ketocholestanol upon oxidative
      phosphorylation in uncoupled liver mitochondria.
AB  - The effect of 6-ketocholestanol was studied on CCCP-induced uncoupling in liver
      mitochondria, submitochondrial particles and cytochrome oxidase proteoliposomes.
      It was found that 6-ketocholestanol prevents and reverses uncoupling induced by
      nM concentrations of CCCP on the three systems assayed. As it was reported on
      kidney mitochondrial membranes [Chavez et al. (1996) FEBS Lett. 379, 305-308],
      the recoupling effect caused by 6-ketocholestanol on submitochondrial particles
      and proteoliposomes could be due to a diminution of membrane fluidity.

PMID- 9271238
TI  - Overexpression of the mouse dishevelled-1 protein inhibits GSK-3beta-mediated
      phosphorylation of tau in transfected mammalian cells.
AB  - Tau is a neuronal microtubule-associated protein whose function is modulated by
      phosphorylation. GSK-3beta is a tau kinase. GSK-3beta is part of the wingless
      signalling pathway and stimulation by wingless is predicted to down-regulate GSK
      3beta activity. In Drosophila imaginal disc cells, overexpression of dishevelled,
      a component of the wingless pathway, mimics the wingless signal. We have
      therefore studied the effect that overexpression of the murine dishevelled-1
      protein has on GSK-3beta-mediated phosphorylation of tau in transfected CHO
      cells. We find that co-transfection with dishevelled-1 is inhibitory to GSK-3beta
      mediated tau phosphorylation. Tau is hyperphosphorylated in Alzheimer's disease
      and the possible relevance of these findings to Alzheimer's disease pathogenesis
      are discussed.

PMID- 9271239
TI  - Deletion of the yeast homologue of the human gene associated with Friedreich's
      ataxia elicits iron accumulation in mitochondria.
AB  - Deletion of YDL120, the yeast homologue of the human gene responsible for
      Friedreich's ataxia, elicits decreased cellular respiration associated with
      decreased cytochrome c oxidase activity and, in certain nuclear backgrounds,
      mitochondrial DNA is lost. In the null mutants, the cellular growth is highly
      sensitive to oxidants, such as H2O2, iron and copper. However, only ferrous
      sulfate elicits loss of mitochondrial DNA. Mitochondria of the null mutants
      contain 10 times more iron than wild-type. The neurodegeneration observed in
      Friedreich's ataxia can be well explained on the basis of a mitochondrial iron
      overload responsible for an increased production of highly toxic free radicals.

PMID- 9271240
TI  - Continuous hepatocyte growth factor supply prevents lipopolysaccharide-induced
      liver injury in rats.
AB  - We present a rat model in which continuous supply of hepatocyte growth factor
      (HGF) prevents liver injury induced by carbon tetrachloride (CCl4) and E. coli
      011:B4 lipopolysaccharide (LPS). Rat fibroblasts genetically modified to secrete
      rat HGF were implanted in syngenic rat spleen 7 days before administration of the
      hepatotoxins. Rats with HGF-secreting fibroblasts in the spleen showed a dramatic
      resistance to CCl4- and LPS-induced liver injury. In the LPS-induced liver injury
      model, blood chemical analysis revealed that the increase in serum glutamic
      oxalacetic transaminase level and the decrease in blood sugar level were
      remarkably suppressed in rats with HGF-secreting cells in the spleen. Most
      importantly, their survival rate was greatly improved compared to other control
      groups of rats. Thus our results indicate a new role of HGF in liver protection
      during endotoxemia and convey important clinical implications for developing new
      therapeutic modalities in the treatment of liver failure caused by endotoxemia.

PMID- 9271241
TI  - RAP1-like binding activity in islet cells corresponds to members of the Sp1
      family of transcription factors.
AB  - Deletion and mutational analyses of the gastrin promoter have identified a
      binding site for the yeast transcription factor RAP1 relevant for transcriptional
      activation in islet cells. We here report that the mammalian transcription
      factors binding to this site in islet cells are the Sp transcription factor
      members Sp1 and Sp3. Furthermore, functional analyses revealed Sp1- and Sp3
      mediated transcriptional activation of gastrin. These data reveal that the zinc
      finger proteins Sp1 and Sp3 do have similar binding specificities as the
      multifunctional yeast RAP1 protein.

PMID- 9271242
TI  - Ligand-binding specificity of human fibroblast growth factor receptor-3 IIIc.
AB  - Earlier studies indicated that human fibroblast growth factor receptor (FGFR)-3
      IIIc was activated equally well by both FGF-1 and FGF-2. In contrast, murine FGFR
      3 IIIc was preferentially activated by FGF-1. To address this issue, we
      determined the ligand-binding specificity of human FGFR-3 IIIc in comparison with
      human FGFR-1 IIIc. By equilibrium binding human FGFR-3 IIIc preferentially bound
      FGF-1 with high affinity, whereas FGFR-1 IIIc bound both FGF-1 and -2 with high
      affinity. By competition binding using FGF-1, -2, -4, or -6, FGF-1 competed more
      efficiently than the other FGFs. These results suggest that like the murine FGFR
      3 III, FGF-1 is a preferred ligand for human FGFR-3 IIIc.

PMID- 9271243
TI  - Prolonging the circulation time and modifying the body distribution of
      intravenously injected polystyrene nanospheres by prior intravenous
      administration of poloxamine-908. A 'hepatic-blockade' event or manipulation of
      nanosphere surface in vivo?
AB  - Intravenously injected uncoated small (60 nm) and large (250 nm) size model
      polystyrene particles (which are cleared rapidly from the blood by macrophages of
      the reticuloendothelial system) can be converted to long-circulatory and
      splenotropic particles in vivo, respectively, if such particles are injected
      shortly (up to 3 h) after an appropriate dose of the block polymer non-ionic
      surfactant, poloxamine-908. Evidence indicates that small and large size
      polystyrene beads can acquire a coating of poloxamine-908 and/or poloxamine
      protein complexes in vivo. The adsorption of such complexes on to the bead
      surface could explain their altered body distribution since small and large size
      polystyrene beads that were precoated with poloxamine-908 exhibit similar
      biodistribution following i.v. injection.

PMID- 9271244
TI  - Transepithelial fate of bilirubin in the isolated rat kidney.
AB  - The renal handling of bilirubin in the rat was studied using an isolated kidney
      preparation by means of the determination of total pigment concentration decay in
      the perfusion medium and its renal clearance. Unconjugated bilirubin was
      incorporated in the perfusate at a concentration of about 4 microg/ml. In order
      to establish the potential role of secretion in renal handling of the pigment,
      experiments were also performed incorporating in the perfusate different doses of
      nicotinic acid (NA) (0.1 and 1.0 mM final concentration), which is considered an
      alternative substrate for the organic anion transport system, or probenecid
      (Prob) (0.1 and 1.0 mM final concentration), the classical inhibitor of organic
      anion transport process. The magnitude of pigment uptake from the perfusion
      medium, estimated by a first order exponential decay constant, was decreased in a
      dose-dependent way by NA (40 and 76% decrease for 0.1 and 1.0 mM of NA,
      respectively) and Prob (57 and 88% decrease for 0.1 and 1.0 mM of Prob,
      respectively). NA and Prob also induced a diminution in the ratio of pigment
      renal clearance to glomerular filtration rate (24 and 48% decrease for 0.1 and
      1.0 mM of NA and 52 and 55% decrease for 0.1 and 1.0 mM of Prob). Based on these
      findings, it can be proposed that tubular secretion through the proximal cells
      contributes significantly to renal pigment depuration. In order to establish the
      possible contribution of cellular metabolism to the secretory process, a
      different set of experiments was conducted. The content of bilirubin mono and
      diconjugates (BMC and BDC) were determined in urine, in arterial and venous
      samples and in renal cortex. Studies performed using either an open or a closed
      circulating system, revealed that after conjugation in the renal cell, pigment
      derivatives can be secreted into both the tubule and the venous compartments.
      Total bilirubin concentration as well as the relative content of BMC and BDC in
      urine increased over time, representing the sum of both conjugates about 50% of
      the total pigment excreted by the end of experiments. Consequently, our results
      support the existence of a tubular transepithelial transport of bilirubin,
      playing the metabolism of the pigment an important role in this process.

PMID- 9271246
TI  - Sensory perception and transduction of UV-B radiation by the ciliate Blepharisma
      japonicum.
AB  - A key question to answer studying the biological effects of ultraviolet radiation
      on planktonic micro-organisms is whether they can perceive UV-B radiation as a
      sensory signal, likewise they do with visible light. We have faced this problem
      performing an individual-cell analysis of Blepharisma japonicum photomotile
      responses to UV-B stimuli. Our results on spectral responsiveness and on the
      effects of a photoresponse inhibitor indicate that B. japonicum is capable to
      perceive and transduce UV-B radiation as an environmental sensory stimulus, which
      it escapes from gathering in shadowed areas. Similar UV-B avoidance motile
      reactions could serve as a behavioural defence mechanism contributing to avoid
      harmful overexposure to UV-B.

PMID- 9271245
TI  - Alterations in the ganglioside composition of rat cortical brain slices during
      experimental lactic acidosis: implications of an enzymatic process independent of
      the oxidative stress.
AB  - Several in vitro studies have shown that lactic acidosis plays a role in brain
      damage by enhancing free radical formation and lipid peroxidation. The purpose of
      this study was to determine whether gangliosides are affected by lactic acid
      induced oxidation in rat brain tissues. Cortical brain slices were incubated at
      37 degrees C for 5 or 17 h in Krebs-Ringer buffer containing 20 mM lactic acid
      (final pH 5.5) previously equilibrated with 100% O2. Damage from lipid
      peroxidation was estimated by measurement of thiobarbituric acid-reactive
      substances (TBARS) and analysis of polyunsaturated fatty acids (PUFAs).
      Gangliosides were studied by high-performance thin-layer chromatography.
      Incubation with lactic acid induced overproduction of TBARS, whereas PUFAs were
      only slightly degraded, even after 17 h of incubation. However, the major
      modifications in the ganglioside profile occurred after 17 h of incubation.
      Gangliosides GD1a and GT1b decreased in conjunction with a substantial increase
      in the GM1 percentage. The addition of butylated-hydroxytoluene and
      desferrioxamine in the incubation medium, or incubation under 100% nitrogen,
      abolished TBARS production but not the ganglioside modifications, indicating that
      the change in ganglioside distribution was not related to oxidative stress
      induced by lactic acid. To investigate the possibility of an enzymatic process
      activated by the pH shift, slices were incubated with lactic acid in presence of
      2,3-dehydro-2-deoxy-N-acetylneuraminic acid, a specific inhibitor of sialidase.
      In these conditions, no change in gangliosides profile occurred. These results
      demonstrate that sialidase is responsible for the alterations in the gangliosides
      composition of rat cortical brain slices during lactic acidosis.

PMID- 9271247
TI  - N-acyl amino acid biosynthesis in marine bacterium, Deleya marina.
AB  - We reported previously that the marine bacterium, Deleya marina (ATCC 25374),
      produced N-acyl leucine and isoleucine, in which nonhydroxy fatty acid was linked
      to alpha-amino group of amino acid. Further analysis of bacterium lipids revealed
      the additional production of N-acyl ornithine. The N-acyl ornithine had a 3
      hydroxy fatty acid linked by an amide bond to a-amino group of ornithine and a
      nonhydroxy fatty acid esterified to the hydroxy group of the 3-hydroxy fatty
      acid. N-acyl ornithine was located in the cell membrane and N-acyl leucine and
      isoleucine in cytoplasm. N-acyl ornithine is thought to be a functional analogue
      of phosphatidylethanolamine (PE) because of their similar structure. PE
      replacement into N-acyl ornithine in the cell membrane under phosphate-limited
      conditions was observed with other bacteria, so we anticipated the
      nonbiosynthesis of N-acyl ornithine under phosphate-sufficient conditions. We did
      not anticipate that N-acyl leucine and isoleucine in cytoplasm, whose structure
      is dissimilar to that of PE, would be replaced into PE in the cell membrane.
      Neither N-acyl leucine, N-acyl isoleucine, nor N-acyl ornithine was
      biosynthesized under phosphate-sufficient condition. Thus, we report here for the
      first time that N-acyl amino acids in cytoplasm were not biosynthesized under
      phosphate-sufficient conditions.

PMID- 9271248
TI  - Oxidation of carotenoids by free radicals: relationship between structure and
      reactivity.
AB  - The relationship between structure and reactivity is reported for a collection of
      carotenoids in solution reacted with oxidants generated by a modified Fenton
      process or with peroxyl radicals generated via the azo-initiators AMVN and AIBN.
      The initial rates of oxidation were in the order: lycopene > beta,beta-carotene,
      zeaxanthin > echinenone, isozeaxanthin > astaxanthin, canthaxanthin. The
      oxidative degradation caused rapid bleaching, due to disruption and breakdown of
      the polyene chromophore. A number of reaction mechanisms are likely to be
      involved. Isozeaxanthin, canthaxanthin and astaxanthin, in which the C-4 and C-4'
      positions are occupied by functional groups, react more slowly than beta,beta
      carotene and zeaxanthin, in which this position is free. Products such as the 4
      methoxy (or 4-ethoxy) and 4,4'-dimethoxy (or 4,4'-diethoxy) derivatives were
      isolated from reactions of beta,beta-carotene with peroxyl radicals in the
      presence of methanol or ethanol. Electron density calculations suggest that the
      different reactivities cannot be attributed solely to differences in electron
      distribution along the polyene chain of the different chromophores, which would
      alter the susceptibility to free-radical addition to the conjugated double-bond
      system. Other reactions must therefore be considered, including hydrogen
      abstraction from positions allylic to the polyene chain (C-4 of beta,beta
      carotene and its derivatives, and of lycopene). Lycopene, lutein and zeaxanthin
      all reacted rapidly with oxidising agents, so these dietary carotenoids must also
      be considered as potential antioxidants.

PMID- 9271249
TI  - Chromatographic and spectroscopic assignment of thiol induced cycloaromatizations
      of enediyne in neocarzinostatin.
AB  - Neocarzinostatin is an enediyne antitumor antibiotic. Upon attack by a thiol, the
      enediyne nucleus is cycloaromatized into two stable 1:1 thiol adducts. After
      analyzing products from various thiols, the chromatographic and spectroscopic
      characters that associate only with the cyclized aromatic moiety from enediyne
      nucleus were assigned. Based on HPLC analysis we have derived, products from
      picomole ranges of the drug sample can be detected. Confirming the type of
      cycloaromatization at nanomole ranges can be achieved by photodiode array UV
      spectroscopy. Three-dimensional fluorogram presents ten times more sensitive
      identification. The method provides a sensitive tool for massive screening study
      in microscale.

PMID- 9271250
TI  - The enantiomeric purity of alcohols formed by enzymatic reduction of ketones can
      be improved by optimisation of the temperature and by using a high co-substrate
      concentration.
AB  - The stereoselective reduction of ketones by alcohol dehydrogenase from
      Thermoanaerobium brockii was studied in organic reaction media. 2-Propanol was
      used as co-substrate to regenerate the coenzyme NADPH. The enantiomeric excess of
      the alcohol formed from the ketone decreased during the course of the reaction
      (from 53 to 0% e.e. in the formation of (R)-2-butanol). This was interpreted as
      being due to the reversibility of all the reactions involved. By using a large
      excess of 2-propanol this effect was suppressed. In the reduction of 2-butanone
      to (R)-2-butanol, the enantiomeric excess increased with increasing temperature,
      but in the reduction of 2-pentanone to (S)-2-pentanol the enantiomeric excess
      decreased with increasing temperature. The data were evaluated in terms of free
      energy of activation of the reaction pathways leading to the different possible
      products.

PMID- 9271251
TI  - Melanin formation in the inner ear is catalyzed by a new tyrosine hydroxylase
      kinetically and structurally different from tyrosinase.
AB  - Detergent solubilized extracts of the cochleae of adult gerbils (Meriones
      unguiculatus) contain a tyrosine hydroxylase activity measurable by the
      radiometric method of Pomerantz. This activity is not related to Fenton-type
      reactions, since it is not inhibited by free radical scavengers and is heat and
      protease sensitive. It does not appear to be related to a peroxidase (EC
      1.11.1.7) since it is neither dependent on H2O2, nor inhibited by catalase (EC
      1.11.1.6). The involvement of a tyrosine hydroxylase (EC 1.14.16.2) related to
      catecholamine synthesis is also unlikely, since the activity is highly sensitive
      to 2-mercaptoethanol and is not increased by addition of tetrahydrobiopterin. The
      activity in crude inner ear extracts displayed an unusual maturation behaviour,
      with a slow activation upon aging at 4 degrees C. Fully active enzyme displayed
      Michaelis-Menten kinetics, with a Km for L-tyrosine of 47 microM. Cochlear
      tyrosine hydroxylase, but not melanoma tyrosinase (EC 1.14.18.1), was inhibited
      by o-phenanthroline, and was not dependent on L-DOPA as cofactor for full
      enzymatic activity. Crude extracts were also able to catalyze L-DOPA oxidation
      and melanin formation from either L-tyrosine or L-DOPA. The tyrosine hydroxylase,
      DOPA oxidase and melanin formation activities most probably resided in the same
      molecule, as suggested by inhibition studies. A tyrosine hydroxylase and melanin
      formation activity with identical properties was found in primary cultures of
      stria vascularis melanocytes. Immunochemical evidence confirmed the absence of
      either the tyrosinase encoded for by the albino locus, or the tyrosinase
      isoenzyme TRP1, encoded for by the brown locus. Conversely, an immunorreactive
      band of molecular weight 70 kDa was specifically recognized by a tyrosinase
      polyclonal antiserum in Western blot experiments. These results prove that
      melanogenesis in the cochlea, and likely in other extracutaneous locations such
      as the brain, is catalyzed by enzymatic systems different from, but related to
      tyrosinase.

PMID- 9271252
TI  - Generation of nitro and superoxide radical anions from 2,4,6
      trinitrobenzenesulfonic acid by rat gastrointestinal cells.
AB  - Reactive oxygen and nitrogen species have been implicated in the inflammation of
      the gastrointestinal tract. The objective of this study was to investigate
      mechanisms of free radical formation from the colitis inducer 2,4,6
      trinitrobenzene sulfonic acid (TNBS). We showed that TNBS was rapidly metabolized
      to TNBS nitro radical anion via metabolic reduction by
      flavinmononucleotide/NADPH, xanthine/xanthine oxidase as well as the rat small
      intestine and colon. TNBS nitro radical anion was directly detected with electron
      paramagnetic resonance (EPR) spectroscopy. EPR spectra of TNBS nitro radical
      anion showed hyperfine coupling constants from the proximal nitrogen, two
      hydrogens and the two distal nitrogens with respective magnitudes of a(N)(4) =
      9.7 G; a(H)(3,5) = 3.2 G (2); and a(N)(2,6) = 0.25 G. EPR spin trapping using 5.5
      dimethyl-1-pyrroline N-oxide in aerobic incubations of isolated enterocytes (or
      colonocytes, or red blood cells) and TNBS, in the presence or absence of NADPH,
      produced radical adducts characteristic of superoxide and hydroxyl radicals. Our
      EPR data showing generation of TNBS nitro and superoxide radical anions
      demonstrate that one-electron reduction of TNBS may be an initial step in the
      cascade of the in vivo inflammatory events in TNBS-induced colitis.

PMID- 9271253
TI  - Selective 'in synthesis' labelling of peptides by fluorochromes.
AB  - A new method is described for producing fluorescently-tagged peptides containing
      specific internal derivatives of lysyl residues. The technique employs the base
      labile Boc-Lys(Fmoc)-COOH derivative with base-catalyzed removal of the Fmoc
      protecting group during peptide synthesis and subsequent fluorescent
      derivatization of the deprotected epsilon-amino group of lysine. By this
      technique, other lysine residues and the alpha-amino group of the fragment remain
      unmodified, which could have some value in studies where it might be required to
      tag a single individual lysine residue within the peptide, but not the amino
      terminus. In spite of the fact that poly-substituted peptides are badly soluble
      and might seldom find a practical application, this technique also allows the
      introduction of different fluorochromes at different lysyl residues within the
      peptide, thus obtaining double fluorescence. The method, fast and easy, requires
      a limited number of manual operations during the automatic synthesis of peptides.
      Although peptide synthesizers provided with an oscillating glass reactor are more
      suitable for the manual interventions described, this technique might be also
      adapted to the newer instruments utilizing continuous-flow columns.

PMID- 9271254
TI  - Chronic ethanol administration decreases rat pancreatic GP2 content.
AB  - Postulated mechanisms of alcoholic pancreatitis include (i) zymogen granule
      fragility facilitating intracellular activation of digestive enzymes and (ii)
      ductular obstruction by protein plugs. GP2, a pancreatic glycoprotein, stabilizes
      zymogen granule membranes and is an important constituent of pancreatic protein
      plugs. Therefore, this study examined the pancreatic content and messenger RNA
      levels of GP2 after chronic ethanol administration. Rats were fed liquid diets
      with or without ethanol, for four weeks. GP2 levels in pancreatic homogenates,
      crude zymogen granules and zymogen granule membrane fractions were assessed by
      immunoblotting. Messenger RNA levels for GP2 were measured by Northern and dot
      blotting of pancreatic RNA. Pancreatic GP2 levels were lower in ethanol-fed rats
      than in controls (GP2 levels expressed as % of control: 38.75 +/- 5.8, p < 0.001
      in homogenate; 31.28 +/- 3.5, p < 0.0005 in crude zymogen granules and 22.89 +/-
      5.4, p < 0.0005 in zymogen granule membranes). Messenger RNA levels for GP2 were
      unchanged after ethanol feeding. Chronic ethanol consumption decreases GP2
      content of pancreatic homogenate and zymogen granules. This decrease could (i)
      result from an increased release into pancreatic juice thereby favouring protein
      plug formation and (ii) impair zymogen granule stability. Both these mechanisms
      could potentiate pancreatic damage.

PMID- 9271255
TI  - Molecular cloning and characterization of the epididymis-specific glutathione
      peroxidase-like protein secreted in the porcine epididymal fluid.
AB  - The epididymis-specific glutathione peroxidase was purified from the porcine
      cauda epididymal fluid in order to analyze its enzymatic activity and roles in
      the epididymis. The purified protein was found to consist of four identical 23
      kDa subunits. The complementary DNA encoding the 23 kDa subunit was cloned from
      the cDNA library of the porcine proximal caput epididymis, only where the 23 kDa
      subunit is expressed. Although the selenocysteine codon (TGA) is contained in the
      cDNA of the other cytosolic type of glutathione peroxidases, it is replaced by
      cysteine codon (TGT) in the 23 kDa subunit cDNA, similarly to the results
      previously obtained for cDNAs encoding the epididymis-specific form of the
      secreted glutathione peroxidases of mouse, rat and monkey. By the direct analysis
      of the selenium, the purified protein was proved to contain no selenium atom in
      the molecule. The activities of the purified epididymis-specific glutathione
      peroxidase toward hydrogen peroxide or organic hydroperoxides were by far lower
      than the activity of cytosolic selenium-dependent glutathione peroxidase (less
      than 0.1%). In addition, the concentration of glutathione in the porcine
      epididymal fluids was about 20 microM, which is much lower than the optimal
      concentration for the glutathione peroxidase activity of the purified protein.
      These results strongly suggest that this protein is enzymatically quiescent at
      least in the porcine epididymal fluid. An immunocytochemical study showed that
      this protein was found to bind to the acrosomal region of the epididymal sperm
      and to disappear during the acrosome reaction. Furthermore, this protein
      significantly retarded the acrosome reaction induced in vitro. The possibilities
      have been discussed that it protects sperm from the premature acrosome reaction
      and maintains sperm fertilizing ability in the epididymis.

PMID- 9271256
TI  - Glucogenesis in an insect, Manduca sexta L., estimated from the 13C isotopomer
      distribution in trehalose synthesized from [1,3-13C2]glycerol.
AB  - Glucogenesis from [3-13C]alanine and [1,3-13C2]glycerol was demonstrated in the
      insect Manduca sexta by examining the 13C enrichment of trehalose, a non-reducing
      disaccharide of glucose synthesized in the insect fat body and released into the
      blood or hemolymph. In insects maintained on a low carbohydrate diet, trehalose
      synthesized from [3-13C]alanine was selectively enriched at C1 and C6, and C2 and
      C5. The 13C-labelling pattern indicated the carboxylation of [3-13C]pyruvate,
      formed by transamination of the [3-13C]alanine followed by randomization of the
      label at the fumarate step of the tricarboxylic acid cycle and glucose synthesis
      via the gluconeogenic pathway. 13C enrichment of trehalose was absent in
      similarly maintained insect larvae administered 3-mercaptopicolinic acid, an
      inhibitor of hepatic phosphoenolpyruvate carboxykinase. Insects on the low
      carbohydrate diet also synthesized trehalose from [1,3-13C2]glycerol. 13C
      multiplets were observed in trehalose C3 and C4 demonstrating the synthesis of
      three 13C enriched glucose isotopomers from the 13C-labelled glycerol. The
      relative contributions of 13C-labelled glycerol and unlabelled 3 carbon
      substrates to the synthesis of the 13C enriched trehalose isotopomers were
      determined from the multiplet structure at C3, and calculation of minimal rates
      of glucogenesis were based on the 13C enrichment of C4. The C4/C3 13C enrichment
      ratio in trehalose synthesized from [1,3-13C2]glycerol was close to unity, and
      total glucogenesis was calculated after estimation of the expected contribution
      of unlabelled trehalose synthesis from 3 carbon substrates by comparison of the
      ratio of unlabelled and labelled contributions to the 13C enriched trehalose
      isotopomers with the 13C enrichment of [1,3-13C2]glycerol-3-phosphate. The
      estimated total rates of glucogenesis varied from 0.33 to 2.80 micromol glucose/g
      fresh weight/h. The blood sugar level of M. sexta was also highly variable.
      Although the potential importance of glucogenesis from 3 carbon substrates to the
      maintenance of blood sugar was not established by the present investigation,
      insects maintained on the low carbohydrate diet had similar blood trehalose
      levels to those previously reported by others for insects maintained on a natural
      food.

PMID- 9271257
TI  - Planar lipid bilayers on solid supports from liposomes--factors of importance for
      kinetics and stability.
AB  - One method to create planar lipid bilayers on solid substrates involves the
      transfer of lipids from liposomes to the support. We have varied the composition
      of liposomes systematically using factorial experimental designs and analyzed the
      adsorption behaviour of lipids from these liposomes onto solid supports. The
      hydrophilic supports were either used plain or modified with a monolayer of a
      lipid mixture, exposing hydrophobic groups. The monolayer-covered supports were
      used to identify factors important for adhesion and stability. Lipid adsorption
      kinetics was primarily studied on plain silicon supports in an ellipsometric cell
      or on a silicon nitride surface in a resonant mirror system (IAsys), using the
      systematic approach. Saturated phospholipids were essential for the required
      stability. Mixtures of dipalmitoylphosphatidylcholine,
      dipalmitoylphosphatidylglycerol, dipalmitoylphosphatidylethanolamine and
      cholesterol in combination with proteins were investigated in further detail as
      regards kinetics. The propensity to form a supported planar bilayer could be
      manipulated by the presence of calcium ions.

PMID- 9271258
TI  - A membrane protein primarily associated with the lysosomal compartment.
AB  - A monoclonal antibody designated MBR 39 has been generated against a membrane
      associated protein found selectively on lysosomes. MBR 39 reacts with the
      cytosolic face of the lysosome and was used to develop an organelle binding assay
      which reacted with high density organelles characteristic of lysosomes. These
      organelles contained lysosomal enzyme markers which included the integral
      membrane protein acetyl-CoA:alpha-glucosaminide N-acetyltransferase and the
      soluble lysosomal enzyme markers acid phosphatase (mature form), beta
      hexosaminidase, arylsulfatase, and alpha-L-iduronidase. Under conditions which
      disrupt lysosomes the release of the latter soluble lysosomal enzymes was
      demonstrated from MBR 39 bound organelles. Immunoblots of MBR 39 with purified
      fibroblast lysosomal membrane, demonstrated reactivity with polypeptides of
      molecular mass 63 kDa (major species) and 73 kDa (minor species).

PMID- 9271259
TI  - The interaction of abietic acid with phospholipid membranes.
AB  - Abietic acid is a major component of the oleoresin synthesized by many conifers
      and constitutes a major class of environmental toxic compounds with potential
      health hazard to animal, including human, and plant life. Being an amphipathic
      molecule, the study of the influence of abietic acid on the structure of
      membranes would be important to get insight into the mechanism of toxic action of
      the molecule. The interaction of abietic acid with model membranes of
      dipalmitoylphosphatidylcholine (DPPC) and dielaidoylphosphatidylethanolamine
      (DEPE) has been studied by differential scanning calorimetry and 31P-nuclear
      magnetic resonance spectroscopy. It has been found that abietic acid greatly
      affects the phase transition of DPPC, shifting the transition temperature to
      lower values, giving rise to the appearance of two peaks in the thermogram and to
      the presence of fluid immiscible phases. In a similar way, the phase transition
      of DEPE, in the presence of abietic acid, was shifted to lower temperatures, and
      two peaks appeared in the thermograms. The temperature of the lamellar to
      hexagonal H(II) phase transition was also decreased by the presence of abietic
      acid, but phase immiscibilities were not detected. The possible implications of
      these effects on the action of abietic acid on biological membranes are
      discussed.

PMID- 9271260
TI  - Immunogenicity and pharmacokinetic attributes of poly(ethylene glycol)-grafted
      immunoliposomes.
AB  - Immunoliposomes composed of hydrogenated soy phosphatidylcholine, cholesterol,
      methoxypoly(ethylene glycol)-distearoyl phosphatidylethanolamine (mPEG-DSPE), and
      hydrazide-PEG-DSPE (mole ratio, 57:38:3.3:1.7) linked to periodate-oxidized
      chimerized mouse IgG (C225, anti-human epidermal growth factor receptor) were
      prepared by an optimized aggregation-free procedure. The antigen-binding activity
      of the immunoliposomes was well preserved. When injected intravenously into naive
      rats, the immunoliposomes (approximately 18 IgG per 100 nm liposome) exhibited
      long circulation times (MRT = 8.5 h, Cl = 0.2 ml/h). Subsequent injections of the
      immunoliposomes into the same animals resulted in rapid clearance (MRT < or = 0.7
      h, Cl > or = 7 ml/h), which was accompanied by a significant increase in anti
      C225 specific titers. Upon repeated injection or coinjection with the parent
      liposomes free C225 consistently exhibited prolonged circulation without any
      increase in C225-specific antisera, but was cleared quickly when administered
      into animals that had been pretreated with the immunoliposomes. Screening of the
      immunoliposome induced antisera against human polyclonal IgG and C225-derived
      Fab' fragment revealed that the immune response was specifically triggered by the
      constant human region of C225. These results demonstrate that the preparations of
      PEG-grafted immunoliposomes are more immunogenic than the free IgG component,
      which is of profound importance to the antibody-mediated liposomal drug delivery
      effort.

PMID- 9271261
TI  - Isolation and characterization of the mitochondrial channel, VDAC, from the
      insect Heliothis virescens.
AB  - A 31 kDa voltage-dependent anion-selective channel (VDAC) protein was purified
      from the insect Heliothis virescens (tobacco budworm, denoted TBW) using an
      alkali extraction and filtration procedure and was characterized by SDS-PAGE,
      amino acid sequencing, biophysical properties and immunocytochemistry. The N
      terminal sequence has highest identity with VDACs from mammals (50-66%) followed
      by plants (34-41%) and lower eukaryotes (30-34%). Reconstitution in planar
      phospholipid membranes yielded properties typical of VDACs from other organisms
      including a single-channel conductance of 4.1 nS (in 1 M KCl), closure in
      response to positive and negative transmembrane voltage, and a reversal potential
      of 11.8 mV indicating anion selectivity in the open state. A polyclonal antiserum
      (R19) raised against gel-purified 31 kDa protein specifically labelled
      mitochondria and mitochondrial outer membranes in TBW flight muscle by light and
      electron microscope immunocytochemistry.

PMID- 9271262
TI  - Cloning and molecular characterization of a voltage-dependent anion-selective
      channel (VDAC) from Drosophila melanogaster.
AB  - A full length voltage-dependent anion-selective channel (VDAC) cDNA was cloned
      from Drosophila melanogaster by expression library screening using an antibody
      against an insect VDAC protein. The cDNA clone (denoted DmVDAC) is 1082 base
      pairs (bp) in length and contains an open reading frame (bp 62-907) encoding a
      282 amino acid protein which has a predicted molecular mass of 30550 Da, a
      predicted pI of 6.98 and no cysteines. Hydrophobicity analysis suggests 15 or 16
      membrane-spanning domains. The DmVDAC amino acid sequence has variable homology
      with VDACs from other species ranging from 62% identity with a human VDAC to 23%
      identity with a Dictyostelium discoideum VDAC. DmVDAC has 92% identity with the
      38 conserved residues in a VDAC consensus sequence. DmVDAC was expressed in VDAC
      null yeast but failed to rescue viability. DmVDAC has 88% identity at the amino
      acid level and 99% identity at the nucleic acid level with a recently reported D.
      melanogaster VDAC sequence (A. Messina et al., FEBS Lett. 384 (1996) 9-13).
      Homology analyses with the Messina and other VDAC sequences indicate that the
      amino acid differences are due to minor errors in the Messina sequence. Southern
      blots and chromosomal in situ hybridizations suggest a single VDAC gene occurs in
      the fly with a locus at 32B on the left arm of the second chromosome.

PMID- 9271263
TI  - Characterization of CCK receptors in stomach smooth muscle: evidence for two
      subtypes.
AB  - Cholecystokinin (CCK) and related peptides such as gastrin are important
      regulators of gastric smooth muscle contraction. Several studies have shown that
      these effects of CCK and gastrin are mediated by CCK(B) receptors. However,
      recent studies suggest the expression of an additional CCK receptor subtype
      distinct from CCK(B) receptors in this tissue. This study was designed to
      distinguish between CCK(A) and CCK(B) receptors on guinea-pig stomach smooth
      muscle cells and to evaluate these cells for additional receptor subtypes. We
      cloned these receptors by hybridization screening of a guinea-pig smooth muscle
      cDNA library using 32P random primed labeled cDNA probes from the recently cloned
      rat CCK(A) and CCK(B) receptor coding regions. In addition to clones representing
      the CCK(B) subtype, clones of CCK(A) receptor subtype, but no additional CCK
      receptor subtypes, could be identified. All isolated clones displayed highly
      homologous nucleotide sequences in comparison to previously characterized CCK(A)
      and CCK(B) receptors from different species. The results of cDNA hybridization at
      different levels of stringency and Southern blot analysis using guinea-pig
      genomic DNA suggest that it is unlikely that additional CCK receptors despite
      CCK(A) and CCK(B) receptors exist in stomach smooth muscle.

PMID- 9271264
TI  - A biotinylated perfringolysin O derivative: a new probe for detection of cell
      surface cholesterol.
AB  - theta-Toxin is a cholesterol-binding, pore-forming cytolysin of Clostridium
      perfringens. To detect cell surface cholesterol, we prepared a theta-toxin
      derivative, BC theta by biotinylation of a protease-nicked theta-toxin, which has
      the same binding affinity for cholesterol as theta-toxin without cytolytic
      activity. Human erythrocytes, V79 cells and human umbilical vein endothelial
      cells (HUVEC), were stained with BC theta coupled with FITC-avidin, and then the
      cells were analyzed by either flow cytometry or laser confocal microscopy. The
      fluorescence intensity increased in both intact and briefly fixed cells when
      treated with BC theta. BC theta-treated V79 cells were stained by neither trypan
      blue nor propidium iodide, indicating that BC stained just the outer surface of
      the plasma membrane of vital cells. Treatment of the cells with digitonin, a
      cholesterol-sequestering reagent, decreased the fluorescence intensity to the
      background level, indicating that BC theta staining is specific for cholesterol.
      The fluorescence intensity of erythrocytes pre-permeabilized with a small amount
      of theta-toxin increased more than ten-fold, suggesting higher cholesterol
      contents in the inner layer of the plasma membrane. When cells were cultured with
      cholesterol-depleted medium, the fluorescence intensity stained by BC theta
      decreased remarkably in V79 cells, but did not change in HUVEC. This indicates
      that cell surface cholesterol may be provided in different ways with these two
      cell lines. These results suggest that BC theta can be a useful probe for
      visualizing cell surface cholesterol and for evaluating the effects of cellular
      events on the topology and distribution of cholesterol.

PMID- 9271265
TI  - The anion transporter and a 28 kDa protein are selectively photolabeled by p
      azidobenzylphlorizin under conditions that alter RBC morphology, flexibility, and
      volume.
AB  - Tritiated p-azidobenzylphlorizin (p-AzBPhz) was photoactivated in the presence of
      red blood cells under conditions previously found to alter morphology,
      flexibility and volume. When less than 0.25 million molecules were added per
      cell, only a 28 kDa peptide was photolabeled: at 1-2 million molecules added,
      band 3 also incorporated significant radioactivity. When using leaky ghosts,
      other proteins became labeled, including those limited to the cytoplasm. Protein
      N-deglycosylation caused a shift of radiolabeled band 3 to higher Rf values on
      SDS-PAGE gels but not for the 28 kDa band; the latter was, however, susceptible
      to enzymatic digestion by NANase (N-acetylneuraminidase) III but not by NANase
      II. Inhibition of photoincorporation into both receptors by unlabeled p-AzBPhz
      was dose-dependent. Mercuric chloride and p-CMBS selectively blocked 28 kDa
      peptide labeling. DIDS partially blocked at band 3; after 15% inhibition, greater
      DIDS concentrations caused increased incorporation into the 28 kDa peptide. These
      results, and a temperature-dependent labeling pattern, suggest that: (i) cellular
      changes occur when p-AzBPhz binds to the exofacial sides of the anion transporter
      and 28 kDa peptide; (ii) these proteins may be physically associated in the
      native membrane; (iii) they mediate ligand-induced changes in morphology,
      flexibility, and volume.

PMID- 9271266
TI  - Radiation-inactivation analysis of the oligomeric structure of the renal sodium/D
      glucose symporter.
AB  - The radiation-inactivation size (RIS) of the rat renal brush-border membrane
      sodium/D-glucose cotransporter was estimated from the loss of transport activity
      in irradiated membrane vesicles. The RIS depended on the electrochemical
      conditions present when measuring transport activity. A RIS of 294 +/- 40 kDa was
      obtained when transport was measured in the presence of a sodium electrochemical
      gradient. Under sodium equilibrium conditions, the RIS was 84 +/- 25 kDa in the
      presence of a glucose gradient, and 92 +/- 20 kDa in its absence. In the absence
      of a sodium gradient, but in the presence of an electrical potential gradient,
      the RIS increased to 225 +/- 49 kDa. The 294 kDa result supports earlier
      suggestions that the Na+ gradient-dependent glucose transport activity is
      mediated by a tetramer. Individual monomers appear, however, to carry out glucose
      transport under equilibrium exchange conditions or when a glucose gradient serves
      as the only driving force. The electrical potential gradient-driven glucose
      transport RIS appears to involve three functional subunits.

PMID- 9271267
TI  - A large conductance, Ca2+-activated K+ channel in a human lung epithelial cell
      line (A549).
AB  - A large conductance, Ca2+-activated K+ channel in a human lung epithelial cell
      line (A549) was identified using the single channel patch clamp technique.
      Channel conductance was 242 +/- 33 pS (n = 67) in symmetrical KCl (140 mM). The
      channel was activated by membrane depolarization and increased cytosolic Ca2+.
      High selectivity was observed for K+ over Rb+(0.49) > Cs+(0.14) > Na+(0.09). Open
      probability was significantly decreased by Ba2+ (5 mM) and quinidine (5 mM) to
      either surface, but TEA (5 mM) was only effective when added to the external
      surface. All effects were reversible. Increasing cytosolic Ca2+ concentration
      from 10(-7) to 10(-6) M caused an increase in open probability from near zero to
      fully activated. ATP decreased open probability at approximately 2 mM, but the
      effect was variable. The channel was almost always observed together with a
      smaller conductance channel, although they could both be seen individually. We
      conclude that A549 cells contain large conductance Ca2+-activated K+ channels
      which could explain a major fraction of the K+ conductance in human alveolar
      epithelial membranes.

PMID- 9271268
TI  - Lipogastrins as potent inhibitors of viral fusion.
AB  - The rate and extent of membrane fusion is markedly sensitive to membrane
      interfacial properties. Lipopeptides with hydrophilic peptide moieties will
      insert into membranes, leaving the peptide portion at the membrane-water
      interface. In this work, we have used a lipopeptide composed of the peptide
      [Nle15]-gastrin-(2-17)-amide covalently linked to 1,2-diacyl-3-mercaptoglycerol
      N(alpha)-maleoyl-beta-alanine to give DM-gastrin or DP-gastrin having 14 or 16
      carbon atom acyl chains, respectively. The fluorescence emission from the two Trp
      residues of these lipopeptides exhibited little or no blue shift upon addition of
      liposomes of egg-phosphatidylethanolamine containing 5 mol% G(D1a). Iodide
      quenching of DP-gastrin fluorescence was also independent of lipid. These results
      indicate that the peptide moiety is exposed to the aqueous environment even
      though the lipopeptide is firmly anchored to the membrane. Both DM and DP-gastrin
      markedly raise the bilayer to hexagonal phase transition temperature of
      dipalmitoleoyl phosphatidylethanolamine. However, DM-E5 lowers this phase
      transition temperature. These lipopeptides have effects on the overall fusion of
      Sendai virus to liposomes in accord with their opposite effects on lipid
      curvature. The lipogastrins are potent inhibitors of viral fusion, while DM-E5
      slightly promotes this process. Truncated forms of DM-gastrin are also inhibitory
      to viral fusion, but are less inhibitory than the full lipopeptide. Analysis of
      the fusion kinetics shows that DP-gastrin causes a reduction in the final extent
      of fusion and a marked lowering of the fusion rate constant. Binding of Sendai
      virus to the ganglioside receptor-containing liposomes was not affected.
      Consideration of the various contributions to the mechanism of inhibition of
      viral fusion suggests that effects of lipogastrin on membrane intrinsic monolayer
      curvature is of primary importance.

PMID- 9271269
TI  - Effect of lipid structure on the dipole potential of phosphatidylcholine
      bilayers.
AB  - A fluorescent ratio method utilizing styrylpyridinium dyes has recently been
      suggested for the measurement of the membrane dipole potential. Up to now only
      qualititative measurements have been possible. Here the fluorescence excitation
      ratio of the dye di-8-ANEPPS has been measured in lipid vesicles composed of a
      range of saturated and unsaturated phosphatidylcholines. It has been found that
      the fluorescence ratio is inversely proportional to the surface area occupied by
      the lipid in its fully hydrated state. This finding allows, by extra- and
      interpolation, the packing density to be estimated of phosphatidylcholines for
      which X-ray crystallographic data are not yet available. Comparison of the
      fluorescence data with literature data of the dipole potential from electrical
      measurements on monolayers and bilayers allows a calibration curve to be
      constructed, so that a quantitative determination of the dipole potential using
      di-8-ANEPPS is possible. It has been found that the value of the dipole potential
      decreases with increasing unsaturation and, in the case of unsaturated lipids,
      with increasing length of the hydrocarbon chains. This effect can be explained by
      the effects of chain packing on the spacing between the headgroups. In addition
      to the effects of lipid structure on membrane fluidity, these measurements
      demonstrate the possibility of a direct electrical mechanism for lipid regulation
      of protein function, in particular of ion transport proteins.

PMID- 9271270
TI  - Pentoxifylline reduces venular leukocyte adherence ("reflow paradox") but not
      microvascular "no reflow" in hepatic ischemia/reperfusion.
AB  - Postischemic reperfusion injury is caused by microcirculatory disturbances,
      including both nutritive perfusion failure (no reflow) and leukocyte activation
      (reflow paradox). Recent studies brought evidence that pentoxifylline (PTX)
      reduces tissue injury, decreases enzyme release, and improves survival after
      normothermic liver ischemia/reperfusion. The mechanisms of action, however, by
      which PTX protects postischemic tissue from injury have not been elucidated yet.
      With the use of fluorescence microscopy in a rat hepatic ischemia/reperfusion
      model, we studied in vivo the action of PTX on the manifestation of postischemic
      sinusoidal perfusion failure and microvascular leukocyte adherence. Microvascular
      reperfusion after 20 min portal triad cross-clamping was characterized by the
      cessation of blood flow within individual sinusoids (no reflow) and accumulation
      of leukocytes within the hepatic microvasculature, with stasis in sinusoids and
      rolling and firm adherence in postsinusoidal venules. PTX (20 mg/kg x hr i.v.)
      significantly (P < 0.05) attenuated microvascular leukocyte accumulation (44,600
      +/- 1833 mm(-3) vs 67,684 +/- 2620 mm(-3) in saline-treated controls) and firm
      adherence of leukocytes in postsinusoidal venules (316.9 +/- 40.9 mm(-2) vs 522.9
      +/- 95.0 mm(-2)); however, PTX did not influence manifestation of individual
      sinusoidal perfusion failure. Since reperfusion-induced parenchymal cell damage
      was found reduced in treated animals, we conclude that PTX attenuates
      postischemic injury in rat liver by reduction of leukocytic/inflammatory response
      but not by prevention of nutritive perfusion failure.

PMID- 9271271
TI  - Heme oxygenase-dependent carbon monoxide production is a hepatic adaptive
      response to sepsis.
AB  - The hemodynamic effects of sepsis have been attributed in part to increased
      nitric oxide (NO) production and activation of guanylate cyclase, resulting in
      increased cGMP and relaxation of vascular smooth muscle. Heme oxygenase-1 (HO-1),
      a heat shock protein, has been shown to increase intracellular cGMP levels by
      formation of carbon monoxide (CO). We hypothesized that HO may be an important
      mediator of the hepatic response to infection. Male Swiss Webster mice underwent
      standard cecal ligation and puncture (CLP, 18 gauge 2X) or sham operation, and
      received either normal saline (NS) or Zn protoporphyrin IX (ZN PP IX), a
      competitive HO inhibitor (n = 6-8/group). Hepatic tissue samples were collected
      at 3, 6, 12, and 24 hr from separate mice. Serum was collected at 3 and 24 hr. A
      semiquantitative reverse transcriptase polymerase chain reaction method was used
      to measure HO-1 mRNA levels. Hepatic cGMP levels were measured by ELISA. Groups
      were repeated (n = 10/group) to assess mortality. Serum was collected at 3 and 24
      hr to measure serum aspartate aminotransferase (AST) levels. HO-1 mRNA expression
      increased significantly by 3 hr after CLP and with HO inhibition alone (P < 0.05
      vs sham + NS). HO-1 mRNA remained elevated through 24 hr. CLP animals with HO
      inhibition showed a significant reduction of hepatic cGMP following CLP compared
      with CLP + saline at 24 hr (P < 0.05). Mortality was significantly increased in
      the CLP + ZN PP group at 24 hr (P < 0.05 CLP NS vs CLP ZN PP). CLP caused a
      marked increase in AST activity, which was increased further with HO inhibition.
      HO-1 mRNA expression was induced by CLP. AST levels following CLP were markedly
      increased with HO inhibition. HO-1 function appeared to contribute to elevation
      of hepatic cGMP during peritonitis and may be an important hepatic adaptive
      response to infection.

PMID- 9271272
TI  - Activation of human somatostatin receptor type 2 causes inhibition of cell growth
      in transfected HEK293 but not in transfected CHO cells.
AB  - Somatostatin (SS) is known to have an antiproliferative effect on cell growth via
      somatostatin receptors (SSTR). The purpose of this study was to transfect cell
      lines with human SSTR2 and determine the subsequent effect on cell growth in
      response to SSTR agonist. Heterologous Chinese hamster ovary (CHO-K1) and human
      embryonic kidney 293 (HEK) cells were transfected with SSTR2 cDNA using
      lipofectin. Stable transformants were selected by G418 and confirmed by 125I-SS
      binding and RT-PCR. Binding studies were performed in the presence of 10(-6) to
      10(-12) M SS-14, SS-28, SS analogue RC-160, SSTR2 agonist NC-9-74, and SSTR5
      agonist DC-37-39. Cell growth was determined by counting cell numbers after 48 hr
      incubation in the presence of 10(-6) to 10(-12) M SSTR2 agonist NC-9-74. Binding
      of 125I-SS-14 to transfected CHO and transfected HEK293 cells showed that the
      cells had high affinity for SS-14, SS-28, NC-9-74, and RC-160 but low affinity
      for DC-37-39. Incubation with 10(-6) to 10(-12) M NC-9-74, showed that 1 nM to 1
      microM NC-9-74 significantly inhibited transfected HEK293 cell growth but did not
      affect growth on transfected CHO cells (n = 4 for each dose, P < 0.01). The two
      cell lines transfected with the human SSTR2 showed similar high affinity for SS
      14, SS-28, RC-160, and SSTR2 agonist but not SSTR5 agonist. The SSTR2 agonist NC
      9-74 significantly inhibited transfected HEK293 cell growth but not CHO cells.
      These data suggest that activation of SSTR2 was more efficiently coupled to the
      signal transduction pathway of antiproliferation in the transfected HEK293 cells.

PMID- 9271273
TI  - Ex vivo experiment on radiofrequency liver ablation with saline infusion through
      a screw-tip cannulated electrode.
AB  - PURPOSE: To investigate whether radiofrequency (RF) therapy with hypertonic
      saline infusion through a hollow screw-tip electrode can cause a lesion size
      suitable for liver tumor ablation. MATERIALS AND METHODS: RF tissue ablation of
      180 sites was performed by using a hollow screw-tip electrode in 40 freshly
      excised swine livers. Under both power and temperature control modes, the
      ablation effects with and without various regimes of 5% hypertonic saline (1
      ml/min) prior to and/or during the procedure were compared by measuring the size
      of lesions at dissection and confirmed by T1 and T2 weighted magnetic resonance
      (MR) imaging. RESULTS: The maximal lesion diameter of 5.5 cm was reached at 30 W
      with saline infusion 1 min prior to and during 12 min of ablation. The smaller
      sizes (P < 0.01) between 0.3 and 2.5 cm in diameter were met with noninfusion or
      preinfusion-only groups. The RF ablation lesions appeared as hyper- and
      hypointense areas on T1 and T2 MR images, respectively. CONCLUSIONS: RF ablation
      in combination with present hollow screw-tip electrode and saline infusion allows
      for necrotic development of suitable size for liver tumor ablation. Such ablated
      lesions can be visualized with MR imaging.

PMID- 9271274
TI  - Nitric oxide metabolism in wounds.
AB  - Arginine can be metabolized in wounds to nitric oxide and citrulline by nitric
      oxide synthase or to urea and ornithine by arginase. We investigated the
      expression of these arginine metabolic pathways over a 3-week period. Groups of 8
      10 male Balb/C mice underwent a dorsal skin incision and subcutaneous polyvinyl
      alcohol sponge implantation. The animals were sacrificed at various times, and
      sponges were harvested to obtain wound fluid and wound cells. Cells or whole
      sponges were incubated with L-[2,3-(3)H]arginine, with or without N(G)-L
      monomethyl-arginine (NMMA, a competitive inhibitor of nitric oxide synthase).
      Nitrite and nitrate (both stable end products of nitric oxide metabolism) and
      amino acids were measured in wound fluid and wound cell culture supernatants.
      Increasing concentrations of nitrite and nitrate were noted in wound fluid and in
      whole sponge cultures until the second week postwounding, indicating sustained
      wound nitric oxide synthesis. In wound fluid arginine levels were undetectable at
      all times, suggesting sustained utilization. Wound fluid citrulline levels showed
      an early peak and then a gradual decrease, suggesting that recycling for
      continued nitric oxide production may occur. Wound fluid ornithine levels
      increased until Day 10 and remained elevated, indicative of continued arginase
      activity. In vitro production of nitrite/nitrate and citrulline by cells and
      whole sponges was inhibitable by NMMA. Inducible nitric oxide synthase expression
      was confirmed by immunoblotting, while immunohistochemistry demonstrated that
      macrophages are a major source of wound nitric oxide. The data show that nitric
      oxide synthesis occurs for prolonged periods after injury and macrophages appear
      to be a major cellular source.

PMID- 9271275
TI  - Optical biopsy with optical coherence tomography: feasibility for surgical
      diagnostics.
AB  - BACKGROUND: Optical coherence tomography (OCT) is a recently developed compact
      technology which uses infrared light to perform cross-sectional imaging on a
      micrometer scale. Since OCT provides imaging at a resolution comparable to
      conventional histology and does not require direct contact with the tissue
      surface, a role in real-time surgical diagnostics represents a logical extension.
      In this work, we test the feasibility of OCT for surgical diagnostics by
      demonstrating imaging in tissue relevent to microsurgical intervention, a
      previously undescribed observation. MATERIALS AND METHODS: Over 50 sites on
      nervous, reproductive, and microvascular specimens from 10 patients were examined
      postmortem with OCT. After imaging, tissue was registered with microinjections of
      dye, under visible light laser guidance, followed by routine histologic
      processing to confirm the identity of microstructure. RESULTS: The 16 +/- 1
      microm resolution allowed subsurface microstructure to be identified at
      unprecedented resolution. Structures identified included fascicles of peripheral
      nerves, the internal elastic membrane of microvessels, and the granular layer of
      the cerebellum. CONCLUSIONS: The ability of OCT to provide micrometer-scale
      definition of tissue microstructure suggests a role in surgical diagnostics.
      Future in vivo investigations are merited to establish its utility for morbidity
      reduction associated with surgical intervention.

PMID- 9271276
TI  - Preventing gastroepiploic artery spasm: papaverine vs calcium channel blockade.
AB  - The gastroepiploic artery (GEA) is a highly vasoactive artery gaining wider
      acceptance as a conduit for coronary artery bypass surgery. A variety of agents
      are used to dilate the GEA prior to grafting; however, little is known about the
      duration of their effect in the immediate postoperative period. This study
      evaluated three calcium channel blockers and papaverine in preventing graft
      spasm. METHODS: Porcine GEA segments (10-12 cm in length) were connected to a
      computer-controlled perfusion system with a constant in-flow pressure and distal
      resistance to simulate bypass flow (80-100 ml/min). Norepinephrine (NE; 10(-9) to
      10(-5) M) was given in incremental doses at baseline before the vasodilator,
      immediately after (0 hr), and again at 2 hr after the vasodilator. Changes in
      flow and ED50 were recorded. Group INT (N = 25) received papaverine (PAP),
      diltiazem, nifedipine (NFP), or verapamil (VPL) intraluminally, while group EXT
      (N = 25) received the same dilators externally. RESULTS: All arteries showed dose
      dependent vasoconstriction to NE prior to treatment. Immediately after receiving
      the vasodilator, arteries in both groups (INT and EXT) showed initial protection
      against NE-induced spasm with the exception of arteries receiving NFD externally.
      However, at 2 hr, for group INT, only VPL and NFD prevented NE-induced graft
      spasm (VPL: 40.4 +/- 6.8 ml/min vs 17.9 +/- 3.3 ml/min and NFD: 27.0 +/- 6.5
      ml/min vs 13.1 +/- 0.9 ml/min, P < 0.02). In group EXT, after 2 hr, only VPL- and
      PAP-treated grafts showed resistance to NE-induced vasospasm (VPL: 35.6 +/- 7.3
      ml/min vs 15.0 +/- 6.9 ml/min and PAP: 47.4 +/- 15.1 ml/min vs 8.0 +/- 2.0
      ml/min, P < 0.001). CONCLUSIONS: Papaverine, a lipophilic vasodilator, when given
      externally on the perivascular fat of the GEA, prevented graft spasm for up to 2
      hr. In contrast, intraluminally applied papaverine did not show graft protection
      against NE-induced spasm. Nifedipine prevented NE-induced spasm only when given
      intraluminally. Verapamil proved to be the most potent and versatile vasodilator
      with effective graft protection of up to 2 hr whether applied externally or
      internally and was the preferred agent for protecting against GEA spasm.

PMID- 9271277
TI  - Influence of luminal hepatocyte growth factor on small intestine mucosa in vivo.
AB  - In 1984, a growth factor was identified that stimulated hepatocyte DNA synthesis.
      This growth factor, referred to as hepatocyte growth factor (HGF), has been shown
      to enhance growth of intestinal epithelial cells in vitro. Recently, we reported
      that HGF can increase absorption and intestinal mass when given systemically in
      an in vivo model. This study was designed to examine if luminally administrated
      HGF can stimulate intestinal epithelial cell mass and function. Twenty-five young
      adult Sprague-Dawley rats had catheters inserted into the small intestine and
      connected to subcutaneously placed osmotic minipumps. The rats were divided into
      five groups (n = 5 for each group) based on the contents in the osmotic pump:
      group 1 received normal saline (control); groups 2, 3, 4, and 5 received HGF in
      increasing doses of 30, 75, 150, and 300 microg/kg/day, respectively. Following a
      14-day infusion, [14C]galactose and [14C]glycine absorption was measured in 10-cm
      segments of mid-small intestine using an in vivo closed-recirculation technique.
      Mucosal DNA content and protein content of the same small bowel segment were
      determined for each group. HGF significantly increased galactose absorption at
      doses of 75 (P < 0.01) and 150 (P < 0.05) microg/kg/day and glycine absorption at
      doses of 30 (P < 0.05) and 75 (P < 0.01) microg/kg/day. HGF significantly
      increased DNA content (P < 0.01) at each dose and protein content when given at
      30 (P < 0.01) and 75 (P < 0.01) microg/kg/ day. These data demonstrate that
      luminal administration of HGF can increase intestinal epithelial cell mass and
      function in vivo. HGF may be clinically useful in patients with inadequate
      intestinal function.

PMID- 9271278
TI  - Fish oil-supplemented feeding does not attenuate warm liver ischemia and
      reperfusion injury in the rat.
AB  - Liver ischemia and reperfusion injury is mediated by oxygen free radicals,
      cytokines, and prostanoids produced by Kupffer cells and infiltrating
      neutrophils. Fish oil-supplemented diets alter membrane phospholipid composition
      and modify prostanoids and cytokine production in response to ischemia and
      reperfusion. This study tested the hypothesis that a fish oil-supplemented diet
      would attenuate warm liver ischemia and reperfusion injury in the rat. Male
      Sprague-Dawley rats were fed Vital HN supplemented with either fish oil (FO) or
      corn oil (CO) by the continuous duodenal infusion for 5 days. Total dietary fat
      (26% of total calories), caloric intake (70 cal/day), and volume (60 ml/day) were
      identical between two groups. Plasma eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) levels increased significantly in rats fed fish oil (0
      to 16.3% for EPA and 2 to 12% for DHA). Liver histology was similar in both
      groups before ischemia. On Day 6, rats were subjected to 60 min of reversible
      hepatic ischemia. Plasma TNF levels, 1 and 24 hr after reperfusion, were not
      different between FO and CO rats. Liver injury assessed by bile flow, histology,
      plasma ALT, and bile glutathione efflux did not differ between groups. We
      conclude that our fish oil-supplemented enteral diet does not attenuate warm
      liver ischemia and reperfusion injury in rats.

PMID- 9271279
TI  - Intestinal formation of hypoxanthine and uric acid during endotoxemia.
AB  - The objective of this study was to examine the intestinal metabolism of high
      energy purine compounds as sensitive indicators of tissue ischemia during
      endotoxemia. Arterial (art) and portal venous (PV) concentrations as well as the
      intestinal net concentration changes of adenosine (ADO), hypoxanthine (Hypo), and
      uric acid (UA) were measured at baseline and after 60 and 120 min in rats that
      were subjected to a 1-hr continuous infusion of endotoxin (1.5 mg/kg; group E),
      and in control animals (group C). Furthermore, the arterial (SaO2) and portal
      venous oxygen saturation (S(PV)O2) was determined at the same time points.
      Animals in both groups remained normotensive throughout the study period and no
      differences in mean arterial blood pressure were observed. In both groups,
      adenosine concentrations remained constant throughout the study and no changes in
      the net concentration difference (NCD) of adenosine between arterial and portal
      venous blood were observed [ADO(NCD); baseline: group E, -23 +/- 46 nmole/L;
      group C, 17 +/- 84 nmole/L; 120 min: group E, 14 +/- 38 nmole/L; group C, 5 +/-
      40 nmole/L]. In contrast to control animals, hypoxanthine and uric acid
      concentrations increased in arterial and portal venous blood in endotoxemic rats
      after 120 min. This was accompanied with an increase in the intestinal net
      concentration differences of both hypoxanthine and uric acid, indicating the gut
      as the predominant source of these two compounds during endotoxemia [Hypo(NCD);
      baseline: group E, -36 +/- 53 nmole/L; group C, -53 +/- 185 nmole/L; 120 min:
      group E, 538 +/- 211 nmole/L; group C, 99 +/- 100 nmole/L] [UA(NCD); baseline:
      group E, 2.04 +/- 1.62 micromole/L; group C, -0.04 +/- 1.11 micromole/L; 120 min:
      group E, 9.58 +/- 3.04 micromole/L; group C, 0.35 +/- 1.34 micromole/L].
      Furthermore, in endotoxemic rats the portal venous oxygen saturation decreased
      despite unaltered arterial oxygen saturation [SaO2; baseline: group E, 95.2 +/-
      0.9%; group C, 94.2 +/- 0.9%; 120 min: group E, 95.4 +/- 0.7%; group C, 96.4 +/-
      0.9%] [S(PV)O2; baseline: group E, 86.2 +/- 3.1%; group C, 85.7 +/- 1.4%; 120
      min: group E, 69.1 +/- 4.5%; group C, 82.3 +/- 1.9%]. These results indicate the
      presence of tissue ischemia in the intestinal tract during early, normotensive
      endotoxemia. Furthermore, because of the direct toxic damage mediated by oxygen
      radicals that are generated during the production of uric acid, intestinal
      mucosal injury observed during endotoxemia may be related to an enhancement of
      the ATP-degradation pathway.

PMID- 9271280
TI  - Hepatic inflow occlusion increases the efficacy of interstitial laser-induced
      thermotherapy in rat.
AB  - Interstitial laser-induced thermotherapy (ILT) destroys tumors thermally. ILT was
      performed for treatment of liver tumors in rats to investigate the effect of
      hepatic inflow occlusion on temperature distribution and lesion size. Tumors were
      irradiated for 20 min with near-infrared light from a neodymium:yttrium-aluminum
      garnet (Nd:YAG) laser. The laser light at a power of 1.5 W was delivered through
      a plane-cut optical fiber, the tip of which was placed in the tumor. Rats in
      group I received ILT without interruption of hepatic blood flow. Those in group
      II received ILT during hepatic inflow occlusion. Liver temperatures were measured
      during treatment. After 3 days the animals were sacrificed and the size of the
      lesions was measured. Occlusion of the hepatic inflow during ILT increased the
      maximum lesion diameter, as measured at the liver surface, by 47%. Linear
      interpolation between the temperatures measured at 6 and 12 mm distance from the
      fiber tip revealed that the temperature at the necrotic border just before the
      end of treatment was approximately 45 degrees C in both the occluded and
      nonoccluded groups, indicating that the hepatic inflow occlusion caused no
      increase in tissue thermal sensitivity. This study shows that occlusion of the
      hepatic inflow during interstitial laser-induced thermotherapy causes a
      significant increase in lesion size, which could have implications for the
      treatment of hepatic tumors.

PMID- 9271281
TI  - Fate of gelatin-resorcinol-formaldehyde/glutaraldeyde adhesive on femoral vessel
      morphology.
AB  - Several clinical reports have demonstrated that gelatin-resorcinol
      formaldehyde/glutaraldehyde (GRFG) glue can be useful in the repair of acute
      aortic dissection; however, the cellular and extracellular events that follow
      GRFG application, as well as the mechanisms responsible for the long-term
      strength and adhesive properties of GRFG, remain unclear. Accordingly, the
      present study examined the long-term effects of GRFG adhesive application on
      femoral vessel extracellular structure and composition. The left and right
      femoral artery and vein were sterilely exposed in adult rats, and GRFG (2 mL) was
      applied between and around one pair of vessels. An equivalent amount of sterile
      saline was applied to the contralateral vessels to serve as an intrinsic control.
      At either 1 (n = 6) or 2 (n = 6) months postoperatively, the lower extremities
      were perfusion fixed and harvested to preserve the native anatomy and
      cytoarchitecture of the femoral region. Gross examination of the specimens
      revealed no evidence of necrosis or wound breakdown. Tissue blocks (4 microm)
      were then sectioned perpendicular to the treated vessel region and subjected to
      histomorphometric analysis using computer-assisted microscopy. The perivascular
      capsule area, relative content of fibrillar collagen, and number of nucleated
      cells within the interstitial space were computed. At 1 and 2 months following
      the application of GRFG adhesive, perivascular capsular size increased by 42 and
      221%, respectively. Perivascular interstitial collagen content increased by 21%
      at 1 month and by 50% at 2 months. The nucleated cell number increased by 107% at
      1 month and by 166% at 2 months. This cellular infiltrate appeared to be of
      fibroblastic morphology. Thus, a potential contributory mechanism to the long
      term strength and adhesive capacities of GRFG adhesive may be extracellular
      remodeling and not the intrinsic properties of GRFG glue itself.

PMID- 9271282
TI  - Calcium release from intracellular stores and excitation-contraction coupling in
      intestinal smooth muscle.
AB  - Calcium release from intracellular stores plays a central role in excitation
      contraction coupling of striated and smooth muscle cells. Two main intracellular
      calcium pools have been identified in phasic smooth muscle: (1) the inositol
      1,4,5-trisphosphate-sensitive and the (2) ryanodine-sensitive calcium stores. We
      studied the contribution of the ryanodine-sensitive calcium stores to the
      excitation-contraction coupling in the intestine. The intracellular calcium
      concentration was measured in cultured intestinal smooth muscle cells using the
      fluorescent probe fura-2-AM. Isometric tension generated by the murine jejunum
      was recorded in vitro using force displacement transducers. The cytosolic calcium
      level increased significantly on cholinergic stimulation. The rise persisted in
      the absence of extracellular calcium. Depletion of ryanodine-sensitive calcium
      stores with caffeine or ryanodine blunted the response to a cholinergic agonists.
      Similarly, the ryanodine receptor channel blocker dantrolene significantly
      decreased the carbachol-induced calcium increase. We subsequently tested the
      effects of these pharmacological tools on the spontaneous and carbachol-induced
      contractions of the murine jejunum. Depletion of the ryanodine-sensitive stores
      and calcium release channel block both significantly decreased the contractile
      activity of the circular and longitudinal layer of the muscularis propria. Our
      data confirm the importance of intracellular calcium stores in excitation
      contraction coupling of intestinal smooth muscle cells. The effects of different
      pharmacological tools on the intracellular calcium signal and the contractile
      function are consistent with other observations in phasic smooth muscle. They
      suggest a significant contribution of calcium release from ryanodine-sensitive
      stores to the calcium signal that triggers contraction.

PMID- 9271283
TI  - The effect of oxygen delivery-directed resuscitation on splanchnic and hepatic
      oxygen transport after hemorrhagic shock.
AB  - BACKGROUND: Gut and hepatic dysfunction, during and after hypovolemic shock, have
      been implicated as causative mechanisms in the development of multiple system
      organ failure in the trauma patient. Current techniques of assessment of
      perfusion only detect changes in systemic oxygen transport. We designed an animal
      model that can measure changes in oxygen transport in the liver and gut during
      hypovolemic shock and resuscitation. MATERIALS AND METHODS: Animals were
      hemorrhaged to a mean arterial pressure (MAP) of 60 mm Hg and maintained at 60 mm
      Hg for 60 min. Animals were then assigned to one of three groups. Group I served
      as nontreatment controls. Group II received shed blood and saline in sufficient
      volumes to restore MAP to baseline. Group III animals were resuscitated with shed
      blood, saline, and donor blood to restore systemic oxygen delivery to the
      preshock value. RESULTS: The animals resuscitated to their baseline systemic
      oxygen delivery, Group III, had significantly higher systemic, hepatic, and
      splanchnic oxygen delivery than the remaining groups. In addition, Group III had
      higher oxygen consumption, portal flow, and hepatic artery flow than the blood
      pressure-directed group, Group II. The decrease in oxygen extraction ratio in the
      gut and liver was significantly greater in Group III than in Group II.
      CONCLUSIONS: These data show that hepatic and gut vascular beds are better
      perfused when resuscitation from hemorrhage is guided by systemic oxygen
      transport measurements compared to resuscitation guided by blood pressure.

PMID- 9271284
TI  - Daily supplementation with MaxEPA suppresses endotoxin-inducible monocytic
      procoagulation in dogs.
AB  - Fish intake has long been recognized to play an important role in human health,
      for example, in reduction of the incidence of heart disease and some cancers and
      as immunosuppressors. In this study, we examined the effect of dietary
      supplementation with fish oils (FO) on monocytic procoagulant activity (PCA) in
      dogs. Six mongrel dogs were fed daily chow containing FO concentrate (MaxEPA, 0.5
      g/kg body wt/day) for 8 weeks. Blood samples were drawn during a 20-week
      experimental period [i.e., before, during (weekly), and after (biweekly) MaxEPA
      supplementation] to measure monocytic PCA, PCA activation induced by endotoxin
      [lipopolysaccharide (LPS)], and plasma levels of total cholesterol, triglyceride,
      and fibrinogen (FBG). PCA was generally stimulated drastically by approximately
      19-fold on incubation of whole blood with LPS (1 microg/ml) in vitro for 2 hr.
      The basal PCA remained essentially unchanged over the entire experimental period
      irrespective of MaxEPA supplementation; however, LPS-induced PCA activation was
      reduced by 50% (P < 0.05) 3 weeks after MaxEPA was introduced. This inhibition
      remained significant up to Week 10 and reached 75% at Week 12. Thereafter, PCA
      activation gradually returned to the level before supplementation. The plasma
      levels of total cholesterol, triglyceride, and fibrinogen were determined to be
      178.8 +/- 6.0, 46.7 +/- 3.9, and 61.3 +/- 5.5 mg/dl, respectively. These plasma
      contents were neither correlated with LPS-induced PCA activation nor affected
      significantly by MaxEPA supplementation. Following a similar protocol, we also
      showed that MaxEPA supplementation resulted in a profound depression (-80%) of
      LPS-induced PCA activation in a rabbit, and PCA activation was eventually
      restored after removal of MaxEPA from the diet. Our results suggest a beneficial
      potential of MaxEPA supplementation in the management of atherothrombotic
      diseases in response to LPS infection.

PMID- 9271285
TI  - Frailty and ageing.

PMID- 9271286
TI  - Evaluation of a protocol to select patients of all ages for cardioversion from
      atrial fibrillation.
AB  - OBJECTIVE: to audit the success of a decision protocol to select patients for
      cardioversion from atrial fibrillation or flutter by recording the success of
      cardioversion and the maintenance of sinus rhythm over a 2-year period. DESIGN:
      retrospective case notes review. SETTING: a teaching hospital coronary care unit
      and cardiology department. PATIENTS: 227 consecutive patients were considered for
      cardioversion from atrial fibrillation or flutter from 1989 to 1992; 128
      fulfilled the selection criteria. MAIN OUTCOME MEASURES: successful cardioversion
      and maintenance of sinus rhythm after cardioversion. RESULTS: 116 (91%) patients
      selected by application of the guidelines were successfully cardioverted. The
      probabilities of maintaining sinus rhythm at 6, 12 and 24 months were 0.92, 0.88
      and 0.73 respectively. CONCLUSION: careful selection of patients in atrial
      fibrillation identifies a group in whom cardioversion is likely to be safe and
      successful regardless of age.

PMID- 9271287
TI  - Randomized placebo-controlled trial of brisk walking in the prevention of
      postmenopausal osteoporosis.
AB  - OBJECTIVE: to evaluate the effects of brisk walking on bone mineral density in
      women who had suffered an upper limb fracture. DESIGN: randomized placebo
      controlled trial. Assessments of bone mineral density were made before and at 1
      and 2 years after intervention. Standardized and validated measures of physical
      capacity, self-rated health status and falls were used. SETTING: district general
      hospital outpatient department. SUBJECTS: 165 women drawn from local accident and
      emergency departments with a history of fracture of an upper limb in the previous
      2 years. Women were randomly allocated to intervention (self-paced brisk walking)
      or placebo (upper limb exercises) groups. INTERVENTION: both groups were seen at
      3-monthly intervals to assess progress, measure physical capacity and maintain
      enthusiasm. The brisk-walking group were instructed to progressively increase the
      amount and speed of walking in a manner that suited them. The upper limb exercise
      placebo group were asked to carry out a series of exercises designed to improve
      flexibility and fine hand movements, appropriate for a past history of upper limb
      fracture. RESULTS: drop-outs from both intervention and placebo groups were
      substantial (41%), although there were no significant differences in bone mineral
      density, physical capacity or health status between drop-outs and participants.
      At 2 years, among those completing the trial, bone mineral density at the femoral
      neck had fallen in the placebo group to a greater extent than in the brisk
      walking group [mean net difference between intervention and placebo groups 0.019
      g/cm2, 95% confidence interval (CI) -0.0026 to +0.041 g/cm2, P = 0.056]. Lumbar
      spine bone mineral density had increased to a similar extent (+0.017 g/cm2) in
      both groups. The cumulative risk of falls was higher in the brisk-walking group
      (excess risk of 15 per 100 person-years, 95% CI 1.4-29 per 100 person-years, P <
      0.05). There were no significant differences in clinical or spinal x-ray fracture
      risk or self-rated health status between intervention and placebo groups.
      CONCLUSION: the promotion of exercise through brisk-walking advice given by
      nursing staff may have a small, but clinically important, impact on bone mineral
      density but is associated with an increased risk of falls. Self-paced brisk
      walking is difficult to evaluate in randomized controlled trials because of drop
      outs, placebo group exercise, limited compliance and lack of standardization of
      the duration and intensity of walking. Further work is needed to evaluate the
      best means of safely achieving increased activity levels in different groups,
      such as older women and those at high risk of fractures.

PMID- 9271288
TI  - Circumstances and consequences of falls in independent community-dwelling older
      adults.
AB  - BACKGROUND: knowledge of the circumstances and consequences of falls in older
      adults is important for understanding the aetiology of falls as well as for
      effective clinical assessment and design of fall prevention strategies. Such
      data, however, are relatively scarce, especially in community-dwelling elders.
      METHOD: accidental falls (including their circumstances and consequences)
      occurring in 96 male and female participants between 60 and 88 years of age were
      monitored prospectively for 1 year. After the monitoring period, participants
      were divided into three groups based on fall status: non-fallers (n = 46), one
      time fallers (n = 27) and recurrent fallers (n = 23). Frequency distributions
      were created for selected circumstances and consequences of falls and the
      prevalence of these consequences were examined. RESULTS: 50 participants (52%)
      fell during the 1 year period, amassing 91 falls. Trips and slips were the most
      prevalent causes of falls, accounting for 59% of falls. Falls most often occurred
      during the afternoon and while subjects walked on level or uneven surfaces.
      Fallers most commonly attributed falls to hurrying too much. Fractures resulted
      from five of the 91 falls and eight other falls resulted in soft tissue injuries
      that required treatment by a physician. There were no differences between one
      time and recurrent fallers in the circumstances and consequences of falls.
      However, several notable differences were found between men (n = 20) and women (n
      = 30) who fell. Falls by men most often resulted from slips whereas falls by
      women most often resulted from trips. Moreover, women and men differed in the
      time of the year in which falls occurred, with men falling most often during
      winter and women during summer. CONCLUSIONS: the results of this study provide
      insight into the circumstances and consequences of falls among independent
      community-dwelling older adults and suggest some possible ways of preventing
      falls. Preventive services, however, should not solely target recurrent fallers,
      nor should the type of services necessarily differ for one-time and recurrent
      fallers.

PMID- 9271289
TI  - Hospital discharges for pneumonia in Finland between 1972 and 1993 in the
      population aged 65 years or over.
AB  - AIM: to describe the use of hospital services by Finnish adults aged 65 or over
      with pneumonia from 1972 to 1993. MATERIAL AND METHODS: the study was based on
      nation-wide hospital discharge records. Patients in hospital for over 150 days
      were excluded. The number of persons aged 65 or over was 458,156 in 1972 and
      707,341 in 1993. RESULTS: pneumonia caused 237,330 periods of hospital treatment
      and a total of 3,826,986 hospitalization days in elderly people during the 22
      year period. Annual hospital treatment periods increased from 15.5 to 23.9 per
      1000 of population aged 65 years or over within this interval. The average annual
      change in the age-adjusted rate of hospital admissions for pneumonia was 1.45%
      [95% confidence interval (CI) 1.03 to 1.87] for males and 0.83% (95% CI 0.39 to
      1.28) for females. The increase was highest in the oldest male group, those aged
      85 years or over. In 1972 the number of hospitalization days recorded was 126,690
      (277 per 1000) and in 1993 it was 242,638 (343 per 1000), implying an absolute
      increase of 91.5%. However, the average annual change in the age-adjusted rate of
      hospitalization days for pneumonia showed a decrease of 0.62% (95% CI 1.04 to
      0.19). CONCLUSION: the recorded increase in the use of hospital services by
      elderly patients with pneumonia, combined with the current increase in size of
      the elderly population, suggests that the prevention and treatment of pneumonia
      in this sector of the population will pose a challenge for the health service in
      the future.

PMID- 9271290
TI  - Why do healthy elderly people fail to comply with influenza vaccination?
AB  - OBJECTIVE: to assess motivating factors of healthy elderly people to comply with
      influenza vaccination. DESIGN: survey of healthy elderly people invited by mail
      by their general practitioner to come for influenza vaccination. Compliance and
      the personal characteristics of gender, age and medical insurance were recorded
      by the general practitioner. A postal questionnaire assessing socio-psychological
      factors was sent to all non-compliant patients and to a random sample of 30% of
      the compliant patients. SETTING: seven family practices with a total of 26,000
      patients in The Netherlands. PATIENTS: 505 healthy elderly people over 65. MAIN
      OUTCOME MEASURES: odds ratios (ORs) for non-compliance by personal
      characteristics and socio-psychological factors, adjusted by multiple logistic
      regression analysis; decisive reason whether to comply. RESULTS: non-compliance
      was 16%. Correlations between personal characteristics and non-compliance were
      low, except for age: those under 75 were less compliant than those over 75.
      Elderly people endorsing the statement about the vaccine's serious side-effects
      displayed the highest non-compliance [adjusted OR 216; 95% confidence interval
      (CI) 16.2 to 2883]; patients judging their own health to be good were also less
      compliant (adjusted OR 57.9; 95% CI 4.4 to 770). The belief of not being
      susceptible to influenza was the most frequently mentioned reason for not
      complying, while the general practitioner's mail cue was the most common reason
      for complying. CONCLUSIONS: in healthy elderly people, fear of the side-effects
      of influenza vaccination and perceived good health seem to be the main factors
      leading to non-compliance. Better and more specific information about the paucity
      of systemic side-effects should accompany the invitations.

PMID- 9271291
TI  - The effect of chronic diseases on physical function. Comparison between
      activities of daily living scales and the Physical Performance Test.
AB  - AIM: to verify the capacity of basic and instrumental activities of daily living
      (BADL and IADL) disability scales and of a performance-based test (Physical
      Performance Test; PPT) to detect the effect on the functional capacity of several
      common chronic conditions in elderly people. METHOD: a cross-sectional survey of
      the entire population aged 70 and over, living in Ospitaletto (Brescia, northern
      Italy)-549 subjects; 89.6% of the eligible population; 179 males and 370 females
      was carried out in 1992. A multi-dimensional questionnaire administered at the
      subject's home was used to collect information on demographics, presence of
      several common chronic diseases and BADL and IADL. Objective physical capacity
      was assessed using the PPT. RESULTS: only cognitive deterioration and depression
      were independently associated with disability, as detected by BADL or IADL
      scales. Cognitive deterioration, stroke, parkinsonism, heart disease and hearing
      and visual loss were independently associated with PPT. The performance at PPT
      remained statistically associated with most of the same diseases when the
      analysis was restricted to subjects with no BADL or IADL disability. CONCLUSION:
      a performance-based measure, such as PPT, may detect a functional limitation
      before it becomes measurable by traditional self-reported BADL and IADL scales.

PMID- 9271292
TI  - Baroreflex function in sedentary and endurance-trained elderly people.
AB  - OBJECTIVE: to determine the differences associated with age and endurance
      exercise training on the baroreflex function of healthy subjects. DESIGN: cross
      sectional study. SETTING: university research department. PARTICIPANTS: 26 (10
      female) sedentary, healthy, normotensive elderly subjects (mean age 67 years,
      range 62-81), eight (two female) elderly endurance-trained athletes (66 years, 62
      69) and eight (two female) young (30 years, 25-34) subjects. MEASUREMENTS:
      baroreflex sensitivity was quantified by the alpha-index, at high frequency (HF,
      0.15-0.35 Hz) and mid frequency (MF, 0.05-0.15 Hz), derived from spectral and
      cross-spectral analysis of spontaneous fluctuations in heart rate and blood
      pressure. RESULTS: resting heart rate was significantly lower in endurance
      trained athletes than sedentary elderly people (58 +/- 12 versus 68 +/- 11 min(
      1), P < 0.05) but not different to that in healthy young subjects (63 +/- 9 min[
      1]). alpha(HF) in sedentary elderly subjects (8.1 +/- 4.2 ms.mm Hg[-1]) was lower
      than both endurance-trained elderly athletes (14.8 +/- 4.8 ms.mm Hg(-1), P <
      0.05) and healthy young subjects (28.3 +/- 21.8 ms.mm Hg(-1), P < 0.05) and was
      not significantly different between endurance-trained elderly athletes and
      healthy young subjects (P = 0.10). alpha(MF) in healthy young subjects (15.4 +/-
      8.8 ms.mm Hg[-1]) was greater than in sedentary elderly subjects (6.5 +/- 3.2
      ms.mm Hg(-1), P < 0.01) and endurance-trained elderly athletes (6.9 +/- 2.0
      ms.mmHg(-1), P < 0.01), while there was no significant difference between the two
      elderly groups (P = 0.66). CONCLUSIONS: both components of the baroreflex
      measured by the alpha-index show a decrease with age. Elderly endurance-trained
      athletes have less reduction in the high, but not mid, frequency component of the
      alpha-index compared with sedentary elderly subjects. Some of the age-related
      changes in baroreflex sensitivity may be related to physical fitness and activity
      levels.

PMID- 9271293
TI  - Age-associated cognitive decline in healthy old people.
AB  - BACKGROUND: disease often confounds the identification of risk factors for age
      associated cognitive decline in elderly subjects. If the cognitive effects of
      ageing are to be distinguished from those of disease, healthy people need to be
      studied. METHODS: we examined the effects of incident disease and drug
      prescription on cognitive change in a sample of initially healthy old people in a
      longitudinal study and related these to age, education, social class and blood
      pressure. We screened general practice case notes of 10,000 patients aged 70
      years and over resident in Edinburgh to identify potentially healthy subjects. We
      visited 1467 potential subjects at home and enquired directly about health
      problems and medications, administered the Mini-Mental State Examination (MMSE)
      and National Adult Reading Test and recorded educational attainment, occupation
      and blood pressure. RESULTS: 603 subjects (237 male, 366 female), mean age 75.7
      years (range 70-88 years), reported no health problems and were taking no regular
      medications. Four years after the initial visit we determined the outcome of all
      603 subjects and retested available survivors. Psychometric tests were then
      administered to the 429 (71.1%) available survivors after a median period of 4.2
      years (69 subjects were dead, 15 were too unwell, 12 had moved away and 78 either
      refused or failed to reply). Forty-two subjects had significant sensory
      impairment or interrupted testing, 195 remained in good health, 29 reported or
      had documented disease but were on no regular medication and 163 were on regular
      medication for diseases diagnosed during the follow-up period. MMSE score
      declined by 0.3 points in the healthy group (P < 0.048). However, once a single
      outlier whose MMSE score fell from 29 to 22 was excluded, the mean decline for
      the remainder was non-significant at 0.2 points (P = 0.079). There was no
      significant difference in cognitive decline between those who had and those who
      had not started medication (P = 0.59). CONCLUSIONS: the study fails to support
      the hypothesis that cognitive decline can be attributed to age alone in healthy
      old people. If such a decline exists, we consider that it is unlikely to account
      for loss of more than 0.1 MMSE point per year.

PMID- 9271294
TI  - Cognitive impairment: a challenge for community care. A comparison of the
      domiciliary service receipt of cognitively impaired and equally dependent
      physically impaired elderly women.
AB  - OBJECTIVES: to compare the domiciliary service receipt of cognitively impaired
      and equally dependent physically impaired elderly women prior to the passing of
      the UK Community Care Act. METHODS: secondary analysis of a population survey
      conducted in 1986 in the city of Cambridge. The analysis used data on 1585 women
      aged 75 and over living in the community. The effect of type of impairment on the
      receipt of domiciliary services (meals-on-wheels, home help and community
      nursing) is measured using a multivariate model which allows for adjustment for
      dependency level and other potential confounding factors. RESULTS: the odds of an
      elderly woman getting help from any of the domiciliary services whilst not being
      significantly affected by cognitive impairment (odds ratio 0.7, 95% CI 0.5-1.2)
      are increased by physical impairment (odds ratio 1.8, 95% CI 1.2-2.5). Similar
      results were found for the home help service. The differences were exaggerated in
      the case of the community nursing service, whilst receipt of meals-on-wheels was
      similar for women of with all types of impairment. CONCLUSIONS: in the late
      1980s, cognitively impaired elderly women received less help from the domiciliary
      services than equally dependent physically frail women who lived in similar
      household circumstances. The development of specialist services appropriate to
      the needs of cognitively impaired elderly people presents a challenge to
      community care policy, especially since this group are at high risk of
      institutionalization.

PMID- 9271295
TI  - Continuing medical education in Wales: a survey of geriatricians.
AB  - OBJECTIVE: to determine what practising geriatricians in Wales do to continue
      their education; what they would prefer to do; and what their views are on study
      leave, resources and funding. DESIGN: questionnaire survey. SETTING: the
      principality of Wales. PARTICIPANTS: hospital-based, career-grade geriatricians.
      RESULTS: the overall response rate from a total of 56 questionnaires was 87%.
      More than half [26 (53%)] of the respondents stated they were able to take only
      half of their study leave entitlement of 10 days a year. Twenty-five (51%)
      considered this to be due to service commitment. Geriatricians regarded
      attendance at routine hospital meetings [47 (96%)] and specialist society
      meetings [45 (92%)], reading books and journals [49 (100%)] and discussion with
      colleagues [44 (90%)] as their preferred methods of keeping up to date. Most
      respondents [44 (90%)] said that the resources and funding required to underpin
      the system of continuing medical education (CME) should be provided by the
      employing authority. CONCLUSIONS: the many barriers to the continuing education
      of geriatricians in Wales include service commitments and funding constraints.
      Geriatricians placed great emphasis on the traditional CME methods such as
      reading books and journals, attending meetings and conferences and discussion
      with colleagues and were reluctant to use technology-based educational methods.
      The results of this study have implications for the way in which geriatricians
      fulfil CME obligations in the future and provide directions for the planners of
      CME.

PMID- 9271296
TI  - Unstable disability and the fluctuations of frailty.

PMID- 9271297
TI  - Prevalence of anticardiolipin and antinuclear antibodies in an elderly
      hospitalized population and mortality after a 6-year follow-up.

PMID- 9271298
TI  - Inappropriate acute admissions from nursing and residential homes.

PMID- 9271299
TI  - Rapid activation of PDGF-A and -B expression at sites of lung injury in asbestos
      exposed rats.
AB  - The development of interstitial pulmonary fibrosis is associated with a variety
      of inflammatory mediators, including peptide growth factors and cytokines. In the
      work presented here, we have asked whether or not platelet-derived growth factor
      (PDGF)-A and -B genes and proteins are expressed in anatomic and temporal
      patterns consistent with this factor playing a role in the disease process. Using
      an established rat model of asbestos-induced fibroproliferative lung disease, we
      demonstrate elevated levels of PDGF-A and -B mRNAs in total lung RNA immediately
      after a single 5-h exposure to approximately 1,000 fibers/ml of chrysotile
      asbestos. In situ hybridization revealed the PDGF-A and -B in RNAs primarily in
      macrophages and bronchiolar-alveolar epithelial cells at sites of initial fiber
      deposition and lung injury. There was clear evidence of PDGF-A and -B mRNAs in
      interstitial cells as well. The pattern of in situ hybridization was entirely
      consistent with the appearance (established by immunohistochemistry) of PDGF-A
      and -B proteins by 24 h post-exposure in the same cell types. Both mRNAs and
      proteins remained detectable at the fiber deposition sites for almost 2 wk post
      exposures. These findings are consistent with our previous studies showing
      increased mesenchymal cell proliferation and fibroproliferative lesions that
      progress at the sites where PDGF-A and -B are expressed. Although it is clear
      that multiple growth factors are produced simultaneously at sites of initial
      injury, we suggest that the PDGF isoforms could be playing a central role in the
      disease process based upon their potent mitogenic effects upon mesenchymal cells.

PMID- 9271300
TI  - Clara cells and Clara cell 10 kD protein (CC10).

PMID- 9271301
TI  - Perhaps airway smooth muscle dysfunction contributes to asthmatic bronchial
      hyperresponsiveness after all.

PMID- 9271302
TI  - Altered pulmonary response to hyperoxia in Clara cell secretory protein deficient
      mice.
AB  - Clara cell secretory protein (CCSP) is an abundant component of the extracellular
      lining fluid of airways. Even though the in vivo function of CCSP is unknown, in
      vitro studies support a potential role of CCSP in the control of inflammatory
      responses. CCSP-deficient mice (CCSP -/-) were generated to investigate the in
      vivo function of this protein (13). In this study, we used hyperoxia exposure as
      a model to investigate phenotypic consequences of CCSP deficiency following acute
      lung injury. The pathologic response of the mouse lung to hyperoxia, and recovery
      of the lung, include inflammatory cell infiltrate and edema. Continuous exposure
      to > 95% O2 was associated with significantly reduced survival time among CCSP -/
      mice as compared with strain-, age-, and sex-matched wild-type control mice.
      Differences in survival were associated with early onset of lung edema in CCSP -/
      mice as compared with wild-type controls. To further investigate these
      differences in response, mice were exposed to > 95% O2 for either 48 h or 68 h
      with one group receiving 68 h of hyperoxia followed by room-air recovery. Lung
      RNA was characterized for changes in the abundance of cytokine messenger RNA
      (mRNA) using a ribonuclease (RNase) protection assay. After 68 h of hyperoxia,
      interleukin-6 (IL-6), IL-1beta, and IL-3 mRNAs were 14-, 3-, and 2.5-fold higher,
      respectively, in CCSP -/- mice than in similarly exposed wild-type control mice.
      Increased expression of IL-1beta mRNA in hyperoxia-exposed CCSP -/- mice was
      localized principally within the lung parenchyma, suggesting that the effects of
      CCSP deficiency were not confined to the airway epithelium. We conclude that CCSP
      deficiency results in increased sensitivity to hyperoxia-induced lung injury as
      measured by increased mortality, early onset of lung edema, and induction of
      proinflammatory cytokine mRNAs.

PMID- 9271303
TI  - Airway responsiveness in two inbred strains of mouse disparate in IgE and IL-4
      production.
AB  - The mouse provides an excellent model for genetic studies of asthma, which is
      characterized by airway hyperexcitability and hyperreactivity. The former is a
      function of the properties of the membrane of the airway smooth muscle (ASM),
      whereas the latter is a function, albeit indirectly, of the mechanical properties
      of the muscle contractile apparatus. The very small size of the muscle has in the
      past hampered its study. We report herein that contractile properties of tracheal
      smooth muscle (TSM) can be measured in mice. We examined TSM strips from two
      inbred strains of mouse, ASW and SJL, which are high and low IgE responders,
      respectively. Force-velocity relationships were measured in four groups of mice,
      two ASW (control and sensitized)/and two SJL (control and sensitized). Muscle
      strips from sensitized SJL mice exhibited shortening velocities (V0) and maximum
      shortening capacities (deltaLmax), that were significantly greater than those of
      the other groups. However, no difference was found between the two strains in
      maximal isometric force (P0). The two strains also showed differences in their
      potential to express cytokines such as interleukin-4 (IL-4) and IL-5 in ex vivo
      splenocyte cultures, as measured by the cytokines' messenger RNA (mRNA) and
      protein expression. The SJL strain, which exhibited TSM hyperreactivity, was
      found to produce significantly greater amounts of IL-4 than the ASW strain. We
      conclude that the altered contractile properties of TSM in sensitized SJL mice
      are independent of IgE response, but linked to increased amounts of IL-4.

PMID- 9271304
TI  - Tissue factor expression in mesothelial cells: induction both in vivo and in
      vitro.
AB  - Exudative pleural effusions are characterized by a high protein content and
      frequently progress to loculation and fibrosis. To test the hypothesis that
      tissue factor (TF) plays an integral role in this process, we investigated the
      expression of TF by human mesothelial cells (HMC) both in vivo and in vitro, and
      measured the effect of serum on HMC expression of TF in vitro. In vivo TF
      expression was not detected in HMC of normal pleura, but was detected in HMC of
      pleura overlying inflamed lung. In vitro, quiescent HMC demonstrated negligible
      levels of TF expression; however, upon serum stimulation there was a marked
      induction in both TF protein level and activity, peaking at 8-9 h. In contrast,
      treating quiescent HMC with plasma resulted in a further small, but significant,
      decrease in TF expression. This serum-induced rise in TF was also reflected in TF
      mRNA levels and did not require de novo protein synthesis. These results suggest
      that induction of HMC TF expression may be important in triggering both the
      intrapleural activation of prothrombin and the deposition of fibrin
      characteristic of inflammatory effusions.

PMID- 9271305
TI  - Expression of nitric oxide synthases and GTP cyclohydrolase I in the ventilatory
      and limb muscles during endotoxemia.
AB  - Nitric oxide synthases (NOS) convert L-arginine to nitric oxide in the presence
      of tetrahydrobiopterin (BH4). Two constitutive isoforms of NOS exist in normal
      skeletal muscle fibers, however, the existence of a third, the inducible isoform
      (iNOS), has never been detected in these fibers in vivo. Therefore, we assessed
      the influence of in vivo endotoxemia on skeletal muscle expression of
      constitutive and inducible NOS isoforms and GTP cyclohydrolase I, the rate
      limiting enzyme of BH4 synthesis. Two groups of rats were infused i.p. either
      with E. coli endotoxin (20 mg/kg, LPS group) or saline (saline group). Animals
      were killed 6 h later and the ventilatory and limb muscles were quickly frozen.
      Endotoxin infusion elicited a significant rise in NOS activity of the diaphragm,
      intercostal, soleus and gastrocnemius muscles. Reverse transcription-polymerase
      chain reaction (RT-PCR) on muscle total RNA detected very low expression of iNOS
      and GTP cyclohydrolase I mRNA in the saline group, but significant upregulation
      of both enzymes was found in the ventilatory and limb muscles of the LPS group.
      Immunoblotting detected no iNOS protein in the saline group but a significant
      iNOS protein expression was found in the diaphragm, intercostal and soleus
      muscles and to a lesser extent, in the gastrocnemius of the LPS group.
      Endotoxemia was also associated with increased protein expression of constitutive
      NOS isoforms mainly in the diaphragm and to lesser extent in the intercostal,
      gastrocnemius and soleus muscles. We conclude that in vivo exposure to endotoxin
      leads to differential induction of both iNOS and GTP cyclohydrolase I in the
      ventilatory and limb muscles.

PMID- 9271306
TI  - Human endothelial cells synthesize ENA-78: relationship to IL-8 and to signaling
      of PMN adhesion.
AB  - The interaction of endothelial cells and polymorphonuclear leukocytes (PMNs,
      neutrophils) is a critical determinant of the acute inflammatory response, and
      mirrors cell-cell interactions in other biologic systems. Adhesion molecules that
      tether the two cells together, and signaling factors that bind to receptors on
      the leukocytes and mediate their spatially-localized activation, govern PMN
      responses as they adhere to and traverse stimulated endothelial cells. Here we
      show that cultured human endothelial cells express two members of the C-X-C
      family of chemokines, epithelial neutrophil activating peptide-78 (ENA-78) and
      interleukin (IL)-8, when stimulated by IL-1 or certain other agonists. ENA-78,
      previously thought to be exclusively a product of epithelium, is expressed by in
      situ endothelium in inflamed human lung and other tissues as well as by cultured
      endothelial cells. The regulation of ENA-78 and IL-8 share certain features in
      common and they have overlapping biologic activities, including the ability to
      induce PMN adhesiveness. This was demonstrated in experiments in which we found
      that ENA-78 induces inside-out signaling of beta2 integrins on the PMN surface,
      as does IL-8. Antibody blocking experiments demonstrated that ENA-78 contributes
      to the proadhesive activity for neutrophils that is released by endothelial cells
      stimulated with IL-1 for a prolonged period and that it acts in concert with IL
      8, which provides the major component of the signal for adhesion under this
      condition. We also show, however, that the temporal expression and secretion of
      ENA-78 and other characteristics of its handling by stimulated endothelial cells
      vary from the expression of IL-8, indicating that differential regulation of the
      two signaling chemokines occurs in this cell type.

PMID- 9271307
TI  - Increased expression of interleukin-16 in bronchial mucosa of subjects with
      atopic asthma.
AB  - Asthma is characterized by the presence of activated CD4+ cells in the airways.
      We hypothesized that the newly characterized cytokine interleukin (IL)-16 is
      involved in the pathogenesis of asthma through its ability to selectively induce
      CD4+ cell recruitment within the inflamed bronchial wall. We investigated the
      expression of IL-16 in bronchial biopsies obtained from subjects with mild asthma
      (n = 10), atopic nonasthmatic individuals (n = 6), and normal control subjects (n
      = 10). Cryostat sections from 4% paraformaldehyde-fixed fiberoptic bronchial
      biopsies were immunostained using a specific antibody that recognizes human IL
      16. IL-16 mRNA expression was determined by in situ hybridization. IL-16
      immunoreactivity and mRNA were demonstrated mainly in bronchial epithelial cells
      in all subjects. IL-16 immunoreactivity and IL-16 mRNA expression within the
      epithelium were significantly higher in bronchial biopsies obtained from
      asthmatic subjects as compared to both atopic nonasthmatic and normal controls (P
      < 0.001). The numbers of subepithelial IL-16 immunoreactive cells and IL-16 mRNA
      positive cells were also greater in the bronchial biopsies obtained from
      asthmatic subjects as compared to both atopic nonasthmatic and normal controls (P
      < 0.001). Epithelial expression of IL-16 immunoreactivity and mRNA correlated
      with the CD4+ cell infiltration (r2 = 0.70, P < 0.001). There were significant
      associations between epithelial and subepithelial IL-16 immunoreactivity and
      airway responsiveness to methacholine. This study demonstates that IL-16 is
      expressed in airway tissues, particularly in the epithelial cells, and that up
      regulation of its expression is a feature of allergic asthma. These results
      suggest an in vivo role for IL-16 in the pathogenesis of asthma, possibly through
      the recruitment of CD4+ cells, and support the increasing evidence for the
      participation of epithelial cells in regulating inflammatory responses.

PMID- 9271308
TI  - Acute and long-term effects of stressors on pulmonary immune functions.
AB  - To study the effects of different types or intensities of stressors on immune
      reactivity in the lungs, we studied the ex vivo production of nitric oxide (NO)
      and IL-1beta by alveolar macrophages (AM) after short exposure of rats to
      restraint stress or inescapable electric footshocks. Exposure to electric
      footshocks of various intensities resulted in an intensity-dependent decrease in
      NO production whereas the IL-1beta production by AM had increased. The secretory
      activity was similarly affected by restraint stress. When the time course of
      electric footshocks on secretory functions of AM was studied, it was found that
      the effects on NO and IL-1beta production by AM were normalized 3 days after the
      stress induction, but reappeared when cells were isolated 1 to 2 wk after stress
      exposure. Analysis of the effects of electric footshocks of various intensities
      on antibody production 10 days after the stress session and subsequent lung
      immunization with trinitrophenyl conjugated keyhole limpet hemocyanin (TNP-KLH),
      showed a footshock intensity-dependent response. Although exposure to stress
      induced an increase in plasma levels of adrenocorticotropic hormone (ACTH) and
      corticosterone (CORT), hormone levels did not differ between the various stress
      exposed groups. This suggests that the observed stress effects on pulmonary
      immune functions were not mediated by ACTH or CORT but point to a direct
      involvement of the autonomic nervous system.

PMID- 9271309
TI  - Surfactant protein A (SP-A) mediates attachment of Mycobacterium tuberculosis to
      murine alveolar macrophages.
AB  - Attachment of Mycobacterium tuberculosis organisms to alveolar macrophages (AMs)
      is an essential early event in primary pulmonary tuberculosis. Surfactant protein
      A (SP-A) is a nonimmune opsonin present in the alveolar spaces that binds
      carbohydrate residues such as mannose. It was hypothesized that SP-A attaches to
      M. tuberculosis and serves as a ligand between M. tuberculosis and AMs. [125I]SP
      A was found to bind to M. tuberculosis in a time- and [Ca2+]-dependent manner
      with a Kd of 1.9 x 10(-9) M and an apparent number of 6.3 x 10(2) SP-A binding
      sites/organism. Further, deglycosylated SP-A had minimal binding to M.
      tuberculosis, indicating that sugar moieties are important in this interaction.
      SP-A specifically binds to a 60-kD cell-wall protein from M. tuberculosis. SP-A
      mediated attachment of 51Cr-labeled M. tuberculosis organisms to AMs is dependent
      on time, SP-A concentration, and Ca2+. M. tuberculosis attachment to murine AMs
      in the absence of SP-A was 12.8 +/- 0.9%; however, in the presence of 5 microg/ml
      SP-A the attachment increased to 38.6 +/- 2.9% (P < 0.001). SP-A-mediated
      attachment was significantly decreased from 38.6 +/- 2.9% to 18.7 +/- 3.3% (P <
      0.05) in the presence of antihuman SP-A antibodies. When the attachment assay was
      repeated in the presence of alpha-methylene-D-mannosepyranosidase (mannosyl-BSA)
      and type V collagen, SP-A-mediated attachment decreased from 38.6 +/- 2.9% to
      16.6 +/- 1.5% (P < 0.001) and 19.1 +/- 1.4% (P < 0.05), respectively. Further,
      deglycosylated SP-A had only a minimal effect on M. tuberculosis attachment to
      AMs. These data indicate that SP-A can mediate M. tuberculosis attachment to AMs,
      and suggest possible underlying mechanisms for this.

PMID- 9271310
TI  - Inability of histamine to regulate TNF-alpha production by human alveolar
      macrophages.
AB  - Tumor necrosis factor alpha (TNF-alpha), a major product of alveolar macrophages
      (AM), has been implicated in many pulmonary diseases. Histamine, a mediator
      important in pulmonary inflammation, has been demonstrated to regulate the
      production of TNF-alpha by monocytes. In this study, we show that human AM and
      monocytes differ in their responses to histamine. Whereas histamine suppressed
      lipopolysaccharide (LPS)-stimulated TNF-alpha production by monocytes through a
      cAMP-dependent mechanism, it had no effect on either cAMP levels or TNF-alpha
      production by AM. In contrast, both PGE2 and IL-10 suppressed LPS-stimulated TNF
      alpha production by AM and monocytes. The lack of response of AM to histamine
      appears unique, as histamine suppressed LPS-stimulated TNF-alpha production by
      mononuclear cells isolated from sites of acute and chronic inflammation, as well
      as from noninflammatory tissues, and by macrophages differentiated in vitro. In
      the presence of the phosphodiesterase (PDE) inhibitor 3-isobutyl-1
      methylxanthine, histamine increased cAMP levels in AM. Freshly isolated monocytes
      and AM did not differ in PDE activity. However, PDE activity in AM, but not in
      monocytes, was increased 15 min after culture with histamine and may, in part, be
      responsible for the inability of histamine to suppress TNF-alpha production by
      AM. However, this increase was small and we hypothesize that additional
      mechanisms may contribute to the unresponsiveness of AM to histamine. We suggest
      that the lack of response of AM to histamine may be important in the host defense
      function of AM in the distal lung.

PMID- 9271311
TI  - Induction of cystine transport and other stress proteins by disulfiram: effects
      on glutathione levels in cultured cells.
AB  - Disulfiram (Antabuse) (DSF) has been reported to protect rats and other animals
      from the effects of hyperbaric hyperoxia at 4 to 6 ATA (atmospheres). In
      contrast, DSF and diethyldithiocarbamate (DDC), its metabolite, accelerate the
      toxic effects in rats of 100% oxygen at 1 to 2 ATA. We have examined the effects
      of DSF and DDC on glutathione (GSH) levels in bovine pulmonary artery endothelial
      cells and Chinese hamster ovary cells. Increases in intracellular GSH occurred 8
      to 24 h after addition of DSF to the culture media. These increases in
      intracellular GSH were associated with increases in the rate of uptake of cystine
      into the cells. DDC was a less effective inducer of cystine uptake and increased
      intracellular GSH levels than was DSF. At the concentrations used, neither DDC
      nor DSF caused significant decreases in intracellular superoxide dismutase
      levels. Exogenous sulfhydryl compounds including GSH and cysteine partially
      blocked the induction of cystine transport by DSF or DDC, suggesting that the
      induction might be mediated through a sulfhydryl reaction between DSF and some
      cellular components. The increases in GSH in the cultured cells were not
      significant by 4 h of exposure. In contrast, other stress proteins including heme
      oxygenase are induced by 2 to 4 h after DSF addition. In previously reported in
      vivo studies, DSF treatment protected against hyperbaric oxygen damage after as
      little as 1 to 4 h pre-exposure. This suggests that effects of DSF exposure other
      than GSH augmentation may be responsible for the protective effects seen in vivo.

PMID- 9271312
TI  - Differential regulation of human, antigen-specific Th1 and Th2 responses by the B
      7 homologues, CD80 and CD86.
AB  - A selectivity of B7.1 (CD80) for promoting Th1 responses and B7.2 (CD86) for
      promoting Th2 responses in the murine system has recently been suggested. The
      present study explores this hypothesis, using human PBMCs and antigen-specific
      Th1 and Th2 clones. Proliferative responses of peripheral blood mononuclear cells
      (PBMCs) from ragweed-allergic, tetanus toxoid-immunized individuals were
      downregulated by treatment with anti-CD86 in ragweed- and tetanus toxoid-driven
      cultures (% Inhibition = 55 +/- 4 and 61 +/- 12, respectively; P < 0.03 relative
      to untreated cultures). Gene expression in PBMCs for interleukin (IL)-4, IL-5,
      and interferon gamma (IFNgamma), assessed by reverse-transcriptase polymerase
      chain reaction, was also downregulated by treatment with anti-CD86 in both the
      ragweed- and tetanus toxoid-driven systems. Neither independent efficacy nor
      synergy with anti-CD86 was apparent with anti-CD80 treatment; two different anti
      CD80 blocking antibodies yielded identical results. Conversely, antigen-specific
      Th1 and Th2 clones were insensitive to treatment with either anti-CD80, anti
      CD86, or a combination of the two. Unaffected parameters included proliferative
      response (P < 0.14 and 0.33, respectively, for Th1 and Th2), proinflammatory
      cytokine gene expression, and cytokine protein secretion into culture
      supernatants (P < 0.44 and 0.16, respectively, for IL-4 and IFNgamma). We
      conclude that CD86 is the primary B7 signaling homologue in human PBMC responses,
      and that second signal pathways through the B7 homologues have no effect on
      phenotypically differentiated T helper cells in humans.

PMID- 9271313
TI  - Cyclosporin A and FK506 reduce interleukin-5 mRNA abundance by inhibiting gene
      transcription.
AB  - The cytokine interleukin-5 (IL-5) selectively induces the proliferation,
      differentiation, and activation of mature eosinophils. The immunosuppressive
      agents cyclosporin A (CsA) and FK506 ameliorate the influx of eosinophils seen in
      allergic conditions such as asthma. We investigated the mechanisms controlling IL
      5 messenger RNA (mRNA) expression in human T-lymphocytes in the presence of CsA
      or FK506. Fresh human peripheral blood mononuclear cells (PBMC); 7-day cultured
      PBMC, which represent a population of activated T-lymphocytes derived from PBMC;
      and the T-cell line HSB-2 were used. A novel polymerase chain reaction (PCR)
      based nuclear run-on assay was employed to investigate the rate of IL-5 gene
      transcription. IL-5 mRNA degradation was measured by quantitative reverse
      transcriptase (RT)-PCR. CsA and FK506 strongly inhibited cellular IL-5 mRNA
      expression in response to phytohemagglutinin (PHA), or to phorbol myristate
      acetate (PMA), and/or calcium ionophore. Marked inhibition was observed in PBMC,
      7-day cultured PBMC, and HSB-2 cells. Nuclear run-on assays done with either 7
      day cultured PBMC or HSB-2 cells demonstrated striking inhibition of IL-5 gene
      transcription by both CsA and FK506 at levels reflecting the degree of reduction
      of total cellular IL-5 mRNA abundance. Neither CsA or FK506 had any detectable
      effect on the stability of IL-5 mRNA. Thus, the inhibitory effect of CsA and
      FK506 on cellular IL-5 mRNA expression can be explained by inhibition of the rate
      of IL-5 gene transcription.

PMID- 9271314
TI  - Phosphatase inhibitors potentiate 4-hydroxynonenal-induced phospholipase D
      activation in vascular endothelial cells.
AB  - We have previously reported that endothelial cell phospholipase D (PLD),
      activated by 4-hydroxynonenal (4-HNE), was independent of protein kinase C
      activation. To determine whether PLD stimulation by 4-HNE is related to protein
      tyrosine phosphorylation, the effects of tyrosine kinase (Tyrk) and protein
      tyrosine phosphatase (PTPase) inhibitors on PLD activation were investigated.
      Pretreatment of bovine pulmonary artery endothelial cells (BPAEC) with Tyrk
      inhibitors, such as genistein, erbstatin, and herbimycin attenuated 4-HNE-induced
      PLD activation. Furthermore, vanadate, phenylarsine oxide, and diamide,
      inhibitors of PTPases, markedly increased the 4-HNE-induced PLD activation. The
      effects of Tyrk and PTPase inhibitors were specific towards the 4-HNE, as these
      agents had no effect on the agonist- or TPA-induced PLD activation. In addition
      to PLD activation, treatment of BPAEC with 4-HNE increased tyrosine
      phosphorylation of proteins including bands of molecular weights 40,000-60,000,
      70,000-90,000, and 110,000-130,000. The 4-HNE-mediated increase in protein
      tyrosine phosphorylation was partly inhibited by genistein (100 microM). Vanadate
      (10 microM) pretreatment also potentiated 4-HNE-induced protein tyrosine
      phosphorylation. These data suggest that 4-HNE-mediated stimulation of PLD may
      occur as a result of activation of tyrosine kinases.

PMID- 9271315
TI  - Reactive oxygen species modified thymine and poly(dT) present unique epitope for
      human anti-DNA autoantibodies.
AB  - Hydroxyl radical, one of the most potent of all reactive oxygen species has been
      implicated in many human degenerative diseases and is known to modify adenine and
      thymine in cellular DNA. In the present studies, adenine, thymine and their
      synthetic homopolymers poly(dA), poly(dT) were ROS-modified and subsequently used
      as inhibitors of native DNA binding to human anti-DNA autoantibodies. Besides
      nDNA, modified thymine and poly(dT) were effective inhibitors of DNA-anti-DNA
      antibody interaction. The relative affinity of ROS-modified poly(dT) was better
      than that of native DNA. Visual detection of modified thymine and poly(dT)
      binding to affinity purified anti-DNA IgG by an indirect band shift assay support
      competition inhibition data. The enhanced recognition of ROS-DNA by anti-DNA
      autoantibodies, as reported earlier, could be due to the ROS-induced modification
      of thymine.

PMID- 9271316
TI  - Augmentation of tumor necrosis factor-alpha-induced priming of fMet-Leu-Phe
      stimulated neutrophils by pentoxifylline.
AB  - Tumor necrosis factor-alpha (TNF) is reported to cause tissue damage via enhanced
      neutrophil (PMNL) degranulation, superoxide production and altered PMNL
      migration. We investigated the effect of pentoxifylline (PTX) on TNF-induced
      respiratory burst activity of the PMNL. Since PTX has been reported to influence
      TNF-induced PMNL functions, our studies focused on the effects of timing and
      duration of the presence of PTX on superoxide anion production by PMNL exposed to
      TNF. When PMNL are exposed to PTX prior to priming with TNF and triggering with
      fMLP, respiratory burst activity was significantly enhanced by PTX, whereas the
      stimulatory effect of TNF was completely blunted by the continuous presence of
      PTX. Since free radical-scavenging properties of PTX have only recently been
      identified and may explain inhibitory effects on TNF-induced respiratory burst
      reported in the literature, our data for the first time suggests additive priming
      actions of PTX and TNF on PMNL respiratory burst activity.

PMID- 9271317
TI  - Studies on the mechanism and specificity of the effect of the synthetic random
      copolymer GLAT on graft-versus-host disease.
AB  - Graft-versus-host disease (GVHD), which occurs when donor T-cells recognize
      multiple minor host histocompatibility antigens as non-self, presents the major
      limitation to successful allogeneic bone-marrow transplantation. The synthetic
      random copolymer of the amino acids, L-Glu, L-Lys, L-Ala and L-Tyr, termed GLAT,
      with promiscuous binding to multiple MHC class II alleles, reduces the incidence,
      onset and severity of disease in the BIO.D2 --> BALB/c model of lethal GVHD. GLAT
      inhibited the proliferative response towards host of both spleen cells from mice
      with GVHD and also of the effector T cell line established from these mice.
      Administration of GLAT for a limited period after transplantation completely
      abolished the cytotoxic activity toward host cells exerted by spleen cells from
      mice with GVHD. Whereas spleen and bone marrow cells from control mice with GVHD
      secreted IL-2 and INF-gamma when cocultured with host cells, these inflammatory
      cytokines could not be detected in supernatants of cells from GLAT treated mice.
      Moreover spleens and bone marrow cells from GLAT treated mice secreted small but
      significant amounts of IL-4 and IL-6 when cocultured with GLAT, suggesting that
      GLAT not only inhibits pro-GVHD cytokines but also causes a beneficial effect by
      inducing secretion of Th2 type cytokines. GLAT binds strongly to MHC molecules of
      host as well as donor haplotype. D-GLAT, identical to GLAT but composed of D
      amino acids is also effective in preventing GVHD. D-GLAT does not cross-react
      with L-GLAT, but still binds strongly to MHC-class II molecules. These findings
      indicate that MHC blocking is involved in the therapeutic effect of GLAT on GVHD.
      The cumulative data demonstrate that GLAT modulates the effector mechanisms
      involved in GVHD, and can be potentially used for the prevention of GVHD across
      minor histocompatibility barriers.

PMID- 9271318
TI  - The N-terminal six residues of peptide core sequences suffice for binding to HLA
      DR4 (DRB1*0405) and DR9 (DRB1*0901) molecules.
AB  - When examining anchor residues of a peptide 0405BP2 (1SPGTGAYYVLLN12) that was
      eluted from purified HLA-DR4 molecules (DRA/DRB1*0405), we found that heptamer
      peptides K7YYVLLN12 and K7YAALAN12 could bind to DR4 with the same affinity as
      0405BP2, where artificially added Lys increases the solubility of peptides, and
      7Y, 10L and 12N function as major anchor residues. In contrast, none of
      K8YVLLN12, K8AALAN12, K7YYVLL11 and K7YAALA11 had any detectable binding. Similar
      results were obtained with peptide K1WAASAAAAA9 that binds to DR9 (DRA/DRB1*0901)
      where 1W and 4S function as major anchor residues; K1WAASAA6, but not K1WAASA5 or
      K2AASAAAAA9 did bind to DR9 molecules. These data indicate that, when the most N
      terminal anchor is designated as P1 (position 1), P1-6 but not P7-9 is essential,
      for binding at least to HLA-DR4 and DR9 molecules.

PMID- 9271319
TI  - Immune responsiveness of splenocytes after chronic daily melatonin administration
      in male Syrian hamsters.
AB  - The interrelationships between the immune system and the pineal hormone,
      melatonin, have been explored recently. The present studies investigated the
      effects of daily melatonin injections on reproductive and spleen function in male
      Syrian hamsters. Testes weights and serum testosterone levels were depressed
      after 8-10 weeks of daily melatonin injections. Melatonin-treated hamsters
      exhibited increased splenic lymphoproliferative responses to a polyclonal T-cell
      mitogen (concanavalin A (Con-A)), but decreased proliferation following
      stimulation with a polyclonal B-cell mitogen (lipopolysaccharide). It appears
      that daily melatonin injections in male hamsters increase the T-cell-mediated
      immune capacity while reducing the antibody-mediated immune potential. These data
      suggest that chronic, daily melatonin alters immune system responsiveness in
      hamsters by shifting the balance of cellular and humoral reactivity.

PMID- 9271320
TI  - Massive infiltration of basophilic cells in inflamed tissue after injection of
      RANTES.
AB  - Regulated upon activation normal T expressed and secreted (RANTES) is a new
      inducible protein member of the human C-C branch of chemokines. RANTES is a
      potent monocyte and lymphocyte chemoattractant and is a mediator of inflammatory
      responses. In these studies we found that RANTES 10 ng/50 microl chemoattracts
      basophilic cells in a dose-dependent manner 4 h after an intradermal injection in
      rat skin sites, as revealed by optic microscopy. Moreover, in biopsy specimens
      from rat skin injection sites histamine release was significantly higher (P <
      0.05) than in controls (PBS 50 microl) after 4 h from RANTES treatment. The
      presence of basophilic cells in rat skin injection sites after RANTES-treatment
      was also confirmed by electron microscopy studies. In addition, histidine
      decarboxylase (HDC) mRNA was increased in rat skin sites injected with RANTES
      compared to sites injected with PBS (controls). Our report describes additional
      biological activities for RANTES, suggesting that this human chemoattractant
      protein may play a fundamental role in histamine and HDC generation, along with
      basophilic cell recruitment.

PMID- 9271321
TI  - Co-expression and secretion of C3, the third component of complement and a C3
      cleaving cysteine proteinase in a highly metastatic human melanoma cell line.
AB  - We recently demonstrated that DM-4, a human melanoma cell line highly metastatic
      in nude mice, expressed a p41 C3-cleaving proteinase. This p41 proteinase is a
      cysteine proteinase, associated to cell surface and involved in tumorigenicity
      and metastatic properties of these tumor cells. We demonstrate herein that DM-4
      cells also secrete the p41 proteinase. In addition, analysis of cellular
      components which reacted with the p41 proteinase led us to demonstrate that DM-4
      cells synthesized and secreted human C3. Secreted C3 is cleaved by the secreted
      p41 proteinase and a C3dg-like fragment is generated. This is the first
      demonstration that a human melanoma cell line co-expresses and co-secretes human
      C3 and a C3-cleaving cysteine proteinase, antigenically related to procathepsin
      L.

PMID- 9271322
TI  - Are free radicals responsible for endothelial cell killing of Staphylococcus
      aureus?
AB  - We have recently demonstrated that endothelial cells cultured on Gelfoam blocks,
      but not monolayer matrices can phagocytose and kill Staphylococcus aureus.
      Experiments determined that penicillin G, included in the endothelial cell growth
      medium, induces these cells to exhibit the observed bactericidal activity. In
      this communication, we report on studies aimed at elucidating the mechanism by
      which penicillin G-induced endothelial cells, cultured on Gelfoam blocks, kill S.
      aureus. Despite the fact that there is a substantial literature that demonstrates
      neutrophilic killing of bacteria can be mediated through free radical-dependent
      and free radical-independent mechanisms, considerably less is known about
      pathways by which endothelial cells can catalyze similar microbicidal activities.
      Studies described herein point to the fact that superoxide and products derived
      from this free radical were not responsible for endothelial killing of S. aureus.
      Likewise, a possible role for nitric oxide in bacterial killing was explored. As
      part of this inquiry, we stably transduced a NOS-2 encoding retrovirus into
      endothelial cells cultured on Gelfoam blocks in the absence of penicillin G. Even
      though these cells secreted nitric oxide at a rate of 0.5 microM/h per 1 x 10(6)
      cells, similar to what has been reported for murine macrophages induced with
      gamma-interferon, in our model, nitric oxide was not found to kill S. aureus.
      Data presented demonstrate that the microbicidal activity of endothelial cells is
      mediated through free radical-independent pathways.

PMID- 9271323
TI  - IL-6 is a survival prognostic factor in renal cell carcinoma.
AB  - It has been reported that a high plasmatic concentration of interleukin-6 (IL-6)
      is correlated to a lack of response to immunotherapy in several malignancies,
      suggesting that IL-6 was either a marker of tumour aggressiveness or had only a
      predictive value of response to immunotherapy. To discriminate between these two
      possibilities, a retrospective study was performed in a series of 19 patients
      with metastatic renal cell carcinoma who did not respond to IL-2/IFNalpha/5-FU
      treatment. Serum levels of IL-6, C-reactive Protein (CRP), soluble IL-2-receptor
      (sIL-2R), M-CSF and neopterin were assayed before treatment. IL-6 showed a
      significant correlation with patients median survival time (P < 0.016),
      suggesting that serum concentration of IL-6 before treatment is a marker of
      tumour aggressiveness rather than a predictive parameter for an immunological
      response.

PMID- 9271325
TI  - Intracellular diadenosine polyphosphates: a novel family of inhibitory ligands of
      the ATP-sensitive K+ channel.
AB  - Intracellular diadenosine polyphosphates (Ap(n)A) are signal molecules that alert
      the cell under stress conditions. Herein, we review evidence that has recently
      identified a novel target for Ap(n)A, namely the ATP-sensitive K+ (K(ATP))
      channel. These channels are abundant in pancreatic beta-cells and cardiac
      myocytes where they are essential in coupling the cellular metabolic state with
      membrane excitability. The potency and efficacy of Ap(n)A to inhibit K(ATP)
      channel activity were first described in cardiac K(ATP) channels, and appear
      similar to those of intracellular ATP, the primary ligand of K(ATP) channels.
      Also, the inhibitory ligand action of Ap(n)A is dependent upon the operative
      condition of K(ATP) channels and the presence of nucleotide diphosphates. In
      addition to a direct antagonism of channel opening, an indirect effect of Ap(n)A
      on K(ATP) channel activity has been associated with inhibition of adenylate
      kinase, a catalytic system believed essential for the regulation of channel
      opening. At present, the precise role for Ap(n)A-induced K(ATP) channel
      inhibition remains to be established. Yet, it is known that, under glucose
      challenge of pancreatic beta-cells, intracellular concentrations of Ap(n)A do
      increase to micromolar levels necessary to block K(ATP) channels, leading to
      insulin secretion. Thus, the Ap(n)A-mediated K(ATP) channel gating represents a
      previously unrecognized pathway of channel regulation.

PMID- 9271324
TI  - Erratum to "Relevance of the antibody response against human immunodeficiency
      virus type 1 envelope to vaccine design".
AB  - Understanding the antibody response in HIV-1 infection is important to vaccine
      design. We have studied the antibody response to HIV-1 envelope at the molecular
      level and determined the characteristics of neutralizing and non-neutralizing
      antibodies. These antibodies were isolated from phage display libraries prepared
      from long-term seropositive asymptomatic individuals. The HIV-1 envelope is
      presented to the immune system in several antigenically distinct configurations:
      unprocessed gp160, gp120 and gp41 subunits and native envelope, each of which may
      be important in eliciting an antibody response in HIV-1 infection. The antibodies
      tested characteristically had poor affinities for native envelope as expressed on
      the surface of virions or infected cells, but had high affinities against non
      native forms of HIV-1 envelope (viral debris). An exceptionally potent
      neutralizing antibody in contrast, bound native envelope with equivalent or
      somewhat higher affinity than this. This indicates that the antibody response in
      HIV-1 infection is principally elicited by viral debris rather than virions, and
      that these antibodies bind and neutralize viruses sub-optimally. Potential
      vaccines should be designed to elicit responses against native envelope.

PMID- 9271326
TI  - GTP regulation of (-)-stepholidine binding to R(H) of D1 dopamine receptors in
      calf striatum.
AB  - (-)-Stepholidine (SPD) exhibits antagonist effects on normosensitive dopamine
      (DA) receptors, but it has an agonist action on rotation in unilaterally 6
      hydroxydopamine (6-OHDA)-lesioned rats. The present work endeavors to further
      elucidate the mechanism of its agonist action on D1 receptors. [3H]R(+)-7-chloro
      8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-be nzazepine ([3H]SCH-23390)
      and [3H]spiperone were used, respectively, as radioligands in D1 and D2 DA
      receptor binding assays in calf striatal membranes. Experimental data were
      analyzed by a non-linear regression computer program, GraphPAD InPlot 3.15. The
      competition curves were fitted first by a single-site equation and then by a two
      site equation. The results showed that both apomorphine (APO) and SPD
      competitively inhibited [3H]SCH-23390 binding. Their competition curves fitted
      best to the two-site equation (P < 0.05) with a high-affinity site (R(H)) and a
      low-affinity site (R(L)) to DA receptors. The K(H) and K(L) values (nM) were 2.7
      +/- 0.45 and 378 +/- 62 for APO, and 3.9 +/- 2.2 and 126 +/- 25 for SPD,
      respectively. In contrast, the competition curve of SCH-23390, a selective D1 DA
      receptor antagonist, fitted best to a single-site model with a Ki value of 1.7 +/
      0.5 nM. The R(H) of APO or SPD could be decreased by the addition of 450 microM
      GTP. In the [3H]spiperone binding test, the APO curve was modeled best by the two
      site equation, while the SPD curve fitted best to a single-site model. In the
      rotational behavior test, APO induced 441 +/- 20 turns/30 min in the 6-OHDA
      lesioned rats, and SPD induced 310 +/- 42 turns/30 min, while SCH-23390
      antagonized the SPD-induced rotation but did not induce rotational behavior.
      These results suggest that SPD possesses agonist actions on D1 but antagonist
      effects on D2 DA receptors.

PMID- 9271327
TI  - Involvement of receptor reserve in D1 agonistic action of (-)-stepholidine in
      lesioned rats.
AB  - (-)-Stepholidine (SPD) is a natural product. Previous studies had demonstrated
      that SPD displayed D1 agonism in unilaterally 6-hydroxydopamine (6-OHDA)-lesioned
      rats and D1 antagonism in reserpinized rats and normal rats. The aim of the
      present study was to explain this peculiar pharmacological action based on
      behavioral and biochemical experiments. In the unilaterally 6-OHDA-lesioned rats,
      SPD (4 mg/kg, s.c.) induced contralateral rotation as did apomorphine (APO), but
      the rotation response to SPD was 60% lower than that to APO (0.5 mg/kg, i.p.).
      Coadministration with APO (0.5 mg/kg, i.p.) and SPD (0.5 to 10 mg/kg, s.c.)
      produced a biphasic action curve. At low doses (0.5 or 1 mg/kg), SPD potentiated
      APO action; at high doses (4 or 10 mg/kg), however, SPD suppressed APO. In
      striatal homogenate of the unilaterally lesioned rats, SPD stimulated cyclic AMP
      (cAMP) formation and produced a maximal response comparable to that of dopamine
      (DA) in the denervated striatum, but 70% lower than that of DA in the intact
      striatum. Coadministration of 10 microM DA with various concentrations of SPD
      yielded different results, with a biphasic response in the intact side and a
      synergistic effect in the denervated side. Furthermore, based on the
      determination of receptor-mediated cAMP formation, the D1 receptor reserve was
      analyzed in both denervated and intact striatum by using the DA receptor
      inactivator N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). The results
      showed that following EEDQ administration, the receptor density [revealed by
      [3H]R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-be
      nzazepine ([3H]SCH-23390) binding] and the agonist-stimulated adenylate cyclase
      (AC) activity (revealed by cAMP formation) were reduced concurrently. In the
      intact striatum, the reduction in SPD-stimulated AC activity paralleled the
      receptor loss, indicating the absence of receptor reserve, while in the
      denervated striatum the reduction in AC activity was less than the receptor loss,
      indicating a significant level of receptor reserve (estimated 16.4%). By
      comparison, receptor reserve for DA was 45.7 and 25.3% in the denervated and
      intact striatum, respectively, representing an 80% increase of receptor reserve.
      In conclusion, SPD is a D1 partial agonist, and receptor reserve permits SPD to
      display its D1 agonistic action in the unilaterally 6-OHDA-lesioned rats.

PMID- 9271328
TI  - Activation of parietal cell by mercaptomethylimidazole: a novel inducer of
      gastric acid secretion.
AB  - Mercaptomethylimidazole (2-Mercapto-1-methylimidazole, MMI), an antithyroid drug
      of thionamide group, significantly activated the parietal cell for acid
      secretion, as evidenced by increased O2 consumption by more than 2.5-fold over
      the basal level. When compared, MMI-induced activation was similar to that of
      histamine but significantly higher than that of isobutylmethylxanthine or
      carbachol. Activation by MMI was not prevented by receptor blockers of the
      parietal cell, indicating that its effect was not mediated through the cell
      surface histamine-H2 receptor or the muscarinic receptor. However, the activation
      was almost completely blocked only by omeprazole, an established inhibitor of the
      terminal proton-pumping H+-K+-ATPase of the parietal cell. That MMI-induced
      activation was coupled with the H+ transport was further confirmed by significant
      increase in [14C]-aminopyrine uptake by MMI in rabbit gastric gland preparation.
      MMI-dependent activation of the parietal cell correlated well with the inhibition
      of the endogenous peroxidase activity. In vitro studies indicated that MMI
      irreversibly inactivated both peroxidase and catalase activity of the parietal
      cell in presence of H2O2. As inactivation of these H2O2-scavenging enzymes should
      increase accumulation of intracellular H2O2, the effect of latter was studied on
      acid secretion. H2O2 at a low concentration, stimulated acid secretion by
      sevenfold in isolated gastric mucosa, which was sensitive to omeprazole. It also
      significantly stimulated [14C]-aminopyrine uptake in gastric gland preparation.
      We suggest that MMI activated parietal cells to stimulate acid secretion by
      endogenous accumulation of H2O2 through inactivation of the peroxidase-catalase
      system.

PMID- 9271329
TI  - Adaptation of human tumor cells to tirapazamine under aerobic conditions:
      implications of increased antioxidant enzyme activity to mechanism of aerobic
      cytotoxicity.
AB  - Tirapazamine (TPZ, 3-amino-1,2,4-benzotriazine 1,4-di-N-oxide, SR 4233, WIN
      59075) is a bioreductive antitumor agent with a high selective toxicity for
      hypoxic cells. The selective hypoxic toxicity of TPZ results from the rapid
      reoxidation of the one-electron reduction product, the TPZ radical, in the
      presence of molecular oxygen with the concomitant production of superoxide
      radical. Under hypoxia the TPZ radical kills cells by causing DNA double-strand
      breaks and chromosome aberrations. However, the mechanism of aerobic cytotoxicity
      is still a matter of debate. In this study, we investigated the mechanism of
      aerobic cytotoxicity by adapting human lung adenocarcinoma A549 cells to aerobic
      TPZ exposure and characterizing the changes associated with drug resistance. The
      adapted cells were resistant to aerobic TPZ exposures (with dose-modifying
      factors of up to 9.2), although hypoxic sensitivity was largely unchanged.
      Relative to the parental A549 cell line, adaptation to continuous aerobic TPZ
      exposure resulted in increased levels of manganese superoxide dismutase (up to
      9.4-fold), moderate increases in glutathione reductase (up to 2.1-fold), and loss
      of both quinone oxidoreductase (DT-diaphorase) activity and NADPH cytochrome P450
      reductase activity. There was essentially no change in the activity of the
      cytoplasmic form of superoxide dismutase (CuZnSOD), catalase, or glutathione
      peroxidase. The increased activity of antioxidant enzymes in the resistant cell
      lines (in particular MnSOD) strongly suggests that reactive oxygen species are,
      in large part, responsible for the toxicity of TPZ under aerobic conditions, and
      is consistent with aerobic and hypoxic drug cytotoxicity resulting from different
      mechanisms.

PMID- 9271331
TI  - Mutant acetylcholinesterases as potential detoxification agents for
      organophosphate poisoning.
AB  - It has been demonstrated that cholinesterases (ChEs) are an effective mode of
      pretreatment to prevent organophosphate (OP) toxicity in mice and rhesus monkeys.
      The efficacy of ChE as a bioscavenger of OP can be enhanced by combining enzyme
      pretreatment with oxime reactivation, since the scavenging capacity extends
      beyond a stoichiometric ratio of ChE to OP. Aging has proven to be a major
      barrier to achieving oxime reactivation of acetylcholinesterase (AChE) inhibited
      by the more potent OPs. To further increase the stoichiometry of OP to ChE
      required, we have sought AChE mutants that are more easily reactivated than wild
      type enzyme. Substitution of glutamine for glutamate (E199) located at the amino
      terminal to the active-site serine (S200) in Torpedo AChE generated an enzyme
      largely resistant to aging. Here we report the effect of the corresponding
      mutation on the rate of inhibition, reactivation by 1-(2-hydroxyiminomethyl-1
      pyridinium)-1(4-carboxyaminopyridinium)- dimethyl ether hydrochloride (HI-6), and
      aging of mouse AChE inhibited by C(+)P(-)- and C(-)P(-)-epimers of soman. The
      E202 to Q mutation decreased the affinity of soman for AChE, slowed the
      reactivation of soman-inhibited AChE by HI-6, and decreased the aging of mutant
      AChE. These effects were more pronounced with C(-)P(-)-soman than with C(+)P(-)
      soman. In vitro detoxification of soman and sarin by wild-type and E202Q AChE in
      the presence of 2 mM HI-6 showed that, E202Q AChE was 2-3 times more effective in
      detoxifying soman and sarin than wild-type AChE. These studies show that these
      recombinant DNA-derived AChEs are a great improvement over wild-type AChE as
      bioscavengers. They can be used to develop effective methods for the safe
      disposal of stored OP nerve agents and potential candidates for pre- or post
      exposure treatment for OP toxicity.

PMID- 9271330
TI  - Thromboxane A2 synthase inhibition and thromboxane A2 receptor blockade by 2-[(4
      cyanophenyl)amino]-3-chloro-1,4-naphthalenedione (NQ-Y15) in rat platelets.
AB  - The effects of 2-[(4-acetylphenyl)amino]-3-chloro-1,4-naphthalenedione (NQ-Y15),
      a synthetic 1,4-naphthoquinone derivative, on platelet activity and its mechanism
      of action were investigated. NQ-Y15 caused a concentration-dependent inhibition
      of the aggregation induced by thrombin, collagen, arachidonic acid (AA), and
      A23187. The IC50 values of NQ-Y15 on thrombin (0.1 U/mL)-, collagen (10
      microg/mL)-, AA (50 microM)-, and A23187 (2 microM)-induced aggregation were 36.2
      +/- 1.5, 6.7 +/- 0.7, 35.4 +/- 1.7, and 93.1 +/- 1.4 microM, respectively. NQ-Y15
      also inhibited thrombin-, collagen-, AA-, and A23187-stimulated serotonin
      secretion in a concentration-dependent manner. However, a high concentration (100
      microM) of NQ-Y15 showed no significant inhibitory effect on ADP-induced primary
      aggregation, which is independent of thromboxane A2 (TXA2) production in rat
      platelets. In fura-2-loaded platelets, the elevation of intracellular free
      calcium concentration stimulated by AA, thrombin, and 4-bromo-A23187 was
      inhibited by NQ-Y15 in a concentration-dependent manner. The formation of TXA2
      caused by AA, thrombin, and collagen was inhibited significantly by NQ-Y15. NQ
      Y15 inhibited TXA2 synthase in intact rat platelets, since this agent reduced the
      conversion of prostaglandin (PG) H2 to TXA2. Similarly, NQ-Y15 selectively
      inhibited the TXA2 synthase activity in human platelet microsomes, whereas it had
      no effect on activity of phospholipase A2, cyclooxygenase, and PGI2 synthase in
      vitro. NQ-Y15 inhibited platelet aggregation induced by the endoperoxide analogue
      U46619 in human platelets, indicating TXA2 receptor antagonism, possibly of a
      competitive nature. These results suggest that the antiplatelet effect of NQ-Y15
      is due to a combination of TXA2 synthase inhibition with TXA2 receptor blockade,
      and that it may be useful as an antithrombotic agent.

PMID- 9271332
TI  - Activation of sodium transport and intracellular sodium lowering by the
      neuroleptic drug chlorpromazine.
AB  - Chlorpromazine (CPZ), a commonly used antipsychotic drug, at high concentration
      was found to reduce significantly the sodium content of both rat (Rattus
      norvegicus) and toad (Bufo marinus) liver cells. This reduction in intracellular
      sodium was demonstrated using 22Na+ flux and measurement of cell sodium content.
      The results suggest that the sodium-lowering effect of CPZ stemmed from a
      stimulation of sodium transport rather than from an inhibition of sodium influx
      (i.e., sodium channels), cell damage, or Na+:Na+ exchange. CPZ was found to
      interfere with the binding of ouabain to the sodium pump, although a simple
      reduction in sodium pump inhibition did not account for the sodium-lowering
      effect. CPZ was able to negate the effects of monensin, a sodium ionophore,
      suggesting a substantial capacity to activate sodium transport. The intracellular
      sodium-lowering action of CPZ through the activation of sodium transport
      represents a new property previously undescribed for this drug.

PMID- 9271333
TI  - Bradykinin antagonists in human systems: correlation between receptor binding,
      calcium signalling in isolated cells, and functional activity in isolated ileum.
AB  - The determination of the relationship between ligand affinity and bioactivity is
      important for the understanding of receptor function in biological systems and
      for drug development. Several physiological and pathophysiological functions of
      bradykinin (BK) are mediated via the B2 receptor. In this study, we have examined
      the relationship between B2 receptor (soluble and membrane-bound) binding of BK
      peptidic antagonists, inhibition of calcium signalling at a cellular level, and
      in vitro inhibition of ileum contraction. Only human systems were employed in the
      experiments. Good correlations between the studied activities of BK antagonists
      were observed for a variety of different peptidic structures. The correlation
      coefficients (r) were in the range of 0.905 to 0.955. In addition, we analyzed
      the effect of the C-terminal Arg9 removal from BK and its analogs on B2 receptor
      binding. The ratios of binding constants (Ki(+Arg)/Ki(-Arg)) for the Arg9
      containing compounds and the corresponding des-Arg9 analogs varied from about 10
      to 250,000. These ratios strongly depend on the chemical structures of the
      compounds. The highest ratios were observed for two natural agonist pairs, BK/des
      Arg9-BK and Lys0-BK/des-Arg9-Lys0-BK.

PMID- 9271334
TI  - Fenspiride and membrane transduction signals in rat alveolar macrophages.
AB  - Fenspiride inhibits the calcium signal evoked by the inflammatory peptide formyl
      Met-Leu-Phe (fMLP) in peritoneal macrophages, but at concentrations
      (approximately 1 mM) far above the therapeutic range (approximately 1 microM).
      Here, in rat alveolar macrophages, high fenspiride concentrations (1 mM) were
      required to inhibit the calcium signals evoked by the calcium agonist Bay K8644
      or by ionomycin. Moreover, fenspiride (1 mM) was a poor inhibitor of the cell
      membrane depolarization induced by gramicidine D. By contrast, fenspiride blocked
      Na+-H+ antiport activation by (i) fMLP with an IC50 = 3.1 +/- 1.9 nM and (ii) PMA
      (phorbol 12-myristate 13-acetate) with an IC50 = 9.2 +/- 3.1 nM. Finally, protein
      kinase C (PKC) activity of macrophage homogenate was not significantly modified
      by 10 or 100 microM fenspiride (at 100 microM: 2.57 +/- 1.60 vs. 2.80 +/- 1.71
      pmol/10(6) cells/min). In conclusion, fenspiride inhibits fMLP- and PMA-induced
      pH signals in rat alveolar macrophages, probably by acting distally on the PKC
      transduction signal. This pH antagonistic action may be relevant for the
      antiinflammatory mechanism of fenspiride and requires further investigation.

PMID- 9271335
TI  - Calcyclin gene expression modulation by medroxyprogesterone acetate.
AB  - Calcyclin is a cell-cycle-related gene corresponding to a calcium-binding protein
      whose expression is mainly controlled by platelet-derived growth factor. This
      paper illustrates medroxyprogesterone acetate (MPA) inhibition of endogenous
      calcyclin RNA expression of both estrogen-dependent human mammary carcinoma cells
      and estrogen-independent hamster fibroblasts. Transfection of fragments of the
      calcyclin promoter driving the chloramphenicol-acetyl-transferase (CAT) gene into
      hamster fibroblasts was used to evaluate the hormone sensitivity of different
      promoter regions by considering calcyclin expression at both the RNA and protein
      level, as evaluated by the CAT assay. A 164 bp promoter fragment showed a good
      activity that was inhibited by MPA, thereby confirming the results of the
      observation of endogenous calcyclin gene: smaller fragments, however, required
      cotransfection of progestin receptor to show full activity, with MPA displaying a
      stimulatory effect. These findings show that progestin modulation of calcyclin
      gene expression may be independent of progestin receptors, and that MPA has
      opposite effects on different promoter regions.

PMID- 9271336
TI  - Ah receptor-dependent CYP1A induction by two carotenoids, canthaxanthin and beta
      apo-8'-carotenal, with no affinity for the TCDD binding site.
AB  - The assays of several phase I and phase II xenobiotic-metabolizing enzyme
      activities, as well as CYP1A immunoblot analysis, were performed in liver
      microsomes and cytosol of male C57BL/6 mice (Ah receptor-responsive), of male
      DBA/2 mice (Ah receptor-low responsive) and of female Ah receptor gene knockout
      mice that were fed diets containing 300 mg/kg of a nonprovitamin A carotenoid,
      canthaxanthin, or a provitamin A carotenoid, beta-apo-8'-carotenal for 14 days,
      or which were injected i.p. with 3-methylcholanthrene. Previous studies have
      shown that some carotenoids, such as canthaxanthin and beta-apo-8'-carotenal, are
      strong inducers of liver CYP1A1 and 1A2 when given to rats. In this work, only
      canthaxanthin induced both CYP1A1 and 1A2 in C57BL/6 mice, whereas beta-apo-8'
      carotenal induced only CYP1A2 in this strain. Neither of the two carotenoids
      modified CYP1A1/2 protein contents or enzyme activities in Ah receptor-low
      responsive DBA/2 or in Ah receptor gene knockout mice. Cytosol prepared from
      C57BL/6 mice liver tissue was incubated with [3H] 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) in the presence of canthaxanthin or beta-apo-8'-carotenal and
      analyzed by sucrose density gradient sedimentation: neither of the carotenoids,
      even when present in large excess, competed with TCDD for the TCDD binding site
      of the cytosolic Ah receptor of C57BL/6 mice. In brief, the carotenoids
      canthaxanthin or beta-apo-8'-carotenal induced Cyp1a genes in mice through an Ah
      receptor-dependent pathway, but did not bind to the Ah receptor.

PMID- 9271337
TI  - Methylenedioxy group as determinant of schisandrin in enhancing hepatic
      mitochondrial glutathione in carbon tetrachloride-intoxicated mice.
AB  - As a preliminary approach to exploring whether the methylenedioxy group of the
      dibenzocyclooctadiene skeleton of schisandrins plays an important role in hepatic
      mitochondrial-reduced glutathione (GSH) stimulatory activity, we examined the
      effects of three schisandrins, namely schisandrin A (Sch A), schisandrin B (Sch
      B), and schisandrin C (Sch C), on carbon tetrachloride (CCl4) hepatotoxicity and
      hepatic mitochondrial GSH status in mice. Pretreating mice with Sch A at a daily
      oral dose of 1 mmol/kg for 3 days did not protect against CCl4 hepatotoxicity,
      whereas pretreatment with Sch B or Sch C at the same dosage regimen produced
      almost complete protection. The hepatoprotection afforded by Sch B or Sch C
      pretreatment was associated with significant increases in the hepatic
      mitochondrial GSH level and glutathione reductase (EC 1.6.4.2) activity. Our
      results indicate that the methylenedioxy group of the dibenzocyclooctadiene
      skeleton of schisandrin is an important structural determinant in the stimulation
      of hepatic mitochondrial GSH, particularly under conditions of CCl4 intoxication.

PMID- 9271338
TI  - Class II pyrethroids: noninhibitors calcineurin.
AB  - Type II pyrethroid insecticides have been reported to be potent inhibitors of
      bovine brain calcineurin (EC 3.1.3.16, Enan E and Matsumara F, Biochem Pharmacol
      43: 1777-1784, 1992). In concentrations up to 10(-5) M, none of the pyrethroid
      insecticides used in this study caused inhibition of the calcineurin-dependent
      dephosphorylation of the 19-amino acid phosphopeptide derived from the regulatory
      subunit R-II of the cyclic adenosine 3',5'-monophosphate (cAMP)-dependent protein
      kinase, which has been established as a good substrate for this enzyme. Neither
      did any of the compounds tested cause a shift in the inhibitory activity of
      okadaic acid (apparent Ki of 5 microM). The assumption that calcineurin is
      generally inhibited by pyrethroid insecticides is incorrect, and the
      interpretation of cellular experiments in which this assumption has been made
      must be revised.

PMID- 9271340
TI  - An efficacy-dependent effect of cardiac overexpression of beta2-adrenoceptor on
      ligand affinity in transgenic mice.
AB  - In previous studies, it was shown that the overexpression of beta2-adrenoceptor
      (beta2AR) in the hearts of transgenic mice (Tg) leads to agonist-independent
      activation of adenylate cyclase and enhanced myocardial function. Here, we
      measured the physical coupling of beta2AR and Gs by evaluating the
      coimmunoprecipitation of beta2AR and Gs and the ligand binding properties of
      beta2AR in the hearts of Tg mice to investigate the details of the interaction
      among ligand, receptor, and G protein. The following results were obtained: (i)
      coimmunoprecipitation of beta2AR and Gs was increased in the absence of agonist
      in Tg mice compared with the control animals. This demonstrates directly the
      increased interaction between unliganded beta2AR and Gs, which is consistent with
      increased background cAMP production and cardiac function in the hearts of Tg
      mice. (ii) Guanosine-5'-(beta,gamma-imido)triphosphate abolished the association
      of beta2AR/Gs in the immunoprecipitate. (iii) The affinities for ligands that
      show agonist (isoproterenol, clenbuterol, and dobutamine), neutral antagonist
      (alprenolol and timolol), and negative antagonist (propranolol and ICI 118551)
      activities in this experimental system were increased, not changed and decreased,
      respectively, in Tg mice compared with the controls. (iv) This efficacy-dependent
      alteration in ligand affinities was still observed in the presence of a guanosine
      5'-(beta,gamma-imido)triphosphate concentration that abolishes beta2AR/Gs
      coupling. This suggests that the altered beta2AR binding affinities in Tg mice
      are not due to the increased interaction between beta2AR and Gs. These data
      cannot be explained by using ternary, quinternary, two-state extended ternary, or
      cubic ternary complex models. We therefore discuss the results using a "two-state
      polymerization model" that includes an isomerization step for the conversion of
      receptor between an inactive and an active form (denoted as R and R*,
      respectively) and a polymerization of the active state (R*n). The simplest form
      of this model (i.e., noncooperative dimerization of the receptor) is found to be
      consistent with the experimental data.

PMID- 9271339
TI  - Activation of type II adenylate cyclase by D2 and D4 but not D3 dopamine
      receptors.
AB  - The D2-like dopamine receptors couple to a variety of signal transduction
      pathways, including inhibition of adenylate cyclase, mitogenesis, and activation
      of potassium channels. Although these effects are mediated via pertussis toxin
      sensitive G proteins, G(i/o), it is likely that some of these effects are
      influenced by the release of G protein betagamma subunits. Type II adenylate
      cyclase (ACII) is highly regulated by multiple biochemical stimuli, including
      protein kinase C, forskolin, G protein alpha subunits, and G protein betagamma
      subunits. The ability of betagamma subunits to activate this enzyme in the
      presence of activated alpha(s) has been particularly well characterized. Although
      stimulation by betagamma subunits has been described as conditional on the
      presence of activated alpha(s), betagamma subunits also potentiate ACII activity
      after activation of protein kinase C. We created stable cell lines expressing
      ACII and the D2L receptor, the D3 receptor, or the D4.4 receptor. Activation of
      D2L or D4.4 receptors, but not D3 receptors, potentiated beta-adrenergic
      receptor/Gs-stimulated activity of ACII, as measured by the intracellular
      accumulation of cAMP. Similarly, stimulation of D2L or D4.4 receptors potentiated
      phorbol ester-stimulated ACII activity in the absence of activated alpha(s),
      whereas stimulation of D3 receptors did not. The effect of D2-like receptor
      stimulation was blocked by pretreatment with pertussis toxin and by inhibition of
      protein kinase C. We propose that activation of both D2L and D4.4 dopamine
      receptors potentiated phorbol-12-myristate-13-acetate-stimulated ACII activity
      through the release of betagamma subunits from pertussis toxin-sensitive G
      proteins. In contrast, the lack of D3 receptor-mediated effects suggests that
      stimulation of D3 receptors does not result in an appreciable release of
      betagamma subunits.

PMID- 9271341
TI  - Enhanced apoptosis in metallothionein null cells.
AB  - Metallothioneins (MTs) are major intracellular, zinc-binding proteins with
      antioxidant properties. Mouse embryonic cells null for MT due to loss of
      functional MT I and II genes (MT-/-) were more susceptible to apoptotic death
      after exposure to tert-butyl hydroperoxide or the anti-cancer agents cytosine
      arabinoside, bleomycin, melphalan, and cis-dichlorodiammineplatinum(II) compared
      with wild-type mouse embryonic cells (MT+/+). We measured basal levels of the
      tumor suppressor protein p53 and the death effector protein Bax and found the
      basal levels of both proteins were higher in MT null cells compared with MT+/+
      cells. After treatment with the DNA-damaging agent cis
      dichlorodiammineplatinum(II), p53 protein levels were induced in both MT+/+ and
      MT-/- cells with MT null cells always maintaining the highest p53 levels. The
      elevated sensitivity to apoptosis was not restricted to embryonic cells. Primary
      pulmonary fibroblasts were isolated from distinct litters of MT null,
      heterozygous, and wild-type mice, and all had undetectable basal MT levels. Zinc
      exposure increased MT levels in the wild-type and heterozygous fibroblasts but
      not in the MT null fibroblasts. Consistent with the induced MT levels, we found
      MT+/+ and MT+/- embryonic cells were less sensitive to cis
      dichlorodiammineplatinum(II)-induced apoptosis compared with MT-/- cells. Our
      results implicate MT as a stress-responsive factor that can regulate apoptotic
      engagement.

PMID- 9271342
TI  - Determination of aryl hydrocarbon receptor nuclear translocator protein
      concentration and subcellular localization in hepatic and nonhepatic cell culture
      lines: development of quantitative Western blotting protocols for calculation of
      aryl hydrocarbon receptor and aryl hydrocarbon receptor nuclear translocator
      protein in total cell lysates.
AB  - Western blot analysis was used to determine the concentration of the aryl
      hydrocarbon receptor nuclear translocator (ARNT) protein and aryl hydrocarbon
      receptor (AHR) in 11 mammalian cell culture lines derived from hepatic and
      nonhepatic tissues. The strategy was to first use Western blot analysis to
      determine the expression of ARNT or AHR in each cell line relative to its
      concentration in murine wild-type Hepa-1c1c7 (Hepa-1) cells. Actual ARNT and AHR
      concentrations in known amounts of total cell lysates were then determined by
      generating a standard curve with defined amounts of a highly purified ARNT or AHR
      protein and performing regression analysis. The results show that the level of
      ARNT expression in each of the cell lines is similar and represents approximately
      0.001-0.002% of total cellular protein. The range of expression was only
      approximately 3-fold with wild-type Hepa-1 cells expressing the highest level of
      ARNT (33,000/cell) and canine kidney cells (MDCK line) expressing 14,000 ARNT
      molecules/cell. In contrast, the concentration of AHR varied by 65-fold over the
      different cell lines with the wild-type Hepa-1 expressing 323,000 AHR/cell and
      rat hepatoma cells (H4IIE) expressing 4700. The ratio of AHR to ARNT ranged from
      0.3 in H4IIE cells to 10 in the Hepa-1 line with the majority of cells expressing
      1-5 times more AHR than ARNT protein. Immunocytochemical staining of each cell
      line showed that ARNT was exclusively localized to the nuclear compartment and
      that a conserved nuclear localization signal mapped to the NH-terminal portion of
      the protein.

PMID- 9271343
TI  - Differential expression of the UGT1A locus in human liver, biliary, and gastric
      tissue: identification of UGT1A7 and UGT1A10 transcripts in extrahepatic tissue.
AB  - Family 1 UDP-glucuronosyltransferases (UGTs) (UGT1A) are encoded by a locus that
      predicts the existence of at least nine individual proteins. The different
      proteins are generated by exon-sharing, which results in the production of a
      family of proteins that contain identical, 245-amino acid, carboxyl-terminal
      domains and an amino-terminal region of approximately 280 amino acids. The
      diversity of the UGT1A locus suggests the existence of complex regulation, most
      likely designed to account for the variable and specific glucuronidation
      requirements. However, the tissue-specific and extrahepatic regulation of the
      complete UGT1A locus has not been defined to date. In this study, quantitative
      duplex reverse transcription-polymerase chain reaction was used to analyze UGT1A
      RNA expression in 16 hepatic, four biliary, and two gastric human tissue
      specimens. UGT1A3 and UGT1A6 were found to be expressed in the three tissues,
      whereas UGT1A5 and UGT1A8 were not expressed. Hepatocellular and biliary tissue
      expressed UGT1A1 and UGT1A4 but hepatocellular tissue uniquely expressed UGT1A9,
      whereas biliary tissue expressed UGT1A10. In contrast to hepatocellular tissue,
      gastric tissue expressed UGT1A7 in addition to UGT1A10. The expression of UGT1A9
      in hepatic tissue, UGT1A7 in gastric tissue, and UGT1A10 in biliary and gastric
      tissue provides evidence for the selective regulation of the UGT1A locus in
      hepatic and extrahepatic tissues. The newly identified UGT1A7 and UGT1A10
      transcripts were cloned and found to be 95.86% identical. Sequence analysis
      confirmed two proteins with divergent amino termini of 285 residues and identical
      carboxyl termini of 245 residues. This study provides evidence for hepatic and
      extrahepatic regulation of the human UGT1A locus and identifies two novel
      extrahepatic transcripts of the UGT1A family.

PMID- 9271344
TI  - 5-hydroxytryptamine1A receptor-mediated increases in receptor expression and
      activation of nuclear factor-kappaB in transfected Chinese hamster ovary cells.
AB  - The regulation in expression of human 5-hydroxytryptamine1A (5-HT1A) receptors by
      agonists and antagonists was studied in a stable transfected Chinese hamster
      ovary cell line expressing the human 5-HT1A receptor. Receptor density and
      affinity were measured with [125I]4-(2'-methoxyphenyl)-1-[2'-[N-(2'-pyridinyl)-p
      iodobenzamido ]ethyl]piperazine ([125I]p-MPPI), a selective antagonist of 5-HT1A
      receptors. Treatment of Chinese hamster ovary cells with serotonin or the
      selective agonist (+/-)-8-hydroxy-N,N-dipropyl-2-aminotetralin stimulated a 2.5
      fold increase in receptor density. The antagonists 4-(2'-methoxyphenyl)-1-[2'-[N
      (2'-pyridinyl)-p-iodobenzamidoethyl] piperazine, (-)-(S)-pindolol, and spiperone
      also stimulated up-regulation of receptor expression. Agonist- and antagonist
      stimulated up-regulations of receptor expression were mechanistically different.
      The effect of agonists was inhibited by pertussis toxin, actinomycin D, and
      cycloheximide. Antagonist-stimulated up-regulation was inhibited by
      cycloheximide, only partially inhibited by actinomycin D, and not inhibited by
      pertussis toxin. In the course of identifying potential pathways for coupling of
      the receptor to activation of transcription, we demonstrated that agonists
      activate the transcription regulatory factor nuclear factor-kappaB (NF-kappaB).
      Agonists were found to stimulate degradation of the inhibitory subunit, IkappaB
      alpha, and to increase the activity of a NF-kappaB-dependent CAT reporter gene.
      In contrast, the antagonist 4-(2'-methoxyphenyl)-1-[2'-[N-(2'-pyridinyl)-p
      iodobenzamidoethyl] piperazine neither elicited degradation of Ikappa-B alpha nor
      increased reporter activity. Our data suggest that expression of 5-HT1A receptors
      can be regulated by both agonists and antagonists and that the agonist but not
      antagonist stimulation occurs concomitantly with activation of NF-kappaB.

PMID- 9271345
TI  - Arginine-glycine-aspartic acid mimics can identify a transitional activation
      state of recombinant alphaIIb beta3 in human embryonic kidney 293 cells.
AB  - The platelet-specific integrin alphaIIb beta3 achieves a high affinity binding
      state in response to extracellular agonists such as thrombin, ADP, or collagen.
      During this activation, the receptor undergoes a number of conformational
      changes. To characterize the different conformations of alphaIIb beta3, we
      expressed recombinant alphaIIb beta3 in human embryonic kidney (HEK) 293 cells.
      Antigenic and peptide recognition specificities of the full-length recombinant
      receptor resembled those of the native receptor in platelets. We used an array of
      peptidic and nonpeptidic arginine-glycine-aspartic acid (RGD) mimics that
      specifically bind to human platelet alphaIIb beta3 to determine the affinity
      state of the receptor. Some of these RGD mimics were previously shown to clearly
      discriminate between resting and activated alphaIIb beta3. Solution-phase binding
      of these RGD mimics to the recombinant cells suggested that in HEK 293 cells the
      full-length alphaIIb beta3 is expressed in a "transitional" activation state.
      This observation was confirmed by the binding of the activation-specific,
      monoclonal anti-alphaIIb beta3 antibody PAC1 to cells expressing the full-length
      recombinant alphaIIb beta3. Deletion of the entire cytoplasmic domain of the beta
      subunit was sufficient to convert the receptor in HEK 293 cells to a fully active
      form, as found in activated platelets. In addition, the full-length receptor was
      capable of mediating agonist-independent aggregation of cells in the presence of
      fibrinogen. Thus, by using RGD mimics, we have identified a functional
      transitional activation state of alphaIIb beta3 that is capable of mediating
      fibrinogen-dependent cell aggregation.

PMID- 9271346
TI  - Localization and functional expression of splice variants of the P2X2 receptor.
AB  - cDNAs encoding three splice variants of the P2X2 receptor were isolated from rat
      cerebellum. The first variant has a serine/proline-rich segment deleted from the
      intracellularly located carboxyl-terminal domain of the P2X2 subunit. The second
      and third variants have the splice site in the second half of the predicted first
      transmembrane domain. Either a 12-amino acid insertion or a six-amino acid
      deletion occurs at this position. cRNAs for these isoforms of the P2X2 subunit
      were injected into Xenopus laevis oocytes and tested for function. ATP evoked
      inward currents only with the splice variant [designated P2X2(b)] having the 69
      amino acid deletion. The potencies of various agonists at the homomeric P2X2(b)
      receptor were not significantly different from those at the P2X2(a) homomeric
      channel. However, the P2X2(b) receptor showed significantly lower antagonist
      sensitivity. In contrast to the nondesensitizing P2X2(a) receptor, prolonged
      application of ATP produced a more rapid desensitization of the P2X2(b) receptor.
      When the P2X2(a) and P2X2(b) receptor responses were recorded in transfected
      mammalian cells, this difference was again found. The change in desensitization
      may be determined by proline/serine-rich segments and/or phosphorylation motifs
      that are removed from the tail region in formation of the P2X2(b) subunit. In
      situ hybridization of the three newly isolated isoforms of the P2X2 subunit was
      performed at the macroscopic and cellular levels; transcripts for two of them
      [P2X2(b) and p2x2(c)] but not the third [p2x2(d)], which carries the 12-amino
      acid addition, were present in many structures in the neonatal rat brain and on
      sensory and sympathetic ganglia. mRNA for the p2x2(d) splice variant was present
      only in the nodose ganglion, at a low level.

PMID- 9271347
TI  - Inhibition of O6-alkylguanine DNA-alkyltransferase or poly(ADP-ribose) polymerase
      increases susceptibility of leukemic cells to apoptosis induced by temozolomide.
AB  - High levels of expression of the DNA repair enzyme O6-alkylguanine DNA
      alkyltransferase (OGAT) (EC 2.1.1.63) account for tumor cell resistance to
      methylating agents. Previous studies suggested that methylating triazenes might
      have a potential role for the treatment of acute leukemias with low levels of
      OGAT. In the current study, we transduced the human OGAT cDNA in OGAT-deficient
      leukemia cell clones. OGAT-transduced cells were more resistant than their OGAT
      deficient counterparts to apoptosis triggered by the methylating triazene
      temozolomide (TZM), as indicated by the results of flow cytometry, terminal
      deoxynucleotidyl transferase assay, and analysis of DNA fragmentation. Depletion
      of OGAT activity by O6-benzylguanine increased leukemia cell sensitivity to TZM
      mediated apoptosis. Moreover, combined treatment of cells with TZM and benzamide,
      an inhibitor of the poly(ADP-ribose) polymerase (EC 2.4.2.30), increased the
      apoptosis induced by the methylating agent. These results demonstrate for the
      first time that methyl adducts at the O6 position of guanine, which are
      specifically removed by OGAT, are the principal DNA lesions responsible for the
      induction of apoptosis on treatment of leukemic cells with the methylating
      triazene TZM. This study also supports the possible use of TZM for the treatment
      of acute leukemias and suggests new strategies to increase the susceptibility of
      tumor cells to methylating triazenes in the clinic.

PMID- 9271349
TI  - Cimetidine and other H2-receptor antagonists as inhibitors of human E3 aldehyde
      dehydrogenase.
AB  - The histamine H2-receptor antagonists have been identified as inhibitors of human
      liver aldehyde dehydrogenase (EC 1.2.1.3) isozymes, E1, E2, and E3. Inhibition
      was strongest with the E3 isozyme, whose substrates include gamma
      aminobutyraldehyde, the aldehyde metabolites of polyamines, and betaine aldehyde.
      Burimamide, metiamide, cimetidine guanidine, cimetidine, and tiotidine were
      competitive with aldehyde substrates and noncompetitive with the coenzyme,
      binding to both the free E3 isozyme and the enzyme-coenzyme binary complex.
      Cimetidine and tiotidine were the best inhibitors, with Ki values of 1.1 +/- 0.2
      microM and 1.0 +/- 0.0 microM, respectively; both are the first ever described
      potent and selective inhibitors of the E3 isozyme. Examination of the H2-receptor
      antagonist structures for insight into the moieties accounting for E3 isozyme
      inhibition pointed to the side-chain polar groups as strongly influencing
      inhibition, with the cyanoguanidine side chain of cimetidine and tiotidine having
      the strongest influence. The Ki value of the E3 isozyme for cimetidine was the
      same as the in vitro dissociation constant for the H2-receptor.

PMID- 9271348
TI  - Identification of conserved aromatic residues essential for agonist binding and
      second messenger production at 5-hydroxytryptamine2A receptors.
AB  - Several models of agonist binding to G protein-coupled 5-hydroxytryptamine [5-HT]
      (serotonin) receptors have highlighted the potential importance of highly
      conserved aromatic residues for ligand binding and agonist efficacy. In this
      study, we tested these models by constructing and characterizing a number of
      point mutations of conserved and nonconserved aromatic residues using the 5-HT2A
      receptor as a model system. Mutations of three highly conserved tryptophans
      (W200A, W336A, and W367A) proposed to reside near the binding pocket markedly
      reduced agonist affinity and efficacy at 5-HT2A receptors. Mutations of two other
      highly conserved aromatic residues postulated to be near the agonist binding site
      (F340L and Y370A) also had dramatic effects on agonist binding and efficacy.
      Point mutations of neighboring conserved phenylalanines (F339L and F365L) had
      minimal effects on agonist binding, although the F365L mutation diminished
      agonist efficacy. Finally, mutations of two nonconserved aromatic residues (F125L
      and F383A) not predicted to be near the binding pocket had no effects on agonist
      binding, potency, or efficacy. Our results are best explained by models that
      suggest that helices III, V, VI, and VII can form a unit of interacting helices
      in which highly conserved aromatic residues are oriented toward the center of the
      helical aggregate to form an aromatic pocket. In addition, our novel results
      identify a series of aromatic residues essential for agonist-induced second
      messenger production. These results demonstrate that highly conserved aromatic
      residues residing in neighboring helices provide the optimum environment for both
      agonist binding and activation of 5-HT2A receptors.

PMID- 9271350
TI  - Opioid regulation of the mouse delta-opioid receptor expressed in human embryonic
      kidney 293 cells.
AB  - Opioid analgesics are used extensively in the management of pain. Although the
      clinically effective opioids bind with high affinity to the mu-opioid receptor,
      studies have suggested that the delta-opioid agonists might represent more ideal
      analgesic agents, with fewer side effects. A limitation to opiate effectiveness
      is the development of tolerance, an event that has been linked to opioid receptor
      desensitization. To gain a better understanding of delta-receptor agonist
      regulation, the cloned mouse delta receptor was stably expressed in human
      embryonic kidney 293 cells, and the functional effects of agonist pretreatment
      were examined. With a 3-hr pretreatment protocol, the delta-selective agonists [D
      Pen2,D-Pen5]enkephalin, [D-Ala2,D-Leu5]enkephalin, and [D-Ser2,Leu5]enkephalin
      Thr and the nonselective opioids levorphanol, etorphine, and ethylketocyclazocine
      were found to desensitize delta receptors. [D-Pen2,D-Pen5]enkephalin, [D
      Ser2,Leu5]enkephalin-Thr, [D-Ala2,D-Leu5]enkephalin, and etorphine treatments
      also caused a pronounced internalization of the epitope-tagged delta receptor,
      suggesting that the desensitization and internalization may be related. In
      contrast, levorphanol pretreatment did not internalize the receptor but still
      resulted in a 400-fold reduction in potency, suggesting that prolonged treatment
      with levorphanol only uncoupled the delta receptor from adenylyl cyclase. In
      contrast to the desensitization induced by peptide-selective delta agonists,
      pretreatment with the delta-selective nonpeptide agonist 7
      spiroindanyloxymorphone and morphine sensitized the opioid inhibition of
      forskolin-stimulated cAMP accumulation. This differential regulation of the delta
      receptor may be due to variations in the ability of agonists to bind to the
      receptor. This hypothesis was supported by the finding that a point mutation that
      converted Asp128 to Asn128 (D128N) diminished the ability of delta-selective
      agonists to inhibit cAMP accumulation while increasing the potency of morphine to
      reduce cAMP accumulation. In particular, a lack of desensitization of the delta
      receptor by morphine may contribute to our understanding of the molecular basis
      of development of morphine-induced tolerance and dependence.

PMID- 9271351
TI  - Regulation of human neuronal calcium channels by G protein betagamma subunits
      expressed in human embryonic kidney 293 cells.
AB  - We examined the ability of different G protein subunits to inhibit the activity
      of human alpha1B and alpha1E Ca2+ channels stably expressed in human embryonic
      kidney (HEK) 293 cells together with beta1B and alpha2Bdelta Ca2+ channel
      subunits. Under normal conditions, Ca2+ currents in alpha1B-expressing cells
      showed little facilitation after a depolarizing prepulse. However, when we
      overexpressed the beta2gamma2 subunits of heterotrimeric G proteins, the time
      course of activation of the Ca2+ currents was considerably slowed and a
      depolarizing prepulse produced a large facilitation of the current as well as an
      acceleration in its time course of activation. Similar effects were not observed
      when cells were transfected with constitutively active mutants of the G protein
      alpha subunits alpha s, alpha i1, and alpha o or with the G protein beta2 and
      gamma2 subunits alone. Studies carried out in cells expressing alpha1E currents
      showed that overexpression of beta2gamma2 subunits produced pre-pulse
      facilitation, although this was of lesser magnitude than that observed with Ca2+
      currents in alpha1B-expressing cells. The subunits beta2 and gamma2 alone
      produced no effects, nor did constitutively active alpha s, alpha i1, and alpha o
      subunits. Phorbol esters enhanced alpha1E Ca2+ currents but had no effect on
      alpha1B currents, suggesting that protein kinase C activation was not responsible
      for the observed effects. When alpha1E Ca2+ currents were expressed without their
      beta subunits, they exhibited prepulse facilitation. These results demonstrate
      that alpha1E Ca2+ currents are less susceptible to direct modulation by G
      proteins than alpha1B currents and illustrate the antagonistic interactions
      between Ca2+ channel beta subunits and G proteins.

PMID- 9271352
TI  - CholecystokininB receptor from human Jurkat lymphoblastic T cells is involved in
      activator protein-1-responsive gene activation.
AB  - The aim of this study was to analyze the role of cholecystokinin (CCK(B))
      receptor in human lymphoblastic Jurkat T cells. We investigated the trophic
      effect resulting from activation of such a receptor by using the reporter gene
      strategy. For this purpose, we transiently transfected Jurkat T cells with the
      reporter plasmid p[(TRE)3-tk-Luc] and found that CCK-8 was able to dose
      dependently induce luciferase expression related to activator protein-1 (AP-1)
      activation with a maximal response identical to that obtained with compounds
      known to activate AP-1 complex (quantitatively, the same level of induction was
      obtained with 1 nM 12-O-tetradecanoylphorbol-13-acetate, 100 microM
      diacylglycerol, or 4 nM epidermal growth factor). The involvement of the CCK(B)
      receptor in such a stimulation was demonstrated by the inhibiting effect of the
      selective CCK(B) receptor antagonist PD-135,158. This effect was confirmed in COS
      7 cells transfected with the cDNA of CCK(B) receptor cloned from Jurkat T cells.
      To better understand the AP-1-dependent luciferase expression in Jurkat T cells,
      we tested two specific inhibitors of serine/threonine phosphatases-1 and -2A:
      okadaic acid and calyculin A. These compounds strongly increased the phorbol-12
      myristate-13-acetate response, whereas we have not observed a contribution of
      phosphatase inhibitors on a CCK-8-induced luciferase activity. To confirm that
      CCK(B) receptors are involved in AP-1 response, we investigated the CCK-8 effect
      on interleukin-2 expression, a natural endogenous gene regulated by several
      factors, including AP-1. In Jurkat T cells activated by phorbol-12-myristate-13
      acetate and phytohemagglutinin, CCK-8 induced IL-2 expression. This induction was
      abolished by PD-135,158. Our results indicate that CCK-8 exerts a trophic effect
      in Jurkat T cells through stimulation of CCK(B) receptors by modulation of
      expression of AP-1-regulated genes.

PMID- 9271353
TI  - The reduction of alpha-tocopherolquinone by human NAD(P)H: quinone
      oxidoreductase: the role of alpha-tocopherolhydroquinone as a cellular
      antioxidant.
AB  - alpha-Tocopherolquinone (TQ), a product of alpha-tocopherol oxidation, can
      function as an antioxidant after reduction to alpha-tocopherolhydroquinone
      (TQH2). We examined the ability of human NAD(P)H:quinone oxidoreductase (NQO1) to
      catalyze the reduction of TQ to TQH2 in cell-free and cellular systems. In
      reactions with purified human NQO1, TQ was reduced to TQH2. Kinetic parameters
      for the reduction of TQ by NQO1 (Km = 370 microM; k(cat) = 5.6 x 10(3) min(-1);
      k(cat)/Km = 15 min(-1) x microM(-1)) indicate that NQO1 can efficiently reduce TQ
      to TQH2. A comparison of the rate of reduction of TQ and coenzyme Q10 by NQO1
      showed that TQ is reduced more efficiently than coenzyme Q10. Experiments with
      either Chinese hamster ovary (CHO) cells stably transfected with human NQO1 or
      CHO cell sonicates demonstrated a correlation between NQO1 activity and TQ
      reduction to TQH2. CHO cells with elevated NQO1 generated and maintained higher
      levels of TQH2 after treatment with TQ relative to NQO1-deficient CHO cells. TQH2
      generated from NQO1-mediated reduction of TQ prevented cumene hydroperoxide
      induced lipid peroxidation in rat liver microsomes. In addition, cumene
      hydroperoxide-induced lipid peroxidation was inhibited more efficiently by TQ in
      CHO cell lines with elevated NQO1 activity. These data demonstrate that NQO1 can
      reduce TQ to TQH2 and that TQH2 can function as an efficient antioxidant. This
      work suggests that one of the physiological functions of NQO1 may be to
      regenerate antioxidant forms of alpha-tocopherol.

PMID- 9271354
TI  - A mutation in the hamster alpha1B-adrenergic receptor that differentiates two
      steps in the pathway of receptor internalization.
AB  - An NP(X)nY motif is highly conserved among G protein-coupled receptors and is
      similar to an NPXY motif involved in receptor-mediated endocytosis for several
      non-G protein-coupled receptors. We investigated the role of this motif in
      alpha1B-adrenergic receptor function and regulation. Y348A alpha1B-adrenergic
      receptors in which this sequence was mutated from NPIIY to NPIIA were prepared by
      site-directed mutagenesis and transfected into Chinese hamster ovary cells.
      Binding of the antagonist prazosin to Y348A receptors was similar to that of wild
      type receptors, but affinity of the Y348A receptors for the agonist epinephrine
      was increased by approximately 10-fold. Despite this increase in agonist binding
      affinity, the Y348A mutation completely uncoupled the receptors from stimulation
      of phosphoinositide hydrolysis and mobilization of intracellular Ca2+. Exposure
      of cells expressing Y348A receptors to the agonist epinephrine resulted in
      receptor "sequestration," defined as a loss of cell surface receptors accessible
      to radioligand in binding assays with intact cells on ice, similar to that for
      the wild-type receptor. In contrast, Y348A receptors did not undergo
      "endocytosis" into the light vesicle fraction in sucrose density gradient
      centrifugation assays, as did the wild-type receptor. These results (i) indicate
      an important role for Tyr348 in coupling the alpha1B-adrenergic receptor to G
      protein and subsequent effector activation, (ii) provide further evidence that
      alpha1B-adrenergic receptor internalization can be separated into a sequestration
      step and an endocytosis step, (iii) indicate that effector activation and second
      messenger formation are not required for the sequestration of these receptors but
      may be involved in endocytosis, and (iv) provide a useful new tool for further
      investigation of the nature of the subcellular compartments and the molecular
      modifications involved in the multiple steps involved in internalization of G
      protein-coupled receptors.

PMID- 9271355
TI  - Interactions of the nonsedating antihistamine loratadine with a Kv1.5-type
      potassium channel cloned from human heart.
AB  - The use of nonsedating antihistamines may, on rare occasions, be associated with
      cardiac arrhythmias. This could be due to blockade of voltage-dependent K+
      channels in the heart, leading to a prolongation in repolarization in the human
      myocardium. For this reason, we examined the effects of the nonsedating
      antihistamine loratadine on a rapidly activating delayed-rectifier K+ channel
      (Kv1.5) cloned from human heart and stably expressed in HEK 293 cells or mouse
      Ltk- cells. Using patch-clamp electrophysiology, we found that loratadine blocked
      Kv1.5 current measured from inside-out membrane patches at concentrations of > or
      = 100 nM, resulting in an IC50 value of 808 nM at +50 mV. The drug enhanced the
      rate of Kv1.5 current decay, and block was enhanced at membrane potentials near
      threshold relative to higher potentials. Loratadine did not alter the kinetics of
      Kv1.5 current activation or deactivation. Unitary Kv1.5 currents were recorded in
      cell-attached patches. At the single-channel level, the main effect of loratadine
      was to reduce the mean probability of opening of Kv1.5. This effect of loratadine
      was achieved by a reduced number of openings in bursts and burst duration.
      Finally, loratadine (10 microM) failed to inhibit HERG K+ channel currents
      expressed in Xenopus laevis oocytes. It is concluded that loratadine is an
      effective blocker of Kv1.5 that interacts with an activated state or states of
      the channel. This interaction suggests a potential for loratadine to alter
      cardiac excitability in vivo.

PMID- 9271356
TI  - Quantitative structure-activity relationship of multidrug resistance reversal
      agents.
AB  - Multidrug resistance (MDR) is one of the major obstacles to long term successful
      cancer chemotherapy. The use of MDR reversal (MDRR) agents is a promising
      approach to overcome the undesired MDR phenotype. To design more effective MDRR
      agents that are urgently needed for clinical use, a data set of 609 diverse
      compounds tested for MDRR activity against P388/ADR-resistant cell lines was
      submitted to the MULTICASE computer program for structure-activity analysis. Some
      substructural features related to MDRR activity were identified. For example, the
      CH2-CH2-N-CH2-CH2 group was found in most of the active compounds, and the
      activity was further enhanced by the presence of (di)methoxylphenyl groups,
      whereas the presence of a stable quaternary ammonium salt, a carboxylic, a
      phenol, or an aniline group was found to be detrimental to activity. Possible
      explanations for these observations are proposed. Some physicochemical
      properties, e.g., the partition coefficient (log P) and the graph index (which in
      some sense measures the "complexity" of a molecule) were also found to be
      relevant to activity. Their role in MDRR was also rationalized. Based on our
      quantitative structure-activity relationship study of MDRR agents, some compounds
      with desired substructural features and activity were identified from the MACCS
      II and National Cancer Institute DIS databases and tested experimentally. Our
      study may also help the rational design of anti-cancer drugs. Based on this study
      and on observations by other researchers, we postulate that P-glycoprotein
      mediated resistance to paclitaxel could probably be eliminated by proper
      substitution of its benzamido and phenyl groups. Several novel compounds with the
      paclitaxel skeleton are proposed, which may lead to a new generation of
      paclitaxel anti-cancer drugs with less MDR potential.

PMID- 9271357
TI  - Hard days on the endless frontier.

PMID- 9271358
TI  - The making and breaking of symmetry in virus capsid assembly: glimpses of capsid
      biology from cryoelectron microscopy.
AB  - Virus capsids constitute a diverse and versatile family of protein-bound
      containers and compartments ranging in diameter from approximately 200 A (mass
      approximately 1 MDa) to >1500 A (mass>250 MDa). Cryoelectron microscopy of
      capsids, now attaining resolutions down to 10 A, is disclosing novel structural
      motifs, assembly mechanisms, and the precise locations of major epitopes. Capsids
      are essentially symmetric structures, and icosahedral surface lattices have
      proved to be widespread. However, many capsid proteins exhibit a remarkable
      propensity for symmetry breaking, whereby chemically identical subunits in
      distinct lattice sites have markedly different structures and packing
      relationships. Temporal differences in the conformation of a given subunit are
      also manifested in the large-scale conformational changes that accompany capsid
      maturation. Larger and more complex capsids, such as DNA bacteriophages and
      herpes simplex virus, are formed not by simple self-assembly, but under the
      control of tightly regulated programs that may include the involvement of viral
      scaffolding proteins and cellular chaperonins, maturational proteolysis, and
      conformational changes on an epic scale. In addition to its significance for
      virology, capsid-related research has implications for biology in general,
      relating to the still largely obscure assembly processes of macromolecular
      complexes that perform many important cellular functions.

PMID- 9271359
TI  - Journey from cachexia to obesity by TNF.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a cytokine involved in the
      physiological and metabolic abnormalities found in cachectic states. Until very
      recently, it was inconceivable to think of TNF-alpha in obesity. However, recent
      studies have shown that TNF-alpha can also play a key role in obesity, the
      cytokine being overexpressed in adipose tissue of obese rodents and humans. The
      aim of this review is to reconcile the role of TNF-alpha in these two opposite
      metabolic situations: obesity and cachexia. It is suggested that TNF-alpha may
      have a key role in the control of body mass in normal weight-controlled
      situations and that abnormalities in either its production (during cachexia) or
      action (during obesity) are responsible for the lack of control of body weight.

PMID- 9271360
TI  - Genetic immunization: a new era in vaccines and immune therapeutics.
AB  - DNA inoculation represents a novel approach to vaccine and immune therapeutic
      development. The direct injection of gene expression cassettes into a living host
      transforms a number of cells into factories for production of the introduced gene
      products. Expression of these delivered genes has important immunological
      consequences and may result in the specific immune activation of the host against
      the novel expressed antigens. The recent demonstration by laboratories that these
      immune responses are protective in some infectious disease experimental models as
      well as cancers is viewed with cautious optimism. Further, the relatively short
      development times, ease of large-scale production, low development,
      manufacturing, and distribution costs all combine with immunological
      effectiveness to suggest that this technology will dramatically influence the
      production of a new generation of experimental vaccines and immune therapies. It
      is hoped that DNA inoculation will ultimately lead to new vaccines that are
      immunologically effective and economically accessible to all nations.

PMID- 9271361
TI  - Interferon-inducible protein-10 and lymphotactin induce the chemotaxis and
      mobilization of intracellular calcium in natural killer cells through pertussis
      toxin-sensitive and -insensitive heterotrimeric G-proteins.
AB  - We show here that interferon-inducible protein-10 (IP-10), an ELR lacking CXC
      chemokine, and the C chemokine lymphotactin (Ltn) induce the chemotaxis and
      calcium mobilization in IL2-activated NK (IANK) and CC chemokine-activated NK
      (CHAK) cells. Cross-desensitization experiments show that IP-10 or Ltn use
      receptors not shared by other C, CC, or CXC chemokines. The chemotaxis induced by
      either IP-10 or Ltn for both cell types is inhibited upon pretreatment of these
      cells with pertussis toxin (PT). Also, Ltn-induced [Ca2+]i in IANK but not in
      CHAK cells is inhibited upon pretreatment with PT, whereas IP-10-induced [Ca2+]i
      in IANK and CHAK cells is inhibited upon pretreatment with this toxin. These
      results suggest important roles for PT-sensitive and -insensitive G-proteins in
      IP-10-induced and Ltn-induced chemotaxis and calcium fluxes in activated NK
      cells. This was further implicated after streptolysin O permeabilization of CHAK
      and IANK cells and after introduction of inhibitory antibodies to the PT
      sensitive Gi and Go or the PT-insensitive Gq. Our results suggest that IP-10 and
      Ltn receptors are coupled to Gi, Go, and Gq in IANK cells and to Gi and Gq in
      CHAK cells, with a possible low coupling of IP-10, but not of Ltn, receptors to
      Go in these cells. Together, these results show that IP-10 and Ltn-dependent
      chemotaxis and calcium mobilization may differentiate at the level of receptor
      coupling to the heterotrimeric G-proteins.

PMID- 9271362
TI  - CD4 memory T cell levels predict life span in genetically heterogeneous mice.
AB  - Aging leads to changes in the relative proportions of several functionally
      distinct T cell subsets, including increases in the proportions of memory cells
      in the CD4 and CD8 subsets and in the proportion of T cells expressing the
      multiple-drug resistance pump P-glycoprotein. To see whether individual
      differences in T cell subset levels predict life span, we measured the levels of
      five age-sensitive T cell subsets, at 8 and again at 18 months of age, in the
      peripheral blood of genetically heterogeneous mice bred as the progeny of CB6F1
      females and C3D2F1 males. The strongest immunological predictor of life span in
      univariate regression analyses was the proportion of CD4 memory cells measured at
      18 months of age (P=0.003). CD4 memory cell levels remained strongly correlated
      with life span (P<0.0003) in a multiple regression analysis after adjustment for
      sex. The proportion of CD4 cells expressing P-glycoprotein was also correlated
      with life span (P<0.01), but only in male mice. Weaker relationships were
      observed between life span and 8-month tests of CD8 memory and CD8 P-glycoprotein
      levels, for CD4 naive cells at 18 months, and for the change in CD4 naive cells
      between 8 and 18 months of age; these were, however, near the margin of
      statistical significance and could reflect chance relationships. The relationship
      between CD4 memory cell levels and life span was similarly strong regardless of
      the cause of death in mice whose death was attributable to lymphoma,
      fibrosarcoma, mammary carcinoma, and other forms of terminal pathology.
      Additional work is needed to discriminate between two hypotheses: 1) that high
      levels of CD4 memory cell themselves predispose to disease and early death,
      particularly from neoplasia; or 2) that accumulation of CD4 memory cells is a
      biomarker of some underlying process-perhaps accelerated aging-that itself leads
      to early mortality.

PMID- 9271363
TI  - Release of the aspartyl protease cathepsin D is associated with and facilitates
      human breast cancer cell invasion.
AB  - Data concerning the hormone sensitivity of the release and role of the aspartyl
      protease cathepsin D in tumor proliferative and invasive processes have been
      contradictory. To clarify the mechanisms of its release and role we first studied
      the contribution of estradiol and stripped serum to the time course and kinetics
      of cathepsin D release, proliferation, and invasion in parallel in the MCF-7 in
      vitro breast cancer cell culture model. Both estradiol and stripped serum
      independently stimulated both proliferation and cathepsin D release. However, the
      dose-response of estradiol and stripped serum-dependent stimulated release were
      similar to those for invasion and differed from those for proliferation:
      cathepsin D release and invasion were first stimulated at a stripped serum
      concentration more than 10-fold lower than that which initiated proliferation and
      had half stimulation constants almost 10-fold lower than those for proliferation.
      These results demonstrate that cathepsin D release is not related in any direct
      way to proliferation. The effect of the reduction of cathepsin D activity or
      release on in vitro invasion was also measured: both the inhibition of secreted
      cathepsin D activity by a specific inhibitor, diazoacetyl-DL-Nle-OMe, and the
      reduction of cathepsin D release by antisense oligonucleotides against its
      translation start site reduced cellular in vitro invasion without affecting
      proliferation. Cathepsin D release and activity are concluded to be directly
      involved in the process of invasion.

PMID- 9271364
TI  - Roles of NO and Ca2+-activated K+ channels in coronary vasodilation induced by
      17beta-estradiol in ischemic heart failure.
AB  - Estrogen induces the generation of nitric oxide (NO) and produces coronary
      vasodilation by opening the Ca2+-activated K+ (K[Ca]) channels. The hypothesis
      that 17beta-estradiol produces NO and activates K(Ca) channels during coronary
      hypoperfusion was investigated. In open-chest dogs, the left anterior descending
      coronary artery was perfused through an extracorporeal bypass tube from the left
      carotid artery. 17beta-Estradiol was infused into the bypass tube for 20 min
      after coronary blood flow was reduced by partial occlusion of the bypass tube.
      17beta-Estradiol increased the difference in NO concentrations between the
      coronary venous and arterial blood as well as coronary blood flow. The lactate
      extraction ratio and pH of coronary venous blood were both also increased by
      17beta-estradiol, indicating a reduction in myocardial anaerobic metabolism.
      Whereas the increase in the coronary arteriovenous difference in NO concentration
      was completely attenuated by N(G)-nitro-L-arginine methyl ester (L-NAME, an
      inhibitor of NO synthase), the increase in coronary blood flow induced by 17beta
      estradiol was only partially attenuated by L-NAME. The combination of L-NAME and
      iberiotoxin (a blocker of high-conductance K(Ca) channels) completely abolished
      the coronary vasodilatory effect of 17beta-estradiol. The data indicate that
      during coronary hypoperfusion in canine hearts, 17beta-estradiol increases
      coronary blood flow and improves metabolic dysfunction by increasing NO release
      and opening K(Ca) channels.

PMID- 9271365
TI  - Apoptosis in Xenopus tadpole tail muscles involves Bax-dependent pathways.
AB  - Apoptosis is a fundamental mechanism implicated in normal development. One of the
      most spectacular developmental events involving apoptosis is tail regression
      during amphibian metamorphosis. We analyzed how thyroid hormone (3, 5, 3'
      triiodothyronine, T3), the orchestrator of metamorphosis, affects expression and
      function of the proapoptotic gene Bax in the tail muscle of free-living Xenopus
      tadpoles. During natural metamorphosis Bax mRNA was expressed in tail muscles and
      was spatially correlated with apoptosis. Precocious treatment of tadpoles with T3
      induced Bax expression and apoptosis. To verify that Bax expression was causally
      related to apoptosis we used a naked DNA gene transfer method to express Bax in
      the dorsal tail muscle. This induced apoptosis, and the process was exacerbated
      by T3 treatment. To determine whether T3 effects on Bax expression involved
      transcriptional regulation, we injected a Bax promoter sequence into dorsal and
      caudal tail muscles. In the dorsal muscle, T3 treatment did not affect
      transcription from the Bax promoter. However, in the caudal muscle, T3 treatment
      significantly increased Bax transcription. We conclude that T3-induced apoptosis
      in Xenopus tadpole tail muscles involves Bax-activating and Bax-synergis tic
      mechanisms. These programs are induced in spatially and temporally distinct
      manners.

PMID- 9271366
TI  - A role for uncoupling protein-2 as a regulator of mitochondrial hydrogen peroxide
      generation.
AB  - According to the state of mitochondrial respiration, the respiratory chain
      generates superoxide anions converted into hydrogen peroxide. Two uncoupling
      proteins (UCP) able to modulate the coupling between the respiratory chain and
      ATP synthesis are now identified and could be involved in mitochondrial H2O2
      generation. UCP1 is specific to brown adipose tissue (BAT) whereas UCP2 is
      expressed in numerous tissues, particularly in monocytes/macrophages.
      Preincubation of BAT mitochondrial fractions with GDP, an inhibitor of UCP1,
      induced a rise in mitochondrial membrane potential (assessed by rhodamine 123
      uptake) and H2O2 production. An uncoupling agent reversed this effect. Liver
      mitochondria exhibited a similar phenotype. GDP was also able to raise membrane
      potential and H2O2 production of the mitochondria from nonparenchymal cells
      expressing UCP2, but was completely ineffective on mitochondria from hepatocytes
      deprived of UCP2. The GDP effect was also observed with mitochondrial fractions
      of the spleen or thymus, which highly expressed UCP2. Altogether, these results
      strongly suggest that UCP2 is sensitive to GDP and that the UCPs, particularly
      UCP2, are able to modulate H2O2 mitochondrial generation. This supports a role
      for UCP2 in cellular (patho-) physiological processes involving free radicals
      generated by mitochondria, such as oxidative damage, inflammation, or apoptosis.

PMID- 9271367
TI  - Simultaneous assessment of conformation and aggregation of beta-amyloid peptide
      using electrospray ionization mass spectrometry.
AB  - Electrospray ionization mass spectrometry was used to study conformation and
      aggregation of the synthetic beta-amyloid peptide, residues 1-40 (betaA4), as a
      function of concentration and sample aging. All mass spectra showed a major
      envelope of peaks corresponding to charge states of 7-3 of the monomeric form of
      betaA4. In addition, weaker envelopes of peaks corresponding to charge states of
      dimeric, trimeric, and tetrameric betaA4 species were seen under gentle
      ionization conditions. The average charge state of the envelope associated with
      the monomeric form decreased by ca. 0.5 z as samples were aged, indicating that
      the relatively open form (likely random coil) of the peptide was modified into
      the more compact form (likely beta-sheet) as a function of sample aging. The
      aggregate forms became weaker and ultimately were absent both in the more dilute
      solutions and in aged aliquots of the concentrated sample. These aggregates were
      interpreted as assemblies of the random coil form. We interpret our inability to
      see an ion envelope that can be associated with aggregates of the beta-sheet form
      to be a consequence of the presumed very compact nature of this form. A model for
      the formation of betaA4 fibrils is proposed and discussed.

PMID- 9271369
TI  - Disruption of a gene encoding a novel mitochondrial DEAD-box protein in
      Trypanosoma brucei affects edited mRNAs.
AB  - The majority of mitochondrial pre-mRNAs in kinetoplastid protozoa such as
      Trypanosoma, Leishmania, and Crithidia are substrates of a posttranscriptional
      processing reaction referred to as RNA editing. The process results in the
      insertion and, to a lesser extent, deletion of uridylates, thereby completing the
      informational content of the mRNAs. The specificity of the RNA editing reaction
      is provided by guide RNAs (gRNAs), which serve as templates for the editing
      apparatus. In addition, the process relies on mitochondrial proteins, presumably
      acting within a high-molecular-mass ribonucleoprotein complex. Although several
      enzymatic activities have been implicated in the editing process, no protein has
      been identified to date. Here we report the identification of a novel
      mitochondrial DEAD-box protein, which we termed mHel61p. Disruption of the mHEL61
      alleles in insect-stage Trypanosoma brucei cells resulted in a reduced growth
      rate phenotype. On a molecular level, the null mutant showed significantly
      reduced amounts of edited mRNAs, whereas never-edited and nuclear mRNAs were
      unaffected. Reexpression of mHel61p in the knockout cell line restored the
      ability to efficiently synthesize edited mRNAs. The results suggest an
      involvement of mHel61p in the control of the abundance of edited mRNAs and thus
      reveal a novel function for DEAD-box proteins.

PMID- 9271368
TI  - Methylation of an ETS site in the intron enhancer of the keratin 18 gene
      participates in tissue-specific repression.
AB  - The activities of ETS transcription factors are modulated by posttranscriptional
      modifications and cooperation with other proteins. Another factor which could
      alter the regulation of genes by ETS transcription factors is DNA methylation of
      their cognate binding sites. The optimal activity of the keratin 18 (K18) gene is
      dependent upon an ETS binding site within an enhancer region located in the first
      intron. The methylation of the ETS binding site was correlated with the
      repression of the K18 gene in normal human tissues and in K18 transgenic mouse
      tissues. Neither recombinant ETS2 nor endogenous spleen ETS binding activities
      bound the methylated site effectively. Increased expression of the K18 gene in
      spleens of transgenic mice by use of an alternative, cryptic promoter 700 bp
      upstream of the enhancer resulted in modestly decreased methylation of the K18
      ETS site and increased RNA expression. Expression in transgenic mice of a mutant
      K18 gene, which was still capable of activation by ETS factors but was no longer
      a substrate for DNA methylation of the ETS site, was fivefold higher in spleen
      and heart. However, expression in other organs such as liver and intestine was
      similar to that of the wild-type gene. This result suggests that DNA methylation
      of the K18 ETS site may be functionally important in the tissue-specific
      repression of the K18 gene. Epigenetic modification of the binding sites for some
      ETS transcription factors may result in a refractory transcriptional response
      even in the presence of necessary trans-acting activities.

PMID- 9271370
TI  - Ribosome stalling is responsible for arginine-specific translational attenuation
      in Neurospora crassa.
AB  - The Neurospora crassa arg-2 upstream open reading frame (uORF) plays a role in
      negative arginine-specific translational regulation. Primer extension inhibition
      analyses of arg-2 uORF-containing RNA translated in a cell-free system in which
      arginine-specific regulation was retained revealed "toeprints" corresponding to
      ribosomes positioned at the uORF initiation and termination codons and at the
      downstream initiation codon. At high arginine concentrations, the toeprint signal
      corresponding to ribosomes at the uORF termination codon rapidly increased; a
      new, broad toeprint that represents additional ribosomes stalled on the uORF
      appeared 21 to 30 nucleotides upstream of this site; and the toeprint signal
      corresponding to ribosomes at the downstream initiation codon decreased. These
      data suggest that arginine increases ribosomal stalling and thereby decreases
      translation from the downstream initiation codon.

PMID- 9271371
TI  - Functional domains of the human orphan receptor ARP-1/COUP-TFII involved in
      active repression and transrepression.
AB  - The orphan receptor ARP-1/COUP-TFII, a member of the chicken ovalbumin upstream
      promoter transcription factor (COUP-TF) subfamily of nuclear receptors, strongly
      represses transcriptional activity of numerous genes, including several
      apolipoprotein-encoding genes. Recently it has been demonstrated that the
      mechanism by which COUP-TFs reduce transcriptional activity involves active
      repression and transrepression. To map the domains of ARP-1/COUP-TFII required
      for repressor activity, a detailed deletion analysis of the protein was
      performed. Chimeric proteins in which various segments of the ARP-1/COUP-TFII
      carboxy terminus were fused to the GAL4 DNA binding domain were used to
      characterize its active repression domain. The smallest segment confering active
      repressor activity to a heterologous DNA binding domain was found to comprise
      residues 210 to 414. This domain encompasses the region of ARP-1/COUP-TFII
      corresponding to helices 3 to 12 in the recently published crystal structure of
      other members of the nuclear receptor superfamily. It includes the AF-2 AD core
      domain formed by helix 12 but not the hinge region, which is essential for
      interaction with a corepressor in the case of the thyroid hormone and retinoic
      acid receptor. Attachment of the nuclear localization signal from the simian
      virus 40 large T antigen (Flu tag) to the amino terminus of ARP-1/COUP-TFII
      abolished its ability to bind to DNA without affecting its repressor activity. By
      using a series of Flu-tagged mutants, the domains required for transrepressor
      activity of the protein were mapped. They include the DNA binding domain and the
      segment spanning residues 193 to 399. Transcriptional activity induced by liver
      enriched transactivators such as hepatocyte nuclear factor 3 (HNF-3), C/EBP, or
      HNF-4 was repressed by ARP-1/COUP-TFII independent of the presence of its cognate
      binding site, while basal transcription or transcriptional activity induced by
      ATF or Sp1 was not perturbed by the protein. In conclusion, our results
      demonstrate that the domains of ARP-1/COUP-TFII required for active repression
      and transrepression do not coincide. Moreover, they strongly suggest that
      transrepression is the predominant mechanism underlying repressor activity of ARP
      1/COUP-TFII. This mechanism most likely involves interaction of the protein with
      one or several transcriptional coactivator proteins which are employed by various
      liver-enriched transactivators but not by ubiquitous factors such as Sp1 or ATF.

PMID- 9271372
TI  - The murine Sim-2 gene product inhibits transcription by active repression and
      functional interference.
AB  - The Drosophila single-minded (Dsim) gene encodes a master regulatory protein
      involved in cell fate determination during midline development. This protein is a
      member of a rapidly expanding family of gene products possessing basic helix-loop
      helix (bHLH) and hydrophobic PAS (designated a conserved region among PER, ARNT
      [aryl hydrocarbon receptor nuclear translocator] and SIM) protein association
      domains. Members of this family function as central transcriptional regulators in
      cellular differentiation and in the response to environmental stimuli such as
      xenobiotics and hypoxia. We have previously identified a murine member of this
      family, called mSim-2, showing sequence homology to the bHLH and PAS domains of
      Dsim. Immunoprecipitation experiments with recombinant proteins indicate that
      mSIM-2 associates with the arnt gene product. In the present work, by using fine
      structure mapping we found that the HLH and PAS motifs of both proteins are
      required for optimal association. Forced expression of GAL4/mSIM-2 fusion
      constructs in mammalian cells demonstrated the presence of two separable
      repression domains within the carboxy terminus of mSIM-2. We found that mSIM-2 is
      capable of repressing ARNT-mediated transcriptional activation in a mammalian two
      hybrid system. This effect (i) is dependent on the ability of mSIM-2 and ARNT to
      heterodimerize, (ii) is dependent on the presence of the mSIM-2 carboxy-terminal
      repression domain, and (iii) is not specific to the ARNT activation domain. These
      results suggest that mSIM-2 repression activity can dominantly override the
      activation potential of adjacent transcription factors. We also demonstrated that
      mSIM-2 can functionally interfere with hypoxia-inducible factor 1alpha (HIF
      1alpha)/ARNT transcription complexes, providing a second mechanism by which mSIM
      2 may inhibit transcription.

PMID- 9271373
TI  - Hepatocyte nuclear factor 1alpha gene inactivation impairs chromatin remodeling
      and demethylation of the phenylalanine hydroxylase gene.
AB  - Hepatocyte nuclear factor 1 alpha (HNF1alpha) is a homeoprotein that is expressed
      in the liver, kidney, pancreas, and digestive tract. Its inactivation in mouse
      resulted in decreased transcription of known target genes such as albumin and
      alpha1-antitrypsin. In contrast, the phenylalanine hydroxylase (PAH) gene was
      totally silent and unresponsive to normal inducers like glucocorticoids and
      cyclic AMP in the liver. DNase I and micrococcal nuclease digestion of liver
      nuclei showed that HNF1alpha inactivation had drastic effects on the chromatin
      structure of the PAH regulatory regions. Three DNase I-hypersensitive sites
      (HSSI, HSSII, and HSSIII), typical of the actively transcribed PAH gene, were
      undetectable in liver from HNF1alpha-deficient animals. Both HSSII and HSSIII
      elements harbor HNF1 sites, but only the latter has detectable enhancer activity
      in transient-transfection assays. In addition, the PAH promoter in livers of
      HNF1alpha-deficient animals was methylated. These results suggest that HNF1alpha
      could activate transcription through two mechanisms. One implies participation in
      the recruitment of the general transcription machinery to the promoter, and the
      second involves the remodeling of chromatin structure and demethylation that
      would allow transcription factors to interact with their cognate cis-acting
      elements.

PMID- 9271374
TI  - Interaction of ATF6 and serum response factor.
AB  - Serum response factor (SRF) is a transcription factor which binds to the serum
      response element (SRE) in the c-fos promoter. It is required for regulated
      expression of the c-fos gene as well as other immediate-early genes and some
      tissue-specific genes. To better understand the regulation of SRF, we used a
      yeast interaction assay to screen a human HeLa cell cDNA library for SRF
      interacting proteins. ATF6, a basic-leucine zipper protein, was isolated by
      binding to SRF and in particular to its transcriptional activation domain. The
      binding of ATF6 to SRF was also detected in vitro. An ATF6-VP16 chimera activated
      expression of an SRE reporter gene in HeLa cells, suggesting that ATF6 can
      interact with endogenous SRF. More strikingly, an antisense ATF6 construct
      reduced serum induction of a c-fos reporter gene, suggesting that ATF6 is
      involved in activation of transcription by SRF. ATF6 was previously partially
      cloned as a member of the ATF family. The complete cDNA of ATF6 was isolated, and
      its expression pattern was described.

PMID- 9271375
TI  - Identification of putative c-Myc-responsive genes: characterization of rcl, a
      novel growth-related gene.
AB  - The c-Myc protein is a helix-loop-helix leucine zipper oncogenic transcription
      factor that participates in the regulation of cell proliferation,
      differentiation, and apoptosis. The biochemical function of c-Myc has been well
      described, yet the identities of downstream effectors are just beginning to
      emerge. We describe the identification of a set of c-Myc-responsive genes in the
      Rat1a fibroblast through the application of cDNA representational difference
      analysis (RDA) to cDNAs isolated from nonadherent Rat1a and Rat1a-myc cells. In
      this system, c-Myc overexpression is sufficient to induce the transformed
      phenotype of anchorage-independent growth. We identified 20 differentially
      expressed cDNAs, several of which represent novel cDNA sequences. We further
      characterized one of the novel cDNAs identified in this screen, termed rcl. rcl
      expression is (i) directly stimulated by c-Myc; (ii) stimulated in the in vivo
      growth system of regenerating rat liver, as is c-myc; and (iii) elevated in human
      lymphoid cells that overexpress c-myc. By using an anti-Rcl antibody, immunoblot
      analysis, and immunofluorescence microscopy, the Rcl protein was found to be a 23
      kDa nuclear protein. Ectopic expression of the protein encoded by the rcl cDNA
      induces anchorage-independent growth in Rat1a fibroblasts, albeit to a diminished
      extent compared to ectopic c-Myc expression. These data suggest a role for rcl
      during cellular proliferation and c-Myc-mediated transformation.

PMID- 9271376
TI  - Inactivation of pRB-related proteins p130 and p107 mediated by the J domain of
      simian virus 40 large T antigen.
AB  - Inactivation of the retinoblastoma tumor suppressor protein (pRB) contributes to
      tumorigenesis in a wide variety of cancers. In contrast, the role of the two pRB
      related proteins, p130 and p107, in oncogenic transformation is unclear. The
      LXCXE domain of simian virus 40 large T antigen (TAg) specifically binds to pRB,
      p107, and p130. We have previously shown that the N terminus and the LXCXE domain
      of TAg cooperate to alter the phosphorylation state of p130 and p107. Here, we
      demonstrate that TAg promotes the degradation of p130 and that the N terminus of
      TAg is required for this activity. The N terminus of TAg has homology to the J
      domain of the DnaJ family of molecular chaperone proteins. Mutants with mutations
      in the J-domain homology region of TAg are defective for altering p130 and p107
      phosphorylation and for p130 degradation. A heterologous J-domain from a human
      DnaJ protein can functionally substitute for the N terminus of TAg in the effect
      on p107 and p130 phosphorylation and p130 stability. We further demonstrate that
      the J-domain homology region of TAg confers a growth advantage to wild-type mouse
      embryo fibroblasts (MEFs) but is dispensable in the case of MEFs lacking both
      p130 and p107. This indicates that p107 and p130 have overlapping growth
      suppressing activities whose inactivation is mediated by the J domain of TAg.

PMID- 9271377
TI  - Control of thrombopoietin-induced megakaryocytic differentiation by the mitogen
      activated protein kinase pathway.
AB  - Thrombopoietin (TPO) is the major regulator of both growth and differentiation of
      megakaryocytes. We previously showed that both functions can be generated by TPO
      in the megakaryoblastic cell line UT7, in which murine Mpl was introduced, and
      are independently controlled by distinct regions of the cytoplasmic domain of
      Mpl. Particularly, residues 71 to 94 of this domain (deleted in the mutant mpl
      delta3) were found to be required for megakaryocytic maturation but dispensable
      for proliferation. We show here that TPO-induced differentiation in UT7 cells is
      tightly dependent on a strong, long-lasting activation of the mitogen-activated
      protein kinase (MAPK) pathway. Indeed, (i) in UT7-mpl cells, TPO induced a strong
      activation of extracellular signal-regulated kinases (ERK) which was persistent
      until at least 4 days in TPO-containing medium; (ii) a specific MAPK kinase (MEK)
      inhibitor inhibited TPO-induced megakaryocytic gene expression; (iii) the Mpl
      mutant mpl delta3, which displayed no maturation activity, transduced only a weak
      and transient ERK activation in UT7 cells; and (iv) TPO-induced megakaryocytic
      differentiation in UT7-mpl delta3 cells was partially restored by expression of a
      constitutively activated mutant of MEK. The capacity of TPO to trigger a strong
      and prolonged MAPK signal depended on the cell in which Mpl was introduced. In
      BAF3-mpl cells, TPO triggered a weak and transient ERK activation, similar to
      that induced in UT7-mpl delta3 cells. In these cells, no difference in MAPK
      activation was found between normal Mpl and mpl delta3. Thus, depending on the
      cellular context, several distinct regions of the cytoplasmic domain of Mpl and
      signaling pathways may contribute to generate quantitative variations in MAPK
      activation.

PMID- 9271378
TI  - Saccharomyces cerevisiae Nip7p is required for efficient 60S ribosome subunit
      biogenesis.
AB  - The Saccharomyces cerevisiae temperature-sensitive (ts) allele nip7-1 exhibits
      phenotypes associated with defects in the translation apparatus, including
      hypersensitivity to paromomycin and accumulation of halfmer polysomes. The cloned
      NIP7+ gene complemented the nip7-1 ts growth defect, the paromomycin
      hypersensitivity, and the halfmer defect. NIP7 encodes a 181-amino-acid protein
      (21 kDa) with homology to predicted products of open reading frames from humans,
      Caenorhabditis elegans, and Arabidopsis thaliana, indicating that Nip7p function
      is evolutionarily conserved. Gene disruption analysis demonstrated that NIP7 is
      essential for growth. A fraction of Nip7p cosedimented through sucrose gradients
      with free 60S ribosomal subunits but not with 80S monosomes or polysomal
      ribosomes, indicating that it is not a ribosomal protein. Nip7p was found evenly
      distributed throughout the cytoplasm and nucleus by indirect immunofluorescence;
      however, in vivo localization of a Nip7p-green fluorescent protein fusion protein
      revealed that a significant amount of Nip7p is present inside the nucleus, most
      probably in the nucleolus. Depletion of Nip7-1p resulted in a decrease in protein
      synthesis rates, accumulation of halfmers, reduced levels of 60S subunits, and,
      ultimately, cessation of growth. Nip7-1p-depleted cells showed defective pre-rRNA
      processing, including accumulation of the 35S rRNA precursor, presence of a 23S
      aberrant precursor, decreased 20S pre-rRNA levels, and accumulation of 27S pre
      rRNA. Delayed processing of 27S pre-rRNA appeared to be the cause of reduced
      synthesis of 25S rRNA relative to 18S rRNA, which may be responsible for the
      deficit of 60S subunits in these cells.

PMID- 9271379
TI  - Nijmegen breakage syndrome cells fail to induce the p53-mediated DNA damage
      response following exposure to ionizing radiation.
AB  - The functionality of the p53-mediated pathway, activated in response to DNA
      damage, has been assessed in primary fibroblast cell cultures and Epstein-Barr
      virus-transformed lymphoblastoid cell lines derived from Nijmegen breakage
      syndrome (NBS) patients. This autosomal recessive disease is characterized by
      microcephaly, growth and mental retardation, chromosomal instability,
      radiosensitivity, and high cancer incidence. The recent mapping of the NBS gene
      to chromosome 8q21 demonstrates that NBS is genetically distinct from ataxia
      telangiectasia (AT). Changes in p53 protein levels were significantly reduced and
      delayed in all the NBS fibroblast cell cultures and lymphoblastoid cell lines
      examined compared to normal cultures over a 4-h period postirradiation (5 Gy).
      The transcriptional activation of p21(WAF1/CIP1) mRNA was also lower in 12 NBS
      fibroblast cultures examined. In agreement with an abrogated p53 function, NBS
      cells exposed to ionizing radiation show an abnormal cell cycle arrest at G1-S
      and a prolonged accumulation of cells in the G2 phase. In contrast, exposure to
      the alkylating agent methyl methanesulfonate results in similar increases of p53
      and p21(WAF1/CIP1) mRNA in both cell types. The ATM gene transcript was found to
      be expressed at similar levels in NBS and normal cells, whereas it was strongly
      reduced in the AT homozygote cells examined. These results suggest that the ATM
      gene product cannot substitute for that of the NBS gene in the signaling of
      cellular damage produced by ionizing radiation and that both are involved in the
      activation of p53. The suboptimal p53-mediated response could contribute to the
      high cancer risk and radiosensitivity seen in NBS patients.

PMID- 9271380
TI  - Functional analysis of Rrp7p, an essential yeast protein involved in pre-rRNA
      processing and ribosome assembly.
AB  - During the functional analysis of open reading frames (ORFs) identified during
      the sequencing of chromosome III of Saccharomyces cerevisiae, the previously
      uncharacterized ORF YCL031C (now designated RRP7) was deleted. RRP7 is essential
      for cell viability, and a conditional null allele was therefore constructed, by
      placing its expression under the control of a regulated GAL promoter. Genetic
      depletion of Rrp7p inhibited the pre-rRNA processing steps that lead to the
      production of the 20S pre-rRNA, resulting in reduced synthesis of the 18S rRNA
      and a reduced ratio of 40S to 60S ribosomal subunits. A screen for multicopy
      suppressors of the lethality of the GAL::rrp7 allele isolated the two genes
      encoding a previously unidentified ribosomal protein (r-protein) that is highly
      homologous to the rat r-protein S27. When present in multiple copies, either gene
      can suppress the lethality of an RRP7 deletion mutation and can partially restore
      the ribosomal subunit ratio in Rrp7p-depleted cells. Deletion of both r-protein
      genes is lethal; deletion of either single gene has an effect on pre-rRNA
      processing similar to that of Rrp7p depletion. We believe that Rrp7p is required
      for correct assembly of rpS27 into the preribosomal particle, with the inhibition
      of pre-rRNA processing appearing as a consequence of this defect.

PMID- 9271382
TI  - Zap1p, a metalloregulatory protein involved in zinc-responsive transcriptional
      regulation in Saccharomyces cerevisiae.
AB  - Zinc ion homeostasis in Saccharomyces cerevisiae is controlled primarily through
      the transcriptional regulation of zinc uptake systems in response to
      intracellular zinc levels. A high-affinity uptake system is encoded by the ZRT1
      gene, and its expression is induced more than 30-fold in zinc-limited cells. A
      low-affinity transporter is encoded by the ZRT2 gene, and this system is also
      regulated by zinc. We used a genetic approach to isolate mutants whose ZRT1
      expression is no longer repressed in zinc-replete cells, and a new gene, ZAP1,
      was identified. ZAP1 encodes a 93-kDa protein with sequence similarity to
      transcriptional activators; the C-terminal 174 amino acids contains five C2H2
      zinc finger domains, and the N terminus (residues 1 to 706) has two potential
      acidic activation domains. The N-terminal region also contains 12% histidine and
      cysteine residues. The mutant allele isolated, ZAP1-1up, is semidominant and
      caused high-level expression of ZRT1 and ZRT2 in both zinc-limited and zinc
      replete cells. This phenotype is the result of a mutation that substitutes a
      serine for a cysteine residue in the N-terminal region. A zap1 deletion mutant
      grew well on zinc-replete media but poorly on zinc-limiting media. This mutant
      had low-level ZRT1 and ZRT2 expression in zinc-limited as well as zinc-replete
      cells. These data indicate that Zap1p plays a central role in zinc ion
      homeostasis by regulating transcription of the zinc uptake system genes in
      response to zinc. Finally, we present evidence that Zap1p regulates transcription
      of its own promoter in response to zinc through a positive autoregulatory
      mechanism.

PMID- 9271381
TI  - Identification of mouse histone deacetylase 1 as a growth factor-inducible gene.
AB  - Reversible acetylation of core histones plays an important role in
      transcriptional regulation, cell cycle progression, and developmental events. The
      acetylation state of histones is controlled by the activities of acetylating and
      deacetylating enzymes. By using differential mRNA display, we have identified a
      mouse histone deacetylase gene, HD1, as an interleukin-2-inducible gene in murine
      T cells. Sequence alignments revealed that murine HD1 is highly homologous to the
      yeast RPD3 pleiotropic transcriptional regulator. Indirect immunofluorescence
      microscopy proved that mouse HD1 is a nuclear protein. When expressed in yeast,
      murine HD1 was also detected in the nucleus, although it failed to complement the
      rpd3delta deletion phenotype. HD1 mRNA expression was low in G0 mouse cells but
      increased when the cells crossed the G1/S boundary after growth stimulation.
      Immunoprecipitation experiments and functional in vitro assays showed that HD1
      protein is associated with histone deacetylase activity. Both HD1 protein levels
      and total histone deacetylase activity increased upon interleukin-2 stimulation
      of resting B6.1 cells. When coexpressed with a luciferase reporter construct, HD1
      acted as a negative regulator of the Rous sarcoma virus enhancer/promoter. HD1
      overexpression in stably transfected Swiss 3T3 cells caused a severe delay during
      the G2/M phases of the cell cycle. Our results indicate that balanced histone
      acetylation/deacetylation is crucial for normal cell cycle progression of
      mammalian cells.

PMID- 9271383
TI  - The nuclear orphan receptors COUP-TF and ARP-1 positively regulate the trout
      estrogen receptor gene through enhancing autoregulation.
AB  - The rainbow trout estrogen receptor (rtER) is a positively autoregulated gene in
      liver cells. In a previous report, we showed that upregulation is mediated by an
      estrogen response element (ERE) located in the proximal promoter of the gene and
      that a half binding site for nuclear receptors (5'-TGACCT-3') located 15 bp
      upstream of the ERE is involved in the magnitude of the estrogen response. We now
      report that the human orphan receptor COUP-TF and a COUP-TF-like protein from
      trout liver are able to bind to the consensus half-site. When cotransfected with
      the rtER gene proximal promoter, COUP-TF had no regulatory functions on its own.
      Interestingly, COUP-TF enhanced rtER transactivation properties in the presence
      of estradiol in a dose-dependent manner when cotransfected with the rtER gene
      promoter. Unliganded retinoid receptor heterodimers had the same helper function
      as COUP-TF in the presence of estradiol but were switched to repressors when the
      ligand all-trans-retinoic acid was added. Mutation of the consensus half-site
      only slightly reduced COUP-TF helper function, suggesting that it actually
      results from a complex mechanism that probably involves both DNA binding of COUP
      TF to the promoter and protein-protein interaction with another transcription
      factor bound to the promoter. Nevertheless, a DNA-binding-defective mutant of
      COUP-TF was also defective in ER helper function. Competition footprinting
      analysis suggested that COUP-TF actually establishes contacts with the consensus
      upstream half-site and the downstream ERE half-site that would form a DR-24-like
      response element. Interaction of COUP-TF with the DR-24 element was confirmed in
      footprinting assays by using nuclear extracts from Saccharomyces cerevisiae
      expressing COUP-TF. Finally, interaction of COUP-TF with mutants of the rtER gene
      promoter showed that COUP-TF recognizes the ERE when the upstream half-site is
      mutated. These data show that COUP-TF may activate transcription through
      interaction with other nuclear receptors. This cross-talk between liganded
      nuclear receptors and orphan receptors is likely to modulate the spectrum of
      action of a particular ligand-receptor complex and may participate in the cell
      type specificity of the ligand effect.

PMID- 9271384
TI  - Cla4p, a Saccharomyces cerevisiae Cdc42p-activated kinase involved in
      cytokinesis, is activated at mitosis.
AB  - Yeasts have three functionally redundant G1 cyclins required for cell cycle
      progression through G1. Mutations in GIN4 and CLA4 were isolated in a screen for
      mutants that are inviable with deletions in the G1 cyclins CLN1 and CLN2. cln1
      cln2 cla4 and cln1 cln2 gin4 cells arrest with a cytokinesis defect; this defect
      was efficiently rescued by CLN1 or CLN2 expression. GIN4 encodes a protein with
      strong homology to the Snflp serine/threonine kinase. Cla4p is homologous to
      mammalian p21-activated kinases (PAKs) (kinases activated by the rho-class GTPase
      Rac or Cdc42). We developed a kinase assay for Cla4p. Cla4p kinase was activated
      in vivo by the GTP-bound form of Cdc42p. The specific activity of Cla4p was cell
      cycle regulated, peaking near mitosis. Deletion of the Cla4p pleckstrin domain
      diminished kinase activity nearly threefold and eliminated in vivo activity.
      Deletion of the Cla4p Cdc42-binding domain increased kinase activity nearly
      threefold, but the mutant only weakly rescued cla4 function in vivo. This
      suggests that kinase activity alone is not sufficient for full function in vivo.
      Deletion of the Cdc42-binding domain also altered the cell cycle regulation of
      kinase activity. Instead of peaking at mitosis, the mutant kinase activity
      exhibited reduced cell cycle regulation and peaked at the G1/S border. Cla4p
      kinase activity was not reduced by mutational inactivation of gin4, suggesting
      that Gin4p may be downstream or parallel to Cla4p in the regulation of
      cytokinesis.

PMID- 9271385
TI  - RRB1 and RRB2 encode maize retinoblastoma-related proteins that interact with a
      plant D-type cyclin and geminivirus replication protein.
AB  - Unlike mammalian and yeast cells, little is known about how plants regulate G1
      progression and entry into the S phase of the cell cycle. In mammalian cells, a
      key regulator of this process is the retinoblastoma tumor suppressor protein
      (RB). In contrast, G1 control in Saccharomyces cerevisiae does not utilize an RB
      like protein. We report here the cloning of cDNAs from two Zea mays genes, RRB1
      and RRB2, that encode RB-related proteins. Further, RRB2 transcripts are
      alternatively spliced to yield two proteins with different C termini. At least
      one RRB gene is expressed in all the tissues examined, with the highest levels
      seen in the shoot apex. RRB1 is a 96-kDa nuclear protein that can physically
      interact with two mammalian DNA tumor virus oncoproteins, simian virus 40 large-T
      antigen and adenovirus E1A, and with a plant D-type cyclin. These associations
      are abolished by mutation of a conserved cysteine residue in RRB1 that is also
      essential for RB function. RRB1 binding potential is also sensitive to deletions
      in the conserved A and B domains, although differences exist in these effects
      compared to those of human RB. RRB1 can also bind to the AL1 protein from tomato
      golden mosaic virus (TGMV), a protein which is essential for TGMV DNA
      replication. These results suggest that G1 regulation in plant cells is
      controlled by a mechanism which is much more similar to that found in mammalian
      cells than that in yeast.

PMID- 9271386
TI  - Ran-binding protein 5 (RanBP5) is related to the nuclear transport factor
      importin-beta but interacts differently with RanBP1.
AB  - We report the identification and characterization of a novel 124-kDa Ran binding
      protein, RanBP5. This protein is related to importin-beta, the key mediator of
      nuclear localization signal (NLS)-dependent nuclear transport. RanBP5 was
      identified by two independent methods: it was isolated from HeLa cells by using
      its interaction with RanGTP in an overlay assay to monitor enrichment, and it was
      also found by the yeast two-hybrid selection method with RanBP1 as bait. RanBP5
      binds to RanBP1 as part of a trimeric RanBP1-Ran-RanBP5 complex. Like importin
      beta, RanBP5 strongly binds the GTP-bound form of Ran, stabilizing it against
      both intrinsic and RanGAP1-induced GTP hydrolysis and also against nucleotide
      exchange. The GAP resistance of the RanBP5-RanGTP complex can be relieved by
      RanBP1, which might reflect an in vivo role for RanBP1. RanBP5 is a predominantly
      cytoplasmic protein that can bind to nuclear pore complexes. We propose that
      RanBP5 is a mediator of a nucleocytoplasmic transport pathway that is distinct
      from the importin-alpha-dependent import of proteins with a classical NLS.

PMID- 9271387
TI  - Identification of tumor-specific paclitaxel (Taxol)-responsive regulatory
      elements in the interleukin-8 promoter.
AB  - Paclitaxel (Taxol) is a novel chemotherapeutic drug that is effective against
      breast and ovarian cancers. Although the primary target of paclitaxel is
      microtubules, its efficacy exceeds that of conventional microtubule-disrupting
      agents, suggesting that it may have additional cellular effects. Previously, we
      demonstrated that paclitaxel can induce interleukin-8 (IL-8) gene expression at
      the transcriptional level in subsets of human ovarian cancer lines. In this as
      well as the previous report, we present evidence that this ability is not linked
      to the lipopolysaccharide pathway of IL-8 gene induction. The present study
      identifies the cis-acting elements and trans-acting factors involved in this
      induction by transfecting DNA constructs containing the 5'-flanking region of the
      IL-8 gene linked to the chloramphenicol acetyltransferase reporter gene into
      paclitaxel-responsive and nonresponsive ovarian cancer cells (responsiveness
      refers to the IL-8 response). Paclitaxel only activated the IL-8 promoter in
      responsive cells. The AP-1 and NF-kappaB binding sites in the IL-8 promoter are
      required for activation by paclitaxel; in contrast, a C/EBP site required for IL
      8 promoter activation in other cell types is not involved. Gel shift assays
      demonstrate that paclitaxel causes a marked increase in protein binding to the NF
      kappaB and AP-1 consensus binding sequences in the paclitaxel-responsive ovarian
      cells, but not the nonresponsive cells. The induction of NF-kappaB and AP-1
      binding is reduced by the addition of protein kinase C inhibitors and cyclic AMP
      effector, respectively. These results demonstrate a molecular mechanism for cell
      specific paclitaxel-induced IL-8 gene expression which may have clinical
      relevance.

PMID- 9271389
TI  - Luman, a new member of the CREB/ATF family, binds to herpes simplex virus VP16
      associated host cellular factor.
AB  - The human host cell factor (HCF) is expressed in a variety of adult and fetal
      tissues, and its gene is conserved in animals as diverse as mammals and insects.
      However, its only known function is to stabilize the herpes simplex virus virion
      transactivator VP16 in a complex with the cellular POU domain protein Oct-1 and
      cis-acting regulatory elements in promoters of immediate-early viral genes. To
      identify a cellular function for HCF, we used the yeast two-hybrid system to
      identify a cellular ligand for HCF. This protein, Luman, appears to be a cyclic
      AMP response element (CRE)-binding protein/activating transcription factor 1
      protein of the basic leucine zipper superfamily. It binds CREs in vitro and
      activates CRE-containing promoters when transfected into COS7 cells. This
      activation of transcription was synergistically enhanced by the presence of
      CCAAT/enhancer-binding protein elements and inhibited by AP-1 elements in the
      promoter. In addition to a basic DNA binding domain, Luman possesses an unusually
      long leucine zipper and an acidic amino-terminal activation domain. These
      features in Luman are also present in what appear to be homologs in the mouse,
      Drosophila melanogaster, and Caenorhabditis elegans. Luman and VP16 appear to
      have similar mechanisms for binding HCF, as in vitro each competitively inhibited
      the binding of the other to HCF. In transfected cells, however, while VP16
      strongly inhibited the ability of GAL-Luman to activate transcription from a GAL4
      upstream activation sequence-containing promoter, Luman was unable to inhibit the
      activity of GAL-VP16. Luman appears to be a ubiquitous transcription factor, and
      its mRNA was detected in all human adult and fetal tissues examined. The possible
      role of HCF in regulating the function of this ubiquitous transcription factor is
      discussed.

PMID- 9271388
TI  - Multiple interdependent sequence elements control splicing of a fibroblast growth
      factor receptor 2 alternative exon.
AB  - The fibroblast growth factor receptor 2 gene contains a pair of mutually
      exclusive alternative exons, one of which (K-SAM) is spliced specifically in
      epithelial cells. We have described previously (F. Del Gatto and R. Breathnach,
      Mol. Cell. Biol. 15:4825-4834, 1995) some elements controlling K-SAM exon
      splicing, namely weak exon splice sites, an exon-repressing sequence, and an
      intron-activating sequence. We identify here two additional sequences in the
      intron downstream from the K-SAM exon which activate splicing of the exon. The
      first sequence (intron-activating sequence 2 [IAS2]) lies 168 to 186 nucleotides
      downstream from the exon's 5' splice site. The second sequence (intron-activating
      sequence 3 [IAS3]) lies 933 to 1,052 nucleotides downstream from the exon's 5'
      splice site. IAS3 is a complex region composed of several parts, one of which
      (nucleotides 963 to 983) can potentially form an RNA secondary structure with
      IAS2. This structure is composed of two stems separated by an asymmetric bulge.
      Mutations which disrupt either stem decrease activation, while compensatory
      mutations which reestablish the stem restore activation, either completely or
      partially, depending on the mutation. We present a model for K-SAM exon splicing
      involving the intervention of multiple, interdependent pre-mRNA sequence
      elements.

PMID- 9271390
TI  - Core binding factor cannot synergistically activate the myeloperoxidase proximal
      enhancer in immature myeloid cells without c-Myb.
AB  - The myeloperoxidase (MPO) gene is transcribed specifically in immature myeloid
      cells and is regulated in part by a 414-bp proximal enhancer. Mutation of a core
      binding factor (CBF)-binding site at -288 decreased enhancer activity 30-fold in
      32D cl3 myeloid cells cultured in granulocyte colony-stimulating factor (G-CSF).
      A novel functional analysis, linking the CBF-binding site to an enhancer deletion
      series, located at -147 an evolutionarily conserved c-Myb-binding site which was
      required for optimal enhancer activity and synergy with CBF in 32D cells. These
      sites cooperated in isolation and independent of a precise spacing. Deletional
      analysis carried out in the absence of the c-Myb-binding site at -147 located at 
      301 a second c-Myb-binding site which also synergized with CBF to activate the
      enhancer. A GA-rich region at -162 contributed to cooperation with CBF when the
      adjacent c-Myb-binding site was intact. Mutation of both c-Myb-binding sites in
      the context of the entire enhancer greatly impaired activation by endogenous CBF
      in 32D cells. Similarly, activation by c-Myb was impaired in constructs lacking
      the CBF-binding site. CBF and c-Myb were required for induction of MPO proximal
      enhancer activity when 32D cells differentiated in response to G-CSF. A fusion
      protein containing the Gal4 DNA-binding domain and the AML-1B activation domain,
      amino acids 216 to 480, activated transcription alone and cooperatively with c
      Myb in nonmyeloid CV-1 cells. Determining how CBF and c-Myb synergize in myeloid
      cells might contribute to our understanding of leukemogenesis by the AML1-ETO,
      AML1-MDS1, CBFbeta-SMMHC, and v-Myb oncoproteins.

PMID- 9271391
TI  - Qsr1p, a 60S ribosomal subunit protein, is required for joining of 40S and 60S
      subunits.
AB  - QSR1 is a recently discovered, essential Saccharomyces cerevisiae gene, which
      encodes a 60S ribosomal subunit protein. Thirty-one unique temperature-sensitive
      alleles of QSR1 were generated by regional codon randomization within a conserved
      20-amino-acid sequence of the QSR1-encoded protein. The temperature-sensitive
      mutants arrest as viable, large, unbudded cells 24 to 48 h after a shift to 37
      degrees C. Polysome and ribosomal subunit analysis by velocity gradient
      centrifugation of lysates from temperature-sensitive qsr1 mutants and from cells
      in which Qsr1p was depleted by down regulation of an inducible promoter revealed
      the presence of half-mer polysomes and a large pool of free 60S subunits that
      lack Qsr1p. In vitro subunit-joining assays and analysis of a mutant conditional
      for the synthesis of Qsr1p demonstrate that 60S subunits devoid of Qsr1p are
      unable to join with 40S subunits whereas 60S subunits that contain either wild
      type or mutant forms of the protein are capable of subunit joining. The defective
      60S subunits result from a reduced association of mutant Qsr1p with 60S subunits.
      These results indicate that Qsr1p is required for ribosomal subunit joining.

PMID- 9271392
TI  - SQT1, which encodes an essential WD domain protein of Saccharomyces cerevisiae,
      suppresses dominant-negative mutations of the ribosomal protein gene QSR1.
AB  - QSR1 is an essential Saccharomyces cerevisiae gene, which encodes a 60S ribosomal
      subunit protein required for joining of 40S and 60S subunits. Truncations of QSR1
      predicted to encode C-terminally truncated forms of Qsr1p do not substitute for
      QSR1 but do act as dominant negative mutations, inhibiting the growth of yeast
      when expressed from an inducible promoter. The dominant negative mutants exhibit
      a polysome profile characterized by 'half-mer' polysomes, indicative of a subunit
      joining defect like that seen in other qsr1 mutants (D. P. Eisinger, F. A. Dick,
      and B. L. Trumpower, Mol. Cell. Biol. 17:5136-5145, 1997.) By screening a high
      copy yeast genomic library, we isolated several clones containing overlapping
      inserts of a novel gene that rescues the slow-growth phenotype of the dominant
      negative qsr1 truncations. The suppressor of qsr1 truncation mutants, SQT1, is an
      essential gene, which encodes a 47.1-kDa protein containing multiple WD repeats
      and which interacts strongly with Qsr1p in a yeast two-hybrid system. SQT1
      restores growth and the "half-mer" polysome profile of the dominant negative qsr1
      mutants to normal, but it does not rescue temperature-sensitive qsr1 mutants or
      the original qsr1-1 missense allele. In yeast cell lysates, Sqt1p fractionates as
      part of an oligomeric protein complex that is loosely associated with ribosomes
      but is distinct from known eukaryotic initiation factor complexes. Loss of SQT1
      function by down regulation from an inducible promoter results in formation of
      half-mer polyribosomes and decreased Qsr1p levels on free 60S subunits. Sqt1p
      thus appears to be involved in a late step of 60S subunit assembly or
      modification in the cytoplasm.

PMID- 9271394
TI  - Characterization of the maize Mutator transposable element MURA transposase as a
      DNA-binding protein.
AB  - The autonomous MuDR element of the Mutator (Mu) transposable element family of
      maize encodes at least two proteins, MURA and MURB. Based on amino acid sequence
      similarity, previous studies have reported that MURA is likely to be a
      transposase. The functional characterization of MURA has been hindered by the
      instability of its cDNA, mudrA, in Escherichia coli. In this study, we report the
      first successful stabilization and expression of MURA in Saccharomyces
      cerevisiae. Gel mobility shift assays demonstrate that MURA is a DNA-binding
      protein that specifically binds to sequences within the highly conserved Mu
      element terminal inverted repeats (TIRs). DNase I and 1,10-phenanthroline-copper
      footprinting of MURA-Mu1 TIR complexes indicate that MURA binds to a conserved
      approximately 32-bp region in the TIR of Mu1. In addition, MURA can bind to the
      same region in the TIRs of all tested actively transposing Mu elements but binds
      poorly to the diverged Mu TIRs of inactive elements. Previous studies have
      reported a correlation between Mu transposon inactivation and methylation of the
      Mu element TIRs. Gel mobility shift assays demonstrate that MURA can interact
      differentially with unmethylated, hemimethylated, and homomethylated TIR
      substrates. The significance of MURA's interaction with the TIRs of Mu elements
      is discussed in the context of what is known about the regulation and mechanisms
      of Mutator activities in maize.

PMID- 9271393
TI  - Anchoring of CREB binding protein to the human T-cell leukemia virus type 1
      promoter: a molecular mechanism of Tax transactivation.
AB  - The human T-cell leukemia virus type 1 (HTLV-1)-encoded Tax protein activates
      viral transcription through interaction with the cellular transcription factor
      CREB (cyclic AMP response element [CRE] binding protein). Although Tax stabilizes
      the binding of CREB to the Tax-responsive viral CREs in the HTLV-1 promoter, the
      precise molecular mechanism by which Tax mediates strong transcriptional
      activation through CREB remains unclear. In this report, we show that Tax
      promotes high-affinity binding of the KIX domain of CREB binding protein (CBP) to
      CREB-viral CRE complexes, increasing the stability of KIX in these nucleoprotein
      complexes by up to 4.4 kcal/mol. Comparable KIX binding affinities were measured
      for both phosphorylated and unphosphorylated forms of CREB, and in all cases high
      affinity binding was dependent upon both Tax and the viral CRE. Tax also promoted
      association of KIX to a truncated form of CREB containing only the 73-amino-acid
      basic leucine zipper (bZIP) domain, indicating that the entire amino-terminal CBP
      interacting domain of CREB is nonessential in the presence of Tax. Functional
      studies upheld the binding studies, as expression of the bZIP domain of CREB was
      sufficient to support Tax transactivation of HTLV-1 transcription in vivo.
      Finally, we show that transfection of a KIX expression plasmid, which lacks
      activation properties, inhibited Tax transactivation in vivo. This suggests that
      KIX occupies the CBP binding site on Tax, and therefore CBP is likely a cofactor
      in mediating Tax stimulation of HTLV-1 transcription. Together, these data
      support a model in which Tax anchors CBP to the HTLV-1 promoter, with strong
      transcriptional activation resulting from the CBP-associated activities of
      nucleosome remodeling and recruitment of the general transcription machinery.

PMID- 9271395
TI  - Chromosome end elongation by recombination in the mosquito Anopheles gambiae.
AB  - One of the functions of telomeres is to counteract the terminal nucleotide loss
      associated with DNA replication. While the vast majority of eukaryotic organisms
      maintain their chromosome ends via telomerase, an enzyme system that generates
      short, tandem repeats on the ends of chromosomes, other mechanisms such as the
      transposition of retrotransposons or recombination can also be used in some
      species. Chromosome end regression and extension were studied in a medically
      important mosquito, the malaria vector Anopheles gambiae, to determine how this
      dipteran insect maintains its chromosome ends. The insertion of a transgenic
      pUChsneo plasmid at the left end of chromosome 2 provided a unique marker for
      measuring the dynamics of the 2L telomere over a period of about 3 years. The
      terminal length was relatively uniform in the 1993 population with the
      chromosomes ending within the white gene sequence of the inserted transgene.
      Cloned terminal chromosome fragments did not end in short repeat sequences that
      could have been synthesized by telomerase. By late 1995, the chromosome ends had
      become heterogeneous: some had further shortened while other chromosomes had been
      elongated by regenerating part of the integrated pUChsneo plasmid. A model is
      presented for extension of the 2L chromosome by recombination between homologous
      2L chromosome ends by using the partial plasmid duplication generated during its
      original integration. It is postulated that this mechanism is also important in
      wild-type telomere elongation.

PMID- 9271396
TI  - Requirement of protein kinase C zeta for stimulation of protein synthesis by
      insulin.
AB  - The ability of insulin to stimulate protein synthesis and cellular growth is
      mediated through the insulin receptor (IR), which phosphorylates Tyr residues in
      the insulin receptor substrate-signaling proteins (IRS-1 and IRS-2), Gab-1, and
      Shc. These phosphorylated substrates directly bind and activate enzymes such as
      phosphatidylinositol 3'-kinase (PI3K) and the guanine nucleotide exchange factor
      for p21Ras (GRB-2/SOS), which are in turn required for insulin-stimulated protein
      synthesis, cell cycle progression, and prevention of apoptosis. We have now shown
      that one or more members of the atypical protein kinase C group, as exemplified
      by the zeta isoform (PKC zeta), are downstream of IRS-1 and P13K and mediate the
      effect of insulin on general protein synthesis. Ectopic expression of
      constitutively activated PKC zeta eliminates the requirement of IRS-1 for general
      protein synthesis but not for insulin-stimulated activation of 70-kDa S6 kinase
      (p70S6K), synthesis of growth-regulated proteins (e.g., c-Myc), or mitogenesis.
      The fact that PKC zeta stimulates general protein synthesis but not activation of
      p70S6K indicates that PKC zeta activation does not involve the proto-oncogene
      Akt, which is also activated by PI3K. Yet insulin is still required for the
      stimulation of general protein synthesis in the presence of constitutively active
      PKC zeta and in the absence of IRS-1, suggesting a requirement for the
      convergence of the IRS-1/PI3K/PKC zeta pathway with one or more additional
      pathways emanating from the IR, e.g., Shc/SOS/p21Ras/mitogen-activated protein
      kinase. Thus, PI3K appears to represent a bifurcation in the insulin signaling
      pathway, one branch leading through PKC zeta to general protein synthesis and
      one, through Akt and the target of rapamycin (mTOR), to growth-regulated protein
      synthesis and cell cycle progression.

PMID- 9271397
TI  - Promoter selective transcriptional synergy mediated by sterol regulatory element
      binding protein and Sp1: a critical role for the Btd domain of Sp1.
AB  - Cellular cholesterol and fatty acid levels are coordinately regulated by a family
      of transcriptional regulatory proteins designated sterol regulatory element
      binding proteins (SREBPs). SREBP-dependent transcriptional activation from all
      promoters examined thus far is dependent on the presence of an additional binding
      site for a ubiquitous coactivator. In the low-density lipoprotein (LDL) receptor,
      acetyl coenzyme A carboxylase (ACC), and fatty acid synthase (FAS) promoters,
      which are all regulated by SREBP, the coactivator is the transcription factor
      Sp1. In this report, we demonstrate that Sp3, another member of the Sp1 family,
      is capable of substituting for Sp1 in coactivating transcription from all three
      of these promoters. Results of an earlier study showed that efficient activation
      of transcription from the LDL receptor promoter required domain C of Sp1;
      however, this domain is not crucial for activation of the simian virus 40
      promoter, where synergistic activation occurs through multiple Sp1 binding sites
      and does not require SREBP. Also in the present report, we further localize the
      critical determinant of the C domain required for activation of the LDL receptor
      to a small region that is highly conserved between Sp1 and Sp3. This crucial
      domain encompasses the buttonhead box, which is a 10-amino-acid stretch that is
      present in several Sp1 family members, including the Drosophila buttonhead gene
      product. Interestingly, neither the buttonhead box nor the entire C domain is
      required for the activation of the FAS and ACC promoters even though both SREBP
      and Sp1 are critical players. ACC and FAS each contain two critical SREBP sites,
      whereas there is only one in the LDL receptor promoter. This finding suggested
      that buttonhead-dependent activation by SREBP and Sp1 may be limited to promoters
      that naturally contain a single SREBP recognition site. Consistent with this
      model, a synthetic construct containing three tandem copies of the native LDL
      receptor SREBP site linked to a single Sp1 site was also significantly activated
      in a buttonhead-independent fashion. Taken together, these studies indicate that
      transcriptional activation through the concerted action of SREBP and Sp1 can
      occur by at least two different mechanisms, and promoters that are activated by
      each one can potentially be identified by the number of critical SREBP binding
      sites that they contain.

PMID- 9271398
TI  - Posttranscriptional regulation of collagen alpha1(I) mRNA in hepatic stellate
      cells.
AB  - The hepatic stellate cell (HSC) is the primary cell responsible for the dramatic
      increase in the synthesis of type I collagen in the cirrhotic liver. Quiescent
      HSCs contain a low level of collagen alpha1(I) mRNA, while activated HSCs contain
      about 60- to 70-fold more of this mRNA. The transcription rate of the collagen
      alpha1(I) gene is only two fold higher in activated HSCs than in quiescent HSCs.
      In assays using actinomycin D or 5,6-dichlorobenzimidazole riboside collagen
      alpha1(I) mRNA has estimated half-lives of 1.5 h in quiescent HSCs and 24 h in
      activated HSCs. Thus, this 16-fold change in mRNA stability is primarily
      responsible for the increase in collagen alpha1(I) mRNA steady-state level in
      activated HSCs. We have identified a novel RNA-protein interaction targeted to
      the C-rich sequence in the collagen alpha1(I) mRNA 3' untranslated region (UTR).
      This sequence is localized 24 nucleotides 3' to the stop codon. In transient
      transfection experiments, mutation of this sequence diminished accumulation of an
      mRNA transcribed from a collagen alpha1(I) minigene and in stable transfections
      decreased the half-life of collagen alpha1(I) minigene mRNA. Binding to the
      collagen alpha1(I) 3' UTR is present in cytoplasmic extracts of activated but not
      quiescent HSCs. It contains as a subunit alphaCP, which is also found in the
      complex involved in stabilization of alpha-globin mRNA. The auxiliary factors
      necessary to promote binding of alphaCP to the collagen 3' UTR are distinct from
      the factors necessary for binding to the alpha-globin sequence. Since alphaCP is
      expressed in both quiescent and activated HSCs, these auxiliary factors are
      responsible for the differentially expressed RNA-protein interaction at the
      collagen alpha1(I) mRNA 3' UTR.

PMID- 9271399
TI  - Four distinct secretory pathways serve protein secretion, cell surface growth,
      and peroxisome biogenesis in the yeast Yarrowia lipolytica.
AB  - We have identified and characterized mutants of the yeast Yarrowia lipolytica
      that are deficient in protein secretion, in the ability to undergo dimorphic
      transition from the yeast to the mycelial form, and in peroxisome biogenesis.
      Mutations in the SEC238, SRP54, PEX1, PEX2, PEX6, and PEX9 genes affect protein
      secretion, prevent the exit of the precursor form of alkaline extracellular
      protease from the endoplasmic reticulum, and compromise peroxisome biogenesis.
      The mutants sec238A, srp54KO, pex2KO, pex6KO, and pex9KO are also deficient in
      the dimorphic transition from the yeast to the mycelial form and are affected in
      the export of only plasma membrane and cell wall-associated proteins specific for
      the mycelial form. Mutations in the SEC238, SRP54, PEX1, and PEX6 genes prevent
      or significantly delay the exit of two peroxisomal membrane proteins, Pex2p and
      Pex16p, from the endoplasmic reticulum en route to the peroxisomal membrane.
      Mutations in the PEX5, PEX16, and PEX17 genes, which have previously been shown
      to be essential for peroxisome biogenesis, affect the export of plasma membrane
      and cell wall-associated proteins specific for the mycelial form but do not
      impair exit from the endoplasmic reticulum of either Pex2p and Pex16p or of
      proteins destined for secretion. Biochemical analyses of these mutants provide
      evidence for the existence of four distinct secretory pathways that serve to
      deliver proteins for secretion, plasma membrane and cell wall synthesis during
      yeast and mycelial modes of growth, and peroxisome biogenesis. At least two of
      these secretory pathways, which are involved in the export of proteins to the
      external medium and in the delivery of proteins for assembly of the peroxisomal
      membrane, diverge at the level of the endoplasmic reticulum.

PMID- 9271400
TI  - Identification of positively and negatively acting elements regulating expression
      of the E2F2 gene in response to cell growth signals.
AB  - Mammalian cell growth is governed by regulatory activities that include the
      products of genes such as c-myc and ras that act early in G1, as well as the E2F
      family of transcription factors that accumulate later in G1 to regulate the
      expression of genes involved in DNA replication. Previous work has shown that the
      expression of the E2F1, E2F2, and E2F3 gene products is tightly regulated by cell
      growth. To further explore the mechanisms controlling accumulation of E2F
      activity, we have isolated genomic sequences flanking the 5' region of the E2F2
      coding sequence. Various assays demonstrate promoter activity in this sequence
      that reproduces the normal control of E2F2 expression during a growth
      stimulation. Sequence comparison reveals the presence of a variety of known
      transcription factor binding sites, including E-box elements that are consensus
      Myc binding sites, as well as E2F binding sites. We demonstrate that the E-box
      elements, which we show can function as Myc-responsive sites, contribute in a
      positive fashion to promoter function. We also find that E2F-dependent negative
      regulation in quiescent cells plays a significant role in the cell growth
      dependent control of the promoter, similar to the regulation of the E2F1 gene
      promoter.

PMID- 9271401
TI  - Transient expression of a winged-helix protein, MNF-beta, during myogenesis.
AB  - A novel winged-helix transcription factor, MNF-beta, is expressed coincidentally
      with cell cycle withdrawal and differentiation of skeletal myogenic cells. MNF
      beta is closely related to the myocyte nuclear factor (MNF) protein previously
      described (now termed MNF-alpha), but expression of the two isoforms is
      differentially regulated, and they exhibit distinctive functional properties with
      respect to DNA binding in vitro and transcriptional regulatory activity in
      transient-transfection assays. A DNA sequence motif binding MNF-beta with high
      affinity was selected from a library of random oligonucleotides and was found to
      be similar to but distinct from the cognate binding site for HNF-3beta, a more
      distantly related winged-helix protein. The temporal pattern of MNF-beta
      expression and the presence of MNF binding motifs within conserved promoter
      elements of several genes that modulate cell cycle progression support a working
      hypothesis that MNF proteins may modulate proliferation of myogenic precursor
      cells during development and muscle regeneration.

PMID- 9271402
TI  - Regulation of gene expression by cyclic GMP-dependent protein kinase requires
      nuclear translocation of the kinase: identification of a nuclear localization
      signal.
AB  - We recently demonstrated that cyclic GMP (cGMP)-dependent protein kinase (G
      kinase) activates the human fos promoter in a strictly cGMP-dependent manner (T.
      Gudi et al., J. Biol. Chem. 271:4597-4600, 1996). Here, we demonstrate that G
      kinase translocates to the nucleus by an active transport mechanism which
      requires a nuclear localization signal (NLS) and is regulated by cGMP.
      Immunofluorescent staining of G-kinase was predominantly cytoplasmic in untreated
      cells, but intense nuclear staining appeared in 8-bromo (Br)-cGMP-treated cells.
      We identified a putative NLS in the G-kinase ATP binding domain which resembles
      the NLS of the interleukin-1alpha precursor. Fusion of the G-kinase NLS to the N
      terminus of beta-galactosidase produced a chimeric protein which localized to the
      nucleus. Mutation of a single amino acid residue (K407-->E) within the G-kinase
      NLS produced an enzyme with normal cGMP-dependent activity in vitro which did not
      translocate to the nucleus and did not transactivate the fos promoter in the
      presence of 8-Br-cGMP in vivo. In contrast, N-terminally truncated versions of G
      kinase with constitutive, cGMP-independent activity in vitro localized to the
      nucleus and transactivated the fos promoter in the absence of 8-Br-cGMP. These
      results indicate that nuclear localization of G-kinase is required for
      transcriptional activation of the fos promoter and suggest that a conformational
      change of the kinase, induced by cGMP binding or by removal of the N-terminal
      autoinhibitory domain, functionally activates an otherwise cryptic NLS.

PMID- 9271403
TI  - Control of the translational efficiency of beta-F1-ATPase mRNA depends on the
      regulation of a protein that binds the 3' untranslated region of the mRNA.
AB  - The expression of the nucleus-encoded beta-F1-ATPase gene of oxidative
      phosphorylation is developmentally regulated in the liver at both the
      transcriptional and posttranscriptional levels. In this study we have analyzed
      the potential mechanisms that control the cytoplasmic expression of beta-F1
      ATPase mRNA during liver development. Remarkably, a full-length 3' untranslated
      region (UTR) of the transcript is required for its efficient in vitro
      translation. When the 3' UTR of beta-F1-ATPase mRNA is placed downstream of a
      reporter construct, it functions as a translational enhancer. In vitro
      translation experiments with full-length beta-F1-ATPase mRNA and with a chimeric
      reporter construct containing the 3' UTR of beta-F1-ATPase mRNA suggested the
      existence of an inhibitor of beta-F1-ATPase mRNA translation in the fetal liver.
      Electrophoretic mobility shift assays and UV cross-linking experiments allowed
      the identification of an acutely regulated protein (3'betaFBP) of the liver that
      binds at the 3' UTR of beta-F1-ATPase mRNA. The developmental profile of
      3'betaFBP parallels the reported changes in the translational efficiency of beta
      F1-ATPase mRNA during development. Fractionation of fetal liver extracts revealed
      that the inhibitory activity of beta-F1-ATPase mRNA translation cofractionates
      with 3'-UTR band-shifting activity. Compared to other tissues of the adult rat,
      kidney and spleen extracts showed very high expression levels of 3'betaFBP.
      Translation of beta-F1-ATPase mRNA in the presence of kidney and spleen extracts
      further supported a translational inhibitory role for 3'betaFBP. Mapping
      experiments and a deletion mutant of the 3' UTR revealed that the cis-acting
      element for binding 3'betaFBP is located within a highly conserved region of the
      3' UTR of mammalian beta-F1-ATPase mRNAs. Overall, we have identified a mechanism
      of translational control that regulates the rapid postnatal differentiation of
      liver mitochondria.

PMID- 9271404
TI  - Phenotypic variation in a genetically identical population of mice.
AB  - The parental alleles of an imprinted gene acquire their distinctive methylation
      patterns at different times in development. For the imprinted RSVIgmyc transgene,
      methylation of the maternal allele is established in the oocyte and invariably
      transmitted to the embryo. In contrast, the methylation of the paternal allele
      originates during embryogenesis. Here, we show that the paternal methylation
      pattern among mice with identical genetic backgrounds is subject to extensive
      variation. In addition to this nongenetic variation, the process underlying
      RSVIgmyc methylation in the embryo is also subject to considerable genetic
      regulation. The paternal transgene allele is highly methylated in an inbred
      C57BL/6J strain, whereas it is relatively undermethylated in an inbred FVB/N
      strain. Individual methylation patterns of paternal alleles, and therefore all of
      the variation (nongenetic and genetic) in methylation patterns within an RSVIgmyc
      transgenic line, are established in early embryogenesis. For each mouse, the
      paternal RSVIgmyc allele is unmethylated at the day-3.5 blastocyst stage, and the
      final, adult methylation pattern is found no later than day 8.5 of embryogenesis.
      Because of the strong relationship between RSVIgmyc methylation and expression,
      the variation in methylation is also manifest as variation in transgene
      expression. These results identify embryonic de novo methylation as an important
      source of both genetic and nongenetic contributions to phenotypic variation and,
      as such, further our understanding of the developmental origin of imprinted
      genes.

PMID- 9271405
TI  - The matrix attachment region-binding protein SATB1 participates in negative
      regulation of tissue-specific gene expression.
AB  - The nuclear matrix has been implicated in several cellular processes, including
      DNA replication, transcription, and RNA processing. In particular,
      transcriptional regulation is believed to be accomplished by binding of chromatin
      loops to the nuclear matrix and by the concentration of specific transcription
      factors near these matrix attachment regions (MARs). A number of MAR-binding
      proteins have been identified, but few have been directly linked to tissue
      specific transcription. Recently, we have identified two cellular protein
      complexes (NBP and UBP) that bind to a region of the mouse mammary tumor virus
      (MMTV) long terminal repeat (LTR) previously shown to contain at least two
      negative regulatory elements (NREs) termed the promoter-proximal and promoter
      distal NREs. These NREs are absent from MMTV strains that cause T-cell lymphomas
      instead of mammary carcinomas. We show here that NBP binds to a 22-bp sequence
      containing an imperfect inverted repeat in the promoter-proximal NRE. Previous
      data showed that a mutation (p924) within the inverted repeat elevated basal
      transcription from the MMTV promoter and destabilized the binding of NBP, but not
      UBP, to the proximal NRE. By using conventional and affinity methods to purify
      NBP from rat thymic nuclear extracts, we obtained a single major protein of 115
      kDa that was identified by protease digestion and partial sequencing analysis as
      the nuclear matrix-binding protein special AT-rich sequence-binding protein 1
      (SATB1). Antibody ablation, distamycin inhibition of binding, renaturation and
      competition experiments, and tissue distribution data all confirmed that the NBP
      complex contained SATB1. Similar types of experiments were used to show that the
      UBP complex contained the homeodomain protein Cux/CDP that binds the MAR of the
      intronic heavy-chain immunoglobulin enhancer. By using the p924 mutation within
      the MMTV LTR upstream of the chloramphenicol acetyltransferase gene, we generated
      two strains of transgenic mice that had a dramatic elevation of reporter gene
      expression in lymphoid tissues compared with reporter gene expression in mice
      expressing wild-type LTR constructs. Thus, the 924 mutation in the SATB1-binding
      site dramatically elevated MMTV transcription in lymphoid tissues. These results
      and the ability of the proximal NRE in the MMTV LTR to bind to the nuclear matrix
      clearly demonstrate the role of MAR-binding proteins in tissue-specific gene
      regulation and in MMTV-induced oncogenesis.

PMID- 9271407
TI  - Domains of the Brf component of RNA polymerase III transcription factor IIIB
      (TFIIIB): functions in assembly of TFIIIB-DNA complexes and recruitment of RNA
      polymerase to the promoter.
AB  - Saccharomyces cerevisiae transcription factor IIIB (TFIIIB) is composed of three
      subunits: the TATA-binding protein, the TFIIB-related protein Brf, and B".
      TFIIIB, which is brought to RNA polymerase III-transcribed genes indirectly
      through interaction with DNA-bound TFIIIC or directly through DNA recognition by
      the TATA-binding protein, in turn recruits RNA polymerase III to the promoter. N
      terminally deleted derivatives of Brf have been examined for their ability to
      interact with DNA-bound TFIIIC and with the other components of TFIIIB and for
      participation in transcription. Brf(165-596), lacking 164 N-proximal TFIIB
      homologous amino acids, is competent to participate in the assembly of TFIIIB-DNA
      complexes and in TFIIIC-independent transcription. Even deletion of the entire
      TFIIB-homologous half of the protein, as in Brf(317-596) and Brf(352-596), allows
      some interaction with DNA-bound TBP and with the B" component of TFIIIB to be
      retained. The function of Brf(165-596) in transcription has also been examined in
      the context of B" with small internal deletions. The ability of Brf with this
      sizable N-terminal segment deleted to function in TFIIIC-independent
      transcription requires segments of B" that are individually indispensable
      although required on an either/or basis, in the context of complete Brf. These
      findings suggest a functional complementarity and reciprocity between the Brf and
      B" components of TFIIIB.

PMID- 9271406
TI  - Genetic analysis of the large subunit of yeast transcription factor IIE reveals
      two regions with distinct functions.
AB  - Biochemical analysis of proteins necessary for transcription initiation by
      eukaryotic RNA polymerase II (pol II) has identified transcription factor IIE
      (TFIIE) as an essential component of the reaction. To better understand the role
      of TFIIE in transcription, we isolated conditional alleles of TFA1, the gene
      encoding the large subunit of TFIIE in the yeast Saccharomyces cerevisiae. The
      mutant Tfa1 proteins fall into two classes. The first class causes
      thermosensitive growth due to single amino acid substitutions of the cysteines
      comprising the Zn-binding motif. The second mutant class is made up of proteins
      that are C-terminally truncated and that cause a cold-sensitive growth phenotype.
      The behavior of these mutants suggests that Tfa1p possesses at least two domains
      with genetically distinct functions. The mutations in the Zn-binding motif do not
      affect the mutant protein's stability at the nonpermissive temperature or its
      ability to associate with the small subunit of TFIIE. Our studies further
      determined that wild-type TFIIE can bind to single-stranded DNA in vitro.
      However, this property is unaffected in the mutant TFIIE complexes. Finally, we
      have demonstrated the biological importance of TFIIE in pol II-mediated
      transcription by depleting the Tfa1 protein from the cells and observing a
      concomitant decrease in total poly(A)+ mRNA.

PMID- 9271408
TI  - Functional differences between Stat3alpha and Stat3beta.
AB  - Stat3beta is a short form of Stat3 that differs from the longer form (Stat3alpha)
      by the replacement of the C-terminal 55 amino acid residues of Stat3alpha by 7
      residues specific to Stat3beta. In COS cells transfected with Stat3 expression
      plasmids, both Stat3alpha and Stat3beta were activated for DNA binding and
      transcription by the same set of growth factors and cytokines and both, when
      activated, formed homodimers and heterodimers with Stat1. Only Stat3beta was
      active in the absence of added cytokine or growth factor. Activation of each
      form, including constitutive activation of Stat3beta, was correlated with the
      phosphorylation of tyrosine 705. Activated Stat3beta in transfected COS cells was
      more stable and had greater DNA-binding activity than activated Stat3alpha.
      However, relative to DNA-binding activity, Stat3alpha showed greater
      transcriptional activity than Stat3beta. A mutant of Stat3alpha lacking its
      highly acidic C-terminal 48 amino acids had properties indistinguishable from
      Stat3beta. We conclude that Stat3alpha and Stat3beta have significantly different
      properties due to the presence or absence of the acidic C-terminal tail of
      Stat3alpha rather than the C-terminal sequence peculiar to Stat3beta. In addition
      to its effect on transcription, we speculate that the acidic tail may destabilize
      the active dimeric form of Stat3alpha, resulting in lower DNA-binding activity of
      the Y705-phosphorylated form compared to Stat3beta and in more rapid
      dephosphorylation.

PMID- 9271409
TI  - Role of the human heat shock protein hsp70 in protection against stress-induced
      apoptosis.
AB  - Resistance to stress-induced apoptosis was examined in cells in which the
      expression of hsp70 was either constitutively elevated or inducible by a
      tetracycline-regulated transactivator. Heat-induced apoptosis was blocked in
      hsp70-expressing cells, and this was associated with reduced cleavage of the
      common death substrate protein poly(ADP-ribose) polymerase (PARP). Heat-induced
      cell death was correlated with the activation of the stress-activated protein
      kinase SAPK/JNK (c-Jun N-terminal kinase). Activation of SAPK/JNK was strongly
      inhibited in cells in which hsp70 was induced to a high level, indicating that
      hsp70 is able to block apoptosis by inhibiting signaling events upstream of
      SAPK/JNK activation. In contrast, SAPK/JNK activation was not inhibited by heat
      shock in cells with constitutively elevated levels of hsp70. Cells that
      constitutively overexpress hsp70 resist apoptosis induced by ceramide, a lipid
      signaling molecule that is generated by apoptosis-inducing treatments and is
      linked to SAPK/JNK activation. Similar to heat stress, resistance to ceramide
      induced apoptosis occurs in spite of strong SAPK/JNK activation. Therefore, hsp70
      is also able to inhibit apoptosis at some point downstream of SAPK/JNK
      activation. Since PARP cleavage is prevented in both cell lines, these results
      suggest that hsp70 is able to prevent the effector steps of apoptotic cell death.
      Processing of the CED-3-related protease caspase-3 (CPP32/Yama/apopain) is
      inhibited in hsp70-expressing cells; however, the activity of the mature enzyme
      is not affected by hsp70 in vitro. Caspase processing may represent a critical
      heat-sensitive target leading to cell death that is inhibited by the chaperoning
      function of hsp70. The inhibition of SAPK/JNK signaling and apoptotic protease
      effector steps by hsp70 likely contributes to the resistance to stress-induced
      apoptosis seen in transiently induced thermotolerance.

PMID- 9271410
TI  - Activation of the STAT signaling pathway can cause expression of caspase 1 and
      apoptosis.
AB  - Protein tyrosine kinases activate the STAT (signal transducer and activator of
      transcription) signaling pathway, which can play essential roles in cell
      differentiation, cell cycle control, and development. However, the potential role
      of the STAT signaling pathway in the induction of apoptosis remains unexplored.
      Here we show that gamma interferon (IFN-gamma) activated STAT1 and induced
      apoptosis in both A431 and HeLa cells, whereas epidermal growth factor (EGF)
      activated STAT proteins and induced apoptosis in A431 but not in HeLa cells. EGF
      receptor autophosphorylation and mitogen-activated protein kinase activation in
      response to EGF were similar in both cell lines. The breast cancer cell line MDA
      MB-468 exhibited a similar response to A431 cells, i.e., STAT activation and
      apoptosis correlatively resulted from EGF or IFN-gamma treatment. In addition, in
      a mutant A431 cell line in which STAT activation was abolished, no apoptosis was
      induced by either EGF or IFN-gamma. We further demonstrated that both EGF and IFN
      gamma induced caspase 1 (interleukin-1beta converting enzyme [ICE]) gene
      expression in a STAT-dependent manner. IFN-gamma was unable to induce ICE gene
      expression and apoptosis in either JAK1-deficient HeLa cells (E2A4) or STAT1
      deficient cells (U3A). However, ICE gene expression and apoptosis were induced by
      IFN-gamma in U3A cells into which STAT1 had been reintroduced. Moreover, both EGF
      induced apoptosis and IFN-gamma-induced apoptosis were effectively blocked by Z
      Val-Ala-Asp-fluoromethylketone (ZVAD) in all the cells tested, and studies from
      ICE-deficient cells indicated that ICE gene expression was necessary for IFN
      gamma-induced apoptosis. We conclude that activation of the STAT signaling
      pathway can induce apoptosis through the induction of ICE gene expression.

PMID- 9271411
TI  - Cyclin D1 stimulation of estrogen receptor transcriptional activity independent
      of cdk4.
AB  - Cyclin D1 plays an important role in the development of breast cancer and is
      required for normal breast cell proliferation and differentiation associated with
      pregnancy. We show that ectopic expression of cyclin D1 can stimulate the
      transcriptional activity of the estrogen receptor in the absence of estradiol and
      that this activity can be inhibited by 4-hydroxytamoxifen and ICI 182,780. Cyclin
      D1 can form a specific complex with the estrogen receptor. Stimulation of the
      estrogen receptor by cyclin D1 is independent of cyclin-dependent kinase 4
      activation. Cyclin D1 may manifest its oncogenic potential in breast cancer in
      part through binding to the estrogen receptor and activation of the
      transcriptional activity of the receptor.

PMID- 9271412
TI  - Ras activity late in G1 phase required for p27kip1 downregulation, passage
      through the restriction point, and entry into S phase in growth factor-stimulated
      NIH 3T3 fibroblasts.
AB  - It is well documented that Ras functions as a molecular switch for reentry into
      the cell cycle at the border between G0 and G1 by transducing extracellular
      growth stimuli into early G1 mitogenic signals. In the present study, we
      investigated the role of Ras during the late stage of the G1 phase by using NIH
      3T3 (M17) fibroblasts in which the expression of a dominant negative Ras mutant,
      p21(Ha-Ras[Asn17]), is induced in response to dexamethasone treatment. We found
      that delaying the expression of Ras(Asn17) until late in the G1 phase by
      introducing dexamethasone 3 h after the addition of epidermal growth factor (EGF)
      abolished the downregulation of the p27kip1 cyclin-dependent kinase (CDK)
      inhibitor which normally occurred during this period, with resultant suppression
      of cyclin Ds/CDK4 and cyclin E/CDK2 and G1 arrest. The immunodepletion of p27kip1
      completely eliminated the CDK inhibitor activity from EGF-stimulated,
      dexamethasone-treated cell lysate. The failure of p27kip1 downregulation and G1
      arrest was also observed in cells in which Ras(Asn17) was induced after growth
      stimulation with a phorbol ester or alpha-thrombin and was mimicked by the
      addition late in the G1 phase of inhibitors for phosphatidylinositol-3-kinase.
      Ras-mediated downregulation of p27kip1 involved both the suppression of synthesis
      and the stimulation of the degradation of the protein. Unlike the earlier
      expression of Ras(Asn17) at the border between G0 and G1, its delayed expression
      did not compromise the EGF-stimulated transient activation of extracellular
      signal-regulated kinases or inhibit the stimulated expression of a principal D
      type cyclin, cyclin D1, until close to the border between G1 and S. We conclude
      that Ras plays temporally distinct, phase-specific roles throughout the G1 phase
      and that Ras function late in G1 is required for p27kip1 downregulation and
      passage through the restriction point, a prerequisite for entry into the S phase.

PMID- 9271414
TI  - Conformational changes induced in Hoxb-8/Pbx-1 heterodimers in solution and upon
      interaction with specific DNA.
AB  - Two classes of homeodomain proteins, Hox and Pbx gene products, have the ability
      to bind cooperatively to DNA. In Hox proteins, the homeodomain and a highly
      conserved hexapeptide are required for cooperative DNA binding. In Pbx, the
      homeodomain and a region immediately C terminal of the homeodomain are essential
      for cooperativity. Using fluorescence and circular dichroism spectroscopy, we
      demonstrated that Hox and Pbx proteins interact in the absence of DNA. The
      interaction in solution is accompanied by conformational changes. Furthermore,
      upon interaction with specific DNA, additional conformational changes are induced
      in the Pbx-1/Hoxb-8 heterodimer. These data indicate that prior to DNA binding,
      Hox-Pbx interaction in solution is accompanied by structural alterations. We
      propose that these conformational changes modulate the DNA binding properties of
      these proteins, ultimately resulting in cooperative DNA binding.

PMID- 9271413
TI  - Characterization of strand exchange activity of yeast Rad51 protein.
AB  - The Saccharomyces cerevisiae RAD51 gene product takes part in genetic
      recombination and repair of DNA double strand breaks. Rad51, like Escherichia
      coli RecA, catalyzes strand exchange between homologous circular single-stranded
      DNA (ssDNA) and linear double-stranded DNA (dsDNA) in the presence of ATP and
      ssDNA-binding protein. The formation of joint molecules between circular ssDNA
      and linear dsDNA is initiated at either the 5' or the 3' overhanging end of the
      complementary strand; joint molecules are formed only if the length of the
      overhanging end is more than 1 nucleotide. Linear dsDNAs with recessed
      complementary or blunt ends are not utilized. The polarity of strand exchange
      depends upon which end is used to initiate the formation of joint molecules.
      Joint molecules formed via the 5' end are processed by branch migration in the 3'
      to-5' direction with respect to ssDNA, and joint molecules formed with a 3' end
      are processed in the opposite direction.

PMID- 9271415
TI  - Guide RNA requirement for editing-site-specific endonucleolytic cleavage of
      preedited mRNA by mitochondrial ribonucleoprotein particles in Trypanosoma
      brucei.
AB  - RNA editing in trypanosome mitochondria entails the posttranscriptional internal
      addition and occasional deletion of uridines from precursor mRNAs. Ample evidence
      exists to show that the information specifying the site and number of uridines
      added or deleted comes from small, mitochondrially encoded guide RNAs (gRNAs).
      More recent work indicates that the process involves an enzymatic cascade,
      initiating with an endonucleolytic cleavage of the pre-mRNA at an editing site.
      The cleaved editing site can undergo uridine (U) addition to or deletion from the
      3' end of the 5' fragment via a mitochondrial terminal uridylyl transferase
      (TUTase) or terminal uridylyl exonuclease, respectively. Mitochondrial RNA ligase
      subsequently rejoins the mRNA. Activities to carry out these processes have been
      found in trypanosome mitochondria, including an editing-site-specific
      endonuclease activity which cleaves preedited but not edited mRNAs. We have found
      that this enzymatic activity cosediments with the same 19S ribonucleoprotein
      particle previously shown to contain TUTase, RNA ligase, and gRNAs and remains
      stable after salt treatment. Depletion of endogenous cytochrome b gRNAs by the
      addition of complementary oligonucleotides in vitro completely inhibits editing
      site cleavage of synthetic preedited cytochrome b mRNA. The addition of synthetic
      cognate gRNA for cytochrome b but not unrelated small RNA restores editing-site
      cleavage. These studies show that in addition to specifying the site and number
      of uridines added or deleted, gRNAs provide the necessary information for
      cleavage by the editing-site-specific endonuclease.

PMID- 9271417
TI  - The orphan nuclear receptor estrogen-related receptor alpha is a transcriptional
      regulator of the human medium-chain acyl coenzyme A dehydrogenase gene.
AB  - Estrogen-related receptor alpha (ERR alpha) is an orphan member of the
      superfamily of nuclear hormone receptors. ERR alpha was initially isolated based
      on its sequence homology to the estrogen receptor but is not activated by classic
      estrogens. To identify possible physiologic functions for this orphan receptor,
      we cloned the mouse ERR alpha cDNA and used it to characterize the expression of
      ERR alpha transcripts and to identify potential ERR alpha target genes. RNA in
      situ hybridization studies detect ERR alpha transcripts in an organ-specific
      manner through mid- to late embryonic development, with persistent high-level
      expression in brown adipose tissue and intestinal mucosa. In the adult mouse, ERR
      alpha is most highly expressed in kidney, heart, and brown adipocytes, tissues
      which preferentially metabolize fatty acids. Binding site selection experiments
      show that ERR alpha preferentially binds to an ERR alpha response element (ERRE)
      containing a single consensus half-site, TNAAGGTCA. An ERRE is present in the 5'
      flanking region of the gene encoding medium-chain acyl coenzyme A dehydrogenase
      (MCAD), a key enzyme involved in the mitochondrial beta-oxidation of fat. The
      MCAD nuclear receptor response element 1 (NRRE-1) interacts in vitro with ERR
      alpha expressed in COS-7 cells. Supershift experiments show that endogenous ERR
      alpha present in nuclear extracts obtained from a brown fat tumor cell line (HIB)
      interacts with NRRE-1. In the absence of its putative ligand, ERR alpha does not
      activate the MCAD promoter in transient transfection studies; however, a VP16-ERR
      alpha chimera activates natural and synthetic promoters containing NRRE-1. In
      addition, ERR alpha efficiently represses retinoic acid induction mediated by
      NRRE-1. These results demonstrate that ERR alpha can control the expression of
      MCAD through the NRRE-1 and thus may play an important role in regulating
      cellular energy balance in vivo.

PMID- 9271416
TI  - Distinct functional properties of IkappaB alpha and IkappaB beta.
AB  - The biological activity of the transcription factor NF-kappaB is controlled
      mainly by the IkappaB alpha and IkappaB beta proteins, which restrict NF-kappaB
      to the cytoplasm and inhibit its DNA binding activity. Here, we carried out
      experiments to determine and compare the mechanisms by which IkappaB alpha and
      IkappaB beta inhibit NF-kappaB-dependent transcriptional activation. First, we
      found that in vivo IkappaB alpha is a stronger inhibitor of NF-kappaB than is
      IkappaB beta. This difference is directly correlated with their abilities to
      inhibit NF-kappaB binding to DNA in vitro and in vivo. Moreover, IkappaB alpha,
      but not IkappaB beta, can remove NF-kappaB from functional preinitiation
      complexes in in vitro transcription experiments. Second, we showed that both
      IkappaBs function in vivo not only in the cytoplasm but also in the nucleus,
      where they inhibit NF-kappaB binding to DNA. Third, the inhibitory activity of
      IkappaB beta, but not that of IkappaB alpha, is facilitated by phosphorylation of
      the C-terminal PEST sequence by casein kinase II and/or by the interaction of NF
      kappaB with high-mobility group protein I (HMG I) on selected promoters. The
      unphosphorylated form of IkappaB beta forms stable ternary complexes with NF
      kappaB on the DNA either in vitro or in vivo. These experiments suggest that
      IkappaB alpha works as a postinduction repressor of NF-kappaB independently of
      HMG I, whereas IkappaB beta functions preferentially in promoters regulated by
      the NF-kappaB/HMG I complexes.

PMID- 9271418
TI  - Distinct tyrosine autophosphorylation sites negatively and positively modulate
      neu-mediated transformation.
AB  - A number of cytoplasmic signaling molecules are thought to mediate mitogenic
      signaling from the activated Neu receptor tyrosine kinase through binding
      specific phosphotyrosine residues located within the intracellular portion of
      Neu/c-ErbB-2. An activated neu oncogene containing tyrosine-to-phenylalanine
      substitutions at each of the known autophosphorylation sites was generated and
      assessed for its specific transforming potential in Rat1 and NIH 3T3 fibroblasts.
      Mutation of these sites resulted in a dramatic impairment of the transforming
      potential of neu. To assess the role of these tyrosine phosphorylation sites in
      cellular transformation, the transforming potential of a series of mutants in
      which individual tyrosine residues were restored to this transformation
      debilitated neu mutant was evaluated. Reversion of any one of four mutated sites
      to tyrosine residues restored wild-type transforming activity. While each of
      these transforming mutants displayed Ras-dependent signaling, the transforming
      activity of two of these mutants was correlated with their ability to bind either
      the GRB2 or SHC adapter molecules that couple receptor tyrosine kinases to the
      Ras signaling pathway. By contrast, restoration of a tyrosine residue located at
      position 1028 completely suppressed the basal transforming activity of this
      mutated neu molecule or other transforming neu molecules which possessed single
      tyrosine residues. These data argue that the transforming potential of activated
      neu is mediated both by positive and negative regulatory tyrosine phosphorylation
      sites.

PMID- 9271419
TI  - The insulin-induced signalling pathway leading to S6 and initiation factor 4E
      binding protein 1 phosphorylation bifurcates at a rapamycin-sensitive point
      immediately upstream of p70s6k.
AB  - Employing specific inhibitors and docking-site mutants of growth factor
      receptors, recent studies have indicated that the insulin-induced increase in 40S
      ribosomal protein S6 and initiation factor 4E binding protein 1 (4E-BP1)
      phosphorylation is mediated by the mTOR/FRAP-p70s6k signal transduction pathway.
      However, it has not been resolved whether the phosphorylation of both proteins is
      mediated by p70s6k or whether they reside on parallel pathways which bifurcate
      upstream of p70s6k. Here we have used either rapamycin-resistant, kinase-dead, or
      wild-type p70s6k variants to distinguish between these possibilities. The
      rapamycin-resistant p70s6k, which has high constitutive activity, was able to
      signal to S6 in the absence of insulin and to prevent the rapamycin-induced block
      of S6 phosphorylation. This same construct did not increase the basal state of 4E
      BP1 phosphorylation or protect it from the rapamycin-induced block in
      phosphorylation. Unexpectedly, the rapamycin-resistant p70s6k inhibited insulin
      induced 4E-BP1 phosphorylation in a dose-dependent manner. This effect was
      mimicked by the kinase-dead and wild-type p70s6k constructs, which also blocked
      insulin-induced dissociation of 4E-BP1 from initiation factor 4E. Both the kinase
      dead and wild-type constructs also blocked reporter p70s6k activation, although
      only the kinase-dead p70s6k had a dominant-interfering effect on S6
      phosphorylation. Analysis of phosphopeptides from reporter 4E-BP1 and p70s6k
      revealed that the kinase-dead p70s6k affected the same subset of sites as
      rapamycin in both proteins. The results demonstrate, for the first time, that
      activated p70s6k mediates increased S6 phosphorylation in vivo. Furthermore, they
      show that increased 4E-BP1 phosphorylation is controlled by a parallel signalling
      pathway that bifurcates immediately upstream of p70s6k, with the two pathways
      sharing a common rapamycin-sensitive activator.

PMID- 9271420
TI  - Clusters of S1 nuclease-hypersensitive sites induced in vivo by DNA damage.
AB  - DNA end-labeling procedures were used to analyze both the frequency and
      distribution of DNA strand breaks in mammalian cells exposed or not to different
      types of DNA-damaging agents. The 3' ends were labeled by T4 DNA polymerase
      catalyzed nucleotide exchange carried out in the absence or presence of
      Escherichia coli endonuclease IV to cleave abasic sites and remove 3' blocking
      groups. Using this sensitive assay, we show that DNA isolated from human cells or
      mouse tissues contains variable basal levels of DNA strand interruptions which
      are associated with normal bioprocesses, including DNA replication and repair. On
      the other hand, distinct dose-dependent patterns of DNA damage were assessed
      quantitatively in cultured human cells exposed briefly to menadione,
      methylmethane sulfonate, topoisomerase II inhibitors, or gamma rays. In vivo
      induction of single-strand breaks and abasic sites by methylmethane sulfonate was
      also measured in several mouse tissues. The genomic distribution of these lesions
      was investigated by DNA cleavage with the single-strand-specific S1 nuclease.
      Strikingly similar cleavage patterns were obtained with all DNA-damaging agents
      tested, indicating that the majority of S1-hypersensitive sites detected were not
      randomly distributed over the genome but apparently were clustered in damage
      sensitive regions. The parallel disappearance of 3' ends and loss of S1
      hypersensitive sites during post-gamma-irradiation repair periods indicates that
      these sites were rapidly repaired single-strand breaks or gaps (2- to 3-min half
      life). Comparison of S1 cleavage patterns obtained with gamma-irradiated DNA and
      gamma-irradiated cells shows that chromatin structure was the primary determinant
      of the distribution of the DNA damage detected.

PMID- 9271421
TI  - Multiple-drug-resistance phenomenon in the yeast Saccharomyces cerevisiae:
      involvement of two hexose transporters.
AB  - In the yeast Saccharomyces cerevisiae, multidrug resistance to unrelated
      chemicals can result from overexpression of ATP-binding cassette (ABC)
      transporters such as Pdr5p, Snq2p, and Yor1p. Expression of these genes is under
      the control of two homologous zinc finger-containing transcription regulators,
      Pdr1p and Pdr3p. Here, we describe the isolation, by an in vivo screen, of two
      new Pdr1p-Pdr3p target genes: HXT11 and HXT9. HXT11 and HXT9, encoding nearly
      identical proteins, have a high degree of identity to monosaccharide transporters
      of the major facilitator superfamily (MFS). In this study, we show that the HXT11
      product, which allows glucose uptake in a glucose permease mutant (rag1) strain
      of Kluyveromyces lactis, is also involved in the pleiotropic drug resistance
      process. Loss of HXT11 and/or HXT9 confers cycloheximide, sulfomethuron methyl,
      and 4-NQO (4-nitroquinoline-N-oxide) resistance. Conversely, HXT11 overexpression
      increases sensitivity to these drugs in the wild-type strain, an effect which is
      more pronounced in a strain having both PDR1 and PDR3 deleted. These data show
      that the two putative hexose transporters Hxt11p and Hxt9p are transcriptionally
      regulated by the transcription factors Pdr1p and Pdr3p, which are known to
      regulate the production of ABC transporters required for drug resistance in
      yeast. We thus demonstrate the existence of genetic interactions between genes
      coding for two classes of transporters (ABC and MFS) to control the multidrug
      resistance process.

PMID- 9271422
TI  - Identification of a member of a DNA-dependent ATPase family that causes
      interference with silencing.
AB  - DNA in eukaryotic cells is packed in tandem repeats of nucleosomes or higher
      order chromatin structures, which present obstacles to many cellular processes
      that require protein-DNA interactions, such as transcription, DNA repair, and
      recombination. To find proteins that are involved in increasing the accessibility
      of specific DNA regions in yeast, we used a genetic approach that exploited
      transcriptional silencing normally occurring at HML and HMR loci. The silencing
      is mediated by cis-acting silencer elements and is thought to require the
      formation of a special chromatin structure that prevents accessibility to the
      silenced DNA. A previously uncharacterized gene, termed DIS1, was isolated from a
      screen for genes that interfere with silencing when overexpressed. DIS1 encodes a
      protein with conserved motifs that are present in a family of DNA-dependent
      ATPases, the SWI2/SNF2-like proteins. Overproduction of N-terminal half of DIS1
      protein interfered specifically with ectopic silencing used in the screen as well
      as HMR E silencing. Two-hybrid studies revealed a specific interaction between
      the N terminus of DIS1 and the C-terminal half of SIR4, a protein essential for
      silencing. Cells with a dis1 knockout mutation had significantly lower mating
      type switching rate. These results suggest that DIS1 may contribute to making the
      silenced DNA template at HM loci more accessible during the mating-type switching
      process.

PMID- 9271423
TI  - Functional equivalency and diversity of cis-acting elements among yeast
      replication origins.
AB  - The DNA replication origins of the yeast Saccharomyces cerevisiae require several
      short functional elements, most of which are not conserved in sequence. To better
      characterize ARS305, a replicator from a chromosomal origin, we swapped
      functional DNA elements of ARS305 with defined elements of ARS1. ARS305 contains
      elements that are functionally exchangeable with ARS1 A and B1 elements, which
      are known to bind the origin recognition complex; however, the ARS1 A element
      differs in that it does not require a 3' box adjacent to the essential
      autonomously replicating sequence consensus. At the position corresponding to
      ARS1 B3, ARS305 has a novel element, B4, that can functionally substitute for
      every type of short element (B1, B2, and B3) in the B domain. Unexpectedly, the
      replacement of element B4 by ARS1 B3, which binds ABF1p and is known as a
      replication enhancer, inhibited ARS305 function. ARS305 has no short functional
      element at or near positions corresponding to the B2 elements in ARS1 and ARS307
      but contains an easily unwound region whose functional importance was supported
      by a broad G+C-rich substitution mutation. Surprisingly, the easily unwound
      region can functionally substitute for the ARS1 B2 element, even though ARS1 B2
      was found to possess a distinct DNA sequence requirement. The functionally
      conserved B2 element in ARS307 contains a known sequence requirement, and helical
      stability analysis of linker and minilinker mutations suggested that B2 also
      contains a DNA unwinding element (DUE). Our findings suggest that yeast
      replication origins employ a B2 element or a DUE to mediate a common function,
      DNA unwinding during initiation, although not necessarily through a common
      mechanism.

PMID- 9271424
TI  - FIN13, a novel growth factor-inducible serine-threonine phosphatase which can
      inhibit cell cycle progression.
AB  - We have identified a novel type 2C serine-threonine phosphatase, FIN13, whose
      expression is induced by fibroblast growth factor 4 and serum in late G1 phase.
      The protein encoded by FIN13 cDNA includes N- and C-terminal domains with
      significant homologies to type 2C phosphatases, a domain homologous to collagen,
      and an acidic domain. FIN13 expression predominates in proliferating tissues.
      Bacterially expressed FIN13 and FIN13 expressed in mammalian cells exhibit serine
      threonine phosphatase activity, which requires Mn2+ and is insensitive to
      inhibition by okadaic acid. FIN13 is localized in the nuclei of transiently
      transfected cells. Cotransfection of FIN13-expressing plasmids with a plasmid
      that expresses the neomycin resistance gene inhibits the growth of drug-resistant
      colonies in NIH 3T3, HeLa and Rat-1 cells. In transiently transfected cells,
      FIN13 inhibits DNA synthesis and results in the accumulation of cells in G1 and
      early S phases. Similarly, the induction of expression of FIN13 under the control
      of a tetracycline-regulated promoter in NIH 3T3 cells leads to growth inhibition,
      with accumulation of cells in G1 and early S phases. Thus, overexpression and/or
      unregulated expression of FIN13 inhibits cell cycle progression, indicating that
      the physiological role of this phosphatase may be that of regulating the orderly
      progression of cells through the mitotic cycle by dephosphorylating specific
      substrates which are important for cell proliferation.

PMID- 9271425
TI  - A deletion mutation in the SH2-N domain of Shp-2 severely suppresses
      hematopoietic cell development.
AB  - Shp-1 and Shp-2 are cytoplasmic protein tyrosine phosphatases that contain two
      Src homology 2 (SH2) domains. A negative regulatory role of Shp-1 in
      hematopoiesis has been strongly implicated by the phenotype of motheaten mice
      with a mutation in the Shp-1 locus, which is characterized by leukocyte
      hypersensitivity, deregulated mast cell function, and excessive erythropoiesis. A
      targeted deletion of 65 amino acids in the N-terminal SH2 (SH2-N) domain of Shp-2
      leads to an embryonic lethality at midgestation in homozygous mutant mice. To
      further dissect the Shp-2 function in hematopoietic development, we have isolated
      homozygous Shp-2 mutant embryonic stem (ES) cells. Significantly reduced
      hematopoietic activity was observed when the mutant ES cells were allowed to
      differentiate into embryoid bodies (EBs), compared to the wild-type and
      heterozygous ES cells. Further analysis of ES cell differentiation in vitro
      showed that mutation in the Shp-2 locus severely suppressed the development of
      primitive and definitive erythroid progenitors and completely blocked the
      production of progenitor cells for granulocytes-macrophages and mast cells.
      Reverse transcriptase PCR analysis of the mutant EBs revealed reduced expression
      of several specific marker genes that are induced during blood cell
      differentiation. Stem cell factor induction of mitogen-activated protein kinase
      activity was also blocked in Shp-2 mutant cells. Taken together, these results
      indicate that Shp-2 is an essential component and primarily plays a positive role
      in signaling pathways that mediate hematopoiesis in mammals. Furthermore,
      stimulation of its catalytic activity is not sufficient, while interaction via
      the SH2 domains with the targets or regulators is necessary for its biological
      functions in cells. The in vitro ES cell differentiation assay can be used as a
      biological tool in dissecting cytoplasmic signaling pathways.

PMID- 9271426
TI  - Induction of S-phase entry by E2F transcription factors depends on their nuclear
      localization.
AB  - The E2F transcription factors are essential for regulating the correct timing of
      activation of several genes whose products are implicated in cell proliferation
      and DNA replication. The E2Fs are targets for negative regulation by the
      retinoblastoma protein family, which includes pRB, p107, and p130, and they are
      in a pathway that is frequently found altered in human cancers. There are five
      members of the E2F family, and they can be divided into two functional subgroups.
      Whereas, upon overexpression, E2F-1, -2, and -3 induce S phase in quiescent
      fibroblasts and override G1 arrests mediated by the p16INK4A tumor suppressor
      protein or neutralizing antibodies to cyclin D1, E2F-4 and -5 do not. Using E2F-1
      and E2F-4 as representatives of the two subgroups, we showed here, by
      constructing a set of chimeric proteins, that the amino terminus of E2F-1 is
      sufficient to confer S-phase-inducing potential as well as the ability to
      efficiently transactivate an E2F-responsive promoter to E2F-4. We found that the
      E2F-1 amino terminus directs chimeric proteins to the nucleus. Surprisingly, a
      short nuclear localization signal derived from simian virus 40 large T antigen
      could perfectly substitute for the presence of the E2F-1 amino terminus in these
      assays. Thus, nuclearly localized E2F-4, when overexpressed, displayed biological
      activities similar to those of E2F-1. Furthermore, we showed that nuclear
      localization of endogenous E2F-4 is cell cycle regulated, with E2F-4 being
      nuclear in the G0 and early G1 phases and mainly cytoplasmic after the pRB family
      members have become phosphorylated. We propose a novel mechanism for the
      regulation of E2F-dependent transcription in which E2F-4 regulates transcription
      only from G0 until mid- to late G1 phase whereas E2F-1 is active in late G1 and S
      phases, until it is inactivated by cyclin A-dependent kinase in late S phase.

PMID- 9271427
TI  - The Drosophila bifocal gene encodes a novel protein which colocalizes with actin
      and is necessary for photoreceptor morphogenesis.
AB  - Photoreceptor cells of the Drosophila compound eye begin to develop specialized
      membrane foldings at the apical surface in midpupation. The microvillar structure
      ultimately forms the rhabdomere, an actin-rich light-gathering organelle with a
      characteristic shape and morphology. In a P-element transposition screen, we
      isolated mutations in a gene, bifocal (bif), which is required for the
      development of normal rhabdomeres. The morphological defects seen in bif mutant
      animals, in which the distinct contact domains established by the newly formed
      rhabdomeres are abnormal, first become apparent during midpupal development. The
      later defects seen in the mutant adult R cells are more dramatic, with the
      rhabdomeres enlarged, elongated, and frequently split. bif encodes a novel
      putative protein of 1063 amino acids which is expressed in the embryo and the
      larval eye imaginal disc in a pattern identical to that of F actin. During pupal
      development, Bif localizes to the base of the filamentous actin associated with
      the forming rhabdomeres along one side of the differentiating R cells. On the
      basis of its subcellular localization and loss-of-function phenotype, we discuss
      possible roles of Bif in photoreceptor morphogenesis.

PMID- 9271428
TI  - Control of microtubule dynamics by oncoprotein 18: dissection of the regulatory
      role of multisite phosphorylation during mitosis.
AB  - Oncoprotein 18 (Op18; also termed p19, 19K, metablastin, stathmin, and prosolin)
      is a conserved protein that regulates microtubule (MT) dynamics. Op18 is
      multisite phosphorylated on four Ser residues during mitosis; two of these Ser
      residues, Ser-25 and Ser-38, are targets for cyclin-dependent protein kinases
      (CDKs), and the other two Ser residues, Ser-16 and Ser-63, are targets for an
      unidentified protein kinase. Mutations of the two CDK sites have recently been
      shown to result in a mitotic block caused by destabilization of MTs. To
      understand the role of Op18 in regulation of MT dynamics during mitosis, in this
      study we dissected the functions of all four phosphorylation sites of Op18 by
      combining genetic, morphological, and biochemical analyses. The data show that
      all four phosphorylation sites are involved in switching off Op18 activity during
      mitosis, an event that appears to be essential for formation of the spindle
      during metaphase. However, the mechanisms by which specific sites down-regulate
      Op18 activity differ. Hence, dual phosphorylation on the CDK sites Ser-25 and Ser
      38 appears to be required for phosphorylation of Ser-16 and Ser-63; however, by
      themselves, the CDK sites are of only minor importance in direct regulation of
      Op18 activity. Subsequent phosphorylation of either Ser-16, Ser-63, or both
      efficiently switches off Op18 activity.

PMID- 9271429
TI  - Evidence for a requirement for both phospholipid and phosphotyrosine binding via
      the Shc phosphotyrosine-binding domain in vivo.
AB  - The adapter protein Shc is a critical component of mitogenic signaling pathways
      initiated by a number of receptors. Shc can directly bind to several tyrosine
      phosphorylated receptors through its phosphotyrosine-binding (PTB) domain, and a
      role for the PTB domain in phosphotyrosine-mediated signaling has been well
      documented. The structure of the Shc PTB domain demonstrated a striking homology
      to the structures of pleckstrin homology domains, which suggested acidic
      phospholipids as a second ligand for the Shc PTB domain. Here we demonstrate that
      Shc binding via its PTB domain to acidic phospholipids is as critical as binding
      to phosphotyrosine for leading to Shc phosphorylation. Through structure-based,
      targeted mutagenesis of the Shc PTB domain, we first identified the residues
      within the PTB domain critical for phospholipid binding in vitro. In vivo, the
      PTB domain was essential for localization of Shc to the membrane, as mutant Shc
      proteins that failed to interact with phospholipids in vitro also failed to
      localize to the membrane. We also observed that PTB domain-dependent targeting to
      the membrane preceded the PTB domain's interaction with the tyrosine
      phosphorylated receptor and that both events were essential for tyrosine
      phosphorylation of Shc following receptor activation. Thus, Shc, through its
      interaction with two different ligands, is able to accomplish both membrane
      localization and binding to the activated receptor via a single PTB domain.

PMID- 9271430
TI  - A role for the ETS domain transcription factor PEA3 in myogenic differentiation.
AB  - Activation of adult myoblasts called satellite cells during muscle degeneration
      is an important aspect of muscle regeneration. Satellite cells are believed to be
      the only myogenic stem cells in adult skeletal muscle and the source of
      regenerating muscle fibers. Upon activation, satellite cells proliferate, migrate
      to the site of degeneration, and become competent to fuse and differentiate. We
      show here that the transcription factor polyomavirus enhancer activator 3 (PEA3)
      is expressed in adult myoblasts in vitro when they are proliferative and during
      the early stages of differentiation. Overexpression of PEA3 accelerates
      differentiation, whereas blocking of PEA3 function delays myoblast fusion. PEA3
      activates gene expression following binding to the ets motif most efficiently in
      conjunction with the transcription factor myocyte enhancer factor 2 (MEF2). In
      vivo, PEA3 is expressed in satellite cells only after muscle degeneration. Taken
      together, these results suggest that PEA3 is an important regulator of activated
      satellite cell function.

PMID- 9271431
TI  - Palindrome resolution and recombination in the mammalian germ line.
AB  - Genetic instability is promoted by unusual sequence arrangements and DNA
      structures. Hairpin DNA structures can form from palindromes and from triplet
      repeats, and they are also intermediates in V(D)J recombination. We have measured
      the genetic stability of a large palindrome which has the potential to form a one
      stranded hairpin or a two-stranded cruciform structure and have analyzed
      recombinants at the molecular level. A palindrome of 15.3 kb introduced as a
      transgene was found to be transmitted at a normal Mendelian ratio in mice, in
      striking contrast to the profound instability of large palindromes in prokaryotic
      systems. In a significant number of progeny mice, however, the palindromic
      transgene is rearranged; between 15 and 56% of progeny contain rearrangements.
      Rearrangements within the palindromic repeat occur both by illegitimate and
      homologous, reciprocal recombination. Gene conversion within the transgene locus,
      as quantitated by a novel sperm fluorescence assay, is also elevated.
      Illegitimate events often take the form of an asymmetric deletion that eliminates
      the central symmetry of the palindrome. Such asymmetric transgene deletions,
      including those that maintain one complete half of the palindromic repeat, are
      stabilized so that they cannot undergo further illegitimate rearrangements, and
      they also exhibit reduced levels of gene conversion. By contrast, transgene
      rearrangements that maintain the central symmetry continue to be unstable. Based
      on the observed events, we propose that one mechanism promoting the instability
      of the palindrome may involve breaks generated at the hairpin structure by a
      hairpin-nicking activity, as previously detected in somatic cells. Because
      mammalian cells are capable of efficiently repairing chromosome breaks through
      nonhomologous processes, the resealing of such breaks introduces a stabilizing
      asymmetry at the center of the palindrome. We propose that the ability of
      mammalian cells to eliminate the perfect symmetry in a palindromic sequence may
      be an important DNA repair pathway, with implications regarding the metabolism of
      palindromic repeats, the mutability of quasipalindromic triplet repeats, and the
      early steps in gene amplification events.

PMID- 9271432
TI  - Ectopic gene targeting exhibits a bimodal distribution of integration in murine
      cells, indicating that both intra- and interchromosomal sites are accessible to
      the targeting vector.
AB  - Ectopic gene targeting is an alternative outcome of the gene targeting process in
      which the targeting vector acquires sequences from the genomic target but
      proceeds to integrate elsewhere in the genome. Using two-color fluorescent in
      situ hybridization analysis, we have determined the integration sites of the gene
      targeting vector with respect to the target locus in a murine fibroblast line
      (LTA). We found that for ectopic gene targeting the distribution of integration
      sites was bimodal, being either within 3 Mb of the target or on chromosomes
      distinct from the chromosome carrying the target locus. Inter- and
      intrachromosomal sites appeared to be equally accessible to the targeting vector,
      with site-specific variations. Interestingly, interphase analysis indicated that
      vector sequences which had integrated ectopically in chromosomes other than the
      target colocalized with the target locus at a significant frequency compared to
      that of colocalization to random unlinked loci. We propose that ectopic gene
      targeting could be used to determine which chromosomal domains within the genome
      are accessible to a given genetic locus. Thus, recombination access mapping may
      present a new paradigm for the analysis of DNA accessibility and interaction
      within the genome.

PMID- 9271433
TI  - Groucho-dependent and -independent repression activities of Runt domain proteins.
AB  - Runt domain proteins are transcriptional regulators that specify cell fates for
      processes extending from pattern formation in insects to leukemogenesis in
      humans. Runt domain family members are defined based on the presence of the 128
      amino-acid Runt domain, which is necessary and sufficient for sequence-specific
      DNA binding. We demonstrate an evolutionarily conserved protein-protein
      interaction between Runt domain proteins and the corepressor Groucho. The
      interaction, however, is independent of the Runt domain and can be mapped to a 5
      amino-acid sequence, VWRPY, present at the C terminus of all Runt domain
      proteins. Drosophila melanogaster Runt and Groucho interact genetically; the in
      vivo repression of a subset of Runt-regulated genes is dependent on the
      interaction with Groucho and is sensitive to Groucho dosage. Runt's repression of
      one gene, engrailed, is independent of VWRPY and Groucho, thus demonstrating
      alternative mechanisms for repression by Runt domain proteins. Unlike other
      transcriptional regulatory proteins that interact with Groucho, Runt domain
      proteins are known to activate transcription. This suggests that the Runt domain
      protein-Groucho interaction may be regulated.

PMID- 9271436
TI  - Methylation of discrete regions of the O6-methylguanine DNA methyltransferase
      (MGMT) CpG island is associated with heterochromatinization of the MGMT
      transcription start site and silencing of the gene.
AB  - O6-Methylguanine DNA methyltransferase (MGMT) repairs the mutagenic and cytotoxic
      O6-alkylguanine lesions produced by environmental carcinogens and the
      chemotherapeutic nitrosoureas. As such, MGMT-mediated repair of O6-alkylguanine
      lesions constitutes a major form of resistance to nitrosourea chemotherapy and
      makes control of MGMT expression of clinical interest. The variability of
      expression in cell lines and tissues, along with the ease with which the MGMT
      phenotype reverts under various conditions, suggests that MGMT is under
      epigenetic control. One such epigenetic mechanism, 5-methylation of cytosines,
      has been linked to MGMT expression. We have used an isogenic human multiple
      myeloma tumor cell line model composed of an MGMT-positive parent cell line, RPMI
      8226/S, and its MGMT-negative variant, termed 8226/V, to study the control of
      MGMT expression. The loss of MGMT activity in 8226/V was found to be due to the
      loss of detectable MGMT gene expression. Bisulfite sequencing of the MGMT CpG
      island promoter revealed large increases in the levels of CpG methylation within
      discrete regions of the 8226/V MGMT CpG island compared to those in 8226/S. These
      changes in CpG methylation are associated with local heterochromatinization of
      the 8226/V MGMT transcription start site and provide a likely mechanism for the
      loss of MGMT transcription in 8226/V.

PMID- 9271434
TI  - High-intensity Raf signal causes cell cycle arrest mediated by p21Cip1.
AB  - Activated Raf has been linked to such opposing cellular responses as the
      induction of DNA synthesis and the inhibition of proliferation. However, it
      remains unclear how such a switch in signal specificity is regulated. We have
      addressed this question with a regulatable Raf-androgen receptor fusion protein
      in murine fibroblasts. We show that Raf can cause a G1-specific cell cycle arrest
      through induction of p21Cip1. This in turn leads to inhibition of cyclin D- and
      cyclin E-dependent kinases and an accumulation of hypophosphorylated Rb.
      Importantly, this behavior can be observed only in response to a strong Raf
      signal. In contrast, moderate Raf activity induces DNA synthesis and is
      sufficient to induce cyclin D expression. Therefore, Raf signal specificity can
      be determined by modulation of signal strength presumably through the induction
      of distinct protein expression patterns. Similar to induction of Raf, a strong
      induction of activated Ras via a tetracycline-dependent promoter also causes
      inhibition of proliferation and p21Cip1 induction at high expression levels.
      Thus, p21Cip1 plays a key role in determining cellular responses to Ras and Raf
      signalling. As predicted by this finding we show that Ras and loss of p21
      cooperate to confer a proliferative advantage to mouse embryo fibroblasts.

PMID- 9271435
TI  - Raf-induced proliferation or cell cycle arrest is determined by the level of Raf
      activity with arrest mediated by p21Cip1.
AB  - The Raf family of protein kinases display differences in their abilities to
      promote the entry of quiescent NIH 3T3 cells into the S phase of the cell cycle.
      Although conditional activation of deltaA-Raf:ER promoted cell cycle progression,
      activation of deltaRaf-1:ER and deltaB-Raf:ER elicited a G1 arrest that was not
      overcome by exogenously added growth factors. Activation of all three deltaRaf:ER
      kinases led to elevated expression of cyclin D1 and cyclin E and reduced
      expression of p27Kip1. However, activation of deltaB-Raf:ER and deltaRaf-1:ER
      induced the expression of p21Cip1, whereas activation of deltaA-Raf:ER did not. A
      catalytically potentiated form of deltaA-Raf:ER, generated by point mutation,
      strongly induced p21Cip1 expression and elicited cell cycle arrest similarly to
      deltaB-Raf:ER and deltaRaf-1:ER. These data suggested that the strength and
      duration of signaling by Raf kinases might influence the biological outcome of
      activation of this pathway. By titration of deltaB-Raf:ER activity we
      demonstrated that low levels of Raf activity led to activation of cyclin D1-cdk4
      and cyclin E-cdk2 complexes and to cell cycle progression whereas higher Raf
      activity elicited cell cycle arrest correlating with p21Cip1 induction and
      inhibition of cyclin-cdk activity. Using green fluorescent protein-tagged forms
      of deltaRaf-1:ER in primary mouse embryo fibroblasts (MEFs) we demonstrated that
      p21Cip1 was induced by Raf in a p53-independent manner, leading to cell cycle
      arrest. By contrast, activation of Raf in p21Cip1(-/-) MEFs led to a robust
      mitogenic response that was similar to that observed in response to platelet
      derived growth factor. These data indicate that, depending on the level of kinase
      activity, Raf can elicit either cell cycle progression or cell cycle arrest in
      mouse fibroblasts. The ability of Raf to elicit cell cycle arrest is strongly
      associated with its ability to induce the expression of the cyclin-dependent
      kinase inhibitor p21Cip1 in a manner that bears analogy to alpha-factor arrest in
      Saccharomyces cerevisiae. These data are consistent with a role for Raf kinases
      in both proliferation and differentiation of mammalian cells.

PMID- 9271437
TI  - Synergy between suppressor of Hairless and Notch in regulation of Enhancer of
      split m gamma and m delta expression.
AB  - The Notch signaling pathway is known to regulate cell fate decisions in a variety
      of organisms from worms to humans. Although several components of the pathway
      have been characterized, the actual mechanism and molecular results of signaling
      remain elusive. We have examined the role of the Notch signaling pathway in the
      transcriptional regulation of two Drosophila Enhancer of split [E(spl)] genes,
      whose gene products have been shown to be downstream players in the pathway.
      Using a reporter assay system in Drosophila tissue culture cells, we have
      observed a significant induction of E(spl) m gamma and m delta expression after
      cotransfection with activated Notch. Characterization of the 5' regulatory
      regions of these two genes led to the identification of a number of target sites
      for the Suppressor of Hairless [Su(H)] protein, a transcription factor activated
      by Notch signaling. We show that Notch-inducible expression of E(spl) m gamma and
      m delta both in cultured cells and in vivo is dependent on functional Su(H).
      Although overexpression of Su(H) augments the level of induction of the reporter
      genes by activated Notch, Su(H) alone is insufficient to produce high levels of
      transcriptional activation. Despite the synergy observed between activated Notch
      and Su(H), the former affects neither the nuclear localization nor the DNA
      binding activity of the latter.

PMID- 9271439
TI  - Ectopic expression of cyclin D1 but not cyclin E induces anchorage-independent
      cell cycle progression.
AB  - Normal fibroblasts are dependent on adhesion to a substrate for cell cycle
      progression. Adhesion-deprived Rat1 cells arrest in the G1 phase of the cell
      cycle, with low cyclin E-dependent kinase activity, low levels of cyclin D1
      protein, and high levels of the cyclin-dependent kinase inhibitor p27kip1. To
      understand the signal transduction pathway underlying adhesion-dependent growth,
      it is important to know whether prevention of any one of these down-regulation
      events under conditions of adhesion deprivation is sufficient to prevent the G1
      arrest. To that end, sublines of Rat1 fibroblasts capable of expressing cyclin E,
      cyclin D1, or both in an inducible manner were used. Ectopic expression of cyclin
      D1 was sufficient to allow cells to enter S phase in an adhesion-independent
      manner. In contrast, cells expressing exogenous cyclin E at a level high enough
      to overcome the p27kip1-imposed inhibition of cyclin E-dependent kinase activity
      still arrested in G1 when deprived of adhesion. Moreover, expression of both
      cyclins D1 and E in the same cells did not confer any additional growth advantage
      upon adhesion deprivation compared to the expression of cyclin D1 alone.
      Exogenously expressed cyclin D1 was down-regulated under conditions of adhesion
      deprivation, despite the fact that it was expressed from a heterologous promoter.
      The ability of cyclin D1-induced cells to enter S phase in an adhesion
      independent manner disappears as soon as cyclin D1 proteins disappear. These
      results suggest that adhesion-dependent cell cycle progression is mediated
      through cyclin D1, at least in Rat1 fibroblasts.

PMID- 9271440
TI  - Dual requirement for a newly identified phosphorylation site in p70s6k.
AB  - The activation of p70s6k is associated with multiple phosphorylations at two sets
      of sites. The first set, S411, S418, T421, and S424, reside within the
      autoinhibitory domain, and each contains a hydrophobic residue at -2 and a
      proline at +1. The second set of sites, T229 (in the catalytic domain) and T389
      and S404 (in the linker region), are rapamycin sensitive and flanked by bulky
      aromatic residues. Here we describe the identification and mutational analysis of
      three new phosphorylation sites, T367, S371, and T447, all of which have a
      recognition motif similar to that of the first set of sites. A mutation of T367
      or T447 to either alanine or glutamic acid had no apparent effect on p70s6k
      activity, whereas similar mutations of S371 abolished kinase activity. Of these
      three sites and their surrounding motifs, only S371 is conserved in p70s6k
      homologs from Drosophila melanogaster, Arabidopsis thaliana, and Saccharomyces
      cerevisiae, as well as many members of the protein kinase C family. Serum
      stimulation increased S371 phosphorylation; unlike the situation for specific
      members of the protein kinase C family, where the homologous site is regulated by
      autophosphorylation, S371 phosphorylation is regulated by an external mechanism.
      Phosphopeptide analysis of S371 mutants further revealed that the loss of
      activity in these variants was paralleled by a block in serum-induced T389
      phosphorylation, a phosphorylation site previously shown to be essential for
      kinase activity. Nevertheless, the substitution of an acidic residue at T389,
      which mimics phosphorylation at this site, did not rescue mutant p70s6k activity,
      indicating that S371 phosphorylation plays an independent role in regulating
      intrinsic kinase activity.

PMID- 9271438
TI  - The von Hippel-Lindau tumor suppressor gene product interacts with Sp1 to repress
      vascular endothelial growth factor promoter activity.
AB  - The von Hippel-Lindau tumor suppressor gene (VHL) has a critical role in the
      pathogenesis of clear-cell renal cell carcinoma (RCC), as VHL mutations have been
      found in both von Hippel-Lindau disease-associated and sporadic RCCs. Recent
      studies suggest that vascular endothelial growth factor (VEGF) mRNA is
      upregulated in RCC- and von Hippel-Lindau disease-associated tumors. We have
      therefore assessed the effect of the VHL gene product on VEGF expression. VEGF
      promoter-luciferase constructs were transiently cotransfected with a wild-type
      VHL (wt-VHL) vector in several cell lines, including 293 embryonic kidney and RCC
      cell lines. wt-VHL protein inhibited VEGF promoter activity in a dose-dependent
      manner up to 5- to 10-fold. Deletion analysis defined a 144-bp region of the VEGF
      promoter necessary for VHL repression. This VHL-responsive element is GC rich and
      specifically binds the transcription factor Sp1 in crude nuclear extracts. In
      Drosophila cells, cotransfected VHL represses Sp1-mediated activation but not
      basal activity of the VEGF promoter. We next demonstrated in coimmunoprecipitates
      that VHL and Sp1 were part of the same complex and, by using a glutathione-S
      transferase-VHL fusion protein and purified Sp1, that VHL and Sp1 directly
      interact. Furthermore, endogenous VEGF mRNA levels were suppressed in permanent
      RCC cell lines expressing wt-VHL, and nuclear run-on studies indicated that VHL
      regulation of VEGF occurs at least partly at the transcriptional level. These
      observations support a new mechanism for VHL-mediated transcriptional repression
      via a direct inhibitory action on Sp1 and suggest that loss of Sp1 inhibition may
      be important in the pathogenesis of von Hippel-Lindau disease and RCC.

PMID- 9271442
TI  - Detection of interleukin-1 and interleukin-6 on cryopreserved bovine mammary
      epithelial cells in vitro.
AB  - This investigation was performed to determine whether primary cultures of mammary
      cells from lactating cows would sustain production of interleukin (IL)-1, IL-6,
      and tumor necrosis factor (TNF), and express mRNA for cytokines interleukin (IL)
      1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, interferon (INF)-tau, TNF-alpha, and
      granulocyte-macrophage colony-stimulating factor (GM-CSF) by the reverse
      transcription-polymerase chain reaction (RT-PCR) in vitro. Cryopreserved mammary
      epithelial cells collected from cows at 1 week post calving were plated in
      collagen-coated 24-well culture plates (250,000 cells/well). IL-1 and IL-6
      productions were measured using a A375 cell growth inhibition assay and a 7TD1
      hybridoma proliferation assay, respectively. Production of IL-1 was demonstrated
      in mammary epithelial cells cultured with unsupplemented medium, but was not
      produced by cells cultured in medium supplemented with fetal bovine serum. IL-6
      production in the conditioned medium was continued at steady level until day 14,
      whereas IL-6-like bioactivity was not detected in medium alone. TNF-like activity
      was not detectable in any experiments. This study also demonstrated the
      expression of mRNA for multiple cytokines including IL-1alpha, IL-1beta, IL-6, IL
      10, TNF-alpha, and GM-CSF by RT-PCR in mammary cell cultures. The results
      indicate that bovine mammary epithelial cells of lactating cows produce IL-1 and
      IL-6 and have gene expression for multiple cytokines. This in vitro model will be
      useful to investigate the function and regulation of IL-1 and IL-6 in the
      lactating mammary gland.

PMID- 9271441
TI  - Chicken MAR-binding protein ARBP is homologous to rat methyl-CpG-binding protein
      MeCP2.
AB  - Here, we describe the cloning and further characterization of chicken ARBP, an
      abundant nuclear protein with a high affinity for MAR/SARs. Surprisingly, ARBP
      was found to be homologous to the rat protein MeCP2, previously identified as a
      methyl-CpG-binding protein. A region spanning 125 amino acids in the N-terminal
      halves is 96.8% identical between chicken ARBP and rat MeCP2. A deletion mutation
      analysis using Southwestern and band shift assays identified this highly
      conserved region as the MAR DNA binding domain. Alignment of chicken ARBP with
      rat and human MeCP2 proteins revealed six trinucleotide amplifications generating
      up to 34-fold repetitions of a single amino acid. Because MeCP2 was previously
      localized to pericentromeric heterochromatin in mouse chromosomes, we analyzed
      the in vitro binding of ARBP to various repetitive sequences. In band shift
      experiments, ARBP binds to two chicken repetitive sequences as well as to mouse
      satellite DNA with high affinity similar to that of its binding to chicken
      lysozyme MAR fragments. In mouse satellite DNA, use of several footprinting
      techniques characterized two high-affinity binding sites, whose sequences are
      related to the ARBP binding site consensus in the chicken lysozyme MAR (5'-GGTGT
      3'). Band shift experiments indicated that methylation increased in vitro binding
      of ARBP to mouse satellite DNA two- to fivefold. Our results suggest that
      ARBP/MeCP2 is a multifunctional protein with roles in loop domain organization of
      chromatin, the structure of pericentromeric heterochromatin, and DNA methylation.

PMID- 9271443
TI  - Renal clearance of endogenous creatinine, urea, sodium, and potassium in normal
      cats and cats with chronic renal failure.
AB  - The renal clearance test was carried out in 6 normal male cats and 12 male cats
      with chronic renal failure. The average concentrations of creatinine (Cr), urea,
      sodium (Na), and potassium (K) in the serum of the cats with chronic renal
      failure were 5.09, 136.7 (mg/100 ml), 143.9 and 3.71 (mEq/l) respectively, and
      the specific gravity of urine was 1.009. The renal clearances of Cr, urea, Na,
      and K (ml/min/kg of body weight) were 2.639 +/- 0.217, 1.034 +/- 0.110, 0.024 +/-
      0.007 and 0.266 +/- 0.028, respectively in normal cats, and were 0.789 +/- 0.407,
      0.358 +/- 0.211, 0.095 +/- 0.084 and 0.872 +/- 0.204 in cats with chronic renal
      failure. Clearance of Cr and urea was significantly lower in cats with chronic
      renal failure than in normal cats, while the values of Na and K were
      significantly higher in cats with chronic renal failure. The glomerular
      filtration of Cr and urea and the urinary excretion of these 4 substances were
      significantly higher in cats with chronic renal failure. The tubular reabsorption
      rates of Na and K were significantly lower in cats with chronic renal failure
      compared to those in normal cats, but there was no significant difference in urea
      and creatinine.

PMID- 9271444
TI  - Efficacy of monotherapy with benazepril, an angiotensin converting enzyme
      inhibitor, in dogs with naturally acquired chronic mitral insufficiency.
AB  - Benazepril (BP), an angiotensin convertive enzyme inhibitor, was administered
      orally once daily for 4 weeks to 31 dogs with mild to moderate (NYHA functional
      classes II and III) congestive heart failure caused from mitral insufficiency
      (MI). There were no significant changes in clinical signs, electrocardiogram
      findings, radiographical observations and plasma biochemical results in 11 dogs
      treated with placebo for 4 weeks. In 31 dogs treated with BP, appetite increased,
      and mean scores of heart failure signs, such as activity, exercise tolerance,
      cough and respiratory effort, were significantly improved. No dog displays signs
      suggesting systemic hypotension. One dog died suddenly on the 26th day of
      treatment with BP. This dog had good vigor and appetite till the evening before
      the death, and cough and exercise tolerance had been gradually improving. The
      heart rate and ECG parameters of BP treated dogs did not change significantly,
      but length of long axis of the heart decreased. In plasma biochemical tests,
      plasma urea nitrogen (UN) levels did not change significantly, and plasma
      creatinine (CRE) levels increased slightly within the normal ranges during BP
      trial. Two dogs had higher plasma UN levels with slightly higher plasma CRE
      levels, but had normal general condition and other biochemical results. Plasma
      ACE activity decreased to 57.3% of pre-treatment level at 4 weeks after BP
      treatment. It is concluded that BP monotherapy was efficacious at least in dogs
      with relatively low grade congestive heart failure caused by MI.

PMID- 9271445
TI  - Seasonal changes in the immunolocalization of steroidogenic enzymes in the testes
      of the Japanese black bear (Ursus thibetanus japonicus).
AB  - Seasonal changes in sites of immunostaining of steroidogenic enzymes were
      examined in testes of the Japanese black bear, Ursus thibetanus japonicus. In
      addition, serum concentrations of testosterone and estradiol-17beta were
      investigated by radioimmunoassay, and the seasonal changes were compared with the
      results of immunostaining. On the basis of morphological observations of
      spermatogenic activity, the reproductive cycle was divided into five periods: an
      active period in May and June; a degenerative period in November; a resting
      period in January; an early-resumptive period in March; and a late-resumptive
      period in April. Serum concentrations of testosterone differed with season
      accompanied by differences in spermatogenic activity, with baseline levels in
      November and January, increasing levels in March and April, and high levels in
      May, and April and June of the next year. Immunoreactivities specific for
      cholesterol side-chain cleaving cytochrome P450, 17alpha-hydroxylase cytochrome
      P450 and 30-hydroxysteroid dehydrogenase (3beta HSD) were observed in Leydig
      cells throughout the year. Only the percentages of Leydig cells immunopositive
      for 3beta HSD exhibited seasonal differences that correlated with serum
      concentrations of testosterone. Aromatase cytochrome P450 (P450arom) was
      immunolocalized in Leydig and Sertoli cells throughout the year, in spermatids in
      May, and April and June of the next year and in myoid cells in January and March.
      The percentages of Leydig cells immunopositive for this enzyme increased in May,
      and January, March and June of the next year. On the other hand, no pattern of
      seasonal change in serum estradiol-17beta concentration was observed. These
      results suggest that 3beta HSD is a key enzyme in the regulation of the
      testosterone production in Leydig cells. Furthermore, estrogen derived from
      Leydig and myoid cells seems to play a role in the regulation of Leydig cells by
      negative feedback as a paracrine and/or autocrine mediator.

PMID- 9271446
TI  - Osteometrical and CT examination of the Japanese wolf skull.
AB  - The skulls of Japanese wolf (Canis hodophilax) were osteometrically examined and
      compared with those of Akita-Inu. The skull total length was not statistically
      different between two species. However, significant differences were demonstrated
      between two species in some ratios concerning the frontal bone. CT examination
      was carried out in the Japanese wolf skull. The data indicated that the frontal
      sinus is not be largely developed and compressed in the dorso-ventral direction
      in parasagittal area. The narrow frontal sinus fitted to external shape of the
      frontal bone. The cribriform plate had a well-developed complicated structure in
      a caudal part of the ethmoid bone. These data will be useful to examine the
      respiratory function and the olfactory sense in the Japanese wolf.

PMID- 9271447
TI  - In vivo replication of porcine reproductive and respiratory syndrome virus in
      swine alveolar macrophages and change in the cell population in bronchoalveolar
      lavage fluid after infection.
AB  - Replication of porcine reproductive and respiratory syndrome (PRRS) virus in
      swine alveolar macrophages (AM) and cell population in broncho-alveolar lavage
      fluid (BALF) obtained from PRRS virus-infected pigs were investigated. BALF
      samples were periodically collected from 6 pigs infected with PRRS virus and 3
      non-inoculated control pigs by means of fiber-optic bronchoscope between post
      inoculation day (PID) 0 and 56. The mean ratio of macrophages in BALF collected
      from infected group was 92.7 +/- 3.2% before inoculation and gradually decreased
      from PID 14. On the other hand, the ratio of lymphocytes was 4.8 +/- 3.2% before
      inoculation and increased from PID 21 and indicated 41.8 +/- 9.1% on PID 28.
      After that, they decreased gradually and that of macrophages correspondingly
      increased. The ratio of neutrophils maintained between 0.7% and 5.1%. The ratios
      of macrophages, lymphocytes and neutrophils collected from control group were
      almost stable through the examination. Intracellular PRRS virus antigens in AM
      were detected from PID 2 by indirect immunofluorescence assay (IIFA). PRRS virus
      was first isolated from BALF samples collected from inoculated group between PID
      2 and 49. From serum, virus was isolated between PID 2 and 21. Antibodies in sera
      measured by IIFA to PRRS virus were first detected on PID 14 and the antibody
      titer rose to 1:640 or 1:1,280. The results suggested that PRRS virus replicates
      in swine AM for a relatively long period.

PMID- 9271449
TI  - Relationship between degree of mitral protrusion assessed by use of B-mode
      echocardiography and degree of mitral regurgitation using an experimental model
      in dogs.
AB  - We studied the relationship between the degree of mitral protrusion and degree of
      mitral regurgitation in an experimental model in which the degree of mitral
      protrusion could be adjusted. The model was developed by dissecting the dorsal
      papillary muscle through a left atriotomy in 5 dogs and re-attaching the
      papillary muscle to the original site using a single mattress suture threading
      through the epicardium under cardiopulmonary bypass. By manipulating the suture
      from a position outside the epicardium, the degree of mitral protrusion could be
      adjusted. The long-axis view of the mitral valve was imaged by B-mode
      echocardiography with the transducer placed directly over the surface of the
      right ventricular outflow tract. The height (H) from the coaptation point or tip
      of the protruded cusp in relation to the mitral annular plane was measured as an
      index of mitral protrusion. Mitral regurgitation as a result of the mitral
      protrusion decreased the left ventricular systolic pressure, and increased the
      heart rate, mean left atrial pressure (LAPm), and ratio of left ventricular end
      diastolic dimension to body weight (LVEDD/BW). H was negatively correlated to
      LAPm and LVEDD/BW (r = -0.723 and -0.697, respectively). Our results indicated
      that H expresses not only the degree of mitral protrusion but also the degree of
      mitral regurgitation, and were in agreement with the previous findings obtained
      on dogs with spontaneous mitral regurgitation.

PMID- 9271448
TI  - Resistance to infection with mouse hepatitis virus (MHV) in the cell clones
      derived from persistently infected DBT cells with the JHM strain of MHV.
AB  - PiD-10 and piD-11 cells that have been established from persistently infected DBT
      cells with the JHM strain of MHV (JHMV) were resistant to infection with JHMV.
      There was no significant difference in the amount of adsorbed virus among piD-10,
      piD-11 and DBT cells. When an expression of mRNA of the MHV receptor in piD-10
      and piD-11 cells was analyzed by the RT-PCR method, no significant difference was
      observed in the intensities of the amplified products among piD-10, piD-11 and
      DBT cells. Treatment of virus-adsorbed cells with PEG, which induces fusion of
      the cellular membrane with the viral envelop, causes entry of virus particles
      into cells. There was no significant difference in the yields of virus between
      PEG-treated and PEG-untreated cells. The titers of infectious virus internalized
      into piD-10 and piD-11 cells were the same as those in DBT cells. When piD-10 and
      piD-11 cells were fused with PEG and infected with JHMV, the yields of infectious
      virion particles from the fused cells between piD-10 and piD-11 cells were
      significantly lower than those from the fused cells between DBT and piD-10 or piD
      11 cells. The present study showed that resistance of piD-10 and piD-11 cells to
      JHMV infection is not due to an inhibition of JHMV entry into the cells.

PMID- 9271450
TI  - Most probable numbers of enterotoxigenic Clostridium perfringens in intestinal
      contents of domestic livestock detected by nested PCR.
AB  - The incidence and numbers of enterotoxigenic Clostridium perfringens in the
      intestinal contents of cattle, swine and broiler chickens were determined and
      compared with those of total (enterotoxigenic and nonenterotoxigenic) C.
      perfringens. The method used for the enumeration of enterotoxigenic C.
      perfringens consisted of a combination of the most probable number (MPN) method
      and a nested polymerase chain reaction after enrichment culture of the sample.
      Enterotoxigenic C. perfringens was found in 26% (4.0 x 10-4.3 x 10(2) MPN/100 g),
      22% (4.0 x 10-2.3 x 10(3) MPN/100 g) and 40% (4.0 x 10-2.4 x 10(4) MPN/100 g) of
      intestinal contents of 50 head each of cattle, swine and broiler chickens,
      respectively. Whereas, total C. perfringens was found in 76% (9.0 x 10-7.5 x
      10(6) MPN/100 g), 44% (7.0 x 10-4.3 x 10(6) MPN/100 g) and 80% (4.3 x 10(2)-9.3 x
      10(7) MPN/100 g) of intestinal contents of 50 head each of cattle, swine and
      broiler chickens, respectively, by the conventional MPN method. In all cases,
      enterotoxigenic cells were not dominant in the population of C. perfringens: a
      small number of enterotoxigenic cells of C. perfringens co-existed with a large
      number of nonenterotoxigenic cells in the same sample. The ratios of
      enterotoxigenic C. perfringens cells to total C. perfringens cells were 1/10
      1/10(5).

PMID- 9271451
TI  - Effects of click intensity and frequency on the brain-stem auditory evoked
      potentials in the common marmoset (Callithrix jacchus).
AB  - Brain-stem auditory evoked potentials (BAEPs) were recorded in 20 common
      marmosets (Callithrix jacchus) to investigate the effects of click frequency up
      to 99 kHz, in consideration of the higher hearing range of the marmoset, and
      intensity on wave forms and peak latencies. According to the results of BAEP
      recordings at frequencies of 4, 32, and 99 kHz, the number of components recorded
      was affected by the stimulus intensity and the clicks at an intensity of 80 dB
      peak equivalent sound pressure level (pe SPL) had the maximum number of clear
      components. Therefore, it was indicated that click stimulations at an intensity
      of 80 dB pe SPL over a broad range of frequencies appears to be useful for
      recording the maximum number of components in marmosets and may increase the
      information obtainable from BAEPs. BAEP latencies were prolonged as the stimulus
      intensity decreased from 100 to 50 dB pe SPL. The effects of stimulus frequency
      on the wave latencies and amplitudes in response to 80 dB pe SPL at frequencies
      between 0.5 and 99 kHz revealed various changes: the amplitude of wave I
      increased at 16 and 32 kHz, but that of waves III and V increased at 4-8 and 64
      99 kHz. These increases in amplitudes of the waves may correlate with higher
      synchronous activity of the peripheral or central auditory pathways.

PMID- 9271452
TI  - Expression and cellular localization of inhibin alpha-subunit mRNA in equine
      fetal gonads.
AB  - The expression of inhibin alpha-subunit mRNA in equine fetal gonads during
      pregnancy (Days 90 to 300) was examined by means of Northern blot analysis. In
      all samples examined, a single species of transcript was detected at the size of
      1.5 kb. A digoxigenin-labeled antisense cRNA probe specific to equine inhibin
      alpha-subunit was synthesized and in situ hybridization analysis to locate the
      inhibin alpha-subunit mRNA positive cells was performed using frozen tissue
      sections of equine fetal ovary (day 150 of pregnancy) and equine fetal testis
      (day 180 of pregnancy). In the fetal ovary, positive cells were seen throughout
      the interstitial area but did not show any particular localization. In the fetal
      testis, on the other hand, the antisense cRNA hybridized almost exclusively to
      the interstitial cells surrounding developing seminiferous cords and Sertoli
      cells within the cords. Positive signals were also detected in a limited number
      of the interstitial cells located away from the cords. These results suggest that
      in equine fetal gonads, inhibin and/or inhibin alpha-subunit related molecules
      such as the monomeric form are produced and these molecules may have a
      paracrine/autocrine role within the gonads.

PMID- 9271453
TI  - Domon L, an immunopotentiating agent, acts as an NF-kappaB activator.
AB  - Domon L, a heat-treated component of gram-negative bacterium Achromobacter
      stenohalis, is used for the treatment of infectious diseases of animals. Here, we
      investigated the immunopotentiating potential of Domon L. In vitro studies showed
      that Domon L enhanced nitric oxide (NO) formation from murine macrophage RAW264.7
      cells in concert with interferon (IFN)-gamma. The effect of Domon L on NF-kappaB
      activation was investigated, in order to understand the molecular mechanisms of
      enhanced NO formation by Domon L. Domon L induced translocation of NF-kappaB to
      the nucleus in RAW264.7 cells. Induction of NF-kappaB dependent gene expression
      by Domon L was further confirmed using a transfectant containing an NF-kappaB
      luciferase reporter gene. In vivo injection of Domon L elevated both serum IL-6
      and mucoprotein, whose gene expression is partly under the control of NF-kappaB.
      The spleen cells of rats treated with Domon L produced much more NO when
      stimulated with LPS + IFN gamma than spleen cells of untreated rats. These
      results suggest that Domon L acts as an anti-infectious agent via NF-kappaB
      activation.

PMID- 9271454
TI  - Distribution of desmin and fibronectin in chick embryo gonad during testicular
      cord formation.
AB  - The distribution of desmin and fibronectin in the chick embryo gonad in and after
      sexual differentiation was investigated immunohistochemically. In the
      undifferentiated gonad (stage 27), fibronectin was detected in the dorsal
      mesentery, basement membrane and part of the parenchyma, while desmin was not
      recognized. After sexual differentiation (stages 31 to 34), desmin-positive cells
      gradually increased in number with the progress of development. They were
      obviously seen in developing interstitial regions between testicular cords.
      However, fibronectin was hardly observed at the same stages. At stage 37, desmin
      positive cells were present only in a part of the Leydig cells and myoid cells,
      while fibronectin was discontinuous in the basement membrane surrounding
      testicular cords. In addition, the expressions of desmin and fibronectin were
      simultaneously and adjacently recognized. These results suggest that myoid cells
      may produce fibronectin protein and that fibronectin mainly contributes to the
      formation of testicular cord basement membrane in chick embryos. Thus, the cell
      to-cell and cell-to-matrix interactions may be important in testicular
      morphogenesis of chick embryos.

PMID- 9271455
TI  - Serum apolipoprotein B-100 concentrations in healthy and diseased cattle.
AB  - The purpose of this study was to establish the normal range of serum
      apolipoprotein B-100 (APO B-100) concentration in clinically normal cattle, and
      to assess its abnormalities with clinical diseases. We measured the serum
      concentration of APO B-100 in cattle of varying ages, breeds and sex, maintained
      under normal field conditions. Blood samples were obtained from 735 apparently
      healthy cattle and 146 cows with various diseases. The concentration of serum APO
      B-100 in cattle was assayed by the single radial immunodiffusion method. The
      concentration of serum APO B-100 in healthy adult breeding bulls (mean +/- SD:
      Holstein; 101 +/- 46 microg/ml, Japanese Black; 106 +/- 46 microg/ml) was
      significantly (P<0.001) lower than that in cows (Holstein; 259 +/- 63, Japanese
      Black; 210 +/- 46 microg/ml), while that of APO B-100 in steers (Holstein; 290 +/
      86 microg/ml, Japanese Black; 302 +/- 90 microg/ml) was similar to the level in
      cows. The concentration of serum APO B-100 in cattle varied with sex and breed.
      APO B-100 concentration in cattle was decreased in association with metabolic
      disorders such as ketosis, displaced abomasum and fatty liver. From these
      results, it is assumed that the level of serum APO B-100 will be applied to
      diagnosis of metabolic diseases in cattle.

PMID- 9271456
TI  - Acute toxoplasmosis in squirrel monkeys.
AB  - Five cases of acute toxoplasmosis in caged squirrel monkeys (Saimiri sciureus)
      were reviewed. The early stages of systemic toxoplasmosis were present in all
      cases. In the liver, there were multiple foci of hepatocellular necrosis. The
      lung had diffuse interstitial pneumonia. Tachyzoites were mainly seen associated
      with lesions in the liver, lung, and spleen. Immunohistochemically, tachyzoites
      reacted with T. gondii antibody. Electron-microscopically, intracellular
      tachyzoite was surrounded by a thin wall and was in a membrane-bound
      parasitophorus vacuole.

PMID- 9271457
TI  - Diagnosis of quinolone-induced arthropathy in juvenile dogs by use of magnetic
      resonance (MR) imaging.
AB  - The present study was carried out to confirm whether arthropathy in juvenile dogs
      induced by ofloxacin, a new quinolone antibacterial agent, may be diagnosed by
      magnetic resonance (MR) imaging. Three-month-old male beagle dogs were orally
      administered ofloxacin at 20 mg/kg once daily for 7 consecutive days. On day 8,
      MR images were obtained with a 4.7-tesla (T) super-conductive high magnetic field
      strength unit. An irregular cartilage surface and dissecans changes in the distal
      femoral condyle were observed. These MR findings were essentially consistent with
      pathologic observation showing multifocal blisters on the articular cartilage
      with an increased amount of turbid synovial fluid in the joint. The results
      demonstrate that occurrence of ofloxacin arthropathy in juvenile dogs can be
      clearly diagnosed by use of MR imaging.

PMID- 9271458
TI  - Localization of neuropeptides in endocrine cells of the chicken thymus.
AB  - Interactions between endocrine cells and epithelial cells, mediated by
      neurotensin, have been proposed in the chicken thymus. In this study, other
      neuropeptide candidates acting as mediators in the chicken thymus were examined
      immunohistochemically. Endocrine cells being oval, elongated or triangular in
      shape were immunoreactive with antibodies against methionine-enkephalin,
      neuropeptide Y, substance P, and vasoactive intestinal peptide. These findings
      suggest that 4 neuropeptides may be involved in cell-to-cell interactions in the
      chicken thymus.

PMID- 9271459
TI  - Morphological change in tumor endothelial cells induced by natural-type human
      tumor necrosis factor.
AB  - The effects of natural-type human tumor necrosis factor (nh-TNF) on tumor
      endothelial cells of experimental brain tumors were investigated electron
      microscopically. Tumor vessels with hypertrophic endothelial cells were observed
      12 and 24 hr after an intralesional administration of 5,000 U of nh-TNF.
      Increased biosynthetic organelles such as the Golgi complex and rough endoplasmic
      reticulum were evident in the plump cytoplasms. These endothelial cells resembled
      those in high endothelial venules (HEV) functionally characterized by the high
      permeability of leukocytes. In addition, close interactions between these
      endothelial cells and leukocytes were observed. Our findings indicated that nh
      TNF could promote the morphological change in tumor endothelial cells into HEV
      like cells.

PMID- 9271460
TI  - Comparison of laboratory data in dogs with heartworm caval syndrome surviving and
      nonsurviving after surgical treatment.
AB  - Laboratory data in 47 dogs with caval syndrome (CS) surviving after surgical HW
      removal compared with those in 15 dogs with CS which died after the treatment.
      The number of HWs removed in surviving dogs was significantly greater than in
      nonsurviving dogs. The Ht value was significantly higher in nonsurviving dogs
      than in surviving dogs. Plasma enzyme activities ranged widely from normal to
      extremely high levels, and there were no significant differences in plasma enzyme
      activities between the surviving and nonsurviving dogs. Serum total protein, and
      plasma triglyceride, creatinine, glucose, calcium, sodium (Na) and chloride (Cl)
      levels were much similar between the HW-free and surviving dogs, but
      significantly different between the HW-free and nonsurviving dogs. Plasma urea
      nitrogen, uric acid and potassium levels were higher, and plasma Na and Cl levels
      were lower in nonsurviving dogs than in surviving dogs.

PMID- 9271461
TI  - Bradykinin-induced airway contraction in two lines of guinea pigs with
      congenitally different airway sensitivity.
AB  - The airway responsiveness to bradykinin (0.1, 1 and 10 microg/kg, i.v.) was
      examined in two lines of guinea pigs, BHS (bronchial hypersensitive) and BHR
      (bronchial hyposensitive) lines, with different airway sensitivity to inhalation
      of acetylcholine (ACh)-aerosol. Normal Hartley strain guinea pigs were used as a
      control group. The airway contraction was measured by recording intratracheal
      pressure (P[IT]) and respiratory airflow (V) under the condition of artificial
      ventilation in anesthetized guinea pigs. The results show airway responsiveness
      to bradykinin in BHS guinea pigs to be significantly greater than in BHR and
      normal Hartley strain guinea pigs.

PMID- 9271462
TI  - In vivo antitumor effect of cationic liposomes containing diphtheria toxin A
      chain gene on cells infected with bovine leukemia virus.
AB  - A plasmid pLTR-DT which contained a gene for diphtheria toxin A-chain (DT-A)
      under the control of the long terminal repeat (LTR) of bovine leukemia virus
      (BLV) (BLV-LTR) in the multicloning site of pUC-18 was entrapped in cationic
      liposomes composed of N-(alpha-trimethylammonioacetyl)-didodecyl-D-glutamate
      chloride (TMAG), dioleoyl phosphatidylethanolamine (DOPE) and dilauroyl
      phosphatidylcholine (DLPC) (1:2:2, molar ratio) (TMAG-liposome), and their
      antitumor effect on BLV-infected tumor cells was examined in vivo. The cationic
      TMAG-liposome containing pLTR-DT was successively injected into the tumor
      transplanted to nude mice. The growth of tumor was significantly inhibited by the
      injection of cationic TMAG-liposome containing pLTR-DT. On the other hand, TMAG
      liposome containing pUC18 plasmids showed no such effect. These results suggest
      that a DT-A expression plasmid under the control of BLV-LTR is highly toxic to
      the BLV-infected tumor cells, and that the cationic liposomes, such as TMAG
      liposome, may be efficient transfection reagent for BLV-infected tumor cells and
      can be utilized for DT-A gene delivery into BLV-infected tumor cells in vivo.

PMID- 9271469
TI  - IgE response in schistosomiasis japonica: characterization of a cercarial
      allergen in comparison with purified egg allergens.
AB  - The relationship between the cercarial allergen and two previously isolated egg
      allergens (J1, J2) of Schistosoma japonicum was examined especially in terms of
      the cross-reactivity between them. Semi-purified cercarial allergen (JAC) was
      obtained from the crude extract of S. japonicum cercariae by gel chromatography
      on Sephadex G-200. The apparent molecular weight of JAC was estimated
      approximately as 60-100 kDa. JAC could bind to Con A-Sepharose, indicating its
      glycoprotein nature. Three groups of BALB/c mice were immunized with JAC , J1 or
      J2 using A1(OH)3 as adjuvant, and the cross-reactivity of each anti-serum was
      examined by PCA. Anti-JAC, anti-J1 or anti-J2 serum was highly specific to the
      corresponding antigen. When IgE-ELISA of S. japonicum patient sera was performed
      using JAC, J1 or J2 as an antigen, the correlation between anti-J1 and anti-J2 (r
      = 0.78) was high, whereas the correlation between anti-JAC and anti-J1 (r = 0.27)
      or between anti-JAC and anti-J2 (r = 0.12) was low. These results suggest that
      most IgE epitopes on cercarial allergen are independent from those on egg
      allergens in S. japonicum.

PMID- 9271471
TI  - A cross-sectional study of helminths in rural scavenging poultry in Tanzania in
      relation to season and climate.
AB  - A cross-sectional study on the prevalence of helminths in rural scavenging
      poultry on six hundred adult chickens selected randomly from six villages in the
      Morogoro Region, Tanzania during the wet and the dry seasons, was conducted. The
      trachea and gastrointestinal tract of each bird were examined for the presence of
      parasites. All chickens were infected with one or several species of helminths,
      the average being 4.8 +/- 1.7 helminths per chicken during the wet season and 5.1
      +/- 1.8 during the dry season. A total of 29 different helminth species were
      shown in the trachea or the gastrointestinal tract. The following species were
      identified: Syngamus trachea (0.7% (wet season), 2% (dry season)); Gongylonema
      ingluvicola (6.3%, 17.7%); Tetrameres americana (54.3%, 60.3%); Dispharynx nasuta
      (0%, 2.7%); Acuaria hamulosa (8.3%, 19.3%); Ascaridia galli (28.3%, 32.3%);
      Heterakis gallinarum (74.0%, 78.7%); H. isolonche (18.7%, 5.0%); H. dispar
      (25.7%, 6.3%); Allodapa suctoria (40.0%, 52.0%); Subulura strongylina (3.3%,
      1.0%); Strongyloides avium (0.3%, 3.0%); Capillaria annulata (2.0%, 0.0%); C.
      contorta (9.0%, 1.0%); C. caudinflata (2.0%, 4.3%); C. obsignata (8.7%, 25.0%);
      C. anatis (4.0%, 9.0%); C. bursata (1.0%, 2.7%); Raillietina echinobothrida
      (41.3%, 46.3%); R. tetragona (25.3%, 21. 3%); R. cesticillus (8.7%, 2.7%);
      Choanotaenia infundibulum (0.0%, 3. 7%); Hymenolepis carioca (9.0%, 18.0%); H.
      cantaniana (48.0%, 43. 0%); Amoebotaenia cuneata (39.3%, 36.0%); Metroliasthes
      lucida (1.0%, 0.3%); Davainea proglottina (5.7%, 0.3%) and Polymorphus boschadis
      (0.3%, 0.0%). No trematodes were found. No correlation was found between season
      and prevalence, or season and mean worm burdens. Twelve helminths of the species
      recovered represent new local records.

PMID- 9271472
TI  - Life-cycle of Bothriocephalus claviceps, a specific parasite of eels.
AB  - The life-cycle of the tapeworm Bothriocephalus claviceps (Goeze, 1782) (Cestoda:
      Pseudophyllidea), a specific parasite of eels (Anguilla spp.), was studied under
      experimental conditions. It was demonstrated that the parasite completed its
      development within 4 months at the temperature range of 22-24 degrees C.
      Embryonic development was finished in 2 days at this temperature, when coracidia
      spontaneously hatched. The rate of their development was controlled by water
      temperature, with delayed formation of coracidia at lower temperatures (8 days at
      10-12 degrees C). At 2-4 and 6 degrees C, development did not take place but the
      eggs remained viable; at 33 degrees C the eggs died. The procercoids developed in
      copepods of the species Macrocyclops albidus, M. fuscus, Megacyclops viridis,
      Cyclops strenuus, C. vicinus and Acanthocyclops vernalis (Copepoda: Cyclopidae);
      their development was finished after 8-12 days at 22-24 degrees C. The definitive
      hosts, eels, acquired infection after ingestion of infected copepods; the
      prepatent period of the parasite was more than three months. Perch (Perca
      fluviatilis) and guppies (Poecilia reticulata) were shown to serve as paratenic
      hosts of the parasite; in guppies, the tapeworms survived up to 14 days after
      exposure and they developed similarly to tapeworms in the definitive host.

PMID- 9271473
TI  - Comparison of the post-parturient rise in faecal egg counts of indigenous and
      cross-bred ewes.
AB  - The breed differences in post-parturient rise (PPR) in faecal egg counts in
      lambing ewes of different breeds naturally infected with Haemonchus contortus
      were compared. The ewes of Nali, 50% Nali x 50% Russian Merino/Corriedale and
      37.5% Nali x 62.5% Russian Merino/Corriedale were treated with fenbendazole while
      ewes of the above three breeds as well as 25% Nali x 75% Russian
      Merino/Corriedale, were kept untreated. Observations from 3 weeks before lambing
      to 12 weeks post-lambing at weekly intervals revealed that in treated ewes, egg
      counts of Nali did not differ significantly with 50% Nali whereas 37.5% Nali had
      significantly higher egg counts than those of Nali and 50% Nali. In untreated
      ewes egg counts of 50% Nali were significantly higher than that of Nali on some
      occasions, while 25% Nali had significantly higher egg counts than the other
      three breeds. None of the ewes from the Nali breed showed signs of haemonchosis,
      whereas few lambing ewes of the three Nali crosses (50%, 37.5% and 25% Nali)
      showed signs of haemonchosis and one ewe of the latter breed died.

PMID- 9271474
TI  - Variation in the larval recovery of Toxocara canis from the murine brain:
      implications for behavioural studies.
AB  - The migratory pathway of Toxocara canis larvae was determined by infecting mice
      with a low, medium or high dose of embryonated T. canis eggs and determining
      numbers of larvae present in the brain, liver, lungs, kidneys and muscle on days
      5, 14 and 26 post infection. Variation was seen in the numbers of larvae recorded
      in the organs of mice which had received the same number of eggs and were at the
      same stage of infection. This variation was particularly marked in the brain
      indicating that, for the purposes of behavioural studies, the actual numbers of
      larvae found in the brain rather than the number assumed from the dose would have
      to be taken into account when analysing the behaviour of infected mice.

PMID- 9271475
TI  - The expulsion of Echinostoma trivolvis: worm kinetics and intestinal reactions in
      C3H/HeN mice treated with dexamethasone.
AB  - C3H/HeN mice were each infected with 40 Echinostoma trivolvis metacercarial cysts
      on day 0, given intramuscular injections of dexamethasone (DEX) daily for 30
      days, and necropsied on days 5, 8, 12, 15, 20 and 30 p. i. Control mice were each
      infected with 40 echinostome cysts on day 0, but were not treated with DEX and
      necropsied on the same days as the DEX-treated mice. DEX treatment caused an
      inhibition of worm expulsion and suppressed the increase in goblet cell numbers
      that peaked around day 12 p. i. in the untreated control mice. Increase in the
      number of mucosal mast cells and eosinophils in the control mice that peaked
      around day 15 and 12 p. i., respectively, was also suppressed by the DEX
      treatment. The mean body area of the worms from the DEX-treated mice was about
      the same as that of the control worms on day 5 p. i., and then significantly
      greater than the control worms on days 8 and 12 p. i. The worms in the treated
      mice continued to grow until the end of the experiment, on day 30 p. i. Enzyme
      linked immunosorbent assay (ELISA) showed that serum IgM from the treated and
      control mice increased from day 12 p. i., peaked on day 15 p. i., and then
      decreased. An IgM titre of the treated mice was slightly higher than that of the
      controls. No marked rise in IgG and IgA titres occurred throughout the experiment
      in both groups.

PMID- 9271478
TI  - Cellular immune response studies in bancroftian filariasis.
AB  - An attempt was made to identify the filarial specific antigens that are capable
      of inducing immune response in human filariasis. Lymphocytes were taken from
      three clinically defined groups living in an endemic area in Madras, namely
      microfilaraemic (MF) subjects with microfilariae in their blood smear without any
      clinical symptoms, chronic pathology (CP) individuals with lymphangitis or
      lymphadenitis in combination with a history of recurrent filarial fevers or
      lymphoedema, and endemic normals (EN) subjects without microfilariae nor any
      clinical symptoms of pathology. Lymphocytes from the three groups responded with
      no significant difference (P = 0.21) in their proliferative index to PPD and PHA,
      although lymphocytes from MF individuals showed significantly (P < 0.001) less
      proliferative index to Brugia malayi antigen (BMA) than the CP and EN subjects.
      This antigen specific cellular unresponsiveness seen in MF patients was not
      reversed by the addition of recombinant IL-1alpha, IL-1beta, and IFN-gamma, but
      the addition of sera from EN individuals seemed to restore this unresponsiveness
      (P < 0.001). The peripheral blood mononuclear cells from MF patients secreted
      more IL-1 in response to BMA induction than the same from CP and EN individuals.
      A 58 kDa recombinant protein isolated from a Wuchereria bancrofti genomic library
      (58 kDa) had mounted a higher proliferative response to lymphocytes from all
      three groups compared to BMA (P < 0.001) indicating the possible use of
      recombinant filarial protein to mount immunological responses in filarial
      patients.

PMID- 9271479
TI  - Valvular heart disease associated with fenfluramine-phentermine.
AB  - BACKGROUND: Fenfluramine and phentermine have been individually approved as
      anorectic agents by the Food and Drug Administration (FDA). When used in
      combination the drugs may be just as effective as either drug alone, with the
      added advantages of the need for lower doses of each agent and perhaps fewer side
      effects. Although the combination has not been approved by the FDA, in 1996 the
      total number of prescriptions in the United States for fenfluramine and
      phentermine exceeded 18 million. METHODS: We identified valvular heart disease in
      24 women treated with fenfluramine-phentermine who had no history of cardiac
      disease. The women presented with cardiovascular symptoms or a heart murmur. As
      increasing numbers of these patients with similar clinical features were
      identified, there appeared to be an association between these features and
      fenfluramine-phentermine therapy. RESULTS: Twenty-four women (mean [+/-SD] age,
      44+/-8 years) were evaluated 12.3+/-7.1 months after the initiation of
      fenfluramine-phentermine therapy. Echocardiography demonstrated unusual valvular
      morphology and regurgitation in all patients. Both right-sided and left-sided
      heart valves were involved. Eight women also had newly documented pulmonary
      hypertension. To date, cardiac surgical intervention has been required in five
      patients. The heart valves had a glistening white appearance. Histopathological
      findings included plaque-like encasement of the leaflets and chordal structures
      with intact valve architecture. The histopathological features were identical to
      those seen in carcinoid or ergotamine-induced valve disease. CONCLUSIONS: These
      cases arouse concern that fenfluramine-phentermine therapy may be associated with
      valvular heart disease. Candidates for fenfluramine-phentermine therapy should be
      informed about serious potential adverse effects, including pulmonary
      hypertension and valvular heart disease.

PMID- 9271480
TI  - Invasive infections due to a fish pathogen, Streptococcus iniae. S. iniae Study
      Group.
AB  - BACKGROUND: Streptococcus iniae is a pathogen in fish, capable of causing
      invasive disease and outbreaks in aquaculture farms. During the winter of 1995
      1996 in the greater Toronto area there was a cluster of four cases of invasive S.
      iniae infection in people who had recently handled fresh, whole fish from such
      farms. METHODS: We conducted a prospective and retrospective community-based
      surveillance for cases of S. iniae infection in humans. To obtain a large sample
      of isolates, we studied cultures obtained from the surface of fish from
      aquaculture farms. Additional isolates were obtained from the brains of infected
      tilapia (oreochromis species). All the isolates were characterized by pulsed
      field gel electrophoresis (PFGE). RESULTS: During one year, our surveillance
      identified a total of nine patients with invasive S. iniae infection (cellulitis
      of the hand in eight and endocarditis in one). All the patients had handled live
      or freshly killed fish, and eight had percutaneous injuries. Six of the nine fish
      were tilapia, which are commonly used in Asian cooking. Thirteen additional S.
      iniae isolates (2 from humans and 11 from infected tilapia) were obtained from
      normally sterile sites. The isolates from the nine patients were
      indistinguishable by PFGE and were highly related to the other clinical isolates.
      There was substantial genetic diversity among the 42 surveillance isolates from
      the surface of fish, but in 10 isolates the PFGE patterns were identical to those
      from the patients with S. iniae infection. CONCLUSIONS: S. iniae can produce
      invasive infection after skin injuries during the handling of fresh fish grown by
      aquaculture. We identified a clone of S. iniae that causes invasive disease in
      both humans and fish.

PMID- 9271481
TI  - Estrogen and progestin compared with simvastatin for hypercholesterolemia in
      postmenopausal women.
AB  - BACKGROUND: Postmenopausal estrogen therapy has favorable effects on serum
      lipoproteins in women with normal serum lipid levels, but the effect of combined
      estrogen and progestin therapy on lipoproteins in women with hypercholesterolemia
      has not been determined, nor has it been directly compared with the effect of
      conventional lipid-lowering therapy. METHODS: In a randomized crossover trial, we
      studied 58 postmenopausal women with fasting serum total cholesterol levels
      greater than 250 mg per deciliter. Each woman received simvastatin (10 mg daily)
      for eight weeks and postmenopausal hormone therapy (up to 1.25 mg of conjugated
      equine estrogens daily, along with 5 mg of medroxyprogesterone acetate daily) for
      eight weeks, with an eight-week washout period between the two treatment phases.
      RESULTS: At base line, the mean (+/-SD) cholesterol values were as follows: total
      cholesterol, 305+/-39 mg per deciliter; high-density lipoprotein (HDL)
      cholesterol, 62+/-19 mg per deciliter; and low-density lipoprotein (LDL)
      cholesterol, 217+/-39 mg per deciliter. For total cholesterol, the mean decrease
      with hormone therapy was 14 percent (95 percent confidence interval, 11 to 16
      percent) and the mean decrease with simvastatin was 26 percent (95 percent
      confidence interval, 23 to 29 percent). For LDL cholesterol, the mean decrease
      was 24 percent (95 percent confidence interval, 20 to 28 percent) with hormone
      therapy and 36 percent (95 percent confidence interval, 32 to 40 percent) with
      simvastatin. The effect of simvastatin was significantly greater than that of
      hormone therapy (P<0.001). HDL cholesterol increased similarly with hormone
      therapy (mean increase, 7 percent; 95 percent confidence interval, 2 to 12
      percent) and simvastatin (mean increase, 7 percent; 95 percent confidence
      interval, 4 to 10 percent). Triglyceride levels increased with hormone therapy
      (mean increase, 29 percent; 95 percent confidence interval, 15 to 42 percent) but
      decreased with simvastatin (mean decrease, 14 percent; 95 percent confidence
      interval, 8 to 20 percent). Lp(a) lipoprotein decreased with hormone therapy
      (mean decrease, 27 percent; 95 percent confidence interval, 20 to 34 percent),
      but not with simvastatin. CONCLUSIONS: In postmenopausal women with
      hypercholesterolemia, therapy with estrogen plus progestin has beneficial effects
      on lipoprotein levels. Hormone therapy may be an effective alternative to
      treatment with simvastatin, especially in women with normal triglyceride levels.

PMID- 9271482
TI  - Fatal pulmonary hypertension associated with short-term use of fenfluramine and
      phentermine.

PMID- 9271483
TI  - Delayed puberty and hypogonadism caused by mutations in the follicle-stimulating
      hormone beta-subunit gene.

PMID- 9271484
TI  - Images in clinical medicine. Mycobacterium marinum infection of the hand.

PMID- 9271485
TI  - Injury prevention. Second of two parts.

PMID- 9271487
TI  - Diet pills redux.

PMID- 9271486
TI  - The Oregon Health Plan--lessons for the nation. First of two parts.

PMID- 9271488
TI  - Biomedical research and insider trading.

PMID- 9271490
TI  - Biochemical and spectroscopic characterization of two new cytochromes isolated
      from Desulfuromonas acetoxidans.
AB  - The multimeric cytochromes described to date in sulfate- and sulfur-reducing
      bacteria are associated with diverse respiratory modes involving the use of
      elemental sulfur or oxidized sulfur compounds as terminal acceptors. They exhibit
      no structural similarity with the other cytochrome c classes and are
      characterized by a bis-histidinyl axial iron coordination and low redox
      potentials. We have purified two new cytochromes c with markedly different
      molecular masses (10 000 and 50 000) from the bacterium Desulfuromonas
      acetoxidans, which uses anaerobic sulfur respiration as its sole energy source.
      The characterization by electrochemistry and optical and EPR spectroscopies
      revealed the cytochrome c (Mr = 10 000) to be the first monohemic cytochrome c
      exhibiting a bis-histidinyl axial coordination and a low redox potential (-220
      mV). The cytochrome c (Mr = 50 000) contains four hemes of low potential (-200, 
      210, -370, and -380 mV) with the same axial coordination. The N-terminal amino
      acid sequences were compared with that of the trihemic cytochrome c7, previously
      described in D. acetoxidans and which is related to tetrahemic cytochrome c3 from
      sulfate reducing bacteria. Some homology was found between cytochrome c (Mr = 10
      000) and cytochrome c7. Both D. acetoxidans cytochromes c are located in the
      periplasmic space and their biochemical and spectroscopic properties indicate
      that they belong to the class III cytochromes.

PMID- 9271491
TI  - Characterization of the inducible nitric oxide synthase oxygenase domain
      identifies a 49 amino acid segment required for subunit dimerization and
      tetrahydrobiopterin interaction.
AB  - The oxygenase domain of inducible NO synthase (residues 1-498, iNOSox) is the
      enzyme's catalytic center. Its active form is a homodimer that contains heme and
      tetrahydrobiopterin (H4biopterin) and binds l-arginine [Ghosh, D. K., & Stuehr,
      D. J. (1995) Biochemistry 34, 801]. To help identify protein residues involved in
      prosthetic group and dimeric interaction, we expressed H4biopterin-free iNOSox in
      Escherichia coli. The iNOSox was 80% dimeric but contained a low-spin heme iron
      that bound DTT as a sixth ligand. The iNOSox bound H4biopterin or L-arginine with
      high affinity, which displaced DTT from the heme and caused spectral changes
      consistent with a closing up of the heme pocket. The H4biopterin-replete iNOSox
      could catalyze conversion of Nomega-hydroxyarginine to citrulline and NO in a
      H2O2-supported reaction. Limited trypsinolysis of the H4biopterin-free iNOSox
      dimer cut the protein at a single site in its N-terminal region (K117).
      H4biopterin protected against the cleavage whereas l-arginine did not. The
      resulting 40 kDa protein contained thiol-ligated low-spin heme, was monomeric,
      catalytically inactive, showed no capacity to bind H4biopterin or l-arginine, and
      did not dimerize when provided with these molecules, indicating that residues 1
      117 were important for iNOSox dimerization and H4biopterin/l-arginine
      interaction. A deletion mutant missing residues 1-114 was partially dimeric but
      otherwise identical to the 40 kDa protein regarding its spectral and catalytic
      properties and inability to respond to l-arginine and H4biopterin, whereas a
      deletion mutant missing residues 1-65 was equivalent to wild-type iNOSox,
      narrowing the region of importance to amino acids 66-114. Mutation of a conserved
      cysteine in this region (C109A) decreased H4biopterin affinity without
      compromising iNOSox dimeric structure, L-arginine binding, or catalytic function.
      These results suggest that residues 66-114 of iNOSox are involved in productive
      H4biopterin interaction and subunit dimerization. H4biopterin binding appears to
      stabilize the protein structure in this region, and through doing so activates
      iNOS for NO synthesis.

PMID- 9271492
TI  - A cysteine-3 to serine mutation of the G-protein Gi1 alpha abrogates functional
      activation by the alpha 2A-adrenoceptor but not interactions with the beta gamma
      complex.
AB  - Pertussis toxin-resistant (C351G) and also palmitoylation-negative (C3S/C351G),
      myristoylation-negative (G2A/C351G) and combined acylation-negative
      (G2A/C3S/C351G) forms of the G-protein Gi1 alpha were expressed in COS-7 cells
      along with the porcine alpha 2A-adrenoceptor. G2A/C3S/C351G Gi1 alpha and
      G2A/C351G Gi1 alpha were largely cytosolic and failed to interact with the
      agonist-occupied alpha 2A-adrenoceptor in membrane preparations. In contrast,
      C351G Gi1 alpha was almost entirely particulate and the alpha 2-adrenoceptor
      agonist UK14304 caused a marked stimulation of its GTPase activity and binding of
      [35S]GTP gamma S which was not prevented by pertussis toxin treatment of the
      cells. C3S/C351G Gi1 alpha was present in both the particulate and cytosolic
      fractions but the GTPase activity of the membrane bound fraction was only
      slightly activated by the alpha 2A-adrenoceptor. Coexpression of C3S/C351G Gi1
      alpha and the alpha 2A-adrenoceptor along with beta 1 and gamma 2 subunits
      increased the P2 membrane complement of the alpha subunit and increased
      substantially the ratio of membrane bound to cytosolic protein. However, this
      also failed to allow marked stimulation of high-affinity GTPase activity by the
      alpha 2A-adrenoceptor despite the increased proportion of G-protein in the P2
      membrane fraction. Despite the low fractional activation of C3S/C351G Gi1 alpha
      by the alpha 2A-adrenoceptor compared to C351G Gi1 alpha, the palmitoylation
      resistant G-protein caused a marked reduction in pertussis toxin-resistant,
      agonist (UK14304)-mediated stimulation of adenylyl cyclase activity. UK14304
      caused the same degree of effect on adenylyl cyclase activity in pertussis toxin
      treated cells following transfection of the same amounts of C351G Gi1 alpha and
      C3S/C351G Gi1 alpha, as both appear to act to sequester beta gamma subunits. By
      contrast, neither G2A/C351G Gi1 alpha nor G2A/C3S/C351G Gi1 alpha resulted in
      effective regulation of adenylyl cyclase activity.

PMID- 9271493
TI  - Effect of n-alkanols on lipid bilayer hydration.
AB  - The effect of a homologous series of aliphatic n-alkanols on the presence of
      water within the head group and acyl chain region of lipid bilayers was
      investigated using time-resolved fluorescence spectroscopy according to a
      previously published approach [Ho, C., Slater, S. J., & Stubbs, C. D. (1995)
      Biochemistry 34, 6188-6195]. Upon addition of n-alkanols to phosphatidylcholine
      bilayers the fluorescence lifetime of N-[5-(dimethylamino)naphthalene-1
      sulfonyl]dipalmitoylphosphatidyleth anolamine (dansyl-PE) decreased, indicative
      of an increased water content within the head group region, the effect being a
      linear function of n-alkanol chain length (C1-C8), based on the total n-alkanol
      concentration. The fluorescence lifetimes of 1-palmitoyl-2-[[2-[4-(6-phenyl-trans
      1,3, 5-hexatrienyl)phenyl]ethyl]carbonyl]-3-sn-phosphatidylcholine (DPH-PC) and N
      [[4-(6-phenyl-1,3, 5-hexatrienyl)phenyl]propyl]trimethylammonium p
      toluenesulfonate (TMAP-DPH), and the fluorescence intensity ratio of the latter
      in D2O compared to that in H2O, were used to probe the level of water in the acyl
      chain region. There was a decrease in the lifetime and an increase in the D2O/H2O
      fluorescence intensity ratio upon addition of short-chain n-alkanols (C1-C3),
      suggestive of increased water content. By contrast, long-chain n-alkanols (C4-C8)
      increased the lifetime and decreased the ratio, suggestive of decreased water
      content. Acyl chain order, determined from DPH-PC fluorescence anisotropy, was
      decreased by all n-alkanols, indicating that the effects were not probe
      dependent. The effects of short- and long-chain n-alkanols on the fluorescence
      lifetime of the tryptophans of gramicidin, incorporated into phosphatidylcholine
      bilayers as a model membrane protein, were similar to those obtained with TMAP
      DPH and DPH-PC; ethanol decreased and hexanol increased the lifetime. Thus the
      effect of n-alkanols and general anesthetics on changes in the amount of water
      that may be accommodated within the acyl chain region of the bilayer is not
      predictable on the basis of the magnitude of effects on head group region or acyl
      chain order/fluidity.

PMID- 9271494
TI  - Kinetic characterization of the strand separation ("helicase") activity of the
      DNA packaging enzyme from bacteriophage lambda.
AB  - Bacteriophage lambda is assembled from preformed viral capsids (proheads), tails,
      and genomes that are excised from a concatemeric DNA precursor. The enzyme
      responsible for insertion of the genome into the precapsid is known as terminase.
      This enzyme possesses site-specific endonuclease, ATPase, and DNA strand
      separation ("helicase") catalytic activities, which work in concert to excise and
      package a single viral genome during phage assembly. We have previously
      characterized the endonuclease [Tomka, M. A., & Catalano, C. E. (1993) J. Biol.
      Chem. 268, 3056-3065] and ATPase [Tomka, M. A., & Catalano, C. E. (1993)
      Biochemistry 32, 11992-11997] catalytic activities of lambda terminase and
      present here similar studies on the strand separation activity of the enzyme.
      Strand separation requires terminase, divalent metal, and adenosine nucleotides
      with a hydrolyzable beta,gamma-phosphate bond. Two apparent binding sites for ATP
      mediated strand separation were identified, one of which appears to be distinct
      from the high- and low-affinity sites previously observed for ATP hydrolysis
      [Hwang, Y., Catalano, C. E., & Feiss, M. (1995) Biochemistry 35, 2796-2803]. Salt
      stimulates the reaction at low concentrations but is strongly inhibitory at
      elevated concentrations, presumably due to impaired DNA binding. The above
      results are identical with either a complex DNA mixture (a nicked, annealed DNA
      duplex in the presence of excess nonspecific DNA) or a purified DNA substrate;
      however, a kinetic analysis of the reaction revealed that the observed rate was
      approximately 5-fold greater with the purified DNA substrate. Moreover, while
      Escherichia coli integration host factor (IHF) stimulates terminase-mediated
      strand separation with both substrates, the observed stimulation is more
      pronounced with the complex DNA mixture (10-fold rate increase) than the purified
      DNA substrate (5-fold rate increase). Our data are consistent with a model where
      IHF binding to the terminase assembly site forms a binary protein.DNA complex
      readily distinguishable from bulk DNA. The implications of these results to the
      process of DNA packaging in bacteriophage lambda are discussed.

PMID- 9271495
TI  - Mechanism of action of fotemustine, a new chloroethylnitrosourea anticancer
      agent: evidence for the formation of two DNA-reactive intermediates contributing
      to cytotoxicity.
AB  - Methyl excision repair deficient human tumor cells (Mer-) were found to be
      hypersusceptible to killing by the antimelanoma agent fotemustine (FM)
      implicating alkylation of O6 guanine as the major contributor to toxicity.
      Preincubation of the drug in aqueous solution for 5 min resulted in an immediate
      reduction in cytotoxicity (35-50%), in vitro DNA alkylation (31%), and DNA
      interstrand cross-linking (40%) followed by a second reaction with considerably
      slower kinetics. Electrospray ionisation mass spectrometry (ESI-MS) showed that
      in aqueous solution FM rearranged rapidly to form either a metastable tautomer or
      decomposed to form a highly reactive diazohydroxide (t1/2 < 2 min). These results
      suggest the presence of two DNA-reactive species relevant to biological activity.
      Coincubation of ellagic acid (an inhibitor of O6-guanine alkylation) with FM
      inhibited in vitro ISC, suggesting that the O6-chloroethyl lesion is the
      predominant cause of the cross-link. On the basis of these findings, we propose
      that FM breaks down to form a short-lived intermediate, 2
      chloroethyldiazohydroxide, which rapidly generates O6-guanine lesions responsible
      for the drug's initial activity and a long lived iminol tautomer responsible for
      the remaining O6 guanine alkylation and cytotoxicity.

PMID- 9271496
TI  - Mapping features of HIV-1 integrase near selected sites on viral and target DNA
      molecules in an active enzyme-DNA complex by photo-cross-linking.
AB  - The virally encoded integrase protein carries out retroviral integration, and to
      do so, it must make specific interactions with both viral and target DNA
      sequences. The retroviral integrase has three domains: an amino-terminal region
      of about 50 amino acids that contains a zinc finger-like motif, a tightly folded,
      phylogenetically conserved core domain that contains the active site, and a
      carboxy-terminal domain that can bind DNA in a nonspecific manner. The complete
      roles of the amino- and carboxyl-terminal domains have not yet been determined,
      but they appear to participate in multimerization and nonspecific or target DNA
      binding, respectively. The number and identity of integrase's DNA binding sites
      have been difficult to determine by conventional mutagenesis studies. In this
      report, we describe a photo-cross-linking approach to address these issues. Our
      findings suggest that HIV-1 integrase contacts with conserved features of the
      viral DNA end are likely to be mediated by residues in two peptides within the
      conserved core domain. Additional cross-links were seen between viral DNA and the
      carboxy-terminal DNA binding domain. Numerous sites in integrase, including
      peptides in each of the three domains, could be cross-linked to target DNA
      features. Integrase is known to function as a multimer, and it remains to be
      determined which specific contacts are in cis or trans with respect to the active
      site.

PMID- 9271497
TI  - Crystal structure of Tritrichomonas foetus inosine-5'-monophosphate dehydrogenase
      and the enzyme-product complex.
AB  - Inosine-5'-monophosphate dehydrogenase (IMPDH) is an attractive drug target for
      the control of parasitic infections. The enzyme catalyzes the oxidation of
      inosine monophosphate (IMP) to xanthosine monophosphate (XMP), the committed step
      in de novo guanosine monophosphate (GMP) biosynthesis. We have determined the
      crystal structures of IMPDH from the protozoan parasite Tritrichomonas foetus in
      the apo form at 2.3 A resolution and the enzyme-XMP complex at 2.6 A resolution.
      Each monomer of this tetrameric enzyme is comprised of two domains, the largest
      of which includes an eight-stranded parallel beta/alpha-barrel that contains the
      enzyme active site at the C termini of the barrel beta-strands. A second domain,
      comprised of residues 102-220, is disordered in the crystal. IMPDH is expected to
      be active as a tetramer, since the active site cavity is formed by strands from
      adjacent subunits. An intrasubunit disulfide bond, seen in the crystal structure,
      may stabilize the protein in a less active form, as high concentrations of
      reducing agent have been shown to increase enzyme activity. Disorder at the
      active site suggests that a high degree of flexibility may be inherent in the
      catalytic function of IMPDH. Unlike IMPDH from other species, the T. foetus
      enzyme has a single arginine that is largely responsible for coordinating the
      substrate phosphate in the active site. This structural uniqueness may facilitate
      structure-based identification and design of compounds that specifically inhibit
      the parasite enzyme.

PMID- 9271498
TI  - Mechanistic roles of tyrosine 149 and serine 124 in UDP-galactose 4-epimerase
      from Escherichia coli.
AB  - Synthesis and overexpression of a gene encoding Escherichia coli UDP-galactose 4
      epimerase and engineered to facilitate cassette mutagenesis are described.
      General acid-base catalysis at the active site of this epimerase has been studied
      by kinetic and spectroscopic analysis of the wild-type enzyme and its
      specifically mutated forms Y149F, S124A, S124V, and S124T. The X-ray crystal
      structure of Y149F as its abortive complex with UDP-glucose is structurally
      similar to that of the corresponding wild-type complex, except for the absence of
      the phenolic oxygen of Tyr 149. The major effects of mutations are expressed in
      the values of kcat and kcat/Km. The least active mutant is Y149F, for which the
      value of kcat is 0.010% of that of the wild-type epimerase. The activity of S124A
      is also very low, with a kcat value that is 0.035% of that of the native enzyme.
      The values of Km for Y149F and S124A are 12 and 21% of that of the wild-type
      enzyme, respectively. The value of kcat for S124T is about 30% of that of the
      wild-type enzyme, and the value of Km is similar to that of the native enzyme.
      The reactivities of the mutants in UMP-dependent reductive inactivation by
      glucose are similarly affected, with kobs being decreased by 6560-, 370-, and 3.4
      fold for Y149F, S124A, and S124T, respectively. The second-order rate constants
      for reductive inactivation by NaBH3CN, which does not require general base
      catalysis, are similar to that for the native enzyme in the cases of S124A,
      S124T, and S124V. However, Y149F reacts with NaBH3CN 12-20-fold faster than the
      wild-type enzyme at pH 8.5 and 7.0, respectively. The increased rate for Y149F is
      attributed to the weakened charge-transfer interaction between Phe 149 and NAD+,
      which is present with Tyr 149 in the wild-type enzyme. The charge-transfer band
      is present in the serine mutants, and its intensity at 320 nm is pH-dependent.
      The pH dependencies of A320 showed that the pKa values for Tyr 149 are 6.08 for
      the wild-type epimerase, 6.71 for S124A, 6.86 for S124V, and 6.28 for S124T. The
      low pKa value for Tyr 149 is attributed mainly to the positive electrostatic
      field created by NAD+ and Lys 153 (4.5 kcal mol-1) and partly to hydrogen bonding
      with Ser 124 (1 kcal mol-1). The pKa of Tyr 149 is the same as the kinetic pKa
      for the Bronsted base that facilitates hydride transfer to NAD+. We concluded
      that Tyr 149 provides the driving force for general acid-base catalysis, with Ser
      124 playing an important role in mediating proton transfer.

PMID- 9271499
TI  - Molecular structures of the S124A, S124T, and S124V site-directed mutants of UDP
      galactose 4-epimerase from Escherichia coli.
AB  - UDP-galactose 4-epimerase plays a critical role in sugar metabolism by catalyzing
      the interconversion of UDP-galactose and UDP-glucose. Originally, it was assumed
      that the enzyme contained a "traditional" catalytic base that served to abstract
      a proton from the 4'-hydroxyl group of the UDP-glucose or UDP-galactose
      substrates during the course of the reaction. However, recent high-resolution X
      ray crystallographic analyses of the protein from Escherichia coli have
      demonstrated the lack of an aspartate, a glutamate, or a histidine residue
      properly oriented within the active site cleft for serving such a functional
      role. Rather, the X-ray crystallographic investigation of the epimerase.NADH.UDP
      glucose abortive complex from this laboratory has shown that both Ser 124 and Tyr
      149 are located within hydrogen bonding distance to the 4'- and 3'-hydroxyl
      groups of the sugar, respectively. To test the structural role of Ser 124 in the
      reaction mechanism of epimerase, three site-directed mutant proteins, namely
      S124A, S124T, and S124V, were constructed and crystals of the S124A.NADH.UDP,
      S124A.NADH.UDP-glucose, S124T. NADH.UDP-glucose, and S124V.NADH.UDP-glucose
      complexes were grown. All of the crystals employed in this investigation belonged
      to the space group P3221 with the following unit cell dimensions: a = b = 83.8 A,
      c = 108.4 A, and one subunit per asymmetric unit. X-ray data sets were collected
      to at least 2.15 A resolution, and each protein model was subsequently refined to
      an R value of lower than 19.0% for all measured X-ray data. The investigations
      described here demonstrate that the decreases in enzymatic activities observed
      for these mutant proteins are due to the loss of a properly positioned hydroxyl
      group at position 124 and not to major tertiary and quaternary structural
      perturbations. In addition, these structures demonstrate the importance of a
      hydroxyl group at position 124 in stabilizing the anti conformation of the
      nicotinamide ring as observed in the previous structural analysis of the
      epimerase.NADH. UDP complex.

PMID- 9271500
TI  - Crystal structures of the inactive D30N mutant of feline immunodeficiency virus
      protease complexed with a substrate and an inhibitor.
AB  - Crystal structures of complexes of a D30N mutant of feline immunodeficiency virus
      protease (FIV PR) complexed with a statine-based inhibitor (LP-149), as well as
      with a substrate based on a modification of this inhibitor (LP-149S), have been
      solved and refined at resolutions of 2.0 and 1.85 A, respectively. Both the
      inhibitor and the substrate are bound in the active site of the mutant protease
      in a similar mode, which also resembles the mode of binding of LP-149 to the
      native protease. The carbonyl oxygen of the scissile bond in the substrate is not
      hydrated and is located within the distance of a hydrogen bond to an amido
      nitrogen atom from one of the two asparagines in the active site of the enzyme.
      The nitrogen atom of the scissile bond is 3.25 A from the conserved water
      molecule (Wat301). A model of a tetrahedral intermediate bound to the active site
      of the native enzyme was built by considering the interactions observed in all
      three crystal structures of FIV PR. Molecular dynamics simulations of this model
      bound to native wild-type FIV PR were carried out, to investigate the final
      stages of the catalytic mechanism of aspartic proteases.

PMID- 9271501
TI  - NMR structure of a protein kinase C-gamma phorbol-binding domain and study of
      protein-lipid micelle interactions.
AB  - Classical protein kinase C (PKC) family members are activated by the binding of
      various ligands to one of several cysteine-rich domains of the enzyme. The
      natural agonist, diacylglycerol (DAG), and the natural product superagonist,
      phorbol dibutyrate (PDB), activate the enzyme to produce wide-ranging
      physiological effects. The second cysteine-rich (Cys2) domain of rat brain PKC
      gamma was expressed and labeled with 15N and 13C, and the solution structure was
      determined to high resolution using multidimensional heteronuclear NMR methods.
      The phorbol binding site was identified by titrating this domain with phorbol
      12,13-dibutyrate (PDB) in the presence of organic cosolvents. Titrations of this
      domain with lipid micelles, in the absence and presence of phorbols, indicate
      selective broadening of some resonances. The observed behavior indicates
      conformational exchange between bound and free states upon protein-micelle
      interaction. The data also suggest that half of the domain, including the phorbol
      site and one of the zinc sites, is capable of inserting into membranes.

PMID- 9271502
TI  - Mechanism of the synergistic end-product regulation of Bacillus subtilis
      glutamine phosphoribosylpyrophosphate amidotransferase by nucleotides.
AB  - De novo purine nucleotide synthesis is regulated, at least in part, by end
      product inhibition of glutamine PRPP amidotransferase. An important feature of
      this inhibition is the fact that certain synergistic nucleotide pairs give more
      than additive inhibition. The physiological importance of synergism is in
      amplifying regulation by the adenine and guanine nucleotide end products of de
      novo synthesis. Using a new method to quantitate synergism, ADP plus GMP were
      confirmed [Meyer, E., and Switzer, R. L. (1978) J. Biol. Chem. 254, 5397-5402] to
      give strong synergistic inhibition of Bacillus subtilis glutamine PRPP
      amidotransferase. An X-ray structure of the ternary enzyme.ADP.GMP complex
      established that ADP binds to the allosteric A site and GMP to the catalytic C
      site. GMP increased the binding affinity of ADP for the A site by approximately
      20-fold. Synergism results from a specific nucleotide-nucleotide interaction that
      is dependent upon a nucleoside diphosphate in the A site and a nucleoside
      monophosphate in the C site. Furthermore, synergism is enhanced by the
      competition between nucleotide inhibitor and PRPP substrate for the C site.
      Purine base specificity results from a backbone carbonyl interaction of Lys305'
      with the 6-NH2 group of adenine in the A site and a Ser347 Ogamma interaction
      with the 2-NH2 group of guanine in the C site. Steric considerations favor
      binding of the nucleoside diphosphate to the A site. Site-directed replacements
      of key residues increased the nucleotide concentrations needed for 50% inhibition
      and in some cases perturbed synergism. Mutations in either of the nucleotide
      sites perturbed function at both sites, supporting the important role of
      synergism.

PMID- 9271503
TI  - Spectroscopic and enzymatic characterization of the active site dinuclear metal
      center of calcineurin: implications for a mechanistic role.
AB  - The active site of bovine brain calcineurin contains an Fe3+-Zn2+ dinuclear metal
      center. Replacement of Zn2+ with Fe2+ yields a mixed valence Fe3+-Fe2+ center
      that exhibits a characteristic EPR signal that can be used as a convenient
      spectroscopic probe of the active site. Addition of product phosphate to both the
      Fe3+-Fe2+ and Fe3+-Zn2+ forms of calcineurin led to perturbations of the
      respective EPR signals, indicating that phosphate affects the environment of the
      paramagnetic centers. Anaerobic titrations of the iron-substituted Fe3+-Fe2+
      enzyme with dithionite resulted in a gradual loss of activity toward pNPP that
      paralleled the loss of intensity of the EPR signal of the mixed valence diiron
      center. During dithionite reduction, an EPR resonance with g approximately 12
      appeared. The intensity of this resonance increased when the spectrum was
      recorded in a parallel mode cavity and was therefore attributed to a paramagnetic
      center with integer spin. Oxidation of the Fe3+-Fe2+ cluster to the diferric
      state by hydrogen peroxide also led to a loss of activity. These results indicate
      that the mixed valence oxidation state represents the catalytically competent
      form of the cluster. The dependence of the enzyme activity on the redox state of
      the cluster has implications for a mechanistic role.

PMID- 9271504
TI  - Identification of a glycosylated relaxin-like molecule from the male Atlantic
      stingray, Dasyatis sabina.
AB  - The alkaline gland fluid of the Atlantic stingray (Dasyatis sabina) contains a
      molecule that cross-reacts weakly to anti-porcine relaxin antibodies. This
      material was isolated and purified to homogeneity by reversed-phase high
      performance liquid chromatography. In SDS gel electrophoresis, the molecule
      showed an apparent molecular mass of 13 kDa which upon reduction formed two
      polypeptide chains of 4 and 9 kDa, respectively. Sequence analyses revealed a 27
      amino acid residue A chain and a 54-amino acid residue B chain which contained an
      N-glycosylation site in position B37. The distribution of the six cysteines and
      possibly the disulfide bonding is identical to that found in insulins and most
      relaxins. Although the stingray relaxin-like molecule contains the structurally
      relevant glycine residues within the A chain, in the midregion of the B chain it
      has only one of the two requisite binding site arginines, which explains the lack
      of relaxin bioactivity in standard mammalian assays. Stingray relaxin is the
      first member of the relaxin family identified in a nonhomeotherm male.
      Carbohydrate analysis of relaxin revealed an N-linked asialo, agalacto, bisected
      biantennary, and a core-fucosylated oligosaccharide in the position of Asn B37
      which makes it the first reported glycosylated relaxin-like molecule.

PMID- 9271505
TI  - Functional effects on the acetylcholine receptor of multiple mutations of gamma
      Asp174 and delta Asp180.
AB  - Residues gamma Asp174 and delta Asp180, previously implicated in the binding of
      acetylcholine (ACh) by the mouse muscle ACh receptor, were each mutated to nine
      other residues, Asn, Glu, Thr, Ala, Cys, His, Val, Tyr, and Lys. The effects of
      the mutations on ACh-induced current was determined on surface receptors
      containing wild-type alpha and beta subunits and mutant gamma and delta subunits.
      The mutations increased the concentration of ACh eliciting half-maximal current
      (EC50) by factors from 22 for the Glu mutant to 660 for the Lys mutant. Analysis
      of the effects in terms of the difference in the accessible surface areas of the
      mutant and wild-type side chains and the difference in side-chain charges
      indicated that, per binding site, Delta DeltaG0 for activation was a sum of 10
      cal mol-1 A-2 of change in side-chain accessible surface area and of 0.95 kcal
      mol-1 positive step-1 in side-chain charge, equivalent to 1 mol of charge falling
      through 42 mV. The effects on the concentration of ACh (IC50, ACh) and of d
      tubocurarine (IC50,dTC) causing half-maximal retardation of alpha-bungarotoxin
      binding were determined on complexes containing wild-type alpha and beta subunits
      and either mutant gamma or mutant delta subunit. The effects on IC50,ACh
      correlated well with the effects on EC50, with a similar magnitude for the
      influence of side-chain charge on the free energy of binding (in this case to the
      desensitized state) and on the electrostatic potential at the binding site. The
      effects on IC50,dTC were in all cases less than the effects on IC50,ACh, and the
      two sets of effects were poorly correlated. In line with the higher ACh affinity
      and lower d-tubocurarine affinity of the alpha-delta binding site compared to the
      alpha-gamma binding site, mutations of delta Asp180 had a greater effect on
      IC50,ACh than did the same mutations of gamma Asp174, and vice versa for effects
      on IC50,dTC. Consequently, all mutations decreased the asymmetry in the binding
      properties of the two types of sites.

PMID- 9271506
TI  - Sphingosine 1-phosphate regulates melanoma cell motility through a receptor
      coupled extracellular action and in a pertussis toxin-insensitive manner.
AB  - Our previous work showed that sphingosine 1-phosphate (Sph-1-P) inhibits the cell
      motility of mouse melanoma B16/F10, and other types of cells at 10-100 nM
      concentrations. In the present paper, we have identified and characterized
      specific cell surface binding sites for Sph-1-P in F10 cells. Sph-1-P immobilized
      on controlled pore glass beads inhibited the motility of F10 cells, suggesting
      that Sph-1-P acts on the cells from the outside. Binding assays with [3H]Sph-1-P
      revealed the presence of specific cell surface binding sites for Sph-1-P in F10
      cells. Scatchard analysis demonstrated a single class of binding sites for Sph-1
      P. The binding of [3H]Sph-1-P to F10 cells was inhibited by the addition of
      excess unlabeled Sph-1-P but not other natural sphingolipids. The specific
      binding was also sensitive to treatment with a protease. Using Sph-1-P
      immobilized affinity chromatography, we, for the first time, identified 41-kDa
      and 79-kDa Sph-1-P binding proteins on the melanoma cell surface, although the 41
      kDa protein was less specific to Sph-1-P. We demonstrated that pertussis toxin
      (PTX) treatment did not abolish the motility inhibition by Sph-1-P, suggesting
      that no PTX-sensitive G-protein is involved in the signaling. Furthermore, Sph-1
      P was found to be specifically released from mouse BALB/3T3 clone A31 cells and
      F10 cells. Collectively, these results strongly suggest that Sph-1-P regulates
      melanoma cell motility through an extracellular action by specific binding to
      cell surface receptor protein(s), which is independent of PTX-sensitive G
      protein.

PMID- 9271507
TI  - The physical exchange of factor VIII (FVIII) between von Willebrand factor and
      activated platelets and the effect of the FVIII B-domain on platelet binding.
AB  - Normal hemostasis proceeds through the assembly of coagulant complexes on a lipid
      surface derived from activated platelets. The activation complex assembly is
      governed by multiple factors including the binding constants (Kd) of the
      coagulant factors for the lipid surface. The formation of the tenase complex
      requires delivery of factor VIII (FVIII) to the activated lipid surface by von
      Willebrand factor (vWF). Using electrophoretic quasi-elastic light scattering
      (ELS), we have examined the interaction of FVIII in the presence and absence of
      vWF with both resting and activated gel-filtered human platelets. Resting
      platelets do not bind FVIII. Platelets activated by thrombin, epinephrine, or
      SFLLRN, but not ADP or collagen, bind unactivated FVIII if vWF is not present. In
      the absence of vWF, unactivated FVIII binds to activated platelets with a Kd of
      10.4 nM. B-domain deleted FVIII binds to activated platelets with a Kd of 5.1 nM.
      Thrombin -activated FVIII (FVIIIa) binds to activated platelets with a Kd of 1.7
      nM. The activation of FVIII while bound to the platelet surface can be monitored
      as a function of time. In the presence of vWF, binding of unactivated FVIII to
      activated platelets was inhibited, but not the binding of FVIIIa. Displacement of
      bound unactivated FVIII from the platelet surface occurs when vWF is added to the
      FVIII-platelet complex. The binding of FVIII to activated platelets is affected
      by the B-domain, the state of FVIII activation, and the presence of soluble vWF
      and proceeds as a multistep process. FVIII binding by activated platelets is not
      affected by platelet gpIIb/IIIa or by platelet vWF.

PMID- 9271508
TI  - Partial activation of the factor VIIIa-factor IXa enzyme complex by dihexanoic
      phosphatidylserine at submicellar concentrations.
AB  - Phosphatidylserine (PS)-containing membranes increase the kcat of the factor
      VIIIa-factor IXa enzyme complex by more than 1000-fold. While PS supports
      specific, high-affinity membrane binding of factor VIIIa and factor IXa, it is
      not known whether PS is the lipid that activates the membrane-bound complex. It
      is also not known whether PS or other activating lipids must reside in the two
      dimensional membrane matrix for efficacy. We have found that submicellar
      concentrations of dihexanoic phosphatidylserine (C6PS) increase the activity of
      the factor VIIIa-factor IXa complex in a biphasic manner with half-maximal
      concentrations of 0.2 and 1.6 mM while the micelle-forming concentration is 4.0
      mM. Increased cleavage of factor X at 0.25 mM C6PS was due to a 25-fold
      enhancement of the kcat and a 30-fold increase in the affinity of factor VIIIa
      for factor IXa. C6 phosphatidylethanolamine and C6 phosphatidic acid, but not C6
      phosphatidylcholine, also accelerated the Xase complex, indicating that kcat
      enhancement has less structural specificity than membrane binding. Submicellar
      C6PS enhanced activity of factor IXa in the absence of factor VIIIa, but the
      effect was due to a decreased KM rather than an increased kcat. These results
      suggest that activation of the factor VIIIa-factor IXa complex can result from
      binding of individual C6PS molecules or small aggregates in the absence of a
      membrane bilayer. They provide a model system in which the phospholipid-induced
      activation may be distinguished from membrane-binding of the enzyme complex.

PMID- 9271509
TI  - The dihydropyridine dexniguldipine hydrochloride inhibits cleavage and religation
      reactions of eukaryotic DNA topoisomerase I.
AB  - Dexniguldipine hydrochloride (B859-35, a dihydropyridine with antitumor and
      multidrug resistance-reverting activity) inhibits both the DNA cleavage and
      religation reactions of purified human DNA topoisomerase I at concentrations >1
      microM, whereas at concentrations <1 microM it inhibits selectively the
      religation step and stabilizes the covalent topoisomerase I-DNA intermediate in a
      similar fashion as camptothecin. Inhibition of religation by camptothecin can be
      overcome by increasing the concentration of the DNA substrate in the religation
      reaction, indicating a competitive type of inhibition. In contrast,
      dexniguldipine hydrochloride decreases rate constants of topoisomerase I-mediated
      DNA religation independently of the concentration of the DNA substrate,
      suggesting a noncompetitive mechanism of inhibition, which is different from that
      of camptothecin.

PMID- 9271510
TI  - Reconstitution and further characterization of the cholesterol transport activity
      of the small-intestinal brush border membrane.
AB  - The sterol (free and esterified cholesterol) transport activity of the small
      intestinal brush border membrane was solubilized with the short-chain detergent
      diheptanoylphosphatidylcholine and reconstituted to an artificial membrane system
      (proteoliposomes). The resulting proteoliposomes were identified as unilamellar
      membrane vesicles ranging in size between 50 and 200 nm with a broad maximum at
      70-110 nm. That the sterol transport protein was indeed incorporated into the
      lipid bilayer was shown by density gradient centrifugation on a Ficoll gradient:
      the proteoliposomes yielded a single band with an apparent density of 1.035 g/mL.
      By subjecting solubilized brush border membrane vesicles (BBMV) to gel filtration
      on Sephadex G-200 prior to reconstitution, a 7-fold enrichment of the sterol
      transport activity was achieved relative to the original BBMV. The experimental
      evidence presented lends strong support to the notion that the sterol transport
      protein is an integral protein of the brush border membrane which is anchored in
      the lipid bilayer by at least one hydrophobic domain. The active center(s) is
      (are) exposed to the external side of the membrane. Anchoring of this protein to
      the lipid bilayer by a glycosylphosphatidylinositol moiety is unlikely. The
      reconstituted proteoliposomes behaved very similarly to the original BBMV in
      terms of facilitated sterol uptake. Using these proteoliposomes, a hitherto
      unknown activity of the brush border membrane was discovered. Long-chain
      triacylglycerols can be taken up by this membrane as such and need not be
      hydrolyzed prior to absorption.

PMID- 9271562
TI  - Molecular manipulation of microstructures: biomaterials, ceramics, and
      semiconductors.
AB  - Organic molecules can alter inorganic microstructures, offering a very powerful
      tool for the design of novel materials. In biological systems, this tool is often
      used to create microstructures in which the organic manipulators are a minority
      component. Three groups of materials-biomaterials, ceramics, and semiconductors
      have been selected to illustrate this concept as used by nature and by synthetic
      laboratories exploring its potential in materials technology. In some of nature's
      biomaterials, macromolecules such as proteins, glycoproteins, and polysaccharides
      are used to control nucleation and growth of mineral phases and thus manipulate
      microstructure and physical properties. This concept has been used synthetically
      to generate apatite-based materials that can function as artificial bone in
      humans. Synthetic polymers and surfactants can also drastically change the
      morphology of ceramic particles, impart new functional properties, and provide
      new processing methods for the formation of useful objects. Interesting
      opportunities also exist in creating semiconducting materials in which molecular
      manipulators connect quantum dots or template cavities, which change their
      electronic properties and functionality.

PMID- 9271511
TI  - Kinetic evidence for peptide-induced oligomerization of the molecular chaperone
      DnaK at heat shock temperatures.
AB  - The pre-steady-state kinetics of the binding of a fluorescent peptide (dansyl
      KLIGVLSSLFRPK, fVSV13) to the Escherichia coli molecular chaperone DnaK were
      investigated over a range of temperatures (25-42 degrees C). At 42 degrees C,
      over a wide range of peptide concentrations, the fVSV13 peptide bound to DnaK
      with biphasic kinetics: a rapid burst in the DnaK-fVSV13 signal in the first 5 s
      was followed by a gradual reduction in the signal over the next 100 s. The
      descending portion of each biphasic trace followed the equation F(t) = DeltaF
      exp(-kdt) + Finfinity, where DeltaF, kd, and Finfinity are the amplitude, the
      apparent first-order rate constant, and the fluorescence end point, respectively.
      Both DeltaF and kd increased with increasing concentrations of DnaK, which
      suggests that the loss of the DnaK-fVSV13 signal is caused by a bimolecular
      reaction. We propose that (i) the fVSV13 peptide binds to and induces a
      conformational change in the DnaK monomer [E + P right harpoon over left harpoon
      (EP)*]; and (ii) the conformational change promotes the formation of oligomeric
      DnaK-peptide complexes [En + (EP)* right harpoon over left harpoon En-EP]. The
      term (EP)* denotes a monomeric DnaK-peptide complex in which the bound peptide is
      fluorescent; En-EP denotes an oligomeric DnaK-peptide complex in which the
      fluorescence of the bound peptide is quenched. Numerical fitting of the stopped
      flow data to reactions (i) and (ii) yielded values for the four rate constants.
      When the proposed kinetic model was tested by conducting experiments in the
      presence of excess peptide or excess ATP&sbd;conditions which inhibit
      oligomerization&sbd;DnaK-fVSV13 complex formation proceeded to stable asymptotes,
      with no reduction in the DnaK-fVSV13 signal at long times.

PMID- 9271564
TI  - A conformational switch in Escherichia coli 16S ribosomal RNA during decoding of
      messenger RNA.
AB  - Direct evidence is presented for a conformational switch in 16S ribosomal RNA
      (rRNA) that affects tRNA binding to the ribosome and decoding of messenger RNA
      (mRNA). These data support the hypothesis that dynamic changes in rRNA structure
      occur during translation. The switch involves two alternating base-paired
      arrangements apparently facilitated by ribosomal proteins S5 and S12, and
      produces significant changes in the rRNA structure. Chemical probing shows
      reciprocal enhancements or protections at sites in 16S rRNA that are at or very
      near sites that were previously crosslinked to mRNA. These data indicate that the
      switch affects codon-anticodon arrangement and proper selection of tRNA at the
      ribosomal A site, and that the switch is a fundamental mechanism in all
      ribosomes.

PMID- 9271576
TI  - A critical role for tapasin in the assembly and function of multimeric MHC class
      I-TAP complexes.
AB  - Newly assembled major histocompatibility complex (MHC) class I molecules,
      together with the endoplasmic reticulum chaperone calreticulin, interact with the
      transporter associated with antigen processing (TAP) through a molecule called
      tapasin. The molecular cloning of tapasin revealed it to be a transmembrane
      glycoprotein encoded by an MHC-linked gene. It is a member of the immunoglobulin
      superfamily with a probable cytoplasmic endoplasmic reticulum retention signal.
      Up to four MHC class I-tapasin complexes were found to bind to each TAP molecule.
      Expression of tapasin in a negative mutant human cell line (220) restored class I
      TAP association and normal class I cell surface expression. Tapasin expression
      also corrected the defective recognition of virus-infected 220 cells by class I
      restricted cytotoxic T cells, establishing a critical functional role for tapasin
      in MHC class I-restricted antigen processing.

PMID- 9271577
TI  - Induced alpha helix in the VP16 activation domain upon binding to a human TAF.
AB  - Activation domains are functional modules that enable sequence-specific DNA
      binding proteins to stimulate transcription. The structural basis for the
      function of activation domains is poorly understood. A combination of nuclear
      magnetic resonance (NMR) and biochemical experiments revealed that the minimal
      acidic activation domain of the herpes simplex virus VP16 protein undergoes an
      induced transition from random coil to alpha helix upon binding to its target
      protein, hTAFII31 (a human TFIID TATA box-binding protein-associated factor).
      Identification of the two hydrophobic residues that make nonpolar contacts
      suggests a general recognition motif of acidic activation domains for hTAFII31.

PMID- 9271578
TI  - Accelerated aging and nucleolar fragmentation in yeast sgs1 mutants.
AB  - The SGS1 gene of yeast encodes a DNA helicase with homology to the human WRN
      gene. Mutations in WRN result in Werner's syndrome, a disease with symptoms
      resembling premature aging. Mutation of SGS1 is shown to cause premature aging in
      yeast mother cells on the basis of a shortened life-span and the aging-induced
      phenotypes of sterility and redistribution of the Sir3 silencing protein from
      telomeres to the nucleolus. Further, in old sgs1 cells the nucleolus is enlarged
      and fragmented-changes that also occur in old wild-type cells. These findings
      suggest a conserved mechanism of cellular aging that may be related to nucleolar
      structure.

PMID- 9271579
TI  - Outer periarteriolar lymphoid sheath arrest and subsequent differentiation of
      both naive and tolerant immunoglobulin transgenic B cells is determined by B cell
      receptor occupancy.
AB  - T-dependent B cell responses in the spleen are initiated in the outer
      periarteriolar lymphoid sheath (PALS) and culminate in the generation of
      proliferative foci and germinal center reactions. By pulsing anti-hen egg
      lysozyme (HEL) immunoglobulin transgenic (IgTg) B cells with various
      concentrations of HEL in vitro before adoptive transfer into normal recipients,
      it was shown that a critical number of B cell receptors (BCRs) must be ligated
      for B cells to undergo arrest in the outer PALS. T cell help was manipulated
      independently of the BCR stimulus by incubating B cells expressing the
      appropriate major histocompatibility complex class II antigen with a peptide
      recognized by CD4(+) TCR Tg T cells. B cells which either failed to arrest in the
      outer PALS due to a subthreshold BCR stimulus, or arrested only transiently due
      to the brevity of the BCR stimulus, underwent an abortive response within the
      follicles when provided with T cell help. In contrast, naive B cells stimulated
      by a sustained, suprathreshold concentration of either foreign or self-antigen
      and given T cell help, proliferated in the outer PALS and then differentiated.
      Outer PALS arrest was not influenced by the nature of the B cells occupying the
      follicle, but appeared to be determined solely by the magnitude of BCR
      stimulation. Thus antigen-pulsed B cells arrested in the outer PALS in an
      identical manner irrespective of whether the follicles comprised a population of
      normal B cells with multiple specificities, a monoclonal naive population, or a
      monoclonal population of tolerant B cells. In addition, tolerant B cells were
      found to relocate from the follicles to the outer PALS of HEL/anti-HEL double Tg
      mice in which the concentration of soluble self-antigen had been increased by
      zinc feeding. Similarly, when anti-HEL Tg mice were crossed with a second HEL Tg
      strain expressing a higher concentration of soluble HEL, the tolerant anti-HEL Tg
      B cells were located constitutively in the outer PALS. Thus, subtle variations in
      antigen concentration resulted in dramatic changes in positioning of B cells
      within the spleen. A series of mixed bone marrow chimeras in which the effective
      antigen concentration was inversely related to the number of self-reactive B
      cells due to absorption of antigen by transgene-encoded membrane and secreted Ig,
      was used to confirm that alteration in B cell position previously attributed to
      changes in follicular composition could be explained on the basis of available
      antigen concentration, rather than the diversity of the repertoire.

PMID- 9271580
TI  - Self antigens expressed by solid tumors Do not efficiently stimulate naive or
      activated T cells: implications for immunotherapy.
AB  - Induction and maintenance of cytotoxic T lymphocyte (CTL) activity specific for a
      primary endogenous tumor was investigated in vivo. The simian virus 40 T antigen
      (Tag) expressed under the control of the rat insulin promoter (RIP) induced
      pancreatic beta-cell tumors producing insulin, causing progressive hypoglycemia.
      As an endogenous tumor antigen, the lymphocytic choriomeningitis virus (LCMV)
      glycoprotein (GP) was introduced also under the control of the RIP. No
      significant spontaneous CTL activation against GP was observed. However, LCMV
      infection induced an antitumor CTL response which efficiently reduced the tumor
      mass, resulting in temporarily normalized blood glucose levels and prolonged
      survival of double transgenic RIP(GP x Tag2) mice (137 +/- 18 d) as opposed to
      control RIP-Tag2 mice (88 +/- 8 d). Surprisingly, the tumor-specific CTL response
      was not sustained despite the facts that the tumor cells continued to express MHC
      class I and LCMV-GP-specific CTLs were present and not tolerized. Subsequent
      adoptive transfer of virus activated spleen cells into RIP(GP x Tag2) mice
      further prolonged survival (168 +/- 11 d), demonstrating continued expression of
      the LCMV-GP tumor antigen and MHC class I. The data show that the tumor did not
      spontaneously induce or maintain an activated CTL response, revealing a profound
      lack of immunogenicity in vivo. Therefore, repetitive immunizations are necessary
      for prolonged antitumor immunotherapy. In addition, the data suggest that the
      risk for induction of chronic autoimmune diseases is limited, which may encourage
      immunotherapy against antigens selectively but not exclusively expressed by the
      tumor.

PMID- 9271581
TI  - Polymerase chain reaction selects a novel disintegrin proteinase from CD40
      activated germinal center dendritic cells.
AB  - To identify genes expressed by a specific subset of dendritic cells found in vivo
      a polymerase chain reaction-based cDNA subtraction technique was applied to the
      recently described germinal center dendritic cells. A novel member of the
      disintegrin metalloproteinase family was cloned which comprises a not typical
      zinc-chelating catalytic site most similar to a bacterial metalloproteinase.
      Dendritic cell precursors or immature dendritic cells express no or low levels of
      the message. It is induced to high levels upon spontaneous or CD40-dependent
      maturation and in a mixed lymphocyte reaction. In situ hybridization showed
      distinct expression of this gene in the germinal center. This, together with the
      findings that certain disintegrin metalloproteinases regulate the activity of
      tumor necrosis factor alpha and that metalloproteinases have also been implicated
      in FasL processing, suggest that this novel molecule may play an important role
      in dendritic cell function and their interactions with germinal center T cells.

PMID- 9271583
TI  - Antigen-unspecific B cells and lymphoid dendritic cells both show extensive
      surface expression of processed antigen-major histocompatibility complex class II
      complexes after soluble protein exposure in vivo or in vitro.
AB  - Intravenous (i.v.) injection of high amounts of soluble proteins often results in
      the induction of antigen-specific tolerance or deviation to helper rather than
      inflammatory T cell immunity. It has been proposed that this outcome may be due
      to antigen presentation to T cells by a large cohort of poorly costimulatory or
      IL-12-deficient resting B cells lacking specific immunoglobulin receptors for the
      protein. However, previous studies using T cell activation in vitro to assess
      antigen display have failed to support this idea, showing evidence of specific
      peptide-major histocompatibility complex (MHC) class II ligand only on purified
      dendritic cells (DC) or antigen-specific B cells isolated from protein injected
      mice. Here we reexamine this question using a recently derived monoclonal
      antibody specific for the T cell receptor (TCR) ligand formed by the association
      of the 46-61 determinant of hen egg lysozyme (HEL) and the mouse MHC class II
      molecule I-Ak. In striking contrast to conclusions drawn from indirect T cell
      activation studies, this direct method of TCR ligand analysis shows that i.v.
      administration of HEL protein results in nearly all B cells in lymphoid tissues
      having substantial levels of HEL 46-61-Ak complexes on their surface. DC readily
      isolated from spleen also display this TCR ligand on their surface. Although the
      absolute number of displayed ligands is greater on such DC, the relative specific
      ligand expression compared to total MHC class II levels is similar or greater on
      B cells. These results demonstrate that in the absence of activating stimuli,
      both lymphoid DC and antigen-unspecific B cells present to a similar extent class
      II-associated peptides derived from soluble proteins in extracellular fluid. The
      numerical advantage of the TCR ligand-bearing B cells may permit them to interact
      first or more often with naive antigen-specific T cells, contributing to the
      induction of high-dose T cell tolerance or immune deviation.

PMID- 9271582
TI  - High levels of a major histocompatibility complex II-self peptide complex on
      dendritic cells from the T cell areas of lymph nodes.
AB  - T lymphocytes recirculate continually through the T cell areas of peripheral
      lymph nodes. During each passage, the T cells survey the surface of large
      dendritic cells (DCs), also known as interdigitating cells. However, these DCs
      have been difficult to release from the lymph node. By emphasizing the use of
      calcium-free media, as shown by Vremec et al. (Vremec, D., M. Zorbas, R. Scollay,
      D.J. Saunders, C.F. Ardavin, L. Wu, and K. Shortman. 1992. J. Exp. Med. 176:47
      58.), we have been able to release and enrich DCs from the T cell areas. The DCs
      express the CD11c leukocyte integrin, the DEC-205 multilectin receptor for
      antigen presentation, the intracellular granule antigens which are recognized by
      monoclonal antibodies M342, 2A1, and MIDC-8, very high levels of MHC I and MHC
      II, and abundant accessory molecules such as CD40, CD54, and CD86. When examined
      with the Y-Ae monoclonal which recognizes complexes formed between I-Ab and a
      peptide derived from I-Ealpha, the T cell area DCs expressed the highest levels.
      The enriched DCs also stimulated a T-T hybridoma specific for this MHC II-peptide
      complex, and the hybridoma underwent apoptosis. Therefore DCs within the T cell
      areas can be isolated. Because they present very high levels of self peptides,
      these DCs should be considered in the regulation of self reactivity in the
      periphery.

PMID- 9271584
TI  - Impaired bone marrow microenvironment and immune function in T cell protein
      tyrosine phosphatase-deficient mice.
AB  - The T cell protein tyrosine phosphatase (TC-PTP) is one of the most abundant
      mammalian tyrosine phosphatases in hematopoietic cells; however, its role in
      hematopoietic cell function remains unknown. In this report, we investigated the
      physiological function(s) of TC-PTP by generating TC-PTP-deficient mutant mice.
      The three genotypes (+/+, +/-, -/-) showed mendelian segregation at birth (1:2:1)
      demonstrating that the absence of TC-PTP was not lethal in utero, but all
      homozygous mutant mice died by 3-5 wk of age, displaying runting, splenomegaly,
      and lymphadenopathy. Homozygous mice exhibited specific defects in bone marrow
      (BM), B cell lymphopoiesis, and erythropoiesis, as well as impaired T and B cell
      functions. However, myeloid and macrophage development in the BM and T cell
      development in the thymus were not significantly affected. BM transplantation
      experiments showed that hematopoietic failure in TC-PTP -/- animals was not due
      to a stem cell defect, but rather to a stromal cell deficiency. This study
      demonstrates that TC-PTP plays a significant role in both hematopoiesis and
      immune function.

PMID- 9271585
TI  - Tumor eradication by wild-type p53-specific cytotoxic T lymphocytes.
AB  - The tumor suppressor protein p53 is overexpressed in close to 50% of all human
      malignancies. The p53 protein is therefore an attractive target for
      immunotherapy. Cytotoxic T lymphocytes (CTLs) recognizing a murine wild-type p53
      peptide, presented by the major histocompatibility complex class I molecule H
      2Kb, were generated by immunizing p53 gene deficient (p53 -/-) C57BL/6 mice with
      syngeneic p53-overexpressing tumor cells. Adoptive transfer of these CTLs into
      tumor-bearing p53 +/+ nude mice caused complete and permanent tumor eradication.
      Importantly, this occurred in the absence of any demonstrable damage to normal
      tissue. When transferred into p53 +/+ immunocompetent C57BL/6 mice, the CTLs
      persisted for weeks in the absence of immunopathology and were capable of
      preventing tumor outgrowth. Wild-type p53-specific CTLs can apparently
      discriminate between p53-overexpressing tumor cells and normal tissue, indicating
      that widely expressed autologous molecules such as p53 can serve as a target for
      CTL-mediated immunotherapy of tumors.

PMID- 9271586
TI  - Altered proliferative response by T lymphocytes of Ly-6A (Sca-1) null mice.
AB  - Ly-6A is a murine antigen which is implicated in lymphocyte activation and may be
      involved in activation of hematopoietic stem cells. Antibody cross-linking
      studies and antisense experiments have suggested that Ly-6A is a lymphocyte
      coactivation molecule. To better understand the function of Ly-6A, we used gene
      targeting to produce Ly-6A null mice which are healthy and have normal numbers
      and percentages of hematopoietic lineages. However, T lymphocytes from Ly-6A
      deficient animals proliferate at a significantly higher rate in response to
      antigens and mitogens than wild-type littermates. In addition, Ly-6A mutant
      splenocytes generate more cytotoxic T lymphocytes compared to wild-type
      splenocytes when cocultured with alloantigen. This enhanced proliferation is not
      due to alterations in kinetics of response, sensitivity to stimulant
      concentration, or cytokine production by the T cell population, and is manifest
      in both in vivo and in vitro T cell responses. Moreover, T cells from Ly-6A
      deficient animals exhibit a prolonged proliferative response to antigen
      stimulation, thereby suggesting that Ly-6A acts to downmodulate lymphocyte
      responses.

PMID- 9271587
TI  - The lymphocyte function-associated antigen 1 I domain is a transient binding
      module for intercellular adhesion molecule (ICAM)-1 and ICAM-3 in hydrodynamic
      flow.
AB  - The I domain of lymphocyte function-associated antigen (LFA)-1 contains an
      intercellular adhesion molecule (ICAM)-1 and ICAM-3 binding site, but the
      relationship of this site to regulated adhesion is unknown. To study the adhesive
      properties of the LFA-1 I domain, we stably expressed a GPI-anchored form of this
      I domain (I-GPI) on the surface of baby hamster kidney cells. I-GPI cells bound
      soluble ICAM-1 (sICAM-1) with a low avidity and affinity. Flow cell experiments
      demonstrated a specific rolling interaction of I-GPI cells on bilayers containing
      purified full length ICAM-1 or ICAM-3. The LFA-1 activating antibody MEM-83, or
      its Fab fragment, decreased the rolling velocity of I-GPI cells on ICAM-1
      containing membranes. In contrast, the interaction of I-GPI cells with ICAM-3 was
      blocked by MEM-83. Rolling of I-GPI cells was dependent on the presence of Mg2+.
      Mn2+ only partially substituted for Mg2+, giving rise to a small fraction of
      rolling cells and increased rolling velocity. This suggests that the I domain
      acts as a transient, Mg2+-dependent binding module that cooperates with another
      Mn2+-stimulated site in LFA-1 to give rise to the stable interaction of intact
      LFA-1 with ICAM-1.

PMID- 9271588
TI  - Epstein-Barr virus binding to CD21 activates the initial viral promoter via NF
      kappaB induction.
AB  - Epstein-Barr virus (EBV), an oncogenic human herpesvirus, binds to and infects
      normal human B lymphocytes via CD21, the CR2 complement receptor. Studies of the
      mechanisms that enable EBV to infect nonactivated, noncycling B cells provide
      compelling evidence for a sequence of events in which EBV binding to CD21 on
      purified resting human B cells rapidly activates the NF-kappaB transcription
      factor, which, in turn, binds to and mediates transcriptional activation of Wp,
      the initial viral latent gene promoter. Thus, EBV binding to its cellular
      receptor on resting B cells triggers an NF-kappaB-dependent intracellular
      signaling pathway which is required for infection.

PMID- 9271589
TI  - Identification of human neutrophil-derived cathepsin G and azurocidin/CAP37 as
      chemoattractants for mononuclear cells and neutrophils.
AB  - Macrophage infiltration into inflammatory sites is generally preceded by
      neutrophils. This suggests neutrophils may be the source of chemotactic factors
      for monocytes. To identify these putative monocyte attractants, we have
      systematically prepared neutrophil granules, lysed them, and sequentially
      purified the released proteins by several reverse phase chromatography
      procedures. Assays for monocyte chemotactic activity of the chromatography
      fractions yielded a major peak of activity associated with a protein of 30 kD,
      according to SDS-PAGE analysis. NH2-terminal sequence of the protein revealed
      this to be identical to cathepsin G. The monocyte chemotactic activity of human
      cathepsin G was dose dependent with optimal concentration at 0.5-1 microg/ml.
      Cathepsin G is chemotactic rather than chemokinetic for monocytes, as
      demonstrated by checkerboard analysis. Cathepsin G-induced monocyte chemotaxis is
      partially pertussis toxin sensitive implying the involvement of a G protein
      coupled receptor. Enzymatic activity of cathepsin G is associated with its
      monocyte chemotactic activity, since DFP- or PMSF-inactivated cathepsin G no
      longer induced monocyte migration. The chemotactic activity of cathepsin G can
      also be completely blocked by alpha1 antichymotrypsin, a specific inhibitor of
      chymotrypsin-like proteinases present in human plasma. In addition, cathepsin G
      is also a potent chemoattractant for neutrophils and a chemokinetic stimulant for
      T cells. In the course of pursuing these in vitro studies, we established that
      the T cell chemoattractant, azurocidin/CAP37 from human neutrophil granules, at
      doses of 0.05 to 5 microg/ml, was chemotactic for monocytes and neutrophils. As
      predicted from the in vitro chemotactic activity, subcutaneous injection of
      cathepsin G into BALB/c mice led to infiltration of both mononuclear cells and
      neutrophils. Thus, the transition of inflammatory exudate from neutrophil to
      mononuclear cells can be mediated, at least in part, by extracellular release of
      neutrophil granule proteins such as cathepsin G and azurocidin/CAP37.

PMID- 9271590
TI  - Impaired inflammatory responses in the reverse arthus reaction through genetic
      deletion of the C5a receptor.
AB  - We recently demonstrated that gene-targeted disruption of the C5a anaphylatoxin
      receptor prevented lung injury in immune complex-mediated inflammation. In this
      study, we compare the effect of C5aR deficiency in immune complex-induced
      inflammation in the peritoneal cavity and skin with the results derived from our
      immune complex alveolitis model. C5aR- deficient mice exhibit decreased migration
      of neutrophils and decreased levels of TNF-alpha and interleukin 6 in the
      peritoneal reverse passive Arthus reaction compared to their wild-type
      littermates. In the reverse passive Arthus reaction in the skin the C5aR was also
      required for the full expression of neutrophil influx and edema formation; C5aR
      deficient mice showed reduced neutrophil migration and microvascular permeability
      changes. In contrast to our studies in immune complex-induced lung inflammation,
      C5aR deficiency does not completely prevent injury in the peritoneal cavity and
      skin. These data indicate a dominant role for the C5aR and its ligand in the
      reverse passive Arthus reaction in the lung and a synergistic role together with
      other inflammatory mediators in immune complex-mediated peritonitis and skin
      injury.

PMID- 9271591
TI  - Single cell analysis reveals regulated hierarchical T cell antigen receptor
      signaling thresholds and intraclonal heterogeneity for individual cytokine
      responses of CD4+ T cells.
AB  - T cell receptor (TCR) recognition of peptide-major histocompatibility complex
      antigens can elicit a diverse array of effector activities. Here we
      simultaneously analyze TCR engagement and the production of multiple cytokines by
      individual cells in a clonal Th1 CD4(+) cell population. Low concentrations of
      TCR ligand elicit only interferon-gamma (IFN-gamma) production. Increasing ligand
      recruits more cells into the IFN-gamma+ pool, increases IFN-gamma produced per
      cell, and also elicits IL-2, but only from cells already making IFN-gamma. Most
      cells producing only IFN-gamma show less TCR downmodulation than cells producing
      both cytokines, consistent with a requirement for more TCR signaling to elicit IL
      2 than to evoke IFN-gamma synthesis. These studies emphasize the hierarchical
      organization of TCR signaling thresholds for induction of distinct cytokine
      responses, and demonstrate that this threshold phenomenon applies to individual
      cells. The existence of such thresholds suggests that antigen dose may dictate
      not only the extent, but also the quality of an immune response, by altering the
      ratios of the cytokines produced by activated T cells. The quantitative
      relationships in this response hierarchy change in response to costimulation
      through CD28 or LFA-1, as well as the differentiation state of the lymphocyte,
      explaining how variations in these parameters in the face of a fixed antigen load
      can qualitatively influence immune outcomes. Finally, although the IFN-gamma/IL-2
      hierarchy is seen with most cells, among cells with the greatest TCR
      downmodulation, some produce only IFN-gamma and not IL-2, and the amount of IFN
      gamma exceeds that in double producers. Thus, these single cell analyses also
      provide clear evidence of nonquantitative intraclonal heterogeneity in cytokine
      production by long-term Th1 cells, indicating additional complexity of T cell
      function during immune responses.

PMID- 9271592
TI  - Allelic exclusion in pTalpha-deficient mice: no evidence for cell surface
      expression of two T cell receptor (TCR)-beta chains, but less efficient
      inhibition of endogeneous Vbeta--> (D)Jbeta rearrangements in the presence of a
      functional TCR-beta transgene.
AB  - Although individual T lymphocytes have the potential to generate two distinct T
      cell receptor (TCR)-beta chains, they usually express only one allele, a
      phenomenon termed allelic exclusion. Expression of a functional TCR-beta chain
      during early T cell development leads to the formation of a pre-T cell receptor
      (pre-TCR) complex and, at the same developmental stage, arrest of further TCR
      beta rearrangements, suggesting a role of the pre-TCR in mediating allelic
      exclusion. To investigate the potential link between pre-TCR formation and
      inhibition of further TCR-beta rearrangements, we have studied the efficiency of
      allelic exclusion in mice lacking the pre-TCR-alpha (pTalpha) chain, a core
      component of the pre-TCR. Staining of CD3+ thymocytes and lymph node cells with
      antibodies specific for Vbeta6 or Vbeta8 and a pool of antibodies specific for
      most other Vbeta elements, did not reveal any violation of allelic exclusion at
      the level of cell surface expression. This was also true for pTalpha-deficient
      mice expressing a functionally rearranged TCR-beta transgene. Interestingly,
      although the transgenic TCR-beta chain significantly influenced thymocyte
      development even in the absence of pTalpha, it was not able to inhibit fully
      endogeneous TCR-beta rearrangements either in total thymocytes or in sorted CD25+
      pre-T cells of pTalpha-/- mice, clearly indicating an involvement of the pre-TCR
      in allelic exclusion.

PMID- 9271593
TI  - Beta2-microglobulin-deficient mice are resistant to bullous pemphigoid.
AB  - Recent understanding of the mechanism of immunoglobulin G (IgG) catabolism has
      yielded new insight into antibody-mediated diseases. We proposed that beta2
      microglobulin (beta2m)-deficient mice have been protected from systemic lupus
      erythematosis (SLE)-like syndromes because they lack the beta2m-associated IgG
      protection receptor (FcRn) and therefore catabolize IgG, including pathogenic IgG
      autoantibodies, considerably more rapidly than normal mice. Such an hypothesis
      would predict that beta2m-deficient mice would also be resistant to experimental
      bullous pemphigoid, a disease with a pathogenesis thought to be much simpler than
      SLE, being the result of antibody directed toward a pathogenic epitope on the
      epidermal hemidesmosome that anchors basal keratinocytes to the basement
      membrane. To test this hypothesis, we administered pathogenic rabbit antibody
      directed toward the hemidesmosome to beta2m-deficient mice and to normal control
      mice, both intraperitoneally and intradermally, and assessed the mice clinically,
      histologically, and immunologically for manifestations of skin disease. We found
      that the beta2m-deficient mice were protected when the antibody was given
      intraperitoneally whereas intradermal administration resulted in blisters only
      slightly less severe than those seen in normal mice. These data would indicate
      that autoantibody-mediated inflammation might be prevented or controlled by
      appropriate modulation of FcRn function.

PMID- 9271594
TI  - A CASP-8 mutation recognized by cytolytic T lymphocytes on a human head and neck
      carcinoma.
AB  - Of the antigens recognized on human tumors by autologous cytolytic T lymphocytes,
      all those defined thus far have been identified on melanoma or renal cell
      carcinoma. We report here the identification of an antigen recognized by
      autologous cytolytic T lymphocytes on a human squamous cell carcinoma of the oral
      cavity. The antigen is encoded by a mutated form of the CASP-8 gene. This gene,
      also named FLICE or MACH, codes for protease caspase-8, which is required for
      induction of apoptosis through the Fas receptor and tumor necrosis factor
      receptor-1. The mutation, which was found in the tumor cells but not in the
      normal cells of the patient, modifies the stop codon and adds an Alu repeat to
      the coding region, thereby lengthening the protein by 88 amino acids. The ability
      of the altered protein to trigger apoptosis appears to be reduced relative to the
      normal caspase-8. The antigenic peptide is a nonamer presented by HLA-B*3503. The
      five last amino acids are encoded by the extension of the reading frame caused by
      the mutation. This, together with previous observations of CDK4 and beta-catenin
      mutations, suggests that a significant fraction of the point mutations generating
      a tumor antigen also play a role in the tumoral transformation or progression.

PMID- 9271617
TI  - Cardiac effects of a competitive road race in trained child runners.
AB  - BACKGROUND: Animal studies and investigations of adult endurance athletes
      indicate a transient depression of myocardial function after prolonged high
      intensity exercise. PURPOSE: To determine whether a similar decrease is observed
      in child distance runners after a 4-km competitive road race. METHODS:
      Anthropometric measures, resting M-mode echocardiograms, maximal cycle exercise
      tests with estimation of cardiac output, and electrocardiograms were performed
      before a 4-km road race in nine run-trained boys (mean age, 12.2 years). Weight
      and resting echocardiogram and electrocardiogram were assessed immediately after
      the race. The entire test battery was repeated 24 hours later. RESULTS: Small but
      significant decreases in mean body weight and left ventricular end-diastolic
      dimension were observed immediately after the race, but there were no changes in
      shortening fraction. These findings are consistent with the effects of
      dehydration. Measurements returned to prerace values by 24 hours of recovery.
      Peak work capacity, maximal stroke volume, and maximal cardiac output were
      similar on prerace and 24-hour-postrace testing. No electrocardiographic
      abnormalities were observed. CONCLUSIONS: No adverse cardiac effects were
      observed from a competitive 4-km road race in male child distance runners.

PMID- 9271616
TI  - Health care utilization and health status in high-risk children randomized to
      receive group or individual well child care.
AB  - OBJECTIVE: To determine if health care utilization and health status among high
      risk children is modified by the use of group well child care (GWCC) as compared
      with traditional one-to-one individual well child care (IWCC). STUDY DESIGN:
      Randomized controlled trial. PARTICIPANTS: Children less than 4 months old from
      families with at least one of the following maternal risk factors: poverty,
      single marital status, age <20 years at delivery, less than a high school
      education, previous substance abuse, or history of abuse as a child. SETTING: Two
      urban, university pediatric clinics in Seattle, Washington. INTERVENTIONS:
      Children were randomized to receive GWCC or IWCC at the time of enrollment.
      Health supervision visits with two study nurse practitioners were scheduled at 4,
      5, 6, 8, 10, 12, and 15 months of age. GWCC study visits consisted of a group
      discussion of age-appropriate child-rearing issues, along with a physical
      examination, health screening, and immunizations. Health care utilization among
      children receiving GWCC and those randomized to IWCC was assessed using the
      following measures: compliance with study visits, compliance with any age
      appropriate health supervision visit, emergency department utilization, and
      immunization rates (defined as the proportion of children in each group who had
      received all recommended vaccines by 1 year of age). Provider time for GWCC and
      IWCC study visits was also recorded. Health status was measured using Stein's
      Functional Status IIR, completed by the mothers of study patients when their
      children completed the study at 15 months of age. RESULTS: A total of 106
      children received GWCC, whereas 104 were randomized to IWCC. Compliance with
      scheduled study visits was 47% for GWCC patients and 54% for IWCC recipients;
      overall compliance with any age-appropriate health supervision visit was 68% and
      66%, respectively. Provider time was similar for GWCC and IWCC visits. By the age
      of 1 year, 67% of GWCC recipients and 73% of those receiving IWCC had received
      three DTP/DT, three OPV/IPV, three Hib, and three hepatitis B immunizations. A
      total of 242 emergency department visits were made by study patients during their
      enrollment in the project; there was no difference in the average number of
      visits between GWCC or IWCC children. However, children receiving IWCC were more
      likely to have at least one emergency department visit than GWCC recipients. At
      the conclusion of the project, health status, as measured by the Functional
      Status IIR, was similar in GWCC and IWCC patients (mean scores 92.4 +/- 1.4 and
      92.5 +/- 1.1, respectively). CONCLUSIONS: Health care utilization and health
      status was similar in high-risk children whether they received GWCC or IWCC. GWCC
      is a viable format for health supervision visits in this population.

PMID- 9271618
TI  - Recognition of the presence and severity of newborn jaundice by parents, nurses,
      physicians, and icterometer.
AB  - OBJECTIVE: To determine how well parents, nurses, physicians, and an Ingram
      icterometer can detect the presence and the severity of jaundice in newborns.
      SETTING: Normal newborn nursery in a 340-bed teaching hospital. PATIENTS OR OTHER
      PARTICIPANTS: Nurses and physicians caring for nursery infants and parents of the
      infants. INTERVENTIONS: Physicians and nurses examining newborns documented
      whether they detected jaundice in the infants and, if so, the estimated bilirubin
      level and the extent of cephalocaudal progression of the jaundice. An assistant
      taught the parents how to examine the infants for jaundice and determine its
      cephalocaudal progression. The assistant also obtained icterometer readings.
      Bilirubin testing was performed according to usual clinical practice. OUTCOME
      MEASURES: Nurse and physician estimates of bilirubin levels; parent, nurse, and
      physician assessment of the presence of jaundice and its cephalocaudal
      progression; icterometer readings; bilirubin levels. RESULTS: There was moderate
      agreement about the presence of jaundice in the infants (pairwise kappa, 0.48)
      However, all infants with bilirubin levels >12 mg/dL were correctly identified as
      jaundiced by all examiners. The parents' assessment of cephalocaudal progression
      and the icterometer readings were most highly correlated with serum bilirubin
      levels (adjusted Pearson correlations, 0.71 and 0.57, respectively). CONCLUSIONS:
      Many parents can be taught to accurately assess cephalocaudal progression of
      jaundice in the hospital. The icterometer is a useful tool for assessing jaundice
      severity. Both parent assessment and the icterometer were more highly correlated
      with bilirubin levels than physician and nurse estimates in this study.
      Additional research is needed to determine how accurate these methods of clinical
      assessment are at the higher bilirubin levels that typically occur after hospital
      discharge.

PMID- 9271619
TI  - Impact of adopting lower-fat food choices on nutrient intake of American
      children.
AB  - OBJECTIVE: To compare the overall nutrient intake of American children (ages 2 to
      19) who exclusively use skim milk instead of 1%, 2%, or whole milk; lean meats
      instead of higher-fat meats; or fat-modified products instead of full-fat
      products. STUDY DESIGN: A unique sorting procedure was used to categorize
      respondents to the 1989-1991 Continuing Survey of Food Intake by Individuals
      according to reported use or nonuse of certain fat-reduction strategies.
      Differences in intake of 23 macronutrients and micronutrients, as well as energy,
      by exclusive users, mixed users, and nonusers of each strategy were statistically
      analyzed using analysis of variance with Scheffe's test. The number of fat
      reduction strategies used by the children as well as demographic characteristics
      also were analyzed. RESULTS: Only a small number of children qualified as
      exclusive users of skim milk (3%), lean meats (2%), and fat-modified products
      (1%). Energy intakes for all children were below 100% of the recommended dietary
      allowance. However, children (n = 85) who used skim milk exclusively in place of
      higher-fat milks closely approximated the current dietary recommendations (30%
      energy from fat, less than 10% from saturated fat, and less than 300 mg
      cholesterol) while maintaining adequate micronutrient intake and without
      significantly impacting energy. Children (n = 52) who used lean meats in place of
      higher-fat meats achieved the guideline for total fat; however, energy intake was
      70% of the recommended dietary allowance and vitamin E was 63%. Children (n = 20)
      who use only fat-modified versions of cheese, salad dressing, cake, pudding, and
      yogurt made no significant impact on their energy, fat, or micronutrient intake.
      Of the 3299 children in the data set, only 3 qualified as users of two fat
      reduction strategies and none qualified as users of all three strategies.
      Exclusive users of skim milk, lean meat, or fat-modified products were more
      likely to be female, white, and live in families with higher incomes. Those using
      skim milk or lean meat exclusively also were more likely to be older, whereas
      those exclusively using fat-modified products were younger. Furthermore, those
      using skim milk or fat-modified products exclusively were more likely to live in
      households where the head had more years of education, whereas those exclusively
      using lean meats were from households headed by those with slightly less years of
      education. CONCLUSIONS: Despite the inherent limitations of population-based food
      surveys (including issues of underreporting, lack of biological markers and
      accurate anthropometric measures, and limited nutrient databases), these results
      provide insight into the rate of use of certain lower-fat food choices by
      children and suggest exclusive use can facilitate achievement of contemporary
      dietary recommendations. The impact of using these fat-reduction strategies on
      children's overall nutrient intake differs depending on the strategy used. Use of
      skim milk is an economical single-food strategy that facilitates achievement of
      contemporary dietary guidelines while maintaining nutrient adequacy. Professional
      guidance is recommended for children who exclusively use lean meats to assure
      adequate intake of energy and vitamin E. The impact of fat-modified products
      needs to be monitored closely as the number of such products increases in the
      marketplace. Results of this study can be used by health professionals working
      with children and their parents to highlight the overall efficacy of dietary
      recommendations while alerting them to potential pitfalls.

PMID- 9271620
TI  - A missense cystic fibrosis transmembrane conductance regulator mutation with
      variable phenotype.
AB  - OBJECTIVE: Cystic fibrosis (CF) has variable clinical presentation. Disease
      severity is partially associated with the type of mutation. The aim of this study
      was to report genotype-phenotype analysis of the G85E mutation. PATIENTS: The
      phenotype of 12 patients (8 were from the same extended family, and 5 of them
      were siblings from 2 families) carrying at least one copy of the G85E mutation
      was evaluated and compared with the phenotype of 40 patients carrying the two
      severe mutations, W1282X and/or DeltaF508 (group 1), and with 20 patients
      carrying the splicing mutation, 3849+10kb C->T, which was found to be associated
      with milder disease (group 2). RESULTS: A high phenotypic variability was found
      among the patients carrying the G85E mutation. This high variability was found
      among patients carrying the same genotype and among siblings. All the studied
      chromosomes carrying the G85E mutation had the 7T variant in the polythymidine
      tract at the branch/acceptor site in intron 8. Of the G85E patients, 25% had
      pancreatic sufficiency and none had meconium ileus, compared with 0% and 32%,
      respectively, of patients from group 1, and 80% and 0%, respectively, from group
      2. Two patients carrying the G85E mutation had sweat chloride levels <60 mmol/L
      whereas all the others had typically elevated levels >80 mmol/L. Compared with
      group 2, patients carrying the G85E mutation were diagnosed at an earlier age and
      had higher sweat chloride levels, with mean values similar to group 1 but
      significantly more variable. Forced expiratory volume in 1 second (FEV1) was
      similar in the three groups, with no differences in the slope or in age-adjusted
      mean values of FEV1. The levels of transcripts lacking exon 9 transcribed from
      the G85E allele measured in 3 patients were 55%, 49%, and 35% and their FEV1
      values were 82%, 83%, and 50% predicated, respectively. CONCLUSIONS: The G85E
      mutation shows variable clinical presentation in all clinical parameters. This
      variability could be seen among patients carrying on the other chromosome the
      same CFTR mutation, and also among siblings. This variability is not associated
      with the level of exon 9 skipping. Thus, the G85E mutation cannot be classified
      either as a severe or as a mild mutation.

PMID- 9271621
TI  - Frequency and necessity of thyroid function tests in neonates and infants with
      congenital hypothyroidism.
AB  - OBJECTIVE: The American Academy of Pediatrics recommends frequent thyroid
      function tests in infants and children with congenital hypothyroidism (CH). Data
      supporting the recommended frequency are lacking. This review was conducted to
      assess the validity of these recommendations. METHODS: The thyroxine (T4) and
      thyroid-stimulating hormone (TSH) levels of 50 neonates diagnosed between 1988 to
      1993 were reviewed to assess the length of time on a specific dose of
      levothyroxine. RESULTS: 1) Changes in the dose of levothyroxine occurred 35 times
      during the first year of life for the 39 children treated with .025 mg/day, five
      times during the first year of life for the 9 children treated with .0375 mg/day,
      and three times during the first year of life for the 2 children treated with
      .050 mg/day. 2) These dose changes occurred at varying time intervals. 3) The T4
      and TSH levels obtained at visits requiring dose changes were statistically
      different from the T4 and TSH levels obtained at the previous two visits. The T4
      and TSH levels at the two visits before the change in dosage did not differ
      statistically. CONCLUSIONS: 1) An initial levothyroxine dose of .0375 mg/day
      requires fewer dose changes than a dose of .025 mg/day. 2) A lack of statistical
      change in T4 or TSH levels obtained at visits before the change-in-dose visit and
      the variable time span between dose changes necessitate frequent monitoring
      regardless of the dose of levothyroxine, the previous T4 or TSH levels, or the
      length of time at a specific dose. 3) These data support the recommendations of
      the American Academy of Pediatrics regarding the frequency of thyroid function
      studies during the first 2 years of life.

PMID- 9271622
TI  - Hemoptysis: a 10-year retrospective study.
AB  - BACKGROUND: Hemoptysis is uncommon in pediatric practice. We reviewed 10 years of
      experience with hemoptysis in a tertiary pediatric hospital to identify patient
      characteristics and predictors of mortality. METHODS: Patients were divided into
      four age groups (0 to 5, 6 to 10, 11 to 20, and >20 years). Hemoptysis was
      defined as mild (<150 mL/day), large (150 to 400 mL/day), or massive (>400
      mL/day). Fever was defined as >/=38.5 degrees C. RESULTS: A total of 228 patients
      (115 males and 113 females) with 246 episodes of hemoptysis were identified and
      grouped according to primary diagnosis. There were 149 patients in the cystic
      fibrosis (CF) group, 37 in the congenital heart disease (CHD) group, and 42 in
      the Other group. Age was significantly higher in the CF group compared with the
      CHD and Other groups. Length of stay was significantly prolonged in the CF group
      compared with the Other group. The overall mortality was 13%. After initial
      analysis, mortality predictors were age, amount of hemoptysis, receipt of blood
      products, and fever. After stratification, we found: 1) in the >20-year age
      group, there was a difference in mortality when comparing CF patients with CHD
      patients; 2) for patients who received blood products, there were differences in
      mortality in patients with CF, CHD, and Other diagnoses; 3) for patients who
      received blood, there were differences in mortality only for the 0- to 5-year age
      group; and 4) the amount of hemoptysis was predictive for mortality only in CHD
      patients. CONCLUSIONS: Hemoptysis presented in young adult CF patients and in
      adolescent CHD patients. Young adult CF patients with hemoptysis had a higher
      risk of mortality compared with young adult CHD patients. The amount of
      hemoptysis predicted mortality only for CHD patients. Receiving blood products
      was predictive of mortality for all patients.

PMID- 9271623
TI  - The effect of insurance status on likelihood of neonatal interhospital transfer.
AB  - OBJECTIVE: To determine the effect of insurance status on the likelihood of
      interhospital transfer for neonates. DESIGN: Population-based retrospective
      cohort study. SETTING: All general acute care nonpediatric hospitals in the five
      counties of southeastern Pennsylvania. PATIENTS: Fifty-six thousand, seven
      hundred eighty-nine infants from 0 to 28 days of age admitted to or born in study
      hospitals between January 1 and December 31, 1991. INTERVENTION: None. MAINS
      OUTCOME MEASURE: Transfer to another general or specialty acute care hospital.
      RESULTS: The incidence (95% confidence interval) of interhospital transfer was
      1.69% (1.60, 1.78). Uninsured infants were nearly twice as likely [relative risk
      (RR) = 1.96 (1.67, 2.31)] to be transferred as commercially insured infants, even
      when adjusted for the effects of prematurity, severity of illness, and the level
      of neonatal intensive care unit in the referring hospital. Similarly, infants
      with Medicaid were more likely to be transferred [RR = 1.20 (1.01, 1.43)] than
      similar commercially insured neonates. Uninsured and publicly insured infants
      were also more likely to be born premature [RR 1.49 (1.39, 1. 60)] than privately
      insured neonates, and were more likely to have both moderate [RR 1.11 (1.04,
      1.23)] and high [RR 1.21 (1.11, 1.32)] illness severity on admission to the
      hospital than privately insured infants. CONCLUSIONS: Neonates with no insurance
      and those with Medicaid coverage were more likely to be transferred than infants
      with private insurance. These results are consistent with those of other
      investigators who have studied financially motivated patient transfers- so-called
      patient dumping-in nonpediatric populations of patients. Our study may represent
      the first documentation of this phenomenon in a pediatric population. Our results
      are also consistent with those of other investigators who have examined the
      effect of insurance status on maternal interhospital transfer, thus providing
      further evidence for the existence of financially motivated transfers within
      regional systems of perinatal care. Future investigation into the effect of
      economic factors on variation in the utilization of transport services, and on
      how transfer influences ultimate patient outcome, is needed as managed care
      health systems become more widespread.

PMID- 9271625
TI  - Chronic cholestatic liver disease with associated tubulointerstitial nephropathy
      in early childhood.
AB  - We report the clinical and morphological features of an unusual hepatorenal
      disorder in 2 patients. The main clinical features were early onset of
      cholestatic liver disease and progressive tubulointerstitial nephritis, leading
      to renal death in early childhood. Renal histology showed interstitial fibrosis,
      tubular atrophy and dilatation, glomerular cysts in the cortex and periglomerular
      fibrosis; liver histology was characterized by portal fibrosis and bile duct
      abnormalities. Evaluating the 12 patients published in the literature, the long
      term prognosis of the liver function appears bad, suggesting the possibility of a
      combined liver and kidney transplantation.

PMID- 9271624
TI  - Tuberculosis transmission among five school bus drivers and students in two New
      York counties.
AB  - OBJECTIVE: Between November 1994 and April 1995, more than 3300 students in 49
      schools in two counties in New York were potentially exposed to five school bus
      drivers with tuberculosis. This investigation was carried out to determine the
      extent of transmission of Mycobacterium tuberculosis among students. METHODS:
      Components of the epidemiologic investigation included tuberculin skin-test
      screening and collection of demographic information for students exposed to a
      driver with tuberculosis, chest radiography and medical evaluation of individuals
      with positive skin tests, and DNA fingerprinting of M tuberculosis isolates. A
      positive skin test was defined as >/=10 mm induration, and a converter was an
      individual with an increase in reaction size of >/=10 mm in the past 2 years.
      RESULTS: The rates of positive skin tests were 0.8%, 0.3%, 9.9%, 1.1%, and 0.7%
      among US-born students exposed to drivers 1 through 5, respectively. The relative
      risk for a positive tuberculin skin test was significant only for students
      exposed to driver 3, and the only secondary case identified among students was
      exposed to driver 3. The DNA fingerprint patterns of isolates from drivers 3 and
      4 matched. CONCLUSION: There was no clear evidence of transmission of M
      tuberculosis to students from drivers 1, 2, 4, or 5. However, evidence suggests
      that driver 3 transmitted M tuberculosis to students and another driver. Routine
      annual tuberculin skin-test screening of drivers would not have prevented these
      tuberculosis exposures.

PMID- 9271626
TI  - Characterization of rainbow trout terminal deoxynucleotidyl transferase structure
      and expression. TdT and RAG1 co-expression define the trout primary lymphoid
      tissues.
AB  - One component of antigen receptor diversity shared by all gnathostomes
      characterized to date is mediated by a unique DNA polymerase, terminal
      deoxynucleotidyl transferase (TdT), which generates significant functional
      diversity during immunoglobulin and T-cell receptor rearrangement. To gain
      further insight into the evolutionary origin(s) of this unique enzyme and the
      immune system, a thymic cDNA clone encoding TdT was isolated from rainbow trout.
      The 2.3 kilobase (kb) full-length clone contained an open reading frame of 1 506
      base pairs with a deduced protein product of Mr 57 000. Sequence comparisons
      demonstrate that TdT has been highly conserved in both sequence (>70% aa
      similarity, >50 aa identity) and overall structure during the course of
      vertebrate evolution. An amino acid alignment of all known TdT sequences
      (chicken, Xenopus, mouse, human, cattle, and trout) reveals that some, but not
      all, structural motifs believed to be critical for TdT activity have been
      conserved. The TdT alignment, in conjuction with the recently solved crystal
      structure for rat beta-polymerase, supports the hypothesis that both may have
      evolved from a common ancestral repair gene. In addition, four PKC
      phosphorylation sites are conserved, and hence may be involved in TdT regulation.
      Because TdT contributes to the generation of junctional diversity in antigen
      receptors of immature lymphocytes, its expression serves as a developmental
      marker for the sites of teleost lymphopoiesis. Northern blot (2.3 kb message)
      analysis shows that TdT mRNA is highly expressed within the thymus and to a
      lesser extent in the pronephros. In addition, reverse transcriptase-polymerase
      chain reaction analysis detected transcipts of both RAG1 and TdT in the thymus,
      pronephros, mesonephros, spleen, and intestine, but not within muscle, liver, or
      brain. Finally, TdT cDNA was amplified from embryos at 20 days post-fertilization
      (pf), which correlates with the appearence of the thymus and pronephros anlage
      during trout ontogeny.

PMID- 9271627
TI  - A highly conserved apoptotic suppressor gene is located near the chicken T-cell
      receptor alpha chain constant region.
AB  - A cosmid clone containing the chicken T-cell receptor alpha chain constant region
      (TCRAC) was sequenced. The cosmid contains the TCRAC gene, six putative joining
      gene segments (TCRAJ), and surprisingly, a chicken homologue for the human
      apoptotic suppressor gene, defender against cell death (DAD1). The DAD1 gene is
      6.3 kilobases downstream of the TCRAC gene and has an inverted transcription
      orientation with respect to the TCRAC gene. The cDNA for the chicken DAD1 gene is
      597 base pairs in length and encodes a highly conserved hydrophobic protein. The
      proximal location of DAD1 to the TCRAC locus has also been confirmed in both
      humans and mouse. The location of the DAD1 gene suggests that DAD1 may play an
      important role in T-cell related apoptotic activities.

PMID- 9271628
TI  - Cloning, structural analysis, and mapping of the B30 and B7 multigenic families
      to the major histocompatibility complex (MHC) and other chromosomal regions.
AB  - We present the cloning, structural analysis, and mapping of new members belonging
      to two multigenic families, the B30-RING finger family and the B7.1-B7.2 family,
      as well as two genes derived by exon shuffling from members of these families.
      Eight new members were found and three of them map to the human major
      histocompatibilitiy complex (MHC) region. Phylogenic and physical mapping
      analysis allowed us to decipher the evolutionary story of these two multigenic
      families and to shed light on the evolution of the MHC region. We also show that
      a deductive analysis can be used to predict the existence of a given gene.

PMID- 9271629
TI  - Polymorphism of chicken CD8-alpha, but not CD8-beta.
AB  - We report here the structural basis of CD8 polymorphism in the chicken. Three
      chicken strains (RPRL Line 7, H.B15.H7, and H.B15. H12) have 14 nucleotide
      differences in the CD8A cDNA sequence causing eight amino acid replacements in
      the extracellular part of the molecule. Only two amino acid replacements and four
      silent mutations were observed in the CD8B cDNA sequence in one (H7) of the
      strains. Substitutions in CD8alpha were solely responsible for the binding of CD8
      specific monoclonal antibodies, as detected by cDNA expression in COS cells. The
      majority of the amino acid substitutions are located in the immunoglobulin V-like
      domain and three of the changes (residues 30, 34, and 58) are situated in the
      putative major histocompatibility complex class I binding CDR1 and CDR2 regions
      of the chicken CD8alpha. CD8A polymorphism has not been reported in other species
      and this suggests that CD8A and CD8B have evolved under different selective
      pressures in the chicken.

PMID- 9271630
TI  - Structure and diversity of the heavy chain VDJ junctions in the developing
      Mexican axolotl.
AB  - The immune capacity of young and adult axolotls (Ambystoma mexicanum) was
      evaluated by examining the combinatorial and junctional diversity of the VH
      chain. A large number of VDJ rearrangements isolated from 2.5-, 3.5-, 10-, and 24
      month-old animals were sequenced. Six JH segments were identified with the
      canonical structure of all known vertebrate JHs, including the conserved Trp103
      Gly104-X-Gly106 motif. Four core DH-like sequences were used by most (80%) of the
      VDJ junctions. These G-rich sequences had structures reminiscent of the TCRB DB
      sequences, and were equally used in their three reading frames. About 25% of the
      Igh, VDJ junctions from 3.5-month-old axolotls were out of frame, but most
      rearrangements were in frame at 10 and 24 months, suggesting that there is active
      selection of the productively rearranged Igh chains in the developing animals.
      There was no significant difference between the size of CDR3 in young (3.5
      months) and subadult (10 months) axolotls (mean: 8.5 amino acids). However, the
      CDR3 loop was 1 amino acid longer in 2-year-old adult animals (mean: 9.5
      residues). Several pairs of identical VDJ/CDR3 sequences were shared between 3.5
      month-old individually analyzed axolotls, or between groups of axolotl of
      different ages. These identical rearrangements might be provided by the selection
      of some B-cell clones important for species survival, although the probability
      that different 3.5-month-old axolotl larvae would produce identical junctions
      seems very low, considering their limited number of B cells (less than 10(5)).
      The high frequency of tyrosine residues and the paucity of charged residues in
      the axolotl CDR3 loops may explain the polyreactivity of natural antibodies, and
      also clarify why it is so difficult to raise specific antibodies against soluble
      antigens.

PMID- 9271631
TI  - HLA class II haplotype and sequence analysis support a role for DQ in narcolepsy.
AB  - A systematic haplotype and sequencing analysis of the HLA-DR and -DQ region in
      patients with narcolepsy was performed. Five new (CA)n microsatellite markers
      were generated and positioned on the physical map across the HLA-DQB1-DQA1-DRB1
      interval. Haplotypes for these new markers and the three HLA loci were
      established using somatic cell hybrids generated from patients. A four-marker
      haplotype surrounding the DQB1(*)0602 gene was found in all narcolepsy patients,
      and was identical to haplotypes observed on random chromosomes harboring the
      DQB1(*)0602 allele. Eighty-six kilobases of contiguous genomic sequence across
      the region did not reveal new genes, and analysis of this sequence for single
      nucleotide polymorphisms did not reveal sequence variation among DQB1(*)0602
      chromosomes. These results are consistent with other studies, suggesting that the
      HLA-DQ genes themselves are among the predisposing factors in narcolepsy.

PMID- 9271632
TI  - Expression of HLA class I molecules assembled with structural variants of human
      beta2-microglobulin.
AB  - Mouse and human beta2-microglobulin (beta2m), which differ by 30% in their
      primary sequence, give rise to disparate levels of HLA class I heavy chain
      expression in transfectants of the beta2m-null FO-1 human melanoma cell line,
      i.e., mouse beta2m directs expression of HLA class I heavy chains that is only
      approximately 20%-30% of that observed for heavy chains assembled with human
      beta2m. In this report we describe our efforts to better understand the
      structural basis of this regulatory phenomenon. Initial insight into the
      importance of the N-terminus of beta2m on HLA expression came from studies with
      FO-1 cells transfected with chimeric (human X mouse) B2m genes. Chimeric beta2m
      molecules containing residues 1-69 from human beta2m and residues 70-99 from
      mouse beta2m (designated HM- beta2m) induced expression of HLA heavy chains to a
      significantly greater extent ( approximately 80% of level observed with cognate
      beta2m) than the reverse chimeric construct (designated MH- beta2m) (10%-15% of
      level observed with cognate beta2m). These data are consistent with the view that
      the major determinants of HLA class I heavy chain expression map to the portion
      of the beta2m molecule which forms the four-stranded beta-pleated sheet,
      comprised of S1, S2, S4, and S5, and one strand of the three-stranded sheet (S3).
      The mapping of class I regulatory sites to the portion of beta2m containing the
      four-stranded beta-pleated sheet supports the interpretation that the heavy chain
      contact residues on beta2m play the major role in regulating major
      histocompatibility (MHC) class I expression. To further dissect beta2m-mediated
      regulation of HLA class I expression, site-directed mutants of beta2m were
      prepared by conversion of human beta2m to the mouse sequence at individual amino
      acid positions within the four-stranded and three-stranded beta-pleated sheets.
      Human to mouse amino acid substitutions were made in each divergent residue
      between positions 1-66, and as controls for COOH-terminal modification, several
      residues between positions 75 and 94. Cytofluorometry with HLA class I-specific
      antibodies indicated that cell surface expression of HLA class I heavy chains was
      largely insensitive to each of the individual substitutions. It is concluded that
      a combination of divergent residues mapping to positions of heavy chain contact
      are responsible for the differences observed in MHC class I expression by
      heterologous forms of beta2m.

PMID- 9271633
TI  - A gene belonging to the Sm family of snRNP core proteins maps within the mouse
      MHC.

PMID- 9271634
TI  - Genetic linkage between the LMP2 and LMP7 genes in the medaka fish, a teleost.

PMID- 9271635
TI  - Allelic repertoire of the human MICB gene.

PMID- 9271636
TI  - Three new polymorphisms in the human complement factor H gene and promoter
      region.

PMID- 9271638
TI  - Two newly identified HLA-DRB1 alleles: DRB1*1322 and DRB1*1327.

PMID- 9271637
TI  - Detection of polymorphisms within the human IL10 receptor cDNA gene sequence by
      RT-PCR RFLP.

PMID- 9271639
TI  - HLA-DRB1*1608: a new HLA-DRB1*16 allele with a short DRB1*03 sequence.

PMID- 9271640
TI  - Description of HLA-A*6803 and A*68N in Mazatecan Indians from Mexico.

PMID- 9271641
TI  - Interventional sialography: a single-center experience.
AB  - PURPOSE: To evaluate interventional sialography for the treatment of chronic
      recurrent sialadenitis due to calculus and/or stricture. METHODS: We performed a
      retrospective review and follow-up of 12 patients treated over a 3-year period.
      The techniques for calculus extraction by papillotomy and basket extraction, and
      stricture dilatation by a combination of predilation with lacrimal dilators and
      then angioplasty balloons are described and the literature is reviewed. RESULTS:
      Follow-up of 1-40 months (mean 14.6 months) showed that 7 of 12 patients remained
      symptom free and 2 others became asymptomatic after an interval. There were no
      major complications from the procedure. CONCLUSION: Interventional sialography is
      a safe and acceptable alternative to surgery and can be considered as first-line
      therapy for symptomatic salivary duct calculus and stricture.

PMID- 9271642
TI  - Per oral balloon sialoplasty: results in the treatment of salivary duct stenosis.
AB  - PURPOSE: To evaluate the results of balloon dilatation of salivary duct stenosis
      and to discuss the technique and its limitations. METHODS: Balloon dilatation of
      30 salivary duct stenoses (24 parotid, 6 submandibular) was carried out in 29
      patients over a 5-year period. Duct dilatation was performed with a 3-mm-diameter
      balloon on a 0.035-inch wire passed into the salivary duct under fluoroscopic
      guidance. The follow-up period ranged from 1 month to 5 years. RESULTS: In 25
      patients balloon dilatation was technically successful in 26 of 30 ducts (87%).
      Ninety-six percent of parotid duct dilatations and 50% of submandibular duct
      dilatations were technically successful. Early clinical follow-up after parotid
      duct dilatation showed that 57% of patients were asymptomatic, 39% showed an
      improvement in symptoms, and 4% showed no improvement in symptoms. Following
      technically successful submandibular duct dilatation (3 cases), 1 patient showed
      complete resolution of symptoms and 1 showed no change in symptoms. No follow-up
      was available for 1 patient. No significant complications were seen. The longer
      term results are presented. CONCLUSION: Balloon dilatation of salivary duct
      stenosis is a simple, safe, and clinically effective method of relieving
      obstructive symptoms of parotid duct stenosis.

PMID- 9271643
TI  - Preoperative embolization of cervical spine tumors.
AB  - PURPOSE: To assess the technical success rate, complications, and effect on
      intraoperative blood loss of preoperative transarterial embolization of cervical
      spine tumors. METHODS: A retrospective analysis was performed on 38 patients with
      tumors of the cervical spine; 69 vertebrae were affected. Polyvinyl alcohol
      particles, coils, gelfoam particles, either alone or in combination, were used
      for preoperative tumor embolization. After embolization a total of 57
      corporectomies with titanium basket implantation were performed. RESULTS: In 36
      of 38 patients, complete (n = 27) or partial (n = 9) embolization was achieved.
      In 23 patients one vertebral artery was completely occluded by coil placement,
      and in one patient the ipsilateral internal and external carotid arteries were
      occluded in addition. No neurological complications could be directly related to
      the embolization, but two postoperative brain stem infarctions occurred. The mean
      intraoperative blood loss was 2.4 L. CONCLUSION: Transarterial embolization of
      cervical spine tumors is a safe and effective procedure to facilitate extensive
      surgery.

PMID- 9271644
TI  - Percutaneous treatment of iliac aneurysms and pseudoaneurysms with Cragg Endopro
      System 1 stent-grafts.
AB  - PURPOSE: To evaluate the feasibility and short-term follow-up results of treating
      iliac aneurysms by the Cragg Endopro System 1 stent-graft. METHODS: Nine lesions
      (two pseudoaneurysms and seven atherosclerotic aneurysms) were treated in eight
      patients by percutaneous implantation of a total of 10 stent-grafts. The
      procedure was followed by anticoagulation with heparin for 6 days, then
      antiplatelet therapy. Follow-up was by color Doppler ultrasound scan at 2 days
      and 3 months after the procedure for all patients, and by venous digital
      subtraction angiography and/or angio-CT up to 12 months later for four patients.
      RESULTS: Initial clinical success rate was 100% and there were two minor
      complications. In one case the delivery system was faulty resulting in failure to
      deploy the stent-graft. An additional device had to be used. At 3-12 months all
      prostheses were patent but one patient (12.5%) had a minimal pergraft leak.
      CONCLUSION: Percutaneous stent-grafting with this device is a safe and
      efficacious treatment of iliac artery aneurysms.

PMID- 9271646
TI  - Stent placement on fresh venous thrombosis.
AB  - PURPOSE: To report on the efficacy of fixing fresh venous thrombus to the venous
      wall by stent placement. METHODS: Seven patients underwent stenting to treat
      acute venous thrombosis. In two patients, the hemodialysis fistula was thrombosed
      with the thrombus extending into the brachial veins. In three patients, the
      hemodialysis fistula was patent but massive swelling of the ipsilateral arm was
      caused by proximal venous thrombosis. Two patients presented with iliac venous
      thrombosis within stented pelvic veins. Stent placement was preceded by other
      mechanical thrombectomy methods in all cases. RESULTS: Attachment of thrombus to
      the venous wall was successful in all cases treated. Acute rethrombosis did not
      occur. Follow-up patency in dialysis patients was 7.2 +/- 2.1 months. One patient
      had rethrombosis of the dialysis graft 3 months after primary treatment. Three
      patients developed restenosis within a mean period of 7.7 months. One shunt
      remained patent for 10 months with no event of reobstruction during follow-up. In
      both patients with iliac stent placement, the vein remained patent over a follow
      up period of 8 and 12 months respectively. CONCLUSION: Stenting fresh venous
      thrombus can achieve immediate venous patency. It may be used as an alternative
      approach when all other percutaneous methods fail. Frequent restenosis within
      stented veins limits its use to very selected cases.

PMID- 9271645
TI  - Brachial artery access for percutaneous renal artery interventions.
AB  - PURPOSE: To evaluate the suitability of transbrachial access for endovascular
      renal artery interventions. METHODS: During 37 consecutive endovascular renal
      artery interventions, the transbrachial approach was used on nine patients (mean
      age 63 years; range 41-76 years) for 11 renal artery procedures on native kidneys
      and one percutaneous transluminal angioplasty (PTA) on a transplanted kidney. The
      reason for using transbrachial access was a steep aorta-renal angle in five, and
      severe aorta-iliac atherosclerosis in the remaining patients. In addition to the
      intervention catheter in the left brachial artery, an additional nonselective
      catheter for controlling the procedure was inserted transfemorally (six patients)
      or via the contralateral brachial artery. RESULTS: Eleven interventions (six
      PTAs, five stents) were successfully completed. The one failure resulted from
      impenetrable subclavian artery stenosis. The only major complication was a
      brachial artery pseudoaneurysm requiring surgical treatment. CONCLUSION:
      Transbrachial access is an effective and relatively safe technique for renal
      artery interventions when transfemoral access is not possible.

PMID- 9271647
TI  - Massive pulmonary embolism: treatment with thrombus fragmentation and local
      fibrinolysis with recombinant human-tissue plasminogen activator.
AB  - PURPOSE: To report the results of thrombus fragmentation in combination with
      local fibrinolysis using recombinant human-tissue plasminogen activator (rtPA) in
      patients with massive pulmonary embolism. METHODS: Five patients with massive
      pulmonary embolism were treated with thrombus fragmentation followed by
      intrapulmonary injection of rtPA. Clot fragmentation was performed with a
      guidewire, angiographic catheter, and balloon catheter. Three patients had
      undergone recent surgery; one of them received a reduced dosage of rtPA. RESULTS:
      All patients survived and showed clinical improvement with a resultant
      significant (p < 0.05) decrease in the pulmonary blood pressure (mean systolic
      pulmonary blood pressure before treatment, 49 mmHg; 4 hr after treatment, 28
      mmHg). Angiographic follow-up in three patients revealed a decrease in thrombus
      material and an increase in pulmonary perfusion. Two patients developed
      retroperitoneal hematomas requiring transfusion. CONCLUSION: Clot fragmentation
      and local fibrinolysis with rtPA was an effective therapy for massive pulmonary
      embolism. Bleeding at the puncture site was a frequent complication.

PMID- 9271648
TI  - Local intraarterial thrombolysis: in vitro comparison of various infusion
      catheters.
AB  - PURPOSE: Catheters are compared in vitro to evaluate the efficacy of thrombolysis
      during urokinase infusion within the thrombus. METHODS: Six catheters were
      introduced individually into human thrombus within a stenotic flow model.
      Urokinase was infused continuously into the thrombus. To quantify the efficacy of
      thrombolysis, pressure gradients were recorded proximal and distal to the
      thrombus and during the course of infusion. Uniformity of lysis was assessed
      radiographically. RESULTS: The fastest and most homogeneous thrombolysis was
      achieved with the EDM and the straight-flush catheter, shown by decreasing
      transthrombotic pressure gradients. All other catheter designs showed less
      homogeneous and delayed thrombolysis (p </= 0.001, Friedmann-Test, Schaich
      Hamerle). There was no significant difference in the efficacy of thrombus
      dissolution between the EDM and the straight-flush catheter (Wilcoxon, matched
      pairs, p > 0.7). CONCLUSION: The EDM catheter and the straight flush catheter
      achieved the most homogeneous and fastest thrombolysis, apparently due to the
      best urokinase distribution within the thrombus.

PMID- 9271649
TI  - Stent treatment of obstructing dissection after percutaneous transluminal
      angioplasty of aortic stenosis caused by nonspecific aortitis.
AB  - We report the follow-up of a patient with nonspecific aortitis (Takayasu's
      disease) in whom a self-expanding stent was used to successfully treat an
      obstructing dissection after percutaneous transluminal angioplasty of a
      descending thoracic stenosis.

PMID- 9271650
TI  - Superselective urokinase infusion therapy for dorsalis pedis artery occlusion in
      Buerger's disease.
AB  - Occlusion of the proximal left dorsalis pedis artery (DPA) in a patient with
      Buerger's disease was treated by continuous urokinase intraarterial infusion
      using a microcatheter. Recanalization of the DPA and healing of a toe ulcer were
      achieved. The patient remains asymptomatic during a 4-year follow-up.

PMID- 9271651
TI  - Partial renal embolization for pediatric renovascular hypertension secondary to
      fibromuscular dysplasia.
AB  - We report a 7-year-old boy with renovascular hypertension showing multiple
      stenoses and microaneurysms of the dorsal branch of the left renal artery caused
      by fibromuscular dysplasia. Hypertension was successfully treated with
      transcatheter alcohol and gelatin sponge embolization of the dorsal branch and
      its distribution. The vertebral branch remained intact. No severe complication
      was encountered. Loss of renal function by renal scintigraphy was minimal. The
      patient remains asymptomatic at 1 year.

PMID- 9271652
TI  - Left lobe recurrent hepatocellular carcinoma treated with lipiodol-TAE via the
      left internal mammary artery.
AB  - A multinodular hepatocellular carcinoma (HCC) was treated with seven
      transarterial interventions via the hepatic artery over a 2-year, 5-month period
      before the eighth angiography showed a recurrent HCC in the anterior portion of
      the left hepatic lobe. The left internal mammary artery (IMA) was feeding the
      tumor. This was successfully treated with Lipiodol-transcatheter arterial
      embolization using a coaxial system via a branch of the left IMA. No
      complications resulted from the procedure. The left IMA should be considered as a
      possible feeding artery to an HCC occurring in the anterior portion of the left
      hepatic lobe.

PMID- 9271653
TI  - Long-term palliative treatment of hepatocellular carcinoma extending into the
      portal vein and bile duct by chemoembolization and metallic stenting.
AB  - We present a patient with hepatocellular carcinoma accompanied by portal vein and
      bile duct tumor thrombi. The patient was treated with a spiral Z-stent covered by
      a polyethylene sheet placed in the bile duct, a Wallstent placed in the portal
      vein, chemoembolization, and external radiation therapy. The patient is alive
      with patency of both endoprostheses 18 months later.

PMID- 9271654
TI  - Successful closure and embolization of a fistula between the pancreatic duct and
      a pseudocyst using ethibloc.
AB  - We successfully achieved complete regression of a pancreatic pseudocyst after
      Ethibloc embolization of a fistula between the cyst and the pancreatic duct.
      Previous treatment by percutaneous drainage over 6 weeks had failed. Treatment
      with a somatostatin analog had not been undertaken.

PMID- 9271655
TI  - Simultaneous thrombolysis of superior mesenteric artery and bilateral renal
      artery thromboembolisms with three transfemoral catheters.
AB  - Successful treatment was achieved for a patient with superior mesenteric artery
      thromboembolism concomitant with bilateral renal artery thromboembolism. Thrombi
      of the three vessels were lysed simultaneously with a three-catheter technique
      using short-term, high-dose urokinase followed by overnight infusion with low
      dose urokinase.

PMID- 9271656
TI  - Percutaneous endoscopic retrieval and replacement of a knitted (Ultraflex)
      biliary stent.
AB  - A knitted (Ultraflex) biliary stent became obstructed after 5 months causing
      recurrent jaundice in a 92-year-old man with pancreatic cancer. The obstructed
      stent was successfully removed percutaneously by retrieval forceps under guidance
      by an 8.4 Fr fiberoptic biliary endoscope. A new stent was placed. No
      complications were encountered.

PMID- 9271657
TI  - Re: Friday afternoon pulmonary arteriography (FAPA): are Fridays good for your
      health?

PMID- 9271658
TI  - Re: Percutaneous treatment of a symptomatic brachiocephalic artery stenosis with
      a Palmaz stent.

PMID- 9271659
TI  - Re: Percutaneous transcatheter embolization for hemorrhage from an empyema
      necessitatis of the thoracic wall.

PMID- 9271660
TI  - Re: Fallopian tube communication after percutaneous abdominal abscess drainage.

PMID- 9271662
TI  - Sooty foot, a novel mouse mutation that affects the pigmentation of exposed skin,
      but not hair, maps to chromosome 2.
AB  - We have characterized a novel recessive mouse mutation, named sooty foot, that
      increases the pigmentation of the exposed skin on the foot pads, the genital
      region, around the snout and muzzle, the ears, and the tail. By contrast, the
      pigmentation of the hair is unaffected. We have localized the mutation to
      Chromosome 2 by polymerase chain reaction (PCR) amplification of simple sequence
      repeats from pooled DNA from backcross progeny. In an extended backcross we have
      generated a detailed map of the region around sooty foot.

PMID- 9271664
TI  - Confirmation of maternal transmission ratio distortion at Om and direct evidence
      that the maternal and paternal "DDK syndrome" genes are linked.
AB  - The polar, preimplantation-embryo lethal phenotype known as the "DDK syndrome" in
      the mouse is the result of the complex interaction of genetic factors and a
      parental-origin effect. We previously observed a modest degree of transmission
      ratio distortion in favor of the inheritance of DDK alleles in the Ovum mutant
      (Om) region of Chromosome (Chr) 11, among offspring of reciprocal F1-hybrid
      females and C57BL/6 males. In this study, we confirm that a significant excess of
      offspring inherit DDK alleles from F1 mothers and demonstrate that the preference
      for the inheritance of DDK alleles is not a specific bias against the C57BL/6
      allele or a simple preference for offspring that are heterozygous at Om. Because
      none of the previous genetic models for the inheritance of the "DDK syndrome"
      predicted transmission-ratio distortion through F1 females, we reconsidered the
      possibility that the genes encoding the maternal and paternal components of this
      phenotype were not linked. We have examined the fertility phenotype of N2 females
      and demonstrate that the inter-strain fertility of these females is correlated
      with their genotype in the Om region. This result establishes, directly, that the
      genes encoding the maternal and paternal components of the DDK syndrome are
      genetically linked.

PMID- 9271663
TI  - Interval mapping and congenic strains for a blood pressure QTL on rat chromosome
      13.
AB  - The renin locus (Ren) on rat Chromosome (Chr) 13 had previously been shown to
      cosegregate with blood pressure in crosses involving Dahl salt-sensitive (S) and
      Dahl salt-resistant (R) rats. In the present work, interval mapping of blood
      pressure on Chr 13 with a large F2 (S x R), n = 233, population yielded a maximum
      LOD = 4.2 for linkage to blood pressure, but the quantitative trait locus (QTL)
      was only poorly localized to a large 35-centiMorgan (cM) segment of Chr 13. In
      the linkage analysis, the S-rat QTL allele (S) was associated with higher, and
      the R-rat QTL allele (R) with lower blood pressure, the difference between
      homozygotes being about 20 mm Hg. A congenic strain was made by introgressing the
      R-rat Ren allele into the recipient S strain. This congenic strain showed a 24 mm
      Hg reduction (P = 0.004) in blood pressure compared with S rats for rats fed 2%
      NaCl diet for 24 days; this difference was confirmed by two other independent
      tests. Two congenic substrains were derived from the first congenic strain with
      shorter R Chr 13 segments on the S background. Comparisons among these congenic
      strains showed that a blood pressure QTL was in the 24-cM chromosomal segment
      between Syt2 and D13M1Mit108. This segment does not include the renin locus,
      which is thus excluded from being the gene on rat Chr 13 responsible for genetic
      differences in blood pressure detected by linkage analysis.

PMID- 9271665
TI  - A new allele of the lurcher gene, lurcherJ.
AB  - A new neurological mouse mutation that arose spontaneously in a BALB/cByJ stock
      displays a semidominant pattern of inheritance. In the heterozygote, this
      mutation results in an early loss of Purkinje cells in the cerebellum, which is
      followed by the overt symptom of an ataxic gait first observed at postnatal day
      13 (P13). A portion of animals homozygous for the mutation die within P0; the
      remaining homozygotes die by P25. The mutation maps to mouse Chromosome (Chr) 6
      between markers D6Rck314 and D6Rck361, a chromosomal segment that contains the
      lurcher (Lc) locus. The Lc mutation is also semidominant and has a strikingly
      similar phenotype. A cross between a new mutant (Nm) heterozygote and an Lc
      heterozygote yields double heterozygotes, animals that carry both mutations, with
      a phenotype similar to that of both Nm and Lc homozygotes. The similarity in
      phenotype, the colocalization of the two loci on mouse Chr 6, and the positive
      result of the allelism test demonstrate that the new mutation is an allele of the
      Lc gene.

PMID- 9271666
TI  - Characterization of the mouse beta-prime adaptin gene; cDNA sequence, genomic
      structure, and chromosomal localization.
AB  - Adaptins are important subunits of heterotetrameric complexes called adaptors,
      which participate in the clathrin-coated, vesicle-mediated endocytosis and
      intracellular receptor transport. The gene family of adaptins is divided into
      three classes, alpha, beta, and gamma, with further subdivision into beta- and
      beta-prime components. Two beta-prime adaptins, the rat AP105a and the human
      BAM22, have previously been characterized. The BAM22 gene is located on human
      Chromosome (Chr) 22q12 and can be considered a candidate meningioma tumor
      suppressor gene. We report here the characterization of the mouse ortholog of the
      BAM22 gene, and we suggest the name adtb1 for the mouse gene. Like the BAM22
      gene, the adtb1 transcript is highly and ubiquitously expressed. We provide 3885
      bp cDNA sequence, which entirely covers the open reading frame of the adtb1,
      capable of encoding a protein of 943 amino acids. The adtb1 protein is highly
      conserved (>96% identity) when compared with AP105a and BAM22 proteins. We also
      report the genomic organization of adtb1, which is similar to the BAM22 gene. The
      adtb1 gene has been assigned to mouse Chr 11, band 11A2, which confirms the
      synteny between human Chr 22q12 and mouse Chr 11.

PMID- 9271668
TI  - Chromosomal localization of rat hepatocyte growth factor (Hgf) and HGF receptor
      (Met) and characterization of HGF receptor cDNA.
AB  - The Met protooncogene encodes the tyrosine kinase receptor for the hepatocyte
      growth factor (HGF), a potent mitogen for hepatocytes and other epithelial cells
      produced by mesenchymal cells. Many of the studies on the physiologic and
      neoplastic growth of the liver, as well as other organs, have been performed in
      the rat. Therefore, chromosomal mapping of the rat Hgf gene and the gene of its
      receptor is of particular value. To achieve this, a probe of the coding part of
      rat HGF cDNA was used to isolate four genomic probes from a lambda phage rat
      genomic library. These probes were used to map the Hgf gene to Chromosome (Chr)
      4q12 by the FISH technique. To obtain a probe for the mapping of the HGF
      receptor/Met gene, we cloned the complete coding region of the rat HGF receptor
      mRNA. Complementary DNA (cDNA) was synthesized with reverse transcriptase from
      total RNA for use as a template for the PCR. The two PCR primers were designed
      based on human and mouse sequences and were located in the flanking regions of
      the open reading frame of the HGF receptor mRNA. Amplification resulted in a band
      of an estimated size of 4.1 kb, which was cloned and sequenced. The nucleotide
      sequence showed about 93% and 85% homology compared with mouse and human HGF
      receptor sequences, respectively. A full-length probe of the coding part of the
      cDNA was used to map the rat HGF receptor/Met gene to Chr 4q21 by the FISH
      technique. Therefore, the rat Hgf and HGF receptor/Met genes are located
      relatively close to each other, in a way similar to humans but not mice.

PMID- 9271667
TI  - Rat chromosome 1: regional localization of seven genes (Slc9a3, Srd5a1, Esr,
      Tcp1, Grik5, Tnnt3, Jak2) and anchoring of the genetic linkage map to the
      cytogenetic map.
AB  - Seven genes were regionally localized on rat Chromosome (Chr) 1, from 1p11 to
      1q42, and two of these genes were also included in a linkage map. This mapping
      work integrates the genetic linkage map and the cytogenetic map, and allows us to
      orient the linkage map with respect to the centromere, and to deduce the
      approximate position of the centromere in the linkage map. These mapping data
      also indicate that the Slc9a3 gene, encoding the Na+/H+ exchanger 3, is an
      unlikely candidate for the blood pressure loci assigned to rat Chr 1. These new
      localizations expand comparative mapping between rat Chr 1 and mouse or human
      chromosomes.

PMID- 9271669
TI  - Cloning and mapping of a human and mouse gene with homology to ecto-ATPase genes.
AB  - The human CD39-like-1 gene (CD39L1) was isolated from a selected cDNA library
      enriched for transcripts from regions of human Chromosome (Chr) 9q. Database
      searches with sequences of one group of clones from the selected cDNA library
      showed strong amino acid homology to the lymphoid cell activation antigen CD39,
      an ecto-apyrase gene from human and mouse. The full-length sequence for CD39L1
      identified a putative 472 amino acid protein with greater than 60% identity with
      the chicken muscle ecto-ATPase protein, as well as homology to a number of other
      known ecto-ATPases and ecto-apyrases from rat, garden pea, yeast, and Toxoplasma
      gondii. A high level of amino acid identity suggests that CD39L1 is closely
      related to the chicken muscle ecto-ATPase. The presence of the human ABC2 gene on
      an overlapping cosmid and hybridizations to somatic cell mapping panels suggest
      that CD39L1 maps to human Chr 9q34. A mouse homolog was isolated (showing greater
      than 78% nucleotide sequence identity) and mapped by FISH to mouse Chr 2, the
      syntenic region of human 9q34. The genomic structure of CD39L1 reveals 9 exons
      covering less than 7 kb.

PMID- 9271670
TI  - IAP insertion in the murine LamB3 gene results in junctional epidermolysis
      bullosa.
AB  - The laminin-5 molecule functions in the attachment of various epithelia to
      basement membranes. Mutations in the laminin-5-coding genes have been associated
      with Herlitz junctional epidermolysis bullosa (HJEB), a severe and often lethal
      blistering disease of humans. Here we report the characterization of a
      spontaneous mouse mutant with an autosomal recessive blistering disease. These
      mice exhibit sub-epithelial blisters of the skin and mucosal surfaces and
      abnormal hemidesmosomes lacking sub-basal dense plates. By linkage analysis the
      genetic defect was localized to a 2-cM region on distal Chromosome (Chr) 1 where
      a laminin-5 subunit gene, LamB3, was previously localized. LamB3 mRNA and laminin
      5 protein were undetectable by Northern blot analysis and immunohistochemical
      methods, respectively. DNA sequence analysis indicated that the LamB3 genetic
      defect resulted from disruption of the coding sequence by insertion of an
      intracisternal-A particle (IAP) at an exon/intron junction. These findings
      suggest a role for laminin-5 in hemidesmosome formation and indicate that the
      LamB3(IAP) mutant is a useful mouse model for HJEB.

PMID- 9271672
TI  - Genomic organization and chromosomal localization of the mouse snail (Sna) gene.

PMID- 9271671
TI  - Genetic and physical mapping of the mouse host resistance locus Lgn1.

PMID- 9271673
TI  - The structure of DXF34, a human X-linked sequence family with homology to a
      transcribed mouse Y-linked repeat.

PMID- 9271674
TI  - Structure of the human UGT2B4 gene encoding a bile acid UDP
      glucuronosyltransferase.

PMID- 9271676
TI  - Linkage mapping of Sax2 to mouse chromosome 5.

PMID- 9271675
TI  - Murine Hn1 on chromosome 11 is expressed in hemopoietic and brain tissues.

PMID- 9271677
TI  - The mouse semaphorin F (Semaf) maps to chromosome 15.

PMID- 9271678
TI  - Assignment of the murine inwardly rectifying potassium channel IRK3 gene (Kcnj4)
      to the mouse chromosome 15.

PMID- 9271679
TI  - The genes encoding glucokinase regulatory protein and ketohexokinase co-localize
      to mouse chromosome 5.

PMID- 9271680
TI  - Kallikrein binding protein (KBP) maps to rat chromosome 6 but does not
      cosegregate with blood pressure in a GH x BN cross.

PMID- 9271681
TI  - Mapping of the rat and mouse nicotinamide nucleotide transhydrogenase gene.

PMID- 9271682
TI  - Fluorescent in situ mapping of the murine deleted in split hand/split foot 1
      (dss1) gene to chromosome 6.

PMID- 9271683
TI  - STAT5A encoding gene maps to chromosome 19 in cattle and goat and to chromosome
      11 in sheep.

PMID- 9271684
TI  - Mapping of the galectin-3 gene (LGALS3) to human chromosome 14 at region 14q21
      22.

PMID- 9271685
TI  - Localization of the gene encoding a novel isoform of lysyl hydroxylase.

PMID- 9271687
TI  - Prevention of HIV transmission.
AB  - Primary care physicians continue to play an important role in preventing HIV
      transmission by targeting messages to their high-risk patients. The risk of HIV
      transmission cannot be eliminated entirely; however, clinicians have a variety of
      prevention interventions at their disposal. Behavioral and therapeutic
      interventions offered in a client-centered environment have the greatest chance
      of success. Patients can benefit from individualized prevention plans that
      decrease risk by treating drug addiction and by modifying sexual and drug-taking
      behaviors. The risk of HIV infection in health care workers can be reduced by
      strict adherence to universal precautions and the use of postexposure
      antiretroviral therapy.

PMID- 9271688
TI  - HIV/AIDS. Assessment, testing, and natural history.
AB  - Physicians need to screen all patients for HIV risk and provide education to
      reduce risk. If a careful history and physical examination suggest the
      possibility of HIV infection, physicians should provide informed consent, counsel
      appropriately, and perform testing. For patients testing positive, knowledge of
      HIV pathogenesis helps physicians devise rational plans for treatment and patient
      education. The nonspecific symptoms of primary HIV infection cause it to be
      underrecognized and frequently not evaluated appropriately. Therapeutic
      intervention during primary infection may present a unique opportunity to
      attenuate disease caused by HIV.

PMID- 9271689
TI  - The initial assessment of the HIV-infected patient.
AB  - The initial assessment of the patient with HIV disease requires clinical staging,
      identification of HIV-related and nonrelated illness, discussion of specific
      psychosocial issues, initiation of the process of patient education, and
      initiation of a sustained partnership between patient and clinician. The clinical
      content of the assessment depends on knowledgeable history-taking, focused
      physical examination, and specific laboratory tests. Partnering increases the
      likelihood of early recognition of important signs and symptoms and the
      institution of appropriate therapeutic measures. Successful and satisfying
      clinician-patient relationships help produce better patient outcomes.

PMID- 9271690
TI  - Ongoing care of the patient with HIV/AIDS.
AB  - Because patients with HIV are living longer, health maintenance and disease
      prevention have become important aspects of care. Clinical use of CD4 cell counts
      and viral load assays to monitor disease progression is reviewed. This article
      discusses the effect malnutrition has on disease progression and interventions to
      prevent wasting syndrome. Resources for patient education are identified that
      enhance the patient's ability to make informed decisions about his or her health
      care. Supportive services should be used to maintain a patient's independence.
      These programs also may provide emotional and financial stability and legal
      assistance if required.

PMID- 9271691
TI  - HIV/AIDS management in office practice. Antiretroviral therapy.
AB  - Treatment of HIV with nucleoside analog reverse transcriptase inhibitors (RTIs)
      and protease inhibitors forms the backbone of anti-HIV therapy. Non-nucleoside
      RTIs, immune modulators, and new entries in existing classes of pharmacologic
      agents hold promise for the future. Combination therapy with two, three, or more
      agents has become the standard of care, although additive toxicities often can be
      dose-limiting. Increases in the understanding of viral dynamics have introduced
      measures of systemic viral burden into clinical practice, and viral load
      considered in combination with CD4 lymphocyte numbers guides decisions about
      initiating and modifying antiviral therapy.

PMID- 9271693
TI  - Neurologic complications of HIV infection.
AB  - Neurologic symptoms are common in HIV-infected individuals, and they result from
      a wide range of etiologic agents, including HIV itself and opportunistic
      pathogens. Neurologic syndromes may be presenting features or may occur at any
      stage of infection, and they affect all levels of the neuraxis. The physician who
      cares for patients with AIDS must be prepared to recognize these neurologic
      complications to pursue aggressive diagnosis and, where possible, therapeutic
      interventions. The possibility of concurrent or unusual pathogens and atypical
      presentations make care of the AIDS patient with neurologic disease a challenging
      exercise that requires informed analysis and thoughtful clinical judgment.

PMID- 9271692
TI  - Prevention and treatment of common HIV-associated opportunistic complications.
AB  - This article reviews the importance of preventing illness in HIV-infected
      patients. The indications and medication regimens for preventing several common
      opportunistic complications are discussed. Infections addressed include
      pneumocystis pneumonia, Mycobacterium avium complex, toxoplasmosis encephalitis,
      and tuberculosis, among others. Other preventive interventions such as routine
      immunizations are addressed briefly as well. Diagnosis and treatment of five of
      the most common HIV-associated opportunistic infections are reviewed.

PMID- 9271694
TI  - Symptom management in HIV-infected patients.
AB  - HIV infection predisposes patients to many opportunistic infections that can be
      treated readily once they are diagnosed. Diagnosis is sometimes difficult because
      these complications may be unfamiliar, and even familiar diseases present
      atypically in the setting of HIV. Several clinical syndromes that are common in
      HIV patients are described. Discussion of each syndrome includes differential
      diagnosis, diagnostic evaluation, and interval symptomatic treatment to alleviate
      distress, pending definitive treatment.

PMID- 9271695
TI  - Palliative medicine and HIV/AIDS.
AB  - This article provides an introduction to the field of palliative medicine as it
      applies to the care of HIV/AIDS. Issues of pain management, end-of-life care,
      ethics, and bereavement are discussed with the intention of providing the primary
      care physician additional resources in the provision of care to patients with
      HIV/AIDS.

PMID- 9271696
TI  - Women and HIV. A review of current epidemiology, gynecologic manifestations, and
      perinatal transmission.
AB  - HIV is increasing rapidly in women, particularly due to heterosexual
      transmission. The manifestations of HIV in women differ in some respects from
      those in men, most obviously with respect to gynecologic manifestations.
      Candidiasis, anogenital human papillomavirus and neoplasia, and contraception and
      prevention of sexual transmission are all important issues. Reduction in
      perinatal transmission is a key focus in women, with a growing number of
      effective preventative interventions.

PMID- 9271697
TI  - The clinical management of children perinatally exposed to HIV.
AB  - The spread of the HIV/AIDS epidemic to children has become one of the most
      serious public health problems in the United States. This article presents the
      clinician with an overview of the epidemiology of HIV/AIDS among infants and
      children, discusses major issues about the prevention of perinatal HIV
      transmission (including ZDV prophylaxis), and presents the management and
      treatment issues of HIV infection among children.

PMID- 9271698
TI  - Primary care of the HIV-seropositive chemically dependent patient.
AB  - Persons with chemical dependency problems account for a large and growing number
      of cases of HIV/AIDS in the United States. This group poses unique challenges as
      providers address their medical and psychosocial needs. Although much of the care
      of substance-using HIV patients is the same as that of non-substance-using
      patients, differences do exist. Treatment of the underlying chemical dependency
      is a cornerstone of caring for these patients.

PMID- 9271699
TI  - Caregivers and HIV infection. Services and issues.
AB  - Because of the complexity of their illness, patients infected with HIV may
      require many services to facilitate the management of the disease. The primary
      care provider must understand and facilitate the services that are needed and
      needs to be familiar with the individuals responsible for the care of each
      patient. There are many stresses that have been identified in HIV caregiving, for
      informal caregivers and health care workers. These stresses are described, and
      suggestions for appropriate interventions are outlined.

PMID- 9271700
TI  - Occurrence of DNA sequence differences in C-heterochromatin of Eulemur coronatus
      and Eulemur macaco, as revealed by fluorescence resonance energy transfer.
AB  - In the genus Eulemur (Malagasy lemurs) karyotype diversification has occurred
      mainly through Robertsonian mechanisms of chromosome fusion (Rumpler et al.,
      1976). Eulemur coronatus is the sole species to have the largest genome size, due
      to a very large amount of C-heterochromatin, mostly located at the
      pericentromeric regions of the largest chromosomes (Warter and Rumpler, 1985).
      This increase in C-heterochromatin was thought to be due to DNA amplification
      (Ronchetti et al., 1993). The aim of this work was to investigate whether the
      large C-heterochromatin of Eulemur coronatus might have derived by amplification
      of the smaller C-heterochromatin of Eulemur macaco, a closely related species
      with smaller genome size. To obtain information on the overall base composition
      of the total genomes, on the relative interspersion of AT and GC base paris along
      the DNA molecule and on the structural differences in C-heterochromatin, we used
      a quantitative cyto-chemical approach, based on fluorescence resonance energy
      transfer (FRET) between DNA-specific fluorochromes (i.e. the AT-specific Hoechst
      33258, and the non base-specific dye, propidium iodide). Micro-spectrofluorometry
      and image analysis were used to investigate both the overall FRET efficiency and
      its spatial distribution along the chromosome arms. FRET efficiency values of the
      DNA in C-heterochromatin were significantly different in the two Eulemur species,
      indicating a different qualitative composition of repetitive DNA. This suggests
      that the repetitive DNA of Eulemur coronatus cannot have originated by
      amplification in toto of the repetitive DNA sequences of Eulemur macaco.

PMID- 9271701
TI  - Contribution of confocal laser scanning microscopy to glycochemistry of mouse and
      rat submandibular glands by single and double lectin staining.
AB  - The localization of individual glycosidic residues in the mouse and rat
      submandibular glands was examined using confocal laser scanning microscopy
      (CLSM). For these organs we tested some procedures of fixation and embedding to
      better understand the distribution of some lectin-probes inside well preserved
      secretory cells and observed that fixation and inclusion steps did not influence
      appreciably the location and intensity of the reactive sites. The fixation
      mixture of 4% paraformaldehyde, 1% glutaraldehyde and 0.2% picric acid produced
      the most satisfactory results. In specimens labeled with PNA-, Con A-, LTA-FITC
      and WGA-, DBA-TRITC lectins, the convoluted granular tubules (CGT) proved to be
      composed of secretory granules with high-density lectin labeling. The complex
      organization of secretory glycocomponents within the granule matrix was further
      resolved by double labeling and dual scanning experiments. Some lectins exhibited
      colocalization while others displayed differential localization providing
      information about the occurrence of O- and N-linked glycoconjugates. The CLSM
      technique applied to fluorochrome-conjugated lectins also revealed a more marked
      dimorphism in the rat rather than in the mouse submandibular gland. In
      particular, the male rat submandibular gland was found to consist of CGT
      heterogeneous cell populations, while the mouse submandibular gland did not show
      glycochemical differences between cells. Female rats exhibited a lectin profile
      very different from that of female mouse.

PMID- 9271702
TI  - AgNOR protein quantity of cervical smears correlates with that of histological
      sections in cervical intraepithelial neoplasia.
AB  - The quantitative distribution of AgNOR proteins has been determined by image
      cytometry in 52 cervical smears obtained from normal cervix (n = 20), grade I CIN
      (cervical intraepithelial neoplasia) (n = 3), grade II CIN (n = 5) and grade III
      CIN (n = 24). No significant difference was demonstrated in the mean AgNOR
      protein area values between normal cervix, CIN I and CIN II, while AgNOR protein
      scores of CIN III were significantly greater than those of normal cervix (p <
      0.05). AgNOR protein quantity was also determined in 17 colposcopic directed
      biopsies of patients with CIN lesions (3 CIN II and 14 CIN III) already studied
      by cytological analysis. When AgNOR protein values of histological sections and
      corresponding cytological smears were compared by linear regression analysis, a
      significant correlation was found (r = 0.74, p < 0.05). Our results demonstrate
      that AgNOR protein quantity of cervical smears actually reflects that of the
      cervical epithelium in situ and may therefore be useful for the cytological
      diagnosis of cervical lesions.

PMID- 9271704
TI  - Calcitonin gene-related peptide immunoreactivity in adult mouse lung.
AB  - Calcitonin gene-related peptide (CGRP) is a 37 amino acid peptide coded by the
      calcitonin gene that is produced by thyroid C cells and medullary carcinoma. It
      is also widely distributed in neurons and endocrine cells throughout the body.
      The presence of CGRP in the lungs suggests that this peptide exerts important
      regulatory actions at this level, and it can act like a neuroregulator released
      both from nerve terminals and neuroendocrine (NE) cells. To understand the role
      of CGRP in the lung, it is important to explore its localization in different
      species. In this paper, we analyse the presence and localization of CGRP in the
      adult mouse lung using an immunocytochemical staining method. Our results show a
      widespread distribution of this peptide in isolated neuroendocrine cells and
      neuroepithelial bodies (NEBs), as well as in nerve fibres distributed in many
      areas of the lung, including bronchi and bronchioli. These fibres are in close
      contact with epithelium, neuroendocrine cells and smooth muscle. In addition,
      some immunostained nerve cell bodies and immunoreactive intrinsic ganglion cells
      can be shown. CGRP has been previously demonstrated in the mammalian lung using
      immunocytochemistry. To the best of our knowledge, this is the first time that
      CGRP has been immunocytochemically demonstrated in the mouse lung both in NE
      cells, NEBS, ganglion cells and in nerve fibres which are related to
      neuroendocrine cells.

PMID- 9271703
TI  - Differences in AgNOR quantity between colorectal cancer and corresponding
      metastases: are they useful for prognostic purposes?
AB  - In order to evaluate the relationship between primary colorectal adenocarcinomas
      and their metastases with regard to AgNOR proteins expression, we have performed
      a morphometric analysis of AgNOR silver precipitates (AgNORs) in advanced
      colorectal carcinomas (stage III-IV) as well as in corresponding lymph node and
      distant metastases. Surgical specimens studied consisted of 64 primary tumours,
      56 lymph node and 43 hepatic or omental metastases; for each formalin-fixed
      paraffin-embedded specimen, silver staining according Ploton et al. (1986) was
      performed and the AgNOR area (NORA) relative to primary site, lymph node and/or
      distant metastases was calculated. A significant difference (P < 0.001) among the
      non-neoplastic colonic control mucosae and primary or metastatic neoplastic
      lesions was found, but no statistically significant differences were encountered
      among the categories of primary colorectal carcinomas and their lymph node or
      distant metastases. Moreover, on the basis of NORA data case per case, three
      groups of patients were selected. In particular, in the group 1 NORA values of
      metastases were higher than those of the corresponding primary carcinomas, while
      in the group 2, NORA values of metastases were lower than those of the
      corresponding primary neoplasms; no differences of NORA values were encountered
      in group 3. The cumulative patient survival estimated by the Kaplan-Meier method
      showed a worse prognosis for patients belonging to group 1, where higher AgNOR
      values, not only in primary carcinomas but also in lymph node and distant
      metastases, were found.

PMID- 9271705
TI  - Constitutive expression of heat shock proteins 70 and 90 in rat cerebellum.
AB  - Exposure to heat shock and other stressful conditions activates in cells of all
      organisms a specific genetic program. This enhances the synthesis of proteins
      with a protective role against cellular damage, called heat shock proteins
      (hsps). Furthermore, in the mammalian nervous system, a considerable amount of
      hsps is also synthesized under normal conditions suggesting that they play an
      important role in the metabolism of unstressed cells. In this study we analysed
      the constitutive expression of proteins belonging to the hsp70 and hsp90 family
      in the rat cerebellum using immunocytochemistry with specific monoclonal
      antibodies. Our results showed that an intense immunostaining was evident, but
      was restricted in certain distinct cerebellar areas only, while no differences in
      the distribution of the two hsps were found. The strongest response was detected
      in the Purkinje neurons but deep cerebellar nuclei were also positive. In no case
      glial cells were found to be reactive for hsps despite their strong response for
      specific markers like glial fibrillary acid protein (astrocytes) and cyclic
      nucleotide phosphodiesterase (oligodendrocytes). These data indicate that both
      the hsp70 and hsp90 family have fundamental physiological functions in cerebellar
      neurons while they seem to play only a minor role in the metabolism of glial
      cells.

PMID- 9271706
TI  - Prognostic role of cyclin D1 in non small cell lung cancer: an
      immunohistochemical analysis.
AB  - Lung cancer is a worldwide problem and in many countires it is the most lethal
      malignancy. Because relapse is frequent after resection of non small cell lung
      cancer, an urgent need exists to define prognostic factors which could help in
      choosing the best therapeutic approach. We performed immunohistochemistry on 60
      formalin-fixed paraffin-embedded non small cell lung cancer specimens in order to
      evaluate the frequency of cyclin D1 overexpression, and to relate it to the
      degree of malignancy of these tumors and to the overall survival time of the
      patients. All specimens were positive for cyclin D1 immunostaining. We found
      cyclin D1 overexpression in 30 (50%) of our specimens, with no significant
      difference among the different histological types. Cyclin D1 overexpression
      correlates in a statistical manner with short-term patient survival. Mantel-Cox
      analysis of these data generated a significant P value = 0.003. The mean survival
      time and the five-year survival rate also differed statistically. We did not find
      any statistically significant correlation between cyclin D1 overexpression and
      histological grading, tumor stage or TNM status. We concluded that cyclin D1
      overexpression in 30 patients is a frequent event in non small cell lung cancer
      pathogenesis and may have prognostic relevance.

PMID- 9271707
TI  - Histochemical distribution and accumulation of trace metals in the heart of green
      and normal Crassostrea angulata specimens from different southwest Spanish
      coasts.
AB  - Histochemical distribution and quantification of trace metals (copper-Cu-, zinc
      Zn- and iron-Fe-) were studied in oyster, Crassostrea angulata heart (auricle and
      ventricle) from different southwest Spanish coasts. In green Crassostrea angulata
      specimens (green coloration in gills and visceral mass), numerous brown cells
      (blackish-brown) were observed in the wall of the auricles and dispersed by
      connective tissue, where inflammatory lesions related with granular amoebocytes
      were observed. However, only a few brown cells (translucent ligh-brown) were
      detected in auricles of normal oysters. Histochemically, Fe, Cu and Zn granules
      were observed in the wall of the heart (auricles), in brown cells, as well as in
      the granular amoebocytes, which are increased in green Crassostrea specimens.
      Auricle brown cells reacted weakly with PAS and Alcian Blue techniques. These
      cells contain proteins, as well as cysteine and cystine groups; these residues (
      SH and S-S) being very abundant in the heart of green specimens, specially in
      brown cells and in granular amoebocytes. Lipofuscin granules were detected in
      these brown cells and in granular amoebocytes. On the other hand, in the heart
      (normal and green specimens), Zn levels were higher than Fe and Cu concentrations
      and heavy metals analyzed were lower in heart of normal than in green specimens.
      In green specimens, Cu and Zn levels were higher in auricles than in ventricles.

PMID- 9271708
TI  - Exact transmission-disequilibrium tests with multiallelic markers.
AB  - The transmission-disequilibrium (TD) test is a powerful method for detecting
      linkage between marker and disease loci in the presence of linkage
      disequilibrium. For multiallelic markers, we propose the use of exact tests,
      which are implemented using both an exact algorithm and Markov chain Monte Carlo
      simulation. Simulation studies show that exact tests improve both the small
      sample validity and the power of the TD method. We also compared the usual single
      affected-offspring sampling scheme to one in which pairs of affected siblings are
      sampled. Affected-sib-pair sampling greatly increases the power of the TD method
      and will be most useful when a sample of affected sib pairs is available from
      prior linkage studies.

PMID- 9271709
TI  - Comparison of methods for analyzing binary data arising from two-sample twin
      studies.
AB  - The study of twins is widely used for research into genetic and environmental
      influences on human outcome measurements. For the study design in which
      independent samples of monozygotic and dizygotic twins are compared with respect
      to their similarity on a binary trait, several statistical methods have been
      proposed. Using a Monte Carlo simulation, we compare the five following
      procedures: 1) goodness-of-fit method based on the common correlation model, 2)
      normal approximation of the maximum likelihood estimators of the common
      correlation coefficients, 3) Ramakrishnan et al. [(1992) Genet Epidemiol 9:273
      282] method of odds ratio comparison, 4) generalized estimating equations method
      of odds ratio estimation, and 5) tetrachoric correlation method. The results show
      that the goodness-of-fit approach has similar or better performance in both type
      one error rates and power than the other methods in all parameter settings. Its
      advantage with respect to type-one error rates is particularly clear under
      conditions of small sample sizes, extreme prevalences, or high values of the
      intraclass correlation coefficients. Therefore, the goodness-of-fit method is
      recommended for the two-sample twin study design.

PMID- 9271710
TI  - Population-based family study designs: an interdisciplinary research framework
      for genetic epidemiology.
AB  - Most complex traits such as cancer and coronary heart diseases are attributed
      either to heritable factors or to environmental factors or to both. Dissecting
      the genetic and environmental etiology of complex traits thus requires an
      interdisciplinary research strategy. Genetic studies generally involve families
      and investigate familial aggregations of traits, segregation of major disease
      genes, and locations of disease genes on the human genome, the latter of which
      can be identified via linkage analysis. Epidemiologic studies often use
      population-based case-control studies to establish the role of specific
      environmental factors. Integrating both objectives, genetic epidemiology is to
      assess the associations of environmental factors with disease status, to quantify
      the aggregation of cases within families, to characterize putative disease genes
      via segregation analysis, and to localize disease genes via linkage analysis with
      genetic markers. To accomplish these objectives through designed studies, we
      propose a class of population-based family study designs, which are formed by
      choosing among sampling designs at three stages. The objectives of sampling at
      these three stages are 1) combined aggregation and association analysis, 2)
      combined segregation, aggregation, and association analysis, and 3) combined
      linkage, segregation, aggregation, and association analysis. These designs form
      an interdisciplinary research framework for genetic epidemiology. Our preliminary
      exploration of this framework and related analytic methods indicates that
      population-based family study designs retain the efficiency of linkage analysis
      for localizing disease genes without losing the property of being population
      based, and they will therefore allow an assessment of a joint contribution of
      genetic and environmental factors to complex traits.

PMID- 9271711
TI  - Linkage analysis of complex traits using affected sibpairs: effects of single
      locus approximations on estimates of the required sample size.
AB  - We investigated the power of the affected sibpair method for detecting a disease
      locus when the disease is inherited through two bi-allelic loci. The power was
      computed for all possible values of the gene frequencies and penetrances that
      lead to a given population prevalence and a given sibling relative risk. A method
      to generate rapidly all possible models that give a specific population
      prevalence and relative risk is provided. We applied it to the case of a two
      locus disease with a prevalence of 10% and a low sibling relative risk of 1.5.
      For this particular example, regardless of the true underlying model, a sample
      size (N = 450 for alpha = 0.05, N = 1,500 for alpha = 0.0001) may be determined
      such that one would expect enough power (0.80) to detect at least one of the two
      disease genes. In addition to the general case, we examined a special class of
      models in which the marginal penetrances at each locus are either recessive or
      dominant. In this instance, the gene frequencies were excellent predictors of the
      power afforded by a particular sample size. These methods have been implemented
      in a C program called SIBPOWER which is freely available from the first author.
      With this program, investigators can perform their own power calculations for any
      two-locus model of their choice thus avoiding the need to use single-locus
      approximations that may grossly underestimate the necessary sample size.

PMID- 9271712
TI  - Prevalence of factor V Leiden mutation in various populations.
AB  - Resistance to activated protein C (APC) is the most common inherited risk factor
      for venous thrombosis. Most cases of APC resistance are caused by the point
      mutation nt 1691 G-A in factor V gene, referred to as factor V Leiden mutation.
      As initially shown in a Dutch population, this mutation has a carrier rate of
      2.9%, the most frequent genetic disposition for thrombophilia and deep venous
      thrombosis. By large-scale epidemiological studies we have determined the
      prevalence of factor V Leiden mutation in populations from Poland (200),
      Argentina (215), Venezuela (126), Costa Rica (196), and India (150). The
      prevalences have been estimated for Poland (Warsaw) 5.0%, Argentina (Buenos
      Aires) 5.1%, Venezuela (Valencia) 1.6%, Costa Rica (San Jose) 2.0%, and India
      (Punjab) 1.3%. Based on worldwide distribution, it can be hypothesized that the
      factor V Leiden mutation has originated and accumulated in central European
      Caucasians and spread over the world by migration.

PMID- 9271713
TI  - Synergistic effect of two HLA heterodimers in the susceptibility to celiac
      disease in Tunisia.
AB  - The DR and DQ HLA genotypes of 94 Tunisian children affected with celiac disease
      are analyzed so that we can gain a better understanding of the HLA component of
      this disease. All of them carry at least one of two specific heterodimers: a DQ
      heterodimer, encoded by DQA1*0501, DQB1*0201 and/or a DR heterodimer, encoded by
      the nonpolymorphic gene DRA and the DRB4 gene. Quantifying the relative
      penetrances of all susceptible genotypes gives evidence for a synergistic effect
      of these two heterodimers and for a dose effect of the alleles encoding the beta
      chains of these two heterodimers. The DR3DR7 individuals have the greatest risk.
      They present the two kinds of heterodimers and carry two DQB1*0201 alleles.
      Celiac disease is the first HLA-associated disease for which the at-risk
      genotypes are so well delineated.

PMID- 9271714
TI  - Analyzing sibship correlations in birth weight using large sibships from Norway.
AB  - Data from the Medical Birth Registry of Norway were used to estimate sibship
      correlations in large sibships (each with > or = 5 infants among singleton live
      births surviving the first year of life), while adjusting for covariates such as
      infant gender, gestational age, maternal age, parity, and time since last
      pregnancy. This sample of 12,356 full sibs in 2,462 sibships born in Norway
      between 1968 and 1989 was selected to maximize the information on parity, and a
      robust approach to estimating both regression coefficients and the sibship
      correlation using generalized estimating equations (GEE) was employed. In
      concordance with previous studies, these data showed a high overall correlation
      in birth weight among full sibs (0.48 +/- 0.01), but this sibship correlation was
      influenced by parity. In particular, the correlation between the firstborn infant
      and a subsequent infant was slightly lower than between two subsequent sibs (0.44
      +/- 0.01 vs. 0.50 +/- 0.01, respectively). The effect of time between pregnancies
      was statistically significant, but its predicted impact was modest over the
      period in which most of these large families were completed. While these data
      cannot discriminate whether factors influencing birth weight are maternal or
      fetal in nature, this analysis does illustrate how robust statistical models can
      be used to estimate sibship correlations while adjusting for covariates in family
      studies.

PMID- 9271715
TI  - Evidence against genetic anticipation in familial colorectal cancer.
AB  - Anecdotal reports of hereditary colorectal cancer suggest that genetic
      anticipation (earlier appearance in successive generations) occurs, but
      ascertainment bias and cohort effects confound this interpretation. Using
      approaches that correct for such biases, we examined the age at diagnosis of
      colorectal cancer from family history questionnaires completed by subjects in the
      Johns Hopkins Hereditary Colorectal Cancer Registry; 475 parent-offspring pairs
      in 308 pedigrees were studied. We observed the expected cohort effect among
      offspring, in that the mean ages at diagnosis of those born before 1921, between
      1921 and 1930, and after 1930 were 63 +/- 13 (SD), 57 +/- 10, and 42 +/- 10
      years, respectively, while their parents' mean ages were 65 +/- 14, 66 +/- 14,
      and 58 +/- 15 years, respectively. In the cohort born before 1921, in which
      observation periods for both parents and offspring were comparable, there was no
      difference in age at diagnosis by pairwise comparison or life table analysis (P =
      0.15 and 0.23, respectively; r = 0.32). Subgroup analysis of 67 pairs from 38
      families that met the International Collaborative Group (ICG) criteria for
      hereditary nonpolyposis colorectal cancer (HNPCC) and of 14 pairs from 7 families
      with known germline mutations of DNA mismatch repair genes also showed no
      significant differences (mean age at diagnosis: 56 +/- 14 years for parents and
      57 +/- 16 years for offspring from ICG families, and 45 +/- 10 years for parents
      and 44 +/- 12 years for offspring in families with known mutations). We also
      found no evidence for effect of parental gender on age at diagnosis in offspring
      of either gender, nor a secular trend toward younger onset colorectal cancer in
      this sample. In conclusion, there is no evidence for genetic anticipation or
      genomic imprinting of age at diagnosis in this sample of colorectal cancer
      families. Apparent anticipation appears to reflect a birth cohort bias of
      ascertainment.

PMID- 9271717
TI  - Letting the deaf be deaf. Reconsidering the use of cochlear implants in
      prelingually deaf children.
AB  - In theory, cochlear implants hold out the possibility of enabling profoundly
      prelingually deaf children to hear. For these children's parents, who are usually
      hearing, this possibility is a great relief. Yet the decision to have this
      prosthetic device implanted ought not to be viewed as an easy or obvious one.
      Implant efficacy is modest and the burdens associated with them can be great.
      Moreover, the decision to forgo cochlear implantation for one's child, far from
      condemning her to a world of meaningless silence, opens the child up to
      membership in the Deaf community, which has a rich history, language, and value
      system of its own.

PMID- 9271716
TI  - The ethics of genetic research on sexual orientation.
AB  - Research into the genetic component of some complex behaviors often causes
      controversy, depending on the social meaning and significance of the behavior
      under study. Research into sexual orientation-simplistically referred to as "gay
      gene" research-is an example of research that provokes intense controversy. This
      research is worrisome for many reasons, including the fact that it has been used
      to harm lesbians and gay men. Many homosexual people have been forced to undergo
      "treatments" to change their sexual orientation. Other chose to undergo them to
      escape discrimination and social disapprobation. But there are other reasons to
      worry about such research. The very motivation for seeking an "origin" of
      homosexuality reveals homophobia. Moreover, such research may lead to prenatal
      tests that claim to predict for homosexuality. For homosexual people who live in
      countries with no legal protections these dangers are particularly serious.

PMID- 9271718
TI  - Testing testing.

PMID- 9271719
TI  - Provoking nonepileptic seizures: the ethics of deceptive diagnostic testing.
AB  - The use of deception in medical care is highly suspect in this country. Yet there
      is one condition for which deception is often used as a diagnostic tool.
      Nonepileptic seizures, a psychiatric condition in which emotional or
      psychological conflicts manifest themselves unconsciously through bodily
      symptoms, are currently diagnosed by a procedure called "provocative saline
      infusion." The test is fundamentally deceptive, requiring the physician to
      intentionally and directly lie to the patient, causing the patient to believe
      that the administered solution caused his seizures. Without such deception, the
      test might be useless.

PMID- 9271720
TI  - Food biotechnology's challenge to cultural integrity and individual consent.
AB  - Consumer response to genetically altered foods has been mixed in the United
      States. While transgenic crops have entered the food supply with little comment,
      other foods, such as the bioengineered tomato, have caused considerable
      controversy. Objections to genetically engineered food are varied, ranging from
      the religious to the aesthetic. One need not endorse these concerns to conclude
      that food biotechnology violates procedural protections of consumer sovereignty
      and religious liberty. Consumer sovereignty, a principle especially valued in
      this country, requires that information be made available so each individual or
      group may make food choices based on their own values. And as yet, there is no
      policy provision for informing consumers about the degree to which food has been
      genetically engineered.

PMID- 9271721
TI  - Bioethics on the Internet.

PMID- 9271722
TI  - A modified thoracotomy for minimally invasive coronary artery bypass grafting.
AB  - The optimal technique of minimally invasive coronary artery revascularization
      using the in situ internal thoracic artery (ITA), without extracorporeal
      circulation, is yet to be defined. To obtain adequate exposure for both ITA
      harvest and left anterior descending coronary artery anastomosis, an anterior
      chest wall defect is created which can be difficult to reconstruct. Based on the
      vascular anatomy of the acromiothoracic axis and three described osteocutaneous
      composite tissue flaps, we present a novel dissection that not only improves
      exposure, but also preserves chest wall integrity.

PMID- 9271723
TI  - The use of transesophageal echocardiography to guide sternal division for cardiac
      operations via mini-sternotomy.
AB  - Cardiac surgery utilizing the mini-sternotomy technique offers many advantages,
      including lessened pain and hospitalization. Mid-line upper sternotomy (or mini
      sternotomy) can provide adequate exposure of the ascending aorta, the aortic
      root, the right atrial appendage and the dome of the left atrium. Inherent in
      providing adequate exposure is the level at which the sternum is "T'd" off. The
      lower aspect of the sternotomy is "T'd" off at the second, third, or fourth
      intercostal space depending on the patient's anatomy. We describe a technique
      that uses transesophageal echocardiography to determine the precise location for
      "T'ing" off the sternotomy, rather than approximating the sternotomy site by
      physical exam and chest radiograph. This technique will reliably delineate the
      sternotomy site, irrespective of a patient's body size and habitus.

PMID- 9271724
TI  - Pleural drainage after repair of tetralogy of Fallot.
AB  - Prolonged pleural effusion after congenital heart surgery results in extended
      hospitalization. Pleural drainage was evaluated in 39 consecutive patients
      undergoing repair of tetralogy of Fallot, to identify risk factors for persistent
      pleural effusion. Duration and amount of drainage was examined by the Kaplan
      Meier method and risk factors were evaluated by univariable and multivariable
      analyses. Median time of pleural drainage was 6.1 days, range 3 to 42 days.
      Duration of pleural drainage correlated with length of hospital stay (p <
      0.0001). Postrepair right atrial pressure (p = 0.018) and preoperative hemoglobin
      (p = 0.035) were risk factors for persistent drainage. The presence of a previous
      right thoracotomy reduced drainage duration (p = 0.034). Prolonged mechanical
      ventilation increased the average daily volume of effusion (p < 0.0001). In
      conclusion, prolonged pleural effusion is an important morbidity factor after
      repair of tetralogy of Fallot. Bilateral chest tube insertion is indicated in
      patients with high preoperative hemoglobin and elevated postrepair right atrial
      pressure. Right thoracotomy is the preferred surgical approach when a preliminary
      palliative shunt is required.

PMID- 9271725
TI  - Surgical resection of right coronary artery stenoses.
AB  - A right coronary artery stenosis was resected in eight patients during
      multivessel operations. The artery was reconstructed by end-to-end anastomosis,
      restoring a normal antegrade pathway. All patients recovered uneventfully and
      remain asymptomatic at follow-up.

PMID- 9271726
TI  - Endoaneurysmal repair of a congenital right coronary sinus aneurysm.
AB  - An 82-year-old woman complained of lightheadedness, dizziness, syncope,
      palpitations, and chest pains of 2 years' duration. Chest X-ray demonstrated
      cardiomegaly, while transesophageal echocardiography (TEE) disclosed an aneurysm
      of the right coronary sinus (RCS), 6 x 6 cm in diameter, filled with clots and
      obstructing the right ventricular (RV) outflow tract. A total cardiopulmonary
      bypass was instituted with hypothermia to 28 degrees C esophageal temperature.
      After removing the clots, we applied an endoaneurysmal repair with a synthetic
      patch to the entry of the aneurysm and closed the aneurysm itself. We recommend
      our approach of an endoaneurysmal repair for similar aneurysms of the coronary
      sinus of Valsalva.

PMID- 9271727
TI  - Allograft conduit wall calcification in a model of chronic arterial graft
      rejection.
AB  - Early allograft vascular wall degeneration has emerged as a major important
      complication in young patients. To explain this mechanism, we reviewed studies on
      explants of allograft valved conduits implanted heterotopically into the
      infrarenal aorta in inbred rats (LEW; RT1I and CAP-RT1C). The following strain
      combinations (isografts and allografts) were used: syngeneic, LEW- > LEW,
      strongly allogeneic, and CAP > LEW (RT1- and non-RT1-incompatible). Second-set
      skin grafting was performed 3 weeks after the heterotrophic implant to test for
      immunogenicity and presensitization. The animals (LEW) were sacrificed serially
      on days 20, 30, 50, and 100 for immunofluorescence and SEM studies. Endothelial
      disruption was observed on day 30, while valve leaflets appeared normal. Humoral
      allograft rejection was demonstrated and associated with production of antibodies
      (IgG) against the endothelial cells and around the smooth muscle cells, and in
      areas of smooth cell necrosis, through 100 days. Neointimal repopulation by host
      cells and migrated smooth muscle cells was also observed in both viable and
      allovital grafts. Allovital grafts demonstrated more disorganized collagen and
      elastic fibers, as well as calcific degeneration in the media and neointima on
      day 50; the viable conduits showed such structural changes on day 100. In
      conclusion, vascular walls of allovital conduits calcified earlier than the
      viable conduits without discernible calcification of the valves. There is
      therefore evidence to prove causative relationships between cellular viability,
      immune response, and fibroproliferative calcific degeneration in allograft
      vascular conduits.

PMID- 9271728
TI  - Risk of left ventricular assist device as a bridge to heart transplant following
      postinfarction ventricular septal rupture.
AB  - Heart transplantation is an effective treatment for end-stage heart failure.
      However, due to the persistent shortage of donor hearts, many patients die
      awaiting a transplant. Implantable left ventricular assist devices are now
      available as a reliable bridge to cardiac transplantation. This report presents a
      patient with terminal heart failure as a result of a post-myocardial infarction
      ventricular septal rupture (VSR), who underwent a successful placement of the
      HeartMate left ventricular assist device (LVAD) and velour patch closure of an
      apical VSR. Despite this therapy, the patient expired after developing a second
      VSR, which created a high-flow right-to-left shunt and caused hypoxic
      irreversible brain injury. We suggest that use of a left ventricular assist
      device as a bridge to transplantation be approached with extreme caution in a
      patient with a postinfarction ventricular septal rupture.

PMID- 9271729
TI  - Coronary artery bypass grafting in patients with human immunodeficiency virus.
AB  - The role of surgery in the natural history of HIV disease is in evolution. A
      review was conducted of 2980 CABG operations taking place between January 1992
      and January 1996 at St. Vincents Hospital; four of these patients were known to
      be HIV-positive prior to the operation. Preoperative work-up, operative course,
      and postoperative events were largely unremarkable. Only 1 of the 4 patients
      required rehospitalization within 30 days. Follow-up averaged 28 months (range 7
      49 months). Three of four patients were in NYHA Class II or better at follow-up.
      Other reviews of CABG performed on HIV+ patients also indicate that, although CPB
      can be linked with immune suppression, there is no conclusive evidence of the
      acceleration of HIV into AIDS associated with CPB. In conclusion, due to the lack
      of controlled trials and large patient reviews, no firm recommendations about the
      effect of CPB on immunocompromized patients can be generated.

PMID- 9271730
TI  - Mitral annular flexibility.
AB  - An analysis of three-dimensional movement of the mitral valve annulus (MVA) may
      address the question of geometrical change after mitral valve repair to preserve
      mitral annular function. Conventionally, annular contraction has been studied for
      this purpose. We investigated this geometrical change occurring in the anterior
      half of the MVA and discuss its clinical significance. Three-dimensional images
      of the MVA during systole were reconstructed from magnetic resonance images of
      eight normal subjects. The posterior half of the MVA exhibited translational
      motion. We assume that this portion, exhibiting translational motion as well as
      contraction, purely follows the motion of the left ventricular contraction.
      Compensating for the discrepancy between the motion of the aortic root and that
      of the posterior half of the MVA, the anterior half exhibited a flexible change
      in shape during systole, thus maintaining a sufficient left ventricular outflow
      tract (LVOT). The increase in the extent of displacement of the anterior MVA from
      the posterior half of the MVA during systole, which was 3.6 +/- 1.0 mm (mean +/-
      SD), indicates the annular flexibility. The preservation of annular flexibility
      may prevent LVOT obstruction. Further geometrical analysis of patients after
      mitral repair will clarify annular function as presented in this article.

PMID- 9271732
TI  - Inverted T-shaped biatral incision for large left atrial myxoma.
AB  - Various surgical approaches for a left atrial myxoma have been developed to
      provide optimal exposure and to allow radical excision of the tumor. However,
      when a myxoma occupies most of the left atrium, it is difficult to remove the
      friable tumor without fragmentation. The inverted T-shaped biatrial incision is a
      modified transseptal approach to expose the mitral valve. Using this approach, we
      can extirpate even a huge tumor without fragmentation. A horizontal incision of
      the left atrium is made, followed by a vertical incision into the right atrium. A
      careful assessment is made as to whether or not this biatral approach is
      sufficient to remove the large left atrial myxoma. If exposure is considered
      inadequate, the interatrial groove is divided. The incision is continued distant
      from the pedicle, if possible, more than 5 mm away. The tumor is excised,
      including tissue around the base of the tumor, with wide margins.

PMID- 9271731
TI  - Microfibrillar collagen (Avitene) and antibiotic-containing fibrin-glue after
      median sternotomy.
AB  - A technique to control bleeding before closure of median sternotomy after cardiac
      procedures is described. This technique is useful in patients when conventional
      methods of hemostasis are ineffective because of hypocoaguability, sternal
      fracture, or friable sternum.

PMID- 9271733
TI  - Bentall operation for a child with Marfan syndrome: a case report.
AB  - Children with Marfan syndrome rarely undergo surgery for annuloaortic ectasia and
      aortic regurgitation in the first decade. A 7-year-old girl presented with
      congestive heart failure due to severe aortic regurgitation associated with
      annuloaortic ectasia (6 cm). She also had funnel chest. She underwent a Bentall
      operation and sternal turn-over with a satisfactory result. Since the aortic
      valve cusps had rolled edges, the aortic valve was not spared. Histology of the
      aortic valve cusps showed myxoid degeneration and fragmentation of elastic
      fibers.

PMID- 9271734
TI  - Effects of carnitine on preconditioned latissimus dorsi muscle at different burst
      frequencies.
AB  - Exercise and electrical stimulation may result in a decrease in carnitine levels
      associated with preconditioned latissimus dorsi muscles. Therefore, the effects
      of exogenous carnitine were studied in a model of latissimus dorsi muscle
      contraction. Twelve dogs were studied. Under anesthesia, the latissimus dorsi was
      placed around an implantable mock circulation system. The muscle was made fatigue
      resistant with the aid of chronic low-frequency electrical stimulation. Six
      animals received carnitine 0.15 mmol/kg; the other six served as control. The
      muscles were stimulated with 20, 43, and 85 Hz pulse training. During the 90
      minute stimulation period, the pressure that developed in the mock circulation
      was measured at 15 minute intervals. The changes in ATP and lactate levels were
      measured every 30 minutes. Stimulations at 20 and 43 Hz did not result in any
      change in pressure or metabolic data over the course of 90 minutes of
      stimulation. When the 85 Hz burst was applied, ATP levels decreased, while
      lactate levels increased, with an associated drop in pressure in the control
      group. ATP and lactate levels were, respectively, 13.8 +/- 1.4 mumol/g and 15.0
      +/- 4.0 mumol/g in the carnitine group and 10.3 +/- 1.1 mumol/g and 23.0 +/- 3.0
      mumol/g in the control group at the end of 90 minutes (p < 0.06). The pressure at
      the same time interval was 74 +/- 4 mmHg in the control group, and 85 +/- 3 mmHg
      in the carnitine group (p < 0.05). In this study, we demonstrated that carnitine
      administration enhances muscle performance in terms of metabolic and pressure
      changes during high-frequency electrical stimulation at 85 Hz.

PMID- 9271735
TI  - Chest wall infarction following bilateral internal mammary to coronary arterial
      bypass in a patient with a thoracoabdominal aneurysm.
AB  - A 69-year-old man with severe peripheral vascular disease and a known
      thoracoabdominal aortic aneurysm underwent bilateral internal mammary artery
      (BIMA) to coronary artery bypass grafting and aortic hemiarch replacement. He
      immediately thereafter developed massive chest wall ischemia and infarction with
      a severe metabolic acidosis, and subsequently died. Chest wall infarction
      following BIMA harvesting has not been previously described. Cautious use of
      internal mammary arterial grafting may be in order in the severe vasculopath with
      significant thrombo-occlusive thoracoabdominal aortic disease.

PMID- 9271737
TI  - Aortic root surgery in Marfan syndrome: current practice and evolving techniques.
AB  - BACKGROUND: Our current approach to aortic root disease in patients with Marfan
      syndrome is replacement with a composite valve graft, a technique with
      established excellent early and long-term results. The purpose of this report is
      to retrospectively review our results with aortic root replacement in Marfan
      patients and to discuss the status of several alternative techniques, chiefly
      aimed at eliminating the need for a mechanical valve, that are currently under
      investigation. PATIENTS AND METHODS: In patients with Marfan syndrome, we perform
      aortic root replacement for all ascending aortic dissections and significant
      annuloaortic ectasia or aortic valvular insufficiency. We reserve concomitant
      mitral valve surgery for those patients with clinically significant
      regurgitation. From February 1991 through July 1996, 45 patients with Marfan
      syndrome underwent aortic root replacement; 44 of the patients (97.8%) had
      composite valve grafts placed. Thirteen patients (28.9%) required concomitant
      graft replacement of the transverse aortic arch and four patients (8.9%)
      underwent concurrent mitral valve replacement. RESULTS: There were no
      intraoperative deaths, two early deaths (4.4%), and no postoperative strokes. No
      patient has developed evidence of an anastomotic pseudoaneurysm nor graft
      infection during follow-up. CONCLUSIONS: Composite valve graft replacement of the
      aortic root carries low morbidity and mortality, produces excellent long-term
      results, and currently remains the treatment of choice for proximal dissection or
      significant annulo-aortic ectasia in patients with Marfan syndrome. Alternative
      techniques are evolving; however, further long-term data demonstrating durability
      that compares favorably to established techniques will be required before
      recommending their routine use.

PMID- 9271736
TI  - Marfan syndrome--current medical and genetic knowledge: how to treat and when.
AB  - Marfan syndrome (MFS), first described 100 years ago, remains a clinical
      diagnosis. Two out of 3 major systems (ocular, cardiac, skeletal) must be
      classically affected, to avoid overdiagnosis. Diagnosis may be confirmed by
      linkage to the dominantly inherited gene MFS-1 on 15q21, or by discovering the
      family mutation. Either technique may be used for prenatal diagnosis. Modern
      medical and surgical management is prolonging life, by on average, 13 years, with
      postoperative 20 year survival rate 65%. Beta-blocker therapy slows aortic root
      dilatation, and elective surgery is offered at ascending aorta diameter > or = 5
      cm. Known associations with early death include new mutation, family history of
      dissection < 5 cm, male sex, and emergency surgery where the death rate is 5
      times higher than in elective surgery. Pregnancy bears a 1% risk of fatal
      complication, and this risk rises with increasing aortic root diameter. Caesarean
      section at 38 weeks gestation should be offered if aortic root diameter is
      greater than 4.5 cm. Gene mapping reveals almost every mutation to be unique,
      interfering with multimerization of fibrillin monomers, or interactions with
      other connective tissue elements. Neonatal MFS is caused by mutations in exons 24
      32, in calcium-binding EGF-like sequences. Mutations affecting cysteines or amino
      acids critical for calcium binding in other EGF-like domains, or deletions of
      complete EGF-like domains, generally lead to classical MFS phenotypes, as do
      mutations in TGF receptor-like domains. Heterogeneity has been reported with a
      second locus (MFS-2) on chromosome 3 in one French pedigree.

PMID- 9271738
TI  - The Bentall procedure in patients with Marfan's syndrome.
AB  - From 1985 to 1996, 18 patients with Marfan's syndrome underwent the Bentall
      procedure at Mount Sinai Hospital. They are compared with 38 patients aged < 40
      without Marfan's syndrome who also underwent composite valve-graft replacement of
      the ascending aorta. The mean age of the non-Marfan group was 33 while that of
      the Marfan group was 29. Nearly three-quarters of each group were male. Aortic
      dissection was present in 33% of the Marfan group but only in 18% of the other
      group. Seventy-eight percent of the Marfan patients and 89% of the non-Marfan
      patients had aortic regurgitation. Twenty-one percent of the patients in the
      control group nevertheless had gross aortic pathology suggestive of Marfan's
      syndrome and may have had variants of the syndrome; 26% of the non-Marfan group
      had a bicuspid aortic valve. A modification of the Bentall procedure with
      implantation of coronary artery buttons was performed in the majority of the
      patients in both groups. Three patients, all in the group with Marfan's syndrome,
      required a concomitant mitral valve procedure. There was one death in each group.
      Two non-Marfan patients required reoperation; neither had dissection. Four
      patients with Marfan's syndrome underwent reoperation for distal disease in the
      aorta; they comprised one third of the Marfan patients who had aortic dissection.
      Three late complications occurred in the group with Marfan's syndrome:
      progressive cardiomyopathy; myocardial infarction; and late tamponade. There were
      also two late sudden deaths in the group with Marfan's syndrome, which may have
      been the consequence of aortic rupture. No difference in immediate operative
      mortality following the Bentall procedure was noted between patients with and
      without Marfan's syndrome, but young patients without Marfan's syndrome seem to
      have better event-free and long-term survival. In patients with Marfan's
      syndrome, the presence of acute dissection makes reoperation more likely, and
      sudden death from rupture still occurs despite careful postoperative
      surveillance. A higher incidence of severe mitral valve disease was found among
      young patients with Marfan syndrome than in controls.

PMID- 9271739
TI  - Current practice in Marfan's aortic root surgery: reconstruction with aortic
      valve preservation or replacement? What to do with the mitral valve?
AB  - BACKGROUND: Until recently the surgical treatment of aneurysms of the aortic root
      in patients with the Marfan syndrome consisted of composite replacement of the
      aortic valve and ascending aorta. At the present, almost one-half of these
      patients can have reconstruction of the aortic root with preservation of the
      aortic valve. The mitral valve can also be frequently preserved. PATIENTS AND
      METHODS: From 1988 to 1996, 46 patients with the Marfan syndrome and aortic root
      aneurysm underwent cardiac surgery; the aortic valve was preserved in 23 and
      replaced in 26. The mitral valve was repaired in 3 patients who had aortic valve
      sparing operations, and it was repaired in 3 and replaced in 3 who had aortic
      valve replacement. Both groups of patients had similar clinical profile. RESULTS:
      There were 2 operative deaths among patients who had aortic valve replacement but
      neither one was valve-related. One patient who had aortic valve-sparing operation
      needed aortic valve replacement 2 years postoperatively. There were no other
      valve-related complications in this group. The actuarial survival was 100% at 5
      years for this group. Four patients needed reoperations for valve-related
      complications in the group who had composite replacement of the aortic valve and
      ascending aorta. The actuarial survival was 88% +/- 4% at 5 years in this group.
      CONCLUSIONS: Although the number of patients in each group is small and the
      follow-up relatively short, aortic valve-sparing operations have given gratifying
      results and may prove superior to valve replacement in patients with the Marfan
      syndrome.

PMID- 9271740
TI  - Valve conserving operation for aortic regurgitation.

PMID- 9271741
TI  - Current practice in Marfan's syndrome and annulo-aortic ectasia: aortic root
      replacement with a composite graft over a twenty-year period.
AB  - BACKGROUND: From October 1973 to December 1995, 251 patients (204 male, 47
      female) aged from 10 to 75 years (mean: 46.6 +/- 15) underwent an ascending
      aortic replacement with a composite graft for: dystrophic aneurysm (AN), 168
      cases (66.9%); chronic dissection (CD), 36 cases (14%); and type A acute
      dissection (AD), 48 cases (19.1%). Fifty-one patients (20.3%) suffered from
      Marfan's disease (25 AN, 17 AD, 9 CD). Thirty-seven patients (14.7%) had
      undergone a previous cardiac or aortic operation. The ascending aortic
      replacement was extended to the transverse arch in 31 patients (12.3%). A
      mechanical valve was used in 233 patients (92.8%). The classic "Bentall"
      technique was used in 87 patients (34.6%), the "button" technique in 121 patients
      (48.2%), the "Cabrol" technique in 26 patients (10.3%) and a "mixed" technique in
      17 patients (6.2%). RESULTS: The hospital mortality accounts for 7.2% (18 out of
      251) (AN: 4 out of 68, 2.3%, CD: 4 out of 36, 11.1%, AD: 9 out of 48, 18.7%).
      When emergencies are considered, the hospital mortality is 12 out of 54 (22.2%)
      versus 6 out of 197 (3%) in elective procedures. The predictors of hospital death
      were emergency, AD (p < 0.03) and arch replacement (p < 0.02). Mean follow up is
      38 +/- 15 months (4-262). The overall long term survival rate is (Kaplan Meier):
      92 +/- 6% at one year, 77.9% +/- 9% at 5 years, 67.7 +/- 12% at 10 years, and
      61.3 +/- 15% at 12 years. The 10-year survival rate is significantly higher in
      patients with AN (93 +/- 6%) than in patients with AD (61.6 +/- 17%) (p < 0.01).
      The late survival rate is also significantly higher after the "button" (93.8 +/-
      5%) or Bentall's reimplantation (88.7 +/- 6%, 83.8 +/- 9%, and 76.6 +/- 12%) than
      after the "Cabrol" procedure (80 +/- 18%, 63 +/- 21% and 58 +/- 35%) at 1, 5, and
      8 years, respectively. CONCLUSION: Ascending aortic replacement with a composite
      graft is a safe procedure, especially when performed electively in patients with
      dystrophic aneurysm or Marfan's disease. The technique of coronary reimplantation
      has a significant influence of the long-term results, with the reimplantation of
      choice being the "button" technique. The "Cabrol" technique must be used when the
      "button" or the "Bentall" reimplantation is not feasible.

PMID- 9271742
TI  - Current status of thoracoabdominal aortic aneurysm repair in Marfan syndrome.
AB  - BACKGROUND: Patients with Marfan syndrome frequently develop aneurysms or
      dissections involving multiple segments of the aorta; graft replacement of
      multiple aortic segments prolongs survival. Indications for graft replacement of
      the thoracoabdominal aortic segment include impending rupture, ischemic
      complications from dissection, or an aortic diameter measuring 5.5 cm or more. We
      retrospectively reviewed our experience with 50 consecutive thoracoabdominal
      aortic aneurysm repairs in Marfan patients to evaluate the results of surgery
      using contemporary techniques. PATIENTS AND METHODS: From January 1986 through
      July 1996, 800 patients underwent graft replacement of thoracoabdominal aortic
      aneurysms. Fifty patients (6.3%) had Marfan syndrome. Aneurysms without
      dissection were present in nine (18%) of the Marfan patients. The remaining 41
      patients (82%) had chronic dissection. Both chronic dissection and Crawford
      extent II aneurysms were more prevalent in patients with Marfan syndrome than in
      non-Marfan patients. Extensive thoracoabdominal aortic aneurysm repairs (extents
      I and II) were performed in 72% of Marfan patients; atriodistal bypass was used
      in 22 patients (44%). RESULTS: The 30-day survival rate was 96%. Renal failure
      requiring hemodialysis occurred in three patients (6%). Two patients (4%) had
      postoperative lower extremity neurological deficits. No patient receiving
      atriodistal bypass developed paraplegia or paraparesis, versus two patients
      (7.1%) among the 28 who did not. CONCLUSION: Patients with Marfan syndrome have a
      high prevalence of extent II aneurysms and associated dissection. Using
      contemporary surgical techniques, Marfan patients can undergo thoracoabdominal
      aortic aneurysm repair with low mortality and morbidity, despite the extensive
      nature of their disease.

PMID- 9271743
TI  - Penetrating injuries to the thoracic great vessels.
AB  - Penetrating injuries to the thoracic great vessels have been diagnosed with
      increased frequency because of the escalating use of automatic weapons. The
      overall incidence is 5.3% of gunshot wounds and 2% of stab wounds to the chest.
      Most of these patients reach the hospital dead or in severe shock. The overall
      mortality of thoracic aortic injuries is higher than 90% and in subclavian
      vascular injuries higher than 65%. In the prehospital phase, the "scoop and run"
      policy offers the best chances of survival and no attempts should be made for any
      form of stabilization. Investigations should be reserved only for fairly stable
      patients. Angiography, color flow Doppler, and transesophageal echocardiography
      may be useful in selected cases. Patients in cardiac arrest or imminent cardiac
      arrest may benefit from an emergency room thoracotomy. The surgical approach to
      specific thoracic great vessels is described.

PMID- 9271744
TI  - Diagnosis and management of blunt great vessel trauma.
AB  - Traditionally, thoracic aortic rupture, suspected after blunt thoracic trauma, is
      characterized by a chest radiograph showing a widened mediastinum. The diagnostic
      machinery consecutively activated still depends heavily on the pressure as
      additional traumatic lesions. A patient with additional cranio-cerebral trauma
      would typically undergo contrast-enhanced computed tomography or magnetic
      resonance imaging of head, chest, and other regions. In a number of patients
      these analyses would confirm the presence of blood in the mediastinum without
      formal proof of an aortic disruption. This is because mediastinal hematomas may
      be caused not only by an aortic rupture, but also by numerous other blood sources
      including fractures of the spine and other macro- and microvascular lesions
      providing similar images. Therefore, aortic angiography became our preferred
      diagnostic tool to identify or rule out acute traumatic lesions of not only the
      aorta but with great vessels. However recently, a number of traumatic aortic
      transsections have been identified by transoesophageal echocardiography (TEE).
      TEE has the additional advantage of being a bed-side procedure providing
      additional information about cardiac function. The latter analysis allows for
      identification and quantification of cardiac contusions, post-traumatic
      myocardial infarctions, and valvar lesions which are of prime importance to
      develop an adequate surgical strategy and to assess the risk of the numerous
      emergency procedures required in patients with polytrauma. The standard approach
      for repair of isthmic aortic rupture is through a lateral thoracotomy. Distal and
      proximal control of the aorta can be achieved in a substantial number of cases
      before complete aortic rupture occurs and a higher proportion of direct suture
      repair can be achieved under such circumstances. Most proximal descending aortic
      procedures are performed without cardiopulmonary bypass (clamp and go) but
      paraplegia may occur before, during, or after the procedure. Ascending aortic
      lesions and disruption of the aortic arch, the supra-aortic vessels, the main
      pulmonary arteries, the great veins as well as cardiac lesions are best
      approached through a sternotomy, which may have to be extended. Cardiopulmonary
      bypass allowing for deep hypothermia and circulatory arrest is often required and
      carries its own complications. It is not clear whether the increasing proportion
      of ascending aortic and cardiac lesions which are observed nowadays are due to a
      change in trauma mechanics (i.e., speed limits, seat belts, air-bags), an
      improvement of the diagnostic tools or both.

PMID- 9271745
TI  - How do we protect the brain? Antegrade selective cerebral perfusion with cold
      blood during aortic arch surgery.

PMID- 9271747
TI  - Safety and efficacy of aprotinin in profoundly hypothermic circulatory arrest.

PMID- 9271746
TI  - Hematological consequences of profound hypothermic circulatory arrest and aortic
      dissection.
AB  - The lower temperatures utilized during profound hypothermic circulatory arrest
      (PHCA) surgery may exacerbate the hypothermia associated platelet and clotting
      factor dysfunction observed in conventional cardiopulmonary bypass (CPB)
      procedures. Hypothermia has been shown to impair the activity of the enzymes
      involved in the platelet activation pathways and to reduce the enzymatic activity
      of clotting factors upon coagulation activation. The resulting retardation of the
      generation of fibrin/platelet clot compounded by the presence of heparin may
      contribute significantly to a bleeding tendency. Excessive fibrinolytic activity
      may disrupt surgical wound thrombi and exacerbate haemorrhage. There is good
      evidence that the fibrinolytic activity, mediated predominantly by tissue
      plasminogen activator (tPA), is a secondary response to thrombin generated by
      coagulation activation, which is ongoing during CPB despite full heparinization.
      The effects of hypothermia on the fibrinolytic response remain to be clarified
      and the extent to which the lower temperatures and blood stasis associated with
      PHCA moderate this response is unknown. Despite impairment of coagulation
      activation by hypothermia there appears to be a shift in the hemostatic balance
      towards thrombosis presumably as a consequence of endothelial cell injury by both
      hypothermia and stasis induced ischemia. There is evidence that widespread
      microvascular thrombus deposition may occur as a consequence of stasis in
      patients undergoing PHCA and that this might result in vascular occlusion and end
      organ damage. Although it is not uncommon to find laboratory evidence of
      disseminated intravascular coagulation (DIC) in patients presenting with aortic
      aneurysm rupture or dissection, the incidence of clinically overt DIC resulting
      in bleeding is low. The underlying hemostatic disturbance however may contribute
      to the surgery-associated bleeding diathesis.

PMID- 9271748
TI  - A case for aprotinin in patients having deep hypothermic circulatory arrest.

PMID- 9271749
TI  - Individual strategies of hemostasis for thoracic aortic surgery.
AB  - The problem of altered hemostasis remains a major challenge during thoracic
      aortic surgery. Bleeding is associated with a marked increase in morbidity and
      mortality. The hemostatic derangements are caused by multiple interrelated
      factors including interference with the vascular integrity, extensive surgical
      dissection, transient need for complete inhibition of the normal coagulation
      process, large blood products and fluid requirements, hemodilution, hypothermia,
      extensive ischemia and reperfusion, activation of systemic inflammatory
      responses, interference with fibrinolysis, and the use of extracorporeal
      circulation systems. Acquired coagulopathy must be specifically diagnosed and
      treated. Platelet deficiencies, both qualitative and quantitative, are the most
      predictable and consistent disturbance in the hemostatic function and the most
      common cause of intraoperative and postoperative bleeding. Precise surgical
      technique is essential to prevent blood loss. Topical agents should not be used
      for and cannot correct imperfections in surgical technique. Nonspecific
      measurements that are useful to decrease intraoperative blood loss include strict
      control of blood pressure and hemodynamic status, the induction of mild
      controlled hypotension, and the reversal of hypothermia. Rewarming may produce
      clear procoagulant effects by improving the efficacy of platelets and clotting
      factors. Platelet dysfunction can be reduced by several pharmacological
      interventions including acid aminocaproic, desmopressin and aprotinin; however,
      efficacy and safety are still being established. The most important factorS
      regarding safety in thoracic aortic surgery are a secure suture line and the
      experience of the surgical and anesthesiology teams.

PMID- 9271750
TI  - Hemostasis for aortic surgery.

PMID- 9271751
TI  - Hemostasis in aortic and cardiothoracic surgery.
AB  - Hemostasis abnormalities in cardiovascular and aortic surgery remain a major
      source of morbidity and mortality in patients undergoing such complex procedures.
      The need for frequent transfusions of red cell and other blood products increases
      risks and costs to patients and institutions providing patient care. Specifically
      in cardiovascular and aortic surgery, the nature of the surgery is, at best, semi
      elective, and careful preparation to preserve the hemostatic mechanisms of the
      body is essential. Contact of blood with the extracorporeal circuit induces a
      hemorrhagic diathesis through a variety of different mechanisms. Dilution of the
      patient's blood volume by the extracorporeal circuit prime causes depletion of
      platelets and coagulation factor levels. Aorto intimal disease initiates
      fibrinolysis by the release of tissue plasminogen activator. Due to the numerous
      etiologies of bleeding, a combination of blood conservation strategies is
      suggested. The ideal combination of interventions has yet to be determined and is
      currently dependent on patient variables, physician and institutional practices,
      and economic pressures.

PMID- 9271752
TI  - The management of bleeding following surgery requiring hypothermic circulatory
      arrest.
AB  - BACKGROUND: Hemostasis is a significant problem in aortic surgery requiring
      profoundly hypothermic techniques. Aprotinin, a serine protease inhibitor,
      reduces blood loss in high-risk coronary and valve surgery, but its use in
      profound hypothermia is controversial. METHODS: To evaluate the role of a
      modified protocol of aprotinin administration we have retrospectively reviewed
      our results in 73 procedures when hypothermic circulatory arrest was necessary.
      Thirty-seven (51%) were emergencies. Aprotinin was not administered until bypass
      had been recommenced after the period of circulatory arrest, and was then given
      as a bolus of 280 mg into the bypass machine followed by an intravenous infusion
      of 70 mg/hour. RESULTS: In this series the 30-day mortality was 12.3% (9/73), and
      the in-hospital mortality 13.7% (10/73). Mortality in the elective group was
      11.1% and 16.2% in the emergency group. The mean blood loss over the first 12
      hours after surgery was 542 mL; the mean transfusion requirement during surgery
      and this 12 hour period was 3.6 units of blood. Six patients (8.2%) developed
      transient renal dysfunction which did not require intervention. CONCLUSIONS: This
      data does not support the adverse effect of aprotinin upon early survival.
      Although early reports were of concern, the role of aprotinin as an adjunct to
      hemostasis requires further investigation.

PMID- 9271753
TI  - The proper use of glue: a 20-year experience with the GRF glue in acute aortic
      dissection.
AB  - BACKGROUND: In 1977, the use of Gelatine-Resorcine-Formaline (GRF) biological
      glue during surgery of acute Type A aortic dissection was proposed. The present
      study retrospectively analyzes the late results obtained with this adjunct in an
      experience extending over a twenty-year period of time. PATIENTS AND METHODS:
      From January 1977 to March 1996, 171 patients (124 males and 47 females) aged
      from 15-79 years (mean age: 53 +/- 14 years) underwent an emergency operation for
      type A aortic dissection in our institution. All patients suffered from acute
      type A dissection and 144 (84%) were operated on within 48 hours after the onset
      of symptoms. Twenty-six patients (15.2%) had Marfan's syndrome. The ascending
      aorta was replaced in all patients and the aortic stumps were reinforced with the
      GRF glue. In 39 patients (23%), the aortic valve was replaced either
      independently (5 cases, 3%) or by means of a composite graft (34 cases, 19.8%).
      Because of the location of the intimal tear, the aortic replacement was extended
      to the transverse arch in 58 patients (33.9%). RESULTS: Hospital mortality
      amounts to 21% (36 patients), 22.8% in patients with arch replacement and 21.1%
      in patients without arch replacement (n.s). One hundred thirty-five patients were
      discharged and surveyed from 2 months to 19 years postoperatively (cumulative
      follow-up: 856 patients/years. Mean follow-up: 79 +/- 66 months). During this
      period of time, 22 patients (16.1%) had to be reoperated on for a total of 28
      reoperations. Six of those (27.2%) died at reoperation. At univariate analysis,
      presence of Marfan's syndrome (p < 0.05) and absence of arch replacement (p <
      0.02) were determinant risk factors for reoperation. Emergency (p < 0.01) and
      thoracoabdominal replacement (p < 0.04) were determinant risk factors of death at
      reoperation. The acturial freedom from reoperation (Kaplan-Meier, CI: 95%) is:
      96.08% (90.9-98.2), 87.6% (79.8-92.7), 80.9% (70.8-86.1), 66.4% (51.1-78.9) at 1,
      5, 10, and 15 years respectively. A total of 36 patients (27.7%) died during
      follow-up. Presence of Marfan's syndrome (p < 0.01), reoperation (p < 0.02),
      stroke (p < 0.05), cardiac failure (p < 0.05) were determinant risk factors of
      late mortality. The actuarial late survival rate (K-M. C.I.: 95%), including
      hospital mortality, is: 71.5% (64.3-77.8), 66% (58.3-73), 56.4% (47.7-64.7),
      46.3% (36.4-56.5) at 1, 10 and 15 years. CONCLUSIONS: The GRF glue has proved to
      be extremely useful during emergency initial surgery for acute type A dissection,
      making the procedure much easier and safer. Through this operative improvement,
      the use of the GRF glue seems to have a beneficial influence on the late results
      which however, depend mainly on the patient's basic condition.

PMID- 9271754
TI  - The infected aorta.
AB  - BACKGROUND: Despite the improvements achieved in antibiotic therapy, severe
      aortic infection resulting in mycotic aneurysms is still a highly lethal disease
      and surgical management remains a challenging task. PATIENTS AND METHODS: A total
      of 43 patients with severe aortic infections were analyzed and separated in four
      groups: (1) Infections of the aortic root Ventriculo-aortic disconnection due to
      deep aortic infection (6 patients). Two patients were operated using homo
      composit grafts. Of the 6 patients total, one died early and two died late during
      a mean follow-up of 6 years. The two patients with homografts are still alive.
      (2) Infections of the ascending aorta and the aortic arch. In situ repair for
      mycotic aneurysmal lesions of the ascending aorta was performed in 6 patients
      using synthetic graft material in 4/6, biological material in 1/6 and direct
      suture in 1/6. Two patients had to be reoperated; one of them died early. There
      was no recurrent infection during a mean follow-up of 6 years. (3) Infections of
      the descending thoracic and thoraco-abdominal aorta in-situ repair for mycotic
      aneurysmal lesions of the descending and thoraco-abdominal aorta was performed in
      12 patients using homografts in five. Two patients died early and two other
      patients died late during a mean follow-up of 6 years. (4) Infections of the
      infrarenal abdominal aorta. In this series of 19 patients with mycotic infrarenal
      aortic aneurysms, in situ reconstruction was performed in 12 (5/12 with
      homografts) and extra-anatomic reconstruction (axillo-femoral bypass) was
      performed in 7. Hospital mortality was 5/19 patients and another 5/19 patients
      died during a mean follow-up of 6 years. One of the early deaths was due to
      aortic stump rupture. Two patients with axillo-femoral reconstructions were later
      converted to descending-thoracic-aortic-bifemoral bypasses. Five thromboses of
      axillo-femoral bypasses were observed in three of the seven patients with extra
      anatomic repairs. RESULTS: Infections of the aortic root, the ascending aorta and
      the aortic arch are approached with total cardio-pulmonary bypass, using
      cardioplegic myocardial protection and deep hypothermia with circulatory arrest
      if necessary. Proximal unloading and distal support using partial cardiopulmonary
      bypass is preferred for repair of infected descending and thoracoabdominal aortic
      lesions, whereas no such adjuncts are required for repair of infected infrarenal
      aortic lesions. CONCLUSIONS: The anatomical location of the aortic infection and
      the availability of homologous graft material are the main factors determining
      the surgical strategy.

PMID- 9271755
TI  - Surgical management of aortic root abscess.
AB  - BACKGROUND: The mortality and morbidity associated with surgery for aortic root
      abscess is reportedly high. This is a review of our experience with radical
      resection of the abscess and reconstruction of the left ventricular outflow tract
      with pericardium. METHODS: Sixty-three consecutive patients with aortic root
      abscess were operated on since 1980. Their mean age was 47 years, range 16 to 75;
      53 patients were men. Thirty-one patients had native and 32 had prosthetic valve
      endocarditis; of these 32, 13 had previous composite replacement of the aortic
      valve and ascending aorta. The most common offending microorganisms were
      staphylococci, which were cultured in 31 patients. The abscess was confined to
      the aortic annulus in 22 patients and had extended into surrounding structures in
      41. The abscess involved the mitral valve in 13, the tricuspid valve in 2, and
      the pulmonary valve in 1. Radical resection of the abscess and reconstruction of
      the left ventricular outflow tract and other valve annull was accomplished with
      autologous or glutaraldehyde-fixed bovine pericardium. Aortic valve homograft was
      used in only three patients; prosthetic heart valves in 60. RESULTS: There were
      eight deaths; 26 patients experienced one or more non-fatal perioperative
      complication. Patients were followed up for a mean of 58 +/- 39 months. There
      were ten late deaths; the actuarial survival at 10 years was 55% +/- 10%. Nine
      patients developed late recurrent endocarditis 10 to 108 months postoperatively.
      The freedom from recurrent endocarditis at 10 years was 75% +/- 8%. CONCLUSIONS:
      Radical resection of aortic root abscess and reconstruction of the left
      ventricular outflow tract with pericardium is an effective method to eradicate
      the infection. These patients appear to have a relatively high risk of recurrent
      endocarditis.

PMID- 9271756
TI  - The natural history of thoracic aortic aneurysm disease: an overview.
AB  - Relatively little is known of the natural history of thoracic aortic aneurysms
      (TAA). The limited data available suggests that survival is at best equivalent to
      that observed for abdominal aortic aneurysm (AAA), and probably significantly
      worse. Patients with an AAA > 6 cm diameter have a 5-year survival of 10%, with a
      cumulative risk of rupture over 10 years of 43%. Rupture is also responsible for
      death in 25% of patients with 4-7 cm AAA. Natural history studies of TAA report a
      1- and 5-year survival of 39%-52% and 13%-19%, respectively, but many studies
      include data on acute type A dissection. Although most mortality in patients with
      TAA is related to aneurysm rupture, data on the relationship between aneurysm
      size and rupture risk remains scarce. TAA is a highly lethal condition warranting
      consideration of elective, prophylactic surgical repair. However, the timing of
      surgery is often a difficult clinical decision, particularly in asymptomatic
      patients or those with comorbid conditions. Surgery for TAA carries a significant
      mortality and potentially permanently crippling morbidity. A recommendation of
      surgery represents a balance, weighing estimates of TAA natural history and
      rupture risk against operative mortality and complication rate, while carefully
      considering the impact of important comorbid conditions, e.g., ischemic heart
      disease, obstructive pulmonary disease, and renal dysfunction. When to intervene
      is a critical question facing cardiovascular surgeons and is based upon an
      assessment of the risk of rupture. This risk is related to the site, aetiology,
      size, and expansion rate of the aneurysm.

PMID- 9271757
TI  - Natural history of aneurysms of the descending and thoracoabdominal aorta.

PMID- 9271758
TI  - Natural history of descending and thoracoabdominal aortic aneurysms.
AB  - Data on the natural history of descending and thoracoabdominal aneurysms are
      limited to a few studies. They demonstrated that, independent from the different
      mechanisms of injury and degeneration affecting the structural integrity of the
      aortic wall, the biologic fate of all aneurysms is progressive enlargement and
      rupture. Laminated thrombus and calcification do not prevent this process. The
      natural history is markedly influenced by size, location, symptoms, and etiology
      of thoracic aneurysms. They may develop symptoms related to mechanical
      compression of adjacent structures, but more frequently they are asymptomatic
      until rupture occurs. Usually, aortic rupture causes death by exsanguination and
      shock before bleeding can be controlled. Occasionally, rupture can be contained
      by the parietal pleura or occur towards the mediastinum, esophagus, pulmonary
      parenchyma, or bronchi. Untreated aneurysms will cause death in the majority of
      patients because of rupture. Recent data evaluating smaller and asymptomatic
      thoracic aneurysms with CT scan support nonoperative management and close follow
      up of descending and thoracoabdominal aortic aneurysms only when the diameter is
      less than 5 cm. Patients with Marfan syndrome may be operated upon with smaller
      aneurysms. Independent of etiology, operative repair is the most effective means
      to alter the otherwise malignant course of descending and thoracoabdominal aortic
      aneurysms. The role of endovascular repair of these aneurysms remains to be
      established; however, it may represent an alternative to treat thoracic
      aneurysmal disease in very high risk patients.

PMID- 9271759
TI  - Identification of risk factors in patients undergoing thoracoabdominal aneurysm
      repair.
AB  - Developments and advances in surgical and anesthetic techniques have lead to
      increased survival in patients undergoing complex thoracic aortic aneurysm
      repairs. The decision to operate, however, continues to be based in a large
      degree on the clinical impression of the patient's ability to withstand the
      rigors of the procedure. As part of the ongoing effort of our department to
      further elucidate those parameters that impart added risk to patients, the
      diameters and volumes of CT-imaged aortas were determined for 67 surgical and
      nonoperatively managed patients. Significant differences were found between those
      patients not requiring surgery, and both those undergoing operation and those
      that died of rupture. Similarly, the average yearly increase in volume in
      surgical and rupture patients was higher than that of nonoperatively managed
      patients. Those patients who smoked also were found to have a significant yearly
      increase in size of their aortas relative to those patents that did not. An
      algorithm for managing patients presenting with thoracoabdominal aneurysms based
      upon size at initial presentation, change in annual diameter and volume, and
      estimated risk for paraplegia is presented.

PMID- 9271760
TI  - Pathophysiology of cerebral injury and future management.
AB  - Central nervous system dysfunction continues to represent significant morbidity
      and associated mortality in patients undergoing cardiac surgery. Neurological
      dysfunction is most exaggerated in patients undergoing hypothermic circulatory
      arrest (HCA). Although surgical techniques, anesthetic management, and
      postoperative care have significantly improved over the past two decades, the
      incidence of stroke and other neurocognitive deficits remains problematic.
      Understanding the mechanisms of cell death associated with HCA may provide
      information that is germane to all types of cerebral injury involved in cardiac
      surgery. Using a closed-chest cardiopulmonary bypass model, dogs underwent 2
      hours of circulatory arrest at 18 degrees C followed by resuscitation and
      recovery for 3 days. Animals were assessed functionally by a species-specific
      behavioral scale, histologically for patterns of selective neuronal necrosis and
      receptor autoradiography for NMDA glutamate receptor subtype expression. Using a
      selective NMDA (-glutamate) receptor antagonist (MK801), an AMPA-antagonist
      (NBQX) and a nonspecific neuroprotectant (GM1-ganglioside), the role of glutamate
      excitotoxicity in the development of HCA-induced brain injury was documented and
      validated. Using a similar canine preparation, a microdialysis technique was used
      to evaluate the role of nitric oxide in neuronal death. Arginine plus oxygen is
      converted to nitric oxide plus citrulline by the action of nitric oxide synthase.
      Simultaneous infusion of artificial cerebrospinal fluid containing L-[14C]
      arginine or L-[14C] arginine and L-NAME (a nitric oxide synthase inhibitor) was
      performed in contralateral hemispheres. Citrulline recovery in the cerebrospinal
      fluid, citrulline production in vitro from canine cortical homogenates, and
      nitric oxide metabolites in the serum were all significantly increased during HCA
      and reperfusion. These studies demonstrated that neurotoxicity following HCA
      involves a significant and early induction of neuronal NOS expression and
      neuronal processes leading to widespread augmented NO production in the brain.
      Continued research into the pathophysiologic mechanisms involved in cerebral
      injury will undoubtedly yield a safe and reliable neuroprotectant strategy.

PMID- 9271761
TI  - Use of hypothermic circulatory arrest for cerebral protection during aortic
      surgery.
AB  - Optimal use of hypothermic circulatory arrest during aortic surgery requires
      understanding of its physiology. Research in laboratory animals and clinical
      observations have now documented that considerable residual cerebral metabolism
      remains with cooling to levels of 15-18 degrees C, especially if cooling
      intervals are short, reflected by persistent jugular venous desaturation. Cooling
      should be continued to below 15 degrees C if the duration of HCA is expected to
      exceed 20 minutes, and continued until jugular venous saturations exceed 95%.
      There is considerable laboratory evidence that even short durations of HCA are
      followed by a prolonged interval of increased cerebral vascular resistance during
      which cerebral metabolism is maintained at normal levels by markedly increased
      oxygen extraction. Clinical observations have now confirmed that considerable
      jugular venous desaturation is present in patients following HCA: it is more
      pronounced with prolonged HCA, and is still present as late as six hours after
      the start of rewarming. This reinforces the concept of a prolonged postoperative
      vulnerable interval following HCA, during which any compromise in oxygen delivery
      has the potential for producing cerebral injury. Several adjunctive measures have
      been shown to improve outcome following HCA. The simplest and most important is
      topical hypothermia: packing the head in ice during the interval of HCA.
      Retrograde cerebral perfusion (RCP) has also been shown to improve EEG recovery
      as well as histological and behavioral outcome in laboratory animals following
      prolonged HCA, but some of its effect may be secondary to its efficacy in keeping
      the brain cold, since RCP provides very low rates of flow and supports metabolism
      at a much lower level than antegrade perfusion at the same temperature. But
      despite the clear superiority of antegrade perfusion, and the documentation of
      some benefits of RCP in laboratory measures of cerebral protection, clinical
      results using RCP and ACP have not yet demonstrated the superiority of these
      methods over use of HCA alone, perhaps because these modalities are usually
      employed in patients with unusually high risk of neurological injury: those with
      dissection or with clot or atheroma in the aorta. Nevertheless, recent years have
      seen considerable reduction in mortality following aortic surgery, especially in
      older patients, and a trend toward a lower incidence of permanent neurologic
      dysfunction. The presence of preoperative rupture or hemodynamic compromise, and
      of clot or atheroma in the aorta, remain the most significant risk factors both
      for death and occurrence of stroke.

PMID- 9271762
TI  - Experience with retrograde cerebral perfusion during proximal aortic surgery in
      290 patients.
AB  - BACKGROUND: We currently routinely use profound hypothermic circulatory arrest
      (PHCA) with retrograde cerebral perfusion (RCP) during repair of proximal aortic
      dissection and aneurysms involving the transverse aortic arch. Experimental data
      regarding the efficacy of RCP are conflicting. We retrospectively reviewed our
      experience with proximal aortic surgery to compare the results of PHCA performed
      with and without RCP. PATIENTS AND METHODS: From January 1987 through July 1996,
      590 patients underwent ascending or transverse aortic arch operations. Of the 479
      patients who required PHCA, RCP was utilized in 290 (60.5%). The patients who did
      not receive RCP had a higher prevalence of preexisting cerebrovascular disease,
      diabetes, and aortic dissection than those who did. RESULTS: Overall 30-day and
      in-hospital mortality rates were 7.9% (38/479) and 8.8% (42/479), respectively;
      six (1.3%) intraoperative deaths were excluded from the analysis regarding
      neurologic complications. There were 19 strokes (4.0%). Comparing the patients
      who had RCP with those who did not, 30-day mortality rates were 3.4% (10/290) vs.
      14.8% (28/189, p < 0.001), in-hospital mortality rates were 3.4% (10/290) vs.
      16.9% (32/189, p < 0.001), and stroke rates were 2.4% (7/289) vs. 6.5% (12/184, p
      < 0.05), respectively. CONCLUSIONS: Patients who had RCP during PHCA had lower
      mortality and stroke rates than those who did not. Although the higher prevalence
      of cerebrovascular disease, diabetes, and dissection in the latter group may have
      contributed to these differences, the clinical results confirm the safety and
      potential benefits of RCP, further supporting its use during proximal aortic
      surgery requiring circulatory arrest.

PMID- 9271763
TI  - Brain protection.

PMID- 9271764
TI  - Exercise intolerance in congestive heart failure: a lesson in exercise
      physiology.
AB  - The current working hypothesis of exercise intolerance in patients with CHF
      indicates that an initial reduction in cardiac output, secondary to either
      systolic or diastolic dysfunction, results in a variety of complex and inter
      related pathophysiologic alterations in the skeletal muscle, the vasculature, the
      pulmonary system, and several neurohumoral systems. These numerous compensatory
      mechanisms, although they work to preserve vital body functions, they ultimately
      result in exercise intolerance. Thus, the syndrome of CHF provides a unique
      opportunity to evaluate the role of several fundamental principles of exercise
      physiology.

PMID- 9271765
TI  - Cost-effectiveness of cardiac rehabilitation after myocardial infarction.
AB  - BACKGROUND: Cardiac rehabilitation is commonly prescribed after myocardial
      infarction (MI) to coordinate exercise training and secondary preventive
      services. Cost-effectiveness analysis allows the quantitative comparison of the
      relative economic worth of cardiac rehabilitation in relation to other common
      interventions. METHODS: The cost-effectiveness of cardiac rehabilitation, in
      dollars per year of life saved ($/YLS), was calculated by combining published
      results of randomized trials of cardiac rehabilitation on mortality rates,
      epidemiologic studies of long-term survival in the overall postinfarction
      population, and studies of patient charges for rehabilitation services and
      averted medical expenses for hospitalizations after rehabilitation. RESULTS:
      Cardiac rehabilitation participants experienced an incremental life expectancy of
      0.202 years during a 15-year period. In 1988, the average cost of rehabilitation
      and exercise testing was $1,485, partially offset by averted cardiac
      rehospitalizations of $850 per patient. A cost-effectiveness value of 2,130 $/YLS
      was determined for the late 1980s, projected to a value of 4,950 $/YLS for 1995.
      A sensitivity analysis supports the study results. CONCLUSIONS: Compared with
      other post-MI treatment interventions, cardiac rehabilitation is more cost
      effective than thrombolytic therapy, coronary bypass surgery, and cholesterol
      lowering drugs, though less cost-effective than smoking cessation programs.
      Cardiac rehabilitation should stand alongside these therapies as standard of care
      in the post-MI setting.

PMID- 9271767
TI  - A controlled trial of circuit weight training on aerobic capacity and myocardial
      oxygen demand in men after coronary artery bypass surgery.
AB  - BACKGROUND: Cardiovascular benefits of resistance training in cardiac patients
      have been suggested but not studied in a randomized, controlled trial of circuit
      weight training (CWT) without an aerobic exercise component. The purpose of the
      current study was to examine the effects of 10 weeks of CWT on muscular strength,
      peak oxygen consumption (peak VO2), and myocardial oxygen demand (mVO2) in men
      after coronary artery bypass surgery. METHODS: Twenty-six, post-coronary bypass
      male subjects (mean 19 months after bypass), aged 60 +/- 8.5 years, were randomly
      allocated to 10 weeks of CWT at 40 to 60% of maximum voluntary contraction (n =
      12) or to a control group (n = 14). Muscular strength was assessed using a
      modified one repetition maximum technique. Peak VO2 was recorded during symptom
      limited treadmill exercise. Rate pressure product, as an indirect measure of
      mVO2, was measured during isometric, isodynamic, and dynamic exercise. RESULTS:
      No ischemic symptoms nor electrocardiographic changes were recorded during
      testing or training. Strength increased by 18% (P < 0.005) in five out of seven
      exercises in the training group, but was unchanged in the control group. Training
      did not improve peak VO2. Rate pressure product during isometric and isodynamic
      exercise decreased from pre- to post-testing (P < 0.05) but was equivalent to
      that seen in the control group. CONCLUSIONS: Moderate intensity CWT is safe and
      can improve strength in selected low-risk patients after coronary artery bypass
      surgery. However, it does not significantly increase peak VO2 nor reduce mVO2
      during isometric, isodynamic, and dynamic exercise.

PMID- 9271766
TI  - Improved skeletal muscle performance after individualized exercise training in
      patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: In addition to the respiratory limitation in patients with chronic
      obstructive pulmonary disease (COPD), skeletal muscle abnormalities may occur and
      contribute to the exercise intolerance. This study assessed the ability of the
      skeletal muscle of patients with COPD to adapt to individualized exercise
      training at the gas exchange threshold (GET) METHODS: Fourteen patients (8 in a
      training group and 6 controls) performed the following exercise tests before and
      after a 3-week training period: an incremental exercise test, maximal voluntary
      contraction of the quadriceps, and three endurance tests consisting of dynamic
      contractions of the quadriceps until exhaustion. These endurance tests,
      characterized by three different power outputs, were used to determine muscle
      limit times and critical power. RESULTS: The results showed that training
      increased exercise tolerance (+11% for symptom limited peak oxygen consumption
      (VO2 sl], P < 0.05), maximum voluntary contraction (+8%, P < 0.05), limit times
      (from +45% to +161%, P < 0.05) and critical power (+39%, P < 0.05). CONCLUSIONS:
      These findings indicate greater muscle strength and endurance after training in
      COPD patients and suggest better muscular recruitment and improved oxidative
      capacity in the exercising muscles. The sharp differences in the magnitude of VO2
      sl and limit times suggest that the kinetics of peripheral and central changes in
      response to training are different. In conclusion, peripheral muscle performance
      can be increased rapidly in response to an individualized training program at the
      GET in COPD patients.

PMID- 9271768
TI  - Analysis of chronic obstructive pulmonary disease referrals for lung volume
      reduction surgery. The University of California San Diego Emphysema Treatment
      Group.
AB  - BACKGROUND: Preliminary results of lung volume reduction surgery (LVRS) for
      patients with severe emphysema are promising, although many issues regarding the
      selection process for LVRS are still unaddressed. For example, it is unclear
      which patients should be referred for pulmonary rehabilitation, lung
      transplantation, or LVRS, and whether health-care providers are optimizing
      conservative treatment options before referral for surgical intervention. The
      purpose of this analysis is to describe preliminary results of the evaluation
      process for LVRS implemented as part of an integrated, programmatic approach to
      the evaluation, treatment, and rehabilitation of patients with advanced
      emphysema. METHODS: The records of 105 consecutive patients with chronic
      obstructive pulmonary disease (COPD) referred for consideration for LVRS at the
      University of California San Diego Medical Center were reviewed. Results of
      prospective data collection pertaining to patient demographic, baseline dyspnea
      scores, and history of prior treatment, including pulmonary rehabilitation, were
      extracted. Patient disposition after the evaluation was noted. RESULTS: One
      hundred five patients (mean age 65 years, range 40 to 84 years) completed
      evaluation. Fifty-eight had never before participated in pulmonary
      rehabilitation, and 47 of these patients were eventually referred to a
      rehabilitation program. Fourteen patients were referred for consideration of lung
      transplantation, 25 were considered eligible for LVRS, 13 were still undergoing
      rehabilitation and surgical eligibility had not yet been determined, and 53 were
      ineligible for LVRS because patients had other illnesses (n = 34), did not meet
      radiological or physiologic criteria (n = 5), were considered too ill (n = 5), or
      were too healthy (n = 9) after rehabilitation to warrant surgical intervention.
      CONCLUSIONS: Lung volume reduction surgery is a surgical option to be considered
      within the framework of an integrated medical evaluation program that includes
      pulmonary rehabilitation. Pulmonary rehabilitation remains an often underused
      therapeutic alternative in patients with severe COPD. It has become the central
      component of our comprehensive management program for patients with severe
      dyspnea and deteriorating quality of life.

PMID- 9271769
TI  - Who needs an exercise stress test? Evaluating the new American College of Sports
      Medicine risk stratification guidelines.
AB  - PURPOSE: The American College of Sports Medicine recently published new
      guidelines to classify individuals at increased risk for coronary heart disease
      (CHD) before starting a vigorous (> 60% maximum oxygen consumption) exercise
      program. We compared the prognostic value of the new guidelines to the earlier
      guidelines. METHODS: Subjects included men and women over 30 years of age, free
      from known CHD according to the Lipid Research Clinic Follow-up Cohort. Endpoints
      included an abnormal exercise test result (+/- 1 mm ST, anginal chest pain, or
      exercise hypotension) and future death of CHD ascertained during an average 12.2
      years of follow-up. Data analysis included 2 x 2 contingency tables to compare
      the test characteristics of the old and new guidelines. RESULTS: Among 4,074
      subjects, 219 (5.4%) had abnormal exercise test results and 65 (1.6%) eventually
      died of CHD. The new guidelines classified 75.7% of individuals as high risk
      versus 58.7% using the old guidelines. Comparing the new guidelines with the old,
      test sensitivity was significantly (P = 0.007) higher for patients with an
      abnormal exercise test result (87% versus 77%) than for patients who died of CHD
      (100% versus 99%). Test specificity of the new guidelines was significantly (P <
      0.001) lower than the old guidelines for individuals with abnormal exercise test
      results (25% versus 42%) and those who died of CHD (25% versus 42%). The new
      guidelines also showed significantly lower overall diagnostic accuracy and
      positive likelihood ratios compared with the old guidelines for both patients
      with abnormal exercise test results and those who died of CHD. The positive
      predictive value for the new and old guidelines for both patients with abnormal
      exercise test results and those who died of CHD were similar. CONCLUSIONS:
      Although the new guidelines are more sensitive in the abnormal exercise test
      result endpoint, they are less specific and overall less accurate than the old
      guidelines given the low prevalence of CHD in this asymptomatic population. The
      current guidelines should be modified to better target high-risk adults.

PMID- 9271770
TI  - Validity of rating of perceived exertion during graded exercise testing in
      apparently healthy adults and cardiac patients.
AB  - PURPOSE: Recent exercise guidelines recommend a generalized rating of perceived
      exertion (RPE) range of 12 to 16 (15-point Borg scale) as the perceptual range
      associated with a physiological training effect. However, whether an individual
      who selects an RPE within the generalized range during an graded exercise test or
      exercise training, is actually within the correlated physiological range (50 to
      85% maximum oxygen consumption [VO2max]) has not been studied in large samples of
      apparently healthy individuals or cardiac patients. The purpose of the present
      study was to assess the validity of the generalized RPE recommendations in a
      large heterogeneous group of apparently healthy subjects and cardiac patients.
      METHODS: Subjects included apparently healthy adults (N = 463) and cardiac
      patients (N = 217) who presented for a sign-symptom limited maximal graded
      exercise test (SSLMGXT). Ratings of perceived exertion associated with relative
      exercise intensities of 60 and 80% of maximal heart rate reserve (MHRR) and peak
      exercise were selected for analyses. RESULTS: Significant interindividual
      variability in RPE was observed at both relative exercise intensities (6 to 20
      RPE range at 60% MHRR; 8 to 20 RPE range at 80% MHRR) for both populations.
      Thirty-nine percent of healthy subjects and 32% of cardiac patients reported an
      RPE outside an 11 to 14 range at 60% of MHRR, whereas 32% of healthy subjects and
      52% of cardiac patients reported an RPE outside of a 14 to 17 range at 80% of
      MHRR. Peak RPE was higher for the apparently healthy subjects compared with the
      cardiac patients (18.8 +/- 1.2 versus 16.5 +/- 1.8; P < 0.01). CONCLUSIONS: These
      results challenge the applicability of the generalized RPE recommendations
      described in recent exercise guidelines under typical clinical exercise testing
      conditions. The basis for the generalized RPE recommendations warrant further
      investigation. Those who desire to use RPE as a marker of relative exercise
      intensity during SSLMGXT should take into consideration the large interindividual
      variability in these measures.

PMID- 9271771
TI  - Acupressure as an adjunct to a pulmonary rehabilitation program.
AB  - BACKGROUND: Acupressure is a therapy in which gentle pressure is applied with
      fingers at specific acupoints on the body. It is reported to relieve pain and
      have other beneficial effects. This study was designed to ascertain the value of
      self-administered acupressure as an adjunct to a pulmonary rehabilitation program
      (PRP) for relief of dyspnea and other symptoms in patients with chronic
      obstructive pulmonary disease (COPD). METHODS: A single-blind pretest-posttest,
      cross-over design was used. Thirty-one new patients beginning a 12-week PRP at
      two private hospitals were randomly assigned to one of two groups. Patients in
      group 1 were taught acupressure and practiced it daily at home for 6 weeks, then
      sham acupressure for the following 6 weeks. In group 2, the order of acupressure
      and sham acupressure was reversed. During weeks 1, 6, and 12, patient dyspnea,
      other symptoms associated with COPD, activity tolerance, lung function, and
      functional exercise capacity were assessed. RESULTS: Real acupressure was more
      effective than sham acupressure for reducing dyspnea as measured by a visual
      analog scale (P = .009, one-tailed), and was minimally effective for relieving
      decathexis (P = .044, one-tailed). Sham acupressure seemed to be more effective
      than real acupressure for reducing peripheral sensory symptoms (P = .002, two
      tailed), but the presence of these symptoms may also be an indication that the
      acupressure is affecting the body. CONCLUSIONS: Acupressure seems to be useful to
      patients with COPD as an adjunct to a PRP in reducing dyspnea. Some persons who
      are not initially familiar with traditional Chinese medicine can learn and will
      accept self-administered acupressure as part of their self-care.

PMID- 9271772
TI  - Secondary prevention: no more exercise?

PMID- 9271773
TI  - The use of the telephone in cardiac and pulmonary rehabilitation.

PMID- 9271774
TI  - American College of Sports Medicine Exercise Specialist Workshop/Certification: a
      model for career preparation.

PMID- 9271775
TI  - Urinary excretion of cortisol, norepinephrine, testosterone, and melatonin in
      panic disorder.
AB  - Nocturnal urinary cortisol, norepinephrine, epinephrine, testosterone, and
      melatonin secretion patterns were studied in male patients with DSM IV/ICD-10
      panic disorder (n = 16) over two series of 5 consecutive nights each. Night-time
      urinary excretion of cortisol, norepinephrine, and epinephrine was significantly
      elevated in drug-free patients compared to normal individuals (n = 13).
      Measurements were repeated after 4 weeks, and the same differences were found
      again. There were high correlations between the first and the second series of
      measurements. Testosterone and melatonin levels did not differ between panic
      patients and controls.

PMID- 9271777
TI  - Longtime administration of growth hormone-releasing hormone (GHRH) does not
      restore the reduced efficiency of GHRH on sleep endocrine activity in 2 old-aged
      subjects--a preliminary study.
AB  - Aging results in a more shallow sleep accompanied by a blunted growth hormone
      (GH) secretion. In young male normal controls repetitive administration of GH
      releasing hormone (GHRH) at the beginning of the night results in an increased
      secretion of GH, a blunting of cortisol and a stimulation of slow-wave sleep
      (SWS). In healthy elderly men and women, however, GHRH exerts only weak effects
      on sleep-endocrine activity. In a previous report continuous treatment of healthy
      elderly males by repetitive administration of GHRH (during 12 days administration
      with 100 micrograms GHRH i.v. at 9.00 h every second day, "priming") enhanced
      GHRH stimulated GH secretion at daytime markedly. We tested if priming with GHRH
      results in a more distinct modulation of the nocturnal hormone secretion and of
      the sleep EEG than acute administration of the peptide. Two elderly male controls
      spent first three consecutive nights in the sleep laboratory, the first of which
      served for adaptation to laboratory conditions. During the two other nights (at
      days 1 and 2) sleep EEG was recorded and blood was sampled for determining the
      secretion of GH, cortisol and ACTH. In one of the nights the subjects received 50
      micrograms GHRH hourly between 22.00 h and 1.00 h (4 x 50 micrograms) or placebo.
      The next examination followed after the priming period at day 14 and the last was
      performed two weeks after treatment at day 28. After the baseline administration
      of 4 x 50 micrograms GHRH before priming no clear changes of sleep EEG towards
      improved sleep were detectable, whereas GH secretion was increased. After priming
      sleep period time and SWS time were lower compared to the baseline night with
      GHRH administration, whereas REM time duration increased. GHRH induced GH
      secretion was not enhanced after priming. ACTH secretion was markedly enhanced
      compared to baseline stimulation. We conclude that priming with GHRH has no sleep
      improving effect and does not change hormone secretion in elderly normal
      subjects. Hence in the elderly priming with GHRH is not capable to induce a
      rejuvenation of sleep endocrine activity.

PMID- 9271776
TI  - The influence of clozapine treatment on plasma granulocyte colony-stimulating (G
      CSF) levels.
AB  - The antipsychotic drug clozapine frequently induces transient increases in white
      blood cell counts that have been found to be sensitive, but non-specific,
      predictors of subsequent life-threatening agranulocytosis. Granulocyte colony
      stimulating factor (G-CSF) is an endogenous hematopoietic growth factor that
      plays a pivotal role in granulopoiesis. In addition, G-CSF has successfully been
      used to treat clozapine-induced agranulocytosis. We performed a longitudinal
      investigation of the plasma levels of G-CSF in 20 schizophrenic patients during
      six weeks of clozapine treatment. Clozapine transiently increased plasma G-CSF
      levels in 55% of the subjects studied. This effect was most prominent at the end
      of the second week of treatment. Increased G-CSF levels were accompanied by
      increased granulocyte and monocyte counts, increased rectal temperature and
      increased plasma levels of other cytokines and cytokine receptors. The results
      presented suggest that G-CSF is involved in clozapine-induced increases in
      granulocyte counts seen early during treatment. Like granulocytosis,
      granulocytopenia is known to occur in conjunction with increased systemic G-CSF
      levels. Therefore, we hypothesize that a persistent increase along with a decline
      in white cell counts following an early spike during clozapine treatment might
      predict the occurrence of agranulocytosis.

PMID- 9271778
TI  - Trimipramine and maprotiline plasma levels during combined treatment with
      moclobemide in therapy-resistant depression.
AB  - In an open pilot study of 21 therapy-resistant depressive inpatients, plasma
      levels of antidepressants were determined during treatment with a combination of
      moclobemide/ trimipramine (n = 15) and moclobemide/maprotiline (n = 6). After
      combined administration of trimipramine and moclobemide (MCB), a significant
      increase in the plasma level of trimipramine (39%) was observed. After
      combination of maprotiline with moclobemide, maprotiline levels were increased
      (25%, n.s.). The results show that moclobemide, as an inhibitor of isoenzymes of
      the cytochrome P 450 oxidase, can cause increases in the plasma levels of
      tricyclic and tetracyclic antidepressants. No correlation between the serum level
      of the antidepressants and treatment outcome was found in this open study.

PMID- 9271779
TI  - Monitoring serum concentrations of clomipramine and metabolites: fluorescence
      polarization immunoassay versus high performance liquid chromatography.
AB  - This study compared fluorescence polarization immunoassay (FPIA) with a high
      performance liquid chromatographic (HPLC) method from the point of view of their
      applicability to therapeutic drug monitoring of patients treated with
      clomipramine alone. Blood was withdrawn from 20 depressed inpatients (54 +/- 14
      years) under steady state conditions. The FPIA determined total tricyclic
      antidepressant (TCA) concentrations with day to day variability below 11%. The
      automated HPLC method separated clomipramine, N-desmethylclomipramine, 8
      hydroxyclomipramine and 8-hydroxydesmethylclomipramine with interassay
      coefficients of variance below 12%. The concentrations measured by FPIA were
      similar to HPLC results. Total TCA concentrations measured by FPIA and the sum of
      clomipramine and desmethylclomipramine measured by HPLC correlated significantly
      (r = 0.780 and p < 0.01). However, 40% of individual FPIA determinations yielded
      results that differed by more than 50% from the HPLC concentrations. Changes in
      clinical rates were related only to TCA serum concentrations that had been
      analyzed by HPLC. It is concluded that the semiquantitative FPIA is unsuitable
      for therapeutic drug monitoring in patients under clomipramine treatment, whereas
      the differential analysis of clomipramine and metabolites by HPLC is informative
      and can be used to improve the antidepressant drug treatment.

PMID- 9271780
TI  - Paroxetine and galactorrhea.
AB  - The authors report a case of galactorrhea following antidepressant treatment
      where paroxetine might be responsible. Paroxetine is a selective serotonergic
      reuptake inhibitor (SSRI). Galactorrhea occasionally is a dopamine-mediated side
      effect observed with neuroleptic drugs. However, the ability to produce
      extrapyramidal side effects is known for tricyclic as well as for SSRIs. Thus the
      potential of SSRIs to induce dopamine-dependent side effects is a clinical
      reality and it was not surprising to observe galactorrhea due to paroxetine.
      However, in a review of the literature no reported cases of galactorrhea
      associated with paroxetine were found.

PMID- 9271781
TI  - Risperidone in treatment-refractory chronic alcohol hallucinosis.

PMID- 9271782
TI  - Characterization of functional interaction of carboxylic acid group of agonists
      and arginine of the seventh transmembrane domains of four prostaglandin E
      receptor subtypes.
AB  - Prostaglandin (PG) E2 binds to four PGE receptor subtypes, EP1, EP2, EP3 and EP4,
      and induces a variety of functions through the interaction of carboxylic acid of
      PGE2 and Arg residue in the seventh transmembrane domain of the receptor. To
      assess the role of the interaction of the carboxylic acid group of agonists and
      the Arg residue, which can form both ionic bonding and hydrogen bonding as a
      hydrogen donor, we examined the agonist activities of three types of agonist,
      PGE2 with a negatively charged carboxylic acid, PGE2 methylester, which is a
      hydrogen acceptor, and 1-OH PGE2, which can accept as well as donate hydrogen but
      prefers to donate hydrogen rather than accept it, for four PGE receptor subtypes.
      Although PGE2 methylester had slightly lower agonist activities than PGE2 for EP1
      and EP4 receptors, PGE2 and its methylester showed the same agonist activities
      for EP2 and EP3 receptors, indicating that PGE2 methylester is a potent agonist
      for all of the four subtypes. In contrast, 1-OH PGE2 was a very weak agonist for
      all receptors. These findings demonstrate that the hydrogen bonding interaction
      of agonists and the Arg residue is generally sufficient for the functional
      activation of all of the PGE receptor subtypes.

PMID- 9271784
TI  - Prostaglandin D synthase concentration in cerebrospinal fluid and serum of
      patients with neurological disorders.
AB  - Prostaglandin D synthase (PGD synthase) or beta-trace protein is a major
      constituent of human cerebrospinal fluid (CSF) representing-3% of the total CSF
      protein. We have recently developed a highly specific immunofluorometric assay
      for PGD synthase, which enabled us to quantify the presence of PGD synthase in
      fluids and tissues not associated with the CNS. In this report we provide
      quantitative data of the presence of PGD synthase in CSF and serum from 302
      subjects with various neurological diseases and symptoms. PGD synthase levels in
      CSF are approximately 35-fold higher than those of serum, with a median
      concentration of 11,299 micrograms/L. A statistically significant association of
      PGD synthase concentration in CSF was observed with both patient age and gender.
      There was no correlation between PGD synthase concentration in serum and patient
      age or gender. To evaluate the clinical utility of PGD synthase in diagnosing
      neurological diseases, the distribution pattern of PGD synthase in CSF and serum
      was examined for each neuropathology of 268 patients whose diagnosis was known.
      No statistical difference was observed between PGD synthase concentration in the
      CSF (129 cases) or the serum (94 cases) of multiple sclerosis afflicted subjects
      in comparison to all other patients studied. The distribution pattern was also
      not different for PGD synthase levels in CSF of patients with HIV/AIDS related
      neuropathies, viral meningitis and fibromyalgia. We conclude that PGD synthase
      measurement presents no clinical utility in diagnosing neurological disorders in
      adulthood. PGD synthase may have a physiological and/or pathological role in the
      developing brain and in neurodegenerative diseases.

PMID- 9271783
TI  - The ratio of formation of prostacyclin/thromboxane A2 in HUVEC decreased in each
      subsequent passage.
AB  - In this study, we analyzed the antioxidative potential (SOD-, GSH-Px-activity)
      and the basal, H2O2- and ATP-stimulated formation of PGI2 and TXA2 in human
      umbilical vein endothelial cells (HUVEC) of different passages. The
      subcultivation of cells partly represents the process of aging. Both
      subcultivation of the cells and the H2O2 incubation did not significantly
      influence the activity of SOD and GSH-Px. H2O2 (0.1 mM and 1.0 mM) stimulated the
      generation of PGI2 and TXA2 in the cell passages time dependently. The formation
      ratio of PGI/TXA2 changed from 640:1 (0.1 mM H2O2) or 430:1 (1.0 mM H2O2, 40 min
      incubation) at the 1st passage, to 13:1 and 17:1, respectively, at the 4th
      passage. This resulted from the reduction of the PGI2 synthesis connected with
      more pronounced TXA2 formation. The same behavior was found in the basal and ATP
      stimulated eicosanoid formation. Based on this, the age-dependent activation of
      the oxygen radical formation could be responsible for the modified eicosanoid
      metabolism resulting in vascular complications in the elderly.

PMID- 9271785
TI  - Involvement of Rho family proteins in prostaglandin F2 alpha-induced
      phospholipase D activation in the osteoblast-like cell line MC3T3-E1.
AB  - To examine the role of Rho family proteins in prostaglandin F2 alpha (PGF2 alpha)
      mediated phospholipase D (PLD) activation of osteoblast-like cell line MC3T3-E1
      cells, we used Toxin-B from Clostridium difficile, which inhibits Rho family
      proteins by monoglucosylation. Pretreatment of [3H]myristic acid-labeled MC3T3-E1
      cells with Toxin B induced rounding-up of the cells and inhibited the PGF2 alpha
      induced PLD activation by 60%, but not the phospholipase C (PLC) activation.
      Cytochalasin D also induced rounding the cells, but showed a small inhibition in
      the PLD activation. Brefeldin A (BFA) had marginal inhibitory effect on the PGF2
      alpha-induced PLD activation. In digitonin-permeabilized MC3T3-E1 cells, [3H]P
      But formation was stimulated by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S)
      or 4 beta-phorbol 12-myristate 13-acetate (PMA) in the presence of Ca2+ (1
      microM) and ATP (1 mM), and phosphatidylinositol 4,5-bisphosphate (PIP2) was also
      required for its full PLD activation. Pretreatment of the digitonin-permeabilized
      MC3T3-E1 cells with Toxin B reduced the GTP gamma S- and PMA-stimulated PLD
      activities by 80% and 60%, respectively. On the other hand, C3 toxin which
      inhibits Rho by ADP-ribosylation, exerted a partial inhibitory effect on the GTP
      gamma S-stimulated PLD activity. These results suggest that Cdc42 as well as RhoA
      appear to be involved in the PLD activation mediated by PGF2 alpha and also that
      the PLD activation may be independent of actin cytoskeleton in MC3T3-E1 cells.

PMID- 9271786
TI  - Oxidative stress and the mobilisation of arachidonic acid in stimulated human
      platelets: role of hydroxyl radical.
AB  - Platelet functions, including eicosanoid biosynthesis, can be significantly
      altered by exposure to reactive oxygen species. We utilised the redox properties
      of the phenazine derivative, pyocyanin, to generate low micromolar levels of
      reactive oxygen species in order to investigate the metabolism of arachidonic
      acid by human platelets under oxidative stress. Eicosanoid production by
      platelets, pre-labelled with [3H]arachidonic acid (AA) and stimulated with the
      calcium ionophore A23187, was inhibited in the presence of pyocyanin. In
      contrast, platelets pre-treated with pyocyanin and concurrently exposed to A23187
      and AA showed no evidence of inhibition. Analysis of the free label content of
      labelled, pyocyanin-treated platelets after stimulation revealed diminished
      levels of total free label and a corresponding increase in labelled phospholipid.
      Prior treatment with the antioxidants, superoxide dismutase, catalase or the
      hydroxyl radical scavenger, mannitol, before the addition of pyocyanin afforded
      protection against loss of eicosanoid production and restored AA release. We
      conclude that hydroxyl radicals inhibit one or more steps in the cascade leading
      to phospholipase A2 activation and release of arachidonic acid from platelet
      phospholipid stores.

PMID- 9271787
TI  - Benzodiazepine receptors in the post-mortem brain of suicide victims and
      schizophrenic subjects.
AB  - To examine the role of benzodiazepine (BZ) receptors in suicide and
      schizophrenia, we determined BZ receptors in post-mortem brain (Brodmann's area
      10) obtained from suicide victims, schizophrenic patients, and control subjects
      using [3H]RO15-1788 as the radioligand. The maximum number of binding sites
      (Bmax) of BZ receptors in the cortex of suicide victims was significantly higher
      compared with controls, but this increase was mainly due to those suicide victims
      who died by violent means and whose Bmax was significantly higher than of those
      who died by non-violent means or control subjects. In schizophrenic patients,
      Bmax was not significantly different from that of control subjects. When the
      schizophrenic subjects were separated into two groups, those on neuroleptics and
      those off neuroleptics for at least 12 months, however, the mean Bmax of BZ
      receptors in the prefrontal cortex in post-mortem brain obtained from
      schizophrenic patients on neuroleptics was significantly lower than Bmax in drug
      free schizophrenic patients or normal controls. There were no significant
      differences among groups in values of the apparent dissociation constant (KD) of
      [3H]RO15-1788 binding. These results suggest that BZ receptors are up-regulated
      in the cortex of suicide victims, specifically those who used violent means, and
      that neuroleptic treatment may result in decreased central BZ receptor binding in
      the cortex of schizophrenic patients. Thus, the method of suicide and previous
      exposure to neuroleptics should be considered in the interpretation of data on BZ
      receptors.

PMID- 9271788
TI  - Circadian profiles of melatonin in melancholic depressed patients and healthy
      subjects in relation to cortisol secretion and sleep.
AB  - Circadian secretion of melatonin was measured in melancholic depressed patients
      (n = 9) and age- and sex-matched healthy control patients (n = 9). The mean age
      of the depressed patients was 29 years, i.e. younger than in most earlier
      studies, and a drug-free interval of 3 weeks preceded the investigations.
      Melatonin secretion was similar in depressed patients and healthy subjects with
      no significant differences at any of the time points, thus not confirming earlier
      studies in which depressed patients were found to have lower melatonin levels
      than control patients. The discrepancy between our result and earlier studies may
      be explained by different patient characteristics such as age, duration of
      illness, previous treatment, and alcohol intake. It is conceivable that a
      diminution of nocturnal melatonin secretion in depressed patients might only
      occur during the long-term course of the depressive illness and/or its
      pharmacological treatment.

PMID- 9271789
TI  - Genetic and developmental factors in spontaneous selective attention: a study of
      normal twins.
AB  - The Spontaneous Selective Attention Task (SSAT) is a visual word identification
      task designed to measure the type of selective attention that occurs
      spontaneously when there are multiple stimuli, all potentially relevant, and
      insufficient time to process each of them fully. These are conditions which are
      common in everyday life. SSAT performance is measured by word identification
      accuracy, first under a baseline divided attention condition with no
      predictability, then under a selective attention condition with partial
      predictability introduced via word repetition. Accuracy to identify novel words
      in the upper location which becomes partially predictable (P words) vs. the lower
      location which remains non-predictable (N words) can be used to calculate a
      baseline performance index and a P/N ratio measure of selective attention. The
      SSAT has been shown to identify an attentional abnormality that may be useful in
      the development of an attentional endophenotype for family-genetic studies of
      schizophrenia. This study examined age and genetic effects on SSAT performance in
      normal children in order to evaluate whether the SSAT has the potential to
      qualify as a candidate endophenotype for schizophrenia in studies of at-risk
      children. A total of 59 monozygotic twin pairs and 33 same-sex dizygotic twin
      pairs ranging from 10 to 18 years of age were tested on the SSAT, a Continuous
      Performance Test. (CPT), a Span of Apprehension Test (SPAN) and a full-scale IQ
      test. Baseline performance on the SSAT, which was correlated with verbal IQ and
      SPAN performance, improved with age but showed no significant heritability. The
      P/N selectivity ratio was stable over the 10-18-year age range, was not
      significantly correlated with IQ, CPT, or SPAN performance, and its heritability
      was estimated to be 0.41. These findings suggest that the P/N selectivity ratio
      measured by the SSAT may be useful as a vulnerability marker in studies of
      children born into families segregating schizophrenia.

PMID- 9271790
TI  - Subject and informant variables affecting family history diagnoses of depression
      and dementia.
AB  - The aim of the present study was to evaluate subject and informant factors
      affecting the validity of the family history for dementia and depression.
      Relatives of patients and control subjects (n = 531) were interviewed directly.
      At least one 'significant' other provided family history information on every
      interviewed relative. The detection of dementia or depression based on the family
      history increased with the severity of the respective disorder. The likelihood of
      detecting dementia based on the family history increased in proportion to the
      subject's age. A lifetime diagnosis of depression in the informant improved the
      detection of this disorder in a relative. The presence of another psychiatric
      disorder in either the interviewed relative or the informant significantly
      increased the risk for false-positive diagnoses of depression. The present
      results demonstrate that family history information on depression and dementia is
      influenced by different proband and informant variables. On the basis of these
      results, we cannot recommend reducing thresholds for family history diagnoses.

PMID- 9271791
TI  - Cluster analytic validation of the DSM melancholic depression. The threshold
      model: integration of quantitative and qualitative distinctions between unipolar
      depressive subtypes.
AB  - Cluster analysis was performed on the DSM-III symptoms of major depression and
      symptoms of melancholia identified in a study group consisting of 220 unipolar
      depressed inpatients a melancholic and non-melancholic cluster. Patients
      allocated to the melancholic cluster were more severely depressed and they were
      characterized by psychomotor disorders, a distinct quality of mood, diurnal
      variation, early morning awakening, and non-reactivity. Our results support the
      construct validity of the DSM-III melancholic subtype of major depression. This
      study supports the integrated threshold model:. (i) melancholic and non
      melancholic depression may be regarded as continuous classes in terms of overall
      severity of depression; and (ii) both groups form discrete categories with regard
      to the melancholic symptoms, which emerge as the severity of depression
      increases.

PMID- 9271792
TI  - Personality differences between obsessive-compulsive disorder subtypes: washers
      versus checkers.
AB  - Personality differences between 'washer' and 'checker' subtypes of obsessive
      compulsive disorder (OCD) were explored. Fifty-one OCD patients were recruited
      from several outpatient clinics in Central Israel. OCD was diagnosed according to
      DSM-III-R using the Structured Clinical Interview for DSM-III-R, and personality
      disorders were diagnosed using the Structured Clinical Interview for DSM-III-R
      Personality Disorders. Washers were much more likely to have personality
      disorders than checkers. Personality disorders were diagnosed in 12 of 13 washers
      vs. three of 11 checkers (chi 2 = 10.75, Fisher's exact test, P < 0.001, d.f. =
      1, odds ratio = 32, CI = 2.8-365) and 21 of 27 patients with mixed OCD symptoms.
      The results support the validity of the washer-checker subdivision and might
      explain the relative refractoriness of washers to conventional intervention.

PMID- 9271793
TI  - Comparing a sample proportion with a specified population proportion based on the
      mid-P method.
AB  - A common practice for determining whether a sample proportion is statistically
      different from a specified population proportion is using the exact probability
      procedure. However, it produces overly conservative confidence intervals and p
      values. A stand-alone executable program is written for applying alternative
      approaches based on the mid-P and bootstrap methods.

PMID- 9271794
TI  - Neutron versus gamma-ray risk estimates. Inferences from the cancer incidence and
      mortality data in Hiroshima.
AB  - While it is recognized that neutrons contributed to the excess cancer incidence
      and mortality among the atomic bomb survivors in Hiroshima, there is no
      possibility to deduce the magnitude of this contribution from the data. This
      remains true even if the neutron doses in the dosimetry system DS86 are corrected
      upwards in line with recent neutron activation measurements. In spite of this
      fact, important information can be obtained in the form of an inverse relation of
      the risk coefficients for gamma-rays and neutrons. Such an interrelation must
      apply because the observed excess incidence or mortality is made up of a gamma
      ray and a neutron component; increased attribution to neutrons decreases the
      attribution to photons. Computations with the uncorrected and the corrected DS86
      are performed for the mortality and the incidence of solid tumors combined. They
      refer to doses up to 2 Gy and employ the constant relative risk model and a
      linear-quadratic dose dependence with variable ratio-the neutron relative
      biological effectiveness (RBE) at low doses-of the linear component for neutrons
      and gamma-rays. In line with past analyses, no quadratic component is obtained
      with the uncorrected DS86. but it is seen, even in these calculations, that the
      assumption of increased neutron RBEs does not translate into proportional
      increases of the risk coefficients of neutrons, because it leads to substantially
      reduced risk estimates for gamma-rays. Calculations with the corrected dosimetry
      bring out this reciprocity even more clearly. High values of the neutron RBE
      reduce-in line with recent suggestions by Rossi and Zaider-the risk estimates for
      gamma-rays substantially. Even a purely quadratic dose relation for gamma-rays is
      consistent with the data; it requires no major increase of the nominal risk
      coefficients for neutrons over the currently assumed values. The cancer data from
      Hiroshima can still provide 'prudent' risk estimates for photons, but with the
      corrected DS86, they do not prove that there is a linear component in the dose
      dependence for photons.

PMID- 9271795
TI  - Radiogenic lung cancer: the effects of low doses of low linear energy transfer
      (LET) radiation.
AB  - A critical review of the literature leads to the conclusion that at the radiation
      doses generally of concern in radiation protection (< 2 Gy), protracted exposure
      to low linear energy transfer (LET) radiation (x- or gamma-rays) does not appear
      to cause lung cancer. There is, in fact, indication of a reduction of the natural
      incidence.

PMID- 9271796
TI  - Biophysical analysis of the dose-dependent overdispersion and the restricted
      linear energy transfer dependence expressed in dicentric chromosome data from
      alpha-irradiated human lymphocytes.
AB  - Experimental data for the induction of dicentric chromosomes in
      phytohemagglutinin (PHA)-stimulated human T lymphocytes by 241Am alpha-particles
      obtained by Schmid et al. have been analyzed in the light of biophysical theory.
      As usual in experiments with alpha-particles, the relative variance of the
      intercellular distribution of the number of aberrations per cell exceeds unity,
      and the multiplicity of the aberrations per particle traversal through the cell
      is understood as the basic effect causing this overdispersion. However, the
      clearly expressed dose dependence of the relative variance differs from the dose
      independent relative variance predicted by the multiplicity effect alone. Since
      such dose dependence is often observed in experiments with alpha-particles,
      protons, and high-energy neutrons, the interpretation of the overdispersion needs
      to be supplemented. In a new, more general statistical model, the distribution
      function of the number of aberrations is interpreted as resulting from the
      convolution of a Poisson distribution for the spontaneous aberrations with the
      overdispersed distributions for the aberrations caused by intratrack or
      intertrack lesion interaction, and the fluctuation of the cross-sectional area of
      the cellular chromatin must also be considered. Using a suitable mathematical
      formulation of the resulting dose-dependent over-dispersion, the mean number
      lambda 1 of the aberrations produced by a single particle traversal through the
      cell nucleus and the mean number lambda 2 of the aberrations per pairwise
      approach between two alpha-particle tracks could be estimated. Coefficient alpha
      of the dose-proportional yield component, when compared between 241Am alpha
      particle irradiation and 137Cs gamma-ray exposure, is found to increase
      approximately in proportion to dose-mean restricted linear energy transfer, which
      indicates an underlying pairwise molecular lesion interaction on the nanometer
      scale.

PMID- 9271797
TI  - DNA complex lesions induced by protons and alpha-particles: track structure
      characteristics determining linear energy transfer and particle type dependence.
AB  - The yield of DNA double-strand breaks (dsb) and DNA complex lesions induced by
      protons and alpha-particles of various energies was simulated using a Monte Carlo
      track structure code (MOCA15) and a simple model of the DNA molecule. DNA breaks
      of different complexity were analysed. The linear energy transfer (LET) and
      particle-type dependence of lesions of higher complexity seems to confirm the
      importance of clustered damage in DNA as a relevant step leading to biological
      endpoints such as cell inactivation. The detailed structure of proton and alpha
      particle tracks was analysed to identify the main characteristics possibly
      responsible for such a dependence. The role of the primary ion and of its
      secondary electrons in inducing dsb and complex lesions is described, showing
      that the relative contribution of secondary electron tracks alone in inducing
      clustered lesions is almost negligible at high LET, but tends to dominate below =
      10 keV/micron. This is consistent with the observed similar effectiveness of low
      LET fast particle radiation and sparsely ionizing radiation such as x-rays. The
      dependence on LET and particle type is mainly due to energy deposition events of
      the primary ion together with short range electrons surrounding the ion track;
      the yield of complex lesions due to secondary electron tracks alone is
      substantially LET independent. The radial distributions of the energy
      contributing to the induction of complex lesions were analyzed and compared with
      the radial distributions of energy deposition of the full tracks. The results
      suggest that the stochastic behaviour (i.e. cluster properties) of the energy
      deposition pattern within a radius of a few nanometers around the ion track plays
      a relevant role in determining the biological radiation effectiveness.

PMID- 9271798
TI  - Monte Carlo simulation of physicochemical processes of liquid water radiolysis.
      The effects of dissolved oxygen and OH scavenger.
AB  - The paper describes developments of the physicochemical part of a computer code
      system that estimates DNA strand break induction on plasmid pBR322 DNA. In order
      to test the reliability of the model, we evaluated the dielectric function and
      the time-dependent yield of chemical species in the presence of OH radical
      scavenger or dissolved oxygen. Results agree with measurements on the radiolysis
      of liquid water. When a hybrid model of a liquid inelastic cross-section and a
      vapour elastic cross-section is used, energy deposition by vibrational
      excitations is estimated to be approximately 11% of total energy deposition.

PMID- 9271799
TI  - Overexpression of insulin-like growth factor (IGF)-I receptor enhances inhibition
      of DNA replication in mouse cells exposed to x-rays.
AB  - Previous studies from our laboratory provided evidence for the operation of
      signal transduction pathways involving ras, myc, and staurosporine-sensitive
      protein kinases in the regulation of DNA replication in irradiated cells. Because
      ras and myc are also involved in the signal transduction elicited in response to
      ligand activation of growth factor receptors, we wondered whether growth factor
      receptors are upstream elements in the regulation of DNA replication in
      irradiated cells. Here, we report on the role of insulin-like growth factor I
      receptor (IGF-IR) in the regulation of DNA replication in irradiated cells. We
      compare radiation-induced inhibition of DNA replication in BALB/c 3T3 cells with
      that in P6 cells. P6 cells are derived from BALB/c 3T3 cells by transfection with
      a vector expressing IGF-IR, leading to 30-fold overexpression. We observe a
      significantly stronger inhibition of DNA replication after irradiation in P6 as
      compared with BALB/c 3T3 cells at all doses examined. Sedimentation in alkaline
      sucrose gradients shows that the increased inhibition in P6 cells is due to an
      increased inhibition of replicon initiation, the main controlling event in DNA
      replication. Staurosprine at 20 nM reduces radiation-induced inhibition of DNA
      replication in BALB/c 3T3 cells, but has only a small effect in P6 cells.
      Caffeine at a concentration of 1 mM, on the other hand, removes over 60% of the
      inhibition in both cell lines. The results implicate IGF-IR in the regulation of
      DNA replication in irradiated cells, but also suggest differences between cells
      of different origins in the proteins involved in the regulating signal
      transduction pathway.

PMID- 9271800
TI  - Effects of lithium chloride as a potential radioprotective agent on radiation
      response of DNA synthesis in mouse germinal cells.
AB  - Mouse spermatogonial germ cells are highly sensitive to ionizing radiation.
      Lithium salts are reported to stimulate the postirradiation recovery of
      hematopoietic marrow cells. We have, therefore, examined whether administered
      lithium chloride (LiCl) would also be able to protect the mouse germinal cells
      against radiation injury. Taking DNA synthesis as an endpoint, our results show
      that the testicular DNA-specific activity in irradiated mice was higher by 61% on
      average when they had been pretreated with LiCl both 24 h and 1 h prior to gamma
      irradiation (2.0 Gy). It was also observed that the DNA synthetic activity in the
      germinal cells fully recovered after LiCl pretreatment at doses of 40 mg per kg
      body weight prior to total body irradiation of 0.05-0.25 Gy, whereas at doses of
      0.5-6.0 Gy, following the same procedure of LiCl pretreatment, only an incomplete
      recovery was observed. The dose reduction factor for LiCl is 1.84. The current
      findings indicate that pretreatment with LiCl provides considerable protection
      against radiation damage in mouse spermatogonia.

PMID- 9271802
TI  - A response to "Perinatal mortality in Germany following the Chernobyl accident".

PMID- 9271801
TI  - Perinatal mortality in Bavaria, Germany, after the Chernobyl reactor accident.
AB  - As has been shown by the authors of a paper recently published in this journal, a
      deviation from a long-term trend in perinatal mortality within the former Federal
      Republic of Germany occurred in 1987, i.e. 1 year following the Chernobyl
      disaster. It is the aim of this study to make a comparison between the areas of
      the state Bavaria. Germany, with different fallout levels as well as between the
      observed and expected numbers of perinatal deaths relating to these areas. The
      expected numbers of perinatal deaths, defined as external standard, were derived
      from the remainder of the former FRG. Testing an a priori formulated hypothesis
      revealed no differences in the temporal development of perinatal mortality
      between the areas with different fallout levels and subsequent exposure.
      Including May 1986 into the analysis revealed a significant increase during the
      first 3 months after the accident, which is due to an excess in May alone. Since
      no elevated radiation risks for the last days in utero are known, the additional
      Chernobyl radiation exposure is not plausible as a causative agent. Further
      analyses on stillbirths showed an increase in Southern Bavaria during the first 2
      years following the accident. Later on, the rates were comparable to the expected
      values again.

PMID- 9271803
TI  - Mechanisms underlying stimulation of rapidly adapting receptors during pulmonary
      air embolism in dogs.
AB  - We investigated the mechanisms underlying stimulation of rapidly adapting
      receptors (RARs) during pulmonary air embolism (PAE). Impulses were recorded from
      RARs in 43 anesthetized, open-chest and artificially ventilated dogs. Forty one
      out of 56 RARs were stimulated by infusion of air into the right atrium (0.2
      ml/kg per min for 10 min). As a group (n = 56), RAR activity increased from a
      baseline of 1.2 +/- 0.2 to a peak of 4.3 +/- 0.3 impulses/breath at 8-10 min
      after the onset of PAE induction. PAE also caused an increase in total lung
      resistance and a decrease in dynamic lung compliance. Studies were repeated in 33
      RARs initially stimulated by PAE. In nine receptors, hyperinflation of the lungs
      performed at the termination of the second PAE induction largely reversed both
      the afferent and bronchomotor responses. Furthermore, the residual PAE-evoked
      activity subsequent to hyperinflation was almost eliminated by elevation in the
      heart position. In another 24 receptors, the responses of RARs to PAE were
      unaltered by pretreatment with saline (n = 8) or dimethylthiourea (a hydroxyl
      radical scavenger; n = 8), but was significantly attenuated by pretreatment with
      ibuprofen (a cyclooxygenase inhibitor: n = 8). These results suggest that: (1)
      the increased RAR activity following PAE is associated primarily with an increase
      in bronchomotor tone and secondarily with the mechanical action of the beating
      heart impacting on lung tissues; and (2) cyclooxygenase products may be involved
      in this sensory stimulation.

PMID- 9271804
TI  - Ventilation and respiratory mechanics during exercise in younger subjects
      breathing CO2 or HeO2.
AB  - To determine if ventilation (VE) during maximal exercise would be increased as
      much by 3% CO2 loading as by resistive unloading of the airways, we studied seven
      subjects (39 +/- 5 years; mean +/- S.D.) during graded-cycle ergometry to
      exhaustion while breathing: (1) room air (RA); (2) 3% CO2, 21% O2, and 76% N2; or
      (3) 79% He and 21% O2). VE and respiratory mechanics were measured during each 1
      min increment (20 or 30 W) in work rate. VE during maximal exercise was increased
      21 +/- 17% when breathing 3% CO2 and 23 +/- 16% when breathing HeO2 (P < 0.01).
      Further, the ventilatory response to exercise above ventilatory threshold (VTh)
      was increased (P < 0.05) when breathing HeO2 (0.89 +/- 0.26 L/min/W) as compared
      with breathing RA (0.65 +/- 0.12). When breathing HeO2, end-expiratory lung
      volume (% total lung capacity, TLC) was lower during maximal exercise (46 +/- 7)
      when compared with RA (53 +/- 6, P < 0.01). In conclusion, VE during maximal
      exercise can be augmented equally by 3% CO2 loading as by resistive unloading of
      the airways in younger subjects. This suggests that in younger subjects with
      normal lung function there are minimal mechanical ventilatory constraints on VE
      during maximal exercise.

PMID- 9271805
TI  - Carbon dioxide respiratory response during positive inspiratory pressure in COPD
      patients.
AB  - The aim of this study was to compare the effect of inspiratory pressure support
      (IPS) on the respiratory CO2 response in 13 stable COPD patients and in 13 normal
      subjects. Without IPS, the slopes of the ventilatory response to CO2 were lower
      in the patients than in the normal subjects (mean +/- SEM, 0.82 +/- 0.19 vs. 1.69
      +/- 0.31 l.min-1.mmHg-1). When IPS was applied, both groups showed, at any level
      of end-tidal CO2 pressure, an increase in ventilation due to an increase in tidal
      volume (VT) associated with a decrease in occlusion pressure (P0.1). In addition,
      respiratory parameters (VE, VT, P0.1, inspiratory flow) were insensitive to CO2
      as long as PETCO2 remained below a threshold which was slightly above the eupneic
      value. However, above this CO2-threshold, no differences in slopes were observed
      between the IPS and control conditions in either group, except for a decrease in
      the P0.1 slope during IPS in the COPD patients. In conclusion, IPS induced
      similar respiratory changes during CO2 response in stable COPD patients and in
      normal subjects. Above the eupneic value, IPS did not change the slope of the
      ventilatory response to CO2.

PMID- 9271806
TI  - Chronic hypoxia affects capillary density and geometry in pigeon pectoralis
      muscle.
AB  - We examined fiber capillarization and ultrastructure in pectoralis muscle of 11
      pigeons (Columbia livia; body mass 603 +/- 12 (SE) g) i.e. nine birds kept at
      3800 m for 5 months (three in a small aviary (A1) and five in smaller cages, A2)
      compared to three sea-level (SL) controls. There was no difference between groups
      in either the relative area or number of aerobic and glycolytic fibers per total
      fibers, fiber size or mitochondrial volume density. Hematocrit was significantly
      greater in A1 and A2 (59 +/- 1%) than SL (50 +/- 2%). In A1, capillary density
      relative to the sectional area of aerobic/total fibers, capillary diameter and
      the contribution of tortuosity and branching to capillary length were
      significantly greater than SL, yielding greater capillary length and surface area
      per volume of fiber. Capillary length and surface densities very close to those
      in A1 and significantly greater than SL for the relative sectional area of
      aerobic/total fibers were also found in four out of five A2 birds, without
      alteration in capillary geometry or diameter. The size of the capillary-fiber
      interface (i.e. capillary-to-fiber surface ratio) in aerobic fibers was also
      greater in A1 and A2 than SL, indicating a greater capacity for oxygen supply of
      the muscle fibers in the altitude groups.

PMID- 9271807
TI  - Effects of PEEP on respiratory mechanics are tidal volume and frequency
      dependent.
AB  - How the effects of frequency, tidal volume (VT) and PEEP interact to determine
      the mechanical properties of the respiratory system is unclear. Airway flow and
      airway and esophageal pressures were measured in ten intubated,
      anesthetized/paralyzed patients during mechanical ventilation at 10-30
      breaths/min and VT of 250-800 ml. From these measurements, Fourier transformation
      was used to calculate elastance (E) and resistance (R) of the total respiratory
      system (subscript rs), lungs (subscript L) and chest wall (subscript cw) at 5, 10
      and 0 cm PEEP. As PEEP increased from 0-5 cmH2O, all elastances and resistances
      decreased (P < 0.05). Increasing PEEP to 10 cmH2O decreased EL, Rrs, and RL
      further (P < 0.05). The changes in Ers, EL, Rrs and RL caused by PEEP were less
      (P < 0.05) as VT increased, while changes in Rrs, RL and Ers were less (P < 0.05)
      as frequency increased. VT dependences in Ers and Rrs were enhanced (P < 0.05) at
      0 cmH2O PEEP. The ratio of EL to chest wall elastance was not affected by PEEP (P
      > 0.05), but increased (P < 0.05) with increasing VT at 5 and 10 cmH2O PEEP. We
      conclude that it is critical to standardize ventilatory parameters when comparing
      groups of patients or testing clinical intervention efficacy and that the
      differential effects on the lungs and chest wall must be considered in optimizing
      the application of PEEP.

PMID- 9271808
TI  - Dry gas hyperpnea changes airway reactivity and ion content of rabbit tracheal
      wall.
AB  - Dry air hyperventilation provokes airway narrowing in asthmatics. The mechanism
      is thought to involve the release of inflammatory mediators in response to airway
      osmolarity. The response to inhaled histamine on lung mechanics and the ion
      content of the airway subepithelial connective tissue after dry gas
      hyperventilation was investigated in rabbits. Resistance increased more after
      histamine given after hyperventilation with dry gas compared to humid gas (P <
      0.05). Compliance decreased after histamine for both dry and humid gas
      hyperventilation. The Na, Cl and K content was decreased in the tissue at 4 min
      (P < 0.001) and nearly returned to resting content at 8 min of hyperventilation
      with dry gas. The results suggest that dehydration occurred and was followed by
      oedema formation in the tracheal wall. Thus, the effects of inhaled histamine on
      airway resistance was amplified. The mechanism involved may be part of the normal
      defence of the airway to protect against desiccation during hyperventilation with
      dry air. This response may be exaggerated in asthmatics.

PMID- 9271809
TI  - Structural and biochemical characteristics of locomotory muscles of emperor
      penguins, Aptenodytes forsteri.
AB  - Structural and biochemical characteristics of the primary muscles used for
      swimming (pectoralis, PEC and supracoracoideus, SC) were compared to those of leg
      muscles in emperor penguins (Aptenodytes forsteri). The mass of PEC-SC was four
      times that of the leg musculature, and mitochondrial volume density in PEC and SC
      (4%) was two-thirds that in sartorius (S) and gastrocnemius. The differences in
      muscle mass and mitochondrial density yielded a 2.2-fold greater total
      mitochondrial content in PEC-SC than leg muscles, which appears to account for
      the 1.8-fold greater whole-body highest oxygen consumption previously recorded in
      emperor penguins during swimming compared to walking. Calculation of maximal
      mitochondrial O2 consumption in PEC-SC and leg muscle yielded value of 5.8-6.9 ml
      O2 ml-1 min-1, which are similar to those in locomotory muscles of most mammals
      and birds. A distinct feature of emperor penguin muscle was its myoglobin
      content, with concentrations in PEC-SC (6.4 g 100 g-1 among the highest measured
      in any species. This resulted in a PEC-SC O2 store greater than that of the
      entire blood. In addition, ratios of myoglobin content to mitochondrial volume
      density and to citrate synthase activity were 4.4 and 2.5 times greater in PEC
      than in S, indicative of the significant role of myoglobin in the adaptation of
      muscle to cardiovascular adjustments during diving.

PMID- 9271810
TI  - In vivo determination of surface tension in the horse trachea and in vitro model
      studies.
AB  - We measured the surface tension in the trachea of the non-anaesthetised horse
      from the spreading behaviour of fluid drops, using videotracheoscopy. To do this,
      we placed small oil drops onto the tracheal wall with a thin Teflon tubing
      inserted into a videocolonoscope used in humans. Either 5 ml of saline (control)
      or 5 ml of bovine lipid extract surfactant (BLES) at 4 mg/ml were administered.
      Tracheal surface tension was 31.9 +/- 0.54 mN/m (Mean +/- SEM, n = 30) in the
      control experiments and 24.5 +/- 0.51 mN/m (Mean +/- SEM, n = 21) in the entire
      trachea after the administration of BLES. These values were determined from
      calibration curves relating film surface tension to the relative diameter of test
      fluid droplets. In the calibration experiments, the test fluid droplets were
      placed onto a surfactant film at various surface tensions in either a modified
      Langmuir-Wilhelmy balance or a captive bubble surfactometer. The spreading
      behaviour of a given test fluid droplet in the model studies did not only depend
      on the film surface tension but also on the thickness of the aqueous layer below
      the surfactant film. Hence, the computed surface tensions in the trachea depend
      on the choice of which in vitro model is applied.

PMID- 9271811
TI  - Reevaluating the effects of tyrosine iodination of recombinant hirudin on its
      thrombin inhibition kinetics.
AB  - To reevaluate the effects of iodination of hirudin on its thrombin-inhibiting
      activity, we iodinated a recombinant hirudin analog, CX-397, by a chloramine-T
      method and isolated the eight kinds of iodinated derivatives by reverse-phase
      HPLC. Their structure were different combinations of non-, mono-, or di-iodinated
      residues at Tyr-3 and Tyr-64. Their ability to inhibit alpha-thrombin were
      determined and compared with each other. Iodination at Tyr-64 slightly increased
      the association rate constant (Kon) 1.26- to 1.79-fold; this may be explained by
      the increase in the negative charge at C-terminal region of CX-397 caused by the
      electrophilic ortho substitution of Tyr-64 with iodine. On the contrary,
      iodination at Tyr-3 caused dual effects on the interaction between CX-397 and
      alpha-thrombin; namely, mono-iodination at Tyr-3 caused a small decrease in Koff
      (1.29- to 1.63-fold) than non-iodinated ones, whilst di-iodination at Tyr-3
      brought about 3.04- to 3.88-fold increase in Koff. Since the N-terminal region of
      hirudin has been reported to bind with thrombin by hydrophobic interaction, the
      destabilizing effect of di-iodination at Tyr-3 can be explained by the increase
      in its polar nature, whereas the opposite effect of mono-iodination can not.
      These results indicate that it is not appropriate to use a mixture of variably
      radioiodinated hirudins as a radiotracer. We also provide a simple method to
      obtain well characterized radioiodinated hirudins.

PMID- 9271812
TI  - The reliability of thrombotic tendency measured by intravascular wires in the
      rat.
AB  - The objective was to determine if the amount of thrombus on two adjacent wires in
      an artery or in a vein was similar, and whether an upstream wire affected
      thrombosis on the downstream wire. Two 2 cm platinum wires were placed at
      adjoining sites in the abdominal vena cava and a further 2 in the abdominal aorta
      in 26 male and 24 female rats. In the artery, mean thrombus weight on the aortic
      downstream wire, set where the vessel is narrow, was significantly (p < 0.001)
      less than on the upstream wire, but the two correlated fairly well correlation
      coefficient (r = 0.608). In the vein, mean thrombus weight deposited in 1 hour
      was comparable on the pairs of wires both in males (r = 0.819) and females (r =
      0.805). The mean downstream thrombus was slightly (10%) heavier than the upstream
      one both in males and females, a possible effect of vessel diameter, or of an
      activation by the upstream wire of thrombosis on the downstream one. An
      experiment to clarify that issue showed mean downstream venous thrombus to be
      again heavier than mean up-stream in both sexes (22 males, 30 females), and
      heavier than in controls in which no upstream wire was inserted. The platinum
      wire venous model seems to measure individual thrombotic response in a reasonably
      reproducible way in the rat. Upstream venous wire appears to activate thrombosis
      downstream from it by some 10%.

PMID- 9271813
TI  - Quantitation of the thrombotic effects in artery and vein of the increase in
      coagulation factors during normal pregnancy in the rat.
AB  - Coagulation factors increase and fibrinolysin activity decreases in pregnant
      women. While the nett change in thrombotic tendency is unmeasured, venous
      thromboembolism increases five-fold in this group. We measured thrombus formation
      in vein and artery on standard platinum wires in 45 near-term pregnant rats, 19
      pregnant for the first time and 26 for the second time, and in 33 never-pregnant
      controls. No significant increase in arterial thrombus occurred in the pregnant
      rats. Venous thrombus, however, increased by 65% in rats pregnant for the first
      time and 176% in those pregnant for the second time, compared to never-pregnant
      animals. Their mean increase in coagulation factors VIII, X, V, VII and II varied
      from 165 to 268%. Factor VIII level (r = 0.59, p < 0.05) correlated with venous
      thrombosis level, but the rarity of spontaneous thrombosis did not permit the
      limits of risk to be determined. Factors VII, X and V showed little correlation
      with thrombus weight (r = < 0.16) and Factor II an insignificant one. Monitoring
      factor VIII levels in pregnant women might help identify a group at risk of
      thromboembolism and establish a threshold for prophylactic intervention.

PMID- 9271814
TI  - Endothelial eicosanoid metabolism and signal transduction during exposure to
      oxygen radicals injury.
AB  - Several physiological agonists that induce elevation of cytosolic free calcium
      (Ca2+)-levels act via receptor coupled G-proteins, involving activation of
      phospholipase C (PLC) and hydrolysis of phosphatidylinositol 4,5-bisphosphate.
      Activation of the inositol signal transduction pathway that precedes Ca2+ ion
      mobilization is a well accepted signaling pathway in endothelial cell eicosanoid
      synthesis. This study was designed to examine possible involvement of
      phosphoinositides in the effects of oxygen free radicals on Ca2+ liberation and
      eicosanoid synthesis in human umbilical venous endothelial cells (HUVEC).
      Hydrogen peroxide (H2O2) was chosen as oxygen radicals generating agent.
      Stimulation of HUVEC with H2O2 (0.1 mmol/l) led to significant rises in inositol
      phosphate and diacylglycerol (DAG) levels within 300 seconds and an inhibition of
      Ca2+ release from internal stores. Eicosanoid formation was detectable despite
      unchanged levels of cytosolic free Ca2+ and no detectable activation of membrane
      associated phospholipase A2 (PLA2). This suggests that eicosanoid formation may
      be mediated through the activation of a Ca2+ independent, cytosolic 40 kDa PLA2
      isoenzyme and that DAG could serve as an alternative source for arachidonic acid
      and seems to sensitize a cytosolic PLA2.

PMID- 9271815
TI  - High prevalence of antithrombin III, protein C and protein S deficiency, but no
      factor V Leiden mutation in venous thrombophilic Chinese patients in Taiwan.
AB  - We studied the prevalence of antithrombin III (AT III), protein C (PC) and
      protein S (PS) deficiencies and factor V Leiden mutation in thrombophilia in
      Taiwan. Eighty-five consecutive and unrelated patients with otherwise unexplained
      venous thrombophilia were studied. Both antigen and activity of inhibitors were
      determined using commercial kits (Stago), activated PC sensitivity ratio (APC SR)
      by Coatest (Chromogenix), and factor V mutation by polymerase chain reaction with
      sequence specific primer. Of 85 patients, 41 were male, 44 female, and mean age
      49.4 years (17-82 years). None had factor V mutation, or APC SR of less than 2;
      50 (58.8%) showed a deficiency of inhibitor proteins; 34 (68.0%) were hereditary,
      16 (32.0%) non-hereditary; 3 had an AT III deficiency, 16 a PC deficiency, 28 a
      PS deficiency, and 3 a combined deficiency. Thirty-five were non-deficient
      without a known cause. The average age at the first thrombotic episode was 48.5
      years (13-81 years). Thrombosis occurred spontaneously in 39 (78.0%) of 50
      deficient patients. In conclusion, a relatively higher prevalence of AT III, PC
      and PS deficiency (59%), but no factor V Leiden mutation, was found in venous
      thrombophilic Chinese patients in Taiwan compared to that in western countries.
      Screening for inhibitor protein deficiency in Chinese thrombophilic patients is
      highly recommended.

PMID- 9271816
TI  - A novel variant of staphylokinase gene from Staphylococcus aureus ATCC 29213.
AB  - The processes of hemostasis and thrombolysis are elegantly regulated in order to
      ensure normal functions of vascular system. A search for new plasminogen
      activators as thrombolytic agents has been carried out for the purpose of
      clinical applications to modulate thrombolytic processes. In the current work,
      several strains and clinical isolates of Staphylococcus aureus were screened for
      the fibrinolytic activity. The DNA sequences of staphylokinase gene in the
      strains expressing 15 kDa protein with staphylokinase activity were determined
      and subsequently compared with three known staphylokinase gene sequences. From
      the sequence comparison a new variant of staphylokinase gene has been identified
      in ATCC 29213 strain. The gene product needs to be further characterized and
      tested for the therapeutic potential.

PMID- 9271817
TI  - Fluvastatin and tissue factor pathway inhibitor in type IIA and IIB
      hyperlipidemia and in acute myocardial infarction.
AB  - Tissue factor pathway inhibitor (TFPI) is a serine protease inhibitor that
      regulates tissue factor-induced blood coagulation. In an open-label 8-week study,
      20 hypercholesterolemic patients (10 type IIa and 10 type IIb) were enrolled and
      given fluvastatin 40 mg once daily at bedtime. At baseline (after a 4-week
      controlled diet) and at week 8, total cholesterol, total triglycerides and
      lipoprotein subfractions were assessed. TFPI antigen levels were measured at the
      same time by ELISA. We also measured TFPI concentrations in 10 control subjects
      and in 10 patients at the time of and ten days after acute myocardial infarction.
      In type IIa patients fluvastatin reduced total cholesterol levels by 26% and LDL
      cholesterol by 30% (P < 0.001); in type IIb, fluvastatin significantly reduced
      total cholesterol levels by 24% (P < 0.001). In both dyslipidemic groups the
      baseline total TFPI levels were significantly higher than in the control group (P
      < 0.002). The therapeutic lipid-lowering effect was paralleled by a significantly
      reduction of total TFPI antigen concentrations from 132 +/- 23 to 71 +/- 37 ng/mL
      (P < 0.001) in type IIa and from 120 +/- 30 to 91 +/- 29 ng/mL (P < 0.05) in type
      IIb patients; in control subjects total TFPI levels were 81 +/- 22 ng/mL; however
      the lipoprotein-bound TFPI antigen subfractions did not differ significantly in
      the treated and control groups. In patients with recent myocardial infarction
      there was a significant reduction from day 0 to day 10 in total TFPI antigen
      levels, from 120 +/- 48 ng/mL to 80 +/- 16 ng/mL (P < 0.05). The reported
      reduction of TFPI antigen levels after fluvastatin treatment could be a sign of
      normalization of an up-regulated clotting system rather than an unfavourable
      reduction of a natural anticoagulant.

PMID- 9271819
TI  - Hyperhomocysteinemia following oral methionine load is associated with increased
      lipid peroxidation.

PMID- 9271818
TI  - Differential effect of a low-molecular-weight heparin (dalteparin) and
      unfractionated heparin on platelet interaction with the subendothelium under flow
      conditions.
AB  - Effects of heparins on platelet function are controversial, but perfusion
      studies, that simulate physiological conditions, might help to explain their
      clinical behaviour. We used a perfusion system to test the effect unfractionated
      heparin and a low-molecular-weight heparin (dalteparin, Fragmin) on platelet
      adhesion promoted by a damaged vascular surface. Normal blood samples containing
      increasing concentrations of unfractionated heparin and dalteparin were perfused
      through annular chambers containing enzymatically denuded rabbit aorta segments
      (5 min at 800 sec-1). Segments were evaluated morphometrically measuring the
      total surface covered by platelets and by large aggregates (thrombi).
      Unfractionated heparin inhibited platelet interaction with subendothelium in a
      lesser extent than dalteparin in both covered surface and thrombi (p < 0.01). At
      heparin doses that caused maximal inhibition covered surface was 10.0% +/- 3.1%
      with dalteparin and 18.3% +/- 4.2% with unfractionated heparin, and thrombi were
      5.6% +/- 3.2% and 12.3% +/- 3.0%, respectively. These results may collaborate to
      explain some differences observed in the clinical results obtained with
      unfractionated heparin and with dalteparin.

PMID- 9271820
TI  - Maternal DRB1*1501, DQA1*0102, DQB1*0602 haplotype in fetomaternal
      alloimmunization against human platelet alloantigen HPA-6b (GPIIIa-Gln489).
AB  - Fetomaternal incompatibility of platelet alloantigens may lead to
      alloimmunization and neonatal alloimmune thrombocytopenia (NAIT). Human platelet
      alloantigen (HPA) 6b, which associates with residue Gln 489 of platelet membrane
      glycoprotein IIIa, has been described as a cause of NAIT. We have studied the MHC
      genes of all available family members in the six thus far reported families with
      a thrombocytopenic newborn and fetomaternal HPA-6b incompatibility. Maternal HPA
      6b antibodies could be detected in five mothers to the altogether seven
      thrombocytopenic male infants. The MHC genes HLA-DRB, -DQA1, -DQB1, -DPB1, TAP1,2
      and HSP70-Hom were studied by using polymerase chain reaction (PCR)-based DNA
      analysis methods. All five mothers with detectable circulating HPA-6b antibodies
      at the time of delivery shared an identical DRB1*1501, DQA1*0102, DQB1*0602
      haplotype. The sixth, HPA antibody negative mother and a HPA-6b-negative mother
      to a healthy HPA-6b+ child were negative for this haplotype. The frequency of
      DRB1*15-positive haplotype was increased in immunized mothers (100%) as compared
      with the general Finnish population (27%), but the association was not
      statistically significant after correction. We conclude that there is a potential
      association between the MHC haplotype DRB1*1501, DQA1*0102, DQB1*0602 and
      alloimmunization to the HPA-6b antigen and that this alloimmunization probably
      involves different HLA class II molecules from immunization to HPA-1a.

PMID- 9271821
TI  - HLA homozygosity and the risk of graft-versus-host disease.
AB  - We explored the relationship between HLA homozygosity and risk of graft-versus
      host disease (GVHD) after allogeneic marrow transplantation from an HLA
      genotypically identical sibling. If the variety of minor histocompatibility
      antigens is decreased by the restricted diversity of major histocompatibility
      complex (MHC) molecules capable of presenting allogeneic peptides in HLA
      homozygous individuals, then the risk of GVHD should be decreased in comparison
      to HLA-heterozygous marrow transplant recipients. Contrary to expectations, we
      found that HLA-homozygous individuals and HLA-heterozygous individuals have
      comparable risks of GVHD. We propose that the unexpectedly high incidence of GVHD
      in HLA-homozygous individuals can be explained by determinant density effects
      that enable certain peptide-MHC complexes to function as minor antigens on HLA
      homozygous antigen-presenting cells but not on HLA-heterozygous antigen
      presenting cells. Thus the variety of minor antigens expressed by the two types
      of cells might be similar, despite the differences in the diversity of HLA
      molecules.

PMID- 9271822
TI  - Molecular analysis of HLA polymorphism in Khoton-Mongolians.
AB  - We have investigated polymorphism of the HLA class I and class II genes in
      Mongolians for the first time using PCR-based techniques. A minor population of
      Khoton-Mongolians was studied and compared to the major Khalkh-Mongolian
      population. Eighty-five Khoton- and 41 Khalkh-Mongolian samples were analyzed for
      polymorphism in HLA-A, -B, -DRB1, -DRB3, -DRB5, -DQA1, -DQB1, -DPA1, and -DPB1
      loci using PCR-SSOP and PCR-RFLP methods. Allele and haplotype frequencies were
      calculated. The results were then compared to those obtained from other human
      populations. In Khoton-Mongolians, the frequency of HLA-B38, DRB1*0301,
      DQA1*0502, DQB1*0201 and DPB1*0401 were significantly higher than those in other
      Mongoloid populations including Khalkh-Mongolians, Buryat, Chinese, Northern Han,
      Southern Han, Koreans and Japanese. In contrast, the frequency of HLA-A2,
      DQA1*0102, DPB1*0201 and DPB1*0501 were significantly lower in Khoton-Mongolians.
      Haplotype frequency analysis revealed that Khoton-Mongolians shared the same
      haplotypes specific to Mongoloids as well as to Caucasoids. On the other hand,
      several haplotypes were found to be specific for the Khoton. The phylogenetic
      tree analysis constructed by the NJ method based on allele frequencies of HLA-A, 
      B, -DRB1, -DQA1, and -DQB1 genes revealed that the Khoton belong to the Northeast
      Asian cluster and are most closely related to the Khalkh, Inner Mongolian, Uygur
      and Buryat populations. These data suggest a unique genetic background for Khoton
      Mongolians. Furthermore, they are closely related genetically to both Mongoloids
      and Caucasoids.

PMID- 9271823
TI  - Evaluation of trophoblast HLA-G antigen with a specific monoclonal antibody.
AB  - A monoclonal antibody to HLA-G has been generated by immunizing HLA-A2.1/human
      beta 2-microglobulin (beta 2 m) double transgenic mice with murine L cells
      transfected with both human beta 2 m and HLA-G. This monoclonal antibody,
      designated as G233, has been found not to cross-react with other HLA class I
      antigens when tested on numerous cell lines by flow cytometry. With
      immunohistology, all populations of extravillous trophoblast (cell columns,
      interstitial trophoblast, endovascular trophoblast, placental bed giant cells)
      were stained. An extensive range of adult and fetal tissues was also tested but
      none reacted with monoclonal antibody G233, including those previously reported
      to express HLA-G mRNA, indicating that the protein has a highly restricted
      distribution. Failure to detect HLA-G in the fetal thymus raises the question as
      to how T-cell tolerance to this antigen is induced. Immunoprecipitation of
      trophoblast surface proteins with monoclonal antibody G233 revealed a heavy chain
      of 39 kDa and a light chain of 12 kDa, indicating that HLA-G expressed on the
      surface of trophoblast is complexed with beta 2 m. However, sequential
      immunoprecipitation with monoclonal antibody W6/32 followed by monoclonal
      antibody G233 continued to detect a residual band of 39 kDa, suggesting that
      trophoblast surface HLA-G may also occur as free heavy chains not associated with
      beta 2 m. Immunoprecipitation followed by two dimensional gel electrophoresis
      showed that monoclonal antibody G233 recognizes several isoforms of HLA-G from
      trophoblast similar to the characteristic spot array previously described for HLA
      G. This monoclonal antibody G233 will be highly useful in future experiments to
      elucidate the function of HLA-G.

PMID- 9271824
TI  - The pattern of expression of CD147/neurothelin during human T-cell ontogeny as
      defined by the monoclonal antibody 8D6.
AB  - A novel monoclonal antibody termed 8D6 was generated against the human leukemic T
      cell line Molt 13 and was found to recognize the neurothelin structure, recently
      termed CD147. UM8D6 precipitated a single band from HSB2 cells of molecular
      weight 35 kDa nonreduced and 40 kDa reduced. CD147 is broadly expressed on human
      hematopoietic cells and is expressed more intensely on thymocytes than on mature
      peripheral blood T cells. A clear distinction was found by three-color flow
      cytometry between antigen density on single positive mature thymocytes subsets
      compared with the corresponding subset from peripheral blood. The 8D6 antibody
      did not have direct effects on T-cell activation or apoptosis, and the function
      of CD147 in development and activation of T cells is not yet clear. Nevertheless,
      its highly regulated expression during T-cell differentiation and the structural
      characteristics of this antigen suggest that it has an interesting and important
      role in T-cell biology.

PMID- 9271825
TI  - Proteasome subunits, low-molecular-mass polypeptides 2 and 7 are hyperexpressed
      by target cells in autoimmune thyroid disease but not in insulin-dependent
      diabetes mellitus: implications for autoimmunity.
AB  - Autoimmune thyroid diseases (AITD) and insulin-dependent diabetes mellitus (IDDM)
      are two autoimmune syndromes of unknown etiology with common immune features. One
      is that the target cells, thyrocytes and pancreatic islet beta cells
      respectively, hyperexpress several proteins encoded in the HLA region: HLA class
      I, HLA class II and transporter associated with antigen processing (TAP-1): the
      clinical course and many aspects of the immunopathology are, however, quite
      different. Low-molecular-mass polypeptides 2 and 7 (LMP2 and LMP7) are proteasome
      subunits that increase the efficiency of endogenous antigen processing and are
      encoded in close vicinity to the TAP genes. We investigated whether LMP2 and LMP7
      are hyperexpressed in thyrocytes and islet cells in AITD and IDDM. Thyroid tissue
      from Graves' disease patients (GD, n = 8) and Hashimoto thyroiditis (HT, n = 1)
      and pancreatic tissue from IDDM patients (n = 4) as well as control tissues were
      examined by the two-color indirect immunofluorescence technique. The results
      demonstrate that, in normal glands, thyrocytes and pancreatic islet cells express
      comparable moderate to low levels of LMP2 and LMP7. In AITD and IDDM, expression
      of LMP2/7 in the endocrine cells was disparate: while in AITD glands there was
      hyperexpression of LMP2 and 7 parallel to that of HLA class I and TAP-1, in the
      islet cells of recent onset diabetic pancreases (n = 2) the level of LMP2 and 7
      expression was totally normal, including islets that were infiltrated by
      lymphocytes and hyperexpressed HLA class I and TAP-1. These observations suggest
      different mechanisms of endogenous peptides generation at the target cells in
      AITD from IDDM. Since this is a key step for the maintenance of peripheral
      tolerance, it may help to understand some of the different clinical features of
      the two autoimmune diseases.

PMID- 9271827
TI  - High-resolution HLA-DRB typing using denaturing gradient gel electrophoresis and
      direct sequencing.
AB  - High-resolution HLA-DRB typing is required for bone marrow transplantation
      between unrelated donors and recipients and also for identification of novel HLA
      DRB alleles. Here we describe a method for the unambiguous identification of HLA
      DRB alleles using the polymerase chain reaction (PCR), denaturing gradient gel
      electrophoresis (DGGE) and direct sequencing. The highly variable second exon of
      all HLA-DRB1, -DRB3, -DRB4, -DRB5, -DRB6 and -DRB7 alleles was amplified using a
      single pair of generic DRB-specific primers and alleles were separated by DGGE.
      DNA was then reamplified from plugs removed from the gel and the sequences of
      these alleles were determined using fluorescent-based sequencing and allele
      assignment software. The validity of this typing procedure was confirmed by
      identification of HLA-DRB alleles for 17 individuals previously characterized by
      PCR-SSP and/or cloning and sequencing techniques. We identified 34 different HLA
      DRB alleles in these 17 unrelated individuals. Importantly, our analysis revealed
      HLA-DRB1 alleles which had not been identified using the PCR-SSP typing
      technique. Additionally, alleles from the HLA-DRB3, -DRB4 and -DRB5 loci were
      identified. Whereas traditional HLA-DRB typing methods provide limited
      information or require the use of multiple oligonucleotide primers or probes, our
      technique provides a reliable, specific and relatively rapid way of identifying
      all HLA-DRB alleles for high-resolution tissue typing.

PMID- 9271826
TI  - Idiopathic and secondary membranous nephropathy and polymorphism at TAP1 and HLA
      DMA loci.
AB  - In a previous study on the effects of TAP1 and TAP2 gene polymorphism in kidney
      allograft recipients, we found no association between graft outcome and
      recipient/donor TAP1 and TAP2 allele polymorphism or compatibility, but we
      observed a surprising increased frequency of the TAP1*0201 allele among kidney
      recipients. This increase was restricted to patients with glomerulopathy. We now
      report on a larger cohort of 178 patients with membranous nephropathy who were
      typed for their HLA-DPB1, -DRB1, -DMA, -DMB, LMP2, LMP, TAP1 and TAP2 genes
      compared with 100 random ethnically matched and healthy unrelated individuals
      used as controls. The results show a significant increased frequency of two
      markers in membranous nephropathy patients as compared with controls: firstly the
      previously recognized increase in HLA-DR3 (59% vs 18%: Pc < 1 x 10(-9), RR =
      6.6), secondly a new association with two TAP1 amino acid variants displaying
      respectively a valine in amino acid position 333 (TAP1-Val-333) and consequently
      a glycine in position 637 (TAP1Gly-637) due to its strong linkage disequilibrium
      with Val-333. No linkage disequilibrium was found between TAP1-Val-333 and HLA
      DR3. Moreover, we also noticed a decrease of the DMA*0102 phenotype in membranous
      nephropathy patients. The other HLA-DPB, -DMB, LMP2, LMP7 and TAP2 phenotype
      frequencies were roughly similar between patients and controls. These results
      show that the TAP1-Val-333 like HLA-DR3 phenotype is positively associated with
      membranous nephropathy and that these two risk factors are not cumulative in
      membranous nephropathy pathophysiology.

PMID- 9271828
TI  - Sequencing of HLA class I genes based on the conserved diversity of the noncoding
      regions: sequencing-based typing of the HLA-A gene.
AB  - We present a sequencing-based typing strategy for the HLA-A locus that is
      generally applicable to all HLA class I genes. Sequencing-based typing is the
      method of choice for matching in unrelated bone marrow transplantation on the
      allelic level. We determined the noncoding sequences of all serological antigens
      and most of their subtypes and discovered a remarkably conserved diversity
      characterized by polymorphic sequence motifs. In this study we took advantage of
      this diversity we uncovered in the 5' flanking region, 5' untranslated region and
      in the introns 1, 2 and 3, which was related to serological families. We
      established 12 primer mixes for setting up a PCR-based template preparation. Our
      strategy is based on the separate amplification of haplotypes and therefore
      defines the cis/trans linkage of polymorphic sequence motifs. This allowed
      individual sequencing of the haplotypes in all samples heterozygous for the broad
      antigens as well as the complete analysis of the polymorphic exons 2 and 3. All
      templates included the 2nd intron which was used as a priming site for the gene
      specific 5' and 3' universal sequencing primers regardless of the amplified
      haplotypes. The independent sequencing of the haplotypes allows the application
      of the dye terminator cycle sequencing technique, which is less time-consuming
      and less-laborious than dye primer chemistry. The lack of heterozygous positions
      essentially facilitates on the one hand the data analysis and on the other hand
      the detection of new alleles. Sequencing is only required in one direction due to
      the absence of peak shift problems. The results will remain unambiguous
      regardless of a growing HLA sequence data bank since this sequencing technique
      defines the cis/trans linkage of sequence motifs in more than 95% of the cases.

PMID- 9271829
TI  - Three newly identified A*24 alleles: A*2406, A*2413 and A*2414.
AB  - Three previously unknown A24-related alleles were identified by PCR-SSO typing
      and confirmed by DNA sequencing in Australian Aboriginal populations (A*2406,
      2413) and in individuals of South American descent (A*2414). A*2406 and A*2413
      both have two adjacent (but different) nucleotide substitutions in codon 156 in
      exon 3 compared to A*2402, resulting in a single amino acid replacement in each
      allele. The South American A*2414 is apparently a hybrid between A2 and A24 with
      a segment of the A*24 sequence between codons 95 and 107 in exon 3 replaced with
      the A*02 sequence. Interallelic sequence exchange is the most likely mechanism in
      the generation of all three novel alleles. Compared to A*2402, the four amino
      acid substitutions in the A*2414 molecule would be expected to significantly
      change the shape of the peptide binding cleft, leading to selection of different
      peptide ligands. The single amino acid replacements in position 156 of the two
      Australian Aboriginal A*24 alleles may also have significant functional effects.
      In particular, Trp replacing Gln in position 156 (A*2406) is predicted to
      markedly reduce the volume of the peptide binding cleft, influence the
      interaction of HLA pockets with peptide side chains, and therefore, cause major
      changes in peptide presentation. These newly defined alleles may reflect the
      adaptive process of HLA genes to local environments.

PMID- 9271830
TI  - A simultaneous negative and positive selection method that can detect chimerism
      at a frequency of 1 per 10,000 by flow cytometry.
AB  - A three-color flow cytometric method with a simultaneous negative and positive
      selection (SNAPS) approach has been developed to detect blood chimerism using a
      FITC-conjugated recipient-specific HLA monoclonal antibody, a biotinylated donor
      specific HLA monoclonal antibody and Cy5-PE-conjugated streptavidin and a PE
      conjugated CD3 monoclonal antibody. Detection of simulated blood chimerism at a
      frequency of 0.01% was achieved by SNAPS. In contrast, by one-color flow
      cytometry methods, chimerism can be detected at only about 3-4% with the same
      donor-specific HLA monoclonal antibody. The percentages of donor CD3 cells
      detected by SNAPS are proportional to the percentages of donor CD3 cells counted.
      SNAPS method provides a fast, sensitive and reliable way to analyze trace amounts
      of donor cells in a recipient's blood.

PMID- 9271831
TI  - Identification of HLA-B*5108 using polymerase chain reaction with sequence
      specific primers or sequence-specific oligonucleotide probes and sequencing.

PMID- 9271832
TI  - Corrected nucleotide sequences for HLA-A*2901 and HLA-A*3301.

PMID- 9271833
TI  - Nomenclature for factors of the HLA system, update April 1997. WHO nomenclature
      committee for factors of the HLA system.

PMID- 9271834
TI  - A review of granulosa cell tumours and thecomas of the ovary.
AB  - This review is a retrospective study of granulosa cell tumours and thecomas
      encountered in one hospital between 1970 and 1995. There were 16 granulosa cell
      tumours and 17 thecomas. The size of the granulosa cell tumours varied from 3 to
      30 cms in diameter and no correlation was found between size and evidence of
      invasion. There was also no correlation between either mitotic counts or
      histological pattern and evidence of invasion. Evidence of oestrogen production
      was found in 11 of the sixteen granulosa cell tumours (2 with endometrial
      carcinoma and 9 with endometrial hyperplasia) and in 9 out the seventeen thecomas
      (2 with endometrial carcinoma and 7 with endometrial hyperplasia). Thecomas are
      regarded as benign tumours but granulosa cell tumours are characterised by a long
      natural history with a significant capacity to recur years after an apparent
      clinical cure. It is therefore important that patients with these tumours are
      followed up indefinitely.

PMID- 9271835
TI  - Serum testosterone, DHEAS, and prolactin levels in patients with a Bartholin's
      abscess.
AB  - This study examines Prolactin and Androgen concentrations in 15 women with a
      Bartholin's gland abscess and in 15 matched normal controls. The
      Dehydroepiandrosterone sulfate concentrations were higher in the Bartholin's
      abscess group as compared to the concentrations in the control group [7.0 +/- 3.1
      mmol/l versus 4.3 +/- 1.3 mmol/l (p < 0.05), respectively]. The Prolactin and the
      Testosterone levels did not differ statistically between the two groups.

PMID- 9271836
TI  - Human papillomavirus type 18 DNA sequences in adenocarcinoma and adenosquamous
      carcinoma of the uterine cervix.
AB  - Human papillomavirus (HPV) DNA sequences were detected by Southern blot
      hybridization and polymerase chain reaction (PCR) in 10 out of 19 patients
      (52.7%) with adenocarcinoma [15] and adenosquamous [4] carcinoma of the uterine
      cervix. HPV 18 DNA was detected in 8 of these 19 patients (42.1%), HPV 16 DNA in
      1 patient (5.3%) and HPV type X (unknown) in another (5.3%). Of the 10 HPV
      positive samples HPV 18 was found in 6 out of 6 pure adenocarcinomas (100%), and
      in 2 of 4 (50%) adenosquamous carcinomas. HPV 16 and HPV X were each detected in
      1 out of 4 (25%) adenosquamous carcinomas. The physical state of the viral DNA
      was investigated in 5 of the 10 HPV-positive cases. All the specimens from these
      5 cases showed HPV to be integrated into the host genome, except for one
      adenosquamous specimen, which showed both episomal and integrated forms of HPV
      16. Six of 8 HPV 18 DNA positive specimens were from cases of pure adenocarcinoma
      and it was found by PCR that five of these 6 specimens retained fragments of
      E6/E7, LCR/E7 and early sequence of E1 fragment (sequence: 1188-1373) but deleted
      most part of E1.

PMID- 9271838
TI  - Immunohistochemically detected HER-2/neu-expression and prognosis in endometrial
      carcinoma.
AB  - Expression of the HER-2/neu proto-oncogene product was looked for
      immunohistochemically in 222 endometrial carcinomas in a retrospective follow-up
      study. The intensity of protein expression was correlated with patient survival.
      Median follow-up time was 4.8 years. In 109 (49%) of 222 endometrial carcinomas
      there was aberrant expression of HER-2/neu. HER-2/neu-expression did not
      correlate with p53-expression and proliferation rate, as determined
      immunohistochemically by the monoclonal antibody Ki-S1. In univariate statistical
      analysis aberrant HER-2/neu expression was not predictive of adjusted survival (p
      = 0.18) and of disease-free survival (p = 0.42). In multivariate analysis HER
      2/neu-expression was not found to be an independent prognosticator (p = 0.099) as
      compared to FIGO-stage (p = 0.0001), histologic grade (p = 0.00099) and
      proliferation rate (p = 0.0013). Therefore immunohistochemically detected
      expression of HER-2/neu seems not to be a clinical prognosticator in endometrial
      cancer.

PMID- 9271837
TI  - Risk factors for primary postpartum haemorrhage. A case control study.
AB  - The objective of the study was to determine which background factors predispose
      women to primary postpartum haemorrhage (PPH) at the Obafemi Awolowo University
      Hospital. The study consisted of 101 women who developed PPH after a normal
      vaginal delivery and 107 women with normal unassisted vaginal delivery without
      PPH Both cases and controls were investigated for sociodemographic risk factors,
      medical and obstetric histories, antenatal events and labour and delivery
      outcomes. Data were abstracted from the medical and delivery records and risks
      were estimated by multivariate logistic regression. The results of the univariate
      analysis revealed a number of potential risk factors for PPH but after adjustment
      by logistic regression three factors remained significant. These were prolonged
      second and third stages of labour and non-use of oxytocics after vaginal
      delivery. Previously hypothesised risk factors for PPH such as grand multiparity,
      primigravidity and previous episodes of PPH were not significantly associated
      with PPH. We conclude that primary PPH in this population is mostly associated
      with prolonged second and third stages of labour and non use of oxytocics.
      Efforts to reduce the incidence of PPH should not only be directed at proper
      management of labour but also training and retraining of primary health care
      workers and alternative health care providers in the early referral of patients
      with prolonged labour.

PMID- 9271839
TI  - Giant malignant fibrous histiocytoma of the uterus.
AB  - A case of giant (32 Kg) malignant fibrous histiocytoma (MFH) arising from the
      uterus and occupying the entire abdomen and the pelvis is reported. The patient
      had debulking surgery, followed by combination chemotherapy, but died 7 months
      after diagnosis.

PMID- 9271841
TI  - Exocervical pregnancy.
AB  - A case of cervical pregnancy with implantation of the fertilized ovum on the
      exocervix is described. This pregnancy was mistaken for an endometriotic lesion
      and treated by simple surgical excision. Discussion is centered on etiology,
      predisposing factors and management.

PMID- 9271840
TI  - Intrauterine candidiasis in a twin pregnancy after myomectomy, in vitro
      fertilization and embryo transfer.
AB  - A IVF twin pregnancy in a patient who had previously undergone a myomectomy ended
      in a intrauterine infection, placental abruption and fetal losses at 21 weeks.
      Intrauterine Candidiasis may have played a role in the pathogenesis of the
      unsuccessful outcome.

PMID- 9271842
TI  - Pregnancy after myocardial infarction and a coronary artery bypass graft.
AB  - The authors report a pregnancy in a 34 year old patient who previously
      experienced a myocardial infarction. The pregnancy ended at 39 weeks in the birth
      of a healthy girl weighting 3040 g, by cesarean section under epidural
      anesthesia. A review of the literature revealed 33 similar cases, 16 of which
      were adequately documented.

PMID- 9271843
TI  - Escherichia coli defects caused by null mutations in dnaK and dnaJ genes.
AB  - Escherichia coli dnaJ and dnaKdnaJ mutants are defective in cell growth and
      survival at high temperature. Lack of DnaK and DnaJ proteins results in cell
      filamentation and leads to the defect in motility. Synthesis of DNA and protein
      is inhibited at 42 degrees C, especially in double-deletion mutant. Degradation
      of protein was observed in both mutants at high temperature. Complementation of
      these defects can be achieved by the expression of the wild-type alleles from low
      copy number plasmid.

PMID- 9271844
TI  - Structure of cell envelope components of the primary and secondary forms of
      Xenorhabdus luminescens.
AB  - Muropeptide analysis of muramidase-digested murein (peptidoglycan) did not reveal
      any differences between the primary and secondary forms of Xenorhabdus
      luminescens. Similarly, no significant differences were found in the overall
      protein composition of the cytoplasmic and outer membranes of both forms.

PMID- 9271845
TI  - Cell wall analysis in Aspergillus niger strains characterized by different
      tolerance to toxic compounds of beet molasses.
AB  - Aspergillus niger strains, sensitive or resistant to toxic compounds of beet
      molasses, were the object of the present studies. Between the studied strains
      differences existed in the cell wall dry mass and wall components content, chitin
      synthesis, activity of enzymes involved in cell wall synthesis, and in the wall
      ultrastructure. Higher content of proteins and lipids but lower of glucan and
      chitin; less or lack of fibrillar components, thinner cell wall as well as lower
      level of glucanase and chitinase, diminished [3H] glucosamine incorporation into
      cytoplasm and cell wall characterized the sensitive strains of A. niger.

PMID- 9271846
TI  - A study of purified pyorubrin produced by local Pseudomonas aeruginosa.
AB  - A study of more than one thousand strains of local P. aeruginosa was performed.
      These include the strains production of various pigments, methods of extraction
      and purification, the pigments activity and characteristics. Lately, we have
      reported a comprehensive study about the purified blue pyocyanine pigment. This
      paper displays a parallel study of a number of physical and chemical properties
      of the purified pink pigment, the pyorubrin, that is produced by our local
      collection of P. aeruginosa strains. This characteristics is useful for
      production of an active pigment purpose and is necessary in the pigment use as
      antibiotic, in addition of importance in developing the methods of strains
      identification. Such studies are important due to the biological significance of
      pyorubrin activity against other bacteria and in comparison with some known
      antibiotics; stability tests and MIC (minimum inhibitory concentration)
      measurements indicate that found isolates were of animal and food origin mainly.

PMID- 9271848
TI  - High-glutathione containing yeast Saccharomyces cerevisiae: optimization of
      production.
AB  - Experimental design procedure was used to search for optimal medium composition
      for maximization of glutathione yield using a high-glutathione containing yeast
      S. cerevisiae S-8H. The effects of the chosen factors (glucose, peptone, KN2PO4,
      biotin and cysteine) on the relationship between yeast biomass formation and the
      content of intracellular glutathione were examined. Results obtained showed that
      glucose and peptone had significant first- and second-order effects, as well as
      different interactive effects on these overall parameters. On the other hand,
      cysteine showed only second-order effect for glutathione content and interactive
      effects for both glutathione content and yield. Its presence had a marked
      positive effect on the content of glutathione, but reduced the biomass formation.
      The optimal levels of these factors found were in the range of 2.5%, 4%, 0.027%,
      10 micrograms/cm3 and 0.08%, respectively. The average yield obtained at this
      optimium was 160.1 mg glutathione/dm3 and a glutathione content of 17 mg/g dry
      biomass.

PMID- 9271847
TI  - Bacterial growth and virulence factors production by different Bordetella
      pertussis strains.
AB  - The aim of this study was to compare bacteria growth and pertussis antigens
      (pertussis toxin-PT, filamentous haemagglutinin-FHA and endotoxin-LPS) production
      by 11 Bordetella pertussis strains. A synthetic Stainer-Scholte culture medium
      supplemented with (2,6-0-dimethyl) beta-cyclodextrin (heptakis) or
      methylcellulose (for greater PT and FHA production) and solid modified Cohen
      Wheeler medium (for LPS isolation) were used. Our results demonstrated that
      heptakis and methylcellulose were more effective for antigens production than for
      bacterial growth. It was interesting that these stimulated substances supported
      the bacterial growth from small inocula. The investigated strains differed in PT,
      FHA and LPS production. The best PT producer was the B. pertussis 134 strain, the
      worst B. pertussis 2897. The differences in FHA production are not as big as in
      PT production, but the B. pertussis 2897 was also the worst FHA producer.
      Isolated LPS consists of dry bacteria pellet ranging from 1,9% (B.p. Tohama) to
      5,6% (B.p. 3803 strain). No great differences in serological activity of LPS
      isolated from different strains were observed. In the haemagglutination
      inhibition test the endotoxin isolated from B.p. 509 and B.p. Tohama strains
      showed the highest activity.

PMID- 9271849
TI  - Replication fork arrest and termination of chromosome replication in Bacillus
      subtilis.
AB  - Sporulation in Bacillus subtilis provided the first evidence for the presence of
      sequence-specific replication fork arrest (Ter) sites in the terminus region of
      the bacterial chromosome. These sites, when complexed with the replication
      terminator protein (RTP), block movement of a replication fork in a polar manner.
      The Ter sites are organized into two opposed groups which force the approaching
      forks to meet and fuse within a restricted terminus region. While the precise
      advantage provided to the cell through the presence of the so-called replication
      fork trap is not patently obvious, the same situation appears to have evolved
      independently in Escherichia coli. The molecular mechanism by which the RTP-Ter
      complex of B. subtilis (or the analogous but apparently unrelated complex in E.
      coli) functions is currently unresolved and subject to intense investigation.
      Replication fork arrest in B. subtilis, requiring RTP, also occurs under
      conditions of the stringent response at so-called STer sites that lie close to
      and on both sides of oriC. These sites are yet to be identified and
      characterized. How they are induced to function under stringent conditions is of
      considerable interest, and could provide vital clues about the mechanism of fork
      arrest by RTP-terminator complexes in general.

PMID- 9271850
TI  - Typing Tuber melanosporum and Chinese black truffle species by molecular markers.
AB  - Morphologically similar species such as Chinese black truffles and Tuber
      melanosporum were typed by restriction length polymorphism of internal
      transcribed spacers. This analysis together with sequence comparison revealed the
      presence of high genetic variability among fruit bodies collected in China.
      Selection of primer pairs allowed the internal transcribed spacer region of both
      Chinese truffles and T. melanosporum to be specifically amplified.

PMID- 9271851
TI  - Lif, the lysostaphin immunity factor, complements FemB in staphylococcal
      peptidoglycan interpeptide bridge formation.
AB  - The formation of the Staphylococcus aureus peptidoglycan pentaglycine
      interpeptide chain needs FemA and FemB for the incorporation of glycines Gly2
      Gly3, and Gly4-Gly5, respectively. The lysostaphin immunity factor Lif was able
      to complement FemB, as could be shown by serine incorporation and by an increase
      in lysostaphin resistance in the wild-type as well as in a femB mutant. However,
      Lif could not substitute for FemA in femA or in femAB-null mutants. Methicillin
      resistance, which is dependent on functional FemA and FemB, was not complemented
      by Lif, suggesting that serine-substituted side chains are a lesser substrate for
      penicillin-binding protein PBP2' in methicillin resistance.

PMID- 9271852
TI  - Melanization affects susceptibility of Cryptococcus neoformans to heat and cold.
AB  - Cryptococcus neoformans can synthesize melanin from a variety of substrates,
      including L-dopa (L-3,4-dihydroxyphenylalanine). Growth in minimal medium with L
      dopa resulted in progressive accumulation of melanin in stationary phase cells.
      Melanized and non-melanized yeast cells were exposed to heat (42-47 degrees C)
      and cold (-20 degrees C), and the percentage of survival determined. Melanized
      cells were less susceptible to heat than non-melanized cells of the same age.
      Melanized cells from early stationary phase cultures were less susceptible to
      cold than non-melanized cells of the same age. However, melanized cells from late
      stationary phase cultures were more susceptible to cold than non-melanized cells
      of the same age. There was no statistical difference in susceptibility to heat
      and cold between melanin-deficient cells grown with and without L-dopa. These
      results suggest a role for melanin in protection against heat and cold.

PMID- 9271853
TI  - Selection and partial characterization of a Pseudomonas aeruginosa mono
      rhamnolipid deficient mutant.
AB  - Pseudomonas aeruginosa produces rhamnolipids which are tenso-active compounds
      with potential industrial and environmental applications. There are two main
      types of rhamnolipids produced in liquid cultures, rhamnosyl-beta-hydroxydecanoyl
      beta-hydroxydecanoate (mono-rhamnolipid) and rhamnosyl-rhamnosyl-beta
      hydroxydecanoyl-beta-hydroxyd ecanoate (di-rhamnolipid). In this work we report
      the selective isolation of a rhamnolipid deficient mutant (IBT8), which does not
      accumulate mono-rhamnolipid while still producing di-rhamnolipid. IBT8 was
      selected after random mutagenesis with Tn501; yet, its mono-rhamnolipid
      deficiency was found associated neither with its Tn501 insertion nor with a
      possible alteration in the rhlABRI genes for rhamnosyl-transferase 1 synthesis.
      Different possibilities to explain IBT8 phenotype are discussed.

PMID- 9271854
TI  - Homogeneity of Borrelia japonica and heterogeneity of Borrelia afzelii and
      'Borrelia tanukii' isolated in Japan, determined from ospC gene sequences.
AB  - Borrelia afzelii, B. japonica, and 'B. tanukii' isolated from various sources and
      geographical origins in Japan were characterized by restriction fragment length
      polymorphism (RFLP) analysis and sequencing analysis of the outer surface protein
      C (OspC) amplicon. B. afzelii and 'B. tanukii' generated variable RFLP patterns
      and differences in ospC gene sequence were confirmed. In contrast, 26 isolates of
      B. japonica generated one OspC RFLP type, and sequence similarity between B.
      japonica ranged from 96.4 to 99.7%. These finding suggests that B. japonica is
      unique in comparison with other members of B. burgdorferi sensu lato species with
      respect to homogeneity of the ospC gene.

PMID- 9271855
TI  - Antibacterial and hemolytic activities of linenscin OC2, a hydrophobic substance
      produced by Brevibacterium linens OC2.
AB  - Linenscin OC2 is an antibacterial substance produced by the orange cheese
      coryneform bacterium Brevibacterium linens OC2. It inhibits the growth of Gram
      positive bacteria but it is inactive against Gram-negative bacteria. The intact
      outer membrane of Gram-negative bacteria was shown to be an effective
      permeability barrier against linenscin OC2. At high dosage the effect of
      linenscin OC2 was bacteriolytic on Listeria innocua. Bacteriostasis was observed
      at low dosage and peptidoglycan biosynthesis was affected at an early step
      upstream of the UDP-N-acetylglucosamine. Hemolytic activity of this substance on
      sheep erythrocytes suggested a common mode of action on prokaryotic and
      eukaryotic cells. It also suggested that the cytoplasmic membrane might be the
      primary target of linenscin OC2.

PMID- 9271856
TI  - Structural analysis of the Trichodesmium nitrogenase iron protein: implications
      for aerobic nitrogen fixation activity.
AB  - Trichodesmium spp. are marine filamentous nitrogen-fixing cyanobacteria which
      play an important role in the nitrogen budget of the open ocean. Trichodesmium is
      unique in that it is nonheterocystous and fixes nitrogen during the day, while
      evolving oxygen through photosynthesis, even though nitrogenase is sensitive to
      oxygen inactivation. The sequence of the gene encoding the Fe protein component
      of nitrogenase from the recently cultivated isolate Trichodesmium sp. IMS 101 was
      used to construct a 3-dimensional model of the Fe protein, by comparison to the X
      ray crystallographic structure of the Fe protein of the gamma-proteobacterium
      Azotobacter vinelandii. The primary differences in amino acid sequences of the Fe
      protein from diverse organisms do not impact the critical structural features of
      the Fe protein. It can be concluded that aerobic nitrogen fixation in
      Trichodesmium spp. is not facilitated by unique structural features of
      Trichodesmium Fe protein.

PMID- 9271857
TI  - Specific in vivo thiol-labeling of the FhuA outer membrane ferrichrome transport
      protein of Escherichia coli K-12: evidence for a disulfide bridge in the
      predicted gating loop.
AB  - The multifunctional FhuA protein of Escherichia coli K-12 forms a channel that is
      closed by a loop, tentatively designated the 'gating loop', which is also the
      principal binding site for all FhuA ligands. In this report, it is shown by in
      vivo labeling that the two cysteines in the gating loop form a disulfide bridge,
      and they react weakly after reduction with biotin-maleimide, as determined by
      streptavidin-beta-galactosidase bound to biotin. The two cysteines close to the C
      terminus of FhuA also form a disulfide bridge and react with the thiol reagents
      only after heat denaturation of FhuA in SDS. Replacement of the existing
      cysteines by serine did not alter the sensitivity of cells to the FhuA ligands
      tested (T5, phi 80, T1, colicin M, and albomycin) and supported growth on
      ferrichrome as sole iron source. The cysteines in the gating loop play no
      specific functional role; they are largely buried in the interior of the loop,
      and the disulfide bridges are not essential for maintaining the conformation of
      FhuA. The C-terminal cysteines are in the interior of FhuA and are also not
      important for the structure of FhuA. The method used allows the identification of
      free cysteines and disulfides in surface exposed protein regions.

PMID- 9271858
TI  - Identification and characterization of an aadB gene cassette at a secondary site
      in a plasmid from Acinetobacter.
AB  - Transformation studies showed that an aminoglycoside resistance gene, aadB, is
      carried on a 6.0-kb plasmid (pRAY) in a clinical isolate of Acinetobacter (strain
      SUN). The gene was cloned and sequenced. An analysis of the DNA sequencing data
      showed that although the aadB gene is part of cassette, it is not associated with
      an integron. Rather, the aadB cassette has recombined at a secondary site
      downstream of putative promoters on pRAY.

PMID- 9271859
TI  - Effects of various types of Triton X on the susceptibilities of methicillin
      resistant staphylococci to oxacillin.
AB  - We examined the effect of six types of the nonionic detergent Triton X on the
      susceptibilities of methicillin-resistant staphylococci to oxacillin. We used
      five methicillin-resistant Staphylococcus aureus isolates and 17 methicillin
      resistant coagulase-negative staphylococci isolates. All strains of S. aureus, S.
      epidermidis and S. sciuri had enhanced susceptibility to oxacillin following
      exposure to the types of Triton X having 7-13 polymerized ethylene oxides. These
      strains were altered from homogeneously resistant to heterogeneously resistant by
      Triton X-100. Those types of Triton X that affected the resistance level also
      promoted the release of lipoteichoic acid. These results and those of previous
      studies suggest that Triton X might act on factors other than the mecA or femA
      products.

PMID- 9271861
TI  - A thermal denaturation study of macronuclear chromatin in Blepharisma japonicum
      (Protozoa, Ciliophora, Heterotrichida).
AB  - The macronuclear chromatin of the ciliate Blepharisma japonicum, in two
      starvation states, was studied by thermal denaturation analysis. The behaviour of
      B. japonicum chromatin, native and reconstituted with Tetrahymena pyriformis H1
      histone, was analysed. The data obtained are consistent with the hypothesis that
      B. japonicum macronuclear chromatin contains a H1-like peptide associated with
      the linker DNA, although this peptide is reduced in amount and/or chromatin
      stabilising ability when compared to Tetrahymena macronuclear H1.

PMID- 9271860
TI  - Oxacillin-hydrolyzing beta-lactamase involved in resistance to imipenem in
      Acinetobacter baumannii.
AB  - Acinetobacter baumannii strain A148, a clinical isolate resistant to imipenem
      (MIC = 32 mg l-1), synthesized two beta-lactamases with pIs 6.3 and > 9.2. The pI
      6.3 enzyme hydrolyzed the penicillins, including isoxazoylpenicillins, first-,
      second- and, to a lesser extent, third-generation cephalosporins. It was
      inhibited by chloride ions and by the penem beta-lactamase inhibitor BRL 42715.
      Clavulanate was a weak inhibitor and EDTA did not affect the beta-lactamase
      activity. This enzyme also hydrolyzed imipenem with a catalytic efficiency
      (Kcat/Km) of 1500 mM-1 s-1. Moreover, this purified beta-lactamase produced a
      positive microbiological clover-leaf test with imipenem. Therefore, the pI 6.3
      beta-lactamase was considered to be involved in the imipenem resistance of A.
      baumannii strain A148.

PMID- 9271862
TI  - Degradation of human subendothelial extracellular matrix by proteinase-secreting
      Candida albicans.
AB  - Candida albicans infections in severely immunocompromized patients are not
      confined to mucosal surfaces; instead the fungus can invade through epithelial
      and endothelial layers into the bloodstream and spread to other organs, causing
      disseminated infections with often fatal outcome. We investigated whether
      secretion of the C. albicans acid proteinase facilitates invasion into deeper
      tissues by degrading the subendothelial basement membrane. After cultivation
      under conditions that induce the secretion of the acid proteinase, C. albicans
      degraded radioactively metabolically labeled extracellular matrix proteins from a
      human endothelial cell line. The degradation was inhibited in the presence of
      pepstatin A, an inhibitor of acid proteinases. Pepstatin A-sensitive degradation
      of the soluble and immobilized extracellular matrix proteins fibronectin and
      laminin by proteinase-producing C. albicans was also detected, whereas no
      degradation was observed when the expression of the acid proteinase was
      repressed. Our results demonstrate that the C. albicans acid proteinase degrades
      human subendothelial extracellular matrix; this may be of importance in the
      penetration of C. albicans into circulation and deep organs.

PMID- 9271863
TI  - Fluviols, bicyclic nitrogen-rich antibiotics produced by Pseudomonas fluorescens.
AB  - Fifteen fluorescent pseudomonads, isolated from the rhizosphere of agricultural
      plants, were similar in both their phenotypic properties and the chemical nature
      of produced pigments, to the previously described Pseudomonas fluorescens var.
      pseudoiodinum. DNA-DNA hybridisation data showed their genetic similarity (but
      not identity) to different biovars of P. fluorescens. A family of antibiotics
      fluviols belonging to pyrazolo-[4,3-e]as-triazine derivatives was isolated from
      studied strains; isolation, properties, antimicrobial and antitumour activity of
      fluviols are described.

PMID- 9271864
TI  - High-efficiency transposon mutagenesis by electroporation of a Pseudomonas
      fluorescens strain.
AB  - A method is described for mutagenesis of Pseudomonas fluorescens strains by
      electroporation with the transposon delivery vector pUT/mini-Tn5 Km. The
      transposition process was shown to be optimal at 12.5 kV cm-1 for a pulse time
      (Bowen and Koslak, 1992) of about 4 ms. The Pseudomonas fluorescens L6.5 target
      strain exhibited maximal electrocompetence when harvested at the middle of the
      exponential growth phase. As many as 7.7 10(5) mutants per picomole of delivery
      vector (7.5 kb) could be obtained, and these kanamycin-resistant mutants were
      shown to have lost the pUT plasmid. By external calibration with plasmids of
      increasing size (from 11.5 to 60.1 kb), the efficiency of the transformation
      process was evaluated to be approximately 1.31 x 10(8) transformants per picomole
      of delivery vector. Efficiency of the transposition process was 0.58%. This rapid
      method was used to tag for the cloning three independent chromosomal loci
      responsible for the Alk+ phenotype of Pseudomonas fluorescens L6.5 strain.

PMID- 9271865
TI  - Disruption of a sigma factor gene, sigF, affects an intermediate stage of spore
      pigment production in Streptomyces aureofaciens.
AB  - The Streptomyces aureofaciens sigF gene encodes a sigma factor. By integrative
      transformation, via double cross-over, a stable null mutant of sigF gene was
      obtained. This mutation appeared to have no obvious effect on vegetative growth,
      but affected the late stage of spore maturation. Microscopic examination showed
      that spores were deformed, and spore wall was thinner, compared with the wild
      type spores. The spore pigment of sigF mutant was green, compared to wild-type
      grey-pink spore pigmentation. The plasmid-born wild-type sigF gene complemented
      the mutation after transformation of the mutant strain.

PMID- 9271866
TI  - Identification of a Streptococcus suis 60-kDa heat-shock protein using western
      blotting.
AB  - This study was initiated to investigate the presence of stress or heat shock
      proteins in Streptococcus suis. SDS-PAGE and Western blotting using polyclonal
      and monoclonal antibodies directed against different bacterial heat shock
      proteins demonstrated cross-reactivity with a protein with an apparent molecular
      mass of 60 kDa in all S. suis serotypes tested. The 60-kDa cross-reactive protein
      was present in virulent and avirulent strains of S. suis serotype 2 tested. A
      rabbit antiserum raised against the 60-kDa S. suis protein recognized the 60-65
      kDa heat shock proteins in different Gram-positive and Gram-negative bacteria.
      Finally, the 60-kDa heat shock protein of S. suis was shown to be mostly secreted
      into the culture supernatant and, to a lesser extent, cell-associated. Growth
      under heat stress conditions (42 degrees C) increased the expression of the 60
      kDa S. suis protein. This protein is, to our knowledge, the first common antigen
      found in different serotypes of S. suis.

PMID- 9271868
TI  - The hydrophilic C-terminal part of the lambda S holin is non-essential for
      intermolecular interactions.
AB  - Available evidence indicates that oligomerization of the bacteriophage lambda S
      holin leads to a non-specific lesion in the cytoplasmic membrane which permits
      transit of the phage encoded transglycosylase to the periplasm. In an attempt to
      locate an intermolecular interaction domain in S a chimeric protein comprising
      the N-terminal 32 aa of phage PhiX174 lysis protein E and the last 75 aa of
      lambda S has been constructed. We report that the E phi S fusion protein is
      stable, membrane bound, and inhibits S-mediated lysis in trans. C-terminal
      truncations of the E phi S fusion protein indicated that the hydrophilic C
      terminal end of S (i.e. the last 15 aa) is non-essential for oligomerization.

PMID- 9271867
TI  - Expression of small RNAs by Bacillus sp. strain PS3 and B. subtilis cells during
      sporulation.
AB  - A small RNA sequence identified in an rRNA-tRNA cluster from the thermophilic
      Bacillus sp. strain PS3 was examined. An oligonucleotide probe specific for the
      RNA bound to multiple restriction fragments in Bacillus sp. strain PS3 DNA, thus
      several copies of this sequence occur in its genome. Similar findings were
      observed using DNA from B. subtilis, B. stearothermophilus, Escherichia coli,
      Staphylococcus aureus, Haemophilus influenzae and Thermus thermophilus. This
      sequence apparently is widespread in the eubacteria. Northern analysis of RNA
      from sporulating Bacillus sp. strain PS3 and B. subtilis cells revealed RNA
      species homologous to the probe in both bacteria. Expression of the small RNA in
      B. subtilis depended on sigma H.

PMID- 9271869
TI  - The NAD synthetase NadE (OutB) of Bacillus subtilis is a sigma B-dependent
      general stress protein.
AB  - The identification of sigma B-dependent general stress proteins is a useful
      strategy to understand the physiological role of the unspecific stress response
      in Bacillus subtilis. By N-terminal sequencing of B. subtilis stress proteins
      Gsp38 was identified as the NAD-synthetase (NadE). NadE was previously
      characterized as spore outgrowth factor B (OutB) conferring a temperature
      sensitive spore outgrowth defective phenotype. Transcriptional studies showed
      that nadE is strongly induced in response to heat, ethanol and salt stress or
      after starvation for glucose in a sigma B-dependent manner. Two promoters are
      involved in transcriptional initiation, the sigma A-dependent upstream promoter
      contributes to the basal level during growth, whereas the sigma B-dependent
      downstream promoter is induced after different stress conditions.

PMID- 9271870
TI  - Biosynthesis of poly(4-hydroxybutyric acid) by recombinant strains of Escherichia
      coli.
AB  - The aim of this study was the production of the homopolyester poly(4
      hydroxybutyric acid) (poly(4HB)) with recombinant strains of Escherichia coli.
      Wild-type strains and other widely used non-recombinant strains of E. coli are
      not able to produce polyhydroxyalkanoic acids (PHA) as storage compounds and
      cannot utilize 4-hydroxybutyric acid as sole carbon source. Accordingly, hybrid
      plasmids of pBluescript vectors were constructed which harbored the Alcaligenes
      eutrophus PHA synthase gene (phaC) and the Clostridium kluyveri orfZ putatively
      encoding a 4-hydroxybutyric acid-coenzyme A transferase. A 3.5-kb genomic
      SmaI/ApaI fragment from A. eutrophus, which comprises phaC, and a 1.8-kb genomic
      ApaI/EcoRI fragment from C kluyveri, which contained orfZ, were inserted into the
      SmaI and EcoRI sites of the vectors pKS- and pSK-, respectively. The two
      resulting plasmids pSKSE5.3 and pKSSE5.3 comprising phaC and orfZ colinear or
      antilinear to lacZ, respectively, were transformed into E. coli XL1-Blue.
      Recombinant strains synthesized the homopolyester poly(4HB), when the cells were
      cultivated in Luria-Bertani broth and if glucose and 4-hydroxybutyric acid were
      provided as carbon sources. If glucose was omitted, a copolyester of 3
      hydroxybutyric acid and 4-hydroxybutyric acid was accumulated. The homopolyester
      poly(4HB) was also accumulated during cultivation of these strains in M9 mineral
      salts medium containing glucose plus 4-hydroxybutyric acid as carbon sources.
      Poly(4HB) could amount up to approximately 80% (w/w) of the cell dry matter if E.
      coli XL1-Blue harboring pKSSE5.3 was cultivated in M9 mineral salts medium and if
      the cultures were not sufficiently supplied with oxygen. 4HB was also
      incorporated into PHA if gamma-butyrolactone was used as carbon source. If
      levulinic acid, 4-hydroxyvaleric acid or gamma-valerolactone were used as carbon
      sources, only very low amounts of PHA were accumulated which did not contain 4
      hydroxyalkanoic acids as constituents.

PMID- 9271871
TI  - Marginal cross-resistance to mosquitocidal Bacillus thuringiensis strains in
      Cry11A-resistant larvae: presence of Cry11A-like toxins in these strains.
AB  - Culex quinquefasciatus mosquito larvae resistant to the Cry11A toxin showed
      marginal cross-resistance to the multiple toxin crystals from B. thuringiensis
      subsp. israelensis and also to toxin crystals from three other mosquitocidal
      strains, i.e. B. thuringiensis subsp. fukuokaensis, subsp. jegathesan, and subsp.
      kyushuensis. Cross-resistance patterns of the Cry11A-resistant larvae to
      mosquitocidal strains of B. thuringiensis together with the immunological
      screening using antisera raised against Cry11A indicated the presence of Cry11A
      like toxins in these strains and could be used as a screening tool for the
      identification of novel toxins. The Cry11A-resistant larvae had significantly
      less resistance to the Cry11B toxin from B. thuringiensis subsp. jegathesan. The
      occurrence of cytolytic toxins in all of these mosquitocidal strains partially
      explains the marginal cross-resistance observed with multiple toxin crystals
      since each of these crystals also contains cytolytic toxins.

PMID- 9271872
TI  - Molecular characterization of a flagellar/chemotaxis operon in the spirochete
      Borrelia burgdorferi.
AB  - A chemotaxis gene cluster from Borrelia burgdorferi, the spirochete that causes
      Lyme disease, was cloned, sequenced, and analyzed. This cluster contained three
      chemotaxis gene homologs (cheA, cheW and cheY) and an open reading frame we
      identified as cheX. Although the major functional domains for B. burgdorferi CheW
      and CheY were well conserved, the size of cheW was significantly different from
      the homolog of other bacteria. Phylogenetic analysis of CheY indicated that B.
      burgdorferi constitutes a distinct branch with Treponema pallidum and is closely
      associated with Archea and Gram-positive bacteria. RT-PCR analysis indicated that
      the chemotaxis genes and the upstream flagellar gene flaA constitute an operon.
      Western blot analysis using antibody to Escherichia coli CheA resulted in two
      reactive proteins in the cell lysates of B. burgdorferi that is consistent with
      two cheA homologs being present in this organism. The results taken together
      suggest both similarities and differences in the chemotaxis apparatus of B.
      burgdorferi compared to those of other bacteria.

PMID- 9271874
TI  - Development of a technique for multiple site-directed mutagenesis of the ftf gene
      of Streptococcus salivarius containing palindromic sequences.
AB  - Attempts at site-directed mutagenesis of the fructosyltransferase (ftf) gene of
      Streptococcus salivarius ATCC 25975 using standard protocols were unsuccessful
      and resulted in a series of deletions. These deletions appeared to commence at
      points within the ftf gene where there were palindromic sequences which were
      capable of forming closed loop structures that acted as terminators under the
      conditions of mutagenesis. To overcome this problem, two modified mutagenic
      techniques were developed. They made use of T4 DNA polymerase in conjunction with
      either T7 DNA polymerase at 37 degrees C or Vent DNA polymerase from Thermococcus
      litoralis at an elevated temperature. These methods eliminated the need for a
      single-stranded DNA template and allowed polymerisation through palindromic
      sequences to rapidly produce multiple site-directed mutations.

PMID- 9271873
TI  - The N-terminal half part of the oral streptococcal antigen I/IIf contains two
      distinct binding domains.
AB  - In order to investigate the binding properties of the antigen I/IIf from
      Streptococcus mutans, we analyzed the binding activity of five I/IIf derivatives
      expressed by I/IIf gene derivatives obtained by insertion of a kanamycin
      resistance marker. ELISA-derived binding assays showed that the derivatives
      containing both the N-terminal alanine-rich domain (A-region) and an A-region
      distal domain extending to amino-acid 766 were the most effective in binding
      biotinylated (Biot-) human salivary components (SAC) and Biot-epithelial cell
      membrane components. Sodium metaperiodate treatment of SAC inhibited these
      interactions, suggesting a binding specificity of the A-region distal domain for
      carbohydrate residues. All the I/IIf derivatives were found to bind Biot-type I
      collagen, Biot-laminin, Biot-keratin, and Biot-fibronectin, the derivatives
      containing the A-region but lacking the A-region distal domain exhibiting the
      highest binding levels. Sodium metaperiodate treatment of laminin had no effect
      on its binding to the derivatives, suggesting that carbohydrate residues of the
      ligand were not involved.

PMID- 9271875
TI  - Inhibition of in vitro growth of enteropathogens by new Lactobacillus isolates of
      human intestinal origin.
AB  - Three human Lactobacillus strains, coded B21060, B21070 and B21190, have recently
      been isolated. The strains show a series of features (acid and bile resistance,
      adhesion to various types of mucosal cell) which make them particularly promising
      for the preparation of probiotic products. In the present study, the ability of
      the strains to inhibit the growth of pathogens in coculture was investigated.
      Lactobacilli were incubated simultaneously or after one overnight growth with
      enterotoxigenic Escherichia coli, Salmonella enteritidis or Vibrio cholerae.
      After 24 and 48 h, bacterial counts of the pathogens and of the lactobacilli were
      performed. The results showed that these Lactobacillus strains inhibited the in
      vitro growth of E. coli and S. enteritidis under both conditions. Moreover, a
      cumulative effect was observed for mixtures of lactobacilli. In contrast, no
      significant inhibition of Vibrio cholerae growth was observed, provided that the
      pH of the medium was kept constant. The presence of the pathogens did not affect
      the growth of the Lactobacillus strains. Moreover, each of the Lactobacillus
      strains showed coaggregation ability with two pathogenic E. coli strains, namely
      ATCC 25922 and ATCC 35401.

PMID- 9271877
TI  - Phenolic substrates for fluorometric detection of laccase activity.
AB  - A fluorometric procedure has been developed for detection and estimation of
      laccase activity in fungal broth cultures. Laccase solution was pretreated with
      catalase for 1 h at 37 degrees C and pH 5. Homovanillic acid was then added and
      the reaction mixture incubated for a further hour at 37 degrees C. The
      fluorescence was then developed by addition of 0.1 M glycine buffer at pH 10.
      Laccase preparations from Pyricularia oryzae, Coriolus hirsutus and Pycnoporus
      cinnabarinus catalysed formation of a fluorescent product of HVA but the optimum
      pH values of enzyme activities varied. The culture fluids of several other fungi
      also catalysed development of fluorescence in solutions containing HVA. p
      Hydroxyphenylacetic acid was a poor substrate for all laccases in vivo except
      that produced by Perennipora tephropora.

PMID- 9271878
TI  - Cyclosporiasis in North America associated with fruit and vegetables.

PMID- 9271876
TI  - Colorimetric protein phosphatase inhibition assay of laboratory strains and
      natural blooms of cyanobacteria: comparisons with high-performance liquid
      chromatographic analysis for microcystins.
AB  - Microcystins are cyclic heptapeptide hepatotoxins commonly produced by bloom
      forming genera of cyanobacteria. These toxins are potent and specific inhibitors
      of protein phosphatases 1 and 2A. We have optimised a rapid, simple and sensitive
      colorimetric protein phosphatase 1 inhibition assay, utilising the activity of
      protein phosphatase 1 as expressed in a recombinant strain of Escherichia coli,
      towards the chromogenic substrate, p-nitrophenyl phosphate. A standard curve for
      the inhibition of protein phosphatase 1 by microcystin-LR was constructed with an
      IC50 of about 38 ng ml-1 and a limit of detection of 10-20 ng ml-1. Twenty-three
      laboratory-grown strains and 25 natural bloom samples of cyanobacteria were
      analysed by high-performance liquid chromatography for microcystins and by the
      protein phosphatase 1 inhibition assay. Agreement for the microcystin contents of
      the samples detected by high-performance liquid chromatography and the protein
      phosphatase 1 inhibition assay showed good correlation (R2 > 0.93, P < 0.0001).
      The suitability of the colorimetric protein phosphatase 1 inhibition assay as a
      screen for cyanobacterial microcystins is discussed.

PMID- 9271879
TI  - Changing expectations.

PMID- 9271881
TI  - Mutuality--an expression of nursing presence.
AB  - Nursing exists in the details of relationships. One crucial element of
      therapeutic nurse-patient/parent relationships is the attribute of mutuality.
      Mutuality not only embodies the philosophy of family-centered-care, it
      acknowledges and supports the evolution of parents and nurses toward greater
      competency in their role. Using concept analysis, this article explores the
      phenomenon of mutuality. The desired outcome is to provide a theoretical and
      operational definition of mutuality that will help guide practice and direct
      future research in the area of therapeutic nurse-parent relationships.

PMID- 9271880
TI  - Determining research priorities in pediatric nursing: a Delphi study.
AB  - A two-round Delphi study was performed in Pediatric Nursing at a large midwestern
      teaching hospital. The purpose of the study was to identify research priorities
      for the Pediatric Research committee for future projects. The initial survey was
      sent to all pediatric nursing staff. Sixty-two staff (19%) responded to the first
      round. Forty-five separate research topics/themes of interest were identified.
      The second round survey was sent to the 62 staff who responded to Round 1. Forty
      eight staff (76%) responded. Participants were given a list of the 45 topics
      identified in Round 1, and asked to identify their top five priorities. Results
      were analyzed by unit and by Division. The identified priorities for the Division
      are described here.

PMID- 9271882
TI  - Nurses' practices and perceptions of family-centered care.
AB  - This exploratory, descriptive study examined pediatric nurses' perceptions and
      practices of family-centered care. Nurses (n = 124) indicated on the 55-item
      Family-Centered Care Questionnaire (FCCQ) whether the activity was necessary for
      family-centered care and was currently a part of their practice. Content
      validity, test-retest reliability, and internal consistency were good. The nurses
      perceived that they performed all elements significantly less in their current
      practice than they believed necessary. Their perceptions about the necessary
      components and their practices of family-centered care varied with their age and
      clinical position. Although nurses indicated knowledge of family-centered care,
      they reported that they did not incorporate this knowledge into their practice.
      Several issues, such as nurses' ability to practice family-centered care, the
      support of the hospital infrastructure provided for nurses to practice family
      centered care, and nurses' perceptions of their role in caring for families, help
      to explain the findings.

PMID- 9271883
TI  - Ethnic differences in adolescents' perceived health status: preliminary findings.
AB  - The purpose of this exploratory study was to identify ethnic differences in the
      perceived health status among three ethnic groups of adolescents. Significant
      differences were found for perceived health as measured by the General Health
      Rating Index (GHRI) [R2, 94) = 8.11, p = .0006]. Tukey's post hoc analysis showed
      that European American and Latino American subjects scored higher on the GHRI
      than African Americans. These preliminary findings have implications for further
      research on perceived health status among ethnically diverse populations of
      adolescents.

PMID- 9271884
TI  - Adolescent mothering: child-grandmother attachment.
AB  - This study explored the involvement of maternal grandmothers with children of
      adolescent mothers and child-grandmother attachment. In a sample of 32 children
      whose grandmothers were involved in child care, 44% were securely attached to
      mothers and 72% securely attached to grandmothers. Of the 18 children insecurely
      attached to mothers, 82.4% were securely attached to grandmothers. A significant
      relationship existed between attachment security and the time the child was with
      grandmother, sleeping time excluded. In contrast, time with mother was not
      related. Based on attachment theory, findings are presented and implications for
      nursing practice are made.

PMID- 9271885
TI  - Glycogen storage disease: a basic understanding and guide to nursing care.
AB  - Glycogen storage disease (GSD) is a group of genetic metabolic disorders
      resulting from a defect in the synthesis or degradation of glycogen. GSDs are
      classified according to the type of enzymatic defect and primary organs involved
      and are usually diagnosed in infancy or early childhood. Little is generally
      known about GSD and nurses may be unfamiliar with care requirements of the GSD
      patient. Nine distinct types of GSD are presented with the primary focus on type
      1, the most common. Current treatment methods, roles of the nurse, and a sample
      nursing care plan are included.

PMID- 9271886
TI  - Preparation of children for surgery and invasive procedures: milestones on the
      way to success.
AB  - The cost of a preparation program is relatively low, but its value for the
      subject undergoing treatment is very high. Feelings of satisfaction and
      contentment usually accompany the preparation process, and are mutual. Therefore,
      it is highly recommended to make the necessary efforts to develop preparation
      programs and to implement them regularly and systematically. It is probable that
      a preparation program that allows for the special characteristics of each child
      and family, that is accompanied by diverse demonstration aids, and that stresses
      a love for children and counseling, as well as cooperation between all the agents
      involved ... should in most cases be a successful one.

PMID- 9271888
TI  - Cultural competence: a critical factor in child health policy.

PMID- 9271887
TI  - Preparing children for same day surgery: innovative approaches.

PMID- 9271889
TI  - Nutrition assessment in children with sickle cell disease.
AB  - Children with sickle cell disease have decreased height and weight when compared
      with their peers. Although exact reasons for poor growth have not been
      established, increased calorie and protein needs and deficiencies in zinc, folic
      acid, and vitamins A, C, and E may be factors. To determine whether inadequate
      nutrient intake contributes to this poor growth, we conducted a survey of the
      nutrition knowledge and practices of families affected by sickle cell disease.
      Sixty-one patients with a median age of 8 years (range, 13 months to 17 years)
      participated in the study. Patients with homozygous S hemoglobin (sickle cell)
      disease (Hb SS, n = 34) and sickle beta zero thalassemia (Hb S beta zero
      thalassemia, n = 2) were combined; 19% were below the fifth percentile for
      height. The other patients, with sickle hemoglobin C disease (Hb SC, n = 21) and
      sickle beta plus thalassemia (Hb beta(+)-thalassemia, n = 4), were grouped, and
      4% were below the fifth percentile for height (P = .043). Ninety percent of the
      study patients or their parents were familiar with the food groups indicated on
      the US Department of Agriculture's Food Guide Pyramid, but most patients failed
      to consume appropriate amounts from those groups. Although two thirds of the
      patients ate the recommended number of servings daily from the meat group, only
      20% to 31% of the recommended servings from each of the other food groups was
      consumed. This was possibly related to low socioeconomic status. The patients in
      the Hb SS group ate significantly less from the bread (P < .037) and milk (P <
      .022) categories than the patients in the Hb SC group. Fifty-nine percent of
      families had incomes below the poverty level, and 79% participated in a food
      assistance program. We conclude that the nutrient intake of patients with sickle
      cell disease is often inadequate. Education for patients with sickle cell disease
      should focus on (1) specific nutrient needs, with proper distribution of dietary
      intake among the food groups, (2) ways to provide nutritious meals on a limited
      income, and (3) methods for increasing calorie and protein intake.

PMID- 9271890
TI  - Overt malignancy in long-term hemodialysis patients.
AB  - We studied all 39 patients who were on maintenance hemodialysis for 10 years or
      more (range, 10 to 24 years) in three free-standing, not-for-profit hemodialysis
      units to determine the prevalence of malignancy. The three dialysis units have a
      total patient population of 470, all of whom are cared for by the same group of
      physicians. From the same dialysis units, we selected a control cohort of 37
      patients matched for age, gender, race, and renal diagnosis who were on
      hemodialysis for 3 years or less (short-term patients). Control patients were
      selected by randomly choosing the next patient who filled the criteria for
      duration of dialysis from the roster of all patients at a facility. Clinically
      overt malignancy during dialytic therapy was determined by history, physical
      examination, Pap smear, mammogram, and colonoscopy in patients with
      gastrointestinal bleeding. The mean age (+/-SE) of the long-term patients was
      51.8 +/- 1.9 years, and that of the control group was 51.5 +/- 2.4 years (P =
      .92). Thrice-weekly hemodialysis prescriptions were similar in both groups: long
      term, 3.5 +/- 0.02 hours; control, 3.4 +/- 0.02 hours (P = .27). No malignancy
      was detected in either the long-term or the short-term patients, and no patient
      of either group had a malignancy in the past. Colonic biopsy specimens of four
      long-term patients who had gastrointestinal bleeding were normal. The prevalence
      of malignancy was not increased in patients who were on maintenance hemodialysis
      for 10 years or longer.

PMID- 9271891
TI  - Hyperleukocytosis with pertussis.
AB  - A 9-month-old nonimmunized white female patient presented with a paroxysmal cough
      and a white blood cell count of 114,000/mm3. A nasopharyngeal culture was
      positive for Bordetella pertussis. Hyperleukocytosis is a rare complication of
      pertussis and is attributed to lymphocytosis-promoting factor. Hyperleukocytosis
      with pulmonary leukostasis can result in significant hypoxemia, although it did
      not occur in the case presented.

PMID- 9271892
TI  - Massive nerve root hypertrophy in chronic inflammatory demyelinating
      polyradiculoneuropathy.
AB  - In the course of investigating severe, shooting leg pains in a patient with
      chronic inflammatory demyelinating polyradiculoneuropathy, we observed massive
      nerve root enlargement on magnetic resonance imaging. Clinical evaluation ruled
      out other possible etiologies. Lumbar laminectomy was performed in an attempt to
      alleviate the pain, with poor results. A review of the literature revealed that
      seven similar cases have been reported in the past. We report another case and a
      review of the literature.

PMID- 9271893
TI  - Seasonal synchronicity and stage-specific life cycles: Topp's beetles revisited.
AB  - In his study on Catops nigricans (Coleoptera: Leiodidae), Topp (W. Topp,
      Selection for an optimal monovoltine life-cycle in an unpredictable environment:
      Studies on the beetle C. nigricans Spence. Oecologia 84: 134-141 (1990).)
      observed that the times of eclosion and oviposition of a population of this
      European beetle are tightly synchronized to the local seasonal environment. Topp
      proposed that the key mechanism producing such synchrony is the developmental
      response that individuals exhibit to seasonal fluctuations of temperature and
      light at discrete stages of their life cycle. Here, an individual-level model of
      the C. nigricans life cycle is constructed and parameterized with the complete
      set of Topp's stage-specific development data. Seasonal variations of temperature
      and light are replicated by sinusoidal functions of time. Simulations are carried
      out to investigate the temporal behavior of lineages (generated from an arbitrary
      cohort) exposed to these periodic environmental variations over several
      generations. Our results support the hypothesis that stage-specific development
      in a periodic environment produces a powerful mechanism by which life-cycle
      synchronization can occur.

PMID- 9271895
TI  - Optimal harvesting from a population in a stochastic crowded environment.
AB  - We study the (Ito) stochastic differential equation [equation: see text] as a
      model for population growth in a stochastic environment with finite carrying
      capacity K > 0. Here r and alpha are constants and Bt denotes Brownian motion. If
      r > or = 0, we show that this equation has a unique strong global solution for
      all x > 0 and we study some of its properties. Then we consider the following
      problem: What harvesting strategy maximizes the expected total discounted amount
      harvested (integrated over all future times)? We formulate this as a stochastic
      control problem. Then we show that there exists a constant optimal "harvest
      trigger value" x* epsilon (0, K) such that the optimal strategy is to do nothing
      if Xt < x* and to harvest Xt-x* if Xt > x*. This leads to an optimal population
      process Xt being reflected downward at x*. We find x* explicitly.

PMID- 9271894
TI  - Analysis of a model for the pathogenesis of AIDS.
AB  - According to a previously proposed mathematical model, the pathogenesis of
      acquired immunodeficiency syndrome (AIDS) could be explained by two phenomena:
      direct human immunodeficiency virus (HIV) infection of CD4+ T-cell populations
      and ongoing generation and selection of HIV mutants with increasing replicative
      capacity. In the present paper, the results obtained with this model are
      described in more detail. For different values of biologically interpretable
      parameters, the model predicts very different patterns of CD4+ T-cell decline
      after primary infection. With the assumption of a variability of 10% to 25% of
      three parameters between infected individuals, the model yields a realistic
      distribution curve of the incubation period to AIDS.

PMID- 9271896
TI  - Infectious disease persistence when transmission varies seasonally.
AB  - The generation reproduction number, R0, is the fundamental parameter of
      population biology. Communicable disease epidemiology has adopted R0 as the
      threshold parameter, called the basic case reproduction number (or ratio). In
      deterministic models, R0 must be greater than 1 for a pathogen to persist in its
      host population. Some standard methods of estimating R0 for an endemic disease
      require measures of incidence, and the theory underpinning these estimators
      assumes that incidence is constant through time. When transmission varies
      periodically (e.g., seasonally), as it does for most pathogens, it should be
      possible to express the criterion for long-term persistence in terms of some
      average transmission (and hence incidence) rate. A priori, there are reasons to
      believe that either the arithmetic mean or the geometric mean transmission rate
      may be correct. By considering the problem in terms of the real-time growth rate
      of the population, we are able to demonstrate formally that, to a very good
      approximation, the arithmetic mean transmission rate gives the correct answer for
      a general class of infection functions. The geometric mean applies only to a
      highly restricted set of cases. The appropriate threshold parameter can be
      calculated from the average transmission rate, and we discuss ways of doing so in
      the context of an endemic vector-borne disease, canine leishmaniasis.

PMID- 9271897
TI  - Fathers of the adenovirus vaccines.

PMID- 9271898
TI  - Training for operational readiness.

PMID- 9271899
TI  - The United States Navy Medical Service Corps: the golden anniversary 1947-1997.

PMID- 9271900
TI  - Helping the helpers after the bombing in Dhahran: critical-incident stress
      services for an air rescue squadron.

PMID- 9271901
TI  - Update on the Papanicolaou smear: new issues for the 1990s.
AB  - The Papanicolaou (Pap) smear is a complex examination that has undergone
      refinement in recent years. It is now widely accepted that a false-negative rate
      of perhaps 10 to 20% is inevitable for a variety of reasons. The diagnosis of
      "atypical cells of undetermined significance" is not a benign diagnosis and is
      often followed by a more severe lesion on follow-up. The Pap smear appears to be
      an inefficient method for detecting glandular neoplasms, and clinical features
      remain the most important diagnostic clue. A Pap smear and cervical biopsy should
      correlate in 75% or more of cases. In cases of noncorrelation, a positive Pap
      smear diagnosis is supported in the vast majority of cases.

PMID- 9271902
TI  - Mycoplasma pneumoniae: a frequent cause of pneumonia among U.S. Marines in
      southern California.
AB  - From August 1993 through April 1994, U.S. Marines (98% male, median age 20 years)
      who were hospitalized with radiographically confirmed pneumonia were
      prospectively studied for evidence of acute Mycoplasma pneumoniae infection.
      Overall, 32 (36.4%) of the 88 patients with paired sera had evidence of acute
      infection by an elevated immunoglobulin M titer (22.7%), a 4-fold rise in
      immunoglobulin G titer (9.1%), a positive polymerase chain reaction result
      (11.1%), and/or a positive culture (5.8%). No specific symptoms or clinical
      findings were strong predictors of M. pneumoniae infection. Among patients with
      evidence of acute M. pneumoniae infection, admitting clinicians chose other
      pathogens as more likely etiologic agents 46.4% of the time, and over the course
      of the hospitalization, 10% of patients failed to receive appropriate
      antibiotics. These data indicate that M. pneumoniae may cause a high proportion
      of pneumonias among military personnel and should be considered in empiric
      treatment and prophylaxis.

PMID- 9271903
TI  - Chagas' disease: a search for treatment and a question--should the disease be of
      military concern?
AB  - If military forces are required to operate in areas that are endemic for Chagas'
      disease, the occupation should be of critical concern. These areas, located in
      Central and South America, are many. The matter is of particular importance
      because no suitable drug exists to treat individuals who contract the disease. We
      examined 60 compounds of a chemical class, thiosemicarbazones, known to have some
      activity against the disease. The work was carried out using Trypanosoma cruzi
      infected mice. Of the 60 potential drugs evaluated, 12 showed significant
      suppressive activity. One of these compounds was almost 50% greater than the
      reference drug used in the test system.

PMID- 9271904
TI  - A proposal for the training of regional medical experts.

PMID- 9271905
TI  - Identifying the physical demands of Army Reserve personnel during deployable
      medical systems training.
AB  - The purpose of this investigation was to (1) assess the physical demands of
      soldiers involved in Deployable Medical Systems (DEPMEDS) activities, and (2)
      evaluate the incidence of musculoskeletal injuries among reserve military
      personnel involved in these tasks. The primary study group consisted of 190
      soldiers participating in a 2-week annual field training exercise. Information
      regarding the DEPMEDS construction was obtained by performance of an ergonomic
      analysis, administration of a physical exertion questionnaire, and collection of
      injury data reported during daily sick call. The neck, shoulders, and low back
      were the most frequently reported sites of musculoskeletal injury. Soldiers
      involved in DEPMEDS construction were 7.6 times more likely to sustain a
      musculoskeletal injury than soldiers not involved in this aspect of the field
      training exercise. Current methods of DEPMEDS construction that utilize medical
      personnel for erecting and dismantling equipment may reduce the unit's mission
      readiness.

PMID- 9271906
TI  - Marketing: applications in a military health care setting.
AB  - Military health care leaders must recognize the importance of satisfied
      consumers. As part of this recognition, the focus of military medicine must
      change from a coercive-power to a reward-power system. This change highlights the
      need for business practices such as marketing. Encouraging military health care
      administrators to learn and understand the applications of the marketing
      variables will enhance demand management and health care delivery for
      beneficiaries. This paper describes some applications of marketing variables,
      informs the military health care administrator about the process of marketing,
      and describes the utility of marketing in the current paradigm shift in military
      health care delivery.

PMID- 9271907
TI  - Skin disease in British troops in the Bosnian winter.
AB  - During the winter of 1995-1996, there took place a major deployment of North
      Atlantic Treaty Organization peacekeeping forces to Bosnia. Epidemiological
      surveillance of British troops through the ARRC-97 program has provided detailed
      information about their dermatological health. Skin disease was responsible for
      12.7% of primary care consultations. Dry skin prove a common problem for troops.
      We recommend that emollients be placed on general issue during winter deployments
      to the Balkans. Dermatology should be included in pre-Bosnia training for all
      medical personnel.

PMID- 9271908
TI  - A roentgen centennial legacy: the first use of the X-ray by the U.S. military in
      the Spanish-American War.
AB  - The year 1996 marked the centennial of the advent of the roentgen ray in the
      United States. The compelling value of this novel scientific discovery by
      Professor Wilhelm Roentgen of Wurzberg, Germany, to image the previously arcane
      depths of the living human body was astounding and recognized as a major advance.
      This report details the work of some key personnel and developments in the
      science of warfare that confirmed the great promise of the X-ray in the
      diagnostic armamentarium of military surgeons (a leading proponent being
      Professor Nicholas Senn, the founder of the Association of Military Surgeons of
      the United States) in this last American conflict of the 19th century.

PMID- 9271909
TI  - Long-term intravenous tocolytic therapy.
AB  - Eighteen women required continuous intravenous tocolytic therapy with either
      ritodrine hydrochloride or magnesium sulfate for greater than 48 hours because of
      repetitively recurrent preterm labor; these were compared with a similar group of
      women successfully treated in less than 48 hours in a retrospective, case
      controlled study. The mean gestational age at the time of diagnosis was 31 weeks
      for both groups. Tocolytic selection was similar in both groups, although the
      dosage per hour was significantly greater with long-term therapy. The mean
      interval from initiation of therapy until delivery was 41 days in the study
      group, compared with 39 days among controls (not statistically significant). The
      mean gestational age at delivery was 36 weeks in both groups. There were no
      significant difference in various measures of fetal outcome between groups. These
      data demonstrate that long-term intravenous tocolytic therapy can be a safe and
      effective means of prolonging gestation in those women who fail to respond to
      conventional treatment.

PMID- 9271910
TI  - The clinical detection of scleral icterus: observations of multiple examiners.
AB  - Sixty-two medical observers at various levels of medical training examined six
      patients for the presence or absence of scleral icterus in a double-blind survey.
      At a total serum bilirubin of 42.8 mmol/l (2.5 mg/dl) and 53.0 mmol/l (3.1
      mg/dl), 58% (95% confidence interval [CI] 33-80%) and 68% (95% CI 46-85%) of
      examiners detected the presence of scleral icterus, respectively. Level of
      training appeared to influence specificity, as 6 of 8 apparent false-positives
      (total serum bilirubin = 12.0 mmol/l [0.7 mg/dl] and the presence of scleral
      icterus) were attributable to medical students. Level of training did not appear
      to influence sensitivity, as 3 of 11 apparent false-negatives (total serum
      bilirubin = 66.7 mmol/l [3.9 mg/dl] and the absence of detection of scleral
      icterus) were not attributable to medical students (p = 0.278). Even at the often
      quoted estimate of 42.8 mmol/l (2.5 mg/dl) at which at scleral icterus is
      detected, approximately one-third of medical examiners in our study did not
      detect scleral icterus.

PMID- 9271911
TI  - The history of the Army weight standards.
AB  - Medical officers in the U.S. Army are tasked with screening, evaluating, and
      processing soldiers in accordance with AR 600-9, the Army's height and weight
      standards regulation. This essay traces the origins of the Army's weight
      standards to the present day. The Army's height and weight standards have varied
      markedly, from the crude subjective assessment of selective service candidates at
      the local draft examination boards at the turn of the century to the modern,
      highly accurate methods currently used in anthropomorphic research. The
      strictness of military recruitment and retention standards closely paralleled
      changing military personnel requirements in any particular era. Racial
      integration and the influx of women into the ranks had noteworthy effects on this
      history. The evolution of the Army's weight-control program and screening
      standards reflects advancements in medical knowledge and technology, societal and
      political pressure, and the empirical tests of world wars.

PMID- 9271913
TI  - Acute dissecting aortic aneurysm in an operational environment.
AB  - Acute dissecting thoracic aortic aneurysm is a rare cause of chest pain in young
      adults. Patients require prompt surgical treatment to reduce the high risk of
      early mortality. This report describes the case of a young Army officer who
      developed a dissecting aortic aneurysm in Mogadishu, Somalia, during Operation
      Continue Hope. Moving the patient from an isolated hostile country to a location
      where definitive surgical treatment could be quickly performed presented a
      significant challenge. Military physicians who may be deployed to isolated
      locations should be familiar with this unusual cause of chest pain and be
      prepared to rapidly evacuate patients to facilities that can treat them.

PMID- 9271912
TI  - Application of United States advance directives on Italian soil.
AB  - United States medical facilities located overseas must comply with American laws
      and the laws that govern the host nation. The Patient Self-Determination Act of
      1990 is in direct conflict with Italian law. Honoring the advance directives of
      American patients on Italian soil constitutes a criminal offense for the
      physician, who is subject to 15 years of imprisonment. In response to issues
      identified in this case report, hospital staff have taken proactive steps to
      improve the management of dying patients overseas by establishing clearer
      hospital instructions education, and training and by better managing the
      psychosocial concerns of family and staff.

PMID- 9271914
TI  - Use of the hand-held dental X-ray machine during joint operation, NATO exercise
      Display Determination-92.
AB  - The hand-held dental X-ray machine is a 30-pound, battery-powered X-ray machine
      capable of use in military medicine, humanitarian missions, and training
      exercises. The machine was developed for dental radiology, but with the
      attachment of a medical collimator, the equipment can also be used for medical
      exams. In 1992, the machine was tested under field conditions in a NATO joint
      exercise in Bolayir, Turkey. The hand-held dental X-ray machine was found easier
      to use than the currently deployed Siemens dental X-ray unit and than produced
      radiographs of equal quality.

PMID- 9271915
TI  - Persistent vegetative state: clinical and ethical issues.
AB  - Coma, vegetative state, lock-in syndrome and akinetic mutism are defined.
      Vegetative state is a state with no evidence of awareness of self or environment
      and showing cycles of sleep and wakefulness. PVS is an operational definition
      including time as a variable. PVS is a vegetative state that has endured or
      continued for at least one month. PVS can be diagnosed with a reasonable amount
      of medical certainty; however, the diagnosis of PVS must be kept separate from
      the outcome. The patient outcome can be predicted based on etiology and age.
      Using outcome probabilities and etiology as criteria, patients can be subdivided
      in 5 groups and reasonable management guidelines can be suggested. Three levels
      of care can be provided to PVS patients: high technology, supportive and
      compassionate care. Pragmatic options for the various subgroups of patients are
      suggested. Management decisions will remain difficult for both the family and the
      health-care team. The role of the physician in these difficult cases is to share
      the decision-making with the family.

PMID- 9271916
TI  - From "The ethical treatment of patients in a persistent vegetative state" to a
      philosophical reflection on contemporary medicine.
AB  - The reflections put forward in this text concern the clinical and practical
      difficulties posed by the existence of patients in PVS, and the essential ethical
      issues raised, combining these ethical questions with practical and theoretical
      experience. Section 1 presents the methodology of the ethical reflection as we
      see it. Section 2 describes the clinical condition of patients in PVS. Section 3
      develops the ethical difficulties relative to PVS from the French point of view.
      Section 4 illustrates the relevance of debating the ethical significance of such
      problematic situations, whilst defending a practical position based on a
      philosophical conviction. Section 5 points out the limits of ethical reflection
      in a biomedical context, and calls for reflection closer to the source of the
      problems described. For a comprehensive appraisal of biomedical rationality, the
      final section suggests combining the bioethical debates with traditional
      philosophical ethical reflection so as to get a clearer understanding of the
      real, if limited, relevance of these debates.

PMID- 9271917
TI  - Persistent vegetative state: a presumption to treat.
AB  - The article briefly analyzes the concept of a person, arguing that personhood
      does not coincide with the actual enjoyment of certain intellectual capacities,
      but is coextensive with the embodiment of a human individual. Since in PVS
      patients we can observe a human individual functioning as a whole, we must
      conclude that these patients are still human persons, even if in a condition of
      extreme impairment. It is then argued that some forms of minimal treatment may
      not be futile for these patients; they may constitute a form of respect for their
      human dignity and benefit these patients, even if they are not aware of that.
      Moreover, it is important to consider the symbolic significance of care: while
      many believe that PVS is a kind of imprisonment, for others providing food and
      fluids is the only way to testify our proximity to these persons. The best policy
      would be to provide, as a general rule, artificial nutrition and hydration to PVS
      patients: this treatment could be withdrawn, after a period of observation and
      reflection by the family and proxies, on the basis of the proxies' objection to
      the continuation or of the patient's advance directives specifically referring to
      this situation.

PMID- 9271919
TI  - Ireland and its health service.

PMID- 9271918
TI  - Advance directives outside the USA: are they the best solution everywhere?
AB  - This article evaluates the potential role of advance directives outside of their
      original North American context. In order to do this, the article first analyses
      the historical process which has promoted advance directives in recent years.
      Next, it brings to light certain presuppositions which have given them force:
      atomistic individualism, contractualism, consumerism and entrepreneurialism,
      pluralism, proceduralism, and "American moralism." The article next studies
      certain European cultural peculiarities which could affect advance directives:
      the importance of virtue versus rights, stoicism versus consumerist
      utilitarianism, rationalism verus empiricism, statism versus citizens'
      initiative, and justice versus autonomy. The article concludes by recognising
      that autonomy has a transcultural value, although it must be balanced with other
      principles. Advance Directives can have a function in certain cases. But it does
      not seem adequate to delegate to advance directives more and more medical
      decisions, and to make them more binding everyday. It is indispensable to develop
      other decision-making criteria.

PMID- 9271920
TI  - Excellence through education.

PMID- 9271921
TI  - Vascular access: an historical review.

PMID- 9271922
TI  - Campaign for health care worker safety.

PMID- 9271923
TI  - XI International Conference on AIDS. HIV update 1996: notes from Vancouver.

PMID- 9271924
TI  - Focus on infection prevention organizations.

PMID- 9271925
TI  - The Internet and the infection control professional: harnessing the hype while
      unlocking potential.

PMID- 9271928
TI  - Why are we doing what we are doing?

PMID- 9271926
TI  - Ground zero: Ebola.

PMID- 9271929
TI  - Ethics and managed care. Mastering the administration of the unforeseen.
      Interview by Jim O'Malley.

PMID- 9271930
TI  - Preparing patient care executives to manage complexity.

PMID- 9271931
TI  - The core values of patient-centered care. More than structure.

PMID- 9271932
TI  - Rapid cycle change: business models can be successful in health care.

PMID- 9271933
TI  - The nurse executive and the physician: ally or adversary?

PMID- 9271934
TI  - A nurse manager's journey to value-based strategic planning.

PMID- 9271935
TI  - The nurse executive as health policy champion.

PMID- 9271936
TI  - A humorous look at the pilgrimage to clinical automation. Notes from the field.

PMID- 9271937
TI  - Reflections on the polarities in nurse executive practice.

PMID- 9271939
TI  - Real-time executive development through "Action Learning".

PMID- 9271938
TI  - Is it design or decline? Conflicts in re-engineering.

PMID- 9271940
TI  - Contemporary career management issues for nurses. Interview by Tim Porter
      O'Grady.

PMID- 9271942
TI  - A recommitment to our fundamental work.

PMID- 9271943
TI  - Linking the pieces of performance improvement. A guest viewpoint.

PMID- 9271941
TI  - Integrating unconventional therapies--obstacles and strategies.

PMID- 9271944
TI  - Strategies for effectively managing organizational politics.

PMID- 9271945
TI  - Alternative Dispute Resolution. Facilitating new dispute resolution systems.

PMID- 9271946
TI  - Relationship-centered care: its time has come!

PMID- 9271947
TI  - Wanted: nurses as change agents.

PMID- 9271950
TI  - Where is nursing's role in promoting culturally competent care?

PMID- 9271951
TI  - Providing quality patient care.

PMID- 9271952
TI  - Ensuring protection from genetic discrimination in health insurance.

PMID- 9271953
TI  - How does hydration affect preterm labor?

PMID- 9271954
TI  - What nurses need to know.

PMID- 9271955
TI  - Preventing teen pregnancy. It's time to stop kidding around.
AB  - The challenge of breaking the cycle of teen pregnancy patterns looms like an
      almost impossible task. For many, the tragedy of teen pregnancy within our
      society represents the failure of communities and government in addressing a
      fundamental social problem that sends hundreds of thousands of citizens into
      poverty each year. The problems surrounding teen pregnancy are complex, and so
      are the solutions, according to a host of reports released during the last 18
      months. Each of these reports paints a picture of a health problem that is
      staggering in its implications and epidemic in proportion.

PMID- 9271956
TI  - Coming to terms. Electronic fetal monitoring update.

PMID- 9271957
TI  - Getting the "go ahead". Helping patients understand informed consent.

PMID- 9271958
TI  - Terminating life support. Who decides when it's okay?

PMID- 9271959
TI  - Kindred spirits.

PMID- 9271960
TI  - A new push to reduce cesareans in the United States.

PMID- 9271961
TI  - Meta-analysis of the safety of home birth.
AB  - BACKGROUND: The safety of planned home birth is controversial. This study
      examined the safety of planned home birth backed up by a modern hospital system
      compared with planned hospital birth in the Western world. METHODS: A meta
      analysis of six controlled observational studies was conducted, and the perinatal
      outcomes of 24,092 selected and primarily low-risk pregnant women were analyzed
      to measure mortality and morbidity, including Apgar scores, maternal lacerations,
      and intervention rates. Confounding was controlled through restriction, matching,
      or in the statistical analysis. RESULTS: Perinatal mortality was not
      significantly different in the two groups (OR = 0.87, 95% Ci 0.54-1.41). The
      principal difference in the outcome was a lower frequency of low Apgar scores (OR
      = 0.55; 0.41-0.74) and severe lacerations (OR = 0.67; 0.54-0.83) in the home
      birth group. Fewer medical interventions occurred in the home birth group:
      induction (statistically significant ORs in the range 0.06-0.39), augmentation
      (0.26-0.69), episiotomy (0.02-0.39), operative vaginal birth (0.03-0.42), and
      cesarean section (0.05-0.31). No maternal deaths occurred in the studies. Some
      differences may be partly due to bias. The findings regarding morbidity are
      supported by randomized clinical trials of elements of birth care relevant for
      home birth, however, and the finding relating to mortality is supported by large
      register studies comparing hospital settings of different levels of care.
      CONCLUSION: Home birth is an acceptable alternative to hospital confinement for
      selected pregnant women, and leads to reduced medical interventions.

PMID- 9271963
TI  - A randomized controlled study of birth center care versus standard maternity
      care: effects on women's health.
AB  - BACKGROUND: The safety of birth center care for low-risk women is an important
      issue, but it has not yet been studied in randomized controlled trials. Our
      purpose was to evaluate the effect of birth center care on women's health during
      pregnancy, birth, and 2 months postpartum by comparing the outcomes with those of
      women experiencing standard maternity care in the greater Stockholm area.
      METHODS: Of 1860 women, 928 were randomly allocated to birth center care and 932
      to standard antenatal, intrapartum, and postpartum care. Information about
      medical procedures and health outcomes was collected from clinical records, and a
      questionnaire was mailed to women 2 months after the birth. Analysis was by
      "intention to treat;" that is, all antenatal, intrapartum, and postpartum
      transfers were included in the birth center group. RESULTS: During pregnancy,
      birth center women made fewer visits to midwives and doctors, experienced fewer
      tests, and reported fewer health problems. No statistical difference occurred in
      hospital admissions (4.8%) compared with the control group (4.7%). During labor,
      birth center women used more alternative birth positions, had longer labors, and
      did not differ in perineal lacerations. In both groups 1.7 percent of women
      developed complications, requiring more than 7 days of hospital care after the
      birth. During the first 2 postpartum months, about 20 percent of women in both
      groups saw a doctor for similar types of health problems, and no statistical
      difference occurred in hospital readmissions, 1.4 and 0.8 percent in the birth
      center and control groups, respectively. CONCLUSION: The results suggest that
      birth center care is effective in identifying significant maternal complications
      and as safe for women as standard maternity care.

PMID- 9271964
TI  - What do women want to know after childbirth?
AB  - BACKGROUND: Postpartum women have demonstrated a variety of health care concerns.
      This study, conducted in Washington state in 1991, investigated predictors of
      primiparas' and multiparas' desire to receive more information about 18 self-care
      and baby care topics at 7 weeks postpartum in relation to prenatal class
      attendance, short postpartum hospital stay, and other variables. METHODS: Data
      from 1161 women who completed a survey were analyzed. Percentages of women
      desiring more information on each topic were calculated stratified by parity;
      mean numbers of chosen health topics were calculated in relation to prenatal
      education, length of postpartum hospitalization, maternal age, education, social
      support, and type of delivery; and association between desire for more
      information on specific topics and length of postpartum hospitalization, maternal
      age, maternal education, and social support were calculated. RESULTS: Over three
      fourths of women wanted more information on at least one topic, and the highest
      percentage wanted more information on exercise, diet, and nutrition; getting
      along with their other children; and recognizing infant illness. Primiparas and
      multiparas who desired more information were under 25 years of age and had low
      levels of social support; in addition, multiparas with unmet information needs
      had low education and short postpartum stays. Prenatal education was unrelated to
      postpartum desire for more information. CONCLUSION: Most postpartum women want
      self-care and baby care information, a need that is not completely met by
      prenatal or postpartum education. Postpartum follow-up programs with a strong
      educational component and special targeting of high-risk women may enable health
      caregivers to better address this need.

PMID- 9271965
TI  - Body image change in pregnancy: a comparison of normal weight and overweight
      primigravidas.
AB  - BACKGROUND: Body image in pregnancy has been linked to maternal and neonatal
      health. This study examined the relationship between prepregnancy body weight and
      body image change in primigravid women. METHODS: Through a self-administered,
      free-response questionnaire, 76 primigravidas of at least 30 weeks' gestation
      described their feelings about current appearance and body shape and compared
      these to prepregnancy feelings. Respondents also completed the Body Shape
      Questionnaire to measure current concern with body shape. RESULTS: Women who were
      overweight before pregnancy were more likely to have had a positive change in
      body image when they were at more than 30 weeks' gestation. Women who were normal
      weight before pregnancy were more likely to have had a negative change. Despite
      overweight women's positive changes, their body shape concerns were more negative
      than those of normal weight women. CONCLUSIONS: Our study highlights the
      relationship between social values, prepregnancy body weight, and body image
      change during pregnancy. Some women may benefit from discussing their experiences
      in a patient-centered context.

PMID- 9271966
TI  - Hospital breastfeeding policies in the Philadelphia area: a comparison with the
      ten steps to successful breastfeeding.
AB  - BACKGROUND: The purpose of this study was to describe the current status of
      hospital breastfeeding policies and practices in the southeastern Pennsylvania
      Delaware Valley and the degree to which the hospitals are implementing the
      WHO/UNICEF Ten Steps to Successful Breastfeeding. METHODS: A descriptive case
      study design was used to collect data. From 38 hospitals with maternity services
      in the Philadelphia area, maternal and child health directors, nurse managers,
      staff nurses, lactation consultants, and childbirth educators were interviewed to
      determine each hospital's policies and practices, using a questionnaire
      addressing formal and informal breastfeeding policies. Information from the
      interviews was used to compare each hospital's policies with the WHO/UNICEF Baby
      Friendly Hospital Initiative. A classification system was developed to classify
      hospitals by level of implementation for each of the Ten Steps. RESULTS: Most
      surveyed hospitals were implementing four of the steps and partially implementing
      the remaining six. Thirty-seven percent of the surveyed hospitals were classified
      as high implementers and 63 percent as partial implementers of the Ten Steps
      overall. Key issues that affect implementation of each step were identified
      through in-depth discussion of several questions. CONCLUSIONS: Areas identified
      as needing the greatest attention by hospitals were health care professional
      breastfeeding education, breastfeeding initiation, and support of the
      breastfeeding mother, particularly in the postdischarge stage.

PMID- 9271967
TI  - Expectant parents' experience with fatigue and sleep during pregnancy.
AB  - BACKGROUND: Although both expectant mothers and expectant fathers complain of
      fatigue during the last trimester of pregnancy, studies have focused exclusively
      on mothers. This pilot study examined parents' levels of morning or evening
      fatigue, number of uninterrupted sleep periods and length of sleep during the
      last trimester of pregnancy; and the relationship of sleep to parents' reports of
      fatigue. METHODS: Data were collected from 24 midwestern, nulliparous couples,
      who completed the Visual Analog Scale for Fatigue each morning and each evening
      on 4 consecutive days during the last trimester. Concurrently, the couples
      recorded sleep and wake periods in an activity diary. RESULTS: Expectant mothers
      but not expectant fathers reported increasing levels of fatigue, especially
      morning fatigue, as the pregnancy progressed. Expectant fathers and mothers did
      not differ either in the night-time mean number of minutes of sleep obtained, or
      in the mean number of night-time uninterrupted 90-minute sleep cycles obtained.
      Fatigue and sleep were not significantly related for either mothers or fathers.
      CONCLUSIONS: These findings support the multidimensional nature of fatigue and
      indicate a need for perinatal health caregivers to develop individualized
      interventions for mothers during the last trimester of pregnancy. Fathers should
      also participate in future research of factors influencing the prenatal and
      postpartum experience.

PMID- 9271968
TI  - Improving perinatal autopsy rates: who is counseling bereaved parents for autopsy
      consent?
AB  - BACKGROUND: Concern has been expressed recently about perinatal autopsy rates,
      which are often below recommended levels. Since a possible reason for the decline
      in adult autopsy rates is the person seeking permission for autopsy, a study was
      undertaken to ascertain who were seeking consent and who offered counseling for
      perinatal postmortem examinations. METHODS: A postal questionnaire survey of
      members of a support group, Stillbirths and Neonatal Death Society in South
      Australia, was conducted. RESULTS: The idea for an autopsy was initiated by a
      physician in 20 of 46 cases and by junior medical doctors, midwives, nurses, or
      social workers in 22 of 46. Women had further counseling and discussion with
      physicians in 22 cases, junior medical staff in 10, midwives or nurses in 20,
      social worker in 9, and support group member in 1. Only 33 of the 46 women
      thought that they had been counseled about the advantages of the autopsy.
      CONCLUSIONS: It is important that all health workers involved in counseling the
      bereaved mother know of the benefits and the mechanics of an autopsy so that
      consent or refusal is based on informed counseling.

PMID- 9271969
TI  - Lessons in technology diffusion: the electronic fetal monitoring experience.

PMID- 9271970
TI  - Index to current literature.

PMID- 9271971
TI  - A randomized trial of one-to-one nurse support of women in labor.
AB  - BACKGROUND: Health researchers and provider groups have recommended that women in
      labor should receive continuous professional support. The objective of our study
      was to compare the risks and benefits of one-to-one nurse labor support with
      usual intrapartum nursing care. METHODS: A randomized, controlled trial was
      conducted in a 637-bed university hospital in Montreal, Quebec, with 413
      nulliparous women who were at more than 37 weeks' gestation, carrying singletons,
      and in labor. Women with scheduled cesarean section, scheduled induction, breech
      presentation, presence of paid labor support, or cervical dilatation over 4 cm
      were excluded. One-to-one care consisted of the presence of a nurse during labor
      and birth who provided emotional support, physical comfort, and instruction for
      relaxation and coping techniques. Usual care consisted of care for two or three
      laboring women with various types of supportive activities. RESULTS: A beneficial
      trend due to one-to-one nurse support was found with a 17 percent reduction in
      risk of oxytocin stimulation (relative risk of experimental vs control = 0.83;
      95% confidence interval = 0.67, 1.04). No significant differences were found in
      overall labor durations and overall rates of total cesarean section, cesarean
      section for cephalopelvic disproportion, epidural analgesia, admission to the
      neonatal intensive care unit, instrumental vaginal delivery, and perineal trauma.
      CONCLUSIONS: The beneficial trend attributed to one-to-one nursing in reduction
      of oxytocin stimulation suggests that implementation of recommendations for
      continuous professional support by intrapartum nursing staff may be appropriate
      in North America.

PMID- 9271972
TI  - Commentary: are nurses effective providers of labor support? Should they be? Can
      they be?

PMID- 9271973
TI  - Women's views of different models of antenatal care in Victoria, Australia.
AB  - BACKGROUND: This study assessed women's views of care in pregnancy, contrasting
      the experiences and satisfaction of women using different models of care in
      Victoria, Australia. METHODS: A statewide postal survey of women who gave birth
      during a 2-week period in 1993 was carried out 6 to 7 months after birth.
      RESULTS: Of 1336 women, 62.5 percent responded, and of these, 62.4 percent rated
      their antenatal care as very good, 27.7 percent as good, 8.2 percent as mixed,
      and 1.8 percent as poor or very poor. Although social factors, obstetric factors,
      and model of care had significant associations with satisfaction in univariate
      analyses, only model of care, mother's country of birth, and medical risk
      remained significant in a multivariate analysis using logistic regression. Women
      were most likely to be satisfied when antenatal care was provided by an
      obstetrician in private practice or a birth center. When comparisons were
      restricted to options available to women without private health insurance, using
      public hospital clinics as the baseline in a multivariate analysis, women were
      significantly more likely to be satisfied with birth center care, and
      significantly less likely to be satisfied with shared care. Contributing factors
      were waiting times, staff seeming rushed, and lack of continuity of caregiver.
      CONCLUSION: The expansion of shared antenatal care has not succeeded in improving
      satisfaction with antenatal care for women in the public health care sector.

PMID- 9271974
TI  - The effect of discharge pack formula and breast pumps on breastfeeding duration
      and choice of infant feeding method.
AB  - BACKGROUND: A study of breastfeeding mothers was conducted from October 1993
      through July 1994 in the western United States to determine the influence of
      components of hospital discharge packs on the duration of breastfeeding. METHOD:
      On discharge from the hospital, over 1600 breastfeeding mothers were given one of
      four free discharge packs, identical in all ways except that one contained a can
      of powdered formula, one a manual breast pump, one both formula and pump, and one
      neither. During the following 6 months, mothers were interviewed by telephone
      three times by an independent research firm to determine how and what they were
      feeding their infants. Analysis of the independent and interactive effects of
      both formula and pump was performed, and the moderating effects of age,
      ethnicity, marital and insurance status, prebirth feeding plan, and the effect of
      returning to outside employment or school were examined. RESULTS: Across the
      entire sample, the contents of the discharge packs had a negligible effect on
      feeding method and breastfeeding duration. Examination of select subgroups
      revealed modest discharge pack effects, wherein the presence of discharge pack
      formula increased the likelihoof2p4 introducing supplementation during the first
      6 weeks whereas receipt of pumps prolonged full breastfeeding. Even in these
      select groups, however, no effect was observed on the overall duration of
      breastfeeding. CONCLUSION: Relative to other known influences on the choice of
      feeding method and on breastfeeding duration, discharge pack contents do not
      merit great concern.

PMID- 9271975
TI  - Commentary: discharge packs: how much do they matter?

PMID- 9271976
TI  - Low prenatal weight gain among low-income women: what are the risk factors?
AB  - BACKGROUND: Although a large body of evidence suggests that prenatal weight gain
      is an important determinant of fetal growth, 23 to 38 percent of nonobese women
      have low prenatal weight gain. Determination of potential risk factors for low
      gain is essential to develop targeted intervention programs. This study examined
      the association of maternal sociodemographic, lifestyle, and reproductive
      characteristics with the actual occurrence of low gain among 536 black and 270
      white low-income, nonobese women. METHODS: Sociodemographic, pregnancy
      wantedness, reproductive, and anthropometric data were obtained by interview
      during the first prenatal visit. A 72-item questionnaire, administered at 24 to
      26 weeks' gestation, assessed residential and household characteristics, housing
      characteristics, income, transportation, physical activity, employment, and
      institutional support. Variables associated with low gain in bivariate analyses
      were included in logistic regression analysis to determine the adjusted odds
      ratios for low gain. RESULTS: Three characteristics were associated with
      increased adjusted odds ratios for low prenatal weight gain among black women:
      having a mistimed or unwanted pregnancy, caring for more than one preschool child
      at home, and not using own car for errands. One characteristic, working more than
      40 hours per week when employed, was associated with low gain among white women.
      CONCLUSION: Although these preliminary findings require additional confirmation,
      they suggest that a variety of sociodemographic and lifestyle features deserve
      investigations that target the identification and characterization of risk
      factors for low prenatal weight gain.

PMID- 9271977
TI  - Depression after childbirth: the views of medical students and women compared.
AB  - BACKGROUND: Little research has been conducted on the views of health
      professionals about women's experiences of depression after childbirth. This
      study compared the views held by undergraduate medical students about postnatal
      depression with those of women who had themselves experienced it. METHODS: Fourth
      and sixth-year medical students at one Australian university were surveyed (n =
      134). Their views about prevalence, duration, contributing factors, and advice
      for dealing with postnatal depression were compared with the findings from 60
      women in a population-based study of mothers who gave birth in Victoria in 1989,
      in which women scoring as depressed 8 to 9 months after birth on the Edinburgh
      Postnatal Depression Scale were interviewed 12 to 18 months later about their
      experiences of depression and their advice to other mothers. RESULTS: Women's and
      students' views differed markedly, with students much more likely to view
      hormonal and biologic factors and a "tendency to depression" as playing an
      important role than women who identified a wide range of social, physical health,
      and life event factors as contributing to their experience of depression. Fourth
      year students tended to overestimate the prevalence of depression and sixth-year
      students to underestimate it. Both groups underestimated the duration of
      depression compared with women's actual experiences. CONCLUSION: Medical students
      need to develop a broader understanding of maternal depression after the birth of
      a baby, and women's own views of the experience can and should make an important
      contribution to medical teaching on this topic.

PMID- 9271978
TI  - Breastfeeding and the use of pacifiers.
AB  - BACKGROUND: This study was designed to test the hypothesis that incorrect sucking
      technique and pacifier use are factors contributing to breastfeeding failure.
      METHOD: The nursing patterns of 82 exclusively breastfeeding mother-infant pairs
      were observed 4 to 5 days postpartum on the maternity ward at University Hospital
      in Malmo, Sweden. The breastfeeding outcome and pacifier use was assessed by
      regular telephone contacts during a 4-month follow-up. RESULTS: The breastfeeding
      rate at 4 months was 91 percent in the nonpacifier group and 44 percent in the
      pacifier group (p = 0.03). An incorrect superficial nipple-sucking technique at
      the breast from the start combined with pacifier use resulted in early weaning in
      most cases. CONCLUSION: To promote successful breastfeeding and to reduce nursing
      problems, an incorrect sucking technique should be prevented or corrected, and
      the use of pacifiers should be avoided or restricted.

PMID- 9271979
TI  - Care in normal birth: a practical guide. Technical Working Group, World Health
      Organization.
AB  - This paper summarizes the key findings and recommendations reported by the
      Technical Working Group of the World Health Organization in the 1996 publication,
      Care in Normal Birth: A Practical Guide. The report addresses issues of care in
      normal birth irrespective of the birth setting or level of care. Its
      recommendations are based on the scientific evidence for or against some common
      obstetric practices, and are not specific to a country or region.

PMID- 9271980
TI  - Cesarean sections: women's choice for giving birth?

PMID- 9271981
TI  - Epidurals and breastfeeding.

PMID- 9271982
TI  - Lamaze and Bradley childbirth classes.

PMID- 9271983
TI  - Concerns about the institutionalization of childbirth education.

PMID- 9271984
TI  - Index to current literature.

PMID- 9271986
TI  - Day surgery--communication and interviewing skills.

PMID- 9271985
TI  - Juvenile chronic polyarthritis.

PMID- 9271987
TI  - Pre-assessment of the day surgery patient.

PMID- 9271988
TI  - Meeting the informational needs of patients in a day surgery setting--an
      exploratory level study.
AB  - This exploratory level study attempts to identify if nurses employed in a day
      surgery unit of a small district general hospital assess the individual
      informational needs of patients in their care. Data was gathered by
      questionnaire, highlighting a range of significant issues, which the report
      concludes, produces scope for future enquiry, if day surgery is to continue to
      accelerate toward projected purchasing and planning targets (DoH 1996), but
      retain a commitment to a quality assurance agenda.

PMID- 9271989
TI  - Homeostasis--the key concept to physiological control. 8. Wound healing: a series
      of homeostatic responses.

PMID- 9271990
TI  - PC heaven--Part 5. Anything is virtually possible.

PMID- 9271991
TI  - Experiences in Bosnia.

PMID- 9271992
TI  - HIV transmitted by bone graft.

PMID- 9271993
TI  - The tobacco beast fights on.

PMID- 9271994
TI  - The evolving role of nurses in clinical trials.

PMID- 9271995
TI  - Health promotion and early detection of cancer in older adults: a practical
      approach.
AB  - Little is known about the cancer-related knowledge, attitudes and health
      behaviours of older adults (> 55 years), or about designing health promotion and
      early detection interventions responsive to their learning needs. A collaborative
      project was established with the intent of designing an appropriate program for
      older adults. The initial work included a community needs assessment using focus
      groups, one-on-one interviews and self-report surveys. The use of key community
      contacts was effective in locating older adult subjects (> 55 years) through pre
      established linkages with agencies. Various ethnocultural groups, low income
      communities and isolated individuals, as well as other pre-established groups,
      were included in this study. The needs assessment found that: age is not
      perceived as a cancer risk factor; transportation is a barrier to screening; fear
      inhibits people from being screened; physicians are viewed as both the main
      source of expert cancer knowledge and as the gatekeepers to screening; family and
      peers are the main source of support, ethnospecific groups have different
      information needs; and finally, that lifestyle suggestions can reduce the risk of
      cancer. The findings indicated that community health promotion programs for older
      adults will require multiple approaches with a combination of strategies in order
      to meet their learning needs.

PMID- 9271996
TI  - The relationship between perceived social support and mood of testicular cancer
      patients.
AB  - A descriptive correlational study was conducted to investigate the relationship
      between perceived social support and mood of testicular cancer patients two to
      three months post-diagnosis. The conceptualization for the study was based on the
      cognitive-phenomenological theory of psychological stress (Lazarus and Folkman,
      1984). A convenience sample of 30 young adult males with testicular cancer was
      interviewed. Data were collected using the Demographic Data Sheet, MOS Social
      Support Survey. Importance of Social Support Questionnaire, Profile of Mood
      States and two open-ended interview questions. Data indicated subjects felt well
      supported, especially in areas that they thought were important. No significant
      relationship was found between perceived social support and mood in this sample.
      The findings suggest the need for the nurse's individualized assessment regarding
      the testicular cancer patient's number of close friends/relatives and the
      importance placed on different types of support.

PMID- 9271997
TI  - Taxol extravasation: a case report.
AB  - Taxol is a relatively new antineoplastic agent whose classification as either
      vesicant, non-vesicant, or irritant remains under debate. This case study is
      presented to follow a large-volume Taxol extravasation. The article illustrates
      assessment, follow-up, intervention and outcome of this situation. This case
      suggests the drug is a vesicant with the potential to cause moderate soft tissue
      injury.

PMID- 9271998
TI  - Distance education: the only way to go for a practising oncology nurse in the
      north.
AB  - Distance education refers to any education experience in which the instructor is
      separated from the student/learner by geographic distance (Penny, Gibbons &
      Busby, 1996). "What is new about that?", you may ask. Nothing-but it is the type
      of education which we need to provide that is new. This article is about the
      personal experiences of a nurse enrolled in the adult oncology nursing program at
      McMaster University in Hamilton, some 450 kilometers from her home. It is not the
      miles that separate you from a goal, only the commitment.

PMID- 9271999
TI  - Complementary therapies: the decision-making process of women with breast cancer.

PMID- 9272000
TI  - Clinical trial of a computer-assisted intervention for women with breast cancer:
      a study in progress.

PMID- 9272001
TI  - In profile with Marilyn Bouchard. Interview by Judith Hanson.

PMID- 9272002
TI  - Nursing research: keeping up the momentum.

PMID- 9272003
TI  - Should nursing development units be accredited?
AB  - Nursing development units (NDUs) are defined, and their achievements described,
      in this article. The advantages and disadvantages of accreditation for nursing
      development units are discussed and models of accreditation outlined. It is
      argued that the advantages of accreditation include protection for NDUs against
      changes in health policy and management. Disadvantages of the accreditation
      process include the enormous pressure placed on NDU leaders; these stressors are
      identified. Strategies implemented in South Western Sydney and Western Sydney in
      1996 to reduce NDU leadership stress are described.

PMID- 9272004
TI  - Assisted reproductive technology.

PMID- 9272005
TI  - Nursing knowledge development: where to from here?
AB  - Issues related to nursing epistemology are reviewed. This review includes
      discussion of logical positivism, empiricism and interpretive-emancipatory
      paradigms, their influence on the construction of knowledge and on its methods of
      derivation and verification. Changes in the conceptualisation of science are
      explored, and scientific realism is introduced as a contemporary philosophy of
      science through which the discipline of nursing can develop. Questions
      surrounding the development of nursing knowledge are examined; for example, the
      implications of theory construction through the use of borrowed theory and the
      acceptance of external philosophies of science. Argument is offered for and
      against borrowing external theories and philosophies, or developing theories and
      philosophies from research into nursing practice. The relationship between
      research method and the phenomenon under study is discussed. The need to develop
      a broad base of nursing knowledge through diverse research methods is addressed.
      Links are created between the development of non-practice-based theories, the
      derivation of knowledge a priori, and the poor use of nursing theory and research
      in nursing practice. It is suggested that nursing science should develop through
      a dialectic between nursing research and practice, and that such a dialectic
      could assist the forward movement of nursing through the evolution of meaningful
      nursing theories and philosophies of nursing science.

PMID- 9272006
TI  - Planning aged care in Australia: a review and critique of the reforms 1975-96.
AB  - The residential aged-care reforms implemented a decade ago in Australia have seen
      the planning of nursing-home beds, hostel places and home/community care using a
      rigid, demographically-based formula. This planning had its roots in a number of
      commissioned reports and reviews, and the aim was control over the unsustainable
      growth of the nursing-home industry and a reversal of the trend toward
      institutionalisation of the elderly. The demographic profile of the Australian
      population is changing and the profile of nursing-home and hostel residents has
      also changed. Community services appear inadequate for a continuum of care and de
      institutionalisation. Acute services have adopted a casemix-based system of
      funding, which has an effect on appropriate care of the elderly by moving more
      elderly patients out of the acute institutions into the community, hostels and
      nursing homes. Despite all these shifts, the planning ratio for nursing-home beds
      remains as set in 1986. This paper provides an overview of the federal
      government's planning of aged care in Australia from an historical perspective,
      one which identifies some of the influences that have had a bearing on the
      planning process. Further discussion centres around what is occurring in aged
      care, as related to the planning arrangements and with an emphasis on nursing
      home-based care. The present planning ratio is restrictive and has not been
      researched for appropriateness or validity on a national basis, which brings into
      question its reliability in planning for the future health-care needs of the
      elderly population. The planning of aged care can only be accomplished with any
      reliability when the many variables impinging on aged care have been clearly
      defined.

PMID- 9272007
TI  - VRE in Australia: when antibiotics fail, what then?

PMID- 9272008
TI  - Borders, boundaries and balloons: conceptual and professional issues in defining
      the scope of practice.
AB  - International approaches to defining the scope of nursing practice are many and
      varied. Some attempts to do this have produced models which are cumbersome lists
      of tasks or behaviours, or statements which do not clearly articulate the scope
      of practice. Others have provided processes for the extension of the scope of
      nursing practice without clearly identifying what is being extended. This paper
      explores relevant conceptual and professional issues which may assist nurses to
      address this important issue for nursing in Australia. These issues will be
      discussed in terms of boundaries limiting practice, borders being extended and
      balloons being flexible and shaped by forces and events internal and external to
      them.

PMID- 9272009
TI  - Healing wounds.

PMID- 9272010
TI  - Conference review--climate change and human health in the Asia-Pacific. Canberra,
      September 23-24, 1996.

PMID- 9272011
TI  - Hope: a concept for home care nursing.
AB  - Hope is an important concept to nursing. It is a powerful human response seen in
      every age group, across all demographic lines, and within all health care
      settings. Hope is a component of virtually every nurse-patient relationship
      developed in every field of nursing. Nowhere is the significance of hope more
      visible than in the home care setting. Whether it is a hospice visit or a
      postpartum follow-up visit with a new mother and infant, the home care nurse
      instinctively searches for evidence of hope in the patient and his or her support
      system. Hope has long been recognized by nurses as not only valuable but also
      essential to health.

PMID- 9272012
TI  - Quality management in home care: models for today's practice.
AB  - In less than a decade, home care providers have been a part of two major
      transitions in health care delivery. First, because of the advent of managed care
      and a shift from inpatient to community-based services, home care service
      delivery systems have experienced tremendous growth. Second, the principles and
      practices of total quality management and continuous quality improvement have
      permeated the organization, administration, and practice of home health care.
      Based on the work of Deming, Juran, and Crosby, the basic tenets of the new
      quality management philosophy involve a focus on the following five key areas:
      (1) systems and processes rather than individual performance; (2) involvement,
      collaboration, and empowerment; (3) internal and external "customers"; (4) data
      and measurement; and (5) standards, guidelines, and outcomes of care. Home care
      providers are among those in the forefront who are developing and implementing
      programs that integrate these foci into the delivery of quality home care
      services. This article provides a summary of current home care programs that
      address these five key areas of quality management philosophy and provide models
      for innovative quality management practice in home care. For further information
      about each program, readers are referred to the original reports in the home care
      and quality management journal literature, as cited herein.

PMID- 9272014
TI  - Snap judgment. What is it? Arteriovenous malformation.

PMID- 9272013
TI  - Meeting the challenge of elder mistreatment.

PMID- 9272015
TI  - Getting organized to practice home health nursing.

PMID- 9272016
TI  - Documentation and effective patient care planning.
AB  - The creation of effective home care documentation serves many important purposes.
      From a payor perspective, such as Medicare, the clinical documentation can
      provide the basis for covered care. On the other hand, poor documentation can
      raise questions about medical necessity and even eligibility criteria, such as
      the patient's homebound status. Documentation can either support payment for
      covered services or begin the cycle toward increased requests for information and
      more-focused medical review processes. The following discussion provides key
      tips, information, a comprehensive checklist, and outcomes examples that support
      the creation of "best practices" for home care organizations related to clinical
      documentation.

PMID- 9272017
TI  - Psychiatric home health: the newest kid on the block.
AB  - What is psychiatric home health care? Psychiatric home health care is a clinical
      specialty of home health services in which psychiatric nurses, social workers,
      home health aides, and occupational therapists visit the patient with a primary
      psychiatric diagnosis in the patient's own home. This service has been
      acknowledged in the Home Health Agency Manual for at least a decade but only
      recently has received widespread attention from home health providers. In fact,
      beginning in May 1996, the Health Care Financing Administration has broadened the
      service capacity by allowing all physicians, not just psychiatrists, to sign a
      Medicare psychiatric plan of care. This new standard is consistent with already
      recognized trends of primary care physicians treating psychiatric patients. The
      mental health literature is increasingly giving recognition to alternatives to
      traditional continuum of care models that favor psychiatric hospitalization.
      Addition of in-home interventions to psychiatric delivery systems has resulted in
      significant reduction in both hospitalization admission and recidivism rates. The
      models tested have, unfortunately, not used psychiatric home health care, but as
      more awareness and programs come into existence, psychiatric home health care can
      play a significant role in the mental health delivery system, particularly in a
      managed care environment.

PMID- 9272018
TI  - More than squeaky blue shoes and a black bag. Home care in a rural area.
AB  - Overall, the face of public health nursing has changed dramatically during the
      past several decades, and perhaps the most significant influence-for good or ill
      has been the advent of managed care in this specialized domain of nursing
      practice. As managed care organizations supplant physicians as the gatekeepers of
      care, deciding when, in what form, and at what cost care is provided, three major
      changes have occurred in the home care arena. These changes affect patients,
      their families, the location of their care, and the roles and responsibilities of
      the health care team. The home care landscape, regardless of geographic setting,
      has dramatically changed for all participants. In the continuing effort to reduce
      the high costs of health care, managed care companies are mandating that patients
      be discharged from the hospital earlier, shifting care to the home. In essence,
      the home has become a "step-down" unit of the hospital. Patients are being sent
      home sicker, with higher acuity levels, and at risk for increased morbidity and
      readmission rates. Families are taking on more responsibility for care provided
      in the home. In addition, the role of the visiting nurse has changed. She is now
      a member of an expanded home care team. She acts in a supervisory capacity more
      often, must contend with complex clinical problems, and often must oversee the
      use of high-tech equipment. She is no longer seen as the health care team member
      who wears squeaky blue shoes and renders all home care from the depths of her
      little black bag, similar to pulling the rabbit out of the hat. She is the leader
      of a team that includes numerous professional providers.

PMID- 9272019
TI  - Client advocacy in the home.
AB  - As the health care system in American continues to change at a rapid rate, more
      nursing care services are provided in the home. With these changes, various
      components of clinical nursing practice change and take on added dimensions in
      response to the change of venue. Client advocacy is one of those components. When
      health care moves into the home, limited resources and stretched client care
      services may divert the focus of care from client welfare to concerns about
      resource allocation. Financial considerations may rise above client needs by
      limiting the availability of services and materials. Under these circumstances,
      nurses must strive to maintain client welfare as the central focus of care. This
      column addresses the issue of client advocacy in home care and outlines specific
      actions that constitute client advocacy in home care settings.

PMID- 9272021
TI  - On accreditation of healthcare organizations. Joint Commission offers advice for
      improving standards compliance.
AB  - If your home care organization is preparing for a Joint Commission survey, you're
      probably very concerned about complying with the standards. The intent of meeting
      standards is not only to receive accreditation but also to improve patient care.
      And, as you will find, some of the standards are more difficult to comply with
      than others. This article identifies the 10 standards in patient-focused
      functions with which home care organizations had the most difficulty complying in
      1995. These are the standards for which home care organizations most often
      received scores of 3 (partial compliance), 4 (minimal compliance), and 5
      (noncompliance). The findings are from home care surveys that were conducted
      between January 1 and July 1 of 1995 in which the 1995 Accreditation Manual for
      Home Care was used. This manual will be used for surveys conducted through all of
      1996.

PMID- 9272020
TI  - Who defines quality?

PMID- 9272022
TI  - A common pain in the foot.

PMID- 9272023
TI  - Home care in China.

PMID- 9272024
TI  - A very special camp for very special kids.
AB  - "Because I'm a hemophiliac, I have always had to be protected. Camp Barnabas was
      the first place I could put that aside and do anything I wanted." This comment by
      a 9-year-old boy eloquently captures the spirit and reality of Camp Barnabas, a
      site that has had camp programs for special-needs children and their siblings for
      the past year. Camp Barnabas, located near Monett, Missouri, held its first
      summer sessions in 1994 and 1995 at a nearby camp, Kanakuk/Kanakomo. Camp
      Barnaba's founders, Paul and Cyndy Teas, were inspired by a Kanakuk/Kanakomo
      camper with cancer to create a camping experience paced and equipped for children
      with terminal or serious, chronic illnesses.

PMID- 9272025
TI  - The family receiving home care: functional health pattern assessment.
AB  - The winds of change in health care make assessment of the family more important
      than ever as a tool for health care providers seeking to assist the family move
      themselves toward high-level wellness. Limited medical care and imposed self
      responsibility for health promotion and illness prevention, which are natural
      consequences of these changes, move the locus of control for health management
      back to the family. The family's teachings, modeling, and interactions are
      greater influences than ever on the health of the patient. Gordon's functional
      health patterns provide a holistic model for assessment of the family because
      assessment data are classified under 11 headings: health perception and health
      management, nutritional-metabolic, elimination, activity and exercise, sleep and
      rest, cognition and perception, self-perception and self-concept, roles and
      relationships, sexuality and reproduction, coping and stress tolerance, and
      values and beliefs. Questions posed under each of the health patterns can be
      varied to reflect the uniqueness of the individual family as well as to inquire
      about family strengths and weaknesses in all patterns. Data using this model
      provide a comprehensive base for including the family in designing a plan of
      care.

PMID- 9272026
TI  - The suicidal patient: identifying, evaluating, and intervening.

PMID- 9272027
TI  - Assessing the informal caregiver: team member or hidden patient?

PMID- 9272028
TI  - MRSA: just what is it?

PMID- 9272029
TI  - Nurse-physician communication in home care and hospice: a physician's point of
      view.
AB  - As economic pressure continues to mount within the medical system, more and more
      patient contact is shifting away from expensive inpatient care. Initially, the
      shift in patient visits was away from the hospital and into clinics and the
      physicians offices. With the growth of capitated medical groups and prepaid care,
      not just inpatient days are declining. With efforts to control costs, the numbers
      of physician office and clinic visits are declining also.

PMID- 9272031
TI  - A sense of place for patients: living and dying.
AB  - In references to an individual, agency refers to the capacity of the individual
      for meaningful action. Protecting and nurturing patient agency is a central
      feature of nursing work. The moral ideals and aim of nursing practice reflect a
      commitment to the patient that includes the patient as central to the
      determination of what happens to her or him. Whereas we most commonly think of
      the capacity to make these determinations as autonomy, I use the term agency
      because autonomy is a complicated and contested issue within philosophy and
      ethics. In an earlier issue, I suggested that an understanding of place is
      important to ethics. This is so because different places or institutions do
      different kinds of work, have different values, endow ethical concepts with
      different meanings, are structured by different visions, and are controlled and
      influenced by different kinds of knowledge and power. All these factors work
      together to determine a person's agency within a given place or environment. For
      example, home care providers cannot act in patients' homes in the same way they
      can act in a hospital, and providers cannot act in a school the way they act in a
      hospital. At the same time, patients' power to act is constrained in the hospital
      in ways that it is not in their homes. In the following narrative of an
      experienced home care nurse, I examine the ethical concern that can result from a
      commitment to patient agency by home care providers.

PMID- 9272030
TI  - Elder abuse and neglect.
AB  - Home care providers have a professional and legal obligation to help prevent
      their elderly patients from being abused and neglected by family members and
      other home care providers. The elderly are often in a vulnerable situation
      because they depend on family members or others to help with personal care,
      housekeeping chores, and money management. A recent article in a major newspaper
      illustrates the problem. It reported that Mr. X, who was 84 years old, had been
      without food or water while he lay curled in the trunk of his car for 2 days
      before he was found by the police. When found, he reported that he saw daylight
      only when his housekeeper lifted the car trunk lid to ask him if her forgery of
      his check looked authentic. After he was rescued, he acknowledged that he was
      confused about why his housekeeper, who had befriended him, had turned on him. He
      expressed concern for her and hoped she would get a break in her sentencing. "She
      didn't kill me," he said. This situation is not that unusual. Elder abuse and
      neglect is a major public health problem in the United States, with most cases
      hidden from public scrutiny. The National center on Elder Abuse reports that
      cases of domestic abuse against the elderly increased from 117,000 in 1986 to
      241,000 in 1994, and that represented only a fraction of older Americans who were
      abused and neglected in their homes. The Center estimates that 818,000 elderly
      Americans were victims of various types of domestic abuse in 1994. They believe
      the rise in reported cases illustrates a growing pattern of violence and neglect
      among the nation's expanding elderly population.

PMID- 9272032
TI  - The baby benefit.

PMID- 9272033
TI  - American Medical Association sponsors press conference in home care.
AB  - On September 12, 1996, the American Medical Association, with an educational
      grant from Hoffmann-La Roche, sponsored a National Press Conference in New York
      City at the Millenium Broadway Hotel on Times Square. Attended by more than 40 of
      the nation's top health care correspondents from the leading magazine and
      newspapers in the country, this conference was designed to promote "The
      Revolution in Home and Outpatient Care." With an emphasis on new sites and new
      technologies, speakers from the Academy of Homecare Physicians presented a number
      of related subjects.

PMID- 9272034
TI  - Is your organization eligible for accreditation of equipment management and
      clinical respiratory services?
AB  - Organizations that are eligible for Joint Commission survey and accreditation of
      equipment management and clinical respiratory services (CRSs) often are surprised
      that they are actually providing these services. The traditional home medical
      equipment (HME) provider is a company that selects an appropriate piece of
      medical equipment for a patient, delivers the medical equipment to the patient in
      his or her home, assembles the equipment, instructs the patient about its use,
      and performs maintenance on the equipment as specified by the manufacturer and
      organization policy and procedure. These organizations are easily identified.
      However, a number of other health care providers also are involved in the
      provision of equipment to patients in their homes and, consequently, are eligible
      for equipment maintenance accreditation.

PMID- 9272035
TI  - An ethnographic assessment of an academic nursing center.
AB  - Establishment of nursing centers is one of the most important and most exciting
      trends in the profession of nursing. Nurse practitioners have been taking the
      lead in the management and staffing of nursing centers. The purpose of this study
      was to provide a description and an analysis of an academic nursing center.
      Through a series of observations and interviews, an interdisciplinary team
      investigated the history and organizational development of the center; the
      everyday delivery of services; staffing; and participants' assessment of the
      efficiency and quality of its services and recommendations for improving the
      services provided in the examined nursing center.

PMID- 9272036
TI  - Nurse practitioners: reevaluation of the need for and willingness to hire by
      nurse administrators, nurse practitioners, and physicians.
AB  - A survey of all nurse administrators and advanced practice nurses and a simple
      random sample survey of licensed physicians in Nevada were completed to
      reevaluate the perceived need for and willingness to hire nurse practitioners
      (NPs). The reevaluation was deemed necessary based on a similar survey that was
      completed by these authors in 1990. At that time significant questions were
      raised concerning the lack of understanding of the role of NPs in and their
      contribution to the health care team. The results of the study clearly indicate
      that the unique contributions of the NP to the health care team should be further
      publicized and clarified. In addition, for some physicians, a significant
      disparity continues to exist between the optimal, collaborative role and the more
      readily accepted dependent role of the NP. The family NP (FNP) continues to be
      the most desired specialty for those who hire NPs.

PMID- 9272037
TI  - An Appalachian interdisciplinary educational experience: barriers and benefits.

PMID- 9272038
TI  - Managing acute and chronic urinary incontinence. U.S. Department of Health and
      human services.
AB  - This Quick Reference Guide for Clinicians contains highlights from the Clinical
      Practice Guideline Update on Urinary Incontinence in Adults: Acute and Chronic
      Management, which was developed by a multidisciplinary panel of health care
      providers and a consumer representative. Findings and recommendations are
      presented for identification and evaluation of urinary incontinence (UI); use of
      behavioral, pharmacologic, and surgical treatment as well as supportive devices;
      long-term management of chronic intractable UI; and education of health care
      providers and the public. An algorithm is included to show the sequence of events
      related to the overall management of UI. Tables and forms are included to outline
      assessment and treatment options.

PMID- 9272039
TI  - The culture of learning. Access, retention, and mobility of minority students in
      nursing. Introduction.

PMID- 9272040
TI  - The humanistic edge: teaching and learning from the cultures of our society.

PMID- 9272041
TI  - Infusing philosophical thought into transcultural nursing understanding.

PMID- 9272042
TI  - The Academic Learning Center (ALC): building a culture for learning.

PMID- 9272043
TI  - The Nursing Academic Support Center (NASC): high visibility for an Hispanic nurse
      mentor.

PMID- 9272044
TI  - Learning to Learn* (LTL): offering the student academic behaviors that work.

PMID- 9272045
TI  - Learning to Learn (LTL) finds critical placement in a preclinical sequence.

PMID- 9272046
TI  - Infusing Learning to Learn (LTL) in a clinical nursing course.

PMID- 9272047
TI  - The male student nurse subgroup: Learning to Learn maps perinatal practice.

PMID- 9272048
TI  - Student empowerment: hearing students' voices.

PMID- 9272049
TI  - Mentoring African American students: one path to success.

PMID- 9272050
TI  - Outcomes assessment: a program imperative for supporting at-risk students.

PMID- 9272051
TI  - Measuring initial transcultural nursing retention efforts through qualitative and
      quantitative analysis.

PMID- 9272052
TI  - Phenomenology: looking at the students' lived experience.

PMID- 9272054
TI  - Institutional culture and American professional education.

PMID- 9272053
TI  - Educating faculty in the concept of educational biculturalism: a comparative
      study of sociocultural influences in nursing students' experience in school.

PMID- 9272055
TI  - The work/study experience: a phenomenological inquiry.

PMID- 9272056
TI  - Single-parent housing: one economic solution for students with children.

PMID- 9272057
TI  - Mentoring African-American college students: a dean's experience.

PMID- 9272058
TI  - Master of science in nursing curriculum development: clinical management with a
      transcultural focus.

PMID- 9272059
TI  - The master of science in nursing curriculum: integrating diversity content within
      an individual model's paradigm.
AB  - Faculty can play an integral role in both facilitating success for diverse
      student groups and promoting diversity through experiential approaches. A
      willingness to evaluate your own teaching style for cultural biases is the first
      step. Once this is done, decide on the culture-general skills as well as the
      culture-specific skills that are essential for students within your area of
      specialization. With those outcomes in mind, you can design experiences to
      develop in students the appreciation of diversity, the skills to interact in a
      diverse world, and an awareness of the many issues of diversity that exist in our
      homes, communities, workplace, and society.

PMID- 9272060
TI  - Beyond the individual paradigm: confronting social justice issues.

PMID- 9272061
TI  - Learning transcultural leadership through an MSN-level clinical experience.

PMID- 9272062
TI  - Of tugboats and transitions.

PMID- 9272063
TI  - Critical thinking: what is it?

PMID- 9272064
TI  - Occult reductionism in the discourse of theory development.

PMID- 9272065
TI  - Clarifying contributions of qualitative research findings.

PMID- 9272066
TI  - The patient-focused care journey: where patients and families guide the way.

PMID- 9272067
TI  - Intersubjective meeting in holistic caring: a Swedish perspective.
AB  - Intersubjectivity is a central notion in nursing which describes the important
      relationship between nurse and patient. The aim of this article is to analyze the
      concept of intersubjective meeting and to examine its meaning in light of
      selected works by nursing and nonnursing authors who have addressed the
      phenomenon. Intersubjective meeting is posited here as a true and meaningful
      confirming dialogue. Thus, three elements of this construct will be adduced for
      further elaboration: a true and meaningful meaning, a confirming meeting, and the
      meeting as dialogue. For caregivers to engage in such an intersubjective meeting,
      they must exercise knowledge of self and have access to care for the caregiver.

PMID- 9272068
TI  - Feeling uncomfortable: children in families with no place of their own.
AB  - The number of children living in shelters in the United States dramatically
      increased during the 1980s. Despite this increase in number, little is known
      about their experiences. The purpose of this research using Parse's method was to
      generate a structure of the lived experience of feeling uncomfortable for
      children in shelters. The investigator sought to expand nursing's knowledge base
      about feeling uncomfortable and to provide a better understanding of the
      experiences of children in families with no place of their own. The findings
      suggest that the lived experience of feeling uncomfortable for the participants
      is a disturbing uneasiness with the unsureness of aloneness with togetherness
      amidst longing for personal joyful moments. These findings, considered from
      Parse's human becoming theory, create a theoretical structure of feeling
      uncomfortable. Similarities and differences with related literature are
      discussed. Implications for practice and further research are offered.

PMID- 9272069
TI  - Testing Orem's theory of self-care deficit: dependent care agent performance for
      children.
AB  - The purpose of this study was to test Orem's theory of self-care deficit, one of
      three constituent theories included in her general self-care deficit theory of
      nursing. Specifically, the relationship between dependent care agent performance
      and basic conditioning factors was examined. Dependent care agent performance for
      children was defined as health promotion and self-care activities provided by a
      responsible adult on behalf of the child. The Dependent Care Agent Questionnaire
      was used with a sample of 380 mothers of children from ages 1 to 16 years. The
      hypothesis that basic conditioning factors influenced dependent care agent
      performance was supported (R2 = .13, p = .0001).

PMID- 9272070
TI  - Rogerian science, phantoms, and therapeutic touch: exploring potentials.
AB  - Traditional medical approaches to the treatment of potentially distressing
      phantom pain and sensations have been inconsistent in their success. In this
      article, the subject of phantom pain and sensations is explored and
      reconceptualized according to Martha Rogers' science of unitary human beings.
      Emergent perspectives, illustrated by a series of short case studies, suggest
      that such a reconceptualization and particularly the use of therapeutic touch may
      have a significant impact on positive human field image patterning.

PMID- 9272071
TI  - Quality of life and the human becoming theory: exploring discipline-specific
      contributions.
AB  - This article explores the concept of quality of life. Current understandings of
      quality of life are considered in relation to the notion of discipline
      specificity. The authors contend that different disciplines require distinct
      definitions of quality of life and that research which informs practitioners
      about quality of life needs to be discipline-specific and theory-based. The
      contribution of the human becoming theory to knowledge and understanding of
      quality of life in nursing science is explored, drawing on insights from theory
      guided practice and research.

PMID- 9272072
TI  - The meaning of alcohol to traditional Muscogee Creek Indians.
AB  - The purpose of this study was to learn the meaning of alcohol to the traditional
      Muscogee Creek Indians of eastern Oklahoma. Using Leininger's theory of culture
      care diversity and universality as the theoretical base, the authors conducted
      interviews of 24 traditional people to elicit both emic and etic meanings of
      alcohol. The conceptualization of alcohol as a dichotomy of power to do both good
      and evil emerged as the central theme. Other meanings of alcohol were explicated
      in relation to five social structure dimensions. The findings suggest culturally
      competent nursing implications for preserving, accommodating, and repatterning
      the meaning of alcohol.

PMID- 9272074
TI  - Nursing: a cultural phenomenon.

PMID- 9272073
TI  - Reality: a seamless symphony of becoming.
AB  - Health care providers worldwide are visioning anew their commitment to service
      with an emphasis on person-focused care. Receivers and providers are frustrated
      with the ineffectiveness of the machine model health care delivery systems and
      are considering different possibilities. In this article the human becoming
      perspective as a guide to multidisciplinary health care delivery is discussed in
      light of discipline-specific goals.

PMID- 9272075
TI  - The science of comforting.

PMID- 9272076
TI  - Nursing among diverse cultures. Come all peoples of the earth.

PMID- 9272077
TI  - Cross-cultural and cultural-specific tools.

PMID- 9272078
TI  - Family care givers. Windows into their worlds.

PMID- 9272079
TI  - Taiwan's aging population. Will they take their pills?

PMID- 9272080
TI  - Vietnamese and Australian birth styles.

PMID- 9272081
TI  - A cultural dilemma: Pakistani nursing.

PMID- 9272082
TI  - Nursing among diverse cultures. Rwanda's two wars.

PMID- 9272083
TI  - Native Hawaiian health.

PMID- 9272084
TI  - The "Florence Nightingale of Jamaica"--Mary Seacole, nurse pioneer.

PMID- 9272085
TI  - Health, health care and philanthropy.

PMID- 9272086
TI  - [Dialectic hermeneutics: a way of thinking in nursing research].
AB  - This paper is a theoretical study about dialectic and hermeneutics union and the
      possibility of its application as a "way of thinking" in nursing research. For
      this, we retake its origin and discussion at the present time, as well as the
      theoretical postulates that gives it foundation, looking forward on expanding the
      horizons in nursing investigation.

PMID- 9272087
TI  - [Systemic arterial hypertension: clinical aspects and aspects of care].
AB  - This article is a literature review about the concepts of systemic arterial
      hypertension, it's incidence, the diagnostic methods and used treatments. It
      emphasizing the nurse's role in the patients care, based on the authors' nursing
      practice at Hospital de Clinicas Porto Alegre. The authors describe measures to
      prevent and promote health, as well as advanced actions during hypertension
      crisis and emergency cases.

PMID- 9272088
TI  - [Treatment of materials used in laparoscopy].
AB  - The present study describes the antimicrobiological methods used for ooscopic
      instruments and also recommends a routine of material caring, methods and
      products to be employed. These orientations were also based on the author's
      experience with those methods of cleaning, disinfection and sterilization at a
      school hospital. It is expected to simplify the procedures describing its steps
      with scientific embasement.

PMID- 9272089
TI  - [Division of labor in nursing and a global view of care].
AB  - The objective of this study was evaluate the knowledge of nursing assistants
      about the patient's clinical evolution and global care in a public hospital. The
      results showed that nursing assistants do not have a global knowledge on planned
      care of patients, their clinical evolution and complications.

PMID- 9272090
TI  - [The battle for health during the social movement in Aratiba].
AB  - This article is a study about the process of fight and organization for health,
      developed in Aratiba country in RS/Brasil, on a period between 1985 and 1993. For
      this we tried to articulate theoretical discussion and empirical data, reflecting
      about the State as a conflictive space, about the dominant ideology and the
      counter-ideology mechanisms (reproduced by the social movement), the educational
      spaces originated in the interior of the social movement and the possibilities of
      citizenship construction resulting from social participation.

PMID- 9272091
TI  - [Women's experiences in the late weaning of children].
AB  - The aim of this study is to present the processes, concepts and women's
      experiences during "late" weaning process because women's experiences on natural
      weaning aren't reports in the literature. It's a qualitative study which
      methodological approach is the Grounded Theory and the data collect method is
      Participating Observation. Data about 60 women were collected through two
      techniques: open interview and non-structured observation. Late weaning occurs in
      the absence of physical, physiological or social problems and contains an
      experience of five sub-processes: "Believing in an age limit", "Skepticism in the
      feeding power of mother's milk", "Being influenced", "Weaning with tranquility"
      and "Some difficulties in weaning".

PMID- 9272092
TI  - [Freire's education model applied to a program of teaching of nursing practice].
AB  - The present study is a qualitative research supported by Paulo Freire's writings.
      It presents the structure of a discipline-Nursing Teaching Practice-which
      searches for an amplification of opportunities provided by the Nursing School in
      order to improve the student's consciousness of his/her role as a future
      educator.

PMID- 9272093
TI  - [Perceptions of nulliparous women about prematurity].
AB  - This study was made in a neonatal intensive care unit in a school hospital at
      Porto Alegre/RS, trying to identify the reactions of nuliparous mothers about
      prematurity. Ten (10) interviews with mothers of premature infants was made. The
      most commonly reactions were: fear, guilty, anxiety, negation, angry and
      depression. The mother's feeling about the team, are also observed, and
      classified in: positive (tranquility, safety, trust, regardless) and negative
      (doubt, indifference, guilty, envy and fear). A plane of nursing care was made to
      mothers of premature infants in neonatal intensive care unit (NICU), with the
      objective of humanization and improving the assistance.

PMID- 9272094
TI  - [Experiencing the integration between nursing teachers and nurses. A research
      project].
AB  - This article reports the integration experience between registered nurses and
      nurse educators in a teaching hospital. The study is a research with focus on the
      care significance to adult clients in a outpatient unit.

PMID- 9272095
TI  - Paracrine regulation of cellular interactions in the testis: factors in search of
      a function.
AB  - Throughout evolution, gamete generation and sex hormone production are the two
      processes combined in the testis. The local proximity of sex steroid-producing
      cells and spermatogenic cells allows multiple cellular interactions to occur and
      thereby facilitates the modulation and/or synchronisation of both testicular
      functions. This mini review provides an introduction to the vast variety of
      different testicular cell types, the unique bi-compartmental organization of the
      testis, the many factors being released in the testis and the different forms of
      cellular interactions occurring between testicular cells. Selected members of two
      groups of signal molecules (sex steroids, growth factors) are described in detail
      and specific examples for the intratesticular actions of signalling factors are
      presented.

PMID- 9272096
TI  - Multiple regulatory elements in the human GnRH receptor gene.

PMID- 9272097
TI  - Importance of estrogens in human males' fertility and bone pathophysiology.

PMID- 9272098
TI  - Autocrine/paracrine cell death in Hashimoto's thyroiditis.

PMID- 9272099
TI  - Reduced gastric inhibitory polypeptide but normal glucagon-like peptide 1
      response to oral glucose in postmenopausal women with impaired glucose tolerance.
AB  - OBJECTIVE: The gastrointestinal hormones, gastric inhibitory polypeptide (GIP)
      and glucagon-like peptide 1 (GLP-1), are both released from the gut after oral
      glucose ingestion and stimulate insulin secretion. This study examined the
      release of these hormones in subjects with impaired glucose tolerance (IGT),
      which precedes the development of non-insulin-dependent diabetes. DESIGN AND
      METHODS: Six postmenopausal women with IGT, aged 59 years, underwent a 75 g oral
      glucose tolerance test and plasma levels of GIP and GLP-1 were determined
      regularly during the following 2 h. The results were compared with those in seven
      age- and weight-matched women with normal glucose tolerance (NGT). RESULTS: Basal
      plasma levels of GIP and GLP-1 were not different between the groups. In response
      to the oral glucose ingestion, plasma levels of both GIP and GLP-1 increased in
      both groups. The plasma GIP increase after glucose ingestion was, however,
      reduced in women with IGT. Thus, the GIP response as determined as the area under
      the curve for the 60 min after oral glucose was 34.8 +/- 3.2 pmol/l per min in
      women with IGT versus 56.4 +/- 7.8 pmol/l per min in those with NGT (P = 0.021).
      In contrast, the GLP-1 response to oral glucose was not different between the
      groups. By definition, the glucose response to oral glucose was markedly
      increased in women with IGT, and the insulin response during the second hour
      after glucose ingestion was exaggerated. CONCLUSIONS: The GIP response to oral
      glucose is impaired in postmenopausal women with IGT, whereas the plasma GLP-1
      response is not affected.

PMID- 9272100
TI  - Serum free insulin-like growth factor-I in growth hormone-deficient adults before
      and after growth hormone replacement.
AB  - The objective of the present study was to compare fasting levels of free IGF-I in
      serum from patients with adult onset growth hormone deficiency (GHD) and from
      healthy volunteers, and to examine the effect of GH replacement therapy in GHD on
      serum free IGF-I. Free IGF-I was measured using separation of free IGF-I by
      ultrafiltration in serum samples from 42 healthy volunteers and 27 patients with
      GHD, in the latter before and after 1 year of treatment with GH (2 IU/m2) (n =
      13) or placebo (n = 14). Free IGF-I was significantly decreased in patients with
      GHD (700 +/- 100 ng/l (mean +/- S.E.M.), range 55-2618 ng/l) compared with
      controls (1010 +/- 70 ng/l, range 231-2431 ng/l; P = 0.0016). Total IGF-I was 85
      +/- 10 micrograms/l (GHD) and 160 +/- 10 micrograms/l (controls) (P < 0.0001).
      The ratio of free over total IGF-I was increased in GHD to 0.85 +/- 0.08%
      compared with 0.66 +/- 0.05% in controls (P = 0.04). In both GHD and controls,
      free IGF-I correlated significantly (P < 0.05) with total IGF-I (GHD r = 0.78;
      controls r = 0.42), IGFBP-1 (GHD r = -0.67; controls r = -0.46) and the molar
      ratio of total IGF-I over IGFBP-3 (GHD r = 0.58; controls r = 0.62). After 1 year
      of GH treatment, free IGF-I was increased to 2780 +/- 320 ng/l (P = 0.003) and
      total IGF-I was increased to 270 +/- 30 micrograms/l (P = 0.006) both of which
      values were greater than those in healthy volunteers. There were no changes in
      free or total IGF-I in the placebo-treated group. In conclusion, levels of free
      IGF-I are decreased in GHD, but measurements of free IGF-I in a single, fasting
      serum sample do not offer a better separation of patients with GHD from
      individuals with normal GH status than can be achieved by measurement of total
      IGF-I. One year of treatment with 2IU/m2 GH caused an increase of serum free IGF
      I to supraphysiological levels.

PMID- 9272101
TI  - Clinical trials of GH treatment in patients with Turner's syndrome in Japan--a
      consideration of final height. The Committee for the Treatment of Turner's
      Syndrome.
AB  - Clinical trials of human GH (hGH) therapy in Turner's syndrome were started in
      1986. Between 1986 and 1990. 362 patients were enrolled; 115 were treated for
      more than 6 years. The age at the start of treatment ranged from 5 to 18 years
      (mean 10 years). Fifty-one patients received hGH at a weekly dosage of 0.5 IU/kg
      and 64 received 1.0 IU/kg by daily s.c. injection. Both treatment groups showed a
      statistically significant growth increase during the initial 4 years of
      treatment. The rate of increase in height was significantly greater for the
      initial 2 years with the high dose than with the low dose. The increases in
      height over 6 years of treatment (expressed by S.D. score for chronological age)
      were 1.48 +/- 0.8 with 0.5 IU/kg per week and 1.80 +/- 1.0 with 1.0 IU/kg per
      week. To date, 260 patients have stopped GH therapy. In 32% of them, the height
      attained was above the -2 S.D. value for normal girls. In 27%, the growth rate
      was not sufficient when they stopped treatment. The mean final height (growth
      rate < or = 1.0 cm/year) of patients treated for more than 6 years was 142.2 +/-
      6.5 cm (n = 15) with 0.5 IU/kg per week, and 144.3 +/- 3.9 cm (n = 15) with 1.0
      IU/kg per week. The adult height was improved by GH treatment, although final
      height did not differ statistically between the two dose regimens. No remarkable
      adverse events occurred during the treatment. These results indicate that hGH
      treatment improves the final height in patients with Turner's syndrome.

PMID- 9272102
TI  - The effects of two doses of replacement growth hormone on the biochemical, body
      composition and psychological profiles of growth hormone-deficient adults.
AB  - This study examined the effects of growth hormone (GH) replacement on the insulin
      like growth factor-I (IGF-I), body composition and psychological profiles of GH
      deficient adults. We assessed whether two doses of GH produced different effects
      on these variables and whether patients who, at the end of the study chose to
      remain on long-term GH replacement responded differently to those who chose to
      abandon therapy. Forty-two adults (aged 42.9 +/- 1.9 years (mean +/- S.E.M.))
      with documented GH deficiency entered two studies (24 in study 1, 18 in study 2).
      Biochemical, body composition and psychological profiles were assessed at
      baseline, and after 6 months and 1 year. Psychological assessments were performed
      using well-established, independent, validated 'Quality of Life' questionnaires
      (Nottingham Health Profile (NHP) and the Psychological General Well-Being
      Schedule (PGWB)). The study protocols differed only in the doses of growth
      hormone (0.024 mg/kg per day and 0.012 mg/kg per day respectively). Comparison
      between studies and between patients eventually continuing and abandoning GH
      therapy was performed. GH replacement was associated with significant changes in
      IGF-I levels (P < 0.001), body composition (P < 0.01) and self-perceived well
      being (NHP, P < 0.01; PGWB, P < 0.01). The higher dose of GH produced a greater
      IGF-I response than the lower dosage (44.6 +/- 7.3 vs 26.2 +/- 3.6 nmol/l, P <
      0.05), but no better psychological response (NHP, P = 0.22; PGWB, P = 0.23).
      Those deciding to continue replacement therapy did not respond differently to
      those choosing to abandon therapy with respect to IGF-I (P = 0.72), body
      composition (P = 0.38) and psychological assessment (NHP, P = 0.29; PGWB, P =
      0.24). GH replacement in GH-deficient adults was associated with significant
      improvements in self-perceived well-being as well as changes in body composition
      and other variables. This improvement was similar at two different doses of
      replacement GH. Those patients electing to continue on long-term replacement did
      not achieve a demonstrably different psychological, body composition or
      biochemical benefit to those patients deciding to discontinue replacement.

PMID- 9272103
TI  - Impaired vasopressin suppression and enhanced atrial natriuretic hormone release
      following an acute water load in primary aldosteronism.
AB  - The release of arginine vasopressin (AVP) and atrial natriuretic hormone (ANH)
      and their involvement in renal water and electrolyte metabolism in primary
      aldosteronism in humans were studied. An oral acute water load (20 ml/kg body
      weight) was given to each of 12 patients before and after surgical removal of
      their aldosterone-producing adenoma(s). Plasma AVP and ANH were measured
      simultaneously, and renal water and electrolyte metabolism and tubular functions
      were determined. The same water load was given to seven normal subjects and the
      same parameters were determined. In the presence of mineralocorticoid excess
      before the operation, plasma AVP was relatively low compared with plasma
      osmolality (Posm), but was not suppressed in response to decreases in Posm after
      the water load. Baseline plasma ANH was high and increased further after the
      water load; urinary dilution and diuresis both remained normal. After the
      operation, baseline plasma AVP was normal and decreased in response to the
      decrease in Posm after the water load, with normal urinary dilution and diuresis.
      Baseline plasma ANH was normal, and did not increase after the water load. The
      ratio of urinary K and Na clearances and distal tubular reabsorption of Na
      increased before the operation. These results suggest that there are
      perturbations of AVP and ANH release in primary aldosteronism, despite the normal
      urinary dilution after a water load.

PMID- 9272104
TI  - Resistance to vasopressin action on the kidney in patients with Cushing's
      disease.
AB  - OBJECTIVE: To assess the plasma levels and action of arginine vasopressin (AVP)
      in patients with Cushing's disease. There are many reports that patients with
      Addison's disease have increased AVP levels associated with hyponatraemia and
      hypoosmolality, but none on the dynamics of secretion of this neurohormone during
      osmolality-based stimulation in patients with chronic hypercortisolism. DESIGN
      AND SUBJECTS: The plasma AVP concentration and the urinary and plasma osmolality
      after a 7.5-h water deprivation test (WDT) were evaluated in 13 patients with
      Cushing's disease and 15 normal (control) individuals. In patients with Cushing's
      disease we also assessed the urinary osmolality in response to 10 micrograms i.v.
      desmopressin (DDAVP) administered at the end of the WDT. RESULTS: At the end of
      the WDT, urinary osmolality was significantly lower in patients with Cushing's
      disease (511.5 +/- 148.5 mOsm/l) than in the normal subjects (981.1 +/- 107.1
      mOsm/l, P < 0.001), whereas plasma osmolality did not differ between the two
      groups. Consequently, the urine/plasma osmolality ratio (Uosm/Posm) was lower in
      patients with Cushing's disease than in normal individuals (1.8 +/- 0.5 compared
      with 3.4 +/- 0.4, P < 0.001). The AVP concentration also was greater (7.3 +/- 3.1
      pmol/l) in those with Cushing's disease than in the controls (3.9 +/- 2.3 pmol/l,
      P < 0.005). After administration of DDAVP to the hypercortisolaemic patients, the
      urinary osmolality attained (718.0 +/- 200.0 mOsm/l) was still lower than that in
      the normal group at the end of WDT (P < 0.005). CONCLUSIONS: Patients with
      Cushing's disease presented higher AVP levels and smaller Uosm/Posm ratios than
      normal subjects. After DDAVP, the patients with Cushing's disease were unable to
      concentrate the urine adequately. These data suggest that the kidney shows
      resistance to the action of both endogenous and exogenous AVP in patients with
      Cushing's disease.

PMID- 9272106
TI  - One microgram is the lowest ACTH dose to cause a maximal cortisol response. There
      is no diurnal variation of cortisol response to submaximal ACTH stimulation.
AB  - There are many suggestions in the literature that the adrenal gland is more
      sensitive to ACTH in the evening than in the morning. However, all these studies
      in humans were conducted when the basal cortisol level was not suppressed, and
      were based on the observation that, after stimulation, the increases in cortisol
      differed, though the peak values were the same. To examine this, we established
      the lowest ACTH dose that caused a maximal cortisol stimulation even when the
      basal cortisol was suppressed, and used a smaller dose of ACTH for morning and
      evening stimulation. The lowest ACTH dose to achieve maximal stimulation was
      found to be 1.0 microgram, with which dose cortisol concentration increased to
      607.2 +/- 182 nmol/l, compared with 612.7 +/- 140.8 nmol/l with the 250
      micrograms test (P > 0.3). The use of smaller doses of ACTH (0.8 and 0.6
      microgram) achieved significantly lower cortisol responses (312 +/- 179.4 and 323
      +/- 157.3 nmol/l respectively; both P < 0.01 compared with the 1 microgram test).
      When a submaximal ACTH dose (0.6 microgram) was used to stimulate the adrenal at
      0800 and 1600 h, after pretreatment with dexamethasone, no difference in response
      was noted at either 15 min (372.6 +/- 116 compared with 394.7 +/- 129.7 nmol/l)
      or 30 min (397.4 +/- 176.6 compared with 403 +/- 226.3 nmol/l; P > 0.3 for both
      times). These results show that 1.0 microgram ACTH, used latterly as a low-dose
      test, is very potent in stimulating the adrenal, even when baseline cortisol is
      suppressed; smaller doses cause reduction of this potency. Our data show that
      there is probably no diurnal variation in the response of the adrenal to ACTH, if
      one eliminates the influence of the basal cortisol level and uses physiologic
      rather than superphysiologic stimuli.

PMID- 9272107
TI  - ACTH-producing carcinoma of the pituitary with haematogenic metastases.
AB  - The case report is presented of a 47-year-old white woman with Cushing's disease
      treated by bilateral adrenalectomy in June 1981. A first computed tomography (CT)
      scan in September 1984 showed a voluminous pituitary adenoma with invasion of the
      sphenoid sinus and left parasellar extension. The tumour increased progressively
      in size, a suprasellar extension developed and the optic chiasm was eventually
      affected. In March 1988 and June 1989 the patient underwent two surgeries for the
      pituitary tumour, the second followed by radiotherapy. During this period, the
      ACTH values varied between 100 pmol/l and 403 pmol/l (normal: < 13 pmol/l). After
      radiotherapy, a progressive shrinking of the tumour was observed and the ACTH
      concentrations decreased to a lowest value of 27.5 pmol/l. The patient was
      clinically well until September 1993 when, suddenly, the plasma ACTH
      concentration increased to very high levels (greater than 965 pmol/l). There was
      no evidence of tumour growth on the sellar CT scan. In January 1995, an ACTH
      producing pituitary carcinoma was diagnosed, based on the presence of bone
      metastases. The patient died in May 1995.

PMID- 9272105
TI  - Change in C-terminal cross-linking domain of type I collagen in urine, a new
      marker of bone resorption, during and after gonadotropin-releasing hormone
      agonist administration.
AB  - OBJECTIVE: The major side effect of GnRH agonist (GnRHa) therapy is the reduction
      of bone mass. To analyze bone resorption by GnRHa, we measured the urinary
      excretion of C-terminal telopeptides of type I collagen (CTX), a new marker of
      bone resorption. METHODS: We used a new ELISA for CTX (CrossLaps) in a sample of
      18 premenopausal women with leiomyoma who were treated with daily administration
      of 400 micrograms nafarelin or 900 micrograms buserelin for 16 weeks. RESULTS:
      Urinary CTX excretion increased significantly during GnRHa treatment and then
      decreased at 12 and 24 weeks after the cessation of GnRHa therapy. Whereas the
      excretory profile of CTX during GnRHa therapy was almost similar to that of
      pyridinoline (Pyr) or deoxypyridinoline (D-Pyr), both biochemical markers of bone
      resorption, the magnitude of the change in CTX was significantly greater than
      that in Pyr or D-Pyr. CONCLUSIONS: These results indicate that CTX could be a
      more sensitive marker for bone resorption than the currently used biochemical
      markers, and that CrossLaps ELISA is useful for therapeutic monitoring during and
      after GnRHa treatment.

PMID- 9272108
TI  - Molecular structure of the human gonadotropin-releasing hormone receptor gene.
AB  - GnRH receptors belong to the family of G protein-coupled receptor proteins and
      have been localized to the anterior pituitary, brain and reproductive organs as
      well as many steroid-dependent tumor tissues. Recently, cDNAs for the GnRH
      receptors of several species including the human have been cloned. To determine
      the structure of the gene encoding the human GnRH receptor, we isolated the
      receptor gene clones from the human genomic libraries. Comparison of the genomic
      and cDNA sequences revealed that the human GnRH receptor gene is composed of
      three exons and two introns and spans over 20 kb in size. Exon 1 encodes the 5'
      untranslated sequence and nucleotide +1 to +522 in the open reading frame, exon 2
      encodes nucleotide +523 to +742 and exon 3 encodes nucleotide +743 to +987 in the
      open reading frame as well as the 3' untranslated sequence. Southern blot
      analysis of genomic DNA and localization of the GnRH receptor gene to a single
      site on human chromosome 4 (4q13) indicate the presence of a single copy of the
      gene in the human genome. Several regulatory sequences for various hormones and
      other regulatory factors were identified, including PEA-3, AP-1, AP-2, and Pit-1
      sites. In addition, glucocorticoid/progesterone response element thyroid hormone
      response element, and cAMP response element sequences were identified. Reverse
      transcriptase-primer extension and 5' RACE analysis of the human pituitary RNA
      demonstrated the presence of multiple transcriptional start sites upstream of the
      translational start site. Analysis of the 5' flanking region of the gene also
      revealed the presence of multiple TATA and CAAT sequences. The finding of
      multiple transcriptional start sites raises the possibility of tissue-specific
      regulation and the existence of variable size transcripts. Chimeras containing
      1.26 kb (-534 to 728) of the 5' flanking region of the receptor gene and the
      luciferase (Luc) gene expressed a significant luciferase activity when
      transfected into a human endometrial tumor cell line (HEC-1A) and a breast tumor
      cell line (MCF-7) but not in a mouse pituitary gonadotrope cell line (alpha T3
      1), suggesting the existence of multiple promoter elements in the gene. These
      findings indicate a multiplicity of regulation of expression of the GnRH receptor
      and provide the substrate for detailed investigation in the reproductive system.

PMID- 9272109
TI  - Effect of the somatostatin analog, octreotide, and of other hormones on the
      release of the acid-labile subunit of the 150 kDa complex by rat hepatocyte in
      primary culture.
AB  - OBJECTIVE: In normal subjects, the major form of circulating IGF is the GH
      dependent 150 kDa complex. The liver appears to be the main source of the three
      components of the 150 kDa complex and, in particular, hepatocytes synthesize the
      insulin-like growth factor (IGF) peptide and the acid-labile subunit (ALS),
      whereas Kupffer and sinusoidal endothelial cells produce IGF-binding protein-3
      (IGFBG-3). We have studied the effects of the somatostatin analog octreotide, IGF
      II des(1-3)IGF-I, transforming growth factor (TGF)-beta 1 and tri-iodothyronine
      (T3) on ALS secretion into the medium conditioned by rat hepatocytes in primary
      culture. METHODS: The regulation of ALS release was evaluated in the conditioned
      medium of adult rat hepatocytes exposed to increasing concentrations of test
      substances or to vehicle alone (control), after gel filtration in basic
      conditions, by immunoblot using an antiserum generated against the N-terminal 34
      amino acids of human ALS. RESULTS: The results demonstrate that: 1) octreotide in
      vitro produces a dose-dependent inhibition of both basal and GH-stimulated ALS
      secretion into the hepatocyte conditioned medium; 2) the release of ALS by adult
      rat hepatocytes is not affected by the presence during the incubation of des(1
      3)IGF-I or IGF-II; 3) an inhibitory effect, although only with very high doses,
      can be observed after treatment with TGF-beta 1; and 4) a small but significant
      increase of ALS released into the medium can be seen when hepatocytes are treated
      with T3. CONCLUSIONS: Evaluation of the effect of substances known to affect the
      production of IGF peptides, the IGFBPs, or both, on adult rat hepatocytes in
      primary culture revealed no powerful stimulator, but instead a potent inhibitor
      of ALS release/synthesis. Our data suggest that the effect of somatostatin on the
      150 kDa complex is mediated not only by the reduction in GH concentration, but
      also by a direct inhibition of ALS release or synthesis.

PMID- 9272110
TI  - Relationship between the release of prolactin and endothelin-1 in human
      decidualized endometrial cells.
AB  - The study was undertaken to investigate the interaction between the release of
      endothelin-1 (ET-1) and prolactin (PRL) from human decidualized endometrial
      cells, and the effects of transforming growth factor (TGF)-beta 1 on the release
      of ET-1 and PRL from human decidual cells in the early stage of pregnancy.
      Stromal cells derived from human endometrial tissues were cultured on a type-1
      collagen membrane in serum-free medium with or without 100 nmol/l oestradiol and
      1 mumol/l medroxyprogesterone acetate (MPA) for 12 days. In addition, decidual
      cells of early pregnancy were cultured with or without TGF-beta 1 for 48 h. PRL
      and ET-1 levels in the media were measured by a specific enzyme immunoassay and
      RIA respectively. In decidualized endometrial cells induced by ovarian steroid
      hormones in vitro, PRL release increased and ET-1 release decreased in a time
      dependent manner. Ovarian steroid hormones significantly attenuated ET-1 release.
      In the decidual cells of early pregnancy, TGF-beta 1 significantly attenuated the
      PRL release, whereas this growth factor dose-dependently increased ET-1 release.
      There was a significant negative correlation between the release of PRL and that
      of ET-1. These results demonstrate that the regulation of PRL release is quite
      different from that of ET-1 release in the human decidualized endometrial cells,
      and suggest that TGF-beta 1 has significant effects on PRL and ET-1 release in
      the human decidua of early pregnancy.

PMID- 9272111
TI  - 17 beta-Oestradiol inhibits stimulated endothelin release in human vascular
      endothelial cells.
AB  - Oestrogen is believed to possess cardiovascular protective properties. Endothelin
      1 (ET-1) is a potent vasoconstrictor and mitogen for vascular smooth muscle
      cells. We have investigated release of ET-1 from human endothelial cells in
      response to 17 beta-oestradiol. Serum was found to stimulate significantly ET-1
      release during the first 4 h of culture. 17 beta-Oestradiol significantly reduced
      ET-1 immunoreactivity in the media of treated cells by up to 49% of control
      values after 4 h. This effect was found to be inversely related to the dose of 17
      beta-oestradiol. Significant dose-dependent increases in nitric oxide synthase
      expression were observed in response to oestrogen after 24 h but not after 4 h.
      Serum-free experiments demonstrated that low doses of oestrogen were able to
      inhibit thrombin-induced ET-1 release whilst supraphysiological levels did not.
      These results provide a further perspective on the ability of oestrogens to
      maintain vascular health.

PMID- 9272112
TI  - Combined intravenous and oral mesna in outpatients treated with ifosfamide.
AB  - PURPOSE: To prevent hemorrhagic cystitis, mesna is typically injected
      intravenously (i.v.) at the time of an ifosfamide dose and 4 and 8 h later. To
      simplify outpatient ifosfamide therapy, we gave the second and third mesna doses
      orally. METHODS: The mesna doses (400 or 600 mg/m2) were 40% (w/w) of each
      ifosfamide dose (1.0 or 1.5 g/m2), which was given daily for 5 days. We evaluated
      urinary mesna excretion and plasma concentrations in ten patients from the
      beginning of mesna infusion until the time of the second oral dose. The first
      oral dose was administered at hour 2 in the last six patients to allow time for
      absorption of mesna. RESULTS: The rate and amount of mesna excretion was less
      variable over time and among patients after oral than after i.v. administration.
      No macrohematuria was observed in these ten patients nor in an additional 50
      patients given oral mesna at hours 2 and 8 during at least two cycles of
      ifosfamide therapy. CONCLUSION: These pharmacokinetic and clinical efficacy data
      support the use of a combined regimen of i.v. and oral mesna to simplify
      outpatient ifosfamide administration.

PMID- 9272113
TI  - Apoptosis induced in advanced CD8F1-murine mammary tumors by the combination of
      PALA, MMPR and 6AN precedes tumor regression and is preceded by ATP depletion.
AB  - The drug combination N-(phosphonacetyl)-L-aspartic acid (PALA),
      methylmercaptopurine riboside (MMPR) and 6-aminonicotinamide (6AN), referred to
      as PMA, induces regressions of advanced CD8F1 murine mammary carcinomas in vivo.
      We demonstrated that CD8F1 tumor regressions were preceded by the appearance of
      apoptotic bodies, as observed by microscopic examination of morphology and TUNEL
      endlabeling, and fragmentation of DNA into nucleosomal "ladder" patterns. These
      indications of apoptosis were present as early as 6 h after simultaneous
      administration of MMPR and 6AN and further increased by over fivefold during the
      next 3 to 6 h, then remained at 7 to 12.8% (0.6 to 2.4% in saline-treated
      controls) of the cell population for at least 24 h after MMPR + 6AN
      administration. The 5'-phosphate derivative of MMRP, MMPR-5P, which inhibits de
      novo purine biosynthesis, was present at a "steady-state" level, and significant
      (40%) depletion of ATP had occurred by 3 h and both of these events preceded the
      onset of apoptosis. In addition, MMPR-5P was retained in CD8F1 tumors at a high
      level over a prolonged period (> 96 h) even as tumors were undergoing regression.
      The prolonged presence of MMPR-5P was important for optimal chemotherapeutic
      effect, since treatment with iodotubercidin (IodoT), an inhibitor of
      MMPR/adenosine kinase, 6 h after MMPR+6AN administration prevented the prolonged
      accumulation of MMPR-5P and reversed the regression of CD8F1 tumors. In addition,
      compared to the PMA-treated group, there was a significant restoration of ATP
      levels after treatment with IodoT. In individual PMA-treated CD8F1 tumors the
      degree of ATP depletion was found to correlate with the degree of tumor shrinkage
      at 24 h, after tumors had sufficient time to respond to treatment. These results
      define the time-course of drug-induced apoptosis in CD8F1 tumors, show that ATP
      depletion occurs prior to apoptosis and demonstrate that prolonged retention of
      MMPR-5P is associated with optimal chemotherapy. Collectively, these results
      suggest that the depletion of ATP by PMA treatment may be a component of the
      biochemical apoptotic cascade in the CD8F1 tumor.

PMID- 9272114
TI  - Potentiation of cisplatin and carboplatin cytotoxicity by amphotericin B in
      different human ovarian carcinoma and malignant peritoneal mesothelioma cells.
AB  - An in vitro study of the combined cytotoxicity of either cisplatin (CDDP) or
      carboplatin and amphotericin B (AmB) was undertaken on a set of different ovarian
      carcinoma (IGROVI, IGROVI-C10, OAW42) and peritoneal malignant mesothelioma (CFB
      CARP1) cell lines and ascitic cells freshly obtained from ovarian cancer patients
      so as to investigate the possibility of overcoming their resistance to platinum
      compounds. Growth-inhibition curves obtained 6 days after a 2-h period of
      exposure to the drugs showed that AmB at 5-10 mg/l allowed a 5- to 10-fold
      decrease in the 50% growth-inhibitory concentrations (IC50) of CDDP and
      carboplatin on either sensitive or resistant cells. Intracellular platinum assays
      with IGROVI cells showed that AmB acted by increasing dramatically the platinum
      uptake at a proportion that accounted for the increase in cytotoxicity. In the
      subline IGROVI-C10, a 10-fold resistant subline of IGROVI, AmB at 10 mg/l allowed
      recovery to the level of sensitivity seen in the parental cell line in the
      absence of AmB but not to the level observed in the presence of AmB. Acquisition
      of resistance mechanisms that are independent of the regulation of platinum
      uptake might be involved in this cell line. Thus, AmB might act by increasing the
      intracellular concentration of platinum without modifying the resistance
      mechanism involved downstream. However, in our models an increase in the
      intracellular level of platinum was always sufficient for the recovery of
      chemosensitivity in vitro. We also show that the phosphodiesterase inhibiting
      methylxanthines act synergistically with AmB. The latter drugs are weakly toxic
      and could also attenuate the nephrotoxicity of AmB.

PMID- 9272115
TI  - Urinary stability of carboxycyclophosphamide and carboxyifosfamide, two major
      metabolites of the anticancer drugs cyclophosphamide and ifosfamide.
AB  - Phosphorus-31 nuclear magnetic resonance spectroscopy was used to evaluate the
      stability of carboxycyclophosphamide (CXCP) and carboxyifosfamide (CXIF) in human
      urine at pH 7.0 and 5.5 at 25 degrees, 8 degrees, -20 degrees, and -80 degrees C.
      At 25 degrees C and pH 7.0, CXCP and CXIF are relatively stable (approximately
      10% degradation in 24 h). In contrast, they are much less stable at pH 5.5
      (approximately 80% degradation of CXIF and approximately 50% degradation of CXCP
      in 24 h). The rate of degradation of CXCP and CXIF was a function of the storage
      temperature of the urine samples but, even at -80 degrees C, was not negligible:
      approximately 30% degradation for CXCP irrespective of pH and approximately 40%
      and 50% degradation for CXIF at pH 7.0 and 5.5, respectively, after storage for 6
      months. CXCP was more stable than CXIF at either pH (7.0 or 5.5) and at all
      storage temperatures (8 degrees, -20 degrees, or -80 degrees C) of the urine
      samples. CXCP and CXIF were more stable at pH 7.0 than at pH 5.5, although this
      difference fell with decreasing temperatures to be almost negligible at -80
      degrees C. To ensure a true estimate of CXCP and CXIF levels, urine samples must
      be frozen and stored at -80 degrees C within a few hours of micturition. CXCP and
      CXIF assays should also be carried out within 2 months and 1 month of storage,
      respectively.

PMID- 9272116
TI  - Comparison of the protective effects against chronic doxorubicin cardiotoxicity
      and the rates of iron (III) displacement reactions of ICRF-187 and other
      bisdiketopiperazines.
AB  - Histologic and biochemical studies were carried out to compare the protective
      activity of various bisdiketopiperazines against the cardiac and renal toxicity
      induced by doxorubicin in spontaneously hypertensive rats (SHR), a well
      established animal model of this disorder, with: (1) the rates of hydrolysis of
      these agents to form the iron-chelating derivatives (which are considered to
      cause a decrease in the formation of reactive oxygen intermediates) and (2) the
      ability of these derivatives to bind iron. SHR were given 12 weekly injections of
      doxorubicin, 1 mg/kg i.v. either alone or 30 min after the administration of ICRF
      154, ICRF-187, ICRF-192, ICRF-197, ICRF-198, ICRF-239 and ADR-559.
      Semiquantitative grading of the severity of the resulting cardiac and renal
      lesions showed that ICRF-187, ICRF-154 and ADR-559 were the most protective,
      whereas ICRF-197 and ICRF-239 provided intermediate degrees of protection, and
      ICRF-192 and ICRF-198 were not protective. Quantitative measurements in vitro
      revealed only relatively small differences in the rates of opening of the two
      diketopiperazine rings of the various agents to form the corresponding iron
      chelating diacid diamide derivatives, and in the ability of these various
      derivatives to remove iron from the iron-doxorubicin complex. Such differences
      showed no relationship with cardioprotective activity. Some bisdiketopiperazines
      (including ICRF-154 and ICRF-187) with cardioprotective activity also are
      inhibitors of DNA topoisomerase II; however, the significance of this
      relationship remains uncertain, since ADR-925, the open-ring derivative of ICRF
      187, does not inhibit DNA topoisomerase II.

PMID- 9272117
TI  - Characterization of the mechanisms of busulfan resistance in a human glioblastoma
      multiforme xenograft.
AB  - Busulfan is an alkylating agent commonly used in the treatment of chronic
      myelogenous leukemia and in combination with cyclophosphamide in preparation for
      allogeneic bone marrow transplantation. Serial treatment of a childhood high
      grade glioma xenograft (D-456 MG) with busulfan resulted in a busulfan-resistant
      xenograft, D-456 MG(BR). Cross-resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea
      was seen but not resistance to cyclophosphamide or CPT-11. Cytoplasmic levels of
      glutathione in D-456 MG(BR) were approximately one-half those found in D-456 MG.
      This depletion could not be explained by levels of glutathione-S-transferase, or
      by amplification, rearrangement, or increased levels of transcript of gamma
      glutamylcysteine synthetase. Furthermore, depletion of glutathione in D-456 MG
      did not alter busulfan activity. Quantitation of busulfan levels in D-456 MG and
      D-456 MG(BR) xenografts following treatment of mice at the dose lethal to 10% of
      the animals demonstrated that significantly lower levels of drug were achieved in
      D-456 MG(BR). These studies suggest that alterations in drug transport or
      metabolism of busulfan may play a role in the resistance of D-456 MG(BR) to this
      alkylator.

PMID- 9272118
TI  - Phase II trial of chloroquinoxaline sulfonamide (CQS) in patients with stage III
      and IV non-small-cell lung cancer.
AB  - PURPOSE: Chloroquinoxaline sulfonamide (CQS) was one of the first agents
      identified by the human tumor colony-forming assay (HTCFA) as possessing
      antitumor activity in non-small-cell lung cancer (NSCLC). Prior phase I studies
      had suggested that plasma concentrations equivalent to those showing efficacy in
      the HTCFA could be reliably attained in humans. This phase II study assessed the
      antitumor activity of CQS while using an adaptive control pharmacokinetic
      modelling system to attain targeted plasma levels of this novel compound.
      METHODS: A group of 20 patients with stage III or IV NSCLC received CQS as a 1-h
      weekly infusion at an initial dose of 2 g/m2. In all patients, 24-h plasma
      concentrations of CQS were measured. Patients with levels < 100 micrograms/ml had
      dose increases determined by their 24-h levels and pharmacokinetic parameters
      obtained from two prior phase I trials of this agent. These individuals had 24-h
      CQS levels repeated after their second weeks' treatment and doses were readjusted
      if the target concentration was not reached. Antitumor response assessment was
      made every 6 weeks. RESULTS: Of the 20 patients, 18 attained the target plasma
      concentration, and 16 of these achieved this initially or with just one dose
      adjustment. No major objective antitumor responses were observed (major response
      rate 0%, 95% CI 0-17%). CQS was well tolerated with hypoglycemia being the most
      clinically significant toxicity. CONCLUSIONS: When given on this schedule CQS is
      inactive in NSCLC despite the fact that the target concentration was achieved in
      90% of patients. The ability of the HTCFA to identify active agents remains
      unproved.

PMID- 9272119
TI  - Pharmacokinetics of doxorubicin and epirubicin in mice during chlorpromazine
      induced hypothermia.
AB  - Blood concentrations of doxo- and epirubicin were studied in mice after i.v. or
      i.p. administration under normal and hypothermic conditions. The animals either
      were pretreated i.p. with chlorpromazine at 15 mg/kg and allowed to cool to a
      rectal temperature of 28 degrees C or were given saline i.p. with their rectal
      temperature remaining at 37 degrees C. The anthracyclines were 14-14C-labeled and
      were given at a dose of 0.85 mg/kg. Blood samples were taken at 5, 15, and 25 min
      and 2, 6, 24, and 48 hours after injection and were analyzed by liquid
      scintillation counting. The blood concentration related to time was similar for
      the two anthracyclines. The peak concentration was highest for i.v.
      administration and was higher for the hypothermic groups. The peak concentration
      and the area under the curve were highest under hypothermic conditions. The
      terminal half-life was longer after i.p. administration. The ratio calculated for
      the blood concentration under hypothermic/normothermic conditions over time was
      substantially increased after i.p. administration, the increase being most
      pronounced for epirubicin. The pharmacokinetic characteristics found might be
      related to the anthracycline toxicity encountered in tumor-inoculated mice
      treated at different body temperatures.

PMID- 9272120
TI  - A novel quinoline derivative, MS-209, overcomes drug resistance of human lung
      cancer cells expressing the multidrug resistance-associated protein (MRP) gene.
AB  - PURPOSE AND METHODS: MS-209 is a newly synthesized quinoline compound used orally
      to overcome human P-glycoprotein (Pgp)-mediated multidrug resistance (MDR). The
      multidrug resistance-associated protein (MRP) gene is thought to play an
      important role in MDR in lung cancer. To investigate whether MS-209 could also
      overcome MRP-mediated MDR, we examined the effect of the compound using a
      cytotoxicity assay on MDR1 gene-negative drug-selected MDR and wildtype lung
      cancer cells with various levels of MRP gene expression. The effects of MS-209
      were compared with those of verapamil (VER) and cyclosporin A (CsA). The level of
      MRP gene expression in the cells was evaluated semiquantitatively by RT-PCR. For
      vincristine (VCR), intracellular accumulation of [3H]-VCR was measured with or
      without MS-209. RESULTS: In MDR UMCC-1/VP small-cell lung carcinoma cell line, 5
      microM of MS-209 and VER enhanced the cytotoxicity of etoposide, doxorubicin
      (DOX) and VCR more than twofold, and completely reversed the resistance to VCR.
      The mean reversing effects of MS-209 on DOX and VCR were significantly stronger
      than those of VER and CsA. In wildtype non-small-cell lung carcinoma cells, the
      effects of MS-209 were almost equal to those of VER and CsA. The effect of these
      three agents correlated with the level of MRP gene expression. The MS-209-induced
      increase in intracellular accumulation of VCR was proportional to the level of
      MRP gene expression in these cells. CONCLUSION: Our results indicate that MS-209
      is a potentially useful drug that can overcome MRP-mediated intrinsic and
      acquired MDR in human lung cancer.

PMID- 9272121
TI  - Differential cytotoxicity of clinically important camptothecin derivatives in P
      glycoprotein-overexpressing cell lines.
AB  - Camptothecin and its derivatives are specific inhibitors of eukaryotic
      topoisomerase I (top1) and are active in cancer patients against a variety of
      refractory solid tumors and leukemia. PURPOSE: The present study further
      investigated the relationship between multidrug resistance (MDR) mediated by P
      glycoproteinMDR and potential resistance to camptothecin derivatives using two
      experimental systems: (1) MDR KB-V1 cells selected for vinblastine resistance,
      and (2) NIH3T3 cells transfected with a plasmid expressing wildtype P
      glycoproteinMDR multidrug transporter (NIH-MDR-G185). RESULTS: We found that both
      KBV-1 and NIH-MDR-G185 cells were resistant to topotecan, and that topotecan
      induced cleavable complexes were reduced in KB-V1 cells, consistent with a role
      of P-glycoproteinMDR in cellular resistance to topotecan. By contrast, no
      significant resistance to camptothecin, 9-aminocamptothecin, 10, 11
      methylenedioxycamptothecin, or SN-38 (the active metabolite of CPT-11) was
      observed in NIH-MDR-G185 cells, while KB-V1 cells were cross-resistant to these
      compounds but produced cleavable complexes similar to those produced by parental
      KB-3-1 cells. CONCLUSIONS: These results suggest that topotecan is the only
      camptothecin tested with significant susceptibility to MDR in cell culture, and
      that multidrug resistant cells such as KBV1 probably exhibit additional
      resistance mechanisms to camptothecins besides P-glycoproteinMDR overexpression.

PMID- 9272122
TI  - Zeniplatin in advanced malignant melanoma and renal cancer: phase II studies with
      unexpected nephrotoxicity.
AB  - The antitumor activity of zeniplatin, a third-generation, water-soluble platinum
      compound that has shown broad preclinical antitumor activity and no significant
      nephrotoxicity in phase I trials, was tested in patients with advanced malignant
      melanoma and advanced renal cancer. Patients who had not previously been treated,
      except with local limb perfusion and immunotherapy, were given zeniplatin as
      bolus injections at 125 mg/m2 every 3 weeks. The main hematological toxicity was
      leukopenia (7/30 patients, WHO grade > or = 3) and the main nonhematological
      toxicity was nausea and vomiting (21/30 patients, WHO grade > or = 2). Serious
      nephrotoxicity was observed early in the renal cancer study and, later, also in
      the melanoma study. Hyperhydration did not prevent the nephrotoxicity, and the
      studies were stopped after 6 renal cancer patients and 24 malignant melanoma
      patients had been included. Zeniplatin gave objective responses in 3 of the 21
      evaluable malignant melanoma patients [2 complete responses (CRs) in patients
      with lymph-node metastases lasted 5 and 14 months, respectively; 1 partial
      response (PR) in a patient with lymph-node and liver metastases lasted 6 months].
      In the renal cancer study, only four patients were evaluable for response and
      none responded. The results show that zeniplatin has some activity (14%) in
      patients with advanced malignant melanoma, but no conclusion can be drawn
      regarding the activity of zeniplatin in renal cancer as the number of patients
      was too low. The main toxicities were leukopenia and nausea and vomiting.
      Unexpected and serious nephrotoxicity was observed, and for this reason the
      studies were terminated before the planned number of patients had been included.
      A possible explanation for the nephrotoxicity may be drug interactions, but no
      firm conclusion can yet be drawn.

PMID- 9272123
TI  - Digitonin enhances the efficacy of carboplatin in liver tumour after intra
      arterial administration.
AB  - Platinum-containing drugs enter the cell slowly and have a poor tissue
      penetration. Increasing the permeability of the cell membrane might increase the
      intracellular drug concentration. Digitonin, a detergent that increases cell
      permeability by binding to cholesterol molecules in the cell membrane, can
      increase cisplatin accumulation and reduce tumour growth in vitro. The aim of
      this study was to determine whether digitonin could increase the efficacy of
      carboplatin (CBDCA) in vivo. In LH rats, a hepatoma was implanted in the liver.
      At 7 days after implantation, digitonin (or saline in the control group) was
      infused via the hepatic artery and, 10 min later, CBDCA was injected. Biopsies
      from the tumour and liver parenchyma were obtained after 1 h. The concentration
      of platinum measured in the liver tumours was higher in the digitonin group than
      in the control groups. In the liver parenchyma the concentrations were of the
      same magnitude. Measured with the 133Xe-clearance technique, digitonin did not
      alter the tumour blood flow. Digitonin enhanced the tumour-growth-retarding
      effect of CBDCA given intra-arterially at 5 mg/kg but not at 25 mg/kg. No
      increase in toxicity was observed for digitonin given together with CBDCA at 5
      mg/kg. Systemic administration of CBDCA was not influenced by digitonin. These
      findings demonstrate that pretreatment with digitonin increases the tumour uptake
      of CBDCA and potentiates the cytotoxic effect of CBDCA.

PMID- 9272124
TI  - Salivary drug monitoring of irinotecan and its active metabolite in cancer
      patients.
AB  - To assess the clinical usefulness of salivary monitoring of irinotecan (CPT-11)
      and its active metabolite (SN-38), we examined the clinical pharmacological
      profile of both drugs in 9 patients with thoracic malignancies who received 60
      mg/m2 CPT-11 (21 courses). Plasma and unstimulated whole saliva were collected
      over a 24-h period, and concentrations of CPT-11 and SN-38 were measured by high
      performance liquid chromatography. Both CPT-11 and SN-38 were detectable in
      saliva, and the concentration-time curves in plasma and saliva showed a very
      similar pattern. A good correlation was observed between the saliva concentration
      (C3) and the plasma concentration (Cp) for both CPT-11 and SN-38 (r = 0.732, P <
      0.0001 and r = 0.611, P < 0.0001, respectively). The area under the concentration
      time curve calculated for saliva (AUCs) correlated with that generated for plasma
      (AUCp) for both CPT-11 and SN-38 (r = 0.531, P = 0.012 and r = 0.611, P = 0.0025,
      respectively). These results suggest that it may be feasible to use saliva
      instead of plasma for pharmacokinetics/pharmacodynamics studies of CPT-11.

PMID- 9272125
TI  - An N-myristoylated protein kinase C-alpha pseudosubstrate peptide that functions
      as a multidrug resistance reversal agent in human breast cancer cells is not a P
      glycoprotein substrate.
AB  - Protein kinase C-alpha (PKC-alpha) activation is an important contributing factor
      in human breast cancer MCF-7 MDR cell drug resistance. We recently reported the
      use of N-myristoylated PKC-alpha pseudosubstrate peptides with potent PKC-alpha
      inhibitory activity as reversal agents of drug resistance in MCF-7 MDR cells. The
      peptides potently inhibit phosphorylation of the PKC-alpha substrates P
      glycoprotein (P-gp), raf kinase and PKC-alpha itself in MCF-7 MDR cells in
      association with a severalfold induction of intracellular uptake of P-gp
      substrate chemotherapeutics and a statistically significant twofold increase in
      cellular chemosensitivity. We now report that the N-myristoylated PKC-alpha
      pseudosubstrate peptide N-myristoyl-RFARKGALRQKNV (P3) is not a P-gp substrate in
      MCF-7 MDR cells based on a comparison of the cellular uptake of [125I]
      radiolabeled P3 in MCF-7 MDR vs MCF-7 WT cells. The extent of cellular uptake of
      the radiolabeled peptide in the drug-resistant cell line MCF-7 MDR was either
      greater than or equivalent to the uptake in the parental drug-sensitive MCF-7 WT
      cell line over a time course of 30 min to 6 h, and across a peptide concentration
      range of 25-100 microM. Additionally, treatment of the MCF-7 MDR cells with
      verapamil (VPL), a known P-gp efflux inhibitor, had no effect on the cellular
      accumulation of radiolabeled P3. Our results provide direct evidence that the N
      myristoylated pseudosubstrate peptide is taken up equivalently by drug-sensitive
      and MDR cancer cells and therefore has potential value as an MDR reversal agent
      that operates by a novel mechanism.

PMID- 9272126
TI  - Multidrug resistance: molecular mechanisms and clinical relevance.
AB  - Multidrug resistance (MDR) describes the phenomenon of simultaneous resistance to
      unrelated drugs. It has been a decade since the P-glycoprotein (Pgp) gene, which
      is associated with a form of MDR caused by reduced drug accumulation, was cloned.
      Thus, this would seem to be an appropriate time to evaluate our understanding of
      this form of MDR. The two MDR genes identified in humans to date (the MDR
      associated protein [MRP] and Pgp genes) are structurally similar and both are
      members of the ATP-binding cassette (ABC) transporter family. Although the
      physiological role of MRP is not yet understood, one Pgp gene (mdr1) plays an
      important role in the blood-tissue barrier and the other (mdr2/3) is involved in
      phospholipid transport in the liver. A variety of compounds (chemosensitizing
      agents) can interfere with Pgp and MRP function; such agents may improve the
      efficacy of conventional therapy when used in combination with such regimens.
      Determining the roles cellular MDR mechanisms play in patients' response to
      chemotherapy is a major challenge. Using Pgp and MRP as molecular markers to
      detect MDR tumor cells is technically demanding, and solid tumors in particular
      contain heterogeneous cell populations. Since MDR requires Pgp or MRP gene
      expression, clinically relevant gene expression thresholds need to be
      established; sequential samples from individual patients are valuable for
      correlating MDR gene expression with the clinical course of disease. Studies in
      leukemias, myelomas, and some childhood cancers show that Pgp expression
      correlates with poor response to chemotherapy. However, in some cases, inclusion
      of a reversing or chemosensitizing agent such as verapamil or cyclosporin A has
      improved clinical efficacy. Such agents may inactivate Pgp in tumor cells or
      affect Pgp function in normal cells, resulting in altered pharmacokinetics. It
      would be interesting to determine whether patients who fail treatment in the
      presence of chemosensitizing agents acquire other MDR mechanisms. The ABC
      transporter superfamily in prokaryotes and eukaryotes is involved in the
      transport of substrates ranging from ions to large proteins. Of the 15 or more
      ABC transporter genes characterized in human cells, two (Pgp and MRP) cause MDR.
      Therefore, it would be relevant to determine the number of such genes present in
      the human genome; however, extrapolating from the number of ABC transporter genes
      in bacteria, the human gene probably contains a minimum of 200 ABC transporter
      superfamily members. Thus, tumor cells can potentially use many ABC transporters
      to mount resistance to known and future therapeutic agents. The challenge will be
      to determine which ABC transporters are clinically relevant. Despite the
      potential of tumor cells to protect themselves, a variety of malignancies can be
      successfully treated with chemotherapy. This may provide unique insights.

PMID- 9272127
TI  - Design and analysis of trials of salvage therapy in acute myelogenous leukemia.
AB  - Results obtained with a given regimen in relapsed or refractory acute myelogenous
      leukemia (AML) are variable. This often reflects variability in patient
      selection. We have developed a system to account for such variability that
      stratifies patients with refractory or relapsed AML into four groups: group 1,
      first complete response (CR) duration > or = 2 years and receiving first salvage
      treatment (S1); group 2, first CR duration 1-2 years and receiving S1; group 3,
      first CR duration 0-1 years and receiving S1; and group 4, first CR duration 0-1
      years and receiving S2, S3, or S4 after failing S1. CR rates achieved in the four
      groups are 73%, 47%, 14%, and 0, respectively. This system is useful for
      comparing results obtained with different therapies and for assigning patients to
      treatment. At our institution, patients in group 4 are enrolled in phase I
      studies, and phase I1/2-II studies are carried out separately in patients in
      groups 2, 3, and 4. A phase I1/2 study refers to one in which the intent is to
      select for phase II therapies emerging from phase I trial results. The design is
      Bayesian, and although false-negative rates are relatively high, they are lower
      than those obtained if a drug for phase II testing is arbitrarily selected.

PMID- 9272128
TI  - Modulation and prevention of multidrug resistance by inhibitors of P
      glycoprotein.
AB  - Intrinsic and acquired multidrug resistance (MDR) in many human cancers may be
      due to expression of the multidrug transporter P-glycoprotein (Pgp), which is
      encoded by the mdr1 gene. There is substantial evidence that Pgp is expressed
      both as an acquired mechanism (e.g., in leukemias, lymphomas, myeloma, and breast
      and ovarian carcinomas) and constitutively (e.g., in colorectal and renal
      cancers) and that its expression is of prognostic significance in many types of
      cancer. Clinical trials of MDR modulation are complicated by the presence of
      multiple-drug-resistance mechanisms in human cancers, the pharmacokinetic
      interactions that result from the inhibition of Pgp in normal tissues, and, until
      recently, the lack of potent and specific inhibitors of Pgp. A large number of
      clinical trials of reversal of MDR have been undertaken with drugs that are
      relatively weak inhibitors and produce limiting toxicities at doses below those
      necessary to inhibit Pgp significantly. The advent of newer drugs such as the
      cyclosporin PSC 833 (PSC) provides clinicians with more potent and specific
      inhibitors for MDR modulation trials. Understanding how modulators of Pgp such as
      PSC 833 affect the toxicity and pharmacokinetics of cytotoxic agents is
      fundamental for the design of therapeutic trials of MDR modulation. Our studies
      of combinations of high-dose cyclosporin (CsA) or PSC 833 with etoposide,
      doxorubicin, or paclitaxel have produced data regarding the role of Pgp in the
      clinical pharmacology of these agents. Major pharmacokinetic interactions result
      from the coadministration of CsA or PSC 833 with MDR-related anticancer agents
      (e.g., doxorubicin, daunorubicin, etoposide, paclitaxel, and vinblastine). These
      include increases in the plasma area under the curve and half-life and decreases
      in the clearance of these cytotoxic drugs, consistent with Pgp modulation at the
      biliary lumen and renal tubule, blocking excretion of drugs into the bile and
      urine. The biological and medical implications of our studies include the
      following. First, Pgp is a major organic cation transporter in tissues
      responsible for the excretion of xenobiotics (both drugs and toxins) by the
      biliary tract and proximal tubule of the kidney. Our clinical data are supported
      by recent studies in mdr-gene-knockout mice. Second, modulation of Pgp in tumors
      is likely to be accompanied by altered Pgp function in normal tissues, with
      pharmacokinetic interactions manifesting as inhibition of the disposition of MDR
      related cytotoxins (which are transport substrates for Pgp). Third, these
      pharmacokinetic interactions of Pgp modulation are predictable if one defines the
      pharmacology of the modulating agent and the combination. The interactions lead
      to increased toxicities such as myelosuppression unless doses are modified to
      compensate for the altered disposition of MDR-related cytotoxins. Fourth, in
      serial studies where patients are their own controls and clinical resistance is
      established, remissions are observed when CsA or PSC 833 is added to therapy,
      even when doses of the cytotoxin are reduced by as much as 3-fold. This reversal
      of clinical drug resistance occurs particularly when the tumor cells express the
      mdr1 gene. Thus, tumor regression can be obtained without apparent increases in
      normal tissue toxicities. In parallel with these trials, we have recently
      demonstrated in the laboratory that PSC 833 decreases the mutation rate for
      resistance to doxorubicin and suppresses activation of mdr1 and the appearance of
      MDR mutants. These findings suggest that MDR modulation may delay the emergence
      of clinical drug resistance and support the concept of prevention of drug
      resistance in the earlier stages of disease and the utilization of time to
      progression as an important endpoint in clinical trials. Pivotal phase III trials
      to test these concepts with PSC 833 as an MDR modulator are under way or planned
      for patients with acute myeloid leukemias, multiple myeloma, and ovarian
      carcinoma.

PMID- 9272129
TI  - New multidrug-resistance-reversing drugs, MS-209 and SDZ PSC 833.
AB  - The emergence of multidrug resistance (MDR) is a major problem in cancer
      chemotherapy. Many compounds have been developed to reverse MDR, and some of them
      are undergoing clinical trials. Among them, MS-209, a novel quinoline derivative,
      is one of the most potent MDR-reversing agents: MS-209 at 3 microM effectively
      reverses MDR in various cell lines in vitro. MS-209 directly interacts with P
      glycoprotein (Pgp) and inhibits Pgp-mediated drug transport. Oral administration
      of MS-209 combined with anticancer drugs significantly increases the life span of
      mice bearing MDR tumor cells without causing serious side effects. SDZ PSC 833, a
      non-immunosuppressive analogue of cyclosporin A (CsA), is another potent MDR
      reversing drug. Interestingly, the MDR-reversing activity of SDZ PSC 833 is
      enhanced in vitro and in vivo by MRK-16, a monoclonal antibody that recognizes an
      extracellular epitope of Pgp. Since MRK-16 promotes immune responses to MDR tumor
      cells expressing Pgp, the combined use of MRK-16, SDZ PSC 833, and antitumor
      drugs could be an effective therapeutic modality to reverse MDR.

PMID- 9272130
TI  - All-trans retinoic acid significantly increases 5-year survival in patients with
      acute promyelocytic leukemia: long-term follow-up of the New York study.
AB  - All-trans retinoic acid (ATRA) induces a high incidence of complete remission
      (CR) in patients with acute promyelocytic leukemia (APL); however, the magnitude
      of this agent's contribution to increased rates of cure of this disease has not
      yet been established. From 1990 to 1995 we used RA as remission induction therapy
      in 103 APL patients (73 newly diagnosed and 30 previously treated) who were
      retinoid-naive and were treated on the basis of initial morphology. Patients
      whose diagnosis was changed on the basis of the results of molecular testing (n =
      13) were withdrawn from RA treatment and given chemotherapy alone. After
      achieving a CR, previously untreated patients received several cycles of
      consolidation chemotherapy, usually with idarubicin and cytosine arabinoside.
      Among individuals whose diagnosis was molecularly confirmed, 54 of 65 new
      patients (83%) and 25 of 30 previously treated patients (83%) achieved a CR. All
      induction failures in molecularly diagnosed cases were due either to early death
      or to premature withdrawal. Median disease-free and overall survival rates
      recorded for all newly diagnosed patients are currently > 40+ and > 43+ months,
      respectively. We subsequently examined a subset of 27 newly diagnosed patients
      treated during the first 2 years of this program whose actual median follow-up
      period is now > 5 years. Median disease-free and overall survival rates recorded
      for this group are > 57+ and > 58+ months, respectively; 56% of these patients
      are alive in first remission. These results significantly exceed those achieved
      using chemotherapy alone in a historical control group of 80 patients
      consecutively treated at this center from 1975 to 1990, whose median disease-free
      and overall survival rates were 11 and 19 months, respectively; only 22% of these
      patients were alive in first remission at 5 years. Although a high proportion of
      previously treated patients also achieved a CR after RA treatment, median disease
      free and overall survival rates noted for that group were markedly lower (i.e.,
      7.5 and 10.9 months, respectively). Thus, data from patients whose median follow
      up period is now > 5 years have confirmed earlier projections and indicate that
      the use of RA for remission induction yields an approximately 2.5-fold increase
      in the proportion of patients who have presumably been cured of this disease.

PMID- 9272131
TI  - All-trans retinoic acid therapy for newly diagnosed acute promyelocytic leukemia:
      comparison with intensive chemotherapy. The Japan Adult Leukemia Study Group
      (JALSG).
AB  - We analyzed the results of treating patients with newly diagnosed acute
      promyelocytic leukemia (APL) with all-trans retinoic acid (ATRA) in the JALSG AML
      92 study and compared them with those of the AML-87 and AML-89 studies, which
      consisted of standard chemotherapy. In the AML-92 study, patients were scheduled
      to receive 45 mg/ m2 oral ATRA daily until achievement of a complete remission
      (CR). If patients had initial leukocyte counts of > 3.0 x 10(9)/l, they received
      40 mg/m2 daunorubicin (DNR) for 3 days and 200 mg/m2 behenoyl cytarabine (BHAC)
      for 5 days in addition to ATRA. During remission induction therapy, if the
      patients showed peripheral blood myeloblast and promyelocyte counts of > 1.0 x
      10(9)/l, they received additional DNR and BHAC on the same schedule. After
      achievement of a CR, patients received three courses of consolidation and six
      courses of maintenance/intensification chemotherapy. Of 196 evaluable patients,
      173 (88%) achieved a CR: 59 of 62 (95%) treated with ATRA alone, 41 of 49 (84%)
      treated with ATRA plus later chemotherapy, 63 of 73 (86%) treated with ATRA plus
      initial chemotherapy, and 10 of 12 (83%) treated with ATRA plus both initial and
      later chemotherapy. The CR rate in AML-92 was significantly higher than that in
      AML-89, but not than that achieved in AML-87. In addition, the early mortality
      and relapse rates in AML-92 were significantly lower than those in AML-89, but
      were not than those in AML-87. At a median follow-up of 36 months the predicted 4
      year event-free survival (EFS) rate for 196 evaluable patients and the 4-year
      disease-free survival (DFS) rate for the CR cases were 54% and 62%, respectively.
      There was a significant difference in DFS between AML-92 and AML-87 (P = 0.0418)
      but not between AML-92 and AML-89 (P = 0.0687). In contrast, significant
      differences in EFS between AML-92 and both AML-87 (P = 0.0129) and AML-89 (P =
      0.005) were observed. These results suggest that non-cross-resistant therapy
      combined with ATRA and intensive chemotherapy for APL contributes synergistically
      to the significant improvement in EFS.

PMID- 9272132
TI  - New retinoids and arsenic compounds for the treatment of refractory acute
      promyelocytic leukemia: clinical and basic studies for the next generation.
AB  - All-trans retinoic acid (ATRA) is a potent differentiation drug for acute
      promyelocytic leukemia (APL) and is now incorporated into first-line therapy.
      However, ATRA resistance has become a major clinical problem. This limitation has
      prompted the development of alternative agents with desirable pharmacologic
      properties. We describe (1) our recent clinical trial using the new synthetic
      retinoid Am80 to overcome acquired resistance to ATRA and (2) basic in vitro
      effects of arsenic trioxide, a possible alternative to ATRA, on APL cells. A
      total of 19 APL patients who had relapsed after ATRA-induced complete remissions
      (CRs) received 6 mg/m2 Am80 p.o. daily until CR; 11 (58%) patients achieved a CR
      between days 20 and 58 (median day 37). The in vitro sensitivity to Am80, based
      on PML immunostaining, correlated well with the clinical effect in all patients
      tested. All three patients whose blasts were sensitive to Am80 in vitro despite a
      poor response to ATRA achieved CRs. Thus, Am80 might be an effective compound for
      the treatment of refractory APL and is a promising alternative retinoid. Since
      arsenic compounds have reportedly induced CRs in APL patients in China, we
      studied the in vitro effect of arsenic and other metal ions on myeloid leukemia
      cell lines. The effects of arsenic were limited mainly to APL cells, and the
      arsenic concentration was critical for the APL cell line NB4: 1 microM As3+
      induced time-dependent apoptosis, whereas 0.1 microM As3+ allowed partial NB4
      cell differentiation. Arsenic trioxide was equally effective when used on ATRA
      resistant NB4 cells. Among the clinical leukemia samples tested, the in vitro
      cytotoxic effects of As3+ were observed selectively in APL cells, regardless of
      their ATRA sensitivity. These data suggest that APL cells are sensitive to As3+
      and that As3+ acts on APL cells via a different pathway to ATRA.

PMID- 9272133
TI  - Cyclophosphamide, doxorubicin, vincristine, and prednisone versus intensive
      chemotherapy in non-Hodgkin's lymphoma.
AB  - Therapy for aggressive non-Hodgkin's lymphomas has undergone significant
      evolution in the past 25 years. First-generation combination chemotherapy studies
      produced complete response (CR) rates of 45-53% together with 30-37% rates of
      long-term survival. New treatment programs aimed at increasing CR rates were then
      developed on the assumption that the additional patients who achieved a CR would
      become long-term disease-free survivors. Initial reports of single-institution
      pilot studies with third-generation regimens suggested CR and survival rates of
      68-86% and 58-69%, respectively; however, after longer follow-up-periods,
      survival rates decreased. Furthermore, confirmatory national phase II trials
      using these newer regimens produced CR rates of only 49-65% and survival rates of
      50-61%. Thus, ultimate conclusions concerning the efficacy of these new regimens
      awaited the results of prospective randomized trials. The Southwest Oncology
      Group (SWOG) conducted a randomized trial comparing standard therapy. CHOP, to
      the third-generation chemotherapy regimens m-BACOD, ProMACE-CytaBOM, and MACOP-B.
      After 6 years, on difference in the response rate, progression-free survival, or
      overall survival has been found between CHOP and third-generation regimens. For
      example, the 6-year estimates of progression-free survival are CHOP 33%, m-BACOD
      36%, ProMACE-CytaBOM 34%, and MACOP-B 32% (P = 0.41). The 6-year overall survival
      estimates are CHOP 42%, m-BACOD 40%, ProMACE-CytaBOM 46%, and MACOP-B 41% (P =
      0.89). Furthermore, we have not identified any subset of patients who survive
      longer on treatment with the third-generation regimens, and the cost and toxicity
      of the new regimens are higher. On the basis that < 50% of these patients are
      cured, the best approach for any patient is an experimental one designed to
      improve our ability to cure the disease. Examples of this include (1) increasing
      the dose intensity of drugs used in standard regimens and (2) autologous bone
      marrow transplantation and/or peripheral stem-cell support as rescue from marrow
      ablative chemotherapy. If a patient is not eligible or does not wish to
      participate in a clinical trial, CHOP, as inadequate as it is, remains the gold
      standard.

PMID- 9272134
TI  - Treatment for adult T-cell leukemia.
AB  - The purpose of this study was to clarify the clinical efficacy of multidrug
      chemotherapy for aggressive adult T-cell leukemia (ATL). We report the
      therapeutic results of treatment of patients with aggressive ATL undertaken
      between 1986 and 1995. A total of 120 newly diagnosed patients with a performance
      status of 0-3 and aged < 70 years at diagnosis were entered into the study.
      Clinical features, including clinical subtypes, serum levels of lactate
      dehydrogenase and blood urea nitrogen, the response to chemotherapy, and doses of
      individual chemotherapeutic agents, were evaluated. Of the 120 patients enrolled,
      97 had acute-type and 23 lymphoma-type ATL. The complete response rate and median
      survival of these patients were 25.3% and 9 months, respectively. The 2- and 5
      year survival rates were 18.4% and 8%, respectively, and five patients have been
      alive for > 5 years and are disease-free. These long-term survivors had good
      prognostic factors at diagnosis. There was no correlation between the doses of
      the various chemotherapeutic agents and the survival duration. These results
      indicate that ordinary combined chemotherapy has limited ability to improve the
      prognosis of aggressive ATL. Our previous study indicated that expression of P
      glycoprotein in ATL cells might be involved in resistance to chemotherapeutic
      agents, particularly doxorubicin, vincristine, and etoposide. Therefore, new
      therapeutic strategies will be necessary to improve the prognosis of ATL
      patients.

PMID- 9272135
TI  - Phase I/II trial of cure-oriented high-dose chemoradiotherapy with
      transplantation of CD34+ peripheral blood stem cells purified by the
      immunomagnetic bead method for refractory hematological malignancies. Nagoya
      CD34+ PBSCT Study Group.
AB  - A multicenter phase I/II clinical trial was conducted to evaluate the safety of a
      device (Isolex System; Baxter Health Corporation, Irvine, Calif., USA) using the
      immunomagnetic bead method to purify CD34+ stem cells from peripheral blood and
      to assess the efficacy and toxicity of high-dose chemoradiotherapy with
      peripheral blood stem-cell transplantation (PBSCT) using purified CD34+ stem
      cells in patients with refractory hematological malignancies. Patients eligible
      for the study included those who had T-cell acute lymphoblastic leukemia (T-ALL),
      lymphoblastic lymphoma (LBL), mantle-cell lymphoma (MCL), high-risk aggressive
      non-Hodgkin's lymphoma (NHL), and adult T-cell leukemia/lymphoma (ATLL) in first
      complete remission (CR) and those who had standard-risk aggressive NHL, indolent
      lymphoma, Hodgkin's disease, or acute promyelocytic leukemia (APL) in second CR
      or first partial remission (PR) after the completion of first-line chemotherapy
      and were chemosensitive to salvage chemotherapy, in whom tumor contamination of
      harvested peripheral blood stem cells (PBSCs) was possible due to bone marrow or
      peripheral blood involvement. Lack of CD34 expression by tumor cells was an
      important selection factor. Eight patients with hematological malignancies (six
      NHL patients, one ATLL patients, and one APL patient) were enrolled; their median
      age was 41 years (range 26-49 years). After consolidation and mobilization
      chemotherapy, two or three courses of apheresis were performed in each patient.
      After high-dose chemo(radio)therapy, in each patient a median of 1.8 x 10(6)
      cells/kg (range 8.2 x 10(5)-5.1 x 10(6) cells/kg) purified CD34+ PBSCs were
      infused; granulocyte colony-stimulating factor was given from day 1. Median times
      to hematopoietic recovery were as follows: WBC of > or = 1,000/microliter, day
      11; platelet count of > or = 50,000/microliter, day 19; and reticulocyte count of
      > or = 10/1000, day 15. Two NHL patients relapsed at 23 and 9 months after PBSCT,
      respectively; the remaining six patients are alive and in CR. No severe toxicity
      was observed in any patient. Tumor contamination as measured using a polymerase
      chain reaction-mediated RNase protection assay at the 10-4 level was detected in
      the CD34(+)-purified fractions of 2 of the 5 samples analyzed; however, a
      reduction in contaminating lymphoma cells from the autograft of at least 1,000 to
      10,000 orders of magnitude was achieved by CD34+ selection using the
      immunomagnetic bead method. High-dose chemoradiotherapy with transplantation of
      CD34+ PBSCs purified by the immunomagnetic bead method was thus shown to be an
      active and safe therapy for refractory hematological malignancies with bone
      marrow or peripheral blood involvement. However, it is too early for evaluation
      of the long-term survival benefit.

PMID- 9272136
TI  - Importance of dose and dose intensity in the treatment of small-cell lung cancer.
AB  - This review examines the rationale and outcomes of intensive chemotherapy trials
      for small-cell lung cancer (SCLC) to determine whether further clinical research
      in this area is likely to generate improved results. Animal model experiments for
      intensive chemotherapy were reviewed to determine whether results observed in the
      laboratory predicted the outcomes seen in clinical trials. In addition, phase III
      randomized trials that differ only by the quantity of chemotherapy drug delivered
      were examined, with particular attention being paid to whether the conclusions
      reached were consistent when limited-stage and extensive-stage SCLC were
      separately studied. The most clear-cut evidence of benefit in animal model
      experiments comes from models with curative potential. In clinical trials, when
      dose and dose intensity are diminished from standard levels the effect is
      detrimental for both limited- and extensive-stage SCLC. Trials of dose and dose
      intensity above standard levels have not yet shown advantages for patients with
      extensive-stage SCLC. However, the only two randomized trials of chemotherapy
      dose escalation for limited-stage SCLC show statistically significant survival
      benefits. Therefore, animal model experiments have accurately predicted
      conclusions reached in SCLC clinical trials. Future studies of intensive
      chemotherapy for SCLC should focus on the limited-stage group.

PMID- 9272137
TI  - Dose-intensive therapy in lung cancer.
AB  - Lung cancer is epidemic and lethal throughout the world. Overall survival is
      estimated to be 13% at 5 years despite treatment. The use of chemotherapy in
      small-cell lung cancer (SCLC) is established, but it is less active against non
      SCLC (NSCLC). Since 98% of SCLC cases are associated with heavy smoking and
      present at a median age of 60-65 years, the application of dose-intensive therapy
      to lung cancer patients may be complicated by underlying smoking-related
      comorbidity and an enhanced risk for secondary smoking-related malignancies. The
      strategies of intensifying induction therapy, multicycle dose-intensive
      combination therapies, chest radiotherapy, and stem cell purging for both SCLC
      and NSCLC are discussed herein. Limited data regarding high-dose therapy for
      NSCLC have been reported. In SCLC, excellent and immediate palliation is achieved
      through the use of combination chemotherapy. However, by 2 years, only 20-40% of
      limited-disease-(LD) and < 5% of extensive-disease stage (ED) patients remain
      alive. Regimens developed using the many established agents produce similar short
      and long-term outcomes, an observation that suggests that many of our systemic
      agents eradicate the same tumor subpopulation but fail to abolish a central core
      of tumor stem cells, presumably enriched for heterogeneous in vivo resistance
      mechanisms. The identification of these minimal residual tumor (MRT) cells and
      systematic evaluation of their biologic characteristics may guide strategies to
      target these cells specifically; such strategies may include modification of
      chemotherapy, tumor vaccination, or other forms of biologic therapy, such as
      replacement of RB, 3p, and/or p53 function; interference with autocrine or
      paracrine growth loops; or immunologic therapy [interleukin (IL)-2, IL-12,
      immunotoxins, and tumor vaccines], which would be most effective in the setting
      of MRT. To this end the detection of heterogeneity and analysis of patterns of
      coexpression of various markers form the thrust of our MRT detection program. At
      the Dana-Farber Cancer Institute and Beth Israel Hospital we performed stem-cell
      autografts in > 40 patients with LD SCLC and > 25 patients with ED SCLC who were
      in first response to conventional-dose therapy comprising high-dose combination
      alkylating agents. Approximately 80% of our patients were in or near complete
      response after initial chemotherapy. At a minimal follow-up of 23 months (to as
      long as 10 years) after completion of high-dose chemotherapy in our original
      trial, 52% of the patients remain disease-free. Of the ED or extrapulmonary
      patients, approximately 20% remain progression-free at > 2 years after high-dose
      therapy. Local regional recurrence represents about 50% of all relapses. Thus,
      the roles of thoracic radiation dose intensity and purification of stem-cell
      autografts are being evaluated in ongoing trials. It is hoped that a cooperative
      phase III trial testing the concept of dose intensification will begin soon.

PMID- 9272138
TI  - Dose-intensive chemotherapy in extensive-stage small-cell lung cancer.
AB  - The importance of the dose intensity of chemotherapy in achieving maximal
      therapeutic effect has recently been reported for several chemosensitive
      malignant diseases, with Murray et al. reporting that intensive weekly
      chemotherapy using the cisplatin, vincristine, doxorubicin, and etoposide (CODE)
      regimen in small-cell lung cancer (SCLC) is very effective. However, leukopenia
      is the major obstacle to delivering the planned dose in intensive regimens.
      Therefore, we investigated whether recombinant human granulocyte colony
      stimulating factor (rhG-CSF) could allow full drug doses to be given as
      scheduled, thereby improving the final outcome. Extensive-stage (ES) SCLC
      patients were randomized to receive either CODE alone or CODE with rhG-CSF, with
      the CODE regimen consisting of cisplatin given i.v. at 25 mg/m2 weekly for 9
      weeks; vincristine given i.v. at 1 mg/m2 during weeks 1, 2, 4, 6, and 8; and
      doxorubicin given i.v. at 40 mg/m2 and etoposide given i.v. at 80 mg/m2 for 3
      days during weeks 1, 3, 5, 7, and 9, rhG-CSF at 50 micrograms/m2 was given s.c.
      on the days on which cytotoxic drugs were not given. From May 1989 to September
      1991; 64 patients were enrolled in the study, of whom 63 were analyzable (31 for
      CODE alone and 32 for CODE with rhG-CSF). No difference in any of the patients'
      characteristics except gender was found between the two groups. The complete
      response (CR) rate was 34% in the CODE with rhG-CSF group and 23% in the CODE
      alone group; the median survival was 59 and 32 weeks, respectively, in these
      groups (P = 0.004). Therefore CODE with rhG-CSF improved the survival of ES SCLC
      patients. On the basis of these results a phase III study to determine whether
      CODE with rhG-CSF would increase survival as compared to the standard regimen in
      ES SCLC was designed by the Japan Clinical Oncology Group.

PMID- 9272139
TI  - High-dose carboplatin plus paclitaxel with granulocyte colony-stimulating factor
      and peripheral blood stem-cell support in non-small-cell lung cancer.
AB  - The treatment of non-small-cell lung cancer (NSCLC) has recently undergone major
      changes due to the availability of new drugs that demonstrate substantial
      activity in NSCLC patients. Although cure for the majority of stage III NSCLC and
      effectively all stage IV disease patients remains rare, a number of compounds,
      including carboplatin, paclitaxel, docetaxel, irinotecan, and vinorelbine, have
      proved useful in the treatment of these patients. Together with a number of phase
      II trials, phase I trials utilizing escalating doses of carboplatin and
      paclitaxel with growth factor or growth factor and blood stem-cell support have
      shown that substantial increases in dose intensity can be achieved. These studies
      in small numbers of patients have demonstrated that these regimens have
      encouraging activity and have formed the basis of a Cancer and Leukemia Group B
      (CALGB) phase II pilot study. This study will utilize two cycles of high-dose
      carboplatin and Taxol given at an AUC dose of 18 and a 24-h infusion dose of 250
      mg/m2, respectively, with growth factor and stem-cell support to treat stage III
      NSCLC patients. Patients will also receive multimodality therapy, including
      radiation with or without surgery. It is hoped that this effort to intensify
      treatment in patients with limited-stage disease will improve survival and
      benefit the large number of patients with stage III tumors. This paper outlines
      the phase I results that formed the basis of the CALGB trial and reviews several
      recent reports of phase II or phase III trials of single-agent and combination
      regimens for NSCLC.

PMID- 9272140
TI  - High-dose chemotherapy with hematopoietic rescue in breast cancer: from theory to
      practice.
AB  - The development of more effective treatment strategies currently provides the
      only realistic hope of reducing breast cancer mortality. Among such treatments,
      high-dose chemotherapy (HDC) has been proposed to be a potentially curative
      strategy. Consideration of the factors involved in the successful treatment of
      human tumors suggests that HDC could be integrated into the treatment of breast
      cancer, but only if the treatment is adequately planned with regard to tumor
      kinetics and chemotherapy sensitivity and resistance patterns. Two randomized
      studies of the use of HDC in breast cancer have been published recently. In the
      first, HDC using a combination of cyclophosphamide, mitoxantrone, and etoposide
      as initial treatment was compared to a conventional dose regimen consisting of
      cyclophosphamide, mitoxantrone, and vincristine. The second study compared the
      effects of early or delayed HDC in patients who had an optimal response to
      conventional-dose induction chemotherapy. Both studies showed HDC to be more
      effective than conventional-dose treatment in delaying the time to progression,
      but only in the study in which HDC was used as the initial treatment was there an
      effect on survival. The differences between these two investigations can probably
      be explained on the basis of the different effects of the treatment regimens on
      tumor kinetics and the efficiency of HDC when used as salvage therapy in the
      delayed HDC group. Dose-intensive therapy has an established role in breast
      cancer. Attention now needs to focus on methods of optimizing this treatment
      strategy.

PMID- 9272141
TI  - New concepts in the treatment of breast cancer using high-dose chemotherapy.
AB  - High-dose chemotherapy is now frequently used for the treatment of primary and
      metastatic breast cancer. Two recent randomized trials have demonstrated that
      this treatment approach can result in extended disease-free and overall survival
      for patients with metastatic disease. However, treatment results have
      demonstrated that long term remissions from these treatments raise complex
      questions about traditional models of chemotherapy principles. A detailed
      analysis of the principles underlying high-dose therapy is presented in the
      context of principles of dose-response, the inverse rule and the total tumor cell
      kill hypotheses.

PMID- 9272142
TI  - High-dose chemotherapy with autologous hematopoietic stem-cell transplantation in
      breast cancer.
AB  - Since 1981 we have conducted four studies of the treatment of metastatic and
      postoperative high-risk breast cancer with high-dose chemotherapy supported by
      autologous hematopoietic stem-cell transplantation (AHSCT). Study I, involving 56
      metastatic cancer patients, proved that induction chemotherapy produces a lasting
      complete response (CR) in only a few cases despite the achievement of a CR rate
      higher than that expected from standard chemotherapy. Study II was designed to
      examine consolidation chemotherapy in metastatic cancer patients responding to
      induction chemotherapy. At a median follow-up of 26 months (range 2-66),
      consolidation therapy produced a 5-year progression-free survival rate of 27.1%
      in 30 patients showing a CR or a partial response to induction therapy and 58.6%
      in 13 patients showing a CR to consolidation therapy. No treatment-related death
      occurred during study II. The same regimen used in study I was employed for 58
      postoperative high-risk patients in study III. The 10-year disease-free survival
      rate recorded for patients with > or = 10 positive axillary lymph nodes was
      significantly higher (P < 0.05) in the AHSCT-supported chemotherapy group than in
      the conventional chemotherapy group. A double high-dose regimen was adopted for
      21 postoperative high-risk patients in study IV. The 3-year disease-free survival
      rate recorded for 9 patients with > or = 10 positive axillary lymph nodes was
      71.4% at a median follow-up of 25 (range 8-45) months. No treatment-related death
      occurred during study IV. Peripheral blood stem-cell transplantation shortened
      the duration of bone marrow suppression more effectively than did bone marrow
      transplantation, thereby optimizing high-dose chemotherapy.

PMID- 9272143
TI  - Chemotherapy: the more the better? Overview.
AB  - Although numerous clinical trials of high-dose chemotherapy have been performed,
      few have demonstrated that such strategies are statistically significantly better
      than other forms of therapy. Application of dose-intensive and/or high-dose
      chemotherapy should be limited to drug-sensitive tumors, with primary end points
      being increased cure rates or prolonged survival. This should be confirmed by
      randomized clinical trials comparing dose-intensive and/or high-dose chemotherapy
      with standard therapeutic modalities.

PMID- 9272144
TI  - Chemotherapy for small-cell lung cancer: more is not better.
AB  - As have many other chemosensitive tumors, small-cell lung cancer (SCLC) has a
      well-documented chemotherapy dose-response relationship. However, a relationship
      between dose and survival has not yet been established. The effect of dose on
      survival should be examined in terms of both the dose used over a certain period
      (dose intensity) and the total dose of drugs employed, and neither the total dose
      of drugs used nor the duration of maintenance chemotherapy has been proven to
      provide an overall survival benefit. In the case of the dose-intensive approach
      there is no evidence for a significant survival benefit of either high-dose or
      dose-intensive weekly chemotherapy. Stem-cell support may be a promising means of
      increasing dose intensity, but the indications are limited and it should be
      considered highly experimental. Given the relatively good condition of patients
      in most comparative clinical trials, more is not better in chemotherapy for SCLC,
      at least in clinical practice.

PMID- 9272145
TI  - Chemotherapy: the more, the better in malignant lymphoma?
AB  - Several clinical trials have demonstrated that high-dose chemotherapy (HDC) with
      autologous hematopoietic stem-cell transplantation is more effective than
      conventional-dose chemotherapy in some subsets of patients with malignant
      lymphoma, such as relapsed aggressive lymphoma patients showing a response to
      salvage chemotherapy and those with Hodgkin's disease who fail primary initial
      chemotherapy. This paper summarizes recent findings and the following issues
      remaining to be resolved: (1) whether HDC is superior to conventional-dose
      chemotherapy as initial therapy for aggressive lymphoma in unfavorable risk
      groups, (2) whether single HDC or multiple semi-HDC is better, (3) whether HDC
      has curative potential in indolent lymphoma or mantle-cell lymphoma, and (4) the
      HDC regimen that is most useful. To clarify these controversial issues, well
      designed clinical trials are needed. To evaluate whether the concept "the more
      chemotherapy, the better in malignant lymphoma" is valid, the Lymphoma Study
      Group of the Japan Clinical Oncology Group is conducting two kinds of clinical
      trials in high- and high-intermediate-risk aggressive lymphoma patients, focusing
      on the dose intensity of key agents. One is a randomized phase II trial of dose
      escalated cyclophosphamide, doxorubicin, vincristine, and prednisolone (high
      CHOP) versus shortened CHOP (biweekly CHOP) with prophylactic use of granulocyte
      colony-stimulating factor. The other is a phase II trial of HDC with peripheral
      blood stem-cell transplantation as a part of the initial therapy. If promising
      results are obtained from these trials a randomized phase III trial will be
      considered to compare the best dose-intensive regimen with standard CHOP.

PMID- 9272146
TI  - Pharmacological considerations in high-dose chemotherapy.
AB  - Recent advances in pharmacokinetic/pharmacodynamic analysis have been applied to
      the development of anticancer agents. In addition, there has been an increase in
      the interest in pharmacokinetic/pharmacodynamic analysis in relation to the field
      of high-dose (HD) chemotherapy. The basis for investigation of the concept of the
      dose-response relationship in HD should be the "exposure-response relationship",
      this can be investigated in phase I and pharmacology trials of HD chemotherapy
      designed to define the relationship between escalation of the target drug dose
      and exposure. Whether pharmacokinetics are linear or nonlinear is important in
      the determination of optimal dosing. Nonhematological toxicities have become more
      important than hematological toxicities as pharmacodynamic parameters in HD
      chemotherapy; however, the relationship between drug exposure and the clinical
      outcome remains unclear. Cellular concentration and plasma exposure are important
      predictors of clinical effect. Wide interpatient pharmacokinetic or exposure
      variability is more important in HD chemotherapy than in conventional-dose
      chemotherapy due to the increase in the frequency and severity of
      nonhematological toxicities. Drug-drug interactions are also important issues in
      HD chemotherapy, although definitive evidence is difficult to obtain. Future
      investigations of HD chemotherapy are warranted on the basis of
      pharmacokinetic/pharmacodynamic analysis.

PMID- 9272148
TI  - Identical mutations and phenotypic variation.
AB  - The relationship between pathogenetic mutations and disease phenotype is becoming
      increasingly complex. Well-delineated clinical entities can be genetically
      heterogeneous, and mutations in a particular gene may result in fundamental
      clinical differences. Genetic heterogeneity includes mutations at different gene
      loci or allelic mutations within a single gene, resulting in a similar phenotype.
      However, one and the same mutation is expected to be associated with a uniform
      clinical picture. In the present article, evidence is presented that this is not
      necessarily the case, and examples of identical mutations resulting in highly
      variable combinations of clinical features are discussed. Although the number of
      examples of this puzzling phenomenon is rapidly increasing, the underlying
      mechanisms are as yet poorly understood. In some cases, interacting genetic
      alterations can be held responsible for the phenotypic heterogeneity; in others,
      epigenetic phenomena provide a plausible explanation. These and other mechanisms
      under discussion are considered here. The Mendelian concept of monofactorial
      disease causation appears to be increasingly untenable for a growing number of
      developmental errors.

PMID- 9272147
TI  - Human centromeric DNAs.
AB  - Human centromeres have been extensively studied over the past two decades.
      Consequently, more is known of centromere structure and organization in humans
      than in any other higher eukaryote species. Recent advances in the construction
      of a human (or mammalian) artificial chromosome have fostered increased interest
      in determining the structure and function of fully functional human centromeres.
      Here, we present an overview of currently identified human centromeric repetitive
      DNA families: their discoveries, molecular characterization, and organization
      with respect to other centromeric repetitive DNA families. A brief examination of
      some functional based studies is also included.

PMID- 9272149
TI  - Localisation of the classical DNA satellites on human chromosomes as determined
      by primed in situ labelling (PRINS).
AB  - The chromosomal localisation and relative amounts in humans of the classical DNA
      satellites I, II and III have been determined by using the primed in situ
      labelling reaction with a variety of oligonucleotide primers. The centromeres of
      seven of the human chromosomes, viz. nos 6, 8, 11, 12, 18, 19 and X, are not
      identifiably marked by any of the primers. A possible phylogenetic explanation of
      this is suggested and the possible relationship of the classical satellites to
      the function of the centromere is discussed.

PMID- 9272150
TI  - Interaction between obesity and genetic polymorphisms in the apolipoprotein CIII
      gene and lipoprotein lipase gene on the risk of hypertriglyceridemia in Chinese.
AB  - To understand the effects of the interaction between genetic polymorphisms and
      obesity on the risk of hypertriglyceridemia (HTG), two polymorphisms, an SstI
      polymorphism on the apolipoprotein CIII gene and a HindIII polymorphism on the
      lipoprotein lipase gene, were analyzed in 339 Chinese subjects with (82 cases in
      the HTG group) or without HTG (257 cases in the control group). Our data revealed
      that the frequencies of obesity, the SstI minor allele (S2), and the HindIII
      major allele (H+) in the HTG group were significantly higher than in the control
      group. Subgroup analysis revealed that the association between these two
      polymorphisms and HTG occurred predominantly in nonobese subjects and in subjects
      with the less hypertriglyceridemic genotype of another polymorphism. Multivariate
      logistic regression analysis showed that all three risk factors (obesity, S2
      containing chromosome, and H+ homozygosity) were associated with HTG, and an
      interaction was found between obesity and H+ homozygosity for the occurrence of
      HTG. The risk of HTG increased significantly with combinations of risk factors.
      Subjects can be divided into low or high risk groups for HTG using such
      combinations. These results provide evidence of interaction between obesity and
      the HindIII polymorphism of the lipoprotein lipase gene on the risk of HTG.

PMID- 9272151
TI  - A de nevo complex t(7;13;8) translocation with a deletion in the TRPS gene
      region.
AB  - Molecular cytogenetic analyses have resolved the pathogenetic aberration of an 8
      year-old girl with tricho-rhino-phalangeal syndrome type I (TRPS I), normal
      intelligence, and a karyotype originally described as 46,XX,t(8;13)(q24;q21). R-
      and Q-banding and high resolution R-banding analyses have also disclosed a
      seemingly mosaic abnormality of the distal short arm of chromosome 7 but have not
      fully characterized this abnormality. Combined primed in situ labelling and
      chromosome painting, and three-colour chromosome painting have revealed a
      complex, apparently balanced translocation t(7;13;8). Fluorescence in situ
      hybridization with yeast artificial chromosome and cosmid clones from 8q24.1 has
      shown an interstitial deletion of at least 3 Mb covering most of the TRPS I
      critical region.

PMID- 9272152
TI  - CAG repeat analyses in frozen and formalin-fixed tissues following primer
      extension preamplification for evaluation of mitotic instability of expanded SCA1
      alleles.
AB  - Neurodegenerative disorders, including spin-ocerebellar ataxias (SCA), Huntington
      disease (HD) and dentatorubral-pallidoluysian atrophy (DRPLA), are associated
      with unstable CAG repeats. To investigate the mitotic stability of the repetitive
      element in the genes for SCA1, SCA3, HD, and DRPLA we extracted DNA from up to 13
      tissue samples from four deceased individuals with progressive neurological
      disorders and neuropathological signs. Due to the formalin fixation of some
      tissues the genomic DNA was highly degraded and unsuitable for amplification of
      fragments longer than 150 bp. After size selection and primer extension
      preamplification, specific analyses could be performed even for expanded alleles.
      In all four patients the SCA1 mutation could be demonstrated, in one case with
      remarkable somatic heterogeneity of the elongated allele, whereas alleles of the
      normal range were stable in all tissues examined.

PMID- 9272153
TI  - Loss of the PLA2G2A gene in a sporadic colorectal tumor of a patient with a
      PLA2G2A germline mutation and absence of PLA2G2A germline alterations in patients
      with FAP.
AB  - The Min (multiple intestinal neoplasia) mouse with a germline mutation in the
      adenomatous polyposis coli gene serves as an animal model for familial
      adenomatous polyposis coli (FAP). The number and age at onset of colorectal
      adenomas varies in the offspring of Min mice crossed with other strains. The
      murine gene for the secretory phospholipase A2 (PLA2G2A) was found to be the main
      candidate for these variations. To test the hypothesis of a correlation between
      PLA2G2A gene alterations and human tumor development, we screened 14 patients
      with FAP and 20 patients with sporadic colorectal cancer for germline and somatic
      PLA2G2A gene mutations. None of the individuals with FAP showed PLA2G2A germline
      alterations. However, a germline mutation was observed in one patient with an
      apparently sporadic colorectal tumor; the wildtype allele was somatically lost in
      the tumor of this patient.

PMID- 9272154
TI  - The STR252-IVS10nt546-VNTR7 phenylalanine hydroxylase minihaplotype in five
      Mediterranean samples.
AB  - IVS10nt546 (IVS10nt-11g-->a) is the most common molecular defect of the
      phenylalanine hydroxylase gene causing phenylketonuria in Mediterranean
      populations. Previous studies have proposed various and alternative hypotheses
      concerning the geographical origin and pattern of diffusion of this mutation in
      this area. In this study, this issue was re-examined on a large sample (149) of
      "Mediterranean" IVS10nt546 mutant alleles analysed with multiallelic intragenic
      polymorphisms. The analysis of intragenic microsatellite (STR) and minisatellite
      (VNTR) polymorphisms shows allelic heterogeneity of the IVS10nt546 mutation.
      Eight STR and three VNTR alleles were found in association with the splicing
      defect. Of the ten detected STR-VNTR combinations ("minihaplotypes"), we
      identified a predominant allelic association (VNTR7-STR252) embedded in a RFLP
      haplotype 6 background, which seems to correspond to the ancestral gene
      originating in the Turkey-Israel area. Analysis of both absolute and relative
      gene frequencies of the STR252-IVS10nt546-VNTR7 minihaplotypes, shows
      statistically significant (P < 0.02) variations and may suggest gene flow from
      Turkey and/or Israel to Italy and Spain. The associated migratory events need not
      be unique in time (and people) but seem to suggest they may be traced back to the
      expansion of the Neolithic culture and people, thus allowing dating of the origin
      of this mutation to at least 5000-10000 years ago. Alternative hypotheses are
      discussed to explain, in light of the available historical and pre-historical
      evidence, the pattern of diffusion of the IVS10nt546 mutation in the
      Mediterranean basin.

PMID- 9272155
TI  - The long QT syndrome: a novel missense mutation in the S6 region of the KVLQT1
      gene.
AB  - The Romano Ward long QT syndrome (LQTS) has an autosomal dominant mode of
      inheritance. Patients suffer from syncopal attacks often resulting in sudden
      cardiac death. The main diagnostic parameter is a prolonged QT(c) interval as
      judged by electro-cardiographic investigation. LQTS is a genetically
      heterogeneous disease with four loci having been identified to date: chromosome
      11p15.5 (LQT1), 7q35-36 (LQT2), 3p21-24 (LQT3) and 4q25-26 (LQT4). The
      corresponding genes code for potassium channels KVLQT1 (LQT1) and HERG (LQT2) and
      the sodium channel SCN5A (LQT3). The KVLQT1 gene is characterized by six
      transmembrane domains (S1-S6), a pore region situated between the S5 and S6
      domains and a C-terminal domain accounting for approximately 60% of the channel.
      This domain is thought to be co-associated with another protein, viz. minK
      (minimal potassium channel). We have studied a Romano Ward family with several
      affected individuals showing a severe LQTS phenotype (syncopes and occurrence of
      sudden death). Most affected individuals had considerable prolongations of QT(c).
      By using haplotyping with a set of markers covering the four LQT loci, strong
      linkage was established to the LQT1 locus, whereas the other loci (LQT2, LQT3 and
      LQT4) could be excluded. Single-strand conformation polymorphism analysis and
      direct sequencing were used to screen the KVLQT1 gene for mutations in the S1-S6
      region, including the pore domain. We identified a Gly-216-Arg substitution in
      the S6 transmembrane domain of KVLQT1. The mutation was present in all affected
      family members but absent in normal control individuals, providing evidence that
      the mutated KVLQT1-gene product indeed caused LQTS in this family. The mutated
      KVLQT1-gene product thus probably results in a dominant negative suppression of
      channel activity.

PMID- 9272156
TI  - Hereditary nonpolyposis colorectal cancer: causative role of a germline missense
      mutation in the hMLH1 gene confirmed by the independent occurrence of the same
      somatic mutation in tumour tissue.
AB  - Evaluation of the causative role of germline mutations in DNA mismatch repair
      genes in hereditary nonpolyposis colorectal cancer (HNPCC) families can be
      difficult. Whereas nonsense, frameshift or splice-site mutations are presumed to
      lead to dysfunctional gene products and thus are generally considered to be
      causative, the evaluation of missense mutations often remains uncertain. We
      observed a novel germline mutation in the hMLH1 gene (His-->Pro at codon 329) in
      an HNPCC family. The same missense mutation also occurred as a somatic event in
      the colonic tumours of two other HNPCC patients who had germline mutations at
      different sites of the hMLH1 gene. Thus, the H329P mutation present in the
      germline can be considered as having an aetiological role in this HNPCC family.

PMID- 9272157
TI  - Distinct spectrum of CFTR gene mutations in congenital absence of vas deferens.
AB  - Congenital absence of the vas deferens (CAVD) is a frequent cause for obstructive
      azoospermia and accounts for 1%-2% of male infertility. A high incidence of
      mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene
      has recently been reported in males with CAVD. We have investigated a cohort of
      106 German patients with congenital bilateral or unilateral absence of the vas
      deferens for mutations in the coding region, flanking intron regions and promotor
      sequences of the CFTR gene. Of the CAVD patients, 75% carried CFTR mutations or
      disease-associated CFTR variants, such as the "5T" allele, on both chromosomes.
      The distribution of mutation genotypes clearly differed from that observed in
      cystic fibrosis. None of the CAVD patients was homozygous for delta F508 and none
      was compound heterozygous for delta F508 and a nonsense or frameshift mutation.
      Instead, homozygosity was found for a few mild missense or splicing mutations,
      and the majority of CAVD mutations were missense substitutions. Twenty-one German
      CAVD patients were compound heterozygous for delta F508 and R117H, which was the
      most frequent CAVD genotype in our study group. Haplotype analysis indicated a
      common origin for R117H in our population, whereas another frequent CAVD
      mutation, viz. the "5T allele" was a recurrent mutation on different intragenic
      haplotypes and multiple ethnic backgrounds. We identified a total of 46 different
      mutations and variants, of which 15 mutations have not previously been reported.
      Thirteen novel missense mutations and one unique amino-acid insertion may be
      confined to the CAVD phenotype. A few splice or missense variants, such as F508C
      or 1716 G-->A, are proposed here as possible candidate CAVD mutations with an
      apparently reduced penetrance. Clinical examination of patients with CFTR
      mutations on both chromosomes revealed elevated sweat chloride concentrations and
      discrete symptoms of respiratory disease in a subset of patients. Thus, our
      collaborative study shows that CAVD without renal malformation is a primary
      genital form of cystic fibrosis in the vast majority of German patients and links
      the particular expression of clinical symptoms in CAVD with a distinct subset of
      CFTR mutation genotypes.

PMID- 9272158
TI  - Progressive familial intrahepatic cholestasis (PFIC): evidence for genetic
      heterogeneity by exclusion of linkage to chromosome 18q21-q22.
AB  - Progressive familial intrahepatic cholestasis (PFIC) is the second most common
      form of familial intrahepatic cholestasis. The genes for PFIC and for a milder
      form of the disease, benign recurrent intrahepatic cholestasis (BRIC), were
      recently mapped to a 19-cM region on chromosome 18q21-q22. The results suggest
      that PFIC and BRIC are allelic diseases. We have studied 11 Swedish patients from
      eight families with clinical and biochemical features consistent with PFIC. The
      families were genotyped for markers D18S69, D18S64, D18S55 and D18S68, spanning
      the PFIC candidate region. Unexpectedly, the segregation of haplotypes excluded
      the entire region in three families, and no indications for shared haplotypes
      were found in the patients of the six remaining families. A four-point linkage
      analysis of all families excluded linkage from D18S69 to D18S55 (Zmax < -5).
      Thus, our data strongly suggest the presence of a second, yet unknown, locus for
      PFIC. The results indicate that great care should be taken when using 18q markers
      for prenatal diagnosis and genetic counseling for the disease.

PMID- 9272159
TI  - Benign recurrent intrahepatic cholestasis (BRIC): evidence of genetic
      heterogeneity and delimitation of the BRIC locus to a 7-cM interval between
      D18S69 and D18S64.
AB  - Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive liver
      disease characterized by multiple episodes of cholestasis without progression to
      chronic liver disease. The gene was previously assigned to chromosome 18q21,
      using a shared segment analysis in three families from the Netherlands. In the
      present study we report the linkage analysis of an expanded sample of 14 BRIC
      families, using 15 microsatellite markers from the 18q21 region. Obligate
      recombinants in two families place the gene in a 7-cM interval, between markers
      D18S69 and D18S64. All intervening markers had significant LOD scores in two
      point linkage analysis. Moreover, we identified one family in which the BRIC gene
      seems to be unlinked to the 18q21 region, or that represents incomplete
      penetrance of the BRIC genotype.

PMID- 9272160
TI  - Supernumerary nipples occurring together with Becker's naevus: an association
      involving one common paradominant trait?

PMID- 9272161
TI  - Screening for connexin 32 mutations in Charcot-Marie-Tooth disease families with
      possible X-linked inheritance.
AB  - The X-linked dominant form of Charcot-Marie-Tooth disease (CMTX) is associated
      with mutations in a gene coding for the gap-junction protein connexin 32 (Cx32).
      We screened 32 CMT families with a pedigree pattern suggestive of X-linked
      inheritance for the presence of mutations in the coding region of Cx32 by direct
      sequencing. Five of the families had a CMT1 diagnosis, 24 had a CMT2 diagnosis
      and 3 patients had an unspecified CMT. Eight families with a Cx32 point mutation
      were detected. Five different mutations (four of them published previously) were
      found in six CMT2 families and one mutation was found in a sporadic CMT1 male
      patient. One of the mutations, Met194Val, is among the first described in the
      fourth transmembrane domain of Cx32. Two CMT2 families and the sporadic CMT1
      patient had the same mutation, Arg22Gln. An additional, previously unpublished
      mutation, Arg75Trp, was found in a male patient with unspecified CMT, who
      subsequently was verified to have a variant Klinefelter syndrome with 48,XXYY
      karyotype. Our findings show the difficulty in distinguishing CMTX patients from
      CMT1 and CMT2 patients, and they emphasize the need for Cx32 mutation screening
      in families previously diagnosed with CMT2.

PMID- 9272162
TI  - Localization of a novel human RNA-editing deaminase (hRED2 or ADARB2) to
      chromosome 10p15.
AB  - RNA-editing deaminase 2 (RED2; ADARB2) is a newly identified potential double
      stranded RNA adenosine deaminase. It is the third member of this family, which
      includes DRADA and RED1. Genes of this family are candidates for involvement in
      neurological diseases such as epilepsy, because of their expression patterns and
      described functions. All three described genes are well expressed in brain, and
      DRADA and RED1 have been shown to play a role in the editing of mRNAs coding for
      glutamate receptor subunits in vitro, thereby changing the properties of these
      channels, which are the main excitatory neurotransmitter receptors in brain. Here
      we report the mapping of the human RED2 (hRED2; ADARB2) gene. Using the sequence
      of rat RED2, we identified a homologous human expressed sequence tag, and
      subsequently designed primers in the 3' untranslated region of the hRED2
      transcript to perform polymerase chain reaction amplification on two somatic cell
      hybrid mapping panels. This allowed us to localize hRED2 on chromosome 10p15;
      until now, no genetic diseases have been mapped in this region or in the syntenic
      mouse chromosomal region that may involve RED2.

PMID- 9272163
TI  - Detection of chromosomal aneuploidy in endometriosis by multi-color fluorescence
      in situ hybridization (FISH).
AB  - Endometriosis affects 10-15% of women of reproductive age and is a common cause
      of infertility and pelvic pain. Although endometriosis is characterized by
      abnormal growth or turn-over of cells, the genetic changes involved remain
      unclear. We employed a multi-color fluorescence in situ hybridization (FISH)
      strategy to determine the incidence of somatic chromosomal numeric alterations in
      severe/late stage endometriosis. Using alpha-satellite sequence-specific DNA
      probes for chromosomes 7, 8, 11, 12, 16, 17, and 18, simultaneous two- and three
      color FISH were performed to evaluate the frequency of monosomic, disomic, and
      trisomic cells in normal control and endometriotic tissue specimens. In one of
      four endometriosis samples studied, a significantly higher frequency of monosomy
      for chromosome 17 (14.8%, chi 2(4) = 53.3, P < 0.0001) and 16 (8.8%, chi 2(4) =
      11.4, P < 0.05) was observed. An increased number of cells with chromosome 11
      trisomy (14.8%, chi 2(4) = 96.2, P < 0.0001) were detected in a second case. In a
      third case, a distinct colony of nuclei with chromosome 16 monosomy (14.1%, chi
      2(4) = 21.39, P < 0.005) was detected. Acquired chromosome-specific aneuploidy
      may be involved in endometriosis, reflecting clonal expansion of chromosomally
      abnormal cells. That candidate tumor suppressor genes and oncogenes have been
      mapped to chromosomes 11, 16, and 17 suggests that chromosomal loss or gain plays
      a role in the development and/or progression of endometriosis.

PMID- 9272164
TI  - Trinucleotide repeats (CGG)22TGG(CGG)43TGG(CGG)21 from the fragile X gene remain
      stable in transgenic mice.
AB  - Unstable premutation alleles in fragile X contain CGG repeats ranging from 34 to
      about 200. To study the mechanism of formation and the behavior of dynamic
      mutations, we constructed and cloned 88 trinucleotide repeats including 43
      uninterrupted CGGs and injected them into mouse fertilized oocytes. We analyzed
      342 transgenic animals obtained from 6 different founders after one to four
      generations, and found that the repeats remained stable regardless of the sex of
      the transmitting mouse. Therefore, we may need to consider factors other than
      trinucleotide repeat length alone to explain CGG instability and create an animal
      model.

PMID- 9272165
TI  - Molecular studies in 37 Silver-Russell syndrome patients: frequency and etiology
      of uniparental disomy.
AB  - We report studies on the etiology of uniparental disomy (UPD) in Silver-Russell
      syndrome (SRS) patients. Thirty-seven SRS families were typed with short tandem
      repeat markers from chromosomes 2, 7, 9, 14, and 16. UPD for these chromosomes
      has either been described in association with growth retardation or has been
      observed in confined placental mosaicism, a mechanism that may result in UPD.
      Maternal UPD7 was detected in three SRS patients, accounting for approximately
      10% of the tested SRS patients. These results agree with previously published
      studies. The allelic distribution in one of the three families indicates complete
      isodisomy, whereas allelic patterns in the other two families are consistent with
      partial and complete heterodisomy, respectively, suggesting that, in the latter
      cases, UPD originates from maternal meiosis, whereas in the first case, it seems
      to be of mitotic origin. STR typing for UPD of chromosomes 2, 9, 14, and 16
      showed no abnormalities. Our results demonstrate the necessity of screening SRS
      patients for UPD7, although the effect of UPD7 cannot be correlated with the SRS
      phenotype as yet. An association between UPD for the other investigated
      chromosomes and SRS seems to be negligible.

PMID- 9272166
TI  - Angiotensin-converting enzyme (ACE) gene polymorphisms in patients characterised
      by coronary angiography.
AB  - The angiotensin converting enzyme (ACE) gene is implicated as a risk factor for
      coronary artery disease and myocardial infarction (MI). An insertion/deletion
      (I/D) polymorphism is believed to be in linkage disequilibrium with a functional
      site elsewhere. Ten polymorphisms have recently been identified in the ACE gene.
      We screened patients undergoing coronary angiography (n = 258) for six of these
      polymorphisms (T-5491C, T-93C, A-240T, T1237C, D/I and 4656(CT)2/3), and
      identified a further two rare polymorphisms. ACE levels were associated with
      genotype for all polymorphisms analysed individually by one way ANOVA (P <
      0.0005). The polymorphisms occurring in the 5' region were in negative linkage
      disequilibrium with the exonic and 3' region polymorphisms. The A-240T
      polymorphism had the greatest association with ACE levels (R2 = 14%); none of the
      others were significantly associated with levels when adjustment was made for A
      240T. None of the polymorphisms were associated with the extent of coronary
      atheroma. Two of the promoter polymorphisms (A-240T and T-93C) were weakly
      related to the occurrence of MI (P = 0.03 and P = 0.05, respectively, by chi 2
      analysis). The TT genotype of A-240T appeared to be protective against MI with an
      odds ratio of 0.31 (95% confidence interval, 0.12, 0.83). These findings indicate
      that polymorphisms in the ACE gene promoter region may have a stronger
      association with disease than the I/D polymorphism.

PMID- 9272167
TI  - Localization of the gene for Wieacker-Wolff syndrome in the pericentromeric
      region of the X chromosome.
AB  - The Wieacker-Wolff syndrome (WWS, MIM* 314580), first described clinically in
      1985, is an X-linked recessive disorder. In earlier studies, linkage between the
      WWS gene and DXYS1 at Xq21.2 and DXS1 at Xq11 as well as AR at Xq12 was reported.
      Here we report on a linkage analysis using highly polymorphic, short terminal
      repeat markers located in the segment from Xp21 to Xq24. No recombination between
      the WWS locus and ALAS2 or with AR (z = 4.890 at theta = 0.0) was found.
      Therefore, the WWS locus was assigned to a segment of approximately 8 cM between
      PFC (Xp11.3-Xp 11.23) and DXS339 (Xq11.2-Xq13).

PMID- 9272168
TI  - Chromosomal instability in a woman with infertility and two unaffected brothers:
      a new familial chromosomal breakage syndrome?
AB  - Repeated chromosomal analysis of peripheral blood lymphocytes and skin
      fibroblasts from a woman referred for amenorrhoea, streak gonads,
      hyperthyroidism, adiposity and elevated alpha-fetoprotein levels but no other
      manifestations of known chromosomal breakage syndromes demonstrated an increased
      spontaneous chromosomal breakage rate (ISCBR). Chromatid and chromosomal breaks
      were more numerous than sporadic rearrangements and dicentric chromosomes.
      Exposure of the cells to mitomycin C, diepoxybutane, X-rays or UV irradiation
      induced an increase in chromosomal and chromatid abnormalities over that in
      controls. A micronucleus assay demonstrated an increase in the incidence of
      formation of micronuclei and the population doubling time of the fibroblasts of
      the proposita was delayed. Chromosomal analysis was performed on lymphocytes of
      the parents and of five sibs of the proposita. Two brothers had chromosomal
      abnormalities identical to those of the patient and elevated alpha-fetoprotein
      levels, however, without any clinical abnormalities. The parents were affected by
      only a moderate ISCBR whereas two brothers and one sister were chromosomally
      normal. The clinical, chromosomal and biochemical findings in this family
      represent a novel chromosomal instability syndrome.

PMID- 9272169
TI  - Molecular cloning of the breakpoints of the hereditary persistence of fetal
      hemoglobin type-6 (HPFH-6) deletion and sequence analysis of the novel juxtaposed
      region from the 3' end of the beta-globin gene cluster.
AB  - Naturally occurring deletion mutations within the human beta-globin cluster lead
      to specific, phenotypically discrete syndromes (i.e., delta beta-thalassemias and
      hereditary persistence of fetal hemoglobin, HPFH), characterized by increased
      production of fetal hemoglobin in adult life. We have previously characterized an
      enhancer element, which is juxtaposed to the fetal G gamma-gene, by means of a
      deletion first described in a Thai family. To obtain further insights into the
      mechanisms involved in this deletion, we have now characterized several of its
      novel features. Following amplification by the polymerase chain reaction and
      sequencing of the 1.5-kb bridging fragment, we have shown that the 5' breakpoint
      of the deletion occurs 1260 bp 3' of the fetal G gamma-globin gene, whereas the
      3' breakpoint lies 521 bp upstream of the EcoRI site of the enhancer element and
      2845 bp upstream of the 3' breakpoint of the Chinese (A gamma delta beta) zero
      thalassemia deletion. The total length of the deletion is 101 kb, which resembles
      that of HPFH-1 and HPFH-2 deletions and a set of two gamma delta beta-thalassemia
      deletions. Our data further support the hypothesis that these sets of large
      deletions with almost identical lengths are generated via the loss of a complete
      chromatin loop. To elucidate further the mechanisms leading to the deletion, we
      have sequenced the novel 0.5-kb region residing immediately 3' to the breakpoint
      and shown that it contains putative binding sites for several transcription
      factors, such as HNF-1, AP-1, and TFIID. Sequence comparison of the deletion
      breakpoints reveals no junctional homology, indicating an end-to-end joining of
      blunted ends; a pair of 7-nt complementary repeats adjacent to a set of a direct
      CCCT repeat flanks the breakpoints. This limited homology constitutes a frequent
      characteristic of a non-homologous recombination mechanism. All these features of
      the HPFH-6 deletion suggest that this mutation has resulted from a non-homologous
      recombination event.

PMID- 9272170
TI  - Quantification of the paternal allele bias for new germline mutations in the
      retinoblastoma gene.
AB  - New germline mutations in the human retinoblastoma gene are known to arise
      preferentially on paternally derived chromosomes, but the magnitude of that bias
      has not been measured. We evaluated 49 cases with a new germline mutation and
      found that in 40 cases (82%) the mutation arose on the paternally derived allele.
      We also evaluated 48 cases likely to have a somatic initial mutation; in this
      group the initial mutation arose on paternal or maternal chromosomes with
      approximately equal frequency. There was no statistically significant difference
      in the average age of fathers of children with new paternal germline mutations
      from the average age of fathers of children with new maternal germline mutations
      or somatic initial mutations. Combining the data with that from previous reports
      from other groups, the proportion of new germline mutations arising on a
      paternally derived allele is 85% (based on 72 cases; 95% confidence interval = 76
      93%). This number can be useful in the genetic counseling of some families with
      retinoblastoma.

PMID- 9272171
TI  - Adult onset globoid cell leukodystrophy (Krabbe disease): analysis of
      galactosylceramidase cDNA from four Japanese patients.
AB  - We examined galactosylceramidase (GALC) cDNA in four Japanese patients with adult
      onset globoid cell leukodystrophy (Krabbe disease; AO-GLD) by polymerase chain
      reaction/single-strand conformation polymorphism (PCR-SSCP) analysis, subsequent
      sequence determination, and restriction enzyme digestion of PCR products, initial
      symptoms were the onset of slowly progressive spastic paraplegia from the middle
      of the second decade, and all patients had diminished GALC activity in their
      leukocytes. We identified three missense mutations (I66M, G270D, L618S) and one
      exon-6 skipping (535-573del). Two of the patients had only the I66M mutant mRNA,
      and one only the G27OD mutant mRNA. The fourth patient carried a compound
      heterozygous mutation of 535-573del and L618S. To determine the enzymatic
      activities produced by these mutations, we constructed mutated GALC cDNAs and
      expressed them in COS-1 cells. Three mutations, viz., G270D, L618S, and exon-6
      skipping (535-573del), produced diminished GALC activity as expected. The I66M
      mutation in the wild-type GALC cDNA(I289) had normal activity, but when this
      mutation and the V289 polymorphism were introduced into the same allele, it had
      decreased activity. Thus, the combination of a unique mutation and polymorphism
      causes conformational change in the GALC enzyme, resulting in low enzymatic
      activity. AO-GLD mutations, including those found here, are located in the N
      terminus (I66M, G270D, 535-573del) or C-terminus (L618S) of the GALC enzyme,
      whereas the reported mutations in the infantile form (IF-GLD) are in the central
      domain. This difference in mutation sites may affect the clinical features of
      GLD.

PMID- 9272172
TI  - Human transferrin (Tf): a single mutation at codon 570 determines Tf C1 or Tf C2
      variant.
AB  - Transferrin (Tf) has many variants, as revealed by isoelectric focusing (IEF).
      Although these Tf variants have long been thought to arise from the multiple
      alleles at single Tf locus, amino acid substitution related to the two major
      variants, Tf C1 and Tf C2, has so far not been reported. We investigated the
      difference responsible for Tf C1 and Tf C2 variants and identified a single base
      change in exon 15 of the Tf gene resulting in the phenotypes on IEF. C/T base
      substitution at codon 570 replaced Pro in Tf C1 with Ser in Tf C2. Based on this
      nucleotide substitution, we established PCR-based genotyping for the Tf C1 and Tf
      2 alleles.

PMID- 9272173
TI  - Evidence that skewed X inactivation is not needed for the phenotypic expression
      of Aicardi syndrome.
AB  - Aicardi syndrome is a rare disorder characterized by absent corpus callosum,
      infantile spasms, and choriorentinal lacunae. It is sporadic in nature and
      affects only females, resulting in severe mental and physical handicap. It has
      been suggested that the disease is caused by a dominant X-linked mutation which
      occurs de novo in females, and is lethal in hemizygous male embryos. This mode of
      inheritance has been observed in a number of other rare syndromes. In these
      syndromes, when X inactivation is studied, a non-random pattern is usually found.
      We have studied the X inactivation pattern in ten female patients with Aicardi
      syndrome and their parents using the highly polymorphic, differentially
      methylated androgen receptor gene. The results showed an unexpected random X
      inactivation pattern in these patients. Previous clinical and cytogenetic
      evidence suggests that Aicardi syndrome is caused by an X-linked dominant
      mutation, de novo in females and lethal in males. However, unlike most other
      known X-linked disorders inherited in this fashion, Aicardi syndrome patients
      have a normal (i.e., random) X-inactivation pattern. A number of possible
      explanations is proposed for this apparently contradictory evidence.

PMID- 9272174
TI  - alpha-Thalassemia in The Netherlands: a heterogeneous spectrum of both deletions
      and point mutations.
AB  - In this article we describe the molecular characterization of 104 independent
      alpha-thalassemia patients identified by hematological analysis and family
      studies. During the study, another six chromosomes were identified with
      rearrangements of the alpha-cluster or point mutations in the alpha 2-globin
      gene, not associated with alpha-thalassemia, in healthy relatives of the
      patients. The molecular defects were established by Southern blot analysis and,
      if no deletions could be identified, the alpha-globin genes were investigated by
      denaturing gradient gel electrophoresis and single strand conformation analysis
      for the presence of point mutations. Following this strategy, we were able to
      identify the molecular basis of 131 independent alpha-thalassemia chromosomes. In
      two individuals, the alpha-thalassemia determinant could not be demonstrated at
      the molecular level. We identified eight different deletion and five non-deletion
      alpha-thalassemias, three rearrangements in the alpha-cluster, two alpha-chain
      variants, and a silent mutation in the alpha 2-globin gene not associated with
      alpha-thalassemia. The large heterogeneity of alpha-thalassemia mutations seen in
      the Dutch population might be typical for northern European countries where,
      besides the more common mutations introduced by migration, a variety of sporadic
      mutations was also found in the autochthonous population. The screening strategy
      as described here, capable of identifying a wide spectrum of both deletions and
      point mutations, identified 98% of the alpha-thalassemia determinants present in
      133 chromosomes.

PMID- 9272175
TI  - Removal of repetitive sequences from FISH probes using PCR-assisted affinity
      chromatography.
AB  - The vast majority of probes used in fluorescence in situ hybridization (FISH)
      contain repetitive DNA. This DNA is usually competed out of a hybridization
      reaction by the addition of an unlabeled blocking agent, Cot-1 DNA. We have
      successfully removed repetitive DNA from two complex FISH probe sets: a
      degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR) single
      human chromosome library and genomic DNA. The procedure involved hybridizing in
      solution a DOP-PCR-amplifiable probe set with a 50-fold excess of biotin-labeled
      Cot-1 DNA, and capturing the Cot-1 DNA-containing hybrids using streptavidin
      magnetic particles, followed by purification and reamplification of the unbound
      fraction. Probes were checked for depletion of repeats by hybridization to
      chromosomes without Cot-1 DNA. Results showed hybridization patterns comparable
      to those achieved with untreated probes hybridized with Cot-1 DNA.

PMID- 9272176
TI  - Mapping of a novel SH3 domain protein and two proteins of unknown function to
      human chromosome 21.
AB  - Down syndrome, caused by trisomy of human chromosome 21 (HSA21), is the most
      common autosomal form of mental retardation. To understand the aetiology of the
      syndrome we need to identify the genes involved. We have utilised the information
      generated by the various EST sequencing projects to enrich the transcription map
      of chromosome 21. Here we report the mapping of SH3P17 to 21q22.1 and the
      localisation of two genes previously mapped to HSA21 by Nagase and colleagues,
      KIAA0136 and KIAA0179 to 21q22.2 and 21q22.3, respectively. SH3P17 has unknown
      function but contains four SH3 domains. KIAA0136 shows no homology to a yeast
      open reading frame. Further investigation of these three genes will add to our
      functional understanding of HSA21.

PMID- 9272177
TI  - Mapping of the gene encoding the B56 beta subunit of protein phosphatase 2A
      (PPP2R5B) to a 0.5-Mb region of chromosome 11q13 and its exclusion as a candidate
      gene for multiple endocrine neoplasia type 1 (MEN1).
AB  - The multiple endocrine neoplasia type 1 (MEN1) locus has been previously
      localised to 11q13 by combined tumour deletion mapping and recombination studies,
      and a 0.5-Mb region, flanked by PYGM and D11S449, has been defined. In the course
      of constructing a conting, we have identified the location of the gene encoding
      the B56 beta subunit of protein phosphatase 2A (PP2A), which is involved in cell
      signal transduction pathways and thus represents a candidate gene for MEN1. We
      have searched for mutations in the PP2A-B56 beta coding region, together with the
      5' and 3' untranslated regions in six MEN1 patients. DNA sequence abnormalities
      were not identified and thus the PP2A-B56 beta gene is excluded as the candidate
      gene for MEN1. However, our precise localisation of PP2A-B56 beta to this region
      of 11q13 may help in elucidating the basis for other disease genes mapping to
      this generich region.

PMID- 9272178
TI  - The plakophilin 1 (PKP1) and plakoglobin (JUP) genes map to human chromosomes 1q
      and 17, respectively.

PMID- 9272179
TI  - Gene dosage effect in one family with myoclonic epilepsy and ragged-red fibers
      (MERRF).
AB  - OBJECTIVES: We analyzed the percentage of mitochondrial DNA (mtDNA) heteroplasmy
      in blood samples of 13 individuals belonging to a three family generation of
      myoclonic epilepsy with ragged-red fibers (MERRF) and compared the 5 affected
      patients and the 8 unaffected relatives. MATERIAL AND METHODS: DNA was extracted
      from blood and muscle of the proband and from blood of 12 maternal relatives. A
      PCR restriction analysis method was used to detect the mutation. RESULTS: The
      proband had the complete MERRF phenotype. The phenotype in three other
      individuals in the maternal lineage was consistent with the MERRF syndrome. The
      remaining were asymptomatic. The np 8344 mutation was observed in muscle and
      blood of the proband, and in blood from every one of 12 maternal relatives,
      ranging from 44% to 83% of mutated genomes. Symptomatic individuals had higher
      levels (P < 0.001) of mutated mtDNA than asymptomatic maternal relatives.
      However, high proportions of mutant genomes (up to 63%) were found in
      asymptomatic relatives. CONCLUSIONS: Although there seems to be a gene dosage
      effect in MERRF, we found no absolute relationship between the relative
      proportion of mutant genomes in blood and clinical severity. Factors other than
      gene dosage in blood may account for the differences in clinical phenotype.

PMID- 9272180
TI  - ECG changes in epilepsy patients.
AB  - OBJECTIVES: To investigate the frequency of ECG abnormalities suggestive of
      myocardial ischaemia in patients with severe drug resistant epilepsy and without
      any indication of previous cardiac disease, assuming that these changes may be of
      significance for the group of epileptic patients with sudden unexpected death.
      MATERIAL AND METHODS: Twelve patients with medically intractable epilepsy were
      investigated with simultaneous long ECG and EEG recordings while attending either
      epilepsy surgery investigational procedures or the investigational programme for
      diagnostic purposes, and one while having an episode of status epilepticus.
      RESULTS: The ECG recording failed in 1 patient. This patient had chest pain and
      minor yet morphologically conspicuous changes in the ECG, suggestive of
      myocardial infarction. He died in heart arrest. Eight epilepsy patients had
      episodes of ST segment depression in the ECG, many of which coincided with video-
      and EEG documented epileptic seizures. Two patients experiencing simple partial
      seizures and 1 patient experiencing absence seizures had no ST segment
      depressions in the ECG. One patient had an episode of status epilepticus
      secondary to brain damage and no ST segment deviation was seen during the ECG
      recording which continued until 3 h before the patient died. CONCLUSION: Patients
      with severe drug resistant epilepsy have episodes of ST segment changes, some of
      which are closely related to epileptic seizures. Further studies are needed to
      confirm the present results and to investigate the nature of these changes and
      document the effect of prophylactic treatment with cardioactive drugs to reduce
      the risk of sudden death.

PMID- 9272181
TI  - Validation of diagnostic criteria for solitary cerebral cysticercus granuloma in
      patients presenting with seizures.
AB  - OBJECTIVE: To evaluate a set of clinical and computed tomographic (CT) criteria
      (previously described by us) to predict the diagnosis of a solitary cerebral
      cysticercus granuloma (SCCG) at initial presentation, in patients presenting with
      seizures. MATERIAL AND METHODS: The diagnostic criteria were applied
      prospectively to patients presenting with seizures and solitary lesion on the CT
      scan. The clinical diagnostic criteria were as follows: seizures should be the
      presenting complaint; there should be no evidence of persistent raised
      intracranial pressure, progressive neurological deficit or an active systemic
      disease. The CT diagnostic criteria were: evidence of a solitary contrast
      enhancing lesion measuring 20 mm or less in its maximal dimension without a shift
      of the midline structures due to the surrounding oedema. A diagnosis of SCCG was
      made only when all the clinical and CT criteria were fulfilled. Over a period of
      36 months, we managed 401 patients presenting with seizures and a solitary mass
      on the CT scan; 215 met the criteria for the diagnosis of an SCCG. RESULTS: Of
      the 215 patients initially diagnosed to have an SCCG, 197 were ultimately
      determined to have that diagnosis (true positive diagnosis) while 16 were
      excluded because of lack of follow-up CT assessment. Two of the 215 patients with
      the initial diagnosis of an SCCG subsequently had histological diagnosis of a
      secondary metastasis and a pyogenic abscess (false positive diagnosis). Our set
      of diagnostic criteria for SCCG had a sensitivity of 99.5%; specificity of 98.9%;
      a positive predictive value of 99%; and a negative predictive value of 99.5%. The
      likelihood ratios for the positive and negative tests were 92.99 and 0.005
      respectively. CONCLUSIONS: Our diagnostic criteria help in not only accurately
      identifying an SCCG but also in differentiating it from a solitary tuberculoma
      and other brain masses. However, confirmation of the diagnosis of an SCCG is only
      obtained at follow-up evaluation and therefore careful clinical and CT re
      evaluation is essential in all patients initially diagnosed to have an SCCG.

PMID- 9272182
TI  - Prevalence of very mild to severe dementia in Denmark.
AB  - OBJECTIVES: The prevalence of dementia has been estimated in several countries
      and a meta-analysis has shown moderate and severe dementia in people aged 65
      years and older to be between 4% and 6%. The Odense study is aiming to estimate
      the prevalence and incidence of dementia and to identify risk factors. MATERIAL
      AND METHODS: A total of 3346 persons, equivalent to 64.5% of a random sample of
      5237 persons aged 65-84 years living in the municipality of Odense, Denmark,
      underwent a two phase diagnostic procedure including a screening with CAMCOG, the
      cognitive section of The Cambridge Examination for Mental Disorders of the
      Elderly, seven neuropsychological tests, medical examination, and CT scan. The
      severity of dementia was assessed by the CDR (Clinical Dementia Rating). RESULTS:
      The prevalence rate was 7.1%, including the very mildly demented, defined as
      persons rated questionably demented according to the CDR scale. The prevalence
      rate of very mild dementia was 2.8%. The proportion of cases with very mild
      dementia decreased with increasing age while the prevalence rate increased.
      CONCLUSION: Inclusion of very mild cases of dementia resulted in a higher
      prevalence rate than generally reported, and the prevalence rate increased
      exponentially with age which was mainly due to Alzheimer's disease.

PMID- 9272183
TI  - Ascorbate in healthy subjects, amyotrophic lateral sclerosis and Alzheimer's
      disease.
AB  - The aim of the present study was to report the levels of ascorbic acid in
      amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) and the
      effectiveness of ascorbic acid homeostasis in the central nervous system. Plasma
      and CSF ascorbic acid levels were measured by high performance liquid
      chromatography in 19 ALS patients, 17 AD patients and 15 controls. No
      statistically significant difference was found between patients and controls.
      However, wide fluctuations of plasma concentrations were found to result in
      relatively stable CSF levels, by appropriate adjustments of CSF/plasma ratio. It
      appears that in normal subjects and in the disease under study, this ratio
      reflects the activity of the choroid plexus ascorbate transporter.

PMID- 9272184
TI  - Nigro-striatal degeneration demonstrated in parkinsonian patients with iodine-123
      beta-CIT SPECT: methods of quantitation.
AB  - Single photon emission computed tomography (SPECT) images were obtained in 3
      healthy volunteers and 7 parkinsonian patients 22 h after injection of 120 MBq
      iodine-123-beta-CIT. There was a high radioactivity in the striatal region
      against a uniform background in the volunteers but pronouncedly reduced striatal
      activity in the patients. Total striatal activity in each hemisphere of each
      individual was calculated as the sum of all activity in excess of the background
      in all reconstructed images. There was a high correlation between reduction of
      striatal activity and motor scores in the unified rating scale for parkinsonism
      (URSP) for the patients. A method developed for calculation of the activity
      distribution along the length axis of the striatum indicated a more pronounced
      degeneration in the putamen compared with the caudate nucleus in the patients.
      Iodine-123-beta-CIT SPECT appears to be a good quantitative method for nigro
      striatal degeneration in parkinsonian patients.

PMID- 9272185
TI  - Intrathecal production of measles-specific IgA in subacute sclerosing
      panencephalitis.
AB  - OBJECTIVE: We measured measles-specific IgA in matched pairs of cerebrospinal
      fluid (CSF) and sera of patients with subacute sclerosing panencephalitis (SSPE),
      multiple sclerosis (MS), other central nervous system (CNS) infectious diseases
      (INF) and other neurological diseases (OND) by using enzyme linked immunosorbent
      assay. MATERIALS AND METHODS: CSF and sera from 23 patients with SSPE, 15 with
      MS, 14 with INF, and 15 with OND were included in the study. RESULTS: The ratios
      of measles-specific IgA in CSF to serum were increased in SSPE patients compared
      to patients with MS, INF or OND. CONCLUSION: The data indicate a local production
      of measles-specific IgA in the CNS of SSPE patients.

PMID- 9272186
TI  - Biologically active TGF-beta 1 is increased in cerebrospinal fluid while it is
      reduced in serum in multiple sclerosis patients.
AB  - OBJECTIVES: The polypeptide transforming growth factor-beta 1 (TGF-beta 1) is a
      product of activated monocytes, among other inflammatory cells, and it affects
      immune responsiveness, cellular growth and differentiation. TGF-beta 1 has potent
      T-cell inhibiting activities. It may play an important role in limiting
      autoimmune inflammation. We were interested about levels of biologically active
      and total TGF-beta 1 in serum and CSF in patients suffering from multiple
      sclerosis. SUBJECTS AND METHODS: We measured biologically active and total TGF
      beta 1 in serum and CSF using ELISA-technique in 64 MS patients with 57 during
      acute exacerbation of MS and 7 in remission (primary-relapsing: n = 59; primary
      progressive: n = 5), 20 healthy subjects, and 21 patients with other non
      inflammatory neurological diseases (OND). RESULTS: Biologically active TGF-beta 1
      in serum was reduced in MS patients compared to controls, on the other hand total
      TGF-beta 1 was elevated in CSF compared to patients with OND. Biologically active
      TGF-beta 1 in CSF correlated positively with the duration of the acute relapse in
      patients with primary-relapsing MS. The more relapses the patients had the higher
      was biologically active TGF-beta 1 in CSF. Total TGF-beta 1 in CSF correlated
      with macrophages in CSF and albumin quotient. CONCLUSION: We found that an
      elevated level of biologically active TGF-beta 1 in CSF might be useful as an
      indicator of disease limitation while active TGF-beta 1 in serum is reduced in
      multiple sclerosis. Measuring TGF-beta 1 in body fluids by ELISA techniques
      produces valid results and might be used for further studies focusing on the role
      of this cytokine in MS.

PMID- 9272188
TI  - Anterior horn cells are also involved in Japanese encephalitis.
AB  - INTRODUCTION: The basis of focal muscle wasting in Japanese encephalitis (JE) has
      not been systemically studied. MATERIAL AND METHODS: Twelve patients with JE were
      subjected to clinical evaluation, nerve conduction, electromyography (EMG), motor
      and somatosensory evoked potentials and cranial CT or MRI scans. Spinal MRI was
      carried out in selected patients. The clinical and the neurophysiological
      examination were repeated after 3 months. Recovery was defined as poor, partial
      and complete. RESULTS: Seven of 12 patients with JE had varying degrees of lower
      motor neuron signs. Electromyography revealed prominent fibrillation and
      neurogenic changes in the wasted muscles, which improved in the follow-up period
      in all patients. Motor evoked potentials on spinal stimulation revealed
      peripheral delay in 2 patients and small amplitude in 4 patients. Spinal MRI
      showed hyperintense signals on T2 in the cervical region which correlated with
      clinical signs. Two of these patients had complete, 3 partial and 2 poor
      recovery. The patients with mild involvement of spinal cord had better recovery
      compared to those with severe involvement. CONCLUSION: Varying degree of anterior
      horn cell involvement seems to be common in JE.

PMID- 9272187
TI  - Experimental bystander encephalitis induced by immunization with HTLV-I-producing
      T cells in mice.
AB  - ICR mice were immunized with HTLV-I carrier T lymphocytes (MT-2 cell line) and
      then inoculated intracerebrally with these cells. After non-specific traumatic
      hemorrhage, perivascular cell infiltration was noted diffusely throughout the
      brain on day 2 and lasted for over 2 weeks. HTLV-I antigens were detected in both
      sides of the cerebral hemisphere by Western blotting analysis. Tissue damage
      consisting of demyelination, axonal degeneration, and astrogliosis was observed
      most heavily on days 10 and 14. Non-immunized mice inoculated with the cells
      showed only transient hemorrhage. In cases using the HTLV-I free T-cell line
      (MOLT-4) inflammatory cell infiltration and tissue damage was much less
      conspicuous and disappeared after day 10. These experiments support the
      hypothesis that HAM/TSP is a bystander disease initiated and progresses via HTLV
      I-infected T-cell invasion into the spinal cord of a patient who has been
      infected and sensitized to the virus.

PMID- 9272189
TI  - An abnormal relationship between blood pressure and pulse rate in amyotrophic
      lateral sclerosis.
AB  - OBJECTIVES: To clarify the autonomic dysfunctions in amyotrophic lateral
      sclerosis (ALS) patients, we investigated the relationship between blood pressure
      (BP) and pulse rate (PR), QTc interval, and coefficient of variation in the R-R
      interval (CVR-R) in ALS patients. MATERIALS AND METHODS: BP and PR were
      determined automatically every 30 min for 24 h in 6 patients with ALS and in 18
      healthy age-matched volunteers. The QTc interval and CVR-R were also evaluated
      using an electrocardiogram. RESULTS: The relationship between BP and PR was lost
      in the ALS group. There was no significant difference in the QTc interval or CVR
      R between the ALS and control groups. CONCLUSION: We speculate that the imbalance
      between BP and PR observed in the ALS group reflects a disorder in the balance
      between the sympathetic and parasympathetic nervous systems.

PMID- 9272190
TI  - Increased leukocyte adhesiveness/aggregation in patients with recurrent TIA.
AB  - OBJECTIVE: White blood cells might have a pathogenetic role in ischemic vascular
      conditions. Several studies have suggested that increased adhesiveness of these
      cells could contribute to such a damage. The present study was undertaken in
      order to examine the adhesive properties of leukocytes in the peripheral blood of
      patients with various degrees of ischemic neuro-vascular diseases. METHODS: The
      percentage of aggregated white blood cells was determined by using a direct slide
      test. RESULTS: The respective values of aggregated cells in 28 patients with
      major stroke, 11 with minor stroke, 17 with a single TIA, 11 with recurrent TIAs
      and 18 controls were 15.9 +/- 7.4%, 6.6 +/- 3.3%, 3.0 +/- 2.6%, 10.9 +/- 8.4% and
      1.5 +/- 0.4%. The difference between patients with a single TIA and those with
      recurrent TIAs being significant at P < 0.05. CONCLUSION: Being a sensitive
      marker of inflammation, our test might reveal the presence of an underlying
      smoldering inflammation in patients with recurrent TIA. These results are in
      agreement with modern studies that show that inflammation is an important feature
      of atherosclerosis.

PMID- 9272191
TI  - High prevalence of benzodiazepine dependence in out-patient users, based on the
      DSM-III-R and ICD-10 criteria.
AB  - Despite the fact that there have been many reports on benzodiazepine (BZD)
      dependence, consensus about its definition has not been reached. Reliable
      prevalence data to estimate the dependence liability of BZDs are therefore
      lacking. This study is the first to assess the prevalence of BZD dependence in
      out-patient BZD users (115-general practice (GP) patients, 124 psychiatric out
      patients and 33 self-help patients) on the basis of the DSM-III-R and ICD-10
      substance dependence criteria. Past year and lifetime diagnoses of BZD dependence
      were made by means of the Schedules for Clinical Assessments in Neuropsychiatry
      (SCAN). High prevalence figures were found, ranging from 40% in the GP patients
      (DSM-III-R past year) to 97% in the self-help patients (ICD-10 lifetime),
      indicating that BZD users run a high risk of developing BZD dependence. The
      clinical management of BZD use could benefit from further development of
      diagnostic instruments such as a self-report questionnaire which reflects the
      severity of BZD dependence.

PMID- 9272192
TI  - The utilization of antidepressants--a key issue in the prevention of suicide: an
      analysis of 5281 suicides in Sweden during the period 1992-1994.
AB  - Antidepressants detected by the National Department of Forensic Chemistry in 5281
      suicides in Sweden during the period 1992-1994 were related to data on usage
      expressed in person-years of exposure. Antidepressants were detected in 874
      subjects (16.5%). In relation to their use, fluvoxamine, citalopram, moclobemide,
      mianserin and trimipramine were found more often than the reference drug,
      amitriptyline (i.e. over-risks). Toxic concentrations of antidepressants were
      detected in 232 subjects (4.4%). Most people committing suicide were not taking
      antidepressants immediately before their death, even though 40-85% may have been
      depressed. Undertreatment and therapeutic failure are the main problems with
      antidepressants, not the risk of using antidepressants in overdose. Comparisons
      of new antidepressants should focus on efficacy in relation to reference
      tricyclics. The huge increase in the use of antidepressants in Sweden since 1990
      1991 has been paralleled by a significant decrease in suicide rates.

PMID- 9272193
TI  - Eating disorders and antecedent anxiety disorders: a controlled study.
AB  - We compared the prevalence and age of onset of adult and childhood anxiety
      disorders relative to the primary diagnosis in 68 women with anorexia nervosa
      (AN), 116 women with bulimia nervosa (BN), 56 women with major depression with no
      eating disorder (MD) and 98 randomly selected controls (RC) in order to determine
      whether antecedent anxiety disorders are plausible risk factors for AN and BN.
      Comorbid anxiety disorders were common in all three clinical groups (AN, 60%; BN,
      57%; MD, 48%). In 90% of AN women, 94% of BN women and 71% of MD women, anxiety
      disorders preceded the current primary condition (P = 0.01), although panic
      disorder tended to develop after the onset of AN, BN or MD. In multivariate
      logistic regressions, the odds ratios (ORs) for overanxious disorder (OR = 13.4)
      and obsessive-compulsive disorder (OR = 11.8) were significantly elevated for AN.
      The ORs for overanxious disorder and social phobia were significantly elevated
      for BN (OROAD = 4.9; ORSP = 15.5) and MD (OROAD = 6.1; ORSP = 6.4). These data
      suggest that certain anxiety disorders are non-specific risk factors for later
      affective and eating disorders, and others may represent more specific antecedent
      risk factors.

PMID- 9272195
TI  - Spectral properties of phototherapy for seasonal affective disorder: a meta
      analysis.
AB  - The general therapeutic effect of light on seasonal affective disorder (SAD) has
      been widely acknowledged. However, the antidepressant effect of light does not
      seem to be the same for different spectra of light. In this study, the authors
      attempted to study the spectral properties of phototherapy for SAD using a meta
      analytical procedure. The findings suggested that light of short to medium
      wavelengths (blue/green/yellow) seem to be essential for the therapeutic effect
      of light on SAD. Red wavelengths were relatively ineffective. It was then
      postulated that SAD may be predisposed and/or precipitated by the inefficiency of
      the S and M cones in the retina. Furthermore, ultraviolet (UV) waves did not seem
      to be essential for SAD symptom alleviation by artificial light. Therefore, these
      potentially harmful UV waves should be blocked in any clinical application of
      phototherapy for SAD.

PMID- 9272194
TI  - A cross-cultural breakdown of Swedish suicide.
AB  - In this cross-cultural, nation-wide study including all immigrant groups in
      Sweden, over 10,000 suicides and undetermined cases occurring during the period
      1987-1991 were analysed. Diagnoses of the underlying causes of death were
      classified according to ICD-9, all of the alternatives E950-E959 and E980-E989
      being selected. Definite and overall suicide rates were estimated for each
      immigrant group represented. We found an overrepresentation of immigrants in the
      Swedish suicide statistics nation-wide. A total of 15 countries (60% of the
      immigrant population) manifested more observed than expected suicides and
      undetermined cases. This overrepresentation was statistically significant among
      immigrants from Russia, Finland, Germany, Denmark and Norway (the immigrant
      population of these countries represents nearly 50% of the total population of
      immigrants in Sweden). Other nationalities with an increased suicide incidence
      were from Poland, Hungary, Czechoslovakia, Austria, Korea, The Netherlands,
      France, Spain and Uruguay. The risk of an immigrant dying of a cause related to
      suicide was found to be 1.5 times higher than that for a native Swede.
      Furthermore, the increased suicide rates observed among the immigrant groups in
      Sweden were found to be higher than in the respective countries of origin for 90%
      of the nationalities investigated, including those characterized by a relatively
      high refugee flow to Sweden, the rank order being generally the same both in the
      countries of origin and in Sweden. The immigrant groups with the highest suicide
      rates in our study were from Russia, Finland and Hungary. Suggestions are made
      concerning the possible involvement of underlying cultural, anthropological and
      genetic factors in this phenomenon.

PMID- 9272196
TI  - Depression in Finland: a computer assisted telephone interview study.
AB  - We examined the prevalence of depressive disorders and associated factors in the
      general population in Finland using the Computer-Assisted Telephone Interview
      (CATI) method. A total of 2293 (71%) of 3250 individuals randomly drawn from the
      population registry and representing the adult population of Finland in the age
      group 25-79 years were interviewed by telephone in autumn 1994. The interview
      included a short form of the University of Michigan version of the Composite
      International Diagnostic Interview (UM-CIDI) generating probability diagnoses of
      DSM-III-R major depressive episode and dysthymia. The age-adjusted 6-month
      prevalence was 4.1% for major depressive episode and 1.7% for current dysthymia;
      depressive mood during the preceding month was reported in 17% of cases. Major
      depressive episodes and depressive mood were significantly more prevalent among
      females than males. In the logistic regression analyses, factors associated with
      the depressive disorders were found to vary somewhat depending on sex and type of
      disorder. Only about 50% of those with major depressive episode or dysthymia
      reported a self-perceived need for mental health services.

PMID- 9272197
TI  - Therapeutic options in Charles Bonnet syndrome.
AB  - The term 'Charles Bonnet syndrome' refers to visual pseudohallucinations
      occurring especially in elderly people with reduced visual acuity. Despite
      numerous case reports, few successful methods of treatment have been described.
      Therapies with classical neuroleptics, antidepressants or benzodiazepines have
      generally been found to be unpromising. Only with carbamazepine treatment has
      improvement been observed in a few cases. In the three cases reported here, we
      successfully treated the condition with the atypical neuroleptic melperone.

PMID- 9272198
TI  - Double-blind randomized controlled study of the efficacy and tolerability of two
      reversible monoamine oxidase A inhibitors, pirlindole and moclobemide, in the
      treatment of depression.
AB  - The aim of this double-blind randomized study was to compare the efficacy and the
      tolerability of moclobemide (300-600 mg daily) and pirlindole (150-300 mg daily),
      two reversible inhibitors of MAO-A (RIMAs), in the treatment of depression. In
      total 116 patients were included in the trial, 111 patients (52 patients on
      pirlindole and 59 patients on moclobemide) were evaluable for efficacy and
      safety, and 77 patients completed the whole study (42 days of administration).
      Both treatments produced highly significant improvements in the Hamilton
      Depression Rating Scale (HDRS) score, the Hamilton Anxiety Rating Scale (HARS)
      score and the Montgomery-Asberg Rating Scale (MADRS) score from day 7 to day 42.
      The pattern of development of the three scores in the two groups did not differ
      significantly. After 42 days of treatment, an improvement of > or = 50% in the
      HDRS score was noted in 80% and 67% of patients in the pirlindole and moclobemide
      groups, respectively. A total of 30 (58%) patients on pirlindole and 33 (56%)
      patients on moclobemide experienced side-effects that were considered to be
      possibly or probably related to the medication. The differences between the two
      drugs were non-significant for all types of side-effect, with the exception of
      dry mouth and tachycardia, which were significantly more frequent with
      moclobemide.

PMID- 9272199
TI  - Hopelessness, impulsiveness and intent among suicide attempters with major
      depression, alcohol dependence, or both.
AB  - The present study examined differences in hopelessness, impulsiveness and suicide
      intent between suicide attempters with either major depression or alcohol
      dependence, comorbid major depression and alcohol dependence, and those without
      these disorders. A sample of 114 patients from consecutive cases of attempted
      suicide referred to a general hospital in Helsinki was interviewed and diagnosed
      according to DSM-III-R. Suicide intent was measured by the Beck Suicide Intent
      Scale (SIS) and hopelessness was assessed by the Beck Hopelessness Scale (HS).
      Impulsiveness of the suicide attempt was measured by two items of the SIS.
      Suicide attempters with major depression without comorbid alcohol dependence had
      higher suicide intent and lower impulsiveness than attempters with non-depressive
      alcohol dependence. Suicide attempts may differ between subjects with major
      depression, alcoholism or both disorders in terms of impulsiveness and suicide
      intent.

PMID- 9272200
TI  - Acute and transient psychotic disorder: a 1-year follow-up study.
AB  - A study sample consisting of 51 patients suffering from acute and transient
      psychotic disorder (ATPD) (ICD-10) on initial examination was evaluated at 1-year
      follow-up. The findings show a diagnostic change in half of the patients (48%),
      most often to schizophrenia (15%) and affective disorder (28%). From index
      admission to follow-up, patients with an unchanged diagnosis of ATPD manage
      fairly well with regard to psychosocial functioning, and no deteriorating
      development is observed. In the majority of cases no personality disorder (PD)
      (ICD-10, 54%; DSM-IV, 71%) is apparent, and the ATPD is not related to any
      specific PD. With regard to diagnostic stability, no significant demographic,
      social or clinical predictors were found. The findings highlight the need for
      validation of the concept of ATPD, and point to the fact that brief psychotic
      episodes with an acute onset may be an early manifestation of severe mental
      disorder (schizophrenia and affective disorder).

PMID- 9272201
TI  - Thyroid hormone and reserpine abolished periods of periodic catatonia: a case
      report.
AB  - We report the case of a patient whose periods of periodic catatonia were
      abolished by thyroid hormone and reserpine. A ratio of fractions in the urinary
      17-ketosteroids was a good indicator for the treatments.

PMID- 9272202
TI  - Current clinical options for diagnosis and treatment of recurrent spontaneous
      abortion. Clinical Guidelines Recommendation Committee for Diagnosis and
      Treatment of Recurrent Spontaneous Abortion.

PMID- 9272203
TI  - HLA-G finally does something!

PMID- 9272204
TI  - Presence of HLA-G-expressing cells modulates the ability of peripheral blood
      mononuclear cells to release cytokines.
AB  - PROBLEM: Human leukocyte antigen-G (HLA-G) is thought to be at play in maternal
      fetal immune interplay during pregnancy. Whether the expression of HLA-G protein
      on the target cells altered the release of cytokines from effector mononuclear
      cells was questioned. METHOD OF STUDY: The amounts of cytokines released from
      peripheral blood mononuclear cells (PBMC) cocultured with or without HLA-G
      expressing target cells were compared. RESULTS: When cocultured with HLA-G
      expressing target cell lines, the amounts of interleukin-3 (IL-3) and interleukin
      1 beta (IL-1 beta) released from PBMC were increased, whereas the amounts of
      tumor necrosis factor-alpha (TNF-alpha) were decreased. CONCLUSIONS: Mononuclear
      cells, if cultured with HLA-G-expressing cells, modulate their ability to release
      cytokines, suggesting a role of HLA-G in triggering maternal-fetal immune
      interplay and thereby maintaining pregnancy.

PMID- 9272205
TI  - Pathogenetic implication of interleukin-2 expressed in preeclamptic decidual
      tissues: a possible mechanism of deranged vasculature of the placenta associated
      with preeclampsia.
AB  - PROBLEM: The purpose of this study is to clarify whether IL-2 expressed in the
      decidua in preeclampsia affects the angiogenesis of the placenta. METHOD OF
      STUDY: We investigated the angiogenic substances released from human trophoblasts
      obtained from early pregnancy that had been pretreated with either IL-2, non
      activated lymphocytes from peripheral blood mononuclear cells (PBMCs), decidual
      lymphocytes, or these lymphocytes activated by lymphokine (LAK cells). Angiogenic
      activity was determined by evaluating the ability of growth-promotion of cultured
      human microvascular endothelial cells (HMvECs) using MTT assay. RESULTS:
      Trophoblasts pretreated with IL-2 or non-activated lymphocytes, irrespective of
      their origin, released angiogenic factor similar to those without pretreatment.
      However, trophoblasts pretreated with LAK cells released less angiogenic factor
      compared with those without pretreatment. CONCLUSIONS: Interleukin-2 (IL-2)
      expressed in preeclamptic decidua might reduce the angiogenic substances arising
      from trophoblasts by inducing LAK-cells from decidual lymphocytes, which might be
      relevant to deranged vasculature of the placenta, a characteristic histology in
      preeclampsia.

PMID- 9272206
TI  - Evidence for an elevation in serum interleukin-2 and tumor necrosis factor-alpha
      levels before the clinical manifestations of preeclampsia.
AB  - PROBLEM: The purpose of this study is to clarify whether the disruption of immune
      regulation occurs in early pregnancy before the clinical manifestations of
      preeclampsia. METHOD OF STUDY: The serum concentrations of interleukin-2 (IL-2)
      and tumor necrosis factor-alpha (TNF-alpha) were determined by using enzyme
      linked immunoadsorbent assay (ELISA) in the first trimester of pregnancy in women
      who had preeclampsia develop after 28 weeks of pregnancy (preeclamptic group) and
      in women who completed pregnancy uneventfully (control group). RESULTS: Serum
      concentrations of both IL-2 and TNF-alpha in the first trimester of the
      preeclamptic group were significantly higher than those of the control group.
      CONCLUSIONS: That the perturbation of feto-maternal immune regulation may precede
      the clinical manifestations of preeclampsia, which may be of relevance in the
      development of preeclampsia, is suggested.

PMID- 9272207
TI  - T-helper 2 type cytokine and soluble interleukin-2 receptor levels in seminal
      plasma of infertile men.
AB  - PROBLEM: The role of cell-mediated immunity (CMI) in unexplained male infertility
      and impaired sperm function has been explored. METHOD OF STUDY: The presence of
      cytokines, namely, interleukin-4 (IL-4), interleukin-6 (IL-6), and the soluble
      interleukin-2 receptor (SIL-2R), was investigated in seminal plasma of 18 fertile
      and 20 infertile subjects, using specific enzyme-linked immunoadsorbent assays.
      RESULTS: IL-4 was not detected. SIL-2R was detected, but the concentration
      difference between the fertile and infertile group was not significant. IL-6 was
      detected with significantly higher levels in the infertile group compared to the
      fertile group. IL-6 levels in seminal plasma correlated positively with leukocyte
      count and negatively with sperm count, motility, and morphology. CONCLUSIONS:
      These findings show: a) a lack of IL-4 in seminal plasma; b) similar SIL-2R
      levels in fertile and infertile seminal plasma; c) increased IL-6 secretion in
      seminal plasma of infertile subjects; and d) specific correlations of IL-6 with
      the main semen parameters.

PMID- 9272208
TI  - Anti-endometrial autoantibodies in women with a diagnosis of infertility.
AB  - PROBLEM: The purpose of this study was to investigate the frequency of anti
      endometrial antibodies (AEA) in infertile women. METHOD OF STUDY: Sera from
      fertile women (n = 6), and from patients with ovulatory dysfunction (n = 11),
      tubal obstruction (n = 9) and unexplained infertility (n = 5) were investigated
      for the presence of anti-endometrial membrane antibodies. We used two human
      endometrial cancer cell lines and human endometrial cells from gynecological
      biopsies as an antigenic source for analysis. The immunoenzymatic assay (ELISA)
      was performed with cultured endometrial cells in monolayers. Immunoblot analysis
      was performed with these two cell lines. RESULTS: A good correlation between the
      response with each cell line and with human endometrial cells was obtained,
      indicating that the antigens analyzed were probably similar. Endometrial
      antibodies were detectable in a high percentage of women with tubal obstruction
      (77.8 and 66.7%, respectively) and ovulatory dysfunction (54.5 and 45.5%,
      respectively). Unexplained infertility showed anti-endometrial immunological
      response (40 and 60%, respectively). Some endometrial antigens in infertile women
      are the target for autoimmune response. The serum from a patient with tubal
      obstruction and ovulatory dysfunction showed two antigens by immunoblot, with
      molecular weights of 97 and 50 kDa. CONCLUSION: The presence of anti-endometrial
      antibodies, detected by ELISA, is associated with infertility, mainly with
      ovulatory dysfunction and tubal obstruction. Some endometrial antigens may be
      involved in these two pathologies.

PMID- 9272209
TI  - Effect of boar seminal immunosuppressive component on humoral immune response in
      mice.
AB  - PROBLEM: The effect of seminal immunosuppressive component (ISF) on the primary
      and secondary antibody response, induced by soluble and/or corpuscular antigens,
      was evaluated in the sera obtained at different intervals before and after
      immunizations. The duration of the immune suppression induced by ISF treatment
      within the primary and secondary immunizations was also determined. METHOD OF
      STUDY: The ability of the seminal immunosuppressive component to suppress the
      primary and secondary antibody response was evaluated by enzyme-linked
      immunoadsorbent assay (ELISA) in the sera of mice treated in vivo with the
      immunosuppressor before and after immunization with antigens. Likewise, the
      duration of the immune suppression induced by the seminal immunosuppressor
      administered before the primary and secondary immunizations was tested by ELISA
      with antisera to keyhole limpets hemocyanin. RESULTS: Intravenous and rectal
      deposition of ISF led to a suppression of the primary and secondary antibody
      response to soluble and corpuscular antigens. The most effective suppression of
      the immune response was achieved in mice treated with immunosuppressor 3 days
      before the immunization with antigens. Also the secondary antibody response to
      the challenging antigen was significantly suppressed by ISF. The production of
      immunoglobulin G (IgG), IgM, and IgA to keyhole limpets hemocyanin was depressed
      for a relatively long period in mice treated with the immunosuppressor. The
      results indicated that the preexposure is needed for maximal immunosuppression of
      the primary antibody production. The treatment with ISF led to a prolonged
      immunosuppression but not to permanent tolerance to the challenging antigen.
      CONCLUSIONS: The in vivo deposition of semen may compromise some aspects of the
      immune system and may be an important factor in the development of viral and
      bacterial infections. The suppression of humoral immune response suggests
      potential uses of seminal immunosuppressor for the animal model study in the
      therapy of antibody-mediated diseases.

PMID- 9272210
TI  - The anovulation in female mice resulting from postnatal injections of estrogen is
      correlated with altered levels of CD8+ lymphocytes.
AB  - PROBLEM: Injections of estradiol-17 beta (E2) are known to both induce
      anovulation and alter lymphocyte maturation in female mice. The current study
      examined whether the two events are related. METHOD OF STUDY: Female (C3H/HeJ x
      129J)F1 (C31) mice were injected with 20 micrograms of E2 from 0-3 days, or from
      3-6 days, postpartum. At 8, 12, 20, 32, or 40 weeks of age, the animals were
      killed, T lymphocytes were characterized, and ovaries were histologically
      examined for the presence of corpora lutea. RESULTS: Animals injected with E2
      from 0-3 days postpartum had percentages of CD8+ thymocytes and CD8+ splenocytes
      that were always lower than in noninjected females, and the E2-injected animals
      never ovulated, even by 40 weeks of age. In contrast, animals injected with E2
      from 3-6 days of age had percentages of CD8+ thymocytes and CD8+ splenocytes
      that, although initially lower than in control females, attained control values
      by 32 weeks of age. In addition, at 32 weeks of age a number of the 3-6-day E2
      injected females ovulated, whereas at earlier ages none had. Further, injections
      of E2 had little effect on the percentages of CD4+ thymocytes and splenocytes in
      these animals. CONCLUSIONS: The results suggest that E2-induced anovulation in
      C31 female mice is correlated with decreased levels of CD8+ lymphocytes, and an
      increased CD4+/CD8+ lymphocyte ratio.

PMID- 9272211
TI  - The regulatory role of transforming growth factor-beta in activation of milk
      mononuclear cells.
AB  - PROBLEM: Immunoregulatory role of milk mononuclear cells and cytokines during the
      involution of the mammary gland. METHOD OF STUDY: Bioassays were used to
      determine the levels of transforming growth factor beta (TGF-beta) and
      interleukin-2 (IL-2) and their effects on milk mononuclear cells (MMCs). RESULTS:
      MMCs collected from involuting glands were less responsive to Con A stimulation
      than peripheral blood mononuclear cells (PBMCs), and purified huTGF-beta 1
      inhibited the activation of both MMCs and PBMCs by Con A. Furthermore, secretions
      collected over a period of approximately 4 weeks into the involution period
      contained high levels of active TGF-beta and extremely high levels of latent TGF
      beta, MMCs stimulated with Con A produced higher levels of IL-2 than did the
      PBMCs of the same animals, and bovine milk TGF-beta and huTGF-beta 1
      significantly inhibited the IL-2 production by MMCs. Mammary secretions of
      involuting glands did not contain any detectable levels of IL-2, and they
      inhibited the growth of the IL-2-dependent bovine lymphoblastoid T cell line
      (BLTC), even in the presence of 10 U/ml of rBo IL-2. CONCLUSIONS: The findings
      suggest that TGF-beta is a major immunoregulatory factor in the involuting
      mammary gland.

PMID- 9272212
TI  - TGF-beta 2 and PGE2 in rabbit blastocoelic fluid can modulate GM-CSF production
      by human lymphocytes.
AB  - PROBLEM: During normal pregnancy, major changes occur in the production of
      Th2/Th1 cytokines at the feto-maternal interface. Th2 cytokines such as
      interleukin-4 (IL-4) or interleukin-10 (IL-10) are predominantly produced locally
      in the uterine and placental tissues, whereas the production of Th1 cytokines
      such as tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma)
      are decreased. Because these modulation might be induced by the embryo, the
      current study was carried out to test the effect of rabbit blastocoelic fluid on
      the production of Th2/Th1 cytokines by lymphocytes, and to investigate the
      possible implication of transforming growth factor beta 2 (TGF-beta 2)
      prostaglandin E2 (PGE2) as modulators of the production of these cytokines.
      METHOD OF STUDY: Human peripheral blood lymphocytes (PBL) were cultured along
      with ConcanavalinA(Con A), and rabbit blastocoelic fluid was collected on day 12
      of gestation (BF d-12). Concentrations of cytokines in culture media were
      determined by enzyme-linked immunoadsorbent assay (ELISA). RESULTS: Addition of
      BF d-12 in the culture medium induced a strong inhibition of IL-2, TNF-alpha, IL
      10, and granulocyte-macrophage colony-stimulating factor (GM-CSF) production.
      However, an initial pretreatment of the lymphocytes with BF d-12, followed by a
      Con A stimulation, led to a marked increase in GM-CSF production, whereas IL-2,
      TNF-alpha, and IL-10 secretions were inhibited. It was also demonstrated, for the
      first time, that a pretreatment of the lymphocytes with TGF-beta 2 and PGE2
      increased GM-CSF production to the same level reached after the addition of BF d
      12. Furthermore, removal of TGF-beta 2 and PGE2 from BF d-12 by affinity
      chromatography reduced the effect of BF d-12 on GM-CSF production. CONCLUSIONS:
      Taken together, these findings suggest that the embryo, in modulating harmful and
      beneficial cytokine production locally, plays an active role in its protection
      against maternal immune cellular assault. These results also emphasize the
      importance of growth factors for successfully maintaining pregnancy.

PMID- 9272213
TI  - Behavior of carbonate and magnesium ions in the initial crystallites at the early
      developmental stages of the rat calvaria.
AB  - Analysis of the contents of calcium (Ca), magnesium (Mg), phosphate, and
      carbonate ions in the mineral phase of rat calvaria specimens obtained at
      different developmental stages indicated that the mineral at the newborn stage
      contained a negligible amount of carbonate, but a high content of Mg. There was
      no significant difference in Ca and phosphate (as PO4) contents between the
      newborn material and that from later stages. A relatively large amount of
      carbonate was detected in the calvaria from 6-day-old rats, in which only
      immature crystals were observed, thus indicating the beginning of apatite
      formation. Furthermore, using laser Raman microprobe analysis we confirmed that
      the Raman peak at 1120 cm-1 band, indicative of a Mg-CO3 compound, appeared at
      the 6-day stage. We also observed that the Raman peak at 988 cm-1 found in the
      samples from the newborn seemed to have shifted to 963-962 cm-1 in the case of
      those obtained from 6-day-old rats, a shift which suggests the conversion from
      the non-apatitic to the apatitic form. These results indicate that carbonate ions
      might facilitate the initiation of crystal development by converting the
      inhibitory Mg ion into its inactive form (Mg-carbonate compound).

PMID- 9272214
TI  - Some remarks on, and a new case of the rare os intercuneiforme (Dwight).
AB  - A new case of the rare os intercuneiforme (Dwight) is presented and compared with
      the two cases reported by the anatomist first describing this bone. Taking a
      large series of anatomical investigations into account, the frequency of
      occurrence for this supernumerary tarsal bone can be given as 0.026%.
      Furthermore, it is supposed that the os intercuneiforme belongs rather to the
      medial than to the intermediate cuneiform.

PMID- 9272215
TI  - Functional role of V form distribution seen in microvascular cast specimens of
      the filiform and fungiform papillae on the posterior central dorsal surface of
      the cat tongue.
AB  - The relationship between the functional role and three-dimensional structures of
      the microvascular network of the filiform papillae (FiP) and fungiform papillae
      (FuP) on the posterior central surface of the cat tongue were observed by the
      corrosion cast method under a scanning electron microscope (SEM). FiP can be
      classified into five types; types I-V (Ojima and Lowe 1995), and FuP, found to be
      distributed sporadically among FiP (I-V), into four types; types I-IV (Ojima et
      al. 1996 b) according to the shape and size of the main process (MP) and the
      number of the accessory processes (AP). Each of the types I-V of FiP were
      arranged in the form of a V as oblique lines running in an orderly and
      geometrical fashion from the posterior central zone to the anterior peripheral
      zone in both directions. Each of the types I-IV of FuP were scattered throughout
      the line of FiPs arranged in the form of a V, the point of which is directed
      towards the pharynx. FiPs play an important role in the drinking of milk and
      water, holding, masticating and swallowing the food and, after mixing the food
      with saliva, in the transporting of the food mass towards the pharynx. The MP of
      FuPs is considered to be a modified form of the MP of FiP of the cat tongue
      function (Ojima et al. 1996 c) as part of a sense organ for taste.

PMID- 9272216
TI  - Angioarchitectural structure of the fungiform papillae on rabbit tongue
      anterodorsal surface.
AB  - The relationships between the functional and morphological characteristics and
      the positional difference of the microvascular cast specimen (MVCS) of the
      fungiform papillae (FuP) on the antero-dorsal surface of the rabbit tongue were
      examined and compared using a scanning electron microscope (SEM). The sporadic
      FuPs scattered among the numerous small filiform papillae (SfP) were found to be
      distributed irregularly over the antero-dorsal surface. FuPs consisted of the
      ascending and descending capillary loops, forming margins of the central opening
      at the top of FuP. They resembled flower-like configurations (carnations), the
      petals of which ranged from eight to twelve, and they were larger in width and
      more complex in shape than SfPs with morphological differences. FuPs can be
      classified into three types: type I (consisting of eight petals), type II (ten
      petals), type III (twelve petals) according to the shape of FuP, and to the petal
      number of the flower-like aspect on the eight points of MVCS of FuPs observed by
      SEM. These results suggest that the petals of the ascending and descending
      capillary loops of FuP expanded the flower-like figure, increased in the surface
      areas and effectively play a role in receiving the sense of taste.

PMID- 9272217
TI  - Sulcal pattern of the anterior parahippocampal gyrus in the human adult.
AB  - The sulcal pattern of the human entorhinal region, located in the anterior
      portion of the parahippocampal gyrus, was investigated in 184 brain hemispheres
      of both sexes between the ages of 19 and 85 years. A new classification of the
      sulcal pattern is introduced with reference to the extension of the collateral
      and rhinal sulci. Both sulci were found in all the investigated hemispheres. The
      collateral sulcus is a continuation of the rhinal sulcus in 41.9%. The rhinal
      sulcus represents the anterolateral border of the entorhinal region. By defining
      four branches of the rhinal sulcus all the possible ramifications occurring in
      the investigated hemispheres could be described. In 19.0% of the cases, a well
      developed entorhinal sulcus emerges in the central portions of the entorhinal
      region. An incipient entorhinal sulcus is evident in 29.6% and the sulcus is
      absent in 51.4% of the investigated cases. The intrarhinal nick, resulting from
      the impression of the free edge of the cerebellar tent, is seen as a dip in 35.1%
      and as a notch in 34.5%. It is absent in 30.4% of the cases. A comparison between
      the right and left hemispheres, as well as between the female and male sexes,
      revealed only minor differences of the sulcal pattern.

PMID- 9272218
TI  - Ultrastructure of ventral epidermis in the terrestrial and aquatic phases of the
      newt Triturus vittatus (Jenyns).
AB  - The ultrastructure of the ventral epidermis is described in the aquatic and
      terrestrial phases of the newt Triturus vittatus (Jenyns). In both phases, the
      stratum corneum is characterized by a large number of keratinocytes and bundles
      of tonofilaments. Mitochondria-rich flask cells were found in both phases. The
      main difference was found in the abundant tuberculi on the surface, and in the
      number of stratum corneum replacement layers found in the terrestrial phase. The
      epidermis of the aquatic phase did not show any resemblance to the aquatic larval
      stage, thus no Leydig cells could be found.

PMID- 9272219
TI  - Digestibility of phosphorus in protein-rich ingredients for pig diets.
AB  - Two experiments were run to determine the digestibility of phosphorus in
      different vegetable and animal proteins for the pig diet. Each experiment
      comprised two 4 x 4 Latin squares run concurrently. Pigs initially weighing 30 kg
      were kept in metabolism crates and fed twice daily at about 2.5-fold
      metabolisable energy requirement for maintenance. A semi-purified basal diet low
      in phosphorus and without intrinsic phytase activity was fed either alone or
      after blending into mixtures with one of the ingredients to be tested. Mixtures
      were calculated to contain not more than 2 g digestible P/kg DM and between 5.0
      and 6.0 g Ca/kg DM. Faeces and urine were quantitatively collected for 8 days
      after 7 days of adaptation. Phosphorus digestibility for ingredients under test
      was calculated assuming the digestibility of phosphorus from the basal diets to
      be constant in all diets. P digestibilities in solvent extracted soybean meal
      from dehulled seed, rapeseed and solvent extracted rapeseed meal were 37, 42 and
      24%, respectively. Supplementation of a microbial phytase (750 U/kg diet)
      improved digestibility coefficients significantly to 76, 66 and 73%,
      respectively. Digestibility of phosphorus in 3 different batches of fish meal
      ranged from 85 to 90%, without significant differences between batches. In 3
      different types of carcass meal, digestibility coefficients were 80, 82 and 83%
      without significant differences between types, and digestibility of phosphorus
      from bone meal was 80%.

PMID- 9272220
TI  - Formation and disappearance of mycophenolic acid, patulin, penicillic acid and PR
      toxin in maize silage inoculated with Penicillium roqueforti.
AB  - Maize silage was inoculated with Penicillium roqueforti strains which are able to
      form the mycotoxins mycophenolic acid (MPA), patulin (PAT), penicillic acid (PA),
      or PR toxin (PRT). The silage was incubated for 160 d without agitation under
      aerobic conditions at 15 degrees C in the dark. The mycotoxins were quantified by
      HPLC and identified by HPLC combined with diode array detection and by two
      dimensional thin layer chromatography. MPA, PAT, PA, and PRT above the detection
      limit were measured for the first time at 36, 22-27, 13, and 49 days of
      incubation, maximum toxin contents (mg/kg) were 3.56 MPA, 15.10 PAT, 3.06 PA, and
      2.17 PRT. With increasing storage time toxin contents decreased to a low or non
      detectable level. The production of MPA, PAT and PRT was preceded by an increase
      in pH from 4 to 8-9. Along with the initial pH increase the content of ergosterol
      as well as of P. roqueforti and yeast propagules increased whereas the levels of
      total soluble sugar and of water extractable NH3 decreased. It is concluded that
      the probability to detect MPA, PAT, PA, and PRT in maize silage moulded by P.
      roqueforti under practical conditions of agriculture is low during the growth of
      this fungus and again after prolonged storage.

PMID- 9272221
TI  - Retention and utilization of amino acids in piglets fed ad libitum or
      restrictively diets supplemented with organic acids.
AB  - In a metabolic trial 4 groups of 8 piglets of 5 kg weight each were kept
      individually for 45 days (final weight 23 kg) and fed a practical diet. At the
      beginning of the experiment the body amino acid contents of an additional group
      of 8 piglets were determined by carcass analysis, and at the end of the
      experiment the body amino acid contents of the 4 test group piglets (A = control
      fed ad libitum, B and C = supplement of 1.5% fumaric acid fed ad libitum or
      restrictively, D = supplement of 1.5% citric acid fed ad libitum) were also
      analysed. The amino acid retention during the experimental period was determined
      by difference. The supplements of fumaric or citric acid did not influence the
      amount of the amino acid retention. The quotient of amino acid retention to amino
      acid consumed or the "productive amino acid value" was calculated and the
      maintenance requirements of essential amino acids for piglets were used to
      estimate the productive amino acid value for both retention and maintenance. The
      mean amino acid retention amounted to about 56 g/d, i.e. 3.49 g/kg W0.75.d of
      essential amino acids. The essential amino acid requirements for maintenance was
      2.0 g, i.e. 0.29 g/kg W0.75.d, showing a variation of 4% (Leu) to 20% (Met+Cys)
      when related to the amount of the corresponding amino acid retention. With regard
      to the amino acid pattern for retention of the nutritionally most important amino
      acids, the following ratios were found: Lys, 100 (6.27 g/16 g N): Met+Cys, 48
      (3.03 g): Thr, 56 (3.49 g): Trp, 13 (0.80 g). The productive amino acid values
      ranged from 40% (Trp), 55% (Thr), 66% (Met) to 80% (Lys). Under the conditions
      investigated, neither the supplements of organic acids nor the feed restriction
      influenced the amino acid utilization.

PMID- 9272222
TI  - Influence of duodenal infusion of nicotinic acid on the milk fat composition of
      dairy cows.
AB  - Two experiments I and II, with 2 and 4 lactating dairy cows respectively, each
      fistulated with ruminal and duodenal cannulae, were carried out. The effects on
      milk composition and milk fat fatty acids' pattern through a continuous daily
      infusion into the duodenum with 6 g nicotinic acid were investigated. Treatments
      were nicotinic acid (NA) infusion in experiment I, and nicotinic acid infusion
      plus feeding 270 g of stearic acid in experiment II. No application of NA and
      stearic acid in experiments I and II respectively, acted as controls. Nicotinic
      acid infusion did not significantly influence protein, fat and lactose contents
      of milk. In both experiments, infusion of nicotinic acid decreased the proportion
      of short and middle chain fatty acids in milk fat and increased significantly the
      percentage of oleic acid from 19.0 to 25.4%. The addition of stearic acid alone
      had no effect on milk composition and fatty acids' pattern. Additional infusion
      of nicotinic acid infusion significantly increased nicotinamid concentration in
      the milk from 49.7 to 87.2 micrograms/100 ml.

PMID- 9272223
TI  - Influence of vitamin C, vitamin E and beta-carotene on the osmotic fragility and
      the primary antioxidant system of erythrocytes in zinc-deficient rats.
AB  - The present study was designed to investigate the effect of antioxidant
      supplementation on the in vitro osmotic fragility of erythrocytes from zinc
      deficient rats. Rats were fed either a zinc-adequate diet, zinc-deficient diet or
      a zinc-deficient diet enriched either with vitamin C or vitamin E or beta
      carotene. Components of the primary antioxidant system of erythrocytes,
      parameters of hemolysis in vivo and indicators of liver injuries were also
      examined. In order to ensure adequate and identical food intake rats were force
      fed by intragastric tube. The supplementation with antioxidants led to a marked
      improvement of the osmotic fragility without having influenced zinc status of the
      animals and components of the antioxidant system. The strongest effect was
      exerted by vitamin E. The rats fed the zinc-adequate diet (control group) showed
      unusually high values of erythrocytes osmotic fragility. Therefore there was no
      difference between control group and zinc-deficient group. A possible reason for
      this is discussed. Zinc deficiency led to a reduction of serum zinc concentration
      and alkaline phosphatase activity as well as to changes in the antioxidant system
      of erythrocytes characterized by a decrease of glutathione and an increase of
      glutathione S-transferase activity. Superoxide dismutase activity in serum
      decreased. There was no indication for hemolysis in vivo and for liver injuries.

PMID- 9272225
TI  - Superoxide anion radical mediated dissection of rat sperm: an in vitro study.
AB  - Sperm is highly sensitive to superoxide radical surge in the granuloma interior.
      To investigate possibility of a superoxide radical bomb, the role of an
      oxyradical on the spermatozoon was studied in vitro using potassium superoxide, a
      potent superoxide radical producer. Results confirm that the superoxide radical
      has a unique site-specific scissoring power.

PMID- 9272224
TI  - A novel method for evaluating the acrosomal status of mammalian spermatozoa.
AB  - A novel method was developed to evaluate the acrosomal status of mammalian
      spermatozoa. The method is based on the ability of the lectin Pisum sativum
      agglutinin (PSA) to bind specifically to glycoproteins of the acrosomal matrix
      released during the acrosome reaction. The amount of released acrosomal content
      is proportional to the fraction of spermatozoa that underwent acrosome reaction.
      The released glycoproteins present in the supernatant separated from the cells
      were detected via an ELISA-like assay. The authors suggest that one of these
      glycoproteins might be the acrosin as identified by anti-acrosin antibodies,
      using Western blot analysis. The new method (demonstrated here with ram and bull
      spermatozoa) correlates well with the results obtained by conventional methods.
      Its advantages are simplicity, objectiveness, rapidity, and low cost. In
      addition, many samples can be processed in parallel. The method can be used in
      experimental as well as clinical applications.

PMID- 9272226
TI  - Epididymal influence on acquisition of sperm motility in the gekkonid lizard
      Hemidactylus flaviviridis.
AB  - Total sperm count and percent sperm motility were noted in different parts of the
      epididymis, and the effect of anterior, middle, and posterior epididymal fluid on
      the induction of motility of nonmotile testicular spermatozoa was observed. The
      results were used to compare the influence of different parts of epididymis of
      Hemidactylus flaviviridis on the acquisition of sperm motility, which is a sign
      of sperm maturation. Spermatozoa collected from different regions of the ductus
      epididymidis showed considerable difference in their motility as well as total
      count with an increase from anterior to posterior region. The epididymal fluids
      from different regions induced the motility of testicular spermatozoa and the
      induction accelerated with increasing fluid volume and incubation period.
      Epididymal fluid at higher volumes induced the motility of nonmotile testicular
      spermatozoa significantly even at short-term incubation. Among different
      epididymal regions, fluid from posterior was more potent in influencing the
      motility than the fluids of middle and anterior. Motility pattern of spermatozoa
      varied from zig-zag, circular, and erratic in anterior to wavy in posterior
      region of epididymis. However, the mean sperm velocity did not show any regional
      variation.

PMID- 9272227
TI  - Assessment of the relationship of sperm morphology with seminal and other
      clinical conditions of semen donors.
AB  - The occurrence of abnormal forms of spermatozoa in human semen is quite common.
      According to WHO, semen is considered normal even if it contains 50%
      morphologically abnormal spermatozoa. This study assessed whether the sperm
      morphology maintains any relation with the relevant clinical conditions of the
      semen donor. One hundred samples representing normal and different types of male
      factor etiologies underwent semen and morphological analysis. Clinical
      information such as race, age, weight, profession, medication, medical history,
      and smoking habit of the semen contributors were recorded. The influence of
      seminal and clinical features on sperm morphology was evaluated with multiple
      regression analysis. Head abnormalities were more common than tail abnormalities.
      Acrosomal defects and coiled tails were the most prevalent head and tail
      abnormalities, respectively. Regression analysis failed to confirm any strong
      association between sperm morphology and other seminal parameters. Accessory
      gland-related seminal parameters such as viscosity, volume, pH, and liquefaction
      showed the least association with the morphological variability. Sperm morphology
      also showed poor correlation with race, age, weight, smoking habit, and work
      environment.

PMID- 9272228
TI  - Assessment of the quality of frozen serum by spectrophotometric analysis and
      sperm bioassay.
AB  - Serum is an integral part of media used for in vitro fertilization (IVF) and
      andrology work. Previous studies showed that the IVF results could benefit if
      sera were screened for deleterious effects before use. Such screening is
      impractical when fresh sera are used but may be feasible if the serum is frozen
      prior to use. This study assessed the impact of freezing on the quality of serum.
      A total of 158 serum samples, prepared in a university-based andrology-IVF
      center, were included in the study. The frozen sera were thawed in batches to be
      used in a series of laboratory experiments. Serum quality was evaluated by
      spectrophotometric analysis and sperm bioassay under several defined conditions:
      fresh, frozen, pre- and postfiltration, pre- and postcentrifugation, and the
      patients' fertility condition. Although all sera were filtered through 0.22
      micron filter, more than 10% frozen sera required 0.4- or a combination of 0.8-
      and 0.4-micron filters before they could be passed through the 0.22-micron
      filter. Frozen sera that were directly filtrable with a 0.22-micron filter lost
      13% turbidity upon filtration. The turbidity of the frozen sera were higher
      compared to fresh ones as revealed by optical density (OD) and relative light
      scattering (RLS) spectrophotometry. The freeze/storage-induced spectrophotometric
      changes did not correlate with the storage time. The centrifugation caused
      precipitation of sera components. The rate of precipitation of the serum
      components correlated with the duration of freezing. Spectrophotometric analysis
      and sperm bioassay did not differentiate the sera of pregnancy-positive and
      pregnancy-negative subjects. The sperm bioassay failed to detect any biological
      impact of freezing-induced spectrophotometric changes in the sera, suggesting
      that the freezing-induced changes did not significantly diminish the serum's
      capability of supplementing the culture media.

PMID- 9272229
TI  - Free radical mediated sperm-load management in the vagina of rats.
AB  - The postcoitus phagocytic engulfment of spermatozoa following disintegration of a
      sperm cell has not been well understood until now. By monitoring the free radical
      status of the vagina in accordance with the various stages of the estrous cycle
      and the sperm-cutting power of vaginal flushing, a positive correlation has been
      detected that favors the superoxide theory of the sperm-cutting technique in
      vivo. This finding is also consistent with the previous experience of free
      radical bombing of spermatozoa in spermatic granuloma.

PMID- 9272230
TI  - Microarchitecture of the cat testis with special reference to Leydig cells: a
      three-dimensional study by alkali maceration method and scanning electron
      microscopy.
AB  - Testes from adult cats were studied by means of parallel transmission and
      scanning electron microscopy (SEM) after NaOH digestion technique, which
      selectively removed connective tissues or cells. The testis is covered by a dense
      fibroconnective tunica albuginea that partially divides the organ in lobules by
      sending septa into the parenchyma. The lamina propria of the seminiferous tubules
      consisted of one or two rows of cells. The interstitium was made up of randomly
      arranged collagen bundles. The most significant feature was the numerous Leydig
      cells rich in lipid droplets and displaying epithelioid features. Following
      alkali digestion and SEM these cells showed a cord-like arrangement. The cords
      were formed by one or two closely apposed cells, in between which some
      labyrinthine or canalicular-like spaces were left that in some areas opened in
      wide perivascular spaces. This particular arrangement of Leydig cells and the
      labyrinthine intercellular spaces is very likely designed to improve cell
      secretion of hormones, facilitating their transport into the blood, as well as
      the traffic of fluids and metabolites. The present techniques allowed the
      visualization of a real three-dimensional testicular microarchitecture and
      microtopography, not detectable with other methods. Such a study may help to
      better highlight the testicular morphophysiology.

PMID- 9272231
TI  - Ultrastructural characteristics of Gardnerella vaginalis infection in the
      heterosexual couple.
AB  - Adhesion and penetration of Gardnerella vaginalis into the male urethral and
      female vaginal epithelial cells were evaluated in a prospective cohort study of
      infected females and their sexual partners. Vaginal secretions of 10 women with
      culture proven G. vaginalis infection and semen samples of their asymptomatic
      husbands were analyzed with conventional optical and electron microscopy. G.
      vaginalis was isolated in 50% of the male sexual partners of women harboring the
      microorganism. G. vaginalis adheres to the plasmatic membrane and penetrates into
      the cytoplasm of both vaginal and urethral epithelial cells. The ability of G.
      vaginalis to colonize the male lower genital tract may have clinical relevance
      with respect to the role of the male partner in the reinfection of women.

PMID- 9272233
TI  - hCG stimulation test for diagnosis of androgen deficiency.
AB  - A diagnostic-stimulation test with hCG (Pregnyl, Organon) was developed for
      demonstration of latent testicular deficit. The test was worked out on clinically
      healthy men and was used to diagnose cases of anorchidism and cryptorchidism.
      This stimulation test may be applied in clinical andrology as a noninvasive and
      highly sensitive method.

PMID- 9272232
TI  - Effect of acupuncture on sperm parameters of males suffering from subfertility
      related to low sperm quality.
AB  - The aim of this prospective controlled study was to assess the effect of
      acupuncture on the sperm quality of males suffering from subfertility related to
      sperm impairment. Semen samples of 16 acupuncture-treated subfertile patients
      were analyzed before and 1 month after treatment (twice a week for 5 weeks). In
      parallel, semen samples of 16 control untreated subfertile males were examined.
      Two specimens were taken from the control group at an interval of 2-8 months. The
      expanded semen analysis included routine and ultramorphological observations. The
      fertility index increased significantly (p < or = .05) following improvement in
      total functional sperm fraction, percentage of viability, total motile
      spermatozoa per ejaculate, and integrity of the axonema (p < or = .05), which
      occurred upon treatment. The intactness of axonema and sperm motility were highly
      correlated (corr. = .50, p < or = .05). Thus, patients exhibiting a low fertility
      potential due to reduced sperm activity may benefit from acupuncture treatment.

PMID- 9272234
TI  - Post-treatment of transient focal cerebral ischemia in rats with the novel
      cerebrovascular-selective Ca2+ channel antagonist (+/-)-(E)-1-(3-fluoro-6,11
      dihydrodibenz[b,e]-oxepine-11-yl)-4-(3-pheny l-2-propenyl)-piperazine dimaleate.
AB  - The efficacy of post-ischemic treatment with AJ-3941 ((+/-)-(E)-1-(3-fluoro-6,11
      dihydrodibenz[b,e]-oxepine-11-yl )-4-(3-phenyl-2- propenyl)-piperazine dimaleate,
      CAS 143110-70-7), a cerebrovascular selective Ca2+ channel antagonist, on brain
      infarction induced by focal ischemia-reperfusion in rats was evaluated. Focal
      ischemia was induced by transient occlusion of middle cerebral artery (MCA) with
      a 3-0 nylon monofilament for 90 min. One day after MCA occlusion (MCAo), brain
      infarct size was determined by measuring 2,3,5-triphenyltetrazonium chloride
      negative stained area of the serial brain sections. The development of cerebral
      infarction was observed in both regions of cortex and subcortex, such as
      striatum, caudatum, putamen, hippocampus and corpus callosum. Post-ischemic
      treatment with AJ-3941 (1 or 3 mg/kg p.o., 10 min and 3 h after the occlusion)
      significantly reduced the infarct size and volume in the ipsilateral hemisphere
      in a dose-dependent manner, compared to the solvent control. The reducing effect
      was observed mainly in the cortical region, and a significant reduction of the
      subcortical infarct volume was found at the higher dose (3 mg/kg). Post-ischemic
      treatment with the thromboxane A2 synthetase inhibitor, sodium ozagrel (150
      micrograms/kg/min i.v. infusion, between 1 h and 24 h after the MCAo) did not
      reduce the infarct volume in the hemisphere after ischemia-reperfusion. AJ-3941
      had only minimum effect on the elevation of body temperature during ischemia
      reperfusion. These results indicate that post-ischemic treatment with AJ-3941 may
      ameliorate the brain injury after the transient focal cerebral ischemia, and they
      suggest that AJ-3941 has beneficial effects for treatment of ischemic cerebral
      damage, such as stroke.

PMID- 9272235
TI  - Modulation of pharmacological profile of diphenylethane (lefetamine-type)
      derivatives.
AB  - With the aim to split the pharmacological properties of lefetamine (CAS 14148-99
      3), some structural modifications of this compound have been studied. The basic
      group of lefetamine has been shifted from the alkyl chain to the vicinal phenyl
      ring and the N-substitution has been changed. The dimethylaminomethyl derivatives
      and chiefly the o-morpholinometyhl exhibited a strong anti-visceral chemical
      antinociception activity stripped of thermal antinociception properties and
      physical dependence liability. Furthermore, through the introduction of a
      diethylaminomethyl group in the lefetamine structure some derivatives were
      selected exhibiting besided a significant increase in the anti-visceral chemical
      antinociception activity, remarkable local anesthetic properties.

PMID- 9272236
TI  - Cardiovascular and antiarrhythmic effects of the azulene-1-carboxamidine
      derivative N1,N1-dimethyl-N2-(2-pyridylmethyl)-5-isopropyl-3, 8-dimethylazulene-1
      carboxamidine.
AB  - The azulene-1-carboxamidine derivative N1,N1-Dimethyl-N2-(2- pyridylmethyl)-5
      isopropyl-3,8-dimethyl-azulene-1-carboxamidine (CAS 186086-10-2, HNS-32) is a
      newly synthesized compound. In the present study, direct cardiovascular effects
      of HNS-32 were assessed using the canine isolated, blood-perfused sinoatrial
      node, papillary muscle and atrioventricular node preparations, while the
      antiarrhythmic action was examined using the canine two-stage coronary ligation
      induced arrhythmia model. Intracoronary administration of HNS-32 (1-300
      micrograms) suppressed the sinus nodal automaticity and ventricular contractile
      force, while it increased the atrio-His and His-ventricular conduction time as
      well as the coronary blood flow. Intravenous administration of HNS-32 (5 mg/kg)
      suppressed the ventricular arrhythmia for approximately 30 min. Since HNS-32
      possesses multiple cardiac direct effects which are unique compared with well
      established antiarrhythmic drugs, it may become a leading compound in the search
      for novel antiarrhythmic agents.

PMID- 9272237
TI  - Studies on psychomotoric effects and pharmacokinetic interactions of the new
      calcium sensitizing drug levosimendan and ethanol.
AB  - Levosimendan (CAS 141505-33-1) is a calcium sensitizing drug intended for the
      treatment of congestive heart failure. In animal experiments levosimendan has
      potentiated the sedative effects of ethanol. Due to poor water solubility of the
      compound, ethanol is used as a diluent in the intravenous formulation. In this
      study the possible interactions between levosimendan and ethanol in human have
      been studied. Twelve healthy male volunteers were included in this double-blind,
      randomized, cross-over study. The study consisted of three treatment periods:
      levosimendan 1 mg intravenously, levosimendan combined with ethanol orally and
      ethanol 0.8 g/kg alone. Blood samples for determination of levosimendan and
      ethanol concentrations were collected for 8 h after the dosing. To observe
      possible pharmacodynamic interactions psychomotoric tests were made before drug
      administration and 1h, 2h, 3h and 6h thereafter. These tests included Digit
      symbol substitution test, Maddox wing, Critical Flicker fusion and VAS-test for
      subjective assessment of performance status. Plasma levosimendan concentrations
      were not changed by the concomitant ethanol administration. Ethanol did not alter
      the pharmacokinetics of levosimendan except the volume of distribution of central
      compartment which was decreased. Levosimendan did neither affect elimination of
      ethanol. Levosimendan did not potentiate the psychomotoric effects of ethanol
      neither did it have any psychomotoric effects itself. In conclusion, levosimendan
      is not likely to have any psychomotoric adverse effects or any clinically
      significant interactions with ethanol.

PMID- 9272238
TI  - Salicylate levels in rat stomach tissues after administration of aspalatone and
      acetylsalicylic acid in relation to their ulcerogenicity.
AB  - To study the mechanism for the low ulcerogenicity of the antithrombotic agent
      aspalatone ([3-[2-methyl-4-pyronyl)]-2-acetyloxybenzoate, CAS 147249-33-0), the
      metabolism and disposition of aspalatone were compared with those of
      acetylsalicylic acid (ASA) in the gut wall in relation to the salicylate level in
      the stomach tissues following oral administration in pyrolus-ligated rats. Both
      aspalatone and ASA were essentially stable in gastric juice and were absorbed in
      stomach unchanged. In glandular portion of the stomach, salicylate level found at
      10 min post-dose in aspalatone (80 mg/kg)-and in ASA (50 mg/kg)-treated group was
      67 +/- 43 nmol/g tissue and 2000 +/- 250 nmol/g tissue, respectively. In non
      glandular (rumen) tissue, salicylate was not detected in the aspalatone group,
      whereas it reached a concentration of up to 1100 +/- 130 nmol/g tissue in the ASA
      group. As a result of the relative stability of the ester bond connecting the
      salicylic acid and maltol groups towards hydrolysis in the stomach and entrapment
      of ASA due to ion trapping, a lower salicylate level was observed in the stomach
      after oral aspalatone administration, and this may, at least in part, be the
      underlying mechanism for the low ulcerogenicity of aspalatone.

PMID- 9272239
TI  - Experimental animal studies on the hypoglycemic effects of a Copalchi extract.
AB  - The hypoglycemic effect of a Copalchi extract (Sucontral) was tested in 60 adult
      male and female-Wistar rats in the present randomized, placebo-controlled,
      parallel-comparative animal study. A control group receiving only an Altromin
      standard chow was compared to treatment groups which received an Altromin chow
      enriched with Copalchi dry substance at 0.028% m/m or at 0.28% m/m. The study
      period was 30 days. The distinctly significant blood glucose lowering effect of
      the Copalchi extract could be demonstrated in both treatment groups. No
      significant difference in the antidiabetic effect was seen between the two
      concentrations. The onset of action of the Copalchi extract was observed between
      treatment day 1 and 3. A 20-25% decrease in the blood glucose concentration was
      achieved between the 7th and 15th day of treatment and remained at this level
      thereafter. This plateau was reached in the female rats already between treatment
      day 3 and 5. The parallel observed increase in the mean body weight was not
      striking and generally was the same between the test animals and the control
      animals.

PMID- 9272240
TI  - Studies on analgesic and anti-inflammatory activities of 1-dialkylaminomethyl-2
      (p-substituted phenyl)-5-substituted benzimidazole derivatives.
AB  - In this study the analgesic and anti-inflammatory activity of 1,2,5
      trisubstituted benzimidazole derivatives have been examined. Analgesic activities
      of these compounds were investigated by using the modified Koster test. Among the
      compounds synthesized especially compound 1g (1-diethylaminomethyl)-2-(p
      chlorophenyl)-5-nitro benzimidazole hydrochloride) has shown higher activity than
      acetylsalicylic acid (ASA) and indometacin. Compound 1e (1-(diethylaminomethyl)-2
      (p-methoxyphenyl)-5-nitro benzimidazole hydrochloride, 1f (1-(diethylaminomethyl)
      2-(p-tolyl)-5-nitro benzimidazole hydrochloride and 1i (1-(pipenridinomethyl)-2
      (p-methoxyphenyl)-5-nitro benzimidazole hydrochloride) proved as potent as the
      standard ASA. Therefore the compounds 1e, 1f, 1g and 1i were screened for their
      anti-inflammatory activities using the carrageenan-induced hind paw edema test.
      Except 1g all compounds were almost inactive against this model of inflammation
      compared to indometacin.

PMID- 9272242
TI  - Evaluation of the drug monitoring programme of azelastine hydrochloride nasal
      spray in the treatment of allergic rhinitis in children under 13 years of age.
AB  - The efficacy and safety of a nasal spray containing azelastine (CAS 58581-89-8;
      e.g. Afluon, Allergadil, Rhinolast) in the treatment of both perennial and
      seasonal allergic rhinitis have been evaluated in two postmarketing drug
      surveillance programmes (PMS) conducted in Spain. The present analysis reports on
      the data from a subpopulation from these studies and includes 211 children aged
      less than 13 years of age. In 73% of children the administered dose of azelastine
      was one spray puff per nostril twice daily, corresponding to the recommended
      daily, dosage of 0.56 mg azelastine. Patients with seasonal rhinitis were treated
      for a period of two weeks, those perennial rhinitis were treated for four weeks.
      The efficacy of the azelastine was assessed by the changes in severity of the
      following 10 individual symptoms of rhinitis: sneezing, nose itching, nose
      congestion, rhinorrhoea, smell reduction, eye itching, lachrimation, photophobia,
      throat itching, and coughing. Symptoms were rated according to a four-point
      scale: 0 = absent, 1 = slight, 2 = moderate, and 3 = severe. Both the
      investigators and the patients were requested to evaluate efficacy and tolerance
      according to a four point scale: 1 = very good, 2 = good, 3 = moderate, 4 = bad.
      All of the 10 clinical symptoms underwent a statistically significant and
      clinically relevant reduction during the treatment period. Nose itching,
      sneezing, and rhinorrhoea were the symptoms which completely disappeared in the
      highest number of patients by the end of therapy. The mean sum of all 10 symptom
      scores pre-treatment (baseline visit) was 11.03 while at the completion of
      therapy (control visit) it was 3.21. Overall, a decrease of this score was seen
      in 112 (98%) patients for whom complete data was available, whereas an increase
      was registered only in 2 (2%) cases. The mean total of the five nasal scores at
      the baseline visit was 7.64, and at the control visit its value measured 2.31.
      One hundred and twenty-one (98%) patients exhibited a decrease in the total nasal
      score, and only 3 (2%) demonstrated an increase. The mean total of the three
      ocular symptoms scores at the baseline visit was 2.25, while at the control visit
      its value was only 0.48. A decrease in the total ocular score was observed in 78
      (62%) patients, while an increase occurred in only one patient. Overall, 85% of
      doctors evaluated the efficacy of the drug as "very good/good". 90% of patients
      did not report adverse events (AEs) during treatment with azelastine and only
      four patients discontinued treatment due to AEs. General tolerance was evaluated
      as "very good or good" by 97% of the treating physicians. Local tolerance was
      rated as "very good or good" by 94%. The most positive characteristics of the
      therapy according to the physicians were: rapid onset of action in 56% of cases,
      good efficacy in 46%, simple application in 44%, no sedation in 34%, and long
      duration of action in 22% of cases. Based upon the excellent risk-benefit
      assessment of this PMS, our results confirm the suitability of azelastine nasal
      spray in the treatment of allergic rhinitis in juvenile patients.

PMID- 9272241
TI  - Effect of Apafant on bronchial hyperresponsiveness and down-regulation of beta
      adrenoceptors induced by endotoxin in guinea pigs.
AB  - Intraperitoneal injection of endotoxin resulted in bronchial hyperreactivity to
      histamine in guinea pigs. In addition, endotoxin (lipopolysaccharide, LPS) caused
      a decrease in the relaxation of the lung parenchymal strips induced by the beta
      adrenoceptor agonist, isoproterenol (isoprenaline), and a reduction in the number
      of beta-adrenergic binding sites in the lung membrane preparation in guinea pigs.
      Apafant (CAS 105219-56-5, WEB 2086) was effective in the prevention of endotoxin
      induced changes, i.e., bronchial hyperreactivity to histamine, a decrease in the
      relaxation of lung parenchymal strips induced by isoproterenol and a reduction in
      the number of beta-adrenergic binding sites in the lung membrane preparation in
      guinea pigs. Ketotifen and ozagrel also prevented the bronchial
      hyperresponsiveness and endotoxin-induced deterioration of the beta-adrenergic
      system. No remarkable effect was observed with cromolyn sodium and salbutamol in
      the bronchial hyperreactivity to histamine induced by endotoxin in guinea pigs.
      Cromolyn sodium also caused no influence on the down-regulation of beta
      adrenoceptors.

PMID- 9272243
TI  - Effect of the histamine H2-receptor antagonist (+/-)-(E)-1-[2-hydroxy-2-(4
      hydroxyphenyl)ethyl]-3'-[2-[[[5-methylamino ) methyl-2-furyl] methyl]thio]ethyl]
      2"-(methylsulfonyl)guanidine on acute gastric mucosal injury in rats and its free
      radical scavenging activities.
AB  - The protective effect of T-593 ((+/-)-(E)-1-[2-hydroxy-2-(4-hydroxyphenyl)ethyl]
      3'-[2-[[[5-(methylamino) methyl-2-furyl]methyl]thio]ethyl]-2"
      (methylsulfonyl)guanidine, CAS 140695-21-2), a new histamine H2-receptor
      antagonist, was investigated in rats with acute gastric mucosal injury. An
      ischemic injury followed by reperfusion was produced by applying a small vascular
      clamp to the celiac artery for 30 min and then removing it for 60 min. T-593
      significantly reduced the area of the lesion in the stomach in a dose-dependent
      manner, and doses of 0.3 and 3.0 mg/kg inhibited the increase of lipid peroxides
      in the gastric mucosa after ischemia-reperfusion. A spin-trapping method using
      5,5-dimethyl-1-pyrroline-N-oxide showed that T-593 scavenged hydroxyl radicals
      generated by the hydrogen peroxide-ferrous iron sulfate system. T-593 also
      significantly inhibited the increase of lipid peroxides induced by free-radical
      initiators in gastric mucosal homogenates. Thus, the protective effect of T-593
      against acute gastric mucosal injury induced by ischemia and followed by
      reperfusion may result, in part, from its antioxidant properties.

PMID- 9272244
TI  - Mixed antisecretory and gastroprotective activities of a new H2-antagonist
      containing a nitric oxide-donor furoxan moiety.
AB  - The effect of a new histamine H2-receptor antagonist derived from the lamtidine
      molecule and containing a nitric oxide (NO)-donor furoxan moiety (derivative 1)
      was studied for its gastric antisecretory activity and for a possible
      gastroprotective effect, in comparison with the analog without the furoxan moiety
      (derivative 2). The H2-receptor antagonistic activity was also investigated in
      the isolated guinea pig papillary muscle. Derivative 1 was approximately 10 times
      less potent than derivative 2 at the H2-receptor level; conversely, it was about
      10 times more effective as a gastroprotective agent against ethanol- and 0.6 N
      HCl-induced gastric lesions. The mechanism of the gastroprotection exerted by
      derivative 1 is probably connected with the release of NO, whose vasodilating
      action on gastric mucosa vessels is crucial. The combined antisecretory and
      gastroprotective activity of derivative 1 allows this compound to be considered
      as a prototype of a new class of antiulcer agents.

PMID- 9272245
TI  - Pharmacokinetics of estradiol and of estrone during application of three
      strengths of an estradiol transdermal patch with active matrix.
AB  - The pharmacokinetic pattern of estradiol (CAS 50-28-2) and of estrone (CAS 53-16
      7) during and after application of three strengths of a new transdermal estradiol
      patch (Dermestril) with active matrix was investigated in a cross-over study in
      24 women in natural or surgical menopause. Free estradiol and estrone were
      assayed by GC-MS on plasma samples obtained during a 4-day application on the
      upper buttocks of the patches with 3 strengths and release rates of 25, 50 and
      100 micrograms/day estradiol. The estradiol concentrations in plasma increased
      from 0-10 pg/ml typical of menopause to average concentrations of 23, 40 and 79
      pg/ml during the application of the new estradiol transdermal patches with the
      three strengths. The concentrations of estradiol are in the range of those during
      the early follicular phase in women in fertile age. The increases were linearly
      related with the strength of the patches. Upon removal of the patches the
      estradiol concentrations returned to the basal low values in 8-24 h. Retarded
      with regard to estradiol, there was also an increase of estrone, from basal
      average concentrations of 22-32 pg/ml up to 31, 39 and 60 pg/ml. The increase of
      estrone was less pronounced than that of estradiol. Also estrone returned to its
      basal concentrations 24 h after removal of the patches. The estradiol/ estrone
      ratio from very low values typical of postmenopause increased to values of about
      1, i.e. in the range of those found during the fertile age of woman. The adhesion
      of the patches was satisfying, provided that direct rough frictions were avoided.
      The patches were locally well tolerated, with rare mild and transient irritating
      effects on the skin. Also the systemic tolerability was good, with occasional
      mild or moderate side effects typical of estradiol (headache, mastodynia and
      pelvic heaviness) which in the practical use can be easily avoided by the
      application of patches of lower strength.

PMID- 9272246
TI  - Intracellular activity of azithromycin against Mycobacterium avium complex in
      human macrophages.
AB  - In the concentration range examined (0.5-16 micrograms/ml) the azalide antibiotic
      azithromycin (CAS 83905-01-5, Zithromax) inhibited the growth of mycobacteria in
      macrophages over 7 days. The higher concentrations of azithromycin, 8 and 16
      micrograms/ml, reduced the number of phagocytized bacteria in macrophages by at
      least 1 log unit within 4 days. The system used, macrophages from healthy
      volunteers, is suitable for testing the intracellular activity of drugs against
      the Mycobacterium avium complex.

PMID- 9272247
TI  - Safety pharmacology of a combination of tinidazole and oxyphenonium bromide.
AB  - The effect of a combination of 150 mg tinidazole (CAS 19387-91-8) and 1 mg
      oxyphenonium bromide (CAS 50-10-2), referred to as the combination, was examined
      in various animal species to assess its safety. In mice and rats, the combination
      in the dose range 30-1000 mg/kg p.o. or 250 mg/kg i.p. did not produce
      behavioural or neurological changes, nor did it influence pentobarbital sleeping
      time, though, alcohol sleeping time was altered. In anaesthetised dogs, neither
      blood pressure, ECG, heart rate, respiration or gastrointestinal motility was
      affected after single intraduodenal administration of the combination 20 and 50
      mg/kg or after chronic oral administration of 25 mg/kg daily for 15 days. In
      isolated organs, viz. perfused rabbit heart, guinea-pig ileum and rat ileum no
      significant changes were observed following various doses of the combination,
      compared to tinidazole and oxyphenonium bromide given alone in corresponding
      concentrations. In conclusion, the pharmacological profile of the aforementioned
      combination in the dosages employed in mice, rats, guinea-pigs, rabbits and dogs
      shows that it is safe and well tolerated.

PMID- 9272248
TI  - Physico-chemical properties and stability of the new hypoxia-selective agent 7
      chloro-3-[[N,N-dimethylamino)propyl]amino]-2-quinoxalinecarbonitrile 1,4-di-N
      oxide hydrochloride.
AB  - 7-Chloro-3-[[N,N-dimethylamino)propyl]amino]-2-quinoxalinecarbonitril e 1,4-di-N
      oxide hydrochloride (Q-85 HCl), a new hypoxia-selective agent, was studied to
      clarify its physico-chemical properties. Melting point, spectra (UV, IR, NMR,
      MS), thermal behaviour, solubility, pKa, partition coefficient and
      chromatographic characteristics (TLC, HPLC) have been determined. The stability
      of Q-85 HCl was studied under various conditions by HPLC. Q-85 HCl in solid state
      was very stable to heat and fairly stable to light. Some degradation products of
      Q-85 HCl were identified in basic solution.

PMID- 9272249
TI  - Studies of the incidence of spontaneous pancreatic tumours in ageing CD rats.
AB  - A survey of the incidence of spontaneous pancreatic tumours in CD rats was
      carried out. The survey revealed islet cell adenomas to be the most common of
      pancreatic tumours with a higher incidence in untreated males (11.7% in
      comparison to in females 5.5%). 9040 untreated and 24578 treated rats were
      included in this survey. These rats were from two year carcinogenicity studies
      over a 15 year period. The sex difference appeared also in the incidence of islet
      cell carcinoma (males 2.4% vs females 1%). The third type of tumour was exocrine
      adenoma with an incidence of 2% in males, 0.1% in females. The last type, which
      was very rare in this strain, was exocrine carcinoma (0.08% in males, 0.02% in
      females). The tumour incidences were more in rats killed at termination than in
      those died or killed earlier during the study suggesting a late onset of these
      tumours. Exocrine carcinoma was rarest of all pancreatic tumours. In contrast to
      man, rat pancreatic tumours were not life-threatening in rats, except for
      exocrine carcinoma. Pancreatic tumours are somewhat age-related as they were very
      rare in young rats and appeared mainly in rats over 70 weeks of age. Cystic
      exocrine adenoma, cystic or duct exocrine adenocarcinoma reported in man, were
      not seen in rats. Exocrine tumours are fatal tumours in man with very poor
      prognosis. Pancreatic carcinomas in rats mostly showed only local invasion. On
      very rare occasions they showed metastasis in to liver, lung and bone marrow.
      Ductal/cystic exocrine carcinoma of man showed metastasis to liver,
      peripancreatic lymph nodes, lymphatics, skeletal muscle and the lung. Exocrine
      adenocarcinoma in man was twice as common in males as in females, comparable to
      the general incidence of pancreatic tumours in rats. Islet cell tumours in man
      show no clear difference between males and females which is in contrast to rats.
      Both in man and in rats pancreatic tumours appear to occur in the latter half of
      life span.

PMID- 9272250
TI  - Symmetry-based HIV protease inhibitors containing (S,S) or (R,R) tartaric acid
      core structure.
AB  - Two series of symmetry-based HIV protease inhibitors containing (S,S) or (R,R)
      tartaric acid core structure were prepared and tested for inhibitory property
      against the enzyme. All compounds showed weak antiprotease activity.

PMID- 9272251
TI  - Continuing the debate on a separate adolescent psychiatry.
AB  - OBJECTIVE: This paper continues the debate, started by George Patton, that a
      separate adolescent psychiatry is required since many psychotic illnesses begin
      in late adolescence, and adolescent mental health needs have not been well met by
      child or adult psychiatry. METHOD: Epidemiological studies are used to illustrate
      that there are many continuities, as well as discontinuities, in the natural
      history of psychiatric disorders throughout the life cycle. The paper comments on
      rational service planning, which requires data on the outcomes of different
      treatment approaches. It goes on to explore the implications of a separate
      adolescent psychiatry for service delivery, including how current service
      boundaries and the training of psychiatrists might need to change. RESULTS AND
      CONCLUSIONS: An argument is mounted that psychiatrists should take a whole life
      perspective, rather than further fragment the specialty. In most Australian
      States, recent reviews of child and adolescent mental health services are likely
      to result in increased funding for services to adolescents. Adult psychiatry
      needs to attend more to the requirements of older adolescents, and greater
      collaboration is recommended between psychiatry services for children and adults.
      The authors argue for diversity of approaches, and consider that moves towards
      separate adolescent mental health services may not always be appropriate.

PMID- 9272252
TI  - Intellectual handicap in contemporary psychiatry.
AB  - OBJECTIVE: To apprise readers of the 'state of play' in the psychiatry of
      intellectual handicap. METHOD: A review was conducted of relevant journals and
      conference abstracts covering a range of scientific aspects of intellectual
      disability. Those developments considered to be most significant were summarised.
      In addition, consideration is given to issues relevant to the politics of
      disability affecting psychiatric practice in Australia. RESULTS: There have been
      considerable developments in our understanding of the pathogenesis of
      intellectual handicap in pharmacotherapy and the behavioural therapies, in the
      taxonomy of psychopathology, in epidemiology, in delineation of behaviour
      phenotypes, and in assessment and measurement of psychopathology. CONCLUSION:
      Intellectual handicap and psychiatry have had a chequered relationship in
      Australia, but the two fields are now clearly moving again to a closer and more
      productive collaboration. Recent scientific advances have provided a stimulating
      environment for this increased activity and interest.

PMID- 9272253
TI  - Sixty years of psychosurgery: its present status and its future.
AB  - After its introduction 60 years ago, psychosurgery witnessed a remarkable rise
      followed by a decline. In the 1990s, it is a marginal treatment practised by a
      few psychiatrists in some specialised centres around the world. The psychiatric
      profession, however, continues to support it, and there is some evidence for a
      recent renewal of interest in the procedure. In this paper, the reasons for this
      reluctant acceptance of psychosurgery are examined, and the factors that are
      likely to determine its future are identified. The profession is urged to keep
      the interest in psychosurgery alive until further theoretical and empirical
      developments can either announce its death or lead to a resurgence of psychiatric
      neurosurgery in its present or modified form.

PMID- 9272254
TI  - A prospective psychotherapy outcome study.
AB  - OBJECTIVE: To assess the outcome of 31 patients treated in a day and semi
      residential psychotherapy setting. METHOD: Patients had moderate to severe
      personality difficulties and were referred when current therapy was insufficient
      or because of the severity of their problems. Eighty-one percent had a Cluster C
      and 19% a Cluster B (Borderline) Personality Disorder diagnosis (DSM-III-R).
      Therapy was psychodynamically and feministin-formed and included a sociopolitical
      dimension. Rating scales used were the Symptom Checklist 90, Goal Attainment
      Scale, Global Assessment Scale and measures of health resource usage, which were
      completed pre-treatment, post-treatment and at 4-, 12- and 24-month follow-up.
      RESULTS: Mean duration of therapy was 4 months (68 therapy days). All clinical
      rating scales demonstrated marked improvements following treatment (p < 0.0001)
      which were sustained at 2-year follow-up. There were also improvements of health
      resource usage. CONCLUSIONS: The results document the clinical efficacy of
      psychotherapy in this setting, provide support for the philosophy of practice,
      and suggest that psychotherapy outcome can be evaluated at reasonable financial
      cost in many settings.

PMID- 9272255
TI  - Gender, race and poverty: bringing the sociopolitical into psychotherapy.
AB  - OBJECTIVE: To explore the modification of traditional psychotherapy to provide a
      more relevant service for non-dominant groups including women, Maori and the
      poor. METHOD: The philosophy and practice of a psychotherapy service that made
      overt sociopolitical issues for women, Maori and the poor was analysed and linked
      with literature on psychotherapy for non-dominant groups. RESULTS: Traditional
      psychotherapy, with its focus on the intrapsychic, has not addressed the
      condition of marginalised groups such as the poor, ethnic minorities including
      Maori, and some women, whose mental health difficulties have major contributions
      from external sources. The service analysed, and much of the literature, used
      social analysis as a therapeutic tool to break the cycle of self-blame and doubt
      and to contextualise intrapsychic experience. As non-dominant groups lack power,
      power differences in the therapy relationship should be lessened to avoid
      retraumatising the patient. CONCLUSION: It is possible for psychotherapy to
      broaden its traditional base to include a sociopolitical viewpoint. This would
      make it more available and meaningful to a wider range of people, especially
      those with the double disadvantage of adverse intrapsychic and sociopolitical
      factors.

PMID- 9272256
TI  - The effect of a new integrated mental health service on hospitalisation.
AB  - OBJECTIVE: The purpose of the present study was to partially evaluate a new
      integrated mental health service by monitoring inpatient lengths of stay. We
      hypothesised that the median cumulated length of stay for inpatients would
      decrease, and that the frequency of readmissions would not increase. METHOD: Data
      was collected for two 6-month periods before and after the introduction of an
      integrated mental health service (IMHS). Two functionally identical wards (G and
      E) were studied. Ward G was then integrated with the regional community
      psychiatry service, while Ward E remained non-integrated. RESULTS: Following
      integration, the median cumulative length of stay in the IMHS's Ward G was more
      than halved in comparison with both its own baseline and with the non-integrated
      ward. The average length of stay of overdose patients at the regional general
      hospital that was serviced by the IMHS was also reduced from 2.6 days to 1.5
      days. The non-IMHS ward had a non-significant increase in admissions and no
      change in cumulative length of stay. CONCLUSION: The hypotheses of this study
      were supported by the results. Twelve beds were subsequently closed as a result
      of the efficiencies generated by integration. These findings support the model of
      true integration trailled here.

PMID- 9272257
TI  - Comment: 'as simple as possible, but not simpler'.

PMID- 9272258
TI  - Characteristics of the new long-stay population in an inner Melbourne acute
      psychiatric hospital.
AB  - OBJECTIVE: There has been an accumulation of so-called 'new long-stay' (NLS)
      patients in psychiatric hospitals. To date, no Australian studies have
      characterised this patient group. We aimed to study the demography, and clinical
      and social functioning of the NLS population at Royal Park Hospital (RPH)
      together with patients' attitudes to treatment and views on future placement.
      METHOD: All 30 NLS patients at RPH were identified. Twenty-seven consenting
      patients were assessed using the following standardised instruments: Manchester
      Scale for psychopathology, Life Skills Profile (LSP), Physical Health Index and
      Patient Attitude Questionnaire. Information on past psychiatric history, past
      treatment and current treatment was collected. Insight and compliance were
      assessed. RESULTS: The majority of patients were single men with a diagnosis of
      schizophrenia. Forty-one percent were detained in hospital involuntarily and 56%
      were considered dangerous to themselves or others. The patients were
      characterised by high levels of positive and negative symptoms. They were most
      impaired with respect to 'social contact' relative to the other subscales of the
      LSP. While 10 (48%) patients expressed a desire to leave hospital, only one
      patient considered that anyone would cohabit with them. Over two-thirds
      considered they had been unwell and that medication had helped. Staff rated one
      third as having major problems with compliance. About two-thirds of patients had
      disability secondary to comorbid physical illnesses. CONCLUSION: Like other NLS
      patients studied in the United Kingdom and Ireland, this group had significant
      handicaps secondary to psychiatric illness, concomitant physical illness and
      disability and behaviour unacceptable in community settings. They were also
      characterised by significant social isolation. These factors may be important
      determinants of rehabilitation failure and need to be addressed in the process of
      de-institutionalisation as well as in longitudinal studies examining these and
      other factors predicting NLS status.

PMID- 9272259
TI  - Integrated mental health care: practitioners' perspectives.
AB  - OBJECTIVE: Integrated mental health care (IMHC) is a community-based model that
      considers the patient and informal carers to be the major contributors to stable
      recovery from severe mental health problems. This study investigates the
      implementation of IMHC by 35 New Zealand practitioners 1 year after being trained
      in the model. It also explores their experiences and perceptions regarding the
      model. METHOD: Quantitative and qualitative data were gathered by combining a
      questionnaire survey with in-depth interviews. RESULTS: Few of the trainees had
      been able to implement the model as much as they would have liked. A primary
      barrier to implementation was created by the resource constraints that impede
      most innovative community care initiatives even when demonstrated to be more cost
      effective than traditional hospital-based approaches. Concerns particular to IMHC
      included issues relating to flexibility, time-intensiveness and applicability to
      New Zealand. Many practitioners found some of the specific intervention
      strategies and the clear overall structure of the model useful. Its psychosocial
      emphasis had a positive impact on many practitioners' beliefs about the causes
      and prognosis of severe mental health problems. CONCLUSIONS: Participants offer a
      range of recommendations as to how IMHC might be applied and adapted.
      Consultation with staff, consumers, families and Maori, as well as a
      strengthening of the psychosocial components, are recommended.

PMID- 9272260
TI  - Predicting intentions to seek help from professional mental health services.
AB  - OBJECTIVE: This study investigates the factors related to the intention to seek
      professional help for psychological problems utilising Ajzen and Fishbein's
      theory of reasoned action. Many of the variables identified in previous studies
      can be subsumed within this theory, which emphasises the importance of the
      subjective point of view of the individual. METHOD: One hundred and forty-two
      patients waiting for consultations at a community based general practice
      completed a questionnaire designed to assess the components of this theory as
      they relate to seeking help from mental health professionals. RESULTS: The
      results of this study supported the prediction of the intention to seek help from
      a mental health professional from the variables 'attitude toward the behaviour'
      and 'subjective norm'. However, personal attitudes toward seeking help were found
      to be more important than the approval or disapproval of significant others in
      predicting help-seeking intentions. CONCLUSIONS: Overall, the findings indicate
      that a significant factor influencing people's decisions to utilise professional
      mental health services in Australia may be the belief that mental health
      professionals are not actually able to provide a great deal of help or support
      for people's difficulties.

PMID- 9272261
TI  - Intensive nutritional counselling in bulimia nervosa: a role for supplementation
      with fluoxetine?
AB  - OBJECTIVE: The aims of the paper are to determine whether nutritional counselling
      is associated with an improvement in bulimic symptomatology, whether this
      improvement is maintained during post-treatment follow-up, and whether the
      addition of fluoxetine 3 x 20 mg/day confers additional benefit. METHOD:
      Psychological, pharmacological and combined psychopharmacological treatments of
      bulimia nervosa were reviewed briefly. Sixty-seven patients referred to
      specialist eating disorder services who fulfilled strict diagnostic criteria were
      treated with intensive nutritional counselling and randomly assigned to either
      fluoxetine 3 x 20 mg/day or placebo. After a 1-week 'wash-out', active treatment
      was given over 8 weeks, followed by post-treatment interviews at 12 and 20 weeks.
      RESULTS: Both groups of patients improved significantly during treatment. In some
      respects, the fluoxetine group did slightly better as demonstrated by the items
      'restraint', 'weight concern' and 'shape concern' (p < 0.05 vs p < 0.0001) on the
      Eating Disorder Examination (EDE). Fluoxetine patients decreased their energy
      intake and lost a modest amount of weight. They went on to regain weight during
      the follow-up period, returning to levels higher than they were initially. These
      patients also appeared more likely to have a recurrence of symptoms, as shown by
      the fall in percentage of binge-free patients and by changes in the EDE.
      CONCLUSION: Nutritional counselling is an effective means of treating bulimia
      nervosa, with improvement maintained up to 3 months follow-up. The addition of
      fluoxetine may confer some benefit during active treatment, but its
      discontinuation may contribute to a higher rate of recurrence of symptoms post
      treatment. Of course, this study cannot be extrapolated to the efficacy of
      fluoxetine when used as the only form of treatment in patients for whom intensive
      nutritional counselling or other structured psychological programs are not
      available.

PMID- 9272262
TI  - The use of guardianship legislation for anorexia nervosa: a report of 15 cases.
AB  - OBJECTIVE: This paper investigates compulsory treatment under guardianship
      legislation for 15 anorexia nervosa patients admitted to four eating disorders
      units in New South Wales (NSW), Australia, between 1991 and 1994. METHODS: A
      retrospective follow-up was conducted. This involved an analysis of
      sociodemographic, clinical, eating and weight history, and Guardianship Order
      details obtained from medical records. This small sample was compared to a larger
      sample of anorexia nervosa patients admitted voluntarily to a specialised eating
      disorder unit in NSW. Further follow-up included a structured interview using the
      Morgan-Russell Assessment Outcome Schedule at least 1 year after admission for
      compulsory treatment. RESULTS: For those treated involuntarily, a larger number
      came from metropolitan Sydney and a larger percentage were unemployed, were
      purgers and required specialist medical consultations. A significantly higher
      proportion came from higher socioeconomic groups, and the duration of stay in
      hospital while patients were under guardianship was significantly greater. A high
      degree of comorbidity was noted. There were similarities between those treated
      involuntarily and those treated voluntarily for the source of referral, marital
      status and Body Mass Index on admission and discharge. Only three patients
      accepted a follow-up interview using the Morgan-Russell Outcome Schedule. Two of
      them had made a good recovery. CONCLUSIONS: It was noted that the guardianship
      sample comprised a more severely III group than anorexic patients treated
      voluntarily. The nature of guardianship legislation compared to mental health law
      was discussed and advice offered to clinicians contemplating and implementing
      compulsory treatment.

PMID- 9272263
TI  - Aspects of psychiatric admissions of migrants to hospitals in Perth, Western
      Australia.
AB  - OBJECTIVE: Recent Australian Government initiatives have emphasised problems with
      service provision to the ethnic mentally ill. This study aims to address the
      paucity of contemporary data describing the disposition of the ethnic mentally
      ill in hospital settings. METHOD: Patterns of admissions for psychiatric
      disorders to all hospitals in Perth, Western Australia, for the 3 years from 1990
      to 1992, of migrants and the Australian born were compared using data from the
      Western Australian Mental Health Information System. RESULTS: The overall rates
      for European migrants showed a 'normalisation' towards those of the Australian
      born. There were high rates for the schizophrenic spectrum disorders in Polish
      and Yugoslavian (old terminology) migrants. There were low admission rates for
      South-East Asian migrants, predominantly those from Vietnam and Malaysia. Rates
      for alcoholism were low in Italian and all Asian migrants. There were high rates
      of organic psychosis, especially in those older than 75 years, among the Italian
      and Dutch migrants. The relative risk of a first admission in the 3 years being
      an involuntary admission to a mental hospital was almost twice that of the
      Australian-born for migrants from Poland, Yugoslavia, Malaysia and Vietnam.
      CONCLUSIONS: The results imply the possibility of significant untreated and/or
      undiagnosed psychiatric morbidity in the South-East Asian-born. They also
      indicate a need for further exploration of the unexpectedly high levels of
      psychiatric morbidity among some ethnic elderly groups, specifically the Dutch-
      and Italian-born. The findings demonstrate the persistence of high rates of
      presentation for psychotic disorders among Eastern European-born populations,
      many years post migration.

PMID- 9272264
TI  - Comparative levels of psychological distress in a pre-migratory refugee
      population.
AB  - OBJECTIVE: This study compares levels of psychological distress in a pre
      migratory sample of Vietnamese Amerasians with those in a like-aged, non
      migratory sample of Vietnamese living in Ho Chi Minh City, Vietnam. METHOD:
      Subjects were assessed using two measures developed and validated for Vietnamese
      clinical populations in the United States: the Hopkins Symptom Checklist-25 and
      the Vietnamese Depression Scale. RESULTS: Amerasians had significantly higher
      symptom levels on the depression scale of the Hopkins Symptom Checklist-25, but
      not on the other measures utilised. CONCLUSIONS: Amerasians' higher levels of
      depressive symptoms are probably a result of their traumatic lives in Vietnam,
      but may also reflect acute situational factors or selection bias.

PMID- 9272265
TI  - A prospective study of psychological distress related to refugee camp experience.
AB  - OBJECTIVE: Previous reports have suggested a direct relationship between refugee
      camp experience and levels of psychological distress among refugees.
      Specifically, it has been postulated that refugee camps with harsh conditions and
      low levels of social support foster high levels of psychological distress. The
      present study was designed to assess the relationship between camp conditions and
      social support within a refugee camp and refugees' levels of psychological
      distress. Unlike previous reports, which were based on retrospective data, the
      present study evaluated psychological distress among a group of Vietnamese
      refugees both prior to departure from Vietnam and during their refugee camp
      experience. METHOD: A group of 101 Vietnamese Amerasians was assessed at a
      transit centre in Vietnam and subsequently at a refugee camp in the Philippines.
      Assessment instruments were the Hopkins Symptom Checklist-25 and a Camp
      Comparison Questionnaire. RESULTS: There were significant decreases in symptom
      levels of anxiety and depression between the transit centre in Vietnam and the
      refugee camp in the Philippines. However, these changes were not related to
      changes in refugee camp conditions or social support within the camp.
      CONCLUSIONS: Contrary to previous reports, levels of psychological distress among
      this group of Vietnamese refugees were not related to either refugee camp
      conditions or levels of social support within the camp.

PMID- 9272266
TI  - Patterns of symptomatology and patterns of torture and trauma experiences in
      resettled refugees.
AB  - OBJECTIVES: The purpose of this study was: (i) to examine the incidence of
      psychological and medical symptomatology, torture and related trauma in a sample
      of 191 refugee clients of the Service for the Treatment and Rehabilitation of
      Torture and Trauma Survivors (STARTTS) in New South Wales (NSW), Australia; and
      (ii) to identify patterns of current symptoms, patterns of torture and trauma
      experiences and the relationships between symptoms and experiences. METHOD:
      Analysis of STARTTS client records permitted the coding of the presence/absence
      of 41 medical and psychological symptoms and of 33 torture and trauma
      experiences. Principal components analyses were used to identify patterns of
      current symptoms and patterns of torture and trauma experiences. Multiple
      regression analysis was used to identify relationships between current symptoms
      and traumatic events in the country of origin or en route to Australia. RESULTS:
      Six factors were extracted for both the symptoms and trauma experiences; the
      first symptom factor was labelled 'core posttraumatic stress disorder (PTSD)'.
      Regression analysis showed that threats and humiliation, and being forced to
      watch others being tortured best predicted scores on this factor. CONCLUSIONS:
      Although core PTSD is the dominant factor in symptomatology, comorbidity is high,
      with another three symptom factors emerging as meaningful. However, client
      reports of threats and humiliation or forced viewing of others being tortured
      should alert clinicians to the likely development of core PTSD, if it has not
      already occurred. Other implications of these findings for treatment and service
      development are discussed.

PMID- 9272267
TI  - HIV risk behaviour and HIV testing of psychiatric patients in Melbourne.
AB  - OBJECTIVES: Patients with chronic mental illnesses constitute an important risk
      group for HIV infection overseas. This study aimed to determine the prevalence of
      risk behaviours associated with HIV transmission and factors associated with HIV
      testing in psychiatric patients in Melbourne. METHODS: Inpatients and outpatients
      completed an interviewer-administered questionnaire which covered demographics,
      psychiatric diagnosis, risk behaviour, and HIV education and testing. RESULTS: Of
      145 participants, 60% were male and 55.2% had schizophrenia. Injecting drug use
      (IDU) was reported by 15.9%, a figure approximately 10 times that found in other
      population surveys. Most patients reported sex in the last decade and over 20%
      had multiple sexual partners in the last year. Of males, 12.6% reported sex with
      another male (9.2% anal sex); 19.0% of females reported sex with a bisexual male.
      Nearly half of the males reported sex with a prostitute, 2.5 times that in a
      population sample. Only 15.9% reported ever having someone talk to them
      specifically about HIV and its transmission, although one-third had been tested
      for HIV. In multivariate analysis, male-male sex, paying for sex, and IDU were
      associated with HIV testing, but those whose primary language was not English
      were less likely to be tested. Those who had received HIV education were more
      likely to have used a condom last time they had sex (OR 4.52, 95%CI 1.49-14.0).
      CONCLUSIONS: This study provides evidence that those with serious mental illness
      in Victoria have higher rates of participation in risk behaviour for HIV
      infection than those in the general community. Attention to HIV education and
      prevention in this group has been inappropriately scant; strategies to encourage
      safer behaviour are urgently needed.

PMID- 9272269
TI  - Smooth pursuit eye movements in schizophrenia in New Zealand.
AB  - OBJECTIVE: The objective of this study was to answer the following questions:
      what is the frequency of smooth pursuit dysfunction in schizophrenia in New
      Zealand; is it comparable to that observed in other populations; is it specific
      to schizophrenia; and is it represented in major ethnic groups present in New
      Zealand? METHOD: Patients with schizophrenia (n = 26) were recruited at five
      clinical facilities in the Auckland region. Diagnoses were taken from clinical
      records. Patients' smooth pursuit eye movements while following sinusoidal and
      triangular wave targets were recorded and their performance compared to a control
      population (n = 34). Eye movements were scored using the In(s/n), pursuit gain,
      and saccadic frequency measures. RESULTS: Patients with schizophrenia scored
      significantly worse than controls using the in(s/n) measure and had significantly
      higher saccadic frequencies for both targets. Percentile equivalents allow the
      estimation that about 50% of patients with schizophrenia have smooth pursuit
      dysfunction (SPD). There was no difference between groups for pursuit gain score,
      although low gain pursuit was significantly correlated with higher medication in
      the schizophrenia patient group. There were no differences associated with age,
      sex or ethnicity. The SPD marker was found in European- and Polynesian-derived
      New Zealanders. CONCLUSIONS: The results of the present study are consistent with
      results of previous studies performed elsewhere. Differences are at least partly
      ascribable to variations in methods. Smooth pursuit dysfunction is a robust
      marker for schizophrenia. Its application would be particularly useful in the New
      Zealand context as part of a first admission study looking at the effects of
      ethnicity on schizophrenia prognosis and on the stability of psychiatric
      diagnoses.

PMID- 9272268
TI  - Substance use disorders among men in prison: a New Zealand study.
AB  - OBJECTIVE: This study set out to determine the extent of alcohol and drug
      disorder among male prisoners prior to their incarceration in a New Zealand
      prison. METHOD: Sections of the Diagnostic Interview Schedule that assess alcohol
      and drug disorders according to DSM-III criteria were administered to 100
      sequential new arrivals at a male medium/minimum security prison. RESULTS: Eighty
      one percent of the prisoners had a lifetime alcohol disorder, and 39% of them had
      symptoms in the 6 months prior to incarceration. Half of the prisoners had met
      criteria for an alcohol-dependence syndrome. Thirty percent had a lifetime drug
      use disorder with 14% showing symptoms in the last 6 months prior to
      incarceration. One-quarter had been drug dependent. After adjustment of the
      lifetime prevalence estimates for the differing age distribution within the
      prison, alcohol disorder was more than twice as common among prisoners as in the
      general population, and drug use disorder was eight times as common. CONCLUSIONS:
      Since high rates of alcohol and drug disorder are found among sentenced
      prisoners, both in the 6 months prior to incarceration and over their lifetime,
      resources within the prison may need to be directed towards minimising the harm
      from substance use disorder and associated risk behaviour.

PMID- 9272270
TI  - Survivor guilt and chronic illness.
AB  - OBJECTIVE: To examine the grief reactions that may result in patients after a
      death occurs within a treatment setting for chronic illness, and in particular to
      look at the applicability of the concept of survivor guilt in these situations.
      CLINICAL PICTURE: Two patients with endstage renal disease are described. Both
      presented states of pathological grief for fellow patients. Vulnerability existed
      in both patients in terms of previous unresolved mourning and in terms of strong
      feelings of comradship with the dead patients. Both demonstrated features
      reminiscent of what has been termed the 'survivor syndrome'. TREATMENT: The
      treatment involved supportive psychotherapy allowing exploration of grief and its
      relationship to current psychosomatic crises. OUTCOME: Supportive psychotherapy
      successfully aided the resolution in one patient and made some difference in the
      other. CONCLUSION: The impact of death within a treatment unit is emphasised.
      Surviving patients may have significant distress relating to such bereavement and
      may need appropriate intervention.

PMID- 9272271
TI  - 'The bowerbird symptom': a case of severe hoarding of possessions.
AB  - OBJECTIVE: To describe a severe case of hoarding of possessions in a patient with
      obsessive-compulsive disorder. CLINICAL PICTURE: A 22-year-old male presented
      with a history from early childhood of persistent collecting of valueless objects
      and the inability to give up possessions. He had significant insight but
      ambivalent feelings about changing his behaviour, despite the degree of
      disruption it produced in his environment. TREATMENT AND OUTCOME: Attempts to
      engage the patient in treatment were unsuccessful because of the patient's
      ambivalence towards change. CONCLUSIONS: The symptom of hoarding behaviour may be
      a severe and disruptive expression of psychiatric distress, and in obsessive
      compulsive disorder it is likely to indicate a poor prognosis due to the
      difficulties of engaging the patient in treatment.

PMID- 9272272
TI  - Interaction of serotonin re-uptake inhibitors with perhexiline.
AB  - OBJECTIVE: To report two cases of perhexiline toxicity associated with selective
      serotonin re-uptake inhibitor (SSRI) treatment. CLINICAL PICTURE: Serum
      perhexiline concentrations progressively increased after a 69-year-old man was
      concurrently prescribed paroxetine for the treatment of depression. An 84-year
      old woman was admitted to hospital with severe, symptomatic perhexiline toxicity
      associated with fluoxetine treatment. TREATMENT: In both cases, perhexiline
      therapy was suspended and treatment with SSRIs was withdrawn. OUTCOME: Serum
      perhexiline concentrations declined following the withdrawal of paroxetine in one
      case, but in the case of the second patient perhexiline concentrations were
      extremely slow to decrease, resulting in referral to a rehabilitative care unit
      for convalescence. CONCLUSIONS: Serum perhexiline concentrations may be elevated
      during concurrent treatment with SSRIs, potentially resulting in severe toxicity.

PMID- 9272273
TI  - Religion and psychiatry.

PMID- 9272274
TI  - Religion and psychiatry.

PMID- 9272275
TI  - Spirituality and psychiatry.

PMID- 9272276
TI  - Rooming in: the Vellore experience.

PMID- 9272277
TI  - Firearms and New Zealand suicide.

PMID- 9272278
TI  - Treatment with GAD65 or BSA does not protect against diabetes in BB rats.
AB  - The M(r) 65,000 isoform of glutamic acid decarboxylase (GAD65) has been
      implicated as the initiating islet cell antigen in the pathogenesis of diabetes,
      primarily based on studies in non-obese diabetic (NOD) mice. To test the role of
      this islet cell autoantigen in the pathogenesis of spontaneously occurring
      diabetes in another animal model, purified recombinant human islet GAD65 was
      injected i.v. at 200 micrograms/animal into 18-day-old diabetes-prone BB rats.
      For controls, bovine serum albumin (BSA), which has also been implicated in the
      pathogenesis of diabetes, or buffer alone was injected into age matched BB rats.
      At 210 days of age there were no differences in diabetes incidence in the 3
      groups, i.e. 73% (11 of 15) in the GAD65-treated, 81% (13 of 16) in the BSA
      treated and 65% (11 of 17) in the buffer-treated animals, or in the median age at
      onset of disease, i.e. 79 days (range 65-111), 87 days (range 60-107) and 86 days
      (range 74-109), respectively. The lack of protection against diabetes following
      GAD65 treatment could hypothetically be explained by no or by an aberrant
      expression of GAD in BB-rat islet cells. However, immunohistochemistry of
      pancreata and immunoblotting analysis of isolated islets showed that the
      expression of GAD65 and GAD67 was similar in BB and Lewis rats. In conclusion,
      these data indicate that neither GAD65 nor BSA autoimmunity is important for the
      development of diabetes in BB rats, in contrast to the situation in NOD mice, and
      further emphasizes that extrapolation from only one animal model to autoimmune
      diabetes in general may not be appropriate.

PMID- 9272279
TI  - Serum complement activation of SLE patients during plasmapheresis.
AB  - The erythrocyte complement receptor 1 (ECR1)-immune complex binding assay is a
      sensitive method for the determination of complement fragments which can be
      activated by bovine serum albumin (BSA)-anti-BSA in vitro. When the C3b/C4b
      containing bovine serum albumin (BSA)-anti-BSA was formed in the presence of the
      serum of patients with systemic lupus erythematosus (SLE) its binding to ECR1 was
      found to be lower than that formed in sera of normal volunteers. The
      plasmapheresis of SLE patients homozygous for the CR1/E high density allele
      displays a beneficial effect on the formation of C3b/C4b containing BSA-anti-BSA
      and its binding to ECR1. There was no significant correlation between the serum
      C3/C4 level and the percentage of C3b/C4b containing BSA-anti-BSA binding to the
      ECR1 of SLE patients during plasmapheresis. At the same time, there was an
      inverse correlation between the serum immune complex level and the ECR1 binding,
      which was significant in 3 of 5 cases. These data suggest that, besides the
      determination of different components of complement activation, the functional
      assay of complement activation might be useful in monitoring the effect of
      plasmapheresis in SLE.

PMID- 9272280
TI  - Fetal exposure to interferon-gamma leads to induction of antigen-presenting
      molecules and leukocyte recruitment.
AB  - Embryonic tissue expresses a very low level of MHC molecules, and these few
      appear only late in ontogeny. Possibly related are deficiencies in the expression
      of TAP molecules and also the fetus' need to avoid maternal immunologic
      rejection. However, the fetus may overcome the lack of Ag-presenting molecules
      when threatened by inflammation from pathogens that cross the placental barrier.
      To study embryonic responses to inflammation, we used transgenic mice that
      express pancreatic IFN-gamma (Ins-IFN-gamma mice). In this unique model, the
      transgene is expressed well before birth, permitting evaluation of MHC class I,
      II and TAP-1, -2 expression as well as immunohistological characteristics of
      pancreatic inflammation. Our results revealed strong positivity for MHC class I
      and II molecules in the pancreata of Ins-IFN-gamma mice beginning at embryonic
      day (E) 12, but not in those of nontransgenic embryos. TAP-1 and -2 were also
      evident in transgenic pancreatic tissue beginning at E10 simultaneously with
      formation of the pancreatic primordium. Interestingly, as early as E14, the
      transgenic pancreata contained CD4- CD8- T lymphocytes and other bone marrow
      derived cells such as monocytes. These results suggest that embryos respond to
      immunological stimuli by producing Ag-presenting molecules and recruiting
      immature T cells and monocytes.

PMID- 9272281
TI  - Is premature ovarian failure an autoimmune disease?

PMID- 9272282
TI  - Expression of the gastric H/K-ATPase alpha-subunit in the thymus may explain the
      dominant role of the beta-subunit in the pathogenesis of autoimmune gastritis.
AB  - The two subunits of the gastric H/K ATPase, namely the catalytic alpha-subunit
      and the glycoprotein beta-subunit, are the major targets of parietal cell
      autoantibodies associated with human and murine autoimmune gastritis. The murine
      disease induced by neonatal thymectomy is T cell-mediated. We have previously
      shown that transgenic expression of the H/K ATPase beta-subunit gene in the
      thymus prevented the development of autoimmune gastritis induced by thymectomy.
      However, little is known of the contribution of the H/K ATPase alpha-subunit in
      disease development. Here, we show that (1) in contrast to the gastric H/K ATPase
      beta-subunit, the alpha-subunit gene is expressed in normal BALB/c thymus. (2)
      transgenic expression of the gastric H/K ATPase alpha-subunit gene in the thymus
      failed to prevent the development of autoimmune gastritis and (3) normal BALB/c
      and transgenic mice expressing the alpha-subunit in the thymus develop autoimmune
      gastritis following immunisation with purified murine gastric H/K ATPase, whereas
      transgenic mice expressing the beta-subunit in the thymus do not. We propose that
      the expression of the H/K ATPase alpha-subunit in the normal thymus may account
      for the predominant role of the beta-subunit in the development of autoimmune
      gastritis induced either by thymectomy or by immunisation with the ATPase.

PMID- 9272283
TI  - Immunogenetics and the cause of autoimmune disease.
AB  - Autoimmune disease results from the action of environmental factors on a
      predisposed genotype. In this review, the role of genetic susceptibility in the
      aetiology of autoimmune disease is examined. As the genetics of autoimmune
      diabetes has been studied more intensively than that of other autoimmune
      diseases, supporting evidence is drawn principally from that example. Autoimmune
      diseases are not inherited as entities but as constitutions which confer an
      increased probability of developing disease. It is proposed that there are two
      components to autoimmune disease susceptibility. One confers susceptibility to
      autoimmunity per se, while the other determines tissue specificity. In this
      review, the concept of liability is introduced as a tool used in quantitative
      genetics and is applied to the analysis of autoimmune diabetes by considering a
      threshold model. In this example, empirically derived incidence figures are used
      to calculate heritability which is a relative measure of the influence of
      genetics and environmental factors. The validity of applying the concept of
      liability to diabetes is confirmed by examining the values of heritability
      calculated from empirical data obtained from different kindred relationships, and
      by confirming that the assumptions on which liability is based are supported by
      recent gene mapping data. Finally, the physiological significance of liability is
      considered and its significance to the cause of autoimmunity discussed.

PMID- 9272284
TI  - Abscess formation in posterior fossa dermoid cysts.

PMID- 9272285
TI  - Congenital lumbosacral lipomas.
AB  - Congenital lumbosacral lipomas can be responsible for progressive defects. The
      general feeling is that tethering of roots, filum, or cord probably explains this
      evolution, and that untethering of these structures could prevent late
      deterioration. Like the vast majority of neurosurgeons, we too have routinely and
      systematically operated on lumbosacral lipomas, even in the absence of
      neurological deficits. This policy stemmed from our belief that spontaneous
      neurological deterioration was frequent, recovery from preoperative deficits
      rare, and surgery both efficient and benign in nature. After 22 years of
      experience, we felt that it was necessary to review our series of 291 lipomas (38
      lipomas of the filum and 253 of the conus) operated on from 1972 to 1994. To
      reassess the value of prophylactic surgery, we attempted an accurate evaluation
      of (1) the risk of pathology, (2) the risks involved in surgery, (3) the
      postoperative outcome with respect to preoperative deficits, and (4) the
      postoperative outcome in asymptomatic patients at 1 year and at maximum follow
      up. Special attention was paid to 93 patients whose postoperative follow-up was
      more than 5 years (average 8.7, median 8, range 5-23 years). Of these 93
      patients, 39 were asymptomatic preoperatively (7 with lipoma of the filum and 32
      with lipoma of the conus). Lipomas of the filum and of the conus are entirely
      different lesions and were studied separately. In 6 cases prenatal diagnosis had
      been possible. The mean age at surgery was 6.4 years. Low back skin stigmata were
      present in 89.4% of cases. Preoperative neurological deficits existed in 57% of
      the patients and were congenital in 22%. Clinical signs and symptoms recorded
      were pain in 13.3% of the patients and/or neurological deficits affecting
      sphincter (52%), motor (27.6%) and sensory (22.4%) functions. Deficits were
      progressive in 22.4% of cases, slowly progressive in 58.8% of these and rapidly
      progressive in the remaining 41.2%. In 36 patients (13.2%) the lipomas were seen
      to grow either subcutaneously or intraspinally. Among these patients, 21 were
      infants, 2 were obese adolescents, and 10 were pregnant women. The metabolism of
      the fat within the lipomas was studied in 11 patients and found to be similar to
      that at other sites. Lipomas were associated with various other malformations,
      either intra- or extraspinal. These associated anomalies were rare in the case of
      lipomatous filum (5.2%) but frequent with lipomas of the conus, except for
      intracranial malformations (3.6%). Therapeutic objectives were spinal cord
      untethering and decompression, sparing of functional neural tissue and prevention
      of retethering. Procedures used to achieve these goals were subtotal removal of
      the lipoma, intraoperative monitoring, duroplasty, and sometimes closure of the
      placode. Histologically, lipomas consisted of normal mature fat. However, 77% of
      them also included a wide variety of other tissues, originating from ectoderm,
      mesoderm, or entoderm. This indicates that lipomas are either simple or complex
      teratomas. The results of the study are as follows. (1) Surgery was easy and safe
      when performed for treatment of lipomas of the filum (no complications), but
      difficult and hazardous in the case of lipomas of the conus (20% local, 3.9%
      neurological complications). (2) All types of deficit could be improved by
      surgery, which was beneficial in all cases of lipoma of the filum and 50% of
      cases of lipoma of the conus. (3) In asymptomatic patients long-term surgical
      results depended on the anatomical type of the lipoma. They were excellent in
      lipomas of the filum. In lipomas of the conus they were good in the short term
      but eroded with time. At more than 5 years of follow-up only 53.1% of the
      patients were still free of symptoms. (4) Reoperations were performed in 16
      patients (5.5%), 5 (31.2%) of whom improved postoperatively, while in 7 (43.7%)
      progression stopped, in 3 (18.7%) deterioration continued and in 1 (6.2%) the
      condition was wor

PMID- 9272286
TI  - Embryogenesis. Why do we need a new explanation for the emergence of spina bifida
      with lipoma?
AB  - Spina bifida with lipoma is a human malformation that most often affects the
      lumbosacral area. It is a complex morphological type. Its origin is
      controversial, and none of the previous hypotheses can be retained in view of the
      most recent advances in experimental embryogenesis. Contrary to earlier opinions,
      adipocytes cannot arise from meninges, vessels or glial cells and spina bifida
      cannot be explained by incarceration of mesodermal tissues during primary
      neurulation or developmental defect at the level of the tail bud. Spina bifida
      with lipoma, which actually involves all the derivatives of the so-called dorsal
      mesoderm, must therefore result from abnormal development of this mesoderm, which
      is induced by the dorsal neural tube. The location of the primary defect (dorsal
      mesoderm or neural tube) remains to be established.

PMID- 9272287
TI  - Malignant supratentorial astrocytomas of late childhood. Our experience with 25
      cases.
AB  - The authors present 25 patients ranging in age from 8 to 16 years who had
      malignant supratentorial astrocytomas. This type of lesion represents one of the
      most important and statistically significant causes of morbidity and mortality in
      late childhood. Compared to adult malignant supratentorial astrocytomas, these
      lesions seem to show a better survival rate. The reason is unknown. The authors
      present their experience regarding the importance of radical removal and
      histology for a better prognosis.

PMID- 9272288
TI  - Hydrocephalus and chronically increased intracranial pressure in achondroplasia.
AB  - Two achondroplastic children with ventriculomegaly are reported. The patients had
      no signs of increased intracranial pressure, but in one blindness had previously
      been detected by the parents. Neuroradiological examinations showed
      ventriculomegaly in both. Intracranial pressure remained at high levels (20-55
      mmHg) preoperatively; ventriculo-peritoneal shunting was performed in both cases,
      and postoperatively levels fell to normal (5-16 mmHg). The need for the treatment
      of ventriculomegaly seen in achondroplastic children is analyzed on the basis of
      these two patients, with a brief review of literature.

PMID- 9272289
TI  - Long-term follow up of a growing skull fracture treated by dura and cranioplasty
      with artificial dura mater and methylmethacrylate.
AB  - We report the long-term follow up of a growing skull fracture treated by
      duraplasty and cranioplasty with artificial dura mater and methylmethacrylate.
      The patient had undergone duraplasty and cranioplasty 19 years earlier at the age
      of 1 year and 11 months old. We examined the growth of the skull and the long
      term adaptation between his own skull and methylmethacrylate 19 years after
      cranioplasty.

PMID- 9272290
TI  - Dissociation of 99mTc-ECD and 99mTc-HMPAO distributions in herpes simplex
      encephalitis.
AB  - In herpes simplex encephalitis (HSE), the authors noted an evident dissociation
      between the 99mTc-ethyl cysteinate dimer (ECD) and 99mTc-d,l-hexamethyl-propylene
      amine oxime (HMPAO) single photon emission computed tomographies (SPECTs). The
      patient was a 5-year-old boy with diffuse type of pontine glioma, which was
      treated with hyperfractionated radiotherapy. Two weeks after the completion of
      radiation therapy, a lesion suggesting that of HSE was noted in the right fronto
      temporal region on magnetic resonance images. 99mTc-HMPAO SPECT showed an
      increased accumulation of the tracer in this lesion. On the 99mTc-ECD dynamic
      SPECT, an exaggerated accumulation of the tracer was noted within 80 s of
      administration, followed by a rapid drop in the accumulation, resulting in a low
      accumulation in 10 min. It was assumed that this dissociation was due to the
      different mechanisms to trap HMPAO and ECD in the brain tissue.

PMID- 9272291
TI  - How to manage patients on long-term oral corticosteroids: recommendations from
      available guidelines.

PMID- 9272293
TI  - A longitudinal study of lung impairment in patients with primary Sjogren's
      syndrome.
AB  - OBJECTIVE: A longitudinal evaluation of lung involvement in primary Sjogren's
      syndrome (SS). METHODS: Eighteen non-smoking women fulfilling the European
      criteria for primary SS were followed for 55 months (range 26-137 mos.). These
      were consecutive patients with exclusion for current smokers and patients with
      lung diseases. Every patient underwent clinical examination, chest radiographs
      and lung function tests (spirography, flow/volume loop and CO lung diffusing
      capacity measurements). No patient was given any immunosuppressive or mucolytic
      therapy. RESULTS: Cough, dyspnea on exertion and recurrent bronchitis were
      observed in 50, 40 and 20% of the patients respectively and their frequency did
      not change with time. Chest radiographs were and remained normal. At
      presentation, lung volumes and diffusing capacity were in the normal range,
      whereas expiratory flows in the small airways tended to be in the low range. With
      time, the peak expiratory flow (PEF) significantly increased (95.8 +/- 4.6 v
      103.5 +/- 4.6, mean +/- SE, % of predicted, Wilcoxon, p < 0.05) whereas the lung
      transfer factor for CO (TLCO) and the transfer coefficient (KCO = TLCO/alveolar
      volume) decreased (92.9 +/- 4.0 v 87.0 +/- 4.0 and 89.7 +/- 2.4 v 84.2 +/- 2.6
      respectively, p < 0.05 for both). The TLCO decrease, corrected for the duration
      of follow-up, correlated with the titers of IgA circulating immune complexes
      (CIC) at presentation and to a lesser extent with the occurrence of cough.
      CONCLUSION: During the follow-up of these primary SS patients, respiratory
      symptoms did not change, the recurrent respiratory infection rate was low, and no
      cases of pulmonary hypertension or lymphoma was observed. The diffusion capacity
      decrease was associated with IgA CIC titers at presentation. This impairment
      could contribute to dyspnea during its evolution over a lifetime but is too
      slight to explain the dyspnea on exertion seen in most of our patients.

PMID- 9272292
TI  - Effect of treatment with methotrexate, hydroxychloroquine, and prednisone on
      lymphocyte polyamine levels in rheumatoid arthritis: correlation with the
      clinical response and rheumatoid factor synthesis.
AB  - OBJECTIVE: Polyamines are increased in activated lymphocytes, including
      peripheral blood lymphocytes (PBL) from patients with rheumatoid arthritis (RA),
      and are important in modulating immune-mediated cellular responses. In vitro
      studies have suggested that methotrexate (MTX) interferes with polyamine
      synthesis. This study evaluated the in vivo polyamine response to MTX compared to
      other anti-arthritic agents, and correlated it with the clinical and
      immunological response. METHODS: The polyamine content of PBL was determined in
      14 RA patients at initiation of treatment with MTX (n = 8), hydroxychloroquine
      (HCQ) (n = 3), or prednisone (n = 3), and then monthly for four months. IgM
      rheumatoid factor (RF) synthesis by PBL in vitro was assessed and tender joints
      were counted monthly. RESULTS: Polyamines (spermine and spermidine) decreased by
      55% at three months in the MTX group compared to 4% and 9% in the HCQ and
      prednisone groups, respectively (p < 0.01). However, group differences in the
      clinical and immunological response were not significant. In the MTX group there
      was a positive correlation between polyamine levels and the joint count. Such a
      correlation was not observed in the other groups. CONCLUSION: These data suggest
      that MTX interference with the polyamine pathway is not shared by prednisone and
      HCQ, and is associated with its beneficial effect in RA.

PMID- 9272294
TI  - Quality of life of patients with familial Mediterranean fever.
AB  - OBJECTIVE: The aim of the present study was to assess the quality of life (QOL)
      of patients with Familial Mediterranean Fever (FMF) and to explore its possible
      contributing factors. METHODS: One hundred and two FMF patients were evaluated
      using a QOL Scale, and were compared to 124 healthy controls. The QOL scale
      includes 16 items, each measured on a 7-point scale (7 indicating maximal
      satisfaction). RESULTS: The total QOL score of FMF patients was significantly
      lower than that of the controls: 81.6 +/- 19.2 vs 88.0 +/- 12.8 (p < 0.01). Male
      and female patients reported similar QOL scores. QOL was inversely correlated
      with the number of FMF attacks in the last year (r = -0.302, p = 0.002), and with
      the number of FMF hospitalizations (r = -0.238, p = 0.017). Patients with
      widespread pain, sleep disturbances and headaches had significantly lower QOL
      scores than patients without them. CONCLUSIONS: The QOL of FMF patients was found
      to be impaired compared to healthy controls. Further studies are needed to
      determine the exact factors affecting the quality of life of FMF patients.

PMID- 9272295
TI  - Antiphospholipid antibodies in primary Sjogren's syndrome: prevalence and
      clinical significance in a series of 80 patients.
AB  - OBJECTIVE: To determine the prevalence and clinical significance of
      antiphospholipid antibodies (aPL) in a cohort of patients with primary Sjogren's
      syndrome (SS). METHODS: Eighty patients with primary SS were studied
      prospectively. The prevalence of aPL and characteristics of the clinical and
      laboratory features of these patients were compared with those of the following
      groups of patients: (i) 50 patients with SS associated with systemic lupus
      erythematosus (SLE); (ii) 100 patients with SLE without SS; and (iii) 100 healthy
      blood donors from the blood bank of our hospital. RESULTS: Only 11 (14%) patients
      with primary SS were found to have aPL (anticardiolipin antibodies or lupus
      anticoagulant, or both) in their sera, but anti beta 2-glycoprotein I antibodies
      were not detected in any patient. In contrast, aPL were detected in 12 (24%)
      patients with SS secondary to SLE and in 21 (21%) patients with SLE without SS.
      None of the healthy controls presented aPL in their sera. Patients with primary
      SS presented a lower prevalence of thrombocytopenia (p < 0.05) and livedo
      reticularis (p < 0.01) compared with the other two groups of patients. No patient
      with primary SS was diagnosed as having an antiphospholipid syndrome (APS), while
      4 (8%) patients with secondary SS and 9 (9%) with SLE without SS were found to
      have APS (p < 0.05). CONCLUSION: In patients with primary SS, aPL are present in
      a lower percentage than in patients with SS secondary to SLE or in patients with
      SLE without SS. The presence of aPL in these primary SS patients is not
      associated with the clinical events of APS.

PMID- 9272296
TI  - Erosive azotemic osteoarthropathy of the hands in chronic ambulatory peritoneal
      dialysis and hemodialysis.
AB  - OBJECTIVE: We studied the prevalence and significance of erosive azotemic
      osteoarthropathy (EAO) and its relationship with other osteoarticular
      abnormalities of dialysis-associated arthropathy (DAA). METHODS: 112 patients
      undergoing maintenance dialysis were studied: 63 hemodialysis (HD) and 49
      continuous ambulatory peritoneal dialysis (CAPD). X-ray of the hands, shoulders,
      pelvis and cervical spine were examined for destructive spondyloarthropathy
      (SDA), bone cysts (BC), EAO and subperiosteal resorption. Beta 2-microglobulin
      (beta 2-m) and PTH were also measured. RESULTS: Fifteen patients (13%) had EAO,
      usually in several joints of the hands, DIPs being the most frequently affected.
      Both patients on HD and those on CAPD had EAO, although the prevalence was higher
      in the HD group, 12 (19%) vs. 3 (6%). Patients with EAO were older (p < 0.05) and
      had more carpal tunnel syndrome (CTS) (p < 0.05) and BC (p < 0.01). Only 3 out of
      15 patients with EAO had severe secondary hyperparathyroidism (sHPTH) (PTH >
      500), while 9/15 had neither radiologic nor laboratory evidence of sHPTH. No
      differences were found regarding the duration of dialysis, or beta 2-m or PTH
      level. CONCLUSION: EAO is not related to sHPTH and should be included within the
      spectrum of the clinical manifestations of DAA. Due to its location and
      radiologic picture, it is possible that etiologic factors leading to primary
      osteoarthritis may play a role in the development and evolution of EAO.

PMID- 9272298
TI  - Effects of five-day versus one-day infusion of iloprost on the peripheral
      microcirculation in patients with systemic sclerosis.
AB  - OBJECTIVE: To evaluate the effects of iloprost infusion on the microcirculation
      in patients suffering from severe Raynaud's phenomenon secondary to systemic
      sclerosis. METHODS: Eight patients received a 7-hour infusion of iloprost for
      five consecutive days and then for one day 3 months later. The effects on
      vascular distensibility were evaluated by piezoelectric plethysmography before
      and after the treatment and at 2, 4 and 6 weeks. RESULTS: The beneficial effects
      on the peripheral microcirculation were statistically significant after five days
      of infusion (distensibility index: 0.18 +/- 0.01 vs 0.23 +/- 0.01, p < 0.002) and
      lasted for less than four weeks, whereas no difference (0.22 +/- 0.04 vs 0.24 +/-
      0.02, p: ns) was seen after one day of treatment. One patient suffered from
      typical angina pectoris with electrocardiographic changes of the ST wave detected
      during the infusion. CONCLUSION: Our results show that a five-day infusion of
      iloprost has an effect which lasts from two to four weeks; after four weeks the
      distensibility index returned to the baseline value. The one-day infusion had no
      effect on the vascular bed, studied by the piezoelectric pletysmographic method.
      Treatment with five consecutive days of infusion every four weeks is an
      impracticable scheme to adopt, however. We have therefore instituted a treatment
      schedule of a single daily infusion every four weeks with the aim of maintaining
      the effects induced by the initial five-day infusion. The preliminary results
      obtained with this schedule are reported.

PMID- 9272297
TI  - Clinical, laboratory and immunogenetic aspects of arthritis associated with
      chronic lymphocytic thyroiditis.
AB  - OBJECTIVE: Synovial fluid effusions and/or arthritis may be found in patients
      with chronic lymphocytic thyroiditis (CLT), even in the absence of
      hypothyroidism. Sometimes these arthropathies can be attributed to the rheumatic
      diseases frequently associated with CLT, but in some instances the arthritis
      seems to be independent of any of the diseases known to cause arthritis, and
      therefore remains unclassified. This study was carried out in an attempt to
      characterize the type and outcome of arthritis associated with CLT. METHODS: We
      performed a prospective study with a follow-up of 6.42 years (range 4-13) on 33
      patients affected with CLT and presenting with arthritis. All conditions known to
      cause arthritis were previously excluded. Investigations included HLA typing, x
      ray of the affected joints and, when possible, synovial fluid (SF) analysis with
      an interleukin (IL)-1 beta determination. Patients were divided based on their
      clinical presentation into two groups: those with polyarthritis and those with
      oligoarthritis. RESULTS: During the follow-up, 8 out of 16 patients with
      polyarthritis developed severe rheumatoid arthritis, characterized by bone
      erosions, high levels of SF IL-1 beta and an increased frequency of HLA DR4. The
      other 8 patients had polyarthritis in a mild, non-erosive form, which responded
      well to symptomatic drugs. Oligoarthritis, found in 17 patients, also showed a
      mild evolution, with frequent spontaneous remissions. The non-rheumatoid
      polyarthritis and oligoarthritis patients were characterised by the absence of
      bone erosions, low levels of SF IL-1 beta and an increased frequency of HLA DR3.
      CONCLUSIONS: We conclude that it is possible to find in association with CLT a
      type of inflammatory arthritis characterized by a mild, non-erosive evolution,
      low SF levels of IL-1 beta and an increased frequency of HLA-DR3. This arthritis
      seems to be independent of thyroid dysfunction and shows a clinical pattern
      similar to the arthritis usually found in connective tissue diseases.

PMID- 9272299
TI  - The association of dehydroepiandrosterone sulphate levels with bone mineral
      density in systemic lupus erythematosus.
AB  - OBJECTIVES: To evaluate, in premenopausal systemic lupus erythematosus (SLE)
      patients, the possible protective role of androgens on bone mass. METHODS: Bone
      mineral density (BMD) was measured in the lumbar spine and femoral neck in 37
      women with SLE (mean age 31.1 years) without disturbances or therapy that could
      interfere with bone metabolism except glucocorticoid therapy. We measured serum
      intact parathyroid hormone (iPTH): 2.5 +/- 1.3 pmol/L, serum testosterone: 1.6 +/
      1.1 nmol/L, salivary testosterone: 0.09 +/- 0.1 nmol/L, and serum
      dehydroepiandrosterone sulphate (DHEAS): 2.2 +/- 2.2 umol/L. RESULTS: BMD in the
      spine (L2-L4) was 0.94 +/- 0.1 g/cm2 and in the femoral neck 0.77 +/- 0.1 g/cm2.
      Four patients (10.8%) had osteoporosis. We found a significant positive
      relationship between DHEAS and BMD, a negative relationship between DHEAS and the
      glucocorticoid dose at the time of study, and a negative correlation between iPTH
      and DHEAS. CONCLUSIONS: Bone loss in corticosteroid-treated premenopausal
      patients with SLE may be modulated through down-regulation of the endogenous
      production of DHEAS.

PMID- 9272300
TI  - Two NSAIDs, nimesulide and naproxen, can reduce the synthesis of urokinase and IL
      6 while increasing PAI-1, in human OA synovial fibroblasts.
AB  - OBJECTIVES: To evaluate the effect of therapeutic and pharmacologic
      concentrations of two non-steroidal anti-inflammatory drugs (NSAIDs), nimesulide
      and naproxen, on the synthesis of urokinase (uPA), plasminogen activator
      inhibitor (PAI-1) and interleukin-6 (IL-6) in human synovial fibroblasts isolated
      from osteoarthritis (OA) patients. METHODS: Urokinase, PAI-1, and IL-6 production
      were measured by specific ELISA. RESULTS: Nimesulide and naproxen induced a dose
      dependent decrease in uPA synthesis. The two drugs, at therapeutic
      concentrations, exerted a stimulatory effect on the synthesis of PAI-1 whereas
      the synthesis of IL-6 was significantly reduced by both NSAIDs. CONCLUSION: The
      results of this study indicate some of the mechanisms by which nimesulide and
      naproxen could exert their effects on the arthritis process. The suppressive
      action of the two drugs on the synthesis of uPA, while stimulating PAI-1
      production, may have a positive impact on the balance of plasminogen
      activator/inhibitor, which could help reduce cartilage catabolism.

PMID- 9272301
TI  - Antibodies to streptococcal cell wall in psoriatic arthritis and cutaneous
      psoriasis.
AB  - OBJECTIVE: To evaluate the possible role of streptococcal cell wall antigens in
      the development of psoriatic arthritis. METHODS: IgM, IgA and IgG class serum
      antibodies against peptidoglycan-polysaccharide (PG-PS) and peptidoglycan (PG),
      both from group A streptococcus, were measured in patients with psoriatic
      arthritis (PA), non-arthritic psoriasis (NAP), rheumatoid arthritis (RA) and in
      healthy controls, using ELISA. RESULTS: Both groups of psoriatic patients had
      elevated IgA levels specific to streptococcal PG-PS. No association with the
      severity of the skin disease or with the different subsets of PA was detected.
      Higher concentrations of IgG against the two streptococcal preparations was
      observed in PA than in RA. Analysis of antibody levels in patients with recent
      onset arthritis showed lower concentrations of IgM antibodies against
      streptococcal as well as control antigens in early than in late PA, whereas an
      overall increase of specific IgA and IgG antibodies was observed in early RA.
      CONCLUSION: The results suggest chronic mucosal stimulation of lymphocytes by
      long-lived streptococcal antigens in patients with psoriasis, without any
      difference observed between PA and NAP. The differences between recent onset
      versus established PA and RA could reflect a distinct immunopathology in the two
      arthritides.

PMID- 9272302
TI  - Human cytomegalovirus infection and systemic lupus erythematosus.
AB  - OBJECTIVE: Viruses are considered possible aetiologic agents of autoimmune
      disease. Evidence suggests that human cytomegalovirus (HCMV) may be a
      pathogenetic factor in systemic lupus erythematosus (SLE). We undertook a
      seroepidemiological study to determine whether HCMV infection is increased in
      patients with SLE. METHODS: Sero-epidemiologic data, indicative of virus
      prevalence, were obtained by enzyme immunoassay. RESULTS: Eighty-eight of 97
      serum samples (90.7%) taken from adult patients with SLE were seropositive for
      HCMV. By contrast, HCMV was detected in only 32 of 50 (64.0%) adult patients with
      rheumatoid arthritis (RA) and 42 of 97 (43.3%) normal controls. The odds ratio
      for HCMV prevalence in SLE/normal controls was 14.53 (95% CI is 6.39 to 33.04).
      For comparison, data for herpes simplex virus-I (HSV-I) seropositivity were
      obtained from the same three groups. Seventy-eight patients with SLE (80.4%), 40
      patients with RA (80.0%) and 57 normal controls (58.8%) were seropositive for
      this closely-related herpesvirus. CONCLUSION: The data shows a specific and
      highly significant association between infection with HCMV and a clinical
      diagnosis of SLE.

PMID- 9272303
TI  - Polymyalgia rheumatica in patients with ankylosing spondylitis: a report of 5
      cases.
AB  - OBJECTIVE: To report the cases of 5 elderly male patients with ankylosing
      spondylitis (AS) who developed polymyalgia rheumatica (PMR). MATERIALS AND
      METHODS: The files of 5 patients with AS who developed PMR were retrospectively
      reviewed. The demographic, clinical, laboratory characteristics and outcome of
      these patients were summarized. RESULTS: All 5 patients were male, 65-80 years
      old at the time of their PMR diagnosis. The diagnosis of AS was made
      simultaneously based on clinical and radiological data; the age at onset of
      symptoms retrospectively attributable to AS was 20-40 years in three cases, while
      in the two other patients it could not be determined. The patients presented with
      typical symptoms of PMR and responded to steroid treatment. HLA B27 was found in
      three cases, while HLA DR did not show a consistent pattern. CONCLUSIONS: The
      coexistence of AS and PMR could be more than coincidental. Further screening of
      both patient populations is needed to assess the true extent of this preliminary
      observation.

PMID- 9272304
TI  - Development of arthritis and hypothyroidism during alpha-interferon therapy for
      chronic hepatitis C.
AB  - Alpha-interferon (alpha-IFN) therapy may induce, reveal or exacerbate various
      autoimmune-related disorders. The most common is the development of
      autoantibodies, while clinically overt autoimmune diseases are rare. We describe
      a 49-year-old woman who developed seronegative rheumatoid-like arthritis and
      autoimmune hypothyroidism after 7 months of human lymphoblastoid alpha-IFN
      therapy given for hepatitis C virus-related chronic active hepatitis (CAH-HCV).
      There was no family or personal history of autoimmune, thyroid or articular
      diseases. Our patient required continuous therapy for arthritis and
      hypothyroidism despite discontinuation of alpha-IFN. This suggests that alpha-IFN
      therapy may induce the contemporary appearance of two different persistent
      autoimmune-related diseases in the same patient. However, chronic HCV infection
      may play an important adjuvant role in the development of these diseases.

PMID- 9272305
TI  - Extradural spinal tophaceous gout: evolution with medical treatment.
AB  - A patient with chronic tophaceous gouty arthritis developed paraparesis due to
      medullar compression from a urate sodium tophus. We report the MRI features of
      this tophaceous gout, which showed an extradural hyperintense signal with an
      isointense nodule signal on T1 weighted sequences. Surgical removal of the
      epidural lesion resulted in complete clinical recovery. At the upper level of the
      spine, an extension of the epidural lesion was not removed, but after one year of
      medical treatment of the gout, MRI showed regression of the epidural compression.

PMID- 9272306
TI  - Benign familial hyperphosphatasemia: a report of two families and review of the
      literature.
AB  - Benign familial hyperphosphatasemia is a rare biochemical abnormality of
      hereditary nature, characterized by the presence of persistently elevated levels
      of serum alkaline phosphatase in several members of the same family, in the
      absence of disease or any known cause of hyperphosphatasemia. To date, there have
      been 29 pedigrees reported in the literature. Another two families affected with
      hyperphosphatasemia, originating in an increase in the bone isoenzyme, are
      described. The epidemiology, inheritance, isoenzymatic patterns, postulated
      mechanisms and clinical significance of this entity are discussed.

PMID- 9272307
TI  - Nerve growth factor and autoimmune rheumatic diseases.
AB  - Nerve growth factor (NGF) is the first discovered and best known neurotrophic
      factor and is required for the survival and differentiation of a variety of
      neuronal cell types in both the peripheral and central nervous system. Recent
      studies indicate that NGF is synthesized by cells of immune system lineage and
      that its level increases during inflammatory responses, while cytokines such as
      interleukin-1 beta and tumor necrosis factor-alpha are potent inducers of NGF
      secretion. The role played by NGF on cells of the immune system was strengthened
      by recent evidence demonstrating that cells normally present in inflammatory
      tissues, such as mast cells and lymphocytes, express NGF receptors and are
      receptive to the action of NGF. Studies carried out in our and other laboratories
      showed that NGF is expressed in the synovial fluid of patients with rheumatoid
      arthritis and other forms of chronic arthritis, as well as in the synovium of
      pharmacologically-induced arthritis in animal models. Moreover, arthritic
      transgenic mice which carry and express the human tumor necrosis factor-gene also
      showed elevated levels of NGF. Significant increases in NGF levels have been
      found in the sera of patients with systemic lupus erythematosus and in the dermis
      of patients affected by systemic sclerosis. In this paper the hypothesis that NGF
      is involved in the pathophysiology of autoimmune rheumatic arthritis is
      discussed.

PMID- 9272308
TI  - Interleukin-1 receptor antagonist in neonates, children and adults, and in
      patients with pauci- and polyarticular onset juvenile chronic arthritis.
AB  - OBJECTIVE: The production of interleukin (IL) -1 alpha IL-1 beta and IL-1
      receptor antagonist (IL-1ra) by blood mononuclear cells (MNC), as well as the
      corresponding serum levels of IL-1ra were examined in blood samples from
      umbilical cords (n = 11), children (n = 40) and adults (n = 20), and in 42
      patients with juvenile chronic arthritis (JCA) of the pauci- or polyarticular
      onset type. RESULTS: IL-1ra serum levels were found to differ significantly
      between the three age groups, being higher in neonates (569 pg/ml) than in
      children (70 pg/ml) and adults (177 pg/ml). IL-1ra production in E. coli
      lipopolysacharide (LPS) stimulated-cultures of MNC was also significantly higher
      in neonates (median 2451 pg/ml) than in children (1526 pg/ml), but similar to
      that in adults (2107 pg/ml). IL-1ra levels in the sera of both subgroups of JCA
      patients were significantly elevated (median 257 pg/ml), but did not reflect
      paraclinical or clinical disease parameters. In samples of synovial fluid the IL
      1ra levels tended to be fairly high, up to approximately 2 ng/ml, but they did
      not reflect the serum levels of IL-1ra. CONCLUSION: These findings suggests that
      the upregulation of IL-1ra production forms part of the immunoregulatory response
      in JCA patients, and that the insufficient production of IL-1ra is unlikely to
      contribute to the pathogenesis of JCA.

PMID- 9272309
TI  - Actinomycotic splenic abscesses presenting with arthritis.
AB  - An 18-month-old Caucasian female began with a high fever. She developed swelling
      in one finger and one toe. Abdominal ultrasound revealed multiple abscesses in
      her spleen. Multiple blood culture and splenic abscess aspirations grew no
      pathogens. She had transient response to multiple antibiotics and splenic abscess
      drainage, but fever returned along with subcutaneous nodules. Culture of splenic
      tissue from her second splenic drainage eventually grew one organism identified
      as Actinomyces naeslundii. Therapy with high dose penicillin followed by
      amoxicillin p.o. and total splenectomy led to complete recovery.

PMID- 9272310
TI  - Heart rate variability and cardiac autonomic function in a case of Wegener's
      granulomatosis.

PMID- 9272311
TI  - The clinical value of serum immunoglobulin levels in early rheumatoid arthritis.

PMID- 9272312
TI  - Anti-bacterial antibodies in Behcet's disease.

PMID- 9272313
TI  - Adult hypophosphatasia in an aged patient.

PMID- 9272314
TI  - A stepwise increased dose of auranofin does not influence gastrointestinal side
      effects.

PMID- 9272315
TI  - Autoantibodies--diagnostic, pathogenic and prognostic relevance.

PMID- 9272316
TI  - A comparison of ciprofloxacin and tobramycin in bacterial conjunctivitis in
      children.
AB  - A study was conducted to determine the safety and efficacy of topically applied
      ciprofloxacin ophthalmic solution in a pediatric population experiencing acute
      bacterial conjunctivitis. Topically applied ciprofloxacin (3 mg/mL) is known to
      be a safe and effective treatment for adults suffering from bacterial
      conjunctivitis; however, the safety and effectiveness of this broad-spectrum
      fluoroquinolone in pediatric patients is not well established. Ciprofloxacin was
      evaluated in a double-blind, randomized, controlled study of 257 patients ranging
      from 0 (i.e., less than 1 year) to 12 years of age from 33 geographically diverse
      medical centers. The children received either 0.3% ciprofloxacin ophthalmic
      solution (Ciloxan, Alcon Laboratories, Fort Worth, TX) or tobramycin ophthalmic
      solution (Tobrex, Alcon Laboratories, Fort Worth, TX). Both test medications were
      administered topically every 2 hours on days 1 and 2 followed by every 4 hours on
      days 3 through 7. Eyes were cultured prior to enrollment and again on day 7.
      Treatment efficacy as determined by microbiological culture data and physicians'
      judgment of overall resolution was similar for the ciprofloxacin and tobramycin
      groups. Microbiological eradication was observed in 90.1% of the ciprofloxacin
      group and 84.3% of the tobramycin group (P = 0.29). Physicians judged 87.0% of
      the ciprofloxacin patients and 89.9% of the tobramycin patients clinically cured
      on day 7 (P > 0.5). There were no serious adverse medical events attributable to
      either treatment. This study showed that topically applied ciprofloxacin
      ophthalmic solution is safe and effective in a pediatric population experiencing
      acute bacterial conjunctivitis.

PMID- 9272317
TI  - Fluoroquinolone therapy in pediatrics: where we stand.

PMID- 9272318
TI  - Sedation with intravenous midazolam in the pediatric intensive care unit.
AB  - Physical and emotional distress can have important effects on patients in the
      pediatric intensive care unit (ICU). Intravenous (IV) infusion of benzodiazepines
      is an important adjunct to assisted ventilation and other potentially distressing
      ICU procedures. Combined with intermittent or continuous infusion of opioids, the
      benzodiazepines provide smooth control of anxiety, pain, and agitation.
      Intravenous midazolam (Versed Roche Laboratories) is distinguished from diazepam
      (Valium, Roche Products) by its water solubility, short elimination half-life,
      and generally short duration of action. These pharmacological properties, which
      are also shared, in part, with the more slowly eliminated drug lorazepam (Ativan,
      Wyeth-Ayerst), facilitate titration of the rate of infusion against patient
      response and permit regulation of the depth of sedation. The major adverse
      effects of long-term benzodiazepine infusion are withdrawal symptoms and,
      occasionally, delayed awakening. The dosage needed to initiate and maintain
      sedation must be adjusted to body weight, degree of sedation desired, and
      concomitant medications, as well as to underlying health and cardiovascular
      status. Benzodiazepines, such as midazolam and lorazepam, represent important
      choices among drugs used for sedation in the pediatric ICU.

PMID- 9272319
TI  - Long-term treatment of nocturnal enuresis with desmopressin intranasal spray.
AB  - The purpose of this study was to determine the efficacy and safety of long-term
      treatment of nocturnal enuresis with desmopressin intranasal spray. Sixty-five
      children with primary nocturnal enuresis with a mean age of 11.3 years (range 7
      17) underwent a 2-week observation period followed by dose titration period of 1
      week. Those children completely dry with desmopressin entered a randomized,
      placebo-controlled, double-blind phase lasting 2 weeks, followed by a 6-month
      open treatment. The enuretic status of the children was documented for 2 weeks
      after the treatment was stopped. Eleven children had no change from baseline
      wetting with desmopressin. Thirty-two children receiving 20 mg and 9 children
      with 40 mg desmopressin were completely dry. Thirteen children were wet 1-2
      nights per week, which was better than in the pretreatment period. During the 6
      month open-treatment period, the effect of desmopressin was found to be stable.
      No side effects or adverse reactions were encountered. Two weeks after the
      treatment was stopped, 25 children were still completely dry (38% of the initial
      study population, 50% of the responders). The cure rate appeared to continue
      beyond 18 months after discontinuation of the treatment.

PMID- 9272320
TI  - Symptomatic blunt head injury in children--a prospective, single-investigator
      study.
AB  - The goal of this study was to describe a single emergency physician's experience
      with symptomatic blunt head injury in children and prospectively assess the
      sensitivity and predictive value of the neurologic examination. The author
      utilized a prospective patient series comparing neurologic examination with
      computed tomography (CT) of the head. Nine of 42 patients had intracranial injury
      for a prevalence of 21%; two patients (5%) had intracranial injury with only
      subtle neurologic examination findings. Twenty-six patients had a negative
      neurologic examination, and all had normal-appearing CT scans. Sixteen patients
      had a positive neurologic examination, of whom nine had a positive CT scan. The
      properties of the neurologic examination as a diagnostic test, with CT as the
      gold standard, were as follows: sensitivity = 100%, specificity = 78%, positive
      predictive value = 56%, negative predictive value = 100%. Normal findings from
      neurologic examination can be used in some children with symptomatic blunt head
      injury to delay or eliminate the need for CT of the head.

PMID- 9272321
TI  - Assessing parental utilization of the poison center: an emergency center-based
      survey.
AB  - The purpose of this study was to identify and characterize caretakers who fail to
      utilize the poison center for unintentional poisonings involving children. We
      interviewed 210 caretakers of children evaluated for unintentional poisoning in
      the emergency center of an urban, university-based teaching hospital to determine
      (1) whether demographic differences exist between those caretakers who contacted
      a poison center prior to the emergency center visit and those who did not and (2)
      whether differences exist in prevalence of poison prevention knowledge and
      behaviors between the two groups. Ninety-six (46%) of caretakers did not contact
      the poison center prior to the emergency center visit. Significant differences
      were found between the two groups for the following caretaker variables:
      race/ethnicity, language preference, age, level of education, country in which
      schooling occurred, and type of insurance coverage for the child. When logistic
      regression was used to control for confounding, the two variables associated with
      failure to use the poison center were black race and schooled outside the United
      States (primarily in Mexico). Poison center callers reported a higher prevalence
      of poison prevention knowledge and behaviors than noncallers. Educational
      interventions should be targeted to the groups of caretakers identified who do
      not use the poison center.

PMID- 9272322
TI  - Piperacillin-induced seizures.

PMID- 9272323
TI  - Acute renal failure from rhabdomyolysis following influenza A in a child.

PMID- 9272324
TI  - Benign recurrent intrahepatic cholestasis: improvement of pruritus and shortening
      of the symptomatic phase with rifampin therapy: a case report.

PMID- 9272325
TI  - Effect of crying on infrared tympanic temperature measurement in pediatrics.

PMID- 9272326
TI  - AAP: health supervision for children with Marfan syndrome.

PMID- 9272327
TI  - Newborn clavicle fractures.

PMID- 9272328
TI  - Prospective follow-up of children with transient hyperphosphatasemia.

PMID- 9272329
TI  - Hypertensive encephalopathy.

PMID- 9272330
TI  - Pertussis: a worldwide problem.
AB  - Pertussis is a serious disease for children in all countries, but it is more
      severe in the developing world. Disease incidence, complication rates and case
      fatality rates are highest in infants: unimmunized and incompletely immunized
      young children are also at risk in adults, pertussis is usually mild or
      asymptomatic, but older individuals may serve as reservoirs for transmission.
      Some 70 million cases of pertussis were prevented in 1994 due to immunization
      with the current whole cell vaccine. WHO emphasizes the importance of early
      completion of the primary series of vaccinations, with three doses of diphtheria
      tetanus-pertussis (DTP) vaccine one month apart starting at six weeks of age. For
      the past five years, nearly 80% of infants worldwide have received three DTP
      doses by their first birthday. Despite this, an estimated 40 million cases of
      pertussis occurred in 1994, indicating the need to increase coverage. The
      challenge is to reach 90% coverage of infants in all countries by the year 2000
      but this will require further efforts to improve immunization programmes.

PMID- 9272331
TI  - Epidemiological determinants of pertussis.
AB  - In countries with pertussis immunisation programmes, the main epidemiological
      determinant of the disease is the quality of protection induced by the vaccine
      and the coverage level achieved. Epidemiological data from England and Wales
      provide strong evidence that whole-cell pertussis vaccines can give good
      protection against both clinical disease and transmission of infection, and can
      generate herd immunity at high coverage levels. Models of pertussis transmission
      indicate that, even in the absence of waning immunity, the incidence of the
      disease is likely to increase in older age groups in countries with sustained
      high coverage. Active surveillance to detect the occurrence of pertussis in
      adults is required as the ascertainment of such cases through passive clinical
      reporting systems is low. Comprehensive post-licensing surveillance of the
      effectiveness of acellular pertussis vaccines will be essential to assess their
      long-term protection against both clinical disease and transmission of infection,
      and to determine the optimum boosting strategy.

PMID- 9272332
TI  - The United States research strategy on pertussis.
AB  - Wide-scale use of whole-cell vaccines has fed to good control of pertussis
      disease in the United States; however, this control has been achieved at the cost
      of common and uncommon adverse events of known frequencies. Agencies of the U.S.
      Public Health Service actively stimulated the development of new pertussis
      vaccines by directly supporting basic and applied research and increasing
      interactions with industry and with health authorities in other countries. This
      international cooperation resulted in a better understanding of the pathogenesis
      of pertussis and in the final development and clinical testing of several
      candidate acellular pertussis vaccines.

PMID- 9272333
TI  - European Union research strategies on vaccines.
AB  - Vaccination presents one of the most cost-effective approaches to the majority of
      infectious diseases showing strong reductions in public health costs. Vaccination
      led to the eradication of smallpox, and we are moving now close to eradicating
      polio. Vaccines might also serve as therapeutic agents against diseases such as
      herpes and novel molecular biology techniques could provide possibilities for the
      development of new vaccines against cancer. However, despite the tremendous
      progress in preventing infectious diseases by vaccination, these diseases still
      account for 17 million of the 50 million deaths in the world each year. In
      economic terms, European private and public institutions led the world in
      introducing vaccines and currently provide over 65% of the vaccine volume
      supplied to developing countries. Aware of its increasing responsibilities in
      promoting research and public health and of the challenges posed by the
      reorganization of the world market, the European Commission has launched a series
      of initiatives in vaccine research and development to encourage cooperation
      between European industry, public institutions and academia and to support common
      research projects to the benefit of every Member State and the Community as a
      whole.

PMID- 9272334
TI  - Severe adverse events in the Italian and Stockholm I pertussis vaccine clinical
      trials.
AB  - The rates of severe side reactions observed in Stockholm I and Italian Trials are
      reported. Children vaccinated with the same DTPwc in both trials experienced high
      fever and persistent crying more frequently than in any other group, while
      similar rates for all the severe side reactions were observed among DTaPs and DT
      vaccines. Recipients of different DTaP vaccines showed similar rates of severe
      reactions, which did not differ from recipients of DT vaccines, either in Sweden
      or Italy.

PMID- 9272335
TI  - Severe adverse events in a comparative efficacy trial in Germany in infants
      receiving either the Lederle/Takeda acellular pertussis component DTP (DTaP)
      vaccine, the Lederle whole-cell component DTP (DTP) or DT vaccine. The Pertussis
      Vaccine Study Group.
AB  - Severe adverse events were evaluated in a comparative efficacy trial in Germany
      in infants who received either the Lederle/Takeda acellular pertussis component
      DTP (DTaP) vaccine, the Lederle whole-cell component DTP (DTP) or DT vaccine.
      Vaccinees received four doses (at three, four-and-a half, six and 15-18 months of
      age) of either DTP or DTaP vaccine or three doses at three, four-and-a half and
      15-18 months of age) of DT vaccine. The analysis included 4,273 DTaP recipients,
      4,259 DTP recipients and 1,739 DT vaccinees. Convulsions within three days of
      vaccination occurred in 1/15,912 doses in DTaP recipients and 1/3,926 doses in
      DTP vaccinees (p = 0.22). Persistent inconsolable crying was more common in DTP
      vaccinees (1/113 doses) compared with DTaP (1/497 doses, p < 0.001) and DT (1/359
      doses, p < 0.001) recipients. High fever (< or = 40.5 degrees C) was less
      frequent in DTaP vaccinees (1/16,239 doses) compared with DTP (1/5,359) and DT
      recipients (1/4,665). One hypotonic-hyporesponsive episode was observed.

PMID- 9272336
TI  - The Senegal pertussis trial: safety and surveillance of adverse reactions.
AB  - In the Senegal pertussis trial, common adverse reactions were actively monitored
      during the pilot phase II study, while the frequency of severe adverse reactions
      was monitored as a secondary objective within the phase III efficacy trial. Since
      the trial was conducted in Niakhar, an area in rural West Africa under intensive
      surveillance, the safety monitoring during the study was incorporated within the
      general surveillance system. This was a two-step procedure: detection of a
      potential reaction by a field worker, followed by confirmation report by a
      physician. The frequency of severe reactions was low among both pertussis vaccine
      groups, receiving either the two-component acellular vaccine or the whole-cell
      vaccine currently used in the Senegal Expanded Programme on immunisation. Among
      severe reactions, only persistent crying was found to be at a significantly
      higher rate in the whole-cell group. Common adverse reactions were more frequent
      in the whole-cell group.

PMID- 9272337
TI  - Safety evaluation of one whole-cell and three acellular pertussis vaccines in
      Stockholm trial II.

PMID- 9272338
TI  - Hypotonic hyporesponsive episodes in eight pertussis vaccine studies.

PMID- 9272339
TI  - Common side effects in the Italian and Stockholm I trials.
AB  - We have compared the frequency of common side effects observed following
      vaccination in the Italian and Stockholm I Trials. A higher proportion of DTPwc
      vaccinees in the two trials experienced side effects compared with DTaP and DT
      vaccinees. Fever, local redness and tenderness were more frequently observed in
      all study groups in the Stockholm I Trial when compared to the Italian Trial.
      Despite the similarities in study design, parental recall bias, site of
      injection, simultaneous administration of other vaccines, and antipyretic use
      could have played a role in the differences observed.

PMID- 9272340
TI  - Adverse reactions of a pertussis toxoid vaccine in a double-blind placebo
      controlled trial.
AB  - In the Gothenburg study, 3,450 infants were randomly assigned to receive three
      subcutaneous injections of acellular pertussis vaccine consisting of peroxide
      inactivated pertussis toxin with diphtheria and tetanus toxoids (DTP-toxoids) or
      DT-toxoids alone under blind conditions at three, five and 12 months of age.
      Safety of the vaccinations was assessed by direct contact with the families in
      the week following each injection. No serious vaccine-associated adverse
      reactions were observed, in either group. The frequency of fever and local
      reactions increased by dose. Redness and swelling were slightly but significantly
      more frequent in recipients of DTP-toxoids compared to the DT group.

PMID- 9272341
TI  - Minor adverse events in a comparative efficacy trial in Germany in infants
      receiving either the Lederle/Takeda acellular pertussis component DTP (DTaP)
      vaccine, the Lederle whole-cell component DTP (DTP) or DT vaccine. The Pertussis
      Vaccine Study Group.
AB  - Minor adverse events were evaluated in a comparative efficacy trial in Germany in
      infants who received either the Lederle/Takeda acellular pertussis component DTP
      (DTaP) vaccine, the Lederle whole-cell component DTP (DTP) or DT vaccine.
      Vaccinees received four doses (at three, four-and-a half, six and 15-18 months of
      age) of either DTP or DTaP vaccine or three doses (at three, four-and-a half and
      15-18 months of age) of DT vaccine. The reactogenicity analysis included 4,273
      DTaP, 4,259 DTP and 1739 DT vaccinees. Local reactions (erythema and induration)
      and systemic events (fever, fretfulness, drowsiness and anorexia) were more
      common after each dose of DTP vaccine than after the DTaP and DT vaccine doses.
      Erythema, induration and fever increased in frequency in DTaP and DT recipients
      with increasing series number. Erythema, induration and fever after the first two
      doses of vaccine were more frequent in DT recipients than DTaP vaccinees.
      Antipyretics were more commonly used in DTP recipients than in DTaP vaccinees.

PMID- 9272342
TI  - Implications of different study designs for the evaluation of acellular pertussis
      vaccines.
AB  - Twelve different pertussis vaccines (eight of them acellular) have been evaluated
      in seven different studies planned to provide absolute or relative efficacy
      measures. Study designs included trials with randomized unvaccinated (DT) and/or
      whole-cell vaccine control groups, a cohort study, household contact studies and
      a case-control study. Although some of the studies were designed only to provide
      relative measures comparing the efficacy of an acellular versus a whole-cell
      vaccine, striking variation in the efficacy of the whole-cell vaccines led all
      studies to emphasize estimates of absolute efficacy. The reliability of the
      various results is likely to be dependent upon details of the study designs. In
      particular three randomized, placebo-controlled, double-blind trials (carried out
      in Italy and Sweden) provide the most convincing results through their avoidance
      of selection bias in the (unvaccinated) baseline control groups. Problems in
      differential case ascertainment were inherent in all studies. This paper reviews
      the design of each of the studies and comments on methodological problems likely
      to have influenced their findings.

PMID- 9272343
TI  - Case definitions.
AB  - The definition of a case of pertussis is an essential point in evaluating and
      comparing the results from the seven studies on pertussis vaccines presented at
      the Symposium. An assessment of the impact of case definition on the evaluation
      of vaccine efficacy has been performed on the Italian data-set, by comparing the
      clinical presentation of cough illnesses which were laboratory-confirmed as B.
      pertussis infection with those not-confirmed, by study vaccine. The results show
      that the estimate of vaccine efficacy is greatly variable by the choice of case
      definition and dependent on the study design. The assessment of the effect of
      each vaccine should be performed by using various clinical endpoints and the
      method used in detection of suspected cases in each study should be carefully
      evaluated to verify comparability of results.

PMID- 9272344
TI  - Preparation and composition of acellular pertussis vaccines. Consideration of
      potential effects on vaccine efficacy.
AB  - An evaluation of possible relationships between the preparation and content of
      acellular pertussis vaccines and their efficacy reveals that, in most instances,
      there is much more extensive variability in content and mode of preparation of
      these products than in their clinical efficacies. In general, there is a positive
      correlation of antigen content with immunogenicity. However, there was an
      apparent difference in the dose-response relationships between chemically and
      genetically toxoided vaccines which revealed a greater immunogenicity of the
      genetically inactivated material. Overall, however, the immunigenicity data (IgG
      serology) do not correlate well with protective efficacy and it is apparent that
      additional information is necessary to elucidate a specific role for any aspect
      of vaccine content or preparation in vaccine efficacy.

PMID- 9272345
TI  - Absolute efficacy of acellular pertussis vaccines in household settings.
AB  - Household studies in the two recently concluded Swedish pertussis vaccine
      efficacy trials demonstrated that one monocomponent and one five-component
      candidate acellular pertussis vaccine had reasonably good protective efficacy
      against clinically typical pertussis after household exposure. Another recently
      concluded German household study, led from Mainz, also demonstrated reasonably
      good efficacy for a three-component acellular pertussis vaccine. The methods of
      case ascertainment and duration of follow-up had a marked influence on the
      efficacy estimates of another candidate two-component acellular pertussis
      vaccine. This vaccine and a U.S. licensed commercial whole-cell vaccine had very
      low efficacy against pertussis infection after household exposure. Differences in
      methodology preclude direct comparisons between the efficacy estimates obtained
      in various household studies.

PMID- 9272346
TI  - Estimation of pertussis vaccine efficacy in the presence of covariates in three
      randomized trials.
AB  - We estimated efficacy of pertussis vaccines in three randomized controlled trials
      with adjustment for several baseline covariates: presence of one or more other
      children in the household, sex of the study child, and geographical area.
      Adjusted and unadjusted efficacy estimates differed only trivially. We also
      assessed the association of efficacy with time since vaccination and background
      pertussis incidence. The acellular vaccines, except for the two-component vaccine
      in the Stockholm trial, appeared to maintain their efficacy during two years of
      follow-up. In contrast, efficacy of a whole-cell vaccine decreased significantly
      in both the Stockholm and Italian trials. The relationship between efficacy and
      background incidence was not consistent across studies and vaccines.

PMID- 9272347
TI  - Absolute and relative efficacy of whole-cell vaccines.

PMID- 9272348
TI  - The effectiveness of whole-cell pertussis vaccines.
AB  - The acellular pertussis vaccine efficacy trials revealed significant facts
      concerning the whole cell vaccines used as controls. At least three whole-cell
      vaccines were shown to have considerable efficacy, and in fact superior efficacy
      to the acellular vaccines to which they were compared. One whole-cell vaccine,
      previously shown to be poorly immunogenic after three doses, was correspondingly
      low in protective efficacy. Although acellular vaccines may be preferred in some
      countries because of their lower reactogenicity, we are faced with the fact that
      a well-prepared whole-cell vaccine still provides the best protection against
      pertussis.

PMID- 9272349
TI  - Factors influencing the analysis of secondary prevention of pertussis.
AB  - The aim of this study was to evaluate factors that influenced the spread of
      pertussis in secondary contacts after household exposure. The data were acquired
      during a prospective household-contact study into the efficacy of an acellular
      vaccine. The spread of the disease was monitored with respect to various case
      definitions of pertussis, socio-economic factors, household composition, and
      antibiotic therapy. A total of 453 index cases had contact with 173 unvaccinated
      children aged from 6 to 47 months. Depending on the clinical case definition, the
      attack rates (AR) in children with a laboratory-confirmed Bordetella infection
      increased from 55% for the WHO definition to 69%, when a less stringent
      definition was used. AR in children were independent of age and gender. The
      social status of the family had no significant influence on the AR in children.
      Erythromycin treatment of the index case reduced the AR from 64% to 51% (p =
      0.08). These factors should be taken into consideration when studies into the
      secondary prevention of pertussis by acellular vaccines are initiated.

PMID- 9272350
TI  - The role of Bordetella pertussis infections in adults in the epidemiology of
      pertussis.
AB  - In six of the seven efficacy studies, cases of pertussis in adults were
      diagnosed. In particular, primary cases in adults were common in study families
      in the Mainz and Erlangen studies. Recent epidemiological studies indicate that
      B. pertussis infections in adults are common and endemic. It is suggested that B.
      pertussis circulation cannot be controlled by immunization of children but that
      acellular vaccines make it possible to give booster immunizations to adults. An
      adult booster programme might decrease the circulation of B. pertussis in adults
      and could lead to the elimination of the organism from the population.

PMID- 9272351
TI  - A comparison of enzyme immunoassays used to measure serum antibodies to
      components of Bordetella pertussis.
AB  - To evaluate the comparability of immunoassays, the Center for Biologics
      Evaluation and Research organized an international collaborative study in which
      33 laboratories participated. For a coded panel of 21 samples, each laboratory
      measured IgG antibodies to specific proteins of Bordetella pertussis using assay
      systems currently in place. Analyses were performed to evaluate the assay
      precision and the quantitative agreement among laboratories. Data from a subset
      of 12 laboratories are used to illustrate points relevant to the use of
      immunoassays in seven vaccine efficacy studies. Differences among the
      laboratories in assay precision for samples with known two-fold differences
      indicate that serological case definitions must take into consideration the
      characteristics of the assays and the concentration of antibody in the samples.
      Assays performed in different laboratories to assess vaccine immunogenicity may
      generate similar results but critical comparisons will probably require samples
      to be tested in the same laboratory at the same time.

PMID- 9272352
TI  - Diagnostic pertussis serology in the recent clinical efficacy studies of
      acellular vaccines.
AB  - The laboratory routine used and the criteria applied for serological case
      confirmation in vaccine efficacy trials have a direct influence on the
      identification of cases, which consequently may also affect the estimation of
      vaccine efficacy (VE). Some differences in the application of serological
      confirmation criteria among the recent clinical studies of pertussis vaccines
      include the level of increase in titre and use of single specimen diagnostics.
      Additionally, the use of pre-exposure serum specimen collections increases the
      sensitivity of serological confirmation. In the 1992-95 Stockholm trial, a
      regimen to collect serum samples systematically was introduced; using acute- and
      convalescent-phase sera from the cough episodes, the proportion of all cases
      which were serologically confirmed was 25%. When pre-exposure sera were also
      available, the proportion was 35%; the increased sensitivity was differential by
      vaccine group and affected the estimated VE to some extent. Therefore, with the
      different application of serological methods among the various efficacy studies,
      direct comparisons between studies should be made with great caution.

PMID- 9272353
TI  - Serological responses to infection with B. pertussis.
AB  - The results of serological assays performed during the Italian controlled
      efficacy trial of two acellular vaccines and one whole-cell vaccine against
      pertussis are described and discussed. We examined 312 episodes of suspected
      pertussis disease confirmed by B. pertussis isolation, and 2862 episodes without
      any evidence of B. pertussis or B. parapertussis infection. Higher mean log ELISA
      titres for IgG to pertussis toxin (PT) were found in the acute-phase serum
      specimens of those children vaccinated with the acellular pertussis vaccines and
      particularly in the SmithKline Beecham DTaP vaccine group. These apparently
      anamnestic responses were responsible for the observed differences in ELISA
      diagnostic sensitivity exhibited by IgG to PT and by IgG to filamentous
      haemagglutinin (FHA). We observed minimal IgA responses to PT but vigorous IgA
      responses to FHA in the convalescent-phase serum specimens for the acellular
      pertussis vaccine groups, which contributed to the sensitivity of the serological
      series of assays for diagnostic purposes.

PMID- 9272354
TI  - Differences by antigen in seroconversion: sensitivity, specificity and bias in
      the serological confirmation of pertussis.
AB  - Vaccine efficacy of the most efficacious acellular pertussis vaccines in the
      three recent placebo-controlled clinical trials, when estimated using the primary
      clinical case criterion, does not change substantially with the inclusion of
      serological confirmation in addition to culture confirmation. In the Italy trial,
      because of relatively high anti-PT antibody levels at the time of the acute-phase
      specimen in episodes of 21 or more days of paroxysmal cough, significant
      increases in antibody to PT are less likely to be seen in the acellular vaccine
      groups when evaluating children with bacterial isolation. However, the effect of
      this decreased sensitivity appears to be compensated by significant antibody
      increases in the FHA assay. When projecting a maximally sensitive criterion for
      serological assessment using the observed decreases in IgG antibody to PT over
      time following primary vaccination stratified by vaccine group, and comparing the
      expected antibody level with the observed level in the convalescent-phase
      specimen, the effect on estimated vaccine efficacy is minimal.

PMID- 9272355
TI  - Isolation, identification and characterization of Bordetella pertussis.
AB  - During the pertussis clinical trials, the best conditions for isolating B.
      pertussis were determined. Isolation is higher if two nasopharyngeal aspirates
      are collected, transport is carried out at ambient temperature and takes no
      longer than 48 hours, Reagan Lowe or Bordet Gengou selective and non-selective
      plates are used and incubated at 36 degrees C for seven days. Identification must
      include Gram stain and urease, oxidase and nitrate reactions. Confirmation is
      obtained with specific anti-B. pertussis antiserum. Characterization of the
      isolates can be performed by using the polymerase chain reaction, serotyping and
      pulsed-field gel electrophoresis.

PMID- 9272356
TI  - Bordetella pertussis serotype of clinical isolates in Sweden during 1970-1995 and
      influence of vaccine efficacy studies.
AB  - During the years 1970 to 1995, the serotypes of collected clinical isolates from
      the different regions of Sweden were examined. Vaccination using whole-cell
      pertussis vaccine decreased during the year preceding cessation of general
      vaccination of children in 1979. Although the total number of clinical isolates
      examined was limited up to 1978 compared to later years, serotype 1, 2, 3
      clinical isolates generally predominated. During periodical pertussis outbreaks,
      serotype 1, 3 strains were isolated, the proportion of which was about equal to
      that of serotype 1, 2, 3 isolates. Following cessation of general vaccination in
      1979, the proportion of both serotypes 1, 2, 3 and 1, 3 isolates gradually
      diminished, together contributing about 20 percent of the total number of
      isolates in 1995. Clinical isolates of serotype 1, 2 were identified in the year
      1977, just before cessation of general vaccination in Sweden using whole-cell
      vaccine. Since then, this serotype has gradually increased to over 80 percent of
      total isolates in 1995, possibly indicating that the use of whole-cell pertussis
      vaccine was effective against this serotype or that the vaccine influenced
      serotype expression. Vaccine efficacy studies conducted in Sweden during 1986-87
      using one and two-component vaccines (BIKEN) and in 1994-95 using two-component
      (SmithKline Beecham Pharmaceuticals) and five-component (Connaught Laboratories,
      Ltd.) vaccines are examined with the object of studying whether the vaccines
      showed any influence on the different serotypes of B. pertussis causing disease.

PMID- 9272357
TI  - Diagnostic polymerase chain reaction.
AB  - In this overview, the PCR sensitivities and specificities for diagnosis of B.
      pertussis in seven different pertussis vaccine studies are discussed. The
      performance sensitivity of the PCR methods ranged from < or = 1 to 10 cfu, and
      the diagnostic sensitivity from 73 to 100% when culture was used as a reference.
      The proportional increase in cases by positive PCR among culture-negatives ranged
      from 71 to 293% (four trials), whereas the gain was 6 to 11% among culture and
      serology-negatives (two trials). As the triggers for collecting nasopharyngeal
      samples, the selection of samples for PCR analysis, and the PCR protocols
      themselves differed between the trials, these figures must be interpreted with
      caution. However, the overall results indicate a considerable gain in sensitivity
      when PCR was added to culture, but a moderate gain in addition to serology.

PMID- 9272358
TI  - Bordetella parapertussis infections.
AB  - The rate of isolation of Bordetella parapertussis among children with cough
      during the follow-up of different clinical efficacy studies has been evaluated.
      In the Italian trial, a comparison of clinical characteristics between B.
      pertussis and B. parapertussis infections showed lower frequencies and shorter
      duration of typical symptoms of whooping cough such as paroxysmal coughing,
      whooping, and vomiting in the group of children affected with B. parapertussis
      infections. In about 70% of B. parapertussis infections, there was a two-fold
      increase of IgA or IgG anti-FHA from acute- and convalescent-phase serum
      specimens. The analysis of the distribution of B. parapertussis cases in children
      fully immunized with each pertussis vaccine suggested that vaccination is
      irrelevant in preventing B. parapertussis infection.

PMID- 9272359
TI  - Comparison of serological results in the NIAID Multicenter Acellular Pertussis
      Trial with recent efficacy trials.
AB  - Comparison of the serological results from the NIAID-funded Multicenter Acellular
      Pertussis Trial (MAPT) and the efficacy trials are complicated by differences in
      assay methods, immunization schedules, vaccine lots and populations immunized. In
      spite of these differences, serological results closely approximating those
      obtained in the MAPT were found for most or all of the assayed antibodies in the
      Mainz and Erlangen studies. Serological results for some of the antigens included
      in the vaccines used in the Italian and Stockholm trials were similar to the MAPT
      results, while significant differences were noted with other antigens.
      Differences in immunization schedules and serological assay methods made
      comparisons between MAPT and the Gothenburg and Senegal trials more difficult.
      Our understanding of the efficacy trial results, and our ability to apply those
      results to the U.S. population, would be enhanced markedly by simultaneous re
      analysis of stored sera from MAPT and selected efficacy trials. This goal should
      be given priority by the study organizers and sponsors.

PMID- 9272360
TI  - Antibody kinetics and long-term sero-prevalence in the Italian clinical trial of
      acellular pertussis vaccines.
AB  - In the Italian Pertussis Vaccine Trial, data were collected to evaluate the
      persistence of anti-pertussis antibodies. A sub-cohort of 1275 children was
      followed for this purpose until a mean age of 21 months. An additional evaluation
      included pooled cross-sectional analysis of serum specimens collected for
      analysis of cough illnesses. Antibodies to PT, FHA and PRN were measured by ELISA
      using a standardized technique. With both acellular vaccines in the study (the
      Chiron Biocine three-component and SmithKline Beecham three-component vaccines)
      there was a fast and steep decrease of mean geometric titres for PT, FHA and PRN
      in the months immediately following vaccination. Titres were close to the
      detection limit 15 months after the end of primary immunization. The
      immunogenicity of the whole-cell study vaccine (produced by Connaught
      Laboratories, Inc. Swiftwater, USA) was poor as determined one month after the
      third dose and no antibody was detected in nearly all children 15 months after
      the end of vaccination.

PMID- 9272361
TI  - Factors influencing antibody responses to acellular pertussis vaccines.
AB  - There are several factors which can potentially affect the immune response of
      humans to vaccination with acellular pertussis vaccines. The only way to study
      these responses at present is by serology. Only for a few of these factors has
      the effect on humoral immunogenicity been studied in any way, making conclusions
      difficult. Nonetheless, at least gender and pre-existing, maternal antibody
      appear not to influence the serological response to acellular pertussis
      vaccination.

PMID- 9272362
TI  - Methods for estimating serological correlates of protection.

PMID- 9272363
TI  - Bordetella pertussis-specific Th1/Th2 cells generated following respiratory
      infection or immunization with an acellular vaccine: comparison of the T cell
      cytokine profiles in infants and mice.
AB  - In an investigation of cell-mediated immunity against Bordetella pertussis, we
      found that B. pertussis infection in infants and in mice was associated with the
      induction of antigen-specific T cells that secrete IFN-g and IL-2, but not IL-4
      or IL-5. This cytokine profile is characteristic of Th1 cells that mediate
      cellular immune responses against a range of intracellular pathogens. An
      examination of cytokine production following immunization with a three-component
      acellular vaccine, comprising inactive PT, FHA and pertactin adsorbed to alum,
      demonstrated that spleen cells from vaccinated mice produced high levels of IL-5,
      but no detectable IFN-g and low levels of IL-2. In contrast, peripheral blood
      mononuclear cells from vaccinated infants produced IL-2, IL-5 and IFN-g. These
      findings highlight significant differences in the immune responses generated by
      vaccination and natural infection with B. pertussis and demonstrate that the T
      cell response induced with an acellular vaccine, although dominated by type 2
      cytokines in mice, is more heterogeneous in infants with a Th0 or mixed Th1/Th2
      cytokine profile.

PMID- 9272364
TI  - Cell-mediated immunity after pertussis vaccination and after natural infection.
AB  - The aim of this study was the investigation of the specific cell-mediated (CMI)
      responses induced by DTaP and to compare these data to immunity after natural
      infection. The ability of peripheral blood T-lymphocytes to respond to the
      pertussis related antigens pertussis-toxin (PT), filamentous haemagglutinin
      (FHA), and Pertactin (PRN) was investigated in 40 children before vaccination and
      at different times after vaccination with DTaP (Infanrix) by measurement of
      antigen-specific proliferation, lymphocyte phenotype, cytokine production and
      expression of activation markers (CD25, HLADR). Similar investigations were
      performed in children 4-6 weeks after recovery from natural pertussis. DTaP
      created a specific T-cell-response to PT, FHA and PRN that increased continually,
      depending on the progress of the vaccination schedule. In contrast to waning
      antibody titres, CMI was stable even between the post-basic vaccination and the
      pre-booster period. The magnitude of CMI after DTaP equalled those after natural
      infection. Measurement of cytokine-pattern showed induction of IFN-tau-producing
      T-helper-1-cells with lower stimulation of IL 10-producing T-helper-2-cells for
      DTaP and natural infection. Our data indicate that DTaP-vaccination induces a
      potent immune response to PT, FHA, and PRN at least equivalent to CMI after
      natural infection. The finding of a preferential T-helper-1-induction after DTaP
      and natural infection suggests a role of IFN gamma-activated macrophages in the
      protective response against B. pertussis-induced disease.

PMID- 9272365
TI  - Acellular vaccines induce cell-mediated immunity to Bordetella pertussis antigens
      in infants undergoing primary vaccination against pertussis.
AB  - The induction of cell-mediated immunity (CMI) to Bordetella pertussis antigens
      (whole, heat-inactivated bacterial cells [BPC], pertussis toxin [PT], filamentous
      haemagglutinin [FHA], pertactin [PRN]) was assessed by a lymphoproliferation
      assay in vitro in a cohort of children enrolled in a randomized clinical trial of
      pertussis vaccines efficacy in Italy. Four vaccination groups were compared:
      children receiving acellular pertussis (aP) vaccines from SmithKline Beecham (SB)
      or Chiron Biocine (CB) or whole-cell vaccine (wP) from Connaught, each combined
      with diphtheria and tetanus toxoids (DT), or a DT vaccine only. When the purified
      antigens were used, statistically significant differences in CMI responses were
      observed between pre- and post-vaccination samples. In particular, CMI responses
      to FHA and PRN were detected in the majority of both aP vaccines recipients,
      whereas DTwP-recipients were CMI-positive in a much lower proportion. Clear-cut
      differences in PT responses were detected between DTwP and DTaP vaccine
      recipients, in favour of the latter. These differences were maintained up to 24
      months after completion of the primary vaccination schedule. Thus, CMI responses
      could be a useful adjunct to serology in studying the immune responses to
      pertussis vaccines.

PMID- 9272366
TI  - Examination of similarities between diphtheria and pertussis and their toxoids
      provide insight into vaccine-induced protection to Bordetella pertussis.

PMID- 9272367
TI  - Japanese experience with 60 million doses of acellular pertussis vaccines.

PMID- 9272368
TI  - Epidemiology of pertussis and use of acellular pertussis vaccines in Japan.

PMID- 9272369
TI  - A consideration of control requirements for acellular pertussis vaccines.

PMID- 9272370
TI  - Regulatory and standardization issues.

PMID- 9272371
TI  - Public health application of acellular pertussis vaccines.

PMID- 9272372
TI  - Acellular pertussis vaccines: the next step.

PMID- 9272373
TI  - Public health implications: United Kingdom.

PMID- 9272374
TI  - Safety of acellular pertussis vaccine: follow-up studies.

PMID- 9272375
TI  - Issues regarding future research on pertussis vaccines.

PMID- 9272376
TI  - Are serological responses to acellular pertussis antigens sufficient criteria to
      ensure that new combination vaccines are effective for prevention of disease?
AB  - Combining several vaccines in a single formulation can alleviate the increasing
      complexity of the paediatric vaccination schedule. However, vaccine antigens that
      are highly effective when administered singly may lose potency in combination;
      consequently, the efficacy of each component must be established for any new
      proposed combination vaccine. When the serological response to a vaccine
      correlates clearly with clinical efficacy, the efficacy of that component in a
      combination can be inferred from immunogenicity studies. Poliovirus, tetanus and
      diphtheria toxoids, Haemophilus influenzae type b and Neisseria meningitidis, and
      hepatitis B vaccines, can all be assessed in this manner. Unfortunately, the
      antibody titres induced by acellular pertussis vaccines do not correlate with
      vaccine efficacy. Thus, although diphtheria-tetanus-acellular pertussis (DTaP)
      vaccine has been considered a prime building block in the development of new
      combination vaccines, modifying DTaP by the addition of new vaccine components
      may decrease the ability of the vaccine to protect against pertussis without a
      change in serum antibody response. For this reason, immunogenicity is not an
      adequate or safe basis for licensing combination vaccines containing acellular
      pertussis. Development and licensing of new combination vaccines containing
      components with serological correlates of clinical efficacy can proceed more
      rapidly than DTaP-based combinations and should be pursued.

PMID- 9272377
TI  - Increased collateral blood flow to ischemic myocardium by estrogen replacement
      therapy may contribute to reduced incidence of fatal and non-fatal acute
      myocardial infarction in postmenopausal women.

PMID- 9272378
TI  - Expression of a chemotactic cytokine (MCP-1) in cerebral capillary endothelial
      cells in vitro.
AB  - A full-length cDNA encoding the porcine monocyte chemoattractant protein-1 (pMCPC
      1) was isolated from growth-stimulated porcine cerebral capillary endothelial
      cells (cEC); the pMCP-1 cDNA showed 89% identity to human MCP-1 and was isolated
      by use of subtractive hybridization and differential screening of two
      phenotypically different sub-populations of cloned cEC. pMCP-1 was abundantly
      expressed in cEC grown in the presence of FCS, ECGF and heparin whereas lower
      expression was observed in cEC kept in FCS-supplemented medium only. As shown by
      Northern blot analysis, no pMCP-1 transcripts were present in total RNA derived
      from freshly isolated brain capillaries, large brain vessels or whole brain
      homogenate. MCP/JE expression was also demonstrated in ECGF/heparin-treated
      murine cEC. Astrocytes and smooth muscle cells grown in FCS-supplemented medium
      did not show MCP-1 expression. Treatment of porcine cEC with TNF-alpha increased
      pMCP-1 mRNA levels in a dose-dependent manner. These data further support the
      notion that cerebral capillary endothelial cells actively participate in
      processes of CNS host defense.

PMID- 9272379
TI  - Role of adenosine in the hypoxic induction of vascular endothelial growth factor
      in porcine brain derived microvascular endothelial cells.
AB  - Hypoxia induced the mRNA expression of vascular endothelial growth factor (VEGF)
      in porcine brain derived microvascular endothelial cells (BMEC) in a time
      dependent manner. Corresponding to the mRNA induction the protein level of VEGF
      was elevated during hypoxia. The adenosine A1 receptor antagonist 8
      phenyltheophylline (8-PT) reduced the hypoxia-induced VEGF mRNA and protein
      expression significantly. The treatment of BMEC with cobalt chloride-known to
      activate an oxygen sensing mechanism similar to the one used by the
      erythropoietin gene-also induced the VEGF mRNA expression, but 8-PT did not
      reduce this VEGF induction. Although, earlier studies revealed that agents like
      phorbolester induced the VEGF mRNA expression, the specific inhibitor of the
      proteinkinase C (PKC) bisindolylmaleimide (BIM) did not reduce but enhanced the
      hypoxia-induced VEGF mRNA expression. These results indicate that the VEGF
      induction in BMEC can proceed through PKC-dependent and -independent pathways
      (like those acting via the putative oxygen sensor). Hypoxia in BMEC probably
      activates the PKC-dependent pathway mainly via adenosine which might be formed
      during hypoxia and thereby inhibits activation of PKC-independent, oxygen
      sensing, pathways. This suggestion was supported by the fact that hypoxia as well
      as adenosine increased the VEGF mRNA expression post-transcriptionally by
      enhancing the stability of the VEGF mRNA [corrected].

PMID- 9272380
TI  - The role of thromboxane A2 in the altered microvascular reactivity in two-kidney,
      one-clip hypertension.
AB  - To investigate the nature of the arachidonic acid metabolite involved in the
      altered reactivity of microvessels of two-kidney, one-clip hypertensive rats and
      the possible contribution of this product to the elevated blood pressure levels
      found in two-kidney, one-clip hypertension, mesenteric arterioles either perfused
      in vitro or studied in vivo were used along with blood pressure determinations.
      The decreased response to acetylcholine observed was normalized by ridogrel, a
      thromboxane A2 receptor antagonist, and dazoxiben, a thromboxane A2 synthase
      inhibitor. The smooth muscle response to nitric oxide, tested with sodium
      nitroprusside, was unaltered in two-kidney, one-clip hypertensive microvessels.
      Neither ridogrel nor dazoxiben modified the response to this vasodilator. In
      contrast, the potentiated response to noradrenaline was corrected by ridogrel and
      dazoxiben in vitro but not in vivo. Noradrenaline and acetylcholine increased the
      release of thromboxane A2 from the mesenteric microvessels of two-kidney, one
      clip hypertensive rats. Ridogrel and dazoxiben decreased but did not normalize
      the elevated blood pressure of hypertensive rats. Based on these results, we
      concluded that: 1) the decreased responsiveness of smooth muscle to acetylcholine
      resulted from an increase in thromboxane A2 formation rather than a decrease in
      sensitivity to nitric oxide; 2) thromboxane A2 contributes to the increased
      noradrenaline response in mesenteric microvessels perfused in vitro while in in
      vivo other blood borne vasoactive agents may also be involved since the
      potentiated noradrenaline response was not corrected by inhibiting thromboxane A2
      synthesis or receptors; 3) in addition to thromboxane A2, another as yet
      unidentified factor, may contribute to the elevated blood pressure in two-kidney,
      one-clip hypertension.

PMID- 9272381
TI  - Dissociation characteristics of endothelin receptor agonists and antagonists in
      cloned human type-B endothelin receptor.
AB  - The human type-B endothelin receptor (h-ETB) was cloned from human lung poly
      A+RNA and stably expressed in CHO cells. Endothelin (ET) receptor binding and
      stimulation of PI hydrolysis demonstrated that the cloned h-ETB receptor is
      functional and linked to intracellular signal transduction pathways in CHO cells.
      The molecular mass of the h-ETB receptor was determined to be 65 KDa, and Bmax
      and Kd were 0.36 pmol/mg and 80 pM, respectively. Competition studies employing
      receptor ligands revealed that the potencies of the test ligands (IRL1620,
      PD142893, and Ro46-2005) were dependent on the length of the incubation time,
      whereas the natural agonists (ET-1 and ET-3) were not. When competing with ET-1
      in the h-ETB receptor binding, the IC50 increased from 1.2 nM to 8.2 nM for
      IRL1620, 0.068 microM to 1.9 microM for PD142893, and 0.76 microM to 12.7 microM
      for Ro46-2005, as the incubation time increased from 1 hr to 24 hr. These time
      induced changes are likely due to differences in the dissociation characteristics
      between the artificial ligands and the natural ligands.

PMID- 9272383
TI  - Endothelial cell expression of testican mRNA.
AB  - By screening random cDNAs from a continuous vascular endothelial cell line,
      EA.hy926, we identified a 5 kb mRNA that is expressed at high levels by this
      human cell line and by an early passage umbilical vein endothelial cell line. It
      is detected at lower levels in certain stromal cell lines, but it is not detected
      in most other cell lines tested, indicating that it represents a differentially
      expressed function rather than a ubiquitous or housekeeping function. This mRNA
      was readily detected in samples derived from most human organs as might be
      expected for a gene expressed in the vascular wall. Sequencing of the 5 kb mRNA
      reveals its identity with 3.5 kb of previously published testis-derived cDNA
      sequence called testican (Alliel et al., 1993). Differential expression of this
      gene by endothelial cells contributes a new perspective on the potential function
      of testican.

PMID- 9272382
TI  - Low-density lipoprotein stimulated peroxide production and endocytosis in
      cultured human endothelial cells: mechanisms of action.
AB  - The effects of arachidonic acid metabolism and NADPH oxidase inhibitor on the
      hydrogen peroxide (H2O2) generation and endocytotic activity of cultured human
      endothelial cells (EC) exposed to atherogenic low-density lipoprotein (LDL)
      levels have been investigated. EC were incubated with 240 mg/dl LDL cholesterol
      and cellular H2O2 production and endocytotic activity measured in the presence
      and absence of the arachidonic acid metabolism inhibitors, indomethacin,
      nordihydroguaiaretic acid, and SKF525A, and NADPH oxidase inhibitor, apocynin.
      All inhibitors, with the exception of indomethacin, markedly reduced high LDL
      induced increases in EC H2O2 generation and endocytotic activity. EC exposed to
      exogenously applied arachidonic acid had cellular functional changes similar to
      those induced by high LDL concentrations. EC incubated with 1-25 uM arachidonic
      acid had increased H2O2 production and heightened endocytotic activity. Likewise,
      EC pre-loaded with [3H]arachidonic acid when exposed to increasing LDL levels (90
      330 mg/dl cholesterol) had a dose-dependent rise in cytosolic [3H]arachidonic
      acid. The phospholipase A2 inhibitors, 4-bromophenacyl bromide and 7,7
      dimethyleicosadienoic acid, markedly inhibited H2O2 production in EC exposed to
      240 mg/dl LDL cholesterol. These findings suggest that arachidonic acid
      contributes mechanistically to high LDL-perturbed EC H2O2 generation and
      heightened endocytosis. Such cellular functional changes add to our understanding
      of endothelial perturbation, which has been hypothesized to be a major
      contributing factor in the pathogenesis of atherosclerosis.

PMID- 9272385
TI  - Sequential treatment of deep fungal infections with amphotericin B deoxycholate
      and amphotericin B colloidal dispersion.
AB  - Amphotericin B colloidal dispersion (ABCD) is a novel lipid formulation of
      amphotericin B designed to diminish toxic effects of the drug. In the following
      report, nine cases of suspected (n = 4) and proven (n = 5) deep Candida
      infection, treated sequentially with amphotericin B deoxycholate and ABCD, are
      presented. The treatment was successful in seven cases. During treatment with
      amphotericin B deoxycholate, a rise in serum creatinine was observed in seven
      patients, hypokalemia in five, and metabolic acidosis in four. After replacing
      amphotericin B deoxycholate with ABCD, laboratory parameters improved in four of
      the seven patients with increased creatinine, in four of the five patients with
      hypokalemia, and in two of the four patients with metabolic acidosis. Infusion
      related rigors were observed in four patients receiving amphotericin B
      deoxycholate and in one patient treated with ABCD. Reversible elevation of liver
      enzymes was found in one patient receiving ABCD. In this study ABCD proved less
      toxic than amphotericin B deoxycholate. The efficacy of ABCD alone cannot be
      assessed because of previous treatment with amphotericin B deoxycholate, but
      sequential treatment of deep Candida infections with amphotericin B deoxycholate
      and ABCD seems to be an effective therapeutic modality, especially in patients
      requiring prolonged administration of amphotericin B.

PMID- 9272386
TI  - Effect of clavulanic acid and/or polymorphonuclear neutrophils on amoxicillin
      bactericidal activity against Streptococcus pneumoniae.
AB  - The effects of polymorphonuclear neutrophils (PMNs) and/or clavulanic acid on the
      bactericidal activity of amoxicillin (at human serum achievable concentrations)
      against a serotype 3 penicillin-susceptible Streptococcus pneumoniae strain
      [minimal inhibitory concentration/minimal bactericidal concentration (MIC/MBC)
      values of penicillin, amoxicillin, and amoxicillin/clavulanic acid (2:1) =
      0.01/0.01 microgram/ml] and a serotype 9 penicillin-resistant strain [MIC/MBC of
      penicillin, amoxicillin, and amoxicillin/clavulanic acid (2:1) = 1/2
      microgram/ml] were studied. Against the penicillin-resistant strain,
      subinhibitory concentrations of amoxicillin reduced the growth rate; this effect
      was increased by the addition of clavulanic acid. A reduction of the penicillin
      resistant initial inocula (3 x 10(6) cfu/ml) at subinhibitory concentrations was
      obtained only with amoxicillin plus clavulanic acid and PMNs. At suprainhibitory
      concentrations, both clavulanic acid and PMNs increased the bactericidal activity
      of amoxicillin, as evidenced by an increased reduction in the penicillin
      resistant initial inocula. The combined effect of these antibiotics and immune
      defenses may help explain the maintenance of their clinical efficacy in
      respiratory tract infections, despite the increase in the incidence of penicillin
      resistant pneumococci.

PMID- 9272387
TI  - Relationship between hydrogen peroxide-producing strains of lactobacilli and
      vaginosis-associated bacterial species in pregnant women.
AB  - This study was conducted to determine the relationship between lactobacilli and
      bacterial species associated with bacterial vaginosis in pregnancy and the
      prevalence of H2O2-producing and non-producing strains of lactobacilli in
      pregnant women whose vaginal flora had already been analysed. Information was
      available for 174 pregnant women whose vaginal flora had been evaluated
      previously by examining gram-stained vaginal smears: 50 had grade III flora
      (bacterial vaginosis). 50 grade II flora, 41 flora graded as abnormal which then
      reverted to grade I (revertants) and 33 normal flora (controls). Lactobacilli
      were isolated from 19 of 50 women whose vaginal flora was grossly abnormal
      culturally and categorised as grade III by Gram staining. In 6 of these 50 women
      lactobacilli were isolated in large numbers, i.e. 10(5)-10(6) cfu/ml. H2O2
      producing strains of lactobacilli were isolated from 11 of 12 women with grade
      III flora who were randomly selected from this group. Thus, in those 11 women it
      appears that H2O2-producing lactobacilli had not protected them from developing
      bacterial vaginosis. Bacterial species associated with vaginosis were isolated in
      high numbers from a large proportion of women in the revertant and grade II
      groups in association with high counts of lactobacilli. Thus, in some women it is
      possible that a change to an abnormal flora could occur before the complete
      disappearance of lactobacilli. It is concluded that bacterial vaginosis may
      develop in some women despite the presence of H2O2-producing strains of
      lactobacilli and that other factors, as yet unidentified, might be conducive to
      the appearance of abnormal bacterial flora with progression to vaginosis.

PMID- 9272388
TI  - Molecular epidemiology of an outbreak due to extended-spectrum beta-lactamase
      producing enterobacteria in a French hospital.
AB  - Between June 1992 and June 1993, 128 extended-spectrum beta-lactamase-producing
      enterobacteria (123 Klebsiella pneumoniae, 3 Escherichia coli, 1 Enterobacter
      aerogenes, and 1 Citrobacter diversus) were collected in a French university
      hospital. These isolates were recovered mainly from patients hospitalized in
      intensive care and neurosurgery units. The 128 strains were divided into 14
      antibiotypes (ATBs; ATB1 to ATB14); 102 of 103 nonredundant isolates were shown
      to produce an SHV-4-related extended-spectrum beta-lactamase (pl 7.8,
      hybridization with a blaSHV probe); the remaining strain (Kp 2108) produced a TEM
      3-related extended-spectrum beta-lactamase (pl 6.3, hybridization with a blaTEM
      probe). For representative isolates, five plasmid profiles (Pl to Pll-4), eight
      ribotypes (E1 to E8), and seven arbitrarily primed polymerase chain reaction
      profiles (A1 to A7) were obtained. The results suggest the spread of an epidemic
      strain of Klebsiella pneumoniae (E1, A1, Pl, various ATBs) from an intensive care
      unit throughout the hospital. Another epidemic strain (E2, A2, pl, ATB4) was
      confined to the neurosurgery unit. Other extended-spectrum beta-lactamase
      producing Klebsiella pneumoniae of ribotypes distinct from E1 or E2 might result
      from the spread of an epidemic plasmid, such as reported for isolates of other
      enterobacterial species. Conversely, they might represent imported cases, such as
      the strain Kp 2108, which produced a TEM-3-related beta-lactamase.

PMID- 9272384
TI  - Current knowledge of Bartonella species.
AB  - Bartonella species are now considered emerging pathogens. Of the 11 currently
      recognized species, four have been implicated in human disease, although only two
      have been encountered in Europe. Bartonella quintana infections are now being
      diagnosed among the urban homeless and deprived, manifesting as trench fever, and
      Bartonella henselae has been shown to be the causative agent of cat scratch
      disease. Both species also cause a variety of HIV-associated infections,
      including bacillary anglomatosis. However, perhaps the most significant
      presentation of bartonellae infection is culture-negative endocarditis. The
      epidemiologies of Bartonella infections are poorly understood; most Bartonella
      henselae infections are probably acquired from infected cats, either directly by
      contact with a cat or indirectly via fleas. No animal reservoir has been
      implicated for Bartonella quintana; however, infection can be transmitted via the
      human body louse. Diagnosis of Bartonella infections can be made using
      histological or microbiological methods. The demonstration of specific antibodies
      may be useful in some instances, although certainly not in all. Cultivation of
      Bartonella is difficult, as the bacteria are extremely fastidious. Polymerase
      chain reaction-based or immunological methods for the detection of bartonella in
      infected tissues have proven useful. Clinical relapse is often associated with
      Bartonella infections despite a wide range of prescribed regimens. Only
      aminoglycosides display in vitro bactericidal activity against intracellular
      Bartonella species; therefore, they are recommended for treatment of Bartonella
      infections.

PMID- 9272389
TI  - Influence of a proton pump inhibitor-based therapy on Helicobacter pylori strain
      selection.
AB  - The influence of the proton pump inhibitor lansoprazole on strain diversity in
      Helicobacter pylori infected patients was investigated. Multiple isolates of
      Helicobacter pylori obtained pre- and post-therapy from gastric antral and body
      biopsies in 22 patients were compared using the random amplified polymorphic DNA
      polymerase chain reaction (RAPD-PCR) for analysis. Post-therapy strains
      exhibiting novel RAPD-profiles were found in 5 of 22 patients (4 of 11 patients
      treated with lansoprazole alone and 1 of 11 patients treated with lansoprazole
      plus amoxicillin). Proton pump inhibition may affect the microecology of the
      stomach by influencing the colonisation patterns of specific strains.

PMID- 9272390
TI  - Bacteremia caused by Leuconostoc cremoris in a patient with severe burn injuries.
AB  - A case of Leuconostoc cremoris bacteremia in a patient with burn wounds over 45%
      of the body surface is presented. Leuconostoc bacteremia has not previously been
      reported in burn patients. The predisposing factors in this case were severe burn
      wounds resulting in immunocompromise, presence of both intravenous and enteral
      feeding catheters, several surgical interventions and previous treatment with
      imipenem plus amikacin. The patient was successfully treated with ampicillin 2 g
      l.v. every 6 hours for 21 days. Infection with Leuconostoc should be suspected
      when vancomycin-resistant organisms resembling streptococci are isolated.

PMID- 9272391
TI  - Effect of different combinations of sparfloxacin, oxacillin, and fosfomycin
      against methicillin-resistant staphylococci.
AB  - The in vitro activity of combinations of sparfloxacin/oxacillin,
      sparfloxacin/fosfomycin, and oxacillin/fosfomycin was investigated against 16
      methicillin-resistant Staphylococcus aureus (MRSA) isolates and 12 methicillin
      resistant Staphylococcus epidermidis (MRSE) isolates moderately resistant to
      sparfloxacin. Synergic interactions were observed more frequently against MRSE
      than against MRSA strains. The most effective combination on both species was
      fosfomycin plus oxacillin, synergistic against ten of 16 MRSA and eight of 12
      MRSE strains.

PMID- 9272393
TI  - Pulsed-field gel electrophoresis analysis of clonal relationships among Neisseria
      meningitidis A strains from different outbreaks.
AB  - Pulsed-field gel electrophoresis was used to analyze the DNA of 67 Neisseria
      meningitidis A strains from five African outbreaks occurring between 1988 and
      1996. Endonuclease Bg/II was used to cut chromosomal DNA, generating 19
      analyzable fragments. This technique allowed comparison of clonal relationships
      between outbreak strains and revealed that the same pulsotype was responsible for
      the outbreaks. This pulsotype is closely related to strain B54, subgroup III
      reference strain, Finland, 1975, showing only two fragment differences.

PMID- 9272392
TI  - Susceptibility testing quality control studies with fosfomycin tromethamine.
AB  - Multiple studies were performed to define the quality control ranges for
      susceptibility tests of fosfomycin tromethamine. For disk diffusion tests, the
      limits proposed are 22 to 30 mm for Escherichia coli ATCC 25922 and 25 to 33 mm
      for Staphylococcus aureus ATCC 25923. Broth microdilution tests were not
      reproducible. For agar dilution tests, ranges proposed are 0.5 to 2.0
      micrograms/ml for Escherichia coli ATCC 25922, 0.5 to 4.0 micrograms/ml for
      Staphylococcus aureus ATCC 29213; 2.0 to 8.0 micrograms/ml for Pseudomonas
      aeruginosa ATCC 27853, and 32 to 128 micrograms/ml for Enterococcus faecalis ATCC
      29212.

PMID- 9272394
TI  - A case of fatal disseminated histoplasmosis of autochthonous origin in an Italian
      AIDS patient.

PMID- 9272395
TI  - Pneumonia caused by Micrococcus species in a neutropenic patient with acute
      leukemia.

PMID- 9272396
TI  - Transmission of multidrug-resistant strains of Mycobacterium tuberculosis in a
      high incidence community.

PMID- 9272397
TI  - Detection of Mycobacterium avium-intracellulare in the blood of HIV-infected
      patients by a commercial polymerase chain reaction kit.

PMID- 9272398
TI  - Edwardsiella tarda septicemia with cellulitis in a patient with AIDS.

PMID- 9272399
TI  - Nonserotypeable Shigella dysenteriae isolated from a Dutch patient returning from
      India.

PMID- 9272400
TI  - Study of the use of vitamin K in neonates in France.
AB  - OBJECTIVE: Because of the risk of haemorrhagic disease of the newborn as a result
      of a deficit in vitamin K, it is generally agreed that newborns should receive
      vitamin K. However, there is no consensus concerning the route of administration,
      dose, number of doses, or dose frequency. METHODS: We studied patterns of vitamin
      K administration in all maternity hospitals in France in order to establish the
      range of practices and policies. Six hundred and forty questionnaires were
      analysed. Vitamin K was given systematically to all neonates in 619 maternity
      hospitals (96.7%), not given to any neonates in 2 (0.3%), and only to certain
      newborns in 19 (3%). A similar protocol was used for all newborns in 299 (47%) of
      the maternity hospitals, and the treatment protocol differed according to the
      neonatal clinical picture in 336 maternity hospitals (53%). RESULTS: The route of
      administration agreed with the recommendation that healthy newborns receive
      formula milk. In contrast, infants receiving breast milk were given IM vitamin K
      in only 19% of the maternity hospitals studied and regular weekly doses were
      prescribed in only 56%. In premature infants, IM doses were prescribed in only
      46% of cases and repeat weekly doses in 34%. The dose generally prescribed (5 mg
      p.o. or IM) was not the recommended dose.

PMID- 9272401
TI  - A comparative study of the effects of yohimbine and anetholtrithione on salivary
      secretion in depressed patients treated with psychotropic drugs.
AB  - OBJECTIVE: The present study compares the effects of yohimbine, an alpha 2
      adrenoceptor antagonist, and anetholtrithione, a reference drug in the treatment
      of dry mouth, in patients treated with psychotropic drugs (tricyclic
      antidepressants or neuroleptics) and suffering from xerostomia. METHODS: Ten
      patients were included in a randomized, double-blind, cross-over study, and
      receiving after yohimbine (3 x 6 mg per day) or anetholtrithione (3 x 25 mg per
      day) orally for 5 days. Salivary secretion was estimated under resting
      conditions, before any drug, and then on day 6, 1 h after the ingestion of
      yohimbine or anetholtrithione. RESULTS: Compared with basal secretion, the
      increase in salivary flow was significantly more marked after yohimbine than
      after anetholtrithione. CONCLUSION: This study demonstrates the sialogenic effect
      of yohimbine in drug-induced dry mouth.

PMID- 9272402
TI  - Salt enhances responsiveness of terminal aortic vascular bed to sympathetic
      activity.
AB  - OBJECTIVE: Haemodynamic and laboratory examinations were performed in 27
      essential hypertensives. The participation of the sympathetic system was
      estimated from the percentage decrease in regional vascular resistance caused by
      1 mg prazosin, during varied salt intake (50-80 mEq sodium per day for 9 weeks,
      followed by 220-250 mEq sodium per day for 10 days), with or without benidipine.
      RESULTS: During low salt intake, terminal aortic and renal resistances were
      decreased by prazosin, but superior mesenteric resistance remained unchanged. In
      the saltsensitive patients, whose mean arterial pressure increased more than 5
      mmHg with salt repletion, salt loading increased superior mesenteric and renal
      resistances but did not change terminal aortic resistance. This salt-induced
      vasoconstriction of renal and superior mesenteric arteries is not related to an
      increase in sympathetic activity, because both plasma noradrenaline
      concentrations and the percentage decrease in these regional vascular resistances
      by prazosin remained unchanged after salt loading. On the other hand, terminal
      aortic area demonstrated an increase in responsiveness to noradrenaline
      (increased response to prazosin) with salt loading in spite of unchanged terminal
      aortic resistance. This salt-induced increase in sympathetic responsiveness in
      the terminal aortic area was inhibited with the addition of benidipine, which
      abolished development of salt-induced hypertension and its accompanying
      haemodynamic responses.

PMID- 9272403
TI  - Moxonidine and cognitive function: interactions with moclobemide and lorazepam.
AB  - OBJECTIVE: Moxonidine represents a new generation of centrally acting
      antihypertensive drugs. It binds to I1-imidazoline receptors and exerts its
      antihypertensive activity through a reduction in systemic vascular resistance,
      while cardiac output remains unchanged or even increases slightly. Moxonidine is
      prescribed for the treatment of mild to moderate hypertension. Typical doses are
      0.4 to 2.0 mg given as one dose in the morning or as divided doses in the morning
      and evening. METHODS: The effects of moxonidine 0.4 mg once daily in combination
      with moclobemide or lorazepam were investigated in two, double-blind, randomised,
      placebo-controlled, two-way crossover studies in a total of 48 healthy
      volunteers. Safety assessments were made in each study and included pre- and post
      study measurement of blood pressure, heart rate, ECG, haematology, blood
      biochemistry, and urinalysis, and recording of adverse events. RESULTS: In the
      first study, moxonidine alone was found to produce small but statistically
      significant impairments of vigilance detection speed at 4 h and 6 h. Lowering of
      subjective alertness was also observed. Repeat dosing with moxonidine produced an
      impairment of memory scanning performance. These findings were not reproduced in
      the second study, in which moxonidine alone produced an improvement in immediate
      word recall at 4 h and 6 h. No interactions were observed when moxonidine was co
      administered with moclobemide. Moxonidine, when co-administered with lorazepam,
      produced interactions with three tasks requiring high levels of attention:
      choice, simple reaction time and digit vigilance performance; memory tasks;
      immediate word recall, delayed word recall accuracy; and visual tracking. A total
      of 47 adverse events were reported in study 1. Moxonidine produced a slight
      decrease of systolic and diastolic blood pressure. In study 2, a total of 55
      adverse events were reported. In both trials, the most frequently reported events
      were tiredness and dryness of mouth, the latter occurring only under the
      moxonidine treatment. There were no clinically relevant changes observed in blood
      pressure, pulse rate, and laboratory tests in either study, nor was there any
      evidence of any interaction between moxonidine and either moclobemide or
      lorazepam. CONCLUSION: Moxonidine was found to be safe and well tolerated in
      healthy volunteers. However, the impairments on attentional tasks were greater
      when moxonidine was co-administered with lorazepam 1 mg. These effects should be
      considered when moxonidine is codosed with lorazepam, although they were smaller
      than would have been produced by a single dose of lorazepam 2 mg.

PMID- 9272405
TI  - The clinical pharmacology of single doses of otilonium bromide in healthy
      volunteers.
AB  - OBJECTIVE: Otilonium is a smooth muscle spasmolytic with greater affinity for
      receptors in the smooth muscle of distal than proximal gut in rats. This study
      was the first to compare distal and proximal GI transit effects in human
      subjects. METHODS: Using an increasing dose design for the safe exploration of
      clinical and supraclinical single dose levels, two groups of eight volunteers
      received either 40, 120 and 200 mg or 80, 160 and 240 mg otilonium. Gastric
      emptying of 400 ml 10% glucose solution was assessed by epigastric impedance
      (EI), orocaecal transit time (OCTT) by the lactulose breath-hydrogen method and
      whole gut transit time (WGTT) by the method of Hinton et al. [1]. Potential
      anticholinergic effects were assessed via visual accommodation using the RAF rule
      and saliva flow in response to sucking a sweet. RESULTS: Median WGTT after 120 mg
      significantly increased by 4.1 h relative to placebo, but at higher doses median
      changes relative to placebo were not significant due to wide increases in group
      variance. The EI t50% was delayed by 1.4 min when results from the two highest
      doses were combined and compared with placebo; this small difference was
      statistically significant but seems unlikely to achieve physiological or clinical
      significance. OCTT, visual accommodation and saliva flow were unaltered.
      Otilonium bromide was well tolerated at all doses, due mainly to low systemic
      absorption.

PMID- 9272404
TI  - The negative mucosal potential: separating central and peripheral effects of
      NSAIDs in man.
AB  - OBJECTIVE: We wanted to test whether assessment of both a central pain-related
      signal (chemo-somatosensory evoked potential, CSSEP) and a concomitantly recorded
      peripheral signal (negative mucosal potential, NMP) allows for separation of
      central and peripheral effects of NSAIDs. For this purpose, experimental
      conditions were created in which NSAIDs had previously been observed to produce
      effects on phasic and tonic pain by either central or peripheral mechanisms.
      METHODS: According to a double-blind, randomised, controlled, threefold cross
      over design, 18 healthy subjects (11 males, 7 females; mean age 26 years)
      received either placebo, 400 mg ibuprofen, or 800 mg ibuprofen. Phasic pain was
      applied by means of short pulses of CO2 to the nasal mucosa (stimulus duration
      500 ms, interval approximately 60 s), and tonic pain was induced in the nasal
      cavity by means of dry air of controlled temperature, humidity and flow rate (22
      degrees C, 0% relative humidity, 145 ml.s-1). Both CSSEPs as central and NMPs as
      peripheral correlates of pain were obtained in response to the CO2 stimuli.
      Additionally, the subjects rated the intensity of both phasic and tonic pain by
      means of visual analogue scales. RESULTS: As described earlier, administration of
      ibuprofen was followed by a decrease in tonic pain but-relative to placebo-an
      increase in correlates of phasic pain, indicating a specific effect of ibuprofen
      on the interaction between the pain stimuli under these special experimental
      conditions. Based on the similar behaviour of CSSEP and NMP, it was concluded
      that the pharmacological process underlying this phenomenon was localised in the
      periphery. By means of the simultaneous recording of interrelated peripheral and
      central electrophysiologic correlates of nociception, it was possible to separate
      central and peripheral effects of an NSAID. The major advantage of this pain
      model is the possibility of obtaining peripheral pain-related activity directly
      using a non-invasive technique in humans.

PMID- 9272406
TI  - Pharmacokinetic and pharmacodynamic interaction of single oral doses of valsartan
      and furosemide.
AB  - OBJECTIVE: Pharmacokinetic and pharmacodynamic interactions between single oral
      doses of valsartan (160 mg) and furosemide (40 mg) were investigated in an open,
      randomized, three-period crossover study in twelve healthy male subjects.
      METHODS: A washout period of one week was observed between treatments.
      Pharmacokinetic measurements included plasma concentrations of valsartan and
      furosemide, and urinary excretion of the latter. Plasma renin activity (PRA),
      plasma angiotensin II, blood pressure, heart rate, as well as urinary water and
      electrolyte excretion were determined as pharmacodynamic variables. Efficiency of
      furosemide for sodium and water excretion was calculated as the ratio of the
      measured pharmacodynamic effect and the urinary excretion of furosemide. RESULTS:
      Simultaneous administration of valsartan and furosemide did not modify the
      pharmacokinetics of valsartan. In contrast, Cmax, AUC, and urinary excretion of
      furosemide were significantly reduced following simultaneous treatment with
      valsartan. Inter- and intra-individual variability of the pharmacokinetic
      variables was high for both furosemide and valsartan. PRA and angiotensin II
      increased, and blood pressure decreased after all treatments. These effects were
      most pronounced after the combined treatment. The decrease in blood pressure was
      additive, at most, while the increase in PRA and angiotensin II appeared to
      exceed simple addition. No relevant effects on heart rate were observed. The
      diuretic effect of furosemide, as assessed by urinary water and electrolyte
      excretion, was unchanged after co-administration of valsartan, despite the lower
      bioavailability of furosemide after the combined treatment.

PMID- 9272407
TI  - Transdermal nitroglycerin: clinical and pharmacokinetic consequences of renewing
      the patch and the application site.
AB  - OBJECTIVE: We examined whether nitroglycerin (glyceryl trinitrate, GTN) patch
      treatment for 24 h could induce local cutaneous changes that impaired drug
      delivery and clinical efficacy. METHODS: Twenty angina patients were exercise
      tested after 2 and 24 h of treatment and then 2 h after patch renewal. The patch
      was either renewed on a new skin location or on the previous application site in
      a randomised, double-blind, cross-over protocol. GTN plasma concentrations and
      finger plethysmography were obtained before and after each exercise test. RESULTS
      AND CONCLUSIONS: The clinical efficacy, the effect seen on plethysmography and
      the GTN plasma concentrations tended to increase after patch renewal, regardless
      of the application site of the renewed patch. Hence, cutaneous changes of
      clinical importance could not be demonstrated.

PMID- 9272408
TI  - Ketotifen pharmacokinetics in children with atopic perennial asthma.
AB  - OBJECTIVE: Published pharmacokinetic data on ketotifen are sparse, although it is
      a commonly used prophylactic agent in various allergic disorders in adults and
      children. The aim of this study was to assess the steady-state pharmacokinetics
      of ketotifen in children with atopic perennial asthma who were participating in a
      clinical trial. METHOD: The NONMEM population approach with sparse sampling was
      utilized. The data set consisted of 239 samples from 48 children who were
      randomized to receive either 1 mg or 2 mg oral ketotifen daily. Patients
      underwent a clinical examination and had a blood sample taken at 2-week intervals
      for 12 weeks. The ketotifen concentrations were measured by RIA. RESULTS: A one
      compartment model with first-order absorption was fit to the data. Volume was
      estimated at 394 l and clearance (CL) at 97.4 l.h-1 (3.6 l.h-1.kg-1). Weight or
      body surface area were the most influential covariates for explaining
      interindividual variability in CL. The 2-mg dose appeared to have a relative bio
      availability of 85% of the 1-mg dose. CONCLUSION: Children have a faster
      clearance of ketotifen than adults and would therefore require a higher dose per
      kilogram body weight to give comparable steady-state levels.

PMID- 9272409
TI  - Non-response to maprotiline caused by ultra-rapid metabolism that is different
      from CYP2D6?
AB  - CASE: We are reporting about a patient with major depression who failed to
      respond to pharmacotherapy due to ultra-rapid metabolism of maprotiline. Under
      daily oral doses of 175 mg maprotiline, the patient's metabolic ratio (MR) for
      maprotiline in plasma was 9.2 (expected MRp: 2.4) and the clearance of
      maprotiline (CLM) was 4190 ml.min-1 (expected CLM = 1220 in extensive
      metabolisers of CYP2D6). RESULTS: The patient's MRurine for sparteine was 0.5,
      which is within the range for extensive metabolisers of CYP2D6. Genotyping did
      not show a duplication of the CYP2D6L allele. The patient's caffeine half-life
      was 10 h, thus, precluding ultra-rapid metabolism for CYP1A2. The therapeutic
      regiment was changed to co-administration of 200 mg maprotiline and 20 mg
      fluoxetine once per day in order to inhibit metabolism via CYP2D6. Subsequently,
      MRP of maprotiline (4.9) and CLM were reduced (1900 ml.min-1; expected CLM in
      poor metabolisers: of CYP2D6 364). This regimen improved the clinical outcome of
      the underlying disease. CONCLUSION: We conclude that for the non-response seen
      with maprotiline, P450 isozymes other than CYP2D6 or CYP1A2 are responsible. As
      CYP2C19 is involved in the metabolism of a number of tricyclic antidepressants it
      may be a candidate for ultra-rapid metabolism in this patient.

PMID- 9272410
TI  - Genetic polymorphism of CYP2C19 and lansoprazole pharmacokinetics in Japanese
      subjects.
AB  - OBJECTIVE: We investigated whether interindividual differences in the
      pharmacokinetic disposition of lansoprazole are attributed to the genetic
      polymorphism of CYP2C19 which occurred by two mutations. CYP2C19m1 and CYP2C19m2,
      in 20 Japanese subjects. METHODS: Polymerase chain reaction (PCR) restriction
      fragment length polymorphism procedures were used to detect the CYP2C19m1
      mutation in exon 5 and the CYP2C19m2 mutation in exon 4 using SmaI and BamHI,
      respectively. RESULTS: Ten subjects were homozygous (wt/wt subjects) for the wt
      allele in both exon 5 and exon 4, four subjects were heterozygous (wt/m1) for the
      CYP2C19m1 mutation, and two subjects were heterozygous (wt/m2) for the CYP2C19m2.
      The remaining four subjects had both mutated alleles in CYP2C19 genes, i.e., two
      were homozygous (m1/m1) for the defect in exon 5 and two were heterozygous
      (m1/m2) for the two defects in exons 5 and 4. The subjects in group 1 (wt/wt,
      wt/m1 and wt/m2) were the extensive metabolizers (EMs) for 5-hydroxylation of
      lansoprazole and were in the range of hydroxylation indexes from 3.83 to 19.8,
      whereas the subjects in group 2 (m1/m1 and m1/m2) were the poor metabolizers
      (PMs) and the indexes were in the range of 38.5 to 47.6. In group 2, AUC, t1/2
      and CL/f of lansoprazole were significantly greater, longer, and lower,
      respectively, than those in group 1.

PMID- 9272411
TI  - Comparison of pharmacokinetics and dynamics of two dosage regimens of foscarnet
      in AIDS patients with Cytomegalovirus retinitis.
AB  - OBJECTIVE: To compare the pharmacokinetics of foscarnet administered as an
      infusion twice daily (BID) or thrice daily (TID), and to compare the effects on
      the electrolyte balance, cardiac and renal functions over a 3-week induction
      treatment of Cytomegalovirus (CMV) retinitis. METHODS: Pharmacokinetics/dynamics
      of foscarnet were investigated on treatment days 1, 14 and 21. Twelve AIDS
      patients with CMV retinitis completed the investigation period. Concentrations of
      foscarnet and electrolytes were assayed by high-performance liquid chromatography
      (HPLC) and by an ion-selective analyser, respectively. RESULTS: The
      pharmacokinetics of the two regimens were essentially similar. Foscarnet plasma
      and creatinine clearances were 2.0 and 1.6 ml.min-1.kg-1, respectively, in the
      BID group at steady state (day 21). In the TID group the corresponding values
      were 1.8 and 1.7 ml.min-1.kg-1, respectively. In both regimens the elimination
      half-life of foscarnet was 2-3 h. Ionized calcium concentrations were transiently
      decreased and strongly inversely correlated to foscarnet plasma concentrations in
      both regimens with no significant differences between groups. A trend towards
      prolongation of the QTc interval was seen when data from both treatments were
      analysed together. CONCLUSION: Our data suggest comparable pharmacokinetics of
      foscarnet after intermittent administration BID or TID during a 3-week induction
      period.

PMID- 9272413
TI  - Pharmacokinetics of cloxacillin in patients undergoing hip or knee replacement.
AB  - OBJECTIVE: The pharmacokinetics of cloxacillin was investigated in 14 men and 24
      women undergoing cemented hip (n = 19; age range 56-90) or knee replacement
      surgery (n = 19; age range 51-84) for osteoarthritis. Cloaxacillin 1 g was given
      intravenously as a bolus dose at the induction of anesthesia, and plasma samples
      and urine were collected for 6 h. Drug levels were determined using HPLC.
      RESULTS: Preoperative serum creatinine levels were 84 mumol.l-1 in hip patients
      and 72 mumol.l-1 in knee patients. The calculated values for creatinine clearance
      were 63 and 85 ml.min-1.1.73 m-2, respectively. Total clearance of cloxacillin
      was 134 ml.min-1.1.73 m-2 in eighteen evaluated patients undergoing hip
      replacement, and 162 ml.min-1.1.73 m-2 in eighteen patients undergoing knee
      surgery. Renal clearance was 72 and 79 ml.min-1.1.73 m-2, respectively. Non-renal
      clearance was 57 ml.min-1.1.73 m-2 in hip patients and 77 ml.min-1.1.73 m-2 in
      knee patients. Renal clearance of cloxacillin correlated with the estimated
      creatinine clearance (r = 0.652). Although women received higher doses than men
      (median 2.02 vs 2.32 mmol.1.73 m-2), there were no sex differences in clearance
      corrected for body surface area. CONCLUSION: Total clearance of cloxacillin was
      lower in patients undergoing hip replacement than in patients undergoing
      replacement of the knee, but there was no difference between men and women.

PMID- 9272412
TI  - Itraconazole moderately increases serum concentrations of oxybutynin but does not
      affect those of the active metabolite.
AB  - OBJECTIVE: Oxybutynin has low oral bioavailability due to an extensive
      presystemic metabolism. It has been suggested that the biotransformation of
      oxybutynin is dependent on CYP3A. Because itraconazole, a widely used mycotic, is
      a potent inhibitor of CYP3A4, we wanted to study a possible interaction between
      oxybutynin and itraconazole. METHODS: In this double-blind, randomized, two-phase
      cross-over study, ten healthy volunteers received either 200 mg itraconazole or
      placebo for 4 days. On day 4, each volunteer ingested a single dose of 5 mg
      oxybutynin. Serum concentrations of oxybutynin, its active metabolite N
      desethyloxybutynin, and itraconazole were monitored over 24 h. RESULTS:
      Itraconazole significantly increased both the area under the serum drug
      concentration-time curve (AUC0-t) and the peak concentration of oxybutynin
      twofold. The AUC0-t and the peak concentration of N-desethyloxybutynin were not
      significantly affected by itraconazole. Itraconazole did not change the peak time
      or the elimination half-life of either oxybutynin or N-desethyloxybutynin. The
      occurrence of adverse events after oxybutynin administration was not increased by
      itraconazole. CONCLUSIONS: Itraconazole moderately increases serum concentrations
      of oxybutynin, probably by inhibiting the CYP3A-mediated metabolism. However, the
      concentrations of N-desethyloxybutynin were practically unchanged. Since about
      90% of the antimuscarinic activity of oxybutynin is attributable to N
      desethyloxybutynin, any interaction of oxybutynin with CYP3A4 inhibiting drugs
      has only minor clinical significance.

PMID- 9272414
TI  - A comparison of EMIT and FPIA methods for the detection of cyclosporin A blood
      levels: does impaired liver function make a difference?
AB  - OBJECTIVE: Apparent cyclosporin A (CSA) blood levels, as determined by
      fluorescence polarization immunoassay (FPIA) and enzyme-multiplied immunoassay
      technique (EMIT), were compared in CSA-treated patients with various degrees of
      liver dysfunction. METHODS: FPIA and EMIT were performed in parallel according to
      test manufacturer instructions in blood from kidney (n = 82), liver (n = 96) and
      heart transplant (n = 20) patients. RESULTS: The precision of both techniques was
      greatest in patients with the highest blood levels, and at each blood level
      greater for the FPIA than for the EMIT. Apparent CSA blood levels, as determined
      by EMIT, were typically approximately 70% of those determined by FPIA, indicating
      greater cross-reaction of the antibody in the FPIA with CSA metabolites. However,
      the ratio of values determined with EMIT and FPIA was very similar in kidney,
      liver and heart transplant patients. Among liver transplant patients it was also
      very similar in those without major alterations of hepatic function and in those
      with impaired excretory (increased bilirubin and gamma GT) or synthetic (i.e.,
      reduced thromboplastin time) function. Extended storage of blood samples for up
      to 10 days did not affect apparent CSA blood level estimates by EMIT in a
      clinically relevant manner. CONCLUSIONS: We conclude that the greater specificity
      of the antibody in the EMIT for the CSA parent compound does not translate into a
      clinically relevant advantage for CSA monitoring.

PMID- 9272415
TI  - Dextromethorphan O-demethylation polymorphism in the Uruguayan population.

PMID- 9272416
TI  - Is there any difference between daytime and nighttime debrisoquine metabolism?

PMID- 9272417
TI  - Immunohistochemical localization of basic fibroblast growth factor (bFGF) during
      folliculogenesis in the human ovary.
AB  - Basic fibroblast growth factor (bFGF) has been suggested to be one of the
      intraovarian regulators of ovarian folliculogenesis, but its localization in the
      human ovary remains to be determined. We examined the immunohistochemical
      reactivity for bFGF in the course of follicular development and corpora lutea
      formation in the human ovary. Pregranulosa cells in the primordial follicle were
      negative, but at the preantral stage both granulosa and theca cells showed weakly
      positive immunostaining for bFGF. In the antral follicles, both granulosa and
      theca interna cells showed stronger staining for bFGF with the increase in
      follicular diameter. In atretic follicles at various stages, granulosa cells were
      negative or weakly positive for bFGF, whereas luteinized theca cells showed
      strong immunoreactivity. In the corpora lutea during the early luteal phase,
      granulosa lutein cells were strongly positive for bFGF but in the late luteal
      phase became immunonegative. On the other hand, bFGF staining in theca lutein
      cells was strong throughout the course of corpora lutea formation and regression.
      These findings suggest that bFGF is localized not only in granulosa cells but
      also in theca cells, and in the latter, bFGF immunoreactivity is associated with
      luteinization.

PMID- 9272418
TI  - Effects of angiotensin converting enzyme inhibitor cilazapril and angiotensin II
      antagonist saralasin in ovarian hyperstimulation syndrome in the rabbit.
AB  - We investigated the possible effects of the angiotensin converting enzyme (ACE)
      inhibitor cilazapril and angiotensin II antagonist saralasin on ovulation,
      ovarian steroidogenesis and ascites formation in the ovarian hyperstimulation
      syndrome (OHSS) in the rabbit model. OHSS was induced in rabbits by human
      menopausal gonadotropin (hMG) and intermittent human chorionic gonadotropin
      (hCG). In the cilazapril group (n = 10), animals also received cilazapril 2 mg/kg
      intraperitoneally daily for 7 days. In the saralasin group (n = 8), animals
      received saralasin intraperitoneally 1 h before or 1 h after hCG administration.
      Control animals (n = 8), received intraperitoneal saline solution. Serial blood
      samples were drawn on days 1, 5, 7 and 9 to measure serum estradiol and
      progesterone levels. On day 9, all rabbits underwent surgical exploration.
      Peritoneal and pleural fluid formation, ovarian weights and number of ovulations
      were determined. The volume of the ascitic and pleural fluids after
      hyperstimulation were not statistically different between the control, cilazapril
      and saralasin groups. The weight gains and ovarian weights of animals were
      similar between treatment and control groups. Saralasin significantly (p < 0.05)
      inhibited ovulation, but cilazapril did not. Cilazapril and saralasin did not
      affect progesterone production. Only cilazapril significantly decreased estradiol
      production (p < 0.05). In conclusion, the ACE inhibitor cilazapril and
      angiotensin II antagonist saralasin did not prevent ascites formation in OHSS.
      The ovarian renin-angiotensin system may not be the only factor acting in ascites
      formation in the OHSS.

PMID- 9272419
TI  - In vivo effects of estrogens on c-erbB-2 oncoprotein levels in chorionic villous
      tissue and maternal serum.
AB  - The c-erbB-2-encoded oncoprotein p185 (HER2) is overexpressed in the fetal
      epithelium, the placenta and several carcinomas. Elevated serum levels of the
      released ectodomain (p105) were found in cancer patients and pregnant women at
      term. In cultured breast cancer cells estradiol inhibited p185 expression and
      induced growth arrest. These results prompted us to investigate the in vivo
      influence of serum estradiol and estriol on c-erbB-2 protein levels in pregnancy.
      We examined chorionic villous tissue extracts and maternal sera obtained from six
      legal abortions in the first trimester and 20 vaginal deliveries at term. For
      quantification of c-erbB-2 protein we employed an ELISA. In the first trimester
      maternal p105 serum levels were significantly (p < 0.0001) lower and p185 tissue
      levels significantly (p < 0.05) higher than in the third trimester. The highest
      p105 values were found in additionally examined cord blood. Interindividual
      regression analyses yielded inverse correlation between estradiol concentrations
      and placental p185 expression in the first (r = -0.58) and third trimester (r = 
      0.38) as well as p105 serum levels in the first trimester (r = -0.83). Estriol
      was correlated positively with p105 values in maternal and umbilical serum but
      not with placental p185 expression. We conclude that estradiol down-regulates
      p185 expression in pregnancy whereas the level of maternal p105 depends on the
      total amount of fetoplacental p185.

PMID- 9272420
TI  - Serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 levels in
      children with precocious puberty treated with gonadotropin-releasing hormone
      analog without or in combination with cyproterone acetate.
AB  - In order to assess the behavior of growth hormone, insulin-like growth factor-I
      (IGF-I) and IGF binding protein-3 (IGFBP-3) in girls with central precocious
      puberty treated with gonadotropin-releasing hormone (GnRH) analog-therapy, we
      studied 14 girls with this condition, the patients were subdivided into two
      groups, according to the therapy followed. Group A (n = 7; age 4.2-7.1 years)
      received GnRH analog in combination with cyproterone acetate, and Group B (n = 7;
      age 4.4-6.9 years) received long-acting analog alone. Before treatment, IGF-I
      levels were significantly increased compared to healthy age-matched children in
      the two groups (447 +/- 33 micrograms/l for Group A and 435 +/- 38 micrograms/l
      for Group B vs. control 175 +/- 78 micrograms/l; p < 0.01). Moreover, serum IGFBP
      3 levels were significantly higher than the age-related reference range for IGFBP
      3 (4478.2 +/- 178 micrograms/l for Group A and 4532.3 +/- 167 micrograms/l for
      Group B vs. control 2905 +/- 641 micrograms/l; p < 0.01). During the two years of
      gonadal suppression, Group A patients showed a significant decrease in IGF-I and
      IGFBP-3 levels, while in Group B there was no significant change in IGF-I;
      moreover, in Group B, IGFBP-3 levels increased significantly compared to baseline
      values during the first year of treatment (4532.3 +/- 167 micrograms/l vs. 5410.3
      +/- 169 micrograms/l; p < 0.05) and decreased significantly at the end of the
      second year of treatment (3816.1 +/- 189 micrograms/l vs. 5410.3 +/- 169
      micrograms/l; p < 0.01). Our study shows that the two different treatments of
      precocious puberty (with and without cyproterone acetate) have different effects
      on IGF-I and IGFBP-3, and suggests that these growth factors are under different
      metabolic regulation.

PMID- 9272421
TI  - Treatment of hirsutism by finasteride and flutamide in women with polycystic
      ovary syndrome.
AB  - Forty-four hirsute patients with polycystic ovary syndrome were randomly treated
      with finasteride (5 mg daily) or flutamide (250 mg twice daily) for 6 consecutive
      months. Hirsutism was evaluated before and after therapy with the Ferriman
      Gallwey score and with measurement of hair diameter (micron). The hairs were
      taken from four different body areas: the face, abdomen, thighs and forearm. The
      measurement was carried out with a micrometer applied to the optical microscope.
      Mean plasma concentrations of luteinizing hormone, follicle-stimulating hormone,
      17 alpha-hydroxyprogesterone, androstenedione, testosterone, free testosterone,
      dehydroepiandrosterone sulfate, insulin, and sex hormone binding globulin were
      determined before and after therapy. Hematochemical examinations and side-effects
      were controlled after the treatment. After 6-months' therapy, both antiandrogens
      significantly reduced the Ferriman-Gallwey score and hair diameter in all the
      body areas. Finasteride reduced the Ferriman-Gallwey score by 25% and hair
      diameter by 16-25%; flutamide reduced the score by 20% and hair diameter by 15.3
      22%. Abdominal hairs were more sensitive to both drugs. Flutamide induced a
      significant drop in total testosterone and dehydroepiandrosterone sulfate. No
      important side-effect or change in the hematochemical parameters was observed.
      Our data demonstrate that finasteride and flutamide are effective in the
      treatment of hirsutism in patients with polycystic ovary syndrome.

PMID- 9272422
TI  - The outcome of an in vitro fertilization program in women with polycystic ovary
      syndrome.
AB  - The objective of this study was to examine the efficacy of D-triptorelin in the
      long protocol and follicle-stimulating hormone (FSH) in an IVF-embryo transfer
      program in a group of patients with polycystic ovary syndrome (PCOS) who had
      earlier failed to respond or did not conceive after clomiphene citrate (CC)/human
      menopausal gonadotropin (hMG) or 'flare up' gonadotropin-releasing hormone
      agonist (GnRHa)/hMG stimulation. Eighty-nine women with PCOS (based on typical
      ultrasound criteria) had 1-3 treatment cycles without success. The stimulation
      protocol was changed to D-triptorelin given in midluteal phase and when pituitary
      desensitization was achieved, FSH administration was started. The clinical
      pregnancy rate per transfer in this 'negatively selected' group of PCOS patients
      was 29%. This was the same as the rate for a group of women with tubal factor, as
      was the spontaneous miscarriage rate. Although the use of GnRH agonists in the
      long protocol increases the costs of treatment, the number of cancelled cycles is
      reduced. The pregnancy rate increased in this group of women with PCOS.

PMID- 9272423
TI  - Expression of vascular endothelial growth factor in human luteinizing granulosa
      cells and its correlation with the response to controlled ovarian
      hyperstimulation.
AB  - Ovulation induction represents one of the most important steps for the success of
      assisted reproductive technology (ART) procedures. To better understand the
      mechanisms that regulate follicle growth, oocyte maturation, and ovarian
      steroidogenesis, we investigated the correlations between vascular endothelial
      growth factor (VEGF) gene expression in human luteinizing granulosa cells,
      steroid production and oocyte retrieval in patients undergoing controlled ovarian
      hyperstimulation. We evaluated the messenger ribonucleic acid (mRNA) for VEGF in
      human luteinizing granulosa cells obtained at the time of oocyte retrieval from
      24 women participating in an in vitro fertilization program at the Reproductive
      Endocrinology Center of our Department of Obstetrics and Gynecology. We found a
      positive linear correlation of VEGF mRNA with estradiol and progesterone serum
      levels at the day of oocyte retrieval (p < 0.05). Furthermore, VEGF mRNA
      expression was significantly higher in granulosa cells obtained from patients
      with an elevated number of oocytes and high fertilization rate (p < 0.05). Our
      data confirm that VEGF may play an important role in the regulation of vascular
      development during follicular growth and luteal differentiation.

PMID- 9272424
TI  - Do changes in growth hormone levels correlate with IGF-I levels in patients
      undergoing IVF-ET?
AB  - It has been suggested that adjunctive growth hormone (GH) therapy improves
      ovarian response and in vitro fertilization (IVF) outcome in specific groups of
      patients. The correlation between insulin-like growth factor (IGF) and GH is well
      established. The aim of this study was to determine whether changes in plasma GH
      correlate with IGF blood levels in patients during IVF treatment. Thirty-six
      women undergoing IVF and embryo transfer (ET) were examined. Ovarian stimulation
      was carried out by gonadotropin-releasing hormone agonists (GnRHa) and
      gonadotropins. Blood was drawn at the early and late follicular phase, on the day
      of human chorionic gonadotropin (hCG) injection and at the mid- and the late
      luteal phases. The samples were assayed for IGF-I, IGF-II, IGF-binding protein-3
      (IGF BP-3), GH and estradiol. According to the IGF-I and GH plasma levels,
      patients were divided into three major groups: Group I consisted of patients in
      whom peak levels of GH reached more than 4 ng/ml and IGF-I decreased
      significantly. In this group, estradiol levels were 1863 +/- 149 pg/ml. Group II
      consisted of patients in whom peak blood GH levels did not exceed 2.5 ng/ml and
      the IGF-I level remained unchanged. In this group estradiol levels were 630 +/-
      57 pg/ml. Group III consisted of patients in whom blood GH levels were low and
      remained unchanged while estradiol levels were 1600 +/- 420 pg/ml. In this group
      no significant increase in IGF-levels were observed. There was no significant
      change in the levels of either IGF-II or IGF BP-3 in any of the groups. We can
      conclude that (1) there is a negative correlation between GH and IGF-I plasma
      levels in patients undergoing controlled ovarian hyperstimulation (COH)-IVF, when
      levels of estradiol and GH are elevated; (2) plasma levels of IGF-I under ovarian
      hyperstimulation are probably regulated by a multifactorial system; and (3) no
      correlation was found between the plasma levels of IGF-I and those of IGF-II and
      IGF BP-3 in all patient groups.

PMID- 9272425
TI  - Changes in prolactin levels with the menopause: the effects of estrogen/androgen
      and calcitonin treatment.
AB  - Prolactin levels were evaluated over a 2-year period in three groups of
      postmenopausal women: group A consisted of 35 untreated women distributed
      according to time since the menopause; group B consisted of 17 women on a
      combined estrogen/androgen preparation (Gynodian depot) intramuscularly at
      monthly intervals; and group C consisted of 12 women on 100 units of salmon
      calcitonin intranasally on alternate days and 1500 mg calcium daily. The control
      group (group D) consisted of 11 healthy premenopausal women. Serum prolactin,
      estradiol, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels
      were measured at the onset and at 6-month intervals over 24 months. Mean serum
      prolactin concentrations decreased significantly during the second postmenopausal
      year in untreated women p = 0.0001 and p = 0.0000 after 18 and 24 months,
      respectively) when compared to either the levels in premenopausal women or those
      at the beginning of the menopause (p = 0.0007). Neither combined
      estrogen/androgen nor calcitonin therapy significantly influenced prolactin
      levels which were similar throughout the observed period. In the group on a
      combined estrogen/androgen preparation, physiological estradiol concentrations
      together with a suppression of gonadotropins during the first 6 months of therapy
      were achieved. In women treated with intranasal salmon calcitonin, estradiol, FSH
      and LH levels were unchanged. Our results show that prolactin levels decrease
      significantly during the second year of the menopause. Neither combined
      estrogen/androgen, nor salmon calcitonin therapy had any effect on serum
      prolactin concentrations in postmenopausal women.

PMID- 9272426
TI  - Impact of combined hormone replacement therapy on serum lipid metabolism: new
      aspects.
AB  - The objective of this study was to evaluate the impact of combined estrogen
      progestogen therapy on low density lipoprotein (LDL) particle size (determined by
      the LDL cholesterol/apolipoprotein B ratio). The prospective study was carried
      out on 139 healthy Danish early postmenopausal women. The subjects were
      randomized to placebo or to 2 mg estradiol valerate equivalents, either
      sequentially combined with 75 micrograms levonorgestrel, 10 mg
      medroxyprogesterone acetate (MPA), or 150 micrograms desogestrel, or continuously
      combined with 1 mg cyproterone acetate. LDL particle size was calculated before
      treatment and at nine-well-defined times during the subsequent 84 days. LDL
      particle size was reduced by all four treatments. This change was statistically
      significant for estradiol valerate combined with levonorgestrel and MPA (6.2 +/-
      2.7% and 5.6 +/- 2.1% (mean +/- SEM), respectively; p < 0.05 for both, placebo
      corrected). Estradiol valerate combined with MPA induced cyclic (progestogen
      minus estrogen-related values) decreases (-6.3 +/- 2.6%; p < 0.05), and with
      levonorgestrel there were cyclic increases (5.1 +/- 2.7%; p = 0.067) in LDL
      particle size (placebo-corrected). In conclusion, combined estrogen-progestogen
      therapy causes a decrease in LDL particle size. A cyclic variation in LDL
      cholesterol/apolipoprotein B ratio was observed during sequential treatment.

PMID- 9272427
TI  - Bone density changes in postmenopausal women with the administration of
      ipriflavone alone or in association with low-dose ERT.
AB  - Ipriflavone is a synthetic flavonoid that has been shown to exert a direct
      inhibitory effect on osteoclastic activity and possibly stimulate the osteoblast
      activity in different experimental models. The aim of the present study was to
      evaluate the effects of either ipriflavone alone or ipriflavone plus low dose
      hormone replacement therapy (HRT) in the prevention of postmenopausal bone loss.
      Patients were randomly allocated to different treatment groups receiving calcium
      (500 mg/day, control group), continuous HRT (25 or 50 micrograms/day of
      transdermal 17 beta-estradiol) plus medrogestone 5 mg/day for 12 days/month,
      ipriflavone at the standard dose of 600 mg/day, or finally ipriflavone 600 mg/day
      plus 17 beta-estradiol 25 micrograms/day plus medrogestone 5 mg/day for 12
      days/month. No significant differences in basal levels of biochemical markers of
      bone turnover or in basal bone mineral density (BMD) values were evident in the
      different groups. In the control group after 12 months, spine BMD showed a
      significant (p < 0.05) 3.41% decrease. The pattern of BMD modification was
      significantly different from controls in the high dose HRT group (+1.84%), the
      ipriflavone group (+0.11%), and the combined ipriflavone/HRT group (-0.22%).
      Conversely, the BMD pattern in the low dose HRT group (-0.55%) was similar to
      that observed in controls. Thus, present results confirm that ipriflavone and 50
      micrograms/day of transdermal 17 beta-estradiol are effective measures in the
      prevention of postmenopausal osteopenia. A lower transdermal estrogen dose is
      unable to increase the antiresorptive effect of ipriflavone and did not exert any
      further action in the prevention of postmenopausal osteopenia.

PMID- 9272428
TI  - Developmental expression of a novel Kexin family protease, PACE4E, in the rat
      olfactory system.
AB  - PACE4 is a mammalian Kexin family protease that is involved in the maturation of
      precursor proteins. Four PACE4 isoforms have been identified. We identified a
      novel PACE4 isoform, PACE4E, from a human cerebellum cDNA library, which
      possesses a hydrophobic cluster in its C-terminus participating in membrane
      association. The size of PACE4E mRNA from adult rat brain was estimated by
      Northern blotting to be 4.4 kb. In situ hybridization histochemistry revealed
      that the highest level of PACE4E mRNA was expressed in the mitral cells of the
      adult rat olfactory bulb (OB). The OB is a unique sensory organ in that it has a
      lifelong regenerating capacity and it affects brain development. We further
      analyzed the expression of PACE4E mRNA in the developing olfactory system. On day
      13.5 of gestation, PACE4E mRNA was expressed at high levels in the
      neuroepithelium of the forebrain vesicle (FV), olfactory epithelium, and cells in
      the fiber bundles projecting to the FV. As development proceeded, PACE4E mRNA was
      expressed in developing mitral cells but decreased in the olfactory epithelium.
      In the newborn, its expression was confined to the mitral cells in both the main
      and accessory OB and in some periglomerular cells, as shown in adult rats. The
      spatio-temporal expression of PACE4E suggests that it plays a role in the
      establishment and maintenance of the olfactory receptor system.

PMID- 9272429
TI  - Immunoelectron microscopic study of the luminal release of serotonin from rat
      enterochromaffin cells induced by high intraluminal pressure.
AB  - Since definitive morphological studies showing the luminal release of serotonin
      have not been reported, we used a perfused system which allows physiological
      monitoring and biochemical as well as morphological evidence indicating release
      of serotonin from enterochromaffin cells. Isolated vascularly and luminally
      perfused rat duodenums exposed to 5-35 cmH2O of luminal pressure were measured
      for release of serotonin into the blood vessels and intestinal lumen. Immediately
      after raising the luminal pressure, the duodenum was fixed for immunoelectron
      microscopic localization of serotonin. Peristaltic contraction and serotonin
      content of the perfusates were continuously measured. The luminal release of
      serotonin increased with elevated intraluminal pressure, but the vascular release
      of serotonin was not altered. Tetrodotoxin had no effect on the pressure
      stimulated luminal serotonin release. Enterochromaffin cells in control animals
      without increased luminal pressure contained immunogold-labeled secretory
      granules in the apical and basal cytoplasm. After intraluminal pressure
      increased, many apical secretory granules were no longer dense and immunogold
      particles were localized over the cytoplasmic matrix and microvilli. These
      findings indicate that luminal serotonin release is increased after raising the
      intraluminal pressure and serotonin, normally stored in the secretory granules of
      enterochromaffin cells, appears to be released into the cytoplasmic matrix and
      then diffuses or is transported into the intestinal lumen.

PMID- 9272430
TI  - Comparison of the DNA content of megakaryocytes identified immunologically with
      that identified morphologically.
AB  - We devised a new microfluorometric method for determining the ploidy of
      megakaryocytes identified immunologically in bone marrow smears. The smears were
      immunostained by incubation with mouse monoclonal anti-glycoproteins (GP) IIb
      antibodies, followed by fluorescein isothiocyanate-conjugated goat antimouse IgG
      antibodies. They were then stained with 4',6-diamidino-2-phenylindole (DAPI).
      Megakaryocytes were identified by their GPIIb immunofluorescence using a
      microfluorometer and, after the filters were changed, their DNA content was
      assayed by measuring the intensity of DAPI fluorescence. This intensity was shown
      to be proportional to the DNA content when the aperture of the objective lens was
      reduced. We compared these results with those obtained when megakaryocytes were
      identified morphologically, using DAPI staining after Wright-Giemsa destaining.
      In all 12 normal controls, the ploidy peaks were shown to be 16N by both methods,
      and the mean ploidy detected by the immunological method was only reduced 0.961
      times relative to the estimate from the morphological method. In contrast, in
      eight myelodysplastic syndrome (MDS) patients, the ploidy peaks were either 8N or
      4N and the mean was reduced by 0.906 times (P = 0.018). Thus we could
      immunologically identify small megakaryocytes which we could not identify
      morphologically. Therefore, this method is useful for measuring megakaryocytic
      ploidy, especially in the pathological megakaryocytes of MDS patients.

PMID- 9272431
TI  - Immunocytochemical localization of thrombomodulin in the aqueous humor passage of
      the rat eye.
AB  - This report describes the distribution and localization of thrombomodulin (TM) in
      the rat eye by light and electron microscopic immunocytochemistry. In addition to
      the endothelium of the entire vasculature, TM was found on the non-vascular
      structures lining the cavities of the posterior and anterior chambers and the
      limbus. TM was localized on the basal, lateral, and apical plasma membranes of
      the inner and outer ciliary epithelium, and the posterior iris epithelium in
      which there was no polarized expression of TM. In the anterior chamber, TM was
      localized on the luminal surface of the corneal endothelium, but was negative on
      the anterior border layer of the iris, which is composed of a discontinuous layer
      of fibroblasts and collagen fibers. Thus, TM was present at sites of cell-to-cell
      contact. TM was also present on the endothelia of the trabecular meshwork and the
      Schlemm's canal in the limbus. TM was localized not only on the luminal plasma
      membrane, but also on the cytoplasmic giant vacuoles in the endothelial cells of
      the Schlemm's canal. These findings extend the importance of anticoagulant
      mechanisms to the systems of secretion, circulation, and drainage of the aqueous
      humor.

PMID- 9272432
TI  - Rodent pancreatic islet cells contain the calcium-binding proteins calcineurin
      and calretinin.
AB  - Calcium is known to be of critical importance for hormone secretion in the
      insulin-producing B-cells of the endocrine, pancreas. Calcium-mediated
      intracellular signal transduction and the regulation of the concentration of free
      calcium in B-cells probably involve calcium-binding proteins. In the present
      study, we have investigated the expression of the calcium/calmodulin-dependent
      phosphatase, calcineurin, and the EF-hand calcium-binding protein, calretinin, in
      pancreata of hamsters, gerbils, and rats by immunocytochemistry.
      Immunocytochemical investigations of serial semithin sections of plastic-embedded
      pancreata revealed that calcineurin and calretinin were constantly present in
      islet cells of all three species. In addition to B-cells, these proteins could
      also be detected in glucagon (A-), somatostatin (D-), and pancreatic polypeptide
      (PP-) cells. Non-B-cells, especially glucagon-producing A-cells, often exhibited
      a significantly higher degree of immunoreactivity for both calcium-binding
      proteins than B-cells. Thus, calcineurin and calretinin may play distinct roles
      in the regulation of calcium-dependent secretory activities of the different
      pancreatic endocrine cell types.

PMID- 9272433
TI  - Microphotometric determination of structure-bound oxidoreductase activities
      avoiding nothing-dehydrogenase artefacts: succinate dehydrogenase.
AB  - A tetrazolium-based microphotometric method has been devised for the
      determination of structure-bound dehydrogenase activities with correction for
      nothing-dehydrogenase artefacts. The method is based on the microphotometric
      recording of maximum reaction rates in a simple incubation chamber and consists
      of two successive measurements on the same section, the first in the absence and
      the second in the presence of the substrate. Following the first measurement, the
      substrate-free medium is quickly exchanged with the substrate-containing medium
      and a second measurement is taken. Subtraction of the first from the second
      reaction rate yields the enzyme activity corrected for nothing-dehydrogenase.
      Measurements of succinate dehydrogenase (SDH) in skeletal muscle fibres, liver,
      cardiac atrium and ventricle demonstrate the feasibility of the method.
      Measurements on the extensor digitorum longus muscle of rat reveal a range of up
      to fivefold differences in SDH activity within the fibre population of this
      muscle.

PMID- 9272434
TI  - Effects of cholinergic and alpha-adrenergic agonists on the monovalent ion
      content of rat submandibular gland acinar cells studied by X-ray microanalysis.
AB  - The effects of cholinergic and alpha-adrenergic stimulation (in vivo and in
      vitro) on the monovalent ion content of rat submandibular gland acinar cells were
      evaluated at the subcellular level by X-ray microanalysis. Fragments of glands or
      enzymatically dispersed acini were slam-frozen and cut into ultrathin
      cryosections. Spectra were collected from secretory granules, nucleus, the basal
      cytoplasm containing endoplasmic reticulum and the apical cytoplasm identified
      between secretory granules. No significant changes in Na and Cl content were
      observed after the isolation of acini, but the K concentration decreased compared
      with cells from in situ glands. The Cl and K content in all four compartments
      studied decreased significantly after cholinergic stimulation both in vivo and in
      vitro but in a more restricted fashion after alpha-adrenergic stimulation. Our
      findings indicate that: (1) the physiological mechanisms regulating the
      monovalent ion composition of submandibular cells are relatively well preserved
      in isolated acinar cells; (2) the results from in vivo experiments are in good
      agreement with those from in vitro experiments; and (3) the effects of
      cholinergic and alpha-adrenergic stimulation on the K+ and Cl- efflux at the
      subcellular level are similar but the response is generally less with alpha
      adrenergic stimulation.

PMID- 9272435
TI  - Neuroendocrine-specific protein (NSP)-reticulons as independent markers for non
      small cell lung cancer with neuroendocrine differentiation. An in vitro
      histochemical study.
AB  - Neuroendocrine-specific protein (NSP)-reticulons have recently been discovered
      and were shown to exhibit a restricted, neuroendocrine/neural-specific expression
      pattern. These protein aggregates are anchored to the membranes of the
      endoplasmic reticulum and occur in small cell lung cancer (SCLC), but not in
      typical non-SCLC. In the current study we have examined the occurrence of NSP
      reticulons in non-SCLC cell lines known to express neuroendocrine features (non
      SCLC-NE). NSP-reticulon expression was observed in all three non-SCLC-NE cell
      lines studied, albeit with variable intensity and in varying numbers of cells.
      Western blot analysis confirmed the presence of NSP-reticulon expression in these
      non-SCLC-NE cell lines, and showed that they were predominantly of the NSP-A
      type. When compared to conventional neuroendocrine markers, NSP-reticulons
      revealed a distinct staining profile, showing only partial overlap with the other
      markers. The non-SCLC-NE cell lines combined these neuroendocrine characteristics
      with some features of non-SCLC. We conclude that NSP-reticulon expression is
      restricted to lung carcinoma cells with a neuroendocrine phenotype and predict
      that these constituents may become clinically relevant markers for the detection
      of neuroendocrine differentiation in solid tumours.

PMID- 9272437
TI  - The multidrug-resistance P-glycoprotein (Pgp, MDR1) is an early marker of blood
      brain barrier development in the microvessels of the developing human brain.
AB  - The multidrug-resistance P-glycoprotein (Pgp) was initially identified as an
      energy-dependent proton pump, which transports a variety of non-related compounds
      out of chemotherapy-resistant cancer cells. Molecular biological investigations
      using knockout mice for the mouse homologue of the human Pgp showed that these
      mice partially lack a functioning blood-brain barrier, indicating that Pgp has an
      important role in the blood-brain barrier as its normal function. The presence of
      Pgp expression in formalin-fixed and wax-processed tissue sections can be
      assessed using the monoclonal antibody, JSB-1. Since no data on the developmental
      expression of Pgp are available, we stained a developmental series of human brain
      sections with JSB-1. Our results indicate that Pgp expression in endothelia of
      brain microvessels occurs regularly in embryos of about 30-mm crown-rump length
      (CRL). Strong reactivity is seen in blood vessels of fetuses from 123-mm CRL.
      There is also reactivity in pial blood vessels but not in choroid plexus blood
      vessels known to be without a blood-brain barrier. Pgp expression is therefore an
      early marker of the blood-brain barrier in the developing human brain.

PMID- 9272436
TI  - Use of low temperature and high K+ incubation media for in vitro tissue
      preparation for X-ray microanalysis.
AB  - Incubation of tissue slices in physiological buffers gives rise to significant
      changes in the intracellular ion concentrations, which may disturb subsequent X
      ray microanalysis. In the present study it was attempted to design incubation
      conditions that retain the in vivo conditions better. The following variables
      were investigated: (1) exchange of Na+ in the incubation medium for K+, and
      exchange of Cl- for the less permeable gluconate anion; (2) incubation at 4
      degrees C rather than at 37 degrees C; and (3) addition of dextran to the
      incubation medium. Brief exposure (a few seconds) of liver slices to a buffer
      causes changes in the intracellular Na, Cl and K concentrations, depending on the
      ionic composition of the buffer. Incubation in a normal physiological (high NaCl)
      buffer at 37 degrees C results in a further increase of Na and Cl and a further
      decrease in K in liver cells. The changes reach a maximum at 30 min and the
      concentrations then remain stable throughout a 2-h incubation. Incubation in
      sodium gluconate medium or addition of dextran to the physiological buffer
      somewhat reduces the changes in the intracellular ion composition (compared to
      the standard physiological incubation medium). Incubation in potassium gluconate
      medium results in a decrease in cellular Na and an increase in K. Quantitative
      morphological studies show that tissue oedema is observed to the same extent in
      hepatocytes incubated in sodium gluconate, potassium gluconate and physiological
      buffer containing 10% dextran. However, these buffers cause significantly less
      cell oedema than the physiological (high NaCl) buffer. Incubation of liver,
      cerebral cortex or submandibular gland slices in physiological (high NaCl)
      solutions at 4 degrees C for 4 h caused a more extensive increase in Na+ and
      decrease in K+ than incubation at 37 degrees C for 2 h. This suggests inhibition
      of the Na+, K(+)-ATPase under these conditions. As compared to incubation at 37
      degrees C for 2 h, tissues incubated in potassium gluconate buffer at 4 degrees C
      for 4 h have a cellular K concentration closer to the in situ value. Cholinergic
      stimulation of tissue slices from cerebral cortex and submandibular gland at room
      temperature for 1 min shows the best physiological response in tissue slices
      preincubated at 4 degrees for 4 h in high KCl, potassium gluconate and high NaCl,
      in this order. The response can, however, only be seen, when cholinergic
      stimulation is carried out in a standard physiological buffer with a high NaCl
      concentration. It is concluded that in vitro storage of tissue for X-ray
      microanalysis is best carried out at 4 degrees C in a solution with a high K+
      concentration.

PMID- 9272438
TI  - Generation of clonal diversity by sexual reproduction in the greenbug, Schizaphis
      graminum.
AB  - In the United States, the greenbug, Schizaphis graminum (Rondani), reproduces
      primarily by apomictic parthenogenesis. Although a periodic sexual cycle exists,
      the extent to which it occurs naturally and its influence on the genetic
      variability of greenbug populations is unclear. Length variation in the
      intergenic spacer (IGS) of the rRNA cistron in the greenbug indicates that
      populations are made up of many genetically distinct clones. Previous laboratory
      studies have shown the stability of the IGS within parthenogenetic clones. By
      inducing the sexual reproductive cycle of the greenbug, we conducted both Intra-
      and inter-clone matings and studied the inheritance of the IGS in the offspring.
      In both mating schemes, rearrangements in the IGS were apparent. IGS diversity
      found among the offspring could be attributed to unequal cross-over and probably
      other molecular drive events during meiosis. Periodic sexual reproduction is a
      primary mechanism for the generation and maintenance of genetic variability in
      greenbug populations, and explains the level of clonal diversity found in
      previous studies.

PMID- 9272439
TI  - Mitochondrial haplotypes and phylogeography of Phlebotomus vectors of Leishmania
      major.
AB  - Haplotypes of eight phlebotomine species were characterized by cycle sequencing a
      mitochondrial (mt) DNA fragment (cytochrome b to NADH1) amplified from single
      sandflies by PCR. Phlebotomus (Phlebotomus) papatasi displayed little variation
      throughout its large geographical range. We conclude that this vector of
      Leishmania major suffered a population bottleneck late in the Pleistocene and
      then radiated out from the eastern Mediterranean subregion. There was no support
      for a recent domestic lineage of P. papatasi. The mtDNA molecular clock in
      phlebotomines (subgenera Phlebotomus and Larroussius) was calibrated by reference
      to palaeogeographical events in Africa and the Mediterranean subregion. It fitted
      a pairwise nucleotide sequence divergence rate of 1.0-2.5% per million years. Co
      evolution of L. major, its Phlebotomus vectors and mammalian reservoirs is
      discussed.

PMID- 9272440
TI  - Reassessment of 79B actin gene expression in the abdomen of adult Drosophila
      melanogaster.
AB  - The expression pattern of the 79B actin gene in Drosophila melanogaster has been
      inferred previously by means of a reporter gene in which 79B actin promoter
      sequences drive the lacZ coding sequences. Although the 79B actin gene is
      expressed primarily in muscles of the thorax and first abdominal segment of the
      adults of both sexes, expression in the remaining abdominal segments appears
      limited to the male genital muscles and the male-specific Muscle of Lawrence
      (MOL). This reported abdominal expression pattern has been reassessed. By varying
      parameters of tissue preparation and lacZ reporter gene detection, expression of
      the 79B actin gene has been revealed in most dorsal abdominal longitudinal fibres
      and genital muscles of both females and males. These new results suggest that
      there are differences in the level of 79B actin gene expression among the various
      abdominal muscles of both sexes, and that abdominal expression is not limited
      primarily to male sex structures.

PMID- 9272441
TI  - The phylogenetic relationships of seven European Ips (Scolytidae, Ipinae)
      species.
AB  - In Central Europe seven lps species are characterized by differences in
      morphology, structure of galleries, host specificity and aggressiveness. These
      species were analysed by allozyme markers and by sequencing 567 bp of the
      mitochondrial cytochrome oxidase I gene, in order to define their phylogenetic
      relationships. Orthotomicus erosus and Tomicus minor were taken as outgroup
      species. The data revealed high inter-specific and low intra-specific sequence
      divergence. Plotting the observed sequence divergence caused by transversions
      (Tv) and transitions (Ts) and the level of saturation for Ts and Tv of each codon
      position showed that the third positions were highly saturated by multiple
      substitutions. Maximum parsimony analysis produced two groups: (1) I.
      typographus, I. cembrae, I. amitinus, I. duplicatus and I. acuminatus; (2) I.
      mannsfeldi, I. sexdentatus and the two outgroups. In all analyses the species of
      the first cluster were put together and I. typographus and I. cembrae, and I.
      mannsfeldi and O. erosus emerged as sister pairs. The data do not support a
      common ancestor for the seven European lps species. The eight-spined bark beetles
      (except I. mannsfeldi) and I. acuminatus formed a monophyletic group. The close
      relationship of I. mannsfeldi and O. erosus supports the latter belonging to the
      genus lps as proposed by Wood (1982) and Escherich (1923). However, more genetic
      markers and more species of the genera Orthotomicus and Pityokteines have to be
      analysed to resolve the phylogenetic positions of I. sexdentatus I. mannsfeldi
      within the tribe lpinl.

PMID- 9272442
TI  - Ccmar1, a full-length mariner element from the Mediterranean fruit fly, Ceratitis
      capitata.
AB  - Using a PCR primer specific to the ITR sequence of a deleted mariner element we
      amplified a fragment of approximately 1300 bp from the genome of Ceratitis
      capitata. Analysis of four clones showed that they differed by approximately 4.6%
      in nucleotide sequence and exhibited high homology to mariner elements of the
      mellifera subfamily. One clone in particular, Ccmar1.18, was found to possess an
      ORF of 338 amino acids together with many of the features typical of mariner
      elements. The consensus sequence, Ccmar1, derived from these clones is presented.
      Maximum parsimony phylogenetic analysis of the Ccmar1 element confirms its
      position at the periphery of the mariner mellifera subfamily. The Ccmar1 element
      is estimated to be present in about 500 copies in the genome. The evolutionary
      history of the element in relation to the colonization history of the medfly is
      discussed.

PMID- 9272443
TI  - Mitochondrial DNA sequence divergence in weevils of the Pissodes strobi species
      complex (Coleoptera:Curculionidae).
AB  - Mitochondrial DNA sequence divergence is unusually high between several species
      of the Pissodes strobi complex, in contrast to low allozyme and morphological
      divergences, and the ability to hybridize in the laboratory. We sequenced an 810
      bp segment in seven individuals, representing four species in the P. strobi
      complex and one outgroup species, P. affinis Randall. The 810 bp segment covered
      the 3' half of the cytochrome oxidase subunit I (COI) gene. We also sequenced one
      specimen of P. strobi (Peck) over a 2301 bp region of mtDNA, extending from the
      5' end of COI to the 3' end of COII. Uncorrected sequence divergences were below
      1.1% among three specimens of P. schwarzi Hopkins, and between P. terminalis
      Hopping and P. nemorensis Germar. All other interspecific combinations in the P.
      strobi complex showed divergences of 6.0-7.5%. The outgroup species, P. affinis,
      had an average divergence of 12.8% from members of the P. strobi group. As in
      most other insects, A + T content in Pissodes mtDNA was high;
      transition:transversion ratio was high among lineages exhibiting low divergences,
      but declined with increasing sequence divergence; and inferred amino acid
      sequence divergences were low. The degree of sequence divergence differs markedly
      across different functional regions of the COI gene. The high mtDNA divergences
      within the P. strobi complex calculated from direct sequencing support earlier
      reports based on restriction site surveys; however, cladograms based on mtDNA
      sequence differ from those based on earlier work.

PMID- 9272444
TI  - Cloning and sequence of a gene for the homologue of the stearoyl CoA desaturase
      from salivary glands of the tick Amblyomma americanum.
AB  - A 1488 base pair cDNA clone has been isolated from a cDNA library made from
      salivary glands from 3-day feeding adult female ticks. The sequence of this cDNA
      suggests it is the gene for the tick homologue of the stearoyl CoA desaturase.
      This gene is expressed in eggs and all feeding stages of the adult examined, but
      appears to be transcribed to an 8 kb mRNA as well as a 1.5 kb mRNA. Because ticks
      have the ability to synthesize monounsaturated fatty acids and demonstrate a
      large increase in salivary monounsaturated fatty acids during tick feeding, we
      hypothesize that stearoyl CoA desaturase may be a key enzyme in the morphogenesis
      of tick salivary glands during feeding.

PMID- 9272445
TI  - Phylogenetic relationships of the Alyslinae/Opiinae (Hymenoptera:Braconidae) and
      the utility of cytochrome b, 16S and 28S D2 rRNA.
AB  - Subfamily to generic level relationships among the Opiinae and Alysiinae
      (Hymenoptera: Braconidae) were investigated using DNA sequence data from c. 400
      bp fragments of the cytochrome b, 16S rRNA and 28S D2 rRNA genes. The best
      recovery of morphologically-defined groups was achieved by 28S D2, followed by
      16S with cytochrome b being very uninformative. We suggest ribosomal expansion
      regions may prove useful for this level of phylogenetic reconstruction. Combined
      analyses on all genes (using several alignment and phylogenetic methods) improved
      resolution but failed to resolve the proposed paraphyly of the Opiinae and
      Alysiini. Support was found for other relationships within the Opiinae and,
      contrary to a previous morphological study, there was strong evidence against the
      Gnamptodontinae being the sister group of the Opiinae/Alysiinae clade.

PMID- 9272446
TI  - Genetic differentiation between and within strains of the saw-toothed grain
      beetle, Oryzaephilus surinamensis (Coleoptera: Silvanidae) at RAPD loci.
AB  - Nine strains of Oryzaephilus surinamensis have been kept in laboratory culture
      for periods ranging from 5 to 30 years (30-180 generations). Two RAPD primers
      provided sufficient information to separate the strains reliably and
      unambiguously. The strains are maintained at a population size of 200 breeding
      adults. The marked divergence between strains is consistent with the small
      population size, which for the older strains, according to population genetics
      theory, implies that roughly half the original genetic variation should now be
      lost from within strains. However, there is no indication that the older strains
      have less inter-strain variation. The results demonstrate RAPD loci can reliably
      detect population subdivision, which in field populations of pest species is of
      fundamental importance in understanding the population genetics of insecticide
      resistance.

PMID- 9272447
TI  - The white gene from the yellow fever mosquito, Aedes aegypti.
AB  - We report the cloning and primary characterization of both cDNA and genomic
      fragments from the white gene of the yellow fever mosquito, Aedes aegypti.
      Comparisons of the conceptual translation product with white genes from four
      other species within the order Diptera show that the Ae. aegypti gene is most
      similar to the white gene of the mosquito vector of human malaria, Anopheles
      gambiae (86% identity and 92% similarity). The analysis of the primary sequence
      of genomic DNA at the 5'-end of the coding region revealed the presence of an
      intron that is also present in An. gambiae, but not in the vinegar fly,
      Drosophila melanogaster. The isolated clones of the Ae. aegypti white gene will
      enable the construction of a marker gene for use in the development of a germline
      transformation system for this species.

PMID- 9272448
TI  - Phylogenetic characterization of two transovarially transmitted endosymbionts of
      the bedbug Cimex lectularius (Heteroptera:Cimicidae).
AB  - Two different inherited bacterial symbionts from ovary tissue of the bedbug Cimex
      lectularius were characterized by gene amplification and sequencing analysis of
      their 16S rDNA gene. The first bacterium belongs to the Wolbachia subgroup of the
      alpha-Proteobacteria, the second is a member of the gamma-subdivision, and is
      closely related to the bacterial parasite of the leafhopper Euscelidius
      variegatus (BEV) which was shown to be capable of transovarial transmission. The
      high similarity (> 97%) between the C. lectularius symbiont and BEV indicates
      that these two microorganisms belong to the same lineage and share the ability to
      invade distant insect hosts to fulfill their symbiotic functions and to establish
      transovarial transmission to future generations.

PMID- 9272449
TI  - Post-operative faecal continence in patients with ulcerative colitis after ileo
      anal anastomosis with preservation of the transitional zone: a report from a low
      incidence region.
AB  - The aim of this prospective study was to analyse post-operative faecal continence
      by carrying out a manometric and clinical follow-up on ten patients previously
      suffering from ulcerative colitis, who underwent total proctocolectomy and double
      stapled ileo-anal anastomosis with preservation of the transitional zone. An
      annual histological analysis of the transitional zone was performed post
      operatively. A 13% reduction in the length of the high-pressure zone of the anal
      canal (P = 0.04) was observed without any significant change in the resting anal
      pressure or the maximal squeeze pressures. Fifty percent of the patients showed
      histological signs of inflammation, without any clinical manifestations. The
      median number of bowel movements was 4 per day and 1 per night, and only 1
      patient had occasional nocturnal soiling (less than once a week). On being
      questioned, 9 patients replied that they rated their continence as good or very
      good and 1 patient, as reasonable. These findings show that ileo-anal
      anastomosis, without mucosal resection preserves the normal resting anal pressure
      and anal function despite the reduction in the length of the high pressure zone
      it involves.

PMID- 9272450
TI  - The value of endorectal ultrasound in the assessment of adenomas, T1- and T2
      carcinomas.
AB  - In a prospective study we examined the value of endorectal ultrasound (ERUS) in
      the preoperative staging of potentially locally excisable tumours. During the
      study period from 1.1.1991 to 1.3.1996 a total of 160 rectal tumours in 152
      patients were staged endosonographically (uT/uN) and compared postoperatively
      with the histologic result (pT/pN) at the University Hospital of Wurzburg. Thirty
      eight (24%) patients had an adenoma and 15 (9%) a T1-carcinoma. In 29 (18%) cases
      a T2-cancer was diagnosed, further 67 (42%) and 11 (7%) patients presented with a
      T3 and T4 tumour, respectively. The sensitivity for adenomas and T1-Ca (uT0/1)
      was 81%, the specificity 98%. For T2 tumours, the sensitivity was only 41% and
      the specificity 92% as the majority (17 of 29) of pT2 neoplasias were overstaged
      (uT3). The overall staging accuracy (T1-4) was 77.5%. Two patients with a pT1-Ca
      and seven with a pT2-Ca had lymph node metastases which were detected
      preoperatively in five. The accuracy for lymph node staging was 83%. We conclude
      that adenomas and T1 tumours can be assessed with a high grade of accuracy using
      ERUS. In these tumours ERUS can be used to assist clinical decision-making
      (transanal vs. abdominal operation). Owing to the lack of sensitivity ERUS is of
      no help in the assessment of T2 carcinomas.

PMID- 9272451
TI  - The effects of chronic ill health and treatment with sulphasalazine on fertility
      amongst men and women with inflammatory bowel disease in Leicestershire.
AB  - The aims of the study were to ascertain whether patients have similar a fertility
      rate to the background population in Leicestershire and whether they have a
      similar rate of congenital malformations compared to the background population in
      Leicestershire. Over 1400 patients were invided to participate with an overall
      response rate of 81% after three successive mailings. The response rate was
      similar for both sexes and between the disease groups. The crude infertility rate
      for the group was 21%. The mean number of children for the whole group was 1.7 +/
      1.3 but both men and women with Crohn's disease had significantly less children
      than would be expected, (men with Crohn's disease 1.5, women with Crohn's disease
      1.2). There were 39 children (2% of overall births) with congenital abnormalities
      reported by patients with inflammatory bowel disease and in 29 cases the parents
      reported taking sulphasalazine (Table 3). Although this figure compares well with
      the 1.8% reported congenital abnormality rate for Leicestershire within the
      patient group in this study congenital malformations were significantly related
      to sulphasalazine use, z = 4.3, P < 0.0001. In conclusion sulphasalazine not only
      as causes morphological abnormalities in spermatozoa but may increase the chances
      of having congenitally abnormal offspring amongst men with IBD. The effects of
      other 5-aminosalacylic acids have yet to be studied in detail.

PMID- 9272452
TI  - Effects of age on anal function in normal women.
AB  - PURPOSE: To study effects of age on anal function in healthy women. METHODS: A
      study of 75 women with no known anorectal disease, aged 20 to 83 (mean 50) years,
      mean parity 2 (range 0-4). Perineal position at rest (PR), descent during
      straining (PS), maximum resting pressure (MRP) maximum squeeze pressure (MSP) of
      the anal sphincters, and pudendal nerve terminal motor latency (PNTML) were
      measured. Data were analysed using the multiple regression technique including
      age and parity in the model. RESULTS: Increasing age was significantly associated
      with a weakening of anal function. PR and PS were both lowered (P < 0.0001 and P
      = 0.0001). Anal sphincter pressures were reduced (MRP: P = 0.004, MSP: P =
      0.015), and age was associated with an increased mean PNTML (P < 0.0001). All
      associations seemed to be linear. Parity was associated with a lowering of both
      PR and PS but not with the other parameters. Age accounted for 13-44% of the
      total variability seen in the tests of pelvic floor function. CONCLUSION: Age
      leads to a consistent reduction in anal function and this is likely to increase
      the risk of faecal incontinence in old age. From the current data we suggest that
      in normal women with an uncomplicated obstetric history increasing age is
      associated with significant changes in anal function whereas long-term effects of
      vaginal deliveries play a minor role. Moreover our results suggest gradual
      changes throughout adult life, rather than large changes occurring after
      menopause.

PMID- 9272453
TI  - Small bowel length in inflammatory bowel disease.
AB  - Small intestinal length has a particular significance in patients with
      inflammatory bowel disease (IBD). A determination of intestinal length by a
      standardised and simple technique is of interest for surgical decision making in
      primary and recurrent disease and in the evaluation and management of
      postoperative malabsorption. The aim of the present investigation was to analyse
      intestinal length in patients with IBD and define a standard method for this
      measurement. MATERIAL AND METHODS: Two consecutive series of patients. Crohn's
      disease (n = 279) and ulcerative colitis (n = 315) and a control group (n = 77)
      underwent standardised intra-operative small intestinal length measurement.
      RESULTS: Small intestinal length correlated to weight and height and was less in
      women than in men (P < 0.001) in both IBD groups and the controls. The small
      bowel in patients with Crohn's disease was significantly shorter than in patients
      with ulcerative colitis and in controls, P < 0.001. Also in Ulcerative Colitis
      small bowel length was significantly less than in controls, P < 0.001. In CD
      patients there was no difference in bowel length with regards to the anatomical
      extent of the disease. Original small bowel-length in patients with CD and one or
      two bowel resections (n = 67) was not different from that in patients with three
      or more resections (n = 88). CONCLUSION: Small bowel length correlated to weight,
      height and sex. Patients with CD had a significantly shorter small intestine at
      first laparotomy, compared with U.C. patients and controls. In CD-patients there
      was no difference between the anatomical subgroups.

PMID- 9272454
TI  - Association between age and local recurrence of rectal cancer: results from a
      retrospective study of 902 patients.
AB  - Due to the ageing of the general population, there has been a relative increase
      of elderly patients with rectal cancer. The relation between age and the risk of
      local recurrence after apparently curative surgery for cancer of rectum and
      rectosigmoid was studied in a retrospective study of 902 patients, diagnosed from
      1984 through 1991 in the southwestern part of the Netherlands. Three age-groups
      were defined: 15-64 (n = 328), 65-74 (n = 327) and 75 and over (n = 247). After
      exclusion of postoperative deaths and controlling for unrelated causes of death,
      5-year survival rates were similar in the three age-groups (70%, 71% and 75%,
      respectively). Local recurrence rates, however, decreased with age from 23% to
      18% and 14%, respectively. In multivariate analysis, the hazard ratios were 1,
      0.84 and 0.66, respectively. These results suggest that local recurrence occurs
      less frequently in the elderly, which needs confirmation from prospective studies
      and warrants consideration in decisions about the use of adjuvant treatment.

PMID- 9272455
TI  - Is screening for thyroid carcinoma indicated in familial adenomatous polyposis?
      The Leeds Castle Polyposis Group.
AB  - Forty-five polyposis patients with thyroid carcinoma constituted 1.2% of the
      patients in the Leeds Castle Polyposis Group database. The patients were
      diagnosed during 1959-1995; 44 were females at a median age of 25 years (range 10
      40) and 37 (82%) had papillary carcinoma. At the end of 1995 only one patient
      (9%) had died from thyroid carcinoma, and the ten-year cumulative survival was
      84% (95% confidence limits 72-97). Due to the low incidence of thyroid carcinoma
      in FAP and the good prognosis we do not recommend a regular thyroid screening in
      polyposis, as this is unlikely to result in a reduction of the mortality, but
      will only aggravate existing cancrophobia in these strained patients.

PMID- 9272456
TI  - Internal anal sphincter repair.
AB  - The results of repair to the internal and sphincter alone has been evaluated in
      five patients with persistent anal incontinence following surgery which affected
      the internal anal sphincter. All had passive incontinence for solid or liquid
      stool. Symptoms, anorectal manometry, and anal endosonography were evaluated
      before and after surgery. After surgery three patients felt improved but had
      still persistent symptoms, and no patients achieved full continence. Three
      patients showed an increased maximal and resting pressure, but only one of them
      was within the normal range. Post operatively, all the anal ultrasound scans
      showed a persistent internal sphincter defect, and two showed an unsuspected
      external anal sphincter defect. Although some patients felt symptomatically
      improved, the overall clinical, manometric and radiological findings after
      internal and sphincter repair were disappointing.

PMID- 9272457
TI  - Dynamic imaging of the normal pelvic floor.
AB  - PURPOSE: To provide quantitative data by a modern cross-sectional imaging
      technique (CT) for defining normal physiological values of pelvic floor
      structures. PATIENTS AND METHODS: Twenty seven subjects, 7 males, 20 females,
      aged 20-75 yrs (mean 46.3 +/- 5 yrs) without pelvic floor or defection
      dysfunction underwent Direct Coronal (DC) CT scanning of the pelvis with the
      patient seated instead of lying. Scans obtained at rest and on straining were
      compared by bony landmarks. Three anatomical compartments, i.e. anterior, middle
      and posterior, were identified by two planes drawn tangential to the ischial
      foramina and the ischial tuberosities, respectively. Measurements of (1) Levator
      ani muscle length (mm); (2) Levator-anal angle (degrees); (3) Rectal floor-to
      ischial line distance (mm) and (4) Supra/Infralevator spaces (square cm) were
      independently performed twice by two radiologists. The statistical analysis
      included calculation of intra and interobserver agreement (correlation
      coefficient). The differences between the means of the resting and straining
      values from each compartment (Student's t test) and the correlation between
      parameters (Pearson's coefficient) to evaluate whether resting values allowed a
      prediction of those on straining were determined. RESULTS: DC scans of diagnostic
      quality were obtained in all but two patients (92.5%). Both intra- and
      interobserver agreement indices were always greater than 80% (except for a 0.63
      value by one observer obtained in the infralevator space from the anterior
      compartment at rest). A significant difference between the resting and straining
      values of all parameters was noted in the three compartments. At rest the levator
      ani muscle length was significantly shorter and the supralevator space smaller in
      the posterior compartment (48.3 +/- 7.9 mm vs 48.8 +/- 7 mm vs 42.6 +/- 9.4 mm, P
      < 0.05 and 70.6 +/- cm2 vs 66.9 +/- 11.5 cm2 vs 27.2 +/- 4.8 cm2, P < 0.01
      anterior, middle and posterior respectively). On straining, these two parameters
      increased by +42% and +17.8%, respectively, in the same compartment, while the
      most pronounced variation of the infralevator space occurred in the middle
      compartment (-51.1%). The increase in the supralevator space correlated with a
      decrease in the rectal floor-to-ischial line distance and widening of the levator
      anal angle (r = -0.64, P < 0.01 and 0.48, P < 0.05, respectively). A close
      correlation between resting and straining values was observed in all parameters,
      especially in the supralevator space in the three compartments (r = 0.82, 0.93
      and 0.88, P < 0.01). CONCLUSIONS: Direct Coronal CT scanning showed that on
      straining the posterior component of the levator ani muscle, i.e. the coccygeus
      muscle, undergoes "physiological overstretching" and the supralevator space acts
      as a "compliant cavity", whose behaviour can be predicted at rest.

PMID- 9272458
TI  - Cancer in the anal canal (transitional zone) after restorative proctocolectomy
      with stapled ileal pouch-anal anastomosis.
AB  - The first case of an adenocarcinoma developing in the retained anal canal mucosa
      (transitional zone) after restorative proctocolectomy with a stapled ileal pouch
      anal anastomosis is presented. The cancer was detected during routine follow-up
      16 months after pouch formation for long standing ulcerative colitis, complicated
      by a cancer in the upper rectum. The patient was treated with an abdominoperineal
      excision of the ileal pouch and anus.

PMID- 9272459
TI  - Congenital caecal cystic duplication presenting with caecal volvulus in an
      elderly woman.
AB  - Congenital caecal cystic duplication of the gastrointestinal tract usually
      present during infancy or young childhood. We have identified a patient who
      presented at 91 years of life with a caecal volvulus caused by a large
      communicating caecal cystic duplication. Review of the literature shows that
      caecal cystic duplications become symptomatic early when they cause
      complications, but until this report, volvulus was not a recognised presentation
      of caecal cystic duplication.

PMID- 9272460
TI  - Effect of L-arginine on reactivity of hamster cheek pouch arterioles during
      diabetes mellitus.
AB  - The goal of this study was to determine whether exogenous application of L
      arginine could restore impaired agonist-induced increases in arteriolar diameter
      during diabetes mellitus. We used intravital microscopy to examine reactivity of
      cheek pouch arterioles (50 microns in diameter) in nondiabetic and diabetic (2
      weeks after injection of streptozotocin) hamsters in response to histamine and
      substance P. In nondiabetic hamsters histamine (1.0 and 5.0 microM) dilated cheek
      pouch arterioles by 15 +/- 1 and 22 +/- 1%, respectively, and substance P (50 and
      100 nM) dilated arterioles by 14 +/- 3 and 21 +/- 4%, respectively. In addition,
      dilatation of arterioles in response to histamine and substance P in nondiabetic
      hamsters was abolished by application of an enzymatic inhibitor of nitric oxide
      synthase (L-NMMA). In contrast, histamine- and substance P-induced increases in
      arteriolar diameter were markedly reduced in diabetic hamsters. Histamine (1.0
      and 5.0 microM) dilated arterioles by only 5 +/- 1 and 4 +/- 2%, respectively,
      and substance P (50 and 100 nM) dilated arterioles by only 6 +/- 2 and 5 +/- 3%,
      respectively (p < 0.05 vs. nondiabetic hamsters). Nitroglycerin produced similar
      vasodilatation in nondiabetic and diabetic hamsters. Next, we examined whether
      exogenous application of L-arginine (100 microM) could restore impaired histamine
      and substance P-induced increases in arteriolar diameter in diabetic hamsters.
      We found that L-arginine did not restore altered nitric oxide synthase-dependent
      vasodilatation in diabetic hamsters. These findings suggest that short-term
      diabetes mellitus alters agonist-induced increases in arteriolar diameter. In
      addition, the mechanism of altered arteriolar reactivity during diabetes mellitus
      does not appear to be related to an impaired availability of L-arginine.

PMID- 9272461
TI  - The effects of two levels of vasomotor tone at physiologic suffusate PO2 on
      acetylcholine- and sodium nitroprusside-induced relaxation of cremaster third
      order arterioles in 5-hour ischemia-reperfusion control rats.
AB  - Intravital microscopy was used for 1 h in the cremaster skeletal muscles of
      normotensive 4- to 5-week-old rats. The total duration for experimentation was 5
      h in order to mimic the controls used previously for a 4-hour ischemia and 1-hour
      reperfusion model which was equilibrated with room air. Responsiveness of third
      order (3A) arterioles with resting vasomotor tone (VT) was assessed to topically
      applied 10(-2) to 10(-6) M acetylcholine (ACh) or sodium nitroprusside (NP) using
      a suffusate PO2 of 25-30 mm Hg. ACh (10(-4) M) or NP (10(-6) M) were retested at
      this Po2 in 3A arterioles with norepinephrine (NE) (10(-6) M)-enhanced VT.
      Results were compared against those using room air to increase VT. No dose
      response relationships were demonstrated for ACh or NP in resting conditions.
      Moreover, our current and former responses were maximal and of a lesser magnitude
      than those reported by others using room air. All doses except 10(-4) or 10(-6) M
      ACh, or 10(-6) M NP, also severely depressed systemic arterial blood pressure.
      Enhancement of VT by 29% resulted in a 3-fold greater dilation to 10(-4) M ACh or
      10(-6) M NP. The relative increase in volumetric blood flow (Q) to ACh or NP was
      5.3-5.7 times greater than with resting VT. However, there were no differences in
      the absolute maximal values attained for internal diameter (D) or Q between
      drugs. The times to peak response and recovery were accelerated for Q but not D
      in NE-preconstricted arterioles, and the relative increases in D were less than
      reported by others after equilibration with room air. At both levels of tone,
      topical administration of NE at the end of each experiment caused similar
      decreases in D and Q, while mean centerline cellular velocity, wall shear rate
      (WSR), and VT were found to increase. These results suggested that the relative
      increases in D and Q were due to NE-induced decreases in absolute predrug
      baselines, while both the depressed VT and peak responses in D were caused by a
      fall in vasoreactivity. Po2 did not appear to be a factor attenuating endothelium
      dependent responses, since ACh was equipotent to NP in resting or NE
      preconstricted arterioles at physiological suffusate Po2 or in cremaster flaps
      equilibrated with room air. Therefore, either NE at physiological suffusate Po2
      or room air appears acceptable for elevating initial VT/WSR when examining the
      endothelium-dependent and endothelium-independent mechanisms regulating
      physiological (dilator) tone and perfusion in 3A arterioles.

PMID- 9272462
TI  - Evaluation of the number of laser-Doppler measurements in assessing regional
      diaphragmatic microcirculation.
AB  - As regional diaphragmatic microvascular blood flow varies widely, the aim in this
      study was to estimate the number of repeated measurements, obtained by Laser
      Doppler flowmetry (LDF), required to achieve a standard level of precision. In 40
      urethane-anesthetized Sprague-Dawley rats, computer-aided LDF scanning coupled
      with a microscope generated diaphragmatic blood flow (Qdi) ranging between 94 and
      944 mV with the frequency histogram displaying non-Gaussian distributions. A
      sampling technique was used to assess the number of measuring sites required for
      valid estimates of the regional diaphragmatic microvascular flow. From a total of
      1,000 Qdi values, random samples of sizes between 5 and 100 were repeatedly drawn
      to estimate the variability of median flow. Our data shows that the 95th
      percentile decreased gradually, from a +30% error at n = 5 down to +20% at n = 15
      20, remained between +20 and +15% up to n = 35, and reached +10% at n = 50.
      Moreover, by expressing the precision level of measurements as the length of a
      95% confidence interval (beta), a linear relationship between beta values
      obtained either by the sampling method or repeated measures analysis of variance
      can be shown (r = 0.902, p < 0.001); beta values by either method were within +/
      20% error of the mean values at sample sizes above n = 15. It is therefore
      recommended that for microscope-guided LDF scanning in the assessment of the
      distribution of diaphragmatic microvascular blood flow, at least 15 repeated
      measurements should be done to reach an acceptable standard level of precision.
      However, facing with clinical situations where 'blind' LDF scanning inevitably
      includes measurements over large vessels, the minimal sample sizes required to
      represent tissue perfusion demand further exploration.

PMID- 9272463
TI  - Laser Doppler perfusion imaging of synovial tissues using red and near infra-red
      lasers.
AB  - A new laser Doppler perfusion imaging (LDI) system was evaluated by comparing it
      with the well-established radiolabelled microsphere technique for measuring blood
      flow in the rabbit knee joint capsule. In this study two laser sources (635 and
      835 nm) were compared at three scan speeds (50, 10 and 4 ms/pixel). With blood
      flow to the rabbit hindlimb controlled via a peristaltic pump, the comparison of
      LDI and microsphere measurement techniques yielded highly significant
      correlations for both laser sources (r = 0.9; p = 0.0001; 14 measurements in 7
      animals). Comparison of the three scan speeds demonstrated acceptable agreement
      without significant bias between measurements, suggesting that the inevitable
      narrowing of the bandwidth at the fastest scan speed does not cause significant
      deterioration of the signal. The flux values obtained with 635 and 835 nm laser
      sources were linearly related (r = 0.93, p = 0.0001; 66 measurements in 12
      animals), although there was a small but significant bias for higher values with
      the 635-nm laser (mean ratio of flux values 1.06, 95% confidence interval 1.01
      1.12). These results validate the use of LDI with either wavelength laser for the
      assessment of joint capsule perfusion.

PMID- 9272464
TI  - Microvascular endothelium of human tumor xenografts expresses mouse (= host)
      CD31.
AB  - BACKGROUND: Human malignant tumors grown as xenografts in immunocompromised
      animals have been used extensively to study tumor growth and tumor response to
      therapy. The endothelium functions as an effective barrier between the
      intravascular space and the tumor cells. In a previous study we used species
      specific monoclonal antibodies against endothelial cell adhesion molecules to
      demonstrate the host origin of the endothelium in xenotransplanted pancreatic
      islet grafts [Am J Pathol 1995;146:1397-1405]. We now investigated in this study
      whether the vascular endothelium of different xenografted human malignant tumors
      expresses mouse (= host)- or human (= graft)-specific CD31 (platelet endothelial
      cell adhesion molecule, PECAM-1) adhesion molecules. METHODS AND RESULTS:
      Cultured human prostate, kidney, and colon cancer cells (passages 15-17) were
      transplanted subcutaneously into 8-week-old athymic nude mice and removed after
      another 8 weeks. The avidin biotin peroxidase method was utilized on frozen
      sections to demonstrate that the endothelium of the vasculature of all three
      human xenografts expressed mouse (= host)-specific CD31, but not human (= graft)
      specific CD31. CONCLUSION: The presence between the intravascular space and the
      human tumor cells of a mouse-derived endothelium, expressing mouse-specific
      antigens, needs to be taken into careful consideration when evaluating results of
      antitumor therapies in these animal models. This caveat pertains particularly to
      the study of novel cell- or tissue-specific treatment modalities, such as
      antibody-targeted drugs, toxins or radionuclides, 'immuno'-liposomes, or tumor
      vaccines.

PMID- 9272465
TI  - Flow velocity of cutaneous lymphatic capillaries in patients with primary
      lymphedema.
AB  - For the first time measurements of lymph flow velocities in cutaneous
      microlymphatics of patients with lymphedema were performed and compared with
      healthy subjects. Flow velocity in single lymphatic skin capillaries was measured
      using fluorescence video microscopy after subepidermal microinjection of FITC
      dextran 150,000 in 15 healthy volunteers and 16 patients with primary lymphedema.
      Initial filling of the lymphatic capillary network was fast with significantly
      higher mean velocities in patients with primary lymphedema than in healthy
      controls (890 +/- 43 vs. 550 +/- 390 microns/s, p < 0.05). The resting velocities
      were not significantly different between controls and patients (10.3 +/- 4.1 vs.
      16.6 +/- 13.9 microns). In 12 out of the 16 lymphedema patients cutaneous
      backflow of the fluorescent contrast medium from deeper invisible lymphatics was
      observed. In 4 of these patients rhythmic reflux with a mean frequency of 1.4 +/-
      0.5 cycles/min was measured by video densitometry in microlymphatics with a
      significantly (p < 0.01) enhanced diameter. Mean flow velocity (Vp) in these
      precollectors was significantly increased compared to the resting velocities (p <
      0.01). On the basis of these results the hypothesis is advanced that rhythmic
      cutaneous backflow originates from intrinsic contractions of deeper lymph
      collector segments and is transmitted to the superficial microlymphatics through
      incompetent connecting channels. This newly recognized mechanism appears to be an
      important factor for the pathophysiology of lymphedema.

PMID- 9272466
TI  - Improved reproducibility of the 'large-window' method of assessing transcapillary
      and interstitial fluorescein diffusion in the skin in healthy subjects and in
      subjects with insulin-dependent diabetes mellitus.
AB  - The transcapillary and interstitial diffusion of intravenously administered
      sodium fluorescein is used as a marker for capillary permeability. Fluorescein
      diffusion has been expressed by different parameters with reported coefficients
      of variation of 14-20%. Aim of the present study is to select a parameter which
      combines excellent reproducibility with the potential for discriminating insulin
      dependent diabetic patients from healthy subjects. We performed three experiments
      to assess day-to-day reproducibility: 5 healthy subjects were measured twice, 1
      healthy subject was measured 6 times and 1 subject with insulin-dependent
      diabetes mellitus was measured 5 times. We averaged the relative fluorescence
      light intensity (IREL(t)] from dye arrival until a certain time point [IAV(t)],
      instead of using the relative intensity at one time point. IAV (7 min) showed
      markedly improved reproducibility, expressed as geometric mean of the
      coefficients of variation of the three separate experiments: 10%. In addition, a
      group of 12 insulin-dependent diabetic subjects was compared with 12 healthy
      control subjects. Median IAV (7 min) was 69.5% (95% CI: 65.3-78.1%) in the
      diabetic subjects and 54.9% (95% CI: 52.1-60.0%) in the control subjects (p <
      0.001). Since IAV (7 min) combines excellent reproducibility with a good
      discriminating power, we advise its use in further studies.

PMID- 9272467
TI  - Innervation of posterior structures in the lumbar spine of the rat.
AB  - OBJECTIVE: To determine the nature and distribution of afferent fibers to the
      interspinous tissues and facet joints of the lumbar spine in the rat. DESIGN:
      Dissection and photography of medial branch of the primary dorsal ramus;
      histological and electron microscopic examination of the medial branch;
      measurement of conduction velocities of fibers within the medial branch;
      recording of compound nerve activity in medial branch in response to mechanical
      and chemical stimulation of interspinous tissues and facet joints. RESULTS: In
      the rat, the medial branch of the primary dorsal ramus of lumbar spinal nerves is
      normally distributed to the facet joints and interspinous tissues one and two
      segmental levels caudad to its origin. This nerve contains unmyelinated and
      myelinated afferents with conduction velocities within the ranges of C fibers,
      and A-delta and A-beta fibers. The tissues served by this nerve are sensitive to
      mechanical and noxious chemical stimulation. CONCLUSIONS: There are many
      structural and functional similarities in the innervation of the lumbar spine in
      rats and humans. However, there are anatomical variants and, in rats, the medial
      branch of the primary dorsal ramus, which serves the interspinous tissues and
      facet joints, is distributed more caudally than in humans. This information
      should be taken into account in extrapolating experimental results from rats to
      the human situation.

PMID- 9272468
TI  - Normal response to large posteroanterior lumbar loads--a case study approach.
AB  - OBJECTIVE: Characterization of the responses to spinal posteroanterior loading
      has involved measuring the gradient of the linear region of the force
      displacement relationship between 30 N and 100 N of applied force. However,
      forces applied during manual assessment of stiffness may reach 300 N. This study
      investigated whether the force-displacement relation remains linear above 100 N.
      DESIGN: A single-case-study design with replication was used. SUBJECTS: Two male
      subjects, with no history of low back pain requiring treatment over the preceding
      twelve months, participated in this study. METHODS: Posteroanterior loads of 275
      N were applied to the 1.3 vertebra of both subjects using a mechanical device.
      The force-displacement responses in these subjects were measured and analyzed to
      examine the linearity of the data. RESULTS: The responses from the two subjects
      were similar. In both cases, the responses were approximately linear at all
      levels of load up to 275 N. Because of the small degree of nonlinearity, there
      was a tendency for the stiffness to show moderate increases as the load
      increased. Stiffness was approximately 25% greater when calculated between 30 N
      and 275 N than when calculated between 30 N and 100 N. CONCLUSION: In these two
      subjects, the force-displacement relation was approximately linear for all three
      force intervals considered, although there was some increasing stiffness with
      increasing force.

PMID- 9272469
TI  - Managed care preapproval and its effect on the cost of Utah worker compensation
      claims.
AB  - OBJECTIVE: To determine the effect of preauthorization of chiropractic services
      costs in non-surgical back injury cases in a managed care environment. The
      program was implemented in the chiropractic provider group by the Worker
      Compensation Fund of Utah. The results were compared with those of similar injury
      claims in a separate provider group in which there was no preauthorization
      program. DESIGN: The study was a retrospective review of approximately 5000
      claims from 1986 and 5000 claims from 1989 of injured workers in the Utah Worker
      Compensation Fund. We extracted approximately 1000 nonsurgical back-related
      injury claims from each year. MAIN OUTCOME MEASURE: Cost comparisons between
      medical and chiropractic provider groups in the management of nonsurgical
      compensable back pain in both 1986 and 1989. RESULTS: Treatment costs in cases
      managed by chiropractic physicians increased 12% between 1986 and 1989. Treatment
      cost in cases managed by medical physicians increased 71% in the same time
      period. Compensation (wage replacement) costs increased 21% for the chiropractic
      group and 114% for the medical group. CONCLUSION: Retrospective analysis of
      worker compensation databases continue to struggle with issues related to
      measurement of severity, appropriate condition identification, adequate inclusion
      of all related costs and unbiased case selection. Treatment costs appeared to be
      controlled under the auspices of a preapproval program required of the
      chiropractic physician whereas medical costs escalated in the absence of price
      controls.

PMID- 9272470
TI  - The chiropractic consultation: a stressful experience?
AB  - INTRODUCTION: Psychosocial stress has been linked to compromised health status.
      Prolonged exposure to minor problems has been found to have an equal or greater
      impact on health status than exposure to isolated major events. Stress is,
      however, determined by the reaction of the individual to a stimulus; stress
      responses can be managed, and ill health outcomes can be minimized. This paper
      explores the stress level associated with the chiropractic consultation. METHOD:
      A case study using closed questions. Purposive sampling of chiropractors by the
      researcher and convenience sampling of patients by participating chiropractors
      was undertaken. Chiropractors and patients completed closed questions on the
      level of stress they believed patients associated with the chiropractic
      consultation. RESULTS: A case study of 25 chiropractors and 137 patients found
      that although the chiropractic consultation was not regarded as stressful by most
      patients, some patients found adjustment stressful. Chiropractors assessment of
      perceived stress varied according to the patient. The trend was for practitioners
      to overestimate the stress felt by the patient. CONCLUSION: Chiropractors
      demonstrated the personalized nature of their care by the specificity of their
      responses to each patient. The importance of explaining the adjustment and the
      sensations that patients are likely to experience, particularly in new patients,
      is confirmed. The desirability of scrutinizing the patient for evidence of stress
      and of using diverse strategies for minimizing the stress response are discussed.
      Although the chiropractic consultation is not generally regarded as a stress
      provoking experience, chiropractors should actively screen their patients for
      evidence of stress and take steps to enhance their patients' perceptions of the
      chiropractic consultation as a stress-free experience.

PMID- 9272471
TI  - An interactive model of chiropractic practice: reconstructing clinical reality.
AB  - OBJECTIVE: This study proposes an interactionist model of chiropractic care, uses
      practice observation to ascertain whether this framework is compatible with
      clinical reality and explores a novel explanation of how chiropractic clinical
      communication may contribute to healing. DESIGN: A constructivist inquiry
      paradigm based upon purposive sampling, grounded theory, inductive analysis and
      contextual interpretation was used. The compatibility of chiropractic clinical
      reality with an evolving interactionist model was ascertained through reflection
      on contemporary literature and practice observation of 208 consultations
      undertaken by 34 chiropractors working in geographically dispersed areas of
      Australia. Sample selection used a maximum variation strategy. Triangulation of
      data collected was undertaken by mailing the clinical communication scenario
      constructed by the investigator to participating chiropractors for comment and by
      having 144 patients complete a questionnaire. RESULTS: Interaction observed in
      chiropractic practice is bidirectional, is both task- and relationship-oriented,
      and seems to be verbal and nonverbal in nature. Touch, whether diagnostic or
      therapeutic, emerged as an fundamental feature of chiropractic care. CONCLUSION:
      Verbal and nonverbal communication in chiropractic practice, when analyzed within
      a interactionist framework, can be construed to create an environment conducive
      to healing by establishing a shared clinical reality. The ability of the
      consultation to change perceptions and reduce anxiety is presented as a
      substantial factor contributing to the potency of the chiropractic care. The
      interactionist model proposed for chiropractic care was found to provide a useful
      framework for reconceptualizing chiropractic clinical practice. By providing an
      additional perspective of chiropractic practice, this model enhances discourse on
      the variables contributing to the success of chiropractic care.

PMID- 9272472
TI  - The effectiveness of chiropractic management of fibromyalgia patients: a pilot
      study.
AB  - OBJECTIVE: To demonstrate the effectiveness of chiropractic management for
      fibromyalgia patients using reported pain levels, cervical and lumbar ranges of
      motion, strength, flexibility, tender points, myalgic score and perceived
      functional ability as outcome measures. DESIGN: A. Preliminary randomized control
      crossover trial. B. Before and after design. PATIENTS: Twenty-one rheumatology
      patients (25-70 yr). CHIROPRACTIC INTERVENTIONS: Treatment consisted of 4 wk of
      spinal manipulation, soft tissue therapy and passive stretching at the
      chiropractors' discretion. CONTROL INTERVENTION: Chiropractic management withheld
      for 4 wk with continuation of prescribed medication. MAIN OUTCOME MEASURES:
      Changes in scores on the Oswestry Pain Disability Index, Neck Disability Index,
      Visual Analogue Scale, straight leg raise and lumbar and cervical ranges of
      motion were observed. RESULTS: Chiropractic management improved patients'
      cervical and lumbar ranges of motion, straight leg raise and reported pain
      levels. These changes were judged to be clinically important within the confines
      of our sample only. CONCLUSIONS: Further study with a sample size of 81 (for 80%
      power at alpha < or = .05) is recommended to determine if these findings are
      generalizable to the target population of fibromyalgia suffers.

PMID- 9272473
TI  - Conservative management of spinal osteoarthritis with glucosamine sulfate and
      chiropractic treatment.
AB  - OBJECTIVE: To evaluate the rationale behind the most commonly used treatments of
      osteoarthritis, including nonsteroidal anti-inflammatory drugs (NSAIDs), and to
      assess more effective conservative treatment options. SUMMARY OF BACKGROUND DATA:
      This review includes a description of the pathophysiology and prevalence of
      osteoarthritis, joint physiology and NSAID treatment of osteoarthritis, as well
      as side effects on joints, the gastrointestinal tract, kidneys and livers.
      Several studies of conservative treatment, consisting of supplementation of
      glucosamine sulfate (which occurs naturally in the human body), exercise, and the
      use of chiropractic treatment for maintaining joint function and preventing
      further destruction, are reviewed. DATA SOURCES: A computerized search of Medline
      using the key indexing terms osteoarthritis, degenerative joint disease,
      nonsteroidal anti-inflammatory drugs, glucosamine sulfate, chiropractic and
      manipulation. RESULTS: Numerous studies wee obtained under each subheading and
      reviewed by category. Human and animal-model studies are described. CONCLUSION:
      The rationales for using NSAIDs in the treatment of osteoarthritis is
      controversial and openly contested. Given the detrimental effects of NSAIDs on
      joints and other organs, their use should be discouraged and their classification
      as a first choice conservative treatment should be abolished. A truly effective
      and conservative approach to the treatment of osteoarthritis should include
      chiropractic manipulation, essential nutrient supplementation, exogenous
      administration of glucosamine sulfate and rehabilitative stretches and exercises
      to maintain joint function. Because there is no correlation between pain levels
      and the extent of degeneration detected by radiographic or physical examination,
      conservative treatment should be initiated and sustained based on functional,
      objective findings and not strictly on how the patient feels. The use of NSAIDs
      should be limited to the treatment of gross inflammation and analgesics should
      only be used in the short-term when absolutely necessary for pain palliation. The
      present conservative approach could lead not only to a better quality of life but
      also to the saving of health care dollars by reducing the iatrogenic morbidity
      and mortality associated with NSAID use.

PMID- 9272474
TI  - Trigeminal neuralgia: sudden and long-term remission with transcutaneous
      electrical nerve stimulation.
AB  - OBJECTIVE: To discuss a case of trigeminal neuralgia that responded to an
      accidental high-intensity discharge of electrical current delivered by a
      transcutaneous electrical nerve stimulator (TENS). CLINICAL FEATURES: A 36-yr-old
      man suffering from a 5-month history of worsening paroxysmal pain of the left
      facial and temporal regions was referred to a neurologist by his family
      physician. A clinical diagnosis of trigeminal neuralgia was made; before
      committing to pharmaceutical treatment, however, the patient sought chiropractic
      consultation. INTERVENTION AND OUTCOME: A trial of self-applied TENS was
      recommended for pain control. Initial application to patient tolerance provided
      transient pain relief until an accidental, intense discharge resulted in
      immediate remission of symptoms, lasting now for three years. CONCLUSION: As an
      initial treatment of choice, TENS can be a safe and effective therapy for
      trigeminal neuralgia. The unique effect of this accidental application leads us
      to speculate that diffuse noxious inhibitory controls may have been the pain
      inhibitory pathway responsible for the resolution of symptoms in this case.
      Although firm conclusions are difficult to draw from one incident, using TENS at
      an intense, noxious level may improve its therapeutic efficacy by decreasing
      treatment time and frequency and eliciting long-lasting effects. This case
      suggests the need for further investigation of TENS in the treatment of
      trigeminal neuralgia and related pain syndromes.

PMID- 9272475
TI  - Anthropometrical and mechanical considerations in determining normal parameters
      for the sagittal lumbar spine.

PMID- 9272476
TI  - Chiropractic care for women with chronic pain: a prospective single-group
      intervention study.

PMID- 9272477
TI  - Signal transduction and protein kinases: the long way from the plasma membrane
      into the nucleus.
AB  - All living cells must be able to receive information from the extracellular space
      and to react to it by processing and converting it into intracellular effects. If
      the properties of cells are to change in the long term, some signals must reach
      the nucleus in order to bring about changes in gene transcription. Three of the
      pathways, beginning with an extracellular signal and ending with the nucleus,
      serve to illustrate some principles of signal transduction such as signal
      conversion, signal cascade, cross-talk, and on/off switch. One element common to
      most of the pathways is the activation of protein kinases. One example of these
      kinases, the protein kinase C, is discussed as a vehicle of signal transport
      toward the nucleus and as a means of cross-talk between different signaling
      pathways.

PMID- 9272478
TI  - Coiled bodies in hepatopancreas cells of shrimp infected with viruses and
      bacteria.

PMID- 9272479
TI  - Activation of protein kinase C (PKC) by 3,4-methylenedioxymethamphetamine (MDMA)
      occurs through the stimulation of serotonin receptors and transporter.
AB  - This report further characterizes the intermediate metabolic effects of the
      psychotropic amphetamine derivative, 3,4-methylenedioxymethamphetamine (MDMA or
      "ecstasy"), on the activity of second messenger-dependent kinases. Previous work
      has demonstrated that two injections of MDMA (20 mg/kg) elicits a prolonged
      translocation of the calcium and phospholipid-dependent enzyme, protein kinase C
      (PKC) in rats. However, because MDMA has actions at the 5-HT transporter and 5
      HT2A/2C receptors, our experiments were directed at uncovering which of these
      many sites may be involved in this second messenger dependent response. A single
      injection of MDMA produced a time- and dose-dependent increase in the density of
      cortical and hippocampal PKC (as measured by 3H-phorbol 12,13-dibutyrate (PDBu)
      binding sites. MDMA-mediated PKC translocation was long-lasting and remained
      above control (saline-treated rats) for up to 24 h after injection. This effect
      was mimicked by another substituted amphetamine, p-chloroamphetamine (pCA), but
      with a temporal-response curve that was to the left of MDMA's. However, pure
      uptake inhibitors like fluoxetine, cocaine, and the selective 5-HT2A/2C agonist,
      DOB, were unable to produce a long-lasting translocation of PKC binding sites in
      rat cortex. Fluoxetine, a selective serotonin uptake inhibitor (SSRI) and
      ketanserin a 5-HT2A antagonist, attenuated PKC translocation by MDMA with
      differing efficacies; however, both compounds completely prevented the loss of 5
      HT uptake sties after multiple doses of MDMA. These results suggest that MDMA
      increases PKC translocation by two interrelated mechanisms that involve 5-HT2A/2C
      receptors and the 5-HT transporter. This pathway appears to include: (1) the drug
      binding to the 5-HT transporter, (2) the release of cytosolic 5-HT stores into
      the extracellular space, and (3) the activation of post-synaptic 5-HT2A/2C
      receptors linked to G-protein-mediated phospholipid hydrolysis.

PMID- 9272480
TI  - Time-dependent effects of repeated amphetamine treatment on norepinephrine in the
      hypothalamus and hippocampus assessed with in vivo microdialysis.
AB  - The effects of repeated amphetamine (AMPH) pretreatment on norepinephrine (NE)
      neurotransmission in the hypothalamus and hippocampus were assessed using in vivo
      microdialysis. Rats were pretreated with either saline or an escalating-dose AMPH
      regimen (1-->10 mg/kg) over 10 consecutive days, and then were withdrawn from
      AMPH for either 1 day or 30 days, at which time the animals underwent two
      consecutive days of testing. As expected, repeated treatment with AMPH resulted
      in time-dependent changes in both spontaneous locomotor activity and in the
      psychomotor response to a subsequent challenge injection of AMPH. In addition,
      repeated exposure to AMPH resulted in time-dependent and regionally-specific
      changes in the basal concentrations of NE in dialysate, and in the NE response to
      an AMPH challenge. For example, AMPH pretreatment produced a persistent (at least
      one month) increase in the basal concentration of NE in the hippocampus, but not
      the hypothalamus, although the response to an AMPH challenge was altered in both
      structures. It is suggested that AMPH treatment produces adaptations in NE
      systems that far outlast the acute effects of the drug, and that these may
      contribute to both transient and more persistent behavioral sequelae associated
      with the discontinuation of chronic AMPH use.

PMID- 9272481
TI  - Ketamine-induced exacerbation of psychotic symptoms and cognitive impairment in
      neuroleptic-free schizophrenics.
AB  - The N-methyl-d-aspartate (NMDA) receptor has been implicated in the
      pathophysiology of schizophrenia. We administered subanesthetic doses of the NMDA
      receptor antagonist ketamine in a double-blind, placebo-controlled design to 13
      neuroleptic-free schizophrenic patients to investigate if schizophrenics will
      experience an exacerbation of psychotic symptoms and cognitive impairments with
      ketamine. We also examined whether schizophrenics experienced quantitative or
      qualitative differences in ketamine response in comparison to normal controls.
      Schizophrenics experienced a brief-ketamine-induced exacerbation of positive and
      negative symptoms with further decrements in recall and recognition memory. They
      also displayed greater ketamine-induced impairments in free recall than normals.
      Qualitative differences included auditory hallucinations and paranoia in patients
      but not in normals. These data indicate that ketamine is associated with
      exacerbation of core psychotic and cognitive symptoms in schizophrenia. Moreover,
      ketamine may differentially affect cognition in schizophrenics in comparison to
      normal controls.

PMID- 9272482
TI  - Chronic nicotine enhances basal and nicotine-induced Fos immunoreactivity
      preferentially in the medial prefrontal cortex of the rat.
AB  - In the present study, expression of the immediate early gene protein products Fos
      and Jun-B within the dorsolateral striatum, the core and shell of the nucleus
      accumbens (NAC), the medial prefrontal cortex (mPFC), and the ventrolateral
      orbital cortex was examined. Rats were injected s.c. with either saline or
      nicotine (0.5 mg/kg) once daily for 12 days. On day 13, animals received a
      challenge injection of either saline or nicotine (0.5 or 1.0 mg/kg, s.c.) and 2 h
      later their brains were examined for Fos-like (FLI) and Jun-B-like (JLI)
      immunoreactivity. Chronic nicotine significantly increased basal expression of
      FLI selectively in the mPFC. Nicotine challenge significantly increased FLI in
      the mPFC of saline-treated animals and even further increased FLI in the mPFC of
      nicotine-treated animals. In the shell of the NAC, nicotine challenge also
      increased FLI in nicotine-treated animals, whereas it increased JLI only in
      saline-treated animals. After chronic nicotine treatment, injection of D1
      receptor antagonist SCH 23390 (0.1 mg/kg, i.p.) 10 min before a nicotine
      challenge (0.5 mg/kg, s.c.), significantly attenuated the nicotine-induced FLI in
      the mPFC and the shell of the NAC. These results suggest that the regionally
      selective effect of nicotine challenge on FLI is due to enhanced dopaminergic
      transmission, mediated via stimulation of D1 receptors.

PMID- 9272483
TI  - Imaging D2 receptor occupancy by endogenous dopamine in humans.
AB  - The impact of endogenous dopamine on in vivo measurement of D2 receptors in
      humans was evaluated with single photon emission computerized tomography (SPECT)
      by comparing the binding potential (BP) of the selective D2 radiotracer
      [123I]IBZM before and after acute dopamine depletion. Dopamine depletion was
      achieved by administration of the tyrosine hydroxylase inhibitor alpha-methyl
      para-tyrosine (AMPT), given orally at a dose of 1 g every six hours for two days.
      AMPT increased [123I]IBZM BP by 28 +/- 16% (+/- SD, n = 9). Experiments in
      rodents suggested that this effect was due to removal of endogenous dopamine
      rather than D2 receptor upregulation. Synaptic dopamine concentration was
      estimated as 45 +/- 25 nM, in agreement with values reported in rodents. The
      amplitude and the variability of the AMPT effect suggested that competition by
      endogenous dopamine introduces a significant error in measurement of D2 receptors
      in vivo with positron emission tomography (PET) or SPECT. However, these results
      also imply that D2 receptor imaging coupled with acute dopamine depletion might
      provide estimates of synaptic dopamine concentration in the living human brain.

PMID- 9272484
TI  - Time course of 5-HT2A receptor occupancy in the human brain after a single oral
      dose of the putative antipsychotic drug MDL 100,907 measured by positron emission
      tomography.
AB  - MDL 100,907 is a potent and selective antagonist of 5-HT2A serotonin receptors.
      Animals studies suggest that MDL 100,907 may behave as an atypical antipsychotic
      drug. Positron emission tomograph (PET) using [11C]NMSP as the radiotracer was
      used to define the time course of 5-HT2 receptor occupancy in the human frontal
      cerebral cortex after a single oral dose of MDL 100,907 (10 or 20 mg) in nine
      healthy subjects. After the baseline scan each subject was studied three times
      post dosing at various time points. 5-HT2 occupancies were in the range of 70 and
      90% after each dose. While the occupancy remains in this range over 24 hours
      after 20 mg MDL 100,907, it decreases by about 20% at 24 hours compared to the
      timepoint at 8 hours, when only 10 mg are administered (p < 0.05). Our results
      should allow determination of the appropriate dosing regimen for future trials in
      schizophrenic patients.

PMID- 9272485
TI  - Long-term effects of S(+)N-n-propylnorapomorphine compared with typical and
      atypical antipsychotics: differential increases of cerebrocortical D2-like and
      striatolimbic D4-like dopamine receptors.
AB  - Changes in D2-like dopamine (DA) receptor binding in rat brain regions were
      compared by quantitative in vitro receptor autoradiography after 21-d treatment
      with a typical (fluphenazine), atypical (clozapine), or candidate atypical
      antipsychotic (S[+]-N-n-propylnorapomorphine, [+]-NPA). Fluphenazine treatment
      significantly increased binding of the D2,3,4 radioligands [3H]nemonapride and
      [3H]spiperone in caudate-putamen (CPu: 22%, 32%), nucleus accumbens (ACC: 67%,
      52%), olfactory tubercle (OT: 53%, 43%), and medial prefrontal cerebral cortex
      (MPC: 46%, 47%) but not dorsolateral frontal cortex (DFC). D2-like binding in MPC
      was also increased by (+)-NPA (49%, 39%) and clozapine (60%, 40%), but not in
      DFC, CPu, ACC, or OT. Binding of D2,3-selective [3H]raclopride increased less
      after fluphenazine in ACC (27%) and CPu (16%) than with the nonselective
      radioligands, and not after clozapine or (+)-NPA. D3-selective binding of [3H]R
      (+)-7-OH-DPAT was not changed with any treatment or region including islands of
      Calleja. Binding of [3H]nemonapride or [3H]spiperone under D4-selective
      conditions (with 300 nM S[-]-raclopride and other masking agents, at sites
      occluded by D4 ligand L-745,870), was increased by fluphenazine, (+)-NPA,
      clozapine in ACC (120%, 76%, 70%, respectively), and CPu (54%, 37%, 35%), but not
      in OT, DFC or MPC. These results support the hypothesis that cerebrocortical D2
      like and striatolimbic D4-like receptors contribute to antipsychotic actions of
      both typical and atypical drugs and encourage further consideration of
      S(+)aporphines as potential atypical antipsychotics.

PMID- 9272486
TI  - The putative atypical antipsychotic drug amperozide preferentially increases c
      fos expression in rat medial prefrontal cortex and lateral septum.
AB  - The effects of acute, systemic administration of the putative atypical
      antipsychotic drug amperozide on c-fos expression in the rat forebrain were
      studied by means of Fos immunohistochemistry. Amperozide significantly increased
      the number of Fos-immunoreactive nuclei in the medial prefrontal cortex and the
      lateral septum but not in the nucleus accumbens (shell or core), the striatum, or
      the amygdala. With the exception of the nucleus accumbens-shell, where amperozide
      failed to produce statistically significant increases, the regional distribution
      of Fos immunoreactivity following amperozide was similar to that induced by
      atypical, but not by typical, antipsychotic drugs. In addition, after amperozide
      the number of Fos-positive nuclei was higher in the nucleus accumbens than in the
      dorsolateral striatum, a characteristic that is common to all known atypical
      antipsychotic agents.

PMID- 9272487
TI  - Reversal of phencyclidine-induced hyperactivity by glycine and the glycine uptake
      inhibitor glycyldodecylamide.
AB  - Phencyclidine (PCP) induces a psychotic state that closely resembles
      schizophrenia. In preclinical studies, PCP has been shown to induce its unique
      behavioral effects by blocking excitatory neurotransmission mediated at the N
      methyl-D-aspartate (NMDA) receptors, suggesting that agents which potentiate NMDA
      receptor-mediated neurotransmission might have clinically beneficial effects. The
      present study demonstrates that the NMDA co-agonist glycine inhibits rodent
      hyperactivity induced by PCP, but not amphetamine. Glycyldodecylamide, a compound
      that blocks neuronal glycine uptake and which may therefore increase
      intrasynaptic glycine levels, inhibits PCP-induced hyperactivity more potently
      than glycine. These results complement recent clinical studies with glycine and
      suggest that glycine-uptake inhibitors, as well as glycine, may be beneficial in
      the treatment of PCP-induced psychosis and schizophrenia.

PMID- 9272488
TI  - MRI of the brain in neurologically healthy middle-aged and elderly individuals.
AB  - Our purpose was to document the MRI appearances of the brain in healthy middle
      aged to elderly subjects. T2- and proton density-weighted axial slices were
      obtained in 61 volunteers, 30-86 years of age. After visual inspection, signal
      intensities of brain structures were measured on T2-weighted images. Age-related
      changes became increasingly apparent after age 50. The main findings were that
      signal intensity of the white matter increased concomitantly with widening of the
      cerebrospinal fluid spaces; that basal ganglia remained stable; that high-signal
      foci in white matter increased in number and size after the age of 50 years; that
      periventricular high-signal foci were constant after the age of 65 years. Our
      visual impression of a decrease in signal intensity of the central grey matter
      with age seems to be mistaken. Pathological processes should be suspected if
      periventricular foci are found in middle-aged or young subjects.

PMID- 9272489
TI  - Brain MR imaging in patients with hepatic cirrhosis: relationship between high
      intensity signal in basal ganglia on T1-weighted images and elemental
      concentrations in brain.
AB  - In patients with hepatic cirrhosis, the globus pallidus and putamen show high
      intensity on T1-weighted MRI. While the causes of this high signal have been
      thought to include paramagnetic substances, especially manganese, no evidence for
      this has been presented. Autopsy in four cases of hepatic cirrhosis permitted
      measurement of metal concentrations in brain and histopathological examination.
      In three cases the globus pallidus showed high intensity on T1-weighted images.
      Mean manganese concentrations in globus pallidus, putamen and frontal white
      matter were 3.03 +/- 0.38, 2.12 +/- 0.37, and 1.38 +/- 0.24 (micrograms/g wet
      weight), respectively, being approximately four- to almost ten-fold the normal
      values. Copper concentrations in globus pallidus and putamen were also high, 50%
      more than normal. Calcium, iron, zinc and magnesium concentrations were all
      normal. The fourth case showed no abnormal intensity in the basal ganglia and
      brain metal concentrations were all normal. Histopathologically, cases with
      showing high signal remarkable atrophy, necrosis, and deciduation of nerve cells
      and proliferation of glial cells and microglia in globus pallidus.. These
      findings were similar to those in chronic manganese poisoning. On T1-weighted
      images, copper deposition shows no abnormal intensity. It is therefore inferred
      that deposition of highly concentrations of manganese may caused high signal on
      T1-weighted images and nerve cell death in the globus pallidus.

PMID- 9272490
TI  - MRI of the fornix and mamillary body in temporal lobe epilepsy.
AB  - We performed MRI on 27 patients with clinically proven temporal lobe epilepsy
      (TLE), all with prior EEG lateralisation, and 10 volunteers, studied to evaluate
      disparity in size arising from biological variation (group 1). Three-dimensional
      spoiled GRASS (3DSPGR) sequences provided 2-mm contiguous sections of the limbic
      system, enabling assessment of the hippocampus (HC), fornix (FN) and mamillary
      body (MB). Measurements of FN and MB width were made from a workstation. Any
      percentage difference in size was computed. In 19 cases there was unilateral
      abnormality in the HC (group 2); in 18 and 19 cases respectively there was a
      smaller FN and MB on the same side as the abnormal HC. This percentage difference
      in size was significantly greater than that in group 1 in the FN and MB in 17 and
      17 cases respectively. Comparison of percentage difference computations for FN
      and MB between groups 1 and 2 showed high statistical significance (P < 0.0002).
      In 5 patients with clinical TLE the HC was normal on MRI (group 3). Unequal FN
      and MB sizes were found in 4, significant in 2. Comparison of percentage
      difference computations for FN and MB showed statistical significance (P < 0.0005
      and P < 0.0003 respectively). There was no case of discordance between the sides
      of hippocampal abnormality and the smaller FN or MB or between the sides of
      smaller FN and MB. The strong concordance between the changes in the HC and those
      in the FN and MB suggests that this combination will play an important role in
      the assessment of TLE and limbic system abnormality.

PMID- 9272491
TI  - Imaging in primary progressive aphasia.
AB  - Primary progressive aphasia (PPA) presents with aphasia, with or without other
      minor cognitive dysfunction. We report five patients with PPA to show the
      correlation between their clinical signs and imaging findings. The patients can
      be divided into those with nonfluent (group 1) and those with fluent (group 2)
      aphasia. The characteristic speech impairment was bradylalia in group 1 and word
      amnesia in group 2. Impairment of comprehension was common but mild in both
      groups. On MRI, patients in group 1 showed predominantly left frontal and
      perisylvian atrophy with reduced uptake in the same region on single photon
      emission computed tomography (SPECT) using technetium-99m hexamethyl
      propyleneamine oxime (99mTc HMPAO). Patients in group 2 showed left temporal
      atrophy involving the superior, middle and inferior temporal gyri, hippocampus
      and parahippocampal gyrus on MRI and reduced uptake in the same region on SPECT.
      These findings correlated well with the functional anatomy of speech impairment.

PMID- 9272492
TI  - Metabolic and neurological patterns in chronic cerebral infarction: a single
      voxel 1H-MR spectroscopy study.
AB  - The details of brain metabolism in chronic cerebral infarcts have not been
      clarified. Using proton MR spectroscopy (1H-MRS) at 1.5 T, we measured
      biochemical changes in 16 patients with large infarcts involving the motor cortex
      in the chronic phase (median 293.9 days) and related the findings to clinical
      data. Localised spectra were obtained using point-resolved spectroscopy, with an
      echo time of 270 ms. Regions of interest were placed on the frontal lobe,
      including the precentral gyrus and central sulcus. Motor function was assessed by
      the manual muscle power test at the time of the 1H-MRS study. Only three patients
      with severe paresis had no signal in the lesions and a lactate signal was
      obtained in 13 cases. N-acetyl aspartate (NAA) was observed in 4 cases with
      recanalisation of an occluded vessel. Motor function correlated strongly with the
      NAA/choline-containing compounds (Cho) ratio (P < 0.01) and lactate/Cho ratio (P
      < 0.01). We found various metabolic patterns, reflecting residual neurological
      function.

PMID- 9272493
TI  - Problems in the diagnosis of intracranial venous infarction.

PMID- 9272494
TI  - MRI of intracranial chordomas. Extent of tumour and contrast enhancement:
      criteria for differential diagnosis.
AB  - We present six proven cases of chordoma of the clivus studied by CT and MRI, with
      special attention to the extent of the tumour and to the signal intensity after
      intravenous gadolinium. MRI is the best technique for assessing the extent of the
      tumour but CT is important for showing osteolysis. Our aim was to determine
      differential diagnostic neuroradiological criteria. Reliable signs of chordoma of
      the skull base are: posterior extension to the pontine cistern; a lobulated,
      "honeycomb" appearance after gadolinium: the swollen appearance of the bone in
      the early stages; bone erosion on CT and frequent extension to critical
      structures such as the circle of Willis, cavernous sinuses and brain stem.

PMID- 9272495
TI  - "Dural tail" adjacent to a giant posterior cerebral artery aneurysm: case report
      and review of the literature.
AB  - The "dural tail" sign on gadolinium (Gd-DTPA)-enhanced MRI has been described in
      association with meningiomas. Various series with histopathological correlation
      have shown that in some cases there is tumour invasion into the dura mater, but
      in the majority of cases it represents a hypervascular, non-neoplastic reaction.
      While this sign was originally thought to be specific for meningioma, subsequent
      case reports have described the presence of a dural tail in other intra- and
      extra-axial lesions. We present a patient with a giant aneurysm arising from the
      P2 segment of the right posterior cerebral artery, adjacent to the tentorium,
      with a prominent dural tail on Gd-DTPA-enhanced MRI. In this location,
      differentiation of an aneurysm from a meningioma was critical.

PMID- 9272496
TI  - Dense Rhodococcus cerebral abscesses in an HIV-positive patient.
AB  - Rhodococcus equi, formerly known as Corynebacterium equi, an aerobic, gram
      positive, pleomorphic coccobacillus, is a well-known pathogen for domestic
      livestock. We present a biopsy- and culture-proven case of Rhodococcus equi brain
      abscesses in a patient seropositive for HIV, having an appearance not described
      previously.

PMID- 9272497
TI  - MRI of cervical facet dislocation.
AB  - The MRI examinations of eight patients with cervical vertebral dislocation
      demonstrated by conventional radiography were reviewed. All patients had axial
      and sagittal T1- and T2-weighted imaging on a 1.5-T Unit. This revealed
      unilateral partial facet dislocation (in two patients), bilateral partial facet
      dislocation (in two), unilateral complete dislocation (in two) and bilateral
      complete facet dislocation (in two). In six patients there was cord contusion,
      three had focal disc protrusions and four unilateral absence of normal flow void
      in one of the cervical vertebral arteries. In all cases, the dislocated facets
      were shown well on the far-lateral sagittal images.

PMID- 9272498
TI  - MRI of the postoperative lumbar spine: triple-dose gadodiamide and fat
      suppression.
AB  - In ten patients who had undergone lumbar laminectomy, visual assessment of
      epidural scar enhancement and diagnostic confidence was performed after 0.1
      mmol/kg gadodiamide intravenously, again after a further 0.2 mmol/kg, and once
      more using a fat-suppression sequence. The single-dose contrast-enhanced T1
      weighted images showed clear enhancement of epidural scar in eight cases, and
      clearly improved diagnostic confidence as regards scar and/or disc herniation in
      six. Triple-dose contrast-enhanced images showed further increase in epidural
      enhancement clearly in only two cases and marginally in six, with no significant
      increase in diagnostic confidence. Fat-suppression, performed in eight cases,
      showed a further clear increase in epidural enhancement in seven cases, but again
      no increase in diagnostic confidence. In one patient with arachnoiditis contrast
      enhancement and diagnostic confidence increased only slightly after each contrast
      injection, and again with the fat-suppression sequence. Increasing contrast
      medium dose was thus not useful following laminectomy when epidural scarring
      obscures a possible recurrent disc herniation. Use of fat suppression may,
      however, permit reduction of the dose of contrast medium necessary to provide
      adequate scar enhancement.

PMID- 9272499
TI  - MRI screening for acoustic neuroma without gadolinium: value of 3DFT-CISS
      sequence.
AB  - To evaluate the efficacy of a gradient-echo sequence (3DFT-CISS) in the diagnosis
      of acoustic neuromas, two independent observers twice reviewed the images of the
      temporal bones of 83 patients. Contrast-enhanced T1-weighted spin echo images
      were used as the reference, showing 18 acoustic neuromas, including 5 purely
      intracanalicular and one intralabyrinthine tumours. High sensitivity (89-94%),
      specificity (94-97%) and accuracy (94-95%) were found. Intraobserver (kappa 0.93
      1) and interobserver (kappa 0.83-0.84) reproducibility were very good. The
      smallest intracanalicular tumour was overlooked twice by both observers; the
      intralabyrinthine tumour once by one observer. All tumours were detected with a
      less stringent decision criterion, at the expense of lower specificity.

PMID- 9272500
TI  - The size of acoustic neuromas: CT and MRI.
AB  - The growth rate of acoustic neuromas is very variable: some tumours grow rapidly,
      some do not grow and some even get smaller. When making treatment decisions, it
      may be important to have an idea of the growth rate of the individual tumour, and
      this is only possible when there are comparable examinations. We performed both
      CT and MRI on 15 patients. Two radiologists estimated the size of their acoustic
      neuromas. There was a significant difference between the two examiners'
      calculations of tumour volumes on CT and between the first examiner's CT and MRI
      volume calculations. No difference was found between the two MRI volume
      estimations or the second examiner's estimation of volumes on CT and MRI.
      Measurements of the maximal tumour diameter along the pyramid showed good
      concordance. We conclude that measurement the size of acoustic neuromas is
      reproducible with MRI and the measurement of the maximal tumour diameter is in
      practice a better parameter for comparison than calculation of real volume.

PMID- 9272501
TI  - Unilateral medial dislocation of the temporomandibular joint.
AB  - We present our experience of the rare condition of unilateral medial dislocation
      of the temporomandibular joint (TMJ) in 11 patients with head trauma who had
      received a direct lateral blow on the chin. The diagnosis was made by direct
      coronal CT of the TMJ performed from 6 h to 7 days following the injury. In 6
      patients, subcondylar fracture of the ipsilateral mandibular ramus was also
      demonstrated. A second CT performed 11-16 months following the first one
      demonstrated pseudoarthrosis of the fractured ramus in these 6 patients. The
      second CT was identical to the first in the remaining 5 patients with pure
      dislocation of the condyle. All patients suffered from severe disability of the
      TMJ. The maximal vertical distance between the upper and lower incisors in
      patients with uncomplicated dislocation ranged between 8 and 12 mm. In cases with
      complicated medial condylar dislocation with fracture and pseudoarthrosis of the
      mandibular ramus, this distance ranged between 16 and 25 mm, probably because of
      additional movement in the area of the pseudoarthrosis. The maximal vertical
      distance between the incisors was compared with a control group of 20 normal
      adults who had values from 40 to 52 mm. Medial unilateral dislocation of the TMJ
      can appear in two forms: uncomplicated or complicated, with pseudoarthrosis of
      the ipsilateral mandibular ramus.

PMID- 9272502
TI  - MRI of a family with focal abnormalities of gyration.
AB  - Focal abnormalities of gyration (FAG) are developmental disorders that may occur
      in isolated patients or, as in the case being reported, as part of a familial
      disorder. Analysis of individuals in a family spanning three generations was
      carried out using MRI. Abnormalities, present in all members of generations II
      and III, included focal cortical dysplasia (three patients), focal cortical
      infolding (two patients) and schizencephaly (one patient); associated minor
      anomalies, such as white matter abnormalities, were seen in the remaining three
      members of generations II and III. MRI recognition of FAG in the family being
      reported proved useful in defining their phenotypical expression and providing
      proper counselling for individual family members.

PMID- 9272503
TI  - Pathophysiological mechanisms underlying vasovagal syncope in young subjects.
AB  - The occurrence of vasovagal fainting is common in young subjects, but the origin
      of the precipitating hemodynamic mechanisms involved remain a subject of
      considerable speculation. Vasovagal fainting is not a sudden onset phenomenon,
      early failure of vascular resistance responses occurs in faint-prone young
      subjects. The variability of hemodynamic responses during the actual faint is
      large, but the main mechanism operative during, is withdrawal of sympathetic
      outflow to blood vessels in skeletal muscle with impairment of ability to
      maintain vasomotor tone.

PMID- 9272504
TI  - Bedside autonomic function testing in patients with vasovagal syncope.
AB  - The factors that determine the individual susceptibility to vasovagal syncope
      (VVS) are largely unknown, including the role of the autonomic nervous system. We
      therefore studied common vagal and sympathetic reflexes in 12 patients with VVS
      (mean age 37 (18-75) years, 6 men). The Valsalva maneuver and deep breathing were
      performed to assess vagal responsiveness and mental arithmetic stress; the cold
      pressor test and isometric handgrip were performed to assess sympathetic
      responsiveness. Standing up was performed to assess the combined responsiveness.
      With the exception of a subnormal response to deep breathing in one patient, all
      vagal tests were normal. In contrast, the response to mental stress, the cold
      pressor test, and isometric handgrip was subnormal in 4 patients, 6 patients, and
      4 patients, respectively. The response to standing up was normal in all patients.
      It is concluded that many patients with VVS are characterized by normal vagal
      responsiveness, but sympathetic hyporesponsiveness. Sympathetic
      hyporesponsiveness might explain the inadequate vasoconstruction, which plays an
      important, early role in VVS.

PMID- 9272505
TI  - Unexplained syncope: clinical management.
AB  - The management of unexplained syncope begins with the patient's history and
      physical examination, which are oriented to help separate benign from serious
      causes. Malignant etiologies are more likely to occur with exertional syncope.
      Cardiac causes should be considered, particularly cardiomyopathy, postoperative
      congenital heart disease, right ventricular dysplasia, anomalous coronary artery,
      pulmonary artery hypertension, myocarditis, long QT syndrome, and Wolff-Parkinson
      White syndrome. Neurological and metabolic disorders may underlie a syncope
      episode. After malignant causes of syncope have been excluded and the diagnosis
      of neurocardiac syncope has been established, treatment strategies include
      behavior modification, salt and increased fluids, and pharmacological agents.
      Efficacious agents include beta-blockers, dysopyramide, fludrocortisones, and
      alpha agents. Yet, behavior modification alone may be as effective as salt or
      pharmacological therapy. Because the natural history of neurocardiac syncope in
      children is spontaneous resolution, it is appropriate to try the simple measures
      before introducing drug therapy.

PMID- 9272506
TI  - Ion channels, the QT interval, and arrhythmias.
AB  - Aberrations in genes encoding for ion channels have been shown to underlie a
      number of cardiac arrhythmia syndromes, hitherto classified as idiopathic. These
      aberrations, inherited and congenital, may lead to dysfunction of channels with
      resultant abnormal current characteristics. In addition, a variety of stimuli may
      cause altered expression of these genes. Because prolongation of the action
      potential (and the QT-interval) is often the result, patients are at risk for the
      occurrence of arrhythmias based on reentry and the development of abnormal
      impulse initiation. Molecular dissection of the inherited syndromes has led to
      rapid progress in our understanding of basic knowledge about ion channel function
      and its relation to channel structure. This progress is undoubtedly of benefit
      for the understanding of the repolarization changes in more common conditions and
      will become of benefit to many more patients who suffer from therapy resistant
      arrhythmias.

PMID- 9272507
TI  - Molecular biology of the long QT syndrome: impact on management.
AB  - The long QT syndrome (LQTS) is a familial disease characterized by prolonged
      ventricular repolarization and high incidence of malignant ventricular
      tachyarrhythmias often occurring in conditions of adrenergic activation.
      Recently, the genes for the LQTS inked to chromosomes 3 (LQT3), 7 (LQT2), and 11
      (LQT1) were identified as SCN5A, the cardiac sodium channel gene and as HERG and
      KvLQT1 potassium channel genes. These discoveries have paved the way for the
      development of gene-specific therapy for these three forms of LQTS. In order to
      test specific interventions potentially beneficial in the molecular variants of
      LQTS, we developed a cellular model to mimic the electrophysiological
      abnormalities of LQT3 and LQT2. Isolated guinea pig ventricular myocytes were
      exposed to anthopleurin and dofetilide in order to mimic LQT3 and LQT2,
      respectively. This model has been used to study the effect of sodium channel
      blockade and of rapid pacing showing a pronounced action potential shortening in
      response to Na+ channel blockade with mexiletine and during rapid pacing only in
      anthopleurin-treated cells but not in dofetilide-treated cells. Based on these
      results we tested the hypothesis that QT interval would shorten more in LQT3
      patients in response to mexiletine and to increases in heart rate. Mexiletine
      shortened significantly the QT interval among LQT3 patients but not among LQT2
      patients. LQT3 patients shortened their QT interval in response to increases in
      heart rate much more than LQT2 patients and healthy controls. These findings
      suggest that LQT3 patients are more likely to benefit from Na+ channel blockers
      and from cardiac pacing because they are at higher arrhythmic risk at slow heart
      rates. Conversely, LQT2 patients are at higher risk to develop syncope under
      stressful conditions, because of the combined arrhythmogenic effect of
      catecholamines with the insufficient adaptation of their QT interval. Along the
      same line of development of gene-specific therapy, recent data demonstrated that
      an increase in the extracellular concentration of potassium shortens the QT
      interval in LQT2 patients suggesting that intervention aimed at increasing
      potassium plasma levels may represent a specific treatment for LQT2. The
      molecular findings on LQTS suggest the possibility of developing therapeutic
      interventions targeted to specific genetic defects. Until definitive data become
      available, antiadrenergic therapy remains the mainstay in the management of LQTS
      patients, however it may be soon worth considering the addition of a Na+ channel
      blocker such as mexiletine for LQT3 patients and of interventions such as K+
      channel openers or increases in the extracellular concentration of potassium for
      LQT1 and LQT2 patients.

PMID- 9272508
TI  - Clinical management of patients with the long QT syndrome: drugs, devices, and
      gene-specific therapy.
AB  - The familial long QT syndrome (LQTS) is now recognized as a genetic channelopathy
      with a propensity to arrhythmogenic syncope and sudden death. Three genetic
      mutations have been identified that involve the slow and fast delayed potassium
      rectifier currents and the sodium current. Distinctive ECG-T wave phenotypes are
      associated with each of the three genotypes. Current day therapy includes: beta
      adrenergic blocking drugs; pacemakers; left cervicothoracic sympathetic
      ganglionectomy; implanted cardioverter defibrillators; and possibly, drugs that
      improve mutant ionic channel dysfunction. LQTS has provided unique insight into
      the complex relationship between ionic channel dysfunction and ventricular
      tachyarrhythmias.

PMID- 9272509
TI  - Ventricular tachycardia in neonates.
AB  - Infant VT can be a devastating arrhythmia, with high mortality for those
      presenting with myocarditis, long QT syndrome, or cardiovascular collapse with
      rapid VT due to tumors. While management of these patients can be challenging and
      discouraging, other infants with wide QRS rhythms tend to follow a more benign
      course. These latter patients have accelerated idiopathic ventricular rhythm or
      aberrant forms of infant supraventricular tachycardia. Distinguishing these forms
      of wide QRS tachycardia from the more lethal forms is paramount to institution of
      appropriate therapies.

PMID- 9272510
TI  - Polymorphous ventricular tachyarrhythmias in the absence of structural heart
      disease.
AB  - Polymorphous ventricular tachyarrhythmias (PVTA) in the absence of structural
      heart disease form a particularly important target for comprehensive research.
      They occur in young, healthy children and young adults and most probably cover
      several underlying electrophysiological abnormalities. We individualized two
      syndromes, namely catecholaminergic ventricular tachyarrhythmias, and torsade de
      pointes (TDP) with a short coupling interval, but these two entities certainly
      represent only a part of the problem of idiopathic ventricular fibrillation.
      Having the implanted defibrillator as a therapeutic umbrella for those patients
      who were fortunate enough to escape from sudden death is not sufficient. Too
      often in modern cardiology the therapeutic achievements tend to precede the
      process of diagnosis and comprehension. At least, the former should not preclude
      the latter, a situation that can be observed, for instance, when the favorable
      effect of a drug is evidenced before its mode of action was understood. At best,
      both progress together, provided we pay attention to adequately exploit the
      resources of modern technology.

PMID- 9272511
TI  - Radiofrequency catheter ablation of idiopathic ventricular tachycardias in
      children.
AB  - We performed radiofrequency catheter ablation of idiopathic ventricular
      tachycardia in six children. In four, the ventricular tachycardia originated in
      the left ventricle, in two it originated in the right ventricular outflow tract.
      In 5/6 (83%) the RF procedure was successful; there were no complications.

PMID- 9272513
TI  - Radiofrequency ablation of accessory pathways associated with congenital heart
      disease.
AB  - The coexistence of significant congenital cardiac disease with accessory pathways
      is not uncommon, and presents a number of issues for clinical management. These
      issues include the propensity of such patients to have poorly tolerated
      tachycardia; the difficulties in choosing appropriate medical management given
      potential problems with preexisting sinus node disease, poor contractility, and
      the possibility of proarrhythmia; the need to seriously consider ablation prior
      to, or at the time of, intracardiac repair of congenital cardiac defects; and
      finally, the difficulties that complex anatomy may pose to the interventional
      electrophysiologist. Definitive management requires expertise both in
      electrophysiology and in pediatric cardiology. Success can usually be achieved
      with a careful, anatomically precise approach, combined with imagination and
      persistence. Because of the difficulties with medical management, catheter
      ablation may be the most attractive modality for control of accessory pathway
      tachycardia in this patient population.

PMID- 9272512
TI  - Anatomy of the atrioventricular junctions with regard to ventricular
      preexcitation.
AB  - In the normal heart, the atrioventricular junctions surround the orifices of the
      mitral and tricuspid valves. The septal area of the junctions is much smaller
      than generally thought, being made up of the fibrous membranous septum and the
      muscular atrioventricular septum. The left atrioventricular junction gives the
      potential for muscular atrioventricular contiguities only in relation to the
      mural leaflet of the mitral valve. The right junction extends from the area
      posterior to the muscular atrioventricular septum to the supraventricular crest
      of the right ventricle. Anomalous pathways for conduction, which produce pre
      excitation, can be found anywhere within these atrioventricular junctions. The
      pathways usually are the muscular accessory connections responsible for the Wolff
      Parkinson-White syndrome, which can exist in the left, septal, or right
      junctions. Specific muscular connections are found in the presence of Purkinje
      cell tumors, diverticulums of the coronary sinus, or when taking origin from
      nodes of Kent at the acute margin of the ventricular mass. The latter connections
      are responsible for most examples of so-called Mahaim conduction, and are also
      described as atriofascicular tracts. The true Mahaim fibers are best described as
      nodoventricular or fasciculo-ventricular connections, while the pathway
      previously labelled as atriofascicular by the European Study Group is now best
      distinguished as an atrio-Hisian tract. The slow and fast pathways into the
      atrioventricular node are composed or ordinary atrial myocardium, the orientation
      of the fibers probably producing preferential conduction.

PMID- 9272514
TI  - The asymptomatic patient with the Wolff-Parkinson-White electrocardiogram.
AB  - Sudden death can be the first manifestation of the Wolff-Parkinson-White (WPW)
      syndrome. The underlying mechanism being atrial fibrillation with a very high
      ventricular rate, because of a short anterograde refractory period of the
      accessory atrioventricular pathway (AP), deteriorating into ventricular
      fibrillation. Information on the anterograde refractory period of the AP is
      therefore important to recognize asymptomatic people with the WPW ECG at risk for
      dying suddenly. Several noninvasive tests are available to identify the low risk
      patient. Decision making when to interrupt the AP in asymptomatic WPW patients
      not at low risk requires an invasive study to document the electrophysiological
      properties of the AP and to determine its exact location.

PMID- 9272515
TI  - Development of the conduction system of the heart.
AB  - The muscle cells forming the myocardium and the muscle cells forming the
      intestinal smooth muscle layers, are both derived from the visceral mesoderm. All
      cardiomyocytes display autorhythmicity, intercellular conduction via gap
      junctions, and contraction, irrespective whether they are derived from atrium,
      ventricle, node, or bundles. it is the anatomical arrangement of the distinct
      components that is responsible for the coordinate contraction wave over the
      heart. These very basic principles have been insufficiently appreciated in most
      studies on the development of the conduction system, by which it got unnoticed
      that the proper anatomical arrangement is, in essence, layed down very early in
      development in the cardiac tube. In this review we will summarize recent
      immunohistochemical studies that have permitted this appreciation.

PMID- 9272516
TI  - Immunological aspects of congenital atrioventricular block.
AB  - Isolated congenital heart block (CHB) in children is strongly associated with the
      occurrence of autoantibodies to Ro/SS-A and La/SS-B in the circulation of the
      mother. Although these antibodies are generally found in patients with
      generalized autoimmune diseases, they may also occur in symptomless mothers of
      CHB patients. It is thought that anti-Ro/SS-A and anti-La/SS-B may reach the
      fetal circulation via transplacental transport, starting around the 20th week of
      gestation. Although several hypotheses have been put forward, the exact mechanism
      through which these autoantibodies bind the fetal conduction system and elicit a
      local inflammatory response is still unclear. Also, the induction of the
      autoantibody response in the mother remains largely obscure, although a putative
      role of viral infection has been suggested. In this overview, the structure of
      the involved antigens will be discussed, followed by the nature of the
      antibodies. Recent data regarding the etiology of the anti-Ro/SS-A and anti-La/SS
      B response and the role of these autoantibodies in the pathogenesis of CHB will
      be presented.

PMID- 9272517
TI  - Natural history of congenital complete atrioventricular block.
AB  - An update of studies on the natural history of congenital complete AV block is
      presented. A risk for heart failure, syncope, and sudden death is present at any
      age including fetal life. Unfavorable prognostic signs in utero are low and
      decreasing ventricular rate (VR), hydrops, AV valve regurgitation, and low aortic
      flow velocity. Indications for pacing in infancy are congestive heart failure,
      ventricular rate < 55 beats/min in isolated block and < 65 beats/min with
      associated disease, prolonged OTc, syncope attacks, frequent ventricular ectopic
      beats, and alternating ventricular pacemakers. Indications for immediate pacing
      in childhood and adult life are syncope, presyncope, VR rates lower than median
      for age, periods of junctional exit block, prolongation of QTc and mitral
      regurgitation, and change of ventricular pacemaker. Pacing is recommended to all
      patients older than 15 years.

PMID- 9272518
TI  - VDD pacing in children with congenital complete heart block: advantages of a
      single pass lead.
AB  - A single pass lead for VDD pacing in complete heart block is well described in
      adults but there are only brief reports of its use in children. We used standard
      adult size single pass leads in ten children and adolescents aged 3.7-17.2 years
      (mean 9.9 years) and weighing 13.5-76 kg (mean 35.4 kg) with congenital complete
      heart block. One patient had coexisting congenital heart disease and had
      undergone surgery. A 2:1 atrioventricular block in one patient was presumed to be
      congenital in origin. In four patients, the VDD system was their first pacing
      system. In six of the patients, 1-4 previous systems had been used and
      simultaneous extraction of ventricular leads (6) and/or atrial leads (2) was
      performed. Four different types of lead were used: Brilliant IMP15Q (Vitatron);
      Brilliant + IMR15Q (Vitatron); CapSure 5032 (Medtronic); and Unipass 425-13
      (Intermedics) with four different generators: Saphir 600 (Vitatron); Saphir II
      620 (Vitatron); Thera VDD 8948 (Medtronic); and Unity 292-07 (Intermedics). All
      leads were introduced via a subclavian vein puncture and the atrial dipole was
      placed low in the right atrium to provide slack for further growth while
      maintaining atrial sensing. Ventricular thresholds ranged from 0.2-0.8 V. The
      minimal atrial amplitude was 0.7-4 mV and the maximum amplitude was 2.5-8 mV.
      There was one early microdisplacement and the lead was repositioned. Over a
      follow-up period ranging from 1-39 months (mean 20.4 months), all patients have
      maintained low ventricular pacing thresholds and adequate atrial signals for
      reliable pacing at rest and with exercise. During this time some have undergone
      considerable growth. The patient with coexisting congenital heart disease died
      suddenly at 3 years, but the pacing system had no fault at autopsy. The standard
      adult size single pass lead provides a simple means to enable reliable atrial
      synchronous ventricular pacing in growing children with complete heart block.

PMID- 9272519
TI  - Electrophysiology of "incisional" reentrant atrial tachycardia complicating
      surgery for congenital heart disease.
AB  - Intraatrial reentrant tachycardia, which occurs frequently in patients who have
      undergone corrective surgery for congenital heart disease, presents a challenge
      to successful management. Because the surgical repair sites are invariably
      critical to the development and maintenance of reentrant atrial tachycardia, we
      use the term "incisional reentry" to describe these arrhythmias. An understanding
      of the electrophysiology of such "incisional reentry," and techniques to identify
      a critical isthmus, are essential for successful ablation of these circuits. A
      critical isthmus may be identified by the presence of entrainment with concealed
      fusion. Confirmation that the site is critical to the tachycardia circuit is
      obtained by an analysis of the relationship between the postpacing interval and
      the tachycardia cycle length. Advances in mapping from multiple simultaneous
      sites, along with the ability to create larger, deeper lesions will be needed in
      order to cure a larger number of these patients. Ultimately, in some cases one
      must consider each procedure palliative rather than curative, as the disease
      progresses and substrate evolves and more tachycardia circuits become active.

PMID- 9272521
TI  - Can intraatrial reentry be prevented by changes in surgical technique?
AB  - Intraatrial reentry tachycardias can be prevented by surgical technique. Crucial
      in prevention is not to create areas of slow conduction. Also, the integrity of
      the terminal crest appears to be essential for normal impulse propagation; at
      surgery the crest should preferably be left intact. The number of incisions in
      the atrium should be kept to an absolute minimum. One single incision is the
      best. Therefore, it is also better to cannulate the caval veins directly instead
      of using the right atrial auricle.

PMID- 9272520
TI  - Radiofrequency ablation of intraatrial reentrant tachycardia after surgery for
      congenital heart disease.
AB  - Intraatrial reentry tachycardia is a common cause of both morbidity and mortality
      after surgery for a variety of congenital heart defects. Despite an armamentarium
      of arrhythmia management tools, including drug therapy, antibradycardia, and
      antitachycardia pacing, and catheter ablation, management of these arrhythmias
      remains a challenge. This report briefly reviews the problem, assesses the
      current successes and failures of radiofrequency catheter ablation for treating
      it, and discusses a number of ongoing developments that may improve both early
      and late outcome.

PMID- 9272522
TI  - Antitachycardia pacing.
AB  - Patients who have attempted repair of congenital heart disease often develop
      bradycardia and tachycardias postoperatively. The two dysrhythmias each make
      treatment of the other more difficult. Pacing is the only modality that addresses
      both brady- and tachycardias, without adversely influencing the other. Most
      postoperative tachycardias are reentrant, and thus uniquely susceptible to
      overdrive pacing. Usually an atrial single lead system is used. The patients most
      commonly encountered are those with extensive atrial surgery, such as atrial
      septal defect (ASD) repair. Mustard and Senning repair of d-transposition, and
      the various types of Fontan operations. The results are excellent for ASD repair
      and postoperative transposition, but only fair for postoperative Fontan patients.

PMID- 9272523
TI  - Sotalol for atrial tachycardias after surgery for congenital heart disease.
AB  - Atrial tachycardias, in particular atrial flutter after surgery for congenital
      heart disease, is associated with a high mortality. Treatment with various
      antiarrhythmic drugs and/or antitachycardia pacemakers is not very successful.
      Sotalol, a Class III drug, has shown to be a promising drug in adults with atrial
      tachycardias. However, the experience with sotalol in children after surgery for
      congenital heart disease is limited. Therefore, we describe our results here.
      Between December 1990 and February 1997, 26 children with atrial tachycardias,
      most of them with atrial flutter or fibrillation (n = 20), after surgery for
      congenital heart disease were treated with sotalol orally. The age of the
      children at the start of treatment was 7.5 +/- 5.8 years (mean +/- SD). The time
      interval between surgery and the start of atrial tachycardia ranged from 1 day to
      14.3 years (3.8 +/- 3.8 years). Conversion to sinus rhythm was achieved in 16 out
      of 22 hemodynamically stable children with a dosage of 4.0 +/- 1.6 mg/kg per day.
      The six children without sinus rhythm on sotalol and four hemodynamically
      unstable patients were treated prophylactically with sotalol after DC
      cardioversion for their tachycardias. Two children complained of mild transient
      fatigue. Heart rate decreased during therapy (95 +/- 33 vs 81 +/- 21 beats/min; P
      = 0.01). QTc-intervals did not change. Proarrhythmias such as torsades de pointes
      were not encountered. Two children with a preexistent sick sinus syndrome showed
      aggravation of bradycardia and needed pacemaker implantation. The percentage of
      children with a recurrence-free interval of 1 and 2 years was 96% and 81%,
      respectively, for all atrial tachycardias, and 92% and 66% for atrial flutter.
      The recurrences of atrial tachycardias during the follow-up period, which ranged
      from 0.1-6.1 years (2.5 +/- 1.8 years) could be treated with only an increase of
      the dosage of sotalol in all but one patient. We conclude that sotalol is an
      effective drug for the treatment and prevention of atrial tachycardia in children
      after surgery for congenital heart disease.

PMID- 9272525
TI  - Estimating defibrillator longevity: a need for an objective comparison.

PMID- 9272524
TI  - Amiodarone as treatment for atrial tachycardias after surgery.
AB  - Atrial flutter, including all types of postoperative atrial tachycardias, is the
      one with the highest risk of late sudden death. Thus, late postoperative atrial
      tachycardias must be suppressed and all patients should be permanently treated
      after a first episode of atrial flutter. Daily oral doses of 200-250 mg/m2
      amiodarone were found to be highly effective and well tolerated in young
      patients. However, in older patients and after long-term therapy, its use is
      restricted by adverse side-effects. In these cases, association of lower doses of
      antiarrhythmic agents, including amiodarone, may be effective and well tolerated.
      The use of other therapeutic options such as radiofrequency ablation should also
      be considered in older patients having drug-refractory postoperative atrial
      flutter.

PMID- 9272527
TI  - Right side implant of the unipolar single lead defibrillation system.
AB  - The active can defibrillator has been designed for implantation in the left
      prepectoral region. Whether this system can be successfully implanted on the
      right side is unknown. We describe six cases in which placement of the unipolar
      single lead defibrillation system was successfully attempted in the right
      prepectoral region due to impediments on the left side. The mean age of the
      patients was 62 +/- 12 years. Five patients had ischemic heart disease and one
      idiopathic dilated cardiomyopathy. The endocardial defibrillation electrode was
      placed in the right ventricle through the right subclavian vein and positioned at
      the apex in two patients and in the septal position in four patients.
      Defibrillation threshold testing was performed using a step-up/step-down protocol
      beginning at 12 J with 3-J increments or decrements. Defibrillation threshold was
      defined as the lowest energy of the first shock able to terminate ventricular
      fibrillation. The generator models used were the Medtronic 7218C in 1 patient,
      the Medtronic 7219C in 3 patients, and the Ventritex Cadet 115 AC in 2 patients.
      The mean defibrillation threshold was 15 +/- 3 J. The defibrillation thresholds
      were retested at 1, 3, and 6 months, and showed no significant change in five
      patients but decreased from 15 J to 12 J in one patient. The presence of
      impediments on the left side should not preclude attempts to place the unipolar
      active can system in the right prepectoral region.

PMID- 9272526
TI  - Risk factors for venous obstruction in children with transvenous pacing leads.
AB  - To determine the incidence and risk factors for venous obstruction in children
      with transvenous pacing leads, 63 children were evaluated clinically and
      echocardiographically. Patients with abnormal clinical and/or echocardiographic
      findings were further investigated by venography. Thirteen patients (21%) had
      evidence of venous obstruction. Venography in 11 (2 refused) showed that severity
      of obstruction (as defined by percentage of luminal narrowing) was complete
      (100%) in 3, severe (> 90%) in 4, and moderate (60%-90%) in 5 (1 patient having 2
      sites of obstruction). Risk factors for obstruction in 55 patients with single
      implantation procedures (10 with obstruction; 18%) were sought. Total cross
      sectional area of lead(s) was indexed to body surface area at implantation
      (INDEX). Patients with obstruction had a higher mean INDEX (7.6 +/- 1.6 mm2/m2)
      than patients without obstruction (4.9 +/- 2.0 mm2/m2); P < 0.0002). Receiver
      operator characteristic curves showed an INDEX > 6.6 mm2/m2 to best predict
      obstruction, with a sensitivity of 90% and specificity of 84%. Since pacing is
      lifelong, sizing of transvenous leads to the child is important to prevent
      obstruction and preserve venous access.

PMID- 9272528
TI  - Correlation of the heart rate-minute ventilation relationship with clinical data:
      relevance to rate-adaptive pacing.
AB  - The heart rate (HR)-minute ventilation (VE) relationship has been shown to be
      nonlinear and can be expressed as two distinct straight lines. This study is to
      assess the correlation of the initial HR-VE slope to clinical parameters. Maximum
      treadmill exercise tests were performed in 100 healthy volunteers (age 19-77
      years) using a ramp protocol in which work-rate increases linearly with exercise.
      Breath-by-breath VO2, VCO2, and VE were measured, and HR and BP were monitored
      throughout the exercise. The HR-VE curve demonstrated nonlinearity with a
      breakpoint determined by a change point analysis. This breakpoint was
      significantly higher than that of the anaerobic threshold. The VE at the HR-VE
      breakpoint was 56.4 +/- 19.4 and VE at the VE-VO2-VO2 breakpoints were 48.0 +/-
      18.3 (P < 0.0001) and 40.1 +/- 16.5 (P < 0.0001), respectively. The HR at this HR
      Ve breakpoint was 77.7 +/- 12.9% of the HR range. The first slope, S1 (1.76 +/-
      0.64) was steeper than the second slope, S2 (0.66 +/- 0.39). Although there was a
      gender difference for S1, the best clinical predictor on a stepwise multiple
      regression analysis was body surface area (BSA) which explained 47% of the
      variance. It was concluded that nonlinearity of the HR-VE curve can be expressed
      as two straight lines. The breakpoint is beyond the anaerobic threshold and can
      be estimated to be approximately 75% of the maximal predicted HR. BSA is the only
      clinical parameter that significantly predicts the initial slope of the HR-VE
      curve. This can be of great importance in the programming of rate-adaptive
      pacemakers using a VE.

PMID- 9272529
TI  - Safety of high energy internal cardioversion for atrial fibrillation.
AB  - High energy internal cardioversion has been proposed as an alternative method to
      cardiovert drug refractory or external cardioversion refractory atrial
      fibrillation. However, the safety of this technique has not been clearly
      evaluated. We reviewed findings in 53 patients who underwent 55 sessions of high
      energy internal cardioversion (2 patients underwent 2 sessions) for termination
      of longstanding atrial fibrillation. Shocks energy varied from 70-270 J. Three
      patients had 3 shocks during the same session, 5 had 2, and 47 only 1. Success
      rate was 89% (success was defined as immediate conversion to normal sinus
      rhythm). Low cardiac output occurred in two patients, and resulted in the death
      of one of these individuals, a patient with significant hypertrophic
      cardiomyopathy and heart failure. The other patient recovered completely. In 11%
      of the cases, shock induced transient atrioventricular block, necessitating
      ventricular pacing until sinus rhythm was restored. In three patients, a moderate
      but asymptomatic and uncomplicated pericardial effusion was diagnosed on
      echocardiogram. Finally, four patients had side effects related to venous
      puncture, which resolved spontaneously. These results suggest that high energy
      internal cardioversion is effective for conversion of atrial fibrillation.
      However, the technique may not be optimal in patients with advanced hypertrophic
      cardiomyopathy and in such cases the technique should be used carefully and only
      in the case of failure of external cardioversion; no more than two shocks should
      be delivered during the same procedure. Temporary ventricular pacing should be
      provided in all patients and an echocardiogram should be performed before
      patients are being discharged.

PMID- 9272530
TI  - Derivation of a defibrillator implant criterion based on probability of
      successful defibrillation.
AB  - Common criteria for implant of a cardioverter defibrillator include verification
      of a 2:1 energy safety margin or a fixed safety margin of 10 joules. These
      criteria have been established empirically. We present a statistically model
      based on defibrillation efficacy curves which may be used to establish a
      criterion which would meet a predetermined target. As an example, an implant
      criterion is derived based on a goal of 1-year sudden cardiac death survival of
      at least 99% by selecting an expected first-shock efficacy to meet that target.
      Logistic regression was performed on data from over 1,500 defibrillator implants
      including successful epicardial and transvenous electrode system implants as well
      as data from unsuccessful implants. A random sample from these curves was used to
      generate a representative sample of 1,000 potential implant candidates. By
      assuming successful defibrillation using a series of shocks at specified
      energies, i.e., choosing an implant criterion, the probability of successful
      defibrillation of the patient by a single shock at a predetermined maximum output
      can be established. Independent data are used to validate the model's accuracy in
      predicting defibrillation efficacy within the derived example.

PMID- 9272531
TI  - Characterization of the factors that determine the effect of sympathetic
      stimulation on heart rate variability.
AB  - Heart rate variability analysis has been used to derive indices of sympathetic
      tone. As different sympathetic stimuli may give rise to divergent changes in
      heart rate variability, this study was designed to characterize the factors
      responsible for these divergent responses. Twelve healthy subjects (7 males, age
      24.8 +/- 3.1 years) were evaluated. Five-minute electrocardiographic recordings
      were obtained at baseline, following upright tilt, and during isoproterenol
      infusion (25 ng/kg per min) under control conditions and following
      parasympathetic blockade. Data were acquired during spontaneous respiration and
      when breathing was timed with a metronome (15 breaths/min). Under control
      conditions, both upright tilt and isoproterenol infusion resulted in significant
      decreases in the SD and MSSD from baseline values of 69 +/- 3 ms and 64 +/- 5 ms
      to 48 +/- 4 ms and 21 +/- 5 ms during tilt and 44 +/- 4 ms and 20 +/- 5 ms during
      isoproterenol infusion, respectively. LF power also significantly increased from
      0.47 +/- 0.17 ln (beats/min)2 at baseline to 1.90 +/- 0.20. In (beats/min)2 and
      1.34 +/- 0.18. In (beats/min)2 during tilt and isoproterenol infusion,
      respectively. No change in HF power was noted. Following parasympathetic
      blockade, all heart rate variability parameters were significantly decreased. No
      significant change from baseline in the SD, MSSD, or HF power was noted with
      either tilt or isoproterenol infusion. The LF power increased only with tilt from
      a baseline value of -3.17 +/- 0.17 in (beats/min)2 to -0.41 +/- 0.19 in
      (beats/min)2. Similar changes were noted during spontaneous respiration and
      metronome breathing. These findings demonstrate that the response of the sinus
      node to beta-adrenergic stimulation depends on the mode of stimulation. In
      addition, the associated level of parasympathetic tone affects the observed
      changes in heart rate variability that are associated with sympathetic
      stimulation.

PMID- 9272532
TI  - Probability density function revisited: improved discrimination of VF using a
      cycle length corrected PDF.
AB  - The probability density function (PDF) describes the fraction of time an
      electrogram signal spends at the baseline. In normal rhythm the signal is at
      baseline during the period between electrogram complexes, while in fibrillation
      the signal exhibits continuous activity and spends little time at baseline.
      However, time spent at the baseline is dependent on the rate of the rhythm, which
      limits the ability of the PDF algorithm to discriminate ventricular fibrillation
      from fast nonfibrillatory rhythms. A cycle length corrected version of the PDF
      algorithm has been formulated, which only examines the electrical activity
      between detected beats. The algorithm was developed utilizing a training set of
      77 endocardial recordings and tested utilizing a test set of 90 endocardial and
      56 epicardial recordings. Ventricular fibrillation was detected with 100%
      sensitivity and 98% specificity.

PMID- 9272533
TI  - Local repolarization abnormalities induced by transcatheter radiofrequency
      ablation in pigs.
AB  - Radiofrequency (RF) ablation alters action potential repolarization of myocardial
      cells and, theoretically, this should induce ST-T segment changes in the ECG.
      Since these ECG abnormalities have been rarely reported in patients submitted to
      RF ablation we assess the ability of the procedure to cause ST-T segment changes
      in local electrograms. Epicardial ECG mapping was performed in 17 anesthetized
      open chest pigs submitted to endocardial (n = 9) or to epicardial (n = 8)
      unipolar radiofrequency ablation (500 kHz, 20 W for 5-10 s). To characterize the
      cellular electrophysiological alterations induced by RF ablation transmembrane
      action potentials were recorded at various distances from the ablation lesion;
      these were compared with seven control pigs. Endocardial RF ablation induced a
      transient (< 5 min) change of 6.1 +/- 2.4 mV in T wave amplitude (baseline: 12.8
      +/- 5.6 mV, P < 0.001) in 141 out of 269 epicardial electrodes. T wave changes
      were associated with shortening in local activation time (20.1 +/- 2.3 ms at
      baseline vs 18.5 +/- 2.5 ms at 60 s after ablation, P = 0.03). RF current caused
      persistent St segment elevation at the center of the ablation lesion with no
      transmural expansion. Intracellular potentials along a 2-6 mm wide myocardial
      band bordering the RF lesion lower amplitude (101 +/- 7.0 mV vs 71 +/- 23 mV, P <
      0.01) and shorter duration (254 +/- 44 ms vs 156 +/- 29 ms, P < 0.01) than
      control hearts. The center of the ablation lesion was electrically unexcitable.
      We concluded that RF ablation alters cellular electrophysiology in small areas
      surrounding the ablation lesion and this causes short-lasting transmural changes
      in T 3 wave amplitude and nontransmural ST segment elevation.

PMID- 9272534
TI  - Single pass lead VDD pacing in children and adolescents.
AB  - Implantation of permanent pacemakers in children and adolescents is possible but
      usually is limited to single chamber generators. The natural growth of these
      patients may require physiological pacing, but until recently two leads were
      required for this type of pacing. The single pass lead VDD pacing mode makes
      possible physiological pacing by using only one lead, for both atrial sensing and
      ventricular sensing and pacing. The feasibility of VDD pacing using endocardial
      lead was evaluated in 16 children and adolescents with congenital or postsurgical
      atrioventricular block. Their mean age was 7.9 +/- 4.9 years (range 1-16 years)
      and the smallest patient's weight was 8.2 kg. In all the patients, a single pass
      pacing lead with atrial sensing rings and bipolar ventricular pacing and sensing
      capability was implanted through the left or right subclavian vein. The pacemaker
      generator was implanted in a rectopectoral position. The mean atrial electrogram
      during the implantation was 4.2 +/- 2.1 mV and 2.6 +/- 1.9 mV after a mean of 1
      week. The ventricular pacing threshold was 0.5 +/- 0.2 V; the ventricular pacing
      impedance was 560 +/- 95 omega; and the ventricular electrogram amplitude was 9.9
      +/- 2.1 mV. This is a first report to demonstrate the feasibility of atrial
      synchronous ventricular endocardial pacing using a single pass lead in a
      relatively large group of children and adolescents.

PMID- 9272535
TI  - Use of single lead VDD pacing in children.
AB  - The development of transvenous ventricular pacing leads with proximal electrodes
      capable of atrial sensing and the recent availability of smaller generators has
      created the opportunity to treat children with complete AV block and normal sinus
      node function with a transvenous single lead VDD pacing system. Studies in adults
      have demonstrated this system to be efficacious with low complication rates.
      Transvenous single lead VDD pacemakers were implanted in ten children, aged 5-15
      years, between December 1993 and April 1996, in our institution. The indications
      were complete AV block with severe bradycardia in 5 patients, second-degree or
      complete AV block following congenital heart surgery in 3, complete AV block with
      long QT syndrome in 1, and second-degree AV block and syncope in 1. There were no
      complications related to the procedure in any case. P and R wave amplitudes were
      measured and thresholds were determined intraoperatively on all patients.
      Amplitudes and thresholds were remeasured on seven patients with a mean follow-up
      of 17 months; Holter monitors were performed on seven patients with mean follow
      up of 16 months. P and R wave amplitudes were generally diminished at follow-up
      compared to initial values but remained within an acceptable range for all
      patients. Four patients required reprogramming after pacemaker insertion, 1
      received an atrial lead for dual chamber pacing, 1 required reposition for lead
      dislodgment, and 1 patient required a new lead for an inadequate ventricular
      pacing threshold. No patient had evidence of failure to sense or capture as
      evaluated by Holter monitoring at last follow-up. Single lead VDD pacing systems
      can be successfully used in properly selected children with high degree or
      complete AV block with normal sinus node function.

PMID- 9272536
TI  - Single pass VDD pacing in children and adolescents.
AB  - Use of a single pass lead for VDD pacing in complete heart block is well
      described in adults, but there are only brief reports of its use in children. We
      have used standard adult size single pass leads in 13 children and adolescents
      aged 3.7-17.2 years (mean 10.1 years) and weighing 13.5-76 kg (mean 34.8 kg).
      Congenital complete heart block was present in 7 patients, surgical complete
      heart block in 5 patients and 2:1 AV block of unknown cause in 1 patient. In four
      patients, the VDD system was their first pacing system. In nine of the patients,
      1-6 previous systems had been used and simultaneous extraction of ventricular
      leads and/or atrial leads was performed. Leads of four different types were used:
      Brilliant IMP15Q, Brilliant + IMR15Q, CapSure 5032, and Unipass 425-13 with 4
      different generators: Saphir 600, Saphir II 620, Thera VDD 8948, and Unity 292
      07. At implantation, via a subclavian vein puncture, excess lead was advanced
      into the right atrium to allow both atrial sensing and slack for further growth.
      Ventricular thresholds ranged from 0.2-0.7 V. The minimal atrial amplitude was
      0.7-4 mV and the maximum amplitude was 2.5-8 mV. There were no complications. All
      patients have maintained adequate atrial signals for reliable pacing with follow
      up of 3-36 months (mean 17.6 months) during which time some have undergone
      considerable growth. Reliable atrial synchronous ventricular pacing is possible
      in growing children with complete heart block using a standard adult single pass
      lead.

PMID- 9272537
TI  - Comparative left ventricular function following atrial, septal, and apical single
      chamber heart pacing in the young.
AB  - Ventricular pacing, typically initiated from a RV apical electrode, inherently
      causes abnormal biventricular activation, decrease LV function, and causes
      histopathological changes. Since pacing initiated in childhood can be expected to
      have a more protracted course compared with the adult, the consequences of this
      alteration in LV hemodynamics gain added significance among the young pacemaker
      recipient. The purpose of this study was to evaluate the potential of improving
      paced LV function by a septal electrode implant site. Acute alterations in
      cardiac index, LV pressure, and contraction indices, including dP/dt, Vmax, and
      Vpm, were compared among 22 patients (median age 10 years) with normal cardiac
      anatomy during intracardiac electrophysiological studies. LV hemodynamics were
      measured during intrinsic rhythms and following 15 minutes of atrial, RV apical,
      and septal pacing at an appropriate exercise rate for age of 150 ppm. Results
      showed a significant decrease in LV dP/dt, Vmax, and Vpm, and increase in LV end
      diastolic pressure only with apical pacing. Septal pacing, in spite of loss of
      any atrial contribution to ventricular filling, maintained comparable indices
      with intrinsic and atrial paced rhythms. This study demonstrates that normalized
      LV function is maintained by septal and deteriorates with apical pacing acutely
      among young, nonischemic hearts. Continued evaluation of appropriate pacing
      electrode designs to permit septal implant is needed to ensure optimal
      chronically paced LV function.

PMID- 9272538
TI  - Atrial fibrillation: maintaining stability of sinus rhythm or ventricular rate
      control? The need for prospective data: the PIAF trial.
AB  - Atrial fibrillation is one of the most commonly encountered clinical arrhythmias.
      Different treatment options for this rhythm disorder exist with the electrical
      and/or pharmacological cardioversion to sinus rhythm with subsequent
      antiarrhythmic drug therapy to prevent recurrences being one of the primary
      therapeutic goals. Another alternative, however, is represented by the control of
      the ventricular rate in patients with persistent atrial fibrillation. The
      question of which these two strategies should be preferred in the majority of
      patients with atrial fibrillation has not been studied in a prospective way.
      Given the background of conflicting data with respect to the prognostic impact of
      atrial fibrillation and of the increasing evidence concerning the risks of
      antiarrhythmic drug treatment in atrial fibrillation, a prospective multicenter
      trial has been initiated to compare these two therapeutic alternatives
      prospectively. Patients will be randomly assigned to cardioversion with
      subsequent antiarrhythmic drug therapy to prevent recurrent atrial fibrillation
      or to a therapy aiming exclusively at control of the ventricular rate during
      persistent atrial fibrillation. All patients will receive anticoagulation by
      means of warfarin (target INR 2.5-3.5) to prevent thromboembolic complications.
      The rationale and the design of the PIAF trial (Pharmacological intervention in
      Atrial Fibrillation) are discussed below. The pilot phase of this study has begun
      patient enrollment in the spring of 1995.

PMID- 9272539
TI  - The paradox in using electrically stimulated skeletal muscle to pump blood.
AB  - For over four decades, various methods have been described for the use of
      electrically stimulated skeletal muscle to pump blood. To date, there has been no
      way of predicting the efficacy or long-term pumping capabilities of these
      methods. This article reviews the basic physiological properties of skeletal
      muscle and relates them to the blood pumping task and illustrates the paradox,
      namely a high preload is needed for a forceful contraction, but a high prolonged
      preload produces muscle ischemia and early fatigue. However, the high preload is
      only required just before muscle contraction. Two methods are described to attain
      the high preload and high muscle capillary blood flow.

PMID- 9272541
TI  - Can electrophysiologists survive the new era of health care reform?

PMID- 9272540
TI  - Atrial premature beats preceding episodes of paroxysmal atrial fibrillation:
      factorial analysis of a prediction system.

PMID- 9272542
TI  - Adenosine-induced right bundle branch block in a patient with recurrent
      tachycardia.

PMID- 9272543
TI  - Longitudinal dissociation in the his bundle: a possible mechanism of two distinct
      cycle lengths in atrioventricular reentrant tachycardia.
AB  - Two wide QRS tachycardias with identical morphology but different cycle lengths
      (CLs) developed in a 63-year-old man. Electrophysiological study demonstrated
      inducible atrioventricular reentrant tachycardia (AVRT) due to a concealed left
      posterior accessory pathway (AP), which was successfully ablated by
      radiofrequency application. Neither dual AV nodal pathways nor other APs were
      documented. Splitting of the His-bundle electrogram was shown, and programmed
      stimulation induced sudden prolongation of intra-hisian conduction time. These
      results suggest longitudinal dissociation in the His bundle may be responsible
      for two distinct CLs in AVRT without dual AV nodal physiology.

PMID- 9272544
TI  - Responses of normal subjects during 80 degrees head upright tilt table testing
      with and without low dose isoproterenol infusion.
AB  - Head upright tilt table testing has emerged as a standard technique for the
      evaluation of patients with recurrent unexplained syncope. To determine the
      specificity of head upright tilt table testing with and without a low dose
      isoproterenol infusion, the following study was undertaken. A total of 34 normal
      volunteers (21 men, 13 women, mean age 32.9 +/- 1.7 years) with no history of
      syncope, presyncope, or vertigo underwent head upright tilt table testing for 45
      minutes. A positive test was defined as the production of syncope or presyncope
      associated with hypotension and bradycardia. If the test was negative the patient
      was lowered to the supine position and a low dose isoproterenol infusion started
      (sufficient to raise the heart rate 20-25% above baseline) and the patient
      retilted for 20 minutes. Three subjects (8.8%; 95% CI: 2, 26; P = 0.23) developed
      syncope during the test, two during the baseline tilt, and one during
      isoproterenol infusion. Interestingly, one of these subjects later had a clinical
      syncopal episode. We conclude that head up tilt table testing at 80 degrees with
      or with out low level isoproterenol infusion provides an adequate specificity.

PMID- 9272545
TI  - Quinine may trigger torsades de pointes during astemizole therapy.
AB  - Because of serious cardiovascular events, warnings against concomitant use of
      certain medications with the use of antihistamine (HismanalR have been published
      and added to product labeling. Quinine, the optical isomer to quinidine, is
      included in these warnings. We present the case of a patient with only mild
      electrolyte disturbances who experienced an episode of torsades de pointes after
      a single dose of quinine while taking astemizole.

PMID- 9272546
TI  - Malfunction of an active fixation J-shaped screw-in atrial electrode lead: a case
      report.
AB  - Active fixation leads, using active grasping devices, ensure good postoperative
      lead fixation, long-term performance, and make possible later lead removal on
      demand. However, these delicate designs have not been without practical
      difficulties. We present two cases of fixation stylet fracture during helix
      extension and retraction maneuver respectively with resultant lead inoperability
      and abandonment. The fixed leads could be removed by torquing the entire lead
      counterclockwise.

PMID- 9272547
TI  - Should unipolar pacemaker leads be banned? Lessons from pacemaker/implantable
      cardioverter defibrillator interactions.

PMID- 9272548
TI  - The potential for seatbelt trauma to cause pacemaker pocket injury and subsequent
      erosion.

PMID- 9272550
TI  - Host cells of Toxoplasma gondii encystation in infected primary culture from
      mouse brain.
AB  - In order to identify brain cell types that serve as host cells of Toxoplasma
      gondii encystation primary cultures from murine brain were infected and stained
      for neural and parasite stage-specific markers. In mixed culture inoculated with
      T. gondii tachyzoites, MAP2+ neurons, GFAP+ astrocytes, F4/80+ microglia, and O1+
      oligodendrocytes proved to be infected as detected by parallel labeling of SAG1.
      At 4 days following infection with bradyzoites, cysts developed in neuronal,
      astroglial, and microglial host cells as clarified using bradyzoite-specific
      antibody 4F8. Additional staining of SAG1 revealed that astrocytes in bradyzoite
      infected brain cell culture can also harbor tachyzoite-containing vacuoles. Stage
      conversion was observed shortly after inoculation and was accompanied by an
      increase in] parasite proliferation. However, tachyzoites became rare in
      prolonged culture. By contrast, the numbers of cysts and of the bradyzoites
      isolated multiplied during long-term culture. These findings demonstrate that
      both glial and neuronal host cells allow T. gondii encystation in the absence of
      T cell-derived cytokines and imply that a brain-internal spreading of bradyzoites
      may sustain chronic infection.

PMID- 9272549
TI  - Pacing leads appear to be simple, mechanical structures, but they have not
      improved in reliability in a parallel fashion to pulse generators.

PMID- 9272551
TI  - Effects of diet on the lipid composition of Echinostoma caproni (Trematoda) in
      ICR mice.
AB  - High-performance thin-layer chromatography (HPTLC) was used to determine neutral
      lipids and phospholipids in the intestinal trematode Echinostoma caproni from
      experimentally infected ICR mice fed a high-fat diet (hen's egg yolk) as compared
      with worms from mice fed a standard laboratory diet. Worms were removed from the
      hosts at 2, 3, and 4 weeks postinfection (p.i.). Analysis by TLC-densitometry
      showed significantly greater amounts of triacylglycerols and free sterols at 2,
      3, and 4 weeks p.i. in worms from mice on the high-fat diet as compared with
      worms from mice on the standard laboratory diet. Significantly greater amounts of
      phosphatidylcholine and phosphatidylethanolamine were found in worms from mice on
      the high-fat diet as compared with worms from those on the standard diet at 2
      weeks p.i. but not at 3 and 4 weeks p.i. The results of this study suggest that
      the host diet influences the lipid content of E. caproni adults.

PMID- 9272552
TI  - Use of random amplified polymorphic DNA-polymerase chain reaction for the
      definition of genetic markers for species and strains of porcine Oesophagostomum.
AB  - Nodular worms are common parasites of pigs, and research has recently started to
      focus on the biology of these nematodes. However, the methods for delineation of
      species at immature developmental stages and for differentiation of various lines
      of the same species remain limited. For differentiation of porcine
      Oesophagostomum species and strains by genomic fingerprinting, random amplified
      polymorphic DNA-polymerase chain reaction was performed on DNA derived from 20
      larval batches of anthelmintic-susceptible and resistant strains and isolates of
      these nematodes and 2 ruminant Oesophagostomum spp. Polymorphic DNA markers could
      be amplified with 9 of the 33 primers tested. In all, 13 markers were species
      specific and 6 markers could differentiate between strains or groups of strains.
      With a combination of the latter, artificially selected anthelmintic-resistant
      strains and the susceptible mother strain of O. dentatum could be delineated.
      When single adult worms were compared, considerable variations between strains of
      the same species and between individuals from the same strain could be detected.
      The differentiation of Oesophagostomum strains and species at all parasitic
      stages on the basis of genetic markers could greatly facilitate studies on the
      biology of these parasites.

PMID- 9272553
TI  - Strongyloides stercoralis: identification of antigens in natural human infections
      from endemic areas of the United States.
AB  - Using Western-blot analysis, we identified eight immunodominant antigens
      (apparent molecular weights 96, 86, 75, 56, 41, 32, 28, and 26 kDa) of
      Strongyloides stercoralis in natural human infections. For this study, 78
      individual serum samples were obtained from S. stercoralis-infected patients
      residing in endemic areas of the United States. Poly A+ RNA was translated in
      vitro in the rabbit-reticulocyte lysate system. The newly synthesized translation
      products were immuno-precipitated with S. stercoralis human infection sera. All
      eight of the identified antigens were detected in the immunoprecipitates. The
      potential of these antigens as targets for immunodiagnosis is also discussed.

PMID- 9272554
TI  - Cyst formation by Toxoplasma gondii in vivo and in brain-cell culture: a
      comparative morphology and immunocytochemistry study.
AB  - Formation of Toxoplasma gondii cysts was examined in cultured murine brain cells
      and was compared with the development of cysts in mouse-brain tissue. Cultures of
      mixed glial cells from neonatal mouse brain were infected with bradyzoites of the
      avirulent T. gondii strain DX. The development and maturation of Toxoplasma cysts
      was monitored for up to 63 days after inoculation. Transmission electron
      microscopy indicated that in-vitro-derived cysts were morphologically similar to
      tissue cysts and were located intracellularly, even for up to 63 days
      postinfection. For immunohistological and immunocytochemical examination of both
      in-vivo- and in-vitro-infected material, monoclonal antibody (mAb) CC2 was used.
      MAb CC2 was shown to detect specifically the underlying granular material of the
      cyst wall without binding to the limiting membrane of the parasitophorous
      vacuole. This reactivity of mAb CC2 allows the distinction of bradyzoite
      containing cysts from parasitophorous vacuoles harboring tachyzoites both in
      vitro and in vivo.

PMID- 9272555
TI  - Experimental infection of Rana pipiens tadpoles with Echinostoma trivolvis
      cercariae.
AB  - Studies were done on laboratory-raised Rana pipiens tadpoles experimentally
      infected with Echinostoma trivolvis cercariae. Tadpoles exposed individually to
      250 cercariae died within 24 h. They were edematous at death and their kidneys
      were heavily infected with metacercarial cysts. Of 20 tadpoles exposed to 100
      cercariae each, 9 survived the infection, and their growth was compared for 4
      weeks postinfection (p.i.) with that of 20 control tadpoles that had not been
      exposed to cercariae. There was a significant weekly decline in the total length
      and body weight of the infected versus control tadpoles. Surviving tadpoles
      retained their metacercarial infections in the kidneys following metamorphosis to
      frogs. Following exposure of tadpoles to cercariae, cercarial bodies were first
      seen in the kidneys by 0.5 h p.i. Metacercariae that were molding their inner and
      outer cyst walls were first seen at 2.3 h, and by 8.5 h the inner and outer cyst
      walls were clearly defined. Domestic chicks exposed to cysts aged 2.5 and 4.0 h
      did not become infected, whereas ovigerous adults of E. trivolvis were recovered
      from chicks fed 12-h-old cysts. Cercariae aged 6 to 8 h were more infective to
      tadpoles than were either 1- or 20-h-old cercariae. The E. trivolvis-R pipiens
      tadpole model is suitable for the study of host-parasite relationships of
      echinostome larvae in a cold-blooded vertebrate host.

PMID- 9272556
TI  - Evidence for the existence of genetically distinct strains of Enterocytozoon
      bieneusi.
AB  - Enterocytozoon bieneusi is the most frequently found microsporidium in human
      infections. In all, 3 distinct genotypes were detected in 12 stool samples from 8
      patients with acquired immunodeficiency syndrome (AIDS). A total of 9 polymorphic
      sites were found in the 243-bp-long internal transcribed spacer (ITS) of the rDNA
      gene, whereas none was found in 241 bp of adjacent rRNA coding regions. The
      genotype was stable in samples taken during 11 weeks of infection from one of the
      patients. The existence of and the ability to discriminate among strains of E.
      bieneusi are important prerequisites for elucidation of the hitherto unknown
      reservoirs of this pathogen and the mode of its transmission and may explain its
      pathogenicity.

PMID- 9272557
TI  - In vitro inhibition of liver forms of the rodent malaria parasite Plasmodium
      berghei by naphthylisoquinoline alkaloids--structure-activity relationships of
      dioncophyllines A and C and ancistrocladine.
AB  - Naphthylisoquinoline alkaloids are derived from Dioncophyllaceae and
      Ancistrocladaceae species and comprise a new class of promising antimalarials
      with a demonstrated potential against asexual erythrocytic Plasmodium falciparum
      and P. berghei stages in vitro. We report herein the pronounced activity of pure
      naphthylisoquinoline alkaloids against exoerythrocytic malaria parasites. P.
      berghei-infected human hepatoma cells (Hep G2) were incubated with culture medium
      containing selected alkaloids at 10 micrograms/ml. The most active compounds,
      showing inhibitory activity of more than 40%, were dioncophylline A (compound 1),
      dioncophyllacine A (compound 6), and ancistrobarterine A (compound 12). For
      structure-activity investigations of dioncophyllines A (compound 1) and C
      (compound 3) and ancistrocladine (compound 7) a selection of their analogs from
      natural or synthetic sources was examined. Dioncophylline A (compound 16), 5'-O
      demethyl-8-O-methyl-7-epi-dioncophylline A (compound 17), N-formyl-8-O-methyl
      dioncophylline C (compound 21), and N-formyl-8-O-benzoyldioncophylline C
      (compound 24) were found to display high levels of activity as well, although the
      former two compounds caused damage to the host-cell monolayers. As
      naphthylisoquinoline alkaloids are also highly active against blood forms of
      Plasmodium spp., they should be regarded as lead compounds for further
      development as drugs against erythrocytic and exoerythrocytic stages of
      Plasmodium spp.

PMID- 9272558
TI  - Humoral and cellular immune responses to experimental Fasciola hepatica
      infections in goats.
AB  - Humoral and cellular immune responses to Fasciola hepatica excretory-secretory
      products (ESPs) in primary and secondary experimental infections in goats were
      studied. Primary infection induced the development of chronic subclinical
      fascioliasis that did not affect the establishment of flukes coming from the
      secondary infection, as the same percentages of recovered flukes were found in
      both groups. The specific IgG response to F. hepatica ESPs was similar in primary
      and secondary infections; challenge flukes did not induce any modification in the
      IgG response. The specific lymphocyte response to F. hepatica ESPs was absent in
      most of the infected goats, both primarily and secondarily infected. A modulation
      of the nonspecific cellular responses to mitogens was also observed. All infected
      goats showed a reduced proliferative response to concanavalin A and
      phytohemagglutinin. According to our results, humoral and cellular responses to
      F. hepatica ESPs in goats have no protective effect on the establishment of
      flukes and the development of disease in either primary or secondary infections.

PMID- 9272559
TI  - Enzymatic basis for the lack of oxamniquine activity in Schistosoma haematobium
      infections.
AB  - The notion that oxamniquine is active against Schistosoma mansoni but inactive
      against S. haematobium was confirmed using in vitro cultures of adult worms.
      Since oxamniquine and hycanthone have been shown to become effective upon
      activation by a schistosome enzyme, enzymatic tests were carried out to detect
      possible differences between the enzyme of S. mansoni and that of S. haematobium.
      It was found that the S. mansoni enzyme could activate hycanthone and, to a
      lesser extent, oxamniquine. The S. haematobium enzyme, on the other hand, was
      capable of activating hycanthone but virtually incapable of activating
      oxamniquine. It is concluded that the different activity of oxamniquine in the
      two species is due to differences in the drug-activating enzyme.

PMID- 9272560
TI  - Immune response and protection in mice inoculated with Leishmania amazonensis
      clones expressing different degrees of virulence.
AB  - The induction of protective immunity to Leishmania amazonensis was investigated
      by injection of parasite clones of low and medium virulence into susceptible
      mice. To this end, L. amazonensis were cloned by limiting dilution and the
      clones' virulence was evaluated by the course of infection in susceptible mice.
      Clones originally derived from the spleen showed virulence variations in
      comparison with that of the parental population (PP) of parasites. Two low
      virulence clones (SP 5 and SP 20) and one medium-virulence clone (SP 11),
      representative of the spectrum of derived clones, were compared with virulent
      parasites and with an avirulent strain (Josefa) as to their ability to induce T
      cell immune responses and to protect BALB/c mice from infection with the virulent
      L. amazonensis PP. Clone SP 20 and clone SP 11 induced partial protection when
      injected by the intravenous and intradermal route, respectively. The avirulent
      Josefa strain induced neither T-cell responses nor protection. Low-virulence L.
      amazonensis clones can therefore be additional tools in vaccine investigation.

PMID- 9272561
TI  - Surface charge and surface carbohydrates of Cyptobia salmositica virulent and
      avirulent forms and of C. bullocki (Kinetoplastida: Cryptobiidae).
AB  - The surface charge and surface carbohydrate residues of the virulent (freshly
      isolated from the fish blood) and avirulent forms (from culture) of Cryptobia
      salmositica and one strain of C. bullocki were studied. Measurements of the zeta
      potential of parasites showed that C. bullocki and the virulent form of C.
      salmositica had a net negative surface charge of about -15 mV, whereas the
      attenuated form of C. salmositica showed a surface charge of -7.9 mV. Enzymatic
      treatments of parasites with neuraminidase, trypsin, or phospholipase C indicated
      the presence of sialic acid residues, phosphate groups, and protein
      glycoconjugates as components of the Cryptobia surface that accounted for their
      surface charge. Residues of alpha-D-man, alpha- and beta-D-gal, alpha-D-galNAc,
      alpha-L-fuc, and D-glcNAc could be detected on the surface of all parasites by
      specific fluorescein isothiocyanate (FITC)- and colloidal gold-labeled lectins.
      The cell surface of the avirulent form of C. salmositica showed the strongest
      reactivity to almost all lectins tested. A remarkable binding pattern of lectins
      in the anterior region of parasites was observed.

PMID- 9272562
TI  - Experimental infection of nude mice as a model for Sarcocystis neurona-associated
      encephalitis.
AB  - The development of a rodent model for the study of Sarcocystis neurona
      encephalitis is described. Animal models have been developed for a number of
      protozoal parasites; however, no such model exists for S. neurona. The approach
      used in this study is similar to that employed for other closely related
      protozoal parasites such as Neospora caninum and Toxoplasma gondii. A time course
      of infection was examined, and histopathology, immunohistochemistry, and parasite
      isolation were used to examine the pathogenesis and follow the infection from 1
      to 6 weeks postinoculation. S. neurona was associated with the development of
      encephalitis in these mice, and the immune status determined the susceptibility
      of these mice to S. neurona-associated encephalitis.

PMID- 9272563
TI  - Comparative reproduction of Cryptosporidium baileyi in embryonated eggs and in
      chickens.
AB  - At 2 days of age, each of 20 chickens was perorally or intracloacally infected
      with 3 x 10(5) oocysts of Cryptosporidium baileyi and maintained for 13 days post
      infection. In parallel, 20 embryonated chicken eggs were inoculated with 3 x
      10(5) oocysts at day 10 of embryonation and were incubated for a further 7 days.
      The average reproduction rates in the two groups of chickens were x560 after
      peroral infection and x533 after intracloacal infection as compared with x256 in
      the eggs. Although the rate of reproduction of parasites seen in the eggs was
      only about 50% of that observed in chickens, large numbers of oocysts could be
      harvested (on average, 77 million per egg versus 161 and 168 million from
      chickens). Nearly the same number of oocysts could be obtained from two eggs as
      compared with one chicken. The use of embryonated eggs accommodates the sense of
      animal-protection regulations, is less expensive, and allows the isolation of
      oocysts under sterile conditions.

PMID- 9272564
TI  - First isolation and characterization in humans of Entamoeba histolytica
      (laboratory-made) zymodeme XX.
AB  - Isoenzyme analysis by starch-gel electrophoresis has proved to be a useful method
      for the biochemical differentiation of pathogenic Entamoeba histolytica and non
      pathogenic E. dispar isolates. Of the known 24 zymodemes, 3 are laboratory-made
      and have not previously been identified in humans. Parasitology screening was
      carried out in a psychiatric institution. Two amebic stocks were isolated and
      characterized that had never previously been found in humans and that have
      protein patterns identical to that of the laboratory-made zymodeme XX.

PMID- 9272565
TI  - A new method for isolation and differentiation of native Entamoeba histolytica
      and E. dispar cysts from fecal samples.
AB  - A new method for the purification of protozoan cysts from feces was established,
      allowing to isolation of native cysts. The procedure consists of two sucrose
      density gradients and enzymatic digestion of cellulose particles by cellulase and
      can be accomplished in a few hours. The cyst fractions were differentiated into
      Entamoeba histolytica and E. dispar using the DNA probes P145 and B133 and a dot
      blot test.

PMID- 9272566
TI  - Therapeutic and prophylactic efficacy of the Ivomec SR Bolus against nematodes
      and Psoroptes ovis in cattle weighing more than 300 kg at the time of treatment.
AB  - Three trials using 50 European breed cattle were conducted to evaluate the
      therapeutic and prophylactic efficacy of the Ivomec SR Bolus against nematodes (2
      trials) and Psoroptes ovis (1 trial) in cattle weighing more than 300 kg at the
      time of treatment. The Ivomec SR Bolus proved to be highly effective against
      economically important gastrointestinal and pulmonary nematodes (Ostertagia
      ostertagi, Trichostrongylus axei, Cooperia punctata, Oesophagostomum radiatum,
      Dictyocaulus viviparus) and improved the rate of weight gain significantly. P.
      ovis was eliminated from cattle treated with an Ivomec SR Bolus. The treatment
      also provided prophylaxis against an infestation of P. ovis and increased the
      weight gain of cattle infested with P. ovis.

PMID- 9272567
TI  - Reduced egg counts in mixed infections with Oestrus ovis and Haemonchus
      contortus: influence of eosinophils?
AB  - In all, 2 groups of lambs were infected either with Oestrus ovis first-instar
      larvae or with 10,000 third-stage larvae (L3) of Haemonchus contortus. Another
      group of lambs was infected with both parasites. Fecal nematode egg counts,
      plasma pepsinogen concentrations, specific O. ovis enzyme-linked immunosorbent
      assay (ELISA) antibodies, and blood eosinophil counts were monitored and compared
      to with the values recorded for a control group of uninfected lambs. There was no
      significant difference between the burden of H. contortus found in mixed and
      single infections. However, the nematode egg production was significantly
      depressed in mixed infections. O. ovis affects the population of H. contortus at
      least by decreasing the parasite egg output. This effect may be mediated through
      the increase in eosinophil production stimulated by the presence of O. ovis.

PMID- 9272568
TI  - Observations on the surface coat of Blastocystis hominis.
AB  - The surface coat of Blastocystis hominis was studied in the electron microscope.
      In some cells the surface coat was seen in two layers; the external layer was
      more electron-dense and fragmented than the internal layer. It appears that the
      surface coat is being continuously formed by the parasite and shed in the
      environment. The fibrillar material of the surface coat attaches to the bacteria,
      in some cases, completely surrounding them, possibly causing cytoplasmic damage
      to the bacterial cell as indicated by loss of electron density.

PMID- 9272569
TI  - Long-term cultivation of Plasmodium falciparum in media with commercial non-serum
      supplements.
AB  - Continuous cultivation of both drug-sensitive and drug-resistant strains of
      Plasmodium falciparum was achieved using a mixture of commercially available
      serum substitutes. This provides easier standardisation of experimental data and
      minimises the risk of infection from handling of human serum. In addition,
      Nutridoma SR and AlbuMAXI are readily available and are biologically defined.
      Parasites grown in serum-free medium are morphologically and metabolically
      identical to those cultivated in medium supplemented with 10% human serum.

PMID- 9272570
TI  - Ultrastructural effects of nicarbazin in Eimeria tenella in chicks.

PMID- 9272571
TI  - Electron-microscopy observations on an intracellular mastigophoran in the gills
      of crucian carp, Carassius carassius.

PMID- 9272572
TI  - Characterisation of alpha 1A Ba2+, Sr2+ and Ca2+ currents recorded with the
      ancillary beta 1-4 subunits.
AB  - Xenopus oocytes have been injected with different combinations of expression
      plasmids carrying the rat brain alpha 1A and different beta (beta 1-4) Ca2+
      channel subunit cDNAs. Whole-cell Ba2+ and Ca2+ currents were recorded up to
      seven days after injection. Intra-oocyte injection of BAPTA allowed us to record
      uncontaminated Ba2+, Sr2+ currents. The alpha 1A calcium channel showed relative
      current amplitudes according to the sequence: IBa2+ > ISr2+ > ICa2+. The ratio
      ICa2+/IBa2+ was significantly larger when compared to the class C L-type Ca2+
      channel (alpha 1C). However, currents flowing through alpha 1A and alpha (1C)
      subunits saturate for similar Ba2+ concentrations and display the anomalous mole
      fraction effect in the presence of mixtures of Ba2+ and Ca2+ ions in the external
      medium. In oocytes expressing the alpha 1A Ca2+ channel subunit, switching from
      extracellular Ba2+ to Ca2+ also induced a depolarising shift of current-to
      voltage relation and the steady-state inactivation curve, and increased the time
      to-peak of the current. Inactivation kinetics were poorly affected. Changes in
      gating and voltage-dependence of activation, but not in the voltage-dependent
      inactivation, were independent from the coexpressed beta subunit (except with the
      beta 4 subunit). Our data constitute strong evidence for the existence of
      differences in intra-pore Ca2+ binding sites between the alpha 1C and alpha 1A
      subunits, and emphasise the influence of the charge carrier on the modulation of
      alpha 1A properties by the beta subunits.

PMID- 9272573
TI  - Functional differences of a Kv2.1 channel and a Kv2.1/Kv1.2S4-chimera are
      confined to a concerted voltage shift of various gating parameters.
AB  - When expressed in Xenopus oocytes, the voltage-dependent K+ channels Kv1.2 and
      Kv2.1 have similar steady state parameters of activation but the kinetics of
      activation is significantly faster in the Kv1.2 channels. Activation results from
      intramolecular arrangements which start with the movement of the voltage sensor
      and end with the opening of the pore. The S4-segment and the H5-loop comprise at
      least part of the respective involved structural elements. The molecular
      mechanism of coupling between sensing of voltage and opening of the pore is less
      well understood. We have measured whole cell and single channel ionic currents in
      the rapidly activating Kv1.2 channel of the rat, the slowly activating Kv2.1
      channel of the human, and in an S4-chimera Kv2.1/Kv1.2S4. With respect to the
      Kv2.1 channel, steady state activation and steady state C-type inactivation of
      the chimeric channel are shifted by more than 50 mV in the depolarizing
      direction. The property of rapid activation in Kv1.2 channels was not transferred
      to the Kv2.1 channels with the transplanted S4-region. Instead, the kinetics of
      activation, deactivation, and recovery from C-type inactivation as well as the
      voltage sensitivity of the 4-aminopyridine block are similar to the corresponding
      processes in Kv2.1 channels if they are related to the steady state activation
      and inactivation, respectively. The unitary current and the mean open time of
      single channel openings of the S4-chimeric channels resemble the respective
      values of Kv2.1 channels. It is concluded that the insertion of the S4-segment of
      Kv1.2 channels into Kv2.1 channels modifies the gating at the early steps of
      activation leaving all properties associated with the open state(s) of the Kv2.1
      channels unaffected.

PMID- 9272574
TI  - Ca(2+)-permeability of muscle nicotinic acetylcholine receptor is increased by
      expression of the epsilon subunit.
AB  - We have expressed muscle embryonic (alpha beta gamma delta) and adult (alpha beta
      delta epsilon) nicotinic acetylcholine receptors in Xenopus Laevis oocytes and
      measured their current reversal potentials in the presence of extracellular Na+,
      Ca2+, Sr2+ or Ba2+ ions. The ionic permeability ratio PCa2+/PNa+ was increased
      about 3 fold by the change in the subunit composition of the nicotinic
      acetylcholine receptor (replacement of the gamma by the epsilon subunit). A
      similar increase was also found when permeability to Ba2+ and Sr2+ ions was
      studies. Comparison of the nicotinic Ca2+ currents recorded from oocytes injected
      with embryonic or adult receptor subunit combinations also showed that the Ca2+
      influx was significantly increased by expressing the epsilon subunit. This
      increase was estimated to change the contribution of the Ca2+ current to the
      total net inward current from 0.8% (in the case of the alpha beta gamma delta
      receptor) to 2.5% (in the case of the alpha beta delta epsilon receptor). Taken
      together, these results suggest that important modifications in the acetylcholine
      mediated Ca2+ influx occurred during muscle innervation and underline the role of
      the nicotinic receptor in the developmental regulation of Ca2+ influx.

PMID- 9272575
TI  - Activation of a beta 2-adrenergic receptor/Gs alpha fusion protein elicits a
      desensitization-resistant cAMP signal capable of inhibiting proliferation of two
      cancer cell lines.
AB  - We showed in a previous study that the expression, in Gs-deficient S49 cyc-
      cells, of a fusion gene encoding the beta 2-adrenergic Receptor (beta 2AR) and
      the alpha subunit of the Gs protein (Gs alpha) restored beta 2AR-dependent
      activation of adenylyl cyclase. We report here the extensive characterization of
      short- and long-term regulation of the beta 2AR/Gs alpha fusion protein activity
      and its pharmacological effect after expression in two cancer cell lines. In
      contrast with native beta 2ARs and Gs, the receptor and the alpha s subunit
      moieties of the beta 2AR/Gs alpha fusion protein did not undergo functional
      uncoupling. After a sustained incubation with isoproterenol or forskolin, the
      accumulation of cAMP could still be observed in S49 beta Gs cells, expressing the
      fusion gene, which showed, in addition, an up-regulation of their beta 2AR
      binding sites, while in S49 wt cells, the same treatments completely abolished
      the rise of cAMP and markedly reduced the number of receptors. cAMP-activation of
      protein kinase A (PKA) is known to modulate proliferation of most cells. We
      studied the effect of long term beta 2AR/Gs alpha activation on the growth rate
      of S49 lymphoma cells and carcinoma carB cells, a highly proliferative cancer
      cell line expressing oncogenic ras protein. The beta 2AR agonist salmeterol
      blocked the proliferation of both S49 and carB beta 2Gs cells, while this
      treatment did not change the growth of wild-type cells. In carB beta 2Gs cells,
      this effect may be reinforced by a significant basal activity of the fusion
      protein and by agonist-promoted MAP kinase inhibition. In conclusion, the
      stimulatory overload provided by the beta 2AR/Gs alpha fusion protein led to the
      inhibition of cAMP-sensitive cancer cell proliferation in vitro.

PMID- 9272576
TI  - Inhibition of human immunodeficiency virus type 1 infection in a T-cell line
      (CEM) by new dipeptidyl-peptidase IV (CD26) inhibitors.
AB  - Phenylalanyl-pyrrolidine-2 nitrile (Phe-pyrr-2-CN) and arginyl(PMC)-pyrrolidine-2
      nitrile (Arg(PMC)-pyrr-2-CN) are two dipeptidyl peptidase IV/CD26 (DPP-IV/CD26)
      inhibitors designed and synthesized by our group. These two compounds suppress
      the enzymatic activity of DPP-IV/CD26 in a competitive and reversible manner.
      Pretreatment of CEM cells with either of the compounds yielded a marked albeit
      transient reduction of HIV infection, as measured by HIV1 p24 production, RT
      activity and syncytium formation. The ID50 value of the Phe-Pyrr-2-CN and
      Arg(PMC)-pyrr-2-CN in HIV1 inhibition was 5.3 microM and 2.4 microM,
      respectively. Administration of either of the DPP-IV/CD26 inhibitors 1 h after
      HIV1 infection did not suppress HIV1 production. An analog whose inhibitory
      activity toward DPP-IV/CD26 was abolished by blocking the N-terminal of Phe-pyrr
      2-CN with the 9-fluorenymethyloxycarbonyl (Fmoc) group had no effect on HIV1
      infection. An additive effect of HIV1 inhibition was observed in combinations of
      either of the DPP-IV/CD26 inhibitors with CD4 monoclonal antibody. These results
      suggest that DPP-IV/CD26 enzymatic activity may play a role in facilitating HIV1
      infection of human CD4+T cells at the entry process. DPP-IV/CD26 inhibitors may
      therefore have potential use in combination with other drugs to prevent HIV1
      transmission.

PMID- 9272577
TI  - HIV increases hepatitis C viraemia irrespective of the hepatitis C virus
      genotype.
AB  - In case of coinfection with hepatitis C virus (HCV) and human immunodeficiency
      virus (HIV), HCV viraemia is increased. Because the HCV genotype 1 is associated
      with elevated viraemia, the increase in HCV viraemia observed and described in
      HIV+ patients could be attributed to the predominance of HCV genotype 1 in these
      patients. Therefore, the purpose of this study was to quantify HCV RNA in
      patients coinfected with HIV and HCV, according to the HCV genotype. The HCV
      genotype was thus determined in serum samples of 59 HIV+HCV+ patients and 51 HIV
      HCV+ patients. HCV RNA was quantified using a branched DNA assay and the HCV
      genotype was determined using the "InnoLiPA" technique. The distribution of the
      HCV genotype was not significantly different in the two groups of patients, and
      there were even more patients infected by genotype 1 in the HIV-HCV+ group. The
      mean HCV viraemia of patients infected by HCV genotype 1 and by HCV genotype 3
      was higher in patients coinfected by HIV than in HIV- patients (p < 10(-7) and p
      = 0.05, respectively). The increase in HCV viraemia observed in HIV+ patients was
      not the result of a specific distribution of HCV genotype in these patients. HIV
      infection was responsible for an increase in HCV viraemia irrespective of the HCV
      genotype.

PMID- 9272578
TI  - The impact of dengue haemorrhagic fever on liver function.
AB  - The impact of dengue haemorrhagic fever (DHF) on liver function was studied by
      measuring serum transaminase levels on 45 patients with DHF confirmed by virus
      isolation and serodiagnosis in 1995. Abnormal levels of AST and ALT were observed
      in 97.7 and 37.3% of the patients, respectively. The fact that the level of AST
      was higher than that of ALT and that the elevation of transaminases was mild to
      moderate in most cases (< 5-fold greater than the normal upper limit for AST and
      ALT) showed that liver involvement was also mild to moderate in most cases of
      DHF. The results of transaminases did not differ significantly between cases with
      and without hepatitis B or hepatitis C virus infection, nor between primary and
      secondary cases of infection, but a significantly higher elevation of AST and ALT
      was observed in DHF patients with gastrointestinal haemorrhage. Two patients with
      dengue encephalopathy (in 1992) and one patient with dengue encephalopathy who
      died of massive gastrointestinal haemorrhage (in 1995) had unusually high
      transaminase levels as a sign of acute liver failure. It is concluded that DHF
      may cause mild to moderate liver dysfunction in most cases; only some patients
      may suffer from acute liver failure leading to encephalopathy and death.

PMID- 9272580
TI  - Identification of bovine rotaviruses in Venezuela: antigenic and molecular
      characterization of a bovine rotavirus strain.
AB  - Two serotypes of bovine group A rotaviruses were demonstrated by enzyme-linked
      immunoassay (ELISA) and polyacrylamide gel electrophoresis (PAGE) in 20 of 171
      faecal samples collected from diarrhoeic calves in two dairy farms in Venezuela.
      By serotyping ELISA using G and P serotype-specific monoclonal antibodies, bovine
      rotaviruses (BRV) circulating on one farm were identified as serotype G6, while
      BRVs circulating on the other farm were identified as serotype G10. Only one BRV
      (033) could be successfully isolated in MA104 cells, and the nucleotide sequences
      of the VP7 and the VP8* trypsin-cleavage product of the VP4 were determined.
      Cross-neutralization tests and comparative sequence analysis showed that BRV 033
      belonged to serotype G6 and genotype P1. This is the first report of BRVs
      identified in Venezuela.

PMID- 9272579
TI  - Seroepidemiological study of an acute hepatitis E outbreak in Morocco.
AB  - This study clearly shows that hepatitis E virus (HEV) was the major aetiological
      virus in an outbreak in the south of Morocco, in 1994. Acute hepatitis E was
      diagnosed using recombinant antigen-based enzyme immunoassays and reverse
      transcription polymerase chain reaction in 77.3% of patients. In the west of
      Morocco, 6.1% of controls were positive for anti-HEV IgG. The anti-HEV prevalence
      in patients was significantly higher than that of controls (84.0% vs. 6.1%) (P <
      0.001). In healthy contacts residing in southern Morocco, 10.4% had anti-HEV IgG,
      indicating past HEV infection. Furthermore, HEV-specific IgM was associated with
      subclinical HEV infection in 9 contacts and was noted in 10 others who were
      convalescent. Faecal contamination of drinking water samples collected from the
      epidemic city was observed. It also appeared that primary infection with HEV
      accounted for more than 86% of the cases. A longitudinal study showed waning of
      anti-HEV antibodies in patients and healthy contacts six months after the initial
      testing. Subclinical HEV infection was significantly prevalent in a paediatric
      population younger than 10 years (P < 0.05). Our results also showed that anti
      HEV IgG in healthy contacts decreased significantly after 30 years of age (P <
      0.01), whereas the clinical acute HEV infection incidence increased significantly
      with age (P < 0.01). From this study, it appears that HEV is present in both the
      west and the south of Morocco.

PMID- 9272581
TI  - Simple method for efficient production of hepatitis B virus core antigen in
      Escherichia coli.
AB  - To obtain good antigenicity and high purity of the hepatitis B virus core antigen
      (HBcAg) in large quantities without using the fused protein technique employed in
      recombinant DNA technology, a protein molecule with the same primary sequence as
      that of wild-type HBcAg (subtype adr) was directly expressed in Escherichia coli
      JM109 (DE3) using pGd1 expression vector. Purification of the expressed HBcAg
      yielded high-quality protein by means of simple purification steps, such as
      sonication, ammonium sulphate precipitation and heat treatment, before final
      purification by conventional ultra-centrifugation. The HBcAg preparation thus
      obtained contains small round particles similar in appearance to the HBcAg
      particles from the HBV-infected human liver tissue.

PMID- 9272583
TI  - Measles outbreak--Southwestern Utah, 1996.
AB  - During April 9-July 7, 1996, a total of 107 confirmed measles cases were reported
      from Washington County, Utah--one of five counties in the Utah Southwest Health
      District (USHD). Fourteen cases associated with this outbreak were reported from
      other counties in Utah and from Arizona, California, and Nevada. This report
      summarizes the epidemiologic investigation of the outbreak in Washington County
      (1995 population: 65,885) and demonstrates the potential for measles to spread in
      a school-aged population despite a high coverage rate for at least one dose of
      measles vaccine.

PMID- 9272582
TI  - Staphylococcus aureus with reduced susceptibility to vancomycin--United States,
      1997.
AB  - Staphylococcus aureus is one of the most common causes of both hospital- and
      community-acquired infections worldwide, and the antimicrobial agent vancomycin
      has been used to treat many S. aureus infections, particularly those caused by
      methicillin-resistant S. aureus (MRSA). In 1996, the first documented case of
      infection caused by a strain of S. aureus with intermediate levels of resistance
      to vancomycin (VISA; minimum inhibitory concentration [MIC]=8 microg/mL) was
      reported from Japan. This report describes the first isolation of VISA from a
      patient in the United States, which may be an early warning that S. aureus
      strains with full resistance to vancomycin will emerge.

PMID- 9272584
TI  - Human rabies--Montana and Washington, 1997.
AB  - On January 5 and January 18, 1997, respectively, a man in Montana and a man in
      Washington died of neurologic illnesses initially suspected to be Creutzfeldt
      Jakob disease (CJD) but diagnosed as rabies encephalitis during subsequent
      histologic examination on autopsy. The cases were not linked epidemiologically,
      and no secondary cases occurred. Postexposure prophylaxis (PEP) was administered
      to 113 potential contacts. This report summarizes the clinical presentations of
      the cases and the epidemiologic investigations by the Montana Department of
      Public Health and Human Services and the Washington State Department of Health;
      nucleic acid sequencing indicated that the silver-haired bat (Lasionycteris
      noctivagans) and the big brown bat (Eptesicus fuscus), respectively, were the
      probable sources of exposure.

PMID- 9272585
TI  - Behavioral Risk Factor Survey of Korean Americans--Alameda County, California,
      1994.
AB  - Asians/Pacific Islanders (APIs) account for an increasing proportion of all
      racial/ ethnic minority groups in the United States: during 1980-1990, the number
      of persons in this group increased approximately 99%. Among APIs in the United
      States, Korean Americans are the fifth largest subgroup. In Alameda County,
      California, APIs comprise 15% of the population, and Korean Americans account for
      5% of that group. To assess behavioral risk factors among Korean Americans in
      Alameda County, Asian Health Services (a nonprofit community clinic) and the
      Center for Family and Community Health at the University of California, Berkeley,
      conducted a household telephone survey from August 1994 through February 1995.
      This report summarizes findings from that survey, which indicate significant
      differences in the prevalences of some behavioral risk factors and preventive
      health practices between men and women and between Korean Americans and the total
      California population.

PMID- 9272587
TI  - Screening for curly two disease: a transatlantic perspective.

PMID- 9272586
TI  - Escherichia coli O157:H7 infections associated with eating a nationally
      distributed commercial brand of frozen ground beef patties and burgers--Colorado,
      1997.
AB  - The Colorado Department of Public Health and Environment (CDPHE) recently
      identified an outbreak of Escherichia coli O157:H7 infections associated with
      eating a nationally distributed commercial brand of frozen beef patties and
      burgers. This report describes the preliminary findings of the ongoing
      investigation of this outbreak and the product recall of six lots of Hudson Foods
      frozen ground beef patties and burgers.

PMID- 9272588
TI  - Audit of services for young people with diabetes.

PMID- 9272589
TI  - Mortality in older people with diabetes mellitus.
AB  - It is universally acknowledged that diabetes mellitus is a common cause of
      morbidity in the elderly population but it is less well established that the
      mortality of people with diabetes is greater at any given age. This comprehensive
      literature review aims to examine the evidence in order to clarify the
      relationship between diabetes and mortality risk in elderly diabetic patients.
      Information was obtained by carrying out a MEDLINE search for relevant papers
      published in 1980 and onwards; a key paper on mortality in non-insulin-dependent
      (Type 2) diabetes mellitus (NIDDM) was used as an index paper; Diabetes,
      Diabetologia, Diabetic Medicine, Diabete et Metabolisme, and Diabetes Care were
      hand searched; and, finally, other experts in the field were contacted. Two
      reviewers independently extracted the data from each of the studies and
      disagreements were discussed and resolved. The studies in elderly study
      populations comprised mainly NIDDM. The review demonstrated that diabetes is a
      significant contributor to mortality and reduced life expectancy in elderly
      subjects. Demographic trends in our population indicate that diabetes will
      continue to be a challenging health problem.

PMID- 9272590
TI  - Altered ventricular repolarization during hypoglycaemia in patients with
      diabetes.
AB  - There is circumstantial evidence implicating hypoglycaemia in the sudden
      overnight death of young patients with insulin-dependent (Type 1) diabetes
      mellitus (IDDM), the mechanism of which is unknown. We have investigated the
      effects of hypoglycaemia on the electrocardiogram in 15 patients with diabetes (8
      with IDDM and 7 with NIDDM) using a high resolution computer-based system.
      Patients were randomized to either 2 h of euglycaemia or hypoglycaemia (at around
      3 mmol l(-1)) during the afternoon, using hyperinsulinaemic glucose clamps, the
      two visits separated by a period of at least 4 weeks. Corrected QT interval
      (QTc), plasma potassium, and adrenaline were measured at baseline and at 0, 60,
      and 120 min. The degree of QTc lengthening (from baseline) during clamped
      hypoglycaemia was greater compared to the euglycaemic control period in patients
      with IDDM (median[range] at 60 min, 156[8 to 258] vs 6[-3 to 28] ms, p <0.02) and
      NIDDM (120 min, 128[16 to 166] vs 4[-3 to 169] ms, p <0.05). The fall in plasma
      potassium was greater during clamped hypoglycaemia compared to euglycaemia in
      those with NIDDM (p <0.03) but not in those with IDDM (p> 0.06). The rise in
      plasma adrenaline was greater during clamped hypoglycaemia in both groups (IDDM p
      <0.02, NIDDM p <0.02) and there was a strong relationship between the rise in
      adrenaline and increase in QTc (r = 0.73, p <0.0001). These data demonstrate
      alteration of ventricular repolarization with lengthening of the QT interval
      during hypoglycaemia and suggest a possible mechanism by which hypoglycaemia
      could cause ventricular arrhythmias.

PMID- 9272591
TI  - Effects of C-peptide on insulin-induced hypoglycaemia and its counterregulatory
      responses in IDDM patients.
AB  - Recent studies indicate that C-peptide, when given to patients with insulin
      dependent (Type 1) diabetes mellitus (IDDM), exerts significant effects on
      microvascular and neuronal functions. Adjuvant therapy with C-peptide has been
      advocated in the treatment of IDDM patients. Since endogenous insulin secretion
      is believed to be of importance for the alpha-cell function, we addressed the
      issue whether C-peptide given acutely interferes with the responses to
      hypoglycaemia. Seven IDDM patients were randomly exposed to hypoglycaemia with
      and without exogenous C-peptide. Insulin and and C-peptide were given
      intravenously in equimolar amounts for 3 hours. The decrease of blood glucose was
      faster and more pronounced during C-peptide infusion, yielding a significantly
      lower AUC 0-180 min of blood glucose (38.5 +/- 1.6 vs 44.4 +/- 2.2 mmol l(-1)h(
      1); p = 0.032). No difference between the two experiments was found concerning
      glucagon when the AUC, delta-values or levels at separate points of time were
      calculated. In conclusion, the main finding of this study was that exogenous C
      peptide, given acutely, gave rise to a more rapid onset of hypoglycaemia yielding
      no detectable differences with respect to the response of glucagon and other
      counterregulatory hormones.

PMID- 9272592
TI  - Patient awareness of genetic and environmental risk factors in non-insulin
      dependent diabetes mellitus--relevance to first-degree relatives.
AB  - Primary preventative strategies may be useful in non-insulin-dependent (Type 2)
      diabetes mellitus (NIDDM), where weight reduction and physical exercise may help
      to counteract the increased risk to first-degree relatives of affected patients.
      To assess the extent of patient's awareness of these and related issues, 100
      NIDDM patients were selected to complete a questionnaire. Forty-four per cent had
      a family history of NIDDM. Forty per cent and 35%, respectively, were aware that
      the patient's siblings and children were at an increased risk of developing
      NIDDM. Sixty-three per cent and 35%, respectively, were aware that obesity and
      physical inactivity increased the risk of developing NIDDM. After appropriate
      counselling about these risk factors, all 100 patients claimed that they would be
      advising their first-degree relatives. However, at 4 months review, 53% of
      patients had informed their first-degree relatives of the increased genetic risk
      to them. Of these patients, 83%, 74%, and 23% had provided relevant advice on
      diet, weight reduction, and physical exercise, respectively, as a means of
      reducing the risk of first-degree relatives developing NIDDM. We conclude that
      only a small proportion of patients are aware of the increased genetic
      susceptibility of their first-degree relatives to develop NIDDM and that weight
      reduction and regular physical exercise can reduce this risk. But, after
      appropriate education, a significant proportion of NIDDM patients did inform
      their close relatives of these issues and this may prove to be a useful strategy
      in the primary prevention of NIDDM.

PMID- 9272594
TI  - Association between low birthweight and high resting pulse in adult life: is the
      sympathetic nervous system involved in programming the insulin resistance
      syndrome?
AB  - To test the hypothesis that elevated sympathetic nervous system (SNS) activity
      could be determined in utero and be one of the processes mediating the link
      between size at birth and insulin resistance and raised blood pressure in adult
      life, we have studied the resting pulse rate of 449 men and women aged 46 to 54
      (mean 50) years born in Preston, Lancashire, England whose birth size was
      recorded in detail. The subjects were visited at home by trained fieldworkers who
      measured resting pulse rate and blood pressure using an automated recorder. The
      resting pulse rate ranged from 44 to 108 (mean 73) beats min(-1). It rose with
      increasing body mass index (r = 0.14, p = 0.003) and waist to hip ratio (adjusted
      for sex r = 0.10, p = 0.003) and correlated significantly with systolic and
      diastolic blood pressures (p = 0.001), fasting glucose (p = 0.02), split
      proinsulin (p = 0.001), and triglyceride concentrations (p = 0.02). The pulse
      rate fell progressively from 76 beats min(-1) among subjects who weighed 5.5 lb
      (2.5 kg) or less at birth to 71 beats min(-1) among those who weighed 7.5 lb (3.3
      kg) or more (decline in pulse rate per kg increase in birthweight = 2.7, 95 % CI
      0.6 to 4.8 beats min(-1). The association was independent of current body mass
      index, waist to hip ratio and of potential confounding variables including
      smoking, alcohol consumption, and social class. Although the resting pulse rate
      is an imperfect index of SNS activity, these findings are consistent with the
      hypothesis that elevated SNS activity established in utero is one mechanism
      linking small size at birth with the insulin resistance syndrome in adult life.

PMID- 9272593
TI  - Macrovascular disease and hyperglycaemia: 10-year survival analysis in Type 2
      diabetes mellitus: the Belfast Diet Study.
AB  - The relationship between macrovascular disease and blood glucose control in long
      term follow-up of Type 2 (non-insulin-dependent) diabetes mellitus is difficult
      to study because of the gradual rise in fasting plasma glucose due to ongoing
      beta-cell failure. We used time-dependent covariates in Cox's proportional
      hazards model to allow variables measured annually during a 10-year prospective
      follow-up to be related to risk of myocardial infarction or cerebrovascular
      accident. Data for 432 newly diagnosed diabetic patients were available, 112 of
      whom suffered myocardial infarction (fatal or non-fatal). Analysis of baseline
      measurements only gave relative hazards (95% CL) of 1.04 (0.99, 1.09) per mmol l(
      1) increase in fasting plasma glucose, 1.43 (1.12, 1.83) per decade increase in
      age and 1.07 (0.98, 1.17) per 10 % increase in percentage of ideal weight.
      Analysis incorporating ongoing measurements gave corresponding figures of 1.07
      (1.02, 1.12) for fasting plasma glucose, 1.64 (1.23, 2.20) for age and 1.06
      (0.95, 1.18) for percentage of ideal weight. The risk of myocardial infarction
      while on insulin treatment 1.09 (0.58, 2.06) or oral agents 1.41 (0.86, 2.31) was
      not significantly elevated relative to dietary treatment. Baseline smoking
      status, systolic blood pressure, and previous myocardial infarction were also
      significant predictors of myocardial infarction. Similar relationships were found
      for cerebrovascular accident and total mortality. Increasing fasting plasma
      glucose is a significant independent predictor of macrovascular disease in
      diabetes.

PMID- 9272595
TI  - Autoantibodies associated with presymptomatic insulin-dependent diabetes mellitus
      in women.
AB  - Presymptomatic autoantibody markers of insulin-dependent (Type 1) diabetes
      mellitus (IDDM) are less well characterized in adults than in children. We
      quantitated anti-GAD, anti-ICA512 and ICA by titration to endpoint and compared
      frequencies and levels in 139 Finnish women from whom 390 serum samples had been
      archived during antecedent pregnancies for 10 years before and up to 1 year after
      diagnosis of diabetes. Also, we compared the autoantibody status in adults with
      IDDM with that of children with newly diagnosed IDDM. Of the 35 women
      seropositive for 1 or more autoantibodies, 77% developed IDDM, 11% non-insulin
      dependent (Type 2) diabetes mellitus (NIDDM), 9% gestational diabetes mellitus
      requiring insulin (GDM-ins) and 3% GDM controlled by diet. The frequency of
      antibodies during the 10-year presymptomatic period was 83% for anti-glutamic
      acid decarboxylase (GAD), 52% for anti-ICA512 and 41% for islet cell antibodies
      (ICA) for those who developed IDDM, 25%, 17%, and 0% for NIDDM, 12%, 4%, and 8%
      for GDM-ins and 1%, 0%, and 1% for GDM-diet. Anti-GAD was found most consistently
      in early samples; 13 of 15 with a single autoantibody at their first test had
      anti-GAD. Among those who developed IDDM, the frequency of anti-GAD was constant,
      anti-ICA512 increased threefold, and ICA increased slightly before diagnosis.
      Levels of the autoantibodies varied between subjects, but were relatively stable
      in individual subjects. Comparison of tests on the women, and children after
      diagnosis of IDDM, showed the frequencies and levels to be the same for anti-GAD
      but lower for anti-ICA512 and ICA in adults. Our observations show in women the
      long latency of seropositivity before overt IDDM, the predominance of anti-GAD
      among these three serological markers, and the presence of these markers in NIDDM
      presumably representing a NIDDM phase of autoimmune insulitis.

PMID- 9272596
TI  - NHS acute sector expenditure for diabetes: the present, future, and excess in
      patient cost of care.
AB  - We set out to determine the present proportion of in-patient revenue used for the
      care of diabetes and its related complications and to use these data to determine
      (1) the trend in future hospital costs for the condition and (2) the excess cost
      of admissions for diabetic patients over and above that expected had these
      patients not had diabetes, using a cross-sectional descriptive study in
      conjunction with a population modelling exercise in a District Health Authority
      with a resident population of 408 000 people. The crude proportion of admissions
      for people with diabetes was 7.0% of activity in financial year 1994/5 (of 115929
      total in-patient and day case admissions). Patients with diabetes occupied 10.7 %
      of bed days and had a crude mean length of stay of 10.7 days vs 6.7 days for the
      non-diabetic group. The proportion of revenue used for their treatment was 8.7 %.
      This translated locally to 11.9 M. In year 2011 overall cost of in-patient care
      is predicted to increase by 9.4 %, however, the proportion of revenue used for
      the care of people with diabetes will increase by 15% because of age-related
      effects. The excess cost associated with treating diabetes is estimated to be 82%
      of admissions for the diabetic population, 88% of their bed days, and 86% of
      expenditure associated with their care. Most of this excess cost is associated
      with the recognised vascular complications of diabetes. We conclude that the cost
      of in-patient care for patients with diabetes is notably disproportionate to the
      population prevalence of diabetes-9 % compared to 1.36% in South Glamorgan-and
      will increase disproportionately with time. As much of the long-term morbidity is
      known to be preventable by earlier intervention, strategies should reflect the
      imperative to reduce the burden of diabetes.

PMID- 9272597
TI  - Report of the 1994 BPA/BDA Survey of Services for Children with Diabetes:
      Changing Patterns of Care. British Paediatric Association/British Diabetic
      Association.
AB  - The results of a 1994 survey of consultant paediatricians in the UK were compared
      with those of a 1988 survey to assess how the organization of services for
      children with diabetes had changed. We found evidence of a substantial
      improvement, in line with the recommendations of the 1988 BPA Working Party
      Report on the Organization of Services of Children with Diabetes. Key features of
      this improvement included a service rationalization with fewer consultants (325
      versus 360) providing care for more children: 45% with a clinic size of over 40
      children compared with 23% in 1988. More consultants saw children in a designated
      paediatric clinic (88 % compared with 63%) and expressed a special interest in
      diabetes (48% compared with 32%). Eighty-seven % of consultants had a diabetes
      nurse specialist regularly attending the clinic (vs 61% in 1988) and 91% (vs 75%)
      reported that a dietitian attended regularly. Although more consultants had a
      psychologist or psychiatrist attending the clinic, these specialists remained a
      scarce resource (20% compared with 9% in 1988). Continuing deficiencies in the
      quality of service for some children were identified with small cohorts of
      children being managed in general paediatric clinics with inadequate expert
      support staff; there was a widespread shortage of diabetes nurse specialists and
      only 30% of those in post worked full time with children. In addition 52% of
      consultants expressed no special interest in diabetes and 10% did not regularly
      monitor glycated proteins. Continuing improvement of services for children with
      diabetes in the UK is needed.

PMID- 9272598
TI  - A Survey of the Dietary Management of Children's Diabetes.
AB  - A cross-sectional survey of dietitians using a structured postal questionnaire
      was sent to 148 dietitians who provided a service to children with diabetes. One
      hundred and twenty-two (82%) replied, of whom 50 were paediatric dietitians (4
      paediatric diabetes dietitians) and 72 were other grades. One hundred and
      eighteen (97%) dietitians reviewed newly diagnosed children within 24-48 hours of
      diagnosis but only 81 (66%) used literature specifically designed for children.
      The majority 116 (95%) felt they worked within a multidisciplinary team. Only 15
      (12%) dietitians used purely qualitative carbohydrate dietary education; the
      remainder used quantitative methods, e.g. 10 g exchange system. Ninety-one (75%)
      used carbohydrate exchange lists. High fibre foods were suggested but dietitians
      felt only a moderate intake was achievable. One hundred and twelve (92%)
      recommended a reduced fat intake but guidance was not as unanimous on reducing
      specific fatty acids. Objective assessment of dietary outcomes was limited.
      Paediatric dietitians compared with other grades were more likely to use
      innovative methods of education but no other differences in dietary practice
      existed. A minority of dietitians 17 (18%) felt families would find implementing
      the diet easy. The survey confirmed national inconsistencies in dietary messages
      and poor evaluation of patient compliance. Research is required into effective
      dietary counselling to support evidence-based practice.

PMID- 9272599
TI  - Self monitoring of blood glucose in blind diabetic patients.
AB  - Blind diabetic patients face particular difficulties in blood glucose self
      monitoring (BGSM). We investigated the quality of BGSM in blind and severely
      visually impaired diabetic patients and assessed the effects of training in BGSM
      using a blood glucose meter with voice edition of values and a modified test
      strip holder for easier placement of blood samples on the strip (One Touch II
      talk (OT II)). Twenty-six insulin-treated diabetic patients (23 IDDM and 3 NIDDM)
      participated. At baseline the quality of BGSM was checked in 14 patients who
      already regularly performed BGSM without external help. Thereafter all 26
      patients received an extensive instruction in BGSM for blind patients. At re
      examination, after a mean period of 41 days, the quality of BGSM performed by the
      patients without assistance was checked in three different blood samples. Blood
      glucose was measured in the same sample by a routine laboratory method. At
      baseline the mean absolute difference between BGSM and the reference method was 
      0.3 mmol l(-1) (range; +/- SD) (-7.7-4.8; +/- 2.6 mmol l(-1)); 74% of BGSM
      measurements deviated by more than 10% from the reference values and 43% by more
      than 20%. At follow-up all 26 patients reported daily BGSM without external help.
      The mean absolute difference between BGSM and the reference method was -0.1 (-2.7
      2.8; +/- 0.9 mmol l(-1)); 25% of BGSM measurements deviated by more than 10 %
      from the laboratory reference values and 5% by more than 20%. The results of this
      study suggest that a substantial number of blind diabetic patients do not perform
      BGSM on their own at all and in those who do the reliability of the results is
      poor. However, after extensive instruction, the majority of blind diabetic
      patients should be able to perform BGSM and to obtain reliable results.

PMID- 9272600
TI  - Diabetes in British South Asians: nature, nurture, and culture.

PMID- 9272601
TI  - Diabetes in British South Asians.

PMID- 9272602
TI  - Diabetes in British South Asians.

PMID- 9272603
TI  - Effect of glycaemic control and the introduction of insulin therapy on
      retinopathy in non-insulin-dependent diabetes mellitus.

PMID- 9272604
TI  - Usefulness of the hemocue blood glucose photometer in hypoglycaemic conditions.

PMID- 9272605
TI  - Fasting plasma glucose as a screening test for diabetes mellitus.

PMID- 9272607
TI  - The postprandial state and the risk of atherosclerosis.
AB  - The results of the Diabetes Intervention Study indicate that postprandial
      hyperglycaemia, but not fasting hyperglycaemia, is an independent risk factor for
      myocardial infarction and total mortality in newly detected non-insulin-dependent
      diabetes mellitus (NIDDM). Blood pressure and triglyceride levels were also found
      to be risk factors. Data from patients in the Study to Prevent NIDDM show that
      patients with impaired glucose tolerance (IGT) have higher fasting levels of
      triglycerides, and higher fasting and postprandial levels of pro-insulin,
      insulin, and C-peptide levels, compared with those who have normal glucose
      tolerance (NGT). Postprandial data at 2 h showed that hyperinsulinaemia was
      prolonged in subjects with IGT compared with their NGT counterparts. Postprandial
      pro-insulin levels at 2 h were also increased in subjects with IGT, and were
      found to have the best discriminating power between subjects with IGT and NGT.
      Those with IGT also secreted markedly higher levels of insulin, indicated by C
      peptide levels, than those with NGT. These data support the possibility that
      subjects with IGT are at an increased risk of conditions such as atherosclerotic
      disease, even though they have not developed manifest NIDDM. Intervention with
      agents that can affect risk factors, such as triglyceride levels and postprandial
      hyperglycaemia, are expected to reduce the risk of atherosclerosis. One promising
      agent is acarbose, an antihyperglycaemic drug that significantly reduces
      postprandial insulin and triglyceride levels and has no effect on leptin levels.
      The ability of acarbose to improve glycaemic control without the potential for
      inducing hyperinsulinaemia and weight gain appears to give it an advantage over
      oral antidiabetic agents such as the sulphonylureas.

PMID- 9272608
TI  - Impaired glucose tolerance, insulin resistance and cardiovascular disease.
AB  - Non-insulin-dependent diabetes (NIDDM) is associated with a higher risk of
      cardiovascular disease (CVD) than in the non-diabetic population. The incidence
      of CVD is not, however, related to the severity or duration of disease in most
      studies, suggesting that events in the prediabetic stage can trigger CVD. Several
      factors have been linked to CVD, including hyperglycaemia, insulin resistance and
      hyperinsulinaemia. Impaired glucose tolerance (IGT), as defined by the oral
      glucose tolerance test, is a strong predictor of NIDDM. In addition, IGT and
      raised glycated haemoglobin levels are possible risk factors for CVD.
      Hyperinsulinaemia has been associated with increased cardiovascular risk, but
      this has yet to be confirmed in women. There is also evidence to link insulin
      resistance with increased cardiovascular risk, although the precise nature of
      this relationship is unclear. There are many risk factors associated with CVD
      that are probably working in concert in NIDDM. This makes assessment of risk
      posed by individual factors, such as hyperglycaemia, hyperinsulinaemia and
      insulin sensitivity, difficult.

PMID- 9272609
TI  - The postprandial state: mechanisms of glucose intolerance.
AB  - Defective carbohydrate metabolism is central to the pathogenesis of non-insulin
      dependent diabetes mellitus (NIDDM) and impaired glucose tolerance (IGT). Plasma
      glucose concentrations are determined by a balance between glucose entry into and
      removal from the circulation. In non-diabetic individuals, an oral glucose load
      triggers a rapid insulin secretory response. Insulin suppresses hepatic glucose
      release and stimulates peripheral glucose uptake, thereby limiting the
      postprandial rise in plasma glucose concentration. In addition, the term 'glucose
      effectiveness' describes how glucose regulates its own metabolism. In individuals
      with NIDDM or IGT, the beta-cell response to glucose is impaired, the incretin
      effect is reduced, hepatic and peripheral tissues are resistant to insulin, and
      glucose effectiveness may be impaired. Furthermore, disturbances in free fatty
      acid metabolism may alter intracellular glucose metabolism. The relative
      contributions of these defects to postprandial hyperglycaemia remain to be
      determined. However, the defects in insulin secretion and insulin action are
      central to understanding diabetic and prediabetic states.

PMID- 9272610
TI  - Glucose: a continuous risk factor for cardiovascular disease.
AB  - The glucose level that defines diabetes mellitus is that level above which
      patients have a high risk of eye, kidney, and neuronal disease. The risk of these
      complications rises as glucose levels increase, and decreases as therapy brings
      the glucose level down. Thus, in patients with diabetes, glucose is a continuous,
      modifiable risk factor for eye, kidney and peripheral nerve disease. Plasma
      glucose concentrations in the diabetic range are also a continuous risk factor
      for cardiovascular disease (CVD). Moreover, epidemiological evidence shows that
      the relationship between plasma glucose concentration and CVD extends well below
      the glucose level defined for diabetes and even impaired glucose tolerance. This
      continuous relationship between glucose and CVD exists in all people, not just in
      those with a defined metabolic disease, and is therefore similar to the
      relationship between cholesterol or blood pressure and CVD. It may be secondary
      to either a direct effect of elevated glucose or to some underlying metabolic
      abnormality that raises both glucose and cardiovascular risk. Whether
      interventions that lower glucose will also lower the risk of CVD is still
      unknown; the results of clinical trials are awaited.

PMID- 9272611
TI  - Acute and chronic effects of hyperglycaemia on glucose metabolism: implications
      for the development of new therapies.
AB  - Hyperglycaemia has two effects on glucose metabolism, both of which have
      implications for the development of new treatments for patients with non-insulin
      dependent diabetes mellitus (NIDDM). Acute increases in plasma glucose
      concentrations promote glucose uptake in a concentration-dependent fashion (the
      glucose mass-action effect). This increases glucose utilization in proportion to
      fasting hyperglycaemia. Postprandially, the absolute rate of glucose utilization
      is normal in patients with NIDDM, because stimulation of glucose utilization by
      glucose mass-action compensates for any defects in insulin action. These defects
      in insulin action may themselves have evolved to protect insulin-sensitive
      tissues from excessive glucose utilization during hyperglycaemia. Because the
      absolute rate of glucose utilization is normal in NIDDM, excessive postprandial
      hyperglycaemia can be attributed to diminished suppression of endogenous glucose
      production. Consequently, suppression of endogenous glucose production, both in
      the fasting and postprandial states, becomes the primary target for therapy.
      Chronically, hyperglycaemia impairs both insulin secretion and sensitivity, a
      phenomenon known as 'glucose toxicity'. This phenomenon explains why any
      therapeutic intervention, diet, insulin or drugs, improves both insulin secretion
      and action. Glucose toxicity may also contribute to the progressive worsening of
      hyperglycaemia that characterizes the natural course of NIDDM.

PMID- 9272612
TI  - Diabetes and atherosclerosis--a lipoprotein perspective.
AB  - Atherosclerosis is the most frequent complication of diabetes. It affects all
      major vascular beds. The metabolic derangements that occur in diabetes may
      underlie many of the reasons for this. These abnormalities include alterations in
      the metabolism of lipoproteins, particularly the triglyceride-rich lipoproteins.
      Studies are currently being conducted to determine whether correcting the
      dyslipoproteinaemias associated with diabetes will reduce the risk of
      atherosclerosis in the diabetic population.

PMID- 9272613
TI  - Acute hyperglycaemia and oxidative stress generation.
AB  - Oxidative stress is an acknowledged pathogenic mechanism in diabetic
      complications. Several studies have demonstrated that acute hyperglycaemia can
      impair the physiological homeostasis of important systems in living organisms and
      that it may exert these effects via production of free radicals and associated
      oxidative stress. Acute increases in plasma glucose concentration may increase
      free radical production by the following mechanisms: labile glycation; auto
      oxidation of glucose; and intracellular activation of the polyol pathway, which
      produces an imbalance in the NADH/NAD+ ratio and favours the production of free
      radicals. The hypothesis that free radicals may mediate the effects of acute
      hyperglycaemia is supported by evidence that antioxidants can counteract some of
      the effects induced by acute hyperglycaemia, for example, vasoconstriction,
      activation of coagulation, and the increase in plasma intracellular adhesion
      molecule-1 concentrations. Direct evidence of an association between oxidative
      stress and hyperglycaemia has come from studies of induced hyperglycaemia or
      standardized meal intake. In both diabetic and non-diabetic subjects,
      hyperglycaemia or meal intake causes a reduction in plasma Total Radical-trapping
      Antioxidant Parameter (TRAP). This is associated with consumption of protein
      thiol groups, vitamin C, and uric acid. This may confirm the hypothesis that
      acute hyperglycaemia provokes oxidative stress, which destroys the natural
      antioxidant defences found in the plasma.

PMID- 9272614
TI  - Postprandial glucose and vascular disease.
AB  - The high plasma glucose concentrations in patients with diabetes are associated
      with an increased risk of vascular disease. In patients with non-insulin
      dependent diabetes mellitus, vascular changes often predate clinical diagnosis of
      hyperglycaemia. Impaired glucose tolerance precedes diabetes and may therefore be
      an important phase in the development of vascular changes. There is evidence to
      suggest that hyperglycaemia interferes with the activity and function of
      endothelial cells. In vitro data show that high glucose concentrations can
      activate protein kinase C (PKC) in endothelial cells, specifically PKC alpha.
      This activation appears to stimulate expression of adhesion molecules on
      endothelial cells, facilitating the adhesion and uptake of leukocytes into the
      endothelium. In addition, high glucose concentrations affect the permeability of
      tight junctions between endothelial cells, which also seems to be mediated by
      PKC. Thus, PKC activation may be central to the effects of glucose-stimulated
      vascular changes. Evidence for direct stimulation of endothelial cells by glucose
      may support the hypothesis that postprandial glucose spikes are important in the
      early development of micro- and macrovascular disease.

PMID- 9272615
TI  - Phenotyping and genotyping patients with cardiovascular risk factors.
AB  - Complex diseases require precise phenotyping if their genetic basis is to be
      properly understood. This process is more complex than the analysis used for
      monogenic diseases. Collecting family phenotypic data is costly and time
      consuming, making such studies difficult. We have developed a family-oriented,
      field working approach that relies on index patients, their primary-care
      physicians, and a minimum number of field working staff. The index patients
      recruit family members by distributing packs containing the materials necessary
      for participation. Computer analysis of the data returned enables construction of
      the medical family tree. We have extended this genetic field working approach to
      patients with lipid disorders, arterial hypertension, non-insulin-dependent
      diabetes mellitus, and the 'Metabolic Syndrome'. Data from these groups can be
      used to identify susceptibility genes for premature arteriosclerosis. We describe
      a cost-effective methodology that can be used in the primary-care setting to
      identify 'at-risk' patients and facilitate effective targeting of limited health
      care resources.

PMID- 9272616
TI  - Mechanisms of postprandial hyperlipidaemia--remnants and coronary artery disease.
AB  - High plasma concentrations of triglyceride-rich lipoprotein are associated with
      an increased risk of coronary artery disease (CAD). In the postprandial state,
      there is a large increase in chylomicron and very low-density lipoprotein (VLDL)
      concentrations. The accumulation of potentially atherogenic particles is
      controlled by the balance of their synthesis and clearance. Chylomicrons are rich
      in triglyceride and secreted by the intestine postprandially. Chylomicrons
      compete with VLDL for hydrolysis by lipoprotein lipase (LPL). This competition
      may cause the increase in large plasma concentration of VLDL seen in the
      postprandial state. Postprandial increases in atherogenic plasma lipoprotein
      concentrations are accentuated in insulin-resistant states. Insulin resistance is
      associated with greater flux of free fatty acids, which may in turn lead to
      enhanced synthesis of VLDL. Alimentary lipidaemia has been shown to effect
      changes in the coagulation cascade which may provide additional connections
      between postprandial lipaemia and CAD. Thus, specific postprandial changes in
      plasma lipids may be indicative of atherogenic risk. Measurement of postprandial
      plasma triglyceride concentration and the apo B-48 and apo B-100 contents in
      triglyceride-rich lipoprotein fractions are probably useful indicators of
      postprandial dyslipidaemia, but prospective studies of how these lipid variables
      relate to CAD progression are needed.

PMID- 9272617
TI  - Postprandial lipoproteins in non-insulin-dependent diabetes mellitus.
AB  - People with non-insulin-dependent diabetes mellitus (NIDDM) have a higher
      incidence of cardiovascular disease (CVD) than the non-diabetic population. In
      addition, NIDDM patients have a spectrum of lipid abnormalities that may confer
      an increased risk of developing CVD. The pattern of dyslipidaemia seen in NIDDM
      patients is different from that seen in the non-diabetic population. This
      suggests that patients with NIDDM may need different lipid-lowering treatment
      from that used in the non-diabetic population. In the post-absorptive state,
      secretion of very low-density lipoprotein (VLDL) is higher in patients with
      NIDDM, possibly because of the impaired ability of insulin to inhibit lipolysis
      and to reduce hepatic VLDL secretion. Clearance of triglyceride-rich lipoproteins
      is also important in determining the extent of postprandial hyperlipidaemia.
      Lipoprotein lipase (LPL) reduces plasma lipoprotein concentration via several
      mechanisms. In patients with NIDDM, the capacity of LPL to minimize postprandial
      hyperlipidaemia may be reduced, although the pathophysiological basis of this is
      not known. Other changes in patients with NIDDM, such as modifications to
      cholesteryl ester transfer protein (CETP) and hepatic lipase activity, may also
      affect postprandial lipaemia but such effects are probably secondary to
      alterations in lipoprotein clearance. Present evidence suggests that postprandial
      hyperlipidaemia is atherogenic. There are, however, little specific data from
      patients with NIDDM. More studies are therefore needed to establish the optimal
      treatment of dyslipidaemia in patients with NIDDM.

PMID- 9272618
TI  - Mechanisms of hepatic chylomicron remnant clearance.
AB  - Experimental evidence suggests that chylomicron remnants, the carriers of dietary
      lipids, are highly atherogenic and that their postprandial plasma concentration
      is directly correlated with the progression of coronary artery disease. Much
      interest has therefore focused on elucidation of the various steps involved in
      uptake of these lipoprotein particles from the circulation. Recently, gene
      targeting has been applied to generate mouse models with deficiencies in
      lipoprotein metabolism and to dissect the chylomicron remnant clearance pathway
      in vivo. These experiments, together with studies performed in cultured cells,
      have demonstrated that plasma clearance of chylomicron remnants is a two-step
      process. The lipoprotein particles are rapidly sequestered in the liver by
      binding to the heparan sulphate proteoglycan surface (HSPG) of hepatocytes. This
      constitutes a high-capacity reservoir for adsorbing large amounts of lipoproteins
      in the postprandial state. Binding to HSPG is facilitated by apolipoprotein E
      (apo E) molecules present on the surface of the remnant particles. Once bound to
      the hepatocellular surface, the remnants are further enriched with apo E secreted
      by the hepatocytes. They are then internalized by two lipoprotein receptors: the
      low-density lipoprotein (LDL) receptor and the LDL receptor-related protein
      (LRP). Characterization of this distinct clearance pathway for chylomicron
      remnants helps to direct further research towards developing an understanding of
      pathological abnormalities in postprandial lipoprotein metabolism.

PMID- 9272619
TI  - The effects of tachykinins on inflammatory and immune cells.
AB  - The aim of this article is to provide an up-dated overview of the available
      information on the role played by tachykinins in recruiting/regulating the
      function of immune/inflammatory cells, an issue which has received considerable
      input from the recent availability of potent and selective antagonists for
      tachykinin receptors. It appears that NK1 receptors play a role in mediating the
      extravascular migration of granulocytes into inflamed tissues in response to
      various inflammatory stimuli, although this effect may not be due to the
      expression of NK1 receptors by granulocytes themselves. Several data also imply a
      role for NK1 and NK2 receptors in regulating immune function. No data are
      available to suggest the expression of NK3 receptors by inflammatory/immune
      cells. Mast cell degranulation by substance P appears to be a non-receptor
      dependent response which may take place in vivo during intense stimulation. An
      emerging concept in the field relates to the ability of certain immune cell types
      to synthesize and possibly release tachykinins. Immune cells could represent an
      additional source of tachykinins in inflamed tissues, providing a non-neurogenic
      tachykininergic contribution to the local inflammatory process.

PMID- 9272620
TI  - Endothelin-3 reduces C-type natriuretic peptide-induced cyclic GMP formation in
      C6 glioma cells.
AB  - The effect of endothelin-3 (ET-3) on C-type natriuretic peptide (CNP)-induced
      guanosine 3',5'-cyclic monophosphate (cGMP) was examined in C6 glioma cells, CNP
      induced cGMP formation was both time- and dose-dependent, with an EC50 value of
      about 10 nM. While ET-3 and phorbol 12-myristate 13-acetate (PMA) had no effect
      on basal cGMP production, both compounds were potent inhibitors of CNP-induced
      cGMP formation, with IC50 values of approximately 10 and 2 nM, respectively.
      Although protein kinase C (PKC) inhibitors had no effect on basal cGMP formation,
      Ro 31-8220, a PKC inhibitor, reversed the ET-3 inhibition on CNP-induced cGMP
      formation by 63% and that of PMA almost completely. Our findings suggest that
      stimulation of cGMP formation by CNP in C6 glioma cells is negatively modulated
      by PKC activation, and that the inhibitory action of ET-3 on CNP-stimulated cGMP
      formation is mediated partly by PKC.

PMID- 9272621
TI  - CCK-resistance in Zucker obese versus lean rats.
AB  - Obese Zucker rats are less sensitive to the satiety effect of CCK than lean
      litter mates. The present studies further characterised this CCK resistance.
      Subcutaneous injection of the CCK agonist caerulein dose-dependently decreased
      food intake in Zucker obese and lean rats whereas the CCK-B agonist gastrin-17
      did not. Caerulein at 4 microg/kg, which resulted in CCK plasma bioactivity
      slightly above postprandial levels, decreased food intake in lean rats but not in
      obese rats. The decrease in food intake was also more marked at higher caerulein
      doses (20-100 microg/kg) in lean versus obese rats. In lean animals the satiety
      effects of the "near physiological" 4 microg/kg caerulein dose was abolished
      after blockade of vagal afferents with capsaicin, whereas the effects of higher
      caerulein doses were not. CCK-stimulated amylase secretion from pancreatic acini
      and binding capacity of 125I-labelled CCK-8 were decreased in obese versus lean
      rats. The CCK-A antagonist loxiglumide at 20 mg/kg, a dose which abolished the
      action of all caerulein doses on food intake, failed to alter the food intake
      either in obese or in lean rats when given without an agonist. The results
      suggest that the satiety effects of "near physiological" doses of caerulein in
      lean rats are mediated by vagal afferents whereas pharmacological doses act via
      non-vagal mechanisms. The differences in CCK's satiety effect between lean and
      obese rats may be due to differences in CCK-receptor binding and action at
      peripheral vagal sites. However, the failure of the CCK-A antagonist to increase
      food intake questions whether any of the effects of exogenous CCK are of
      physiological relevance.

PMID- 9272622
TI  - Excitatory action of angiotensins II and IV on hippocampal neuronal activity in
      urethane anesthetized rats.
AB  - The renin-angiotensin system of the mammalian brain seems to interfere with the
      process of cognition and has been associated with the hippocampal function in
      relation to mechanisms of learning and memory. In our investigation, the effects
      of angiotensin II (Ang II) and angiotensin IV (Ang II) on neuronal activity have
      been studied in the hippocampus of adult rats anesthetized with urethane.
      Excitatory effects of both angiotensins predominated over inhibitory effects.
      Angiotensins also induced an enhancement of burst discharges. These angiotensin
      induced effects were blocked by the specific angiotensin antagonists. Our
      findings showed that the different effects of Ang II and Ang IV in behavioral
      studies are not similarly reflected in a different change of the discharge rate
      and/or pattern of hippocampal neurons after microiontophoretic administration of
      both substances.

PMID- 9272623
TI  - Synthesis, solution structure, binding activity, and cGMP activation of human
      guanylin and its disulfide isomer.
AB  - Guanylin is a recently isolated peptide consisting of 15 amino acid residues with
      four cysteines, which may form two intramolecular disulfide bridges, and
      stimulates intestinal membrane guanylate cyclase. The position of the disulfide
      linkages of guanylin was predicted from its structural similarity to a heat
      stable enterotoxin which is thought to be responsible for secretory diarrhoea.
      Both guanylin, with disulfide positions 4-12 and 7-15, and its disulfide isomer,
      with disulfides positions 4-15 and 7-12, were chemically synthesized by the solid
      phase method and purified. Two specific disulfides were selectively formed and
      confirmed by sequencing, mass spectrometry and high-performance liquid
      chromatography in combination with enzymatic cleavage. The structure of both
      isomers has been investigated in solution by 1H nuclear magnetic resonance
      spectroscopy. Guanylin exists as a mixture of two stable conformations which have
      compact spiral structures, from comparison with literature data. In contrast, the
      disulfide isomer of guanylin shows only a single conformation with an elongated
      curved plate-like structure. Binding assays were performed using labelled
      guanylin with membranes obtained from rat jejunum. Both disulfide isomers were
      investigated by the cGMP assay. Both binding and cGMP assays indicated that the
      relevant form of disulfide bridges in the intact guanylin was as predicted.

PMID- 9272624
TI  - Expression of the chromogranin A-derived peptides pancreastatin and WE14 in rat
      stomach ECL cells.
AB  - The ECL cells constitute the predominant endocrine cell population in the mucosa
      of the acid-secreting part of the stomach (fundus). They are rich in chromogranin
      A (CGA), histamine and histidine decarboxylase (HDC). They secrete CGA-derived
      peptides and histamine in response to gastrin. The objective of this
      investigation was to examine the expression of pancreastatin (rat CGA266-314) and
      WE14 (rat CGA343-356) in rat stomach ECL cells. The distribution and cellular
      localisation of pancreastatin- and WE14-like immunoreactivities (LI) were
      analysed by radioimmunoassay and immunohistochemistry with antibodies against
      pancreastatin, WE14 and HDC. The effect of food deprivation on circulating
      pancreastatin-LI was examined in intact rats and after gastrectomy or fundectomy.
      Rats received gastrin-17 (5 nmol/kg/h) by continuous intravenous infusion or
      omeprazole (400 micromol/kg) once daily by the oral route, to induce
      hypergastrinemia. CGA-derived peptides in the ECL cells were characterised by gel
      permeation chromatography. The expression of CGA mRNA was examined by Northern
      blot analysis. Among all of the endocrine cells in the body, the ECL cell
      population was the richest in pancreastatin-LI, containing 20-25% of the total
      body content. Food deprivation and/or surgical removal of the ECL cells lowered
      the level of pancreastatin-LI in serum by about 80%. Activation of the ECL cells
      by gastrin infusion or omeprazole treatment raised the serum level of
      pancreastatin-LI, lowered the concentrations of pancreastatin- and WE14-LI in the
      ECL cells and increased the CGA mRNA concentration. Chromatographic analysis of
      the various CGA immunoreactive components in the ECL cells of normal and
      hypergastrinemic rats suggested that these cells respond to gastrin with a
      preferential release of the low-molecular-mass forms.

PMID- 9272625
TI  - Effect of cholecystokinin and gastrin on human peripheral blood lymphocyte
      functions, implication of cyclic AMP and interleukin 2.
AB  - The effects in vitro of sulphated and desulphated cholecystokinin (CCK)-8, and of
      gastrin-17 and gastrin-34 were studied at concentrations from 10(-14) M to 10(-6)
      M on several functions of human peripheral blood lymphocytes, i.e.: adherence to
      substrate, mobility (spontaneous and directed by a chemical gradient or
      chemotaxis), and spontaneous and phytohaemagglutinin (PHA)-mediated
      proliferation. All peptides, at concentrations from 10(-10) M to 10(-8) M,
      inhibited significantly the mobility capacity and PHA-induced proliferation, and
      increased the adherence and spontaneous proliferation. A dose-response
      relationship was observed, with a maximum response of lymphocyte functions at 10(
      10) M. These peptides induced a significant increase of intracellular cAMP levels
      at 30 and 60 sec. Because lymphoproliferation requires production of interleukin
      2 (IL-2) by lymphocytes, we also measured the IL-2 production in the presence of
      the CCK and gastrin peptides, finding that this production was higher than in the
      respective controls. When peptides were added to samples containing PHA, the IL-2
      production was significantly decreased with respect to samples incubated with PHA
      alone. These results suggest that the CCK and gastrin peptides are negative
      modulators of lymphocyte mobility (spontaneous mobility and chemotaxis), causing
      an inhibition of these activities through an increase of intracellular cAMP
      levels, and of PHA-induced lymphoproliferation, which is mediated by a diminution
      of the IL-2 production by lymphocytes.

PMID- 9272626
TI  - Transient transcriptional activation of gastrin during sodium butyrate-induced
      differentiation of islet cells.
AB  - Transient expression of pancreatic gastrin corresponds to a period of rapid islet
      cell development. After birth gastrin expression silencing is coincidental with
      islet cell terminal differentiation, while persistent expression is accompanied
      with nesidioblastosis and reexpression observed in islet cell tumors. Experiments
      with transgenic animals suggested that gastrin might act synergistically with
      growth factors to stimulate islet cell development. The present study intended to
      establish an in vitro cell culture model to analyse the molecular events
      controlling gastrin gene activation and repression dependent on islet cell
      differentiation. Sodium butyrate, a proliferation-arresting compound has
      previously been shown to differentiate insulinoma cells while increasing insulin
      production. The present paper demonstrates concomitant transient increase in
      gastrin mRNA, intracellular and secreted gastrin during sodium butyrate
      treatment. Increased gastrin expression was due to activation or derepression of
      gastrin promoter activity as revealed by promoter analyses. This in vitro model
      mimics the expression pattern of gastrin and insulin observed during fetal islet
      cell development and provides an excellent tool to analyse the molecular
      mechanisms controlling gastrin gene activation and selective repression during
      islet cell differentiation.

PMID- 9272627
TI  - Neuropeptide Y1 receptors in the rat genital tract.
AB  - Using in situ hybridization and immunohistochemistry, the expression of type 1
      neuropeptide Y (NPY) receptors (Y1-Rs) has been demonstrated in the rat genital
      tract. In the male Y1-R mRNA and Y1-R-like immunoreactivity (LI) were found in
      smooth muscles of predominantly arterioles and small arteries inside testis.
      Fibers showing NPY-LI could not be detected within testis but only in the tunica
      albuginea. These Y1-Rs are suggested to mediate vasoconstriction, possibly
      activated by NPY released from nerves in the tunica albuginea. In the female rat
      Y1-R mRNA, but not Y1-R-LI was found in vascular smooth muscles of arteries in
      the ovary and oviduct. In the oviduct Y1-R mRNA was also detected in the non
      vascular smooth muscle layer. Fibers showing NPY-LI were found around blood
      vessels both in the ovary and oviduct. In the female genital tract also Y1-Rs may
      thus be involved in regulatory mechanisms mediating, for example,
      vasoconstriction.

PMID- 9272628
TI  - Comparison of responses to rat and human adrenomedullin in the hindlimb vascular
      bed of the cat.
AB  - Responses to rat (r) adrenomedullin (ADM) and human (h) ADM were compared in the
      hindlimb vascular bed of the cat under conditions of controlled blood flow. Intra
      arterial injections of rADM and hADM in doses of 0.03-1 nmol caused dose-related
      decreases in hindlimb perfusion pressure. In terms of relative vasodilator
      activity, rADM was similar to hADM. The time course of the vasodilator response
      and the recovery half times (T1/2) for the vasodilator response to rADM and hADM
      were not significantly different. Decreases in hindlimb perfusion pressure in
      response to rADM and hADM were not altered by the calcitonin gene-related peptide
      receptor antagonist, rCGRP(8-37), at the same time, vasodilator responses to
      calcitonin gene-related peptide (CGRP) were significantly reduced. The T1/2 of
      the vasodilator response to rADM and hADM were significantly greater after
      administration of the cAMP-selective, type IV phosphodiesterase inhibitor,
      rolipram. These data demonstrate that decreases in hindlimb perfusion pressure in
      response to rADM and hADM are similar and that vasodilator responses to rADM are
      not dependent on the activation of CGRP receptors in the hindlimb vascular bed of
      the cat. These data further suggest that decreases in hindlimb perfusion pressure
      in response to rADM are mediated by smooth muscle increases in cAMP levels.

PMID- 9272629
TI  - Hyperpolarization-activated Cl- current elicited by pituitary adenylate cyclase
      activating polypeptide in Xenopus oocytes.
AB  - We examined the electrophysiological effect of pituitary adenylate cyclase
      activating polypeptide (PACAP) in isolated Xenopus laevis oocytes in vitro. In
      conventional two-electrode voltage clamp experiments, PACAP (1-10 microM)
      activated an inward rectifier current at membrane potentials more negative than 
      60 mV without causing any significant change in currents at potentials more
      positive than -60 mV both in the follicle-enclosed oocyte and in the
      defolliculated oocyte. This current reversed at -22.5 mV, close to the
      theoretical value of Cl- equilibrium potential and the reversal potential of this
      current was shifted positively by reducing [Cl-]o. This current was blocked by Cl
      channel blocker SITS and Ba2+. Furthermore, VIP and adenylate cyclase activator
      forskolin did not elicit the currents. In conclusion, PACAP elicited the
      hyperpolarization-activated Cl- current in Xenopus laevis oocytes. This current
      may modulate the membrane potential of the oocyte, thereby affecting the oocyte
      physiology.

PMID- 9272630
TI  - Thyrotropin releasing hormone prevents abnormalities of cortical acetylcholine
      and monoamines in mice following head injury.
AB  - We investigated the effects of thyrotropin releasing hormone (TRH) on changes in
      cortical concentrations of acetylcholine (ACh) and monoamines produced by
      concussion in mice. Concussion was induced by dropping a metal rod on the head,
      and the concentration of ACh, norepinephrine (NE), dopamine (DA) and serotonin (5
      HT) in the cerebral cortex were measured by HPLC. We also examined the arousal
      effects of 0.5 mg/kg of TRH and 0.015 mg/kg of L-pyro-2-aminoadipyl-histidyl
      thiazolidine-4-carboxamide (MK-771), a TRH analogue, injected intraperitoneally
      10 min before concussion, on neurotransmitter concentrations. Mice were
      sacrificed at 25 (representing the righting reflex time) and 210 s (representing
      spontaneous movement time). At 25 s after concussion, the concentration of ACh
      was significantly higher than in control mice, but pretreatment with TRH and MK
      771 prevented the rise in ACh. In contrast, head injury significantly reduced NE
      concentration. TRH and MK-771 also prevented the fall in NE. Concussion did not
      change cortical concentrations of DA and 5-HT. Our results suggest that
      disturbances of consciousness produced by concussion may be due to increased ACh
      and diminished NE in the cerebral cortex. Our findings also suggest that the
      arousal effects of TRH on concussion-induced disturbances of consciousness are
      due to normalization of cortical cholinergic and noradrenergic neuronal systems.

PMID- 9272631
TI  - Leptin suppresses basal insulin secretion from rat pancreatic islets.
AB  - The effects of leptin on insulin secretion from pancreatic islets of Sprague
      Dawley rats were examined in vitro. In a basal glucose medium (5.5 mM), insulin
      secretion from isolated islets was significantly decreased after addition of a
      recombinant leptin (80 nM) (3.20+/-0.14 nmol/10 islets/h) compared with that
      before the addition (4.41+/-0.30 nmol/10 islets/h). Although significant leptin
      suppression of insulin secretion was not observed under a glucose-stimulated
      (11.1 mM) condition, these results suggest that a negative feedback system may
      exist between leptin and insulin, which increases the production of leptin from
      adipose tissues.

PMID- 9272632
TI  - Developmental gene expression of gastrin receptor in rat stomach.
AB  - Gastrin, which is present in fetal plasma, may have important roles in the
      development of gastric mucosa, since it is not only a potent stimulator of
      gastric acid secretion but also a growth promoting factor. Gastrin regulates
      various cellular functions via its receptors on cell membrane. Therefore, in
      order to elucidate a role for gastrin in the development of gastrointestinal
      system during gestation, Northern blot analysis was performed. The results of the
      study suggested that gastrin receptor is mainly present on parietal cells.
      Furthermore, proton pump and gastrin receptor gene expressions in parietal cells
      were strongly stimulated by the administration of exogenous gastrin. In
      conclusion, gastrin may be involved in the developmental change of parietal cells
      through its receptors.

PMID- 9272633
TI  - Identification of amidated forms of GLP-1 in rat tissues using a highly sensitive
      radioimmunoassay.
AB  - The development of a sensitive radioimmunoassay (RIA) for C-terminally amidated
      forms of glucagon-like peptide-1 (GLP-1) is described. Rabbits immunized with GLP
      1(7-36)amide conjugated to bovine serum albumin with glutaraldehyde produced
      antisera containing high-affinity antibodies directed against an epitope that
      included the free amidated C-terminus of the peptide. These antisera could be
      used in a sensitive RIA (detection limit 0.1 fmol/tube) that measured GLP-1(7
      36)amide and GLP-1(1-36)amide equally. Total concentrations of amidated GLP-1
      immunoreactivity in extracts of rat hypothalamus, pancreas and intestine were
      determined by RIA, and resolved into GLP-1(7-36)amide, GLP-1(1-36)amide and
      unidentified cross-reacting substances by HPLC. Whereas only GLP-1(7-36)amide
      could be identified in the hypothalamus, in amounts that represented 55-94% of
      total glucagon-like immunoreactivity (GLI), the pancreas produced chiefly GLP-1(1
      36)amide, representing 0.8-3.4% of total GLI, and only trace or undetectable
      amounts of GLP-1(7-36)amide (0-0.36% of total GLI). This argues against any role
      of intrapancreatic GLP-1(7-36)amide in the secretion of insulin. In the terminal
      ileum total amidated GLP-1 immunoreactivity represented 27-73% of total GLI, and
      in five of six specimens only GLP-1(7-36)amide could be identified on HPLC, in
      amounts representing 13-17% of total GLI. Only one specimen of terminal ileum
      contained HPLC-identified GLP-1(1-36)amide (13% of total GLI) in addition to GLP
      1(7-36)amide (31% of total GLI). Acid-ethanol extraction of peptide-free rat
      plasma with added GLP-1(7-36)amide gave recoveries of 91+/-SEM 2% in the range 20
      200 pmol/l. Basal plasma amidated GLP-1 in six unanaesthetized rats was 4.1+/-1.1
      pmol/l and rose to a maximum of 15.4+/-3.0 pmol/l 10 min after intragastric
      glucose 1 g/kg, illustrating the modest level of plasma responses of amidated
      forms of GLP-1.

PMID- 9272634
TI  - Endocrine function of neuropeptide Y knockout mice.
AB  - Among its many proposed functions, neuropeptide Y (NPY) is thought to modulate
      the hypothalamic-pituitary axis. Specifically, increased hypothalamic NPY
      signaling may be critical in mediating the neuroendocrine response to fasting. To
      determine the consequences of NPY deficiency on endocrine physiology, multiple
      hormones were quantitated in wildtype and NPY-knockout mice under fed and fasted
      conditions. Serum concentrations of leptin, corticosterone, thyroxine, and
      testosterone were normal in NPY-knockout males fed ad libitum. A 48-hour fast
      resulted in a 50% reduction in leptin, a 60% reduction in thyroxine, a 75%
      reduction in testosterone, and a 12-fold increase in corticosterone in both
      wildtype and NPY-knockout mice. Fasting also increased the estrous cycle length
      by 3 days in both wildtype and NPY-deficient female mice. We conclude that NPY is
      not essential for appropriate function of the gonadotropic, thyrotropic, or
      corticotropic axes under ad lib fed conditions or in response to acute fasting.

PMID- 9272635
TI  - Demyelination induced by protein kinase C-activating tumor promoters in
      aggregating brain cell cultures.
AB  - The plasticity of mature oligodendrocytes was studied in aggregating brain cell
      cultures at the period of maximal expression of myelin marker proteins. The
      protein kinase C (PKC)-activating tumor promoters mezerein and phorbol 12
      myristate 13-acetate (PMA), but not the inactive phorbol ester analog 4alpha-PMA,
      caused a pronounced decrease of myelin basic protein (MBP) content and 2',3'
      cyclic nucleotide 3'-phosphohydrolase (CNP) activity. In contrast,
      myelin/oligodendrocyte protein (MOG) content was affected relatively little.
      Northern blot analyses showed a rapid reduction of MBP and PLP gene expression
      induced by mezerein, and both morphological and biochemical findings indicate a
      drastic loss of compact myelin. During the acute phase of demyelination, only a
      relatively small increase in cell death was perceptible by in situ end labeling
      and in situ nick translation. Basic fibroblast growth factor (bFGF) also reduced
      the levels of the oligodendroglial differentiation markers and enhanced the
      demyelinating effects of the tumor promoters. The present results suggest that
      PKC activation resulted in severe demyelination and partial loss of the
      oligodendrocyte-differentiated phenotype.

PMID- 9272636
TI  - Developmental expression of the murine Mobp gene.
AB  - In this report we describe the developmental expression of the murine (Mobp) gene
      encoding myelin-associated oligodendrocytic basic protein. We have characterized
      three Mobp cDNA clones which have been used as probes. Murine Mobp splice variant
      1 (mmsv-1), a portion of 3' untranslated region (UTR), is homologous to 3' UTR
      sequences found in the rat Mobp splice variants rOP1, Mobp81-A and Mobp-99. The
      mmsv-2 sequence, encoding 81 amino acids, closely resembles the rat Mobp81-A
      splice variant. The mmsv-3 cDNA, encoding 170 amino acids corresponding closely
      to the rat rOPRP1 splice variant, detects a single mRNA species present in low
      levels from E12 onward, suggesting this MOBP may have a function alternative or
      additional to involvement in myelin formation. The mmsv-1 probe detects an mRNA
      species abundantly expressed in the postnatal central nervous system (CNS) but
      barely detectable at E18. This mRNA is located initially in the cell bodies of
      oligodendrocytes, moving distally into their processes as myelination proceeds.
      The most abundant mmsv(s) in the adult CNS are present at detectable levels after
      expression of the myelin basic protein (Mbp) gene and marginally after or
      coincident with the proteolipid protein (Plp) gene. The level of the abundant,
      late-expressed mRNA correlates closely with the capacity to form myelin and the
      maturity of oligodendrocytes, as shown in two hypomyelinated mutants, rumpshaker
      and jimpy, which represent mildly and severely affected phenotypes, respectively.

PMID- 9272637
TI  - Molecular cloning and characterization of a novel mRNA present in the squid giant
      axon.
AB  - Previously, we reported the presence of a heterogeneous population of mRNAs in
      the squid giant axon. The construction of a cDNA library to this mRNA population
      has facilitated the identification of several of the constituent mRNAs which
      encode several cytoskeletal and motor proteins as well as enolase, a glycolytic
      enzyme. In this communication, we report the isolation of a novel mRNA species
      (pA6) from the axonal cDNA library. The pA6 mRNA is relatively small (550
      nucleotides in length) and is expressed in both nervous tissue and skeletal
      muscle. The axonal localization of pA6 mRNA was unequivocally established by in
      situ hybridization histochemistry. The results of quantitative RT-PCR analysis
      indicate that there are 1.8 x 10(6) molecules of pA6 mRNA (approximately 0.45 pg)
      in the analyzed segment of the giant axon and suggest that the level of pA6 mRNA
      in the axonal domain of the giant fiber system might be equal to or greater than
      the level present in the parental cell soma. Sequence analysis of pA6 suggests
      that the mRNA encodes an integral membrane protein comprising 84 amino acids. The
      putative protein contains a single transmembrane domain located in the middle of
      the molecule and a phosphate-binding loop situated near the N terminus. The C
      terminal region of the protein contains two potential phosphorylation sites.
      These four structural motifs manifest striking similarity to domains present in
      the ryanodine receptor, raising the possibility that pA6 represents a cephalopod
      intracellular calcium release channel protein.

PMID- 9272638
TI  - Individual isoforms of the amyloid beta precursor protein demonstrate
      differential adhesive potentials to constituents of the extracellular matrix.
AB  - The amyloid beta precursor protein (AbetaPP) can exist as a membrane-bound
      glycoprotein which modulates neural cell adhesion. The adhesion of clones of the
      AtT20 mouse pituitary cell line, transfected with cDNA coding for the 695
      (AbetaPP695) and 751 (AbetaPP751) amino acid forms of the protein, to individual
      components of the extracellular matrix was determined using a centrifugal shear
      assay. On laminin, poly-L-lysine, fibronectin, and uncoated glass substrata, the
      cells transfected with AbetaPP695 (6A1 cells) demonstrated a 50% increase in
      adhesivity over nontransfected cells, while those transfected with AbetaPP751
      (7A1 cells) showed a significant decrease in adhesion. There was, however, a
      significant increase in the adhesive strength of the 7A1 cells to collagen type
      IV with no change in the adhesivity of the 6A1 cells when compared with control.
      These changes in adhesivity could be attributed to changes in the levels of the
      membrane-bound protein and were not due to the interaction of soluble AbetaPP
      with elements of the extracellular matrix. These studies provide evidence for
      differential adhesivities of the constituent AbetaPP isoforms and the possible
      role of the Kunitz protease inhibitor (KPI) domain in influencing the adhesive
      properties of the protein backbone.

PMID- 9272639
TI  - Developmentally regulated masking of an intracellular epitope of the 180 kDa
      isoform of the neural cell adhesion molecule NCAM.
AB  - The neural cell adhesion molecule NCAM is a cell surface glycoprotein that occurs
      in several isoforms. It was previously shown that the largest 180-kDa isoform of
      NCAM (NCAM 180) accumulates at sites of cell contact and in postsynaptic
      densities and may be responsible for the stabilization of cell contacts by its
      interaction with the membrane-cytoskeleton linker protein brain spectrin. In
      immunohistochemical studies on the expression of the NCAM 180, we noticed that
      two NCAM 180 specific monoclonal antibodies, termed 481 and D3, showed different
      patterns of immunoreactivity in sections of fresh-frozen adult mouse brain. Here
      we show that the D3-specific, but not the 481-specific epitope becomes
      inaccessible to the antibody during development of the hippocampal formation,
      coincident with the establishment of stable cell-cell contacts. In contrast, in
      the olfactory bulb with its continually regenerating olfactory nerve fibers, both
      NCAM 180 antibodies remain fully immunoreactive throughout development and
      adulthood. We also show that the D3-specific epitope becomes inaccessible in
      primary cerebellar neuron cultures with time in culture. Electrophoretic
      separation of hippocampal membrane proteins under nondenaturating conditions
      showed NCAM to be present in protein complexes of different molecular weights at
      different developmental stages. We propose that NCAM is involved in the formation
      of developmentally regulated, noncovalent complexes with as yet unknown partner
      molecules that could be responsible for the masking of the D3-specific epitope.

PMID- 9272640
TI  - Comparison of the agonist binding site of homomeric, heteromeric, and chimeric
      GluR1(o) and GluR3(o) AMPA receptors.
AB  - A series of AMPA [(R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic
      acid] analogues were evaluated for activity at homomeric, heteromeric, and
      chimeric rat GluR1(o) and GluR3(o) receptors expressed in Xenopus oocytes, using
      the two-electrode voltage clamp technique. The formation of heteromeric receptor
      complexes was demonstrated by cross-immunoprecipitation of both subunits from
      solubilized oocyte membranes. The AMPA analogue ACPA [(R,S)-2-amino-3(3-carboxy-5
      methyl-4-isoxazolyl)propionic acid] was the most potent and selective agonist
      tested at GluR1(o) and GluR3(o), with a 10-fold selectivity for GluR3(o). ACPA
      showed an intermediate potency at both the GluR1(o) + 3(o) heteromeric complex as
      well as at the homomeric chimeric receptors. These experiments suggest that for
      receptor activation, agonist binding occurs between the interface of the GluR1
      and GluR3 subunits in the heteromeric channel complex, perhaps between the S1
      region of one subunit and the S2 region of another. Also, it seems that 1)
      electronegative group substitutions on the isoxazole ring of AMPA and 2)
      decreasing the pKa of the sub stituent at position 3 play a major role in
      determining the degree of receptor activation under steady-state conditions.
      Future studies will examine the effects of single amino acid mutations in these
      receptors, giving a more precise localization of the agonist binding site.

PMID- 9272641
TI  - Calmodulin-dependent cyclic nucleotide phosphodiesterase in adult and developing
      chick spinal cord.
AB  - We investigated the level and characteristics of "low Km" 3'-5' cyclic nucleotide
      phosphodiesterase (PDE) activity in adult and embryo chick spinal cord. The DEAE
      cellulose chromatography elution profile of Triton X-100 extracts showed a single
      peak of calmodulin-dependent cAMP/cGMP PDE activity. After two additional
      purification steps, this activity showed a five-fold activation by calmodulin (Ka
      = 1.5 nM) for cGMP hydrolysis, and a linear kinetic behaviour with a Km of 1.3
      microM. Conversely, the activity showed a biphasic behaviour for cAMP hydrolysis,
      with Km values of 3.1 and 18.5 microM. The enzyme showed a Stokes radius of 4.5
      nm. Western blot analysis of the purified enzyme revealed two immunoreactive
      bands with molecular mass of 59 and 65 kDa, respectively. Immunohistochemical
      staining showed motoneuron decoration both on cell soma and fibres. The
      developmental pattern of Ca2+-calmodulin-dependent PDE expression in spinal cord
      was also studied; the hydrolytic activity for both substrates has been found to
      increase constantly from E5 to post-hatching stages, when it appears 5.6-fold
      higher as compared to the early embryo levels. Furthermore, in cultured spinal
      cord neurons from E8 embryos, muscle extract has been shown to induce a two-fold
      increase of Ca2+-calmodulin-dependent cGMP activity. In conclusion, the studies
      reported here present three relevant findings: (1) the presence in adult and
      embryo chick spinal cord of PDE activities with characteristics similar to those
      of the mammalian PDE I enzyme; (2) its localization in the ventral horn
      motoneurons; (3) its regulated expression during embryogenesis that is possibly
      related to soluble epigenetic factors produced by the target cells.

PMID- 9272642
TI  - Effect of prior receptor antagonism on behavioral morbidity produced by combined
      fluid percussion injury and entorhinal cortical lesion.
AB  - We have used an animal model of traumatic brain injury (TBI) that incorporates
      both the neurotransmitter toxicity of fluid percussion TBI and deafferentation of
      bilateral entorhinal cortical (BEC) lesion to explore whether administration of
      muscarinic cholinergic or N-methyl-D-aspartate glutamatergic antagonists prior to
      injury ameliorates cognitive morbidity. Fifteen minutes prior to moderate central
      fluid percussion TBI, rats were given intraperitoneal injections of either
      scopolamine (1.0 mg/kg) or MK-801 (0.3 mg/kg) and 24 hr later underwent BEC
      lesion. Body weight was followed for 5 days postinjury, as was beam balance and
      beam walk performance to assure motor recovery prior to spatial memory testing.
      Each group was assessed for spatial memory deficits with the Morris water maze at
      short term (days 11-15) and long-term (60-64 days) postinjury intervals and then
      compared with untreated combined insult and sham-injured controls. Results showed
      that each drug significantly elevated body weight relative to untreated injured
      cases. Both scopolamine and MK-801 reduced beam balance deficits, whereas neither
      drug had a significant effect on beam walk deficits. Interestingly, short-term
      cognitive deficits assessed on days 11-15 were differentially affected by the two
      drugs: MK-801 pretreatment enhanced the recovery of spatial memory performance,
      whereas scopolamine pretreatment did not. Long-term (days 60-64) deficits in
      spatial memory were not altered by pretreatment with either drug. Our results
      suggest that, unlike fluid percussion TBI alone, behavioral impairment may
      require more select intervention when deafferentation is part of the head trauma
      pathology.

PMID- 9272643
TI  - Non-cholinergic, trophic action of recombinant acetylcholinesterase on mid-brain
      dopaminergic neurons.
AB  - Acetylcholinesterase (AChE) is secreted from various brain regions such as the
      substantia nigra, where levels of this molecule are disproportionately higher
      than those of choline acetyltransferase. It is thus possible that AChE may have
      alternative, non-cholinergic functions, one of which could be in development.
      Indeed, several recent studies have already demonstrated a neurotrophic action of
      AChE independent of hydrolysis of acetylcholine. In the developing nervous system
      the dominant forms of AChE differ from the tetramers (G4) that prevail in
      maturity, in that they are lower molecular weight monomers (G1) and dimers (G2).
      Therefore, the aims of this study were to explore the neurotrophic role of AChE
      by comparing the effects of mouse recombinant G1 and G4 AChE on the survival and
      development of mid-brain tyrosine hydroxylase immunoreactive neurons.
      Butyrylcholinesterase (BuChE), which also hydrolyses acetylcholine, and basic
      fibroblast growth factor (bFGF), an established trophic factor for midbrain
      neurons, were also tested. bFGF had no significant stimulatory effect: moreover,
      BuChE was also inefficacious, suggesting that the action of AChE was independent
      of its catalytic site. In contrast, mouse recombinant G1 and G4 AChE both
      increased the survival as well as the outgrowth of the cultured neurons. However,
      G1 AChE was more potent than G4 AChE suggesting that developmental forms of AChE
      exist. The implications of this finding for physiological and pathological
      functioning of the nervous system are discussed.

PMID- 9272644
TI  - Quantification of the effects of astrocytes on oligodendroglial morphology.
AB  - Oligodendrocytes in neonatal rat forebrain cultures grow either in isolation of
      other cells or upon astrocytes. Populations of both types of oligodendrocytes
      were used to quantify the effects of astrocytes on oligodendroglial morphology.
      Changes in oligodendroglial size and shape were determined by measurement of
      total process length, cell area, growth area, and fractal dimension. The
      directionality of process growth, quantified by measurement of the axes of
      growth, was also compared. Isolated oligodendrocytes exhibited greater total
      process length, greater cellular area, larger growth area, and a more complex
      boundary than oligodendrocytes growing upon astrocytes. Analysis of the axes of
      cellular growth revealed that the processes of isolated oligodendrocytes
      exhibited radial symmetry, whereas the processes of oligodendrocytes growing upon
      astrocytes were limited to an area demarcated by the astrocytic processes. These
      data suggest that, in neuron-free culture, the growth of oligodendroglial
      processes is modified by underlying astrocytic processes.

PMID- 9272645
TI  - beta-amyloid protein enhances macrophage production of oxygen free radicals and
      glutamate.
AB  - Cells of the monocyte phagocytic system can generate superoxide and glutamate
      anions, both of which are neurotoxic at high levels. We used rat peritoneal
      macrophages as a model system to test the effects of various stimulants on the
      production of these molecules. Glutamate production by such cells was enhanced,
      in a concentration-dependent manner, by treatment with serum-opsonized zymosan
      (OZ), lipopolysaccharide (LPS), phorbol myristate acetate (PMA), and beta-amyloid
      peptide Abeta (1-40); but not by treatment with the reverse Abeta (40-1) or the
      Abeta (25-35) subfragment. Superoxide anion production by the cells was
      stimulated by OZ, PMA, Abeta (1-40), and Abeta (25-35). Moreover, Abeta and its
      subfragment, when used as priming agents, also enhanced the stimulatory effect of
      PMA. However, they did not act as priming agents for OZ, suggesting a competition
      for receptors or intracellular signaling pathways linked to those receptors.
      Inflammatory mediators, including Abeta, could place glutamate-sensitive neurons
      at risk by enhancing glutamate and oxygen free radical production by monocyte
      derived cells. Such mechanisms could contribute to the pathogenesis of
      neurodegenerative disorders, including Alzheimer's disease.

PMID- 9272647
TI  - Proliferation of ramified microglia on an astrocyte monolayer: characterization
      of stimulatory and inhibitory cytokines.
AB  - Proliferation of ramified microglia is a common phenomenon in brain pathology,
      but little is known about how this is regulated. In the current study, we
      examined the effect of different cytokines on the proliferation of ramified
      microglia in vitro using a combination of autoradiography for [3H]-thymidine and
      immunocytochemical techniques. Ramified microglia were obtained using a 10-day co
      culture on top of a confluent astrocyte monolayer. Addition of macrophage colony
      stimulating factor (MCSF), granulocyte-macrophage colony-stimulating factor
      (GMCSF), and interleukin-3 (IL3), stimulated the proliferation of ramified
      microglia, with a 7.2-fold, 3.5-fold, and 1.5-fold increase, respectively. Of all
      the other cytokines tested (IL1, IL2, IL4, IL6, IL10, interferon-gamma
      (IFNgamma), leukemia inhibitory factor (LIF), and tumor necrosis factor-alpha
      (TNFalpha) only IL1 strongly enhanced proliferation. However, this effect of IL1
      was indirect and could be neutralized by antibodies against MCSF and GMCSF. IL2,
      IL4, IL10, TNFalpha, and IFNgamma inhibited microglial proliferation. The great
      number of inhibitory cytokines could point to the importance of containing
      microglial proliferation in the central nervous system.

PMID- 9272646
TI  - cAMP-dependent protein kinase A is required for Schwann cell growth: interactions
      between the cAMP and neuregulin/tyrosine kinase pathways.
AB  - Schwann cell proliferation is stimulated by contact with neurons or exposure to
      growth factor ligands for tyrosine kinase receptors, effects of which are
      potentiated by cAMP. Here we show that treatment of rat Schwann cells with
      recombinant human glial growth factor 2 (rhGGF2), but not with other mitogenic
      factors, transiently increases intracellular cyclic AMP (cAMP), with maximal
      elevation at the G0/G1 boundary. The cAMP-dependent protein kinase (PKA)
      inhibitor H-89 strongly antagonized GGF- and neuron-induced Schwann cell
      proliferation, with maximum inhibition observed at G0/G1. H-89 also inhibited
      Schwann cell proliferation induced by growth factors that did not increase
      intracellular cAMP. Stimulation of Schwann cells with rhGGF2 resulted in 70-fold
      activation of MAP kinase; forskolin treatment resulted in a 50% decrease in MAP
      kinase activity but did not alter Raf-1 phosphorylation on Ser-43. These results
      demonstrate that the MAP kinase cascade represents an intersection between
      receptor tyrosine kinase and cAMP signaling pathways in Schwann cells and that
      PKA plays a critical role in Schwann cell cycle progression.

PMID- 9272649
TI  - Development of degenerative muscle weakness by chronic administration of
      beta,beta'-iminodipropionitrile in the drinking water to rats: a model for
      motorneuropathy.
AB  - Progressive muscle weakness accompanied by progressive muscle atrophy was
      investigated in rats administered beta,beta'-iminodipropionitrile (IDPN)
      chronically in the drinking water. Spontaneous running wheel activity declined
      slowly and reached a constant low level before postural muscle weakness was
      apparent. The rats being offered IDPN in the drinking water showed definite
      postural muscle weakness about 25 weeks after first being given IDPN, and muscle
      strength declined gradually throughout the remainder of the experiment (to 66
      weeks). Flaccid paralysis became apparent in the hind limbs in the later stages
      of the experiment. Neurogenic muscle atrophy, measured by group atrophy of the
      muscle fibers, also progressed slowly, almost in parallel with the loss of muscle
      strength. At the end of the experiment, muscle weight of the gastrocnemius had
      decreased to about 20% that of control [F(2, 12) = 40.4, p < 0.05]. Plasma
      creatinine in the rats given IDPN in the drinking water for 66 weeks was
      significantly elevated over that of controls [F(2, 12) = 20.1, p < 0.05]. On the
      other hand, in rats given IDPN intraperitoneally, postural muscle weakness and
      muscle atrophy were less apparent, and plasma creatinine was normal. However, in
      these animals, abnormal behaviors, such as hyperexcitement, circling, and choreic
      movement (ECC syndrome), were apparent. These results suggest that the present
      model, which administers IDPN chronically in the drinking water ad lib and does
      not show involuntary movements and ECC syndrome, is of potential importance for
      investigation of chronic diseases of progressive muscle weakness with progressive
      muscle atrophy, and for assessing the efficacy of drugs and therapies for
      treating chronic neuromuscular diseases.

PMID- 9272650
TI  - Effect of dietary supplementation with branched-chain amino acids on spontaneous
      motor activity and muscle function in beta,beta'-iminodipropionitrile-treated
      rats: a model for motorneuropathy.
AB  - Beta,beta'-iminodipropionitrile (IDPN)-induced muscle weakness in rats is a model
      for motorneuropathy diseases. The effects of oral administration of branched
      chain amino acids on the progression of muscle weakness and muscle atrophy
      induced by the administration of IDPN in the drinking water, were investigated in
      this study. The spontaneous motor activity of the animals, as measured with a
      running wheel, slowly declined after IDPN administration, reaching a steady and
      low level at approximately week 15. Progressive muscle weakness and muscle
      atrophy were observed beginning at approximately 15 weeks after the initiation of
      administration of IDPN. Administration of branched-chain amino acids (BCAA) as a
      dietary supplement did not improve the lowered spontaneous motor activity seen in
      IDPN animals, but it did significantly improve measures of postural weakness and
      muscle strength [range of F values (2, 24) = 4.1-9.5, p < 0.05]. Plasma
      creatinine of the IDPN-treated rats was markedly elevated, and BCAA
      administration also significantly suppressed this elevation [F(2, 24) = 41.2, p <
      0.05]. Moreover, although BCAA in plasma were elevated in the rats administered
      BCAA [range of F values (2, 21) = 25.7-29.7, p < 0.05], skeletal muscle showed no
      differences (at the p < 0.05 level) in the amounts of BCAA, whether or not BCAA
      were administered. These data suggest that the BCAA taken up in the skeletal
      muscle were utilized in the muscle of motorneuropathic rats and improved muscle
      function, such as energy metabolism, and that the BCAA treatment is one important
      therapeutic approach for retarding the progression of muscle weakness seen in
      certain neuromuscular disorders.

PMID- 9272648
TI  - Plasma catecholamine and corticosterone levels during manual restraint in chicks
      from a high and low feather pecking line of laying hens.
AB  - Neurosympathetic and adrenal responsivity to manual restraint was studied in two
      White Leghorn chicken lines which differ in their tendency to feather peck. Blood
      samples were taken from freely moving cannulated birds during resting conditions
      and during manual restraint (placing the bird on its side for 8 min) to determine
      plasma noradrenaline. adrenaline and corticosterone. Plasma corticosterone levels
      in low feather peckers (LFP) were significantly higher during resting conditions
      and restraint as compared to the high feather peckers (HFP). In response to
      manual restraint the HFP hens showed a significantly larger plasma noradrenaline
      response than LFP hens. No difference in plasma adrenaline levels was observed
      under resting conditions or during manual restraint.

PMID- 9272651
TI  - Stress-induced hyperthermia in singly housed mice.
AB  - The stress-induced hyperthermia (SIH) paradigm in group-housed mice allows
      screening of putative anxiolytic drugs. The group-housed SIH was adapted to
      singly housed animals in order to drastically reduce the number of animals used.
      The effect of various stressors on rectal temperature was measured in order to
      find a simple and reliable test procedure. Repeated, but not single disturbance
      of animals resulted in a strong hyperthermia (deltaT) within 10 min. Similar
      hyperthermic responses were obtained after immobilization for 1 min or rectal
      temperature measurement itself. Neither a 120 dB acoustic stimulus, nor repeated
      1 mA footshocks led to a temperature change, but 2 mA electric footshocks led to
      hyperthermia. The final test paradigm chosen involved repeated temperature
      measurement at a 10 min interval, thus providing both information on basal
      temperature and deltaT in each animal within a short time frame. Repeated
      temperature measurements at 10 min intervals revealed a maximum hyperthermia
      after approximately 30 min, but up to 70% of the hyperthermia is already present
      10 min after the first measurement. Repeated use of animals at successive daily
      or weekly intervals resulted in a gradual increase of both the basal temperature
      and the temperature 10 min later. At short inter-test intervals (one day) deltaT
      also decreased, whereas weekly intervals did not affect the amplitude of deltaT.
      Prior injection of the animals resulted in modest hyperthermia, that returned to
      baseline after 60 min. The anxiolytics diazepam and 5-HT1A receptor agonist
      flesinoxan dose-dependently suppressed SIH. The antidepressant amitriptyline
      lowered temperature levels but did not affect deltaT. The SIH model in singly
      housed mice appears a fast and reproducible screening test for anxiolytic
      activity. Compared to the group-housed version, the singly-housed SIH enabled a
      drastic reduction in the number of animals used.

PMID- 9272652
TI  - Blood glucose and subjective energy following cognitive demand.
AB  - Previous studies have found a small association between the level of blood
      glucose and subjective reports of energy in those sitting quietly. Given reports
      that both memory and attention are influenced by the level of blood glucose it
      was hypothesised that under conditions of cognitive demand there would be a
      stronger association between mood and blood glucose levels. In three studies,
      with three cognitive tasks, the Stroop Task, Rapid Information Processing Task,
      and a difficult test of hand-eye coordination, falling blood glucose was
      associated with feeling less energetic.

PMID- 9272653
TI  - Schedule induction conditions not only exaggerate intake but also enhance drug
      solution choice.
AB  - In previous research, rats exposed to daily, 3 h sessions of schedule-induced
      polydipsia (SIP) self-administered high doses of cocaine orally. However, a
      strong and durable preference for cocaine solution to water requires training in
      addition to mere oral self-administration exposure. If cocaine is dissolved in a
      preferred vehicle solution, and the vehicle is subsequently faded to water, then
      a strong preference for cocaine remains. A similar preference can be instituted
      for lidocaine solution. Such preferences may develop because the gustatory
      property of a drug becomes associated with the preferred vehicle and remains to
      function as a durable conditioned reinforcer after vehicle fading. To determine
      if drug preference is solely a function of this posited conditioning mechanism,
      or whether it also depends upon the SIP condition, rats were exposed to daily, 3
      h sessions of single-ration feeding, rather than the SIP condition. A preferred
      vehicle (glucose/saccharin solution) was slowly faded from a 0.19 mg/ml lidocaine
      solution, which was presented concurrently with a choice for water. Although a
      preference for lidocaine solution to water could be generated, it occurred for
      only 5 out of 9 rats, and the preference was relatively unstable. By contrast, in
      two previous studies using SIP, 26 out of 27 rats maintained a preference for
      lidocaine solution. Thus, SIP not only exaggerates the amount of drug solution
      ingested but also contributes to the fixation of the associative drug solution
      choice.

PMID- 9272654
TI  - Plasma cortisol levels of dogs at a county animal shelter.
AB  - Plasmacortisol levels were examined to assess the stress of dogs in a county
      animal shelter. Groups of dogs confined in the shelter for their 1st, 2nd, or 3rd
      day had higher cortisol levels than did a group maintained in the shelter for
      more than 9 days. Dogs in the shelter for an intermediate period (Day 4-9) had
      intermediate levels of cortisol. The cortisol concentrations of dogs during their
      first day in the shelter were greater than either those of the same dogs on Day
      4/5 in the shelter or those of a group of pet dogs sampled in their own homes.
      There was no overall effect of 20 min of social interaction with a human (e.g.,
      petting) on the plasma cortisol levels of dogs in the shelter on Day 1-3.
      However, the gender of the petter did affect cortisol levels. Those dogs
      interacting with a female had lower cortisol concentrations at the end of the
      session than did dogs interacting with a male. The results suggest that
      confinement in a public animal shelter produces a prolonged activation of the
      hypothalamic-pituitary-adrenal axis. Further, it appears that some subtle aspect
      of interaction with a human may be capable of moderating this response. Possible
      implications for the welfare of confined dogs, and for the development of
      behavior problems in dogs obtained from shelters, are discussed.

PMID- 9272655
TI  - Citrate ions enhance behavioral and cellular responses to taste stimuli.
AB  - Behavioral and electrophysiological experiments have been performed on male
      Sprague-Dawley rats to evaluate the effectiveness of citrate ions as taste
      enhancers. In two- and four-day two bottle preference tests (vs. water), citrate
      (1-25 mM) significantly enhanced preference for sweet compounds and the amino
      acid glycine over control (non-citrate containing) solutions. Under conditions in
      which animals were "forced" to choose between test solutions with or without
      citrate, saccharin, sucrose, glycine and NaCl solutions containing citrate were
      significantly preferred over controls. In addition to its effects on sweet,
      glycine and NaCl taste, short term preference tests following water deprivation
      revealed that citrate modulated acid taste preference, as well. Bitter taste
      preference remained insensitive to citrate in all behavioral assays. As a
      preliminary attempt to elucidate the target of citrate's actions,
      electrophysiological responses of isolated fungiform taste receptor cells (TRCs)
      to saccharin and glycine were recorded using patch clamp techniques. Saccharin
      (20 mM) and glycine (50 mM) elicited action potentials from TRCs in current clamp
      mode. Addition of citrate caused a significant increase in number of action
      potentials generated per 30 s stimulation. Citrate caused a slight but
      significant depolarization from resting potentials in most TRCs, independent of
      tastant effects. Taken together, these results suggest that citrate acts at the
      receptor cell level to enhance only those responses to tastants which depolarize
      TRCs (i.e. sweet, salt, glycine, acid) while leaving unaffected those which do
      not depolarize TRCs (bitter).

PMID- 9272656
TI  - Chronic exposure to the opioid antagonist naltrexone during pregnancy: maternal
      and offspring effects.
AB  - The role of endogenous opioids in pregnancy and parturition, and the influence
      exerted on prenatal and postnatal features of the offspring, were studied in
      rats. Females received daily injections of 50 mg/kg naltrexone (NTX), a dosage
      found to block opioids from interacting with opioid receptors for 24 h,
      throughout pregnancy. No effects on the length of gestation, course of pregnancy,
      litter size, or the viability of the mother or offspring were noted. The body
      weights, crown-rump lengths, and wet and dry weights of the brain, heart, kidney,
      liver, and skeletal muscle (triceps surae) in neonates delivered by NTX-treated
      rats were substantially elevated compared to newborn animals of saline-injected
      mothers. Offspring exposed to NTX during prenatal life were larger in body weight
      and length, and organ wet and dry weights on postnatal days 10 and 21. By weaning
      (day 21 ), body weights of NTX-exposed rats were 36% greater than controls, and
      increases were observed in the wet weights of brain (18%), heart (42%), kidney
      (38%), lungs (22%), liver (44%), and triceps surae (246%). These data lead us to
      hypothesize that native opioids are important growth-inhibiting, tonically active
      regulators of prenatal ontogeny, and that events occurring in prenatal life are
      determinants to postnatal outcome insofar as somatic development.

PMID- 9272657
TI  - Isolated-brain parallels to simple types of learning and memory in Tritonia.
AB  - Physiological studies of learning and memory often require reduced nervous system
      preparations that can be trained by stimulation of neural pathways in a manner
      that mimics behavioral training. In the isolated brain preparation of the seaslug
      Tritonia, fictive swimming can be activated with a few electrical pulses applied
      to the cut end of a nerve, and learning experiments can be simulated with
      combinations of nerve stimuli. Repeated application of a nerve stimulus produced
      changes in fictive swimming that resembled habituation and iterative enhancement
      of multiple components of the swimming behavior. Many repetitions of the nerve
      stimulus led to fictive swimming failure. Stimulation of another nerve then
      restored the ability of the original nerve to activate fictive swimming, thus
      reproducing dishabituation results. Sensitization of threshold and latency were
      also simulated. Parallels between the behavior and the isolated brain suggest
      that the neuronal modifications underlying simple types of learning can be
      induced by nerve stimulation. The activity pattern of interneuron C2 in these
      experiments suggests that increased C2 synaptic efficacy may underlie
      sensitization of swimming latency.

PMID- 9272658
TI  - Adrenalectomy lowers the body weight set-point in rats.
AB  - In order to evaluate the impact of a complete depletion of glucocorticoids on
      rats' body weight set-point, rats were adrenalectomized, and their set-points
      were estimated before, and after surgery. Body weight set-points were obtained
      from a quantitative behavioral method based on the rats' food-hoarding response
      to weight deficit. In addition, body fat contents were measured in vivo using a
      total body electrical conductivity analyzer (TOBEC). The hoarding of food showed
      that adrenalectomized rats had significantly lower body weight set-points than
      the sham-operated controls (337 +/- 11 g vs. 385 +/- 8 g) and were also
      significantly lighter. TOBEC measurements showed that the sham-operated control
      rats had a higher body fat content than the adrenalectomized rats ( 16.7 +/- 1.1%
      vs. 10.2 +/- 1.2%). The present study demonstrates that adrenalectomy lowers the
      body weight set-point in rats, suggesting that the concentrations of
      glucocorticoid hormones, and in turn, the hypothalamic corticotrophin releasing
      hormone (CRH) participates in the adjustment of the body weight set-point.

PMID- 9272659
TI  - Meal patterns prior to and following liver transplantation in rats.
AB  - Afferent nerves of the liver have been suggested to have a major influence on
      feeding behavior. Nevertheless, total liver denervations (TLD) in rats, that were
      verified by histofluorescence technique, did not change short or long term meal
      patterns. However, these studies have been criticized that the TLD procedures may
      have missed some liver innervation. In the present study meal patterns were
      conducted prior to and following liver transplantation in rats using a transplant
      procedure with arterialization. The transplanted rats recovered their pre
      operative body weight in 7.5 +/- 0.6 days and meal pattern analysis was conducted
      two days later. In comparison with pre-surgery there was no differences in 24 h
      food intake (gms); dark phase: intake (gms), meal size (gms), meal duration
      (min), inter-meal interval (min), and frequency; and light phase: intake (gms),
      meal size (gms), meal duration (min), inter-meal interval (min), and frequency.
      These data, like earlier work in TLD rats showing that the animals consumed
      normal meals (when offered a variety of diets), starting with the first meal post
      surgery, question the importance of liver afferents in the control of feeding
      behavior.

PMID- 9272660
TI  - Naloxone microinjected into the arcuate nucleus has differential effects on
      ventilation in male and female rats.
AB  - The arcuate nucleus of the hypothalamus, a highly sexually dimorphic brain
      region, has been called the bed nucleus for endogenous opioids. The potential
      contribution of opioids in this nucleus to modulate control of ventilation in
      male and female rats has not been investigated. The purpose of the present study
      is to determine the effect of microinjecting naloxone, an opioid receptor
      antagonist, into the arcuate nucleus of awake male and female rats on
      ventilation, oxygen consumption, heart rate, and blood pressure. Results of this
      study demonstrate that naloxone at doses of 1.5 and 3.0 nmol relative to vehicle
      caused a depression of ventilation due to a decrease of both frequency of
      breathing and tidal volume in male rats and a decreased response to a hypercapnic
      challenge in female rats. Although there were gender differences noted in oxygen
      consumption, heart rate, blood pressure, and ventilatory response to a hypoxic
      challenge, only oxygen consumption was significantly affected by naloxone.
      Potential mechanisms whereby naloxone may act to depressing ventilation are
      discussed.

PMID- 9272661
TI  - Infusion of CCK-A receptor mRNA antisense oligodeoxynucleotides inhibits lordosis
      behavior.
AB  - Cholecystokinin (CCK) acting on discrete receptors in the limbic-hypothalamic
      circuit modulates lordosis behavior. Neurons in the medial preoptic nucleus (MPN)
      express CCK-A subtype receptor mRNA, and site-specific infusions of CCK
      facilitate lordosis, suggesting that CCK-A receptor activation positively
      modulates lordosis. In the present study, we demonstrated CCK binding in the
      central portion of the MPN (MPNc) and the disruption of lordosis behavior by
      reducing the expression of CCK-A receptors in this nucleus. Antisense
      oligodeoxynucleotides (ODN) specific for CCK-A receptor mRNA were infused into
      the MPN of ovariectomized female rats. The expression of estrogen-induced
      lordosis behavior was blocked in animals receiving infusions of antisense ODN
      into the MPN (LQ = 10.0 +/- 1.0) compared to animals receiving infusions of
      nonsense ODN (containing the same nucleotide bases in a random order; LQ = 92.5
      +/- 7.5). In vitro, AR42J pancreatic acinar carcinoma cells treated with
      antisense ODN had lower levels of CCK-A and CCK-B subtype receptor binding than
      nonsense ODN treated cells. In vivo, however, infusions of CCK-A mRNA antisense
      ODN did not alter CCK-B receptor binding levels. These results suggest that CCK,
      acting via CCK-A receptors in the MPNc, is critical for the display of lordosis
      behavior.

PMID- 9272662
TI  - Devazepide attenuates dl-fenfluramine-induced suppression of gastric emptying but
      not food intake in the 17 h food-deprived rat.
AB  - Recently a number of studies have provided evidence which suggests that CCK and 5
      HT interact in the control of food intake. The present experiments further
      examine this mechanism and the possibility that CCK and 5-HT interact in the
      control of gastric emptying. The selective CCK-A receptor antagonist, devazepide,
      (0.03-3.0 mg/kg) administered alone had no intrinsic effect on gastric emptying.
      Devazepide (0.1 and 0.3 mg/kg) blocked dl-fenfluramine-induced (3.0 mg/kg)
      suppression of gastric emptying. However, devazepide (0.03-3.0 mg/kg) failed to
      attenuate the anorectic effect of the same dose of dl-fenfluramine. These results
      suggest that under the present experimental conditions CCK and 5-HT interact in
      the regulation of gastric emptying but not food intake. Thus the interaction
      between CCK and 5-HT in the regulation of gastric emptying appears not to affect
      the control of ingestive behaviour.

PMID- 9272663
TI  - Unpredictable deprivation of water increases the probability of torpor in the
      Syrian hamster.
AB  - The effect of unpredictable water deprivation on hibernation was investigated in
      the Syrian hamster under natural photoperiod and temperature. Based on our
      previous findings, we hypothesized that 1) deprivation of water caused testicular
      regression, 2) the magnitude of regression depended on unpredictability of water
      deprivation, 3) unpredictable deprivation of water on 50% of the days of the
      experimental period causes more testicular regression for animals than regular
      deprivation every other day, even if the total lengths were the same for the two
      treatments, and thus, 4) unpredictable deprivation of water induces hibernation
      more readily than regular deprivation or no deprivation. The results showed that
      the animals with the random and unpredictable deprivation a) started hibernation
      earlier, b) had a higher chance of being in torpor at the end of hibernation
      season, c) spent more time in torpor during hibernation than those animals which
      were deprived of water on a regular basis or the control, non-deprived animals.
      These findings supported our working hypothesis.

PMID- 9272664
TI  - Acoustic startle-evoked potentials in the rat amygdala: effect of kindling.
AB  - The electroencephalogram (EEG) of the basolateral nucleus of the amygdala (BLA)
      was recorded during presentation of acoustic stimuli (70-110 dB SPL) in rats. EEG
      recordings were performed by chronically implanted bipolar electrodes in the BLA.
      The auditory evoked response consisted of a broad negative wave followed by a
      slow positive wave. A characteristic pattern of 1 to 3 negative peaks with a
      latency of about 12 ms and an increased amplitude of the slow positive wave at
      about 30 ms was observed when an acoustic startle response (ASR) occurred. These
      findings suggest that the BLA is involved in the processing of adverse auditory
      stimuli. These ASR-correlated potentials in the BLA were used to characterize
      changes of the physiological state of the amygdala that occur after chronic
      epileptogenesis. To achieve this aim, the rats were subsequently partially or
      fully kindled by daily electrical stimulation via the recording electrode. The
      negative peak was depressed in the partially kindled rats, but not in fully
      kindled rats. These changes in the characteristic EEG pattern of the BLA during
      the ASR indicate alteration of the physiological response of the amygdala after
      limbic epileptogenesis.

PMID- 9272665
TI  - Weight, protein, fat, and timing of preloads affect food intake.
AB  - Two foods, one rich in protein (HP) and one rich in fat (HF), were employed to
      evaluate the effect of macronutrients on food intake and to underline the
      differences that occurred when the foods were served as uniform meal, as first
      course of a varied meal, and as a snack 2 h before a varied meal. Our results
      showed that HP food always exerted a higher effect on both intrameal satiation
      and postingestive satiety than HF food. When a uniform meal was consumed,
      satiation for the specific food was reached before fullness; in this condition,
      sensory characteristics of foods played an important role in controlling food
      intake and made the uniform meal more satiating than the varied one. The
      consumption of a snack far from a meal did not contribute to satiety;
      consequently, gastric filling seems to be an important factor determining the
      amount consumed in a varied meal.

PMID- 9272666
TI  - Differential effects of D1 and D2 dopamine-receptor agonists and antagonists on
      appetitive and consummatory aspects of male sexual behavior in Japanese quail.
AB  - Pharmacological studies in Japanese quail based on behavioral tests with a
      variety of dopaminergic compounds suggest that the activation of D2 dopamine
      receptors inhibits, and the activation of D1 dopamine receptors enhances,
      appetitive and consummatory components of male sexual behavior. This hypothesis
      was tested by studying the behavioral effects of specific D1 and D2 dopaminergic
      receptor agonists and antagonists in castrated male Japanese quail chronically
      treated with exogenous testosterone (subcutaneous Silastic implants). The effects
      of 5 compounds were tested: 1 D1 (SKF38393) and 2 D2 (PPHT and quinpirole)
      agonists, and 1 D1 (SCH23390) and 1 D2 (Spiperone) antagonist. All compounds were
      tested at a low and a high dose (0.1 and 1 mg/kg, respectively, for all drugs,
      except spiperone where the doses were 2 and 10 mg/kg). A consistent effect of all
      drugs on consummatory sexual behavior was observed: it was stimulated by the D1
      agonist and the D2 antagonist, but inhibited by the D1 antagonist and the D2
      agonists. Far fewer effects of the treatments were detected on the measures of
      appetitive behavior. Measures of appetitive behavior were decreased by the 2 D2
      agonists, but not affected by the other treatments. These data suggest that male
      copulatory behavior in quail is stimulated by dopamine acting on D1 receptors,
      but inhibited by activation of the D2 receptor subtype. The partial dissociation
      observed between the effects of the same treatments on appetitive and
      consummatory aspects of sexual behavior also suggests that these 2 behavioral
      systems may be controlled by the action of dopamine on different neuronal
      systems.

PMID- 9272668
TI  - A neuronal transition probability model for the evolution of power in the sigma
      and delta frequency bands of sleep EEG.
AB  - Although the time-courses of power in the delta and sigma frequency bands over
      the NREM episode in the human sleep EEG have been studied for several years, and
      their detailed forms have been well measured, no mathematical model has yet been
      formulated to account for the relation between them. The model presented here
      attempts to explain the form and relative timing of these curves by a
      consideration of the behavior of the thalamocortical neuronal populations that
      are believed to play a part in their generation. The model applies the
      mathematics of the cascade radioactive decay process, adapted to a finite
      population of thalamocortical neurons oscillating initially in the beta mode. At
      the beginning of the NREM episode, each neuron of this population is assumed to
      acquire a constant probability of transitionning to the sigma oscillation mode
      and, at the same time, each neuron of the newly created sigma population is
      assumed to acquire a constant probability of transitionning to the delta
      oscillation mode. This simple model is sufficient to explain the main
      characteristics of the first half of the time-courses of the sigma and delta
      powers: the initial positive correlation as they increase together, followed by
      the sigma peak and the subsequent negative correlation. At the end of this first
      phase, the model initiates an identical, but reverse, process that reproduces the
      observed delta maximum and sigma plateau, followed by the concomitant fall of
      both sigma and delta power. The time-course of the beta power and the overall
      negative correlation between beta and delta are also reproduced as integral
      consequences of the model.

PMID- 9272667
TI  - Pain-related behaviour following sodium urate arthritis is expressed in
      decerebrate chickens.
AB  - The role of the telencephalon in pain-related behaviour in arthritis was
      investigated by measuring pain-coping behaviour (one-legged standing, lameness,
      sitting) of birds following intra-articular injection of sodium urate crystals.
      Ten sham-operated and 10 decerebrate birds were injected with sodium urate into
      the left ankle joint 4 days after surgery, and their behaviour recorded during a
      3-h period. Both groups of birds showed pain-coping behaviour, and there was no
      significant difference between the 2 groups of birds. These results suggest that
      the behaviours associated with tonic arthritic pain are organised in the
      brainstem.

PMID- 9272669
TI  - Reduction in buoyancy alters parameters of motility in E9 chick embryos.
AB  - Over the course of embryonic development, chick embryos express 3 different types
      of motility (I, II, III). Although neural pattern generators appear to control
      embryonic motility, the mechanisms responsible for the sequential emergence
      and/or transformations in these behaviors are not known. Given the early presence
      of functional sensory connections and substantial changes in movement dynamics
      associated with body growth in the fixed volume of an egg, it was hypothesized
      that changes in environmental constraints might contribute to shaping the
      transformations in motility. In this study, we tested the hypothesis that changes
      in buoyancy can alter parameters of motility in ovo at embryonic Day 9 (E9).
      Results demonstrate that attributes of Type I motility can be altered by a
      reduction in buoyancy. The possible contributions of the environment and
      experience to transformations in embryonic motor behavior are discussed.

PMID- 9272670
TI  - Effects of cocaine-induced seizures during pregnancy in the rabbit.
AB  - The effects of chronic administration of cocaine to pregnant rabbits on maternal
      seizures and on pregnancy outcome were studied. Cocaine (2, 3 or 4
      mg/kg/injection) or saline was administered, I.V., twice daily, from gestation
      Day 8 (G8) to G29. There were no significant differences in maternal weight gain
      or pregnancy outcome between saline control animals and animals given a cocaine
      dose of 2, 3 or 4 mg/kg/injection. Generalized tonic-clonic seizures (GTCSs) were
      occasionally elicited by the highest dose (4 mg/kg). There were significant
      individual differences in vulnerability to cocaine-elicited GTCSs in animals
      given 4 mg/kg/injection. Of this group, 18% were classified as having high
      vulnerability to seizures, and they experienced a range from 3 to 27 GTCSs.
      Postnatal mortality of their offspring was significantly increased. The incidence
      and temporal patterns of GTCSs elicited by chronic, I.V. cocaine in rabbits, at
      the doses used, are similar to those reported in human cocaine use. These GTCSs
      may involve different mechanisms from seizures elicited in other animal studies,
      in which high doses of cocaine are administered I.P. or S.C. Nevertheless, in our
      animal model, the GTCSs elicited by prenatal cocaine exposure had no detectable
      effects on pregnancy outcome (except in the highly vulnerable subgroup).

PMID- 9272671
TI  - Effects of toxin magnitude on taste aversion and taste-potentiated aversion to
      visual cues in chicks (Gallus domesticus).
AB  - Chicks (n = 208) received CS solutions of red water, red 2.0% vinegar, clear
      water, or clear 2.0% vinegar, followed by an I.P. injection of 0.4 M lithium
      chloride at 0.2% or 0.5% body weight, and then received 2 test trials with red
      water or clear 2.0% vinegar. In testing with red water, measures of latency to
      start drinking, latency to make 9 more drinks after the first, and amount drunk
      provided reliable evidence of potentiated aversion to visual cues with a greater
      magnitude of potentiation shown following the 0.2% injection than the 0.5%
      injection. In testing with clear vinegar, the "9-drink" latency measure and
      amount drunk yielded reliable evidence of taste aversion, with greater aversion
      shown following the 0.5% injection than the 0.2% injection. Findings are
      discussed in terms of associative and taste primacy views of potentiation
      effects.

PMID- 9272672
TI  - Effects of taste preexposure on aversion training to visual cues in chicks
      (Gallus domesticus).
AB  - Two experiments investigated whether or not prior taste experience influenced the
      utility of telereceptive cues in controlling ingestive behavior. Specifically,
      these experiments studied the influence of preexposure to taste cues on the
      effects of aversion training to visual telereceptive cues. In Experiment 1,
      chicks (n = 52) received preexposure to either clear 2.0% vinegar, clear water,
      or red-colored water or no preexposure, followed by a pairing of red-colored
      water and an injection of lithium chloride (LI). Testing with red water showed
      that preexposure to vinegar produced a reliably slower latency to start drinking
      than did preexposure to clear water or no preexposure which, in turn, differed
      reliably from the effects of preexposure to red water. The vinegar-preexposed
      group drank reliably less red water than did the red water-preexposed group.
      Experiment 2 investigated whether or not similarity between preexposure and
      aversion training contexts influenced the effects of taste preexposure on the
      results of visual aversion training. Chicks (n = 60) received pretraining
      exposure to clear 2.0% vinegar, clear water, or no preexposure in a context that
      was similar or different from that of aversion training, which occurred with red
      water. Testing with red water showed that preexposure to vinegar in a context
      similar to that of aversion training yielded reliably slower latency to start
      drinking than did either preexposure to clear water or no preexposure or
      preexposure in a context different from that of training. Results of the intake
      measure were consistent with the latency data, but were not reliable.

PMID- 9272673
TI  - Differential gender response produced by meal and ad lib feedings of a high-fat
      diet in Osborne-Mendel rats.
AB  - We investigated if there were gender differences in metabolic consequences
      produced by meal feeding of a high-fat (HF) diet in male and female Osborne
      Mendel rats. An HF diet was fed either ad lib (AL) or in 1 meal (MF) during the
      last 3 h of the dark cycle for 4 weeks (lights off from 2400 h to 1200 h). All
      rats were sacrificed at 1 of 3 time-points: prior to MF rats receiving their food
      at 0900 h, after food was taken from MF groups at 1200 h or 1500 h. Food intake,
      body weight, body fat weight, retroperitoneal adipose tissue lipoprotein lipase
      activity, plasma cholesterol, or HDL-cholesterol levels did not differ between MF
      and AL-fed groups, but were higher in male than in female rats. There were no
      differences between the male and female groups in plasma levels of insulin and
      glucose or systolic blood pressures. Plasma triglyceride levels at 1200 h were
      significantly different between MF and AL Groups within either gender, but this
      was not observed at 0900 h or 1500 h. Body weights were correlated with internal
      fat weights and plasma cholesterol levels in both males (r = 0.57, p < 0.05) and
      females (r = 0.59, p < 0.05). Hence, it is the amount of HF diet ingested, rather
      than the pattern of meal feeding, that was the most significant factor related to
      gender differences in weight gain, increases in fat mass, and metabolic
      differences.

PMID- 9272674
TI  - The circadian rhythm of salivary cortisol in growing pigs: effects of age,
      gender, and stress.
AB  - This experiment was designed to examine circadian rhythmicity of cortisol in
      saliva of growing pigs, in relation to age, gender, and (time of) stressor
      application. Additionally, the acute cortisol response to a stressor was studied.
      Five groups, each consisting of 3 barrows and 3 gilts, were involved in the
      experiment. In a Control Group, saliva samples were taken at 1-h intervals at 12,
      16, 20, and 24 weeks of age. Within 1 week, rhythmicity of cortisol was assessed
      during two 24-h spans (Monday and Friday). Rhythm characteristics were evaluated
      by cosinor analysis, describing the rhythm by several parameters. In 2 groups at
      12 weeks and 2 other groups at 20 weeks of age, a stressor was applied (4 h of
      isolation) on Thursday morning or evening. Again, rhythmicity was assessed on
      Monday and Friday by sampling at 2-h intervals. Acute cortisol effects were
      studied by sampling at several time-points during isolation. Between 12 and 24
      weeks of age, basal cortisol concentrations decreased and a rather stable and
      adult circadian rhythm was reached at 20 weeks of age. Average basal cortisol
      concentrations were higher in barrows than in gilts. Furthermore, after
      isolation, the amplitude of the rhythm was increased in barrows but was unchanged
      in gilts. The rhythm was more unstable and the maximum value tended to shift only
      after evening isolation. Stressor timing, but also age, was found to affect
      average cortisol concentrations. Moreover, stressor timing was important for the
      acute cortisol response: the increase was higher in the morning. The results of
      this study emphasize the importance of considering the circadian rhythmicity of
      cortisol, in relation to age, gender, and (time of) stressor application, when
      studying the cortisol response of animals to stressors.

PMID- 9272676
TI  - Analysis of locomotor activity in the rat: parallelism index, a new measure of
      locomotor exploratory pattern.
AB  - Several measures of locomotor activity in rats, including the distance covered,
      movement time, speed of progression, and sinuosity showed significant changes in
      extreme situations after prolonged preadaptation or after stimulation with I.P.
      amphetamine. The same measures, however, either did not change or poorly
      reflected the changes in locomotor activity consistent with progressive
      habituation in successive daily or weekly recordings. Other movement parameters,
      such as the average angle of turns, did not change or changed marginally, even in
      extreme situations. A new locomotor parameter, the parallelism index, has been
      proposed. It reflects the overall tendency to turn and the angular magnitude of
      turns. The parallelism index is not directly dependent on the distance covered by
      the animal, and seems to significantly reflect subtle changes in the pattern of
      locomotor activity that is characteristic of the exploration of an unfamiliar
      environment compared to the locomotor movement in frequently visited areas. A
      significant decrease of the parallelism index with time or repeated exposure to
      the cage indicates that rats perform more turns, and/or more turns under larger
      angles, in a more familiar or a more explored environment. It is postulated that
      the parallelism index decreases with the familiarity of the area being explored.

PMID- 9272675
TI  - Adrenalectomy increases sensitivity to central insulin.
AB  - When infused into the third ventricle of rats, insulin dose-dependently reduces
      food intake and body weight, with doses of 1 mU/day and lower being ineffective.
      Because corticosterone functionally antagonizes many of insulin's peripheral
      actions, and because corticosterone acts in the brain to enable hyperphagia under
      some conditions, a subthreshold dose of insulin (1 mU/day), or its saline
      vehicle, was infused into the third ventricle of adrenalectomized (ADX) and sham
      ADX male Long-Evans rats. Sham-ADX rats that received insulin or saline had no
      significant change of food intake or body weight over a 2-week interval.
      Likewise, saline-infused ADX were unaffected. In contrast, ADX rats receiving
      insulin had a significant reduction of food intake and body weight. These results
      suggest that the absence of circulating glucocorticoids increases the brain's
      sensitivity to insulin, and that insulin in the brain acts to lower food intake
      and body weight via a glucocorticoid-sensitive mechanism.

PMID- 9272677
TI  - Differences in the stress response of Wistar-Kyoto (WKY) rats from different
      vendors.
AB  - Wistar-Kyoto (WKY) rats are hyperresponsive to stress and prone to stress ulcer.
      However, some variability in these general findings has been reported. This
      variability may reflect differences in the rat stock from different WKY rat
      vendors. WKY rats from Taconic (WKY-T), Harlan Sprague-Dawley (WKY-H), and
      Charles River (WKY-CR) were observed in the open-field test (OFT) and the forced
      swim test (FST), and subsequently exposed to ulcerogenic water-restraint stress.
      There were no differences between vendor stocks in the FST, but WKY-CR rats were
      significantly more immobile in the OFT as compared to WKY-T and a Wistar control
      group. WKY-CR and WKY-H rats revealed significantly more ulcers as compared to
      WKY-T and Wistar rats. The WKY inbreeding programs at Charles River and Harlan,
      as compared to the outbreeding practice at Taconic may contribute to these vendor
      differences. These data indicate that WKY rat sublines from different vendors
      represent an important source of variability when comparing studies of stress
      reactivity using WKY rats.

PMID- 9272678
TI  - Nontasters, tasters, and supertasters of 6-n-propylthiouracil (PROP) and hedonic
      response to sweet.
AB  - Genetic sensitivity to 6-n-propylthiouracil (PROP) has been reported to predict
      hedonic response to sweet taste in both women and men. This study was based on a
      sample of 159 women of different ethnic backgrounds, mean age 27.0 years, and
      mean body mass index (BMI) 23.2. The women were classified as nontasters (n =
      43), regular tasters (n = 70), or supertasters (n = 46) of PROP on the basis of
      their PROP detection thresholds and the scaling of 5 suprathreshold solutions of
      PROP and NaCl. Nontasters had thresholds > 1.8 x 10(-4) mol/L PROP and PROP/NaCl
      ratios < 1.60. Supertasters had thresholds < 3.2 x 10(-5) mol/L PROP and
      PROP/NaCl ratios > 1.60. Genetic sensitivity to PROP failed to predict sweetness
      intensity ratings or hedonic response profiles for sucrose solutions. Separating
      subjects into sucrose "likers" and "dislikers" failed to reveal any significant
      links to PROP nontaster, taster, or supertaster status in this all-female sample.

PMID- 9272679
TI  - Learning in the Africanized honey bee: Apis mellifera L.
AB  - Several series of experiments are reported that investigate learning in the
      Africanized honey bee. In the first series, classical conditioning of proboscis
      extension was studied by confining bees to small metal tubes where they received
      pairings of an odor with a 3-s feeding of sucrose. After a number of odor-sucrose
      pairings, the bees began to extend their proboscis to the odor. Controls include
      Unpaired, Discrimination, and Pseudoconditioning Groups. This technique was used
      to look at conditioning to a light CS, and to the odors of beeswax, geraniol,
      citral, and hexanal. The results indicate that acquisition was best when sucrose
      was paired with the odor of beeswax. Conditioning to the remaining odors was
      roughly similar, but acquisition did not occur using a light. In a second series
      of experiments, odors were no longer followed by sucrose feedings and the
      conditioned response slowly disappeared. With the exception of geraniol as a CS,
      this extinction effect did not occur if the animals continued to be fed on an
      unpaired schedule. In a third series of experiments, conditioned inhibition was
      demonstrated when geraniol was used as conditioned stimuli, but no effect was
      found when the odors of hexanal, citral and wax were used. In a fourth series of
      experiments, unrestrained bees flew back and forth from the laboratory to the
      hive, where they were taught to distinguish targets based on color and odor. With
      this technique, color and odor discrimination in the Africanized bees was
      demonstrated. In addition, it was found that more intruder bees visited the
      experimental station when the stimuli used were olfactory rather than visual.

PMID- 9272680
TI  - Functional relationship between the hypothalamic vigilance area and PAG vigilance
      area.
AB  - The vigilance reaction is characterized by a large bradycardia, a pressor
      response, and inspiratory apnea in anesthetized rabbits and the inhibition of
      movement in conscious rabbits. This affective response pattern can be elicited by
      electrical stimulation of the dorsolateral hypothalamus (the hypothalamic
      vigilance area) or the ventrolateral periaqueductal gray (the periaqueductal gray
      vigilance area). The present study sought to advance our understanding of the
      functional relationship between the hypothalamic vigilance area (HVA) and the
      periaqueductal gray vigilance area (PVA) by measuring the effects of transverse
      transections of the caudal portion of the ventrolateral PAG (vlPAG) upon the
      cardiovascular responses elicited from the dorsolateral hypothalamus and the
      rostral vlPAG. Selective transverse transections of the caudal vlPAG
      significantly reduced the magnitudes of the bradycardia and pressor response
      elicited by stimulation of the PVA rostral to the transection site, but had
      minimal impact on the cardiovascular responses evoked by stimulation of the HVA.
      These findings suggest that the cardiovascular responses elicited by stimulation
      of the vlPAG are mediated by a neural pathway that is parallel, at least in part,
      to the one that subserves the response elicited from the HVA. The results also
      provide support for the view that the PAG is not an essential structure in the
      mediation of the autonomic components of affective behaviors involving behavioral
      inhibition.

PMID- 9272681
TI  - Regulation of stimulatory adenylyl cyclase signaling during forskolin-induced
      differentiation of mouse neuroblastoma x rat glioma (NG108-15) cells.
AB  - Chronic exposure of neuroblastoma x glioma (NG108-15) cells to substances that
      elevate intracellular cAMP levels results in morphological differentiation into a
      more neuronal-like phenotype. Here we report that forskolin-induced
      differentiation is accompanied by a biphasic regulation of stimulatory adenylyl
      cyclase (AC) signaling. While 1 day of forskolin exposure produces an initial
      increase in basal, [AIF4](-)-, and prostaglandin E1 (PGE1)-stimulated AC
      activities, stimulatory signal transduction is substantially reduced after
      complete differentiation of the cells (6 days). Western blot analysis revealed
      that these functional changes correlate well with changes in the quantity of
      G(s)alpha, the stimulatory component of AC. Additional forskolin-induced
      adaptations were found for PGE1 receptors, inhibitory G proteins and AC. These
      data demonstrate that neuronal differentiation of NG108-15 cells is associated
      with complex regulatory changes within the stimulatory PGE1 receptor system.

PMID- 9272683
TI  - Association of the apolipoprotein A-IV codon 360 mutation in patients with
      Alzheimer's disease.
AB  - Specific apolipoprotein E (apoE) alleles determines, in large part, the risk and
      mean age of onset familial and sporadic Alzheimer disease. The unresolved issues
      in this relationship support the contribution of other environmental and genetic
      parts. Among the candidates the apolipoprotein A-IV (apoA-IV) a component of
      plasma lipid particles similar to apoE has been suggested to play a role in brain
      metabolism. Since apoA-IV has a common DNA based protein polymorphism with a
      different function we determined apoA-IV (360:Gln:His) DNA polymorphism in 63
      late-onset sporadic Alzheimer's patients. We found that the APOA-IV (360:His)
      heterozygosity occurs significantly more frequent (20.6% vs. 7.0%, P = 0.021,
      odds ratio 3.4 (confidence interval 1.1-10.2)) comparing age-matched controls
      with normal mental score. The significant difference in apoA-IV allelic
      distribution has been detected dominantly in patients with non-apoE4 genotype.
      Our data indicate that the apoA-IV-2 allele may confer one of the susceptibility
      markers for Alzheimer's disease (AD) and strengthen the polygenic risk
      determination of the variability in expression of AD.

PMID- 9272682
TI  - Melatonin and vitamin E limit nitric oxide-induced lipid peroxidation in rat
      brain homogenates.
AB  - We have investigated the level of lipid peroxidation (LPO) in rat brain
      homogenates in the presence of nitric oxide (NO) which was released by the
      addition of sodium nitroprusside (SNP) and compared it with that induced by H2O2.
      We also examined the effect of melatonin and vitamin E on the NO-induced LPO. The
      concentration of malonaldehyde (MDA) plus 4-hydroxyalkenals (4-HDA) was used as
      an index of LPO. While both H2O2 and SNP increased MDA + 4-HDA production in
      brain homogenates in a concentration-dependent manner, SNP was more potent than
      H2O2 at all concentrations tested. Both melatonin or vitamin E reduced NO-induced
      LPO in a dose-dependent manner in concentrations ranging from 10 microM to 10 mM.
      Under the in vitro conditions of this experiment, vitamin E was more efficient
      than melatonin in limiting NO-induced LPO in rat brain homogenates.

PMID- 9272684
TI  - Increase of catechol-O-methyltransferase activity in rat brain microglia after
      intrastriatal infusion of fluorocitrate, a glial toxin.
AB  - Striatal catechol-O-methyltransferase (COMT), monoamine oxidase B (MAO-B; an
      astroglial enzyme), alkaline phosphodiesterase I (PDE; a microglia/macrophage
      marker) and tyrosine hydroxylase (TH; catecholaminergic neuron marker) activities
      were analyzed biochemically 1-3 days after infusion of fluorocitrate, an
      astrocyte damaging agent. Astrocytes, microglia and neurons were stained
      immunohistochemically with specific antibodies (against glial fibrillary acidic
      protein, OX-42 and TH, respectively) and with COMT antiserum. Three days after
      fluorocitrate infusion the activity of MAO-B was reduced, whereas COMT and PDE
      activities were increased. The elevation of COMT immunoreactivity co-localized to
      microglial cells, but not to astrocytes. In conclusion, this is the first report
      indicating that microglia contains COMT activity which may be increased in
      pathological conditions.

PMID- 9272685
TI  - Evidence for a physiological role of central calcitonin gene-related peptide
      (CGRP) receptors in the control of food intake in rats.
AB  - In the present study, we investigated the role of central calcitonin gene-related
      peptide (CGRP) and amylin receptors in mediating the anorectic effects of CGRP
      and amylin in rats chronically cannulated in the lateral brain ventricle.
      Intracerebroventricular (ICV) injection of the CGRP and amylin receptor
      antagonist CGRP(8-37) failed to influence the anorectic effects of peripherally
      injected CGRP and amylin. CGRP(8-37) alone, however, increased food intake in
      food deprived rats when administered 2 h before food presentation. Under the same
      experimental conditions, the more specific amylin receptor antagonists amylin(8
      37) or AC 187 did not affect food intake. We therefore conclude, that CGRP is a
      physiological regulator of food intake within the central nervous system, acting
      at central CGRP receptors. Peripheral receptors, however, are likely to mediate
      the anorectic effects of peripherally administered amylin and CGRP.

PMID- 9272686
TI  - Differential effects of dimethyl sulfoxide on nicotinic acetylcholine receptors
      from mouse muscle and Torpedo electrocytes.
AB  - The present study examined the effects of 0.1% dimethyl sulfoxide (DMSO) on
      nicotinic acetylcholine receptors (nAChR) from mouse muscle and Torpedo
      californica electrocytes. Receptors were expressed in Xenopus laevis oocytes and
      studied with voltage-clamp. When applied simultaneously with acetylcholine, DMSO
      did not inhibit current amplitude of either receptor. Preincubation with DMSO for
      1 min reduced current amplitude by approximately 50% from oocytes expressing
      electrocyte receptor. Preincubation did not affect the muscle receptor. With
      electric organ membranes, 0.1% DMSO did not block either [alpha
      (125)I]bungarotoxin binding to the nAChR agonist site or [3H]phencyclidine
      binding to its high affinity site on resting or desensitized receptor. These data
      suggest that DMSO might be affecting the electrocyte receptor through a second
      messenger system.

PMID- 9272687
TI  - Trophic action of pharmacological substances with a guanidine group on mouse
      neuroblastoma cells and chick ganglionic neurons in culture.
AB  - A series of substances (designated CTQ compounds) with a guanidine group have
      been synthesized and tested for their ability to promote neuronal survival and
      neurite outgrowth. Mouse neuroblastoma clonal cell lines grown in serum
      containing medium for 10 days as well as primary cultures of embryonic chicken
      ganglion neurons grown in serum-free defined medium for 1 or 2 days have been
      used for the experiments. Among the various CTQ compounds (CTQ1-CTQ20) tested,
      only CTQ8 exerted positive neurotrophic effects on these peripheral neuronal
      cells. At a concentration of 10(-4) M, CTQ8 enhanced neuritogenesis of
      neuroblastoma cells. However, the most striking influence of CTQ8 was its
      promoting effect (6- to 10-fold) on the survival of chicken ciliary and dorsal
      root ganglionic neurons at concentrations ranging from 10(-3) M to 5 x 10(-4) M.

PMID- 9272688
TI  - Subfornical organ efferents enhance extracellular noradrenaline concentrations in
      the median preoptic area in rats.
AB  - The present study was carried out to examine whether angiotensinergic pathways
      from the subfornical organ (SFO) regulate the noradrenergic system in the median
      preoptic nucleus (MnPO). Intracerebral microdialysis techniques were used to
      quantify the extracellular concentration of noradrenaline (NA) in the MnPO area.
      In urethane-anesthetized male rats, electrical stimulation (5-20 Hz, 0.6 mA) of
      the SFO significantly increased the NA concentration in the MnPO area, and the
      increase was significantly diminished by pretreatment with the angiotensin II
      (ANG II) antagonist saralasin (Sar; 5 microg), into the third ventricle (3V).
      Injections of ANG II (5 microg) into the 3V significantly enhanced NA release in
      the MnPO area. The data imply that the angiotensinergic pathways from the SFO to
      the MnPO may act to enhance NA release in the MnPO area.

PMID- 9272689
TI  - Bilateral kainic acid lesions in the rat hilus induce non-linear additive mossy
      fiber neoinnervation.
AB  - Kainic acid (KA) lesions of the rat hilus model hippocampal sclerosis and
      temporal lobe epilepsy. Unilateral hilar cell loss denervates the associational
      afferents normally projecting to the inner molecular layer (IML) granule cell
      dendrites, followed by ipsilateral mossy fiber (MF) sprouting. Hilar neurons also
      project through the hippocampal commissure to the contralateral IML. This study
      compared densities of IML MF sprouting following unilateral versus bilateral low
      dose KA lesions, using Neo-Timm stain 30 days later. Unilateral KA (0.4 microg)
      caused only dense ipsilateral MF sprouting. Bilateral lesions with lower doses of
      KA (0.1 with 0.2 or 0.3 microg) induced dense bilateral MF sprouting. However,
      the same low doses of KA injected unilaterally did not induce significant
      sprouting ipsilaterally or contralaterally. These data show that denervations of
      both associational and commissural afferents to the same IML dendritic zones of
      granule cells induce non-linear, additive bilateral MF neoinnervations.

PMID- 9272690
TI  - Enhancement of an inhibitory input to the feeding central pattern generator in
      Lymnaea stagnalis during conditioned taste-aversion learning.
AB  - To study the neuronal mechanism of a conditioned taste-aversion (CTA) learning in
      the pond snail Lymnaea stagnalis, we examined the synaptic connection between the
      neuron 1 medial (N1M) cell and the cerebral giant cell (CGC), the former is an
      interneuron in central pattern generator for the feeding response and the latter
      is a regulatory neuron to the central pattern generator. Inhibitory postsynaptic
      potential (IPSP) which was evoked in the N1M cell by activation of the CGC was
      larger and lasted longer in the conditioned animal than that in the control
      animal. The electrical properties of the cell body of CGC and the responses of
      the CGC to the chemosensory inputs were not changed during the CTA learning.
      These results, together with the previous report indicating the existence of
      excitatory projection from the N1M cell to the feeding motoneuron, suggest that
      enhanced IPSP in the N1M cell may underlie the suppression of feeding responses
      in the Lymnaea CTA learning.

PMID- 9272691
TI  - A patch clamp study of a glutamatergic chloride channel on pharyngeal muscle of
      the nematode Ascaris suum.
AB  - Glutamatergic chloride channels on the pharyngeal muscle of Ascaris suum could be
      activated with glutamate and ivermectin and reversibly blocked with picrotoxin
      using the patch clamp technique. No activation was observed with GABA, glycine
      and acetylcholine. Most of the current was carried by the main subconductance
      state of 21 pS. Two smaller subconductance states occurred rarely. Open time
      histograms could be best fitted by two time constants of tau(o1) = 0.33 ms and
      tau(o2) = 9.8 ms present at all glutamate concentrations applied. The results
      suggest that some properties of the channel investigated here are different from
      other glutamatergic chloride channels reported from various animals.

PMID- 9272692
TI  - The decreased susceptibility to the development of in vitro kindling-like state
      in hippocampal CA1 slices of rats sensitive to audiogenic seizures.
AB  - The field excitatory postsynaptic potential (fEPSP) with the presynaptic fiber
      volley (PrV) and the population spike (PS) were recorded with two glass
      microelectrodes in stratum radiatum and stratum pyramidale of rat hippocampal CA1
      slices, respectively, in response to electric stimulation of Schaffer
      collaterals/commissural fibers (SC/CF) containing glutamate as a
      neurotransmitter. Three components of the overall input-output function were
      taken: (1) PrV amplitude vs. intensity of stimulating current, (2) dendritic
      layer fEPSP slope vs. PrV amplitude and (3) PS amplitude vs. fEPSP slope. Three
      groups of rats were used: (1) normal male Wistar rats (control), (2) a strain of
      rats genetically-prone to audiogenic seizures (GPAS) and (3) GPAS rats 10 min
      after a single intense sound stimulus. Unlike hippocampal slices taken from
      normal Wistar rats, slices taken from GPAS rats were less susceptible to the
      development of the in vitro kindling-like state induced by the repeated 30 s
      applications (3 episodes) of [K+]o up to 20 mM. Such short-term [K+]o increases
      also did not induce the EPSP-spike transfer potentiation (E-S potentiation) in
      CA1 pyramidal neurons of audiogenic rats either. Furthermore, the presynaptic
      glutamatergic fibers of GPAS rats are less excitable to stimulating currents then
      that of normal Wistar rats. It is suggested that the resistance of audiogenic rat
      hippocampal CAI slices to the development of long lasting epileptiform activity
      is a protective adaptive mechanism preventing the propagation of seizure activity
      into limbic structures.

PMID- 9272693
TI  - Initial cyclosporin A but not glucocorticoid treatment promotes recovery of
      striatal dopamine concentration in 6-hydroxydopamine lesioned mice.
AB  - We examined the effects of cyclosporin A (CsA) and glucocorticoid (GC;
      hydrocortisone sodium succinate) in a mouse model of experimental parkisonism. GC
      or CsA was administered 30 or 60 min, respectively, prior to
      intracerebroventricular injection of 6-hydroxydopamine, followed by injection of
      a similar dose of each drug 3 h later. CsA reduced the extent of depletion of
      striatal concentrations of dopamine (DA) and dihydroxyphenylacetic acid (DOPAC)
      associated with dopaminergic neuronal degeneration. GC reduced the extent of
      homovanillic acid (HVA) depletion in the same region. A combination treatment
      with CsA and GC did not produce a further enhancement of the recovery of striatal
      concentrations of monoamines observed with CsA only. Our findings demonstrated
      the beneficial effects of initial CsA treatment in experimental models of
      parkinsonism and further support the usefulness of CsA in the treatment of
      Parkinson's disease.

PMID- 9272694
TI  - Effects of pyramidal tract stimulation on forelimb flexor motoneurons during
      fictive locomotion in cats.
AB  - To investigate spinal mechanisms of control of locomotion by the pyramidal
      system, we made intracellular recording from forelimb flexor motoneurons, and
      analyzed excitatory postsynaptic potentials (EPSPs) evoked by stimulation of the
      medullary pyramid during forelimb fictive locomotion in immobilized, decerebrate
      cats. We observed that (1) pyramidal stimulation evoked disynaptic EPSPs, (2)
      which were much bigger in the locomotor state than in the resting state, and that
      (3) the pyramidal EPSPs were rhythmically modulated, so that the facilitation
      occurred in the flexor-active phase. Last-order neurons mediating pyramidal
      effects presumably receive rhythmic input from the spinal locomotor network.

PMID- 9272695
TI  - Increase in levels of total free fatty acids in rat brain regions following 3
      nitropropionic acid administration.
AB  - Acute exposure to a neurotoxin, 3-nitropropionic acid (3-NPA), in rats results in
      an increase in total free fatty acid (FFA) concentration in selective brain
      regions. We investigated the effect of 3-NPA administration on the cerebral
      concentrations of FFA used as a marker of oxidative stress. Rats (n = 3/group)
      were dosed subcutaneously (s.c.) either with a vehicle (phosphate buffer) or 3
      NPA in phosphate buffer at 30 mg/kg body weight. Animals were sacrificed after 1,
      2, 3, and 6 h of injection. Brains were then dissected into frontal cortex (FC),
      caudate nucleus (CN), and hippocampus (HIP). The concentration of total FFA
      increased from 130 to 300% within 1-2 h after 3-NPA injection in all brain
      regions when compared with the baseline level obtained from the control rats and
      taken as 100%. In CN, FFA returned to the baseline level within 3 h of treatment.
      However, in FC and HIP the concentration of FFA remained significantly elevated
      above the baseline until 6 h. The released FFA provide a substrate for free
      radicals formation. The results of this study suggest a role of oxidative stress
      in the mechanism of 3-NPA toxicity.

PMID- 9272696
TI  - Effects of chronic isoproterenol treatment or submandibular and sublingual
      ablation on microflora of mouse tooth surfaces.
AB  - BALB/cA mice were examined for the effects of chronic isoproterenol treatment or
      submandibular-sublingual gland ablation on the natural patterns of oral bacterial
      colonization on tooth surfaces. Indigenous microflora on the tooth surfaces of
      BALB/cA mice was relatively simple. The predominant bacterial groups were
      Enterobacteriaceae (45.9%), enterococci (29.4%) and staphylococci (15.7%).
      Isoproterenol, which resulted in the induced synthesis of proline-rich proteins,
      caused a decrease in the total cultivable bacteria on the tooth surfaces. The
      proportion of Enterobacteriaceae in the isoproterenol-treated mice decreased,
      although the proportion of other bacterial groups increased. Salivary gland
      ablation, which caused the loss of mucins in saliva, showed essentially the same
      number of total bacteria as the control. Salivary gland ablation resulted in a
      decrease in the proportion of Enterobacteriaceae, while the proportion of Gram
      positive rods and staphylococci increased.

PMID- 9272697
TI  - Production of monoclonal antibody discriminating serological difference in
      Escherichia coli O9 and O9a polysaccharides.
AB  - A monoclonal antibody (mAb) with a unique antigenic specificity against
      Escherichia coli O9 was produced. The O9a mAb was reactive with a part of the
      strains in E. coli O9. The O9a mAb did not react with LPS from the E. coli O9
      test strain Bi316-42. The distribution of the antigen defined by the O9a mAb in
      E. coli O9 was consistent with that of E. coli O9a present in E. coli O9 strains.
      The chemical structure of the repeating unit of the O-specific polysaccharide
      detected by the mAb was demonstrated to be a mannotetraose by two-dimensional
      nuclear magnetic resonance spectroscopy. It was confirmed that the mAb recognized
      E. coli O9a serotype in E. coli O9 serotype strains, suggesting that E. coli O9a
      serotype might be a dominant strain in E. coli O9.

PMID- 9272698
TI  - Lambda-toxin of Clostridium perfringens activates the precursor of epsilon-toxin
      by releasing its N- and C-terminal peptides.
AB  - The effect of lambda-toxin, a thermolysin-like metalloprotease of Clostridium
      perfringens, on the inactive epsilon-prototoxin produced by the same organism was
      examined. When the purified epsilon-prototoxin was incubated with the purified
      lambda-toxin at 37 C for 2 hr, the 32.5-kDa epsilon-prototoxin was processed into
      a 30.5-kDa polypeptide, as determined by SDS-polyacrylamide gel electrophoresis.
      A mouse lethality test showed that the treatment activated the prototoxin: the
      50% lethal doses (LD50) of the prototoxin with and without lambda-toxin treatment
      were 110 and 70,000 ng/kg of body weight, respectively. The lethal activity of
      the prototoxin activated by lambda-toxin was comparable to that with trypsin plus
      chymotrypsin and higher than that with trypsin alone: LD50 of the prototoxin
      treated with trypsin and trypsin plus chymotrypsin were 320 and 65 ng/kg of body
      weight, respectively. The epsilon-toxin gene was cloned and sequenced.
      Determination of the N-terminal amino acid sequence of each activated epsilon
      prototoxin revealed that lambda-toxin cleaved between the 10th and 11th amino
      acid residues from the N-terminus of the prototoxin, while trypsin and trypsin
      plus chymotrypsin cleaved between the 13th and 14th amino acid residues. The
      molecular weight of each activated epsilon-prototoxin was also determined by
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The
      C-terminus deduced from the molecular weight is located at the 23rd or 30th amino
      acid residue from the C-terminus of the prototoxin, suggesting that removal of
      not only N-terminal but also C-terminal peptide is responsible for activation of
      the prototoxin.

PMID- 9272699
TI  - Japanese encephalitis virus infection in Vero cells: the involvement of
      intracellular acidic vesicles in the early phase of viral infection was observed
      with the treatment of a specific vacuolar type H+-ATPase inhibitor, bafilomycin
      A1.
AB  - The involvement of intracellular acidic vesicles in the early phase of Japanese
      encephalitis (JE) virus infection in Vero cells was observed by adding a specific
      vacuolar type H+-ATPase (V-ATPase) inhibitor (bafilomycin A1) in the cell culture
      medium. Studies with the detection of viral envelope (E) protein suggested that
      bafilomycin A1 inhibited virus infection in the cells. Subcellular distribution
      of incoming biotinylated virions and 3H-uridine-labeled viral RNA were observed
      in fractions of a Percoll density gradient. At 10 min of the chasing period,
      virions and viral RNA were found mainly in fractions with a mean density of 1.04
      g/ml corresponding to the endosome both in the control and bafilomycin A1-treated
      cells. At 60 min of the chasing period, the peak of biotin activity was detected
      in fractions with a mean density of 1.08 g/ml corresponding to the lysosome,
      whereas the peak of radioactivity did not run parallel with that of biotin and
      shifted to fractions with a mean density of 1.05 g/ml and higher than 1.084 g/ml,
      respectively. At 60 min of the chasing period in bafilomycin A1-treated cells,
      the peak of biotin and radioactivity were still found mainly in the fraction with
      a density of 1.04 g/ml, representing the endosome. Subcellular fractionation by a
      Percoll density gradient revealed that bafilomycin A1 treatment resulted in the
      accumulation of virions in the endosome fraction and suggested the prevention of
      intracellular translocation of the virions which occurs during the early entry
      process of an infecting virus to the cells.

PMID- 9272700
TI  - Pathogenicity of glycoprotein C-deficient herpes simplex virus 1 strain TN-1
      which encodes truncated glycoprotein C.
AB  - A clinical isolate of herpes simplex virus 1 (TN-1) from a stromal keratitis
      patient was found to be defective in the glycoprotein C (gC) gene (UL44), thus
      resulting in the production of truncated gC upon infection. To study the
      pathogenetic role of truncated gC, we prepared a recombinant LTN-8 derived from
      TN-1 with deletions of the 1.5 kilobase pairs of the gC gene including the
      initiation codon. A penetration assay revealed LTN-8 to be less efficient in its
      penetration ability than TN-1, the laboratory strain KOS and RTN-1-20-3, a
      recombinant derived from TN-1 with the KOS gC gene. The penetration of LTN-8 was
      facilitated by the addition of TN-1-infected culture medium. TN-1 virus
      preparations had no hemagglutinating activity. However, the animals infected with
      TN-1 did develop hemagglutination inhibition (HI) antibodies. The LTN-8-infected
      animals did not develop HI antibodies. The pathogenicity in BALB/c mice following
      either corneal, intraperitoneal or intracerebral inoculation did not
      significantly differ among TN-1, RTN-1-20-3 or LTN-8. Our results indicate that
      truncated gC was sufficient for the induction of HI antibodies and was also able
      to facilitate penetration in vitro. Although truncated gC might be a virulence
      factor acting as a decoy, both truncated gC and intact gC had little effect on
      the outcome following intracerebral, intraperitoneal or corneal inoculation.

PMID- 9272701
TI  - Heat shock cognate protein 71-associated peptides function as an epitope for
      Toxoplasma gondii-specific CD4+ CTL.
AB  - HLA-DR-restricted CD4+ cytotoxic T-lymphocyte (CTL) lines specific for Toxoplasma
      gondii (T. gondii)-infected melanoma cells have been established from peripheral
      blood lymphocytes (PBLs) of a patient with chronic toxoplasmosis. The role of
      heat shock cognate protein (HSC) 71 in antigen (Ag) processing and presentation
      of T. gondii-infected melanoma cells to these CD4+ CTL lines was investigated. A
      human melanoma cell line (P36) pulsed with T. gondii-infected P36 cell-derived
      HSC71 was lysed by a T. gondii-specific CD4+ CTL line (Tx-HSC-1). The Tx-HSC-1
      also killed T. gondii-infected P36 cells. The lytic activity of Tx-HSC-1 against
      P36 cells pulsed with T. gondii-infected P36 cell-derived HSC71 was inhibited by
      monoclonal antibodies (mAbs) against HSC71. Anti-human leukocyte antigen (HLA)-DR
      mAb also partially blocked the lytic activity, whereas anti-HLA-A,B,C mAb did not
      block the lytic activity. In addition, a flow cytometric analysis with these
      specific mAbs against HSC71 showed HSC71 to be expressed on the cell surface of
      T. gondii-infected P36 cells as well as uninfected P36 cells. These data indicate
      that HSC71 molecules are expressed on human melanoma cell line P36, and that
      HSC71 may play a potential role in Ag presentation and processing of T. gondii
      infected P36 cells to CD4+ CTL.

PMID- 9272702
TI  - MHC class I presentation of an exogenous polypeptide antigen encoded by the
      murine AIDS defective virus.
AB  - Peptides derived from endogenous proteins are presented by MHC class I molecules,
      whereas those derived from exogenous proteins are presented by MHC class II
      molecules. This strict segregation has been reconsidered in recent reports in
      which exogenous antigens are shown to be presented by MHC class I molecules in
      the phagocytic pathway. In this report, the presentation pathway of an
      exogenously added highly antigenic polypeptide encoded by the murine AIDS (MAIDS)
      defective virus gag p12 gene is investigated. A 25-mer polypeptide (P12-25)
      encoded within the gag p12 region of the MAIDS defective virus was found to be
      effective in stimulating unprimed B6 (H-2b) CD8+ T cells in vitro. The
      presentation of P12-25 is sensitive to cytochalasin B and D, brefeldin A and
      gelonin, a ribosome-inactivating protein synthesis inhibitor, but less sensitive
      or resistant to lactacystin, a highly specific inhibitor of the proteasome.
      Interestingly, CA-074, a selective inhibitor of cathepsin B, inhibited
      presentation of the polypeptide, indicating its involvement in the degradation of
      the P12-25 polypeptide. In fact, when P12-25 was digested with purified cathepsin
      B in vitro, a highly antigenic 11-mer peptide containing the class I (H-2Db)
      binding motif was obtained. Our results favor the phagosome/macropinosome-to
      cytosol-to-endoplasmic reticulum (ER)-to-cell surface pathway for exogenous
      antigens presented by MHC class I molecules. These findings may be relevant to
      exploiting peptide vaccines that specifically elicit CD8+ T cell immunity in
      vivo.

PMID- 9272703
TI  - Partial sequences of large subunit ribosomal DNA of a new yeast species,
      Trichosporon domesticum and related species.
AB  - We determined the partial sequences of large subunit rDNA of a new yeast species,
      Trichosporon domesticum, which was isolated from the house of a summer-type
      hypersensitivity pneumonitis patient. Phylogenetically, T. domesticum was
      positioned in the taxonomic group containing T. montevideense and T. brassicae,
      which indicated an identical serotype. A phylogenetic relationship among all
      species of the genus Trichosporon which belong to the basidiomycetous yeast is
      clarified.

PMID- 9272704
TI  - cDNA cloning and characterization of rat C5a anaphylatoxin receptor.
AB  - Activation of the complement cascade plays an essential role in the early stages
      of inflammation. C5a and its receptor are particularly active in anaphylaxis. To
      determine the pathological roles played by C5a and C5a receptor (C5aR) in rats,
      we cloned C5aR cDNA and analyzed distribution of its mRNA in various organs
      including lung from an LPS-stimulated rat. Furthermore, we generated a polyclonal
      antiserum which specifically recognizes rat C5aR, as confirmed by its specific
      interaction with cells transfected with rat C5aR cDNA.

PMID- 9272705
TI  - Geographic distribution of French-Canadian low-density lipoprotein receptor gene
      mutations in the Province of Quebec.
AB  - A total of 35 homozygous and 1320 heterozygous patients with familial
      hypercholesterolemia (FH) was screened for the presence of six low-density
      lipoprotein receptor (LDLR) gene mutations previously reported among French
      Canadians. The geographic distribution of patients' birthplaces and the relative
      prevalence of these six mutations in the LDLR gene in the province of Quebec were
      compared. For this purpose, the 16 administrative regions of the province of
      Quebec were grouped into seven geographic regions. The relative frequency of the
      six mutations differed in the seven regions: the > 15 kb deletion (delta > 15 kb)
      had the highest relative frequency in the Bas St-Laurent/Gaspesie region, and the
      point mutation in exon 3 had the highest relative frequency in the Saguenay-Lac
      St-Jean/Cote-Nord region. In the Montreal area, the delta > 15 kb and the
      mutation in exon 3 had prevalence rates of 71.2% and 13.0%, respectively, whereas
      the relative frequencies of the delta > 15 kb and the point mutation in exon 3 in
      the Quebec city region were 57.5 and 21.8%, respectively. Finally, in Saguenay
      Lac-St-Jean/Cote-Nord, the relative frequency of the delta > 15 kb only reached
      31.5% and the point mutation in exon 3, 59.2%. Thus, on the north shore of the
      St. Lawrence River, the prevalence of the delta > 15 kb decreases from west to
      north-east, whereas the relative frequency of the mutation in exon 3 appears to
      increase. These observations provide a better characterization of FH among French
      Canadians of Quebec, a Canadian province with a high prevalence of this inherited
      disease.

PMID- 9272706
TI  - Scintigraphic evaluation of Tc-99m-low-density lipoprotein (LDL) distribution in
      patients with Gaucher disease.
AB  - Gaucher disease (GD) is frequently associated with reduced plasma levels of low
      density lipoproteins, presumably due to increased catabolism of LDL. The purpose
      of this study was to determine the distribution of Tc-99m LDL (Tc-LDL) in Gaucher
      patients, and compare the findings to bone marrow distribution. Four patients
      with non-neuropathic Gaucher disease (type 1) underwent baseline whole body
      imaging at 4 and 24 h after injection of dialyzed autologous LDL labeled with 10
      20 mCi Tc-99m-pertechnetate. Three of the four patients were treated with
      macrophage-targeted alglucerase (Ceredase). The LDL studies were compared to
      concurrent bone marrow scans performed with 10 mCi Tc-99m sulfur colloid (Tc-SC).
      Follow-up Tc-LDL and Tc-SC scans were obtained 12-14 months later. Tc-LDL
      activity was abnormally increased in the spleen and long bones of the upper and
      lower extremities. Liver activity was also increased. Prominent blood pool
      activity 4 h after injection mostly cleared on the 24-hour images. The
      distribution of Tc-SC was congruent with Tc-LDL activity. All patients had mild
      to-moderate hepatomegaly and peripheral bone marrow expansion. One patient had
      been previously splenectomized and the remaining three had moderate-to-severe
      splenomegaly. Two of the three treated patients showed regression of peripheral
      bone marrow activity with therapy, along with a comparable decrease in Tc-LDL
      uptake. Our study with Tc-LDL and Tc-SC suggests that in patients with Gaucher
      disease native LDL is taken up by the reticuloendothelial system (RES) of the
      spleen and bone marrow in addition to increased uptake by the liver. This
      abnormal uptake (presumably by macrophages of the RES) may account for
      accelerated LDL catabolism and reduced plasma levels of LDL. Serial LDL studies
      can be performed, allowing for longitudinal follow-up after drug or enzyme
      therapies.

PMID- 9272707
TI  - Incomplete penetrance and expressivity skewing in hereditary multiple exostoses.
AB  - Hereditary multiple exostosis (EXT) is an autosomal dominant skeletal disorder
      characterized by the formation of cartilage-capped prominences developing from
      the juxta-epiphyseal regions of the long bones and causing orthopedic deformities
      and occasionally sarcomatous degeneration. Reviewing a large cohort of 175 EXT
      patients referred to us over the last 40 years (1955-1995), we found 109 familial
      forms (62%) and 66 isolated cases (38%). The disease is consistently diagnosed
      before the age of 12 years and the risk of malignancy, although increased, is
      quite modest in our series (0.57%). The observation of seven unaffected
      individuals (six females, one male) with a family history and affected offspring
      supports the incomplete penetrance of the disease. Moreover, the observation of
      an unequal sex-ratio with a preponderance of males among probands in this series
      (103:72, p<0.02) and in all series reported to date (198:133, p<0.001) gives
      support to the variable penetrance of EXT genes among sexes. Whether this
      incomplete penetrance is associated with one of the disease genes recently
      identified in EXT is currently under investigation.

PMID- 9272708
TI  - Detection of dystrophin deletion carriers using FISH analysis.
AB  - The detection of carrier status in female relatives of Duchenne/Becker muscular
      dystrophy patients is not always possible and this poses a problem in genetic
      counseling. We have developed a simple method that can be used in families in
      which affected males are characterized by the presence of a deletion within the
      dystrophin gene. PCR fragments, corresponding to the deleted regions are used as
      fluorescent probes for hybridization of peripheral lymphocytes nuclei of female
      relatives. The results obtained clearly demonstrate the feasibility of this
      method for detecting female DMD/BMD carriers.

PMID- 9272709
TI  - Moving towards a syndrome: a review of 20 cases and a new case of non-mosaic
      tetrasomy 9p with long-term survival.
AB  - Tetrasomy 9p is a rare syndrome that has now been described in nearly a score of
      cases. We present a new case of i(9p) that presented to us early in infancy with
      significant dysmorphological features, including growth retardation, psycho-motor
      delay, hemifacial microsomia, auditory canal atresia, high-arched palate, bulbous
      nose, strabismus, epicanthic folds, congenital heart disease, dislocated hips,
      hypoplastic external genitalia, simian palmar creases, dysplastic nails and small
      digits. Chromosomal analysis revealed a 47,XX,idic(9)(q12) karyotype on GTG- and
      C-banding studies on peripheral blood lymphocytes. Fluorescent in situ
      hybridization (FISH) studies confirmed the origin of the extra chromosome. A
      review of the literature and a comparative analysis of the several well
      documented cases of i(9p) revealed a pattern of recurring features, including ear
      malformations, skeletal and joint problems (especially dislocations), hypoplasia
      of nails and digits, palatal abnormalities, hypertelorism, urogenital anomalies
      and developmental retardation. In the light of this analysis, we feel that
      tetrasomy 9p will soon be considered a clinically recognizable syndrome.

PMID- 9272710
TI  - A new multiple malformation syndrome of Mullerian dysgenesis and conductive
      hearing loss with facial hypoplasia, bilateral forearm deformity, brachydactyly,
      spinal stenosis and scoliosis.
AB  - Multiple congenital malformations in a young girl with bilateral conductive
      hearing loss are described. Facial dysmorphic features include prominent
      supraorbital ridges, facial hypoplasia, facial asymmetry, downward-slanting
      palpebral fissures, high prominent nasal bridge with bifid nasal tip and a small
      lower jaw, and hypoplastic ear lobules with bilaterally narrow and oblique
      external auditory canals. Recognisable skeletal abnormalities include hypoplastic
      facial bones, hypoplastic clavicles, narrow and anteriorly sloping shoulders,
      bowing of both forearm bones, brachydactyly due to short metacarpals and
      hypoplastic terminal phalanges, thoracolumbar kyphoscoliosis, narrow transverse
      measurements of most vertebrae with prominent coccyx, spinal canal narrowing,
      hypoplasia of lower ilia, medially bowed femora, tibiae and fibulae and
      brachysyndactyly of the second, third and fourth toes bilaterally. Gynaecological
      evaluation revealed abnormalities of the Mullerian duct structures: urogenital
      sinus, a vestigial uterus, a posteriorly placed small but patent vagina and a
      septum at the vaginal introitus. The pattern of MCA probably refers to a new
      syndrome within the "community of syndromes" involving anomalies of the Mullerian
      duct structures, limbs, spine and external ears.

PMID- 9272711
TI  - Cardio-facio-cutaneous (CFC) syndrome--a distinct entity? Report of three
      patients demonstrating the diagnostic difficulties in delineation of CFC
      syndrome.
AB  - We report on three patients with probable cardio-facio-cutaneous (CFC) syndrome.
      They present clinical findings of this condition such as: growth failure, heart
      defects, typical craniofacial appearance, ectodermal abnormalities, and
      developmental delay. We also give a detailed review of the previously published
      articles on CFC syndrome and discuss the differences between CFC, Noonan, and
      Costello syndromes. Other differential diagnoses are considered.

PMID- 9272712
TI  - Benign familial microcytic thrombocytosis with autosomal dominant transmission.
AB  - Familial thrombocytosis is an extremely rare disorder, so far reported in only a
      handful of families. In the majority of cases the characteristics were of
      essential thrombocythemia. Most patients presented with a platelet count above
      800,000/mm3, were diagnosed as having a myeloproliferative disease, and some
      required chemotherapy. We describe a benign form of familial thrombocytosis with
      autosomal dominant inheritance in five healthy members of three generations of a
      family, all of whom had moderate thrombocytosis within the range 422,000
      662,000/mm3, characterized by low mean platelet volume. A careful medical history
      and a 5-year follow up of the subjects did not reveal any untoward clinical
      development. This variant of familial thrombocytosis is therefore of a benign
      nature. Possible mechanisms linking thrombocytosis with platelet microcytosis in
      this family are discussed.

PMID- 9272713
TI  - Oto-facio-osseous-gonadal syndrome: a new form of syndromic deafness?
AB  - In this study, we report on two brothers, born to consanguineous parents, with a
      syndrome of sensorineural deafness, short stature, cryptorchidism, inguinal
      hernia, brachycephaly, prominent forehead, flat face, downslanting palpebral
      fissures, low nasal root, hypoplastic alae and round tip to the nose, low-set
      prominent ears, narrow thorax, genu valgum, wormian bones, fusion of carpal
      bones, delayed bone age and congenital clubfeet. This combination of anomalies
      appears to be a previously undescribed syndrome, with probable autosomal
      recessive inheritance.

PMID- 9272714
TI  - A patient with Edwards syndrome caused by a rare pseudodicentric chromosome 18 of
      paternal origin.
AB  - We present an unusual case of trisomy 18 due to a pseudodicentric chromosome 18
      of paternal origin. The karyotype was: 46,XY, -18, +psu dic(18)(qter-->cen-
      >p11.31::p11.31-->psucen-->qter). The origin of the abnormal chromosome was
      verified by FISH with a painting probe from chromosome 18. Absence of short-arm
      telomeres was shown by multicolor FISH, and the results of DNA analysis showed
      monosomy for loci D18S59 and D18S170 as well as paternal inheritance of the
      aberrant chromosome. The child's phenotype was characteristic of trisomy 18.

PMID- 9272715
TI  - Interstitial deletion 2(p11.2p13): a rare chromosomal abnormality.
AB  - We report on an infant with a karyotype of 46,XY,del(2) (p11.2p13), the fourth
      reported case in the literature. At birth, the child had eventration of the
      diaphragm. His phenotype was suggestive of a connective tissue disorder with
      scoliosis, pectus carinatum, long slender fingers, camptodactyly, cryptorchidism,
      hypertonia and myopia. His facial appearance was mildly dysmorphic and strongly
      resembled a previously reported patient with the same deletion. The child expired
      at 2 months of age. Some generalizations can be made about the phenotype for
      del(2)(p11.2p13), despite reporting of cases at different ages.

PMID- 9272716
TI  - Essential hyperhidrosis in Turner syndrome.
AB  - We describe two Turner patients suffering from severe essential hyperhidrosis.
      Since both disorders are rare (1 in 5000 live female births for Turner syndrome
      and approximately 1 in 1000 persons for essential hyperhidrosis), our finding of
      two patients with these disorders in a total of 150 essential hyperhidrosis
      patients may suggest that this association is more frequent in Turner syndrome
      than previously thought.

PMID- 9272717
TI  - A T > C transition causing a Leu > Pro substitution in a conserved region of the
      arylsulfatase A gene in a late infantile metachromatic leukodystrophy patient.
AB  - A T > C transition (L428P) was detected in the arylsulfatase A alleles of a late
      infantile metachromatic leukodystrophy patient. The mutation causes a Leu > Pro
      substitution in exon 8. It lies in a region conserved among arylsulfatases. The
      mutation was not detected in 37 other patients and in 57 normal controls.

PMID- 9272718
TI  - A polymorphism in intron 6 of the CYP17 gene.

PMID- 9272719
TI  - Neurotransmitter release evoked by alpha-latrotoxin in the smooth muscle of the
      female pig urethra.
AB  - Neuronal regulation of smooth muscle tone in the female pig urethra has mainly
      been studied in vitro using electrical field stimulation (EFS) of nerves.
      Excitatory control is considered to be exerted by released noradrenaline, whereas
      inhibitory control is non-adrenergic non-cholinergic (NANC), and mediated by
      nitric oxide (NO), and an as yet unidentified agent. We investigated the
      functional and morphological effects of alpha-latrotoxin (alphaLTX), a spider
      neurotoxin believed to cause massive release of vesicle-stored neurotransmitters,
      on spontaneously developed urethral smooth muscle tone. The effects were compared
      to those of EFS and high potassium. In the presence of the NO-synthesis inhibitor
      N(omega)-nitro-L-arginine (L-NOARG: 0.3 mM) both alphaLTX and EFS evoked
      contractions. After treatment with scopolamine and phentolamine, no contraction
      was observed, and under these conditions alphaLTX and EFS induced relaxation. At
      low frequencies (<12 Hz), the EFS-induced relaxations were rapid, whereas at
      higher frequencies (>12 Hz), they were biphasic, consisting of a rapid first
      phase followed by a more long-lasting second phase. L-NOARG abolished the
      relaxations at low frequencies, as well as the first phase of the biphasic
      relaxation. The second phase was not affected by treatment with L-NOARG, but 0.1
      microM omega-conotoxin GVIA, blocker of N-type voltage-operated calcium- channels
      (VOCCs), markedly reduced or abolished the response. In the presence of L-NOARG
      or omega-conotoxin GVIA, the alphaLTX-induced relaxation was significantly
      decreased, and the combination of L-NOARG and omega-conotoxin GVIA further
      reduced or abolished the relaxation. In preparations-treated with tetrodotoxin or
      scorpion venom, believed to inactivate nerves by acting on sodium channels,
      alphaLTX and EFS had no effects. alphaLTX-induced relaxation was not associated
      with changes in cyclic GMP or cyclic AMP content. High (80 mM) potassium solution
      induced a triphasic response of the preparation. A transient relaxation was
      followed by a restoration of tone, and then by a persistent relaxation. The
      persistent relaxation was slightly reduced by scorpion venom or L-NOARG, but
      reduced by 50% by a combination of L-NOARG and omega-conotoxin GVIA.
      Ultrastructural analysis of the urethral circular smooth muscle layer revealed a
      moderate amount of nerve profiles supplying the smooth muscle. In control
      preparations, the nerve profiles contained both small synaptic vesicles and large
      dense core vesicles. alphaLTX caused a major loss of both types of vesicle. The
      present data suggest that alphaLTX has the ability to release not only adrenergic
      and cholinergic transmitters, but also NANC mediators of relaxation, including
      NO, from nerve terminals in the urethra.

PMID- 9272720
TI  - Subtype determination of soma-dendritic alpha2-autoreceptors in slices of rat
      locus coeruleus.
AB  - The aim of the study was to subclassify the soma-dendritic alpha2-autoreceptors
      in the locus coeruleus (LC) of the rat by means of antagonists. To this end, the
      frequency of spontaneous action potentials was recorded extracellularly from
      single LC neurones in brain slices. The neurones fired spontaneously at an
      average rate of 1 Hz. The selective alpha2-adrenoceptor agonist 5-bromo-6-(2
      imidazolin-2-ylamino)-quinoxaline (UK 14,304) and noradrenaline decreased the
      action potential discharge with IC50 values of 5 and 510 nM, respectively. The
      concentration-inhibition curves of UK 14,304 and noradrenaline were shifted to
      the right by phentolamine (0.15 microM) and rauwolscine (0.15 microM) but not by
      prazosin (1 microM). Apparent Kd values of phentolamine were 17 nM (against UK
      14,304) and 20 nM (against noradrenaline). Apparent Kd values of rauwolscine were
      47 nM (against UK 14,304) and 70 nM (against noradrenaline). (+)-Oxaprotiline (1
      microM) suppressed the firing of the neurones within 10 to 33 min. In the
      continued presence of oxaprotiline, phentolamine and rauwolscine restored firing
      with EC50 values of 120 and 250 nM, respectively. Prazosin (1 microM) again was
      ineffective. All three antagonist affinity estimates - against UK 14,304,
      exogenous noradrenaline and endogenous noradrenaline (that accumulates in the
      extracellular space in the presence of oxaprotiline) - yield an affinity order
      phentolamine > rauwolscine >> prazosin, prazosin being ineffective even at a
      concentration of 1 microM. These findings identify the soma-dendritic alpha2
      autoreceptors of the LC as the rat variant of the alpha2A/D-adrenoceptor, i.e.
      alpha2D. Not only presynaptic but also soma-dendritic alpha2-autoreceptors may at
      least predominantly be alpha2A/D throughout the nervous system.

PMID- 9272721
TI  - Pontine reticular formation is involved in catalepsy produced by cholinergic
      drugs.
AB  - Bilateral kainic acid lesions of the ventro-medial (VM) thalamic nucleus of rats
      which greatly reduced the catalepsy produced by haloperidol (2 mg/kg i.p.) not
      only did not reduce, but even enhanced, the cataleptogenic effect of eserine (1
      mg/kg i.p.) and arecoline (30 mg/kg i.p.). This finding is in accord with former
      conclusions that catalepsy produced by cholinergic drugs does not depend on
      striatal mechanisms. In rats with kainic acid lesions of the VM thalamic nucleus,
      and similarly in intact, non-lesioned rats, systemic administration of eserine
      and arecoline potentiated the catalepsy produced by microinjections of carbachol
      (2 microg) into the pontine reticular formation (PRF). Atropine microinjected
      bilaterally into the PRF attenuated the cataleptogenic effect of eserine and
      arecoline i.p. We suggest that the PRF is a site at which systemically given
      cholinergic drugs act to produce catalepsy.

PMID- 9272722
TI  - Developmental differences in dopamine synthesis inhibition by (+/-)-7-OH-DPAT.
AB  - Dopamine synthesis modulation by the D2-family agonist (+/-)-7-OH-DPAT was
      explored in striatum, accumbens, and prefrontal cortex of 10-40 day old rats
      using the gamma-butyrolactone (GBL) autoreceptor model. GBL produced an age
      dependent increase in dopamine synthesis that was inhibited by (+/-) 7-OH-DPAT
      (0.1-13.5 mg/kg) at all ages and antagonized by eticlopride in the nucleus
      accumbens and striatum. The ID50 of (+/-) 7-OH-DPAT increased with age,
      suggesting decreased autoreceptor sensitivity with maturation. In prefrontal
      cortex, (+/-) 7-OH-DPAT inhibited synthesis between 10-30 days, with no evidence
      of autoreceptor function at 40 days. Dopamine synthesis was also inhibited with
      the D3/D2 agonist quinpirole at 15 days of age in vivo and yielded similar
      results to those obtained with (+/-) 7-OH-DPAT. Finally, under conditions that
      result in low D2 receptor affinity, D3 specificity was examined in vitro at 15
      days with (+/-) 7-OH-DPAT, which produced comparable (yet more potent) effects to
      those observed in vivo. These findings illustrate D3 autoreceptor-like activity
      in ascending dopamine regions and provide further support for transient
      prefrontal cortex autoreceptor-like function that recedes by puberty.

PMID- 9272723
TI  - MEN 11,420, a peptide tachykinin NK2 receptor antagonist, reduces motor responses
      induced by the intravesical administration of capsaicin in vivo.
AB  - This study investigates the role of tachykinin NK1 and NK2 receptors in motor
      responses induced by the intravesical instillation of capsaicin in urethane
      anaesthetized rats. SR 140,333 (1 micromol/kg, i.v.), a nonpeptide NK1 receptor
      antagonist, abolished urinary bladder contractions induced by the selective NK1
      receptor agonist [Sar9]SP-sulfone (0.1-100 nmol/kg, i.v.) without affecting those
      induced by the NK2 receptor agonist [betaAla8]NKA(4-10). MEN 11,420 (100 nmol/kg,
      i.v.), a cyclic peptide NK2 receptor antagonist, abolished bladder contractions
      induced by [betaAla8]NKA(4-10) (0.3-300 nmol/kg, i.v.) without modifying those
      induced by [Sar9]SP-sulfone. Intravesical instillation of capsaicin (6 nmol/0.6
      ml/rat) produced a motor response consisting in a primary contraction followed by
      a series of high amplitude phasic contractions. The intravesical instillation of
      saline (0.6 ml/rat) produced a primary contraction of lower amplitude with
      respect to that induced by capsaicin and the total area under the curve was also
      lower in saline-instilled rats, however the number and the amplitude of phasic
      contractions was similar to that induced by capsaicin. MEN 11,420 (100 nmol/kg,
      i.v.) did not modify motor responses induced by the intravesical administration
      of saline. In contrast, in capsaicin-instilled rats, MEN 11,420 (100 nmol/kg,
      i.v.) reduced the primary contraction, the area under the curve and also the
      number of phasic contractions. SR 140,333 (1 micromol/kg, i.v.) reduced the
      primary contraction but not other parameters. The combination of SR 140,333 (1
      micromol/kg, i.v.) and MEN 11,420 (100 nmol/kg, i.v.) produced an additive
      inhibitory effect on the primary contraction but not a further inhibition on
      other parameters with respect to that observed with MEN 11,420 alone. In
      hexamethonium (110 micromol/kg, i.v.)-pretreated animals the intravesical
      instillation of capsaicin produced a tonic contraction having greater amplitude
      and area than that induced by saline. MEN 11,420, but not SR 140,333,
      significantly reduced the bladder response to capsaicin in hexamethonium
      pretreated rats. Again, the combined administration of MEN 11,420 and SR 140,333
      did not produce further inhibitory effect in comparison to MEN 11,420 alone. It
      is concluded that the motor responses induced by the intravesical instillation of
      capsaicin are mediated by the activation of peripheral tachykinin NK2 receptors.

PMID- 9272724
TI  - A novel cognition enhancer NS-105 modulates adenylate cyclase activity through
      metabotropic glutamate receptors in primary neuronal culture.
AB  - The effect of (+)-5-oxo-D-prolinepiperidinamide monohydrate (NS-105), a novel
      cognition enhancer, on adenylate cyclase activity was investigated in cultured
      neurons of the mouse cerebral cortex. NS-105 (10(-7) and 10(-6) M) inhibited
      forskolin-stimulated cyclic AMP formation, an action that was dependent on
      pertussis toxin-sensitive G proteins. Conversely, in pertussis toxin-pretreated
      neurons, NS-105 (10(-7)-10(-5) M) significantly enhanced the forskolin-stimulated
      cyclic AMP formation, and this action was completely reversed by cholera toxin. A
      metabotropic glutamate receptor agonist (1S, 3R)-1-aminocyclopentane-1,3
      dicarboxylic acid (1S, 3R-ACPD) produced similar bi-directional actions on the
      cyclic AMP formation. Both of these inhibitory and facilitatory actions of NS-105
      and 1S, 3R-ACPD were blocked by L(+)-2-amino-3-phosphopropinoic acid (L-AP3). NS
      105 (10(-6) M) and 1S, 3R-ACPD (10(-4) M) significantly enhanced isoproterenol-
      and adenosine-stimulated cyclic AMP formation. The enhancement of such Gs-coupled
      receptor agonists-stimulated cyclic AMP formation was also produced by
      quisqualate but not by L(+)-2-amino-4-phosphonobutanoate (L-AP4). The
      phosphoinositides hydrolysis was enhanced by 1S, 3R-ACPD (10(-4) M) but not by NS
      105 (10(-6) M), however, 1S, 3R-ACPD-induced increase in phosphoinositides
      turnover was attenuated by NS-105. These findings suggest that NS-105 stimulates
      metabotropic glutamate receptor subclasses that are coupled both negatively and
      positively to adenylate cyclase, but it acts as an antagonist at the receptor
      subclasses that are linked to phosphoinositides hydrolysis.

PMID- 9272725
TI  - Cannabinoid CB1 receptor-mediated inhibition of the neurogenic vasopressor
      response in the pithed rat.
AB  - The effects of two cannabinoid receptor agonists, R(+)-[2,3-dihydro-5-methyl-3
      [(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4- benzoxazin-yl]-(1-naphthalenyl)
      methanone (WIN 55,212-2) and (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]
      trans-4-(3-hydr oxypropyl)-cyclohexanol (CP-55,940), were studied on (i) the
      vasopressor response elicited in pithed rats by electrical stimulation of the
      sympathetic outflow and (ii) the release of 3H-noradrenaline and the
      vasoconstriction elicited in isolated rat tail arteries by transmural electrical
      stimulation. In pithed rats, the electrical (1 Hz for 10 s) stimulation of the
      preganglionic sympathetic nerve fibres increased diastolic blood pressure by
      about 30 mmHg. This neurogenic vasopressor response (which under the conditions
      of our study was almost exclusively due to the release of catecholamines) was
      decreased by WIN 55-212,2 and CP-55,940 in a dose-dependent manner (inhibition by
      WIN 55,212-2 and CP-55,940, 0.1 micromol/kg each, about 25-30%). The inhibition
      was identical in adrenalectomized rats and in animals with intact adrenals. The
      inhibitory action of WIN 55,212-2 and CP-55,940 was abolished by a dose of 0.03
      micromol/kg of the CB1 receptor antagonist N-piperidino-5-(4-chlorophenyl)-1-(2,4
      dichlorophenyl)-4-methyl-3-pyrazo le-carboxamide (SR 141716), which, by itself,
      had no effect. WIN 55,212-2, CP-55,940 and SR 141716 failed to affect the
      vasopressor response to exogenous noradrenaline (1 nmol/kg), which also increased
      diastolic blood pressure by about 30 mmHg. In isolated rat tail arteries, the
      electrically (0.4 Hz) evoked tritium overflow and vasoconstriction were not
      modified by WIN 55,212-2 and CP-55,940 (1 micromol/l each). In conclusion, the
      neurogenic vasopressor response in the pithed rat can be modulated via
      cannabinoid CB1 receptors probably located presynaptically on the postganglionic
      sympathetic nerve fibres innervating resistance vessels.

PMID- 9272726
TI  - Ouabain improves cardiac function in vivo in rats with heart failure after
      chronic but not acute treatment.
AB  - Rats are generally believed to be insensitive for cardiac glycosides. However,
      like in humans, the hemodynamic effects may be related to the pathophysiological
      condition. Since the hemodynamic effects of cardiac glycosides have never been
      investigated in rats with heart failure, the aim of the present experiments was
      to investigate the role of the pathophysiological condition in the rat.
      Therefore, hemodynamic and cardiac effects of ouabain were investigated both in
      normal rats and rats with heart failure due to myocardial infarction (MI). Since
      the effects of ouabain may also depend on the treatment scheme, rats were treated
      either for a short-term period or a long-term period. Three weeks after sham
      surgery or ligation of the left coronary artery (MI), Wistar rats were treated
      for two weeks with ouabain (14.4 mg/kg.d s.c.), either continuously (osmotic
      minipumps) or intermittently (once daily). A separate group of rats was treated
      for 45-60 min (1-100 microg/kg.min ouabain; i.v. infusion 5 weeks after MI).
      Hemodynamic measurements were performed at rest and after volume loading in
      conscious rats, chronically instrumented with an electromagnetic flow probe and
      catheters. Induction of MI resulted in a significant increase in total peripheral
      resistance (TPR), and a significant decrease in basal and maximal cardiac output
      following volume loading (basal CO: sham, 92 +/- 5; MI, 74 +/- 5 ml/min; maximal
      CO: sham, 152 +/- 4; MI, 105 +/- 7 ml/min; n = 7-11). Chronic intermittent
      ouabain treatment further increased TPR in MI rats. In contrast, continuous
      ouabain treatment normalized TPR in rats. Only in continuously treated MI rats,
      basal and maximal CO improved significantly (basal: 83 +/- 4; maximal: 134 +/- 7
      ml/min; n = 7). Acute treatment dose-dependently worsened the hemodynamic
      conditions of MI rats, since TPR and MAP increased and CO and stroke volume
      decreased significantly. These experiments demonstrate that ouabain can improve
      cardiac function in rats, although only in MI rats and strongly depending on the
      delivery regimen. Thus, in contrast to the general belief, the presently used rat
      model is suitable for investigation of cardiac glycosides in heart failure. The
      preferential improvement of cardiac function in MI rats continuously treated with
      ouabain may depend upon changes in Na+,K+-ATPase or altered neurohumoral
      conditions due to MI and chronic treatment.

PMID- 9272727
TI  - Binding and effects of P1075, an opener of ATP-sensitive K+ channels, in the
      aorta from streptozotocin-treated diabetic rats.
AB  - Diabetes mellitus is associated with major vascular complications. It was the aim
      of this study to examine the function of the ATP-sensitive K+ channel (K(ATP)
      channel) in aortic rings prepared from diabetic rats and from age-matched
      controls. Diabetes was induced by injection of streptozotocin (60 mg/kg i.p.) and
      the animals were sacrificed 10 weeks after treatment. The binding of the K(ATP)
      channel opener, P1075 (N-cyano-N'-(1,1dimethylpropyl)-N"-3-pyridylguanidine), as
      well as the vasorelaxant and 86Rb+ efflux stimulating effects of the drug were
      measured. In endothelium-denuded rings from diabetic rats, the maximum
      contraction and sensitivity to noradrenaline were increased; in rings with intact
      endothelium, the acetylcholine-induced (endothelium-dependent) relaxation was
      similar in the two groups. In rings from diabetic rats the relaxation
      concentration curve of the K(ATP) channel opener P1075 against noradrenaline was
      shifted rightwards by a factor of 1.3 and the maximum relaxation was reduced from
      81 to 71% of initial tension (P <0.01). However, specific binding of 3H-P1075 was
      increased by 20% without a change in affinity, indicating that the number of
      binding sites for the opener was increased as a consequence of diabetes. In
      addition, P1075-induced 86Rb+ efflux, a qualitative measure of K(ATP) channel
      opening, was augmented by 50%. The data show that in the aorta from diabetic rats
      the K+ channel opening response to P1075 is markedly increased; however, the
      vasorelaxant effect to the K(ATP) channel opener is slightly impaired. A possible
      explanation of these findings is that the vasorelaxant mechanisms (which are in
      part independent of plasmalemmal K(ATP) channel opening) may be altered;
      alternatively, the link between membrane potential and smooth muscle tone may be
      changed in this model of insulin-dependent diabetes mellitus.

PMID- 9272728
TI  - G proteins endogenously expressed in Sf 9 cells: interactions with mammalian
      histamine receptors.
AB  - Expression of functionally active mammalian histamine H1- and H2-receptors was
      recently demonstrated in Sf 9 cells. Either receptor elicited phosphoinositide
      degradation leading to an increased cytoplasmic calcium concentration. In the
      present study we focussed on identifying the Sf 9 guanine nucleotide-binding
      proteins (G proteins) involved. Immunodetection of Sf 9 membranes showed
      expression of G alpha isoforms belonging to all four G protein subfamilies.
      During prolonged baculovirus infection of Sf 9 cells, binding of guanosine 5'-o
      (3-thiotriphosphate) as well as the intensities of G protein immunoreactivity,
      pertussis toxin-mediated ADP-ribosylation, GTP azidoanilide labelling of G alpha,
      and phosphate-labelling of G beta declined in cell membranes. Some 48 h after
      infection with mammalian histamine receptor-encoding viruses virtually no
      functional coupling of ligand-activated receptors to insect G proteins was
      observed despite a high level of expressed receptors. In contrast, Sf 9 cells
      infected only for 28 h allowed studies on histamine-induced G protein coupling.
      In membranes obtained from H1-receptor-expressing cells, histamine increased
      incorporation of GTP azidoanilide into Gq/11-like proteins whereas in membranes
      containing H2-receptors histamine enhanced GTP azidoanilide-labelling of Gq/11
      like and G(S)-like proteins. In fura-loaded H1- and H2-receptor-expressing cells
      histamine induced the release of calcium from intracellular stores. This study
      shows firstly that Sf 9 G proteins couple to mammalian histamine receptors and
      secondly that H1-receptors activate only Gq/11, whereas H2-receptors activate
      Gq/11 and G(S), but neither receptor couples to Gi/o or G12. Finally, the time
      following baculovirus infection is critical for studying the functional coupling
      between recombinantly expressed and endogenous signal transduction components.

PMID- 9272729
TI  - Alpha2-adrenoceptors in opossum kidney cells couple to stimulation of mitogen
      activated protein kinase independently of adenylyl cyclase inhibition.
AB  - We have compared the effects of adrenaline on activation of mitogen-activated
      protein kinase (MAP kinase), cyclic AMP accumulation and [3H]thymidine uptake in
      OK cells, a cell line derived from proximal tubules of the opossum kidney.
      Effects of serotonin and the direct protein kinase C activator, phorbol-12
      myristate-13-acetate (PMA), were also studied. Adrenaline transiently (peak at 5
      min, return to baseline by 30 min) and concentration-dependently (EC50 between 10
      and 100 nM) stimulated MAP kinase activity. Maximal stimulation was approximately
      100% above basal and was similar to the effects of 1 microM serotonin or 1 microM
      PMA. MAP kinase activation by adrenaline was inhibited by 10 microM phentolamine
      or 1 microM yohimbine but not significantly affected by 100 nM prazosin or 200 nM
      pindolol. The selective alpha2-adrenoceptor agonist UK 14,304 (10 microM) also
      stimulated MAP kinase activity. Activation of the 42 and 44 kDa ERK forms of MAP
      kinase was demonstrated by immunoblot analysis. The effect of adrenaline and UK
      14,304 on MAP kinase was inhibited by pertussis toxin pretreatment and by the MAP
      kinase kinase inhibitor, PD 98059 (100 microM). Stimulation of MAP kinase
      activity was independent of cellular cAMP levels and was not affected by protein
      kinase C downregulation. Adrenaline, UK 14,304, serotonin, and PMA stimulated
      [3H]thymidine uptake, an effect inhibited by PD 98059. We conclude that
      adrenaline stimulates MAP kinase activity in OK-cells via alpha2-adrenoceptors
      and pertussis sensitive G proteins. While this occurs independently of cellular
      cAMP levels and protein kinase C, it involves the MEKI form of MAP kinase kinase
      and the ERK forms of MAP kinase. This activation results in enhanced cellular
      proliferation as assessed by [3H]thymidine uptake.

PMID- 9272730
TI  - Pharmacological properties of Ca2+-activated K+ currents of ramified murine brain
      macrophages.
AB  - Using the whole-cell configuration of the patch clamp technique, calcium
      activated potassium currents (I(K,Ca)) were investigated in ramified murine brain
      macrophages. In order to induce I(K,Ca) the intracellular concentration of
      nominal free Ca2+ was adjusted to 1 microM. The Ca2+-activated K+ current of
      brain macrophages did not show any voltage dependence at test potentials between 
      120 and +30 mV. A tenfold change in extracellular K+ concentration shifted the
      reversal potential of I(K,Ca) by 51 mV. The bee venom toxin apamin applied at
      concentrations of up to 1 microM did not affect I(K,Ca). Ca2+-activated K+
      currents of ramified brain macrophages were highly sensitive to extracellularly
      applied charybdotoxin (CTX). The half-maximal effective concentration of CTX was
      calculated to be 4.3 nM. In contrast to CTX, the scorpion toxin kaliotoxin did
      not inhibit I(K,Ca) at concentrations between 1 and 50 nM. Tetraethylammonium
      (TEA) blocked 8.0% of I(K,Ca) at a concentration of 1 mM, whereas 31.4% of
      current was blocked by 10 mM TEA. Several inorganic polyvalent cations were
      tested at a concentration of 2 mM for their ability to block I(K,Ca). La3+
      reduced I(K,Ca) by 72.8%, whereas Cd2+ decreased I(K,Ca) by 17.4%; in contrast,
      Ni2+ did not have any effect on I(K,Ca). Ba2+ applied at a concentration of 1 mM
      reduced I(K,Ca) voltage-dependently at hyperpolarizing potentials.

PMID- 9272731
TI  - Mechanisms of serotonin-induced Ca2+ responses in mesangial cells.
AB  - Smooth muscle cell-like mesangial cells play an important role in the regulation
      of glomerular blood flow and are involved in renal inflammatory reactions,
      thereby interacting with circulating cells. The platelet products serotonin (5
      HT) and ATP induce similar, e.g. mitogenic, effects in mesangial cells, but
      differentially activate and induce inflammation-related genes. To get an insight
      into intracellular signaling steps, a very early step in the signaling cascade,
      the biphasic Ca2+ signal elicited by 5-HT and ATP in rat mesangial cells was
      investigated. Both phases of the Ca2+ signal, release from internal stores as
      well as influx of extracellular Ca2+, were dependent on phospholipase C
      activation as shown by the specific inhibitor U73122 (complete inhibition at 10
      microM U73122). There was no evidence for voltage-gated L-type channels in these
      cells, suggesting that Ca2+ influx was mediated by Ca2+ release-activated
      channels. The L-type channel blocker verapamil, however, dose-dependently (0.1-10
      microM) and specifically inhibited 5-HT-elicited Ca2+ signals by interference
      with binding of 5-HT to 5-HT2A receptors. 5-HT-mediated Ca2+ release was reduced
      by 80% when protein kinase C was activated by the phorbolester TPA (0.1 microM).
      Interaction of 5-HT2A receptors with phospholipase C was also inhibited by
      genistein (30% at 5 microM; 100% at 50 microM), an inhibitor of tyrosine kinases.
      Binding of 5-HT to its receptor reduced subsequent ATP-mediated Ca2+ signaling.
      The cross talk between the receptors was sensitive to genistein. ATP-mediated
      Ca2+ signaling was attributed to different types of P2y receptors and/or multiple
      G-proteins coupled, because the signal was partially inhibited by pertussis toxin
      (50%). In accordance, modulation of the ATP-mediated signaling by phosphorylation
      was less tightly controlled than 5-HT-mediated Ca2+ release. These data indicate
      that although the Ca2+ responses elicited by the two stimuli are comparable,
      interactions between receptors, G-proteins and target enzymes are regulated
      differentially.

PMID- 9272732
TI  - Characterisation of pre- and post-synaptic alpha-adrenoceptors in modulation of
      the rat ileum longitudinal and circular muscle activities.
AB  - Previous study has shown that alpha2D-adrenoceptors are involved in modulation of
      peristalsis in the rat ileum. The aim of the present study was to determine the
      tissue location of alpha-adrenoceptors in the rat ileum by using a recently
      devised method. The pre-synaptic alpha-adrenoceptors were characterised by
      measuring the potencies of agonists to inhibit transmurally-evoked (1 ms pulses,
      10 Hz, 8-10 s trains) contractions of the longitudinal and circular muscles and
      the affinities of antagonists. Post synaptic alpha-adrenoceptors were identified
      by screening agonists and antagonists in carbachol-contracted tissues. In the
      circular muscle the order of potencies for inhibiting transmurally-induced
      contraction was: clonidine > or = oxymetazoline > or = UK 14,304 > or =
      guanfacine > talipexole > phenylephrine > azepexole. The potency ratios relative
      to clonidine correlated to those previously derived using the rat ileum
      peristaltic reflex preparation. Most of the alpha-adrenoceptor agonists, however,
      caused only small inhibitions of the longitudinal muscle contraction in response
      to transmural stimulation, except phenylephrine and azepexole. RX 821002,
      yohimbine, rauwolscine, BRL 44408, phentolamine, idazoxan, ARC 239, and prazosin
      inhibited the effect of clonidine on the circular muscle response with apparent
      pK(B) values best correlated with pK(B) or pKi values derived from the rat ileum
      peristaltic reflex preparation and other tissues known to have the alpha2D
      subtype. The rank order of potencies at inhibiting carbachol-induced responses of
      both muscle layers was: phenylephrine > or = oxymetazoline > clonidine > or =
      talipexole > azepexole >> guanfacine. UK 14,304 was inactive up to 10 microM. The
      EC50 value of each agonist on the longitudinal muscle was not significantly
      different to the corresponding value on the circular muscle. Prazosin was more
      potent than yohimbine at inhibiting the relaxant effect of phenylephrine in both
      muscle layers of carbachol-contracted tissues. It is concluded that the recently
      identified alpha2D-adrenoceptors of the rat ileum are located on cholinergic
      neurons controlling circular muscle contraction. The study also demonstrated the
      presence of postsynaptic alpha1-adrenoceptors involved in mediating relaxation in
      both muscle layers.

PMID- 9272733
TI  - The transformation of irinotecan (CPT-11) to its active metabolite SN-38 by human
      liver microsomes. Differential hydrolysis for the lactone and carboxylate forms.
AB  - Irinotecan (CPT-11) is a new camptothecine derivative presently in development
      for the treatment of several advanced malignancies. It is converted in vivo to a
      highly potent metabolite, SN-38, by carboxylesterases. All camptothecine
      derivatives undergo lactonolysis in a pH-dependent reversible manner, generating
      inactive carboxylate forms. We have investigated in vitro the kinetics of
      transformation of CPT-11 to SN-38 by human liver microsomes originating from
      several donors. Microsomes from seven livers were studied individually or as a
      pooled preparation. CPT-11, either in its lactone or its carboxylate form, was
      added at a range of concentrations. The SN-38 formed was measured by HPLC with
      fluorometric detection. In the deacylation-limited carboxylesterase reaction, the
      linear steady-state kinetics between 10 and 60 min were determined. At all
      concentrations of CPT-11, the steady-state velocity of SN-38 formation as well as
      the intercept concentrations of SN-38 were about 2-fold higher when the substrate
      was under the lactone form than under the carboxylate form. We estimated the
      values (+/-SD) of K'm and Vmax to be 23.3 +/- 5.3 microM and 1.43 +/- 0.15
      pmol/min/mg for the lactone and 48.9 +/- 5.5 microM and 1.09 +/- 0.06 pmol/min/mg
      for the carboxylate form of CPT-11, respectively. We conclude that the greater
      rate of conversion of CPT-11 lactone may contribute to the plasma predominance of
      SN-38 lactone observed in vivo. The inter-individual variation of SN-38 formation
      was relatively high (ratio of 4 between extreme values) but no large age- or
      gender-related differences were seen. The effect of twelve drugs of different
      therapeutic classes (antibiotics, antiemetics, antineoplastics, antidiarrhoeics,
      analgesics), which could be administered in association with irinotecan in the
      clinical setting, was evaluated in this system (drug concentration: 100 microM;
      CPT-11 lactone concentration: 10 microM). Loperamide and ciprofloxacine where the
      only drugs exerting a weak inhibition of CPT-11 conversion to SN-38.

PMID- 9272734
TI  - The beta3-adrenoceptor agonist SR58611A inhibits gastric acid secretion in the
      conscious cat.
AB  - The effect of the beta3-adrenoceptor agonist [ N-[(2S)-7-ethoxycarbonyl-methoxyl
      1,2,3,4-tetrahydronaphth-2-yl] (2R)-2-(3-chloro-phenyl)2-hydroxyethanamine
      hydrochloride] (SR58611A) on gastric acid secretion was investigated in conscious
      cats with a gastric fistula. Intravenous infusion of SR58611A (0.3-3
      micromol/kg/h) caused a dose-dependent inhibition of the acid secretion
      stimulated by 2-deoxy-D-glucose (2DG), with a maximum reduction by 45%. The
      secretory effect of the histamine H2-receptor agonist dimaprit only tended to be
      reduced by SR58611A (3 micromol/kg/h). The inhibitory effect of SR5861 IA was not
      modified by the non selective beta1- and beta2-adrenoceptor antagonist
      propranolol (1.5 micromol/kg i.v.), but it was prevented by bupranolol (10
      micromol/kg i.v.), a drug endowed with beta3-antagonistic properties. Both
      antagonists blocked the inhibitory effect of the beta2-adrenoceptor agonist
      clenbuterol (0.1 micromol/kg/h) on 2DG-induced acid secretion. These findings
      suggest that compound SR58611A inhibits gastric acid secretion in the conscious
      cat through activation of beta3-adrenoceptors insensitive to propranolol.

PMID- 9272735
TI  - Human and clinical cytogenetics: origins, evolution and impact.

PMID- 9272736
TI  - A chronic GM2 gangliosidosis variant with a HEXA splicing defect: quantitation of
      HEXA mRNAs in normal and mutant fibroblasts.
AB  - Over 72 mutations have been identified in the HEXA gene of which only four
      (T538C, A590C, G805A, and C1495T) are believed to cause a chronic form of Tay
      Sachs disease (TSD). We identified a novel HEXA mutation (IVS7, -7 G-->A) leading
      to chronic TSD in a Canadian patient of English ancestry. The second allele in
      this patient was the exon 11 4-bp insertion mutation (/1277TATC), which is the
      most frequent TSD allele in Ashkenazi Jews. The IVS7, -7 G-->A mutation
      introduces a new 3' splice acceptor site 5 bp upstream of the normal intron 7
      splice acceptor site. The mutation leads to reduction of steady-state levels of
      HEXA mRNA by more than 80%. Two mRNA species are produced by the IVS7, -7 G-->A
      allele; a normal nRNA species and an mRNA lacking exon 8. No mRNA species that
      was spliced at the upstream 3' splice acceptor site was detected. We used
      competitive PCR to quantitate mRNA species in fibroblasts obtained from this
      patient. We compared the amounts of three identified mRNA species to HEXA mRNA
      levels in cells from normal individuals and from individuals heterozygous for
      /1277TATC. The steady-state level of HEXA mRNA in cells from a normal individual
      was 17.3 pg/microg RNA. An individual heterozygous for /1277TATC produced 8.7 pg
      of normal HEXA mRNA/microg RNA. The HEXA mRNA species with the insertion mutation
      was present in patient cells at 4.8% of the level of normal HEXA nRNA in
      homozygous normal cells. In fibroblasts from the patient carrying the IVS7, -7 G-
      >A mutation, the steady-state level of exon 8-deleted HEXA mRNA was 5.9% the
      level of that produced by homozygous normal cells. The level of normal HEXA nRNA
      in this patient's cells was 10.4%.

PMID- 9272737
TI  - Somatic mosaicism in Fanconi anemia: molecular basis and clinical significance.
AB  - Approximately 25% of patients with Fanconi anemia (FA) have evidence of
      spontaneously occurring mosaicism as manifest by the presence of two
      subpopulations of lymphocytes, one of which is hypersensitive to cross-linking
      agents (e.g. mitomycin C) while the other behaves normally in response to these
      agents. The molecular basis of this phenotypic reversion has not yet been
      determined. We have investigated 8 FA patients with evidence of mosaicism.
      Epstein-Barr virus-immortalized lymphoblastoid cell lines established from these
      patients exhibited an IC50 for mitomycin C of 25 to > 100 nM compared to a mean
      of 2 +/- 2 nM for 20 nonmosaic FA patients and 49 +/- 11 nM for 8 healthy
      controls. In 3 patients who were compound heterozygotes for pathogenic FAC gene
      mutations the molecular mechanism of the mosaicism was investigated by haplotype
      analysis. The results indicated that an intragenic mitotic recombination must
      have occurred leading to a segregation of a wild-type allele in the reverted
      cells and suggested two patterns of recombination. In 1 patient a single
      intragenic crossover between the maternally and paternally inherited mutations
      occurred associated with markers located distally to the FAC gene; in the other 2
      patients (sibs) the mechanism appears to have been gene conversion resulting in
      segregants which have lost one pathogenic mutation. In 6 of the 8 patients the
      hematological symptoms were relatively mild despite an age range of 9-30 years.

PMID- 9272738
TI  - CFTR gene mutations in adults with disseminated bronchiectasis.
AB  - The severity and type of clinical manifestations are variable in patients with
      cystic fibrosis (CF). The respiratory syndromes in these patients consist of lung
      infections associated with disseminated bronchiectasis (DB), asthma, and chronic
      obstructive pulmonary disease. To investigate the possible involvement of the
      cystic fibrosis transmembrane conductance regulator (CFTR) gene in chronic
      pulmonary disease in adults, we studied 32 DB patients with a clinically isolated
      respiratory syndrome. Careful analysis of all the CFTR gene exons and their
      flanking regions revealed a significantly increased frequency of CFTR gene
      mutations in these patients. Thirteen CFTR gene mutations were identified in
      sixteen different alleles. Six of these mutations, which have previously been
      reported as CF defects, were found on nine alleles. A further four, two of which
      had not previously been described (D192N and 406-2 AdeltaC), are potentially
      disease-causing mutations. We also identified three rare substitutions (R31C,
      L997F, T1220I), which could be involved in mild CFTR gene disease. Four patients
      were compound heterozygotes, one carried two CFTR gene mutations (possibly
      allelic) and six were heterozygous for a mutation. These results indicate that
      CFTR gene mutations may play a role in bronchiectatic lung disease, possibly in a
      multifactorial context. These findings have implications for genetic counselling
      of DB patients and their families.

PMID- 9272739
TI  - Mapping of Papillon-Lefevre syndrome to the chromosome 11q14 region.
AB  - Papillon-Lefevre syndrome (PLS) is an autosomal recessive disease which belongs
      to the palmo-plantar keratoderma (PPK) group. It is characterized by a premature
      loss of primary and permanent teeth and early onset periodontitis. High
      consanguinity has been observed in over one-third of PLS families. No candidate
      genes or gene localizations have been described to date for this disorder. A
      primary genome-wide search by homozygosity mapping using samples from a large
      consanguineous family in which 4 siblings were affected by the disease showed
      homozygosity and linkage in the region of 11q14. Linkage was confirmed in 4
      additional families with diverse ethnic and geographic backgrounds, 2 of which
      were consanguineous. A maximum two-point lod score of 8.19 was obtained for the
      marker AFM063yg1 (D11S901= for theta = 0. Analysis of recombination events places
      the gene within a 7-cM interval between AFM063yg1 and AFM269yg9 (D11S4175). No
      shared haplotype was found for the 5 families analysed.

PMID- 9272740
TI  - Osteogenesis imperfecta phenotypes resulting from serine for glycine
      substitutions in the alpha2(I) collagen chain.
AB  - Clinical and biochemical findings in 5 unrelated patients with osteogenesis
      imperfecta (OI) with a serine for glycine substitution in the alpha2(I) collagen
      chain are presented. The data are compared to other serine substitutions in
      collagen type I. Findings show that the phenotypic severity of serine for glycine
      substitutions in the alpha2(I) collagen chain is region dependent similar to the
      observations for the alpha1(I) collagen chain, and that so-called 'lethal' and
      'non-lethal' domains in the alpha1 and alpha2 collagen chains do not necessarily
      correspond.

PMID- 9272741
TI  - Linkage analysis in 16 families with incontinentia pigmenti.
AB  - A locus for the X-linked dominant genodermatosis incontinentia pigmenti (IP) has
      been linked to markers in Xq28. Here we report high lod scores for markers
      spanning the interval DXS52-DXYS154 using 16 families, providing further evidence
      for a single major X-linked IP locus.

PMID- 9272743
TI  - Tetrasomy 18p caused by paternal meiotic nondisjunction.

PMID- 9272742
TI  - A YAC contig spanning the blepharophimosis-ptosis-epicanthus inversus syndrome
      and propionic acidemia loci.
AB  - Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is an autosomal
      dominant condition consisting of congenital dysplasia of the eyelids with a
      reduced horizontal diameter of the palpebral fissures, droopy eyelids and
      epicanthus inversus. Two clinical entities have been described: type I and type
      II. The former is distinguished by female infertility, whereas the latter
      presents without other symptoms. Both type I and type II were recently mapped on
      the long arm of chromosome 3 (3q22-q23), suggesting a common gene may be
      affected. The centromeric and the telomeric limits of this region are well
      defined between loci D3S1316 and D3S1615, which reside approximately 5 cM apart.
      Here, we present the construction of a YAC contig spanning the entire BPES locus
      using 17 polymorphic markers, 2 STS and 28 ESTs. This region of approximately 5
      Mb was covered by 31 YACs, and was supported by detailed FISH analysis. In
      addition, we have precisely mapped the propionyl-CoA carboxylase beta polypeptide
      (PCCB), the gene mutated in propionic acidemia, within this contig. Apart from
      providing a framework for the identification of the BPES gene, this contig will
      also be useful for the future identification of defects and genes mapped to this
      region, and for developing template resources for genomic sequencing.

PMID- 9272744
TI  - Auditory and tactile bone-conduction thresholds using three different
      oscillators.
AB  - Determination of tactile bone-conduction (BC) thresholds is essential to provide
      proper diagnosis of individuals with profound hearing loss. In this study,
      auditory and tactile BC thresholds were compared using three oscillators: the
      Radioear B-70-A, B-71, and B-72 with mastoid and forehead placement. Subjects
      included 12 adults with normal hearing (to establish auditory thresholds) and 12
      adults with profound sensorineural hearing loss (to establish tactile
      thresholds). All 24 subjects were tested at octave intervals from 250 through
      4000 Hz. As demonstrated in previous studies, tactile thresholds were lower for
      the low frequencies. Some differences in tactile thresholds were evinced as a
      function of different oscillators. One fact that emerged from this study is the
      lower tactile threshold with forehead placement as compared to the mastoid. While
      ostensibly a disadvantage to forehead BC testing, there are some clinical
      advantages to be gleaned from this discovery.

PMID- 9272745
TI  - Screening infants and young children for hearing loss: examination of the CAST
      procedure.
AB  - A computer-mediated visual reinforcement audiometry (VRA) screening procedure,
      the Classification of Audiograms by Sequential Testing (CAST), was used with 59
      infants and young children who received both CAST screening and conventional
      audiologic assessment. Approximately one-third of the children had normal
      hearing, one-third had conductive hearing loss, and the remaining one-third had
      previously diagnosed sensorineural hearing loss. The sensitivity and specificity
      of CAST were calculated and the relationship between the predicted CAST pattern
      and the child's actual audiogram was examined. CAST outcome was also considered
      along with the results of tympanometry and pneumatic otoscopy to formulate
      proposed follow-up strategies. CAST appears to be a useful tool for the
      behavioral screening of infants and young children: one component of a screening
      program designed to maximize the efficient identification and follow-up of
      infants and children with hearing loss.

PMID- 9272746
TI  - IHAFF loudness contour test: reliability and effects of approach mode in normal
      hearing subjects.
AB  - This study investigated the effects of approach mode (ascending, descending,
      random) on the normal loudness function using the Loudness Contour Test suggested
      by the Independent Hearing Aid Fitting Forum. We also assessed how increasing the
      number of trials from one to five affects the short-term reliability of the
      Loudness Contour Test. Additionally, we examined the relationship between
      loudness judgments (very soft to uncomfortably loud) for warble tones and
      loudness judgments for speech. Thirty-one normal-hearing subjects were tested
      using 500-Hz and 3000-Hz tones and speech (CID W-22 words preceded by a carrier
      phrase). The results revealed that 5- to 12-dB higher SPLs were found with the
      descending approach than with the ascending approach. The reliability results
      suggest that it is not beneficial to present more than one or two trials when
      administering the Loudness Contour Test. The true sound pressure level (SPL) for
      a given loudness category will fall within +/-10 to 12 dB of the obtained SPL
      approximately 95 percent of the time. This 20- to 24-dB range is fairly large and
      it is questionable whether reliability is sufficient to justify obtaining
      individual loudness measurements. When the relationship between warble tones and
      speech was investigated, the results revealed an overall standard error of
      estimate of approximately 8 dB. These data suggest that warble tones are not
      accurate predictors of the corresponding loudness categories for speech. If the
      clinician wants to ascertain SPLs that correspond to the various loudness
      categories for speech, then direct measurement with a speech stimulus appears
      necessary.

PMID- 9272747
TI  - Effectiveness of three central auditory processing (CAP) tests in identifying
      cerebral lesions.
AB  - The effectiveness of three central auditory processing (CAP) tests was evaluated
      using clinical decision analysis (CDA) procedures. The tests under study were the
      Dichotic Digits Test (DDT), the Auditory Duration Patterns Test (ADPT), and the
      P300 evoked potential test (P300). Subjects with normal hearing, sensorineural
      hearing loss (SNHL), and central lesions provided the data for CDA analyses. To
      identify the most effective test, we used the conventional CDA parameters of hit
      rate (sensitivity), false-positive rate (1 - false-positive rate = specificity),
      and A' (test performance at specific hit/false-positive combinations). Further,
      we illustrated the extension of the conventional CDA parameters to posterior
      probability determination, which incorporates disorder prevalence to compute the
      likelihood of a patient having a disorder when a test result is positive
      (Pr[D/+]) or not having a disorder when the test result is negative (Pr[N/-]).
      Last, we used the CDA parameter of hit rate and disorder prevalence to determine
      cost effectiveness.

PMID- 9272748
TI  - Persistent pulmonary hypertension of the newborn (PPHN) treated with inhaled
      nitric oxide: preliminary hearing outcomes.
AB  - The hearing of 28 children, born with a diagnosis of persistent pulmonary
      hypertension of the newborn (PPHN) and treated with inhaled nitric oxide, was
      followed. The latest test for the children varied from 5 to 30 months. Of this
      group, three children had mild conductive hearing losses; no child had a
      significant sensorineural hearing loss.

PMID- 9272749
TI  - Factor analytic structure of auditory impairment in elderly persons.
AB  - The audiometric and self-assessed handicap data of 180 elderly persons with
      presbyacusic-type hearing impairment were submitted to principal components
      analysis in order to study the factor structure underlying auditory processing.
      Audiometric data included pure-tone threshold sensitivity, speech understanding
      scores for monosyllabic words without competition, synthetic sentences within
      competition, and dichotic synthetic sentence identification. The Hearing Handicap
      Inventory for the Elderly (HHIE) was used to quantify self-assessed handicap both
      by the subjects and by their significant others. Six factors emerged from the
      analysis: (1) low-frequency sensitivity loss, (2) high-frequency sensitivity
      loss, (3) general speech understanding ability, (4) self-assessed handicap, (5)
      the central processing of left ear input, and (6) the central processing of right
      ear input. Five conclusions are highlighted: (1) degree of hearing sensitivity
      loss, which determines speech audibility, remains a key concept in understanding
      the speech understanding problems of elderly persons; (2) low-frequency and high
      frequency sensitivity loss emerge as separate factors; (3) a factor of general
      speech understanding ability, not strongly related to audibility, is confirmed;
      (4) the central processing of right and left ear verbal inputs emerge as separate
      factors; and (5) perceived auditory handicap emerges as a separate factor,
      apparently not strongly related to either audibility, general speech
      understanding, or the central processing of verbal input.

PMID- 9272750
TI  - Valsalva shift among smokers and nonsmokers.
AB  - Although it has been reported that smoking has deleterious effects on the middle
      ears of smokers, including their eustachian tubes, investigators have failed to
      find differences in the tympanometric characteristics of smokers and nonsmokers.
      In the present study, however, we found that the Valsalva-induced tympanometric
      peak pressure shifts of young smokers were less than those measured among young
      nonsmokers. A similar but less compelling finding was observed among elderly
      subjects.

PMID- 9272751
TI  - Differences in performance between Oticon MultiFocus Compact and ReSound BT2-E
      hearing aids.
AB  - Differences in performance were evaluated between binaural fittings of the Oticon
      MultiFocus (MF) and ReSound BT2-E on 25 hearing-impaired subjects across two
      sites. Subjects were initially fit using each manufacturer's algorithm and
      adjustments were made at 1 week based on subjects' responses to diary questions.
      Performance was assessed after a 4- to 6-week trial period with each hearing aid
      set using the Speech Perception in Noise (SPIN) test administered at 50, 65, and
      80 dB SPL, the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire,
      loudness judgments of female connected discourse at 65 and 80 dB SPL, and an
      overall preference selection. The MF yielded significantly better SPIN scores at
      50 and 65 dB SPL, while the BT2-E yielded a significantly better score at 80 dB
      SPL. No statistically significant differences were found in the APHAB benefit
      scores between the hearing aid sets, but both sets were significantly better than
      the subjects' own hearing aids on three of the four subscales. The MF produced
      slightly higher mean loudness judgments at both input levels than the BT2-E.
      Finally, 12 subjects preferred the BT2-E, 10 subjects preferred the MF, and three
      subjects stated no preference. The results are discussed in terms of audiogram
      effects on preference and effects of differences in signal processing approaches
      between the devices.

PMID- 9272752
TI  - Rewarding properties of gamma-hydroxybutyric acid: an evaluation through place
      preference paradigm.
AB  - Gamma-hydroxybutyric acid (GHB), a putative neurotransmitter or neuromodulator
      found in the mammalian brain, has been successfully used in clinical practice to
      alleviate both alcohol and opiate withdrawal symptoms. In the present study we
      used a conditioned place preference (CPP) paradigm to investigate whether GHB
      possesses rewarding properties in rats. In order to exclude possible artifacts
      due to experimental design, we evaluated the possibility of a shift in preference
      when rats are conditioned either on their non-preferred side or on a randomly
      assigned side of conditioning. In both experiments GHB was seen to induce CPP.
      Although to date the physiological role of this compound still remains unclear,
      there is no doubt that GHB, further to its proven effect on alcohol and opiates,
      possesses rewarding properties of its own. The abuse liability afforded by this
      drug suggests the use of particular caution in handling GHB as a clinically
      useful drug.

PMID- 9272753
TI  - Anxiolytic activity of NPY receptor agonists in the conflict test.
AB  - This investigation examined receptor subtype specificity and possible modulation
      by GABAa receptor ligands of NPY-induced behavioral responses to stressful
      stimuli. First, a series of NPY receptor agonists were examined for their
      potential effects on punished responding in a conflict test modified for
      incremental shock. NPY, peptide YY (PYY) and NPY Y1 receptor agonists
      [Leu31,Pro34]-NPY and [Gly6, Glu26,Lys26,Pro34]-NPY produced increases in
      punished responding in the conflict test. No significant effects on unpunished
      responding were noted. The pattern of responding was similar to that observed
      with the benzodiazepine agonist chlordiazepoxide. Neither pancreatic peptide (PP)
      nor the Y2 agonists NPY13-36 or [Glu2,32,Ala6,Dpr27,Lys28]-NPY significantly
      altered punished or unpunished responding. Of significance, the atypical Y1
      agonist [Cys7,21,Pro34]-NPY produced negligible effects on punished responding,
      consistent with the presence of a subclass of Y1 receptors. Second, the
      anxiolytic effects of NPY were subjected to treatments that block actions at the
      GABAa receptor complex. The increase in punished responding produced by NPY was
      not altered by administration of the benzodiazepine antagonist flumazenil and
      only partially blocked by the picrotoxinin receptor ligand
      isopropylbicyclophosphate (10 and 15 microg/kg). These findings further support
      the hypothesis that the pharmacologic substrates for the anxiolytic-like actions
      of NPY may be mediated by the Y1 receptor subtype and suggest that these actions
      are independent of either the benzodiazepine or picrotoxinin binding sites of the
      GABA/benzodiazepine receptor complex.

PMID- 9272754
TI  - Antagonism of non-NMDA receptors in the dorsal periaqueductal grey induces
      anxiolytic effect in the elevated plus maze.
AB  - Microinjections of glutamate into the dorsal periaqueductal grey (DPAG) of rats
      induce flight behavior, and blockade of glutamate NMDA receptors in the same
      region increases exploratory behavior of rats tested on the elevated plus maze.
      To investigate a possible role of other glutamate receptors in the DPAG on
      anxiety modulation, rats (n = 6-10) received microinjections into this structure
      of CNQX (1 and 3 nmol/0.5 microl), an AMPA/kainate antagonist, or GDEE (80 or 160
      nmol/0.5 microl), a non-selective glutamate antagonist, and were tested on the
      elevated plus-maze, an ethologically based animal model of anxiety. Both drugs
      increased the percentage of entries into open arms, as compared to rats receiving
      vehicle, without changing the number of enclosed arm entries. Injections of the
      active compounds outside the DPAG were not effective. The anxiolytic effect of
      CNQX (3 nmol/0.5 microl) was not reversed by glycine (10 nmol/0.5 microl),
      injected into the DPAG 5 min after CNQX administration. These results suggest
      that, in addition to NMDA receptors, non-NMDA glutamate receptors may also
      modulate anxiety in the DPAG.

PMID- 9272755
TI  - Serotonin1A receptor autoradiography during alcohol-withdrawal kindling.
AB  - A series of autoradiography experiments were conducted in order to test the
      theory that the serotonin (5-HT) receptor subtype 5-HT(1a) is involved in alcohol
      withdrawal kindled convulsive behaviour. Alcohol-withdrawal kindling was
      performed by subjecting male Wistar rats to multiple episodes consisting of 2
      days of alcohol intoxication and 5 days of alcohol withdrawal. In the first
      episode alcohol intoxication led to focal downregulation of [3H]-8-hydroxy-2-(di
      n-propylamino)tetralin ([3H]-8-OH-DPAT) binding sites in septum and subregions of
      frontal cortex, hippocampus, and entorhinal cortex. This alcohol-induced response
      was blunted in both alcohol-withdrawal kindled animals and in animals exposed to
      repeated alcohol dependence in which the previous withdrawal reactions were
      blocked by diazepam administration. A paradoxical upregulation of [3H]-8-OH-DPAT
      binding sites was found in septum and subregions of frontal cortex, hippocampus,
      and entorhinal cortex in control animals which were fed isocalorically with the
      alcohol-withdrawal kindled animals and subsequently exposed to 2 days of alcohol
      intoxication. It was concluded that the alterations in the alcohol induced 5
      HT(1a) receptor regulation after multiple episodes of alcohol dependence were not
      caused by alcohol-withdrawal kindling processes per se, but were due to both
      alcohol specific and alcohol non-specific effects.

PMID- 9272756
TI  - Serotonergic modulation of the discriminative-stimulus effects of cocaine in
      squirrel monkeys.
AB  - In order to investigate the potential modulatory role of serotonin on the
      discriminative-stimulus effects of cocaine, two groups of squirrel monkeys were
      trained to discriminate 0.3 mg/kg or 1.0 mg/kg cocaine and saline under a two
      lever drug-discrimination procedure. Substitution of a range of cocaine doses
      (0.03-1.7 mg/kg) occasioned orderly, dose-dependent increases in cocaine-lever
      responding. When administered alone, the non-selective serotonin direct agonist,
      quipazine, also occasioned increases in cocaine-lever responding which were more
      pronounced in subjects trained with the lower cocaine dose. When quipazine was
      administered in combination with cocaine, there was an increase in cocaine-lever
      responding, indicating an additive effect. The serotonin uptake inhibitor,
      fluoxetine, occasioned saline-lever responding when administered alone. However,
      in combination with cocaine, fluoxetine enhanced the discriminative effects of
      cocaine in subjects trained at the lower cocaine dose. The 5-HT2-selective
      antagonists, ketanserin and ritanserin, did not occasion cocaine-lever responding
      when administered alone. In combination with cocaine, ketanserin attenuated the
      discriminative effects of cocaine in most subjects, and ritanserin attenuated the
      discriminative effects of cocaine in subjects trained at the higher dose. These
      results indicate that the discriminative-stimulus effects of cocaine may be
      increased by direct- and indirect-acting serotonin agonists and attenuated by
      serotonin antagonists in squirrel monkeys.

PMID- 9272757
TI  - On the elevated plus-maze the anxiolytic-like effects of the 5-HT(1A) agonist, 8
      OH-DPAT, but not the anxiogenic-like effects of the 5-HT(1A) partial agonist,
      buspirone, are blocked by the 5-HT1A antagonist, WAY 100635.
AB  - In the present study we evaluated the effects of the 5-HT(1A) receptor partial
      agonist, buspirone hydrochloride and the 5-HT(1A) receptor agonist, 8-hydroxy-2
      (di-n-propylamino) tetralin (8-OH-DPAT) on the elevated plus-maze. In addition,
      the ability of the 5-HT(1A) receptor antagonist, WAY 100635, to reverse the
      effects of both compounds was determined. 8-OH-DPAT (0.01 0.3 mg/kg, SC) dose
      dependently increased the percent time on, and the number of entries to, the open
      arms of the maze. In a second experiment, WAY 100635 (0.003 0.3 mg/kg, SC) dose
      dependently reversed the anxiolytic-like effects of 8-OH-DPAT (0.3 mg/kg, SC). In
      a third experiment, buspirone (0.3-4.0 mg/kg, SC) dose-dependently decreased the
      time spent on the open arms of the maze, indicating that it had anxiogenic-like
      effects. Buspirone also significantly decreased locomotor activity, which was
      evident in the decreases in the distance travelled on the open arms, closed arms
      and on the maze as a whole, the total number of arm entries and the mean speed of
      the animals. In contrast to its effects on 8-OH-DPAT-induced behaviours in the
      maze, WAY 100635 (0.003 1.0 mg/kg SC) failed to reverse any of the effects
      induced by buspirone. Animals treated with high doses of WAY 100635 (0.3 1.0
      mg/kg SC) alone did not significantly differ from vehicle-treated animals on any
      of the measures recorded during elevated plus-maze trials. These data suggest
      that the anxiolytic-like effects of 8-OH-DPAT, but not the anxiogenic-like
      effects of buspirone, on the elevated plus-maze are mediated via 5-HT(1A)
      receptors in the CNS.

PMID- 9272758
TI  - Analysis of sleep EEG microstructure in subchronic paroxetine treatment of
      healthy subjects.
AB  - Paroxetine is a selective and potent serotonin reuptake inhibitor and its
      efficacy for the treatment of depression has been proven. Under acute and
      subchronical treatment regimens, disturbances of the regular sleep pattern are a
      reported side effect of the drug. The present study was therefore performed to
      investigate the impact of subchronic treatment with the selective serotonin
      reuptake inhibitor paroxetine on the microstructure of the sleep EEG. The study
      especially addressed the question of subchronic effects of paroxetine medication
      (30 mg/day) in eight healthy male volunteers in a double blind, placebo
      controlled crossover design. Conventional sleep EEG parameters and a spectral
      power analysis for different sleep stages after 4 weeks of treatment were
      computed. Additionally, the correlation of certain EEG rhythms across the night
      was calculated in order to detect subtle dynamical EEG alterations, not
      necessarily obvious when regarding conventional EEG analysis. Although we could
      not detect any alterations of the spectral power values in certain frequency
      bands either during NREM nor during REM sleep following subchronic paroxetine
      medication, the dynamical EEG attributes across the night revealed a significant
      enhancement of the correlation between certain EEG rhythms mainly during NREM
      sleep.

PMID- 9272760
TI  - Reliability of an instrumental assessment of tardive dyskinesia: results from VA
      Cooperative Study #394.
AB  - Nine VA Medical Centers are participating in a 2-year double-blind placebo
      controlled study of antioxidant treatment for tardive dyskinesia (TD) conducted
      by the Department of Veteran Affairs Cooperative Studies Program. One of the
      principal outcome measures of this study is the score derived from the
      instrumental assessment of upper extremity dyskinesia. Dyskinetic hand movements
      are quantified by assessing the variability associated with steady-state
      isometric force generated by the patient. In the present report, we describe the
      training procedures and results of a multi-center reliability assessment of this
      procedure. Data from nine study centers comprising 45 individual patients with
      six trials each (three from left hand and three from right hand) were reanalyzed
      by an independent investigator and the results were subjected to reliability
      assessment. For the statistic of interest (average coefficient of variation over
      trials 2 and 3 for each hand, then take the larger of these two values), we found
      very high intraclass correlation coefficients for reliability over all patients
      across sites (ICC = 0.995). We also calculated the reliability of the measures
      across trials within patient for each combination of hand (right, left,
      dominant), rater group (site, control), and trials set (all three, trials 2 and
      3). For a given hand and trial set, the reliability of the site raters was
      similar to that of the control. This study demonstrates that instrumental
      measures for the assessment of dyskinesia are reliable and can be implemented in
      multi-center studies with minimal training.

PMID- 9272759
TI  - Opioid modulation of attention-related responses: peripheral-to-central
      progression and development of mu influence as learning occurs.
AB  - Endogenous opioids modulate attention-related bradycardiac responses evoked by
      novel stimuli and Pavlovian conditioned signals, and these effects are distinct
      from those of endogenous opioids on memory. We investigated the role of
      peripheral opioid receptors in modulating attention and Pavlovian learning, in
      rabbits tested for bradycardiac orienting responses to novel tones, and for
      Pavlovian conditioning and extinction of cardiac discrimination. Pretraining, IV
      treatment with the opiate antagonist naloxone-HCl (0.1-0.5 mg/kg) facilitated
      initial development of Pavlovian conditioned discrimination and delayed its later
      extinction, compared to saline vehicle, as previously observed. Pretraining
      treatment with its peripherally acting analog, quaternary naloxone-methiodide
      (1.29-6.47 mg/kg), also promoted initial development, but not extinction, of
      discrimination, and it reduced the magnitude of bradycardiac orienting responses
      and of tachycardiac unconditioned responses. Treatment with the selective mu
      antagonist peptide CTOP (10-30 microg/kg) facilitated conditioned responses and
      reduced unconditioned responses, somewhat later during training, but it did not
      reliably affect extinction or orienting responses. These results confirm an
      important role of peripheral opioids in regulating attentional and associative
      functions involved in orienting and the earliest stage of Pavlovian learning,
      prior to development of central opioid regulation of later associative, hedonic
      and mnemonic functions. These findings also suggest that cardiovascular opioid
      receptors might mediate peripheral opioid influences on attention and early
      association formation, via modulation of cardiac responses to stimuli and
      autonomic sensory feedback to the brain.

PMID- 9272761
TI  - The influence of chronic treatment with clonidine, yohimbine and idazoxan on
      morphine withdrawal.
AB  - Numerous previous attempts have been made to study the involvement of alpha2
      adrenoceptors in the expression of morphine withdrawal by studying the effects of
      selective alpha2-agonists and antagonists administered immediately before
      precipitation of withdrawal by an opioid antagonist such as naloxone. In the
      present investigation, we examined the effects of chronic treatment with
      clonidine (alpha2-agonist), idazoxan and yohimbine (alpha2-antagonists),
      concomitantly administered with morphine, on the expression of the withdrawal
      signs. In contrast to their acute effects, clonidine potentiated, while yohimbine
      and idazoxan attenuated the withdrawal signs precipitated by naloxone in morphine
      dependent mice. In addition, mice chronically treated only with yohimbine
      displayed withdrawal signs similar to those reported with morphine withdrawal and
      these signs were not influenced by naloxone administration. Mice chronically
      treated with clonidine displayed withdrawal signs similar to those reported with
      morphine withdrawal and these signs were further potentiated by naloxone
      administration. The results suggest that down-regulation of alpha2-adrenoceptors
      by morphine is a major adaptation contributing to development of dependence on
      opioids and also point the way to more effective treatment of narcotic
      dependence. This suggestion was based on the hypothesis that the suppression of
      noradrenergic system during chronic morphine treatment by alpha2-antagonists
      might diminish noradrenergic hyperactivity and consequently the development of
      dependence and withdrawal signs.

PMID- 9272762
TI  - Effects of clozapine, thioridazine, risperidone and haloperidol on behavioral
      tests related to extrapyramidal motor function.
AB  - Evidence indicates that the antipsychotic drug clozapine has a low propensity for
      the induction of extrapyramidal motor symptoms, and also that clozapine has
      therapeutic effects in patients with idiopathic Parkinson's disease. Because
      tacrine-induced tremulous jaw movements in rats have been suggested as a possible
      model of extrapyramidal motor dysfunctions, including parkinsonian tremor, the
      present work was undertaken to investigate the effects of clozapine on tremulous
      jaw movements. Clozapine decreased tacrine-induced tremulous jaw movements in a
      dose-related manner, with an ED50 of approximately 3.3 mg/kg. In order to
      determine the relative potency of this effect compared to other behavioral
      effects of clozapine, suppression of lever pressing was also studied. Clozapine
      reduced lever pressing in a dose-related manner, with an ED50 of approximately
      5.4 mg/kg. This indicates that clozapine suppressed jaw movements at or below the
      doses required for suppression of lever pressing. In contrast, the typical
      antipsychotic drug haloperidol failed to suppress tacrine-induced tremulous jaw
      movements in doses up to 1.0 mg/kg, which is about 11-fold higher than the ED50
      for suppression of lever pressing with that drug. Thioridazine and risperidone
      also suppressed tremulous jaw movements in roughly the same dose range at which
      lever pressing was reduced. It is possible that the suppression of tacrine
      induced tremulous jaw movements by clozapine in rats is related to the unique
      behavioral and motor effects of clozapine. The ratio of potencies of these
      effects (i.e., suppression of tremulous jaw movements versus suppression of lever
      pressing) could be used as a behavioral procedure for assessing clozapine-like
      activity in novel compounds.

PMID- 9272763
TI  - Open clinical trial on the sigma ligand panamesine in patients with
      schizophrenia.
AB  - The sigma (sigma) receptor has been proposed as a target of neuroleptic drugs.
      Preclinical data suggest that panamesine (EMD 57445), a novel sigma ligand, has
      antipsychotic effects and is free of side effects related to the extrapyramidal
      motoric system (EPMS). Here we report the results of an exploratory study aimed
      at determining the appropriate dose range and the safety of panamesine in
      patients with an acute episode of schizophrenia. The first trial with four
      patients revealed insufficient clinical efficacy of a protocol where the daily
      dosage was increased stepwise from 7.5 mg during week 1, up to 30 mg during weeks
      3 and 4. In a second set of trials, 12 patients received 15 mg at the beginning,
      this being increased up to 60 mg/day within 3 days and then maintained at this
      level for 4 weeks. As assessed by a decrease in the Brief Psychiatric Rating
      Scale score by at least 50%, five patients were judged as responders, whereas six
      patients showed only a slight improvement, and one deteriorated. Moreover, intent
      to-treat analysis showed significant improvement in psychometric variables. In
      all patients prolactin levels increased during treatment, probably due to an
      active metabolite with weak dopamine-2-receptor antagonistic effects. No major
      side effects occurred, and in particular, no EPMS symptoms were seen.

PMID- 9272764
TI  - Platelet serotonin and [3H]paroxetine binding correlate with recurrence of
      suicidal behavior.
AB  - To distinguish state- from trait-dependent associations between serotonergic
      function and suicidal behavior, platelet serotonergic measures were repeatedly
      measured, during a 1-year follow-up, in 106 patients who had recently attempted
      suicide for at least a second time. A major DSM-III-R axis I diagnosis or use of
      antidepressants were reasons for exclusion. A higher affinity constant (KD) of
      platelet [3H]paroxetine binding was related to a higher risk of short-term
      recurrence of a suicide attempt, suggesting a state relationship. Higher levels
      of platelet serotonin at baseline were a significant predictor of a recurrent
      suicide attempt within the year of follow-up, suggesting a trait relationship.
      These associations held equally within the subgroup of 73 patients with a
      borderline personality disorder. Neither the maximum number of binding sites
      (Bmax) of [3H]paroxetine nor platelet monoamine oxidase activity correlated with
      suicidality. The observed association between indicators of platelet serotonin
      uptake and suicidal behavior suggests a state- and trait-dependency between
      suicidality and central serotonergic dysfunction.

PMID- 9272765
TI  - A comparison of progressive ratio schedules versus behavioral economic measures:
      effect of an alternative reinforcer on the reinforcing efficacy of phencyclidine.
AB  - Alternative non-drug reinforcers have been demonstrated to decrease drug
      reinforced behavior by both decreasing relative reinforcing efficacy and
      substituting for the drug reinforcer. The effect of saccharin on responding
      maintained by orally delivered phencyclidine (PCP) was examined in this study
      using concurrent progressive-ratio (PR) schedules of reinforcement and a
      behavioral economic analysis of demand. Seven adult male rhesus monkeys self
      administered PCP (0.06, 0.12, 0.25, 0.50 and 1.0 mg/ml) and either concurrent
      water or saccharin (0.03% wt/vol) from two drinking spouts under concurrent
      independent PR schedules. During daily sessions the response requirements (lip
      contacts on automatic drinking spouts) increased across 15 levels, from 8 to
      4096. Each successful ratio completion resulted in the availability of 40 liquid
      deliveries under an FR 1 schedule and a subsequent increment in the PR.
      Concentrations of PCP were presented in a non-systematic order and presentation
      of the concurrent liquid, saccharin or water, was counterbalanced across
      subjects. All behaviors maintained by PCP were significantly greater than those
      maintained by water. Replacement of water with saccharin served to significantly
      decrease PCP-maintained responding and break points (BP) across the range of PCP
      concentrations; however, saccharin did not significantly decrease deliveries of
      PCP. Saccharin maintained significantly greater responding, BPs and deliveries
      compared to either PCP or water, across all PCP concentrations. The use of BP as
      a measure of reinforcing efficacy suggests that saccharin decreased the relative
      reinforcing efficacy of PCP. Furthermore, behavioral economic analyses suggested
      that saccharin decreased maximal PCP-maintained responding (Pmax) in a similar
      fashion, suggesting that BP and Pmax may be analogous measures of reinforcing
      efficacy.

PMID- 9272766
TI  - Selective inhibition of sucrose and ethanol intake by SR 141716, an antagonist of
      central cannabinoid (CB1) receptors.
AB  - SR 141716, a selective central CB1 cannabinoid receptor antagonist, markedly and
      selectively reduces sucrose feeding and drinking as well as neuropeptide Y
      induced sucrose drinking in rats. SR 141716 also decreases ethanol consumption in
      C57BL/6 mice. In contrast, blockade of CB1 receptors only marginally affects
      regular chow intake or water drinking. The active doses of SR 141716 (0.3-3
      mg/kg) are in the range known to antagonize the characteristic effects induced by
      cannabinoid receptor agonists. These results suggest for the first time that
      endogenous cannabinoid systems may modulate the appetitive value of sucrose and
      ethanol, perhaps by affecting the activity of brain reward systems.

PMID- 9272767
TI  - The effect of ambient temperature and exercise intensity on post-exercise thermal
      homeostasis.
AB  - We have previously demonstrated a prolonged (65 min or longer) elevated plateau
      of esophageal temperature (T(es)) (0.5-0.6 degrees C above pre-exercise values)
      in humans following heavy dynamic exercise (70% maximal oxygen consumption,
      VO2max) at a thermoneutral temperature (T(a)) of 29 degrees C. The elevated T(es)
      value was equal to the threshold T(es) at which active skin vasodilation was
      initiated during exercise (Th(dil)). A subsequent observation. i.e., that
      successive exercise/recovery cycles (performed at progressively increasing pre
      exercise T(es) levels) produced parallel increases of Th(dil) and the post
      exercise T(es), further supports a physiological relationship between these two
      variables. However, since all of these tests have been conducted at the same T(a)
      (29 degrees C) and exercise intensity (70% VO2max) it is possible that the
      relationship is limited to a narrow range of T(a)/exercise intensity conditions.
      Therefore, five male subjects completed 18 min of treadmill exercise followed by
      20 min of recovery in the following T(a)/exercise intensity conditions: (1) cool
      with light exercise, T(a) = 20 degrees C, 45% VO2max (CL); (2) temperature with
      heavy exercise, T(a) = 24 degrees C, 75% VO2max (TH); (3) warm with heavy
      exercise, T(a) = 29 degrees C, 75% VO2max (WH); and (4) hot with light exercise,
      T(a) = 40 degrees C, 45% VO2max (HL). An abrupt decrease in the forearm-to-finger
      temperature gradient (T(fa) - T(fi)) was used to identify the Th(dil) during
      exercise. Mean pre-exercise T(es) values were 36.80, 36.60, 36.72, and 37.20
      degrees C for CL, TH, WH, and HL conditions respectively. T(es) increased during
      exercise, and end post-exercise fell to stable values of 37.13, 37.19, 37.29, and
      37.55 degrees C for CL, TH, WH, and HL trials respectively. Each plateau value
      was significantly higher than pre-exercise values (P < 0.05). Correspondingly,
      Th(dil) values (i.e., 37.20, 37.23, 37.37, and 37.48 degrees C for CL, TH, WH,
      and HL) were comparable to the post-exercise T(es) values for each condition. The
      relationship between Th(dil) and post-exercise T(es) remained intact in all
      T(a)/exercise intensity conditions, providing further evidence that the
      relationship between these two variables is physiological and not coincidental.

PMID- 9272768
TI  - Intense exercise increases the post-exercise threshold for sweating.
AB  - We demonstrated previously that esophageal temperature (T(es)) remains elevated
      by approximately 0.5 degrees C for at least 65 min after intense exercise.
      Following exercise, average skin temperature (T(avg)) and skin blood flow
      returned rapidly to pre-exercise values even though T(es) remained elevated,
      indicating that the T(es) threshold for vasodilation is elevated during this
      period. The present study evaluates the hypothesis that the threshold for
      sweating is also increased following intense exercise. Four males and three
      females were immersed in water (water temperature, T(w) = 42 degrees C) until
      onset of sweating (Immersion 1), followed by recovery in air (air temperature,
      T(a) = 24 degrees C). At a T(a) of 24 degrees C, 15 min of cycle ergometry (70%
      VO2max) (Exercise) was then followed by 30 min of recovery. Subjects were then
      immersed again (T(w) = 42 degrees C) until onset of sweating (Immersion 2).
      Baseline T(es) and T(skavg) were 37.0 (0.1) degrees C and 32.3 (0.3) degrees C,
      respectively. Because the T(skavg) at the onset of sweating was different during
      Exercise [30.9 (0.3) degrees C] than during Immersion 1 and Immersion 2 [36.8
      (0.2) degrees C and 36.4 (0.2) degrees C, respectively] a corrected core
      temperature, T((es) (calculated)), was calculated at a single designated skin
      temperature, T((sk)(designated)), as follows: T((es)(calculated)) = T(es) +
      [beta/(1-beta)][T(skavg)-T((sk)(designated))]. The T((sk)(designated)) was set at
      36.5 degrees C (mean of Immersion 1 and Immersion 2 conditions) and beta
      represents the fractional contribution of T(skavg) to the sweating response (beta
      for sweating = 0.1). While T((es)(calculated)) at the onset of sweating was
      significantly lower during exercise [36.7 (0.2) degrees C] than during Immersion
      1 [37.1 (0.1) degrees C], the threshold of sweating during Immersion 2 [37.3
      (0.1) degrees C] was greater than during both Exercise and Immersion 1 (P <
      0.05). We conclude that intense exercise decreases the sweating threshold during
      exercise itself, but elicits a subsequent short-term increase in the resting
      sweating threshold.

PMID- 9272769
TI  - Relationship between maximal oxygen uptake on different ergometers, lean arm
      volume and strength in paraplegic subjects.
AB  - The present experiment was designed to study the importance of strength and
      muscle mass as factors limiting maximal oxygen uptake (VO2max) in wheelchair
      subjects. Thirteen paraplegic subjects [mean age 29.8 (8.7) years] were studied
      during continuous incremental exercises until exhaustion on an arm-cranking
      ergometer (AC), a wheelchair ergometer (WE) and motor-driven treadmill (TM). Lean
      arm volume (LAV) was estimated using an anthropometric method based upon the
      measurement of various circumferences of the arm and forearm. Maximal strength
      (MVF) was measured while pushing on the rim of the wheelchair for three positions
      of the hand on the rim (-30 degrees, 0 degrees and +30 degrees). The results
      indicate that paraplegic subjects reached a similar VO2max [1.23 (0.34) 1 x min(
      1), 1.25 (0.38) 1 x min(-1), 1.22 (0.18) 1 x min(-1) for AC, TM and WE,
      respectively] and VO2max/body mass [19.7 (5.2) ml x min(-1) x kg(-1), 19.5 (6.14)
      ml x min(-1) x kg(-1), 19.18 (4.27) ml x min(-1) x kg(-1) for AC, TM and WE,
      respectively on the three ergometers. Maximal heart rate f((c) (max)) during the
      last minute of AC (173 (17) beats x min(-1)], TM [168 (14) beats x min(-1)], and
      WE [165 (16) beats x min(-1)], were correlated, but f((c) (max)) was
      significantly higher for AC than for TM (P < 0.03). There were significant
      correlations between MVF and LAV (P < 0.001) and between the MVF data obtained at
      different angles of the hand on the rim [311.9 (90.1) N, 313.2 (81.2) N, 257.1
      (71) N, at -30 degrees, 0 degrees and +30 degrees, respectively]. There was no
      correlation between VO2max and LAV or MVF. The relatively low values of f((c)
      (max)) suggest that VO2max was, at least in part, limited by local aerobic
      factors instead of central cardiovascular factors. On the other hand, the lack of
      a significant correlation between VO2max and MVF or muscle mass was not in favour
      of muscle strength being the main factor limiting VO2max in our subjects.

PMID- 9272770
TI  - The effect of a low-carbohydrate diet on performance, hormonal and metabolic
      responses to a 30-s bout of supramaximal exercise.
AB  - The aim of this study was to find out whether a low-carbohydrate diet (L-CHO)
      affects: (1) the capacity for all-out anaerobic exercise, and (2) hormonal and
      metabolic responses to this type of exercise. To this purpose, eight healthy
      subjects underwent a 30-s bicycle Wingate test preceded by either 3 days of a
      controlled mixed diet (130 kJ/kg of body mass daily, 50% carbohydrate, 30% fat,
      20% protein) or 3 days of an isoenergetic L-CHO diet (up to 5% carbohydrate, 50%
      fat, 45% protein) in a randomized order. Before and during 1 h after the exercise
      venous blood samples were taken for measurement of blood lactate (LA), beta
      hydroxybutyrate (beta-HB), glucose, adrenaline (A), noradrenaline (NA) and
      insulin levels. Oxygen consumption (VO2) was also determined. It was found that
      the L-CHO diet diminished the mean power output during the 30-s exercise bout
      [533 (7) W vs 581 (7) W, P < 0.05] without changing the maximal power attained
      during the first or second 5-s interval of the exercise. In comparison with the
      data obtained after the consumption of a mixed diet, after the consumption of a L
      CHO diet resting plasma concentrations of beta-HB [2.38 (0.18) vs 0.23 (0.01)
      mmol x l(-1), P < 0.001] and NA [4.81 (0.68) vs 2.2 (0.31) nmol x l(-1), P <
      0.05] were higher, while glucose [4.6 (0.1) vs 5.7 (0.2) mmol x l(-1), P < 0.05]
      and insulin concentrations [11.9 (0.9) vs 21.8 (1.8) mU x l(-1)] were lower. The
      1-h post-exercise excess of VO2 [9.1 (0.25) vs 10.6 (0.25) 1, P < 0.05], and
      blood LA measured 3 min after the exercise [9.5 (0.4) vs 10.6 (0.5) mmol x l(-1),
      P < 0.05] were lower following the L-CHO treatment, whilst plasma NA and A
      concentrations reached higher values [2.24 (0.40) vs 1.21 (0.13) nmol x l(-1) and
      14.30 (1.41) vs 8.20 (1.31) nmol x l(-1), P < 0.01, respectively]. In subjects on
      the L-CHO diet, the plasma beta-HB concentration decreased quickly after
      exercise, attaining approximately 30% of the pre-exercise value within 60 min,
      while insulin and glucose levels were elevated. The main conclusions of this
      study are: (1) a L-CHO diet is detrimental to anaerobic work capacity, possibly
      because of a reduced muscle glycogen store and decreased rate of glycolysis; (2)
      reduced carbohydrate intake for 3 days enhances activity of the sympathoadrenal
      system at rest and after exercise.

PMID- 9272771
TI  - Moderate endurance training has no effect on the parathyroid function of heart
      transplant patients.
AB  - The benefit of retraining for heart transplant recipients (HTR) is now well
      established. The rehabilitation of these patients can be compromised by
      osteopenia and bone fractures. The resting levels of parathyroid hormone (PTH)
      and exercise-induced increases are higher in HTR than in healthy controls. To
      evaluate the effect of a moderate endurance training programme on parathyroid
      activity, six HTR, an average of 18 months after transplant, and seven healthy
      sedentary controls have been studied. None of the subjects had a history of bone
      disease. Two exercise tests (square wave endurance exercise tests, SWEET) with
      identical work rates were performed before and after training. Intact PTH,
      ionized calcium (Ca2+), phosphorus (Pi) and pH were measured at rest, during
      exercise and in the recovery periods. Training consisted of a 45-min SWEET three
      times a week for 6 weeks. Levels of Ca2+, Pi and PTH showed a significant
      increase during the exercise session in both groups. Ca2+ and Pi levels decreased
      rapidly after the cessation of exercise whereas PTH reached a peak at the 10th
      min of the recovery in both groups. This increase in PTH was significantly higher
      in HTR than in controls. However, despite a significant improvement of total
      endurance work (+ 28% in HTR, +29% in controls) this endurance training had no
      effect on resting levels of PTH, plasma Ca2+ or Pi, nor on their exercise-induced
      variations. The exercise-induced decrease in pH was less pronounced after
      training which is evidence of training. We conclude that a short endurance
      training programme does not alter the moderate hyperparathyroidism of HTR. The
      effect of such a training programme on bone mass and bone mineral density needs
      now to be evaluated.

PMID- 9272772
TI  - The effects of maturation on self-induced dynamic body sway frequencies of girls
      performing acrobatics or classical dance.
AB  - We investigated the effects of maturation on the dynamic body sways of healthy
      girls. Prepubertal and postpubertal girls practising professional physical
      activities requiring a good ability to maintain equilibrium (acrobats and
      dancers) were asked to stand on a free seesaw platform and the results compared
      to those for untrained age-matched girls. This platform (stabilometer) allows
      self-induced body sways. Stabilograms were obtained by a double integration of
      the angular acceleration from the recordings of the platform sways made with an
      accelerometer. Fast Fourier transform processing of stabilograms allowed spectral
      frequency analysis. The total spectrum energy and the energies of three frequency
      bands (0-0.5 Hz, 0.5-2 Hz, 2-20 Hz) were determined. ANOVA showed that, for all
      groups of different equilibrium activity and independent of visual input,
      prepubertal girls had higher energy values than postpubertal girls in the 0- to
      0.5-Hz band whereas the opposite was true for 0.5- to 2-Hz band. Ballet dancers
      were more dependent than acrobats on visual inputs for the regulation of their
      postural control but were less dependent than untrained girls at both ages.
      Maturation seemed to shift body sways towards higher frequencies and the
      utilization of the cues of postural control was different according to the type
      of equilibrium activity practised by the subjects.

PMID- 9272774
TI  - Prediction of normal values for lactate threshold estimated by gas exchange in
      men and women.
AB  - Lactate threshold (LT) is an index of exercise capacity and can be estimated from
      the gas exchange consequences of a metabolic acidosis (LT(GE)). In recent years,
      it has emerged as a diagnostic tool in the evaluation of subjects with exercise
      limitation. The purpose of this study was to develop LT(GE) prediction equations
      on a relatively large sample of adults and to cross-validate each equation. A
      total of 204 healthy, sedentary, nonsmoking subjects (103 men and 101 women),
      aged 20-70 years, underwent graded exercise testing on a cycle ergometer. The V
      slope technique was used to detect LTGE as the oxygen uptake (VO2) at the
      breakpoint of the carbon dioxide output versus VO2 relationship. Multiple linear
      regression was used to develop 12 equations with combinations of the following
      predictor variables: age, height, body mass, and fat-free mass. Eight of the
      equations are gender-specific and four are generalized with gender as a dummy
      variable. The equations were cross-validated using the predicted residual sum of
      squares (PRESS) method. The results demonstrate that the equations had relatively
      high multiple correlations (0.577-0.863) and low standard errors of the estimate
      (0.123-0.228 1 x min(-1)). The PRESS method demonstrated that the equations are
      generalizable, i.e., can be used in future studies without a significant loss of
      accuracy. Since we tested only healthy, sedentary subjects, our equations can be
      used to predict the lower limit of normal for a given subject. Using individual
      data for healthy and diseased subjects from the literature, we found that our
      gender-specific equations rarely miscategorized subjects unless they were obese
      and mass was a predictor variable. We conclude that our equations provide
      accurate predictions of normal values for LT(GE) and that they are generalizable
      to other subject populations.

PMID- 9272773
TI  - Spectral analysis of heart rate variability during heat exposure and repeated
      exercise.
AB  - This study examined indices of parasympathetic (PNS) and sympathetic (SNS) nerve
      activity during exposure to heat and/or two successive bouts of exercise. Seven
      healthy males [age = 27.1 (3.6) years; mean (SD), maximum oxygen consumption
      (VO2max) = 48.1 (7.6) ml x kg(-1) x min(-1)] were assigned to each of four
      experimental conditions according to a randomized-block design. While in a
      thermoneutral (23 degrees C) or heated (40 degrees C, 30% relative humidity)
      climatic chamber subjects performed exercise on a cycle ergometer (two 30-min
      bouts at approximately 50% VO2max, separated by a 45-min recovery period, (CEx
      and HEx, respectively) or remained seated (CS and HS, respectively) for 2 h. The
      R-R intervals of the subjects' ECGs were analyzed for selected near-steady-state
      time periods [termed Phase I (25-40 min) and Phase II (100-115 min)] according to
      the method of Yamamoto and Hughson (J Appl Physiol 71:1143-1150, 1991). Total
      (P(T)), low-frequency (P(LF) = 0-0.15 Hz) and high-frequency (P(HF) = 0.15-0.5
      Hz) power spectra were calculated using coarse-graining spectral analysis. Heat
      exposure alone did not alter autonomic balance or levels of circulating
      catecholamines significantly. Exercise in both environmental conditions induced a
      significant decrease in an index of PNS tone (PHF:PT) [PNS indicator for CS =
      0.084 (0.04) vs CEx = 0.023 (0.015) and HS = 0.065 (0.027) vs HEx = 0.015
      (0.009)], with an increase in catecholamine concentrations. Although the index of
      SNS activity (P(LF):P(HF)) tended to rise with exercise in both environmental
      conditions, increments reached levels of significance only during exercise in the
      heat [SNS indicator for CS = 8.22 (5.58) vs CEx = 34.06 (21.73) and HS = 8.94
      (5.49) vs HEx = 54.29 (49.80)]. The relative magnitudes of SNS and PNS indicators
      did not differ significantly between the first and second bouts of exercise.
      These results indicate the substantial contribution of vagal withdrawal and
      catecholamine secretion to the increase in heart rate that occurs during repeated
      moderate exercise at room temperature and the additional contribution from SNS
      activity during such exercise in the heat.

PMID- 9272775
TI  - Moderate and exhaustive endurance exercise influences the interferon-gamma levels
      in whole-blood culture supernatants.
AB  - The aim of this study was to investigate whether moderate or exhaustive endurance
      exercise influences cytokine levels in whole-blood culture supernatants after
      stimulation. Therefore, eight healthy subjects were first exposed to moderate
      exercise on a cycle ergometer for 30 min at 70% of their 4-mmol/l lactic acid
      (anaerobic) threshold, and 1 week later to exhaustion (for 90 min) at their
      anaerobic threshold. Blood samples were taken before, 30 min after and 24 h after
      each exercise bout. The following lymphocyte subpopulations were determined: CD14
      positive(+)/CD45+, CD4+, CD8+, and CD16+. Cytokine levels in the supernatants
      were measured by enzyme-linked immunosorbent assay (ELISA). Production of
      interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)-alpha were induced
      with lipopolysaccharides (LPS), and that of IL-2 and interferon (IFN)-gamma with
      staphylococcal enterotoxin B (SEB) and phytohaemagglutinin (PHA). Cortisol levels
      were also determined by ELISA. The lymphocyte subset distribution was observed to
      be unchanged after moderate exercise. Thirty minutes after exhaustive exercise,
      the CD16+ count was found to be significantly lower, whereas 24 h later the CD4+
      count was significantly higher than pre-exercise counts. Moderate exercise
      influenced the IFN-gamma production (PHA-stimulated), which increased
      significantly from 974 (391) pg/ml before exercise to 1450 (498) pg/ml 24 h
      later. Thirty minutes after exhaustive exercise the IFN-gamma level in the
      supernatants (SEB-stimulated) was significantly decreased (from 14470 (11840)
      pg/ml before exercise to 6000 (4950) pg/ml after exercise). The IL-1beta and TNF
      alpha production per monocyte was also significantly reduced.

PMID- 9272776
TI  - Decreased pulmonary diffusing capacity of divers over a 6-year period.
AB  - Non-smoking, male, professional firemen divers (n = 15) underwent two pulmonary
      function tests (PFT) separated by 6 years. Measured data were compared to
      European Coal Steel Community recommended reference values to permit cross
      sectional and then longitudinal study. Higher vital capacity (VC; P < 0.01) and
      forced expiratory volume in 1 s (FEV1; P < 0.05), and lower maximal mid
      expiratory flow (MMEF) coefficient with VC (MMEF/VC; P < 0.05) were observed in
      both PFT. Diver's pulmonary diffusing capacity (DL(CO)) and the coefficient with
      alveolar volume (DL(CO)/V(A)) showed significantly (P < 0.001) different
      evolution profiles than those expected from predicted values. In divers, DL(CO)
      and DL(CO)/V(A) decreased from 104.0% to 91.4% and from 106.4% to 91.5% of
      predicted values respectively. Changes in DL(CO) and DL(CO)/V(A) correlated
      positively with the initial measurement of DL(CO) (r = 0.67, P < 0.01) and
      DL(CO)/V(A) (r = 0.74, P < 0.01) respectively, whereas no correlation between
      changes in pulmonary gas transfer function and age or diving history parameters
      was found. Thus, it is suggested from our observations that hyperbaric atmosphere
      exposure increases the effects of aging on pulmonary diffusing capacity and that
      pulmonary gas transfer function should be regularly tested in professional and
      recreational divers.

PMID- 9272777
TI  - Arterial blood pressure and forearm vascular conductance responses to sustained
      and rhythmic isometric exercise and arterial occlusion in trained rock climbers
      and untrained sedentary subjects.
AB  - Cardiovascular responses to sustained and rhythmic (5 s on, 2 s off) forearm
      isometric exercise to fatigue at 40% maximal voluntary contraction (MVC) and to a
      period of arterial occlusion were investigated in elite rock climbers (CLIMB) as
      a trained population compared to non-climbing sedentary subjects (SED). Blood
      pressure (BP), monitored continuously by Finapres, and forearm blood flow, by
      venous occlusion plethysmography, were measured and used to calculate vascular
      conductance. During sustained exercise, times to fatigue were not different
      between CLIMB and SED. However, peak increases in systolic (S) BP were
      significantly lower in CLIMB [25 (13) mmHg; (3.3 (1.7) kPa] than in SED [48 (17)
      mmHg; (6.4 (2.3) kPa] (P < 0.05), with a similar trend for increases in diastolic
      (D) BP. Immediately after sustained exercise, forearm conductance was higher in
      CLIMB than SED (P < 0.05) for up to 2 min. During rhythmic exercise, times to
      fatigue were two fold longer in CLIMB than SED [853 (76) vs 420 (69) s, P <
      0.05]. Increases in SBP were not different between groups except during the last
      quarter of exercise when they fell in CLIMB. Conductance both during and after
      rhythmic exercise was higher in CLIMB than in SED. Following a 10-min arterial
      occlusion, peak vascular conductance was significantly greater in CLIMB than SED
      [0.597 (0.084) vs 0.431 (0.035) ml x min(-1) x 100 ml(-1) x mmHg(-1); P < 0.05].
      The attenuated BP response to sustained isometric exercise could be due in part
      to enhanced forearm vasodilatory capacity, which also supports greater endurance
      during rhythmic exercise by permitting greater functional hyperaemia in between
      contraction phases. Such adaptations would all facilitate the ability of rock
      climbers to perform their task of making repetitive sustained contractions.

PMID- 9272778
TI  - Sweat distribution before and after repeated heat exposure.
AB  - We investigated the impact of short-term, moderate humidity heat acclimation upon
      sweat distribution. Eight males completed six daily heat exposures [cycling:
      ambient temperature 39.5 (0.2) degrees C, relative humidity 59.2 (0.8)%], during
      which auditory canal temperature (T(ac)) was maintained 1.4 degrees C above pre
      exposure levels for 70 min by manipulating the work rate. On days 1 and 6, T(ac)
      and local sweat rates (m(sw): eight sites) were monitored. The pre-exposure,
      resting T(ac) and the T(ac) sweat threshold decreased from day 1 to day 6 [36.83
      (0.05) degrees C vs 36.62 (0.05) degrees C, and 36.90 (0.05) degrees C vs 36.75
      (0.05) degrees C, respectively; both P < 0.05]. However, the sweat-onset time,
      sweat sensitivity (delta m(sw)/deltaT(ac)) and established m(sw) were unaltered
      (P > 0.05). There was also no evidence of a post-acclimation redistribution in
      established m(sw) between the eight skin regions, though both the sweat
      sensitivity and established m(sw) for the forehead and hand were significantly
      greater than at the remaining sites (P < 0.05). It is concluded that the 5-day
      heat acclimation regimen provided only a minimal stimulus for sudomotor
      adaptation.

PMID- 9272779
TI  - Monitoring high-intensity endurance training using neuromuscular excitability to
      recognize overtraining.
AB  - The minimal rectangular current pulse that produces a single contraction of
      reference muscles at different pulse durations has been recommended as a marker
      of the neuromuscular excitability (NME) of skeletal muscles. NME is improved in
      well-trained, non-fatigued endurance athletes and deteriorates after prolonged
      heavy exercise and high-volume overtraining. The hypothesis was tested that a
      deterioration in NME also indicates an early stage in the overtraining process
      during high-intensity endurance training. Six subjects participated for 40-60 min
      per day in a 6-week, 6-days-per-week, intensive, steady-state and interval
      training program using a cycle ergometer. Training was stopped each day on
      volitional exhaustion. On day 7 of each week training was of low intensity for
      about 30-40 min. Submaximum and maximum power output were significantly increased
      after 3 weeks, but there was no further improvement, rather a deterioration after
      week 6 compared to week 3. Even after 2 weeks of regeneration no
      supercompensation was evident, rather a decrease in maximum power output. NME was
      slightly improved after 3 weeks, but deteriorated after 6 weeks, and was again
      normalized after 2 weeks of regeneration. The discrepancy between normalization
      of NME and still-deteriorated performance ability after 2 weeks of regeneration
      reflects additional significant, and probably central mechanisms that explain
      persistent performance incompetence. Deterioration in NME may indicate an early
      stage in the overtraining process during high-volume as well as high-intensity
      endurance overtraining, but normalization does not necessarily indicate
      sufficient regeneration.

PMID- 9272780
TI  - Moderate exercise leads to decreased expression of beta1 and beta2 integrins on
      leucocytes.
AB  - Intravascular adhesion of leucocytes plays a role in the pathogenesis of acute
      and chronic vascular disease. Regular aerobic exercise seems to protect against
      vascular disease. Since leucocyte adhesion is mediated by integrins, we tested
      the hypothesis that surface expression of the integrin adhesive receptors LFA-1
      (cd11a/cd18), MAC-1 (cd11b/cd18), gp 150/95 (cd11c/cd18), and VLA-4 (cd29/cd49)
      is decreased by moderate endurance exercise. Surface expression of integrins was
      measured by FACS analysis in 19 healthy subjects (16 males, 3 females, 36.6 +/-
      8.7 years, 177.1 +/- 7.5 cm, 70.3 +/- 8.1 kg) before and after submaximal
      exercise (3 h run) using monoclonal antibodies against cd11a, cd11b, cd11c, cd18,
      cd29 and cd49. In addition, we compared resting integrin expression in this group
      with a group of sedentary subjects (19 males, 6 females, 29.3 +/- 5.3 years).
      White blood cell count increased from 5300 ml(-1) to 9740 ml(-1) during exercise
      (P < 0.001). Nevertheless, the expression (indicated by the mean log
      fluorescence) of cd11a (94 +/- 24 vs. 78 +/- 14) and cd18 (128 +/- 31 vs. 102 +/-
      21) on lymphocytes and of cd11a (104 +/- 25 vs. 85 +/- 16), cd11c (497 +/- 171
      vs. 408 +/- 126) cd29 (109 +/- 16 vs. 89 +/- 16), cd49 (69 +/- 8 vs. 54 +/- 11)
      on monocytes was decreased after exercise (all P < 0.05). In contrast, integrin
      expression on granulocytes was not altered by exercise. Comparison of exercising
      and sedentary subjects showed a significantly decreased expression of integrins
      in exercising subjects. Our results demonstrate that moderate exercise leads to
      decreased expression of integrin receptors on leucocytes. This decreased
      expression of adhesion molecules may result in decreased adhesion and
      infiltration of leucocytes into the vessel wall. This phenomenon may play a role
      in the beneficial effect of moderate exercise in prevention of acute and chronic
      vascular disease.

PMID- 9272781
TI  - Pharmacological tests in pain analysis and in prediction of treatment outcome.

PMID- 9272782
TI  - Pharmacological classification of central post-stroke pain: comparison with the
      results of chronic motor cortex stimulation therapy.
AB  - In an attempt to clarify the neurochemical background of central post-stroke pain
      and to undertake a pharmacological analysis, the basic pharmacological
      characteristics of this intractable pain syndrome were investigated by the
      morphine, thiamylal and ketamine tests. In addition, the correlation between the
      pharmacological characteristics and the effects of chronic motor cortex
      stimulation therapy was examined. The study employed 39 central post-stroke pain
      patients who had intractable hemibody pain associated with dysesthesias, and
      radiologically demonstrated lesions in the thalamic area (thalamic pain, n = 25)
      or suprathalamic area (suprathalamic pain, n = 14). The pharmacological
      evaluations showed that definite pain reduction occurred in eight of the 39 cases
      (20.5%) by the morphine test, in 22 of the 39 cases (56.4%) by the thiamylal
      test, and in 11 of 23 cases (47.8%) by the ketamine test. Based on these
      pharmacological assessments, there was no obvious difference between thalamic and
      suprathalamic pain. A comparison of the long-term follow-up results of chronic
      motor cortex stimulation therapy revealed that thiamylal and ketamine-sensitive
      and morphine-resistant cases displayed long-lasting pain reduction with chronic
      motor cortex stimulation therapy, whereas the remaining cases did not show good
      results. We conclude that pharmacological classification of central post-stroke
      pain by the morphine, thiamylal and ketamine tests could be useful for predicting
      the effects of chronic motor cortex stimulation therapy. It has recently been
      suggested that excitatory amino acids may be involved in the development of
      central post-stroke pain. However, the fact that only 23 of the present 39 cases
      (59.0%) of thalamic and suprathalamic pain were sensitive to the thiamylal or
      ketamine test reflects the complex pharmacological background and the
      difficulties associated with treating central post-stroke pain.

PMID- 9272783
TI  - A longitudinal study of somesthetic perceptual disorders in an individual with a
      unilateral thalamic lesion.
AB  - Several aspects of tactile, thermal and pain perception were evaluated in an
      individual (R.S.) with a hemorrhagic lesion centered in her left lateral
      thalamus. Over a 4-year period, psychophysical evaluations were undertaken every
      6-8 months, and five magnetic resonance (MR) studies were conducted. Early tests
      (1991-1992) revealed large contralateral deficits in R.S.'s perception of touch,
      innocuous temperature, and mechanically evoked cutaneous pain--more so for the
      upper versus the lower extremity. R.S. showed a similar pattern for heat pain
      sensitivity, but a more modest deficit than for mechanically evoked pain. She
      showed a deficit for cold pain sensitivity on her foot, but not for her hand.
      Thresholds for all types of stimuli ipsilateral to the lesion were within a
      normative range. Late in 1993, R.S. demonstrated improvements in sensory capacity
      for touch and mechanically evoked pain contralaterally, although deficits were
      still evident. During the same period, heat pain sensitivity improved
      contralaterally, and strikingly, a permanent, ipsilateral hypersensitivity to
      heat pain developed in her hand. Throughout the entire testing period, R.S.'s
      ratings of perceived unpleasantness matched the patterns of perceived pain
      intensity. Thus, the discriminative and the affective dimensions of her pain
      would change in tandem. However, perceptible innocuous thermal stimuli evoked no
      affective response when applied contralaterally, despite being described as
      pleasant when presented ipsilaterally. Throughout the testing period, R.S.
      reported a persistent numbness on her right hemi-body. Only during a 3-month
      period in 1995 did she experience spontaneous pain, which was referred to her
      right foot. The only change in psychophysical performance related to her right
      foot was a transient but intense thermal allodynia several months prior to her
      spontaneous pain. The MR studies over this 4-year period showed changes in the
      extent of edema, gliosis and/or ischemia that could be related to perceptual
      changes. Thus, the conspicuous observations in this thalamic lesion case were:
      (i) differential effects upon the various pain modalities (mechanical, heat and
      cold); (ii) development of thermal allodynia without mechanical allodynia,
      including an ipsilateral effect; (iii) a deficit in positive affective responses
      to temperature; and (iv) the different time courses for changes in evoked
      somesthetic capacity versus spontaneous paresthesias and pathological pain.

PMID- 9272784
TI  - Do patients with chronic pain selectively attend to pain-related information?:
      preliminary evidence for the mediating role of fear.
AB  - Preliminary evidence from a study using a modified Stroop paradigm suggests that
      individuals with chronic pain selectively attend to pain-related information. The
      current study was conducted in an attempt to replicate and extend this finding.
      Nineteen patients with chronic pain stemming from musculoskeletal injury and 22
      healthy control subjects participated. All participants completed a computerised
      task designed to evaluate attentional allocation to cues thematically related to
      pain and injury via measurement of detection latencies for dot-probes that
      followed their presentation. Results indicated that patients did not differ from
      control subjects in their pattern of responses to dot-probes that were presented
      following either the pain- or injury-related cues. This pattern of results
      continued to hold true after including level of depression as a covariate in the
      analysis. However, when patients were divided on the basis of scores on the
      Anxiety Sensitivity Index (Peterson, R.A. and Reiss, S., Anxiety Sensitivity
      Index Manual, 2nd edn., International Diagnostic Systems, Worthington, OH, 1992),
      a measure related to fear of pain (Asmundson, G.J.G. and Norton, G.R., Behav.
      Res. Ther., 34 (1996) 545-554), those with low anxiety sensitivity shifted
      attention away from stimuli related to pain whereas those with high anxiety
      sensitivity responded similarly to dot-probes regardless of the parameters of
      presentation. These results suggest that the operation of the information
      processing system in patients with chronic pain may be dependent on a patient's
      trait predisposition to fear pain. Theoretical and ecological implications are
      discussed.

PMID- 9272785
TI  - Children's Pain Perspectives Inventory (CPPI): developmental assessment.
AB  - This study explored the reliability and validity of the Children's Pain
      Perspectives Inventory (CPPI), an instrument designed to assess the developmental
      progression of children's pain perspectives. The convenience sample included 88
      children between 5 and 13 years of age. Results from this descriptive
      correlational study indicated that children's pain perspectives could be
      developmentally ordered, coded and scored reliably, and with validity. An
      interrater reliability of 0.94 and an internal consistency reliability of 0.86
      was obtained on the final group of 48 children. The criterion validity of the
      CPPI was supported by significant positive correlations between scores on the
      CPPI and the Cartoon Conservation Scale (CCS), a measure of cognitive development
      (r = 0.67, P = 0.001). Additional testing and refinement of the CPPI is
      recommended.

PMID- 9272786
TI  - Tetrodotoxin inhibits neuropathic ectopic activity in neuromas, dorsal root
      ganglia and dorsal horn neurons.
AB  - Neuropathic pain or persistent dysesthesias may be initiated by mechanical,
      chemical, or ischemic damage to peripheral sensory nerves. In animal models of
      neuropathic pain, transection or constrictive injury to peripheral nerves
      produces ectopic discharges originating at both injury sites and related dorsal
      root ganglia (DRG), and, consequently, hyperexcitability in associated dorsal
      horn (DH) neurons of the spinal cord. Since ectopic discharges are inhibited by
      agents that block voltage-sensitive Na+ channels, it has been postulated that
      accumulation of Na+ channels in the membrane at nerve injury sites may contribute
      to, or be responsible for, the development of ectopic neuronal activity (ENA).
      The present study therefore, tested the sensitivity of ENA to intravenously
      administered tetrodotoxin (TTX), an extremely potent and selective Na+ channel
      blocker. Comparative effects of TTX on cardiac parameters such as heart rate (HR)
      and diastolic blood pressure (DBP) were also studied. Experiments were performed
      on adult male Sprague-Dawley rats in which the common sciatic nerve had been
      transected 4-10 days earlier. Neuromal activity was measured in fine bundles of
      microfilaments teased from sciatic nerves, and extracellular microelectrode
      recordings were made from DRG and DH neurons. Cardiovascular parameters were
      recorded simultaneously. Intravenously administered TTX induced dose-dependent
      inhibition of ENA, with that originating from neuromas being the most sensitive;
      ED50 values (expressed as microg/kg, with 95% confidence limits) for neuromal,
      DRG and DH neuron activity were: 0.8 (0.6-1.2), 4.3 (2.2-8.4) and 36.2 (16.1
      81.3), respectively. Inhibition of ENA in neuromas and DRG did not recover within
      10 min after 100 or 300 microg/kg TTX. By comparison, the ED50 value for the
      initial decrease of HR was 17.9 (15.0-21.5) microg/kg, and partial recovery
      occurred within approximately 3 min. These data support the hypothesis that Na+
      channel accumulation contributes to the generation of ectopic discharges in
      neuromas and DRG, and suggest that TTX-sensitive Na+ channels located at the
      nerve injury site and DRG play an important role in the genesis of neuropathic
      pain.

PMID- 9272787
TI  - An in vitro study of ectopic discharge generation and adrenergic sensitivity in
      the intact, nerve-injured rat dorsal root ganglion.
AB  - A chronic, loose constriction of the sciatic nerve in rat produces behavioral
      signs of spontaneous pain and cutaneous hyperalgesia (Bennett and Xie, Pain, 33
      (1988) 87-107) as well as an abnormal spontaneous activity and adrenergic
      sensitivity of certain dorsal root ganglion (DRG) cells with axons in the injured
      nerve (Kajander et al., Neurosci. Lett., 138 (1992) 225-228; Xie et al., J.
      Neurophysiol., 73 (1995)1811-1820). The present study investigated whether the
      spontaneous activity and adrenergic sensitivity were intrinsic properties of
      injured DRG cells and manifested in vitro, i.e., not dependent on intact blood
      circulation and an intact, functioning sympathetic nervous system. Two weeks
      after a loose constriction of the sciatic nerve, the L4 or L5 DRG with its
      ligated nerve and dorsal root attached was removed from the rat and placed in a
      chamber. Extracellular recordings were made from teased dorsal root fibers.
      Spontaneous activity (>0.05 imp/s in 3 min) originating within or close to the
      DRG was often found in C-, Adelta- and Abeta-fibers from nerve-injured rats, but
      was rare in fibers with peripheral axons from uninjured nerve. The incidence of
      various patterns of spontaneous discharge was similar to that previously recorded
      in vivo. Nineteen of 30 C-fibers, four of five Adelta- and three of seven Abeta
      fibers from injured nerve responded to different doses of norepinephrine (NE)
      applied topically to the DRG. Five of seven C- and one of two Abeta -fibers from
      injured nerve responded to clonidine, a more selective alpha2 adrenergic agonist.
      The thresholds ranged from 500 to 10 microM, the lowest dose delivered. None of
      the fibers from uninjured nerve responded to NE or clonidine (500 microM). Since
      the experiments were carried out in vitro in the intact DRG, the existence of
      spontaneous activity in DRG cells in nerve-injured rats was independent of any
      blood borne chemicals, such as norepinephrine. We hypothesize that abnormal
      activity and adrenergic sensitivity in injured DRG neurons are due to an
      intrinsic alteration of the cell body membrane.

PMID- 9272788
TI  - Lumbar transplants of immortalized serotonergic neurons alleviate chronic
      neuropathic pain.
AB  - The RN46A cell line was derived from embryonic day 13 rat medullary raphe cells
      by infection with a retrovirus encoding the temperature-sensitive mutant of SV40
      large T antigen. This cell line is neuronally restricted and constitutively
      differentiates following a shift to non-permissive temperature. Brain-derived
      neurotrophic factor (BDNF) induced the serotonergic phenotype and increased the
      survival of RN46A cells in vitro. After transfection of the rat BDNF gene into
      RN46A cells, an autocrine BDNF-secreting cell line, 46A-B14, was isolated and
      transplanted into the rat CNS. Transplanted 46A-B14 cells had increased survival
      and enhanced serotonin (5HT) synthesis compared to 46A-V1 cells, RN46A cells
      transfected with vector-alone. When 46A-B14 cells were transplanted in the lumbar
      subarachnoid space of the spinal cord 1 week after a chronic constriction injury
      (CCI) of the sciatic nerve, they survived longer than 6 weeks on the pia mater.
      Furthermore, the tactile and cold allodynia and thermal hyperalgesia induced by
      CCI was significantly reduced during a 4-6- week period. The maximal effect
      occurred 1 week after transplantation. 46A-V1 cells, transplanted after CCI, did
      not survive beyond 2-3 weeks and had no effect on the allodynia and hyperalgesia
      induced by CCI. Acute intrathecal injection of the 5HT receptor antagonist
      methysergide decreased the antinociceptive effects of the 46A-B14 cells to pre
      transplant levels. These data suggest that a chronically applied, low local dose
      of serotonin near the dorsal horn was able to reverse the development of chronic
      neuropathic pain following CCI. The use of neural cell lines that are able to
      deliver inhibitory neurotransmitters such as serotonin, in a model of chronic
      pain offers a novel approach to pain management.

PMID- 9272789
TI  - Wallerian degeneration is required for both neuropathic pain and sympathetic
      sprouting into the DRG.
AB  - Chronic loose constriction of the sciatic nerve produces mechanoallodynia and
      thermal hyperalgesia in rats and mice, and the behaviour develops during the time
      in which the nerve distal to the ligature site is undergoing Wallerian
      degeneration. There is a sympathetic component to the pain generated by this and
      other rodent models of neuropathic pain, yet the site at which this sympathetic
      sensory coupling remains unknown. It has been shown that following sciatic nerve
      transection or spinal nerve lesion, sympathetic axons invade the dorsal root
      ganglion (DRG) where they sometimes form pericellular baskets around mostly large
      diameter DRG neurons--a possible anatomical substrate for sympathetically
      maintained pain (SMP). The signal for the sympathetic invasion of the DRG has not
      yet been shown, but associated with Wallerian degeneration is the upregulation of
      nerve growth factor (NGF) in the distal stump of the partially injured nerve,
      which may be retrograde-transported to the DRG in uninjured sensory axons to
      induce sprouting of sympathetic axons. To investigate the role of Wallerian
      degeneration in the development of neuropathic pain and sympathetic sprouting in
      the DRG, we have made use of a strain of mouse (C57B1/Wld) in which Wallerian
      degeneration following nerve injury is delayed. We gave wild-type or Wld mice
      chronic constriction injuries (CCI) by loosely ligating the sciatic nerve with 3
      ligatures, and allowed these mice to survive for a further 1, 2 or 3 weeks,
      during which time we assessed mechanoallodynia and thermal hyperalgesia. At the
      end of the testing period, the lumbar DRGs were removed for glyoxylic acid
      induced fluorescence of catecholamines to determine the extent to which
      sympathetic axons had invaded the DRG. We found that both indices of neuropathic
      pain were significantly attenuated in Wld mice compared to wild-type mice, with
      the wild-type mice increasing in sensitivity to both thermal and mechanical
      stimulation in the first week post-operative (PO), while Wld mice showed marked
      hypoalgesia following CCI. Histological examination of the DRG showed that
      sympathetic sprouting into the DRG was also markedly delayed in Wld mice compared
      to wild-type mice: 1 week following injury, sympathetic fibres had invaded the
      ipsilateral DRG of wild-type mice, while sprouting in ipsilateral DRG of Wld mice
      was only slightly increased at 3 weeks PO. These results show that Wallerian
      degeneration is tightly linked to the development of both pain and sympathetic
      sprouting following CCI, and we speculate on the possible role of NGF as a
      mediator of both phenomena.

PMID- 9272790
TI  - Dose ratio between morphine and hydromorphone in patients with cancer pain: a
      retrospective study.
AB  - Morphine (M) and hydromorphone (HM) are commonly used opioid analgesics for
      cancer pain. Opioid rotation is often necessary in the event of toxicity and/or
      inadequate analgesia. Equianalgesic reference tables based on single dose
      comparisons are possibly inadequate for patients on chronic treatment and
      developing tolerance. This retrospective study of opioid rotation involving M and
      HM sought to determine the equianalgesic dose ratio for 91 rotations in 74
      consecutively evaluable cancer pain patients. Only rotations involving
      subcutaneous (s.c.-s.c.) and oral (p.o.-p.o.) routes were evaluated. There were
      44 rotations from M-HM (34: s.c.-s.c., 10: p.o.-p.o.) and 47 rotations from HM-M
      (35: s.c.-s.c., 12: p.o.-p.o.). Expressing all ratios as M/HM, the median dose
      ratios (lower-upper quartiles) for s.c. and p.o. rotations were 4.92 (4.1-5.9)
      vs. 5.76 (4.9-5.8) for M-HM (P = 0.28, NS) and 4.0 (3.1-4.8) vs. 3.45 (2.8-4.2)
      for HM-M (P = 0.4, NS), respectively. Pain intensity, as measured on a visual
      analogue scale (VASP), showed no significant difference between mean values pre-
      and post-rotation. A unified overall median dose ratio of 4.29 (3.3-5.3, lower
      upper quartiles) was calculated by expressing all of the HM-M dose ratios as M/HM
      and combining them with the dose ratios for all of the M-HM rotations. This
      suggests a potency ratio of approximately 4.3:1 between M and HM. When expressed
      as M/HM for dose ratio comparison, the median dose ratio for all HM-M rotations
      was 3.7 (2.9-4.5, lower-upper quartiles) vs. 5 (4.2-5.9) for M-HM rotations (P =
      0.0001), suggesting that the opioid to which rotation is taking place is more
      potent than our proposed unified overall median dose ratio of 4.29:1 would
      predict. Our data suggests that HM is 5 times more potent than M when given
      second (M-HM), but is only 3.7 times more potent when given first (HM-M). We
      therefore recommend a ratio of 5 for M/HM in rotating from M to HM and ratio of
      3.7 for M/HM when rotating from HM to M in patients exposed to chronic dosing of
      these opioids. There was no correlation observed between M-HM and HM-M dose
      ratios and the level of previous opioid dose, in contrast to HM to methadone
      rotation where the dose ratio was higher in patients receiving higher doses of
      HM.

PMID- 9272791
TI  - The relationship of phantom limb pain to other phantom limb phenomena in upper
      extremity amputees.
AB  - In thirty-two unilateral upper extremity amputees with and without phantom limb
      pain, various phantom limb phenomena were investigated. In general, the incidence
      of non-painful phantom limb sensations was higher in patients with phantom limb
      pain than in pain-free amputees. Kinesthetic and kinetic phantom limb sensations
      were reported more frequently than exteroceptive cutaneous sensations. There was
      a significant positive correlation between phantom limb pain and stump pain.
      Patients more frequently assigned sensory than affective pain qualities to their
      phantom limb pain, whereas no differences between pain qualities were observed
      for stump pain. No support was found for a relationship between the presence of
      telescoping (i.e., shrinkage of the phantom limb) and phantom limb pain. These
      findings point to central as well as to peripheral factors contributing to
      phantom limb pain.

PMID- 9272792
TI  - The visual analogue pain intensity scale: what is moderate pain in millimetres?
AB  - One way to ensure adequate sensitivity for analgesic trials is to test the
      intervention on patients who have established pain of moderate to severe
      intensity. The usual criterion is at least moderate pain on a categorical pain
      intensity scale. When visual analogue scales (VAS) are the only pain measure in
      trials we need to know what point on a VAS represents moderate pain, so that
      these trials can be included in meta-analysis when baseline pain of at least
      moderate intensity is an inclusion criterion. To investigate this we used
      individual patient data from 1080 patients from randomised controlled trials of
      various analgesics. Baseline pain was measured using a 4-point categorical pain
      intensity scale and a pain intensity VAS under identical conditions. The
      distribution of the VAS scores was examined for 736 patients reporting moderate
      pain and for 344 reporting severe pain. The VAS scores corresponding to moderate
      or severe pain were also examined by gender. Baseline VAS scores recorded by
      patients reporting moderate pain were significantly different from those of
      patients reporting severe pain. Of the patients reporting moderate pain 85%
      scored over 30 mm on the corresponding VAS, with a mean score of 49 mm. For those
      reporting severe pain 85% scored over 54 mm with a mean score of 75 mm. There was
      no difference between the corresponding VAS scores of men and women. Our results
      indicate that if a patient records a baseline VAS score in excess of 30 mm they
      would probably have recorded at least moderate pain on a 4-point categorical
      scale.

PMID- 9272793
TI  - Ketamine, an NMDA receptor antagonist, suppresses spatial and temporal properties
      of burn-induced secondary hyperalgesia in man: a double-blind, cross-over
      comparison with morphine and placebo.
AB  - Effects of morphine and ketamine (NMDA receptor antagonist) on temporally
      summated pain ('wind-up-like pain') and spatial aspects of secondary hyperalgesia
      were investigated in 12 healthy volunteers. Hyperalgesia was produced by a local
      1 degree burn injury covering 12.5 cm2 on the medial surface of the calf. Primary
      hyperalgesia was determined by measuring heat pain detection threshold (HPDT)
      within the site of injury. Spatial aspects of secondary hyperalgesia present
      outside the site of injury were quantitated by determination of the areas in
      which a mechanical punctate (von Frey hair, 50.6 mN), or brush stimuli elicited
      pain sensation. Temporal aspects of secondary hyperalgesia were determined by
      repetitively pricking the skin with a standard von Frey hair (834 mN) inducing a
      'wind-up-like pain'. Morphine 0.15 mg/kg, ketamine 0.15 mg/kg or placebo (NaCl
      0.9%) were administrated i.v. on 3 separate days 50 min after the burn injury in
      a double-blind, placebo controlled, randomised and cross-over design. In all
      subjects HPDT was significantly reduced within the injured area compared to the
      pre-injury threshold (primary hyperalgesia). All subjects developed areas of
      allodynia and hyperalgesia to punctate stimuli and brush stimuli outside the
      injured area (secondary hyperalgesia). HPDT was not reduced in the area of
      secondary hyperalgesia. In 95% of the measurements we found a sudden appearance
      of pain to repeated pricking with a von Frey hair (834 mN) in the area of
      secondary hyperalgesia ('wind-up-like pain'). Ketamine significantly reduced the
      area of secondary hyperalgesia both for punctate and brush stimuli in the first
      measurement 15 min after injection and eight of the 11 subjects reported that the
      'wind-up-like pain' disappeared. On the measurements 45 and 75 min after ketamine
      injection, secondary hyperalgesia and 'wind-up-like pain' reappeared. Morphine
      did not significantly change the size of the area of secondary hyperalgesia and
      did not affect 'wind-up-like pain'. Ketamine or morphine did not change thermal
      detection thresholds. We conclude that spatial and temporal mechanisms,
      underlying secondary hyperalgesia, are mediated by glutamatergic transmission via
      NMDA receptors.

PMID- 9272794
TI  - Classical conditioning and the placebo effect.
AB  - Stimulus substitution models posit that placebo responses are due to pairings of
      conditional and unconditional stimuli. Expectancy theory maintains that
      conditioning trials produce placebo response expectancies, rather than placebo
      responses, and that the expectancies elicit the responses. We tested these
      opposing models by providing some participants with information intended to
      impede the formation of placebo expectancies during conditioning trials and by
      assessing placebo expectancies. Although conditioning trials significantly
      enhanced placebo responding, this effect was eliminated by adding expectancies to
      the regression equation, indicating that the effect of pairing trials on placebo
      response was mediated completely by expectancy. Verbal information reversed the
      effect of conditioning trials on both placebo expectancies and placebo responses,
      and the magnitude of the placebo effect increased significantly over 10
      extinction trials. These data disconfirm a stimulus substitution explanation and
      provide strong support for an expectancy interpretation of the conditioned
      placebo enhancement produced by these methods.

PMID- 9272795
TI  - Personality traits, pain duration and severity, functional impairment, and
      psychological distress in patients with persistent low back pain.
AB  - The relationships between psychological distress, pain duration, neuroticism,
      extraversion, pain severity, and functional impairment were examined in a large
      group of patients with persistent complaints of low back pain. We evaluated
      patients on a host of relevant variables before treatment and at 1 year and 2
      years after treatment which permitted assessment of the stability of the
      relationships over time. We found that the levels of psychological distress
      reported by patients were not related to the duration of their complaint. Rather,
      levels of psychological distress are related to both aspects of the patients'
      personalities, and characteristics of their illness. Patients who scored high on
      neuroticism reported higher levels of psychological distress than patients who
      scored low on this trait. Similarly, patients who had more severe pain and were
      more functionally impaired also reported higher levels of psychological distress
      due to pain. The relative strengths of these relationships varied with treatment
      status. Before treatment, psychological distress and neuroticism were strongly
      related, but after treatment, the relationship was moderate. In contrast, the
      relationship of psychological distress to pain severity and functional impairment
      was significantly strengthened after treatment. We attributed this shift in the
      relative strengths of the relationships to change in the patient perception of
      their illness.

PMID- 9272796
TI  - Inhibitory effects of electrically evoked activation of ventrolateral orbital
      cortex on the tail-flick reflex are mediated by periaqueductal gray in rats.
AB  - The present study found in lightly anesthetized rats that the radiant heat-evoked
      tail flick (TF) reflex was markedly inhibited by a unilateral electrical
      stimulation (a 20 ms train of 0.2 ms, 100 Hz, 30-100 microA pulses) of the
      ventrolateral orbital cortex (VLO), with the tail flick latency (TFL) being
      increased. The mean threshold of VLO stimulation for producing inhibition of the
      TF reflex was 39.2 +/- 8.7 microA (n = 26), and this inhibitory effect increased
      following increasing stimulation intensity from 40 to 70 microA. The inhibition
      developed and remained during the stimulation and disappeared rapidly after
      termination of the stimulation. When the VLO was stimulated at an intensity of
      100 microA in addition to the inhibition an after-facilitation of the TF reflex
      (a decrease in TFL) was observed at 5-10 s after termination of the stimulation.
      Bilateral electrolytic lesions of the lateral or ventrolateral parts of the
      periaqueductal gray matter (PAG) dramatically reduced or eliminated the VLO
      evoked inhibition, and the after-facilitation as well. The difference was
      significant between the TFL changes produced by VLO stimulation before and after
      PAG lesion (P < 0.01). The results suggest that the antinociception elicited by
      VLO stimulation is mediated by PAG, leading to activation of the brainstem
      descending inhibitory system which depresses the nociceptive transmission at the
      spinal level. The role played by VLO in pain modulation was discussed in
      association with the proposed endogenous analgesic system consisting of spinal
      cord-Sm-VLO-PAG-spinal cord.

PMID- 9272797
TI  - Pain and synovial fluid concentration of serotonin in arthritic temporomandibular
      joints.
AB  - The aim of this study was to investigate the relation between serotonin in the
      synovial fluid (SF-5-HT) and pain of arthritic temporomandibular joints (TMJ).
      The study comprised 1 male and 10 female patients (22 TM joints) with bilateral
      TMJ pain or tenderness and a mean age of 42 years. The patients were studied
      regarding pain from the TMJ at rest and during mandibular movements as well as
      regarding pressure pain thresholds and tolerance levels over the TMJ. TMJ
      samples, obtained by saline washing of the joint, and blood serum samples were
      taken for measurement of the 5-HT content. There was a positive correlation
      between SF-5-HT and pain in the TMJ upon movement. Maximum voluntary mouth
      opening ability was negatively correlated to SF-5-HT. In conclusion, the results
      of this study indicate that 5-HT in the TMJ synovial fluid is related to pain
      perceived upon movement of the joint and to decreased mandibular mobility.

PMID- 9272798
TI  - Right-hemisphere preponderance of responses to painful CO2 stimulation of the
      human nasal mucosa.
AB  - We recorded whole-scalp cerebral magnetic fields from healthy adults to painful
      CO2 pulses (duration 200 ms, concentration 65-90%), led to the left or right
      nostril once every 20 or 30 s. The stimuli were embedded in a continuous airflow
      (140 ml/s, 36.5 degrees C, relative humidity 80%) to prevent alterations in the
      mechanical and thermal conditions of the nasal mucosa. The recording passband was
      0.03-90 Hz and 16 single responses were averaged per run. Five out of the 9
      subjects showed replicable and artifact-free responses 280-400 ms after stimulus
      onset. The main responses originated close to the second somatosensory cortex
      (SII), most frequently in the right hemisphere, and also in the rolandic areas,
      mostly on the left. The signals were considerably stronger over the right than
      the left frontotemporal region, with a right-to-left ratio of 2.3 for areal mean
      signal amplitudes calculated across 16 channels, for both left and right nostril
      stimuli. Air puffs delivered to the nasal mucosa resulted in a trend for right
      hemisphere dominant responses, but responses to air puff stimulation of the lip
      and the forehead were symmetric. The right-hemisphere dominance of the SII
      responses may be associated with the painful, and thus unpleasant, nature of the
      CO2 stimulus, thereby suggesting involvement of the right hemisphere in
      emotional/motivational aspects of trigeminal pain, in agreement with the role of
      the trigeminal pathways as a general warning system.

PMID- 9272799
TI  - Opioid-mediated changes in nociceptive threshold during pregnancy and parturition
      in the sow.
AB  - This study aimed to investigate if pregnancy-induced hypoalgesia occurs in the
      sow, and to examine the role of endogenous opioids which are known to be released
      in response to nociception. Sixteen Large White x Landrace multiparous sows were
      tested in straw bedded pens (2.5 x 2.5 m) during weeks 4, 8 and 12 of pregnancy
      and over the farrowing period. Testing involved thermal stimulation of eight
      areas on the rear-quarters of the sows with a CO2 infra-red laser until a
      physical response was seen (tail flick, leg move or muscle twitch) or for a
      maximum of 16 s. Over the farrowing period testing was more frequent, and at 3.75
      h after the birth of the first piglet, half the sows received an injection (i.m.)
      of an opioid antagonist naloxone (N) (1 mg kg(-1) body weight) with the remainder
      receiving a control dose of saline (S). Responses were recorded 15 and 30 min
      post-injection. There was no significant difference between response times over
      weeks 4, 8 and 12 of pregnancy (P = 0.152), however a significant rise was seen
      from week 12 to 5 days before parturition (P = 0.002). Response times continued
      to rise until the birth of the first piglet by which time the majority of sows
      had stopped responding within 16 s (P < 0.001). Response times fell over days 1,
      2 and 7 post-partum. After administration of naloxone response times fell
      compared to control animals at 15 min (P < 0.001) and 30 min (P < 0.01) post
      injection. These results suggest that nociceptive threshold increases during late
      pregnancy in the sow, perhaps as an endogenous defence against labour pain, and
      that during parturition this change in nociceptive threshold is, at least in
      part, opioid-mediated. Oxytocin is known to be inhibited by endogenous opioids at
      parturition, thus future research should consider the potential role of increased
      nociception at birth as a negative feedback to oxytocin release.

PMID- 9272800
TI  - The expression of pain in infants and toddlers: developmental changes in facial
      action.
AB  - Age-related changes in the facial expression of pain during the first 18 months
      of life have important implications for our understanding of pain and pain
      assessment. We examined facial reactions video recorded during routine
      immunization injections in 75 infants stratified into 2-, 4-, 6-, 12-, and 18
      month age groups. Two facial coding systems differing in the amount of detail
      extracted were applied to the records. In addition, parents completed a brief
      questionnaire that assessed child temperament and provided background
      information. Parents' efforts to soothe the children also were described. While
      there were consistencies in facial displays over the age groups, there also were
      differences on both measures of facial activity, indicating systematic variation
      in the nature and severity of distress. The least pain was expressed by the 4
      month age group. Temperament was not related to the degree of pain expressed.
      Systematic variations in parental soothing behaviour indicated accommodation to
      the age of the child. Reasons for the differing patterns of facial activity are
      examined, with attention paid to the development of inhibitory mechanisms and the
      role of negative emotions such as anger and anxiety.

PMID- 9272801
TI  - The cortisol response to psychological stress in temporomandibular dysfunction.
AB  - The salivary cortisol response to psychological stress and its relationship to
      psychological variables was examined in 36 female temporomandibular dysfunction
      (TMD) sufferers and 39 female control participants. Saliva samples were taken at
      baseline, after completion of a modified version of the Trier Social Stress Test,
      and after rest. Participants also completed a battery of measures, including
      Visual Analog Scales for measuring pain intensity and disability and a number of
      established psychological scales. The TMD group showed a significantly higher
      cortisol response to experimental stress than the control group. Closer
      examination of the data revealed that the TMD group was heterogeneous and
      composed of a group that hypersecreted cortisol in response to stress (Hi-SC TMD
      group) and another group whose cortisol response was not significantly different
      from the control group (Lo-SC TMD group). The Lo-SC TMD group showed significant
      negative relationships between cortisol response and self-reported symptoms of
      both anxiety and depression, plus significantly more use of the Praying or Hoping
      coping strategy on the Coping Strategies Questionnaire. A dual relationship
      between TMD symptoms and the stress response is proposed. First, a biological
      predisposition to TMD is suggested by the stress response in the Hi-SC TMD group.
      Second, both psychological and biological variables appear to be important
      factors in those TMD patients who respond to stress with low cortisol secretion.

PMID- 9272802
TI  - Adrenosensitivity of injured afferent neurons does not require the presence of
      postganglionic sympathetic terminals.
AB  - Nerve injury sometimes triggers neuropathic pain states that are exacerbated by
      sympathetic efferent activity. A classic example is causalgia. The mechanism of
      coupling between sympathetic efferent activity and the afferent discharge
      responsible for pain sensation is a subject of controversy. Some authors hold to
      the 'direct coupling hypothesis' which proposes that noradrenaline (NA), released
      from sympathetic varicosities, acts directly on alpha-adrenoreceptors located in
      the membrane of injured primary afferents. Others believe that coupling is
      indirect; that the effects of NA are mediated by additional, non-adrenergic,
      chemical substances and their receptors (the 'indirect coupling hypothesis'). For
      example, it has been proposed that in inflamed skin NA acts back on the
      sympathetic endings which, secondarily, release a prostanoid mediator which
      sensitizes afferent endings. We report that the responsiveness of injured
      afferent axons to systemically applied NA persists, and in fact increases in
      prevalence, in rats that underwent prior chemical or surgical sympathectomy. The
      observation of adrenosensitivity in injured afferents in the absence of
      sympathetic postganglionic endings is consistent with the direct coupling
      hypothesis, which associates adrenosensitivity with the injured afferent axon. It
      is not consistent with the indirect coupling hypothesis which requires the
      presence of sympathetic endings as a source for NA-evoked prostanoid release.

PMID- 9272803
TI  - Effectiveness of oral sucrose and simulated rocking on pain response in preterm
      neonates.
AB  - Feeding and carrying have been interventions used by caregivers throughout
      history in relieving distress in infants. Recent studies on the food substance
      sucrose have elucidated the comforting effect of the taste component of feeding
      while studies of rocking have examined the comforting effect of the vestibular
      component of carrying. The purpose of this study was to determine the
      effectiveness of sucrose and simulated rocking alone and in combination on
      diminishing pain response in preterm neonates undergoing routine heelstick
      procedure in the neonatal intensive care unit (NICU). Preterm infants (n = 85)
      between 25-34 weeks post-conceptual age (PCA) and 2-10 days postnatal age (PNA)
      were randomly assigned to one of four conditions for routine heelstick procedure.
      The conditions were (1) sucrose alone: 0.05 ml of 24% sucrose was placed on the
      anterior surface of the tongue just prior to the lancing of the heel; (2)
      simulated rocking alone: 15 min prior to and during the heelstick procedure, the
      infant was swaddled and put on an oscillating mattress; (3) combination of
      sucrose and simulated rocking; and (4) placebo: 0.05 ml sterile water
      administered just prior to heelstick. Physiological (heart rate) and behavioural
      (facial actions) responses from baseline across 90 s following heelstick were
      scored second-to-second. Facial actions were analysed with repeated measures
      MANCOVA and heart rate with repeated measures ANCOVA. Behavioural state and
      gestational age were covariates. The groups that received sucrose alone or in
      combination with simulated rocking showed less facial actions indicative of pain
      than the rocking alone or control group. The addition of rocking to the sucrose
      condition tended to further blunt the facial expression of pain, but this
      enhancement did not reach a significant level. Heart rate was not decreased by
      any intervention compared to the control condition. Although the simulated
      rocking did promote quiet sleep, which has been reported in earlier studies to
      blunt pain response, there was no difference between simulated rocking and
      control groups in either facial expressions indicative of pain or heart rate. The
      implication of these results is that sucrose, but not simulated rocking may be a
      means of diminishing pain from minor procedures in preterm infants. Further
      research is needed on the use of sucrose for more than one procedure as well as
      examining the contact component of natural rocking, as opposed to simulated
      rocking.

PMID- 9272804
TI  - Episodic pain associated with a tumor in the parietal operculum: a case report
      and literature review.
AB  - We report a young woman suffering brief painful episodes in her right arm which
      sometimes spread to the whole right side of her body. The episodes were initially
      rare, but over 13 months they became increasingly frequent until occurring every
      20 min. Neurological examination was normal. Magnetic resonance imaging revealed
      a lesion in the white matter of the parietal operculum. Lesions in the parietal
      operculum associated with persisting thalamic pain or loss of pain sensation have
      been reported, but rarely with episodic pain. Since episodic painful attacks have
      been described in association with various suprathalamic lesions, we conclude
      that paroxysmal pain attacks may be another consequence of the disturbance of the
      normal pattern of thalamocortical connections to the second sensory cortical area
      by a lesion, in our case, of the subcortical area of the parietal operculum.

PMID- 9272805
TI  - Attention and somatic awareness in chronic pain.
AB  - Empirical methods are used to explore the relationship between chronic pain,
      somatic awareness and attention. Using a primary task paradigm, 46 chronic pain
      patients performed an attentionally demanding task. Patients were classified
      according to self reported pain intensity and the extent of their reporting of
      the perception of bodily sensations (somatic awareness). Results showed that, as
      predicted, disruption of attentional performance was most pronounced in those who
      reported high pain intensity and high somatic awareness. Further analysis
      revealed that these patients also reported high negative affect. These findings
      are discussed in terms of their theoretical implications for the concept of
      hypervigilance and their clinical implications for chronic pain control.

PMID- 9272807
TI  - Readiness to adopt a self-management approach to chronic pain: the Pain Stages of
      Change Questionnaire (PSOCQ).
AB  - This manuscript describes the development and initial validation of a self-report
      questionnaire designed to assess an individual's readiness to adopt a self
      management approach to their chronic pain condition. Theory and preliminary
      empirical work informed the development of a pool of items that were administered
      to a sample of individuals reporting chronic pain. Analyses of the data support a
      four factor measure that is consistent with the transtheoretical model of change
      and associated stages of change model. Each of the four factors,
      precontemplation, contemplation, action, and maintenance, was found to be
      internally consistent and stable over time. There was also substantial support
      for each factor's discriminant and criterion-related validity.

PMID- 9272806
TI  - Differences in patients' and family caregivers' perceptions of the pain
      experience influence patient and caregiver outcomes.
AB  - The purposes of this study were to determine if there were differences in pain
      intensity scores, pain duration scores, mood states, and quality of life of
      oncology outpatients whose pain intensity scores were congruent with their family
      caregivers compared to patients whose pain intensity scores were non-congruent
      and to determine if there were differences in mood states, health status, and
      caregiver strain between family caregivers whose pain intensity scores were
      congruent with their family members and those family caregivers whose pain
      intensity scores were non-congruent. A total of 78 patient-caregiver dyads
      participated in the study. Patients completed a Demographic Questionnaire, a
      Cancer Pain Questionnaire, the Profile of Mood States, and the Multidimensional
      Quality of Life Scale-Cancer 2. Family caregivers completed a demographic
      questionnaire, the Profile of Mood States, the Caregiver Strain Index, and the
      Medical Outcome Study Short-Form Health Survey. Both patients and family
      caregivers rated the patient's pain intensity using a visual analogue scale
      (VAS). Patients in the non-congruent dyads (i.e. difference of >10 on the VAS
      score) had significantly more mood disturbance and a poorer quality of life than
      patients in the congruent dyads. Family caregivers in the non-congruent dyads had
      significantly higher caregiver strain score than caregivers in the congruent
      dyads. These findings suggest that differences in the perception of the pain
      experience between patients and their family caregivers is associated with
      deleterious outcomes for the patient and their family caregivers.

PMID- 9272808
TI  - A comparison of pain report and adequacy of analgesic therapy in ambulatory AIDS
      patients with and without a history of substance abuse.
AB  - Concerns are often raised regarding the credibility of patients' report of pain
      and this concern is heightened among individuals with AIDS, where many patients
      have a history of injection drug use. This study compared the pain experience,
      adequacy of pain management and psychological well-being among patients with AIDS
      who reported a history of injection drug use (IDU) as their HIV transmission risk
      factor and patients with other HIV transmission risk factors. Five hundred and
      sixteen ambulatory AIDS patients participating in a quality of life study
      completed a series of self-report instruments including the Brief Pain Inventory,
      the Beck Depression Inventory, the Brief Symptom Inventory, the Functional Living
      Inventory and the Social Support Questionnaire. Results demonstrated that IDU and
      non-IDU subjects did not differ significantly in their report of pain prevalence,
      pain intensity or pain-related functional interference. However, IDU patients
      were significantly more likely to receive inadequate analgesic medications,
      reported lower levels of pain relief and a greater degree of psychological
      distress. There was also no difference in report of pain intensity, pain relief
      or functional interference among patients who acknowledged continued drug use,
      those who denied any recent drug use and patients participating in a methadone
      maintenance program. These data support the validity of AIDS patients' report of
      pain, at least in research settings, and suggest that undertreatment of pain is
      not restricted to patients who actively abuse drugs.

PMID- 9272809
TI  - Determinants of pain expression in hospitalized burn patients.
AB  - This study examines the relationship between extent of injury, degree and type of
      psychological distress and self-report of pain in burn survivors. One hundred
      eighty burn patients were interviewed within 2 weeks of their burn trauma. Using
      a visual analogue scale to assess subjective pain and pain relief, and self
      report measures of post-traumatic stress symptoms and general psychological
      distress, we assessed the relationship between PTSD symptoms, general distress
      and pain. Subjective pain was unrelated to sex, ethnicity, or total body surface
      area burned. The most important correlate of subjective pain was general
      psychological distress. Intrusive PTSD symptoms had no independent power to
      predict the variance in pain scores. However, among women, more severe avoidant
      symptoms were associated with greater subjective pain.

PMID- 9272810
TI  - Spinally administered dynorphin A produces long-lasting allodynia: involvement of
      NMDA but not opioid receptors.
AB  - The endogenous opioid peptide dynorphin A has non-opioid effects that can damage
      the spinal cord when given in high doses. Dynorphin has been shown to increase
      the receptive field size of spinal cord neurons and facilitate C-fiber-evoked
      reflexes. Furthermore, endogenous dynorphin levels increase following damage to
      the spinal cord, injury to peripheral nerves, or inflammation. In this study,
      sensory processing was characterized following a single, intrathecal injection of
      dynorphin A (1-17) in mice. A single intrathecal injection of dynorphin A (1-17)
      (3 nmol, i.t.) induced mechanical allodynia (hind paw, von Frey filaments)
      lasting 70 days, tactile allodynia (paint brush applied to flank) lasting 14
      days, and cold allodynia (acetone applied to the dorsal hind paw) lasting 7 days.
      Similarly, dynorphin A (2-17) (3 nmol, i.t.), a non-opioid peptide, induced cold
      and tactile allodynia analogous to that induced by dynorphin A (1-17), indicating
      the importance of non-opioid receptors. Pretreatment with the NMDA antagonists,
      MK-801 and LY235959, but not the opioid antagonist, naloxone, blocked the
      induction of allodynia. Post-treatment with MK-801 only transiently blocked the
      dynorphin-induced allodynia, suggesting the NMDA receptors may be involved in the
      maintenance of allodynia as well as its induction. We have induced a long-lasting
      state of allodynia and hyperalgesia by a single intrathecal injection of
      dynorphin A (1-17) in mice. The allodynia induced by dynorphin required NMDA
      receptors rather than opioid receptors. This result is consistent with results in
      rats and with signs of clinically observed neuropathic pain. This effect of
      exogenously administered dynorphin raises the possibility that increased levels
      of endogenous dynorphins associated with spinal cord injuries may participate in
      the genesis and maintenance of neuropathic pain.

PMID- 9272811
TI  - Loss of analgesic effect of morphine due to coadministration of rifampin.
AB  - Methadone withdrawal symptoms have been reported in drug addicts treated with the
      tuberculostatic rifampin. Whereas this interaction can be explained by induction
      of phase I drug metabolism (CYP3A4), knowledge about induction of phase II
      metabolism (e.g., UDP-glucuronosyltransferases = UGTs) and its influence on drug
      effects in man, however, is very limited. The potent analgesic morphine is
      metabolized by more than one UGT to the active metabolite morphine-6-glucuronide
      and to morphine-3-glucuronide, which is devoid of analgesic activity. Thus,
      differential induction of UGTs involved in metabolism of morphine might lead to
      decreased or increased analgesic effects, depending on which UGT is
      preferentially induced. We therefore investigated the influence of the potent
      enzyme inducer rifampin on analgesic effects and pharmacokinetics of morphine,
      which is primarily eliminated by phase II metabolism. Ten healthy male volunteers
      participated in this double-blind, placebo-controlled study with double crossover
      design. Morphine (10 mg p.o.) and placebo were administered on two separate
      occasions before and near the end of 13 days of treatment with rifampin (600
      mg/day). Blood samples were collected for 31 h. Morphine effects on pain
      sensation were determined using the cold pressor test. When morphine was given
      alone, the opioid elicited a significant increase in pain threshold and pain
      tolerance in comparison to placebo (P < or = 0.05). However, following
      administration of rifampin no analgesic effect of morphine was observed. In
      agreement, the area under the serum concentration-time curve (AUC) of morphine
      and the maximum serum concentration of morphine were considerably reduced during
      coadministration of rifampin (-27.7 +/- 19.3% and -40.7 +/- 27.1%; P < or =
      0.01). Moreover, during treatment with rifampin a proportional reduction of AUCs
      of morphine-3-glucuronide (P < or = 0.01), morphine-6-glucuronide (P < or = 0.05)
      and morphine was observed. Since urinary recoveries of both morphine-3
      glucuronide and morphine-6-glucuronide were also reduced during administration of
      rifampin, there is no evidence for a contribution of UGT induction to the
      observed interaction. In summary, a major drug interaction was observed between
      morphine and rifampin, which could not be attributed to induction of UGTs, but
      resulted in a complete loss of analgesic effects of the opioid.

PMID- 9272812
TI  - A model of transient hyperalgesia in the behaving monkey induced by topical
      application of capsaicin.
AB  - The aim of this study was to develop a model of transient hyperalgesia in the
      awake monkey performing operant tasks. An adult male rhesus monkey was trained to
      press a lever to receive food reward for detecting a light or to escape
      mechanical or thermal stimuli applied in the maxillary region of the face. A
      small contact thermode was positioned on one side of the face and a mechanical
      stimulator was placed on the other side. Noxious and innocuous thermal (43, 47
      and 51 degrees C) or mechanical (245, 490, 736 and 1472 mN) stimuli of 4.5-s
      duration were presented in a pseudo-random order. The animal was tested before, 1
      h and 24 h after topical capsaicin application (0.3 ml; 0.004 M). At the site of
      capsaicin application, the monkey escaped more thermal and mechanical stimuli 1 h
      after than before capsaicin, suggestive of thermal and mechanical hyperalgesia.
      At 24 h post-capsaicin, mechanical escape behavior had returned to baseline, but
      thermal escapes were still slightly elevated. Capsaicin had no significant effect
      on either mechanical or thermal escape behavior for stimuli presented to the
      contralateral site. Seven human subjects tested with these procedures reported
      higher pain intensity for similar stimuli after capsaicin application, in
      accordance with the monkey escape behavior. It is concluded that topical
      application of capsaicin on the maxillary face of the awake behaving monkey
      produces a transient thermal and mechanical hyperalgesia. The procedure is
      repeatable and produces no overt signs of distress. Thus it could provide an
      important tool for studying neural mechanisms of hyperalgesia and for testing
      analgesic treatments in primates.

PMID- 9272813
TI  - Neuropathic pain and prolonged regional inflammation as two distinct
      symptomatological components in complex regional pain syndrome with patchy
      osteoporosis--a pilot study.
AB  - To reappraise symptomatology of complex regional pain syndrome (CRPS), we
      investigated the clinical symptoms of seven patients with CRPS who showed
      associated patchy osteoporosis. The incidence of moderate to severe spontaneous
      pain, burning pain, mechanical allodynia was higher in patients with significant
      nerve injury than in those without. Periarticular tenderness adjacent to
      osteoporotic bones, abnormalities of blood flow, edema and impairment of motor
      function were seen in both groups of patients. Our clinical observations of
      patients with CRPS associated with patchy osteoporosis suggest that CRPS may have
      the following two distinct components: (1) neuropathic pain that includes severe
      spontaneous pain or severe persistent mechanical allodynia and (2) prolonged
      regional inflammation, the early phase of which could be indicated by positive
      inflammatory symptoms of pain (tenderness), heat, redness, swelling and loss of
      function and their alleviation with corticosteroids.

PMID- 9272814
TI  - Comments on Berkley, Pain 70 (1997) 103-107.

PMID- 9272815
TI  - Comments on Andersen et al., Pain, 67 (1996) 369.

PMID- 9272816
TI  - Comments on Ciccone et al., Pain, 68 (1996) 329-341.

PMID- 9272818
TI  - Comments on Cervero and Laird, Pain, 68 (1996) 13-23.

PMID- 9272817
TI  - Comments on Davar et al., Pain, 67 (1996) 135-139.

PMID- 9272820
TI  - Response to Stanton-Hicks et al.

PMID- 9272819
TI  - Reply to S.T. Meller: Ketamine: relief from chronic pain through actions at the
      NMDA receptor.

PMID- 9272821
TI  - Primum non nocere--a paradoxical ally in defense of placebos in analgesic trials?

PMID- 9272822
TI  - Autoradiographic characterization of [3H]cGMP binding sites in the rat brain.
AB  - Quantitative autoradiography was used to characterize and localize [3H]cGMP
      binding sites in the rat brain. [3H]cGMP binding was found to be pH-sensitive
      (with two optima at 7.4 and 5.0) and Mg2+-dependent. At pH 7.4, the binding was
      dependent on inclusion of the phosphodiesterase inhibitor IBMX. In contrast, at
      pH 5.0, IBMX had little effect on binding. The binding of [3H]cGMP was reversible
      and saturable with a Kd of 22 nM at pH 7.4 and 36 nM at pH 5.0. Bmax values were
      172 fmol/mg at pH 7.4 and 462 fmol/mg at pH 5.0. [3H]cGMP binding was inhibited
      by cGMP and its analogues, with cGMP and cAMP being the most potent at pH 7.4 and
      cGMP and 8-Br-cGMP being the most potent at pH 5.0. Using an extracellular pH 7.4
      buffer, the selective cGMP-dependent protein kinase (PKG) inhibitor Rp-8pCPT
      cGMPS had very little effect on [3H]cGMP binding. In contrast, with a cytosolic
      pH 5.0 buffer, Rp-8pCPT-cGMPS displaced binding in the cerebellum. This indicates
      that PKG is localized in the cerebellum, and that the binding to PKG is favored
      under cytosolic conditions. Autoradiographic localization of [3H]cGMP binding
      sites revealed a heterogeneous distribution with the highest densities in the
      substantia nigra and interpeduncular nucleus. High densities were also observed
      in the basal ganglia, the medial habenular nucleus, the frontoparietal cortex,
      the lateral amygdaloid nucleus and the subiculum. It is concluded that the nature
      of [3H]cGMP binding is complex, with one site probably being related to cytosolic
      PKG mainly found in the cerebellum, and one site probably representing cGMP
      stimulated phosphodiesterase mainly located in the forebrain.

PMID- 9272823
TI  - Potentiation of fentanyl suppression of the jaw-opening reflex by transcranial
      electrical stimulation.
AB  - Stinus et al. [L. Stinus, M. Auriacombe, J. Tignol, A. Limoge, M. Le Moal,
      Transcranial electrical stimulation with high frequency intermittent current
      (Limoge's) potentiates opiate-induced analgesia: blind studies, Pain, 42 (1990)
      351-363.] observed that transcranial electrical stimulation (TCES) with high
      frequency intermittent current potentiated opiate-induced analgesia using the
      tail-flick test. In unanesthetized, chronic preparations, electrical stimulation
      (0.5 Hz) of the lower incisor pulp of rats elicits a short-(6 ms) and a long
      latency (12-18 ms) jaw-opening reflex (JOR) without any evidence of aversive
      behavior [J. Azerad, F. Fuentes, I. Lendais, A. Limoge, B. Pollin, Methods for
      selective tooth pulp stimulation in acute and chronic preparations in rats, J.
      Physiol., 406 (1988) 3P.]. Fentanyl increases thresholds of both reflexes and
      transiently suppresses the long-latency JOR. We then decided to look at the
      influence of TCES on both drug-induced mean of maximal threshold variation (MMTV)
      and duration of JOR suppression period. These parameters have been investigated
      in 43 Wistar rats with or without TCES administered for 3 h before the drug
      injection and throughout the testing period. TCES alone has no effect. In
      contrast, it significantly increases the duration of the reflex suppression
      period (149 +/- 5% vs. control, P < 0.001) while fentanyl-increased reflex
      thresholds remain unchanged. The fentanyl-induced JOR suppression period returns
      to the control values 2 days later. When a second 3-h TCES session is delivered 2
      or 4 days after the first TCES session, a similar increase of this suppression
      period is observed. Moreover, 2 days after a second TCES session, an increase of
      the duration of the fentanyl-induced JOR suppression period is systematically
      observed. In contrast, a 6-h TCES session never induces such effects. These
      results confirm a potentiating effect of TCES on opioid action and demonstrate
      the value of repeated TCES sessions.

PMID- 9272824
TI  - Induction of c-fos gene expression by spinal cord transection in the rat.
AB  - Sympathetic nerve activity is maintained after high spinal injury through
      circuits that remain in question. We evaluated patterns of c-fos gene induction
      as a monitor of spinal neurons responding to high spinal cord transection in the
      rat. Rats were anesthetized with isofluorane. Lower cervical or upper thoracic
      spinal segments were exposed, immersed in warm mineral oil and transected. Spinal
      cords were exposed but not transected in anesthetized controls. After 2.5 h,
      spinalized and control rats were perfused for immunocytochemistry. Cervical and
      thoracolumbar spinal segments and dorsal root ganglia were sectioned coronally.
      Tissues were incubated in primary, polyclonal antisera raised in rabbit or sheep
      against a peptide sequence unique to the N-terminal domain of Fos, and processed
      immunocytochemically. Neurons were induced to express Fos-like immunoreactivity
      (FLI), bilaterally, in the spinal gray, but not in primary sensory ganglia.
      Spinal cord transection induced neurons to express FLI in thoracic laminae I, IIo
      (outer substantia gelatinosa), Vre (lateral reticulated division), VII (lamina
      intermedia) and X, and the intermediolateral cell column. Lamina VIII was also
      labeled in spinal-injured but not in control animals. Immunolabeled nuclei were
      prominent in lumbar segments and were concentrated in the medial third of laminae
      I and IIo, and in laminae VII and X. Few cells were labeled in upper cervical or
      sacral segments. FLI was sparse in the spinal gray of controls and expressed
      mainly within the dorsal root entry zone of upper thoracic segments. Patterns of
      c-fos gene expression were site-specific and correlated with laminae that respond
      predominantly to noxious stimulation and that contain sympathetic interneurons.
      Laminae that are responsive to non-noxious stimuli and activated by walking, IIi,
      nucleus proprius, medial V and layer VI were not induced to express FLI. We
      conclude that neurons in specific spinal laminae that process high threshold
      afferents and that harbor neurons with sympathetic nerve-related activity are
      activated selectively by spinal cord transections. We hypothesize that peripheral
      afferents processed by spinal-sympathetic circuit neurons may regulate
      sympathetic discharge in the absence of supraspinal drive.

PMID- 9272825
TI  - Most inspiratory neurons in the pre-Botzinger complex are suppressed during
      vomiting in dogs.
AB  - Pulmonary ventilation is almost completely suppressed during actual retching.
      Correspondingly, respiratory activity either disappears or changes to retching
      activity in peripheral respiratory nerves and respiratory neurons of the
      Botzinger complex and the caudal part of the ventral respiratory group. These
      results suggest the possibility that the respiratory rhythm generator is
      suppressed during retching. Recently, the pre-Botzinger complex (pre-BOT) has
      been postulated to generate respiratory rhythm. To evaluate this possibility, the
      activities of pre-BOT neurons were observed during fictive retching and expulsion
      in decerebrate paralyzed dogs. Inspiratory (I) neurons in the pre-BOT consisted
      of pre-, early-, late-, post- and throughout-subtypes, as in cats and rats.
      Inspiratory firing almost completely disappeared during fictive retching in about
      70% of the 158 pre-BOT I neurons examined, and changed to weak bursts produced
      either with retches or between retches in most of the remaining 30%. Similarly,
      all but one of the 21 I neurons examined did not produce any discharge with
      fictive expulsion. In contrast, all of the pre-BOT expiratory and inspiratory
      expiratory neurons examined produced vigorous bursts either with retches or
      between retches, and with expulsion. These results suggest that inspiratory
      outputs from the respiratory rhythm generator are almost completely suppressed
      during retching and expulsion, and that expiratory outputs change to retching and
      expulsion activities.

PMID- 9272826
TI  - Morphine blocks the bradycardia associated with severe hemorrhage in the
      anesthetized rat.
AB  - Progressive hemorrhage in the absence of tissue injury produces a biphasic
      response: an initial tachycardia, vasoconstriction and maintenance of arterial
      blood pressure by the baroreflex, followed by bradycardia, vasodilatation and
      hypotension due to the activation of a second 'depressor' reflex. The present
      study has investigated the effect of morphine (a mu-opioid receptor agonist) on
      the cardiac chronotropic response to a progressive hemorrhage at 2% total
      estimated blood volume (BV) min(-1) in the anesthetized rat. In control rats (20
      microl saline intracerebroventricularly, i.c.v.) heart period initially decreased
      significantly (P < 0.05) by a maximum of 5.4 +/- 0.8 ms from a baseline of 147.3
      +/- 2.2 ms after a blood loss of 8.3 +/- 1.5% BV, and then increased
      significantly by a maximum of 43.0 +/- 5.5 ms above the baseline after the loss
      of 34.5 +/- 1.6% BV. Blood pressure was initially maintained and then fell during
      the hemorrhage. The increase in heart period was prevented by treatment with
      morphine (10 microg i.c.v.), and the fall in blood pressure delayed
      significantly. These effects of morphine were prevented by pretreatment with
      naloxone (20 microg i.c.v.). Intravenous (i.v.) administration of morphine (10
      microg) had no effect on the response to hemorrhage. However, a clinically
      relevant dose of 0.5 mg x kg(-1) morphine (i.v.) abolished the bradycardia and
      delayed the fall in blood pressure associated with hemorrhage. These results
      indicate that morphine, acting on central nervous opioid receptors, can abolish
      the bradycardia and delay the hypotension associated with progressive hemorrhage,
      a pattern of response reminiscent of the effects of musculo-skeletal injury on
      the response to blood loss.

PMID- 9272827
TI  - Projections from the renal nerve to the cat's lateral somatosensory thalamus.
AB  - The representation of the kidney in the lateral somatosensory thalamus was mapped
      using electrical stimulation of the renal nerve in pentobarbitone-anesthetized
      cats. Ninety-five of 197 thalamic neurons studied responded to renal nerve
      stimulation. The responsive neurons were located in the periphery of the ventral
      posterolateral nucleus (42%; VPLp) and the neighboring dorsal and lateral aspects
      of the posterior complex (58%; POd and POl). No visceroceptive neurons were found
      within VPL proper. The mean response latency of the thalamic neurons to
      electrical nerve stimulation was 9.5 +/- 2.6 ms (mean +/- S.D.), suggesting an
      involvement of A delta, and possibly A beta fibers in the primary afferent
      pathway. The visceroceptive neurons were further characterized with innocuous
      mechanical stimulation of the body surface, and for 94 of the 95 neurons a
      somatic receptive field could be determined. Of these, 35% were located on the
      lower back and belly, i.e., the dermatomes of the lower thoracic and upper lumbar
      spinal projection areas of the renal nerve. 52% of the somatic receptive fields
      were located on the contralateral foot, thigh, tail, or hind leg (lower lumbar,
      sacral and coccygeal dermatomes) and 13% covered the arm and upper body (upper
      thoracic and lower cervical dermatomes). Comparison between the thalamic
      representations of the renal and pelvic nerves showed that both covered
      comparable areas adjacent and around, but not within VPL proper. It is concluded
      that VPLp, POd and POl play a role in processing visceral, possibly including
      nociceptive, information from the kidney of the cat.

PMID- 9272828
TI  - The locus coeruleus noradrenergic system in the rat brain studied by dual-probe
      microdialysis.
AB  - A dual-probe microdialysis technique was applied to the locus coeruleus (LC) and
      prefrontal cortex (PFC) of the brain of conscious rats. One probe was implanted
      close to the LC and was used to apply receptor-specific compounds by retrograde
      microdialysis. The effects of the LC infusions were recorded by a sampling
      noradrenaline by a second probe that was implanted in the ipsilateral prefrontal
      cortex. Infusion of sodium channel blocker tetrodotoxin (1 microM; 90 min) into
      the LC decreased extracellular noradrenaline in the PFC to approximately 20% of
      control values. Infusion of alpha2-adrenoceptor agonist clonidine (100 microM,
      infused during 15 or 45 min) near to the LC, decreased extracellular
      noradrenaline in the PFC to 35 and 20% of controls, respectively. These results
      indicate that > 80% of the extracellular levels of noradrenaline in the PFC is
      derived from LC innervation, and confirms the importance of alpha2-autoreceptors
      on noradrenergic neurons in the LC. Infusion of the cholinergic receptor agonist,
      carbachol (100 microM, 45 min) near to the LC increased extracellular
      noradrenaline in the PFC to approximately 150% of controls. Infusions of the
      excitatory amino-acid agonists NMDA and kainate into the LC caused marked
      increases in extracellular noradrenaline in the PFC to 240 and 200% of controls,
      respectively. The experiments with clonidine, carbachol, NMDA and kainate were
      repeated in anesthetized rats. Clonidine and carbachol were similarly effective
      as in conscious animals but the effects of NMDA and kainate on extracellular
      noradrenaline in the PFC were clearly suppressed: 145 and 130% of controls,
      respectively. These results suggest that increased arousal or behavioural
      activation might have contributed to the increases in extracellular noradrenaline
      that was seen after infusion of the glutamate agonists. These results also
      provide evidence for localization of cholinergic-, NMDA-, non-NMDA-receptor on
      noradrenergic neurons in the LC. Finally it is concluded that dual-probe
      microdialysis is a useful method to further investigate the pharmacology of LC
      noradrenergic neurons. Carbachol and clonidine are suitable tools for a rapid and
      reversible stimulation or inhibition, respectively, of noradrenergic LC neurons.

PMID- 9272830
TI  - Three-dimensional mapping of norepinephrine and serotonin in human thalamus.
AB  - Detailed quantitative information on catecholamines and 5-hydroxytryptamine
      (serotonin) in the human thalamus is much needed because of increasing interest
      in norepinephrine and serotonin as modulators of thalamic behavioral state
      control and overall information processing. This study provides three-dimensional
      distribution patterns of these monoamines in postmortem thalami from 13 normal
      subjects (no known neurological or psychiatric histories). The patterns come from
      a relatively fine-grained grid mapping procedure on successive coronal sections.
      Samples were analyzed by high performance liquid chromatography with
      electrochemical detection. The highest endogenous concentrations of
      norepinephrine are found in a ventromedial core that includes a number of the
      medial and intralaminar sub-nuclei but extends only slightly into the sensory
      regions of the lateral tier. The posterior portion of the thalamus, the pulvinar,
      contains low levels of norepinephrine. The distribution of 5-hydroxytryptamine is
      quite similar to that of norepinephrine in the rostral two-thirds of thalamus;
      however, in the pulvinar region, levels of serotonin are considerably increased
      and differ markedly between individual thalami. The study provides the first
      definitive mapping of serotonin levels in human thalamus. Consistent with many
      animal studies, there is no evidence for major dopaminergic innervation of human
      thalamus. By emphasizing the pattern distribution of the monoamines rather than
      the absolute values, it can be shown that the ambiguities of postmortem
      degradation frequently associated with biochemical assays are largely avoided.
      The terminal field distribution of norepinephrine is an essentially constant
      neurochemical signature in all thalami examined. The utility of the biochemical
      grid mapping procedure may be especially significant in terms of matching with
      data from functional neuroimaging techniques.

PMID- 9272829
TI  - Morphine- and anandamide-stimulated nitric oxide production inhibits presynaptic
      dopamine release.
AB  - Morphine and anandamide stimulate the release of nitric oxide (NO) in diverse
      tissues. The present study examines the consequences of this action on
      neurotransmitter release in ganglia from two invertebrates: ventral chain ganglia
      from the leech Hirudo medicinalis and the pedal ganglion from the mussel Mytilus
      edulis. In these ganglia, preloaded serotonin (5-HT) and dopamine (DA) can be
      released by 50 mM KCl. Anandamide, an endogenous cannabinoid substance,
      suppresses the potassium-stimulated release of [3H]DA (80%), but not 5-HT, in a
      concentration-dependent manner, from the neural tissues of both. The effect of
      anandamide can be antagonized by pre-exposing the neural tissues of both animals
      to SR 141716A, a potent cannabinoid receptor antagonist. Prior treatment of the
      ganglia with N-omega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide
      synthase inhibitor, significantly diminishes the inhibitory effect of anandamide.
      Morphine also inhibits [3H]DA release in a naloxone- and L-NAME-sensitive manner.
      Anandamide and morphine act through separate mechanisms since the respective
      antagonists show no cross-reactivity. The NO donor, SNAP, depressed the potassium
      stimulated release of preloaded [3H]DA, but not 5-HT, in the neural tissues of
      both animals. D-Ala2-Met5 enkephalinamide (DAMA) also inhibited the potassium
      stimulated release of [3H]DA in a naloxone-sensitive process. However, the effect
      of DAMA was seen in the presence of L-NAME (10(-4) M), indicating that the opioid
      peptide inhibition of the presynaptic release of DA is not coupled to NO. We
      postulate that cannabinoids and their endogenous effectors play a prominent role
      in the regulation of catecholamine release in invertebrates via NO release as is
      the case for opiate alkaloids.

PMID- 9272831
TI  - Calretinin in neurochemically well-defined cell populations of rabbit retina.
AB  - In the rabbit retina, parvalbumin has been localized selectively to AII amacrine
      cells, while 28 kDa calbindin could be detected in horizontal cells, in one type
      of depolarizing cone bipolar cell and a population of wide-field amacrine cells.
      The distribution of the third neuronal calcium binding protein, calretinin,
      however, has not been studied to date in detail in the rabbit retina. Therefore
      in this study we aimed to describe the overall distribution of calretinin in the
      different retinal layers and the possible colocalization pattern with other
      neurochemical marker molecules. A few cone photoreceptor cells were found to be
      labeled, whereas the outer plexiform layer was free from immunoreactive elements.
      In the most proximal row of the inner nuclear layer amacrine cells were labeled,
      while more distally a few cells emitted beaded axon-like processes toward the
      outer retina. There were large (18-28 microm in diameter) cells labeled in the
      ganglion cell layer, of which many apparently had their axon stained. Some of the
      calretinin immunoreactive amacrine cells (the AII neurons) also contained
      parvalbumin. Colocalization of calretinin and 28 kDa calbindin could not be
      ascertained in the same amacrine cell populations, nor was tyrosine hydroxylase
      present in calretinin-containing cells. There was partial colocalization of
      calretinin in the gamma-aminobutyric acid-positive amacrine cell population.
      Parvalbumin containing ganglion cells were also positive for calretinin; however,
      the calretinin-positive ganglion cells were more numerous. gamma-Aminobutyric
      acid could be colocalized in some calretinin-positive neurons of the ganglion
      cell layer.

PMID- 9272832
TI  - Strain differences in pentylenetetrazol-kindling development and subsequent
      potentiation effects.
AB  - Rats from two different strains, i.e. Wistar rats and Lister hooded rats, were
      investigated for their ability to acquire the kindling syndrome. After having
      received 13 kindling stimulations (injection of pentylenetetrazol), the animals
      were tested for subsequent alterations in induction and maintenance of
      hippocampal long-term potentiation (LTP) and, moreover in glutamate binding. It
      was found that rats from both strains did not differ in the response to the
      initial injection of pentylenetetrazol (PTZ) and the amplitude of the population
      spike. This suggests that some aspects of basic central excitability are
      equivalent. Wistar rats acquired the kindling syndrome rapidly whereas seizure
      outcome was poor in Lister rats. As regards hippocampal LTP, the population spike
      was only dramatically increased in Wistar rats after kindling completion.
      Glutamate binding was not altered in animals from the Lister strain. The results
      suggest that changes in glutamate binding and the increase in the population
      spike are characteristic consequences of kindling.

PMID- 9272833
TI  - Evidence for CCK(A) receptor involvement in the acquisition of conditioned
      activity produced by cocaine in rats.
AB  - Cholecystokinin (CCK) is co-localized with dopamine (DA) in the nucleus accumbens
      (NAC) where evidence suggests that CCK(B) receptor-mediated mechanisms inhibit,
      while CCK(A) receptor-mediated mechanisms facilitate, DA function. As DA has been
      implicated in the acquisition of conditioned activity, the present experiments
      investigated the effects of CCK(A) and CCK(B) receptor selective antagonists on
      the acquisition and expression of conditioned activity produced by cocaine.
      Paired rats received four cocaine-environment pairings whereas Unpaired rats
      received the two stimuli explicitly unpaired, in that they received cocaine in
      the home cage. Using this procedure, cocaine (10 mg/kg, i.p.) reliably produced
      conditioned activity such that the Paired group showed a higher level of
      locomotion than the Unpaired group on a subsequent drug-free test day. Systemic
      administration of devazepide, a CCK(A) receptor antagonist, but not L-365,260, a
      CCK(B) receptor antagonist, blocked the acquisition of conditioned activity.
      Microinjection of the CCK(A) antagonist PD-140548 into the NAC similarly impaired
      the acquisition of conditioned activity. However, systemic administration of
      neither the CCK(A) nor CCK(B) receptor antagonist modified the expression of
      cocaine-induced conditioned activity once established. These studies suggest that
      CCK(A), but not CCK(B), receptor mediated mechanisms in the NAC play a key role
      in the acquisition of conditioned activity.

PMID- 9272834
TI  - Marked alterations in the cellular localisation and levels of apolipoprotein E
      following acute subdural haematoma in rat.
AB  - Apolipoprotein E (apoE) plays a role in the response to acute brain injury, the
      mechanisms as yet remain unknown. In the present study, alterations in the
      immunohistochemical localisation of apoE in rat cortex were examined at 30 min, 2
      h or 4 h following production of an acute subdural haematoma. Levels of apoE were
      determined in cortex by immunoblotting at 30 min and 4 h post-haematoma.
      Extensive areas of ischaemic cell damage were observed in the cortex underlying
      the haematoma with minimal damage observed in shams. In sham animals, apoE
      immunoreactivity was confined to astrocytes and their processes. Following the
      haematoma induction, apoE immunoreactivity was dramatically altered. At 30 min
      post-haematoma, intense apoE staining was observed in clusters of neuronal
      perikarya and the neuropil throughout the cortical layers underlying the
      haematoma and this persisted at 2 h and 4 h post-haematoma. Additionally, at 4 h
      post-haematoma marked apoE staining of discrete foci within the neuropil closely
      associated with capillaries was consistently observed in the ipsilateral cortex.
      Immunoblotting indicated there were no significant alterations in the cortical
      levels of apoE at 30 min post-haematoma but, at 4 h post-haematoma, there was a
      significant elevation (27%, P < 0.001) in the levels of apoE in cortex underlying
      the haematoma compared to control levels. The results indicate that following
      acute subdural haematoma, a rapid cellular redistribution of apoE occurs and
      precedes a significant elevation in the levels of apoE. These alterations in apoE
      may occur, at least initially, as part of the brain's protective response to
      injury.

PMID- 9272835
TI  - Cyclic AMP endogenously enhances synaptic strength of developing glutamatergic
      synapses in serum-free microcultures of rat hippocampal neurons.
AB  - The time course of development of autaptic and synaptic connections and the
      contribution of endogenously activated cAMP signaling to the regulation of
      AMPA/kainate receptor-mediated synaptic transmission were studied in
      microcultures of isolated single hippocampal neurons or of pairs of neurons grown
      on astrocytic islands in serum-free culture medium. Standard whole cell patch
      clamp techniques were employed to monitor evoked and spontaneous autaptic and
      synaptic currents. Glutamatergic synaptic transmission became detectable after 4
      days in vitro (DIV). After 9-10 DIV more than 80% of the neurons had developed
      glutamatergic autaptic and synaptic connections. Elevation of intracellular cAMP
      levels by application of forskolin (20 microM) or IBMX (200 microM) to autaptic
      neurons resulted in enhanced autaptic current amplitudes (forskolin: 146 +/- 9%,
      IBMX: 177 +/- 21% of control) and impaired paired pulse facilitation (PPF).
      Likewise, intracellular application of cAMP via the patch pipette into autaptic
      neurons or into the presynaptic neuron of a synaptically connected pair also
      resulted in enhanced autaptic/synaptic current amplitudes (170 +/- 16% of
      control). In contrast, injection of cAMP into the postsynaptic neuron of a
      synaptic pair failed to significantly enhance the synaptic responses. The
      magnitude of the cAMP-mediated enhancement depended on the initial
      autaptic/synaptic strength observed in an individual cell, with small
      autapses/synapses being enhanced more effectively. Application of an inhibitor of
      cAMP-mediated processes (Rp-cAMPS) reversibly reduced autaptic/synaptic current
      amplitudes (to 75 +/- 5% of control). Taken together, these results suggest that
      cAMP-mediated processes endogenously enhance the efficacy of developing
      glutamatergic autaptic and synaptic connections in serum-free microcultures of
      isolated hippocampal neurons.

PMID- 9272836
TI  - Colocalization of GABA(A) and NMDA receptors within the dorsal motor nucleus of
      the vagus nerve (DMV) of the rat.
AB  - Changes in gastric motor activity are observed in response to glutamate and GABA
      in the DMV. We investigated the expression of GABA(A) and NMDA receptors within
      DMV neurons projecting to the stomach using pseudorabies virus (PRV). PRV
      immunoreactive (PRV-IR) cells expressing GABA(A) alpha1-IR, also expressed NMDAR1
      suggesting that NMDA and GABA(A) receptors are colocalized. These results provide
      a neuroanatomical basis for these receptors jointly playing a role in gastric
      motor functions.

PMID- 9272837
TI  - Long-term potentiation persistence greater in C57BL/6 than DBA/2 mice: predicted
      on basis of protein kinase C levels and learning performance.
AB  - The gamma isoform of protein kinase C (gamma-PKC) activity is elevated and
      learning is superior in the inbred C57BL/6 mouse when compared to the DBA/2 mouse
      strain. Given the proposed link between PKC and long-term potentiation (LTP) on
      the one hand and PKC and learning on the other, it was predicted that LTP
      persistence would be greater in C57BL/6 mouse. When suprathreshold levels of
      tetanic stimulation were used, similar persistent LTP was observed in both
      C57BL/6 and DBA/2 strains. However, when tetanus was at threshold, the response
      in DBA/2 mice decayed to baseline in 30 min, similar to short-term potentiation
      (STP). Using this same paradigm with C57BL/6 mice, LTP persisted for 4 h, the
      longest time tested. The time course of the results parallels those observed in
      rat when phorbol ester, a potent PKC activator, converts STP to LTP. The present
      findings thus confirm the predicted difference between the two mouse strains.
      Moreover, the present findings are consistent with a role for gamma-PKC in LTP.
      Since such results call attention to the need for gamma-PKC interventive
      procedures, the relative utility of current PKC inhibitors, null mutants and
      antisense methods are discussed.

PMID- 9272838
TI  - Prothoracicotropic hormone-producing neurosecretory cells in the silkworm, Bombyx
      mori, express a muscarinic acetylcholine receptor.
AB  - Using an anti-muscarinic acetylcholine receptor (mAChR) antibody and an anti
      prothoracicotropic hormone (PTTH) antibody, double immunofluorescence staining
      was performed on brain sections of the silkworm, Bombyx mori. Four pairs of
      dorsolateral neurosecretory cells, along with some intercerebral neurosecretory
      cells, were immunoreactive to anti-mAChR antibody. Among these immunoreactive
      cells, two pairs of dorsolateral neurosecretory cells were identified to be PTTH
      producing neurosecretory cells. Nerve fibers in the median and paramedian
      protocerebral areas, and nerve terminals in the corpus allatum also showed
      immunoreactivity to the anti-mAChR antibody. Some of these nerve terminals
      expressing mAChRs were overlapped by immunostaining with the anti-PTTH antibody.
      These results indicated that PTTH-producing neurosecretory cells of Bombyx mori
      expressed an mAChR, and that muscarinic, cholinergic transmission might directly
      regulate PTTH release from neurosecretory cells.

PMID- 9272839
TI  - Desensitization of Fos protein induction in rat striatum and nucleus accumbens
      following repeated administration of delta9-tetrahydrocannabinol.
AB  - The purpose of the present study was to clarify the effect of repeated
      administration of delta9-tetrahydrocannabinol (THC) on Fos protein induction in
      the rat brain. Pretreatment of rats for 3 days with THC (10 mg/kg, i.p.)
      attenuated the effect of THC (10 mg/kg) to induce the expression of Fos protein
      in rat striatum and nucleus accumbens. This desensitization of Fos protein
      induction might explain the rapid development of behavioral tolerance to repeated
      administration of THC.

PMID- 9272840
TI  - Schwann cells can misdirect regrowing neuronal processes.
AB  - Studies of potentials for dorsal spinal nerve root axons to regrow into the
      spinal cord involved placement of the tracer HRP/WGA-HRP on the cut end of the
      nerve root. Following this procedure, labeled neurons were found within the
      spinal dorsal gray matter. Analyses revealed that spinal neurons influenced by
      the presence of radiation-induced intraspinal Schwann cells extend misdirected
      processes into the dorsal root.

PMID- 9272841
TI  - The Amsterdam Growth and Health Longitudinal Study. The past (1976-1996) and
      future (1997-?).
AB  - This article presents an overview of the Amsterdam Growth and Health Longitudinal
      Study (AGAHLS). This study was started in the 1970s, following a whole sample of
      500 healthy 13-year-old boys and girls from two secondary schools. During the
      school period (12-17 years) annual measurements were performed with respect to
      anthropometrics, physiological and psychological parameters, lifestyle
      characteristics (activity, diet, smoking) and health parameters. A multiple
      longitudinal design was applied with overlapping birth cohorts and a cross
      sectional measured control group to monitor for confounding factors such as time
      of measurement, cohort, dropout and testing effects. Emphasis is also placed on
      measures that enhance adherence of the subjects. The follow-up was extended with
      repeated measurements at age 21, 26 and 28. This enabled us to analyze the data
      with respect to tracking characteristics of biological and lifestyle variables
      over a period of 15 years between adolescence and adulthood and also to
      investigate quasi-causal relationships between the effects of a healthy lifestyle
      and indicators for cardiovascular diseases (CVD). Also new methods such as
      measurement of atherosclerosis and osteoporosis will be added and related to
      longitudinal measurements of the same subjects in the past. The main results that
      were obtained in the past are summarized and research questions for the near
      future are explained.

PMID- 9272842
TI  - Opportunities and difficulties in long-term studies of growth.
AB  - Overviews are presented of the University of Melbourne Child Growth Study and of
      the Fels Longitudinal Study; each of these studies had a major focus on the
      growth and maturation of children. Planning, study design, logistics and staffing
      varied between these studies, but each led to exciting research opportunities
      that can exist only when longitudinal data are available. There are important
      differences between these studies in the types of participants, ages at
      examinations, the variables measured, some topics of central concern, and in
      funding. In each study, research productivity was low in the early years, the
      retention of participants was a major concern, and it was necessary to maintain a
      balance between data collection, data management, and data analysis. More such
      studies are needed that focus on particular population groups and topic areas and
      that utilize the lessons of the past to maximize the chances of future success.

PMID- 9272843
TI  - Weight, weight gain, activity, and major illnesses: the Nurses' Health Study.
AB  - The Nurses' Health Study was initiated in 1976 to study the relation between oral
      contraceptives and breast cancer. Subsequent funding was available to follow the
      cohort to address relations between cigarette smoking, postmenopausal hormones,
      hair dyes, and a range of cancers including breast, endometrial, ovarian, and
      lung cancer. The 121,700 participating nurses are followed up every 2 years via
      mail questionnaire to update exposure information to identify incident cancers
      and other illnesses. Follow-up through 1994 has achieved 90% response from living
      cohort members. Over the course of the study, additional exposures have been
      added and refined, including weight at age 18, current weight, height, waist and
      hip measurements and history of major voluntary weight loss among others. Our
      focus has been on the health effects of weight gain during middle age. The
      results relating to diabetes, coronary heart disease, certain types of cancer and
      total mortality are reviewed. Our primary analytic tools have been multiple
      logistic regression and Cox proportional hazards models. These methods allow for
      flexibility in defining the exposures of interest as well as determining their
      relative importance while controlling for key risk factors. Our models show that
      even moderate weight gain after age 18 increases risk of each condition. The
      benefits of physical activity include reduced risk of disease. Issues in the
      measurement and validation of weight and activity highlight the complexities that
      are inherent in observational studies addressing the health consequences of
      lifestyles and anthropometric variables. Our experience of working with repeated
      measures of body weight and recreational activity are described. Recreational
      activity has been ascertained in various ways on several questionnaires and may
      be subject to misclassification. For both weight and activity it may be the
      pattern of these values that is of importance (e.g. "weight cycling") for some
      outcomes or conditions. Our research in this area is ongoing. These issues
      regarding longitudinal measurement will never be completely resolved because
      weight and activity are intrinsically complex concepts. For these and other such
      variables, the primary solution is to minimize the problems associated with
      longitudinal studies. This is best accomplished by developing and maintaining a
      very strong study design/protocol, including: careful consideration of the sample
      frame and sample size; maintenance of a high response rate; and continuous
      monitoring and improvement of the survey/interview instrument(s).

PMID- 9272844
TI  - Development and tracking in fitness components: Leuven longtudinal study on
      lifestyle, fitness and health.
AB  - In the Leuven Growth Study of Belgian Boys the growth and physical performance of
      Belgian boys followed longitudinally between 12 and 19 years were studied.
      Subsequently, a subsample (n = 240) of Flemish-speaking males were reexamined at
      30 and 35 years. A first question relates to the individual growth patterns in a
      variety of physical fitness characteristics. The three strength tests (static,
      functional, explosive) show curves that are qualitatively similar to those for
      height and weight. Their adolescent spurts occur after the height spurt.
      Flexibility and the two speed tests appear to reach maximum velocities prior to
      the height and weight spurts. Longitudinal principal component analysis was
      applied to the study of growth patterns of several somatic and motor
      characteristics. The results for height show three components sufficient to
      provide an adequate representation of the original information. The first
      component characterizes the general position of an individual growth curve.
      Components 2 and 3 reflect fluctuation in percentile level during the age period
      studied and can be conceived as indices of stability and are related to age at
      peak height velocity (APHV) and peak height velocity (PHV), respectively.
      Relationships between somatic characteristics, physical performance, and APHV
      have been studied in a sample of 173 Flemish boys, measured yearly between +/- 13
      and +/- 18 years and again as adults at 30 years of age. The sample was divided
      into three contrasting maturity categories based on the APHV. There are
      consistent differences among boys of contrasting maturity status during
      adolescence in body weight, skeletal lengths and breadths, circumferences, and
      skinfolds on the trunk. There are no differences in skinfolds on the extremities.
      None of the differences in somatic dimensions and ratios among the three
      contrasting maturity groups are significant at 30 years of age except those for
      subscapular skinfold and the trunk/extremity skinfold ratio. During adolescence,
      speed of limb movement, explosive strength and static strength are negatively
      related to APHV; thus, early maturers performed better than late maturers.
      However, between late adolescence and adulthood (30 years), the late maturers not
      only caught up to the early maturers, but there were significant differences for
      explosive strength and functional strength in favor of late maturers. Finally,
      age-specific tracking, using inter-age correlations, of adult health- and
      performance-related fitness scores were investigated. In addition, the
      independent contribution of adolescent physical characteristics to the
      explanation of adult fitness scores was also studied. Tracking between age 13 and
      age 30 years was moderately high (46% of variance explained) for flexibility, low
      to moderate (between 19% and 27% of variance explained) for the other fitness
      parameters and low for pulse recovery and static strength (7% to 11% of variance
      explained). Between age 18 and age 30 years the tracking was high for
      flexibility, moderately high for explosive and static strength, and moderate for
      the other fitness parameters except for pulse recovery. The amount of variance of
      adult fitness levels explained increased significantly when other characteristics
      observed during adolescence entered the regressions or discriminant functions.

PMID- 9272845
TI  - Prospective and retrospective longitudinal studies of the growth, maturation, and
      fitness of Polish youth active in sport.
AB  - Results of three longitudinal studies of the growth, maturation and fitness of
      youth active in sport are summarized. Data include size attained and growth rates
      for height and body mass, secondary sex characteristics, skeletal age, age at
      peak height velocity, and two indicators of fitness, peak O2 uptake and power
      output at a heart rate of 170 bpm (PWC 170). The data for active youth are
      compared to local reference data and where appropriate to data from other
      European longitudinal studies. Allowing for variation in methodology and
      sampling, regular training in sport during puberty and the adolescent spurt does
      not influence size attained, growth rate, and the timing and progression of
      somatic, sexual and skeletal maturation in boys and girls. Active and nonactive
      boys and girls, respectively, do not differ significantly in the mean age at
      maximum growth in power output at a heart rate of 170 bpm. Boys active in sport,
      however, have a greater maximal gain in submaximal power output than nonactive
      boys. Analysis of ontogenetic allometry of peak oxygen uptake and stature and
      body mass indicate variation between individuals, and between boys of contrasting
      maturity status.

PMID- 9272846
TI  - Analysis of cohort effects in mixed longitudinal data sets.
AB  - Mixed longitudinal designs are among the most efficient for the study of growth
      and developmental processes. In this approach, one studies several (birth)
      cohorts, each for a relatively short length of time, and then links the growth
      curves for the individual cohorts together to obtain the growth curve for the
      entire length of time spanned by the ages of the subjects in all cohorts. Thus,
      e.g., in the Nijmegen Growth Study, three cohorts were each studied for 5 years,
      the intent being to join the three curves together to form a single curve
      covering the entire period from 4 to 14 years of age. In order for this approach
      to be valid, there either should be no cohort effects (secular trends) or the
      fitted curve must be adjusted in some way to correct for such effects if they
      exist. The question thus arises as to how one should test for the presence of
      cohort effects and what one should do about them if found. The problems which may
      arise using height and weight data from the Nijmegen Growth Study are
      illustrated. In particular for girls, height and weight both show cohort effects
      (at 9.25 years of age) when the raw data are used. If, however, the observed data
      are used to estimate the values at the target age, and these values are used in
      the comparison, differences between the cohorts are no longer significant. The
      problems are further illustrated using data from a mixed longitudinal data set of
      cleft lip and palate patients and data from the National Dutch Growth Study 1980.

PMID- 9272847
TI  - The Saskatchewan Pediatric Bone Mineral Accrual Study: bone mineral acquisition
      during the growing years.
AB  - To investigate bone mineral accretion in growing children, the Saskatchewan
      Pediatric Bone Mineral Accrual Study was initiated in 1991. The study involves
      the collection of dietary and physical activity information along with
      anthropometric growth and maturity measurements every 6 months and dual-energy X
      ray absorptiometer (DXA) bone scans of the whole body, AP lumbar spine and
      proximal femur taken annually. The study has now finished its 6th year and 68
      males and 72 females from an original sample of 228 elementary schoolchildren are
      still involved. To investigate how bone mineral at clinically important sites
      proceeds in relation to maturation we developed distance and velocity growth
      curves for height and bone mineral content (BMC) for the AP lumbar spine, the
      femoral neck and the whole body. In both boys and girls, over 35% of total body
      and AP spine bone mineral and over 27% of the bone mineral at the femoral neck
      was laid down during the 4-year adolescent period surrounding peak linear growth
      velocity. The clinical significance of these values can be appreciated by
      consideration of the fact that as much bone mineral will be laid down during
      these 4 adolescent growing years as most people will lose during all of adult
      life.

PMID- 9272848
TI  - The SENECA study: potentials and problems in assessing dietary changes over time.
AB  - In 1988 a European multicenter study, named SENECA, was initiated. Nine of the
      original 19 participating towns in 12 European countries decided to continue the
      longitudinal study by conducting a second survey in 1993. The aim of the
      longitudinal part of the SENECA study was to provide measurements of diet,
      lifestyle, health and performance as such at two points in time and to analyze
      the direction of changes and possible interrelationships between the factors
      studied. For the present paper the experience with the SENECA study has been used
      to illustrate the problems related to nutritional longitudinal studies in
      different stages of dietary research. In the examples we have focused on results
      relating changes in body weight to energy intake and changes in total cholesterol
      to intakes of fat and fatty acids of participants from four SENECA sites. To
      examine dietary habits a modified dietary history was chosen consisting of two
      parts: an estimated record and a checklist of foods. The results demonstrate that
      the special design of the study and adaptation of methods made it possible to
      deal with several problems encountered in nutritional longitudinal studies in
      elderly people. Nevertheless the changes in diet are most likely underestimated.
      Consequently in the interpretation of data and further analysis we have to
      consider this problem as well as other remaining problems.

PMID- 9272849
TI  - Physical activity and health of college men: longitudinal observations.
AB  - The College Alumni Health Study has examined host and environmental
      characteristics in youth and adult life as they relate to subsequent development
      of specific chronic diseases. Campus archives have provided physical,
      psychological, and social data on some 57,500 men and women who were born between
      1896 and 1934, and who entered Harvard College or the University of Pennsylvania
      between 1916 and 1950, generally at age 17-20 years. These college data have been
      studied subsequently to assess whether characteristics in youth predisposed
      students to chronic diseases (nonfatal and fatal) later in life. Follow-up
      questionnaires, mailed to alumni, generally aged 35-85 years, in the 1960s,
      1970s, 1980s, and 1990s have provided mid-life information on the health status
      and health habits of survivors, and official death certificates have provided
      data on decedents. This information has been studied, in fashion similar to the
      college data, for personal characteristics and ways of living that influenced
      health and longevity of these middle-aged and elderly men. Longitudinal
      observations continue today, in search of causes of specific chronic diseases.

PMID- 9272850
TI  - Limitations of growth charts derived from longitudinal studies: the Euro-Growth
      Study.
AB  - Length and weight for age (1-12 months) charts are presented for the longitudinal
      Euro-Growth Study. "Weight-for-length", another widely used growth chart,
      presents a problem from a methodological point of view. Target length values (53
      77 cm) are not observed in all infants, leading to truncated age distributions at
      most target lengths. It was demonstrated that the age at which the target length
      was reached (Fig. 8) had a significant influence on weight especially at a
      smaller length. This implies that the weight-for-length charts are biased. This
      phenomenon is due to the longitudinal measurement schedule at prechosen ages and
      not at prechosen lengths, which is impossible. To obtain the desired length
      corrected weight standards, it is advocated to construct age-related body mass
      indices.

PMID- 9272852
TI  - Different statistical models to analyze epidemiological observational
      longitudinal data: an example from the Amsterdam Growth and Health Study.
AB  - With the development of new statistical techniques [such as generalized
      estimating equations (GEE)] it became possible to analyze longitudinal
      epidemiological relations, using all available longitudinal data. However, there
      are different possibilities in modeling longitudinal relations. In this paper
      four possible models were compared. (1) A simple model in which the actual values
      of the outcome and predictor variables were related (Y(it) = beta0 +
      beta1X(it)...); (2) A model with a time lag between outcome and predictor
      variables (Y(it) = beta0 + beta1X(it-1)...); (3) A model in which not the actual
      values, but changes in values between different time points were related ([Y(it)
      Y(it-1)] = beta0 + beta1 [X(it)-X(it-1)]...); and (4) A first-order
      autoregressive model in which the actual value of the outcome variable at time
      point t is not only related to the actual value of the predictor variable at time
      point t, but also to the value of the outcome variable at t-1 (Y(it) = beta0 +
      beta1X(it) + beta2Y(it-1) +...). In this paper the use of the possible models was
      discussed by means of an example with data from the Amsterdam Growth and Health
      Study. In this longitudinal observational study six repeated measurements were
      carried out over a period of 15 years on subjects with an initial age of 13
      years. It can be concluded that each model reflects different parts of the
      longitudinal relationships and the choice for a particular model must be based on
      logical considerations. However, in most cases epidemiologists should use the
      results of different models to obtain a more accurate answer to the particular
      epidemiological question.

PMID- 9272851
TI  - Leisure time physical activity and the 16-year risks of mortality from coronary
      heart disease and all-causes in the Multiple Risk Factor Intervention Trial
      (MRFIT).
AB  - PURPOSE: To examine the long-term association of leisure time physical activity
      (LTPA) and risk of death from coronary heart disease (CHD) and all-causes.
      METHODS: Data are from a prospective study of 12,138 middle-aged men at high risk
      for CHD participating in the MRFIT. Men were classified into deciles based on
      average min/d of LTPA reported at baseline, which were compared with cumulative
      CHD and all-cause mortality endpoints at the 16-year follow-up. RESULTS: Men in
      the least-active decile of LTPA who averaged 4.9 min/d of LTPA (range 0 to .9
      min/d) had excess age-adjusted mortality rates of 29% and 22% for CHD and all
      causes, respectively, as compared to those in combined deciles 2 to 4, who
      averaged 22.7 min/d of predominantly light and moderate LTPA (range 10-36 min/d).
      No further decrement in mortality rates was noted in those in the higher declines
      of LTPA. These associations remained significant (P < 0.05) after proportional
      hazards adjustments for additional possible confounding variables. CONCLUSION:
      These data suggest that a relatively small amount (10 to 36 min/d) of daily
      moderate intensity LTPA can significantly reduce premature mortality,
      particularly from CHD, in middle-aged and older men at high risk for CHD.

PMID- 9272853
TI  - Describing the natural heterogeneity of aging using multilevel regression models.
AB  - Aging has been defined as the process of change that occurs in the individual
      during the course of time following the early stages of growth and development.
      While this process occurs in everyone, it varies from person to person.
      Longitudinal studies have emerged as the only method to study individual change
      directly and to identify factors associated with that change. Multilevel or mixed
      effects regression models have proven to be a useful tool for describing the
      natural heterogeneity that occurs in studies of aging. These models, along with
      recent developments in estimation procedures and numerical techniques, have made
      it possible to estimate in a unified analysis the average rates of change for the
      study population, as well as individual deviations from these average rates. One
      type of multilevel models, mixed-effects models, assumes that the correlation
      among longitudinal measurements for an individual is due to some latent
      characteristics that give the individual an initial level or rate of change which
      is higher or lower than average. This paper discusses the application of mixed
      effects models using random effects for the estimation of individual differences
      to aspects of human aging which have been observed over the first 35 years of the
      ongoing Baltimore Longitudinal Study of Aging.

PMID- 9272854
TI  - Time series analysis and its relationship with longitudinal analysis.
AB  - This paper discusses the relationship between longitudinal analysis of inter
      individual (co-)variation and time series analysis of intra-individual (co
      )variation. To set the stage for this discussion, first a tutorial overview of
      modern techniques of multivariate time series analysis is given which highlights
      the central role of rate-space modeling. Some increasingly general instances of
      the state-spuce model are presented, followed by a concise description of two
      recent applications involving nonlinear state-space modeling of oscillatory
      finger motion and nonlinear growth, respectively. We then consider the question
      under which conditions longitudinal factor analysis of inter-individual
      covariation will yield the same results as dynamic factor analysis of single
      subject time series data. The conditions concerned can be derived from ergodicity
      theory and turn out to be very restrictive. This implies that the results
      obtained in analyses of inter-individual variation (like the construction and
      validation of measurement scales) cannot be generalized to the assessment and
      prediction of individual developmental processes (e.g., in single-subject
      counseling). A simple illustration with simulated data is given, to the best of
      our knowledge for the first time, in which a factor analysis of inter-individual
      covariation yields a satisfactorily fitting solution that has no relationship
      whatsoever to the factor structures characterizing the intra-individual
      covariation of each subject in the sample.

PMID- 9272855
TI  - Problems and solutions in longitudinal research: from theory to practice.
AB  - Longitudinal studies provide the only method for directly studying the natural
      course of human growth and development and are therefore invaluable, both to
      public health and clinical medicine. However, longitudinal studies are
      accompanied by specific problems. The purpose of this final paper is to discuss
      in two separate sections some of the methodological, analytical and practical
      issues regarding the relevance of the findings reported. Examples of such
      problems and their solutions are described. Methodological issues discussed
      concern statistical conclusion validity, internal validity and construct validity
      of longitudinal studies. Practical issues discussed concern the design of
      longitudinal studies, the recruitment and retention of subjects, and the methods
      used. Finally, examples of the significance of longitudinal research outcomes to
      public health and clinical medicine are given.

PMID- 9272856
TI  - A rare type of overlapping genes in bacteriophage T4: gene 30.3' is completely
      embedded within gene 30.3 by one position downstream.
AB  - We have previously proposed the existence of one of the rarest types of
      overlapping genes in bacteriophage T4. We now present the results demonstrating
      that in a pair of T4 overlapping genes, 30.3 and 30.3', the smaller gene, 30.3',
      is entirely enclosed within the other by one position downstream. We have
      constructed plasmids in which different open reading frames from the gene 30.3
      region were fused with the 5' end of the lacZ beta-galactosidase (betaGal) gene
      of Escherichia coli. The gene fusions have been obtained at the position of a
      HindIII site which was introduced just upstream from the stop codon of gene
      30.3'. High betaGal activities have been estimated in the case of plasmids
      carrying 30.3::lacZ and 30.3'::lacZ fusions. The apparent molecular weights of
      the fusion proteins, the determined N-terminal sequences, as well as the detected
      betaGal activities, confirm the structure and arrangement of out-of-phase
      overlapping genes 30.3 and 30.3'.

PMID- 9272857
TI  - The sequence of palF, an environmental pH response gene in Aspergillus nidulans.
AB  - To molecularly characterize the influence of external pH in the secretion of
      enzymes by filamentous fungi, we have cloned and sequenced the palF gene of
      Aspergillus nidulans (An). An An wild-type (wt) chromosome VII-specific cosmid
      library was used to transform a palF15 mutant strain. Selection for
      complementation was done on medium containing beta-glycerolphosphate as the sole
      Pi source. Two cosmids were identified (W2G08 and W4G12) and further subcloning
      of one cosmid (W2G08) defined a 5-kb PstI genomic fragment, which fully
      complements the palF15 mutation. An internal fragment from the genomic clone
      recognized a single message of approx. 3.5 kb on Northern blot. cDNA clones were
      obtained from a lambda gt10 cDNA library and sequenced, showing a nucleotide (nt)
      sequence of 3311 base pairs (bp), with a 828 bp long 5'-untranslated region
      (UTR). The major open reading frame (ORF) identified in the sequence codes for a
      putative 775 amino acid (aa) protein, which shares some similarity with two
      putative ORF products of Saccharomyces cerevisiae (Sc).

PMID- 9272858
TI  - Complex gene organization of synaptic protein SNAP-25 in Drosophila melanogaster.
AB  - The evolutionarily conserved protein SNAP-25 (synaptosome-associated protein 25
      kDa (kilodaltons)) is a component of the protein complex involved in the docking
      and/or fusion of synaptic vesicles in nerve terminals. We report here that the
      SNAP-25 gene (Snap) in the fruit fly Drosophila melanogaster has a complex
      organization with eight exons spanning more than 120 kb (kilobases). The exon
      boundaries coincide with those of the chicken SNAP-25 gene (Bark, 1993). Only a
      single exon 5 has been found in Drosophila, whereas human, rat, chicken,
      zebrafish and goldfish have two alternatively spliced versions of this exon. In
      situ hybridization and immunocytochemistry to whole mount embryos show that SNAP
      25 mRNA and protein are detected in stage 14 and later developmental stages, and
      are mainly localized to the ventral nerve cord. Thus, Snap has an evolutionarily
      conserved and complex gene organization, and its onset of expression in
      Drosophila melanogaster correlates with a time in neuronal development when
      synapses begin to be formed and when other synapse-specific genes are switched
      on.

PMID- 9272859
TI  - Engineering Pichia pastoris for biocatalysis: co-production of two active
      enzymes.
AB  - High levels of active glycolate oxidase from spinach (GO) and active catalase T
      from Saccharomyces cerevisiae (catT) have been co-produced in the methylotrophic
      yeast Pichia pastoris (Pp). In sequential rounds of transformation using two
      selectable markers, multiple copies of the genes encoding GO and catT were
      integrated into the Pp chromosome under control of the methanol inducible alcohol
      oxidase I promoter, resulting in a strain designated MSP8.6. MSP8.6 is a second
      generation biocatalyst used for the conversion of glycolate to glyoxylate in the
      presence of a reaction component which inhibits endogenous Pp catalase. This work
      demonstrates a significant advance in the utility of recombinant Pp for
      commercial bioprocess development.

PMID- 9272860
TI  - Structure and expression of the gsa-1 gene encoding a G protein alpha(s) subunit
      in C. elegans.
AB  - The heterotrimeric guanine nucleotide-binding proteins (G proteins) act as
      switches in the signal transduction from cell surface receptors to a variety of
      effectors. Among them, Gs proteins stimulate adenylate cyclase activities and
      regulate ion channels in mammals. We identified the gsa-1 gene encoding a G
      protein alpha subunit in the nematode Caenorhabditis elegans. The predicted
      product consists of 375 amino acid residues, 66% of which are identical with
      those of a mammalian Gs(alpha) subunit. The gsa-1 gene was physically mapped near
      the left end of chromosome I. A gsa-1/lacZ fusion gene was expressed in many
      cells in embryos, larvae and adults, including neurons, body wall muscle cells
      and muscle cells of the pharynx and the vulva. The results presents a basis for
      genetic studies of the gsa-1 gene.

PMID- 9272861
TI  - Cloning and sequencing of a 35.7 kb in the 70 degree-73 degree region of the
      Bacillus subtilis genome reveal genes for a new two-component system, three spore
      germination proteins, an iron uptake system and a general stress response
      protein.
AB  - In the framework of the international project aimed at sequencing the Bacillus
      subtilis (Bs) genome, a 35.7-kb chromosome segment around the pel locus has been
      cloned and sequenced. This region (35,745 bp; 70 degrees-73 degrees of the
      genetic map) contains two partial and 38 complete orfs. A homology search for the
      products deduced from the 39 orfs revealed that 26 of them exhibit significant
      similarity to known proteins, e.g. germination proteins, sodium-alanine
      symporter, PTS system, methionine amino peptidase, 2-oxoglutarate/malate
      translocater, pectate lyase, general stress response protein, RNA helicase, iron
      uptake and two-component systems.

PMID- 9272862
TI  - Identification of factors regulating the expression of the human
      glucocerebrosidase gene.
AB  - Gaucher disease, the most prevalent sphingolipid disorder, is characterized by an
      accumulation of sphingolipids mainly in cells of the reticuloendothelial cells,
      and is due to decreased activity of the lysosomal enzyme glucocerebrosidase
      (GCase). The corresponding gene is expressed differentially, namely in different
      cell types there are different GCase steady-state mRNA levels. Electrophoretic
      mobility shift assays, DNase footprinting and chloramphenicol acetyl transferase
      assays were employed in order to unravel some of the transcription factors
      responsible for the differential expression of the glucocerebrosidase (gcs) gene.
      The results indicate that OCTA binding protein, AP-1, PEA3 and a CAAT binding
      protein participate in regulating the expression of the gcs gene. The
      availability of the transcription factors seems to control the level of
      transcription of the gcs gene.

PMID- 9272863
TI  - Three different genes encode NM23/nucleoside diphosphate kinases in Xenopus
      laevis.
AB  - Nucleoside diphosphate kinases (NDPKs) catalyse the phosphorylation of nucleoside
      diphosphates. In mammals, the functional enzyme is a hexamer composed of
      different amounts of two homologous acidic (A) and basic (B) subunits encoded by
      separate genes. In prokaryotes and invertebrate eukaryotes, only one cytoplasmic
      enzyme has been isolated. Other genes encoding chloroplastic and mitochondrial
      forms as well as related proteins have been cloned. Here, we show that in Xenopus
      laevis, as in mammals, the cytoplasmic NDPK is encoded by several homologous
      genes. With Xenopus laevis being a pseudotetraploid species, each monomer is
      encoded by two genes. The amino acid sequences are very similar, and all the
      differences concern amino acids located at the outer surface of the hexameric
      enzyme. The Xenopus genes share 82-87% identity with their human counterparts.
      Interestingly, in vitro, the Xenopus X1 enzyme binds to a specific nuclease
      hypersensitive element (NHE) of the human c-myc promoter, as does its human
      counterpart. X1 also binds to a single-stranded (CT)(n) dinucleotide repeat. The
      NHE is present in the coding strand of a pyrimidine-rich region of the 3' non
      coding sequence of the Xenopus NDPK genes. We propose that NDPK is indeed able to
      bind to its own mRNA and prevent polyadenylation at the normal position. This
      could provide an autoregulatory translation mechanism. A phylogenetic tree of the
      vertebrate NDPK sequences supports the idea that in amphibians, as in mammals,
      gene duplication has resulted in functional diversification.

PMID- 9272864
TI  - Integration of the yeast retrovirus-like element Ty3 upstream of a human tRNA
      gene expressed in yeast.
AB  - The retrovirus-like element Ty3 of Saccharomyces cerevisae integrates into the
      yeast genomic DNA in a position specific manner. Ty3 integrates within 1-2 base
      pairs of the site of transcription initiation by RNA polymerase III. The human
      tRNA(Lys)3 gene was used as a target for transposition in a plasmid-based assay
      to determine whether Ty3 integration can be targeted to a human tRNA gene. Each
      transposition event observed was adjacent to the site of initiation of
      transcription of the human tRNA gene. Therefore, heterologous tRNA genes can
      serve as targets for Ty3 in yeast. This is a first step toward development of a
      system for targeted integrations in heterologous organisms.

PMID- 9272865
TI  - Transcriptional regulation of a second flavodoxin gene from Klebsiella
      pneumoniae.
AB  - A second flavodoxin gene, distinct from the nifF gene encoding nitrogenase
      flavodoxin, has been isolated from Klebsiella pneumoniae. This flavodoxin gene is
      a homologue of the E. coli fldA gene and is located 286 bp upstream of the K.
      pneumoniae fur gene. Primer extension analysis revealed an unusual promoter
      region upstream of the K. pneumoniae fldA gene that does not match the -35/-10
      consensus sequence. Transcriptional analyses using a Fur titration assay and fldA
      gene fusions demonstrated that, unlike E. coli fldA, the K. pneumoniae fldA gene
      is not constitutively expressed. Rather, the fldA gene of K. pneumoniae is
      repressed in high iron conditions by the ferric uptake regulator (Fur) protein.
      Expression of K. pneumoniae fldA is also induced by heat shock but not by salt
      stress.

PMID- 9272866
TI  - Molecular cloning of a novel receptor-type protein tyrosine phosphatase from
      murine fetal liver.
AB  - A cDNA fragment encoding a novel tyrosine phosphatase (PTPase), termed ptpf, was
      isolated from day 11.5 mouse fetal liver using reverse transcription-polymerase
      chain reaction (RT-PCR) with degenerate primers. The 5.5-kb cDNA encoding the
      complete coding region was isolated from an adult mouse kidney cDNA library. This
      cDNA contained a single open reading frame (ORF) encoding a predicted 1436-amino
      acid protein with a molecular mass of 161,150 Da. Sequence analysis revealed that
      PTPf was homologous to PTPmu and PTPkappa, and a putative receptor-type PTPase.
      Northern blotting analysis of adult mouse mRNA indicated the existence of four
      major ptpf transcripts of approximately 10, 6, 3 and 2.7 kb, and these
      transcripts were expressed in a tissue-specific manner. During embryogenesis,
      only the 6-kb transcript was detected.

PMID- 9272867
TI  - Analysis of a Streptococcus pneumoniae gene encoding signal peptidase I and
      overproduction of the enzyme.
AB  - The spi gene of Streptococcus pneumoniae was cloned and its nucleotide sequence
      was determined. It encodes a protein of 204 amino acids that is homologous to
      bacterial signal peptidase I proteins. The S. pneumoniae protein contains all of
      the conserved amino acid sequence motifs previously identified in this enzyme
      from both prokaryotic and eukaryotic sources. Sequence comparisons revealed
      several additional motifs characteristic of the enzyme. The cloned S. pneumoniae
      gene complemented an Escherichia coli mutant defective in its leader peptidase
      gene. Expression of the spi gene in S. pneumoniae appeared to be essential for
      viability. The cloned gene was shown to produce a polypeptide of approximately 20
      kDa. Overproduction of the S. pneumoniae spi gene in an E. coli expression system
      gave a native protein product, soluble in the presence of a non-ionic detergent,
      which should be amenable to structural determination.

PMID- 9272868
TI  - Expression of individual members of a tRNA(Gly)1 multigene family in vivo follows
      the same pattern as in vitro.
AB  - Individual members of a tRNA(Gly)1 multigene family from Bombyx mori are
      transcribed to different levels in vitro in homologous nuclear extracts but their
      transcription status in vivo is not known. Two sets of tRNA(Gly)1 belonging to
      the extreme groups of highly transcribed and barely transcribed copies have been
      examined for their expression patterns in vivo in B. mori-derived cell lines
      following transfection. We have developed a sensitive and reliable method for
      directly quantifying the transcription levels of transfecting tRNA genes without
      relying on the biological activity of the transcript. The strategy involved the
      insertion of synthetic oligodeoxyribonucleotide sequences into the coding region
      of the transfecting gene and monitoring the transcripts in an RNase protection
      assay using an antisense probe that clearly distinguished them from the
      endogenous tRNAs. The oligonucleotide insertion did not significantly affect the
      transcriptional status of the genes, even though the distance between the A and B
      boxes was enhanced by 10-15 nt. In vivo also the transcription of tRNA(Gly)1
      reached very high levels, whereas the transcripts arising from tRNA(Gly)1-6:7
      accounted for only 2-5% of the former, closely resembling the transcription
      patterns in vitro. These individual gene copies having identical coding sequences
      and consequently the same internal conserved regions, differed only in their
      flanking sequences which modulate their transcription levels.

PMID- 9272869
TI  - Cloning and sequencing for the largest subunit of Chinese hamster RNA polymerase
      II gene: identification of a mutation related to abnormal induction of sister
      chromatid exchanges.
AB  - In order to analyze the mutation sites related to abnormal induction of sister
      chromatid exchanges (SCEs) in the RNA polymerase II largest subunit (RpII LS)
      gene of the Chinese hamster CHO-KI cell mutant, we have completely sequenced the
      whole region of the RpII LS cDNAs obtained from normal and mutant cells. By
      comparing both sequences, a mutation that results in an amino acid (aa) change in
      the RpII LS gene was found. This aa change was Pro (CCC) to Ser (TCC) at position
      1006. Multiple alignment for aa sequences of RpII LS from various species
      revealed that this Pro residue was highly conserved throughout the eukaryotes.
      Considering the differences in physico-chemical properties between Pro and Ser
      residues, the Pro-->Ser substitution may alter the RpII LS structure.

PMID- 9272870
TI  - Rapid amplification of genomic ends (RAGE) as a simple method to clone flanking
      genomic DNA.
AB  - This report describes the amplification of upstream genomic sequences using the
      polymerase chain reaction (PCR) based solely on downstream DNA information from a
      cDNA clone. In this novel and rapid technique, genomic DNA (gDNA) is first
      incubated with a restriction enzyme that recognizes a site within the 5' end of a
      gene, followed by denaturation and polyadenylation of its free 3' ends with
      terminal transferase. The modified gDNA is then used as template for PCR using a
      gene-specific primer complementary to a sequence in the 3' end of its cDNA and an
      anchored deoxyoligothymidine primer. A second round of PCR is then performed with
      a second, nested gene-specific primer and the anchor sequence primer. The
      resulting PCR product is cloned and its sequence determined. Three independent
      plant genomic clones were isolated using this method that exhibited complete
      sequence identity to their cDNAs and to the primers used in the amplification.

PMID- 9272871
TI  - Isolation of a mouse cDNA encoding mSTI1, a stress-inducible protein containing
      the TPR motif.
AB  - We report the isolation and sequencing of the complete 2079-bp cDNA fragment
      encoding mSTI1, a murine stress-inducible protein. The predicted ORF encodes a
      protein of 543 amino acids (aa) and Mr 62,582. The predicted protein has
      significant homology to stress-inducible proteins from humans (IEF SSP 3521),
      soybean (GMSTI), yeast (STI1) and a parasite, Leishmania donovani (LSIP). All of
      these proteins contain 34-aa repeat motifs, termed tetratricopeptide repeats
      (TPRs), that are proposed to be involved in intra- and intermolecular protein
      interactions. mSTI1 has ten potential TPR motifs, a putative nuclear localization
      signal (NLS), six potential phosphorylation sites for casein kinase II and a
      central proline-rich region. Western analysis detected a protein of approx. 63
      kDa in all the major mouse organs and in mouse, monkey and human cell lines.

PMID- 9272872
TI  - Cloning and characterization of the full length cDNA encoding alpha2 type I
      collagen of bullfrog Rana catesbeiana.
AB  - The present study determined nucleotide sequences of the full-length cDNA of
      alpha2 chain of bullfrog type I collagen. Hybridization of a bullfrog cDNA
      library with human alpha1 type I collagen cDNA yielded a clone named 6A-1 which
      was 3449 bp long and lacked a 5' region of the gene. A 5' region containing the
      translation initiation site was amplified by the reverse transcription polymerase
      chain reaction using poly(A)+RNA from tadpole tail tissues as template, and
      oligonucleotides encoding the translation initiation region of mammalian
      fibrillar collagens and the Gly-X-Y repeat region of clone 6A-1 as primers. As a
      result we obtained a 1518 bp long clone Y31. A 355 bp long clone Y31-9 was
      produced by extending clone Y31 from its ATG codon to a 127 bp upstream region.
      Combining these three clones, the complete nucleotide sequence of the full-length
      cDNA was determined which contained 4692 bp as a whole and 4065 bp in the open
      reading frame. The comparison of its structure with known collagen cDNAs of
      various vertebrates showed that the cDNA obtained codes for alpha2(I) chain of
      bullfrog. Its deduced amino acid sequence revealed the complete conservation of
      seven cysteine residues in the C-propeptide and three lysine residues in the N
      telopeptide through the helical domain. Northern blot analysis revealed that the
      thyroid hormone regulated the expression of alpha2(I) collagen in an organ
      dependent manner: intense up-regulation in the back skin and intestine, weak and
      transient up-regulation in the liver, and initial down-regulation, but later up
      regulation in the tail. Prolactin increased its expression in both the back skin
      and tail. These results suggested that the expression of bullfrog alpha2(I)
      collagen is cooperatively regulated by these two metamorphosis-regulating
      hormones.

PMID- 9272873
TI  - Identification of a new ribosomal RNA in Drosophila melanogaster.
AB  - This study reports the cloning, characterization and identification of a
      previously undetected ribosomal RNA in Drosophila melanogaster. The ribosomal RNA
      is 370 nucleotides in length and contains the 5.8S and 2S ribosomal RNA coding
      regions. Analysis of polysome-containing cell extracts indicates that the RNA is
      present on polysomes suggesting a functional role within the ribosome. Northern
      blot analysis indicates that the RNA is also present in adult Drosophila
      melanogaster flies.

PMID- 9272874
TI  - A novel gene encoding a ferredoxin reductase-like protein expressed in the
      neuroectoderm in Xenopus neurula.
AB  - In an attempt to elucidate the molecular mechanisms of early neural development
      in Xenopus laevis, we identified, using a differential display method, several
      genes that are induced after Concanavalin A treatment in the animal caps prepared
      from stage 9 blastula. One such gene was found to encode a possible type IIIa
      membrane protein of 66.2 kDa sharing similarities with several prokaryotic and
      eukaryotic redox enzymes, hence the putative product was named Nfrl, neurula
      specific ferredoxin reductase-like protein. Northern blot analysis confirmed that
      the expression of the Nfrl gene is up-regulated around the neurula stage, and is
      much lower in embryos of earlier stages and in adult tissues. The temporally
      limited expression of this gene implies neurula- and early larva-specific redox
      reactions of certain substrates, the nature of which remains to be elucidated.

PMID- 9272876
TI  - A piece of my mind. Seeking Aesculapius.

PMID- 9272875
TI  - Structure of the gene encoding human colligin-2 (CBP2).
AB  - Colligins are collagen-binding proteins localized to the endoplasmic reticulum
      that belong to the superfamily of serine protease inhibitors and play a role in
      collagen biosynthesis. Previously, we cloned the human colligin-2 gene (CBP2) and
      mapped it to chromosome 11q13.15. To further characterize the CBP2 gene, we have
      determined its genomic structure and the 5'-flanking sequence. The CBP2 gene
      spanned approximately 11 kb of genomic DNA and consisted of five exons. The
      promoter sequence of the human gene showed significant homology to that of its
      murine counterpart, which contained several regulatory sequences including heat
      shock and retinoic acid-responsive elements. These findings suggest colligin may
      function as a collagen-specific molecular chaperon and play a role in the process
      of retinoic acid-induced differentiation.

PMID- 9272878
TI  - FDA poster campaign targets teen smoking.

PMID- 9272877
TI  - Debating dual AIDS guidelines.

PMID- 9272879
TI  - Monoclonal antibody to treat lymphoma.

PMID- 9272880
TI  - Bioethics Commission examines informed consent from subjects who are
      'decisionally incapable'.

PMID- 9272881
TI  - From the Centers for Disease Control and Prevention. Landmine-related injuries,
      1993-1996.

PMID- 9272882
TI  - From the Centers for Disease Control and Prevention. Status report on the
      Childhood Immunization Initiative: national, state, and urban area vaccination
      coverage levels among children aged 19-35 months--United States, 1996.

PMID- 9272883
TI  - Patient consent for publication and the health of the public.

PMID- 9272884
TI  - Obtain informed consent before publishing information about patients.

PMID- 9272885
TI  - Meta-analysis of prevention of nonvertebral fractures by alendronate.

PMID- 9272886
TI  - Meta-analysis of prevention of nonvertebral fractures by alendronate.

PMID- 9272887
TI  - Quality of medical information on the Internet.

PMID- 9272888
TI  - Quality of medical information on the Internet.

PMID- 9272889
TI  - Evidence supporting cholesterol-lowering therapy for postmenopausal women with
      heart disease.

PMID- 9272890
TI  - The Papanicolaou test and screening for cervical cancer.

PMID- 9272891
TI  - Food poisoning following consumption of clenbuterol-treated veal in Italy.

PMID- 9272892
TI  - Expanding and understanding risk factors for coronary heart disease.

PMID- 9272893
TI  - Expanding and understanding risk factors for coronary heart disease.

PMID- 9272894
TI  - Expanding and understanding risk factors for coronary heart disease.

PMID- 9272895
TI  - Long-term effects of home visitation on maternal life course and child abuse and
      neglect. Fifteen-year follow-up of a randomized trial.
AB  - CONTEXT: Home-visitation services have been promoted as a means of improving
      maternal and child health and functioning. However, long-term effects have not
      been examined. OBJECTIVE: To examine the long-term effects of a program of
      prenatal and early childhood home visitation by nurses on women's life course and
      child abuse and neglect. DESIGN: Randomized trial. SETTING: Semirural community
      in New York. PARTICIPANTS: Of 400 consecutive pregnant women with no previous
      live births enrolled, 324 participated in a follow-up study when their children
      were 15 years old. INTERVENTION: Families received a mean of 9 home visits during
      pregnancy and 23 home visits from the child's birth through the second birthday.
      DATA SOURCES AND MEASURES: Women's use of welfare and number of subsequent
      children were based on self-report; their arrests and convictions were based on
      self-report and archived data from New York State. Verified reports of child
      abuse and neglect were abstracted from state records. MAIN RESULTS: During the 15
      year period after the birth of their first child, in contrast to women in the
      comparison group, women who were visited by nurses during pregnancy and infancy
      were identified as perpetrators of child abuse and neglect in 0.29 vs 0.54
      verified reports (P<.001). Among women who were unmarried and from households of
      low socioeconomic status at initial enrollment, in contrast to those in the
      comparison group, nurse-visited women had 1.3 vs 1.6 subsequent births (P=.02),
      65 vs 37 months between the birth of the first and a second child (P=.001), 60 vs
      90 months' receiving Aid to Families With Dependent Children (P=.005), 0.41 vs
      0.73 behavioral impairments due to use of alcohol and other drugs (P=.03), 0.18
      vs 0.58 arrests by self-report (P<.001), and 0.16 vs 0.90 arrests disclosed by
      New York State records (P<.001). CONCLUSIONS: This program of prenatal and early
      childhood home visitation by nurses can reduce the number of subsequent
      pregnancies, the use of welfare, child abuse and neglect, and criminal behavior
      on the part of low-income, unmarried mothers for up to 15 years after the birth
      of the first child.

PMID- 9272896
TI  - Effect of prenatal and infancy home visitation by nurses on pregnancy outcomes,
      childhood injuries, and repeated childbearing. A randomized controlled trial.
AB  - CONTEXT: Interest in home-visitation services as a way of improving maternal and
      child outcomes has grown out of the favorable results of a trial in semirural New
      York. The findings have not been replicated in other populations. OBJECTIVE: To
      test the effect of prenatal and infancy home visits by nurses on pregnancy
      induced hypertension, preterm delivery, and low birth weight; on children's
      injuries, immunizations, mental development, and behavioral problems; and on
      maternal life course. DESIGN: Randomized controlled trial. SETTING: Public system
      of obstetric care in Memphis, Tenn. PARTICIPANTS: A total of 1139 primarily
      African-American women at less than 29 weeks' gestation, with no previous live
      births, and with at least 2 sociodemographic risk characteristics (unmarried, <12
      years of education, unemployed). INTERVENTION: Nurses made an average of 7
      (range, 0-18) home visits during pregnancy and 26 (range, 0-71) visits from birth
      to the children's second birthdays. MAIN OUTCOME MEASURES: Pregnancy-induced
      hypertension, preterm delivery, low birth weight, children's injuries,
      ingestions, and immunizations abstracted from medical records; mothers' reports
      of children's behavioral problems; tests of children's mental development;
      mothers' reports of subsequent pregnancy, educational achievement, and labor
      force participation; and use of welfare derived from state records. MAIN RESULTS:
      In contrast to counterparts assigned to the comparison condition, fewer women
      visited by nurses during pregnancy had pregnancy-induced hypertension (13% vs
      20%; P=.009). During the first 2 years after delivery, women visited by nurses
      during pregnancy and the first 2 years of the child's life had fewer health care
      encounters for children in which injuries or ingestions were detected (0.43 vs
      0.55; P=.05); days that children were hospitalized with injuries or ingestions
      (0.03 vs 0.16; P<.001); and second pregnancies (36% vs 47%; P=.006). There were
      no program effects on preterm delivery or low birth weight; children's
      immunization rates, mental development, or behavioral problems; or mothers'
      education and employment. CONCLUSION: This program of home visitation by nurses
      can reduce pregnancy-induced hypertension, childhood injuries, and subsequent
      pregnancies among low-income women with no previous live births.

PMID- 9272897
TI  - The impact of Mississippi's mandatory delay law on abortions and births.
AB  - CONTEXT: Beginning August 8, 1992, a woman in the state of Mississippi had to
      wait 24 hours after in-person receipt of state-mandated information regarding
      abortion and birth complications, fetal development, and alternatives to abortion
      before an abortion could be performed. OBJECTIVE: To analyze the effect of the
      law on the abortion and birth rates of Mississippi residents. DESIGN: A
      retrospective analysis of abortion and birth rates before and after the law in
      Mississippi as contrasted with abortion and birth rates in 2 comparison states,
      Georgia and South Carolina. Neither Georgia nor South Carolina enforced a
      mandatory delay law, but both states began enforcement of parental notification
      statutes during the study period. PATIENTS: Female residents of reproductive age
      in Mississippi, Georgia, and South Carolina between 1989 and 1994. MAIN OUTCOME
      MEASURES: We compared birth rates, abortion rates, the percentage of late
      abortions, and the percentage of abortions performed outside the state of
      residence for all women and then by age and race before and after August 1992
      among women of Mississippi, Georgia, and South Carolina. RESULTS: We found that
      rate ratios (RRs) of resident abortion rates (rate after law implementation/rate
      before law implementation) declined 12% more in Mississippi than in South
      Carolina (95% confidence interval [CI], 8%-15%) and 14% more in Mississippi than
      in Georgia (95% CI, 10%-17%) in the 12 months after the law went into effect.
      Rate ratios for white adults declined 22% more in Mississippi than in South
      Carolina (95% CI, 17%-27%) and 20% more in Mississippi than in Georgia (95% CI,
      15%-25%). Changes among nonwhite adults and white teens were more modest but also
      statistically significant (P<.05). For all women, RRs of the percentage of
      abortions performed after 12 weeks' gestation increased 39% more in Mississippi
      than in either South Carolina or Georgia (P<.05); the increase in the percentage
      of abortions after 12 weeks' gestation was observed for white and non-white
      adults (P<.05). We also show that the percentage of abortions performed out of
      state increased 42% more among women in Mississippi relative to women in South
      Carolina after the law (95% CI, 34%-50%). CONCLUSION: The timing of the decline
      in abortion rates in Mississippi, the lack of similar declines in comparison
      states, the rise in percentage of late abortions and abortions performed out of
      state and the apparent completeness of abortion reports suggest that
      Mississippi's mandatory delay statute was responsible for a decline in abortion
      rates and an increase in abortions performed later in pregnancy among residents
      of Mississippi. The effect of delay laws in other states will likely depend on
      whether statutes require 2 separate visits to the abortion provider (ie, clinics,
      hospitals, or physicians' offices where abortions are performed) and the
      availability of abortion services.

PMID- 9272898
TI  - Gastric acidity in older adults.
AB  - CONTEXT: Early studies suggested that gastric acidity declines as people age.
      However, sequelae of achlorhydria are uncommon in older people, making this
      conventional wisdom unlikely. OBJECTIVE: To ascertain the prevalence of basal
      gastric acidity and atrophic gastritis (indicated by serum pepsinogen ratio) in
      older adults. DESIGN: Cross-sectional study in a volunteer sample. SETTING:
      Retirement communities in suburbs of Kansas City, Mo. SUBJECTS: A total of 248
      white male and female volunteers aged 65 years or older living independently.
      MAIN OUTCOME MEASURES: Presence of basal unstimulated gastric acid was evaluated
      noninvasively by having subjects swallow quininium resin. Gastric acid with a pH
      lower than 3.5 releases quinine, which is then absorbed and excreted into urine.
      Atrophic gastritis was defined as a ratio of serum pepsinogen I/pepsinogen II of
      less than 2.9. RESULTS: Basal unstimulated gastric content was acidic (pH <3.5)
      in 208 (84%) of 248 elderly subjects. On retesting 66 subjects (35 normals and 31
      hyposecretors), 28 (80%) of 35 had pH less than 3.5 both times, and 22 (71%) of
      31 had pH of 3.5 or higher twice; in the remaining 16 subjects, low vs high
      gastric pH changed between tests. Weighted population prevalence estimates in
      this sample were 67% for consistent acid secretion, 22% for intermittent
      secretion, and 11% for consistent gastric pH higher than 3.5. Whereas 14 (67%) of
      21 consistent hyposecretors had serum pepsinogen ratios of less than 2.9,
      indicating atrophic gastritis, only 2 (5%) of 44 consistent or intermittent
      secretors of acid had ratios in this range (P<.001). CONCLUSIONS: In contrast to
      what is commonly stated, nearly 90% of elderly people in this study were able to
      acidify gastric contents, even in the basal, unstimulated state. Of those who
      were consistent hyposecretors of acid, most had serum markers of atrophic
      gastritis.

PMID- 9272899
TI  - Personal watercraft-related injuries. A growing public health concern.
AB  - CONTEXT: An increase in the recreational use of personal watercraft (PWC) raises
      concern about an increase in associated injuries on a national level. OBJECTIVE:
      To estimate the relative frequency, types of injury, and demographic features of
      persons injured while using PWC in the United States. DESIGN: Case series.
      SETTING: Emergency department (ED) visits to hospitals participating a national
      probability sample. PARTICIPANTS: All persons treated for PWC-related injury from
      January 1,1990, through December 31, 1995. RESULTS: An estimated 32954 persons
      (95% confidence interval [CI], 22919-42989) with PWC-related injuries were
      treated in US hospital EDs, of which 3.5% were hospitalized. Personal watercraft
      related injuries have increased significantly from an estimated 2860 in 1990 to
      more than 12000 in 1995. During this period, the number of PWC in operation
      increased 3-fold from approximately 241500 in 1990 to an estimated 760000 in
      1995. The most prevalent diagnoses were lacerations, contusions, and fractures.
      MAIN OUTCOME MEASURES: The estimated number and percentage of patients treated in
      EDs for PWC-related injuries, by year, age, sex, and the number and rate per 1000
      of PWC in operation by year. CONCLUSIONS: Since 1990, there has been at least a 4
      fold increase in injuries associated with an increase in the recreational use of
      PWC. The rate of ED-treated injuries related to PWC was about 8.5 times higher
      (95% CI, 8.2-8.8; 1992 data) than the rate of those from motorboats. Specific
      training and adult supervision is recommended for minors using PWC. Furthermore,
      medical practitioners should encourage personal flotation device use and other
      protection for their patients who are known water enthusiasts.

PMID- 9272901
TI  - A 37-year-old man with multiple somatic complaints.

PMID- 9272900
TI  - Brain serotonin neurotoxicity and primary pulmonary hypertension from
      fenfluramine and dexfenfluramine. A systematic review of the evidence.
AB  - OBJECTIVES: Obesity is an important clinical problem, and the use of
      dexfenfluramine hydrochloride for weight reduction has been widely publicized
      since its approval by the Food and Drug Administration. However, animal and human
      studies have demonstrated toxic effects of fenfluramines that clinicians should
      be aware of when considering prescribing the drugs. Our purpose was to
      systematically review data on brain serotonin neurotoxicity in animals treated
      with fenfluramines and the evidence linking fenfluramines to primary pulmonary
      hypertension (PPH). DATA SOURCES: Archival articles and reviews identified
      through a computerized search of MEDLINE from 1966 to April 1997 using
      "fenfluramine(s)," "serotonin," "neurotoxicity," "behavior," "anorexigens,"
      "weight loss," and "primary pulmonary hypertension" as index terms. STUDY
      SELECTION: Reports dealing with long-term effects of fenfluramines on brain
      serotonin neurons, body weight, and pulmonary function in animals and humans.
      DATA EXTRACTION: Reports were reviewed by individuals with expertise in serotonin
      neurobiology, neurotoxicity, neuropsychiatry, and pulmonary medicine and
      evaluated for appropriateness for inclusion in this review. DATA SYNTHESIS:
      Fenfluramines cause dose-related, long-lasting reductions in serotonin axonal
      markers in all the animal species tested and with all the routes of drug
      administration used. Doses of fenfluramines that produce signs of brain serotonin
      neurotoxicity in animals are on the same order as those used to treat humans for
      weight loss when one takes into account known relations between body mass and
      drug clearance. However, no human studies have been conducted, and the
      pathological and clinical potential for neurotoxicity in humans is unknown.
      Appetite suppressants-most commonly fenfluramines-increase the risk of developing
      PPH (odds ratio, 6.3), particularly when used for more than 3 months (odds ratio,
      >20). CONCLUSIONS: Fenfluramine and dexfenfluramine have been demonstrated to
      damage brain serotonin neurons in animal studies. It is not known if such damage
      occurs in humans or if there are clinical consequences. Use of fenfluramines is
      associated with an increased risk of PPH. Future studies should address the long
      term consequences of prolonged use of fenfluramines.

PMID- 9272902
TI  - An 89-year-old woman with urinary incontinence, 1 year later.

PMID- 9272903
TI  - Helping poor mothers and children.

PMID- 9272904
TI  - The mature stomach. Still pumping out acid?

PMID- 9272905
TI  - Informed consent for publication.

PMID- 9272906
TI  - Full polysomnography versus home sleep study: searching for the optimal
      procedure.

PMID- 9272907
TI  - Malignant pleural effusion: would the real cause please stand up?

PMID- 9272908
TI  - Pulmonary perspective: immunology in diagnosis and treatment of lung cancer.
AB  - The combination of the limits encountered with current therapies and the
      increased knowledge of immunology have opened perspectives for the use of
      immunomodulators in the management of lung cancer patients. Both humoral and
      cellular immunity are now evaluated in diagnosis and treatment of cancer.
      Monoclonal antibodies (MoAbs) against tumour-associated antigens are now tested
      with various imaging techniques to improve detection and staging of lung cancer.
      MoAbs are also used in therapeutic clinical trials as: 1) mediators of immune
      effector function; 2) carriers of cytotoxic agents; 3) agents to block tumour
      growth factor; or 4) anti-idiotype vaccines. Immune effector cells, such as
      natural killer (NK) cells, T- and B-lymphocytes, macrophages, dendritic cells and
      neutrophils, are present either within or around tumours and are likely to play a
      role in cancer. These cells, either alone or with cytokines, could provide new
      efficient therapeutic approaches, particularly if immunosuppression is involved
      in tumour progression. In this context, most recent studies using immune cells
      and molecular bioengineering, could provide additional antitumoral effects.
      Finally, the discovery of several tumour rejection antigens has revived the dream
      of designing tumour vaccines and active specific immunotherapy.

PMID- 9272909
TI  - Should patients with sleep apnoea/hypopnoea syndrome be diagnosed and managed on
      the basis of home sleep studies?
AB  - The purpose of this study was to analyse the validity and the economic efficiency
      of a portable monitor of respiratory parameters (PMRP), used in a home setting
      for the diagnosis of sleep apnoea/hypopnoea syndrome (SAHS). Eighty nine patients
      with suspected SAHS were studied in two settings: in the sleep laboratory using
      full-polysomnography (full-PSG); and at the patient's home using a PMRP. In the
      home setting, 50 patients were assisted by a technician and 39 set up the
      equipment themselves. SAHS (apnoea/hypopnoea index (AHI) >10 events x h(-1) by
      means of full-PSG) was diagnosed in 75 of the 89 patients. An acceptable
      agreement was obtained between the AHI measured by full-PSG and PMRP, according
      to the Bland and Altman method of concordance (mean bias 2.56; 95% confidence
      interval 3.25). Sensitivity and specificity of PMRP were adequate for diagnostic
      purposes; however, their values rely on the prior PMRP-AHI cut-off point selected
      with reference to full-PSG-AHI >10. The clinical therapeutic decision taken after
      PMRP agreed with that taken with full-PSG in 79 patients (89%). Although 10% of
      the studies with an individual set-up needed repetition, both of the domiciliary
      modalities (with and without a technician's intervention) were, economically,
      about three times more efficient than full-PSG. In conclusion, we believe that
      patients with a suspected sleep apnoea/hypopnoea syndrome should initially be
      studied in a home setting with a portable monitor of respiratory parameters,
      since it is a reliable method with an acceptable cost-effective profile.

PMID- 9272910
TI  - Obstructive sleep apnoea syndrome: is the "half-night polysomnography" an
      adequate method for evaluating sleep profile and respiratory events?
AB  - Recently, to reduce the costs of polysomnography, split-night studies have been
      introduced into routine practice: the first part of the night is used to make the
      diagnosis of obstructive sleep apnoea syndrome (OSAS) and the second part to
      achieve an appropriate level of continuous positive airway pressure. Since this
      split-night protocol has not yet been validated by the comparison of
      polysomnographic pictures obtained in the first and second parts of the night,
      the aim of this study was to evaluate sleep profile and respiratory disturbances
      in the first part (PSG1) and second (PSG2) portion of a standard full-night
      polysomnographic examination (PSGtot) in a group of OSAS patients. Twenty nine
      consecutive OSAS patients, aged 54+/-10 yrs; body mass index (BMI) 40+/-6 kg x m(
      2) (mean+/-SD values), were studied by separate analyses of PSG1, PSG2 and
      PSGtot. PSG1 was found to have a low sensitivity value (66%). A significant
      difference was found between apnoea-hypopnoea indices (AHI) recorded in PSG1,
      PSG2 and PSGtot (mean+/-SD, AHI1 33+/-27, AHI2 45+/-28, AHItot 40+/-25 events x
      h(-1), respectively; p<0.01). A strong correlation was observed between AHItot
      and AHI1 (r=0.89) and between AHItot and AHI2 (r=0.92), but a weaker correlation
      between AHI1 and AHI2 (r=0.66). These correlations became weaker when patients
      were subdivided into two different classes on the basis of disease severity. PSG1
      was representative of PSGtot and similar to PSG2 only in those patients with
      rapid eye movement (REM) phase sleep in the first part of the night. We conclude
      that split-night protocols are not appropriate for evaluating sleep-disordered
      breathing in obstructive sleep apnoea syndrome patients when rapid eye movement
      phase sleep does not occur in the first part of the night.

PMID- 9272911
TI  - Sleep-related O2 desaturation and daytime pulmonary haemodynamics in COPD
      patients with mild hypoxaemia.
AB  - It has been hypothesized but not firmly established that sleep-related hypoxaemia
      could favour the development of pulmonary hypertension in chronic obstructive
      pulmonary disease (COPD) patients without marked daytime hypoxaemia. We have
      investigated the relationships between pulmonary function data, sleep-related
      desaturation and daytime pulmonary haemodynamics in a group of 94 COPD patients
      not qualifying for conventional O2 therapy (daytime arterial oxygen tension
      (Pa,O2) in the range 7.4-9.2 kPa (56-69 mmHg)). Nocturnal desaturation was
      defined by spending > or = 30% of the recording time with a transcutaneous O2
      saturation < 90%. An obstructive sleep apnoea syndrome was excluded by
      polysomnography. Sixty six patients were desaturators (Group 1) and 28 were
      nondesaturators (Group 2). There was no significant difference between Groups 1
      and 2 with regard to pulmonary volumes and Pa,O2 (8.4+/-0.6 vs 8.4+/-0.4 kPa
      (63+/-4 vs 63+/-3 mmHg)) but arterial carbon dioxide tension (Pa,CO2) was higher
      in Group 1 (6.0+/-0.7 vs 53+/-0.5 kPa (45+/-5 vs 40+/-4 mmHg); p<0.0001). Mean
      pulmonary artery pressure (Ppa) was very similar in the two groups (2.6+/-0.7 vs
      2.5+/-0.6 kPa (19+/-5 vs 19+/-4 mmHg)). No individual variable or combination of
      variables could predict the presence of pulmonary hypertension. It is concluded
      that in these patients with chronic obstructive pulmonary disease with modest
      daytime hypoxaemia, functional and gasometric variables (with the noticeable
      exception of arterial carbon dioxide tension) cannot predict the presence of
      nocturnal desaturation; and that mean pulmonary artery pressure is not correlated
      with the degree and duration of nocturnal hypoxaemia. These results do not
      support the hypothesis that sleep-related hypoxaemia favours the development of
      pulmonary hypertension.

PMID- 9272913
TI  - Inflammatory cells and activation markers in BAL during acute rejection and
      infection in lung transplant recipients: a prospective, longitudinal study.
AB  - Acute rejection of the transplanted lung is a clinical problem, since it
      decreases graft survival and predisposes the patient to chronic rejection and
      obliterative bronchiolitis (OB). In an earlier study, we had indications that
      eosinophil cationic protein (ECP) from activated eosinophils and hyaluronan (HYA)
      from fibroblasts were associated with acute pulmonary rejection. This prospective
      longitudinal study was designed to investigate whether molecules from activated
      inflammatory cells in bronchoalveolar lavage (BAL) fluid could serve as
      clinically useful diagnostic markers for acute rejection. BAL fluid from 138
      bronchoscopies performed in 10 single lung, four bilateral lung and five heart
      lung transplant recipients were analysed. Nine patients were studied for a period
      of more than 1 yr (mean 13.4 months) after surgery. Differential cell counts were
      made from the BAL fluid. ECP, myeloperoxidase (MPO), HYA and interleukin-8 (IL-8)
      were used as indirect markers for activation and attraction of eosinophils,
      neutrophils and fibroblasts, respectively. Fifty four episodes of acute rejection
      were diagnosed. Two patients developed OB. Nine episodes of bacterial infection,
      13 episodes of cytomegalovirus (CMV) pneumonitis, three of Pneumocystis carinii
      infection and one of respiratory syncytial virus (RSV) infection were diagnosed.
      The mean levels of ECP, MPO, HYA and IL-8 were all higher during rejection
      episodes, but differences were not statistically significant compared to no
      rejection, when the confounding factors of time, concomitant infection, and
      repeated measures in the same individual had been accounted for. We could not
      confirm that measurements of eosinophil cationic protein, myeloperoxidase,
      hyaluronan and interleukin-8 in bronchoalveolar lavage fluid can be used as
      diagnostic markers for acute rejection in the postoperative follow-up of lung
      transplant recipients.

PMID- 9272912
TI  - Expression of complement receptors and regulatory proteins on alveolar CD4+
      lymphocytes from human immunodeficiency virus-1 infected individuals.
AB  - Several lines of evidence suggest a dysregulation of the complement system in
      human immunodeficiency virus-1 (HIV-1) infected patients. The aim of this study
      was to elucidate whether CD4+ alveolar lymphocytes from HIV-1 infected patients
      show a loss of complement regulatory proteins that would render these cells
      susceptible to antibody-dependent complement-mediated cytotoxicity. We
      investigated the expression of complement regulatory (CD46, CD55, CD59) and
      complement receptor (CR1, CR2, CR3, CR4) proteins on alveolar cells by flow
      cytometry. Cells were obtained by bronchoalveolar lavage from 17 HIV-1 infected
      and 12 HIV-1 negative individuals. Expression of adhesion molecules (leucocyte
      functional associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM
      1)) and CD30 were evaluated in patient subgroups. In addition, interleukin (IL)
      1beta, tumour necrosis factor alpha (TNF-alpha), IL-4 and interferon gamma (IFN
      gamma) concentrations were measured in supernatants of alveolar cells. We found a
      significantly reduced expression of CD46 and CD59 on CD4+ alveolar lymphocytes
      from HIV-1 infected individuals, whereas the expression of CR3, CR4, ICAM-1 and
      CD30 was increased. IL-1beta and TNF-alpha concentration in supernatants of
      alveolar cells was augmented in HIV-1 infected patients, but did not correlate
      with the expression of surface molecules. IFN-gamma concentration was also
      increased and showed an inverse relationship to the surface expression of CD30 on
      CD4+. Our data suggest that in human immunodeficiency virus-1 infection an
      increased level of activation is associated with a diminished expression of
      complement regulatory proteins on CD4+ alveolar lymphocytes. This phenomenon
      might contribute to the depletion of CD4+ lymphocytes and the local
      immunodeficiency in the pulmonary compartment.

PMID- 9272914
TI  - Kinin generation in acute pneumonia and chronic bronchitis.
AB  - Kinins are potent inflammatory mediators, liberated from kininogens by different
      kininogenases. The aim of this study was to investigate the kinin generation
      pathways in acute and chronic inflammation of the lower airways. We studied
      bronchoalveolar lavage fluid (BALF) of patients with acute pneumonia, patients
      with chronic bronchitis and healthy controls. Kinins were determined by
      radioimmunoassay (RIA). Plasma kallikrein (pl-Kal), alpha2-macroglobulin (alpha2
      M) and toluenesulphonylarginine methyl ester (TAME) esterase activity (TAME-ea)
      were studied in BALF before and after gel filtration chromatography. Plasma
      kallikrein and alpha2-M were measured using two newly developed sandwich enzyme
      linked immunosorbent assays (ELISAs). TAME-ea was measured by a radiochemical
      assay. After gel filtration, inhibition of TAME-ea with benzamidine, soy-bean
      trypsin inhibitor (SBTI) and aprotinin was performed. Kinins and TAME-ea did not
      differ significantly between acute pneumonia and chronic bronchitis, whereas pl
      Kal and alpha2-M values were significantly higher in acute pneumonia. Gel
      filtration revealed the highest TAME-ea peak in acute pneumonia corresponding
      with the first alpha2-M peak at approximately 800 kDa, whereas in chronic
      bronchitis the highest peak was found at approximately 40 kDa. The inhibition
      test showed that the TAME-ea peak at approximately 800 kDa was due to pl-Kal and
      the TAME-ea peak at approximately 40 kDa was mainly due to tissue kallikrein.
      High peaks of alpha2-M and pl-Kal were found in pneumonia and only small peaks
      were seen in chronic bronchitis. We conclude that in acute airway inflammation
      kinins seem to be mainly generated by plasma kallikrein whereas in chronic
      inflammation, kininogenases other than plasma kallikrein, such as tissue
      kallikrein, seem to be more important.

PMID- 9272915
TI  - Effect of sputum bacteriology on the quality of life of patients with
      bronchiectasis.
AB  - Bronchiectatic patients have impaired health-related quality of life (QoL) and
      are prone to chronic lower respiratory tract infections. We have investigated
      whether impaired QoL is related to sputum bacteriology. Eighty seven patients
      with non-cystic fibrosis (non-CF) bronchiectasis, in a stable phase of their
      illness, completed three QoL measures, underwent a computed tomography (CT) scan
      and lung function tests, and provided a fresh sputum sample for microscopy and
      culture. The QoL of patients colonized by Pseudomonas aeruginosa (Pa group) was
      significantly worse than all other patients grouped together (non-Pa group), and
      specifically those infected by Haemophilus influenzae (Hi group) or who had no
      bacterial growth (NG group) (p<0.05), but not those infected by other bacterial
      species (O group). The Pa group had worse lung function, but no significant
      differences were found between the groups for forced expiratory volume in one
      second (FEV1) and peak expiratory flow rate. The Pa group had significantly worse
      bronchiectasis scores than the O, NG and non-Pa groups, but not the Hi group.
      There were no significant differences between the groups with respect to the
      number of infective exacerbations in the last year, but the Pa group had
      significantly more hospital admissions. Patients infected by P. aeruginosa for
      more than 3 yrs had significantly worse FEV1 (p<0.03) and bronchiectasis scores
      (p<0.05) than those infected with P. aeruginosa for less time, but not
      significantly worse QoL. We conclude that, overall, patients infected with P.
      aeruginosa have worse quality of life, and that P. aeruginosa is associated with
      a greater extent of disease and worse lung function. Although patients infected
      with H. influenzae had extensive bronchiectasis their quality of life was better
      than the P. aeruginosa infected group.

PMID- 9272916
TI  - Use of the paediatric bronchoscope, flexible and rigid, in 51 European centres.
AB  - We have undertaken a survey to establish current practices and differences in the
      use of bronchoscopes in children in European centres. A questionnaire was sent to
      all 220 members of the Paediatric Assembly of the European Respiratory Society
      (ERS). The questions concerned the following points: indications for
      bronchoscopy; site of bronchoscopy; type of sedation; any oxygen supplementation
      during the procedure; number of procedures performed in the previous 12 months;
      number of procedures performed in the neonatal intensive care unit; number of
      bronchoalveolar lavages (BALs); side-effects during and after the procedures; and
      diagnostic yield. Fifty one European centres (40.8% of the European centres
      contacted) took part in the study. A total of 7,446 bronchoscopies had been
      performed in the last 12 months: 4,587 using the flexible bronchoscope and 2,859
      using the rigid bronchoscope. At centres using only the fibreoptic bronchoscope,
      the most frequent indication was "recurrent/persistent pneumonia" (17%); at
      centres using only the rigid bronchoscope, it was "foreign body inhalation"
      (36.7%); at centres using both methods, the most frequent indication was "other
      indications" (23.9%). In 12 months, 2,231 BALs were performed: 1,419 in
      immunocompetent children and 812 in immunocompromised patients. In centres using
      only the fibreoptic bronchoscope, the highest yield was for "stridor" (81%); in
      centres using only the rigid bronchoscope, the highest yield was for "persistent
      atelectasis" (68%); and in centres using both instruments, it was for "foreign
      body inhalation" (93%). The results of the study suggest that bronchoscopy in
      children is now a well-established procedure at several European centres, while
      others are just beginning to use this technique.

PMID- 9272917
TI  - Increased spontaneous release of tumour necrosis factor-alpha by alveolar
      macrophages from wheezy infants.
AB  - We determined if alveolar macrophages (AMs) from infants with severe recurrent
      wheezing episodes release increased amounts of tumour necrosis factor-alpha (TNF
      alpha), as described in adults with asthma. We compared TNF-alpha release by
      unstimulated and lipopolysaccharide-stimulated AMs obtained by bronchoalveolar
      lavage in 13 wheezy and seven nonwheezy infants (aged 6-36 months) and analysed
      its regulation by dexamethasone. Metabolites in cell supernatants were quantified
      by enzyme-linked immunosorbent assay (ELISA) (TNF-alpha) or radioimmunoassay
      (thromboxane B2 and prostaglandin E2). Comparison of results was performed by the
      Mann-Whitney U-test and values were expressed as median (interquartile range) in
      ng x 10(6) cells(-1). Resting AMs from wheezy infants released larger amounts of
      TNF-alpha and thromboxane B2 as compared to controls: 2.67 (0.89-8.33) vs 0.48
      (0.25-1.08) and 75.63 (38.07-158.91) vs 10.03 (7.36-76.08), respectively
      (p<0.05). When stimulated overnight with bacterial lipopolysaccharide, AMs from
      both groups released similar amounts of metabolites. Dexamethasone induced a
      consistent inhibition of the lipopolysaccharide-stimulated release of all the
      mediators. Our results show that alveolar macrophages from wheezy infants are
      activated to release increased amounts of tumour necrosis factor-alpha, as in
      asthma, and suggest that infants with recurrent wheezing may eventually benefit
      from treatment with glucocorticoids.

PMID- 9272918
TI  - In utero exposure to cigarette smoking influences lung function at birth.
AB  - To avoid the possible confounding effects of postnatal exposure to tobacco smoke,
      we investigated possible effects of uterine tobacco smoke (UTS) exposure upon
      infant lung function shortly after birth. Infants with no major disease, in one
      maternity ward in Oslo, Norway, participating in a cohort study established in
      1992/1993, were included in the present study (n=803). Exposure information,
      assessed as maternal active and passive smoking during pregnancy and other
      personal and environmental factors, was obtained by questionnaire. Tidal flow
      volume (TFV) loops (n=802) and compliance (Crs) and resistance (Rrs) of the
      respiratory system (n=663) were measured at a mean age of 2.7 days. In girls, the
      TFV ratio (time to reach peak expiratory flow to total expiratory time
      (tPEF/tE)), and Crs were significantly lower with active as well as passive
      maternal smoking compared to nonexposure to UTS. Respiratory rate and Rrs were
      not significantly influenced by UTS exposure. However, in linear regression
      analysis adjusted for confounding factors (including respiratory rate), tPEF/tE
      and Crs, but not Rrs, were related to maternal active but not passive daily
      smoking. One daily cigarette corresponded to a change in tPEF/tE of -0.0021 (95%
      confidence interval (95% CI) -0.0040 to -0.0002) and a change in Crs of -0.026 mL
      x cmH2O (95% CI -0.045 to -0.007 mL x cmH2O). The decrease was 0.023 and 0.29,
      respectively, in infants of an average smoker. Maternal smoking during pregnancy
      adversely affected tidal flow-volume ratios in healthy newborn babies, as well as
      the compliance of the respiratory system in girls, independently of the reduced
      body size also resulting from maternal smoking.

PMID- 9272919
TI  - Asthma and respiratory symptoms in 6-7 yr old Italian children: gender, latitude,
      urbanization and socioeconomic factors. SIDRIA (Italian Studies on Respiratory
      Disorders in Childhood and the Environment).
AB  - Little information is available on the epidemiology of childhood respiratory
      disorders in Southern Europe. We investigated the prevalence of asthma and
      respiratory symptoms in a large sample of schoolchildren, according to gender,
      latitude, urbanization, and socioeconomic status. Questionnaires including the
      International Study of Asthma and Allergies in Childhood (ISAAC) core module on
      wheeze, as well as questions about other respiratory symptoms (including cough
      and phlegm), were completed by the parents of 18,737 schoolchildren aged 6-7 yrs,
      from eight centres of northern and central Italy. Wheeze in the last 12 months
      was reported for 9% of males and 6% of females, and severe wheezing attacks for
      1.4 and 0.8%, respectively. Asthma during lifetime was reported for 11% of males
      and 6.4% of females. The prevalence of physician-diagnosed asthma increased with
      level of urbanization, but reported wheezing did not, suggesting a labelling
      bias. Socioeconomic status was not associated with the prevalence of most
      wheezing symptoms or of physician-diagnosed asthma, but was negatively correlated
      with the number of hospital admissions because of asthma. Unlike wheezing
      symptoms, the prevalence of chronic cough and phlegm was associated with
      increasing urbanization and decreasing socioeconomic level. Urbanization and
      socioeconomic level have little effect on the prevalence of wheezing in this
      area, but they might influence the diagnosis and the management of asthma, as
      well as the prevalence of chronic cough and chronic phlegm.

PMID- 9272920
TI  - Prevalence of asthma symptoms in video and written questionnaires among children
      in four regions of Finland.
AB  - The aim of this study was to determine whether there are regional differences in
      the prevalence of childhood asthma in Finland. A secondary objective was to
      assess the concordance between a written and a video questionnaire on asthma
      symptoms. In 1994-1995, the self-reported prevalence of asthma symptoms in four
      regions of Finland was studied among 11,607 schoolchildren aged 13-14 yrs, as
      part of the International Study of Asthma and Allergies in Childhood (ISAAC). The
      ISAAC written and video (AVQ 3,0) questionnaires were administered in the school
      setting. The prevalences of any wheezing during the previous 12 months in the
      ISAAC video questionnaire were 10% in East Finland (Kuopio County, n=2,821), 12%
      in South Finland (Helsinki area, n=2,771), 12% in Southwest Finland (Turku and
      Pori County, n=2,983), and 11% in North Finland (Lapland, n=3,032). The
      prevalences in the ISAAC written questionnaire were 13, 20, 15, and 16%,
      respectively. The surveys were performed during winter, except in Helsinki where
      the survey was carried out mainly during the spring pollen season. During autumn,
      the prevalence in the written questionnaire in Helsinki was 16%. In multivariate
      analysis, boys had a lower prevalence than girls, and smokers a threefold higher
      prevalence than nonsmokers. In conclusion, the prevalence of childhood asthma is
      lower in Finland than in other European countries, and may be even lower in the
      eastern part of the country. In contrast to the results from some other European
      countries, prevalences were lower in the video than in the written questionnaire,
      which suggests that translating the word "wheezing" into other languages,
      including Finnish, may produce results that cannot be compared. The strong
      association of smoking with wheeze both in the video and written questionnaires
      should be considered in further analysis of the ISAAC study.

PMID- 9272921
TI  - Physician-diagnosed asthma and drug utilization in the European Community
      Respiratory Health Survey.
AB  - The aim of this analysis was to estimate the geographical variation in the
      prevalence of physician-diagnosed asthma and treatment practice for asthma in
      young adults. The results are based on an ecological analysis of 34 centres in 14
      countries, in which a total of 17,029 randomly selected subjects (52% females,
      age 20-48 yrs) underwent a structured interview and spirometry as part of the
      European Community Respiratory Health Survey. The sample was enriched with 2,903
      symptomatic subjects when investigating treatment in subjects with physician
      diagnosed asthma. The prevalence of physician-diagnosed asthma was highest in New
      Zealand and Australia (11-13%) and lowest in Erfurt, Germany (1.2%) and Spain
      (1.5-3.0%). The reported use of antiasthma medication in the last 12 months was
      also highest in New Zealand and Australia (12-16%) and correlated closely with
      the prevalence of diagnosed asthma (r=0.89, p<0.001). Herbal remedies against
      breathing problems had been used by 13% of subjects in Hamburg but the reported
      use of alternative remedies for breathing problems was low in most other centres.
      The use of inhaled anti-inflammatory drugs in subjects with physician-diagnosed
      asthma ranged from 49% in the UK to 17% in Italy and correlated with the
      prevalence of doctors' consultations within the last 12 months (r=0.66, p<0.05).
      The prevalence of anti-inflammatory treatment was positively related to the
      prevalence of nocturnal asthma symptoms (p<0.05). We conclude that there is a
      wide geographical variation in the prevalence of physician-diagnosed asthma and
      use of antiasthma medication. The geographical variation in the use of anti
      inflammatory drugs among individuals with diagnosed asthma may be related to
      variations in asthma severity, as well as differences in treatment practices
      between countries.

PMID- 9272922
TI  - Effect of ageing on peak expiratory flow variability and nocturnal exacerbations
      in bronchial asthma.
AB  - The aim of this study was to evaluate the role of ageing on variability of
      airflow obstruction and on the specific pattern of nocturnal exacerbations
      ("morning dipping" of peak expiratory flow (PEF)) in asthma. Two groups of stable
      asthmatics (Group A: 23 patients, aged 14-47 yrs; Group B: 20 patients, aged 53
      74 yrs), that were similar for duration of disease, degree of obstruction and
      response to bronchodilators, were studied. PEF was monitored four times daily for
      2 weeks, and amplitude of variation and "morning dip" were calculated. Both PEF
      amplitude and "morning dip" were greater in the older patients (p<0.005).
      Amplitude was negatively correlated with baseline forced expiratory volume in one
      second (FEV1) in both groups (p<0.01); multiple correlation with age, duration of
      disease, baseline FEV1 and degree of reversibility was significant in the older
      group only. Morning dip was inversely correlated to baseline FEV1 (p<0.01) and
      reversibility (p<0.05). Nocturnal symptoms were reported by all of the five Group
      A "dippers", but by only 6 of the 13 Group B "dippers" (p<0.04). Ageing
      contributes to increased variability of airway calibre in asthma. Aged patients
      are potentially at risk because functional evidence of nocturnal asthma may
      frequently be accompanied by a poor subjective awareness. Therefore, a more
      extensive practice of PEF monitoring is recommended in aged asthmatics.

PMID- 9272923
TI  - Do sputum eosinophils and ECP relate to the severity of asthma?
AB  - There is much evidence that eosinophils play an important role in bronchial
      epithelial damage in asthma by releasing cationic proteins. However, the extent
      to which eosinophil inflammation relates to indices of asthma severity in chronic
      stable asthma is still a matter of debate. We studied 46 clinically stable
      patients with mild to severe chronic asthma (forced expiratory volume in one
      second (FEV1) 50-126% of predicted value). The clinical severity of asthma was
      graded from 1 to 4 according to the Aas scoring system. Twelve normal subjects
      were also studied as controls. Induction of sputum was performed by hypertonic
      saline to determine differential cell count, and eosinophil cationic protein
      (ECP) by the so-called "plug technique". The concentration of ECP was measured by
      a fluoroimmunoassay. Bronchial hyperresponsiveness was recorded by inhaling
      progressive concentrations of histamine, and the concentration that caused a 20%
      decrease in FEV1 (PC20) was calculated. Sputum eosinophils (range 0-61%), sputum
      ECP (range 24-10,800 microg x L[-1]) and serum ECP (range 4-61 microg x L[-1])
      were significantly greater in asthmatics than in normal subjects, and
      distinguished the most severe group with the highest Aas score from the others.
      Sputum eosinophils and sputum ECP were strongly related to each other. The
      relationships between sputum or serum ECP and PC20 (range 0.016-7.5 mg x mL[-1]),
      and between sputum ECP and FEV1 were found to be weak. In conclusion, sputum
      outcomes of eosinophil activation and serum eosinophilic cationic protein appear
      to be useful indicators of disease. They do not accurately reflect current
      clinical or functional indices of asthma severity in chronic stable patients, and
      might therefore provide complementary data disease monitoring.

PMID- 9272924
TI  - Muscarinic contraction in isolated guinea-pig trachea and antagonism by
      noradrenaline.
AB  - In contrast to other muscarinic agonists, WAL 2014 FU does not induce
      bronchospasm in laboratory animals. The present investigation was intended to
      test the hypothesis that this is due to a particular susceptibility of the drug's
      effect to antagonism by catecholamines, as a result of partial M3-agonism. The
      tonic activity of the muscarinic agonists, aceclidine, arecoline, carbachol, McN
      A-343, RS 86, thiopilocarpine and WAL 2014 FU, was tested in groups of isolated
      tracheal muscle of the guinea-pig. Susceptibility to functional antagonism by
      beta-adrenoceptor stimulation was measured by the displacement of the
      concentration-force curves by 3 microM noradrenaline. Evaluation of the
      concentration-force relationship revealed differences in potency and intrinsic
      activity (carbachol-100%) ranging from 114% for arecoline to 36% for
      thiopilocarpine (WAL 2014 FU-63%). The catecholamine increased the concentration
      of agonist which induced 5% of the maximum effect achievable (EC05) values
      fivefold (carbachol) to more than 4,680 fold (thiopilocarpine) (WAL 2014 FU:
      2,860 fold). Regression analysis between the intrinsic activity of the seven
      compounds and the antagonistic effect of noradrenaline revealed a significant
      correlation (Spearman correlation coefficient (r[s])=-0.79; p=0.036). Inhibition
      of the effects of endogenous catecholamines by beta-adrenolysis with 50 microM
      toliprolol increased the maximal contraction induced by 1 mM WAL 2014 FU, but did
      not affect maximal contraction induced by 30 microM arecoline. Pretreatment with
      0.3-1.0 mM dibutyrylcyclic adenosine monophosphate (DBcAMP) shifted the
      concentration-response curves of arecoline, WAL 2014 FU and thiopilocarpine in a
      similar manner to noradrenaline. The results exclude an important contribution of
      adenylate cyclase-coupled M2-receptors to the susceptibility of tracheal
      contraction by muscarinic agonists to functional antagonism by noradrenaline, but
      emphasize the importance of intrinsic activity at the M3-receptors. The
      pronounced susceptibility of WAL 2014 FU-induced contraction to functional
      antagonism by beta-adrenoceptor activation provides an explanation for the
      failure of the drug to induce bronchospasm in vivo.

PMID- 9272925
TI  - Lung delivery of salbutamol by dry powder inhaler (Turbuhaler) and small volume
      antistatic metal spacer (Airomir CFC-free MDI plus NebuChamber).
AB  - As a worldwide ban on the use of chlorofluorocarbons (CFCs) in inhaler devices
      approaches, considerable attention has been focused on the production of CFC-free
      delivery devices. The aim of our study was to compare the delivery of salbutamol
      by dry powder inhaler (DPI), Turbuhaler and a CFC-free metered-dose inhaler
      (MDI), Airomir, used with a novel small volume metal spacer (NebuChamber). Ten
      healthy volunteers, mean (SEM) age 21 (0.7) yrs were studied in a randomized,
      single (investigator)-blind cross-over design. Single doses of 1,200 microg
      salbutamol, from Turbuhaler DPI and Airomir CFC-free MDI via a NebuChamber, were
      given as 12 sequential 100 microg inhalations over 6 min. The lung delivery of
      salbutamol was assessed by measuring the plasma salbutamol profile over the first
      20 min after inhalation. Plasma salbutamol concentration was expressed as maximal
      (Cmax) and average (Cav) value. Significant differences (p<0.001) were found
      between the NebuChamber (N) and the Turbuhaler (T) for salbutamol Cmax and Cav.
      This amounted to a 1.89 fold difference (95% CI 1.56-2.22) between these devices
      for Cmax, and a 1.78 fold difference (95% CI 1.42-2.15) for Cav. We have
      demonstrated that, in vivo, salbutamol from a chlorofluorocarbon-free metered
      dose inhaler given via a small volume metal spacer (NebuChamber) produces
      significantly greater delivery than from an efficient dry powder inhaler
      (Turbuhaler).

PMID- 9272926
TI  - Comparative efficacy and potency of ipratropium via Turbuhaler and pressurized
      metered-dose inhaler in reversible airflow obstruction.
AB  - Ipratropium bromide (IB), typically delivered by pressurized metered dose inhaler
      (pMDI), is used to treat patients with reversible airways obstruction. Use of the
      pMDI, unlike the Turbuhaler (TH), demands co-ordination of actuation with
      inspiration for efficient use. Two studies were carried out to compare the
      relative efficacy and potency of IB delivered by TH or pMDI. Both studies were of
      a randomized, double-blind and cross-over design. For the efficacy study, 15
      patients received a cumulative dose of 160 microg IB via TH or pMDI as doses of
      20, 20, 40 and 80 microg at 45 min intervals on two days. Forced expiratory
      volume in one second (FEV1) was measured prior to and 40 min after dosing. For
      the potency study, 33 patients received 10, 20 or 40 microg of IB via TH, 20
      microg IB via pMDI, or placebo, on five days. FEV1 was recorded prior to and 15
      360 min after dosing. For the efficacy study, there was no difference in FEV1
      response to a cumulative dose of IB via pMDI and TH. More than 80% of the maximum
      effect was seen at the lowest dose (20 microg of IB). Regarding the potency
      study, the FEV1 response to 20 microg IB administered via pMDI was similar to
      that of 10 microg via TH; 20 microg via TH was significantly more effective than
      20 microg via pMDI (p<0.05). In conclusion, the efficacy study showed that
      maximum FEV1 occurred at low doses of IB, negating any opportunity to identify
      differences between devices. The potency study indicated that the 10 microg dose
      via TH was of similar efficacy to the 20 microg dose via pMDI, confirming an
      efficacy ratio of 1.5-2.0:1 for the TH device.

PMID- 9272927
TI  - Dead space and slope indices from the expiratory carbon dioxide tension-volume
      curve.
AB  - The slope of phase 3 and three noninvasively determined dead space estimates
      derived from the expiratory carbon dioxide tension (PCO2) versus volume curve,
      including the Bohr dead space (VD,Bohr), the Fowler dead space (VD,Fowler) and
      pre-interface expirate (PIE), were investigated in 28 healthy control subjects,
      12 asthma and 29 emphysema patients (20 severely obstructed and nine moderately
      obstructed) with the aim to establish diagnostic value. Because breath volume and
      frequency are closely related to CO2 elimination, the recording procedures
      included varying breath volumes in all subjects during self-chosen/natural
      breathing frequency, and fixed frequencies of 10, 15 and 20 breaths x min(-1)
      with varying breath volumes only in the healthy controls. From the relationships
      of the variables with tidal volume (VT), the values at 1 L were estimated to
      compare the groups. The slopes of phase 3 and VD,Bohr at 1 L VT showed the most
      significant difference between controls and patients with asthma or emphysema,
      compared to the other two dead space estimates, and were related to the degree of
      airways obstruction. Discrimination between no-emphysema (asthma and controls)
      and emphysema patients was possible on the basis of a plot of intercept and slope
      of the relationship between VD,Bohr and VT. A combination of both the slope of
      phase 3 and VD,Bohr of a breath of 1 L was equally discriminating. The influence
      of fixed frequencies in the controls did not change the results. The conclusion
      is that Bohr dead space in relation to tidal volume seems to have diagnostic
      properties separating patients with asthma from patients with emphysema with the
      same degree of airways obstruction. Equally discriminating was a combination of
      both phase 3 and Bohr dead space of a breath of 1 L. The different
      pathophysiological mechanisms in asthma and emphysema leading to airways
      obstruction are probably responsible for these results.

PMID- 9272928
TI  - MDR1-Pgp 170 expression in human bronchus.
AB  - MDR1 P-glycoprotein (Pgp 170), a member of the adenosine triphosphate (ATP)
      binding cassette transporters, acts as an efflux pump for various hydrophobic
      agents, particularly for xenobiotics such as benzo(a)pyrene. It has also been
      shown to regulate cell-volume activated chloride channels. Pgp 170 could,
      therefore, be of particular importance in cellular mechanisms of defence in the
      airways and in the control of mucus layer composition. For these reasons, we
      evaluated the precise localization of Pgp 170 in human adult airways. Fresh non
      neoplastic bronchial specimens were collected from 33 patients (26 smokers, four
      exsmokers and three nonsmokers) who underwent surgery for lung carcinoma. The
      presence of MDR1 messenger ribonucleic acid (mRNA) was demonstrated by reverse
      transcriptase chain reaction (RT-PCR) in bronchial epithelial cells collected by
      gentle scraping from either smokers, exsmokers or nonsmokers. Immunodetection of
      Pgp 170 using a panel of monoclonal antibodies (MRK16, JSB1, C219, C494) was
      performed either on cryostat or paraffin-embedded sections of histologically
      normal bronchial tissue. Pgp 170 was constantly detected with intense labelling
      at the apical surface of ciliated epithelial cells from the surface epithelium or
      ciliated collecting ducts, and on apical and lateral surfaces of serous cells
      from bronchial glands. No staining of mucus-secreting cells was observed. Pgp 170
      was also demonstrated at the luminal surface of endothelial cells of bronchial
      capillaries. In conclusion, the expression of MDR1 P-glycoprotein in bronchial
      structures, particularly at the epithelial apical surface, suggests important
      roles for this transmembrane protein in human airways.

PMID- 9272929
TI  - Neutral endopeptidase activity in newborn and adult rabbit tracheas.
AB  - Neutral endopeptidase (NEP, E.C. 3.4.24.11), a widely distributed ectoenzyme,
      cleaves and inactivates a variety of biologically active peptides, including the
      tachykinin, substance P (SP). This study was undertaken to determine whether the
      modulation of SP airway smooth muscle contraction by NEP is age-dependent. We
      studied the contractile response of isolated tracheal rings from newborn and 120
      day old New Zealand white rabbits. We measured NEP activity and determined
      immunoreactive NEP content in tracheal membrane preparations. NEP activity was
      then localized histochemically in sections of rabbit tracheas. In the presence of
      the NEP inhibitor, SCH 32615, the contractile response of isolated tracheal rings
      to SP was increased both in the newborn and 120 day old rabbits. However, the
      increase was greatest in the newborn animals. NEP activity in tracheal membrane
      preparations increased fivefold between the newborn and 120 day old rabbits.
      Western blot analysis also revealed a significant increase in the immunoreactive
      NEP content of these tracheal membrane preparations between the newborn and 120
      day old rabbits. NEP activity, localized histochemically, was most intense in the
      epithelial region of the newborn animals, with a shift of activity to the
      subepithelial region with age. The prominent epithelial localization of neutral
      endopeptidase in the tracheas of these 1 day old rabbits, which we have shown to
      have relatively low neutral endopeptidase activity, suggests that the location of
      neutral endopeptidase in the airway, including proximity to relevant substance P
      receptors, may be critical to its function.

PMID- 9272930
TI  - Alterations of lung structure in experimental diabetes, and diabetes associated
      with hyperlipidaemia in hamsters.
AB  - Since hyperglycaemia is known to affect normal pulmonary physiology and
      biochemistry and few structure-function correlations have been reported, we
      designed experiments on hamsters subjected to streptozotocin-induced diabetes or
      diabetes associated with hyperlipidaemia, and investigated the impact of these
      conditions on the lung structure. At time intervals ranging 2-24 weeks from the
      inception of disease (without correcting blood glucose with insulin), the animals
      were sacrificed, and plasma glucose and cholesterol assayed. The lung was
      processed for electron microscopy, and the structural changes of the capillary
      and venular endothelium, of epithelial cells, and interstitium were examined. In
      diabetic animals, especially after 6 weeks of disease, a gradual narrowing of
      approximately 35% of the capillaries and approximately 30% of the alveoli, and
      hyperplasia of the extracellular matrix, rich in collagen bundles, were observed.
      Frequently, capillaries contained adherent intravascular macrophages suggestive
      of an inflammatory process. The capillary endothelium was characterized by
      numerous plasmalemmal vesicles, often fused, well-developed synthesizing
      apparatus (endoplasmic reticulum and Golgi complex) and cytoskeleton, and an
      uneven distribution of the anionic sites on the luminal plasmalemma. The venular
      endothelium was particularly rich in Weibel-Palade bodies. The alveolar
      epithelium was often collapsed, compressing surfactant within the airspace. The
      lung interstitium was apparently enlarged, and the fibroblasts and contractile
      interstitial cells frequently contained lipid droplets. These alterations were
      more pronounced and occurred at a faster rate (4 weeks) in diabetes associated
      with hyperlipidaemia. The structural modifications reported in this study support
      the functional disturbances observed in association with hyperglycaemia,
      sustaining the conclusion that the lung is an organ affected by diabetes.

PMID- 9272931
TI  - Paired phrenic nerve stimuli for the detection of diaphragm fatigue in humans.
AB  - The transdiaphragmatic pressure (Pdi) elicited by paired bilateral phrenic nerve
      stimulation may be viewed as the sum of the Pdi values produced by the first (t1)
      and second (t2) stimulus. The Pdi at t2 (P[di,t2]) is a function of the
      interstimulus interval. A reduction in the ratio obtained by dividing Pdi,t2 at
      10 Hz (P[di,t2,10]) by Pdi at 100 Hz (P[di,t2,100]) (t2(10:100)) has been
      proposed as a test of low frequency diaphragm fatigue. The aim of the present
      study was to establish whether this change could also be detected using paired
      cervical magnetic nerve stimulation (pCMS), and whether t2(10:100) was influenced
      by lung volume. We studied healthy subjects at functional residual capacity
      (FRC), at 0.5 and 1.0 L below FRC, and at 0.5, 1.0 and 1.5 L above FRC. The
      subjects were then subjected to a fatiguing protocol (2 min of maximal isocapnic
      ventilation (MIV)). Studies were repeated at FRC 20 and 60 min after MIV and
      between these times at 1.0 L below and 1.5 L above FRC. In the unfatigued state,
      t2(10:100) had a negative relationship with increasing lung volume (r2=0.98,
      p=0.002). After MIV there was a fall in the Pdi elicited by a single stimulus
      (mean fall at 20 min 17.9% and at 60 min 14.6%, p<0.03 for both). t2(10:100) fell
      by a mean 28.1% after 20 min and mean 22.9% at 60 min (p<0.03 for both). This
      change was mainly mediated by a fall in the P[di,t2,10]. The t2(10:100) was not
      able to distinguish between fatigue and acute hyperinflation. We conclude that
      paired cervical magnetic nerve stimulation may be used to detect low frequency
      diaphragm fatigue but that it remains important to control for lung volume.

PMID- 9272932
TI  - Laser monitoring of chest wall displacement.
AB  - We developed a prototype laser monitor, consisting of a single laser sensor, to
      observe chest wall displacement during respiration. With this monitor,
      respiratory waveforms are expressed as an anterioposterior motion of the chest
      wall. The purpose of this study was to examine the characteristics and
      performance of this prototype. Performance was assessed: 1) under static
      conditions; 2) using a lung model ventilated in both conventional and high
      frequency oscillation (HFOV) modes; and 3) during spontaneous breathing in normal
      adults. In vitro, the monitor performed well both under static conditions and
      during mechanical ventilation. Reliable "respiratory" wave forms, with no
      frequency-dependent change in the relationship between displacement and volume,
      were produced during both conventional ventilation and HFOV at 15 Hz. In vivo,
      abdominal displacement, measured in the midline, was linearly correlated with the
      tidal volume signal integrated from flow. The waveforms produced by the monitor
      were adequate for monitoring respiration and for calculating respiratory timing
      variables. While a single laser sensor is unlikely to be sufficient for
      monitoring respiration in spontaneously breathing subjects, the performance of
      the prototype monitor was sufficiently impressive to encourage further
      development and further study of this type of truly noninvasive respiratory
      monitor.

PMID- 9272933
TI  - Influence of endotracheal tube diameter on forced deflation flow-volume curves in
      rhesus monkeys.
AB  - The forced deflation (FD) technique is the recommended gold standard to generate
      forced expiratory vital capacity (FVC) curves and to measure maximum expiratory
      flow-volume (MEFV) relationships in intubated infants and children. However, the
      influence of the endotracheal tube (ETT) on the site of flow limitation, the
      shape and the analysis of the resultant MEFV curves have not been defined. Nine
      anaesthetized (thiopentone, 8 mg x kg(-1) x h(-1)) rhesus monkeys (mean weight
      (+/-SEM) 10+/-1 kg) were intubated consecutively with ETTs of different internal
      diameters (ID 3.0-5.5 mm, at intervals of 0.5 mm); the largest representing the
      appropriate ETT size for the animal. Quadruplicate MEFV curves were generated by
      FD using the standard +40 cmH2Oinsp/-40 cmH2Oexp pressures and recorded at each
      ETT diameter. The effect of the different ETT diameters on the FD flow-volume
      curve was analysed by comparing maximum expiratory flows at isovolume points at
      50, 25 and 10% FVC (MEF50, MEF25 and MEF10, respectively). The shape of the
      resulting MEFV curves could be divided into an initial horizontal part (tube
      dependent), and a final descending slope (airway-dependent). No difference in FVC
      occurred irrespective of the ETT size (p>0.05 by analysis of variance (ANOVA)).
      MEF50 increased with increasing tube diameter (p<0.05). MEF25 remained unchanged
      using ETTs which were less than 1.5 mm smaller than the largest ETT. Smaller ETTs
      resulted in significantly reduced MEF25 (p<0.05). MEF10 was not influenced by the
      ETT size. We conclude that maximum expiratory flows measured by the forced
      deflation technique are not influenced by an appropriately sized endotracheal
      tube at lung volumes below 25% forced vital capacity in our monkey model with
      normal lungs. We postulate that the effect of endotracheal tubes on maximum
      expiratory flow volume curves in intubated infants might be of similar or even
      smaller magnitude, which remains to be established.

PMID- 9272934
TI  - Limits of commercial molecular tests for diagnosis of pulmonary tuberculosis.
AB  - Several studies report high specificity, but variable sensitivity, of Amplified
      Mycobacterium tuberculosis Direct Test (AMTDT, Gen-Probe) based on ribosomal
      ribonucleic acid (rRNA) amplification and Amplicor Mycobacterium tuberculosis
      test (Amplicor, Roche) based on deoxyribonucleic acid (DNA) amplification for
      diagnosis of pulmonary tuberculosis. We have retrospectively evaluated these
      assays on selected acid-fast bacilli (AFB)-positive and -negative smear specimens
      and compared the results obtained from nucleic acid amplification with those of
      AFB staining of semi-quantitative cultures as determined by radiometric Bactec
      and Lowenstein-Jensen cultures. In comparison to cultures, Amplicor and AMTDT
      assays exhibited identical overall sensitivities of 80%, while the staining had a
      lower sensitivity of 62%. The sensitivities of Amplicor and AMTDT were 98% and
      100%, respectively, for the AFB-positive specimens, and 50 and 46%, respectively
      for the AFB-negative specimens in comparison to cultures. The sensitivities of
      both assays appeared similar, and were directly related to the number of bacilli
      in the specimens studied. The low sensitivity (50%) for smear-negative specimens
      showed that current amplification assays may be unsuitable to replace cultures
      for diagnosis of tuberculosis. The decision to perform these molecular techniques
      should result from close co-operation between clinicians and microbiologists,
      taking into account the sensitivity results reported here, as well as the expense
      of the assays.

PMID- 9272935
TI  - Molecular diagnosis of tuberculosis: current clinical validity and future
      perspectives.
AB  - The rapid development and availability of a variety of new molecular genetic
      technologies present the clinician with an array of options for the accurate
      diagnosis of infectious diseases. This is particularly the case for tuberculosis,
      since molecular methods have been rapidly introduced into all working areas of
      the mycobacteriology laboratory. Nucleic acid amplification methods to detect
      Mycobacterium tuberculosis in clinical specimens are increasingly used as a tool
      to diagnose tuberculosis. The bulk of recently available data from clinical
      evaluations performed under routine laboratory conditions indicate that these
      molecular methods are rapid and sensitive, but yet inferior, to culture with
      regard to sensitivity and specificity. Therefore, until gene amplification tests
      have proved to be reliable and quality control procedures exist, their clinical
      validity remains controversial. Consequently, definition of selected clinical
      applications of gene amplification to routine diagnosis of tuberculosis is
      important and need to be discussed. This review will focus on the clinical role
      of molecular methods in the direct detection and diagnosis of M. tuberculosis in
      clinical samples. In addition, molecular genetic approaches designed to determine
      drug susceptibility and to discriminate strains below the species level will be
      outlined and discussed in terms of their current and future clinical
      applicability.

PMID- 9272936
TI  - The role of tachykinin receptor antagonists in the prevention of bronchial
      hyperresponsiveness, airway inflammation and cough.
AB  - Several recent observations suggest that tachykinins, such as substance P and
      neurokinin A, might be involved in the pathogenesis of bronchopulmonary
      alterations. Progress in investigations on the physiological and pathological
      roles of tachykinins has been greatly facilitated by the availability of a number
      of highly selective nonpeptide antagonists for tachykinin neurokinin 1, 2 and 3
      (NK1, NK2 and NK3) receptors. The use of selective tachykinin NK2 receptor
      antagonists suggests that tachykinin NK2 receptor stimulation plays an important
      role in the development of airway hyperresponsiveness in the guinea-pig. Others
      studies have also indicated that tachykinin NK1-receptors are involved in
      immediate or delayed neurogenic inflammation including microvascular leakage and
      the subsequent increase in plasma protein extravasation. A role for the sensory
      neuropeptide system has also been proposed in cough, as shown by the observation
      that the antitussive effect of tachykinin NK2 receptor antagonists has clearly
      been demonstrated in several experimental conditions, but the effect of
      tachykinin NK1 receptor antagonists is still debated. Taken together, the results
      obtained with the various selective receptor antagonists provide pharmacological
      evidence that tachykinins play a role in delayed bronchopulmonary alterations and
      suggest that tachykinin receptor antagonists may be useful for investigating
      mechanisms and possibly reducing airway functional alterations in asthmatic
      patients.

PMID- 9272937
TI  - Pleural diseases related to metastatic malignancies.
AB  - Pleural effusions associated with malignancy (either malignant or paramalignant)
      pose diagnostic and therapeutic dilemmas for the clinician. This article reviews
      the common causes of malignant and paramalignant pleural effusions, pathogenesis,
      clinical presentation, chest radiography, pleural fluid characteristics,
      diagnosis, prognosis, and treatment. Talc, used either by poudrage or slurry, is
      the most effective agent used for pleurodesis. Talc, which needs to be
      sterilized, has no clinically important immediate, short-term or long-term
      adverse effects.

PMID- 9272938
TI  - Lung mucus: a clinician's view.
AB  - Respiratory mucus represents the products derived from secretion of the
      submucosal glands and the goblet cells. Accumulation of mucus in the airway tree
      may be caused by an increased volume of mucus produced, and also by decreased
      clearance due to defects in the ciliary clearance apparatus. Hypersecretion of
      mucus contributes to the morbidity of airway diseases by predisposing patients to
      respiratory infections, and contributing to airflow obstruction and to patients'
      discomfort. There is a significant association between chronic production of
      mucus and an increased risk of mortality. Also the degree of airway obstruction
      is related to the physical properties of the sputum. Observation of chronic
      bronchitic sputum can reveal important clinical information concerning the type
      and level of the inflammatory process, the physical properties of the material,
      the extent of bronchial mucosal damage, and the identification of pathogenic
      microorganisms that may be present. The management of mucous hypersecretion can
      be undertaken in two main ways: firstly, improved clearance by physical methods;
      and, secondly, by pharmacological methods.

PMID- 9272939
TI  - Rhinitis caused by ninhydrin develops into occupational asthma.
AB  - Ninhydrin (2,2-dihydroxy-1,3-indanedione or 1,2,3-triketo-hydrindene hydrate) is
      a chemical used in the detection of free amino and carboxyl groups in proteins
      and peptides. Allergic, immunoglobulin E (IgE)-mediated rhinitis caused by
      ninhydrin was diagnosed earlier in a 41 yr old woman working as a laboratory
      technician in a forensic laboratory. Despite handling ninhydrin only in a flow
      cabinet, symptoms of dyspnoea developed 6 months later. Peak flow was found to
      vary by 20% during working days. In the specific inhalation challenge it was
      shown that occupational asthma had also developed due to continuing slight
      exposure to ninhydrin. The titre of ninhydrin-specific IgE also increased from
      0.6 to 1.1 kU x L(-1) in the follow-up. This case stresses the importance of
      cessation of allergen exposure in occupational allergic rhinitis, in order to
      prevent asthma.

PMID- 9272940
TI  - Bilateral diaphragmatic paralysis--a rare cause of acute respiratory failure
      managed with nasal mask bilevel positive airway pressure (BiPAP) ventilation.
AB  - A 68 yr old woman presented with acute respiratory failure. She was suspected of
      having a phrenic-diaphragmatic impairment, without evidence of an intrinsic lung
      disease or generalized neuromuscular disorder, after 3 weeks of prolonged
      mechanical ventilation. A series of studies, including fluoroscopy, phrenic nerve
      stimulation test and diaphragmatic electromyography, was performed before the
      diagnosis of bilateral diaphragmatic paralysis (BDP) was confirmed. The patient
      was successfully weaned from the conventional mechanical ventilator, and was
      placed on nasal mask bi-level positive airway pressure (BiPAP) ventilation. A
      high degree of clinical suspicion of bilateral diaphragmatic paralysis should
      always be raised in patients suffering respiratory failure without definite
      predisposing factors. Weaning with noninvasive nasal mask ventilation should be
      tried first instead of direct tracheostomy.

PMID- 9272941
TI  - Metastatic pulmonary calcification after renal transplantation.
AB  - Metastatic pulmonary calcifications, unlike dystrophic calcifications, occur in
      the normal healthy lung. The radiological pattern is quite specific. The disease
      is commonly described in chronic renal failure with calcium disorders. The
      prognosis is totally unpredictable. In 1992, a 50 yr old man underwent a
      successful renal transplantation during the final stage of chronic renal failure.
      He subsequently developed asymptomatic diffuse nodular opacities, that were
      discovered in 1995. An open lung biopsy confirmed the diagnosis of metastatic
      pulmonary calcification. There was no calcium disorder in this patient. In
      contrast to the benign course of pulmonary calcification in most patients, some
      fulminant pulmonary calcifications complicating renal transplantation or
      hypercalcaemia have been described. Radiographic identification of such entities
      is important to permit correction of calcium disorders. Otherwise, the condition
      is a potentially progressive and fatal cause of respiratory failure.

PMID- 9272942
TI  - Lung volume equipment and infection control. ERS/ATS Workshop Report Series.
      European Respiratory Society/American Thoracic Society.
AB  - As part of the consensus workshop regarding lung volume measurements for the
      American Thoracic Society and European Respiratory Society, this background paper
      reviews mechanisms and risks of cross-infection resultant from performing
      measurements of absolute lung volumes either by body plethysmography, gas
      dilution, or gas wash-out techniques. Published reports of infection attributable
      to the performance of lung volume measurements are extremely rare. Nevertheless,
      because some infectious agents could be transmitted during measurements of lung
      volumes, and because of widespread concerns both of patients and some medical
      personnel about the risks of transmission of infections during inspiration from
      equipment used by other patients, a variety of measures have been advocated to
      minimize the risks of cross-infection. Workshop participants were divided in
      opinion about whether such testing does indeed pose significant risk of cross
      infection, and also could not agree regarding optimal measures to prevent cross
      infection. Although there is conflicting information regarding the efficacy of
      particulate filters for protecting cross-contamination of downstream equipment
      and tubing, the author recommends that such filters be used when making lung
      volume measurements, but only if the filter has acceptably low resistance (e.g.
      <0.15 kPa x L(-1) x s (1.5 cmH2O x L(-1) x s)), and the measurements are adjusted
      for the impact of the added resistance and dead space.

PMID- 9272943
TI  - Is pulmonary arterial impedance affected by breathing?

PMID- 9272944
TI  - Mouse-chick chimera: a developmental model of murine neurogenic cells.
AB  - Chimeras were prepared by transplanting fragments of neural primordium from 8- to
      8.5- and 9-day postcoital mouse embryos into 1.5- and 2-day-old chick embryos at
      different axial levels. Mouse neuroepithelial cells differentiated in ovo and
      organized to form the different cellular compartments normally constituting the
      central nervous system. The graft also entered into the development of the
      peripheral nervous system through migration of neural crest cells associated with
      mouse neuroepithelium. Depending on the graft level, mouse crest cells
      participated in the formation of various derivatives such as head components,
      sensory ganglia, orthosympathetic ganglionic chain, nerves and neuroendocrine
      glands. Tenascin knockout mice, which express lacZ instead of tenascin and show
      no tenascin production (Saga, Y., Yagi, J., Ikawa, Y., Sakakura, T. and Aizawa,
      S. (1992) Genes and Development 6, 1821-1838), were specifically used to label
      Schwann cells lining nerves derived from the implant. Although our experiments do
      not consider how mouse neural tube can participate in the mechanism required to
      maintain myogenesis in the host somites, they show that the grafted neural tube
      behaves in the same manner as the chick host neural tube. Together with our
      previous results on somite development (Fontaine-Perus, J., Jarno, V., Fournier
      Le Ray, C., Li, Z. and Paulin, D. (1995) Development 121, 1705-1718), this study
      shows that chick embryo constitutes a privileged environment, facilitating access
      to the developmental potentials of normal or defective mammalian cells. It allows
      the study of the histogenesis and precise timing of a known structure, as well as
      the implication of a given gene at all equivalent mammalian embryonic stages.

PMID- 9272945
TI  - Xenopus msx1 mediates epidermal induction and neural inhibition by BMP4.
AB  - Epidermal fate in Xenopus ectoderm has been shown to be induced by a secreted
      growth factor, Bone Morphogenetic Protein 4 (BMP4). However, the molecular
      mechanism mediating this response is poorly understood. Here, we show that the
      expression of the homeobox gene, msx1, is an immediate early response to BMP4 in
      Xenopus embryos. The timing of expression and embryonic distribution of msx1
      parallel those described for BMP4. Moreover, overexpression of msx1 in early
      Xenopus embryos leads to their ventralization as described for BMP4. Consistent
      with mediating a BMP type of signaling, overexpression of msx1 is sufficient to
      induce epidermis in dissociated ectoderm cells, which would otherwise form neural
      tissue. Finally, msx1 can also rescue neuralization imposed by a dominant
      negative BMP receptor (tBR) in ectodermal explants. We propose that Xenopus msx1
      acts as a mediator of BMP signaling in epidermal induction and inhibition of
      neural differentiation.

PMID- 9272946
TI  - Loss-of-function mutations in the maize homeobox gene, knotted1, are defective in
      shoot meristem maintenance.
AB  - The product of the maize homeobox gene, knotted1 (kn1), localizes to the nuclei
      of cells in shoot meristems, but is absent from portions of the meristem where
      leaf primordia or floral organs initiate. Recessive mutant alleles of kn1 were
      obtained by screening for loss of the dominant leaf phenotype in maize. Mutant
      kn1 alleles carrying nonsense, splicing and frame shift mutations cause severe
      inflorescence and floral defects. Mutant tassels produce fewer branches and
      spikelets. Ears are often absent, and when present, are small with few spikelets.
      In addition, extra carpels form in female florets and ovule tissue proliferates
      abnormally. Less frequently, extra leaves form in the axils of vegetative leaves.
      These mutations reveal a role for kn1 in meristem maintenance, particularly as it
      affects branching and lateral organ formation.

PMID- 9272947
TI  - Defects in glucuronate biosynthesis disrupt Wingless signaling in Drosophila.
AB  - In vitro experiments suggest that glycosaminoglycans (GAGs) and the proteins to
      which they are attached (proteoglycans) are important for modulating growth
      factor signaling. However, in vivo evidence to support this view has been
      lacking, in part because mutations that disrupt the production of GAG polymers
      and the core proteins have not been available. Here we describe the
      identification and characterization of Drosophila mutants in the suppenkasper
      (ska) gene. The ska gene encodes UDP-glucose dehydrogenase which produces
      glucuronic acid, an essential component for the synthesis of heparan and
      chondroitin sulfate. ska mutants fail to put heparan side chains on proteoglycans
      such as Syndecan. Surprisingly, mutant embryos produced by germ-line clones of
      this general metabolic gene exhibit embryonic cuticle phenotypes strikingly
      similar to those that result from loss-of-function mutations in genes of the
      Wingless (Wg) signaling pathway. Zygotic loss of ska leads to reduced growth of
      imaginal discs and pattern defects similar to wg mutants. In addition, genetic
      interactions of ska with wg and dishevelled mutants are observed. These data
      demonstrate the importance of proteoglycans and GAGs in Wg signaling in vivo and
      suggest that Wnt-like growth factors may be particularly sensitive to
      perturbations of GAG biosynthesis.

PMID- 9272948
TI  - Mouse Dll3: a novel divergent Delta gene which may complement the function of
      other Delta homologues during early pattern formation in the mouse embryo.
AB  - Mouse delta-like 3 (Dll3), a novel vertebrate homologue of the Drosophila gene
      Delta was isolated by a subtracted library screen. In Drosphila, the Delta/Notch
      signalling pathway functions in many situations in both embryonic and adult life
      where cell fate specification occurs. In addition, a patterning role has been
      described in the establishment of the dorsoventral compartment boundary in the
      wing imaginal disc. Dll3 is the most divergent Delta homologue identified to
      date. We confirm that Dll3 can inhibit primary neurogenesis when ectopically
      expressed in Xenopus, suggesting that it can activate the Notch receptor and
      therefore is a functional Delta homologue. An extensive expression study during
      gastrulation and early organogenesis in the mouse reveals a diverse and dynamic
      pattern of expression. The three major sites of expression implicate Dll3 in
      somitogenesis and neurogenesis and in the production of tissue from the primitive
      streak and tailbud. A careful comparison of Dll3 and Dll1 expression by double
      RNA in situ hybridisation demonstrates that these genes have distinct patterns of
      expression, but implies that together they operate in many of the same processes.
      We postulate that during somitogenesis Dll3 and Dll1 coordinate in establishing
      the intersomitic boundaries. We confirm that, during neurogenesis in the spinal
      cord, Dll1 and Dll3 are expressed by postmitotic cells and suggest that
      expression is sequential such that cells express Dll1 first followed by Dll3. We
      hypothesise that Dll1 is involved in the release of cells from the precursor
      population and that Dll3 is required later to divert neurons along a specific
      differentiation pathway.

PMID- 9272949
TI  - Early- and late-migrating cranial neural crest cell populations have equivalent
      developmental potential in vivo.
AB  - We present the first in vivo study of the long-term fate and potential of early
      migrating and late-migrating mesencephalic neural crest cell populations, by
      performing isochronic and heterochronic quail-to-chick grafts. Both early- and
      late-migrating populations form melanocytes, neurons, glia, cartilage and bone in
      isochronic, isotopic chimeras, showing that neither population is lineage
      restricted. The early-migrating population distributes both dorsally and
      ventrally during normal development, while the late-migrating population is
      confined dorsally and forms much less cartilage and bone. When the late-migrating
      population is substituted heterochronically for the early-migrating population,
      it contributes extensively to ventral derivatives such as jaw cartilage and bone.
      Conversely, when the early-migrating population is substituted heterochronically
      for the late-migrating population, it no longer contributes to the jaw skeleton
      and only forms dorsal derivatives. When the late-migrating population is grafted
      into a late-stage host whose neural crest had previously been ablated, it
      migrates ventrally into the jaws. Thus, the dorsal fate restriction of the late
      migrating mesencephalic neural crest cell population in normal development is due
      to the presence of earlier-migrating neural crest cells, rather than to any
      change in the environment or to any intrinsic difference in migratory ability or
      potential between early- and late-migrating cell populations. These results
      highlight the plasticity of the neural crest and show that its fate is determined
      primarily by the environment.

PMID- 9272950
TI  - Genetically engineered mice demonstrate that adenosine deaminase is essential for
      early postimplantation development.
AB  - Adenosine deaminase (ADA) is an essential enzyme of purine metabolism that is
      enriched at the maternal-fetal interface of mice throughout postimplantation
      development. During early postimplantation stages Ada is highly expressed in both
      maternally derived decidual cells and zygotically derived trophoblast cells. For
      the current study we utilized genetically modified mice to delineate the relative
      contribution and importance of decidual and trophoblast ADA at the maternal-fetal
      interface. In females genetically engineered to lack decidual ADA a striking
      pattern of expression was revealed in giant trophoblast cells that surround the
      early postimplantation embryo. Embryos within gestation sites lacking both
      decidual and trophoblast ADA died during the early postimplantation period,
      whereas expression in trophoblast cells alone was sufficient for survival through
      this period. Severe disturbances in purine metabolism were observed in gestation
      sites lacking decidual ADA, including the accumulation of the potentially toxic
      ADA substrates adenosine and 2'-deoxyadenosine. These experiments provide genetic
      evidence that Ada expression at the maternal-fetal interface is essential for
      early postimplantation development in mice.

PMID- 9272951
TI  - The role of the msh homeobox gene during Drosophila neurogenesis: implication for
      the dorsoventral specification of the neuroectoderm.
AB  - Development of the Drosophila central nervous system begins with the delamination
      of neural and glial precursors, called neuroblasts, from the neuroectoderm. An
      early and important step in the generation of neural diversity is the
      specification of individual neuroblasts according to their position. In this
      study, we describe the genetic analysis of the msh gene which is likely to play a
      role in this process. The msh/Msx genes are one of the most highly conserved
      families of homeobox genes. During vertebrate spinal cord development, Msx genes
      (Msx1-3) are regionally expressed in the dorsal portion of the developing
      neuroectoderm. Similarly in Drosophila, msh is expressed in two longitudinal
      bands that correspond to the dorsal half of the neuroectoderm, and subsequently
      in many dorsal neuroblasts and their progeny. We showed that Drosophila msh loss
      of-function mutations led to cell fate alterations of neuroblasts formed in the
      dorsal aspect of the neuroectoderm, including a possible dorsal-to-ventral fate
      switch. Conversely, ectopic expression of msh in the entire neuroectoderm
      severely disrupted the proper development of the midline and ventral neuroblasts.
      The results provide the first in vivo evidence for the role of the msh/Msx genes
      in neural development, and support the notion that they may perform
      phylogenetically conserved functions in the dorsoventral patterning of the
      neuroectoderm.

PMID- 9272952
TI  - Temporally-regulated retinoic acid depletion produces specific neural crest,
      ocular and nervous system defects.
AB  - Both retinoid receptor null mutants and classic nutritional deficiency studies
      have demonstrated that retinoids are essential for the normal development of
      diverse embryonic structures (e.g. eye, heart, nervous system, urogenital tract).
      Detailed analysis of retinoid-modulated events is hampered by several limitations
      of these models, including that deficiency or null mutation is present throughout
      gestation, making it difficult to isolate primary effects, and preventing
      analysis beyond embryolethality. We developed a mammalian model in which retinoid
      dependent events are documented during distinct targeted windows of
      embryogenesis. This was accomplished through the production of vitamin A-depleted
      (VAD) female rats maintained on sufficient oral retinoic acid (RA) for growth and
      fertility. After mating to normal males, these RA-sufficient/VAD females were
      given oral RA doses which allowed for gestation in an RA-sufficient state;
      embryogenesis proceeded normally until retinoids were withdrawn dietarily to
      produce a sudden, acute retinoid deficiency during a selected gestational window.
      In this trial, final RA doses were administered on E11.5, vehicle at E12.5, and
      embryos analyzed on E13.5; during this 48 hour window, the last RA dose was
      metabolized and embryos progressed in a retinoid-deficient state. RA-sufficient
      embryos were normal. Retinoid-depleted embryos exhibited specific malformations
      of the face, neural crest, eyes, heart, and nervous system. Some defects were
      phenocopies of those seen in null mutant mice for RXR alpha(-/-), RXR alpha(-/
      )/RAR alpha(-/-), and RAR alpha(-/-)/RAR gamma(-/-), confirming that RA
      transactivation of its nuclear receptors is essential for normal embryogenesis.
      Other defects were unique to this deficiency model, showing that complete ligand
      'knock-out' is required to see those retinoid-dependent events previously
      concealed by receptor functional redundancy, and reinforcing that retinoid
      receptors have separate yet overlapping contributions in the embryo. This model
      allows for precise targeting of retinoid form and deficiency to specific
      developmental windows, and will facilitate studies of distinct temporal events.

PMID- 9272953
TI  - klumpfuss, a Drosophila gene encoding a member of the EGR family of transcription
      factors, is involved in bristle and leg development.
AB  - The klumpfuss (klu) transcription unit in Drosophila gives rise to two different
      transcripts of 4.5 and 4.9 kb, both of which encode a putative transcription
      factor with four zinc-finger motifs of the C2H2 class. Zinc-finger 2-4 are
      homologous to those of the proteins of the EGR transcription factor family. As in
      the case of the most divergent member of the family, the Wilms' tumor suppressor
      gene (WT-1), klu contains an additional zinc finger, which is only distantly
      related. Loss of klumpfuss function is semilethal and causes a variety of defects
      in bristles and legs of adults, as well as in mouth hooks and brains of larvae.
      Analysis of the mutants indicates that klumpfuss is required for proper
      specification and differentiation of a variety of cells, including the sensory
      organ mother cells and those of the distal parts of tarsal segments.

PMID- 9272954
TI  - HOXD4 and regulation of the group 4 paralog genes.
AB  - From an evolutionary perspective, it is important to understand the degree of
      conservation of cis-regulatory mechanisms between paralogous Hox genes. In this
      study, we have used transgenic analysis of the human HOXD4 locus to identify one
      neural and two mesodermal 3' enhancers that are capable of mediating the proper
      anterior limits of expression in the hindbrain and paraxial mesoderm (somites),
      respectively. In addition to directing expression in the central nervous system
      (CNS) up to the correct rhombomere 6/7 boundary in the hindbrain, the neural
      enhancer also mediates a three rhombomere anterior shift from this boundary in
      response to retinoic acid (RA), mimicking the endogenous Hoxd4 response. We have
      extended the transgenic analysis to Hoxa4 identifying mesodermal, neural and
      retinoid responsive components in the 3' flanking region of that gene, which
      reflect aspects of endogenous Hoxa4 expression. Comparative analysis of the
      retinoid responses of Hoxd4, Hoxa4 and Hoxb4 reveals that, while they can be
      rapidly induced by RA, there is a window of competence for this response, which
      is different to that of more 3' Hox genes. Mesodermal regulation involves
      multiple regions with overlapping or related activity and is complex, but with
      respect to neural regulation and response to RA, Hoxb4 and Hoxd4 appear to be
      more closely related to each other than Hoxa4. These results illustrate that much
      of the general positioning of 5' and 3' flanking regulatory regions has been
      conserved between three of the group 4 paralogs during vertebrate evolution,
      which most likely reflects the original positioning of regulatory regions in the
      ancestral Hox complex.

PMID- 9272955
TI  - Medaka spalt acts as a target gene of hedgehog signaling.
AB  - In vertebrates, pattern formation in the eye, central nervous system, somites,
      and limb depends on hedgehog activity, but a general target gene controlled by
      hedgehog in all these signaling centers has remained largely elusive. The medaka
      fish gene spalt encodes a zinc-finger transcription factor, which is expressed in
      all known hedgehog signaling centers of the embryo and in the organizer region at
      the midbrain-hindbrain boundary. We show that the spalt expression domains expand
      in response to ectopic hedgehog activity and narrow in the presence of protein
      kinase A activity, an antagonist of hedgehog signaling, indicating that spalt is
      a hedgehog target gene. Our results also suggest a signaling mechanism for
      anterior-posterior patterning of the vertebrate brain that controls spalt
      expression at the midbrain-hindbrain boundary in a protein kinase A dependent
      manner likely to involve an unknown member of the hedgehog family.

PMID- 9272956
TI  - Zebrafish vasa homologue RNA is localized to the cleavage planes of 2- and 4-cell
      stage embryos and is expressed in the primordial germ cells.
AB  - Identification and manipulation of the germ line are important to the study of
      model organisms. Although zebrafish has recently emerged as a model for
      vertebrate development, the primordial germ cells (PGCs) in this organism have
      not been previously described. To identify a molecular marker for the zebrafish
      PGCs, we cloned the zebrafish homologue of the Drosophila vasa gene, which, in
      the fly, encodes a germ-cell-specific protein. Northern blotting revealed that
      zebrafish vasa homologue (vas) transcript is present in embryos just after
      fertilization, and hence it is probably maternally supplied. Using whole-mount in
      situ hybridization, we investigated the expression pattern of vas RNA in
      zebrafish embryos from the 1-cell stage to 10 days of development. Here we
      present evidence that vas RNA is a germ-cell-specific marker, allowing a
      description of the zebrafish PGCs for the first time. Furthermore, vas transcript
      was detected in a novel pattern, localized to the cleavage planes in 2- and 4
      cell-stage embryos. During subsequent cleavages, the RNA is segregated as
      subcellular clumps to a small number of cells that may be the future germ cells.
      These results suggest new ways in which one might develop techniques for the
      genetic manipulation of zebrafish. Furthermore, they provide the basis for
      further studies on this novel RNA localization pattern and on germ-line
      development in general.

PMID- 9272957
TI  - Mothers against dpp participates in a DDP/TGF-beta responsive serine-threonine
      kinase signal transduction cascade.
AB  - Mothers against dpp (Mad) is the prototype of a family of genes required for
      signaling by TGF-beta related ligands. In Drosophila, Mad is specifically
      required in cells responding to Decapentaplegic (DPP) signals. We further specify
      the role of Mad in DPP-mediated signaling by utilizing tkvQ199D, an activated
      form of the DPP type I receptor serine-threonine kinase thick veins (tkv). In the
      embryonic midgut, tkvQ199D mimics DPP-mediated inductive interactions. Homozygous
      Mad mutations block signaling by tkvQ199D. Appropriate responses to signaling by
      tkvQ199D are restored by expression of MAD protein in DPP-target cells.
      Endogenous MAD is phosphorylated in a ligand-dependent manner in Drosophila cell
      culture. DPP overexpression in the embryonic midgut induces MAD nuclear
      accumulation; after withdrawal of the overexpressed DPP signal, MAD is detected
      only in the cytoplasm. However, in three different tissues and developmental
      stages actively responding to endogenous DPP, MAD protein is detected in the
      cytoplasm but not in the nucleus. From these observations, we discuss possible
      roles for MAD in a DPP-dependent serine-threonine kinase signal transduction
      cascade integral to the proper interpretation of DPP signals.

PMID- 9272958
TI  - Concentration-dependent patterning of the Xenopus ectoderm by BMP4 and its signal
      transducer Smad1.
AB  - Morphogens are thought to establish pattern in early embryos by specifying
      several cell fates along a gradient of concentration; a well-studied example is
      the Drosophila protein decapentaplegic (DPP) acting in the wing disc. Recent work
      has established that bone morphogenetic protein 4 (BMP4), the vertebrate
      homologue of DPP, controls the fundamental choice between neural and epidermal
      fates in the vertebrate ectoderm, under the control of antagonists secreted by
      the organizer region of the mesoderm. We now show that BMP4 can act as a
      morphogen, evoking distinct responses in Xenopus ectodermal cells at high and low
      concentrations, in a pattern consistent with the positions of the corresponding
      cell types in the embryo. Moreover, this complex cellular response to
      extracellular BMP4 concentration does not require subsequent cell-cell
      communication and is thus direct, as required of a classical morphogen. We also
      show that the same series of cell types--epidermis, cement gland and neural
      tissue--can be produced by progressively inhibiting endogenous BMP signaling with
      specific antagonists, including the organizer factor noggin. Finally, expression
      of increasing doses of the signal transduction molecule Smad1 accurately
      reproduces the response to BMP4 protein. Since Smads have been shown to act in
      the nucleus, this finding implies a direct translation of extracellular morphogen
      concentration into transcription factor activity. We propose that a graded
      distribution of BMP activity controls the specification of several cell types in
      the gastrula ectoderm and that this extracellular gradient acts by establishing
      an intracellular and then nuclear gradient of Smad activity.

PMID- 9272959
TI  - Developmentally regulated activation of apoptosis early in Xenopus gastrulation
      results in cyclin A degradation during interphase of the cell cycle.
AB  - Previous work identified a developmental timer that controls the stability of
      cyclin A protein in interphase-arrested Xenopus embryos. It was shown that
      cyclins A1 and A2 abruptly become unstable in hydroxyurea-treated embryos at the
      time that untreated embryos are beginning gastrulation (early gastrulation
      transition; EGT). We have demonstrated here that cyclins A1 and A2 are degraded
      at the equivalent of the EGT by the ICE-like caspases that are responsible for
      programmed cell death or apoptosis. Analysis of embryos treated with hydroxyurea
      or cycloheximide showed widespread cellular apoptosis coincident with cyclin A
      cleavage. Our data further indicate that the apoptotic pathway is present in
      Xenopus embryos prior to the EGT; however, it is maintained in an inactive state
      in early cleaving embryos by maternally encoded inhibitors. Characterization of
      the timing of the activation of apoptosis implicates the initiation of zygotic
      transcription at the mid-blastula transition (MBT) in the suppression of
      apoptosis in normal embryos. The decreased biosynthetic capacity of embryos
      treated with hydroxyurea or cycloheximide most likely interferes with the ability
      to maintain sufficient levels of apoptotic inhibitors and results in widespread
      apoptosis. Our results suggest a scenario whereby the apoptotic pathway is
      suppressed in the early cleaving embryo by maternally contributed inhibitors.
      Degradation at the EGT of maternal RNAs encoding these inhibitors is compensated
      for by new zygotic transcription beginning at the MBT. This indicates that the
      interval between the MBT and the EGT represents a critical developmental period
      during which the regulation of embryonic cellular processes is transferred from
      maternal to zygotic control.

PMID- 9272962
TI  - The Art of Anaerobes Conference. Athens, Georgia, USA, August 15-16, 1996.
      Abstracts.

PMID- 9272960
TI  - mago nashi mediates the posterior follicle cell-to-oocyte signal to organize axis
      formation in Drosophila.
AB  - Establishment of the anteroposterior and dorsoventral axes in the Drosophila egg
      chamber requires reciprocal signaling between the germ line and soma. Upon
      activation of the Drosophila EGF receptor in the posterior follicle cells, these
      cells signal back to the oocyte, resulting in a reorganization of the oocyte
      cytoplasm and anterodorsal migration of the oocyte nucleus. We demonstrate that
      the gene mago nashi (mago) encodes an evolutionarily conserved protein that must
      be localized within the posterior pole plasm for germ-plasm assembly and
      Caenorhabditis elegans mago is a functional homologue of Drosophila mago. In the
      absence of mago+ function during oogenesis, the anteroposterior and dorsoventral
      coordinates of the oocyte are not specified and the germ plasm fails to assemble.

PMID- 9272961
TI  - Antagonism between EGFR and Wingless signalling in the larval cuticle of
      Drosophila.
AB  - Signalling by the epidermal growth factor receptor (EGFR) plays a critical role
      in the segmental patterning of the ventral larval cuticle in Drosophila: by
      expressing a dominant-negative EGFR molecule or Spitz, an activating ligand of
      EGFR, we show that EGFR signalling specifies the anterior denticles in each
      segment of the larval abdomen. We provide evidence that these denticles derive
      from a segmental zone of embryonic cells in which EGFR signalling activity is
      maximal. Within each segment, there is a competition between the denticle fate
      specified by EGFR signalling and the naked cuticle fate specified by Wingless
      signalling. The final pattern of the denticle belts is the product of this
      antagonism between the two signalling pathways. Finally, we show that the
      segmental zones of high EGFR signalling activity depend on bithorax gene function
      and that they account for the main difference in shape between abdominal and
      thoracic denticle belts.

PMID- 9272963
TI  - Palliative care in South Australian nursing homes.
AB  - A survey of directors of nursing and registered nurses working in 151 South
      Australian nursing homes was conducted to identify the proportion of residents
      who received palliative care and the nursing implications of providing this care.
      The 71 (47%) responding directors of nursing reported that their homes had
      provided and/or were providing palliative care and that, at the time of the
      survey, approximately 10% of the residents were receiving palliative care. The
      registered nurses documented a range of specialized and time-consuming nursing
      procedures and care that were required by 89 recipients of palliative care. These
      residents were each receiving approximately 42 hours of nursing and personal care
      per week, but none were assessed as meeting the criteria for their nursing home
      to receive the maximum Resident Classification Instrument funding for 27 hours of
      nursing and personal care per week.

PMID- 9272964
TI  - RN's experiences of sex-based and sexual harassment--an empirical study.
AB  - A survey of 317 registered nurses enrolled in tertiary post-registration courses
      found that two thirds of the 197 respondents had encountered sexual harassment in
      the work place. A quarter of these nurses identified medical officers and 22.1%
      identified co-workers as their harassers.This paper identifies the harassing
      behaviours the respondents experienced, their responses to the behaviour and the
      effects the harassment had on them.

PMID- 9272965
TI  - A post-acute respiratory outreach service.
AB  - This paper describes an outreach nursing service for patients discharged from a
      Sydney hospital after treatment for an acute episode of chronic airflow
      limitation (CAL) and people referred for early exacerbation of the condition. In
      its first two years, 395 patients received the home-based service. The
      readmission rate of these patients within 28 days of discharge was approximately
      half that of the hospital's CAL patients in the year before the service was
      available. The cost of the outreach service in 1994-5 and 1995-6 was 36% and 61%
      lower respectively than the cost of hospitalizing the estimated 57 patients whose
      admission or readmission to hospital was avoided because their conditioned was
      managed at home by the outreach service.

PMID- 9272966
TI  - Digestion by fungal glycanases of arabinoxylans with different feruloylated side
      chains.
AB  - Alcohol-insoluble residues (AIRs) from Festuca and Zea cell cultures contained
      7.4 and 35 nmol esterified ferulate mg-1, respectively. Driselase solubilised 79%
      of the feruloylated material from both AIRs. Of the feruloyl esters solubilised
      from Festuca and Zea AIRs, 72 and 56% respectively were small enough to be mobile
      on paper chromatography. The major feruloylated product of Zea AIR was the known
      5-O-feruloyl-alpha-L-Araf-(1-->3)-beta-D-Xylp-(1-->4)- D-Xyl (Fer-Ara-Xyl-Xyl).
      In contrast, the smallest major feruloylated product of Festuca AIR was a
      feruloyl pentasaccharide (3) containing 3 Xyl, 1 Ara and 1 non-pentose residue
      (NPR). The Ara and two of the three Xyl groups of 3 were resistant to NaIO4. Mild
      acid hydrolysis of 3 gave xylobiose, a feruloyl trisaccharide and beta-D-Xylp-(1-
      >2)-(5-O-feruloyl)-L-Ara. Compound 3 was therefore NPR-(1-->3)-beta-D-Xylp-(1-
      >2)-(5-O-feruloyl)-alpha-L-Ar af-(1-->3)-beta-D-Xylp-(1-->4)-D-Xyl. We conclude
      that the complex feruloyl oligosaccharide side-chains of Festuca arabinoxylan do
      not protect the polysaccharide against hydrolysis by the fungal glycanases
      present in Driselase.

PMID- 9272967
TI  - Dictyophorines A and B, two stimulators of NGF-synthesis from the mushroom
      Dictyophora indusiata.
AB  - Two novel eudesmane-type sesquiterpenes, dictyophorines A and B, and a known
      compound, teucrenone, were isolated from the mushroom Dictyophora indusiata.
      Dictyophorines A and B promoted nerve growth factor (NGF)-synthesis by astroglial
      cells.

PMID- 9272968
TI  - Prenylated phenylpropenes from Coleonema pulchellum with antimicrobial activity.
AB  - The lipophilic root extract of Coleonema pulchellum was analysed and tested for
      antifungal and antibacterial activity. Eight previously undescribed prenyloxy and
      geranyloxy phenylpropenes, were isolated as major compounds together with the
      known evofolin-C as well as the lignans (+/-)-sesamin and (+/-)-prenylpiperitol,
      the diterpene (-)-pimara-9(11),15-dien-19-oic acid and the 2,4-decadienoic acid
      isobutylamide. All structures were established by spectroscopic evidence. From
      the new phenylpropenes, named evofolin-C-acetate, colenemol, colenemal, prenycol
      acetate, dehydroprenycol acetate, precolpuchol, colpuchol and colpuchol acetate,
      the dihydroxylated precolpuchol displayed the strongest antifungal and
      antibacterial activity against Cladosporium herbarum and Staphylococcus aureus,
      respectively.

PMID- 9272969
TI  - Terpenoids from Salvia glutinosa.
AB  - A new steroidal compound 1-oxo-7 alpha-hydroxysitosterol was isolated from the
      whole plant of Salvia glutinosa in addition to 11 known triterpenoids and three
      steroids. The structures were established by spectral data. Cytotoxic activity of
      the new compound and 7 alpha-hydroxysitosterol were tested against P-388 and KB
      systems; only marginal activity was found.

PMID- 9272970
TI  - Germin. Molecular cloning of cDNA that selects germin mRNA from bulk wheat mRNA.
AB  - (1) Bulk mRNA from germinated wheat embryos was denatured with methylmercury and
      subjected to electrophoresis in agarose gel to obtain a fraction of mRNA that was
      modestly enriched with respect to its complement of translatable germin mRNA.
      This fraction of mRNA was used as a source of primary templates for preparing a
      cDNA library. (2) Escherichia coli JM101 was transfected with recombinant pUC8
      plasmids containing cDNA inserts. Colonies of transformed bacteria (ca. 4 x
      10(3)) were differentially screened by hybridizing them with cDNA probes that
      were prepared from RNA populations containing different proportions of
      translatable germin mRNA. (3) A 160 base pair (bp) cDNA, which hybridized more
      strongly to the probe made from the RNA population containing the greater
      proportion of translatable germin mRNA in colony hybridizations, also hybridized
      more strongly to the RNA population containing the greater proportion of
      translatable germin mRNA when it was used as a probe for Northern analysis. (4)
      As judged by peptide mapping of a protein made by cell-free translation, the 160
      bp cDNA selected virtually pure germin mRNA from the bulk mRNA of germinated
      wheat embryos when it was used in "hybrid release" experiments. The same 160-bp
      cDNA was used to select a "full length" germin cDNA from a library prepared by
      the Gubler-Hoffman method.

PMID- 9272971
TI  - [Function and complications of diverse totally implantable systems for continuous
      intra-arterial infusion of FUdR in colorectal hepatic metastases].
AB  - Different totally implantable arterial infusion systems were compared in patients
      with liver metastases from colorectal cancer undergoing continuous intra-arterial
      infusion. Seventy-eight patients received continuous FUdR infusion using either
      totally implantable pumps (group a = 44 pts.) or ports fed by external portable
      pumps (group b = 34 pts.), and 57 patients received bolus infusion of Cisplatin
      (group c). Devices were cared for patency even after interruption of treatment,
      commonly caused by disease progression. Pocket problems most frequently occurred
      in group a (30%) compared to groups b (9%) and c (7%), whereas a higher incidence
      of catheter and infusion related problems was observed in group b (109%). System
      failure was recorded as a cause of interruption of treatment in two, 9, and 6
      cases in groups a to c, respectively. The 12-months patency rate was 92% in group
      a, 24% in group b (median 9 months), and 65% in group c (median 17 months).
      Though implantable ports allow adequate infusion periods in most cases they seem
      more adequate for bolus infusions.

PMID- 9272972
TI  - [Spontaneous bilio-digestive fistulas of lithiasis origin: our experience].
AB  - The Authors report their experience with spontaneous bilio-digestive fistulas of
      lithiasic origin. They examine the difficulties of diagnosis and treatment of
      this pathology also in consideration of probable complications, in particular the
      biliary ileus, in old patients often presenting metabolic or cardiopulmonary
      disorders, which contribute to worsen the prognosis.

PMID- 9272973
TI  - [Our experience with toracic outlet syndrome].
AB  - The Authors report their experience in 290 cases of thoracic outlet syndrome
      (TOS) and 71 cases of Paget-Schroetter syndrome, that is a condition due to
      thrombosis of the subclavian and/or axillary vein. They point out that diagnosis
      is mainly clinical-instrumental and the ulnar nerve conduction velocity (UNCV)
      test is of fundamental importance. The Authors emphasize how the good results
      obtained could be related to the complete removal of the first rib and to the
      axillary approach that they strongly support.

PMID- 9272974
TI  - [Carotid surgery and its monitoring in our experience].
AB  - Carotid endarterectomy (CEA) is the elective surgical procedure to prevent stroke
      due to stenosis of the carotid bifurcation. During a period of 17 years the
      Authors performed 215 operations on the carotid arteries of 168 patients. The
      average age was 64.6 and the male/female ratio was 3/1. Patients were symptomatic
      in 75.8% of cases and asymptomatic in the remaining 24.2%. Preoperative
      investigations consisted of echo-Duplex scanning, arteriography, cerebral CT or
      MRI. Indications for surgery were: stenosis wider than 70% in 173 cases,
      ulcerated or "high-risk" stenosis in symptomatic patients in 37 cases, and
      carotid malformation in 5 cases. The intraoperative use of shunt (12% of the
      operations) was selective, depending from the results of our monitoring system:
      stump pressure and transcranial Doppler (TCD) of the middle cerebral artery (MCA)
      ipsilateral to the procedure. The global major stroke/mortality rate was 3.3%
      (7/215), the minor morbidity was 8.8% (19/215). Mortality rate was 0.5% (1/215).
      The major stroke/mortality rate for symptomatic patients was 4.2% and for
      asymptomatic patients was 0%. The average follow up was 58 months (range 1-192)
      for 200/215 patients, with 15/215 patients (7%) lost. The postoperative incidence
      of stroke after 4 years was 8.5% (17/200), with an annual mortality rate of 1.6%
      (min. after 2 months, max. 118, average 55 months). CEA is a safe procedure to
      prevent cerebral infarctions, but it still carries an operative risk. A better
      monitoring would allow to understand the mechanisms of clamp-induced ischaemia
      and prevent it, therefore decreasing the operative risks and extending the
      surgical indications to a higher ratio of asymptomatic subjects. TCD is becoming
      essential for our goal: it is useful in deciding to insert an intraoperative
      shunt, check the carotid flow, recognize embolic events, and also during the
      initial phase of carotid preparation.

PMID- 9272975
TI  - [Hypochloremic metabolic alkalosis. A case report].

PMID- 9272976
TI  - [Recurrent biliary calculi].
AB  - The Authors report two cases of recurrent bile duct stones and discuss about the
      diagnosis and treatment of this infrequent disease. Although diagnostic and
      management procedures are similar to those commonly used in all types of biliary
      stones, therapeutical options may be different in relation to the different
      clinical pictures. The Authors strongly suggest that bilioenteric anastomosis and
      endoscopic sphincterotomy are the best procedures to assure a correct and
      definitive treatment of recurrent biliary stones. However, the adoption of
      different diagnostic and therapeutic approaches, rather than univocal schemes, is
      recommended.

PMID- 9272977
TI  - [Carcinoma of the splenic flexure. Nosological and therapeutic contribution].
AB  - Twenty-one patients undergoing colectomy for carcinoma of the splenic flexure
      from November 1996 throughout October 1993 were studied retrospectively. Clinical
      and prognostic features were compared with those of other colon cancers treated
      in the same period at the same Institution. No differences in symptoms at onset
      and stage distribution were found in the two groups. The complex removal of the
      cancer tissue was achieved with the resection of the major part of the transverse
      colon, splenic flexure, descending colon and its mesocolon. The splenic flexure
      cancer did not show a worse prognosis than other colon cancers.

PMID- 9272979
TI  - [Risk factors and breast carcinoma: our experience in a department of senology].
AB  - In relation to their experience, the Authors affirm that currently an early
      diagnosis of breast cancer, in an absolute preclinical stage, is obtainable by
      adequate screening using specific methods especially among women who are at
      greater risk. Primary prevention is not achievable at present; however some
      considerations based on protocols which provide a surgical prophylactic therapy
      in high risk breast pathologies and in very selected patients, are possible. In
      the light of these considerations secondary prevention has a predominant role and
      may be more effective and curative if the treatment is carried out in the
      earliest stages of the disease.

PMID- 9272978
TI  - [Sedation in endoscopic diagnosis: rationale of the use of specific
      benzodiazepine antagonists].
AB  - The aim of this study was to evaluate the best clinical use of Flumazenil, a
      specific antagonist of benzodiazepines, during endoscopic exams. Two-hundred
      patients were studied: 120 were treated with Flumazenil and 80 with placebo. The
      patients were prepared for the endoscopic exam with local anaesthesia and i.v.
      Diazepam administration. Controls performed at the end of the exam and at 5, 30,
      120 e 240 minutes from the administration of Flumazenil and placebo, allowed to
      evaluate the state of awakeness, the level of conscience and the capacity of time
      space orientation. Significantly statistical differences between the two groups
      were obtained at 5, 30 and 120 minutes after Flumazenil administration, while
      both groups had retrograde amnesia. The drug was well tolerated and there were no
      undesiderable side effects or reactions. The Authors therefore affirm that
      Flumazenil, in virtue of its competitive action toward benzodiazepine receptors,
      interrupts sedation with immediate awakening and improvement of the state of
      consciousness. Such drug, thus, permits the Day Hospital performance of
      endoscopic procedures which otherwise would require hospitalization, at the same
      time allowing the surgeon to use benzodiazepines at doses more adequate for
      surgical necessities.

PMID- 9272981
TI  - [Limitations of laparoscopic cholecystectomy].
AB  - Laparoscopic cholecystectomy has brought about an important and to some extent
      provocative revolution introducing the new dimension of minimally invasive
      surgery. The intrinsic limits of this new technique are analysed, as well as
      those that need to be established for its adoption to respect the rules of
      traditional surgery. Author's experience suggests that the explorative stage is
      widely indicated as a first step. This does not preclude early, reasoned and
      cautious conversion to laparotomy, but allows a safe and more generous use of the
      technique thanks to the possibility to check on patient selection.

PMID- 9272980
TI  - [Surgery of hyperthyroidism. Personal experience].
AB  - The Authors report their experience in the management of surgical
      hyperthyroidism, evaluating the different clinical pictures and the possibility
      of non surgical treatment. Advantages and disadvantages of both hemithyroidectomy
      and total thyroidectomy, are also described. The Authors conclude affirming their
      preference for techniques such as total hemithyroidectomy or thyroidectomy in
      some types of hyperthyroidism.

PMID- 9272982
TI  - [Sialolithiasis of the submandibular gland: therapeutic options and technical
      notes].
AB  - The Authors report their experience in the surgical treatment of submandibular
      sialolithiasis, particularly as far as simple sialolithotomy of Wharton's duct
      and submandibular gland resection are concerned. Care must be taken to minimize
      the risk of nerve damage (marginal mandibular branch of the facial nerve; lingual
      nerve; hypoglossal nerve).

PMID- 9272983
TI  - [Surgical approach to posthepatitic cirrhotic patient today].
AB  - A posthepatitic cirrhotic patient may undergo elective or urgent abdominal
      operation for an extra-hepatic or hepatic disease. According to the high
      postoperative morbidity (61%), surgery is indicated only for symptomatic or
      complicated cholelithiasis. A surgical procedure for refractory ascites has been
      devised to create a permanent peritoneo-venous shunt by a one way pressure
      sensitive valve (Leveen). The procedure is simple and brings a long lasting
      relief with recovery in strength and nutrition and improved kidney function.
      Sclerotherapy is widely used to treat acute variceal bleeding while repeated
      sclerotherapy is used in the long-term management to eradicate varices. When
      indicated, liver transplantation is the best treatment to prevent variceal
      bleeding recurrence. Also portosystemic shunts effectively prevent recurrent
      variceal bleeding. They are, however, major operations with an important
      morbidity and mortality, particularly in poor risk patients. The most advocated
      shunts today are the Warren distal splenorenal shunt and the Sarfeh portacaval
      shunt using a small diameter prosthetic H-graft. The transjugular intrahepatic
      portosystemic stent-shunt (TIPSS) is a new treatment for portal hypertension and
      its complications. From a haemodynamic point of view it allows balanced hepatic
      perfusion. Postoperative mortality is rare; further bleeding and encephalopathy
      are reasonably acceptable. The most relevant complications concern dislocation of
      the prosthesis, stenosis and thrombosis of the shunt, which can be corrected by
      non-invasive dilatation. Encephalopathy is the main complication of surgical
      portosystemic shunts. It is usually controlled by protein diet restriction, and
      administration of lactulose or oral antibiotics. In severe forms the patients may
      be treated by an oesophageal transection with oesophagogastric devascularization,
      and by a postoperative suppression of the portosystemic shunt using external
      maneuvers. Posthepatitic liver cirrhosis is frequently complicated by the onset
      of an hepatocellular carcinoma. Early detection (aFP, DCP, Echography) and
      curative resection are the best ways to improve long term prognosis.
      Segmentectomy achieves a good balance between liver function preservation and
      radical exeresis for tumours less than 5 cm in diameter. Liver transplantation
      may be considered for the treatment of long-staging cirrhotic patients in whom
      hepatocarcinoma development has been recognized at an early presymptomatic stage.
      Hepatic arterial chemoembolization (gelfoam, lipiodol, mitomycin C or
      doxorubicin) may improve the survival of patients with unresectable malignant
      disease of the liver. A marked reduction in liver size may occur in the weeks
      following an effective chemoembolization with objective (CT scan) and subjective
      improvement (amelioration of specific symptoms). Liver chemoembolization is
      absolutely contraindicated in the presence of jaundice disordered liver function
      (Child C) or complete portal venous obstruction. In the last years, the number of
      patients treated by liver transplantation has greatly increased. Surgical
      technique, postoperative management, and immunosuppressive therapy account for
      the dramatic improvement of the results. However, indications for selection of
      patients and the timing for liver transplantation are still not well defined.

PMID- 9272985
TI  - The merits of unrealistic scenarios.

PMID- 9272984
TI  - Rearrangements in the genomes of Vibrio cholerae strains belonging to different
      serovars and biovars.
AB  - The intron-encoded enzyme I-CeuI provides an excellent tool for rapidly examining
      the organization of genomes of related species of bacteria. Vibrio cholerae
      strains belonging to serovars O1 and O139 have 9 I-ceuI sites in their genomes,
      and V. cholerae strains belonging to serovars non-O1 and non-O139 have 10 I-ceuI
      sites in their genomes. This information can be used as a criterion to
      differentiate O1 strains from non-O1 and non-O139 strains. To our knowledge,
      intraspecies variation in the number of rrn operons has not been reported in any
      other organism. Our data revealed extensive restriction fragment length
      polymorphism based on a comparison of the I-ceuI digestion profiles of strains
      belonging to different serovars and biovars. From the analysis of partial
      digestion products, I-CeuI macrorestriction maps of several classical, El Tor,
      and O139 strains were constructed. While the linkage maps are conserved within
      biovars, linkage maps vary substantially between biovars.

PMID- 9272986
TI  - [BRACS--a method for cephalometric diagnosis and orthodontic treatment planning.
      Biometric radiographic analysis of the craniofacial skeleton].
AB  - The BRACS (the biometric radiographic analysis of the craniofacial skeleton) is a
      mathematically originated method for diagnosing malocclusion and planning
      orthodontic treatment. In the conventional cephalometrics, the measurements are
      to be made in an unstable reference frame without any definable direction or
      coordinate system. When using the BRACS, the natural reference structures can be
      replaced by an artificial stable reference system. The procedure is introduced in
      this paper.

PMID- 9272987
TI  - [The efficacy of dequalinium chloride/benzalkonium chloride as well as medicinal
      plants on the gingiva].
AB  - A comparative study involving 50 patients of both genders was conducted in order
      to determine the effect of dequalinium chloride/benzalconium chloride mouthrinse
      (Dequonal), and of a preparation of herbal essences (Parodontax) on gingival
      health. Each of the mouthrinses was used during four weeks by a group of 25
      patients who were instructed to abstain from any other oral hygiene measure
      during this period. Approximal plaque index, sulcus bleeding index and saliva pH
      were significantly enhanced by both preparations. A slightly better effect shown
      by dequalinium chloride/benzalconium chloride was not significant.

PMID- 9272988
TI  - [The problem of the reproducibility of occlusal contacts].
AB  - To perform target orientated therapy simulators of condyle movements (CPS) have
      been introduced recently. It is believed to improve analysis of jaw by computer
      aided registration and evaluation systems (i.e. transformation of the true axis
      and jaw movements for use in articulators). Although the electronic evaluation
      systems helped to improve our understanding of the movements of the jaw, up to
      now the reproduction of physiological and pathological movements and their
      therapeutic changes have not been solved satisfactorily. The reason is sometimes
      miscorrection of system inherent projection errors. Additionally, numerical
      analysis and changes of the registered pathological movements are restricted to
      certain limits within the articulators for therapeutical purpose.

PMID- 9272989
TI  - [Scanning electron microscopic studies on the corrosion behavior of
      osteosynthesis plates made of titanium and V4A steel. A case report].

PMID- 9272990
TI  - [Plaque and gingivitis reduction by an amine fluoride/stannous fluoride
      combination].
AB  - A clinical study on children has demonstrated that the accumulation of plaque and
      the development of experimental gingivitis can be reduced by a daily mouthrinse
      with AmF/SnF2. Low, reversible yellowish tooth staining can almost be prevented
      by mechanical oral hygiene. The efficacy of AmF/SnF2 was nearly the same as
      chlorhexidine and the F combination can be recommended for preventive plaque
      control, especially on high-risk patients.

PMID- 9272991
TI  - [Ultrasound in medicine].

PMID- 9272992
TI  - [Transcranial Doppler ultrasound--robotics-controlled transducers for quantifying
      the effect of acupuncture].
AB  - Transcranial Doppler Sonography (TCD) monitoring was carried out in 12 healthy
      subjects (mean age: 35.2 +/- 4.4 years; range: 26-41 years; 4 women, 8 men),
      prior to, during and following acupuncture. In all subjects an identical
      acupuncture scheme with a "general increase in Qi energy" setting was employed.
      Measurements were obtained with new robotic TCD probes enabling three-dimensional
      imaging of the middle cerebral artery by the use of the multi-scan technique. The
      results showed a significant (p < 0.01; ANOVA; Tukey test) increase in mean
      bloodflow velocity measured simultaneously at different depths within the right
      middle cerebral artery. Quantifiable changes in the physiological effects of
      acupuncture may contribute to improved acceptance of this unconventional
      complementary medical procedure.

PMID- 9272993
TI  - [Models for describing ultrasound scattering in blood].
AB  - The acoustic scattering properties of blood, which are of fundamental importance
      for the diagnostic utilization of ultrasonic signals backscattered by blood in
      Doppler-based procedures, have now been investigated using three different
      scattering models: the particle model, the continuum model and the hybrid model.
      The analysis shows the limitations of the approaches so far described in the
      literature, and also permits a modification of the hybrid model to produce an
      appreciably more accurate description of the true scattering properties of the
      blood. This is verified by a comparison of theoretical and experimental results
      obtained for a large range of haematocrits.

PMID- 9272994
TI  - [Value of ultrasound of the support and locomotor system--with special reference
      to radiation exposure and cost reduction].
AB  - In recent years, ultrasonic assessment of the locomotory system has become
      established both as a screening method in patients with chronic disorders and for
      evaluating acute injuries. Thanks to technical improvements to the equipment (use
      of high-frequency probes up to 20 MHz), ever smaller structures can be
      visualized. Ultrasonography can be carried out immediately following the clinical
      and possibly radiological-assessment, by one and the same investigator, and
      requires little extra time. A bilateral examination in particular permits good
      evaluation of the extent of an injury and, with appropriate experience and good
      quality equipment, an accurate assessment of the anatomical topography.
      Ultrasonography should now be used as the primary imaging method in the diagnosis
      of injuries to the following parts of the locomotory system, thus helping to
      minimize the number of expensive, and more invasive, diagnostic procedures:
      muscles and tendons, peri-articular soft tissue (in particular shoulder, knee and
      elbow joints), detection of intra-articular effusions, collections of fluid and,
      where applicable, ultrasonically guided puncture. In numerous other problems, too
      (postoperative complications, foreign bodies, fractures, osteomyelitis, soft
      tissue inflammation, etc.), ultrasound can deliver the first information. In this
      way, expensive diagnostic techniques can be reserved for special cases only, thus
      reducing costs. Furthermore, used as an adjunctive method, ultrasonography can
      reduce the number of diagnostic and follow-up X-rays in the case of injuries to
      the AC joint, shoulder dislocations, Hill-Sachs lesions, fractures in children,
      and for the detection of foreign bodies, again reducing radiation exposure and
      overall costs.

PMID- 9272995
TI  - [Ultrasound fracture diagnosis--an experimental study].
AB  - Thanks to the increasing use of ultrasonography in the diagnostic evaluation of
      the musculoskeletal system, and the development of high-resolution ultrasonic
      transducers with ever better image quality, as well as the greater general trend
      towards non-invasive techniques, the use of ultrasonography in the diagnosis and
      follow-up of fractures would appear to make good sense. The aim of the present
      experimental study was, therefore, to identify the typical acoustic pattern of
      fractures and areas of bone impression and defects, while taking account of
      possible sources of error due to artefacts. Experiments were carried out on
      cadaver bones immersed in a water bath, using 7.5 and 10 MHz linear transducers.
      Depending on its size, the bony defect is represented by an interruption of the
      cortical echo, or a dorsal band of echoes limited to the fracture zone. Of
      interest is the fact that fractures and bony defects are not represented as such
      when the transducer is directed parallel to the line of the fracture or the
      impression area. Particular attention needs to be paid to the numerous artefacts
      occurring at the margins of the fracture. In summary, it may be noted that using
      resolution transducers under standardised experimental examination conditions,
      cortical interruptions of not less than 1 mm can be identified.

PMID- 9272996
TI  - [The algorithm of imaging diagnostics of pulmonary embolism: is it time for a new
      definition?].
AB  - Acute pulmonary embolism (PE) is an increasing and underdiagnosed cause of
      mortality and morbidity in hospitalised patients: pulmonary hypertension based on
      chronic pulmonary embolism is an uncommon, but severe and surgically curable
      complication. Since clinical signs might be silent or unspecific, both acute and
      chronic PE require imaging methods for diagnosis and treatment planning. Chest
      radiographic findings are usually non-specific. Scintigraphy provides a high
      sensitivity for PE, but lacks anatomic resolution and sufficient specificity.
      Pulmonary angiography, albeit accurate, is an invasive procedure associated with
      low but still not negligible morbidity and mortality. Hence, non-invasive methods
      offer advantages. Spiral CT, for example, is most reliable in the diagnosis of
      acute and chronic PE: Such fast CT techniques provide a non-invasive means to
      detect and differentiate acute emboli and organised thrombi, as well as perfusion
      abnormalities and other concomitant findings. MRI offers both morphological and
      functional information on lung perfusion and right heart function, but its image
      quality still needs improvement to be comparable with CT. Thus, while MRI must
      still be tested in clinical studies. CT is recommended as a screening method in
      acute and chronic pulmonary embolism.

PMID- 9272997
TI  - [Effects of high-strip density anti-scatter grid on image quality and radiation
      dose].
AB  - PURPOSE: Using a new type of a stationary high strip density grid (13/75) for
      plain films of the abdomen, the effect was evaluated with regard to quality and
      patient dose in comparison with an established moving radiographic grid (12/40).
      METHODS: The high strip density grid (13/75) was compared with a 12/40 grid using
      test objects and 100 patients per each grid type for plain films of the abdomen.
      The examinations were carried out via the screen-film system, speed class (SC)
      400. Patients' weight, age and dose measurements were recorded. The image quality
      was evaluated via a multi-reader study using delineation of anatomical structures
      and a rating scale (score 1-5 or 1-3). RESULTS: Both measurements with test
      objects and patients abdominal plain films showed a decrease in radiation dose of
      17% using the 13/75 grid, and 24%, respectively. The delineation of 4 out of 7
      anatomical structures was slightly reduced with the new high strip density grid
      (maximum score reduction: 0.4), the image contrast, as well as the radiologists'
      subjective rating. CONCLUSION: Apart from an acceptable loss in image quality
      compared with the 12/40 grid, the new high strip density grid (13/ 75) enables a
      clear reduction in radiation dose.

PMID- 9272998
TI  - [Computerized tomography of the epiphyseal union of the medial clavicle: an
      auxiliary method of age determination during adolescence and the 3d decade of
      life?].
AB  - PURPOSE: To establish a reference population for the stages of epiphyseal union
      of the medical clavicle determined by CT. MATERIAL AND METHODS: Retrospectively,
      the thoracic CTs of patients under 30 years of age were reevaluated. Basic
      conditions were the lack of a bone development disorder and a sufficient
      assessment of the medial clavicle in a bone window setting. The stages of
      epiphyseal union were categorized as follows: Stage 1 refers to nonunion without
      ossification of the epiphysis, Stage 2 to nonunion with a separate and ossified
      epiphysis, Stage 3 to partial, and Stage 4 to complete union. RESULTS: Up to now,
      279 individuals could be included in the study. Stage 1 was observed till age 16,
      Stage 2 occurred from ages 13 through 22, Stage 3 was found from ages 16 through
      26. Stage 4 was first noted at age 22, and in 100% of the sample at age 27.
      CONCLUSIONS: CT is well suitable to determine the stages of epiphyseal union of
      the medial clavicle. It may become a generally accepted method of age
      identification during adolescence and the 3rd decade of life. The presented data
      serve as a reference population at least for white Europeans.

PMID- 9272999
TI  - [Detection of orbital foreign bodies by CT: are plain radiographs of foreign
      bodies still useful?].
AB  - PURPOSE: To prove the visualisation of orbital foreign bodies by CT. MATERIALS
      AND METHODS: In vitro we examined defined small objects of various materials
      (metal, wood, glass, stone) which are common as orbital foreign bodies, Density
      and minimum detectable size were studied. The findings of 27 patients with
      suspected orbital foreign bodies were compared with the results of plain
      radiographs, Comberg radiographs, sonography, and surgery. RESULTS: For iron, the
      minimum detectable size was 0.02 mm3. A differentiation of various materials by
      CT was not always possible, especially in small objects. There were wide
      differences in density of wood (-600 HU to +130 HU) according to hardness and
      water content. The CT scans correctly showed number and location of foreign
      bodies. Other methods were inferior in detection of foreign bodies. CONCLUSION:
      In diagnosis of foreign body injuries of the orbit, CT is the imaging method of
      choice.

PMID- 9273000
TI  - [Clinical relevance of CT of paranasal sinuses prior to bone marrow
      transplantation].
AB  - PURPOSE: To investigate the clinical necessity of CT of the paranasal sinuses
      before bone marrow or peripheral blood stem cell transplantation. PATIENTS AND
      METHODS: 80 patients with malignant disease underwent coronal CT of the paranasal
      sinuses prior to transplantation to exclude sinusitis. RESULTS: CT revealed
      sinusitis requesting therapy in 17/80 patients (21%). Patients with leukaemia and
      non-Hodgkin lymphoma were significantly more affected. Chronic sinusitis was
      found in two patients, mucosal swelling not requesting therapy in 22, and normal
      findings in 39. CONCLUSION: CT of the paranasal sinuses is advised in patients
      suffering haemoblastoses with an increased risk of infectious complications
      during the transplantation phase, because pathological findings can be expected
      in 21% of the patients. Diagnosis and therapy of an infectious focus within the
      paranasal sinuses is especially important prior to allogenous bone marrow
      transplantation.

PMID- 9273002
TI  - [Detectability of new medial infarcts by CT: appearance of ischemic signs].
AB  - PURPOSE: To evaluate the detectability of acute middle cerebral artery (MCA)
      infarctions by CT with regard to the time interval after symptom onset and to the
      infarction size. Analysis of the chronological appearance of signs of ischaemia.
      MATERIAL AND METHODS: Two examiners retrospectively and independently evaluated
      CT scans from 171 patients with acute MCA infarctions performed within 24 hours
      after onset of symptoms. RESULTS: 92, respectively 87% of the Infarctions were
      correctly diagnosed. The detection rate did not increase after the first hour
      after onset of symptoms. All MCA infarctions involving the lentiform nucleus, but
      only 83% of the infarctions covering < 33% of the MCA area, were recognised. The
      hyperdense middle cerebral artery sign (HMCA5) was present in 75% of the
      infarctions in the first 90 minutes and in 15% from hour 12 to 24. Hypodensity of
      the lentiform nucleus appeared within 150 minutes, hypodensity of the convexity
      cortex at the earliest 60 minutes after onset of symptoms. CONCLUSIONS: The
      detection rate of acute MCA infarctions corresponds with the infarction size, but
      does not significantly change after the first hour after symptom onset.

PMID- 9273001
TI  - [Value of dacryocystography in localization diagnosis of lacrimal duct stenosis].
AB  - PURPOSE: Evaluation of dacryocystography in the preoperative localisation of
      stenosis of the lacrimal passage. METHOD: The lacrimal system of 20 patients (25
      eyes) suffering from lacrimal passage obstruction was examined either by
      conventional (n = 20) or by digital (n = 5) technique. Diagnostic imaging was
      evaluated concerning topographic Information of the pathologic lacrimal system,
      localisation of the level and differential diagnosis of the cause of the
      obstruction. RESULTS: Cause of the obstruction was chronic dacryocystitis (n =
      16), dacryolithiasis (n = 1), atresia of the lacrimal duct (n = 2), posttraumatic
      lesions (n = 3), rhinosinusitis (n = 1) and carcinoma of the maxillary sinus (n =
      1). In 23 of 25 cases (92%) we found an exact correlation between
      dacryocystography and the intraoperative findings. The variation of stenosis
      types as well as different examination techniques are presented and compared with
      literature findings. CONCLUSION: Dacryocystography is a valuable method in the
      diagnosis and preoperative planing in lacrimal system obstruction.

PMID- 9273004
TI  - [MRI in testicular diagnosis: differentiation of seminoma, teratoma and
      inflammation using a statistical score].
AB  - PURPOSE: To differentiate scrotal pathology via MRI by means of a statistical
      score. METHODS: Between 1989 and 1995 MR images of 105 patients with scrotal
      pathology were rated retrospectively. In 69 cases linear discriminant analysis
      was used to differentiate seminoma, teratoma and inflammation. Six MRI attributes
      were found to be necessary and were weighted with a factor according to their
      importance. These factors were used to build a score. RESULTS: Criteria found to
      be important contained the distribution of the variate extensions of elements
      inside the pathological area and their maximal and minimal signal intensities.
      Furthermore, the contrast pattern of the pathological area and the visibility of
      healthy tissue in the pathological testicle was of importance. Seminoma was found
      to be homogeneous and well demarcated against healthy tissue. Teratoma was also
      well defined but characterised by inhomogeneous distribution of signal
      intensities. Inflammation showed diffuse signal increase of the pathological
      testicle, especially in T1-sequences. Using the score differentiation between
      tumors and inflammation succeeded in 94.2% between seminoma and teratoma in
      89.7%. CONCLUSIONS: Compared to other studies using visual MR image analysis
      differentiation of scrotal diseases was improved by using a statistical score.

PMID- 9273003
TI  - [Vascularization patterns in focal liver lesions: comparison of plain and signal
      enhanced amplitude-modulated color duplex ultrasonography].
AB  - PURPOSE: Morphology of focal liver lesions was studied by power Doppler. Plain
      images and images after i.v. application of galactose-based microbubbles
      (Levovist, Schering AG) were compared. METHODS: 21 patients with focal liver
      lesions were studied by power Doppler before and after application of the signal
      enhancer. RESULTS: In lesions that showed short pulsations in plain studies,
      vascular structures were visible after application of the signal enhancer. In
      hepatocellular carcinomas, multiple arteries with small diameter became visible.
      Peripheral veins were detected in metastases. A large feeding artery was detected
      in 1/2 haemangiomas with flow and in a focal nodular hyperplasia. CONCLUSION: In
      comparison to plain amplitude-modulated colour-coded duplex ultrasound, vascular
      patterns of focal liver lesions were more clearly visible after injection of a
      signal-enhancer.

PMID- 9273005
TI  - [The revised WHO classification of brain tumors. Radiological aspects of 4 new
      tumor entities].
AB  - PURPOSE: Characterisation of the classification of brain tumours authorized by
      the WHO. METHOD OF APPRAISAL: This classification was revised and published in
      its second version. In the revision, some tumours were regrouped histogenetically
      and some tumour variants were added. Radiologically relevant changes of the
      classification include the differentiation of four new tumour entities that are
      easily distinguished by MR imaging. These four tumours belong to the group of
      childhood tumours or tumours occurring in early adulthood and are characterized
      by a good prognosis after extirpation. RESULTS OF APPRAISAL: Central neurocytomas
      are small-cyst ventricular tumours associated with the foramen of Monroi and show
      moderate contrast enhancement. Infantile desmoplastic gangliogliomas/astrocytomas
      commonly consist of a solid tumour portion related to the leptomeninges with
      pronounced contrast enhancement and a typically very large cyst. Pleomorphic
      xanthoastrocytomas are circumscribed cortical tumours and usually show very
      moderate gyriform enhancement with only slight signs of a mass effect.
      Dysembryoblastic neuroepithelial tumours, which originate in the cortical/
      subcortical region, likewise show no mass effect; they are characterised by
      thickening of the cortex from surrounding dysplastic tissue and erosion of the
      calotte.

PMID- 9273006
TI  - [Results of CT-guided periradicular pain therapy].
AB  - PURPOSE: The effectiveness of CT-guided periradicular pain therapy was studied.
      MATERIAL AND METHOD: 55 patients with lumbar and/or radicular pain were treated
      by periradicular injections of 40 ml triamcinolon, in some cases combined with
      injection of the facets of the lumbar vertebrae. 36 patients had chronic
      symptoms; in 7, these were acute, and 12 patients complained of renewed disc
      symptoms following previous disc surgery. Approximately 4 months after the
      conclusion of treatment, the patients were requested to complete a questionnaire
      giving information on the course and after-effects of treatment. The
      questionnaire was repeated after 5 months. RESULTS: 55% of patients were free of
      symptoms or had had some improvement at the time of the questionnaire; 30%
      reported temporary improvement, and in 15% there was no change compared with the
      pre-treatment symptoms. At the time of the second questionnaire, the proportion
      of patients who had derived benefit from the treatment was somewhat lower, 49%
      reported that they were pain-free or improved, while temporary improvement was
      reported by 36% of patients. CONCLUSION: CT-guided periradicular pain therapy is
      a valuable procedure in patients in whom conservative measures prove ineffective,
      and when surgery is not indicated. However, only about half the treated patients
      maintain permanent improvement.

PMID- 9273007
TI  - [Comparison of radiological procedures in preoperative assessment of anchorage
      strength of spinal implants].
AB  - PURPOSE: To compare three techniques with regards to their ability to estimate
      pull out strength of spinal fusion hardware. MATERIAL AND METHODS: VDS-screw
      fixation strength in 50 human cadaveric vertebral bodies was approximated by
      means of pull out force measurement. Bone quality was assessed by Dual X-ray
      Absorptiometry (DXA). Quantitative Computed Tomography (QCT) and T2*-relaxation
      time. For each of these techniques, correlation with axial pull out force
      strength was investigated. RESULTS: Highest correlation was found for cancellous
      bone density measured by QCT (r = 0.72; p < 0.001). Immediately followed by DXA
      (r = 0.70; p < 0.001), which involves all bone components. Inverted T2*
      relaxation time (r = 0.55; p < 0.001) and cortical bone density (QCT) correlated
      just slightly with pull-out force strength. CONCLUSIONS: Absorptiometrical
      techniques like QCT and DXA are most appropriate to estimate VDS-screw fixation
      strength preoperatively.

PMID- 9273008
TI  - [Activation of blood coagulation and fibrinolysis after angiocardiography with
      ionic and non-ionic contrast media].
AB  - PURPOSE: To study the effects of a ionic (amidotrizoate) and a non-ionic x-ray
      contrast medium (iopromid) during routine levocardiography and coronary
      angiography, we employed assays that detect reaction products of thrombin and
      plasmin to assess the activation of the haemostatic system. METHODS: Subsequent
      to informed consent, 20 patients were randomly assigned to receive either
      amidotrizoate or iopromid during standard levocardiography and coronary
      angiography in a double-blind comparative study. Groups were comparable in
      respect of age, weight, sex and severity of the disease. No anticoagulation was
      provided. Coronary angiography was performed according to a standardised
      protocol. Consumption of contrast media and duration of the examination were
      comparable in both groups. RESULTS: Thrombin generation (F.1+2) and thrombin
      activity (TAT) were higher with the ionic contrast medium but did not attain
      statistical significance. Fibrin generation and degradation as expressed by D
      dimer fibrin split products was significantly increased in patients who had been
      receiving amidotrizoate (p < 0.05, U-Test). CONCLUSION: The non-ionic x-ray
      contrast medium induced significantly less haemostatic activation in vivo than
      did the ionic medium amidotrizoate. These data suggest that earlier in vitro
      observations of more pronounced anticoagulant effects of ionic x-ray contrast
      media are of limited significance for the evaluation of in vivo effects of x-ray
      contrast media on haemostatic function.

PMID- 9273009
TI  - [In vitro evaluation of the intravasal Doppler guide wire: determination of
      hemodynamic effects of stenoses in a flow model].
AB  - PURPOSE: In a pulsatile hydraulic model, haemodynamic changes caused by stenoses
      were assessed using an intravascular Doppler guide wire. MATERIAL AND METHODS: In
      defined stenoses (25, 50, 75 and 87.5% diameter ratio), and with and without
      collateral flow, a 0.018 inch (0.46 mm) 12 MHz Doppler guide wire was assessed.
      Flow velocity measurements were taken 20 mm proximal, in, and 20 mm distal to the
      stenoses. Average peak velocity (APV) and ratios of pre-/poststenotic velocities
      and pre-/intrastenotic velocities of APV were compared with the grade of
      stenosis. The degree of the stenosis calculated by the ratio of the cross
      sectional area, using the pre- and intrastenotic APV, was correlated with the
      actual stenosis. RESULTS: The intrastenotic APV increased significantly (APV
      proximal to the stenosis 15.15 +/- 4.5 cm/s, intrastenotic APV 134.8 +/- 130.9, p
      < 0.01, Wilcoxon-Mann-Whitney test). The difference between APV pre- and
      poststenotic was not significant (p > 0.5). Concerning the grade of stenosis the
      ratio APV pre-/intrastenotic and the consecutively calculated cross-sectional
      area stenoses was the best predictor (correlation with the known cross-sectional
      area stenosis r = 0.94 Pearson). CONCLUSION: Using the Doppler guide wire, APV
      measurements pre- and intrastenotic enable a reliable quantification of the grade
      of stenosis. The stenosis calculated via the cross-sectional area correlates
      significantly with the actual stenosis.

PMID- 9273010
TI  - [A new method in the determination of individual delay time in bolus application
      in spiral CT].
AB  - Helical-CT examinations, particularly CT angiography, require precise timing
      between the examination procedure and the individual dynamics of contrast medium
      distribution in the arteriovenous system of the patient. The necessary delay
      between contrast medium injection and onset of has usually been either estimated
      or determined by means of an additional helical CT examination. The present paper
      introduces a new technique which allows bolus analysis without an additional
      scan. Prior to a CT angiography with 10 patients, two techniques for bolus
      analysis (BA) were compared. Prior to diagnostic contrast medium enhanced
      examination, a native (BA I) and a dynamic (BA II) examination were performed.
      Ten seconds prior to the start of each examination, a 10 ml test bolus was
      applied with an injection flow rate of 3 ml/s. Both examinations lasted for 30 s.
      During BA I, increase in attenuation in the aorta was compared at different
      sites, during BA II consistently at the same site. Comparison of the individual
      peak times yielded a coefficient of correlation of r = 0.926. The median value
      for BA I was 18.4 +/- 5.4 s and 19.2 +/- 4.5 s for BA II. The difference between
      measurement of peak time was 1.2 +/- 1.16 s. This modified technique for bolus
      analysis during the primary native scan of the upper abdominal organs permits
      calculation of the required individual delay time between contrast medium
      application and scan start: no additional examination is required and the method
      can be performed with any helical CT unit.

PMID- 9273011
TI  - [Results and consequences of frequent quality control of quantitative clinical 1H
      MR-spectroscopy].
AB  - Different methods exist for an absolute quantification of in vivo proton MR
      spectra. According to the principle of reciprocity a simple method has been
      suggested previously, comprising the multiplication of the spectral signals with
      the unlocalised reference amplitude of the measurement as a correction for the
      different coil load. Afterwards, the result can be compared to measurements on
      phantoms in order to obtain in vivo metabolite concentrations. Thus, only one
      calibration would be sufficient in principle for all measured spectra. However,
      during a previous serial study on humans and phantoms we observed significant
      changes in transmitter amplitudes over time, although metabolite peak areas
      remained quite constant. Hence, the method led to incorrect metabolite
      concentrations. Since these effects are mostly underestimated or even neglected
      in clinical spectroscopy, the purpose of the present study was to investigate
      these instabilities over time in order to find a new correction method for
      quantitative MRS. According to this new method, the spectra corrected by the coil
      load have to be modified additionally by dividing by the reference amplitude of a
      phantom.

PMID- 9273012
TI  - [Inflammatory breast carcinoma versus puerperal mastitis. Difficulties in
      differentiation based on clinical, histological and MRI findings].

PMID- 9273013
TI  - [Fatal endocarditis as a complication of intra-arterial lysis therapy: a case
      report].

PMID- 9273014
TI  - [A rare case of cryoglobulinemia: radiological findings].

PMID- 9273015
TI  - [Thoracic manifestations of osteosarcoma].

PMID- 9273016
TI  - [Lipoblastoma in MRI].

PMID- 9273017
TI  - [CADASIL (Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy)].

PMID- 9273018
TI  - [Glass fragment in the corpus adiposum infrapatellare].

PMID- 9273019
TI  - [Osteoid osteoma].

PMID- 9273020
TI  - [Pneumocystis carinii pneumonia (PCP)].

PMID- 9273021
TI  - [Von Recklinghausen's neurofibromatosis].

PMID- 9273022
TI  - [Peritoneal splenosis].

PMID- 9273023
TI  - [Pseudoaneurysm of the right hepatic artery with an arterio-biliary fistula].

PMID- 9273024
TI  - [Atlanto-axial dislocation in os odontoideum].

PMID- 9273025
TI  - [Echinococcal cyst and uterus myomatosus].

PMID- 9273026
TI  - [EBV-associated primary T-cell non-Hodgkin's lymphoma during immunosuppression
      after lung transplantation].

PMID- 9273027
TI  - [Contact lenses. Infections and hygiene].
AB  - BACKGROUND: Contact lens wearers are subject to increased risk of infection, and
      an attempt was made to determine which factors cause the overproportional risk of
      infection? PATIENTS: The aim of this paper is to explain with appropriate
      bibliographic support why people who wear contact lenses are at risk of
      infection. RESULTS: The relative risk of keratitis is a function of the lens
      material and the wearing time of the contact lenses. Extended wear of hydrogel
      lenses is associated with an overproportional risk of infection. According to the
      literature, the frequency of complications in contact lens wearers generally is
      the result of poor hygiene in 66% of the cases. The general lack of hygiene among
      contact lens wearers must, therefore, be regarded as one cause among
      pathophysiological mechanisms of the eye. The microbial spectrum favors gram
      negative bacteria living in a wet environment such as Pseudomonas, Serratia and
      parasites like Acanthamoeba. CONCLUSION: The specific spectrum of pathogens and
      new problem organisms not only challenge the fitter but also the manufacturers to
      adapt hygiene (sanitary) measures and products to the new development. Disposable
      contact lens systems are the first step, but they do not solve all the problems
      of contact lens wearers. Therefore, the importance of contact lens hygiene must
      be especially emphasized when the ophthalmologist is giving instructions to the
      patient. On the other hand, hygiene should also not be neglected by the contact
      lens fitters since it is part of the whole problem.

PMID- 9273028
TI  - [Ophthalmia neonatorum caused by Chlamydia trachomatis. Rapid diagnosis and
      therapy].
AB  - BACKGROUND: In up to 73% of ophthalmia neonatorum, Chlamydia trachomatis is the
      causative agents. Untreated sequelae to the eyes and organs may be the result.
      The aim of this study was to determine the bacterial spectrum of ophthalmia
      neonatorum with special regard to chlamydia and their diagnostic tests. MATERIALS
      AND METHODS: We compared the results of 15 newborn with ophthalmia neonatorum.
      For the diagnosis we used a rapid diagnostic test, Immunofluorescent Antibody
      Staining and Culture on McCoy cells. Bacteria that were cultured on culture media
      were also identified. RESULTS: In 66% the newborn showed a positive rapid
      diagnostic test result that was confirmed by Immunofluorescent Antibody Staining.
      In 5 patients all tests were negative. CONCLUSIONS: In this study C. trachomatis
      was the most frequent pathogen. In the culture media we isolated mostly gram
      positive cocci but not Neisseria gonorrhoeae. We point out the value of an exact
      rapid diagnosis and specific treatment to avoid sequelae to the eye and organs.

PMID- 9273029
TI  - [Fornix reconstruction in ocular pemphigoid with Goretex surgical membrane].
AB  - After separation of symblepharons in ocular pemphigoid, transplantation of nasal
      or bucal mucosa is recommended to prevent recurrent lid fusion; however, it is
      not always successful. BACKGROUND: An 86-year-old patient was referred to our eye
      clinic because of trichiasis in ocular pemphigoid. In the right eye, the only
      functional eye, fusion of the lower lid and the globe was present. There was
      severe trichiasis with multiple lesions of the cornea and beginning
      neovascularization. The left eye showed complete fusion of the lid fissure and
      neovascularization of the cornea. To prevent the right eye from suffering the
      fate of the left, we tried to find a simple surgical method that could easily be
      performed on the multimorbid patient. METHOD: Under parabulbar anesthesia we
      separated the lower lid from the globe until free passive motility of the lower
      lid was achieved. A cut-to-size piece of Gore-Tex surgical membrane was prepared
      and fixated with resorbable u-sutures on the inner lid. The membrane was left in
      place for 4 weeks until suture lysis. A silicone tube, which was transitorily
      fixed to the outer lower lid, had an additional ectropionizing effect. Three
      months later, lower-lid ectropion surgery was performed, combined with tarsectomy
      to obtain a long-term effect. RESULT: Six months later the lower-lid fornix had
      stabilized, and the lid and globe had good motility. The corneal lesions had
      healed. CONCLUSION: The use of 0.1 mm membrane prevents penetration of cell
      because of the microstructure. Similar to the "bare sclera" technique, which is
      used in selected cases in strabismus or pterygium surgery, the inner lid and
      sclera were epithelialized separately from the remaining conjunctiva. The
      surgical membrane prevented recurrence of the symblepharon. We think the
      presented technique is an easy, quick method of preventing recurrence of lid
      fusion after separation of symblepharons.

PMID- 9273030
TI  - [Transcutaneous or transconjunctival peribulbar anesthesia?].
AB  - BACKGROUND: Transconjunctival peribulbar anesthesia is reported to permit better
      identification of the bulbar limits because of a better view into the fornix; it
      is also said to be less painful compared to transcutaneous peribulbar anesthesia.
      The aim of our study was to compare the two injection techniques. PATIENTS AND
      METHODS: This study comprised 46 patients undergoing eye operations under local
      anesthesia. They were allocated randomly in a prospective and simple masked
      study. Twenty-three patients received transconjunctival injections and 23
      patients transcutaneous peribulbar injections. Before injection, all patients
      received Oxybuprocain eyedrops for anesthesia of the conjunctiva. In all cases no
      separate injections for lid akinesia were performed. Before and 20 min after the
      injection, the following parameters were assessed: pain score (visual analog
      scale), frequency of conjunctival chemosis and the necessity for supplemental
      anesthesia. For identification of the bulbar limits we checked if it was possible
      to see the caudal and the cranial fornix. RESULTS: The transconjunctival
      injection was significantly (P = 0.05) more painful (5.6 +/- 2.4) than the
      transcutaneous injection (4.2 +/- 2.4). Among the patients with transconjunctival
      injection, in 66.6% the cranial fornix could not or was only poorly seen.
      CONCLUSIONS: Transconjunctival peribulbar anesthesia appears not to be more
      advantageous than transcutaneous peribulbar anesthesia.

PMID- 9273031
TI  - [Effect of diabetes mellitus on anterior central lens epithelium in cataract
      patients].
AB  - The relationship between diabetic metabolic disorder and the impairment of lens
      epithelium in the development of age-related cataract cannot be completely
      defined yet. In this prospective study, morphological criteria and the phosphorus
      content of the anterior central lens epithelium in type-II diabetics and
      nondiabetics are compared. PATIENTS AND METHODS: Fifty-six of the overall 159
      patients with age-related cataracts were suffering from type-II diabetes (group
      I) and 103 are nondiabetics (group II). In each case, a fragment of the anterior
      central lens epithelium was evaluated morphologically using a scanning electron
      microscope (S-2400) and examined by EDXA (X-ray spectrometer TN-5500), with
      regard to phosphorus content. The criteria considered were the degree of damage
      to the epithelium (score 1-3), the morphologically evaluated cell density and the
      "peak/background" relationship for phosphorus. RESULTS: The mean degree of damage
      to the epithelium was 1.48 +/- 0.53 in the type-II diabetic group (I) and 1.55 +/
      0.65 in the nondiabetic group (II), respectively. The median cell density of
      type-II diabetics (group I) was 4838 +/- 1033 cells/mm2 compared with 5454 +/-
      1368 cells/mm2 of the nondiabetics (group II). The mean "peak/background"
      relationship for phosphorus was 0.46 +/- 0.20 in group I and 0.51 +/- 0.26 in
      group II, respectively. CONCLUSION: In the younger patients, the significant
      decrease in cell density and the increased degree of damage to the anterior
      central lens epithelium in the type-II diabetic group could be attributed to the
      cataractogenic influence of diabetic metabolic disorder on the lens epithelium.
      Another possible indication for that was the smaller phosphorus content in this
      group as evidence of the decrease in the biological activity of the cells (ATP
      function). The primary cataractogenic importance of the lens epithelium in type
      II diabetics could not be concluded.

PMID- 9273032
TI  - [Early postoperative endothelial cell loss after corneoscleral tunnel incision
      and phacoemulsification in pseudoexfoliation syndrome].
AB  - INTRODUCTION: Corneal endothelial involvement can be found in pseudoexfoliation
      syndrome (PEX). Evaluation of possible differences in endothelial cell loss
      following cataract extraction was compared to normal eyes. PATIENTS AND METHODS:
      In a controlled clinical study we prospectively studied 20 patients with PEX and
      compared them with an age-matched control group with senile cataract. All
      patients were treated with a standardized self-sealing 7-mm corneoscleral tunnel
      incision, phacoemulsification and posterior intraocular lens implantation using
      sodium hyaluronate. In addition to a complete ophthalmological examination,
      quantitative and qualitative endothelial cell analysis of the central and
      peripheral cornea was performed preoperatively, at the first postoperative day
      and after 4 weeks using non-contact specular microscopy (Konan Noncon Robo-ca SP
      8000, Konan, Japan). RESULTS: In eyes with PEX (2394 +/- 271 cells/mm2)
      endothelial cell counts were 10.5% (P < 0.05) lower than in the control group
      (2674 + 341 cells/mm2). Intraoperatively, ultrasound time (90 +/- 51 s) and power
      (38 +/- 17%) did not differ between the two groups. After 4 weeks the mean
      endothelial cell loss in the two groups was 10.4% and 9.8%, respectively (P <
      0.001). The mean cell area increased by 55 and 48 microns2 (P < 0.001),
      respectively. Polymegethism increased postoperatively in both groups and
      stabilized at 4 weeks at preoperative values. Pleomorphism increased
      significantly only in the PEX group. CONCLUSIONS: In eyes with PEX no increased
      cell loss was found in the early postoperative period compared to normal eyes
      following corneoscleral tunnel incision and phacoemulsification. Due to
      preoperative reduced endothelial cell densities, endothelium-protecting measures
      are recommended in eyes with PEX.

PMID- 9273033
TI  - [Carcinoma-associated retinopathy in breast carcinoma and carcinoid tumor].
AB  - BACKGROUND: Carcinoma-associated retinopathy (CAR) is a rare paraneoplastic
      syndrome characterized by diffuse retinal photoreceptor degeneration in the
      presence of an epithelial tumor. We report on three patients, who developed
      paraneoplastic retinopathy in the presence of breast carcinoma and a cervical
      carcinoid tumor. MATERIALS AND METHODS: In addition to biomicroscopic,
      psychophysical, electrophysiological and angiographic examinations, serum samples
      were obtained for immunohistochemical staining of human retina. RESULTS: Ring
      shaped visual field defects with statokinetic dissociation and abnormal rod and
      cone responses were found. Immunohistochemical findings included reactions at the
      level of the inner segments of the photoreceptors, the outer nuclear layer and
      the outer plexiform layer in absence of anti-recoverin antibodies. CONCLUSIONS:
      CAR should be considered in the differential diagnosis of visual loss in presence
      of tumors other than small-cell carcinoma of the lung. The presence of
      antiretinal antibodies is compatible with a tumor-induced immune response to
      epitopes shared by both the tumor and retinal tissue. Apparently, various retinal
      proteins may function as autoantigens.

PMID- 9273034
TI  - [Confocal scanning laser indocyanine green angiography of classical choroid
      neovascularization].
AB  - "Classic" choroidal neovascularization (CNV) has a relatively uniform appearance
      in fluorescein angiography. In contrast, indocyanine green (ICG) angiography
      shows variable features of well-defined CNV. We examined 31 classic CNV patients
      secondary to age-related macular degeneration using a confocal laser scanning
      ophthalmoscope (Heidelberg Retina Angiograph) in order to determine ICG
      characteristics of classic CNV. Vascular patterns (97%), a hypofluorescent rim
      (84%), a hyperfluorescent margin (42%), late ICG leakage (32%) and "feeder
      vessels" were identified in variable frequency. Some of the ICG characteristics
      may correlate with histological features of the membrane and reflect
      proliferative activity. Extrafoveal "feeder vessels" may be amenable to laser
      photocoagulation in the presence of subfoveal CNV.

PMID- 9273035
TI  - [Simultaneous fluorescein and indocyanine green angiography with a confocal laser
      ophthalmoscope].
AB  - BACKGROUND: We report on our clinical experience with a recently developed
      confocal scanning laser ophthalmoscope for simultaneous fluorescein and
      indocyanine-green (ICG) angiography. MATERIALS AND METHODS: Following injection
      of fluorescein and ICG mixed in one syringe simultaneous confocal scanning laser
      fluorescein and ICG angiography were carried out using the Heidelberg Retina
      Angiograph (HRA). An argon laser (488 nm) and a diode laser beam (795 nm) from an
      external source were delivered via single-mode fibers. Emission was recorded
      between 500 and 650 nm and above 810 nm, respectively. Digital images were
      displayed simultaneously on a monitor during angiography. RESULTS: A total of 295
      simultaneous angiograms in 268 patients with various retinal and choroidal
      diseases, including exudative age-related macular degeneration with occult and
      classic choroidal neovascularization, were obtained. High-contrast images during
      all phases of the angiography were obtained. Besides mild side effects in similar
      frequency known from individual injections, no additional toxic or allergic
      reactions from simultaneous injections of the two dyes were observed.
      CONCLUSIONS: Confocal laser scanning angiography allows for simultaneous
      fluorescein and ICG angiography. Compared with consecutive investigations using
      both dyes, simultaneous angiography requires only one injection, and offers
      identical digital frames. Simultaneous injection is not associated with
      additional side effects.

PMID- 9273036
TI  - [Effect of locally applied lidocaine on expression of the oculocardiac reflex].
AB  - INTRODUCTION: The oculocardiac reflex causes severe bradycardic arrhythmias and
      is a frequent complication during surgical manipulation at the medial rectus
      muscle. The purpose of this study was to evaluate the influence of lidocaine
      administered topically on the muscle on the incidence of the oculocardiac reflex.
      PATIENTS AND METHODS: After obtaining informed consent, 140 patients with
      strabism or retinal surgery were included in this study. All patients received
      standard premedication and anesthesia and were randomly assigned to two groups.
      Patients (n = 70) randomly assigned to the first group received 1 mg/kg lidocaine
      applied topically to the muscle after opening the conjunctiva. Individuals in the
      placebo group received the same volume of saline (0.9%). Surgical stimulation
      occurred 5 min after administration of the drug. The study parameters (blood
      pressure/heart rate) were recorded before and after stimulation of the
      oculocardiac reflex caused by routine surgical preparation. RESULTS: Topical
      administration of lidocaine reduced the incidence of the oculocardiac reflex
      (86.1% vs 37.1%), and the frequency of severe bradycardiac arrhythmias was also
      significantly reduced (40 vs. 2.9%). Cardiac arrest for longer than 10 s did not
      occur in the lidocaine group. In the control group this phenomenon was observed
      in 14.8%.

PMID- 9273037
TI  - [Does the fundus perimetry determined edge of the blind spot depend on the
      superficial form of the papilla?].
AB  - BACKGROUND: We wanted to find out whether the borders of the blind spot depend on
      the surface topography of the optic disc and its surrounding area. PATIENTS AND
      METHODS: We therefore examined ten eyes with parapapillary atrophy adjacent to
      the temporal side of the disc. Fundus perimetry was performed under direct fundus
      control using a Rodenstock scanning laser ophthalmoscope. We examined the
      horizontal meridian of the optic discs in 0.5 degree steps using Goldmann IV
      stimuli with 10 different degrees of brightness and the Goldmann stimulus 1, 0 dB
      (greatest luminance). Six eyes with symmetric, "normal" excavation served as
      controls. Optic disc topography was measured with the Heidelberg Retina Tomograph
      (HRT). RESULTS: Stimuli with a large luminance power (Goldmann IV, 4 dB) were
      seen up to 0.8 degree centrally (i.e., towards the optic disc center) from the
      temporal edge of the parapapillary atrophy, but up to 1.9 degrees centrally from
      the nasal optic disc border (P < 0.01). Horizontal HRT section profiles of the
      optic disc consistently showed prominent nasal disc borders contrasting with a
      shallow excavation within the temporal parapapillary atrophy. In all six subjects
      with a normally shaped disc there was no such "nasotemporal asymmetry."
      CONCLUSIONS: The size of scotomas depends on the surface topography of the tested
      area. The prominent nasal part of the optic disc appears less "blind" than the
      shallow temporal part, probably due to more intensive light scattering by the
      prominent nasal part of the disc.

PMID- 9273038
TI  - [Unilateral parapapillary accumulation of sub- and intraretinal fluid. Double
      pitted optic papilla with parapapillary choroid neovascularization].

PMID- 9273040
TI  - [Cataract operation during therapy with anticoagulants. Principles, perioperative
      procedure, complications and recommendations].

PMID- 9273039
TI  - [Tissue-type plasminogen activator. An enzyme with multiple uses in
      ophthalmology].

PMID- 9273041
TI  - [The area of dentinal diffusion at the time of the manual preparation of root
      canals].
AB  - In this current piece of work we study the area of dentinal diffusion obtained
      with various irrigating agents which eliminate the smear layer: critic acid at
      concentrations of 10, 25 and 50%, 15% ethylene-diamino-tetraacetic acid (EDTA),
      and REDTA (compound of EDTA). All the agents proved their efficiency in
      eliminating the smear layer, which was corroborated by use of the sweep electron
      microscope and objectified using computerized image analysis, thus obtaining
      different diffusion areas with the various irrigating solutions used.

PMID- 9273042
TI  - [Mechanical instrumentation of the root canals. A study using SEM and
      computerized image analysis].
AB  - The effectiveness of ultrasonic and sonic instrumentation in eliminating the
      smear layer from instrumented root channels. The results were examined with
      S.E.M. and the effective areas of dental diffusion were calculated using the
      computerized image analyzer. The agents used: citric acid at concentrations of
      10, 25 and 50% as well as 15% EDTA, proved their efficiency with both types of
      mechanical instrumentation. However, the area of diffusion found was always
      greater using the ultrasonic instrumentation technique as opposed to the sonic
      instrumentation technique. 1, 2.5 and 5.25% sodium hypochlorite, as well as 10
      volume hydrogen peroxide were not effective in eliminating the smear layer using
      both types of instrumentation.

PMID- 9273043
TI  - [The determination of the intensity of premolar and molar maximal forces during
      the isometric contraction of the masticatory muscles due to forced mandibular
      closure].
AB  - The purpose of this study to quantify the activity of the masticatory muscles.
      For this we recorded the maximum bite force of opposing teeth during voluntary
      clenching. The study was carried out on 31 students aged 21 to 28 with a
      satisfactory dental arch. The measurements were obtained on one side only. Nine
      thickness of the traducers were used for the premolar zone and two for the molar
      zone. We determined an optimal thickness enabling the highest measurement: 6.5 mm
      for the premolars and 5.2 for the molars. The highest measurements were averaged
      and the following results were obtained: premolars-35 kgf for females and 50 kgf
      for males; molars 100 kgf for females and 130 kgf for males.

PMID- 9273044
TI  - [The demonstration of a relation between premolar force and molar force within
      the limits of a simplified approach to masticatory system functioning].
AB  - The purpose of this study is to show the existence of a correlation between the
      premolar and molar clenching forces obtained during a voluntary clenching
      exercise. The study concerned 32 volunteers aged 21 to 28 with no manducatory
      problems. The forces were obtained using a device with four Kiowa traducers
      arranged in a complete Wheatstone bridge. The analysis of the results obtained
      showed that there was a positive correlation between maximum molar and premolar.
      The analysis also shows that three results are a direct application of the theory
      of momentum. This enables us to propose a simple biophysical model to explain the
      functioning of the masticatory system.

PMID- 9273045
TI  - Extended abstracts of papers presented at the VIIth International Symposium on
      Luminescence Spectrometry in Biomedical Analysis. Detection Techniques in
      Chromatography and Capillary Electrophoresis. 17-19 April 1996.

PMID- 9273046
TI  - Web alert. Genetics of disease.

PMID- 9273048
TI  - [Longitudinal gradient of oxygen tension inside cerebral cortex capillaries].

PMID- 9273047
TI  - [Comparison of blast cell sensitivity to low-intensity laser radiation and
      chemotherapeutic drugs].

PMID- 9273049
TI  - [A higher level of integral animal behavior--expedient solution of a situational
      problem by the animal itself].

PMID- 9273050
TI  - [Growth and functional activity of the abdominal gland and marking behavior of
      Midday (Meriones meridianus) and Tamarisk (M. tamariscinus) gerbils].

PMID- 9273051
TI  - [Neurogenesis in Drosophila melanogaster hemizygotic, heterozygotic, and
      homozygotic notch mutants].

PMID- 9273053
TI  - [Molecular mechanisms of the pathogenetic disruption of phospholipid-chromatin
      interaction in the white rat brain in the case of unilateral
      gangliosympathectomy].

PMID- 9273052
TI  - [Genetic diversity of human immunodeficiency virus type 1 (HIV-1) in Russia].

PMID- 9273054
TI  - [Modification of muscle succinyl-coA-synthetase by diethylpyrocarbonate].

PMID- 9273055
TI  - [Mapping segments of the S1 nuclease hypersensitive sites in chromosome III of
      Saccharomyces cerevisiae].

PMID- 9273056
TI  - [Cytogenetic study of corneal cells from some rodent species from South Vietnam].

PMID- 9273057
TI  - [Change in the distribution of membrane organelles during formation of a single
      polykaryon cell center].

PMID- 9273058
TI  - [Nonmonotony of dose-effect dependence during irradiation of cells in vitro with
      pulsed laser radiation with a wavelength of 820 nm].

PMID- 9273059
TI  - [Phospholipase Cgamma1 and p66 protein in cell lines with an antiproliferative
      response to the epidermal growth factor].

PMID- 9273060
TI  - [Degradation of the ozone layer and heliotherapy].

PMID- 9273061
TI  - [Identification of the new protein kinase specifically transcribed in mouse
      tumors with high metastatic potential].

PMID- 9273062
TI  - [Maternal age and lifespan of the offspring].

PMID- 9273063
TI  - [Development of the adaptive response in human cells exposed to cadmium
      chloride].

PMID- 9273064
TI  - [Is an auto-injector useful in the treatment of erectile insufficiency using
      intracavernous injection?].
AB  - The technique and the fear of injection constitute a considerable cause for
      refusal, discontinuation and morbidity of the treatment of erectile insufficiency
      by intracavernous injection (ICI). The use of an automatic injection device has
      been proposed to minimize these problems. Despite a follow-up of 6 years, it is
      difficult to know whether the automatic injection device has had the same
      positive impact as in diabetic subjects. The use of this technique remains
      limited due to the lack of objective information concerning its possibilities.
      However, the rare reported series show that automation of ICI: a) improves the
      acceptability of self-administered ICI, b) lowers the discontinuation rate and
      morbidity. The automatic injection device can be proposed in any patient, after
      objectively informing him about the advantages and disadvantages. It is currently
      indicated: a) as first-line treatment in weak-hearted, anxious, clumsy subjects,
      or in patients with a physical handicap interfering with ICI or preferring
      automatic injection, b) secondarily, in the case of failure, difficulties or
      discontinuation because of technical problems.

PMID- 9273067
TI  - [Can primary kidney clear cell adenocarcinoma be differentiated from kidney
      metastasis with computed tomography?].
AB  - PURPOSE: To determine if CT scan provides morphologic criteria allowing
      differentiation between primary renal cell cancer of the clear type (PRCCCT) and
      renal metastasis (RM). MATERIALS AND METHODS: Twenty cases of PRCCCT and 20 cases
      of RM from various origins (excluding lymphomatous origin) were retrospectively
      analyzed by two independent readers. CT scans were evaluated with respect to
      tumor size, shape, location and number of tumors, encapsulation, contour
      sharpness, presence of calcification, and extrarenal involvement by tumor.
      RESULTS: A tumor size > 3 cm was more frequently seen in PRCCCT than in RM (100%
      vs 70% respectively, P < .05). Rounded shape was more frequent in PRCCCT than in
      RM (90% vs 50% respectively, P < .01). Encapsulation was more frequent in PRCCCT
      than in RM (70% vs 10%, P < .01, respectively). Calcification was depicted only
      in PRCCCT (35% vs 0%, P < .01). Enlarged perirenal lymph nodes were less frequent
      in PRCCCT than in RM (20% vs 55% respectively, P < 0.05). CONCLUSION: Results of
      our study show that a constellation of morphologic features suggest the diagnosis
      of PRCCCT rather than that of RM. Our study suggests that calcification is highly
      specific for the diagnosis of PRCCCT. However, percutaneous biopsy remains
      indicated to ascertain the diagnosis.

PMID- 9273065
TI  - [In vitro and in vivo models developed from human prostatic cancer].
AB  - The possibility of maintaining and studying human prostatic cancers in an in
      vitro and in vivo environment has allowed the development of rare but essential
      tools to study many aspects of the biology of these cancers. Although none of the
      available models is perfect, the sum of the studies conducted with these models
      over more than 20 years constitutes the basis for major progress in our
      understanding of this disease. The most widely used cell lines (cultured in
      vitro) are PC-3, DU-145 and LNCaP. They are limited by the fact that they are
      essentially androgen-independent cell lines, derived from metastatic sites. Due
      to the slow growth of prostatic cancers, it is very difficult to obtain cancer
      cell lines which can be transplanted in immunodeficient animals (such as athymic
      mice) and only a few xenografts are currently available, some of which, like PCV
      82, LuCaP 23, CWR-22, are androgen-dependent or sensitive. These models can be
      used to study host-tumour interactions as well as endocrinological interactions,
      stroma-tumour cell interactions, and to analyse molecular phenomena related to
      stages of hormone dependence and hormone resistance. In vitro and in vivo models
      of metastatic prostatic cancer have also been developed and appear to have a
      crucial impact on the understanding of metastatic mechanisms and new therapeutic
      approaches. This paper describes the main experimental models developed from
      human prostatic cancers, their main characteristics, their value compared to
      clinical cancers and some of the major studies conducted with these models. Due
      to the exponential progress in molecular biology techniques and oncogenetics, it
      appears essential to increase the number and diversity of experimental models of
      prostatic cancer in order to advance research concerning the crucial phenomena
      occurring during the course of this disease, from oncogenesis to currently
      incurable metastatic stages.

PMID- 9273066
TI  - [Treatment of advanced kidney cancer using recombinant erythropoietin].
AB  - OBJECTIVES: Study of the antitumour effects of erythropoietin on metastatic renal
      cell carcinoma. METHODS: After giving their informed consent, 20 patients with
      histologically proven metastatic renal cell carcinoma received subcutaneous
      recombinant erythropoietin three times a day at a dose of 150 IU/kg when
      haemoglobin was less than or equal to 12 g/dL or 75 IU/kg when haemoglobin was
      higher than 12 g/dL. Treatment was continued for a minimum of 8 weeks before
      reassessment and was continued thereafter, except in the case of progression or
      excessive toxicity. A staging assessment was performed every 8 weeks and the
      response was assessed on the basis of WHO criteria. A clinical and laboratory
      assessment was performed every two months to evaluate toxicity, graded according
      to the WHO scale. All but one of the patients had received immunotherapy or
      chemotherapy prior to inclusion in the study. RESULTS: One complete response (>
      12 months), one partial response (8 months), two minor responses, 10 cases of
      stabilisation and 6 cases of progression were observed. 15 patients received
      treatment at full doses. In 5 patients, the duration of treatment was reduced
      before the 8 weeks initially defined because of tumour progression in one patient
      and because of haemoglobin persistently greater than 15 g/dL in 4 other patients.
      Adverse effects consisted of 1 case of moderate headache, 2 cases of transient
      bone pain, and 1 case of transient hypertension. CONCLUSION: Erythropoietin
      exerts a moderate antitumour effect which needs to be confirmed by a phase II
      trial of first-line treatment in selected patients.

PMID- 9273068
TI  - [Treatment of ureteral stenosis using high pressure dilatation catheters].
AB  - INTRODUCTION: High-pressure dilatation catheters have been proposed as an
      alternative to open surgery in the treatment of ureteric strictures because of
      the low morbidity and short hospital stay. The objective of this study was to
      evaluate the results of this technique in patients with inflammatory ureteric
      strictures or uretero-ileal strictures. METHODS: From April 1991 to September
      1996, 25 strictures were treated by antegrade or retrograde dilatation with a
      high-pressure balloon catheter followed by stenting with a double J stent for an
      average of 2.1 months (1-5): 14 uretero-ileal strictures (tuberculosis,
      schistosomiasis, iatrogenic, radiotherapy). A good immediate result was defined
      as intraoperative rupture of the stricture under fluoroscopic control. A good
      long-term result was defined as absence of recurrence of the stricture, evaluated
      clinically and radiologically (IVU and/or ultrasonography). RESULTS: The good
      immediate result rate was 82% (19 out of 23 strictures, with 2 non-evaluable
      cases). One intraoperative complication was observed (double J stent advanced too
      for into the ureter). 22 strictures were evaluable after removal of the double J
      stent and the good long-term result rate was 64% with a mean follow-up of 8.5
      months (0.3-24). 8 patients developed a recurrence: 4 after Bricker, 3 with
      inflammatory strictures after radiotherapy and J with peritoneal carcinomatosis.
      CONCLUSION: This study shows that high-pressure balloon catheter dilatation of
      non-neoplastic ureteric strictures provides good results and can be considered to
      be the first-line treatment for these lesions.

PMID- 9273070
TI  - [The variability of the leakage pressure threshold due to exertion "the Valsalva
      Leak Point Pressure" as a function of the filling volume of the bladder].
AB  - OBJECTIVE: To determine the influence of the bladder filling volume on the
      Valsalva Leak Point Pressure (VLPP) in patients investigated for urinary stress
      incontinence. PATIENTS AND METHODS: 50 patients investigated for urinary stress
      incontinence were included in this prospective study. Evaluation consisted of
      clinical examination, urodynamic examination with simultaneous fluoroscopic
      assessment and cystoscopy. VLPP was measured while standing every 100 cc during
      filling until the cystomanometric bladder capacity. RESULTS: We observed a
      significant reduction of VLPP as a function of bladder filling volume. The VLPP
      measured at 200 cc constituted the reference value in view of its sensitivity and
      specificity for the diagnosis of type III urinary stress incontinence (Blaivas'
      classification). CONCLUSION: Measurement of VLPP must be standardized and
      interpreted as a function of bladder filling volume.

PMID- 9273069
TI  - [The Indiana pouch: a technic for simple continent urinary diversion].
AB  - OBJECTIVE: Description of the Indiana pouch, a continent urinary diversion after
      cystectomy for urogenital tumours, and for the sequelae of neurogenic and
      traumatic bladders. MATERIAL AND METHOD: This was a retrospective study of 16
      patients undergoing, between June 1991 and March 1995, cutaneous urinary
      diversion by ileocaecal graft, detubularized in the colonic segment, with
      continence ensured by the ileocaecal valve. The postoperative follow-up (4 to 36
      months) was performed at 3, 6 and 12 months (abdominal ultrasonography
      alternating with abdominopelvic CT scan), then annually (CT scan). Finally, a
      urodynamic assessment was performed in 7 patients. RESULTS: No early
      complications related to the reservoir were observed. Late complications of the
      diversion were related to the uretero-colonic anastomosis with 3 dilated renal
      subunits. Continence was achieved in 12 out of 15 patients, while one patient
      finally refused self-catheterization. In the patients in whom a urodynamic
      assessment was performed, the mean capacity of the reservoir was 671.4 +/- 273.9
      mL for a filling pressure of between 3.7 +/- 1.6 and 11 +/- 2.5 cm H2O and an
      ileocaecal valve closure pressure of 97.9 +/- 117.1 cm H2O (full reservoir).
      CONCLUSION: The Indiana pouch is a useful urinary diversion as it is simple to
      perform and is associated with a low revision rate, while ensuring low-pressure
      continence.

PMID- 9273071
TI  - [Isolated Burch type indirect colposuspension of the bladder neck in the
      treatment of stress urinary incontinence in women. Long-term results].
AB  - OBJECTIVES: Burch indirect colposuspension remains the reference surgical
      operation in the treatment of female urinary stress incontinence. The stability
      of the results is highly controversial and the causes of failure remain
      hypothetical. The objective of this study was to analyse the long-term results of
      this technique. METHODS: 100 women suffering from pure urinary stress
      incontinence, in whom a Burch indirect colposuspension was performed, were
      included in this study. These patients were reviewed with a mean follow-up of 5.2
      years and a questionnaire designed to assess the results was sent to their homes.
      RESULTS: 64% of patients no longer suffered from incontinence. Deterioration of
      the results was observed up to 5 years after the operation, but subsequently
      remained stable. The results were operator-independent. Low sphincter pressure (<
      30 cm H2O), preoperative detrusor instability, insufficient hormonal impregnation
      and a history of pelvic surgery were the main factors predictive of failure of
      this technique. CONCLUSION: This study confirms the benefit provided by this
      technique in almost two-thirds of patients and indicates the risk factors of
      failure which must be taken into account before proposing Burch indirect
      colposuspension to a woman suffering from urinary stress incontinence.

PMID- 9273072
TI  - [Medical treatment of venous priapism apropos of 46 cases: puncture,
      pharmacologic detumescence or penile cooling?].
AB  - OBJECTIVE: To analyse the efficacy of three nonspecific medical approaches to the
      first-line treatment of priapism : a) intracavernous injection (ICI) of alpha
      adrenergic agonists, b) cavernous puncture, c) penile cutaneous cooling. METHODS:
      46 cases of venous priapism, due to various aetiologies, were initially treated
      by ICI of alpha-adrenergic agonists (23 cases), puncture (14 cases) or cooling (9
      cases). These 3 methods were combined only in the case of failure and not
      uniformly, based on our experience. The results were analysed in terms of
      successful detumescence and preservation of erectile function. RESULTS:
      Detumescence was obtained and erectile function was preserved in almost 80% of
      cases, with conservative treatment alone. ICI (83%) and cooling (78%) were more
      effective as first-line treatment than puncture (57%). The delay to treatment was
      a more important parameter than the aetiology. Cooling was no longer effective
      after the 8th hour, puncture was no longer effective after the 9th hour and ICI
      was no longer effective after the 34th hour. Failures of conservative treatment
      and erectile sequelae were only observed in cases of priapism treated after the
      24th hour. CONCLUSION: The 3 methods have a similar degree of efficacy, provided
      they are performed early. Their indication depends on : 1) the duration of
      priapism, 2) the presence or absence of cavernosal anoxia. Schematically (and in
      parallel with aetiological treatment when possible) : a) in the case of painless
      priapism < 12 hours, cooling can be tried first, b) in the case of failure or
      painless priapism > 12, but < 24 hours, ICI of alpha-adrenergic agonists
      associated with puncture is indicated (except in the case of contraindications to
      ICI), c) in the case of painful priapism or > 24 hours, puncture must be the
      first treatment. In the case of failure, cavernosal blood gases should be
      performed to evaluate cavernosal anoxia and to guide management.

PMID- 9273073
TI  - [Volume and spatial representation of tumors in the core of the prostate gland].
AB  - OBJECTIVES: To describe a method of calculation of prostatic tumour volume
      allowing spatial representation of the tumour within the prostate gland. METHODS:
      60 radical prostatectomy specimens were studied. Each specimen was processed
      according to the Stanford technique, and each prostatic section was also divided
      into two parts, anterior and posterior, according to a sagittal plane through the
      urethra. 5 microns thick serial sections were performed every 3 mm. The tumour
      surface area was calculated under light microscopy on each slide. The tumour
      volume between two consecutive slides was considered to be the volume of a
      truncated cone. The overall volume obtained was then equal to the sum of these
      various partial volumes. Spatial representation was performed according to two
      axes for each of the anterior and posterior parts of the prostatic sections: x
      axis represented the prostate from the base to the apex, and the y-axis
      represented the tumour surface area in each prostatic section. RESULTS: The
      tumour volume ranged from 0.01 cm3, from 0.21 cm3 for pT2A to 1.98 cm3 for pT3C.
      pT3 tumours corresponded to the largest volumes, but some pT3 had a small volume.
      pT3 tumours were preferentially located close to Denonvilliers fascia : 40% of
      posterior tumours were pT3 versus 9% of anterior tumours (p = 0.01). CONCLUSION:
      The tumour volume on prostatectomy specimens can be evaluated by routine
      preparations and represents an additional element allowing better assessment of
      the TNM classification, as well as the predictive value of the information
      provided by prostatic biopsies.

PMID- 9273074
TI  - [The value of transrectal MRI in the staging of localized prostate cancer].
AB  - OBJECTIVE: To determine the diagnostic value of transrectal magnetic resonance
      imaging (MRI) in the local staging of prostatic cancer. METHOD: 75 patients
      suffering from clinically localized prostatic cancer were included consecutively
      from December 1992 to September 1996. An MRI examination (1.5 Tesla, Siemens)
      with a transrectal coil was performed before radical prostatectomy. The results
      of this examination in terms of capsular invasion, seminal vesicle lesion and
      apical invasion were correlated with the results of histological examination of
      the operative specimen and the findings of digital rectal examination,
      transrectal ultrasonography, serum PSA level and biopsy mapping. RESULTS: The
      best performance of transrectal MRI concerned elimination of seminal vesicle
      lesion with a specificity of 92%. The positive predictive value of transrectal
      MRI was 90% for the capsular invasion. The positive predictive value of
      transrectal MRI was 56% for the apex, the sensitivity was 40% and the specificity
      was 82%. When transrectal MRI did not reveal any extraprostatic involvement the
      risk of positive margins on radical prostatectomy was less than 6%. CONCLUSION:
      In this study, transrectal MRI appeared to be satisfactory to improve the staging
      of localized prostate cancer, especially in terms of seminal vesicle lesion and
      apical invasion, but, most importantly, appeared to be very useful to predict
      negative resection margins.

PMID- 9273075
TI  - [The incidence of the variability of the free PSA/total PSA ratio on the early
      diagnosis of prostate cancer].
AB  - INTRODUCTION: In patients with moderate elevation of total PSA, the use of the
      Free PSA/Total PSa ratio (F+T PSA) has been shown to be useful in the diagnosis
      of impalpable prostatic cancer. However, the cut-off values proposed in the
      literature vary from study to study and according to the immunoassay kit used.
      Our prospective study was designed to compare 3 different kits (Tandem, Cis Bio
      and Immunocorp) on the same series of patients in order to determine on the basis
      of these results and a review of the literature, the optimal ratio for which
      prostatic biopsies should be indicated in the presence of an isolated elevation
      of Total PSA. MATERIAL AND METHODS: Serum samples from 141 patients (43 cancers
      and 98 cases of histologically confirmed BPH) were included. Assays were
      performed concomitantly with histological examination of the prostate, using
      Tandem, Cis Bio and Immunocorp kits. RESULTS: In the overall patient population,
      Total PSA and Free PSA assays were statistically different for the 3 kits (p <
      0.001). The F/T PSA ratio was always statistically different between the cancer
      and benign prostatic hyperplasia groups (p < 0.002). The cut-off values defined
      by a sensitivity of 90% were of 0.22 for Tandem (specificity: 27.5%), 0.34 for
      Cis Bio (specificity: 19.4%) and 0.26 for Immunocorp (specificity: 26.5%). When
      the total PSA level was between 4.0 and 10.0 ng/ml, these cut-off values also
      differed: 0.23 for Tandem (specificity: 26.6%), 0.35 for Cis Bio (specificity:
      17.2%) and 0.25 for Immunocorp (specificity: 29.7%). In patients with a non
      suspicious digital rectal examination and a F/T PSA ratio less than 0.10, the
      cancer detection rate (number of biopsies required to diagnose 1 cancer) was 1.66
      for Tandem, 1 for Cis Bio and 1.87 for Immunocorp versus 7.7 while, when the F/T
      PSA ratio was greater than 0.22, the cancer detection rate was infinity (no
      cancer beyond this limit), 12.5 and 23, respectively. CONCLUSION: The F/T PSA
      ratio increases the specificity of prostatic cancer detection in patients with a
      total PSA between 4 and 10.0 ng/ml with a non-suspicious digital rectal
      examination, therefore resulting in a reduction of the useless biopsy rate and
      defining more relevant indications for biopsies in the case of periodic follow
      up. The systematic indication of this ratio in the screening context cannot be
      recommended, but it can be useful to demonstrate stage TIC tumours in order to
      avoid numerous useless biopsies.

PMID- 9273076
TI  - [Adenocarcinoma of the kidney associated with polycystic kidney treated by
      conservative surgery (apropos of a case)].
AB  - The authors report a case of renal cell carcinoma discovered incidentally in a 52
      year-old woman with hepatorenal and pancreatic polycystic disease. Treatment
      consisted of partial nephrectomy with no adjuvant therapy. After a 3-year follow
      up, the patient is still alive with normal renal function and no signs of
      recurrence. The pathogenesis and therapeutic modalities are discussed in the
      light of a review of the literature.

PMID- 9273077
TI  - [Emphysematous cystitis: apropos of 2 cases].
AB  - Emphysematous cystitis is a rare infectious disease of the lower urinary tract.
      Its reputedly serious prognosis is related to treatment failures revealing
      ignorance concerning its pathophysiological mechanisms. Two cases of this disease
      were seen in our department, both in diabetic men over the age of 70 years with a
      history of prostatism. They presented to the emergency department with complete
      urinary retention and alteration of the general state and fever. Urine culture
      isolated Klebsiella pneumoniae in both cases. Treatment consisted of bladder
      drainage associated with adapted antibiotic therapy and control of diabetes. A
      suprapubic prostatectomy was subsequently performed in one case and transurethral
      prostatic resection was performed in the other case. The prognosis of this
      disease depends on early diagnosis and rapid introduction of effective treatment.

PMID- 9273078
TI  - [The contribution of imagery in the early diagnosis of Fournier's gangrene].
AB  - Scrotal ultrasonography, completed by MRI, allowed the early diagnosis of a case
      of Fournier's gangrene, before the appearance of subcutaneous crepitation
      allowing rapid treatment adapted to the extent of necrosis. Ultrasonography is
      recommended in the assessment of inflammatory disease of the scrotum and/or
      perineum. MRI is able to refine the ultrasonographic data, and define the extent
      of gangrene as well as its starting point.

PMID- 9273079
TI  - [Evaluation of 20 years' experience of enuresis in children].
AB  - The clinical and urodynamic approach to enuretic children over a period of more
      than 20 years has allowed the authors to develop a multifactorial
      pathophysiological concept of this disorder. The main factors involved are
      psychological, familial, genetic, vesical, due to bladder immaturity, hormonal,
      due to a defect of nocturnal ADH secretion, hygiene and dietary habits, etc. The
      sleep factor is predominant in the majority of cases. Although nocturnal enuresis
      is apparently isolated in many cases, it is often associated with a state of
      bladder immaturity, sometimes latent during the day, but occurring at night with
      episodes of detrusor hyperactivity, occurring during various phases of sleep. In
      practice, the recognition, in children, of these factors, some of which require
      specific treatments, implies a management combining several of these therapeutic
      modalities.

PMID- 9273080
TI  - [Imaging of small renal tumors].
AB  - The increased incidence of detection of small renal tumours, less than or equal
      to 3 cm in diameter, is related to the generalization and improvement of
      radiological techniques. Many asymptomatic renal tumours are discovered by
      ultrasonography and computed tomography. Medical imaging is now able to identify
      simple cysts (morphological characters, absence of blood supply), angiomyolipomas
      (demonstration of the fatty contingent) and other solid renal tumours (tumour
      enhancement on computed tomography). Plain, followed by postcontrast CT looking
      for contrast enhancement of the lesions is the examination of choice in this
      context. MRI with Gadolinium injection looking for neoplastic enhancement can be
      useful in doubtful cases. Medical imaging is able to reliably demonstrate the
      vascular nature of solid lesions, but cannot distinguish between renal cancer,
      oncocytoma or another benign solid tumour. Medical imaging allows precise
      preoperative mapping when partial nephrectomy is envisaged.

PMID- 9273081
TI  - [The examination of sperm in the study of male fertility].
AB  - The laboratory investigation of male fertility is based on semen examinations and
      allows assessment of all events occurring between the onset of spermatogenesis
      and ejaculation. The sperm count and semen cytology remain the first-line
      examinations, but can be completed by more specific examinations allowing
      assessment of spermatozoan functions involved in passage along the female genital
      tract and penetration of the oocyte. However, apart from azoospermia, there is no
      absolute criterion beyond which semen can be considered to be infertile. The
      results must be interpreted by taking into account all these examinations which
      can provide element concerning the aetiology of infertility, helping to guide
      subsequent treatment. When the use of various in vivo treatments has failed,
      patients may require medically-assisted procreation (MAP) techniques. The type of
      MAP chosen will depend on the characteristics of the semen and the functional
      capacities of the spermatozoa.

PMID- 9273083
TI  - [Urethrolysis after surgical cure of stress urinary incontinence using colpopexy:
      surgical technics].
AB  - OBJECTIVE: Infravesical obstruction can occur after surgical cure for urinary
      stress incontinence (USI). Apart from palliative treatments with limited effects,
      this iatrogenic complication can be corrected by complete urethrolysis. The
      various indications and techniques of this surgery are presented. METHOD:
      Urethrolysis is designed to release the urethra and bladder neck and can be
      performed via a transvaginal or retropubic approach. Some authors then recommend
      resuspension of the bladder neck, while others use a Martius or omentum flap to
      reduce the risk of restenosis. RESULTS: The success of urethrolysis is measured
      by the return of normal micturition with complete disappearance of the irritating
      and/or obstructive symptoms. The success rate for the transvaginal procedure
      varies from 65% to 92% according to different teams, while the success rate via
      an abdominal incision was 93% in one series. CONCLUSION: Urethrolysis is a
      difficult surgical technique, whose long-term results have not yet been precisely
      determined. The transvaginal route is associated with a low morbidity and remains
      our personal preference to release the obstructed urethra after operation for
      USI.

PMID- 9273082
TI  - [Diagnosis of cancer of the prostate (I): Advancements in knowledge and practice
      since the consensus conference of 1989. The "Cancer of the Prostate" subcommittee
      of the Committee of Oncology of the French Association of Urology].
AB  - The prostatic cancer screening policy in France is defined by recommendations
      established at the 1989 consensus conference. Mass or individual screening by
      serum specific prostatic antigen (PSA) assay is not recommended. The Oncology
      Committee of the Association Francaise d'Urologie has up-dated the knowledge
      concerning prostatic cancer screening since 1989. The results are published in
      the form of a series of articles referring to the criteria used as prerequisites
      for cancer screening programmes. This article describes: 1) Current screening and
      treatment recommendations in France and in other countries. 2) The progress in
      our understanding of the prognosis, diagnosis and treatment of prostatic cancer,
      justifying revision of the screening policy. 3) The methodology and results of
      prospective screening studies and the projections of these results on the basis
      of the French population. Despite the 1989 recommendations, individual screening
      by serum PSA assay is widely performed both due to the characteristics of the
      test (simple blood test, low cost, high positive predictive value) and
      information of the public by the media concerning the morbidity and mortality
      related to prostatic cancer. The current data of the literature are unable to
      define the impact of PSA screening on the morbidity and mortality of prostatic
      cancer. Randomized prospective studies are currently underway. The absence of
      proof of a favourable impact of PSA screening is only one of the causes of the
      controversy concerning this screening technique, as another source of controversy
      is the magnitude of iatrogenic disorders induced by screening. In patients with
      raised PSA, the diagnostic examinations (biopsy) and curative treatments (surgery
      or radiotherapy) proposed are invasive, responsible for considerable morbidity
      and non-negligible mortality. Finally, the cost of screening remains unknown.
      Future recommendations must adapt their conclusions to changes in the current
      situation, in which prostatic cancer is simultaneously considered to be a non
      serious disease which does not justify screening and a serious disease, as soon
      as the diagnosis is made, justifying, for 95% of urologists, an invasive and
      mutilating treatment in men with a life expectancy of more than 10 years.

PMID- 9273084
TI  - [Spontaneous animal models for insulin-dependent diabetes (type 1 diabetes)].
AB  - Insulin dependent (type 1) diabetes in humans is a polygenic, auto-immune disease
      that is characterized, among other things, by the infiltration of the islets of
      Langerhans by immune cells (insulite) as well as many serum auto-antibodies
      (including islet cell antibodies: ICA). The medical goal is to diagnose the
      condition at a sub-clinical stage and then to prevent the disease from
      developing. Spontaneous diabetic rodent models, in particular the NOD mouse and
      BB rat are invaluable to the continuing progress of the work aimed at better
      understanding the human disease. In addition to these models, the study of type 1
      diabetes in larger animals, having a longer life-span would also be helpful. In
      dogs and cats, certain minor kinds of diabetes appear to be of type 1. The
      classification of diabetes types in carnivores remains poorly defined, however,
      epidemiological, genetic and metabolic studies are required before these diabetes
      can be used as operational models for the human pathology. Even if the
      classification of these diseases is clarified, the ethical and social
      considerations involved with the use of companion animals, will limit the use of
      these animals as models for spontaneous diabetes. The selection of a specific
      line of diabetic dogs should perhaps be considered.

PMID- 9273085
TI  - [Impact of the cellular concentration of milk in goats on its production and its
      composition].
AB  - Using records from the Milk Registration Organization for 254 dairy-goat farms
      located in western France, the economical impact of mammary gland inflammation on
      milk yield and composition was measured after 200 days of lactation. This
      assessment was performed in groups of goats belonging to the same farm and the
      same breed and having the same parity. Three levels of somatic cell count (SCC)
      were defined in order to discriminate goats on the basis of the intensity of
      inflammatory reaction of their udder: < 750,000 cells/mL (CCI1), between 750,000
      and 1,750,000 cells/mL (CCI2), > 1,750,000 cells/mL (CCI3). From 404 groups
      characterized by an average number of 12,4 CCI1 goats and 14,2 (CCI2 + CCI3)
      goats, the average milk yield of the goats whose SCC was superior to 750,000
      cells/mL was inferior to that of the CCI1 goats in 79.2% of the groups. In a sub
      sample of 366 groups, the average loss of milk production for the CCI2 goats
      compared to the CCI1 ones was 55 kg. In an other sub-sample of 41 groups, the
      milk production average loss of the CCI3 goats reached 132 kg. For all of the 404
      groups, (CCI2 + CCI3) goats had a lower fat content of 0.3 g/kg and in contrast a
      higher protein content of 0.6 g/kg. A second evaluation using a multidimensional
      variance analysis model in a population of 20796 goats showed the same results.

PMID- 9273087
TI  - [Fracture of the penis: description of a case].
AB  - Fracture of the penis is not a frequent event and it consists of a rupture of the
      tunica albuginea of the corpora cavernosa and sometimes of the urethra; the
      lesion occurs when the penis is erect because during erection the tunica
      albuginea is very thin and not flexible and it can be easily damaged by a trauma;
      most lesions occur during intercourse for impact of the erect penis against the
      female perineum or the pubic synphisis, but lesions during masturbation,
      fightings or falling off the bed are also described [1-2-3]. Clinically there are
      pain, detumescence, hematoma and recurvatum of the penis toward the opposite side
      of the lesion and hematuria if also the urethra is damaged. Usually diagnosis is
      quite easy with a good anamnesis, clinical examination and echotomography which
      can reveal presence of hematoma and hypoechogenic areas along the tunica
      albuginea or the urethra that appears irregular. Nowadays, fractures of the penis
      need a surgical approach to obtain good results avoiding consequences such as
      recurvatum or fibrotic areas [3-4-7-8]. We describe two cases of fracture of the
      penis occurred in two young men during masturbation and treated surgically with
      excellent results: twelve and eighteen months respectively after surgery patients
      are well and can enjoy a normal sexual activity with no problems at all.

PMID- 9273086
TI  - [Complicated urachal cyst: a difficult differential diagnosis].
AB  - Embryologically, the allantois connects the urogenital sinus with the navel.
      Normally, the allantois is oblitered before the birth and is represented by a
      fibrous cord, called urachus, extending from the dome of the bladder to the
      navel. Urachal formation is directly related to bladder descent. Incomplete
      obliteration sometimes occurs. Disease rarely occurs in urachus, but
      adenocarcinoma is the most fearful and rare, and it represents the 0.01% of the
      whole adult carcinoma, the 0.17-0.34% of the whole bladder malignancy, and the 20
      30% of the bladder adenocarcinoma. Yet urachus may be seat of other kinds of
      benign pathologies characterized by incomplete obliteration of its lumen. Only if
      the ends of the urachus seal off, a cyst of that body may form and may become
      quite large, presenting a low midline abdomen mass. Adenocarcinoma may occur in a
      urachal cyst, particularly at its vescical extremity. Cystis usually have an
      asymtomatic course. Occasionally these cystis can be discovered during
      sonographic examination. If the cyst becomes infected, signs of general and local
      sepsis will develop, sometimes involving the peritoneum. Sometimes, in these
      cases, it is difficult to diagnose the presence of an adenocarcinoma and,
      particularly, its cystic variant. By using the common diagnostic instrumental
      device, we cannot reach a certain diagnosis, essential to perform a correct
      medical or surgical treatment. The case reported concerns a twenty-five years old
      man, over and over again examined, complaining of ipo-mesogastric abdominal pain,
      mild fever, increment of flogosis index and transaminasis, microscopic hematuria
      and urinal discomfort. Sonographic suprapubic examination, performed during
      urological consultation, showed an urachal neoplasm. Cystoscopy and TC evaluation
      didn't permit a certain preoperative diagnosis. A surgical explorative operation
      was performed and the neoplasm, a part of a bladder dome, omental flap and a part
      of rectus muscles, were removed. In order to reconstruct the abdominal wall we
      used a large Polypropilene patch. The hystological report outlined a large
      urachal cyst, a flogosis and a purulent necrosis invading the surrounding tissue
      and the peritoneum. The patient was discharged after twenty-five days and he had
      a good functional performance. In the light of the reported case, the surgical
      treatment seems to be the best solution before the onset of complications that
      should expose patients to difficult and demolitive surgical operations and that
      should protract the hospitalization.

PMID- 9273088
TI  - [Screening for prostatic carcinoma in dysuric patients: diagnostic protocols and
      cost-benefit analysis].
AB  - This work deals with our experience of a programme of early diagnosis of prostate
      cancer carried out on patients suffering from dysuria through rectal-digital
      examination (EDR), hematic dosage of PSA (IRMA COAT-A-COUNT DPC) and transrectal
      echtomography. We have also quantified the costs and verified which methods,
      either single or combined with other methods, are most advantageous as regards
      costs/benefits. From Jan 1991 to Jan 1995 306 of 1185 patients (25.8%) underwent
      prostate biopsy by means of transperineal echograph with gauge 18 needles as in
      Hodge's technique. Histologic examination revealed prostate adenocarcinoma in 81
      (26.5%) cases, benign prostate hypertrophy in 196 (64%), acute and/or chronic
      phlogosis in 26 (8.5%) and granulomatosic prostatitis in 3 (1%). The diagnostic
      sensitivity, preciseness and accuracy were, respectively, 92.5%, 78.3%, 79.3% for
      the EDR, 80.2%, 93.3% and 90% for PSA with cut-off 10 ng/ml, 91% 78.3%, and 90%
      for the PSA with cut-off 4 ng/ml, 100%, 30.3% and 48.6% for the echograph, 98.8%,
      60% and 77% for EDR+PSA (cut-off 4 ng/ml), 98.8%, 65.8 and 79.9% for EDR+PSA (cut
      off 10 ng/ml), 100%, 22% and 64.2% for EDR+echograph, 100%, 20% and 62.9% for
      echograph+PSA (cut-off 4 ng/ml), 100%, 26.6% and 64.9% for echograph+PSA (cut-off
      10 ng/ml). We calculated that a programme of early diagnosis using the three
      methods, if completely at the patient's expense, would cost 207.000-437.000 lire
      (average 322.000) per patient for a total of 245,295,000-517,845,000 (average
      381,570,000). An eco-guided prostate biopsy with a histologic examination would
      cost 250.000-500.000 lire (average 375.000) per patient with a total cost for 306
      patients of 76,500,000-153,000,000 (average 114,750,000). We also quantified, in
      the light of the results reported here, the number of biopsied which would have
      been necessary if we had used only two methods in the screening and we also
      estimated the costs. The results reveal that the echograph is not to be
      considered as a first approach method as it gives a high number of false positive
      results; in fact if we had excluded it from the screening we would not have
      ignored any diagnosis of prostate neoplasia and we would have avoided about 141
      (46.2%) biopsied with a reduction in health expenditure of 62.1%. On the contrary
      the EDR and the PSA have a better cost/benefit result: setting the cut-off of the
      PSA at 4 ng/ml or at 10 ng/ml without varying the diagnostic accuracy, the
      sensitivity and/or specificity of the method increase respectively. To conclude,
      we consider the EDR and the serum dosage of PSA necessary and adequate methods in
      the programme of early diagnosis and screening of prostate neoplasy. The prostate
      echography should be reserved for cases of doubt (hematic PSA between 4-10 ng/ml
      etc.) and for the exclusion of needle biopsy. These measures also result in an
      optimization of health expenditure.

PMID- 9273089
TI  - [Renal lymphoma: an atypical mass in search of characterization].
AB  - We report the case of a B cell, renal non-Hodgkin lymphoma come to our attention
      due to urologic symptoms. A review of the literature is provided and it is
      discussed the differential diagnosis with renal cell carcinoma.

PMID- 9273090
TI  - [Immunotherapy for metastatic renal carcinoma with interleukin-2 in a subcutanous
      administration schedule of short duration. Subcutaneous IL-2 in renal carcinoma].
AB  - It has been shown that low-dose subcutaneous (SC)IL-2 exerts an efficacy similar
      to that described for the intravenous high-doses in the immunotherapy of
      metastatic renal cell cancer (RCC). However, it remains to be established which
      could be the optimal duration of treatment. The most common schedules with
      subcutaneous IL-2 are generally consisting of 6 weeks of therapy, with an IL-2
      dose of about 6 million IU/day. This study was performed to evaluate the efficacy
      of IL-2 subcutaneous immunotherapy with a duration of 4 weeks only. The study
      included 13 evaluable metastatic RCC patients. IL-2 has been injected
      subcutaneously at 6 million IU/day for 6 days/week for 4 weeks, by repeating a
      second cycle in nonprogressing patients after a 21-day rest period. Objective
      tumor regressions were achieved in 3/13 (23%) patients consisting of CR in 1 and
      PR in the other 2. Stable disease was obtained in other 6 patients. This
      preliminary study would suggest that a shorter dose-matched S.C.IL-2
      immunotherapy may have a similar therapeutic efficacy in metastatic RCC.
      Therefore, the 4-week IL-2 S.C. immunotherapy, instead of the 6-week schedule
      could become the standard immunotherapeutic schedule, with following decreased
      cost and toxicity.

PMID- 9273091
TI  - [The negative effect in patients with varicocele of coincidental didymo
      epididymal morpho-pathology on sperm response before and after surgical
      correction].
AB  - In order to assess the relative incidence of varicocele (V) alone and V+
      coincidental didymo-epididymal morphological abnormalities (DEMA) and the role of
      these pathologies on the pre- and post-surgical sperm outcome, 151 selected
      (previous exclusion of cases with bilateral V, seminal infections, antisperm
      autoAb) patients (aged 20-41 yrs) affected by left V at Doppler ultrasonography,
      underwent both ultrasound scrotal content examinations and semen analyses (sperm
      density, total sperm count, forward motility and normal morphology employing as
      frequency distribution) before and after varicocelectomy (on months 4-8-12,
      taking for statistical comparison the maximal post-surgical sperm value
      registered vs. mean correspective pre-treatment value). One-hundred two (67.5%)
      patients exhibited V alone (group A), whilst 49 (32.5%) patients showed V+DEMA
      (group B). As regards V, DEMA lesions (testis size < 12 ml; epididymides
      abnormalities: increased head (> 11 mm) and/or tail (> 6 mm) diameter, multiple
      microcysts; large idrocele) were omolaterally in 21/49 (42.8%) eterolaterally in
      11/49 (22.5%) or bilaterally in 17/49 (34.7%). An additional group of 25
      patients, exhibiting the above ultrasonic DEMA lesions alone without V, served as
      controls (group C) for semen statistical analysis in the pre-surgical period
      only. In this phase among groups A vs B, A vs C, B vs C, frequency distributions
      of all sperm parameters studied (excepted for density not significative only
      between B and C group patients) were significantly different. The following data
      were registered from A, B and C patient groups respectively: a) azoospermia was
      present in 12.7%, 34.8% and 24%; b) oligozoospermia (< 20 mil/ml) in 39.2%, 49%
      and 48%; c) normozoospermia in 48.1%, 16.3% and 8%; d) total sperm count was < 40
      millions/ejaculate in 44.1%, 91.9% and 76%; e) asthenozoospermia (forward
      motility < 25%) was present in 32.3%, 71.4% e 72%; f) teratozoospermia (oval form
      <30%) was present in 34.3%, 62.3% and 48%. In the post-surgical follow-up
      examinations, significative changes with ameliorated frequency distributions of
      all semen parameters were observed within group A only, while these same
      parameters remained unmodified within group B patients, thus being together a
      significative difference between groups A vs B higher than that observed in the
      pretreatment. The coexistence of DEMA+V seems to determine two important effects
      on sperm output: a) in the pre-treatment, this selection judgement allowed to
      distinguish a different frequency distribution of semen parameters between
      patients affected by V alone and V+DEMA; b) since patients with V alone in
      comparison with V+DEMA patients groups had a favourable sperm outcome, the
      assessment of DEMA in patients with V seems to be mandatory for a better sperm
      prognostic judice.

PMID- 9273092
TI  - [Echodynamics of the cervical ureter junction].
AB  - Transrectal dynamic ultrasonography is a 3 dimensional study that identifies
      accurately bladder neck (B.N.) diseases during micturition, providing precise
      noninvasive images of the B.N. orifice and the posterior urethra. This technique
      requires a 7-10 Mhz high frequency linear transducer. Benign Prostaic Hyperplasia
      (BPH) may restrict the urethral lumen and deviate its intra prostate tract. The
      images obtained allow a detailed and precise analysis of the B.N. and
      intravesical development of the median lobe. The urethra classically has a
      stretched and elongated appearance. This technique is useful in the diagnosis and
      in the follow up of neuropathic bladder. It is also useful in morphological and
      dynamic study of the B.N. after TURP. Diagnosis of B.N. hypertrophy or sclerosis
      is easy if a posterior beak at internal meatus level and positive stop test are
      present. After radical prostatectomy or radical cystectomy with orthotopic
      neobladder, this technique is useful to evaluate the internal urethral meatus and
      voluntary skeletal sphincter providing to a continence mechanism. We believe
      dynamic transrectal echography should become a procedure to be included as a part
      of the routine pre-surgical investigation of the B.N. diseases, for its non
      invasive nature, easiness to perform, and highly useful information.

PMID- 9273093
TI  - [Echo-color doppler in the topographic study of varicocele].
AB  - The echo color doppler allows an easy topographical distinction of the spermatic
      reflux (in front of the deferens) from cremasteric one (back to the deferens).
      This distinction consents a rational surgical choice, the selective interruption
      of the refluent vein and a less morbidity due to the surgical intervention. We
      evaluated 20 infertile patients (mean age 23 years) with echo color doppler
      testicular vessels (B & K 7.5 Mhz transducer). Seven varicoceles were clinically
      evident, 13 varicoceles were subclinic. After locating the deferens, we evaluated
      the venous reflux in the spermatic and cremasteric veins. The evaluation has been
      performed at rest and during Valsava maneuver. We used, in the correction of the
      anterior (spermatic) reflux, a retroperitoneal surgical access, while in the back
      (cremasteric) reflux isolated or combined, we performed middle or under inguinal
      access. The mean follow up has been of 4 months. In all cases the veins with
      reflux have been easily characterized. In 16 patients (80%) the spermatic vein
      was concerned; in an isolated case (5%) the reflux concerned only the cremasteric
      vein, in 3 patients (15%), with clinical varicocele, the reflux was present in
      both the veins (Coolsaet III type). In the 16 spermatic varicoceles, treated with
      retroperitoneal access (Palomo), the echo color doppler check demonstrated the
      absence of venous reflux. In the 4 varicoceles regarding the isolated or
      associate cremasteric vein treated with middle or under inguinal access, the
      existence of extra funicular varix was highlighted and after surgery the echo
      color doppler check was negative. In our few cases the echo color doppler
      diagnosis demonstrated a total correspondence with the surgical finds and with
      the doppler follow up. This diagnostic approach allows to reserve the
      retroperitoneal surgery to the spermatic pure reflux avoiding the false relapses
      due to the persistence of an undiagnosed cremasteric reflux. The middle or under
      inguinal approaches, generally loaded from a greatest morbidity, could be only
      employed in presence of an isolated or combined cremasteric reflux.

PMID- 9273094
TI  - [Echography in the diagnosis and follow-up of renal biopsy complications].
AB  - The introduction of echography represented a focal step in the management of
      renal biopsy, resulting in easier and faster procedures. Chiefly, echography
      allows the diagnosis and monitoring of complications of bioptic procedure. Here
      we present a series of 722 consecutive echo-guided renal biopsies, carried out
      from 1990 to 1995, 97 of which on kidney allografts. Echographic examination,
      performed 24 to 48 hours after renal biopsy, enable to diagnose the presence of
      perirenal hematoma in 30% of patients. Of these, only 10% presented with clinical
      symptoms and/or signs (reduction of Hct and arterial pressure, local pain). Our
      protocol comprises an echographic follow-up to control the evolution of hematoma,
      that usually resolves within 15-40 days, according to the initial size of the
      lesion. One time we observed an intra-parenchimal hematoma, which resulted in
      kidney rupture and consequent nephrectomy. 14% of all patients complained with
      macrohematuria: in 10% of these cases, echography showed the presence of coaguli
      in the urinary tract, which was associated with the clinical features of renal
      colic pain. Only in two cases of persistent macrohematuria, the echography
      together with echo- and color-doppler, allowed the diagnosis of the arterio
      venous fistula. In conclusion, our experience demonstrates that the echographic
      examination allows not only to simplify the bioptic procedure, but also to early
      diagnose the complications due to this invasive manouvre.

PMID- 9273095
TI  - [Fetal uropathies: anatomo-pathologic background].
AB  - The kidney malformations are complex anatomo-clinical entities that can be
      described with different classification approaches, based on morphological or
      etiopathogenetic criteria. The most serious fetal uropathies can be associated
      with the oligohydramnios sequence, due to insufficient urine escretion, related,
      for example to bilateral renal agenesis. A second malformation sequence can also
      be present, the so-called prune belly syndrome, in which an early urethral
      obstruction can produce abnormal bladder distension and finally renal dysplasia
      and globous dilation of the abdomen. The anatomo-pathological experience of the
      last ten years in the Institute of Pathological Anatomy of the University of Bari
      is based upon 154 cases of congenital uropathies in second trimester fetuses.
      Almost 80% of these cases presented also other associated anomalies, both
      chromosomal and non chromosomal syndromic or in casual combination. The possible
      echographic recognition of these pathologies, together with genetic and
      anatomopathological studies allow to categorize the fetal uropathies in two
      groups: the first characterized by an early or late obstruction of the urinary
      tract, in "sensu strictu" the true obstructive uropathies, and the second, formed
      by different morphologies all genetically determined.

PMID- 9273096
TI  - Policy. Unwelcome relief?

PMID- 9273097
TI  - Integrated systems. Doing good--and doing it well.

PMID- 9273098
TI  - Management ... health care organizations may value their volunteers.

PMID- 9273099
TI  - [Measure of abdominal cavity volumes by gynecologic laparoscopy].

PMID- 9273100
TI  - [Follow-up of a cohort of 422 children aged from 6 to 13 and conceived by in
      vitro fertilization].

PMID- 9273101
TI  - [Helping an infertile couple].

PMID- 9273102
TI  - [Anti-papillomavirus immunologic response and natural history of cervical
      lesions].

PMID- 9273103
TI  - [Infertility and small myoma: role of myomectomy].

PMID- 9273104
TI  - [In an infertile woman, does the presence of one or several myomas of less than
      three cm in diameter justify a myomectomy?].

PMID- 9273105
TI  - [Do progestins have drawbacks?].

PMID- 9273106
TI  - [Can microcolpohysteroscopy be used to screen cervical lesions?].

PMID- 9273108
TI  - [Laparoscopic surgery of ovarian tumors during pregnancy].
AB  - During the first trimester of the pregnancy, the management of benign ovarian
      cyst can be performed by laparoscopy. When ovarian tumor is bulky, suspicious and
      after 16 to 20 weeks this treatment must be realised by laparotomy.

PMID- 9273107
TI  - [Comparative randomized controlled study between human follicle- stimulating
      hormone (FSH-HP) and human menopausal gonadotropins (hMG) in in vitro
      fertilization].
AB  - We present the results of a prospective randomized trial comparing the issue of
      IVF-ET and of ICSI when either highly purified human folliculostimulin (FSH-HP)
      or human menopausal gonadotrophin (hMG) is used. There seems to be a trend to a
      better rate of ongoing pregnancies when FSH-HP is used although not statistically
      significant. The study has been stopped due to the lack of hMG.

PMID- 9273109
TI  - [Is fetal fibronectin a valid test predictive of premature labor?].
AB  - This study sought to determine the value of oncofetal fibronectin as predictor of
      preterm delivery in patients presenting with preterm labor. Patients admitted for
      preterm labor with intact membrane between 24 and 34 weeks gestation were
      included. A dacron swab applied to the external os for 10 seconds. The fetal
      fibronectin is detected bill a biologic membrane test. 90 patients were included.
      25 (28%) had positive fetal fibronectin, and 13 (52%) had preterm delivery
      (specificity and positive value 81% and 52% respectively). Among 65 (72%) with
      negative fetal fibronectin, only 12 (18%) had preterm delivery (sensitivity 81%
      and negative predictive value 81%: p < 0.001). Median interval between sampling
      and delivery was 5 days in the positive compared to 23 in the false negative
      group. The presence of fetal fibronectin in the cervico-vaginal mucus strongly
      suggest an eminent delivery within few days after sampling. The sensitivity of
      the test is the 62% and still more interesting the negative predictive value is
      86% (p < 0.001). The fetal fibronectin is a useful test to help the obstetrician
      discriminating true from false labor in patients with high risk preterm delivery.
      A negative test is very reassuring according to its high negative predictive
      value. Allowing to avoid unuseful tocolyse and long hospital.

PMID- 9273111
TI  - [Study of HIV localization in sperm].
AB  - The aim of the study was to investigate the presence and the localization of HIV
      in human ejaculate and its different components. Sixty-three ejaculates from 19
      HIV-positive patients have been studied. By using cellular as well as molecular
      biology methods, we never detected HIV in living and mobile spermatozoa although
      we sometime found the virus in seminal liquid and in nuclear fractions. Up to
      date, frozen sperms free of HIV particles from 11 HIV-positive male partners were
      used to inseminate safely and with success the 11 HIV-negative female partners
      (no female partner as well as babies contamination). In conclusion, our procedure
      of HIV-free spermatozoa screening allowed discordant couples to have HIV-negative
      descendants. In contrast to the natural coitus in ovulated period or to
      insemination with washed spermatozoa that are really "Russian roulette", our
      procedure ensure a total security of no contamination for the pregnant mother.

PMID- 9273110
TI  - [Urinary complications during laparoscopy: a urachal diverticula injury].
AB  - The authors report a bladder injury during laparoscopic procedure. A laparotomy
      is performed immediately and shows an urachal anomaly with the bladder reaching
      the umbilic. One of the accessory trocars perforates the bladder in its unusual
      position. Surgical repair is made and the patient discharged without sequelae 12
      days later. Rate of bladder injury increases with development of advanced
      laparoscopy as Burch and hysterectomy. Careful drainage with folley catheter
      during all laparoscopic procedures present greater than morbidity. Previous
      laparotomy may change the usual position of the bladder. Care must be taken in
      case of wall anomalies as in our observation. Per-operative suspicion of bladder
      injury (hematuria, presence of gas in the urinary catheter collection bag) can be
      proved with the injection of methylene blue in the folley catheter. Laparoscopic
      repair is possible for an experienced surgeon, associated with 10 days continuous
      urinary drainage and quinolone antibiotherapy. Morbidity of unknown bladder
      injury is great with some death-case reports. All diagnosis technique possible
      must be used to light these clinical situations, urinary peritonitis
      symptomatology is often non specific.

PMID- 9273112
TI  - [Female sterilization in Burkina Faso. Report of 142 cases].
AB  - Through a transversal study over a twelve month period, the authors report 142
      cases of female sterilization (FS) in Burkina Faso. The aims of this study were
      to determine the profile of women undergoing FS and to precise the indications
      and the immediate outcome. The study took place in the two main gynecologic and
      obstetric units of the country. Various data about the socio-demographic
      characteristics of the women, their reproductive history, the indications for the
      FS and the short term follow up were recorded. The woman undergoing tubal
      ligation (TL) is 36 years old, gravida 7 para 7 with 5 children (3 boys for 2
      girls). Her occupation is housewifery, she is married and is illiterate in 84.4%
      of the cases. This woman has no prior history of contraceptive use in 71% of the
      cases. FS was performed for medical reasons in 50% of the cases whereas economic
      reason was invoked by only 5% of the couples. Prior to the TL oral informed
      consent was obtained from both the woman and her husband. The TL was performed
      during caesarean section in 55.6%, in the postpartum period in 34.5% of the
      cases. Two wound abscesses occurred. With a follow up ranging from 2 to 14
      months, no pregnancy has been reported. To give a chance to FS to be popular in
      Burkina Faso, the authors made some suggestions.

PMID- 9273114
TI  - New HIV/AIDS strategy launched.

PMID- 9273113
TI  - [Review of the latest treatments of vulvovaginal mycoses: role of fenticonazole
      nitrate (Lomexin) in their treatment].
AB  - Candidal vulvovaginitis result from the deficiency of hort defense mechanisms in
      front of the activity factors of candida. Filamentation and then adhesion of
      candida to vaginal mucosa is the most important step in the process of infection.
      The principal virulence factors of candida are its genotypical and phenotypical
      instability as well as proteinase secretion facilitating adhesion and vaginal
      mucosa invading. Hort defense mechanisms are essentially constituted by vaginal
      flora and local cellular immunity. A weakening even moderate of this immunity can
      favor the spontaneous transformation from asymptomatic colonization to
      symptomatic vaginitis. The most utilized treatments are imidazol derivates in
      short courses. The fenticonazole nitrate has the particularity and the recently
      discovered advantage over the other agents available in single dose regimen to
      inhihate in vitro the proteinase secretion in a dose dependent manner. The
      different clinical studies carried out in comparative or non comparative studies
      have demonstrated its efficiency and tolerance. The most recent studies stress
      the swiftness of symptoms disappearance.

PMID- 9273115
TI  - Reciprocal control of colon-specific sulfomucin and sialosyl-Tn antigen
      expression in human colorectal neoplasia.
AB  - Histochemical reports claim that sulfomucins decrease and sialylated mucins
      increase during colon carcinogenesis. We examined the expression of colon
      specific sulfomucins and sialosyl Tn antigen (STN) in normal small intestine,
      normal colorectal mucosa and colorectal tumours at different stages of
      progression immunohistochemically, using MAb 91.9H specific for colonic
      sulfomucins and MAb TKH-2 for STN. No expression of sulfomucins recognized by MAb
      91.9H was found in normal small intestine, whereas STN staining was pronounced.
      The converse was the case in normal colorectal mucosa. Sulfomucins were still
      found in adenomas, but the amounts decreased with depth of invasion in cancers (P
      < 0.001). In contrast, no STN could be detected in benign lesions, but staining
      became increasingly evident with invasion (P < 0.001). This reciprocal control of
      expression of colon-specific sulfomucins and STN evident in tumour progression
      indicates that the mucous phenotype shifts from the colonic to the small
      intestinal type.

PMID- 9273116
TI  - [Evaluation of a supervision program of health centers at the district level in
      Madagascar].
AB  - Poor supervision and follow-up have long been recognized as major weaknesses in
      the development of primary health care in many countries. A program has therefore
      been specifically developed to strengthen the supervision activities of 18 rural
      health centers in Madagascar. District health officers were appropriately trained
      and then conducted two-monthly supervision visits. The emphasis of the training
      program was on problem solving, program integration and on-site training. The
      effects of the supervision program was assessed quantitatively and objectively.
      Various activities of each health center were scored before intervention, and one
      year after implementation of the supervision program. The improvement in most
      health centers was substantial, both in quantitative coverage and qualitative
      practice. Nevertheless, some centers appear to have been resistant to change.

PMID- 9273117
TI  - [Epidemiologic surveillance of early neonatal mortality at the university
      hospital center in Dakar (Senegal)].
AB  - Neonatal precocious mortality (PNM) is a major public health problem in
      developing countries: the PNM rate is 57 per 1,000 live births, as compared to 11
      per 1,000 in industrialized countries. In Senegal the rate is 35 per 1,000. A
      continuous epidemiological survey was started in 1987 in the Obstetrics and
      Gynecology Clinic of the Dakar University Teaching Hospital (Neonatology and
      Prematurity Unit) (Senegal). The aim was to identify the main risk factors for
      PNM, and thereby define the actions required to reduce the incidence. In 1995,
      there were 177 cases of PNM, which was 12.19% of admissions to the Neonatology
      and Prematurity Unit, and 41 per thousand live births. The most frequent causes
      were premature birth (62.71%) acute fetal suffering (27.20%) and neonatal
      infection (6.22%). The rate of PNM could be reduced by: improved organization of
      prenatal advice to identify pregnancies at risk (of premature delivery and
      obstetric disease); improved quality of neonatal resuscitation; improved practice
      for prevention of infectious disease.

PMID- 9273119
TI  - [10 years' research in the social sciences on AIDS in Burkina Faso. Elements for
      prevention].
AB  - The first cases of AIDS in Burkina Faso were reported in 1986. During the past
      ten years, there have been several types of research conducted in Burkina Faso in
      the field of social sciences, including KABP, focus groups, and ethnographic
      studies. This article reviews approximately 100 publications and presents the
      results most relevant to prevention. Although general knowledge of the disease,
      its transmission and means of protection has improved, part of the population
      remains poorly informed; erroneous ideas remain prevalent and certain concepts,
      for example asymptomatic infection, are ignored. Young women in rural areas have
      the poorest knowledge. Understanding the information is conditioned by underlying
      perceptions of blood and physiology, the "components of the person", pre-existent
      and sexually transmitted diseases, and modes of transmission. Research on
      sexuality has elucidated the age at which individuals become sexually active, and
      paramatrimonial practices. The prevalence of STD is high. STD are mostly treated
      by traditional practitioners or by automedication. Family planning is
      insufficiently developed. AIDS prevention should be integrated into wider
      considerations of reproductive health. The popular perception that "Others" are
      responsible for bringing AIDS into the country has often been reinforced by
      health messages. Consequently, people do not sufficiently consider themselves
      vulnerable to HIV infection. The populations that are most vulnerable, for
      various reasons that have been analysed, include young girls and women, married
      women, prostitutes, truck drivers, and young men from rural areas. The message
      "Fidelity or condom" has been widely used. However, it has hindered the
      generalisation of the use of condoms, because asking for a condom consequently
      implies distrust of the partner. The interpretation of fidelity is diverse, and
      many people who choose this means of prevention believe erroneously that they are
      protected. Studies of the social impact of AIDS reveal fragmentation of society,
      reactions causing social exclusion and discriminative practices, and no social
      visibility of HIV infected persons. After ten years of preventive actions, the
      prevalence of HIV is still increasing, evidence of the failure of the preventive
      strategies. It is no longer sufficient to see prevention as the transfer of
      knowledge from professionals to the population. Preventive strategies such as
      voluntary testing and the participation of HIV+ persons in informative actions
      need to be developed. Prevention should be understood on new bases. The concept
      of "vulnerability" might help the definition of in-depth actions and also focus
      interventions. The idea of developing social cohesion to confront the epidemic
      may help avoid some of the adverse consequences of previous actions. Do these
      concepts conform to current AIDS prevention attitudes? To answer this question,
      social scientists should study the ideologies, knowledge, beliefs, and practices
      of institutions and professionals working in the field of AIDS prevention.

PMID- 9273118
TI  - [The reduction of mother-child transmission of HIV infection in developing
      countries: potential intervention strategies, obstacles to implementation and
      perspectives. The Reduction of Mother-Child Transmission of HIV Infection in
      Africa Group].
AB  - Mother to child transmission (MCT) of Human Immunodeficiency Virus (HIV) is the
      main cause of the spread of the HIV epidemic in the pediatric population. It is
      estimated that to date, three million children worldwide have been infected by
      HIV. The epidemic burden in developing countries is dramatic. Ninety-five percent
      of the world's HIV-infected women are living in developing countries. In
      industrialized countries, antiretroviral treatment of pregnant women and newborns
      with azidothymidine (AZT, ACTG 076 regimen) and discouraging breast feeding by
      HIV-infected mothers are effectively reducing MCT of HIV. However, there are
      three major obstacles to the systematic application of these strategies in
      developing countries: (a) difficulties in implementing the complex AZT
      administration and its corollary the avoidance of breast feeding; (b) the
      complexity of the logistics of the ACTG 076 regimen; (c) cost. Indeed, in
      developing countries the socioeconomic situation of the populations are
      precarious and health structures and services are underdeveloped. In addition,
      the anxiety and the reluctance of general population in the face of the HIV
      problem and the high prevalence of maternal anemia reduce the acceptability and
      safety of AZT treatment for pregnant women in developing regions. Only
      interventions that are applicable, acceptable, safe, affordable, of low cost and
      integrated into health system will be able to reduce HIV MCT. We now know that
      MCT occurs mostly during the perinatal period and the maternal viral load in
      blood, in cervical secretions and in breast milk appears to be the main
      determinant of transmission. Maternal vitamin A deficiency may also favor MCT of
      HIV. It is however possible that this association is confounded by the
      relationship between advanced maternal HIV disease (a known risk factor for
      transmission) and vitamin A deficiency. In spite of these uncertainties
      concerning determinants of MCT of HIV, several interventions have been designed.
      The first involves treating the mother with antiretroviral drugs for the
      perinatal period. The second is vaginal disinfection by application of virucidal
      antiseptics during the perinatal period. The third is to give vitamin A
      supplements to pregnant women and children. Finally, passive immunotherapy with
      anti-HIV antibodies applied to pregnant women and/or new born, may be beneficial.
      The feasibility, safety and efficacy of these potential interventions have not
      yet been demonstrated in developing countries. In view of the dramatic spread of
      HIV infection in these countries, the evaluation of these interventions is of
      utmost priority. These trials are necessary because of the public health
      emergency but should be performed in strict respect of human rights and medical
      ethics.

PMID- 9273120
TI  - [Foreign international bibliographic databases. Index Medicus: presentation and
      use (CD-ROM edition)].
AB  - This paper provides technical assistance for bibliographic retrieval using the
      Medline CDRom, Medfive, with Ovid Search Software. Using a particular search as
      an example, we show, step by step and screen by screen, how to work using all the
      available features of this valuable bibliographic search tool.

PMID- 9273121
TI  - [One world in hope?].

PMID- 9273122
TI  - [Production of Plasmodium falciparum gametocytes: adaptation of a diabolical
      dissemination process of endemic malaria?].

PMID- 9273123
TI  - [Is there the threat of infectious diseases in Africa?].

PMID- 9273124
TI  - [Non-tumor dermatoses diagnosed in the pathologic anatomy laboratory of the
      Tokoin University hospital center, Lome (Togo)].
AB  - The non-tumorous skin diseases are common in hospital consultation in tropical
      countries. These infections constitute a great health problem in black Africa.
      Their diagnosis is often clinically easy, but sometimes histologically
      examination is necessary to have the positive diagnosis. In Togo, a retrospective
      study conducted during ten years, allowed to note 516 cases of non-tumoural
      dermatosis which were histologically diagnosed. The principal infections were:
      inflammatory dermatosis 339 cases (213 cases were not specific against 108
      specific cases predominated by leprosy: 82 cases), epidermal dermatosis (97
      cases, predominated by eczema and psoriasis), dermal lesions (44 cases), lesions
      of dermic and epidermic junction (23 cases), hypodermic (13 cases). The results
      of this study shows the diversity of non-tumorous dermatosis diagnosed by the
      histology. The eradication of these diseases in Africa needs to have efficient
      laboratory diagnosis and research means in every country.

PMID- 9273125
TI  - [Virus transmission in the tropical environment, the socio-ecology of primates
      and the balance of ecosystems].
AB  - We studied the contribution of non human primates to the transmission of yellow
      fever and HIV in the wild. We demonstrate the consequences of the modification of
      ecosystems on the emergence of new viral diseases and the reappearance of
      diseases believed to be eradicated. In the primary forest, the natural yellow
      fever cycle is limited to monkeys and mosquitoes living high in the canopy.
      Transmission to man is an anomaly, requiring the circumstances found in the
      forest and savanna contact zones, where man has changed the forest to a mosaic
      and decimated the simian population, favoring contact between mosquitoes and man.
      In these contact zones, the amaril virus circulates in episodic cycles. During
      each episode, most of the local monkeys are infected, and thereby acquire
      immunity. Yellow fever can only reappear subsequently when a sufficiently large
      new generation of non-immune young monkeys is available. Monkeys do not become
      ill when infected, presumably as a result of typical host-parasite cross
      selection having led to the development of a balance between the parasite and its
      host. AIDS is a transmissible viral disease which appeared recently. Various
      African non-human primates are hosts to SIV, a retrovirus closely related to HIV
      which causes AIDS in man. SIV-infected African monkeys do not develop AIDS.
      However, when used to infect species from other continents (for example Asian
      macaco monkeys) SIV can cause AIDS. Does pathogenicity appear during transmission
      of the virus from one primate host to another, and is this the case for human
      AIDS? Experimental inoculations, the demonstration of SIVagm in other species,
      the mosaic structure of the genome (implying cross species recombinations), and
      the high probability of cross-species transmission of the viruses in the wild all
      favor this idea. Possibly counterbalancing the pessimism about the development of
      an HIV1 vaccine in the near future, the non-human SIV models holds out some hope.
      The emergence of new diseases, such as Ebola, or diseases from other niches, and
      the reappearance of diseases believed to be eradicated, are frequent when man
      modifies the ecosystem, the structure and balance of which he does not control,
      and when he puts into contact species which have never met before.

PMID- 9273127
TI  - [Epidemiologic indicators of tuberculosis].
AB  - The indicators used in the struggle against tuberculosis, particularly in
      developing countries, can be separated into two groups. First, the variables, are
      indicators of the overall damage caused by the disease in the community.
      Secondly, the parameters, are the calculated indicators of the risk for
      tuberculosis faced by the individual. Their presentation here follows the
      pragmatic concerns of the coordinators of the programs: evaluating the scale of
      the tuberculosis problem; ensuring its surveillance and the supervision of a
      prevention program; and diffusing the information required to stir the program
      workers and the population into action to fight tuberculosis. Among the
      variables, the incidence of mortality lost significance. The emphasis is now on
      the incidence of the new cases of contagious pulmonary tuberculosis as well as
      the calculation of the Annual Risk of Infection (ARI). The ARI, despite serious
      criticisms, remains one of the best indicators for the study of tuberculosis. The
      data obtained from an active program must be standardized to allow comparisons of
      the declared cases as well as their follow-up after the initiation of the
      treatment. The parameters enable a mathematical representation of the different
      stages in the natural development of the disease: the risk to be infected; the
      risk of becoming ill; and the development of the illness. These parameters can be
      advantageously used to mobilize the people into action. The pandemic of HIV
      drastically changed the natural history of tuberculosis. HIV infection is the
      most important factor of the transition from tuberculosis infection to active
      tuberculosis. The HIV pandemic also modified the epidemiological estimations of
      tuberculosis. In particular, it reinforced the criticisms made against the ARI.
      The surveillance of the prevalence of HIV among tuberculosis patients is thus
      important data.

PMID- 9273128
TI  - [Use of pupillometry in the diagnosis of neurologic disorders caused by
      organophosphorus compound poisoning].
AB  - By means of pupillometry the authors evaluated pupil functions in subjects
      exposed to organophosphorus compounds at work. Revealed pupillometric features
      are helpful in detection of poisoning with organophosphorus compounds.

PMID- 9273126
TI  - [Primary chemoprevention of tuberculosis in HIV-infected patients in non
      industrialized countries].
AB  - In randomized placebo-controlled trials in Haiti, Zambia and Uganda, prophylactic
      use of isoniazid (INH) for 6 to 12 months reduced the annual incidence of
      tuberculosis in HIV-infected patients by more than 50 per cent. For several
      years, WHO, IUTATLD and CDC have recommended that HIV-positive patients testing
      positive in a PPD test should be treated with INH as a form of anti-tuberculosis
      chemoprophylaxis (ATC). Whilst these recommendations are easy to follow in
      industrialized countries, widespread use of ATC in developing countries remains
      problematic because: (i) It is unknown what proportion of patients are likely to
      be re-infected at the end of ATC in countries where TB is endemic; (ii) It is
      possible that resistant bacilli may be selected due to the incomplete exclusion
      from the ATC program of patients with active TB at enrollment; (iii) It is
      difficult to identify asymptomatic carriers of M. tuberculosis at enrollment;
      (iv) It is doubtful that all patients will comply with a treatment regime which
      lasts several months; (v) The cost of a widespread ATC program, whose full
      benefit remains to be evaluated, may be difficult to justify. This paper attempts
      to review these issues and demonstrates the need for more population-based
      clinical trials in the field.

PMID- 9273129
TI  - [Mental disorders in workers exposed to chemicals at work].
AB  - The article considers data on boundary psychic disorders in subjects exposed to
      chemicals of I-II jeopardy classes. Chemical factor appears to increase risk of
      psychiatric diseases. The authors suggest periodic psychiatric examination of
      workers engaged into hazardous chemical production for better occupational
      selection, early diagnosis and treatment of boundary psychic disorders.

PMID- 9273131
TI  - [Structure of occupational diseases in patients examined and treated at the
      Institute clinic of hygiene, occupational diseases and human ecology].
AB  - The authors analyze data on patients diagnosed as having occupational disease in
      1970-1995 and grouped according to age, sex, length of service, occupational
      hazards. Incidence of various syndromes in occupational diseases is calculated.
      The authors detail some items obscuring diagnosis of occupational diseases and
      necessitate referral to various professionals for precise and early diagnosis.

PMID- 9273130
TI  - [Evaluation of chemical mutagenic factor in workers].
AB  - The authors analysed retrospectively a reproductive function among female workers
      of chemical plant. The subjects were exposed to mutagenic and carcinogenic
      chemicals before pregnancy and during early term pregnancy. Occurrence of
      complications during pregnancy and delivery was significantly higher in the
      exposed group vs. the reference one. Incidence of congenital abnormalities among
      children in the exposed group tended to increase. Cytogenetic alterations were
      reliably more frequent in peripheral WBC and in embryonal tissues obtained during
      abortions in workers of the plant, if compared to the parameters of the reference
      group.

PMID- 9273132
TI  - [Importance of toxicological studies in animals for elaboration of pathogenetic
      therapy of hydrazine intoxication].
AB  - Pathogenesis of poisoning with hydrazine seems complicated. Hydrazines inhibit
      pyridoxal-dependent enzymes, interfere with carbohydrates transformation and
      lipid metabolism, alter the processes of energy metabolism. Treatment of
      poisoning with hydrazine is effective only when containing drug combinations.
      Based experimentally, recommendations on the combination (phenazepam, be methyl,
      piracetam, ionol) were supported by chemical testing of the drugs.

PMID- 9273133
TI  - [Compensation of health injuries caused by ecological hazards].

PMID- 9273134
TI  - [Chemical accidents and organization of medical services].
AB  - Having analyzed 274 accidents, the authors summarize accident definitions and
      stages of chemical accident, presents parameters of chemical risk, determine
      chemicals frequently involved into accidents, evaluate occurrence and severity of
      chemical disorders. The article outlines suggestions on accidents account in this
      country.

PMID- 9273135
TI  - [Psychophysiological changes in occupational diseases of chemical etiology].
AB  - Use of various psychophysiologic methods enabled to specify psychic response of
      workers exposed to chemicals and chronic poisoning patients. Chronic poisonings
      with 1,1-dimethylhydrazine, hydrocarbons, Trichlorfon, mercury, nitroesters have
      specific traits, and the patients could be grouped by means of cluster analysis.
      Handy techniques evaluating attention and memory could be recommended for
      everyday practical needs.

PMID- 9273136
TI  - [Clinical and psychological criteria of early detection of hazardous effects of
      components of synthetic hydrocarbon fuel].
AB  - The article shows increasing degree of psychic disorders in workers exposed to
      highly toxic chemicals. The symptoms develop from mild emotional disturbances in
      apparently healthy individuals then through premorbid psychotic manifestations to
      complete psychiatric syndrome of chronic occupational poisoning. The authors
      necessitate early diagnosis of the chronic occupational poisoning.

PMID- 9273137
TI  - [Epidemiological evaluation of long-term effects of hazardous substances].
AB  - The article deals with epidemiologic evaluation of long-term chemical effects.
      The authors stress difficulties in setting the "cause-effect" relationships and
      define some typical mistakes in such research.

PMID- 9273138
TI  - [Use of "Criteria for evaluation of regional ecological situation in detection of
      dramatic ecologic zones and zones of ecologic disaster" in assessment of ecologic
      situation in towns neighboring major chemical enterprises].

PMID- 9273139
TI  - [Neonatal pathology in town neighboring a major chemical plant].

PMID- 9273140
TI  - [Significance of the determination of neuromediators in prognostication of
      workers' health status].

PMID- 9273141
TI  - [Acute poisoning by neuroparalytic agents and its long-term effects].
AB  - The authors analyzed over 200 cases of acute poisoning with sarin, soman and VX
      chemical, determined risk of the poisoning in various conditions. The clinical
      manifestations of acute poisoning and the long-term effects are presented.

PMID- 9273142
TI  - [Chronic poisoning by organophosphoric VX].
AB  - Long-term observation of workers engaged into production of VX chemical diagnosed
      slow progressing manifestation of chronic occupational poisoning with the
      chemical. The characteristic nervous, digestive, locomotory, visual and
      cardiovascular symptoms were revealed. The authors presented laboratory and
      instrumental data on the cases. As the treatment appeared ineffective, further
      adjustment and improvement of the therapy is required. The article demonstrated
      the main underlying metabolic disorders that could be addressed by the
      pathogenetic therapy.

PMID- 9273143
TI  - Adenocarcinoma of the small bowel presenting as ureteric colic.

PMID- 9273144
TI  - Urological Research Society annual scientific meeting. London, United Kingdom, 10
      January 1997. Abstracts.

PMID- 9273145
TI  - Disruption of the IP3 receptor gene of Drosophila affects larval metamorphosis
      and ecdysone release.
AB  - BACKGROUND: The inositol 1,4,5-trisphosphate (IP3) receptor is an intracellular
      calcium channel that couples cell membrane receptors, via the second messenger
      IP3, to calcium signal transduction pathways within many types of cells. IP3
      receptor function has been implicated in development, but the physiological
      processes affected by its function have yet to be elucidated. In order to
      identify these processes, we generated mutants in the IP3 receptor gene (itpr) of
      Drosophila and studied their phenotype during development. RESULTS: All itpr
      mutant alleles were lethal. Lethality occurred primarily during the larval stages
      and was preceded by delayed moulting. Insect moulting occurs in response to the
      periodic release of the steroid hormone ecdysone which, in Drosophila, is
      synthesized and secreted by the ring gland. The observation of delayed moulting
      in the mutants, coupled with the expression of the IP3 receptor in the larval
      ring gland led us to examine the effect of the itpr alleles on ecdysone levels.
      On feeding ecdysone to mutant larvae, a partial rescue of the itpr phenotype was
      observed. In order to assess ecdysone levels at all larval stages, we examined
      transcripts of an ecdysone-inducible gene, E74; these transcripts were
      downregulated in larvae expressing each of the itpr alleles. CONCLUSIONS: Our
      data show that disruption of the Drosophila IP3 receptor gene leads to lowered
      levels of ecdysone. Synthesis and release of ecdysone from the ring gland is
      thought to occur in response to a neurosecretory peptide hormone secreted by the
      brain. We propose that this peptide hormone requires an IP3 signalling pathway
      for ecdysone synthesis and release in Drosophila and other insects. This signal
      transduction mechanism which links neuropeptide hormones to steroid hormone
      secretion might be evolutionarily conserved.

PMID- 9273147
TI  - [The standards of medical-social assistance to retirees].
AB  - Offers norm-setting parameters reflecting the requirements of elderly subjects in
      medicosocial care. These standards may be the social guarantee of rendering
      medicosocial care to elderly subjects under conditions of socioeconomic
      reformation and introduction of obligatory medical insurance.

PMID- 9273148
TI  - [Transmissible and natural infections in Siberia and the Far East].
AB  - The common and specific features in the time course and structure of morbidity as
      regards tick-borne rickettsiasis, tick-borne encephalitis, and Lyme disease in
      Siberia and Far East are discussed. The differentiation of nosological areas of
      tick-borne rickettsiasis and encephalitis is demonstrated and 9 variants of
      ratios of epidemiological zones of different hazard of infection established. The
      subject of comparative epidemiology of focal infections is formulated. General
      conceptual approaches to epidemiologic survey as the basis for optimizing
      preventive measures are outlined.

PMID- 9273150
TI  - [Current problems in the optimization of the function of the regional medical
      association].

PMID- 9273149
TI  - [The attitude of health personnel and population toward the economic reform in
      public health system. (The results of a survey in Chelyabinsk)].
AB  - Sociologic survey of the knowledge of the population and medical workers about
      the new economical relations in public health system, including medical
      insurance, showed that both the population and medics understand the necessity of
      public health reformation, introduction of new economic relations, and medical
      insurance. The major part of the population is ready to pay for medical service,
      but cannot afford it.

PMID- 9273151
TI  - [The advances in the health care management in the Russian Federation on the
      basis of the analysis of the health personnel].
AB  - Present the purpose, tasks, methods and programs of a comprehensive study of
      medical personnel organization and management. The activities of staff
      departments are proposed to be singled out as a specific service. Some findings
      of the study are presented, as are the results attained with the introduction
      into practice of a model of staff service in number of regions and the experience
      gained with training of specialists for personnel departments.

PMID- 9273152
TI  - [On the concept of the formation of municipal system of health care].

PMID- 9273153
TI  - [The management in clinical trials of pharmacological agents].
AB  - The author analyzes the experience gained by foreign countries in the creation of
      a new management system in all spheres of public health, including clinical
      trials and use of drugs. A term "High-Quality Clinical Practice" is used in the
      European Community, reflecting the standard or the norm of clinical studies and
      designed as a complex of regulations for the organization and implementation of
      clinical studies. High-Quality Clinical Practice implies all reasonable measures
      providing the accuracy of experimental data and guarantees the rights of the
      participants in the trials. Studies carried out in conformity with the
      requirements of High-Quality Clinical Practice bring about reliable results and
      permit the pharmaceutical companies and public health organs use these data.

PMID- 9273154
TI  - [Preventive medicine in the system of transportation].

PMID- 9273155
TI  - [Social-medical aspects of the demographic situation in contemporary Poland].
AB  - New approaches to the solution of a complex of medicosocial problems which should
      be not disregarded when developing the strategy of public health development
      under conditions of reformation of the Russian economy are discussed. An
      intergral system of medicosocial care of the population both at the federal and
      regional levels should be formed and the mechanisms and methods of its
      realization developed in order to pursue an effective medicosocial policy, which
      represents an integral element of the strategy of public health development, with
      due consideration for the social, economic, demographic, ecological,
      sociohygienic, and other factors. The author believes that medicosocial policy
      should be characterized by clear-cut strategic direction as regards all public
      health services.

PMID- 9273157
TI  - [The historical aspects of the formation of public health system and medical
      insurance in Siberia].

PMID- 9273156
TI  - [The structure and curriculum at the medical department of Moscow University in
      the 18th century].

PMID- 9273158
TI  - [The activity of evacuation hospitals in Northern Kazakhstan: an example of a
      successful inter-ethnic cooperation].

PMID- 9273159
TI  - [The organization of fight against typhus in the Samara region during the years
      of the Civil War].

PMID- 9273160
TI  - [Tho social charity movement during the Russian-Japanese War (1904-1905)].

PMID- 9273161
TI  - [The Red Cross Society medals issued to Russian physicians and nurses for their
      selfless medical assistance].

PMID- 9273162
TI  - [For 125th anniversary of Z.G. Frenkel].

PMID- 9273163
TI  - [Social-hygienic features of health, life conditions and medical-social
      assistance to the veterans and disabled veterans of the Great patriotic war in
      Russia].
AB  - Disease incidence in participants and subjects disabled in the Great Patriotic
      War is analyzed as reflected by the records of consultation rate and medical
      check-ups of this population. Sociologic study provided information about the
      subjective assessment of the health status and some sociohygienic and biological
      characteristics of the cohort. The scope of medical care rendered and
      requirements in corrective devices and specific types of social care were
      studied.

PMID- 9273164
TI  - [Cutaneous innervation: anatomy and physiology. Neuropeptides].
AB  - The skin is involved in the tactile sensations and hydric and thermic regulation.
      This structure contains immunological cells with inflammatory activity in
      addition to several bioactive molecules. This review will focus primarily on the
      relation of cutaneous innervation in these processes and its capacity to release
      neuropeptides as functional molecules. This paper will discuss the organization
      of the motor and sensitive fibres, the biosynthesis, molecular modifications,
      regulation and the functions of the best well known neuropeptides. The specific
      function of these molecules in the neurogenic inflammation and how the nervous
      system can influence in several skin diseases is explained. In conclusion, the
      cutaneous innervation can affect processes such as inflammation, cellular
      proliferation and healing. This possibility is likely to be mediated by
      neuropeptides. In the future, a growing list of neuropeptides will be compiled
      and the precise role in cutaneous physiology will be known, but the most
      important of this knowledge is probably the repercussion in the therapies of some
      cutaneous diseases.

PMID- 9273165
TI  - [The main etiopathogenic mechanisms of neurocutaneous diseases].
AB  - Neurocutaneous syndromes constitute a large and complex group of diseases in
      which recent medical advances, particularly in the field of molecular biology and
      genetics, have afforded a deeper understanding of the way in which these diseases
      originate. In this article, we review the advances concerning pathogenic
      mechanisms. First, we discuss the malformations disorders of the central nervous
      system associated with skin disorders, which range from spinal and/or cranial
      dysraphism with skin lesions to fustrated forms of malformations of the neural
      tube, such us membranous aplasia cutis. Neurocutaneous vascular disorders can be
      due to malformational disease, such as in Sturge-Weber syndrome, as well as to
      autoimmune diseases. The analysis of mutations affecting the capacity for
      migration and differentiation of melanocyte precursors enables us to gain a
      better understanding of disorders of the cells of the neural crest, such as
      piebaldism and Waardenburg's syndrome. Mutations in tumor suppressor genes play
      an important part in the development of hamartomatous and neoplastic lesions in
      neurofibromatosis and tuberous sclerosis. Genetic mosaicism, both of the
      functional and the genomic kind, accounts for the great diversity of phenotypes
      and the distribution of neurocutaneous diseases. Lastly, neurocutaneous syndromes
      such as the paracrinopathies form an attractive hypothesis, which is as yet to be
      confirmed.

PMID- 9273166
TI  - [Role of neuropeptides in dermatology].
AB  - Neuropeptides (NP) are a heterogeneous group of proteins functioning as
      neurotransmitters, neuromodulators and neurohormones. More than fifty of these
      molecules have been described, and some have been detected in human skin through
      immunochemistry and radioimmunoassay. In this article we attempt to study the
      role played by some of these substances such as substance P (SP), calcitonin gene
      related peptide (CGRP), neuropeptide Y (NPY), vasoactive intestinal peptide
      (VIP), somatostatin (S), and neurotensin (N). Several NP induce inflammatory
      response with edema and erythema. They can also induce the release of histamine
      by mastocytes, regulate cutaneous blood flow, and participate in sweat regulation
      and nociception. They also exert their action over several cells that participate
      in immunity, acting as mitotic, and chemotactic factors, inhibiting or
      stimulating inflammatory mechanisms. Specific NP have their receptors on
      epidermal cells. We will also try to study certain diseases in which NP play an
      important role in inducing or alleviating lesions, such as psoriasis, atopic
      eczema, alopecia areata, vitiligo, nodular prurigo, aquagenic pruritus,
      hypertrophic scars and other entities.

PMID- 9273167
TI  - [Neural tube dysfunction and cutaneous lesions].
AB  - The aim of our article is to underline the cutaneous lesions accompanying spinal
      disraphysm. We would like to stress the responsibility of physicians,
      particularly dermatologists, pediatricians, orthopedic surgeons, urologists,
      neurologists and neurosurgeons to recognize as early as possible these cutaneous
      stigmata. In this way patients will be studied and treated as soon as possible.
      No cutaneous lesion in the posterior middle line of the back or close to it
      should be removed until any possibly associated malformation has been thoroughly
      studied. Otherwise the diagnosis of a subyacent spinal disraphysm might be unduly
      delayed and thus allow the appearance of irreversible neurological deficits.
      Cutaneous lesions associated with spinal disraphysm are: areas of atrophic skin,
      aplasia cutis congenita, congenital skin scars, dermal pits, dermal sinuses,
      dyschromic lesions, hyperpigmented lesions, abnormal pilifications, vascular
      lesions, subcutaneous lipomas, polipoid lesions simulating tails, neurofibromas,
      melanocitic nevus and some lesions of tumoral origin. Of there the most common
      cutaneous lesion associated with spinal disraphysm is the lipoma, followed by the
      dermal sinuses, the anomalus pilifications and the angiomas.

PMID- 9273168
TI  - [Keratotic neurocutaneous syndromes].
AB  - OBJECTIVE: To review current knowledge of etiologic, clinic, diagnostic and
      therapeutic aspects of ichthyotic diseases with neurologic manifestations.
      DEVELOPMENT: Classic keratotic neurocutaneous syndromes including Sjogren-Larsson
      syndrome, trichotyodystrophy, KID (keratitis, ichthyosis and deafness) syndrome
      and Rud syndrome, are reviewed. Furthermore, we pay attention to syndromes whose
      description and study are of current importance: cardiofaciocutaneous syndrome,
      neutral lipids storage disease with ichthyosis, multiple sulphatase deficiency
      disease and peroxisomal disorders. CONCLUSIONS: Keratotic neurocutaneous
      syndromes knowledge will help to improve its diagnosis and therapeutic approach.

PMID- 9273169
TI  - [Neurocutaneous syndrome with hair alterations].
AB  - There are multiple neurocutaneous syndromes that may show hair alterations such
      as the interglabellar peak or 'widow's peak', which is an alteration of the hair
      implantation, in addition to the genohypotrichosis, hypertrichosis and hair shaft
      dysplasias. In this chapter we will focus on the latter. Out of the unspecific
      hair shaft dysplasias the only ones showing neurological alterations are
      trichorrhexis invaginata, observed in the syndrome of Netherton. Among the
      specific dysplasias we would like to point out monilethrix, and very especially
      the moniliform hair syndrome, the trichorrhexis nodosa, the pili torti and
      trichotiodystrophy. The latter is actually a group of syndromes which associates
      a series of diverse symptoms that have in common hair brittleness, fertility
      problems and physical and mental retardation, and they constitute the basic
      syndrome know as 'BIDS syndrome.

PMID- 9273170
TI  - [Neurocutaneous syndromes with vascular alterations].
AB  - There are several syndromes in which neurological and cutaneous alterations of
      vascular origin, among other symptoms, occur. The key point of this fact is that
      these cutaneous signs permit early diagnosis, thus helping in further recognition
      of more complex syndromes and preventing unnecessary, harmful and costly
      diagnostic procedures or having to wait until the appearance of neurological
      signs. Therefore, these diseases should be classified attending to the most
      notorious vascular lesions they show, though they may show other less frequent
      cutaneous vascular lesions. In this way, these syndromes can be classified as
      associated with nevus flammeus (Sturge-Weber, Shapiro-Shulman, Bonnet-Dechaume
      Blanc, Cobb, Klippel-Trenaunay, Fegeler, Robert), cavernous hemangiomas
      (Maffucci, blue-rubber-bleb-nevus, Proteus, Bannayan-Zonana, Riley-Smith,
      familial cavernous angiomatosis, POEMS syndrome), capillary hemangiomas
      (Rubinstein-Tayabi, Coffin-Siris, PHACE syndrome), telangiectasia (congenital
      telangiectatic cutis marmorata, Rendu-Osler-Weber, ataxia telangiectasia,
      Cockayne, De Sanctis-Cacchione), livedo reticularis (Sneddon, Divry-van-Bogaert),
      angioqueratoma (Fabry disease, Fucosidosis) and hemangioblastoma (Von Hippel
      Lindau). Though we have tried that these vascular lesions should be named as
      angiomas if they are malformations and hemangiomas if they are benign neoplasias,
      they are called following morphological aspects rather than other criteria, due
      to their unknown origin.

PMID- 9273171
TI  - [Dyscromic neurocutaneous syndromes].
AB  - Discromic neurocutaneous syndromes are an heterogeneous group of genetic diseases
      which associate pigmentary anomalies to nervous system disturbances. Development
      of molecular biology has allowed a better understanding and classification of
      this diseases. In this article we review this entities with an emphasis on the
      last clinical and genetic discoveries.

PMID- 9273172
TI  - [Neurocutaneous melanosis].
AB  - Neurocutaneous melanosis is a sporadic neurocutaneous syndrome characterized by
      the presence of giant or multiple melanocytic nevi and excessive proliferation of
      melanotic cells in the central nervous system. Patients usually consult
      dermatologists because the congenital cutaneous nevi. Most neurologic symptoms
      appear in the first two years of life and the prognosis in such cases is poor,
      especially if they are caused by hydrocephalus, which is the main complication.
      All patients with giant or multiple melanocytic nevi should be seen frequently to
      detect promptly the eventual development of neurologic involvement.

PMID- 9273173
TI  - [Diagnosis of neurometabolic and neurodegenerative diseases by cutaneous biopsy].
AB  - Cutaneous biopsy is of great use in the diagnosis of neurodegenerative diseases,
      especially neurometabolic and inborn errors of metabolism. The sweat glands,
      especially the eccrine ones, and certain cellular elements in the adventitial
      dermis like the Schwann cells, axons, endothelium and fibroblasts, are altered in
      inborn errors of metabolism and in certain neurodegenerative diseases. The
      morphology and placement of these deposits, as for example axonal spheroids,
      Lafora bodies, homogeneous cytoplasmic bodies and prismatic bodies, permit to
      diagnosis the disease. Differential diagnosis must be made with simulating
      storage disorders. The study of skin biopsy must be complete and rigorous and
      follow a system of work, that includes electron microscopy, enzymatic
      determination and, occasionally, molecular biology. Valuable information about
      neurodegenerative diseases as muscular dystrophies, axonal neuropathy, Alzheimer
      disease and others can be carried out by skin biopsy. It can be foreseen that in
      the future indications of skin biopsy will be extended to other neurodegenerative
      diseases.

PMID- 9273175
TI  - [Systemic autoimmune diseases with neurocutaneous alterations].
AB  - Autoimmune diseases depend on the pathologic activation of cellular clones,
      potentially harmful, against soft tissues. They can be classified into systemic
      and organ-specific diseases. In the systemic subtype, in which the abnormal
      hyperactivity is not as specific, the most remarkable component of the clinical
      syndrome is frequently the presence of neurological and/or cutaneous
      manifestations. This article reviews the major pathogenic mechanisms involved in
      the principal systemic autoimmune conditions including connective tissue diseases
      (rheumatoid arthritis, systemic lupus erythematosus, polimyositis,
      dermatomyositis, scleroderma, mixed connective tissue disease, Sjogren's
      syndrome, overlap syndromes) and vasculitic syndromes (nodous polyarteritis,
      giant cell arteritis. Wegener's granulomatosis. Behcet disease, microscopic
      polyarteritis, cryoglobulinemia) as well as their clinical manifestations,
      focused mainly on neurocutaneous characteristics.

PMID- 9273174
TI  - [Infections with cutaneous and nervous system alterations].
AB  - OBJECTIVE: We review and update the clinical and diagnostic aspects in the most
      representative neurocutaneous infections, emphasizing the features of
      interdisciplinary interest. METHODS: Human skin is the primary host barrier
      against infection and his importance is critical in the immunocompromised
      population. The genetic hability of pathogen micro-organisms to bind the adhesion
      molecules of cellular membranes defines the anatomic affinity of each species.
      Cutaneous involvement can be crucial for diagnosis in infectious diseases. The
      characteristics of the elemental lesions and the accessible cytology,
      bacteriology and histopathology procedures, usually leads to a specific
      diagnosis. We highlight the cutaneous manifestations of the acute and subacute
      bacterial meningitides. We review the clinico-pathologic characteristics of the
      meningoencephalitidis associated to the viral exanthems. We describe the chronic
      bacterial entities with prominent cutaneous and neural affectation as lepra,
      syphilis and borreliosis, as well as the numerous clinical forms of presentation
      of herpesvirus hominis and varicellazoster. Finally, we stand out the
      transcendency of cutaneous findings in the HIV set. CONCLUSIONS: The appropriate
      interpretation of the infectious cutaneous semiology, supplemented with exams of
      direct samples, allow frequently to reach an ethiologic or orientated diagnosis,
      in a rapid, economic and non-invasive way. This information must be carefully
      incorporated to the study of high-morbidity infections, as there that concerns to
      the nervous system.

PMID- 9273176
TI  - [Adverse cutaneous reactions to drugs in neurology].
AB  - Skin drug reactions are cutaneous rashes caused by drugs, through different
      pathogenic mechanisms that can be classified into two groups: immunologically
      mediated and non-immunologically mediated. In the first part of this chapter we
      are going to study the cutaneous reactions to aromatic antiepileptic drugs,
      namely phenytoin, and focusing attention towards potentially life-threatening
      drug reactions of an immune cause such as toxic epidermal necrolysis and
      hypersensitivity syndrome. Secondly we are going briefly summarize skin reactions
      to drugs usually dealt with in neurological diseases, following a classification
      based on the morphological aspects of the lesions present in each reaction.

PMID- 9273177
TI  - [Neuropeptides in dermatologic therapy].
AB  - The presence of neuropeptides and their specific receptors has been detected in
      the skin and the epithelial tissues. They are involved in innervation,
      immunomodulation, glandular secretion, control of cellular proliferation and
      regulation of blood flow. The fact that they act in so many different ways means
      that neuropeptides and their agonists and antagonists are now being regarded as
      potential therapeutic agents in dermatologic diseases. Among the substances which
      act as antagonists, particular attention should be paid to capsaicin, which has
      therapeutic potential for three types of indication: peripheral neurologic pain,
      affections with a neurogenic inflammatory component and pruriginous dermatosis;
      peptide T with therapeutic potential for psoriasis; and spantide, which might
      prove useful in dermatoses related to substance P. The influence of topical
      corticosteroids on the mechanism of action of neuropeptides can explain its
      efficacy in the treatment of many dermatoses. Among the agonists, the possibility
      of taking advantage of the vasodilatory activity of the calcitonin gene-related
      peptide is being considered in Raynaud's disease and erectile disfunction of the
      penis; and the immunomodulatory and anti-inflammatory action of the alpha
      melanocyte stimulating hormone is being studied as a potential means of
      controlling inflammatory dermatoses of immunological origin.

PMID- 9273178
TI  - [The tolerability of antihypertensive therapy: limits and dimensions of a summary
      phenomenon].

PMID- 9273179
TI  - Current awareness in geriatric psychiatry.

PMID- 9273180
TI  - [Concomitant radiochemotherapy for locally advanced bronchial cancers: current
      results and prospects].
AB  - The prognosis of locally advanced lung cancer is reportedly poor in all
      histologic types. In non-small cell lung cancer, radiation therapy alone results
      in disappointing long-term survival. Three recent randomized trials, however,
      have shown a limited but significant improvement of survival with induction
      chemotherapy, though local control remained poor in these studies as well as in
      small-cell lung cancer treated with chemotherapy and late radiotherapy. Two
      randomized trials focusing on small-cell lung cancer have recently shown
      significant benefit due to the combination of early concurrent mediastinal
      irradiation and chemotherapy, with major improvement in local control and a more
      than 40% 2-year survival rate. The concept of concurrent chemoradiotherapy has
      also been studied in non-small cell carcinoma with several pilot studies leading
      to both encouraging results and improved survival rate (up to 40% at 2 years).
      Ongoing phase III trials are comparing sequential versus concurrent
      chemoradiotherapy and will define the role of radical surgery after
      chemoradiotherapy in locally advanced non-small cell lung cancer.

PMID- 9273181
TI  - [Treatment of lung carcinomas. Proceedings of the 8th Congress of the French
      speaking Oncology Society. Jersey, 15 September 1995].

PMID- 9273182
TI  - [Induction chemotherapy followed by concomitant combined radiotherapy and
      chemotherapy in stage III non-small cell bronchial carcinoma].
AB  - PURPOSE: To determine the efficacy and safety of induction chemotherapy followed
      by concomitant chemoradiotherapy in the treatment of stage III non-small cell
      lung cancer and whether the response to induction chemotherapy can predict the
      response to subsequent chemoradiotherapy and survival. MATERIALS AND METHODS:
      Between December 1987 and June 1993, 46 patients with previously untreated stage
      III non-small cell lung cancer received every 21 days induction chemotherapy
      (ICT) including three cycles of 5-fluorouracil (600 mg/m2/d in short infusion
      from d1 to d5), cisplatin (15 mg/m2/d from d1 to d5), etoposide (50 mg/m2/d from
      d1 to d5) and hydroxyurea (1,500 mg/d from d1 to d5). The first 21 patients also
      received bleomycin (3 mg/m2/d from d1 to d5). All patients received concomitant
      chemotherapy and had chest radiotherapy (CCRT). Patients received irradiation (65
      Gy/33-6 fractions/7 weeks) on d25 after the third cycle of chemotherapy.
      Concomitant chemotherapy was composed of cisplatin (20 mg/m2) and 5-fluorouracil
      (500 mg/m2) that were administered each Monday and Thursday during radiotherapy.
      Maintenance chemotherapy consisted of thiotepa (10 mg/m2) and methotrexate (10
      mg/m2) that were administered every 2 weeks for 6 months. RESULTS: Pulmonary
      toxicity was observed in four out of 21 patients who had received bleomycin and
      subsequently developed pulmonary fibrosis, leading to death for two of them. ICT
      alone produced five complete responses (11%) and 13 partial responses (28%). The
      combination of chemotherapy and radiotherapy led to 19 complete responses (41%)
      and 14 partial responses (30%). Eighteen of the 18 responders (100%) to ICT
      responded to subsequent CCRT, of whom 13 (72%) became complete responders.
      Fifteen of the 28 non-responders to ICT (53%) responded to CCRT, six of them
      being complete responders (21%) (P < 0.001). The median overall survival rate was
      17 months when considering all patients, 25 months in patients responding to ICT
      and 13 months in non-responders. The 2-year survival rates were 28, 55 and 11%,
      respectively (P < 0.05). ICT did not influence the rate of subsequent metastatic
      events. However, locoregional reprogression was lower in responders to ICT. The
      number of metastatic events was not significantly related to response to ICT. By
      contrast, the rate of local failure was higher when there was resistance to ICT
      (75% versus 39%). Out of the 19 complete responders to CCRT (13 responders to ICT
      and six non-responders to ICT), four developed secondary locoregional
      reprogression (21%) and six developed metastatic disease (31%). In complete
      responders to CCRT, the rate of locoregional failure was 15% in responders to ICT
      (2/13) and 33% (2/6) in non-responders to ICT. Four out of the 13 responders to
      CCRT after response to ICT (31%) and two out of the six complete responders to
      CCRT developed metastatic disease after non-response to ICT. CONCLUSION: There is
      a statistically significant relationship not only between the response to ICT and
      the response to CCRT, but also between the response to ICT and the local outcome
      and survival.

PMID- 9273183
TI  - [Radiotherapy in locoregional treatment of inoperable non-small cell lung cancer:
      results from a series of 381 patients].
AB  - PURPOSE: The prognosis of inoperable non-small cell lung cancer (NSCLC) is poor
      and thoracic radiation therapy is usually the main step of the therapeutic
      approach. The results of a retrospective analysis of a series of 381 patients
      treated from 1977 to 1990 for an inoperable NSCLC are reported. PATIENTS AND
      METHODS: Three hundred and twenty two men and 59 women were included into the
      study. Their mean age was 66 years. A squamous cell carcinoma was observed in 276
      cases (72%). A superior vena cava syndrome or a Pancoast's syndrome were present
      in 21 and 26 patients, respectively. Fifty-two per cent of the patients had a WHO
      performance status > or = 2. According to the TNM classification, the tumor
      distribution was as follows: 11 T1, 153 T2, 175 T3, and 42 T4. The mediastinum
      was involved in 174 patients. All patients were treated by external radiation
      therapy with a total dose of 60-65 Gy. Classical fractionation of the irradiation
      dose was done in 217 patients and hypofractionation was used for 164 patients.
      RESULTS: After treatment, improvement of the superior vena and Pancoast's
      syndromes was observed in 90% of the patients. Radiological complete response was
      obtained in 177 patients (47%). The 5-year overall survival rate was 6.2%. No
      significant differences in survival according to the initial tumor size, the
      mediastinum status or the fractionation scheme were noted. The 5-year survival
      rate was 13% in patients with a tumor that completely responded to irradiation.
      Death was mainly due to local failure (231 patients, 69%) and metastatic disease
      (107 patients, 32%). The radiotherapy tolerance was acceptable. CONCLUSION:
      Although irradiation provides good palliation and a 10%-survival rate at 3 years,
      the results relating to radiation therapy were disappointing.

PMID- 9273184
TI  - [Postoperative radiotherapy in non-small cell lung cancer. Apropos of a series of
      374 cases].
AB  - PURPOSE: Several randomized trials have led us to address the usefulness of post
      surgical external beam therapy (EBT) in non-oat cell bronchial carcinoma. Results
      that were obtained in a group of 374 patients submitted between 1977 and 1994 to
      identical therapy-the follow-up being done by the same team-and results of six
      randomized trials are analyzed. PATIENTS AND METHODS: The tumor stages were the
      following: T1, 13%; T2, 56%; T3, 29%; and T4, 2%; N0, 31%; N1, 34%; and N2, 35%.
      There were 85% histologically complete resections. EBT was administered according
      to either the classical irradiation scheme (C) or as an 'equivalent
      hypofractionated dose' (H) in the case of complete resection. When resection was
      not complete, 60 to 65 Gy were administered according to a C or an H irradiation
      scheme. The irradiation scheme was C in 73% of the cases and H in 27%. The EBT
      technique has been chosen to ensure maximum lung sparing. Following a 45 Gy
      irradiation with anteroposterior beams, orthogonal or, when necessary, oblique
      beams were used. Non homogeneity of the lungs was taken into account in
      establishing the treatment planning. The treatment file was collectively checked
      by the medical staff in 75% of the cases. EBT was indicated for N+(N1+N2), T3 and
      incomplete resections. RESULTS: The overall survival was 42% at 5 years and 27%
      at 10 years. The 5-year survival was 52% for stage I cancer (T1N0-T2N0), 60% for
      stage II cancer (T1N1-T2N1), 31% for stage IIIa cancer (T3N0, T1-3N2), 45% for
      complete resection and 30% when resection was not complete. CONCLUSION: Regarding
      the benefits of post-surgical radiotherapy, the analysis of the six randomized
      trials does not allow any conclusion. This might be due to either the
      insufficient number of cases, a follow-up time not long enough, incorrect
      radiotherapy, or insufficient available data. Comparison of the results
      pertaining to the six trials with those of our series shows an advantage for the
      current series, indicating that survival is likely to be improved if EBT is
      correctly done with regard to the dose, volume and technique used.

PMID- 9273185
TI  - [Concomitant radiochemotherapy in inoperable non-small cell lung cancer].
AB  - PURPOSE: As locally advanced and inoperable non-small cell lung cancers still
      have a poor prognosis, the present phase II study focused on the administration
      of concomitant chemotherapy and radiotherapy and was aimed at increasing both
      local and metastatic controls. MATERIALS AND METHODS: Thirty-nine patients (36
      male and three female patients, mean age, 56 years) were included into the study.
      Ninety five percent of them had a good performance status (OMS status 0 or 1).
      The histopathological analysis showed the existence of squamous cell in 64% of
      the cases. There was one stage I tumor, nine stage IIIA tumors and 24 stage IIIB
      tumors. In two cases, the tumor stage was unknown. The duration of each cycle of
      the protocol was 3 weeks and included the administration of cisplatin (50 mg/m2
      at d1 and d2) and fluorouracil (5-FU) (1 gr/m2 in continuous infusion at d1, d2,
      and d3), and external beam irradiation (20 Gy subdivided into 2 Gy-fractions that
      were administered from d1 to d12); the 3rd week was a resting period. RESULTS:
      The tolerance to the treatment was good. Fifteen per cent grade 3-4 leucopenia,
      3% grade 3-4 thrombopenia and 15% grade 3-4 nausea with vomiting were observed.
      No serious esophagitis was recorded. Chemotherapy was completed in more than 90%
      of the cycles. An objective response was described in 56% of the cases, with only
      3% of complete responses. However, evaluation was done on average 6 weeks after
      radiotherapy, at a time where post-irradiation fibrosis could hamper radiological
      assessment. Median survival and 2- and 3-year survivals were 11.4 months, 27% and
      14%, respectively. The only significant prognostic factor was the OMS performance
      status index, while the radiological response was particularly non-predictive of
      survival. Failure patterns were analyzed in 20 patients and consisted of the
      following: local relapse only, six cases; metastatic relapse only, 13 cases; both
      local and metastatic relapse, one case. CONCLUSION: The concomitant
      administration of 5-FU, cisplatin and external irradiation seems feasible in
      current clinical practice. Survival but not radiological response should be the
      only criteria to evaluate this type of association. Improvement in local control
      is not unlikely with this type of association.

PMID- 9273187
TI  - [Discussion on the role of radiotherapy in non-small cell lung cancer apropos of
      137 non-metastatic cases].
AB  - PURPOSE: Retrospective analysis of 137 patients with limited stage small cell
      lung carcinoma who received radiotherapy between 1978 and 1990 and literature
      review. MATERIALS AND METHODS: The population was divided into two groups
      according to the total dose of radiation delivered to the thorax: 45 Gy (1.8 Gy
      by fraction) or the equivalent irradiation dose administered by hypofractionation
      (group 1, 29 patients) and 65 Gy (1,8 Gy by fraction) or the equivalent
      irradiation dose administered by hypofractionation (group 2, 96 patients).
      RESULTS: The actuarial survival rate was 20% at 2 years and 9% at 5 years. It was
      25% at 2 years and 17% at 5 years for 12 patients with surgical resection. For
      patients who did not undergo surgical resection, it was 20% at 2 years and 9% at
      5 years for 96 patients belonging to group 2, while it was 14% at 2 years and
      3.5% at 5 years for group 1. Deaths due to local relapse reached 48% in the group
      treated with 45 Gy and 33% in the group treated with 65 Gy (NS). For the 33
      patients who were more than 70 years old at the time of treatment, the actuarial
      survival rate was 18% at 2 years and 6% at 5 years with death from other causes
      twice as high as that of patients who were less than 70 years old at the time of
      treatment. For the 59 patients who were less than 70 years old at the time of
      treatment, in whom supraclavicular node, pleural effusion or superior vena cava
      syndrome were not depicted and who were treated with the highest dose (4% of the
      total number of patients), the actuarial survival rate was 20% at 2 years and 14%
      at 5 years. Literature analysis shows that treatment of limited small cell lung
      cancer with chemotherapy and thoracic irradiation increased the overall survival
      rate from 16.5% to 23% at 2 years and the local control from 23% to 48%, in
      comparison with chemotherapy alone. CONCLUSION: Although these results are
      modest, they seem to be improved with more effective chemotherapy, especially
      with the association of radiotherapy and concomitant chemotherapy.

PMID- 9273186
TI  - [Optimization of combined radiotherapy and chemotherapy in treatment of non-small
      cell lung carcinoma].
AB  - PURPOSE: To report the results of CEBI 140 and 142 trials. These trials were
      aimed at improving the local control in stage III non-small cell carcinoma with
      concomitant chemotherapy and radiotherapy in the CEBI 140 trial, and with
      concomitant chemotherapy and radiotherapy followed by local excision in the CEBI
      142 trial. MATERIAL AND METHODS: Thirty-four patients presenting with stage III
      non-small cell lung carcinoma were included into the CEBI 140 trial from December
      1989 to December 1992. Patients were treated with a combination of daily
      cisplatin (6 mg/m2 per day, 144 mg/m2 in total), vindesine once a week (2.5
      mg/m2, 15 mg/m2 in total) and bifractionated radiotherapy (60 Gy/48 fractions/6
      weeks) followed by two cycles of cisplatin 120 mg/m2 (at d18 and d45 after
      completion of radiochemotherapy) and three cycles of vindesine (6 mg/m2 at d24,
      d31, and d38 after completion of radiochemotherapy). Twenty-eight patients
      presenting with stage IIIB non-small cell carcinoma-were included into the CEBI
      142 trial since January 1993. Patients received a combination of cisplatin (100
      mg/m2 at d1 and d24, 200 mg/m2 in total), vinblastine (4 mg/m2 at d1 and d24, 8
      mg/m2 in total), 5-fluorouracil in continuous infusion (1,000 mg/m2 from d1 to
      d3, and from d24 to 26, 6,000 mg/m2 in total) and bifractionated radiotherapy
      (two series of 21 Gy/14 fractions/9 days, 11 days apart) followed by a new
      evaluation and surgical excision. RESULTS: In the CEBI 140 trial, all patients
      received a complete course of radiotherapy, but the dose of cisplatin was
      decreased in 27% of the cases, and the dose of vindesine in 88%. There were two
      toxicity-related deaths. Three months after completion of the protocol, there
      were 50% of complete responders. The overall survival rates at 1, 2 and 3 years
      were 53, 33, and 11%, respectively, and disease-free survival rates 21 11, and
      11%, respectively. In the CEBI 142 trial the immediate tolerance was good. Twenty
      one patients (75%) underwent surgical resection. Four tumors could not be
      resected. Resection was histologically incomplete in one case, and complete in
      the 16 remaining cases. With a median follow-up of 14 months, ten patients were
      alive and disease-free. CONCLUSION: Preliminary results of the CEBI 142 trial are
      encouraging. More patients and longer follow-up are needed for definitive
      conclusion. It would be of interest to implement a randomized trial comparing the
      CEBI 142 scheme and classical radiation therapy.

PMID- 9273188
TI  - [Endobronchial brachytherapy: the Saint-Louis Hospital experience].
AB  - PURPOSE: During the evolution of lung cancer, bronchial obstruction is often
      noticed and is sometimes responsible for serious symptoms. Several methods of
      desobstruction can be proposed, including brachytherapy. MATERIALS AND METHODS:
      One hundred forty-nine patients presenting with endobronchial brachytherapy were
      included into the study. Seventy-three were treated with curative intent, 47 with
      palliative intent and 29 with a combination of external irradiation and
      brachytherapy. We usually delivered a series of two 7-Gy fractions (1 cm from the
      catheter), the treatment being repeated one, two or three times. RESULTS: When
      all symptoms were taken into account, respiratory function improvement was
      present in 79% of the patients. Among the 132 tumors that could be evaluated via
      a new endoscopy 2 months after treatment, 64 (48.5%) were in complete
      histological remission. The median survival was 14.4 months for the patients
      treated with curative intent. Eleven massive hemoptysies and 13 radiation
      bronchitis were observed. CONCLUSION: These results confirm the feasibility and
      good results related to endobronchial brachytherapy, though controlled studies
      are needed to better define its place in the therapeutic strategy of bronchial
      carcinomas.

PMID- 9273189
TI  - [Place of radical surgery in the treatment of non-small cell lung cancer. Apropos
      of 969 cases].
AB  - PURPOSE: Retrospective analysis of the results of radical surgery in a series of
      969 patients presenting with non-small cell lung cancer. PATIENTS AND METHODS:
      From April 1984 to December 1981, 969 patients underwent radical surgery with
      mediastinal node dissection for non-small cell lung cancer. Surgery included 507
      pneumonectomies, 447 lobectomies and 15 segmentectomies (for patients suffering
      from respiratory failure). RESULTS: The rate of intrahospital mortality was 4.3%.
      The rate of crude survival at 5-years was 45.8%. The tumor size (P = 0.004) and
      visceral pleura ruptures (P = 0.01) were significantly correlated to the 5-year
      survival rate that was reaching 56% for patients with no demonstrable metastasis
      to regional lymph nodes (NO), 46.6% for patients with metastasis to lymph nodes
      in the peribronchial or the ipsilateral hilar region (N1), and 20.8% for patients
      with metastasis to the ipsilateral mediastinal and subcarinal lymph nodes (N2) (P
      = 0.001). In case of stage N2 cancer, the 5-year survival rate was 28.7% when
      only one anatomical level was involved, and 8.7% when more than one anatomical
      level was involved (P < 0.0001). CONCLUSION: The main prognostic factor was nodal
      involvement.

PMID- 9273190
TI  - [A combined radiochemotherapy trial for non-small cell lung cancers: initial
      results].
AB  - PURPOSE: Analysis of the preliminary results of a phase I study investigating the
      feasibility of concomitant chemotherapy with daily doses of carboplatin (20 to 25
      mg/m2/d over 45 or 10 min) and accelerated chest irradiation (60 to 64 Gy over 4
      weeks, 2 Gy per fraction, using the concomitant boost technique). MATERIALS AND
      METHODS: This combination was given alone or following three cycles of induction
      chemotherapy (cisplatin, 25 mg/m2 per day from d1 to d5; 5-fluorouracil, 600
      mg/m2 per day from d1 to d5 and vinorelbine, 25 mg/m2 per day at d1 and d5 with a
      4-week interval) in 15 patients with locally advanced unresectable non-small cell
      lung cancer. All patients received the planned sequence. RESULTS: The dose
      limiting toxicity was esophagitis (5 out of 15 grade 4). No toxic deaths were
      observed. The tumor response rate was high: six out of 15 complete responses and
      14 out of 15 tumor regressions greater than 50%. The median survival was not
      reached after a mean follow-up of 14 months (range, 6-28 months). CONCLUSION: We
      are now planning a multicenter phase II study using the following combination: 20
      mg/m2 of daily carboplatin over 10 min and a 60-Gy irradiation dose over 4 weeks.

PMID- 9273191
TI  - [Computerized tomography-guided needle biopsy for the diagnosis of pulmonary
      nodules: analysis of a series of 41 patients].
AB  - This study was aimed at assessing percutaneous biopsy under computerized
      tomography (CT) guidance, its results in terms of diagnostic value, factors
      contributing to its complications or success, and its indications. Results
      obtained from a series of 41 patients and data from previous clinical trials were
      compared. Patients who were not eligible due to either poor physical condition or
      a tumor that could not be reached were not included into the study. Various
      factors, ie, the tumor location, the size of the lesion, the distance between the
      lesion and the thoracic wall, and the type (histological and/or cytological) of
      samples, were analyzed. Results were evaluated according to the disease evolution
      or pathological findings. Tumoral cells were found in 23 samples. Eighteen
      samples were negative for malignancy, with eight benign lesions and ten false
      negative. Complications that occurred just after the biopsy were recorded.
      Failures and complication factors were analyzed and compared to those already
      described. CT-guided needle biopsy is an admitted alternative to thoracotomy,
      even for small nodules deeply located. The use of this technique should be
      discussed when fiberoptic endoscopy leads to negative results. Various tumors
      cannot be reached using CT-guided needle biopsy and this technique is more
      efficacious for bulky nodules. The thickness of lung parenchyma passed through
      does not seem to change the risk of pneumothorax. The use of laser guidance might
      help locate the tumor with more accuracy.

PMID- 9273192
TI  - [Videothoracoscopy in the spreading evaluation of bronchogenic cancers].
AB  - Mediastinoscopy is often necessary in management of lung cancer. Progress
      recently achieved in the field of thoracoscopy has led us to introduce
      videothoracoscopy as a complement to mediastinoscopy in preoperative management
      of such tumors. From June 1994 to June 1995, 113 patients presenting with stage I
      IIIA lung cancer underwent a videothoracoscopy before surgery. No side-effects
      were observed. Results obtained in this study lead us to conclude that
      videothoracoscopy is useful before surgery of lung cancer.

PMID- 9273194
TI  - Proceedings of the International Symposium on Molecular Mechanisms of Myofibril
      Assembly. Chiba, Japan, November 7-9, 1996.

PMID- 9273193
TI  - [Radiation tolerance of patients after pneumonectomy for bronchial cancer: role
      of pulmonary function tests].
AB  - Radiation is often necessary after pneumonectomy, either immediately or due to
      local cancer recurrence. High radiation doses represent a challenge due to the
      limited tolerance of the lung and the necessity of preserving and protecting the
      remaining lung parenchyma. The use of CT scan based-treatment planning allows
      delivery of high radiation doses. To evaluate the radiation tolerance of the lung
      after high radiation dose, we compared pulmonary function tests performed before
      surgery and after radiation therapy. Ten male patients (mean age, 56 years old;
      age range, 45-73) were irradiated after pneumonectomy for lung cancer. All
      patients had a CT scan-based treatment planning. The mean radiation dose was 56
      Gy (45-66 Gy) delivered with a linear accelerator and multiple complex fields.
      Two or more sets of pulmonary function tests were available (before surgery and 2
      to 6 months after radiation). No patient developed clinical radiation pneumonitis
      and most of the patients had a minimal paramediastinal fibrosis at CT scan.
      Postirradiation pulmonary lung tests were compared to the theoretical values of
      the estimated defect observed after pneumonectomy. No significant decrease in
      forced expiratory volume in 1 s/inspiratory vital capacity (FEV1/IVC) was
      observed in ten evaluable patients; the observed values were comparable to those
      expected after pneumonectomy without irradiation (FEV1/IVC: 61 to 100%), showing
      that irradiation did not alter pulmonary function. Computerized tomography-based
      treatment planning and the use of complex beam positioning allowed optimal lung
      parenchymal preservation. Through this procedure, high doses of radiation can be
      delivered to the mediastinum and bed tumor. Comparison of pulmonary function
      tests performed before surgery and after radiation showed no alteration of lung
      function, even after high doses. Optimal tools required for the evaluation of
      radiation on lung parenchyma are still to be defined.

PMID- 9273195
TI  - [Opinions about disease among members of the social network of patients with
      Hansen's disease in Recife].
AB  - This article describes a study done in Recife, Brazil, between November 1993 and
      July 1994 to explore the opinions of the members of the social network (for
      example, family members, friends, and neighbors) of carriers of Hansen's disease
      regarding their estimation, interpretation, and management of physical
      manifestations of the disease in the time leading up to diagnosis. The sample
      consisted of 93 members of the social network, ranging in age between 20 and 70
      years, who supported the course of action of 83 patients diagnosed in the study
      period. The analysis sought to detect differing capacities among the members of
      the patients' social network to discriminate between persons classified as cases
      (presence of disabilities or precursor lesions) or controls. The study found a
      lack of information about transmission of Hansen's disease and revealed a
      transitional phase in which there was expectation of cure along with a
      stigmatizing view of the consequences of the disease. Only one-quarter of the
      study subjects suspected prior to diagnosis that the patient had Hansen's
      disease, which suggests low perception of the risk represented by the disease and
      reinforces the idea that its physical manifestations can be invisible. The
      results reveal a profile of perception and management of Hansen's disease that
      favors its propagation and the development or worsening of its physical and
      social consequences.

PMID- 9273196
TI  - [Auditory provoked potentials in children with neonatal risk for hypoacusia].
AB  - Auditory evoked potentials of the brain stem (AEPBS) provide a simple noninvasive
      method of evaluating hearing function and have been widely used for early
      detection of hypoacusis in children. Between April 1992 and May 1994, a study was
      done of 400 Mexican children who presented at least one neonatal risk factor for
      hearing impairment. The average age of the children studied was 6.6 months and
      their average gestational age at birth was 35.1 weeks. Just over half of them
      (51%) had been treated with amikacin. The study found 1427 risk factors (3.5 per
      child), the most common ones being exposure to ototoxic substances,
      hyperbilirubinemia, and birthweight of less that 1500 g. In 27% of the children,
      peripheral auditory changes were found, and 13% did not respond to auditory
      stimuli. Low birthweight and young gestational age at birth, high serum
      concentration of bilirubin, sepsis, subependymal or intraventricular hemorrhage,
      mechanical ventilation, and exposure to ototoxic substances were significantly
      associated with the presence of severe or profound hypoacusis.

PMID- 9273197
TI  - [Evaluation of beta-cypermethrin for the control of Triatoma infestans].
AB  - This study assessed the insecticidal effect in the laboratory and in the field of
      the new pyrethroid beta-cypermethrin against Triatoma infestans, the vector of
      Chagas disease, and compared it with that of deltamethrin. Comparison of the 50%
      lethal dosis (LD50) of both pyrethroids showed that beta-cypermethrin is more
      effective against the nymphs and that deltamethrin is more effective against the
      adults. Evaluation of the 50% lethal concentration (LC50) of the flowable
      formulations of both insecticides, placed on different surfaces, showed that
      their effectiveness on glass is similar, while on a ceramic surface deltamethrin
      is slightly more effective. The flowable formulations of the two insecticides
      were tested in 100 infested homes in the province of Santiago del Estero,
      Argentina. Deltamethrin was applied at a surface concentration of 25 mg/m2 and
      beta-cypermethrin at 50 mg/m2. The real surface concentrations of these products
      were analyzed from filter paper samples placed on walls and ceilings. Gas
      chromatography revealed good agreement with the target concentrations. In
      addition, entomological assessments were carried out 60, 90, 180, and 365 days
      after the treatments. Infestations were found only during the last assessment: in
      the peridomiciliary area of 10% of the houses treated with beta-cypermethrin and
      in 7% of the houses treated with deltamethrin (6% in the peridomiciliary area and
      1% inside the house). The results indicate that beta-cypermethrin's effectiveness
      in controlling T. infestans when applied at a concentration of 50 mg/m2 is
      similar to that of deltamethrin applied at a concentration of 25 mg/m2.

PMID- 9273198
TI  - [Hospital quality assurance programs].

PMID- 9273199
TI  - [Violence and health in Colombia].
AB  - In Colombia, violence seems uncontrollable. Along with massacres and group
      killings of astonishing cruelty, there are also kidnappings and disappearances,
      abuse of children and the elderly, and rape of young adolescents. Every day,
      without respite, Columbians are witnesses or victims of street crimes as well as
      racial, sexual, and socioeconomic discrimination. Unwillingly, they become agents
      of aggression in public transport, at home, at school, and at work. Colombia has
      the highest rates of mortality from homicide in the world. Apart from the
      enormous institutional burden that violence imposes on the health services and
      forensic medicine, it now constitutes the principal public health problem in the
      country. To confront it, the health sector must develop policies and finance
      actions, develop innovative ways to train personnel, implement public education
      processes, and devote more effort and greater creativity to research, which up to
      now has provided some, but not enough, important answers. Violence, which is the
      substitution of force for any type of dialogue, must be considered within the
      context of life and health. This it not merely an attempt to rationalize
      violence, much less to substitute words or reflection for action, but rather an
      attempt to understand it in depth in order to search for alternatives. With that
      goal, this article analyzes the subject of violence in Colombia, principally from
      the perspective of its effect on the health of the citizens and its implications
      for the health sector. The author fully recognizes the subjectivity and
      limitations of the views he expresses herein.

PMID- 9273200
TI  - [Contemporary views of pharmacologic treatment for congestive heart failure].

PMID- 9273201
TI  - [The effect of sotalol hydrochloride therapy on atrial signal-averaged ECG in
      patients with paroxysmal atrial fibrillation].
AB  - The aim of this study was to evaluate of oral sotalol hydrochloride effects on
      atrial signal-averaged ECG (ASAECG) during time- and frequency-domain analysis in
      patients with paroxysmal atrial fibrillation (PAF) during ischemic heart disease
      (IHD). The study population of 27 was composed of 16 female and 11 male, mean age
      56.1 +/- 8.4. The dose of oral sotalol was 160 mg/day for all days. Recording of
      ASAECG and 24-hours Holter monitoring were made at baseline, after 10 days and
      after 6 weeks of sotalol therapy. For ASAECG were calculated time-domain
      parameters: the root mean square voltage of the signals in the last 10, 20, 30 ms
      of the filtered P-wave (RMS 10, 20, 30) and total time duration of filtered P
      wave (PWD) and time duration of P-wave for Frank leads X, Y, Z (XP, YP, ZP).
      During frequency-domain analysis of the terminal part of P-wave we calculated the
      following parameters in range from 40 Hz to 400 Hz: energy spectrum > -60 dB (A)
      and decibel drop at 40 Hz (Dd) in logarithmic scale and area ratio 20-50/0-20 Hz
      (Ar), magnitude ratio (MR1-7) in linear scale for a vector magnitude.
      Supraventriculat arrhythmias were estimated quantitatively and qualitatively
      during Holter monitoring. The following parameters were estimated in a case of
      PAF recording: time of manifestation, duration, number of PAF episodes per day,
      mean heart rate during PAF and subjective symptoms. Moreover, comparable analysis
      of the following parameters: dimension of left atrial, age, gender, time duration
      of IHD and PAF and wall motion disturbances-hypokinesis and also left ventricular
      ejection fraction, mitral regurgitation was done between patients with effective
      and no effective of antiarrhythmic therapy. Our observation have indicated that
      oral sotalol therapy are responsible for statistically significant decrease of
      total time duration of filtered P-wave (PWD) and time duration of P-wave for
      Frank leads X, Y, Z (XP, YP, ZP) and increase area ratio 20-50/0-20 Hz in
      patients with PAF during IHD. Moreover, comparable analysis of above-mentioned
      parameters have not showed statistically significant differences between examined
      patients with effective and lack of effective sotalol therapy.

PMID- 9273202
TI  - [Prevalence of thrombosis in secondary antiphospholipid-protein syndrome].
AB  - Antiphospholipid-protein syndrome (APS) comprises venous and arterial thrombosis,
      spontaneous abortion and thrombocytopenia in patients with antiphospholipid
      protein antibodies (APA). Such antibodies are detected by immunoenzymatic (ELISA)
      methods (e.g. anticardiolipin antibodies-ACL) or coagulation assays (lupus
      anticoagulant-LA). APS in patients showing other symptoms of autoimmune disease
      is called secondary antiphospholipid-protein syndrome. The aim of the study was
      to find relation between history of thrombosis and APA in a group of patients
      with lupus erythematosus and lupus-like disease. Lupus anticoagulant was detected
      by a three step procedure using phospholipid dependent clotting assays and
      anticardiolipin antibodies were measured by ELISA. We studied 95 subjects (91
      women, 4 men) suffering from lupus erythematosus (67 patients) and lupus-like
      disease (28 patients). Lupus anticoagulant was found in 26, anticardiolipin
      antibodies IgG in 34 and IgM in 27 subjects. In a retrospective study 40
      thrombotic events were detected in 36 patients; deep vein thrombosis in 19,
      pulmonary embolism in 7, ischaemic CNS events in 13 and myocardial infarction in
      one. Thrombosis was present more often in subjects with LA (61%) and ACL IgG
      (52%) than in subjects without these antibodies (24%) (p = 0.004 and 0.015,
      respectively). ACL IgM antibodies were not related to thrombotic episodes. The
      ACL IgG antibodies and LA are helpful in identifying subjects at risk factors of
      venous and arterial thrombosis among patients suffering from lupus erythematosus
      and lupus-like disease.

PMID- 9273203
TI  - [Pulmonary function tests and bronchial reactiveness with histamine in patients
      with atopic dermatitis and bronchial asthma].
AB  - Atopic dermatitis and bronchial asthma are genetically dependent diseases,
      connected with an over-synthesis of IgE antibodies, in which a chronic
      inflammation is characteristic for their pathogenesis. The coincidence of
      bronchial hyperresponsiveness and symptoms of atopic dermatitis suggests to
      investigate the degree of bronchial reactions in atopic dermatitis or asthma
      patients. The main goal of this analysis was to compare the pulmonary functional
      tests and the bronchial histamine induced reactiveness in 71 patients. The
      investigation included 27 atopic dermatitis patients, 12 asthma-prurigo patients
      and 32 bronchial asthma patients. All of them were tested with "Pneumoscreen"
      (Jaeger), in order to define: VC, FEV1, FEF50, and Raw. The bronchial
      reactiveness with 1% histamine solution, was tested on "Bronchoscreen" (Jaeger).
      In atopic dermatitis and asthma-prurigo patients, no obstructive ventilation
      impairment was found. The bronchial hyper-reactiveness to histamine was found in
      11.1% of atopic dermatitis patients, 16.7% of asthma-prurigo patients and 78.1%
      of bronchial asthma patients. The coexistence of bronchial asthma and atopic
      dermatitis increases the degree of bronchial reactiveness.

PMID- 9273204
TI  - [Ketone bodies in patients after partially liver resection].
AB  - This study explores the relationship between Arterial Ketone Body Ratio (AKBR =
      acetoacetate/3-hydroxybutyrate) and the patients state after partially liver
      resections. Enzymatic methods of Mellanby and Williamson for the determination of
      ketone bodies (acetoacetate and 3-hydroxybutyrate) were used. Twelve surgical
      patients (8 women and 4 men) were examined. The control group consisted of 5
      persons. Ketone bodies were measured in samples of arterial blood taken before
      operation and in the postoperative period. Then AKBR values were calculated.
      Patients were classified into three groups. Group A patients (8 subjects) had
      AKBR value higher than 0.7, group B patients had AKBR between 0.4 and 0.7 (2
      cases), and group C patients had AKBR below 0.4 (2 cases). We observed that
      incidence of postoperative complications increased with the decrease of AKBR
      value. No postoperative complications and good general conditions of patients
      were observed in group A only. Group B patients had postoperative complications,
      whereas group C patients decreased in the postoperative period. These results
      indicate that Arterial Ketone Body Ratio is a good indicator for prognosis of
      postoperative survival of patients after partially liver resections.

PMID- 9273205
TI  - [Measurement of bone structure on the radiograph. Utopia or reality?].
AB  - A method of computerised analysis of bone structure assessment using a
      professional image analyser is described. Analyses of experimental radiographs of
      human radius taken over a period of time in a standard laboratory were performed.
      The radiographic technique was ascertained as the main source of a precision
      error. The reproducibility of the analysis using the method described was found
      to hold a limited range of error. The program Quantitrab makes possible a
      quantitative description of the bone structure parameters on the radiograph.

PMID- 9273206
TI  - [Differences in the morphology of gastric and duodenal ulcers in a twenty-five
      year period from 1976-1990].

PMID- 9273207
TI  - [Coexpression of CD4 and CD8 antigens and the appearance of HLA-DR and CD25
      receptors on lymphocytes as markers of immune activation in patients with HIV
      infection].
AB  - Results of quantitative determinations of peripheral blood lymphocytes presenting
      CD4 or simultaneously CD4 and CD8 antigens as well as HLA-DR and CD25 antigens in
      patients with different clinical stages of CD4+ and CD4+CD8+ cells were observed.
      The fall of CD4+CD8+ lymphocytes percentage was slight in the initial stages of
      infection but more sharp during the full-blown AIDS. The percentage of HLA-DR
      positive cells was higher in seropositive patients in comparison with controls
      and increased with the progression of HIV infection into AIDS. The CD25
      expression was also higher in HIV-infected patients, however, it decreased in
      patients with late stages of AIDS. The observed disturbances could be caused by
      the direct destruction by replicating HIV or by severe abnormalities of immune
      system function.

PMID- 9273208
TI  - [A trial of treatment with thymus factor (TFX) for chronic autoimmune hemolytic
      anemias].
AB  - 30 days treatment TFX was performed in 8 cases AIHA (autoimmune hemolytic anemia)
      with presence of warm antibodies refractory after routine treatment
      (glucocorticosteroids, azathioprine, splenectomy): After TFX treatment in 2 cases
      autoantibodies were not detectable, in 5 cases reaction DAT (direct antiglobulin
      test) was decreased. Eluate antibody level and serum antibody level were
      decreased, too. Decreasing amount of red cells autoantibodies was confirmed by
      enzyme-linked antiglobulin test (ELAT) in 2 cases. Autoantibody level measured by
      semiquantitative and quantitative methods did not increase in any other case.
      Adverse effects of TFX treatment were not observed.

PMID- 9273209
TI  - [Treatment of anemia in patients after long term hemodialysis with human
      recombinant erythropoietin].
AB  - Clinical effectiveness of recombinant human erythropoietin (Epo) administered
      subcutaneously (sc) was examined in 19 anemic patients. The patients were given
      Epo twice weekly 2000 U (67 +/- 12 U/kg/week). The results were compared to the
      group of 20 patients receiving Epo intravenously (i.v.) in doses from 156 +/- 57
      U/kg/week to 205 +/- 105 U/kg/week, thrice weekly (control group). According to
      our findings the target hematocrit level was reached within 12.4 +/- 10 weeks in
      patients treated sc and 9.6 +/- 5.8 weeks in the control group. The Epo dose
      required to achieve the increase of Hb by 1 g% was 534 +/- 347 U/kg in patients
      treated sc and 973 +/- 534 U/kg in the control group. Achievement to target level
      of hematocrit required lower total amount of Epo units in patients receiving Epo
      sc (844 +/- 754 vs 1958 +/- 1496 U/kg). Cost of treatment of 1 patient taking Epo
      sc was significantly lower. The decreasing of frequency of Epo administration was
      utilized in 17 patients, from twice weekly to once weekly 400 U. After 6 months
      of the treatment Hb remained unchanged. We conclude that subcutaneous
      administration of Epo, once weekly is an efficient and convenient method of
      treatment of renal anemia.

PMID- 9273210
TI  - [Analysis of clinical symptoms of renal clear cell carcinoma].
AB  - An analysis of the clinical symptoms has been carried out in the group of 110
      patients who underwent nephrectomy for a clear-cell carcinoma. Total hematuria
      (47.3% of patients) has been a predominant symptom of the tumour. Pain felt in
      the back has been noted in 39.1% of patients. Palpable tumour has been noted in
      34.5% of patients. Such symptoms have been present simultaneously (Israel's
      triad) in 12.3% of patients. Tumour has been diagnosed accidentally, mainly with
      USG, in 37.3% of patients. It has been found that classic clinical symptoms of
      this cancer are nowadays less frequent than before introducing ultrasound
      examination.

PMID- 9273211
TI  - [Morphologic analysis of congenital central nervous system malformations in
      children from the first of life dying in the years 1986-1990].
AB  - An incidence and morphology of the CNS congenital malformations in newborn babies
      and infants were analysed in the consecutive autopsies carried out in 1986-1990,
      i.e. following Tscharnobyl disaster. The obtained results were compared to those
      seen in the two earlier periods (1976-1980 and 1981-1986). In 1986-1990, a
      percentage of autopsies showing congenital CNS malformations increased
      approximately by two-fold (15%). The highest percentage of such malformations in
      specific years of the analysed period was noted in 1990 (20%). Central nervous
      system malformations were more frequent in female sex (57%) than in male sex
      (43%). In 64% of cases newborn babies were affected. A percentage of CNS
      malformations coexisting with other congenital malformations increased to 40% in
      the analysed period of time (from 29.4% in 1976-1985). Meningomyelocele (41%),
      congenital hydrocephalus (21.5%), multiple anomalies in brain (14%), and
      anencephaly (12.6%) constituted the most frequent group of CNS malformations. In
      1986-1990, an incidence of meningomyelocele increased by more than two-fold (if
      this anomaly coexisted with hydrocephaly, an increase in the incidence exceeded
      three-fold), and hydrocephaly as well as an increase in the incidence of
      anencephaly by 1.5 times in comparison with 1976-1985.

PMID- 9273212
TI  - [Evaluation of the efficacy of anti-emetic therapy with ondansetron injected
      intravenously at a daily dose of 8mg (analysis of material)].
AB  - The one of the most unpleasant undesirable symptoms of chemotherapy are nausea
      and vomiting. Authors evaluated and efficacy of ondansetron in anti-emetic
      therapy in 217 patients. In they opinion is very effective and improves a quality
      of life.

PMID- 9273213
TI  - [Clinical evaluation of the isotonic solution of theophylline for intravenous
      injection].
AB  - The safety and tolerance of intravenous theophylline in asthmatic patients was
      investigated. The effect upon the lung function tests and frequency of cardiac
      arrhythmias were evaluated in 15 patients after five days treatment with
      theophylline 300 mg twice a day. Measurements of the peak expiratory flow (PEF)
      were obtained prior to theophylline administration, immediately after first
      intravenous infusion and 1.3 and 6 hours later and before and after second
      infusion, while serum theophylline levels were determined at the same time by
      enzyme immunoassay (Diagnostica Merc). The same measurements were made at the
      fifth day of observation. Continuous 24 hour Holter monitoring of the
      electrocardiogram before the study and at the fifth day of the treatment was
      performed. Biochemical investigations included aspartate and alanine
      aminotransferase (GGTPi GOT), sodium and potassium ion concentrations, serum
      levels of creatinine, glucose and bilirubin hematocrit, hemoglobin concentration,
      MCHC, red blood cells count and white blood cell differential count were
      determined. The therapeutic concentration of theophylline in serum were found in
      all subject treated with theophylline 300 mg twice a day. The improvement in lung
      function and no changes in cardiac rhythm were observed the biochemical findings
      did not demonstrate any significant differences after five days of the study. The
      study confirm safety and good tolerance of intravenous theophylline used in the
      doses 300 mg twice a day.

PMID- 9273215
TI  - [Neuro-fibro-liposarcoma healed by partial surgical intervention complicated by
      post-transfusional shock].

PMID- 9273214
TI  - [Evan's syndrome with antiphospholipid-protein antibodies].
AB  - This is a case report of a 34 years old man with Evans syndrome associated with
      antiphospholipid-protein antibodies. They include lupus anticoagulant and
      antibodies against cardiolipin, prothrombin and beta 2-glycoprotein I, detected
      by ELISA. No thrombotic events were observed. The presence of several antibodies
      directed against surface cell membrane structures in Evans syndrome suggests a
      common pathogenetic mechanism.

PMID- 9273216
TI  - [Spontaneous esophageal perforation--Boerhaave's syndrome].
AB  - Spontaneous perforation of the esophagus (Boerhaave's syndrome) is an emergency
      that requires early diagnosis if death or serious prolonged illness is to be
      averted. The literature is reviewed and the causes of delay in diagnosis are
      analyzed.

PMID- 9273217
TI  - [Atrial fibrillation. What's new in treatment and prophylaxis of embolic
      complications?].
AB  - Atrial fibrillation in people over 70 years old increase to 2-4% of a population.
      Atrial fibrillation is often complicated by. Authors discussed some new views of
      contemporary treatment and prophylactic.

PMID- 9273218
TI  - [Tissue spectroscopy. New generation of optical methods for cancer detection].
AB  - Recent developments in the field of new, non-invasive, sensitive methods of
      cancer detection based on measurements of autofluorescence of cells are
      discussed. Research oriented on a detection of human cancer has been carried on
      by several groups for last six years only but has already yielded important data
      pointing to a possibility of both in situ and in vitro detection of cancerous
      tissues in several human organs, especially lung, gynecological tract, skin and
      gastro-intestinal tract. At least two such methods have been currently subject to
      clinical tests.

PMID- 9273219
TI  - [Laboratory diagnosis of lupus anticoagulant].
AB  - Lupus anticoagulant (LA) prolongs clotting times in vitro, but in vivo leads to
      an increased risk of thromboembolic complications. LA is detected in many
      patients with lupus erythematosus but also in subjects without any autoimmune
      disease (primary antiphospholipid syndrome). We determined LA in 133 patients,
      mostly with lupus erythematosus and other autoimmune diseases. Three screening
      and two confirmatory tests based on different mechanisms of clotting system
      activation were used. LA was found in 34 patients. DRVVT was the most useful test
      in detecting LA while kaolin clotting time was the least sensitive.
      Anticardiolipin antibodies (ACL) of IgG class were found in 41 patients studied
      (31%). They were most often detected in patient positive for LA (64%). ACL IgM
      were not associated with prolonged clotting times. Laboratory diagnosis of
      antiphospholipid syndrome is easy when the presence of LA is confirmed by two
      independent tests and in addition ACL would be detected. In other cases, when
      only single tests are positive, it is suggested to repeat diagnostic procedure at
      least once.

PMID- 9273220
TI  - [Homeostasis of calcium in the organism].
AB  - Calcium is one of the essential ions necessary for normal functioning of the
      organism. The serum calcium concentration under physiological conditions is kept
      within narrow range between 2.25 to 2.65 mmol/l. This is possible using the
      complex interaction of various hormones: parathyroid hormone (PTH), active
      metabolites of vitamin D (primarily 1,25(OH)2D3) and calcitonin (CT). The three
      target organs are also involved in maintenance of calcium homeostasis: gut,
      kidney and bone. These are directly or indirectly the target organs of
      calciotropic hormones. The calcium metabolism and, therefore, calcium balance in
      the organism are dependent on many various factors such as: age, sex, nutritional
      condition, illnesses and prescribed medication.

PMID- 9273221
TI  - [Hypertension crises and their treatment].

PMID- 9273222
TI  - [Barlow's syndrome--personal studies].
AB  - Symptoms of Barlow's syndrome were analysed in 60 patients. The diagnosis is
      described as a plenty of disturbances in the circulatory system. Observed
      arrhythmias were often one of the important symptoms.

PMID- 9273223
TI  - [The influence of laser radiation on blood flow in patients with ischemia of the
      lower limbs (based on the analysis of the hyperemia reactive test)].
AB  - The aim of this paper was to assess the influence of low power infra red laser
      radiation on blood flow in patients with atherosclerotic disease of the lower
      limbs. The investigations were based on the hyperemic reactive test and the
      ankle/brachial pressure index. Analysis of the hyperemic reactive test allows to
      evaluate microcirculation mechanisms. The results obtained indicate that
      treatment of low power laser radiation allows to improve microcirculation
      mechanisms and blood flow in the lower limbs.

PMID- 9273224
TI  - [Clinical course and treatment of toxocariasis in children].
AB  - Toxocariasis is a parasitic disease. Larvae of Toxocara canis, as intra-tissular
      parasites, can survive in human organism for 10 years. Clinical symptoms depend
      on massiveness of infection, organ localisation and defensive reactions of
      patients. 74 children were observed (in age from 1 year 8 months to 15 years).
      70% of them had intraocular lesions which is the most serious complication of
      toxocariasis. Larva of T. canis is neurotropic. EEG revealed abnormalities in 73%
      of patients. The diagnosis of toxocariasis was confirmed by immunoenzymatic
      reaction ELISA with T. canis antigen. The patients were treated with hetrazan, if
      intraocular lesions were present prednisone was added. Improvement was achieved
      in 78% of children with intraocular lesions, in the rest effectiveness of the
      treatment is questionable.

PMID- 9273225
TI  - [Impact of active and passive smoking during pregnancy on birth weight of the
      newborn].
AB  - The purpose of the paper was to compare the effects of active and passive tobacco
      smoking during pregnancy on the birth weight of newborns and to validate self
      reported smoking habit against the plasma cotinine level. Investigations on birth
      weight have been carried out in the sample of 1165 schoolchildren. Data on
      tobacco smoke and the birth weight of children were collected by standardized
      interviews with mothers. It was disclosed that the effect of passive smoking in
      never smokers was weaker (weight reduction by 73.1 g) than that of active
      smoking. It was estimated that active tobacco smoking of 10 or more cigarettes
      per day is to reduce the birth weight by about 450 g. Both effects of active and
      passive smoking in pregnancy were statistically significant. When the self
      reported smoking status was compared with biochemical marker of exposure (plasma
      cotinine > 10 ng/ml) in 158 women at delivery, it became apparent a low
      sensitivity (43%) of the self-reported data on smoking, however, combined with
      high specificity (95%). It was shown that the exposure bias lead to a significant
      underestimation of association between low birth weight and tobacco smoking.

PMID- 9273226
TI  - [Interleukin-6 and interleukin-8 in bronchoalveolar lavage fluid material from
      patients with chronic bronchitis].
AB  - The aim of this study was evaluation of interleukin-6 (IL-6) and interleukin-8
      (IL-8) in creation of inflammation of lower airways in patients with chronic
      bronchitis. 32 patients with chronic bronchitis and 14 subjects of control group
      took part in this study. Spirometry (Jaeger eq.), bronchofibroscopy and
      bronchoalveolar lavage (Olympus eq.) were performed in every patient. Cytology
      and concentration of IL-6 and IL-8 (kits from R&D) were measured in 1 ml of
      lavage fluid recovered. The increased levels of IL-6 and IL-8 in BAL were
      correlated with clinical parameters. We conclude that these two cytokines
      participate in creation of inflammatory changes of lower respiratory tract in
      chronic bronchitis.

PMID- 9273227
TI  - [A quantitative study of the role of fibrinogen molecules in inter-red cell
      connections of patients with stroke taken from selected clinical groups].
AB  - In the group of 36 patients with acute ischemic stroke the study of the influence
      of arterial hypertension on the red cells and fibrinogen interaction was carried
      out in the aspect of the fibrinogen molecules contribution to this phenomenon,
      respecting the role of other plasma biochemical factors. Patients were divided
      into two clinical groups: with and without arterial hypertension. The
      quantitative fibrinogen molecules contribution to the inter-red cells connections
      in patients with arterial hypertension was lower than in the group without this
      accompanying disease (statistical significance was indicated for 80% and 60% of
      plasma dilution). The first group of patients was also characterized by a
      significant increase of IgA level (in comparison with the control group), whereas
      the red cells and fibrinogen interaction measured as a value of YSS was similar
      in both analyzed clinical groups.

PMID- 9273228
TI  - [The influence of noise increased arterial blood pressure in workers during the
      work day].
AB  - The arterial blood pressure was measured three times: before beginning of work on
      morning shift, after 3-4 hours of work, and after its completion in 2599 workers
      exposed to continuous or intermittent noise of over 90 dB intensity and in 2454
      controls. The rise of the systolic and diastolic pressure during the working day
      depended on the initial pressure level, age and duration of employment as well as
      the exposure to noise. Among these variables the effect of noise was most
      significant, and the importance of this factor increased with increasing duration
      of employment. In the group exposed to noise and in the controls the greatest
      rises of the systolic and diastolic pressure during working day were noted in
      workers with borderline hypertension, and were low in those with normal pressure.
      On the other hand, workers with systolic hypertension were most prone to
      diastolic pressure rise. A reverse observation was made in workers with diastolic
      hypertension. In all groups exposure to noise increased the pressor reaction.

PMID- 9273229
TI  - [The influence of recombinant human erythropoietin on platelet phospholipid fatty
      acid composition in patients on long term hemodialysis].
AB  - The disturbances of blood platelet activity play an important role in the
      formation of haemostasis disorders in patients with end-stage renal failure
      (ESRF). Phospholipids and their fatty acids play an essential role in the
      structure and function of the platelet. In patients with ESRF, changed lipid
      metabolism and also changed platelet phospholipid composition are observed. Data
      is available on the positive influence of recombinant human erythropoietin
      (rHuEPO) on some lipid metabolism disorders in patients with ESRF. The aim of
      this study was to demonstrate the influence of rHuEPO on the fatty acid
      composition of platelet phospholipids in patients with ESRF treated with repeated
      haemodialysis. The study material included 25 patients divided into two groups:
      group I--14 patients treated with repeated haemodialysis, group II--11 patients
      also treated with haemodialysis in whom rHuEPO was administered subcutaneously in
      doses 2000 U twice weekly. In group I great differences in fatty acid composition
      were noted in comparison to the control group. In general, decreased content of
      unsaturated fatty acids was found in all phospholipid classes, except for
      phosphatidylcholine. In group II the changes in fatty acid composition were
      considerably less pronounced than in group I, in the case of many acids reaching
      the values observed in the control group. The obtained results suggest that
      rHuEPO improves changed platelet lipid metabolism in patients with ESRF treated
      with repeated haemodialysis.

PMID- 9273230
TI  - [The value of symptomatic yellowing of cytoplasm in leukocytes obtained from
      stomach contents in diagnosis of biliary gastritis].
AB  - Leucocyte cytoplasm is changed during long-term influence of bile in inflammation
      of gastric mucose. The symptom of gastric neutrophil yellow-cytoplasm has been
      analysed in 30-patient group after operation because of gastric peptic ulcer. The
      clinical usefulness is suggested in differential diagnosis of gastritis.

PMID- 9273231
TI  - [Circadian rhythm of cortisol in patients after reconstruction surgery of the
      esophagus using various intestinal segments for transplantation].
AB  - The authors determined the circadian rhythm of cortisol expressed as blood 11
      hydroxycorticosteroid level (11 OHCS) in group of healthy subjects and in 3
      groups of patients after the formation of an artificial oesophagus from the
      jejunum, large intestine and ileum and caecum. In all examined patients the
      normal circadian rhythm of 11 OHCS was maintained. In patients with oesophagus
      made up of jejunum and large intestine mean level 11 OHCS in blood was
      insignificantly higher in comparison with a group healthy subjects. In group
      patients with the oesophagus made up of ileum and caecum the 11 OHCS level in
      blood was significantly lower in comparison to the group of healthy subjects and
      to patients with oesophagus made up of jejunum and large intestine.

PMID- 9273232
TI  - [The value of radiologic examination of bones as part of hospital admissions
      procedures].
AB  - Based on radiological examinations of bone system done for 1518 emergent, post
      traumatic cases registered in an admission room, the authors have tried to
      perform a reliable analysis of the usefulness of the examinations. First of all,
      they have indicated that there were big differences between the requested x-ray
      examinations and their results. It has been noticed that the particular
      overstatement was employed during skull examinations especially for children, for
      which the detectability of changes in relation to the number of patients was
      equal to 7%. The more careful analysis of symptoms based on the more exact and
      precise physical examination could eliminate about 50% of x-ray examinations
      without any harm to patients and with an advantage to the hospital budget. It
      also seems that only a proper stimulus of such activity among clinicians and
      radiologists could give useful results.

PMID- 9273233
TI  - [Echocardiography examinations in children suffering from cutaneous forms of
      scleroderma].
AB  - In 34 children suffering from so called cutaneous forms of scleroderma and in 30
      healthy subjects echocardiographic cardiac assessment as well as doppler analysis
      of mitral valve function was performed. It was found that sclerodermic children
      suffered more frequently from cardiac valves regurgitation (especially
      insufficiency of mitral valve). However, these insufficiencies were usually
      negligible or corresponding to Io. Other changes detected in these children were
      as follows: significantly higher values of left ventricle shortening fraction,
      increased left ventricle mass index, and changes of mitral flow which may reflect
      impaired diasystolic function of left ventricle and, perhaps, impaired left
      atrium contraction. It is suggested that such changes could be corresponding to
      the beginning of cardiomyopathy.

PMID- 9273235
TI  - [Acute renal failure in the course of rhabdomyolysis after status epilepticus].
AB  - A 24 years old woman with sclerosis multiplex was admitted to our hospital after
      generalized seizures. In the first days of observation occurred symptoms of acute
      renal failure and liver damage with hemolysis. The differential diagnosis allowed
      us to recognize acute renal failure in the course of rhabdomyolysis. After a few
      hemodialysis normal renal function was achieved.

PMID- 9273234
TI  - [Soluble class HLA antigens in serum of patients with brain tumors].
AB  - The levels of soluble class I HLA antigens (s-HLA-I) in blood sera of patients
      with brain gliomas were studied before and after operation. It was found that
      sHLA material in sera was markedly decreased. The authors suggest the use of
      these examinations as one of the parameters of immune state of the oncologic
      patients before operation and in postoperative period.

PMID- 9273237
TI  - [A case of encephalitis of mixed Coxsackievirus B4 and rubella viral etiology in
      a 9-year old boy].
AB  - A nine-old boy was presented with encephalitis of mixed viral etiology Coxsackie
      B4 and rubella virus. The beginning of disease was enough sudden with convulsion
      and lost of consciousness. Further development of disease mild-the patients was
      discharged home in good general condition but with nervous super-excitability
      symptoms. It was the first case of children's mixed viral encephalitis recognized
      and treated in our Clinic.

PMID- 9273236
TI  - [Idiopathic Fanconi syndrome in an adult].
AB  - Fanconi syndrome is a complex destruction of proximal renal tubuli which leads to
      glycosuria, aminoaciduria, phosphaturia and uraemia. These disturbances are
      accompanied with hypophosphatemia, osteomalacia and frequently hypokalemia. A 32
      yrs. old woman diagnosed as suffering for 10 yrs. with Fanconi syndrome was
      admitted to the clinic with pain and numbness of the right leg which made walking
      difficult this resulted from progressive bone destruction. Biochemical
      disturbances and osteomalacia which are typical for Fanconi syndrome was
      confirmed in 1984. The reason for 3 hospitalizations in 1990-1992 were similar-
      especially leg pain and symptoms of uraemia. Recent X-rays showed osteomalacia
      with osteoporosis and progressive bone destruction. After she was put on a uremic
      diet, given vitamin D, calcium, phosphorus and sodium bicarbonate, there was a
      significant decrease in leg pain and relatively normal biochemical parameters.

PMID- 9273238
TI  - [A case of multiple intracranial meningiomas].
AB  - A case of a 91-years old woman is presented. She had multiple intracranial
      meningiomas, and the only symptom was the chronic headache. The diagnosis was
      made on the base of CT scan. The patient finally died. Postmortem examination
      confirmed the diagnosis.

PMID- 9273240
TI  - [Classification of non-granulomatous lymphomas].
AB  - Non-granuloma lymphomas (non-Hodgkin lymphoma) are neoplasms from lymphoid cell
      line. In this article the classification of non-granuloma lymphomas is presented
      according to actual knowledge.

PMID- 9273239
TI  - [Potential role of the endothelium in pathogenesis of atherosclerosis].
AB  - The endothelium has an unique role at the interface of the blood and the tissues.
      It is involved in numerous homeostatic function, metabolism of lipoproteins,
      regulation of vascular tone and plays a role in the immune response. Due to its
      anatomic position, the endothelium is a primary target for injuries and
      atheromatosis risk factors. Hypertension, diabetes mellitus, hypercholesterolemia
      and smoking can alter endothelial function. A reduced release of endothelium
      derived relaxing factors such as nitric oxide and an enhanced liberation of
      endothelium-derived contracting factors such as endothelin are common findings in
      the presence of atherosclerosis risk factors. These alterations of endothelial
      function are likely to contribute to the pathogenesis as well as progression and
      complications of atherosclerosis.

PMID- 9273241
TI  - [Atenolol in treatment of patients with airway obstruction].
AB  - It is well known that beta-2-blockers are contraindicated for patients with
      bronchial hyperactivity. Author discusses the clinical observations in relation
      to treatment with atenolol in circulatory system pathology.

PMID- 9273242
TI  - [Educational program for education of family physicians in clinical psychology
      and psychotherapy].

PMID- 9273243
TI  - [Edward Jenner (1749-1823)--benefactor to mankind (100th anniversary of the first
      vaccination against smallpox)].

PMID- 9273244
TI  - Flirting with disaster.
AB  - Labor pain management has changed dramatically during the last 20 years, and
      recently the nurse's role with epidural analgesia and anesthesia has been called
      into question. Cost-cutting measures in hospitals and clinics have forced some
      RNs into roles typically, and advisedly, reserved for a certified anesthesia
      provider--sometimes to the mother and baby's peril.

PMID- 9273245
TI  - Recent literature on cell stress & chaperones.

PMID- 9273246
TI  - Notes on the 40th conference of the American Biophysical Society.

PMID- 9273247
TI  - [A case of posterior dislocation of the shoulder with fracture of the humeral
      neck].
AB  - A case of posterior dislocation of the shoulder with concomitant fracture of the
      humeral neck and diagnostic difficulties are discussed. An axial radiograph of
      the shoulder was omitted at the first examination and posterior dislocation was
      unrecognized. It was diagnosed only after one month. Surgical reduction with
      Steinman pin and Kirschner wires fixation rendered good final outcome.

PMID- 9273248
TI  - [Treatment of intraarticular finger fractures with the help of the traction
      system of "pins and rubbers" according to Y. Suzuki].
AB  - The results of treatment of intraarticular finger fractures by means of Y.
      Suzuki's pins and rubbers traction system are presented. The system consists of 2
      3 thin K-wires and 2 rubber bands, is easy to assemble, effective, and less
      clumsy then the ones applied previously. It also allows for the reduction of
      palmar displacement of bony fragments. Sixteen intraarticular fractures have been
      treated. The average total range of motion of the injured PIP joint was 82
      degrees at the average follow-up of 8.5 months.

PMID- 9273250
TI  - [Use of bone grafts in acetabular wall deficit reconstruction during total hip
      replacement].
AB  - Results of cemented and noncemented total hip replacement with the use of bone
      grafts are presented. Forty-nine hips in 43 patients were operated. Mean age of
      the patient at the operation was 53 years (range 38-64). The follow-up ranged
      from 2 to 4 years. It has been concluded, that acetabular bottom and wall
      deficits should be filled with bone grafts, preferably corticocancellous ones.

PMID- 9273249
TI  - [Remarks on classification of Perthes disease].
AB  - The most commonly used classifications of Perthes disease are presented., their
      pros and cons discussed. The newest classification of Perthes disease proposed by
      Herring et al in 1992 is included. The ease of interpretation of the a-p hip
      radiographs, high reproducibility of the method and strict correlation between
      lateral pillar height and the final result of treatment make Herring's
      classification very useful. Its wide utilization may allow for uniform treatment
      of Perthes disease.

PMID- 9273251
TI  - [Modified Van Nes operation for treatment of congenital proximal femoral focal
      deficiency].
AB  - Van Nes rotation plasty was done in 5 children with congenital proximal femoral
      focal deficiency. Mean age at the operation was 8.7 years (range 38 months-16
      years), mean follow-up was 16 months (6-30 months). In 3 children full rotation
      at the level of knee joint was done; in 2 cases additional rotation at the level
      of tibial shaft was necessary. No neural and vascular complications were
      observed. In all children the ankle is at the level of the knee of normal
      extremity. The range of flexion of the prostetic knee is between 70 degrees and
      90 degrees. The review of the literature concerning the treatment of the most
      severe cogenital proximal femoral deficiencies is presented.

PMID- 9273252
TI  - [Free vascularized double barrel fibular graft for reconstruction of femoral
      deficit--case report and surgical techniques].
AB  - A case of 18 years old female treated for 11 cm femoral deficit due to comminuted
      fracture and secondary osteomyelitis is described. Free vascularized double
      barrel fibular graft has been used. The detailed delineation of surgical
      technique is given. Ten months after surgery complete healing and incorporation
      of the graft was found; the external fixation was removed. Excellent functional
      result has been achieved.

PMID- 9273253
TI  - [New electromyographic test for orthopedic diagnosis. Part II].
AB  - This study deals with mathematical assessment of physiologic and pathologic EMG
      frequency distribution by means of ranging. Material consisted of 161 pathologic
      EMG (63 myogenic cases, 98 neurogenic cases). In physiologic EMG power density
      distribution shows the highest values between 50 and 100 Hz, the lowest between
      200 and 250 Hz. From 0 to 50 Hz power density increases, from 100 to 250 Hz
      decreases. In patients with muscular diseases of different etiology the EMG power
      density spectrum is markedly different. The highest values appear more frequently
      between 0 and 50 Hz, sometimes also between 100 and 150 Hz. The frequency
      distribution allows mainly for assessing intensity of EMG pathology; is less
      useful for determination of its type.

PMID- 9273254
TI  - [Relationship between osteocalcin serum level and radiologic changes in long bone
      fracture healing--preliminary conclusions].
AB  - The osteocalcin serum level was monitored in 6 patients with long bone fracture.
      Immunohistochemical method was used at the day of fracture and also 7, 10, 14,
      21, and 28 days after. In 3 cases an autogenic bone marrow grafting was done and
      osteocalcin level was monitored. The progressive increase was observed in the 4th
      week after fracture.

PMID- 9273255
TI  - [The author's own method of local anesthesia for skin incision around implants
      during limb lengthening].
AB  - Infection around implants is the most frequently described problem during limb
      lengthening. Fast elimination of the inflammatory response is crucial for
      intensive mobilization and weight bearing of the extremity being elongated. Prior
      to the unloading incision of the skin stretched around the implant EMLA ointment
      was used repeatedly in 12 children. EMLA was applied 1-2 hours prior to the
      procedure and covered with an occlusive dressing. All skin incisions, also within
      inflamed areas were painless. The management described eliminates the need for
      general anesthesia and thus for hospitalization, lowers treatment costs and
      limits child's anxiety.

PMID- 9273256
TI  - [Treatment of bacterial osteomyelitis using ultrasonic energy waves].
AB  - The method and results of uncommon ultrasound treatment in 82 cases of
      osteomyelitis are presented. The method was supplemented with intraoperative Th
      99m isotope diagnostics as well as fluorescence based diagnosis to identify
      necrotic bone fragments. Ultrasound energy had advantageous effect on soft tissue
      healing and osteogenesis.

PMID- 9273258
TI  - [Methods for evaluating surgical treatment results of complete acromioclavicular
      dislocation].
AB  - Results of operative treatment for complete dislocation of acromioclavicular
      joint in 15 patients are presented. Joint reconstruction was performed according
      to Henry's modified method supplemented with supraclavicular deltoid and
      trapezius muscles suture. Three different scales were used for functional
      assessment of the shoulder girdle at the follow-up. Depending on evaluation
      method used, different results of treatment were achieved. The evaluation scale
      proposed by Taft et al is, in our opinion, the most useful one in clinical
      practice.

PMID- 9273257
TI  - [Evaluation of bone density in rats after hydrocortisone and microwave
      radiation].
AB  - The influence of hydrocortisone and microwave radiation on bone in rats have been
      investigated. Hydrocortisone hemisuccinate has been administered
      intraperitoneally for 12 weeks with concomitant microwave irradiation of two
      power densities. The results achieved indicate protective effect of
      electromagnetic microwave radiation on bone tissue exposed to corticotherapy.

PMID- 9273259
TI  - [Plaque radiotherapy of uveal malignant melanoma has redeemed its promise].

PMID- 9273260
TI  - [Inflammatory intestinal diseases--a heterogenic group of diseases].

PMID- 9273261
TI  - [The family of lipoprotein receptors is growing].

PMID- 9273262
TI  - [Intracytoplasmic sperm injection].

PMID- 9273263
TI  - [Treatment of spasmodic dysphonia with botulinum toxin].

PMID- 9273264
TI  - [MRI of the joints].

PMID- 9273266
TI  - [Why does recession decrease the incidence of mental disorders?].

PMID- 9273265
TI  - [Fever, progressive tetraparesis and respiratory paralysis in a patient with
      immune deficiency].

PMID- 9273268
TI  - [Life is teaching, but do we learn?].

PMID- 9273267
TI  - [To want and to say that one wants].

PMID- 9273269
TI  - [The Finnish term for pro-drug].

PMID- 9273270
TI  - [Post-traumatic stress disorder or maladjustment to stress?].

PMID- 9273271
TI  - [Revolution in asthma related hospital treatment].

PMID- 9273272
TI  - [Yeast allergy--does it exist?].

PMID- 9273273
TI  - [Atopic eczema: is the treatment practice based on research results?].

PMID- 9273274
TI  - [Identify the allergic rhinitis in your patient].

PMID- 9273275
TI  - [Use of inflammatory protein in asthma diagnosis].

PMID- 9273276
TI  - [How to get evidence of the bronchial obstruction in a child?].

PMID- 9273277
TI  - [Asthmatic children are inhaling steroids--should we be afraid of side-effects?].

PMID- 9273278
TI  - [Insurance medicine as a specialty].

PMID- 9273279
TI  - [Social insurance and health care].

PMID- 9273280
TI  - [The changing role of private personal insurance].

PMID- 9273281
TI  - [The doctor as an advocate for the patient in the insurance system].

PMID- 9273282
TI  - [Social security in Finland].

PMID- 9273283
TI  - [Work disability in social insurance].

PMID- 9273284
TI  - [Work capacity of coronary disease patients after coronary balloon dilatation and
      coronary artery bypass].

PMID- 9273285
TI  - [Musculoskeletal pain disorders].

PMID- 9273286
TI  - [Depressive disorders].

PMID- 9273287
TI  - [Personality and adjustment disorders].

PMID- 9273288
TI  - [Work disability and alcohol problems].

PMID- 9273289
TI  - [Causality in insurance medicine].

PMID- 9273290
TI  - [Degenerative diseases and trauma].

PMID- 9273291
TI  - [Post-traumatic stress disorders].

PMID- 9273292
TI  - [Whiplash injuries].

PMID- 9273293
TI  - [Epicondylitis and tenosynovitis or peritendinitis as an occupational disease].

PMID- 9273294
TI  - [Travel insurance].

PMID- 9273295
TI  - [Risk assessment and responsibility selection].

PMID- 9273297
TI  - [The concept of handicap].

PMID- 9273296
TI  - [Private sickness insurance].

PMID- 9273298
TI  - [Benefits paid for by the Social Insurance Institution and the assessment of
      handicap].

PMID- 9273299
TI  - [Compensation of handicap in statutory accident insurance and traffic insurance].

PMID- 9273300
TI  - [Dopamine D2 and serotonin 5HT2 receptors: functions, interactions and clinical
      consequences in schizophrenia].
AB  - This didactic paper reviews the different receptors families, the principal
      characteristics of the dopaminergic and serotoninergic receptors and their role
      in the aetiology and pathophysiology of schizophrenia. The current knowledge on
      interactions between serotoninergic and dopaminergic systems is also summarized.
      The theoretical and potential interests of these interactions in alleviating
      neuroleptic-induced extrapyramidal symptoms and improving negative signs in
      schizophrenia are also examined.

PMID- 9273301
TI  - [Schizophrenia: receptors and clinical aspects].
AB  - Growing knowledge in receptors and clinical aspects of schizophrenia has led to
      new models of understanding. These models emphasize the role of anxious and
      depressive dimensions in the constitution of clinical symptomatology. A more
      precise evaluation of these dimensions seems necessary to try to discover more
      specific drugs.

PMID- 9273302
TI  - [New chemotherapy approaches to psychoses].
AB  - Particular features are involved in the atypical antipsychotic concept:
      efficacity on refractory patients and negative symptoms, less or no
      extrapyramidal side effects, less tardive dyskinesia and less increase in
      prolactinemia. The imprecision of the atypical neuroleptic class must be
      underlined. In fact, the pharmacological agents who are included in this class
      potentially induce few neurological side effects. These effects appearing in
      doses very much higher than in the therapeutical range. In this case, atypical
      should refer to a particularity in the links between doses, efficacy and side
      effects more than to a definition in a specific category. Dopaminergic hypothesis
      is explained more and more by a dopaminergic system dysregulation than by a
      simple dopaminergic hyperactivity. This dysregulation might be autonomous or
      linked to other monoaminergic systems. These new antipsychotics show affinity for
      different monoaminergic receptors. After clozapine, several agents are now
      available (risperidone) or just about to be (olanzapine, seroquel, sertindole,
      ziprasidone, zotepine). Therapeutical effects are probably linked with a dual
      antagonist effects on 5HT2 and D2 receptors. The atypical antipsychotic efficacy
      on negative symptoms remains controversial. While very few patients are found to
      be "purely" negative, most of the schizophrenic patients will show sooner or
      later some negative symptoms mixed with positive ones. The obvious difficulties
      in methodological and clinical evaluation of negative symptoms are at least dual:
      depressive symptoms; extrapyramidal side effects. Secondary negative symptoms
      usually don't last, while primary negative symptoms are more permanent. Kraepelin
      describes them as the avolutionnal syndrome of dementia praecox. Usually negative
      symptoms improve during therapeutic trials, including those using classical
      neuroleptics. This should not lead us to the conclusion that we have today at our
      disposal pharmacological agents effective on avolutionnal syndrome or primary
      negative symptoms. More studies are still necessary. Similarities and differences
      between the new antipsychotic are not yet evaluated, except partly for clozapine
      and risperidone. Some new neuroleptics might simplify greatly the therapeutic
      range. Studies concerning risperidone clearly prove its efficacity on a daily
      dose of 6 +/- 2 mg. A daily dose of 10 mg doesn't bring any additional
      improvement. This aspect must be underlined while the efficacy-dose ratio of the
      classical neuroleptics are still questioned. Consequently too many patients might
      be given insufficient doses and others excessive doses resulting in side effects
      and no additional benefits. These new antipsychotics must add a positive
      modification in schizophrenic care. They might lead to a limited use of
      additional therapeutics and a better observance thus allowing less relapses and
      less rehospitalisations.

PMID- 9273303
TI  - [Syndromic and diagnostic heterogeneity of schizophrenia].
AB  - Heterogeneity in schizophrenia is an old concept, already evoked by Kraepelin and
      Bleuler. During the XXth century, this conception has led to a multiplication of
      diagnostic systems, which allow to define similar groups of patients from a
      country to another. However, these systems cannot select homogeneous groups of
      patients, since they include "polythetic" diagnostic criteria. Moreover,
      comparison of groups selected by different diagnostic systems shows that they are
      very heterogeneous too. It is why a polydiagnostic approach could be a relevant
      strategy: this consists of using many diagnostic systems at the same time in
      order not to select an arbitrary subgroup of schizophrenic patients over another.
      Therefore, several ways are possible to isolate the most homogeneous groups of
      patients from the heterogeneous population obtained with the polydiagnostic
      approach, depending on the aim of the research. A first possibility is a
      dimensional approach, in individualizing syndromic dimensions from
      psychopathological scales using principal component analyses. This approach might
      be useful to test the efficiency of an antipsychotic on a syndromic dimension. A
      second possibility is to identify groups of patients characterized by the largest
      homogeneity inside each group and the largest differences between groups. One way
      to perform it is the cluster analysis. Authors present a study using such a
      method: 5 different subgroups are identified in 138 schizophrenic patients. This
      approach is useful to study a subgroup of patients in comparison with a control
      group. A third possibility is represented by Carpenter et al. approach (7) with
      the definition of the deficit syndrome; a very homogeneous group of patients
      defined by standardized criteria can be individualized and characterized by
      physiopathologic anomalies.

PMID- 9273304
TI  - [A new study of secondary effects in prescribing practices of neuroleptics].
AB  - Within the context of our knowledge of the neuroleptics, side-effects have not
      only been considered for a number of years as an unavoidable element of these
      agents; they in fact practically constitute a defining feature of such drugs.
      Advances in knowledge and the availability to prescribing practitioners of so
      called "atypical" neuroleptics allow some redefinition of the above problem. A
      multidimensional approach which goes beyond more nosographic considerations, and
      the addition of a temporal dimension to a question for too long reduced to its
      spatial aspect are new elements which help put the issue of side-effects in
      perspective. However, any examination of this subject must also take into account
      the quality of life and the subjective experience of patients undergoing
      treatment with neuroleptics, since these considerations represent important
      pathways for the future. Such analysis must also take into account the current
      situation, in which excessive prescription of corrective agents, the prevalence
      of co-prescription of psychotropic agents and wide variations in prescribing of
      neuroleptics (for too long overlooked, in terms of both analysis and education)
      have given rise to coercive control strategies. The system of Opposable Medical
      References (OMR) forms part of a panoply of measures aimed at control rather than
      education. However, education constitutes a key element in this field if the goal
      of re-appropriation is to be achieved.

PMID- 9273305
TI  - [The PANSS (Positive And Negative Symptom) Scale].
AB  - The PANSS scale, first proposed by Kay et al. (1987) and translated into French
      is an evaluation scale of 30 disparate items scored from 1 to 7 for
      psychopathological symptoms observed in patients presenting psychotic syndromes,
      especially schizophrenic states. A semi-structured interview (translated into
      French by J.P. Lindenmayer) and precise definition of the different degrees of
      symptomatic, severity make it possible to obtain satisfactory between-assessor
      and test-retest fidelity. Three scores obtained with this evaluation tool are
      generally calculated for evaluating three dimensions of the syndrome: positive,
      negative and general psychopathology, as part of a categorial or dimensional
      perspective. The main studies validating the PANSS scale have involved several
      factorial analyses and comparison with data obtained using other schizophrenia
      scales such as Nancy Andreasen's SANS and SAPS scales. The three main factors
      isolated correspond to the clinical dimensions: positive, negative and
      "disorganization". Currently, the PANSS scale is being used increasingly more
      often. It allows study of the symptomatic profile in a wide population of
      psychotic patients and evaluation of the prognostic influence of positive and
      negative dimensions. It does however appear to be susceptible to change. Recent
      research projects are attempting to confirm initial findings and to analyse the
      general relevance of the reference conceptual model used by the authors.

PMID- 9273306
TI  - [Schizophrenia, from classification to dimensions: value of longitudinal
      studies].
AB  - There is no clinical sign, cognitive impairment or physiological abnormality
      pathognomic for schizophrenia. Aetiological factors and neurophysiological
      abnormalities appear to be heterogeneous. On the other hand, among the three
      symptomatic dimensions (negative, positive and disorganized), specific negative
      symptoms may present as early signs in childhood, may exist as essential signs
      marking disease onset, may be stable during disease progression, may predict an
      unfavourable long-term outcome, may have a significant genetic component in
      affected families, and may, be linked to neurological abnormalities when present.
      Of these symptoms, anhedonia and motivational disorders are the most stable and
      have the greatest predictive value. They may reflect a vulnerability common to
      the schizophrenic spectrum and account for the subsequent development of other
      symptomatic dimensions; this may be observed even when multiple aetiological
      factors are involved. In relation to their mechanism of action, the therapeutic
      effects of neuroleptics are consistent with this hypothesis.

PMID- 9273307
TI  - 1st Meeting of EURO DURG, the European Drug Utilization Research Group. Hungary,
      27-30 June 1996. Abstracts.

PMID- 9273308
TI  - [Prosthetic indications of single-phase implants].

PMID- 9273309
TI  - [Dental implants. Innovations--quality assurance--acquisition].
AB  - In connection with implants the characteristics and possibilities of innovation
      are studied taking into consideration the measures prescribed by the public
      acquisition law. The author stresses that the Association for Facial-Mandibular
      and Oral Surgery has to take an initiative role in the innovation of implants.

PMID- 9273310
TI  - [Stomatologic implications of Turner syndrome. I. Dental caries and periodontal
      status].
AB  - Turner's syndrome is a chromosomal abnormality with additional deficiency in
      gonadal and adrenocorticotropic secretions. The most frequent oral findings are:
      high palatal vault and hypoplastic mandible. The aim of the present study was to
      investigate the caries prevalence and periodontal condition of patients with
      Turner's syndrome. The study population consisted of 24 patients with Turner's
      syndrome and 24 healthy control girls. Mean age were 24.5 years in both groups.
      Significantly lower DMF-T mean values were found in patients with Turner's
      syndrome compared with the healthy controls. From among the investigated
      periodontal parameters probing depth showed no difference between the two groups,
      but gingival index and plaque index were significantly higher in patients with
      Turner's syndrome.

PMID- 9273311
TI  - Degradation of polycyclic aromatic hydrocarbons by manganese peroxidase of
      Nematoloma frowardii.
AB  - The degradation of polycyclic aromatic hydrocarbons by a manganese peroxidase
      crude preparation of Nematoloma forwardii was demonstrated for a mixture of eight
      different polycyclic aromatic hydrocarbons, and the five individual polycyclic
      aromatic hydrocarbons phenanthrene, anthracene, pyrene, fluoranthene, and
      benzo[alpha]pyrene. Oxidation of polycyclic aromatic hydrocarbons was enhanced by
      the addition of glutathione, a mediator substance, able to form reactive thiyl
      radicals. Glutathione-mediated manganese peroxidase (1.96 U ml(-1)) was capable
      of mineralizing [14C]pyrene (7.3%),[14C]anthracene (4.7%),
      [14C]benzo[alpha]pyrene (4.0%), [14C]benz(alpha)anthracene 2.9%), and
      [14C]phenanthrene (2.5%) in a period of 168 h. This is the first description of
      direct enzymatic mineralization of polycyclic aromatic hydrocarbons by manganese
      peroxidase, and indicates their important role in the oxidation of polycyclic
      aromatic hydrocarbons by wood-decaying fungi.

PMID- 9273312
TI  - Determination of bacterial cell surface hydrophobicity of single cells in
      cultures and in wastewater in situ.
AB  - Bacterial cell surface hydrophobicity is one of the most important factors that
      influence bacterial adhesion. A new method microsphere adhesion to cells, for
      measuring bacterial cell surface hydrophobicity was developed. Microsphere
      adhesion to cells is based on microscopic enumeration of hydrophobic, fluorescent
      microspheres attaching to the bacterial surface. Cell surface hydrophobicity
      estimated by microsphere adhesion to cells correlates well with adhesion of
      bacteria to hydrocarbons or hydrophobic interaction chromatography for a set of
      hydrophilic and hydrophobic bacteria (linear correlation coefficients, R2, were
      0.845 and 0.981 respectively). We also used microsphere adhesion to cells to
      investigate the in situ properties of individual free-living bacteria directly in
      activated sludge. Results showed that the majority of the bacteria were
      hydrophilic, indicating the importance of cell surface hydrophobicity for
      bacterial adhesion in sludge, and for the overall success of the wastewater
      treatment process.

PMID- 9273313
TI  - Polycaprolactone depolymerase produced by the bacterium Alcaligenes faecalis.
AB  - Several microorganisms were isolated as bacteria degrading polycaprolactone
      (PCL), and one of them, a strain B273 identified as Alcaligenes faecalis, was
      selected. Because this strain produced only slight PCL depolymerase activity, the
      hyperproducing mutant, TS22, was isolated after UV irradiation. Synthesis of PCL
      depolymerase was derepressed, probably based on the altered regulation of
      metabolic pathways in strain TS22. The partially purified enzyme hydrolyzed p
      nitrophenyl fatty acids and triglycerides other than PCL, but not poly(3
      hydroxybutyrate), indicating that PCL depolymerase may be a kind of lipase.

PMID- 9273314
TI  - [Molecular analysis of certain derivatives of mutants with the unstable white
      starka allele].
AB  - Molecular analysis of several mutations of the white locus was performed. The
      mutations were obtained as a result of mutagenesis in the unstable white-starka
      locus described previously. A large insert (approximately 15 kb in length)
      downstream of the first exon of the white gene was shown to be partly excised.
      Simultaneous excisions of various regions from the natural regulatory region of
      the white locus were also observed. Restriction enzyme analysis showed that the
      observed mutations and reversions resulted from large deletions from the
      regulatory gene region. Southern and Northern blot hybridization showed the
      presence of unknown regulatory regions within and outside the insert.

PMID- 9273315
TI  - [Genetic control of metabolism of a mutagenic analog of 6-N-hydroxylaminopurine
      bases in Saccharomyces cerevisiae yeasts].
AB  - Yeasts were shown to utilize 6-substituted adenine analogues as a purine source
      via the reutilization pathway leading to the formation of inosine monophosphate
      (IMP). This occurs because the ade12 strains with blocked conversion of IMP into
      adenosine monophosphate (AMP) cannot grow on media containing the above analogues
      as a sole purine source. Haploid strains with the double mutation ham1 ade2 or
      ham1 ade5 were also incapable of growing on a medium with 6-N-hydroxylaminopurine
      (HAP) as a sole purine source. However, in this case, this inability was caused
      by the occurrence of recessive lethal mutations rather than by a defect in purine
      reutilization. Yeast adenine aminohydrolase (AAH) can deaminate HAP to
      hypoxanthine. Adenine aminohydrolase (AAH) was uniformly active both in strains
      with a mutation in the HAMI gene and in strains wild-type with respect to this
      trait.

PMID- 9273316
TI  - [Phenotypic expression of a 100-pair nucleotide deletion in the regulatory region
      of the Bacillus subtilis riboflavin operon].
AB  - Assessment of specific activity of riboflavin synthase and the level of
      riboflavin accumulation in strains with a 110-nucleotide deletion in the
      regulatory region of the riboflavin operon showed that this deletion specified
      semi-constitutive expression of the operon. This was assumed to be connected with
      the elimination of three nucleotides from a potential transcription
      antiterminator.

PMID- 9273317
TI  - [Fusion of glutathione S-transferase with the N-terminus of yeast Sup35p protein
      inhibits its prion-like properties].
AB  - The yeast Saccharomyces cerevisiae SUP35 gene that encodes the Sup35p protein
      homologous to the translation termination eRF3 factor of higher eukaryotes is
      essential to replication of the nonchromosomally inherited [psi+] determinant.
      The nonsense suppressor phenotype of this determinant was assumed to be dependent
      on a specific conformational state of the Sup35p protein; the transition to this
      state leads to partial inactivation of this protein. In terms of this hypothesis,
      the Sup35p protein can, like mammalian prions, induce its own specific
      conformation via protein-protein interactions in the newly synthesized Sup35p
      molecules; in this way, inheritance of the [psi+] phenotype is ensured in a
      series of cell generations. In recent years, this hypothesis has been
      experimentally verified. Allele substitution of the wild-type SUP35 gene by its
      chimeric GST-SUP35 version, which encodes the glutathione S-transferase sequence
      fused with the N end of Sup35p, was shown to cause elimination of the [psi+]
      determinant. The ability to eliminate [psi+] is a recessive trait, because
      fusions heterozygous for the GST-SUP35 allele did not lose this trait.
      Elimination of [psi+] seems to be caused by inability of the chimeric protein to
      bring about oligomerization. The obtained data indicate that the chimeric protein
      manifests attenuated terminating activity but can interact with the eRF1
      translation termination factor encoded by the SUP45 gene.

PMID- 9273318
TI  - [Evaluation of the heritability of basic parameters of aging in Drosophila
      melanogaster].
AB  - Based on 28 annuity curves of Drosophila melanogaster, the heritability of
      Gompertz mortality parameters was estimated; its value was 0.7-0.8. Mortality
      parameter R0 was shown to be inversely proportional to the square of alpha. Some
      data indicate the monogenic control of interlinear differences in these
      parameters. A hypothesis on the localization of these genes on chromosome 2 is
      discussed.

PMID- 9273319
TI  - [Presymptomatic DNA diagnosis of spinocerebellar ataxia type 1].
AB  - Hereditary autosomal dominant ataxias is a clinically and genetically
      heterogeneous group of diseases characterized by a progressive ataxia combined
      with the signs of multisystem involvement of the brain and spinal cord. The
      modern classification of these disorders of the central nervous system is based
      on recent advances in molecular genetics. In a form of dominant ataxia,
      spinocerebellar ataxia type 1 (SCA1), the mutation consists of an increased
      number of copies (expansion) of trinucleotide repeats within the causative gene.
      This mutational mechanism is characteristic of a group of hereditary
      neurodegenerative diseases. Revealing this phenomenon provided a tool for direct
      DNA diagnosis of SCA1 at any stage of the disease, including the preclinical one.
      This is the first reported case of a direct DNA diagnosis of SCA1 in Russia. The
      diagnosis was performed in five healthy persons from the risk group, i.e.,
      relatives of patients with a molecularly proven SCA1. Three persons were
      diagnosed to be presymptomatic carriers of the mutant SCA1 gene; in two persons,
      the mutation was not found. A complex of moral, ethical, medical, and social
      problems connected with the application of direct DNA testing of SCA1 in genetic
      counselling is discussed.

PMID- 9273320
TI  - [Cytogenetic disruption in adolescent children from the Kemerovskaya Region as an
      indicator of adverse ecological conditions of the region].
AB  - Results of a population and cytogenetic survey conducted on groups of adolescents
      from ecologically different parts of Kemerovskaya oblast, a large industrialized
      area in Western Siberia, are presented. Significant inter-group variations in the
      frequencies of spontaneous chromosomal aberrations were detected. In adolescents
      from the small miners' towns of Tashtagol and Myski, located in the southern part
      of the region, the highest frequencies of chromosome aberrations were revealed
      (5.87 +/- 0.62% and 6.72 +/- 0.54%, respectively). The peculiarities of the
      qualitative spectrum of cytogenetic defects observed suggested that the
      populations studied were exposed to radiation. The mean frequency of chromosome
      aberrations in groups of adolescents from Kemerovo, a large center of chemical
      industry, was equal to 3.49 +/- 0.44%, which is an additional evidence of
      mutagenic exposure. Chromosomal mutagenesis in this case is thought to be induced
      mainly by chemical genotoxic agents. However, the mutagenic effects of low doses
      of radiation cannot be excluded.

PMID- 9273321
TI  - [Structure-mutagenic activity relationships on the TA100 strain of Salmonella
      typhimurium exposed to a series of halogenated hydrocarbons and short-chain
      alcohols].

PMID- 9273322
TI  - [Mutagen-modifying effects of beta-carotene in vivo].
AB  - A chromosome aberration test on bone marrow cells of C57B1/6 mice showed that
      beta-carotene (BC) applied by oral administration as a E160a food dye (30% oil
      suspension) at doses of 0.5, 5, and 50 mg/kg simultaneously with cyclophosphamide
      (CPA) and dioxidine (DN) injected intraperitoneally for a period of 24 h did not
      modify their clastogenic effects. If the animals were pretreated with perorally
      administrated beta-carotene dye at doses of 5 and 50 mg/kg (corresponding to 1.5
      and 15 mg/kg of BC) for 5 consecutive days, a statistically significant reduction
      in the clastogenic effect of the DN injected for 24 h but not the CPA was
      observed. In another set of experiments, E160a and clastogens were administered
      simultaneously for 5 consecutive days, and the animals were killed 6 h after the
      last treatment. In this case, BC at the dose of 0.15-15 mg/kg statistically
      significantly reduced the clastogenicity of DN at all doses used, and of CPA at
      doses of 1.5 and 15 mg/kg.

PMID- 9273323
TI  - Geriatrics photo quiz. Pneumococcal pneumonia.

PMID- 9273324
TI  - [Pharmacokinetic variations in anticonvulsants in Mexican epileptic women during
      different stages of the postpartum period].
AB  - During pregnancy, there are several physiological changes that influence the
      kinetics of medication administrated during this time. These physiological
      changes are not reestablished immediately during delivery; so, its concentration
      in biologic fluids is different when is administered immediately after delivery,
      than several weeks after. The purpose in this work was to identify the changes of
      pharmacocinetics constants for fenitoin and carbamacepine, in epileptic patients.
      When the same dose is maintained, during different times of postpartum. In 20
      Mexican epileptic women, the plasma and milk concentrations of fenitoina during
      60 day postpartum and in 14 carbamacepine was determined. In all the patients
      pharmakocinetics of anticonvulsivant, in each study period (5, 15, 30, 45 y 60
      days postpartum). Excretion index of maternal milk was determined. Maximal
      plasmatic concentration of fentoine had no variation; however, carbamacepine was
      higher during the late period. There were no differences in the areas under curve
      and life all the middle of elimination and in excretion index.

PMID- 9273326
TI  - [Severe syndrome of ovarian hyperstimulation. Incidence, value of criteria of
      risk factors and preventive methods].
AB  - Statistical analysis; square Chi test, Pearson, were practiced, from 1994 to
      1996. There were 368 hyperstimulated cycles; three SHOS cases without risk
      factors and 28 cases with risk factors without SHOS. Risk factors presented were:
      average seric estradiol 6643.59 +/- 2320 pg/ ml; average follicles: 26.6 +/- 6.9;
      ovules recuperated by aspiration: 19.32 +/- 9.1. There were five groups according
      to preventive methods: albumin (13 patients, coasting (one patient); albumin
      coasting (11 pacientes); albumin-embryo freezing (3 patients); embryo freezing
      (one patient). None of the patients presented SHOS.

PMID- 9273325
TI  - [Endometrial ablation by liquid heat using the EnAbl system in patients after
      abdominal hysterectomy. Study of safety].
AB  - Security and efficacy of an EnABL, were evaluated; this system had been designed
      for endometrial ablation by liquid heat in uterine cavity. Eleven patients were
      included, from the Outpatient Department (INP), programmed for different causes
      that objectives of this study for abdominal hysterectomy due to abnormal uterine
      bleeding. The study was approved by Ethical and Scientific Committees. Each
      patient had preoperative studies, endometrial biopsy, PAP, and ultrasound, in
      series. The patients with uterus larger than 14 cm, possible cancer; younger than
      18 year, or with active bleeding at the time of hysterectomy, were excluded. Each
      patient received a schema of standard endometrial suppression. The system was
      applied previously to TAH; 2271 measurements of temperature at one minute
      intervals were done during liquid heat application. Surgical pieces were sent to
      histology to analyze the thermic damage through macroscopic aspect, HE tinction
      and an immunohistochemical cellular viability of NADH test. The thermal damage by
      macroscopic appearance was 4.33 +/- 1.03 mm, with HE of 4.15 +/- 0.75 mm and with
      the tinction of NADH of 4.25 mm +/- 0.79. The maximal damage by macroscopic
      appearance was 4.33 +/- 1.03 mm, with HE of 4.15 +/- 0.75 mm, and with NADH it
      was 4.25 mm +/- 0.79. The maximal damage was by macroscopic appearance was 6.0 mm
      and the minimal one was 2.0 mm. In evaluation by H/E, maximal was 5.1 mm and the
      minimal one was 2.3 mm. In NADH tinction maximal was 4.25 and minimal 2.4 mm.
      Horizontal analysis showed eight patients with major thermal damage at 4 mm; and
      two patients with lesser damage at 4 mm. Sub-serous temperatures measured with
      thermopairs, were done 1504 times, in total. Average was 36.28 degrees C, ranging
      35 to 37 degrees C. Maximal temperature was 45 degrees C, 1-2 mm, bellow from
      serous surface of uterus, and the last one was 28 degrees C. The serous
      temperatures measured by infrared radiation were done 767 times with an average
      temperature of 34.6 degrees C. Average was 34-35 C, with standard deviation of 1
      2 degrees C. Maximal temperature was 40 degrees C and minimal 29 degrees C. There
      were no adverse effects. This study shows that EnAbl system is an efficacious
      method.

PMID- 9273327
TI  - [Bacterial vaginosis. Relation between the vaginal flora and the vaginal
      epithelial cells under different treatments. Ultrastructural study].
AB  - At this study we analyzed morphologic relation with vaginal ephitelium, in women
      with bacterial vaginosis, in pre-treatment; first post-treatment and second post
      treatment using metronidazol (oral), and clindamycine (intra-vaginally). From 20
      patients with bacterial vaginosis, 10 received oral metronidazol, 500 mg/b.i.d.
      during seven days; the other patients received, clindamycine 2% intravaginal,
      once a day, during seven days. Couples received metronidazol. In pre-treatment,
      cellular prolongations produced greater adhesion of bacteria, and rests of
      cellular unions with adhered bacteria. There was penetration of some bacteria to
      epithelial cells, confirming this with serial cuts and discarding superposition
      in the cells. This penetration was found in five cases y persisted during the
      first and second post-treatment. In the first post-treatment, cellular groups
      without bacteria, were found. The presence of lactobacillus was low, increasing
      afterwards. The presence of yeasts was in the first post-treatment, and in some
      cases persisted. It is important to differentiate intracellular bacteria and to
      know the related characteristics with bacterial penetration, for an adequate
      prescription and a better use of medication, avoiding possible damage. The
      presence of bacteria may be one of the causes for bacterial vaginosis
      reincidence.

PMID- 9273328
TI  - [Identification of molecular nexus between infection and premature rupture of
      membranes].
AB  - The tumoral necrosis factor alfa (TNF-alpha) has been characterized as a signal
      contained in chorioamniotic membrane with premature rupture of membrane
      complicated with infection, inducing enzymes that degrade extracellular matrix
      components in fetal membranes. This cytocine is normally produced of immune
      system cells as a response to contact with infectious agents, and its
      identification is a direct molecular nexus between inflammatory response and
      development of premature rupture of membranes.

PMID- 9273329
TI  - [Ultrastructure of the tracheal epithelium in preterm neonates treated with
      mechanical ventilation].
AB  - Tracheal epithelial damage, was evaluated in prematures that where intubated and
      with mechanical ventilation; biopsies were taken in seven preterm neonates;
      weight was 1100 to 2350; five were by cesarean section, y one via vaginal.
      Bronchial culture was negative in five, in one Lysteria monocitogena, and in
      another one Pseudomonas spiralis; biopsy was taken at different times o
      intubation. Five died because of pneumonia associated to other diseases. In
      optical and ultrastructural study it was found that with one day of intubation
      there was cilia loss; with three days of ventilation there was ciliary cells
      loss, and not ciliary cellular death and there were no cellular unions. In one
      case with three days of ventilation and 17 days of post-extubation with infection
      by Pseudomonas, ulcerated zones and edema were found. At 14 days there necrosis
      zones, increase in collagene. At 17 days there were ulcerated zones to the
      muscular layer with fibrosis and cellular rests at tracheal path. So, mechanical
      ventilation and the presence of a catheter, damage bronchial epithelium since the
      first 24 hours.

PMID- 9273330
TI  - [Quantification of lamellar bodies in amniotic fluid: a method for the evaluation
      of fetal pulmonary maturity].
AB  - It was tried to know the counting up of lamellar bodies in amniotic fluid, as a
      test of fetal pulmonary maturity, comparing it with neonatal evolution. 31
      samples of amniotic fluid of different ages of gestation, were obtained, lamellar
      bodies were quantified with a standard equipment of hematic counting, and
      comparing with neonatal evolution, sensitivity, specificity, positive predictive
      value, and negative predictive value are established. The established
      concentration of 30,000/l by comparison with Lecitine/Esfingomieline and with
      Fosfatidilglycerol was used. From 29 patients with counts greater than 30,000,
      none presented Respiratory Difficulty syndrome (SDR); and from two patients with
      lower counts, one presented SDR and one had normal neonatal evolution.
      Sensitivity was 96%; specificity was 100%; predictive positive value, 50%; and
      negative predictive value was 100%. Because of this, the test is so useful in
      practice. Its statistical values, its minimal cost; easiness to do, and equipment
      availability, justify this test as a first election.

PMID- 9273331
TI  - [Cervical cytology].

PMID- 9273332
TI  - ["Initial results of the first ambulatory program for in vitro fertilization in
      Mexico"].
AB  - Infertile couples treated with in vitro fertilization and embryo transfer (IVF
      ET) seeking highest standards of case. The new programmes of IVF-ET are under
      pressure to generate as quickly as possible acceptable pregnancy rates. We report
      our experiences at a new IVF clinic, performing conventional IVF-ET and oocyte
      donation. Patients were treated in groups, their menstrual cycles were previously
      synchronized with luteal phase noretisterone. Both variants of IVF produced
      clinical pregnancies since the start of activity. In this paper the logistic and
      methodology are discussed. Today the aim of the programme is increasing the
      efficiency and efficacy of same.

PMID- 9273333
TI  - [Colposcopy and cervical biopsy in patients with routine Papanicolaou smear].
AB  - The objective of this report was to assess the sensitivity and specificity of Pap
      smear and to evaluate if routine colposcopy can improve cervical screening. One
      hundred and fifty patients undergoing routine cervical cytologic screening in our
      outpatient clinic were randomly selected. All patients were evaluated by
      colposcopy and cervical punch biopsy. Pap smears and biopsies specimens were
      interpreted independently. Colposcopy was performed and interpreted without
      knowledge of cytologic or histologic findings. The statistical analysis was
      carried out with a chi square (chi 2) test. A P value of less than 0.05 was
      considered significant. Twenty three patients (15.3%) who had biopsy proved to
      have cervical pathology. Pap smear identified only 4/23 (17%) of these patients.
      Colposcopy noted atypical transformation zones in 20/23 (97%), P < 0.001).
      Fifteen of 27 patients (55.5%) with negative Pap smears had colposcopic
      anormalities and histologically proved cervical intraepithelial neoplasia (CIN).
      We concluded that it is necessary to improve sensitivity and that colposcopy may
      enhance cervical screening particularly in women with otherwise negative
      Papapnicolaou smears.

PMID- 9273334
TI  - [En block hysterectomy. Institutional experience of 6 years].
AB  - On block hysterectomy is defined as the removal of the gravid uterus with its
      gestational content in situ. The described indications for the realization of
      this procedure are neoplastic process as the most frequent cause; septic process,
      persistent trophoblastic diseases, and hemorrhage due to anomalous placentation.
      This is a retrospective, descriptive study of twelve cases of on block
      hysterectomy collected from January 1989 to December 1994 at Instituto Nacional
      de Perinatologia. An average age of 33.4 years was found. The number of
      pregnancies for this patients in average was found to be 4.1. The gestational age
      was established between 9 to 29 weeks. Four patients with a 4 or more previous
      miscarriage background. There were two reported cases having a multiple
      gestation. Among the complications found, there were three cases of hipovolemic
      shock and one with abcess of vaginal cupula. The average days of hospitalization
      was 5.3 days. We found no mortality at all in this study, and the histopathologic
      correlation accorded in 100% of the cases. In this five year review, 12 cases of
      on block hysterectomy were found, being the most frequent reason for it's
      realization the persistent trophoblastic diseases; severe hemorrhage in second
      place, and serious infection process in third. The observed complications were
      derived from the hemodynamic compromise of each patient. Even though on block
      hysterectomy is one rarely seen procedure, it most be in mind as an alternative
      therapeutical instance it most be carried out in third level institutions, with
      technology and human resources capable of solving any complication derived from
      this kind of surgery.

PMID- 9273335
TI  - [Preoccupation women have and should have in watching their health].
AB  - The American College of Obstetricians and Gynecologists, since its beginning
      established three main objectives: 1. Education of physicians, 2. Education for
      patients, 3. To improve health care for women. The time has confirmed that
      through its programs the following has been reached: 1. Diminution in maternal
      mortality, 2. Diminution in newborn mortality, 3. Diminution in cervical cancer.
      The following is recommended: Exercise, adequate diet, evaluation tests, early
      diagnosis, hormonal therapy when recommended by the physician, for a prolonged,
      healthier, and more productive life.

PMID- 9273336
TI  - [Cesarean section: science or anxiety? Eleven years of institutional experience].
AB  - The increasing rise of cesarean section rate invites to analyze its indications.
      The present study was done from 1985 to 1995, which means 11 years of study with
      38,407 cases. Frequency and clinical indications were analyzed. As to births,
      frequency was 40.6%. Main causes were: Iterative section 38.2%; cephalopelvic
      disproportion 28.1%; pelvic presentation, 23.4%; hypertensive disease in
      pregnancy 16.3%; and acute fetal suffering, 10.9%. The careful observation of
      indications in every institution, may produce better reasons for reducing such
      high indexes.

PMID- 9273337
TI  - [Management of refractory autoimmune thrombocytopenic purpura during pregnancy,
      Review of the literature and report of three cases].
AB  - The immune thrombocytopenic purpura (ITP) is an immunological disease associated
      with pregnancy; it is difficult to control when there is not an adequate response
      to the treatment mainly with prednisone (refractory). When this problem occurs
      there are other ways to treat it: monthly pulses of dexamethasone (oral or
      intravenously), administration of gamma globulin or anti D and occasionally to
      perform a splenectomy. Three cases of refractory ITP and pregnancy are presented
      using different treatment in each case: Case 1 hyperimmune gammaglobulin; case 2
      platelets by transfusion and in case number 3 monthly dexamethasone oral pulses.
      In the case treated with hyperimmune gammaglobulin the maternal response was
      acceptable but neonatal demise occurred due to hemorrhage; in the treated with
      platelets transfusion, there were maternal and fetal deaths; the best results
      were obtained with the administration of dexamethasone monthly, in this way we
      were able to reach the term of the pregnancy with good results for mother and
      neonate. The importance of early diagnosis is imperative and initiating the
      adequate treatment that according to our results would be dexamethasone pulses;
      the use of hyperimmune gammaglobulin in restricted due to high cost, and the
      platelets transfusion would be indicated only in cases of severe
      thrombocythopenia, imminence of hemorrhage or if a surgical procedure has to be
      done. An extensive review of the literature is done.

PMID- 9273338
TI  - [Uterine arteriovenous malformations, Review of the literature].
AB  - Uterine arteriovenous malformation (AVMs) are fairly rare. Seventy four cases
      have been reported in the medical literature. The clinical presentation of this
      entity is quite diverse. The approach to uterine AVM requires clinical alertness
      and to make the diagnosis a high index of suspicion is required. Prompt treatment
      is often essential. This article reviews the entire literature on uterine AVM
      emphasizing the various clinica presentations and treatment modalities available
      for the gynecologist.

PMID- 9273339
TI  - [Immunopathology of early abortion: current status].
AB  - We reviewed the bibliography concerning the roles involved in the immunological
      mechanism related to the etiology of miscarriage, pointing out the main theories
      specially related to the Major Histocompatibility Complex and TLX antigen all
      together are beginners of the antiidiotype reaction in order to avoid having a
      miscarriage. It is mentioned that the blocking antibodies, suppressor cells and
      interleukines arrest the citotoxic immune mechanism against the fetal allograft.
      The new therapeutic approach is mentioned.

PMID- 9273340
TI  - [Interaction of endogenous opioid peptides with the function of the hypothalamo
      hypophyseal-testicular axis].
AB  - Since the discovery of endogenous opioid peptides and opioid receptors in the
      brain, their has been considerable interest in their possible role in a variety
      of physiological and pharmacological processes. The endogenous opioids and opiate
      active substances have been clearly implicated in the regulation of male
      reproductive function. It has been demonstrated that opioid peptides inhibit
      gonadotropin and TSH secretion and enhance PRL, GH and ACTH. It is believed that
      opioids elicit their action at the hypothalamic level, most likely by modulating
      the liberation of hypothalamic releasing or inhibiting factors. In healthy male
      adults the endogenous opioid peptides (EOP) produce a decrease in serum levels of
      gonadotropins. Administration of specific opiate antagonists decreases
      luteinizing hormone (LH) release and increases the frequency and amplitude of the
      LH pulses. The effects of EOP and specific opiate antagonists are altered in some
      hypothalamic-hypophysis-testis axis pathologies.

PMID- 9273341
TI  - [The Munster Prognosis Score (MPS)--prognostic validity of a practical instrument
      for prediction of progress in schizophrenic psychosis].
AB  - The prognostic validity of a short and easy to handle prognostic instrument
      (Munster prognosis score, MPS) for schizophrenic patients is proved in this
      study. The MPS consists of 4 items: number of hospitalisations, stability of
      course of illness in the last year, premorbid development, and stability of
      psychosocial environment. Each item has to be rated as favourable or
      unfavourable. With three or four favourable ratings the prognosis is good,
      otherwise bad. The interrater reliability proved with 50 DSM-III schizophrenic
      patients had a kappa of 0.84, which is sufficient. In an 8-years follow-up with
      66 DMS-III schizophrenic outpatients, the MPS had a comparably good prognostic
      validity according to the Strauss-Carpenter scale and the Philips scale in
      respect of the total symptom score (AMDP) and psychosocial functioning (GAS).
      According to prognosis of rehospitalisations, the MPS was as good as the SCS, and
      both were better than the Phillips scale.

PMID- 9273342
TI  - [The forensic-psychiatric evaluation of young persons in accordance with 105 JGG
      between punishment and therapeutic help].
AB  - 105 of the the German Jugendgerichtsgesetz (JGG, law on criminal cases involving
      offenders between 14 and 17 years of age) allows the use of this special law also
      for offenders between 18 and 21 years of age if they can be considered juveniles
      with regard to their personal development or the type of crime they have
      committed. Assessment of the "maturity" of young people in this age group has
      been the subject of great controversy in forensic psychiatry since the first JGG
      went into effect in 1953. In spite of numerous attempts to operationalize the
      term "Jugendlicher", for example in the Marburg guidelines, it has not yet been
      possible to establish clear-cut criteria defining the characteristics of those
      who are juveniles in the sense of the JGG. Neither child and adolescent
      psychiatry nor criminal law nor criminology has provided an adequate basis for
      such a definition. The wide range of discretionary decisions in forensic
      psychiatry and the associated lack of legal uniformity may, however, be a
      necessary prerequisite for an adequate assessment of an individual case. Although
      the chances of a change in criminal law governing those between 18 and 21 are
      small, creation of a law specifically for this age group, with a separation of
      the educational-therapeutic aspects from the punishment aspects, could be a great
      help to those preparing expert opinions in forensic psychiatry and to the
      juvenile courts because it would necessitate greater clarity in decisions
      relating to this group of offenders. Elimination of Section 105 JGG and the
      subsequent use of either general criminal law or that governing those under age
      18 only, which has been proposed repeatedly, is not recommended.

PMID- 9273343
TI  - [A rare case of psychogenic dysarthrophonia or a complex dyskinesia of the
      pharynx?].
AB  - We present the symptomatology of a complex articulation-related dyskinesia of the
      pharynx with intermittent functional velopharyngeal insufficiency. It became
      permanent gradually after a writer's cramp had remitted without therapy. No final
      nosologic assignment can be made on the basis of the described observations in
      the individual case. The development of the disease in the 56-year old male
      patient ended in occupational disability. It suggests manifestation of
      psychopathological events in the patient's life history of threshold situations
      by premorbid psychic vulnerability. The possibility of the etiopathologic
      interaction of emotional and neurological factors cannot be excluded. However,
      therapy with local botulinum toxin injections proved to be just as unsuccessful
      as logopedic treatment.

PMID- 9273345
TI  - [Hemi-neglect versus hemianopia. Differential diagnosis].
AB  - Neglect and hemianopia represent frequent disorders in brain damaged patients.
      Differential diagnosis of both disorders may be difficult since both may present
      in diagnostic tests and daily life as a failure to perceive or react to stimuli
      in the contralesional hemispace or hemifield. The present paper summarizes
      several useful techniques in order to achieve a correct distinction. After a
      short review of the clinical phenomenology of hemianopia and -neglect the
      following topics are described: (1) subjective complaints and awareness of
      deficits (2) aetiology and lesion localisation, (3) uni-versus multimodal
      deficits; (4) extinction, (5) drawing from memory; (6) visual-spatial disorders;
      (7) line bisection, (8) effectiveness of attentional "cueing" strategies; (9)
      specific perimetric techniques; (10) visual evoked potentials and eye movement
      registration. The differences between hemianopia and -neglect are contrasted for
      all these topics. Taken all these possible features together the association
      and/or dissociation of hemineglect and postchiasmatic scotomata can efficiently
      be diagnosed. The results are summarized in a table at the end of the paper.

PMID- 9273344
TI  - [Anticonvulsant treatment in old age--principles and differential indications].
AB  - When administering anticonvulsive drugs to the elderly, a number of peculiarities
      should be taken into consideration. Age-related changes in pharmacokinetics and
      drug interactions can make such treatment a complicated issue. Some of the side
      effects which hardly play a role among younger patients can lead to fatal
      consequences among the elderly. Both phenytoin (PHT), if submitted intravenously
      (but not in oral form), and carbamazepine (CBZ) may cause life-threatening
      cardiac arrhythmias. Valproate (VPA), otherwise well tolerated, seems to be less
      effective than CBZ and PHT in partial seizures. Cognitive dysfunction is a known
      side effect of barbiturates, but also seems to occur among the other drugs of
      first choice. In contrast to a widely held opinion, VPA, CBZ and PHT hardly
      differ in their effect on cognitive function if administered correctly.

PMID- 9273346
TI  - Immunological Approaches to Tumor Therapy. Proceedings from the III International
      Meeting on Idiotypic Network and Tumor Therapy by Gene Therapy, Drug Targeting,
      Vaccination, and Photodynamic Therapy. Bonn, Germany, February 29-March 2, 1996.

PMID- 9273347
TI  - Practical Issues in Using Olanzapine. Proceedings of a symposium. Boston,
      Massachusetts, August 1-3, 1996.

PMID- 9273348
TI  - Ingenious use of prosthesis in China.

PMID- 9273350
TI  - References, copyright and plagiarism.

PMID- 9273349
TI  - Keith Roberts Porter: 1912-1997.

PMID- 9273351
TI  - Stochastic behavior of ion channels in varying conditions.
AB  - The opening and closing of a single ion channel can be described as the
      aggregation into two sets of states, open and shut, of an underlying Markov
      process with a finite number of states. In this paper we consider an
      inhomogeneous process due to changing physical conditions, in particular a pulse
      of activity in which the transition rates during the pulse differ from those
      obtaining both before and after the pulse. Outside the pulse the chain contains
      an absorbing shut subset, so that no activity is observed before the pulse and
      almost surely, at most a finite number of openings are generated by the pulse. We
      consider, in particular, the probability distribution of first latency (the time
      to first opening) and the distribution of the total activation time. We take into
      account the phenomenon of time-interval omission, when short open or shut times
      fail to be observed.

PMID- 9273352
TI  - Special issue in honour of Tikvah Alper (1909-1995).

PMID- 9273353
TI  - The scrapie enigma: insights from radiation experiments. 1993.

PMID- 9273354
TI  - Surfactant and acquired lung diseases.

PMID- 9273355
TI  - Against nonscientific treatments.

PMID- 9273356
TI  - Complementary medicine: from quackery to science?

PMID- 9273357
TI  - Cyclin D1/PRAD1 as a central target in oncogenesis.

PMID- 9273359
TI  - Functional impairment of bronchoalveolar lavage phospholipids in early
      Pneumocystis carinii pneumonia in rats.
AB  - Surfactant abnormalities may contribute to the impairment of gas exchange
      observed in Pneumocystis carinii pneumonia. Analysis of rat bronchoalveolar
      lavage (BAL) lipid extracts from normal controls, steroid controls, trimethaprim
      sulfamethoxazole (TMP-SMX) controls, TMP-SMX/P. carinii pneumonia controls, and
      P. carinii pneumonia animals reveal similar total phospholipid and total protein
      levels. However, there was a marked reduction in phosphatidylglycerol (PG) from
      the BAL of P. carinii pneumonia rats as compared with control animals, with a
      decrease from 4.91 +/- 1.29 nmol/mg protein to 0.46 +/- 0.57 nmol/mg protein
      (p<0.05) and a decrease, as a percent of total phospholipids, from 7.7% +/- 0.88%
      to 0.91% +/- 0.59% (p<0.001). Furthermore, in vitro surface activities of BAL
      lipid extracts from control and P. carinii pneumonia rats revealed minimum
      surface tension increases from 9.38 +/- 1.71 mN/m in controls to 16.36 +/- 0.83
      mN/m in P. carinii pneumonia rats (p<0.05) and likewise maximum surface tension
      increases from 22.14 +/- 4.34 mN/m to 38.57 +/- 2.07 mN/m (p<0.01). Of interest,
      the surface activity of PG-deficient P. carinii pneumonia BAL lipid extracts is
      completely restored to that of normal controls by the addition of exogenous PG.
      These findings suggest that a functionally abnormal surfactant occurs in P.
      carinii pneumonia and that this may account, in part, for the impairment of gas
      exchange observed in this disorder.

PMID- 9273358
TI  - Molecular cloning and expression of a recombinant Aspergillus fumigatus protein
      Asp f II with significant immunoglobulin E reactivity in allergic
      bronchopulmonary aspergillosis.
AB  - The cDNA of Aspergillus fumigatus encoding an allergen was cloned and expressed
      in Escherichia coli. The 987 bp long cDNA clone expressed a recombinant protein
      Asp f II of 34 kd. This protein exhibited binding to immunoglobulin E (IgE) in
      the serum samples from patients with allergic bronchopulmonary aspergillosis
      (ABPA). The patients with ABPA and central bronchiectasis demonstrated high
      levels of serum IgE antibodies, whereas patients with ABPA without central
      bronchiectasis, patients with asthma and Aspergillus skin test reactivity but no
      evidence of ABPA, and patients with aspergilloma showed only low levels of IgE
      antibody to Asp f II. In two-dimensional electrophoresis, a native antigen
      electroeluted from an A. fumigatus culture filtrate antigen preparation showed an
      isoelectric point and molecular weight similar to that of Asp f II. In a
      competitive enzyme-linked immunosorbent assay (ELISA), the IgE antibody
      reactivity of Asp f II with patient serum samples could be significantly
      inhibited by culture filtrate antigens of A. fumigatus. These results indicate
      that Asp f II has immunologic reactivities comparable to those of native A.
      fumigatus antigens. The recombinant Asp f II can be expressed in E. coli in large
      quantities and should prove useful as a standardized allergen for sensitive and
      specific immunodiagnosis of ABPA, especially in patients with central
      bronchiectasis.

PMID- 9273360
TI  - Role of iron in the potentiation of anthracycline cardiotoxicity: identification
      of heart cell mitochondria as a major site of iron-anthracycline interaction.
AB  - The role of iron in anthracycline toxicity was studied in rats in vivo in intact
      animals and in vitro in heart cell cultures. In animals treated with 8 mg/kg
      doxorubicin, iron loading resulted in severe weight loss and a twofold increase
      in rate of mortality. Studies in cultured heart cells aimed at defining the
      subcellular target of interaction between iron and anthracycline toxicity showed
      no evidence of anthracycline-induced damage to sarcolemmal thiolic enzymes
      represented by 5'-nucleotidase and only a limited increase in lysosomal fragility
      as monitored by an increase in beta-hexosaminidase activity in cell homogenates
      and its release into the culture medium. By contrast, doxorubicin treatment
      resulted in a marked inhibition of mitochondrial function as monitored by a
      decrease in carbon 14-labeled palmitate utilization, to 33% +/- 4% of controls,
      and prior iron loading resulted in a further decrease in palmitate utilization,
      to 18% +/- 3% of controls. Conversely, iron-chelation treatment by either
      deferoxamine or deferiprone (L1) eliminated the harmful effects of iron loading
      and resulted in a partial inhibition of doxorubicin toxicity in both normal and
      iron-loaded cells. Our studies represent the first demonstration in intact
      animals of the potentiation of anthracycline toxicity by iron overload. They also
      indicate that mitochondria represent an important target of combined iron
      anthracycline toxicity. These observations provide new insights into the
      mechanism of anthracycline cardiotoxicity and may be useful in developing better
      strategies for tumor therapy.

PMID- 9273361
TI  - Neutrophil adherence to and migration across monolayers of human peritoneal
      mesothelial cells. The role of mesothelium in the influx of neutrophils during
      peritonitis.
AB  - Increased adherence to and subsequent migration of leukocytes across cultured
      human peritoneal mesothelial cell monolayers takes place after pretreatment of
      the mesothelial cells with interleukin-1beta. The contribution of the leukocyte
      beta2 integrins (CD11/CD18) and the mesothelial adhesion protein intercellular
      adhesion molecule-1 (ICAM-1) and the role of the cytokines interleukin-8,
      platelet-activating factor (PAF), and transforming growth factor-beta (TGF-beta)
      were studied in a three-dimensional model system for neutrophil-mesothelial
      monolayer interaction. Polymorphonuclear leukocytes (PMNs) showed minimal
      adherence to and migration across unactivated mesothelial monolayers, despite an
      extensive amount of ICAM-1 on the mesothelial membrane. Pretreatment of the
      monolayers with rIL-1beta induced enhanced PMN adherence to the mesothelial
      monolayer together with a further increase in ICAM-1 expression on the
      mesothelial membrane. PMN migration was observed across rIL-1beta-activated
      mesothelial cell (MC) monolayers whenever cytokines secreted by the MCs were
      present during migration. Monoclonal antibody (mAb) R6.5 against ICAM-1 and mAb
      CLB-LFA1/1 against CD18 both reduced the migration of PMNs across mesothelial
      monolayers with a predominant inhibitory effect of CLB-LFA1/1, indicating a
      significant role of the beta(2) integrins of PMNs in this process. Interleukin-8
      was the major cytokine synthesized by the MCs to stimulate the migration of PMNs;
      both PAF and TGF-beta had a more modest role in our system. Adherence of PMNs to
      MC monolayers was not dependent on these latter cytokines. Neuraminidase did not
      have any effect, indicating that selectins were not involved in the adherence
      process. rIL-1beta-pretreated MCs induced a rapid increase in intracellular Ca2+
      in PMNs; actinomycin D blocked this effect and was also able to prevent adhesion
      of neutrophils to activated MC monolayers. Neutrophil migration across activated
      cultured MCs is thus a cascade of events in which the MCs are actively involved.

PMID- 9273362
TI  - Reversal by high-density lipoprotein of the effect of oxidized low-density
      lipoprotein on nitric oxide synthase protein expression in human platelets.
AB  - Oxidized low-density lipoproteins (ox-LDLs) induce vasoconstriction and platelet
      activation, and high-density lipoproteins (HDLs) reverse these effects of ox-LDL.
      To determine the involvement of the L-arginine-nitric oxide (NO) pathway in the
      effects of lipoproteins on platelets, washed human platelets were incubated with
      native-LDL, ox-LDL, or HDL plus ox-LDL, but not native LDL, potentiated thrombin
      induced platelet aggregation and carbon 14-labeled serotonin release, and these
      effects of ox-LDL were blocked by pretreatment of platelets with HDL. Incubation
      of ox-LDL with platelets resulted in reduction in the uptake of tritiated L
      arginine by intact platelets and in NO synthase activity in platelet lysate.
      These effects of ox-LDL on platelet NO synthase activity were also reversed by
      pretreatment of platelets with HDL. Western blot analysis demonstrated about a
      50% reduction in the expression of NO synthase protein in platelets treated with
      ox-LDL. Whereas HDL alone had no effect on NO synthase protein expression, it
      blocked the decrease in NO synthase expression caused by ox-LDL. Thus ox-LDL
      stimulates platelet function primarily by diminishing NO synthase expression, and
      this effect of ox-LDL can be blocked by pretreatment of platelets with HDL.

PMID- 9273363
TI  - Measurement of human platelet microaggregates by a new method: ultrasonic
      interferometry.
AB  - We have adapted the ultrasonic interferometry technique (Echo-Cell), which was
      initially designed to study red blood cell aggregation and agglutination, to the
      detection of human platelet microaggregates. The experimental parameter chosen
      was the slope of the signal over the first 5 minutes of sedimentation. We
      compared our new method with the conventional aggregometry for the measurement of
      aggregates after thrombin-, collagen-, and epinephrine-induced platelet
      activation. Under these conditions we demonstrated the particular sensibility of
      the present method in detecting small platelet aggregates induced in the first
      phase of aggregation and formed by low concentrations of agonists. Furthermore,
      as an illustration of this method, we showed an inhibition of the formation of
      thrombin-induced platelet aggregates in a concentration-dependent manner by the
      well known antagonist arginine-glycine-aspartic acid-serine with a median
      inhibitory concentration of 0.4 micromol/L, which is 30 times lower than the
      median inhibitory concentration found by aggregometry.

PMID- 9273365
TI  - An immunocytochemical study of H+ ATPase in kidney transplant rejection.
AB  - Kidney transplant rejection may be accompanied by defective urinary
      acidification. Its pathogenesis is unknown. There are shared histologic features
      between kidney transplant rejection and the distal renal tubular acidosis (RTA)
      of Sjogren syndrome, which led us to hypothesize that deficient collecting duct
      H+ adenosine triphosphatase (ATPase) expression--which is lacking in the RTA of
      Sjogren syndrome - may cause the RTA of kidney transplant rejection. Six kidney
      transplant recipients with biopsy evidence for rejection and two control subjects
      were studied physiologically and by immunohistochemistry. We found defective
      urinary acidification in all 6 kidney transplant patients. Ammonium excretion was
      diminished in relation to the degree of azotemia. There was an abnormal response
      to furosemide in all 6, suggesting distal tubular dysfunction. Distal H+ ATPase
      staining was reduced in relation to the degree of azotemia, although it was not
      totally absent even in the worst case. This was paralleled by the urinary PCO2
      response. Both control subjects had good urine PCO2 and H+ ATPase staining and
      adequate urine pH response to furosemide. They had reduced urinary ammonium (NH4)
      concentrations in relation to modest azotemia. We conclude that kidney transplant
      rejection may be accompanied by defective urinary acidification, which is not
      primarily due to a lack of H+ ATPase. The RTA of kidney transplant rejection
      appears to result from defective ammonium excretion, generalized distal tubular
      malfunction, and--in severe cases--from a reduction in distal nephron H+ ATPase
      expression.

PMID- 9273364
TI  - Evaluation of 13CO2 breath tests for the detection of fructose malabsorption.
AB  - Breath hydrogen (H2) studies have made clear that small intestinal absorption of
      fructose is limited, especially in toddlers. Malabsorption of fructose may be a
      cause of recurrent abdominal pain and chronic nonspecific diarrhea (toddler's
      diarrhea). Fructose absorption is facilitated by equimolar doses of glucose and,
      as we have found, amino acids (especially L-alanine); the mechanism underlying
      this effect remains unclear. To study fructose absorption in a more direct way,
      we combined breath H2 studies with breath 13CO2 studies. Gastric emptying was
      studied by using L-glycine-1-13C in 4 children from 12.1 to 16.0 years of age.
      After 25 gm of fructose and 27.5 gm of glucose, when given together, gastric
      emptying was significantly (p<0.05) slower than with either sugar alone. In a
      second series of experiments, 5 children from 12.0 to 15.9 years of age were
      tested with 25 gm of fructose, alone and with equimolar doses of glucose and L
      alanine, and 4 younger children from 3.1 to 6.1 years of age were tested with 2
      gm/kg (max 37.5 gm) fructose, alone or with an equimolar dose of L-alanine. All
      fructose solutions were enriched with 15 mg of D-fructose-13C-6. In all 9
      children, fructose was malabsorbed as judged by breath H2 increases > or = 20
      ppm, and the addition of glucose or L-alanine resulted in significantly lower
      breath H2 increases (p < or = 0.005 for glucose, p < or = 0.001 for alanine). In
      contrast, the addition of alanine or glucose did not change the pattern of breath
      13CO2 excretion in the 5 older children, whereas in the 4 younger children (with
      relatively higher doses), L-alanine addition resulted in significantly lower
      increases in breath 13CO2. In the latter group, for each time point, breath H2
      and 13CO2 concentrations after fructose were compared with those after fructose
      plus L-alanine; in 20 out of 24 points, both H2 and 13CO2 were higher after
      fructose. These results suggest that 13CO2 not only originated from the oxidation
      of absorbed substrate but also, at least in part, from colonic bacterial
      metabolism. For the detection of [correction of or] fructose malabsorption--as
      opposed to, for instance, lactose--the 13CO2 breath test seems to be of limited
      value.

PMID- 9273366
TI  - Prosthetic component failures in hip arthroplasty surgery.
AB  - A survey was conducted of the entire membership of the American Association of
      Hip and Knee Surgeons to determine their experience with total hip arthroplasty
      (THA) device-related failures. Forty-seven percent of the membership reviewed
      their preceding 5-year clinical experience and returned the survey instrument.
      The aggregate 5-year volume encompassed experience with more than 60,000 hip
      arthroplasties. The median 5-year experience per respondent was 200 metal-based
      sockets and 214 metal stems. The frequency distribution of the number of hip
      arthroplasties per respondent was skewed to the right, with fewer surgeons
      reporting the higher volumes of arthroplasties. In aggregate, 60,115 of the
      acetabular components used were metal backed. Nonmetal acetabular component usage
      totaled 3,219. Complete polyethylene failure was defined as fracture or complete
      wear through of the polyethylene portion of the component. Complete polyethylene
      failure was seen in 172 metal-backed sockets (29/10,000). Seventy-seven all
      polyethylene sockets had complete polyethylene failure (239/10,100). A total of
      87 THAs were revised for modular acetabular dissociations for a dissociation rate
      of 15/10,000. In aggregate, 64,483 metal-stemmed components were used. Femoral
      stem fractures occurred in 172 for a rate of 27/10,000. A total of 56,965
      metallic femoral components were reported as being modular. Dissociation between
      the femoral head and neck was uncommonly seen (3/10,000). Use of ceramic femoral
      heads was low (5,023); however, a total of 11 ceramic head fractures were revised
      in the 5-year period for a failure rate of 22/10,000. The risks of catastrophic
      prosthetic THA failure are low but vary according to hip component and the
      manufacturer of the part.

PMID- 9273367
TI  - Effect of improved cementing techniques on the longevity of fixation in revision
      cemented femoral arthroplasties. Average 8.8-year follow-up period.
AB  - Forty-six revision cemented femoral arthroplasties in which second-generation
      cementing techniques were used have been reviewed. After an average follow-up
      period of 8.8 years, 91% of the femoral components remained in place and 87%
      remained well fixed. Only 7% were rerevised for aseptic loosening. These results
      demonstrate a marked improvement over those of first-generation cementing
      techniques.

PMID- 9273368
TI  - Cemented collarless (Exeter-CPT) versus cementless collarless (PCA) femoral
      components. A 2- to 14-year follow-up evaluation.
AB  - The purpose of this study was to compare the intermediate results of total hp
      arthroplasty with a cemented, collarless, femoral prosthesis design (Exeter,
      Howmedica, Middlesex, UK and CPT, Zimmer, Warsaw, IN) with those of a cementless,
      collarless, porous-coated femoral component (PCA, Howmedica). A total of 151 hips
      in 128 patients were reviewed. In the cemented group, 85 Exeter-CPT prostheses
      were used in 71 patients with an average follow-up period of 6.5 years. In the
      uncemented group, 66 PCA prostheses were placed in 57 patients with an average
      follow-up period of 7 years. Harrington hip scores improved from 50.1 to 80.7 for
      the PCA group and from 49.5 to 87.3 for the Exeter-CPT group. The patient
      satisfaction rates were 89 and 96%, respectively. Sixty-eight patients with
      Exeter or CPT prostheses had excellent function and no significant thigh pain
      after 2 years. One Exeter stem was revised 10 years after the primary surgery
      because of aseptic osteolysis due to cement defect. Two Exeter sockets were
      revised because of aseptic loosening. In the PCA group, the incidence of thigh
      pain that persisted beyond 2 years was 39.4%, and there were high incidences of
      distal cortical hypertrophy (66.6%) and bead loosening (45.5%). Sixteen hips were
      revised for aseptic stem loosening of the socket. The cementless ingrowth stems
      failed earlier (around 5 years), whereas the cemented stems continued to perform
      well past 14 years. In this study, the cemented, collarless, tapered, femoral
      prosthesis gave results superior to those of the uncemented collarless, porous
      coated anatomic design at an average follow-up period of 7 years (range, 2-14
      years).

PMID- 9273369
TI  - Total knee arthroplasty in a group of patients less than 45 years of age.
AB  - The long-term follow-up evaluation of total knee arthroplasty (TKA) in patients
      under age 45 is reviewed. One hundred three knees in 67 patients who had an
      average follow-up period of 7.2 years were retrospectively reviewed. Fifty-eight
      percent of the patients had rheumatoid arthritis, and 29% had juvenile rheumatoid
      arthritis. Thirteen percent of the patients had post-traumatic arthritis,
      avascular necrosis, hemochromatosis, or lupus. The results demonstrate that the
      success of TKA in this patient population are comparable to those for TKA in the
      elderly.

PMID- 9273370
TI  - Comparison of cemented and cementless total hip arthroplasty in patients with
      bilateral hip arthroplasties.
AB  - A consecutive series of 36 patients underwent primary cemented total hip
      arthroplasty followed by primary cementless total hip arthroplasty of the
      contralateral hip. Clinical pain scores between the cementless and cemented hips
      were not different. Subjectively, patients either had no preference or preferred
      the cementless side. Comparison of results in the same patient eliminates
      variability introduced by differences in sex, weight, comorbidities, bone
      quality, and activity level. Control of these factors permits more meaningful
      comparison of the type of fixation.

PMID- 9273371
TI  - Influence of surgical approach on dislocations after Charnley hip arthroplasty.
AB  - Dislocations occurring in 3,199 Charnley total hip arthroplasties in two
      orthopaedic centers between 1979 and 1991 performed by either the
      transtrochanteric or posterior approach were studied. The incidence of
      dislocation within 2 years of surgery (2.8%), as well as the overall frequency
      (3.4%), did not differ between the two centers. Regardless of approach, there was
      a higher risk of dislocations for patients with osteoarthrosis. A logistic
      regression analysis, reflecting the differences in preoperative hip diagnoses and
      sex, indicated that the dislocation rate was not influenced by the surgical
      approach. More early dislocations were documented after the posterior approach,
      but without increases in the rates of recurrence or revision. Arthroplasties
      performed by less experienced surgeons through the posterior approach resulted in
      more dislocations.

PMID- 9273372
TI  - Early failure of the femoral component in unicompartmental knee arthroplasty.
AB  - Unicompartmental knee arthroplasty has been proposed as treatment for
      unicompartmental arthritis. Overall, results have been satisfactory, with
      occasional failures of tibial component fixation. Short-term loosening of the
      femoral components in unicompartmental knee arthroplasty that required revision
      to total knee arthroplasty is reported. All patients presented with pain and
      instability of the knee, with loosening confirmed radiographically and at
      revision surgery. The Porous-Coated Anatomic femoral component (Howmedica,
      Rutherford, NJ) was biomechanically tested after being implanted in cadaver
      limbs. Cyclic loading in flexion and extension under physiologic loads resulted
      in implant failure. The mode of failure was rocking in the sagittal plane, which
      corresponds to the clinical findings. The femoral implant design consists of an
      angled bone-implant interface with straight arms, which causes shear at the bone
      prosthesis interface did not loosen under identical biomechanical testing in
      paired knees. It was concluded that the Porous-Coated Anatomic femoral component
      has an unacceptably high early clinical loosening rate, confirmed by comparative
      biomechanical testing.

PMID- 9273373
TI  - The Wisconsin noncemented femoral stem. A prospective study with 5 to 9 years of
      follow-up evaluation.
AB  - In an attempt to decrease aseptic loosening, total joint components are now being
      used without cement. Most components are designed to achieve fixation
      biologically. The radiographic results of 144 primary uncemented total hip
      arthroplasties and the clinical results of 89 arthroplasties that were performed
      using a proximally porous-coated titanium alloy femoral stem between November
      1983 and June 1989 are reported. On the acetabular side, a threaded component or
      a hemispherical porous-coated component was used. The patients were followed
      prospectively for 5 to 9 years postsurgery. During the study period, the threaded
      acetabular component had a high failure rate. Because it was not possible to
      determine accurately from which component a particular sign or symptom arose,
      clinical analysis was restricted to only those hips without a failed or revised
      cup. Eighty-nine hips in 71 patients with a minimum follow-up period of 5 years
      were available for clinical review. Radiographic review of the femoral stem was
      completed on all hips with 5 or more years of radiographic follow-up evaluation
      regardless of the status of the acetabular component. One hundred twelve hips in
      85 patients were analyzed radiographically. At a latest mean follow-up period of
      6.7 years, the mean Iowa hip score was 91.4 +/- 8.0 with a 5.4% incidence of
      thigh pain. Throughout the follow-up period, the patients with thigh pain had a
      statistically lower mean Iowa pain subscore when compared with those patients
      without thigh pain (P=.0001). Endosteal erosion was seen in two hips (1.8%) and
      longitudinal loss of the medial neck greater than 2 mm was noted in two hips. One
      femoral stem was revised for aseptic loosening. The clinical results of this
      femoral stem equal or exceed the published accounts of other arthroplasties. The
      results indicate that the stem is associated with good clinical results, minimal
      bone loss, and little osteolysis. Continued follow-up evaluation of patients with
      this femoral stem is necessary to assess the durability of these encouraging
      results.

PMID- 9273375
TI  - Measurement accuracy in acetabular cup wear. Three retrospective methods compared
      with Roentgen stereophotogrammetry.
AB  - The accuracy of three methods (the simple and noncomputerized Scheier-Sandel and
      Charnley-Duo methods and the computerized Ein Bild Roentgen Analyse [EBRA]
      method) for retrospective wear measurements of the acetabular cup from standard
      pelvis radiographs was studied. Measurements on 13 hip prostheses were compared
      with those obtained by roentgen stereophotogrammetry analysis. The Scheier-Sandel
      method had the lowest accuracy and the EBRA method had the best accuracy. The
      Charnley-Duo method was almost as good when starting analysis 3 months after
      surgery and is easier to use. The EBRA method is useful for accurate measurements
      on a small number of patients; the Charnley-Duo method is recommended for
      clinical wear studies on a larger number of patients.

PMID- 9273374
TI  - Intracapsular pressure and pain in coxarthrosis.
AB  - Intracapsular hip pressure was measured before surgery in 17 patients (18 hips)
      with coxarthrosis. The results were correlated to pain as registered on a visual
      analog scale. With the hip in extension, the pressure was 49.5 mmHg (SD, 40.2);
      in 45 degrees of flexion, it was 21.3 mmHg (SD, 14.6); in extension and inward
      rotation, it was 105.7 mmHg (SD, 76.0); and in extension and outward rotation, it
      was 40.8 mmHg (SD, 32.0). A small amount, 0.7 mL (SD, 1.14), of joint fluid was
      aspirated following pressure registration. Pressure correlated significantly to
      pain at night, when starting to walk, and on walking. It is suggested that the
      increase in intracapsular hip pressure is a cause of pain in coxarthrosis, with
      subsequent limitation of movement and joint contracture.

PMID- 9273376
TI  - Intercondylar distal femoral fracture. An unreported complication of posterior
      stabilized total knee arthroplasty.
AB  - In an attempt to study the incidence of intraoperative femoral intercondylar
      fractures, two large series of posterior-stabilized total knee arthroplasty (TKA)
      systems were reviewed. Eight hundred ninety-eight nonconsecutive primary
      posterior-stabilized TKAs were compared with a second nonconsecutive series of
      532 posterior-stabilized TKAs. Unique to the secondary TKA system is an
      intercondylar sizing guide to aid in verification of the intercondylar resection
      size. In the initial series, 40 distal femoral intercondylar fractures were noted
      (rate = 1:22; nondisplaced, 35; displaced, 5). In the secondary series, one
      displaced distal femoral intercondylar fracture occurred (rate = 1;532). The
      difference in the rate of fracture between the two populations was statistically
      significant (P<.001). Intraoperative distal femoral intercondylar fracture
      represents a potential complication of TKA and can be avoided with careful
      resection technique and size verification. No change in the postoperative
      rehabilitation program is required, however, for those patients identified with
      nondisplaced and intraoperative-stabilized displaced distal femoral intercondylar
      fractures.

PMID- 9273377
TI  - Effect of tibial component position on patellar strain following total knee
      arthroplasty.
AB  - Patellar fracture following total knee arthroplasty has been related to component
      alignment and tibiofemoral joint-line position. The purpose of this study was to
      determine the effect of anteroposterior displacement of the tibial component and
      inferosuperior displacement of the tibiofemoral joint line on patellar strain
      following total knee arthroplasty with a cruciate-substituting design. Patellar
      strain increased (decreased) with anterior and inferior (posterior and superior)
      displacement. When averaged across all flexion angles, the strain changed
      approximately 1.7%/mm of anteroposterior displacement and 1.0%/mm of
      inferosuperior displacement. For individual specimens, changes in strain as high
      as 3.2%/mm of inferosuperior displacement of the joint were seen. These changes
      in strain may be associated with changes in tibiofemoral joint-line position.
      These changes in strain may be a biomechanical indicator of the efficacy of
      retaining the preoperative position of the tibiofemoral joint line.

PMID- 9273378
TI  - Flexion space configuration in total knee arthroplasty.
AB  - Equal resection of the posterior femoral condyles combined with a 90 degree
      tibial resection results in a trapezoidal flexion space. Two groups of patients
      were studied; in one group, the flexion space was allowed to remain trapezoidal,
      whereas in the other group, the anteroposterior femoral resections were
      externally rotated to allow rectangularization of the flexion space. In the
      second group, the range of flexion was increased and the incidence of medial
      tibial pain and zone I radiolucencies decreased. Other than for knees in a
      hypervalgus position before surgery, the mean amount of rotation required was 3
      degrees +/- 0.2 degrees.

PMID- 9273379
TI  - Use of acetabular models in planning complex acetabular reconstructions.
AB  - The number of patients requiring revision total hip arthroplasty continues to
      increase each year. Accurate preoperative planning is a key factor in obtaining a
      good result. Radiographs provide little information concerning the actual extent
      of the acetabular defects. Computed tomography-generated models of the acetabulum
      can provide the surgeon with accurate information concerning the size and
      location of the defects. Evaluation of radiographs and models in 24 cases showed
      that radiographs alone failed to detect all 13 anterior wall defects (P < .001),
      8 of 18 posterior wall defects (44.4%, P < .001), and 8 of 19 segmental central
      defects (42%, P < .001), all of which were easily identified with the models.
      This study showed that preoperative planning based on the foam models accurately
      predicted the actual implant used in 22 of 24 cases (92%).

PMID- 9273380
TI  - Dislocation after bipolar hemiarthroplasty of the hip.
AB  - Although bipolar hemiarthroplasty of the hip is a frequently performed procedure,
      little information is available about the frequency of postoperative dislocation
      and its treatment. For this study, 1,934 hips treated consecutively with primary
      bipolar hemiarthroplasty were reviewed. A postoperative dislocation developed in
      29 patients (1.5%): during the first month after surgery in 24 patients and
      between 1 month and 5 years after surgery in five patients. Of the 29
      dislocations, 25 were successfully reduced with with routine closed methods.
      Among these 25 hips, 13 (52%) subsequently redislocated, and 7 of these required
      operative treatment for the recurrent dislocation. Dislocation after primary
      bipolar hemiarthroplasty is infrequent, can usually be reduced by routine closed
      methods, but is associated with a high rate of recurrent dislocation.

PMID- 9273381
TI  - Loose-hinge total elbow arthroplasty. An experimental study of the effects of
      implant alignment on three-dimensional elbow kinematics.
AB  - A previous study suggested that the kinematics of a loose-hinge total elbow
      arthroplasty (TEA) are those of a truly semiconstrained joint. This study
      addresses the effects of malposition of the implant. The three-dimensional elbow
      kinematics during simulated active motion were studied in six cadaver specimens
      using an electromagnetic tracking device. In addition to simulated active elbow
      flexion, flexion arcs were obtained under an elbow varus or valgus moment, to
      calculate the structural varus-valgus laxities. The results after four different
      Coondrad-Morrey TEA positions of implantation were compared with those of the
      intact elbow. The flexion-extension amplitudes were not significantly decreased
      after TEA implantation, except with external rotation of the ulnar component,
      which resulted in a loss of extension. In the intact elbow and after TEA
      implantation in any position, the mean varus-valgus deviations throughout elbow
      flexion were in a narrower range than the structural limits imposed by the
      ligaments (intact elbow) or the TEA hinge design. With internal malrotation of
      the humeral component over 10 degrees, however, the valgus structural limit was
      reached and, conversely, the varus limit with external rotation over 10 degrees.
      The clinical improvement observed with the semiconstrained TEA is derived from
      the benefits of the less constrained articulation. The proximodistal changes of
      TEA implantation have no consequence on the kinematic pattern. Rotational
      malpositioning of either humeral or ulnar component should be avoided, the first
      because it changes the kinematic pattern toward the structural limits of the
      implant and, therefore, may lead to excessive stresses at the bone-cement-implant
      interfaces and to early loosening, and the latter because it causes loss of
      extension.

PMID- 9273383
TI  - Total hip arthroplasty cemented femoral component distal stem centralizer. Effect
      on stem centralization and cement mantle.
AB  - The effectiveness, benefits, and potential risks of employing a total hip
      arthroplasty cemented femoral component distal centralizer were evaluated. First
      postoperative (6-week) radiographs of 100 primary hybrid total hip arthroplasties
      in consecutive groups of 50 patients without and 50 patients with a femoral stem
      distal centralizer were retrospectively reviewed. Femoral stems with a distal
      centralizer were more centralized within the femoral canal (center of stem tip to
      center of intramedullary canal: mean, 1.1 mm with a centralizer, 3.2 mm without;
      P<.0001) and more neutrally aligned (mean, 0.7 degrees valgus with a centralizer,
      1.3 degrees valgus without; P < .01). Femoral stems with a distal centralizer
      were less likely to have a cement mantle with suboptimal thickness, that is, less
      than 2 mm at the medial distal femoral stem (3 of 50 stems with a centralizer, 22
      of 50 stems without; chi-square, P<.0001). There were no complications, adverse
      effects on the cement mantle, radiographic evidence of loosening, or implant
      failures associated with the use of a distal centralizer, with a minimum follow
      up period of 2 years.

PMID- 9273382
TI  - Neural system of the human posterior cruciate ligament in osteoarthritis.
AB  - The purpose of this study was to quantify the neural elements in a group of
      posterior cruciate ligaments from osteoarthritic patients in comparison with
      normal subjects. Nine ligaments obtained from total knee arthroplasty procedures
      and five control ligaments from amputated limbs or fresh cadavers were stained
      with gold chloride. The percentage area occupied by the receptors and the neural
      network was determined by means of a computer-assisted image analyzer. A
      significant reduction of the neural elements was observed in the group of
      ligaments from osteoarthritic patients (0.44 +/- 0.132 SEM vs 0.958 +/- 0.13 SEM,
      P = .001). The loss of mechanoceptors and the consequent reduction of neural
      afferences may reduce the functional stability of the joint, participating in the
      osteoarthritic degenerative process.

PMID- 9273385
TI  - Closed reduction for total hip arthroplasty dislocation. The Tulsa technique.
AB  - A different technique for closed reduction of the dislocated total hip
      arthroplasty is described. The maneuver is effective and efficient, may be
      performed without an assistant, and reduces potential risks to the surgeon.

PMID- 9273384
TI  - Preliminary study of the effect of aging following irradiation on the wear of
      ultrahigh-molecular-weight polyethylene.
AB  - Several studies have indicated that degradation of ultrahigh-molecular-weight
      polyethylene following gamma irradiation in air adversely affects the mechanical
      properties of the material; however, it is not known how this subsequently
      affects its wear rate. Wear studies have therefore been performed on three groups
      of ultrahigh-molecular-weight polyethylene; unirradiated material, recently
      irradiated material (aged for 2 months), and aged irradiated material (aged for 5
      years). The aging took place in sterile packaging on the shelf. The wear studies
      were carried out on a tri-pin-on-disk wear tester, with a pin from each type of
      material being studied in each test. In each test the wear rate of the
      nonirradiated material was slightly lower than the 2-month-aged, irradiated
      material. The 5-year-aged, irradiated material had the highest wear rate, and
      this was significantly greater than that of the unirradiated material (P < .05).

PMID- 9273386
TI  - Symptomatic heterotopic ossification following total knee arthroplasty.
AB  - Heterotopic ossification has been reported to occur in less than 10% of total
      knee arthroplasties. When this condition has occurred, it has previously been
      reported either to be asymptomatic or to cause discomfort that resolves with the
      passage of time. This case report is the first to note persistent pain and
      snapping due to heterotopic ossification adherent to the distal femoral cortex
      that required surgical excision to relieve symptoms after total knee
      arthroplasty.

PMID- 9273387
TI  - Radiohumeral arthrodesis for salvage of failed total elbow arthroplasty.
AB  - Ulnohumeral arthrodesis is the standard technique for elbow fusion. The geometry
      and surface area of the distal humerus and proximal ulna enhance the chances of
      fusion while maintaining some wrist motion. A case of a patient with multiple
      failed elbow procedures in which the standard ulnohumeral fusion was not possible
      is presented. A radiohumeral arthrodesis was performed in an attempt to obtain a
      stable, nonpainful elbow. After complete healing of the fusion, the patient was
      able to use the arm for most functions. This technique is presented as an option
      for salvage failed elbow arthroplasty in the face of significant bone loss.

PMID- 9273388
TI  - Appositional bone bridging of primary gaps in the dome area of uncemented, porous
      acetabular components.
AB  - Reported here are two cases of primary hybrid arthroplasties using a cemented
      stem and an uncemented, porous acetabular component. Because of the configuration
      of the acetabula, a residual central gap remained after implantation of the
      socket. Unimpacted grafts were used to fill the spaces. The gaps, amounting to 4
      to 5 mm on the postoperative radiographs, had disappeared at the 30-40-month
      follow-up examination, with no radiolucent lines at the bone-implant interface.
      Both sockets were evaluated by roentgen stereophotogrammetric analysis for 2
      years, and by using this technique for detecting micromovements, central
      migration as a reason for the disappearance of the gaps was precluded. Bony
      apposition of primary gaps of up to 5 mm in the central area of well-fixed porous
      acetabular components seems possible.

PMID- 9273389
TI  - Total knee arthroplasty in the management of proximal tibial stress fractures.
AB  - Five patients with stress fractures of the proximal tibia adjacent to an
      arthritic knee joint were treated by resurfacing arthroplasty with intramedullary
      fixation of the fracture. All five fractures healed and limb realignment was
      achieved. The literature concerning proximal tibial stress fractures in relation
      to the arthritic knee and the management of this condition is reviewed.

PMID- 9273390
TI  - Assessment of the nutritional effects of olestra.

PMID- 9273391
TI  - [Pseudo-stroke: current views].

PMID- 9273392
TI  - [Tumor and inflammation markers in diagnosis of serous pleural exudate].

PMID- 9273393
TI  - [Osteoporosis].

PMID- 9273394
TI  - [Effects of disturbances of natural magnetic field of the Earth on melatonin
      production in patients with coronary heart disease].
AB  - The obtained results clearly evidence for the influence of magnetic disturbances
      and storms on melatonin production in patients with ischemic heart disease.
      Improvement of 24-hour rhythm of melatonin secretion during the period of
      magnetic disturbances says in favour of this influence while an overall fall of
      melatonin production during magnetic disturbances and storms is an apparent
      negative factor.

PMID- 9273395
TI  - [High-dose nitroglycerin in cardiogenic shock].
AB  - Effective hemodynamics was reestablished in 20 out of 22 patients with acute
      myocardial infarction or other heart diseases running in the presence of
      cardiogenic shock by isolated jet intravenous injection of nitroglycerin without
      vasopressors. 14 of them survived, whereas out of 17 controls treated with
      vasopressors alone 16 patients died. It is thought valid to start treatment of
      cardiogenic shock in elevated venous pressure with intravenous jet injection of
      nitroglycerin.

PMID- 9273396
TI  - [Pseudotumorous form of chronic tick-borne encephalitis].

PMID- 9273397
TI  - [Serum neopterin in hemorrhagic vasculitis].
AB  - Out of 12 patients with hemorrhagic vasculitis (HV) having the disease for 3-3.2
      years (5 males and 7 females aged 18-55 years, mean age 34 +/- 13.8 years) renal
      affection was found in 3 (25%) patients. Renal function was normal in all the
      patients. One patient had nephrotic and two had mixed nephritis. One patient had
      gastrointestinal lesions. Serum neopterin was measured by radioimmunoassay. Mean
      concentration of serum neopterin was significantly higher than in donors (9.15 +/
      6.82 nmol/l and 5.2 +/- 2.1 nmol/l, respectively). A high neopterin level was
      found in 2 (67%) of 3 patients with nephritis and in 1(11%) of 9 patients free of
      nephritis. Mean neopterin was significantly higher in 3 patients with renal
      disorders than in the comparison group. A positive correlation existed between
      neopterin level and the clinical activity index, ESR, IgA, IgG CIC
      concentrations.

PMID- 9273398
TI  - [Acute pneumonia in alcoholics: onset and course].
AB  - As indicated by the data on acute pneumonia (AP) analyzed from the case histories
      of chronic alcoholics who had died in the hospital for addicts, AP in alcoholics
      runs with scare symptoms in the absence of physical manifestations and takes a
      severe course. The authors provide recommendations on AP diagnosis and treatment
      in chronic alcoholics.

PMID- 9273399
TI  - [Sulphasalazine: a promising drug in rheumatology].

PMID- 9273400
TI  - [Essential hypertension or hypertensive disease? Classification problems].

PMID- 9273401
TI  - [Effects of becotide and becodisk glucocorticoid drugs on bronchial reactivity in
      patients with bronchial asthma].
AB  - Efficacy of inhalation corticosteroids becotide and becodisk was compared in 24
      patients with bronchial asthma. Becodisk has the advantage of not containing
      freon which irritates upper airways and bronchial mucosa. Clinical,
      allergological, bronchial resistance, provocative carbacholine tests, external
      respiration tests, peakflowmetry demonstrated that becodisk reduced the number of
      asthma attacks, lowered the need in inhalation sympathomimetics, improved
      external respiration function, decreased bronchial sensitivity to carbacholine.
      Determination of specific and nonspecific bronchial reactivity is thought
      essential in comparing efficacy of asthma chemotherapy. Becodisk significantly
      reduces bronchial reactivity to nonspecific mediator substances, is simple in use
      and well tolerated. It is recommended for basic therapy in various bronchial
      asthma forms managed with local corticosteroids.

PMID- 9273402
TI  - [Role of macrolides in the treatment of outpatient pneumonia].

PMID- 9273403
TI  - [Chronic obstructive bronchitis: clinical, diagnostic and therapeutic aspects].

PMID- 9273404
TI  - [Erosive lesions of gastroduodenal mucosa: etiology, pathogenesis, clinical
      features, treatment].

PMID- 9273405
TI  - [Arterial hypertension].

PMID- 9273406
TI  - [Hematuria].

PMID- 9273407
TI  - [Respiratory distress syndrome in adults with trauma or some other diseases].

PMID- 9273408
TI  - Management of coarctation with multiple calcified aneurysms of the intercostal
      arteries in adults.
AB  - Coarctation of the aorta in adult patients carries an increased but acceptable
      surgical risk. Our experience emphasizes the technical advantage of an
      alternative, simpler surgical procedure, such as bypass grafting between the
      subclavian artery and descending aorta, when one is faced with a friable aorta
      and concomitant large aneurysms of the intercostal arteries.

PMID- 9273409
TI  - [More distinct rules when taking care of the deceased. New regulations give
      better directives].

PMID- 9273410
TI  - [TDR--a functioning model for international cooperation. Four tropical diseases
      are close to eradication].

PMID- 9273411
TI  - [Who should guarantee research ethics? Voluntary scrutiny is better than the one
      prescribed by law].

PMID- 9273412
TI  - [A reply on research ethics: scientists' awareness is not a sufficient
      guarantee].

PMID- 9273413
TI  - [A letter to the chairman of the Medical Society: dangerous to have "wrong" views
      -what does the Society do?].

PMID- 9273414
TI  - [Robert Leth answers: our leadership program is the opposite of repression].

PMID- 9273415
TI  - [Differentiate between the mildly gifted and the mildly retarded].

PMID- 9273416
TI  - [What does poorly gifted mean?].

PMID- 9273417
TI  - [Strict and clear definitions are needed].

PMID- 9273419
TI  - ["Supervise" the competence of qualified physicians].

PMID- 9273418
TI  - [The role of insurance company physicians is merely consultation].

PMID- 9273420
TI  - [Health care personnel could slow down the greenhouse effect].

PMID- 9273421
TI  - [Only professionals can interpret medical data on prescriptions].

PMID- 9273422
TI  - [Allergic reactions to peanuts and soya. The life-threatening/fatal cases can be
      prevented].

PMID- 9273423
TI  - [Fatal and severe food hypersensitivity. Peanut and soya underestimated
      allergens].
AB  - Severe allergic reactions caused by foodstuffs have been reported in Sweden since
      1993, 60 cases, five of them fatal, occurring during the first 3-year period.
      More than 70 per cent of all reactions reported were caused by patients, soya
      beans, nuts or almonds. In only 13 per cent of reported cases were the patients
      over 17 years of age. Several severe reactions were caused by soy protein, and
      mainly in children and adolescents with extremely severe peanut allergy and
      asthma. In many cases, severe symptoms first appeared more than one hour after
      soy intake. The report suggests soy allergy to be associated with an
      underestimated risk of severe reactions.

PMID- 9273424
TI  - [Progress concerning vertigo and dizziness. Now most patients can receive
      symptomatic relief].

PMID- 9273425
TI  - [Minor mortality differences between hospitals of different sizes].

PMID- 9273426
TI  - [Pharmacological treatment of alcohol dependence. Acamprosate and naltrexone
      offer new approach].

PMID- 9273427
TI  - [Protein drugs can be designed now. Targeting and cancer destroying drugs soon
      available].

PMID- 9273428
TI  - [The decisive steps cost billions. Extensive studies provide answers for many
      questions].

PMID- 9273430
TI  - [Estrogen therapy and risk of thrombosis].

PMID- 9273429
TI  - [A meeting of experts on epilepsy. Aim at monotherapy. Consider early surgery].

PMID- 9273431
TI  - [Contact dermatitis caused by ketoprofen].

PMID- 9273432
TI  - [Esophageal injury in treatment with Doryx].

PMID- 9273433
TI  - [Abuse of Imovane and Stilnoct].

PMID- 9273434
TI  - [Evaluation of training quality in the field of occupational medicine.
      Methodologic principles and a perspective of assessment tool development].
AB  - Bearing in mind a growing interest in the quality of educational processes the
      authors stressed the need for addressing this issue in the field of occupational
      medicine. They discussed major principles of the internal system of quality
      assessment and the possibility of adopting two instruments for evaluating
      (controling) the quality of teaching and learning: a questionnaire for self
      assessment of acquired/transmitted competences and a test for assessing the
      progress in acquiring knowledge and skills necessary to solve problems.

PMID- 9273435
TI  - [Silicon carbide, occupational exposure, proposed MAC values].
AB  - Occupational exposure to dust silicon carbide production and exploitation of its
      products was evaluated. Individual dosimetry was used to measure concentrations
      of total and respirable dusts; concentration of respirable mineral fibres was
      measured by means of light microscopy; the distribution of fiber length was
      analysed by employing a laser FM-7400; morphology of dust molecules was analysed
      in light and electron microscopes; x-ray diffraction and infrared spectrometry
      was used to identify dust mineral composition. Concentrations of total dust at
      workposts involved in silicon carbide production ranged between 5.0 and 14.0
      mg/m3 (mean = 10.3 mg/m3); concentration of respirable fraction between 0.1 and
      1.9 mg/m3 (mean = 1.1 mg/m3); and concentration of respirable mineral fibres
      between 0.42 and 1.04 f/cm3 (mean = 0.64 f/cm3). In the plants where SiC products
      were used the mean concentrations of total dust and respirable mineral fibres
      were about two times lower, and the concentrations of respirable fraction about
      five times lower. In the workpost air the presence of carborundum, mullite and
      cristobalite was revealed. A proposed MAC value for SiC dust (nonfibrous)
      containing less than 2% of free crystalline silica accounts for 10 mg/m3 for
      total dust.

PMID- 9273436
TI  - [The influence of computer work on reaction time and accuracy in VDT operators].
AB  - The study of simple reaction to light and sound, and differential reaction was
      carried out on the group of VDT operators (n = 62) and the group of persons not
      involved in VDT operation (n = 38). Concentration ability was tested with Couve's
      test twice a day, i.e. before and after work. In the analysis of the results,
      reaction time and the accuracy of psychomotor trials measured by the number of
      errors committed were considered. None of the research models disclosed
      statistically significant differences between the average figures calculated for
      the VDT operators and the other group. The figures registered before and after
      work in each group were not significant either. Both group also failed to show
      the influence of age on the duration of reaction. The ability to concentrate was
      lower among operators than among those not involved in VDT operation, and it
      decreased after work, especially in the oldest subgroup.

PMID- 9273437
TI  - [Reliability of routine measurements of the atmospheric air pollutant nitrogen
      dioxide].
AB  - On the basis of an external quality control of nitrogen dioxide measurements in
      the atmospheric air (emmission), the preparation of control material, its
      evaluation and durability are presented. The results of the control test carried
      out in the spring 1995 is also discussed.

PMID- 9273438
TI  - [Quantitative evaluation of health risk associated with occupational inhalation
      exposure to vinyl chloride at production plants in Poland].
AB  - Vinyl chloride is classified by the IARC in group 1-human carcinogens. In Poland
      occupational exposure to vinyl chloride is found among workers employed in many
      branches of industry, among others in the industry of vinyl chloride synthesis
      and polymerization as well as in the plastics, footwear, rubber, pharmaceutical
      and metallurgical industries. Concentrations observed range from the noon
      determinable level to 90 mg/m3, at the MAC value equal to 5 mg/m3. Neoplasm of
      liver is a major carcinogenic effect of vinyl chloride. Hence, the health
      assessment focused on this critical risk. Four different linear dose-response
      models, developed by several authors and based on results of different
      epidemiological studies, were used to characterise the extent of cancer risk
      depending on the level of vinyl chloride concentrations. The estimated risk
      related to a forty-year employment under exposure equal to MAC values (5 mg/m3)
      fell within the range from 2.9.10(-4) to 2.6.10(-3). As the figures depict it did
      not exceed the acceptable level (10(-3)).

PMID- 9273439
TI  - [Changes in bioelectric function of rabbit cerebral cortex after intraperitoneal
      injection of organic solvents. I. Toluene and m-xylene].
AB  - The goal of the study was to implement the method and to use it in identifying
      the extent of neurotoxic effect of organic solvents on the basis of changes in
      spontaneous (EEG) and evoked (evoked potentials) function of cerebral cortex and
      hippocamp induced under conditions of single exposure. Electrophysiological
      experiments were performed on rabbits with electrodes chronically implanted into
      selected structures of the brain. The examinations revealed quantitative
      differences in the postinjection EEG picture of cerebral cortex and hippocamp as
      well as in morphology of potentials evoked by visual stimulus and electric
      irritation of the brain. Concentrations of solvents in peripheral blood were
      determined on rabbits nonoperated by gas chromatography linked with a head-space
      technique. Ten and thirty minutes after intraperitoneal injection of equimolar
      quantities of organic solvents higher concentration of toluene when compared to
      the of m-xylene was found in the blood of experimental animals.

PMID- 9273440
TI  - [Biomarkers of hepatotoxic effects: their usefulness in occupational medicine].
AB  - Medical screening and the resultant monitoring of health effects induced by
      hepatotoxins present in workplaces become of still greater importance in the
      assessment of occupational health and safety. Health effects of occupational and
      nonoccupational hepatotoxic factors may be acute, subacute or chronic. Laboratory
      tests (biomarkers) used in screening for detection of asymptomatic damages of the
      liver should satisfy the following three criteria: 1. they should provide
      positive or negative predictive information, namely the information about
      possible development of clinically evident hepatopathy; 2. they should be very
      sensitive and specific in order to ensure a correct identification of the
      developing disease; and 3. they should provide information which of clinical
      biomarkers should be applied subsequently in order to confirm and facilitate the
      diagnosis of hepatopathy related to exposure to occupational hepatotoxins or to
      eliminate such a relationship. It should be also remembered that for assessing
      disorders in hepatic functions those biomarkers should be selected which are most
      effective in identifying both persons with hepatopathy induced by environmental
      hepatotoxins and those who are free from the liver damages. It should be stressed
      that to date none of the existing biomarkers is sensitive and specific enough to
      assess alone all the functional systems of the liver.

PMID- 9273441
TI  - [Documentation problems for occupationally related neoplastic diseases].
AB  - The author suggests procedures which can improve the process of identifying an
      occupational background of neoplastic diseases, bearing in mind a low number of
      reported cases of occupational cancer in Poland and a concurrent lack of
      justification (on the basis of data included in a notification from) for some of
      them. Controversy over diagnosis of neoplasms induced by ionizing radiation is
      also highlighted. The improved certification of work-related neoplastic diseases
      must involve each phase of an occupational disease diagnosis: clinical diagnosis
      with complete and correct medical history, morphological confirmation of the
      diagnosis, indispensable in the case of cancer, with identification of the
      primary site of the cancer, identification of causal factor and the exposure
      size, and occupational disease notification. The author also indicated
      shortcomings of an occupational disease notification form in regard to neoplastic
      diseases and suggested its modification.

PMID- 9273442
TI  - [Lipid peroxidation as a toxic mode of action for lead and cadmium].
AB  - Recent studies have shown that lead and cadmium deplete glutathione and protein
      bound sulfhydryl groups, resulting in the production of reactive oxygen species.
      As a consequence enhanced lipid peroxidation, DNA damage and altered calcium and
      sulfhydryl homeostasis occur. Lipid peroxidation is often discussed as a cause of
      metal-induced toxicity, although many other authors suggest a pivotal role of
      interaction with sensitive SH groups in determining cadmium and lead toxicity.

PMID- 9273443
TI  - [Biomarkers in diagnosis of kidney diseases caused by chemical toxins].
AB  - As yet there has been no evidence produced that nephrotoxic chemicals damage
      nephron in sites, characteristic of a given toxin. A number of nephrotoxic
      effects result rather from changes induced by these substances mostly in the
      peripheral circulatory system than from a direct effect of chemical toxin on the
      kidneys. In many cases the morbid process in the kidneys does not emerge until a
      considerable number of nephrons is already damaged. Therefore, it is essential
      that doctors, attending patients exposed to nephrotoxins, have at their disposal,
      during periodical examinations, appropriate laboratory tests (biomarkers) able to
      detect subclinical forms of chemical damage of the kidneys. These biomarkers
      should also help to identify which of the functional parts of the kidneys have
      been damaged. It seems that determination of protein excreted with urine is one
      of the best biomarkers most frequently used to detect the dysfunction of renal
      glomerulus. It is recommended that the relationship between urine concentration
      of total protein and urine concentration of creatinine be determined. In the
      group of biomarkers of tubule dysfunction the measurement of substances usually
      reabsorbed from glomal filtrate (low-molecular protein) in proximal tubule or
      determination of enzymes' activity in urine (e.g. N-acetylo-glucosoaminidase) and
      those cellular components which are not excreted with normal urine are
      recommended. In the assessment of distal renal tubule dysfunction it is advised
      to examine urine osmolarity and/or determination of Thamm-Horsfall glycoprotein.

PMID- 9273444
TI  - [Occupational exposure of medical personnel to chemical factors affecting
      fertility].
AB  - Exposure to factors present in the working environment may exert an adverse
      effect on both those directly and on their progeny. Together with large
      populations exposed to harmful factors in different branches of industry
      (chemical, metallurgical, textile etc.), health service workers should be also
      taken into account as another significant group exposed. Factors affecting
      fertility, health service workers are mostly exposed to, are as follows:
      cytostatic drugs, chemicals used in sterilization, gases for general anaesthesia
      and enormous number of factors the health service workers are in contact with in
      laboratories. The authors reviewed the world literature and presented kinds of
      harmful factors and their effect on fertility in persons employed in health
      services and exposed to them.

PMID- 9273445
TI  - [Conference of the American Occupational Hygienists. 18-24 May 1996, Washington,
      USA].

PMID- 9273446
TI  - [Exchange of putrescine and potassium between cells and media as a factor in the
      adaptation of Escherichia coli to hyperosmotic shock].
AB  - Putrescine/potassium exchange in response to hyperosmotic stress was studied. The
      addition of 0.3 M NaCl or 0.44 M sucrose to an exponentially growing E. coli
      culture induced potassium uptake and putrescine release from the cell. Potassium
      added to an osmotically stressed potassium-deficient culture was readily absorbed
      by cells; this was accompanied by the loss of intracellular putrescine, both free
      and bound. Since DNA is the main binding site of putrescine, the loss of bound
      putrescine caused a relaxation of DNA supercoiling. The increase in the
      intracellular content of potassium not only restored but also enhanced DNA
      supercoiling as compared to the initial level. In vitro experiments showed the
      degree of plasmid DNA supercoiling to rise drastically at potassium
      concentrations of 300-500 mM, while different putrescine concentrations affected
      this parameter differently. Thus, the physiological concentrations of putrescine
      (below 1 mM) greatly augmented DNA supercoiling, whereas higher concentrations (5
      10 mM) exerted a relaxing effect. A change in DNA supercoiling in vivo in
      response to osmotic stress is the result of competition between biogenic and
      abiogenic cations for the sites of binding to polyanionic DNA structures. A
      change in DNA topology serves as the regulatory factor controlling the expression
      of genes responsible for cell adaptation to osmotic stress.

PMID- 9273447
TI  - [Genetic control of the destruction of surface-active agents].
AB  - Degradation of anionic, cationic, and zwitterionic surfactants, such as
      alkylbenzene sulfonate, ethonium, amidobetaine, and alkylaminobispropionate, by
      pseudomonads can be controlled by plasmid genes. The majority of plasmids of
      surfactant-degrading strains are capable of conjugal transfer.

PMID- 9273448
TI  - [Therapeutic use of monoclonal antibodies].
AB  - Three monoclonal antibodies (mAbs) have been approved for the treatment of
      transplant rejection, sepsis, and colorectal carcinoma. The breakthrough,
      however, has not yet been achieved, in contrast to diagnostic mAbs. The general
      applicability for a large number of patients and long-term therapeutic success
      have not yet been proven. A complete cure by mAbs alone has been observed in only
      a few cases. In many cases conventional medications have to be administered in
      parallel. There are a number of inherent problems which reside in both the
      biochemistry of the antibodies and the biology of the patients. There is no
      doubt, however, that in 5-7 years mAbs will be used routinely to treat cases of
      rejection of transplanted organs, autoimmune diseases, infections and cancer.

PMID- 9273449
TI  - [Fire-eaters, a breath-taking act?].
AB  - Burns due to fire-eating are relatively rare. In a short period (6 months) four
      patients (men aged 9, 22, 27, and 15) were sent to the Burns Centre of the
      Martini Hospital of Groningen, the Netherlands. They had used car petrol in stead
      of paraffin oil. Their burns were not very severe but they were hospitalized
      because of the risk of an inhalation injury, especially oedema of the glottis.
      Signs related to inhalation injury are: burned hairs of the nose, smut on the
      mucous membrane in the mouth and nose or in the sputum, hoarseness, increase of
      tachypnoea and dyspnoea. Burns in the face are suggestive of an inhalation
      injury, of which there are three forms: oedema of the glottis, tracheobronchitis,
      and acute respiratory distress syndrome (ARDS). The four patients did not develop
      inhalation injury and recovered completely.

PMID- 9273450
TI  - [Barrett esophagus and Barrett carcinoma].
AB  - The incidence of Barrett carcinoma has increased almost six-fold in the last 20
      years. Barrett oesophagus is defined as the presence of metaplastic columnar
      epithelium in the oesophagus in continuity with the gastric mucosa. It is
      regarded as an acquired abnormality, developed as a result of chronic (duodenal)
      gastro-oesophageal reflux. It is especially the intestinal type of columnar
      epithelium that has a greatly enhanced risk of malignant degeneration. It is
      advisable that patients with a Barrett oesophagus should regularly be examined
      endoscopically, with extensive tissue biopsy. Presence of Barrett epithelium
      without dysplasia or with only moderate dysplasia does not in itself constitute
      an indication for supplementary treatment. Major dysplasia constitutes an
      indication for prophylactic resection. In the treatment with curative intention
      of Barrett carcinoma, surgery is the therapy of first choice.

PMID- 9273451
TI  - [Women with hereditary risk of breast cancer: consensus of surgical
      representatives of study groups for hereditary tumors regarding intensive
      monitoring, diagnosis and preventive resection].
AB  - Women in whom a hereditary increased risk of breast cancer is established are
      often moved by anxiety to ask a surgeon for intensive periodical checking of the
      breasts or prophylactic resection breast tissue. This article contains a
      consensus on the relevant policy reached by surgeons from the two cancer centres
      and eight university hospitals in the Netherlands. Intensive follow-up is
      indicated only when the risk of breast cancer is twice as high as in women from
      the population in general. The age from which check-up examinations are carried
      out is from 25 years or from 5 years before the age at which the youngest
      relative developed breast cancer. For female gene carries from families with
      hereditary breast cancer, whether or not identified, the risk of death from
      breast cancer in spite of intensive follow-up is 7-20%. Preventive bilateral
      mastectomy is recommended only in case of a demonstrated gene mutation or a life
      long risk of breast cancer in excess of 50%. Even after preventive surgical
      treatment, women should report annually for examination, because frequently a
      little mammary tissue remains behind.

PMID- 9273452
TI  - [Surgical treatment of carpal tunnel syndrome: endoscopic or classical (open)? A
      prospective randomized trial].
AB  - OBJECTIVE: To compare the results of open with endoscopic release of the carpal
      tunnel in patients with the carpal tunnel syndrome. DESIGN: Randomised
      prospective study. SETTING: General hospital Zeeuws-Vlaanderen, Oostburg and
      Terneuzen, the Netherlands. METHOD: 178 patients were randomised for open or
      endoscopic release. The symptom severity score and functional status score were
      completed before and three months after the procedure. One week after the
      operation the patients' postoperative pain was measured on a 10-point visual
      analogue scale. Differences were analysed using the Chi-square test or the t
      test. RESULTS: Randomisation failed in two patients; 85 patients had an
      endoscopic release and 91 patients had an open release. The postoperative pain
      was significantly less in the endoscopic group. Improvement in symptom severity
      score and functional status score was the same in both groups. There was no
      difference in absence from work. Two local complications occurred in the
      endoscopically treated group. Of the patients 25% were not or only slightly
      satisfied with the results. CONCLUSION: Endoscopic release of the carpal tunnel
      is as effective as the open release but it gives less postoperative pain. Because
      of the risk of complications and the additional costs, the endoscopic release is
      not the preferred method for treatment of the carpal tunnel syndrome, however.

PMID- 9273454
TI  - [Thorn apple poisoning].
AB  - A 20-year-old man presented with signs of thornapple intoxication: restlessness,
      disorientation, hallucinations, euphoria, and furthermore dry and red skin and
      symmetrical dilation of the pupils. Thornapple intoxication mimics atropine
      intoxication. Thorn apples (Datura stramonium) are seemingly becoming popular as
      a hallucinogenic drug. When the symptoms are mild gastric lavage leaving active
      charcoal in the stomach afterwards will suffice. In case of severe symptoms
      treatment with physostigmine is indicated.

PMID- 9273453
TI  - [Risk factors for cardiovascular diseases in Turks in Amsterdam and in Ankara].
AB  - OBJECTIVE: To determine the prevalence of the main risk factors for
      cardiovascular disease in Turks in Amsterdam and in Ankara, and to compare the
      results obtained in these two groups with each other and also with those obtained
      in a group of indigenous Dutch residents living in the same districts. DESIGN:
      Cross-sectional observational study. SETTING: Districts 'Oost' and 'De Pijp' in
      Amsterdam, the Netherlands, 'Camlik' and 'Besikkaya' in Ankara, Turkey. METHODS:
      Plasma glucose and lipids were determined in 149 Turkish residents living in
      Amsterdam and 145 Turkish subjects in Ankara with comparable socio-economic
      status (66 and 74% of those who were asked to participate). Blood pressure was
      also measured by mercury sphygmomanometry. Questionnaires were completed on
      smoking habits, alcohol consumption, physical activity, consumption of food
      containing saturated fat, and the existence of heart and vascular disease or
      hypertension. Results were compared between groups and also with the findings
      obtained in a group of indigenous Dutch subjects living in the same districts in
      Amsterdam by the Peilstationsproject of the Rijksinstituut voor Volksgezondheid
      en Milieu (Sounding station project, National Institute for Public Health and the
      Environment). RESULTS: Turkish men in Amsterdam had higher systolic blood
      pressures, lower HDL cholesterol values and higher total cholesterol/HDL
      cholesterol ratios, and were more obese than men in Ankara and Dutch men in
      Amsterdam. Glucose concentration and total cholesterol and LDL cholesterol
      concentrations of Turkish men in Amsterdam were higher than the values of men in
      Ankara. The risk profile of Turkish women was also more unfavourable compared
      with that of women in Ankara, but the differences were less than in the men. They
      had lower HDL cholesterol values, higher LDL cholesterol and glucose and smoked
      more often than women in Ankara. Turkish women in Amsterdam also had higher
      systolic and diastolic blood pressures and were more obese than Dutch women in
      Amsterdam. CONCLUSION: Turkish residents in Amsterdam have more risk factors for
      cardiovascular disease than their countrymen living in Ankara, and also compared
      with indigenous Dutch citizens living in the same districts. Their risk factor
      profile, therefore, is not intermediary between that of Turkish subjects in
      Ankara and the indigenous Dutch citizens, as might be expected in view of the
      mortality figures.

PMID- 9273456
TI  - [Euthanasia and other medical decisions involving life's end, 1990-1995].

PMID- 9273455
TI  - [Not more symptoms with mefloquine use than with other drugs in malaria
      prophylaxis].

PMID- 9273457
TI  - [Tethered spinal cord syndrome in adults].
AB  - The tethered spinal cord syndrome is more often encountered in children, but does
      also occur in adults. Its clinical spectrum comprises low back pain, neurological
      deficits such as distal motor weakness and trophic and sensory disturbances in
      the legs, urological symptoms and such musculoskeletal signs as scoliosis or foot
      deformities. In addition, cutaneous lesions or subcutaneous lipomas in the
      lumbosacral region may be indirect signs of an intraspinal pathology. This
      consists in a tight, thickened and sometimes shortened filum terminale, an
      intraspinal lipoma, intradural scar formation or other lesions that lead to conus
      fixation. The common mechanism of injury of these types of pathologies is an
      impairment of longitudinal movement of the spinal cord, especially the conus
      medullaris, which subsequently leads to chronic local ischemia. Diagnosis is most
      readily achieved by magnetic resonance imaging. Treatment is aimed at the
      restoration of cord mobility by means of microsurgical release of the conus, the
      cauda equina and the filum terminale with the aid of cauda equina
      neuromonitoring. Further progression can be effectively halted; in fact almost
      half of the patient actually improve. Therefore, every patients presenting with
      the clinical diagnosis of tethered cord syndrome should be offered specialized
      surgical treatment.

PMID- 9273458
TI  - [Infection: impaired consciousness as the initial symptom. Clinical and
      pathophysiologic aspects of septic encephalopathy].
AB  - Septic encephalopathy (SE) is present in up to 70% of all patients with sepsis.
      In some cases, SE may proceed other parameters of sepsis. Loss of consciousness
      to a various extent is the leading symptom. CSF findings and CCT are usually
      unremarkable. EEG is a sensitive parameter to monitor SE. EEG-changes deteriorate
      in correspondence to the degree of SE. If sepsis can be treated successfully,
      clinical and electrophysiological signs are completely reversible. SE has a
      complex etiology. Bacterial endotoxins and other microbial products trigger the
      release of a multitude of mediators of sepsis. Due to liver dysfunction in
      sepsis, the brain neurotransmitter profile may be deranged. Other etiological
      factors include bacteriemia, liver or renal dysfunction, fluid and electrolyte
      imbalance, hypoglycemia and drug effects. Due to the prognostic significance of
      early adequate treatment, recognition of SE as a possible initial sign may be
      crucial for patients with sepsis.

PMID- 9273459
TI  - [New developments in diagnosis and therapy of primary non-Hodgkin's lymphoma of
      the central nervous system].
AB  - Primary central nervous system lymphomas (PCNSLs) are increasing in frequency
      both in immunocompetent and immunodeficient individuals. The majority of PCNSLs
      are high grade B cell lymphomas. In AIDS patients most tumors contain EBV genome.
      PCNSLs usually present as intracerebral, often deep-seated lesions half of which
      are multilocular. Less frequent are diffuse periventricular, exclusively
      leptomeningeal, ocular or spinal spread. On imaging PCNSLs show as contrast
      enhancing lesions with relatively little perifocal edema. CSF protein is usually
      elevated. Malignant cells are present in 20-30% of cases. Demonstration of a
      monoclonal B cell population by immunocytology or FACS analysis may also be
      diagnostic. Once PCNSL is suspected extensive systemic evaluation is not useful.
      Instead, (stereotactic) biopsy of brain lesion(s) should be performed. Prior to
      biopsy, corticosteroids should be withheld as they may obscure diagnosis.
      Symptomatic edema or increased intracranial pressure should therefore initially
      be treated with osmotherapeutics. All immunodeficient patients should receive
      empiric anti-toxoplasmosis therapy for about 14 days prior to biopsy. AIDS
      patients with PCNSL survive 3 to 5 months (median) after whole brain irradiation
      and usually do not benefit from chemotherapy. Immunocompetent patients have a
      median survival of 12 to 18 months after whole brain irradiation alone, but a
      median survival of 33 to 43 months after combined radiochemotherapy using
      cytostatic drugs which penetrate the blood-brain barrier. Based on these
      encouraging results current concepts aim to intensify chemotherapy and to reduce
      or delay radiotherapy in the treatment of immunocompetent patients.

PMID- 9273460
TI  - [Expanded illness spectrum of human spongiform encephalopathies or prion
      diseases].
AB  - Since its first description by H.G. Creutzfeldt and A. Jakob, six forms of human
      spongiform encephalopathies have been described. Besides Creutzfeldt-Jakob
      disease (CJD), a new variant CJD (nvCJD), Gerstmann-Straussler-Scheinker syndrome
      (GSS), fatal familial insomnia (FFI) and potentially familial progressive
      subcortical gliosis have been reported. The most likely causative agent of these
      and at least six animal-transmissible spongiform encephalopathies (TSE) is a
      structurally altered form of a regular cellular protein, designated prion. The
      best known animal forms are bovine spongiform encephalopathy (BSE) and scrapie.
      The clinical spectrum of human spongiform encephalopathies has been expanded in
      recent years by the discovery of new, partially genetically determined forms. The
      currently available clinical, neurophysiological, neuroradiological, biochemical
      and molecular-biological methods permit only a probable diagnosis of CJD. A
      definite diagnosis can only be achieved by the neuropathological demonstration of
      the pathological prion protein (PrPSc). The transmission of BSE to humans has
      neither been shown nor definitely excluded.

PMID- 9273461
TI  - [Follow-up and prognosis of early summer meningoencephalitis].
AB  - Sixty-three patients with tick-borne encephalitis were studied for sequelae up to
      5 years after the acute illness (median: 12 months, range: 1-44 months). Patients
      were examined clinically, by neuropsychological testing and by
      electroencephalography. The clinical presentation during the acute stage was as
      follows: Meningitis (M,n = 12), Meningoencephalitis (Me,n = 27),
      Meningoencephalomyelitis (My,n = 15), and Meningoencephaloradiculitis (R,n = 9).
      A total of 59 patients reported a neurasthenic syndrome after discharge, which
      correlated with the severity of the acute illness. Twenty patients were not able
      to work because of reduced stress tolerance, fatigue or an elevated emotional
      sensitivity, which lasted for 3 months at most. In some patients hypacusis (n =
      7), severe dysarthria and dysphagia (n = 4) remained essentially unimproved for
      years following the acute illness. While in 8/9 patients with radiculitis paresis
      of the extremities improved well over months to years, improvement was quite
      limited in all patients with myelitis. In 41/55 patients, investigations by
      electroencephalography revealed normal findings even within months after acute
      illness. Persistent cognitive deficits were present only in 7/11 patients with a
      severe course of disease.

PMID- 9273462
TI  - [Frequent problems with antibiotic chemotherapy of bacterial CNS diseases. Case
      reports and recommendations for initial treatment].
AB  - The initial antibiotic treatment of bacterial meningoencephalitis has major
      implications for the course of the disease. The current spectrum of infectious
      agents must be considered. Antibiotics have to reach sufficient concentrations in
      the blood and cerebrospinal fluid for a bactericidal action to occur at the site
      of infection. Frequent problems arising in this condition are: (1) the non
      observation of listerial infections, (2) the use of antibiotics not sufficiently
      active against gram-positive bacteria in pneumococcal meningitis, (3) the
      development of meningitis following the use of ciprofloxacin in respiratory tract
      infections, (4) the hasty change in antibiotic regimens in focal parenchymal
      infections during delayed response to therapy, (5) the use of bacteriostatic
      antibiotics, and (6) the delay in administering sufficient antibiotic therapy
      during fulminate meningococcal meningitis. Problems arising from these conditions
      are illustrated by case reports.

PMID- 9273463
TI  - [Myasthenic crisis caused by azathioprine-induced fever].
AB  - Azathioprine is an established immunosuppressive agent in the treatment of
      myasthenia gravis. In rare cases, complications such as hypersensitivity
      reactions including fever may occur. A 73-year-old patient with the first
      manifestation of myasthenia gravis was immunosuppressed with azathioprine and
      prednisolone in addition to pyridostigmine treatment and discharged from hospital
      without symptoms. Ten days after onset of azathioprine therapy, he developed
      fever and a myasthenic crisis requiring artificial ventilation. Azathioprine was
      discontinued. Microbiological and radiological examinations revealed no signs of
      infection. After clinical improvement azathioprine was re-started, and following
      a single dose the patient again presented with fever and tachycardia.
      Azathioprine was discontinued, and all symptoms abated within a day. These
      symptoms were most probably caused by an azathioprine-induced hypersensitivity
      reaction. Life-threatening myasthenic crises may occur if such a hypersensitivity
      reaction remains unrecognized in patients with myasthenia gravis.

PMID- 9273464
TI  - [Vasculitis course of neuroborreliosis with thalamic infarct].
AB  - A-20-year-old man without vascular risk factors presented with paraesthesia of
      the left side of the body with acute onset. Cerebral magnetic resonance imaging
      showed an infarction in the right thalamus. Intra-arterial digital subtraction
      angiography revealed stenosis of the right thalamic vessels. Recent infection by
      Borrelia burgdorferi was demonstrated by typical findings in the cerebrospinal
      fluid: lymphocytic pleocytosis and intrathecal synthesis of borrelial-specific
      antibodies. The diagnosis of a borrelial-induced vasculitis with secondary
      thalamic infarction was made from these findings. After antibiotic treatment with
      cefrtriaxone, the patient was discharged without residual complaints.

PMID- 9273465
TI  - [Neurologic and psychiatric symptoms of legionella infection. Case report and
      overview of the clinical spectrum].
AB  - Legionella is a frequent etiologic agent in the development of both nosocomial
      and community acquired pneumonias. Involvement of the nervous system is common in
      Legionella infections. We present a case of Legionnaires' disease which
      illustrates distinctive neurologic findings including delirium and cerebellar
      dysfunction. Furthermore, this paper reviews the neurological and psychiatric
      features of 609 Legionella infected patients with involvement of the nervous
      system. The most common signs were disorientation (58%), headache (52.4%), and
      somnolence (39.7%). Less frequent or rare were: cerebellar dysfunction (11.2%),
      hallucinations (8.4%), agitation or stupor (4.1%), affective disorders (3.1%),
      peripheral neuropathy (2.8%), pyramidal disturbances (2.1%), memory loss (1.6%),
      seizures (1.5%), cranial nerve palsies (1.5%), incontinence (0.7%), and
      extrapyramidal disturbances (0.3%). Cranial CT scans, cerebrospinal fluid
      findings, and nerve and muscle biopsies were usually unremarkable.
      Neuropathologic examinations failed to demonstrate specific characteristics.
      Hyponatremia and serum CPK level elevation were present in up to 89% and 50% of
      patients, respectively. Prognosis of disturbances of the nervous system was
      mainly good. We conclude that in the presence of definite neurological findings,
      pulmonary infection, hyponatremia, and CPK elevation Legionella infection should
      be considered.

PMID- 9273466
TI  - [Neurogenic temporomandibular joint dislocation. Definition and therapy with
      botulinum toxin].
AB  - Dislocation of the temporomandibular joint results from trauma, articulation
      disorders and changes in the equilibrium of the masticatory muscles. Previous
      classifications were mostly oriented on the interrelationships between the
      anatomical positions of the dislocated articular surfaces, like luxation,
      subluxation and discuss luxation. Etiologically, a distinction is made between
      traumatic and non-traumatic dislocation. Dislocation of the temporomandibular
      joint is described as a complication of a number of neurological diseases. We
      report on a patient who suffered recurrent dislocations of the temporomandibular
      joint as a complication of multiple sclerosis and whose luxations were
      successfully treated with botulinum toxin, thus warranting the introduction of
      the term "neurogenic dislocation of the temporomandibular joint".

PMID- 9273467
TI  - [Recommendations of Bavarian Muscle Centers of the German Neuromuscular Disease
      Society for home ventilation of neuromuscular diseases of adult patients].
AB  - During recent years home ventilation has been shown to be useful for a growing
      number of patients with neuromuscular diseases and respiratory insufficiency
      caused by weakness of the respiratory muscles. Despite its technical simplicity,
      home ventilation leads to a number of social, ethical, medical and
      infrastructural problems. This consensus paper discusses the special situation of
      patients with neuromuscular diseases in home ventilation and describes the
      current thinking in the following topics: (1) definition of home ventilation; (2)
      aims of home ventilation; (3) indications and preconditions of home ventilation;
      (4) techniques and forms of home ventilatory support; (5) preparation for and
      practical questions of home ventilation; (6) stopping home ventilation.

PMID- 9273468
TI  - [Type I Charcot-Marie-Tooth syndrome. Disability and management].
AB  - Molecular genetic research on Charcot-Marie-Tooth 1 syndrome (CMT 1) progresses
      rapidly, still obviously no cure is available for affected individuals. Our aim
      was to investigate current management in clinical CMT 1 50 patients with Charcot
      Marie-Tooth syndrome type I (CMT 1) were explored for applied means of therapy
      and use of health care institutions. We documented the number of annual
      appointments at a neurologist, orthopaedist and psychologist. Previous admissions
      to hospitals and rehabilitation centres and surgical procedures were assessed.
      Practice of physiotherapy, occupational and physical therapy were investigated,
      also administered orthopaedic devices, mechanical devices and technical
      modification of car and home. Drugs prescribed were listed and the number of
      patients seeking advice at para-medical institutions was determined. Degree of
      medical support did not correlate with severity of disease. We observed that
      persons with marked disability did not uniformly receive adequate therapy. This
      was partly due to the responsible physicians, and partly due to lacking
      cooperation of the patients. Support of affected individuals and counselling to
      our opinion are to be improved. This would require further evaluation of
      therapies, establishment and distribution of guidelines, as well as motivation of
      patients, which might be facilitated by the offer of molecular genetic
      diagnostics.

PMID- 9273469
TI  - [Hypertension and peripheral arterial hemodynamics].
AB  - Sixty uncomplicated hypertensive patients (40 stable and 20 borderline) were
      studied, by strain gauge plethysmography, in comparison with 25 normotensive
      subjects, in order to evaluate the arterial hemodynamics of the lower limbs in
      essential hypertension and to verify the different pattern in borderline and in
      stable hypertensives. Resting blood flow, even if lightly decreased in
      hypertensive groups, didn't show significant differences in its mean values; Peak
      Flow, instead, was reduced proportionally to the severity of hypertension in all
      the hypertensive patients, but only in the stable hypertensives did it prove
      statistically significant. Minimal Vascular Resistances showed a similar
      behaviour; they were significantly increased only in the stable hypertensives,
      whereas Basal Vascular Resistances, were raised in all hypertensive patients, in
      the borderline group too. Finally, half time and total hyperemic time, which
      indicate vascular reactivity, were significantly decreased in all hypertensives.
      These results suggest that the stable hypertensive patients principally develop
      arterial structural changes, while the borderline hypertensive patients have only
      functional modifications, such as a reduced compliance and a hyperdynamic
      condition.

PMID- 9273471
TI  - [Traumatic lesion of the subclavian and axillary arteries].
AB  - This study comprises 11 patients with traumatic vascular injuries of the
      subclavian and axillary vessels treated in the last 13 years at the Institute of
      General and Cardiovascular Surgery of Milan. Nine patients were male and two were
      female. In two patients the cause of injury was a penetrating trauma; blunt
      trauma occurred in nine patients. The majority of injuries were caused by motor
      vehicle accidents. Two patients suffered complete brachial plexus palsies with
      complete transection of the median nerve. Seven patients were affected by
      multiple bone injuries, while major venous injury was present in one case.
      Diagnosis was established by angiography performed in all stable patients.
      Vascular repair was performed in 10 patients; 4 patients were treated by primary
      repair, and 6 patients by interposition grafts. In one case we performed a
      transluminal percutaneous angioplasty (PTA) during angiographic examination, with
      a good result. There were no postoperative vascular complications and no patient
      died.

PMID- 9273470
TI  - [Prevalence of venous diseases. The San Valentino screening and prevalence
      study].
AB  - The PAP/PEA (Prevalence of Early Atherosclerosis) study aims to define the
      prevalence of subclinical atherosclerosis in a typical population of central
      Italy. A concomitant study evaluates the prevalence of venous diseases. The first
      group of 850 patients evaluated, indicated the prevalence of superficial ve-nous
      disease, the prevalence of deep venous thrombosis and pulmonary embolism and the
      prevalence of the most common venous malformations. Also the costs of venous
      problems was considered. In conclusion some 12% of the evaluated population
      sample (male population 46%) had or had been affected in the past by a venous
      problem and 50% of them had been under some form of treatment.

PMID- 9273472
TI  - [Raynaud's phenomenon: effects of terazosin].
AB  - After considering the clinical and physiopathological aspects of Raynaud's
      phenomenon, the authors have evaluated the medium effects of therazosine in 2
      groups of patients, respectively with idiopathic and secondary Raynaud's
      phenomenon. The results show that the therazosin determines a decrease of number,
      intensity and duration of vasospastic attacks to the hands as well as an
      improvement of telethermographic and ultrasonographic findings.

PMID- 9273473
TI  - [Polydistrectual atherosclerosis in the elderly. Ischemic cardiopathy and
      obliterative peripheral arteriopathy of the lower limbs].
AB  - BACKGROUND: Numerous epidemiological studies have recently drawn attention to the
      polydistrict nature of atherosclerotic disease. In particular, it has been made
      clear the frequent association between coronary heart disease and peripheral
      arterial disease of the lower limbs. We have therefore evaluated the frequency of
      peripheral arterial disease in a consecutive unselected series of patients
      affected by coronary heart disease, over 65 and under 65. We have besides
      evaluated the frequency of some factors of risk for atherosclerotic disease on
      the subjects affected by coronary heart disease alone and in those with
      associated peripheral arterial disease. METHODS: We have studied 502 patients
      (280 males and 222 females) with coronary heart disease admitted to the II
      Division of General Medicine of Pugliese-Ciaccio Hospital of Catanzaro. Of the
      502 patients examined, 367 (72.7%) over 65 and 137 (27.3%) under 65. Factors of
      risk considered were familiarity, cigarette smoking, diabetes mellitus,
      dyslipidosis, arterial hypertension. RESULTS AND CONCLUSIONS: Peripheral arterial
      disease was present in 37% of the subjects examined. In the elderly group there
      was a frequency of 87.6%, while in subjects under 65 the frequency was 12.4%.
      Symptoms of claudicatio were present in 100% of the subjects under 65 and 58.6%
      of the elderly subjects. Risk factors that apply with greater frequency were
      diabetes mellitus, arterial hypertension and smoking. The results of our study
      show the importance of searching for stenosis even if asymptomatic in patients
      with coronary heart disease, above all if elderly.

PMID- 9273474
TI  - [The ocular fundus in ischemic cardiopathy].
AB  - BACKGROUND: This work aims to correlate retina vessel alteration with the
      possible presence of coronary alteration in the same patient. METHODS: For this
      purpose 103 patients have been studied. Of these, 63 had symptoms of coronary
      heart disease while the remaining 40 were used as a control. 29 patients, out of
      the 63, were also afflicted with angine while 34 had previously had myocardial
      infarction. Eye fundus tests and coronarography have been carried out, and risk
      factors such as high cholesterol, high blood pressure, diabetes and smoking have
      been investigated. RESULTS AND CONCLUSIONS: This work shows that there is a close
      correlation between a positive eye fundus and coronarography alteration whereas a
      negative one is not incompatible with organic lesions. A positive eye fundus due
      to alteration of retina microcirculation can be indicative of atherosclerosis in
      symptomatic patients.

PMID- 9273475
TI  - [Cellular viability and immune response in homologous cryopreserved cardiac
      valves].
AB  - BACKGROUND: Long-term durability of homograft valves is related to cellular
      viability and immunological compatibility. In this paper, we carry out a critical
      update of the relationship between cellular viability and immunology of
      cryopreserved homograft valves. BIOLOGICAL ISSUE: In the first section, we review
      the theoretical background of the superior durability of cryopreserved valves
      with high cellular viability, with respect to the "fresh" antibiotic-stored
      valves, with lower viability rates. Afterwards, a brief review of the principal
      factors influencing the homograft valve viability rate during harvesting,
      preparation, sterilization and cryopreservation phases, is performed. CELLULAR
      VIABILITY: In the second paragraph, we analyze the problem of cellular viability
      in cryopreserved valves, both for matrix cells--fibroblast--and for endothelium.
      In particular, we report the current methods of quantifications of viability and
      more recent biological researches. Correlations between biological and clinical
      data are also discussed. IMMUNOLOGICAL ISSUE: Finally, the immunological issue
      and its relationships with cellular viability is analyzed, with particular regard
      to experimental evidence and clinical implications. Moreover, we have described
      the recent hypothesis on the influence of cryopreservation on the antigenicity of
      tissues, and the laboratory researches on the long-term antibody response in
      humans after homograft valve implantation.

PMID- 9273476
TI  - [Pseudoaneurysm and aneurysm of the left ventricle. Discription of a case and
      long-term follow-up].
AB  - Left ventricle pseudoaneurysm is an uncommon complication of myocardial
      infarction; urgent operation is usually recommended, because of the high rate of
      severe complications. We report a single case with coexistence of a true aneurysm
      and a pseudoaneurysm, asymptomatic after three years of follow up in the absence
      of surgery. CASE REPORT: The patient, female, aged 69, was observed after an
      event of prolonged chest pain; ECG showed inferolateral necrosis.
      Echocardiographic examination showed: left ventricle enlargement with postero
      lateral akinesis and septo-apical aneurysm, thin apical thrombosis and mild
      mitral regurgitation; a non-contractile concameration, aside of lateral wall,
      containing some thrombotic material and communicating with the left ventricle
      through a little hole (gap of echoes), crossed by a very little inflow jet. The
      diagnosis of coexisting septo-apical "true" aneurysm and postero-lateral
      pseudoaneurysm was confirmed with CT scan, NMR and left ventriculography.
      Coronary angiography showed total occlusion of LAD and a critical stenosis of mid
      LAD. The patient refused the operation. In 36 months follow-up no symptoms nor
      significant echocardiographic changes were observed. DISCUSSION: The
      pseudoaneurysm is caused by slow fissuration of the myocardium (after a
      myocardial infarction) with adhesion of pericardium and fibrosis, resulting in a
      saccular cavity, communicating with the left ventricle by a little hole; on the
      contrary the more frequent "true" aneurysm is a progressive dilatation and
      thinning of the ventricular wall, with parietal fibrotic degeneration.
      Echocardiography may be useful in differential diagnosis, but an excellent
      quality of the images is required and false negatives and positives are frequent.
      In this case the echocardiographic features include the thickness of the
      pseudoaneurysmal wall, the very low flow through the communication hole and the
      minimal mitralic involvement. CONCLUSION: This particular pattern, when
      accurately assessed, could probably be predictive of low risk and favorable
      prognosis in patients with pseudoaneurysm.

PMID- 9273477
TI  - [Pseudoaneurysm of the left ventricle after mitral valve replacement. Diagnosis 6
      years after the intervention].
AB  - We present a case of left ventricular pseudoaneurysm diagnosed by chance 6 years
      after a second surgical intervention on the mitral valve (replacement with a St.
      Jude prosthesis). A combination of cross sectional and color-Doppler studies led
      to the correct diagnosis. A transesophageal echocardiographic investigation did
      not provide further information, while the diagnosis was confirmed by computed
      tomography with contrast agent. A retrospective analysis of previous examinations
      revealed that the pseudoaneurysm developed shortly after the mitral valve
      replacement, remaining stable over the years. The patient was clinically
      asymptomatic, the size of the pseudoaneurysm did not increase during a 2 years
      followup, and we decided to follow a conservative treatment.

PMID- 9273478
TI  - [One hundred-fifty years of general anesthesia (1846-1996)].

PMID- 9273479
TI  - [Inhaled nitrous oxide (NO) for the treatment of ARDS].
AB  - OBJECTIVE: To investigate the initial longterm effect of inhaled NO on hypoxemia
      in ARDS patients. DESIGN: Retrospective study. PATIENTS: Nine hypoxemic patients
      with ARDS (Murray Lung Injury Score, LIS, 2.8 +/- 0.3), treated with conventional
      mechanical ventilation. INTERVENTIONS: Continuous NO inhalation was started after
      a test of inhaled NO efficacy on gas exchange and hemodynamics. Long term effects
      of inhaled NO were evaluated daily in terms of arterial oxygenation and
      methemoglobin formation. RESULTS: The initial NO inhalation increased the
      PaO2/FiO2 from 141 +/- 64 mmHg to 216 +/- 70 mmHg (p < 0.0001) and decreased the
      mean pulmonary pressure from 38 +/- 7 mmHg to 32 +/- 5 mmHg (p < 0.01), the
      pulmonary venous admixture from 29 +/- 10% to 20 +/- 8% (p < 0.01) and the
      pulmonary vascular resistance from 325 +/- 97 dyne.s.cm-5 to 238 +/- 48 dyne.s.cm
      5 (p < 0.01). Daily withdrawal of inhaled NO, which was administered for 14 +/-
      16 days at 8 +/- 2 ppm, was associated with a decrease in PaO2/FiO2 by 61 +/- 32
      mmHg (p < 0.0001). During prolonged NO inhalation the FiO2 was decreased, on
      average, by 0.34 +/- 0.19 (p < 0.01), the positive end-expiratory pressure by 4
      +/- 2 cmH2O (p < 0.01) and the peak inspiratory pressure by 7 +/- 4 cmH2O (p <
      0.01). Three patients died during the ICU stay. CONCLUSIONS: Our results confirm
      the interest for inhaled NO as an additional approach for the treatment of
      hypoxemia in ARDS. Inhaled NO seems to allow for a better control of gas
      exchange, rather than for a rapid reduction of the ventilatory support.

PMID- 9273480
TI  - [Evaluation of cerebral perfusion during aortic clamping and cross-clamping in
      patients undergoing resection for abdominal aortic aneurysm. A study with
      transcranial doppler].
AB  - OBJECTIVE: To evaluate the cerebral blood flow parameters assessed by
      transcranial Doppler during aortic cross-clamping and unclamping in patients
      undergoing abdominal aortic aneurysmectomy. METHODS: Invasive intraoperative
      monitoring of mean arterial pressure (MAP) and PaCO2, and right middle cerebral
      artery (RMCA) monitoring of blood flow parameters (mean velocity "Vm" and
      pulsatility index "PI") by transcranial Doppler were performed as well as
      evaluation of the four parameters during these subsequent periods: pre-cross
      clamping, pre-unclamping, unclamping and 1-5-10-20 minutes after abdominal aortic
      unclamping. RESULTS: No significative changes of MAP, PaCO2, Vm and PI were
      noticed during the aortic cross-clamping period (77.5 +/- 18.5 SD minutes).
      During aortic unclamping Vm and MAP decreased (64 +/- 20 vs 52 +/- 20 cm/sec, p <
      0.05, and 101 +/- 8 vs 80 +/- 15 mmHg, p < 0.01, respectively). At the 1th post
      unclamping minute there was an increase from pre-unclamping values of Vm (75 +/-
      20 cm/sec, p < 0.05) and PaCO2 (42 +/- 1.5 vs 36 +/- 2 mmHg, p < 0.05), with
      persistent reduction of MAP (92 +/- mmHg, p < 0.05), even more evident at the 5th
      post-unclamping minute (Vm = 93 +/- 25 cm/sec; PaCO2 = 46 +/- 1.2 mmHg, p <
      0.001, and MAP returned to pre-unclamping value), in which there was also a
      decrease of PI (0.65 +/- 0.16 vs 0.78 +/- 0.2, p < 0.05). At the 10th minute Vm
      (83 +/- 24 cm/sec, p < 0.02) and PaCO2 (41 +/- 1.5 mmHg, p < 0.05) increments
      were present together with persistent reduction of PI (0.69 +/- 0.17, p < 0.05),
      while at the 20th post-unclamping minute also Vm, PaCO2 and PI returned to their
      pre-unclamping values. CONCLUSIONS: The Vm decrease at aortic unclamping might
      correlate with the acute changes in MAP (blood steal hypovolemia) and is likely
      due to an inadequate cerebral autoregulatory response to abrupt MAP changes. The
      arterial CO2 increase after aortic unclamping could lead to a dilation of
      cerebral arterioles and a rise of CBF (increase of Vm and decrease of PI).
      Transcranial Doppler is a simple and reliable technique for the monitoring of
      cerebral blood flow parameters and seems to be quite suitable for the recognition
      and the quantification of changes in these parameters induced by surgical
      manoeuvres able to produce hemodynamic instability.

PMID- 9273481
TI  - [Subcutaneous emphysema and pneumothorax during laparoscopic cholecystectomy.
      Description of a clinical case].
AB  - In laparoscopic surgery CO2 is insuffled under positive pressure in the
      peritoneum; this step has anesthesiological implications because of potential
      complications. A case of subcutaneous emphysema and pneumothorax occurred in a
      patient who underwent laparoscopic cholecystectomy and whose history was
      meaningless for lung pathologies is reported. The role of CO2, of the pressure in
      the abdominal cavity, of N2O and other possible causes of this complication are
      discussed. The authors emphasize the importance and the need of continuous
      monitoring to reduce perioperative morbidity and to avoid major complications in
      the course of laparoscopic cholecystectomy.

PMID- 9273483
TI  - [IRC (Italian Resuscitation Council). Recommendations for training in basic life
      support (BLS)].
AB  - This report, drawn up by the BLS Committee of the IRC, gives the guidelines for
      BLS training, according to the conclusions of the Consensus Conference (CPCR
      Methodology Consensus Meeting: BLS and training) held in Monte Conero, Sirolo
      (Ancona) on June 24th, 1994. American Heart Association and European
      Resuscitation Council guidelines, published in 1992, were considered for
      reference. This document aims to achieve two purposes: to promote standardization
      in teaching and performing BLS techniques and to outline the minimum features of
      an effective BLS program.

PMID- 9273482
TI  - [Acute iatrogenic myopathy during treatment of status asthmaticus. Our experience
      and review of the literature].
AB  - CASE REPORT: A young man was admitted to the ICU for acute asthmatic respiratory
      failure. He was sedated with propofol, curarized with pancuronium and put on
      mechanical ventilation for 15 day because of the persistent asthmatics crisis.
      Drug therapy for asthma included high-dose corticosteroids. When sedation and
      paralysis were stopped, the patient, that was fully conscious, showed flaccid
      quadriplegia. A muscular biopsy showed elective loss of the myosin thick
      filaments. Electrophysiologic evaluation was compatible with both neurologic or
      muscular pathology. The evolution of the disease was good; a drop-out performed 5
      months later showed a complete motor recovery. DISCUSSION: This case report
      confirms that in some patients, intensive treatment of status asthmaticus may
      cause myopathy. Only recently this myopathy has been correlated to an interaction
      between steroids and neuromuscular blockers. Many experimental and clinical
      observations suggest a negative interaction between steroids and non-depolarizing
      curare derivatives. In the case reported here, diagnosis was based on
      electrophysiologic examination and above all on muscular biopsy. CONCLUSION: The
      occurrence of an acute toxic myopathy should always be taken into account,
      considering the high number of patients admitted with respiratory failure
      requiring steroid treatment and curare administrative for mechanical ventilation.
      It therefore seems reasonable to reduce steroid therapy as soon as possible with
      a periodic suspension of curare administration. Curare usage should be critically
      evaluated. Some basic examination such as serum CPK monitoring should allow early
      detection of muscular damage.

PMID- 9273484
TI  - [Ultrasound-guided fine-needle aspiration biopsy of focal liver lesions].
AB  - The ultrasound guided percutaneous fine needle biopsy (US-FNAB) of focal lesions
      in the liver is indispensable in many clinical situations. During the last 12
      years, 657 US-FNAB were performed on patients with suspected neoplastic
      involvement of the liver with 22-gauge Chiba needles at our department. US-FNAB
      was performed mostly with the "free hand" technique. Sufficient material for
      cytologic analysis was obtained in 84% of the cases. The biopsies confirmed
      malignancy in 39.3%, including 9% primary hepatocellular carcinoma, 8% of the
      cases were suspect for malignancy, and in 36.7% were diagnosed benign lesion. 233
      cases were confirmed histologically and with other follow up methods. The
      sensitivity rate was 91%, and specificity was 100%. There was no false positive
      diagnosis and no noteworthy complications were observed. US-FNAB is a highly
      reliable, safe, inexpensive and easy diagnostic procedure. On the basis of our
      experience, we recommend US-FNAB as a routine, first level procedure for the
      diagnosis of focal liver diseases.

PMID- 9273485
TI  - [Experience with benazepril, a long-acting ACE inhibitor, in the management of
      diabetic hypertension].
AB  - The therapeutic advantage of the long acting ACE-inhibitor benazepril in a 12
      weeks intervention period on 23 diabetic (3 IDDM, 20 NIDDM) patients with
      essential hypertension was studied. Participants-giving informed consent before
      beginning the study-on the base of repeated casual blood pressure measurements
      were divided into "slightly" (n = 8) and "moderately" (n = 15) hypertonic groups.
      Type of diabetes, time elapsed since its manifestation, actual antidiabetic
      therapy, period of existence of the hypertension (newly discovered vs known and
      treated for a time) were independent from the point of view of entering the
      study. Initial dose of benazepril was 5-10 mg/day depending on the blood pressure
      level, followed by a stepwise dose elevation according to the control
      investigations (at weeks 2, 4, 8 and 12 casual blood pressure control, at weeks 4
      and 12 ambulantory blood pressure monitoring, ABPM as well) to a maximal daily
      dose of 20 mg. In the majority of patients benazepril was given in a morning
      single dose, in some cases because of a better tolerability divided into two
      parts. 20 patients received benazepril in monotherapy, 3 patients combined with
      other antihypertensive preparations. Parameters indicating severity of
      hypertension-hypertonic time index, hyperbaric impact-showed significant
      improvement already at week 4 when analysed in the total of patients and the
      moderately hypertonic group respectively. As a tendence the same was observed
      also in the slightly hypertonic group. No remarkable side effects, or alterations
      of the metabolic state and in the investigated laboratory parameters appeared.
      Based on these results benazepril is an effective choice in the treatment of
      diabetic hypertensive patients.

PMID- 9273486
TI  - [Hand-arm vibration syndrome in caisson miners].
AB  - Authors examined 43 caisson-miners with symptoms of the upper extremities because
      of suspicion of hand-arm vibration syndrome. Also vibration measurements were
      performed on the pneumatic hammer used by the workers. The acceleration of the
      vibration exceeded 2.5-3.5 times the maximum allowable level according to the ISO
      5349. Symptoms and signs of hand-arm vibration syndrome were found in 39 cases
      (90.7%). The vascular, peripheral neurological and locomotor system of the upper
      extremities were affected in similar frequency: 54.8; 51.6 and 51.2%,
      respectively. The most common angiological alteration was the Raynaud's
      phenomenon. Neurologically predominated the tunnel syndromes. Among the
      osteoarticular lesions the degenerative phenomena were the most frequent. In most
      cases more than one pathological alteration occurred. Fatigue fracture of the
      spinous process of vertebra D. I. appeared in one single case, degenerative
      changes of cervical spine in 34 patients (79.1%). The very common occurrence of
      the locomotor alterations and tunnel syndromes respectively can be explained
      probably also by the high physical stress required by this profession. The
      detailed examination of the locomotor system is very important by the periodical
      screening of the caisson-miners.

PMID- 9273487
TI  - [Genetic diagnosis of Williams syndrome].
AB  - Williams syndrome is a complex developmental disorder. The major cardiovascular
      component of Williams syndrome is supravalvular aortic stenosis, a progressive
      disease that may need surgical repair. Williams syndrome is associated with
      heterozygous microdeletion in the chromosomal region 7q11.23 encompassing the
      elastin gene. We have identified a new, highly informative tetranucleotide repeat
      polymorphism within the human elastin gene. This marker together with other,
      previously described elastin gene markers was used to show deletion of the
      elastin gene in nine sporadic Williams syndrome patients from Hungary.
      Application of polymorphisms within and flanking the elastin gene on chromosome 7
      provides a fast, polymerase chain reaction based method for mutational analysis
      of Williams syndrome patients.

PMID- 9273489
TI  - [Hip dislocation and fractures].

PMID- 9273488
TI  - [A case of ossifying fibromyxoid tumor].
AB  - Recently described entity: ossifying fibromyxoid tumour of soft parts is
      presented. Schwann cell nature of the proliferating cells was demonstrated by
      immunohistochemical means. This special kind of nerve sheath tumors is
      characterised by pathological differentiation of the cells, resulting bone and in
      some cases additional cartilage formation. As for biological behaviour: in spite
      of occasional histological evidences of malignancy, no distant metastases are to
      be expected. Local aggressivity and recurrences may occur, thus designation is
      preferable as semimalignant or according to more modern terms as low-grade
      malignant tumour.

PMID- 9273490
TI  - [Injury classification and surgical approach in hip dislocations and fractures].
AB  - During the last few decades, traumatic injuries of the hip joint have
      significantly increased in number, and traffic accidents have also increased.
      Depending on the speed, direction of the forces and the position of the femur at
      the moment of impact, different patterns of injury occur. Basically, they are
      classified as hip dislocations, dislocation fractures and acetabular fractures.
      These injuries have in common a high rate of concomitant lesions. Several
      classification systems have been developed for these injuries. Commonly, Stewart
      and Milford's or Levin's classification is used for dislocations and dislocation
      fractures. For acetabular fractures, Judet and Letournel's classification and its
      newer version developed by Helfet (AO classification) are generally accepted.
      Fractures of the femoral head, though included in these classifications, are
      typically described by separate classifications like the one presented in 1957 by
      Pipkin. The multitude of injuries occurring in the hip joint requires vast
      knowledge of various operative approaches. No single approach exists that would
      permit the treatment of all injuries in an ideal fashion. Approaches are either
      considered limited (Kocher-Langenbeck, ilioinguinal iliofemoral) when they permit
      access only to a restricted segment of the joint, or extended (extended
      iliofemoral, Maryland, Ruedi) when they allow all-round visualization of the hip
      joint. The choice of the best approach for an individual patient depends on the
      type of injury and also on patient variables like age, preexisting disease, and
      concomitant injuries. The decision is further influenced by the timing of
      surgery, the kind of fracture stabilization intended and by complications
      typically seen with certain approaches. The indication for extended procedures is
      only seen in patients with complex injury patterns involving both the anterior
      and the posterior column or in delayed cases undergoing surgery more than 3 weeks
      after trauma. Extended approaches permit excellent visualization of the fracture,
      but the extent of the soft tissue trauma is reflected in a high rate of
      postoperative complications. After a phase in which extended procedures were
      favored, recently a trend towards more limited approaches can be recognized
      because of their lower complication rate. This is facilitated by modern fracture
      reduction methods using indirect techniques.

PMID- 9273491
TI  - [Hip dislocation without bone injuries].
AB  - Dislocation of the hip is rare and so we regard every hip dislocation as an
      emergency until it has been reduced. From 1977 to 1996 a total of 82 patients
      with hip dislocation were treated at the Traumatic Surgery Clinic, University of
      Vienna, Austria. The average age at injury was 29 years. Some 77 patients had
      unilateral dislocation of the hip, but only in 5 cases was bilateral dislocation
      found. Iliac dislocation was most common (54 patients). Our treatment consisted
      in reduction within 6 h of the injury under general anaesthesia (Bohler) and 14
      days bedrest. Then the patients were mobilized with full weight bearing,
      depending on the pain. Of the patients 29 had no clinical infirmities, 8 patients
      reported temporarily occurring pain and in 6 patients we found a limited range of
      movement in the hip joint with occasional pain. In all, 43 patients were followed
      up after 1/2 to 19 years. Radiological signs were seen in 17 patients and
      avascular necrosis of the femoral head in 1. So after careful evaluation of the
      patients and the kind of treatment, we recommend the following: 1. Immediate,
      gentle reduction of the hip joint; 2. Bedrest for 14 days; 3. Early mobilization
      with full weight bearing.

PMID- 9273492
TI  - [Indication, technique and complications in the surgical treatment of acetabular
      fractures].
AB  - Almost 50% of acetabular fractures occur in polytraumatized patients; in over 80%
      additional injuries are found. The surgical goal is anatomical restoration of the
      acetabulum and stable fixation, in order to avoid postoperative external
      fixation. Careful clinical and radiological evaluation is essential to successful
      surgery. Standard radiological investigations include an anteroposterior view of
      the pelvis, a "spot" radiograph of the affected hip as well as obturator and
      iliac oblique views. The latter arc is especially helpful in assessing the
      central segment of the acetabulum ("dome fragment"). The documentation of any
      primarily traumatic sciatic nerve lesion is very important, and the quality of
      reduction depends greatly on the timing of surgery. The operation should be
      performed as early as possible after the surgical procedure has been carefully
      planned. A 3-D CT scan provides good information in choosing the surgical
      approach for complex fractures. In most cases, adequate reduction cannot be
      accomplished without appropriate aids. For internal fixation, both curved ASIF
      plates and straight plates are used. The operation demands a high degree of
      experience. Postoperative complications include iatrogenic nerve palsy,
      insufficient reduction, incorrectly placed implants, unstable fixation,
      redislocation, etc. With scrupulous aseptic conditions, the postoperative wound
      infection rate is low. Ectopic bone formation can occur after extensive surgical
      approaches and may, depending on size (Brooker III and IV), impair the range of
      motion of the hip. Indomethacin given perioperatively is always indicated.
      Postoperative radiation treatment should as a rule be viewed critically.

PMID- 9273493
TI  - [Hip dislocations and hip fractures--acetabular fractures. Indication, technique
      and results of conservative treatment].
AB  - Despite the great number of publications during the last 10 years concerning the
      indication, technique and results of operative treatment of acetabular fractures,
      conservative treatment still has an important role when considering the
      therapeutic possibilities. Because of the modern techniques of radiological
      imaging and improvement of diagnostic facilities, a more defined indication for
      treatment becomes possible. Conventional X-rays, completed by special projections
      like the Ala and Obturator view, and a CT scan allow determination of the
      fracture type (the Letournel/Judet classification or the AO classification). The
      most suitable treatment can then be adapted to the individual circumstances of
      the patient, i.e., age, general condition and overall severity of traumatic
      impairment. Determination of the intact part of the weight-bearing dome is
      important in selecting the most adequate therapeutic procedure. The larger the
      intact roof arc, the better the prognosis. Together with the X-ray controls
      following axial and facultative lateral extensions, the indication for
      conservative treatment can be confirmed. Early active motion of the injured limb,
      followed by walking exercises with partial weight-bearing, are important aspects
      of nonoperative treatment. Conservative treatment is recommended in non-displaced
      fractures or in fractures with little displacement, transverse fractures of the
      lower region or severely comminuted acetabular fractures with no possibility of
      reconstruction. Our clinical and radiological follow-up of 97 patients with
      acetabular fractures from the years 1981-1990 showed that the majority were
      treated conservatively (approx. 70%). The functional result after an average
      observation period of more than 70 months was good or excellent (based on the
      Merle d'Aubigne score). We feel it is important to look at operative and
      conservative treatment of acetabular fractures as two complementary non
      competitive therapeutic methods. The choice of treatment should be based on an
      exact diagnosis considering fracture type, the individual circumstances of the
      patient, and application of the necessary diagnostic facilities. Conservative
      treatment can lead to excellent long-term results.

PMID- 9273494
TI  - [Acetabular fractures in elderly persons. Primary endoprosthetic treatment].
AB  - In the Department of Traumatology at the University of Ulm, 26 elderly patients
      with displaced acetabular fractures were treated with primary implantation of a
      hip joint endoprosthesis between 1986 and 1996. The principles of operative
      therapy are stabilization of the acetabular ring, grafting of acetabular defects
      with autogenous corticocancellous bone and cranial buttressing with a reinforcing
      ring. This concept permits immediate mobilization of elderly patients and full
      weight-bearing and thus results in favorable early postoperative results.
      Secondary complications typically caused by immobilization can therefore be
      avoided.

PMID- 9273495
TI  - [Acetabular and pelvic fractures in multiple trauma].
AB  - We see pelvic fractures in about 50% of all multiple trauma patients. In many
      cases, these pelvic fractures are complicated by complex pelvic traumata, i.e., a
      pelvic fracture with pelvic vessel damage, neurological, visceral or soft-tissue
      damage, and therefore have the character of life-threatening lesions. The
      incidence of complex pelvic trauma is extremely high in cases of vertical and
      rotation instability. Most problems come from massive bleeding as a result of
      presacral venous plexus laceration. This venous bleeding usually tampons its self
      after stabilization, e.g., with an external fixator. In about half of the cases
      an immediate laparotomy is performed because of remaining circulatory
      instability, lesions of the urinary tract, or open fractures. In these cases,
      stabilization of the pelvis is frequently achieved by ORIF, e.g., plating of the
      symphysis pubis or the SI joint. Internal stabilization of the pelvis facilitates
      the following treatment in the ICU, especially when prone-supine positioning is
      mandatory due to pulmonary indications. For this reason we avoid traction
      techniques in displaced acetabular fractures, and we achieve stability with a
      joint-bridging external fixator. Treatment of complex pelvic fracture must be
      integrated in the overall concept of treatment. Differentiated and situation
      adapted action is necessary, depending on the particular situation, as well as
      the personnel and technical equipment.

PMID- 9273496
TI  - [Treatment of Pipkin fractures].
AB  - Because of the controversy that exists about therapy for the Pipkin fracture, the
      treatment and results of 117 fractures of the femoral head were reviewed and re
      evaluated at least 1 year after the trauma had taken place. The cases were taken
      from eight publications in the literature from 1983 to 1995. The lesions in this
      collection comprised 35% (n = 41) type I, 40% (n = 47) type II, 10% (n = 12) type
      III and 15% (n = 17) type IV fractures classified after the Pipkin system.
      Seventy-four percent of patients (n = 87) were operated on; only type I lesions
      were treated conservatively in 42%, thus more often than average. There were 57
      complications with equally frequent head necroses (14.5%) and severe
      coxarthritis. Coxarthritis was doubled after conservative treatment versus
      operation (23% vs. 13%). There was no difference in respect to head necrosis.
      Postoperatively, 18 (14%) periarticular ossifications were registered. Forty-one
      (75%) of 55 Pipkin I and II fractures had an at least "good" outcome; the portion
      of conservative treatment was higher than operative treatment (88% vs 69%). Still
      these results have to be seen with respect to the use of treating simple lesions
      primarily conservatively with the minimum of 6 weeks of traction therapy, thus
      counting the latter patients in this group. According to the literature, we think
      that if there are no vital contraindications, all Pipkin fractures should be
      treated operatively (early emergency operation) by reattaching bigger fragments
      and extracting smaller fragments in Pipkin I and II fractures, trying to save the
      heads in young, active patients with Pipkin III fractures in contrast to primary
      endoprosthesis in elderly patients with coxarthrosis with Pipkin IV fractures
      (unstable and displaced fractures of the acetabulum).

PMID- 9273497
TI  - [Rehabilitation following hip fractures].
AB  - In the rehabilitation of patients with acetabular fractures, we try to achieve
      anatomical reconstruction of the joint as well as unlimited mobility. This is
      important for the patient's reintegration at work and in social life. These aims
      can only be reached with joint effort of the patient him/herself and all the
      different specialists concerned with the treatment. Functional physiotherapy
      should start as early as possible after trauma. Prophylaxis of joint stiffness,
      thrombosis, pneumonia and soft-tissue ulcers due to immobilization are not only
      important in the beginning. The restoration of circulation and resorption in the
      affected tissues, in addition to creation of global sensorimotor motion patterns,
      are the main aspects of this therapy. Definite long-term success should be
      ensured by concomitant ergotherapy and well-timed measures for the patient to
      regain his/her occupational abilities.

PMID- 9273498
TI  - [Long-term results and late complications following acetabular fractures].
AB  - The long-term functional results of acetabular fractures are assessed in terms of
      the corresponding criteria of Merle-D'Aubigne and Postel (pain, mobility,
      walking). Other essential criteria include the quality of reduction and the
      radiological appearance. The age of the patient, the type of fracture and above
      all, the interval between the accident and the surgical treatment or reduction of
      the fracture must be counted among the decisive factors which influence the late
      effects of this injury. Whether or not reduction can correctly center the femoral
      head in the socket is of paramount importance, but postoperative infection or the
      development of a hematoma may also critically affect outcome. In addition to a
      report on the long-term results achieved at the Trauma Department of the
      University Hospital of Freiburg, Germany, the literature on the late
      complications of acetabular fracture is also reviewed.

PMID- 9273500
TI  - [Use of lasers in orthopedics. 3rd world congress of the International
      Musculoskeletal Laser Society (IMLAS), 7-10 November 1966, Kassel].

PMID- 9273499
TI  - [Approach-related results following acetabular fractures].
AB  - Acetabular fractures are severe injuries. Making a diagnosis and deciding on
      therapy are difficult because of the complexity of the anatomic structure and
      because of the soft tissues. Choosing the most suitable approach is the most
      important problem when deciding on the operative treatment. Besides standard
      approaches (Kocher/Langenbeck, ilioinguinal and extended iliofemoral), the
      "Maryland approach" has been established in the last few years. Modifying the
      steps of preparation, it is possible to begin the operation with a
      Kocher/Langenbeck approach (with variation on where the skin incision is made)
      and to extend the approach step by step to achieve optimal exposure. Here we
      describe the results of acetabular fractures treated between 1989 and 1994 (n =
      159) in our clinic related to the surgical approach. The "modified Maryland
      approach" as used in our clinic, starts with exposure of the dorsal column,
      offering the possibility of a universal exposure.

PMID- 9273501
TI  - [Heterotopic ossification].

PMID- 9273502
TI  - How to test the sub-unit hypothesis.

PMID- 9273503
TI  - [A model for all of Scandinavia? Guidelines for the treatment of diabetic
      nephropathies in Finland].

PMID- 9273504
TI  - [Diabetes mellitus--current Swedish national guidelines].
AB  - In 1996, national guidelines for the care and treatment of patients with diabetes
      mellitus were drawn up by specialists, in collaboration with representatives of
      the patient organisation, diabetes nurses, the professional associations of
      various medical specialties and central authorities. The national programme is
      divides into three parts: summarised information for decision-makers, clinical
      guidelines and complete information for patients. The guidelines are designed to
      provide a basis for treatment programmes at the local level. Among other things,
      the national guidelines stress the importance of the diabetes nurse both in
      primary and tertiary care, and emphasise the need of regional centers providing
      access to information and education and promoting the development of treatment.
      Another important aspect is fostering the influence of patient organisations at
      the local level, in order for the guidelines to have an impact on the quality of
      care for the individual patient.

PMID- 9273505
TI  - [Diabetic nephropathy--screening, follow-up and treatment. Nephropathy Study
      Groups of The Finnish Diabetes Organization].
AB  - Owing to advances in the diagnosis and treatment of diabetic nephropathy, its
      management has become more active and is now initiated earlier after the presence
      of microalbuminuria has been established. In 1996 the Finnish Diabetic
      Association's nephropathy group issued recommendations concerning screening for
      diabetic nephropathy, and treatment and follow-up of patients with the disease.

PMID- 9273506
TI  - [Future diabetes therapy--a personal viewpoint].

PMID- 9273507
TI  - [Electrophysiological studies of insulin secretion, physiology and
      pathophysiology].
AB  - Recent progress in experimental diabetes research is reviewed in this article.
      The application of the patch-clamp technique to the insulin-secreting pancreatic
      beta-cell has revolutionised our understanding of how an increase in the blood
      glucose concentration is linked to stimulation of insulin secretion. A major
      advance was the identification of an ATP-regulated K-channel (KATP-channel) as
      the glucose-sensitive membrane conductance of the beta-cell. Closure of these
      channels underlies the glucose-induced depolarisation of the beta-cell, which
      then triggers the opening of voltage-gated Ca(2+)-channels and the onset of
      Ca(2+)-dependent exocytosis. With the patch-clamp technique, it was also possible
      to demonstrate that the KATP-channel represents the molecular target of the
      hypoglycaemic sulphonylureas, compounds which are used clinically in the
      treatment of type 2 diabetes.

PMID- 9273508
TI  - [Relationship between education and risk factors for coronary artery disease].
AB  - Recent epidemiological studies in the western countries show an association
      between the incidence of coronary artery disease and its risk factors and
      socioeconomic status. Education is the single factor most frequently used as to
      base classification of social status. The purpose of this study was to estimate
      the association between education level and coronary artery disease risk factors
      in Iceland. The study population was 18919 individuals aged 33 to 8l who were
      living in Reykjavik and its neighbourhood. They were divided into four groups
      according to their educational level. A model of the relationship was constructed
      using linear regression analysis and the groups compared. Risk factors such as
      cholesterol, triglycerides, diastolic and systolic blood pressure, height,
      fasting blood sugar, 90 minute blood sugar, BMI and smoking were studied. In most
      cases and for both sexes there was an increased risk for those in the lowest
      educational group compared with the other groups.

PMID- 9273509
TI  - [Answer to: dyspepsia treatment program needs scientific assessment].

PMID- 9273510
TI  - [To clone or not to clone].

PMID- 9273511
TI  - [Treatment of gastric ulcer. From surgery, through antacids to antibiotics].

PMID- 9273512
TI  - [Helicobacter pylori. Which patients should be examined and treated?].
AB  - Research has shown Helicobacter pylori infections to be associated with a wide
      range of gastroduodenal diseases such as chronic gastritis, duodenal and gastric
      ulcers, mucosa-associated lymphoid tissue (MALT) lymphomas, and gastric cancer.
      Although there is no room for doubt that H pylori strains are pathogenic in
      humans, it would be premature to contend that all H pylori infections should be
      treated. The necessity of a more conservative approach is discussed in the
      article.

PMID- 9273513
TI  - [NSAID-induced ulcer and its complications].
AB  - The past two decades have seen a dramatic increase in the consumption of NSAIDs,
      despite their notorious association with serious gastrointestinal side effects.
      Of NSAID users, 20-50 per cent have an ulcer at some time; and 1-2 per cent of
      those on continuous NSAID treatment are hospitalised annually for ulcer
      complications, causing death in 10 per cent of cases, or total of 450 deaths
      annually in the Nordic countries. The risk factors are advanced age, a history of
      peptic ulcer or NSAID-induced gastrointestinal complications, high-dose NSAID
      treatment and concomitant cardiovascular disease. Ulcers can be healed with
      routine treatment, and Heliobacter pylori infection does not seem to be an
      aggravating factor. As ulcerous complications often appear without prodromal
      symptoms, prophylaxis should be considered for high-risk patients. Whereas
      histamine H2-antagonists prevent only duodenal ulcers, omeprazole seems to be
      effective against gastric and ulcers as well. The prostaglandin E1 analogue
      misoprostol protects against both gastric and duodenal ulcers, and reduces the
      risk of serious complications by 40 per cent. Newly developed NSAIDs, highly
      selective for cyclo-oxygenase 2 (COX-2), may exert potent anti-inflammatory
      effects without affecting COX-1 or the gastrointestinal mucosa.

PMID- 9273514
TI  - [Management of pregnant diabetics].
AB  - The impressive decrease in perinatal mortality rates among the offspring of
      diabetic mothers, reported from many centres during the past 50 years (Fig. 1),
      is attributed to a multiplicity of factors, in particular improvements in the
      diabetic control of prospective mothers, both before conception and during
      pregnancy. Centres for preconceptional counselling and pregnancy planning and for
      diabetic gravidae management, are to be strongly recommended. In cases where
      diabetic is diagnosed during pregnancy, the diabetic gravidae centre should
      assume responsibility for the regular follow-up of these women. Although the
      combined efforts of diabetologists, obstetricians and neonatologists have
      resulted in substantial reduction of perinatal mortality and the frequency of
      severe congenital malformations among the offspring of diabetic mothers, there
      has been less reduction in the frequency of pregnancy complications and less
      improvement in long-term prognosis for the offspring of diabetic mothers.

PMID- 9273515
TI  - [Pregnanacy counceling in nordic countries--similarities and differences].

PMID- 9273516
TI  - [The hidden starving. Nutrition in underdeveloped countries].

PMID- 9273518
TI  - [Qualitative methods in empirical health research. V. Analyzing data and coding
      procedures].
AB  - The fifth article in this series outlines a general working procedure for the
      analysis of qualitative data. Some theoretical constructs relating to the
      interpretation of qualitative data are presented first, followed by discussion of
      data processing procedures, including coding. Examples of coding and
      interpretation are given, and finally guidelines regarding data presentation.

PMID- 9273517
TI  - [Molecular mechanism in cell migration].
AB  - Lena Claesson-Welsh was awarded the Anders Jahre Prize for young scientists in
      1996 in recognition of her research into growth factors and their regulation,
      knowledge of which is important for an understanding of cancer and angiogenesis.
      The ability of cells to move along a chemical concentration gradient (chemotaxis)
      is an important property in many physiological and pathological processes, such
      as embryogenesis, wound healing and angiogenesis. In angiogenesis, whereby new
      microcapillaries are formed as sprouts from existing vessels, vascular
      endothelial cells undergo a complex three-step process. The first step consists
      in focal degeneration mediated by proteases produced by growth factor-stimulated
      endothelial cells. The next step is concomitant proliferation and migration of
      cells into the surrounding tissue. Finally, the cells differentiate to form a
      continuous lumen. Tumour growth is strictly dependent on angiogenesis. Many
      tumours produce the growth factor. VEGF, which exerts its effect on receptor
      tyrosine kineases which are expressed on endothelial cells, thus stimulating
      endothelial cell chemotaxis toward the tumour. The regulation of endothelial cell
      migration in this pathological process would be of great therapeutic value.

PMID- 9273519
TI  - [Herpes zoster--clinical aspects].
AB  - Clinical course of herpes zoster was assessed in 119 immuno-competent and in 28
      immuno-compromised hosts. Complications of herpes zoster were observed in one
      third cases. However, the frequency of post-herpetic neuralgia was lower than
      that seen by other authors. Despite severe underlying diseases in compromised
      hosts, good outcome of herpes zoster was obtained. It may be related to the use
      of aciclovir in all these cases. Early and rational treatment with aciclovir is
      important for decreasing of the frequency of severe complications of herpes
      zoster.

PMID- 9273520
TI  - [Analysis of selected parameters of damage to the liver during the course of tick
      borne encephalitis].
AB  - In 1993, 80 patients (43 female and 37 male) with tick-borne encephalitis were
      hospitalized in Clinic of Neuroinfections and Parasitic Diseases of Medical
      School in Bialystok. 6 (7.5%) patients were jaundiced, 16 (20%) had hepatomegaly.
      We noticed increased enzymatic activity of aspartate aminotransferase (x = 74.5
      U/l) in 9 (11.25%) cases, alanine aminotransferase (x = 89.5 U/l) in 11 (13.75%)
      cases, increased level of bilirubin in blood (from 1.4 to 3.5 mg/dl) in 7 (8.75%)
      cases. Protein level in blood was average x = 5.95 g/dl, percentage of albumin
      was average x = 48.61%, globulin--x = 14.62%. Prothrombin index and ammonia blood
      level were in normal range. Observed pathological changes were transient and
      referred mainly to patients with severe clinical course of disease.

PMID- 9273521
TI  - [Epidemiologic and clinical characteristics of Lyme borreliosis in northeastern
      Poland].
AB  - Lyme borreliosis (LB) caused the tick-borne spirochete B. burgdorferi, is
      associated with a wide variety of manifestations including dermatologic,
      rheumatologic, neurologic and cardiac abnormalities, that can differ from one
      region to another. To define clinical picture of LB in Poland, particularly in
      north-eastern region, we studied in 46 patients. Diagnosis of LB was established
      according to criterion, including serological confirmation with ELISA LB seems to
      be disease, which renal prevalence in Poland is higher, than it was primarily
      estimated. Clinical picture of the disease does not differ significantly from
      observed in other parts of the world. The only, but important exception is more
      frequent manifestation of B. burgdorferi infections with meningitis or/and
      encephalitis (48% of patients).

PMID- 9273522
TI  - [Results of determining antibodies against Borrelia burgdorferi in patients with
      limited scleroderma].

PMID- 9273523
TI  - [Use of human anti-Pseudomonas immunoglobulins in treatment of children with
      burns].
AB  - This studies included 15 children with burns involving 10-55% of the whole body
      surface, treated at the two surgical departments in Poland. All patients have
      been given 0.5 mL of a 15% solution of anti-Pseudomonas immunoglobulin in a deep
      i.m. injections for 3 consecutive days. Immunoglobulin has generally been well
      tolerated, except short fever attacks. Human anti-Pseudomonas immunoglobulin
      prepared in the institute of Haematology and Transfusion in Warsaw prevented
      infections with P. aeruginosa in 12 burned children. There have been no cases of
      bacteremia produced by P. aeruginosa in 15 treated children with burns. The
      obtained results indicate efficacy of such therapy in burned children.

PMID- 9273524
TI  - [The effect of discontinuing intravenous opiate injections and methadone
      treatment on the status of the immune system in narcotic abusers with HIV].
AB  - The effect of discontinuation of injecting drug use and administration of
      methadone was investigated in 43 HIV-infected drug abusers. In 20 (46.5%) out to
      them an improvement in the immune status as measured by CD4+ lymphocyte
      percentage and CD4/CD8 lymphocyte ratio was observed, while remaining 23 persons
      (53.5%) showed stable or decreasing values of both parameters. In the control
      group which consisted of 23 persons who continued injecting drug use, only 3
      (13%) out of the showed increase in the CD4+ lymphocyte percentage and CD4/CD8
      lymphocyte ratio. It seems that discontinuation of injecting drug use may improve
      the function of immune system in HIV-infected drug addicts and could be an
      important factor in the approach for treatment of these patients.

PMID- 9273525
TI  - [Antibody avidity in diagnosis of toxoplasmosis].
AB  - The sequential changes in avidity of antibodies to Toxoplasmosis gondii were
      investigated. The values of avidity were observed to be significantly lower in
      serum samples drawn in early stages of infection than 3-4 months later and
      increasing with time of duration of the infection. A correlation was found
      between antibody avidity and antibody level measured in international units
      (IU/l), whereas, no correlation was observed between avidity, IU/l and antibody
      titers.

PMID- 9273527
TI  - [Multiorgan changes in AIDS in a reported case].
AB  - The clinical course of HIV infection and results of autopsy examination in 49
      years old patient was shown. The attention was paid to difficulties of diagnosis
      of opportunistic infections in a patients with advanced HIV disease. Variety of
      infectious factors, that could affect a patient with significant immunodeficiency
      was outlined.

PMID- 9273526
TI  - [Efficacy of cimetidine in treatment of Herpes zoster in the first 5 days from
      the moment of disease manifestation].
AB  - 221 patients with Herpes zoster have undergone the treatment. They were given
      cimetidine in the daily dose 3 x 200 mg and 1 x 400 mg to night. It was proved
      that the efficacy of the Herpes zoster treatment by cimetidine is inversely
      proportional to the time of the disease duration. The authors suggest to use
      cimetidine in the treatment of Herpes zoster virus infections even during the
      prodromal period.

PMID- 9273528
TI  - [Tuberculosis of the lymph nodes with esophageal-cutaneous fistula in a patient
      with AIDS].
AB  - A case of patient with the tuberculosis of lymph nodes and esophago-cutaneous
      fistula in the course of AIDS has been presented. A valve has been formed within
      fistula enabling to visualize a free passage only after an oral contrast
      administration. It is worth noting that tuberculosis frequently accompany severe
      course of AIDS.

PMID- 9273529
TI  - [Modern diagnostic methods for tuberculosis].

PMID- 9273530
TI  - [Treatment of poisoning with Amanita phalloides--facts and controversies].

PMID- 9273531
TI  - [The pineal gland and the immune system].

PMID- 9273532
TI  - [Humanization of medical studies and the development of empathy in medical
      students].

PMID- 9273533
TI  - [Are fathers helpful, harmful or superfluous for the development of
      adolescents?].

PMID- 9273534
TI  - [The contribution of fathers to the individuation process in adolescence].
AB  - Numerous studies have shown fathers to be less engaged and less involved with
      their children and adolescents. This paper discusses the possible function that
      fathers' lower involvement may play in the development of their children. Data
      from two studies conducted on adolescents show that on the one hand fathers spend
      less time and are less engaged with their adolescents, but when they are
      together, the nature of their interaction is distinctive. For example, fathers
      are more engaged in play-like activities. This apparently distant and distinctive
      model is what adolescents need at this period of separation--a model of a "close
      enough" parent that allows and respects separation and support strivings for
      individuation. As results show, adolescents are satisfied with the role fathers
      play in their lives. Moreover, fathers are perceived as models for subsequent
      developmental goals such as marital life. It is suggested that fathers in their
      natural attitude are more capable of balancing closeness and separateness than
      mothers do and as such they are more flexible in response to varying
      developmental goals of their adolescent offspring.

PMID- 9273535
TI  - [Idealization of the father: a necessary consequence in divorce families?].
AB  - In a sample on 243 adolescents, it was investigated whether idealization is a
      necessary consequence for adolescents experiencing parental divorce. Earlier
      studies emphasized the negative effects of parental divorce on the development of
      children and adolescents. Due to historic changes in family structure, however,
      parental divorce has to be conceptualized in more positive terms. In the study
      presented, idealization of the non-custodial father was only found in a clinical
      subsample of adolescents, whereas the father-adolescent relationship in non
      clinical adolescents from divorced families did not differ significantly from the
      quality of relationship described by non-clinical adolescents living in two
      parent families. The function of idealization in coping with negative affects
      such as aggression and affliction is discussed, in particular for those
      adolescents in the clinical sample who rarely have contact with their non
      custodial fathers, and the contributions of fathers to hold up this idealization
      outlined. Idealistic conceptions in adolescents of divorced parents are
      especially problematic, since adolescents are expected to become disengaged of
      their parents and develop a mature and realistic perception of them.

PMID- 9273536
TI  - [Role of the father in family communication: findings of a longitudinal study of
      healthy and chronically ill adolescents].
AB  - In this contribution, family communication processes were analyzed in a sample of
      families caring for chronically ill adolescents compared to families with healthy
      adolescents. Fifty-five families had to solve the FIT two times, in 1991 and in
      1993. Results elucidated an atmosphere of consensus, in families with chronically
      ill adolescents as well as a tendency to discuss less options than in families
      with healthy adolescents. Fathers in particular disagreed rarely and gave only
      indirect suggestions. In contrast, families with a healthy adolescent showed more
      vivid discussion and more individuality. Over the time, in all families, fathers
      emphasized increased separateness with their adolescents, irrespective of the
      gender of the child.

PMID- 9273537
TI  - [Significance of family relations for coping with psychological disorders-
      results of an empirical study of therapy prognosis of children and adolescents
      with psychological disorders].
AB  - The importance of family relations for the therapy of psychiatric disorders in
      children and adolescents is discussed reporting results from an empirical study
      carried out in an inpatient sample of a child and adolescent psychiatric unit
      with regard to the quality of mother-child resp, father-child relation and its
      influence on coping processes. Whether adolescents suffering from a psychiatric
      disorder are able to cope with their problems during the course of a therapy,
      depends on their individual and social resources. Therapy outcome is to a great
      extent influenced by the emotional quality of their family relations. Hostility
      and rejection as well as unstructured and disorganized parental behavior
      contribute to a negative outcome. A differentiated analysis shows further that
      the relation between the adolescents and their fathers is particularly important
      for therapy prognosis. Nevertheless, one has to consider the respective relations
      with both parents for therapy prognosis, as problems with one parent may be
      partly compensated by a good relationship with the other parent. Finally, the
      cooperation between parents and clinical staff is discussed. Data and experiences
      show that interest and readiness of parents (mothers as well as fathers) for a
      close cooperation are higher than generally expected.

PMID- 9273538
TI  - [Diagnosis of cytomegalovirus disease in biopsy and surgical material. Methods
      and clinical relevance].
AB  - Since the first description of cytomegaly as "disease with protozoan-like cells"
      more than 50 years have past until a definitive explanation of the viral
      aetiology was reached. In the eighties cytomegaly gained increasing importance in
      adults. This event was based upon the occurrence of cytomegaly especially in
      patients with organ transplantation, AIDS infection, chronic dialysis or
      chemotherapy of malignant tumours. With the development of immunohistochemistry
      (IHC), in situ hybridization (IHS) and polymerase chain reaction (PCR) new, more
      sensitive methods became available to detect CMV infections especially in biopsy
      specimens or cytological material. With IHC, ISH and PCR CMV verification is
      possible in seemingly normal cells without inclusion bodies. PCR can be used also
      on small biopsy particles of paraffin-embedded material and is characterized by
      high specificity and sensitivity. The parallel performance of IHC and ISH was
      proved to be useful in routine diagnostic work, whereas PCR should be used
      especially in diagnostically different cases. The methods of the evidence of CMV
      infection are analysed in the different organs.

PMID- 9273539
TI  - [Atherosclerosis. Formal pathogenesis, classification and functional
      significance].
AB  - Atherosclerosis and its complications determine the majority of deaths in the
      western world, followed by malignant tumors. The present work introduces a
      classification of stages of atherosclerotic disease based on relevant pathogenic
      and therapeutic concepts, elaborated by H. Stary. At the present, we are able to
      relate different lesion types to a time course and partly to interferences
      between participating cell populations as well as to special pathogenic stimuli.
      From the therapeutic view, this knowledge is fundamental for preventive as well
      as interventional strategies like gene therapy. Distinct atherosclerotic plaques
      reveal a different composition and architecture, which may account for the
      variable risk for further complications of lesions showing the same size and
      degree of stenosis. In combination with an advanced clinical and diagnostic
      characterization of atherosclerotic lesions, the present concept might contribute
      to a better and differential therapy of atherosclerosis.

PMID- 9273540
TI  - [Hyperplastic polyps of the colon. An inhomogeneous group of pathologic-anatomic
      changes].
AB  - A total of 334 hyperplastic polyps of the colon of 266 patients were examined
      under epidemiologically, morphometrically and histochemically. Of these, 62 cases
      (23%) were associated with adenomas, 18 cases (7%) with carcinomas. Hyperplastic
      polyps are not entirely homogeneous, pathologically and -anatomically: Carcinoma
      associated hyperplastic polyps are larger in diameter, the size and width of
      their crypts is greater, and they have a higher percentage of goblet cells with a
      higher amount of sialomucins as shown by HID/AB stain.

PMID- 9273542
TI  - [Heart rupture after mitral valve replacement. Pathologic-anatomic findings].
AB  - The rupture of the free left ventricular wall is considered a serious
      complication following mitral valve replacement. We report about 3 cases
      characterized by similar pathologic-anatomical findings within the region of the
      left ventricle after mitral valve replacement. Following resection of the
      original and pathologically altered mitral valve and implantation of a
      prosthesis, rupture of the left ventricular wall occurred in short time intervals
      ranging from 1 to 12 h postoperatively. All cases represented a transverse
      midventricular disruption located between the mitral valve anulus and the
      resected papillary muscles. The histologic findings included necrotic, damaged
      myocardial structures with considerable bleeding to the interstitium.
      Inflammatory infiltration could be detected within the myocardial defects.
      Abnormal pathologic findings of the coronary arteries or intraoperative lesions
      could be excluded by thorough autoptic studies. Because of central localization
      of the ventricular disruption between the mitral valve anulus and the papillary
      muscles a direct traumatic myocardial injury caused by mitral valve orotheses is
      to be excluded. When taking into account several reports from literature in
      combination with our described findings, in autopsy, a loss of contractile
      integrity of the left ventricle following resection of mitral valve apparatus,
      especially the chordae tendinaea, should be considered as primary cause for this
      type of ventricular rupture. This destabilization will lead to a regionally
      stressec myocardial "stretching" which finally results in rupture of the left
      ventricular free wall. The described pathogenetic concept seemingly represents
      the decisive mechanism of this transverse midventricular disruption in all 3
      cases. To prevent such post-operative complications, only very limited resection
      of the mitral valve apparatus should be performed to maintain parts of the
      chordae tendineae.

PMID- 9273541
TI  - [Malignant non-epithelial tumors of the pancreas].
AB  - Nonepithelial malignant tumors of the pancreas are extremely rare neoplasms with
      a frequency of approximately 0.6%. They are always explored because of a
      suspected diagnosis of pancreatic carcinoma. Amongst the more than 600 primary
      pancreatic neoplasms in our pancreatic tumor archive only 5 neoplasms were of
      nonepithelial origin (one was a malignant peripheral nerve sheath tumor [MPNST],
      one a leiomyosarcoma, one a malignant mesothelioma, and two were peripheral
      neuroectodermal tumors [PNET]. The differential diagnosis includes secondary
      infiltration of the pancreas by mesenchymal tumors of the retroperitoneum,
      undifferentiated pancreatic carcinoma and, especially in the case of PNET,
      malignant lymphoma. Preoperative chemotherapy and down-staging can improve the
      operability and prognosis, especially in PNET.

PMID- 9273543
TI  - [Intramural hemangioma of the portal vein].
AB  - Capillary hemangiomas occur rather ubiquitously, but extremely rare within the
      wall of blood vessels. For this reason the authors report on a small capillary
      hemangioma of sinusoidal type. It has been observed fortuitously within the wall
      of the portal vein at autopsy of a 79-year-old woman. Based on site and
      structural characteristics the benign neoplasia is supposed to have developed
      from a local malformation, probably an abortive liver anlage.

PMID- 9273544
TI  - [Atypical morphologic lung manifestations of Pneumocystis carinii infection in
      AIDS patients].
AB  - We report on unusual presentation forms of Pneumocystis carinii infection of the
      lung in two patients with AIDS. A 36-years-old woman presented a cavitation in
      the lung middle lobe and bullous changes in the apical portion of the right upper
      lobe on the chest x-ray. The biopsy of these lesions was not diagnostic and the
      patient was operated on. The surgical specimen of the removed lung segment showed
      a cavitary lesion with a border of granulation tissue with giant cells, focal
      recent and older hemorrhages, rests of fibrinous exudate and dystrophic
      calcifications. In the surrounding tissue there were Pneumocystis carinii in the
      alveolar spaces and also in the alveolar walls, this tissue invasion through the
      organisms being most probably the cause of the cavitary change. A cytomegalic
      virus infection was also found. A 30-years-old man presented patchy pulmonary
      infiltrates on his x-ray. The examination of bronchial secretion and bronchial
      washing specimens revealed P. carinii. In addition, the organisms were
      demonstrated in the walls of pulmonary vessels and in the stroma of the bronchial
      mucosa on the biopsy. In a sample of lung tissue which was taken after death,
      there were no Pneumocystis carinii anymore, but some proliferations of connective
      tissue with giant cells and calcification, which could represent residual changes
      of the Pneumocysts carinii infection. Besides, persisting changes of cytomegaly
      were found. We conclude that a Pneumocystis carinii infection should be
      considered in all HIV-positive or AIDS patients with any kind of lung lesions.

PMID- 9273546
TI  - [Fulminant infection outcome after splenectomy].
AB  - A report is given of two patients with a history of splenectomy many years
      previously due to traumatic rupture. No vaccination was given to either patient.
      From a state of good health, both patients developed fulminant, therapy-resistant
      sepsis with proof of Streptococcus pneumonlae in the blood culture. Autopsy
      findings were similar to Waterhouse-Friderichsen-syndrome. In conjunction with
      the history of splenectomy, the final pathological diagnosis was a so-called OPSI
      syndrome. This postsplenectomy sepsis is discussed further.

PMID- 9273545
TI  - [Association of bone marrow mastocytosis with extremely immature extramedullary
      mast cell sarcoma].
AB  - The case of a 63-year-old man with a widespread retroperitoneal tumor and two
      tumor nodules in the left testis is described. Histopathological and
      cytopathological examination of tissue from the retroperitoneal tumor led to a
      diagnosis of lymphoreticular neoplasia. The patient died in acute cardiac
      failure, five weeks after initial presentation. Autopsy revealed another tumor
      nodule in the right atrium. Macroscopically, the bone marrow appeared normal. The
      tumor cells were reactive for CD45, vimentin and chloroacetate esterase, but were
      uncreative with a broad spectrum of antibodies against myelomonocytic and
      lymphocytic antigens and antibodies against tryptase and c-kit (CD117),
      characteristic markers for mast cells. However, the bone marrow exhibited the
      typical picture of mastocytosis. A diagnosis of bone marrow mastocytosis with an
      associated secondary extramedullary mast cell sarcoma was established. The cause
      of death was heart failure due to arrhythmia caused by an exophytic atrioseptal
      tumor nodule.

PMID- 9273547
TI  - [Immunohistochemistry Circle Trial of the University Institute of Pathology in
      Germany].

PMID- 9273548
TI  - Which analgesia? Guidelines to pharmacological pain control.
AB  - The aim of this guide is to provide an accessible resource for nursing and
      medical staff on current pharmacological methods of pain control-the different
      types of analgesics that are available, the indications for each and their doses,
      formulations, contraindications and side-effects. The focus is on the drugs used
      in the management of postoperative pain, although their uses obviously extend to
      the management of other types of pain, such as chronic pain, cancer pain or pain
      relief during palliative care. Patient-controlled analgesia and the management of
      pain in children are not included in this guide.

PMID- 9273549
TI  - UVB DNA dosimeters analyzed by polymerase chain reactions.
AB  - Purified bacteriophage lambda DNA was dried on a UV-transparent polymer film and
      served as a UVB dosimeter for personal and ecological applications. Bacteriophage
      lambda DNA was chosen because it is commercially available and inexpensive, and
      its entire sequence is known. Each dosimeter contained two sets of DNA sandwiched
      between UV-transparent polymer films, one exposed to solar radiation
      (experimental) and another protected from UV radiation by black paper (control).
      The DNA dosimeter was then analyzed by a polymerase chain reaction (PCR) that
      amplifies a 500 base pair specific region of lambda DNA. Photoinduced damage in
      DNA blocks polymerase from synthesizing a new strand; therefore, the amount of
      amplified product in UV-exposed DNA was reduced from that found in control DNA.
      The average lesion frequency per 500 base pair per strand at 16 PCR cycles was
      approximately 1.22, 1.00, 0.70 and 0.50 for 30 ng, 50 ng, 100 ng and 150 ng of
      dried DNA, respectively, after a total dose of 60 kJ m(-2) delivered with a solar
      UVB simulator. Although the average lesion frequency increases linearly with
      increasing doses for four different amounts of template DNA, the lesion frequency
      seems to be averaged by the amplified products from the protected lambda DNA
      molecules below the top few layers. The average daily dose, equivalent to the UV
      dose applied with the solar UVB simulator was 10.2 +/- 0.4 kJ m(-2) with the 50
      ng containing DNA dosimeter in September 1995 in Melbourne, FL. Both 50 ng and
      150 ng containing DNA dosimeters produced the same average daily dose within
      experimental error in January 1996, which was 5.2 +/- 0.3 kJ m(-2) at the same
      location. The dried lambda DNA dosimeter is compact, robust, safe and
      transportable, stable over long storage times and provides the total UVB dose
      integrated over the exposure time.

PMID- 9273550
TI  - [Psychotherapeutic responsibilities in psychiatry--and the cooperation of
      fields].
AB  - In the context of discussions on the re-organisation of specialities in
      psychiatry and psychological therapy recent studies on the prevalence of
      psychogenic disorders in different psychiatric institutions are presented and
      compared with the communications available so far. Despite the availability of
      excellent psychotherapeutic care units, more than one third of the patients in
      psychiatric units suffer from psychogenic disorders (inpatient units 30 per cent,
      outpatient and emergency units 45 per cent). This leads to an increasing demand
      on the competence and responsibility of the psychiatrist. Focus is on three main
      issues. It follows that the psychiatrist must also be conversant in
      psychotherapy. The advantages of combining and coordinating both fields during
      specialist training are discussed in this paper.

PMID- 9273551
TI  - [Psychoeducational family treatment in schizophrenia--a popular concept? A
      critical evaluation of different treatment models].
AB  - Having outlined the background of psychoeducational intervention in the treatment
      of schizophrenic disorders the goals of family psychoeducation and of
      psychoeducation are described. Two formats of family psychoeducation are
      discussed to illustrate the differences in form of intervention. Especially the
      underlying illness concept and anthropology are critically assessed: it is worth
      nothing that patients and relatives are provided with a somatic illness concept
      not consistent with current research evidence and which may support passive
      illness-management strategies. Finally, the reduction of psychoeducational
      treatment to the improvement of medication compliance is discussed.

PMID- 9273552
TI  - [Changes in the structure of an Alzheimer family group].
AB  - The family of Alzheimer patients is in general deeply engaged in caring for the
      patient and is faced by enormous physical and psychological stress. Today in
      Germany there are more than 100 groups of family members caring for Alzheimer
      patients. These groups are either headed by an expert, layman, or supported by
      experts. The Tubingen Alzheimer group has gone through all three stages since its
      foundation in 1991. Experience gathered with these different forms of
      organisation are reported.

PMID- 9273553
TI  - [Quality assurance in inpatient treatment of depression. Aspects of quality
      monitoring and external quality assurance exemplified by a pilot project of
      inpatient treatment of depression].
AB  - Aspects of a Pilot Study on Depression Treatment According to Quality Monitoring
      and External Quality Assurance: Experiences and results of a pilot study on
      quality of the treatment of depressed inpatients in 4 different psychiatric
      hospitals (2 state mental hospitals, 1 university clinic, 1 psychiatric clinic at
      a city general hospital) according to so-called process and outcome quality, are
      reported. Outcome data (self-ratings, observer rating, clinical global impression
      admission versus discharge, patient satisfaction with treatment, duration of
      inpatient stay/and patient data are reported while comparing the 4 hospitals.
      Difficulties and problems of data collection, assessments and comparison of 4
      different hospitals are discussed.

PMID- 9273554
TI  - [Psychiatric consultation service at the Psychiatric Clinic of the Gorlitz
      Municipal Clinic GmbH, ECLW].
AB  - The Psychiatric Hospital at the Municipal (General) Hospital in Gorlitz, Germany,
      was the only Department of Psychiatry in a non-University (general) hospital in
      the newly integrated German provinces who were originally part of the so-called
      "German Democratic Republic" before the re-unification of Germany, to participate
      in the German collective study on "Psychiatric and Psychosomatic Consultation and
      Liaison Service in German General Hospitals-A Multicentre Empirical Study to
      Assess and Evaluate Existing Structures and Services". This study is an
      independent part project that includes specific questions forming part of the
      European collective study on "Effectiveness of Mental Health Consultation and
      Liaison Service Delivery in the General Hospital".

PMID- 9273555
TI  - [Prejudice and judgment: psychiatric consultation from the viewpoint of the
      patient].
AB  - 187 general hospital patients were questioned in a prospective study with a
      semistructured interview about their subjective experience and assessment of the
      psychiatric consultation. Over 40% complained that they had been given
      insufficient information about the psychiatric consultation by their primary care
      physician. It was rarely (10%) found to be unpleasant, and 46% of the patients
      specifically stated that it had been valuable. In order to improve the efficiency
      of the psychiatric consultation more attention should be paid to the subjective
      judgement of the patients.

PMID- 9273556
TI  - [A program for the rehabilitation of mentally ill students].
AB  - The rehabilitation of mentally ill undergraduates is a neglected area. The scope
      and relevance of this problem are confirmed by the epidemiological figures
      available. A programme aimed at supporting mentally ill undergraduates at Munster
      university offers such students psychoeducationally oriented group therapy and
      intensive individual counselling. The report covers 82 students who have
      expressed interest in this programme since the 1993 summer semester. 57 took part
      for at least 1 semester, the majority of them (56%) being schizophrenic patients.
      The main problem is in structuring and coping with required standards of
      performance, social isolation, excessively high expectations of their own
      achievement potential, and insecurity with regard to the prospects of success in
      their degree courses. Experience to date confirms the need for, and the
      opportunities offered by on-target support of mentally ill undergraduates.

PMID- 9273557
TI  - [Electroconvulsive therapy, electroshock and shock therapy in the newspaper].
AB  - Newspapers reports on ECT are extremely biased. A quantitative analysis of four
      German and Swiss papers demonstrates impressingly the change of meaning of
      synonymous terms like "Elektroschock" and "Schocktherapie" which refer to torture
      and brutal reforms of Eastern European communist economies.

PMID- 9273558
TI  - [Follow-up of a "culture-bound psychosis"].
AB  - Today it is uncontested that some psychiatric disorders like schizophrenia occur
      transculturally despite their culture-dependent symptomatical variations. In the
      following text we discuss the case of a Chinese patient emigrated to Switzerland.
      Different culture-dependent appreciation of facts and therapeutic approaches by
      her family and by the treatment team influenced the course of the psychotic
      disorder.

PMID- 9273560
TI  - [Only a gait disorder? A case report of dissociative disorders].

PMID- 9273559
TI  - [Acute delusional psychosis and neuroleptic malignant syndrome after emigration
      of a Russian German patient].
AB  - Emigration is often followed by psychic disorders. The special issue of Germans
      from the GUS-States immigrating to Germany is presented. The modus of paranoid
      reaction is discussed along the biography and the criteria of ICD 10. The acute
      paranoid psychosis was complicated by a neuroleptic malignant syndrome.

PMID- 9273561
TI  - [When blind patients see...--(atypical) Charles-Bonnet syndrome].

PMID- 9273562
TI  - [Folie a deux in depressive disorders].

PMID- 9273563
TI  - [Psychotherapeutic sequence in treatment of chronic schizophrenic patients].

PMID- 9273564
TI  - Comparison between the Rorschach Depression Index and depression-related measures
      in a nonpatient sample.
AB  - The Rorschach Depression Index of Exner was correlated with eight self-report
      measures of affect and related personality constructs, including the Beck
      Depression Inventory, the Multiple Affect Adjective Checklist-Revised Depression
      and Positive Affect scales, and Kaplan Self-derogation in a sample of 41
      undergraduates (M age 19 yr.). The only significant correlation was an unexpected
      inverse correlation (r = -.35) for scores on Kaplan Self-derogation, suggesting
      the need for caution in the use of the Depression Index as an indicator of
      depression in nonpatients.

PMID- 9273565
TI  - [The absence of Yersinia enterocolitica in foods and animal reservoirs in areas
      of the state of Pernambuco, Brazil].
AB  - A search for the presence of enteropathogenic bacteria in fresh vegetables
      obtained in 5 restaurants from the city of Recife, revealed neither Yersinia
      enterocolitica nor other pathogenic bacteria in 96 samples analyzed. Furthermore,
      Y. enterocolitica was not found in the oral and rectal swabs taken from 15
      apparently healthy pigs at an abattoir in the municipality of Bonito in the
      Pernambuco State. Another search in which twenty one rodents from four species
      and one marsupial specimen were examined did not detect the presence of Yersinia
      and other enteropathogenic bacteria.

PMID- 9273566
TI  - [Triatomids and forest reservoirs of Trypanosoma cruzi in the state of Parana,
      southern Brazil. Preliminary results].
AB  - In the rural area of five municipalities of the Northeast of the State of Parana,
      Brazil, 154 adults or nymphs of Triatoma sordida and 2 Panstrongylus megistus
      were captured in 21 (41.2%) of 51 dwellings at the peridomestic sites.
      Trypanosoma cruzi-like organisms were found in 58 out of the 135 (43.0%)
      triatomids. Moreover, it was also found in the blood of 4/7 opossum (Didelphis
      sp). The triatomine infestation was more prevalent in the peridomicile than
      inside house. The forsaken wooden house presented the highest level of
      infestation (53.8%). Although the rural area of the Northeast of the State of
      Parana is considered under epidemiologic surveillance it still presents a high
      level of peridomestic infestation by triatomids highly infected with T. cruzi
      like organisms.

PMID- 9273567
TI  - [The clinical evaluation of quinine for the treatment of Plasmodium falciparum
      malaria].
AB  - Quinine was the first antimalarial drug to be employed and also the first
      resistance was noticed to. After 1960 quinine urged to be reintroduced in routine
      therapy alone or in combination. Aiming at evaluating the effectiveness of
      different schedules we studied 484 patients seen at the Malaria Laboratory. We
      used quinine alone in 126 patients, quinine plus sulfadoxine and pyrimethamine in
      119 patients and quinine plus tetracycline in 239 patients. The results shown
      that 81% of all patients were treated with success and only 0.6% were R2. and
      there is no R3. We emphasize a high resistance rate to quinine either alone
      (23.1%) or associated to sulfadoxine and pyrimethamine (37.8%). A higher
      resistance rate seen with the combination might be linked to the smaller dose of
      quinine used in that instance. It is worth noting the high cure rate with the
      quinine-tetracycline association.

PMID- 9273568
TI  - [The evaluation of the efficacy of artesunate combined with tetracycline in the
      therapy of falciparum malaria].
AB  - A controlled clinical therapeutic study in hospitalized patients compared
      artesunate with quinine and mefloquine in patients with uncomplicated falciparum
      malaria. Forty two patients entered the trial and the follow up was for 28 days
      with thick blood film taken every 12 hours until became negative. Laboratory
      examinations included haematological and biochemical tests before and after
      treatment. Patients had a mean parasitaemia of 42.568 per microliter. Twenty six
      patients completed 28 days of follow up but 16 did not fulfil this protocol. One
      in each of the therapeutic groups showed delayed R I resistance. A further
      patient in the quinine group showed R III resistance. The cure rate was 88.8% for
      artesunate. 85.7% for mefloquine and 81.8% for quinine; no significant difference
      was found, the same occurring with the clearance of fever. The artesunate group
      had a quicker parasitaemia clearance time (37.3 +/- 11.5 hours) when compared
      with quinine (65.2 +/- 17.4) showing a significant difference (p = 0.0016).
      Parasite clearance with mefloquine, was intermediate (58.9 +/- 16.6 ours) between
      the artesunate and quinine. No important side effects were observed with any of
      the therapeutic regimens and no deaths registered.

PMID- 9273569
TI  - [A therapeutic trial in Giardia muris infection in the mouse with metronidazole,
      tinidazole, secnidazole and furazolidone].
AB  - A comparative study about the effectiveness of metronidazole, tinidazole,
      secnidazole and furazolidone was performed on Giardia muris from mice naturally
      infected. Groups of 12 animals each was constituted: the control treated with
      saline; one treated with metronidazole; one treated with furazolidone; one
      treated with tinidazole; one treated with secnidazole; histological normal
      control; histological infected. Samples of three stools were examined before and
      after treatment with quantification of cysts. Animals were cured when the
      trophozoites was not seen in the small bowel. The curative activity of drugs was
      58.3% for metronidazole, 50% for furazolidone, 40% for secnidazole and 16% for
      tinidazole. It was also showed that there was a different pattern of the
      intestinal mucosa from the control and infected groups, treated or not,
      suggesting that the alterations encountered in the mucosa of infected animals
      were due to the parasitism either the action of the drugs.

PMID- 9273570
TI  - [Diethylcarbamazine in the treatment of Bancroft's filariasis].
AB  - The authors presented a detailed review about the treatment of bancroftian
      filariasis with diethylcarbamazine. The interesting aspects about the drug
      discovery and the basic concepts about its pharmacology were reported in a
      summarised form. On the other hand, emphasis was made about the speculation done
      by several authors about the intriguing findings regarding its efficacy reported
      in the literature. Latter, it was brought the new advances about the disease, as
      for example, the visualization by ultrasound of living Wuchereria bancrofti adult
      worm on its natural host--the human being. This made possible the comprehension
      of several paradoxical issues reported, focusing the treatment of infection using
      diethylcarbamazine. So far, because of the lack of ideal drug with micro and
      macrofilaricidal properties, together with the new understand about the disease
      and the new parameters for monitoring the efficacy of the drug,
      diethylcarbamazine has back its importance conquered at the begin of its
      discovery, almost fifth years ago.

PMID- 9273571
TI  - [Persistent neutrophilic meningitis in a patient with the acquired
      immunodeficiency syndrome].
AB  - Persistent neutrophilic meningitis is rarely found and it is characterized by
      predominance of the number of neutrophils in samples of C SF (cerebrospinal
      fluid) from the patient after seven days of treatment. The above patient in HIV
      positive; he has developed fever and mental disorder for 4 months and has
      presented neutrophilic pleocytosis in analysis of CSF for more than 5 months.
      Since the beginning or the treatment he has taken antituberculous drugs and
      corticosteroids. For 3 months, the serologic evaluation, smears and cultures were
      negative. On the 60th day in hospital, the investigation of acid-fast bacilli in
      CSF was positive and culture confirmed the presence of Mycobacterium tuberculosis
      resistant to isoniazid. Several factors that may have caused this uncommon
      development were discussed: the disturbance of cell-mediated immunity, mainly in
      release of IL 8 and TNF, the simultaneous use of medicines that could alter the
      CSF concentration of antituberculous drugs, and the increasing number of
      multiresistant strains.

PMID- 9273573
TI  - [Rochagan].

PMID- 9273572
TI  - [The metacyclogenesis of Trypanosoma cruzi as a parameter of parasite interaction
      with the triatomid vector].

PMID- 9273574
TI  - [Houses of Fire].

PMID- 9273576
TI  - [Diagnosis of tuberculosis. De rerum harmonicarum between the clinic and the
      lab].

PMID- 9273575
TI  - [The future of tuberculosis: fewer drugs, less time].

PMID- 9273577
TI  - [Clinical interest of a new simple system for isolating Mycobacterium
      tuberculosis].
AB  - BACKGROUND: A new system, Mycobacteria Growth Indicator Tube (MGIT), was used for
      the recovery of M. tuberculosis from clinical specimens, which was compared with
      conventional methods of microbiological methods. The MGIT system consists of
      tubes containing liquid medium and a fluorescent oxygen consumption sensor to
      detect bacterial growth. METHODS: A total of 197 clinical specimens from 162
      patients with clinical suspicion of tuberculosis were processed in parallel and
      seeded in the new system, the radiometric system BACTEC and Lowenstein. RESULTS:
      The validity criteria for the new system were: sensitivity, 95.4%; specificity,
      100%; negative predictive value, 89.3%, and positive predictive value, 100%. The
      greatest clinical agreement occurred with MGIT and BACTEC. The mean time up to
      diagnosis of M. tuberculosis recovered from patients was 11 days (range: 7-13
      days). No significant differences were found regarding contamination of
      respiratory samples in the three systems. CONCLUSION: Given the simplicity of
      utilization of the new system-which does not require radioactive compounds- and
      the results, the MGIT system appears as an easy-to-use new method, which yields
      results in a short time, with a good sensitivity in detecting Mycobacterium
      tuberculosis from clinical specimens from suspected patients with tuberculosis.

PMID- 9273578
TI  - [Tuberculosis outbreak at a public school].
AB  - BACKGROUND: At school there are special circumstances of living together and a
      particular susceptibility, which favour the emergence of tuberculosis
      microepidemics. We report here the microepidemic occurred at a school among 9
      year old children. METHODS: After ruling out a possible familiar source in a
      child with pulmonary tuberculosis, we detected a case with high bacillar shedding
      in a female teacher and conducted a tuberculin search among children and
      teachers, initially outlining the theoretical groups at risk. Tuberculin positive
      children underwent chest-X-ray and when abnormalities were found, children were
      derived to the pediatrician for chemotherapy. All converters received secondary
      chemoprophylaxis and all non-respondents primary chemoprophylaxis. RESULTS: The
      classroom where the teacher spent most of het time had a higher rate of
      converters (70%) than other classroom, where the index teacher spent only a
      partial time (40%; RR: 1.75; CI: 1.06-2.88) or the collective of teachers (45.4%;
      RR: 1.45; CI: 0.94-2.23). Three additional cases of secondary disease were
      detected, all of them children. The initial compliance with chemoprophylaxis was
      greater among (for) children (97.0%) than among teachers (41.6%). Among children
      there was one case of tuberculin conversion compared with three cases among
      teachers. No additional cases were detected; also, an abnormal rate of reactors
      outside the initially studied groups was also not detected. CONCLUSIONS: Our
      results somehow agree with those reported from other school outbreaks. To note
      the anergy and lack of symptoms in the index case and the suggestion to delineate
      the degree of spending hours together to identify groups with a higher
      theoretical risk of being infected. Thus, an unnecessary expense of resources and
      a social alarm would be avoided.

PMID- 9273579
TI  - [Mycobacterium avium complex infection: a growing problem in our country].
AB  - Since the emergence of AIDS, disseminated Mycobacterium avium complex (MAC)
      infection has become a growing cause of morbidity and mortality in this group of
      patients. Our objective was to study the incidence and the clinical and
      microbiological features of MAC infection in HIV-positive patients as well as the
      response to a therapy regimen combining clarithromycin and ethambutol. At our
      hospital, the first patient with disseminated MAC infection was diagnosed in
      1988. Since then, 54 HIV-positive patients with MAC infection have been diagnosed
      (30/1,000 HIV-positive patients). MAC represented 12% of recovered mycobacteria
      in HIV-positive patients and this percentage has increased from 3.9% in 1988 to
      16.4% in 1994. All episodes of MAC infection occurred in patients with advanced
      HIV diseases (mean CD4: 73/microliter). MAC infection was the disease diagnosing
      AIDS in 23.4% of cases. The most common clinical manifestations included fever
      (85.7%), weight loss (55%), and pulmonary involvement (50%). A total of 55
      specimens were processed for mycobacterial culture from 54 patients (mean of 10.2
      specimens per patient). A total of 122 were positive (21.9%: 2.25 positive
      specimens per patient). The specimens with the greater percentage of positive
      results were bone marrow aspirates (65.3%) and blood cultures (47.7%), followed
      by respiratory (16.5%) and urine specimens (5.3%). Regarding therapy, sixteen of
      the 54 investigated patients did not receive specific drugs for MAC infection, 7
      were treated with different combinations of active drugs against MAC (rifampin,
      clofazimine, amikacin, ethambutol, and isoniazid) and 31 received a combination
      of clarythromicin (1 g/12 hourly) and ethambutol (400 mg/12 hourly). Seventy-four
      percent of patients treated with clarythromicin and ethambutol improved
      clinically, and the mean survival time in these patients (253 days) was
      significantly longer than that in not treated patients (p < 0.05). No significant
      differences were noted in survival time between the group of patients treated
      with clarythromicin and ethambutol and that with other drug combinations. The
      incidence of disseminated MAC infection in our environment is increasing in
      patients with advanced HIV disease. The combination of clarythromicin plus
      ethambutol was well tolerated and efficient for the treatment of disseminated MAC
      infection.

PMID- 9273580
TI  - [Predictive factors of non-compliance with anti-tuberculosis treatment in
      patients infected with the human immunodeficiency virus].
AB  - A study was conducted to know the rate of non-compliance of antituberculosis
      therapy among HIV-infected patients, the factors associated with non-compliance
      and the evolution of these patients. The therapy compliance in 276 tuberculous
      HIV infected patients diagnosed in two Madrid hospitals was analyzed. Fifty-one
      patients (18%) were not included in the analysis (6 died without therapy, 6 were
      lost and 39 died during therapy). Out of the 225 evaluable patients, 36 (16%, 95%
      CI, 11.6-21.6) did not comply with therapy. The only factor associated with a
      higher therapy non-compliance was the antecedent of drug use (20% of non
      compliance; relative risk: 10, 95% CI, 1.4-71). Patients using drugs at
      tuberculosis diagnosis had higher risk for non-compliance (31%; RR, 3.1; 95% CI,
      1.6-6.3). The incidence of tuberculosis reactivation after leaving therapy was
      78.8/100 patient-years. Therapy non-compliance increased death risk associated
      with tuberculosis (RR, 9.8; 95% CI, 4.6-21). Programs for controlling
      antituberculous therapy should give priority to active drug users, as this is the
      group with the highest risk for non-compliance.

PMID- 9273581
TI  - [Prevalence of susceptibility to quinolones and other antibiotics in
      microorganisms isolated from community bacteriuria in Madrid in 1995. Study Group
      of Infections in Primary Care].
AB  - BACKGROUND: For the empiric therapy of urinary tract infections (UTI) in the
      extra-hospital setting the susceptibility patterns of potential pathogens, among
      some other factors, should be considered. Thus, the evolution in susceptibility,
      mainly influenced by the previous consume of antibiotic, can be observed when
      comparing with susceptibility patterns in the previous years. MATERIAL AND
      METHODS: All isolates obtained from patients with bacteriuria from 4 Health Areas
      in Madrid for a 3-week period were collected. The susceptibility to 4 quinolones
      and other 9 antibiotics was determined by the agar dilution method. The chi
      square test was used to compare the results obtained with Escherrichia coli
      isolates with those obtained with the same method in 1992. RESULTS: A total of
      945 isolates were recovered. E. coli accounted for 71.4% of isolates; other gram
      negative bacilli for 20.2% and gram-positive cocci for 8.4%. The percentages of
      E. coli isolates susceptible to ampicillin, cotrimoxazole, norfloxacin and
      ciprofloxacin, phosphomycin, cefuroxime, and cefuroxime-axetil were 40.5, 74.7,
      91.6, 97.8, 98.1 and 75.9, respectively. Isolates with cefotaxime MIC higher than
      0.5 mg/l were not detected. Significant differences were observed (p < 0.01) for
      susceptibilities recorded in 1992 and 1995 for amoxycillin/clavulanic acid,
      cefazolin, and the four quinolones. The antibiotics with the best in vitro
      activity against the remaining gram-negative bacilli were norfloxacin and
      ciprofloxacin (98% of susceptible isolates), gentamicin (97%) and cefotaxime
      (95%). CONCLUSIONS: Changes in susceptibility results for E. coli between 1992
      and 1995 have been observed. By 1995, there are commercially available
      antibiotics with good in vitro activity against pathogens with the potential of
      causing extra-hospital UTI in our setting.

PMID- 9273583
TI  - [Clinical meaning of increased alkaline phosphatase].

PMID- 9273582
TI  - [Type I Gaucher's disease. Report of 2 affected families].
AB  - Gaucher's disease (GD) is the most common lisosomic deposit disorders which is
      caused by an inherited deficit of the glucocerebrosidase enzyme. The most common
      for in the adult is type I and the clinical manifestations include liver and
      spleen enlargement, thrombocytopenia, and skeletal changes. Four patients with GD
      type I are here reported. They belonged to two different families and these
      underwent enzyme and genetic investigations. Eight healthy carriers were
      identified and the genetic counsel was given. The most relevant clinical
      manifestations included liver and spleen enlargement (3/4), thrombocytopenia
      (3/4), skeletal changes (2/4) and pulmonary involvement (1/4). Diagnosis was
      achieved by the demonstration of a decrease in the leukocyte enzymatic activity
      in the four patients. The mutation observed most frequently (66%) was N370S. The
      patient with pulmonary involvement has been under substitutive enzyme therapy for
      9 months by means of alglucerase infusions (placental derivative of
      glucocerebrosidase), and an improvement in pulmonary function testing has been
      observed.

PMID- 9273584
TI  - [Urinary tract infection: up-date on concepts with therapy implications].

PMID- 9273585
TI  - [Fever, pleural effusion, and eosinophilia in a 48-year-old immunocompetent
      male].

PMID- 9273586
TI  - [Multiple lung nodules associated with breast nodule].

PMID- 9273588
TI  - [Acute respiratory failure in a 79-year-old male].

PMID- 9273587
TI  - [Young man with progressive constipation and pelvic pain when walking].

PMID- 9273589
TI  - [Painful skin tumors revealing pathology of the female genital system].

PMID- 9273590
TI  - [Emergency treatment of hypertension with lacidipine].

PMID- 9273591
TI  - [Acute recurrent dystonia secondary to neuroleptic suppression].

PMID- 9273592
TI  - [Acute adrenal gland insufficiency and disseminated tuberculosis].

PMID- 9273593
TI  - [Cutaneous lupus with unusual course].

PMID- 9273594
TI  - [Recurrent or episodic fever of unknown origin as the sole symptom of colon
      neoplasm].

PMID- 9273595
TI  - Recent progress in hormone research. Proceedings of the 1996 conference.

PMID- 9273596
TI  - [Hyperhomocysteinemia: risk factor for premature atheromatosis].
AB  - Hyperhomocysteinemia is an independent risk factor for atherosclerosis and
      cardiovascular disease. The cause of hyperhomocysteinemia is either an inborn
      metabolic defect or acquired. Main causes are either a defective homocysteine
      remethylation (thermolability of the enzyme 5,10-methylenetetrahydrofolate
      reductase) or nutritional deficiencies of B vitamins especially folic acid. The
      relative risk for myocardial infarction has been found of 3,1 in case of
      hyperhomocysteinemia. It is considered that a 5 microM/l homocysteine increment
      elevates vascular risk by as much as cholesterol increases of 20 mg/dl. B
      vitamins supplements are potentially useful.

PMID- 9273597
TI  - [Antiphospholipid antibodies, lupus anticoagulant and thrombosis].
AB  - Antiphospholipid antibodies are associated with venous and arterial
      thromboembolism and with fetal loss. These associations are found either in
      autoimmune disease or without any other associated disease. In the first case one
      will speak of secondary antiphospholipid syndrome and in the second of primary
      antiphospholipid syndrome. The detection techniques of these antibodies have been
      improved these last years, although they remain difficult to standardize. The
      treatment of thromboembolism is based on the use of heparin and oral
      anticoagulants. Several therapeutic options exist to treat fetal losses, among
      which corticosteroids, subcutaneous heparin and aspirin are the most frequently
      used.

PMID- 9273598
TI  - [The appropriate use of clinical biological tests in hypercoagulability].
AB  - Biological markers who are associated with hypercoagulability are of two types:
      Markers of activation: among them, the most interesting are the D-dimers which
      are good tools of diagnostic for the deep venous thrombosis and the pulmonary
      embolism. Thanks to their high negative predictive value. Etiological factors of
      hypercoagulable states and thrombosis, in other words: the "hypercoagulability
      chek up". This one should never be systematic. We propose either to practice it
      one month after the end of the anticoagulant therapy or to make it with
      prophylactic doses of low molecular weight heparin and far from the thrombotic
      episode.

PMID- 9273599
TI  - [Preventive management of patients presenting with an increased tendency to
      venous thrombosis].
AB  - The thrombophilias are conditions characterized by an increased tendency to
      thrombosis. This paper aims at presenting the actual guidelines concerning the
      preventive attitudes in the thrombophilias that mainly expose to venous
      thromboembolism. The identification of these thrombophilias resides on one hand
      on the patients' and their family's history of venous thrombosis, and on the
      other hand on the diagnosis of disorders known to be associated with an increased
      risk of venous thrombosis. Heparin-associated thrombocytopenia of type II is a
      still too often underdiagnosed syndrome in which the prevention of thrombosis
      requires a specific approach. The authors discuss thoroughly the preventive
      attitudes for patients that do not require a long-term anticoagulation, for
      patients in whom a long-term anticoagulation is generally recommended, and for
      patients in whom it is sometimes recommended. The practical use of
      anticoagulation is described. Lastly, a special attention is paid to situations
      in which the thrombotic risk is increased, such as prolonged immobilization,
      surgery, traumas, pregnancy and postpartum, contraception and oestrogen therapy.

PMID- 9273600
TI  - [Accelerated desensitization for hymenoptera venom allergy in 30 hours: efficacy
      and safety in 150 cases].
AB  - In this study, we performed 150 desensitizations in 139 Hymenoptera venom
      allergic patients (109 Yellow jacket allergic patients, 19 Honey bee allergic
      patients and 11 patients sensitized to both insects, who received a dual
      desensitization). We used a rush protocol, allowing injection of a total
      cumulated dose of 125,1 (Honey bee) to 175,1 (Yellow jacket) microgram of venom
      in 30 hours. Patients were hospitalized, with all emergency precautions for
      treating systemic reactions. The protocol was well tolerated in 147/150 cases; 3
      patients had a benign systemic reaction. Patients received monthly maintenance
      doses of 100 micrograms venom. 39 patients experienced a field sting during
      immunotherapy; 2 of them (5%) had a benign systemic reaction. Thus, our rush
      desensitization protocol seems to be safe and effective.

PMID- 9273601
TI  - [Anatomo-clinical conference: lymphoma and mediastinal mass].

PMID- 9273602
TI  - [Hypercoagulable states: definition and general mechanisms].
AB  - Hypercoagulable states are characterized by an increased risk for developing
      venous and arterial thrombosis. This situation is the consequence of inbalance of
      the hemostatic activity (fibroinformation > fibrinolysis). Primary and secondary
      hypercoagulable states are reviewed and clinical situations mandatory for a
      laboratory evaluation are discussed.

PMID- 9273603
TI  - [Factor V Leiden and activated protein C resistance].
AB  - Factor V Leiden is characterised by a point mutation which prevents the
      physiologic inhibition of activated factor V by activated protein C (Activated
      Protein C Resistance). This mutation is now considered as the most frequent
      inherited thrombophilic disorder. It is found in about 20% of patients with
      venous thrombotic disease, far before ATIII, Protein C and S deficiency. Its
      prevalence (4% in the general belgian population, 1 to 15% in Europa) allows
      frequent associations with other thrombophilic disorders, inherited or acquired,
      such as contraceptive pill. Biological testing are now ready for screening, but
      the opportunity of a systematic evaluation in front of a risk situation remains a
      matter to discussion.

PMID- 9273604
TI  - [Aging of the population: demographics for the Liege region].

PMID- 9273605
TI  - [Biological mechanisms of aging].

PMID- 9273606
TI  - [Variations in reference biological parameters with age].

PMID- 9273607
TI  - [Particulars about pharmacotherapy in the elderly patient].

PMID- 9273608
TI  - [Diabetes in the elderly patient].

PMID- 9273609
TI  - [Is the hypothalamohypophyseal control system modified during human aging?].

PMID- 9273610
TI  - [Dehydration in the elderly patient].

PMID- 9273612
TI  - [Cardiovascular impact of postmenopausal hormone therapy: new data].

PMID- 9273611
TI  - [Andrological data on male sexuality in the elderly].

PMID- 9273613
TI  - [Comparative analysis of indications and results of percutaneous coronary
      angioplasties according to age].

PMID- 9273614
TI  - [Carotid surgery beyond 75 years old].

PMID- 9273615
TI  - [Pulmonary problems related to aging].

PMID- 9273616
TI  - [Anal incontinence (in the elderly)].

PMID- 9273617
TI  - [Diagnostic, therapeutic and socioeconomic problems in geriatric oncology].

PMID- 9273618
TI  - [Alzheimer's disease].

PMID- 9273619
TI  - [Depression in the elderly].

PMID- 9273620
TI  - [How I treat...senile osteoporosis].

PMID- 9273621
TI  - [Bone and joint manifestations in the elderly patient].

PMID- 9273622
TI  - [Total hip replacement in the elderly patient: indications and results].

PMID- 9273624
TI  - [Frequent skin tumors in geriatrics].

PMID- 9273623
TI  - [From cellular senescence to seven ways of skin aging].

PMID- 9273625
TI  - [Therapeutic alternatives to systemic corticotherapy in severe and chronic
      dermatologic disorders in the elderly patient].

PMID- 9273626
TI  - [Cataracts due to age].

PMID- 9273627
TI  - [Presbycusis].

PMID- 9273628
TI  - [Pharma-Clinics. The drug of the month. Meloxicam (Mobic)].

PMID- 9273629
TI  - [Image of the month. Immediate vasovagal syncope].

PMID- 9273630
TI  - [How I treat...a patient at risk of infectious endocarditis].

PMID- 9273631
TI  - [Clinical case of the month. Association of renal polycystosis and an aneurysm of
      the middle cerebral artery].

PMID- 9273632
TI  - [Recognizing the signs of child abuse on the skin].

PMID- 9273633
TI  - [Vasovagal syncope].

PMID- 9273634
TI  - [Inhibitors of platelet receptors GP IIB/IIIA: a new therapeutic class and its
      promise in the treatment of acute coronary syndromes].

PMID- 9273635
TI  - [Therapeutic monitoring of antidepressants].

PMID- 9273636
TI  - [The practice of placing under psychiatric observation].

PMID- 9273638
TI  - [Foot drop. A differential diagnosis problem].

PMID- 9273637
TI  - [Helicobacter pylori and MALT gastric lymphomas].

PMID- 9273639
TI  - [How I investigate... a patient newly diagnosed with/or at risk of diabetes type
      1].

PMID- 9273640
TI  - The medicine of the month. Losartan (Cozaar).

PMID- 9273641
TI  - [Ambulatory anesthesia: towards what future?].

PMID- 9273642
TI  - [Specificity of the anesthetic consultation for ambulatory surgery].

PMID- 9273643
TI  - [Intravenous anesthetic agents in ambulatory anesthesia].

PMID- 9273644
TI  - [Local and regional anesthesia for ambulatory surgery].

PMID- 9273645
TI  - [Volatile agents in ambulatory anesthesia].

PMID- 9273646
TI  - [Toxicity of local anesthetics].

PMID- 9273647
TI  - [Evaluation of fifteen months' activity in an ambulatory surgery center in a
      university hospital].

PMID- 9273648
TI  - [Sociability, violence and exclusion].

PMID- 9273649
TI  - [Awakening, sleep and length of sleep in children].

PMID- 9273650
TI  - [Sensitivity training for debriefing in the school context].

PMID- 9273651
TI  - [In times of survival, the right of silence].

PMID- 9273652
TI  - [Psychiatric care of neglected and abused children and their parents].

PMID- 9273653
TI  - [Visual acuity screening tests during the school years: how often and which
      threshold to chose?].

PMID- 9273654
TI  - [Role of education in the patient with chronic diseases: example of asthma and
      chronic obstructive lung disease].

PMID- 9273655
TI  - [Under the sign of change (speech on the occasion of the opening of classes].

PMID- 9273656
TI  - [The practice of resuscitation or daily physiopathology].

PMID- 9273658
TI  - [Report from the educational symposium on prophylaxis of civilization related
      diseases from food--nutrition--drugs].

PMID- 9273657
TI  - [Proliferation of peroxisomes and the hepatocarcinogenic process].
AB  - Peroxisome proliferators are diverse group of chemicals which are regarded as
      rodent hepatocarcinogens and/or- liver tumor promoters. These compounds when
      administered to rats and mice produce a dramatic increase in the size and number
      of hepatic peroxisomes and increase in activities of enzymes involved in beta
      oxidation of fatty acids. Peroxisome proliferation is accompanied by hepatocyte
      proliferation and liver growth. The steroid hormone receptors superfamily have
      been identified that can be activated by peroxisome proliferators and are called
      Peroxisome Proliferator Activated Receptors (PPARs). It is therefore suggests
      that PPARs mediate the pleiotropic effects of peroxisome proliferators including
      enzyme induction, peroxisome proliferation, cell proliferation and
      hepatocarcinogenesis. Although the correlation of peroxisome proliferation and
      hepatocarcinogenesis is striking, the mechanism(s) by which this class of
      chemicals induce tumor is still understood; however several other hypothesis have
      been advanced. One is based on knowledge that hydrogen peroxide is produced
      during the increase in peroxisomal fatty acid oxidation. An excess of hydrogen
      peroxide can lead to oxidative stress (generation of reactive oxyden species),
      DNA damage and possibly to tumor initiation. In rodents, an alternative mechanism
      is the promotion of spontaneously initiated lesions by sustained cell
      proliferation. Thirdly, it is conceivable that sustained growth stimulation may
      be sufficient for tumor formation. Marked species differences are apparent in
      response to peroxisome proliferators. Rats an mice are extremely responsive
      species, and hamsters show an intermediate response, while guinea pigs, monkeys
      and humans appear to be relatively non-responsive. In the light of these data it
      seems likely that risk to humans from peroxisome proliferators may be
      overestimated. However, peroxiome proliferators have shown to produce the other
      effects such as the suppression of hepatocyte apoptosis which could be an
      important factor in their hepatocarcinogenic response.

PMID- 9273659
TI  - [Organ cytotoxicity of selected polycyclic aromatic hydrocarbons in mice].
AB  - The cytotoxic effects of some PAHs: DMBA, 3-MC and B(a)P on the lymphatic organs,
      liver and kidney of mice have been investigated. These PAHs in doses of 100 mg/kg
      were dissolved in 0.5 ml 20% DMSO and were given intraperitoneally in female mice
      Balb/c. After 7 days, organs weight, cellularity in lymphoid organs and tissue
      structure of liver and kidney were analyzed. The greatest effect of DMBA was
      observed on cellularity of spleen. 3-MC and B(a)P caused significant hepatotoxic
      and nephrotoxic changes. 3-MC induced focal destruction of hepatocytes and
      sometimes--irregular mitotic figures (c-mitosis). After B(a)P administration in
      liver cells were mainly observed the changes in distribution of interphase
      nucleolar organizer region (AgNOR). In kidney--irregular glomeruli and tubuli
      after 3-MC and B(a)P were noted. The above results may indicate that the
      cytotoxic effects of PAHs depend on the type of compound administered.

PMID- 9273660
TI  - [Evaluation of the combined effect of lead and sodium nitrite on some blood
      biochemical parameters in blood of rats during subchronic exposure. Influence on
      levels of methemoglobin, sulfhydryl groups and tryptophan].
AB  - The study was performed on 4 groups of male Wistar rats, receiving p.o. through 3
      months every day: 1) distilled. water (control group); 2) sodium nitrite in dose
      30 mg/kg b.w. x day (20% LD50); 3) lead acetate in dose 10 mg/kg b.w. x day (6.7%
      LD50); 4) lead acetate and sodium nitrite in amounts as above. The methemoglobin
      and hemoglobin were determined in whole blood, tryptophan--in plasma and free
      sulfhydryl groups--in erythrocytes. There was shown methemoglobin creative
      effects by nitrite (4.17%) and lead (3.02%) after 90-days intoxication. Both
      nitrite and lead significantly decrease free sulfhydryl groups and tryptophan
      levels in blood. There was also observed that lead administrated together with
      sodium nitrite does not increase methemoglobin concentration.

PMID- 9273661
TI  - [Mutagenic activity of atmospheric dust in Warsaw].
AB  - The results are presented of the studies of the mutagenic activity of dust
      samples in atmospheric air in Warsaw in the heating and non-heating seasons. Dust
      samples were obtained with a Staplex-type device continuously during 24 hours.
      The dust collected on the filters was extracted with cyclohexane. The devaporized
      and dried extract, that is the so called tar substances, were the material for
      further studies. The mutagenic activity of the studied samples was determined
      using a modification of the test of somatic mutation and recombination (SMART) on
      Drosophila melanogaster. The cross-bred strain mwh x ORR: flr3/TM3, Ser specially
      prepared for the research of WAA was used. The dust in atmospheric air of Warsaw
      showed mutagenic activity which was higher in samples taken in the heating
      season.

PMID- 9273662
TI  - [The assessment of population exposure to atmospheric air pollution].
AB  - The air pollution concentrations of SO2 and suspended particulate matter in 1993
      in one Polish city Poznan and over entire Poland have been modeled and mapped.
      The data for Poznan were obtained during special epidemiological study by means
      of a dense network of passive samples and the data for Poland were obtained from
      the routine network operated by Sanitary Epidemiological Stations. The modeling
      employed the kriging method of ARC/INFO computer package. It was found that about
      1/3 of Polish population was exposed to the SO2 and/or SPM level that exceeded
      annual recommended values. In Poznan 25% of children aged 8-9 years were exposed
      to SO2 level above 100 during heating season 1992/1993.

PMID- 9273663
TI  - [Exposure of inhabitants of Poznan to fluorides. I. Fluorides in atmospheric air,
      tap water and selected additional fluids].
AB  - The purpose of the study was to obtain information about fluoride pollution of
      the human environment. Fluoride concentrations were measured in atmospheric air,
      water and certain drinks. The measurements were done with a ion-selective
      electrode. In the atmospheric air of Poznan and its environs the concentrations
      ranged from 0.0006 mg/m3 to 0.0122 mg/m3. Tap water in Poznan contained 0.2 mg
      F3/dm3, on average. The selected drinks--mineral water and tea contained 0.3 and
      1.5 mg F-/dm3 respectively. The acceptable values of fluoride concentrations were
      not exceeded, but fluoride concentration in atmospheric air was higher than that
      found usually in other regions of the country. In drinking water fluoride
      concentration in Murowana Goslina was within the acceptable range, and in Poznan
      it was twice lower.

PMID- 9273664
TI  - [Exposure of Poznan inhabitants to fluorides. II. Fluorides in urine and hair of
      school children].
AB  - In view of the plans of fresh water fluoridation in Poznan the necessity arose of
      obtaining of information about the exposure to fluoride compounds. The reported
      study was carried out in Poznan and environs. Urine and hair samples of children
      were obtained. The determinations were done with a ion- selective electrode. The
      mean fluoride concentrations in urine were between 0.3 and 0.9 mg F-/dm3. The
      concentration in hair was 2.2 mg F-/g in Poznan and 3.3 mg F-/g in Lubon. These
      values were, however, not exceeding the acceptable ones. In Lubon the
      concentrations of fluorides in hair was 50% higher than in Poznan. The authors
      believe that the possible cause was Fertilizer Chemical Works in that location.

PMID- 9273665
TI  - [The prevalence of bacterial and fungal aerosol in homes, offices and ambient air
      of Upper Silesia. Preliminary results].
AB  - Quantitative criteria of microbiological air quality in homes and offices are
      needed for practical reasons. The purpose of this study was to obtain the
      preliminary characteristic of bacterial and fungal aerosols in healthy buildings.
      It was analysed the concentrations levels and size distributions of the
      investigated bioaerosols. The obtained data can be treated as a first step in the
      direction of determining so called normal level for different bioaerosols in
      homes and offices in Poland. The concentrations of airborne bacteria and fungi
      were measured using 6-stage Andersen impactor. The Trypcase Soy Agar were applied
      for bacteria and 2% Malt Extract Agar for fungi. The bacteria samples were
      incubated for 2 days at 37 degrees C and the fungi samples respectively for 4
      days at 25 degrees C. The indoor levels of bacterial aerosol (homes: 212-888
      cfu/m3, offices: 136-542 cfu/m3) were higher than the outdoor levels
      (respectively: 42-386 cfu/m3 and 13-115 cfu/m3). The fungal aerosol
      concentrations were lower indoors (homes: 81-383 cfu/m3, offices: 18-133 cfu/m3)
      than outdoors (94-625 cfu/m3). There were distinctly higher concentrations of the
      investigated bioaerosols in homes than in offices. The aerodynamic diameter of
      most bacterial particles were higher than 7 microns, both in indoor air (homes:
      57-260 cfu/m3, offices 19-118 cfu/m3) and outdoor air (respectively: 9-145 cfu/m3
      and 0-71 cfu/m3). The maximum for fungal spore levels were observed in the size
      range 3.3-4.7 and 2.1-3.3 microns in the instance of homes (respectively: 12-155
      cfu/m3 and 19-154 cfu/m3) and in the size range 2.1-3.3 microns in the instance
      of offices (6-55 cfu/m3). Largest numbers of this bioaerosol in outdoor air were
      isolated in the size range 2.1-3.3 microns (25-208 cfu/m3). Although there are
      some proposals for an upper limit of the normal indoor concentration of airborne
      bacteria and fungi, but due to different climate and housing conditions we can
      expect other normal range of fungal and bacterial aerosol in Polish homes.

PMID- 9273666
TI  - [The content of radon 222Rn in deep borehole water of the Pojezierze Mazurskie
      terrain].
AB  - Radon 222Rn in deep borehole water of Pojezierze Mazurskie region has been
      quantitative determined. The measurement were performed using the alpha liquid
      scintillation counting method. The water samples were examined from three
      voivodships: Elblag, Olsztyn and Suwalki. In some cases the concentrations of
      222Rn in investigated water samples exceed 11 Bq/l.

PMID- 9273667
TI  - [Compounds from the chlordane group in adipose tissue of harbour seals from the
      Gulf of Gdansk].
AB  - The composition and the concentration of chlordanes were shown in blubber of
      harbour porpoises collected from the Gulf of Gdansk, Baltic Sea, in 1991-1992.
      Chlordanes were determined using capillary gas chromatography and low resolution
      mass spectrometry (HRGC/LRMS). The range of CHLs concentration in blubber was
      between 420-1000 ng/g wet weight (470-1300 ng/g lipid weight). The composition of
      CHLs residues was similar in males and females, with trans-nonachlor (37%) as a
      most abundant compound, and followed by heptachlor epoxide (15%), cis-chlordane
      (14%), cis-nonachlor (14%), oxychlordane (11%), MC6 (3%), MC5 (2%), trans
      chlordane, MC7, U82 and MC4 (< 1%).

PMID- 9273668
TI  - [Methods of nutrient intake and nutritional status of the elderly in Poland on
      the basis of the literature from the years 1980-1996].
AB  - According to papers published in the years 1980-1996 there were many faults in
      nutritional habits of the elderly in Poland, which can affect nutritional and
      health status. Low consumption of calcium, vitamins C, A, and B group was
      identified most often while the intake of fats was too high in comparison to
      Polish recommended daily intake. Moreover iron and protein intake among women
      were also too low. The analysis of food products intake indicated that above
      mentioned inadequacy in nutrient intake was the result of low consumption of milk
      and milk products, fruits and vegetables containing vitamin C and beta- carotene
      as well as grain products and potatoes and high consumption of products from the
      group other fats. The observed differences between intake and nutritional
      recommendation were confirmed by the indices of nutritional status. BMI
      indicating overweight or obesity was observed for many subjects under study, more
      frequently among women than among man. Biochemical analysis showed risk of
      deficiency of some vitamins.

PMID- 9273669
TI  - [Wegener's granulomatosis. Apropos of a case].
AB  - A rare case of granulomatosis of Wegener is rapported in this study. One patient
      presented with ENT and pulmonary symptoms. The differential diagnosis with
      tuberculosis was raised. Based on a literature review, the authors discuss
      clinical, pathological and imaging features of the condition and its management.

PMID- 9273670
TI  - [Anesthesia with the laryngeal mask during the treatment of fractures of the
      nose. A study of a group of 53 patients].
AB  - General anesthesia was obtained using a laryngeal mask in 53 patients with nasal
      fractures. The advantages of this procedure are: no need for curarization, easy
      removal, and awakening in the operating room. No complications were observed
      although orotracheal intubation was necessary in 3 patients.

PMID- 9273671
TI  - [The surgical management of obstructive sleep apnea syndromes. Preliminary phase
      I results (the Stanford technic) in a series of 26 patients].
AB  - Surgical management of obstructive sleep apnea remains a surgical challenge.
      Multidisciplinary collaboration is a fundamental element. We report the
      principles of management as proposed to the patient and preliminary results
      obtained in a series of 26 patients treated in the phase I of the Stanford
      protocol. Cure rate after this phase was 50%. Different research projects in this
      area are discussed.

PMID- 9273672
TI  - [Chondrosarcoma of the temporomandibular joint. Apropos of a case and review of
      the literature].
AB  - Chondrosarcomas of the temporo-mandibular joint are exceptional and have been
      previously reported in the literature in only seven cases. A case located in the
      temporal bone with extension in the infratemporal fossa and the cranial base is
      presented. Treatment consisted in a wide surgical resection combined with
      postoperative radiotherapy. The patient is alive with a follow-up of more than
      two years.

PMID- 9273673
TI  - [Iatrogenic cervicofacial hydatid cysts. Apropos of a case].
AB  - The writers give an account of a cervicofacial hydatid dissemination case,
      provoked by iterative ponctions of hydatid cyst initially isolated in the left
      maxillary sinus. They state diagnostic and therapeutic difficulties sometimes
      found and they insist on the role that must be played by immunologic tests in
      diagnostic approach and treatment monitoring of this disease which is
      unfortunately current and serious.

PMID- 9273674
TI  - [Histiocytosis X with mandibular involvement. Apropos of a case].
AB  - This is a case report of mandibular Histiocytosis X in its Eosinophilic
      Granuloma's form. A review of literature is realized in the two clinical forms of
      Histiocytosis X: localised forms, with insistance in the Eosinophilic Granuloma
      of jaws, and diffused forms represented by the Letterer-Siwe disease and the Hand
      Schuller-Christian disease.

PMID- 9273675
TI  - [Facial pain].
AB  - Whether acute, chronic or recurrent, facial pain remains an therapeutic
      challenge. Neurological tests, otorhinolaryngologic, dental or psychiatric
      examinations do not always provide a precise diagnosis. We propose a review of
      painful diseases most often found in the head and neck region. A differential
      diagnosis between psychiatric and functional diseases is proposed although the
      subjective component is always present. Neuralgias, migraine, cluster headache,
      tension-type headache, atypical facial pain and cancer pain are reviewed.

PMID- 9273676
TI  - [Mandibular mechanics in temporomandibular joint pain-dysfunction syndrome].
AB  - There are several reasons for perturbed mandibular mechanics in SADAM:
      craniofacial architecture anomalies, malocclusions, lingual dyspraxia, postural
      disorders. SADAM diagnosis and therapeutics should be conducted by a
      pluridisciplinary team.

PMID- 9273677
TI  - [Ultrasonographic study of the craniomandibular joint. Evaluation of the technic:
      apropos of 140 examinations].
AB  - Ultrasonography of the temporomandibular joint is a non-invasive, low cost, easy
      to perform examination. Despite promising results, further improvements in
      reliability can be expected with technological progress. We report our experience
      with 140 explorations which we hope incite interest of other researchers in this
      technique.

PMID- 9273678
TI  - [Critical review of the various treatments of temporomandibular joint pain
      dysfunction syndrome. What will be the psychosomatic approach to these
      patients?].
AB  - A multitude of theoretical, etiologic and therapeutic approaches to
      temporomandibular joint (TMJ) dysfunction have been developed. In spite of all
      the efforts for combined therapy that have proliferated over the last years, the
      therapeutic options proposed for these patients are extraordinarily diversified
      and vary with the different schools. The different opinions are rarely in
      agreement. Everyone appears to be satisfied with such an extremely divergent
      approach to treatment where some patients undergo surgery of the TMJ while
      relaxation is proposed for others! In view of these very diverging opinions, we
      raise the question as to whether the results obtained with a truly psychosomatic
      approach using well-coordinated team work between stomatologists and
      psychotherapists might have a theoretical basis.

PMID- 9273679
TI  - [Patient-controlled exercise therapy in temporomandibular joint pain-dysfunction
      syndrome].
AB  - Self-controlled gymnastics in SADAM relaxes the masticator muscles, allows
      precise assessment of occlusion and helps the patient acquire occlusion
      conscience. The technique is entirely patient controlled.

PMID- 9273681
TI  - [Primary teratoma of the orbit. Apropos of a case].
AB  - Primary teratomas rarely occur in the orbit leading to major exophthalmia in the
      neonate. We report a case in a female infant who presented globular right
      exophthalmia extending beyond the orbit caused by a teratoma of the orbit. There
      was right ophthalmoplegia. Computed tomography showed enlargement of the orbit
      without modification of the bony structure despite the tumor volume. Tumoral
      enucleation was performed via the transconjunctive route. Histology reported
      benign mature multi-tissue teratoma. The postoperative course was uneventful. The
      CT-scan at 6 months evidence the absence of recurrence, outcome which has been
      confirmed after a 5-years follow-up.

PMID- 9273680
TI  - [Intravenous sedation in implantology].
AB  - Local or block anesthesia can be used satisfactorily in many implant procedures.
      However, when advanced implant techniques or pre-prosthetic reconstruction
      surgery of the maxillofacial bones are required, local or regional anesthesia is
      insufficient. The "day-hospital" concept is a rational approach which meets the
      requirements for anesthesia and deep sedation with criteria for patient safety
      and comfort while guaranteeing optimal operating conditions. Intravenous
      sedation, both "conscious" and "deep" sedation, is a very well adapted form of
      anesthesia for implant recipients. Local or block anesthesia is enhanced or
      reinforced prior to surgery by the intravenous administration of a sedative and
      anxiolytic agent (single-drug concept), such as a benzodiazepine, associated or
      not with a morphinomimetic agent and an antihistaminic substance (multiple-drug
      concept). The main goal is to maintain spontaneous respiration while obtaining
      postoperative amnesia of the entire procedure. Mandatory use of a pulse oximeter
      has greatly contributed to improved safety of intravenous sedation, essentially
      indicated for operations not lasting more than 2 and a half hours in patients in
      good general health (scoring 1 or 2 in the American Society of Anesthesiology
      (ASA) classification) and with a low risk of postoperative complications. This
      concept requires an adapted technical facility. The operating theatre should have
      all the equipment necessary for cardiovascular, neurological and respiratory
      emergency care. The postoperative recovery room should also be equipped with
      cardiovascular monitoring devices and be able to accommodate an intensive care
      unit. Under these strict rules, short duration surgical procedures (< 150') can
      be performed : 1) with the best conditions of medical safety, 2) with improved
      operating conditions for the implant surgeon (the patient responds immediately to
      vocal orders when necessary) while asepsis is maintained as easily as with
      general anesthesia, 3) with better conditions for postoperative care and patient
      comfort (the anesthetist is continuously present). 4) better psychological
      conditions for the patient who will be discharged the same day, 5) with total
      amnesia of the entire surgical procedure, 6) elimination of a usually
      disproportionately long hospitalization. Day hospitalization also helps contain
      health care costs by cutting out the need for overnight care and accommodation.
      We underline the safety of current intravenous sedation techniques and present
      two series of data related to the use of this technique by an anesthetist and an
      operating surgeon in a day hospital from 1986 to 1995.

PMID- 9273682
TI  - [Professional education: the foundation and the continuation].

PMID- 9273683
TI  - [The clinical significance of temporomandibular joint sounds. A questionnaire
      study among dentists and orthodontists].

PMID- 9273684
TI  - [Physician-patient: a relationship at risk? The work of God and the part of the
      Devil].

PMID- 9273685
TI  - [The structure of morality].

PMID- 9273686
TI  - [Dental surgery and radiology. The St. Moritz Dental Continuing Education Course
      of 6 to 12 October 1996 in Flims].

PMID- 9273687
TI  - [Decision strategies in prosthodontic treatment. The 17th Annual Meeting of the
      Dental Prosthetics Society of Switzerland (ZPGS) on 6 September 1996 in Genf].

PMID- 9273688
TI  - [Microscopes in endodontics. The Endodontology Symposium of 7-8 June 1996 in
      Amsterdam].

PMID- 9273689
TI  - [Will Switzerland soon experience a scarcity of dentists?].

PMID- 9273690
TI  - [Alternatives to amalgam: taking the biophysical factors into consideration in
      the choice of restoration material. The annual congress of the Academy of Dental
      Materials (ADM) of 30 October to 2 November 1996 at Munich].

PMID- 9273691
TI  - A cold for cancer.

PMID- 9273692
TI  - Marijuana addiction.

PMID- 9273693
TI  - Marijuana addiction.

PMID- 9273694
TI  - NIH nixes appeal to bypass patent law.

PMID- 9273695
TI  - Congress readies injection of funds.

PMID- 9273696
TI  - Your complete Web guide to tumors.

PMID- 9273697
TI  - What makes fruit flies roam?

PMID- 9273698
TI  - How TRAIL kills cancer cells, but not normal cells.

PMID- 9273699
TI  - Subtle, secret female chimpanzees.

PMID- 9273700
TI  - The polio eradication effort: should vaccine eradication be next?

PMID- 9273701
TI  - Ending polio immunization.

PMID- 9273702
TI  - Basal forebrain neuronal loss in mice lacking neurotrophin receptor p75.

PMID- 9273703
TI  - Measuring memory in a mouse model of Alzheimer's disease.

PMID- 9273704
TI  - Cytoskeletal regulation of membrane function. Proceedings of the 50th annual
      symposium of the Society of General Physiologists. Woods Hole, Massachusetts, 5-7
      September 1996.

PMID- 9273705
TI  - [Cystic echinococcosis of the hip].

PMID- 9273706
TI  - [Magnetic resonance tomography in early diagnosis of rheumatoid arthritis].

PMID- 9273707
TI  - [Radiologic manifestation of rheumatoid arthritis].

PMID- 9273708
TI  - [Clinical aspects and therapy of degenerative joint diseases].

PMID- 9273709
TI  - [Principles of radio-synoviorthesis].

PMID- 9273710
TI  - [Avascular bone necrosis].

PMID- 9273711
TI  - [Periarticular fractures--what should be observed?].

PMID- 9273712
TI  - [Periarticular fractures of the upper and lower extremity. I: ABC classification
      using the AO principle].

PMID- 9273713
TI  - [Periarticular fractures of the upper and lower extremity. II: Therapeutic
      principle].

PMID- 9273714
TI  - [Fibrous dysplasia].

PMID- 9273715
TI  - Cash benefits for short-term sickness, 1970-94.
AB  - This note has reviewed the extent of protection of workers against income loss
      during the first 6 months of illness or injury. National income loss in 1994 was
      $81.1 billion, of which $49.4 billion (60.9 percent) was replaced by income
      protection programs, including sick leave, group insurance, temporary disability
      insurance under statutory State provisions, individual insurance, workers'
      compensation, and (during the 6th month) the Social Security Disability Insurance
      program. In 1994, wage and salary workers in the private sector lost $55.2
      billion because of nonoccupational illnesses or injuries, of which $19.0 billion
      (34.5 percent) was replaced. Wage replacement rates are higher for full-time
      professional and technical employees with longevity in large or medium firms, and
      especially public employees. The lowest level of coverage is given to part-time
      employees with limited seniority who work in production and related areas in
      small, private firms. Approximately 70 percent of wage and salary workers in the
      private sector have some protection through their employment against earnings
      losses caused by short-term illness. Forty-four percent of these workers have
      short-term disability insurance,and only half have sick-leave coverage.

PMID- 9273716
TI  - Private social welfare expenditures, 1972-94.

PMID- 9273717
TI  - [Use of a turbidometric method for rapid diagnosis of coagulation and clotting
      disorders in patients with acute myocardial infarction].
AB  - In 20 patients with acute myocardial infarction the parameters of coagulation and
      fibrinolysis were evaluated. A high degree of the correlation between the routine
      and turbidimetric methods was found. Turbidimetric express-micromethod may be
      widely used for monitoring coagulation and fibrinolysis parameters in patients
      with acute myocardial infarction.

PMID- 9273718
TI  - [Method of quantitative analysis of phosphorus and stabilizing its content in
      biological and chemical assays].

PMID- 9273719
TI  - [Effect of a binuclear rhenium complex on the conductivity of lipid bilayer
      membranes for alkali metal ions].
AB  - Conductivity of bilayered lipid membrane (BLM) for the ions of alkali metals
      under action of binuclear rhenium complex (V) [Re2(Ph3P)2 (AHK)2O3Cl4] has been
      analyzed. It is found that BLM conductivity sharply increases in presence of
      lithium ions, then it drops and slowly increases again up to maximum value which
      is not changed. If sodium, rubidium and caesium chlorides are used as
      electrolytes the BLM conductivity almost does not change. The mechanisms of
      change of BLM conductivity is suggested for the ions of alkali metals under
      interaction with binuclear complex of rhenium.

PMID- 9273720
TI  - [Study of interactions of methemoglobin with liposomes using the fluorescent
      probe DSM and its derivatives].
AB  - Using fluorescent probes DSM, DSP-6 and DSP-12 interaction of methemoglobin with
      liposomes composed of phosphatidylcholine and diphosphatidylglycerol has been
      investigated. It was supposed that the observed decrease of probes fluorescence
      intensity is determined to some extent by lipids peroxidation.

PMID- 9273722
TI  - [Pyruvate decarboxylase: mechanistic model of paracatalytic interactions].
AB  - The recent data from literature concerning mechanisms of nonenzymic and enzymic
      thiamine diphosphate-dependent catalysis have been analyzed. The application of
      model nonenzymic quinone, molecular oxygen and ferricyanide oxidation of 2-(l
      hydroxyethyl)- and 2-(l-hydroxybenzyl)thiazole ions to catalysis by thiamin
      diphosphate-dependent enzymes especially pyruvate decarboxylase are summarized in
      this review. Mechanisms of paracatalytic interactions of pyruvate decarboxylase
      and possibility of biocatalyst design to change reaction specificity of the
      enzyme have been discussed.

PMID- 9273721
TI  - [Intensity of lipid peroxidation processes and activity of antioxidant enzymes in
      erythrocytes during anemia in pregnancy].
AB  - The given report deals with investigation of the level of spontaneous lipid
      peroxidation (LPO) (as judged by the accumulation of MDA) and activity of
      antioxidative enzymes (GSH-peroxidase, GSH-reductase) in red blood cells of
      pregnant women (24-26 weeks) suffering from minor (blood Hb is 95 g/l) and medium
      (blood Hb is 85-90 g/l) anemias. We have found that as the anemia becomes deeper,
      the red blood cells of pregnant women demonstrate a linear increase in the level
      of spontaneous LPO, which rises by 54% during anemia of moderate severity (p <
      0.02) as compared with control. At the same time, simultaneously with LPO, the
      activity of the above glutathione-containing enzymes increases as the anemia
      progresses, which, apparently, is of the compensatory nature, aimed at the
      maintenance of the reduced glutathione pool, the latter being an important
      component of the cell antioxidative system during LPO activation. The authors
      think the increased activity of the physiological antioxidative system and
      intensification of the LPO processes to be a natural adaptive process, since
      lipid hydroperoxides are the activators of synthesis of prostaglandins, which are
      required in delivery.

PMID- 9273723
TI  - [Membrane proteins as regulators of the complement system].
AB  - The data on structure, biochemical properties and functions of membrane proteins,
      performing cell defence against complement lysis, are summarized. Proteins DAE
      (decay accelerating factor) and CR1 (complement receptor of type 1) reduce the
      stability of complement convertases and cause their dissociation. MCP (membrane
      cofactor protein) and CR1 act as cofactors. In factor I mediated proteolysis of
      the convertase fragments C3b and C4b. The proteins C8bp-(C8-binding protein) and
      protectin affect membrane attack complex assembly. In contrast to MCP and CR1,
      which are integrative proteins, DAF, C8bp and protectin are bound to membranes
      with their glycophospholypid anchors. Tissue distribution of the proteins and the
      ways of their solubilization into biological fluids are reviewed.

PMID- 9273724
TI  - [Role of S-100 protein in the function of brain cell nuclei].
AB  - Data on physico-chemical properties and functional role of protein S-100 have
      been generalized. An analysis of literary data permits making a conclusion that
      the protein interaction with Ca2+ ions plays great part in its action mechanisms.
      Data are presented on the properties of the family of Ca-binding proteins similar
      to protein S-100 as to their structure. Peculiar attention is paid to the
      analysis of this protein function in the cellular nucleus, changing the degree of
      proteins phosphorylation and RNA synthesis.

PMID- 9273725
TI  - [Kinetic regularities of S2'-stimulation of alpha-chymotrypsin].
AB  - Data on the kinetics of S2'-stimulated alpha-chymotrypsin action have been
      presented. It is supposed that the increase of the catalytic action of S2'
      stimulated chymotrypsin occurs at all three stages of the hydrolytic process-at
      the enzyme-substrate complex formation, its transformation to covalent acyl
      enzyme and at the hydrolysis of the latter.

PMID- 9273726
TI  - [Properties of free and bound glycolytic enzymes from the scorpionfish brain. I.
      Hexokinase].
AB  - It was many times shown that hexokinase is tightly bound to cellular structural
      elements form. However, the comparative analysis of free and bound forms
      properties in the fish tissues, in particular in brain, has not been done. This
      analysis was the aim of our experiments with sea scorpion fish brain. Kinetic
      properties, pH and short-time heating influence on the free and bound hexokinase
      activity are described in the paper. Possible physiological role of the both
      enzymes forms is discussed.

PMID- 9273727
TI  - [Properties of free and bound glycolytic enzymes from scorpionfish brain. II.
      Lactate dehydrogenase].
AB  - It is known that a part of lactate dehydrogenase in animal tissues is bound to
      the structural elements. However, if in the tissues of higher animals this part
      is insignificant, in fish tissues it can make tens of percent. The work is the
      continuation of a series of experiments on the comparative characteristic of the
      free and bound glycolytic enzymes in fish tissues, in this case-brain of the sea
      teleost scorpion fish. It was found that the sensitivity of LDH activity to
      different pH values and to the inhibition by high pyruvate concentrations were
      different for the both forms. The enzyme affinity for pyruvate and NADH was 4-6
      times lower in free enzyme. Possible physiological significance of bound LDH form
      existence in the energy supply of the brain is discussed.

PMID- 9273728
TI  - [Properties of free and bound glycolytic enzymes from scorpionfish brain. III.
      Pyruvate kinase].
AB  - It is known that in fish tissues, in particular in brain, a part of pyruvate
      kinase is bound to structural elements. In this work the comparative analysis of
      properties of free and bound pyruvate kinase from the brain of sea teleost
      scorpion fish has been done. The sensitivity to change of pH medium and to
      heating was different in these two forms. The affinity of free enzyme for the
      both substrates was higher, than of the bound one although this difference was
      not reliable because of big individual variation. The difference of Hill
      coefficient in free and bound forms can indicate to different character of
      interaction between the active sites in oligomers of the both forms.

PMID- 9273729
TI  - [Change in activity of microsomal cytochrome P-450-dependent monooxygenases from
      rat liver exposed to chronic low doses of radiation].
AB  - The activity changes of cytochrome P-450-dependent monooxygenases of hepatic
      microsomal fraction were studied in, experimental animals after prolonged
      application (1 month) of low radiation doses (0.258 mkl/kg). The obtained results
      show the increase in catalytic activities of main forms of cytochrome P-450,
      participating in steroid hydroxylation, as well as the decrease in total content
      of cytochrome P-450 in hepatic microsomal fraction and the lowering of its
      demethylase activity.

PMID- 9273730
TI  - [Gene-enzyme alcohol dehydrogenase system and adaptability in Drosophila
      melanogaster].
AB  - As follows from the experiments on the genotypic related populations of
      Drosophila melanogaster with different frequency of ADH allozymes selection for
      postponement of ageing and resistance to hypothermia lead to saturation of
      population with S-allozyme ADH, and genotypic adaptation to ethanol-to increasing
      of frequency of F-allozyme. It is supposed that genotypic adaptation is realized
      by selection of specimens with the most favourable alleles of genes. At the same
      time ontogenetic adaptation is accompanied by biochemical modification of
      existing allozymes.

PMID- 9273731
TI  - [Insulin binding by erythroid cells of swines].
AB  - Insulin binding by erythroid cells of newborn and 1-, 10-, 30-days pigs was
      investigated. The process intensity in piglets was found to decline in the period
      from birth to 30 days of life. The obtained changes were determined by the
      reduced receptors number in high affinity site in early postnatal ontogenesis as
      well as by decrease of receptor affinity constants in 30-days animals. During
      investigated period the level of insulin binding by erythrocytes was conditioned
      by hormone binding ability of "young" erythroid cells, which was found to be high
      in newborn and decreased considerably in 10-30 days pigs. It was established that
      postnatal decrease of insulin binding by erythrocytes occurred simultaneously
      with sharp increase of insulin concentration in animal during the 10-days period
      after birth. So, it is supposed that insulin may be involved in regulation of its
      own receptor number in erythrocytes.

PMID- 9273732
TI  - [Interaction of proteins with platinum and palladium compounds with differing
      biological activities].
AB  - Protein interaction with bioactive platinum and palladium complex compounds was
      studied by solid-phase sorbent assay (SSA), turbidimetry, isoelectric focusing
      and circular dichroism. In SSA reaction ability of metal compounds can be
      represented as follows: [equation: see text] Reaction ability of proteins can be
      represented as follows: hemoglobin > serum albumin > immunoglobulin. The reaction
      products of serum albumin and metal compounds demonstrated more alkaline
      isoelectric points then the intact albumin resulting from adding positively
      charged metal centers [MeCl+, Me2+, [Me(H2O)n]2+, [Me(H2O)nCl]+ to albumin
      molecules. In metal-protein complexes circular dichroism demonstrated the
      diminution of alpha-helix structure percentage if compared with intact albumin,
      the most prominent effect being caused by K2[PdCl]4. The conformational
      distortion of albumin was significant. Metal compounds mostly affected the
      optical activity of S-S-protein bands (251-254 nm). Experimental evidence
      confirmed the hypothesis that platinum metal complexes with high reaction ability
      are less toxic than those with low reaction ability.

PMID- 9273734
TI  - [Interaction of a substance based on phytoecdysteroids (BTK-8L) with components
      of fractionated chromatin from intact rat liver].
AB  - Results of the study of interaction of the phytoecdysteroid preparation (BTK-8L)
      with fractionated rat liver nuclear chromatin were described. It was shown that
      the interaction resulted in the "loosening" of the histone proteins structure
      both in active and repressed chromatin. At the same time the reparative DNA
      synthesis in the repressed fraction was stimulated. The Change revealed might be
      the basis of protective properties of BTK-8L as to chromatin at chloro and
      organophosphorus intoxications.

PMID- 9273733
TI  - [Effect of lipoxygenase derivatives of linoleic acid on functional activity of
      neutrophils].
AB  - The effect of lipoxygenase derivatives of 13-hydroperoxylinoleic acid (13-HPODE)
      and 13-hydroxylinoleic acid (13-HODE) on zymosan-induced chemiluminescence of rat
      neutrophils in vitro was evaluated. It was found that both derivatives inhibit
      functional activity of neutrophils. The extent of inhibition was changed by
      preincubation of neutrophils with arachidonic or linoleic acid. On the other
      hand, in experiments with dogs it was shown that the extent of such inhibition
      considerably increases after ischemia and reperfusion of myocardium. Thus we
      assume that the ratio of lipoxygenase derivatives of arachidonic and linoleic
      acid play the regulative role in functional activity of neutrophils. It was
      concluded, that lipoxygenase derivatives of linoleic acid inhibited the
      neutrophils functional activity.

PMID- 9273735
TI  - [Preparation of monoclonal antibodies to gp51 antigen and their use for early
      diagnosis of bovine leukemia].
AB  - A strain BLV-gp51-V7 of hybrid cells has been obtained that is characterised by
      high specificity as to antigen (glycoprotein gp51). Ascitic tumour appear in
      syngenic mice inoculated with hybrid cells of strain BLV-gp51-V7. Monoclonal
      antibodies were isolated from the ascitic fluid of mice. These antibodies were
      used with the purpose of early diagnosis of cattle leucosis.

PMID- 9273736
TI  - [Effect of the composition of liver perfusion media on functional properties of
      isolated hepatocytes and effectiveness of the isolation method].
AB  - Yield, viability and respiratory activity of hepatocytes isolated from rat after
      liver perfusion by media with various composition have been studied. Collagenase,
      EDTA or citrate were used as disaggregative agents, as well as sucrose or NaCl as
      a main osmotic component. The yield of intact cells after perfusion by different
      media decreased in the following order, collagenase -NaCl-->EDTA-sucrose-
      >citrate-sucrose-->EDTA-NaCl. The rate of endogenous respiration in hepatocytes
      isolated by non-enzymatic methods with EDTA did not depend on the nature of main
      osmotic component and was by 40% lower than in the cells isolated by the
      enzymatic method, however uncoupler-stimulated respiration changed significantly
      less. Replacement of EDTA by citrate increased the rate of endogenous respiration
      and particularly the uncoupler-stimulated respiration. The results show that the
      nature of disaggregative agent and main osmotic component has the influence on
      efficiency of cell isolation method as well as metabolic state of isolated
      hepatocytes. Sucrose leads to the cell shrinkage and have additional to Ca(2+)
      chelator desaggregative effect, citrate plays two functions both as Ca(2+)
      chelator and as mitochondrial substrate.

PMID- 9273737
TI  - [Diagnosis of hemostasis disorders in young children using turbidimetry].
AB  - Practical application of turbidimetrical method for the diagnosis of haemostasis
      disorders in babies with acute intestinal infections (AII) is described. The
      results of plasma biochemical analysis show that disturbances in balance between
      coagulation and fibrinolytic systems takes place in patients with this pathology.
      The correlation between biochemical parameters and clinical characteristics is
      observed. As follows from our data, the phase of the haemostasis disorders in
      babies with AII does not depend on etiology of the disease, but indicates its
      severity.

PMID- 9273738
TI  - [Effect of alpha-tocopherol and nuclear tocopherol-binding proteins on DNA
      polymerase activity of isolated nuclei and nuclear matrix].
AB  - It was shown, that tocopherol addition to the incubation medium increased the DNA
      polymerase activity of isolated rat liver nuclei. This phenomenon was not
      discovered in nuclei of vitamin E-depleted rats. The action of tocopherol changed
      after the extraction of nuclei with triton X-100. In this situation tocopherol
      decreased DNA-polymerase activity of nuclei. The differences between rates of DNA
      synthesis was found after simultaneous addition of tocopherol and fraction of
      tocopherol-binding protein to the nuclei of normal and vitamin E-depleted rats.
      In this case DNA-polymerase activity of normal nuclei increased, but did not
      change in nuclei of vitamin E undernourished rats. The difference between them
      was about 30%. The differences between DNA-polymerase activity of normal and
      vitamin E-depleted rats after the addition of tocopherol and fraction of
      tocopherol-binding protein were also found in nuclear matrix preparation. It was
      supposed that tocopherol was able to take part in functioning of cell nuclei
      modulating DNA synthesis as well.

PMID- 9273739
TI  - [Effect of adenosine triphosphate on the cleavage of H1 histones in nuclei of rat
      spleen and liver].
AB  - Proteolysis of histones H1b and H1(0) is observed after the incubation of rat
      spleen nuclei at 37 degrees C during 1 hour. Adenosine triphosphate, inorganic
      pyrophosphate and nicotinamide adenine dinucleotide decrease the digestion of
      histone H1b. ATP, PP1 and NAD+, in the case of 3 hours incubation, do not affect
      proteolysis of H1 histones in rat spleen nuclei. The incubation of rat liver
      nuclei at 37 degrees C during 1 hour leads to a decrease of the amount of histone
      H1b and, to much more extent, H1a. In this case ATP, PP1 and NAD+ increase
      proteolysis of histone H1a but practically do not affect proteolysis of H1b.
      After 2-hours incubations histone H1a is completely digested but histone H1b is
      partially preserved: ATP in this case, as well as in spleen nuclei, decreases
      proteolysis of histone H1b. During the 3 hours incubation, when histones H H1a
      and H1b are completely digested, partial digestion of histone H3 being observed,
      ATP does not prevent from proteolysis of histone H1b. A protein appears between
      the H2A and H4 histones after heating at 37 degrees C in both spleen and liver
      rat nuclei. Neither ATP nor PP1 and NAD+ affect the amount of this protein. It is
      suggested that the location of histones H1a and H1b in different chromatin
      domains determines the digestion of these histones by ATP-dependent proteinases.

PMID- 9273740
TI  - [Sources of convertible energy in Staphylococcus].
AB  - It has been found out that Staphylococcal cells have two basic convertible energy
      sources--the intercell ATP pull and electrochemical potential of hydrogen ions.
      The ATP synthesis takes place under laying the membrane potential by creation of
      K+ gradient in valinomycin presence and in the transmembrane gradient pH. The
      magnitude of the transmembrane electrical potential difference was determined and
      it reached from 100 to 160 mV within pH range of 5.0-8.0 at the same time pH
      dropped from 90 to 40 mV. The protonmotive force magnitude remains invariable
      (191-198 mV) at the pH range 5.0-8.0.

PMID- 9273741
TI  - [Structure and mechanism of functioning of centers of fibrin polymerization].
AB  - Fibrinogen takes part in a lot of physiological and pathological processes in the
      organism. Its most important function consists in preventing blood leakage
      through the injured wall of the blood vessel. Proteolytic enzyme thrombin
      generated in the site of the injury splits low-molecular fibrinopeptides A and B
      from fibrinogen and transforms the latter into the monomeric fibrin which is
      spontaneously polymerized with formation of a clot of blood closing a lumen of
      the injured vessel. Fibrin polymerization that completes the stages of blood
      coagulation is the example of self-assembling of supermolecular biological
      structures in blood coagulation system. Clearing-up of this process mechanisms is
      of great theoretical and practical importance, in particular, for clinical
      medicine connected with treatment of hemorrhages and thromboses.

PMID- 9273743
TI  - [Effect of phospholipase A2 on H+-ATPase in the plasma membrane of H+-ATPase in
      maize root cells].
AB  - The plasma membrane H(+)-ATPase which plays a central role in plant cell
      physiology is lipid-dependent enzyme. Lipid composition of plasma membrane can be
      modified by the action of endogenous phospholipases. Recently it has been
      supposed that the plasma membrane phospholipase A2 participates in phytohormonal
      signal transduction on the H(+)-ATPase protein. We have investigated the effect
      of phospholipase A2 on the H+ ATPase activity in plasma membrane preparations
      isolated from 7-days corn seedling roots. The exogenous phospholipase A2 from
      snake venom and lipid hydrolysis products of the phospholipase A2-catalysed
      reaction have been used. It was found that the phospholipase A2 increased plasma
      membrane H(+)-ATPase activity during first 15 sec. but inhibited it under the
      longer exposition. Examination of lyso-derivatives effect on plasma membrane
      preparations demonstrated a 2-3-fold increasing of their H(+)-ATPase activity by
      lysophosphatidylcholine whereas the effect of lysophosphatidic acid was expressed
      to higher extent. Studying of the effects of unsaturated free fatty acids as the
      second hydrolysis product has shown that linolic and linolenic acids activated
      the plasma membrane H(+)-ATPase at concentration of 10 microM but inhibited it at
      higher concentrations. Exposition of plasma membranes with the phospholipase A2
      or fatty acids shifted H(+)-ATPase pH optimum from pH 6.5 to pH 7.0. The role of
      endogenous phospholipase A2 in regulation of plasma membrane H(+)-ATPase activity
      has been under discussion.

PMID- 9273744
TI  - [Seasonal dynamics of the content of proteins inhibiting trypsin-like proteases
      in the leaves of common oak (Quercus petraea Liebl.)].
AB  - After the successive purification of proteins-inhibitors of trypsin-like
      proteases using the methods of chromatography on DEAE-cellulose, trypsin-agarose
      and sephadex G-50, their numerous forms with the values of molecular weight 3.5;
      6.3; 12.5; and 25.0 kDa have been found out. From spring to autumn the increase
      of the absolute content of proteins-inhibitors of all types was accompanied by
      the change of their relative content. The more than by an order increase of
      general content of proteins inhibitors is discussed from the position of their
      stress origin as a result of the effect of unfavorable ecological factors.

PMID- 9273742
TI  - [Activation of cGMP-dependent protein kinase from spleen lymphocytes of rats
      exposed to radiation].
AB  - We have emanated and partially refined cGMP-dependent protein kinase from
      cytosolic fraction of lymphocytes. 12 hours after X-irradiation of animals in the
      doses of 0.5 and 1 Gr. Optimal conditions for the occurrence of
      phosphotransferase reaction have been also fixed. Concentration of enzymes
      protein was 0.4 mg/ml, Mg(2+)-10 mM, pH-7.5-8.0 and incubation time 20 min. The
      purified enzyme was maximally active at 10(-7) M cGMP. Protein kinase activity
      had a dose-dependent character: the doses being increased the effect becomes
      stronger.

PMID- 9273745
TI  - [Effect of inhibitors of energy-dependent Ca2+-transporting systems on calcium
      pumps of a smooth muscle cell].
AB  - Comparative investigation of sensitivity of calcium pumps of sarcolemma,
      endoplasmic reticulum and mitochondria of the smooth muscle to some inhibitors of
      energy-dependent Ca(2+)-transporting systems has been carried out in experiments
      made using the isotope method (45Ca2+) on the fraction of plasmatic membranes and
      suspension of chemically scanned cells of myometrium as well as on the
      preparation of highly purified Ca2+, Mg(2+)-ATPase which was solubilized from
      plasmatic membrane of uterus myocytes. It is proved that the calcium pump of
      mitochondria is selectively inhibited by ruthenium red (imaginary inhibition
      constant K, is equal to 0.6 microM); it is nonselectively inhibited by o-vanadate
      (Ki = 0.6 mM), p-chloromercuribenzoate (Ki = 3.2 microM) and cosine (Ki = 2.1
      microM), but is not sensitive to the effect of thapsigargin and cyclopiasonic
      acid. Mg2+, ATP-dependent calcium pump and transport Ca2+, Mg(2+)-ATPase of
      plasmatic membrane are nonspecifically inhibited by o-vanadate (the value Ki
      equals 45.0 and 5.0 microM, respectively) and by cosine (Ki = 0.8 microM in the
      both cases); this calcium pump is also nonspecifically inhibited by p
      chlormercury benzoate (Ki = 3.2 microM), but it is not sensitive to the effect of
      ruthenium red. Mg2+, ATP-dependent calcium pump of endoplasmic reticulum is
      selectively inhibited by tapsigargin (Ki = 2.0 nM) and cyclopiasonium acid (Ki =
      0.3 microM), but, like calcium pumps of mitochondria and plasma membrane, it is
      nonspecifically inhibited by o-vanadate (Ki = 45.0 microM); by p
      chlormercurybenzoate (Ki = 0.6 microM) and eosin (Ki = 0.8 microM), but it is not
      sensitive to the effect of ruthenium red. Data that have been obtained can be of
      use for the further development of the ideas about biochemical regularities of
      Ca(2+)-dependent control of contraction-relax of the smooth muscles,
      identifications of energy-dependent calcium pumps of smooth cells and finding out
      of structure-functional organization of these pumps.

PMID- 9273746
TI  - [Interaction of C27-sterols with erythrocyte membranes].
AB  - It is established in the in vitro experiments that the interaction of natural C27
      sterols: cholesterol, 7-dehydrocholesterol, cholecalciferol (vitamin D3),
      calcitriol (1 alpha, 25-dihydroxyvitamin D3), ecdysterone (20-hydroxyecdysone)
      and 2-deoxyecdysterone modulate both lipid and protein phases of human
      erythrocyte membrane at the concentration range 10(-6)-10(-12) M. These effects
      depend on the sterols concentration and on the number and position of hydroxy
      groups in the sterol molecules.

PMID- 9273747
TI  - [Effect of radiation on the structure of model and natural biomembranes using
      differential scanning calorimetry].
AB  - A novel method of DSC studies of biomembranes has been proposed, making it
      possible to investigate the influence of ionizing radiations upon the structure
      of water dispersions of phospholipids and phospholipid-based systems of natural
      origin, e.g., rat liver homogenates and erythrocyte ghosts. It is shown that in
      certain concentration range of the bonded water thermograms obtained are
      reproducible during heating and cooling cycles and can give information about
      phase state, supramolecular ordering and radiation sensitivity of the systems
      under consideration.

PMID- 9273748
TI  - [Effect of x-irradiation on the structural and functional characteristics of rat
      erythrocytes and activity of individual enzymes of glycolysis].
AB  - The activity of glycolytic enzymes (lactate dehydrogenase, pyruvate kinase,
      hexokinase), content of metabolites (lactate, pyruvate, ATP, 2,3-DPG) and
      haemolytic stability of rat erythrocytes at the action of chronic X-irradiation
      at a daily dose 0.258 mC/kg, 2.58 mC/kg, 5.16 mC/kg during 90, 60 and 30 days,
      accordingly, have been investigated. It was shown, that the glycolytic enzymes
      activity of female rats in different seasons may vary in wide limits. A general
      tendency to the decrease of lactate dehydrogenase activity is revealed, but the
      beginning effects under the irradiation at a daily dose of 2.58 mC/kg and 5.16
      mC/kg may be differently directed. The analogous tendencies are found in the
      change of hexokinase activity. The changes in pyruvate kinase activity correlated
      with erythrocytes haemolytic stability. The data obtained prove that changes in
      the direction of glycolytic enzymes activity under the irradiation depend on the
      initial level, which is caused by seasonal peculiarities of physiological state.

PMID- 9273749
TI  - [Purification of lectin from Paris quadrifolia L. and comparison of its
      carbohydrate-binding specificity with other lectins of the Liliaceae family].
AB  - Lectin from rhizomes of Paris quadrifolia I. was purified by affinity
      chromatography on cross-linked ovomucine with yield of 75 mg per 1 kg of fresh
      rhizomes. Purified lectin gave a single band on gel disk electrophoresis at pH
      4.5 and two bands at pH 8.9. Electrophoresis in gradient 15-20% polyacrylamide
      gel in the presence of DS-Na at pH 8.9 has revealed two distinct bands with Mm
      12.8 and 11.5 kDa. Gel chromatography on Sephadex G-200 has discovered two
      proteins with Mm 50 and 102 kDa. The agglutinating activity is inhibited by N
      acetylneuraminic acid and several sialyl-glycoproteins. Lectins with such
      specificity were also discovered in grasses Scilla bifolia I, Gagea lutea I. and
      Polygonatum multiflorum (L) All.

PMID- 9273750
TI  - [Effect of paracetamol on the microsomal oxidation, oxidative phosphorylation and
      liver mitochondria swelling in rats of various ages].
AB  - The effect of hepatotoxic dose of paracetamol (800 mg per kg, intraperitoneally,
      once a day during two days) on the system of microsomal oxidation, respiration,
      oxidative phosphorylation and high amplitude swelling of liver mitochondria was
      studied on 1-, 4- and 30-months old Wistar male rats. It has been shown, that
      paracetamol injection leads to the decrease of content of cytochrome P-450, to
      disorders of the function of monooxygenase system (the aminopyrine-N-demethylase
      and aniline hydroxylase activities were diminished), mitochondria macrostructure
      (the mitochondria high amplitude swelling time was decreased) and function (the
      respiratory control was decreased). These alterations have been observed to
      manifest to more extent in the liver of young rats as compared with old ones.

PMID- 9273752
TI  - [Treatment of habitual abortion].

PMID- 9273753
TI  - [Human herpesvirus 8. A Kaposi sarcoma-associated herpesvirus?].

PMID- 9273751
TI  - [Steroidogenesis in rat testes in chronic alcoholic intoxication and addition of
      ethanol in vitro].
AB  - The influence of ethanol on steroid biosynthesis in microsomal fraction of rat
      testes has been studied. Addition of ethanol in vitro as well as chronic
      alcoholization have been shown to change the activity of enzymatic ensembles of
      steroidogenesis in testes. A significant decrease in 3 beta-hydroxysteroid
      dehydrogenase activity, revealed in all experiments, has permitted the authors to
      conclude that this phenomenon is of special significance for the realization of
      gonads hormonal response to ethanol.

PMID- 9273754
TI  - [A hematologist on the Internet].

PMID- 9273755
TI  - [Habitual abortion. A review of etiology, diagnosis and treatment with emphasis
      on immunonological factors].
AB  - Almost 1% of women who attempt pregnancy will experience recurrent miscarriage.
      The majority of traditionally accepted causes of recurrent miscarriage lack
      proper documentation and the evidence for the majority of treatments is sparse.
      An increased level of midfollicular phase luteinizing hormone seems to be
      associated with some cases of recurrent miscarriage. Many autoantibodies are
      found with increased frequency in women with recurrent miscarriage, and they seem
      to be associated with an increased risk of adverse pregnancy outcome. This may
      indicate that the autoantibodies per se or associated immunological phenomena are
      risk factors for the condition. Polygenically determined immunological phenomena
      seem to play an important role. Treatment of recurrent miscarriage by
      anticoagulation, allogeneic lymphocyte immunization or intravenous immunoglobulin
      is under evaluation in controlled trials.

PMID- 9273756
TI  - [Vena saphena magna in situ bypass to the ankel and foot. A prospective
      assessment of results of 101 procedures in 94 patients with threatening
      amputation].
AB  - The results of 101 in situ by-pass operations to the ankle and foot are given.
      Seventy-five percent of the patients had other arteriosclerotic manifestations
      and 55% were diabetics. Ninety-nine percent of the operations were limb salvage
      surgery. The accumulative secondary patency rate was 87% after one month and 65%
      after three years. The results did not differ from by-pass surgery to the crural
      arteries. The wound complication rate was 16% with an infection rate of 7% and
      the major amputation rate was 8% after one month and 10% after three years. The
      survival of this selected group of patients was lower than a group of sex- and
      age-matched controls. The long term results of this type of advanced by-pass
      surgery in limb threatening ischaemia are very satisfactory and should be a must
      in every vascular surgeon's armamentarium.

PMID- 9273757
TI  - [Pernicious anemia and risk of cancer in Denmark].
AB  - The cancer pattern was investigated among 5072 patients with a discharge
      diagnosis of pernicious anaemia during 1977-1989, using data from the Danish
      Hospital Discharge, Central Population and Cancer registries. During 1-15 years
      of follow-up we found, in line with earlier reports, two to three-fold increases
      in the risk of cancer of the stomach, buccal cavity and pharynx, which were
      unchanged when the analysis was stratified according to sex and duration of
      follow-up. A previously reported positive association with haematological cancers
      could only be found for short term follow-up to indicate that no real association
      exists. Our cohort of patients with pernicious anaemia experienced significantly
      reduced risks of cervix and non-melanoma skin cancer.

PMID- 9273758
TI  - [Immunoglobulin E and cell-mediated hypersensitivity in an unselected adult
      population. The Glostrup Allergy Study].
AB  - In this study, we have assessed the relationship between immunoglobulin E
      mediated and cell-mediated hypersensitivities in an unselected population living
      in Western Copenhagen, Denmark. A total of 793 subjects, aged 15-69 years, were
      studied. Measurements of serum immunoglobulin E level, prick tests with
      aeroallergens and patch tests with environmental haptens were performed in 561
      (70.7% of 793) subjects. One or more positive prick tests were present in 28.4%,
      and contact sensitization occurred in 15.2%. When adjusted for the effects of age
      and sex, the probability of contact sensitization to one or more haptens was
      independent of serum immunoglobulin E level (the odds ratio value (OR)=1.0; 95%
      confidence interval (CI)=0.7-1.4), and the probability of contact sensitization
      was independent of the number of positive prick tests (OR=1.0; CI=0.8-1.2).
      Contact sensitization appeared to be independent of enhanced immunoglobulin E
      responsiveness in an unselected adult population.

PMID- 9273759
TI  - [Traumatic tricuspid valve insufficiency].
AB  - We report a case of tricuspid insufficiency in connection with blunt chest
      trauma. The patient was involved in a car accident. The central venous catheter
      showed a right ventricular pressure curve, suggestive of a tricuspid valve
      insufficiency. A transoesophageal echocardiographic examination supported this by
      revealing a papillary muscle rupture. This kind of injury has been seen more
      frequently during the last 35 years, partly because of better diagnostic
      procedures and a better understanding of the pathology. The decelerating force in
      the right ventricular chamber produces a regurgitation thereby initiating rupture
      of the papillary muscle and/or the chordae tendinae. In a literature study twelve
      out of thirteen patients were involved in car accidents. Some of them had a
      dominant V-wave in the venous pulse curve, but no clinical observation is
      directly diagnostic. Therefore, cardiac lesions should be kept in mind whenever
      there is a history of blunt chest trauma. The best diagnostic approach is
      echocardiography.

PMID- 9273761
TI  - [Chordae tendinae reconstruction in ischemic mitral valve insufficiency].

PMID- 9273760
TI  - [Poisoning with a reversible and selective monoaminooxidase inhibitor].
AB  - Two cases of poisoning with moclobemide are presented. Moclobemide is a
      reversible inhibitor of the monoamine oxidase type A (RIMA). Intoxication with
      moclobemide is according to previously published case stories benign. Both
      patients described presented severe symptoms, such as convulsions, coma, muscle
      rigidity and respiratory failure. One of the patients, a 37-year-old woman, also
      suffered cardiovascular collapse and elevated body temperature (more than 41.9
      degrees C), which was treated successfully with dantrolene and norepinephrine.
      The symptoms match the diagnostic criteria for serotonin syndrome. The possible
      reasons why the two patients suffered life-threatening complications and the
      treatment of serotonin syndrome are discussed.

PMID- 9273762
TI  - [Food and cancer prevention].

PMID- 9273763
TI  - [Malaria prophylaxis].

PMID- 9273764
TI  - [Development of HIV/AIDS in Sweden and Denmark. There is a difference!].

PMID- 9273765
TI  - [Urinary bladder tumors. Report of the Danish Bladder-cancer Committee 1993].

PMID- 9273766
TI  - [Comment on U. Wolfhard: Recycling of used implantable defibrillators].

PMID- 9273767
TI  - [Work disability].

PMID- 9273768
TI  - [Who should pay? Why rationing in health care is unavoidable today].

PMID- 9273769
TI  - [Late diabetic sequelae].
AB  - Diabetic patients are exposed to higher risk of morbidity and mortality. However,
      it is difficult to define this in advance and to predict the degree of inability
      for work. The risk is depending on type of diabetes, age of manifestation, age of
      the patient course and duration of the disease and mainly from glycemic control.
      Educational programs may markedly ameliorate the overall situation and decrease
      of risk of late complications which may threat kidney, eyes, nerves and the
      cardiovascular system. However, it is an erroneus notion that most diabetics may
      be crippled by complications of their disease which may result in unwarranted
      bias against them in both work and leisure activities. Most diabetics may
      undertake any occupation or hobby, of course with some exceptions when
      hypoglycemia due to insulin or hypoglycemic agents represents risk for themselves
      and other persons. Those patients may not serve as pilots and cannot hold public
      service vehicle driving licences. They should not take over the supervision in
      power-stations etc. Ordinary driving licences can be held by diabetic patients if
      on insulin or not, provided that they are otherwise physically fit and do not
      suffer from blackouts. From many studies it is known that the rate of accidents
      is not higher with respect to diabetic patients than in the normal population.
      Life assurance premiums are often raised by amounts which depend on the result of
      a medical examination but it is very important that the judgement is not made on
      the basis of a single checkup at a given time. To get information about the
      presence or development of late complications which have a very broad spectrum it
      is necessary to have insight into the course of the metabolic disorder and the
      tendency of worsening or amelioration.

PMID- 9273770
TI  - [The rheumatoid patient as back pain patient. Diagnosis and differential
      diagnosis of seronegative spondylarthropathies].
AB  - Based on an epidemiology study the frequency of back pain in the population was
      established by forty percent. Otherwise only thirty percent of patients with
      backache are diagnosed definitely by practitioners. In view of these
      circumstances the 1991 published diagnosis criteria for spondylarthropathies are
      a helpful work in definition of spondylarthropathy patients. Furthermore a new
      described autoantibody specifically for spondylarthropathies seems to be helpful
      for this diagnosis of these systemic rheumatic diseases.

PMID- 9273771
TI  - [Femur head necrosis in the adult. Diagnosis, therapy, legal aspects for
      insurance medicine].
AB  - Early recognition and adequate therapy of necrosis of the head of the femur in
      adult patients in increasingly gaining importance since they considerably
      influence the permanent loss of function and reduction of the earning capacity of
      people of working age. Presently, MRT examination is the most conclusive method
      for the early stage of necrosis of the head of the femur. After the introduction
      of microsurgical methods, new therapeutic measures for avascular necrosis of the
      head of the femur are available, apart from conventional surgical methods to
      relieve the necrotic areas and the so-called metabolic irritation drilling.
      Direct vascular-supply, autologous, heterotopic, corticospongiose transplants in
      the necrotic head of the femur are suited to re-establish circulation in the
      necrotic area. This involves a considerable operative scope of work.

PMID- 9273772
TI  - [Cholesterol and coronary sclerosis].
AB  - This paper defines the terms logic, cause, and risk. Furthermore this paper
      shows; High serum cholesterol concentrations do not cause the sclerosis of the
      coronary arteries. Therefore, interventions are useless.

PMID- 9273773
TI  - [Fat embolism--a too infrequently determined pathoanatomic diagnosis].
AB  - In 1993, pulmonary fat embolism occurred in 92 cases (17%) out of 527 clinical
      autopsies. It was found in 62% of patients who had suffered bone fractures, in 9%
      with soft tissue surgery and in 53% after resuscitation; non-traumatic fat
      embolism was present in 6% of the cases. The comparison group of 50 persons with
      lethal polytrauma revealed pulmonary fat embolism in 52% of the cases. Bone
      marrow embolism and microthrombi accompanied fat embolism of the lungs;
      furthermore some of the persons with pulmonary fat embolism also expressed minor
      degrees of renal (55%) and cerebral (25%) fat emboli. A retrospective analysis of
      the clinical data revealed no specific symptoms: a so called fat embolism
      syndrome had not been discovered clinically in any of the cases with
      histologically proven fat embolism. The significance of pulmonary fat embolism as
      a cause of death with regard to histological and clinical findings is discussed.

PMID- 9273774
TI  - [Expert systems in risk assessment. Risk or opportunity?].
AB  - Experts underwriting systems in the risk selection of individual life insurance
      have a high place value and are, in future, indispensable in the daily
      underwriting process. The chance to reduce drastically dual operations enables
      the insurance companies to make more cost-efficient underwriting decisions. The
      rapidly advancing technology develops not only new dimensions for individualism
      and for providing customer service but also for a fast underwriting process which
      is of great benefit to the insurers who are up against stiff competition. The
      qualified underwriter and the physician will be relieved of standard work and
      have more time in investing their knowledge and know-how in the underwriting
      process which calls for an absolutely individual reflection. New activities are
      inevitably ahead of this group of persons: Maintenance and attendance of the
      experts system! A task with which the quality of such a system stands and falls.
      We are expectant to see what the future has in store for this field.

PMID- 9273775
TI  - [Accounting for conformational flexibility of molecules in structure-property
      studies].
AB  - Methods for investigations of "structure-property" relationships for
      conformational flexible molecules have been described. By means of exhaustive
      conformational search the methods allow one to find: the active chemicals for a
      specific biological interaction, the similarity between 3D structures of
      molecules and common reactivity patterns. The OASIS-COREPA approach accounting
      for conformational flexibility of chemicals has been employed for modeling of
      reintegration of the retinal derivatives into bacterioopsin in order to find the
      common structural requirements of protein molecule to retinoids' molecules. The
      common reactivity pattern conditioning the high biological activity has been
      elucidated. The results are mechanistically reasonable confirming the hypothesis
      for two-stage process of reintegration and allowing prediction of novel and
      biologically active derivatives.

PMID- 9273776
TI  - [Glucocorticoid receptor function in hemorrhagic shock and its treatment by
      calcium antagonist].
AB  - In the present study a function of glucocorticoid receptors II and III types of
      rat liver cytosol has been investigated in the hemorrhagic shock and its
      treatment by a calcium antagonist A-1 using radioreceptor methods using labelled
      steroid ligands. Glucocorticoid receptor density, association and dissociation
      constants of ligand-receptor complexes has been measured via Scatchard analysis
      of corticosteron concentration in blood serum has been determined using
      radioimmune kits. In experiments in cats system hemodynamics and metabolism
      characteristics have been evaluated. It was demonstrated that together with
      expressed blood circulation and metabolic disturbances in the hemorrhagic shock
      the glucocorticoid receptor function was considerably decreased. Under the
      influence of the calcium antagonist A-1 glucocorticoid receptors' type II density
      increased and type III receptor density decrease took place. The drug increased
      protein content in the liver cytosol. Hemodynamics indices normalization and
      increase of the animals' life length indicated an expressed antishock activity of
      the A-1 calcium antagonist which apparently associated with its modulating
      influence on the glucocorticoid receptor function.

PMID- 9273777
TI  - [Effect of chrysotile-asbestos and zeolites dust on generations of reactive
      oxygen species by alveolar macrophages and granulocytes].
AB  - Different characteristics of the influence of dusts of chrysotile--asbestos,
      mordenite, erionite and klinoptilolite on the total generation of the active
      forms of oxygen by the alveolar macrophages and the generation of O2- and H2O2 by
      the granulocytes give the possibility to connect some of these characteristics
      with the peculiarity of biological action these dusts. It is discovered the most
      strong activating properties has the dust of chrysotile--asbestos, and the most
      cytotoxic effect has the dust of klinoptilolite.

PMID- 9273778
TI  - [Bio-antioxidant activity of 3,5-di-tert-butylpyrocatechol and its influence on
      hypoxia, inflammation, pain and burns].
AB  - The bioantioxidant activity of the synthesized by us on the base of the diatomic
      phenol compound--3,5-di-t-butylpyrocatechol--has been studied. It was shown that
      this substance exhibits more pronounced antioxidant properties than tocopherol on
      the lipid peroxidation process in the rat brain homogenate appears in
      concentrations right up to 10(-8)-10(-7) M. Antioxidant effect of 3,5-di-t
      butylpyrocatechol protecting action correlation has been found in the simulation
      of such pathological organism states as hypoxia, inflammation, burn, pain. All
      above mentioned results confirms the expedience of search for new drugs based on
      diatomic phenols.

PMID- 9273779
TI  - [Influence of lead on metabolism of vitamins B group in alimentary iron deficient
      rats].
AB  - Experimentally induced lead poisoning especially under simultaneous iron deficit
      leads to the development of secondary thiamine insufficiency. Erythrocyte
      riboflavin content and erythrocyte glutathion reductase and aspartate
      aminotransferase activities have been demonstrated to be increased. Lead
      treatment is accompanied with the increase of urinary excretion of riboflavin, 4
      pyridoxic acid and 1-vtthylnicotinamide in rats fed with adequate diet. Thus lead
      intoxication and iron deficiency influence vitamin B group metabolism.

PMID- 9273780
TI  - [Identification physico-chemical properties and immunochemical characteristic of
      prostate specific antigen and its complexes with protease inhibitors].
AB  - The study of the PSA complexes with the protease inhibitors has confirmed the
      opinion of possible existence the complexes of the PSA with a2-macroglobulins and
      a1-antihymotripsines in blood serum. The immunoenzyme analysis of the PSA and its
      complexes has made it possible to establish the normal level of the PSA
      corresponding complexes in donors blood serum. There are reasons to suppose, that
      the quantitative analysis of the PSA and its complexes with the protease
      inhibitors can be used for the early diagnosis of PC and its differential
      diagnosis with the prostate benign hyperplasia. In our opinion, the effect of the
      complex approach can be more informative than the ordinary PSA detection.

PMID- 9273781
TI  - [Involvement of monoamine oxidases in formation of 4-hydroxyphenylethanol, major
      component of tribulin A].
AB  - Pathways of 4-hydroxyphenylethanol formation were studied in the bovine brain.
      Incubation of brain homogenates with tyramine or tyrosine increased 4
      hydroxyphenylethanol content only in the presence of NADH. Tyramine produced more
      pronounced augmentation of 4-hydroxyphenylethanol content than tyrosine. Tyrosine
      preparations were not contamined with tyramine. This suggests that 4
      hydroxyphenylethanol may be formed from tyramine and tyrosine in NADH-dependent
      process. Preincubation of homogenates with 0.1 mM pargyline completely inhibited
      monoamine oxidases A and B and prevented NADH-dependent formation of 4
      hydroxyphenylethanol from tyramine. The latter suggests that MAO is involved in
      formation of 4-hydroxyphenylethanol.

PMID- 9273782
TI  - [Change of isoforms' spectrum of alpha-L-fucoside secreted by affected cells in
      some hereditary lysosomal diseases].
AB  - In vitro it was studied the isoform spectra of the intracellular and secreted
      alpha-L-fucosidase from skin fibroblasts of patients with Fabry disease
      (glycolipidosis), Hurler and Sanfilippo D diseases (mucopolysaccharodosis, types
      I and III) and in the normal state was studied. It was shown that the multiple
      form profile of secreted alpha-L-fucosidase in patients fibroblasts was changed
      as compared to that in control: the pathological cells were characterized by
      expression of more basic isoforms of alpha-L-fucosidase. The changes were similar
      to those in sucrose-loaded normal cells, modelling storage disease. The data
      obtained allow the suggestion that the intracellular accumulation of compounds
      whose hydrolysis was disturbed on a hereditary deficiency of enumerated
      glycosidases can influence the posttranslational processing of alpha-L
      fucosidase, the enzyme which is not primary affected in these disorders. These
      data allow the conclusion that the high phenotypic heterogenity of lysosomic
      storage diseases is possibly due to the influence of so-called epigenetic factors
      involving the changes in properties of such glycosidases as are not associated
      with a primary hereditary defect.

PMID- 9273783
TI  - [Method of estimation of lysozyme activity in serum with chitin azure as
      substrate].
AB  - The method of estimation of lysozyme activity in serum when chitin azure is used
      as substrate is described. The basis of incubation medium is 0.1 M acetate
      buffer, pH 5.0. It was judged about activity of lysozyme by fluorescence of azure
      in incubation medium at the end of three hour incubation at 37 degrees C after
      separation on non-reacted chitin azure by short time centrifugation. It was shown
      that development of wound infection is accompanied by increasing of chitinase
      activity of lysozyme in serum.

PMID- 9273784
TI  - [Temperament as a prerequisite of creative capabilities].
AB  - Temperamental and creative characteristics were compared in three groups of
      subjects who manifested a bent for creative activity. The groups differed in
      their age: 14-year-old schoolchildren of architectural class (n = 20), 18 to 20
      year-old students of architectural institute (n = 94), and 25 to 45-year-old
      professional architects (n = 25). The temperamental properties were measured
      using the STQ method. The creative characteristics were evaluated by E. P.
      Torrance's non-verbal tests of creative thinking. In the structure of creative
      abilities, only two creative characteristics, i.e., fluency and flexibility,
      correlated at the statistically significant level with temperamental properties
      in all the age-specific groups under study. The closest correlations were found
      with plasticity and emotionality of temperament both in object-related and
      subject-related spheres.

PMID- 9273785
TI  - [The relationship of visual illusions to the frequency and phase shift of
      rhythmic photostimulation synchronized with the EEG alpha wave].
AB  - Under flicker stimulation through the closed eyes, synchronized with different
      phases of the EEG alpha wave, all 18 subjects systematically perceived the
      illusory visual objects (ring, circle, spiral, or curvilinear grid). Most
      frequently, they saw a ring or a circle, a little less frequently, a three
      dimensional spiral, and at last-a curvilinear grid. The incidence of the ring and
      spiral illusion was the highest when the stimulation frequency strictly coincided
      with the individual dominant frequency of the alpha-rhythm. On the contrary, the
      grid illusion appeared more frequently when the stimulation frequency differed
      from that of the alpha-rhythm by 1-2 Hz. No significant effect was found of the
      alpha wave phase, which triggered the photostimulation, on the probability of the
      illusion perception. The revealed phenomena are probably explained by summation
      of the spreading alpha wave (the "scanning" hypothesis) with the isorhythmical
      afferent excitation evoked by flashes due to the quasi-stroboscopic effect.

PMID- 9273786
TI  - [Fast positive cortical potentials of the human cerebral hemispheres to visual
      stimuli evoking saccades].
AB  - The EEG was recorded in 7 healthy subjects aged 20-25 years according to the
      International 10-20 System in the frontal and parietal derivations (F3, F4, Pz,
      P3, P4) during the saccades related with the visual stimuli. A complex of fast
      (positive and negative) event-related potentials was recorded in response to
      visual stimulation before the saccade onset. The amplitude and spatial
      distribution of these potentials depended on the saccade latency, order of
      stimuli presentation, personality of a subject etc. The results suggest that the
      early positive potentials observed in the saccade latent period reflect the
      activation of the cortical structures which participate in programming and
      initiation of saccades.

PMID- 9273787
TI  - [The effect of hippocampectomy on the acquisition and recovery of a conditioned
      reflex to time in rats].
AB  - The dynamics of time conditioning was studied before and after electrolytic
      lesions of the dorsal hippocampus in rats. Hippocampectomy disturbed the recovery
      of time conditioned reflex which was consolidated before surgery. The change
      depended on the extent of hippocampal lesion. In rats after the limited
      hippocampectomy the conditioned reflex recovered faster than in sham-operated
      animals. However, after more extensive lesions the process of conditioning
      recovery was delayed. In hippocampectomized animals without previous training the
      time conditioned reflex was not formed irrespective of the volume of brain
      lesion. Injection of amphetamine (0.05 mg/kg) was ineffective in this case.

PMID- 9273788
TI  - [The individual characteristics of dogs with a free choice of the probability and
      value of food reinforcement].
AB  - The tactics of choice between two feeders after changing the probability and
      quality of food reinforcement in one of them was studied in 4 freely behaving
      dogs. The conditioned stimulus was not changed. It was shown that choice tactics
      differed between the dogs even under conditions of equal 100% probability of food
      reinforcement in both the feeders. Decrease in probability of presentation of
      higher-quality food in one of the feeders increased the incidence of choice of
      this feeder only in one dog. This dog was characterized by a higher rate of the
      dynamic stereotype conditioning in response to the number of presentations of
      cups with food in each feeder. The dogs preferred the constant reinforcement when
      food in the two feeders was of the same quality but presented with different
      probability.

PMID- 9273789
TI  - [Interneuronal relationships in the basolateral amygdala of cats trained for
      choice in the quality of food reinforcement].
AB  - The alimentary instrumental conditioned bar-pressing reflex was elaborated in
      cats by the method of "active choice" of either short-delayed reinforcement with
      bread-meat mixture of delayed more valuable reinforcement with meat. The animals
      differed in behavior strategy: some animals preferred bar-pressing with the long
      delay (the so-called "self-control" group), other animals pressed the bar with
      short delay (the so-called "impulsive" group). The multiunit activity in the
      basolateral amygdala was recorded with chronically implanted nichrome
      microelectrodes. The interactions between the spike trains of the neighbouring
      neurons selected from the multiunit activity were evaluated by means of
      statistical crosscorrelation analysis. It was shown that the number of
      correlations between the discharges of neurons was significantly higher in the
      "impulsive" cats. In both groups the number of cross-correlations was maximal in
      cases of a difficult choice, i.e., during the omission of the conditioned bar
      pressing response. In "impulsive" cats the number of interneuronal correlations
      was highest with the latencies in the range of 0-30 msec. We suggest that the
      basolateral amygdala is involved in the system of structures which determine the
      individual-typological characteristics of animals.

PMID- 9273790
TI  - [The "polarization" hunger dominant (the behavioral characteristics and EEG
      spectral analysis)].
AB  - A new experimental model of dominant was developed by the author, the so-called
      "polarization" hunger dominant created by application of weak direct current to
      the lateral hypothalamus in combination with a sound stimulus. There was an
      increase in the delta component of the electrical activity of the left parietal
      cortex (the dominant focus) while the EEG spectral power of the other cortical
      areas, lateral and ventrolateral hypothalamus decreased in the slow-wave ranges.

PMID- 9273791
TI  - [Cross-correlational analysis of the neuronal connections of the cerebellum in
      the waking rabbit].
AB  - The methods of cross-interval and crosscorrelation analysis were used to study
      interneuronal connections in cerebellar vermis in awake rabbit. Crosscorrelation,
      or spike-triggering method, complemented the analysis of cross-intervals which
      estimated the neuronal interaction comparing spike sequences as point processes.
      Among 16 neuronal pairs recorded intra- or extracellularly 10 pairs were
      considered as interconnected. Inhibitory interconnections dominated. The
      inhibitory neuronal interconnections were revealed in pairs with complex spikes.
      Neurons which constituted pairs with reciprocal excitatory-inhibitory interaction
      fired only simple spikes. The variability and plasticity of common inputs to
      Purkinje cells were seemingly lower than those of direct connections which
      probably transmitted the output signals of Purkinje cells.

PMID- 9273792
TI  - [Changes in the oxidation-reduction potential of the rat brain during nembutal
      anesthesia].
AB  - The effect of the pentobarbital anaesthesia (40 mg/kg) on the potential of the
      cortical redox state (E) recorded by implanted platinum electrode was studied in
      male albino rats. A gradual decrease in the breathing frequency induced by
      pentobarbital was accompanied by a gradual reduction of the redox potential by 30
      80 mV. During the episodes with intermittent breathing there were additional
      decreases in redox potential by 30-80 mV against the background of which some
      rhythmical oscillations could be observed (the amplitude up to 25-30 mV, periods
      in 5-15 sec). The obtained data suggest that pentobarbital anaesthesia heavily
      changes the redox state of the brain tissue and shifts the balance to reducing
      state. Oscillations in redox potential against the background of breathing
      interruptions seem to be the typical glycolytic oscillations.

PMID- 9273793
TI  - [Serotonin simulates the neuronal effects of nociceptive sensitization in the
      snail].
AB  - Serotonin (5-HT) application (10 mcM) onto L-PPl1 neurons of the pleural ganglia
      of land snail Helix lucorum produced the synaptic facilitation of the neuronal
      response evoked by sensory stimulation. At the same time, it did not change the
      parameters of the neuronal membrane (resting potential and membrane
      excitability). In addition to synaptic facilitation, the higher 5-HT
      concentration (100 mcM) produced an increase in membrane excitability and a
      slight membrane depolarization. The 5-HT effects were modality-dependent: the
      duration of facilitation of the response evoked by tactile stimulation of the
      snail head was about 1 h while that of the response evoked by quinine application
      (0.3% solution) onto the snail lip was 2-3 h. The 5-HT effects were site
      specific: its application facilitated only the neuronal responses evoked by
      tactile stimulation of the snail head but not other body sites. The dynamics of
      the electrophysiological effects and the level of bound calcium were similar in L
      PPl1 neurons. The described neuronal effects resemble those observed after the
      nociceptive sensitization of these neurons. The data obtained suggest the 5-HT
      involvement in the mechanisms of short-term changes and consolidation of long
      term plasticity underlying the sensitization in Helix L-PPl1 neurons.

PMID- 9273794
TI  - [The properties of NADPHd-positive neurons in the brain of the snail].
AB  - Studies of NADPH-diaphorase (NADPHd) histochemistry in Helix brain indicate a
      number of discrete populations of putative NO-producing neurons in different
      ganglia. It has been shown that NADPHd-positive neurons (4 populations) have
      similar morphological, electrical, and plastic properties. These neurons are
      small (about 20 mcm), silent, with low threshold of excitability and low synaptic
      activity. They don't habituate to stimulation by impulses of depolarizing current
      and demonstrate low sensitivity to neurotransmitters. Serotonin, dopamine, and
      opioid peptides hyperpolarize, and glutamate, NMDA, and acetylcholine depolarize
      them. The evidence has been obtained that NO regulates the electrical and plastic
      properties of NADPHd-positive neurons in Helix brain and potentiates their
      sensitivity to glutamate. The properties of putative NO-producing Helix neurons
      have been compared with the known properties of vertebrate NO-producing neurons.
      The possible mechanisms are discussed of regulation by NO of the plastic
      properties of these neurons.

PMID- 9273795
TI  - [The effect of the serotonin level on the postsynaptically induced potentiation
      of neuronal responses in the snail].
AB  - The EPSP potentiation induced by the intracellular tetanization of a postsynaptic
      neuron was studied in the identified neurons of a terrestrial Helix lucorum
      snail. The high-frequency intracellular tetanization of the command neuron
      induced a two-phase long-term increase in the amplitude of synaptic responses.
      The role of 5-HT was studied in potentiation formation. The obtained evidence
      suggests that the presence of a certain 5-HT concentration in the extracellular
      fluid is necessary for the second phase formation while the first (short-term)
      phase is insensible to the 5-HT level in the CNS.

PMID- 9273796
TI  - [A comparison of serotonin- and dopaminergic neuronal systems in sexually mature
      and juvenile terrestrial mollusks of the genera Helix and Eobania].
AB  - The distribution of serotonin- (5-HT) and dopamine- (DA) containing neurons was
      studied in the brain of adult and juvenile (the first month of life) terrestrial
      molluscs Helix lucorum and Eobania vermiculata by means of glyoxylic acid
      fluorescent technique and neurotoxin 5,7-DiHT labelling. The majority of 5-HT
      containing cells were grouped in clusters in the pedal ganglia (the median number
      of cells in a cluster was 213 in Eobania and 155 in Helix). Some cells were
      described in the cerebral ganglia, visceral and right parietal ganglia. DA
      containing neurons were found in the buccal ganglia, cerebral ganglia (there were
      6-8 large dorsal cells and about 80 small ventral cells) and pedal ganglia (the
      median number of cells was 36 in Helix and 12 in Eobania). In juvenile animals of
      both species the number and distribution of clusters with monoaminergic cells
      resembled that of the adults. In the juvenile pedal ganglia the number of 5-HT
      containing cells was about one fourth of that in adult snails. The number of DA
      containing cells in juveniles was the same as in adults in both species. In
      juvenile snails of both species one big and two medium-sized 5-HT-containing
      cells were found at the dorsal surface of the cerebral ganglia. Such cells were
      not revealed in adults. The finding suggests that these cells can change the
      transmitter phenotype or be transient.

PMID- 9273797
TI  - [The effect of damage to the locus coeruleus or the raphe nuclei on circadian
      rhythms in rats in open-field testing].
AB  - The electrolytic lesions of raphe or locus coeruleus (I = 1-1.5 mA, 20 sec, with
      a change in polarity) produce a destabilization in the circadian rhythms of the
      active searching behaviour (tested in the "open field") in rats kept under
      conditions of natural illumination in the period of the winter or summer
      solstice. The daily or circadian components are substituted, respectively, for
      the ultra- or infradian rhythms. If the animals are kept for 10 days under 24-h
      light or dark conditions, the serotoninergic or noradrenergic deficit delays the
      formation of free-running rhythms.

PMID- 9273798
TI  - [Emotional stress and sleep: a study of adrenalectomized rats].
AB  - Polygraphic recordings were performed during 12-h dark period in 18
      adrenalectomized rats with implanted electrodes for ECoG and EMG under normal
      conditions and following 1-h immobilization period. The exposure of rats to
      emotional immobilization stress evoked a highly significant increase in sleep
      which was especially pronounced for the slow wave sleep (about 40% above the
      control value). The immobilization effect was completely abolished by preliminary
      treatment with dexametazone (1 mg/kg subcutaneously). Thus, adrenal steroids are
      involved into the interrelation between the emotional stress and sleep as a link
      in a negative feedback loop.

PMID- 9273799
TI  - [Sexual behavior and alpha-2 adrenoreceptors in the neocortex of male rats after
      castration and testosterone administration].
AB  - Castration of male rats inhibited their sexual behaviour and increased the
      density of the alpha-2 adrenergic receptors in the brain cortex. Treatment of
      castrated or intact males with testosterone activated their sexual behaviour and
      decreased the receptor density in the brain cortex. The obtained evidence testify
      to the involvement of the brain alpha-2 adrenergic receptors in the effect of
      testosterone on male sexual behaviour.

PMID- 9273800
TI  - [The effect of the administration of beta-amyloid peptide fragment (25-35) on
      behavior in rats].

PMID- 9273801
TI  - [Long-term effects of febrile seizures in early ontogeny on learning processes
      and memory in adult rats].

PMID- 9273802
TI  - [The physiology of activity (on the centenary of the birth of N. A. Bernstein)].

PMID- 9273803
TI  - [The possibilities for the principle of complementarity in psychophysiology].

PMID- 9273804
TI  - [Mammography].
AB  - Today mammography represents the only imaging modality that decreases with the
      help of screening programs the mortality rate of breast cancer patients. This
      becomes increasingly necessary because already every tenth woman in Austria will
      get this tumor during her lifetime. There is conclusive evidence that the
      patients chance for survival depends on the clinical status of breast cancer at
      the time of diagnosis. Therefore every woman should undergo a yearly mammogram
      starting at 40 years of age. If sensitivity and specificity of mammography is
      under consideration one must differentiate its role during a screening program
      versus the situation of a symptomatic patient.

PMID- 9273805
TI  - [Ultrasound mammography].
AB  - The development of high resolution technology ultrasound allows not only a simple
      differentiation between cystic and solid lesions. Palpable tumors and subclinical
      lesions can be detected and characterized with a high degree of accuracy. The
      specific sonographic appearances of the most common entities are described. The
      diagnostic criteria for the differentiation have been developed over many years.
      There is no single parameter which allows the differentiation of all lesions, and
      a number of criteria must be considered.

PMID- 9273806
TI  - [MR mammography: current status and indications].
AB  - Several reports in the literature have demonstrated a promising role for MR
      imaging when used as an adjunct to mammography for the detection and diagnosis of
      breast cancer. There are many technical factors that must be considered,
      including dynamic imaging with subtraction, high resolution and fat suppression.
      Proven indications for MR mammography include patients suspicious of having
      cancer recurrence after breast conservation treatment and patients suspicious of
      having breast implant rupture. Potential clinical applications include
      differentiating benign from malignant lesions, detecting cancer when results of
      conventional imaging are equivocal, staging newly diagnosed breast cancer,
      detecting occult cancer in patients presenting with axillary node metastasis,
      determining chemotherapy induced tumor response, detecting residual tumor after
      incomplete surgical excision. Several investigators have demonstrated that MR
      imaging can provide extremely high sensitivity for detection of breast cancer.
      There are pitfalls, however, secondary to false positive and false negative
      contrast enhancement. Awareness of the strengths and limitations of MR imaging of
      the breast will facilitate integration of this technique into the work-up of
      patients with suspicious breast lesions.

PMID- 9273807
TI  - [Possible uses of positron emission tomography in breast carcinoma].
AB  - Increased glucose metabolism by malignant tissue can be visualized with positron
      emission tomography (PET), using the radiolabeled glucose analogue F-18
      fluorodeoxyglucose (FDG). Depending on the criteria of image interpretation FDG
      PET allows detection of breast cancer with a sensitivity of 68% to 94% and a
      specificity of 84% to 97%. However, sensitivity to visualize small tumors (< 1
      cm) is limited. Positron emission tomography demonstrates tumor involvement of
      regional lymph nodes with high accuracy, predominantly in patients with advanced
      breast cancer. The sensitivity for the detection of axillary lymph node
      metastases was 79% with a corresponding specificity of 96%. Lymph node metastases
      could not be identified in four of six patients with small primary breast cancer
      (stage pT1), resulting in a sensitivity of only 33% in these patients. By
      visualizing primary tumors and metastases in one imaging procedure, PET imaging
      may allow the effective staging of breast cancer patients. Further studies are
      needed to define the role of scintigraphic techniques for the diagnostic work-up
      in patients.

PMID- 9273808
TI  - [PET scan in general practice for diagnosis of breast carcinoma].
AB  - The value of whole body positron emission tomography using 18F-fluoro-deoxy
      glucose (18FDG) in primary work-up and follow-up was evaluated retrospectively in
      104 patients with primary or metastatic breast cancer. Compared to other imaging
      methods, FDG-PET sensitivity was superior to sonography, CT or MRT. Another
      advantage is the possibility of whole body imaging and the earlier detection of
      lymph node metastasis due to the recognition of functional metabolic changes
      compared to structural changes found with conventional imaging methods.

PMID- 9273809
TI  - [Probe-guided surgery of colorectal carcinoma].
AB  - Anti-CEA-scintigraphy turned out very reliable in detecting primary and recurrent
      colorectal cancer, its overall accuracy being more than 90 p.c. The
      intraoperative application of this technology should provide similar results when
      focussing at extrahepatic tumor deposits, for example in lymph nodes, thus
      allowing accurate staging of the underlying disease. To test this hypothesis we
      lauched the following feasibility-study the results of which are compared to
      those reported in the recent literature. We investigated 20 patients-six with
      rectum-, 14 with colon cancer, 24 hours before surgery they were intravenously
      given 1 ml of an fab-fragment-antibody to CEA, labeled with 25mCi of 99mTc (CEA
      Scan). During surgery the radioactivity in lymph glands regionary for the tumors
      was measured and compared to the-much lower-activity in healthy nodes. For this
      we used a scintillation-probe (C-Trak). All lymph nodes of interest were-then
      excised and submitted to frozen section pathology. In 7/20 cases scintimetry led
      to an up-staging of the disease. In addition we found metastatic spread to lymph
      nodes that were basically not regionary for the primary tumor. Our results are
      confirmed by those of other investigators. Scintimetry can precisely identify
      even very small tumor deposits. So it leads to accurate staging when surgery is
      still on-going. In a next step the concept of sentinel-node-diagnosis, which is
      right now being clinically evaluated, may be applied is colorectal surgical
      oncology.

PMID- 9273810
TI  - [Use of a gamma probe for intraoperative localization of parathyroid adenomas
      with Tc-99m-tetrofosmin and Tc-99m-sestamibi].
AB  - Especially ectopic adenomas may be problematic in intraoperative localization
      despite preoperative imaging resulting in a longer operating time and more
      extensive surgical preparation. The aim of our study was to evaluate the
      possibility of intraoperative scintimetric detection of parathyroid adenomas with
      cationic, Tc-99m labelled tracers for its usefulness in ectopic adenomas. 12
      women with biochemically confirmed hyperparathyroidism were included in our
      study. After injection of 370 MBq Tc-99m Tetrofosmin respectively Sestamibi,
      preoperative scintigraphy (double phase study and SPECT) was performed and T/NT
      ratios were evaluated for early, delayed and SPECT images. Surgery was performed
      using a hand-held gamma probe after preoperative injection of 555-925 MBq Tc-99m
      Tetrofosmin or Sestamibi. Count rates (cts/10 sec) were measured and used for
      calculating in situ- and ex situ-T/NT ratios. In 9 out of 12 patients, adenoma
      could be detected on static images. Three cases could only be detected with
      SPECT. 11 of 12 parathyroid adenomas could be confirmed intraoperatively.
      Intraoperative localization of parathyroid adenoma with Tc-99m-labelled cationic
      complexes and a gamma probe is possible and may be useful in case of ectopic
      adenoma by influencing surgical approach and operating time.

PMID- 9273811
TI  - [Selective regional lymphadenectomy in malignant melanoma using a gamma probe].
AB  - The accurate excision of the first tumour draining lymph node (sentinel lymph
      node SLN) can prevent extended surgery intervention in many patients with
      malignant melanoma. The aim of our study was to test the practicability of the
      SLN dissection using a gamma probe. In a total of 52 patients, mostly with high
      risk melanoma, a selective lymph node dissection was performed. We injected
      intracutuneously about 50 MBq Tc-99m colloid around the tumour or scar followed
      by dynamic and late static imaging. The site of SLN was localized with a gamma
      probe and marked on the skin. This was followed by the dissection of the SLN
      using the gamma probe. In 51 of 52 patients the SLN could be found
      intraoperatively using the gamma probe. The SLN contained microscopic metastases
      in 13 patients (24%). The rate of positive SLN was 40% in patients with high-risk
      melanoma (Breslow thickness more than 1.5 mm). In case of positive SLN a second
      surgical intervention with radical lymph node dissection was followed. We
      conclude that dynamic lymphscintigraphy and the selective lymph node dissection
      using the gamma probe is a simple and minimally invasive method which can improve
      the survival probability in patients with micrometastases.

PMID- 9273813
TI  - The Scandinavian opinion on assessment of female urinary incontinence.
      Proceedings of a meeting. Copenhagen, Denmark, 1995.

PMID- 9273814
TI  - European Magnetic Resonance Forum Proceedings. New developments in contrast agent
      research 5th special topic seminar on magnetic resonance contrast agents. Santa
      Margherita Ligure, Italy, 5-7 June 1996.

PMID- 9273812
TI  - [Pre- and intraoperative localization of neuroendocrine tumors].
AB  - Previous studies of the intraoperative use of a hand-held gamma probe to localize
      metastases and primary tumors of colorectal cancer have shown improved assessment
      of tumor spread and changes in surgical management based on added information
      gained by radioimmunoguided surgery. Following the injection of 180 MBq [111In
      DTPA-D-Phe1]-pentetreotide and/or 500 MBq 99mTc-dimercaptosuccinic acid (both for
      dual-radionuclide scintigraphy) preoperative somatostatin receptor imaging [11
      patients with GEP tumors] and dual-radionuclide scintigraphy. (8 patients with
      relapsing medullary thyroid carcinomas) was performed. One patient with a
      metastasizing pheochromocytoma underwent 123]-MIBg scintigraphy. Results were
      combined with the information obtained from conventional imaging modalities.
      Intraoperative radiodetection was performed 24 hours after administration of
      [111In-DTPA-D-Phe1]-pentetreotide or 4 hours following the injection of
      99mTc(V)DMSA using a hand-held gamma probe (Tec Probe 2000. Stratec, FRG).
      Intraoperative gamma counting localized 39 somatostatin receptor positive lesions
      of GEP tumors whereas preoperative receptor imaging visualized 81%, surgical
      palpation 41% and radiological imaging modalities localized only 31%. In 8
      patients with recurrent medullary thyroid carcinoma the surgeon was successful in
      localizing and removing 18 tumor lesions by the help of the gamma probe. Dual
      radionuclide scintigraphy revealed 77% (Octreoscan 5/18; 99mTc-V-DMSA 9/18),
      surgical palpation 55% and conventional imaging methods (CT, sonography) only 38%
      of all lesions detected intraoperatively by the hand-held gamma probe. In
      summary, this preliminary data show that intraoperative hand-held gamma probe
      detection of microscopic and occult endocrine tumors is feasible and more
      sensitive than external scintigraphy and conventional imaging.

PMID- 9273815
TI  - Proceedings of the 1st International Rushmore Conference on Mechanisms in the
      Pathogenesis of Enteric Diseases. Rapid City, South Dakota, September 28-30,
      1995.

PMID- 9273816
TI  - Old dogs: new tricks, old tricks, or no tricks.

PMID- 9273817
TI  - A recommendation on recommendations.

PMID- 9273818
TI  - The four doctors.

PMID- 9273819
TI  - Teleradiology and a specialty at risk.

PMID- 9273820
TI  - Medical abortion is not just a medical issue.

PMID- 9273821
TI  - Pathological characterization of astrocytic hyaline inclusions in familial
      amyotrophic lateral sclerosis.
AB  - To clarify the pathological characteristics of astrocytic hyaline inclusions (Ast
      HIs) in patients with familial amyotrophic lateral sclerosis (FALS) with neuronal
      Lewy-body-like hyaline inclusions (LBHIs), eight autopsies on members of four
      different families, including two long-term surviving patients with clinical
      courses of over 10 years, were analyzed. Ast-HIs were found only in the two long
      term surviving patients who belonged to different families and to different
      races. Ast-HIs were ultrastructurally composed of 15- to 25-nm granule-coated
      fibrils that had immunoreactivities to superoxide dismutase 1 (SOD1) and
      ubiquitin. Approximately 50% of the Ast-HIs expressed alpha B-crystallin,
      metallothionein, glutamine synthetase, and tubulin (alpha and beta) at various
      intensities. Some Ast-HIs reacted with antibodies to tau protein, S-100 protein,
      and heat shock protein 27. The Ast-HIs were not stained for glial fibrillary
      acidic protein. Our results suggest a cooperative role of superoxide dismutase 1,
      ubiquitin, and cytoskeletal proteins in the formation of granule-coated fibrils
      (namely, Ast-HIs) and provide evidence that Ast-HIs are formed in certain long
      surviving familial amyotrophic lateral sclerosis patients with neuronal Lewy-body
      like hyaline inclusions.

PMID- 9273823
TI  - Visions of the future: the analyst's expectations and their impact on the
      analytic process.

PMID- 9273822
TI  - Extrasynaptic location of laminin beta 2 chain in developing and adult human
      skeletal muscle.
AB  - We have investigated the distribution of the laminin beta 2 chain (previously s
      laminin) in human fetal and adult skeletal muscle and compared it to the
      distribution of laminin beta 1. Immunoblotting and transfection assays were used
      to characterize a panel of monoclonal and polyclonal antibodies to the laminin
      beta 2 chain. We found that laminin beta 1 chain was detected at all times during
      development from 10 weeks of gestation. Laminin beta 2 chain was first detected
      in 15 to 22-week-old fetal skeletal muscle as distinct focal immunoreactivity in
      the sarcolemmal basement membrane area of some myofibers. In the adult skeletal
      muscle, laminin beta 2 chain immunoreactivity was found along the entire
      perimeter of each of the individual myofibers in a large series of different
      muscles studied. Laminin beta 2 chain was similarly found in the skeletal muscle
      basement membranes in patients with Duchenne and Becker muscular dystrophy.
      Immunoaffinity chromatography of muscle extracts with a monoclonal antibody to
      the laminin alpha 2 chain followed by immunoblotting with various antibodies to
      the beta 2 chain demonstrated the presence of the laminin-4 (alpha 2-beta 2-gamma
      1) isoform. Together the present results demonstrate a prominent extrasynaptic
      localization of laminin beta 2 in the human muscle, suggesting that it may have
      an important function in the sarcolemmal basement membrane.

PMID- 9273824
TI  - Effect of angiotensin-converting enzyme inhibitors on the progression of
      nondiabetic renal disease: a meta-analysis of randomized trials. Angiotensin
      Converting-Enzyme Inhibition and Progressive Renal Disease Study Group.
AB  - BACKGROUND: The effect of angiotensin-converting enzyme (ACE) inhibitors in
      slowing the decline in renal function in nondiabetic renal disease varies among
      studies. PURPOSE: To use meta-analysis to assess the effect of ACE inhibitors on
      the development of end-stage renal disease caused by factors other than diabetes.
      DATA SOURCES: The English-language medical literature, identified by a MEDLINE
      search and unpublished studies. STUDY SELECTION: All randomized studies that
      compared ACE inhibitors with other antihypertensive agents and had at least 1
      year of planned follow-up were selected. Studies of diabetic renal disease and
      renal transplants were excluded. A total of 1594 patients in 10 studies was
      included. DATA EXTRACTION: Data on end-stage renal disease, death, drop out, and
      blood pressure were extracted. Study investigators confirmed results and provided
      additional data. DATA SYNTHESIS: Among 806 patients receiving ACE inhibitors, 52
      (6.4%) developed end-stage renal disease and 17 (2.1%) died; in the 788 controls,
      the respective values were 72 (9.1%) and 12 (1.5%). The pooled relative risks
      were 0.70 (95% CI, 0.51 to 0.97) for end-stage renal disease and 1.24 (CI, 0.55
      to 2.83) for death; the studies were not significantly heterogeneous. The
      decreases in weighted mean systolic and diastolic blood pressures during follow
      up were 4.9 and 1.2 mm Hg greater, respectively, in the patients who received ACE
      inhibitors. CONCLUSIONS: Angiotensin-converting enzyme inhibitors are more
      effective than other antihypertensive agents in reducing the development of end
      stage nondiabetic renal disease, and they do not increase mortality. It could not
      be determined whether this beneficial effect is due to the greater decline in
      blood pressure or to other effects of ACE inhibition.

PMID- 9273825
TI  - ACE gene polymorphism as a risk factor for ischemic cerebrovascular disease.
AB  - BACKGROUND: Researchers have suggested that the deletional allele of the ACE
      (angiotensin-converting enzyme) gene insertion-deletion polymorphism is a potent
      risk factor for myocardial infarction. This association could not be confirmed in
      the Copenhagen City Heart Study, in which 10,150 persons were studied. The ACE
      gene polymorphism has also recently been suggested as a potent risk factor for
      ischemic cerebrovascular disease. OBJECTIVE: To investigate the association
      between ACE gene polymorphism and ischemic cerebrovascular disease. DESIGN: Two
      case-referent studies and a cross-sectional study. SETTING: University hospital
      in Copenhagen, Denmark. PARTICIPANTS: Case-referent study 1: 35 women and 38 men
      who developed ischemic cerebrovascular disease before 50 years of age compared
      with 1454 women and 1737 men from a general population sample. Case-referent
      study 2: 82 women and 137 men with ischemic cerebrovascular disease and carotid
      stenosis greater than 40% compared with 4273 women and 3091 men from the general
      population sample. Cross-sectional study of the general population sample: 67
      women and 93 men with ischemic cerebrovascular disease compared with 4077 women
      and 3156 men without such disease. MEASUREMENTS: Genotype; age; body mass index;
      smoking habits; levels of lipids, lipoproteins, apolipoproteins, and fibrinogen;
      and diagnosis of hypertension, diabetes mellitus, and ischemic cerebrovascular
      disease. RESULTS: Odds ratios for ischemic cerebrovascular disease by ACE
      genotype classes were not significantly different from 1.0 in women or men in any
      of the three studies, separately or combined. In a logistic regression analysis
      that controlled for age and conventional cardiovascular risk factors, odds ratios
      in either sex still did not significantly differ from 1.0 in any study,
      separately or combined. CONCLUSION: In two case-referent studies, a cross
      sectional study, and the three studies combined, no statistically significant
      difference was found in the development of ischemic cerebrovascular disease
      between genotype classes of the ACE gene polymorphism in women or men.

PMID- 9273826
TI  - Risk factors for methotrexate-induced lung injury in patients with rheumatoid
      arthritis. A multicenter, case-control study. Methotrexate-Lung Study Group.
AB  - BACKGROUND: Toxicity limits the use of methotrexate. OBJECTIVE: To identify risk
      factors for methotrexate-induced lung injury in patients with rheumatoid
      arthritis. DESIGN: Case-control study. SETTING: One private and five academic
      rheumatology practices. PARTICIPANTS: Methotrexate recipients with rheumatoid
      arthritis with and without lung injury. MEASUREMENTS: Potential risk factors
      examined were sociodemographic and lifestyle characteristics, medical history,
      clinical and ancillary features and treatment of rheumatoid arthritis before
      methotrexate therapy, and characteristics of methotrexate therapy. Cases of lung
      injury were defined according to the modified criteria of Searles and McKendry.
      RESULTS: Ninety-four percent of the study participants were white, and 67% were
      women. Case-patients (n = 29) were older than controls (n = 82) (61.5 compared
      with 54.5 years of age). The strongest predictors of lung injury, after
      adjustment for other variables, were older age (odds ratio [OR], 5.1 [95% CI, 1.2
      to 21.1]), diabetes (OR, 35.6 [CI, 1.3 to infinity]), rheumatoid pleuropulmonary
      involvement (OR, 7.1 [CI, 1.1 to 45.4]), previous use of disease-modifying
      antirheumatic drugs (OR, 5.6 [CI, 1.2 to 27.0]), and hypoalbuminemia (OR, 19.5
      [CI, 3.5 to 109.7]). Previous use of disease-modifying antirheumatic drugs and
      hypoalbuminemia had very large attributable risks. CONCLUSION: Knowledge of the
      risk factors that predispose patients with rheumatoid arthritis to the toxic
      effects of methotrexate on the lung may provide a rationale for monitoring high
      risk patients and may facilitate their management.

PMID- 9273827
TI  - Blood transfusion and non-Hodgkin lymphoma: lack of association.
AB  - BACKGROUND: Non-Hodgkin lymphoma is the seventh most commonly diagnosed malignant
      condition worldwide, and its incidence has increased markedly in recent decades.
      Blood transfusions have been implicated as a possible risk factor for non-Hodgkin
      lymphoma. OBJECTIVE: To determine whether blood transfusions are associated with
      an elevated risk for non-Hodgkin lymphoma. DESIGN: Population-based, nested case
      control study. SETTING: Nationwide cohort in Sweden. PATIENTS: 361 patients with
      non-Hodgkin lymphoma and 705 matched controls, nested within a population-based
      cohort of 96795 patients at risk for blood transfusion between 1970 and 1983.
      Prospectively collected information on exposure was retrieved from computerized
      transfusion registries. MEASUREMENTS: Odds ratios obtained from conditional
      logistic regression models were used as measures of relative risks. RESULTS: No
      association was found between blood transfusions and the risk for non-Hodgkin
      lymphoma when patients who had received transfusions were compared with patients
      who had not received transfusions (odds ratio, 0.93 [95% CI, 0.71 to 1.23]). A
      reduction in risk was seen among persons who received transfusion of blood
      without leukocyte depletion (odds ratio, 0.72 [CI, 0.53 to 0.97]). Risk was not
      related to number of transfusions, and no interaction was seen with latency after
      transfusion. CONCLUSION: The findings in this study do not support previous
      observations of an association between blood transfusions and the risk for non
      Hodgkin lymphoma.

PMID- 9273828
TI  - Differences in the effect of cigarette smoking on endothelial function in chinese
      and white adults.
AB  - BACKGROUND: The prevalence of coronary artery disease in southern China is
      approximately one fifth that in "westernized" countries, even though
      approximately 70% of Chinese men smoke cigarettes and Chinese women have
      substantial passive exposure to cigarette smoke. OBJECTIVES: Endothelial
      dysfunction is an early event in atherosclerosis and occurs in young white active
      and passive smokers; we compared endothelial physiology in healthy young Chinese
      and white smokers and nonsmokers. PATIENTS: 144 healthy adults who were 16 to 45
      years of age: 72 Chinese persons in a village in southern China and 72 white
      persons in Australia and England who were matched for exposure to cigarette
      smoke. Each ethnic group comprised 36 controls (lifelong nonsmokers with no
      regular exposure to cigarette smoke; 16 men and 20 women) and 36 active or
      passive smokers (15 men and 21 women). MEASUREMENTS: Arterial endothelial
      function was tested with high-resolution external vascular ultrasonography, and
      brachial artery diameter was measured at rest, after flow increase (which causes
      endothelium-dependent dilatation), and after administration of sublingual
      nitroglycerin (an endothelium-independent dilator). RESULTS: Endothelium
      dependent dilatation was similar in Chinese (7.9%) and white (8.4%) nonsmokers (P
      > 0.2). Among white persons, endothelium-dependent dilatation was lower in active
      or passive smokers (3.9%) than in nonsmokers (8.4%) (P < 0.001). Among Chinese
      persons, dilatation was not significantly lower in active or passive smokers
      (7.3%) than in nonsmokers (7.9%) (P > 0.2). Dilatation was higher in Chinese
      active or passive smokers (7.3%) than in white active or passive smokers (3.9%)
      (P < 0.001). Dilatation responses to nitroglycerin were similar in all groups (P
      = 0.17). CONCLUSION: Young Chinese adults have less evidence of arterial
      endothelial dysfunction than young white adults with similar direct or indirect
      exposure to cigarette smoke.

PMID- 9273829
TI  - Alcohol metabolism in Asian-American men with genetic polymorphisms of aldehyde
      dehydrogenase.
AB  - BACKGROUND: About half of certain Asians have a deficiency of the low-Km aldehyde
      dehydrogenase (ALDH2) isoenzyme. This deficiency results from inheritance of a
      mutant ALDH2*2 allele. OBJECTIVE: To determine whether Asian Americans with
      ALDH2*2 alleles differ from Asian Americans without this mutation in terms of
      blood levels of alcohol and acetaldehyde after ingestion of a moderate amount of
      alcohol. DESIGN: Double-blind, crossover study. SETTING: Private research
      institute. PARTICIPANTS: 35 healthy Asian-American men. Three men who became ill
      after alcohol ingestion and one who had outlying data were excluded.
      INTERVENTION: Alcoholic beverage, containing 0.56 g of alcohol per kg of body
      weight, or placebo beverage, containing 3 mL of alcohol, given orally on separate
      occasions. MEASUREMENTS: Blood levels of alcohol and acetaldehyde measured before
      and several times after ingestion of the alcoholic or placebo beverage. RESULTS:
      Participants with ALDH2*2 alleles had significantly higher blood acetaldehyde
      levels after ingesting alcoholic and placebo beverages than did participants with
      ALDH2*1 alleles, despite similar blood alcohol concentrations. CONCLUSIONS: Blood
      acetaldehyde levels rather than blood alcohol concentration may mediate enhanced
      alcohol sensitivity among Asians with ALDH2*2 alleles.

PMID- 9273830
TI  - Formulating questions and locating primary studies for inclusion in systematic
      reviews.
AB  - Much time and effort are spent on designing primary research studies. Similar
      care must be given to planning systematic reviews. The review should be based on
      an important, well-focused question that is relevant to patient care. By
      formulating the question properly, the criteria that primary studies must meet to
      be included in the review become clear. These criteria, which comprise the types
      of persons involved, exposure, control group, outcomes, and study designs of
      interest, can then be refined so that they are clinically relevant, sensible, and
      workable. Inclusion criteria that are too narrow will limit the amount of data in
      the review, thereby increasing the risk for chance results and making the review
      less useful for the reader. Reviews should include studies whose designs offer
      the least biased answer to the question being asked. To maximize available data
      and reduce the risk for bias, as many relevant studies as possible need to be
      identified, regardless of publication status or language. Multiple overlapping
      search strategies should therefore be used and must be carefully planned.
      Strategies include searching the many electronic databases available (after
      careful consideration of which terms to enter), manually searching journals and
      conference proceedings, searching bibliographies of articles, searching existing
      registers of studies, and contacting companies or researchers. The time taken to
      formulate the question adequately and develop appropriate searches will increase
      the chance of producing a high-quality, meaningful review.

PMID- 9273831
TI  - Encouraging patients to become more physically active: the physician's role.

PMID- 9273833
TI  - Vaccines for tuberculosis: the glass remains half empty.

PMID- 9273832
TI  - Ethnic variation as a key to the biology of human disease.

PMID- 9273834
TI  - Survival.

PMID- 9273835
TI  - Nonalcoholic steatohepatitis.

PMID- 9273836
TI  - Nonalcoholic steatohepatitis.

PMID- 9273837
TI  - Nonalcoholic steatohepatitis.

PMID- 9273838
TI  - Nonalcoholic steatohepatitis.

PMID- 9273839
TI  - Nonalcoholic steatohepatitis.

PMID- 9273840
TI  - Cytomegalovirus and death in liver transplantation.

PMID- 9273841
TI  - [Renal cell adenocarcinomas. Report of 64 cases].
AB  - The authors report 64 renal cell carcinomas observed in 64 patients over a period
      of 14 years (1982-1995). The mean age was 58 years (range: 20 to 80 years). Male
      involvement was observed in 34 cases (53%). The clinical symptoms were
      nonspecific, consisting of haematuria (26 cases), back pain (33 cases) and tumour
      (8 cases). Twenty patients presented with paraneoplastic syndromes and 4
      presented with metastases. The tumour was an incidental finding in 6 cases. Fifty
      two patients were treated by radical nephrectomy and two by partial nephrectomy.
      The tumour was associated with venous involvement in 2 cases, lymphatic
      involvement in 4 cases and distant metastases in 2 cases. The overall 5-year
      survival was 37% with a poor prognosis in the case of lymph node involvement or
      metastases and in the case of secondary local recurrence (4 cases) or distant
      metastases (2 cases).

PMID- 9273842
TI  - [Renal oncocytoma. Report of 13 cases].
AB  - We report 13 cases of renal oncocytoma. Urinary symptoms occurred in only 3
      cases. The patient's age ranged from 41 to 74 years with an average of 62.3
      years. The mean tumor diameter was 5.6 cm (range: 1.5-14). Diagnostic features of
      ultrasonography, CT scan and, in some instances, angiography were suggestive of
      renal oncocytoma in 2 patients, but never affirmative, 4 patients were treated by
      partial nephrectomy. No local or metastatic recurrence was observed with a mean
      follow-up of 30.8 months, ranging from 6 to 96 months. We assume that the term
      renal oncocytoma should be restricted to tumors exclusively composed of regular
      oncocytic cells with an eosinophilic granular mitochondria-rich cytoplasm and an
      absence of malignant potential. Diagnostic imaging characteristics may sometimes
      suggest the diagnosis of renal oncocytoma, but cannot eliminate the main
      differential diagnosis, i.e. granular renal cell adenocarcinoma. When the tumor
      is small and unifocal, nephron sparing surgery may be considered. Whether or not
      the diagnosis has been confirmed by fine needle aspiration, conservative surgery
      must be controlled by intraoperative frozen sections of the tumor and surgical
      margins.

PMID- 9273844
TI  - [Value of nephron preservation in conservative surgery of renal tumors].
AB  - The increasing use of abdominal ultrasonography and computed tomography results
      in the increasingly early diagnosis of subclinical renal tumours. These
      asymptomatic tumours can sometimes be treated conservatively. This technique
      raises the problem of the multifocal nature of renal tumours In order to assess
      the real benefit of nephron-sparing surgery in relation to the risk of
      recurrence, this study evaluates the repercussions of exclusive tumour resection
      on the nephron number. From 1990 to 1995, 28 patients underwent partial
      nephrectomy for suspected renal cell carcinoma. Computed tomography was use to
      estimate the volume and therefore the weight of the kidney and the tumour: weight
      (g) = volume (mL) = length x width x height/2. The mean age of the patients was
      59.1 years. The contralateral kidney was normal in 20 patients (group 1) and the
      tumour affected a solitary kidney in 8 patients (group 2). The initial serum
      creatinine level was normal (between 78 and 96) in all patients. The mean weight
      of the tumour was 16.1 g (13.6 g for group 1 and 22.3 g for group 2), and
      corresponded to 3.84% of the total kidney weight in group 1 and 9.73% in group 2.
      1,400,000 nephrons were preserved in group 1 versus 900,000 nephrons in group 2,
      equivalent to a glomerular filtration rate of 89 mL/min and 58 mL/min,
      respectively. Partial nephrectomy therefore constitutes a real nephron-sparing
      technique. It allows sparing of a sufficient number of nephrons to ensure normal
      renal function and, most importantly, allows the possibility of subsequent
      partial surgery in view of the potential risk of multifocal tumours.

PMID- 9273845
TI  - Applying research.

PMID- 9273846
TI  - Protein engineering from a bioindustrial point of view.
AB  - Work with proteins, particularly enzymes, is a rapidly growing segment of the
      biotechnology industry. Directed evolution promises to become an increasingly
      important strategy in their development as it allows one to sidestep some of the
      difficult questions relating the structural and functional properties of such
      proteins to their industrial utility. It is also clear, however, that greater
      understanding of how to engineer certain basic enzyme properties, such as
      stability, activity, and surface properties, is beginning to emerge, and this
      understanding will make rational design more efficient. To engineer a
      commercially useful protein many properties need to be changed, and frequently
      these changes are interdependent. Recent protein engineering studies on protease,
      amylase, lipase and cellulase illustrate some of the progress in this area.

PMID- 9273843
TI  - [Renal oncocytoma: nephrectomy or tumorectomy? Description of five cases and
      review of the literature].
AB  - Oncocytoma is an uncommon benign tumor of the kidney. Its incidence represents 3
      to 10% of all solid renal masses. This diagnosis, seldom recognized before the
      operation, is often revealed by anatomo-histological examination. Surgical
      treatment of a small tumor, ever the most benign, can be limited to enucleation
      or partial nephrectomy to spare renal parenchyma. When a small, solid and well
      confined renal mass is discovered, the diagnosis of oncocytoma must be considered
      and the usual investigations (abdominal ultrasound, CT-scan...) must be completed
      by renal angiography to obtain as much information as possible in support of the
      diagnosis of oncocytoma, justifying nephron-sparing surgery.

PMID- 9273847
TI  - Recombinant proteins from transgenic plants.
AB  - Transgenic plants can express a wide variety of foreign genes and offer the
      opportunity of large-scale protein production in agricultural systems. The
      recombinant protein can serve both ex situ and in situ purposes. Due to
      significant progress in plant molecular biology, many different plant species can
      now be transformed and are even capable of producing very complex proteins such
      as antibodies or vaccines. Furthermore, recombinant proteins can mediate
      resistance against microbial pathogens, such as fungi or viruses, or protect
      transgenic plants from insect pests.

PMID- 9273849
TI  - Protein engineering.

PMID- 9273850
TI  - Lipids Social order among lipids in membranes.

PMID- 9273848
TI  - Protein folding and intermediates.
AB  - With the exception of the discovery of the rate of formation of the earliest
      intermediates, there have been no major conceptual leaps in our understanding of
      protein folding reactions over the past two years. Rather, this period has seen
      an extension of two established techniques: first, mutational analysis combined
      with a kinetic definition of the energy landscape of the reaction; and second,
      the use of hydrogen/deuterium exchange of backbone amide groups combined with
      NMR. Owing to the application of these methods to a wider range of proteins, it
      is now possible to draw some general conclusions about the physical processes
      that direct a protein to its native fold.

PMID- 9273851
TI  - Engineering and design Screening, selection and design: standing at the
      crossroads in three dimensions.

PMID- 9273852
TI  - Web alert Engineering and design Lipids Membrane proteins.

PMID- 9273853
TI  - The callosal connections of the hierarchically organized somatosensory areas of
      primates.

PMID- 9273856
TI  - Predictive factors of callosotomy in drug-resistant epileptic patients with a
      long follow-up.
AB  - Some possible factors to predict outcome after callosotomy were investigated in a
      personal series composed of 36 patients. Twenty-seven of them were submitted to
      anterior callosotomy, 1 to posterior callosotomy and the remaining 8 patients to
      two stage complete division of corpus callosum. All factors, either positive or
      negative, do not appear completely reliable; they can be envisaged only in
      relative terms and do not seem to be relevant to make surgical decision or to
      discard surgery. In author's series, dealing specifically with drop-attacks, it
      clearly appeared that abrupt falls to the ground unpreceded by other epileptic
      features did definitely better. This was the only statistically significant
      datum.

PMID- 9273855
TI  - The role of corpus callosum in experimental epileptogenesis. A brief survey of
      literature.
AB  - The authors briefly summarize the experimental papers dealing with the role of
      corpus callosum in experimental epileptogenesis published over more than half a
      century. On the whole, the experimental work concerns more electro
      encephalographic findings than epileptic manifestations in animals. The papers
      taken into account are classified in two main groups: I) positive findings
      supporting the efficacy of callosotomy in preventing generalization of initially
      localized seizures. II) papers failing to demonstrate any positive effect of
      commissurotomy on the generalization of discharges. On these grounds,
      experimental studies lack of homogeneity and cannot constitute a reliable basis
      for making surgical decision in clinical practice. However some remarks of
      practical use can be derived: a) the usefulness of the corpus callosum division
      for the management of secondarily generalized epilepsies appears to be
      sufficiently demonstrated in most studies; b) then is also evidence that the
      corpus callosum conveys inhibitory and/or suppressive stimuli as well, the
      practical value of which is still to be established; d) the corpus callosum is
      the most important but not the only anatomic structure for spreading seizures.
      Anterior and posterior commissures, thalamus, tegmentum tectum may play the same
      role.

PMID- 9273854
TI  - Corpus callosum: neuropathology.
AB  - The anatomical and histological structure of Corpus callosum is analysed, mainly
      in relation with cell composition and fibre distribution. The vascularization of
      Corpus callosum is analyzed in relation with the distribution of the supplying
      arteries and the fine organization of small vessels. The first part of the
      presentation deals with damages of corpus callosum as a consequence of
      hemorrhagic and ischemic vasculopathies. The lesions may be direct or indirect;
      the latter follow the distruction of hemispheric areas interconnecting through
      the corpus callosum or occur as the product of reduced flow in the territories of
      carotid and vertebral arteries. A special mention is dedicated to the
      anatomoclinical syndromes developing after damages to the anterior or posterior
      section of Corpus callosum. The second part deals with specific diseases such as
      Marchiafava-Bignami's disease, which is treated as an example of glial cell
      pathology and chronic edema. The third part deals with tumors. Besides lymphomas
      which need a separate consideration for their modality of growth, neuroepithelial
      tumors are discussed. The most important problem is that of invasion through the
      Corpus callosum. The cell traffic in this structure with all the connected
      questions about cell migration, adhesiveness and motility are presented.
      Pathology of Corpus callosum is extended also to anatomically related median
      structures such as fornix and septum pellucidum. The latter is one of the
      principal pathways of diffusion in gliomas.

PMID- 9273857
TI  - Callosotomy for drug resistant generalized seizures.
AB  - We report our series of drug resistant epileptic patients submitted to
      callosotomy. The 25 patients were affected by severe epilepsy with invalidating
      generalized seizures with fall, lacking of indication for ablative surgery.
      Nineteen patients, with at least 1 year of follow-up, were considered for this
      study. The surgical outcome was classified as: class A), seizure disappearance;
      class B) 80%, class C) 80-50%, class D) less than 50% seizure reduction; E)
      increase of seizure frequency. The follow-up analysis shows that the better
      results are obtained with the generalized seizures, in particular the GTA. Our
      surgical results are discussed considering the data of the literature: about the
      functional anatomy of the Corpus Callosum, the experimental studies and the
      clinical series published on callosotomized epileptic patients.

PMID- 9273858
TI  - Transcallosal approach to tumors of the third ventricle. Surgical results and
      neuropsychological evaluation.
AB  - A series of 34 patients with tumours of the third ventricle were operated on by a
      transcallosal route. Basal extrinsic lesions compressing or invading the
      ventricle as well as tumours located in the pineal area were excluded from this
      review. Tumours were approached by a transforaminal entry in 16 cases (47%), by
      an interforniceal route in 11 (32%), by a subchoroidal entry in 4 (14%) and by a
      combined transforaminal and subchoroidal entry in 3 (9%). Four out of 34 patients
      were submitted to a second operation, through the same approach corridor: 2 for
      an incomplete removal of an intrinsic tumour and 2 for a late regrowth.
      Postoperative mortality rate accounted for 5.8% (2 patients). Major post
      operative complications were hemiparesis (4 patients) and diabetes insipidus (4
      patients), that were transient in 3. Akinetic mutism like status was observed in
      only 1 patient. Postoperative psychic disturbances were noticed in 5 cases. Nine
      out of 21 patients (62%) with preoperative hydrocephalus required a permanent CSF
      shunt. Histology revealed that 21 tumours (62%) were intraaxial (4 pilocitic
      astrocytoma, 10 low grade glioma, 1 giant cell astrocytoma, 1 subependymoma, 4
      ependymoma/ependymoblastoma, 1 neurocitoma) and 13 (38%) were extraaxial (8
      colloid cyst, 2 craniopharingioma, 1 ectopic pituitary adenoma, 1 lymphocytic
      hypophysitis and 1 metastasis). Total excision of third ventricle tumours was
      achieved in all patients with extraaxial tumours and in 62% and 71% of intraaxial
      tumours with the first and second surgical procedure respectively. Ten out of 34
      patients of this series were submitted to a complete neuropsychological
      evaluation at an interval of 2-9 years after surgery. Memory tests were
      pathological in 2. Disconnection signs were constantly absent. Control function
      were preserved. Transcallosal approach remains the best microsurgical method of
      third ventricle tumours treatment. This route provides the capability for a
      superior visualization of the entire cavity of the third ventricle through
      different corridors. Permanent neurological and neuropsychological deficits are
      not frequent. Epilepsy, that accounted for 28% in patients submitted to
      transcortical transventricular approach to third ventricle tumours, was never
      noticed in this series operated on through a transcallosal route.

PMID- 9273859
TI  - Callosotomy for intractable epilepsy: overall outcome.
AB  - The effectiveness of callosotomy to the control of medically intractable epilepsy
      is still discussed fifty years after the first reported cases. Nevertheless
      patient selection, type of seizures and epileptic syndromes are now better
      determined. Atonic and tonic astatic seizures characterized both by clinical and
      electroencephalographical specific patterns, are the most responsive. A favorable
      outcome, from > 50% reduction in seizure frequency to a complete cessation, is
      obtained from 60 to 80% of the patients. For tonic-clonic seizures, favorable
      outcome fluctuates from 40% to 80% principally according to the extension of the
      section. Other types of seizures are not indicated for callosotomy even though
      some improvement may be observed. Symptomatic secondary generalized epilepsy with
      predominent unilateral lesion and epileptic focus on bifrontal lobe epilepsy are
      the most suitable indication. True generalized epilepsies are associated with a
      less favorable outcome. Indeed, axial spasms, the most frequent type of drop
      attacks in the Lennox-Gastaut syndrome, probably do not have a cortical origin.
      Quality of life and social adjustment are assessed from a cohort of 20 cases of
      anterior two-third callosotomy. Actual benefits are in close connection with both
      seizure relief and age at operation. To obtain a gain in social independence not
      only seizure control has to be better but also surgery must be performed sooner.

PMID- 9273860
TI  - Neuropsychological alterations after split-brain surgery.
AB  - Neuropsychological changes following corpus callosotomy depend on the degree of
      the callosal section, the portion sectioned and the patient's age at the time of
      the surgery. Anterior section frequently results in transient hemiparesis of the
      non-dominant leg and temporary difficulties in initiating speech. Posterior
      section is followed by disconnection symptoms in the sensory modalities which can
      be demonstrated when input is lateralized and one hemisphere is denied access to
      the information received by the other. Visual and tactile stimuli presented to
      the non-dominant hemisphere are no longer verbally identified due to
      disconnection from the language-dominant hemisphere. Total callosotomy
      additionally interrupts interhemispheric communication between the motor regions.
      This results in deficits in bimanual coordination and apraxia of the non-dominant
      hand to verbal commands. Some of the symptoms subside, probably due to increased
      use of ipsilateral sensory and motor pathways. Others are permanent. However,
      they are not disabling since unrestricted scanning of the environment ensures
      bilateral representation of sensory experience. Cognitive functions are
      frequently improved, although preexisting lateralized deficits may be
      exacerbated. Learning of new material is difficult for some patients with
      lateralized temporal lobe dysfunction in whom interhemispheric compensation is
      abolished by the surgery. Language deficits are observed mainly in patients with
      crossed dominance. Studies in children reveal that callosotomy performed before
      puberty is not followed by permanent disconnection deficits. This may be
      attributable to the greater neural plasticity of the immature brain.

PMID- 9273861
TI  - Neuropsychological outcome of corpus callosotomy in children and adolescents.
AB  - The effect of corpus callosotomy on cognitive functioning, social adjustment and
      motor behavior was studied in 25 pediatric patients. In order to assess age
      related differences in cerebral adjustment, the sample was divided into two
      groups, one group operated on before and the other after the age of 13 years. Pre
      and postoperative data were collected from all patients by means of standardized
      neuropsychological tests. When possible, the children were also submitted to
      simple interhemispheric transfer tasks in the tactile modality. Results revealed
      that all patients benefited from the callosotomy, regardless of their age and
      their mental capacities at the time of the surgery. The greatest improvements
      were observed in social adjustment. Generally, neuropsychological outcome
      paralleled neurological outcome. In keeping with the plasticity hypothesis, the
      young group showed greater gains than the older group. The latter showed similar
      sequelae as the adult split-brain patients described in the literature. Number of
      years of uncontrolled seizures was not related to neuropsychological outcome.
      Higher IQ was associated with better outcome in the young group, mainly because
      this group was more severely retarded and had more to gain from the surgery than
      the older group. However, mental retardation should not be an exclusion criterion
      for corpus callosotomy in view of the potential benefit of the surgery for the
      patient and his/her family.

PMID- 9273862
TI  - Neuropsychological and neurophysiological consequences of partial callosotomy.
AB  - Sixty-five patients with lesions affecting the third ventricle (54 patients) or
      the corpus callosum itself (11 patients) underwent partial callosotomy or a
      circumscribed callosal resection. Before the surgery 20 patients were studied
      using the battery of cognitive, affective and behavioural tests which was
      repeated 10 and 100 days after surgery. No disconnection syndrome was over
      observed after the partial commissurotomy. Transcranial magnetic stimulation over
      the sensorimotor cortex was performed in 10 patients to determine conduction time
      of callosal fibres by measuring inhibition of tonic voluntary electromyographic
      activity in muscle's ipsilateral to the activated hemisphere. It was found that
      this inhibition was absent in patients with lesions of the trunk of the corpus
      callosum and present in patients with lesions of the genu or splenium. In
      addition magnetic resonance imaging measurements of the corpus callosum were
      performed in 40 normal subjects to establish a classification system for corpus
      callosal area. The results showed a wide variability of the cross-sectional area
      of the corpus callosum. The comparison of the shape of the corpus callosum lead
      to a categorisation according to the presence and location of depressions on its
      surface.

PMID- 9273863
TI  - Modifications in morphology of epileptic seizures after callosotomy.
AB  - The callosotomy on drug-resistant epileptic seizures may abolish or reduce their
      frequency and may modified the morphology of different kind of seizures. Our
      series is composed of 36 patients. Drop-attacks and complex partial seizures (CP)
      were present in all patients, generalized tonic-clonic seizures (GTC) in 16
      (44.4%) and simple partial seizures (SP) and myoclonic attacks (MY) in 6 patients
      each. We found two kinds of modifications: a) lateralization of hypotonia which
      becomes hemisomatic, with lateral bending to the hypotonic side; b) different way
      of falling, due not only to the lateralization of hypotonia but also to the
      gradual impairment of muscle tone. Modifications in CP mainly concerned
      automatisms, which disappeared in 39.1% of patients, while 34.8% of them had a
      significant reduction in automatisms; this reduction consisted in simplification
      of automatic movements and in shorter duration of seizures.

PMID- 9273864
TI  - EEG Patterns after callosotomy.
AB  - In 36 patients with drug-resistant epilepsy submitted to anterior callosotomy (27
      cases), to two-stage total callosotomy (8 cases) and to posterior callosotomy (1
      case) the EEG variations concerning background activity, focal activity and sharp
      waves (SW) bisynchronous activity were evaluated. EEG modifications observed
      after callosotomy are the following: background rhythm tends to be better
      organised as spectral analysis demonstrated, this finding usually coincide with
      reduction of bisynchronous discharges. It appears that improvement in background
      activity cannot be correlated with outcome, but it seems to be to some extent
      since at the same time cognitive functions also seem to improve; however, this
      last aspect need to be checked in much larger series. The number and location of
      EEG foci do not change, but they appear to be more active; this is likely to
      depend only on the concomitant reduction of bisynchronous activity. No
      correlation seems to exist between the number and the location of foci, which are
      generally multiple. Lateralization of bisynchronous discharges as well as the
      reduction of their frequency and duration were observed. However, the clinical
      course is quite different: in some patients we have achieved good clinical
      responses in others postoperative results were poor. Lateralization of
      bisynchronous discharges is never absolute, on the grounds that in prolonged
      recordings bisynchronous discharges are nearly always present. Bisynchronous
      discharges in some cases are alternatively predominant in both hemispheres even
      within minutes or seconds. It was observed that after certain time, generally
      some months, lateralized discharges tend to generalize again, confirming that
      corpus callosum is replaced in discharge diffusion by other structures (brain
      stem, diencephalon).

PMID- 9273865
TI  - Mutism in 36 patients who underwent callosotomy for drug-resistant epilepsy.
AB  - Thirty-six drug-resistant epileptic patients submitted to callosotomy were
      studied. Anterior callosotomy was performed in 27 patients, total two-stage
      callosotomy was performed in 8 patients and 1 patient had only posterior
      callosotomy. We found mutism in 10 patients (2 after complete callosotomy and 8
      after anterior section). The patients did not speak, but the comprehension was
      present: they were able to carry out orders and to write. Their attitude to the
      environment was characterized by complete indifference. The mutism was always
      transient, lasting from 4 to 25 days (mean 7 days). Regression of mutism was
      always complete. We think that this complication should be chiefly attributed
      mainly to surgical manipulation, even if it is impossible to completely exclude a
      multi-factorial etiology.

PMID- 9273866
TI  - Interhemispheric transfer of learning in brain-damaged patients.
AB  - The purpose of the present study was to assess some of the mechanisms involved in
      the compensation of impaired cerebral functions in patients with unilateral brain
      lesions. Thirty patients with lesions of the left (dominant) hemisphere and 30
      patients with lesions of the right (minor) hemispheres were studied. The subjects
      were blindfolded and submitted to some tests of manual performance, i.e. the
      relief maze test and identification of geometrical figures. The performances of
      each hand were determined, before and after ipsilateral and contra-lateral
      training. A post-training improvement index was also established. The hand
      related to the damaged hemisphere showed the worse performance. The post-training
      improvement was lower for the damaged hemisphere. The learning transfer test
      after contralateral training showed an improvement of the damaged hemisphere
      significantly greater than that of the healthy one. The authors conclude that in
      patients with unilateral brain lesions, the healthy hemisphere can compensate for
      some of the impaired higher cerebral functions by a transfer of information and
      learning to the damaged one.

PMID- 9273867
TI  - A callosal disconnection syndrome of vascular origin.
AB  - OBJECTIVE: To study the after-effects of a selective lesion of the corpus
      callosum on the capacity in transferring spatial information on arm posture
      derived from kinesthesia and vision. DESIGN: Neuropsychological and
      psychophysical evaluations of a patient with callosal damage. SETTING: Institute
      of Neurology, University of "Tor Vergata", Rome, Italy and Research Centre, IRCCS
      "S. Lucia", Rome, Italy. PATIENT: P.V., a 59 years old man suffering from a
      vascular lesion of the left half of corpus callosum and left callosal radiations.
      MEASURES: Sensori-motor and cognitive tasks. Exo- and egocentric pointing
      abilities tasks. RESULTS: Impairments due to a disconnection between the two
      cerebral hemispheres were pointed out. About pointing abilities, errors were
      greater when each hand pointed to the remembered location of the other hand.
      Errors decreased dramatically with eyes open for right hand pointing to
      remembered location of left and right hand, and left hand pointing to remembered
      location of left hand. Open eyes left hand pointing to remembered location of
      right hand remained as poor as with eyes closed. CONCLUSIONS: The results appear
      compatible with the following network: visual information from striate and
      extrastriate cortex is passed forward to parietal cortex bilaterally (even in PV
      due to the splenium sparing). Kinesthetic information from parietal cortex of
      left and right hemisphere converge on a single visuokinesthetic center,
      lateralized to the left hemisphere. Information about limb position in three
      dimensional space is then encoded in body-centered coordinates and passed forward
      to motor and premotor cortex in the frontal lobe. These frontal regions are those
      disconnected in PV.

PMID- 9273868
TI  - Surgical treatment of glial tumours of genus corpus callosum and medial parts of
      frontal lobes.
AB  - The analysis was done of surgical treatment possibilities of glial tumours
      located in genus corpus callosum and medial parts of frontal lobes. It was shown
      that in most cases it's possible to remove these tumours totally or sub-totally
      with good clinical effect.

PMID- 9273869
TI  - Surgical treatment of anterior callosal tumors.
AB  - OBJECTIVE: Thirteen patients with neoplasm of anterior corpus callosum have
      undergone our observation during the last two years. METHODS: For the diagnosis,
      all the patients underwent TC, NMR and stereotactic biopsy. In 6 cases with
      glioblastomas, a radiation treatment was adopted. The other 7 patients underwent
      total surgical treatment in 5 cases, and partial in 2 cases, as documented by
      postoperative contrast-enhanced CT scanning. Histologically, there were: 3
      glioblastomas, 1 grade III astrocytoma, 1 neuroblastoma (PNET), 2 pilocytic
      astrocytomas. RESULTS: Neuropsychological tests carried out on the 5 patients
      still living showed persistent disturbances of verbal memory in all five and
      disturbances of verbal phonological fluency in 3 cases. No patient presented
      apraxia, dysgraphia and dyslexia. CONCLUSIONS: Thus, no severe neuropsychological
      deficits developed after surgical treatment of anterior callosal tumors.

PMID- 9273870
TI  - Cognition and quality of life in patients after transcallosal microsurgery for
      midline tumors.
AB  - OBJECTIVE: The transcallosal route has been propagated as a safe approach to
      midline tumors. The present study was performed in order to elucidate the
      neurobehavioral late sequelae in patients after transcallosal microsurgery on
      near-midline tumors. EXPERIMENTAL DESIGN: The present study was performed
      retrospectively with a delay between surgery and follow-up examination ranging
      from 2 to 36 months (mean 10.2 months). SETTING: The study was performed in the
      Department of Neurosurgery, University Hospital of the University of Technology
      (RWTH) Aachen, Germany. PATIENTS: A consecutive series of 18 patients treated for
      an intracranial lesion by transcallosal surgery was included into the study. The
      patients had to be not younger than 16 and not older than 67 years. The age mean
      was 38.9 years (range 16 to 65 years). INTERVENTIONS: The surgical approach was
      performed along the falx cerebi under microneurosurgical conditions with direct
      use of the microscope after opening the dura. MEASURES: Beyond neurological
      examinations, the patients were submitted to an extensive neuropsychological
      testing battery. Furthermore, quality of life was examined by means of a
      questionnaire. RESULTS: Surgery was performed without persistent new neurological
      deficits. Cognitive deficits were found in short- and long-term memory, motor
      fine-coordination, reaction time, divided attention and fronto-cortical capacity.
      The quality of life was particularly impaired in the area of cognitive capacity
      in daily life. These findings could be related to the duration of preoperative
      symptoms and to the tumor location. CONCLUSIONS: The deficits found cannot be
      explained by surgical damage to the corpus callosum itself. Rather, they seem to
      correspond to an extra-callosal pathology. Further studies with a prospective
      evaluation of larger patient samples are called for in the future.

PMID- 9273871
TI  - Asbestos disease in foundrymen.

PMID- 9273872
TI  - Asbestos disease in foundrymen.

PMID- 9273873
TI  - Placebo response in environmental disease. Chelation therapy of patients with
      symptoms attributed to amalgam fillings.
AB  - Treatment of patients who attribute their environmental illness to mercury from
      amalgam fillings is largely experimental. On the Symptom Check List, overall
      distress, and somatization, obsessive-compulsive, depression, and anxiety symptom
      dimensions, were increased in 50 consecutive patients examined, and Eysenck
      Personality Questionnaire scores suggested less extroversion and increased degree
      of emotional liability. Succimer (meso-2, 3-dimercaptosuccinic acid) was given at
      a daily dose of 30 mg/kg for five days in a double-blind, randomized placebo
      controlled trial. Urinary excretion of mercury and lead was considerably
      increased in the patients who received the chelator. Immediately after the
      treatment and 5 to 6 weeks later, most distress dimensions had improved
      considerably, but there was no difference between the succimer and placebo
      groups. These findings suggest that some patients with environmental illness may
      substantially benefit from placebo.

PMID- 9273874
TI  - Occupational fatalities among older workers in the United States: 1980-1991.
AB  - Workers aged 65 and older had a workplace fatality rate of 2.6 times that of
      workers aged 16 to 64 for 1980 through 1991 (14.1 per 100,000 vs 5.4), according
      to National Traumatic Occupational Fatalities (NTOF) data. The highest rates were
      in mining, agriculture, and construction. Compared with younger workers, older
      men were at an elevated risk for fatalities caused by machines, and older women
      for fatal falls and homicide. Prevention efforts should focus on older workers in
      agricultural settings, as well as those at increased risk of workplace falls or
      violence.

PMID- 9273876
TI  - Screening for carpal tunnel syndrome in the workplace. An analysis of portable
      nerve conduction devices.
AB  - Several devices have been developed for rapid motor or sensory median nerve
      conduction testing. We evaluated the validity and reliability of the
      Neurosentinel (NS) and NervePace (NP) electroneurometer for sensory and motor
      testing, respectively, compared with formal electrodiagnostic studies (EDS), and
      examined their potential role in workplace screening for carpal tunnel syndrome
      (CTS). Thirty-two working subjects without CTS were examined and tested with the
      NS, NP, and EDS, and retested one week later. Subjects were selected who did not
      have CTS, other hand or nerve problems, or jobs with significant ergonomic risks,
      in order to decrease the likelihood of changes over time in median nerve
      function. Mean correlations of NP and NS with EDS latencies ranged from r = 0.069
      to r = 0.85, with somewhat better correlation for NS (sensory) than NP (motor).
      Test-retest reliability was greatest for motor EDS (r = 0.86 to 0.91) and similar
      for sensory EDS, NS, and NP (r = 0.72 to 0.79); mean results were very similar.
      Based on the observed relationship between NS or NP and EDS results, confidence
      intervals were calculated to represent the range of EDS results consistent with a
      single NS or NP measurement. These intervals ranged from +/- 0.3 milliseconds
      (ms) for NS to +/- 0.6 msec for NP, with similar ranges for change over time in
      an individual. The magnitude of these intervals for a single test or individual
      implies that the NS and NP are unlikely to identify individuals with CTS or to
      detect changes over time that are not accompanied by symptoms or signs. The
      screening devices are not likely to be useful in confirming early CTS, when
      single latency values may be normal, and detailed EDS may be necessary to detect
      nerve entrapment. Compared with EDS, these devices have moderate validity and
      similar reliability; they are probably most useful for cross-sectional or
      longitudinal studies of groups, but care must be taken in using them for pre
      placement or surveillance tests of individual workers. False-positive results may
      lead to discrimination, inappropriate referrals and interventions; false-negative
      tests can result in inappropriate reassurance and missed opportunities for
      intervention.

PMID- 9273875
TI  - Metal fume fever: characterization of clinical and plasma IL-6 responses in
      controlled human exposures to zinc oxide fume at and below the threshold limit
      value.
AB  - Results from animal and preliminary human exposure studies have called into
      question whether the 5 mg/m3 8-hour time-weighted average threshold limit value
      (TLV) for zinc oxide fume is sufficient to protect workers against metal fume
      fever. The objectives of this study were to determine the clinical effects of
      exposures to low concentrations of zinc oxide and to ascertain whether these
      exposures elevated circulating levels of specific cytokines, which could account
      for the symptoms of the metal fume fever syndrome. Thirteen resting naive
      subjects inhaled, on separate days, air and 2.5 and 5 mg/m3 of furnace-generated
      zinc oxide fume for 2 hours. Subjects recorded symptoms and temperature and had
      blood drawn before and after each exposure. The mean (+/- SE) maximum rise in
      oral temperature at 6 to 12 hours after exposure was 1.4 +/- 0.3 degrees F after
      5 mg/m3, compared with 0.6 +/- 0.5 degrees F after air exposure (P < 0.05). Mean
      temperature was also elevated after exposure to 2.5 mg/m3 zinc oxide (1.2 +/- 0.3
      degrees F). In a parallel fashion, plasma levels of interleukin 6 (IL-6), a
      pyrogen, were significantly elevated after exposure to 5 mg/m3 zinc oxide. Mean
      IL-6 values (pg/mL) at pre-exposure and at 3 and 6 hours post-exposure were 1.9
      (+/- 0.6), 2.8 (+/- 0.7), and 2.9 (+/- 0.6), respectively, on the air day and 1.6
      (+/- 0.6), 4.4 (+/- 1.2), and 6.4 (+/- 1.1) on the 5 mg/m3 zinc oxide day. Zinc
      oxide exposure did not significantly affect plasma levels of tumor necrosis
      factor. Total symptom scores peaked 9 hours after the 5 mg/m3 zinc oxide
      exposure. Myalgias, cough, and fatigue were the predominant symptoms reported.
      Inhalation of zinc oxide for 2 hours at the current TLV of 5 mg/m3 produces fever
      and symptoms along with elevation in plasma IL-6 levels.

PMID- 9273877
TI  - The effects of smoking outside workplaces on non-regular smokers.
AB  - The introduction of workplace smoking bans has resulted in smokers smoking
      outside their workplaces (exiled smoking). Social identity theory postulates that
      this may cause antagonism between smokers and non-smokers, or where non-smokers
      were friends with smokers, pressure on non-smokers to smoke. This study examines
      perceptions and beliefs about exiled smoking in 166 non-smoking workers. They saw
      smokers as having a work benefit not available to them, but otherwise they were
      generally not drawn to the activity. Half had joined smokers outside for breaks,
      but of these only one-third had ever smoked. Those would smoked reported that
      they did not have a regular pattern of joining the same group of smokers.
      Although it may provide a conduit for susceptible non-smokers to take up smoking,
      exiled smoking does not appear to influence those who are not otherwise
      vulnerable.

PMID- 9273878
TI  - A case-control study of lung cancer among Vietnam veterans.
AB  - Because of concerns among veterans over Agent Orange exposure, the Department of
      Veterans Affairs (VA) has conducted a series of studies of specific cancers among
      Vietnam veterans. Lung cancer is the topic of investigation in this report. The
      VA's Patient Treatment File (PTF) was used to identify 329 Vietnam era veterans
      with a diagnosis of lung cancer made between 1983 and 1990. The PTF is a
      computerized hospitalized database of inpatient records, including patients'
      demographic data, and diagnoses. A record is created for each patient discharged
      from any one of the VA's Medical Centers. Variables abstracted from the military
      record include education, race, branch of service, Military Occupational
      Specialty Code, rank, and units served within Vietnam. Two hundred sixty-nine
      controls were randomly selected from the PTF file of men hospitalized for a
      reason other than cancer. A second control group numbering 111 patients with
      colon cancer was also selected from the PTF file. Data were also gathered on
      exposure to Agent Orange through the location of each individual ground troop
      veteran's unit in relation to an area sprayed and the time elapsed since that
      area was sprayed. The crude odds ratio between service in Vietnam and lung cancer
      was of borderline significance (odds ratio = 1.39 with 95% confidence interval =
      1.01-1.92). The relationship disappeared when the confounder year of birth was
      considered. We conclude from these data that there is no evidence of increased
      risk in lung cancer associated with service in Vietnam at this time.

PMID- 9273879
TI  - The influence of personal variables on work-related low-back disorders and
      implications for future research.
AB  - Work-related low-back disorders (LBDs) continue to be one of the single largest
      sources of compensation costs. The relative contributions of personal, workplace,
      organizational, and environmental variables to the development and severity of
      LBDs are not completely understood. The inclusion of personal variables in
      epidemiologic studies of LBDs has been inconsistent, and different authors have
      different opinions concerning the importance of such variables. Personal
      variables either known or suspected to influence outcomes are discussed to
      elucidate the importance of these variables with respect to understanding LBDs
      and conducting epidemiological studies in industry. The authors suggest that age,
      gender, injury history, relative strength, smoking, and psychosocial variables be
      studied further, and that height, weight, pathologies, genetic factors, maximum
      oxygen uptake, and absolute strength are unlikely to produce significant effects
      in industrial populations.

PMID- 9273880
TI  - Hazardous materials incidents: the Washington Poison Center experience and
      approach to exposure assessment.
AB  - Hazardous materials incidents include gas and vapor releases, spills, explosions,
      and fires. Incidents involving human exposure are challenging for most health
      care providers because of the vast number of potential chemicals involved,
      frequently incomplete incident information, and limited experience in exposure
      assessment. To facilitate improved evaluation and treatment of patients with
      chemical exposures, the Washington Poison Center established the Hazardous
      Materials Exposure Information Service in 1994. During the first 33 months of
      operation, this service has provided information on 70 incidents, involving a
      total of 1120 exposed individuals, including 501 patients treated in medical
      facilities. This paper reviews these incidents, the process used to collect
      information from the incidental scene, and selected techniques for evaluating the
      extent of individual chemical exposure.

PMID- 9273881
TI  - Ergonomic risk exposure and upper-extremity cumulative trauma disorders in a
      maquiladora medical devices manufacturing plant.
AB  - Workers at a Nogales, Mexico, maquiladora plant that assembles medical devices
      were studied to determine the prevalence of upper-extremity cumulative trauma
      disorders (CTD). Subjects included production workers employed 6 months or
      longer; of the 148 eligible workers, 145 (98%) participated. Subjects had a mean
      age of 24.6 years (SD = 5.2; range, 17 to 45) and the mean length of employment
      was 3.5 years (SD = 2.5; range, 0.5 to 14). Job tasks were videotaped and
      analyzed for ergonomic risk factors, using pre-defined criteria. All jobs
      performed by study subjects were found to involve one or more ergonomic risk
      factors associated with the development of CTD. A CTD questionnaire and screening
      physical examination format, similar to that used by the National Institute of
      Occupational Safety and Health (NIOSH) in a chicken processing plant study, were
      administered. Period prevalence of CTD within the previous year, as reported on
      the questionnaire, was 28%. Prevalence of CTD was 17%, using data from the
      screening physical examination. Point prevalence (current pain data from the
      questionnaire plus positive symptoms on the screening physical examination) was
      15%. CTD was reported more frequently in women than men (46% and 25%,
      respectively; P < 0.05) and in subjects who had worked at the plant less than one
      year (50%; P < 0.05). Workforce turnover (3% monthly) may have resulted in those
      affected by CTD leaving employment, reducing the apparent CTD rate in experienced
      workers.

PMID- 9273882
TI  - Conformational analysis of homochiral and heterochiral diprolines as beta-turn
      forming peptidomimetics: unsubstituted and substituted models.
AB  - The effect of replacing one of the proline residues in either unsubstituted
      homochiral or heterochiral diproline segments with either a 2- or a 3-substituted
      prolyl residue on the allowed conformational of the diproline template has been
      examined. In heterochiral (L-D) diprolines, placement of a 2-methyl-D-proline
      residue in the i + 2 position and placement of either a cis- or trans-3-methyl-L
      proline residue in the i + 1 position results in substituted diproline peptides
      that adopt the same type II beta-turn conformation as that defined experimentally
      for the unsubstituted diproline peptides. In contrast, placement of a cis-3
      methyl-D-proline residue in the i + 1 position of a homochiral (D-D) diproline
      peptide seems to promote a different conformation than that seen in the
      unsubstituted case, whereas the trans-3-methyl-D-proline residue seems to provide
      a stabilizing influence for the predicted type VI' beta-turn. The demonstrated
      ability of certain substituted diproline templates to adopt predictable
      conformations coupled with the development of asymmetric synthetic routes to both
      2- and 3-substituted prolyl residues, capable of mimicking a variety of side
      chains should make these templates useful tools in designing specific turn mimics
      of biologically active molecules.

PMID- 9273883
TI  - Variation of acidity constants of peptides in acetonitrile-water mixtures with
      solvent composition: effect of preferential solvation.
AB  - The dissociation constant values of a series of peptides in 5.54, 10, 16.30,
      25.03 and 50% (w/w) acetonitrile-water mixed solvents at 298.15 K were determined
      according to the criteria endorsed by IUPAC. A pronounced change in the acid-base
      pK values of carboxylic, phenol and thiol groups was observed as the solvent was
      enriched in acetonitrile. By contrast, pK values of protonated amino-terminal
      groups were influenced slightly as the solvent was enriched in acetonitrile,
      although continually increasing pK values were observed. The variation of the pK
      values obtained, over the whole composition ranged studies, was explained by
      taking into account the preferential solvation of electrolytes in acetonitrile
      water mixtures. To obtain pK values in all possible binary solvent acetonitrile
      water mixtures, relationships between pK values and different bulk properties
      were examined and the Linear Solvation Energy Relationships methodology was
      applied. The pKa values were then correlated with the Kamlet-Taft, phi, alpha and
      beta solvatochromic parameters of acetonitrile-water mixtures. The equations
      obtained allowed calculation of the pK values of peptides in acetonitrile-water
      mixtures up to 50% (w/w) and thus permitted the acid-base behavior of these
      substances in the widely used acetonitrile-water media to be known.

PMID- 9273884
TI  - A binding study of phospholipase A2 with lecithin, lysolecithin and their
      tetrahedral intermediates using molecular modeling.
AB  - We used molecular modeling to examine the binding of 1,2-dioctanoyl-sn-glycero-3
      phosphocholine (a lecithin), 1-octanoyl-sn-glycero-3-phosphocholine (a
      lysolecithin) and their tetrahedral intermediates in the catalytic site of
      phospholipase A2 (PLA2). We performed energy minimization on each complex,
      computed the binding energy, determined the relative binding energy among the
      complexes and calculated the difference in inter- and intramolecular energies of
      the components in the complexes. We found that the calculated orientation of the
      sn-1 ester bond of lysolecithin in the active site is similar to that of the sn-2
      ester bond in lecithin, thus permitting PLA2 to hydrolyze lysolecithin using the
      same mechanism as it uses to hydrolyze lecithin. On the other hand, the binding
      of lecithin is energetically more favorable by 4.5 kcal/mol than the binding of
      lysolecithin to the enzyme, and the binding of the lecithin tetrahedral
      intermediate is also energetically more favorable by 19.7 kcal/mol than the
      binding of the lysolecithin tetrahedral intermediate to the enzyme, which
      explains why lecithin is a better substrate than lysolecithin in the catalytic
      site. These results indicate that the activation energy for the hydrolysis of
      lysolecithin is higher than that for lecithin, consistent with the observed
      slower rate for the hydrolysis of lysolecithin.

PMID- 9273885
TI  - Studies on the peptide corresponding to residues 34-47 of bovine factor X.
AB  - Calcium binding studies of a 14-residue peptide corresponding to the 37-46
      sequence of bovine factor X were performed using calcium ion selective electrode
      titrations and equilibrium dialysis. The presence of gamma-carboxyglutamic acid
      residues at positions 36 and 40 coupled with the assumption that the peptide
      would bind calcium ions also prompted an investigation of possibly secondary
      conformational changes in the peptide by use of circular dichroism spectroscopy.
      Equilibrium dialysis revealed a single relatively weak calcium binding site (log
      Ka = 2.39); an ion selective electrode experiment confirmed this result (log Ka =
      2.17). The peptide maintained a random coil conformation throughout the calcium
      ion titrations as measured by circular dichroism.

PMID- 9273886
TI  - Differential involvement of disulfide bridges on the folding of a scorpion toxin.
AB  - Leiurotoxin I is a neurotoxin, blocker of Ca(2+)-activated apamin-sensitive K+
      channel, purified from the venom of the scorpion Leiurus quinquestriatus
      hebraeus. It is a 31-residue polypeptide reticulated by three disulfide bridges,
      i.e. Cys3-Cys21, Cys8-Cys26 and Cys12-Cys28. To investigate the role of these
      disulfide bridges in the folding of this toxin, analogs lacking one disulfide
      bridge were synthesized. The structures of two analogs in which two half-cystines
      were placed by alpha-aminobutyrate residues to suppress one disulfide bridge,
      were analyzed by 1H NMR. The NMR studies reveal a three-dimensional structure
      identical with the native toxin for the analog lacking disulfide bridge Cys3
      Cys21 and a loss of organized structure for another analog lacking disulfide
      bridge Cys12-Cys28. These analogs are, respectively, fully active and weakly
      active (2% of the residual activity) when tested in vitro for their ability to
      interact with their receptor channel and in vivo for their neurotoxic activity in
      mice. This suggest that disulfide bridge Cys12-Cys28 is essential for the folding
      process. In contrast, the lack of disulfide bridge Cys3-Cys21 does not affect the
      folding and the maintenance of bioactive conformation of Leiurotoxin I.

PMID- 9273887
TI  - Synthesis and biological properties of beta-MePhe3 analogues of deltorphin I and
      dermenkephalin: influence of biased chi 1 Phe3 residues on peptide recognition
      for delta-opioid receptors.
AB  - Using the method of conformational constraint, we have designed and synthesized
      analogues of deltorphin I and dermenkephalin containing each of the four
      stereoisomers (2S,3S; 2S,3R; 2R,3S; 2R,3R) of the unusual amino acid beta
      methylphenylalanine in position three. The potency and selectivity of these
      analogues were evaluated by radioreceptor binding assays in the rat brain using
      [3H]CTOP (mu-ligand) and[3H]p-C1Phe4]DPDPE (delta-ligand), and by bioassay using
      the mouse vas deferens (delta-receptor assay) and guinea pig ileum (mu-receptor
      assay) assays. The substitution of a beta-MePhe for Phe3 in deltorphin I and
      dermenkephalin has a large and variable effect on the bioactivities of the
      synthesized analogues. The synthesized analogues are somewhat less potent than
      the native peptides. Both [(2S,3R)-beta-MePhe3]deltorphin and [(2S,3R)-beta
      MePhe3] dermenkephalin are more selective, however, and interact essentially
      specifically with the receptor in the binding assays and bioassays. The bioassay
      data in vitro of the synthesized analogues of deltorphin I and dermenkephalin
      follow the same general trends as the receptor binding data. These results
      demonstrate that topographical modifications of the side-chain conformation of
      critical structural moieties in a ligand can significantly modulate both the
      potency and receptor selectivity for ligands that have multiple sites of
      biological activity, and they illustrate that this approach has general
      application to peptide and peptidomimetic ligand design.

PMID- 9273888
TI  - Conformational study of vasoactive intestinal peptide by computational methods.
AB  - The conformational profile of vasoactive intestinal peptide (VIP) was
      characterized using computational methods. The strategy devised included a close
      examination of the conformational profile of the first 11 residues fragment
      followed by a study that considered the compatibility of the different
      conformations found with a continuation of the polypeptide chain in a alpha
      helical conformation. Accordingly, a detailed analysis of the conformational
      preferences of the N-terminal fragment of VIP(1-11) was carried out within the
      framework of the molecular mechanics approach, using simulated annealing in an
      iterative fashion as the sampling technique. In a second step, low-energy
      structures of the fragment were fused to the remainder of the VIP chain in the
      form of two noninteracting alpha-helices, according to a model of the structure
      of the peptide proposed from NMR studies. After investigation for compatibility
      of each of the low-energy structures of VIP(1-11) with the two helical regions by
      energy minimization, only 5 of 35 structures were discarded. Analysis of the
      structures characterized indicates that most of the conformations of VIP(1-11),
      including the global minimum, can be described as bent conformations.
      Conformations exhibiting alpha-turns and beta-turns, previously proposed by NMR
      studies were also characterized. The conformational analysis also suggests that
      the common structural features found in VIP(1-11) should also be present in VIP.
      Finally, because of the sequence homology between VIP and Peptide T, and the fact
      that both are ligands of the CD4 receptor, both sets of low-energy conformations
      were compared for similarity. The relevance of these results as guidance of the
      design of new peptide analogs targeted to the CD4 receptor is also discussed.

PMID- 9273889
TI  - Synthesis and cystine/cysteine-catalyzed oxidative folding of the amaranth alpha
      amylase inhibitor.
AB  - We report here the total synthesis of the alpha-amylase inhibitor (AAI), a 32
      residue-long peptide with three disulfide bridges, isolated from amaranth seeds
      (Chagolla-Lopez, A., Blanco-Labra, A., Patthy, A., Sanchez, R. & Pongor S. (1994)
      J. Biol. Chem. 269, 23675-23680). The synthesis was carried out using a stepwise
      solid-phase approach based on the Fmoc/t-Bu chemistry, combined with the S
      acetamidomethyl protection for cysteines. The linear, reduced peptide was
      obtained after two reduction steps, using 1,4-dithio-DL-threitol and tri(2
      carboxyethyl)phosphine hydrochloride in basic and acidic conditions,
      respectively. Disulfide bridges were formed by oxidative folding in a
      cystine/cysteine redox buffer, these conditions were found superior to air
      oxidation and to glutathione-catalyzed oxidative folding. The physiochemical and
      enzyme inhibitory properties of synthetic AAI were found identical with those of
      natural product. Several orthogonal protection schemes proved unsuccessful in
      obtaining a biologically active product.

PMID- 9273890
TI  - Random coil conformation for extended polyglutamine stretches in aqueous soluble
      monomeric peptides.
AB  - Several neurodegenerative diseases have been found to be strongly associated with
      proteins containing a polyglutamine stretch which is greatly expanded from
      approximately 20 glutamines in normal individuals to more than 40 in affected
      individuals. A conformational change in the expanded polyglutamine stretch has
      been suggested to form the molecular basis for disease onset. Model peptides
      containing polyglutamine tend to aggregate and become insoluble. We have
      synthesized readily water-soluble monomeric peptides by flanking polyglutamine
      stretches with sequences rich in alanine and lysine. Circular dichroism
      measurements show that polyglutamine stretches of length 9 or 17 adopt a random
      coil configuration in aqueous solution. We think that in the disease-associated
      peptides for normal individuals the stretches of approximately 20 glutamines are
      in a random coil conformation, whereas in affected individuals the polyglutamine
      stretch may be in some other conformation. Our method to design soluble monomeric
      peptides containing extended polyglutamine stretches may be generally useful in
      studying other highly aggregating peptides.

PMID- 9273891
TI  - X-ray studies on crystalline complexes involving amino acids and peptides. XXXII.
      Effect of chirality on ionisation state, stoichiometry and aggregation in the
      complexes of oxalic acid with DL- and L-lysine.
AB  - Crystals of the oxalic acid complex of DL-lysine (triclinic P1; a = 5.540(1), b =
      10.764(2), c = 12.056(2) A, alpha = 77.8(1), beta = 80.6(1), gamma = 75.6(1).; R
      = 4.7% for 2023 observed reflections) contain lysine and semioxalate ions in the
      1:1 ratio, whereas the ratio of lysine and semioxalate/oxalate ions is 2:3 in the
      crystals of the L-lysine complex (monoclinic P2(1); alpha = 4.906(1), b =
      20.145(4), c = 12.455(1) A, beta = 92.5(1).; R = 4.4% for 1494 observed
      reflections). The amino acid molecule in the L-lysine complex has an unusual
      ionisation state with positively charged alpha- and side-chain amino groups and a
      neutral carboxyl group. The unlike molecules aggregate into separate alternating
      layers in the DL-lysine complex in a manner similar to that observed in several
      of the amino acid complexes. The L-lysine complex exhibits a new aggregation
      pattern which cannot be easily explained in terms of planar features, thus
      emphasizing the fundamental dependence of aggregation on molecular
      characteristics. Despite the differences in stoichiometry, ionisation state and
      long-range aggregation patterns, the basic element of aggregation in the two
      complexes exhibits considerable similarity.

PMID- 9273892
TI  - Antimicrobial and hemolytic activities of crabrolin, a 13-residue peptide from
      the venom of the European hornet, Vespa crabro, and its analogs.
AB  - The venom of insects like bee, hornet and wasp contain peptides that exhibit
      potent biological activities. Many of these peptides are composed of 13-26
      residues and are thus accessible through chemical synthesis as well as amenable
      to studies directed toward structure-function correlations. In this report, we
      describe antibacterial and hemolytic activities of crabrolin: FLPLILRKIVTAL-NH2,
      a 13-residue-peptide present in the venom of the hornet Vespa crabro and related
      peptides. The analogs were chosen so that the role of proline and positively
      charged amino acids in modulating biological activities could be evaluated. Our
      results indicate that, although helical conformation is necessary for hemolytic
      activity, it is not a prerequisite for antibacterial activity. Appropriately
      positioned, charged and hydrophobic residues and overall hydrophobicity appear to
      determine antibacterial activity. The discovery of a large number of host-defense
      peptides in a variety of species in recent years offers a large repertoire of
      molecules that can be "engineered" based on biophysical principles to yield
      molecules with specific activities.

PMID- 9273893
TI  - Destruxin analogs: variations of the alpha-hydroxy acid side chain.
AB  - This work describes the synthesis of three destruxin E cyclodepsipeptidic
      analogs. These compounds have an identical amino acid sequence but differ by the
      nature of the hydroxy acid residue with is 2-hydroxy-3-phenylpropionic (Hpp), 2
      hydroxy-5-trimethylsilyl-4-pentynoic (Hpy-TMS) and 2-hydroxy-4-pentynoic (Hpy)
      acid, respectively. The insecticidal properties on the Galleria mellonella larvae
      (paralysis and lethal effect) of these analogs are presented in comparison with
      the natural destruxin E. All these compounds have toxic effects, the most potent
      being Hpy that induces the same effect as destruxin E.

PMID- 9273894
TI  - Solid-phase peptide synthesis at elevated temperatures: a search for and
      optimized synthesis condition of unsulfated cholecystokinin-12.
AB  - A systematic investigation of solid-phase peptide synthesis at elevated
      temperatures using the well-known aggregating peptide acyl carrier protein (65
      74) and the unsulfated cholecystokinin-8 as models is presented. The main goal of
      the investigation was the determination of an optimized experimental condition
      for the synthesis of unsulfated cholecystokinin-12. Of the elevated temperatures
      used, 60 degrees C was the most appropriate. The efficiency of N,N'
      diisopropylcarbodiimide/1-hydroxybenzotriazole (DIC/HOBt) in 25% dimethyl
      sulfoxide (DMSO)/toluene at this temperature was similar to that of 2-(1-H
      benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU).
      Interestingly, this coupling reagent was more efficient than TBTU, benzotriazol-1
      yl oxy-tris(dimethylamino)phosphonium and O-(7-azabenzotriazol-1-yl)-1,1,3,3
      tetramethyluronium hexafluorophosphate in N-methylpyrrolidone. 25% DMSO/toluene
      proved to be suitable for the swelling of the resins phenylacetamidomethyl,
      methylbenzhydrylamine, hydroxymethylphenoxy, 4-(benzyloxy)-2',4'
      dimethoxybenzhydrylamine, 4-(2',4'-dimethoxyphenyl-Fmoc-aminomethyl)phenoxy and
      (4-succinylamido-2',2',4'-trimethoxy)benzhydrylamine. Those polymeric supports
      were fully compatible with the approach. Under the optimized synthesis condition
      found in these studies (temperature of 60 degrees C, DIC/HOBt as coupling reagent
      and 25% DMSO/toluene as solvent), no difficulties related to the aggregation
      phenomenon were encountered. These data confirm the usefulness of solid-phase
      peptide synthesis at elevated temperatures and extend its applicability.

PMID- 9273895
TI  - New renin inhibitors containing novel analogues of statine.
AB  - Solid-phase methodology has been used to synthesize a series of peptides based on
      the N-terminal sequence of human angiotensinogen in which statine (Sta) or the
      novel analogues (3S,4S)-3,4-diamino- or (3R,4S)-3,4-diamino-6-methylheptanoic
      acid (Ads or R-Ads) and (3S,4S)-4-amino-3-aminomethyl- or (3R,4S)-4-amino-3
      aminomethyl-6-methylheptanoic acid (Amd or R-Amd) replace either residue 10 or
      both residues 10-11 at the P1-P1' cleavage site. The synthesis of these novel
      analogues of statine together with biological results on the inhibition of human
      and rat renin by peptides derived from them is reported. The absolute
      stereochemistry of the (3S,4S) Ads was determined by an X-ray crystallographic
      analysis of its N gamma-Boc, B beta-Z, R(+)-1-methyl benzamide derivative.
      Peptide Boc-His-Pro-Phe-His-Sta-Val-Ile-His-NH2 (VI) is the best inhibitor of
      human renin containing Sta at position 10. However, peptides containing Ads and
      Amd gave better rat renin inhibitors than the corresponding Sta-containing
      peptides. Peptides Boc-His-Pro-Phe-His-Ads-Val-Ile-His-NH2 (VII) having Ads at
      position 10 had an IC50 of 12 nM against rat renin. Although Sta has come to be
      accepted as an isosteric replacement for a dipeptide unit rather than for a
      single amino acid residue, in our series of inhibitors Sta is more effective when
      replacing only the amino acid at position 10 in the natural angiotensinogen
      sequence. None of the peptides gave any effect in vivo in a hypertensive rat
      model.

PMID- 9273896
TI  - Structural studies by 1H NMR of a prototypic alpha-helical peptide
      (LYQELQKLTQTLK) and homologs in trifluoroethanol/water and on sodium dodecyl
      sulfate micelles.
AB  - The 1H NMR-determined structure and dynamics of a synthetic, amphiphilic alpha
      helical peptide, PH-1.0 (LYQELQKLTQTLK), and several homologs were compared in
      50% trifluoroethanol-d2 (TFE-d2)/H20 and in sodium dodecyl-d25 sulfate (SDS-d25)
      micelles. The peptides were designed to test the influence on secondary structure
      of placement of favored and disfavored residues relative to a "longitudinal,
      hydrophobic strip-of-helix" defined by the repeating leucines. PH-1.0 was highly
      ordered as an alpha-helix in 50% TFE-d2/H20 and in SDS-d25 micelles. Homologs PH
      1.1, in which L1 was replaced by T, and PH-1,4, in which L12 was replaced by T.
      were found to be partially helical in both media. Calculated structures in SDS
      d25 revealed that the helix of PH-1.1 was slightly disordered at the N-terminus,
      but that of PH-1.4 was completely disordered at the C-terminus. Examination of
      distributions of hydrophobic residues in protein structures revealed that, when
      [symbol: see text] = LIVFM and [symbol: see text] = nonLIVFM, the pattern
      [symbol: see text] is favored and [symbol: see text] is disfavored in alpha
      helices. Several analogs of PH-1.0 incorporating these patterns were studied.
      Peptide PH-1.12 (LYQELQKLLQTLK) retained alpha-helical structure in both 50% TFE
      d2/H20 and in SDS-d25 micelles. However, although PH-1.13 (LYQELQKLTLTLK) was
      fully helical in 50% TFE, it was helical only through residue 6 in SDS micelles.
      Two homologs containing an additional loop of the helix and repeats of favored
      (PH-5.0, NYLQTLLETLKTLLQK) or suppressed LL patterns (PH-5.11, NYLQTLETLKLTQK)
      gave similar results, i.e. the latter peptide was helical only through residue 6
      in SDS micelles. The degree of local order in these SDS micelle-adsorbed peptides
      correlates to placement of hydrophobic residues in motifs which are favored or
      disfavored in proteins in general and in alpha-helices specifically.

PMID- 9273897
TI  - Oxidized and phosphorylated synthetic peptides corresponding to the second and
      third tubulin-binding repeats of the tau protein reveal structural features of
      paired helical filament assembly.
AB  - The microtubule-associated protein tau of normal brains is attached to tubulin
      through its 18-amino-acid repeat units. In the paired helical filaments (PHF) of
      Alzheimer's disease, however, tau is oligomerized in an abnormally
      hyperphosphorylated from (PHF-tau). tau contains two cysteine residues in repeat
      units 2 and 3, but only the R3-R3 homodimer is present in PHF-tau. A serine
      residue two amino acids downstream of the R3 cysteine is a major phosphate
      acceptor site for protein kinase C. In the work repeated here, we used synthetic
      peptides corresponding to R2, R3 and phosphorylated R3 to determine the binding
      of the tau repeat peptides to a peptide fragment corresponding to the C-terminal
      domain of beta-tubulin and to study the kinetics of homo- and heterodimer
      formation. Additionally, we studied two major biochemical properties of the
      peptides that distinguish between normal tau and PHF-tau: conformation and
      metabolic stability. All R2 and R3 peptides bound specifically to the tubulin
      peptide regardless of the state of phosphorylation or dimerization. The reverse
      turn conformation of the tau repeat peptides in the presence of the tubulin
      peptide remained unaffected. Phosphorylation slightly loosened the turn structure
      of the monomeric and dimeric peptides, and did not univocally affect the serum
      stability of the peptides or the ability of the peptides to form dimers. The
      isolated R2 and R3 units formed homodimers approximately in the same rate. When
      the two peptides were mixed, however, the R2-R3 heterodimer was formed
      preferentially over the homodimers. The dimers were generally more stable in
      human serum than the monomers. Our results with the synthetic peptide fragments
      of tau indicate that neither oxidation nor phosphorylation of the repeat units is
      able to generate extended structure such as that found in PHF-tau. Additionally,
      phosphorylation of Ser324 does not appear to modulate the kinetics of
      oligomerization of tau, and in general biochemistry terms, does not affect
      disulfide bridge formation nearby. In agreement with studies at the full-protein
      level, the formation of homodimers of the peptides, a model of the self
      association of tau, is not preferred. If the dimers are formed, however, their
      clearance is considerably slower than that of the monomers, explaining the
      remarkable protease resistance of PHF-tau in the affected brains.

PMID- 9273898
TI  - The solid-phase synthesis of side-chain-phosphorylated peptide-4-nitroanilides.
AB  - Peptide-4-nitroanilides can be quickly synthesised using an Fmoc-based approach
      on 2-chlorotritylchloride resin. Preformed building blocks Fmoc-Xaa-NH-Np (Xaa =
      Cit, Cys, Gln, His, Lys, Orn, Ser, Thr, Tyr, Trp) can be attached via side chain
      to the 2-chlorotritylchloride linker of the resin. N-terminal elongation yields
      the respective peptide-4-nitroanilides after detachment from the solid support.
      We synthesised a set of tetrapeptide-4-nitroanilides with the general structure
      Suc-Ala-Phe-Pro-Xaa-NH-Np (Xaa = Asp, Cit, Cys, Glu, Gln, His, Lys, Orn, Ser,
      Thr, Tyr, Trp). Even peptidyl-arginine-4-nitroanilides are available by a
      slightly modified procedure. First, the appropriate ornithine-containing peptide
      was synthesised. After detachment of the peptide from the resin the side-chain
      primary amino group was transformed to the guanidino function of arginine using 1
      guanyl-3,5-dimethylpyrazole. A further application of this method is the
      convenient synthesis of phosphorylated peptide-4-nitroanilides. Five
      phosphopeptides with the general structure Ac-Ala-Xaa(PO3H2)-Pro-Yaa-NH-Np (Xaa =
      Ser, Thr, Tyr; Yaa = Tyr, Lys) and their nonphosphorylated analogues were
      prepared. Global phosphorylation was carried out on the resin-bound peptides
      using dibenzyl-N, N-diisopropyl-phosphoramidite/tetrazole followed by oxidation
      with tert-butyl hydroperoxide.

PMID- 9273899
TI  - Gene transfer into nerve and muscle by isolated limb perfusion or during
      replantation.
AB  - In this study, the authors tested the feasibility of adenovirus vectors
      transferring functional genetic material into relevent soft-tissue structures
      during replantation of mouse hindlimbs. An adenovirus vector was constructed
      encoding the marker gene LacZ and CMV promoter and titered by plaque forming
      assay to 5 x 10(9) particles/ml. C3H mouse hindlimbs were divided into three
      groups. In Group 1 (n = 9), the femoral neurovascular bundle was divided and re
      anastomosed . Group 2 (n = 9) hindlimbs were transected at mid-femur, perfused
      with adenovirus, and replanted. Group 3 limbs (n = 4) were perfused with saline
      only, followed by replantation. After 48 hr, morbidity and mortality were
      assessed, and the replanted limbs were assayed for gene transfer by
      histochemistry and polymerase chain reaction. 12/18 limbs were viable after 48
      hr. Histochemical staining for adenovirus-mediated LacZ expression was positive
      within skeletal muscle, femoral nerve, and capillaries adjacent to the
      anastomoses. Distal muscle was also gene transfer positive. PCR analysis
      confirmed adenovirus-mediated gene transfer within the femoral nerve and skeletal
      muscle. This study confirms that viral-mediated gene transfer can be accomplished
      into the soft tissues of a replanted extremity.

PMID- 9273901
TI  - Serratus anterior free-tissue transfer: harvest-related morbidity in 34
      consecutive cases and a review of the literature.
AB  - Donor-site morbidity in serratus anterior free-tissue transfers is investigated
      in 34 consecutive cases. Nineteen lower-extremity reconstructions and 15 facial
      reconstructions were retrospectively analyzed. office and hospital charts were
      reviewed, and patients were given a follow-up questionnaire. The mean operative
      time was 6.3 hr and the mean estimated blood loss was 441 cc. Transfusion was
      required in 24 percent of cases. The early complication rate was 21 percent
      consisting of 6 percent hematomas and 15 percent seromas. Scar appearance, pain,
      numbness, and shoulder strength and mobility were acceptable. Scapular winging
      was detectable in 3/9 patients examined, but symptomatic in only one. The number
      of muscle slips harvested or whether the graft was innervated did not
      significantly affect this rate. Half of the patients had returned to work or
      school. None attributed any work disability to their donor sites. They
      participated in many athletic activities, including those requiring upper
      extremity strength and dexterity. Previously reported series are discussed, and
      the morbidity of this donor site is compared with reported series of other free
      muscle flaps. The authors find this flap useful for facial reanimation and for
      soft-tissue coverage with minimal bulk. Low rates of operative, perioperative,
      and long-term morbidity are definite advantages.

PMID- 9273900
TI  - The effect of ammonium sulfate injection on peripheral nerve.
AB  - Local anesthetic drugs with prolonged nerve-block effect would have clinical
      application for postoperative or neuromatous pain relief. This study evaluated
      the possibility of peripheral nerve neurotoxicity by injection of 10 percent
      ammonium sulfate. Both intrafascicular and extrafascicular injection of 10
      percent ammonium sulfate were tested in the rat sciatic nerve model. One percent
      lidocaine HCl, 5 percent phenol, and normal saline were similarly injected for
      comparison. Using histologic studies and motor function evaluation with walking
      track analysis, 10 percent ammonium sulfate was found to be neurotoxic when it is
      injected intrafascicularly; however, extrafascicular injection of this drug did
      not cause significant nerve injury. The neurotoxicity of the 10 percent ammonium
      sulfate solution was intermediate between the neurotoxicity of 0.1 percent
      lidocaine hydrochloride and the marked neurotoxicity of 5 percent phenol
      solution.

PMID- 9273903
TI  - Vascular compliance and vasoconstrictive reactions in rat hindlimbs: comparison
      between storage temperatures of -1 degree C and 4 degrees C.
AB  - The vascular compliance and contractility of vascular smooth muscle of rat
      freshly amputated hindlimbs and hindlimbs preserved at -1 degree C for 12, 24,
      48, and 72 hr were evaluated using a fresh blood extracorporeal circulatory
      system. Vascular compliance was measured under physiologic circulatory conditions
      (blood pressure of the amputated limb was maintained at 80 to 150 mmHg). Vascular
      compliance after storage at -1 degree C for 12 hr or longer decreased
      significantly from that of freshly amputated limbs (p < 0.01). To evaluate the
      contractility of vascular smooth muscle, the arterial blood pressure in the
      amputated limbs was transiently increased with injections of norepinephrine. The
      contractility after storage at -1 degree C for up to 24 hr was not different from
      that of freshly amputated limbs. However, it decreased significantly after 48 hr
      or longer. A comparison of these results with an earlier study that used
      identical methods to investigate limbs preserved at 4 degrees C suggested that
      storage at -1 degree C was inferior to that at 4 degrees C with respect to
      vascular compliance, but was superior to storage at 4 degrees C with respect to
      smooth muscle contractility.

PMID- 9273902
TI  - Long-term results of toe transfer: retrospective analysis.
AB  - Between February 1966 and February 1994, 400 cases of toe transplantation were
      analyzed, to evaluate toe-transfer procedures in thumb and finger reconstruction.
      Techniques utilized included single second-toe transfer, with and without the
      metatarsophalangeal joint (299): second- and third-toe transfer (28); second-toe
      and third proximal phalanx transfer (1); second-toe with flap transfers (66); and
      hallux nail flap with second toe or second and third toe transfer (6). There was
      a survival rate of 96.5 percent, with 386 cases surviving and 14 failing. A more
      than 2-year follow-up was possible in 240 cases. Excellent motor and sensory
      function (more than 90 percent of normal) was achieved in the reconstructed
      fingers and thumbs, as well as satisfactory function (between 86 and 91 percent
      of normal) in the donor foot.

PMID- 9273904
TI  - Drug-induced vasodilation: the effects of sodium nitroprusside, hydralazine, and
      cromakalin on the rabbit carotid artery: in vitro and in vivo study.
AB  - Extreme arterial and venous constructions are common problems in microvascular
      surgery, often leading to tissue injury and flap failure. The ideal pharmacologic
      tool to counteract ischemia should exert its action both locally and distally in
      the microcirculation of the flap. In this study, the vascular properties of
      sodium nitroprusside, hydralazine, and cromakalin were evaluated and compared in
      in vitro and in vivo models in the rabbit carotid artery. In the in vitro study,
      20 rings from the rabbit carotid artery were bathed in Krebs-Ringers solution,
      stretched progressively to an optimal tension of 3.7 to 4.2 gm, and their
      isometric contractile activity was measured. The specimens were precontracted
      with norepinephrine (1 microM) and a dose-response curve was established by
      adding cumulatively either sodium nitroprusside (n = 7), cromokalin (n = 7), or
      hydralazine (n = 7) at increasing concentrations. In the in vivo study,
      microvascular anastomoses were performed bilaterally in the rabbit carotid artery
      in 19 animals using 9-0 nylon suture and standard microsurgical techniques. In
      each animal, one side was treated with heparinized sodium chloride, and served as
      control. The other side was treated blindly with the topical application of 1 ml
      of either sodium nitroprusside (10 mg/ml, n = 5), hydralazine (20 mg/ml, n = 5),
      or cromakalin (25 mg/ml, n = 4), during and after the anastomoses. Blood-flow
      changes in the vessels were continuously monitored with the transonic Doppler
      applied to both carotid arteries for 60 min after the procedure. Sodium
      nitroprusside and cromakalin elicited a concentration-dependent relaxation of
      norepinephrine-precontracted carotid artery rings in vitro. Sodium nitroprusside
      was significantly more effective than cromakalin in inducing relaxation.
      Hydralazine elicited a biphasic response, with low concentrations (1.5 x 10(-5)
      to 1.5 x 10(-3) M) potentiating the norepinephrine-induced contraction, and high
      concentrations relieving this contraction. Microsurgical anastomosis in the
      rabbit carotid artery-produced a significant decrease of blood flow through the
      vessel as measured by the transonic Doppler for 30 min. Topical application of
      heparinized saline did not significantly change the blood flow after the
      microvascular anastomosis. Topical application of sodium nitroprusside and
      cromakalin significantly increased the blood flow in the vessel after the
      anastomosis; however, the topical hydralazine did not significantly alter blood
      flow, but demonstrated a trend toward increased flow values. The data support the
      conclusion that sodium nitroprusside and cromakalin could be used to relieve
      vascular constriction. It is suggested that further studies on the clinical use
      of these drugs in microsurgery is warranted.

PMID- 9273905
TI  - Late results after microvascular reconstruction of severe crush and avulsion
      injuries of the upper extremity.
AB  - From 1978 to 1985, a total of 64 patients underwent successful hand and digit
      replantation/revascularisation for salvage after crush and avulsion trauma to
      their upper extremities. Forty-seven of them (39 males and 8 females) were
      followed between 10 and 17 years (mean: 12.6 years). The average age was 33.2
      years. In 39 patients, replantations were performed: 37 digits (including seven
      thumbs), two hands, and three midhands. Eight patients underwent
      revascularizations in cases of subtotal amputations: two in the midhand, three at
      the wrist, and three at the lower arm. Concomitant injury to the hand or forearm
      was a feature of all cases. In 45 percent of the study population, secondary
      reconstructions were necessary. Outcomes were evaluated using Chen's
      classification (1981) and showed that 19 percent of the patients were classified
      grade 1, 49 percent grade II, 28 percent grade III, and 4 percent grade IV.
      Results demonstrated a greater patient age in the grade III group, and relatively
      more secondary operations in the grade IV patients.

PMID- 9273906
TI  - Lower-limb salvage in a patient with recalcitrant venous ulcerations.
AB  - The authors report the salvage of a lower limb with recalcitrant venous stasis
      ulcers by "sequential" free flaps in a patient with co-existing chronic venous
      insufficiency and arterial occlusive disease. This presentation is interesting
      for inclusion of the following: (1) treatment of a recalcitrant venous ulcer by
      the combination of free-tissue transfer and valvular transplantation; (2)
      thrombosis of the free flap pedicle at an indeterminate time postoperatively
      without flap loss or leg ischemia; and (3) performance of a second free flap to
      the peroneal artery-only, to a one-vessel leg with an excellent clinical outcome
      at long-term follow-up.

PMID- 9273907
TI  - Endothelin-1 does not contribute to ischemia/reperfusion-induced vasoconstriction
      in skeletal muscle.
AB  - The experiment reported was designed to investigate whether endothelin-1 (ET-1)
      contributes to vasospasm and poor perfusion during the reperfusion after
      prolonged ischemia in skeletal muscle. Male Sprague-Dawley rats weighting 100 to
      120 g were anesthetized with Nembutal. The vascular isolated rat cremaster
      muscle, coupled with local interarterial infusion, was the model used in this
      study. The diameters of feeding arterioles and terminal arterioles were measured
      utilizing intravital microscopy. The number of terminal arterioles with temporary
      cessation of flow were counted in each cremaster. Group 1: ET-dose response (8
      rats)--various concentrations of ET-1 (from 10(-8) M to 10(-5) M) were infused
      into the cremaster to test whether this muscle was responsive to the agent in a
      dose-dependent manner. Group 2: ET-antagonist response (12 rats)--PD-142893, 10(
      4) M (ETab receptor antagonist) plus ET-1 10(-7) M were infused into the
      cremaster to test whether vasospasm caused by exogenous ET-1 could be prevented
      by pretreatment with this specific ETab receptor antagonist. Group 3:
      ischemia/reperfusion response (12 rats)--PD-142893, 10(-4) M was infused into the
      cremaster before ischemia (4 hr warm ischemia) and during reperfusion to test
      whether ETab receptor antagonism was effective in preventing the vasospasm
      associated with ischemia/reperfusion injury. The results from this study show
      that a mixed ETab endothelin antagonist, PD-142893, infused before ischemia and
      during reperfusion at a dose which virtually abolished the vasoconstriction
      produced by a high concentration of exogenous endothelin-1, had no effect on
      ischemia/reperfusion-induced vasoconstriction in this model. These results
      suggest that ET-1 probably does not contribute to the ischemia/reperfusion
      induced vasoconstriction and poor reflow in rat skeletal muscle.

PMID- 9273908
TI  - Alcohol and coronary heart disease risk: implications for public policy.

PMID- 9273909
TI  - Estimated numbers of deaths from coronary heart disease "caused" and "prevented"
      by alcohol: an example from Finland.
AB  - OBJECTIVE: Epidemiological studies show that moderate alcohol consumption rather
      than abstention is associated with a lower risk of coronary heart disease (CHD)
      mortality. Our objective was to adjust established methods for calculating
      attributable fractions to a situation where the risk function is J-shaped and to
      estimate the number of CHD deaths "caused" and "prevented" by alcohol in Finland.
      METHOD: Point estimates of relative risk were obtained by a meta-analysis. They
      were pooled by fitting a nonparametric cubic smoothing spline to the data.
      Alcohol consumption distribution was estimated from survey data (N = 4,818; 2,488
      women). The consequences of various assumptions about changes in alcohol
      consumption distribution on CHD mortality were estimated. The most detailed
      analyses are presented for men aged 30-69. The results for the men and women aged
      30-79 are summarized. RESULTS: Among men aged 30-69, the beneficial effects of
      light to moderate alcohol consumption "prevent" some 400 CHD deaths each year
      which corresponds to 12-14% of the observed CHD deaths. Around 20 CHD deaths are
      "caused" by alcohol consumption exceeding the estimated optimum level. Among men
      aged 70-79 and women aged 30-79, the numbers of CHD deaths "prevented" by alcohol
      consumption were approximately 200 and 100, respectively, whereas there were only
      a few CHD deaths "caused" by alcohol. CONCLUSIONS: Our best estimates suggest
      that approximately one-tenth of the observed number of CHD deaths among middle
      aged men in Finland is "prevented" by alcohol, while the relative effect is
      considerably smaller among older men and all women.

PMID- 9273910
TI  - Prevalence and correlates of alcohol use and DSM-IV alcohol dependence in the
      United States: results of the National Longitudinal Alcohol Epidemiologic Survey.
AB  - OBJECTIVE: The purpose of this study was to present updated estimates of the
      prevalence of, and to examine the correlates of, alcohol use and DSM-IV alcohol
      dependence in a representative sample of the U.S. population. METHODS: This study
      was based on the National Institute on Alcohol Abuse and Alcoholism's National
      Longitudinal Alcohol Epidemiologic Survey (NLAES), a representative sample (N =
      42,862) of the United States population aged 18 years and older. RESULTS: The
      prevalence of lifetime alcohol use was 66.0%, with 44.4% of the respondents
      reporting alcohol use during the past 12 months. Lifetime and 12-month
      prevalences of alcohol dependence were estimated at 13.3% and 4.4%, respectively.
      Men were significantly more likely than women to use alcohol, and alcohol use and
      dependence were much more common among cohorts born after Prohibition and after
      World War II. Members of the youngest cohorts, between the ages of 18 and 24
      years at the time of the interview, were more likely to use drugs, to become
      dependent and to persist in dependence compared to the older cohorts. In
      addition, the conditional probability of dependence among users was greatest in
      Cohort 1 (born between 1968 and 1974) after early adolescence compared to Cohort
      2 (born between 1958 and 1967), despite the finding that the probability of
      lifetime use was lower in Cohort 1 compared to Cohort 2. The sociodemographic
      correlates of first use, onset of dependence and persistence of dependence varied
      as a function of the stage of progression. CONCLUSIONS: Implications of these
      findings are discussed in terms of changes over time in drinking patterns,
      dependence liability and vulnerability among recent alcohol users.

PMID- 9273911
TI  - Alcohol use and reported visits to health professionals: an exploratory study.
AB  - OBJECTIVE: To examine the differences in visits to health care professionals
      between drinkers and nondrinkers, as well as between regular and frequent
      drinkers. METHODS: Multivariate analyses were conducted, using data from a
      population survey (weighted N = 35,246, 53.6% women). Analyses were carried out
      for men and women separately, controlling for the effects of age, health problems
      and psychological well-being. RESULTS: In general, visits to health professionals
      increased with age and number of health problems. Abstainers and former drinkers
      were more likely to visit health care professionals than were current drinkers.
      Former drinkers reported higher number of visits than abstainers for both men and
      women. Among male current drinkers, reported number of visits to health
      professionals appeared to decrease as drinks per day increased. These
      associations, however, were not significant among women. CONCLUSIONS: In light of
      these results, it was suggested that heavier drinkers might take a less
      preventive approach to health than either light or moderate drinkers. More
      research is needed to examine the differences in health behaviors between heavier
      and light/moderate drinkers.

PMID- 9273912
TI  - Association between blood pressure and lifetime drinking patterns in moderate
      drinkers.
AB  - OBJECTIVE: To compare the relationship between blood pressure and recent vs
      lifetime alcohol intake measures in a nonalcoholic cohort using measures that
      normalized alcohol intake in terms of the volume of distribution for ethanol
      (total body water) for each subject. METHOD: Correlations between blood pressure
      and alcohol intake measures were determined in a cohort of 84 (48 male)
      normotensive moderate drinkers, using multiple linear regressions to correct for
      the influence of potentially confounding variables. RESULTS: Significant
      correlations were observed between systolic pressure and measures of both recent
      and lifetime alcohol consumption in men. Diastolic pressure was found to be
      significantly associated only with the duration of lifetime drinking, and only in
      women. Measures of lifetime total dose were not significantly correlated with
      either systolic or diastolic pressure. Alcohol intake expressed in terms of the
      number of "drinks" per drinking day was as highly associated with blood pressure
      (systolic) in men as were measures that normalized alcohol intake in terms of the
      body water content of each subject. A measure of the mean number of drinks
      consumed on drinking occasions over the drinking career produced the highest
      correlations with systolic pressure. CONCLUSIONS: Measures of both recent and
      lifetime alcohol intake may be relevant to the understanding of alcohol-blood
      pressure relationships.

PMID- 9273913
TI  - Are the recent trends in liver cirrhosis mortality affected by the changes in
      alcohol consumption? Analysis of latency period in European countries.
AB  - OBJECTIVE: A striking reduction of alcohol-related problems, such as liver
      cirrhosis death rates, has been observed in many western countries in recent
      years. It might be expected that these declines are accompanied by a lagged
      reduction in per capita alcohol consumption, since many years of intake are
      required for cirrhosis of the liver to develop (lag theory). The main aim of this
      study is to verify the validity of the lag theory, taking as target populations
      those resident in European countries. METHOD: Changes in liver cirrhosis death
      rates in 22 European countries between 1970 and 1089 were regressed onto changes
      in per capita alcohol consumption (1961-89) to evaluate the latency period
      between trends of these variables. RESULTS: Eastern countries had a latency
      period between trends in alcohol consumption and in mortality rates of many
      years, whereas in northern, western and southern Europe cirrhosis mortality rates
      were explained by their relationship with per capita alcohol consumption, which
      lagged a few years. In some countries, an immediate contemporary appearance of
      the two phenomena was observed. CONCLUSIONS: These results suggest that the lag
      theory cannot fully explain the relationship between changing alcohol consumption
      and cirrhosis mortality and that other factors, such as alcoholism treatment
      rates, are involved in the wide geographical variability of the latency periods.

PMID- 9273914
TI  - Drunk or sober? Learned conformity to a behavioral standard.
AB  - OBJECTIVE: This research tested the hypothesis that behavioral standards in a
      drinking situation are learned. METHOD: Two groups of male social drinkers (N =
      12) were reinforced with verbal feedback (FB) for matching either a "sober" (S)
      or an "intoxicated" (I) behavioral standard under repeated doses (0.62 g/kg) of
      alcohol. The criterion measure was time to perform a trial on a psychomotor
      tracking task. A fast, efficient time (115 seconds) defined the S standard. A
      slow, inefficient time (150 seconds) defined the I standard. The behavioral
      effect of standards was tested during a final FB training session under alcohol,
      and during retention under a placebo and under alcohol, with FB absent. RESULTS:
      S and I groups approximated their respective standards when reinforced, and these
      standards were retained when reinforcement was subsequently withheld. Under
      placebo, group S displayed sober performance comparable to their drug-free
      baseline, whereas Group I's performance was significantly impaired. These group
      differences remained significant under alcohol, and the drug effect impaired each
      group's performance to a similar degree. CONCLUSIONS: Prior reinforcement of a
      standard under alcohol can lead to the display of that standard when alcohol is
      expected or received. The consistent difference in the groups' performance under
      placebo and under alcohol suggests that learned standards may add an effect on
      behavior in a drinking situation that is distinct from the drug effect. Retention
      of group standards under alcohol in the absence of reinforcement confirms that
      these standards were learned and were not simply a response to situational
      demand.

PMID- 9273915
TI  - Models of alcohol use by young adults: an examination of various attitude
      behavior theories.
AB  - OBJECTIVE: The aim of this study was to test the effectiveness of various
      attitude-behavior theories in explaining alcohol use among young adults. The
      theory of reasoned action (TRA), the theory of planned behavior and an extension
      of the TRA that incorporates past behavior were compared by the method of maximum
      likelihood estimation, as implemented in LISREL for Windows 8.12. METHOD:
      Respondents consisted of 122 university students (82 female) who were questioned
      about their attitudes, subjective norms, perceived behavioral control, past
      behavior and intentions relating to drinking behavior. Students received course
      credit for their participation in the research. RESULTS: Overall, the results
      suggest that the extension of the theory of reasoned action which incorporates
      past behavior provides the best fit to the data. For these young adults, their
      intentions to drink alcohol were predicted by their past behavior as well as
      their perceptions of what important others think they should do (subjective
      norm). CONCLUSIONS: The main conclusions drawn from the research concern the
      importance of focusing on normative influences and past behavior in explaining
      young adult alcohol use. Issues regarding the relative merit of various
      alternative models and the need for greater clarity in the measure of attitudes
      are also discussed.

PMID- 9273916
TI  - Confirmatory analyses of three scoring systems for the 90-item Alcohol Expectancy
      Questionnaire.
AB  - OBJECTIVE: The Alcohol Expectancy Questionnaire (AEQ) is a widely used instrument
      in the field of alcohol research, and several different versions and scoring
      systems for the AEQ are in current use. Two previous confirmatory factor analytic
      studies failed to provide support for two of the present scoring systems for the
      AEQ, but these studies' results may have been an artifact due to the methods
      employed. In this methodological study, three factor structures for the AEQ are
      tested, based on three different models: (1) the original multidimensional model,
      (2) a unidimensional model, and (3) a second-order or hierarchical model. METHOD:
      Data from a previous study provided an effective N of 507 college men and women,
      who completed a self-administered version of the AEQ. RESULTS: Nearly all of the
      models tested clearly did not fit the data. One model, a three-scale scoring
      system, may be cautiously viewed as having demonstrated a marginal fit.
      CONCLUSIONS: Within the context of the present study's limitations, the validity
      of current scoring systems for the AEQ is questionable.

PMID- 9273918
TI  - Legal and social control of alcohol-impaired driving in California: 1983-1994.
AB  - OBJECTIVE: This research was designed to provide information on the legal and
      social forces that influence change in control of alcohol-impaired driving.
      METHOD: Attitudes, perceptions and behaviors concerning drinking and driving for
      California drivers in 1994 (n = 608) were compared to similar information
      collected from California drivers in 1983 and 1986 (n = 291) through random-digit
      dialing telephone interviews. RESULTS: Self-reported drinking-driving violations
      showed a substantial decline, paralleling the well-documented drop in alcohol
      related traffic crashes during this time span. A large reduction in drinking
      before driving was reported for all age groups, men and women, and for both heavy
      drinkers and light drinkers. There was evidence of an increase in the levels of
      both general deterrence and general prevention. Increased external control was
      reflected in greater knowledge of drinking-driving laws and trends toward an
      increased expectation that violations would be followed by unpleasant
      consequences. Strong gains in creating a social norm for control of alcohol
      impaired driving were indicated by perceptions that friends and relatives were
      more likely to disapprove of driving after drinking, observations of more control
      of drinking by drivers at occasions where alcohol is served and an increase in
      the view that it is morally wrong to drive after heavy drinking. CONCLUSIONS:
      California has made substantial progress in efforts to control alcohol-impaired
      driving, through increases in both general deterrence (fear of punishment) and
      general prevention (moral inhibitions and socialization of preventive habits),
      especially the latter.

PMID- 9273917
TI  - Drinking drivers missed at sobriety checkpoints.
AB  - OBJECTIVE: Sobriety checkpoints are an effective deterrent to alcohol-impaired
      driving although a substantial proportion of drinking drivers who pass through
      checkpoints are missed. The present study was designed to determine the extent to
      which police officers correctly identify individuals with blood alcohol
      concentrations (BACs) at or above 0.05% at checkpoints, and if there are
      characteristics of drivers, vehicles or checkpoints that are associated with
      decreased chances of detection. METHOD: To determine which drivers are likely to
      be missed, drivers not detained by police for additional sobriety evaluation were
      interviewed and voluntary breath samples were provided at 156 sobriety
      checkpoints in North Carolina. RESULTS: More than 50% of the drivers with BACs in
      excess of 0.08% and almost 90% of drivers with BACs in excess of 0.05% were not
      detained by officers. For drivers with BACs of 0.05% or higher, women and those
      35 or younger were more likely to be missed than were men and older drivers.
      Drivers without passengers were more likely to be missed than those with
      passengers. Drivers were also more likely to be missed during weekend
      checkpoints. Similar results were found for drivers with BACs at or above 0.08%.
      CONCLUSIONS: Alerting police officers to characteristics of drinking drivers more
      likely to be missed may improve detection rates. In addition, passive alcohol
      sensors could improve the effectiveness and efficiency of sobriety checkpoints in
      detecting drinking drivers.

PMID- 9273919
TI  - A prospective study of the utility of standardized instruments in predicting
      recidivism among first DWI offenders.
AB  - OBJECTIVE: The present study investigated the utility of four instruments--the
      MacAndrews scale of the MMPI-2 (MAC), four scales of the Alcohol Use Inventory
      (AUI), the Michigan Alcoholism Screening Test (MAST) and the Skinner's Trauma
      Scale (STS)--in assessing risk for rearrest among first driving while impaired
      (DWI) offenders. METHOD: Subjects were clients (N = 1,384, 80% male) convicted of
      a DWI offense who were referred to the Lovelace Comprehensive Screening Program
      for evaluation and who completed a court-mandated screening program. Stratified
      life table analysis was used to determine rearrest rates in the period following
      the screening referral. RESULTS: After 4 years of follow-up the overall rearrest
      rate was 21.0%. The best predictors of recidivism were a MAC score of 23 or
      above, elevated scores on AUI scales, young male status (age 30 or under) and
      arrest blood alcohol concentration (BAC) of .200% or above. The best schematic
      for classifying first offenders into risk groups was determined using the risk
      factors above and defined groups with recidivism rates ranging from 13.0% to
      38.8%. CONCLUSIONS: We were able to identify cohorts of first offenders at
      relatively low and high risk for recidivism using a stratified analysis with six
      strata defined from four variables. The MAC was the best, single variable for
      classifying offenders' future recidivism risk, indicating that, in addition to
      evaluating for the presence and severity of alcohol and drug use, screening
      programs for DWI offenders should carefully evaluate personality factors in
      making referral and sentencing recommendations.

PMID- 9273920
TI  - Immediate, quantitative estimation of blood alcohol concentration from saliva.
AB  - OBJECTIVE: Reliable, valid, and noninvasive methods to quantitatively estimate
      blood alcohol concentration (BAC) are important in forensic, work place, medical
      and research settings. To date, noninvasive methods for quantitatively estimating
      BAC have primarily used breath testing. This study evaluated a new device for
      estimating BAC via saliva that is unique in providing on-the-spot, quantitative
      results in 2 minutes. The Q.E.D-A150 test (STC Technologies, Inc., Bethlehem,
      Pa.) is based on the enzymatic oxidation of alcohol by alcohol dehydrogenase.
      Saliva alcohol concentration (SAC) is read directly from the test device. METHOD:
      In each of three sessions, 24 male and 15 female social drinkers, aged 21-28
      years, provided yoked breath and saliva samples prior to, and at five times
      following, a dose of 1.0 g (men) or 0.9 g (women) alcohol per kg lean body mass.
      RESULTS: Intertest reliability, determined by two simultaneous saliva samples,
      was very high for each measurement time (r's = .97 to .99), for each subject (4's
      = .95 to .99) and across all observations (r = .98). The coefficient of variation
      was below 5% in 97% of paired observations. The correlation between breath and
      saliva estimates was .94 across all observations and ranged from .92 to .98
      across measurement times. The difference between breath and saliva estimates was
      significantly larger on the ascending limb than on the descending limb of the
      blood alcohol curve at comparable BACs. On the average, SAC estimates were 6
      mg/dl higher than breath during ascending BACs and 3 mg/dl higher than breath
      during descending BACs. Individual differences in the ratio of SAC to breath
      measures of BAC ranged from 0.99 to 1.15 (average = 1.06). Test performance was
      not affected by gender, drinking pattern or cigarette smoker status. CONCLUSIONS:
      The Q.E.D.-A150 device had good reliability and validity for the noninvasive,
      quantitative estimation of BACs.

PMID- 9273921
TI  - Alcohol-related problems among black, Hispanic and white men: the contribution of
      neighborhood poverty.
AB  - OBJECTIVE: We examined the cross-sectional relationships between race/ethnicity,
      neighborhood poverty and alcohol-related problems among black, Hispanic and white
      male drinkers. Test hypotheses were that black and Hispanic men living in more
      impoverished neighborhoods would report increased numbers of alcohol-related
      problems than comparable white men. METHOD: Study hypotheses were tested in a
      sample of 744 black, Hispanic and white men participating in the 1992 National
      Alcohol Follow-up Survey. Study hypotheses were analyzed using generalized linear
      model regression analysis. RESULTS: Neighborhood poverty had a greater effect on
      alcohol-related problems in black than in white men, partially supporting our
      hypothesis. Black men living in more impoverished neighborhoods reported greater
      numbers of alcohol-related problems than comparable white men; there were no race
      differences among more affluent men. Neighborhood poverty had little effect on
      alcohol-related problems in Hispanic men. CONCLUSIONS: Findings suggest that,
      giving unfavorable economic conditions, black men will report greater numbers of
      alcohol-related problems than comparable white men.

PMID- 9273922
TI  - Mother-son interactions in disruptive and nondisruptive adolescent sons of male
      alcoholics and controls.
AB  - OBJECTIVE: The goal of the study was to describe mother-son relations in
      adolescent sons of male alcoholics. METHOD: Eighty-two mother-son dyads were
      observed interacting in a laboratory setting. They were subdivided into four
      groups: sons of male alcoholics (SOMAs) with and without behavioral problems,
      boys who were not SOMAs but had behavioral problems, and controls. Disruptive
      boys were included and distinguished from SOMAs because while there is often co
      occurrence of these two problems they are not always found in the same
      individual. RESULTS: It was found that the biological mothers of the disruptive
      boys were less supportive and nurturing of their sons than were the other
      mothers. They were also rated as less mature, more anxious, and less confident in
      themselves as parents. There were no significant findings for the SOMAs or their
      mothers, whose interactions resembled the control group. CONCLUSIONS: It is
      possible that sons of male alcoholics' differences may be due to the
      disruptiveness of the boys rather than to their family alcoholic status per se.

PMID- 9273923
TI  - Pathogenic vibrios in the natural aquatic environment.
AB  - In recent years, members belonging to the genus Vibrio of the family Vibrionaceae
      have acquired increasing importance because of the association of several of its
      members with human disease. The most feared of the Vibrio species is Vibrio
      cholerae, the causative agent of cholera, a devastating disease of global
      significance. Other important vibrios of medical importance are V.
      parahemolyticus, V. vulnificus, V. mimicus, and to a lesser extent V. fluvialis,
      V. furnissii, V. hollisae, and V. damsela. Recent studies have also implicated V.
      alginolyticus and V. metschnikovii in human disease, although their complete
      significance has not yet been established. The virulence of all medically
      important vibrios is aided by a variety of traits that help breach human
      defenses. In this review, we provide an overview of the environmental
      distribution of the pathogenic vibrios and the important virulence traits that
      enable them to cause disease.

PMID- 9273924
TI  - Drinking water chlorination by-products and cancer.
AB  - This review discusses the relation between by-products of drinking water
      chlorination and cancer in the light of present toxicological and epidemiologic
      evidence. During the chlorination of drinking water, a complex mixture of by
      products forms from chlorine and the organic and inorganic compounds present in
      raw water. The quality and quantity of such compounds depend on the specific
      nature of the organic material in raw waters, the inorganic material in raw
      water, pH, temperature, other water treatment practices, and the chlorine timing
      and dose added. Chlorination by-products are important mainly when surface water
      is used for drinking water as more organic compounds are present in surface
      waters than in ground waters. The gastrointestinal and urinary tract are the
      cancer sites that are most often associated with the use of chlorinated surface
      water or with the quantity of chlorination by-products in the water-supply
      network. Yet the microbial quality of drinking water should not be compromised by
      excessive caution over the potential long-term effects of disinfection by
      products because the risk of illness and death resulting from exposure to
      pathogens in untreated drinking water may be several orders of magnitude greater
      than the cancer risks from chlorination by-products.

PMID- 9273925
TI  - Potential health risks from indoor exposure to chlorpyrifos (O,O-diethyl O-[3,5,6
      trichloro-2-pyridyl] phosphorothioate).
AB  - A four-season, indoor air quality survey was conducted in Southern Louisiana to
      determine the indoor air levels of the pesticide chlorpyrifos. Gas
      chromatographic analysis of 213 air samples collected from 53 houses revealed
      levels of chlorpyrifos ranging from non-detected to 2.13 micrograms/m3. Using the
      Florida-Pinella exposure guideline (24-hr exposure to chlorpyrifos at 0.48
      microgram/m3), it was noted that 14% of the samples exceeded this guideline. The
      exposure of occupants to the indoor air concentrations of the pesticide, however,
      were below either the irritation or the odor thresholds, and effects on acute and
      chronic health responses remains uncertain.

PMID- 9273926
TI  - The application of ergonomics in the work environment of general surgeons.
AB  - Ergonomics, also called human factors engineering, is the study of the behavior
      and activities of individuals in relation to the working environment and the
      mechanical and electronic equipment operated by the worker. The function of
      specialists in ergonomics is to design or to improve the workplace, equipment,
      and procedures of workers to ensure the safe, healthy, and efficient achievement
      of personal and organizational goals. Many mental and physical similarities can
      be found between the work of a surgeon and the jobs of skilled industrial and
      military personnel. This review addresses the necessity for applying ergonomics
      in surgical working activities. The materials reviewed here are classified into
      the following topics in surgical ergonomics: Visualization, manipulation,
      posture, mental and physical workload, and the operating-room environment. It was
      concluded that the discipline of ergonomics can enhance our understanding of the
      way in which surgeons work. As surgeons confront increasingly complex and costly
      procedures, the need to cut health-care costs deems it necessary to develop a
      scientific understanding of the mechanics of surgical operations.

PMID- 9273927
TI  - Organic mercury: an environmental threat to the health of dietary-exposed
      societies?
AB  - As a natural element, mercury is ubiquitous in the environment. The largest
      amount of mercury, amounting to approximately 100,000 tons per year, originates
      from the degassing of the earth's crust. To this amount, such anthropogenic
      activities as combustion of fossil fuels and releases from industrial activities
      add approximately 20,000 tons of mercury every year. The emitted mercury, both
      natural and anthropogenic, is in an inorganic form, predominantly as the metallic
      vapor (Hgzero). In aquatic environments, however, inorganic mercury is
      microbiologically transformed into the lipophilic organic compound,
      methylmercury. The transformation from the hydrophilic to the lipophilic state
      makes mercury more prone to biomagnification in aquatic food chains.
      Consequently, populations with a traditionally high dietary intake of food
      originating from either fresh-water or marine environments have the highest
      exposure to methylmercury. Because of their traditional pursuit of marine
      mammals, the Inuits belong to the highest dietary exposure group /1/. This
      situation is particularly true for the Polar Eskimos in North West Greenland.
      This population has the most traditional lifestyle among the Inuits and hunts
      predatory species of whales, such as beluga and narwhal, a combination that
      results in a high level of exposure to methylmercury. Polar Eskimos in North West
      Greenland, living in areas with no 'accidental' mercury pollution, but with a
      high dietary access to methylmercury thus exemplify a population group with a
      current potential environmental health problem.

PMID- 9273928
TI  - A clinico-epidemiological study on gastritis in gastric carcinoma and in non
      cancerous gastric pathology in Poland.
AB  - To investigate the risk of gastric cancer development in subjects with atrophic
      and nonatrophic gastritis, we studied 221 consecutive gastric cancer patients and
      7647 non-cancer subjects for whom endoscopic biopsy of the gastric mucosa was
      available. In gastritis patients, the relative risk (RR) estimates of gastric
      cancer were as follows: corpus atrophic gastritis RR = 8.7 (95% CI = 5.4-14.1),
      antral atrophic gastritis RR = 4.5 (2.4-8.1), chronic atrophic pangastritis RR =
      7.6 (3.8-15.3), corpus nonatrophic gastritis RR = 1.6 (0.9-2.7), antral non
      atrophic gastritis RR = 1.2 (0.7-2.3), and pangastritis RR = 1.3 (0.6-2.8). The
      latter was of borderline significance (p = 0.07). In peptic ulcer, a significant
      excess risk was calculated for subjects with either corpus atrophic gastritis (RR
      = 3.1 [2.5-3.9] or antral atrophic gastritis (RR = 3.5 [2.6-4.8]). For stomach
      polyps, the risk was significantly increased only in subjects with corpus
      atrophic gastritis (RR = 2.1 [1.3-3.5]). The risks for both peptic ulcer and
      polyps, however, were significantly increased in chronic atrophic pangastritis. A
      substantial excess risk of gastric cancer was found for atrophy in the corpus (RR
      = 20.9 [9.0-48.9]) and in the antrum (RR = 14.9 [5.3-41.9]). An increased risk of
      peptic ulcer was also confirmed in subjects with atrophy in the corpus (RR = 3.0
      [1.3-6.9]) and in the antrum (RR = 4.9 [2.0-12.1]).

PMID- 9273930
TI  - Normal bone, osteoporosis and the rheumatologist.

PMID- 9273929
TI  - Relation between body height and self-reported myocardial infarction in Germany.
AB  - BACKGROUND: Several studies have reported an association between body height and
      the incidence of myocardial infarction. METHODS: We analyzed data from regional
      and national health surveys that were conducted from 1984-1992 within the
      framework of the German Cardiovascular Prevention Study. Eligible survey
      candidates were males and females with German nationality in the age group 25-69
      years. The total number of subjects in our study comprised 12,447 males and
      13,355 females. The assessment of whether a respondent had ever undergone a
      myocardial infarction was based on self-reporting by the subject. Multiple
      logistic regression analyses, controlling for several confounding factors, were
      carried to calculate odds ratios to estimate th effect of body height on the
      prevalence of self-reported myocardial infarction, comparing each body-height
      quintile with the shortest group, which served as the reference group. RESULTS:
      Without adjusting for confounding variables, a strong association between body
      height and self-reported myocardial infarction was found in both genders (trend
      test: p < 0.001), with an unadjusted odds ratio (OR) of 0.41 for males and 0.33
      for females. After adjusting for age, the ORs increased to 0.67 (p < 0.05) in
      males and 0.58 (p < 0.05) in females for quintile 5 (tallest) compared with
      quintile 1 (shortest). After an additional adjustment for community size, region,
      social class, and number of CVD risk factors, the ORs of myocardial infarction
      for quintile 5 (males OR = 0.78, females OR = 0.68) were higher than those for
      quintile 1, but the results were no longer statistically significant.
      CONCLUSIONS: Despite the lack of statistical significance, we suggest that the
      differences in the prevalence of myocardial infarction for the five height
      quintiles cannot be explained by confounding factors alone. The underlying causes
      for such height-specific differences remain unknown.

PMID- 9273931
TI  - Epidemiology of osteoporosis.

PMID- 9273932
TI  - Pathogenesis of the osteoporoses.

PMID- 9273933
TI  - Interpretation of bone densitometry.

PMID- 9273934
TI  - Practical use of bone densitometry.

PMID- 9273935
TI  - Biochemical markers of bone turnover in osteoporosis.

PMID- 9273936
TI  - The role of bone biopsy in evaluating bone disease.

PMID- 9273937
TI  - Estrogen and the prevention and treatment of osteoporosis.

PMID- 9273938
TI  - Alendronate: preclinical studies.

PMID- 9273939
TI  - Bisphosphonates in the treatment of osteoporosis.

PMID- 9273940
TI  - Calcitonin.

PMID- 9273941
TI  - Fluoride therapy for bone disease.

PMID- 9273942
TI  - Calcium and vitamin D in the prevention and treatment of osteoporosis.

PMID- 9273943
TI  - Prevention of falls in patients with osteoporosis.

PMID- 9273944
TI  - Managing osteoporotic fractures: minimizing pain and disability.

PMID- 9273945
TI  - Osteoporosis in men.

PMID- 9273946
TI  - Glucocorticoid-induced osteoporosis: prevention and treatment.

PMID- 9273947
TI  - Cytokines and the pathophysiology of bone erosions in rheumatoid arthritis.

PMID- 9273948
TI  - Fibrodysplasia ossificans progressiva: why do some people have two skeletons?

PMID- 9273949
TI  - Paget's disease of bone: complications and treatment.

PMID- 9273950
TI  - Is there cyclosporine A-induced bone disease?

PMID- 9273951
TI  - Musculoskeletal manifestations of osteomalacia.

PMID- 9273952
TI  - Renal osteodystrophy.

PMID- 9273954
TI  - Total arterial myocardial revascularization.

PMID- 9273953
TI  - Role of parathyroid hormone-related peptide in hypercalcemia of malignancy and
      the development of osteolytic metastases.

PMID- 9273955
TI  - Death, mode of death, morbidity, and rehospitalization after coronary artery
      bypass grafting in relation to occurrence of and time since a previous myocardial
      infarction.
AB  - To describe the prognosis during 2 years after coronary artery bypass grafting
      (CABG) in relation to occurrence of and time since a previous acute myocardial
      infarction (AMI), data of all patients in western Sweden who underwent CABG
      without simultaneous valve surgery in the period June 1988-June 1991 were
      evaluated. In all, 2120 patients were included in the analyses. Of these, 1296
      (61%) had a history of AMI and 127 (6%) had suffered an AMI within the last month
      before CABG. Mortality during the first 30 days after CABG was for patients with
      no previous AMI, previous AMI > 30 days prior to CABG, and previous AMI < or = 30
      days prior to CABG 2.4%, 4.1%, and 5.5%, respectively (p < 0.05). The
      corresponding figures for the period between 30 days and 2 years after CABG were
      3.6%, 4.4%, and 3.4% respectively (NS). In a multivariate analysis among patients
      with a previous AMI, a recent infarction (< or = 30 days prior to CABG) did not
      turn out as an independent predictor of death during 2 years of follow-up. A
      history of AMI was associated with increased mortality during the first 30 days
      but not thereafter, but recent AMI was not an independent predictor of total 2
      year mortality.

PMID- 9273956
TI  - Late survival and predictors of recurrent angina after coronary artery
      reoperation.
AB  - Although coronary artery reoperations are now well established, there is limited
      information concerning factors predisposing to further recurrent angina after a
      successful second bypass operation. We have retrospectively evaluated the late
      (10-year) results, and identified predictors associated with poor long-term
      outcome, of fifty-seven consecutive patients, mean age 54.8 (SD = 9.7) years,
      range 43 to 67 years, reoperated on for recurrent angina (RA) between January
      1980 and May 1988. Twenty-four factors possibly influencing the probability of
      further recurrence of angina (FRA) were evaluated, comparing operative survivors
      who developed FRA with those who remained symptom-free during a complete follow
      up study period ranging from 35 to 134 months. Reoperative mortality was 8.7%
      [95% confidence limits (95% CL) 6.7 to 11%]. Survival analysis (Kaplan-Meier)
      revealed 94% at 3 (95% CL +/- 7%), 90% at 5 (95% CL +/- 8%) and 83% at 10 years
      (95% CL +/- 12%). Probability of freedom from FRA was 88%, 73%, and 56% at 1, 5,
      and 10 years, respectively. Using univariate analysis, female sex (p < 0.05),
      time between 1st operation and RA (p < 0.005), family history of ischaemic heart
      disease (IHD) (p < 0.01), obesity (p < 0.001), time between 1st and 2nd operation
      (p < 0.001), and the non-use of internal mammary artery at reoperation (p <
      0.0001) were associated with increased incidence of FRA. Independent risk
      factors, by multivariate analysis (Cox's proportional hazards), were: family
      history of IHD (p = 0.006), triple-vessel disease (p = 0.024), obesity (p =
      0.052), and time interval-between 1st and 2nd operation (p = 0.046). We conclude
      that reoperative surgery results in satisfactory long-term survival and angina
      free interval. Patients with a short time interval between reoperations, family
      history of IHD, obesity, triple-vessel disease, and non-use of internal mammary
      artery at reoperation are at higher risk of developing further recurrent angina,
      and, therefore, more likely to require a subsequent revascularisation procedure.

PMID- 9273957
TI  - Heart surgery in patients aged eighty years and above: determinants of morbidity
      and mortality.
AB  - Escalating medical costs, limitation of resources and the necessity to provide
      cost-effective medical care have created a need for systematic risk
      stratification and cost-benefit analyses in the background of an ongoing
      discussion. Results of heart surgery in octogenarians have been evaluated in a
      prospective single-center, study since 1990. 101 consecutive patients (55/ 101 =
      54.5% female) aged 80 years and above (median: 81 years; interquartile range
      [IQR]: 80.0-82.5, total range [TR]: 80-92 years) undergoing open heart surgery at
      our institution between January 1990 and March 1996 were included into this
      prospective study. Prior to surgery, most patients were severely symptomatic
      being in functional NYHA classes either III (56.4%) or IV (31.7%). 61/101 (60.4%)
      patients underwent isolated coronary artery bypass grafting (CABG), 23 (22.8%)
      had aortic valve replacement (AVR), 14 patients (13.9%) had CABG combined with
      AVR or double valve replacement and 3 (3.0%) had mitral valve repair. Follow-up
      (median: 23.0 months. IQR: 10.5-39.0, TR: 1-72) was focused on long-term
      morbidity and quality of life. The impact of preoperative and operative risk
      factors on morbidity and mortality was determined by uni- and multivariate
      statistical analysis. The 30-days overall mortality in this study was 7.9%. The
      postoperative course was uneventful for 27 (26.7%) of our patients. Univariate
      risk factors of postoperative mortality were: left main stem disease (p < or =
      0.044), ejection fraction < 45% (p < or = 0.006), preoperative intensive care
      unit (ICU) (p < or = 0.002), urgent or emergency operation (p < or = 0.034). The
      only independent predictor of operative mortality was preoperative ICU-stay (p <
      or = 0.008). Significant risk factors for the number of postoperative
      complications in the multivariate analysis were: prior stroke (p < or = 0.04),
      diabetes mellitus (p < or = 0.02), New York Heart Association (NYHA) class IV
      symptoms (p < or = 0.002) and prolonged cross-clamping time (p < or = 0.001).
      Mean postoperative length of stay in the ICU was 3.9 +/- 3.9 days. Late morbidity
      was not related to postoperative complications. Cumulative survival was 87.9%,
      79.5% and 72.9% at one, two or five years, respectively. After hospital
      discharge, 67/93 patients (82.8%) were in NYHA functional class I or II. Cardiac
      surgery in very elderly patients can be performed with acceptable operative risk
      and a favorable long-term outcome. The individual patient risk-profile including
      significant co-morbid conditions and severity of the heart disease predicts not
      only survival but the extent of perioperative morbidity.

PMID- 9273958
TI  - Long-term mechanical circulatory support.
AB  - Against the background of an increasing number of patients waiting for heart
      transplantation but a stagnating number of transplant procedures, long-term
      mechanical circulatory support is gaining major importance. We investigated the
      outcome of 20 patients (15 men, and 5 women, aged between 15 and 66 years) each
      supported for more than 100 days between September 1987 and August 1996. The
      indications for implantation were bridging in 17 patients, myocarditis in 2
      patients, and postcardiotomy cardiogenic shock in one patient. 12 patients
      received the Novacor IVAD, 4 patients the Thoratec system, 3 patients the
      HeartMate device and one patient both Novacor and Thoratec. Mean duration of
      support was 178.1 days, 15 patients were transplanted, 14 of them could be
      discharged, 2 patients died, 4 patients are still waiting. The most frequent
      complication was device-related infection in 11 patients. The results have shown
      that all three systems are safe and reliable devices for supporting patients for
      more than 100 days.

PMID- 9273959
TI  - The best site for bronchial stapling in left and right upper lobectomies: a
      comparative study.
AB  - Bronchial stapling and postoperative bronchoscopy was performed in 22 left upper
      lobectomies (LUL) and 18 right upper lobectomies (RUL). Seven LUL cases and 15
      RUL cases with staples positioned 2 bronchial rings (BR) from the entrance to the
      upper lobe bronchus (ULB) had no residual cartilaginous rings at the stump
      (RCRS). Deformity of the residual bronchus (DRB) was found in 6 of these 7 LUL
      cases, and 3 of these 15 RUL cases (p < 0.01), with a high rate of suffering from
      a severe cough. The remaining 15 LUL cases and 3 RUL cases had staples positioned
      3 to 4 BR from the entrance to the ULB resulting in one or two RCRS. Only one LUL
      case with one RCRS was accompanied by DRB and coughing. These facts strongly
      imply a connection between cough and DRB. DRB was frequently seen in LUL cases
      with no RCRS (86%), was less likely to occur in cases with one RCRS (10%), and
      was absent in cases with two RCRS (p < 0.01). We conclude that bronchial staples
      applied during a LUL should be positioned 3 or 4 bronchial rings distal from the
      entrance to the left ULB.

PMID- 9273960
TI  - Cardiac surgery in Germany during 1996. A report by the German Society for
      Thoracic and Cardiovascular Surgery.

PMID- 9273961
TI  - The omental flap with skin grafting for treatment of a difficult sternal closure.
AB  - A case report of difficult sternal closure is described. Chest closure following
      cardiac operation in critically ill patients can be a problem. Techniques have
      been described so that sternal closure can be delayed until the patient is
      hemodynamically stable and hemostasis has been achieved. However, in some
      instances, the sternal closure can not be performed because of prolonged
      cardiopulmonary instability. We describe the use of transposition of an omental
      flap with skin grafting in a 74-year-old patient with aortic valve stenosis, poor
      pulmonary function, and a thoracic deformity. This technique enabled incomplete
      sternal closure which maintained hemodynamic stability.

PMID- 9273962
TI  - Mediastinal tuberculous lymphadenitis diagnosed and treated by thoracoscopy.
AB  - Mediastinal tuberculous lymphadenitis is a relatively rare disorder and it is
      sometimes hard to identify the acid-fast bacilli involved or its specific
      pathological findings. We employed thoracoscopy to obtain diagnostic material
      from a 25-year-old woman with a newly-appearing mediastinal mass despite
      antituberculous therapy for cervical tuberculous lymphadenitis. Thoracoscopy also
      proved effective in the curative surgical procedure, i.e. resection of the
      abscess wall as far as possible, debridement of the remaining wall, irrigation,
      and instillation of streptomycin into the abscess and thoracic cavity.
      Postoperatively the patient has followed a favorable course for one year.

PMID- 9273963
TI  - Aortotracheal fistula: demonstration by computerized tomography.
AB  - Aortotracheal fistula is a rare condition that is invariably fatal if not
      diagnosed and surgically treated. Patients usually present with small
      intermittent haemoptysis. In cases of aortotracheal fistula bronchoscopy may be
      both misleading and dangerous. The findings using computerized tomography (CT)
      are usually non-diagnostic. We present a case of aortotracheal fistula in which
      CT established the diagnosis by demonstrating the fistula as a continuous tract
      between the aorta and the trachea. CT should be considered in the initial
      investigation of patients suspected to have such a disease.

PMID- 9273964
TI  - Omentopexy for anastomotic dehiscence after tracheal sleeve pneumonectomy.
AB  - A 54-year-old male patient developed anastomotic dehiscence following tracheal
      sleeve pneumonectomy for squamous-cell carcinoma of the right lung. Among various
      possible methods of treatment, omentopexy was adopted and proved very effective
      in the treatment of such a fatal complication.

PMID- 9273965
TI  - Unsuccessful omentopexy in thoracic surgery.
AB  - Omentopexy has improved the treatment of chronic empyema and postpneumonectomy
      bronchopleural fistula, which otherwise are difficult to manage. However,
      omentopexy is not effective in some patients. Four of 17 patients who underwent
      omentopexy in our institution between January 1978 and March 1994 did not respond
      to the treatment and died. In two patients, a dead space remained after surgery
      and there was insufficient sterilization. In one patient, a dead space appeared
      after surgery and it was impossible to control infection. The fourth patient had
      dehiscence of the anastomosis triggered by postoperative acute gastritis. All
      four patients in whom omentopexy was not successful died. When omentopexy is used
      for empyema, the space should first be sterilized. If sterilization is
      insufficient, muscle filling and thoracoplasty must be performed and no dead
      space left.

PMID- 9273966
TI  - Surgical treatment of left-atrial myxoma in Carney's complex.
AB  - Although rare, cardiac myxomas are the most frequently encountered primary
      neoplasms of the heart. Cardiac myxomas are typically sporadic, benign, non
      recurrent tumors, and they are usually seen in the left atrium. Patients who have
      myxoma-associated spotty pigmented skin lesions, endocrine neoplasms with
      overactivity, and noncardiac myxomatous tumors are said to have Carney's complex.
      This report presents a 21-year-old woman with Carney's complex. She was operated
      for tetralogy of Fallot and total correction was performed at another center when
      she was three years old. Two years ago, she was operated on for a primary
      pigmented nodular adrenocortical tumor and bilateral adrenalectomy was performed.
      Her present admission to our clinic was for left-atrial myxoma with associated
      symptoms. Patients with Carney's complex have distinctive clinical features which
      separate them from the larger group of patients with the more common sporadic
      myxoma. The most important distinction is that the myxoma syndrome appears to be
      a multisystem disease.

PMID- 9273967
TI  - Fibrous tissue overgrowth and prosthetic valve endocarditis: report of a case.
AB  - Mechanical valve stenosis without restricted occluder motion and paravaluvular
      leakage developed in a patient who had undergone patch closure of partial
      atrioventricular septal defect and replacement of the left atrioventricular valve
      13 years previously. Dense calcification of the supravalvular region was shown in
      a cineradiogram, whereas transthoracic and transesophageal echocardiography
      failed to reveal any obstructive mechanism. Elevated transprosthetic pressure
      gradient with unrestricted occluder motion suggested prosthetic valve stenosis
      resulting from fibrous tissue overgrowth, although this was not visualized by the
      modern diagnostic imaging tools. Reoperation confirmed calcified fibrous tissue
      overgrowth obstructing the mechanical valve inflow. Examination of resected
      tissue revealed prosthetic valve endocarditis due to alpha-streptococcus.
      Paravalvular leakage accompanying fibrous tissue overgrowth may indicate the
      presence of prosthetic valve infection even if the clinical manifestations are
      scarce.

PMID- 9273968
TI  - A rare case of mixed type total anomalous pulmonary venous connection and its
      surgical treatment.
AB  - In the mixed types of total anomalous pulmonary venous connection, pulmonary
      veins frequently show an opening at the supracardiac and cardiac level. Rarely,
      some other combinations of mixed type cases have been reported in the literature.
      In the present case the right and left pulmonary veins formed two distinct venous
      chambers and showed supracardiac and infracardiac openings. Anastomosis of each
      of these common venous chambers was performed to the left atrium, separate from
      each other, by extracardiac approach. The patient had no hemodynamic problems in
      the postoperative period and showed no pulmonary venous obstruction in a control
      angiography performed after 9 months. He has not needed medication and has shown
      no limitation of activity during a follow-up of 5 years.

PMID- 9273969
TI  - Delayed presentation of false abdominal aortic aneurysm following umbilical
      artery catheterisation.
AB  - An eight-month-old male child presented with a nonpulsatile abdominal mass, which
      was detected during a routine follow-up examination. After ultrasound examination
      a tentative diagnosis of pseudoaneurysm of the abdominal aorta was made. An
      umbilical artery catheterisation had been performed for procuring arterial blood
      gases after birth for treatment of birth hypoxia. There was a history of fever
      subsequent to the umbilical artery catheterisation with positive blood and
      catheter tip cultures for coagulase-positive Staphylococci and Klebsiella
      pneumoniae. He had also suffered from infectious arthritis of the left hip joint
      one month after the catheterisation. CT scan with enhancement and angiography
      confirmed the diagnosis. He was treated successfully with excision of the
      aneurysm and direct repair of the aorta. A false abdominal artery aneurysm has
      been noted very rarely as a complication of umbilical artery catheterisation.
      Such an aneurysm most probably develops from infected thrombi which weaken the
      aortic wall. Diagnosis may be delayed as the child can remain asymptomatic. CT
      scan with contrast enhancement can give precise diagnosis. Angiography may be
      done preoperatively. The safest management is early surgery with direct repair.

PMID- 9273970
TI  - Diagnostic significance of mitochondria in four types of renal epithelial
      neoplasms: an ultrastructural study of 60 tumors.
AB  - Mitochondrial morphology was studied in 60 renal epithelial neoplasms, including
      clear cell, papillary, chromophobe cell, and oncocytomas, to see if there are
      significant differences among the various subtypes. Mitochondria from the nephron
      tubular system obtained from 36 patients with glomerular diseases served as
      controls. Significant differences were found in mitochondrial ultrastructure in
      each of the subtypes of renal epithelial tumors. Novel observations were the
      presence of tubulovesicular cristae in many of the mitochondria found in
      chromophobe cell renal carcinomas and the discovery of a possible new oncocytic
      variant of this entity with mitochondria with pseudotubulovesicular and lamellar
      cristae similar to those of renal oncocytomas. This latter finding may be of
      prognostic significance, since renal oncocytomas are benign, while chromophobe
      cell neoplasms may behave in a malignant fashion.

PMID- 9273971
TI  - Gastrointestinal autonomic nerve tumor: a common type of gastrointestinal stromal
      neoplasm.
AB  - Seven of 15 gastrointestinal stromal tumors from the author's file were
      classified as plexosarcomas when examined by electron microscopy and
      immunohistochemistry. Electron microscopy was essential for the diagnosis.

PMID- 9273972
TI  - Immunoelectron microscopical characterization of the epithelioid type of smooth
      muscle cells in human glomus organs.
AB  - The wall structure of arterio-venous anastomoses in human glomus organs was
      studied by immunohistochemistry and immunoelectron microscopy. Smooth muscle
      cells of the epithelioid type I and of the dense type II could be found in the
      media. The immunohistochemical study confirmed the immunopositivity of both
      smooth muscle cell types for alpha-smooth muscle actin, vimentin, and smooth
      muscle myosin. All smooth muscle cells also stained positively for caveolin, a
      recently described structural protein of microvesicles present in selected
      epithelial and nonepithelial cells. The immunoreactivity for cathepsin D,
      however, was much higher in the type I cells than in the type II cells.
      Immunoelectron microscopy revealed that type I cells contain loose arrays of
      alpha smooth muscle actin positive microfilaments, sometimes arranged in small
      bundles, whereas the dense medial smooth muscle cells of the type II have tightly
      packed actin filaments. Only type I cells contained cathepsin D positive
      lysosomes. The data suggest that two types of phenotypic variants of vascular
      smooth muscle cells in the human arterio-venous anastomosis exist: a more
      "synthetic" type I cell and a more contractile type II cell.

PMID- 9273974
TI  - Solid and papillary tumor of the pancreas: ultrastructural observations on two
      contrasting cases.
AB  - Two papillary and solid tumors of the pancreas are reported which differed in
      their clinical features, ultrastructure, and biologic behavior. Both tumors
      contained papillary and solid areas by light microscopy. One tumor followed the
      more usual indolent course. The second patient presented with a liver metastasis
      and died of progressive disease in a relatively short period of time. Neither
      neoplasm showed convincing immunohistochemical or ultrastructural evidence of
      endocrine differentiation, but the electron microscopic findings hinted that this
      tumor possesses at least latent endocrine properties.

PMID- 9273975
TI  - Detection of apoptosis in peripheral blood cells of 31 subjects affected by Down
      syndrome before and after zinc therapy.
AB  - Thirty-one patients affected by Down syndrome (DS) were investigated to study the
      presence of apoptosis in peripheral blood cells in relation to the plasma levels
      of zinc. Twelve patients had undergone therapy with ZnSO4, while the remaining 19
      were untreated. The presence of programmed cell death was evaluated by means of
      electron microscopy, in situ nick translation (NT), and agarose gel
      electrophoresis of DNA. These approaches evidenced the presence of apoptosis in
      peripheral blood cells of patients before therapy with ZnSO4, while after zinc
      supplementation there was a reduction in the number of apoptotic cells. These
      results suggest that the process of programmed cell death in peripheral blood
      cells of patients with Down syndrome is related to the plasma levels of zinc ion.

PMID- 9273976
TI  - Use of electron microscopy and other special techniques in the investigation of
      suspected specimen contamination.
AB  - Contamination of a biopsy or surgical specimen with spurious tissue is an
      uncommon but potentially disastrous event. In this regard, the case of a 5-year
      old boy referred for treatment of an abdominal tumor is presented. Sections made
      from paraffin blocks brought by the family showed both neuroblastoma and a
      spindle cell sarcoma, initially suggesting the possibility of divergent or mixed
      differentiation. However, the resemblance of the spindle cell component to well
      differentiated leiomyosarcoma rather than rhabdomyosarcoma raised the suspicion
      that a specimen contamination had occurred. Electron microscopy was instrumental
      in confirming the smooth muscle nature of the sarcomatous component, leading to a
      fluorescence in situ hybridization study, which established that this component
      was incompatible with the patient's gender. This case illustrates that even when
      the light microscopic differential has been compromised by specimen mishandling,
      electron microscopy can at times provide useful information regarding specimen
      identity, as well as assist in sorting out the correct diagnosis.

PMID- 9273973
TI  - Atypical carcinoid tumor of the larynx: an immunohistochemical, ultrastructural,
      and flow cytometric analysis.
AB  - The clinicopathologic features, including a detailed immunohistochemical,
      ultrastructural, and flow cytometric analysis, are described in three cases of
      atypical carcinoid tumor of the larynx. All patients had metastatic disease
      within cervical lymph nodes at presentation and eventually developed distant
      metastases. Special stains revealed focal intracytoplasmic mucin accumulation,
      and immunohistochemistry showed the tumors to be positive for CAM 5.2, CEA,
      chromogranin A, and calcitonin. In two cases, double-staining techniques revealed
      occasional cells that stained for both mucin and chromogranin A. The
      histochemical and immunohistochemical findings in these two cases were confirmed
      at the ultrastructural level, with most tumor cells containing many
      neurosecretory granules. Smaller numbers of cells contained mucin vacuoles and,
      in occasional cells, both mucin and neuroendocrine granules were identified. The
      three tumors exhibited positive staining with D07 (anti-p53), and flow cytometric
      analysis revealed DNA aneuploidy and polyploidy. The double-staining and
      ultrastructural features indicate that laryngeal atypical carcinoid qualifies for
      the designation of true amphicrine carcinoma. Further study is necessary to
      determine whether mutation of the p53 gene is important in the evolution of
      laryngeal neuroendocrine tumors and whether DNA aneuploidy or polyploidy
      identifies a subset of these tumors with a poor prognosis.

PMID- 9273977
TI  - Ultrastructural localization of insulin-like growth factor-2 (IGF-2) to the
      secretory granules of insulin cells: a study in normal and diabetic (GK) rats.
AB  - By using biochemical and light-microscopical techniques, insulin-like growth
      factor-2 (IGF-2) has recently been found in adult pancreas, co-localized
      immunohistochemically with insulin in the islet B-cells. The purpose of this
      study was to trace IGF-2 immunoreactivity (IR) at the ultrastructural level in
      normal and diabetic Goto-Kakizaki (GK) rats. Using a pre-embedding technique and
      immuno-gold-silver staining, IGF-2 antibody binding was localized exclusively to
      the halo of a subset of secretory beta-granules in normal rats. Insulin IR
      occurred more frequently in the granules. GK rats had, in addition to normal
      looking islets, some islets with irregular shape and an increased amount of
      fibrous tissue, so-called "starfish-shaped" islets. In these, beta-granules were
      usually found, but most of the B-cells were also occupied by large, usually
      electron-translucent vesicles, some resembling crinophagic bodies, i.e., the sign
      of intracellular degradation of secretory granules. In starfish-shaped islets,
      IGF-2 IR was localized to the halo of beta-granules, as in GK islets with normal
      appearance. Occasionally, IGF-2 IR was also found in the cytoplasm and even in
      adjacent fibroblasts. Insulin IR was restricted to beta-granules. Because the
      lysosomes have IGF-2 receptors, the presence of IGF-2 peptide in secretory
      granules could explain why some granules are guided to lysosomes for degradation.

PMID- 9273979
TI  - Case for the panel. Mitochondrial inclusions in prostate adenocarcinoma.

PMID- 9273978
TI  - Small cell undifferentiated carcinoma of the pancreas.
AB  - Small cell undifferentiated carcinoma of the pancreas is a rare neoplasm: Only 12
      cases have previously been documented. This paper describes the clinical
      evolution, immunohistochemical profile, and ultrastructural features of a case
      occurring in a 37-year-old woman.

PMID- 9273980
TI  - Use of a screening instrument in women's health care: detecting relationships
      among victimization history, psychological distress, and medical complaints.
AB  - The interactive relationship between psychological distress and physical health
      is a particularly salient one for women. Routine screening for abuse history and
      current psychological disturbance is essential in providing comprehensive patient
      care. The present study examines the utility of a brief screening measure in
      detecting psychological factors in female patients at a primary care facility.
      Sixty-nine percent of 108 women screened at a women's health clinic reported a
      history of trauma and almost half (49%) reported having been sexually harassed.
      Women presenting to treatment for gynecological problems were more likely to be
      victims of sexual assault and were more likely to report a history of childhood
      sexual abuse. In addition, women seeking specialized health care also reported
      increased rates of stress. Relationships among victimization histories, substance
      use, and eating disturbances were also found. These data suggest the importance
      of assessing psychological disturbances and trauma histories as part of a
      comprehensive medical evaluation.

PMID- 9273981
TI  - Women's disclosure of HIV status: experiences of mistreatment and violence in an
      urban setting.
AB  - Women represent an increasing proportion of AIDS cases and anecdotal reports
      suggest some face substantial risks when others learn they are HIV-positive. The
      purpose of this paper is to describe women's fears and experiences regarding
      disclosure of their HIV status. Fifty HIV-positive women, ages 16-45 from urban
      teaching hospital outpatient clinics, were interviewed using an in-depth,
      qualitative interview. Eighty-six percent of the women were African American and
      56% were current or former IVDU. At the time of the interview, 88% of the women
      had known their HIV status for a year or more. All but one woman had disclosed
      her HIV status to at least one person and 82% had disclosed to multiple people.
      Although two-thirds of the women had been afraid to disclose to others because of
      concerns about rejection, discrimination or violence, three-quarters of the
      sample reported only supportive and understanding responses to their disclosure.
      One-quarter of the sample reported negative consequences of disclosure, including
      rejection, abandonment, verbal abuse and physical assault. Disclosure-related
      violence was discussed by nine women (18%): two who feared violence were relieved
      to find a supportive response; four chose not to disclose their status because
      they feared violence; and three women were verbally or physically assaulted. Fear
      of mistreatment figured prominently in decisions about disclosure among this
      sample. That many women found supportive and understanding responses is
      encouraging. However, there were sufficient examples of negative consequences,
      including violence, to suggest individualized approaches to post-test counseling,
      enhanced support services for HIV-positive women, and public education to
      destigmatize HIV-disease.

PMID- 9273982
TI  - Physical symptoms, somatization, and dissociation in women survivors of childhood
      sexual assault.
AB  - This study investigated the relation between history of sexual abuse,
      somatization, and dissociation in 53 women with a self-reported history of sexual
      assault in childhood and in 30 women who did not report such a history.
      Dissociation and reporting of chronic physical symptoms were positively
      correlated in subjects who had a history of sexual abuse, but this relation did
      not occur in subjects who reported no history of sexual abuse. The more
      perpetrators a subject reported, the greater the number of reported chronic
      physical symptoms. As the age of onset of abuse neared puberty, the more the
      subjects reported childbirth complications. The relation between somatization and
      dissociation is discussed.

PMID- 9273983
TI  - Women and injuries--factors influencing recovery.
AB  - This study focuses on female patients of working age, hospitalized due to
      moderate, mostly orthopaedic injuries. The aim was to highlight the medical and
      non-medical factors affecting outcome. Two groups of women, those who 12 months
      after the injury reported disability within at least three out of five possible
      areas (work, family, household, social life and leisure-time; n = 34), were
      compared with women reporting disability within two areas or less (n = 59). Four
      factors were predictive of outcome according to the multivariate analysis: injury
      severity as measured by the Abbreviated Injury Scale (AIS), self-perceived injury
      related mental and physical health measured by the Visual Analogue Scale (VAS)
      during hospitalization and a history of three or more previous injuries requiring
      medical care. Sociodemographic background factors did not affect the outcome. By
      integrating information from AIS and VAS with the number of previous injuries,
      three quarters of the women were correctly classified; i.e., it was possible to
      detect a majority of those reporting a poorer outcome one year after the injury
      already during hospitalization. Simple screening instruments like these seem to
      be useful in the early detection of vulnerable patients. This study further
      suggests that more attention should be paid to non-medical factors, the
      importance of which may have been underestimated regarding a poorer outcome among
      female patients hospitalized due to injuries. Thus, psychosocial support should
      not only be offered to patients with major trauma or an obvious psychiatric
      disorder, but to all injured patients and should be considered as an integral
      part of medical care.

PMID- 9273984
TI  - Gender differences in participation and responsiveness to a health intervention
      for older Americans.
AB  - Women increasingly outnumber men in the US population (Arber & Ginn, 1993), but
      most research has been conducted with men (Stacey & Olesen, 1988). The purpose of
      this study was to determine whether older men and women differ in their
      participation rates and in their responsiveness to a health intervention. Three
      hundred sixty-three health maintenance organization members with osteoarthritis,
      60 years of age or older, were randomly assigned to a control group or to receive
      social support, education, or a combination of education and social support,
      education, or a combination of education and social support. Of the 363 randomly
      assigned members, 245 completed all of the follow-up assessments. Men and women
      volunteered in proportion to their representation in the osteoarthritis
      population. Although the genders differed in several ways, the interventions were
      equally effective for men and women, and the study results applied to both
      genders.

PMID- 9273985
TI  - Cystic fibrosis and calcium oxalate nephrolithiasis.
AB  - During the past six years, we have treated eight patients with cystic fibrosis
      (CF) for nephrolithiasis. In seven patients, the stones were comprised of calcium
      oxalate. Another six patients had calcium oxalate crystalluria. In our CF
      population of 140 patients, this represents a cumulative incidence of calcium
      oxalate nephrolithiasis of 5.7 percent and an additional 4.2 percent incidence of
      crystalluria. Experience with these patients is reviewed. Pancreatic
      insufficiency was universally associated with nephrolithiasis or crystalluria.
      Diabetes and cirrhosis were also common. Predisposing factors and potential
      mechanisms of stone disease in pancreatic insufficient CF patients are discussed,
      focusing on the relationship between fat malabsorption in CF to oxalate
      metabolism.

PMID- 9273986
TI  - Cytomegalovirus infection masquerading as an ulcerative colitis flare-up: case
      report and review of the literature.
AB  - We report the case of a patient with a case of cytomegalovirus (CMV) colitis,
      which presented as a flare-up of her ulcerative colitis. Standard treatment for
      the flare-up, which included intravenous corticosteroids, bowel rest, topical
      salicylates and ultimately colectomy were not effective. The patient did not
      improve until therapy with intravenous ganciclovir was initiated. There have been
      26 previous reports of CMV colitis complicating inflammatory bowel disease (IBD).
      The diagnosis is not frequently entertained and, if not made, leads to a high
      rate of colectomy (67 percent) and mortality (33 percent). Appropriate antiviral
      therapy appears to eliminate these complications, thus a high index of suspicion
      for CMV superinfection in cases of IBD refractory to traditional therapy is
      warranted.

PMID- 9273987
TI  - Intestinal "bioavailability" of solutes and water: we know how but not why.
AB  - Only minimal quantities of ingested and normally secreted solutes and water are
      excreted in the stool. This near 100% bioavailability means that the diet and
      kidneys are relatively more important determinants of solute, water and acid-base
      balance than the intestine. Intestinal bioavailability is based on excess
      transport capacity under normal conditions and the ability to adapt to altered or
      abnormal conditions. Indeed, the regulatory system of the intestine is as
      complex, segmented and multi factorial as in the kidney. Alterations in the rate
      and intestinal site of absorption reflect this regulation, and the diagnosis and
      treatment of various clinical abnormalities depend on the integrity of intestinal
      absorptive processes. However, the basis for this regulation an bioavailability
      are uncertain. Perhaps they had survival value for mammals, a phylogenic class
      that faced the twin threats of intestinal pathogens and shortages of solutes and
      water.

PMID- 9273988
TI  - Clinical neurosciences in the decade of the brain: hypotheses in neuro-oncology.
      VEG/PF acts upon the actin cytoskeleton and is inhibited by dexamethasone:
      relevance to tumor angiogenesis and vasogenic edema.
AB  - HYPOTHESIS: We have proposed that VEG/PF acts by transforming the cytoskeletal
      architecture of microvascular endothelial cells. BACKGROUND: Evidence supporting
      a pivotal role for vascular endothelial growth/permeability factor (VEG/PF) in
      tumor angiogenesis and edemagenesis is compelling. VEG/PF exhibits specific
      endothelial cell mitogenicity and is expressed by brain tumors exhibiting
      increased vascularity and microvascular extravasation. The mechanistic cascade
      that follows VEG/PF-tyrosine kinase receptor binding remains uncertain, however.
      Actin is a cytoskeletal protein that regulates cellular motility, shape and
      vesicular transport. Regulation of actin stress fibers, cell-surface focal
      adhesions and plasmalemmal "ruffles" is mediated by tyrosine kinase activation of
      GTP-binding proteins that are in turn linked to intracellular calcium flux. As
      VEG/PF is known to induce cytosolic calcium ion transients in endothelial cells,
      actin microfilaments would appear to be logical candidates for study of a
      cytocontractile response mediated by calcium signal transduction. METHODS: VEG/PF
      induced endothelial actin cytoskeletal changes were studied using rhodamine
      phalloidin staining and fluorescence photomicrography. RESULTS: When exposed to
      VEG/PF, cultured endothelial cells from human umbilical veins and rat brain
      microvessels exhibited a reversible, dose-related reorganization of actin stress
      fibers, cell contraction and rounding, and widening of the intercellular spaces.
      VEG/PF perturbation also induced plasmalemmal "ruffling". All VEG/PF-induced
      cytoskeletal changes were inhibited by preincubating endothelial cells with
      dexamethasone or anti-VEG/PF IgG antibody. CONCLUSION: The findings support a
      role for VEG/PF-induced cytoskeletal alterations in the pathophysiology of brain
      tumor angiogenesis and edemagenesis. These observations are likely to be directly
      linked to VEG/PF-induced endothelial cytosolic calcium flux. Insight into the
      mechanism of dexamethasone's clinical efficacy is also provided.

PMID- 9273989
TI  - Development of duodenal ulcer concomitant with successful Helicobacter pylori
      eradication.
AB  - The discovery of an association of the bacterium Helicobacter pylori and
      gastroduodenal ulcer disease has changed our thinking about the pathogenesis of
      peptic ulcers. The focus of treatment has been directed away from acid
      suppression as the only therapeutical component to the additional use of
      antibiotics for eradication of this microorganism. We present the case of a woman
      with chronic peptic ulcer disease in whom the development of a duodenal ulcer was
      documented concomitant with Helicobacter pylori eradication therapy utilizing
      omeprazole and amoxycillin. This regimen had been successful in both healing
      another peptic lesion in the duodenal bulb and eradicating Helicobacter pylori,
      yet it proved unable to prevent the early rise of a new ulcer. In conclusion,
      this finding suggests that Helicobacter pylori and hypersecretory states are not
      the only causes of relapsing duodenal ulceration.

PMID- 9273990
TI  - Coombs-negative severe hemolysis associated with hepatitis A.
AB  - Mild anemia can occasionally be observed during viral hepatitis, but severe
      hemolysis has previously only been reported in a few patients with glucose-6
      phosphate dehydrogenase (G6PD) deficiency. We report a case of massive acute
      hemolysis associated with an acute hepatitis A in a 39-year-old woman in the
      absence of G6PD-deficiency. The patient was also suffering from mild rheumatoid
      arthritis. All known factors responsible for hemolysis were ruled out. Although
      tests for autoimmune hemolytic anemia were negative the patient made a dramatic
      recovery after treatment with corticosteroids, suggesting an immune mediated
      mechanism nonetheless.

PMID- 9273991
TI  - Cyclophosphamide as alternative immunosuppressive therapy for autoimmune
      hepatitis--report of three cases.
AB  - Autoimmune hepatitis is a chronic inflammatory disorder of the liver with a
      fluctuating course, which often requires long-term immunosuppressive therapy in
      order to prevent fibrosis to the liver. The mainstay of immunosuppressive therapy
      is the use of corticosteroids, usually in conjunction with azathioprine. However,
      in a subgroup of patients with severe side effects or intolerance of standard
      therapy there is a need for alternative immunosuppressive agents. We describe the
      successful long-term treatment of three patients with severe autoimmune hepatitis
      with an immunosuppressive regimen consisting of cyclophosphamide and
      corticosteroids. In the reported patients we were able to induce remission with
      cyclophosphamide in a dose of 1-1.5 mg/kg bodyweight in combination with a
      tapering dose of corticosteroids beginning with 1 mg/kg bodyweight. After
      induction we were able to maintain histology proven remission with low doses of
      corticosteroids (2.5-10 mg/day) together with 50 mg of cyclophosphamide every
      other day. With this dose of cyclophosphamide we have neither observed relapse of
      autoimmune hepatitis nor severe side effects in a cumulative observation period
      of more than twelve years in the three patients. As a consequence of our
      favourable experience with cyclophosphamide in the reported cases, we propose
      cyclophosphamide as an alternative to azathioprine in cases of autoimmune
      hepatitis with severe side effects of intolerance of standard therapy.

PMID- 9273992
TI  - Clinical perspectives of a sonographic secretin test.
AB  - The normal-sized pancreatic duct can be demonstrated today by sonography in about
      90% of all persons examined. In healthy individuals intravenous bolus injection
      of secretin generally leads to a short-lasting distinct dilatation of Wirsung's
      duct being likewise visible on ultrasonography. Further investigations showed no
      or only a slight secretin-induced pancreatic duct dilatation in chronic
      pancreatitis, whereas patients with papillary or pancreatic duct stenosis had a
      marked and prolonged duct enlargement after stimulation. Different authors
      reported a high sensitivity and specificity of this sonographic secretin test in
      the diagnosis of chronic pancreatitis, even in early stages. In patients with
      pancreas divisum the secretin test result seems to be less uniform, a marked and
      prolonged duct enlargement after secretin stimulation, however, has been
      successfully used as a diagnostic criterion of accessory sphincter obstruction.
      Recently this test method has also been used to differentiate the etiology of
      cystic pancreatic lesions under observation by endoscopic ultrasonography. Since
      sonographic measurement of the pancreatic duct diameter before and after secretin
      stimulation is easy to perform with modern technical equipment, it could be a
      useful screening test for different diagnostic questions in pancreatic disease.
      Further investigations are needed for the evaluation of its reliability and
      standardization.

PMID- 9273993
TI  - The role of entropy in the discrimination between CO and O2 in myoglobin.
AB  - Using stopped-flow rapid mixing and flash photolysis techniques, the dissociation
      rate coefficients of horse carbonmonoxy myoglobin (hMbCO) and oxygenated
      myoglobin (hMbO2) in aqueous solution have been determined as a function of
      temperature between 274 and 342 K. From the Arrhenius plot, an activation
      enthalpy for dissociation of 74 kJ/mol was obtained for both ligands. The
      pronounced kinetic differences arise from markedly different pre-exponentials. We
      compare the Arrhenius parameters with those of the association reaction, as
      measured at cryogenic temperatures. In our analysis we conclude that the entropy
      loss upon binding of O2 is twice as large as that for CO. Taking reasonable
      estimates for the frequency factor, the transition state entropy in hMbO2 is
      located roughly half way in between the entropies of the bound and unbound
      states. By contrast, the entropy of the transition state in hMbCO appears to be
      identical to that of the bound state. Possible structural reasons for the
      different behavior are discussed.

PMID- 9273994
TI  - Conductometric properties of human erythrocyte membranes: dependence on
      haematocrit and alkali metal ions of the suspending medium.
AB  - The electrical properties of the cytoplasmatic membrane of human erythrocyte
      cells have been evaluated by means of dielectric spectroscopy measurements in the
      radiowave frequency range, using the so-called "suspension method". Measurements
      have been carried out at different volume fractions of the corpuscular phase (the
      cell haematocrit) in order to investigate the influence of the cell-cell
      interactions on the electrical parameters (the membrane permittivity epsilon and
      the membrane conductivity sigma) of the cell membrane and a set of new values are
      proposed. Moreover, the influence of different alkali metal ions (Na+, K+, Cs+,
      Li+) on the ion permeation properties of the membrane are investigated and the
      structural alterations in the membrane organized briefly discussed.

PMID- 9273996
TI  - Diheterocyclanes as synthons for the preparation of novel series of nucleoside
      and acyclonucleoside analogues.
AB  - Convenient synthesis of 1-[[3-(2-hydroxyethylhetero)-1-alkoxy]alkyl]-5
      fluorouracils 3-8 was accomplished via the use of tin (IV) chloride, capable of a
      1,4-chelation on alkoxy-1,4-diheteroepanes. Increasing the reaction time led to 5
      FU seven-membered nucleoside analogues which could be considered as upper
      isosteres of the effective antitumour agent Ftorafur. Using 1-[[3-(2
      hydroxyethoxy)-1-alkoxy]propyl]-5-fluorouracil as a parent drug, several chemical
      modifications on the acyclic moiety were made with the aim of obtaining new
      compounds showing significant antiproliferative activity in rhabdomyosarcoma (RD)
      cells. 14 treatment in vitro caused time- and dose-dependent growth inhibition on
      RD cells. Interestingly, when they were treated with doses of 35 microM and 140
      microM of 14 for 6 days, they showed morphological and phetotypic differentiation
      with increased expression of desmin, alpha-actinin and tropomyosin. We suggest a
      potential role for differentiation therapy as a therapeutic approach to the
      treatment of rhabdomyosarcoma.

PMID- 9273995
TI  - Quartz crystal microbalance investigation of the interaction of bacterial toxins
      with ganglioside containing solid supported membranes.
AB  - The binding of cholera toxin, tetanus toxin and pertussis toxin to ganglioside
      containing solid supported membranes has been investigated by quartz crystal
      microbalance measurements. The bilayers were prepared by fusion of phospholipid
      vesicles on a hydrophobic monolayer of octanethiol chemisorbed on one gold
      electrode placed on the 5 MHz AT-cut quartz crystal. The ability of the
      gangliosides GM1, GM3, GD1a, GD1b, GT1b and asialo-GM1 to act as suitable
      receptors for the different toxins was tested by measuring the changes of quartz
      resonance frequencies. To obtain the binding constants of each ligand-receptor
      couple Langmuir-isotherms were successfully fitted to the experimental adsorption
      isotherms. Cholera toxin shows a high affinity for GM1 (Ka = 1.8.10(8)M-1), a
      lower one for asialo-GM1 (Ka = 1.0.10(7)M-1) and no affinity for GM3. The C
      fragment of tetanus toxin binds to ganglioside GD1a, GD1b and GT1b containing
      membranes with similar affinity (Ka approximately 10(6)M-1), while no binding was
      observed with GM3. Pertussis toxin binds to membranes containing the ganglioside
      GD1a with a binding constant of Ka = 1.6.10(6)M-1, but only if large amounts (40
      mol%) of GD1a are present. The maximum frequency shift caused by the protein
      adsorption depends strongly on the molecular structure of the receptor. This is
      clearly demonstrated by an observed maximum frequency decrease of 99 Hz for the
      adsorption of the C-fragment of tetanus toxin to GD1b. In contrast to this large
      frequency decrease, which was unexpectedly high with respect to Sauerbrey's
      equation, implying pure mass loading, a maximum shift of only 28 Hz was detected
      after adsorption of the C-fragment of tetanus toxin to GD1a.

PMID- 9273997
TI  - Novel bioreductive anticancer agents based on indolequinones.
AB  - The background to bioreductive drugs based on indolequinones is surveyed, and the
      development of novel cyclopropamitosenes as potent anticancer agents is reviewed.
      Thiazolylindoles were also investigated as potential inhibitors of topoisomerase
      II.

PMID- 9273998
TI  - Acyclic glycosidopyrroles analogues of ganciclovir: synthesis and biological
      activity.
AB  - Acyclic glycosidopyrroles of type 3 were synthetized in good overall yields,
      according to the Scheme. When evaluated for antiviral activity against DNA and
      RNA viruses, only compound in which R1 = R2 = Ph, R3 = NH2 was found to inhibit
      the HIV-1 replication at concentrations that were not cytotoxic for MT-4 cells.

PMID- 9273999
TI  - Heterocyclic structures useful in medicinal chemistry: the case of pyrazino[2,3
      c][1,2,6]thiadiazine 2,2-dioxide.
AB  - Different aspects of a particular kind of heterocycle, namely pyrazino[2,3
      c][1,2,6]thiadiazine 2,2-dioxide are discussed. These include synthesis,
      reactivity, tautomerism and acid-base properties, results of x-ray analysis and
      molecular orbital calcultations. Besides, some of the derivatives have shown
      interesting biological effects, among which are the diuretic properties which are
      also presented.

PMID- 9274000
TI  - Ligands of the histamine H3-receptor: new potent antagonists of the 2
      thioimidazole type.
AB  - An overview of H3-receptor ligands is presented, with particular attention to
      antagonists. The protein binding of the classical H3-receptor antagonist
      thioperamide and its effect on in vivo distribution are discussed. A series of H3
      receptor antagonists characterised by the presence of an imidazole ring, a spacer
      (ethylthio-, ethylamino-, propylthio- or propylamino-chain), a second heterocycle
      nucleus and a lipophilic group is described. Their H3-receptor antagonist potency
      has been measured on electrically stimulated guinea-pig intestine, and their
      affinity for central H3-receptor has been determined by competitive inhibition of
      [3H]N alpha-methylhistamine binding to rat cortex. Biphasic inhibition curves
      have been observed in some cases. Compounds endowed with interesting activity
      belong mostly to the class of 2-[[2-[4(5)-imidazolyl]ethyl]thio]imidazole, having
      a phenyl or a cyclohexyl group.

PMID- 9274001
TI  - Chemoenzymatic synthesis of chiral biologically active heterocycles.
AB  - The chemoenzymatic approach to the preparation of some chiral biologically active
      heterocycles is discussed. Synthetic strategies took advantage of
      enantioselective bioconversion processes carried out on suitable reaction
      intermediates. Reductions of carbonyl compounds catalyzed by different alcohol
      dehydogenases (TBADH from Thermoanaerobium brockii, 20 beta-HSDH from
      Streptomyces hydrogenans, beta-HSDH from Pseudomonas testosteroni) allowed the
      preparation with high enantiomeric purity of the eutomer of broxaterol (a
      selective beta 2-adrenergic agonist) and six out of the eight muscarine
      stereoisomers. On the other hand, hydrolyses, catalyzed by lipase PS (from
      Pseudomonas cepacia), of racemic butyrates were the key step in the synthesis of
      both the enantiomers of two muscarinic antagonists. Finally, the preparation of
      acetyl cycloserine antipodes was attained by means of a highly enantioselective
      hydrolysis catalyzed by lipase from Chromobacterium viscosum.

PMID- 9274002
TI  - Semisynthetic glycopeptides: chemistry, structure-activity relationships and
      prospects.
AB  - Glycopeptides are a class of naturally occurring antibiotics produced by
      fermentation of microorganisms. They inhibit cell wall biosynthesis in bacteria
      by forming a complex with the C-terminal D-alanyl-D-alanine of growing
      peptidoglycan chains. Glycopeptides are active against Gram-positive bacteria
      including the major pathogens. Among all the glycopeptides that have been
      discovered, only vancomycin and teicoplanin are on the market for the clinical
      use. By modification of the natural glycopeptide it is possible to increase its
      activity against methicillin-resistant Staphylococcus aureus and coagulase
      negative staphylococci. Basic amides of teicoplanin aglycon have produced one
      compound endowed with interesting activity against Gram-negative bacteria because
      of its ability to cross the outer membrane of this last bacteria. Selective
      degradation of teicoplanin has given a tetrapeptide, a key intermediate that has
      been used as starting material for the synthesis of new non natural
      glycopeptides. One of them has shown a weak but promising activity against Van A
      Enterococci highly resistant to natural glycopeptides.

PMID- 9274003
TI  - Sulfone derivatives with anti-HIV activity.
AB  - Following the discovery of anti-HIV properties of suramin great efforts were
      devoted to design novel NNRT agents with the aims to find novel drugs for the
      clinical therapeutic management of AIDS. Sulfone and sulfonamide derivatives were
      studied by NCI at Bethesda as potential anti-HIV-1 agents and nitrophenyl phenyl
      sulfone (NPPS) was selected as lead compound for further investigations. At the
      same time Merck Laboratories discovered L-737,126, a potent indolyl aryl sulfone
      with inhibitory activity against reverse transcriptase. These studies stimulated
      novel search in the sulfone series and both diarylsulfones and cyclic sulfone
      derivatives were investigated. Our decennial interest in chemotherapeutic agents
      containing a pyrrole ring pulsed us to synthesize and test as anti-HIV-1 agents a
      number of pyrryl aryl sulfones (PASs), pyrrolobenzothiadiazepine (PBTDs) and
      pyrrolobenzothiazepine related sulfones. The new sulfone derivatives inhibit
      selectively HIV-1 and were inactive against HIV-2. Most of them were as active
      as, if not more active than, nevirapine.

PMID- 9274004
TI  - Oxazolidinones, dihydrofuranones, and pyrrolidinones as inactivators and
      substrates of monoamine oxidase B: approaches to the design of antiparkinsonian
      agents.

PMID- 9274005
TI  - Is the ribulose monophosphate pathway widely distributed in bacteria?

PMID- 9274006
TI  - Cadmium-specific formation of metal sulfide 'Q-particles' by Klebsiella
      pneumoniae.
AB  - Klebsiella pneumoniae overcomes cadmium toxicity through the 'biotrans-formation'
      of cadmium ions into photoactive, nanometre-sized CdS particles deposited on the
      cell surface. The kinetics of particle formation during batch culture growth was
      monitored by electron microscopy (EM), energy-dispersive X-ray analysis and
      electronic absorption spectroscopy (EAS). During the deceleration phase of
      bacterial growth, the presence of CdS particles on the outer cell wall of K.
      pneumoniae (> or = 5 nm in diameter) was detected by EM. The size of these
      electron-dense particles continued to increase throughout the stationary phase of
      growth, with some of the particles reaching a diameter > 200 nm. The formation of
      the extracellular CdS particles contributed to around 3-4% of the total cell
      biomass. EAS undertaken on these extracellular 'bio-CdS' particles suggested that
      the large 'superparticles' observed by EM, e.g. 200 nm, were aggregates of
      smaller particles termed 'Q-particles', approximately 4 nm in diameter. Metal
      sulfide particles were not formed in batch cultures of K. pneumoniae grown in the
      presence of lead, zinc, mercury, copper or silver ions. Growth in the presence of
      lead ions resulted in the formation of extracellular electron-dense particles
      containing lead but not sulfide or phosphate. Intracellular phosphorus-containing
      electron-opaque particles were formed during growth in the presence of copper and
      mercury. Intracellular electron-dense particles were formed in the presence of
      zinc ions but these did not contain phosphorus. From these results it was thought
      that metal sulfide formation in K. pneumoniae showed some cadmium-specificity.
      When cadmium and zinc ions were both added to the growth medium, metal sulfide
      particles were formed that were predominantly composed of cadmium, e.g. 48.6%
      cadmium and 0.04% zinc. Similarly, when cadmium and lead ions were both present
      during growth only CdS particles formed. In both cases analysis of the cells by
      EAS confirmed the presence of CdS only. These observations suggest that the
      mechanism of CdS formation is unlikely to occur simply through a cadmium-induced
      release of hydrogen sulfide by the cells into the external environment. If
      hydrogen sulfide production was the mechanism of sulfide formation then metal
      sulfide particles containing lead and zinc ions in addition to cadmium ions
      should have been produced.

PMID- 9274007
TI  - Diversity and differential distribution of IS231, IS232 and IS240 among Bacillus
      cereus, Bacillus thuringiensis and Bacillus mycoides.
AB  - Bacillus cereus, Bacillus thuringiensis and Bacillus mycoides are very closely
      related bacteria, generally considered as subspecies of B. cereus sensu lato.
      Different transposable elements have been isolated from B. thuringiensis,
      including IS231, IS232 and IS240 and their variants. The distribution of these
      three insertion sequences (IS) within the B. cereus group has been investigated
      in 90 strains of B. thuringiensis (representing 61 serovars), in 30 reference
      strains of B. cereus and in 33 strains of B. mycoides. Since these IS elements
      are delimited by well-conserved and specific inverted repeats, the use of primers
      corresponding to these ends allowed their amplification by PCR. The results
      showed that IS231 is the most abundant element in the three taxa, whereas IS232
      is apparently exclusively associated with B. thuringiensis. Hybridization and
      Dral RFLP analysis of the PCR products confirmed and extended knowledge of the
      heterogeneity previously observed among iso-IS231 elements. Moreover, a similar
      diversity was observed among iso-IS240 elements. This contrasted with the
      relative homogeneity displayed by iso-IS232 elements. No specific association
      appeared to exist between any particular iso-element and a specific strain or
      serotype.

PMID- 9274009
TI  - Association of newly discovered IS elements with the dichloromethane utilization
      genes of methylotrophic bacteria.
AB  - Dichloromethane (DCM) dehalogenases enable facultative methylotrophic bacteria to
      utilize DCM as sole carbon and energy source. DCM-degrading aerobic
      methylotrophic bacteria expressing a type A DCM dehalogenase were previously
      shown to share a conserved 4.2 kb BamHI DNA fragment containing the dehalogenase
      structural gene, dcmA, and dcmR, the gene encoding a putative regulatory protein.
      Sequence analysis of a 10 kb DNA fragment including this region led to the
      identification of three types of insertion sequences identified as IS1354, IS1355
      and IS1357, and also two ORFs, orf353 and orf192, of unknown function. Two
      identical copies of element IS1354 flank the conserved 4.2 kb fragment as a
      direct repeat. The occurrence of these newly identified IS elements was shown to
      be limited to DCM-utilizing methylotrophs containing a type A DCM dehalogenase.
      The organization of the corresponding dcm regions in 12 DCM-utilizing strains was
      examined by hybridization analysis using IS-specific probes. Six different groups
      could be defined on the basis of the occurrence, position and copy number of IS
      sequences. All groups shared a conserved 5.6 kb core region with dcmA, dcmR,
      orf353 and orf192 as well as IS1357. One group of strains including Pseudomonas
      sp. DM1 contained two copies of this conserved core region. The high degree of
      sequence conservation observed within the genomic region responsible for DCM
      utilization and the occurrence of clusters of insertion sequences in the vicinity
      of the dcm genes suggest that a transposon is involved in the horizontal transfer
      of the DCM-utilization character among methylotrophic bacteria.

PMID- 9274008
TI  - Tn5041: a chimeric mercury resistance transposon closely related to the toluene
      degradative transposon Tn4651.
AB  - This paper reports the discovery and characterization of Tn5041, a novel-type
      transposon vehicle for dissemination of mercury resistance in natural bacterial
      populations. Tn5041 (14876 bp), identified in a Pseudomonas strain from a mercury
      mine, is a Tn3 family mercury resistance transposon far outside the Tn21
      subgroup. As in other Tn3 family transposons, Tn5041 duplicates 5 bp of the
      target sequence following insertion. Tn5041 apparently acquired its mer operon as
      a single-ended relic of a transposon belonging to the classical mercury
      resistance transposons of the Tn21 subgroup. The putative transposase and the 47
      bp terminal inverted repeats of Tn5041 are closely related to those of the
      toluene degradative transposon Tn4651 and fall into a distinct subgroup on the
      fringe of the Tn3 family. The amino acid sequence of the putative resolvase of
      Tn5041 resembles site-specific recombinases of the integrase family. Besides the
      mer operon and putative transposition genes, Tn5041 contains a 4 kb region that
      accommodates a number of apparently defective genes and mobile elements.

PMID- 9274010
TI  - Adhesion of Pseudomonas aeruginosa to silicone rubber in a parallel plate flow
      chamber in the absence and presence of nutrient broth.
AB  - The physico-chemical cell-surface properties of Pseudomonas aeruginosa AK1 and
      its adhesion to silicone rubber under flow were compared for cells suspended in
      phosphate-buffered saline (PBS) or PBS supplemented with 2% nutrient broth.
      Addition of 2% nutrient broth to cells suspended in PBS yielded minimal growth
      and did not significantly change the mean zeta potential of the organisms, which
      was around -13 mV. However, a comparatively larger proportion of the organisms
      had more negative zeta potentials in the presence of nutrient broth. This change
      was concurrent with a slight decrease in cell-surface hydrophobicity, as measured
      by water contact angles, from 119 degrees to around 112 degrees. The initial
      deposition rate of P. aeruginosa AK1 to silicone rubber, as studied in a parallel
      plate flow chamber, increased from 344 cm-2 s-1 in the absence of nutrient broth
      to 505 cm-2 s-1 in its presence. No stationary level of adhesion was observed in
      the presence of nutrient broth, instead the number of adhering cells increased
      steadily at a rate of approximately 85 cm-2 s-1. Fluorescent staining of adhering
      cells demonstrated that for adhesion from buffer only 2% of the adhering cells
      were metabolically active, whereas in case of deposition from PBS supplemented
      with nutrient broth, 67% of the adhering cells were metabolically active. It is
      concluded that the deposition rates measured in the parallel plate flow chamber
      with 2% nutrient broth added to the PBS suspension represent an interplay of
      adhesion and surface-associated growth.

PMID- 9274011
TI  - Spatial interactions between subsurface bacterial colonies in a model system: a
      territory model describing the inhibition of Listeria monocytogenes by a nisin
      producing lactic acid bacterium.
AB  - The effect of spatial separation on interactions between subsurface bacterial
      colonies was tested using a model system: the inhibition of Listeria
      monocytogenes by nisin-producing and nisin-non-producing Lactococcus lactis
      subsp. lactis. Separation distance was controlled by altering the number of
      inoculum organisms within the agar. Mean separation distance was calculated by
      determining the mean volume available to each cell at the start of the
      experiment. Inhibition was assessed by comparing the growth of L. monocytogenes
      in pure culture with its growth in the presence of Lac. lactis subsp. lactis.
      Increasing the distance between colonies resulted in an exponential decrease in
      inhibition. When L. monocytogenes and Lac. lactis subsp. lactis colonies were
      within 100 microns of each other, the increase in cell numbers per L.
      monocytogenes colony was only 0.6 c.f.u. (which indicated some cells had become
      non-viable). This was a log reduction of 3.5 compared to the pure culture
      control. A separation distance of 1000 microns resulted in a L. monocytogenes
      colony growth increment of 2.5 x 10(2) c.f.u. per colony, a log reduction of 3.0
      compared to the control. Increasing the separation distance to 3000 microns
      resulted in a L. monocytogenes colony growth increment of 1.3 x 10(6) c.f.u. per
      colony, a log reduction of 0.9 compared to the control. The effects of nisin and
      acidity were investigated by using a nisin-non-producing strain of Lac. lactis
      subsp. lactis and by buffering the medium. Data were obtained for the effect of
      separation on inhibition, as well as competition between colonies of the same
      species. The inhibition was mathematically described in terms of a simplified
      'territory' model of immobilized bacterial growth. There was a strong qualitative
      agreement between the mathematical model and the experimental data. It was
      concluded that the phenomenon of propinquity is of important consideration when
      modeling and predicting microbial growth within solid food systems.

PMID- 9274012
TI  - Restoration of wild-type virulence to Tri5 disruption mutants of Gibberella zeae
      via gene reversion and mutant complementation.
AB  - Gibberella zeae is a pathogen of small grain crops and produces trichothecene
      mycotoxins in infected host tissue. The role of trichothecenes in the virulence
      of G. zeae was previously investigated using trichothecene-non-producing mutants
      that were generated via transformation-mediated disruption of a gene (Tri5) that
      encodes the first enzyme in the trichothecene biosynthetic pathway. The mutants
      were less virulent on some hosts than the wild-type strain from which they were
      derived. Here, we used two approaches to determine whether the reduced virulence
      of mutants was due specifically to Tri5 disruption or to non-target effects
      caused by the transformation process. First, we generated a revertant from a Tri5
      disruption mutant by allowing the mutant to pass through the sexual phase of its
      life cycle. In approximately 2% of the resulting progeny the disrupted Tri5 had
      reverted to wild-type; however, only one of three revertant progeny also regained
      the ability to produce trichothecenes. In the second approach, we complemented
      the Tri5 mutation in a disruption mutant by transforming the mutant with a
      plasmid carrying a functional copy of Tri5. In all transformants examined, the
      ability to produce trichothecenes was restored. The restoration of trichothecene
      production in the revertant progeny and in the complemented mutant was
      accompanied by restoration of wild-type or near wild-type levels of virulence on
      wheat seedlings (cultivar Wheaton). The results indicate that the reduced
      virulence of the mutants was caused by disruption of Tri5 rather than non-target
      effects resulting from the transformation process. The results also provide
      further evidence that trichothecenes contribute to the virulence of plant
      pathogenic fungi.

PMID- 9274014
TI  - Three Neocallimastix patriciarum esterases associated with the degradation of
      complex polysaccharides are members of a new family of hydrolases.
AB  - Acetylesterase and cinnamoyl ester hydrolase activities were demonstrated in
      culture supernatant of the anaerobic ruminal fungus Neocallimastix patriciarum. A
      cDNA expression library from N. patriciarum was screened for esterases using beta
      naphthyl acetate and a model cinnamoyl ester compound. cDNA clones representing
      four different esterase genes (bnaA-D) were isolated. None of the enzymes had
      cinnamoyl ester hydrolase activity, but two of the enzymes (BnaA and BnaC) had
      acetylxylan esterase activity, bnaA, bnaB and bnaC encode proteins with several
      distinct domains. Carboxy-terminal repeats in BnaA and BnaC are homologous to
      protein-docking domains in other enzymes from Neocallimastix species and another
      anaerobic fungus, a Piromyces sp. The catalytic domains of BnaB and BnaC are
      members of a recently described family of Ser/His active site hydrolases [Upton,
      C. & Buckley, J.T. (1995). Trends Biochem Sci 20, 178-179]. BnaB exhibits 40%
      amino acid identity to a domain of unknown function in the CelE cellulase from
      Clostridium thermocellum and BnaC exhibits 52% amino acid identity to a domain of
      unknown function in the XynB xylanase from Ruminococcus flavefaciens. BnaA,
      whilst exhibiting less than 10% overall amino acid identity to BnaB or BnaC, or
      to any other known protein, appears to be a member of the same family of
      hydrolases, having the three universally conserved amino acid sequence motifs.
      Several other previously described esterases are also shown to be members of this
      family, including a rhamnogalacturonan acetylesterase from Aspergillus aculeatus.
      However, none of the other previously described enzymes with acetylxylan esterase
      activity are members of this family of hydrolases.

PMID- 9274015
TI  - The KIPHO5 gene encoding a repressible acid phosphatase in the yeast
      Kluyveromyces lactis: cloning, sequencing and transcriptional analysis of the
      gene, and purification and properties of the enzyme.
AB  - A secreted phosphate-repressible acid phosphatase from Kluyveromyces lactis has
      been purified and the N-terminal region and an internal peptide have been
      sequenced. Using synthetic oligodeoxyribonucleotides based on the sequenced
      regions, the genomic sequence, KIPHO5, encoding the protein has been isolated.
      The deduced protein, named KIPho5p, consists of 469 amino acids and has a
      molecular mass of 52520 Da (in agreement with the data obtained after treatment
      of the protein with endoglycosidase H). The purified enzyme shows size
      heterogeneity, with an apparent molecular mass in the range 90-200 kDa due to the
      carbohydrate content (10 putative glycosylation sites were identified in the
      sequence). A 16 amino acid sequence at the N-terminus is similar to previously
      identified signal peptides in other fungal secretory proteins. The putative
      signal peptide is removed during secretion since it is absent in the mature
      secreted acid phosphatase. The gene can be induced 400-600-fold by phosphate
      starvation. Consensus signals corresponding to those described for Saccharomyces
      cerevisiae PHO4- and PHO2-binding sites are found in the 5' region. Northern blot
      analysis of total cellular RNA indicates that the KIPHO5 gene codes for a 1.8 kb
      transcript and that its expression is regulated at the transcriptional level.
      Chromosomal hybridization indicated that the gene is located on chromosome II.
      The KIPHO5 gene of K. lactis is able to functionally complement a pho5 mutation
      of Sacch. cerevisiae. Southern blot experiments, using the KIPHO5 gene as probe,
      show that some K. lactis reference strains lack repressible acid phosphatase,
      revealing a different gene organization for this kind of multigene family of
      proteins as compared to Sacch. cerevisiae.

PMID- 9274016
TI  - The Sch9 protein kinase in the yeast Saccharomyces cerevisiae controls cAPK
      activity and is required for nitrogen activation of the fermentable-growth-medium
      induced (FGM) pathway.
AB  - In cells of the yeast Saccharomyces cerevisiae, trehalase activation, repression
      of CTT1 (catalase), SSA3 (Hsp70) and other STRE-controlled genes, feedback
      inhibition of cAMP synthesis and to some extent induction of ribosomal protein
      genes is controlled by the Ras-adenylate cyclase pathway and by the fermentable
      growth-medium-induced pathway (FGM pathway). When derepressed cells are shifted
      from a non-fermentable carbon source to glucose, the Ras-adenylate cyclase
      pathway is transiently activated while the FGM pathway triggers a more lasting
      activation of the same targets when the cells become glucose-repressed.
      Activation of the FGM pathway is not mediated by cAMP but requires catalytic
      activity of cAMP-dependent protein kinase (cAPK; Tpk1, 2 or 3). This study shows
      that elimination of Sch9, a protein kinase with homology to the catalytic
      subunits of cAPK, affects all target systems in derepressed cells in a way
      consistent with higher activity of cAPK in vivo. In vitro measurements with
      trehalase and kemptide as substrates confirmed that elimination of sch9 enhances
      cAPK activity about two- to threefold, in both the absence and presence of cAMP.
      In vivo it similarly affected the basal and final level but not the extent of the
      glucose-induced responses in derepressed cells. The reduction in growth rate
      caused by deletion of SCH9 is unlikely to be responsible for the increase in cAPK
      activity since reduction of growth rate generally leads to lower cAPK activity in
      yeast. On the other hand, deletion of SCH9 abolished the responses of the protein
      kinase A targets in glucose-repressed cells. Re-addition of nitrogen to cells
      starved for nitrogen in the presence of glucose failed to trigger activation of
      trehalase, caused strongly reduced and aberrant repression of CTT1 and SSA3, and
      failed to induce the upshift in RPL25 expression. From these results three
      conclusions can be drawn: (1) Sch9 either directly or indirectly reduces the
      activity of protein kinase A; (2) Sch9 is not required for glucose-induced
      activation of the Ras-adenylate cyclase pathway; and (3) Sch9 is required for
      nitrogen-induced activation of the FGM pathway. The latter indicates that Sch9
      might be the target of the FGM pathway rather than cAPK itself.

PMID- 9274017
TI  - The form of folate affects the mechanisms of methotrexate resistance in
      Enterococcus hirae [corrected].
AB  - Several mechanisms have been described to explain the resistance of cells to
      methotrexate (MTX); however, the basis for the heterogeneity of mechanisms has
      been obscure. It was hypothesized that the type of MTX resistance in a single
      species can be influenced by the form of extracellular folate supplied during the
      development of resistance. Two strains of MTX-resistant Enterococcus hirae
      [corrected] were developed by transferring the bacteria to media containing
      increasing concentrations of MTX in the presence of constant concentrations of
      either 5-formyl-5,6,7,8-tetrahydropteroylglutamic acid (5-HCO-H4PteGlu) or
      pteroylglutamic acid (PteGlu). These resistant strains were designated E.
      hirae/MTX/5-HCO-H4PteGlu and E. hirae/MTX/PteGlu, respectively [corrected]. The
      mechanisms of MTX resistance included: (1) increased folic acid reductase (FAR)
      activity in both resistant strains but increased dihydrofolate reductase (DHFR)
      activity only in E. hirae/MTX/PteGlu [corrected]; (2) decreased synthesis and
      intracellular retention of MTX containing two glutamyl residues; (3) decreased
      uptake of MTX accompanied by decreased uptake of folates; and (4) reduction of
      folate-binding capacity. Among these, the form of folate present in the media
      during the development of resistance affected DHFR and FAR activities and the
      transport of folates. These findings, together with data from other laboratories,
      suggest that it may be important to use a reduced form of folate, a more
      physiological form than oxidized PteGlu, in the media during the development of
      resistance for the study of the mechanisms of MTX resistance in cultured cells.

PMID- 9274018
TI  - A reassessment of the genetic determinants, the effect of growth conditions and
      the availability of an electron donor on the nitrosating activity of Escherichia
      coli K-12.
AB  - Anaerobic, but not aerobic, cultures of Escherichia coli K-12 catalysed the rapid
      nitrosation of the model substrate 2,3-diaminonaphthalene when incubated with
      nitrite. Formate and lactate were effective electron donors for the nitrosation
      reaction, which was inhibited by nitrate. Optimal growth conditions for the
      expression of nitrosation activity by various strains and mutants were
      determined. Highest activities were found with bacteria that had been grown
      anaerobically in a minimal medium rather than in Lennox broth, with glycerol and
      fumarate rather than glucose as the main carbon and energy source, and in the
      presence of a low concentration of nitrate. Bacteria harvested in the early
      exponential phase were more active than those harvested in later stages of
      growth. Well-characterized mutants defective in the synthesis of one or more
      anaerobically induced electron transfer chains were screened for nitrosation
      activity under these optimal growth conditions: only the respiratory nitrate
      reductase encoded by the narGHJI operon was implicated as a major contributor to
      nitrosation activity. Due to the limited sensitivity of the assays currently
      available, a minor contribution from the two alternative nitrate reductases or
      even other molybdoproteins could not be excluded. The role of formate in
      nitrosation was complex and was clearly not limited simply to that of an electron
      donor in the bacterial reduction of nitrite to nitric oxide: at least two
      further, chemical roles were inferred. This extensive study of more than 400
      independent cultures of E. coli K-12 and its derivatives resolved some, but not
      all, of the apparently conflicting data in the literature concerning nitrosation
      catalysed by enteric bacteria.

PMID- 9274019
TI  - Suppression of Escherichia coli formate hydrogenlyase activity by trimethylamine
      N-oxide is due to drainage of the inducer formate.
AB  - The effect of the addition of trimethylamine N-oxide (TMAO) in the growth medium
      on Escherichia coli anaerobic fermentative and respiratory pathways was examined.
      Formate dehydrogenase H (FDH-H) activity was totally repressed by the addition of
      40 mM TMAO, whereas the overall hydrogenase (HYD) activity was reduced by 25%.
      Accordingly, expression of lacZ operon fusions with the fdhF and hycB structural
      genes specifying FDH-H and HYD3 was reduced sevenfold and eightfold,
      respectively, leading to suppression of an active formate hydrogenlyase system.
      In contrast, global respiratory formate-dependent phenazine methosulphate
      reductase (FDH-PMS) activity, which consists of both the major anaerobic FDH-N
      enzyme and the aerobic FDH-Z isoenzyme, was increased approximately twofold. This
      was corroborated by a 2.5-fold stimulation of the sole fdoG-uidA transcriptional
      fusion which reflects the synthesis of the respiratory aerobic FDH-Z enzyme. In
      fdhD, fdhE or torA mutants lacking either FDH-PMS activity or TMAO reductase
      (TOR) activity, the formate hydrogenlyase pathway was no longer inhibited by
      TMAO. In addition, introduction of 30 mM formate in the growth medium was found
      to relieve the repressive effect of TMAO in the wild-type strain. When TMAO was
      added as terminal electron acceptor a significant enhancement of anaerobic growth
      was observed with the wild-type strain and the fdoG mutant. It was associated
      with the concomitant suppression of the formate hydrogenlyase enzymes. This was
      in contrast to the fdnG and torA mutants whose growth pattern and fermentative
      enzymes remained unaffected. Taken together, these results strongly suggest that
      formate-dependent reduction of TMAO via FDH-N and TOR reduces the amount of
      formate available for induction of the formate hydrogenlyase pathway.

PMID- 9274020
TI  - Salmonella typhi mutants defective in anaerobic respiration are impaired in their
      ability to replicate within epithelial cells.
AB  - By using MudJ (Kan, lac)-directed operon fusion technology, mutants of Salmonella
      typhi whose gene expression is induced under anaerobic growth conditions were
      isolated. Characterization of their phenotypes and regulatory properties revealed
      that two of the mutants were unable to use nitrate as a terminal electron
      acceptor in the absence of oxygen, suggesting that they were defective in nitrate
      reductase activity. Anaerobic induction of these fusions did not further increase
      in response to nitrate. Strains carrying an additional mutation in oxrA were
      constructed. They showed a lower level of beta-galactosidase expression both
      aerobically and anaerobically; however, the ratios of anaerobic induction
      remained unaltered. These MudJ insertions mapped to the 17-19 min region of the
      chromosome. Based upon their phenotypes and mapping, one of the mutants probably
      possessed a modC (chlD)::MudJ insertion and the other a moaA (chlA)::MudJ
      insertion. A third mutant was unable to use either nitrate or fumarate as a
      terminal electron acceptor. All three mutants showed a reduced ability to enter
      into and proliferate within HEp-2 epithelial cells. The oxrA mutation enhanced
      entry and proliferation of both the wild-type cells and the three mutants. Taken
      together, these results suggest that anaerobic respiration plays a role in S.
      typhi invasiveness.

PMID- 9274021
TI  - The Klebsiella pneumoniae cytochrome bd' terminal oxidase complex and its role in
      microaerobic nitrogen fixation.
AB  - Cytochrome bd' has been implicated in having an important role in microaerobic
      nitrogen fixation in the enteric bacterium Klebsiella pneumoniae, where it is
      expressed under all conditions that permit diazotrophy. In this paper the
      sequence of the genes encoding this terminal oxidase (cydAB) of Klebsiella
      pneumoniae and the characterization of a cyd mutant are reported. The deduced
      amino acid sequences support the proposal that His 19, His 186 and Met 393
      provide three of the four axial ligands to the Fe of the three haems in the
      oxidase complex. The nitrogen-fixing ability of the mutant was severely impaired
      in the presence of low concentrations of oxygen compared with the wild-type
      bacterium. Only the wild-type organism was capable of microaerobic nitrogenase
      activity supported by fermentation products. It is proposed that formate
      dehydrogenase-O may be involved in supplying electrons to a respiratory chain
      terminated by the bd-type oxidase, which would remove inhibitory oxygen and
      supply ATP for nitrogenase activity.

PMID- 9274022
TI  - Computer-based analyses of the protein constituents of transport systems
      catalysing export of complex carbohydrates in bacteria.
AB  - Bacteria synthesize and secrete an array of complex carbohydrates including
      exopolysaccharides (EPSs), capsular polysaccharides (CPSs), lipopolysaccharides
      (LPSs), lipo-oligosaccharides (LOSs) and teichoic acids (TCAs). We have analysed
      the families of homologous proteins that appear to mediate excretion of complex
      carbohydrates into or across the bacterial cell envelope. Two principal families
      of cytoplasmic-membrane transport systems appear to drive polysaccharide export:
      polysaccharide-specific transport (PST) systems and ATP-binding cassette-2 (ABC
      2) systems. We present evidence that the secretion of CPSs and EPSs, but not of
      LPSs, LOSs or TCAs via a PST or ABC-2 system requires the presence of a
      cytoplasmic-membrane-periplasmic auxiliary protein (MPA1 or MPA2, respectively)
      in both Gram-negative and Gram-positive bacteria as well as an outer-membrane
      auxiliary (OMA) protein in Gram-negative bacteria. While all OMA proteins are
      included within a single family, MPA1 and MPA2 family proteins are not
      demonstrably homologous to each other, even though they share common topological
      features. Moreover, MPA1 family proteins (which function with PST systems), but
      not MPA2 family proteins (which function with ABC-2 systems), possess cytoplasmic
      ATP-binding domains that may either exist as separate polypeptide chains (for
      those from Gram-positive bacteria) or constitute the C-terminal domain of the
      MPA1 polypeptide chain (for those from Gram-negative bacteria). The sizes,
      substrate specificities and regions of relative conservation and hydrophobicity
      are defined allowing functional and structural predictions as well as delineation
      of family-specific sequence motifs. Each family is characterized
      phylogenetically.

PMID- 9274023
TI  - Mycobacteriophage D29 contains an integration system similar to that of the
      temperate mycobacteriophage L5.
AB  - A mycobacteriophage D29 DNA fragment cloned in pRM64, a shuttle plasmid that
      transforms Mycobacterium smegmatis, was sequenced. The determined sequence was
      2592 nucleotides long and had a mean G+C content of 63.7 mol%, similar to that of
      mycobacterial DNA. Four ORFs were identified: one with strong homology to dCMP
      deaminase genes; one homologous to mycobacteriophage L5 gene 36, whose function
      is unknown; one encoding a possible excisase; and one encoding an integrase. The
      intergenic region between the putative excisase gene and the integrase gene had a
      lower than average G+C content and showed the presence of the same attP core
      sequence as mycobacteriophage L5. Transformation experiments using subclones of
      pRM64 indicated that the integrase gene and all the intergenic region were
      essential for stable transformation. A subclone containing the integrase gene and
      the core attP sequence was able to transform but recombinants were highly
      unstable. Southern analysis of total DNA from cells transformed with pRM64 and
      its derivatives showed that all the plasmids were integrated at one specific site
      of the bacterial chromosome. A recombinant exhibiting a high level of resistance
      to the selective drug kanamycin had two plasmids integrated at different sites.
      These results demonstrated that the D29 sequences contained in pRM64 were
      integrative, indicating that the generally hold view of D29 as a virulent phage
      must be reviewed.

PMID- 9274025
TI  - Expression of the eicosapentaenoic acid synthesis gene cluster from Shewanella
      sp. in a transgenic marine cyanobacterium, Synechococcus sp.
AB  - The eicosapentaenoic acid (EPA) synthesis gene cluster isolated from a marine
      bacterium, Shewanella putrefaciens strain SCRC-2738, was cloned and expressed in
      the marine cyanobacterium Synechococcus sp. A broad-host-range cosmid vector,
      pJRD215 (10.2 kb, Smr Kmr), was used to clone a 38 kb insert, pEPA, containing
      the EPA synthesis gene cluster, creating plasmid pJRDEPA (approx. 48 kb). This
      plasmid was transferred to the cyanobacterial host at a frequency of 2.2 x 10(
      7). Cyanobacterial transconjugants grown at 29 degrees C produced 0.12 mg EPA (g
      dry weight)-1, whereas those grown at 23 degrees C produced 0.56 mg EPA (g dry
      weight)-1. The yield was further improved to 0.64 mg (g dry weight)-1 by
      incubation for 1 d at 17 degrees C. This is believed to be the first successful
      cloning and expression of such a large heterologous gene cluster in a marine
      cyanobacterium.

PMID- 9274024
TI  - A Streptomyces griseus gene (sgaA) suppresses the growth disturbance caused by
      high osmolality and a high concentration of A-factor during early growth.
AB  - A-factor (2-isocapryloyl-3R-hydroxymethyl-gamma-butyrolactone), produced in a
      growth-dependent manner, switches on secondary metabolite formation and
      morphological differentiation in Streptomyces griseus, presumably by binding to
      the A-factor receptor protein (ArpA)-DNA complex and releasing the repression
      caused by ArpA. In the A-factor-deficient mutant strain S. griseus HH1 a large
      deletion includes afsA which is required for A-factor production. Growth and
      aerial mycelium formation of strain HH1 on media containing high concentrations
      of sucrose, sorbitol, mannitol, KCl or NaCl was disturbed by the presence of a
      large amount of A-factor supplied either exogenously or by a high-copy-number
      plasmid carrying afsA. This disturbance did not occur on media of normal
      osmolality and was observed only when A-factor was supplied during the very early
      stage of growth, about 8 h after inoculation. In addition, neither the wild-type
      strain nor S. griseus KM7 defective in ArpA exhibited the disturbance. These
      observations suggest that the presence of a large amount of A-factor during the
      very early stage of growth, probably during the A-factor-sensitive stage,
      triggered abrupt and disordered expression of some genes. The effect was
      apparently mediated through ArpA in the A-factor regulatory cascade and disturbed
      the physiology of strain HH1 under high osmolality. A gene that suppressed the
      disturbance was identified 5.5 kb upstream of the afsA locus in the wild-type
      strain. The gene, named sgaA, encoded a protein of 264 aa with a calculated
      molecular mass of 28 kDa.

PMID- 9274026
TI  - Efficient secretion of the model antigen M6-gp41E in Lactobacillus plantarum
      NCIMB 8826.
AB  - Four Lactobacillus strains (Lb. plantarum NCIMB 8826, Lb. paracasei LbTGS1.4, Lb.
      casei ATCC 393 and Lb. fermentum KLD) were tested for their ability to produce
      and secrete heterologous proteins. These strains were first screened with an
      alpha-amylase reporter under the control of a set of expression or
      expression/secretion signals from various lactic acid bacteria. With most of the
      constructions tested, the level of extracellular production was highest in Lb.
      plantarum NCIMB 8826, and lowest in Lb. paracasei LbTGS1.4. These two strains
      were next assayed using a model antigen consisting of the N-terminal part of the
      M6 protein from Streptococcus pyogenes fused to the linear epitope ELDKWAS from
      human immunodeficiency virus gp41 protein. Secretion of this heterologous protein
      was inefficient in Lb. paracasei LbTGS1.4, which accumulated a large
      intracellular pool of the unprocessed precursor, whereas Lb. plantarum NCIMB 8826
      was able to secrete the antigen to a level as high as 10 mg l-1.

PMID- 9274027
TI  - Spo0A represses transcription of the cry toxin genes in Bacillus thuringiensis.
AB  - The DNA regions upstream from the genes encoding polypeptides of Bacillus
      thuringiensis subsp. israelensis larvicidal crystals (cry4A, cry4B, cry11A)
      contain sequences with similarities to the spo0A box of Bacillus subtilis (or
      '0A' box) and the promoter recognized by the sigma H-associated RNA polymerase of
      B. subtilis. Expression of cry-lacZ transcriptional fusions was analysed in
      various B. thuringiensis genetic backgrounds. The early transcription of the
      toxin genes was not sporulation-dependent, whereas the late-stage expression at
      t4-6 was sigma E-dependent. Primer extension analysis confirmed that the cry4-
      and cry11-type toxin genes were weakly transcribed during the transition phase;
      expression analysis of a cry11A'-lacZ transcriptional fusion in B. subtilis
      sporulation mutants confirmed the involvement of the sigma H-RNA polymerase.
      Primer extension analysis showed that in B. thuringiensis subsp. israelensis, the
      cry4A and cry11A gene transcription observed at the end of the growth stage was
      turned off at the beginning of the sporulation phase. The DNA region located
      upstream from the cry11A gene promoter including the putative '0A' box was
      deleted. This led to a derepression of the expression of the cry11A operon. These
      results suggest that the cry4A, cry4B and cry11A toxin genes of B. thuringiensis
      subsp. Israelensis are transcribed during the transition phase by the RNA
      polymerase associated with the sigma H factor and are subject to Spo0A
      repression.

PMID- 9274028
TI  - Mutational analysis of the early forespore/mother-cell signalling pathway in
      Bacillus subtilis.
AB  - Intercellular communication is a crucial phenomenon during spore development in
      Bacillus subtilis. It couples the establishment of a compartment-specific genetic
      program to the transcriptional activity of a sigma factor in the other
      compartment. It also keeps sigma factor activation in register with the
      morphological process. This study used directed mutagenesis to analyse the
      pathway that couples sigma E activation in the mother-cell to activation of sigma
      F in the forespore following asymmetric septation. Targets for mutagenesis in
      SpoIIGA (the receptor) were chosen based on the predicted topology of the protein
      when associated with the cell membrane. The results showed that a residue near
      the N terminus (D6), predicted to be exposed outside the cell, is required for
      receptor activity, whereas the major extracellular loop (between membrane domains
      IV and V) is dispensable for function. In contrast, mutations in SpoIIR (the
      signal) that partially blocked protein release (but not membrane translocation)
      had no effect on signal transduction. These results do not rule out the
      possibility that uncharacterized molecules intervene in the signalling pathway
      that establishes the mother-cell-specific developmental program during the early
      stage of sporulation.

PMID- 9274029
TI  - Sequence and analysis of a 31 kb segment of the Bacillus subtilis chromosome in
      the area of the rrnH and rrnG operons.
AB  - A 31141 bp continuous nucleotide sequence in the region from trnl to pNEXT52 in
      the Bacillus subtilis 168 genome was determined. In the region, there were 22
      ORFs, two complete rRNA operons, and five tRNA genes. It was deduced that the
      function of one of the ORFs was similar to that of a sigma factor belonging to
      the ECF (extra-cytoplasmic functions) subfamily. The gene cluster feuA, B, C
      reported previously for other strains of B. subtilis was also found in strain 168
      and located in this region.

PMID- 9274030
TI  - Analysis of the Bacillus subtilis genome: cloning and nucleotide sequence of a 62
      kb region between 275 degrees (rrnB) and 284 degrees (pai).
AB  - In the framework of the international project aimed at the sequencing of the
      Bacillus subtilis genome, five DNA fragments in the region between rrnB (275
      degrees) and pai (284 degrees) were cloned by inverse and combinatorial long
      range PCR and their nucleotide sequences were determined and analysed. Together
      these sequences constituted a contig of 62229 bp. On the basis of the position of
      Not1 and Stil restriction sites, the orientation and order of known genetic
      markers was determined to be pai (284 degrees)-degQ comQ comP comAA comAB-pbpD
      kapB kinB patB-mcpB tipA mcpA tipB-rrnB (275 degrees). Fifty-four ORFs were
      detected. Thirteen of these coincided with known B. subtilis genes, and 41 new
      ORFs were found. Of the predicted new gene products, 12 showed no significant
      similarity to other known proteins, whereas ten showed strong similarity to
      proteins of other organisms with unknown function. Nineteen predicted proteins
      showed strong similarity to known proteins of other organisms, for instance a
      Na+/H+ antiporter system of Bacillus alcalophilus, a sugar transport system found
      in Mycoplasma genitalium, NADH-dependent butanol dehydrogenase of Clostridium
      acetobutylicum, glucose-6-phosphate isomerase A of B, subtilis, exo-1,4-alpha
      glucosidase activity of Bacillus stearothermophilus and L-rhamnose isomerase of
      Escherichia coli.

PMID- 9274031
TI  - A 32 kb nucleotide sequence from the region of the lincomycin-resistance gene (22
      degrees-25 degrees) of the Bacillus subtilis chromosome and identification of the
      site of the lin-2 mutation.
AB  - A 32 kb nucleotide sequence in the region of the lincomycin-resistance gene,
      located from 22 degrees to 25 degrees on the Bacillus subtilis chromosome, was
      determined. Among 32 putative ORFs identified, four [lipA for lipase, natA, natB
      and yzaE (renamed yccK)] have already been reported, although the functions of
      NatA, NatB and YccK remain to be characterized. Six putative products were found
      to exhibit significant similarity to known proteins in the databases, namely L
      asparaginase precursor, protein aspartate phosphatase, alpha-glucosidase, two
      tellurite-resistance proteins and a hypothetical protein from B. subtilis. The
      region of the tellurite-resistance gene, consisting of seven ORFs, seems to
      correspond to an operon. The products of 14 ORFs exhibited considerable or
      limited similarity to known proteins. The sequenced region seems to be rich in
      membrane proteins, since at least 16 gene products appeared to contain membrane
      spanning domains. The site of the lin-2 mutation (two nucleotide replacements)
      was mapped and identified by sequencing. This site is located between a putative
      promoter and the SD sequence of ImrA (yccB) [a putative repressor of the lmr
      operon, which consists of lmrA and lmrB (yccA)]. LmrB is a homologue of proteins
      involved in drug-export systems and seems likely to be the protein responsible
      for resistance to lincomycin.

PMID- 9274032
TI  - Genomic rearrangements during evolution of the obligate intracellular parasite
      Rickettsia prowazekii as inferred from an analysis of 52015 bp nucleotide
      sequence.
AB  - In this study a description is given of the sequence and analysis of 52 kb from
      the 1.1 Mb genome of Rickettsia prowazekii, a member of the alpha-Proteobacteria.
      An investigation was made of nucleotide frequencies and amino acid composition
      patterns of 41 coding sequences, distributed in 10 genomic contigs, of which 32
      were found to have putative homologues in the public databases. Overall, the
      coding content of the individual contigs ranged from 59 to 97%, with a mean of
      81%. The genes putatively identified included genes involved in the biosynthesis
      of nucleotides, macromolecules and cell wall structures as well as citric acid
      cycle component genes. In addition, a putative identification was made of a
      member of the regulatory response family of two-component signal transduction
      systems as well as a gene encoding haemolysin. For one gene, the homologue of
      metK, an internal stop codon was discovered within a region that is otherwise
      highly conserved. Comparisons with the genomic structures of Escherichia coli,
      Haemophilus influenzae and Bacillus subtilis have revealed several atypical gene
      organization patterns in the R. prowazekii genome. For example, R. prowazekii was
      found to have a unique arrangement of genes upstream of dnaA in a region that is
      highly conserved among other microbial genomes and thought to represent the
      origin of replication of a primordial replicon. The results presented in this
      paper support the hypothesis that the R. prowazekii genome is a highly derived
      genome and provide examples of gene order structures that are unique for the
      Rickettsia.

PMID- 9274033
TI  - Molecular characterization of the Serratia marcescens OmpF porin, and analysis of
      S. marcescens OmpF and OmpC osmoregulation.
AB  - Serratia marcescens is a nosocomial pathogen with a high incidence of beta-lactam
      resistance. Reduced amounts of outer-membrane porins have been correlated with
      increased resistance to beta-lactams but only one porin, OmpC, has been
      characterized at the molecular level. In this study we present the molecular
      characterization of a second porin, OmpF, and an analysis of the expression of S.
      marcescens porins in response to various environmental changes. Two porins were
      isolated from the outer membrane using urea-SDS-PAGE and the relative amounts
      were shown to be influenced by the osmolarity of the medium and the presence of
      salicylate. From a S. marcescens genomic DNA library an 8 kb EcoRI fragment was
      isolated that hybridized with an oligonucleotide encoding the published N
      terminal amino acid sequence of the S. marcescens 41 kDa porin. A 41 kDa protein
      was detected in the outer membrane of Escherichia coli NM522 carrying the cloned
      S. marcescens DNA. The cloned gene was sequenced and shown to code for a protein
      that shared 60-70% identity with other known OmpF and OmpC sequences. The
      upstream DNA sequence of the S. marcescens gene was similar to the corresponding
      E. coli ompF sequence; however, a regulatory element important in repression of
      E. coli ompF at high osmolarity was absent. The cloned S. marcescens OmpF in E.
      coli increased in expression in conditions of high osmolarity. The potential
      involvement of micF in the observed osmoregulation of S. marcescens porins is
      discussed.

PMID- 9274034
TI  - Heat shock response and groEL sequence of Bartonella henselae and Bartonella
      quintana.
AB  - Transmission of Bartonella species from ectoparasites to the mammalian host
      involves adaptation to thermal and other forms of stress. In order to better
      understand this process, the heat shock response of Bartonella henselae and
      Bartonella quintana was studied. Cellular proteins synthesized after shift to
      higher temperatures were intrinsically labelled with [25S]methionine and analysed
      by gel electrophoresis and fluorography. The apparent molecular masses of three
      of the major heat shock proteins produced by the two Bartonella species were
      virtually identical, migrating at 70, 60 and 10 kDa. A fourth major heat shock
      protein was larger in B. quintana (20 kDa) than in B. henselae (17 kDa). The
      maximum heat shock response in B. quintana and B. henselae was observed at 39
      degrees C and 42 degrees C, respectively. The groEL genes of both Bartonella
      species were amplified, sequenced and compared to other known groEL genes. The
      phylogenetic tree based on the groEL alignment places B. quintana and B. henselae
      in a monophyletic group with Bartonella bacilliformis. The deduced amino acid
      sequences of Bartonella GroEL homologues contain signature sequences that are
      uniquely shared by members of the Gram-negative alpha-purple subdivision of
      bacteria, which live within eukaryotic cells. Recombinant His6-GroEL fusion
      proteins were expressed in Escherichia coli to generate specific rabbit antisera.
      The GroEL antisera were used to confirm the identity of the 60 kDa Bartonella
      heat shock protein. These studies provide a foundation for evaluating the role of
      the heat shock response in the pathogenesis of Bartonella infection.

PMID- 9274035
TI  - A new nos gene downstream from nosDFY is essential for dissimilatory reduction of
      nitrous oxide by Rhizobium (Sinorhizobium) meliloti.
AB  - Rhizobium (Sinorhizobium) meliloti strains capable of dissimilatory nitrous oxide
      reduction (Nos+) carry a nosRZDFY gene cluster on a 10.1 kb EcoRI fragment of the
      nod megaplasmid near the fixGHIS genes. These nos genes are arranged in three
      complementation groups and the 10.1 kb EcoRI fragment is sufficient to confer Nos
      activity to R. meliloti strains lacking such activity. An overlapping HindIII
      fragment containing the nosRZDFY genes but missing a 0-6 kb HindIII-EcoRI
      downstream segment was found incapable of imparting Nos activity to strains
      unable to reduce nitrous oxide, suggesting the presence of other nos gene(s) in
      this region. Tn5 introduced near the HindIII site resulted in mutants with a Nos-
      phenotype. Complete sequence analysis of nosY showed that it was well-conserved
      with respect to that of Pseudomonas stutzeri. Two previously unreported genes
      downstream of nosY in R. meliloti were also revealed. Contiguous with nosY was a
      sequence showing 63% identity with the ORFL protein of P. stutzeri. It appeared
      to be in the same operon as nosDFY and was predicted to encode a membrane
      lipoprotein similar to the putative NosL of P. stutzeri. Unlike the latter
      protein, however, amino acid sequences typical of metal-binding sites and
      cysteine residues indicative of the active site of protein disulphide isomerase
      were absent in the predicted NosL of R. mellioti. The Tn5 mutations resulting in
      a Nos- phenotype were localized within a 966 nucleotide gene 31 nucleotides
      downstream of nosDFYL with the same orientation. The new gene, nosX, was
      determined to be in a separate complementation group. It encoded a periplasmic
      protein with homology in the C-terminal domain with Rnff of Rhodobacter
      capsulatus and with a hypothetical Escherichia coli protein, YOJK. It was
      concluded that there are seven genes constituting the nos cluster in R. meliloti.
      They are organized in four complementation groups and in the same orientation,
      spanning a distance of about 9 kb on the nod megaplasmid.

PMID- 9274036
TI  - Sequence, localization and characteristics of the replicator region of the
      symbiotic plasmid of Rhizobium etli.
AB  - The replicator region of the symbiotic plasmid of Rhizobium etli CFN42 was cloned
      and sequenced. A plasmid derivative (pH3) harbouring a 5-6 kb HindIII fragment
      from the symbiotic plasmid was found to be capable of independent replication and
      eliminated the symbiotic plasmid when introduced into a R. etli CFNX101 strain (a
      recA derivative). The stability and the copy number of pH3 were the same as that
      of the symbiotic plasmid, indicating that the information required for stable
      replication and incompatibility resides in the 5.6 kb HindIII fragment. The
      sequence analysis of this fragment showed the presence of three ORFs similar in
      sequence analysis of this fragment showed the presence of three ORFs similar in
      sequence and organization to repA, repB and repC described for the replicator
      regions of the Agrobacterium plasmids pTiB653 and pRiA4b and for the R.
      leguminosarum cryptic plasmid pRL8JI. Hybridization studies showed that p42d-like
      replicator sequences are found in the symbiotic plasmids of other R. etli strains
      and in a 'cryptic' plasmid of R. tropici.

PMID- 9274037
TI  - Group II intron from Pseudomonas alcaligenes NCIB 9867 (P25X): entrapment in
      plasmid RP4 and sequence analysis.
AB  - Pseudomonas alcaligenes NCIB 9867 (strain P25X), which grows on 2,5-xylenol and
      harbours the plasmid RP4, was mated with a plasmid-free derivative of Pseudomonas
      putida NCIB 9869, strain RA713, which cannot grow on 2,5-xylenol. Some RA713
      transconjugants, initially selected on 2,5-xylenol, were found to carry RP4
      plasmids that had acquired additional fragments (designated Xin) which ranged in
      size from 2 kb to approximately 26 kb instability of DNA inserts in RP4::Xin
      hybrid plasmids was observed. The smallest insert present in a stable RP4::Xin6
      hybrid plasmid, termed Xin6, yielded multiple bands when it was used as a probe
      with digested P25X chromosomal DNA. Sequence analysis of Xin6 led to the
      discovery of an open reading frame with homology to the maturases of group II
      introns. The Xin6 insert also exhibited several features characteristic of a
      group II intron. These included the presence of the consensus sequence GUGYG at
      the 5' and and RAY at the 3' end of the intron. RNA secondary structure modelling
      of Xin6 also revealed the presence of perfectly conserved domains V and VI.
      Differences were detected in the Xin6 hybridization profiles of several P25X
      catabolic mutants that have lost the ability to grow on 2,5-xylenol. In these
      mutants the loss of 2,5-xylenol degradative ability could be due to genome
      rearrangements mediated by sequences related to the Xin6 group II intron. This is
      the first reported group II intron isolated from Pseudomonas spp. and the first
      time that the mobility of a bacterial group II intron has been demonstrated.

PMID- 9274038
TI  - Genetic relationships among Pasteurella trehalosi isolates based on multilocus
      enzyme electrophoresis.
AB  - Genetic diversity among 60 British Pasteurella trehalosi isolates representing
      the four recognized capsular serotypes, T3, T4, T10 and T15, and recovered
      predominantly from sheep suffering from systemic pasteurellosis, was estimated by
      analysing electrophoretically demonstrable allelic variation at structural genes
      encoding 19 enzymes. Thirteen of the locl were polymorphic and 20 distinctive
      multilocus genotypes (electrophoretic types, ETs) were identified. The population
      structure of P. trehalosi is clonal and its genetic diversity is limited compared
      with most other pathogenic bacteria. ETs represent clones, and isolates of the
      same ET were generally associated with the same combination of serotype, LPS type
      and outer-membrane protein (OMP) type. The genetic diversity of isolates within
      each of the capsular serotypes varied. Serotype T10 was represented by 18
      isolates in two related ETs and exhibited little diversity. By contrast, serotype
      T15 was represented by 18 isolates in nine ETs and was almost as diverse as the
      species as a whole Serotype T4 was represented by 18 isolates in five ETs and was
      less diverse than serotype T15. Although serotype T3 was more diverse than
      serotype T15 it was represented by only three isolates. With the exception of the
      T10 isolates and those recovered from healthy sheep, 35 disease isolates belonged
      to 16 ETs, each of which was represented by only one to four isolates. The fact
      that a high proportion of disease is caused by a relatively large number of
      clones suggests that P. trehalosi is essentially an opportunistic pathogen. In
      addition to having the same capsular structure, isolates belonging to the two T10
      clones were characterized by possession of similar, if not identical, O-antigens
      (LPS types 2 and 4). The occurrence of 18 serotype T10 isolates in only two ETs
      suggests that the T10 capsule and type 2/4 O-antigen confer enhanced virulence on
      members of these two clones. Multilocus enzyme electrophoresis (MLEE) had greater
      resolving power than did capsule/LPS/OMP analysis, being able to distinguish 20
      rather than 14 sub-divisions within P. trehalosi. The technique demonstrated
      genetic identity or non-identity among strains of the same or different serotypes
      from different geographic localities within the UK and was a useful
      epidemiological tool.

PMID- 9274039
TI  - In search of AIDS-resistance genes.

PMID- 9274040
TI  - Building doors into cells.

PMID- 9274041
TI  - Creating false memories.

PMID- 9274042
TI  - Axenic aerobic biofilms inhibit corrosion of SAE 1018 steel through oxygen
      depletion.
AB  - Corrosion inhibition of SAE 1018 steel by pure-culture biofilms of Pseudomonas
      fragi and Escherichia coli DH5 alpha has been evaluated in complex Luria-Bertani
      medium, seawater-mimicking medium, and modified Baar's medium at 30 degrees C. In
      batch cultures, both bacteria inhibited corrosion three to six fold compared to
      sterile controls, and the corrosion was comparable to that observed in anaerobic
      sterile media. To corroborate this result, a continuous reactor and
      electrochemical impedance spectroscopy were used to show that both P. fragi K and
      E. coli DH5 alpha decreased the corrosion rate by 4- to 40-fold as compared to
      sterile controls; this matched the decrease in corrosion found with sterile
      medium in the absence of oxygen and with E. coli DH5 alpha grown anaerobically.
      In addition, the requirement for live respiring cells was demonstrated by the
      increase in the corrosion rate that was observed upon killing the P. fragi K
      biofilm in continuous cultures, and it was shown that fermentation products do
      not cause an increase in corrosion. Hence, pure-culture biofilms inhibit
      corrosion of SAE 1018 steel by depleting oxygen at the metal surface.

PMID- 9274043
TI  - Characterization and optimization of a two-phase partitioning bioreactor for the
      biodegradation of phenol.
AB  - A two-phase partitioning bioreactor containing Pseudomonas putida ATCC 11172 was
      used to degrade high concentrations of phenol in batch and fed-batch mode. The 2
      1 (nominal volume) partitioning bioreactor employs a 1-1 cell-containing aqueous
      phase, and a 500-ml immiscible and biocompatible second organic phase (2
      undecanone), which partitions the toxic substrate into the aqueous phase at a
      rate based on the metabolic activity of the microorganisms. Using this reactor
      configuration, operated in batch mode, 10-g phenol was degraded to completion
      within 84-h. The system was, however, oxygen-limited during the rapid growth
      phase of the fermentation. A second experiment, using enriched air to prevent
      oxygen limitation, resulted in the complete degradation of 10-g phenol within 72
      h. The use of a sequential feeding strategy, in which a 10-g phenol load was
      added in sequential 5-g aliquots, resulted in a significant reduction in the lag
      phase, from 36-h to 12-h, and the consumption of 10-g phenol in 60 h. Finally,
      fed-batch fermentation was used to attempt to determine the ultimate capacity of
      the system to degrade phenol. The organic phase was loaded with 10-g phenol, the
      microorganisms were allowed to consume this aliquot almost to completion, and a
      second 10-g aliquot was then added. The organic phase was spiked in this manner a
      total of four times, resulting in the degradation of 46.55-g phenol within 12
      days. The system was also monitored for nutrient depletion, and a nutrient
      feeding schedule was formulated, in response to the mass of phenol consumed.

PMID- 9274044
TI  - Effect of soybean oil and glucose on sophorose lipid fermentation by Torulopsis
      bombicola in continuous culture.
AB  - The effect of soybean oil and glucose on the growth of Torulopsis bombicola and
      sophorose lipid production in continuous culture was investigated. As the
      dilution rate in 100 g/l glucose and 100 g/l soybean oil medium was increased,
      the dry cell weight and sophorose lipid concentration decreased. Sophorose lipid
      productivity, however, was maximum at a dilution rate of 0.03 h-1. The cell yield
      from glucose and the sophorose lipid production from soybean oil were
      approximately constant regardless of the dilution rate. The specific consumption
      rate of soybean oil was closely related to the specific production rate of
      sophorose lipid. These results suggest that soybean oil was used only for
      sophorose lipid production whereas glucose was used only for cell mass and
      maintenance. When the soybean oil concentration was varied at fixed dilution rate
      in 100 g/l glucose medium, a high concentration of soybean oil was found to
      inhibit sophorose lipid production.

PMID- 9274046
TI  - Reactivation of thermally inactivated enzymes by free and immobilized chaperonin
      GroEL/ES.
AB  - Thermally inactivated bovine deoxyribonuclease I (DNase I) and yeast enolase were
      reactivated by GroEL/ES from Escherichia coli. In both cases, GroEL/ ES was found
      to have the ability to reactivate inactivated enzymes in an ATP-dependent manner.
      GroEL/ ES can interact with the enzymes that were denatured at high temperature
      and convert them to the active conformations. To test the applicability of
      GroEL/ES to the reactivation processes of thermally inactivated enzymes, GroEL/ES
      was immobilized using formyl-Cellulofine (GroEL/ES-Cellulofine) and its
      performance was studied. GroEL/ES-Cellulofine retained a sufficiently high
      ability to reactivate enzymes. Moreover, GroEL/ES-Cellulofine could be used
      repeatedly, indicating high durability. These results indicate that immobilized
      chaperonin is effective for reactivation of enzymes that are thermally
      inactivated in various bioprocesses.

PMID- 9274045
TI  - Purification and characterization of a glutamic-acid-specific endopeptidase from
      Bacillus subtilis ATCC 6051; application to the recovery of bioactive peptides
      from fusion proteins by sequence-specific digestion.
AB  - Screening cultures of nonpathogenic microorganisms led us to a glutamic-acid
      specific endopeptidase from Bacillus subtilis ATCC 6051, which we purified and
      named BSase. The nucleotide sequence encoding BSase, with a molecular mass of
      23,894 Da, completely agreed with that of the mpr gene, which had been reported
      by Rufo Jr. and Sloma et al. to encode a metalloprotease [J Bacteriol (1990) 172:
      1019-1023 and 1024-1029 respectively]. However, enzymatic characterization
      revealed it to have the catalytic triad of a serine protease and not the
      consensus sequence of a metalloprotease, and it was inhibited by
      diisopropylfluorophosphate. We therefore consider BSase (mpr) to be a serine
      protease. In the alignment of the acidic-amino-acid-specific proteases, the
      proteases from bacilli have a highly conserved histidine residue, which is most
      important in the histidine triad in the proteases from streptomycetes.
      Furthermore, Ca2+ was necessary for its activity and stability. BSase cleaved the
      C-terminal glutamic acid with high specificity and was very stable over a wide pH
      range. On the basis of these properties, we tried to retrieve a bioactive peptide
      from a fusion protein by sequence-specific digestion, and succeeded in obtaining
      the bioactive peptide. BSase was found to be very useful as a tool for selective
      cleavage.

PMID- 9274048
TI  - Efficient synthesis of the blood-coagulation inhibitor hirudin in the filamentous
      fungus Acremonium chrysogenum.
AB  - The isopenicillin-N-synthetase-encoding pcbC gene from the filamentous fungus
      Acremonium chrysogenum is differentially expressed in strains showing either a
      high or low cephalosporin C production. For a case study to demonstrate
      heterologous protein synthesis in A. chrysogenum, we have chosen a synthetic 195
      bp gene encoding the thrombin inhibitor hirudin from the leech Hirudo
      medicinalis. The hirudin gene was fused with the 5' and 3' regions of the pcbC
      gene, resulting in four different expression vectors, which we named pHIR1 to
      pHIR4. In order to achieve secretion of the heterologous polypeptide, two out of
      four vectors carry, in addition, secretion signal sequences of an alkaline
      protease gene originating either from Fusarium sp. or from A. chrysogenum. After
      DNA-mediated transformation of the two A. chrysogenum strains, transformants were
      further analysed on the transcriptional and translational level. Irrespective of
      the vector used for transformation, all transformants show a hirudin-gene
      specific transcript in Northern hybridizations. In further analysis, hirudin
      synthesis was determined with a thrombin-inhibition assay, but was detectable
      only in those strains carrying expression plasmids with the secretion signals. In
      this case, hirudin was secreted into the culture medium. Transformants from
      strains with a high cephalosporin C production showed a three- to eightfold
      higher expression of the hirudin gene compared to low cephalosporin-C-producing
      strains. The amount of recombinant hirudin was quantified further by ELISA and
      Western blotting, using a monoclonal antibody directed against recombinant
      hirudin. Finally, the time course of hirudin gene expression was investigated in
      a selected transformant that has hirudin activities of 8.0 ATU/ml culture medium.
      Northern hybridization experiments revealed the highest hirudin transcript level
      after 2-5 days of cultivation, showing the strongest signal after 3 days. After 4
      5 days, we detected the highest hirudin activity, as was confirmed by Western
      blotting. The level of heterologous hirudin synthesis in A. chrysogenum is
      discussed in relation to other eukaryotic expression systems.

PMID- 9274047
TI  - Mannitol dehydrogenase from Rhodobacter sphaeroides Si4: subcloning,
      overexpression in Escherichia coli and characterization of the recombinant
      enzyme.
AB  - By polymerase chain reaction mutagenesis techniques, an NdeI restriction site was
      introduced at the initiation codon of the mannitol dehydrogenase (MDH) gene
      (mtlK) of Rhodobacter sphaeroides Si4. The mtlK gene was then subcloned from
      plasmid pAK74 into the NdeI site of the overexpression vector pET24a+ to give
      plasmid pASFG1. Plasmid pASFG1 was introduced into Escherichia coli BL21(DE3),
      which was grown in a 1.5-1 bioreactor at 37 degrees C and pH 7.0. Overexpression
      of MDH in Escherichia coli BL21(DE3) [pASFG1] was determined by enzymatic
      analysis and sodium dodecyl sulfate (SDS)/polyacrylamide gel electrophoresis.
      Under standard growth conditions, E. coli produced considerable amounts of a
      polypeptide that correlated with MDH in SDS gels, but the activity yield was low.
      Decreasing the growth temperature to 27 degrees C and omitting pH regulation
      resulted in a significant increase in the formation of soluble and enzymatically
      active MDH up to a specific activity of 12.4 U/mg protein and a yield of 26,000
      U/l, which corresponds to 0.38 g/l MDH. This was an 87-fold overexpression of MDH
      compared to that of the natural host R. sphaeroides Si4, and a 236-fold
      improvement of the volumetric yield. MDH was purified from E. coli BL21(DE3)
      [pASFG1] with 67% recovery, using ammonium sulfate precipitation, hydrophobic
      interaction chromatography, and gel filtration. Partial characterization of the
      recombinant MDH revealed no significant differences to the wild-type enzyme.

PMID- 9274049
TI  - Optimization of the solubilization and renaturation of fish growth hormone
      produced by Escherichia coli.
AB  - Growth hormone (GH) enhances the growth rate of aquacultured fish and shellfish,
      but it is difficult to extract native GH from fish pituitary glands. However,
      fish recombinant GH (rGH) can be efficiently synthesized by Escherichia coli
      cells, although it exists in denatured form in inclusion bodies (IB). We studied
      the solubilization of IB and the renaturation of rGH to help facilitate the
      production of a large amount of biologically active rGH. A 100-ml sample of rGH
      producing E. coli produced 73.43 +/- 5.47 mg IB (dry weight, n = 3) after 20 h
      induction by 1 mM isopropyl beta-o-thiogalactopyranoside. Interestingly, if the
      bacteria were induced by 0.1 mM beta-lactose, 95.3 +/- 3.43 mg of IB was
      obtained. The optimal conditions for denaturation and renaturation of rGH were
      when IB were solubilized in 6 M guanidine hydrochloride and then dialysed against
      pH 10 dialysis buffer (50 mM ammonium bicarbonate and 2 mM EDTA) containing 100
      mM L-arginine, 2 mM oxidized glutathione and 2 mM reduced glutathione for 24 h at
      4 degrees C in a volume ratio of 3 to 500. At least 20% of the denaturated rGH in
      IB was renatured. Juvenile black sea bream injected with 0.05 microgram/g
      resultant rGH once every 2 weeks exhibited significant increases (P < 0.05) in
      weight gain (84%) relative to fish in the control group over a 16-week period.
      This process is an economical and effective way to obtain an active form of rGH
      biosynthesized by a prokaryotic system.

PMID- 9274050
TI  - Comparison of partial 16S rRNA gene sequences obtained from activated sludge
      bacteria.
AB  - The cultivated and uncultivated bacterial communities of an activated sludge
      plant were studied. Two samples were taken and a total of 516 bacterial isolates
      were classified into groups using their whole-cell protein patterns. The
      distribution of bacteria into protein-pattern groups differed significantly
      between the two samples, suggesting variation in culturable bacterial flora.
      Partial 16S rRNA gene sequences were determined for representatives of the
      commonest protein-pattern groups. Most of the sequences obtained were previously
      unknown, but relatively closely related to known sequences of organisms belonging
      to the alpha, beta or gamma subclasses of the proteobacteria, the first two
      subclasses being predominant. This classification of bacteria isolated on a
      diluted nutrient-rich medium differed from recent culture-dependent studies using
      nutrient-rich media. The uncultivated bacterial community was studied by
      analyzing ten partial 16S rRNA gene sequences cloned directly from activated
      sludge. None of the cloned sequences was identical to those determined for
      culturable organisms; or to those in the GenBank database. They were, however,
      related to the alpha or beta subclasses of the proteobacteria, or to the gram
      positive bacteria with a high G + C DNA content.

PMID- 9274051
TI  - Biotransformation of linoleic acid with the Candida tropicalis M25 mutant.
AB  - Linoleic acid was transformed by mutant Candida tropicalis M25 and
      transformations were studied in batch and fed-batch cultures. Cofermentations
      with palmitic acid as inducer of the fatty acid degradation pathway were
      performed. Besides the (Z),(Z)-octadeca-6,9-dienedioic acid, (Z),(Z)-3
      hydroxyoctadeca-9,12-dienedioic acid and (Z),(Z)-3-hydroxytetradeca-5,8
      dienedioic acid were obtained as the main fermentation products. The maximum
      concentrations of (Z),(Z)-octadeca-6,9-dienedioic acid and (Z),(Z)-3
      hydroxyoctadeca-9,12-dienedioic acid reached values of 6.4 g/l and 6.9 g/l
      respectively. The structures of the products were characterized by chemical and
      spectroscopic methods. The configuration of the double bonds was not changed
      during bioconversion. As only one regioisomer of the hydroxylated fatty acid was
      detected, the hydroxylation is site-specific.

PMID- 9274053
TI  - Creating auxotrophic mutants in Methylophilus methylotrophus AS1 by combining
      electroporation and chemical mutagenesis.
AB  - Stable auxotrophic mutants of the methylotroph Methylophilus methylotrophus AS1
      were obtained by a novel mutagenesis technique in which electroporation is used
      to transport the chemical mutagen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)
      across the cell membrane. By combining chemical mutagenesis with electroporation
      and screening single colonies for auxotrophy in 36 different amino acids and
      growth factors, 3 auxotrophs per 156 colonies screened were obtained, whereas no
      auxotrophs were found with chemical mutagenesis alone. MNNG mutagen toxicity was
      also increased in the methylotroph with this novel mutagenesis technique (death
      rate 96% compared to 79%). This technique did not increase the mutation rate for
      strain Escherichia coli BK6 which responds well to simple exposure to the
      mutagen.

PMID- 9274052
TI  - Effect of the addition of Peptostreptococcus productus ATCC35244 on the gastro
      intestinal microbiota and its activity, as simulated in an in vitro simulator of
      the human gastro-intestinal tract.
AB  - Peptostreptococcus productus ATCC35244, a reductive acetogenic strain, was added
      daily over 9 successive days to the fourth vessel (ascending colon) of the SHIME,
      a six-stage reactor system simulating the in vivo continuous culture conditions
      of the human gastro-intestinal tract. Final numbers of organisms (cfu)/ml reactor
      contents (c) were attained such that log10c = 6.9 +/- 0.1. The addition caused
      the CH4 production to decrease below the detection limit while total gas and CO2
      production in the fifth (transverse colon) and sixth reactor (descending colon)
      were lowered and the acetic acid concentration was augmented. Ending the
      supplementation caused CH4 production to re-establish within 4 days, while CO2
      production increased much more slowly. The concentration of acetic acid only
      started to decrease after 7 days. The results indicate that P. productus, upon
      regular administration, is able to compete with methanogens for H2 in the gastro
      intestinal microbial ecosystem because of its reductive acetogenic character.

PMID- 9274054
TI  - Thermophilic biodegradation of BTEX by two consortia of anaerobic bacteria.
AB  - Two thermophilic anaerobic bacterial consortia (ALK-1 and LLNL-1), capable of
      degrading the aromatic fuel hydrocarbons, benzene, toluene, ethylbenzene, and the
      xylenes (BTEX compounds), were developed at 60 degrees C from the produced water
      of ARCO'S Kuparuk oil field at Alaska and the subsurface water at the Lawrence
      Livermore National Laboratory gasoline-spill site, respectively. Both consortia
      were found to grow at 45-75 degrees C on BTEX compounds as their sole carbon and
      energy sources with 50 degrees C being the optimal temperature. With 3.5 mg total
      BTEX added to sealed 50-ml serum bottles, which contained 30 ml mineral salts
      medium and the consortium, benzene, toluene, ethylbenze, m-xylene, and an
      unresolved mixture of o- and p-xylenes were biodegraded by 22%, 38%, 42%, 40%,
      and 38%, respectively, by ALK-1 after 14 days of incubation at 50 degrees C.
      Somewhat lower, but significant, percentages of the BTEX compounds also were
      biodegraded at 60 degrees C and 70 degrees C. The extent of biodegradation of
      these BTEX compounds by LLNL-1 at each of these three temperatures was slightly
      less than that achieved by ALK-1. Use of [ring-14C]toluene in the BTEX mixture
      incubated at 50 degrees C verified that 41% and 31% of the biodegraded toluene
      was metabolized within 14 days to water-soluble products by ALK-1 and LLNL-1,
      respectively. A small fraction of it was mineralized to 14CO2. The use of [U
      14C]benzene revealed that 2.6%-4.3% of the biodegraded benzene was metabolized at
      50 degrees C to water-soluble products by the two consortia; however, no
      mineralization of the degraded [U-14C]benzene to 14CO2 was observed. The
      biodegradation of BTEX at all three temperatures by both consortia was tightly
      coupled to sulfate reduction as well as H2S generation. None was observed when
      sulfate was omitted from the serum bottles. This suggests that sulfate-reducing
      bacteria are most likely responsible for the observed thermophilic biodegradation
      of BTEX in both consortial cultures.

PMID- 9274055
TI  - Construction of a psb C deletion strain in Synechocystis 6803.
AB  - Synechocystis 6803 is a cyanobacterium that carries out-oxygenic photosynthesis.
      We are interested in the introduction of mutations in the large extrinsic loop
      region of the CP43 protein of Photosystem II (PSII). CP43 appears to be required
      for the stable assembly of the PSII complex and also appears to play a role in
      photosynthetic oxygen evolution. Deletion of short segments of the large
      extrinsic loop results in mutants incapable of evolving oxygen. Alterations in
      psbC, the gene encoding CP43, are introduced into Synechocystis 6803 by
      transformation and homologous recombination. Specifically, plasmid constructs
      bearing the site-directed mutations are introduced into a deletion strain where
      the portion of the gene encoding the area of mutation has been deleted and
      replaced by a gene conferring antibiotic resistance. We have constructed a
      deletion strain of Synechocystis appropriate for the introduction of mutations in
      the large extrinsic loop of CP43 and have used it successfully to produce site
      directed mutants.

PMID- 9274056
TI  - Molecular approaches to identify novel genes expressed in Arabidopsis thaliana.
AB  - Our laboratory is engaged in an effort to identify genes expressed primarily
      during plant embryogenesis. Genes which exhibit unique expression profiles in the
      plant are also being sought. To this end, several methods to identify and clone
      novel genes based on specific expression patterns have been developed. These
      methods include virtual subtraction, differential display and other PCR based
      technologies. In addition to this, a yeast one-hybrid approach has been
      established to identify transcription factors which regulate these genes. To
      date, this work has identified several novel genes.

PMID- 9274057
TI  - The biosynthetic incorporation of selenomethionine and telluromethionine into
      pyrrolidone carboxyl peptidase (PYRase) from S. aureus.
AB  - Heavy-atom derivatives of PYRase proteins prepared in the past have been
      unsuitable for x-ray diffraction analysis. Thus, we propose utilizing unnatural
      metalloid-containing amino acids as an alternative to heavy-atom derivatization.
      Selenomethionine-containing proteins analyzed by multiwavelength anomalous
      diffraction provides a facile means of addressing the phase problem, whose
      solution is necessary to determine protein structures by X-ray Crystallography
      [Hendrickson, et al., 1991 and references therein]. Telluromethionine-containing
      proteins offer the same investigational potential, and additionally allow further
      simplification of the data collection technique by requiring only traditional
      methods of phase analysis [Boles et al., 1995 and references therein]. We sought
      to introduce the required Se and Te atoms into Staphylococcus aureus Pyrrolidone
      Carboxyl Peptidase (PYRase) via selenomethionine (SeMet) and telluromethionine
      (TeMet). Complete incorporation of SeMet into S. aureus PYRase was succeeded with
      little change in enzymatic properties. Incomplete incorporation (75%) of TeMet
      was accomplished in preparing TeMet-PYRase, however, representing the highest
      incorporation to date of a tellurium-containing amino acid. Enzymatic properties
      remained unchanged when TeMet was incorporated. We report herein the biosynthetic
      substitution and expression, protein purification and comparative biochemistry of
      SeMet-PYRase and TeMet-PYRase.

PMID- 9274058
TI  - Plasticity of cardiovascular nucleoside transporters following chronic
      dipyridamole treatment.
AB  - Dipyridamole (37.5 mg/kg, s.c., b.i.d.), a potent inhibitor of nucleoside
      transport, was administered to guinea pigs for 14 days in order to investigate
      the effects of: 1) chronic dipyridamole treatment on [3H]nitrobenzylthioinosine
      ([3H]NBMPR) binding: 2) chronically released endogenous adenosine on adenosine A1
      and A2 receptors. Comparisons of the binding capacities (Bmax) and equilibrium
      dissociation constants (Kd) in vehicle-treated (VTA) and dipyridamole-treated
      animals (DTA), revealed a 100 percent increase in Kd of [3H]NBMPR binding in the
      kidney of DTA but not in heart or brain. There were no changes in adenosine A1 or
      A2 receptor activities in kidney and brain as measured by [3H]R
      phenylisopropyladenosine and [3H]5'-N-ethyl-carboxamidoadenosine binding,
      respectively. The data suggest that cardiac and central nucleoside transporters
      may be either less susceptible to chronic dipyridamole administration or have a
      different adaptive mechanism. Also, endogenous adenosine, which may be
      chronically released upon dipyridamole treatment, has no effect on adenosine
      receptors.

PMID- 9274059
TI  - Genetic manipulation of anaerobic cellulolytic bacteria.
AB  - Transposon Tn1545 was introduced into the chromosome of the ruminal cellulolytic
      bacterium Eubacterium cellulosolvens. This was achieved by conjugal transfer of
      the transposon from Clostridium beijerinckii at a frequency of about 1 per 10(4)
      recipient cells. Transconjugants of E. cellulosolvens were resistant to both
      tetracycline and erythromycin. E. cellulosolvens could also serve as a donor for
      conjugal transfer of Tn1545 back into C. beijerinckii.

PMID- 9274060
TI  - Bombyxin: an insect neurohormone targets the ovaries in Lepidoptera.
AB  - Bombyxin, an insect hormone structurally related to insulin, was chemically
      synthesized and defined radioactively labeled probes were generated in order to
      detect and characterize bombyxin receptors in insect tissue. In all species
      tested, Bombyx mori (silkmoth), Samia cynthia ricini (Ailanthus moth). Manduca
      sexta (tobacco hornworm) and Spodoptera frugiperda (fall armyworm), bombyxin
      receptors were found in ovaries. A radioactive photolabeled bombyxin analog was
      crosslinked to the potential bombyxin receptor and the hormone-receptor complex
      identified by SDS PAGE. The bombyxin-receptor has an apparent molecular mass of
      about 300 kDa which after reduction forms a binding subunit of 90 to 110 kDa. The
      presence of bombyxin-receptors on ovaries suggests a function of this hormone in
      reproduction.

PMID- 9274061
TI  - Genetic approaches to biochemical questions: insights into the functional
      requirements of proline 185 in the active site of human galactose-1-phosphate
      uridylyltransferase.
AB  - Saturating random mutagenesis at a given position within a polypeptide sequence
      can provide powerful insights into the functional requirements of the position.
      By coupling this genetic methodology with expression of human proteins in yeast,
      we and others have begun to ask pointed and important questions about the
      structure-function relationships of proteins associated with human genetic
      disease.

PMID- 9274062
TI  - Structure of the Haemophilus influenzae uvr-1+ gene: homology with other uvrC
      like genes and characterization of the Haemophilus influenzae uvr-1 and uvr-2
      mutations.
AB  - A 3.9 kb Haemophilus influenzae genomic DNA fragment was cloned in plasmid pUC9
      that partially complemented the ultraviolet light sensitivity (UVs) of
      Escherichia coli uvrC mutant hosts. This fragment also complemented the UVs of H.
      influenzae uvr-1 (DB112) and uvr-2 (DB116) mutants. It genetically transformed
      the latter mutants to wild type UV resistance. The nucleotide (nt) sequence of
      this fragment revealed 3 open reading frames (ORFs). ORF2, now designated uvr-1+
      (1746 nt), shows significant similarity in both the nt and amino acid (aa)
      composition to 7 complete proven or putative uvrC gene sequences. Computer
      analysis of the DNA sequence revealed several possible regulatory motifs 5' to
      uvr-1+, including a putative LexA-binding site as an inverted SOS box, located
      within the 3' region of ORF1, (extensive homology to the E. coli CMP-KDO
      synthetase gene), upstream of uvr-1+. Further computer analysis has also
      predicted that the four putative active site amino acids, located in the C
      terminal half of each protein, are each situated in an area of secondary
      structure that are highly conserved.

PMID- 9274063
TI  - Mattress replacement or foam overlay? A prospective study on the incidence of
      pressure ulcers.
AB  - The purpose of this study was to compare the incidence of pressure ulcers in 40
      newly admitted at-risk (Braden Scale score < 18) skilled-nursing-facility
      residents, randomly assigned to Iris 3000 (Bio Clinic of Sunrise Medical Corp,
      Ontario, CA) foam mattress overlays (n = 20) or a MAXIFLOAT (BG Industries,
      Northridge, CA) foam mattress replacements (n = 20). Head-to-toe skin assessments
      were done 3 times weekly for a maximum of 21 days, using Bergstrom Skin
      Assessment Tool. Subjects on MAXIFLOAT had fewer pressure ulcers (chi 2[1, N =
      40] = 5.013, p = .025) despite heavier body mass (t[35] = 2.60, p = .013) and
      more days on the surface (t[38] = 2.24, p = .03). MAXIFLOAT proved to be more
      effective in preventing pressure ulcers in an at-risk skilled-care population and
      was cost-effective. Research findings on efficacy, adequate feedback from nursing
      staff, residents, and ancillary staff regarding issues of patient comfort, ease
      of use, and cost are important factors in decision-making when considering
      product changes.

PMID- 9274064
TI  - Testing a community level research utilization intervention.
AB  - Research supports changing practice from heparinized to saline flushes for
      adults, yet heparin continues to be used in clinical practice. The primary aim of
      this study was to test the effectiveness of a community level innovation
      diffusion intervention as a method of stimulating research utilization at three
      acute care facilities in one community simultaneously. The change advocated was
      the flushing of intermittent intravenous devices (IID) with saline rather than
      heparin. Pilot IID units were chosen on which to test the change from the use of
      heparin to saline flushes. The innovation focused on staff empowerment and was
      implemented in five phases. The change to saline flushes was successful and has
      been maintained.

PMID- 9274065
TI  - The Open Window Phase: helpseeking and reality behaviors by battered women.
AB  - Battered women are trapped in a cycle of violence that is difficult to break. The
      purpose of this study was to determine when helpseeking and reality behaviors
      were most likely to be exhibited by battered women. The results of this study
      revealed a period of helpseeking and reality behaviors by battered women
      occurring in a cyclical pattern within the cycle of violence. The author named
      this period the Open Window Phase. This phase may be seen as a crucial
      opportunity for successful intervention in the lives of battered women and a
      positive step toward breaking the cycle of violence.

PMID- 9274066
TI  - Chest pain and cocaine use in 18 to 40 year-old persons: a retrospective study.
AB  - This study examined the incidence of chest pain and cocaine use in 18 to 40 year
      olds who were seen in a public inner city emergency department. The medical
      records of a convenience sample of 386 subjects were reviewed during a 6 month
      period. Results revealed a significant differences in physiological, diagnostic,
      and patient history data associated with chest pain and cocaine use. These data
      that highlight the clinical features of cocaine users can be used as a profile
      for the management of cocaine-related cardiovascular problems.

PMID- 9274067
TI  - The assessment of acute confusion as part of nursing care.
AB  - Older adults who become acutely confused when hospitalized present challenges to
      nurses because of their increased care needs and risk for injury. This study
      evaluated the feasibility of introducing the NEECHAM Confusion Scale as part of
      usual nursing care as a first step in improving nurses' ability to assess,
      prevent, and manage acute confusion in hospitalized older adults. By addressing
      several of the factors that influence adoption and continuation of a new
      practice, this study found that staff nurses could successfully use the NEECHAM
      Confusion Scale.

PMID- 9274068
TI  - Recruitment and retention: nursing research among low-income pregnant women.

PMID- 9274069
TI  - Writing a useful literature review for a quantitative research project.

PMID- 9274070
TI  - Current research initiatives of AONE.

PMID- 9274071
TI  - The Nursing Management Minimum Data Set.

PMID- 9274072
TI  - Observations on dentistry (stomatology) the new China way.

PMID- 9274073
TI  - Composite morphology of the bone and associated support-tissue interfaces to
      osseointegrated dental implants: TEM and HVEM analyses.
AB  - Correlated transmission electron and high-voltage electron microscopic analyses
      examined the undecalcified bone and associated support tissues of 60 endosseous
      titanium blade and titanium and ceramic root-form implants in dogs. The implants
      supported fixed partial dentures for up to 2 years. Data obtained from this
      investigation suggest that a range of tissues, both mineralized and
      unmineralized, support osseointegrated dental implants. This study examined the
      tissues apposing not just isolated aspects of the implant surface, but the entire
      length of the implant, and found that mineralized and unmineralized tissues
      existed concurrently. Much of the implant surface was apposed by mandibular bone,
      and both root-form and blade implants osseointegrated. The densely mineralized
      collagen fibril matrix was often separated from the implant by only a 20-nm to 50
      nm electron-dense, ruthenium-positive deposit. High-voltage electron microscope
      stereology demonstrated that cellular processes extended directly to the implant
      from underlying osteocytes. In the same implants, areas containing an
      unmineralized collagen matrix interposed between the bone and implant surface
      were observed. In this region osteoblasts interacted with this matrix, and
      Howship's lacunae, containing vascular elements and osteoclasts, were also
      observed. The remodeling activities appear to be a homeostasis of catabolic
      activity (osteoclasts) and metabolic activity (osteoblasts). The apex of the
      implant was often apposed by a fibrofatty stroma. The support tissue response
      appears to be the result of the interrelations of osteoblasts, osteocytes, and
      osteoclasts in association with vascular elements. Therefore, the support tissue
      response to osseointegrated implants is a dynamic activity that involves the
      healthy interaction of these cells and tissues along the entire length of the
      implant.

PMID- 9274074
TI  - One-step surgical placement of Branemark implants: a prospective multicenter
      clinical study.
AB  - This prospective longitudinal multicenter study evaluated the clinical outcomes
      after placement and restoration of one-step Branemark implants into the maxillae
      and mandibles of completely and partially edentulous patients. Six surgical
      treatment centers participated in this study, in which 135 implants were placed
      into 63 adult patients. All implants were stable after placement. The majority of
      implants were placed into type B bone with minimal jaw resorption and type 2 bone
      quality. After implant placement, standard transmucosal healing abutments were
      firmly placed. The average amount of time between implant placement and
      prosthetic abutment connection was 170 days in the maxillae and 147 days in the
      mandibles. To evaluate crestal bone changes caused by implant placement, a
      periodontal probe was used to measure midbuccally from the top of the implant
      cylinder to the alveolar crest; in 29 patients, 54 midbuccal bone crest sites
      were remeasured following prosthetic abutment connection. Crestal bone changes in
      mandibles and maxillae were statistically and clinically insignificant. Six
      implants were lost prior to loading and one implant has not been restored. No
      implants or restorations were lost after loading. At 1 year, the implant success
      rate was 95.6%. Mesiodistal radiographic measurements from 34 patients were
      averaged, and changes from prosthetic abutment connection to, on average, 12
      months follow-up were compared. The radiographs, which were digitalized, measured
      from the bottom of the implant cylinder to the most coronal bone in contact with
      implant thread. For mandibular implants, the mean radiographic bone level at
      prosthetic abutment connection was 1.07 mm; after loading, it was 1.35 mm. For
      maxillary implants, the mean radiographic bone height at prosthetic abutment
      connection was 1.16 mm; after loading, it was 1.36 mm. These changes were not
      statistically significant. The 1-year outcomes from this patient series indicate
      that one-step Branemark implants provide excellent clinical results when placed
      in patients with good bone quality and quantity.

PMID- 9274075
TI  - Endosseous implant placement in conjunction with inferior alveolar nerve
      transposition: an evaluation of neurosensory disturbance.
AB  - This retrospective study evaluated neurosensory dysfunction and the implant
      success rate associated with 64 implants placed in 15 patients following
      transposition of the inferior alveolar nerve. A total of 21 inferior alveolar
      nerve mobilization surgeries were performed. The mean postoperative follow-up
      time was 41.3 months, with a range of 10 to 67 months. The effects of surgical
      technique and implant surface geometry on neurosensory dysfunction were evaluated
      by using light touch, brush stroke direction, and two-point discrimination. The
      implant success rate was 93.8% (60/64). The surgical technique that involved
      detaching the mental foramen resulted in a significantly greater incidence of
      neurosensory disturbance (77.8%, 7/9) than did the technique that left the bony
      foramen intact (33.3%, 4/12). The overall incidence of neurosensory disturbance
      was 52.4% (11/21).

PMID- 9274076
TI  - Cell and matrix reactions at titanium implants in surgically prepared rat tibiae.
AB  - The tissue response of rat tibiae to the surgical placement of commercially pure
      titanium implants was examined at 2, 6, 10, and 28 days. The transcortical
      placement of 1.5-mm x 2-mm implants resulted in the apposition of threaded
      implant surfaces within cortical and cancellous regions of the tibia. In all
      regions, evidence of bone formation was obtained through pre-embedding fracture
      of the implant from the bone tissue interface. Scanning electron microscopy
      examination of early responses revealed a fibrin clot and rapid formation of a
      loosely organized collagenous matrix. Many extravasated blood cells contacted the
      implant surface. At day 6, a more organized matrix containing many blood vessels
      opposed the implant surfaces, and few extravasated blood cells remained in
      contact with the implant surface. By day 10, the surgical wound was filled with
      woven bone that approximated the contours of the threaded implant. Later, few
      cells were attached to the retrieved implants. The consolidation of the forming
      matrix was clearly evident at 28 days. The tissue interface was an amorphous
      matrix that revealed the surface characteristics of the machined implant. Light
      microscopic analysis of ground sections indicated that, from day 6 onward, cells
      morphologically consistent with the osteoblastic phenotype were predominant
      within the gap between the surgical margin and implant surface. Osteoblastic
      cells had achieved the formation of an osteoid seam upon which bone formation
      progressed. The matrix that had formed represented woven bone containing many
      osteocytes. At day 6, evidence of remodeling was observed at sites distant from
      the surgical site, and by day 28 osteoclastic activity was observed at trabecular
      sites adjacent to the implant surface. The rat tibia model provides evidence of
      rapid formation of bone at implant surfaces.

PMID- 9274077
TI  - A 1-year follow-up of implants of differing surface roughness placed in rabbit
      bone.
AB  - Screw-shaped implants were prepared with three different surface topographies:
      One was left as machined, ie, a turned surface, and two were blasted surfaces
      with differing degrees of surface roughness. The surface topography was measured
      with a confocal laser scanning profilometer and the surface roughness was
      characterized using height and spatial descriptive parameters. The turned surface
      had an average surface roughness of 0.96 micron and an average peak spacing of
      8.6 microns. The two blasted surfaces had surface roughness values of 1.16
      microns and 1.94 microns, respectively; the corresponding values for the peak
      spacing parameter were 10.00 microns and 13.22 microns, respectively. After 1
      year in rabbit bone, the bone response to the turned implants was compared with
      the response to the two blasted implant surfaces. Firmer bone fixation was found
      for the two blasted surfaces, with statistically significant increases in removal
      torque and percentage of bone-to-metal contact. Furthermore, about 2 mm from the
      implant surface, the titanium release was similar for the turned and the 25
      micron aluminum oxide-blasted implants.

PMID- 9274078
TI  - Ten-year results for Branemark implants immediately loaded with fixed prostheses
      at implant placement.
AB  - This investigation was initiated to develop a method to provide patients with a
      fixed provisional prosthesis placed at the time of implant placement. Sixty-three
      standard 3.75-mm Nobel Biocare implants of varying lengths were placed into
      mandibular sites in 10 patients and followed for up to 10 years. Twenty-eight
      implants were immediately loaded at implant placement, providing support for
      fixed provisional prostheses, while 35 adjacent implants were allowed to heal
      submerged and stress-free. Following a 3-month healing period, the submerged
      implants were exposed and definitive reconstruction was accomplished. All 10
      prostheses supported by 28 implants placed into immediate function at the time of
      implant placement were successful during the 3-month healing period. Of these 28
      implants placed into immediate function, 4 ultimately failed. Of the 35 submerged
      implants, all are osseointegrated and in function to date. Life-table analysis
      demonstrates an overall 10-year survival rate of 93.4% for all implants. The 10
      year life-table analysis of survival is 84.7% for immediately loaded implants and
      100% for submerged implants. Statistical analysis of the submerged versus
      immediately loaded implants demonstrates failure rates for immediately loaded
      implants to be significantly higher (P = .022 by the log rank test). These data
      demonstrate that although mandibular implants can be successfully placed into
      immediate function in the short term to support fixed provisional prostheses,
      long-term prognosis is guarded for those implants placed into immediate function
      distal to the incisor region.

PMID- 9274079
TI  - A qualitative and quantitative method for evaluating implant success: a 5-year
      retrospective analysis of the Branemark implant.
AB  - A proposed protocol and differentiated success criteria for long-term evaluation
      of oral implants are presented. The protocol and criteria were applied to a
      retrospective patient material treated during a 1-year period and followed for 5
      years. The protocol comprised a two-stage analysis of the collected clinical
      data. First, a quantitative analysis of the outcome was made using a life table.
      Based on the information obtained during the follow-up, each implant was
      categorized into one of three groups: unaccounted for, failure, or survival. A
      qualitative analysis of the survival group was then performed by active testing
      against defined criteria. Depending on the modes of clinical and radiographic
      examinations and their results, surviving implants were either further assigned
      to one of three success grades or remained in the survival group. The data are
      presented in a four-field table at one level of success. Strict success criteria
      together with individual stability testing and radiographic examination of each
      consecutive implant should be used when a new implant system is evaluated or when
      a new application is explored. Radiography alone and more moderate success
      criteria may be used to document routine treatments, provided that an already
      well-documented implant system is studied.

PMID- 9274080
TI  - Psychosocial effects of implant-retained overdentures.
AB  - The aim of this study was to compare implant-retained mandibular overdentures and
      two conventional treatments for their effects on functional ability (chewing,
      speaking, etc), patient satisfaction, and quality of life (psychosocial
      functioning). Assignment of 90 patients was executed by means of a balancing
      allocation computer program to ensure the pretreatment comparability of the three
      groups. Twelve months after treatment, the average scores for almost all specific
      quality-of-life measures had improved significantly in all three groups. On
      average, all patients experienced fewer restrictions in their social activities
      and had fewer psychological problems because of their full dentures. No impact on
      the general quality of life was established. One year after treatment, all three
      dental treatment modalities had a comparably positive effect on dental health
      related quality of life.

PMID- 9274081
TI  - Implant rehabilitation of irradiated jaws: a preliminary report.
AB  - Ten patients (3 maxilla, 7 mandible), who had been treated for a head and neck
      malignancy by undergoing radiotherapy, had 42 implants (10 maxillary, 32
      mandibular) placed into the irradiated sites and either an overdenture or a fixed
      prosthesis fabricated. Of the 10 implants placed in the maxilla, 6 were lost;
      however, there was a 100% survival rate of the implants placed in the mandible
      (mean duration = 33 months). The use of longer implants and pre- or postimplant
      hyperbaric oxygen may be necessary in maxillary situations.

PMID- 9274082
TI  - Microbial leakage and marginal fit of the implant-abutment interface.
AB  - Two-stage implant systems result in gaps and cavities between implant and
      abutment that can act as a trap for bacteria and thus possibly cause inflammatory
      reactions in the peri-implant soft tissues. These gaps between the components are
      inevitable, and their clinical significance has so far been mostly neglected by
      both manufacturers and clinicians. The aim of the study was to determine whether
      there is microbial leakage at the implant-abutment interface. Thirteen different
      implant-abutment combinations were subjected to an in vitro experiment, in which
      the penetration of bacteria (Escherichia coli) was observed for 10 assemblies of
      each type. All implant systems presented microbial leakage. When the Frialit-2
      implant was supplied with a silicon washer, there were fewer cases of leakage.
      The width of the marginal gap between the prefabricated components, measured with
      a scanning electron microscope, was less than 10 microns in all systems.

PMID- 9274083
TI  - A comparison of radiographic bone height and probing attachment level
      measurements adjacent to porous-coated dental implants in humans.
AB  - The changes in crestal bone height observed in standardized radiographs of porous
      coated dental implants after 3 to 4 years of function in the support of
      mandibular overdentures is reported for a group of 48 completely edentulous
      patients. Possible correlations between bone height and each of probing
      attachment level, Plaque Index, and Sulcular Bleeding Index were investigated.
      Mean bone loss values were determined to be 0.43 mm in year 1, decreasing to 0.17
      mm and 0.13 mm in years 2 and 3, respectively. During year 4, there was an
      apparent mean gain of 0.05 mm. While the mean mucosal tissue thickness (1.3 mm)
      was similar to that reported by other investigators, it was not possible to show
      a correlation between bone height and probing attachment level. Likewise,
      correlations between bone height and Plaque Index or between bone height and
      Sulcular Bleeding Index could not be demonstrated.

PMID- 9274084
TI  - Effects of irradiation on osseointegration before and after implant placement: a
      report of three cases.
AB  - Three patients irradiated as a part of cancer treatment, both before and after
      placement of endosseous implants, were studied. Total irradiation doses varied
      from 80 to 195 Gy in the tumor/implant area. Implants failed at a rate of 64.2%
      during a 3-year follow-up period. All patients developed osteoradionecrosis in
      the tumor cavities adjacent to the implants. The combined effects of the pre- and
      postoperative irradiation, in conjunction with the placement of implants, appear
      to challenge the limits of osseointegration. Until further knowledge is obtained
      regarding how such highly radiated tissue should be handled, it is recommended
      that if anchorage of craniofacial prostheses is attempted according to
      osseointegration principles, it should be performed with the utmost care.

PMID- 9274085
TI  - Dental implants following radical oral cancer surgery and adjuvant radiotherapy.
AB  - Following radical oral cancer surgery and postoperative adjuvant radiotherapy
      with a total dose of 60 Gy, 71 IMZ and 150 Branemark implants were placed in the
      mandibles and 28 Branemark implants were placed in the maxillas of 60 patients
      between 1985 and 1995. Adjunctive hyperbaric oxygen therapy was not used.
      Osteoradionecrosis of the mandible occurred in two patients (3.4%), and necrosis
      of soft tissue in the floor of the mouth region occurred in three patients
      (5.2%). Twenty-one implants (18 in the mandible and 2 in the maxilla) were not
      osseointegrated when surgically exposed. In subsequent follow-up, 17 mandibular
      implants and 5 maxillary implants lost their osseointegration. The life table
      method indicated that 5-year actuarial implant success rates in the irradiated
      mandible were 77.5% for the IMZ system and 83.6% for the Branemark system. These
      differences were not statistically significant. Retrospective analysis indicated
      that the success of implants in the irradiated mandible is determined after an
      interval of 18 to 24 months. For a small number of Branemark implants in the
      irradiated maxilla, an actuarial success rate of 85.5% was found.

PMID- 9274088
TI  - Off-loading neuropathic wounds associated with diabetes using an ankle-foot
      orthosis.
AB  - Patients with chronic diabetes have a broad spectrum of associated peripheral
      neurologic deficits that culminate in an increased susceptibility to ulcer
      formation. The authors focus on the use of the ankle-foot orthosis as both a
      treatment and a definitive solution for achieving ulcer closure and for
      minimizing the chance of ulcer recurrence in the ambulatory patient. An analysis
      of the pathologic forces encountered, and the solution achieved with the ankle
      foot orthosis is presented. In addition, the results from a clinical pilot study
      in subjects with recalcitrant ulcers secondary to Charcot's neuroarthropathy are
      presented.

PMID- 9274086
TI  - Hemorrhage in the floor of the mouth during implant placement in the edentulous
      mandible: a case report.
AB  - This report describes a life-threatening hemorrhage in the floor of a patient's
      mouth during routine implant placement in the anterior mandible. Airway
      obstruction caused by hematoma development resulted in acute nasotracheal
      intubation and subsequent surgical intervention. Surgical, radiographic, and
      anatomic considerations to prevent severe bleeding are discussed. An extraoral
      submental approach in cases with large sublingual hematomas is recommended. An
      outpatient should be treated in or close to a hospital where these complications
      can be dealt with promptly and effectively.

PMID- 9274089
TI  - Current methods of measuring ulcers. A review.
AB  - Following a critique of the literature concerning two-dimensional and three
      dimensional measurement of ulcers, the authors describe an interrater and
      intrarater reliability study on linear measurement of an ulcer. Analysis of the
      results infers that neither method is reliable.

PMID- 9274090
TI  - Therapeutic footwear helps protect the diabetic foot.
AB  - There is evidence to indicate that therapeutic footwear can help prevent lower
      extremity amputation in patients with diabetes. The primary means of preventing
      amputation is to protect the insensitive foot from unnoticed trauma and excessive
      plantar pressures that occur during walking. The specific prescription of the
      shoe will depend on many foot risk criteria, but particularly on the patient's
      level of sensation, history of ulceration, and the amount of foot deformity. This
      article describes the type of footwear recommended for each of these increasing
      levels of foot risk categories.

PMID- 9274091
TI  - Factors associated with pedal ulceration in patients with diabetes mellitus.
AB  - Understanding the factors associated with pedal ulceration in patients with
      diabetes mellitus will increase the successful management of the high-risk
      diabetic foot and decrease the occurrence of ulcerative events. The authors
      review the associative factors that have been shown to be involved with pedal
      ulceration.

PMID- 9274092
TI  - Management of painful diabetic neuropathy. A treatment algorithm.
AB  - Peripheral neuropathy manifests as a painful syndrome in a significant number of
      individuals suffering from diabetes mellitus. Painful diabetic neuropathy may
      interfere with sleep, work, and activities of daily living. Patients and
      practitioners alike often view this challenging disorder as incurable. A broad
      spectrum of therapeutic alternatives and physiologic approaches to this complex
      clinical problem are available. Careful assessment and a rational approach based
      on the nature and location of pain will lead to success. The authors review the
      etiology, clinical presentation, and diagnosis of diabetic peripheral neuropathy.
      Available therapeutic alternatives are emphasized and an original treatment
      algorithm is presented.

PMID- 9274093
TI  - Imaging of digital neuromas.
AB  - In this case presentation, an incision was made on the nonweightbearing surface
      of the hallux directly over the mass in question, just long enough to allow for
      the isolation of the entire mass. This permitted easier identification of the
      mass and enabled dissection of the abnormal tissue and excision of only the tumor
      with a minimum of tissue trauma. Healing was uneventful and expedient largely
      because of the reduced tissue handling. Prior to the advent of magnetic resonance
      imaging, this type of preoperative detailed surgical mapping would not have been
      possible. Continuing improvements in magnetic resonance imaging hold great and
      increasing promise.

PMID- 9274094
TI  - Sickle cell myonecrosis involving the plantar musculature.

PMID- 9274095
TI  - Angioleiomyoma of the lower extremity.
AB  - Angioleiomyomas are benign soft tissue lesions that should be included in the
      differential diagnosis of any pedal soft tissue mass. There should be an
      increased index of suspicion for angioleiomyoma, especially when a freely movable
      subcutaneous mass is encountered in a middle-aged female patient. Treatment of
      such masses should involve surgical excision to relieve the symptomatology and to
      obtain tissue for a definitive histologic analysis. If the mass recurs, then the
      possibility of leiomyosarcoma should be explored.

PMID- 9274096
TI  - Treatment of venous ulcers with human skin equivalent.
AB  - In the author's clinical experience in rating venous ulcers, human skin
      equivalent has been efficacious, safe, cost-effective, and easy to use. This
      innovation is likely to become an important therapeutic tool for podiatric
      physicians who treat venous ulcers. Leg ulcers are a large economic burden to
      society, both in direct and total costs, including patient time lost from work
      for labor- and time-intensive therapies. The cost-containing measures of the
      managed care environment encourage treatment of venous ulcers in an outpatient
      center. Because human skin equivalent can be applied in such a setting, podiatric
      physicians will be able to treat venous ulcers routinely without referring
      patients to more costly settings such as hospitals or surgical centers. Because
      human skin equivalent is an effective alternative to standard venous ulcer
      therapies, this agent, which is currently under review by the Food and Drug
      Administration, should provide a viable treatment that may reduce the total costs
      associated with venous ulcer care.

PMID- 9274097
TI  - Gout and hypothyroidism.
AB  - A case of gout in a patient with primary hypothyroidism has been presented. Often
      missed as a companion of gout, hypothyroidism has a frequency of occurrence with
      gout that is significant and is probably a precipitating factor in these gouty
      attacks. The physician should be alert for signs and symptoms of this often
      occult disease in patients with hyperuricemia and gout.

PMID- 9274125
TI  - The state of the preoperative diagnosis of breast cancer today.

PMID- 9274126
TI  - Breast cancer epidemiology and risk factors.
AB  - Breast cancer is the most common malignancy among women in the Western society.
      Over the past decades it has become apparent that breast cancer incidence rates
      are increasing steadily, whereas the mortality rates for breast cancer have
      remained relatively constant. Information through the media on this rising number
      of cases has increased breast health awareness but has also introduced anxiety in
      the female population. This combination of factors has made the need for
      prevention of breast cancer an urgent matter. Breast cancer does not seem to be a
      single disease entity. A specific etiologic factor may therefore have more
      influence on one form of breast cancer than another. So far though, as shown in
      our summary of current knowledge on established and dubious risk factors, no risk
      factors have been identified that can explain a major part of the incidence.
      Efforts to identify other ways for primary prevention have also been
      discouraging, even though breast cancer is one of the most investigated tumours
      world-wide. Thus, at this point in time, the most important strategy to reduce
      breast cancer mortality is early detection through individual counselling and
      organised breast screening programs. The recent isolation of breast cancer
      susceptibility genes may introduce new ways to reduce the risk of breast cancer
      in a small subset of women.

PMID- 9274127
TI  - Molecular genetics of breast cancer.
AB  - In the last two decades, molecular studies have enlightened the complexity of the
      genetic alterations that occur in breast cancer cells. To date, more than 40
      different genes or loci have been found to be altered in breast carcinomas.
      Although some of these genes, as for example ERBB2, appear to be mutated in a
      high proportion of cases, their mechanism of action and their role in the
      different stages of cancer development are still poorly understood. More
      recently, two major determinants of the inherited predisposition to breast
      cancer, BRCA1 and BRCA2, have been isolated. As a consequence, it is now possible
      to screen families with a positive history of breast carcinomas for the
      identification of mutations carriers, in order to address these individuals into
      adequate programs of cancer surveillance and prevention.

PMID- 9274128
TI  - Diagnosis and prognosis of primary breast cancer.
AB  - The diagnosis of breast cancer should be made in the context of a
      multidisciplinary team: preoperative diagnosis can be made in over 90% of
      patients with symptomatic and screen-detected cancers. A preoperative diagnosis
      allows patients the opportunity to come to terms with the diagnosis of breast
      cancer and to consider their treatment options before progressing to therapeutic
      surgery. Surgery remains the primary therapeutic treatment for operable breast
      cancer with radiotherapy and systemic therapies as adjuvant treatments. Surgery
      in addition provides pathological specimens from which important prognostic
      information may be obtained. The traditional TNM classification in itself is no
      longer sufficient although there is still considerable prognostic information to
      be gained in staging patients. However, markers of tumour biology provide
      prognostic data independent of TNM staging. Both need to be considered in any
      overall assessment of patient prognosis.

PMID- 9274129
TI  - Breast cancer seeking agents: basic approach.
AB  - The knowledge of biochemical and physiological mechanisms involved in tissue
      localization is important so as to understand the information given by diagnostic
      nuclear medicine imaging, and eventually to design new radiopharmaceuticals. The
      cellular mechanisms which permit a high cancer uptake involve the perfusion and
      metabolism around the tumour tissue, the interference with normal function, the
      altered perfusion and/or metabolism within the tumour. All these phenomena can
      contribute to a high concentration of particular radiotracers in cancer and can
      create a favourable tumour/background ratio uptake sufficient for cancer imaging.
      Those molecules might be also powerful tools for reaching an advanced
      understanding of neoplastic and even "normal" cell biology. During these last
      years, some radiotracer specifically designed for different applications proved
      to be promising radiopharmaceuticals for breast cancer imaging. This is the case
      of monoclonal antibodies (Mabs) developed in the past against membrane cancer
      antigens. Other tracers, originally proposed for the study of vascular perfusion
      (cardiovascular tracers), have also revealed a capacity to be taken up by cancer
      cells. The radiopharmaceuticals mostly used as tumour seeking agents today
      (Radiothallium, Sestamibi, Tetrophosmin) were generated with other applications
      in mind. In this paper we review the mechanisms of uptake of the most relevant
      agents currently proposed for breast cancer imaging, including 18F
      fluorodeoxyglucose (FDG). The radiotracers will be examined on the basis of the
      available scientific evidence regarding their cellular uptake and release.
      Moreover, we report our preliminary studies on the cellular uptake and release of
      these and other compounds recently introduced in clinical trials.

PMID- 9274130
TI  - Scintimammography with 99mTc-MDP in the detection of primary breast cancer.
AB  - MATERIALS AND METHODS: The diagnostic accuracy of scintimammography with 99mTc
      MDP was evaluated in 400 consecutive women with clinical or mammographic
      suspicion of breast cancer, candidate to surgery and/or excisional biopsy.
      Lateral views of both glands were acquired, in prone position, 5-10 min after the
      injection of 550-740 MBq of 99mTc-MDP. The scintigraphic results were compared to
      mammograms and classified using the histological findings as gold standard.
      RESULTS: Mammography was suggestive for cancer in 231 (57%), suspicious in 49
      (12%) and indeterminate in 120 (31%) patients. Breast carcinoma was
      histologically proven in 330 women, benign breast diseases in 70. The tumor size
      ranged from 4 x 5 to 50 x 60 mm. 99mTc-MDP visualized as foci of increased uptake
      305/330 cancers (92%). In particular, in women with indeterminate mammograms the
      SMM had a diagnostic accuracy of 84%, correctly characterizing 101/120 lesions.
      Twenty missed cancers had largest diameter < or = 10 mm, 5 < or = 15 mm. Lack of
      99mTc-MDP uptake occurred in 64 out of 70 benign lesions. These lesions were
      classified as truly negative. Conversely, 3 fibroadenoma and 3 epithelial
      hyperplasia with moderate or severe atypia were falsely positive. The overall
      specificity was 91.5%; the accuracy was 92%, the positive and negative predictive
      values were respectively 98% and 72%. CONCLUSIONS: The results obtained in this
      study suggest that 99mTc-MDP scintimammography accurately detects breast
      carcinomas with largest diameter > 10 mm; it differentiates malignant from benign
      lesions, and it shows promising insights in characterizing breast abnormalities
      mammographically indeterminate.

PMID- 9274131
TI  - Scintimammography: the new role of technetium-99m Sestamibi imaging for the
      diagnosis of breast carcinoma.
AB  - Technetium-99-Sestamibi scintimammography has emerged as a new procedure for the
      imaging of breast tumors. Currently, a large clinical experience has been
      developed and the results published. At the present time, the major drawback of
      this procedure appears to be its low sensitivity for the detection of breast
      carcinomas smaller than 1 cm in diameter. There are other biologic and technical
      issues that remain to be overcome to optimally image the breasts. Some of these
      include: development of a dedicated breast imager using nuclear medicine
      techniques, development of stereotactic needle localization of the abnormalities
      that demonstrate focal increase uptake in women with normal mammogram and breast
      physical examination, manufacturing of a breast compression device so that we can
      immobilize the breast in place for more adequate imaging, overcoming the issue of
      unilateral or bilateral diffuse breast uptake that is noted in 7-10 percent of
      the cases and finally, determination of optimal dose and imaging factors. This
      review includes our experience at Harbor-University of California, Los Angeles
      Medical Center with the use of this agent for breast imaging since 1992.

PMID- 9274132
TI  - Diagnostic and prognostic role of 99mTc-Tetrofosmin in breast cancer.
AB  - 99mTc-Tetrofosmin (TF) is a lipophilic diphosphine compound routinely used for
      myocardial scintigraphy. Extracardiac utilization has occurred in evaluation of
      patients with malignant neoplasms and in parathyroid adenomas. Although its
      uptake mechanisms are not completely understood, they appear similar to those of
      99mTc Setamibi (MIBI). The importance of flow and the metabolic status of cells
      with an intracellular uptake depending on mitochondria and the Na+/K+ pump have
      been hypothesized. It has also been demonstrated that Tetrofosmin shares with
      MIBI the property of being a substrate for P-glycoprotein (P-gp), a multidrug
      resistance transporter. In this review the possible clinical role in breast
      cancer is analysed. First experiences suggest that scintimammography with TF is
      useful in patients with indeterminate Mammography and to obtain complementary
      data to avoid surgery and/or biopsy. TF is a reliable tracer for diagnosis of
      primary cancer, of local recurrence of axillary lymph node metastases.
      Preliminary data stimulate a possible role in functional imaging of
      chemoresistance and in differential diagnosis of distant metastases with main
      reference to the evaluation of single hot lesions at bone scan.

PMID- 9274133
TI  - Gamma probe guided sentinel node biopsy in breast cancer.
AB  - Axillary lymph node status is the most important pathological determinant of
      prognosis in early breast cancer. Determination of axillary status is crucial in
      clinical decision-making. It is currently accepted that the total axillary
      lymphadenectomy is the most reliable staging procedure. However, routine axillary
      dissection does not benefit a majority of early breast cancer patients who are
      node-negative, and the patients sustain the potential morbidity and the economic
      cost of this procedure. There is substantial evidence that there is an orderly
      progression of breast cancer metastases in a lymphatic basin, sentinel node being
      the first node to receive lymphatic drainage from the tumor site. Sentinel lymph
      node biopsy may prove to be the optimal sampling technique for staging of breast
      cancer patients. A large multicenter trial to study the clinical validity of
      sentinel lymph node biopsy in breast cancer is underway. This paper addresses the
      rationale for sentinel lymph node biopsy and discusses the technical issues with
      regard to anatomy and physiology of breast lymphatics.

PMID- 9274135
TI  - Expanded Programme on Immunization (EPI). Poliomyelitis eradication: the WHO
      Global Laboratory Network.

PMID- 9274134
TI  - The Children's Vaccine Initiative and the Global Programme for Vaccines and
      Immunization. Recommendations from the Special Advisory Group of Experts. Part 1.

PMID- 9274136
TI  - The Children's Vaccine Initiative and the Global Programme for Vaccines and
      Immunization. Recommendations from the Special Advisory Group of Experts. Part
      II.

PMID- 9274138
TI  - Our HMO view.

PMID- 9274137
TI  - Is patient care suffering?

PMID- 9274139
TI  - What's happened to the healing process?

PMID- 9274140
TI  - Video-assisted thoracoscopic surgery for management of spontaneous pneumothorax.
AB  - Spontaneous pneumothorax is a common problem facing thoracic surgeons, occurring
      in about nine individuals per 100,000 each year. Treatment options include
      observation, chest tube thoracostomy, and thoracotomy with or without
      pleurodesis. When surgery is indicated, thoracoscopic surgery has been shown to
      provide excellent results with low morbidity, low recurrence, high patient
      acceptance, a shorter hospital stay and possibly decreased costs. In this
      article, we present the successful treatment of two cases of recurrent
      pneumothorax via video-assisted thoracoscopic surgery, combined with mechanical
      and chemical pleurodesis.

PMID- 9274141
TI  - Curing children with leukemia in West Virginia.
AB  - Leukemia is the most common cancer in childhood with acute lymphoblastic leukemia
      (ALL) the most common subtype. While once uniformly fatal, today leukemia is a
      highly curable disease. To determine the outcomes of children with acute
      lymphoblastic leukemia in West Virginia, we performed a retrospective analysis of
      the results of treatment of children and adolescents with B-lineage ALL diagnosed
      between 2/86 and 1/91 and treated by the pediatric oncology teams at Morgantown
      or Charleston. Forty-one children with B-lineage ALL were identified and treated
      by a uniform protocol. Twenty-nine (71%) have remained disease-free for more than
      two years off therapy and are considered cured. Of the 10 patients who relapsed,
      five have now been off rescue therapy for greater than two years and are likely
      to be cured. Thirty-five of the original cohort of 41 children are alive and
      disease-free yielding an overall survival of 85%. The results of treatment of
      childhood leukemia in West Virginia are comparable to national data. Children
      with ALL diagnosed and treated by pediatric oncology teams in West Virginia have
      a very good chance of being cured.

PMID- 9274142
TI  - The dangers of jimson weed and its abuse by teenagers in the Kanawha Valley of
      West Virginia.
AB  - Jimson weed (Datura stramonium, a member of the Belladonna alkyloid family) is a
      plant growing naturally in West Virginia and has been used as a home remedy since
      colonial times. Due to its easy availability and strong anticholinergic
      properties, teens are using Jimson weed as a drug. Plant parts can be brewed as a
      tea or chewed, and seed pods, commonly known as "pods" or "thorn apples," can be
      eaten. Side effects from ingesting jimson weed include tachycardia, dry mouth,
      dilated pupils, blurred vision, hallucinations, confusion, combative behavior,
      and difficulty urinating. Severe toxicity has been associated with coma and
      seizures, although death is rare. Treatment consists of activated charcoal and
      gastric lavage. Esmolol or other beta-blocker may be indicated to reduce severe
      sinus tachycardia. Seizures, severe hypertension, severe hallucinations, and life
      threatening arrhythmias are indicators for the use of the anticholinesterase
      inhibitor, Physostigmine. This article reviews the cases of nine teenagers who
      were treated in hospitals in the Kanawha Valley after ingesting jimson weed. We
      hope this article will help alert primary care physicians about the abuse of
      jimson weed and inform health officials about the need to educate teens about the
      dangers of this plant.

PMID- 9274144
TI  - Influence of diet on the occurrence of intraepithelial microabscesses and foreign
      bodies in the ruminal mucosa of reindeer calves (Rangifer tarandus tarandus).
AB  - The forestomach mucosa was examined for pathological lesions in 12 healthy free
      ranging reindeer calves at different seasons, and in 32 reindeer calves fed
      lichen (n = 3), baled grass silage (n = 24) or pelleted feed (n = 5). No gross
      lesions were seen. Samples for histology were taken from reticulum, omasum and
      four sites in rumen. In histological sections a total of 182 intraepithelial
      microabscesses (IEMAs) and 16 foreign body lesions (FBLs) were observed in the
      ruminal mucosa, while 1 IEMA was found in omasum and no lesions in reticulum. The
      number of animals having 0, 1-10, 11-20 and > 20 IEMAs per four ruminal sections
      (one from each sample site) was 19, 19, 5 and 1, respectively. None of the free
      ranging or lichen-fed animals had more than 1 IEMA per four ruminal sections,
      while 58% (14/24) of the animals fed silage and 40% (2/5) of the animals fed
      pelleted feed had 2 or more IEMAs per 4 ruminal sections. FBLs occurred more
      frequently in animals with high numbers of IEMAs, and it is suggested that both
      IEMAs and FBLs are caused by plant particles penetrating the ruminal epithelium.
      The lesions did not seem to indicate an inferior diet nor influence the health of
      the animals.

PMID- 9274143
TI  - Well-differentiated papillary villoglandular adenocarcinoma of the uterine
      cervix.
AB  - This article presents a rare case of well-differentiated papillary villoglandular
      adenocarcima of the uterine cervix. This patient had vaginal bleeding and her
      disease was limited to the cervix. Since 1989, a total of 41 cases have been
      reported in the literature as a distinct entity. In the past, this tumor was
      included with other varieties of adenocarcinomas of the cervix and not as a
      separate entity. Due to its excellent prognosis, papillary villoglandular
      adenocarcinoma of the cervix, may be treated by a procedure less radical than a
      hysterectomy when the tumor is superficial with no vascular or lymphatic
      invasion. Recognition of this entity and separation from other varieties of
      adenocarcinomas of the uterine cervix are warranted.

PMID- 9274145
TI  - Fat/protein ratio in first DHI test milk as test for displaced abomasum in dairy
      cows.
AB  - First DHI test milk that was sampled prior to displaced abomasum (DA) diagnosis
      was used to evaluate milk fat/protein ratio (FPR) for prediction of subsequent DA
      in dairy cows. Odds ratio, sensitivity, specificity, predictive values, and
      likelihood ratio were determined. Twenty-seven DA cases were matched to three
      controls per case by herd and calving date. Milk was tested 18 to 23 days (95%
      CI) after calving, which was 9 to 17 days (95% CI) prior to DA diagnosis.
      Adjusted for parity and days in milk, a fat/protein ratio > or = 1.4 was 8.6
      times more likely (95% CI, 2.8 to 26) to come from a cow subsequently diagnosed
      with DA than a fat/protein ratio < 1.4. Using the cut off value of 1.4, the
      sensitivity of the FPR for DA was 80% and the specificity was 69%. A response
      operating characteristics curve indicated that the minimum sum of false negative
      and false positive results was at an FPR cut off value of 1.4. The likelihood
      ratio indicated that fat/protein ratios > or = 1.6 are 3.3 times more likely to
      come from cows that are diagnosed subsequently with DA than from cows without DA.
      The fat/protein ratio in first DHI test milk might be useful as a test for
      subsequent DA in dairy cows.

PMID- 9274146
TI  - Microbiology and pathology of fibrinous pericarditis in Danish slaughter pigs.
AB  - The prevalence of fibrinous pericarditis detected at slaughter in Danish
      slaughter pigs is approximately 0.02%. The microbiology and pathology of this
      disorder was studied through 46 field cases collected at slaughter from May 1994
      to August 1995. Mycoplasmas (Mycoplasma hyopneumoniae, M. hyosynoviae and M.
      hyorhinis) were isolated from the pericardium in 38 cases and from the joints in
      six. M. Hyopneumoniae dominated with 33 isolates from the pericardium.
      Actinobacillus pleuropneumoniae was isolated from the pericardium in three cases
      (as mono-infection in one and together with M. hyopneumoniae in two cases) and
      Actinomyces pyogenes was isolated from the pericardium twice (as mono-infection
      in one case and together with M. hyopneumoniae in another). A. pyogenes was also
      present in the lung, liver and kidney in one of these cases. Streptococcus suis
      was isolated together with mycoplasmas from the pericardium in three cases. The
      pericardium was sterile in three cases and contained a low grade mixed flora in
      two; the latter is believed to be a result of the slaughter procedure rather than
      an infection. No chlamydiae were found in connection with the microbiological
      examination. Parvovirus was found in one case in the pericardium and in two cases
      in the spleen. Forty-five cases were subacute to chronic. The gross pathological
      examination showed that bronchopneumonia, chronic pleuritis and synovitis or a
      low grade arthritis occurred in most cases. Only the arthritic lesions are
      believed to be pathogenetically concurrent with the pericarditis. Slight evidence
      of stasis of the liver and/or periangiolar edema was present in six cases. The
      histopathological examination confirmed the above mentioned findings. Bacterial
      colonies were found within the fibrinous layer on the pericardium in all cases
      from which either A. pleuropneumoniae, A. pyogenes or S. suis was isolated. It is
      concluded that in this study mycoplasmas, particularly M. Hyopneumoniae, are the
      more likely cause of fibrinous pericarditis in slaughter pigs.

PMID- 9274147
TI  - Effects of hypocalcaemia on blood flow to the ovaries of the sheep.
AB  - The objectives of the study were to use sheep as a model to determine whether a
      reduction in plasma calcium concentration similar to that observed during periods
      of postpartum subclinical hypocalcaemia in lactating dairy cattle might affect
      the blood flow to the ovaries. Different levels of hypocalcaemia were induced in
      each of six, non-pregnant sheep by the slow intravenous infusion of Na2-EDTA.
      Measurements of blood flow to the ovaries were made before and after the
      induction of hypocalcaemia, using 113Sn and 46Sc radiolabelled microspheres. As
      plasma ionized calcium was reduced, there was a significant decline in ovarian
      blood flow. Ovarian blood flow (percentage of resting) = 0.54 Ca++ (percentage of
      resting) + 58.4. This model was significant at P < 0.01, with R2 = 0.92.
      Accordingly, a reduction in plasma ionized calcium of 50% would yield a reduction
      in ovarian blood flow of 16%.

PMID- 9274148
TI  - Effect of weaning in the pig on ileal ion transport measured in vitro.
AB  - Early weaning in pigs results in small intestinal malabsorption and an increased
      susceptibility to E. coli infections. This is closely associated with villus
      shortening and crypt hyperplasia of the small intestine. The present study
      compared piglets either weaned at 3 weeks of age onto a high soya diet (n = 12)
      or an egg-based diet (n = 12) with piglets that remained on the sow (n = 12).
      Prior to weaning, care was taken to ensure that piglets only had access to sows
      milk. Serum anti-soya IgG was measured 7 days after weaning and sections of the
      mid-ileum excised and fixed for determination of crypt depth and villus height.
      Four pieces of 'stripped' mucosa were mounted in Ussing chambers in Krebs
      phosphate Ringer (with indomethacin) for determination of short circuit current
      (SCC) and unidirectional fluxes of Na22 and Cl36, half in mucosa-serosa (MS), and
      half in serosa-mucosa (SM) direction. After basal measurements of absorptive
      capacity of Na, supramaximal doses of prostaglandin E2 (PGE2) and theophylline
      were added to measure the intestinal secretory capacity for Cl. Anti-soya IgG was
      elevated in the group weaned onto soya when compared either with the group weaned
      onto egg or the unweaned group. All intestinal transport and histological
      parameters were similar in both the weaned groups, although some were different
      from the unweaned. The SCC (equal to Na absorption) and the villus height were
      reduced two-thirds by weaning, whereas crypt depth and Cl secretion were similar
      in all groups. It is suggested that weaning per se is causal for the observed
      changes in intestinal transport and morphology, but they are not influenced by
      whether the weaning diet is soya or egg based.

PMID- 9274149
TI  - Relationships between health and weight loss during lactation and between health
      and ability to return to oestrus after weaning in primiparous sows.
AB  - The study comprises observations in 301 Swedish Yorkshire primiparous sows
      belonging to a research herd. During the 6 weeks of lactation, they were fed
      according to a conventional feeding regime based on litter size. The sows were
      weighed at farrowing and at weaning. After weaning the sows were checked daily
      for standing reflex and blood samples for determination of plasma progesterone
      were drawn regularly. Diseases occurring during lactation were recorded in 223
      sows. A clinical health examination of these sows was also performed on the day
      of weaning, including body temperature, condition scoring, appetite, locomotor
      disorders, remarks on legs and mammary glands. A blood sample was drawn 1 week
      before weaning in 155 sows for analysis of blood haemoglobin concentration,
      packed cell volume, total white blood cell count, serum concentration of urea,
      creatinine, triglycerides, free fatty acids, total protein and electrophoretic
      separation of proteins. Sows with large weight loss had a higher total incidence
      of diseases during lactation, mastitis being the most common disease, than sows
      with small weight loss. Sows with large weight loss seemed to be more catabolic
      during late lactation than sows with small weight loss, according to the blood
      analyses. The blood analyses did not show any signs of subclinical infection
      being more common among sows with large weight loss than among sows with small
      weight loss. There were neither any significant differences in the total
      incidence of diseases during lactation nor in the health at weaning between sows
      returning to oestrus within 10 days of weaning and sows not returning within this
      time.

PMID- 9274150
TI  - Hereditary caprine phaeochromocytoma.
AB  - This report describes a hereditary caprine phaeochromocytoma in three
      generations. Besides conventional haematoxylin and eosin staining, potassium
      dichromate native staining method and transmission electron microscopy were
      performed.

PMID- 9274151
TI  - CNSs' future role in healthcare.

PMID- 9274152
TI  - Endotracheal reintubation: a closer look at a preventable condition.
AB  - We designed a prospective study of endotracheal intubations and reintubations in
      our inner city Level 1 Trauma Center, to determine the frequency and causes of
      reintubation and evaluate the impact of an educational intervention aimed at
      minimizing unplanned extubations (UEs). After an initial 3-month phase, efforts
      were instituted to educate healthcare providers to the causes of reintubation
      noted. An identical 3-month period was then studied to evaluate the efficacy of
      the interventions. There were 862 patients, all adults, in the initial phase of
      the study, with 40 reintubation events in 22 patients; of the 808 in the second
      phase, there were 16 reintubations in 13 patients. The reintubation rate
      decreased from 4.4% to 1.9% (p = 0.005). Reintubations after UEs decreased from
      14% to 5.2% (rate ratio, 0.374; 95% confidence interval = 0.141, 0.990). Multiple
      reintubation events decreased from 45% to 18.8% (p = 0.07). Increased provider
      education and protocol changes were associated with lower reintubation rates.

PMID- 9274153
TI  - Nutritional screening for the elderly: a CNS role.
AB  - Detection and treatment of nutritional disorders has surfaced as a major health
      concern for older persons. This article explores how one clinical nurse
      specialist (CNS) used advanced practice knowledge and skills to develop a
      nutritional screening program for an elderly population served by a nursing
      clinic. A study was conducted to determine the prevalence of risk factors for
      poor nutritional status in these elderly clients according to the Nutritional
      Screening Initiative. Eighty-two percent of the clients in the study presented
      with two or more risk factors for poor nutritional status. Therefore, a proposal
      was developed for a standardized screening and treatment program.

PMID- 9274154
TI  - Treatment of postprostatectomy urinary incontinence with behavioral methods.
AB  - Prostate cancer is the most commonly diagnosed cancer in men. The radical
      prostatectomy is the treatment of choice for localized cancer; however, this
      surgery carries with it the potential complication of urinary incontinence
      postoperatively. The increasing number of radical prostatectomies each year will
      thus lead to a growing number of patients suffering from postprostatectomy
      urinary incontinence. According to the medical literature, the treatment of
      postprostatectomy incontinence is almost always limited to pharmacological or
      surgical therapy. Because of the failure of the standard treatment options, many
      men are left to live with their incontinence. The guidelines for the treatment of
      urinary incontinence recommend the use of behavioral methods as first-line
      treatment for stress and urge incontinence. The potential treatment of
      postprostatectomy incontinence with the use of behavioral methods has a promising
      future for the advanced practice nurse and for the men who are affected.

PMID- 9274155
TI  - Where, oh where are we going?

PMID- 9274156
TI  - Two graduating master's students struggle to find meaning.
AB  - This article was initiated to help two graduating Master's students learn what
      might be expected of them upon graduation. The purpose of this article is to
      provide insight from reviewing the current literature on clinical nurse
      specialist's (CNS's) characteristics. The authors believe that this information
      is especially useful for graduate CNS students and helpful for those who
      currently hold CNS positions. Based on a literature review, the article
      categorizes descriptions of the characteristics of the CNS role as perceived by
      the CNS, management, staff nurses, and physicians. Within the identified
      perceptions of each group were the following similarly common CNS role
      components: (a) clinical practice, (b) education, (c) administration, (d)
      research, and (e) consultation. The key to congruent expectations and
      understanding of the CNS role is clear communication between the members of each
      group. Without this communication, the common result is ambiguity, conflict, and
      frustration.

PMID- 9274157
TI  - A curriculum vitae that gives you a competitive edge.
AB  - All nurses with advancing careers should maintain a current curriculum vitae (CV)
      to chronicle professional accomplishments. Whatever the work setting, a CV can
      showcase skills and achievements. It is used when applying for a new position,
      but also within one's current situation to inform other professionals of specific
      interests and abilities. This article reviews nursing literature regarding
      preparation of a CV and suggests a format for the advanced practice nurse to use
      when writing a CV.

PMID- 9274158
TI  - A community nursing center: a cost-effective approach to alternative therapies?

PMID- 9274159
TI  - A blending of health strategies in a community-based nursing center.
AB  - In today's changing healthcare climate, there is a need for a paradigm shift from
      a goal-driven model of care to a resource-driven model of care. This proposal
      describes a nursing center model that attempts to create a framework involving
      the community in determining the priority of its healthcare needs. Although it is
      desirable to offer all services to all people, it is apparent that costs will
      play a major role in determining service availability. Participation, support,
      and cost-effective outcomes are likely to be greater if residents of the
      community are involved in the services and programs provided. The advanced
      practice nurse (APN) is well suited to assist communities in determining
      priorities and meeting health needs in a cost-effective manner. The proposal
      submitted is based on a theoretical foundation that articulates a nursing
      framework and includes specific examples of services provided. It is flexible and
      can be adapted to any community. Modern scientific care, alternative therapies,
      education, and programs specific to the community's needs are also discussed. The
      presentation offers a nursing care delivery model in the community and discusses
      phases of implementation that have been initiated.

PMID- 9274160
TI  - Mental health, mental illness, and old age.

PMID- 9274161
TI  - The psychopharmacologic treatment of depression in elders.
AB  - Elders are at risk for depression from a variety of causes. Declining physical
      health or medical condition, loss of friends and family, adjustment to
      retirement, medication interactions or side effects, or a major depressive
      episode are possible causes of depression. The antidepressants available include
      TCAs, MAOIs, SSRIs, and the newer atypical medications. The selection of the
      appropriate drug for the particular person should be based on prior successful
      treatment with the medication, family history, medical conditions, and other
      medications. Side effects may be dose-related and must be closely monitored; they
      can be unpleasant and dangerous. "Start low and go slow" is the best practice for
      dosing antidepressants in elders. Nursing concerns include assessing and
      monitoring physical, emotional, and social changes, and patient and family
      education.

PMID- 9274162
TI  - Management of acute delirium in hospitalized elderly: a process improvement
      project.
AB  - This article will describe a systematic practical approach that was developed to
      evaluate and manage one of the most dangerous and costly geriatric emergencies in
      our nation-delirium in hospitalized frail elders. The article is about nurses and
      physicians who worked together in a continuous quality improvement process to
      find a collaborative method to reduce the occurrence, severity, duration, and
      devastating outcomes of acute delirium.

PMID- 9274163
TI  - Nursing care of the resident with Creutzfeldt-Jakob disease.
AB  - This article encompasses care of the resident and family and dealing with the
      staff's concerns regarding this rare, infectious dementia. Comparison is made
      between Alzheimer's disease and Creutzfeldt-Jakob disease, the symptoms and
      causative agent, precautions that need to be followed, nursing care and
      medications used in maintaining the resident's comfort, and the maximum quality
      of life possible during the course of this terminal disease.

PMID- 9274164
TI  - A walking program for wanderers: volunteer training and development of an evening
      walker's group.
AB  - In this article, the author describes an innovative program for wandering. A
      walker's group was developed in response to the explicit but nonverbal message
      from persons with dementia about their need for physical activity. The group was
      initiated in a nursing home, with volunteers to implement the program under the
      direction of clinical staff. The article details the volunteer orientation
      program and specific methods of implementation. The walker's group has been
      active for more than 4 years and is considered a valuable resource for managing
      residents who wander during the early evening hours.

PMID- 9274165
TI  - Identifying skilled management and evaluation needs of home health care patients.
AB  - This article describes the development of an assessment inventory to identify
      home care clients needing skilled management and evaluation services. Evidence
      supporting the inventory's content, criterion-related and predictive validity is
      presented. The inventory accurately predicted those patients readmitted within 60
      days of discharge. Home health care nurses found the inventory easy to use
      without being time consuming. Use of the inventory by home health care nurses
      will permit care agencies to more easily document the need to continue care and
      reduce recidivism and cost while increasing care quality.

PMID- 9274166
TI  - Mary Harper: nurse/politician extraordinaire. Interview by Patricia Ebersole.

PMID- 9274167
TI  - Managing mental illness at home--Part II: Clinical guidelines for psychiatric
      home health nurses.

PMID- 9274168
TI  - Keeping up with new developments in antidepressants.

PMID- 9274169
TI  - Ready-to-eat meals.

PMID- 9274170
TI  - Interventions used by staff nurses to manage "difficult" patients.
AB  - Interventions utilized by nurses to manage "difficult" patients and outcomes
      indicating successful interventions were investigated. Themes included getting
      the difficult patient label, difficult patient behaviors, reflecting on the label
      and passing it on, coping with a difficult patient, interventions that worked,
      and interventions that did not work. Clues indicating that patient behavior was
      changing were also identified.

PMID- 9274171
TI  - Achieving patient satisfaction: resolving patient complaints.
AB  - Patients demand to be active participants on and partners with the health care
      team to design their care regimen. Patients bring unique perceptions and
      expectations and use these to evaluate service quality and satisfaction. If
      customer satisfaction is not achieved and a patient complaint results, staff must
      have the skills to respond and launch a service recovery program. Service
      recovery, when done with style and panache, can retain loyal customers. Achieving
      patient satisfaction and resolving patient complaints require commitment from top
      leadership and commitment from providers to dedicate the time to understand their
      patients' needs.

PMID- 9274172
TI  - Too familiar for words: considering unaccounted-for aspects of nurse's work.
AB  - When things are too close to us, we have trouble seeing them clearly. Such may be
      the case with aspects of nursing work that are too familiar for words. The
      article reports a small case study from a qualitative study asking nurses to
      discuss work that no one else sees. Nurses use words such as facilitating, making
      it happen, filling in gaps, and putting the self in the situation to describe
      this work. With further study, these descriptions may offer insight into how
      nurses intervene to personalize the patient's experience with the health care
      system.

PMID- 9274173
TI  - Wisdom and falsehoods: naming the practice wisdom of nursing in the home and the
      falsehoods opposing that practice.
AB  - The article reviews qualitative studies of historical and contemporary home
      visiting by nurses to articulate the expert practice wisdom integral to this
      practice. Ten assumptions about reality that have become barriers to funding for
      home visits are examined, and strategies to challenge these false assumptions are
      proposed.

PMID- 9274174
TI  - Support systems of nurses recovering from chemical dependency: a pilot study.
AB  - Chemical dependency among nurses is a complex professional and ethical dilemma
      confronting the nursing profession. The article reports a descriptive study
      conducted to identify the support systems perceived to be supportive to nurses
      recovering from chemical dependency. Attitudes, beliefs, and identified support
      systems were examined using the Norbeck Social Support Questionnaire, the Miller
      Recovering Nurse Self-Report Questionnaire, and the Miller Targeted Sociogram.
      Recovering registered nurses identified counselors/ therapists and friends as
      most supportive during recovery. Conversely, family members/relatives were
      perceived as least supportive by recovering nurses.

PMID- 9274175
TI  - Exploration of the relationship between caring and cost.
AB  - Cost and caring are both dimensions of holistic nursing practice. Each is a term
      that is complex and ambiguous yet assumed to be simple and well understood.
      Nurses need to examine the specific embedded assumptions of cost and caring;
      measure each; and demonstrate their inter-relationship and effects on patient
      outcomes. Integral to caring is "professional vigilance," which cannot be
      delegated; attempts to do so may incur future hidden costs. Nurses are urged to
      be alert to cost-shifting that affects caring and quality. Advocacy for cost
      effective caring practices is urged through participation in governance
      structures.

PMID- 9274176
TI  - The family's experience of vigilance: challenges for nursing.
AB  - The article reports a qualitative study examining vigilance, or the close,
      protective involvement of families who stay with their hospitalized relatives.
      Participants described the meanings, patterns, and day-to-day experience of
      vigilance through five categories of meaning: commitment to care, emotional
      upheaval, dynamic nexus, transition, and resilience. These categories of meaning
      sensitize nurses to the family's experience of vigilance and have significant
      implications for nursing practice.

PMID- 9274177
TI  - The case of Mr. Martinez: ethical conflicts in home care.
AB  - Mr. Martinez recently was accepted into the Valley Hospice Program with a
      diagnosis of end-stage lung cancer. He currently lives with his daughter, Amelia,
      after moving from Puerto Rico 2 years ago after his wife died. His two sons and
      another daughter live within 20 minutes of Amelia's home. They are a close-knit
      family, and the children are committed to honoring Martinez' wishes to die in his
      room in Amelia's home.

PMID- 9274179
TI  - Home medical equipment suppliers: a critical home care partner. Interview by
      Sarah F Zarbock.
AB  - As the home care market continues to expand, opportunities and responsibilities
      associated with the delivery of care also will increase. One player in this
      changing landscape may be overlooked because greater attention seems to be paid
      to the concerns of physicians, hospitals, managed care companies, and community
      providers, such as visiting nurse associations and pharmacies. These often
      "silent partners" are the companies that provide home medical equipment (HME) and
      services and that play a critical role in enabling patients to be cared for at
      home.

PMID- 9274178
TI  - Suicide myths and health care provider bias.
AB  - If most health care providers believe suicide is not an acceptable alternative
      for clients to alleviate their anguish, then why are these providers not more
      diligent in assessing clients for suicidal ideation (thoughts about suicide)? One
      reason is providers believe the myths associated with suicide, which can prevent
      them from becoming involved with elderly clients who are suicidal.

PMID- 9274180
TI  - Scabies: an itchy problem.
AB  - Scabies-a small word that can, and often does, impart great anxiety and
      apprehension among health care workers (HCWs). Yet the epidemiology associated
      with this human parasitic infestation is well understood, as are the mechanisms
      for both its treatment and control.

PMID- 9274181
TI  - Is my antihistamine safe?
AB  - The Food and Drug Administration (FDA) has announced its intention to withdraw
      the approval of terfenadine (Seldane), terfenadine with pseudoephedrine (Seldane
      D), and generic versions of terfenadine. Before granting approval for the
      marketing of fexofenadine (Allegra), terfenadine's active metabolite, the FDA
      determined terfenadine's benefits outweight its risks, despite its, known
      potential for serious cardiac effects.

PMID- 9274182
TI  - What is this condition? Elbow bursitis.

PMID- 9274183
TI  - Resources for care & security. An update on tax-free viatical settlements.

PMID- 9274184
TI  - Implementing continuous quality improvement in home care: a success story.
AB  - Continuous quality improvement (COI) is fast becoming the method of choice for
      home care organizations to assess and improve the quality of their services. This
      article illustrates care agency took the first step toward implementing COI.
      Interviews with the executive director, clinical director, continuous quality
      improvement coordinator, business office manager, and health information manager
      provide a glimpse into their initial concerns and their successes. Advice from
      each participant is offered to agencies attempting to implement COI for the first
      time.

PMID- 9274185
TI  - Home health nurses: stress, self-esteem, social intimacy, and job satisfaction.
AB  - A survey of 253 home health care nurses' perceptions of work-related stress, self
      esteem, social intimacy, and job satisfaction found that stress has a negative
      correlation with self-esteem, social intimacy, and job satisfaction. A positive
      correlation, however, was found between self-esteem and social intimacy and job
      satisfaction. Health system administrators, owners, and directors had
      significantly higher levels of self-esteem, nurses with 5 years or more in their
      home health nursing position had significantly higher levels of self-esteem. The
      survey found that nurses with less than a baccalaureate degree possessed
      significantly lower levels of sociability than those with a graduate or
      baccalaureate degree. Administrators and managers scored significantly higher on
      sociability than head nurses.

PMID- 9274186
TI  - Restless leg syndrome.

PMID- 9274187
TI  - American Subacute Care Association. Outcomes-based home health care improves
      results for patients with CHF.

PMID- 9274188
TI  - Joint Commission on Accreditation of Healthcare Organizations. What to expect
      during your Joint Commission survey.

PMID- 9274189
TI  - Partnerships?

PMID- 9274190
TI  - Nursing across cultures: the South Asian client.

PMID- 9274191
TI  - Proposed revisions to Medicare conditions of participation.

PMID- 9274192
TI  - Solving the puzzle of negative behavior in elderly home care patients.

PMID- 9274193
TI  - Hans.

PMID- 9274194
TI  - Agency-university collaboration: home care early in the student curriculum.
AB  - Changes in the healthcare system mandate community-focused experiences for
      nursing students. This article describes the collaboration of San Jose State
      University School of Nursing faculty and the education coordinators of two home
      health agencies in developing successful home health clinical experiences for
      students early in the curriculum. Questions and concerns of agency staff
      strategies for developing home health experiences between home health agencies
      and nursing faculty are presented.

PMID- 9274195
TI  - A dressing technique to stabilize percutaneous tubes.

PMID- 9274196
TI  - One agency's formula.
AB  - Specialty teams are said to be an innovative solution for providing the
      coordinated, cost-effective care sought by managed care companies. This article
      describes one home health agency's systematic process for development of disease
      management and specialized skills teams.

PMID- 9274197
TI  - Practical research: an effective tool in home healthcare.

PMID- 9274198
TI  - Medicare coverage issues.

PMID- 9274199
TI  - Reflections on home care.

PMID- 9274201
TI  - [How to search the Internet and ... find things].

PMID- 9274200
TI  - Buyouts for nurses. A simple accounting entry, or an irremediable loss of
      expertise?

PMID- 9274202
TI  - [AIDS: a world, a desire].

PMID- 9274203
TI  - [Between euthanasia and therapeutic stubbornness: the ethics of discussion].

PMID- 9274204
TI  - [Profile: Antoinette Gimenes-Lambert--15 years of fight against AIDS. Interview
      by Sylvie Valliere].

PMID- 9274205
TI  - [Offering a hand to new parents: listening or informing?].
AB  - Nurses working in the perinatal field have a variety of objectives, one of which
      is helping new parents feel competent in their new role. Recognizing parents'
      potential and offering them the support they need to realize it is one of the
      strategies suggested by the Department of Health and Social Services (MSSS, 1991
      and 1992a). In order to identify aspects of nursing interventions at the time of
      the post-natal visit that promote parental skills, the authors conducted research
      into the concept of empowerment. Following an in-depth survey of the literature
      on this concept, they came up with a definition of interventions promoting
      empowerment, and used this definition as the basis for their analysis of
      perinatal nurse-client relations. The study, subsidized by the Fondation de
      recherche en sciences infirmieres du Quebec (FRESIQ), was carried out between
      1993 and 1995 in four CLSCs in the Eastern Townships region. Thirteen nurses
      agreed to record their conversations with first-time parents during 20 postnatal
      visits.

PMID- 9274206
TI  - [Family participation--what does the psychiatric patient think of this?].

PMID- 9274207
TI  - [To reinforce the link between research and practice--a doctorate in nursing
      science].

PMID- 9274208
TI  - Contemporary nursing practice.

PMID- 9274209
TI  - Health policy and the nursing profession: a deafening silence.
AB  - The Australian healthcare system, and those of many other Western countries are
      experiencing significant shifts in the development of health policy. Many of
      these shifts are directly related to economic factors that have contributed to
      the spiralling costs of health care. The trends in health policy appear to be
      embracing a 'market driven' approach to the distribution of resources and health
      services. Technology and medical developments have contributed to these current
      economic trends. Over the past 20 years nurses have been faced with significant
      shifts in the direction of health policy to the extent that many policies have
      significantly impacted upon their practice without their apparent contribution.
      Several theoretical positions exist about nurses' lack of policy participation.
      This paper examines some of the current health policy changes in Australia that
      are perceived to have had the greatest impact on the nursing practice, and
      identifies some of the barriers to the nursing profession's participation in the
      formulation of health policy.

PMID- 9274210
TI  - The interview that wins the job.
AB  - Obtaining a nursing position is often the first challenge for the graduate nurse.
      Understanding the interview process and making a plan that will ensure the
      graduate is placed in the best possible light is important for success in the
      interview process. This paper discusses getting ready for the interview, setting
      up the interview, dressing for the interview, the actual interview and following
      up the interview. Adherence to these guidelines can facilitate the graduate's
      success in obtaining the desired position.

PMID- 9274211
TI  - Factors associated with back pain in nursing staff: a survey in Athens, Greece.
AB  - Factors associated with self-reported back pain were investigated using
      questionnaire data on 407 female nurses from a large hospital in Athens, Greece.
      Factor analysis was used to construct indices of pain and its impact on normal
      life, and also to summarize work load descriptions. Pain factors were examined in
      relation to work load and personal characteristics by logistic regression.
      Statistically significant items, in relation both to pain and impact, were the
      existence of previous back injury, self-reported headaches and the 'carrying and
      lifting' factor of work load which principally included moving equipment. Age,
      height and weight were not associated with back pain. Compared to a similar study
      by Harber and colleagues in California, United States of America, the factors
      associated with back pain were quite similar in this study even though the
      prevalence of back pain was much higher among Greek nurses and their work load
      was physically much more demanding.

PMID- 9274212
TI  - Quality of life: perceptions of residential care.
AB  - Residents in selected aged care facilities in Australia (n = 185) and New Zealand
      (n = 44) completed a 56 item quality of life instrument derived and refined
      through grounded theory. Ten scales were developed from the items. Analysis of
      variance (ANOVA) indicated that there were no main differences as a function of
      cohort (Alzheimer's or non-Alzheimer's) or country of residence (Australia or New
      Zealand). Significant differences emerged as a function of the source of help in
      completing the instrument. Where nursing staff assisted residents complete the
      instrument, scoring indicated that residents enjoyed a better quality of life
      than if the instrument was completed by the resident alone, or with assistance
      from non-nursing staff and others, including relatives, welfare students and
      diversional therapists. Nursing staff rather than non-professional nursing staff
      tended to work more with non-Alzheimer residents when completing the
      questionnaire. Significant differences were also discovered in the ranking of
      concerns on the basis of cohort and country of residence.

PMID- 9274213
TI  - Humour as experienced by patients and nurses in aged nursing in Finland.
AB  - Humour is an integral part of everyday life and therefore a component of the care
      and treatment of elderly patients in the modern health care. This article deals
      with the role of humour in aged nursing from the perspective of the nursing home
      residents. It also describes some preliminary results of our study on the meaning
      of humour to professional nurses. The chief motivation for the study is to
      provide a deeper understanding of humour as a part of aged nursing and as a
      'phenomenon', which should also help us in the continuing challenge to improve
      the quality of nursing care. In this study the qualitative approach was used
      because the focus of interest was on an issue that has received only little
      attention in earlier research. The research material consists of data from
      patients and nurses. The data were collected via interviews and essay-type
      responses. The data obtained were analysed using the qualitative method of
      content analysis. In the light of our findings here, humour can be described as a
      joie de vivre which manifests itself in human interaction in the form of fun,
      jocularity and laughter. The assumption is supported by earlier research results
      which indicated that humour is an individual and personal matter and, in aged
      nursing care it is also very much a context-bound phenomenon. Humour makes it
      easier for some of the elderly patients to experience a positive, human
      relationship with the nurse. According to the results it seems to us that
      research should be continued and intensified into the role and use of humour in
      elderly people's everyday life and particularly in gerontological nursing care.

PMID- 9274214
TI  - In uncharted waters: confronting the culture of silence in a residential care
      institution.
AB  - This paper describes a study grounded in feminism, which explored the experiences
      of three registered nurses who were employed in a residential care institution in
      which they believed the standard of care to be unacceptably poor. Ultimately, the
      nurses became 'whistle blowers'. Data surrounding these events were gathered
      through serial encounters and analysed using feminist interpretive methods. Three
      distinct phases were revealed: (i) trepidation and optimizm; (ii) barriers and
      obstacles; and (iii) disillusionment and defeat. It was in this final phase that
      the whistle blowing occurred. For these women, whistle blowing was an
      intervention of last resort; a stressful and negative event that carried personal
      and professional cost. Issues pertaining to professional autonomy and patient
      advocacy are raised, together with concerns surrounding the appropriation by
      business people of the language and images of nursing, and the power of these
      people to negatively impact upon nursing practice.

PMID- 9274215
TI  - Evaluation of a programme to train Russian emigre nurses.
AB  - This project evaluates a curriculum model designed to specifically help Russian
      emigre nurses overcome major barriers to employment in the United States of
      America. Training cycles included: vocational English, basic nursing skills,
      socialization theory, transcultural care theory, clinical preceptorships, job
      search workshops and NCLEX-RN preparation. Specific learning objectives and
      outcome criteria were developed, evaluated and adapted for subsequent training
      cycles based on pilot programme testing.

PMID- 9274216
TI  - A conjoint appointment involving a nursing research management role.
AB  - Nursing conjoint appointments have taken a number of different forms and included
      various hospital roles such as ward manager, educator and consultant. This paper
      discusses an appointment trialed at a lecturer/middle manager level with a
      functional hospital role of Assistant Director of Nursing (research). The
      hospital role included activities categorized as: research consultations;
      research proposal reviews; committee membership; and research project
      involvement. The academic activities included a half-time teaching load, student
      clinical placement supervision and thesis/treatise student supervision. The
      development and implementation of the position, including background, role
      structure, appointment conditions and work practices are discussed. Issues that
      were highlighted during the 2 year trial included: the teaching load compared to
      reimbursement funding; the actual activities involved in the position; the level
      of appointment required to be most effective in the role; and concomitant
      university study by the appointee.

PMID- 9274217
TI  - Nursing and researching.
AB  - An example from an interpretive phenomenological study of the experience of
      chronic illness in rural Australia is used to describe aspects of the nursing
      researcher relationship with study participants and to draw some comparisons
      between this relationship and the nurse and client relationship. Nurses are bound
      to serve their clients; however, the researcher's principal purpose is to come to
      know and understand. These different principal purposes do not necessarily mean
      that the two relationships are completely different processes. There is a case
      for making the most of some overlapping skills and to see the results as positive
      'by-products'. The question as to whether, or to what extent it is possible for
      the researcher to help participants intentionally is an issue worthy of
      discussion.

PMID- 9274218
TI  - 'Because that's the way we've done it!' A review of circuit handling within an
      anaesthetic department.

PMID- 9274219
TI  - Haematology and palliative care: an account of shared care for a patient
      undergoing bone marrow transplantation for chronic myeloid leukaemia.

PMID- 9274221
TI  - Oxygen protocols for the prevention of hypoxemia. A review for case managers.
AB  - Case managers are challenged by the need to ensure quality care for patients in
      the face of increasing demands on the health care system to provide more economic
      care. These economic pressures often cause hospitalized patients to be
      transferred from critical care areas earlier than in years past. As a result,
      hypoxemia-inadequate oxygenation of the blood-is emerging as a serious patient
      safety problem in noncritical care areas of the hospital. The medical literature
      recently has begun to document hypoxemia in some patient groups on the general
      care floor, where continuous monitoring of patients' respiratory status usually
      is no longer employed. The serious health consequences of hypoxemia, the fact
      that it can affect nearly any hospitalized patient, and the potentially high cost
      of treating hypoxemia-related morbidity are drawing the attention of the medical
      community. Case managers are in a position to address this emerging problem by
      working with hospitals and health care institutions to identify at-risk patients
      and develop strategies to improve both clinical and financial outcomes. Patient
      care protocols are one effective strategy to standardize monitoring of patients
      deemed to be at risk. Early detection and treatment of hypoxemia have the
      potential to improve patient care while significantly reducing medical costs.

PMID- 9274222
TI  - Medicaid, Medicare, and managed care. Case management for dually eligible
      clients.
AB  - A dually eligible person is one who qualifies for both Medicaid and Medicare
      benefits. When elderly persons need acute care services, they enter a different
      part of the service delivery system where Medicare is the major payer. Typically,
      this part of the system is disconnected from the long-term care portion. Rather
      than working together for the maximum benefit of consumers, each part of the
      system is motivated to guard its resources jealously. Integration of Medicare and
      Medicaid offers states the opportunity to demonstrate how better care can be
      provided by using resources more effectively. However, managed care may bring
      changes in care delivery and new payers for services which may affect the role of
      case managers.

PMID- 9274223
TI  - Personal assistance services and case management.
AB  - Case managers can serve a vital role in the coordination and support of consumer
      driven personal assistance services (PAS) for people with disabilities. Personal
      assistants provide services such as assistance with mobility needs, transferring
      in and out of a bed or wheelchair, bathing, dressing, grooming, toileting,
      preparing meals, check writing, and communication interpretation. Maximum
      independence and autonomy are often achieved when disabled people manage the
      services that they need. By focusing case management on doing what the individual
      directs, the case manager can enhance independence, autonomy, and accommodation.
      In response to needs identified by its members, the Paralyzed Veterans of America
      (PVA) began to develop a comprehensive PAS training program for institutions,
      agencies, families, and individuals. The Independent Living Training Program is
      based on an approach to PAS that incorporates a case management model that
      supports the principles of consumer empowerment and self-determination.

PMID- 9274224
TI  - Client-centered case management. A survey of state programs.
AB  - With funding from the Administration on Aging, the National Resource Center:
      Diversity and Long-Term Care surveyed state administrators of programs serving
      elders in 24 states in 1994. This survey sought to document what written
      guidelines and training case managers receive in promoting client autonomy in
      care planning. In discussions with respondents and review of written materials
      provided by the states, surveyors explored whether clients received written
      information about services, the structure for seeking client input into care
      planning, and the structure for soliciting client feedback once the care plan was
      in place. Of the states included in this survey, few have developed and
      implemented guidelines or provide case managers training to promote client
      autonomy in the care-planning process. After reviewing the survey findings, the
      authors make two policy recommendations for states to consider in this area.

PMID- 9274225
TI  - Cash and counseling demonstration and evaluation. Start-up activities.
AB  - One possible approach for making long-term-care systems more consumer-directed is
      to provide the consumer with a cash alternative. Advocates have touted the
      possible advantages of this approach, while nay-sayers have worried about the
      potential for abuse and questioned the claims of cost savings. This article
      describes the Cash and Counseling Project, a large-scale demonstration project
      with a rigorous, policy-driven evaluation built into it. Written prior to the
      project's actual implementation, this article specifically reviews the major
      evaluation questions, and the state selection process.

PMID- 9274226
TI  - Empathy: a literature review and concept analysis.
AB  - Empathy appears to be an important concept in the interpersonal repertoire of the
      nurse. There are a number of definitions and models of empathy available in the
      literature. These definitions and models are explored and analysed using Walker &
      Avant's (1983) approach to concept analysis. A model case of the concept is
      described and the relevant defining attributes identified. A borderline case and
      an example of 'not the case' are also examined. This concept analysis may assist
      practitioners to develop the behavioural skills of empathy and to recognize and
      coach it in their students and colleagues.

PMID- 9274227
TI  - Research and the configuration of nursing services.
AB  - This paper is concerned with the way in which nursing research has influenced
      changes in the organization of nursing services, particularly the shift from so
      called traditional nursing to new nursing. To this end published research and
      professional literature are selectively reviewed. The case is made to support the
      view that change in nursing has been driven forward by the evangelical zeal of
      opinion leaders rather than evidence. It is suggested that holistic care as
      embodied in new nursing is no longer affordable. Market pressures have
      precipitated a revisiting of the task basis of nursing. An effective anchor would
      have been a solid body of research evidence pointing up the value new nursing may
      have. Regrettably not enough research was done prior to the diffusion of new
      nursing. What was done was not always adequate, and what was adequate was not
      effectively deployed by nurse leaders. Nursing is the largest workforce in the
      NHS and has attracted a great deal of policy interest. It is suggested that it
      will become increasingly important for nursing to be more strategic, and develop
      its own professionally driven research agenda. The future of the nursing
      profession in uncertain. It is clear that evidence-based practice is centre
      stage, and there is a need for nursing to re-negotiate its professional
      boundaries and to develop intellectual partnerships in order to move the
      knowledge base of practice forward.

PMID- 9274228
TI  - 'Effective' Australian gerontology nurses: a repertory grid analysis.
AB  - Repertory grids were completed by gerontological nurses (N = 60) to elicit the
      personal constructs they used to characterize gerontological nurses, effective
      gerontological nurses and the extent to which participants believed themselves to
      be effective as nurses working in this specialist field. Analysis of pooled
      repertory grids indicated that the personal construct 'caring, compassionate,
      empathetic' was rated most highly as characteristic of gerontological nurses in
      general and of effective gerontological nurses. Cluster analysis of individual
      repertory grids showed no significant difference between self-perceptions of
      participants as effective gerontological nurses and the ideal gerontological
      nurses they would like to become. Other findings of this research indicate that a
      variety of aspects of gerontological nursing need improvement if negative
      perceptions of this area of nursing practice are to be altered.

PMID- 9274229
TI  - Nursing staff's perceptions and experiences of primary nursing practice in
      intensive care 4 years on.
AB  - This study explores the perceptions of staff who have been practising primary
      nursing for more than 4 years in intensive care. It considers what primary
      nursing is, what its benefits, disadvantages, and role impact are and other
      issues within an intensive care setting from the staff's perceptions and
      experiences. Although many of the perceived advantages and disadvantages are
      similar to experiences from other areas of nursing, there are some differences.
      The differences seem to relate to the way primary nursing is practised within the
      research setting-each primary nurse works with the same small team of associates,
      which is perceived as providing added benefits in terms of personal support and
      development of junior staff. The changes in role are seen to reflect other models
      in the literature which focus on becoming more patient centred and on working
      therapeutically. A number of future issues are addressed.

PMID- 9274230
TI  - Patient anxiety in the accident and emergency department.
AB  - Structured interviews were carried out with a sample of 96 patients to identify
      the sources of anxiety for patients in the accident and emergency (A & E)
      department. Only two patients reported that they were not at all anxious about
      any aspect of being in A & E. The average number of anxieties reported was 6.9.
      The most frequently reported anxieties were 'not being able to carry on your
      usual activities', 'not knowing what will happen to you in the department',
      'having to undergo an uncomfortable procedure', 'feeling pain' and 'not knowing
      what is wrong'. The findings indicate that patients were as concerned with
      psychological and social aspects associated with admission as they were about
      physical factors. The authors suggest that it is essential for nurses in A & E to
      assess patients holistically and consider their psychological state and social
      circumstances as well as their physical condition. There is also a need for
      closer links to be developed between accident and emergency departments and other
      community health agencies and for more emphasis to be placed on referral to other
      bodies.

PMID- 9274231
TI  - Increased parental participation in a paediatric surgical day-care unit.
AB  - Day care is currently a common way of providing treatment for minor and average
      paediatric surgical procedures. The purpose of this study was to assess possible
      benefits of increasing parental involvement in the care of operated children in a
      day-care surgery unit. By giving parents information and education about post
      operative care, the goal was to facilitate recovery and minimize time spent in
      hospital. Results show that parents in the intervention group were well prepared
      to assume a greater part of the care of their children. Children in the
      intervention group appeared to have less pain and fewer children vomited post
      operatively than children in the control group.

PMID- 9274232
TI  - Advocacy in nursing--perceptions of practising nurses.
AB  - This paper reports on a qualitative study which examined the interpretation of
      patient advocacy by practising nurses. Focus group interviews, which allowed
      respondents to recount and share their particular 'stories' of patient advocacy,
      were used to collect data. Results indicate that a triadic model of advocacy
      predominated which involved the nurse in a conflict/potential conflict situation.
      The patient's requests, the patient's fear, the patient's vulnerability or
      threats to the patient's human rights provoked an advocacy response in the
      perceptive nurse. The nurse was sustained in the role through patient
      recognition, the nurse-patient relationship, emotional strength, moral
      justification and knowledge/expertise legitimacy. The nurse used direct and
      indirect means to protect the patient against incompetent/inappropriate practice
      and/or represent patient/family choice, the advocacy activity resulting in
      positive or negative outcomes. In conclusion it is argued that if the triadic
      conflict model of advocacy outlined by this research is to be sustained by
      practising nurses, the potential risks involved should be recognized.
      Professionalization of the role may be the only way forward if the ethical code
      (United Kingdom Central Council, 1992) continues to make patient advocacy a
      mandatory activity for the professional nurse.

PMID- 9274233
TI  - Nutrition: a hard nut to crack. An exploration of the knowledge, attitudes and
      activities of qualified nurses in relation to nutritional nursing care.
AB  - Provision of adequate nutrition is recognized as essential, yet malnutrition
      continues to be reported in patients admitted to hospital. The effects of
      malnutrition in hospital patients have been well documented; however, most work
      relating to nutritional management has been produced by members of Nutrition
      Support Teams, nurse specialists and interested clinicians, whilst the majority
      of hospitals are still without such specialist posts. This study used two data
      collection methods to gain information about the attitudes, nutritional knowledge
      base and nutrition-related nursing care in a large trust hospital in the South of
      England. A survey of care plans for documentation of nutrition-related nursing
      activities, carried out on the day of discharge for all patients from five wards
      over a period of a fortnight (totalling 141 sets of documentation), was followed
      by a questionnaire to all qualified nurses on these and a further four wards (110
      nurses). Results demonstrated that nurses generally felt that nutritional
      assessment was primarily their responsibility. Whilst there was evidence of
      knowledgeable and proactive nursing care, it also appeared that there were fairly
      widespread deficiencies in the knowledge, communication and co-ordination
      required to ensure consistent good practice.

PMID- 9274235
TI  - Chinese elderly people's perceptions of nursing homes in Hong Kong.

PMID- 9274234
TI  - The nature of expert psychiatric nurse practice: a grounded theory study.
AB  - This study examines what psychiatric nurses regard as the nature of expert
      psychiatric nurse practice. The study focuses on the beliefs and principles of
      psychiatric nurses currently working within a psychiatric unit. Using grounded
      theory methodology, data were coded and analysed, producing an integrated
      framework of expert psychiatric nurse practice comprised of four core variables:
      'attitudes/philosophy', 'knowledge', 'skills' and 'roles'. It is suggested that
      the nature of expert psychiatric practice is an evolutionary concept and that as
      this practice develops the integrated theory presented will need to develop in
      parallel.

PMID- 9274236
TI  - A nurse practitioner-managed after-hours clinic for a Native American
      reservation.
AB  - The Indian Health Service implemented a plan for an after-hours clinic which has
      been providing services since May 1991 on the Wind River Indian Reservation in
      Wyoming. Integral to the plan for the after-hours clinic was the family nurse
      practitioner as primary care provider. The after-hours clinic expands the health
      care services of the clinic by 3 hours on weekdays and 8 hours on Sundays. The
      role of the nurse practitioner as a primary care provider was introduced to the
      Wind River Service Unit, along with an after-hours clinic operation. Since the
      inception of the after-hours clinic, behavioral health and dental services and a
      women's clinic have been added.

PMID- 9274237
TI  - Counseling the patient with chronic illness: strategies for the health care
      provider.
AB  - The process of assisting a patient with chronic illness starts with understanding
      chronicity from the patient's perspective and its effect on the health care
      relationship. By learning the impact that chronic illness has on the individual
      and recognizing the factors involved with adapting to chronic illness, the health
      care provider can hope to reach this understanding. An appreciation of the coping
      strategies commonly used by patients with chronic illnesses helps in selecting
      the appropriate counseling methods to foster psychological health. Specific
      strategies, such as reciprocal trust, Rational-Emotive Therapy, and the "School
      of Bravery" approach, and spiritual care are discussed.

PMID- 9274239
TI  - Calcium supplementation.
AB  - Calcium is necessary for the prevention and treatment of diseases such as
      osteoporosis, hypertension, and, possibly, colon cancer. Supplementation is
      useful when dietary calcium intake is low, as is the current situation in North
      America. There are many factors to consider before recommending any one form of
      supplement. A consideration for calcium carbonate tablets is whether the tablet
      disintegrates and whether or not a lack of food or acid in the stomach will
      hinder utilization. Other forms of calcium, particularly the chelated calcium
      salts, are better absorbed in fasting achlorhydric subjects but have less calcium
      per gram of supplement. Interaction of calcium with other mineral nutrients and
      the presence of contaminating metals has focused attention on safety. Based on
      present evidence, chelated calcium and refined calcium carbonate tablets
      (including those labeled as antacids) may be safely and effectively ingested by
      most people at doses generally recommended for treatment or prevention of
      osteoporosis. One should not exceed 2,000 mg of calcium, except at the advice of
      their health care provider, as inadvertent mineral deficiencies may arise.
      Persons at risk for developing milk-alkali syndrome, such as thiazide users and
      persons with renal failure, should be identified and monitored for alkalosis and
      hypercalcemia when using calcium supplements.

PMID- 9274238
TI  - Migraine headache.

PMID- 9274240
TI  - Unintended pregnancy. U.S. Public Health Service.

PMID- 9274241
TI  - Breast cancer among men: raising awareness for primary prevention.
AB  - The American Cancer Society estimated that in 1993 1,000 new cases of male breast
      cancer would be diagnosed in the United States and 300 men would die from the
      disease. The clinical picture of breast cancer among men resembles that seen in
      women, and the development of the disease among men has been attributed to
      similar hormonal and genetic causes. The mortality rate from breast cancer is
      also similar, when corrected for chronological age and stage of the disease at
      the time of diagnosis and treatment. Guidelines for patient education, health
      screening, and patient support are presented.

PMID- 9274242
TI  - Evaluation and management of plantar puncture wounds.

PMID- 9274243
TI  - Reference books for professional use of the information superhighway.

PMID- 9274244
TI  - Put prevention into practice. Violence. U.S. Public Health Service.

PMID- 9274245
TI  - Managing adolescent depression in a primary care setting.

PMID- 9274246
TI  - Professional autonomy: essential for nurse practitioner survival in the 21st
      century.
AB  - This article examines nurse practitioners' (NPs) professional autonomy as a
      critical component of future practice success and survival. Professional autonomy
      provides the basis for defining and negotiating NPs' work and worth in primary
      care. Outcome data and analyses that delineate the unique and overlapping
      practice roles and responsibilities of physicians and NPs will help determine the
      relative value of their work. Nurse practitioners practicing as physician
      "substitutes" risk professional survival. Nurse practitioners need to identify
      nursing as their practice paradigm and nurses as their professional identity.

PMID- 9274247
TI  - Clinical considerations of heparinization.

PMID- 9274248
TI  - Health care for travelers: Internet sites of interest.

PMID- 9274249
TI  - The carotid bruit in clinical practice.

PMID- 9274250
TI  - Gaucher's disease: diagnosis, treatment, and management.

PMID- 9274251
TI  - Managing polymyalgia rheumatica and giant cell arteritis in the primary care
      setting.

PMID- 9274252
TI  - Karen Ignani, CEO and President, American Association of Health Plans. Interview
      by Carole Jennings and Jan Towers.

PMID- 9274253
TI  - Advance directives: role of nurse practitioners.
AB  - Advance directives are documents that guide end of life decisions. Although
      advance directives are a fairly recent phenomenon in health care, they are
      grounded in both legal and ethical principles. Studies show few people have
      completed advance directives. Persons do not tend to complete advance directives
      for various reasons. Lack of knowledge has been identified, as well as belief
      that physicians should initiate the discussion and that the topic is appropriate
      only for the elderly or those in poor health. Many nurse practitioners practice
      in primary care settings, which are ideal for discussions about advance
      directives. Nurse practitioners possess the opportunities and skills to discuss
      advance directives with their patients.

PMID- 9274254
TI  - Smoking cessation for pregnant women and their partners: a pilot study.

PMID- 9274255
TI  - Identification and treatment of cytomegalovirus retinitis in patients with AIDS.

PMID- 9274256
TI  - Stroke: an unusual case presentation.

PMID- 9274257
TI  - Non-insulin-dependent diabetes mellitus.

PMID- 9274259
TI  - Epidermal-derived factors in the treatment of a chronic leg ulcer.

PMID- 9274260
TI  - Treatment of unhealed burns with severe complications.

PMID- 9274261
TI  - Use of a hydrocellular adhesive dressing in a terminally ill baby.

PMID- 9274262
TI  - Evaluation of a new polyurethane foam dressing.
AB  - The treatment of moderately to heavily exuding wounds requires a dressing that
      will remove excess exudate while ensuring optimum conditions at the wound site
      and preventing maceration of the surrounding skin tissue. This prospective,
      stratified, randomised clinical trial was designed to assess the performance and
      safety of a new polyurethane foam dressing compared with a hydrocellular
      dressing. Both dressings are currently available to community nurses for the
      treatment of these wound types. Sixty-one patients recruited to the trial. They
      were grouped according to wound type: 20 leg ulcers, 20 Grade 2 or Grade 3
      pressure sores and 21 other wounds that included traumatic, acute and chronic
      wounds and burns. Patients were randomized to treatment and dressing changes and
      assessments were undertaken as required. Condition of the wound and surrounding
      skin, comfort, ease of use and leakage from the dressing were monitored at each
      assessment. Treatment continued for six weeks or until the wound was lightly
      exuding (defined as absence of leakage with the dressing remaining in place for
      more than four days on two consecutive occasions). Photographs and tracings of
      the wounds were taken weekly. The results showed that the two dressings were
      similar in performance in that they could remain in place for approximately 2.5
      days, irrespective of wound type. There were no statistically significant
      differences in surrounding skin condition, reduction in wound size, patient
      comfort or ease of application and removal.

PMID- 9274263
TI  - The cytocompatibility of hydrocolloid dressings.
AB  - The purpose of this study was to evaluate the effect on fibroblast proliferation
      of hydrophilic particles isolated from six commercial hydrocolloid dressings. The
      hydrophobic adhesive matrix of six hydrocolloid dressings was removed using a
      reflux extraction method with an organic solvent (xylene). The remaining
      hydrophilic particles were dissolved in complete cell growth medium containing
      10% (v/v) foetal calf serum and added to confluent human dermal fibroblasts grown
      in monolayer in final concentrations of 0.1 and 0.01% (w/v). Control cells
      received growth medium alone. The fibroblasts were incubated with the hydrophilic
      particles and the thymidine analogue 5-bromo-2'-deoxyuridine (BrdU) for 24 hours.
      The incorporation of BrdU into DNA was used as a measure of cell proliferation
      and determined using an ELISA kit. The results were expressed in percentage of
      control-treated wells and analysed using analysis of variance. Apart from Comfeel
      Plus, the hydrophilic particles of hydrocolloid dressings significantly inhibited
      fibroblast proliferation at 0.1% compared to control-treated fibroblasts (p <
      0.05).

PMID- 9274264
TI  - Cellular communication and the action of growth factors during wound healing.

PMID- 9274265
TI  - Managing pressure relief in a special needs nursing scheme.
AB  - People admitted to the Royal Devon and Exeter Hospital, who require continued
      long term nursing care and fulfil at least one of seven identified criteria, can
      be referred to a special needs scheme for placement in a private local nursing
      home supported by education, free loan of electronic pressure-relieving equipment
      and visits to monitor progress. A clinical nurse specialist in tissue viability
      is also available for advice and the supply of equipment to any residents with
      tissue viability problems who are referred by nursing home staff. From a total of
      293 referrals during the first four years of this scheme, 155 patients have been
      supported in nursing homes through the scheme. At the time of placement, 71
      patients (46%) had pressure sores, all of whom received the free loan of an
      electronic mattress. A further 21 patients, whose skin integrity was at high
      risk, also received mattresses. The sores ranged from Grade 2 to Grade 4
      (Stirling grading scale). During the study period, only four patients placed
      under the scheme suffered deterioration in their sores (all immediately prior to
      death). Over the three years before the scheme began, 14 patients per year were
      admitted from private nursing homes to an acute hospital with a primary diagnosis
      of pressure sore. Since the introduction of the scheme this figure has been
      reduced to nil.

PMID- 9274266
TI  - Principles of closed surgical wound care.

PMID- 9274267
TI  - A home-care team in paediatric wound care.

PMID- 9274268
TI  - The selection and use of compression bandages.

PMID- 9274269
TI  - A team approach to pressure relief for people with disabilities.

PMID- 9274270
TI  - Prospective payment for rehabilitation and long-term care hospital payments.

PMID- 9274272
TI  - Keeping the focus on specialty nursing practice.

PMID- 9274273
TI  - To touch a patient.

PMID- 9274274
TI  - The treatment of rectovaginal and vesicovaginal fistulas in women with childbirth
      injuries in Ethiopia.

PMID- 9274275
TI  - Reflections of certified wound care nurse.

PMID- 9274276
TI  - Wet, dry, or damp?

PMID- 9274277
TI  - Presence of pressure ulcer prevention methods used among patients considered at
      risk versus those considered not at risk.
AB  - PURPOSE: This study examined pressure ulcer-prevention strategies available for
      patients considered at risk versus those considered not at risk. DESIGN: The
      study used a prospective, longitudinal design. SETTING AND SUBJECTS: Six hundred
      ninety-four patients from units of five acute care hospitals, a rehabilitation
      facility, and two nurses' home care caseloads participated in the investigation.
      INSTRUMENTS: Data-collection instruments included the Braden Scale for risk
      assessment, demographic information, and the Pressure Ulcer-Prevention Strategies
      tool, which assessed for the presence of 16 pressure ulcer-prevention strategies.
      METHODS: All patients admitted to a participating unit during a 2-month period
      were followed up until discharge. Depending on the site, patients were assessed
      for the presence of pressure ulcer-prevention strategies one to three times per
      week. RESULTS: Patients in the at-risk group versus those in the not-at-risk
      group were more likely (p < 0.01) to have the head of the bed in a low position,
      a pressure-reducing bed surface, pressure ulcer prevention charted, a positioning
      wedge, incontinence cleanser and ointment, heel protection, a prevention care
      plan, a trapeze, and a posted turning schedule. The at-risk group had
      significantly (p < 0.01) more prevention strategies present than did the not-at
      risk group. However, the percentage of patients placed on a pressure ulcer
      prevention program was low for both groups. CONCLUSIONS: Pressure ulcer
      prevention was evident for the at-risk group, but at a low rate. Institutions
      must continue to explore this critical area affecting patient outcomes.

PMID- 9274278
TI  - The path to a clinical pathway: collaborative care for the patient with an
      ostomy.
AB  - A colostomy and ileostomy clinical pathway was developed at a southeastern
      teaching hospital in 1990 in response to excessive lengths of stay and costs at
      our hospital compared with national data for this patient group. A
      multidisciplinary clinical pathway team was formed and charged with the
      development, implementation, and ongoing monitoring of the clinical pathway tool
      and its effect on the outcomes of the population of patients with colostomies and
      ileostomies. Through this multidisciplinary collaboration, length of stay and
      cost have been reduced while quality care indicators have been maintained. This
      article presents the sample pathway we developed and describes the pathway
      development process, documentation, the variance analysis process, and the
      outcomes achieved with implementation. A urostomy/urinary diversion pathway that
      was developed after variance analysis review of the colostomy and ileostomy
      clinical pathway is also presented.

PMID- 9274279
TI  - Improving the performance of small incontinence pads: a study of "wet comfort".
AB  - PURPOSE: The wet comfort of small, disposable incontinence pads has been found to
      correlate strongly with overall acceptability. This study examined the
      relationship between pad properties (absorption capacity, strike-through, and
      wetback) and wet comfort. DESIGN: A group of women with light incontinence were
      asked to report on the wet comfort of a series of experimental pads made up to
      the same design geometry but in different combinations of materials. METHODS:
      Three different pad variants were selected, and two experiments were conducted.
      Experiment 1 used a single-blind design in which 20 testers were supplied with a
      random mix of the three unlabeled pad variants. All pads were saved for weighing
      and scored for overall performance, wet comfort, and absorbency. In experiment 2,
      subjects used each pad variant in turn for 1 week and at the end of each week
      compared that pad with the one used the previous week. MAIN OUTCOME MEASURES:
      Absorption capacity, wetback, and strike-through properties for each pad variant
      were measured in the laboratory setting, and wet comfort was measured by a
      written tool completed by participants during clinical trials. RESULTS: Data
      analysis from experiment 1 revealed statistically significant differences among
      pad variants, particularly when assessed for absorbency. Differences for wet
      comfort were less marked and only achieved significance when those with ratings
      of good or OK for wet comfort were compared with those with a score of poor. In
      experiment 2, no statistically significant differences were found for wet
      comfort. CONCLUSIONS: Overall, the improvement in wet comfort achieved by a
      substantial increase in absorption capacity and reduction in wetback were
      disappointing. The relatively small sample and the design specifications of the
      pad may have masked differences. Cost considerations mean that more evidence is
      needed to justify the inclusion of more expensive materials and production stages
      in the manufacture of small pads.

PMID- 9274280
TI  - Patient satisfaction with a reusable undergarment for urinary incontinence.
AB  - PURPOSE: We investigated patient satisfaction with a reusable undergarment for
      urinary incontinence. SUBJECTS AND SETTING: One hundred seventy-five participants
      with reported urinary incontinence from two urology-based clinics at large
      teaching hospitals and one prostate cancer support group participated in the
      study. METHODOLOGY: Each participant was given a minimum of one reusable
      undergarment for urinary incontinence. Participants used the undergarment for an
      average of 10 days (range 1 to 60 days). During the trial period, subjects
      alternated the reusable undergarment with their previous urine-containment
      devices, usually disposable pads, while the undergarment was being washed.
      Patient satisfaction was evaluated with a questionnaire. PRIMARY OUTCOME
      MEASURES: Patient satisfaction with the reusable undergarment was measured for
      six categories: (1) physical comfort, (2) ability to keep skin dry, (3) ability
      to prevent wet spots, (4) discretion, (5) odor control, and (6) confidence when
      wearing the garment versus previously used containment devices. RESULTS: Of the
      175 subjects, 126 (33% female and 67% male) completed and returned the 7-page
      questionnaire. All respondents reported at least one urinary incontinent episode
      while wearing the reusable undergarment. Occurrence and degree of leakage by self
      report varied from light leakage (33%) to moderate leakage (48%) and heavy
      leakage (17%). Patient satisfaction was measured as follows: (1) 83% rated the
      overall comfort of the undergarment as very good or excellent; (2) 52% said they
      felt very dry or dry when wearing the product after an incontinent episodes; (3)
      75% rated the ability to prevent wet spots on outer clothing as adequate or
      excellent; (4) 75% rated the discretion of this product as excellent; (5) 80%
      rated the ability to control odor as adequate or excellent; and (6) 67% felt more
      confidence with this reusable undergarment than with other products with which
      they were familiar. CONCLUSION: The reusable garment provided effective
      containment from urine loss among this group of incontinent women and men.

PMID- 9274282
TI  - [Specifics in the care of severely ill premature infants--nursing report].

PMID- 9274281
TI  - Patient with dystrophic toenails, calluses, and heel fissures.
AB  - Options in Practice presents different management approaches to the same clinical
      situation. You are invited to submit a brief case description, including the
      specialty nursing care provided, and several glossy, color photographs of the
      clinical situation. The case material will then be sent to another wound, skin,
      ostomy, or continence care clinician, who will also address management concerns.
      Alternative solutions to difficult wound, skin, ostomy, or incontinence clinical
      situations will be published.

PMID- 9274283
TI  - [Perspectives and challenges for pediatric hospitals from the physician's
      viewpoint].

PMID- 9274284
TI  - [Child abuse and neglect. Epidemiology and diagnosis].

PMID- 9274286
TI  - [Suicide in children and adolescents].

PMID- 9274285
TI  - [Sexual abuse of children--a thematic review for pediatric nursing].

PMID- 9274288
TI  - [Importance for pediatrics of the quality of training in pediatric nursing].

PMID- 9274287
TI  - [Medicine between mother and child. 1. Separation of mother and child after birth
      -background, consequences and alternatives].

PMID- 9274289
TI  - [Toxic and less toxic plants. 33].

PMID- 9274290
TI  - [Memorandum for women or parents who lost their child during pregnancy or shortly
      after birth].

PMID- 9274291
TI  - [Insufficient participation of the population in summer meningoencephalitis
      vaccinations].

PMID- 9274292
TI  - [Skin disorders in newborns and infants caused by imperfect care].

PMID- 9274293
TI  - [Nursing standards--care of children after heart catheterization].

PMID- 9274294
TI  - [Care before and after heart catheterization].

PMID- 9274295
TI  - [Accidents in children--developmental-physiological and psychological aspects].

PMID- 9274296
TI  - [Integrated maternity nursing].

PMID- 9274299
TI  - [Toxic and less toxic plants. 34].

PMID- 9274297
TI  - [Reading and understanding reports on nursing research].

PMID- 9274298
TI  - [Physical therapy in children].

PMID- 9274300
TI  - [Open letter on the situation of home care and pediatric nursing].

PMID- 9274301
TI  - [Venous leg ulcer. 2. Symptoms, clinical aspects, therapy, documentation].

PMID- 9274302
TI  - [Skin neoplasms--early diagnosis and prevention].

PMID- 9274303
TI  - [Bronchial asthma--a new therapeutic concept].

PMID- 9274304
TI  - [What to do when the pressure is increasing? or: making use of comprehensive
      offers of aids for the increase of nursing quality].

PMID- 9274305
TI  - [Comrade, angel, Sister of Mercy ... the image of the nurse in the popular novel.
      2].

PMID- 9274306
TI  - [The situation of practical training on intensive care units. An attempt at
      clarification].

PMID- 9274307
TI  - [Flexible reaction to physical pain--WHO recommendations on therapy with various
      morphine preparations].

PMID- 9274308
TI  - [Physiological and psychological aspects of laughter].

PMID- 9274309
TI  - [A normal day of teaching? Joys and despair of a nursing school teacher].

PMID- 9274310
TI  - [Ambulatory therapy. An alternative for patients with cystic fibrosis].

PMID- 9274311
TI  - [Tracheobronchial aspiration during general anesthesia].

PMID- 9274312
TI  - [Venous leg ulcer. 1. Basis, differential diagnosis].

PMID- 9274313
TI  - [Economics and consistent decubitus prophylaxis--is it possible?].

PMID- 9274314
TI  - [The future of our hospital system. The background conditions of the third step
      in our health care reform].

PMID- 9274315
TI  - [Free welfare in Europe].

PMID- 9274316
TI  - [The inward journey, an approach to one's self and others].

PMID- 9274318
TI  - ["Turkish at the bed side?" What does it mean?].

PMID- 9274317
TI  - [Work as an addiction].

PMID- 9274319
TI  - [Friend, angel, sister of mercy ... the image of the nurse in popular novels].

PMID- 9274320
TI  - [Physician and chaplain in conversation. Medical knowledge and the physician's
      art. Jeremias Gotthelf born 200 years ago].

PMID- 9274321
TI  - [A successful nursing concept for patients with fecal incontinence. Personal
      attention instead of padding].

PMID- 9274323
TI  - [Hospital based home care in an identity crisis].

PMID- 9274322
TI  - [Missing fathers--missing examples].

PMID- 9274324
TI  - [When you are sick you belong to a different class of people].

PMID- 9274325
TI  - [The box lady. A short story].

PMID- 9274326
TI  - [We are counseling you. Sick leave is not family leave].

PMID- 9274327
TI  - [Thoughts on the interactions between nurse and patient. Politeness, a tool of
      the trade?].

PMID- 9274328
TI  - [Prevention and health promotion at the community level. Health is within
      everyone's reach].

PMID- 9274329
TI  - [Plea for our profession...].

PMID- 9274330
TI  - [Meetings of therapeutic health personnel: a time for privileged talk].

PMID- 9274331
TI  - [Reflexology: who, when, how?].

PMID- 9274333
TI  - [Suicide by the elderly. When the joy of living is lost].

PMID- 9274332
TI  - [An unforgettable journey].

PMID- 9274334
TI  - [Making the invisible visible. Development of the nursing potential].

PMID- 9274335
TI  - [Comprehensive information for parents of children in ambulatory treatment.
      Returning home with confidence].

PMID- 9274336
TI  - [Talks and thoughts at night].

PMID- 9274337
TI  - [Tarif contracts for independently working nurses].

PMID- 9274339
TI  - [Hello, vacation].

PMID- 9274338
TI  - [Another way to warrant adequate care. From navigation at sight to instrument
      navigation].

PMID- 9274340
TI  - [Things are moving at the nursing school. Two new programs of study].

PMID- 9274341
TI  - [An interdisciplinary treatment concept for patients with eating disorders. The
      rage to be thin].

PMID- 9274342
TI  - [Mobbing--even among nurses].

PMID- 9274343
TI  - [The vision of youth without drugs is unfortunately a dream].

PMID- 9274344
TI  - [Swiss Nursing Society--flexible and innovative on a safe basis].

PMID- 9274345
TI  - [The end of a battle].

PMID- 9274346
TI  - [Introduction of the information system "KIS". The computer as a helpful
      instrument in psychiatry].

PMID- 9274347
TI  - [Caring--a provable and indispensible part of nursing].

PMID- 9274349
TI  - [A communication tool that permits us to keep up hope: spirituality: the fourth
      dimension of care].

PMID- 9274350
TI  - [The stakes of the anti-drug policy. Utopia or reality: a choice for society].

PMID- 9274351
TI  - [Professionals fighting drugs. Nurses are involved at all levels].

PMID- 9274352
TI  - [Nursing care of drug addicts in prison. Sowing some grains of hope].

PMID- 9274354
TI  - [Psychiatry of the aged. An international consensus].

PMID- 9274355
TI  - [You don't have scabies, after all...].

PMID- 9274353
TI  - [Interview with a former addict. "With methadone I am comfortable in my skin".
      Interview by Francoise Taillens].

PMID- 9274356
TI  - Facing the start-up challenge again.

PMID- 9274357
TI  - Guilty as charged.

PMID- 9274359
TI  - The use of nurses in alternative dispute resolution.

PMID- 9274358
TI  - Verifying the authenticity of medical records.

PMID- 9274360
TI  - Role playing turns interviews into win-win situations.

PMID- 9274361
TI  - The nurse executive: walking on water or walking on dangerous ground?

PMID- 9274362
TI  - Consulting and the nursing process.

PMID- 9274363
TI  - Deposition abstracts provide insights into personal injury cases.

PMID- 9274365
TI  - Avoiding the "alphabet soup" syndrome.

PMID- 9274366
TI  - Applying assessment skills to analyzing medical-related cases.

PMID- 9274364
TI  - Tapping into the Internet--one LNC's experience.

PMID- 9274367
TI  - What's your customer satisfaction attitude?

PMID- 9274368
TI  - [A study of the process of change in cerebral disease patients' recognition of
      their particular disabilities: a grounded theory approach].
AB  - The purpose of this study was to describe how Cerebral Disease patients recognize
      their disabilities and what influences them. The data were analysed by using a
      grounded theory approach and were them compared with previous findings from stage
      theory. Eight individual patients were interviewed during their rehabilitation
      phase. The results are as follows: 1) The process of Cerebral Disease patients'
      recognition was not uniform in the same way as in the case of stage theory but
      was characterized by a three-type pattern of depression. 2) Each type of
      depression was found to improve after "Support imprinting experience". 3) Many
      patients suffered physical injuries through trying to achieve too much in too
      short a time. This was a means, however, for recognizing the extent of their
      capabilities.

PMID- 9274369
TI  - [Characteristics of the social support for pregnant women in Japan--according to
      concept of four kinds of social support].
AB  - The qualities of the social support and social network for pregnant women
      influence their mental and physical states during pregnancy and childcare period.
      We adopted Cronenwett's conceptual framework and the four kinds of the social
      support (emotional, material, information and comparison support) based on
      House's definition to examine the qualities of them. As for support resources,
      pregnant women's family, friend and husband's family provided most of the social
      support for pregnant women. Among of them, husband, mother, sisters, and
      husband's mother were especially important members, providing satisfactory
      support for pregnant women. The pregnant woman's and her husband's families were
      the main resources of emotional and material support. Friend was the that of
      information and comparison support. The pregnant women most perceived emotional
      support with the largest supportive members. Material support was perceived the
      most clear and independent kind from other three ones of supports.

PMID- 9274370
TI  - [Components of decision-making among hemodialysis patients].
AB  - The purpose of this descriptive study was to identify the components of decision
      making among the dialysis patients. Subjects were a Convenience sample of
      hemodialysis patients who agreed to participate this study. The data was
      collected through semi-structured interviews was recorded on the tape and
      transcribed. Decision-making episodes were picked and interpreted by researchers.
      Data was analysed based on the Grounded Theory Approach. RESULT: Subject were 21
      patients from 4 hospitals. The mean age was 51.1 and the mean duration after the
      hemodialysis was 9.1 years. The number of episode of decision-making were 136.
      Six components of decision-making were extracted such as <goal> <recognition of
      situation> <recognition of self> <choice> <planning> <evaluation>. The subject
      were making decision by examining and judging the situation and oneself, and then
      setting the goal. They were selecting situation and themselves. After all, the
      outcomes of decision-making were evaluating. Seven type of decision-making,
      erection type, reality-oriented type, elaborate type, dogmatic type, passive
      type, chance type, resistant type were extracted. DISCUSSION: The factors which
      were related to the quality of decision-making were discussed such as the ability
      to examine the reality and control own wishes and needs, and the commitment for
      the decision-making. The nursing approach to facilitate the patients to make the
      decision were mentioned.

PMID- 9274371
TI  - [The effect on bowel sounds of very hot compresses applied to the lumbar region].
AB  - In Japan, very hot moist compresses applied to the lumbar region have been used
      to promote intestinal movement and flatus or defecation. This skill was based on
      empirical knowledge. One of the purposes of this study is to make clear the
      effect of very hot compresses on intestinal movement. The other purpose is to
      prove the safety of the skin where very hot compresses applied. The sample
      consisted of 8 healthy female volunteers, ranging in age from 27 to 47 with a
      mean age of 37.4. A very hot compress was applied to the lumbar region for 10
      minutes. The results were as follows: 1) Bowel sounds immediately after hot
      compresses increased 1.7 times compared with bowel sounds before the hot
      compresses. 2) Skin temperature of the back increased to 41.1-43.1 degrees
      centigrade under the hot compresses, then decreased rapidly. 3) Blood flow to the
      back during hot compresses, increased to 156%. Blood flow to the upper arm also
      increased. 4) Body temperature, pulse rate and blood pressure were not remarkably
      changed by the hot compresses. The results of the experiments show that very hot
      compresses applied to the lumbar region affect intestinal movement. And the
      results suggest that a very hot compress is a useful nursing skill to promote
      flatus or defecation.

PMID- 9274372
TI  - [Social support of chronically-ill children and healthy children].
AB  - The purpose of this study was to describe characteristics of social support of
      chronically-ill children and to compare social support of chronically-ill
      children with those of healthy children. Subjects consisted of 204 chronically
      ill children aged between 9 and 18 years old and 544 healthy children aged
      between 10 and 17 years old. Results of this study were as follows: 1. In both
      chronically-ill children and healthy children, parents' support score and
      teachers' support score were significantly higher in elementary school children
      than high school students. In both groups, friends' support score was
      significantly higher in girls than boys. 2. Chronically-ill children reported
      significantly higher scores of parents' support, friends' support and teachers'
      support than those of healthy children. 3. Parents' support score was
      significantly lower in children with diabetes than those with asthma and cancer.
      4. The total score of social support and teachers' support score were
      significantly lower in children with employed mothers than those with unemployed
      mothers. 5. The total social support score of children who participated in non
      sports extracurricular activities was significantly higher than those of children
      who did not participate in non-sports activities.

PMID- 9274373
TI  - [The meaning and structure of cancer survivors' perception of their health].
AB  - The purpose of this study is to examine the meaning and structure of cancer
      survivors' perception of their health. An ethnographic approach is used in an
      inductive analysis of survivors' behavior. Thirty cancer survivors were examined
      through interviews and participant observation (participant observation was
      conducted in their own homes, offices, outpatient departments, or at the meetings
      of survivors' self-help groups). The cancer survivors' perceptions of their
      health, described in their own words, are categorized in 17 "folk domains of
      concepts". Among them, category A, "kekkyoku-wa-jibun-da (After all, there is
      nobody but me)" was selected as the tentative theme: the remaining domains were
      reorganized by their relationship with this theme domain. Through this study, it
      was found that the theme domain plays an important role when a cancer survivor
      struggles for survival and arrives at a state in which extraordinary
      circumstances brought about by cancer do not bother him any longer. This findings
      indicates that sound recovery from cancer can be achieved through harmony between
      a cancer survivor's self and his daily life. This also suggests that help should
      be provided to cancer survivors to contribute to stable surroundings that enable
      them to establish a sound self concept.

PMID- 9274374
TI  - [Recent problem of trans fatty acids in human milk].

PMID- 9274375
TI  - [A study on supporting methods for house-bound home care elderly to get
      independent life (1st report)--relation between ADL and daily hours out of bed].
AB  - It is important to prevent the House-Bound home care elderly from getting worse
      to the Bed-bound. We studied the relation between "daily hours out of bed" and
      the activity of daily living (ADL) estimated by FIM (Functional Independence
      Measure) in 50 house-bound home care elderly persons. Result are as follows; (1)
      The level of independence of "Toileting", one of the FIM self-care items, was
      most highly correlated with the "daily hours out of bed" in the house-bound home
      care elderly. (2) The level of independence of "Mobility to the Toilet" and
      "Bowel Control" were also highly correlated with the "daily hours out of bed" in
      the house-bound home care elderly. (3) The level of independence of "Toileting"
      had high correlation with a total score of FIM moter items in the house-bound
      home care elderly (r = 0.83, p < 0.001).

PMID- 9274376
TI  - [Effects of intermittent wakening on sleep pattern of nighttime caregiver: an EEG
      study with a single subject].
AB  - In order to investigate the effects of night wakening on sleep pattern of
      caregiver, a woman aged 45 years was studied using electroencephalogram (EEG).
      After two adaptation nights, her all-night EEG readings were recorded for six
      nights. During the first three consecutive nights, the subject slept by the side
      of a patient at a private ward of hospital and wakened by herself several times a
      night to provide care for the patient (care nights). Of the later three nights,
      her sleep EEGs were recorded at her home (free nights). The first free night was
      following three care nights and the other two free nights were after 2 weeks. The
      results were summarized as follows; 1) Sleep period time (SPT) of care nights
      differed in different nights. In contrast to the SPT range of 356-367 min during
      free nights, it was 271-391 min during the care nights. 2) The rhythm of sleep
      cycles of care nights was not stable, though the subject wakened by herself, not
      using an alarm clock. 3) Although there were few changes occurring in sleep
      efficiency (SE) and percent each stage for SPT (%SPT) between the first and
      second care night, SE of the third care night was more similar to SE of free
      nights than SE of the first two care nights, and so was %SPT of the third care
      night. 4) Sleep latency (SL) decreased during the four consecutive nights, i.e.
      the three care nights and the first free night, and SL of the third care night
      and the first free night were shorter than SL of the last two free nights. The
      accumulation of fatigue and stress of nighttime care was suggested.

PMID- 9274399
TI  - HLA and trachoma.

PMID- 9274400
TI  - Dry eye.

PMID- 9274401
TI  - Outcome measures for glaucoma treatment.

PMID- 9274402
TI  - Future shock: the long-term consequences of refractive surgery.

PMID- 9274403
TI  - HLA antigens in Omanis with blinding trachoma: markers for disease susceptibility
      and resistance.
AB  - AIM: To determine the presence of HLA antigens in people with blinding trachoma.
      METHODS: Fifty Omanis with blinding trachoma were serologically typed for HLA A,
      B, C, DR, and DQ antigens and DNA typed for class II DR beta and DQ beta alleles
      and compared with a population of 100 healthy controls. RESULTS: chi 2 analysis
      of serological reactions did not reveal any significant differences in HLA
      antigen frequencies after correction of probability, although DR4, DR7, and DR53
      were completely absent in the patients and all of the patients were HLA DQ1
      positive. In the case of DQ1 the relative risk was 22.6 (95% confidence interval
      of 20.7-24.7). Class II DNA low resolution DR beta typing showed a significant
      increase in HLA DR16 (pc = 0.036, relative risk = 3.8) and a significant decrease
      in HLA DR53 (pc = 0.018, relative risk = 0.05). CONCLUSION: The finding that HLA
      DR16 (a DR2 subtype) is associated with susceptibility to blinding trachoma, a
      disease that is caused by an intracellular micro-organism, is consistent with
      reports of an HLA DR2 association with leprosy and tuberculosis, diseases also
      caused by an intracellular micro-organism. Similarly, resistance to leprosy is
      associated with HLA DR53 as is the case with blinding trachoma described here. It
      is postulated that HLA DR2 or subtypes in association with HLA DQ 1 may enable an
      intracellular micro-organism to enter the cell or are involved in presentation of
      peptides derived from intracellular micro-organisms to T lymphocytes initiating a
      delayed hypersensitivity or autoimmune reaction. These findings are the first
      report that genetic factors are of major importance in the development and
      protection against blinding trachoma.

PMID- 9274404
TI  - Long-term course of tear gland function in patients with keratoconjunctivitis
      sicca and Sjogren's syndrome.
AB  - AIMS: To assess the course of tear gland function of patients with
      keratoconjunctivitis sicca (KCS) associated with primary (KCS-PSS) or secondary
      Sjogren's syndrome (KCS-SSS), and of patients with KCS not related to Sjogren's
      syndrome (KCS-NS). METHODS: In 106 patients with dry eye an ophthalmic diagnosis
      of KCS was made. Subsequent evaluations revealed a diagnosis of KCS-PSS in 31,
      KCS-SS in 19, and KCS-NS in 56 patients. Follow up assessments have been
      performed 10-12 years after initial diagnosis. RESULTS: At baseline and at follow
      up tear gland function tests were worse in patients with KCS-PSS compared with
      the other forms of KCS. At follow up in the KCS-SSS patient group the tear gland
      function variables returned to marginal normal limits. In contrast with
      expectation, a marked improvement of the tear gland function variables in the KCS
      NS patient group was noted. CONCLUSIONS: In KCS-PSS patients tear gland function
      is characterised by a steady state situation. In KCS-SSS patients the
      normalisation of tear gland function variables most probably reflects a remission
      of the underlying disease. In view of the overall improvement in KCS-NS patients
      the term age related KCS should be avoided.

PMID- 9274405
TI  - Dry eye and Meige's syndrome.
AB  - AIMS: To determine the relation between dry eye and Meige's syndrome. METHODS:
      325 patients with dry eye were divided into those responsive to topical and other
      forms of treatment (n = 276) and those who were not (n = 49). A neuropsychiatric
      examination was performed to check for Meige's syndrome in the latter group.
      RESULTS: Twenty eight (57%) of the treatment unresponsive patients were diagnosed
      with Meige's syndrome. CONCLUSIONS: There is a subgroup of patients with dry eye
      who do not respond to simple therapy. More than half of these patients have
      Meige's syndrome and need psychiatric, as well as ophthalmic, care.

PMID- 9274406
TI  - Blindness and visual impairment in a region endemic for onchocerciasis in the
      Central African Republic.
AB  - AIMS: A population based survey of blindness and visual impairment was conducted
      in the district of Bossangoa, Central African Republic. METHODS: A total of 48
      communities were randomly selected, and 6086 people examined. RESULTS: The
      prevalence of blindness (visual acuity in the better eye less than 3/60) was
      2.2%, and visual impairment 3.0% (6/24 to 3/60 in the better eye). The major
      causes of blindness were onchocerciasis (73.1%), cataract (16.4%), trachoma
      (4.5%), and glaucoma (2.2%). CONCLUSION: Around 95.5% of all blindness could
      potentially have been prevented or treated. Ivermectin mass distribution is hoped
      to prevent 50% of all forms of visual loss in the future.

PMID- 9274407
TI  - Measurement of intraocular pressure after epikeratophakia.
AB  - AIMS: To assess the accuracy of three commonly used tonometers in eyes after
      epikeratophakia. METHODS: Five eye bank eyes with sutured epikeratophakia buttons
      were connected to a manometer and a pressure transducer. Intraocular pressure was
      adjusted in 5 mm Hg increments from 0 to 50 mm Hg. The intraocular pressure was
      measured at each increment using a Goldmann tonometer, a pneumatonometer, and a
      Tono-pen. RESULTS: The difference between the manometer (actual pressure) and the
      Goldmann tonometer ranged from -19 to +9 mm Hg (mean (SD) overestimation 2.6
      (5.8) mm Hg). The pneumatonometer error ranged from -27.5 to +5.5 mm Hg (mean
      (SD) overestimation 4.7 (6.1) mm Hg), and for the Tono-pen the range was -18 to
      +11 mm Hg (mean (SD) overestimation 0.05 (7.9) mm Hg). The correlation
      coefficients for the three tonometers were 0.94, 0.92, and 0.87 for the Goldmann
      tonometer, pneumatonometer, and Tono-pen respectively. CONCLUSION: The Goldmann
      tonometer had the best correlation with the manometer in eye bank eyes with
      epikeratophakia (correlation coefficient 0.94), but none of the tonometers was
      accurate over the entire range of pressures tested. Detection of glaucoma in eyes
      with epikeratophakia cannot rely on tonometry alone, but requires examination of
      the optic nerve and visual field.

PMID- 9274408
TI  - High spatial resolution automated perimetry in glaucoma.
AB  - BACKGROUND: Automated perimetry is of fundamental importance in assessing visual
      function in glaucoma. A technique was evaluated to perform high spatial
      resolution automated perimetry to allow a more detailed assessment of the
      luminance sensitivity in selected regions of the visual field than is possible
      with conventional perimetry. METHOD: High spatial resolution perimetry was
      performed using a Humphrey automated perimeter by measuring luminance sensitivity
      across a 9 by 9 degree custom grid of 100 test locations with a separation
      between adjacent locations of 1 degree. Quantitative analysis of the raw and
      Gaussian filtered thresholds was performed to assess the repeatability of the
      technique in normals, glaucoma suspects, and glaucoma patients. RESULTS: The
      testing protocol was well tolerated by all subjects. High spatial resolution
      perimetry in glaucomatous eyes demonstrated fine luminance sensitivity loss not
      suspected with conventional perimetry. High spatial resolution perimetry also
      demonstrated reproducible areas of sensitivity loss in some glaucomatous eyes in
      areas of the visual field which appear normal with conventional programmes. The
      repeatability of the technique correlated with mean threshold sensitivity and was
      substantially improved to clinically acceptable levels by Gaussian filtering the
      thresholds. CONCLUSION: This technique of high spatial resolution perimetry
      allows the practical assessment of selected regions of the visual field at higher
      resolution than conventional perimetry, and may be clinically useful in glaucoma.

PMID- 9274409
TI  - Ultrasound biomicroscopic measurement of anterior chamber angle in premature
      infants.
AB  - AIM: To establish normative values for the anterior segment in premature infants
      in relation to postconceptional age and birth weight. METHODS: Anterior segments
      were measured in 39 premature infants, 25 to 39 weeks' gestational age by use of
      ultrasound biomicroscopy and a muscle hook with topical anaesthesia. RESULTS:
      Anterior chamber depth, trabecular-iris angle, angle opening (trabecular-iris)
      distances at 250 and 500 microns from the scleral spur, and the thickness of the
      thickest part of the iris showed linear increases in relation to postconceptional
      age and birth weight. CONCLUSIONS: Ultrasound biomicroscopy is a powerful tool
      for obtaining precise images and measurement of the anterior segment in preterm
      neonates. Normative values were established for anterior segment dimensions in
      relation to postconceptional age and birth weight.

PMID- 9274410
TI  - Screening for amblyopia: a comparison of paediatric letter tests.
AB  - AIMS/BACKGROUND: The measurement of visual acuity is the most widely accepted
      indicator of amblyopia and is thought by some to be the only effective screening
      test. The aim of this study was to investigate the effectiveness of the
      traditional single optotype Sheridan-Gardiner test (SGT) in the measurement of
      visual acuity and the detection of amblyopia, compared with the log based linear
      format Glasgow acuity cards (GAC). METHODS: In the present study visual acuity
      was measured monocularly in 702 primary 1 schoolchildren using both acuity tests.
      RESULTS: A significant difference was found in the mean (SD) visual acuity
      measured with GAC (0.9 (0.08) modified logMAR) and SGT (1.13 (0.09) modified
      logMAR), df = 632, t = -59.08, p = 0.0001. The majority of children (89.3%)
      achieved visual acuities better than 6/6 in either eye when using the single
      optotype test. If the 95% confidence limits for a significant interocular
      difference in acuity are used as-criteria for the detection of unilateral
      amblyopia, GAC were found to be the most sensitive, correctly identifying 100%,
      while SGT identified 55% of the children with unilateral amblyopia. CONCLUSION:
      The results of this study highlight several problems with both the test format
      and testing procedure in the present school screening system.

PMID- 9274411
TI  - A novel pattern of oculocerebral malformation.
AB  - AIMS/BACKGROUND: To report a novel pattern of oculocerebral malformation related
      to the group of diseases characterised by cobblestone lissencephaly. METHODS: By
      means of a case report with specialist descriptions of the novel
      neuropathological and ophthalmic pathology features. RESULTS: The patient, born
      to healthy consanguineous parents, presented in the neonatal period with
      jaundice, convulsions, and macrocephaly. Computed tomography demonstrated
      hydrocephalus and abnormal cerebral gyration. Ophthalmic examination revealed
      severe myopia and segments of retinal atrophy. Cytogenetic investigation revealed
      a balanced reciprocal translocation (46,XX,t(5p11;19q13.1)) that was inherited
      from the mother and was present in several normal relatives. Mild short stature
      and profound mental handicap were evident. The child died aged 7 years. At
      necropsy the brain showed 'cobblestone' (type II) lissencephaly. Cerebellar
      cortical architecture was abnormal and the brain stem lacked cerebral peduncles,
      basis pontis, and pyramids. Biopsies of skeletal muscles were normal. The ocular
      abnormalities included discrete sectors of retina of varying thickness with
      disordered neuronal lamination and gliosis. The optic nerve was gliotic and
      contained few nerve fibres. The anterior iris surface was studded with cellular
      stromal nodules which appear to be melanocytic in nature. CONCLUSION: Retinal
      dysgenesis occurs in the group of syndromes with 'cobblestone lissencephaly', the
      best known being Walker-Warburg syndrome. In this case, relatively long survival,
      lack of muscular dystrophy, and novel ocular pathology distinguish it from the
      other diagnoses in this group of syndromes. We suggest this child was affected by
      a distinct and novel oculocerebral syndrome.

PMID- 9274412
TI  - Frequency characteristics of accommodation in a patient with agenesis of the
      posterior vermis and normal subjects.
AB  - AIMS: To clarify the cerebellar control of accommodation in humans, the frequency
      characteristics of accommodation were studied in a patient with agenesis of the
      posterior cerebellar vermis and four age matched normal subjects. METHODS:
      Magnetic resonance imaging of the brain of the 29 year old patient showed
      agenesis of the vermis and paravermis of lobules VIII-X and hypoplasia of the
      vermis and paravermis of lobules I-VII, the cerebellar hemisphere, and the
      cerebellar nuclei. The gain and phase lag of accommodative responses for
      sinusoidally modulated blur stimuli were calculated for the patient and four
      normal subjects. The blur stimuli consisted of predictable simple sinusoids of
      3.0 dioptres at a frequency of 0.05, 0.1, 0.2, 0.3, 0.5, or 1.0 Hz. RESULTS: The
      frequency characteristics of accommodative responses in the patient have a larger
      phase lag and a smaller gain at higher frequencies than those in the four normal
      subjects. CONCLUSIONS: These findings suggest that the cerebellum contributes to
      the control of accommodation by improving the frequency characteristics at high
      frequencies.

PMID- 9274413
TI  - Decreased choriocapillaris perfusion following surgical excision of choroidal
      neovascular membranes in age-related macular degeneration.
AB  - AIMS/BACKGROUND: To evaluate macular changes following surgical excision of
      subfoveal choroidal neovascular membranes (CNVs) in age-related macular
      degeneration (AMD). METHODS: The clinical records, fluorescein angiograms, and
      CNV histopathology of 12 patients with AMD who underwent surgical excision of
      subfoveal CNV were reviewed. RESULTS: New areas of decreased choriocapillaris
      perfusion were noted by fluorescein angiography in the previous location of the
      CNV in 8/12 (75%) cases. Surgically excised tissue contained retinal pigment
      epithelium (RPE) in 11/11 specimens and choriocapillaris in 1/11 specimen
      studied. CONCLUSIONS: Choriocapillaris atrophy may partly underlie the limited
      visual outcome following subfoveal surgery for AMD. Abnormal choriocapillaris
      perfusion following CNV excision may be due to pre-existing choriocapillaris
      atrophy, to choriocapillaris damage or removal at the time of surgery, or to RPE
      removal at surgery with abnormal RPE repopulation of the dissected area and
      subsequent choriocapillaris degeneration.

PMID- 9274414
TI  - Pathology of iris in leprosy.
AB  - AIM: The histopathological features of the iris in leprosy were studied by light
      microscopy. METHOD: Formalin fixed and paraffin embedded iris tissue excised
      during cataract surgery from 20 leprosy patients were sectioned and studied with
      haematoxylin and eosin stain and modified Fite Faraco's stain for acid fast
      bacilli (AFB). RESULTS: Chronic inflammatory reactions were seen in the iris of
      11 patients, seven of whom did not have any clinically demonstrable evidence of
      iridocyclitis. Smooth muscle disruption and destruction were seen in two
      specimens. AFB were found in the iris tissue of a polar lepromatous patient whose
      skin smears were negative for AFB and who had completed the WHO recommended
      antileprosy multidrug therapy (MDT). CONCLUSION: Histopathology discloses far
      more silent chronic iridocyclitis in leprosy patients than are diagnosed
      clinically. AFB can persist in the iris tissue even after completion of MDT.
      Smooth muscle disruption and destruction, a cause of the miotic pupil in leprosy
      has been conclusively demonstrated histopathologically.

PMID- 9274415
TI  - Microsatellite instability and loss of heterozygosity in human pterygia.
AB  - AIMS/BACKGROUND: Pterygium is a common benign lesion of the corneoconjunctival
      limbus. Although environmental factors, such as ultraviolet irradiation, have
      been suggested as the main causative factor in the development of the disease,
      however, the aetiopathology of pterygium remains obscure. In this study the
      possibility of detecting genetic alterations in the microsatellite DNA of the
      pterygium was investigated. METHODS: Fifteen specimens were assessed for for loss
      of heterozygosity (LOH) and microsatellite instability (MI) by seven
      microsatellite markers on four chromosomal arms. RESULTS: Nine (60%) pterygia
      exhibited genetic alterations. Eight specimens (53%) exhibited LOH, while two
      specimens (13%) MI in at least one marker. 17q11.2-q21 is a commonly deleted
      region, as the frequency of LOH at this region is significantly high (47%).
      CONCLUSION: This finding indicates the existence of tumour suppressor genes in
      this region implicated in the disease without excluding the presence of other
      tumour suppressor genes in the other chromosomal regions that were examined. MI
      was apparent in only a few specimens but it is indeed a detectable phenomenon,
      suggesting that decreased fidelity in DNA replication and repair may be
      associated with the development of pterygium. Detection of LOH and MI, two events
      taking place in tumour cells or in premalignant cells, constitutes strong
      evidence that there must be transformed cells in the pterygial tissue and it
      should be considered to be a neoplastic benign lesion.

PMID- 9274416
TI  - Polymerase chain reaction for detection of Chlamydia trachomatis in conjunctival
      swabs.
AB  - AIMS/BACKGROUND: Ocular Chlamydia trachomatis infection in the west occurs as
      opthalmia neonatorum, acquired from the mother, or adult paratrachoma which is
      also associated with current genital tract infection. Accurate rapid laboratory
      diagnosis facilitates management, but the relative merits of antigen detection or
      DNA amplification tests are unresolved. METHODS: A polymerase chain reaction
      (PCR) test was developed which amplified part of the plasmid shared by all the
      serovars of C trachomatis. Conjunctival swabs were tested using an in house
      immune dot-blot test (IDBT) for chlamydial lipopolysaccharide antigen, a
      commercial direct fluorescent antibody (DFA) test for chlamydial elementary
      bodies, and the PCR (DNA extracted using guanidinium lysis buffer). RESULTS: The
      PCR achieved a detection limit of 100 plasmid copies (10 elementary bodies). In a
      combined retrospective and prospective clinical evaluation, the PCR and IDBT gave
      identical results with 21 positive and 57 negative eye swabs. However,
      interpretation of the DFA test required meticulous examination of the stained
      smear, sometimes by two microscopists. CONCLUSIONS: The PCR is likely to play an
      increasing role in the diagnosis of ocular C trachomatis infection because of its
      excellent sensitivity and specificity.

PMID- 9274418
TI  - Spontaneous dissection of internal carotid artery presenting as isolated
      posterior ischaemic optic neuropathy.

PMID- 9274419
TI  - Posterior scleritis with optic perineuritis and internal ophthalmoplegia.

PMID- 9274420
TI  - Corneoscleral laceration associated with passenger-side airbag inflation.

PMID- 9274421
TI  - Keratoconjunctivitis after exposure to party foam.

PMID- 9274423
TI  - Anterior segment ischaemia after excision of conjunctival squamous cell
      carcinoma.

PMID- 9274422
TI  - Donor corneo-scleral rim cultures after organ culture.

PMID- 9274425
TI  - Euphorbia sap keratouveitis.

PMID- 9274424
TI  - Pseudocystic ultrasound appearance of choroidal melanoma.

PMID- 9274417
TI  - Role of vascular permeability factor/vascular endothelial growth factor in eye
      disease.

PMID- 9274426
TI  - Elimination of trachoma.

PMID- 9274427
TI  - Thymus therapy for cancer.

PMID- 9274428
TI  - The usefulness of screening data for studying the biology of breast cancer.

PMID- 9274429
TI  - Is histological grading of value for the prognosis of soft tissue sarcomas?

PMID- 9274430
TI  - Radiotherapy-induced second cancers: are we doing enough to protect young
      patients?

PMID- 9274431
TI  - Thymus therapy for cancer? A criteria-based, systematic review.

PMID- 9274432
TI  - Colorectal cancer--is there an alternative to 5-FU?

PMID- 9274433
TI  - Androgens and prostate cancer: biology, pathology and hormonal therapy.

PMID- 9274434
TI  - Progress in the management of T3-4 adenocarcinoma of the prostate.

PMID- 9274435
TI  - The assessment of treatment outcomes in metastatic prostate cancer: changing
      endpoints.

PMID- 9274436
TI  - Evolving strategies of cytotoxic chemotherapy for advanced prostate cancer.
AB  - Despite the use of cytotoxic chemotherapy for advanced prostate cancer for half a
      century, its clinical utility in this setting remains undefined. Based on
      traditional methods of assessment, the list of the most active cytotoxic agents
      includes cyclophosphamide, doxorubicin, mitoxantrone and cisplatin. With the
      introduction of more structured methods of assessment, including careful
      assessment of indices of quality of life and serial measurement of serum prostate
      specific antigen (PSA), the role of cytotoxic agents is being re-assessed. In
      view of the cell cycle characteristics of prostate cancer, there appears to be an
      emerging role for combination inhibitors of mitosis, including estramustine in
      combination with the vinca alkaloids, etoposide or paclitaxel.

PMID- 9274437
TI  - Why are cancer patients using non-proven complementary therapies? A cross
      sectional multicentre study in Norway.
AB  - This study addressed the use of alternative medicine, here called non-proven
      therapies (NPTs), among hospitalized Norwegian cancer patients. A total of 126
      (20%) of the assessable 630 patients were users of NPTs. Approximately 43% of all
      patients and more than 60% of the users of NPTs stated that they would like NPTs
      to be an option in hospitals belonging to the National Health Service. Most users
      of NPTs (82%) consulted traditional medicine first, while 15% started treatment
      with NPTs simultaneously. Users of NPTs reported to have received less hope of a
      cure (30%) from their physicians than non-users (50%). Users mostly learned about
      NPTs from friends and relatives. Most users believed that NPTs might give them
      strength and relieve their symptoms. Very few patients believed in a cure (10%).
      Nearly 40% were uncertain of any effect of the NPTs or felt there had been no
      effect. 4 patients reported adverse effects. 15 patients had been treated abroad,
      most of them in Denmark. Expenses incurred through use of NPTs were mostly
      moderate, but some patients used large sums of money. Patients' opinions on
      whether or not the treatment had been expensive were closely linked to their
      anticipation of the effect of the treatment.

PMID- 9274438
TI  - S-phase fractions of breast cancer predict overall and post-relapse survival.
AB  - We studied the correlation of S-phase fraction (SPF) with clinical outcome in 127
      pre- or perimenopausal patients with breast cancers treated by neoadjuvant
      chemotherapy from October 1986 to June 1990. When the patients were analysed
      using the median value of the SPF as a threshold, there was a small but non
      significant difference in favour of low SPF tumours for metastasis-free survival.
      SPF was the only parameter predicting overall survival in multivariate analysis
      (P < 0.002) which included T, N, histopathological grade and steroid hormone
      receptors. The results of metastasis-free survival contrasted with previous
      analyses with shorter follow-up, so we tested the time-dependent influence of SPF
      on prognosis. It was thus shown that SPF significantly predicts metastasis-free
      survival only during the first 30 months, whereas the relative risk of cancer
      related death according to SPF remains significant for 56 months. In order to
      find an explanation for the difference in predictivity between metastasis-free
      survival and overall survival, we studied the post-relapse survival.
      Significantly shorter survival (median 12 months) was associated with tumours
      presenting pre-treatment high SPF values, compared to the low SPF group for which
      60% of the patients were still alive after 30 months of metastasis phase (P =
      0.002). Our current results, in a homogeneous series with a median follow-up of
      over 5 years, emphasise the importance of proliferation-related parameters for
      breast cancer management.

PMID- 9274439
TI  - The minimal effective exemestane dose for endocrine activity in advanced breast
      cancer.
AB  - Phase I studies have demonstrated that exemestane, an irreversible oral aromatase
      inhibitor, is able to suppress circulating oestrogen levels. In our previous
      experience, doses ranging from 2.5 to 25 mg induced a similar suppression of
      oestrogens. The aim of this study was to identify the minimum effective
      exemestane dose on the basis of endocrine activity. 20 evaluable postmenopausal
      advanced breast cancer patients were randomly given exemestane 0.5, 1, 2.5 or 5
      mg, in double-blind conditions. Oestrone (E1), oestradiol (E2), oestrone sulphate
      (E1S), gonadotrophins, sex-hormone binding globulin and dehydroepiandrosterone
      sulphate serum levels were evaluated from the first day of treatment to the 7th,
      14th, 28th and 56th day. Serum E1, E2 and E1S levels were suppressed by all doses
      starting from day 7; the degree of inhibition versus baseline was 25 up to 72%
      for E1, 30 up to 62% for E2 and 16 up to 52% for E1S, with higher doses achieving
      greater suppression; these changes were maintained over time. A significant
      increase in FSH and LH levels was observed for all doses. Treatment tolerability
      was satisfactory. The endocrine effects of exemestane appear to be dose related
      and 0.5 and 1 mg are ineffective for adequately suppressing circulating
      oestrogens.

PMID- 9274440
TI  - A phase I-II trial of fixed-dose carboplatin and escalating paclitaxel in
      advanced ovarian cancer.
AB  - We conducted a phase I-II study with escalating paclitaxel doses plus carboplatin
      at a fixed dose for previously untreated patients with advanced ovarian cancer in
      order to define the maximum tolerated dose. Eligible for the study were women
      with a histologically confirmed diagnosis of ovarian cancer stage III-IV
      according to the FIGO classification. In the first phase of the study, 6 patients
      were allocated escalating paclitaxel doses with fixed-dose carboplatin in order
      to establish the maximum tolerated dose. The starting dose of paclitaxel was 150
      mg/m2 given after carboplatin (300 mg/m2) every 4 weeks for a total of six
      courses. The paclitaxel dose step was 25 mg/m2 up to 250 mg/m2. The study then
      progressed to a phase II trial using the maximum tolerated paclitaxel dosage
      reached during the escalating dose phase. A total of 27 patients entered phase I
      and 23 phase II. Neurotoxicity was observed in 47 patients (94%; 29 grade 1, 17
      grade 2, 1 grade 3, according to the WHO classification). The intensity of
      neurotoxicity tended to be dose related: out of the 15 patients who received < or
      = 200 mg paclitaxel, a total of 14 grade 1, but no grade 2 or 3 neurotoxicities,
      were observed. The frequency of grade 1, 2 and 3 neurotoxicity was 15, 17 and 1,
      respectively, in the 35 women who received > or = 225 paclitaxel +300 mg
      carboplatin. There was no clear relationship between median WBC and platelet
      nadir and dose level. Among other toxicities, alopecia was observed in all 50
      cases, hypersensitivity in two (4%) and myalgia in 41 (82%; 34 grade 1 and 7
      grade 2). These frequencies tended to increase with the dose, but the
      relationship was not statistically significant. The overall response rate was 78%
      (39/50) with a complete response rate of 62% (31/50). In conclusion, this study
      suggests that carboplatin and paclitaxel can be administered safely to patients
      with advanced ovarian carcinoma. The maximum dose reached was 250 mg/m2
      paclitaxel and 300 mg/m2 for carboplatin, but from a clinical point of view the
      maximum paclitaxel dose we would consider safe is 225 mg/m2.

PMID- 9274441
TI  - Rhabdomyolysis and renal function impairment after isolated limb perfusion-
      comparison between the effects of perfusion with rhTNF alpha and a 'triple-drug'
      regimen.
AB  - The aim of this study was to monitor serum and perfusate levels of myoglobin (MB)
      and creatine kinase (CK) during isolated limb perfusion (ILP) in order to
      identify those at risk of renal failure. We investigated the release of MB and CK
      in 40 patients who underwent ILP for melanoma (n = 15) or sarcoma (n = 25) using
      rhTNF alpha/melphalan (n = 28) or a triple-drug regimen (n = 12). Serial
      determinations of CK and MB were performed in both perfusate and systemic
      circulation during and after ILP and renal function was assessed. A significant
      increase of MB could be detected in the perfusate during ILP. After ILP, an up to
      100-fold increase with a double peak of MB at 4 h and 24 h postoperatively was
      observed. The maximum elevation of serum activity of CK was at 30 h. The increase
      for both proteins was highly significant (P < 0.001). ILP with rhTNF
      alpha/melphalan yielded significantly (P < 0.001) higher serum values of MB and
      CK and also the impairment of the renal function was more pronounced. The peak
      values of MB after ILP occur early and allow the patients most at risk of
      developing renal failure to be identified. Rhabdomyolysis can be detected early
      by determination of MB from the perfusate. Further measurements twice daily for 2
      3 days post ILP from serum samples as well as daily assessment of MB in the urine
      is helpful for detecting myoglobinuria and imminent renal failure.

PMID- 9274442
TI  - Medroxyprogesterone acetate reduces the in vitro production of cytokines and
      serotonin involved in anorexia/cachexia and emesis by peripheral blood
      mononuclear cells of cancer patients.
AB  - Medroxyprogesterone acetate (MPA) is widely used in oncology both in the
      treatment of hormone-related cancers and as supportive therapy in
      anorexia/cachexia syndrome (ACS), but conclusive data are not yet available to
      explain its anticachectic effect. ACS is characterised by weight loss, changes in
      metabolism, reduction of appetite, nausea and vomiting. Several cytokines, mainly
      interleukin (IL)-1, IL-2, IL-6 and tumour necrosis factor alpha (TNF alpha), are
      involved in the pathogenesis of ACS. Additionally, nausea and vomiting can be
      mediated by factors inducing serotonin (5-HT) production and/or release by
      pleiotropic cells including activated T lymphocytes. In the present study, we
      report the effect of MPA on peripheral blood mononuclear cells (PBMC) from 10
      cancer patients in advanced stage of disease (6 head and neck, 2 colon, 1 lung
      and 1 ovary). The proliferative response of PBMC to PHA, anti-CD3 monoclonal
      antibody (MAb) or recombinant IL-2 (rIL-2), the production of IL-1 beta, IL-2, IL
      6, TNF alpha and 5-HT by PHA-stimulated PBMC and the expression of lymphocyte
      membrane-bound IL-2 receptor (IL-2R) subunities (CD25 and CD122) were studied.
      The addition of MPA significantly reduced the PBMC proliferative response to PHA
      and anti-CD3 MAb but not to rIL-2. MPA 0.2 microgram/ml was also capable of
      reducing the levels of IL-1 beta, IL-6, TNF alpha and 5-HT produced in culture by
      PHA-stimulated PBMC, whereas it did not induce any change in the percentage of
      PBMC expressing either CD25 or CD122 or both molecules after stimulation with PHA
      or anti-CD3 mAb.

PMID- 9274443
TI  - Mitotic percentage index: a new prognostic factor for childhood medulloblastoma.
AB  - We investigated the prognostic significance of a new method of mitotic figure
      quantitation, 'mitotic percentage index' (MPI), tumour S phase fraction (SPF) and
      DNA ploidy measured by flow cytometry, and various clinical prognostic factors
      including age, sex, tumour stage, degree of surgical resection, radiotherapy dose
      and adjuvant chemotherapy in 70 cases of childhood medulloblastoma diagnosed
      between 1968 and 1996. In univariate analysis, MPI (P < 0.0001), posterior fossa
      radiotherapy dose (P = 0.003), tumour stage (P = 0.014), craniospinal
      radiotherapy dose (P = 0.019), year of diagnosis (P = 0.024) and SPF (P = 0.048)
      were significantly related to survival. In multivariate analysis, including
      tumour c-erbB-2 oncogene product expression, only MPI (P < 0.0001), craniospinal
      radiotherapy dose (P = 0.003) and tumour stage (P = 0.035) retained independent
      prognostic significance, while age achieved significance (P = 0.039). A close
      relationship was observed between MPI and SPF (coeff = 0.8, P < 0.0001) and MPI
      and the percentage of tumour cells expressing the c-erbB-2 oncogene product
      (coeff = 0.416, P < 0.0001). This study has identified MPI as a new independent
      prognostic factor for childhood medulloblastoma. Its close relationship with
      tumour SPF confirms it as an accurate measure of tumour proliferation and its
      close relationship to expression of the c-erbB-2 oncogene supports a role for
      this growth factor receptor in the deregulation of normal mitogenic signal
      transduction in this malignancy.

PMID- 9274444
TI  - Childhood cancer incidence in Zaragoza and Navarre (Spain): 1973-1987.
AB  - Patterns and trends in childhood cancer incidence for Navarre and Zaragoza
      registries were studied over the 15-year period, 1973-1987. Overall cancer rates
      and rates for 10 specific types of cancer were analysed using a log-linear
      Poisson model or, alternatively, a gamma-Poisson model whenever overdispersion
      was present, with age, sex, registry and period being used as predictor
      variables. Childhood cancer was 30% more frequent in boys than in girls, and,
      except for lymphomas and bone tumours, incidence decreased remarkably with age.
      Adjusted rates were high in comparison with other European countries,
      particularly in the case of non-Hodgkin's lymphomas. Cancer rates proved somewhat
      higher in Navarre, but this difference attained statistical significance solely
      in the case of central nervous system tumours (rate ratio = 1.75; 95% confidence
      interval 1.21-2.54). A significant rise in overall incidence was observed (11% 5
      yearly increase) due mainly to the upward trend in central nervous system
      tumours. While the rise in these tumours coincides with the period which
      witnessed the spread of computerised tomography in Spain, the trend nevertheless
      held steady over the last 5-year period, when access to this diagnostic technique
      had already become generalised nationwide.

PMID- 9274445
TI  - Mammographic screening for breast cancer. What cancers do we find?
AB  - The aim of this study was to compare lymph node involvement of breast cancer
      cases detected at mammography screening with clinically-detected cases. During a
      3-year period, 273 primary breast cancers were detected in a population-based
      screening programme, and 149 primary breast cancers were diagnosed clinically.
      Lymph node involvement was evaluated in univariate and multivariate logistic
      regression models correcting for tumour size, histological grade, steroid
      receptor status and DNA-ploidy. Patients with screen-detected cancers had a low
      relative risk of having lymph node metastases (univariate, OR = 0.31; 95%
      confidence interval = 0.19-0.52). In the multivariate logistic regression model,
      the relative risk was halved (OR = 0.47; 0.28-0.78). The reduced risk was more
      pronounced for women younger than 50 years of age compared to older women. The
      risk for screen-detected cases of having lymph node metastases at diagnosis was
      statistically significantly lower than for clinically-detected cases. The marked
      reduction, even when correcting for tumour size, makes it less likely that
      factors such as detection of clinically innocent tumours, length bias sampling or
      clinical symptoms related to axillary metastases can explain the whole
      difference. The results indicate at least part of the effect may be explained by
      tumour progression in the late preclinical detectable phase.

PMID- 9274446
TI  - Attributable risks for hepatocellular carcinoma in northern Italy.
AB  - The population attributable risks (ARs) for hepatocellular carcinoma (HCC) were
      estimated in relation to low education level, heavy alcohol consumption, low
      vegetable and fruit intake, history of hepatitis, diabetes, liver cirrhosis and
      oral contraceptive use, using data from a case-control study conducted between
      1984 and 1993 in Northern Italy. Cases were 320 patients (235 males and 85
      females) with histologically or serologically confirmed HCC, and controls were
      1408 patients (1031 males and 377 females) admitted to the same network of
      hospitals for acute, non-neoplastic or non-digestive tract conditions, unrelated
      to any of the known or likely risk factors for primary liver cancer. The ARs were
      40% for low vegetable and fruit consumption, 31% for low education, 18% for liver
      cirrhosis, 16% for hepatitis, 8% for diabetes and 7% for heavy alcohol
      consumption. Together, these factors explained 74% of hepatocellular cancer
      cases. Compared with females, males had higher ARs for cirrhosis (21% versus
      11%), diabetes (10% versus 2%) and heavy alcohol consumption (9% versus 1%). The
      percentage of HCC attributable to all factors considered together was 78% for
      males and 67% for females. Thus, even if available information on hepatitis and
      dietary factors was limited, and the AR estimates were based on several arbitrary
      assumptions, available knowledge could, in principle, reduce the burden of the
      disease in Italy from 3300 deaths to approximately 750 for males, and from 1600
      to approximately 500 for females.

PMID- 9274447
TI  - Homeobox genes: molecular link between congenital anomalies and cancer.
AB  - Homeobox-containing genes play a major role in the control of segmental identity
      during embryonic development in Drosophila. Abnormalities of these genes have
      been shown to produce a wide variety of congenital anomalies in invertebrates and
      in vertebrates. Many transgenic mice, which are mutant for homeobox genes, show a
      specific skeletal abnormality, similar to the human cervical rib. In humans, a
      relationship exists between malformations and tumours. Human cervical rib has
      been shown to be associated with an increased incidence of malignancy. Recent
      evidence indicates that homeobox genes might also play a role in carcinogenesis.
      In this article, we explore the possibility that alterations of homeobox genes
      might be the basic underlying aetiology for the association between congenital
      malformations and tumours, at least in a proportion of cases. We provide evidence
      in support of this argument and suggest areas of further research which would
      confirm this concept.

PMID- 9274448
TI  - Inhibition of telomerase activity by cisplatin in human testicular cancer cells.
AB  - Telomerase, a ribonucleoprotein, elongates and/or maintains telomeres by adding
      TTAGGG tandem repeat sequences using the RNA component of the enzyme as a
      template. Enzyme activity appears to be associated with cell immortalisation and
      malignant progression as telomerase activity has been found in the majority of
      human tumours, but not in most somatic cells or tissues. Telomerase inhibition
      has, therefore, been proposed as a novel and potentially selective target for
      therapeutic intervention. Since telomeric tandem repeats as well as the human
      telomerase RNA component (hTR) and its gene are guanosine-rich, we examined
      whether the sequence specific, G-Pt-G, cross-linking agent cisplatin is capable
      of inhibiting telomerase activity. The TRAP assay was used to measure telomerase
      activity in cisplatin treated cell extracts and RT-PCR strategies used to examine
      hTR expression after drug exposure. Cisplatin reduced telomerase activity in a
      specific and concentration-dependent manner in human testicular tumour cells,
      whilst doxorubicin, bleomycin, methotrexate, melphalan and transplatin had no
      effect. It is proposed that telomerase inhibition might be a component of the
      efficacy of cisplatin in the treatment of testicular cancer.

PMID- 9274449
TI  - Hypofractionated radiation induces a decrease in cell proliferation but no
      histological damage to organotypic multicellular spheroids of human
      glioblastomas.
AB  - The aim of this study was to examine the effect of radiation on glioblastoma,
      using an organotypic multicellular spheroid (OMS) model. Most glioblastoma cell
      lines are, in contrast to glioblastomas in vivo, relatively radiosensitive. This
      limits the value of using cell lines for studying the radiation effect of
      glioblastomas. The advantage of OMS is maintenance of the characteristics of the
      original tumour, which is lost in conventional cell cultures. OMS prepared from
      four glioblastomas were treated with hypofractionated radiation with a
      radiobiologically equivalent dose to standard radiation treatment for
      glioblastoma patients. After treatment, the histology as well as the cell
      proliferation of the OMS was examined. After radiation, a significant decrease in
      cell proliferation was found, although no histological damage to the OMS was
      observed. The modest effects of radiation on the OMS are in agreement with the
      limited therapeutic value of radiotherapy for glioblastoma patients. Therefore,
      OMS seems to be a good alternative for cell lines to study the radiobiological
      effect on glioblastomas.

PMID- 9274450
TI  - Co-expression of MDR-associated markers, including P-170, MRP and LRP and
      cytoskeletal proteins, in three resistant variants of the human ovarian carcinoma
      cell line, OAW42.
AB  - Variants of the human ovarian carcinoma cell line, OAW42, exhibiting low-level
      intrinsic resistance (OAW42-SR) and drug-induced higher-level resistance (OAW42
      A1 & OAW42-A), were studied along with a sensitive clonal population (OAW42-S)
      which was isolated from OAW42-SR. Expression of the MDR-associated protein P-170,
      the more recently discovered LRP (lung resistance-related protein) and MRP
      (multidrug resistance-associated protein), topoisomerase II alpha and beta, GST
      pi and the cytoskeletal proteins, cytokeratin 8 and vimentin, were studied (using
      immunocytochemistry and Western blotting techniques) in conjunction with drug
      (doxorubicin) accumulation and subcellular distribution. Expression of mRNA for P
      170, MRP, topoisomerase 11 alpha and beta and GST pi was studied using RT-PCR
      (reverse transcriptase polymerase chain reaction). Results indicate differential
      co-expression of four MDR-associated parameters (P-170, MRP, LRP and reduced
      topoisomerase II alpha and beta) in the OAW42-SR and OAW42-A1 variants, whereas
      resistance in the OAW42-A variant appeared to be mainly P-170 mediated.
      Comparable amounts of MRP and greater amounts of LRP were detected in the OAW42-S
      cells compared to the OAW42-SR variant (which showed increased resistance
      compared to the OAW42-S cells), but all cell lines expressed similar low-level
      amounts of MRP mRNA (by RT-PCR). GST pi levels did not differ markedly between
      variants. Increased levels of the cytoskeletal proteins were observed with
      increasing levels of resistance. The relative resistance of the variants, OAW42
      SR and OAW42-A1, compared with OAW42-S was seen to change during increased serial
      passaging of the cells. There was greater drug accumulation by the sensitive
      OAW42-S cell line compared with that of the resistant variants, particularly the
      most highly resistant OAW42-A cells. Both verapamil and cyclosporin A effectively
      restored the accumulation defects seen in the resistant variants, cyclosporin A
      being the more effective of the two. Sub-cellular location of drug was
      predominantly in the nucleus with maximum levels seen in the sensitive OAW42-S
      variant and minimum levels in the most resistant OAW42-A clone.

PMID- 9274451
TI  - Endothelin expression and responsiveness in human ovarian carcinoma cell lines.
AB  - To elucidate the potential role of endothelins (ETs) as growth regulators in
      ovarian carcinoma cells in culture, expression of endothelins and their receptors
      were measured in two ovarian cancer cell lines (PEO4 and PEO14), together with
      the effect of the exogenous addition of endothelins on the growth of these cell
      lines in vitro. RT-PCR analysis of mRNA prepared from PEO4 and PEO14 indicated
      the presence of ET-1 and ET-3 mRNA. Immunoreactive ET-1-like peptide was found in
      media from cultures of both PEO4 (1.7 +/- 0.4 fmol/10(6) cells/72 h) and PEO14
      (20.2 +/- 6.8 fmol/10(6) cells/72 h) cell lines. Radioligand binding studies
      using 125I-ET-1 and membrane fractions were consistent with PEO4 cells having two
      receptor sites of either high affinity (Kd = 0.065 nM, Bmax = 0.047 pmol/mg
      protein) or lower affinity sites (Kd = 0.49 nM, Bmax = 0.23 pmol/mg protein).
      Studies using membrane fractions of PEO14 cells indicated that this cell line has
      only a single lower affinity binding site (Kd = 0.56 nM, Bmax = 0.31 pmol/mg
      protein). However, RT-PCR analysis indicated the presence of mRNA from both ETA
      and ETB receptors in PEO4 and PEO14 cell lines. Exogenous addition of ETs to PEO4
      and PEO14 cells at concentrations of 10(-10)-10(-7)M resulted in specific dose
      dependent increases in cell number for ET-1 (with maximum effects at 10(-10) and
      10(-9)M for PEO4 and PEO14, respectively) and ET-2 (maximum effects at 10(-8) and
      10(-9)M for PEO4 and PEO14, respectively) but not for ET-3. Experiments on the
      growth of PEO14 cells using BQ123 (ETA-R) antagonist and "antisense"
      oligonucleotide against the ETA-R, in the absence of exogenous ETs, suggested
      that immunoreactive ET-1-like material secreted by PEO14 cells can affect their
      growth in an autocrine manner. These results would be consistent with ET-1 acting
      as a possible autocrine growth regulator in human ovarian carcinoma cells.

PMID- 9274452
TI  - Modulation of cis-diamminedichloroplatinum (II) accumulation and cytotoxicity by
      spermine in sensitive and resistant human ovarian carcinoma cells.
AB  - The effect of spermine (Sp), a natural polycationic amine, on cisplatin (CDDP)
      sensitivity and accumulation of a human ovarian CDDP-sensitive cell line (2008)
      and its resistant variant (C13*) was investigated. Survival was also studied. The
      C13* cells were approximately 20-fold resistant to CDDP, yet were found to be
      just as sensitive to Sp as 2008 cells. When Sp was concurrently added with CDDP
      to the colony-forming assay, the IC50 dose was approximately 3-fold lower than
      that of CDDP alone. This decrease was the result of a synergistic interaction, as
      assessed by median effect analysis. The incubation of cells with the approximate
      IC50 dose of Sp for 1-8 h indicated that this synergism could be due to
      stimulation of CDDP accumulation, showing maximal uptake after 4 h of Sp
      exposure. This stimulation may be the result of a modulation of cellular membrane
      permeability by Sp, as assessed by the accumulation of [3H]mannitol. Exposure to
      Sp concentrations active on CDDP uptake also significantly increased [3H]mannitol
      accumulation in both cell lines. The triamine spermidine (Spd) did not
      significantly affect either the sensitivity of the two cell lines or CDDP and
      [3H]mannitol accumulation. These results suggest that Sp is a positive modulator
      of CDDP uptake, and thus of its cytotoxicity, even in resistant cells, where the
      phenotype is partly due to a CDDP accumulation defect.

PMID- 9274453
TI  - Hydrogen peroxide is involved in lymphocyte activation mechanisms to induce
      angiogenesis.
AB  - T-lymphocytes from tumour-bearing mice are able to trigger the angiogenic
      cascade. Since it is known that tumour growth produces reactive oxygen species
      (ROS), the aim of this study was to evaluate the role of hydrogen peroxide (H2O2)
      on the activation of lymphocytes and their induction of this vascular response.
      Studies on lymphocytes, stimulated in vitro by ROS to induce angiogenesis, showed
      that only the enzyme catalase (CAT) could block the activation. The incubation of
      normal lymphocytes with H2O2 stimulated these cells to induce angiogenesis. The
      administration of H2O2 or an oxidative stress-producing drug (doxorubicin) to
      normal mice activated in vivo angiogenesis. In tumour-bearing mice, high levels
      of lipid peroxidation products were observed in the spleen, but not in the liver
      or kidney. Moreover, when the ROS scavenger enzyme activities (superoxide
      dismutase (SDM) and CAT) were determined, we observed low CAT activity in normal
      spleens, reflected in a high SDM/CAT ratio, when compared to liver or kidney
      values. We also showed an increasing value of the SDM/CAT ratio with tumour
      growth. These results strongly suggest that H2O2 could be involved in the
      mechanisms of lymphocyte activation and their induction of angiogenesis during
      tumour growth.

PMID- 9274454
TI  - BRCA1 mutations found in archived early onset breast tumours.
AB  - Inherited mutations in the BRCA1 gene are thought to account for approximately 5%
      of breast cancers in women under the age of 45 years. In order to determine
      whether mutations could be found at the expected frequency, 60% of the protein
      coding region of BRCA1 was screened in 75 archived early-onset breast tumours,
      taken from women under 45 years of age. Two of the 75 tumours (2.7%) had
      detectable mutations, in close agreement to that predicted. Since BRCA1 mutations
      found in breast tumours are invariably germline, two immediate consequences are
      apparent. Firstly, family members of affected patients are likely to carry
      mutations as well, and should be considered for BRCA1 screening; and secondly,
      persons harbouring a germline BRCA1 mutation should be examined frequently and
      indefinitely for new primary tumours in remaining breast tissue.

PMID- 9274455
TI  - Doxifluridine in colorectal cancer patients resistant to 5-fluorouracil (5-FU)
      containing regimens.
AB  - Doxifluridine (5-dFUR) is a fluoropyrimidine derivative, which is preferentially
      converted to 5-fluorouracil (5-FU) within tumour tissues. Although the activity
      of 5-FU in metastatic colorectal cancer is well recognised, resistance to this
      agent is frequently observed and remains its major limitation. The aim of this
      phase II study was to evaluate the activity of oral and i.v. 5-dFUR in metastatic
      or locally advanced colorectal cancer patients, who had been previously treated
      with a 5-FU containing regimen in either an adjuvant or metastatic setting. We
      treated 48 patients who, on the basis of tumour progression during, or within 8
      weeks of the discontinuation of 5-FU therapy, were considered 5-FU resistant, 14
      of the patients received 5-dFUR 3000 mg/m2 as a 1-h i.v. infusion, combined with
      L-leucovorin 25 mg/dose on days 1-5, every 3 weeks; the remaining 34 received
      oral 5-dFUR 1200 mg/m2 for 5 days followed by 5 days off. Oral L-leucovorin 25
      mg/dose was administered 2 h before 5-dFUR. On the basis of WHO criteria, 4/14
      (29%, 95% CI 4-51) partial responses were noted in the i.v. treated patients, and
      4/34 (12%, 95% CI 1-23) in those treated orally. The radiological examinations
      documenting the response were a CT scan in 4 cases, ultrasound in 2 and NMR in 2.
      The median response duration was 6 months (range 3-11+), whereas the median time
      to treatment failure was 4 months (range 2-17). The responses were achieved in
      cases previously treated with a median of 9250 mg/m2 (range 5500-18,650) of 5-FU.
      No CTC-NC1 grade 4 toxicity was observed, although grade 3 diarrhoea occurred in
      5 of the orally treated and in 3 of the intravenously treated patients. This is
      the first report documenting the efficacy of 5-dFUR in patients resistant to 5-FU
      therapy, and suggests that there is an absence of complete cross-resistance
      between these two fluoropyrimidines.

PMID- 9274456
TI  - Prognostic value of basic fibroblast growth factor and its receptor (FGFR-1) in
      patients with non-small cell lung carcinomas.
AB  - Tumour specimens of 206 patients with untreated non-small cell lung carcinomas
      (NSCLC) were analysed immunohistochemically for the expression of the basic
      fibroblast growth factor (bFGF) and for its receptor (FGFR-1, Flg). Seventy of
      the tumours showed weak expression, 109 moderate and 27 high expression of bFGF.
      Thirty-eight tumours had low expression of FGFR-1, 116 had moderate and 52 cases
      high expression. Patients with high FGFR-1 expression had significantly shorter
      survival times than patients with weak or moderate expressions (P < 0.05), but
      there was no significant correlation between bFGF expression and patient
      survival. The results of the multivariate analysis demonstrated that FGFR-1 in
      the presence of stage is not an independent prognostic factor.

PMID- 9274457
TI  - Role of radical prostatectomy in micrometastases dissemination.

PMID- 9274458
TI  - Clinical benefit with cisplatin, hydroxyurea and 5-fluorouracil/leucovorin in
      advanced pancreatic adenocarcinoma.

PMID- 9274459
TI  - Radiation-recall dermatitis with docetaxel: establishment of a requisite
      radiation threshold.

PMID- 9274460
TI  - Cathepsin D content in malignant tumours of corpus uteri.

PMID- 9274461
TI  - Research misconduct.

PMID- 9274462
TI  - Treatment of autoimmune hepatitis.

PMID- 9274463
TI  - Photodynamic therapy in gastroenterology.

PMID- 9274464
TI  - Current European concepts in the management of Helicobacter pylori infection. The
      Maastricht Consensus Report. European Helicobacter Pylori Study Group.
AB  - There is considerable confusion over the management of Helicobacter pylori
      infection, particularly among primary care physicians, and numerous European
      countries lack national guidelines in this rapidly growing area of medicine. The
      European Helicobacter Pylori Study Group therefore organised a meeting in
      Maastricht of H pylori experts, primary care physicians and representatives of
      National Societies of Gastroenterology from Europe to establish consensus
      guidelines on the management of H pylori at the primary care and specialist
      levels, and to consider general health care issues associated with the infection.
      As in previous guidelines, eradication therapy was recommended in all H pylori
      positive patients with peptic ulcer disease. Additionally, at the primary care
      level in dyspeptic patients < 45 years old and with no alarm symptoms, diagnosis
      is recommended by non-invasive means (13C urea breath test, serology) and if H
      pylori positive the patient should be treated. Moreover, at the specialist level
      the indications for eradication of H pylori were also broadened to include H
      pylori positive patients with functional dyspepsia in whom no other possible
      causes of symptoms are identified by the specialist (after a full investigation
      including endoscopy, ultrasound and other necessary investigations), patients
      with low grade gastric mucosa associated lymphoid tissue (MALT) lymphoma (managed
      in specialised centres) and those with gastritis with severe macro- or
      microscopic abnormalities. There was consensus that treatment regimens should be
      simple, well tolerated and achieve an eradication rate of over 80% on an
      intention to treat basis. It was strongly recommended, therefore, that
      eradication treatment should be with proton pump inhibitor based triple therapy
      for seven days, using a proton pump inhibitor and two of the following:
      clarithromycin, a nitroimidazole (metronidazole or tinidazole) and amoxycillin.

PMID- 9274465
TI  - Enhancement of photodynamic therapy in gastric cancer cells by removal of iron.
AB  - BACKGROUND: Aminolaevulinic acid (ALA) is an endogenous substrate in the haem
      biosynthetic pathway. Protoporphyrin IX (PPIX), the immediate haem precursor in
      the pathway, has photoexcitable properties. Exogenous ALA has been used
      previously as a precursor agent in photodynamic therapy (PDT). Its main advantage
      is a short half-life and hence reduced incidence of skin photosensitivity. ALA
      can be toxic, however, causing, for example, transient increases in liver enzyme
      concentrations when given systemically and this may be dose related. AIM: To
      assess whether accumulation of PPLX and ultimately the efficacy of PDT could be
      improved by modulating both ends of the haem biosynthetic pathway. METHODS:
      Gastric cancer cells (MKN 28) were incubated with ALA (0-1000 mumolar) and
      desferrioxamine (0-800 mumolar) for 24 hours before exposure to argon-pumped dye
      laser (630 nm) at different energy levels (0-40 J/cm2). Cell viability was
      assessed by use of the methyl-tetrazolium (MTT) assay four hours after exposure
      to light. RESULTS: Total PPIX accumulation increased linearly with increasing
      extracellular concentrations of ALA up to 1 mmolar (r = 0.973, p < 0.005). Adding
      200 molar of desferrioxamine trebled PPIX accumulation over the same period of
      incubation. Cell viability after exposure to light decreased with low doses (0-30
      mumolar) of desferrioxamine (r = 0.976, p = 0.024). However, higher doses of
      desferrioxamine (more than 40 molar) seemed to confer a protective effect against
      PDT. CONCLUSION: PDT using ALA can be improved by removal of available iron with
      desferrioxamine. The reason for the protective effect of desferrioxamine seen at
      higher doses is not clear.

PMID- 9274466
TI  - Effect of sucralfate on aspirin induced mucosal injury and impaired haemostasis
      in humans.
AB  - BACKGROUND: Sucralfate does not have potent anti-ulcerogenic actions in users of
      non-steroidal anti-inflammatory drugs (NSAIDs). However, sucralfate may influence
      intragastric haemostasis favourably. AIM: To investigate separately the effects
      of sucralfate on acute gastric and duodenal injury and on changes in intragastric
      bleeding induced by aspirin. METHOD: On three occasions, 24 healthy volunteers
      received three days' treatment with aspirin 900 mg twice daily together with
      placebo, sucralfate 2 g twice daily or sucralfate 1 g four times daily. Injury
      was assessed endoscopically and bleeding by spontaneous and biopsy induced
      bleeding intragastric washings. Ex vivo prostaglandin E2 (PGE2) synthesis and
      serum thromboxane were measured by using radioimmunoassay. RESULTS: Aspirin
      significantly inhibited ex vivo gastric mucosal PGE2 synthesis, reduced serum
      thromboxane, caused gastric erosions, and increased spontaneous and biopsy
      induced bleeding. Sucralfate had no significant effects on endoscopic injury but
      sucralfate 1 g four times daily significantly reduced spontaneous and biopsy
      induced bleeding. Similar trends were seen with sucralfate 2 g twice daily but
      the results were less consistent. CONCLUSION: Sucralfate does not affect aspirin
      induced acute gastric mucosal injury but reduces aspirin associated intragastric
      bleeding.

PMID- 9274468
TI  - Effect of curing Helicobacter pylori infection on intragastric acidity during
      treatment with ranitidine in patients with duodenal ulcer.
AB  - BACKGROUND: In patients with duodenal ulcer cure of Helicobacter pylori infection
      resulted in a pronounced decrease in intragastric pH during treatment with
      omeprazole. AIM: To test the hypothesis that treatment of H pylori adversely
      affects the pH response to ranitidine. PATIENTS: Eighteen patients with duodenal
      ulcer who were infected with H pylori were studied. METHODS: Twenty four hour pH
      recordings were performed during treatment with ranitidine (300 mg) at night
      before and four to six weeks after cure of H pylori infection. Presence of H
      pylori was assessed by a rapid urease test, culture, histology, and a 13C urea
      breath test. Also, the fasting gastrin concentrations were measured before and
      after treatment for H pylori infection. RESULTS: Cure of H pylori infection
      resulted in a considerable improvement in both antral and corpus gastritis and a
      decrease in fasting gastrin concentrations. As a result of the cure the night
      time intragastric pH during treatment with ranitidine decreased (median pH 6.8 v
      5.4; p = 0.007), whereas the acidity during the daytime was not affected.
      CONCLUSIONS: In patients with duodenal ulcer the intragastric pH during treatment
      with ranitidine depends on H pylori. However, the loss of effectiveness in
      altering pH seems to be less pronounced than previously found with omeprazole.

PMID- 9274467
TI  - Relation between cholecystokinin and antral innervation in the control of gastric
      emptying in the rat.
AB  - BACKGROUND: Antral motility and the hormone cholecystokinin (CCK) are major
      determinants of the rate of gastric emptying. The relation between CCK and antral
      neurons in regulating gastric emptying is uncertain. Benzalkonium chloride (BAC)
      causes selective lesions in gut myenteric neurons after serosal application. AIM:
      To develop a model of antral denervation using BAC to enable the study of the
      relation between CCK and antral neurons in regulating gastric emptying. METHODS:
      BAC, vehicle or the afferent neurotoxin capsaicin were applied to the serosal
      surface of the rat antrum or corpus; neurochemical markers of intrinsic and
      afferent neurons were detected by using immunohistochemistry and
      radioimmunoassay. Gastric retention of solids was determined after fasting, and
      emptying of liquids was measured in rats with gastric fistulae. RESULTS: In BAC
      treated rats radioimmunoassay of tissue extracts revealed a dose related specific
      loss of gastrin releasing peptide, substance P, and vasoactive intestinal
      polypeptide immunoreactivities from the treated region, and immunohistochemistry
      revealed loss of the neuronal marker PGP 9.5 and the afferent neuropeptide
      calcitonin gene related peptide (CGRP). Adjacent untreated regions were
      unaffected by BAC, with the exception that CGRP was depleted in both corpus and
      antrum after antral treatment. After antral BAC treatment fasted rats retained
      solids for over 48 hours. Moreover, in antrally denervated rats with gastric
      fistulae, the emptying of saline, acid and peptone was delayed substantially. The
      CCK dependent inhibition of gastric emptying of peptone was preserved after
      antral treatment with BAC. CONCLUSIONS: Serosal BAC causes lesions in the
      innervation of the treated region of the stomach. The innervation of the antrum
      is essential for normal emptying of both liquids and solids, but the inhibition
      of gastric emptying produced by CCK is not dependent on antral neurons.

PMID- 9274469
TI  - Blood groups Lewis(b) and ABH expression in gastric mucosa: lack of inter
      relation with Helicobacter pylori colonisation and occurrence of gastric MALT
      lymphoma.
AB  - BACKGROUND: Blood group Lewis(b) antigens mediate Helicobacter pylori attachment
      to gastric mucosa with attachment being particularly strong in subjects with ABH
      blood group O. AIMS: To determine whether H pylori colonisation or the occurrence
      of gastric mucosa associated lymphoid tissue (MALT) lymphomas might be related to
      gastric Lewis(b) expression or occurrence of particular ABH blood groups on
      gastric mucosa. PATIENTS: Gastric resection specimens from 89 cases with gastric
      MALT lymphoma and gastric mucosal biopsy specimens from 95 patients undergoing
      upper endoscopy due to upper gastrointestinal complaints, including five cases
      with gastric MALT lymphoma, were studied. METHODS: H pylori was visualised with
      the Warthin-Starry stain. Immunostaining (Lewis(b), Lewis(a), A, B) was performed
      by applying a three step immunoperoxidase technique and indirect
      immunofluorescence staining on formalin fixed and paraffin wax embedded tissue.
      In 40 patients red blood cell Lewis phenotype and ABH blood groups were
      additionally determined by haemagglutination assay. RESULTS: Gastric surface
      epithelial cells showed an immunoreactivity to blood groups A, B, and AB in 80
      (43.5%), 22 (12%), and 11 (6%) cases respectively and no immunoreactivity to any
      of these blood group substances (blood group O) in 71 (38.5%) patients. Lewis(b)
      expression of all gastric surface epithelial cells (secretor status) was found in
      130 (70.7%) cases. Lewis(a) expression of all gastric surface epithelial cells
      (non-secretor status) was found in 36 (19.6%) cases, secretor status remained
      unclassified in 18 (9.8%) patients. Colonisation with H pylori was found in 134
      (72.8%) cases. The occurrence of H pylori was neither significantly associated
      with secretor status nor with certain ABH blood groups. The infiltration of
      gastric mucosa with MALT lymphoma was highly significantly associated with H
      pylori colonisation (p < 0.0003) but neither with secretor status nor with
      certain ABH blood groups. There was no inter-relation between secretor status or
      ABH blood groups and type, stage, grade of, and survival after MALT lymphoma.
      CONCLUSION: This study failed to show an inter-relation between secretor status
      or particular ABH blood groups and either H pylori infection or the occurrence of
      gastric MALT lymphomas.

PMID- 9274471
TI  - Prevention of Helicobacter pylori infection by lactobacilli in a gnotobiotic
      murine model.
AB  - BACKGROUND: Helicobacter pylori is a bacterium which causes gastric inflammatory
      diseases. Oral inoculation of H pylori usually results in only a temporary
      colonisation without a successful infection in the stomach of conventional mice
      in which lactobacilli are the predominant indigenous bacteria. AIM: To determine
      whether lactobacilli exert an inhibitory effect on colonisation by H pylori in
      the stomach. METHODS: The effects of H pylori on attachment to murine and human
      gastric epithelial cells and the H pylori mediated release of interleukin-8 (IL
      8) by these cells were examined in vitro. Lactobacillus salivarius infected
      gnotobiotic BALB/c mice and control germ free mice were inoculated orally with H
      pylori to examine whether L salivarius can inhibit colonisation by H pylori.
      RESULTS: L salivarius inhibited both the attachment and IL-8 release in vitro. H
      pylori could not colonise the stomach of L salivarius infected gnotobiotic BALB/c
      mice, but colonised in large numbers and subsequently caused active gastritis in
      germ free mice. In addition, L salivarius given after H pylori implantation could
      eliminate colonisation by H pylori. CONCLUSION: These findings suggest the
      possibility of lactobacilli being used as probiotic agents against H pylori.

PMID- 9274470
TI  - Does treatment of Helicobacter pylori with antibiotics alone heal duodenal ulcer?
      A randomised double blind placebo controlled study.
AB  - BACKGROUND: Treatment of Helicobacter pylori infection prevents duodenal ulcer
      relapse. It has not been established if treatment of the infection heals duodenal
      ulcer. AIM: To test the hypothesis that treatment of the infection was associated
      with healing of duodenal ulcer. METHODS: A randomised, double blind placebo
      controlled trial was performed to study the efficacy of an antibiotic only
      regimen consisting of 300 mg metronidazole, 500 mg amoxycillin, and 250 mg
      clarithromycin, each given four times daily for two weeks, in the healing of
      duodenal ulcer as assessed by endoscopy. Symptoms were controlled with
      acetaminophen and antacids. RESULTS: Of 100 consecutive patients with
      endoscopically established duodenal ulcer, 97 with positive rapid urease test on
      antral biopsy specimens were admitted into the study and 81 completed the trial.
      Of these, 40 were randomised to receive antibiotics and 41 to receive placebo.
      Treatment with antibiotics resulted in 92.5% (95% confidence interval (95% CI)
      84.3-100) healing at four weeks and 100% at eight and 12 weeks; the corresponding
      healing rates for placebo treatment were respectively, 36.6%, 61%, and 63.4% (95%
      CIs 21.8-51.3, 46.0-75.9, and 48.7-78.2 respectively). The differences between
      the two treatment groups were significant at p < 0.001 at each time point and by
      life table analysis. Clearance of H pylori as assessed by urease test on antral
      biopsy specimens at four weeks and eradication of the organism as determined by
      13C-urea breath test at eight weeks were achieved in 85% and 62.5% of patients
      respectively. Duodenal ulcer healed at four weeks in 87.2% and 86.2% (95% CIs
      76.7-97.7 and 73.7-98.8) of patients in whom H pylori clearance or eradication,
      was achieved, versus 42.9% and 51.9% (95% CIs 27.9-57.8 and 38.3-65.5; p < 0.001
      and < 0.003 respectively) in whom these processes failed. Stepwise discriminant
      analysis on 32 clinical, personal, and endoscopic characteristics as well as H
      pylori clearance and eradication identified H pylori clearance as the most
      discriminative variable for the healing of duodenal ulcer at four weeks, followed
      by ulcer depth and eradication of the organism. CONCLUSIONS: Treatment with an
      antibiotic only regimen was effective for the healing of duodenal ulcer, and
      clearance as well as eradication of H pylori contributed significantly to the
      healing. The results constituted the strongest evidence to date that H pylori
      infection was aetiologically related to duodenal ulceration, and support the
      concept of treating duodenal ulcer associated with H pylori as an infection and
      relieving its symptoms with acid reducing agents such as antacids.

PMID- 9274472
TI  - Nutrient regulation of human intestinal sugar transporter (SGLT1) expression.
AB  - BACKGROUND: The activity of most intestinal nutrient transporters is adaptively
      regulated by the type and amounts of nutrients entering the intestinal lumen. The
      concentration and activity of the intestinal Na+/glucose cotransporter (SGLT1)
      are regulated by dietary sugars in most animal species. The activity and
      abundance of SGLT1 in biopsy specimens removed from human jejunal regions exposed
      to, and having limited access to, luminal nutrients have been measured and
      compared. AIMS: To study the effects of luminal nutrients on the expression of
      SGLT1 in the human intestine. PATIENT AND METHODS: Brush border membrane vesicles
      (BBMV) were prepared from biopsy specimens removed from the intestine of a 50
      year old man who had developed a high output jejunal fistula, and adjacent
      mucosal fistula, a condition present for 12 months after surgery for a
      strangulated hernia. BBMV prepared from intestine exposed to luminal nutrients,
      and from dysfunctional intestine with a limited exposure to nutrients, were used
      to measure Na+ dependent glucose transport and abundance of SGLT1 protein.
      RESULTS: The levels of SGLT1 activity and abundance in the BBMV prepared from
      control biopsy specimens were similar to those found in BBMV prepared from the
      intestine of healthy individuals. BBMV from the dysfunctional intestine, exposed
      to limited levels of luminal nutrients, had reduced levels of SGLT1 activity.
      This reduction in SGLT1 activity and abundance was above that associated with any
      villus atrophy, as assessed by the abundance/activity of lactase and villin
      concentrations. CONCLUSIONS: These data indicate that the activity and expression
      of SGLT1 in human intestine is maintained by the presence of luminal nutrients.

PMID- 9274473
TI  - Gut lavage IgG and interleukin 1 receptor antagonist:interleukin 1 beta ratio as
      markers of intestinal inflammation in children with inflammatory bowel disease.
AB  - BACKGROUND: Whole gut lavage is currently used as preparation before radiological
      or endoscopic examination of the large bowel. AIM: To validate the gut lavage
      technique for the assessment of mucosal inflammation, by measuring intestinal IgG
      and interleukin 1 beta (IL-1 beta) in the fluid obtained. PATIENTS: Sixteen
      children with Crohn's disease (CD), 14 with ulcerative colitis (UC), and 22 age
      matched controls. METHODS: Isotonic, non-absorbable polyethylene glycol based
      lavage solution was given orally or by nasogastric tube. Clear fluid was
      collected, filtered, and treated with protease inhibitors. IgG, IL-1 beta and IL
      1-receptor antagonist (IL-1-ra) were measured by sandwich enzyme linked
      immunosorbent assay (ELISA). RESULTS: In patients with UC and CD, IgG and IL-1
      beta levels were significantly (p < 0.001) higher than in controls. A positive
      correlation (p < 0.05) was found with disease activity scores. IL-1-ra levels
      were not significantly different in UC and CD, when compared with controls, but
      the IL-1-ra:IL-1 beta ratio was significantly (p < 0.01) lower in patients with
      UC and CD, and negatively (p < 0.001) correlated with IgG levels in lavage fluid.
      CONCLUSIONS: Gut lavage fluid IgG and IL-1 beta levels and IL-1-ra:IL-1 beta
      ratio may provide objective discrimination between active and inactive disease in
      children with inflammatory bowel disease.

PMID- 9274474
TI  - Measles virus serology in Crohn's disease.
AB  - BACKGROUND: There is evidence that measles virus infection in early life may
      predispose to Crohn's disease. AIMS: To examine using serological methods a
      potential association between measles virus infection in early life and
      predisposition to Crohn's disease. SUBJECTS: Forty five patients with Crohn's
      disease and forty five healthy controls were studied prospectively. METHODS:
      Clinical data were recorded and serum was analysed for measles virus,
      cytomegalovirus (CMV), adenovirus and herpes simplex virus (HSV) antibody titres
      by a complement fixation test (CFT), and for measles virus IgM by enzyme linked
      immunosorbent assay (ELISA). RESULTS: Reciprocal CFT titres for measles virus
      were lower in patients with Crohn's disease compared with controls (p < 0.05);
      there was no significant difference in titres for other viruses. None of the
      subjects studied had a level of measles virus IgM suggestive of acute infection,
      and there was no significant difference in measles virus IgM levels between
      patients and controls. The measles virus CFT titres and IgM levels in the
      patients with Crohn's disease did not correlate with any of the clinical features
      recorded. CONCLUSION: This study does not provide supportive evidence for a role
      for measles virus in the aetiology of Crohn's disease.

PMID- 9274475
TI  - Influence of dietary protein supplements on the formation of bacterial
      metabolites in the colon.
AB  - BACKGROUND: To evaluate the influence of increased dietary protein intake on
      bacterial colonic metabolism in healthy volunteers. METHODS: Short chain fatty
      acids, ammonia, and volatile organic compounds in faecal samples, and phenols in
      the urine of five volunteers were measured after one week of basal nutrient
      intake and and after one week of a diet supplemented with a protein rich food
      (Fortimel; Nutricia, Zoetermeer, The Netherlands). Paired t tests and factor
      analysis were used for statistical analysis. RESULTS: Total energy and resistant
      carbohydrate intake remained unchanged in each study period. The percentage
      energy intake delivered as dietary protein, increased significantly (from 15.4%
      to 23.8%; p = 0.007) during supplement intake. A significant increase in faecal
      ammonia (p = 0.002), faecal valeric acid (p = 0.02), and urinary p-cresol (p =
      0.04) was noted during supplementary protein intake. A total of 120 different
      volatile compounds were isolated from the faecal samples of which 10 increased
      significantly during dietary protein supplementation. The change in volatile
      pattern, especially for S containing metabolites, was clearly shown by a factor
      analysis model which made a distinction between the two dietary regimens for all
      volunteers. CONCLUSION: An increase in dietary protein leads to altered products
      formation by colonic metabolism, mainly reflected by an increase in faecal
      ammonia, faecal volatile S substances, and urinary p-cresol.

PMID- 9274476
TI  - Effect of sulphide on short chain acyl-CoA metabolism in rat colonocytes.
AB  - BACKGROUND: It has been proposed that the diminished n-butyrate oxidation
      observed in ulcerative colitis may be the result of sulphide induced inhibition
      of short chain acyl-coenzyme A (acyl-CoA) dehydrogenase activity. AIM: To examine
      the acyl-CoA ester profiles in isolated rat colonic epithelial cells treated in
      vitro with sodium hydrogen sulphide (NaHS). METHODS: Isolated rat colonic
      epithelial cell suspensions were incubated for 10 minutes in the presence of [1
      14C] n-butyrate (5 mM), with and without NaHS (1.5 mM). Incubations were carried
      out both in the presence and the absence of exogenous CoA and ATP. Metabolic
      performance was assessed by 14CO2 production and by acyl-CoA ester production
      measured by HPLC with ultraviolet detection. RESULTS: Results are given as mean
      (SEM). For colonocytes incubated in the presence of exogenous CoA and ATP,
      treatment with NaHS significantly diminished 14CO2 production (control 0.97
      (0.06) mumol/g dry weight cells/min, treated 0.26 (0.09) mumol/g dry weight
      cells/min, p = 0.0019), was associated with an increase in butyryl-CoA
      concentrations in the final reaction mixture at 10 minutes (control 2.55 (0.28)
      mumol/g dry weight cells, treated 3.32 (0.32) mumol/g dry weight cells, p =
      0.002), and a reduction in crotonyl-CoA concentrations (control 0.274 (0.02)
      mumol/g dry weight cells, treated 0.120 (0.04) mumol/g dry weight cells, p =
      0.008). The mean concentration of acetyl-CoA in the reaction mixture at 10
      minutes was not significantly different between control and sulphide treated
      incubations. There were no significant differences in acyl-CoA ester profiles
      observed when cells were incubated in the absence of exogenous CoA and ATP.
      CONCLUSIONS: These results support the view that sulphides inhibit n-butyrate
      oxidation in colonic epithelial cells by inhibiting short chain acyl
      dehydrogenation of activated fatty acids.

PMID- 9274477
TI  - Does oesophageal motor function improve with time after successful antireflux
      surgery? Results of a prospective, randomised clinical study.
AB  - MAIN OBJECTIVE: There is a continuing debate whether motor abnormalities
      associated with gastro-oesophageal reflux disease (GORD) are primary phenomena or
      occur as a consequence of repeated injury caused by inflammation. To get new
      insights into mechanisms involved, patients were studied before and three years
      after effective and durable reflux control induced by two types of
      fundoplications. PATIENTS AND METHODS: Thirty three consecutive patients with
      chronic GORD entered the trial. All patients had a clinical history of GORD
      assessed symptomatically, endoscopically, and by use of 24 hour pH-metry.
      Eighteen were randomised to a 180 degrees semifundoplication (Toupet) and 15 to a
      total fundic wrap (Nissen-Rossetti). Manometry was done preoperatively, six
      months, and three years after the operation assessing motor function in defined
      areas of the tubular oesophagus and lower oesophageal sphincter. RESULTS: All
      patients had a proper control of GORD both when objectively and clinically
      assessed. Postoperatively, the resting tone of the lower oesophageal sphincter
      was significantly higher in the Nissen-Rossetti group (p < 0.05), and the intra
      abdominal portion of the lower oesophageal sphincter was of identical length in
      the two groups. A significant increase in peristaltic amplitude in the middle and
      distal third of the oesophagus was recorded at long term follow up compared with
      the preoperative findings (p < 0.05), but there was no corresponding effect on
      propagation speed and duration of contraction. However, an increase in
      peristaltic amplitude and, as a tentative consequence, a significant decrease (p
      < 0.05) in the frequency of primary peristalsis was found only in patients
      operated on with a total fundic wrap. CONCLUSION: Despite adequate and durable
      reflux control after fundoplication in patients with chronic GORD, no change was
      found in oesophageal motor function with time. The higher contraction amplitude
      and decreased frequency of failed primary peristalsis seen in patients having a
      total fundic wrap were thus most likely due to a mechanical outflow obstruction
      in the gastro-oesophageal junction. These results could therefore be interpreted
      in favour of the hypothesis that GORD is pathogenetically linked to a primary
      defect in oesophageal motor function.

PMID- 9274478
TI  - Achalasia: outcome of patients treated with intrasphincteric injection of
      botulinum toxin.
AB  - BACKGROUND: To evaluate the safety and clinical efficacy of botulinum toxin (BT)
      in patients with achalasia followed up for six months. METHODS: Fifty five
      symptomatic patients with manometrically proven achalasia were included in a
      multicentre prospective trial. Before and two weeks and two months after
      intrasphincteric injection of BT, symptoms of dysphagia, regurgitation, and chest
      pain were scored on a 0-3 scale, and lower oesophageal sphincter pressure (LOSP)
      was assessed. The symptom score was determined again at six months, clinical
      improvement being defined by < or = 3, relapse by > 3, and failure as a relapse
      after two injections or loss to follow up. RESULTS: Except for transient chest or
      epigastric pain (22%), no side effects were observed. There was a significant
      decrease in LOSP after treatment. Symptom scores were significantly improved at
      two weeks (2.0 (SD 1.6)), two months (1.7 (1.8)), and six months (1.9 (2.0))
      compared with pretreatment values (5.1 (1.8), p < 0.001). At six months, 33
      patients had clinical improvement (27 after one injection), 17 were considered
      failures, and five had just relapsed. Although there was a trend for age (older
      patients being more responsive), age, sex, prior duration of symptoms, initial
      symptom score, weight loss, LOSP, magnitude of oesophageal contractions, vigorous
      or non-vigorous achalasia, previous dilatations, and radiological features were
      not predictive of results. CONCLUSIONS: This multicentre series confirms that
      intrasphincteric injection of BT is a safe procedure, resulting in clinical
      improvement in 60% of patients with achalasia at six months. The therapeutic role
      of BT in achalasia needs further evaluation with regard to other alternatives.

PMID- 9274479
TI  - Clinical features of idiopathic megarectum and idiopathic megacolon.
AB  - BACKGROUND: Dilatation of the rectum and/or colon, in the absence of demonstrable
      organic disease, is an uncommon and poorly characterised condition. AIMS: To
      characterise the clinical and diagnostic features, and response to treatment, of
      patients with idiopathic megarectum (IMR) and idiopathic megacolon (IMC).
      METHODS: A retrospective review was undertaken of all patients operated on for
      these conditions over a 23 year period. In addition all patients treated over a
      three year period were prospectively studied by means of a questionnaire,
      contrast studies of the upper and lower intestine, spine x rays to exclude spinal
      dysraphism, anorectal physiological studies, and assessment of clinical outcome.
      Patients with Hirschsprung's disease and other known causes of gut dilatation
      were excluded. RESULTS: (i) Retrospective study: Of 63 operated patients, 22 had
      IMR, 23 had IMR and IMC, and 18 had IMC only. Five patients with IMC had previous
      sigmoid volvulus, and three had associated non-gastrointestinal congenital
      abnormalities. Faecal incontinence was always associated with rectal impaction
      and 14 patients (82%) with IMR alone had had manual disimpaction. (ii)
      Prospective study: Twenty two patients had IMR, with a median rectal diameter of
      10 cm (normal < 6.5 cm). Six patients had IMC and one patient had IMR and IMC.
      Patients with IMR were significantly (p = 0.0007) younger than patients with IMC.
      All patients with IMR became symptomatic in childhood, compared with half the
      patients with IMC who developed symptoms as adults. Patients with IMR all
      presented with soiling and impaction, compared with patients with IMC whose
      symptoms were variable and included constipation or increased bowel frequency,
      pain, and variable need for laxatives. No upper gut dilatation was seen in either
      group of patients. Spinal dysraphism was seen in two of 18 patients with IMR and
      two of four with IMC, suggesting extrinsic denervation as a possible cause in a
      minority. Twelve of 22 patients with IMR had a maximum anal resting pressure
      below normal, indicating sphincter damage or inhibition. Both IMR and IMC
      patients had altered rectal sensitivity to distension, suggesting that despite
      lack of dilatation the rectum in IMC has altered viscoelasticity, tone, or
      sensory function. Fifteen of 22 patients with IMR were successfully managed with
      laxatives or enemas, but seven required surgery. Two of seven patients with IMC
      required surgery, including one for sigmoid volvulus. CONCLUSIONS: Patients with
      IMR differ clinically, diagnostically, and in their outcome from patients with
      IMC. These conditions demand specific investigation, and intensive treatment, to
      achieve optimum care.

PMID- 9274480
TI  - DNA viruses in the pathogenesis of sporadic chronic idiopathic intestinal pseudo
      obstruction.
AB  - BACKGROUND: Hereditary forms of chronic idiopathic intestinal pseudo-obstruction
      (CIIP) are well described but the aetiology of most cases of sporadic CIIP is
      unknown. AIM: To determines whether herpes viruses can persist in the
      gastrointestinal tract, thereby implicating them in the pathogenesis of CIIP.
      METHODS: Twenty one specimens of small and large intestine from 13 patients with
      CIIP (eight visceral myopathy, three visceral neuropathy, two undifferentiated),
      and 12 patients operated on for colorectal cancer (controls) were examined for
      evidence of Herpesvirus DNA (cytomegalovirus, Epstein-Barr virus (EBV), herpes
      simplex virus type 1, and varicella zoster virus) by nested polymerase chain
      reaction (PCR) and in situ DNA hybridisation (ISH) to localise signal to the
      muscularis propria or myenteric plexus. RESULTS: Screening with nested PCR
      produced three patients with positive results. One patient with an inflammatory
      visceral neuropathy had EBV detected in the small intestine by PCR, and ISH
      demonstrated localisation to neurones in the myenteric plexus. A patient with a
      visceral myopathy had EBV DNA in both the small and large intestine; and one
      patient with a visceral neuropathy had small intestine positive for CMV DNA (both
      negative by ISH). No control tissue was positive for any virus. CONCLUSIONS: In
      individual patients there appears to be evidence linking a viral aetiology to
      sporadic CIIP. The role of neurotropic viruses in acute and chronic motility
      disturbances needs further study.

PMID- 9274481
TI  - Usefulness of somatostatin receptor scintigraphy in the management of patients
      with Zollinger-Ellison syndrome. Groupe de Recherche et d'Etude du Syndrome de
      Zollinger-Ellison (GRESZE).
AB  - BACKGROUND: Management of patients with Zollinger-Ellison syndrome (ZES) depends
      on the presence of multiple endocrine neoplasia type 1 (MEN 1) or liver
      metastases, or both. Somatostatin receptor scintigraphy (SRS) detects previously
      unknown endocrine tumours. AIM AND METHODS: To evaluate SRS findings susceptible
      to modifying the management of patients with ZES-that is, relevant findings, and
      the specificity of these findings. The latter were defined according to our
      current therapeutic strategy in three subgroups of patients (sporadic, MEN 1, and
      liver metastases). PATIENTS: 85 consecutive patients without known extra
      abdominal metastases were studied between September 1991 and March 1996. RESULTS:
      Relevant findings were found in 41% of 49 patients with sporadic disease but
      without liver metastases, in 22% of 18 patients with MEN 1 but without liver
      metastases, and in 17% of 18 patients with liver metastases. Follow up was
      available for 20 (74%) of 27 patients who had 23 relevant findings. Nineteen
      relevant findings (83%) were confirmed at a median of three (range 0.25-45)
      months of follow up; four (17%) were not confirmed at 30 (range 12-52) months (p
      = 0.025). Findings located in the duodenopancreatic area (90%), chest (100%),
      bone (100%), and liver (60%) were confirmed. Most findings for patients with MEN
      1 involved the chest. CONCLUSION: SRS detects many anomalies susceptible to
      modifying management of patients with ZES, especially in those with sporadic
      disease. The specificity of hot spots located outside the liver seems very high.
      By contrast, the specificity of hot spots located in the liver remains to be
      evaluated when conventional imaging is negative.

PMID- 9274482
TI  - Liver iron concentration and distribution in chronic hepatitis C before and after
      interferon treatment.
AB  - BACKGROUND: Recent studies have suggested that, in patients with chronic
      hepatitis C, elevated iron stores are predictive of a poor response to
      interferon. AIMS: To assess liver iron concentration and distribution before and
      after interferon treatment in patients with hepatitis C in order to evaluate
      further the role of iron in the pathogenesis of hepatitis C. PATIENTS: Fifty-five
      patients with hepatitis C treated with alpha interferon for six months. METHODS:
      Patients were evaluated for liver iron concentration (normal value < 36 mumol/g),
      and liver iron distribution before and six months after therapy. RESULTS: At
      entry: liver iron concentration was elevated in 16/55 patients (29%); iron
      staining (Perls' staining) was found in 31/55 patients (56%) mainly within
      Kupffer and endothelial cells. Iron load was significantly higher in patients
      with the most histological inflammatory activity. Following treatment: liver iron
      concentration decreased significantly (40 (24) to 30 (17) mumol/g, p = 0.001);
      this was related to iron depletion in mesenchymal cells. Iron depletion occurred
      regardless of the response to therapy. Elevated liver iron concentration was not
      found to be a predictive factor of failure of interferon. CONCLUSION: Although
      liver iron stores were usually normal or only slightly elevated in patients with
      chronic hepatitis C, biochemical and histological liver iron content decreased
      following treatment due to the diminution in mesenchymal iron deposits. Iron
      depletion was interpreted as both a consequence of the anti-inflammatory effect
      of treatment and a factor of improvement in liver histology.

PMID- 9274483
TI  - Co-existence of hepatitis A and adult Reye's syndrome.
AB  - Reye's syndrome is most frequently seen in children but has also been described
      in adults. This syndrome is usually associated with ingestion of 5
      aminosalicylates (ASA) or infection with influenza A, influenza B, or varicella
      virus. A case of Reye's syndrome in a 47 year old, previously healthy woman
      precipitated by ingestion of ASA and acute hepatitis A virus infection is
      described. Reye's syndrome was diagnosed on the basis of her clinical course, and
      the presence of hepatic microvesicular steatosis and characteristic electron
      microscopic changes in the hepatocyte mitochondria. The diagnosis of hepatitis A
      was based on higher amino-transferase values than would be expected in Reye's
      syndrome alone, viral serology including the presence of hepatitis A IgM and the
      demonstration of hepatitis A virus RNA on liver biopsy by in situ hybridisation.
      Mitochondrial injury has been demonstrated in acute hepatitis A which, in
      addition to ASA, may have precipitated Reye's syndrome in this patient. The
      association between hepatitis A and Reye's syndrome has not been reported before.
      As hepatitis A virus infection is not sought routinely in patients with Reye's
      syndrome, the frequency of this association is unknown.

PMID- 9274484
TI  - Inhibiting acid and Helicobacter pylori?

PMID- 9274485
TI  - Iron and hepatitis C.

PMID- 9274486
TI  - Treating Helicobacter pylori induced ulcers with antibiotics alone.

PMID- 9274487
TI  - Being toxic to the oesophagus.

PMID- 9274488
TI  - Neurological complications of enteric disease.

PMID- 9274489
TI  - A question of survival.

PMID- 9274490
TI  - Finance ... bad tidings for hospitals in Philadelphia and Pittsburgh.

PMID- 9274491
TI  - Technology. Driven companies.

PMID- 9274493
TI  - Management ... doctors run into trouble when they also try running their
      practices' business planning.

PMID- 9274492
TI  - Conversions ... for-profit conversions are a hot issue for executives.

PMID- 9274494
TI  - HMOs. From red to pink.

PMID- 9274495
TI  - Litigation. Were shareholders sold out?

PMID- 9274497
TI  - Technology. Move over Incredible Hulk.

PMID- 9274498
TI  - Physicians ... primary care doctors are catching up.

PMID- 9274500
TI  - Information ... health care is finally catching up to other technology dependent
      industries in its investment in information systems.

PMID- 9274499
TI  - Long-term care ... home health care meets real needs.

PMID- 9274501
TI  - Technology ... regulations, try holding them in the palm of your hand.

PMID- 9274502
TI  - Mergers/acquisitions ... American Academy of Healthcare Attorneys with the
      National Health Lawyers Association.

PMID- 9274503
TI  - Equipment ... the cost of medical equipment maintenance rose about 80 percent
      from 1989 to 1997.

PMID- 9274504
TI  - Pharmaceuticals ... cutting corners rarely pays.

PMID- 9274505
TI  - The 1997 Hospitals & Health Networks leadership survey.

PMID- 9274506
TI  - Rural routes. For small-town hospitals, nearly all paths lead to this: convert,
      downsize, network.

PMID- 9274507
TI  - From docks to docs. With its acquisition of General Medical, McKesson is offering
      one-stop shopping for drugs and med/surg products. The risks are great--but so
      are the potential rewards from cross-selling.

PMID- 9274508
TI  - Drugs & money. In the high-stakes hunt for blockbuster pharmaceuticals, companies
      are pouring billions each year into R & D--with no guarantee that their products
      will ultimately pass FDA scrutiny.

PMID- 9274509
TI  - Capital spending. Loan program on borrowed time?

PMID- 9274510
TI  - Premiums. 3% ... 5% ... 10% ... Hike!

PMID- 9274511
TI  - Customer service. No room for waiting.

PMID- 9274512
TI  - Insurance reform. These opposites detract.

PMID- 9274513
TI  - Education. Mastering the biz.

PMID- 9274514
TI  - Managed care. Payback time.

PMID- 9274515
TI  - HospitalPulse ... February 1997.

PMID- 9274516
TI  - Acquisitions. Where others fear to tread.

PMID- 9274517
TI  - Prenatal care. Off to a better start.

PMID- 9274518
TI  - Policy. What a difference two years make.

PMID- 9274519
TI  - Apoptosis in autoimmune and non-autoimmune thyroid disease.
AB  - The elimination of autoreactive T cells in the thymus involves the process of
      programmed cell death. Animal model studies, using the lpr and gld strains of
      mice, have identified FAS receptor (FAS) and FAS ligand (FAS-L) as important
      components of this mechanism. Whether FAS and FAS-L are also implicated in the
      autoimmune destruction of a target organ, such as the thyroid, remain
      hypothetical. An accompanying paper in this issue has addressed the question by
      FACS and immunocytochemical analysis of FAS expression and apoptosis in
      thyrocytes grown in culture and in intact thyroid tissues obtained from
      Hashimoto's thyroiditis, multinodular goitre and Graves' disease. The overall
      results suggest that the degree of FAS expression on target cells may determine
      their sensitivity to T-cell mediated cytotoxicity in the absence of perforin or
      granzyme directed apoptosis mechanisms.

PMID- 9274520
TI  - What is Burkitt's lymphoma?
AB  - Burkitt's lymphoma (BL) has been defined on the basis of its characteristic
      cytomorphology. Although histologically identical, endemic BL and sporadic BL are
      distinct clinico-anatomical entities. Their morphological identity probably
      relates to similar chromosomal translocations in both tumours, resulting in c-myc
      de-regulation and consequent unrestrained proliferation without differentiation.
      Similar gene rearrangements are found in a proportion of AIDS-related lymphomas
      that are predominantly extranodal and have the cytomorphology of BL. The term
      "Burkitt-like lymphoma" (BLL) has been applied to a group of high-grade B-cell
      lymphomas that appear morphologically intermediate between BL and
      centroblastic/immunoblastic lymphomas, as detailed in an accompanying paper in
      this issue. These tumours do not usually show c-myc gene rearrangements. The
      association of Burkitt's name with such a disparate group of tumours is confusing
      and new terminology for sporadic BL, AIDS-related BL and BLL is desirable. It is
      important that clinico-anatomical features, as well as cytomorphology, should be
      taken into account in the diagnosis of endemic BL. The origin of a case from
      tropical Africa does not, in itself, imply that it is endemic BL, even more since
      the AIDS epidemic in that continent.

PMID- 9274521
TI  - The interactions of APC, E-cadherin and beta-catenin in tumour development and
      progression.
AB  - Much progress has been made in identifying genes mutated during the development
      of colorectal carcinoma. Mutation of the APC gene in particular appears to be
      fundamental for colorectal tumour initiation. In contrast, loss of expression of
      E-cadherin appears to be a late event, which may be important in the development
      of invasion. Recent clarification of the function of APC, however, has shown that
      it exists in equilibrium with beta-catenin and E-cadherin. This review discusses
      the function of these molecules, their interactions, and how APC mutations may
      alter the equilibrium with beta-catenin and E-cadherin. It is argued that these
      changes cause aberrant architectural development of tissue, which results in loss
      of growth control. It is this escape from growth control, rather than acquisition
      of cell-autonomous growth, which results in the initial development of adenomas.
      The role of the E-cadherin-catenin unit in colorectal tumour invasion is
      discussed and the evidence is reviewed for the involvement of APC and E-cadherin
      in tumours arising from non-intestinal epithelia.

PMID- 9274522
TI  - Analysis of apoptosis in relation to tissue destruction associated with
      Hashimoto's autoimmune thyroiditis.
AB  - The level of apoptosis has been investigated in thyroid tissue from eight
      patients with Graves's disease, one with Hashitoxicosis, three with Hashimoto's
      thyroiditis, and five patients with multinodular goitre, using flow cytometry and
      an in situ immunofluorescence technique. Cryostat sections have also been studied
      for Bcl-2 and APO-1/Fas expression in the thyrocytes and infiltrating
      lymphocytes, to determine their susceptibility to apoptosis. An increased level
      of apoptosis was detected in Hashimoto's glands. This was associated with
      decreased Bcl-2 staining and a patchy APO-1/Fas reactivity on thyrocytes. In
      addition, APO-1/Fas expression was noted within the germinal centres of lymphoid
      follicles. It is suggested that the dysregulation of apoptosis-related genes
      could be an important factor in the progression of destructive thyroid autoimmune
      disease.

PMID- 9274523
TI  - Cellular kinetic and phenotypic heterogeneity in and among Burkitt's and Burkitt
      like lymphomas.
AB  - This study asks whether the known genotypic heterogeneity within and between
      endemic or sporadic Burkitt's lymphomas (eBLs and sBLs, n = 10 each), and Burkitt
      like lymphomas (BLLs, n-12), is reflected in divergent cytokinetics and related
      immunophenotypes. There was strong evidence that eBL and BLL grow markedly faster
      than sBL, as shown by differences in mitotic and apoptotic indices. Furthermore,
      in BLL, the median percentage of neoplastic cells immunoreactive for the bcl-2
      protein was much higher than that observed in eBL and sBL. The reverse was true
      for the median fraction of cells containing c-myc protein. In eBL and sBL, the
      median fraction of bcl-6 protein-positive cells reached values above 50 per cent,
      while cells of 8/12 BLLs did not contain detectable amounts of this protein. This
      observation indicates that in this respect, eBL and sBL resemble normal germinal
      centres of lymphatic tissue much more than do BLL. Evidence for infection of
      neoplastic cells by the Epstein-Barr virus (EBV) was observed in 9/10 cases of
      eBL and in 3/10 of sBL, but not in BLL. EBV-positive lymphomas were associated
      with distinctly lower apoptotic indices and smaller median percentages of bcl-6
      positive cells than EBV-negative tumours.

PMID- 9274524
TI  - Epstein-Barr virus (EBV) infection in infectious mononucleosis: virus latency,
      replication and phenotype of EBV-infected cells.
AB  - Primary Epstein-Barr virus (EBV) infection may manifest itself as a benign
      lymphoproliferative disorder, infections mononucleosis (IM). EBV infection has
      been characterized in lymphoreticular tissues from nine patients with IM using
      the abundantly expressed EBV-encoded nuclear RNAs (EBERs) as a marker of latent
      infection. Expression of the virus-encoded nuclear antigen (EBNA) 2 and of the
      latent membrane protein (LMP) 1 was seen in variable proportions of cells in all
      cases. Double labelling revealed heterogeneous expression patterns of these
      proteins. Thus, in addition to cells revealing phenotypes consistent with
      latencies I (EBNA2-/LMP1-) and III (EBNA2+/LMP1+), cells displaying a latency II
      pattern (EBNA2-/LMP1+) were observed. Cells expressing EBNA2 but not LMP1 were
      also detected; whilst this may represent a transitory phenomenon, the exact
      significance of this observation is at present uncertain. EBER-specific in situ
      hybridization in conjunction with immunohistochemistry revealed expression of the
      EBERs mainly in B-lymphocytes, many of which showed features of plasma cell
      differentiation. By contrast, convincing evidence of latent EBV infection was not
      found in T-cells, epithelial or endothelial cells. Double-labelling
      immunohistochemistry revealed expression of the replication-associated BZLF1
      protein in small lymphoid cells, often showing plasmacytoid differentiation.
      There was no unambiguous expression of this protein in other cell types. These
      results suggest that B-cells are the primary target of EBV infection and that
      plasma cells may be a source of infectious virus found in the saliva of IM
      patients.

PMID- 9274526
TI  - Microsatellite instability in intestinal- and diffuse-type gastric carcinoma.
AB  - To investigate the role of genetic instability in the development of intestinal-
      and diffuse-type gastric cancers, six microsatellite loci were analysed in 98
      carcinomas of the two main histotypes, at both early and advanced stages of
      progression, and in five preneoplastic lesions. RER+ phenotype frequency proved
      to be significantly higher (P = 0.013) in intestinal (23 per cent) than in
      diffuse cancers (5 per cent) and slightly higher in advanced (19 per cent) than
      in early (12 per cent) tumours. When comparing early and advanced tumours of the
      same histotype, a similar frequency was found for diffuse tumours (4 per cent vs.
      6 per cent), and an increase from 19 to 30 per cent for intestinal cancers.
      Instability at more than one locus was limited to intestinal tumours and
      replication errors were also detected in an intestinal dysplasia. On the whole,
      these data suggest that genetic instability has an important and early role in
      gastric carcinogenesis of the intestinal type and a less important role in
      gastric carcinogenesis of the diffuse type. Most tumours of this panel had
      previously been characterized for p53 gene mutations. p53 screening was extended
      to all samples, to investigate the possible association between gene mutations
      and microsatellite instability. Analysis showed a trend (P = 0.07, Fisher's exact
      test) towards a negative association between these two genetic lesions in tumours
      of the intestinal type.

PMID- 9274525
TI  - Cyclin D1 and retinoblastoma gene expression in human breast carcinoma:
      correlation with tumour proliferation and oestrogen receptor status.
AB  - Cyclin D1 (CCND1) and retinoblastoma (Rb) genes are cell cycle regulators which
      are altered in some breast carcinomas. However, the possible cooperation between
      CCND1 and Rb, as well as the influence and coincidence of their abnormalities in
      the proliferative capacity of mammary carcinoma cells in vivo, is still unknown.
      In order to assess both the significance of the CCND1 gene and Rb alterations in
      breast carcinomas and their relationship with the proliferative capacity of the
      tumours and other clinico-pathological factors, CCND1 mRNA expression was studied
      in 46 cases of primary breast carcinomas and matched normal tissue, 45 of which
      were also studied immunohistochemically, Rb expression was analysed in the same
      cases by immunohistochemistry, whereas the proliferative activity of the
      carcinoma was evaluated by flow cytometry. CCND1 mRNA was overexpressed in 19
      tumours (41 per cent). Sixteen cases showed diffuse immunohistochemical
      expression, ten carcinomas had few positive cells, and 19 were absolutely
      negative. CCND1 mRNA and protein overexpression was associated with oestrogen
      receptor (ER) expression by the tumour. Interestingly, lack of ER expression was
      associated with a decreased CCND1 mRNA signal in non-overexpressed tumours. No
      association was observed between CCND1 mRNA or protein overexpression and tumour
      proliferation or other clinico-pathological parameters. Loss of Rb expression was
      observed in 26 per cent of the tumours. This abnormality was significantly
      associated with increased mean S-phase (P = 0.017) and decreased CCND1 mRNA
      expression in non-overexpressed tumours, supporting in vivo the postulated
      regulatory loop between Rb and CCND1 in vitro. We conclude that CCND1 up
      regulation is not associated with increased proliferative activity in breast
      carcinomas, whereas its expression might be regulated in vivo by hormones and Rb.
      Loss of Rb expression is significantly associated with an increased proliferation
      of tumour cells, suggesting an important role in the progression of a subset of
      breast carcinomas, regardless of CCND1 abnormalities.

PMID- 9274527
TI  - Expression of parathyroid hormone-related peptide (PTHrP) in gastric tumours.
AB  - Parathyroid hormone-related peptide (PTHrP) is produced by various neoplasms. It
      has been suggested that it acts as a cytokine for cell proliferation and tumour
      progression. The purpose of this study was to evaluate PTHrP expression in
      gastric cancers by immunohistochemistry. PTHrP was expressed in 71 of 92 (77.2
      per cent) gastric adenocarcinomas without humoral hypercalcaemia. In contrast,
      one case (5 per cent) out of 20 adenomas and none of the background non
      neoplastic epithelium showed PTHrP immunoreactivity. In carcinomas, PTHrP
      immunoreactivity was higher in moderately differentiated adenocarcinomas (21/22;
      95-5 per cent) and poorly differentiated adenocarcinomas (34/34; 100 per cent)
      than in well-differentiated adenocarcinomas (10/23; 43 per cent). Furthermore,
      PTHrP expression was more intense in the deeply invasive portions than in the
      mucosal carcinomas. High percentages of metastatic tumour cells in regional lymph
      nodes were immunopositive. PTHrP mRNA expression was confirmed by in situ
      hybridization in gastric adenocarcinomas. Reverse transcription-polymerase chain
      reaction (RT-PCR) studies of normal gastric mucosa and four human gastric cancer
      cell lines detected PTHrP transcription in NUGC-1 (poorly differentiated) and
      NUGC-3 (poorly differentiated) but not in normal gastric mucosa, MKN-1 (well
      differentiated), and KATO-III (signet ring cell). These findings suggest that
      overexpression of PTHrP may be involved in the malignant transformation and
      progression of gastric carcinomas.

PMID- 9274528
TI  - Overexpression of p53 in normal oral mucosa of oral cancer patients does not
      necessarily predict further malignant disease.
AB  - Recent reports of p53 positivity in the normal mucosa of some head and neck
      cancer patients have been taken as evidence for field cancerization and hence a
      likelihood of the development of further tumours, yet few papers report the
      clinical significance of this finding through long-term follow-up. The
      immunohistochemical detection of p53 expression in clinically and
      histopathologically normal oral mucosa taken from the wound margin following
      excision of oral cancer was assessed using the polyclonal antibody CM1. Fresh
      frozen biopsies of normal oral mucosa and the corresponding tumour from 21 oral
      cancer patients and of normal mucosa from 25 non-cancer patients were assessed
      for p53 overexpression. The 'normal' mucosa was positive in 12 of the oral cancer
      patients and one of the non-cancer patients. Second malignant tumours were seen
      in patients from whom p53-positive 'normals' and p53-negative 'normals' were
      recorded. In five of the p53-positive 'normals', the corresponding cancer was p53
      negative. In one case, where 'normal' mucosa was available from more than one
      site, one region was positive, whilst the other was negative. No obvious
      difference in age, tobacco use, or recurrence rate was seen between positive and
      negative cases. All patients who were still alive were reviewed for a minimum of
      5 years. Using Fisher's exact test, no statistically significant difference was
      found for the rate of second malignant tumours occurring in patients with p53
      positive compared with p53-negative normal mucosa. Thus, the detection of p53 in
      normal mucosa did not necessarily predict a further tumour.

PMID- 9274529
TI  - Distribution of a1(IV) and a3(IV) chains of type IV collagen in lung tumours.
AB  - Tumour invasion is associated with strong remodelling of the extracellular
      matrix, including the basement membrane (BM). The major structural component of
      BMs is type IV collagen, which is composed of an association of three a chains.
      In this study, the distribution of the a1 and a3 chains in both normal and
      neoplastic lung tissues has been examined by immunohistochemistry, using specific
      monoclonal antibodies. In normal tissues, the a1(IV) chain was found in all BMs,
      whereas the a3(IV) chain was only found in alveolar BMs. In 36 lung tumours, the
      a1(IV) chain was detected in all cases, with irregular positivity around tumour
      clusters and in the stroma. It was noteworthy that this stromal distribution was
      particularly associated with the presence of cancer cells, whatever their
      invasive properties. In contrast, in 22 tumours out of 36, the a3(IV) chain was
      only found at the interface between invasive tumour clusters and stroma, with a
      linear and disrupted pattern. These data show a distinctive distribution of type
      IV collagen chains in lung tumours, with expression of a1(IV) chain and likely
      neosynthesis of the a3(IV) chain around some invasive tumour clusters. The
      results suggest the involvement of these BM components in the process of tumour
      invasion.

PMID- 9274530
TI  - Collagen VII expression in human chronic wounds and scars.
AB  - Collagen VII is the major structural component of the anchoring fibrils that
      stabilize the cutaneous basement membrane on the dermis. Disruption and, more
      usually, destruction of the basement membrane are characteristic of wounds that
      are slow, or fail, to heal, such as chronic lower-limb or pressure ulcers. In
      this study, the expression of collagen VII was analysed in 28 human chronic
      cutaneous wounds or scars using a reverse transcription-polymerase chain reaction
      (RT-PCR) technique. Collagen VII expression was detected in 26 of these 28
      cutaneous wounds, but not in two wounds, neither of which showed any clinical
      evidence of healing.

PMID- 9274531
TI  - Nuclear lamin expression in normal testis and testicular germ cell tumours of
      adolescents and adults.
AB  - Nuclear A- and B-type lamins are differentially expressed in tissues, depending
      on the degree of cellular differentiation and proliferative status. By studying
      lamin expression in testis parenchyma and testicular germ cell tumours, further
      insight may be gained into the degree of cellular differentiation in normal
      testis and into the whole spectrum of differentiation lineages found in
      testicular germ cell tumours. Frozen tissue sections of normal testis and the
      different types of testicular germ cell tumours were immunostained with
      monoclonal antibodies to distinct lamin subtypes. Lamin reactivity was evaluated
      in relation to the lineage and degree of cellular differentiation and the
      reactivity patterns were compared with each other and with those in normal
      testis. In normal testis, both A- and B-type lamins were expressed in Sertoli,
      Leydig, and peritubular cells, while in spermatogonia only B-type lamins were
      found and spermatocytes showed weak reactivity with the A-type lamin antibodies.
      Carcinoma in situ was most often positive for both of the B-type lamins and
      negative for the A-type lamins (lamins A and C). In testicular germ cell tumours,
      B-type lamins were always expressed, while A-type lamins were differentially
      expressed. Differentiated non-seminomas were positive for both of the A-type
      lamins, whereas embryonal carcinomas were positive for lamin C and negative for
      lamin A. Seminomas were negative for both of the A-type lamins, with the
      exception of seminomas containing a Ras mutation. Spermatogonia and seminoma
      cells, which follow a differentiation pathway along the spermatogenic lineage and
      show characteristics of germ cells, do not express A-type lamins. Non-seminomas,
      showing embryonal or extraembryonal differentiation, express A-type lamins to
      varying degrees, distinguishing embryonal carcinoma cells from other non
      seminomatous components. This may aid in the evaluation of the percentage of
      embryonal carcinoma in non-seminomatous testicular germ cell tumours as a
      prognostic parameter.

PMID- 9274532
TI  - Microvessel density in core biopsies of prostatic adenocarcinoma: a stage
      predictor?
AB  - Microvessel density was recently reported to be an independent correlate of
      tumour stage in whole mount prostatectomy specimens. This prompted an
      investigation of whether the quantitation of tumour microvessels could also be
      reliably applied to prostatic core biopsies, as a presurgical determinant of
      local tumour extension. The study was performed on a series of 46 unselected
      patients with prostatic adenocarcinomas undergoing radical prostatectomy.
      Intratumoural microvasculature was highlighted immunohistochemically using an
      antibody against CD31 and subsequently evaluated at x 400 magnification in both
      biopsies and corresponding prostatectomies. The highest microvessel count was
      reported for each case. Ten cases (22 per cent) had to be excluded because of
      insufficient measurable tumour areas in core biopsies. The remaining 36 cases (16
      pT2; 20 pT3) showed a high degree of correlation between microvessel density in
      biopsies and prostatectomies (P < 0.0001). Similarly, pre- and post-operatively
      determined microvascular counts correlated well with tumour stage (P < 0.0001).
      Furthermore, the median microvessel density in core biopsies and tumours, i.e.,
      34, distinguished well between organ-confined and organ-extending tumours
      (positive predictive value for pT3 tumours 94.4 per cent; sensitivity 85 per
      cent). These data indicate that the evaluation of microvessels in core biopsies,
      eventually combined with other parameters, could be a reliable method for the
      individual prediction of the post-surgical tumour stage of prostatic
      adenocarcinoma.

PMID- 9274533
TI  - Evaluation of tumour angiogenesis as a prognostic marker in malignant
      mesothelioma.
AB  - Angiogenesis plays an important role in the growth, progression, and metastasis
      of solid tumours. Malignant mesothelioma (MM) of the pleura is a highly invasive
      tumour with a poor prognosis. In the present study, microvascular quantification
      was undertaken on 25 specimens of mesothelioma and 15 specimens of non-neoplastic
      mesothelium (NNM), by staining for the antigens CD34 and CD31. Areas of highest
      intratumoural microvascular density (IMD) were identified and counted either
      manually (mIMD) or on a computerized image analysis system (CIAS; iIMD). The two
      IMDs were significantly correlated with each other (r = 0.736; P < 0.001). The
      average IMD for MM was significantly (P < 0.001) higher than in NNM. Moreover,
      each unit increment in iIMD for MM, when regarded as a continuous variable, was
      significantly (P = 0.001) associated with an increased hazard of about 4 per
      cent. When regarded as a categorical variable, the patients in the highest
      tertile (> 58 vessels/field) had a significantly (P < 0.01; log-rank test)
      shorter survival than patients in the lowest tertile (< 45 vessels/field). This
      association was independent of the age of the patient and of the histological
      type or grade of the MM. No association was noted with p53 immunoexpression.
      Although the mean vascular area of blood vessels measured on the CIAS did not
      correlate with survival, assessment of IMDs can be an important independent
      prognostic indicator in malignant mesothelioma.

PMID- 9274534
TI  - Alterations in cytokeratin expression by the alveolar lining epithelial cells in
      lung tissues from patients with idiopathic pulmonary fibrosis.
AB  - It is generally recognized that epithelial cytokeratins (CKs) are expressed in
      tissue-specific patterns and reflect differentiation, functional specialization,
      and pathological alterations of the cells. Differential epithelial cell types can
      thus be distinguished from each other by their selective expression of particular
      sets of CKs. To determine the characteristics of metaplastic and hyperplastic
      changes of alveolar-lining epithelial cells in the lungs of idiopathic pulmonary
      fibrosis (IPF), the expression of individual CKs was studied
      immunohistochemically using monospecific anti-CK monoclonal antibodies (anti-CKs
      7, 8, 10, 13, 14, 16, 17, 18, 19). Biopsy specimens from 17 patients with IPF and
      normal lung tissues (NL) from seven patients with lung cancer were studied. In
      the IPF specimens, several kinds of altered epithelial cells were observed, which
      showed characteristic changes in CK expression compared with NL, especially CKs
      8, 14, and 17. Hyperplastic type II cells expressed increased CKs 7, 8, and 19,
      but not CK 17; flattened or stratified squamous metaplastic cells expressed
      increased CKs 17 and 14, co-expressed with CKs 7, 8, and 19; bronchiolar
      metaplastic cells expressed increased CKs 7, 8, and 19, co-expressed with CKs 14
      and 17; cuboidal metaplastic cells expressed increased CKs 7, 8, 17, and 19. The
      quantification of individual CKs in the tissues by enzyme-linked immunosorbent
      assay revealed increased expression of CKs 8, 14, and 17 in IPF lung tissues
      compared with NL. These results were consistent with the immunohistochemical
      observations. The hyperplastic and bronchiolar metaplastic phenotypes were
      characterized by their increased expression of simple CKs without CK alteration.
      The squamous metaplastic phenotype showed CK alterations, with the appearance of
      CKs 17 and 14. Epithelial cells are thus altered not only in shape, but possibly
      also in differentiation and function, with potential implications for the
      pathogenesis of IPF.

PMID- 9274535
TI  - Purification and characterization of human nephritogenic antigen that induces
      anti-GBM nephritis in rats.
AB  - Human nephritogenic antigen induces anti-glomerular basement membrane antibody
      glomerulonephritis in rats. This antigen was purified from collagenase
      solubilized renal basement membrane by means of gel filtration and affinity
      chromatography using a rabbit antibody. Western blots of the purified
      nephritogenic antigen using epitope-defined monoclonal antibodies showed that it
      contains the NC1 domains of the a1 to a6 chains of type IV collagen.
      Nephritogenicity was thought to be a feature of the NC1 domains of the a3 to a5
      chains, because the a6 chain is not located in the glomerular basement membrane,
      and because an NC1 fraction consisting of the NC1 domains of the a1 and a2 chains
      was poorly nephritogenic. Autoantibodies in the sera of patients with
      Goodpasture's syndrome were detected by ELISA using the purified nephritogenic
      antigen. These results indicate that the nephritogenic antigen contains the
      Goodpasture antigen, defined as the antigen reactive with sera from patients with
      Goodpasture's syndrome.

PMID- 9274536
TI  - Role of calcium chelation in high-temperature antigen retrieval at different pH
      values.
AB  - Recent work by Shi et al. on the mechanism of high-temperature antigen retrieval
      has claimed that the antigen retrieval process is pH-dependent, with different
      antigens benefitting at high or low pH values of antigen retrieval solutions. It
      has previously been claimed that chelation of Ca2+ at high temperature is an
      essential feature of the antigen retrieval process. In order to resolve this
      apparent dichotomy, the relative antigen retrieval effects were analysed using
      the buffers employed by Shi et al. in both a facilitating and an inhibitory mode.
      The results show that calcium-related effects are optimal at high pH values and
      do not operate at very low pH. The relative antigen retrieval effectiveness of
      hydrochloric acid and its metal halide solutions were also investigated in
      relation to pH. The results of these experiments showed that whilst HCl alone
      produced antigen retrieval (AR), it also produced severe tissue damage, which was
      reduced by the inclusion of inorganic salts. These results suggest that antigen
      retrieval at low pH may be achieved through the dissociation of Ca2+ complexes by
      high concentrations of H+ ions and/or the breaking up of cross-links from
      formalin fixation. Results are also presented to show that chaotropic denaturants
      such as urea and guanidine hydrochloride also function principally through
      calcium chelation, whilst detergents have no role to play in high-temperature
      retrieval.

PMID- 9274537
TI  - A monoclonal antibody pool for routine immunohistochemical detection of human
      respiratory syncytial virus antigens in formalin-fixed, paraffin-embedded tissue.
AB  - Four monoclonal antibodies (MAbs) with specificities for epitopes on human
      respiratory syncytial virus (RSV) proteins preserved after formalin fixation and
      paraffin embedding were identified in fixed and embedded virus-infected HEp-2
      cell pellets. The MAbs bound epitopes on the fusion protein, the nucleoprotein,
      the phosphoprotein, and the M2 protein of the virus. Following high-temperature
      antigen unmasking, immunohistochemical staining revealed RSV antigens in the
      lungs of five of seven children who died with confirmed RSV infection and in none
      of nine children who died for other reasons, with no evidence of RSV infection.
      Staining was cytoplasmic, granular, and confined to epithelial cells. Intense
      staining was seen at the apex of ciliated bronchial and bronchiolar epithelial
      cells in all five positive cases. In one case, of pneumonitis, infected
      pneumocytes were present in the alveoli and in several cases, CD68-positive,
      cytokeratin-negative alveolar macrophages stained for viral antigens. These
      antibodies may prove useful in studies of the pathogenesis of RSV infection.

PMID- 9274538
TI  - Persistently poor pregnancy outcomes in women with insulin dependent diabetes.

PMID- 9274539
TI  - Refugee doctors in Britain: a wasted resource.

PMID- 9274540
TI  - Young adults with arthritic hips.

PMID- 9274541
TI  - Fungal infections in critically ill patients.

PMID- 9274543
TI  - Biggest shake up in higher education for 35 years.

PMID- 9274542
TI  - Medicines information--leaving blind people behind?

PMID- 9274544
TI  - Many chronic pain control treatments are ineffective.

PMID- 9274545
TI  - Outcomes of pregnancy in insulin dependent diabetic women: results of a five year
      population cohort study.
AB  - OBJECTIVE: To monitor pregnancies in women with pre-existent insulin dependent
      diabetes for pregnancy loss, congenital malformations, and fetal growth in a
      geographically defined area of north west England. DESIGN: Population cohort
      study. SETTING: 10 maternity units in Cheshire, Lancashire, and Merseyside which
      had no regional guidelines for the management of pregnancy in diabetic women.
      SUBJECTS: 462 pregnancies in 355 women with insulin dependent diabetes from the
      10 centres over five years (1990-4 inclusive). MAIN OUTCOME MEASURES: Numbers and
      rates of miscarriages, stillbirths, and neonatal and postneonatal deaths;
      prevalence of congenital malformations; birth weight in relation to gestational
      age. RESULTS: Among 462 pregnancies, 351 (76%) resulted in a liveborn infant, 78
      (17%) aborted spontaneously, nine (2%) resulted in stillbirth, and 24 (5%) were
      terminated. Of the terminations, nine were for congenital malformation. The
      stillbirth rate was 25.0/1000 total births (95% confidence interval 8.9 to 41.1)
      compared with a population rate of 5.0/1000, and infant mortality was 19.9/1000
      live births (5.3 to 34.6) compared with 6.8/1000. The prevalence of congenital
      malformations was 94.0/1000 live births (63.5 to 124.5) compared with 9.7/1000 in
      the general population. When corrected for gestational age, mean birth weight in
      the sample was 1.3 standard deviations greater than that of infants of non
      diabetic mothers. Infants with congenital malformations weighed less than those
      without. CONCLUSION: In an unselected population the infants of women with pre
      existent insulin dependent diabetes mellitus have a 10-fold greater risk of a
      congenital malformation and a fivefold greater risk of being stillborn than
      infants in the general population. Further improvements in the management of
      pregnancy in diabetic women are needed if target of the St Vincent declaration of
      1989 is to be met.

PMID- 9274546
TI  - Prospective population based survey of outcome of pregnancy in diabetic women:
      results of the Northern Diabetic Pregnancy Audit, 1994.
AB  - OBJECTIVE: To determine whether the St Vincent declaration (1989) target of
      diabetic pregnancy outcome approximating non-diabetic pregnancy outcome in near
      to being achieved. DESIGN: Prospective collection of population based information
      on pregnancies in women with diabetes from all participating hospitals. SETTING:
      District general and teaching hospitals of the former Northern region. SUBJECTS:
      111 diabetic women booking with pregnancy during 1 January to 31 December 1994.
      MAIN OUTCOME MEASURES: Diabetic control, perinatal mortality rate, fetal
      abnormality rate. RESULTS: The perinatal mortality rate was 48/1000 for diabetic
      pregnancies compared with 8.9/1000 for the background population (odds ratio
      5.38; 95% confidence interval 2.27 to 12.70) and the neonatal mortality rate was
      59/1000 compared with 3.9/1000 (15.0; 6.77 to 33.10). Two late neonatal deaths
      were due to congenital heart defects. Six per cent of all fetal losses (6/109
      cases) were due to major malformations. The congenital malformation rate was
      83/1000 compared with 21.3/1000 (3.76; 2.00 to 7.06) in the background
      population. CONCLUSIONS: Diabetic pregnancy remains a high risk state with
      perinatal mortality and fetal malformation rates much higher than in the
      background population.

PMID- 9274547
TI  - Long-term effect of calcium supplementation during pregnancy on the blood
      pressure of offspring: follow up of a randomised controlled trial.
AB  - OBJECTIVE: To explore the long-term effect of calcium supplementation during
      pregnancy on the offspring's blood pressure during childhood. DESIGN: Follow up
      of a population enrolled in a double blind, randomised, placebo controlled trial.
      SETTING: Perinatal research unit, World Health Organisation's collaborative
      research centre. SUBJECTS: 591 children at a mean age of 7 years whose mothers
      were randomly assigned during pregnancy to receive 2 g/day of elemental calcium
      (n = 298) or placebo (n = 293). MAIN OUTCOME MEASURES: Mean blood pressure and
      rate of high blood pressure of children. RESULTS: Overall, systolic blood
      pressure was lower in the calcium group (mean difference -1.4 mm Hg; 95%
      confidence interval -3.2 to 0.5) than in the placebo group. The effect was found
      predominantly among children whose body mass index at assessment was above the
      median for this population (mean difference in systolic blood pressure -5.8 mm Hg
      (-9.8 mm Hg to -1.7 mm Hg) for children with an index > 17.5 and -3.2 mm Hg (-6.3
      mm Hg to -0.1 mm Hg) for those with an index of > 15.7 to 17.5). The risk of high
      systolic blood pressure was also lower in the calcium group than in the placebo
      group (relative risk 0.59; 0.39 to 0.90) and particularly among children in the
      highest fourth of body mass index (0.43; 0.26 to 0.71). CONCLUSION: Calcium
      supplementation during pregnancy is associated with lower systolic blood pressure
      in the offspring, particularly among overweight children.

PMID- 9274548
TI  - Epidemiology of suicide pacts in England and Wales, 1988-92.
AB  - OBJECTIVE: To describe the epidemiology of suicide pacts in England and Wales
      DESIGN: Analysis of the death certificates and coroners' records of all people
      who died in pacts between 1 January 1988 and 31 December 1992. SUBJECTS: 124
      people who committed suicide in 62 pacts. RESULTS: Suicide in a pact accounted
      for 0.6% of all suicides (124/19721), a rate of 0.6 per million people aged 15
      and over. Forty eight pacts were between married couples and five were between
      family members. The mean age was 56 years. 99 of the 124 subjects were of
      occupational social classes I-III. Poisoning by car exhaust fumes and drugs
      accounted for 116 deaths, with both members of each pair using the same method.
      CONCLUSIONS: Suicide pacts are rare and less common than they were 35 years ago,
      although the epidemiological profile is similar. People who commit suicide in a
      pact are more likely than those who commit suicide alone to be female, older,
      married, and of a high social class.

PMID- 9274550
TI  - Analysis of trends in deaths from accidental drug poisoning in teenagers, 1985
      95.

PMID- 9274549
TI  - Randomised crossover comparison of skin irritation with two transdermal
      oestradiol patches.

PMID- 9274551
TI  - Effect of fundholding on waiting times: database study.
AB  - OBJECTIVES: To determine whether fundholding patients have shorter waiting times
      for surgery than non-fundholding patients and to establish if any such
      differences resulted from practices attaining fundholding status. DESIGN:
      Comparison of waiting times of fundholding and non-fundholding patients for
      elective surgery covered by the fundholding scheme at four providers over four
      years. Comparison of the waiting times for patients of practices in their last
      year outside and first year inside the fundholding scheme with those for patients
      of practices remaining non-fundholding. SETTING: West Sussex. SUBJECTS: Over
      57,000 patients on the elective waiting list who had operations purchased by a
      health authority or fundholding practice during 1992-6. Patients with booked or
      planned elective admissions were excluded. MAIN OUTCOME MEASURES: Waiting times
      for patients of fundholding and non-fundholding patients. RESULTS: Patients of
      fundholding practices had significantly shorter waiting times than those of non
      fundholders for all four providers and over all four years. Waiting times for
      patients did not fall until the year that the practices joined the fundholding
      scheme. CONCLUSIONS: Fundholding shortens waiting times. This may be because
      purchasing of elective surgery is best done at a practice level or because
      fundholding practices are funded overgenerously.

PMID- 9274552
TI  - Managing congenital lacrimal obstruction in general practice.

PMID- 9274553
TI  - ABC of mental health. Addiction and dependence--I: Illicit drugs.

PMID- 9274554
TI  - Should methionine be added to every paracetamol tablet?

PMID- 9274555
TI  - Assessing the methodological quality of published papers.

PMID- 9274556
TI  - Death rates from leukaemia are higher than expected in areas around nuclear sites
      in Berkshire and Oxfordshire.

PMID- 9274557
TI  - MRI scanning to diagnose osteomyelitis in United States and Glasgow. Astute
      clinicians and experienced paediatric radiologists are the essential factors.

PMID- 9274558
TI  - MRI scanning to diagnose osteomyelitis in United States an Glasgow. Children at
      Royal Hospital for Sick Children, Glasgow, have MRI scans if necessary.

PMID- 9274559
TI  - Funding is important for randomised trials of surgery.

PMID- 9274560
TI  - Who is responsible for child mental health? The increasing fragmentation of
      health services for children is the main problem.

PMID- 9274561
TI  - Who is responsible for child mental health? Everyone should work together.

PMID- 9274562
TI  - Who is responsible for child mental health? Too many children are falling through
      the cracks in a confused system.

PMID- 9274563
TI  - Who is responsible for child mental health? People rely on medicine and
      psychiatry to explain the vicissitudes of life.

PMID- 9274564
TI  - Who is responsible for child mental health? Professionals must offer a
      multifaceted approach.

PMID- 9274565
TI  - Who is responsible for child mental health? Attention deficit and hyperactivity
      disorder needs to be recognised.

PMID- 9274566
TI  - Responsibility for services for runaway children must be shared.

PMID- 9274567
TI  - Reducing morbidity from insertion of chest drains. Clamping may be appropriate to
      prevent discomfort and reduce risk of oedema.

PMID- 9274568
TI  - Reducing morbidity from insertion of chest drains. Patients must be disconnected
      from positive airways pressure before insertion of drains.

PMID- 9274569
TI  - Setting target rates for breast feeding would probably be a waste of resources.

PMID- 9274570
TI  - Slutsky effect does not seem to explain circaseptennial rhythm in ear growth.

PMID- 9274571
TI  - Anaesthetists are younger than other doctors.

PMID- 9274572
TI  - Audit of diagnosis and management of hypertension in primary care. Interpractice
      variation in prevalence of hypertension is due to inadequate detection.

PMID- 9274573
TI  - Audit of diagnosis and management of hypertension in primary care. Definition of
      uncontrolled blood pressure used in study is unclear.

PMID- 9274574
TI  - Medical practice is more complicated in remote locations.

PMID- 9274575
TI  - Dengue in the Americas--time to talk.

PMID- 9274576
TI  - Does surgical reduction of heart size reduce heart failure?

PMID- 9274577
TI  - Psychosocial rehabilitation for patients recovering from acute myocardial
      infarction.

PMID- 9274578
TI  - Clinical workup for precocious puberty.

PMID- 9274579
TI  - Health effects due to inhalation of oilseed rape emissions.

PMID- 9274580
TI  - Trinucleotide repeats not the only cause of anticipation.

PMID- 9274581
TI  - Coronary angioplasty versus medical therapy for angina: the second Randomised
      Intervention Treatment of Angina (RITA-2) trial. RITA-2 trial participants.
AB  - BACKGROUND: The role of percutaneous transluminal coronary angioplasty (PTCA) in
      the management of patients with angina remains controversial, particularly in
      patients whose symptoms are adequately controlled by medical treatment. METHODS:
      RITA-2 is a randomised trial comparing the long-term effects of PTCA and
      conservative (medical) care in patients with coronary artery disease considered
      suitable for either treatment option. 1018 patients were recruited from 20
      cardiology centres in UK and Ireland. The 504 randomised to PTCA were intended to
      have dilatation within 3 months. The 514 assigned to medical treatment received
      antianginal drugs; those whose symptoms were not controlled by optimum medical
      therapy could cross-over to myocardial revascularisation. The primary endpoint
      was the combined frequency of death from all causes and definite non-fatal
      myocardial infarction. FINDINGS: This report covers a median 2-7 years' follow
      up. At randomisation 53% of patients had grade 2 or worse angina, and 40% had two
      or more diseased coronary arteries. 93% of patients randomised to PTCA had this
      procedure carried out, within a median of 5 weeks. Death or definite myocardial
      infarction occurred in 32 patients (6.3%) treated with PTCA and in 17 patients
      (3.3%) with medical care (absolute difference 3.0% [95% CI 0.4-5.7%]. p = 0.02).
      This difference was mainly due to one death and seven non-fatal myocardial
      infarctions related to the randomised procedures. There were 18 deaths (11 PTCA,
      seven medical) of which ten were not due to heart disease. Of the patients in the
      PTCA group, 40 (7.9%) required coronary artery bypass grafting (CABG), including
      nine instead of PTCA and seven emergencies following unsuccessful PTCA. 56 other
      PTCA patients (11.1%) required further non-randomised PTCA. In the medical group
      118 patients (23.0%) underwent a revascularisation procedure during follow-up,
      mostly because of worsening symptoms. Angina improved in both groups, but more so
      in the PTCA group. There was a 16.5% absolute excess of grade 2 or worse angina
      in the medical group 3 months after randomisation (p < 0.001), which attenuated
      to 7.6% after 2 years. Total exercise time (Bruce protocol) also improved in both
      groups, again with a treatment difference in favour of PTCA: mean advantage of 35
      s at 3 months (p < 0.001). These benefits of PTCA were greater in patients with
      more severe angina at baseline, judged by high initial grade of angina and short
      initial exercise-time. INTERPRETATION: In patients with coronary artery disease
      considered suitable for either PTCA or medical care, early intervention with PTCA
      was associated with greater symptomatic improvement, especially in patients with
      more severe angina. When managing individuals with angina, clinicians must
      balance these benefits against the small excess hazard associated with PTCA due
      to procedure-related complications.

PMID- 9274582
TI  - Artificial neural networks applied to outcome prediction for colorectal cancer
      patients in separate institutions.
AB  - BACKGROUND: Artificial neural networks are computer programs that can be used to
      discover complex relations within data sets. They permit the recognition of
      patterns in complex biological data sets that cannot be detected with
      conventional linear statistical analysis. One such complex problem is the
      prediction of outcome for individual patients treated for colorectal cancer.
      Predictions of outcome in such patients have traditionally been based on
      population statistics. However, these predictions have little meaning for the
      individual patient. We report the training of neural networks to predict outcome
      for individual patients from one institution and their predictive performance on
      data from a different institution in another region. METHODS: 5-year follow-up
      data from 334 patients treated for colorectal cancer were used to train and
      validate six neural networks designed for the prediction of death within 9, 12,
      15, 18, 21, and 24 months. The previously trained 12-month neural network was
      then applied to 2-year follow-up data from patients from a second institution;
      outcome was concealed. No further training of the neural network was undertaken.
      The network's predictions were compared with those of two consultant colorectal
      surgeons supplied with the same data. FINDINGS: All six neural networks were able
      to achieve overall accuracy greater than 80% for the prediction of death for
      individual patients at institution 1 within 9, 12, 15, 18, 21, and 24 months. The
      mean sensitivity and specificity were 60% and 88%. When the neural network
      trained to predict death within 12 months was applied to data from the second
      institution, overall accuracy of 90% (95% CI 84-96) was achieved, compared with
      the overall accuracy of the colorectal surgeons of 79% (71-87) and 75% (66-84).
      INTERPRETATION: The neural networks were able to predict outcome for individual
      patients with colorectal cancer much more accurately than the currently available
      clinicopathological methods. Once trained on data from one institution, the
      neural networks were able to predict outcome for patients from an unrelated
      institution.

PMID- 9274583
TI  - Randomised trial of home-based psychosocial nursing intervention for patients
      recovering from myocardial infarction.
AB  - BACKGROUND: Increases in life stress have been linked to poor prognosis, after
      myocardial infarction (MI). Previous research suggested that a programme of
      monthly screening for psychological distress, combined with supportive and
      educational home nursing interventions for distressed patients, may improve post
      MI survival among men. Our study assessed this approach for both men and women.
      We aimed to find out whether the programme would reduce 1-year cardiac mortality
      for women and men. METHODS: We carried out a randomised, controlled trial of 1376
      post-MI patients (903 men, 473 women) assigned to the intervention programme (n =
      692) or usual care (n = 684) for 1 year. All patients completed a baseline
      interview that included assessment of depression and anxiety. Survivors were also
      interviewed at 1 year. FINDINGS: The programme had no overall survival impact.
      Preplanned analyses showed higher cardiac (9.4 vs 5.0%, p = 0.064) and all-cause
      mortality (10.3 vs 5.4%, p = 0.051) among women in the intervention group. There
      was no evidence of either benefit or harm among men (cardiac mortality 2.4 vs
      2.5%, p = 0.94; all-cause mortality 3.1 vs 3.1%, p = 0.93). The programme's
      impact on depression and anxiety among survivors was small. INTERPRETATION: Our
      results do not warrant the routine implementation of programmes that involve
      psychological-distress screening and home nursing intervention for patients
      recovering from MI. The poorer overall outcome for women, and the possible
      harmful impact of the intervention on women, underline the need for further
      research and the inclusion of adequate numbers of women in future post-MI trials.

PMID- 9274584
TI  - Randomised placebo-controlled comparison of ivermectin and albendazole alone and
      in combination for Wuchereria bancrofti microfilaraemia in Haitian children.
AB  - BACKGROUND: Lymphatic filariasis and intestinal helminth infections are important
      disorders in tropical areas. Periodic treatment with albendazole is now used in
      many school-based intestinal helminth-control programmes. However, few such
      programmes exist for lymphatic filariasis, despite evidence that single-dose
      treatment with ivermectin can greatly reduce the concentration of Wuchereria
      bancrofti microfilariae in the blood for months to years. We aimed to assess the
      potential for school-based control of lymphatic filariasis by investigating the
      efficacy and tolerability or combined ivermectin and albendazole in Haitian
      schoolchildren. METHODS: In January, 1996, we collected 832 20 microL capillary
      blood samples for inclusion in a randomised controlled study from children aged 5
      11 years, and examined them by microscopy for W bancrofti microfilariae. Infected
      children were randomly assigned treatment with placebo (n = 29), a single 200-400
      micrograms/kg dose of ivermectin (mean, 273 micrograms/kg, n = 28), 400 mg
      albendazole (n = 29), or a combination of 200-400 micrograms/kg ivermectin and
      400 mg albendazole (n = 24). Children with high concentrations of microfilariae
      in the blood were admitted to hospital and adverse reactions were monitored for 3
      5 days, otherwise children were examined at school or during a visit to their
      home. 4 months after treatment, we examined blood samples again for
      microfilariae. FINDINGS: 113 microfilaraemic children were enrolled (mean age 7.8
      years). 4 months after treatment, the proportion of children who remained
      positive for microfilariae was significantly lower in the ivermectin plus
      albendazole group (four [17%]), but there were no significant changes in the
      other three groups (20 [69%] placebo, 22 [76%] albendazole alone, 17 [61%]
      ivermectin alone remained positive; p = 0.004). Geometric mean microfilarial
      concentration decreased from 9.3 to 5.3 per 20 microL blood among children who
      received placebo; from 15.5 to 1.5 per 20 microL blood among those who received
      ivermectin only (p = 0.032); from 14.1 to 5.1 per 20 microL blood among those who
      received albendazole alone; and from 13.7 to 0.3 per 20 microL blood among those
      who received both ivermectin and albendazole (p = 0.0001). Systemic adverse
      reactions did not differ significantly between children who received ivermectin
      alone and those who were treated with ivermectin and albendazole [corrected].
      INTERPRETATION: For children with W bancrofti microfilaraemia, combined treatment
      with ivermectin and albendazole was more effective than treatment with ivermectin
      only, with no measurable increase in severity of adverse reactions.

PMID- 9274585
TI  - Presence of fetal DNA in maternal plasma and serum.
AB  - BACKGROUND: The potential use of plasma and serum for molecular diagnosis has
      generated interest. Tumour DNA has been found in 'the plasma and serum of cancer
      patients, and molecular analysis has been done on this material. We investigated
      the equivalent condition in pregnancy-that is, whether fetal DNA is present in
      maternal plasma and serum. METHODS: We used a rapid-boiling method to extract DNA
      from plasma and serum. DNA from plasma, serum, and nucleated blood cells from 43
      pregnant women underwent a sensitive Y-PCR assay to detect circulating male fetal
      DNA from women bearing male fetuses. FINDINGS: Fetus-derived Y sequences were
      detected in 24 (80%) of the 30 maternal plasma samples, and in 21 (70%) of the 30
      maternal serum samples, from women bearing male fetuses. These results were
      obtained with only 10 microL of the samples. When DNA from nucleated blood cells
      extracted from a similar volume of blood was used, only five (17%) of the 30
      samples gave a positive Y signal. None of the 13 women bearing female fetuses,
      and none of the ten non-pregnant control women, had positive results for plasma,
      serum or nucleated blood cells. INTERPRETATION: Our finding of circulating fetal
      DNA in maternal plasma may have implications for non-invasive prenatal diagnosis,
      and for improving our understanding of the fetomaternal relationship.

PMID- 9274586
TI  - An acutely confused 15-year-old girl.

PMID- 9274588
TI  - Genetic counselling before intracytoplasmic sperm injection.

PMID- 9274587
TI  - Left-ventricular-volume reduction for end-stage heart failure.

PMID- 9274589
TI  - Limbic selectivity of clozapine.

PMID- 9274590
TI  - Treatment of thalassaemia major with phenylbutyrate and hydroxyurea.

PMID- 9274591
TI  - Dead-in-bed syndrome in diabetes mellitus and hypoglycaemic unawareness.

PMID- 9274592
TI  - Viral kinetics in HIV-1 perinatal infection.

PMID- 9274593
TI  - Diffusion changes in status epilepticus.

PMID- 9274594
TI  - Treatment of pemphigus vulgaris with mycophenolate mofetil.

PMID- 9274595
TI  - Osteoarthritis.

PMID- 9274596
TI  - Evidence-based diagnostic radiology.
AB  - The radiological community has a long track record of self-examination, starting
      well before evidence-based medicine came of age. It had to produce such evidence
      to prove the need for and win funds for its expensive gadgets. The assessment of
      new tests is easier than proving the value of well-established ones, and in
      scrutinising the evidence base for an imaging technique a balance must be struck
      between apparent (eg, diagnostic) benefit and real benefit to the patient. And
      even when there is a wealth of good evidence healthy debate continues. So
      radiology may be ahead of some other disciplines in considering the evidence for
      its daily practice. For example, where is the evidence for the routine clinical
      examination-and might the radiologist with a chest X-ray and abdominal ultrasound
      do better?

PMID- 9274597
TI  - Can terathanasia explain the protective effect of folic-acid supplementation on
      birth defects?

PMID- 9274598
TI  - Socioeconomic inequalities in morbidity and mortality in western Europe.

PMID- 9274599
TI  - Socioeconomic inequalities in morbidity and mortality in western Europe.

PMID- 9274600
TI  - Socioeconomic inequalities in morbidity and mortality in western Europe.

PMID- 9274601
TI  - Interpopulation effect of ACE I/D polymorphism on serum concentration of ACE in
      diagnosis of sarcoidosis.

PMID- 9274602
TI  - Citalopram toxicity.

PMID- 9274603
TI  - Digoxin for patients with heart failure in sinus rhythm.

PMID- 9274604
TI  - Digoxin for patients with heart failure in sinus rhythm.

PMID- 9274605
TI  - Adverse event with first-dose perindopril in congestive heart failure.

PMID- 9274606
TI  - Adverse event with first-dose perindopril in congestive heart failure.

PMID- 9274607
TI  - Adverse event with first-dose perindopril in congestive heart failure.

PMID- 9274608
TI  - Adverse event with first-dose perindopril in congestive heart failure.

PMID- 9274609
TI  - Misdiagnosis of multiple sclerosis.

PMID- 9274610
TI  - Magnetic-resonance imaging of the brain of premature infants.

PMID- 9274611
TI  - Health services research.

PMID- 9274612
TI  - Health services research.

PMID- 9274613
TI  - Cancer-registry data in Latvia.

PMID- 9274614
TI  - Population growth.

PMID- 9274615
TI  - Interferon-gamma for respiratory diseases.

PMID- 9274616
TI  - Heart-valve dilator.

PMID- 9274617
TI  - Primary immunodeficiency diseases. Report of a WHO scientific group.

PMID- 9274618
TI  - Can house dust mite-triggered atopic dermatitis be alleviated using acaricides?
AB  - House dust mite (HDM) allergens are the most important triggers for atopic
      dermatitis. Reducing exposure to these allergens may alleviate clinical symptoms.
      Chemicals with acaricidal activity have been used to treat upholstered furniture,
      carpets and bedding with the aim to reduce HDM allergen exposure. These
      chemicals, by reducing HDM, can decrease the concentration of mite allergens in
      dust but improvements in clinical symptoms are not always apparent. Clinical
      improvement is more likely to occur if bedding has been treated rather than
      carpets and upholstery. Future control strategies should be aimed at treating
      bedding. Permethrin is a very efficient killer of mites. It is used topically to
      treat scabies and head lice and is impregnated in bed nets to prevent mosquito
      bites. Even when applied to the skin in high concentrations, it has a very low
      toxicity in humans and other mammals. Permethrin-impregnated bedding may prove to
      be the best control method in the treatment of HDM allergen-triggered atopic
      conditions.

PMID- 9274619
TI  - Distinctive expression of filaggrin and trichohyalin during various pathways of
      epithelial differentiation.
AB  - Filaggrin and trichohyalin are keratin intermediate filament-associated proteins,
      and are primarily expressed in the granular cells of the epidermis and in the
      inner root sheath cells of the hair follicles, respectively. These two proteins
      are, however, occasionally co-expressed in some tissues. To gain more insights
      into the mechanisms for expression and processing of (pro)filaggrin and
      trichohyalin during various pathways of epithelial differentiation, we compared
      their localization by double immunostaining techniques in normal and psoriatic
      epidermis, tongue filiform papillae and cultured human epidermal keratinocytes.
      In normal foreskin, trichohyalin immunoreactive cells were observed only
      occasionally and, when present, they always co-expressed filaggrin. Trichohyalin
      expression occurred, however, in filaggrin-negative cells as well as in filaggrin
      positive cells in the psoriatic epidermis, tongue papillae and cultured
      keratinocytes. Filaggrin and trichohyalin were induced independently at different
      times following calcium shift in cultured keratinocytes. Immunoelectron
      microscopy demonstrated the distinct intracellular distribution of filaggrin and
      trichohyalin. Some filaggrin granules were observed in the cells where
      trichohyalin was diffusely distributed. Likewise some trichohyalin granules were
      found in the cells with diffuse filaggrin labelling. These results suggest the
      existence of distinct expression/processing mechanisms of filaggrin and
      trichohyalin in differentiating keratinocytes.

PMID- 9274620
TI  - Keratinocytes express fibrillin and assemble microfibrils: implications for
      dermal matrix organization.
AB  - Fibrillin-containing microfibrils are key architectural structures of the upper
      dermis and integral components of the dermal elastic fibre network. Microfibril
      bundles intercalate into the dermal-epithelial junction and provide an elastic
      connection between the dermal elastic fibre network and the epidermis.
      Immunohistochemical studies have suggested that they are laid down both at the
      dermal-epithelial junction and in the deep dermis. While dermal fibroblasts are
      responsible for deposition of the elastin and microfibrillar components that
      comprise the elastic fibres of the deep dermis, the cellular origin of the
      microfibril bundles that extrude from the dermal-epithelial junction is not well
      defined. We have used fresh tissues, freshly isolated epidermis and primary human
      and porcine keratinocyte cultures to investigate the possibility that
      keratinocytes are responsible for deposition of these microfibrils. We have shown
      that keratinocytes in vivo and in vitro synthesize both fibrillin-1 and fibrillin
      2, and assemble beaded microfibrils concurrently with expression of basement
      membrane collagen. These observations suggest that keratinocytes co-ordinate the
      secretion, deposition and assembly of these distinct structural elements of the
      dermal matrix, and have important implications for skin remodelling.

PMID- 9274621
TI  - Characterization of LHTric-1, a new monospecific monoclonal antibody to the
      trichocyte keratin Ha1.
AB  - The hair follicle is a heterogeneous tissue involving differentiation of both
      hair forming (trichocyte) and non-hair forming (root sheath) cells; while there
      are many antibody markers available which can determine the distribution of
      'soft' epithelial keratins, fewer have been described which are truly
      monospecific for hair specific 'hard' keratins. We employed the proven strategy
      of raising monoclonal antibodies to a short synthetic peptide from the carboxy
      terminal sequence of mouse Ha1 and report here the successful production of a
      monospecific monoclonal antibody which we have called LHTric-1. We have
      characterized the antibody using immunostaining on rat and human tissues and by
      immunoblotting against an extract of human follicles. The antibody cross-reacted
      between rat and human tissue but did not stain formalin-fixed tissue. LHTric-1
      localized very specifically to the pre-cortical region of the hair follicle in
      early anagen and to pre-cortical cells in the upper bulb in anagen. Telogen
      follicles did not react. LHTric-1 immunoreacted within tongue and nail, staining
      being restricted to the mid-line above the connective tissue core in tongue and
      to the suprabasal layers of the nail matrix. The antibody did not react with the
      fully keratinized hair or nail plate. Finally, in immunoblotting, LHTric-1
      reacted with a single band of 44 kDa, suggesting that a single protein was
      recognized. We conclude that this antibody, by virtue of its known antigen
      sequence specificity, will be useful in research into the formation of hair and
      nail in normal and diseased states.

PMID- 9274622
TI  - Immunohistochemical analysis of tissue remodelling during the anagen-catagen
      transition of the human hair follicle.
AB  - The transition from the growth phase (anagen) to the involution phase (catagen)
      involves profound morphological changes in the human hair follicle. Club hair and
      epithelial column formation, for example, are key features of the catagen phase,
      which result in the disruption of physical interaction between the bulb and the
      dermal papilla. However, the dynamics and tissue remodelling that occur during
      this involution process remain largely unknown. Using monoclonal antibodies
      directed against K14 keratin, trichohyalin, transglutaminase I, desmoglein and
      Ki67 antigen, we followed the movements of each of the main hair follicle
      compartments during the onset of catagen. Our results indicate that the inner
      root sheath is an early target in this process, suggesting a key role for this
      compartment in the maintenance of hair follicle homeostasis.

PMID- 9274623
TI  - Immunohistochemical localization of the Ca2+ binding S100 proteins in normal
      human skin and melanocytic lesions.
AB  - The purpose of this study was to evaluate the expression of the Ca(2+)-binding
      S100 proteins S100A1, S100A2, S100A3, S100A4, S100A6 and S100B in normal skin.
      These immunohistochemical staining patterns were compared with those in
      melanocytic lesions. Paraffin-embedded tissue of normal skin adjacent to 26
      naevi, 39 primary cutaneous melanomas and 14 cutaneous melanoma metastases was
      incubated with polyclonal antibodies against the recombinant human S100 proteins
      (S100A1, S100A2, S100A3, S100A4, S100A6, S100B) using the alkaline phosphatase
      anti-alkaline phosphatase method. The S100A2 antibody stained the basal layer of
      the epidermis and hair follicles of normal skin. Four of 39 primary cutaneous
      melanomas were positive for S100A2, whereas none of the metastases or naevi
      showed any immunoreactivity. The S100A3 antibody only stained the inner root
      sheath cuticle of some hair follicles but no melanocytes or melanocytic lesions.
      Staining of S100A4 was weak and thus omitted to further analysis. S100A6 faintly
      labelled keratinocytes. Langerhans' cells, melanocytes and sweat glands. S100A6
      immunoreaction was found in two of seven junctional naevi, five of seven compound
      naevi, and all dermal and blue naevi. There was an intense cytoplasmatic reaction
      for S100A6 in all primary cutaneous melanomas and in nine of 14 (64%) metastases,
      S100B was positive in melanocytes and Langerhans' cells, all primaries as well as
      in the metastases, S100A1 protein was not detected on any of the tissue specimens
      examined. Whereas S100B and S100A6 antibodies are useful markers for malignant
      melanoma, expression of S100A4 antibody is too low to be used for
      immunohistochemical staining. S100A1 and S100A3 antibodies are not expressed in
      melanocytic lesions and S100A2 is only found in selected tumours. The
      investigated S100 proteins, including S100B and S100A6, are also expressed in
      selected elements of normal skin. These findings are important for correct
      interpretation of staining patterns, when S100 antibodies are used as markers for
      melanoma or other tumours.

PMID- 9274624
TI  - Role of protein kinases in the in vitro differentiation of human epidermal HaCaT
      cells.
AB  - Different chemicals that specifically and selectively inhibit or activate protein
      kinases have been used to define the possible roles of these enzymes in the
      different steps of epidermal differentiation. Using HaCaT keratinocytes as a
      model, and under conditions in which cell proliferation is minimally affected, we
      found that tyrosine kinase inhibition leads to an inhibition of early (spinous;
      keratin k10 expression) and late (granulosum; involucrin expression)
      differentiation processes. cGMP- and cAMP-dependent protein kinases appear to
      modulate the transition from spinous to granular differentiation, a process which
      seems to be negatively controlled by protein phosphatases. Finally, enzymes
      belonging to the protein kinase C family appear to facilitate the transition from
      spinous to granular differentiation programmes while inhibiting the early steps
      of epidermal differentiation.

PMID- 9274625
TI  - Transforming growth factor beta 1 and its latent form binding protein-1 associate
      with elastic fibres in human dermis: accumulation in actinic damage and absence
      in anetoderma.
AB  - Latent transforming growth factor-beta 1 (TGF-beta 1) and its binding protein-1
      (LTBP-1) are components of the extracellular matrix microfibrils of cultured
      human fibroblasts. Using immunohistochemistry we have studied the localization of
      TGF-beta 1 and LTBP-1 and compared their distribution with that of elastic fibres
      in the interstitial connective tissue matrix of the human dermis. Prominent LTBP
      1 specific fibrillar staining co-localized with the elastic fibres in normal
      human skin. Co-distribution was also observed in a number of pathological states
      of the elastic fibres such as solar elastosis, solar keratosis and pseudoxanthoma
      elasticum. TGF-beta 1 had a staining pattern similar to that of LTBP-1 in solar
      elastosis and solar keratosis. No staining for LTBP-1 or TGF-beta 1 was found in
      dermis devoid of elastic fibres, as in anetoderma. LTBP-1 is released from the
      extracellular matrix of cultured human fibroblasts, epithelial and endothelial
      cells by proteases. Analogously, the immunoreactivity for LTBP-1 and TGF-beta 1
      were also lost from the skin sections by elastase, and by trypsin, a protease
      pretreatment commonly used in immunohistochemistry. These results indicate that
      LTBP-1 is a component of the elastin-associated microfibrils of the interstitial
      connective tissue matrix of human skin. Furthermore, the small latent form of TGF
      beta 1 is likely to associate with the extracellular matrix of human dermis via
      LTBP-1. The release of latent TGF-beta 1 from the matrix, as a consequence of
      proteolytic cleavage of LTBP-1, is a plausible extracellular mechanism for the
      regulation of TGF-beta 1 activation.

PMID- 9274626
TI  - The serum levels of sE-selectin are increased in patients with bullous pemphigoid
      or pemphigus vulgaris. Correlation with the number of skin lesions and recovery
      after corsticosteroid therapy.
AB  - Soluble E (sE)-selectin represents the soluble isoform of cellular E-selectin, an
      adhesion molecule synthesized only by endothelial cells. As a consequence, it may
      be considered a marker of endothelial activity. The aim of this study was
      therefore to evaluate the serum levels of sE-selectin in nine patients affected
      with pemphigus vulgaris (PV) and in 15 patients with bullous pemphigold (BP).
      Higher amounts of sE-selectin, median 40.3 ng/mL, range 30-109.6 were found in
      the patients when compared with 20 healthy individuals, median 28.5 ng/mL, range
      6.4-48; P < 0.01, matched for sex and age. These levels were also significantly
      correlated with the number of detectable lesions (r = 0.63, P < 0.001) when the
      patient data were considered at the time of the first observation. Thirteen
      subjects were followed over time for a maximum of 3 months (from three to seven
      observations). During therapy, the number of lesions and the serum sE-selectin
      values decreased concomitantly. Differently from sE-selectin, the serum soluble
      intercellular adhesion molecule-1 (sICAM-1) values were not significantly
      different in the patients from the controls and showed no correlation with the
      serum sE-selectin concentrations or with the number of lesions. The data
      presented point to the possible use of sE-selectin determinations as a non
      specific follow-up marker, suitable to gauge disease intensity over time and
      emphasize that endothelial activation is present in BP as well as in PV.

PMID- 9274627
TI  - Intracellular signalling by binding sites for the antipsoriatic agent
      monomethylfumarate on human granulocytes.
AB  - Monomethylfumarate (MMF), the most active metabolite of the new antipsoriasis
      drug Fumaderm, stimulates an anti-inflammatory mediator profile in human
      leucocytes and inhibits the proliferation of keratinocytes. These effects of MMF
      on cells in vitro may in part explain the beneficial action of Fumaderm in
      patients. In addition, we have reported that MMF stimulates an increase in the
      intracellular free Ca2+ concentration ([Ca2+]i) and the cyclic adenosine
      monophosphate (cAMP) concentration in granulocytes and keratinocytes. Because
      Ca2+ and cAMP control many physiological cellular responses, including cell
      proliferation and inflammatory mediator production, the present study focused on
      the intracellular signal transduction pathway which links interaction between MMF
      and granulocytes with increases in [Ca2+]i and the cAMP concentration. The
      increase in [Ca2+]i in granulocytes after MMF depended both on extracellular Ca2+
      and Ca2+ from intracellular stores. Ca2+ is essential for the increase in the
      cAMP concentration after stimulation with MMF. The results found for
      pharmacological inhibitors of various protein kinases suggest that a
      staurosporine-sensitive protein kinase different from protein kinase C (PKC) and
      protein kinase A is involved in the MMF-induced increase in [Ca2+]i in
      granulocytes. As MMF activated protein tyrosine kinase (PTK), and inhibition of
      this protein kinase partially reduced the increase in [Ca2+]i in granulocytes,
      PTK activity most likely is involved. In addition, activation of protein kinase
      histone 4 (PKH4) probably plays a part in the MMF-stimulated increase in [Ca2+]i
      in granulocytes as well. As MMF stimulated an increase in the GTP-ase activity of
      membranes and pertussis toxin (PTX) inhibited the increase in the [Ca2+]i and
      PKH4 activity of granulocytes stimulated by this compound, it is concluded that
      MMF activates PTX-sensitive G proteins. Competition binding studies with
      radiolabelled dimethylfumarate (DMF) and unlabelled DMF and MMF revealed the
      presence of specific binding sites for methylated fumarates on granulocytes. In
      summary, MMF binds to specific sites on the plasma membrane of cells. This
      interaction activates pertussis toxin-sensitive G proteins which then stimulate
      an increase in PTK and PKH4 activity. These protein kinases may regulate the rise
      in [Ca2+]i and the intracellular cAMP concentration. Elevated [Ca2+]i and
      intracellular cAMP concentration stimulate protein kinases that regulate
      transcription factors. Activation of these factors results in induction of
      downstream gene expression and thus controls cell functions, e.g. cell
      proliferation and production of inflammatory mediators, as has been found for
      cells incubated with MMF.

PMID- 9274628
TI  - Adherence of Candida albicans strains isolated from AIDS patients. Comparison
      with pathogenic yeasts isolated from patients without HIV infection.
AB  - The adherence of yeasts to oral mucous cells is one of the main characteristics
      of the pathogenicity of this fungus. We studied adherence by means of a
      radiometric test to improve the method. We compared a sample of 40 strains of
      Candida albicans isolated from the buccal mucosa of HIV-infected patients with 40
      strains isolated from non-HIV patients. We found that buccally isolated C.
      albicans strains from patients in the initial stages of AIDS adhered to oral
      mucous cells less than the buccally isolated C. albicans strains from subjects
      without HIV infection. Adherence among the strains of HIV patients increased with
      the disease stage until it exceeded that of the normal subjects in proportion to
      the decrease in the CD4/CD8 ratio. The selection of resistant strains by the
      preliminary antifungal treatments gave us a partial explanation for this
      increase. Further research should be carried out to compare these results with
      those obtained from atypical strains and species with high pathogenic potential,
      such as Candida dubliniensis, which is frequently isolated from advanced AIDS, in
      order to prevent systemic infections in these patients.

PMID- 9274630
TI  - Acquired port wine stains: clinical and psychological assessment and response to
      pulsed dye laser therapy.
AB  - Nineteen patients are presented with acquired port wine stains. Acquired port
      wine stains are uncommon vascular lesions with the appearance of a congenital
      port wine stain but onset after birth. This is the largest group of patients
      reported to date. The acquired port wine stain was on the head and neck in 17
      patients and in six this was associated with preceding trauma. Psychological
      assessments in adult patients showed similar morbidity to that seen in patients
      with congenital port wine stains. This morbidity was improved with successful
      laser treatment. Pulsed dye laser therapy resulted in complete clearance of the
      lesion in six (46%) of 13 patients treated. Two further patients had an excellent
      response.

PMID- 9274629
TI  - Calcium homeostasis influences epidermal sweating in patients with vitiligo.
AB  - Patients with vitiligo have a decreased sweating response in both their lesional
      and non-lesional skin (n = 17) compared with healthy age- and sex-matched
      controls (n = 22) after stimulation with the acetylcholine agonist pilocarpine.
      The decreased cholinergic response of the dermal sweat glands in this patient
      group correlates with a significantly lower calcium concentration in sweat
      compared with controls. In addition, a significantly higher potassium
      concentration was found in the pigmented skin of these patients. The other fast
      exchange ions sodium and chloride are unaffected. In vitiligo, there was a
      marginal sweat induction after adrenergic stimulation in four of 10 patients
      tested whereas all controls (n = 10) did not show any response.

PMID- 9274631
TI  - Ultraviolet radiation, melanocytic naevi and their dose-response relationship.
AB  - Melanocytic naevi on the face and neck of 110 Brisbane secondary school students
      aged 16-17 years were mapped according to specified regions to investigate the
      dose-response relationship between ultraviolet (UV) radiation and melanocytic
      naevi. Highest naevus density occurred in regions receiving a mean UV dose of 0.2
      0.4 relative to the vertex while densities were low in minimally and maximally
      exposed regions. This pattern of naevus distribution was unaffected by sex or
      phenotypic features such as skin colour or degree of freckling. These findings
      suggest that there is a narrow dose range over which UV radiation can effectively
      promote the proliferation of melanocytes. A comparison of the regional
      distribution of naevi on the face and neck with that of solar keratoses appearing
      over 1 year on the heads of residents of a neighbouring town has shown them to
      differ significantly. This study may shed some light on the unknown, yet
      expectedly complex, relation of UV radiation to melanocytic naevi.

PMID- 9274632
TI  - Radioiodine-labelled alpha-methyl-tyrosine in malignant melanoma: cell culture
      studies and results in patients.
AB  - Tyrosine is a precursor of melanin synthesis and might thus present a valuable
      marker for melanoma. The aim of this study was to evaluate the uptake of alpha
      methyl-tyrosine (AMT) in melanoma cell cultures and to assess its usefulness as a
      radiopharmaceutical for staging melanoma patients with whole-body scintigraphy.
      Melanoma (M19-cell lines) and fibroblast (negative control) cell cultures were
      incubated with 125I-AMT and the radioactive uptake in the cell lines was measured
      in a gamma-counter over 24 h. For in vivo studies, planar whole-body scintigraphy
      and single photon emission computed tomography (SPECT) of the tumour region was
      performed following injection of 250-350 MBq 123I-AMT in six patients with known
      melanoma metastases. Findings were compared with results of whole-body positron
      emission tomography using 18F-fluorodeoxyglucose (FDG-PET) as a standard of
      reference. Fibroblasts showed an unchanged uptake of (mean +/- SD) 0.56 +/- 0.09%
      15 min and 0.066 +/- 0.09% 24 h, respectively, after incubation of 125I-AMT,
      whereas there was an increased uptake in melanoma cell cultures over time from
      0.9 +/- 0.05% to 7.5 +/- 1.6%. In staging melanoma patients, the sensitivity of
      whole-body AMT-scintigraphy compared with FDG-PET was 37% (10 of 27 metastases).
      AMT is transported and metabolized to a high extent in melanoma cells and 123I
      AMT is accumulated in melanoma metastases. Owing to its low sensitivity, however,
      the clinical use of whole-body AMT scintigraphy cannot be recommended.

PMID- 9274633
TI  - Ultraviolet B radiation was increased at ground level in scotland during a period
      of ozone depletion.
AB  - The potentially harmful effects associated with stratospheric ozone depletion are
      widely acknowledged. As the ozone layer principally absorbs ultraviolet (UV)
      radiation of wavelengths below 290 nm, reductions in stratospheric ozone levels
      are likely to result in increased UVB at the earth's surface, with the risk of
      increased incidence of skin cancer. Measuring the sun's spectrum at ground level
      requires sophisticated and reliable spectral instruments. Results are reported
      for this for the first time in the U.K. using spectral instruments, showing a
      significant increase in short wavelength UV radiation at a time of depleted
      stratospheric ozone. If this trend increases, future ozone depletion could
      contribute to known risks for cutaneous malignancies of all types.

PMID- 9274634
TI  - The influence of sunscreen type on photoprotection.
AB  - Twenty-five volunteers took part in this study whose aims were to determine
      whether there was any difference between the applied amounts of a chemical and
      physical sunscreen of the same sun protection factor (SPF); whether the SPF of a
      chemical sunscreen influenced the quantity applied; and whether individuals who
      burnt easily in sunlight tended to apply more sunscreen than those who tolerated
      sun exposure. We found that most subjects choose to apply about two-thirds the
      quantity of physical compared with chemical sunscreen. This reduction in amount
      applied is likely to lead, in practice, to the physical sunscreen providing a SPF
      of about one-half of that achieved with the chemical sunscreen. In sunscreens in
      which the only variation was the concentration of the active organic chemical
      absorbers (and hence SPF), there was no difference in the amount of sunscreen
      applied and so the protection afforded can be assumed to increase in line with
      the SPF. While there was no statistically significant difference between the
      amounts applied by subjects of different skin types, there was a tendency for
      subjects with the lower skin types to apply more sunscreen than those who burnt
      less easily.

PMID- 9274635
TI  - Treatment of acne with intermittent isotretinoin.
AB  - Adults with acne represent an increasingly important population of acne sufferers
      referred for treatment. Acne, in these patients, is generally mild or moderate in
      severity but tends to be resistant to conventional antibiotic therapy. A study
      was carried out to assess the efficacy of intermittent moderate dose isotretinoin
      as a treatment for acne. Eighty consecutive patients, over the age of 25 years,
      referred with acne unresponsive to, or relapsing rapidly after three or more
      courses of conventional antibiotic therapy were recruited. Acne severity was
      assessed on the face, chest and back using the Leeds grading scale and the number
      of inflamed lesions was counted at the site showing the highest acne grade. The
      patients were 22 men and 58 women. The treatment regimen consisted of
      isotretinoin, 0.5 mg/kg per day for 1 week in every 4 week for a total period of
      6 months. Seventy-five patients completed the study. The therapy was very well
      tolerated with mild cheilitis as the only side-effect. At the end of treatment,
      both total acne grade and lesion counts were significantly reduced (P < 0.0001).
      The acne had resolved in 68 (88%) patients. Twelve months after treatment, acne
      grades and inflamed lesion counts remained significantly improved (P < 0.0001) in
      the 68 patients who responded; however, 26 (39%) patients had relapsed. There was
      a significantly higher incidence of relapse in patients with predominantly
      truncal acne (P = 0.01). Patients who relapsed also had a significantly higher
      total acne grade, lesion count (P < 0.0001) and sebum excretion rate (P < 0.001)
      compared with those whose acne resolved. This study suggests that intermittent
      moderate dose isotretinoin may be a cost-effective alternative to full dose
      isotretinoin in a carefully selected group of adult patients with-acne. Selection
      criteria should include predominantly facial acne, total acne grade less than 1,
      inflamed lesion count less than 20 and sebum excretion rate less than 1.25
      micrograms/cm2 per min.

PMID- 9274636
TI  - Herpetiform pemphigus showing reactivity with pemphigus vulgaris antigen
      (desmoglein 3)
AB  - We report a patient with herpetiform pemphigus (HP) who showed reactivity only
      with pemphigus vulgaris (PV) antigen but not with pemphigus foliaceus (PF)
      antigen. Direct and indirect immunofluorescence revealed keratinocyte cell
      surface staining in the lower layers of the epidermis, where desmoglein 3 (Dsg3)
      is expressed. Immunoblot analysis, using ethylenediamine tetra-acetic acid
      separated human epidermal extracts, revealed that the patient's serum recognized
      only a 130-kDa polypeptide which co-migrated with Dsg3. By antigen-specific
      immunoadsorption studies, using desmoglein 1 (Dsg1) and Dsg3 recombinant protein
      produced by baculovirus expression system, immunoreactivity of the patient's
      serum was completely adsorbed by Dsg3 alone, but not by Dsg1. These results
      indicate that this HP patient produced only anti-Dsg3 autoantibodies and no other
      autoantibodies against components of the keratinocyte cell surface. HP could be a
      variant of PV, in addition to PF, with unique clinical and histological features.

PMID- 9274637
TI  - The scleroatrophic syndrome of Huriez.
AB  - We have examined 14 of 28 members of a four-generation family, 10 of whom
      demonstrated the clinical features of the scleroatrophic syndrome of Huriez, a
      cancer-prone dermatosis. Several members of this family demonstrated additional
      features, previously unrecorded in this syndrome, including poikiloderma-like
      changes on the nose, flexion contractures of the little finger, a distinctive
      little finger nodule, and telangiectasia on the lips. Genetic linkage was
      excluded to distal chromosome 4q (LOD score-4.399 at theta = 0.001). This concurs
      with the recent reappraisal study of one of the two original families described
      by Huriez, in which no evidence of linkage between this syndrome and the MNSs
      erythrocytic system (mapped to 4q28-q31) was found. This is the first report of a
      family from the U.K. with this syndrome.

PMID- 9274638
TI  - Cutis marmorata telangiectatica congenita with hypoplasia of the right iliac and
      femoral veins.
AB  - We describe a 37-year-old woman with an extensive congenital reticulate vascular
      naevus affecting predominantly the right side of the body associated with a
      naevus anaemicus. Investigation of persistent ulceration and scarring of the
      lower legs revealed right-sided hypoplasia of the hemipelvis and underlying
      ipsilateral hypoplasia of the deep veins of the pelvis and leg. This association
      has not previously been reported and its implications for morbidity and
      management are discussed.

PMID- 9274640
TI  - Development of psoriasis after syngeneic bone marrow transplant from psoriatic
      donor: further evidence for adoptive autoimmunity.
AB  - Transfer of donor immunity has been demonstrated in animal models of both
      allogeneic and syngeneic bone marrow transplantation (BMT). Clinical case reports
      have suggested that human autoimmune disease may be similarly transferred.
      However, it is difficult to completely exclude autoimmune phenomena associated
      with graft-versus-host disease (GVHD) as previously reported cases are of
      allogeneic BMT. In addition, the onset of autoimmunity has been distantly related
      to the timing of the transplant, perhaps because of the immunosuppression used
      for prophylaxis and treatment of GVHD. We describe a patient in whom the
      development of psoriasis shortly after receiving syngeneic bone marrow from a
      psoriatic donor and its recurrence with arthropathy following a second syngeneic
      BMT provide more direct evidence for the adoptive transfer of human autoimmune
      disease, probably by T cells.

PMID- 9274639
TI  - Extremely low levels of epidermal skin-derived antileucoproteinase/elafin in a
      patient with impetigo herpetiformis.
AB  - Impetigo herpetiformis (IH) is a rare pustular dermatosis with unknown aetiology,
      typically occurring during pregnancy. Based upon a similar clinical and
      histological presentation, i.e. spongiform accumulation of polymorphonuclear
      leucocytes in the stratum corneum, several authors consider IH as a variant of
      generalized pustular psoriasis (GPP), while others state that IH is a separate
      entity. Skin-derived antileucoproteinase (SKALP) is a strong and specific
      inhibitor of human leucocyte elastase (HLE) and proteinase 3, two neutral
      proteinases that have been implicated in leucocyte migration and tissue
      destruction. Previously, we reported decreased SKALP activity in pustular forms
      of psoriasis compared with plaque psoriasis. In this study we present a case
      study of a patient with IH, where SKALP activity was measured using biochemical
      and immunochemical techniques. Epidermal scales and sera were collected during
      the course of the disease. Comparison was made with three patients with GPP and
      six patients with plaque psoriasis. Initially, anti-HLE activity in epidermal
      scales of the patient with IH was comparable with values in patients with GPP,
      i.e. decreased compared with plaque psoriasis. During the course of the disease,
      anti-elastase activity dropped to undetectable levels, concomitant with the
      appearance of free elastase activity. This finding suggests a total saturation of
      epidermal anti-HLE activity. Low levels of SKALP, presumably complexed with HLE,
      could be measured immunochemically in scale extracts. Serum levels of total SKALP
      correlated with the disease activity. We suggest that a reduced amount of
      epidermal SKALP contributes to an imbalance between elastase and its inhibitor,
      resulting in the formation of epidermal pustules. This mechanism of pustule
      formation could apply both to GPP and IH, suggesting a final common pathway in
      the pathogenic mechanisms of IH and GPP.

PMID- 9274641
TI  - Cellulitis after hip surgery: long-term follow-up of seven cases.
AB  - Cellulitis of the buttock after hip surgery is rarely reported, but raises
      concern about possible infection of the implant. In view of this we have
      investigated the frequency of previous hip surgery in patients with cellulitis of
      the hip and/or buttock and assessed for any predisposing factors. A review was
      made of the case notes of all patients admitted to our department with infectious
      cellulitis of the hip and/or buttock between 1981 and 1995. Seven of nine
      patients previously had had implantation of a hip prosthesis. The interval
      between skin infection and surgery was 7-9 weeks in two patients and 55-520 weeks
      in five. No infection of the implant was evident. The assumed portals of entry
      were gluteal fold intertrigo, tinea pedis, psoriatic plaque and a carbuncle of
      the buttock. The infection was successfully treated by intravenous antibiotics
      and, after a follow-up of a mean 64 months, no recurrence of cellulitis has been
      observed and only one aseptic loosening has occurred. Infectious cellulitis of
      the hip or buttock following hip surgery can occur secondary to impaired
      lymphatic drainage, a few weeks up to several years after surgery, without there
      being any infection of the orthopaedic implant.

PMID- 9274642
TI  - Graft-versus-host disease-like eruption in a patient with non-Hodgkin's lymphoma.
AB  - Graft-versus-host disease (GVHD) is most commonly seen as a complication of bone
      marrow transplantation, although it can occur whenever tissue or blood products
      are given whereby immunologically competent donor lymphocytes react against host
      tissues. A 65-year-old man with non-Hodgkin's lymphoma developed a severe
      widespread erosive eruption of the skin and mucosal surfaces. Clinically and
      histologically it was identical to cutaneous GVHD even though the patient had
      never received tissue or blood products. He failed to respond to conventional
      therapy for GVHD, but his skin improved significantly on treating his underlying
      lymphoma, which eventually proved fatal. There are two previous reports of GVHD
      associated with malignancy but we believe this to be the first case secondary to
      a lymphoma.

PMID- 9274643
TI  - Kaposi's sarcoma associated with immunosuppression for bullous pemphigoid.
AB  - Kaposi's sarcoma may occur in transplant recipients on immunosuppressive
      regimens, but is not well recognized in association with treatment for
      dermatological disease. We report two cases where multifocal Kaposi's sarcoma
      developed following iatrogenic immunosuppression with prednisolone and
      azathioprine for bullous pemphigoid. Both patients were HIV negative and, in one
      case, lesions regressed both clinically and histologically when immunosuppressive
      therapy was withdrawn.

PMID- 9274645
TI  - Subcorneal pustular dermatosis responsive to narrowband (TL-01) UVB phototherapy.

PMID- 9274644
TI  - Prolonged benefit following ultraviolet A phototherapy for solar urticaria.
AB  - Two patients with severe idiopathic solar urticaria, previously resistant to a
      variety of therapies including plasma exchange, benefited from springtime courses
      of ultraviolet A (UVA) monotherapy. Sites which are normally exposed to sunlight
      were treated, in a cabinet fitted with Philips R-UVA lamps (emitting UVA and
      visible wavelengths, with peak at 350 nm), twice daily for 2-3 weeks. One patient
      has been treated in this way for 3, and the other for 2, consecutive years.
      Repeat monochromator phototesting 3 months after their latest courses of UVA
      showed a persistent reduction in severity of abnormal photosensitivity. Both
      patients describe a sustained improvement in their condition lasting over 6
      months after treatment.

PMID- 9274646
TI  - Subcorneal pustular dermatosis (Sneddon-Wilkinson disease) treated with
      narrowband (TL-01) UVB phototherapy.

PMID- 9274647
TI  - A disposable face mask for PUVA and ultraviolet phototherapy.

PMID- 9274648
TI  - Treatment of PUVA itch with capsaicin.

PMID- 9274649
TI  - Electron beam therapy in Arndt-Gottron's scleromyxoedema.

PMID- 9274650
TI  - Successful treatment of epidermolysis bullosa acquisita with mesalazine.

PMID- 9274651
TI  - Cutaneous larva migrans: the case for routine oral treatment.

PMID- 9274652
TI  - Absence of human herpesvirus-8 DNA in angiosarcomas and other skin tumours in
      immunocompetent patients, and in graft-versus-host disease in the
      immunosuppressed recipients of bone marrow transplants.

PMID- 9274653
TI  - Assessment of morbidity from skin diseases.

PMID- 9274654
TI  - Elastosis perforans serpiginosa associated with unilateral atrophoderma of Pasini
      and Pierini in an individual with 47,XYY karyotype.

PMID- 9274655
TI  - Papuloerythroderma of Ofuji and cutaneous T-cell lymphoma.

PMID- 9274656
TI  - Pruritic urticarial papules and plaques of pregnancy in triplet pregnancy.

PMID- 9274657
TI  - Genetics of inherited immunodeficiencies I: X-linked disorders.

PMID- 9274658
TI  - Cleft lip and palate surgery: the need for individual and family counselling.

PMID- 9274659
TI  - Central venous cannulation: how to do it.
AB  - Central venous cannulation is an important clinical tool for the hospital doctor.
      A sound knowledge of applied anatomy, relative contraindications and possible
      complications is required to decrease morbidity and mortality. This article seeks
      to provide the working knowledge required to perform and use central venous
      cannulation safely.

PMID- 9274660
TI  - rhDNase in cystic fibrosis.
AB  - Cystic fibrosis (CF) affects approximately 1 in 2500 live births in the UK
      Caucasian population. Morbidity and mortality closely reflect the degree of
      pulmonary involvement. rhDNase is a new form of therapy in CF care. Phase 1, 2
      and 3 trials have shown it to be well-tolerated, with patients showing initial
      increases in respiratory function of around 13% from baseline. A years
      prescription costs $7500. This review discusses our views on how this expensive
      new therapy can best be used.

PMID- 9274661
TI  - Diagnosis of functional neurological disease.
AB  - Functional disease is a common and difficult problem in clinical neurology. A
      thorough appraisal should be undertaken before concluding that a patient's
      problem is not physically based. This article describes symptoms and signs of
      potential value in the diagnosis of such disorder.

PMID- 9274662
TI  - Acute colonic pseudo-obstruction in the obstetric patient.

PMID- 9274663
TI  - Immunosuppressive treatment in asthma.

PMID- 9274664
TI  - Classification and management of brittle asthma.

PMID- 9274665
TI  - Leg lengthening and bone transport in children.
AB  - It is now possible to reliably lengthen limbs for inequality or short stature by
      distraction osteogenesis using external fixators. Similar techniques offer new
      methods of treating infected fractures and non-unions and correcting soft tissue
      contractures and bony deformities. This article outlines the techniques and
      indications for leg lengthening and bone transport.

PMID- 9274666
TI  - Gemcitabine.
AB  - There is widespread consensus that a plateau has been reached in the
      effectiveness of known DNA interactive drugs against most malignancies.
      Combination treatments, dose intensification and schedule alterations (e.g.
      infusional and neoadjuvant treatments) represent exciting research opportunities
      and possibly the means for making meaningful progress. However, frustration with
      the slow pace of even these most novel approaches has led to a search for newer
      drug targets and great expectations of new drugs.

PMID- 9274667
TI  - Animal models in biomedical research: transgenesis and gene targeting.

PMID- 9274668
TI  - Skill mix in clinical radiology.

PMID- 9274669
TI  - Skill mix in radiology.

PMID- 9274671
TI  - Cleft lip and palate surgery: family counselling.

PMID- 9274670
TI  - Cleft lip and palate surgery: family counselling.

PMID- 9274672
TI  - AIDS in Africa: face the facts.

PMID- 9274673
TI  - Intensive therapy of acute stroke.

PMID- 9274674
TI  - Genetics of inherited immunodeficiencies II: autosomal recessive disorders.

PMID- 9274675
TI  - Survey of use of thromboprophylaxis for routine total hip replacement by British
      orthopaedic surgeons.
AB  - This study looked at current use of thromboprophylaxis for routine total hip
      replacement surgery among British orthopaedic surgeons. Of those who replied to a
      postal survey, 85% use chemical prophylaxis, 15% used mechanical prophylaxis and
      only 1% use no prophylaxis. This showed a significant increase in the number of
      surgeons using chemical prophylaxis, particularly low molecular weight heparin,
      compared to a similar survey in 1989.

PMID- 9274676
TI  - Insertion of a pulmonary artery flotation catheter: how to do it.
AB  - This article outlines a safe and successful technique of inserting the pulmonary
      artery catheter. Readers should regard it as a supplement, not a substitute, to
      bedside instruction by an experienced and competent clinician.

PMID- 9274677
TI  - Interferon alfa-2a.
AB  - Interferon alfa-2a shows both antiviral and antitumoral activity, but its role in
      the treatment of many conditions remains controversial. It is, however, the
      treatment of choice for chronic, active hepatitis B, chronic hepatitis C and AIDS
      related Kaposi's sarcoma, and is also effective in metastatic renal carcinoma and
      chronic myelogenous leukaemia. Optimal dose regimens are unclear, and further
      randomized trials are needed.

PMID- 9274679
TI  - The police and Criminal Evidence Act (PACE) and confessions.

PMID- 9274678
TI  - Body temperature control and anaesthesia.

PMID- 9274680
TI  - Psychopathology of sexual offenders.

PMID- 9274681
TI  - Risk assessment in schizophrenia.

PMID- 9274682
TI  - Intent.

PMID- 9274683
TI  - Alcohol and the heart.
AB  - Alcohol consumption is the norm in the UK population. Although there is strong
      evidence that a moderate alcohol intake is protective against coronary heart
      disease, alcohol has other potentially harmful effects on the cardiovascular
      system. Alcohol may raise blood pressure, damage the myocardium, precipitate
      arrhythmias and damage the developing fetal heart.

PMID- 9274684
TI  - B-complex vitamins in the prophylaxis and treatment of Wernicke-Korsakoff
      syndrome.
AB  - Wernicke-Korsakoff syndrome, which is associated with high morbidity and
      mortality, is a more common neuropsychiatric sequela of alcohol misuse than is
      widely realized. It is easily prevented and treated with parenteral B-complex
      vitamins, although this treatment is widely under-utilized.

PMID- 9274685
TI  - 'Xtra' contractual referrals.
AB  - This article will consider key issues of extra contractual referral (ECR)
      management primarily from a purchaser's perspective. What ECRs are, why their
      management is a vital concern for the NHS and what actions are necessary to
      ensure priority setting is not distorted will be briefly addressed.

PMID- 9274687
TI  - The Pensions Act: what does it all mean?

PMID- 9274686
TI  - Pneumatosis cystoides intestinalis in a case of sigmoid volvulus.

PMID- 9274688
TI  - Hernia today.

PMID- 9274689
TI  - Providing a vascular service.

PMID- 9274691
TI  - Antibiotic resistance.

PMID- 9274692
TI  - Management training for junior doctors.

PMID- 9274693
TI  - Heterogeneity of nuclear DNA pattern and its relationship with cell cycle
      activity parameters in multinodular goitre.
AB  - OBJECTIVE: Recent studies suggest that the malignancy rate in multinodular goitre
      is not significantly different from that observed in solitary nodules and that
      chromosomal aberrations are not infrequent in multinodular goitre. To further
      investigate this topic we determined the DNA pattern in multinodular goitres.
      DESIGN: DNA ploidy and cell cycle activity parameters were determined in
      multinodular goitres. PATIENTS: We evaluated 235 patients (185 female, 50 male,
      mean age 52 +/- 13 years), who had undergone thyroidectomy; 11 of them harboured
      occult differentiated microcarcinoma. MEASUREMENTS: DNA index (DI), coefficient
      of variation of G0/G1 phase (CV), percentage of cells in S phase (%S) and in G2+M
      phase (%G2-M) and proliferative index (PI = %S+%G2-M) were determined by flow
      cytometric analysis (FCM) in tissue samples taken from 3 different areas of the
      thyroid gland. RESULTS: Aneuploid DNA was found in 50 goitres without carcinoma
      (22.3%) and in 5 goitres with carcinoma (45.5%). The mean PI of euploid cells in
      the goitre without carcinoma was significantly higher in the goitres with an
      aneuploid component compared to the goitres without aneuploidy (10.8 +/- 1.3 SEM
      vs 6 +/- 0.32; P +/- 0.001). Also, the percentage difference between maximal and
      minimal PI found within each goitre (delta PI %) was higher in the former group
      (373 +/- 49 SEM vs 142 +/- 11.3; P < 0.0001). The PI was significantly higher in
      goitres with carcinoma compared to the goitres without carcinoma (12.9 +/- 3.2
      SEM vs 7.07 +/- 0.40; P < 0.05). CONCLUSIONS: The findings of increased
      proliferation rate in goitres with an aneuploid or neoplastic component suggests
      that some factors involved in goitrogenesis could also be responsible for the
      development of chromosomal aberrations and/or for the selection of cellular
      clones endowed with high growth potential.

PMID- 9274694
TI  - Hyperproliferation and aneuploidy in multinodular goitre and thyroid follicular
      neoplasia: causal or incidental relationship?

PMID- 9274695
TI  - Pituitary tumours presenting in the elderly: management and outcome.
AB  - OBJECTIVE: In elderly patients there are few data on the efficacy and safety of
      pituitary surgery and radiotherapy (DXT). The aim of the present study was to
      assess the mode of presentation, treatment and outcome of patients > 64 years
      with a pituitary tumour presenting to a regional neuroendocrine service. DESIGN:
      A retrospective case note review of all patients with a pituitary tumour, from
      1986 to 1993, was performed with DXT information from computerized records.
      PATIENTS: Forty-four patients were identified: median age 70 (65-83) years; 25
      males; followed for a mean of 34 (range 0-84) months. RESULTS: The commonest
      presenting symptom was with visual disturbance (24 patients) with a further 9
      with asymptomatic visual field defects. Five patients had acromegaly and two
      prolactinoma. Thirty-two patients underwent transsphenoidal surgery (TSS) (with
      post-operative DXT in 14 cases) and 6 craniotomy. Two patients had DXT as the
      primary procedure and four were observed. Visual fields improved in 21 of 29
      patients. Perioperative complications occurred significantly more often after
      craniotomy (5/6) than after TSS (6/32) (P < 0.01). Eight patients died during the
      follow-up period (three deaths tumour related; one death followed DXT).
      CONCLUSIONS: Pituitary adenoma is a remediable cause of visual disturbance in the
      elderly. Most tumours were non-functioning. Age alone is not a contraindication
      to active treatment particularly with transsphenoidal surgery and radiotherapy.

PMID- 9274696
TI  - Effect of desmopressin on ACTH and cortisol secretion in states of ACTH excess.
AB  - OBJECTIVE: To assess the ability of desmopressin administration to stimulate
      ACTH/cortisol secretion in patients with Cushing's disease, either before or
      after surgery, and in patients with other states characterized by ACTH
      hypersecretion, and to compare the results with those obtained after CRH testing.
      DESIGN AND SUBJECTS: Plasma ACTH and serum cortisol levels were evaluated after
      the administration of desmopressin (10 micrograms i.v.), CRH (1 microgram/kg
      i.v.) and saline on different days in 17 patients with Cushing's disease, 1 with
      occult ectopic ACTH syndrome, 5 with Addison's disease, 3 who had been
      bilaterally adrenalectomized for Cushing's syndrome and 4 normal subjects. After
      pituitary adenomectomy desmopressin and CRH were administered again to 13 of the
      patients who had undergone pituitary surgery for their Cushing's disease.
      RESULTS: In 16 patients with Cushing's disease with microadenoma a positive
      ACTH/cortisol rise occurred in 11 patients after both desmopressin and CRH, 2
      other patients were responsive only to desmopressin and 2 only to CRH, while in 1
      patient equivocal responses to both tests were found. The persistence of a
      hormonal response to desmopressin after pituitary adenomectomy for Cushing's
      disease correlated with unsuccessful surgery, while, contrary to CRH, absent
      ACTH/cortisol rises were found in cured patients 1 and 12 months after operation.
      In 1 patient suspected for ectopic ACTH hypersecretion, desmopressin and CRH
      administration did not cause any ACTH/cortisol rise. Significant ACTH rises
      occurred after both desmopressin and CRH testing in patients with Addison's
      disease. All the 3 patients adrenalectomized for Cushing's syndrome showed a rise
      of ACTH levels after CRH, while a similar response after desmopressin occurred in
      only one of them. CONCLUSIONS: Desmopressin is able to stimulate ACTH and hence
      cortisol release in Cushing's disease. It may be a useful test in patients with
      doubtful responses to CRH test, in those exhibiting responses to CRH
      indistinguishable from those of normal subjects and in the postoperative follow
      up of Cushing's disease. In some patients with abolished or reduced cortisol feed
      back at hypothalamic-pituitary level the sensitivity of normal corticotrophs to
      desmopressin is enhanced.

PMID- 9274697
TI  - Clinico-pathological study of Cushing's disease with large pituitary adenoma.
AB  - OBJECTIVE: To explore the biological and morphological differences between large
      Cushing's adenomas and small adenomas, we investigated the clinical,
      endocrinological, neuroradiological, and histological features of patients with
      large Cushing's adenomas and compared them with patients with small Cushing's
      adenomas. PATIENTS: Five of 250 patients with Cushing's disease undergoing trans
      sphenoidal operations from 1989 to 1995 had large adenomas with maximum diameters
      greater than 30 mm. The clinical characteristics of these five patients were
      compared with the 14 patients with Cushing's disease with small adenomas in our
      series. RESULTS: Oedema, myopathy, and mental disturbance were more frequent and
      hypertension was less frequent among patients with large adenomas. The high-dose
      (8 mg) dexamethasone test did not suppress cortisol production in any of the five
      patients. Invasion into surrounding tissue was demonstrated by magnetic resonance
      imaging in all five cases. All five large adenomas had scarce or no periodic acid
      Schiff-positive granules and were sparsely granulated ultrastructurally. Three
      tumours contained cells with honeycomb Golgi apparatus which rarely contained
      immature secretory granules. One Crooke's cell adenoma contained trapped or
      displaced secretory granules. The other tumour had dilated trans-Golgi network
      derived vacuoles that contained reticular or circular electron-dense material.
      These findings were in striking contrast to those of small Cushing's adenomas,
      which showed strong PAS positivity, densely-packed granulation, and had prominent
      Golgi complex harbouring developing secretory granules. CONCLUSIONS: We found
      that the tumour cells in large adenomas produced only small amounts of ACTH, and
      showed indications of disturbances in the regulated exocytotic pathways. These
      factors may account for the different clinical characteristics of Cushing's
      disease with large pituitary adenomas.

PMID- 9274698
TI  - Impaired reproductive function in women treated for growth hormone deficiency
      during childhood.
AB  - OBJECTIVE: There are limited data which suggest that disturbance of reproductive
      function may occur in GH-deficient women. We have evaluated the consequences of
      growth hormone (GH) deficiency on reproductive function in women treated for GH
      deficiency during childhood. DESIGN: Questionnaires were sent to 73 GH-deficient
      women who had been treated for GH deficiency during childhood. The response rate
      was 82%. These 60 women were then visited to obtain further information
      concerning their reproductive status. During these visits, blood samples were
      obtained from 39 women, to evaluate their hormonal status, and 29 of them had a
      standard insulin tolerance test (ITT), as part of an adult GH substitution trial.
      Paediatric and gynaecological records were evaluated in all 60 women. SUBJECTS:
      Sixty GH-deficient women treated in childhood for this deficiency were included
      in the study. The median age at follow up was 27 years (range 20-43). GH
      treatment had been discontinued for 9 years (range 2-26). MEASUREMENTS: In the
      questionnaire and during the visit, attention was paid to GH treatment, pubertal
      development, menstrual cycle disturbances and fertility. In the 39 blood samples
      IGF-1, IGFBP-3, TSH, T4 and T3 were measured. GH responses were measured by a
      standard ITT. RESULTS: Thirty-four women showed no spontaneous pubertal
      development. Of the 26 women who did, menarche occurred in 39% at the age of 16
      years or older. At the time of the study, menstrual cycles in these 26 women were
      as follows: 12 had regular menstrual cycles, three had developed secondary
      amenorrhoea after discontinuation of GH treatment, five had irregular menstrual
      cycles and six had oligomenorrhoea. The 34 women with disturbed pubertal
      development and the three with secondary amenorrhoea were infertile because of
      hypogonadotrophism. Only 13 out of 60 women desired pregnancy or had been
      pregnant. Three with regular menstrual cycles had primary infertility. Ten had
      ovulation induced or IVF. Six of these became pregnant after 1-7 cycles. Three
      were still under treatment, the duration of their treatment varying from 3 to 7
      years. One woman discontinued treatment. At the time of the study, nine women had
      actually conceived. Five out of ten completed pregnancies resulted in Caesarian
      sections because of cephalo-pelvic disproportion or arrest of labour. During the
      ITT three of 29 women showed GH responses exceeding 5 micrograms/l (10 mU/l),
      ruling out complete GH deficiency. Higher GH peaks (NS), IGF-1 (P , 0.01) and
      IGFBP-3 (P < 0.01) levels were found in women with regular menstrual cycles,
      compared to women using sex-steroid substitution and amenorrhoeic women.
      CONCLUSIONS: From this study, it can be concluded that disturbances in
      reproductive function can be expected in women treated for GH deficiency during
      childhood, so it is advisable to inform these women of this possibility and to
      maintain follow-up after discontinuation of GH treatment. Whether the
      somatotrophic axis exerts a direct effect on ovarian function or whether more
      severe GH deficiency is more frequently accompanied by disturbances in
      gonadotrophin secretion still has to be elucidated.

PMID- 9274699
TI  - Pituitary size and function in children and adolescents with shunted
      hydrocephalus.
AB  - OBJECTIVE: Most previous reports of endocrine disorders in children with shunted
      hydrocephalus have been case reports and there is a lack of systematic
      information on pituitary anatomy and function among these children. We have
      obtained these data in a large group of individuals with shunted hydrocephalus.
      DESIGN: A controlled cross-sectional study. PATIENTS: Fifty-four children and
      adolescents with shunted hydrocephalus were studied for pituitary anatomy and
      function. They had 54 age- and sex-matched controls (group I). The mean age of
      the patients and controls was 12.6 years and the mean shunting period 10.6 years.
      There was a second control group (II) for the magnetic resonance imaging (MRI)
      and a third control group (III) for the radiography of the sella turcica.
      MEASUREMENTS: The anatomy was visualized by MRI of the pituitary gland and by
      radiography of the sella turcica. The functional evaluation included an arginine
      insulin test and a combined stimulation test with corticotrophin releasing factor
      (CRF), GnRH and TRH. RESULTS: The patients were shorter (height 148.4 cm vs 153.7
      cm, P < 0.05 and relative height -0.5 SDS vs 0.4 SDS, P < 0.05) and had a higher
      BMI than the control group I (20.6 kg/m2 vs 18.0 kg/m2, P < 0.001). They had also
      a greater pituitary height than the control group II (5.8 mm vs 5.1 mm, P <
      0.01). The patients had significantly lower basal GH levels (P < 0.001) than
      controls I. Sixteen patients (30%) had a poor GH response (< 20 mU/l) in the
      arginine-insulin test. Pituitary height was significantly lower among these
      patients than in those with a normal response (4.7 mm vs 6.3 mm, P < 0.01), who
      had an increased pituitary height compared to controls II (5.1 mm, P < 0.01). The
      area under the curve (AUC) for GH correlated with the pituitary volume (r = 0.50,
      P < 0.001). The patients had higher basal FSH and LH concentrations than controls
      I (P < 0.001). The peak to basal ratios of FSH and LH were increased in the
      prepubertal patients and that of LH at Tanner pubertal stage II in the females.
      The basal FSH and LH levels correlated with the pituitary volume (r = 0.50 and r
      = 0.54, P < 0.001 for), as did FSH AUC and LH AUC (r = 0.48 and r = 0.75, P <
      0.001 for both). CONCLUSIONS: These observations indicate that children with
      shunted hydrocephalus have an increased pituitary size on average. About one
      third of these patients had signs of reduced GH secretion and significantly lower
      pituitary height, which probably contributes to their poor linear growth.
      Increased pituitary size was associated with enhanced gonadotrophin secretion,
      which may result in early puberty in children with shunted hydrocephalus.

PMID- 9274700
TI  - Growth deficiency in polytransfused beta-thalassaemia patients is not growth
      hormone dependent.
AB  - OBJECTIVE: Growth deficiency is commonly seen in polytransfused beta-thalassaemia
      patients, especially in adolescence. It is not completely dependent on the lack
      of their pubertal growth spurt. GH impairment at different levels (hypothalamic
      or pituitary) and/or a reduced IGF-1 synthesis have been suggested the main
      causes of stunted growth in these patients. We evaluated the relationship between
      GH reserve and growth in short beta-thalassaemia patients. PATIENTS: Twenty-nine
      short patients (height < -1.8 SDS for chronological age) were divided into two
      groups (low and normal responders) on the basis of their GH peak during insulin
      and clonidine tests (< or = and > 20 mU/l, respectively). All but one low
      responders underwent the GHRH test to exclude the impairment of somatotroph
      function and in eight of them an IGF-1 generation test was also performed. The
      two groups were compared with each other with respect to growth (height
      deficiency, height velocity, bone age and bone delay), haematological
      characteristics (serum ferritin levels, age at the start both of low
      (subcutaneous) s.c. infusion of desferrioxamine and of transfusional therapy) and
      serum IGF-1 and IGF-1 binding protein 3 levels. RESULTS: Thirteen patients (45%)
      (11 males, two females) were low responders, all but two having serum IGF-1 < 5th
      centile (< 0.1 centile in 42%); the GHRH test excluded the impairment of
      somatotroph function in 8/12. Height deficiency, serum ferritin levels, and age
      at the start of s.c. chelating therapy did not differ in low compared to normal
      responders. Height was negatively correlated both with the age at the start of
      s.c. chelating therapy and with serum ferritin levels. CONCLUSION: The reduction
      of GH reserve, more frequently due to a hypothalamic than to a pituitary
      dysfunction, is frequent in polytransfused beta-thalassaemia patients, especially
      in males. The height function is not related to the GH reserve, given the current
      methods for testing GH reserve. Late start of s.c. chelating therapy as well as
      haemosiderosis seem to play a role in the height deficiency, but not in GH
      reserve. Impairment of GH secretory reserve, therefore, cannot be considered the
      main cause of height deficiency in these patients.

PMID- 9274702
TI  - Different effects of growth hormone releasing peptide (GHRP-6) and GH-releasing
      hormone on GH release in endogenous and exogenous hypercortisolism.
AB  - OBJECTIVE: Chronic hypercortisolism is associated with decreased GH
      responsiveness to GHRH. GHRP-6 is a synthetic hexapeptide that releases GH in
      several species, including man. As GHRH and GHRP-6 apparently stimulate GH
      release by different mechanisms, we evaluated the GH responses to these peptides
      in patients with endogenous and exogenous glucocorticoid excess and also in
      control subjects. DESIGN: Six patients with endogenous hypercortisolism, nine
      with exogenous glucocorticoid excess and 10 normal controls were submitted to
      three tests, in random order, with GHRH (100 micrograms), GHRP-6 (1 microgram/
      kg) or GHRP+GHRP-6, in the same doses, i.v., on separate days. MEASUREMENTS: GH
      was measured by immunofluorometric assay. IGF-I was determined by
      radioimmunoassay. Plasma glucose was measured by the glucose-oxidase technique.
      RESULTS: Peak GH values (mean +/- SE; microgram/l) after GHRH were significantly
      blunted in endogenous (2.0 +/- 0.7) and exogenous (3.6 +/- 1.2)
      hypercortisolaemic patients compared to controls (24.9 +/- 6.1). The endogenous
      group had lower peak GH values after GHRP-6 alone (7.7 +/- 1.9) or together with
      GHRH (18.8 +/- 5.8) than those observed in controls (GHRP-6: 22.1 +/- 3.6;
      GHRH+GHRP-6: 77.4 +/- 15.0) and in exogenous hypercortisolism (27.4 +/- 6.2 and
      78.1 +/- 19.9). There were no differences in the GH responses to GHRP-6 alone or
      in combination with GHRH when controls were compared to the exogenous group. No
      changes in plasma IGF-I and glucose levels were observed. CONCLUSIONS: Our
      results suggest that hypercortisolism had a different effect on the GH-releasing
      mechanisms stimulated by GHRH and GHRP-6. Moreover, in endogenous
      hypercortisolism both GHRH and GHRP-6 pathways are affected, while in the
      exogenous group GHRP-6 releasing mechanisms are apparently preserved.

PMID- 9274701
TI  - Altered bioavailability due to changes in the formulation of a commercial
      preparation of levothyroxine in patients with differentiated thyroid carcinoma.
AB  - OBJECTIVES: In July 1995 we began noticing an unusually high rate of elevated TSH
      levels in patients with differentiated thyroid cancer treated with levothyroxine
      specifically the brand Levothroid-becoming more obvious from September 1995.
      Faced with the possibility that these findings had some relationship to the drug
      taken, we carried out a prospective study, changing this brand of levothyroxine
      for another. DESIGN AND PATIENTS: We studied 58 patients with differentiated
      thyroid carcinoma (50 women and eight men; aged 22-75 years) who were being
      treated with levothyroxine and who had previously had adequate TSH suppression.
      Their Levothroid tablets were changed to the same dose of Dexnon tablets, and
      their clinical and analytical response was evaluated 2 months later. The patients
      were divided into two groups according to their TSH level at the start of the
      study: group 1, 42 patients with TSH > 0.2 mU/l (not suppressed) and group 2, 16
      patients with TSH < or = 0.2 mU/l (suppressed). RESULTS: After 2 months with
      Dexnon the TSH levels in group 1 fell significantly (P < 0.0001) also decreasing
      in group (P < 0.09). The free T4 and free T3 rose significantly in both groups.
      After the change to Dexnon, 17 patients (40%) in group 1 had suppressed TSH and
      26 (62%) had free T4 levels above the upper limit of normal vs none at baseline
      (P < 0.001). The group 2 patients maintained their inhibited TSH values after
      treatment with Dexnon, and the free T4 was above the upper limit of normal in 15
      (94%) vs 3 (19%) at baseline (P < 0.001). The Levothroid tablets collected from
      the patients in both groups formed part of those which the manufacturer later
      withdraw from the market. These batches possessed the correct dosage, but they
      had been made from 'non-micronized' raw materials from another supplier.
      CONCLUSIONS: The most probable cause of the inadequate TSH suppression in our
      patients was the reduction in bioavailability in certain batches of Levothroid,
      although we are unable to rule out the possibility that the results obtained
      after the changeover to Dexnon were due to its greater bioavailability. Simple
      changes in the manufacture of levothyroxine tablets may produce important
      variations in their bioavailability, having an adverse effect on the clinical
      control of the patients, and causing extra expense by the need for repeated
      patient visits and thyroid function tests.

PMID- 9274703
TI  - The thyrotrophic role of human chorionic gonadotrophin (hCG) in the early stages
      of twin (versus single) pregnancies.
AB  - OBJECTIVE: Human chorionic gonadotrophin (hCG) is known to possess thyroid
      stimulating activity. The aim of the present study was to assess the role of hCG
      in stimulating the maternal thyroid gland in the early stages of normal
      gestation. STUDY DESIGN: Thirty euthyroid healthy women were investigated
      prospectively. In each, conception had been assisted by in vitro fertilization
      techniques, which allowed for the precise determination of gestational age. Women
      were subdivided into single (n = 17) and twin (n = 13) pregnancies. Serum intact
      hCG and its free alpha and beta subunits, TSH and free T4 concentrations were
      measured at 6, 8, 9, 10, 11, 15, 19, 22 and 32 weeks. RESULTS: In twin
      pregnancies compared with single pregnancies, peak hCG concentrations (9-11
      weeks) were significantly higher (mean +/- SE 171,000 +/- 12,500 vs 65,500 +/-
      7600 U/l; P < 0.001), and also much more prolonged. Human CG concentrations above
      75,000 U/l lasted for less than 1 week in single, compared with up to 6 weeks in
      twin pregnancies. Free beta-hCG subunit concentrations paralleled those of intact
      hCG in both groups. The ratios of free beta-hCG subunit/total hCG were similar in
      single and twin pregnancies, and did not vary with gestation time. Concerning
      thyroid function, twin pregnancy was more frequently associated with a lowering
      of TSH, which was also more profound than in single pregnancies. Furthermore,
      while free T4 levels remained normal in single pregnancies, they were transiently
      supranormal (up to 52 pmol/l) in four twin pregnancies. CONCLUSION: In twin
      pregnancies the placenta produces larger amounts of hCG for a prolonged period of
      time than in single pregnancies. Both the amplitude and duration of hCG
      production (i.e. the global exposure of the thyroid gland to hCG) are responsible
      for increased thyroidal stimulation, leading more frequently to increased free T4
      and suppressed TSH levels. The results emphasize the role of hCG in stimulating
      maternal thyroid function in the first trimester of pregnancy. Even though the
      production of a variant hCG molecule with potent thyrotrophic activity cannot be
      excluded, this hypothesis is not required to explain the data. Clinicians should
      be aware of the frequent occurrence of significant but transient biochemical
      hyperthyroidism associated with hCG stimulation in the early stages of gestation,
      particularly in twin pregnancies.

PMID- 9274704
TI  - Serum leptin through childhood and adolescence.
AB  - OBJECTIVE: Leptin is the protein product of the recently cloned ob gene, that has
      been implicated in the control of body weight and thermogenesis, but also
      independently stimulates the reproductive axis. As major changes in body
      composition and gonadal function occur during human adolescence, we have assessed
      serum leptin concentration through childhood. SUBJECTS AND MEASUREMENTS: Serum
      leptin was measured in a radioimmunoassay in samples from 235 healthy children
      from 5 to 18 years of age. Its relationship to body mass index (BMI) (expressed
      as standard deviation score (SDS)) and the changes in concentration both within
      and between sexes over the stages of puberty were analysed. RESULTS: Serum leptin
      was present at similar concentrations in both sexes over the prepubertal years
      and increased in parallel into early puberty (breast stage (B) 2, genital stage
      (G) 2). Thereafter serum leptin in the boys declined to a nadir in G5. In
      contrast in girls, leptin remained constant in mid-puberty rising to a peak at
      B5. Factors influencing leptin (BMI SDS, age and testicular volume) were assessed
      therefore in the pre- and peripubertal stages (B1-2, G1-2) compared to the later
      pubertal stages (B3-5, G3-5). In all groups, leptin was positively correlated to
      BMI SDS (r2 = 38-41% in girls, r2 = 31-35% in boys). However in B1-2 and G1-2,
      leptin was also positively related to age, which contributed a further 27% and
      20% respectively to the variability. In B3-5, age only accounted for an
      additional 5% in leptin variability. In contrast in G3-5, leptin was related
      positively to BMI SDS (r2 = 35%) and negatively to testicular volume (r2 = 24%).
      CONCLUSIONS: The influence of BMI on leptin is a significant factor throughout
      the prepubertal and pubertal years of both sexes. The additional negative effect
      of testicular volume in the boys contributes to the sexual dichotomy in leptin
      concentration at the completion of puberty. The similar rise in leptin over the
      prepubertal years into early puberty in both sexes, related not only to BMI SDS
      but also independently to age, would suggest that leptin may have a facilitatory
      role in human pubertal development.

PMID- 9274705
TI  - Insulin action and hepatic glucose cycling in Cushing's syndrome.
AB  - OBJECTIVE: Although it is well established that hypercortisolism causes insulin
      resistance, the mechanisms responsible for impaired insulin action in Cushing's
      syndrome are unclear. This study investigated the contribution of the
      glucose/glucose-6-phosphate substrate cycle (G/G6P). PATIENTS: Eight patients
      with Cushing's syndrome and seven control subjects were studied. All had normal
      fasting plasma glucose. DESIGN: Insulin action was assessed using the euglycaemic
      glucose clamp at insulin infusion rates of 0.4 and 2.0 mU/kg/min combined with a
      simultaneous infusion of [2(3)H]- and [6(3)-H]-glucose. Glucose/ glucose-6
      phosphate cycle activity was calculated as the difference in glucose turnover
      rates determined separately for [2(3)H]- and [6(3)H]-glucose by selective
      enzymatic detritiation. MEASUREMENTS AND RESULTS: Exogenous glucose infusion
      rates required to maintain euglycaemia were significantly lower in Cushing's
      patients compared to controls, during the 0.4 mU/kg/min (7.8 +/- 1.2 vs 15.7 +/-
      0.5 mumol/kg/min, P < 0.001) and the 2.0 mU/ kg/min insulin infusions (26.2 +/-
      2.8 vs 51.5 +/- 3.5 mumol/ kg/min, P < 0.001). Endogenous glucose production was
      similar in both groups in the postabsorptive state (10.2 +/- 0.3 vs 10.8 +/- 0.4
      mumol/kg/min, P = 0.50) and suppressed to a similar degree during
      hyperinsulinaemia. G/G6P cycle activity was markedly increased in the Cushing's
      group in the postabsorptive state (5.4 +/- 1.1 vs 2.0 +/- 0.5 mumol/kg/min, P =
      0.028) and during the 0.4 mU/kg/min (3.2 +/- 0.6 vs 1.2 +/- 0.4 mumol/kg/min, P =
      0.014) and 2.0 mU/kg/min insulin infusions (3.3 +/- 0.8 vs 1.1 +/- 0.5
      mumol/kg/min, P = 0.049). CONCLUSIONS: Patients with Cushing's syndrome show
      marked peripheral insulin resistance and enhanced hepatic G/G6P cycle activity.
      In the fasting state increased glucose/glucose-6-phosphate cycle activity may be
      a protective mechanism limiting hyperglycaemia. During hyperinsulinaemia G/G6P
      cycle activity was increased but insulin resistance was predominantly due to
      reduced peripheral glucose uptake.

PMID- 9274706
TI  - Cabergoline treatment of acromegaly: a preliminary dose finding study.
AB  - OBJECTIVES: Studies of the dopamine agonist cabergoline in the treatment of
      hyperprolactinaemia have shown it to be a potent, long-acting and well-tolerated.
      The older dopamine agonist, bromocriptine, has traditionally had a place in the
      medical management of acromegaly, but poor patient tolerance of the high doses
      required, the need for multiple daily administration and incomplete biochemical
      responses have limited its role. We therefore sought to investigate the effect of
      cabergoline on growth hormone (GH) secretion in acromegaly and to define the most
      appropriate dose for suppression of GH DESIGN AND MEASUREMENTS: Patients with
      active acromegaly (defined as most recent random GH > 5 mU/l) were identified
      from the departmental clinical information system. After informed consent was
      obtained, basal GH levels were estimated during a 5 point day curve at least 2
      months after withdrawal of any existing medical therapy for acromegaly. The
      cabergoline dose was escalated on a monthly basis for 4 months with a repeat 5
      point GH day curve at the highest dose, and 0900 and 0930 GH estimations at the
      intermediate dose increment stages. Serum IGF-1 and prolactin were estimated on
      each occasion. Biochemical remission was defined as serum GH < 5 mU/l. PATIENTS:
      Eleven acromegalics were investigated. Previous treatment included surgery (7),
      radiotherapy (5) and bromocriptine (5). Three patients had not received any
      previous treatment. All had random GH persistently > 5 mU/l prior to the study.
      RESULTS: Ten patients completed the study. Of these, 7 showed a fall in the GH to
      < or = 33% and IGF-1 to < or = 67% of the basal value but only 2 achieved
      biochemical remission. All subjects showed maximum GH response at a dose of 0.5
      mg daily of cabergoline. Four patients were unable to tolerate the maximum dose
      of 1 mg daily (nausea in one and nonspecific symptoms in three). The patient
      excluded from the analysis discontinued cabergoline and underwent surgery after 1
      month because of worsening visual field defects. CONCLUSIONS: Cabergoline may be
      a useful adjunct to the currently available treatment for acromegaly, but rarely
      achieves the goal of mean GH < 5 mU/l. The maximum suppression of GH is achieved
      within the dose range 1 mg twice weekly to 0.5 mg daily.

PMID- 9274707
TI  - Leptin levels do not change acutely with food administration in normal or obese
      subjects, but are negatively correlated with pituitary-adrenal activity.
AB  - BACKGROUND: Leptin is a peptide secreted by white adipose tissue which has been
      shown to have a major influence on body weight regulation, while animal studies
      have revealed widespread interconnections between leptin and other endocrine
      systems, especially with insulin. However, its acute regulation has been little
      studied in the human. We have therefore investigated the effect of a 1000 kcal
      meal and fasting on the levels of leptin, insulin and cortisol, in both normal
      and obese subjects. SUBJECTS AND DESIGN: We have studied the effect of food and
      fasting on circulating leptin levels in 20 subjects of normal body mass index
      (BMI range 18-25) and in a group of 12 moderately-severely obese subjects (BMI
      range 34-61). We also studied the effect of food and fasting in a patient both
      before and after the successful removal of a pancreatic insulinoma as a model of
      excess insulin secretion. RESULTS: Mean leptin levels were significantly higher
      in the obese than in the lean group (42.7 +/- 3.41 vs 5.35 +/- 1.55 micrograms/l,
      mean +/- SEM; P < 0.001), and showed a positive correlation with body mass index
      (r = +0.71; P < 0.001). Frequent (every 20 minutes) sampling for 3 hours after
      food did not show any acute changes in circulating leptin levels. On the fasting
      day we observed a small but significant fall in circulating leptin levels in the
      last 4 hours of a 20-hour fast in our subjects as a group (92 +/- 0.03% of basal,
      P = 0.03); however, in the lean subjects the fall was greater (86 +/- 0.04% of
      basal, P = 0.02) than in the obese, where it did not reach statistical
      significance (96 +/- 0.05% of basal). Pre-meal and peak insulin levels showed a
      positive correlation with circulating mean leptin levels (r = +0.65; P < 0.001
      and r = +0.78; P < 0.001, respectively) in all subjects, while pre-meal and peak
      serum cortisol levels showed an inverse relation with leptin levels (r = -0.53; P
      = 0.002 and r = -0.41; P = 0.02, respectively); this effect was independent of
      BMI in the obese subjects. In the patient with the insulinoma the markedly
      elevated insulin and leptin levels measured before the operation returned to
      normal after removal of the tumour, in accord with reports of experimental animal
      data that long-term insulin excess per se is associated with increased
      circulating leptin concentrations. CONCLUSION: Leptin is a robust indicator of
      BMI and insulin levels, both basal and stimulated, but does not change acutely
      following food. Fasting causes a proportionately greater decline in leptin levels
      in lean subjects than in obese subjects. Circulating leptin is inversely
      correlated with the activity of the hypothalamo-pituitary-adrenal axis: whether
      this is a direct influence of leptin on hypothalamo-pituitary-adrenal activity,
      or whether both are indirect indicators of body fat stores, requires further
      investigation.

PMID- 9274708
TI  - Fluctuating hyper-hypocortisolaemia: a variant of Cushing's syndrome.
AB  - We present a patient with severe Cushing's syndrome secondary to an invasive
      pituitary tumour. Cortisol secretion fluctuated between severe hypercortisolaemia
      associated with features of Cushing's syndrome to recurrent symptomatic
      hypocortisolaemia. Normal ACTH precursors to ACTH ratio during the various stages
      of cortisol secretion indicated that periodic decreased prohormone processing did
      not contribute to the unique presentation in the patient. Thus, the the extreme
      fluctuations of plasma cortisol levels are most probably due to unexplained
      erratic changes of ACTH secretion.

PMID- 9274709
TI  - Corticotrophic macroadenoma of the pituitary associated with hypoadrenalism.
AB  - A 60-year-old man underwent transfrontal surgery for a macroadenoma of the
      pituitary which presented with chiasmal compression, and immunohistochemical
      examination of the resected specimen revealed a corticotrophic tumour. Despite
      subsequent external irradiation, he was left with a large tumour remnant, which
      continued to grow. There were no clinical signs of Cushing's syndrome either
      before or after surgery and 24 h urine excretion of cortisol was not elevated.
      Plasma ACTH concentrations were marginally raised. However, there was loss of
      circadian variation in serum cortisol concentrations and administration of high
      dose oral dexamethasone was followed by a marked and reproducible rise in both
      ACTH and cortisol. Two years later he developed symptoms and signs of
      hypoadrenalism and urine cortisol excretion was low, even though the paradoxical
      response to dexamethasone was preserved. Treatment with 0.5 mg dexamethasone each
      day was associated with partial resolution of his symptoms and urine cortisol
      concentration rose into the normal range. This treatment was maintained until his
      death in hospital in April 1988. The possible mechanism underlying the
      association between a corticotrophic tumour and hypoadrenalism are discussed.

PMID- 9274710
TI  - Thyroid dysfunction in patients with amyloid goitre.
AB  - OBJECTIVES: Widespread amyloid deposition in the thyroid gland causes diffuse,
      clinically apparent enlargement of the thyroid (amyloid goitre: AG). The aim of
      this study was to clarify the abnormalities of thyroid function in patients with
      AG. DESIGN: Thirty patients with secondary amyloidosis were retrospectively
      analysed. Their thyroid status was evaluated using the results of routine thyroid
      function tests and measurement of thyroid autoantibodies. Thyroid needle biopsy
      was carried out to identify amyloid deposition in the thyroid gland. RESULTS:
      Thyroid enlargement was observed in 19 (63%) of 30 patients with amyloidosis.
      Eleven of these 19 patients had a thyroid biopsy and/or autopsy and amyloid
      deposition was histologically revealed in 10 (defined as AG) of these 11
      patients. Nine of 10 patients (90%) with AG had abnormalities of thyroid
      function, including five patients with hypothyroidism, one with hyperthyroidism,
      one with transient hypothyroidism, and two with low T3 syndrome. Five had thyroid
      autoantibodies. The patient with hyperthyroidism had positive thyroid stimulating
      antibody (TSAb) and high 131I thyroidal uptake, suggesting the coexistence of
      Graves' disease. Another patient suffered from thyroidal pain and showed
      transient hypothyroidism, high level of serum thyroglobulin and low thyroidal
      uptake of 123I, the clinical course being compatible with subacute thyroiditis.
      CONCLUSIONS: The incidence of thyroid abnormalities accompanied by AG, although
      asymptomatic, is unexpectedly high. Thyroid function should therefore be
      regularly assessed during follow-up of patients with systemic amyloidosis.

PMID- 9274711
TI  - Short synacthen test versus insulin stress test for the assessment of the
      hypothalamo-pituitary axis: controversy revisited again.

PMID- 9274712
TI  - Pulmonary thromboembolism after inferior petrosal sinus sampling in Cushing's
      syndrome.

PMID- 9274713
TI  - The importance of epidermal stem cells in keratinocyte-mediated gene therapy.

PMID- 9274714
TI  - CFTR gene transduction in neonatal rabbits using an adeno-associated virus (AAV)
      vector.
AB  - Patients with cystic fibrosis develop lung disease after birth, therefore CFTR
      gene replacement therapy should be most efficacious in the neonatal period prior
      to the onset of pulmonary damage. An adeno-associated virus (AAV) vector, SA306
      (Flotte TR et al Proc Natl Acad Sci USA 1993; 90: 10613-10617), which contains
      the AAV inverted terminal repeats flanking the human CFTR cDNA linked to an amino
      terminal epitope tag, was used to transduce a human CFTR fusion protein into
      neonatal New Zealand white rabbits. Vector inocula of 1 x 10(5) to 5 x 10(10)
      particles were given by intratracheal instillation on day 3 of life and the
      rabbit lungs were studied at 3 or 4 days, 2-6 weeks, or 6 months after infection;
      the 2-6 week time-point corresponds to the completion of the alveolar phase of
      lagomorph lung development. Vector DNA was detected by an in situ polymerase
      chain reaction (PCR) using vector-specific primers at up to 6 weeks after
      inoculation. Human CFTR mRNA was detected by Northern analysis at up to 2 weeks
      after vector inoculation, and by a reverse transcriptase PCR assay at up to 3
      weeks after infection. Epithelial expression of the human CFTR fusion protein was
      detected using antisera to both the human CFTR R domain and the amino-terminal
      epitope at up to 6 weeks after vector inoculation. Vector DNA, mRNA, or human
      CFTR immunoreactivity were not observed at the 6 month time-point. Rabbits
      infected with SA306 were clinically indistinguishable from their uninfected
      litter mates. These data indicate that CFTR gene transduction using an AAV vector
      is feasible in the neonatal rabbit, and that expression of vector-derived CFTR
      persists throughout the alveolar phase of lung development. The apparent lack of
      vector persistence after the alveolar phase may reflect dilution of transduced
      cells by further lung growth or a lack of transduction of pulmonary epithelial
      stem cells.

PMID- 9274715
TI  - Persistent transgene expression in mouse liver following in vivo gene transfer
      with a delta E1/delta E4 adenovirus vector.
AB  - Extensive in vivo gene transfer studies in animal models and human gene therapy
      clinical trials with E1-deleted adenovirus vectors have demonstrated transience
      of transgene expression due to direct cytopathic effects of the vectors and host
      immune response to virally expressed proteins. In order to overcome these
      difficulties, we have recently developed packaging cell lines which support the
      growth of adenovirus vectors containing lethal deletions in both E1 and E4 gene
      regions. Here we demonstrate that use of E1/E4-deleted adenovirus vectors leads
      to prolonged in vivo transgene expression due to elimination of cytopathic
      effects and significant reduction of virus-specific immune response.

PMID- 9274716
TI  - Mini-dystrophin gene transfer in mdx4cv diaphragm muscle fibers increases
      sarcolemmal stability.
AB  - To date, all dystrophin gene transfer studies have been performed on mdx hindlimb
      skeletal muscles which in comparison to the severe deficits seen in muscles from
      patients afflicted with Duchenne muscular dystrophy (DMD), exhibit only modest
      morphological and functional changes. Since the mdx diaphragm muscle presents the
      same pathophysiological alterations characteristic of DMD muscles, we therefore
      injected recombinant plasmid DNA encoding the dystrophin mini-gene (pRSVdy-B)
      into diaphragm muscles of 10-week-old mdx4cv mice and examined the physiological
      consequences of dystrophin expression in a muscle that has undergone a phase of
      massive degeneration and regeneration. Immunoperoxidase and immunofluorescence
      experiments revealed that 1 and 3 weeks following gene transfer, approximately
      17% of the fibers in a bundle of diaphragm muscle expressed dystrophin at the
      sarcolemma. Most importantly, this level of dystrophin expression was sufficient
      to protect all fibers present within these diaphragm muscle bundles from the
      damaging effects of repetitive lengthening contractions. In addition, dystrophin
      expression partially restored the ability of transduced mdx4cv muscle bundles to
      generate isometric tetanic tension following lengthening contractions. These
      results show that mini-dystrophin expression leads to rapid and significant
      functional improvements in diaphragm muscles of mdx4cv mice. Although these data
      provide encouraging results for future therapeutic strategies aimed at curing
      DMD, additional work will none the less be necessary to determine the full impact
      of dystrophin gene replacement. In this context, it is clear from the data
      presented here that the diaphragm muscle of the mdx mouse is an invaluable model
      system to address this critical issue.

PMID- 9274717
TI  - Coupling of cell-binding ligands to polyethylenimine for targeted gene delivery.
AB  - Recently the high transfection potential of the cationic polymer polyethylenimine
      (PEI) was described (Boussif O et al. Proc Natl Acad Sci USA 1995; 92: 7297
      7301). To combine the promising DNA delivering activity of PEI with the concept
      of receptor-mediated gene delivery, cell-binding ligands (transferrin or antiCD3
      antibody) were incorporated by covalent linkage to PEI. DNA complexes of PEI or
      ligand-PEI conjugates were tested for transfection of cultured neuroblastoma
      Neuro 2A cells, melanoma B16 or H225 cells, erythroid leukemic K562 cells and T
      cell leukemia Jurkat E6.1 cells. Depending on the cell line, incorporation of the
      cell-binding ligand resulted in an up to 1000-fold increased transfection
      efficiency. This activity depends on ligand-receptor interaction and was observed
      also at low PEI cation:DNA anion ratios where ligand-free PEI lacks efficiency.
      Depending on the cell-binding ligand, specific targeting (CD3 antibody, Jurkat
      cells) can be achieved. Gene transfer can be augmented by the addition of an
      endosome-destabilizing influenza peptide, but is not dependent on the presence of
      additional endosomolytic agents. Application of transferrin-PEI for the
      production of murine interleukin-2 in B16 cells resulted in exceptionally high
      secretion rates of 19 micrograms IL-2 protein per 10(6) cells per 24 h.

PMID- 9274718
TI  - Phase I study of immunotherapy of hepatic metastases of colorectal carcinoma by
      direct gene transfer of an allogeneic histocompatibility antigen, HLA-B7.
AB  - We have completed a phase I study to test feasibility and toxicity of
      immunotherapy of hepatic metastases from colorectal carcinoma by direct gene
      transfer of HLA-B7, a MHC class I gene. Eligible patients were HLA-B7 negative,
      immunocompetent by PHA lymphocyte stimulation and had at least two measurable
      hepatic lesions on CT scan for measurement of response of the injected lesion, as
      well as evaluation of possible distant response. Under ultrasonographic guidance
      the hepatic lesions were injected with Allovectin-7, a liposomal vector
      containing the combination of the HLA-B7 gene with beta 2-microglobulin
      formulated with the lipid DMRIE-DOPE. Eligible patients were injected on two
      schedules. On the first schedule patients received an injection on day 1 and the
      injected lesion was biopsied to determine transfection every 2 weeks for 8 weeks.
      Doses were escalated from 10 micrograms to 50 micrograms to 250 micrograms with
      three patients treated at each level. The second schedule included multiple
      injections of 10 micrograms. Three patients received injections on days 1 and 15.
      Three patients received injections on days 1, 15 and 29. A total of 15 patients
      have completed treatment. The plasmid DNA was detected in 14 of 15 patients (93%)
      by PCR. In five of 15 patients (33%) mRNA was also detected. The HLA-B7 protein
      was detected in five of eight patients (63%) by immunohistochemistry and in seven
      of 14 patients (50%) tested by fluorescence activated cell sorting (FACS)
      analysis. There has been no serious toxicity directly attributable to allovectin
      7. Our results suggest that liposomal gene transfer by direct injection is
      feasible and non-toxic. Further studies will be necessary in order to establish
      the therapeutic efficacy.

PMID- 9274720
TI  - Positive and negative regulation of gene expression in eukaryotic cells with an
      inducible transcriptional regulator.
AB  - To facilitate the understanding of the complex process of target gene expression
      and its control, we report a modified inducible system for activation or
      repression of target gene expression in response to an exogenously administered
      compound. The main component of this inducible system is a chimeric
      transcriptional activator (GLVP) consisting of an N-terminal VP16 transcriptional
      activation domain fused to a yeast GAL4 DNA binding domain and a mutated human
      progesterone receptor (hPR) ligand binding domain (LBD). This chimeric regulator
      binds to a target gene containing the 17-mer GAL4 upstream activation sequence
      (UAS) in the presence of anti-progesterone, RU486. We showed that the combination
      of two different types of domains (VP16 and poly-glutamine stretch) into one
      chimeric molecule could result in a further increase in transcriptional
      activation potency. Through mutational analysis, we modified the original GLVP
      and generated a more potent version of the RU486 inducible regulator GL914 VPc
      with a 19 amino acid deletion of the hPR-LBD (delta C19) and a C-terminally
      located VP16 activation domain. More importantly, this new chimeric regulator can
      effectively activate target gene expression at a much lower concentration of
      RU486 (0.01 nM). The concept of RU486 regulatable gene expression is not limited
      to gene activation. By replacing the VP16 activation domain with a KRAB
      transcriptional repression domain, we are able to achieve inducible repression of
      target gene expression. We also present evidence that individual functional
      domains within a chimeric protein could modulate each other's function depending
      on their relative positions within the molecule. Using this potent regulator, we
      demonstrate that inducible nerve growth factor (NGF) secretion into conditioned
      media can elicit neurite outgrowth in co-cultured PC12 cells. This new versatile
      inducible system can potentially be used to control target gene expression in a
      mammalian system in vivo.

PMID- 9274719
TI  - Kidney-targeted liposome-mediated gene transfer in mice.
AB  - To develop gene therapy targeted to the kidney, we compared three different
      routes of liposome-mediated gene delivery to the kidney in mice, ie intra-renal
      pelvic, intra-renal-arterial, and intra-renal-parenchymal injections. A plasmid
      construct, pCMV beta gal, containing a cytomegalovirus (CMV) immediate-early gene
      promoter and a beta-galactosidase reporter gene was mixed with a 1:1 liposome
      mixture of N[1-(2,3-dioleoyloxy)propyl]-N,N,trimethylammonium chloride
      (DOTMA)/dioleoyl phosphatidyl ethanolamine (DOPE). The pCMV beta gal-liposome
      complex was injected into the left kidney via three different routes. The
      efficacy of gene transfer was assessed using 5-bromo-4-chloro-3-indolyl beta-D
      galactopyranoside (X-gal) staining on frozen kidney sections 3 to 42 days after
      injections. Cells with beta-galactosidase activity were detected in the cortex
      and outer medulla in both intra-renal-pelvic and intra-renal-arterial groups, but
      not in the intra-renal-parenchymal group or in the contralateral noninjected
      kidney. Evidence of gene transfer was observed only in tubular epithelial cells,
      but not in glomerular, vascular, or interstitial compartments. The levels of beta
      galactosidase expression started to decrease 3 weeks after injection. The gene
      transfer in the kidney was not associated with nephrotoxicity as assessed by
      blood urea nitrogen levels and renal histology. We conclude that both intra-renal
      pelvic and intra-renal-arterial injections provide a transient gene transfer to
      the renal tubular cells and are suitable routes for kidney-targeted gene therapy.

PMID- 9274721
TI  - In vitro correction of iduronate-2-sulfatase deficiency by adenovirus-mediated
      gene transfer.
AB  - Hunter syndrome is a lethal lysosomal storage disorder caused by the deficiency
      of iduronate-2-sulfatase and characterized by severe skeletal and neurological
      symptoms. Only symptomatic treatments are available and, although bone marrow
      transplantation has been suggested, no encouraging results have been obtained so
      far. Therefore, gene therapy might be a route to be pursued for treatment of the
      disease. In this respect, one major goal to achieve is the generation of an
      overexpressing vector able to correct, in particular, central nervous system
      (CNS) cells. Adenoviruses have been shown to infect CNS cells efficiently with
      minor or even absent immunological response. We describe the generation of a
      replication-defective adenoviral vector, AdRSVIDS, which is able to express in
      vitro high levels of iduronate-2-sulfatase. After infection, accumulation of
      mucopolysaccharides in treated Hunter cells was normalized. Furthermore,
      endocytosis of the transduced IDS did occur via the mannose-6-phosphate (M6P)
      receptor. Since no animal model for the disease is available, we developed a
      system based on the generation of derma-equivalents which enabled us to verify
      the expression of high levels of sulfatase up to 30 days after infection.

PMID- 9274722
TI  - Delivery of a PCR amplified DNA fragment into cells: a model for using synthetic
      genes for gene therapy.
AB  - Synthetic genes offer many potential advantages over conventional plasmid DNA,
      such as simplicity in purification, absence of endotoxin contamination, and more
      importantly, flexibility in chemical modifications to render them specific
      properties. We have used PCR amplified fragments as a model to test the
      feasibility of using synthetic genes for gene therapy. The CAT reporter gene
      driven by the CMV promoter (CMV-CAT), ie a nuclear expression system, or by the
      bacteriophage T7 promoter (T7-CAT), ie a cytoplasmic expression system, was used
      to evaluate this concept. The expression efficiency of both plasmids (pUCCMV-CAT
      and pT7-CAT) and their corresponding PCR fragments (fCMV-CAT and fT7-CAT) were
      compared on a molar basis. Limited expression of CAT was found with fCMV-CAT.
      However, fT7-CAT consistently gave a CAT activity comparable to that of pT7-CAT.
      When fT7-CAT was codelivered with pCMV/T7-T7pol (a self-amplifying-T7 RNA
      polymerase autogene), high CAT activity could be detected up to 9 days. This
      expression was much longer than the duration of expression with a nuclear
      expression system. These encouraging results imply that gene therapy with
      synthetic genes could be both feasible and efficient.

PMID- 9274723
TI  - Adenovirus-mediated gene transfer into human hepatocytes: analysis of the
      biochemical functionality of transduced cells.
AB  - The use of replication-defective adenoviruses to deliver transgenes into
      hepatocytes seems to be a promising approach to human liver gene therapy.
      However, the effects that the adenovirus-mediated expression of a foreign gene
      could have on the expression of other hepatic characteristic genes have not yet
      been properly examined. We have investigated this problem by using human
      hepatocytes infected with a recombinant E-1 defective adenovirus that carried a
      modified lacZ gene. The analysis of the biochemical functionality of transduced
      cells showed that the use of adenovirus: (1) was a very efficient way to
      introduce a foreign gene into human hepatocytes (80% transduced cells after 1 h
      contact, at an MOI of 15; approximately 100% transduced cells at an MOI of 20);
      (2) allowed the expression of the transgene to levels that enabled cells
      effectively to use lactose as an energy source; (3) does not affect urea
      synthesis, plasma protein synthesis and xenobiotic biotransformation activities
      (1A2, 2A1, 2B6, 3A3/5). Glycolysis was moderately increased (approximately 20%),
      while gluconeogenesis decreased (approximately 20%) in transduced hepatocyte;
      moreover, (4) the expression of inducible genes (acute-phase plasma proteins,
      CYPs) was not impaired in transduced human hepatocytes upon stimulation with IL-6
      or methylcholantrene. The results of this research support the idea that
      efficient expression of transgenes can be achieved in human hepatocytes by means
      of adenoviral transduction, without altering these characteristic hepatic
      biochemical functions.

PMID- 9274724
TI  - Efficient muscle-specific transgene expression after adenovirus-mediated gene
      transfer in mice using a 1.35 kb muscle creatine kinase promoter/enhancer.
AB  - Replication-defective (E1-E3-deleted) human adenovirus vectors are a promising
      means of therapeutic gene delivery to skeletal muscle cells. Since the tropism of
      adenovirus is nonselective, muscle-specific expression of systemically
      administered vectors can only be achieved by the use of a tissue-specific
      promoter/enhancer that is small enough to fit the insert capacity of the vector.
      We have generated two replication-defective adenovirus recombinants (AV) in which
      the reporter gene (either firefly luciferase or E. coli beta-galactosidase) was
      driven by a truncated (1.35 kb) muscle creatine kinase (MCK) promoter/enhancer or
      by the fast troponin I (TnI) promoter/enhancer. Highly efficient and muscle
      specific transgene expression was demonstrated in immunodeficient mice after
      local injection of AV into muscles at an early age. In nonmuscle tissues (brain,
      liver, kidney, lung), the transgene expression was extremely low even though in
      these tissues in situ polymerase chain reaction showed as high an infectivity of
      the cells by the AV as in muscle. The relatively small size, the good efficiency
      and the muscle specificity of the MCK promoter would make it ideal to drive the
      6.3 kb (truncated) dystrophin cDNA in first generation AV (with a limited (8 kb)
      insert capacity) designed for gene therapy of Duchenne muscular dystrophy.

PMID- 9274725
TI  - Adenovirus-mediated gene transfer: influence of transgene, mouse strain and type
      of immune response on persistence of transgene expression.
AB  - E1-deleted adenovirus (Ad) vectors expressing the human coagulation factor IX
      (hFIX) or the bacterial beta-galactosidase (lacZ) were injected intravenously
      into various strains of immunocompetent (C57BI/6, BALB/c, CD1, CBA/J, C3H) and
      immunodeficient (BALB/c-nu/nu, C57BI/6-nu/nu, SCID, NIH-bg-nu-xid) mice. Regular
      analysis of mouse sera and tissues showed a persistent expression of both
      transgenes in immunodeficient mice, while detection diminished very rapidly in
      immunocompetent mice. The mechanisms responsible for the transient detection of
      the two transgenes were however not identical. Rapid decline of lacZ expression
      was correlated with a rapid decrease of viral DNA sequences, and consequently to
      the induction of a cellular immune response to the lacZ antigen. In contrast,
      absence of detectable levels of serum hFIX in immunocompetent animals was not
      associated with a loss of viral DNA but was strictly correlated with the
      induction of anti-hFIX antibodies. Surprisingly, anti-hFIX antibodies were never
      detected in C57BI/6 mice, leading to prolonged detection of hFIX. These results
      suggest that cellular immunity to viral antigens plays a minor role in the early
      extinction of transgene expression and illustrate the influence of the cellular
      (eg lacZ) or humoral (eg hFIX) immunity to transgene-encoded products on the
      persistence of transgene expression.

PMID- 9274726
TI  - Lipofection of a cDNA plasmid containing the dystrophin gene lowers intracellular
      free calcium and calcium leak channel activity in mdx myotubes.
AB  - Muscle cells from Duchenne muscular dystrophy (DMD) patients and the dystrophic
      mdx mouse lack the protein dystrophin. Intracellular free calcium ([Ca2+]i) is
      elevated in Duchenne and mdx myofibers and cultured myotubes and is correlated
      with abnormally active calcium-specific leak channels. Higher [Ca2+]i results in
      greater calcium-dependent proteolysis, which may eventually lead to necrosis. We
      performed liposome-mediated transfection of a cDNA plasmid containing the full
      length dystrophin gene into mdx myoblasts and examined the resting [Ca2+]i and
      leak channel activity of the resulting differentiated myotubes. Many myotubes
      from transfected cultures expressed dystrophin at levels similar to normal
      myotubes as determined by immunostaining. The intracellular free calcium,
      measured by emission ratio microfluorimetry using the calcium indicator fura-PE3,
      was significantly lower in the dystrophin-positive mdx myotubes than in
      untransfected control mdx myotubes. The mean open probability of the calcium leak
      channel was also reduced to a level similar to normal myotubes and significantly
      less than that for untransfected mdx myotubes. These results show that
      introduction of extrachromosomal copies of the full dystrophin gene to originally
      dystrophic muscle cells can correct the defect in calcium homeostasis that is
      hypothesized to lead to the muscle cell necrosis seen in DMD.

PMID- 9274727
TI  - Gene transfer and expression of human alpha-galactosidase from mouse muscle in
      vitro and in vivo.
AB  - Lysosomal storage disorders are amenable to treatment by enzyme replacement.
      Genetic modification of muscle via direct injection of expression vectors might
      represent an alternative method of providing the defective enzymes, if adequate
      and long-lasting expression levels can be achieved in muscle. We have used the
      C2C12 mouse myogenic cell line to study the effect of combination of muscle
      specific regulatory elements on the expression of the human lysosomal enzyme
      alpha-galactosidase (alpha-gal). In differentiated myotubes, a construct
      containing the myosin light chain 1/3 enhancer in combination with the human
      cytomegalovirus promoter resulted in higher expression than constructs combining
      the same enhancer with the rabbit beta-myosin heavy chain promoter, or containing
      the CMV promoter only. Increased enzymatic activity was detectable both in cell
      extracts and in supernatants. Furthermore, human fibroblasts deficient in alpha
      gal were able to take up the enzyme from medium conditioned by transfected
      myoblasts. This did not occur in the presence of mannose-6-phosphate which
      indicates that the uptake was via mannose-6-phosphate receptors. To our
      knowledge, this is the first report in which a correctly processed form of human
      alpha-gal was expressed and secreted from differentiated muscle cells. Direct
      injection of a plasmid expression vector into mouse tibialis anterior muscle
      showed significantly increased levels of alpha-gal 7 days after injection.

PMID- 9274729
TI  - Living colour.

PMID- 9274728
TI  - Adenovirus-mediated expression of green fluorescent protein.
AB  - A recombinant replication-deficient adenovirus has been generated that expresses
      a mutant of the Aquorea victoria green fluorescent protein (GFP) under the
      control of the strong CMV promoter by insertion into the E1 region (AdV-GFP).
      High expression of GFP was found in different cell types after infection with the
      recombinant virus that could be easily detected by fluorescence microscopy. In
      human umbilical vein endothelial cells (HUVEC), expression levels had already
      reached a maximum after 2 days and were stable for at least 7 days, as determined
      by Western blotting. As demonstrated by FACS analysis, up to 98% of HUVEC and
      approximately 70% of human smooth muscle cells could be transduced to express
      GFP. Since GFP can be detected in cells without the need for prior fixing and
      staining, the virus should be useful for optimizing in living cells the
      transduction efficiency of different cell types, of cells from different
      experimental animals, as well as studying the kinetics and persistence of
      adenovirus-mediated gene transfer in diverse experimental settings.

PMID- 9274730
TI  - An audit of trauma documentation.
AB  - Research into aspects of the care of the injured depends on accurate and complete
      documentation. Inadequate records make audit almost impossible and are
      unacceptable medico-legally. An audit was made of the standard of trauma
      documentation in the Yorkshire region before the introduction of trauma charts in
      1992. After it was established that a problem did exist, an audit was made of the
      standard of documentation before and after introduction of trauma charts in one
      city teaching hospital. Case notes were inspected for completeness of
      documentation of respiratory, circulatory and neurological status. Results from
      1988-1989 showed that only 39.4 per cent of notes recorded the four parameters
      under investigation. In 1992-1994 the standard had improved. Without trauma
      charts documentation increased to 90 per cent, but with trauma charts in primary
      referrals the result improved to 97 per cent. Only 56 per cent of notes were
      complete for tertiary referrals when a trauma chart was not used. The standard of
      documentation in major injuries improved with the use of trauma charts. It is
      recommended that trauma charts are used routinely for all primary and tertiary
      referrals of injured patients. Tertiary referral patients should be reassessed
      fully after hospital transfer and a new trauma chart completed.

PMID- 9274732
TI  - Risk factors for 'whiplash' in drivers: a cohort study of rear-end traffic
      crashes.
AB  - 'Whiplash' injuries are a common cause of road traffic accident (RTA) related
      morbidity. However, few epidemiological studies have investigated risk factors
      associated with the occurrence of such injuries. The purpose of this study was to
      examine relationships between vehicle and occupant factors and the incidence of
      'whiplash' in drivers with recent experience of a rear-end impact in an RTA. A
      cohort of 246 car drivers with recent experience of a rear-end impact in the
      Adelaide metropolitan area was recruited. Structured telephone interviews were
      used to obtain information about driver demographics, the circumstances of the
      crash, and injuries resulting from the crash. Two factors were identified as
      independent risk factors for 'whiplash' injury: a history of neck injury
      (adjusted odds ratio = 4.50, 95 per cent confidence interval 1.97-10.28) and
      female sex (adjusted odds ratio = 2.08, 95 per cent confidence interval 1.13
      3.82). The relative weight of the striking vehicle to the driver's vehicle was
      also positively associated with risk of 'whiplash' injury. There was no evidence
      that the driver's occupation or level of education are predictors of occurrence.
      Methodological aspects of the study which might have resulted in bias are
      discussed and suggestions are given for overcoming these in future work.

PMID- 9274731
TI  - Group II phospholipase A2 in serum after knee surgery and intramedullary nailing
      of tibial shaft fracture.
AB  - This prospective study investigates the effect of injury and surgery of cartilage
      and bone on serum group II phospholipase A2 (PLA2-II) and C-reactive protein
      (CRP) levels. Serum concentrations of PLA2-II and CRP were measured before and
      after the operation in nine patients with closed tibial shaft fractures treated
      by nailing, 11 patients with fractures of lateral tibial plateau treated by bone
      grafting, and 19 patients with ruptured anterior cruciate ligament treated by
      reconstruction. The postoperative PLA2-II and CRP values were statistically
      significantly higher than the pre-operative values in the tibial plateau fracture
      and ligament rupture groups, whereas the increase in the PLA2-II values in the
      tibial fracture group was not statistically significant. The highest values of
      both parameters were found on the second postoperative day. The changes in the
      PLA2-II and CRP values were parallel in the lateral condyle fracture and in
      anterior cruciate ligament rupture groups. PLA2-II behaves as an acute phase
      reactant in the serum of patients undergoing acute and elective knee surgery.

PMID- 9274733
TI  - Computed tomography and blunt abdominal injury: patient selection based on
      examination, haematocrit and haematuria.
AB  - The criteria for ordering abdominal CT scans in the secondary survey of stable
      bluntly injured patients was examined. A patient population at high risk for
      having intra-abdominal injury (IAI) was identified by physical examination, a
      fall in haematocrit, and haematuria. A total of 444 patients receiving abdominal
      CT scans at a large urban trauma centre were reviewed. IAI was diagnosed in 49
      (11 per cent), by radiographic and/or intra-operative findings. Abdominal
      tenderness was present in all 17 patients who underwent surgery. The sensitivity
      and specificity of abdominal CT scanning was 90 per cent and 99 per cent,
      respectively. The abdominal exam had a sensitivity of 63 per cent and a
      specificity of 65 per cent. A fall in haematocrit > or = 5 was not statistically
      significant. The combined abdominal exam and haematuria yielded a specificity of
      93 per cent with a negative predictive value (NPV) of 93 per cent. Early CT
      scanning of stable patients who had sustained blunt injuries is an effective
      screen for IAI. The benefit of a CT scan for patients without abdominal
      tenderness or with an isolated fall in haematocrit is questionable. Serial
      abdominal examinations should remain the most timely and cost-effective method
      for identifying IAI in stable patients. The specificity and NPV of abdominal
      tenderness combined with haematuria approaches that of CT.

PMID- 9274734
TI  - Injuries sustained during major evacuation of the high-speed catamaran St Malo
      off Jersey.
AB  - The difficulties and injuries sustained during the emergency evacuation of 308
      passengers and crew from the fast passenger catamaran M.V. St Malo are described.
      The vessel had hit a rock off Jersey and was listing severely. Fifty-three
      passengers were injured, 32 requiring hospital admission; one with a myocardial
      infarction and 31 with musculoskeletal injuries. Eighteen patients required
      operation for severe lower limb injuries. Increased numbers of emergency exits
      and the introduction of evacuation chutes to this type of twin-hulled vessel are
      recommended.

PMID- 9274735
TI  - Cervical spinal injuries caused by collision of cars with camels.
AB  - We report 16 patients who sustained spinal injuries by collision of their cars
      with camels. Out of the 16 patients, 10 had severe spinal injuries with
      neurological deficits. The pattern of injury, possible mechanism of injury and
      recommendations for avoiding these severe injuries are suggested.

PMID- 9274736
TI  - Gunshot injuries of the abdominal aorta: a continuing challenge.
AB  - This is a retrospective study of 57 patients with gunshot injuries of the
      abdominal aorta. The aortic repair was achieved by various means: lateral
      aortorraphy, patch aortoplasty and graft insertion. There was an 85 per cent
      mortality rate from bleeding or secondary coagulopathy directly related to the
      aortic injuries. The need for resuscitative thoracotomy, shock, lack of response
      to fluid resuscitation and intraperitoneal bleeding were directly related to
      mortality. We feel that shortening of prehospital transfer time will increase the
      absolute number of patients surviving this grave injury.

PMID- 9274737
TI  - The development of the growth plate after birth: a study by osteocalcin
      immunocytochemistry.
AB  - The post natal development of the growth plate was studied in the rabbit lower
      limb using an immunocytochemical technique which localized osteocalcin in situ.
      At birth, there is poor columnar organization of the physis and bone is not
      produced. Instead the predominant activity is cartilage remodelling. The columnar
      architecture develops later when endochondral ossification is also observed.

PMID- 9274738
TI  - An analysis of unnatural deaths between 1990 and 1994 in A-Lein, Taiwan.
AB  - This is an analysis of all unnatural deaths (ICD-9, E47-E55) that occurred
      between 1990 and 1994 in A-Lein, Taiwan. Unnatural deaths for this period
      totalled 134, or 89.66 per 100,000 per year. The crude accidental mortality rate
      (E47-E53) and road traffic accident (RTA) mortality rate (E54 is many times
      larger than in other industrialized countries: 2.1-5.1 times and 2.4-7.7 times,
      respectively. These figures are even higher for males. The reported suicide rate
      in A-Lein is approximately equal to that in the UK, but less than other
      industrialized countries. The actual suicide mortality rate in A-Lein as computed
      in this survey was 1.8 times higher than reported, which was 2.4 times that of
      Taiwan as a whole and 2.1 times Great Britain; 30.9 per cent of male and 75 per
      cent of female unnatural deaths excluding RTAs were suicides (ICD-9 E48-E55). RTA
      deaths were 3.2 times higher among males than among females (P < 0.05) and 26.8
      per cent were associated with alcohol consumption. Only 21.4 per cent of killed
      motorcyclists wore helmets and only 8.3 per cent of killed car drivers used seat
      belts. Unnatural deaths excluding RTAs were mostly among people of low socio
      economic status aged 50-60 years with less than a college education. Of these, 75
      per cent occurred at home or at work. The most common cause of non-traffic
      unnatural death excluding RTAs was suicide, and the second most common was
      drowning. In conclusion, it was found that high unnatural death rates in A-Lein
      are related to low socio-economic level, sex (males), drinking, inadequate safety
      protection while working and driving, and inadequate law enforcement.

PMID- 9274739
TI  - A prospective trial to compare three anaesthetic techniques used for the
      reduction of fractures of the distal radius.
AB  - The aim of this study was to compare prospectively haematoma blocks alone and
      haematoma blocks with sedation with general anaesthesia for the reduction of
      distal radius fractures in adult patients, with respect to pain perception
      before, during and after manipulation using a visual analogue scale, radiological
      position, waiting time, procedure time and cost. Fifty-eight adult patients with
      closed, displaced distal radius fractures were included in the study. Pain
      experienced during manipulation was greatest in patients who received haematoma
      blocks alone compared with the other two groups. Post-manipulation pain was
      significantly greater in patients who received a general anaesthetic.
      Radiological correction was as good in those patients receiving a haematoma block
      with or without sedation as a general anaesthetic. The waiting and manipulation
      times and resource costs were greater in those receiving a general anaesthetic.
      There were no complications related to any of these anaesthetic methods. Patient
      acceptance is greater with a correctly performed haematoma block and sedation
      technique compared to general anesthesia. It is also more efficient with regard
      to time and the resources required. This is particularly important for a
      progressively increasing ambulatory, elderly population who require prompt, safe,
      effective and painless management.

PMID- 9274740
TI  - Types of gowns used in trauma and orthopaedic theatres.
AB  - Trauma and orthopaedic surgeons are at an increased risk of acquiring viral blood
      borne infections during elective and especially trauma surgery. The British
      Orthopaedic Association (BOA) published guidelines in 1991 for the prevention of
      cross-infection between patients and staff. It was recommended that only
      waterproof gowns be used in orthopaedic and trauma theatres. The aim of this
      study was to determine the compliance with the BOA recommendations. A telephone
      survey of 79 hospitals in England shows that only a minority (41 per cent) of
      hospitals use waterproof gowns exclusively.

PMID- 9274741
TI  - Possible implication of leukocytes in secondary pathological changes after spinal
      cord injury.
AB  - We reviewed 95 consecutive patients with cervical spinal cord injury admitted
      within 2 days of injury and treated nonoperatively, to elucidate the relationship
      between neurological deterioration and the white blood cell count in the first 4
      days after injury. The count for 14 patients who had neurological deterioration
      was 13.2 +/- 3.2 x 10(9)/l, and that for 81 patients who had no deterioration was
      11.0 +/- 3.1 x 10(9)/l. None of 19 patients whose highest white blood cell count
      was less than 9 x 10(9)l deteriorated, while 14 of 76 patients whose count was 9
      x 10(9)/l or more deteriorated. These results suggest that the white blood cell
      is important in the secondary pathological changes after mechanical injury to the
      spinal cord.

PMID- 9274743
TI  - Distal fracture with hypertrophic non-union: a complication of Seidel humeral
      nail.

PMID- 9274742
TI  - Injuries in military parachuting: a prospective study of 4499 jumps.
AB  - In this prospective study, the parachuting injuries which occurred during 2031
      jumps in basic courses of free fall were compared with the injuries occurring
      during 2468 jumps for reserve paratroopers on training exercises. Fifty-eight
      injuries were recorded in 51 paratroopers. The ankle was most commonly affected,
      and 80 per cent of the injuries involved the lower extremity. Only 14 per cent of
      the injured troopers suffered severe injuries (fractures, knee ligament
      ruptures). The injury rate for paratroopers on basic courses (19.7 injuries per
      1000 jumps) was significantly higher (P < 0.0001) than for those on training
      exercises (4.5 injuries per 1000 jumps). Similar observations were made for
      severe injuries (2.0 versus 1.2 injuries per 1000 jumps, respectively). The
      injury risk increased with age. Most of the injuries occurred on landing, and
      about 70 per cent were mainly caused by improper landing fall technique. The rate
      of serious parachuting injuries was low for Norwegian paratroopers.

PMID- 9274744
TI  - Bilateral wrist fractures from accidental electric shock.

PMID- 9274745
TI  - Pneumomediastinum: an unusual radiographic finding following mid-facial trauma
      injury.

PMID- 9274746
TI  - Intracardiac fluid resuscitation in penetrating cardiac wounds.

PMID- 9274747
TI  - Thromboembolic prophylaxis in orthopaedic trauma patients: a comparison between
      fixed dose and an individually adjusted dose of a low molecular weight heparin.

PMID- 9274748
TI  - Graven images.

PMID- 9274749
TI  - Colour and luminance interact to improve pattern recognition.
AB  - The authors have previously hypothesised that colour vision has evolved not only
      to encode colour per se but also, perhaps principally, to enhance luminance-based
      visual processing so that for colour information to be fully effective, luminance
      as well as chromatic variations should be present in visual targets. Results of
      previous experiments, testing detection of spatial gratings and detection and
      perceived brightness of Mach bands support the hypothesis. Further experiments
      are reported in which the hypothesis was tested by using a higher-level task of
      pattern recognition. Subjects had to discriminate between luminance
      (isochromatic), isoluminant (chromatic), or combined colour/luminance ellipses
      and circles. It was found that the ability to discriminate between a circle and
      an ellipse was greatly enhanced when both colour and luminance variations were
      present as compared with the pure luminance or colour presentations. Summation
      square analysis shows linear colour-luminance summation which can be modeled by a
      single-analyser model.

PMID- 9274750
TI  - The influence of aperture surfaces on the barber-pole illusion.
AB  - The magnitude of the barber-pole illusion is measured as a function of the
      contrast, orientation, and phase difference between the moving 'barber-pole'
      grating and a moving 'surround' grating that forms the aperture surface. It is
      found that as the difference between the barber-pole grating and the surround
      grating increases, the influence of surround motion on barber-pole motion
      decreases (resulting in an increase in the magnitude of the barber-pole
      illusion). This pattern of results is interpreted as evidence for competition
      between processes that detect the motion of line terminators along the length of
      the rectangular aperture and processes that detect grating motion in directions
      perpendicular to grating orientation.

PMID- 9274751
TI  - The perception of surface folding in static and animated displays.
AB  - How do we interpret outline drawings of surfaces? Although pictorial depictions
      are projectively ambiguous, observers demonstrate definite preferences of
      interpretation. Additionally, they commit typical errors. A study is reported of
      one specific arrangement of surfaces as it is represented in outline drawings,
      namely the arrangement that results when two arbitrary surfaces are joined at a
      common edge to form an angle in 3-D ('phenomenic folding'). With some of these
      arrangements, observers report that the angle formed by the two surfaces is zero
      (complete folding). With others, they report that the angles are greater than
      zero (incomplete folding). Both interpretations are actually valid. Several
      investigators have proposed that observer preferences such as these are due t a
      tendency to prefer a 3-D interpretation that will make the depicted 3-D shape
      regular. Three experiments were performed to test this regularisation hypothesis.
      In the first, observers were shown pairs of four-sided polygons joined at one
      equal side. Their task was to imagine how the smaller polygon could be folded
      completely towards the larger, and, subsequently, to report on its position after
      the ('mental folding'). Reported positions were consistent with 3-D
      interpretations that caused figural regularisations, In the second and third
      experiments, observers were shown drawings of diamonds and parallelograms folded
      along a number of differently positioned and oriented segment ('folding edge').
      Their task was to estimate verbally the extent of the dihedral angle formed by
      the two surfaces. Results indicated that the perception of incomplete folding is
      determined by 3-D interpretation of the orientation of the drawing with respect
      of the picture plane. In a fourth experiment, observers were asked whether
      projective equivalences might be disambiguated by animating two kinds of displays
      that yield the 'incomplete folding' effect but that should be distinguishable on
      the basis of the trajectories of the vertexes of the folding parts. Results
      demonstrated that even in these conditions observers are unable to interpret the
      foldings correctly. These results might be taken to indicate that projective,
      static information leading to a simpler and more regular interpretation of the
      display can prevail over explicit motion information that should force the system
      to achieve a nonregular solution.

PMID- 9274752
TI  - Moving cast shadows induce apparent motion in depth.
AB  - Phenomenally strong visual illusions are described in which the motion of an
      object's cast shadow determines the perceived 3-D trajectory of the object.
      Simply adjusting the motion of a shadow is sufficient to induce dramatically
      different apparent trajectories of the object casting the shadow. Psychophysical
      results obtained with the use of 3-D graphics are reported which show that: (i)
      the information provided by the motion of an object's shadow overrides other
      strong sources of information and perceptual biases, such as the assumption of
      constant object size and a general viewpoint; (ii) the natural constraint of
      shadow darkness plays a role in the interpretation of a moving image patch as a
      shadow, but under some conditions even unnatural light shadows can induce
      apparent motion in depth of an object; (iii) when shadow motion is caused by a
      moving light source, the visual system incorrectly interprets the shadow motion
      as consistent with a moving object, rather than a moving light source. The
      results support the hypothesis that the human visual system incorporates a
      stationary light-source constraint in the perceptual processing of spatial layout
      of scenes.

PMID- 9274753
TI  - The effect of attention on phenomenal length.
AB  - The effect of attention of the perceived length of briefly presented peripheral
      lines was investigated. Attention was manipulated by engaging observers in a
      second concurrent task (letter identification). Observers used the method of
      adjustment to indicate the length of the stimulus lines. In two experiments it
      was found that the primary effect of attention was to reduce the variability of
      line length adjustments. Previously investigators had reported that attention
      reduces perceived line length. A third experiment suggested that these previously
      reported results might have been the outcome of a spatial interaction with the
      cue used to manipulate attention, but not the result of visual attention.

PMID- 9274754
TI  - Facial distinctiveness and the power of caricatures.
AB  - Caricatures, which increase the distinctiveness of faces, are generally
      recognised at least as well as undistorted images of those faces. However,
      caricatures seem to facilitate recognition more for some faces than others. An
      investigation was made into whether the effectiveness of caricaturing depends on
      a face's initial distinctiveness. In experiments 1-3, subjects learned names for
      unfamiliar faces (photographs) that varied in distinctiveness, and were tested on
      recognition of caricatures, anticaricatures, and undistorted images of those
      faces. The test images were line drawing in experiment 1 and 2 photographic
      images in experiment 3. Experiments 1 and 2 were identical except that subjects
      had more exposure to the study photographs in experiment 1. In all three
      experiments, distinctive faces were recognised (named) more accurately than less
      distinctive faces, and caricatures were recognised at least as accurately as
      undistorted images and better than anticaricatures. However, distinctiveness and
      caricature level did not interact. Nor did a face's initial distinctiveness
      correlate with the degree of recognition facilitation produced by caricaturing
      (experiments 1-3) or with the caricature level chosen as the best likeness
      (experiment 4). The effectiveness of caricatures varied across faces and
      experimental conditions, but these differences did not relate to differences in
      initial distinctiveness. These results prompted a more careful analysis of the
      expected relationship between initial distinctiveness and the power of
      caricatures, which indicated that the relationship may be curvilinear rather than
      linear. In addition, it was found that line-drawing caricatures functioned as
      superportraits (recognised better than undistorted images--experiment 1) but
      photographic caricatures did not (experiment 3) suggesting that the forensic
      potential of caricatures may be limited.

PMID- 9274755
TI  - The Thatcher illusion as a test of configural disruption.
AB  - Bartlett and Searcy's recent account for the Thatcher illusion suggests that
      inversion impairs holistic facial information. This illusion is used to compare
      the effects of inverting and negating faces. Subjects made a speeded response to
      whether just the mouth and the eyes of a face have been inverted. Performance was
      found to be slower when faces were inverted rather than upright. Presenting faces
      in photographic negative also hindered performance implying that this
      transformation also disrupts holistic facial information.

PMID- 9274756
TI  - Correcting some misperceptions of time-to-collision: a critical note.
AB  - Stewart et al (1993, Perception 22 1227-1224) attempted to demonstrate that the
      ratio of angular speed to angular acceleration, [symbol see text]/[symbol see
      text], of the approaching object is preferred as the source of time-to-collision
      information to the ratio of visual angle to angular speed, [symbol see
      text]/[symbol see text]. It is demonstrated that this is not justified.

PMID- 9274757
TI  - Comparative study of astrocytes in human and rabbit retinae.
AB  - Immunohistochemical location of Glial Fibrillary Acidic Protein (GFAP) was used
      to compare the morphology of astrocytes in vascularized and partially
      vascularized retinae (human and rabbit, respectively). Astrocytes in human and
      rabbit retinae were found in the same regions as the blood vessels. These cells
      in partially vascularized retinae differed from those in vascularized retina in
      several respects. Firstly, there were six morphological types in rabbit retina
      and only two in human retina. Secondly, in rabbit retinae there were astrocytes
      only related to blood vessels called "perivascular astrocytes" which were absent
      in human retinae. Thirdly, the astrocytes were located in the nerve fiber layer
      and ganglion cell layer in both types of retinae, but in human retinae these
      cells could also be seen in the internal nuclear layer. These observations
      demonstrate that there are many differences between astrocytes in human and
      rabbit retina, suggesting that rabbit retina could be used with caution as an
      experimental model in comparative studies with human retina.

PMID- 9274758
TI  - Vernier step acuity and bisection acuity for texture-defined form.
AB  - Using as the stimulus a texture pattern of short lines, we compared positional
      acuity thresholds for an orientation-texture-defined (OTD) boundary and a
      luminance-defined (LD) boundary. Texture lines had different orientations but the
      same luminance on either side of the OTD boundary, and different luminances but
      the same orientation on either side of the LD boundary. For the LD boundary, both
      vernier step acuity threshold and bisection acuity threshold were inversely
      proportional to the number of texture lines per degree (i.e., the pattern's
      spatial sampling frequency) over the entire 1.9-59 samples/deg frequency range
      investigated, though thresholds were considerably lower than the distance between
      adjacent lines. For the OTD boundary, both thresholds were inversely proportional
      to spatial sampling frequency (though thresholds were again considerably less
      than the distance between adjacent lines) but only for sampling frequencies below
      20 samples/deg. For sampling frequencies below 20 samples/deg, the ratio between
      positional acuity thresholds for OTD and LD boundaries was approximately constant
      (3.5:1 for vernier acuity and 1.4:1 for bisection acuity). As sampling frequency
      was increased beyond 20 samples/deg both vernier and bisection acuity thresholds
      for OTD boundaries rose steeply. Both thresholds fell to a minimum near 20
      samples/deg. For vernier step acuity the minimum threshold was 2.3 and 2.4 min
      arc (two observers), and for bisection acuity 1.7 and 1.9 min arc. We propose
      that these minimum thresholds approach a physiological limit of positional acuity
      for an OTD boundary, and that the limit is determined by a balance between the
      progressive improvement of positional acuity caused by increasing the frequency
      of spatial sampling vs the progressive reduction in visibility of the OTD
      boundary caused by the associated reduction in the length of texture lines. These
      physiological limits are far higher than the corresponding limits for sharp-edged
      high-contrast LD targets (2-5 and 1-5 sec arc, respectively). For an OTD boundary
      the effect of orientation contrast on vernier step acuity threshold approximated
      a square root law, while the effect of orientation contrast on bisection acuity
      approximated a linear law. Observers can combine positional information carried
      by texture contrast with positional information carried by luminance contrast. As
      to the combination rule, our findings are consistent with probability summation
      between independent channels.

PMID- 9274759
TI  - Contrast masking effects change with practice.
AB  - Contrast detection thresholds are known to increase with background contrast, a
      phenomenon called contrast masking. We found that, under some conditions,
      observers improved their masked detection performance by repetitive practice of a
      masking experiment. This learning effect resulted in a cancellation of
      suprathreshold contrast masking within the contrast range measured. A two
      alternative forced-choice discrimination paradigm was used, with stimuli
      consisting of Gabor signals as maskers and target, presented at the same location
      and time. Untrained observers showed increased detection thresholds with
      increasing mask contrast for suprathreshold mask contrasts, but perceptual
      learning caused an elimination of this classical effect, with masked thresholds
      reaching the no-mask level and below. Learning did not decrease, but rather
      somewhat increased, discrimination thresholds when target and mask shared the
      same Gabor signal parameters. Performance improvement was found to be specific
      for orientation and mask configurations, though it did transfer between mirror
      symmetric mask configurations and between eyes. These results argue against a
      static transducer function-based account for contrast masking and are consistent
      with a theory assuming multiple feature-based interactive network capable of long
      term gain modifications.

PMID- 9274760
TI  - Capture of the visual direction of monocular objects by adjacent binocular
      objects.
AB  - Investigations of binocular visual direction have concentrated mainly on
      stationary objects. Eye positions were generally not measured and binocular
      fixation was assumed to be perfect. During the viewing of stationary objects,
      vergence errors are not negligible but small. During the viewing of moving
      objects, however, errors in binocular fixation are much larger. Existing rules
      for binocular visual direction were examined under the latter, more demanding
      viewing conditions. Eye movements were measured objectively by the scleral coil
      technique. Subjects viewed a large stereogram in which the half-images oscillated
      in counterphase. The stereogram contained two square random-dot patterns placed
      side by side with a gap in between. A vertical line, visible only to one eye,
      oscillated in the gap. Subjects were asked to adjust the amplitude of line motion
      until the line was perceived to be stationary. In so doing, they set amplitudes
      equal to the amplitudes of half-image motion if the gap between the patterns was
      narrow. They set amplitudes significantly smaller in wider gaps. Subjects made
      considerable fixational errors in following the oscillations of the line and the
      random-dot patterns. The results of the settings and of the retinal errors
      together refute existing rules for binocular visual direction of monocular
      objects. Perceived directions of monocular objects cannot be specified by
      geometrical rules that include only the positions of the objects and of the two
      eyes. The results suggest that perceived directions of monocular objects are
      captured by the binocular visual directions of adjacent binocular objects.
      Capture of binocular visual direction was found to be effective for gaps as wide
      as 8 deg between the binocular objects. The phenomenon of binocular capture has
      negative consequences for the general use of nonius lines as indicators of eye
      position.

PMID- 9274761
TI  - Development of temporal contrast sensitivity in human infants.
AB  - The time course for the development of the temporal contrast sensitivity function
      in humans is uncertain. Some studies indicate that temporal contrast sensitivity
      is immature in infants. However, earlier work suggests that critical flicker
      fusion is adult-like by 2 months. We traced the development of temporal contrast
      sensitivity to uniform field flicker in 2-, 3- and 4-month-old infants using a
      modified preferential-looking technique that employed a rating scale. Two-month
      old infants exhibited highest sensitivities at 1 and 2 Hz. Three- and 4-month
      infants exhibited peak sensitivity at 4 and 8 Hz, respectively. Overall temporal
      contrast sensitivity increased with age and the peak frequency shifted toward
      higher temporal frequencies. Using this paradigm, no infant subjects showed
      responses to 32 Hz, the highest temporal frequencies tested.

PMID- 9274762
TI  - Linking lower and higher stages of motion processing?
AB  - The spatial frequency selectivity of motion detection mechanisms can be measured
      by comparing the magnitude of motion aftereffects (MAEs) as a function of the
      spatial frequency of the adapting and test gratings. For static test gratings,
      narrow spatial frequency tuning has been reported in a number of studies.
      However, for dynamic test patterns, reports have been conflicting. Ashida & Osaka
      [(1994). Perception, 23, 1313-1320] found no tuning whereas Bex et al. [(1996)
      Vision Research, 36, 2721-2727] reported a narrow tuning. The main difference
      between the two studies was the temporal frequency of the test pattern. In this
      study we measured the spatial frequency tuning of the MAE using test patterns for
      a range of temporal frequencies. The results confirmed that there was narrow
      spatial frequency tuning when the test pattern was counterphasing at a low
      temporal frequency. However, the spatial frequency selectivity broadened as the
      temporal frequency of the test pattern was increased.

PMID- 9274763
TI  - The effects of distractor elements on direction discrimination in random Gabor
      kinematograms.
AB  - For both Fourier and non-Fourier moving patterns, models have been proposed which
      detect motion based on either the net orientation of energy in the stimulus
      (after nonlinear stage for non-Fourier motion stimuli) or on the changes in the
      relative locations of spatial primitives in the image. Both approaches have been
      successful in accounting for detection of simple translational displacements, but
      we examined how such models coped with more demanding stimuli. We examined
      direction discrimination using two-flash random Gabor kinematograms which
      selectively reveal Fourier and non-Fourier motion mechanisms. In addition to
      target elements, multiple distractor elements were added, either static or
      randomly moving. It was found that detection of Fourier motion was relatively
      unaffected by the distractors unless they were of orthogonal orientation.
      Detection of non-Fourier motion was possible, but with a slightly higher error
      rate, even with many distractors and was not at all affected by orthogonal
      distractors. The results for distractors of the same orientation as targets are
      in better agreement with predictions of energy than with edge-matching models.
      The differing effects of orthogonal distractors further strengthen the proposed
      dichotomy of quasi-linear and nonlinear motion mechanisms, but indicate that the
      latter operates on a more complex representation than a simple contrast envelope.

PMID- 9274764
TI  - Disparity modulation sensitivity for narrow-band-filtered stereograms.
AB  - Stereo thresholds for 84% correct detection of sinusoidal disparity corrugations
      depicted by narrow-band-filtered random dot stereograms were determined for
      surfaces as a function of (i) luminance center spatial frequency and (ii)
      disparity modulation frequency. In addition, supra-threshold depth matching
      functions for two amplitudes of peak-to-trough depth were determined using
      similar stimuli. Disparity thresholds followed a U-shaped function when plotted
      against luminance centre spatial frequency from 1 to 8 c/deg. The threshold
      functions for the three highest corrugation frequencies (ranging from 0.25 to 1
      c/deg) formed a single family with a similar bandpass shape and a peak
      sensitivity at ca 4 c/deg. At the lowest frequency of depth modulation (0.125
      c/deg) the shape of the luminance spatial frequency threshold function showed a
      reduced sensitivity to depth modulations when portrayed by patterns with high
      luminance centre frequencies (8 c/deg). The similarity of the threshold functions
      reveals luminance and corrugation frequency to be largely independent dimensions.
      The finding that the functions are not identical provides some evidence to
      support a weak luminance spatial frequency selectivity in stereoscopic channels
      tuned to corrugation frequency.

PMID- 9274765
TI  - Saccadic suppression of displacement: separate influences of saccade size and of
      target retinal eccentricity.
AB  - The threshold for detection of displacements of visual objects is higher during
      voluntary saccades than it is during steady gaze ("saccadic suppression of
      displacement"; SSD). Relative contributions to SSD of extraretinal and retinal
      factors were investigated by measuring displacement thresholds in four
      experiments in which three observers judged whether a test flash, presented after
      a saccade or a period of fixation, was located to the left or right of a
      reference point viewed earlier. The experiments, involving saccades ranging from
      4 to 12 deg in length, separated the effects of saccade size from the effects of
      retinal eccentricity of the reference point, and also separated the effects of
      retinal eccentricity of the test flash from both. The influences of the three are
      nearly linearly independent. Approximately 20% of the total influence on SSD
      derives from retinal influences of test flash and reference point; 80% is due to
      extraretinal influence associated with saccade size. A signal/noise model that
      accounted well for our previous on SSD (Li & Matin, 1990a,b) was extended to
      account for the present results. The model also provides a unified treatment of
      SSD and of the saccadic suppression of visibility (SSV).

PMID- 9274766
TI  - Development of smooth pursuit tracking in young infants.
AB  - Eye and head movements were measured in a group of infants at 2, 3, and 5 months
      of age as they were attentively tracking an object moving at 0.2 or 0.4 Hz in
      sinus or triangular mode. Smooth pursuit gain increased with age, especially
      until 3 months. At 2-3 months, the lag of the smooth pursuit was small for the
      sinusoidal motion but large for the triangular one. At 5 months, smooth pursuit
      was leading the sinusoidal motion and the lag for the triangular one was small.
      Head tracking increased substantially with age and its lag was always large.

PMID- 9274767
TI  - Physiological computation of binocular disparity.
AB  - We previously proposed a physiologically realistic model for stereo vision based
      on the quantitative binocular receptive field profiles mapped by Freeman and
      coworkers. Here we present several new results about the model that shed light on
      the physiological processes involved in disparity computation. First, we show
      that our model can be extended to a much more general class of receptive field
      profiles than the commonly used Gabor functions. Second, we demonstrate that
      there is, however, an advantage of using the Gabor filters: similar to our
      perception, the stereo algorithm with the Gabor filters has a small bias towards
      zero disparity. Third, we prove that the complex cells as described by Freeman et
      al. compute disparity by effectively summing up two related cross products
      between the band-pass filtered left and right retinal image patches. This
      operation is related to cross-correlation but it overcomes some major problems
      with the standard correlator. Fourth, we demonstrate that as few as two complex
      cells at each spatial location are sufficient for a reasonable estimation of
      binocular disparity. Fifth, we find that our model can be significantly improved
      by considering the fact that complex cell receptive field are, on average, larger
      than those of simple cells. This fact is incorporated into the model by averaging
      over several quadrature pairs of simple cells with nearby and overlapping
      receptive fields to construct a model complex cell. The disparity tuning curve of
      the resulting complex cell is much more reliable than the constructed from a
      single quadrature pair of simple cells used previously, and the computed
      disparity maps for random dot stereograms with the new algorithm are very similar
      to human perception, with sharp transitions at disparity boundaries. Finally, we
      show that under most circumstances our algorithm works equally well with either
      of the two well-known receptive field models in the literature.

PMID- 9274768
TI  - Implementations of a novel algorithm for colour constancy.
AB  - In agreement with the principles of the relativistic model proposed by
      Creutzfeldt et al., with the photometric rule (lightness anchoring rule) and with
      the influence of simultaneous contrast in the appearance of a visual scene, we
      propose a first-stage mechanism yielding substantial colour constancy. We have
      defined a set of first-stage colour descriptors, and to test their utility, we
      have performed a simulation using a Machine Vision System (MVS). The statistical
      stability of the descriptors for Munsell samples under different illuminants is
      good.

PMID- 9274769
TI  - Contrast dependency of motion-onset and pattern-reversal VEPs: interaction of
      stimulus type, recording site and response component.
AB  - We compared the contrast dependency (from 0.4 to 98%) of the visual evoked
      potential (VEP) to motion onset and to pattern reversal at an occipital and
      lateral recording site using sinewave grating stimuli of 0.9 c/deg, drifting at
      4.9 deg/sec. Two differing VEP components were identified: a positive component,
      peaking at around 130 msec, dominating the occipital derivation, enhanced in
      pattern-reversal stimulation, a high-threshold, late-saturating contrast response
      characteristic with a half-amplitude contrast above 7%; and a negative component
      at around 180 msec, dominating the lateral derivation, enhanced in motion-onset
      stimulation, exhibiting a low-threshold, saturating contrast characteristic with
      a half-amplitude contrast below 4%. The results suggest: (1) The negative
      component (N180) represents motion mechanisms, located more laterally, while the
      positive component (P100-P130) represents form-processing mechanisms, located
      near the V1/V2 areas. (2) A pattern-reversal stimulus triggers both form
      processing and motion mechanisms that can be discriminated by latency. In an
      occipital derivation, the clinical reversal VEP P100 will be little contaminated
      by motion responses.

PMID- 9274770
TI  - Adaptation to the prismatic effects of refractive lenses.
AB  - Adaptation to the simple visual displacement of prisms was compared to that for
      refractive lenses, which have a varied prismatic effect. Subjects were made
      myopic using contact lenses, then corrected using spectacle lenses. The effect on
      the perceived direction of a randomly located target was assessed from pointing
      behavior. Prism adaptation showed a negative directional aftereffect but lacked
      intermanual transfer. Lens adaptation lacked a negative aftereffect but exhibited
      intermanual transfer. The results suggest that lens adaptation involves a
      recalibration of extraretinal eye movement information and multiple sets of lens
      adaptation can be retained for short periods.

PMID- 9274771
TI  - Functional recovery of retina after sodium iodate injection in mice.
AB  - ERGs and the azide responses were recorded from mice before and periodically up
      to 6 weeks after retinal pigment epithelium (RPE) damage by iodate injection to
      follow the recovery of retinal pigment epithelium and retinal function. At 14
      days postinjection, there was a partial recovery of the maximal b-wave amplitude
      and the azide response but no further recovery was found after 14 days. The
      retinal sensitivity showed a slow recovery, and at 6 weeks postinjection did not
      differ from the pre-iodate sensitivity. These findings correlated with
      histological observations. We concluded that the recovery in ERGs resulted from
      RPE recovery and the large patchy area of recovered retina functioned normally.

PMID- 9274772
TI  - Expression of visual and nonvisual opsins in American chameleon.
AB  - We previously characterized five visual opsin genes of American chameleon (Anolis
      carolinensis). Here we report its nonvisual opsin gene orthologous to the chicken
      pineal gland-specific opsin (p-opsin) gene. In the pure-cone American chameleon
      retina, all visual opsins including rod opsin are expressed. In both pineal and
      parietal eye, three visual opsins as well as P-opsin are expressed. Although
      opsins are detected in the pineal glands of a wide variety of vertebrates,
      Southern analysis suggests that the P-opsin gene is used mainly by birds and
      reptiles.

PMID- 9274773
TI  - Independent coding across spatial scales in moving fractal images..
AB  - We compared observers' ability to discriminate the direction of apparent motion
      using images which varied in their spatial characteristic; white or flat spectrum
      noise, and 1/f noise which has an amplitude spectrum characteristic of natural
      scenes. The upper spatial limit for discrimination (dmax) was measured using a
      two-flash random dot kinematogram (RDK), which consisted either of a pair of
      bandpass filtered images or of a bandpass filtered image and its broadband
      counterpart. Six bandpass central frequencies were used, ranging from 0.25 to
      5.66 cyc/deg. Subjects could perform the direction discrimination task for all
      six central frequencies in both the bandpass-bandpass and bandpass-broadband
      sequences for the 1/f images, and dmax values were found to be approximately
      equal in these two conditions at all spatial scales. However, for the white noise
      images, direction discrimination was not possible at the lowest central
      frequencies in the bandpass-broadband task. These data show that information from
      a wide range of spatial scales is equally salient to the human motion system in
      images whose amplitude spectra fall as 1/f. However, for white noise images,
      information at the higher spatial frequencies is more salient and dominates
      performance in the direction discrimination task. These results are consistent
      with a model in which spatial frequency filters in the input lines of motion
      detectors have octave constant spatial frequency bandwidths and equal peak
      sensitivity. In line with a number of recent studies, this suggests that the
      spatial properties of motion sensitive cells are matched to the statistical
      properties of natural scenes.

PMID- 9274774
TI  - Specificity of learning curvature, orientation, and vernier discriminations.
AB  - Training significantly improves the performance of many perceptual tasks.
      Different visual tasks share some "front-end" neuronal mechanisms but rely
      (partly) on different neuronal mechanisms for further analysis. Perceptual
      learning might occur on the early common levels of visual information processing
      or else on the later, more specialized levels. Eighteen observers trained in
      three visual hyperacuity tasks, namely curvature, orientation, and vernier
      discrimination that probably share a common first stage of analysis based on
      detection of oriented line elements. Speed of improvement did not differ
      significantly between these tasks. There was no transfer of improvement from one
      task to another, indicating that the neuronal mechanisms underlying the three
      tasks are at least partly non-identical and that learning does not take place on
      the first common levels of analysis. This result constrains the possible
      localizations, in the human brain, of perceptual learning. The study also
      demonstrates that perceptual learning can be used as a tool to increase our
      knowledge on the sequence of operations during (visual) pattern recognition.

PMID- 9274776
TI  - Foveal cone spacing and cone photopigment density difference: objective
      measurements in the same subjects.
AB  - Foveal cone spacing was measured in vivo using an objective technique: ocular
      speckle interferometry. Cone packing density was computed from cone spacing data.
      Foveal cone photopigment density difference was measured in the same subjects
      using retinal densitometry with a scanning laser ophthalmoscope. Both the cone
      packing density and cone photopigment density difference decreased sharply with
      increasing retinal eccentricity. From the comparison of both sets of
      measurements, the computed amounts of photopigment per cone increased slightly
      with increasing retinal eccentricity. Consistent with previous results, decreases
      in cone outer segment length are over-compensated by an increase in the outer
      segment area, at least in retinal eccentricities up to 1 deg.

PMID- 9274775
TI  - Rayleigh match ranges of red/green color-deficient observers: psychophysical and
      molecular studies.
AB  - Large-field Rayleigh match ranges were measured in 27 red/green color-deficient
      male observers, using bright, temporally alternating, 3-9 deg annular test
      fields. The observers' X-linked opsin gene arrays were characterized by molecular
      genetic techniques, and used to infer the absorption maxima of each observer's L
      and/or M cone photopigment(s). Measured match ranges decreased rapidly as the
      inferred separation in pigment absorption maxima increased from 0 to 2-3 nm, and
      varied irregularly thereafter. Following He & Shevell [(1995) Vision Research,
      35, 2579-2588] predicted match ranges were calculated for various pigment
      separations and assumed values of pigment optical density. The predicted
      variations in match range encompassed the measured match ranges of most (but not
      all) of the color-deficient observers. The calculations also showed that
      differences in pigment optical density, in two cone types containing the same
      pigment, are sufficient to allow a moderate degree of chromatic discrimination.
      Such models thus provide a possible account of the fact that some color-deficient
      observers, with only a single X-linked opsin gene, can make red/green chromatic
      discriminations.

PMID- 9274778
TI  - Context-specific adaptation of vertical vergence to correlates of eye position.
AB  - Vertical phoria (vertical vergence in the absence of binocular feedback) can be
      trained to vary with non-visual cues such as vertical conjugate eye position,
      horizontal conjugate eye position and horizontal vergence. These prior studies
      demonstrated a low-level association or coupling between vertical vergence and
      several oculomotor cues. As a test of the potential independence of multiple eye
      position cues for vertical vergence, context-specific adaptation experiments were
      conducted in three orthogonal adapting planes (midsagittal, frontoparallel, and
      transverse). Four vertical disparities in each of these planes were associated
      with various combinations of two specific components of eye position. Vertical
      disparities in the plane were associated with horizontal vergence and vertical
      conjugate eye position; vertical disparities in the frontoparallel plane were
      associated with horizontal and vertical conjugate eye position; and vertical
      disparities in the transverse plane were associated with horizontal vergence and
      horizontal conjugate eye position. The results demonstrate that vertical vergence
      can be adapted to respond to specific combinations of two different sources of
      eye-position information. The results are modeled with an association matrix
      whose inputs are two classes of eye position and whose weighted output is
      vertical vergence.

PMID- 9274777
TI  - Implicit masking constrained by spatial inhomogeneities.
AB  - Human contrast sensitivities to gratings were measured within windows of 3, 9.1
      and 61.5 deg at spatial differences down to the nominal frequency of 0 c/deg
      (i.e., a uniform field), and the resulting curves were related to the Fourier
      spectra of the corresponding windows and of spatial inhomogeneities in the visual
      pathway. The data show that sensitivity approaches an asymptote about 1.5 log
      units below peak sensitivity as spatial frequency decreases, the so-called low
      frequency cut. Computations show that the fundamentals of the test files used
      here were detected and not their harmonics, and control experiments suggest that
      the edges of the gratings did not affect detection of the gratings. Most of the
      low frequency cut could be attributed to masking by the harmonics of the windows
      within which the gratings were introduced. The added contribution of the
      inhomogeneities in the retinal distribution of cones accounts for the remainder
      of the low frequency cut observed with the two smaller windows, and adding the
      effects of the inhomogeneities to the distribution of parvocellular ganglion
      cells accounts for the remainder of the low frequency attenuation with the
      largest field. Therefore, the attenuation of sensitivity to low frequencies that
      gives the contrast sensitivity curve its bandpass shape can be attributed
      entirely to implicit masking, i.e., to masking by the Fourier spectrum of the
      window within the test grating is presented, after further spreading by retinal
      inhomogeneities.

PMID- 9274779
TI  - Visual-motor optimization in binocular control.
AB  - When we view objects at various depths, the 3-D rotations of our two eyes are
      neurally yoked in accordance with a recently discovered geometric rule, here
      called the binocular extension of Listing's law; or L2. This paper examines the
      visual and motor consequences of this rule. Although L2 is a generalization of
      Listing's original, monocular law, it does not follow from current theories of
      the latter's function, which involve minimizing muscle work or optimizing certain
      aspects of retinal image flow. This study shows that a new optimization strategy
      that combines stereo vision with motor efficiency does explain L2, and describes
      the predictions of this new theory. Contrary to recent suggestions in the
      literature, L2 does not ensure vision of lines orthogonal to the visual plane,
      but rather reduces cyclodisparity of the visual plane itself; and L2 does not
      arise because a single, conjugate angular velocity command is sent to both eyes,
      but actually requires that the two eyes rotate with different speeds and axes
      when scanning an isovergence surface. This study shows that L2 is compatible with
      a 1-D control system for vergence alone (because horizontal and torsional
      vergence are yoked) and a 3-D system for combined, head-fixed saccades and
      vergence.

PMID- 9274780
TI  - Is facilitation responsible for the "motion induction" effect.
AB  - When a horizontal bar is presented after a single dot is shown at one of its
      ends, an illusory motion is seen which has been dubbed "motion induction" in the
      literature. The phenomenon has been attributed to a facilitation process which
      asymmetrically modulates the inputs to motion detectors, for instance by some
      sort of changes in processing speed. Computer simulations of motion detector
      arrays show, however, that this basic effects has to be expected from the
      properties of simple motion detectors. It has been recently reported that the
      strength of the illusory motion increases with the subjective salience of the
      inducing element. New computer simulations demonstrate that this observation can
      be related to the control of the local gain of motion detector input signals by
      the feature contrast in a particular region of the stimulus. High-level
      attentional mechanisms or changes in transmission speed are not required to
      explain these phenomena. The implications of such local gain-control mechanisms
      for our understanding of second-order motion perception are discussed.

PMID- 9274781
TI  - Gender discrimination and prediction on the basis of facial metric information.
AB  - Horizontal and vertical facial measurements are statistically independent.
      Discriminant analysis shows that five of such normalized distances explain over
      95% of the gender differences of "training" samples and predict the gender of 90%
      novel test faces exhibiting various facial expressions. The robustness of the
      method and its results are assessed. It is argued that these distances (termed
      fiducial) are compatible with those found experimentally by psychophysical and
      neurophysiological studies. In consequence, partial explanations for the effects
      observed in these experiments can be found in the intrinsic statistical nature of
      the facial stimuli used.

PMID- 9274782
TI  - Responses to chromatic and luminance contrast in glaucoma: a psychophysical and
      electrophysiological study.
AB  - Increasing anatomical evidence indicates that large retinal ganglion cells (M
      cells) are preferentially damaged in primary open angle glaucoma (OAG), while the
      smaller ganglion cells (P-cells) are relatively spared. In 13 patients with
      defined OAG and modest visual field defects, we evaluated the responses to
      stimuli that are expected to involve primarily the function of the P-pathway and
      compared them with those of control subjects. The psychophysical contrast
      sensitivity (CS), the PERG and the VEPs were measured for red-green gratings of
      pure chromatic contrast, as well as yellow-black gratings of pure luminance
      contrast. As compared with controls, OAG patients had reduced CS for both
      luminance and chromatic contrast stimuli by about 6 dB. PERGs and VEPs to
      luminance stimuli were little affected, whereas those to chromatic stimuli were
      both reduced in amplitude and delayed. These results indicate that visual
      dysfunction in glaucoma is not selective for the M-pathway, and that responses to
      equiluminant colour-contrast stimuli may be of diagnostic value.

PMID- 9274783
TI  - Perimetric motion thresholds are elevated in glaucoma suspects and glaucoma
      patients.
AB  - The purpose of this study was to determine if a clinically feasible perimetric
      motion test utilizing random-dot kinematograms could identify glaucomatous visual
      field defects. Using a staircase procedure, an automated perimetric motion test
      and a larger foveally presented target were given to normal (n = 30), glaucoma
      suspects (n = 31) and primary open-angle glaucoma patients (n = 19). Motion
      thresholds at specific locations throughout the whole visual field were
      significantly elevated in glaucoma patients (P < or = 0.001). Perimetric motion
      testing identified 84.2% of the primary open-angle glaucoma patients and 25.8% of
      the glaucoma suspects as abnormal. A larger foveal stimulus was unable to
      distinguish between the different subject groups (P < or = 0.185). Perimetric
      motion thresholds were significantly correlated with Humphrey standard visual
      field thresholds in the glaucoma and glaucoma-suspect patients (P < or = 0.0002).

PMID- 9274785
TI  - Quality of life.

PMID- 9274784
TI  - Psychophysics of reading--XVI. The visual span in normal and low vision.
AB  - The visual span in reading is the number of characters that can be recognized at
      a glance. The shrinking visual span hypothesis attributes reading deficits in low
      vision, and slow reading in normal vision at low contrast, to a reduction in the
      visual span. This hypothesis predicts that reading time (msec/word) becomes
      increasingly dependent on word length as text contrast decreases. We tested and
      confirmed this prediction using the rapid serial visual presentation (RSVP)
      method. Estimates of the visual span ranged from about 10 characters for high
      contrast text to less than two characters for low-contrast text. Eye-movement
      recordings showed that longer reading times at low contrast are partitioned about
      equally between prolonged fixation times and an increased number of saccades
      (presumably related to a reduced visual span). RSVP measurements for six out of
      seven low-vision subjects revealed a strong dependence of reading time on word
      length, as expected from reduced visual spans.

PMID- 9274786
TI  - Microvessel count predicts metastasis and prognosis in patients with gastric
      cancer.
AB  - BACKGROUND AND OBJECTIVES: In order to evaluate the clinical relevance of
      angiogenesis in patients with gastric cancer, we investigated the microvessel
      count in gastric cancer tissues and compared the results with several
      clinicopathologic factors and prognosis. METHODS: A total of 55 patients with
      gastric cancer were included in this study. Microvessel count was determined by
      immunohistochemical staining using antifactor VIII-related antigen antibody.
      Histologically recognizable blood vessels within tissue sections served as
      internal control for immunostaining. Normal mouse IgG diluted to an equivalent
      protein concentration was used as a negative control in place of the primary
      antibody in each experiment. RESULT: The microvessel count ranged from 4.4 to
      39.8 and the median count was 15.6. Microvessel count was significantly higher in
      patients with hepatic metastasis, lymph node metastasis, adjacent organ invasion,
      and lymphatic invasion. In patients who had undergone a curative operation,
      survival time in the hypervascular group was significantly shorter than that in
      the hypovascular group. CONCLUSIONS: Microvessel count correlated well with tumor
      progression and may serve as a useful prognostic factor in patients with gastric
      cancer.

PMID- 9274787
TI  - DNA flow cytometry in gastric carcinoma: implication in patients with potentially
      curative resection.
AB  - BACKGROUND AND OBJECTIVES: The relevance of DNA ploidy as a prognostic factor in
      patients with gastric cancer is controversial. The prognostic significance of DNA
      ploidy and its relationship to conventional histological grading and staging of
      the tumor (TNM stage, Lauren, Ming and WHO classification) were evaluated.
      METHODS: DNA ploidy of the tumor was determined by flow cytometry on archival
      material from 76 patients who underwent R0, D2 stomach resection. RESULTS: DNA
      aneuploidy was found in 39 cases (51%). No significant association between DNA
      aneuploidy and either patients' sex, pT, pN, type according to Ming or Borrmann
      and tumor localization was found. The incidence of DNA aneuploidy was
      significantly lower in tumors of diffuse type according to Lauren, in signet-ring
      cell or undifferentiated type (WHO), in grade 3/4 tumors, and in patients younger
      than 50 years. We found no significant difference in survival of patients with
      DNA aneuploid when compared to DNA diploid tumors, although the prognosis of the
      patients with lower DNA index (DI < 1.2) tended to be better than that of higher
      DNA index (DI > 1.2). CONCLUSIONS: DNA ploidy appears to be of limited prognostic
      value after R0, D2 resection of stomach cancer.

PMID- 9274788
TI  - Evaluation of cathepsin D immunostaining in colorectal adenocarcinoma.
AB  - BACKGROUND AND OBJECTIVES: Cathepsin D (CD), an estrogen-regulated lysosomal
      protease, has been detected in a variety of tissues. CD expression has been
      correlated with the invasive potential of breast cancer, acting as an autocrine
      mitogen or as a protease that degrades the extracellular matrix. The role of CD
      expression in predicting prognosis or invasive potential in colorectal carcinomas
      is mostly unknown. METHODS: CD immunohistochemical expression was studied in 60
      surgical specimens of colon adenocarcinomas. A three-step avidin biotinylated,
      horseradish immuno-peroxidase (ABC-HRP) staining technique was performed on 4
      microm paraffin-embedded tissue sections with a polyclonal antibody to CD.
      RESULTS: Carcinoma cells showed positive CD immunostaining in 41.6% of
      adenocarcinomas (50%, 43.7%, 37.5%, and 25% of Dukes' Stage A, B, C, and D,
      respectively). Nonneoplastic stromal cells demonstrated positive staining in
      68.3% of the adenocarcinoma specimens (37.5%, 62.5%, 91.6%, and 75% of Stage A,
      B, C, and D, respectively). Patients with colorectal carcinomas exhibiting
      simultaneously negative and positive CD expression in malignant and stromal
      cells, respectively, had a worse 5-year overall survival (P < 0.05). The mean 5
      year survival of the 16 patients overexpressing CD in nonneoplastic stromal cells
      (>15% of stromal cells positive for CD) was significantly worse in comparison
      with the rest of the adenocarcinomas (n = 44) (27.6 +/- 4.6 vs. 46 +/- 2.7
      months, respectively, P < 0.01). CONCLUSIONS: Expression of CD immunoreactivity
      by the stromal cells may be associated with a more invasive phenotype. Therefore,
      CD expression in tumor and stromal cells may serve as an important indicator of
      progression and guide postoperative treatment.

PMID- 9274789
TI  - Cloning, sequence, and developmental expression analysis of C4-2, a potential
      brain tumor-suppressor gene.
AB  - BACKGROUND: Previously, we reported the isolation of C4-2 as a potential tumor
      suppressor gene in human brain tumors. To understand the function of this gene,
      we investigated its molecular characterization and expression during development.
      METHODS: Human fetal brain library screening and 5'RACE-PCR method was used to
      isolate the full-length cDNA. The coding region of C4-2 was used for in situ
      hybridization to study its expression during development. RESULTS: We report here
      the complete sequence of this gene. Sequence analysis indicated that C4-2 has a
      94% sequence identity to a family of cAMP-regulated phosphoproteins (ARPP-16/19)
      in the coding region. C4-2 has a 3.1 Kb long 3'UTR with variable identity to ARPP
      16 and ARPP-19. Northern blot analysis indicated that C4-2 is expressed at high
      levels in normal brain compared to other tissues. Zoo blot analysis demonstrated
      that the coding region of C4-2 is highly conserved among different animals. In
      situ hybridization using C4-2 coding region demonstrated that it follows a unique
      expression pattern during mouse brain development. High level of C4-2 expression
      was also observed in the spinal cord and somites of the developing embryo.
      CONCLUSION: Expression analysis during brain development strongly suggests that
      this family of proteins may play an important role not only in normal functioning
      of the brain, but also during brain development.

PMID- 9274790
TI  - Synchronous primary tumors of the extrahepatic bile duct and gallbladder.
AB  - BACKGROUND AND OBJECTIVES: This study aims to clarify clinicopathologic
      characteristics of synchronous primaries of the extrahepatic bile duct and
      gallbladder. Understanding multiplicity and its histologic confirmation is an
      important step for successful surgical management. METHODS: Of the 190 cases of
      resection of biliary tract neoplasms in this study, 10 had two separate tumors in
      the extrahepatic bile duct and gallbladder, which were investigated by the
      microscopic mapping technique for tumor extent using serial stepwise sectioning
      of specimens. RESULTS: Clinical diagnosis was made successfully in only two
      cases. Detailed histologic examination revealed seven cases with synchronous
      primaries and three cases with metastatic tumors. Several microscopic parameters
      had additional diagnostic value. The presence of synchronous primaries is not
      necessarily associated with a poor prognosis, since we had four long-term
      survivors. CONCLUSIONS: Diagnosis of synchronous extrahepatic biliary neoplasms
      is rarely made preoperatively. However, aggressive resection and careful
      microscopic examination are essential for the successful management and diagnosis
      of these special cases.

PMID- 9274791
TI  - Local resection and brachytherapy confined to the lumpectomy site for early
      breast cancer: a pilot study.
AB  - BACKGROUND AND OBJECTIVES: The commonest site of local breast recurrence after
      breast conservation surgery is the primary tumor bed. We have tested the
      feasibility of outpatient high dose rate brachytherapy to the primary tumor bed
      as the only radiation. Our technique relies on the placement of surgical clips to
      mark the tumor bed. METHODS: Between March 1992 and January 1996, 39 patients
      with clinical T1 T2 breast cancer were enrolled in this pilot study. The first 13
      patients had intraoperative implantation of the breast. The remaining 26 patients
      had outpatient postoperative implantation under general anesthesia (2 patients)
      or local anaesthesia (24 patients). High dose rate brachytherapy was given twice
      daily at least 6 hours apart for a total dose of 37.2 Gy in 10 fractions over 5-7
      days. RESULTS: Three patients had mild clinical cellulitis responding to oral
      antibiotics. One patient had a small sinus in the lumpectomy scar requiring local
      excision to heal. Four patients developed fat necrosis at the lumpectomy site at
      4 (1 patient), 13 (1 patient), and 18 months (2 patients) post radiotherapy.
      Patient rated satisfaction with treatment was high. At a median followup of 20
      months, one infield local recurrence has been salvaged by wider resection and
      postoperative conventional external beam radiation. CONCLUSIONS: Except for fat
      necrosis, which may be associated with this technique, complications have been
      minimal. Outpatient implantation under local anesthesia is feasible. Longer
      followup is required to establish the local control rates.

PMID- 9274792
TI  - Laryngeal chondrosarcomas: the Mayo Clinic experience.
AB  - BACKGROUND: Laryngeal chondrosarcomas occur infrequently. Their management is
      often guided by inferences made from the management of sarcomas arising from more
      commonly afflicted organs. METHOD: A retrospective analysis of patients with
      laryngeal chondrosarcomas treated at the Mayo Clinic between 1959 and 1992 was
      performed to assess prognostic factors and outcomes after various treatments.
      RESULTS: A total of 20 patients received treatment during this time period. All
      chondrosarcomas were low grade; 19 involved the cricoid cartilage and one arose
      in the supraglottic larynx. Initial treatment consisted of local excision (often
      subtotal removal) alone in 12 patients (60%), hemilaryngectomy in 2 (10%), near
      total laryngectomy in 2 (10%), and total laryngectomy in 4 (20%). Six patients
      (30%) had local recurrence: five initially had local excision and one had
      hemilaryngectomy. All local recurrences or tumor progression developed >3 years
      after initial treatment. Salvage surgery was performed in five of the six
      patients who had local recurrence, and the other patient was observed. Of the
      five patients who had salvage surgery, three required another resection because
      of a second recurrence. CONCLUSIONS: These results suggest that initial
      conservative subtotal laryngectomy should be explored further because this
      treatment may provide long-term voice preservation in most patients, and patients
      who experience a recurrence after local excision often have been given several
      years of voice preservation.

PMID- 9274793
TI  - Proliferative activity of esophageal carcinomas and their lymph node metastases:
      comparison using argyrophilic nucleolar organizer region staining.
AB  - BACKGROUND: Many reports have concluded that quantification of the argyrophilic
      nucleolar organizer regions (AgNORs) measures proliferative activity and is a
      prognostic indicator in malignant disease. This retrospective study set out to
      evaluate the relationship between the AgNORs of the primary tumors and those of
      lymph node metastases in esophageal carcinoma. METHODS: Using a one-step silver
      staining technique, AgNORs were counted in surgical specimens from 54 patients
      with squamous cell carcinomas. RESULTS: The AgNOR scores of the lymph nodes
      metastases were significantly lower than those of the primary tumor (P = 0.0001).
      In 53 of 54 cases (98%), the AgNOR scores in the nodal metastases were lower than
      those of the primary tumor. The survival of 22 patients with AgNOR scores > or
      =4.0 for the primary tumor was significantly less than that of 32 patients with
      AgNOR scores <4.0 for the primary tumor (P = 0.0014). CONCLUSIONS: The AgNOR
      score of the lymph node metastases had no prognostic significance. The AgNOR
      score of esophageal primary cancer reflects the prognosis of patients. Scores for
      lymph node metastases were lower and did not reflect prognosis. The lower score
      in the lymph node metastases may result from the antitumor activity of
      macrophages in the lymph nodes.

PMID- 9274794
TI  - Adenocarcinoma in a duplicated bladder.
AB  - We report a rare case of duplication of the bladder, urethra, uterus, vagina, and
      associated anomalies in a woman. As an infant, she initially underwent successful
      surgical reconstruction. As an adult, she developed adenocarcinoma within the
      defunctionalized bladder moiety. The surgical management and pathology of this
      cancer are detailed and the pertinent literature reviewed.

PMID- 9274795
TI  - On the growth rates of human malignant tumors: implications for medical decision
      making.
AB  - Testicular carcinomas, pediatric tumors, and some mesenchymal tumors are examples
      of rapidly proliferating cell populations, for which the tumor volume doubling
      time (TVDT) can be counted in days. Cancers from the breast, prostate, and colon
      are frequently slow-growing, displaying a TVDT of months or years. Irrespective
      of their growth rates, most human tumors have been found: to start from one
      single cell, to have a long subclinical period, to grow at constant rates for
      long periods of time, to start to metastasize often even before the primary is
      detected, and to have metastases that often grow at approximately the same rate
      as the primary tumor. The recognition of basic facts in tumor cell kinetics is
      essential in the evaluation of important present-day strategies in oncology.
      Among the facts emphasized in this review are: (1) Screening programs. Most
      tumors are several years old when detectable by present-day diagnostic methods.
      This makes the term "early detection" questionable. (2) Legal trials. The
      importance of so-called doctor's delay is often discussed, but the prognostic
      value of "early" detection is overestimated. (3) Analyses of clinical trials.
      Such analysis may be differentiated depending on the growth rates of the type of
      tumor studied. Furthermore, uncritical analysis of survival data may be
      misleading if the TVDT is not taken into consideration. (4) Analyses of
      epidemiological data. If causes of malignant tumors in humans are searched for,
      the time of exposure must be extended far back in the subject's history. (5) Risk
      estimations by insurance companies. For the majority of human cancers, the 5-year
      survival rate is not a valid measurement for cure. Thus, basic knowledge of tumor
      kinetics may have important implications for political health programs, legal
      trials, medical science, and insurance policies.

PMID- 9274796
TI  - Biliary tree malignancies: the University of Minnesota experience.
AB  - Because of its slow-growing natural history, most patients with extrahepatic
      biliary tree malignancies present with inoperable disease. For the minority of
      patients with operable disease, surgical resection remains the treatment of
      choice and offers the patient the best chance for long-term local control. The
      role of chemotherapy and radiotherapy in the management of these patients in the
      definitive, adjuvant, and palliative setting is expanding, although unsettled.
      Response rates with chemotherapy have been low and will most likely find a place
      in a combined multimodality setting. Radiotherapy (external beam, intraoperative,
      and intraluminal brachytherapy using 192Ir) has played a major role in the
      treatment of these cancers. The close proximity of bowel, kidney, and liver
      limits the external beam radiotherapy doses that can be safely delivered. Since
      most patients require placement of percutaneous transhepatic biliary catheters to
      relieve jaundice, this route has been utilized to deliver higher doses of
      radiation to the tumor area with intraluminal 192Ir ribbons. The University of
      Minnesota has treated 15 patients with extrahepatic bile duct cancers. Most were
      located at the bifurcation of the common bile duct and were treated with
      intraluminal brachytherapy alone or with external beam radiotherapy. Our results
      are comparable to previously reported retrospective data with a median survival
      of 8 months and three long-term survivors.

PMID- 9274797
TI  - Simulation of lindane kinetics in rats.
AB  - The kinetics of lindane were modelled in the male rat with a physiologically
      based pharmacokinetic (PB-PK) model. The model was parameterized by using
      reference physiological parameter values and partition coefficients that were
      reported earlier in the literature. First order biotransformation and gastro
      intestinal absorption constants for lindane were obtained by visually fitting the
      model to literature data on lindane disposition in vivo after a single oral dose.
      The model was validated by simulating the disposition of lindane in vivo after
      single intraperitoneal and chronic oral dosage and comparing simulated with
      experimental results. It was concluded that the present model can adequately
      simulate most of the reported data on lindane kinetics.

PMID- 9274798
TI  - Evidence for mitochondrial metabolism of 7,12-dimethylbenz(a)anthracene in
      porcine ovaries: comparison with microsomal metabolism.
AB  - 7,12-dimethylbenz(a)anthracene (DMBA) causes necrosis in endocrine organs. DMBA
      metabolism in follicles and corpora lutea from porcine ovaries was demonstrated
      not only in the microsomal but also in the mitochondrial fraction, in contrast to
      what has been found in the rat ovary. Maximal activities were present in these
      fractions of the corpus luteum, with specific activities of 5.9 and 2.2 pmol/min
      x mg protein, respectively. DMBA metabolism in mitoplasts, i.e. mitochondrial
      inner membranes, proved to be more than 10-fold higher than the corresponding
      activity in the mitochondrial fraction. The purities of the subcellular fractions
      were assessed by measurements of marker enzymes. 17-42% of the mitochondrial DMBA
      metabolism was concluded to be due to microsomal contamination. In the mitoplast
      fraction such contamination was only 0.18-2.8%. Ellipticine and alpha
      naphthoflavone reduced the metabolism of DMBA in the luteal microsomal fraction
      by 95 and 77%, respectively. In mitochondria the inhibition by these agents was
      63 and 30%, respectively. Indomethacine and estradiol decreased microsomal DMBA
      metabolism by 53 and 52%, respectively. In mitochondria the inhibition was 52 and
      23%, respectively. None of these inhibitors affected the DMBA metabolism by the
      mitoplast fraction.

PMID- 9274799
TI  - Effects exerted by otilonium bromide administration on precipitated opioid
      withdrawal syndrome in rats.
AB  - An opioid withdrawal syndrome was induced in rats by repeated morphine
      administration and final naloxone injection. The withdrawal causes alteration of
      several physiological signs. The aim of the study was to prevent the altered
      physiological profiles by utilising otilonium bromide. Morphine was administered
      in three daily i.p. injections for 4 days at doses of 9, 16 and 25 mg/kg (1st
      day), 25, 25 and 50 mg/kg (2nd day), 50, 50 and 50 mg/kg (3rd day) and 50, 50 and
      100 mg/kg (4th day). Naloxone was injected (30 mg/kg) i.p. 180 min after the last
      morphine injection. Otilonium bromide was administered orally at 0, 2, 4 and 8
      mg/kg, 120 min before the naloxone administration. Signs like faecal and urine
      excretion, rectal temperature and pain threshold levels, salivation, jumping and
      wet dog shakes were affected in different ways. Notably the administration of
      otilonium bromide in rats receiving morphine together with naloxone decreased the
      intensity of certain withdrawal symptoms, such as excretion of faeces, wet dog
      shake behaviour, and elevated the nociceptive threshold values. The effects
      exhibited by otilonium bromide administration may be explained through its
      calcium antagonist activity interfering with a mechanism involved in the
      regulation of these previously mentioned withdrawal symptoms. The use of this
      drug is thus suggested as a possible control of some acute opioid withdrawal
      signs in heroin addicts.

PMID- 9274800
TI  - Chloroform-induced olfactory mucosal degeneration and osseous ethmoid hyperplasia
      are not associated with olfactory deficits in Fischer 344 rats.
AB  - Adult female F-344 rats were trained (avoidance rate > 70%) over four days with a
      coupled tone- (n = 10 rats/dose) or 2 ppm acetaldehyde-cued (n = 6 rats/dose)
      foot shock paradigm. Rats were gavaged with chloroform dissolved in corn oil for
      5 days/week for 3 week at 0 or 400 (tone-cued) or 0, 34, 100, or 400 (odor-cued)
      mg/kg body weight/day. Tone-cued response was reevaluated 6, 16, and 38 days
      after the first chloroform dose (day 1). Olfaction was assessed on days 6-7, 20
      21, and 41-42 using 2 or 0.0002 ppm acetaldehyde. Nasal histopathology (n = 4-5
      rats/dose) was assessed on days 6, 20, and 42. Significantly decreased body
      weights were observed following a single 100 or 400 mg/kg chloroform dose. Body
      weights in the 400 mg/kg/day chloroform group remained depressed for 17 days.
      Histopathology revealed degenerative changes in olfactory mucosa and underlying
      ethmoid turbinate bones that were essentially identical in nature and severity,
      including dose-response and progression, to those reported previously for
      chloroform gavage (Larson et al., Food Chem. Toxicol., 1995;33:443 456). At all
      dose level and sacrifice timepoints, however, regions of morphologically normal
      olfactory mucosa were present, especially in dorsal medial and ventral lateral
      regions of the nose. Neither odor- nor tone-cued avoidance behaviors were
      affected, indicating that even fairly severe and extensive chloroform-induced
      olfactory mucosal degeneration is not associated with a detectable olfactory
      deficit in rats.

PMID- 9274801
TI  - Kinetics of selenium incorporation into tissues of female mallard ducks.
AB  - Selenium is essential for both mammalian and avian species, although its
      metabolism in birds has been less thoroughly studied. Little information has been
      available on the kinetics of selenium in birds, especially as it relates to the
      teratogenicity seen in waterfowl consuming excessive amounts. This study
      describes the pharmacokinetics of small amounts of 75Se as selenious acid
      injected into female mallard ducks. Labeled selenium was injected into a wing
      vein of restrained animals and tissues taken at five different time points up to
      24 h post-injection. Selenium levels as percent of injected dose were determined
      in liver, kidney, heart, lung, adrenals, thyroid, spleen, pancreas, ovaries,
      intestine, muscle and plasma. Estimates of kinetic parameters (uptake and
      elimination rates, time of maximum concentration and maximum concentration) were
      obtained with a non-linear kinetics computer program (PCNONLIN, SCI Software,
      Lexington, KY). Results showed four basic patterns of distribution, uptake and
      elimination. Visceral tissues exhibited a triphasic pattern with a rapid rise, a
      decline followed by a distinctive increase in levels between the last two time
      points. Brain uptake was continuous over the 24 h. Plasma rose rapidly and then
      declined to a constant level. The ovaries as a tissue of interest relating to the
      teratogenic effects of selenium showed the greatest relative increase at 24 h,
      suggesting kinetic mechanisms consistent with a pathway that might lead to
      accumulation of toxic levels and teratogenic effects during embryo development.

PMID- 9274802
TI  - Effects of co-administration of butylated hydroxytoluene, butylated
      hydroxyanisole and flavonoids on the activation of mutagens and drug-metabolizing
      enzymes in mice.
AB  - Effects of co-administration of food additives and naturally occurring food
      components were studied on the activation of mutagens. Male mice (ddY) were given
      diets containing butylated hydroxytoluene (BHT) or butylated hydroxyanisole (BHA)
      and flavone or flavanone (2,3-dihydroflavone) for two weeks and the ability of
      hepatic microsomes to activate aflatoxin B1, benzo[a]pyrene and N
      nitrosodimethylamine was determined by the mutagenicity test. Co-administration
      of an antioxidant (0.1% BHT or 0.2% BHA in diet) and a flavonoid (0.1% flavone or
      0.1% flavanone) resulted in additive effects on the activation of aflatoxin B1
      and benzo[a]pyrene, while the activation of N-nitrosodimethylamine was not
      elevated significantly by the co-administration. To understand the mechanism for
      the additive effects, induction of specific isozymes of cytochrome P450 involved
      in the activation of the mutagens was studied. Co-administration of BHT (0.1%)
      and flavone (0.1%) increased markedly the levels of proteins and the activities
      of the enzymes related to the isozymes of CYP2A and CYP2B, while co
      administration of BHA (0.2%) and flavanone (0.1%) elevated those related to
      CYP1A. Further, the activation of aflatoxin B1 and benzo[a]pyrene in hepatic
      microsomes was inhibited by the antibodies against these isozymes, which
      suggested that the enhanced activation of the mutagens by the co-administration
      might be mediated by the induction of these isozymes.

PMID- 9274803
TI  - Cytotoxicity and biotransformation inducing activity of rodent beddings: a global
      survey using the Hepa-1 assay.
AB  - Unknown and uncontrolled toxic materials in the environment of experimental
      animals endanger the reliability of research results. In this study, the
      cytotoxic and biotransformation inducer activity of beddings obtained from a
      number of institutes in Africa, Americas, Asia, Australia and Europe were
      compared using the Hepa-1 in vitro-assay. A great variation in both cytotoxicity
      and inducer activity was observed. Pine shavings beddings, commonly used all over
      the world appeared in general to be highly cytotoxic. Extracts of corn cob, rice
      hulls and straws, used in a few laboratories, were practically non-toxic. Some
      softwood extracts, especially from pine, were also potent inducers of cytochrome
      P4501A1. Grass as well as hardwood materials were much less active. Due to great
      variation in toxicity and inducer activity in the beddings it is possible that,
      in spite of standardization of feed and other environmental factors, different
      biological responses to chemicals and drugs in even genetically identical animal
      strains in different laboratories, may be obtained. Control of bedding, one of
      the animals' closest environmental factors, for its toxicity and
      biotransformation enzyme induction is strongly recommended.

PMID- 9274804
TI  - Peroxisome proliferators increase the formation of BPDE-DNA adducts in isolated
      rat hepatocytes.
AB  - Peroxisome proliferators are known to modulate the activity of xenobiotic
      metabolising enzymes, including glutathione S-transferase (GST) and cytochrome P
      450 (CYP). In this study the effect of peroxisome proliferators silvex and di(2
      ethylhexyl)phthalate (DEHP) on the formation of (+)-anti-benzo(a)pyrene -7,8
      dihydrodiol-9,10-epoxide (BPDE)-DNA adducts from a proximate mutagen and
      carcinogen (-)-transbenzo(a)pyrene-7,8-dihydrodiol (BPDD) has been investigated.
      Rat CYP1A1 metabolises BPDD to mutagenic BPDE, which may form DNA adducts or,
      alternatively, be detoxified by hydrolysis or glutathione conjugation. In this
      experiment the formation of BPDE-DNA adducts was significantly increased in
      hepatocytes isolated from all silvex treated rats and two out of four DEHP
      treated rats (14 day treatment). The activity of CYP1A1 was increased whereas GST
      was reduced by the peroxisome proliferator silvex. These changes were more
      significant than those induced by DEHP. We have hypothesised that the formation
      of BPDE-DNA adducts was primarily due to the increased BPDD activation to BPDE
      versus reduced detoxication of BPDE. Other hepatic changes induced by the
      peroxisome proliferators, e.g. peroxisome proliferation per se and increased
      mitotic activity of the liver could have an effect on the outcome of BPDD
      exposure.

PMID- 9274805
TI  - MPTP toxicity in rat striatal slices: dopamine uptake alteration does not appear
      to be related to lipid peroxidation.
AB  - 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which is used to create
      experimental models of parkinsonism, induces both dopaminergic neurotoxicity and
      peroxidation reactions. The present work investigated the interaction between the
      dopamine (DA) uptake system, lipid peroxidation and MPTP in a rat striatum slice
      model. [3H]DA uptake was decreased and the concentration of thiobarbituric acid
      reactive substances (TBARS) increased after a plain preincubation in Krebs-Ringer
      bicarbonate buffer for 150 min. The decrease in [3H]DA uptake and the increase in
      TBARS were suppressed by the iron-chelating agent desferrioxamine. Inhibition of
      [3H]DA uptake was intensified, [3H]GBR 12 935 binding to DA uptake sites was
      decreased and TBARS production was inhibited in slices after preincubation with
      MPTP. MPTP effects were inhibited by L-deprenyl, a MAO-B inhibitor. These results
      suggest that the spontaneous decrease in DA uptake during simple preincubation in
      pure Krebs-Ringer solution was related to spontaneous TBARS generation. During
      MPTP preincubation, alteration of the DA uptake mechanism was not due to
      additional lipid peroxidation since TBARS production was decreased. MPTP effects
      could have resulted from other events which are discussed.

PMID- 9274806
TI  - Sensory nerve-mediated inhibitory responses in airways of F344 rats.
AB  - We recently described a sensory nerve inhibitory system that mediates relaxation
      in the airways of Sprague-Dawley rats. Results of several studies have shown that
      this system protects the lungs against injury induced by toxic stimuli. Whether a
      similar inhibitory system exists in the airways of Fischer 344 (F344) rats is
      unknown. Because this rat strain is used extensively in lung toxicological
      research, the purpose of this study was to determine whether a sensory nerve
      inhibitory system exists in intrapulmonary bronchi and tracheae isolated from
      F344 rats. In intrapulmonary bronchi at resting tone, substance P (1.0 microM)
      evoked a transient contraction that was inhibited by the 5-HT2A receptor
      antagonist, ketanserin. Exposing airway segments to compound 48/80 to degranulate
      mast cells also abolished substance P-induced contractions. Inhibition of
      cyclooxygenase with meclofenamate augmented markedly the contraction to substance
      P in the intrapulmonary bronchi. In intrapulmonary bronchi that were contracted
      with bethanechol, substance P evoked a biphasic response characterized by an
      increase in tension above that induced by bethanechol followed by relaxation.
      Incubation of the airways with ketanserin abolished the contractile portion of
      the response; relaxation responses were augmented after ketanserin. In contracted
      intrapulmonary bronchi that had been treated with compound 48/80, substance P and
      capsaicin caused relaxation responses that were inhibited markedly or were nearly
      abolished by the NK1 receptor antagonist, RP67580, by meclofenamate, and by
      denuding the epithelium. Capsaicin-induced relaxation responses also were
      abolished by desensitization of C-fibers with capsaicin. Only ketanserin
      sensitive contractile responses were observed in response to substance P in
      tracheal segments. We conclude that a sensory nerve inhibitory system exists in
      the intrapulmonary airways of F344 rats. The presence of this inhibitory system
      in F344 rat airways may play a protective role against lung injury induced by
      inhaled toxicants.

PMID- 9274807
TI  - Relationships between cell density, glutathione and proliferation of A549 human
      lung adenocarcinoma cells treated with acrolein.
AB  - Acrolein is a highly electrophilic alpha,beta-unsaturated aldehyde to which
      humans are exposed in various situations. Acrolein reacts rapidly with and
      depletes cellular glutathione (GSH), and is toxic to various types of cells. In
      the current study, the ability of acrolein to alter proliferation of A549 cells
      was found to be dependent on cell density as well as total cell number. Thus,
      'doses' must be expressed per cell rather than as a concentration, and all
      related studies need to be performed by plating a constant number of cells. A549
      cells were plated at various densities and treated with acrolein after 48 h.
      Acrolein doses up to 47 fmol/cell at the time of treatment did not cause cell
      lethality. However, growth of A549 cells (as shown by thymidine incorporation,
      alamarBlue and total protein) was inhibited at acrolein levels > 34 fmol/cell in
      6-well plates seeded at 5000 cells/cm2 48 h prior to treatment. Cellular GSH
      levels were decreased 34% by 2 h at acrolein levels of 6.7 fmol/cell and by 65%
      at 47 fmol/cell. Recovery of GSH was rapid at 6.7-47 fmol/cell acrolein,
      returning to control levels or above by 12 h post-treatment. These data show a
      strong correlation between cellular GSH and proliferation. The apparent conflict
      with a previous study of Ramu et al., suggesting that sublethal concentrations
      (up to 10 microM) of acrolein inhibited the proliferation of A549 cells without a
      decline in total cellular GSH, arose because, while the acrolein concentration
      was the same in cells used for proliferation and GSH assays, GSH measurements
      were done in cells plated at a higher density, resulting in a much lower acrolein
      dose per cell. Interestingly, very low dose levels of acrolein with cells seeded
      at low densities stimulated cell growth despite an initial decline in GSH
      content. Preliminary studies with the stress genes hsp70 and gadd153 suggest that
      acrolein at 35 fmol/cell does not stimulate formation of their mRNA beyond the
      level stimulated by a 2 h incubation in serum-free medium but may actually delay
      or decrease the induced expression. The mechanism(s) of the inhibitory and
      mitogenic effects of acrolein remains to be determined, but could be due to
      changes in gene expression induced by this electrophile, perhaps mediated by
      changes in GSH.

PMID- 9274808
TI  - The cytotoxic effect of paraquat to isolated renal proximal tubular segments from
      rabbits.
AB  - Paraquat (PQ) induces lung, liver and kidney damage. Since PQ mainly is
      eliminated by the kidney, the kidney damage is of particular importance to the
      outcome of PQ poisoning. The exact toxic mechanism of PQ is still unclear but it
      is assumed to involve redox cycling and formation of reactive oxygen species. In
      this study, further investigations on the toxic mechanism and metabolic effects
      of PQ were performed using isolated renal proximal tubules from rabbits. Proximal
      tubules were isolated using a combined iron perfusion and collagenase method.
      Suspended tubules were incubated for varying periods and concentrations of PQ at
      25 or 37 degrees C in Krebs-Ringer phosphate buffer or HCO3-/CO2 buffer. The
      cytotoxic effect of PQ was evaluated by (1) markers of oxidative stress: status
      of glutathione (GSH/GSSG) and formation of malondialdehyde (MDA); and (2) markers
      of tubular metabolism: oxygen consumption (QO2), transport of 14C-p-aminohippuric
      acid (PAH) and 14C-tetraethylammonium (TEA). Using 0.5 and 5 mM PQ, the GSH/GSSG
      ratio decreased whereas formation of MDA increased indicating oxidative stress.
      PQ reduced the accumulation of PAH and TEA, the basal QO2 and the ouabain
      sensitive QO2 indicating inhibition of the Na/K-ATPase. Nystatin-stimulated QO2
      was reduced by PQ, excluding inhibition of Na+ entry as a possible cytotoxic
      mechanism and suggesting mitochondrial injury. This was confirmed by measuring
      FCCP-uncoupled QO2. Thus high concentrations of PQ appear to disrupt
      mitochondrial electron chain transfer resulting in reduction of metabolic
      functions.

PMID- 9274809
TI  - Lead exposure causes generation of reactive oxygen species and functional
      impairment in rat sperm.
AB  - The relationships between blood lead, sperm lead, sperm reactive oxygen species
      (ROS) level, and sperm fertile capability were investigated to understand the
      effects of lead exposure on sperm function and the mechanism of these effects.
      Male Sprague-Dawley rats, 7 weeks old, were randomly divided into control group
      and lead-treated group. The controls and lead-treated animals received
      intraperitoneal injection of 10 mg sodium acetate and 10 mg lead acetate/kg body
      weight, respectively, weekly for 6 or 9 weeks. The blood lead and epididymal
      sperm lead were analyzed by graphite furnace atomic absorption spectrophotometer.
      Chemiluminescence was measured to evaluate the generation of sperm ROS. Sperm
      oocyte penetration rate (SOPR) was measured to evaluate sperm function. After 6
      weeks of lead exposure, the rats had average blood lead levels of 32 microg/dl,
      sperm lead levels of 0.67 +/- 0.11 microg/10(9) sperm, unchanged epididymal sperm
      counts, percent of motile sperms, and motile epididymal sperm counts compared
      with control animals. However, after 9 weeks of lead exposure, the rats had
      average blood lead levels of 48.0 +/- 4.3 microg/dl, sperm lead levels of 0.88 +/
      0.16 microg/10(9) sperm, statistically lower epididymal sperm counts, and lower
      motile epididymal sperm counts. There was a good correlation between the blood
      lead and sperm lead(r2 = 0.946, P < 0.001). The sperms of lead-exposed rats
      produced significantly higher counts ofchemiluminescence than did those from the
      control rats (P < 0.001). The chemiluminescence counts were positively associated
      with sperm lead level (r2 = 0.613, P < 0.001). Epididymal sperm counts, motility
      and motile epididymal sperm counts were negatively associated with sperm
      chemiluminescence (r2 = 0.255, 0.152, and 0.299; P < 0.01, 0.05, and 0.01,
      respectively). The SOPR were positively associated with epididymal sperm counts,
      motility and motile epididymal sperm counts (r2 = 0.136, 0.285, and 0.264; P <
      0.05, 0.01, and 0.001, respectively). The sperm chemiluminescence was negatively
      associated with SOPR (r2 = 0.519, P < 0.001). It is concluded that lead exposure
      probably affected the sperm function by activating one of the pathways of ROS
      generation.

PMID- 9274810
TI  - Potential role for IL-5 and IL-6 in enhanced IgA secretion by Peyer's patch cells
      isolated from mice acutely exposed to vomitoxin.
AB  - Dietary exposure to vomitoxin (VT) results in hyperelevated serum IgA and IgA
      nephropathy in mice. To assess the possible role of cytokines in this IgA
      dysregulation, the effects of a single oral exposure in B6C3F1 male mice to 0, 5
      or 25 mg/kg BW VT on production of IgA and cytokines in Peyer's patch (PP) and
      spleen cell cultures were evaluated. IgA levels were increased significantly in
      PP cell cultures prepared from mice at 2 or 24 h after oral exposure to VT and
      subsequently stimulated with phorbol myristate acetate (PMA) and ionomycin (ION)
      or with lipopolysaccharide (LPS). Significant effects on IgA production were not
      observed in spleen cell cultures. Since cytokines such as IL-2, IL-4, IL-5 and IL
      6 have been shown to promote IgA production, the effect of the same VT exposure
      regimen on secretion of these mediators was determined in PP and spleen cultures.
      Supernatant IL-2 and IL-4 levels were unaffected by the prior treatment of
      animals with VT. In contrast, IL-5 levels were increased significantly in 7-day
      PP cell cultures obtained 2 h after VT exposure both with and without PMA + ION
      exposure but not in other cultures. IL-6 levels were increased significantly in
      LPS-treated cultures prepared from PP at 2 and 24 h following exposure to VT. IL
      6 levels were also elevated significantly in both PMA + ION or LPS treated
      cultures from spleen isolated at 2 h but not 24 h post VT exposure. To determine
      whether IL-5 or IL-6 play a role in IgA hyperelevation in vitro, PP and spleen
      cells from mice obtained 2 h after exposure to 25 mg/kg VT were cultured in the
      presence of neutralizing cytokine antibodies (Abs) and IgA production was
      monitored. Consistent with IL-5's previously documented role in IgA production,
      anti-IL-5 decreased IgA levels to background in cultures of both control and VT
      exposed PP or spleen cells in the presence of either PMA + ION or LPS. Similar
      results were seen with addition of anti-IL-6. IgA levels were decreased to a
      lesser extent in PP cells cultured with LPS and in spleen cells cultured with PMA
      + ION from VT-exposed mice to which anti-IL-2 Ab was added. Thus, the potential
      for enhanced IgA production exists in lymphocytes as early as 2 h and as late as
      24 h after a single oral exposure to VT and this may be related to the increased
      capacity to secrete helper cytokines of T cell and macrophage origin. Taken
      together, the results suggest that the superinduction of cytokine expression may,
      in part, be responsible for upregulation of IgA secretion in mice exposed orally
      to VT.

PMID- 9274811
TI  - A simple and efficient method for purification of prawn baculovirus DNA.
AB  - A new method for isolation of prawn baculovirus and subsequent extraction of
      viral DNA was developed. No density gradient centrifugation, ultracentrifugation
      or phenol-chloroform extraction steps were involved. Phenylmethylsulfonyl
      fluoride (PMSF) was used to prevent proteinase degradation, DNase and RNase were
      used to degrade prawn DNA and RNA respectively. The nucleocapsid was a
      bacilliform virion, about 58 62 nm in width and 300-350 nm in length as observed
      by transmission electron microscopy. Intact viral DNA was obtained by lysing
      nucleocapsids with guanidine hydrochloride and degrading protein with proteinase
      K. As the viral DNA was digested with restriction endonuclease and separated by
      electrophoresis, restriction fragments were clearly shown on the agarose gel. The
      size of the DNA was estimated approximately to be 290 kb. The virus which
      appeared to be a prawn baculovirus was named prawn white spot baculovirus (PWSBV)
      due to the white spots which appeared on the inside surface of the crust of
      infected prawns.

PMID- 9274813
TI  - Propagation of human astrovirus in the PLC/PRF/5 hepatoma cell line.
AB  - Astroviruses are associated with gastroenteritis in humans and many diseases in
      animals. Human astroviruses (HAstVs) cannot be propagated readily or isolated in
      conventional cell cultures. The presence of trypsin supports HAstV growth in
      selected cell cultures such as the continuous colonic carcinoma cell line (CaCo
      2). This study reports on the propagation of cell culture adapted reference
      strains of HAstV, and the direct isolation of HAstV from stool specimens in the
      human hepatoma cell line PLC/PRF/5.

PMID- 9274812
TI  - Procedures for reproducible detection of rabies virus antigen mRNA and genome in
      situ in formalin-fixed tissues.
AB  - Procedures allowing the reproducible in situ detection of rabies virus antigen
      and RNAs (both genome and message) in formalin-fixed tissue are described. These
      procedures can be used on sequential tissue sections and thereby permit
      comparison of results from tests detecting both antigen and RNA in the same
      tissue. This antigen-detecting procedure has also been used to identify both the
      phylogenetically distant rabies viruses from silver-haired bat and vampire bat
      and the rabies-related viruses Mokola, Duvenhage, and Lagos bat. One of the
      critical steps in these procedures is the digestion (and the resulting exposure
      of the target molecules) with proteinase K. These methods may be useful for the
      identification of other viruses of public health importance. Because in many
      situations only formalin-fixed tissue is available for postmortem diagnosis, the
      technical ability to identify a virus antigen and nucleic acid in such tissues
      greatly extends potential diagnostic capabilities.

PMID- 9274814
TI  - Booster immunization with a partially purified citrus tristeza virus (CTV)
      preparation after priming with recombinant CTV coat protein enhances the binding
      capacity of capture antibodies by ELISA.
AB  - Groups of rabbits and young lambs were immunized subcutaneously and
      intramuscularly with a recombinant citrus tristeza virus (CTV) coat protein (rCTV
      CP) antigen. Three weeks after primary immunization the animals were divided into
      two groups that were boosted either with rCTV-CP or with a partially purified
      preparation of CTV particles (ppCTV). Twelve and 15 days after the last
      injection, the animals were bled and the binding capacity of the antisera for CTV
      detection was examined for capture antibodies by the indirect ELISA. Considerably
      higher ELISA titers were obtained from animals that were boosted with ppCTV than
      with rCP. Boosting with partially purified native antigens after priming with
      recombinant antigens is expected to extend the applicability of the antisera for
      detecting other structural and non-structural viral antigens by trapping ELISA.

PMID- 9274815
TI  - An enzyme-linked immunosorbent assay to detect antibodies against glycoprotein gE
      of bovine herpesvirus 1 allows differentiation between infected and vaccinated
      cattle.
AB  - A blocking enzyme-linked immunosorbent assay (ELISA) was developed for detecting
      antibodies against glycoprotein gE (gE) of bovine herpesvirus 1 (BHV1). The assay
      is based on the use of two monoclonal antibodies directed against different
      antigenic domains on gE. Sera from uninfected cattle and cattle that had been
      repeatedly vaccinated with gE-negative marker vaccines scored negative, whereas
      sera from cattle naturally or experimentally infected with BHV1 field strains
      scored positive in the gE-ELISA. Antibodies against gE appeared in the serum
      around 11 days after infection. Cattle that were first vaccinated and then
      challenged, thus having less virus replication, also became gE-seropositive. The
      sensitivity and specificity of the gE-ELISA is high, and therefore the gE-ELISA
      is suitable for differentiating between infected cattle and vaccinated cattle
      with a gE-negative vaccine.

PMID- 9274816
TI  - Differentiation of the seven serotypes of foot-and-mouth disease virus by reverse
      transcriptase polymerase chain reaction.
AB  - A strategy for reverse transcriptase polymerase chain reaction (RT-PCR) using
      multiple primers was developed to detect and to differentiate the seven serotypes
      of foot-and-mouth disease virus (FMDV) simultaneously, quickly and accurately.
      The development of the test was carried out on virus isolates grown in tissue
      culture prior to cDNA synthesis and PCR using various sets of primers. Primers
      P33 and P32 were used for the consensus PCR to detect FMDV regardless of the
      serotype. Positive cDNA was assayed in two multi-primer PCR mixes containing type
      specific primers capable of distinguishing between the seven serotypes. The
      serotype-specific primers were selected to correspond to regions of the genome
      coding for parts of the VP1 polypeptide that is responsible for the antigenic
      diversity of the virus group. Multi-primer mix P33-P(A-C-O-ASIA 1) gave products
      of 732, 596, 402, 292 bp for the A,C,O and ASIA 1 serotypes, respectively, and no
      target products for South African Territories serotypes (SAT 1, SAT 2 and SAT 3).
      The multi-primer mix P33-P(A-C-O-ASIA 1) was also capable of detecting a mixture
      of two different serotypes. Multi-primer mix P1-P(SAT 1-3-2) gave products of
      246, 201 and 75 bp for the SAT 1, SAT 3 and SAT 2 serotypes, respectively, and no
      specific products for serotypes A, C, O and ASIA 1. This is the first PCR assay
      to be described that differentiates between the SAT serotypes of FMDV. The method
      has been applied to 25 cell-culture-derived isolates of the SAT serotypes of FMDV
      and the results were totally compatible with the standard techniques for FMDV
      detection and serotyping.

PMID- 9274817
TI  - A multicentre quality assessment study to monitor the performance of HIV-1 PCR.
AB  - Eleven German laboratories and one Swiss laboratory initiated a quality
      assessment study to evaluate the specificity and sensitivity of their polymerase
      chain reaction (PCR) for detection of HIV-1 DNA. Following its own PCR protocols,
      each laboratory tested a panel of ten coded samples consisting of cell pellets
      containing 0, 0.1, 1, 10, 10(2), 10(3) and 10(4) ACH-2 cells per 1.5 x 10(5)
      uninfected peripheral blood mononuclear cells. Of the twelve participating
      laboratories, three reported correct results for the dilution series as well as
      for uninfected specimens. One or more classification errors were recorded for 12%
      of the samples for which the diagnosis was expected to be positive or negative.
      Samples containing 10 copies of the target template were correctly reported by
      eleven of the twelve participants. The average sensitivity was 97%. The results
      of the study revealed no significant differences between the Amplicor kit and in
      house procedures. Most of the classification errors occurred in specimens from
      HIV-negative samples. Out of 36 negative samples, 5 were reported false positive,
      showing that contamination remains a problem for some laboratories, regardless of
      the PCR test performed. Careful laboratory techniques and internal as well as
      external quality control procedures will help avoiding carryover contamination.

PMID- 9274818
TI  - The detection of enteroviruses in large volume concentrates of recreational
      waters by the polymerase chain reaction.
AB  - A rapid and simple method was developed to detect enteroviruses in large-volume
      water samples. It relies on the adsorption of the virus capsids to silica
      particles under acidic conditions, allowing their recovery by relatively gentle
      centrifugation. Different reagents used in enterovirus concentration and
      detection were seeded with Coxsackievirus B5 and used to optimise the recovery
      method, which was then used to detect the enteroviruses from seeded and unseeded
      101 seawater samples in one PCR tube rather than in up to 50 sub-sample volumes,
      demonstrating its use for routine environmental monitoring. Concentrates from 36
      recreational water samples from three sites in N.E. England were analysed for
      enteroviruses by regular and the new method semi-nested PCR, and infectivity in
      cell culture. Some of the samples were also analysed for faecal indicator
      bacteria and F-specific bacteriophage. The results showed a marked increase in
      detection sensitivity when the whole sample concentrate was assayed as compared
      with a small volume aliquot.

PMID- 9274819
TI  - Neutralization titres of HIV-1-specific monoclonal antibodies vary according to
      the batch of primary human peripheral blood lymphocytes, but do not vary
      coordinately.
AB  - Human peripheral blood lymphocytes (PBL) were collected from five healthy adults
      under standard conditions and on a number of different occasions, and used in
      neutralization assays of human immunodeficiency virus type 1 (HIV-1) strain IIIB
      with three monoclonal antibodies (mAbs). Variations in neutralization titre were
      observed with different batches of PBLs with, for example, titres of ICR39.3b
      ranging from 1/10 to over 1/40000. However titres were as high, or higher, in
      PBLs than in C8166 cells (a human CD4+ T lymphoblastoid cell line) in 82% (28/34)
      of tests made. Most surprising was that neutralization by the three mAbs did not
      vary coordinately. In one batch of PBLs the neutralization titre of one of the
      mAbs might be increased while that of another mAb did not increase, or decrease.
      Thus PBLs could not be described as giving high or low levels of neutralization
      without reference to a specific mAb. This was not an assay problem as infectivity
      titres were relatively constant (varying by 1 to 1.4 fold with respect to C8166
      cells), and neutralization titres were reproducible with the same batch of frozen
      PBLs over a three month period. Only one donor gave consistently low
      neutralization titres (defined here as 1/200; 2/2 batches tested) with all three
      mAbs, but all other donors gave similarly low titres with one of their batches of
      PBLs. The non-coordinate variation in neutralization titre indicates the
      advisability of using antibodies of several different specificities in any kind
      of preventive or therapeutic immunity.

PMID- 9274820
TI  - Use of Epstein-Barr virus-transformed, autologous B-lymphoblastoid cells as
      antigen-presenting cells for establishment and maintenance of dengue virus
      specific, human cytotoxic T lymphocyte clones.
AB  - We have been maintaining dengue virus specific CD8+ cytoxic T lymphocyte (CTL)
      clones by repeated stimulation using autologous peripheral blood mononuclear
      cells (PBMC) as antigen presenting cells (APCs). In the present study, Epstein
      Barr virus (EBV)-transformed autologous lymphoblastoid cell lines (LCL) were
      compared with autologous PBMC as APCs for long term culture of a dengue virus
      specific, HLA class I-restricted CD8+ CTL clone CB2.8. We substituted autologous
      LCL for autologous PBMC and maintained CB2.8 for several months. CB2.8 cultured
      using LCL as APCs maintained antigen specific cytolytic activity. No demonstrable
      difference in the specificity or in the level of cytolytic activity against a
      panel of target cells was noted between the CB2.8 maintained with LCL and those
      maintained with PBMC. Lysis of the target cells was blocked by the anti-HLA-class
      I antibody indicating that HLA class I-restriction was also maintained. We then
      compared autologous LCL with autologous PBMC in the establishment of CD4 + CTL
      clones from the PBMC of a dengue-1 immune donor. Dengue 1-specific clones were
      derived from limiting dilution cultures using either type of APCs. Similar
      numbers of dengue virus-specific CD4+ CTL clones were established using LCL or
      PBMC as APCs. These results indicate that autologous LCL act as APCs for long
      term culture of virus-specific CTL clones and represent a cost effective
      alternative to repeated collection of PBMC.

PMID- 9274821
TI  - Diversity of the immunodominant epitope of gp41 of HIV-1 subtype O and its
      validity for antibody detection.
AB  - The immunodominant regions of the gp41 from 13 HIV-1 subtype O strains from
      Cameroon, 11 from France and one from Germany were sequenced. The amino acid
      sequences were compared to those of the 3 published HIV-1 subtype O isolates,
      ANT70, MVP-5180 and VAU. All HIV-1 subtype O isolates had a very conserved amino
      acid sequence in this region and showed a subtype O specific structure. Within
      the cysteine loop there was a positive charge of two basic amino acids, arginine
      and lysine. Only two strains (CM.6778 and CM.8161) showed an acidic amino acid in
      this loop. None of the isolates showed the same amino acid sequence in this
      immunodominant region. A 25 residue peptide from the immunodominant domain of
      gp41 of the MVP-5180 strain was synthesized, cycled to form the cysteine-loop and
      coated to microtiter plates. Antibody binding was detected by indirect ELISA
      using an enzyme labeled anti-human IgG. Out of 111 anti-HIV-1 positive specimens,
      collected mainly from Cameroonian HIV infected patients, only 10 were not
      reactive in this assay. The 42 anti-HIV-1 subtype O positive specimens gave all a
      reaction above cut off. Despite the diversity found in the amino acid sequences
      within the 25 isolates a peptide-based indirect ELISA representing the
      immunodominant epitope of the strain MVP-5180 successfully detected all the anti
      HIV-O sera so far tested, pointing to the importance of adding such a peptide for
      correct identification of HIV-1 subtype O infected patients, while some assays
      without HIV-O specific antigens partially fail to detect all anti-HIV-O
      specimens.

PMID- 9274822
TI  - Characterization of the double-stranded RNA genome segment S3 of avian reovirus.
AB  - The double-stranded RNA genome segment S3 of avian reovirus (ARV) S1133 was
      cloned following polyadenylation of both strands and cDNA synthesis of S3 RNA.
      The complete segment S3 nucleotide sequence was determined. S3 is 1196 base pairs
      long with one long open reading frame (ORF). The ORF possesses the AUG initiation
      codon in an optimum context for translation and starts at the first initiation
      codon (residue 24) and extends for 367 codons, sufficient to encode a protein of
      the same size as the known S3 gene product, protein sigmaB, one of the major
      outer capsid proteins of avian reovirus (Mr 41471). Protein sigmaB was
      subsequently expressed in Escherichia coli. The expressed protein sigmaB was
      indistinguishable from virion protein sigmaB as judged by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, immunoblot assay, and N-terminal amino acid
      sequencing of several peptides generated by Staphyloccus aureus V8 protease
      digestion. ARV S3 genome segment possesses a pentanucleotide UCAUC at the 3'
      terminus of its plus strand. The pentanucleotide sequence is common to the other
      genome segment S1 of ARV and to ten genome segments of mammalian reovirus at the
      3'-terminus of their plus strands. Amino acid sequence analysis revealed that ARV
      sigmaB does not contain a repeated basic amino acid motif as do the three
      serotypes of mammalian reovirus. The results of amino acid sequencing suggest
      that the most susceptible cleavage sites of sigmaB to V8 protease are located in
      a hydrophilic area between amino acids 95 and 140.

PMID- 9274823
TI  - Enhancement of immunohistochemical detection of HIV-1 p24 antigen in brain by
      tyramide signal amplification.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection of the brain has been
      demonstrated in formalin fixed, paraffin embedded post-mortem brain tissue (PM)
      by chromogenic immunohistochemistry for the HIV p24 antigen. The sensitivity of
      antigen detection is increased significantly by tyramide signal amplification
      (TSA) compared to the conventional peroxidase labelled Avidin-Biotin complex
      (ABC) technique. The TSA method also permitted the use of a lower concentration
      of primary antibody than is conventionally used. Sensitivity was enhanced further
      by microwave irradiation of the paraffin embedded tissues in citrate buffer. HIV
      1 p24 antigen was also detected in PM brain tissue by TSA enhanced
      immunofluorescence and demonstrated increased sensitivity compared to the
      conventional immunofluorescence technique with a greatly reduced autofluorescence
      background.

PMID- 9274824
TI  - Rapid isolation of double-stranded RNAs from entomopathogenic species of the
      fungus Paecilomyces using a commercial minicolumn system.
AB  - A method is described for rapid extraction of double-stranded RNAs from
      entomopathogenic fungi. Lyophilised and ground mycelium is incubated with 6 M
      guanidine thiocyanate, centrifuged, and the cleared lysate applied to a QIAGEN
      silica-based mini-spin column. Following washing with 70% isopropanol, bound
      nucleic acids are eluted under low salt conditions and treated with DNAse I prior
      to analysis by non-denaturing agarose gel electrophoresis.

PMID- 9274825
TI  - Neuronal activity in the frontal eye field of the monkey is modulated while
      attention is focused on to a stimulus in the peripheral visual field,
      irrespective of eye movement.
AB  - We tested the hypothesis that the frontal eye field (FEF) is involved in
      attention to the peripheral visual field (PVF). Neuronal activity was recorded in
      the FEF of two monkeys while they were performing three oculomotor tasks. In the
      visual attention task (VAT), the monkeys released a lever when a test stimulus
      (TS) presented in the PVF dimmed while they were looking at a central fixation
      point (FP). In the visual saccade task (VST), the monkeys exhibited saccadic eye
      movements when the FP was extinguished. In the visual fixation task (VFT), the
      monkeys released the lever when the FP dimmed. Overall, the activities of 80 FEF
      neurons were examined. The responses to visual stimuli of 41 of these neurons
      (51%) were modulated during the VAT. Twenty-five neurons showed pre-saccadic
      activity. Of these, 13 neurons (52%) exhibited activity modulation during the
      VAT. Eighteen neurons showed no pre-saccadic activity. Of these, 10 neurons (56%)
      exhibited activity modulation during the VAT. These results suggest that the FEF
      is involved in selecting the visual stimuli relevant to performing a task
      irrespective of eye movements.

PMID- 9274826
TI  - A novel near infra-red spectrophotometry system using microprobes: its evaluation
      and application for monitoring neuronal activity in the visual cortex.
AB  - A novel near-infrared (NIR) spectrophotometry system with microprobes of optical
      transmitter and receivers (550 and 410 microm in diameter, respectively) has been
      developed. A three-dimensional profile of the signal source estimated in in vitro
      experiments showed two spindle-shaped regions around the respective probes,
      suggesting that the signal detected by the present system comes from a relatively
      restricted region around each probe. Next, we examined how the concentration of
      oxygen in inspired gas affected the NIR signals in the rat cerebral cortex in
      vivo. Calculated concentrations of oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb)
      in the rat cortex changed in mirror-image fashion in response to the change in
      the O2 concentration in the inspired gas. Finally, NIR responses to visual
      stimulation were recorded from the striate cortex of conscious adult cats that
      had been monocularly deprived since the peak of the sensitive period.
      Corresponding to the results of previous electrophysiological studies,
      stimulation of the normal eye induced significant NIR signals, whereas that of
      the deprived eye evoked no response. These results indicate that this new NIR
      system can be applied to study changes in oxygen metabolism in relatively
      restricted regions following neuronal activation in the brain.

PMID- 9274828
TI  - Remyelination in the rat dorsal funiculus following demyelination by laser
      irradiation.
AB  - Excimer laser (KrF excimer laser, 248 nm wavelength) was used to damage cellular
      components in the dorsal funiculus at the lumbar level (L2) of the rat spinal
      cord. An open lesion was not found at the irradiation site on the spinal cord.
      However, the cytological examination revealed that cellular components were
      damaged to the depth of 200-500 microm from the pial surface. The characteristic
      feature was that at the border of the lesion, many axons remained naked but
      intact after their myelin sheaths had been completely disintegrated. Such naked
      axons were subsequently remyelinated by mature or immature glial cells. Mature
      oligodendrocytes, while retaining their cytoplasmic processes connected with the
      myelin sheaths of unaffected axons, extended new cytoplasmic processes on nearby
      naked axons and made new myelin sheaths around them. In contrast, 7 days after
      the irradiation, numerous immature glial cells appeared in association with naked
      axons, and some of them were differentiated into oligodendrocytes forming thin
      myelin sheaths on naked axons. These findings suggest that demyelinated axons can
      cause the proliferation and probably dedifferentiation of the oligodendrocyte
      lineage. The use of lasers provides a unique experimental model of demyelination
      and remyelination in the central nervous system of adult mammals.

PMID- 9274827
TI  - Effects of monocular enucleation on receptor binding and innervation pattern of
      the noradrenergic system in the superior colliculus of the pigmented rat.
AB  - To examine visual activity-dependent regulation of the central noradrenergic
      (NAergic) system, we carried out in vitro autoradiography for alpha2-, beta
      adrenergic and NMDA, non-NMDA glutamatergic receptors together with
      immunohistochemical analysis for dopamine beta-hydroxylase in the major central
      visual structures, including the lateral geniculate nucleus, superior colliculus
      (SC), and visual cortex of pigmented rats, that had received monocular
      enucleation. Beta-adrenergic receptor (beta-AR) binding in the SC contralateral
      to the enucleated eye was significantly decreased (82%, P < 0.01) following
      monocular deprivation started at P12 and continued for 2 or 11 weeks. No
      significant change in beta-AR binding was found in other structures examined. The
      number of varicosities in NAergic fibers was significantly increased following
      longer enucleation, i.e. for 11 weeks, in the contralateral SC (197%, P <0.001),
      whereas that in the ipsilateral SC was reduced (75%, P <0.001). Changes in alpha2
      adrenergic, NMDA, and non-NMDA glutamatergic receptor binding were small in these
      animals. Changes in neither beta-AR binding nor innervation pattern of NAergic
      fibers were found in one-year-old rats that had received a comparable period of
      monocular enucleation. Furthermore, neither unilateral ablation of the visual
      cortex to reduce a different set of major afferents nor neonatal enucleation,
      which induced anatomical reorganization of the afferents, was found to be
      effective. These findings suggest that beta-AR binding and innervation pattern of
      NAergic fibers in the SC are modified only when massive imbalance of retinal
      afferent activity is imposed during a limited period in early postnatal life
      (i.e. the sensitive period).

PMID- 9274829
TI  - Long-lasting enhancement of synaptic activity in dissociated cerebral neurons
      induced by brief exposure to Mg2+-free conditions.
AB  - The long-lasting enhancement of periodic clusters of spontaneous excitatory
      postsynaptic currents (SEPSCs) was examined in dissociated chick cerebral neurons
      that had been transiently exposed to Mg2+-free solution for 15 min. Since the
      enhancement was diminished by blockade of synaptic transmission, it clearly
      depended on synaptic activities. A specific antagonist of N-methyl-D-aspartate
      receptors (NMDARs) also inhibited the potentiations. Furthermore, the presence of
      inhibitors of protein and RNA synthesis in the Mg2+-free solution blocked the
      potentiation. In the potentiated neurons, the frequency of miniature excitatory
      postsynaptic currents (mEPSPs) increased. In addition, a diffusible molecule(s)
      that promoted the potentiation appeared to be involved in this phenomenon, since
      the conditioned medium of Mg2+-free treated neurons enhanced synaptic activity in
      other dish.

PMID- 9274831
TI  - Changes in the expression of novel Cdk5 activator messenger RNA (p39nck5ai mRNA)
      during rat brain development.
AB  - We previously reported that a neuron-specific Cdk5 activator, p35nck5ai, was most
      prominent in the newborn rat brain. In the adult brain, the expression decreased
      in most regions except hippocampus and primary olfactory cortex. A novel neuron
      specific Cdk5 activator, p39nck5ai, has been recently cloned. To clarify whether
      two activators were differentially distributed throughout brain development, in
      this study, we examined the spatial and temporal expression of p39nck5ai in the
      development rat brain. Northern blot analysis showed that p39nck5ai expression
      was low in 15-day old fetuses and newborn, and was most prominent in the 1-3 week
      old rat brains. In the adult rat brain, expression declined to the same level as
      in newborn rat brain. In situ hybridization showed that p39nck5ai mRNA was weakly
      expressed in all neurons of all regions in the newborn rat brain and the
      transcriptional level was highest in all regions in the 3 week-old rat brain. In
      the adult, expression was decreased in most neurons except Purkinje and granule
      cells in the cerebellum which retained high levels. These results suggest that
      p35nck5a and p39nck5ai may have different functional roles in distinct brain
      regions during different states of the rat brain development.

PMID- 9274830
TI  - Localization and gene expression of the receptor for pituitary adenylate cyclase
      activating polypeptide in the rat brain.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a recently
      identified member of the secretin/vasoactive intestinal polypeptide (VIP) family.
      There are at least two types of receptor for PACAP: type I (PACAPR), which
      specifically binds PACAP; and type II (VIP/PACAPR), which binds both PACAP and
      VIP. The localization of PACAPR in the rat brain was determined by in situ
      hybridization and immunocytochemistry. We raised antisera against a synthetic
      peptide that corresponds to the carboxy-terminal cytoplasmic domain which is
      found in all subtypes of PACAPR in order to localize PACAPR-like immunoreactivity
      (PACAPR-LI) in the rat brain. In general, the distribution of PACAPR-LI
      correlated well with the distribution of PACAPR transcripts. Particularly strong
      PACAPR mRNA expression was detected in the olfactory bulb, hippocampus,
      cerebellum and hypothalamus and moderate labeling was detected in other scattered
      regions. At the cellular level, PACAPR-LI appeared to be concentrated
      predominantly in neuronal perikarya and dendrites. At the ultrastructural level,
      strong immunostaining for the PACAPR was found in plasma membranes, rough
      endoplasmic reticulum, cytoplasmic matrix, and at synapses. This study provides
      the basis for a better understanding of the functions of PACAP in the rat brain.

PMID- 9274832
TI  - Trigeminal primary projection to the rat brain stem sensory trigeminal nuclear
      complex and surrounding structures revealed by anterograde transport of cholera
      toxin B subunit-conjugated and Bandeiraea simplicifolia isolectin B4-conjugated
      horseradish peroxidase.
AB  - Trigeminal primary afferent neurons were labeled by injecting the rat trigeminal
      ganglion with either wheat germ agglutinin-conjugated horseradish peroxidase (WGA
      HRP), cholera toxin B subunit (B)-HRP or Bandeiraea simplicifolia isolectin B4
      (IB4)-HRP. B-HRP stained medium to large cells (> 600 microm2), while IB4-HRP
      mostly small cells (< 400 microm2). WGA-HRP labeled trigeminal ganglion neurons
      of all sizes. Cell bodies in the mesencephalic trigeminal tract nucleus were
      labeled with WGA-HRP and B-HRP but not IB4-HRP. B-HRP revealed dense projection
      to the entire brain stem sensory trigeminal nuclear complex (BSTC) except for
      lamina II of the medullary dorsal horn (MDH). Some contralateral projection was
      also seen in the caudal part of MDH. Non-trigeminal nuclei receiving B-HRP
      labeled terminals included the paratrigeminal nucleus (paraV), solitary tract
      nucleus, supratrigeminal nucleus, Probst's nucleus and median accessory nucleus.
      Following IB4-HRP application, terminal label was found in more restricted
      regions within the BSTC. Modest terminal label was seen in the dorsal part of
      principal sensory nucleus and at the medial edge of subnucleus interpolaris,
      while relatively dense terminal fields were seen in the dorsal half of subnucleus
      oralis. The MDH laminae I and II contained dense terminal label. Non-trigeminal
      nuclei were almost devoid of the IB4-HRP-labeled terminals excepting the paraV
      that contained dense terminal label. The terminal areas revealed with WGA-HRP
      coincided with B-HRP-labeled and IB4-HRP-labeled areas combined.

PMID- 9274833
TI  - Machado-Joseph disease gene products carrying different carboxyl termini.
AB  - Three cDNA clones for the Machado-Joseph disease gene (MJD1) were isolated, two
      of which have a new exon sequence and a distinct 3' terminal nucleotide sequence
      resulting in a new carboxyl terminal domain in the translated product. The
      nucleotide sequence of the other one is similar to the previously published one
      except for five polymorphisms, one of which is a single nucleotide substitution
      resulting in a change from the stop codon (TAA; allele A) to a tyrosine residue
      (TAC; allele C). Genetic analysis results suggest that Japanese MJD mutations are
      associated with allele A.

PMID- 9274834
TI  - Beta2-Microglobulin dialysis amyloid and its formation: role of 3-deoxyglucosone
      and advanced glycation end products.

PMID- 9274835
TI  - The use of Mycophenolate Mofetil (Cellcept) in renal transplantation.
AB  - Mycophenolate Mofetil (MMF), the morpholinoethyl ester of the active compound
      mycophenolic acid, is a new immunosuppressive agent which blocks the de novo
      synthesis of guanine nucleotides. As this pathway is essential for purine
      synthesis of both T and B lymphocytes, the blocking effect on cell division is
      lymphocyte-selective with little effect on the division of other cell types. In
      three recent randomized multicenter trials, MMF in conjunction with ciclosporin
      and steroids has been shown to reduce the incidence of early acute rejection
      after renal transplantation by almost 50%. The toxicity profile is comparable to
      that of azathioprine but with a significantly higher efficacy. Major side effects
      are gastrointestinal with a slight increase of the incidence of mainly viral
      (CMV) infections. In contrast to ciclosporin and FK-506, MMF is not nephrotoxic.
      Future studies have to show whether the use of MMF in combination with other
      immunosuppressants may allow to reduce the doses of the most toxic ones. In
      addition, long-term studies are needed to prove its potential protective effect
      on the occurrence of chronic rejection as suggested by several experimental
      studies and by its effect on the incidence of acute rejection.

PMID- 9274836
TI  - Guidelines for looking at the antiphospholipid antibodies in systemic lupus
      erythematosus.
AB  - Lupus anticoagulant (LA), anticardiolipin (aCL), and/or antiphospholipid (aPL)
      antibodies are the hallmarks of the antiphospholipid syndrome, characterized by
      widespread thrombosis. The syndrome has been described as primary or secondary
      when aCL/aPL are the only classes of detectable autoantibodies or occur in the
      context of systemic lupus erythematosus (SLE) or SLE-like disease. However, since
      LA/aCL/aPL have been extensively looked for, it has become evident that they may
      also be detected in the absence of any clinical correlation with thrombosis. In
      particular, among SLE patients, these antibodies mean a high risk of thrombosis
      only in a small subset, sharing clinical features with primary antiphospholipid
      syndrome. As laboratory examination is still unable to distinguish between high
      risk and non-high-risk antiphospholipid antibodies, it is crucial to have some
      reasonable criteria able to guide the day-to-day clinical practice. We attempt to
      trace the following guidelines: (1) distinguish between transient and persistent
      LA/aCL/aPL results; (2) do not forget the LA phenomenon in the era of aCL/aPL;
      (3) maintain a strict communication with the laboratory; (4) exclude other causes
      of primary coagulation abnormalities; (5) look at the time of appearance of
      LA/aCL/aPL with respect to thrombosis; (6) analyze any possible laboratory clue
      putatively useful to distinguish between 'rouge' and 'non-rouge' LA/aCL/aPL; (7)
      look for signs of widespread noninflammatory vasculopathy; (8) do not engage a
      war to the knife against LA/aCL/aPL by immunosuppressive therapies.

PMID- 9274837
TI  - The renal hemodynamic response to an oral protein load is normal in IgA
      nephropathy.
AB  - The study was devised to explore the effects of an acute oral protein load on
      renal hemodynamic response in patients with IgA nephropathy (IgAN). The study was
      performed in 10 proteinuric IgAN patients (800 +/- 300 mg/day) and in 20 healthy
      controls (matched by sex, age, BMI, BSA, plasma creatinine, plasma urea, urinary
      urea and protein intake). Blood pressure and creatinine clearance were nearly
      identical in the two groups. GFR and RPF, measured as the clearance of inulin and
      of p-aminohippurate (PAH) were studied before and after a meat meal which
      provided 2 g of protein/kg BW. Following the protein load, renal reserve, percent
      renal reserve and postmeal cumulative changes of GFR were not significantly
      different in IgAN and controls. Filtration fraction (FF) at baseline was
      significantly higher (p < 0.01) in IgAN than in controls (25.5 +/- 1.41 vs. 19 +/
      2%). Postmeal hyperemia and hyperfiltration did not affect FF in either group.
      Filtration capacity in IgAN was lower (p<0.02) than in controls (117 +/- 5.6 vs.
      137.9 +/- 7.0 ml/min x 1.73 m2), whereas the percent of filtration capacity
      utilized at rest was identical in controls and in IgAN. Creatinine clearance
      overestimated GFR in IgAN. The data indicate that renal hemodynamic response to
      proteins in IgAN is normal.

PMID- 9274838
TI  - Renal functional response to protein loading in type 1 (insulin-dependent)
      diabetic patients on normal or high salt intake.
AB  - Insulin-dependent diabetes mellitus (IDDM) patients may have an increased
      intrarenal angiotensin II activity. In diabetic patients, captopril increases the
      renal hemodynamic response to an amino acid infusion. We investigated the effects
      of two salt diets on arterial pressure and renal response to a protein load in 10
      normotensive (blood pressure < 140/90 mm Hg) IDDM patients (aged 30 +/- 3 years)
      who had diabetes for 7 +/- 4 years and normoalbuminuria levels [albumin excretion
      rate 4.8 (2.5-19.1) microg/min]. After 1 week of normal (approximately 100
      mmol/day; approximately 100 mEq/l) and 1 week of high (approximately 300
      mmol/day; approximately 300 mEq/l) salt intake, renal hemodynamic studies were
      performed at baseline and after a protein load (meat meal) of 100 g/1.73 m2. The
      mean 24-hour urinary sodium excretion levels were 99 +/- 27 and 293 +/- 80 mmol
      (mEq) with normal and high salt intake, respectively. No significant changes were
      seen in plasma sodium and glucose control with the normal and high salt diets,
      respectively: plasma sodium 135 +/- 3 vs. 137 +/- 1 mmol/l (mEq/l), (p = 0.08)
      and glycated hemoglobin 9.1 +/- 1.9 vs. 9.4 +/- 2.1% (p = 0.36). The body weight
      (70.9 +/- 12 vs. 71.8 +/- 13 kg; p = 0.015) was significantly higher with a high
      salt diet. The mean arterial pressure was similar with both diets (normal vs.
      high salt diet 91 +/- 9 vs. 89 +/- 6 mm Hg, p = 0.25). The plasma renin
      concentration [28 +/- 15 vs. 16 +/- 6 microU/ml(168 +/- 90 vs. 96 +/- 36 pmol/l),
      p = 0.013] and angiotensin II [8.8 +/- 4.4 vs. 6.4 +/- 3.5 pg/ml (0.052 +/- 0.025
      vs. 0.038 +/- 0.021 nmol/l), p = 0.016] were significantly lower with the high
      salt diet. Following protein loading, the glomerular filtration rate increased
      with both diets: normal salt diet 114 +/- 26 vs. 128 +/- 30 ml/min/1.73 m2(1.9 +/
      0.43 vs. 2.13 +/- 0.50 ml/s/1.73 m2), p = 0.04; high salt diet 118 +/- 23 vs.
      127 +/- 29 ml/min/1.73 m2 (1.97 +/- 0.38 vs. 2.12 +/- 0.48 ml/s/1.73 m2), p =
      0.13. The change in renal plasma flow was similar to that of the glomerular
      filtration rate with normal and high salt intake, respectively: 566 +/- 94 vs.
      617 +/- 142 ml/min/1.73 m2 (9.44 +/- 1.57 vs. 10.29 +/- 2.37 ml/s/173 m2), p =
      0.0017; 572 +/- 125 vs. 600 +/- 110 ml/min/1.73 m2 (9.54 +/- 2.08 vs. 10.00 +/-
      1.83 ml/s/1.73 m2), p = 0.057. In this subset of normotensive normoalbuminuric
      IDDM patients, a high salt intake did not promote an exaggerated renal response
      to the protein load despite inhibition of the renin-angiotensin system.

PMID- 9274840
TI  - Glomerular ICAM-1 expression related to circulating TNF-alpha in human
      glomerulonephritis.
AB  - To clarify the in vivo involvement of cellular adhesion molecules and cytokines
      in human glomerulonephritis, we have investigated the glomerular and interstitial
      expression of intercellular adhesion molecule 1 (ICAM-1) in 69 kidney biopsy
      specimens by immunohistochemical methods and its correlation with serum bioactive
      tumor necrosis factor alpha (TNF-alpha) and soluble ICAM-1 (sICAM-1) levels in 43
      cases. In normal controls, glomerular ICAM-1 expression and serum TNF-alpha and
      sICAM-1 levels showed a mean score of 1.0 (n = 7) and were 12.1 +/- 1.5 and 187
      +/- 5 ng/ml (mean +/- SEM, n = 25), respectively. ICAM-1 was positive in 68
      kidneys except in 1 patient with membranous nephropathy at various degrees in
      glomeruli and in 72% of peritubular capillaries or venules in the interstitium.
      Serum-bioactive TNF-alpha levels increased in the patients with IgA nephropathy,
      purpura nephritis, and lupus nephritis (LN) (18.9 +/- 4.1, 32.6 +/- 13.3, and
      20.9 +/- 3.5 pg/ml) and were positively correlated with the grade of glomerular
      ICAM-1 expression (n = 43, r = 0.57, p < 0.001), endocapillary proliferation with
      exudative lesions (r = 0.72, p < 0.001) and hematuria (r = 0.62, p < 0.001).
      Serum sICAM-1 levels were elevated in patients with LN and purpura nephritis and
      decreased from 312 +/- 40 to 226 +/- 21 ng/ml after methylprednisolone pulse
      therapy in LN (n = 9, p = 0.0285). sICAM-1 levels were positively correlated with
      the grade of interstitial ICAM-1 expression (r = 0.46, p < 0.05), and sICAM-1
      levels (>210 ng/ml) showed high odds ratios in the interstitial ICAM-1-positive
      cases and systemic vasculitides such as purpura nephritis and LN (6.00, p =
      0.0355; 6.50, p = 0.0216, respectively). These results suggest that bioactive TNF
      alpha might relate to glomerular ICAM-1 expression associated with endocapillary
      lesions in human glomerulonephritis and that sICAM-1 levels may be used as a
      clinical marker to assess interstitial lesions in human nephritis and systemic
      vasculitides.

PMID- 9274839
TI  - Hemodialysis-induced upregulation of granulocyte adhesion molecules CD11b/CD18 is
      independent from 5-lipoxygenase activity.
AB  - Hemodialysis with new cuprophane membranes upregulates expression of granulocyte
      adhesion molecules and activates 5-lipoxygenase as reflected by the enhanced
      generation of leukotriene B4 (LTB4). We assessed the role of 5-lipoxygenase
      activity in hemodialysis-induced upregulation of the granulocyte adhesion
      molecules, CD11b and CD18, and granulocyte adhesion to human umbilical vein
      endothelial cells in an ex vivo dialysis model. 5-Lipoxygenase was effectively
      inhibited by preincubation of human whole blood with the specific inhibitor, BAY
      X1005. Dialysis with new cuprophane but not with new acrylonitrile membranes
      significantly upregulated expression of CD11b and CD18 by 6-fold and 4-fold,
      respectively. Inhibition of 5-lipoxygenase did not affect the expression of CD11b
      and CD18 during dialysis with either of the two membranes. In contrast to the
      enhanced expression of CD11b and CD18, adhesion of granulocytes to human
      umbilical vein endothelial cells did not increase during dialysis, nor was it
      affected by BAY X1005. These data indicate that ex vivo dialysis with cuprophane
      membranes upregulates expression of CD11b and CD18 on granulocytes independent of
      the activation of 5-lipoxygenase.

PMID- 9274841
TI  - High prevalence of myocardial ischemia and vasoconstrictive hormonal release in
      hypertension during chronic renal failure.
AB  - OBJECTIVE: Indexes of myocardial ischemia and vasoconstrictive hormonal release
      were evaluated in order to investigate the difference between essential
      hypertension and hypertension during chronic renal failure. BACKGROUND: Arterial
      hypertension induces several cardiovascular alterations that reflect themselves
      either on the heart and/or on the coronary blood flow enhancing the
      cardiovascular risk. Since chronic renal failure can influence the neuroendocrine
      response, various mechanisms involved in hypertension during chronic renal
      failure are still unclear. High endothelin 1 (ET-1) levels have been found both
      in arterial hypertension and during chronic renal failure. Interestingly, either
      ET-1 or catecholamines seem also to be implied in the pathogenesis of myocardial
      ischemia. METHODS: 20 hypertensive uremic and 20 essentially hypertensive
      patients underwent echocardiographic wall motion and wall thickening analysis
      performed at baseline and immediately after the end of exercise. Simultaneously,
      myocardial perfusion was evaluated by 99mTc-MIBI-SPECT. In addition, plasma
      norepinephrine and ET-1 concentrations were measured at baseline and at peak
      exercise. RESULTS: The segmental radionuclide analysis showed a greater ischemic
      degree in hypertensive uremic patients. Yet, we were able to identify one or more
      regions of the left ventricle in which both systolic thickening measurements and
      wall motion after exercise were impaired. After exercise, wall thickening
      impairment was correlated with both wall motion abnormalities (r = 0.72, p <
      0.01) and MIBI ischemic grade (r = 0.82, p < 0.001). Basal and after-exercise
      plasmatic norepinephrine and endothelin levels were higher in hypertensive uremic
      than in essentially hypertensive patients. Moreover, there was a significant
      correlation between increments in norepinephrine concentration and MIBI perfusion
      defects, and between the increment in ET-1 concentration and both MIBI perfusion
      defects, or kinetic alterations assessed by wall motion as well as by wall
      thickening. CONCLUSIONS: This is the first cross-sectional study in which a
      higher degree of myocardial ischemia has been observed in hypertensive uremic
      patients combined with an enhanced plasma release of both norepinephrine and ET
      1. This phenomenon may contribute to enhance the cardiovascular risk of these
      patients.

PMID- 9274843
TI  - Ultrastructural study of glomerular capillary loops at different perfusion
      pressures as revealed by quick-freezing, freeze-substitution and conventional
      fixation methods.
AB  - Wistar rat kidneys were perfused with some fixatives at different pressures of
      100, 150, 200 or 250 cm H2O via the aorta and were studied by the quick-freezing
      and freeze-substitution (QF-FS) or deep-etching (QF-DE) methods, in addition to
      the conventional immersion or perfusion fixation method. Different parts of
      glomerular capillary walls were selected for morphometric analyses. It was
      demonstrated that the widths of glomerular slit diaphragms and the spaces between
      foot processes were more widely dilated at higher perfusion pressures (200 and
      250 cm H2O) than those seen at both normal perfusion pressure (150 cm H2O) and
      lower perfusion pressure (100 cm H2O). On the other hand, the glomerular basement
      membranes were thinner at higher perfusion pressures. By the QF-FS and QF-DE
      methods, the foot processes showed different shapes from those revealed by the
      conventional preparation methods, even at the same perfusion pressure. It is
      concluded that the widths of glomerular slit diaphragms and glomerular basement
      membranes and the spaces between foot processes may be significantly changed in
      vivo, depending on the hemodynamics in the glomerular capillary.

PMID- 9274842
TI  - Reevaluation of anionic sites in the rat glomerular basement membrane.
AB  - We reevaluated the distribution of anionic sites in the glomerular basement
      membrane with ruthenium red, alcian blue, cationic ferritin, polyethyleneimine,
      and cationic colloidal gold. Without the accentuation by the metal staining with
      uranyl acetate and lead citrate, we observed the existence of anionic sites
      throughout all the layers of the glomerular basement membrane with a similar
      reticular pattern and the structural difference between the lamina rara and
      lamina densa, indicating that the lamina rara is an actual structural element.

PMID- 9274844
TI  - Effects of indapamide on Ca2+ entry into vascular smooth muscle cells.
AB  - Part of the antihypertensive action of indapamide has been attributed to a direct
      inhibitory action on Ca2+ entry into vascular smooth muscle cells. The present
      study has been performed to identify the possible mechanisms involved. To this
      end the effect of indapamide on intracellular Ca2+ activity - [Ca2+]i - has been
      tested under control conditions and under conditions known to increase [Ca2+]i
      such as osmotic cell swelling (mimicking mechanical stress), depolarization
      (increase of extracellular K+ concentration) and oxidative stress (H2O2).
      Indapamide (10 micromol/l) was without effect on control [Ca2+]i, but
      significantly blunted the increase of [Ca2+]i following potassium-induced
      depolarization or following osmotic cell swelling. It did not significantly
      modify the increase of [Ca2+]i induced by H2O2. The effects on cell membrane
      potential induced by increased [K+], osmotic cell swelling, or H2O2 were not
      significantly modified by indapamide (10 micromol/l). Voltage-gated Ca2+ currents
      were not significantly modified by 10 micromol/l indapamide, but were
      significantly reduced by 100 micromol/l and blunted by 1 mmol/l. In conclusion,
      indapamide at high concentrations (100 micromol/l) inhibits voltage-gated Ca2+
      channels, an effect which blunts the increase of [Ca2+]i during depolarization of
      the cell membrane at increased extracellular [K+] or osmotic stress. Whether
      these effects at high concentrations of indapamide are relevant to the
      antihypertensive action, however, cannot be established from these in vitro
      studies.

PMID- 9274846
TI  - Derangement of pH homeostasis in the renal papilla: ochratoxin A increases pH in
      vasa recta blood.
AB  - It is reported that ochratoxin A (OTA) impairs urinary acidification by
      increasing the urinary pH and also increases the intracellular pH in Madin-Darby
      canine kidney cells. This study was designed to examine whether OTA deranges pH
      homeostasis in the interstitium (or vasa recta) of the renal papilla. Rats were
      injected once with OTA (3 micromol/kg body weight) intravenously (acute
      application) or with OTA (1.25 micromol/kg body weight/day) intraperitoneally for
      6 days (subchronic application). We measured the pH values in both the descending
      and ascending vasa recta blood (VR) in the renal papilla. Both the acute and
      subchronic applications of OTA led to significant increases in pH values in both
      descending and ascending VR by 0.4-0.6 pH units. However, no significant
      increases in pH values in renal arterial and aortic blood in OTA-treated rats
      were observed. We also examined the pH changes in collecting-duct urine after OTA
      injection (3 micromol/kg body weight). We found a significant increase in pH
      values 30 min after OTA injection; this significant elevation of pH values was
      present during the whole experiment (120 min). The results of this study suggest
      that OTA deranges pH homeostasis in the interstitium of the renal papilla, in
      addition to the impairment of urinary acidification.

PMID- 9274847
TI  - Magnetic resonance imaging of the kidney in hemorrhagic fever with renal
      syndrome: its histopathologic correlation.
AB  - We present 2 cases of magnetic resonance imaging in hemorrhagic fever with renal
      syndrome and their histopathologic findings. The low signal intensities along the
      renal outer medulla in T2-weighted images are persistent ex vivo as well as in
      vivo, and these are the radiologic counterpart of medullary congestion and
      hemorrhage. We will discuss the significance of the imaging in the fields of the
      medical renal disease such as acute renal failure and review the mechanisms of
      acute renal failure in hemorrhagic fever with renal syndrome.

PMID- 9274845
TI  - Renal effects of an angiotensin II antagonist in stroke-prone spontaneously
      hypertensive rat.
AB  - We evaluated the renal effects of the new angiotensin II type 1 (AT ) receptor
      antagonist, HR 720, in the stroke-prone spontaneously hypertensive rat. Rats were
      treated with either vehicle, HR 720, MK-954 (a selective AT1 receptor antagonist)
      or enalapril for 6 weeks. Blood pressure was decreased to a similar extent by HR
      720, MK-954 and enalapril (203 +/- 4, 202 +/- 5 and 190 +/- 4 vs. 247 +/- 4 mm Hg
      for control). Urinary protein secretion was also decreased (5.2 +/- 0.3, 5.3 +/-
      0.2 and 5.5 +/- 0.6 vs. 25.2 +/- 4.6 mg/100g/24h). The glomerular hypertensive
      change was improved in each drug-treated group (2.0 +/- 0.2, 3.3 +/- 0.3 and 1.6
      +/- 0.1 vs. 17.6 +/- 1.5%; p < 0.0001). These results show that, in addition to
      its antihypertensive effect, HR 720 has a beneficial effect on renal function.

PMID- 9274849
TI  - Orellanus syndrome: a rare cause of uremia.

PMID- 9274848
TI  - Recurrent hemolytic uremic syndrome with hypocomplementemia and intestinal
      lymphangiectasia.
AB  - A 23-year old male patient had eight distinct episodes of hemolytic uremic
      syndrome (HUS) between 8.5 and 15 years of age, five of them accompanied by
      hypocomplementemia. In the further course, severe hypertension, renal
      insufficiency as well as protein-losing enteropathy due to intestinal
      lymphangiectasia developed, whilst hypocomplementemia persisted. The association
      of recurrent HUS with hypocomplementemia and intestinal lymphangiectasia may
      represent a new association within a subgroup of the atypical HUS.

PMID- 9274850
TI  - Blood monitoring of bezafibrate in a chronic hemodialysis patient.

PMID- 9274851
TI  - Effect of oral adsorbent on the progression of diabetic nephropathy.

PMID- 9274852
TI  - Hemolytic-uremic syndrome associated with pseudomembranous colitis caused by
      Clostridium difficile.

PMID- 9274853
TI  - Prevention of cerebral edema and infarct in cerebral reperfusion injury by an
      antibody to interleukin-8.
AB  - Reperfusion after a transient ischemia is a frequently encountered clinical
      condition that often causes greater tissue damage than persistent ischemia
      itself. Reperfusion to rabbit brain, after a transient focal ischemia, induced
      neutrophil infiltration and aggregation--neither of which were observed in rabbit
      brain rendered ischemic alone for the same time interval--thereby leading to
      severe brain edema and infarct. Brain tissue levels of interleukin-8 (IL-8), a
      potent neutrophil chemotactic cytokine (chemokine), increased significantly at 6
      hours after reperfusion, but without a noticeable elevation of plasma IL-8
      levels. Moreover, we detected IL-8 protein immunohistologically in the vascular
      wall and, to a lesser degree, in infiltrated neutrophils, suggesting a local
      production of IL-8 in reperfused brain tissues. Furthermore, a neutralizing anti
      IL-8 antibody significantly reduced brain edema and infarct size in comparison to
      rabbits receiving a control antibody. These results implicate locally produced IL
      8 as a pivotal mediator of cerebral reperfusion and suggest that IL-8 is a novel
      target for the intervention of this injury.

PMID- 9274855
TI  - Renal tubular hyperplasia, polycystic disease, and glomerulosclerosis in
      transgenic mice overexpressing hepatocyte growth factor/scatter factor.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) has been implicated as a
      renotrophic agent, capable of stimulating renal regeneration after unilateral
      nephrectomy or acute kidney failure. However, evaluation of the therapeutic
      utility of HGF/SF requires thorough analysis of its effects in an appropriate in
      vivo model system. To this end, the renal structure and function in HGF/SF
      transgenic mice were examined. Mice overexpressing HGF/SF in the kidney and serum
      demonstrated prominent tubular cystic disease and progressive glomerulosclerosis,
      and were susceptible to premature death from renal failure. The tubular phenotype
      appeared to result from HGF/SF-Met autocrine stimulation of the tubular
      epithelium and consequent hyperplasia. Electron microscopic examination of
      glomeruli, which also showed enhanced cellular proliferation, revealed
      ultrastructural features consistent with focal segmental glomerulosclerosis: an
      increase in mesangial matrix, effacement of foot processes, and thickening of
      basement membrane. These changes were not present at birth but developed
      progressively with age, which is consistent with the notion that HGF/SF may not
      be essential for the early stages of nephrogenesis, but may play an important
      role in renal epithelial renewal and regeneration. Thus, HGF/SF transgenic mice
      could be a useful model for dissecting the molecular mechanisms leading to
      polycystic disease and focal segmental glomerulosclerosis. Moreover, our results
      suggest that caution should be used when considering HGF/SF as a future
      therapeutic agent.

PMID- 9274854
TI  - Glycodelins GdA and GdS modified by 3-hydroxyphthalic anhydride inhibit gp120-CD4
      binding and HIV-1 infection in vitro.
AB  - Bovine beta-lactoglobulin chemically modified with 3-hydroxyphthalic anhydride
      (3HP) was recently shown, at nanomolar concentrations, to block the binding site
      on CD4 for the HIV surface glycoprotein (gp120), potentially inhibiting HIV
      transmission. Human glycodelin has sequence homology with bovine beta
      lactoglobulin and appears as different glycoforms in endometrium (GdA) and
      seminal plasma (GdS). We studied the anti-HIV effects of chemically modified GdA
      and GdS on both the infection of MT-2 cells by HIV-1IIIB, and the infection of
      peripheral blood mononuclear cells by the primary HIV isolate THA/93/051
      belonging to subtype E. Whereas the native proteins were inactive when tested at
      physiologic concentrations, nanomolar concentrations of either 3HP-GdA or 3HP-GdS
      inhibited the production of HIV nucleocapsid p24, cytopathic effects of HIV
      1IIIB, and infection of peripheral blood mononuclear cells by the primary HIV
      isolate THA/93/051. Moreover, both modified proteins inhibited gp120-CD4 binding,
      3HP-GdS being more potent than 3HP-GdA (p = 0.0042). Because GdA and GdS have the
      same major protein core, the observed difference in gp120-CD4 binding must depend
      on the specific glycoform. In view of the previously reported contraceptive
      activity of GdA, the observed anti-HIV activity induced by its chemical
      modification should be of special interest in the development of antiviral
      strategies that may also have contraceptive effects.

PMID- 9274856
TI  - Transformation in vitro of a nontumorigenic rat urothelial cell line by tumor
      necrosis factor-alpha.
AB  - Chronic inflammation is a significant risk factor for the development of urinary
      bladder cancer. We showed previously that inflammation induced by killed
      Escherichia coli strikingly enhanced N-methyl-N-nitrosourea (MNU)-initiated rat
      bladder carcinogenesis. We also demonstrated a marked increase in several
      cytokines, including TNF-alpha, in aspirates from bladders treated with killed E.
      coli. In the present investigation, we tested the hypothesis that TNF-alpha
      released during inflammation was causally related to the development of bladder
      cancer. Using growth in soft agar and tumorigenicity in athymic nude mice as
      indices of transformation, we examined the effect of TNF-alpha on the enhancement
      of H2O2-initiated transformation of MYP3 cells; MYP3 is an anchorage-dependent
      nontumorigenic rat urothelial cell line. We have already demonstrated that H2O2
      is a potent transforming agent which is released during the inflammatory process.
      MYP3 cells pretreated with H2O2 were exposed to TNF-alpha (0 to 100 ng/ml) for 1
      week in monolayer culture and were then subjected to growth in soft agar. A
      marked increase in the number of colonies was observed in the cells that were
      first treated with H2O2 and subsequently exposed to TNF-alpha, as compared with
      the untreated control (p < 0.001). In addition, treatment with TNF-alpha alone
      caused colony formation and was associated with a 6.5- to 8.7-fold increase in
      intracellular H2O2 (p < 0.001). Addition of an antioxidant, alpha-tocopherol,
      resulted in a significant reduction in the number of colonies induced by TNF
      alpha (p < 0.001). The transformants induced by TNF-alpha have acquired the
      potential of anchorage-independent growth and tumorigenicity in athymic nude
      mice. Our results suggest that TNF-alpha-induced transformation in urothelial
      cells is due to induction of H2O2, and that this may be one of the mechanisms
      involved in the carcinogenesis in vivo associated with chronic urinary tract
      infection.

PMID- 9274857
TI  - Induction and nuclear translocation of thioredoxin by oxidative damage in the
      mouse kidney: independence of tubular necrosis and sulfhydryl depletion.
AB  - Adult T-cell leukemia-derived factor (ADF), originally defined as an interleukin
      2 receptor inducer, is a human thioredoxin (TRX). ADF/TRX is a conserved
      multifunctional reductant presumably associated with redox regulation of the
      cellular environment; it works in vitro as a cytokine, free radical scavenger,
      activator of transcription factors, and substrate for several enzymes. In the
      present series of experiments, we studied the expression and intracellular
      localization of ADF/TRX in mouse kidney from two different renal tubular injury
      models: a free radical-associated model with ferric nitrilotriacetate (Fe-NTA)
      and a free radical-independent model with HgCl2. Markers of oxidative damage,
      such as 8-hydroxy-2'-deoxyguanosine, thiobarbituric acid-reactive substances, and
      4-hydroxy-2-nonenal-modified proteins, were significantly increased in kidney
      from male C57B/6 mice 1 hour after a single intraperitoneal injection of Fe-NTA
      (5 mg iron/kg). However, in kidney from mice given a subcutaneous injection of
      HgCl2 (5 mg Hg/kg), none of these markers were increased, despite tubular
      necrosis with sulfhydryl depletion. In the Fe-NTA model only, Northern and
      Western blot analyses of the kidney revealed induction of ADF/TRX (> 2.5-fold)
      after 16 hours and translocation of ADF/TRX from the cytoplasmic to nuclear
      fraction (> 3.5-fold) after 24 hours. Immunohistochemistry showed a patchy
      distribution of ADF/TRX in the normal renal proximal tubules. In ex vivo
      experiments using serial normal kidney frozen sections, it was found that renal
      proximal tubules with low expression of ADF/TRX were more vulnerable to oxidative
      stress mediated by Fe-NTA. Collectively, these data suggest that: (a) ADF/TRX is
      induced and translocated to nuclei by oxidative damage mediated by Fe-NTA in the
      renal proximal tubules; (b) induction of ADF/TRX is independent of tubular
      necrosis or sulfhydryl depletion; and (c) ADF/TRX is involved in the cellular
      defense mechanisms in vivo against oxidative damage.

PMID- 9274858
TI  - Cerebrovascular smooth muscle cells internalize Alzheimer amyloid beta protein
      via a lipoprotein pathway: implications for cerebral amyloid angiopathy.
AB  - Cerebral amyloid angiopathy (CAA) is caused by the cerebrovascular deposition of
      Alzheimer amyloid beta protein (Abeta) and shows an increased incidence in
      carriers of the apolipoprotein E (APOE) epsilon4 genotype. To study the
      pathogenesis of CAA, primary cultures of human and canine smooth muscle cells
      from leptomeningeal vessels were incubated with fluorescein- and biotin
      conjugated amyloid beta-protein. In the presence of human serum or cerebrospinal
      fluid, A beta1-40 and Abeta1-42 were rapidly internalized and appeared within
      endosomal and lysosomal vesicles. The accumulation of intracellular Abeta was
      enhanced by chloroquine and blocked by cycloheximide and brefeldin A and
      pretreatment with trypsin, suggesting that the internalization of Abeta occurs by
      receptor-mediated endocytosis. The internalization of Abeta was also inhibited by
      lipoprotein-deficient serum or by incubation with the 39-kd receptor-associated
      protein, indicating that Abeta is internalized via a receptor of the low-density
      lipoprotein receptor family. A lipoprotein pathway was confirmed by
      colocalization of cell surface-bound or internalized Abeta with APOE and low
      density lipoprotein receptor-related protein. We propose a pathogenetic model of
      CAA, in which Abeta-APOE-complexes contained within the cerebrospinal fluid or
      the extracellular fluid of the brain are internalized and accumulated in
      cerebrovascular smooth muscle cells. Such a model could explain the preferential
      localization of CAA to the outer and middle layers of cortical and leptomeningeal
      arterioles, while indicating a mechanism by which the APOE genotype might
      determine the risk of CAA.

PMID- 9274859
TI  - Relationship between the cellular distribution of the alpha(v)beta3/5 integrins
      and adenoviral infection in salivary glands.
AB  - This study compared the localization of the alpha(v)beta3/5 integrins in the
      different cell types of the rat submandibular gland with the susceptibility of
      these cells to infection by an intraductally administered replication-deficient
      recombinant type 5 adenovirus coding for rat aquaporin 5 (termed AdrAQP5). We
      used a panel of antibodies and immunohistochemical procedures to determine the
      luminal membrane distribution of the integrins. The alpha(v)beta3/5 integrin
      subunits were present in luminal membranes of all ductal cell types and acini;
      however, the alpha(v) subunit was found to a lesser extent in the acini. After
      AdrAQP5 infection, the expression of AQP5 exhibited a similar, though not
      identical, cellular localization to that seen for alpha(v)beta3/5 integrins.
      AdrAQP5 infected all cell types in these glands, except excretory ducts, after
      intraductal administration, directing the transient expression of AQP5. In
      addition, the localization of alpha(v)beta3/5 integrins was examined in rabbit,
      monkey, and human submandibular and parotid glands. Although there were some
      interspecies differences, glands generally displayed the presence of these
      integrin subunits on luminal membranes of ductal cells and most acinar cells.
      These findings show that the presence of alpha(v)beta3/5 integrins on the luminal
      membranes of rat salivary epithelial cells is associated with the susceptibility
      of these cells to act as targets for adenoviral-mediated gene transfer. However,
      the abundance of alpha(v)beta3/5 integrin expression was not necessarily
      predictive of the extent of transgene expression in a particular cell type.
      Furthermore, because the salivary glands of rabbits, monkeys, and humans show a
      similar luminal membrane distribution of these integrins, it is likely that
      recombinant type 5 adenoviruses may be able to mediate in vivo gene transfer to
      salivary glands in these species.

PMID- 9274860
TI  - Expression of costimulatory molecules B7-1 and B7-2 in macrophages and granulomas
      of Crohn's disease: demonstration of cell-to-cell contact with T lymphocytes.
AB  - The pathogenesis of Crohn's disease, an intractable inflammatory disease,
      involves impaired and/or excessive activation of mucosal macrophages and T
      lymphocytes. B7-1 (CD80) and B7-2 (CD86) molecules are costimulatory molecules
      that are indispensable to T-cell activation by antigen-presenting cells. To
      elucidate the roles and characteristics of these antigen-presenting cells in
      Crohn's disease, in situ localization of B7-1 and B7-2 (in relation to the
      distribution of T cells) was clarified by light and electron microscopic
      immunohistochemistry. The results were compared with those from a study of
      ulcerative colitis. Normal colonic tissue expressed B7-1 or B7-2 only
      sporadically. In active Crohn's disease, however, an increase in the number of B7
      1/B7-2+ cells correlated with an increase in expression of HLA-DR and
      intercellular adhesion molecule-1. Most B7-1/B7-2+ cells were identified as
      noncaseating granulomas or as macrophages, which tended to form an aggregate
      especially in ulcer bases. In active ulcerative colitis, the increase of B7-1/B7
      2+ cells was not as prominent as that in Crohn's disease. Double
      immunohistochemistry revealed a close cellular distribution between noncaseating
      granulomas and T cells. Immunoelectron microscopy confirmed the expression of B7
      1/B7-2 along the plasma membranes of cytoplasmic processes of granuloma cells,
      where lymphocytes were closely attached. The present study suggested that
      granuloma formation in Crohn's disease is coupled with antigen presentation via a
      B7-1/B7-2-CD28 pathway, which may contribute to the pathogenesis of the disease.

PMID- 9274861
TI  - Production of macrophage inflammatory protein-1alpha by human mast cells:
      increased anti-IgE-dependent secretion after IgE-dependent enhancement of mast
      cell IgE-binding ability.
AB  - The contributions of mast cells to the pathology of allergic diseases, as well as
      to the expression of immunoglobulin E (IgE)-dependent host responses to
      parasites, reflect both the amounts and types of cytokines and other mediators
      that are released by these cells in such settings. Whereas mast cells cannot
      intrinsically express immunologically specific functions, the binding of IgE to
      high-affinity IgE receptors (Fc epsilonRI) on the surface of mast cells primes
      these cells to secrete cytokines and other biologically active products upon
      subsequent exposure to specific antigens. We now report that both HMC-1, a growth
      factor-independent human mast cell leukemia cell line, and growth factor
      dependent human umbilical cord blood-derived mast cells can secrete the
      multifunctional C-C chemokine, macrophage inflammatory protein-1alpha (MIP
      1alpha). In addition, we found that in vitro exposure of human umbilical cord
      blood-derived mast cells to concentrations of IgE within the range observed in
      the serum of subjects with allergic diseases or parasite infections, which
      markedly up-regulates the ability of these cells to bind IgE to their surface,
      also significantly enhances the ability of the cells to secrete MIP-1alpha upon
      subsequent passive sensitization with IgE and challenge with anti-IgE. Thus, IgE
      dependent enhancement of human mast cell IgE-binding ability permits these cells
      to respond to Fc epsilonRI-dependent challenge with significantly increased
      secretion of MIP-1alpha, a chemokine that can have diverse functions in
      inflammation, allergic reactions, and host responses to infection.

PMID- 9274862
TI  - Characterization of Trypanosoma brucei pyridoxal kinase: purification, gene
      isolation and expression in Escherichia coli.
AB  - Pyridoxal kinase catalyzes the ATP-dependent phosphorylation of vitamin B6,
      generating pyridoxal-5'-phosphate, an important cofactor for many enzymatic
      reactions. Pyridoxal kinase was purified 4300-fold to homogeneity from
      Trypanosoma brucei and peptides generated by proteolysis were subjected to amino
      acid sequence analysis. The peptide sequence information was used to generate a
      partial clone of T. brucei pyridoxal kinase by polymerase chain reaction (PCR),
      which in turn was used to screen a T. brucei genomic library for a full length
      clone. The 903-bp gene was sequenced and found to encode a 300-amino acid
      protein. The deduced amino acid sequence contains all of the peptide sequences
      obtained from the proteolytic cleavage of the native enzyme and shares 28%
      sequence identity with a putative Escherichia coli pyridoxal kinase, identified
      for its ability to compliment pyridoxal kinase deficient cells. The T. brucei
      pyridoxal kinase gene was expressed in E. coli and the purified enzyme was found
      to have pyridoxal kinase activity, confirming that this gene encodes the
      functional T. brucei enzyme. Native and recombinant pyridoxal kinase have a
      monomer molecular weight of 37 kDa by SDS-polyacrylamide gel electrophoresis (SDS
      PAGE) and are dimers in solution. Native T. brucei pyridoxal kinase catalyzes the
      phosphorylation of pyridoxal with a specific activity of 990 nmol min(-1) per mg
      and apparent Km values for pyridoxal and ATP of 22 and 9 microM. respectively.
      Substrate inhibition is observed for pyridoxal. Similar results were obtained for
      the recombinant enzyme.

PMID- 9274863
TI  - Structure of the Trypanosoma brucei U6 snRNA gene promoter.
AB  - Transcription in vivo of small nuclear and cytoplasmic RNA genes of Trypanosoma
      brucei was previously shown to require the A and B blocks of a divergently
      transcribed tRNA or tRNA-like gene located approximately 100 nucleotides (nt)
      upstream. To understand the functioning of these transcription units, we have
      used the U6 snRNA/tRNA(Thr) genes as a model system. Saturation mutagenesis
      revealed that for transcription in vivo three elements are essential and
      sufficient. In addition to the previously described A and B boxes, sequences in
      the U6 coding region close to the 5' end participate in positioning RNA
      polymerase III at the start site, and thus constitute a third promoter element.
      We further showed that the function of the upstream A box, but not the B box, is
      strictly dependent upon its distance to the U6 gene internal control region.
      Using our recently developed transcription extract we further demonstrated that
      in vitro U6 transcription requires only the intragenic sequences and the upstream
      A box of the tRNA(Thr) gene. This apparent discrepancy between the in vivo and in
      vitro requirements is highly reminiscent of U6 snRNA gene transcription in the
      yeast Saccharomyces cerevisiae, and suggests the possibility that similar to the
      yeast system the B block of the trypanosome U6 snRNA gene promoter might be
      involved in chromatin organization.

PMID- 9274864
TI  - Temperature acclimation of Trypanosoma cruzi epimastigote and metacyclic
      trypomastigote lipids.
AB  - This study examines the changes in cellular lipids that take place when
      Trypanosoma cruzi epimastigotes and metacyclic trypomastigotes are transferred
      from 28 to 37 degrees C. We found a rise in the sterol to phospholipid ratio, as
      well as in the triacylglycerol and steryl ester cellular content in T. cruzi
      epimastigotes. In addition, saturated to unsaturated fatty acid ratios in
      phospholipids increase. This latter effect appears to be due to two concurrent
      processes. Firstly, fatty acyl delta9 and, especially, delta12 desaturations are
      significantly diminished at 37 degrees C. Secondly, triacylglycerols and steryl
      esters undergo changes in their fatty acyl composition opposite to those
      simultaneously observed in phospholipids, i.e. the ratio of saturated to
      unsaturated fatty acids markedly decreases. Similar alterations in each of the
      lipid classes and in the fatty acid composition of polar and neutral lipids were
      found in cultured metacyclic trypomastigotes on exposure to the same shift-up.
      These observations suggest that a global remodeling of cellular lipids that
      involves extensive fatty acid exchange between neutral and polar lipid pools
      represents a novel and important mechanism of adaptation of the parasites to the
      temperature changes they encounter in their life cycle.

PMID- 9274865
TI  - Polyamine biosynthesis in Cryptosporidium parvum and its implications for
      chemotherapy.
AB  - This study demonstrates that polyamine biosynthesis in Cryptosporidium parvum
      occurs via a pathway chiefly found in plants and some bacteria. The lead enzyme
      of this pathway, arginine decarboxylase (ADC) was sensitive to the specific,
      irreversible inhibitor DL-alpha-difluoromethyl-arginine (IC50 30 microM), and
      intracellular growth of C. parvum was significantly reduced by inhibitors of ADC.
      No activity was detected using ornithine as substrate, and the irreversible
      inhibitor of ornithine decarboxylase, DL-alpha-difluoromethyl-ornithine, had no
      effect upon ADC activity or upon growth of the parasite. Back-conversion of
      spermine to spermidine and putrescine via spermidine:spermine-N1
      acetyltransferase (SSAT) was also detected. Compounds such as
      his(ethyl)norspermine, which have been demonstrated to down-regulate SSAT
      activity in tumor cells, were synergistic in the inhibition of growth when used
      in combination with inhibitors of the forward pathway. Thus, C. parvum differs
      fundamentally in its polyamine metabolism from the majority of eukaryotes,
      including humans. Such differences indicate that polyamine metabolism may serve
      as a chemotherapeutic target in this organism.

PMID- 9274866
TI  - Cloning and characterization of actin depolymerizing factor from Toxoplasma
      gondii.
AB  - We determined the predicted amino acid sequence of actin depolymerizing factor
      (ADF) from Toxoplasma gondii by sequencing the full-length cDNA. T. gondii ADF
      consists of 118 amino acids (calculated molecular weight 13,400) and shares a
      high degree of sequence similarity to other low molecular weight actin monomer
      sequestering proteins, especially Acanthamoeba actophorin, plant ADFs and yeast
      and vertebrate cofilin. ADF from T. gondii is smaller and does not contain a
      nuclear localization sequence like the related vertebrate proteins. Southern blot
      analysis indicates that T. gondii ADF is a single-copy gene. Homogeneous
      recombinant T. gondii ADF purified from E. coli is active in binding actin
      monomers and depolymerizing F-actin. Localization of ADF by immunofluorescence
      and immunoelectron microscopy indicates ADF is scattered throughout the cytoplasm
      and prominently localized beneath the plasma membrane in T. gondii.

PMID- 9274867
TI  - Cathepsin B-like cysteine proteinase-deficient mutants of Leishmania mexicana.
AB  - Mutants null for the cathepsin B-like cysteine proteinase gene (cpc) of
      Leishmania mexicana have been generated by targeted gene disruption. The gene
      deletion was confirmed using a polymerase chain reaction (PCR) method with cpc
      specific primers and genomic DNA isolated from the mutants. cpc was re-expressed
      in the null mutants from an episomal vector. Re-expression of the enzyme (CPC)
      was detected by Western blotting with a specific anti-peptide antiserum. The cpc
      null mutants grew apparently normally as promastigotes and amastigotes in axenic
      cultures, but they showed greatly reduced infectivity to macrophages in vitro
      with only a low percentage of the cells being infected. Re-expression of cpc in
      the null mutant increased the parasite's infectivity in vitro. The null mutant
      parasites formed lesions in mice at a similar rate as wild type parasites,
      although somewhat smaller lesions were produced. The results suggest that
      although the cysteine proteinase encoded by cpc plays a role in the parasite's
      interaction with macrophages it alone is not crucial for infectivity or
      virulence.

PMID- 9274868
TI  - Molecular cloning and characterisation of a putative aspartate proteinase
      associated with a gut membrane protein complex from adult Haemonchus contortus.
AB  - A cDNA was isolated from an adult Haemonchus contortus cDNA expression library
      the deduced amino acid sequence of which showed significant homology to mammalian
      pepsinogen sequences. The library was screened with antisera raised against
      Haemonchus galactose-containing glycoprotein complex, a gut membrane protein
      complex with aspartyl proteinase activity which has shown considerable potential
      as a protective antigen. The amino acid sequence obtained corresponded very
      closely in part to the N-terminal amino acid sequences of two polypetides within
      the complex. The enzyme was shown to be almost exclusively expressed by the blood
      feeding parasite stages. The cDNA was expressed in E. coli, and antibody produced
      to the recombinant protein bound to the luminal surface of the gut in the adult
      parasite. The proteinase may play a central role in digesting the blood meal and
      is considered a potential sub-unit vaccine candidate.

PMID- 9274869
TI  - Stage-specific gene expression in Angiostrongylus cantonensis: characterisation
      and expression of an adult-specific gene.
AB  - We have previously used differential mRNA display to identify and clone a range
      of cDNAs derived from genes expressed in only one developmental stage of
      Angiostrongylus cantonensis. In this paper we report the characterisation of a
      gene designated Ac-fmp-1 and its product, expressed only in the adult stage. Full
      length cDNA of 1.5 kb terminates at the 5' end with the conserved nematode
      spliced leader (SL) sequence and contains one open reading frame coding for a
      putative protein of 417 amino-acids. The recombinant protein expressed from this
      open reading frame is antigenic in the infected host and polyclonal antibodies
      raised against the recombinant protein recognize a 66 kDa protein present only in
      adult female worms. This protein localises to the muscle cell membranes adjacent
      to the pseudocoelom. Nine kb of genomic DNA has been amplified by polymerase
      chain reaction and 7 kb has been cloned and sequenced. This sequence includes 1.5
      kb of 5' flanking region and 5.5 kb of the Ac-fmp-1 gene sequence. In this
      sequence, corresponding to approximately 0.8 kb of the cDNA, the exon/intron
      pattern has been determined.

PMID- 9274870
TI  - A comparison of the enzymatic properties of the major cysteine proteinases from
      Trypanosoma congolense and Trypanosoma cruzi.
AB  - Congopain and cruzipain, the major cysteine proteinases from Trypanosoma
      congolense and Trypanosoma cruzi, were compared for their activities towards a
      series of new, sensitive fluorogenic substrates of the papain family of cysteine
      proteinases and for their sensitivity to inhibition by cystatins and related
      biotinylated peptidyl diazomethanes. Low Ki values, in the 10 pM range, were
      found for the interaction of both proteinases with natural cystatin inhibitors.
      The kinetic constants for the hydrolysis of cystatin-derived substrates, and the
      inhibition by related diazomethanes were essentially identical. Unlike cathepsins
      B and L, the related mammal papain family proteinases, congopain and cruzipain
      accomodate a prolyl residue in P2'. Substrates having the sequence VGGP from P2
      to P2' were hydrolysed by both congopain and cruzipain with a k(cat)/Km greater
      than 4.10(3) mM(-1) s(-1). Irreversible diazomethane inhibitors, deduced from the
      unprime sequence of cystatin-derived substrates, inhibited the two parasite
      proteinases. N-terminal labelling of diazomethanes with a biotin group did not
      alter the rate of inhibition significantly, which provides a useful tool for
      examining the distribution of these enzymes in the parasite and in the host.
      Despite their similar activities on cystatin-derived substrates, congopain and
      cruzipain had significantly different pH-activity profiles when assayed with a
      cystatin-derived substrate. They were correlated with structural differences,
      especially at the presumed S2 subsites.

PMID- 9274871
TI  - Molecular characterization and ultrastructural localization of Plasmodium
      falciparum Hsp 60.
AB  - Heat shock proteins (Hsp) are a group of highly conserved proteins which are
      widely represented phylogenetically. Genes for members of the Hsp 70, 90 and 60
      families have been cloned from the human malaria parasite Plasmodium falciparum.
      In this study, we have cloned and expressed the P. falciparum Hsp 60 (PfHsp60) in
      E. coli. The sequence analysis identified a previously unknown intron of 257 bp
      beginning after the nucleotide 142 in the coding sequence. Antisera raised
      against the recombinant PfHsp60 was employed in immunoprecipitation studies with
      biosynthetically labeled parasite extracts to investigate regulation of
      expression of PfHsp60 at various temperatures. In contrast to the three to four
      fold accumulation of PfHsp60 transcripts in heat shocked parasites (37-40 degrees
      C), the expression of PfHsp60 was not induced in the blood stages of P.
      falciparum. On the other hand, the effect of heat induction on PfHsp70 was seen
      both at the level of specific mRNA and protein. In these studies we also observed
      co-immunoprecipitation of a number of other cellular proteins suggesting possible
      interaction with PfHsp60. Immunofluorescence analysis indicated the presence of
      PfHsp60 in the cytoplasm of all the various stages of the parasite. In addition,
      immunoelectron microscopic analysis distinctly localized PfHsp60 in the
      mitochondrion of P. falciparum. This study suggests that different mechanisms are
      involved in the regulation of expression of various members of the heat shock
      proteins in the parasite.

PMID- 9274873
TI  - Stage-specific expression of a selectable marker in Toxoplasma gondii permits
      selective inhibition of either tachyzoites or bradyzoites.
AB  - The establishment of culture conditions suitable for inducing differentiation of
      Toxoplasma gondii tachyzoites into parasites resembling the latent bradyzoite
      form has opened this important developmental transition to experimental analysis.
      In order to develop a genetic marker suitable for positive and negative selection
      during parasite differentiation. the T. gondii HXGPRT gene was placed under
      control of 5' flanking sequences derived from two bradyzoite-specific genes: BAG1
      and LDH2. Random transgene integration at undefined genomic loci resulted in
      modest regulation (approximately 5-6-fold induction) above relatively high
      background levels (approximately 4% of wild-type controls). Integration of
      transgenes at a defined genomic position was achieved by targeting the uracil
      phosphoribosyl transferase (UPRT) locus using flanking homologous sequences and
      fluorouracil selection. This strategy was found to provide the added advantage of
      enhancing bradyzoite induction frequencies under conditions of pyrimidine
      starvation (low CO2). Constructs integrated in the direction of normal UPRT
      transcription exhibited moderate levels of inducibility, but transgenes
      integrated in the opposite direction were dramatically induced under
      differentiation conditions: 50-100-fold above the very low levels observed in
      tachyzoites (< 1% control). Positive selection (using mycophenolic acid) was
      shown to inhibit tachyzoites but not bradyzoites, while negative selection (using
      8-azahypoxanthine) inhibited bradyzoites only. Stage-specific regulation of the
      HXGPRT selectable marker should permit genetic selections for the identification
      of mutants in the bradyzoite differentiation process.

PMID- 9274872
TI  - A cytidine deaminase expressed in the post-infective L3 stage of the filarial
      nematode, Brugia pahangi, has a novel RNA-binding activity.
AB  - A number of genes have been identified that are highly expressed in the post
      infective L3 stage of the filarial parasite, Brugia pahangi. Amongst these was a
      cDNA with homology to the cytidine deaminase (CDD) gene family. Phylogenetic
      analysis of the various cytosine nucleoside deaminases suggest that Brugia
      pahangi CDD evolved with significant divergence from the RNA editing family. In
      order to characterize its function, we have expressed Brugia pahangi CDD in
      bacteria as a chimera with maltose-binding protein (MBP). Biochemical analysis
      demonstrates the MBP-CDD fusion protein functions as an authentic cytidine
      deaminase with an obligate requirement for zinc. In addition to cytidine
      deaminase activity, however, the fusion protein demonstrates RNA binding activity
      with specificity for AU-rich sequences and was found to bind an RNA template
      spanning the edited site of mammalian apolipoprotein B (apoB) mRNA. This RNA
      binding activity was not found in two different recombinant bacterial CDD
      proteins. In vitro RNA editing assays revealed that MBP-CDD failed to mediate
      cytidine deamination of a mammalian apoB RNA template. Furthermore, binding of
      MBP-CDD to the apoB RNA did not inhibit in vitro editing of this template by
      apobec-1. The data suggest that the cytosine nucleoside deaminases and RNA
      editing deaminases have acquired different mechanisms of binding to an AU-rich
      RNA template, presumably with different functional implications.

PMID- 9274874
TI  - Isolation of a substance from the mosquito that activates Plasmodium
      fertilization.
AB  - We have isolated a small, heat stabile, hydrophilic molecule from the gut lumen
      of unfed, female Anopheles stephensi that is a potent inducer of gametogenesis in
      Plasmodium falciparum and P. gallinaceum at a hydrogen ion concentration, pH 7.4,
      that normally suppresses activation. This gamete activation factor (GAF) was
      purified using reverse phase high performance liquid chromatography and
      determined to have a major ion m/z of 206.1 by low resolution electrospray mass
      spectrometry. The molecule, which was also found in the heads of both female and
      male A. stephensi, absorbed light in the ultraviolet region at three maxima
      (lambda(max) = 213, 245 and 350 nm); the 245/350 nm absorbance ratio was 7.0. The
      structure of the molecule and its normal function in the mosquito are not yet
      known, but in a sample of diverse insect species, extracts from those that feed
      on blood were bioactive. We propose that GAF is the previously observed malaria
      exflagellation factor (MEF).

PMID- 9274875
TI  - Molecular cloning of the gene encoding the 83 kDa amastigote surface protein and
      its identification as a member of the Trypanosoma cruzi sialidase superfamily.
AB  - Amastigote surface proteins of Trypanosoma cruzi are likely targets of both
      humoral and cell-mediated immune responses, however, few such molecules have been
      well studied. In this study, we have used modified RACE (rapid amplification of
      cDNA ends) and SOE (gene splicing by overlap extension) polymerase chain reaction
      strategies to clone the gene for the previously described 83 kDa amastigote
      surface protein of T. cruzi. Of the several clones obtained, only one clone,
      clone 4, was found to encode the 20 amino acid sequence originally reported by
      Pan and McMahon-Pratt (J Immunol 1989;143:1001-1008). The identity of the cloned
      gene with the 83 kDa amastigote surface protein was further confirmed by the
      reactivity of polyclonal antisera against the purified 83 kDa protein with the
      gene product expressed in E. coli. Sequence analyses revealed that this
      amastigote surface protein (ASP-2) has two conserved aspartic acid box motifs and
      the highly conserved VTVxNVxLYNR motif characteristic of bacterial and viral
      sialidases and the type III module of fibronectin, respectively. ASP-2 thus joins
      ASP-1 as a member of the amastigote surface expressed family of sialidase-like
      molecules having strong homology with family 2 of the sialidase/trans-sialidase
      gene superfamily of T. cruzi.

PMID- 9274876
TI  - A Plasmodium falciparum homologue of the ATPase subunit of a multi-protein
      complex involved in chromatin remodelling for transcription.
AB  - A Plasmodium falciparum homologue of one of the components of a chromatin
      remodelling complex which controls binding of transcription factors to nucleosome
      core particles has been cloned and characterised. The gene encodes 1422 amino
      acids with an estimated molecular mass of 167 kDa. The protein, SNF2L, shares 60%
      amino acid identity in its conserved DNA-dependent ATPase domain with yeast
      transcription factors originally identified by characterising mating type switch
      mutants. It also contains sequences related to the so-called SWI3, ADA2, N-CoR
      and TFIIIB B" or SANT DNA binding domains which are characteristic of these
      transcriptional activation factors. The SNF2L gene has two short introns in the
      3' region of the coding sequence of the gene and is transcribed into a single
      approximately 6.5 kb messenger RNA species which is present throughout the
      asexual stages of the cell cycle. Southern blotting and pulsed field gel
      electrophoresis experiments show that SNF2L is a single copy gene. located on P.
      falciparum chromosome 11.

PMID- 9274877
TI  - Isolation of a cDNA encoding Fasciola hepatica cathepsin L2 and functional
      expression in Saccharomyces cerevisiae.
AB  - Cathepsin L2 is a major cysteine proteinase secreted by adult Fasciola hepatica.
      The enzyme differs from other reported cathepsin Ls in that it can cleave peptide
      substrates that contain proline in the P2 position. A cDNA was isolated from an
      expression library by immunoscreening with antiserum prepared against purified
      native cathepsin L2. This cDNA was sequenced and shown to encode a complete
      preprocathepsin L proteinase. Functionally active recombinant cathepsin L
      proteinase was expressed and secreted by Saccharomyces cerevisiae transformed
      with the cDNA. The recombinant enzyme was purified from large-scale fermentation
      broths using ultrafiltration and gel filtration chromatography on Sephacryl S200
      HR columns. NH2-terminal amino acid sequencing showed that the cleavage point for
      activation of the recombinant pro-enzyme is identical to that of the F. hepatica
      produced cathepsin L2. The mature active recombinant proteinase behaved similarly
      to the native enzyme when analysed by SDS-PAGE, immunoblotting and zymography and
      also cleaved peptides containing proline in the P2 position. Finally, the
      recombinant cathepsin L2 cleaved fibrinogen to form a fibrin clot, a property we
      described for F. hepatica cathepsin L2.

PMID- 9274878
TI  - The incorporation, modification and turnover of fatty acids in adult Schistosoma
      mansoni.
AB  - Schistosoma mansoni is known to be unable to synthesize fatty acids and sterols
      de novo, but the parasite is capable of synthesizing phospholipids and
      triacylglycerols from precursors obtained from the host. The present study
      focuses on the dynamics of the incorporation of fatty acids in adult parasites.
      This study showed that fatty acids were rapidly metabolized into complex lipids
      and that oleate (18:1) was efficiently converted to eicosenoate (20:1) by chain
      elongation, whereas palmitate was not elongated at an appreciable rate. This
      chain elongation mainly involved fatty acids that were previously esterified to
      complex lipids. Furthermore it was shown that in adult parasites triacylglycerols
      do not serve as fatty-acyl donors in phospholipid synthesis as had been suggested
      to be the case in schistosomula, because: (1) Immediately after pulse-labelling
      the specific activity of fatty acids in phospholipids was higher than in
      triacylglycerols; and (2) the specific activity of eicosenoate, which had been
      formed by chain elongation of incorporated oleate. was higher in phospholipids
      than in triacylglycerols. Fatty acids that were esterified to phospholipids had a
      high turnover, in contrast to fatty acids esterified to triacylglycerols, which
      persisted for extended periods of time in this lipid class (days rather than
      hours).

PMID- 9274879
TI  - Localization and functional analysis of the cytosolic and extracellular CuZn
      superoxide dismutases in the human parasitic nematode Onchocerca volvulus.
AB  - This study describes the histological localization of two CuZn superoxide
      dismutases (SOD1 and SOD2) in the parasitic nematode Onchocerca volvulus, and a
      functional characterization of the 'extracellular' form of this enzyme (SOD2)
      which provides evidence that it is involved in the defense against environmental
      superoxide anion radicals. These essential enzymes are detected in larval and
      adult stages of the parasite, determined at the mRNA and protein levels by in
      situ hybridization and immunolocalization studies. These proteins are distributed
      throughout the worm, at various concentrations with particularly high levels
      produced in the hypodermis. In vitro maintenance of parasites indicated that SOD2
      was secreted outside the parasite into the medium. Baculovirus constructs
      designed to test the ability of the SOD2 hydrophobic N-terminal region to
      function in processing and secretion confirmed the ability of this polypeptide
      sequence to direct the secretion of a marker protein, as well as of the mature
      SOD2 enzyme. Analyses of the native, mature SOD2 enzyme molecular mass, and the
      primary and quaternary structure, indicate that unlike other extracellular SODs,
      the SOD2 is active as a non-glycosylated dimer, rather than as a tetrameric
      glycoprotein. The detection of SOD2 outside of the parasite maintained in vitro,
      and the confirmation that the SOD2 is a secreted enzyme, indicate that this
      enzyme plays a role in the interactive biology of parasitic nematodes with their
      hosts.

PMID- 9274880
TI  - Molecular characterization and expression of two putative protective excretory
      secretory proteins of Haemonchus contortus.
AB  - It has been shown that vaccination with two low molecular mass excretory
      secretory (ES) antigens of 15 and 24 kDa, respectively, afforded a substantial
      degree of protection against Haemonchus contortus to sheep. In vitro cultivation
      of the parasite usually yields a limited amount of these proteins and therefore,
      recombinant DNA technology was employed to clone the cDNAs encoding the ES
      proteins of interest and to express them in a convenient vector system. The N
      terminal amino acid sequences of the two ES products were determined. Specific 5'
      primers were used in combination with an oligo (dT) 3' primer to amplify the
      appropriate cDNAs by polymerase chain reaction (PCR). A lambda ZAPII cDNA library
      was constructed from mRNA of L5 larvae and subsequently screened with the PCR
      products. The full length clone of the 15 kDa ES protein coded for a 17.2 kDa
      precursor molecule of 148 amino acids with a signal peptide of 30 amino acids.
      The full length clone of the 24 kDa ES protein coded for a 24.6 kDa precursor
      protein of 222 amino acids with a leader sequence of 19 residues. The expression
      of both ES products appeared to be developmentally regulated; mRNA encoding
      occurs only in the parasitic life stages. A cDNA of each ES protein was sub
      cloned, without the leader sequence, into a pQE9 expression vector. Both purified
      recombinant proteins were recognized by sera from H. contortus hyperimmunised
      sheep as judged by immunoblot analysis, suggesting that antigenic determinants
      were also present on the recombinant proteins.

PMID- 9274881
TI  - The antimalarial drug, chloroquine, interacts with lactate dehydrogenase from
      Plasmodium falciparum.
AB  - We have previously shown that a radioiodinated photoreactive analogue of
      chloroquine, [125I]N-(4-(4-diethylamino-1-methylbutylamino)quinolin-6-yl) -4
      azido-2-hydroxybenzamide ([125I]ASA-Q), specifically labels two proteins in
      Plasmodium falciparum with apparent molecular weights (Mr) of 42 and 33 kDa
      (Foley M, Deady LW, Ng K, Cowman AF, Tilley L. J Biol Chem 1994:269:6955-6961).
      We now report the identification of the 33 kDa protein. The 33 kDa protein was
      purified from Plasmodium falciparum using photoaffinity labeling with [125I]ASA-Q
      to monitor the enrichment process. N-terminal sequence analysis of the purified
      protein revealed exact identity of the first 35 amino acids with P. falciparum
      lactate dehydrogenase (PfLDH). The plasmodial enzyme was cloned and expressed in
      E. coli and the recombinant protein used to produce a rabbit antiserum.
      Immunoprecipitation using affinity-purified anti-PfLDH antibodies confirmed the
      identity of the 33 kDa CQ-binding protein. The enzyme activity of purified PfLDH
      was not significantly affected by chloroquine indicating that PfLDH is not a
      direct target of CQ. PfLDH was, however, shown to be exquisitely sensitive to
      inhibition by free heme and chloroquine protected against this inhibitory effect.

PMID- 9274882
TI  - Entamoeba histolytica contains a gene encoding a homologue to the 54 kDa subunit
      of the signal recognition particle.
AB  - We have determined the nucleotide sequence and predicted amino acid sequence of
      the 54 kDa subunit of the signal recognition particle (SRP54) from the
      amitochondrial protist Entamoeba histolytica. The SRP54 gene was isolated from a
      genomic library using a polymerase chain reaction (PCR) probe. Nucleotide
      sequence analysis of a 2.3 kb fragment, derived from a 7 kb genomic clone,
      revealed an open reading frame encoding a protein of 487 amino acids (MW 53.8
      kDa). The identities of the predicted amino acid sequence with its homologues
      from other species were between 24 and 47%. Functional domains previously defined
      for the SRP54-type proteins were present in the entamoebal sequence, such as the
      amino-terminal GTP binding domain (G domain) and the carboxy-terminal methionine
      rich domain (M domain). SRP54 mRNA contains an extra G residue at the 5' end,
      suggesting that capping of poly-A(+) transcripts is present in E. histolytica.
      Evolutionary analysis of the SRP54 based on phylogenetic inference placed the E.
      histolytica sequence as an early divergence of the eukaryotic tree. Although the
      function of the entamoebal homologue remains to be elucidated, the identification
      of the SRP54 gene constitutes the first evidence for SRP related proteins in
      protozoans.

PMID- 9274883
TI  - Characterisation of the gene encoding adenylosuccinate lyase of Plasmodium
      falciparum.

PMID- 9274884
TI  - Analysis of Plasmodium falciparum multidrug-resistance (pfmdr1) gene mutation by
      hairpin-dependent cleavage fragment length polymorphism.

PMID- 9274885
TI  - Periodic synthesis of kinetoplast DNA topoisomerase II during the cell cycle.

PMID- 9274886
TI  - Cloning and characterization of heat shock protein DnaJ homologues from
      Plasmodium falciparum and comparison with ring infected erythrocyte surface
      antigen.

PMID- 9274887
TI  - The gene for histone H2A from the insect trypanosome Crithidia fasciculata.

PMID- 9274888
TI  - Sporozoites of Plasmodium yoelii infect mice with targeted deletions in ICAM-1
      and ICAM-2 or complement components C3 and C4.

PMID- 9274889
TI  - Chondroitin sulfate of thrombomodulin is an adhesion receptor for Plasmodium
      falciparum-infected erythrocytes.

PMID- 9274890
TI  - 1997 ASP Leadership Conference: report on the status of subspecialty training.

PMID- 9274891
TI  - The prevention of early postmenopausal bone loss by cyclical etidronate therapy:
      a 2-year, double-blind, placebo-controlled study.
AB  - PURPOSE: To determine whether intermittent cyclical etidronate therapy can
      prevent early postmenopausal bone loss. PATIENTS AND METHOD: This was a 2-year
      outpatient, randomized, double-blind, placebo-controlled clinical trial. The
      subjects were 152 women within 1 to 10 years of the onset of menopause and bone
      mineral density (BMD) between 0 and -2 SD of normal values for a 50 year old
      woman. The women were stratified according to years since the menopause (1 to 3
      years: n = 43; 4 to 6 years: n = 53; 7 to 10 years: n = 56). Measurements of
      lumbar spine, proximal femur and total body BMD were performed at baseline, 12
      and 24 months by dual x-ray absorptiometry. Biochemical markers of bone
      resorption and bone formation were measured on the same visits. RESULTS: One
      hundred thirty-five subjects completed the study. Mean percentage change in
      lumbar spine BMD (and SEM) at 2 years was +2.14 (0.47)% in the etidronate group
      and -1.72 (0.41)% in the placebo group. Results for lumbar spine BMD in the
      treated and control groups stratified according to years since the menopause
      were: 1 to 3 years: +1.73 (0.84)% and -3.30 (0.70)%; 4 to 6 years: +1.37 (0.88)%
      and -1.80 (0.61)%; 7 to 10 years: +3.42 (0.61)% and -0.38 (0.70)%. The effect of
      both treatment group and menopausal stratum were highly statistically significant
      for lumbar spine and total body BMD. Treatment group, but not stratum, was
      significant for BMD in the proximal femur. Markers of bone resorption and bone
      formation were significantly decreased by etidronate therapy. CONCLUSIONS:
      Cyclical etidronate prevents bone loss in the total skeleton and at the
      clinically relevant sites (spine and proximal femur) even in the early
      postmenopausal years. Hence, it appears to be an effective and safe nonhormonal
      therapy in postmenopausal women with normal or low BMD.

PMID- 9274892
TI  - Acute abdomen in systemic lupus erythematosus: the importance of early
      laparotomy.
AB  - BACKGROUND: Acute abdomen (AA) in systemic lupus erythematosus (SLE) is a
      challenging diagnostic and therapeutic problem. Most patients are on steroid
      and/or immunosuppressive treatment and mortality is high. METHODS: We assessed
      the relationship between the causes of AA in SLE and the SLE disease activity
      index (SLEDAI). RESULTS: Of 51 patients with SLE and AA, 36 had active disease
      (Group 1) and 15 inactive disease (Group 2). Group 1 included 19 patients with
      vasculitis (mean SLEDAI 15.4, range 13 to 24). Three patients with intraabdominal
      thrombosis and high titers of anticardiolipin antibodies (mean SLEDAI 18.3) and
      14 patients with non-SLE-related AA (SLEDAI 8.2, range 5 to 11). Group 2
      consisted of 15 inactive SLE patients (mean SLEDAI 1.7, range 0 to 4). Mortality
      was high in the active group (14 patients) compared with inactive SLE (2 cases).
      A delay in surgical exploration (39.3 vs 178.6 hours) had a negative influence on
      the prognosis. CONCLUSIONS: In SLE patients with AA, a SLEDAI score below 5 is
      indicative of non-SLE-related AA. Elevated aCL were found in patients with
      intraabdominal thrombosis. AA in inactive SLE is non-SLE-related and has low
      mortality, provided an appropriate surgical treatment is given. Early laparotomy
      influences positively the prognosis of SLE patients with AA.

PMID- 9274893
TI  - The independent role of cytomegalovirus as a risk factor for invasive fungal
      disease in orthotopic liver transplant recipients. Boston Center for Liver
      Transplantation CMVIG-Study Group. Cytogam, MedImmune, Inc. Gaithersburg,
      Maryland.
AB  - PURPOSE: To assess impact of cytomegalovirus (CMV) donor-recipient serostatus,
      infection, or disease on development of invasive fungal infection in orthotopic
      liver transplant recipients. PATIENTS AND METHODS: An analysis of prospectively
      collected data in 146 liver transplant recipients (intention to treat cohort)
      from 4 tertiary care, university-affiliated transplant centers in Boston (Boston
      Center for Liver Transplantation). Patients were observed for 1 year after
      transplantation for the development of CMV infection, CMV disease, CMV pneumonia,
      as well as for the development of opportunistic fungal infections, graft
      survival, and mortality. Weekly cultures were taken of urine and throat and every
      other week of buffy coat for CMV for 2 months, then monthly for 6 months, at 1
      year, and at the time of any clinical illness. Pre- and posttransplant variables
      including CMV-serostatus of donor and recipient, fungal isolation from sterile
      body sites, fungemia, bacteremia, antibiotic use, immunosuppression, treatment
      for rejection, and volumes of blood products were measured. RESULTS: Survival
      analysis demonstrated that 36% of patients with CMV disease developed invasive
      fungal disease within the first year post-transplant compared with 8% of those
      without CMV disease (P < 0.0001). One-year mortality in patients with invasive
      fungal disease was 15 of 22 (68%) compared with 23 of 124 (19%) in those without
      invasive fungal disease (P < 0.001). A multivariable, time-dependent analysis
      demonstrated that being a CMV-seronegative recipient of a CMV-seropositive donor
      organ (P < 0.001), having bacteremia (P = 0.001), UNOS (United Network for Organ
      Sharing) status 4 (need for life support measures) at transplant (P = 0.002), and
      volume of platelets (P = 0.002) were independently associated with invasive
      fungal disease. Restriction of cases of invasive fungal disease to those that
      occurred more than 2 weeks after transplant demonstrated an association with CMV
      disease (P = 0.003), bacteremia (P = 0.003), need for life support (P = 0.03),
      and volume of blood products transfused (P = 0.02). CONCLUSION: CMV disease or
      being a CMV-seronegative recipient of a CMV-seropositive donor organ is an
      important predictor for invasive fungal disease following orthotopic liver
      transplantation.

PMID- 9274894
TI  - Thrombocytopenia in the sepsis syndrome: role of hemophagocytosis and macrophage
      colony-stimulating factor.
AB  - BACKGROUND: Thrombocytopenia is frequently encountered in critically ill patients
      with the sepsis syndrome, but its mechanisms frequently remain undetermined.
      Hemophagocytosis has been reported as a cause of thrombocytopenia in various
      diseases. This prospective study was designed to assess: (1) the incidence of
      hemophagocytosis in patients suffering from both the sepsis syndrome and
      unexplained thrombocytopenia, and (2) the circulating level of the macrophage
      colony-stimulating factor (M-CSF) according to the presence or absence of
      hemophagocytosis. METHODS: Fifty consecutive patients diagnosed with both the
      sepsis syndrome and thrombocytopenia of undetermined origin were studied.
      Hemophagocytosis was diagnosed based on microscopical examination of sternal bone
      marrow aspiration by two independent observers. Serum M-CSF concentrations were
      measured in each patient and compared with levels of a normal population (n =
      59). Causes and severity of sepsis syndromes as well as serum M-CSF levels were
      compared between patients with and without hemophagocytosis. RESULTS:
      Hemophagocytosis was diagnosed in 32 patients (64%). Mean serum M-CSF levels were
      increased in patients when compared with normal subjects (539 +/- 141 versus 208
      +/- 82 IU/mL: P < 0.001), and higher in patients with than without
      hemophagocytosis (580 +/- 145 versus 457 +/- 89 IU/mL: P = 0.01). Multiorgan
      dysfunction and infection were independent risk factors of hemophagocytosis (odds
      ratio = 31.3 and 6.8, 95% confidence interval (CI) = 5.4 to 177.6 and 1.0 to
      47.4, P <0.0001 and P = 0.03, respectively). CONCLUSIONS: Hemophagocytosis is a
      frequent cause of unexplained thrombocytopenia in patients with severe sepsis
      syndrome. Our results suggest that M-CSF is overproduced in the sepsis syndrome,
      particularly when hemophagocytosis is present. The role of M-CSF in the
      initiation and development of hemophagocytosis remains to be determined.

PMID- 9274895
TI  - Cigarette smoking and severe uncontrolled hypertension in inner-city African
      Americans.
AB  - PURPOSE: Although over the past 2 decades great strides have been made in
      increasing the awareness, detection, and treatment of hypertension (HTN), actual
      control of blood pressure is far from optimal. We hypothesized that current
      cigarette smoking, by acting as a marker for poor health related behavioral
      patterns, would be significantly associated with uncontrolled blood pressure
      (BP). PATIENTS AND METHODS: Over a 3-month period in 1994, all patients who
      presented to a public hospital medical walk-in clinic were screened, and had
      their BP measured if they had been prescribed BP medication within 1 year and
      were aware of their diagnosis of HTN. Patients were defined as controlled
      hypertensives if both systolic BP and diastolic BP were < or = 140/90 mm Hg.
      Severe uncontrolled hypertensives were those with either systolic BP > or = 180
      mm Hg or diastolic BP was > or = 110 mm Hg. RESULTS: Of the 221 patients meeting
      all inclusion criteria (1 refusal), 86 had uncontrolled HTN (mean BP = 192/106 mm
      Hg), 130 were controlled (mean BP = 130/80 mm Hg), and 5 were not African
      American. Severe uncontrolled hypertensives, when compared with controlled
      hypertensives, were significantly more likely to be current (versus former)
      smokers (odds ratio [OR] = 4.17; 95% confidence interval [CI]: 1.8 to 9.5), and
      be less compliant with medications (OR = 2.33; 95% CI: 1.3 to 4.1). Age, gender,
      alcohol use, marital status, education, and comorbidity were not associated with
      HTN control. In an adjusted logistic regression model, both current and never
      smokers when compared with former smokers were significantly more likely to have
      uncontrolled HTN in compliant patients (OR = 14.4; 95% CI: 3.3 to 63.3 and OR =
      5.7; 95% CI: 1.5 to 21.7, respectively). In noncompliant patients, smoking status
      was not associated with uncontrolled HTN. CONCLUSION: In disadvantaged African
      American patients who report good medication compliance, former smoking status is
      strongly associated with HTN control. Physicians may need to be especially
      vigilant of BP control in patients who smoke.

PMID- 9274897
TI  - Hypercalcemia of malignancy.

PMID- 9274896
TI  - Hypovolemia in syncope and orthostatic intolerance role of the renin-angiotensin
      system.
AB  - PURPOSE: Orthostatic intolerance is the cause of significant disability in
      otherwise normal patients. Orthostatic tachycardia is usually the dominant
      hemodynamic abnormality, but symptoms may include dizziness, visual changes,
      discomfort in the head or neck, poor concentration, fatigue, palpitations,
      tremulousness, anxiety and, in some cases, syncope. It is the most common
      disorder of blood pressure regulation after essential hypertension. There is a
      predilection for younger rather than older adults and for women more than men.
      Its cause is unknown; partial sympathetic denervation or hypovolemia has been
      proposed. METHODS AND MATERIALS: We tested the hypothesis that reduced plasma
      renin activity, perhaps from defects in sympathetic innervation of the kidney,
      could underlie a hypovolemia, giving rise to these clinical symptoms. Sixteen
      patients (14 female, 2 male) ranging in age from 16 to 44 years were studied.
      Patients were enrolled in the study if they had orthostatic intolerance, together
      with a raised upright plasma norepinephrine (> or = 600 pg/mL). Patients
      underwent a battery of autonomic tests and biochemical determinations. RESULTS:
      There was a strong positive correlation between the blood volume and plasma renin
      activity (r = 0.84, P = 0.001). The tachycardic response to upright posture
      correlated with the severity of the hypovolemia. There was also a correlation
      between the plasma renin activity measured in these patients and their
      concomitant plasma aldosterone level. CONCLUSIONS: Hypovolemia occurs commonly in
      orthostatic intolerance. It is accompanied by an inappropriately low level of
      plasma renin activity. The degree of abnormality of blood volume correlates
      closely with the degree of abnormality in plasma renin activity. Taken together,
      these observations suggest that reduced plasma renin activity may be an important
      pathophysiologic component of the syndrome of orthostatic intolerance.

PMID- 9274898
TI  - Resource utilization control processes as indicators of quality in managed care
      organizations: a proposal.
AB  - Central to the development of a competitive market for managed care products is
      the ability to measure the quality of care provided by individual managed care
      organizations (MCOs). Several types of quality measures could be considered for
      this purpose: patient and provider satisfaction, a listing of specific services
      provided to patients, or clinical outcomes of such services. Although assessing
      quality with measures of the process of care is commonplace, we propose
      developing measures of the production processes that control utilization of
      health care resources within an organization. Evaluation of these production or
      resource utilization control processes, although not a substitute for health
      outcomes assessment, may improve our knowledge of the delivery of services within
      managed care organizations. We present a paradigm for evaluation of health care
      resource utilization control processes within managed care organizations based on
      our description of internal and external controls for health care resource
      management. This paradigm can serve as a framework for further research into the
      quality of care provided by these organizations and the processes of health care
      resource management in MCOs.

PMID- 9274899
TI  - Insulin resistance implications for type II diabetes mellitus and coronary heart
      disease.
AB  - PURPOSE: To review information on the implications of insulin resistance for type
      II diabetes mellitus (non-insulin-dependent diabetes mellitus) and coronary heart
      disease, and to derive guidance from this information for the management of these
      conditions. DATA SOURCES: A MEDLINE search of English-language articles published
      between 1985 and July 1996, and review of the bibliographies of articles obtained
      through the MEDLINE search and textbooks. STUDY SELECTION: Primary research
      articles, reviews and perspectives on the epidemiology of diabetes and
      cardiovascular diseases and on intervention outcomes in these diseases. DATA
      EXTRACTION: Study design and quality were assessed, with particular attention to
      methods, study population size and other characteristics. Conclusions of review
      articles and perspectives were analyzed critically. DATA SYNTHESIS: Type II
      diabetes is associated with a two- to fourfold excess of coronary heart disease,
      compared to nondiabetic populations. In most studies, glycemia and duration of
      clinical diabetes were found to be only weak risk factors for coronary heart
      disease. Conventional coronary heart disease risk factors such as dyslipidemia
      and hypertension have been associated with coronary heart disease in type II
      diabetes subjects. Hyperinsulinemia and insulin resistance have been predictive
      of the development of type II diabetes and, in some studies, of coronary heart
      disease. CONCLUSION: Strategies to prevent the development of coronary heart
      disease in diabetic and possibly prediabetic subjects should emphasize a
      multifactorial approach, including: a) improved glycemic control; b) aggressive
      treatment of risk factors for coronary heart disease, including insulin
      resistance; c) primary prevention of NIDDM; and d) use of glucose lowering agents
      that improve insulin sensitivity and cardiovascular risk factors.

PMID- 9274900
TI  - Porphyria cutanea tarda in a dialyzed patient with hepatitis C virus infection:
      dramatic efficacy of small repeated phlebotomies.

PMID- 9274901
TI  - Lymphadenitis associated with the administration of clindamycin.

PMID- 9274903
TI  - Evaluating an ethics consultation service.

PMID- 9274904
TI  - Improving ambulatory management of asthmatic patients.

PMID- 9274905
TI  - Ursodeoxycholic acid in the treatment of AIDS-associated cholangiopathy.

PMID- 9274906
TI  - Diabetes, tissue infarction, and calciphylaxis.

PMID- 9274907
TI  - N-(4-hydroxyphenyl)retinamide activation of a distinct pathway signaling
      apoptosis.

PMID- 9274908
TI  - Gene therapy: mastering the basics, defining details.

PMID- 9274909
TI  - Environmental "endocrine disrupters" get a global look.

PMID- 9274910
TI  - How endogenous estrogens work.

PMID- 9274911
TI  - Cancer review panel recommends a major overhaul of prevention research.

PMID- 9274912
TI  - Oncologists judge themselves the best judges of cancer treatments.

PMID- 9274913
TI  - Involvement of reactive oxygen species in N-(4-hydroxyphenyl)retinamide-induced
      apoptosis in cervical carcinoma cells.
AB  - BACKGROUND: The inhibitory effects of N-(4-hydroxyphenyl)retinamide (4HPR) on
      tumorigenesis and tumor growth may result from its ability to induce apoptosis
      (programmed cell death). Since antioxidants inhibit 4HPR-induced apoptosis,
      experiments were planned to determine whether the levels of reactive oxygen
      species increase in cells undergoing apoptosis after exposure to 4HPR. METHODS:
      Cells of the human cervical carcinoma cell line C33A and normal human cervical
      epithelial cells were treated with 4HPR and analyzed for survival, induction of
      apoptosis, generation of reactive oxygen species, and expression of the apoptosis
      related proteins Bcl-2 and Bax. RESULTS: Treatment with 4HPR decreased C33A cell
      number by inducing apoptosis in a time- and dose-dependent fashion. DNA
      fragmentation typical of apoptosis was observed in cells exposed to 4HPR at
      concentrations of 3 microM or higher for 6-24 hours. The generation of reactive
      oxygen species was enhanced by 1.85-fold to 4.5-fold after a 1.5-hour treatment
      with 0.4-10 microM 4HPR. Pyrrolidine dithiocarbamate, an oxygen radical
      scavenger, suppressed the rate of generation of reactive oxygen species and
      inhibited 4HPR-induced apoptosis. 4HPR failed to modulate cellular levels of the
      Bcl-2 and Bax proteins. N-(4-Methoxyphenyl)retinamide, the major 4HPR metabolite,
      and several other retinoids that bind to nuclear retinoic acid receptors or
      retinoid X receptors failed to enhance the generation of reactive oxygen species
      and to induce apoptosis. 4HPR was much less effective in generating reactive
      oxygen species and in inducing apoptosis in normal human cervical epithelial
      cells than in C33A cervical carcinoma cells. CONCLUSIONS: Enhancement of the
      generation of reactive oxygen species may be involved in apoptotic pathway
      induction by 4HPR.

PMID- 9274914
TI  - Synergistic induction of HL60 cell differentiation by ketoconazole and 1-desoxy
      analogues of vitamin D3.
AB  - BACKGROUND: The goal of differentiation therapy is to induce cancer cells to stop
      proliferating and to express characteristics of normal cells. Vitamin D
      analogues, such as the deltanoids, are being evaluated as differentiation agents
      in the treatment of several human cancers (e.g., myeloid leukemias); however,
      these compounds have a tendency to produce hypercalcemia in patients receiving
      therapy. A combination of a differentiation-inducing deltanoid with a compound
      that blocks entry of calcium into cells (e.g., ketoconazole) may offer a new
      approach to differentiation therapy and address the problem of hypercalcemia. We
      investigated whether various ketoconazole-deltanoid combinations would alter
      cellular differentiation or intracellular calcium homeostasis in comparison with
      deltanoids used alone. METHODS: Cultured human leukemia HL60 cells were treated
      with ketoconazole-deltanoid combinations. Markers of differentiation (expression
      of CD11b and CD14 antigens and of non-specific esterase) were measured by flow
      cytometry and cytochemistry; cell cycle distribution was measured by flow
      cytometry of propidium iodide-stained cells. Expression of differentiation
      related genes was assessed by northern blotting and immunoblotting, and changes
      in intracellular calcium homeostasis were monitored by fluorescence analysis of
      fura-2-containing cells. RESULTS: Ketoconazole strongly potentiated the
      differentiating activity of the deltanoids, which exhibited low potency when used
      alone. Ketoconazole-deltanoid combinations had little effect on HL60 cell-cycle
      distribution, although the cells did stop proliferating and they differentiated.
      Ketoconazole-deltanoid combinations produced only minor changes in intracellular
      calcium homeostasis compared with changes produced by 1,25-dihydroxyvitamin D3,
      either alone or in combination with ketoconazole. CONCLUSION: These results
      suggest that ketoconazole may be useful in combination with vitamin D analogues
      in the differentiation therapy for myeloid leukemias.

PMID- 9274915
TI  - CYP2E1 genetic polymorphisms and risk of nasopharyngeal carcinoma in Taiwan.
AB  - BACKGROUND: Nasopharyngeal carcinoma occurs disproportionately among individuals
      of Chinese descent. The cytochrome P450 2E1 enzyme (CYP2E1) is known to activate
      nitrosamines and other carcinogens that are possibly involved in the development
      of this disease. Certain alleles of the CYP2E1 gene are thought to be more highly
      expressed than others, and their distribution varies between Asian and Caucasian
      populations. We conducted a case-control study to investigate whether such
      variations affect the risk of developing nasopharyngeal cancer. METHODS: Three
      hundred sixty-four patients with nasopharyngeal carcinoma (96% of 378 eligible
      patients) and 320 control subjects (86% of 374 eligible subjects) were studied. A
      risk factor questionnaire was administered to participants to assess factors
      postulated to be linked to nasopharyngeal carcinoma. Peripheral blood was
      obtained from all subjects and DNA was purified from nucleated cells. A
      polymerase chain reaction-based restriction fragment length polymorphism assay
      that used the restriction enzymes Rsa I and Dra I was used to detect wild-type
      and variant forms of the CYP2E1 gene. RESULTS: Individuals homozygous for an
      allele of the CYP2E1 gene that is detected by Rsa I digestion (c2 allele) were
      found to have an increased risk of nasopharyngeal carcinoma (relative risk [RR] =
      2.6; 95% confidence interval [CI] = 1.2-5.7); this effect was limited to
      nonsmokers (RR = 9.3; 95% CI = 2.7-32) and was not affected by alcohol
      consumption. CONCLUSIONS: Our findings suggest that the CYP2E1 genotype is a
      determinant of nasopharyngeal carcinoma risk.

PMID- 9274916
TI  - Correlation of vascular endothelial growth factor expression and microvessel
      density in cervical intraepithelial neoplasia.
AB  - BACKGROUND: Angiogenesis (the formation of new blood vessels) appears to be
      required for the growth of invasive tumors, but little information exists about
      its role in the development of preinvasive lesions. We examined microvessel
      density and expression of vascular endothelial growth factor in specimens of
      cervical intraepithelial neoplasia (CIN), a preinvasive lesion of the uterine
      cervix, to determine whether a connection could be established between these
      parameters of angiogenesis and the grade of dysplasia (i.e., tissue abnormality).
      METHODS: Sections of biopsy specimens from 83 patients with grades I-III CIN were
      examined retrospectively. Microvessels were localized by use of a polyclonal
      antibody directed against factor VIII-related antigen; vascular endothelial
      growth factor was detected by means of a monoclonal antibody. Reported P values
      are two-sided. RESULTS: Highest microvessel densities and highest expression of
      vascular endothelial growth factor were found in a narrow border region between
      CIN lesions and the underlying stroma. A significant correlation was observed
      between high vascular endothelial growth factor expression and high microvessel
      density (Kendall's tau = 0.27; 95% confidence interval [CI] = 0.03-0.50; P =
      .018). Mean microvessel density values +/- standard deviations for CIN I, CIN II,
      and CIN III lesions were 19.4 +/- 5.8, 21.9 +/- 7.0, and 34.1 +/- 14.8,
      respectively (Kendall's tau = 0.46; 95% CI = 0.30-0.61; P<.0001). Corresponding
      values for vascular endothelial growth factor expression were 8.3 +/- 3.5, 8.4 +/
      2.0, and 12.2 +/- 3.6, respectively (Kendall's tau = 0.41; 95% CI = 0.20-0.60;
      P<.0001). CONCLUSIONS: Our results are consistent with the idea that progression
      of cervical dysplasia is dependent on angiogenesis.

PMID- 9274917
TI  - Doxorubicin disaccharide analogue: apoptosis-related improvement of efficacy in
      vivo.
AB  - BACKGROUND: Although doxorubicin remains one of the most effective agents for the
      treatment of solid tumors, there is an intensive effort to synthesize doxorubicin
      analogues (compounds with similar chemical structures) that may have improved
      antitumor properties. We have synthesized a novel doxorubicin disaccharide
      analogue (MEN 10755) and have characterized some of its relevant biochemical,
      biologic, and pharmacologic properties. METHODS: The antitumor activity of this
      compound (MEN 10755) was studied in a panel of human tumor xenografts, including
      xenografts of A2780 ovarian tumor cells, MX-1 breast carcinoma cells, and POVD
      small-cell lung cancer cells. MEN 10755 was compared with doxorubicin according
      to the optimal dose and schedule for each drug. The drug's cytotoxic effects,
      induction of DNA damage, and intracellular accumulation were studied in A2780
      cells. DNA cleavage mediated by the enzyme topoisomerase II was investigated in
      vitro by incubating fragments of simian virus 40 DNA with the purified enzyme at
      various drug concentrations and analyzing the DNA cleavage-intensity patterns.
      Drug-induced apoptosis (programmed cell death) in tumors was determined with the
      use of MX-1 and POVD tumor-bearing athymic Swiss nude mice. RESULTS: MEN 10755
      was more effective than doxorubicin as a topoisomerase II poison and stimulated
      DNA fragmentation at lower intracellular concentrations. In addition, MEN 10755
      exhibited striking antitumor activity in the treatment of human tumor xenografts,
      including those of the doxorubicin-resistant breast carcinoma cell line MX-1.
      CONCLUSIONS: The high antitumor activity of MEN 10755 in human tumor xenografts,
      including doxorubicin-resistant xenografts, and its unique pharmacologic and
      biologic properties make this disaccharide analogue a promising candidate for
      clinical evaluation.

PMID- 9274918
TI  - Independent prognostic value of the 67-kd laminin receptor in human prostate
      cancer.

PMID- 9274919
TI  - Association between human papillomavirus type 18 variants and histopathology of
      cervical cancer.

PMID- 9274920
TI  - Diabetes mellitus and risk of large bowel cancer.

PMID- 9274921
TI  - Severe tissue necrosis after cisplatin extravasation at low concentration:
      possible "immediate recall phenomenon".

PMID- 9274922
TI  - The role of delta-opioid receptors in the discriminative stimulus properties of a
      low dose of methamphetamine.
AB  - The effects of selective mu-, delta- and kappa-opioid receptor agonists and
      antagonists on the discriminative stimulus properties of methamphetamine were
      examined in rats that had been trained to discriminate between methamphetamine
      (0.4 mg/kg) and saline. Methamphetamine produced a dose-related increase in
      methamphetamine-appropriate responses in all of the rats. In generalization
      tests, neither morphine (a mu-opioid receptor agonist: 0.3-10 mg/kg) nor 3,4
      dichloro-N-[2-(1-pyrrolidinyl)cyclohexo]benzeneacetamide (U50,488H: a kappa
      opioid receptor agonist: 1.0-8.0 mg/kg) generalized to the discriminative
      stimulus properties of methamphetamine. A newly synthesized non-peptide selective
      delta-opioid receptor agonist 2-methyl-4aalpha-(3-hydroxyphenyl)
      1,2,3,4,4a,5,12,12aalpha- octahydroquinolino(2,3,3,-g)isoquinoline (TAN-67: 32
      mg/kg) partially generalized (70% methamphetamine-appropriate responses) to the
      discriminative stimulus properties of methamphetamine. In combination tests,
      pretreatment with the mu- and kappa-opioid receptor antagonists, beta
      funaltrexamine (9.0 mg/kg) and nor-binaltorphimine (10 mg/kg), respectively, had
      little or no influence on the discriminative stimulus properties of
      methamphetamine. In contrast, pretreatment with naltrindole (a non-selective
      delta-opioid receptor antagonist: 3.0 mg/kg) or naltriben (a selective delta2
      opioid receptor antagonist: 1.0 mg/kg), but not with 7-benzylidenenaltrexone (a
      selective delta1-opioid receptor antagonist: 0.5 and 1.0 mg/kg), significantly
      attenuated the discriminative stimulus properties of methamphetamine. However,
      naltrindole (3.0 mg/kg) did not significantly attenuate the discriminative
      stimulus properties of methamphetamine at a higher training dose (1.0 mg/kg). Our
      findings may have some bearing on the relative importance of the role of delta
      opioid (especially delta2-opioid) receptors in the discriminative stimulus
      properties of a low dose of methamphetamine.

PMID- 9274923
TI  - 8-cyclopentyltheophylline, an adenosine A1 receptor antagonist, inhibits the
      reversal of long-term potentiation in hippocampal CA1 neurons.
AB  - The effects of an adenosine A1 receptor antagonist, 8-cyclopentyltheophylline (8
      CPT, 1 microM), on the reduction of long-term potentiation were studied in CA1
      neurons of guinea pig hippocampal slices. Reduction of long-term potentiation
      (depotentiation) was achieved by delivering a train of low-frequency afferent
      stimuli (low-frequency stimulation, 1000 pulses, 1 Hz) 20 min after the tetanus
      (100 Hz, 100 pulses). In control experiments, low-frequency stimulation reduced
      the potentiated component of the slope of the field EPSP and the amplitude of the
      population spike by 68.5 +/- 14.4% and 80.1 +/- 8.8%, respectively (n = 6); these
      values were significantly reduced to 13.4 +/- 9.7% and 9.0 +/- 10.9% (n = 7) when
      the low-frequency stimulation was applied during the perfusion with 8-CPT (1
      microM). These results indicate that activation of adenosine A1 receptors
      enhances the depotentiation of long-term potentiation.

PMID- 9274925
TI  - Priming of 6-hydroxydopamine-lesioned rats with L-DOPA or quinpirole results in
      an increase in dopamine D1 receptor-dependent cyclic AMP production in striatal
      tissue.
AB  - Priming with a dopamine agonist greatly enhances the behavioral effectiveness of
      dopamine D1 receptor agonists in rats with 6-hydroxydopamine lesions of the
      nigrostriatal pathway. The present study investigated the influence of priming on
      cyclic AMP production in striatal slices. Stimulation of dopamine D1 receptors
      with dopamine or the dopamine D1 receptor agonist, 1-phenyl-6-Cl-7,8-diol-2,3,4,5
      tetrahydro-(1H)-3-benzazepine (SKF 81297), increased cyclic AMP production in the
      lesioned striatum of rats primed with L-3,4-dihydroxyphenylalanine (L-DOPA) by
      329% and 405%, respectively, whereas in drug-naive rats the increase was 183% and
      187%, respectively. Priming with quinpirole produced similar results. It is
      suggested that priming with either L-DOPA or a dopamine D2 receptor agonist
      results in increased effectiveness of dopamine D1 signal transduction, apparently
      not only related to previous stimulation of D1 receptors.

PMID- 9274924
TI  - Supraspinal administration of opioids with selectivity for mu-, delta- and kappa
      opioid receptors produces analgesia in amphibians.
AB  - Previous results using an amphibian model showed that systemic and spinal
      administration of opioids selective for mu, delta and kappa-opioid receptors
      produce analgesia. It is not known whether non-mammalian vertebrates also contain
      supraspinal sites mediating opioid analgesia. Thus, opioid agonists selective for
      mu (morphine; fentanyl), delta (DADLE, [D-Ala2, D-Leu5]-enkephalin; DPDPE, [D
      Pen2, D-Pen5]-enkephalin) and kappa (U50488, trans-3,4-dichloro-N-methyl-N-[2-(1
      pyrrolidinyl)-cyclohexyl] benzeneacetamide methanesulfonate; CI977, (5R)
      (544alpha,744alpha,845beta)-N-methyl-N-[7-(1-p yrr olidinyl)-1-oxaspiro[4,5]dec
      8yl]-4-benzofuranaceta  mide++ + monohydrochloride) opioid receptors were tested
      for analgesia following i.c.v. administration in the Northern grass frog, Rana
      pipiens. Morphine, administered at 0.3, 1, 3 and 10 nmol/frog, produced a dose
      dependent and long-lasting analgesic effect. Concurrent naltrexone (10 nmol)
      significantly blocked analgesia produced by i.c.v. morphine (10 nmol). ED50
      values for the six opioids ranged from 2.0 for morphine to 63.9 nmol for U50488.
      The rank order of analgesic potency was morphine > DADLE > DPDPE > CI977 >
      fentanyl > U50488. These results show that supraspinal sites mediate opioid
      analgesia in amphibians and suggest that mechanisms of supraspinal opioid
      analgesia may be common to all vertebrates.

PMID- 9274926
TI  - Imidapril inhibits increased transforming growth factor-beta1 expression in
      remnant kidney model.
AB  - To elucidate the effect of imidapril, an angiotensin-converting enzyme inhibitor,
      on molecular events in progressive glomerulosclerosis, we administered imidapril
      to 5/6 nephrectomized rats and measured the glomerular expression of genes for
      transforming growth factor (TGF)-beta1, fibronectin and collagen IV. Glomerular
      TGF-beta1, fibronectin and collagen IV mRNAs in nephrectomized rats were
      significantly higher than those in sham-operated rats. Treatment with imidapril
      for 10 weeks significantly reduced the enhanced glomerular expression of TGF
      beta1 and collagen IV mRNA in nephrectomized rats, and prevented the associated
      proteinuria and glomerulosclerosis. Thus, imidapril may arrest progressive
      glomerulosclerosis by inhibiting the expression of TGF-beta1 and collagen IV.

PMID- 9274927
TI  - Characterization of des-Arg9-bradykinin-induced contraction in guinea-pig
      gallbladder in vitro.
AB  - We have reported that bradykinin induces graded contraction in guinea-pig
      gallbladder in vitro through activation of bradykinin B2 receptors and prostanoid
      release, while des-Arg9-bradykinin, a selective bradykinin B1 receptor agonist,
      causes only a weak contraction, suggesting the presence of badykinin B1 receptors
      in this tissue. In the present study, we attempted to characterise the receptor
      subtype and the possible mechanism by which des-Arg9-bradykinin induces
      contraction in this preparation. Contractions induced by des-Arg9-bradykinin in
      guinea-pig gallbladder (1 pM to 1 microM) increased significantly as a function
      of time elapsed after setting up of the preparation, reaching the maximum after 6
      h of equilibration (EC50 16.4 pM and Emax 0.6 +/- 0.08 g). Des-Arg9-bradykinin
      induced contraction in guinea-pig gallbladder was totally prevented by
      cycloheximide (70 microM, an inhibitor of protein synthesis), indomethacin (3
      microM), ibuprofen (30 microM), phenidone (30 microM) or Ca2+-free medium plus
      EGTA, and was partially antagonised by MK 571 ((3-(3-(2-(7-chloro-2-quinolinyl)
      ethenyl) phenyl ((3-dimethyl amino-3-oxo-propyl) thio) methyl) propanoic acid,
      0.1 microM) or by nicardipine (1 microM), but was not affected by dazoxiben (30
      microM), staurosporine (100 nM) or L 655,240 (240 (3-[1-(4-clorobenzil)-5-fluoro
      3-metilhyindol-2il] 2,2-dimetilpropanoic acid, 1 microM). Unexpectedly, des-Arg9
      bradykinin-induced contraction was unaffected by the selective bradykinin B1
      receptor antagonists, des-Arg9-[Leu8]-bradykinin and des-Arg9-NPC 17761 (des-Arg0
      D-Arg [Hip3, D-HipE (transtiofenil)7, Oic8]-des-Arg9-bradykinin). However, the
      selective bradykinin B2 receptor antagonists, HOE 140 (D-Arg0-[Hyp3, Thi5, D
      Tic7, Oic8]-bradykinin) and NPC 17731 (D-Arg0 [Hyp3, DHypE (transpropyl)7, Oic8]
      bradykinin), completely blocked des-Arg9-bradykinin-mediated contraction. Pre
      treatment of the animals with Escherichia coli endotoxin (lipopolysaccharide, 30
      microg/animal, i.v., 24 h) did not significantly change the response to des-Arg9
      bradykinin induction. It is concluded that des-Arg9-bradykinin-induced
      contractions in guinea-pig gallbladder are mediated primarily by the release of
      proinflammatory eicosanoid(s) derived from the cyclo-oxygenase pathway. These
      effects are unrelated to thromboxane A2 and do not seem to be coupled to
      activation of a protein kinase C-dependent mechanism. Response to des-Arg9
      bradykinin increases as a function of the equilibration period of the preparation
      by a mechanism dependent on protein synthesis and seems to be mediated by
      activation of bradykinin B2 (but not B1) receptors. Finally, in contrast to that
      observed for bradykinin, the contraction induced by des-Arg9-bradykinin in guinea
      pig gallbladder is fully dependent on the influx of extracellular Ca2+, partially
      through L-type Ca2+ channels.

PMID- 9274928
TI  - KMD-3213, a novel alpha1A-adrenoceptor antagonist, potently inhibits the
      functional alpha1-adrenoceptor in human prostate.
AB  - KMD-3213, (-)-(R)-1-(3-hydroxypropyl)-5-[2-[[2-[2-(2,2,2-trifluoroethoxy)phe
      noxy]ethyl]amino]propyl]indoline-7-carboxamide, is a novel and selective alpha1A
      adrenoceptor antagonist. The potency of this drug to antagonize functional alpha1
      adrenoceptor-mediated contraction in human prostatic smooth muscle was evaluated
      and compared with that of other alpha1-adrenoceptor antagonists. KMD-3213
      inhibited noradrenaline-induced contractions with an apparent pK(B) value of 9.45
      +/- 0.039, indicating a potency similar to that of tamsulosin. The affinity of
      prazosin for prostatic alpha1-adrenoceptors is given as potency for the alpha1L
      adrenoceptor with an estimated pA2 value of 8.84 +/- 0.044. The data obtained in
      this study suggest that KMD-3213, an alpha1A-adrenoceptor-selective antagonist,
      has strong affinity for the alpha1L-adrenoceptor in the human prostate.

PMID- 9274930
TI  - Anxiolytic homophthalazines increase Fos-like immunoreactivity in selected brain
      areas of the rat.
AB  - Nerisopam, an anxiolytic and antipsychotic homophthalazine induces rapid, intense
      expression of Fos-like immunoreactivity in the rostral, dorsomedial and lateral
      parts of the striatum in the rat. Fos-positive cells also occurred in the globus
      pallidus, the olfactory tubercle and in the accumbens nucleus (in the cone and
      shell portions) but the substantia nigra, the entopeduncular and the subthalamic
      nuclei were virtually Fos-negative. 5 h after nerisopam application, however,
      cells in the reticular zone of the substantia nigra showed Fos-like
      immunopositivity. After a daily application of nerisopam for two weeks,
      relatively weak Fos-like immunoreactivity was observed in the striatum and the
      subthalamic nucleus but not in the globus pallidus. Unilateral surgical
      transection of the striato-nigral pathway, which depleted tyrosine hydroxylase
      immunostaining in the ipsilateral striatum did not influence nerisopam-induced
      Fos-like immunoreactivity in the striatal neurons, either ipsi- or contralateral
      to the knife cut. Our results suggest that the striatal neurons are the primary
      targets of this anxiolytic and antipsychotic drug in the central nervous system.

PMID- 9274929
TI  - Pro-inflammatory effects induced by bradykinin in a murine model of pleurisy.
AB  - Bradykinin caused a dose-related increase in cell influx 4 h after its
      administration into the mouse pleural cavity (ED50 = 3.2 nmol/cav., 95%
      confidence limits = 0.6-15.5). Cell influx peaked at 4 h and remained elevated
      for up to 72 h, whereas exudation was detected between 2 and 6 h after bradykinin
      administration. Both HOE 140 (D-Arg-[Hyp3,Thi5,D-Tic7, Oic8]bradykinin) and NPC
      17731 (D-Arg0-[Hyp3 D-HypE(transpropyl7)Oic8]bradykinin) inhibited bradykinin
      induced cell influx (ID50 0.028 (0.05-0.16) and 0.4 (0.3-0.7) pmol/cav.,
      respectively). Des-Arg9-[Leu8]bradykinin (0.1 and 3.0 nmol/cav., 30 min before)
      did not inhibit the effects of bradykinin. Pre-treatment of animals with either
      indomethacin, terfenadine, dexamethasone, N(omega)-nitro-L-arginine benzyl ester,
      cromolyn, theophylline, salbutamol, FK 888 (N2-[(4R)-4-hydroxy-1-(1-methyl-1H
      indol-3-yl)carbonyl-L-propyl]N-met hyl-N-phenyl-methyl-3-(2-naphthyl)-L
      alaninamide) or SR 142801 ((N)-(1-[3-[1-benzoyl-3-(3,4-dichloro-phenyl)-piperidin
      3-yl]pr opy l]-4-phenyl-piperidin-4-yl)-N-methyl-acetamide) significantly
      inhibited cell migration (P < 0.01). These results indicate that bradykinin had a
      significant pro-inflammatory effect on the pleural cavity of the mice. This
      effect seems to be primarily mediated via activation bradykinin B2 receptors
      which trigger the release of other mediators.

PMID- 9274931
TI  - Dexamethasone inhibits cytokine-induced intercellular adhesion molecule-1 up
      regulation on endothelial cell lines.
AB  - Intercellular adhesion molecule-1 (ICAM-1) expression on three endothelial cell
      lines was differently modulated by pro-inflammatory cytokines, such as
      interleukin-1beta and tumour necrosis factor-alpha (TNF-alpha) and the
      glucocorticoid hormone dexamethasone. Incubation of EA.hy926 cells with 1 microM
      dexamethasone prior to addition of TNF-alpha consistently reduced ICAM-1
      induction by approximately 40%. EA.hy926 cell responsiveness to the steroid was
      validated by detecting specific dexamethasone binding, with a calculated affinity
      constant of 1.3 nM and a maximal number of sites of 35 x 10(3) per cell. To
      establish the generality of dexamethasone inhibition upon ICAM-1 up-regulation,
      two other endothelial cell lines were assessed. Incubation of LT4 and ECV304
      cells with interleukin-1beta or TNF-alpha produced a significant increase in ICAM
      1 expression on their cell surface (ranging from a 2-fold increase for
      interleukin-1beta to a 5-fold increase for TNF-alpha). Addition of dexamethasone
      was again able to significantly reduced this induction. Finally, the effect of
      the steroid on cytokine-induced ICAM-1 up-regulation was functionally related to
      its ability to suppress in vitro neutrophil trans-endothelial passage. Overall
      these data indicate that ICAM-1 is a likely molecular target for the anti
      inflammatory action exerted by dexamethasone. Inhibition of ICAM-1 up-regulation
      may, at least in part, mediate the potent anti-migratory action displayed by this
      class of anti-inflammatory drugs.

PMID- 9274932
TI  - Cell type-specific regulation of beta2-adrenoceptor mRNA by agonists.
AB  - Prolonged agonist stimulation of beta2-adrenoceptors results in receptor down
      regulation which is often paralleled by a reduction of the corresponding mRNA. In
      this study, we investigated the agonist-dependent regulation of beta2
      adrenoceptor mRNA in DDT1-MF2 smooth muscle cells and C6 glioma cells. In DDT1
      MF2 cells the half-life of the mRNA was 12 h in monolayer compared to 2 h in
      suspension cultures. Under both conditions, the agonist isoproterenol reduced
      this half-life by a factor of 2. In contrast, in C6 glioma cells isoproterenol
      had no effect on the mRNA stability, even though it reduced mRNA levels by
      approximately 50%. Isoproterenol-induced downregulation of beta2-adrenoceptor
      mRNA was completely blocked in C6 cells by the presence of a protein synthesis
      inhibitor, while this was not so in DDT1-MF2-cells. These data show that beta2
      adrenoceptor downregulation occurs via cell-type specific mechanisms.

PMID- 9274933
TI  - Stimulus dependence of non-steroidal antiinflammatory drug potency in a cellular
      assay of prostaglandin H synthase-2.
AB  - The prostaglandin H synthase-2 selective non-steroidal antiinflammatory drugs
      nimesulide, NS-398 (N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide),
      flosulide and SC 58125 (5-(4-fluorophenyl)-1-[4-(methylsulfonyl)phenyl]-3
      (trifluoromethyl)-1H- pyrazole) as well as the non-selective non-steroidal
      antiinflammatory drugs indomethacin, meclofenamate and ibuprofen were compared in
      a WISH (human amnionic epithelial cell) cellular assay of prostaglandin H
      synthase-2 activity. Varying amounts of prostaglandin E2 were induced in WISH
      cells using either interleukin-1beta, tumor necrosis factor-alpha or phorbol 12
      myristate 13-acetate, alone or in combination, or with okadaic acid as
      stimulants. The results from these studies demonstrated that under conditions
      which generate greater amounts of prostaglandin E2, the potency of both
      prostaglandin H synthase-2 selective and non-selective non-steroidal
      antiinflammatory drugs may be reduced. Dexamethasone, a transcriptional inhibitor
      of prostaglandin H synthase-2, also became progressively less effective in cells
      activated by combinations of stimuli or with okadaic acid. We conclude that
      decreases in potency under conditions of high levels of prostaglandin H synthase
      2 expression and prostaglandin E2 production are observed equally with
      prostaglandin H synthase-2 selective and non-selective inhibitors.

PMID- 9274934
TI  - Interrelation between nitric oxide synthase and heme oxygenase in rat endothelial
      cells.
AB  - The gene expression and interrelation of the constitutive type nitric oxide (NO)
      synthase-III as a NO-forming enzyme and heme oxygenase-2 as a carbon monoxide
      forming enzyme were studied in cultured rat aortic endothelial cells. Both NO
      synthase-III and heme oxygenase-2 mRNAs were demonstrated in the endothelial
      cells by RNAase protection analysis. NO synthase-III mRNA was upregulated in the
      presence of the heme oxygenase inhibitor, zinc protoporphyrin IX, but not in the
      presence of the NO synthase inhibitor, N(G)-nitro-L-arginine. Although heme
      oxygenase-2 mRNA was significantly upregulated in the presence of both NO
      synthase inhibitor and heme oxygenase inhibitor, the increase was greater with
      the NO synthase inhibitor. These results provide the first evidence for the
      concomitant gene expression of NO synthase-III and heme oxygenase-2, and their
      compensatory interrelation in endothelial cells.

PMID- 9274935
TI  - GYKI 53665, a 2,3-benzodiazepine, non-competitively protects cultured neurones
      against AMPA toxicity.
AB  - The nature of the neuroprotection by the competitive alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, 6-nitro-7-sulfamoyl
      benzo[f]quinoxaline-2,3-dione (NBQX), and the non-competitive AMPA receptor
      antagonist, 1-(4-aminophenyl)-3-methylcarbamoyl-4-methyl-3,4-dihydro-7,8-methy
      lenedioxy-5H-2,3-benzodiazepine (GYKI 53655), was investigated in mature
      telencephalic neurone cultures of the rat. NBQX protected cultured neurones
      against AMPA-induced delayed toxicity in a competitive manner: the AMPA
      concentration-response curve was shifted to the right in parallel and
      concentration dependently. In contrast, GYKI 53655 decreased the maximal
      neurotoxic effect of AMPA considerably but without affecting the EC50, for AMPA
      toxicity, which indicated the non-competitive mode of its action. Thus we found a
      clear relationship between the nature of in vitro neuroprotection and the mode of
      AMPA channel block.

PMID- 9274936
TI  - Repeated administration of 3,4-methylenedioxymethamphetamine augments cocaine's
      action on dopamine in the nucleus accumbens: a microdialysis study.
AB  - In this study, we examined the ability of a single injection of cocaine (20
      mg/kg, i.p.) to augment extracellular dopamine levels in the nucleus accumbens
      two weeks after pretreating rats with either saline (1 ml/kg, i.p.) or the
      serotonin neurotoxin 3,4-methylenedioxymethamphetamine (20 mg/kg, s.c., twice
      daily for 4 days). The level of dopamine in the nucleus accumbens was measured
      using in vivo microdialysis. Cocaine produced a 400% increase in extracellular
      nucleus accumbens dopamine levels in control rats, whereas in 3,4
      methylenedioxymethamphetamine treated rats the increase produced by cocaine was
      800%, which was significantly different from controls. This suggests that 3,4
      methylenedioxymethamphetamine, a relatively common drug of abuse, may alter
      subsequent vulnerability to cocaine dependence and abuse.

PMID- 9274937
TI  - Enhanced kappa-opioid receptor-mediated analgesia by antisense targeting the
      sigma1 receptor.
AB  - In the current study, we used an antisense oligodeoxynucleotide targeting the
      recently cloned sigma1 receptor to assess its functions within the nervous
      system. Sigma1 antagonists potentiate the analgesic actions of opioids.
      Similarly, the antisense probe targeting the sigma1 receptor enhanced the
      analgesic activity of the kappa1-opioid receptor agonist U50,488H (trans-3,4
      dichloro-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeacetamidel++  +) and the kappa3
      opioid receptor agonist naloxone benzoylhydrazone. A mismatch control was
      inactive. These results confirm the role of sigma1 receptors in an anti-opioid
      analgesic system and illustrate the utility of antisense approaches towards the
      elucidation of sigma receptor functions.

PMID- 9274938
TI  - DNA recommendations. Further report of the DNA Commission of the ISFH regarding
      the use of short tandem repeat systems. International Society for Forensic
      Haemogenetics.

PMID- 9274939
TI  - Allele frequencies of nine STR systems in the Flemish population and application
      in parentage testing.
AB  - In order to apply a set of nine STR loci in parentage testing, we performed a
      population genetic study on a sample of the Flemish population. Genotypes for
      HUMHPRTB, HUMFABP, HUMCD4, HUMCSF1PO, HUMTH01, HUMPLA2A, HUMPLA2A1, HUMF13A01,
      HUMCYAR04 and HUMLIPOL were determined using three triplex PCR reactions and
      silver staining. Allele frequencies showed no deviation from Hardy-Weinberg
      equilibrium. The frequency distribution agreed well with other Caucasian
      populations but three intermediate fragments, not previously found in Caucasians,
      were observed. We then resolved a series of 151 parentage disputes of which 103
      were exclusions. In six cases, evidence for exclusion was obtained by only one
      informative STR locus out of eight for male children or out of nine for female
      children. These exclusions were confirmed with additional polymorphic markers. In
      one case of inclusion, a paternal allele expanded with one repeat unit of
      HUMHPRTB. This observation illustrates that STRs do not differ from other genetic
      systems in the fact that more than one excluding locus is required before
      exclusion is demonstrated.

PMID- 9274940
TI  - DNA typing of epithelial cells after strangulation.
AB  - DNA typing was carried out on epithelial cells which were transferred from the
      hands of the suspect onto the neck of the victim. In an experimental study 16
      suspect-victim combinations were investigated for estimating the typing success.
      Alternatively to an attack against the neck, the upper arm was used for
      "strangulation". PCR typing was carried out using the short tandem repeat systems
      (STRs) HumCD4, HumVWF31A (VWA) and Hum-FIBRA (FGA) and the success rate was > 70%
      for all 3 systems. In most of the cases mixed patterns containing the phenotype
      of the suspect and the victim were obtained. In a case where strangulation was
      the cause of death, epithelial cells could be removed from the neck of the
      victim. The DNA pattern of the suspect could be successfully amplified using four
      STRs, demonstrating the applicability of this approach for practical casework.

PMID- 9274941
TI  - Semi-automatic DNA profiling in a Hungarian Romany population using the STR loci
      HumVWFA31, HumTH01, HumTPOX, and HumCSF1PO.
AB  - A population study of Hungarian Romanies was carried out for the STR loci
      HumVWFA31, HumTH01, HumTPOX, and HumCSF1PO. After multiplex PCR amplification
      semi-automatic DNA profiling was performed using an ALF DNA sequencer. At the
      loci investigated there was little and no evidence for departures from Hardy
      Weinberg expectations and linkage equilibrium, respectively. The allele sizing
      accuracy of the ALF DNA sequencer was increased to a high level (99.97% on
      average) by applying external and internal markers. Allele frequency
      distributions of the STR loci, with one exception, were significantly different
      between the Romany and other Hungarian population databases. On the other hand,
      however, only small differences in frequencies of individual phenotypes were
      found.

PMID- 9274942
TI  - Multiple gunshot suicides: potential for physical activity and medico-legal
      aspects.
AB  - Out of 138 clearly defined gunshot suicides which were autopsied, 11 persons (8%)
      fired two or more gunshots to the body. From these 11, 5 cases involved 2
      gunshots to the head where the bullets fired first had missed the brain. The
      trajectories were restricted to the chest in three cases and a combination of
      gunshots to the head and chest including two perforating heart wounds without
      immediate incapacitation occurred in three more cases. Reliable incapacitation is
      based on physiological effects (tissue disruption) and can only be achieved by
      decreasing the functioning capability of the CNS. This can be accomplished by
      direct disruption of brain tissue or indirectly by cerebral hypoxemia from
      massive bleeding. Targets of immediate incapacitation are restricted to certain
      CNS areas and targets of rapid incapacitation include the heart, the (thoracic)
      aorta and the pulmonary artery. Other major blood vessels and major organs
      (lungs, kidneys, liver, spleen) constitute targets of delayed incapacitation.
      This general classification can be derived from the literature and is illustrated
      by the cases presented. A thorough post mortem can exclude or quantify the
      potential for physical activity. Typical features of single gunshot suicides such
      as contact shots, classical entrance wound sites and soot/backspatter on a hand
      also occur in multiple gunshot suicides.

PMID- 9274943
TI  - Myocardial necrosis and cocaine. A quantitative morphologic study in 26 cocaine
      associated deaths.
AB  - A quantification of different forms of acute myocardial necrosis, myocardial
      leukocytic infiltrates and myocardial fibrosis was accomplished in 26 chronic
      cocaine abusers who died of cocaine intoxication and compared to 45 normal
      subjects who died from head trauma and 38 who died of acquired immunodeficiency
      syndrome. The findings were: absence of infarct necrosis, a similar frequency and
      extent of coagulative myocytolysis (contraction band necrosis) and leukocytic
      infiltrates in cocaine abusers and normal controls, and an absence of myocardial
      fibrosis in cocaine abusers. These findings question both the acute and chronic
      cardiotoxicity of cocaine. The infarct-like pattern in some predisposed subjects
      may be due to an excess of catecholamine release induced by the drug resulting in
      coagulative myocytolysis and platelet thrombi.

PMID- 9274944
TI  - Morphology, immunohistochemistry and morphometry of pancreatic islets in cases of
      sudden infant death syndrome (SIDS).
AB  - The pancreatic islets from 112 infants (66 males and 46 females) who died of SIDS
      during the years 1990-1992 have been studied. The control group consisted of
      endocrine pancreas tissue from 19 infants who died of a clear cause of death
      (pneumonia, drowning, sepsis, etc.). The mean age of the SIDS group was 5.1
      months. We found histologically normally developed organs in all the SIDS cases.
      By evaluating the relative endocrine cell area of the pancreas by
      immunohistochemical investigations, A-cells were found to make up 10-30%, B-cells
      30-60%, D-cells 10-30% and pancreatic polypeptide cells less than 10% in the SIDS
      group and in the controls with a small increase in glucagon and insulin cells
      among SIDS cases. The morphometric evaluation revealed that cell enlargement and
      cytoplasm shrinking occurred slightly more often in the SIDS group than in the
      control group. The diameter of the islets was normal and the maximal volume was
      not enlarged. The results did not show significant differences so that a
      relationship between alterations of the endocrine pancreas and sudden infant
      death syndrome could not be demonstrated.

PMID- 9274945
TI  - Retrospective study on skin reddenings and petechiae in the eyelids and the
      conjunctivae in forensic physical examinations.
AB  - Skin reddening with or without additional changes such as pinpoint intracutaneous
      hemorrhages and/or minute superficial scratches was observed in 165 out of 739
      physical examinations (reddening with additional changes: n = 81; reddening only:
      n = 84). The most common site where reddening was observed was the neck region
      (reddening with additional changes: n = 30; reddening only: n = 34). In over 85%
      of the cases, the postinfliction interval (Pi) was < or = 1 day, and there were
      12 and 10 cases with 1 < Pi < or = 3 days, respectively. Among these 22 cases,
      there were 5 cases with 2 < Pi < or = 3 days, (reddening with additional changes:
      n = 4; reddening only: n = 1). The maximum Pis were almost 3 days, and 2 days and
      13 h, respectively. These results demonstrate that reddening of the skin with and
      that without additional changes (in particular petechiae) were detectable up to
      approximately 3 and 2 days after the event, respectively. Furthermore, in 17 out
      of 64 cases with reddening in the neck, petechial hemorrhages were seen in the
      eyelids and/or conjunctivae (reddening with additional changes: n = 10; reddening
      only: n = 7). The maximum Pi in which petechial hemorrhages were detectable in
      the eyelids and/or the palpebral conjunctivae was 1 day and 21 h. The present
      study indicates that physical examinations within 2 or 3 days after the event
      seem to be more suitable to find skin reddening and/or petechiae in the eye lids
      and/or the conjunctivae.

PMID- 9274946
TI  - ACTBP2 gene frequency distribution and sequencing of the allelic ladder and
      variants in the Japanese and Chinese populations.
AB  - The human beta-actin related pseudogene H-beta-Ac-psi-2 (ACTBP2) gene frequency
      distributions in the Japanese and Chinese Han populations were investigated and
      compared. Analysis was carried out by applying fluorescently labeled samples and
      a differently labeled sequenced allelic ladder within the same lanes in
      denaturing gels, followed by laser detection and automated analysis using
      Genescan software 672. The discrimination index and the heterozygosity index were
      calculated to be 0.993 and 0.916 in the Japanese population, and 0.993 and 0.944
      in the Chinese Han population, respectively. No deviation from Hardy-Weinberg
      equilibrium was observed in these two populations. The allelic ladder, which
      ranged from 233 bp to 319 bp, was constructed from a combination of 23 regularly
      occurring alleles. The allelic ladder and 12 variants observed in 24 individuals
      in these two populations were sequenced. The variants could be divided into three
      types according to their structural variation characteristics. These variants
      differed from the alleles of the same repeats in the allelic ladder by the
      presence or absence of hexanucleotides in the central repeat regions, base
      deletions in the flanking regions, and base insertions in the repeat units.

PMID- 9274947
TI  - The possible role of remnant-like particles as a risk factor for sudden cardiac
      death.
AB  - Postmortem plasma lipid and lipoprotein levels were analyzed in two groups of
      Japanese subjects who died suddenly and unexpectedly due to cardiac (n = 93) or
      non-cardiac (n = 26) causes. No individuals in either group had a significant
      medical or cardiac history. In this study, we measured plasma total cholesterol,
      triglycerides, VLDL-cholesterol, LDL-cholesterol, HDL-cholesterol, and especially
      triglyceride-rich lipoprotein remnants. Triglyceride and apo E-rich remnant-like
      particles (RLP) were studied as a possible risk factor for sudden cardiac death
      in relation to the progression of coronary atherosclerosis. The receiver
      operating characteristic curve (ROC) analysis showed that RLP-TG was the most
      significant risk factor for sudden cardiac death among the lipids and
      lipoproteins and RLP-C was the best predictor for coronary atherosclerosis. HDL-C
      and LDL-C levels were within normal limits in the majority of the cases and did
      not appear to relate to the sudden cardiac death. Apo E phenotyping was performed
      for the detection of the genetic background in the lipid metabolism. The
      frequency of the Apo E3/3 (wild type) phenotype, which closely relates with the
      remnant metabolism, was significantly reduced in the sudden cardiac death group.
      Our study on the postmortem plasma lipid analysis suggested that RLP-C and RLP-TG
      are the best risk predictor for coronary atherosclerosis and sudden cardiac
      death, respectively.

PMID- 9274948
TI  - The usefulness of thiosulfate as an indicator of hydrogen sulfide poisoning:
      three cases.
AB  - We examined the usefulness of thiosulfate as an indicator of hydrogen sulfide
      poisoning by analysing sulfide and thiosulfate in three cases. In the first (non
      fatal) case sulfide and thiosulfate were not detected in the blood samples from
      any of the four workers involved in the accident. In the urine samples, only
      thiosulfate was detected in three out of the four workers at a concentration of
      0.12-0.43 micromol/ml, which was 4-14 times higher than the level in a healthy
      person. In the second (fatal) case sulfide and thiosulfate were detected in the
      blood sample at concentrations of 0.007 micromol/ml for sulfide, and 0.025
      micromol/ml for thiosulfate. The thiosulfate concentration was at least 8 times
      higher than the level in a healthy person. In the third (fatal) case sulfide and
      thiosulfate were detected in the blood sample at concentrations of 0.95
      micromol/ml for sulfide, and 0.12 micromol/ml for thiosulfate. Based on the above
      results, we concluded that thiosulfate in urine is the only indicator to prove
      hydrogen sulfide poisoning in non-fatal cases, while the analysis of sulfide in
      fatal cases should be accompanied by the measurement of thiosulfate in blood.

PMID- 9274949
TI  - Allele frequency distributions of 13 PCR-based systems in a population from North
      East Spain.
AB  - Population data studies were carried out on a Caucasian population from North
      East Spain (n = 129-292 individuals) for 13 PCR-based polymorphic DNA loci: six
      short tandem repeat loci (HumTH01, HumTPOX, HumCSF1PO, HumF13A01, HumFES/FPS,
      HumvWFA31), the six PM loci (HLA-DQ alpha, LDLR, GYPA, HBGG, D7S8, GC) and one
      variable number tandem repeat locus (D1S80). The genotypes distributions were in
      accordance with Hardy-Weinberg expectations. The combined use of the 13
      polymorphic systems provides a high power of discrimination and power of
      exclusion for use in forensic casework and paternity testing.

PMID- 9274950
TI  - Antibody-mediated clean-up of blood for simultaneous HPLC determination of
      morphine and morphine glucuronides.
AB  - For the interpretation of the concentration of morphine in blood samples of
      heroin consumers information about the concentration of the analgesic active
      morphine metabolite morphine-6-glucuronide is very important. Thus a simple but
      specific clean-up procedure based on immuno-affinity chromatography is presented
      for the extraction of morphine, morphine-3-glucuronide and morphine-6-glucuronide
      from whole blood in cases of fatal heroin overdose. The preparation of the
      immunoabsorber by immobilization of antibodies against morphine-3-BSA and
      morphine-6-KLH with carbonyldiimidazole-activated trisacrylgel is described. The
      separation of the extracts is achieved by HPLC using native fluorescence
      detection. The limits of detection for this method are 10ng for morphine and
      morphine glucuronides/g blood. The results for the concentration of morphine and
      morphine glucuronides in blood from seven cases of heroin overdose are presented.
      By calculating the quotients for the concentrations of morphine-6
      glucuronide/morphine the time elapsed since the last intake of heroin is
      estimated.

PMID- 9274951
TI  - Short tandem repeat polymorphism at the HUMCD4 and HUMF13B loci in a Croatian
      population.
AB  - Population studies were carried out on unrelated individuals of Croatian
      ancestry. Genomic DNA was amplified by the polymerase chain reaction (PCR) at the
      polymorphic microsatellite loci HUMCD4 (n = 105 individuals) and HUMF13B (n = 108
      individuals). After horizontal polyacrylamide gel electrophoresis followed by
      silver staining 6 alleles and 12 genotypes were observed for HUMCD4 and 6 alleles
      and 13 genotypes could be identified for HUMF13B. Data obtained were in
      concordance with the prediction of Hardy-Weinberg equilibrium. The allele
      frequency data were compared with Austrian and Italian population samples and no
      significant deviations between these populations were observed.

PMID- 9274952
TI  - Lewis genotyping by the PCR-RFLP method in a Japanese population and its
      evaluation in forensic analysis.
AB  - Lewis phenotyping of red blood cells has many problems such as the influence of
      many biological conditions, the change during the period from newborn to early
      childhood and mistyping by non-specific anti-Lewis antibodies. Therefore, it
      would be useful to determine the Lewis genotype. Recently a method of Le
      genotyping by PCR-RFLP was established. We determined the frequencies of Lewis
      genotypes in a Japanese population and discuss the applicability to paternity
      tests and other forensic applications. The gene frequencies of Le, le1 and le2 in
      the Japanese population studied were 0.7032, 0.2358 and 0.0610 respectively. Out
      of 12 paternity cases where paternity was excluded by other markers, 3 alleged
      fathers could also be excluded by Lewis genotyping. The genotype from organs of a
      fetus from a 3-month pregnancy was Le/Le. The determination of Lewis genotypes
      could play a useful role as a genetic marker in paternity tests and forensic
      analyses.

PMID- 9274953
TI  - Analysis of the short tandem repeat systems HumVWA and HumF13B in a population
      sample from northern Thailand.
AB  - Two STR systems (HumVWA, HumF13B) were analysed in a northern Thailand population
      sample using PCR and gel electrophoresis. No deviations from Hardy-Weinberg
      equilibrium were observed. A rare VWA allele was detected, sequenced and the
      molecular structure is presented. Interpopulation comparisons revealed that the
      Thai allele frequencies were most similar to data from other Asian populations.

PMID- 9274954
TI  - Antioxidant-related enzymes in myocardial zones and human pericardial fluid in
      relation to the cause of death.

PMID- 9274955
TI  - Immunohistochemical analysis of platelet-derived growth factor and its receptors
      in fibrohistiocytic tumors.
AB  - Platelet-derived growth factor (PDGF) is known to stimulate the proliferation of
      fibroblasts, although the role of PDGF and its receptors in the development of
      fibrohistiocytic tumors has not been clarified. In this study, we investigated
      this role by immunohistochemically staining PDGF and PDGF beta-receptors in
      paraffin-embedded dermatofibroma (DF), dermatofibrosarcoma protuberans (DFSP) and
      malignant fibrous histiocytoma (MFH) tissue. We also immunohistochemically
      investigated the relationship between PDGF beta-receptors and CD34, which is a
      known immunohistochemical marker for DFSP. Immunohistochemical studies using anti
      PDGF-AA or BB antibodies showed that PDGF-AA and BB was found in 20 to 40% of the
      tumor cells in DF, DFSP, and MFH. No definite relationship for each tumor type
      was found. The expression of PDGF beta-receptors in DFSP and that of MFH tissue
      was significantly greater in comparison to DF and scar tissue. The expression of
      CD34 and PDGF beta-receptors in DFSP was observed in identical areas. These
      findings suggest that autocrine or paracrine growth stimulation, through PDGF
      beta-receptors, is related to the tumorous proliferation of fibrohistiocytic
      tumors, and the expression of PDGF beta-receptors might play a role in the
      proliferation of CD34 positive tumor cells.

PMID- 9274956
TI  - Interphase cytogenetic demonstration of chromosome 9 loss in thick melanomas.
AB  - It has been postulated that deletion of genes on chromosome 9 is important in the
      development of malignant melanoma. In this study, we have investigated this
      hypothesis by analysing the numerical complement of chromosomes 9, 17 and X by
      interphase cytogenetics using peri-centromeric repeat probes on paraffin sections
      from 15 thick melanomas. Three cases showed no relative loss or gain of
      chromosomes. Two cases showed gain of chromosome 17, and one case loss of
      chromosome 17 relative to chromosomes 9 and X. Relative chromosome 9 loss was
      identified in 9 cases (60%). Two of these were monosomic for chromosome 9 with a
      normal complement of chromosomes 17 and X and six were tetrasomic for chromosome
      17 with duplication of chromosome X: chromosome 9 was disomic in five of these
      cases and trisomic in one. The final case showed loss of both chromosomes 9 and
      17 relative to X. The chromosome patterns obtained imply that loss of chromosome
      9 frequently takes place before tetraploidisation. This is in keeping with the
      hypothesis that loss of chromosome 9 is not a late event in melanocyte
      transformation. Extension of these studies to thin melanomas, in situ melanomas
      and dysplastic naevi will refine further the point at which these changes occur.

PMID- 9274957
TI  - The pathogenesis of large cell transformation in cutaneous T-cell lymphoma is not
      associated with t(2;5)(p23;q35) chromosomal translocation.
AB  - In 20%-50% of the advanced cutaneous T-cell lymphomas (CTCL), malignant T cells
      undergo large cell transformation (LCT). The malignant T cells of LCT in CTCL can
      share morphologic and immunophenotypic similarities with CD30 (Ki-1)-positive
      anaplastic large cell lymphoma (ALCL), suggesting a common mechanism of
      pathogenesis. The t(2;5) (p23;q35) translocation, resulting in the fusion of the
      nucleophosmin (NPM) gene and the anaplastic lymphoma kinase (ALK) gene, is
      associated with primary CD30+ ALCL. To determine whether acquisition of this
      chromosomal translocation is involved in the pathogenesis of LCT in CTCL, we
      examined 12 tumor samples from 9 CTCL patients, including 8 with LCT-CTCL and one
      with concurrent CTCL and Hodgkin's disease, for the presence of the t(2;5)
      translocation. Numerous CD30+ large cells were present in 4 LCT-CTCL consistent
      with secondary CD30+ ALCL; CD30 was expressed by <10% of the large cells in
      another case and was negative in the other 3 lymphomas. Using primers spanning
      the NPM/ALK fusion junction, PCR amplification following reverse transcription
      (RT) of mRNA failed to show the products of NPM/ALK fusion in all samples tested.
      Thus, the t(2;5) (p23;q35) translocation does not appear to be involved in the
      molecular pathogenesis of LCT in CTCL, including CD30+ cases.

PMID- 9274958
TI  - Keratoacanthoma and squamous cell carcinoma: study of PCNA and Le(Y) expression.
AB  - To determine whether keratoacanthoma (KA) is unique or a variant of squamous cell
      carcinoma (SCC), the expressions of proliferating cell nuclear antigen (PCNA) and
      Le(Y) in 16 KA cases (11 fully developed and 5 involutional types; two of the
      involutional types transformed from the fully developed types) and 11 cases of
      well-differentiated SCC were investigated by immunohistochemistry. The monoclonal
      antibodies used were PC-10 for PCNA and BM-1/JIMRO for Le(Y). Le(Y) is one of the
      Lewis-type antigens, and is thought to be related to apoptosis. In most of the
      cases of fully developed KA, the PCNA expression was linear or band-like and was
      limited to the basal and suprabasal layers, while the Le(Y) expression was seen
      in a diffuse pattern throughout the epidermis, except for the basal layer.
      However, in 5 of these cases, there were some areas in the basal and suprabasal
      layer where PCNA-positive cells were few, while Le(Y) expression was very strong.
      In the involutional Ka cases, the PCNA expression was very weak in the basal and
      suprabasal layers, and the Le(Y) expression was strong throughout the epidermis.
      In the SCC cases, the PCNA and Le(Y) expressions were very strong and diffuse
      throughout the tumor masses except for the lack of PCNA in the horny layer and
      the lack of Le(Y) in the basal layer. These findings indicate that there are some
      differences between KA and SCC in the expression pattern of PCNA and Le(Y), and
      that apoptosis may occur in the Le(Y)-positive areas in the basal and suprabasal
      layers and thus cause the involution of KA.

PMID- 9274959
TI  - The clinical and histomorphological features of pityriasis rubra pilaris. A
      comparative analysis with psoriasis.
AB  - Pityriasis rubra pilaris (PRP) is an idiopathic erythematous scaling eruption
      which can be difficult to distinguish from psoriasis. We explored the clinical
      features, including background medical illnesses and potential triggers in
      patients with PRP, and also its histomorphologic spectrum. Patients with PRP were
      selected by natural language search of dermatopathology databases containing
      250,000 cases accessioned over a 3-year period. A detailed medical history was
      obtained on each patient via office chart review and patient interviews. We
      compared the histologic findings in skin biopsies from patients with PRP to those
      of biopsies matched for site and age from control patients with psoriasis.
      Certain aspects of the clinical presentations encountered in the study group
      patients have not been previously emphasized, including eruptions compatible with
      a vesiculobullous disorder in 4 patients. Several patients had evidence of
      underlying iatrogenic or systemic immune dysregulatory states and certain
      triggers could be isolated such as emotional stress and prior exposure to
      microbial pathogens. Histomorphologic features predictive of PRP included
      follicular plugging, an increased granular cell layer, and acantholysis. While
      seen in a minority of biopsies of PRP, morphologic discriminators supportive of a
      diagnosis of psoriasis included neutrophils in the parakeratotic scale crust, and
      dermal papillae capillary ectasia with vessels lying in direct apposition to the
      epidermis. Other morphologic features were encountered in biopsies of PRP which
      have received little emphasis in the dermatopathology literature, including
      epithelial atrophy, significant dermal inflammation, the presence of eosinophils
      and plasma cells within the inflammatory infiltrates, an abnormal granular cell
      layer, and epidermolytic hyperkeratosis, albeit none were statistically
      signficant predictors of PRP over psoriasis. Nevertheless, their identification
      emphasizes the varied histologic spectrum of PRP. The almost ubiquitous finding
      of acantholysis and the presence of an abnormal granular cell layer in many
      biopsies of PRP suggests that abnormal keratins or defects in the retinol
      signalling pathway may be of pathogenetic importance.

PMID- 9274960
TI  - Herpetic syringitis associated with eccrine squamous syringometaplasia in HIV
      positive patients.
AB  - Herpetic syringitis has been described as a rare manifestation of herpes virus
      infection in patients with an immunodeficiency, usually secondary to human
      immunodeficiency virus (HIV) infection. Eccrine squamous syringometaplasia (ESS)
      is an infrequent alteration of the eccrine duct epithelium reported in
      association with several conditions, including chronic ulcers, inflammatory
      processes, and patients receiving chemotherapy. The association of herpetic
      syringitis with ESS has not been reported before. We identified 3 cases of
      herpetic syringitis associated with ESS in patients with the acquired
      immunodeficiency syndrome. In 2 of 3 cases the signs of herpetic syringitis were
      limited to the metaplastic duct epithelium, but in 1 case there were also
      herpetic alterations without ESS. The histological features of herpetic infection
      in HIV-positive patients may be atypical and lack the typical epidermal
      alterations, observing only an extensive epidermal necrosis. In those cases, the
      alterations of the eccrine ducts may be a diagnostic clue in the diagnosis of
      herpetic infection. ESS of the ductal epithelium is probably secondary to the
      herpetic infection, although it might also stimulate the extension of the
      herpetic infection. Further studies are needed to elucidate the association of
      ESS and herpes virus infection.

PMID- 9274961
TI  - Delayed postburn blisters: an immunohistochemical and ultrastructural study.
AB  - This study was performed in an attempt to further elucidate the pathogenesis of
      delayed postburn blistering. Two cases were studied ultrastructurally and
      immunohistochemically, 1 with blisters on the recipient site of autologous split
      thickness skin grafts and the other on the donor site. Ultrastructurally, the
      basement membrane was on the roof of the blisters in both cases, except for a
      single small blister in the first case where it was on the dermal floor. In the
      blister roofs, the basement membrane showed small or marked segments of
      discontinuity. In the adjacent non-blistered healed skin, the basement membrane
      was usually continuous, and anchoring fibrils were present. Immunoperoxidase
      staining on frozen sections, using antibodies to laminin, laminin 5, collagen IV,
      and collagen VII, showed a mostly continuous linear pattern in the adjacent non
      blistered skin, which often became discontinuous near the blisters and markedly
      discontinuous in the blister roofs. In the blister floors, weakly stained linear
      or granular deposits of some of these components were sometimes also present. The
      results of this study support discontinuity of the basement membrane as the main
      anomaly in delayed postburn blistering. Disturbance in the reassembly or local
      breakdown of the basement membrane components might be the underlying defect.

PMID- 9274962
TI  - The nature of cuticular "ruffles" on slowly plucked anagen hair roots.
AB  - When an anagen hair is slowly plucked, the root's surface near the distal end of
      the keratogenous zone shows rings of 'ruffles' which are cuticular scales rolled
      back towards the root tip in a tight curl. During extraction, the rachet-like
      cuticle of the inner root sheath tears apart the almost differentiated cuticular
      scales on the root's cortex. Further extraction rolls up the cuticle because of
      the friction with the inner root sheath cuticle and because the torn
      intercellular cement reconstitutes so that the ruffle's curl is stabilized by
      cohesion (self-gluing). No evidence was found for pretensioning in the root's
      cuticle as an explanation for the curling.

PMID- 9274963
TI  - Retiform hemangioendothelioma. A new case in a child with diffuse endovascular
      papillary endothelial proliferation.
AB  - We present a new case of retiform hemangioendothelioma (RH), an entity first
      described by Calonje et al. in 1994. The tumor was intradermal and located on the
      toe of an 11-year-old boy. Histologically, in addition to the distinctive
      retiform pattern of proliferating vessels in RH there are intraluminal papillae
      with hyaline cores similar to those seen in malignant endovascular papillary
      angioendothelioma (Dabska's tumor), but usually they are infrequent, focal and
      poorly developed. In our case, these papillary structures were well formed and
      distributed in a diffuse way. They were most conspicuous in superficial areas
      where the blood vessels were dilated. In deep areas, where the pattern of
      neoplastic vessels was retiform, the papillae filled their lumina totally,
      resembling solid cords. Our case shares the clinical and morphologic features of
      both retiform hemangioendothelioma and Dabska's tumor, supporting a relationship
      between these two kinds of neoplasms. The benign behavior of this case, with no
      recurrence or metastases over a 4-year follow-up, corresponds to the low
      malignancy of this kind of vascular neoplasm.

PMID- 9274964
TI  - Leukemic cells within skin lesions of psoriasis in a patient with acute
      myelogenous leukemia.
AB  - We report on an 81-year-old man with acute myelo-monocytic leukemia (FAB M4) and
      a long-standing history of psoriasis. Biopsy of psoriatic plaques revealed the
      coexistence of characteristic histopathologic aspects of psoriasis together with
      an infiltrate of blasts with features of myelo-monocytes, suggestive of a
      specific leukemic infiltrate within plaques of psoriasis. Immunohistologic
      stainings showed positivity of blasts for LN2 (CD74), MT1 (CD43), and lysozyme,
      consistent with a myeloid lineage of these cells. To the best of our knowledge,
      this is the first report on the association of psoriasis with myelogenous
      leukemia. The presence of leukemic cells within psoriatic skin plaques may be
      explained by non-specific recruitment of recirculating malignant cells to the
      skin. Alternatively, as psoriasis is an inflammatory disease involving
      granulocytes among other cell types, it may be hypothesized that leukemic cells
      retain to some extent their capability to respond to physiologic stimuli and
      enter the skin in response to specific chemotactic factors.

PMID- 9274965
TI  - Multiple malignant cylindromas of skin in association with basal cell
      adenocarcinoma with adenoid cystic features of minor salivary gland.
AB  - This unusual case is that of a middle-aged man exhibiting a tumor diathesis
      including a basal cell adenocarcinoma with features of adenoid cystic carcinoma
      arising in minor salivary gland of lip in association with multiple primary
      malignant cylindromas of skin. The labial lesion showed invasive tubules, solid
      epithelial sheets and cribriform structures. It did not exhibit PAS positive
      juxta-tubular basement membrane material. The skin lesions all showed features of
      a highly infiltrative cylindromatous carcinoma with two cell types, peripheral
      palisading and prominent PAS positive juxta-tubular basement membrane material.
      Immunocytochemical studies of the lip lesion and one of the skin lesions showed
      similarities, including positive staining for high and low molecular weight
      keratins and S-100 with negative staining for CEA. The precious descriptions of
      tumor diatheses involving dermal cylindromas and dermal analogue tumors of
      salivary glands and the distinctions with the present study are noted. If benign
      and even malignant cylindromas were described in the literature to be associated
      with basal cell adenocarcinoma of the major salivary glands, our case is unique
      by its association with this rare malignant tumor in a minor salivary gland.

PMID- 9274966
TI  - Demodex mites of human skin express Tn but not T (Thomsen-Friedenreich) antigen
      immunoreactivity.

PMID- 9274967
TI  - Centrally administered oligodeoxynucleotides in rats: occurrence of non-specific
      effects.
AB  - We studied the effects of various intracerebroventricularly administered
      oligodeoxynucleotides on body temperature, locomotor activity, food intake and
      water consumption in rats during a 24 h period with a radio-telemetric system.
      Both complete phosphorothioate oligodeoxynucleotides and end-inverted
      oligodeoxynucleotides dose-dependently elevated body temperature, suppressed food
      and fluid intake and inhibited nighttime activity. Apparently these effects do
      not depend on the nucleotide sequence because antisense and sense arginine
      vasopressin and oxytocin oligodeoxynucleotides, as well as a missense
      oligodeoxynucleotide produced comparable changes in the autonomous and behavioral
      parameters. In control experiments neither contaminants from the chemical
      synthesis nor endotoxins produced such effects, whereas native DNA from salmon
      sperm did. Fever and sickness-like behavior in response to missense
      phosphorothioate oligodeoxynucleotides were accompanied by elevated
      concentrations of circulating corticosterone and by a marked increase in
      interleukin 6 mRNA in brain and spleen, indicating that centrally administered
      oligodeoxynucleotides stimulate the production of pyrogenic inflammatory
      mediators in both central nervous system and peripheral tissues. Our results
      indicate that centrally administered oligodeoxynucleotides produce beside their
      intended sequence-specific effects also transient and sequence-independent
      effects due to their nucleic acid structure.

PMID- 9274968
TI  - ACEA 1021, a glycine site antagonist with minor psychotomimetic and amnestic
      effects in rats.
AB  - Antagonists of the allosteric glycine site of the NMDA receptor complex have been
      suggested to be beneficial in the treatment of neurodegenerative disorders.
      However, unwanted side effects like psychomotor stimulation and amnesia must be
      expected. ACEA 1021 (5-nitro-6,7-dichloro-1,4-dihydroquioxaline-2,3dione) is one
      of the first high-selective glycine site antagonists which passes the blood-brain
      barrier and which has promising anticonvulsive and neuroprotective properties. In
      the present study the effects of ACEA 1021 (5, 7.5, 8, 10, 15 and 20 mg/kg i.p.)
      on sniffing stereotypy, locomotor activity, prepulse inhibition of the acoustic
      startle response, the anti-cataleptic properties and spatial learning were
      tested. Only 7.5 mg/kg ACEA 1021 induced a sniffing stereotypy which was
      antagonized by the partial glycine site agonist D-cycloserine (D-4-amino-3
      isoxazolidinone). ACEA 1021 had neither an effect on motor behavior measured in
      the open field nor on the acoustic startle response in the prepulse inhibition
      paradigm nor on the acquisition of spatial learning in the 8-arm-radial maze.
      Anti-cataleptic properties of ACEA 1021 in dopamine D2 (haloperidol (4'fluoro-4
      (1-(4-hydroxy-4-p-chlorophenyl-piperidino)-butyrophe non)) or D1 (SCH 23390 (7
      chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzaze pin e
      hydrochloride)) receptor antagonist-pretreated rats were only minor. Thus, ACEA
      1021 is a glycine site antagonist with minimal psychotomimetic side effects and
      with no amnesia properties. However, it has only minor anti-parkinsonian effects.

PMID- 9274969
TI  - CP-101,606, a potent neuroprotectant selective for forebrain neurons.
AB  - The neuroprotective activity of (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4
      phenylpiperidino)-1-propanol (CP-101,606), an N-methyl-D-aspartate (NMDA)
      receptor antagonist structurally similar to ((+/-)-(R*,S*)-alpha-(4
      hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-++ +piperidineethanol (ifenprodil),
      was investigated in neurons in primary culture. CP-101,606 potently and
      efficaciously protected hippocampal neurons from glutamate toxicity but was > 900
      fold less effective for cerebellar granule neurons. The neuroprotective activity
      in the hippocampal neurons is mediated through a high affinity binding site
      distinct from the agonist and thienylcyclohexylpiperidine (TCP) binding sites of
      the NMDA receptor. Autoradiography indicates the CP-101,606 binding site is
      localized in forebrain, most notably in hippocampus and the outer layers of
      cortex. The functional selectivity for hippocampal neurons, forebrain
      localization of binding sites, and structural relation to ifenprodil suggest that
      CP-101,606 is an NMDA antagonist highly selective for NR2B subunit containing
      receptors.

PMID- 9274970
TI  - Influence of 7-nitroindazole on the anticonvulsive action of conventional
      antiepileptic drugs.
AB  - 7-Nitroindazole (a selective neuronal nitric oxide (NO) synthase inhibitor) at 25
      and 50 mg/kg, 30 min before the test, did not influence the electroconvulsive
      threshold. However, at 50 mg/kg, it enhanced the anticonvulsive activity of
      phenobarbital against maximal electroshock and did not affect that of
      carbamazepine, diphenylhydantoin and valproate. L-Arginine (500 mg/kg) did not
      modify the protective activity of phenobarbital alone or the 7-nitroindazole
      induced enhancement of its anticonvulsive potency against maximal electroshock. 7
      Nitroindazole did not alter the plasma levels of antiepileptic drugs, so a
      pharmacokinetic interaction, in terms of total and free plasma levels, is not
      probable. 7-Nitroindazole combined with the antiepileptics resulted in motor
      disturbances, except for the combination with phenobarbital. On the other hand,
      the combined treatment of 7-nitroindazole with carbamazepine or phenobarbital
      produced effects superior to those produced by single drugs, as regards long-term
      memory. Our results indicate that the protective activity of carbamazepine,
      diphenylhydantoin, or valproate against maximal electroshock may be not dependent
      upon the central NO level. The enhancement of the anticonvulsive action of
      phenobarbital by 7-nitroindazole is probably not related to the decrease of NO in
      the central nervous system.

PMID- 9274971
TI  - Effect of agmatine on spinal nociceptive reflexes: lack of interaction with
      alpha2-adrenoceptor or mu-opioid receptor mechanisms.
AB  - Agmatine has been tested i.v. in alpha-chloralose anaesthetised rats for its
      effects on spinal nociceptive reflexes evoked by mechanical and electrical
      stimuli. Agmatine did not affect reflexes until very high doses (200 mg/kg, i.v.)
      which also caused complex cardiovascular disturbances. In spinally intact rats
      agmatine reduced reflexes; it was slightly less potent when there was carrageenan
      induced hind paw inflammation. The alpha2-adrenoceptor antagonist atipamezole (80
      microg/kg) did not significantly affect these reductions. In spinalised animals,
      agmatine caused a generalised increase in background firing which in animals with
      a non-inflamed paw was significantly reduced after atipamezole. There was no
      significant change in evoked responses once corrected for background activity. In
      all groups of animals agmatine, when administered at various doses and times
      prior to the mu-opioid receptor agonist fentanyl, had no effect on the ID50 of
      fentanyl.

PMID- 9274972
TI  - Differential effects of nipecotic acid and 4,5,6,7-tetrahydroisoxazolo[4,5
      c]pyridin-3-ol on extracellular gamma-aminobutyrate levels in rat thalamus.
AB  - Using the microdialysis technique and HPLC (high-performance liquid
      chromatography) determination of amino acids, the extracellular concentrations of
      gamma-aminobutyrate (GABA), glutamate, aspartate and a number of other amino
      acids were determined in rat thalamus during infusion through the microdialysis
      tubing of the GABA transport inhibitors 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin
      3-ol (THPO) and nipecotic acid. Administration of 5.0 mM THPO led to a 200%
      increase in the extracellular GABA concentration. Simultaneous infusion of THPO
      and GABA (50 microM) increased the extracellular GABA concentration to 1200% of
      the basal level whereas GABA alone was found to increase the GABA level to 500%.
      If nipecotic acid (0.5 mM) was administered together with GABA (50 microM) the
      extracellular concentration of GABA was not increased further. While
      administration of GABA alone or GABA together with nipecotic acid had no effect
      on the extracellular levels of glutamate and aspartate it was found that GABA
      plus THPO increased the extracellular concentration of these amino acids. GABA
      administered alone or together with nipecotic acid or THPO led to relatively
      small but significant increases in the extracellular concentrations of the amino
      acids glycine, glutamine, serine and threonine. The results demonstrate that
      THPO, which preferentially inhibits glial GABA uptake and which is not a
      substrate for the GABA carriers, was more efficient increasing the extracellular
      concentration of GABA than nipocotic acid which is a substrate and an inhibitor
      of both neuronal and glial GABA uptake. This indicates that GABA uptake
      inhibitors that are not substrates for the carrier and which preferentially
      inhibit glial GABA uptake may constitute a group of drugs by which the efficacy
      of GABAergic neurotransmission may be enhanced.

PMID- 9274973
TI  - Central administration of morphine inhibits brain and liver ornithine
      decarboxylase activity in neonatal rats: involvement of transcription- and non
      transcription-dependent mechanisms.
AB  - This study examined whether the developmental deficits usually observed in
      infants born to opiate addicted mothers could involve effects on ornithine
      decarboxylase, a growth-controlling enzyme. Intracerebroventricular (i.c.v.)
      injection of a single dose of morphine (2 microg) to 6-day-old rats markedly
      decreased basal brain and liver ornithine decarboxylase activity as well as the
      increases in hepatic ornithine decarboxylase activity produced by subcutaneously
      (s.c.) administered insulin, an important trophic hormone. Centrally applied
      morphine acts supraspinally to downregulate peripheral ornithine decarboxylase
      activity, since s.c. administration of the same dose as used i.c.v. decreased
      neither basal liver ornithine decarboxylase levels nor tissue responsiveness to
      insulin. This does not imply that the opiate is unable to affect ornithine
      decarboxylase when applied systemically. In fact, a robust inhibition of both
      basal and induced liver ornithine decarboxylase activity was obtained in rat pups
      given 20 microg of morphine s.c. This larger dose is able to trigger the hepatic
      ornithine decarboxylase effects presumably by stimulating opiate receptors
      located at central sites after crossing the blood-brain barrier and penetrating
      into the brain. Concomitant administration of naloxone plus morphine i.c.v.
      prevented morphine from downregulating ornithine decarboxylase activity,
      confirming the participation of supraspinal opioid receptors in morphine
      ornithine decarboxylase actions. Finally, as was the case for insulin induced
      stimulation of ornithine decarboxylase activity, i.c.v. injection of morphine
      markedly diminished insulin induced stimulation of hepatic ornithine
      decarboxylase mRNA accumulation. In turn, contrary to the inhibition of basal
      ornithine decarboxylase activity, morphine did not lower basal hepatic ornithine
      decarboxylase mRNA levels when given alone. Thus, CNS morphine can apparently
      suppress tissue ornithine decarboxylase expression through both transcriptional
      and posttranscriptional mechanisms. The evidence obtained suggest that postnatal
      exposure to opiate drugs might detrimentally affect development by altering
      normal tissue ornithine decarboxylase ontogeny.

PMID- 9274974
TI  - Effect of spinal cyclooxygenase inhibitors in rat using the formalin test and in
      vitro prostaglandin E2 release.
AB  - Spinally delivery of the non-specific cyclooxygenase inhibitor, S(+)-ibuprofen,
      reduces the second phase of the formalin test and the evoked release of
      prostaglandin E2 (prostaglandin E2) from rat spinal cord in vitro. Using two
      selective cyclooxygenase-2 inhibitors, SC58125 (1-[(4-methysufonyl)phenyl]-3-tri
      fluoromethyl-5-(4-fluorophenyl)p yrazole) and SC-236 (4-[5-(4-chlorophenyl)-3
      (trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfon amide), we observed that neither
      agent at the highest dose/concentration employed altered the second phase of the
      formalin test after intrathecal delivery or K+-evoked prostaglandin E2 release
      from spinal cord in vitro, although ibuprofen was effective in both models. These
      observations suggest that cyclooxygenase-2 may not be associated with spinal
      prostanoid synthesis acutely or with facilitated nociception which occurs within
      the limited time frame of the formalin test.

PMID- 9274975
TI  - In vivo binding of (+)-alpha-[3H]dihydrotetrabenazine to the vesicular monoamine
      transporter of rat brain: bolus vs. equilibrium studies.
AB  - The regional rat brain distribution of (+)-alpha-[3H]dihydrotetrabenazine was
      determined following (a) infusion to equilibrium between brain and blood or (b)
      bolus injection. Infusions provide for direct measurement of total distribution
      volumes. The free plus nonspecific distribution volume for the brain was
      determined using infusion of very low specific activity (+)-alpha
      [3H]dihydrotetrabenazine; specific distribution volumes, which represent specific
      radioligand binding, were then calculated as total minus the free + nonspecific
      distribution volume. Both total and specific distribution volumes correlated very
      well (r2 > 0.99) with in vitro distributions of the vesicular monoamine
      transporter binding site. Bolus injection, and measurement of radioactivity at a
      single time point, also provided regional estimates of radioligand binding which
      correlated well (r2 > 0.98) with in vitro values. The bolus method shows a small
      positive bias (+ 10-15%) in regions of high binding site concentrations. Both
      infusion and bolus injection methods give acceptable in vivo measures of (+)
      alpha-[3H]dihydrotetrabenazine binding to the vesicular monoamine transporter of
      rat brain.

PMID- 9274976
TI  - Stimulation of 5-HT1B receptors causes hypothermia in the guinea pig.
AB  - The selective, brain penetrant, 5-HT(1B/D) (formerly 5-HT(1D beta/alpha))
      receptor agonist SKF-99101H (3-(2-dimethylaminoethyl)-4-chloro-5-propoxyindole
      hemifumarate) (30 mg/kg i.p.) causes a dose related fall in rectal temperature in
      guinea pigs which previous studies have shown to be blocked by the non-selective
      5-HT(1B/D) receptor antagonist GR-127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl)
      phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl) [1,1'biphenyl]-4-carboxamide
      oxalate). The present study shows that the hypothermic response to SKF-99101H is
      dose-dependently blocked by SB-224289G (1'-methyl-5-(2'-methyl-4'-[(5-methyl
      1,2,4-oxadiazol-3-yl)bipheny l-4-yl]carbonyl)-2,3,6,7-tetrahydrospiro[furo[2,3
      f]indole-3,4'-pi peridone] hemioxalate) (0.3-10.0 mg/kg p.o.) (ED50 3.62 mg/kg),
      which is the first compound to be described which is more than 60 fold selective
      for the 5-HT1B receptor over the 5-HT1D receptor. SB-216641A (N-[3-(2
      dimethylamino) ethoxy-4-methoxy-phenyl] 2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3
      yl)-(1,1'-biphenyl)-4-car boxamide hydrochloride) (0.6-20.0 mg/kg i.p.), which is
      somewhat less selective (30 fold) for the 5-HT1B receptor over the 5-HT1D
      receptor had a similar effect (ED50 4.43 mg/kg). The brain penetrant 5-HT1D
      selective receptor antagonist, BRL-15572 (4-(3-chlorophenyl)-alpha
      (diphenylmethyl)-1-piperazineethanol+ ++ dihydrochloride) (0.3-100.0 mg/kg i.p.)
      was inactive. When administered alone neither BRL-15572 (0.1-10 mg/kg i.p.) nor
      SB-224289G (2.2-22 mg/kg p.o.) had an effect on body temperature. These data
      demonstrate that 5-HT1B (formerly 5-HT(1D beta)) and not 5-HT1D (formerly 5-HT(1D
      alpha)) receptors mediate the hypothermic response to SKF-99101H (30 mg/kg i.p.)
      in guinea pigs. The compounds described are useful pharmacological tools for
      distinguishing responses to 5-HT1B and 5-HT1D receptors.

PMID- 9274977
TI  - Selective interaction of homophtalazine derivatives with morphine.
AB  - Homophtalazines show specific binding sites in the nigrostriatal system and to
      find their target of action the interactions between these derivatives, nerisopam
      and girisopam, and chlorpromazine, chlordiazepoxide and morphine were assessed.
      The compounds did not influence the chlorpromazine induced decrease in motility
      and catalepsy, nor did they alter the antiaggressive and anticonvulsive action of
      chlordiazepoxide. However, nerisopam and girisopam augmented the agonist potency
      of morphine to induce catalepsy or analgesia; they also altered the opioid
      antagonist potency of naloxone. The naloxone-induced decrease in sucrose
      consumption in drinking water was augmented by nerisopam and girisopam. It is
      suggested that a possible target of action of homophtalazines is the opioid
      signal transduction.

PMID- 9274978
TI  - The effect of angiotensin II receptor antagonists on kidney function in two
      kidney, two-clip Goldblatt hypertensive rats.
AB  - The effect of blockade of the renin-angiotensin system on kidney function using
      non-peptide angiotensin AT1 receptor antagonists was investigated in renovascular
      hypertensive rats. An angiotensin converting enzyme inhibitor, captopril and two
      angiotensin AT1 receptor antagonists, losartan and GR138950 (1-([3-bromo-2[2
      [[(trifluoro-methyl)sulphonyl]amino]phenyl]-5 benzofuranyl]methyl)-4-cyclopropyl
      2-ethyl-1H-imidazole-5-carboxamide) were administered in Na+-deplete two-kidney,
      two-clip Goldblatt hypertensive rats over a 3-day period. Captopril, losartan (30
      mg/kg body weight) and GR138950 (5 mg/kg body weight) significantly (P < 0.001)
      lowered the systolic blood pressure in the hypertensive rats from 290 +/- 5, 252
      +/- 9 and 238 +/- 13 mmHg to 152 +/- 17, 148 +/- 9 and 123 +/- 6 mmHg,
      respectively. The magnitude of reduction in blood pressure in these three groups
      of rats was similar and occurred with comparable marked increases in plasma
      levels of urea and creatinine indicative of acute renal failure. These findings
      demonstrate an important role for angiotensin II in the maintenance of renal
      function during blood pressure reduction in renovascular hypertensive states
      during restriction of dietary Na+ intake.

PMID- 9274979
TI  - Protective effects of CD-832 on organ damage in stroke-prone spontaneously
      hypertensive rats.
AB  - Effects of a newly developed Ca2+ channel antagonist, (4R)-(-)-2
      (nicotinoylamino)ethyl 3 nitrooxypropyl 1,4-dihydro-2,6-dimethyl-4-(3
      nitrophenyl) 3,5-pyridine-dicarboxylate (CD-832), on hypertensive complications
      in stroke-prone spontaneously hypertensive rats (SHRSPs) were compared with
      effects of diltiazem. We examined changes in histological and hematological
      parameters in SHRSPs given the following treatments at 8 to 20 weeks of age: (a)
      CD-832; (b) diltiazem; (c) no treatment. CD-832 and diltiazem were added to the
      diet, in doses of 0.05 and 0.15% (approximately 30 and 100 mg/kg per day),
      respectively, throughout the experimental period. In untreated control SHRSPs,
      systolic blood pressure increased and severe renal lesions such as fibrinoid
      necrosis, smooth muscle proliferation, glomerular and tubular lesions and some
      cardiac fibrosis were observed at age 20 weeks. 12-week repeated-administration
      of CD-832 and diltiazem led to a comparable hypotension and decreased heart rate.
      CD-832 and diltiazem decreased the ratios of weights of kidney and heart to body
      weight and the concentration of blood urea nitrogen and creatinine in serum,
      compared to values in controls. In SHRSPs treated with CD-832 and diltiazem, the
      incidence of renal lesions and myocardial fibrosis was significantly reduced when
      compared with control SHRSPs. These results suggest that 12-week repeated
      administration of CD-832 prevents the development of hypertension and the
      incidence of organ damage in SHRSPs. CD-832 and diltiazem were equally
      efficacious in preventing organ damage but this organ-protective effect was
      obtained at a lower dose for CD-832 (30 mg/kg per day) than that of diltiazem
      (100 mg/kg per day).

PMID- 9274980
TI  - Regulation of ion transport by histamine in mouse cecum.
AB  - Histamine levels are elevated in inflammatory bowel disease. We investigated the
      mechanism by which histamine affects electrolyte transport in the mouse cecum.
      Using the Ussing-chamber voltage clamp technique, histamine was found to cause a
      transient concentration-dependent increase in short-circuit current, a measure of
      total ion transport across the epithelial tissue. This increase was not affected
      by amiloride pretreatment, but was significantly inhibited by bumetanide and
      completely inhibited when chloride was substituted in the bathing buffer by
      gluconate. A histamine-induced increase in short-circuit current was also
      significantly reduced by inhibitors of the cyclooxygenase pathway indicating the
      involvement of prostaglandin E2 in its action. Prostaglandin E2 levels were
      increased in histamine treated tissue and this increase was reversed by
      indomethacin. These data suggest that histamine causes its effect on mouse cecum
      largely through increasing arachidonic acid metabolism resulting in increased
      levels of prostaglandins which in turn increase Cl- secretion in the epithelial
      cells.

PMID- 9274981
TI  - Histaminic bronchospasm potentiated by adenosine: investigation of the
      mechanisms.
AB  - In anaesthetized guinea pigs, adenosine enhances the histamine-induced
      bronchospasm by means of a mechanism partly involving non-adrenergic-non
      cholinergic (NANC) nerves, not related to capsaicin-sensitive neurons (Breschi et
      al., 1994). In the present paper, we excluded any interference by adenosine with
      the mediators known to be present in the airway inhibitory NANC system, VIP
      (vasoactive intestinal polypeptide) and NO (nitric oxide). The use of alpha
      chymotrypsin or L-N(G)-nitro-arginine methyl ester (L-NAME) failed to modify the
      potentiation under study. The effects of adenosine were further investigated by
      studying whether an increased release of excitatory mediators from non-neural
      cells, in particular 5-HT (5-hydroxytryptamine, serotonin) and arachidonic
      products, was involved. In this connection, methysergide did not significantly
      affect the modulatory action of adenosine, revealing that the release of 5-HT was
      also not involved. Inhibition was obtained with hydrocortisone and with
      nordihydroguaiaretic acid, but not with indomethacin or with the mastocyte
      membrane stabilizer, sodium cromoglycate. This evidence suggests that
      lipooxygenase products, not derived from mastocytes, probably participate in the
      potentiating effect of adenosine.

PMID- 9274982
TI  - Nerve stimulation-induced nitric oxide release as a consequence of muscarinic M1
      receptor activation.
AB  - The aim of the present study was to investigate whether nerve stimulation-induced
      nitric oxide (NO) release in the guinea-pig colon is affected by acetylcholine
      and to identify the muscarinic receptor subtype involved. Nerve-smooth muscle
      preparations were suspended in a superfusion chamber and NO/NO2- overflow in the
      superfusate was detected by chemiluminescence analysis. Transmural nerve
      stimulation evoked a significant increase in NO/NO2- release, which was inhibited
      by N(omega)-nitro-L-arginine methyl ester (L-NAME) and abolished by tetrodotoxin.
      Exogenous acetylcholine concentration-dependently increased NO/NO2- release and
      atropine reduced nerve stimulation-evoked NO/NO2- release. The muscarinic M1
      receptor selective antagonist telenzepine (10(-8) M) was as effective as atropine
      (10(-6) M) in inhibiting NO/NO2- release. The muscarinic M3 receptor antagonists
      4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) and para-fluoro
      hexahydrosila-difenidol (p-F-HHSiD) markedly inhibited cholinergic contractions
      at 3 x 10(-8) M and 3 x 10(-7) M respectively, but did not affect NO/NO2-
      release. In conclusion, nerve-induced NO/NO2- release in the guinea-pig colon is
      to a substantial part due to muscarinic M1 receptor activation. Thus
      acetylcholine, a major contractile neurotransmitter in the gut, can release NO
      which could act as a negative feedback mechanism on intestinal smooth muscle or
      neuronal activity.

PMID- 9274983
TI  - Econazole, miconazole and SK & F 96365 inhibit depolarization-induced and
      receptor-operated contraction of guinea-pig isolated trachea in vitro.
AB  - Econazole, miconazole, SK & F 96365 and nifedipine inhibited Ca2+- and
      depolarization-induced and receptor-operated contraction of guinea-pig isolated
      trachea. Econazole, miconazole and SK & F 96365 inhibited histamine- and
      methacholine-induced tracheal contraction more than nifedipine. Nifedipine was
      more potent in inhibiting KCl-induced contraction. Nifedipine, salbutamol and
      theophylline, but not econazole, miconazole or SK & F 96365, relaxed KCl,
      histamine-, and methacholine-precontracted trachea. It appears that in the guinea
      pig tracheal smooth muscle, econazole, miconazole and SK & F 96365 behave
      differently from nifedipine, theophylline and salbutamol. Econazole, miconazole
      and SK & F 96365 are thus introduced as novel antagonists of receptor-operated
      airway smooth muscle contraction.

PMID- 9274985
TI  - Role of mast cell histamine in the formation of rat paw edema: a microdialysis
      study.
AB  - We determined the endogenous histamine concentration in the subplantar space of
      rat hind paws using an in vivo microdialysis technique. A microdialysis probe was
      implanted into the rat hind paw and the histamine content in dialysates was
      measured by high performance liquid chromatography-fluorometry. In wild type
      (+/+) rats, the histamine output (basal level 25.7 +/- 0.9 pmol/ml) increased 115
      , 199- and 426-fold rapidly after subplantar injection of compound 48/80 at doses
      of 0.5, 5 and 50 microg/paw, respectively. In genetically mast cell-deficient
      (Ws/Ws) rats, the basal level of histamine was one third of that obtained from
      +/+ rats, and was not increased by compound 48/80 injection. With this treatment,
      marked, dose dependent, but relatively gradual development of the paw edema was
      found in +/+ rats. However, no edema formation was observed in Ws/Ws rats.
      Histological observations showed neither mast cells nor edema to be present in
      the paw skin of Ws/Ws rats. These findings indicate the critical role of
      histamine as a trigger for the development of edema in vivo. In addition, Ws/Ws
      rats will provide important information as to the roles of mast cells in the
      inflammatory response.

PMID- 9274984
TI  - Dexamethasone, but not stress, induce measurable changes of mitochondrial
      benzodiazepine receptor mRNA levels in rats.
AB  - The expression of the mitochondrial benzodiazepine receptor gene was assayed by a
      semi-quantitative non-radioactive reverse transcriptase polymerase chain reaction
      (RT-PCR) assay. The level of amplified mitochondrial benzodiazepine receptor mRNA
      was expressed as a ratio of either glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) or beta-actin mRNA co-amplified in the same RT-PCR assay. The relative
      amounts of mitochondrial benzodiazepine receptor RNA in several rat tissues were
      found to be similar to the previously reported relative amount of mitochondrial
      benzodiazepine receptor binding sites. The level of these binding sites has also
      been reported to be altered by stress stimuli. In this study we specifically
      measured the effect of stress on the mRNA levels of the mitochondrial
      benzodiazepine receptor as an alternative method to the binding assay in an
      attempt to understand the mechanism by which stress alters binding. Sprague
      Dawley male rats were either forced to swim for 15 min in 18 degrees C water or
      restrained in a plastic cylinder for 45 min either once, or twice daily for 7
      days. Neither the swim stress, nor acute or chronic restraint stress, caused a
      measurable statistically significant relative change in mitochondrial
      benzodiazepine receptor mRNA in the adrenal gland, kidney, testis and olfactory
      bulb. However, daily treatment of rats for 7 days with 4 mg/kg of dexamethasone
      caused a significant decrease in mitochondrial benzodiazepine receptor gene
      expression in adrenal glands. This finding and the measurement of the relative
      levels of mitochondrial benzodiazepine receptor mRNA in the various tissues
      indicate that mitochondrial benzodiazepine receptor density is regulated to some
      extent at the gene expression level. However, the lack of detectable stress
      induced changes in mRNA levels for this receptor seem to indicate that either
      mRNA changes were below detectable levels or that other mechanisms may be
      involved in the previously reported stress-induced changes of mitochondrial
      benzodiazepine receptor density. Because the focus of this work was on the
      regulation of mitochondrial benzodiazepine receptor gene expression, ligand
      binding studies to determine changes in receptor densities were not performed.

PMID- 9274986
TI  - Antiretroviral agent (R)-9-(2-phosphonomethoxypropyl)adenine stimulates cytokine
      and nitric oxide production.
AB  - The immunomodulatory properties of (R)-enantiomer of 9-(2
      phoshonomethoxypropyl)adenine ((R)-PMPA), one of the most potent acyclic
      nucleotide analogs effective against human immunodeficiency virus (HIV), were
      investigated under in vitro conditions using murine peritoneal macrophages.
      Remaining without influence on interferon-gamma and interleukin-2 expression, (R)
      PMPA dramatically stimulated in a concentration- and time-dependent manner the
      secretion of tumor necrosis factor alpha (TNF-alpha) and interleukin-10. It also
      substantially augmented the production of nitric oxide (NO) induced by exogenous
      interferon-gamma. Inhibitory experiments using neutralizing antibodies against
      TNF-alpha and/or interleukin-10 demonstrated that these two cytokines are major
      factors responsible for triggering the underlying mechanism(s) leading to
      enhanced NO production. The novel findings on the immunomodulatory potential of
      acyclic nucleotide analogs are discussed in the context of their possible
      implication in antiviral therapeutic efficacy.

PMID- 9274988
TI  - alpha-Trinositol prevents increased negativity of interstitial fluid pressure in
      rat skin and trachea induced by dextran anaphylaxis.
AB  - The new anti-inflammatory agent alpha-trinositol (D-myo-inositol-1,2,6
      trisphosphate), is suggested to act on the cellular adhesion receptor towards
      extracellular matrix components, the beta1-integrins, and may therefore represent
      a novel principle for therapy of the phenomena associated with acute
      inflammation. Increased negativity of interstitial fluid pressure (p(if)) is a
      major driving force for the rapid edema formation in trachea and skin associated
      with dextran anaphylaxis in the rat. We therefore used this experimental model to
      study the effect of alpha-trinositol in skin and trachea of pentobarbital
      anesthetized rats. p(if) was measured with sharpened glass capillaries (3-7
      microm) connected to a servocontrolled counterpressure system. alpha-Trinositol
      (10 mg) was given before or after dextran. Circulatory arrest was induced 2 min
      after i.v. dextran to limit the increased capillary fluid filtration associated
      with the anaphylactic reaction. This increased filtration will otherwise raise
      interstitial volume and thereby p(if) and cause an underestimation of a potential
      increased negativity of p(if). In the trachea, p(if) was 0.0 +/- 1.0 mmHg (S.D.)
      and -1.4 +/- 0.5 mmHg in controls given saline vehicle and alpha-trinositol (P >
      0.05), respectively, and fell to -8.5 +/- 2.7 mmHg after dextran (P < 0.01).
      alpha-Trinositol given 2 min prior to or after dextran resulted in p(if) of -1.7
      +/- 1.2 mmHg (P > 0.05 versus control, P < 0.01 versus dextran) and -4.7 +/- 3.0
      mmHg (P < 0.01 versus control and dextran), respectively. In skin, i.v. dextran
      caused p(if) to fall from -0.6 +/- 0.5 to -4.6 +/- 1.9 mmHg (P < 0.001). When
      alpha-trinositol was given prior to dextran the corresponding figures were -0.4
      +/- 0.8 and -0.9 +/- 1.1 mmHg, respectively (P > 0.05). Subdermal administration
      of alpha-trinositol after i.v. dextran and circulatory arrest normalized p(if) in
      concentration of 100, 10 and partly at 1 mg/ml. Thus, alpha-trinositol prevented
      the increased negativity of p(if) induced by dextran anaphylaxis when
      administered prior to as well as after dextran showing that the alpha-trinositol
      also could influence an already started inflammatory reaction.

PMID- 9274987
TI  - Mast cell involvement in the rat paw oedema response to 1,8-cineole, the main
      constituent of eucalyptus and rosemary oils.
AB  - The present studies tested the ability of 1,8-cineole to produce inflammatory
      oedema in the hind paw of the rat and verified the possible involvement of mast
      cells in the response. Subplantar injection of 1,8-cineole (10, 15 and 20
      microl/paw) induced a dose-dependent paw oedema which was apparent within 30 min.
      At higher doses the oedema effect was persistent, peaked at 2 h, and then
      decreased gradually but was still pronounced at 24 h post injection. In contrast,
      the oedema produced by mast cell degranulator compound 48/80 (10 microg/paw) had
      a rapid onset with a peak effect at the first hour, followed by a gradual
      decrease thereafter and at 24 h post injection it was almost absent. The oedema
      response to 20 microl 1,8-cineole was significantly inhibited throughout its time
      course in rats pretreated with antihistaminic and antiserotonergic drugs such as
      diphenhydramine, methysergide and cyproheptadine or with ketotifen, a mast cell
      stabilizer. A more effective blockade of the oedema response was, however,
      observed in rats depleted of mast cell granules by systemic treatment with
      compound 48/80. Furthermore, 1,8-cineole was able to cause rat peritoneal mast
      cell degranulation (94%) in vitro, in a concentration as low as 0.3 microl/ml,
      which was almost comparable to that produced by 0.1 microg/ml of compound 48/80.
      The data provide evidence of a key role for the mast cell in 1,8-cineole-induced
      hind paw oedema in the rat.

PMID- 9274989
TI  - Melatonin effects on inhibition of thirst and fever induced by lipopolysaccharide
      in rat.
AB  - In 24 h water deprived rats we have evaluated the effects of melatonin on the
      inhibition of thirst and on fever induced by Escherichia coli lipopolysaccharide.
      Intraperitoneal (i.p) injection of lipopolysaccharide (0.32, 0.64 and 0.96 mg/kg)
      alone induced, a dose-dependent and significant inhibition of water intake as
      well as fever. In addition, lipopolysaccharide at the same concentrations
      increased urinary prostaglandins and serum cytokines levels. On the contrary,
      lipopolysaccharide treatment had no effects on cerebral brain nitric oxide
      synthase activity. All lipopolysaccharide effects were reverted by a prior,
      concomitant and subsequent i.p. treatment with melatonin (2, 4 and 6 mg/kg),
      whereas they were still present when melatonin was injected in combination with
      the melatonin receptor antagonist luzindole (15, 30 and 60 mg/kg, i.p.). We
      suggest that melatonin could exert its dipsogenic effects through a reduction of
      the free radical nitric oxide (NO.) whereas it may reduce body temperature by
      preventing an excessive formation of prostaglandins and cytokines.

PMID- 9274990
TI  - Non-competitive binding of the nonpeptide antagonist BIBP3226 to rat forebrain
      neuropeptide Y1 receptors.
AB  - [3H]Neuropeptide Y labelled neuropeptide Y receptors in rat forebrain membranes
      as a homogenous class of high-affinity sites. Between 80 and 85% of these
      receptors showed high affinity for Y1-selective antagonists such as (R)-N2
      (diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-D-arginine amide (BIBP3226). While
      competitive in functional studies, BIBP3226 produced parallel shifts of the
      Scatchard plots of [3H]neuropeptide Y saturation binding in rat forebrain
      membranes. Mechanisms which are routinely invoked to explain non-competitive
      binding do not apply to BIBP3226. Wash-out experiments, involving successive
      treatment of the membranes with BIBP3226, buffer (wash-out step) and
      [3H]neuropeptide Y, argue against irreversible or a pseudo-irreversible binding
      of the antagonist. Allosteric inhibition is also unlikely since BIBP3226 did not
      affect the rate of dissociation of [3H]neuropeptide Y in isotope dilution
      experiments. The non-hydrolyzable guanine nucleotide, 5'-guanylylimidodiphosphate
      (Gpp(NH)p), abolished the binding of [3H]neuropeptide Y and increased its rate of
      dissociation in isotope dilution experiments. This suggests that the initial
      [3H]neuropeptide Y-receptor association is a low affinity process and that the
      observed binding of [3H]neuropeptide Y is related to the formation of a ternary
      [3H]neuropeptide Y-receptor-G protein complex. Two- or even multistate models (in
      which BIBP3226 could potentially behave as an inverse agonist) could therefore be
      needed to explain the non-competitive antagonism of BIBP3226 in broken cell
      preparations.

PMID- 9274991
TI  - Properties of a new radioiodinated antagonist for human vasopressin V2 and V1a
      receptors.
AB  - A vasopressin receptor antagonist, [1-(beta-mercapto-beta,beta
      pentamethylenepropionic acid), 2-o-ethyl-D-tyrosine, 4-valine, 9-tyrosylamide]
      arginine vasopressin (d(CH2)5[o-ethyl-D-Tyr2,Val4,Tyr-NH9(2)]AVP), has been
      prepared. This antagonist is a potent antiantidiuretic, antivasopressor and
      antioxytocic peptide with pA2 values of 7.69-7.94 and affinities of 1.12-11.0 nM.
      When radioiodinated at the phenyl moiety of the tyrosylamide residue at position
      9, this peptide was demonstrated to bind to vasopressin V2 and V1a receptors with
      a dissociation constant of 0.22-0.75 nM. This ligand is a good tool for further
      studies on human vasopressin V2 receptor localization and characterization, when
      used in combination with a selective vasopressin V1a ligand.

PMID- 9274992
TI  - Effects of sematilide, a novel class III antiarrhythmic agent, on membrane
      currents in rabbit atrial myocytes.
AB  - The effects of sematilide, a novel class III antiarrhythmic agent, on membrane
      currents were examined in single myocytes isolated from the rabbit left atrium,
      using the whole-cell voltage clamp technique. Application of 10, 30, 100 and 300
      microM sematilide caused a concentration-dependent inhibition of the delayed
      rectifier K+ current (IC50 approx. 25 microM). The sematilide-sensitive current,
      which was recorded by means of a triangular voltage command, showed a strong
      inward rectification and had a peak at about -40 mV, suggesting that sematilide
      inhibits the rapidly activating delayed rectifier K+ current. The Ca2+
      independent transient K+ and the inward rectifier K+ currents were not affected
      significantly by application of 100 microM sematilide. Moreover, voltage
      dependent Na+ and Ca2+ currents were not affected significantly by 100 microM
      sematilide. These findings indicate that sematilide selectively blocks the
      rapidly activating delayed rectifier K+ current in atrial myocytes and provide
      evidence supporting the usefulness of the drug as a class III antiarrhythmic
      agent.

PMID- 9274993
TI  - Electrophysiological effects of various neuroactive steroids on the GABA(A)
      receptor in pituitary melanotrope cells.
AB  - The action of steroids on the bioelectrical response to gamma-aminobutyric acid
      (GABA) has never been studied in pituitary cells. In the present study, we have
      thus investigated the effects of a series of neuroactive steroids on the GABA
      activated current in frog melanotrope cells in primary culture, using the patch
      clamp technique in the whole-cell configuration. Bath perfusion of 3alpha-isomers
      of pregnanolone or tetrahydrodeoxycorticosterone (1 microM) significantly
      enhanced the current evoked by short pulses of GABA (3 microM) and accelerated
      its desensitization. In contrast, the 3beta-isomers (30 microM) had no effect on
      the GABA-activated current. Addition to the bath solution of
      dehydroepiandrosterone or dehydroepiandrosterone sulfate (10 microM) inhibited
      the GABA-activated current without modifying its kinetics while pregnenolone
      sulfate (10 microM) both inhibited the GABA-activated current and accelerated its
      decay rate. The effects of pregnane steroids were not impaired by the central
      type benzodiazepine receptor antagonist flumazenil (10 microM). In conclusion,
      the present study reveals that neuroactive steroids may exert multiple modulatory
      activities on the GABA(A) receptor borne by melanotrope cells. The effect of
      steroids on the current evoked by GABA is rapid, reversible, stereospecific and
      not mediated through the benzodiazepine binding site of the GABA(A) receptor.

PMID- 9274994
TI  - Stimulation of neuropeptide Y release in rat pheochromocytoma cells by nitric
      oxide.
AB  - Neuropeptide Y and nitric oxide (NO) synthase are colocalized in nervous tissues.
      We tested the hypothesis whether or not NO might be involved in the release of
      neuropeptide Y. Neuropeptide Y concentration in the supernatant of PC12 rat
      pheochromocytoma cells, shown to express NO synthase I by immunohistochemistry,
      rose threefold in a time- and dose-dependent manner following sodiumnitroprusside
      and 3-morpholinosydnonimine (SIN-1) incubation. Neuropeptide Y mRNA expression
      was induced by NO-donors as a function of incubation-time. Neuropeptide Y
      production rose fivefold with zaprinast, an inhibitor of the phosphodiesterase V
      and threefold with nerve growth factor (NGF). Combined application of zaprinast
      and NGF did not further increase neuropeptide Y production while combination of
      zaprinast and sodiumnitroprusside potentiated the NO effect on neuropeptide Y
      release. The data suggest that NO regulates neuropeptide Y secretion of PC12
      pheochromocytoma cells on the mRNA level.

PMID- 9274995
TI  - Uncompetitive inhibition of [3H]1,3-di-o-tolyl-guanidine-defined sigma binding
      sites by desipramine, propranolol and alprenolol in rat brain.
AB  - Desipramine, imipramine, clomipramine, (-)-propranolol, (-)-alprenolol, (+/-)
      pentazocine and risperidone caused a concentration-dependent inhibition of 6 nM
      [3H]DTG (1,3-di-o-tolylguanidine)-defined sigma (sigma) binding with Ki values of
      about 0.5-2.5 microM in well-washed homogenates obtained from rat cerebral
      cortex. The saturation studies revealed that the inhibition by desipramine (1-4
      microM), (-)-propranolol (1 microM) and (-)-alprenolol (3 microM) resulted from a
      reduction of the Bmax value without alteration of the Kd of [3H]DTG binding to
      the cortex or hippocampus. In contrast, imipramine, (+/-)-pentazocine,
      clomipramine and risperidone competitively attenuated the cortical or hippocampal
      [3H]DTG binding. These findings demonstrate the uncompetitive inhibition of
      [3H]DTG binding by neuroactive drugs, thereby providing further support for the
      possible multiple regulation of cerebral sigma receptors.

PMID- 9274996
TI  - Differential effects of nitrofurans on the production/release of steroid hormones
      by porcine adrenocortical cells in vitro.
AB  - Changes in the biogenesis of corticosteroids caused by nitrofurans were studied.
      The three nitrofurans used: furazolidone, furaltadone and nitrofurantoin, altered
      the steroid production/release by porcine adrenocortical cells in vitro during 1
      h incubations. With pregnenolone as a substrate the nitrofurans inhibited
      aldosterone production/release. Although the nitrofurans differed in potency
      (nitrofurantoin > furazolidone > furaltadone) maximum inhibition occurred at 100
      microM. In this concentration the nitrofurans changed also the release/production
      of other corticosteroids. The output of corticosterone and cortisol decreased by
      50%. The production/release of deoxycortisol stayed the same. In contrast the
      output of progesterone and 17alpha-hydroxyprogesterone increased to more than
      200% of control. The nitrofurans slightly reduced the output of androstenedione.
      No significant increases of the production/release of other steroids
      (testosterone, dehydroepiandrosterone, estradiol-17beta and estrone) by the cell
      suspension could be observed. The profile of the nitrofuran-induced changes lead
      to the conclusion that nitrofurans interfere with mitochondrial enzymes. These
      enzymes, presumably cytochrome P450(11,18) mediate the hydroxylation and the
      oxidation at C11 and C18, the final steps in the biogenesis of aldosterone,
      corticosterone and cortisol. The rapid and reversible fall in the output of these
      steroids occurs in vitro at concentrations which are below therapeutic blood
      concentrations seen in vivo. At higher concentrations the nitrofurans hinder the
      biogenesis of androgens. Thus nitrofurans can also affect steps in the steroid
      biogenesis located in the endoplasmatic reticulum.

PMID- 9274997
TI  - RBI-257: a highly potent dopamine D4 receptor-selective ligand.
AB  - RBI-257 (1-[4-iodobenzyl]-4-[N-(3-isopropoxy-2-pyridinyl)-N-methyl]-aminopiperid
      ine), the p-iodobenzyl analog of U-101,958 (1-benzyl-4-[N-(3-isopropoxy-2
      pyridinyl)-N-methyl]-aminopiperidine) had a lower dissociation constant (Ki = 0.3
      vs. 2.7 nM) and higher selectivity than U-101,958 at dopamine D4 receptors, over
      dopamine D2 and D3 receptors in transfected cell membranes and D2-like sites in
      rat forebrain. Dopamine D4 receptor affinity of iodo-isomers of RBI-257 ranked:
      para > meta > ortho. RBI-257 had much lower affinity at D1 and D5 dopamine
      receptors in transfected cells, as well as dopamine D1-like receptors, alpha1,
      alpha2 or beta(1,2) adrenoceptors, sigma(1,2) receptors and 5-HT1A or 5-HT2A
      receptors, and transporters for dopamine, norepinephrine or serotonin in rat
      forebrain tissue. RBI-257 may be a useful probe or radioligand for brain dopamine
      D4 receptors.

PMID- 9274998
TI  - Spontaneous Mn2+ entry is specifically inhibited by calyculin A in human leukemic
      HL-60 cells.
AB  - The effects of calyculin A and other agents which enhance protein Ser/Thr
      phosphorylation, on the cytosolic free Ca2+ concentration ([Ca2+]i) and
      spontaneous Mn2+ entry were investigated in fura-2-loaded human leukemic HL-60
      cells. Calyculin A (30 nM), a specific inhibitor of protein Ser/Thr phosphatase
      (PP) 1 and 2A, significantly decreased [Ca2+]i. By contrast, another structurally
      unrelated inhibitor of PP1 and 2A, okadaic acid (1 microM), caused a slight
      elevation in [Ca2+]i. Forskolin (30 microM), which could enhance protein kinase A
      activity by raising cAMP concentration, also caused a rise in [Ca2+]i. Phorbol
      myristate acetate (PMA, 300 nM), an activator of protein kinase C, did not have a
      significant effect on [Ca2+]i. Spontaneous entry of Mn2+ (a surrogate ion for
      Ca2+) was strongly inhibited by calyculin A, but not okadaic acid, forskolin or
      phorbol myristate acetate. Such inhibition was not significantly affected by
      staurosporine (300 nM), a non-specific inhibitor of protein Ser/Thr kinases. Our
      results suggest that calyculin A inhibited a plasmalemmal leak pathway to Mn2+
      (and Ca2+), probably leading to a decrease in [Ca2+]i. Inhibition of spontaneous
      Mn2+ entry by calyculin A may depend on a specific protein phosphorylation
      pattern induced by staurosporine-insensitive protein kinase(s).

PMID- 9274999
TI  - Innovative approaches to the treatment of advanced breast cancer: introduction.

PMID- 9275000
TI  - Evolving concepts in the systemic drug therapy of breast cancer.
AB  - Experimental and clinical observations of the proliferation of cancer cells and
      their responses to cytotoxic drugs already have had an impact on the design of
      anticancer therapies and it is possible that further understanding of the natural
      history of tumors will enable better treatments to be developed. This review
      addresses several approaches to improving the prognosis for patients with breast
      cancer in which our understanding of tumor dynamics plays an important role.
      Increasing dose intensity can be achieved by dose escalation (increasing the
      amount of drug) or increasing dose density (reducing the time between
      treatments). The Gompertzian model of tumor growth, which is concordant with many
      experimental and clinical observations, can offer an explanation why, although
      dose escalation improves the number of clinical responses, cure is still
      uncommon. In the Gompertzian model, smaller tumors grow faster, so tumor regrowth
      between treatment cycles is more rapid when cell kill is greatest. Reducing the
      time available for tumor regrowth (increasing dose density), which is now
      possible through the use of colony-stimulating factors to hasten hematopoietic
      recovery, may have a greater impact on clinical outcome than dose escalation.
      Sequential schedules allow optimal doses to be used in dose-dense cycles. Several
      cycles of the optimal dose of agent A, followed by several cycles of the optimal
      dose of agent B, may be more effective than the simultaneous combination of
      suboptimal doses of A and B. In this context, agents A and B may be single agents
      or established combinations. This tactic allows new agents, such as the taxoids,
      to be used in conjunction with established therapies, such as doxorubicin plus
      cyclophosphamide, at optimal doses in dose-intensive regimens. Although such
      regimens may maximize cytoreduction, this may not be sufficient to improve
      significantly the long-term outcome for patients with breast cancer. A recent
      trial using high-dose consolidation chemotherapy with autologous bone marrow
      support has thrown doubt on the assertion, implicit in Gompertzian cytodynamics,
      that optimal cytotoxic therapy can kill all tumor cells. The results of this
      trial suggest that a consistent number of tumor cells remain whether high-dose
      chemotherapy with autologous bone marrow support is used in patients in complete
      pathologic remission or in patients with overt relapse. If there is a lower limit
      to cytoreduction, other approaches must be developed to control or prevent the
      regrowth of residual tumor cells. This will require a better understanding of the
      molecular biology of breast cancer and the ability to predict and assess the
      sensitivity of individual patient's tumors to particular therapies. Factors such
      as HER2 overexpression are already being linked to sensitivity to particular
      agents and the products of oncogenes such as HER2 may be targeted by biologic
      therapies such as monoclonal antibodies. Furthering our understanding of the
      biology and behavior of tumor cells may lead to significant improvements in the
      long-term prognosis for patients with early and advanced breast cancer.

PMID- 9275001
TI  - Anthracycline resistance: the problem and its current definition.
AB  - Anthracyclines were introduced for the treatment of breast cancer in the 1970s
      and were considered the most active single agents until the recent introduction
      of the taxoids. Although incorporation of anthracyclines into combination
      regimens has been shown to improve clinical outcomes, the duration of response
      and survival in women with metastatic disease is still modest, and 50% of women
      treated with adjuvant chemotherapy eventually relapse. Intrinsic and acquired
      drug resistance, leading to untreatable disease, are fundamental reasons for
      clinical failure in breast cancer, but the clinical relevance of the various
      known mechanisms of drug resistance is not clear. P-glycoprotein (Pgp)-mediated
      multidrug resistance, the most studied form of anthracycline resistance, can be
      inhibited by a variety of chemicals. While in vitro studies have demonstrated the
      efficacy of some Pgp inhibitors, and led to the development of more clinically
      acceptable agents, clinical studies have not shown a consistent advantage in
      using Pgp inhibitors. Since Pgp is a physiologic efflux mechanism, consideration
      also should be given to the possible consequences of its inhibition. Studies with
      Pgp knock-out transgenic mice suggest that Pgp is not essential for life, but
      that Pgp inhibition may make some tissues, such as the brain, more vulnerable to
      cytotoxic drugs. Correlating overexpression of the MDR1 gene in human tumor
      samples with treatment failure has not proved straightforward, and further
      studies are needed to clarify the contribution of multidrug resistance mechanisms
      to clinical anthracycline resistance. Mechanisms other than drug efflux pumps,
      which may contribute to anthracycline resistance, include changes in
      topoisomerase II, the major cellular target of anthracyclines. There remains a
      gulf between the laboratory definitions of drug resistance, which can be
      elucidated in great detail, and the clinical definition, which is based on the
      time to treatment failure. New drugs still need to be assessed empirically in the
      clinic, and these results may then be correlated with laboratory findings. We
      cannot yet reliably predict clinical efficacy, cross-resistance, or the
      mechanisms responsible for treatment failure from laboratory studies.

PMID- 9275002
TI  - Docetaxel (Taxotere) for the treatment of anthracycline-resistant breast cancer.
AB  - Until the introduction of the taxoids, docetaxel (Taxotere; Rhone-Poulenc Rorer,
      Antony, France) and paclitaxel (Taxol; Bristol-Myers Squibb Oncology, Princeton,
      NJ), in the 1990s, anthracyclines were widely recognized as the best single
      agents for the treatment of breast cancer. However, even when anthracyclines are
      used in combination regimens with response rates of over 50%, including complete
      responses in 17% of patients, few women (3%) with metastatic disease remain
      disease free at 5 years after treatment. The low level of sustained responses is
      largely due to the phenomenon of drug resistance. Anthracycline resistance often
      involves multidrug resistance efflux mechanisms, but also can involve factors
      affecting topoisomerase II and apoptosis. When combining other cytotoxic agents
      with anthracyclines, it is of value to use non-cross-resistant drugs so that the
      induction of anthracycline-resistance mechanisms does not also affect the
      efficacy of other agents in the combination therapy. Clinical studies have shown
      that docetaxel, which is highly active against metastatic breast cancer as a
      single agent, has a high level of non-cross-resistance with anthracyclines. The
      overall response rate to docetaxel monotherapy in patients with anthracycline
      resistant or refractory metastatic disease has been shown to be 41%. The response
      rate to first-line docetaxel monotherapy for metastatic breast cancer has been
      shown to be 61%, suggesting that two thirds of the activity of docetaxel is
      retained in anthracycline-resistant disease. Treatment with a simultaneous
      combination of docetaxel and doxorubicin has been found to be very active, with a
      response rate of 89%, and trials to exploit the lack of cross-resistance between
      these agents, in sequential regimens and adjuvant therapies, are under way.

PMID- 9275003
TI  - Patient benefits from new treatment options and schedules for breast cancer.
AB  - Adjuvant chemotherapy is of proven survival benefit for patients with early
      breast cancer, but trials of new adjuvant therapies take many years to conduct
      and evaluate. In addition, adjuvant chemotherapy is given "blind," with no prior
      knowledge of the sensitivity of a patient's tumor to the agents being used.
      Primary chemotherapy is an innovative approach in which chemotherapy is given as
      first-line treatment, before surgery. This approach was developed for tumor
      reduction in inoperable locally advanced breast cancer, and the results obtained
      in several studies suggested that primary chemotherapy with adjuvant surgery
      could be an effective alternative to the conventional approach of primary surgery
      with adjuvant chemotherapy. Several combination regimens have proved successful
      as primary chemotherapy, with response rates of 69% to 78%, including 12% to 30%
      complete remissions. The use of infusional 5-fluorouracil, in combination with
      bolus injections of epirubicin and cisplatin (infusional ECF), as primary
      chemotherapy in women with metastatic or locally advanced breast cancer has been
      pioneered by The Royal Marsden NHS Trust in the United Kingdom. Infusional ECF
      has shown a response rate of 98%, with 66% complete remissions, in a trial
      involving 50 women with large operable breast tumors. Infusional ECF is now being
      compared with conventional doxorubicin/cyclophosphamide chemotherapy in a
      multicenter trial. Administering chemotherapy before surgery also allows the drug
      sensitivity of the tumor to be assessed at the time of treatment. Techniques for
      testing the chemosensitivity of tumors in vivo and adjusting the chemotherapy in
      line with initial results are being investigated. In this way, primary
      chemotherapy may offer an effective approach to testing new therapies as front
      line treatments.

PMID- 9275004
TI  - Future perspectives of docetaxel (Taxotere) in front-line therapy.
AB  - The recognition that early breast cancer is a systemic disease has led to the
      development of multimodal treatments incorporating adjuvant hormonal and
      chemotherapies. Adjuvant strategies have improved the outcome of treatment for
      early breast cancer, but 50% of women still relapse and develop overt metastatic
      disease, which is largely incurable. In the search for more effective
      chemotherapies, the taxoid, docetaxel (Taxotere; Rhone-Poulenc Rorer, Antony,
      France), has demonstrated high single-agent activity against metastatic breast
      cancer, including visceral metastases, and is now in phase III trials of
      combination adjuvant and front-line therapies. When cytotoxic drugs are used in
      combination, it is important to consider the dose-response relationships and the
      toxicity profiles of the agents involved. It often is necessary to reduce the
      doses of drugs given in combination to avoid excessive toxicity; this may result
      in the administration of suboptimal doses. Early clinical studies have shown that
      therapeutic doses of docetaxel (60 to 100 mg/m2) can be used in combinations with
      doxorubicin, 5-fluorouracil, cyclophosphamide, ifosfamide, vinorelbine, and
      cisplatin. The most frequent adverse effect of docetaxel is neutropenia (91% of
      patients), but other effects, such as neurosensory changes and fluid retention,
      also must be taken into consideration when planning combination therapies. It may
      be possible to ameliorate some toxicities by preventive measures. Fluid
      retention, which generally occurs at cumulative doses greater than 500 mg/m2, has
      been shown to be reduced in severity and delayed in onset by prophylactic
      corticosteroid treatment from the day before each docetaxel administration for 3
      to 5 days. Neutropenia may be reduced by treatment with granulocyte colony
      stimulating factor, and neurotoxicity may be reduced by protectants such as
      amifostine. These strategies are under investigation. The high single-agent
      activity of docetaxel makes it an excellent candidate for treatments such as
      induction regimens before high-dose chemotherapy and adjuvant therapies. Short
      term treatment regimens such as these should also avoid the cumulative toxicities
      of docetaxel. It is important that new drugs, such as docetaxel, which have shown
      promising activity against metastatic disease and could have a significant impact
      on the natural history of early breast cancer, are investigated as front-line
      treatments.

PMID- 9275006
TI  - The effects of acid glycosaminoglycans on neonatal calvarian cultures--a role of
      keratan sulfate in Morquio syndrome?
AB  - Morquio syndrome (mucopolysaccharidosis IV) presents with multiple bone dysplasia
      and is characterized by the inability to degrade keratan sulfate due to deficient
      N-acetylgalactosamine-6-sulfate sulfatase in Morquio A syndrome and deficient
      beta-D-galactosidase in Morquio B syndrome. The aim of our study was to
      investigate into the pathogenetic mechanism as it is not clear whether the
      accumulation of keratan sulfate is toxic for osteoblasts or inhibits osteoblast
      activity as e.g. bone resorption. The glycosaminoglycans keratan sulfate, heparan
      sulfate, dermatan sulfate, chondroitin-4,6-sulfate and hyaluronic acid were
      tested in rat neonatal calvarian cultures for their effects on bone resorption,
      osteoblast activity and toxicity. Bone resorption was evaluated by calcium
      release into the medium, osteoblast activity by the determination of alkaline
      phosphatase and toxicity by measuring lactate dehydrogenase in the culture media.
      Keratan sulfate had no effect on bone resorption but inhibited osteoblast
      activity at the low, nontoxic concentration of 10 ng per ml organ culture
      supernatant significantly (p<0.05). At a concentration of 100 ng per ml keratan
      sulfate revealed toxic effects as reflected by significantly (p<0.05) elevated
      lactate dehydrogenase activity. None of the other glycosaminoglycans inhibited
      osteoblast activities. Heparan sulfate showed at toxic levels (10 microg per ml
      supernatant) significantly increased bone resorption (p<0.05) accompanied by
      increased alkaline phosphatase activity. The specific keratan sulfate effects of
      inhibiting osteoblast activity and toxicity towards bone, which were never tested
      before, suggest a role for this glycosaminoglycan in the pathogenesis of bone
      dysplasia in Morquio syndrome.

PMID- 9275005
TI  - The Gaboon viper, Bitis gabonica: hemorrhagic, metabolic, cardiovascular and
      clinical effects of the venom.
AB  - The effects of Bitis gabonica venom have been studied in several animal species,
      including the monkey, dog, rabbit, rat and guinea pig. Further information has
      been provided by observations on the effects of snake bite in man. Bitis gabonica
      venom exerts a number of cytotoxic and cardiovascular effects: cytotoxic effects
      include widespread hemorrhage, caused by the presence of two hemorrhagic
      proteins. These hemorrhagins bring about separation of vascular endothelial cells
      and extravasation of blood into the tissue spaces. Metabolic alterations include
      decreased oxygen utilization by tissues and increased plasma glucose and lactate
      concentrations. Metabolic non-compensated acidosis has also been seen in the rat
      as a consequence of the cytotoxicity of the venom. Cardiovascular effects include
      disturbances in atrio-ventricular conduction and reduction in amplitude and
      duration of the action potential brought about by a decreased calcium membrane
      conductance. A progressive decrease in myocardial contractility can also be
      attributed to the decreased calcium conductance, which together with the severe
      acidosis may cause death in experimental animals. A severe, though reversible,
      vasodilatation was observed after envenomation due to unidentified compounds in
      the venom. In man, envenomation causes a variable clinical picture depending on
      the time course and severity of envenomation. Frequently seen effects include
      hypotension, hemorrhage at the site of the bite and elsewhere and disseminated
      intravascular coagulation. Envenomation can be satisfactorily treated with
      antivenom.

PMID- 9275007
TI  - Modulation of human T lymphocyte proliferation by 4-hydroxynonenal, the bioactive
      product of neutrophil-dependent lipid peroxidation.
AB  - The proliferative capacity of immune cells is known to be sensitive to conditions
      of oxidative stress and lipid peroxidation. We tested the hypothesis that
      activated neutrophils can induce peroxidation in extracellular lipid substrates,
      and evaluated the effects of 4-hydroxy-2,3-trans-nonenal (4-HNE)--the most
      reactive aldehydic product of lipid peroxidation--on mitogen-induced
      proliferation of human T lymphocytes. Neutrophils activated in the presence of
      extracellular lipid substrates (liposomes, cellular membranes) induced lipid
      peroxidation. By means of cytoimmunofluorescent labeling and confocal microscopy,
      the binding of 4-HNE to surface and cytoplasmic proteins of activated neutrophils
      was observed. Short (20 min) pre-treatment of cells with low concentrations of 4
      HNE were able to dose-dependently decrease the proliferation of human peripheral
      blood lymphocytes challenged with PHA or anti-CD3 monoclonal antibody OKT3, as
      well as the proliferation of a tetanus specific human T-cell line challenged with
      tetanus toxoid. In these conditions, the binding of 4-HNE to surface and
      cytoplasmic proteins of lymphocytes was also observed. When the proliferative
      capacity of peripheral blood lymphocytes was monitored over several days after 4
      HNE treatment and PHA challenge, a recovery and a rebound in cell proliferation
      was observed. Data reported indicate that the lipid peroxidation promoted by
      activated neutrophils can exert modulatory effects on the responsivity of human T
      cells, through the action of its most reactive product, 4-HNE.

PMID- 9275008
TI  - Irreversible binding of N-methyl-N-[(1S)-1-(4-isothiocyanatophenyl)-2-(1
      pyrrolidinyl)ethyl-3,4 -dichlorophenylacetamide to the cloned rat kappa opioid
      receptor.
AB  - N-Methyl-N-[(1S)-1-(4-isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl-3,4-
      dichlorophenylacetamide (MITPD), is an isothiocyanate derivative of the kappa
      agonist ICI-199,441. In this study, interaction of MITPD with cloned mu, delta,
      and kappa opioid receptors was characterized. MITPD inhibited [3H]diprenorphine
      binding to kappa receptors with high affinity and with approximately 700- and
      approximately 870-fold selectivity over mu and delta receptors. Pretreatment with
      MITPD followed by extensive washing reduced kappa receptor binding with an IC50
      value of 3.7 nM, but did not affect mu or delta binding at < or = 0.1 microM.
      Preincubation with 1 microM MITPD abolished [3H]diprenorphine binding, while
      pretreatment with 1 microM ICI-199,441 increased Kd of [3H]diprenorphine binding
      with no change in Bmax. Thus, MITPD is a selective kappa irreversible ligand. The
      region of the kappa receptor that conferred selectivity for MITPD was determined
      by examining its binding to four mu/kappa chimeras. IC50 values of MITPD for
      inhibition of [3H]diprenorphine binding were determined to be 430 nM for Chimera
      III (kappa1-141/mu151-398), 1.8 nM for Chimera IV (mu1-150/kappa142-380), 40 nM
      for Chimera XI (mu1-268/kappa263-380) and 14 nM for Chimera XII (kappa1-262/mu269
      398). Pretreatment with MITPD followed by extensive washing reduced binding to
      chimera IV with an IC50 value of 75 nM, but did not affect III, XI or XII binding
      (IC50 >1 microM). Thus, the region from the third transmembrane helix to the C
      terminus of the kappa receptor is important for the binding of MITPD.

PMID- 9275010
TI  - Stimulation by alpha-lipoic acid of glucose transport activity in skeletal muscle
      of lean and obese Zucker rats.
AB  - Alpha-lipoic acid (ALA), a potent biological antioxidant, improves insulin action
      of skeletal muscle glucose transport and metabolism in both human and animal
      models of insulin resistance. In order to obtain further insight into the
      potential intracellular mechanisms for the action of ALA on insulin-stimulated
      glucose transport in skeletal muscle, we investigated the effects of direct
      incubation with ALA (2 mM) on 2-deoxyglucose (2-DG) uptake by epitrochlearis
      muscle from either insulin-sensitive lean (Fa/-) or insulin-resistant obese
      (fa/fa) Zucker rats. ALA stimulated 2-DG uptake in muscle of lean animals by 76%,
      whereas ALA stimulated 2-DG uptake by only 48% in muscle from obese animals. The
      stimulation of 2-DG uptake due to ALA was enhanced 30-55% in the presence of
      insulin. In contrast, ALA action on 2-DG uptake was not additive with the effects
      of electrically-stimulated muscle contractions in either insulin-sensitive or
      insulin-resistant muscle. Wortmannin (1 microM), an inhibitor of
      phosphotidylinositol-3-kinase, completely inhibited insulin action on 2-DG
      uptake, but inhibited ALA action by only 25%. Collectively, these results
      indicate that although a portion of ALA action on glucose transport in mammalian
      skeletal muscle is mediated via the insulin signal transduction pathway, the
      majority of the direct effect of ALA on skeletal muscle glucose transport is
      insulin-independent.

PMID- 9275011
TI  - Tolerance to lipopolysaccharide is not related to the ability of the hypothalamus
      to produce prostaglandin E2.
AB  - The effects of repeated administration of Escherichia coli lipopolysaccharide
      (LPS) on body temperature and hypothalamic prostaglandin E2 (PGE2) production was
      examined in male Sprague-Dawley rats to elucidate whether the development of
      endotoxin tolerance is related to the ability of the hypothalamus to produce
      PGE2. Initial injection of LPS resulted in hyperthermia, preceded by short-termed
      hypothermia, while no changes in body temperature were observed after the second
      injection (administered 48 h later). In contrast, LPS induced elevation in
      hypothalamic PGE2 production after both the first and second injections of the
      pyrogen. This led us to conclude that endotoxin tolerance is independent of the
      hypothalamic production of PGE2 in response to repeated administration of LPS.

PMID- 9275009
TI  - KB-R7785, a novel matrix metalloproteinase inhibitor, exerts its antidiabetic
      effect by inhibiting tumor necrosis factor-alpha production.
AB  - It has been suggested that tumor necrosis factor-alpha (TNF-alpha) is a key
      mediator of insulin resistance in non-insulin-dependent diabetes mellitus
      (NIDDM). TNF-alpha is synthesized as a membrane-bound precursor; this is
      proteolytically processed to an active form by a matrix metalloproteinase (MMP)
      like enzyme. In this study, we have used KKAy mice which show insulin resistance
      like NIDDM to investigate the effects of KB-R7785, a novel MMP inhibitor, on
      blood glucose and insulin levels. Subcutaneous administration of KB-R7785 at 100
      mg/kg twice daily (i.e., 200 mg/kg/day) for 4 weeks resulted in a significant
      decrease in plasma glucose levels which was observed after 3 weeks. Oral
      administration of pioglitazone (20 mg/kg twice daily or 40 mg/kg/day for 4
      weeks), an agent known to ameliorate insulin sensitivity, significantly decreased
      plasma glucose levels during the treatment period. KB-R7785, but not
      pioglitazone, also significantly decreased plasma insulin levels.
      Lipopolysaccharide (LPS) increased plasma TNF-alpha levels to a significantly
      greater degree in KKAy mice than in normal C57BL mice; this was inhibitable in
      KKAy mice by KB-R7785. In contrast, pioglitazone did not affect the LPS-induced
      increase in plasma TNF-alpha levels in KKAy mice. These results suggest that KB
      R7785 exerts its antidiabetic effect by ameliorating insulin sensitivity through
      the inhibition of TNF-alpha production.

PMID- 9275012
TI  - Refined electrophysiological analysis suggests that a depressant toxin is a
      sodium channel opener rather than a blocker.
AB  - The effects of a recombinant depressant insect toxin from Leiurus quinquestriatus
      hebraeus, Lqh IT2-r, have been studied in current and voltage-clamp conditions on
      the isolated axonal and DUM neuron preparations of the cockroach Periplaneta
      americana. Lqh IT2-r depolarizes the axon, blocks the evoked action potentials,
      and modifies the amplitude and the kinetics of the sodium current. The inward
      transient peak current is greatly decreased and is followed by a maintained slow
      activating-deactivating sodium current. The slow component develops at membrane
      potentials more negative than the control, and has a time constant of activation
      of several tens of milliseconds. The flaccid properties of Lqh IT2-r do not
      correspond to a blockage of the Na+ channels, but may be attributed to modified
      Na+ channels which open at more negative potential, activate slowly and do not
      inactivate normally.

PMID- 9275013
TI  - Inhibitory effects of various spasmolytics on the vagal afferent gastric
      excitatory response in cats.
AB  - The inhibitory effects of atropine, cimetropium, pirenzepine and N
      butylscopolamine on the vagal afferent gastric excitatory response in cats under
      anesthesia with pentobarbital sodium and infusion of gallamine were examined.
      Electrical stimulation of vagal trunk in left side (10 Hz in frequency, 3 msec in
      duration, 15 V in intensity and for 10 sec) caused an initial gastric excitatory
      response during the period of stimulation followed by a late excitatory gastric
      response after stimulation in normal cats. The initial response was inhibited by
      atropine (100 microg/kg, i.v.) and hexamethonium (10 mg/kg, i.v.), while the late
      response was inhibited by atropine but not by hexamethonium (10 mg/kg, i.v.). In
      chronic supranodose vagotomized cats 11-15 days after the operation, stimulation
      of the vagal trunk caused a late gastric excitatory response after the
      stimulation period, which was inhibited by atropine (100 microg/kg, i.v.) but not
      by hexamethonium (10 mg/kg, i.v.). The two types of gastric responses in normal
      cats have been defined as follows: the initial gastric excitatory response
      (atropine- and hexamethonium- sensitive) is due to activation of vagal efferent
      fibers and the late gastric excitatory response (atropine-sensitive and
      hexamethonium-resistant) is due to activation of vagal afferent fibers. ED50
      values of atropine, cimetropium, pirenzepine and N-butylscopolamine in inhibiting
      the vagal afferent gastric response were 7.2 microg/kg (n=4), 2.4 microg/kg
      (n=6), 82.6 microg/kg (n=3) and 93.0 microg/kg (n=4), respectively. The
      inhibitory effects of atropine and cimetropium on the vagal afferent gastric
      excitatory response (hexamethonium-resistant) were more potent than those of
      pirenzepine and N-butylscopolamine. These results suggested that the potent
      inhibitory effects of cimetropium and atropine on the vagal afferent gastric
      response may involve a potent spasmolytic effect.

PMID- 9275015
TI  - Circadian rhythm of fever induced by interferon-alpha in mice.
AB  - The influence of dosing time on the fever induced by interferon-alpha (IFN-alpha)
      was investigated in ICR male mice under light-dark cycle. There was a significant
      circadian rhythm in rectal temperature, as an index of fever, at 1 hr after IFN
      alpha (10 MIU/kg, i.v.) injection. The rhythmic pattern resembled overall the
      rhythm occurring in the nondrugged state. IFN-alpha increased rectal temperature
      during the light phase, but not during the dark phase. The fever induced by IFN
      alpha was blocked by indomethacin (10 mg/kg, i.p.) pretreatment. There was no
      significant difference of plasma IFN-alpha concentrations at 0.167, 0.5 and 1 hr
      after IFN-alpha injection. Therefore the dosing time dependent difference of
      fever induced by IFN-alpha may be caused via that of PGE2 level elevated by IFN
      alpha. The choice of the most appropriate time of day for drug administration may
      help to achieve rational chronotherapeutics of IFN-alpha.

PMID- 9275014
TI  - Growth suppression and induction of heat-shock protein-70 by 9-cis beta-carotene
      in cervical dysplasia-derived cells.
AB  - The aim of the present study was to determine to what extent 9-cis beta-carotene,
      one of the most abundant naturally-occurring cis-isomers of beta-carotene, can
      inhibit the growth of cervical dysplasia-derived cells in comparison with all
      trans beta-carotene. We found that 9-cis beta-carotene was dose-dependently more
      effective than all-trans beta-carotene. Both carotenes induced the intracellular
      accumulation of heat-shock protein-70 (HSP70), and the treated cells showed
      morphological changes indicative of apoptosis. The results of the present study
      strongly suggest that the induction of HSP70 by beta-carotene might be involved
      in beta-carotene-mediated suppression of the cell growth through apoptosis.

PMID- 9275016
TI  - Sensitization to locomotor effects of methylphenidate in the rat.
AB  - A computerized activity monitoring system was used to investigate whether
      repeated exposure to methylphenidate (MPD) could produce sensitization to its
      locomotor effects in the rat. Male Sprague-Dawley rats were housed in test cages
      and activity was recorded continuously for 16 days as follows: Baseline activity
      (Day 1-2), recording following saline injection (Day 3), MPD Challenge Doses-
      either 0.6, 2.5, or 10 mg/kg of MPD (Day 4); five days of a repeated dose of 2.5
      mg/kg (Day 5-9), five additional recording days of no treatment (Days 10-14), and
      MPD Re-Challenge (Day 15). Each group was re-challenged with the same doses as on
      day 4. Recording was resumed for an additional post-treatment day (Day 16). All
      injections were at 14:00. Horizontal activity, total distance, vertical activity,
      stereotypic activity, and number of stereotypic movements were recorded and
      analyzed. An augmented response (i.e., sensitization) was observed only to the
      lower MPD doses of 0.6 and 2.5 mg/kg. The sensitized response was more pronounced
      for forward ambulation than for rearing, with a complete lack of sensitization to
      the stereotypic effects of MPD.

PMID- 9275017
TI  - Energy metabolism in human melanoma cells under hypoxic and acidic conditions in
      vitro.
AB  - The response to treatment and the malignant progression of tumours are influenced
      by the ability of the tumour cells to withstand severe energy deprivation during
      prolonged exposure to hypoxia at normal or low extracellular pH (pHe). The
      objective of the present work was to demonstrate intertumour heterogeneity under
      conditions of microenvironment-induced energy deprivation and to investigate
      whether the heterogeneity can be attributed to differences in the capacity of the
      tumour cells to generate energy in an oxygen-deficient microenvironment. Cultures
      of four human melanoma cell lines (BEX-c, COX-c, SAX-c, WIX-c) were exposed to
      hypoxia in vitro at pHe 7.4, 7.0 or 6.6 for times up to 31 h by using the steel
      chamber method. High-performance liquid chromatography was used to assess
      adenylate energy charge as a function of exposure time. Cellular rates of glucose
      uptake and lactate release were determined by using standard enzymatic test kits.
      The adenylate energy charge decreased with time under hypoxia in all cell lines.
      The decrease was most pronounced shortly after the treatment had been initiated
      and then tapered off. BEX-c and SAX-c showed a significantly higher adenylate
      energy charge under hypoxic conditions than did COX-c and WIX-c whether the pHe
      was 7.4, 7.0 or 6.6, showing that tumours can differ in the ability to avoid
      energy deprivation during microenvironmental stress. There was no correlation
      between the adenylate energy charge and the rates of glucose uptake and lactate
      release. Intertumour heterogeneity in the ability to withstand energy deprivation
      in an oxygen-deficient microenvironment cannot therefore be attributed mainly to
      differences in the capacity of the tumour cells to generate energy by anaerobic
      metabolism. The data presented here suggest that the heterogeneity is rather
      caused by differences in the capacity of the tumour cells to reduce the rate of
      energy consumption when exposed to hypoxia.

PMID- 9275018
TI  - Effects of diethylamine/nitric oxide on blood perfusion and oxygenation in the
      R3230Ac mammary carcinoma.
AB  - The effects of intravenous diethylamine/nitric oxide (DEA/NO), a short-acting
      nitric oxide (NO) donor, on systemic haemodynamics, muscle and tumour blood flow
      (MBF and TBF) and tumour oxygenation were examined in rats bearing subcutaneous
      R3230Ac carcinoma in the leg. The effects of DEA/NO on the diameters of tumour
      feeding and normal arterioles were evaluated in window chambers with and without
      implanted tumours. DEA/NO reduced mean arterial pressure (MAP) when given at
      doses > or = 100 nmol kg(-1), with maximal suppression at 0.5-1 min followed by
      return to baseline within 20 min. DEA/NO did not affect MBF except at the highest
      doses (500 and 1000 nmol kg(-1)). In contrast, DEA/NO reduced TBF and constricted
      tumour arterioles at doses > or = 100 nmol kg(-1). Tumour arteriolar vasomotion
      occurred in more than half the animals during hypotension and with a
      significantly higher frequency than in normal granulating tissue at a dose of 500
      nmol kg(-1). Normal arterioles rapidly and significantly vasodilated for about 3
      min and then returned to baseline. The reductions in TBF and MAP were accompanied
      by synchronous reduction in tumour pO2. Our findings suggest that DEA/NO
      decreases TBF in two ways. In the window chamber model, vascular steal occurs as
      normal arterioles adjacent to tumour dilate more than tumour arterioles during
      the initial period of hypotension. In leg tumours, the predominant mechanism is
      attributable to reduced perfusion pressure induced by lowered MAP, which
      decreases flow to the tumour, probably because of relatively higher flow
      resistance. The vasoconstriction and vasomotion in tumour arterioles during
      DEA/NO-induced hypotension may reflect differences in regulatory metabolism of NO
      between neoplastic and normal arterioles. Thus, intravenous injection of a short
      acting NO donor, DEA/NO, decreases MAP and heart rate, leading to subsequent
      decreases in tumour blood flow and oxygenation.

PMID- 9275019
TI  - Enhancement of bioreductive drug toxicity in murine tumours by inhibition of the
      activity of nitric oxide synthase.
AB  - Nitro-L-arginine inhibits the production of nitric oxide and can thereby cause
      vasoconstriction in vivo. One consequence of this is that nitro-L-arginine can
      increase hypoxia in a range of transplantable and spontaneous murine solid
      tumours. Bioreductive drugs such as RB6145 are more active under hypoxic
      conditions, and the combination of RB6145 with nitro-L-arginine in vivo shows
      greater anti-tumour activity than either agent individually. In mice given nitro
      L-arginine at 10 mg kg(-1) i.p. up to 1 h before or after 300 mg kg(-1) i.p.
      RB6145, survival of KHT tumour cells was reduced by 3-4 logs when assessed by
      clonogenic assay 24 h after treatment. RB6145 or nitro-L-arginine alone caused no
      more than 20% cell kill. Similar effects were found in SCCVII tumours. The tumour
      response to the drug combination was tumour size dependent, with increased tumour
      cell sensitivity occurring when the tumour volume at the time of treatment was
      increased. Further, the response of KHT tumours to the combination of RB6145 and
      nitro-L-arginine was also dependent on the time interval between treatment and on
      when tumours were excised for determination of survival in vitro. The relative
      surviving fraction was about 0.3 for intervals less than 4 h but was reduced to
      0.01 at 12 h and 0.001 at 24 h. These results were supported by histological
      examination of tumours, when necrosis at 2 h after treatment was less than 5% but
      increased to greater than 90% at 24 h. RB6145-induced normal tissue damage, as
      measured by CFU-A survival, was not altered by combining with nitro-L-arginine.
      Hence, this drug combination may provide therapeutic benefit. It is likely that
      the substantial anti-tumour effects are due to enhancement of bioreductive
      toxicity through increased tumour hypoxia, although additional mechanism(s) may
      also contribute to the overall response.

PMID- 9275020
TI  - Murine P-glycoprotein on stromal vessels mediates multidrug resistance in
      intracerebral human glioma xenografts.
AB  - Human glioma usually shows intrinsic multidrug resistance because of the blood
      brain barrier (BBB), in which membrane-associated P-glycoprotein (P-gp), encoded
      by the human multidrug resistance gene MDR1, plays a role. We studied drug
      sensitivity to vincristine (VCR), doxorubicin (DOX) and nimustine (ACNU) in both
      intracerebrally and subcutaneously xenotransplanted human glioma. We examined the
      levels of MDR1 and murine mdr3 gene expression in the xenografts by reverse
      transcriptase polymerase chain reaction and the localization of P-gp by
      immunohistochemistry. Six of seven subcutaneously transplanted xenografts (scX)
      were sensitive to the above three drugs. In contrast, all three intracerebrally
      transplanted human glioma xenografts (icX) were resistant to P-gp-mediated drugs
      VCR and DOX, but were sensitive to the non-P-gp-mediated drug ACNU. Neither icX
      nor scX showed any MDR1 expression. Intracerebrally transplanted human glioma
      xenografts showed an increased level of murine mdr3 gene expression, whereas scX
      showed only faint expression. The localization of P-gp was limited to the stromal
      vessels in icX by immunohistochemistry, whereas scX expressed no P-gp. Our
      findings suggest that the P-gp expressed on the stromal vessels in icX is a major
      contributing factor to multidrug resistance in human glioma in vivo.

PMID- 9275021
TI  - Organ involvement and phenotypic adhesion profile of 5T2 and 5T33 myeloma cells
      in the C57BL/KaLwRij mouse.
AB  - The aim of this study was to evaluate the tissue infiltration and phenotypic
      adhesion profile of 5T2 multiple myeloma (MM) and 5T33 MM cells and to correlate
      it with that observed in human disease. For each line, 30 mice were intravenously
      inoculated with myeloma cells and at a clear-cut demonstrable serum paraprotein
      concentration; mice were sacrificed and a number of organs removed. The
      haematoxylin-eosin stainings on paraffin sections were complemented with
      immunohistochemistry using monoclonal antibodies developed against the specific
      MM idiotype. When analysed over time, 5T2 MM cells could be observed in bone
      marrow samples from week 9 after transfer of the cells. For the 5T33 MM, a
      simultaneous infiltration was observed in bone marrow, spleen and liver 2 weeks
      after inoculation. Osteolytic lesions consistently developed in the 5T2 MM, but
      this was not consistent for 5T33 MM. PCNA staining showed a higher proliferative
      index for the 5T33 MM cells. The expression of adhesion molecules was analysed by
      immunohistochemistry on cytosmears: both 5T2 MM and 5T33 MM cells were LFA-1,
      CD44, VLA-4 and VLA-5 positive. We conclude that both lines have a phenotypic
      adhesion profile analogous to that of human MM cells. As the 5T2 MM cells are
      less aggressive than the 5T33 MM cells, their organ distribution is more
      restricted to the bone marrow and osteolytic lesions are consistently present,
      the former cell line induces myeloma development similar to the human disease.

PMID- 9275022
TI  - Characterization of a BMS-181174-resistant human bladder cancer cell line.
AB  - This study was undertaken to elucidate the mechanism of cellular resistance to
      BMS-181174, a novel analogue of mitomycin C (MMC), in a human bladder cancer cell
      line. The BMS-181174-resistant variant (J82/BMS) was established by repeated
      continuous exposures of parental cells (J82) to increasing concentrations of BMS
      181174 (9-40 nM) over a period of about 17 months. A 2.6-fold higher
      concentration of BMS-181174 was required to kill 50% of J82/BMS cell line
      compared with J82. The J82/BMS cell line exhibited collateral sensitivity to 5
      fluorouracil (5-FU), but was significantly more cross-resistant to MMC,
      melphalan, taxol, doxorubicin and VP-16. NADPH cytochrome P450 reductase and DT
      diaphorase activities, which have been implicated in bioreductive activation of
      MMC, were significantly lower in the J82/BMS cell line than in J82. The
      cytotoxicity of BMS-181174, however, was not affected in either cell line by
      pretreatment with dicoumarol, which is an inhibitor of DT-diaphorase activity.
      These results argue against a role of DT-diaphorase in cellular bioactivation of
      BMS-181174, a conclusion consistent with that of Rockwell et al (Biochem
      Pharmacol, 50: 1239-1243, 1995). BMS-181174-induced DNA interstrand cross-link
      (DNA-ISC) frequency was markedly lower in J82/BMS cell line than in J82 at every
      drug concentration tested. The results of the present study suggest that cellular
      resistance to BMS-181174 in J82/BMS cell line may be due to reduced DNA-ISC
      formation. However, the mechanism of relatively lower BMS-181174 induced DNA-ISC
      formation in J82/BMS cell line than in parental cells remains to be clarified.

PMID- 9275023
TI  - Design and mechanism of action of a novel cytotoxic 1,2,3-triazene-containing
      heterocycle, 3,5-dimethyl-pyrido-1,2,3,5-tetrazepin-4-one (PYRZ), in the human
      epithelial ovarian cancer cell line NIH:OVCAR-3 in vitro.
AB  - The mechanism of action of the novel heterocycle 3,5-dimethyl-pyrido-1,2,3,5
      tetrazepin-4-one (PYRZ), structurally related to temozolomide, was studied in the
      human ovarian tumour cell line OVCAR-3. Our results showed that, despite its
      marked structural similarities to temozolomide, PYRZ presents properties that are
      atypical of 1,2,3-triazene-containing alkylating agents. In a Maxam-Gilbert DNA
      sequencing assay, PYRZ showed background levels of DNA alkylation, in contrast to
      temozolomide which strongly alkylated DNA preferentially at guanine residues. At
      high concentrations, PYRZ inhibited the synthesis of DNA, RNA and protein 3 h
      after treatment, in contrast to temozolomide which, in previous work, was found
      to preferentially inhibit DNA synthesis in OVCAR-3 cells. In cells exposed to
      PYRZ, alkaline sucrose density-gradient centrifugation showed a dose-dependent
      increase in DNA fragmentation only 12 and 24 h after treatment. PYRZ induced
      increasing accumulation of cells in late S and G2+M 6-24 h after treatment. This
      also contrasts with previous work that showed delayed cell cycle arrest induced
      by temozolomide in OVCAR-3 cells and in the murine leukaemia L1210 cells. Cell
      killing kinetics by PYRZ showed a series of sigmoidal dose-response curves with
      50-90% cell killing attained as early as 24 h after treatment in the 25-100
      microM dose range. (IC50 clonogenic assay 18 microM). The results suggest that
      the mechanism of cell killing by PYRZ may be different from that of its parent
      drug temozolomide, and other alkyl-triazene-containing molecules of the same
      class.

PMID- 9275024
TI  - DDP-induced cytotoxicity is not influenced by p53 in nine human ovarian cancer
      cell lines with different p53 status.
AB  - Nine human ovarian cancer cell lines that express wild-type (wt) or mutated (mut)
      p53 were used to evaluate the cytotoxicity induced by cisplatin (DDP). The
      concentrations inhibiting the growth by 50% (IC50) were calculated for each cell
      line, and no differences were found between cells expressing wt p53 and mut p53.
      Using, for each cell line, the DDP IC50, we found that these concentrations were
      able to induce an increase in p53 levels in all four wt-p53-expressing cell lines
      and in one out of five mut-p53-expressing cell lines. WAF1 and GADD45 mRNAs were
      also increased by DDP treatment, independently of the presence of a wt p53. Bax
      levels were only marginally affected by DDP, and this was observed in both wt-p53
      and mut-p53-expressing cells. DDP-induced apoptosis was evident 72 h after
      treatment, and the percentage of cells undergoing apoptosis was slightly higher
      for wt-p53-expressing cells. However, at doses near the IC50, the percentage of
      apoptotic cells was less than 20% in all the cell lines investigated. We conclude
      that the presence of wt p53 is not a determinant for the cytotoxicity induced by
      DDP in human ovarian cancer cell lines.

PMID- 9275025
TI  - Absence of p21 expression is associated with abnormal p53 in human breast
      carcinomas.
AB  - The p53 tumour-suppressor gene is important in the regulation of cell growth and
      apoptosis, and loss of functional wild-type activity may be associated with
      tumour formation and resistance to therapy. Differentiation of functionally
      normal wild-type protein from mutant or abnormal protein remains difficult using
      either immunohistochemical assays or mutational DNA sequencing. p21(WAF1/CIP1)
      (p21) is induced by wild type p53 and plays an important role in promoting cell
      cycle arrest. To test the hypothesis that p21 protein expression may act as a
      downstream marker of tumours from patients with locally advanced breast cancer
      before treatment with doxorubicin, pretreatment p53 status had been characterized
      in 63 tumours by p53 protein immunostaining and DNA mutational analysis. There
      was a significant association between immunostaining for p53 and the presence of
      p53 mutations (P = 0.01). Of 56 patients available for determination of p21, 31
      (55%) expressed p21 protein. Twenty-eight out of 31 patients (90%) positive for
      p21 had low negative p53 protein expression, whereas only 3 of 13 patients (23%)
      with high p53 expressed p21 (P = 0.009). No association was seen between p21
      protein expression and p53 mutations (P = 0.24). The combination of p53 and p21
      immunostaining results improved the specificity of the immunostaining but at a
      cost of significant reduction in sensitivity. Immunohistochemical assessment of
      p21 protein expression is inversely associated with abnormal p53 protein in human
      breast cancer. The detection of p21 protein expression in combination with p53
      protein expression did not improve the ability of immunohistochemistry (IHC) to
      differentiate between normal and mutant p53 protein.

PMID- 9275026
TI  - The prognostic significance of expression of the multidrug resistance-associated
      protein (MRP) in primary breast cancer.
AB  - In the present study, we determined the frequency and intensity of MRP protein
      expression by monoclonal antibody immunohistochemistry in a series of 259
      resected invasive primary breast carcinomas, and we evaluated MRP
      immunoreactivity in relation to patient and tumour characteristics, relapse-free
      (RFS) and overall survival (OS). The immunostaining was graded on a
      semiquantitative scale that ranged from (-) to ( ). Overall, 34% of the tumours
      were positive for anti-MRP antibody: 19% showed weak cytoplasmic staining (+),
      14% had clear cytoplasmic staining (++) and only 1% of the tumours had a strong
      cytoplasmic as well as membranous staining ( ). MRP expression was not related to
      patient's age, menopausal status, tumour size, differentiation grade, oestrogen
      and progesterone receptor level or lymph node involvement. In an exploratory
      univariate analysis of all patients, only primary tumour size and number of lymph
      nodes involved were significantly associated with shortened RFS (P < 0.001 and P
      < 0.001 respectively) and OS (P = 0.02 and P < 0.001 respectively). In Cox
      univariate analysis for RFS in subgroups of patients stratified by menopausal
      status, tumour size, nodal status, adjuvant systemic therapy and oestrogen and
      progesterone receptor status, MRP expression was associated with increased risk
      for failure in patients with small tumours (T1), in node-negative patients and in
      node-positive patients who received adjuvant systemic chemotherapy with
      cyclophosphamide, methotrexate and 5-fluorouracil (CMF); the relative hazard rate
      (RHR) for relapse was increased in the presence of MRP, with RHR values with 95%
      confidence limits (CL) of 2.8 (1.2-6.9), 2.1 (1.0-4.2) and 2.8 (0.8-9.9)
      respectively. In analysis for OS, expression of MRP was also associated with
      increased risk for failure in patients with small tumours (T1) [RHR (95% CL) 2.3
      (0.9-6.0)] and in node-positive patients who received adjuvant systemic
      chemotherapy with CMF [RHR (95% CL) 3.7 (0.8-17.1)] but not in node-negative
      patients [RHR (95% CL) 1.1 (0.4-2.6)]. In conclusion, our results show that MRP
      is frequently overexpressed in primary breast cancer and suggest that MRP
      expression might be of prognostic significance in the subgroups of patients with
      the more favourable prognosis, i.e. patients with small tumours and node-negative
      patients, as well as in the setting of adjuvant systemic chemotherapy. In primary
      breast cancer, MRP might be related to altered cell biological behaviour,
      including a more aggressive phenotype, and resistance to adjuvant systemic
      chemotherapy.

PMID- 9275027
TI  - Nipple aspirate fluid: a promising non-invasive method to identify cellular
      markers of breast cancer risk.
AB  - To evaluate the feasibility of nipple aspiration and to identify intermediate
      markers of breast cancer risk, nipple aspirate fluid (NAF) was collected from 177
      subjects using a modified breast pump. The first 33 subjects demonstrated that we
      could obtain NAF quickly, reliably and repeatedly. Specimens from the remaining
      144 subjects were collected to evaluate promising cellular biomarkers. NAF was
      obtained in 167 out of 177 (94%) subjects overall and in 99% of the 144 most
      recent subjects. Sufficient NAF was obtained to evaluate cytology in 160 out of
      167 (96%) cases and specimens were sufficiently cellular to analyse DNA markers
      in 53% of cases. Among the last 144 subjects, menopausal status did not influence
      the ability to obtain NAF. NAF cytology correlated with increased breast cancer
      risk (P = 0.002). Using computerized image analysis of NAF epithelial cells, DNA
      index (P = 0.0002), percentage of cells in G2M (P = 0.05) and percentage of cells
      with hypertetraploidy (P = 0.002) increased as cytology became more abnormal. Our
      data indicate that NAF can be obtained in essentially all eligible subjects; that
      breast epithelial cells are evaluable in > 95% of NAF samples for cytology and in
      over half of NAF samples for DNA index (ploidy) and cell cycle analysis; and that
      abnormal NAF cytology correlates with increased breast cancer risk. This suggests
      that biomarkers identified in nipple aspirate fluid may prove useful either as an
      adjunct to currently accepted breast cancer screening methods, or to evaluate
      response to a chemopreventive agent.

PMID- 9275028
TI  - Stereoselective peripheral sensory neurotoxicity of diaminocyclohexane platinum
      enantiomers related to ormaplatin and oxaliplatin.
AB  - The diaminocyclohexane platinum (Pt(DACH)) derivatives ormaplatin and oxaliplatin
      have caused severe and dose-limiting peripheral sensory neurotoxicity in a
      clinical trial. We hypothesized that this toxicity could vary in relation to the
      biotransformation and stereochemistry of these Pt(DACH) derivatives. We prepared
      pure R,R and S,S enantiomers of ormaplatin (Pt(DACH)Cl4), oxaliplatin
      (Pt(DACH)oxalato) and their metabolites (Pt(DACH)Cl2 and Pt(DACH)methionine) and
      assessed their peripheral sensory neurotoxicity and tissue distribution in the
      rat and in vitro anti-tumour activity in human ovarian carcinoma cell lines. The
      R,R enantiomers of Pt(DACH)Cl4, Pt(DACH)oxalato and Pt(DACH)Cl2, induced
      peripheral sensory neurotoxicity at significantly lower cumulative doses (18 +/-
      5.7 vs 32 +/- 2.3 micromol kg(-1); P < 0.01) and at earlier times (4 +/- 1 vs 6.7
      +/- 0.6 weeks; P = 0.016) during repeat-dose treatment than the S,S enantiomers.
      Pt(DACH)methionine enantiomers showed no biological activity. There was no
      difference between Pt(DACH) enantiomers in the platinum concentration in sciatic
      nerve, dorsal root ganglia, spinal cord, brain or blood at the end of each
      experiment. Three human ovarian carcinoma cell lines (41 M, 41 McisR and SKOV-3)
      showed no (or inconsistent) chiral discrimination in their sensitivity to
      Pt(DACH) enantiomers, whereas two cell lines (CH-1 and CH-1cisR) showed modest
      enantiomeric selectivity favouring the R,R isomer (more active). In conclusion,
      Pt(DACH) derivatives exhibit enantiomeric-selective peripheral sensory
      neurotoxicity during repeated dosing in rats favouring S,S isomers (less
      neurotoxic). They exhibited less chiral discrimination in their accumulation
      within peripheral nerves and in vitro anti-tumour activity.

PMID- 9275029
TI  - Ex vivo cytotoxic drug evaluation by DiSC assay to expedite identification of
      clinical targets: results with 8-chloro-cAMP.
AB  - There is a pressing need to reduce the time and cost of developing new cytotoxic
      agents and to accurately identify clinically active agents at an early stage. In
      this study, the differential staining cytotoxicity (DiSC) assay was used to
      assess the efficacy of the novel antitumour cAMP analogue, 8-chloro-cAMP (8-Cl
      cAMP) (and its metabolite 8-Cl-adenosine) against 107 fresh specimens of human
      neoplastic and normal cells. Diagnoses included chronic and acute leukaemias,
      myeloma, non-Hodgkin's lymphoma (NHL) and miscellaneous solid tumours. The aim
      was to identify targets for subsequent phase I, II and III trials. 8-Cl-cAMP was
      tested at 4-985 microM, along with standard chemotherapeutic drugs. 8-Cl-cAMP and
      its metabolite caused no morphologically observable cell differentiation but
      induced dose-dependent cytotoxicity. Compared with untreated patients, previously
      treated chronic lymphocytic leukaemia (CLL) patients showed no increase in ex
      vivo resistance to 8-Cl-cAMP (P = 0.878); minimal cross-resistance with other
      cytotoxic drugs was detected. Compared with normal cells (mean LC90 = 1803
      microM), 8-Cl-cAMP showed significant ex vivo activity against CLL (117.0 microM;
      P < 0.0001) and NHL (140.0 microM; P < 0.0001), of which eight were mantle cell
      NHL (84.7 microM), and greatest activity against cells from patients with acute
      myeloid leukaemia (AML; mean LC90 = 24.3 microM; in vitro therapeutic index 74
      fold, P < 0.0001). Solid tumour specimens were comparatively resistant to 8-Cl
      cAMP. The results highlight the clinical potential of 8-Cl-cAMP, point to several
      new phase I, II and III trial possibilities and provide a rationale for the
      inclusion of ex vivo cytotoxic drug evaluation in the drug development process.

PMID- 9275030
TI  - Comparison of a new microplate oestrogen receptor (ER) enzyme immunoassay with
      other ER detection methods.
AB  - In a study involving 50 breast cancer tumours, we compared two oestrogen receptor
      (ER) detection methods developed by us--a microplate immunoenzymometric assay
      (EIA96) and an immunohistochemistry kit (HistoCIS-ER)--with the radioligand assay
      (RLA), the Abbott immunoenzymometric assay ER-EIA and the reverse transcriptase
      polymerase chain reaction technique (RT-PCR). Among the three ER protein
      cytosolic assays (EIA96, ER-EIA and RLA), the two EIAs showed the best agreement
      (y = 1.086x - 7.840; r2 = 0.876). At the calculated optimal cut-off values (8 and
      14 fmol mg(-1) protein for EIA96 and RLA respectively), EIA96 was more sensitive
      than RLA (0.94 for EIA96, 0.88 for RLA), but slightly less specific (0.82 for
      EIA96, 0.94 for RLA). The Cox logistical regression model applied to EIA96, RLA
      and RT-PCR showed that EIA96 discriminated the best between ER-EIA+ and ER-EIA-
      samples. The RT-PCR technique and HistoCIS-ER both had a positivity-negativity
      concordance of 86% with EIA96.

PMID- 9275032
TI  - Clinical significance of tissue inhibitor of metalloproteinase expression in
      gastric carcinoma.
AB  - Tissue inhibitor of metalloproteinase (TIMP) has been reported to inhibit tumour
      invasion through an inactivation of matrix metalloproteinase (MMP) both in vitro
      and in vivo. Among the TIMP family, TIMP-1 possesses not only proteinase
      inhibitory activity but also a growth-promoting function. However, the
      significance of the expression of TIMP-1 in human gastric carcinoma tissue has
      yet to be clarified. In 50 examined cases of gastric carcinoma, 44 (88%) cases
      showed a higher expression of TIMP-1 mRNA in the biopsy samples from the tumour
      tissue (T) than in the biopsy samples from the corresponding normal tissue (N),
      as determined by semiquantitative reverse transcriptase-polymerase chain reaction
      (RT-PCR). In a multivariate analysis, the T/N ratio of TIMP-1 mRNA was found to
      be an independent factor influencing the depth of tumour invasion and was the
      second most important factor in determining the prognosis of patients. As RT-PCR
      assay can be performed on biopsy specimens obtained before surgery, an evaluation
      of the TIMP-1 expression in biopsy specimens by RT-PCR may thus provide useful
      preoperative information on tumour aggressiveness.

PMID- 9275031
TI  - Stromal tenascin distribution as a prognostic marker in colorectal cancer.
AB  - A total of 169 colorectal adenocarcinomas, obtained from patients with a median
      follow-up of 6.5 years, were studied with immunohistochemical staining on
      cryosections using a monoclonal anti-tenascin antibody to evaluate the possible
      association between the staining patterns and tumour stage, tumour
      differentiation and survival. We found two different staining patterns in the
      tumour stroma--a diffuse stromal fibrillar staining in 92 out of 169 (54%)
      tumours and a subglandular staining in the remaining 77 tumours. When the entire
      group of patients (P < 0.01) and the group of potentially cured patients (P <
      0.03) were analysed univariately, it was found that diffuse stromal fibrillar
      staining was associated with a shorter survival time than subglandular staining.
      In a multivariate analysis, the Dukes' stage and age were independent prognostic
      factors, whereas the tenascin expression did not retain a clear independent
      relationship to survival (P = 0.06). Hence, it appears that the tumour expression
      of tenascin may be a potential prognostic marker in colorectal cancer, in so far
      as a diffuse stromal fibrillar staining pattern seems to indicate an increased
      risk of poor outcome. However, after adjustment for age and Dukes' stage, the
      additional prognostic value of tenascin remains to be established in further
      analyses.

PMID- 9275033
TI  - Plasminogen activator inhibitor-1 (PAI-1) is not related to response to
      neoadjuvant chemotherapy in breast cancer.
AB  - There is no information available on the relation between response to
      chemotherapy and the high-risk phenotype assessed by uPA and/or PAI-1. The
      clinical situation of neoadjuvant chemotherapy provides a means of rapidly
      assessing the sensitivity of the primary tumour to cytotoxic drug regimens. The
      goal of the study was to assess prospectively the predictive value of PAI-1 for
      response to first-line chemotherapy. PAI-1 concentration was measured on
      hypertonic cytosolic extracts (0.4 M potassium chloride) by ELISA before
      chemotherapy on a drill biopsy sample of the tumour in 69 T2 and T3 breast cancer
      patients (median age 46 years). Oestrogen receptor (ER) (51% ER+), progesterone
      receptor (PR) (58% PR+), S-phase (median 4.0%) and ploidy were also assessed in
      the majority of cases. The clinical response to treatment was evaluated after
      four cycles of FAC or FEC regimen (5-fluorouracil, epidoxorubicin or doxorubicin
      and cyclophosphamide) (one cycle every 4th week). PAI-1 could be assayed in 29
      post-chemotherapy surgical samples. The objective response rate (complete
      response plus partial response) was 59% (41 out of 69). PAI-1 expressed as gram
      of tissue (range 19-2370 ng g(-1) tissue) was highly correlated (r = 0.98) to PAI
      1 expressed as mg protein (range 0.5-68 ng mg(-1) protein). No correlation
      between PAI-1 level and response could be observed, with any cut-off. The post-
      and pre-chemotherapy PAI-1 levels were correlated (r = 0.66). Of all biological
      parameters, only high S-phase (cut-off 5%) was slightly correlated (chi2 = 3.91,
      P = 0.05) to response. These data suggest that PAI-1 is not a predictive marker
      of response to chemotherapy in breast cancer and that its level is not altered by
      neoadjuvant chemotherapy.

PMID- 9275034
TI  - Effectiveness of very low doses of immunotherapy in advanced renal cell cancer.
AB  - Twenty-one nephrectomized patients with metastatic renal cell cancer were treated
      with recombinant interleukin 2 (rlL-2) and interferon alpha (rIFN alpha). rIL-2
      was administered s.c. at a dose of 1 x 10(6) IU m(-2) every 12 h on days 1 and 2,
      followed by 0.5 x 10(6) IU twice daily on days 3-5; rIFN alpha-2 was given i.m.
      as 1.8 x 10(6) IU m(-2) on days 3 and 5 of each week for 4 consecutive weeks. The
      cycle was regularly repeated at 4-month intervals and continued ad libitum in
      patients showing some response and in patients with progressing disease. Of 20
      patients evaluable for treatment response, one (5%) had a complete response and
      three (15%) showed partial response. Three patients (15%) achieved stable disease
      and 13 (65%) were evaluated as having progressive disease. The estimated
      actuarial 44-month survival rate was 44%. Toxicity was limited to WHO grades 1
      and 2 only.

PMID- 9275035
TI  - Less efficacy with alternating regimen as adjuvant chemotherapy in stage II node
      positive breast cancer: results at 8 years (Pronacam 85).
AB  - A randomized trial to compare adjuvant treatment with an alternating regimen with
      conventional chemotherapy was performed. A total of 589 node-positive patients
      were included and stratified according to number of positive nodes (N1-3 and N >
      4) and menopausal status. Premenopausal N1-3 patients were randomized to
      cyclophosphamide, methotrexate and fluorouracil (CMF) or CMF/4'-epirubicin,
      cyclophosphamide (EC), post-menopausal N1-3 patients to fluorouracil, 4
      epirubicin, cyclophosphamide (FEC) or CMF/EC and pre- and post-menopausal
      patients with N > or = 4 to fluorouracil, 4' epirubicin, cyclophosphamide,
      methotrexate, prednisone (FECMP) or CMF/EC. In premenopausal patients, CMF was
      superior to CMF/EC in terms of disease-free survival (DFS) (65% vs 45%, P =
      0.0149) and survival (72.3% vs 50.2%, P = 0.0220) whereas, for N > or = 4
      patients, differences between FECMP and CMF/EC did not achieve statistical
      significance (DFS 35% vs 26.2%; survival 50% vs 38.1%, P = NS). For post
      menopausal patients, FEC was superior to CMF/EC in DFS (58.6% vs 36.8%, P =
      0.0215) and survival (66.2% vs 46%, P = 0.0155). In post-menopausal patients with
      N > 4, differences favouring CMF/EC were significant in DFS (40.4% vs 22%, P =
      0.0371) but not in survival (47.4% vs 32.2%, P = 0.1185). Alternating regimens
      did not offer better results in premenopausal and post-menopausal N1-3 patients.
      Results regarding post-menopausal N > 4 women require further confirmation.

PMID- 9275037
TI  - Growth without a pituitary?--Lessons from the guinea pig.

PMID- 9275036
TI  - Cautionary tales of survival analysis: conflicting analyses from a clinical trial
      in breast cancer.
AB  - Data from a completed randomized trial in breast cancer are used to demonstrate
      and quantify the variation in estimated survival curves and log-rank statistics
      at different times throughout a trial. False 'plateaux' are common, as are wide
      fluctuations in chi2 values obtained from the log-rank test when there are few
      events. We show how analyses conducted at different times can demonstrate
      different effects. Long follow-up is often necessary to allow correct
      interpretation of results. We discuss the assumption of proportional hazards and
      the consequences of making that assumption inappropriately. We show how checking
      whether hazards are proportional can help in avoiding erroneous conclusions.

PMID- 9275038
TI  - Guinea pig serum contains a specific high affinity growth hormone-binding protein
      with novel ligand specificity.
AB  - Previous workers have suggested that guinea pig serum does not contain a GH
      binding protein (GHBP) or that it is defective. The current studies, however,
      have identified and characterized the presence of GH-binding activity in guinea
      pig serum using gel chromatography to separate bound and free hormone. The
      detection of GH-binding activity is critically reliant on the type of radioligand
      used to measure binding. Clear identification of GH-binding activity was
      demonstrated with [125I]ovine GH (oGH), but specific binding could not be
      measured with [125I]human GH. The novel specificity was also shared by guinea pig
      liver membrane GH receptor (GHR) and cytosol GHBP, suggesting structural
      similarity in the GH-binding domain between the GHR and soluble GHBPs. The
      binding of oGH was dependent on serum concentration (5 microl serum produced
      16.03 +/- 0.5% specific binding; mean +/- SEM; n = 11) and incubation time
      (equilibrium was reached by approximately 6 h at 21 C) and was completely
      reversible (t(1/2), approximately 2 h). Scatchard analysis revealed linear plots
      with an affinity constant (Ka) of 0.59 +/- 0.09 x 10(9) M(-1) and a capacity of
      23,181 +/- 4,474 fmol/ml serum. Similar association constants were obtained for
      liver membrane GHR (0.79 +/- 0.22 x 10(9) M(-1)) and cytosol GHBPs (0.99 +/- 0.15
      x 10(9) M(-1)), but the capacity, when expressed as femtomoles per g tissue, was
      significantly increased (4-fold) in cytosol (4,303 +/- 505) over that in
      membranes (1,071 +/- 257). There was no sex difference in Ka or level of GHBP in
      guinea pig serum. Surprisingly, the level of GH-binding activity was very low to
      undetectable in pregnant guinea pig serum. Characterization of the native
      structure of guinea pig GHBPs has indicated the presence of several proteins that
      are structurally distinct. Although the distribution of GH-binding activity
      covered a large Mr range (approximately 70-350 kDa) the major form of the
      circulating GHBP identified by gel chromatography had an apparent native Mr of
      150-170 kDa. Partially purified GHBP (approximate Mr, 170 kDa) was covalently
      cross-linked to [125I]oGH and subjected to nonreducing SDS-PAGE. Specific GHBP
      complexes of 158 and 85 kDa were detected, suggesting that the partially purified
      GHBP complex may be composed of a smaller GHBP associated noncovalently with a
      non-GH-binding protein. "Pore limit" native PAGE (cathodic and anodic) revealed
      the presence of specific GHBPs of 363, 158, 74, and 55 kDa, which cross
      hybridized with the rat liver membrane GHR monoclonal antibody mAb 263 but not
      with the rat serum GHBP-specific mAb 4.3. Interestingly, although GH binding was
      undetectable in pregnant guinea pig serum, Western immunoblot analysis with mAb
      263 demonstrated the presence of a major immunoreactive GHBP band of 105 kDa in
      addition to 158- and 55-kDa GHBPs. The data indicate that the GHBPs are
      immunologically related to the rat membrane GHR, but provide no evidence to
      support the presence of a hydrophilic tail sequence homologous to that in the rat
      GHBP. These studies have identified in guinea pig serum GHBPs that exhibit novel
      ligand specificity, structural heterogeneity, and an immunological relationship
      to the rat liver membrane GHR. The identification of serum GHBP and the novel
      ligand specificity, which is also expressed by the liver membrane GHR, argue
      against the view that the guinea pig has a defective GHBP.

PMID- 9275039
TI  - Regulation of the adenohypophyseal thyrotropin-releasing hormone-degrading
      ectoenzyme by estradiol.
AB  - TRH is inactivated by the TRH-degrading ectoenzyme, a TRH-specific
      metallopeptidase. At the pituitary level, this enzyme is stringently regulated by
      thyroid hormones. We describe here gender-related differences and the effect of
      estradiol (E2) on the expression of this enzyme in the anterior pituitary.
      Compared with male rats, only about one third of the enzymatic activities and the
      messenger RNA levels were found in the anterior pituitary of female rats, whereas
      the TRH receptor transcript levels were found inversely related. When male rats
      received a single injection of 0.5 microg E2/100 g BW, the enzymatic activity
      decreased to 65% of control values within 14 h, preceded by a decrease of the
      transcript levels to 25% of control within 6 h. Basal values were reached again
      24-48 h after the injection. E2 had no effect on the expression of the enzyme in
      the brain. In vivo and with GH3 cells in vitro, E2 effectively counteracted the
      increase in enzymatic activity induced by T3, whereas neither testosterone nor
      progesterone, aldosterone, or dexamethasone showed any significant effects.
      Because the expression of the adenohypophyseal TRH-degrading ectoenzyme is
      tightly regulated by both T3 and E2 with adequate dynamics, we conclude that this
      peptidase serves integrative functions for the control of TRH-stimulated hormone
      secretion.

PMID- 9275040
TI  - Parathyroid hormone increases prostaglandin G/H synthase-2 transcription by a
      cyclic adenosine 3',5'-monophosphate-mediated pathway in murine osteoblastic
      MC3T3-E1 cells.
AB  - PTH increased PG synthase-2 transcription in osteoblastic MC3T3-E1 cells at 30
      min, as assessed by nuclear run-on assays. To determine the signaling pathways
      used by PTH, the activity of a construct containing the PG synthase-2 gene
      between nucleotides -963 and +70 linked to a luciferase reporter was analyzed in
      stably transfected MC3T3-E1 cells. Agents that activate the cAMP-protein kinase A
      or protein kinase C pathways increased PG synthase-2 promoter activity. In
      contrast, the calcium ionophore ionomycin was ineffective. The protein kinase A
      inhibitor H89 blocked PTH stimulation of PG synthase-2 promoter activity, whereas
      an overnight pre-incubation with phorbol ester to down-regulate protein kinase C
      did not. PTH-(3-34), a peptide that has greatly reduced ability to activate the
      cAMP-protein kinase A pathway, did not increase PG synthase-2 transcription or
      promoter activity. PTH could induce PG synthase-2 messenger RNA accumulation and
      PG synthase-2 transcription in the presence of cycloheximide. In addition, PTH
      stimulated PG synthase-2 transcription was maintained at a high level at 2 h in
      the presence of cycloheximide. We conclude that PTH rapidly increases PG synthase
      2 transcription in MC3T3-E1 cells, mainly through a cAMP-protein kinase A
      mediated pathway without the need for protein synthesis. In contrast, the
      attenuation of increased PG synthase-2 transcription by PTH requires de novo
      protein synthesis.

PMID- 9275041
TI  - Stimulation of cell proliferation by calcium and a calcimimetic compound.
AB  - Some mesenchymal cells respond to stimulation by specific cations with increased
      cell proliferation. In the present study we have investigated whether the
      parathyroid/kidney/brain calcium-sensing receptor (PCaR) can mediate such
      mitogenic responses. We have expressed the recombinant rat PCaR in CCL39 hamster
      fibroblasts, which do not express a detectable endogenous cation sensor. The
      transfected cells responded to increased extracellular calcium concentrations
      ([Ca2+]e) with strong inositol phosphate (IP) formation, which was insensitive to
      pertussis toxin treatment of cells. We could not detect negative coupling of the
      receptor to adenylyl cyclase. The calcimimetic NPS R-568 left-shifted the
      concentration-response curve for [Ca2+]e-induced IP formation and increased the
      maximal response. In [3H]thymidine incorporation experiments, increasing [Ca2+]e
      from 1 to 4 mM was found to stimulate DNA synthesis weakly, but significantly. A
      strong potentiation of this response was observed in the presence of NPS R-568.
      [Ca2+]e and NPS R-568 also synergized to increase cell numbers in cultures
      maintained in defined medium. In contrast to our expectations, no significant
      stimulation of IP formation or cell proliferation could be observed after
      stimulation of cells with the reported PCaR agonist gadolinium (Gd3+) or with
      aluminum (Al3+), which stimulates osteoblast proliferation. Gd3+ actually
      inhibited IP formation stimulated by increased [Ca2+]e as well as by thrombin and
      AlF4-, indicating toxicity. However, submaximal receptor stimulation by Gd3+ was
      evident when intracellular calcium transients were measured in fluo-3-loaded
      cells. Our data show that PCaR can stimulate cell proliferation when expressed in
      an appropriate cellular context. However, it is unlikely that PCaR mediates the
      strong mitogenic effects elicited by the cations Gd3+ and Al3+ observed in
      osteoblasts.

PMID- 9275042
TI  - Ascorbic acid alters collagen integrins in bone culture.
AB  - The effects of ascorbic acid on collagen synthesis, mineralization, and integrins
      were investigated in a mineralizing organ culture system derived from 20-day
      fetal rat parietal bones. A significant dose-dependent decrease in calcification
      at 96 h was demonstrated with decreasing concentrations of ascorbic acid (100-0
      microg/ml). No effect on DNA content, [3H]thymidine incorporation, or dry weight
      was found in control (100 microg/ml ascorbic acid) bones compared with bones
      treated with decreased ascorbic acid concentrations (10, 1, and 0 microg/ml).
      Collagen synthesis, measured by [3H]proline incorporation, and alpha1(I)
      procollagen messenger RNA levels were also unaffected. However, ascorbic acid
      produced a dose-dependent decrease in the hydroxyproline content, with a maximal
      76.8% decrease in bones without ascorbic acid compared with the control bones
      with 100 microg/ml ascorbic acid. Light microscopy of the ascorbic acid-deficient
      bones revealed a disruption of the osteoblast layer with misshapen osteoblasts
      and a decrease in the osteoid seam. The loss of osteoblast organization was also
      confirmed by analyzing the integrins for collagen by Northern and Western blot
      and immunofluorescence microscopy. A dose-dependent decrease in alpha2 and beta1
      integrin messenger RNA levels and in alpha1, alpha2, and beta1 protein were found
      in 96-h bone cultures deficient in ascorbic acid. These integrin subunits mediate
      the binding of osteoblasts to collagen. Immunofluorescence microscopy also
      demonstrated a dose-dependent decrease in alpha2 and beta1 staining of the
      osteoblast layer. However, the protein levels of alpha3 and alpha5 subunits were
      not affected. No beta5 was detected, whereas only bones cultured without ascorbic
      acid demonstrated a small decrease in alpha(v) and beta3 protein levels. The
      alpha3, alpha5, alpha(v), and beta3 subunits are involved in cell binding to
      extracellular matrix proteins other than collagen. Thus, the integrins for
      collagen are down-regulated, probably in response to the underhydroxylated
      collagen fibrils, which causes a disruption of osteoblast organization leading to
      a decrease in mineralization of bone. Integrin assays for specific extracellular
      proteins may be useful tools in detecting matrix defects in various metabolic
      bone diseases.

PMID- 9275043
TI  - Insulin-like growth factor I in the teleost Oreochromis mossambicus, the tilapia:
      gene sequence, tissue expression, and cellular localization.
AB  - Using reverse transcription-PCR and molecular cloning, the complementary DNA
      sequence encoding preproinsulin-like growth factor I (IGF-I) of a teleost, the
      tilapia (Oreochromis mossambicus) was established from liver. At the amino acid
      level, tilapia IGF-I shows all residues necessary for the maintenance of tertiary
      structure and shares about 80% identity with IGF-I from other teleosts. The B and
      A domains of tilapia IGF-I show more than 90% homology to those of other teleosts
      and 86-93% to those of human. However, in contrast to salmonids, the C domain of
      tilapia is truncated. Reverse transcription-PCR analysis followed by Southern
      blotting with an internal probe specific for tilapia IGF-I indicated a transcript
      in liver, pancreas, gut, kidney, head kidney, gill, ovary, testis, eye, and
      brain. In correlation, parenchymal cells were identified as likely local
      production sites by the use of immunohistochemistry. IGF-I immunoreactivity was
      confined to D cells in pancreatic islets, gastroentero-endocrine cells, cells of
      renal proximal tubules, interrenal cells of the head kidney, gill chondrocytes,
      chloride cells of the gill epithelium, granulosa cells in the ovary,
      spermatocytes and Sertoli cells in testis, and neurons in retina and brain. The
      local production of IGF-I in multiple organs of the tilapia indicates
      paracrine/autocrine actions of IGF-I involved in organ-specific functions. The
      results further demonstrate that the primary structure of IGF-I, especially in
      the B and A domains, is highly conserved during phylogeny.

PMID- 9275044
TI  - Prohormone convertase 2 is necessary for the formation of cholecystokinin-22, but
      not cholecystokinin-8, in RIN5F and STC-1 cells.
AB  - Two endocrine tumor cell lines from pancreas (RIN5F) and intestine (STC-1)
      express cholecystokinin (CCK) messenger RNA and are able to posttranslationally
      process pro-CCK to CCK-22 and CCK-8 amide. Both of these forms are also secreted
      by these cells. Because they make and secrete forms of amidated CCK larger than
      CCK-8, they represent a model of pro-CCK processing in the gut and allow
      investigation of possible mechanisms for tissue differences in prohormone
      processing. Both of these cells express two endoproteases convertase-1 (PC1) also
      known as PC3 and prohormone convertase-2 (PC2), which may be involved in pro-CCK
      processing. We have previously shown than inhibition of PC1 expression in these
      cells using stable expression of antisense messenger RNA caused a significant
      reduction in cellular content of amidated CCK and caused a selective depletion of
      CCK-8 with a comparative sparing of CCK-22. We demonstrate here that inhibition
      of PC2 expression in these cells also caused a large initial decrease in CCK
      content and produced a selective depletion of CCK-22 and a comparative sparing of
      CCK-8. These results support both a role for both PC1 and PC2 in pro-CCK
      processing in these cells and the hypothesis that tissue-specific processing of
      pro-CCK may be explained by differences in expression or activity of PC1 and PC2.

PMID- 9275045
TI  - Thyrotropin regulation by thyroid hormone in thyroid hormone receptor beta
      deficient mice.
AB  - Thyroid hormone responsive genes can be both positively and negatively regulated
      by thyroid hormone. TSH is down-regulated by thyroid hormone and rises during
      thyroid hormone deprivation. Because both thyroid hormone receptor (TR) alpha and
      beta genes are expressed in the pituitary gland, it is unclear what the relative
      roles of TR alpha and TR beta are in TSH regulation. Experiments using over
      expression of artificial genes have yielded conflicting results. The TR beta
      knock-out mouse that lacks both TR beta1 and TR beta2 isoforms provides a model
      to examine the role of these receptors in TSH regulation. TR beta deficient (TR
      beta-/-) and wild-type (TR beta+/+) mice of the same strain were deprived of
      thyroid hormone by feeding them a low iodine diet containing propylthiouracil and
      were then treated with different doses of L-T3 and L-T4. Thyroid hormone
      deprivation rapidly increased the serum TSH level in both TR beta+/+ and TR beta
      /- mice, reaching a similar level in the absence of thyroid hormone. In contrast,
      the decline of serum TSH by treatment with both L-T3 and L-T4 was severely
      blunted in TR beta-/- mice, and full suppression was not achieved with the
      maximal L-T3 dose of 25 microg/day x mouse. These data indicate that TR beta is
      not required for the up-regulation of TSH in thyroid hormone deficiency. However,
      although TR alpha alone can mediate thyroid hormone induced TSH suppression, TR
      beta enhances the sensitivity of TSH down-regulation and may be essential for the
      complete suppression of TSH.

PMID- 9275046
TI  - Effects of nitric oxide on ovulation and ovarian steroidogenesis and
      prostaglandin production in the rabbit.
AB  - Evidence supports the involvement of nitric oxide (NO) in ovarian physiology. The
      present study was undertaken to investigate the role of the NO/NO synthase (NOS)
      systems in ovulation, oocyte maturation, ovarian steroidogenesis, and PG
      production using in vitro perfused rabbit ovaries. The addition of the NOS
      inhibitors, aminoguanidine hemisulfate salt (AG) and N-omega-nitro-L-arginine
      methyl ester (L-NAME), to the perfusate inhibited the ovulation induced by hCG in
      a dose-dependent manner, whereas D-NAME had no significant effect. Neither AG nor
      L-NAME affected the hCG-induced meiotic maturation of the ovulated ova. The
      exogenous administration of the NO generator, sodium nitroprusside (NP), induced
      follicle rupture in the absence of gonadotropin, but did not induce oocyte
      maturation. Inhibition of endogenous NOS by AG and L-NAME resulted in a
      significant elevation in the production of estradiol (E2), but not of
      progesterone, stimulated by hCG. The concomitant administration of NP
      significantly reduced the AG-stimulated production of E2 by ovaries perfused in
      the presence of hCG, which suggests that NO down-regulates ovarian E2 synthesis.
      Ovarian production of PGE2 and PGF2alpha in response to hCG was significantly
      blocked by L-NAME, and exogenous administration of NP stimulated the production
      of PGs in the absence of gonadotropin. Significant correlations were observed
      between the ovulatory efficiencies and the production of PGs by rabbit ovaries
      perfused with or without L-NAME. In conclusion, the ovarian NO/NOS system is
      involved in follicle rupture during the ovulatory process. NO may induce follicle
      rupture in rabbit ovaries at least in part by the stimulation of PG production.

PMID- 9275047
TI  - Induction of cyclooxygenase-2 and prostaglandin F2alpha receptor expression by
      interleukin-1beta in cultured human granulosa-luteal cells.
AB  - Prostanoids are important regulators of ovarian function, especially during
      ovulation and luteolysis. Cyclooxygenase (Cox) is the rate-limiting enzyme in
      conversion of arachidonic acid to prostanoids. We have examined the expression
      and regulation of the inducible Cox isoform (Cox-2) and of the receptor for
      PGF2alpha (FP) in human granulosa cells obtained from women undergoing oocyte
      retrieval for in vitro fertilization. Freshly isolated granulosa cells express
      Cox-2 and FP receptor messenger RNAs (mRNAs). FP receptor mRNA is also expressed
      in cultured human granulosa-luteal (GL) cells, but Cox-2 transcripts are
      expressed only upon induction. Interleukin-1beta (IL-1beta) elevated Cox-2 mRNA
      steady state levels in a concentration-dependent manner, and kinetic studies
      showed that Cox-2 mRNA levels were already induced at the 2 h point and returned
      to the basal level after incubation for 24 h. The protein synthesis inhibitor,
      cycloheximide, induced Cox-2 mRNA expression and potentiated the effect of IL
      1beta. Degradation of Cox-2 mRNA was inhibited by IL-1beta, which suggests
      regulation at the posttranscriptional level. IL-1beta also induced the expression
      of Cox-2 protein, as detected by immunofluorescence staining using Cox-2-specific
      polyclonal antibodies. Further, IL-1beta-induced synthesis of prostanoids was
      blocked by a Cox-2-specific inhibitor, NS-398. In addition, hCG induced Cox-2
      mRNA expression and potentiated the effect of IL-1beta. However, in contrast to
      the rapid and transient effect of IL-1beta on Cox-2 mRNA, the effect of hCG
      followed slower kinetics. We have previously shown that hCG induces expression of
      human FP receptor mRNA in cultured human GL cells. We now show that IL-1beta
      induces FP receptor mRNA in a time- and concentration-dependent manner. Our data
      suggest that Cox-2 and FP receptor are coexpressed in freshly isolated human
      granulosa cells and that their expression is up-regulated by IL-1beta and hCG in
      cultured human GL cells.

PMID- 9275048
TI  - Activation of phospholipase D in FRTL-5 thyroid cells by forskolin and dibutyryl
      cyclic adenosine monophosphate.
AB  - We demonstrated previously that TSH activates phospholipase D (PLD) via
      stimulation of protein kinase C (PKC) in Fischer rat thyroid line (FRTL)-5
      thyroid cells. To examine the role of the cAMP pathway in the regulation of PLD,
      we studied the effects of forskolin (0-100 microM; 30 min) and dibutyryl cAMP
      (dbcAMP; 0-1 mM; 30 min) on PLD activation. FRTL-5 thyroid cells were labeled
      mainly in phosphatidylcholine with [3H]myristate followed by incubation with 200
      mM ethanol before the addition of agonist. PLD was assessed by the measurement of
      [3H]phosphatidylethanol. Forskolin (100 nM to 100 microM) and dbcAMP (100 pM to
      100 microM) increased PLD activity significantly. Maximal responses to forskolin
      and dbcAMP exceed the PLD responses produced by 100 microU/ml of TSH. To
      determine whether the effects of forskolin and dbcAMP on PLD occurred as a
      consequence of PKC activation, FRTL-5 thyroid cells were preincubated for 10 min
      with the PKC inhibitors, chelerythrine (1 microM) or calphostin C (1 microM), or
      they were pretreated for 24 h with phorbol myristate acetate (100 nM) to down
      regulate PKC. Unlike TSH-mediated PLD activation, these treatments had no effect
      on PLD activation by cAMP agonists. Forskolin (10 microM; 30 min) had no effect
      on the subcellular distribution of PKC alpha-, epsilon-, or zeta-isoforms,
      confirming the lack of involvement of PKC. The protein kinase A (PKA) inhibitors,
      H-89 (10 microM; 30 min) and dideoxyadenosine (5 nM; 10 min) significantly
      decreased the forskolin- and dbcAMP-mediated PLD activation without any effect on
      the phorbol ester-mediated PLD response. Following pretreatment with H-89 or
      dideoxyadenosine, the TSH-mediated PLD response was also significantly reduced.
      These studies indicate that forskolin and dbcAMP stimulate PLD in FRTL-5 thyroid
      cells directly via PKA without involvement of PKC. Studies of cells in the
      presence and absence of ethanol revealed approximately 60% of the phosphatidate
      plus diacylglycerol produced via TSH occurs via PLD activation. Although TSH
      mediated inositol phosphate generation occurred with similar concentrations of
      TSH that led to PLD activation, 10-fold higher TSH concentrations were required
      to increase intracellular Ca2+. These results and the lack of a rapid Ca2+
      transient following physiological TSH concentrations suggest that alternatives to
      conventional hydrolysis of phosphatidylinositol 4,5-bisphosphate may initiate PKC
      activation. Thus, the two major signal transduction systems in the FRTL-5 thyroid
      cell (PKA and PKC) appear to converge on PLD activation. Stimulation of both of
      these pathways by TSH may be required for optimal physiological activation of
      PLD.

PMID- 9275049
TI  - Relaxin increases insulin-like growth factors (IGFs) and IGF-binding proteins of
      the pig uterus in vivo.
AB  - Relaxin promotes growth of reproductive tissues, including the uterus. Although
      we have evidence of a role for insulin-like growth factor I (IGF-I) in mediating
      relaxin-induced growth of porcine granulosa cells in vitro, the mechanism of
      action by which relaxin enhances uterine growth has not been identified. To
      investigate a role for the uterine insulin-like growth factor (IGF) system in
      relaxin-induced uterine growth, we monitored the effects of relaxin on porcine
      IGFs and IGF-binding proteins (IGFBPs) in vivo. The trophic effects of relaxin on
      the uterus were elicited by administering relaxin or saline to prepubertal gilts
      every 6 h for 54 h. Three hours after the last injection, uterine flushes, uteri,
      follicular fluid, and ovaries were collected. Estradiol was measured in plasma
      and follicular fluid to confirm the prepubertal status of each animal.
      Significantly higher concentrations of uterine lumen IGF-I (P < 0.05) and IGF-II
      (P < 0.01) were observed in animals treated with relaxin. However, relaxin
      administration did not affect uterine IGF-I and -II gene expression, as
      determined by a ribonuclease protection assay and Northern analysis,
      respectively. In uterine flushes, relaxin treatment increased an IGFBP doublet
      (33 and 34.5 kDa) and IGFBP-3. The uterine IGFBP doublet was identified as IGFBP
      2 by immunoprecipitation. Plasma or follicular fluid IGFs and IGFBPs were
      unaffected by relaxin administration. In addition, relaxin did not influence IGF
      I binding to its uterine receptor. This is the first study to demonstrate
      regulation of the pig uterine IGF system by relaxin. In conclusion, the data
      point to IGF-I, IGF-II, IGFBP-2, and IGFBP-3 as putative mediators of relaxin
      induced uterine growth in the pig.

PMID- 9275050
TI  - Mothers against decapentaplegic-related protein 2 expression in avian granulosa
      cells is up-regulated by transforming growth factor beta during ovarian
      follicular development.
AB  - Although mothers against dpp (MAD) and its related proteins (MADR) are believed
      to be important components of the cell signaling pathway for the transforming
      growth factor beta (TGFbeta) superfamily, the presence and regulation of these
      signaling molecules in ovarian cells by TGFbeta is not known. In the present
      studies, we have examined the presence of MADR2 and MADR1, two members of the
      MADR family, in hen granulosa cells at different stages of follicular
      development. The influence of TGFbeta in vitro on their expression was assessed,
      particularly in the context of TGFbeta-induced down-regulation of cytosolic
      phospholipase A2 (cPLA2), a key enzyme in the biosynthesis of eicosanoids. We
      have demonstrated for the first time the presence of MADR2 and MADR1 in hen
      granulosa cells at different stages of follicular development. The expression of
      MADR2, but not of MADR1, was up-regulated by TGFbeta in vitro in a concentration-
      and time-dependent manner. Granulosa cell MADR2 expression was maximal during
      early stages of follicular development, when the granulosa cell cPLA2 system is
      most responsive to the growth factor. The changes in MADR2 expression were
      accompanied by reciprocal alterations in the expression of cPLA2. These findings
      are consistent with the hypothesis that homologous up-regulation of MADR2 in
      granulosa cells may be an important determinant in its follicular stage-specific
      responsiveness to TGFbeta and possibly in the suppression of cPLA2 gene
      transcription by the growth factor.

PMID- 9275051
TI  - Activation of the Janus kinase/STAT (signal transducer and activator of
      transcription) signal transduction pathway by interleukin-6-type cytokines
      promotes osteoblast differentiation.
AB  - We have previously established that stromal/osteoblastic cells collectively
      express receptors for all members of the cytokine subfamily that share the gp130
      signal transducer and that different receptor repertoires may be expressed at
      different stages of differentiation of this lineage. We have now used human (MG
      63) and murine (MC3T3-E1) osteoblastic cell lines as well as primary murine
      calvaria cells to test the hypothesis that these receptors mediate effects of the
      cytokines on the biology of osteoblasts. We report that as in other cell types,
      all of the osteoblastic cell models responded to interleukin-6 (IL-6)-type
      cytokines with activation of both the JAK/STAT (Janus kinase/signal transducer
      and activator of transcription) and the mitogen-activated protein kinase (MAPK)
      pathways. In addition, IL-6-type cytokines stimulated alkaline phosphatase
      activity and osteocalcin expression and inhibited (MG-63), stimulated (MC3T3-E1),
      or had no effect (calvaria cells) on the rate of cell proliferation. The ability
      of a given cell type to respond to a particular member of this family of
      cytokines was strictly dependent on the presence of the corresponding ligand
      binding subunit (alpha) of the cytokine receptor, and the magnitude of all the
      effects was closely correlated with the concentration of this subunit. The
      relative contribution of the JAK/STAT and MAPK pathways to the biological effects
      of the cytokines was evaluated using kinase inhibitors. Cytokine-mediated
      modulation of cell proliferation as well as stimulation of alkaline phosphatase
      activity were abrogated by tyrosine kinase inhibitors as well as a
      threonine/serine kinase inhibitor, but were only minimally affected by a specific
      inhibitor of MAPK phosphorylation. These results demonstrate that IL-6-type
      cytokines, besides their osteoclastogenic properties, promote differentiation of
      committed osteoblastic cells toward a more mature phenotype and that this action
      is mediated primarily via the activation of the JAK/STAT pathway.

PMID- 9275052
TI  - Involvement of the cell cycle inhibitor CIP1/WAF1 in lung alveolar epithelial
      cell growth arrest induced by glucocorticoids.
AB  - Glucocorticoids are known to impair the postnatal development of lung parenchyma
      by altering the formation of alveoli, and from the current understanding of the
      processes controlling the growth of the alveolar structure, it is likely that
      this impairment relies in large part on alteration of alveolar epithelial cell
      replication. From recent studies on the modulation of cell proliferation by
      glucocorticoids, it appears that events associated with the G1 phase of the cell
      cycle are a major target for the actions of these hormones. To gain some insights
      into the mechanisms involved in the growth arrest of lung alveolar epithelial
      cells by glucocorticoids, we focused in the present study on the effects of these
      hormones on the expression of the G1 cyclins and their cell cycle-dependent
      kinases (CDKs). We observed that when cells were blocked in their proliferation
      by dexamethasone treatment, no changes in the expression of the various G1
      cyclins, D1, D2, D3, or E, could be documented. Also, the levels of CDK2 and CDK4
      in glucocorticoid-treated cells did not exhibit significant modifications
      compared with the levels in proliferating cells. Evaluation of the activity of
      cyclin-CDK complexes showed that activation of cyclin D-CDK4 was not modified by
      dexamethasone. By contrast, differences in the activity of cyclin E-CDK2
      complexes were found, with a profound decrease in the extracts of cells growth
      arrested by dexamethasone. Studies of the factors potentially implicated in the
      inactivation of these complexes strongly suggested a role for p21CIP1, as a
      dramatic accumulation of this protein was observed in cells treated with
      dexamethasone. Moreover, changes in p21CIP1 expression appeared to be controlled
      mostly at the posttranscriptional level. Interestingly, a decrease in the levels
      of p27KIP1 could be observed. These results indicate that glucocorticoids block
      entry of alveolar epithelial cells into S phase by specifically altering the
      activation of cyclin E-CDK2 complexes through induction of the CDK inhibitor
      p21CIP1.

PMID- 9275053
TI  - Hypothalamic sites of action for testosterone, dihydrotestosterone, and estrogen
      in the regulation of luteinizing hormone secretion in male sheep.
AB  - Testosterone (T) inhibits LH secretion partly by acting at unknown sites within
      the brain to inhibit GnRH secretion. We tested the hypothesis that the preoptic
      area (POA) and arcuate-ventromedial region (ARC/VMR), areas rich in androgen and
      estrogen (E) receptors, are neural sites at which T and the T metabolites,
      dihydrotestosterone (DHT) and estrogen (E), act to suppress LH secretion.
      Bilateral guide cannulae were surgically implanted into either the POA or ARC/VMR
      of castrated male sheep. Experiments were conducted under a long day photoperiod
      to maximize the inhibitory effect of the steroids. In Exp 1, all sheep (n =
      6/site) sequentially received bilateral implants of cholesterol (CHOL), T, or E
      at each site. Jugular blood samples were taken at 10-min intervals for 4 h both
      immediately before implant insertion and 5 days later. In Exp 2, all sheep (n =
      6/site) sequentially received bilateral implants of CHOL, DHT, or E at each site
      according to a latin square design. Blood samples were taken before and 7 days
      after implant insertion. In Exp 3, which followed the same design as Exp 2,
      implants of E, T, or DHT were placed only in the ARC/VMR. In the final
      experiment, the effects of T and CHOL implants in the ARC/VMR were compared.
      Neither T, DHT, nor CHOL implants at either site affected LH secretion. In
      contrast, E treatment in the ARC/VMR suppressed mean plasma LH levels (P < 0.01),
      primarily due to an increase in interpulse interval (P < 0.01). Estrogen implants
      in the POA caused a small, but nonsignificant (P > 0.05), decrease in mean LH
      levels in the first experiment and an increase in LH interpulse interval (P <
      0.05) in the second experiment. These results suggest that the ARC/VMR and
      possibly the POA are sites at which E acts to reduce GnRH secretion in male
      sheep.

PMID- 9275054
TI  - Peroxisome proliferator-activated receptor gamma1 expression is induced during
      cyclic adenosine monophosphate-stimulated differentiation of alveolar type II
      pneumonocytes.
AB  - The primary function of lung alveolar type II cells is to synthesize pulmonary
      surfactant, a lipoprotein enriched in dipalmitoylphosphatidylcholine. Because
      type II pneumonocytes are highly lipogenic, we considered the possible role of
      the adipogenic nuclear hormone receptor, peroxisome proliferator-activated
      receptor gamma (PPARgamma), in their differentiation from epithelial cell
      precursors. A degenerate PCR-screening strategy revealed that multiple PPARs,
      including PPARgamma, are present in differentiated type II cells. A PCR-amplified
      PPARgamma DNA-binding domain was used to isolate a full-length PPARgamma1
      complementary DNA clone from a rabbit type II cell complementary DNA library.
      Although another PPARgamma isoform, PPARgamma2, is known to be highly expressed
      in adipocytes, only PPARgamma1 was detected in rabbit type II cells by use of RT
      PCR and by library screening. Rabbit PPARgamma1 has 90% nucleotide sequence
      identity and 95% amino acid identity to mouse PPARgamma1. PPARgamma1 messenger
      RNA was readily detected in total RNA isolated from rabbit type II pneumonocytes
      cultured in the presence of cAMP, which causes enlargement of the prealveolar
      ducts, accelerates the rate of type II cell differentiation, and induces
      transcription of the major surfactant associated protein, surfactant protein-A.
      PPARgamma1 messenger RNA also was detected in total RNA isolated from rabbit
      adipose tissue but not from whole adult or fetal lung, heart, or liver. By
      Western blot analysis, PPARgamma protein expression was found to occur
      coincidentally with surfactant protein-A expression during lung type II cell
      differentiation. In view of the role of PPARgamma in adipocyte differentiation
      and lipid homeostasis, we postulate that PPARgamma1 induction by cAMP plays a
      role in the differentiation and expression of lipogenic enzymes in lung type II
      cells.

PMID- 9275055
TI  - The 5'-flanking region of the ovarian promoter of the bovine CYP19 gene contains
      a deletion in a cyclic adenosine 3',5'-monophosphate-like responsive sequence.
AB  - Conversion of C19 steroids to estrogens is catalyzed by aromatase P450 (P450arom;
      the product of the CYP19 gene). In the ovary, P450arom is expressed in granulosa
      cells of both human (h) and bovine (b) follicles. After the ovulatory surge of
      gonadotropins, however, P450arom expression is maintained only in the luteinized
      granulosa cells of the human ovary and is absent from the bovine corpus luteum.
      We compared the regulation of expression of the ovary-specific human CYP19
      (hCYP19ov) and the bovine CYP19 (bCYP19ov) gene by cAMP (forskolin) and sought to
      determine whether the divergence in the expression of P450arom with the onset of
      luteinization could be explained by specific cis-acting elements present uniquely
      in the 5'-flanking DNA of the hCYP19ov or bCYP19ov gene. We, therefore, subcloned
      DNA encompassing the promoters and 5'-flanking regions of the hCYP19ov or
      bCYP19ov gene into a promoterless luciferase vector. These constructs were
      transfected into luteinized bovine granulosa cells or bovine luteal cells in
      primary culture. Neither cell type exhibits endogenous expression of bovine
      P450arom. After transfection, cells were treated with either vehicle or 25 microM
      forskolin. There was little or no increase in luciferase activity after forskolin
      treatment in cells transfected with any of the bCYP19ov constructs, whereas all
      of the corresponding hCYP19ov constructs (-693/-16 to -214/-16 bp) expressed
      reporter activity in the presence of forskolin. This dramatic difference between
      the activities of the constructs of the two species occurred despite the fact
      that there is an 88% sequence identity between the bovine and human promoters in
      the region between -214 to -16 bp. One possible explanation for this variability
      may be that the bCYP19ov gene has a 1-bp deletion in a cAMP-response element-like
      sequence (CLS) present at -208 to -201 bp in the hCYP19ov gene that we have shown
      to be critical for cAMP-stimulated transcription of hCYP19ov in the ovary. When
      this region of the bCYP19ov promoter was mutated to the hCLS, a partial
      restoration in luciferase activity was observed after forskolin treatment.
      Therefore, these results suggest that another sequence in this -214 bp region of
      the bCYP19ov gene is also contributing to the lack of expression of P450arom
      after luteinization in the bovine ovary. This lack of expression of the bCYP19ov
      gene may be due to the presence of a repressive trans-acting factor expressed
      with the onset of luteinization of the bovine granulosa cell. These results
      further suggest that in the cow, elements upstream of those employed by the
      hCYP19ov gene may have been recruited to facilitate regulated expression of the
      bCYP19ov gene in the absence of a functional CLS.

PMID- 9275056
TI  - 1,25-dihydroxyvitamin D3 regulates estrogen metabolism in cultured keratinocytes.
AB  - Local estrogen metabolism may play an important role in modulating cell
      development in peripheral tissues such as breast, adipose, and bone. C19
      androgens are converted to C18 estrogens by the enzyme aromatase, overexpression
      of which is associated with breast cancer. Interconversion of active estradiol
      (E2) to inactive estrone is controlled by various isoforms of the enzyme 17beta
      hydroxysteroid dehydrogenase (17betaHSD). We have studied the expression of these
      two enzymes in human keratinocytes and report rapid changes in 17betaHSD activity
      in response to treatment with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3].
      Keratinocytes cultured in serum-free medium showed aromatase activity of 2.5
      fmol/h x mg cell protein, which was unaffected by any culture treatment. A much
      higher level of 17betaHSD activity was observed in the keratinocytes,
      predominantly conversion of E2 to estrone (approximately 120 pmol/h x mg cell
      protein). This inactivation of E2 increased in a dose-dependent fashion after
      treatment of the cells with antiproliferative doses of 1,25-(OH)2D3 (0.1-200 nM).
      The effect of 1,25-(OH)2D3 on 17betaHSD activity was enhanced by simultaneous
      treatment with dexamethasone, which also increased the antiproliferative action
      of 1,25-(OH)2D3. Reverse transcription-PCR and Northern analysis showed that
      keratinocytes expressed messenger RNA for three 17betaHSD isoenzymes (types I,
      II, and IV). Treatment with 1,25-(OH)2D3 (10 nM for 20 h) resulted in the up
      regulation of messenger RNA levels for type 2 17betaHSD. Further RNA studies
      combined with E2 binding experiments demonstrated the presence of estrogen
      receptors in the cultured keratinocytes. These data indicate that keratinocytes
      are potential targets for systemically or locally produced estrogens, which may,
      in turn, play a key role in the development of normal skin. In particular, we
      propose that 17betaHSD isoenzymes are key target genes for 1,25-(OH)2D3 in
      keratinocytes and may be an important feature of the antipsoriatic effects of
      vitamin D and its analogs.

PMID- 9275057
TI  - Decreased cyclin A2 and increased cyclin G1 levels coincide with loss of
      proliferative capacity in rat Leydig cells during pubertal development.
AB  - Postnatal development of Leydig cells can be divided into three distinct stages
      of differentiation: initially they exist as mesenchymal-like progenitors (PLC) by
      day 21; subsequently, as immature Leydig cells (ILC) by day 35, they acquire
      steroidogenic organelle structure and enzyme activities but metabolize most of
      the testosterone they produce; finally, as adult Leydig cells (ALC) by day 90
      they actively produce testosterone. The aims of the present study were to
      determine whether changes in proliferative capacity are associated with
      progressive differentiation of Leydig cells, and if the proliferative capacity of
      Leydig cells is controlled by known hormonal regulators of testosterone
      biosynthesis: LH, insulin-like growth factor I (IGF-I), androgen, and estradiol
      (E2). Isolated PLC, ILC, and ALC were cultured in DMEM/F-12 for 24 h followed by
      an additional 24 h in the presence of LH (1 ng/ml), IGF-I (70 ng/ml), 7alpha
      methyl-19-nortestosterone (MENT, 50 nM), a synthetic androgen that is not
      metabolized by 5alpha-reductase, or E2 (50 nM). Proliferative capacity was
      measured by assaying [3H]thymidine incorporation and labeling index (LI).
      Messenger RNA (mRNA) and protein levels for cyclin A2 and G1, which are putative
      intracellular regulators of Leydig cell proliferation and differentiation, were
      measured by RT-PCR and immunoblotting, respectively. Thymidine incorporation was
      highest in PLC (9.24 +/- 0.21 cpm/10(3) cell, mean +/- SE), intermediate in ILC
      (1.74 +/- 0.07) and lowest in ALC (0.24 +/- 0.03). Similarly, LI was highest in
      PLC (13.42 +/- 0.30%, mean +/- SE), intermediate in ILC (1.95 +/- 0.08%), and
      undetectable in ALC. Cyclin A2 mRNA levels, normalized to ribosomal protein S16
      (RPS16), were highest in PLC (2.76 +/- 0.21, mean +/- SE), intermediate in ILC
      (1.79 +/- 0.14), and lowest in ALC (0.40 +/- 0.06). In contrast, cyclin G1 mRNA
      levels were highest in ALC (1.32 +/- 0.16), intermediate in ILC (0.47 +/- 0.07),
      and lowest in PLC (0.12 +/- 0.02). The relative protein levels of cyclin A2 and
      G1 paralleled their mRNA levels. Increased proliferative capacity was observed in
      PLC and ILC, but not ALC, after treatment with either LH or IGF-I. Treatment with
      MENT increased proliferative capacity only in ILC and had no effect in any other
      group. Treatment with E2 decreased proliferative capacity in PLC but not in ILC
      or ALC. The changes in proliferative capacity after hormonal treatment paralleled
      cyclin A2 mRNA and were the inverse of cyclin G1 mRNA levels. We conclude that:
      1) decreased cyclin A2 and increased cyclin G1 are associated with the withdrawal
      of the Leydig cell from the cell cycle; 2) the proliferative capacity of Leydig
      cells is regulated differentially by hormones and is progressively lost during
      postnatal differentiation.

PMID- 9275058
TI  - Extrathyroidal effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on thyroid hormone
      turnover in male Sprague-Dawley rats.
AB  - Treatment of rats with different polyhalogenated aromatic hydrocarbons strongly
      decreases plasma T4, with little or no decrease in plasma T3. The extrathyroidal
      effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on thyroid hormone turnover
      were studied by i.p. administration of a single dose of 10 microg TCDD/kg BW or
      vehicle (corn oil) to euthyroid (Eu) rats, thyroidectomized (Tx) rats, and Tx
      rats infused with 1 microg T4 (Tx+T4) or 0.4 microg T3 (Tx+T3)/100 g BW x day by
      osmotic minipumps. Tx rats showed decreased plasma T4 and T3 and increased plasma
      TSH levels, decreased hepatic type I deiodinase (D1) and malic enzyme activities,
      and increased brain type II deiodinase (D2) activities. All parameters were
      largely restored to Eu levels in Tx+T4 rats and, except for plasma T4 and brain
      D2 activity, in Tx+T3 rats, validating the thyroid hormone-replaced Tx rats as
      models to study the peripheral effects of TCDD. Three days after TCDD
      administration, plasma T4 and free T4 levels were significantly reduced in Eu and
      Tx+T4 rats, and plasma T3 was significantly reduced in Tx+T3, but not in Eu or
      Tx+T4 rats. Plasma TSH was not affected by TCDD in any group. Hepatic T4 UDP
      glucuronyltransferase (UGT) activity was induced approximately 5-fold by TCDD,
      whereas T3 UGT activity was only increased by about 20% (P = NS) in the different
      groups. TCDD produced an insignificant decrease in liver D1 activity in Tx rats
      and an insignificant increase in brain D2 activity in Tx rats and hormone
      replaced Tx rats. Hepatic malic enzyme activity was significantly increased by
      TCDD in all groups, except Tx rats. These results strongly suggest that the
      thyroid hormone-decreasing effects of TCDD are predominantly extrathyroidal and
      mediated by the marked induction of hepatic T4 UGT activity.

PMID- 9275059
TI  - T-type calcium channels facilitate insulin secretion by enhancing general
      excitability in the insulin-secreting beta-cell line, INS-1.
AB  - The present study addresses the function of T-type voltage-gated calcium channels
      in insulin-secreting cells. We used whole-cell voltage and current recordings,
      capacitance measurements, and RIA techniques to determine the contribution of T
      type calcium channels in modulation of electrical activity and in stimulus
      secretion coupling in a rat insulin secreting cell line, INS-1. By employing a
      double pulse protocol in the current-clamp mode, we found that activation of T
      type calcium channels provided a low threshold depolarizing potential that
      decreased the latency of onset of action potentials and furthermore increased the
      frequency of action potentials, both of which are abolished by administration of
      nickel chloride (NiCl2), a selective T-type calcium channel blocker. Moreover
      application of high frequency stimulation, as compared with low frequency
      stimulation, caused a greater change in membrane capacitance (deltaCm),
      suggesting higher insulin secretion. We demonstrated that glucose stimulated
      insulin secretion in INS-1 is reduced dose dependently by NiCl2. We conclude that
      T-type calcium channels facilitate insulin secretion by enhancing the general
      excitability of these cells. In light of the pathological effects of both hypo
      and hyperinsulinemia, the T-type calcium channel may be a therapeutic target.

PMID- 9275060
TI  - Reduced response of the hypothalamo-pituitary-adrenal axis to alpha1-agonist
      stimulation during lactation.
AB  - To determine whether altered noradrenergic activation of the hypothalamo
      pituitary-adrenal (HPA) axis contributes to the attenuated neuroendocrine
      response to stress observed during lactation, the effect of
      intracerebroventricular injection of the alpha1-agonist methoxamine (100 microg)
      was compared between virgin and lactating rats. Virgin rats showed significant
      increases in plasma corticosterone after methoxamine, reaching 317 +/- 44 ng/ml
      at 10 min and remaining significantly elevated for more than 120 min, but
      lactating rats showed no significant increase in corticosterone levels.
      Furthermore, methoxamine induced an increase in paraventricular nucleus (PVN) CRF
      messenger RNA expression in virgin, but not lactating, animals. Both groups of
      rats exhibited comparable elevations in plasma PRL after methoxamine treatment.
      Arginine vasopressin messenger RNA expression within the parvocellular PVN was
      greater in the lactating animals than in the virgin controls, but methoxamine
      injection was without further effect. Studies performed on ovariectomized virgin
      rats and ovariectomized rats receiving estradiol or progesterone replacement
      failed to reproduce the attenuated HPA responses seen after methoxamine
      treatment, although methoxamine-induced PRL levels were greatly increased by
      estradiol, probably arising from an effect on hormone synthesis. In vitro
      electrophysiological recordings of PVN neurons in hypothalamic slices from
      proestrous virgin and lactating rats showed that 45-52% of neurons in both groups
      exhibited excitatory responses to 10(-4) M methoxamine, but there was a
      differential response to 10(-5) M methoxamine, with PVN neurons from lactating
      animals failing to show a response. These data show a selective down-regulation
      of alpha1-mediated activation of the HPA axis in lactating animals. This may
      contribute to the attenuated stress-induced activation of the HPA axis during
      lactation.

PMID- 9275061
TI  - Central action of adrenomedullin to inhibit gastric emptying in rats.
AB  - The central action of human adrenomedullin (AM) to influence gastric emptying and
      the peripheral mechanisms involved were studied in conscious rats. The 20-min
      rate of gastric emptying of a methylcellulose solution was assessed after
      intracisternal (i.c.) injection of AM or rat alpha-calcitonin gene-related
      peptide (alphaCGRP). AM and alphaCGRP dose-dependently inhibited gastric emptying
      with i.c. ED50 values of 120 and 100 pmol, respectively. Human proadrenomedullin
      N-terminal 20 peptide (150-600 pmol, i.c.) and AM (150 pmol, i.v.) had no effect.
      The inhibitory actions of AM and alphaCGRP (150 pmol, i.c.) were completely
      blocked by the CGRP antagonist, human CGRP-(8-37) injected i.c. at 30 microg, but
      not at 15 microg. The CRF antagonist, [D-Phe12,Nle(21,38),C(alpha)MeLeu37]CRF-(12
      41) (10 microg/rat) injected i.c. prevented i.c. rat/human CRF (150 pmol)-induced
      53% inhibition of gastric emptying while not modifying the effect of AM. The
      action of AM (150 pmol, i.c.) was abolished by bilateral adrenalectomy or the
      beta-adrenergic blocker, propranolol (1 mg/kg, i.p.), but was not altered by
      indomethacin (5 mg/kg, i.p.) or subdiaphragmatic vagotomy. These results indicate
      that i.c. AM and alphaCGRP equipotently inhibit gastric emptying through
      mechanisms similarly antagonized by a high dose of CGRP-(8-37). The central AM
      action is mediated through adrenal-dependent, beta-adrenergic pathways
      independently from activation of central CRF receptors.

PMID- 9275062
TI  - Oncogene transformation of PC Cl3 clonal thyroid cell line induces an autonomous
      pattern of proliferation that correlates with a loss of basal and stimulated
      phosphotyrosine phosphatase activity.
AB  - The effects of the stable expression of E1A and/or middle T oncogenes on the
      proliferative activity of PC Cl3 normal thyroid cells are reported. The
      proliferation of PC Cl3 cells is mainly regulated by insulin and TSH in a
      stimulatory way and by somatostatin in an inhibitory fashion. The transformed
      cell lines, named PC Py and PC E1A Py, show an autonomous pattern of
      proliferation. The blockade of phosphotyrosine phosphatase activity with vanadate
      increased the proliferation rate of PC Cl3 under basal and stimulated conditions
      and completely prevented the inhibitory activity of somatostatin, suggesting that
      in PC Cl3 cells, a tonic tyrosine phosphatase activity regulates basal and
      stimulated proliferation, and that a somatostatin-dependent increase in this
      activity may represent a cytostatic signal. Conversely, in both PC Py and PC E1A
      Py, vanadate did not modify basal and stimulated proliferation. We analyzed
      tyrosine phosphatase activity in the different cell lines basally and under
      conditions leading to the arrest of cell proliferation: confluence (contact
      inhibition), growth factor deprivation (starvation), and somatostatin treatment.
      Under basal conditions, tyrosine phosphatase activity was significantly lower in
      PC Py and PC E1APy cell lines than that in the normal cells. The inhibition of
      the proliferation induced by contact inhibition or somatostatin treatment was
      accompanied by an increase in tyrosine phosphatase activity only in PC Cl3 cells.
      The reduction in tyrosine phosphatase activity in PC E1APy cells correlated with
      a significant reduction in the expression of R-PTP eta, a tyrosine phosphatase
      cloned from PC Cl3 cells. Conversely, the expression of another receptor-like
      PTP, PTP mu, was unchanged. Thus, PTP eta may be a candidate to mediate
      inhibitory signals (i.e. activation of somatostatin receptors or cell to cell
      contact) on the proliferative activity of PC Cl3 cells, and the reduction of its
      expression in the transformed cell lines may lead to an alteration in the control
      of cell proliferation.

PMID- 9275063
TI  - Steroid-involved transcriptional regulation of human genes encoding prostatic
      acid phosphatase, prostate-specific antigen, and prostate-specific glandular
      kallikrein.
AB  - We have compared the steroid regulation of human genes encoding prostatic acid
      phosphatase (hPAP), prostate-specific antigen (hPSA), and prostate-specific
      glandular kallikrein (hK2) at the level of transcription. Reporter constructs of
      hPAP promoter covering the region -734/+467 were functional in both prostatic
      (LNCaP and PC-3) and nonprostatic (CV-1) cell lines in transient transfections.
      hPAP -231/+50 with eight identified transcription factor-binding sites showed the
      highest, and hPAP -734/+467 showed the lowest transcriptional activity in CV-1
      cells. The hPAP promoter could not be induced with androgen, glucocorticoid, or
      progesterone, contrary to the hPSA (-620/+40) and hK2 (-493/+27) promoters in PC
      3 cells cotransfected with the respective steroid receptor expression vector.
      Therefore, steroids cannot directly regulate hPAP gene expression via receptor
      binding to steroid response elements at -178 and +336, which have been shown to
      have androgen receptor-binding ability in vitro. Glucocorticoid was the most
      powerful activator of the hPSA construct at 10-nM steroid concentrations. On the
      contrary, glucocorticoid stimulation of the transcriptional activity of the hK2
      construct was the weakest among the tested steroids. The results indicate that
      the steroid response elements in the proximal promoters of hPSA and hK2 genes are
      not androgen specific, offering the molecular basis for the expression of these
      genes outside the prostate in tissues containing steroid receptors.

PMID- 9275064
TI  - Neuronal mitochondrial morphology and transmembrane potential are severely
      altered by hypothyroidism during rat brain development.
AB  - We recently demonstrated that thyroid hormone is an important regulator of
      mitochondrial gene expression during brain development. To gain further insights
      into the consequences of this regulation, we have performed functional and
      structural analysis of brain mitochondria from control and hypothyroid neonatal
      rats. Flow cytometric analysis showed a significant decrease in the mitochondrial
      transmembrane potential in hypothyroid animals compared with controls, which was
      reversed after 48 h, but not after 2 h, of thyroid hormone administration,
      suggesting that the functional alterations observed are the consequence of
      changes in mitochondrial gene expression. In addition, band shift studies showed
      a protein bound to the rat mitochondrial promoter differentially regulated by
      thyroid state. Electron microscopic analysis of cerebral cortex, striatum, and
      hippocampus revealed marked differences in the morphology of neuronal
      mitochondria from control and hypothyroid neonates. Hypothyroid mitochondria
      presented a decrease in the area of the inner membrane plus cristae in all areas
      studied, except for the hippocampal CA1 neurons and nonneuronal cell types. The
      observations reported here provide a basis for the known biochemical action of
      thyroid hormone on brain development.

PMID- 9275065
TI  - Androgen receptor-mediated antagonism of estrogen-dependent low density
      lipoprotein receptor transcription in cultured hepatocytes.
AB  - Postmenopausal women receiving hormone replacement therapy have a lower risk of
      coronary heart disease than women who do not receive hormone treatment. Multiple
      mechanisms are likely to underlie estrogen's cardioprotective action, including
      lowering of plasma low density lipoprotein (LDL) cholesterol. Using an in vitro
      system exhibiting normal regulation of LDL receptor (LDLR) gene transcription, we
      show that 17beta-estradiol activates the LDLR promoter in transiently transfected
      HepG2 cells. LDLR activation by estrogen in HepG2 cells is dependent on the
      presence of exogenous estrogen receptor, and the estrogen-responsive region of
      the LDLR promoter colocalizes with the sterol response element previously
      identified. The estrogen response is concentration dependent, saturable, and
      sensitive to antagonism by estrogen receptor antagonists. Further, we show that
      compounds with androgen receptor agonist activity attenuate the estrogen-induced
      up-regulation of LDLR in our model system. Progestins with androgen receptor
      agonist activity, such as medroxyprogesterone acetate, also suppress estrogen's
      effects on LDLR expression through their androgenic properties. Characterization
      of the interplay between these hormone receptors on the LDLR in vitro system may
      allow a better understanding of the actions of sex steroids on LDLR gene
      expression and their roles in cardiovascular disease.

PMID- 9275066
TI  - Suppression of thyrotropin receptor-G protein-phospholipase C coupling by
      activation of protein kinase C in thyroid carcinoma cells.
AB  - In human thyroid follicular cells TSH exerts its action on growth and function at
      least via two distinct pathways, the adenylate cyclase cascade and the
      phospholipase Cbeta (PLCbeta)-mediated inositol phosphate generation. We
      investigated the effect of TSH on activation of phosphoinositide hydrolysis and
      inositol phosphate generation by PLCbeta in HTh74 thyroid carcinoma cells that
      express functional TSH receptors and in HTC-TSHr thyroid carcinoma cells that are
      devoid of endogenous TSH receptors but express recombinant human TSH receptors.
      In both cell lines, TSH up to concentrations of 300 mU/ml failed to stimulate myo
      inositol 1,4,5-trisphosphate and myo-inositol-tetrakisphosphate generation, but
      led to a decrease in these compounds within 1 min of stimulation. However, ATP
      and bradykinin increased concentrations of inositol phosphates in both thyroid
      carcinoma cell lines. In contrast, in differentiated FRTL5 thyroid cell line and
      CHO-TSHr cell line expressing recombinant human TSH receptors, TSH elicited a
      significant increase in myo-inositol 1,4,5-trisphosphate and its metabolic
      derivatives. However, when HTC-TSHr cells were pretreated with calphostin C or
      staurosporine, inhibitors of protein kinase C, a TSH concentration of 20 mU/ml
      enhanced generation of inositol phosphates in these cells. From our data we
      conclude that in HTC-TSHr and HTh74 thyroid carcinoma cells, the coupling within
      the TSH receptor-Gq protein-PLCbeta signaling pathway is impaired compared to
      that in nontransformed cells. It is conceivable that this is at least in part
      dependent on the level of protein kinase C activation in these cells.

PMID- 9275067
TI  - Proteolysis of insulin-like growth factors (IGF) and IGF binding proteins by
      cathepsin D.
AB  - Various proteinases have been postulated to function in limited proteolysis of
      insulin-like growth factor binding proteins (IGFBPs) contributing to the
      regulation of IGF bioavailability. In this study, we report on the in vitro
      degradation of IGFs and IGFBPs by the purified acidic aspartylprotease cathepsin
      D that has been shown to proteolyze IGFBP-3. Recombinant human [125I] IGFBP-1 to 
      5 were processed by cathepsin D to fragments of defined sizes in a concentration
      dependent manner, whereas IGFBP-6 was not degraded. Ligand blotting revealed that
      none of the IGFBP-1 or -3 fragments formed by cathepsin D retain their ability to
      bind IGF. By N-terminal sequence analysis of nonglycosylated IGFBP-3 fragments
      produced by cathepsin D, at least four different cleavage sites were identified.
      Some of these cleavage sites were identical or differed by one amino acid from
      sites used by other IGFBP proteases described. The IGFBP-3 and -4 cleavage sites
      produced by cathepsin D are located in the nonconserved central region. IGF-I and
      -II, but not the unrelated platelet-derived growth factor BB, were degraded by
      cathepsin D in a time and concentration-dependent manner. We speculate that the
      major functional site of cathepsin D is intracellular and may be involved 1) in
      the selected clearance either of IGFBP or IGFs via different endocytic pathways
      or 2) in the general lysosomal inactivation of the IGF system.

PMID- 9275069
TI  - Characterization of truncated insulin-like growth factor-binding protein-2 in
      human milk.
AB  - Truncated forms of insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2)
      have been purified from human milk and shown to retain partial IGF-binding
      activity. By affinity chromatography on agarose-IGF-I and HPLC, truncated IGFBP-2
      of apparent Mr 14,000-16,000 resolved into two peaks. Both peaks bound
      radioiodinated IGF-II on ligand blotting. Within both peaks, two sequences were
      identified, starting at Gly169 and Lys181 of hIGFBP-2 (predicted Mr, 13,786 and
      12,502, respectively, if both extend to Gln289). Mass spectrometry of a fraction
      predominantly containing Gly169 peptides yielded two major species, 13,840 and
      13,425 Mr. Prolonged incubation of radioiodinated recombinant human (rh) IGFBP-2
      with human milk failed to reveal any degradation, suggesting the formation of the
      fragments within the mammary gland. By solution binding assay, truncated IGFBP-2
      showed less than 10% binding of [125I]IGF-I and 25% binding of [125I]IGF-II at pH
      7.0 compared with rhIGFBP-2. No binding activity was seen at pH 4.0, in contrast
      to intact IGFBP-2, which showed peak binding from pH 4.0 to at least pH 9.0. The
      IGF-II association constant for truncated IGFBP-2 (6.5 nM(-1)) was 10-fold lower
      than that for intact IGFBP-2 (58 nM(-1)). Des(1-6)-IGF-II was totally inactive in
      displacing IGF-II tracer from the IGFBP-2 fragment, but displaced tracer from
      rhIGFBP-2 with 10% the activity of IGF-II. Thus, the amino-terminal hexapeptide
      of IGF-II is required for interaction with the carboxy-terminal domain of IGFBP
      2. The presence of active IGFBP-2 fragments in milk suggests a role for milk
      IGFBP-2 in modifying IGF activity in the neonatal gut.

PMID- 9275068
TI  - Role of gonadal steroids in determining sexual differences in expression of Fos
      related antigens in tyrosine hydroxylase-immunoreactive neurons in subdivisions
      of the hypothalamic arcuate nucleus.
AB  - Dual immunohistochemistry was employed to examine the role of gonadal steroids in
      determining sexual differences in the expression of Fos and its related antigens
      (FRA) in tuberoinfundibular dopaminergic (TIDA) neurons located in the
      dorsomedial (DM-) and ventrolateral (VL-) subdivisions of the arcuate nucleus
      (ARC). In the DM-ARC, there was no sexual difference in the number of tyrosine
      hydroxylase (TH)-immunoreactive (-IR) perikarya, but the number of these
      containing FRA-IR was greater in females than in males in all but the most caudal
      region. In the VL-ARC, there were more TH-IR perikarya in males than in females,
      but there was no sexual difference in the numbers of those containing FRA-IR
      throughout the entire rostrocaudal extent of this nucleus. Ovariectomy decreased
      the number of TH-IR perikarya containing FRA-IR in the DM-ARC, but not in the VL
      ARC, whereas orchidectomy increased the number of TH-IR perikayra containing FRA
      IR in both the DM-ARC and VL-ARC. These gonadectomy-induced effects were reversed
      by estrogen and testosterone, respectively. These results reveal gonadal steroid
      dependent sexual differences in the regulation of immediate early gene expression
      in anatomically discrete subpopulations of TIDA neurons. In females, estrogen
      stimulates FRA expression in TIDA neurons in the DM-ARC, whereas in males,
      testosterone inhibits FRA expression in TIDA neurons in both the DM-ARC and the
      VL-ARC.

PMID- 9275070
TI  - Direct actions of kit-ligand on theca cell growth and differentiation during
      follicle development.
AB  - The direct actions of kit-ligand/stem cell factor (KL) in developing ovarian
      follicles were investigated. Previous studies have shown that granulosa cells
      express KL that can support oocyte development. The current study demonstrates
      that KL can also act directly on theca cells to promote cellular growth and
      differentiation. Through RT-PCR analysis it was shown that bovine granulosa cells
      express KL, and theca cells express the receptor c-kit. Bovine theca interna
      cells were isolated and cultured in serum-free conditions to study KL actions. KL
      stimulated theca cell growth in a dose-dependent manner as measured by
      [3H]thymidine incorporation into DNA when cells were cultured under subconfluent
      conditions. KL had no effect on theca cell androstenedione or progesterone
      production under these growth-permissive conditions. In contrast, KL stimulated
      theca cell androstenedione production but had no effect on progesterone
      production when theca cells were cultured under confluent (non-growth-permissive)
      conditions. Estradiol (10(-7) M) and human CG (100 ng/ml) were used as controls
      and regulated theca cell steroid production at any cell density. These results
      demonstrate that KL can directly stimulate theca cell growth and steroid
      production during follicular development. The observation that KL stimulated
      androstenedione production but not progesterone production suggests that KL
      promotes a follicular phase differentiated state in theca cells. The potential
      regulation of KL and c-kit expression during follicular development was studied
      using a specific quantitative RT-PCR procedure. Total RNA from granulosa cells
      (for KL) and theca cells (for c-kit) was examined from small (<5 mm), medium (5
      10 mm), and large (>10 mm) size follicles. Steady state levels of KL messenger
      RNA were highest in granulosa cells from large size follicles and lowest in small
      and medium size follicles. No differences were observed in the steady state
      levels of c-kit messenger RNA in theca cells from small, medium, or large size
      follicles. The observation that KL expression is highest in large size follicles
      suggests that KL may be important for increased growth and steroid production in
      large and dominant follicles. Observations demonstrate that KL can dramatically
      alter theca cell function and support the hypothesis that local granulosa-theca
      cell interactions play an important role in regulating cellular function within
      ovarian follicles. This study identifies KL as the first granulosa cell-derived
      growth factor that can directly stimulate theca cell growth and androstenedione
      production in the absence of gonadotropins.

PMID- 9275071
TI  - Desensitization of AT1 receptor-mediated cellular responses requires long term
      receptor down-regulation in bovine adrenal glomerulosa cells.
AB  - Angiotensin II (Ang II) regulates aldosterone production in bovine adrenal
      glomerulosa cells by interacting with the AT1 receptor. This receptor is coupled
      to a G protein that controls the activity of phospholipase C. With a primary
      culture of bovine adrenal glomerulosa cells, we evaluated the desensitization of
      cellular responses after pretreatment with Ang II. When cells were pretreated for
      30 min with 1 microM Ang II at 37 C, we observed a 48% loss of [125I]Ang II
      binding activity. Scatchard analysis revealed that this decreased binding
      activity corresponded to a 53% loss of the total number of binding sites. This
      phenomenon was time dependent, with a t(1/2) of 20 min, and a maximal loss of 76%
      of the total binding sites was observed after 14 h. A time-dependent decrease in
      AT1 receptor messenger RNA levels was also observed after pretreatment with 1
      microM Ang II for 12-24 h. Taken together, these results are interpreted as a
      down-regulation of the AT1 receptor. Desensitization of phospholipase C activity
      under similar conditions was, however, a slower process, with a t(1/2) of 9 h and
      a maximal response reduction of 83% observed after 24 h. Dose-response
      experiments indicated that maximal phospholipase C desensitization was obtained
      in the presence of 1 microM Ang II, with an EC50 of 90 nM. The desensitization
      was of a homologous nature, as a 24-h pretreatment with Ang II did not affect
      bradykinin-induced inositol phosphate production. A 24-h pretreatment with 1
      microM Ang II also significantly desensitized the steroidogenic effect of Ang II
      and the potentiating effect of Ang II on ACTH-induced cAMP production. Lower
      concentrations of Ang II (10 nM) did not produce any desensitizing effect on
      these two parameters. This study provides evidence that glomerulosa cells are
      functionally resistant to short term desensitization of the AT1 receptor and that
      long term down-regulation with high concentrations of Ang II is needed to
      desensitize AT1-mediated cellular responses.

PMID- 9275073
TI  - Circadian variation in basal plasma corticosterone and adrenocorticotropin in the
      rat: sexual dimorphism and changes across the estrous cycle.
AB  - Sexual dimorphism in the rat hypothalamic-pituitary-adrenal axis was investigated
      by determination of plasma corticosterone and immunoreactive (I-) ACTH in males
      and in females at each stage of the estrous cycle. A serial blood-sampling
      technique enabled assessment of covariation of the two hormones across the full
      circadian range of their concentrations within individual animals. Distinct
      diurnal rhythms in plasma corticosterone were evident in all rats, and the degree
      and timing of this rhythmicity, determined by cosinor analyses, did not vary with
      gender or cycle stage. There were, however, marked differences in absolute levels
      of corticosterone across the estrous cycle, with the average daily concentration
      (mesor) increasing progressively from a minimum at estrus (129 +/- 11 ng/ml) to a
      maximum 3 days later at proestrus (246 +/- 14 ng/ml). The mesor corticosterone
      value in male rats (102 +/- 21 ng/ml) was not different from that in estrous
      females, but was lower than that in females at all other stages of the cycle. In
      contrast, no gender- or cycle-related differences were detected in absolute
      levels of I-ACTH, although distinct diurnal rhythms, synchronous with those for
      corticosterone, were evident in all groups. Accordingly, a strong and positive
      within-rat relationship between plasma corticosterone and I-ACTH was observed in
      all groups, but there was a clear shift in the nature of this relationship across
      the estrous cycle, such that the slope (i.e. concentration of plasma
      corticosterone per unit concentration of I-ACTH) was minimal in males and estrous
      females and maximal in proestrous females. In conclusion, this study shows that
      the extent of sexual dimorphism in resting plasma corticosterone levels is
      dependent on estrous cycle stage, being absent at estrus and maximal at
      proestrus. Moreover, this variation in plasma corticosterone was not accompanied
      by corresponding changes in plasma I-ACTH, suggestive of cycle-related changes in
      responsiveness of the adrenal cortex to trophic stimulation.

PMID- 9275072
TI  - A novel estrogen-enhanced transcript identified in the rat uterus by differential
      display.
AB  - Estrogen exerts its physiological effects in the uterus by inducing a cascade of
      transcriptional events; however, the number of genes known to be directly
      activated by estrogen in the uterus is small. In this study, immature
      ovariectomized rats were treated with estrogen or vehicle, and 3 h later the
      uterine horns were flushed to extract epithelial RNA. This RNA was used in the
      differential display technique to search for estrogen-responsive genes. Products
      of reverse transcriptase-PCR, made with pairs of arbitrary and oligo
      deoxythymidine primers, were separated on denaturing polyacrylamide gels;
      candidate bands were excised and reamplified to produce probes for use in
      Northern blot analysis and screening of a lambda gt10 complementary DNA library
      made from rat uterus. A novel estrogen-enhanced transcript, designated EET-1, was
      identified from a differential display band, and the estrogen sensitivity of its
      expression was verified in Northern analysis. Characterization of EET-1
      expression in the uterus showed that estrogen treatment resulted in a rapid and
      transient increase in EET-1 messenger RNA; steady state levels peaked between 2-3
      h, returning to basal levels by 6 h. This increase was not abolished by
      pretreatment with cycloheximide, indicating that induction of EET-1 is a primary
      response to estrogen. Induction was specific to estrogen when extracts of whole
      uterus were examined; in the epithelium, there was also a slight response to
      progesterone. Expression of the gene was found in all organs surveyed; however,
      hormonal regulation was observed only in tissues of the reproductive tract and in
      the kidney. Analysis of cloned EET-1 complementary DNA revealed a 2008-base
      sequence that showed 61% identity with a reported transcript that encodes a
      protein that plays a role in phorbol ester-induced regulation of the tumor
      necrosis factor-alpha gene. Potential casein kinase-2 and protein kinase C
      phosphorylation sites and a cysteine-rich region were identified in the amino
      acid sequence deduced from EET-1. Thus, it appears that EET-1 represents a
      primary estrogen response gene that may code for a phosphorylated protein
      involved in gene regulation through a protein kinase C-activated pathway.

PMID- 9275074
TI  - Multiple extracellular signals promote osteoblast survival and apoptosis.
AB  - Programed cell death (PCD) or apoptosis is a naturally occurring cell suicide
      pathway induced in a variety of cell types. In many cases, PCD apparently arises
      as a result of competition for limiting amounts of survival signals. In this
      study, we have investigated the potential role of growth factors (GF), cytokines,
      and osteotropic hormones on osteoblast survival in vitro. Our results indicate
      that in the absence of any of these factors, osteoblasts rapidly undergo PCD, as
      determined by cell morphology, mitochondrial function, and nuclei fragmentation.
      Osteoblast survival was promoted by insulin-like growth factor I (IGF-I), IGF-II,
      insulin, and basic fibroblast growth factor (bFGF). Platelet-derived growth
      factor had no effect on osteoblast survival, but this GF potentiated the survival
      promoting effects of IGF-I, IGF-II, and insulin. A similar effect occurred when
      bFGF was added in combination with either of the IGFs or insulin. The effects of
      the IGFs were blocked by alphaIR-3, an antibody to the type I IGF receptor,
      whereas the effects of insulin were only partially blocked. This antibody blocked
      the potentiating effects of platelet-derived growth factor on IGF-I-mediated
      osteoblast survival, but only partially blocked those of bFGF. Although a 100%
      survival of osteoblasts was seen in the presence of 2% FCS, the highest level
      attained by any of the above GF combinations was approximately 75%. The monocyte
      derived factor, tumor necrosis factor-alpha (TNF alpha) was the only agent that
      enhanced PCD in this study. These results suggest that osteoblast survival is
      promoted by those GFs sequestrated in bone matrix and that the type I, but not
      the type II, IGF receptor is involved in the response. Our data also indicate
      that other unidentified GFs or components of the extracellular matrix may be
      involved in promoting osteoblast survival and that TNF alpha may abrogate their
      effects in vivo. We propose that these GFs may be released from bone matrix
      during phases of bone resorption and promote osteoblast survival, thereby playing
      an important role in bone remodeling, and that PCD induced by TNF alpha may
      contribute to the bone loss in inflammatory bone disease.

PMID- 9275075
TI  - Leptin inhibition of the hypothalamic-pituitary-adrenal axis in response to
      stress.
AB  - Leptin is a newly identified protein hormone that is synthesized and secreted by
      adipose tissue. Absence of the mature hormone is responsible for the obese
      phenotype of ob/ob mice. The hypothalamic-pituitary-adrenal axis (HPAA) is
      activated in ob/ob mice, and chronic administration of leptin to ob/ob mice
      decreases plasma corticosterone levels, suggesting that the adipose hormone is
      capable of inhibiting the HPAA. The aim of this study was to determine whether
      leptin feeds back acutely to inhibit the HPAA of normal mice and rats. Male C57BL
      mice were injected ip with 100 microl saline and 2 or 4 microg/g BW mouse leptin
      in saline vehicle, and 4 h later they were subjected to 2 h of restraint stress
      by taping the hind limbs together or no stress. Hind leg restraint stimulated the
      HPAA as measured by significant (P < 0.05) elevation of both ACTH and
      corticosterone. Pretreatment with recombinant mouse leptin blocked the stress
      mediated stimulation of both plasma hormones. To determine whether this
      inhibition was exerted at the hypothalamic level through inhibition of CRH, we
      studied leptin action on isolated rat hypothalami perifused with Krebs-Ringer
      buffer containing glucose (5.5 mM). CRH secretion was stimulated by decreasing
      the glucose concentration of the buffer to 1.1 mM. A surge of CRH was released
      over a 2-h period (basal integrated release was 14.4 +/- 1.6 pg/2 h, n = 5 and
      increased to 34.7 +/- 3.1 pg/2 h, n = 14). This response was blocked by mouse
      leptin in a dose-dependent manner (integrated stimulated CRH secretion was 30.6
      +/- 2.5 pg/2 h, n = 5; 20.5 +/- 3.6 pg/2 h, n = 7; 15.3 +/- 4.3 pg/2 h, n = 3 for
      1 nM, 3 nM and 30 nM, respectively). Leptin did not alter secretion of ACTH from
      rat primary cultured pituitary cells. These data demonstrate that leptin can
      inhibit hypothalamic CRH release, either directly or indirectly through another
      hypothalamic neuropeptide such as neuropeptide-Y. Dysfunctional leptin,
      insufficient leptin levels, or leptin resistance should each result in a partial
      open loop, thereby accounting for elevated glucocorticoid levels that accompany
      and contribute to many obese phenotypes. Leptin's ability to inhibit CRH release
      is the likely explanation for its ability to inhibit activation of the HPAA in
      response to stress.

PMID- 9275076
TI  - 24R,25-dihydroxyvitamin D3: an essential vitamin D3 metabolite for both normal
      bone integrity and healing of tibial fracture in chicks.
AB  - We tested the hypothesis that 24R,25-dihydroxyvitamin D3 [24R,25-(OH)2D3] is an
      essential vitamin D metabolite for the development of normal bone integrity and
      the healing of fractures. The natural 24R,25-(OH)2D3 and its synthetic epimer
      24S,25-dihydroxyvitamin D3 [24S,25-(OH)2D3] were tested alone or in combination
      with 1alpha,25-dihydroxyvitamin D3 [1alpha,25-(OH)2D3], on normal bone
      development and other related variables of the Ca2+ homeostasis system [serum
      Ca2+, 25-hydroxyvitamin D3 (25OHD3), 24,25-(OH)2D3, and 1alpha,25-(OH)2D3 levels]
      in chicks. Mechanical testing of torsional strength was carried out on the femur.
      24R,25-(OH)2D3 (80 nmol/kg diet) alone was sufficient for normal bone growth and
      integrity similar to that achieved by the vitamin D3-replete controls. Next,
      chicks were fed a 25OHD3-replete diet (75 nmol/kg diet) for 8 days after
      hatching, and then 25OHD3 was withdrawn to minimize any residual circulating
      metabolites before the imposition of standardized tibial fractures 14 days later.
      Vitamin D metabolites were administered for 2 weeks to determine their effects on
      the mechanical properties of healed tibia. 24S,25-(OH)2D3 combined with 1alpha,25
      (OH)2D3 or 1alpha,25-(OH)2D3 alone resulted in poor healing [strength values of
      0.158 +/- 0.011 and 0.123 +/- 0.009 Nm (Newton x meter), respectively] compared
      with that in the 25OHD3-treated control group (0.374 +/- 0.029 Nm). In contrast,
      the fractured tibia of the birds fed 24R,25-(OH)2D3 in combination with 1alpha,25
      (OH)2D3 showed healing equivalent to that in the control group, with strength
      values of 0.296 +/- 0.043 Nm. These results suggest that when 24R,25-(OH)2D3 is
      present at normal physiological concentrations, it is an essential vitamin D3
      metabolite for both normal bone integrity and healing of fracture in chicks.

PMID- 9275077
TI  - Fetal sheep pituitary proopiomelanocortin in late gestation: effect of bilateral
      lesions of the paraventricular nucleus on regional and cellular messenger
      ribonucleic acid levels.
AB  - Previous experiments have clearly indicated that the successful completion of
      ovine gestation is dependent upon fetal adrenocortical maturation and the
      associated preterm rise in fetal plasma cortisol. The purposes of this study were
      to: 1) examine pituitary POMC messenger RNA (mRNA) levels during normal fetal
      development; and 2) examine the effects of bilateral lesion of the fetal
      paraventricular nucleus (PVN) on levels and spatial distribution of pituitary
      POMC mRNA. Pituitary glands were collected from intact fetal sheep of four
      gestational ages [100-107 days gestational age (dga), n = 8; 117-121 dga, n = 9;
      126-130 dga, n = 9; 144-147 dga, n = 8]. Lesions of the PVN (PVN Lx; n = 4) or
      sham lesions (Sham; n = 5) were performed at 118-122 dga. Pituitary glands from
      PVN Lx and Sham fetuses were collected at 139-142 dga (term approximately 147
      dga). POMC mRNA levels were determined by in situ hybridization. POMC transcript
      levels were determined by both regional analysis (20x magnification) and analysis
      of individual corticotropes (400x magnification). There was no difference among
      gestational age groups in superior anterior pituitary (AP) POMC mRNA levels
      determined by regional or cellular analysis. POMC mRNA levels were significantly
      greater in the inferior AP at 144-147 dga, compared with other gestational ages,
      using regional analysis (P = 0.003) or analysis of individual corticotropes (P <
      0.01). POMC mRNA levels in the neurointermediate lobe in 126- to 130-dga fetuses
      were significantly greater than those in younger fetuses (P = 0.005) but not
      those in 144- to 147-dga fetuses. There was no difference in POMC mRNA levels in
      the superior AP between PVN Lx and Sham, using regional analysis or analysis of
      individual corticotropes. In the inferior AP, there was a significant decrease in
      POMC mRNA levels in PVN Lx, compared with Sham, using both regional analysis (P <
      0.01) and cellular analysis (P < 0.01). There was no difference in POMC mRNA
      levels in the neurointermediate lobe as the result of bilateral PVN Lx. Our
      findings support that basal AP POMC mRNA levels are heterogenously distributed in
      the ovine fetal AP, with POMC mRNA levels in the inferior AP being significantly
      greater than in superior AP, by 144-147 dga. We further found that the higher
      POMC mRNA levels in the inferior AP reflect significantly higher corticotrope
      POMC transcripts and not simply a greater density of corticotropes in this AP
      region. The increase in POMC mRNA levels at 144-147 dga in the inferior AP seems
      unrelated to the onset of adrenocortical maturation (at approximately 125-130
      dga). Finally, we report that increase in corticotrope POMC transcripts during
      late gestation in the inferior AP requires an intact PVN.

PMID- 9275078
TI  - The mouse intraovarian insulin-like growth factor I system: departures from the
      rat paradigm.
AB  - Although the rat intraovarian insulin-like growth factor I (IGF-I) system is well
      documented, the increasing availability of null mouse mutants for components of
      the IGF system necessitates characterization of the mouse model as well.
      Therefore, we undertook to define the components of the mouse intraovarian IGF-I
      system and to examine its operational characteristics. The cellular pattern of
      ovarian gene expression was comparable in the immature rat and mouse for IGF-I
      and the type I IGF receptor. In both species, IGF-I messenger RNA (mRNA) is
      selectively expressed by granulosa cells in growing, healthy appearing follicles.
      Type I IGF receptor mRNA was also concentrated in granulosa cells, but was
      uniformly expressed in all follicles large and small, healthy and atretic
      appearing alike. Cellular patterns of IGF-binding protein (IGFBP) gene expression
      were similar in mouse and rat, except in the case of IGFBP-2. IGFBP-2 mRNA was
      localized to the mouse granulosa cell, in contrast to its concentration in the
      rat thecal-interstitial compartment. This difference in IGFBP expression pattern
      was also noted in cultured mouse and rat granulosa cells. Although immunoreactive
      IGFBP-4 (24 and 28 kDa) and IGFBP-5 (29 kDa) were shared by both species, the
      cultured mouse granulosa cell also featured immunoreactive IGFBP-2 (30 kDa). The
      mouse paradigm further differed from its rat counterpart in that a maximal dose
      of FSH, previously shown to suppress the elaboration of rat granulosa cell
      derived IGFBPs, was without effect. The addition of IGF-I proved stimulatory to
      the accumulation of the 28- to 29-kDa IGFBPs, as previously reported for the rat.
      However, IGF-I proved inhibitory to the accumulation of the 24-kDa IGFBP
      (presumptive nonglycosylated IGFBP-4); no consistent effect was reported for the
      rat model. Functional comparisons of mouse and rat ovarian cell cultures revealed
      qualitatively comparable FSH-stimulated steroidogenesis, disposition of
      radiolabeled pregnenolone, IGF-I-amplified FSH action, and IGFBP-mediated
      antigonadotropic activity. These findings indicate that the mouse intrafollicular
      IGF-I system differs from the rat paradigm in both the makeup and regulation of
      granulosa cell-derived IGFBPs as well as in the intensity and character of the
      steroidogenic process. Studies employing the mouse model must take into account
      these important distinctions relative to the more established rat paradigm.

PMID- 9275079
TI  - The epidermal growth factor receptor is not required for tumor necrosis factor
      alpha action in normal mammary epithelial cells.
AB  - Our laboratory has shown that tumor necrosis factor-alpha (TNF alpha) can
      regulate normal mammary epithelial cell (MEC) growth, morphogenesis, and, under
      certain circumstances, functional differentiation in a manner similar to
      epidermal growth factor (EGF). As TNF alpha has been shown to up-regulate EGF
      receptor (EGFR) expression and function in other systems, the present studies
      were undertaken to determine whether TNF alpha action in MEC was indirect through
      stimulation of the EGFR. An inhibitor of EGFR tyrosine kinase activity, PD158780,
      failed to block proliferation induced by 40 ng/ml TNF alpha and only partially
      inhibited growth in response to 2 ng/ml TNF alpha. PD158780 was also unable to
      suppress the extensive morphological development induced by either TNF alpha
      concentration. In contrast, the effects of TNF alpha and PD158780 on functional
      differentiation (i.e. casein accumulation) were time dependent. When measured on
      day 7 after 48 h of treatment, casein accumulation was unaffected by either
      concentration of TNF alpha or by PD158780. When assessed on day 21 after 16 days
      of treatment, however, casein levels were decreased by 40 ng/ml TNF alpha and
      increased by PD158780. Significantly, this PD158780-induced increase in casein
      was not observed in MEC that had been treated with both PD158780 and TNF alpha.
      These results thus suggest that EGFR tyrosine kinase activity is not necessary
      for TNF alpha action in normal MEC.

PMID- 9275080
TI  - Dissection of the molecular mechanism of action of GW5638, a novel estrogen
      receptor ligand, provides insights into the role of estrogen receptor in bone.
AB  - The estrogen receptor (ER) mixed agonists tamoxifen and raloxifene have been
      shown to protect against bone loss in ovariectomized rats. However, the mechanism
      by which these compounds manifest their activity in bone is unknown. We have used
      a series of in vitro screens to select for compounds that are mechanistically
      distinct from tamoxifen and raloxifene in an effort to define the properties of
      an ER modulator required for bone protection. Using this approach, we identified
      a novel high affinity ER antagonist, GW5638, which when assayed in vitro
      functions as an ER antagonist, inhibiting the agonist activity of estrogen,
      tamoxifen, and raloxifene and reversing the "inverse agonist" activity of the
      pure antiestrogen ICI182,780. Thus, GW5638 appears to function as an antagonist
      in these in vitro systems, although in a manner distinct from other known ER
      modulators. Predictably, therefore, GW5638 alone displays minimal uterotropic
      activity in ovariectomized rats, but will inhibit the agonist activity of
      estradiol in this environment. Unexpectedly, however, this compound functions as
      a full ER agonist in bone and the cardiovascular system. These data suggest that
      the mechanism by which ER operates in different cells is not identical, and that
      classical agonist activity is not required for the bone protective activity of ER
      modulators.

PMID- 9275081
TI  - Human pregnancy serum contains at least two distinct proteolytic activities with
      the ability to degrade insulin-like growth factor binding protein-3.
AB  - The presence of a proteolytic activity in sera from pregnant humans and rodents
      capable of degrading insulin-like growth factor binding protein-3 (IGFBP-3) has
      been known for some time. However, the identity of this activity has remained
      elusive. We have attempted to purify the IGFBP-3 protease activity from pregnant
      human serum (PHS) using the degradation of 125I-IGFBP-3 as a marker. Following
      ammonium sulfate precipitation of PHS and further enrichment of active fractions
      by ion-exchange, protein-A Sepharose, and size-exclusion chromatography, a
      protease of approximately 70-90 kDa was isolated and subjected to N-terminal
      analysis. The N-terminal sequence was consistent with plasminogen, a known
      fibrinolytic enzyme. To further characterize the IGFBP-3 protease activities in
      both PHS and nonpregnant human serum (NHS), aliquots of serum were first enriched
      by polyethylene glycol-precipitation and subjected to size-exclusion
      chromatography. The size-separated fractions were then incubated with 125I-IGFBP
      3, and proteolytic activity was measured. PHS contained two separate proteases
      (>150 kDa and 70-90 kDa), whereas NHS contained only one (70-90 kDa) that had a
      inhibitor profile similar to plasmin. However, inhibitors of plasmin had no
      effect on the activity of the >150-kDa protease. Plasminogen activators (PAs)
      greatly increased the activity of the 70- to 90-kDa protease, but had little
      effect on the >150-kDa protease activity. Addition of PAs greatly increased the
      ability of NHS to proteolyze IGFBP-3. In contrast, the ability of plasminogen
      depleted plasma to degrade 125I-IGFBP-3 was not affected by the addition of PAs.
      Both urokinase and tissue-type PA had the ability to proteolyze IGFBP-3 and were,
      in contrast to the >150-kDa protease activity, inhibited by the specific PA
      inhibitor D-PHE-PRO-ARG chloromethyl ketone. The present data suggest that sera
      has the ability to proteolyze IGFBP-3, and that this ability, as demonstrated by
      NHS, can be regulated by protease inhibitors and PAs. In addition, PHS does
      indeed contain an unique IGFBP-3 protease activity that is not present in NHS,
      and its identity is unknown at this time.

PMID- 9275082
TI  - Parathyroid hormone increases circulating levels of fibronectin in vivo:
      modulating effect of ovariectomy.
AB  - To explore the effect of PTH on circulating levels of fibronectin (FN), adult
      female Sprague-Dawley rats were implanted with Alzet minipumps prepared to
      deliver 7 pmol/h x kg BW of either human PTH (1-34) or human PTH (1-84). Both
      forms of the hormone led to significant and progressive increases in circulating
      levels of FN over the 72-h study period (P < 0.001). However, at every time
      point, circulating levels of FN with human PTH (hPTH) (1-84) infusion were
      significantly higher than with hPTH (1-34), such that at the end of the infusion,
      mean levels in the hPTH (1-34) group were 32.2 +/- 1.4 ng/ml, in the hPTH (1-84)
      group 93.8 +/- 5.4 ng/ml, and in the vehicle infused group 14.6 +/- 0.7 ng/ml.
      The greater agonist efficacy of hPTH (1-84) was not explained by differences in
      circulating levels of the hormones, and both forms of the hormone were equipotent
      at stimulating cAMP production by ROS 17/2.8 cells. However, hPTH (1-84) remained
      a more effective agonist than hPTH (1-34) at stimulating FN production in these
      cells (P < 0.001). Nephrectomy did not blunt the ability of PTH to increase
      circulating FN in vivo, indicating that the kidney was not the source of the FN
      produced in response to PTH. Pretreament with the potent bisphosphonate APD to
      block bone resorption also did not blunt the in vivo response to PTH.
      Parathyroidectomy did not blunt the response. Cultured fetal rat bones showed a
      significant 2.4-fold increase in FN production when treated with PTH. Consistent
      with our earlier in vitro studies (Endocrinology, 135: 1639-1644, 1994), estrogen
      deficiency, induced by ovariectomy, significantly diminished the ability of PTH
      to increase circulating FN levels in vivo (P < 0.001). We conclude that PTH
      increases circulating levels of FN in vivo and may be a physiologic regulator for
      the plasma form of this glycoprotein. The effects of PTH on circulating FN may
      reflect the anabolic properties of the hormone in bone and the blunted response
      following estrogen withdrawal could be a manifestation of the diminished bone
      formation vis-a-vis resorption seen in the estrogen deficient state.

PMID- 9275083
TI  - Adrenal control of erectile function and nitric oxide synthase in the rat penis.
AB  - Penile erection is a nitric oxide (NO)-mediated process that has been shown to be
      androgen dependent in rats. Castration reduces the activity of the penile enzyme
      involved in NO synthesis, nitric oxide synthase (NOS). To determine whether
      adrenal androgens and/or corticosteroids contribute to this control, the
      following groups of Fischer 344 adult male rats (n = 5-7) were studied: 1)
      intact, 2) castrated, 3) adrenalectomized alone, 4) castrated/adrenalectomized,
      5) castrated/adrenalectomized with aldosterone (1.25 mg/kg, s.c.) and
      hydrocortisone (12 mg/kg, s.c.), 6) castrated/adrenalectomized with
      dihydrotestosterone (1.2-cm SILASTIC-brand tubing pellet; Dow Corning, Midland,
      MI), 7) castrated/adrenalectomized with dehydroepiandrosterone (2-cm tubing), 8)
      castrated/adrenalectomized with aldosterone (1.25 mg/kg, s.c.), and 9)
      castrated/adrenalectomized with hydrocortisone (12 mg/kg, s.c.). After 1 week,
      EFS was applied, and the maximal intracavernosal pressure (MIP) and mean arterial
      pressure (MAP) were recorded. The MIP/MAP ratio in the adrenalectomized group
      (0.37) was reduced to values found in the castrated group (0.40). The values in
      both groups were significantly less than those in intact controls (0.75). The
      most significant reduction in MIP/MAP was seen in the adrenalectomized/castrated
      group (0.16). Erectile response in animals submitted to adrenalectomy and
      castration was restored close to intact values with the administration of
      hydrocortisone and aldosterone (0.63). Similar results were obtained by the
      administration of either of the substances alone (0.56 and 0.67, respectively).
      Penile NOS activity assayed by the L-arginine/citrulline conversion was decreased
      by 55% in the castrated group compared with that in the intact group, but was not
      further reduced in the adrenalectomized/castrated or adrenalectomized groups.
      Penile neuronal NOS protein content, estimated by Western blot, was decreased
      only in the adrenalectomized/castrated animals (35%), and endothelial NOS content
      was not affected. These data suggest that the rat adrenal gland contributes to
      the maintenance of the erectile mechanism and may affect neuronal NOS content in
      the penis in the rat model. The possibility that hypotension may play a role in
      the erectile dysfunction observed in adrenalectomized rats cannot be discarded.

PMID- 9275084
TI  - Progesterone, in addition to estrogen, induces cyclin D1 expression in the murine
      mammary epithelial cell, in vivo.
AB  - Previous investigations, in vitro, have demonstrated that progestins can induce
      the transcription of the cell cycle regulator, cyclin D1, thereby suggesting that
      cyclin D1 may mediate, at the molecular level, the proposed mitogenic effects of
      progesterone during mammary epithelial cell proliferation. To extend these
      initial studies into an in vivo context, comparative cyclin D1 Northern and
      immunohistochemical analyses were performed on mammary gland tissue isolated from
      wild type (WT) females as well as from the recently reported progesterone
      receptor knockout (PRKO) mouse model. Northern analysis revealed that estrogen
      induced cyclin D1 expression, 5- to 7-fold over control levels, both in the WT
      and PRKO female. Immunohistochemistry demonstrated that, for both test groups,
      the number of mammary epithelial cells expressing cyclin D1 increased
      significantly as compared with control values, in response to estrogen. In the
      case of estrogen plus progesterone treatment, Northern analysis revealed that, in
      the WT gland, cyclin D1 transcription increased approximately 3-fold over
      estrogen induced levels, an increase that was paralleled by an equivalent
      increase in the number of mammary epithelial cells expressing cyclin D1.
      Conversely, under the same hormone regimen, the PRKO mammary gland did not
      exhibit a further increase in cyclin D1 induction over estrogen only levels.
      Finally, these studies not only demonstrate that in the mammary epithelial cell,
      both estrogen and progesterone can induce the expression of cyclin D1 but also
      show that this induction correlates with mammary gland proliferation in the
      mouse.

PMID- 9275086
TI  - Growth hormone expression in murine bone marrow cells is independent of the
      pituitary transcription factor Pit-1.
AB  - GH has been shown to promote the development and function of leukocytes. The
      expression of both GH and GH-receptors in lymphoid cells has led to the
      hypothesis that GH acts in an autocrine or paracrine fashion. The described
      effects of GH on hematopoiesis and B cell development, led us to investigate GH
      expression in bone marrow cells. By immunocytochemistry, we show that bone marrow
      derived granulocytes and macrophages contain immunoreactive GH. We found that 65
      +/- 24% of the granulocytes were stained with anti-GH, whereas 5.8 +/- 1.5% of
      the granulocytes contained detectable amounts of GH mRNA as assessed by in situ
      hybridization. To address a possible alternative regulation mechanism in bone
      marrow and to establish whether locally derived GH might still play a role in
      pituitary-deficient dwarf mice, we also addressed GH expression in bone marrow
      from hypopituitary Snell dwarf mice. These mice have a mutated gene for the
      pituitary transcription factor Pit-1 that is deficient in DNA binding. Our
      finding that GH expression (immunoreactive protein and mRNA) in bone marrow cells
      from dwarf mice is similar to that in normal mice points to a Pit-1 independent
      regulation of GH in mouse bone marrow.

PMID- 9275085
TI  - Growth hormone and prolactin stimulate the expression of rat preadipocyte factor
      1/delta-like protein in pancreatic islets: molecular cloning and expression
      pattern during development and growth of the endocrine pancreas.
AB  - GH and PRL have been shown to stimulate proliferation and insulin production in
      islets of Langerhans. To identify genes regulated by GH/PRL in islets, we
      performed differential screening of a complementary DNA library from neonatal rat
      islets cultured for 24 h with human GH (hGH). One hGH-induced clone had 96%
      identity with mouse preadipocyte factor-1 (Pref-1, or delta-like protein (Dlk)].
      The size of Pref-1 messenger RNA (mRNA) in islets was 1.6 kilobases, with two
      less abundant mRNAs of 3.7 and 6.2 kilobases. The Pref-1 mRNA content of islets
      from adult rats was only 1% of that in neonatal islets. Pref-1 mRNA was markedly
      up-regulated in islets from pregnant rats from day 12 to term compared with those
      from age-matched female rats. Two peaks in mRNA expression were observed during
      gestation, one on day 14 and the other at term, whereafter it decreased to
      nonpregnant levels. Pref-1 mRNA was up-regulated 3- to 4-fold in neonatal rat
      islets of Langerhans after 48-h culture with hGH, as found also with bovine GH or
      ovine PRL. During the development of pancreas from embryonic day 12 (E12) to
      postnatal day 4, we observed a 2-fold increase in Pref-1 mRNA on E17 and a 5-fold
      increase at birth, followed by a rapid decline on postnatal day 4. Pref-1
      immunoreactivity was found in a subpopulation of insulin cells of neonatal islets
      of Langerhans. At an early embryonal stage (E13), most cells of the pancreatic
      anlage were Pref-1 positive, becoming predominantly restricted to the insulin
      producing cells during development. In conclusion, these findings suggest that
      Pref-1 is involved in both differentiation and growth of beta-cells.

PMID- 9275087
TI  - Gonadotropin-releasing hormone axons target the median eminence: in vitro
      evidence for diffusible chemoattractive signals from the mediobasal hypothalamus.
AB  - The projection of GnRH neurons to the median eminence of the medial basal
      hypothalamus (MBH) is established early in development and is also seen when
      preoptic area-derived GnRH cell-containing grafts are placed in the third
      ventricle of hypogonadal mice. To further study the factors directing GnRH axonal
      targeting, we cultivated embryonic or postnatal day 1 preoptic area with a
      coexplant on collagen- and laminin-coated membranes in insert chambers. After 7
      days of culture, GnRH-immunoreactive fibers extended significantly farther and in
      greater number onto the sector of membrane facing a MBH coexplant than in the
      opposite sector, but not toward coexplants of control tissue. Moreover, such
      effects were specific, as outgrowth of a general axonal population,
      immunoreactive for growth-associated protein 43 was not influenced by the
      presence of the MBH. Preferential GnRH outgrowth toward the MBH was established
      early and was maintained during 10 days of culture. The importance of substrate
      derived guidance was also assessed with confocal microscopy. GnRH axons
      consistently traveled in the company of growth-associated protein 43-labeled
      axons, but only erratic associations were seen between GnRH and glial processes
      extending on the membrane. We suggest that although employing an axonal
      substrate, GnRH axons follow a diffusible chemoattractive signal(s) secreted by
      the MBH.

PMID- 9275088
TI  - Role of prepancreatic (pro)insulin and the insulin receptor in prevention of
      embryonic apoptosis.
AB  - The characterization of (pro)insulin as an early embryonic growth factor requires
      demonstration of its expression and cellular effects in vivo. By in situ
      hybridization, we found widespread preproinsulin transcripts in the chick embryo
      throughout gastrulation and neurulation, before the beginning of preproinsulin
      like growth factor I expression and pancreatic organogenesis. To analyze the
      prepancreatic (pro)insulin effect on apoptotic cell death, we treated embryos
      with antisense oligodeoxynucleotides in ovo and in vitro. The specific effect of
      two preproinsulin messenger RNA (mRNA) antisense oligodeoxynucleotides was
      confirmed by the decrease in a biosynthetically labeled protein
      immunoprecipitated with antiinsulin Igs. Insulin receptor mRNA antisense
      oligodeoxynucleotide applied in ovo increased by 2.7-fold the level of apoptosis
      in the 1.5-day embryo (neurulation) compared with that in its random sequence
      control. In a whole embryo culture, apoptosis increased by 25-35% with the
      addition of preproinsulin or insulin receptor mRNAs antisense
      oligodeoxynucleotides, respectively, whereas it decreased by 64% after 10 h in
      the presence of 10(-8) M chicken insulin. Exogenous insulin also rescued the
      death induced by preproinsulin antisense oligonucleotides. These findings provide
      evidence for an autocrine/paracrine role ofpreproinsulin gene products acting
      through the insulin receptor in the control of cell survival/death during early
      embryonic development.

PMID- 9275089
TI  - Activin is a local regulator of human cytotrophoblast cell differentiation.
AB  - Cytotrophoblast cells of the first trimester placenta are highly invasive when
      removed from villi and cultured in vitro. In vivo, however, only selected
      cytotrophoblast cells break through the overlying syncytiotrophoblast to form
      cytotrophoblast columns and ultimately invade the endometrium. To explore the
      role of paracrine growth factors in regulating cytotrophoblast development, we
      cultured explants of first trimester chorionic villi in vitro. Both activin and
      inhibin, as well as the activin binding protein follistatin, are produced by
      various trophoblast cells throughout pregnancy. We found that addition of activin
      A, but not inhibin-A, stimulated the outgrowth of cytotrophoblast cells into the
      surrounding matrix. This outgrowth was characteristic of that observed in
      extravillous cytotrophoblast cells in vivo; it was accompanied by cell division
      within the proximal region of the cytotrophoblast outgrowth, synthesis of
      fibronectin, as well as the expression of markers characteristic of invasive
      cytotrophoblast cells, human leukocyte antigen-G and matrix metalloproteinase
      (MMP)-9. Activin also specifically induced the early expression of MMP-2 within
      villous cytotrophoblast cells. Addition of the activin binding protein,
      follistatin, blocked all of the effects of exogenous activin. The morphological
      and biochemical effects of activin were similar to those observed when signaling
      of endogenous transforming growth factor-beta was blocked. Interestingly, the
      latter effects were also reversed by the addition of follistatin. These data
      suggest that activin plays a local role in promoting cytotrophoblast column
      formation, likely by regulating the differentiation of villous cytotrophoblast
      into extravillous cytotrophoblast cells.

PMID- 9275090
TI  - The mechanism of excisional fetal wound repair in vitro is responsive to growth
      factors.
AB  - We have investigated the ability of fetal rat skin to heal an excisional wound in
      vitro. Skin from the backs of E17-E19 rats was wounded using a 1-mm diameter
      cutting needle and suspended in culture on a 6-pin cradle for 72 h. Neither
      contraction nor epithelial closure was observed within wounds created in skin
      from E19 embryos. In contrast, wounds in E17 skin contracted to 35-50% of their
      original area over 72 h, although, in the absence of serum, complete wound
      closure was not observed. Addition of FBS at the time of culture resulted in the
      movement of the epithelium over the dermal margins of the wound to effect
      complete closure. Histological sections through these healed wounds revealed an
      epithelial bridge spanning the dermal margins of the wound. A similar mechanism
      of repair was observed in the presence of day 14 adult wound fluid. The response
      of wounds in E17 skin to a range of growth factors was then assessed in an
      attempt to reproduce the serum response under defined conditions. Insulin-like
      growth factor I or epidermal growth factor did not significantly affect wound
      closure. Basic fibroblast growth factor, transforming growth factor-beta, or
      platelet-derived growth factor did promote wound closure although, in contrast to
      the serum-induced response, wound histology revealed repair had been achieved by
      dermal fibroblasts that occupied the space between the epithelial margins of the
      healed wound. We have therefore shown that the epithelial component of fetal
      wound repair proceeds in organ-cultured fetal skin in the absence of an adhesive
      substrate over which to migrate and is dependent on the source of trophic
      factors. The inability of skin taken from the E19 embryo to heal in vitro
      suggests a developmental switch in the mechanism of wound epithelialization.

PMID- 9275091
TI  - Glucose transporter GLUT3 in the rat placental barrier: a possible machinery for
      the transplacental transfer of glucose.
AB  - Glucose transfer across the placental barrier is crucial for fetal development.
      To investigate the role of glucose transporter isoforms in the transplacental
      transfer of glucose, we investigated the localization of glucose transporters
      GLUT1 and GLUT3 immunohistochemically in the rat placenta. In the labyrinth, the
      site of maternofetal exchange of substances, both GLUT1 and GLUT3 were present,
      whereas only GLUT1 was detected in the junctional region. In the labyrinthine
      wall, which lies between maternal and fetal circulations, GLUT3 exhibited
      polarized localization; i.e. it was present at the plasma membranes of the
      maternal blood side in the syncytiotrophoblast layers. GLUT1 was concentrated at
      plasma membranes of the maternal and fetal blood sides of syncytiotrophoblast
      layers. The asymmetric distribution of GLUT3 across the placental barrier may
      suggest asymmetric transfer of glucose, which would be beneficial to provide a
      stable milieu for fetal development.

PMID- 9275092
TI  - Regulation of prostaglandin endoperoxide H synthase 1 and 2 by estradiol and
      progesterone in nonpregnant ovine myometrium and endometrium in vivo.
AB  - PG endoperoxide H synthase-2 (PGHS-2) messenger RNA (mRNA) and protein levels are
      increased dramatically in ovine myometrium and endometrium during both
      glucocorticoid-induced premature labor and spontaneous term labor. In this study,
      we examined estradiol and progesterone regulation in vivo of PGHS-1 and PGHS-2
      expression at both mRNA and protein levels using a nonpregnant ovariectomized
      sheep model. We determined the differential distribution of PGHS-2 and PGHS-1 in
      ovine myometrium and endometrium with immunocytochemistry. Twenty ovariectomized
      ewes were treated with saline (n = 5) or estradiol infused i.v. for 2 days (50
      microg/day; n = 5) or an intravaginal progesterone sponge for 10 days (containing
      0.3 g progesterone; n = 5) or an intravaginal progesterone sponge for 10 days
      with estradiol (50 microg/day) administered on days 9 and 10 with the
      progesterone sponge still in place (EP; n = 5). PGHS-1 and -2 mRNA and protein
      were measured by Northern and Western blot analyses, respectively. PGHS-2 mRNA
      and protein abundance increased significantly in myometrium after estradiol
      treatment (P < 0.01). In contrast, progesterone was a more potent stimulator than
      estradiol of PGHS-2 protein abundance in endometrium (P < 0.01). PGHS-1
      concentration did not change after estradiol and/or progesterone administration
      (P > 0.05). PGHS-2 was immunolocalized in myometrial cells and endometrial
      glandular epithelial cells, whereas immunoreactive PGHS-1 was located in the
      myometrial cells, endothelial and smooth muscle cells of blood vessels, as well
      as epithelial cells of glands and stromal cells in endometrium. Estradiol
      dependent activation of PGHS-2 gene expression resulted in increased PGHS-2
      levels in sheep myometrium in vivo. Progesterone did not have any effect on PGHS
      2 gene expression in the myometrium. In contrast, progesterone was a more potent
      stimulator of endometrial PGHS-2 abundance than estradiol. Estradiol and
      progesterone did not regulate PGHS-1 expression in either endometrium or
      myometrium. The distribution and differential regulation of PGHS-1 and -2 in
      myometrium and endometrium are consistent with the differential functions of both
      enzymes.

PMID- 9275093
TI  - The effects of androgen deficiency on murine bone remodeling and bone mineral
      density are mediated via cells of the osteoblastic lineage.
AB  - Both estrogens and androgens act on bone marrow stromal/osteoblastic cells to
      inhibit the production of local factors that promote osteoclast development.
      Based on this and the evidence that loss of sex steroids up-regulates not only
      osteoclastogenesis but also osteoblastogenesis, we have hypothesized that cells
      of the osteoblastic lineage are the mediators of the adverse effects of sex
      steroid deficiency on bone. To test this hypothesis, we used the senescence
      accelerated mouse (SAMP6), a model of defective osteoblast development, and
      examined the effects of orchidectomy on static and dynamic histological features
      of bone remodeling and on bone mineral density. After orchidectomy in SAMP6 mice,
      the expected increases in osteoblast precursors, cancellous osteoclasts and
      osteoblasts, frequency of remodeling events, trabecular spacing, and rate of bone
      formation were absent or greatly attenuated. Moreover, whereas bone mineral
      density decreased in orchidectomized controls, it did not change in SAMP6. Our
      data indicate that when osteoblast development is defective, orchidectomy fails
      to result in bone loss. This evidence suggests that cells of the osteoblastic
      lineage are essential mediators of the changes in the rate of bone remodeling and
      loss of bone mass that ensue following loss of androgens.

PMID- 9275094
TI  - QSAR models for binding of estrogenic compounds to estrogen receptor alpha and
      beta subtypes.
AB  - We have developed Quantitative Structure-Activity Relationship (QSAR) models
      based on Comparative Molecular Field Analysis (CoMFA) for 31 estrogenic chemicals
      whose relative binding affinity (RBA) is available for both ER-alpha and ER-beta.
      The models demonstrated a significant correlation (r2>0.95) between the CoMFA
      calculated steric/electrostatic fields and corresponding RBA data and a good
      predictive capability (q2>0.6) based on cross-validation. The CoMFA models and
      contour plots obtained for ER-alpha and ER-beta suggest a close similarity
      between the receptors in terms of mode of binding and provide a rational basis
      for ligand selectivity.

PMID- 9275095
TI  - Loss of telomerase activity during male germ cell differentiation.
AB  - Although the activity of telomerase, an enzyme which synthesizes telomeres de
      novo and stabilizes telomere length has been demonstrated in the testis, the
      precise expression of activity in different germ cell types is not known. We
      examined telomerase activity using a PCR-based telomeric repeat amplification
      protocol during development of the rat testis from birth to adulthood. Telomerase
      activity was relatively high from birth to the 4th week of age, and then low
      between the 5th to 10th week, suggesting that the type A spermatogonial stem
      cells may be the population which is expressing the highest levels of telomerase
      activity. To ascertain which germ cells expresses the telomerase activity,
      purified populations of type A spermatogonia from 9-day old rats, and pachytene
      spermatocytes, round spermatids and epididymal spermatozoa from adult rats were
      isolated. While type A spermatogonia expressed very strong telomerase activity,
      the fractions containing pachytene spermatocytes and round spermatids also
      expressed telomerase activity, but at comparatively lower levels. Telomerase
      activity was totally absent in epididymal spermatozoa. Thus, it appears that the
      telomerase activity is expressed at high levels in the type A spermatogonial stem
      cells, is down-regulated during spermatogenesis, and is absent in the
      differentiated spermatozoa.

PMID- 9275097
TI  - Cholecystokinin (CCK) levels are greatly reduced in the brains but not the
      duodenums of Cpe(fat)/Cpe(fat) mice: a regional difference in the involvement of
      carboxypeptidase E (Cpe) in pro-CCK processing.
AB  - In order to assess the possible role of carboxypeptidase E (Cpe) in pro-CCK
      processing, tissues from the Cpe(fat)/Cpe(fat) mice were analyzed for CCK content
      and molecular forms using specific RIAs directed against different portions of
      the prohormone. Levels of amidated CCK were decreased by about 74% in whole brain
      of Cpe(fat)/Cpe(fat) mice in comparison to control mice, while levels of amidated
      CCK in intestine were only reduced by about 36%. In contrast, using an antiserum
      specific for CCK Gly Arg Arg, Cpe(fat)/Cpe(fat) mice brain had about 13-fold
      higher levels of this peptide relative to controls, while levels were identical
      in mutant and control duodenal tissue. This study demonstrates a regional
      difference in the involvement of Cpe in pro-CCK processing. The accumulation of
      CCK Gly Arg Arg in Cpe(fat)/Cpe(fat) brains provides definitive proof that the
      dibasic cleavage of the carboxyl terminus of pro CCK occurs on the carboxyl
      terminal of the dibasic, between the Arg and Ser as well as confirming that
      amidated CCK 8 in brain originates from CCK 8 Gly Arg Arg rather than from larger
      amidated peptides like CCK 22 or CCK 33. The Cpe(fat)/Cpe(fat) mouse phenotype
      obviously involves multiple endocrine defects, however, it is tempting to
      speculate that this severe CNS deficiency in CCK 8 may be related to the adult
      onset obesity seen in this mutant mouse.

PMID- 9275096
TI  - Rapid membrane effects of steroids in neuroblastoma cells: effects of estrogen on
      mitogen activated protein kinase signalling cascade and c-fos immediate early
      gene transcription.
AB  - Rapid effects of steroid hormones have been observed in neuronal cells for many
      years. We show here, that in the human neuroblastoma cell line SK-N-SH, the
      membrane impermeable conjugated 17beta-estradiol (E2BSA) activates mitogen
      activated protein kinase kinase (MAPKK or MEK) and induces the phosphorylation
      and activation of both ERK-1 and ERK-2 (mitogen activated protein kinase or
      MAPK). Additionally, E2BSA induces the transcription of a reporter gene construct
      driven by the promoter of the mouse c-fos proto-oncogene. The effects of this
      membrane impermeable estrogen on c-fos transcription are not inhibited by the
      estrogen receptor antagonists Tamoxifen or ICI 182,780, further excluding the
      involvement of the intracellular estrogen receptor. This is also illustrated by
      the observation that E2BSA does not activate estrogen response element (ERE)
      mediated transcription. This is the first report of rapid membrane effects of
      17beta-estradiol on growth factor related signalling pathways in neuronal cells,
      and indicates a potential mechanism by which 17beta-estradiol might affect the
      expression of genes whose promoters do not contain EREs but are responsive to
      factors acting through other response elements such as AP-1 and SRE sites.

PMID- 9275098
TI  - Low molecular weight components but not dimeric HCG inhibit growth and down
      regulate AP-1 transcription factor in Kaposi's sarcoma cells.
AB  - Kaposi's sarcoma, a sexually dimorphic disease inflicting high mortality in AIDS,
      remains at present without effective treatment. A recent report (Nature 375:64,
      1995) showed that the placental glycoprotein hormone, human chorionic
      gonadotropin (HCG), and surprisingly its beta subunit, inhibit tumorigenicity and
      metastasis of Kaposi's sarcoma cells in mice xenografts. The anti-KS efficacy of
      a commercial HCG was subsequently demonstrated in clinical trials. Experimental
      data presented herein confirm that commercial HCG preparations (known to be about
      25% pure) display significant inhibitory action in a dose-dependent manner.
      However, pure and biologically active HCG has no effect on Kaposi's sarcoma
      growth in culture. In fact, incubation of Kaposi's sarcoma cells with either one
      of four different well characterized preparations of pure HCG dimer or any of its
      two subunits did not alter cellular proliferation suggesting that a contaminant
      (or degradation product) may be the active agent. Commercial HCG preparations
      were subfractionated based on molecular size and each fraction was tested with
      respect to inhibition of KS cell growth, HCG radioreceptor binding and
      steroidogenic bioactivity. Results demonstrate that the anti-KS activity resides
      among low molecular weight components, and not in bona fide (macromolecular) HCG.
      Our study indicates that HCG activity and anti-KS action are separable.
      Interestingly, the active components in the crude HCG markedly down-regulate AP
      1, a complex of transcription factors of the immediate-early response genes
      associated with cell growth. We conclude that, as yet unidentified molecules,
      present in the commercial HCG preparations, are responsible for the growth
      inhibitory effects presumably via the AP-1 signalling pathway.

PMID- 9275099
TI  - Obliterative airway disease after heterotopic tracheal xenotransplantation:
      pathogenesis and prevention using new immunosuppressive agents.
AB  - BACKGROUND: The purpose of this study was to investigate whether obliterative
      bronchiolitis might occur after xenogenic pulmonary transplantation. A model for
      obliterative airway disease (OAD) after tracheal allograft transplantation in the
      rat undergoes tracheal obliteration with histologic features characteristic of
      obliterative bronchiolitis in human lung transplant recipients. Using this model,
      the pathogenesis of OAD and its prevention with immunosuppressive drugs was
      studied in rat recipients of hamster tracheal grafts. METHODS: Tracheae from 30
      hamsters (xenografts) or 23 Brown-Norway rats (allografts) were implanted and
      wrapped in the greater omentum of untreated Lewis rats. The grafts were removed
      on day 1, 3, 7, 14, 21, or 28 after transplantation and stained with hematoxylin
      and eosin and Masson's trichrome and by immunohistochemistry and
      immunofluorescence (IFL) techniques. In addition, 25 recipients were treated with
      cyclosporine (CsA, 10 mg/kg p.o.), leflunomide (LFM, 20 mg/kg p.o.), or rapamycin
      (RPM, 6 mg/kg i.p.) for 14 or 21 days (5 animals per treatment group). Visual and
      morphometric analyses were used to evaluate the extent of airway obliteration,
      luminal coverage by respiratory or flattened cuboidal epithelium, and extent and
      density of peritracheal cellular inflammation. RESULTS: In all xenografts, a
      neutrophilic infiltration of the mucosa and submucosa was observed from day 1
      until day 14 and was associated with complete loss of tracheal epithelium by day
      14. A marked peritracheal mononuclear cellular infiltrate mixed with plasma cells
      and eosinophils was seen on days 7 and 14. Both the extent of peritracheal
      inflammation and the density of the mononuclear cell infiltrate were
      significantly increased in xenograft tracheae when compared with the allografts.
      Tracheal obliteration began on day 14 and reached a maximum of 43% on day 21 with
      evidence of intraluminal fibrosis. In contrast to IFL of allografts, IFL of
      xenografts demonstrated marked deposition of rat immunoglobulin in the
      peritracheal tissue on days 7 and 14. The effects of treatment with
      immunosuppressive drugs on tracheal graft narrowing and protection of respiratory
      epithelium were as follows: After 14 days of treatment, the percentage of
      tracheal graft narrowing was 12%, 23%, and 19% in the no treatment, CsA, and LFM
      groups, respectively; the percentage of respiratory epithelium at 14 days was 0%,
      21%, and 95%. After 21 days of treatment, the percentage of tracheal graft
      narrowing was 43%, 49%, 12%, and 5% for the no treatment, CsA, LFM, and RPM
      groups, respectively; the percentage of respiratory epithelium at 21 days was 0%,
      39%, 86%, and 0%. Using computerized morphometry, the extent and densities of the
      peritracheal cellular infiltrates were significantly reduced in LFM- and CsA
      treated groups when compared with untreated xenograft controls. LFM and RPM, but
      not CsA, significantly reduced the degree of luminal obliteration compared with
      no treatment (P<0.05). LFM and, to a lesser extent, CsA were able to prevent the
      loss of normal respiratory epithelium. Analysis by IFL revealed a marked decrease
      in rat immunoglobulin deposition in xenografts from LFM- and RPM-treated groups
      compared with xenografts from CsA-treated or untreated rats. CONCLUSIONS: (1) OAD
      occurs not only after tracheal allotransplantation but also after
      xenotransplantation. (2) Subepithelial infiltration of neutrophils and the
      appearance of plasma cells and eosinophils in the peritracheal infiltrates
      distinguished the histology of rejected xenografts from allografts. (3) Antibody
      deposition was detected by IFL only in xenografts. (4) Treatment with LFM or RPM
      significantly decreased the severity of luminal obliteration. Importantly, LFM
      also prevented the loss of respiratory epithelium.

PMID- 9275101
TI  - Effect of cytomegalovirus on an experimental model of chronic renal allograft
      rejection under triple-drug treatment in the rat.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection is thought to be a risk factor of
      chronic rejection. In clinical studies and animal models, mainly concerning graft
      vasculopathy, CMV has been demonstrated to enhance allograft arteriosclerosis. In
      this study we have investigated the effect of CMV on the early inflammatory
      response and graft histology in an experimental model of renal transplantation in
      a rat strain combination that develops chronic rejection under triple-drug
      immunosuppression. METHODS: Renal transplantations were performed in a rat strain
      combination of DA-->BN receiving triple-drug treatment (2 mg/kg
      methylprednisolone, 2 mg/kg azathioprine, 5 mg/kg cyclosporine daily
      subcutaneously). One group of immunosuppressed animals was infected with rat CMV,
      the Maastricht strain (10(5) plaque-forming units intraperitoneally), and the
      other group was left uninfected. As a positive control for alloresponse, one
      group of recipients received neither immunosuppression nor virus. Syngenic
      transplantations with triple-drug treatment and CMV were used as negative
      controls. The grafts were monitored by frequent ultrasound-guided fine-needle
      aspiration biopsies, and the intragraft inflammation was quantified in detail by
      the increment method and expressed in corrected increment units (CIU). Graft
      histology was performed in parallel. RESULTS: Nonimmunosuppressed animals
      developed acute rejection with a high peak of inflammation (7.9+/-3.2 CIU), a
      typical blast response, and lymphocytosis followed by infiltration of macrophages
      and necrosis within 7 days. Triple drug-treated animals had a short, mild
      inflammatory response (3.3+/-1.4 CIU at the peak) in the graft 3-5 days after
      transplantation but ended up with histological changes characteristic of chronic
      rejection with vasculopathy and fibrosis 40-60 days later. Triple drug-treated
      animals with CMV demonstrated a significantly stronger inflammation (4.5+/-1.8
      CIU, P<0.01) than those without, and lymphoid activation continued longer and was
      followed by infiltration of macrophages in the graft. CMV infection of the graft
      was demonstrated by viral culture and antigen detection. In histology, chronic
      rejection with intimal thickening of arteries and arterioles and medial necrosis
      of large arteries was seen at 14 days, ending up with remarkable graft fibrosis
      within 20 days after transplantation. CONCLUSION: CMV prolonged and increased
      graft inflammation and accelerated chronic rejection of renal allografts under
      triple-drug treatment.

PMID- 9275100
TI  - Immunopathological observations after xenogeneic liver perfusions using donor
      pigs transgenic for human decay-accelerating factor.
AB  - BACKGROUND: Donor pigs transgenic for human decay-accelerating factor (hDAF) were
      used in a xenogeneic ex vivo liver perfusion model to study the effect of this
      modification on the development of hyperacute rejection. METHODS: Three
      transgenic pigs were hepatectomized after hypothermic portal and transaortal
      gravity perfusion. Livers from six nontransgenic pigs served as controls. All
      livers were perfused for 3 hr with human blood from two donors diluted to a
      hematocrit of 30%. Particular importance was placed on the use of an optimal
      perfusion technique incorporating the floating suspension of the organs in a
      waterbath and intermittent external pressurization. Biochemical, physiological,
      and immunological parameters were assessed. Tissue specimens taken before and
      after perfusion were analyzed using routine histology, electron microscopy, and
      immunohistology. RESULTS: Complement activation was more pronounced in the
      control group. AP50 and CH50 values fell to about 60% of the initial levels in
      control experiments, whereas they remained at 80% of the initial levels during
      perfusion of hDAF livers. After 180 min, pig tumor necrosis factor alpha levels
      were 7862+/-1645 pg/ml for unmodified livers and 2830+/-734 pg/ml in the hDAF
      group. Human tumor necrosis factor alpha levels were similar in both groups.
      Control livers showed marked morphological alterations and distinct deposition of
      complement factors, whereas livers expressing hDAF showed no signs of
      hepatocellular necrosis and almost no complement deposition beyond C3 activation.
      CONCLUSIONS: These results confirm that the transgenic expression of the human
      complement regulatory protein hDAF reduces complement activation and prevents
      hyperacute rejection in a xenogeneic liver perfusion model over the 3-hr
      evaluation period used in this study.

PMID- 9275102
TI  - Influences of dietary omega-3 polyunsaturated fatty acids on the recovery of
      cardiac and renal functions after preservation in hyperlipidemic rats.
AB  - BACKGROUND: The effects of a soybean oil diet and a high-cholesterol oil (HC)
      diet, and an HC diet with eicosapentaenoic acid (EPA) or docosahexaenoic acid
      (DHA) supplementation, on basal and postpreservative cardiac function of the
      hearts and on postpreservative renal function of the kidneys from older rats were
      examined. METHODS: Groups 1 through 4 of 100-week-old rats were fed either
      soybean oil, HC, HC with EPA, or HC with DHA, respectively, for 12 weeks. Blood
      was collected for analysis of plasma fatty acids, and the heart and left kidney
      were removed from the rat. In experiment 1, the heart was perfused on a
      Langendorff apparatus. After evaluation of the cardiac function of each rat, the
      heart was stored in histidine-tryptophan-ketoglutarate solution for 8 hr at 4
      degrees C. The heart was reperfused and the recovery of cardiac function was
      evaluated. The coronary perfusate during reperfusion was collected to measure 6
      keto prostaglandin F1alpha and thromboxane B2. Coronary flow (CF) perfused with
      Krebs-Henseleit bicarbonate (KHB) solution containing 5-hydroxytryptamine (5-HT)
      and nitroglycerin were evaluated in the Langendorff mode with atrial pacing (330
      beats/min). In experiment 2, the excised left kidney was immediately flushed and
      preserved with University of Wisconsin solution for 8 hr at 4 degrees C. The
      kidney was then reperfused with KHB solution and renal function was evaluated.
      RESULTS: The plasma and cardiac EPA levels in group 3 were significantly higher
      than the levels found in the other groups. The plasma and cardiac ratios of EPA
      to arachidonic acid were significantly higher in groups 3 and 4 than in groups 1
      and 2. There were no significant differences in basal cardiac function among any
      of the diet-fed rats. The percentage values of the recovery of aortic flow,
      cardiac output (CO), and left ventricular max dp/dt in group 3 and CO in group 4
      were significantly higher than in group 2. In addition, the recovery of CF in
      group 3 tended to be higher than in group 2 (P=0.07). The percentage values of
      the recovery of aortic flow, CF, CO, and left ventricular max dp/dt in group 1
      were significantly lower than in the other dietary groups. CF reperfused with KHB
      solution containing 5-HT was significantly higher in group 3 than in groups 1 and
      2. CF reperfused with KHB solution containing 5-HT was significantly higher in
      group 4 than in group 1. CF reperfused with KHB solution containing nitroglycerin
      in group 3 tended to be higher than in groups 1 and 2 (P=0.07). The thromboxame
      B2 concentrations in the coronary perfusate during reperfusion in groups 3 and 4
      were significantly lower than in groups 1 and 2. Fractional sodium reabsorption
      in group 3 was significantly higher than in group 2. Inulin clearance in groups 3
      and 4 was significantly higher than in group 1. The postpreservative urinary flow
      in group 3 was significantly higher than in groups 1 and 2. The urinary flow was
      significantly higher in group 4 than in group 1. CONCLUSIONS: These results
      suggest that EPA administration may attenuate preservation and reperfusion injury
      and improve the recovery of cardiac and renal functions in hyperlipidemic and
      older rats. DHA administration may also show beneficial effects on kidney
      preservation in hyperlipidemic rats.

PMID- 9275103
TI  - Serotonin as a useful parameter for cold and warm ischemic injury in small bowel
      transplantation.
AB  - We investigated serotonin as a parameter of cold and warm ischemic injury prior
      to transplantation. Lewis rats were used as both donors and recipients, and the
      proximal 20 cm of jejunum served as the graft. The grafts were preserved in 4
      degrees C lactated Ringer's solution for 0, 6, 12, 18, and 24 hr after harvest
      for cold ischemia (n=7/group). The superior mesenteric artery was clamped for 0,
      15, 30, 60, and 120 min before harvest for warm ischemia (n=7/group). The
      serotonin concentration was measured in the luminal effluent and the preservation
      solution before transplantation, and total serotonin was calculated as the sum of
      these amounts. Finally, transplantation was performed heterotopically. Total
      serotonin increased significantly with both cold and warm ischemic time (P<0.01
      by analysis of variance, Fisher's PLSD); however, between 18 hr and 24 hr of cold
      ischemic time only, there were no significant changes. Total serotonin levels
      correlated well with cold and warm ischemic time, as shown by linear regression
      analysis (cold ischemia: R2=80.2%, P<0.01; warm ischemia: R2=92.8%, P<0.01). We
      established the cutoff level of total serotonin to predict the graft survival at
      2200 ng, and using this critical level, graft survival was predicted by total
      serotonin with a sensitivity of 71.4% and a specificity of 89.8%.
      Immunohistochemical staining with the serotonin antibody revealed that the number
      of serotonin-positive cells decreased with both cold and warm ischemic time. In
      conclusion, serotonin is a useful parameter of cold and warm ischemic injury
      before transplantation and can assist in predicting graft survival.

PMID- 9275104
TI  - Retransplantation of patients with severe posttransplant hepatitis B in the first
      allograft.
AB  - BACKGROUND: The outcome of orthotopic liver transplantation (OLTX) in patients
      retransplanted for severe hepatitis B virus (HBV) in the first allograft has been
      poor due to high rates of HBV reinfection and even more aggressive disease in the
      second graft. Recent data suggest that hepatitis B immunoglobulin (HBIg) given
      after transplantation can be successful in delaying or preventing HBV reinfection
      in patients transplanted for chronic hepatitis B cirrhosis. We report the
      successful retransplantation of patients who developed recurrent or de novo
      hepatitis B after OLTXY. METHODS: Using similar HBIg regimens, two centers
      retransplanted seven patients after they developed recurrent or de novo hepatitis
      B in the first allograft. At retransplantation all seven patients were HBs
      antigen (Ag) positive; four patients were positive for HBeAg and HBV DNA by
      immunoblot assay, two patients were negative for HBeAg and HBV DNA, and one
      patient was positive for HBV DNA and negative for HBeAg. All patients were either
      HDV Ag or anti-HDV negative. One patient was anti-HCV positive. All patients
      received HBIg infusions after retransplantation to maintain serum anti-HBs levels
      >500 IU/L indefinitely. RESULTS: After retransplantation, six of seven patients
      are alive (86%): all are without evidence of HBV recurrence with serum negative
      for HBsAg, HBeAg, and HBV DNA by immunoblot assay. Liver biopsies are normal on
      routine studies with immunohistochemical stains for HBcAg and HBsAg also being
      negative. Mean follow-up of these six patients is 40.1 months (range 21-63
      months). One patient (14%) developed HBV reinfection 7 months after his second
      transplant, in spite of maintaining target anti-HBs levels. He maintained stable
      liver function with minimal evidence of clinical hepatitis B, but died 8 months
      later from an unrelated stroke. CONCLUSIONS: We conclude that patients with
      recurrent or de novo hepatitis B after OLTX can be successfully retransplanted
      using aggressive immunoprophylaxis to prevent HBV reinfection. The failure of
      HBIg therapy in one patient underscores the need for other effective adjunctive
      anti-HBV modalities.

PMID- 9275105
TI  - Successful living related liver transplantation in an adult with fulminant
      hepatic failure.
AB  - We report a case of an adult female who developed fulminant hepatic failure (FHF)
      during the second trimester of pregnancy and underwent a successful living
      related liver transplantation because no cadaveric donor was available during the
      development of life-threatening symptoms. A left lateral segment hepatic graft
      was procured from her brother, whose body weight was similar to hers. Her
      postoperative course was complicated by bleeding at the biliary anastomosis and
      subsequently by a biliary leak. Nevertheless, the complications were corrected
      surgically and the patient recovered well with a good quality of life 5 months
      after the transplant. This case suggests that living related liver
      transplantation should be considered more frequently for adult FHF patients. As
      the window of therapeutic opportunity is narrow for the dramatic condition of
      FHF, wide acceptance of this procedure will be of great benefit for the patients
      suffering from FHF.

PMID- 9275106
TI  - Selection of prognostic factors of acute hepatitis type non-A, non-B for patient
      listing for liver transplantation.
AB  - The aim of this study was to select prognostic factors from information available
      on admission in order to list patients for liver transplantation before the onset
      of hepatic encephalopathy in patients with fatal hepatitis type non-A, non-B.
      Information regarding patient profile and biochemical data obtained on admission
      was analyzed by multiple stepwise logistic regression, and independent prognostic
      factors related to death were selected. Four parameters were selected as
      independent prognostic factors. Patient age (over 50 years), serum total
      bilirubin level (over 10 mg/dl), peripheral leukocyte count, and prothrombin time
      were independently related to death. Positive predictive value, negative
      predictive value, and predictive accuracy were 0.86, 0.79, and 0.84,
      respectively. Our model is able to predict a patient's fatal outcome much earlier
      than other currently used models. It will be helpful for early referral to a
      transplant center.

PMID- 9275108
TI  - Peripheral blood microchimerism in human liver and renal transplant recipients:
      rejection despite donor-specific chimerism.
AB  - BACKGROUND: Development of donor-specific microchimerism (DSM) has been proposed
      as one of the possible mechanisms for induction and maintenance of allograft
      tolerance. The aim of this study was to determine: (1) the state of DSM in liver
      transplant (LTx) and renal transplant (RTx) recipients, (2) whether the
      persistent presence of an allograft is a requirement for maintenance of
      chimerism, and (3) whether donor-specific blood transfusions (DST) facilitate
      chimerism development in RTx recipients and whether this correlates with
      allograft function. METHODS: Qualitative and quantitative analysis of DSM in
      peripheral blood of LTx and RTx recipients was assessed by polymerase chain
      reaction and competitive polymerase chain reaction using HLA-DR probes for
      mismatched antigens between the donor and recipient. RESULTS: LTx recipients (11
      of 12) who had or were having rejection were positive for DSM in circulation
      compared with 4 of 11 with normal allograft function (P<0.01). The number of
      donor cells did not correlate with allograft function. LTx recipients (4 of 4)
      who lost their first allograft and underwent retransplantation retained DSM for
      the first donors. RTx recipients who received DST (8 of 8) were positive for DSM
      compared with 6 of 12 of nontransfused recipients (P<0.045). CONCLUSIONS: The
      results suggest that LTx and RTx recipients undergo rejection despite DSM. The
      development of DSM may not be a prerequisite for normal allograft function. Once
      DSM is established, the presence of the allograft is not required for maintenance
      of chimerism. DST facilitated the development of DSM in RTx recipients. Direct
      correlation was not observed between the development of DSM and allograft
      function in either DST or nontransfused RTx recipients.

PMID- 9275109
TI  - Risks of transplanting kidneys from hepatitis B surface antigen-negative,
      hepatitis B core antibody-positive donors.
AB  - BACKGROUND: As the number of patients on the United States kidney transplant list
      increases, investigation into the utility of transplanting organs formerly
      considered marginal or undesirable has intensified. Using kidneys from hepatitis
      B surface antigen (HBsAg)-positive donors is thought to place recipients at
      excessive risk of graft failure, morbidity, and mortality. However, the risks of
      using kidneys from HBsAg-negative but hepatitis B core antibody (HBcAb)-positive
      donors have not been defined. METHODS: Between 1990 and 1994, our group
      transplanted 1067 cadaveric kidneys, including 38 from HBsAg(-)/HBcAb(+) donors.
      Of these 38 kidneys, 27 were transplanted into HBcAb(-) recipients (group 1) and
      11 were transplanted into HBcAb(+) recipients (group 2). Group 1 and 2 patients
      received no hepatitis immunoglobulin therapy after transplantation and received
      the same immunosuppression and rejection therapies as recipients of kidneys from
      HBcAb(-) donors. RESULTS: After transplantation, none of the group 1 patients
      became HBsAg(+), three became hepatitis B surface antibody (HBsAb)-positive, and
      two became HBcAb(+). Of the group 2 patients, none became newly HBsAg(+) or
      HBsAb(+). No patient receiving a kidney from an HBsAg(-)/HBcAb(+) donor developed
      signs or symptoms of clinical hepatitis B. Graft and patient survival rates were
      similar in both groups and similar to the rates of the 1029 recipients of kidneys
      from HBcAb(-) donors. CONCLUSIONS: Recipients of kidneys from HBsAg(-)/HBcAb(+)
      donors are at a small risk of hepatitis B seroconversion but are at no excess
      risk of graft failure or short-term morbidity or mortality.

PMID- 9275110
TI  - Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the
      prevention of renal allograft rejection: a report of the European Tacrolimus
      Multicenter Renal Study Group.
AB  - BACKGROUND: To confirm the results of a number of studies conducted in Europe,
      the United States, and Japan, this multicenter, randomized trial compared the 12
      month efficacy and safety of tacrolimus- and cyclosporine-based immunosuppressive
      regimens in the prevention of renal allograft rejection. METHODS: A total of 448
      renal transplant recipients were recruited from 15 centers and assigned to
      receive triple-drug therapy consisting of tacrolimus (n=303) or cyclosporine
      (n=145) in conjunction with azathioprine and low-dose corticosteroids. RESULTS:
      At 12 months after transplantation, tacrolimus therapy was associated with a
      significant reduction in the frequency of both acute (tacrolimus 25.9% vs.
      cyclosporine 45.7%; P<0.001 [absolute difference: 19.8%, 95% confidence interval:
      10.0-29.6%]) and corticosteroid-resistant rejection (11.3% vs. 21.6%; P=0.001
      [absolute difference: 10.3%, 95% confidence interval: 2.5-18.2%]). Actuarial 1
      year patient (tacrolimus 93.0% vs. cyclosporine 96.5%; P=0.140) and graft
      survival rates (82.5% vs. 86.2%; P=0.380) did not differ significantly between
      the two treatment groups. Overall, the safety profiles of the tacrolimus- and
      cyclosporine-based regimens were quite comparable. Infections, renal impairment,
      neurological complications, and gastrointestinal complaints were frequently
      reported but were mostly reversible in both groups. Higher incidences of elevated
      serum creatinine, tremor, diarrhea, hyperglycemia, diabetes mellitus, and angina
      pectoris were reported in the tacrolimus treatment group, whereas acne,
      arrhythmia, gingival hyperplasia, and hirsutism were more frequent with
      cyclosporine treatment. CONCLUSIONS: The significant reduction in the incidence
      of episodes of allograft rejection observed with tacrolimus therapy may have
      important long-term implications given the prognostic influence of rejection on
      graft survival.

PMID- 9275107
TI  - Hepatitis C virus genotypes in liver transplant recipients: impact on
      posttransplant recurrence, infections, response to interferon-alpha therapy and
      outcome.
AB  - BACKGROUND: End-stage liver disease due to hepatitis C virus (HCV) is the most
      common indication for liver transplantation in U.S. veterans. We investigated the
      influence of HCV genotypes on the incidence and timing of recurrent HCV
      hepatitis, survival, infectious morbidity, and response to interferon-alpha
      therapy in this unique patient population. METHODS: HCV genotype was determined
      by direct sequencing of the NS5 region of HCV with type-specific primers.
      RESULTS: Genotype 1a (66%, 32/47) was the predominant genotype. Type 1b was found
      in 25% (12/47) of patients and type 2b was found in 9% (4/47).
      Histopathologically recurrent HCV hepatitis developed in 53% (25/47) of the
      patients after transplantation. This group included 45% (14/31) of the patients
      with type 1a, 67% (8/12) of the patients with type 1b, and 25% (1/4) of the
      patients with type 2b (P>0.5). The time to recurrence and the severity of HCV
      recurrence as defined by aminotransferase levels or Knodell scores were not
      different among the three genotypes. There was a trend toward a higher incidence
      of major infections in patients with type 1b (75%) versus type 1a (48%) and type
      2b (50%) (P=0.11). The response to interferon-a therapy did not differ
      significantly among the genotypes. Mortality at 5 years was 16% (5/31) in
      patients with genotype 1a, 42% (5/12) in patients with genotype 1b, and 50% (2/4)
      in patients with genotype 2b (P=0.06). CONCLUSIONS: The incidence, time to
      recurrence, and response to interferon-alpha therapy did not differ between the
      various genotypes in our liver transplant recipients. However, there was a trend
      toward higher infectious morbidity and overall mortality in patients with
      genotype 1b after transplantation.

PMID- 9275111
TI  - Renal graft rejection or urinary tract infection? The value of myeloperoxidase, C
      reactive protein, and alpha2-macroglobulin in the urine.
AB  - Previous investigations have shown that the determination of two acute-phase
      proteins in the urine, C-reactive protein (CRPu) and alpha2-macroglobulin (alpha2
      MGu), allows a noninvasive diagnosis of acute renal graft dysfunction. A reliable
      differentiation between rejection and urinary tract infection can be made only
      when considering the C-reactive protein in serum and urine at the same time
      (CRPs:CRPu ratio). Therefore, a diagnostic procedure independent of parameters
      other than urinary proteins is needed. As granulocytes play only a minor role in
      graft rejection but are a common feature in urinary tract infection, we
      determined a marker of granulocytes (myeloperoxidase) in urine (MPOu). Eighty
      nine renal transplant recipients were included in the study. In normal courses,
      CRPu, alpha2-MGu, and MPOu were within the normal range. In 15 cases of acute
      interstitial rejection, an increased excretion of CRPu and alpha2-MGu could be
      confirmed, but MPOu could not be detected. On the occasion of acute vascular
      rejection (n=6), with the exception of one case, MPOu could not be observed. The
      pattern of the three urinary proteins differed in urinary tract infections
      (n=40): MPOu could be detected in all cases, CRPu in 50% of cases, and alpha2-MGu
      in 73% of cases. In patients with cytomegalovirus infection (n=7), no MPOu, CRPu,
      or alpha2-MGu was found. In conclusion, the simultaneous measurement of the three
      proteins allows a complete, noninvasive, differential diagnostic procedure of
      renal graft dysfunction.

PMID- 9275112
TI  - Quantitation of the changes in splenic architecture during the rejection of
      cardiac allografts or xenografts.
AB  - BACKGROUND: The spleen plays a central role in the generation of both cellular
      and antibody responses during graft rejection. Although changes in lymphocyte
      function have been extensively analyzed in vitro, there have been limited
      attempts at quantitating the structural changes in the lymphoid compartments
      within the spleen during graft rejection. METHODS: We describe here a means of
      quantitating the histological changes in the spleen using immunohistochemical
      techniques and computerized image analysis. RESULTS: Allograft rejection at 6
      days after transplant is characterized by a threefold increase in the T cell-rich
      areas of the periarteriolar lymphoid sheaths (PALs). The follicular areas are
      enlarged and germinal centers appear in 55% of the white pulp regions. Acute
      xenograft rejection, 4 days after transplant, is specifically accompanied by a
      2.3-fold increase in the marginal zone (MZ) and an increase in the numbers of B
      cells in the red pulp of the spleen. The expansion of both PALs and
      follicular/germinal centers during xenograft rejection is comparable to that
      observed during allograft rejection. We also investigated the effect of two
      immunosuppressants, leflunomide and cyclosporine, on the spleen of rats with
      hamster hearts. Leflunomide, which prevents acute xenograft rejection, prevented
      the increase in PALs and significantly reduced the areas comprising the MZ and
      follicles. Cyclosporine, which does not alter the tempo of xenograft rejection
      and only partially inhibited xenospecific antibody production, inhibited the
      increase in PALs and the appearance of germinal centers, while permitting a
      modest increase in the area of MZ and follicles. CONCLUSIONS: These observations
      collectively suggest that both T cell-dependent and T cell-independent responses
      are stimulated by the transplanted xenograft. However, the T cell-independent
      responses that initiate xenograft rejection are characterized by very modest
      increases in the area of MZ and follicles within the white pulp of the spleen.

PMID- 9275113
TI  - Differences in dermal analogs influence subsequent pigmentation, epidermal
      differentiation, basement membrane, and rete ridge formation of transplanted
      composite skin grafts.
AB  - This study evaluated the in vitro and in vivo function of composite skin
      equivalents based on two different dermal analogs. Keratinocytes derived from the
      same dark-skinned neonatal foreskins were seeded onto both acellular human dermis
      and fibroblast-contracted collagen gels. Each type of composite graft readily
      formed an epithelium in vitro. However, the undulating surface of the acellular
      dermis acted as a template and organized the seeded keratinocytes into a rete
      ridge-like pattern, whereas the smooth surface of the fibroblast-contracted
      collagen gels generated an epithelium with a linear basal layer. Moreover, when
      acellular dermis was used, the composite grafts demonstrated enhanced melanocyte
      proliferation. When transplanted to athymic mice, both composite grafts formed a
      fully differentiated human epidermis, but repigmentation of the grafts when
      acellular dermis was used was more extensive and only the epidermis on the
      fibroblast-contracted collagen gels showed signs of hyperproliferation at 6 weeks
      after grafting. These results demonstrate that the type of dermal analog
      incorporated into a composite skin graft can influence the subsequent
      functionality of the skin substitute.

PMID- 9275114
TI  - Immunohistochemical characterization of inflammatory and proliferative events
      during chronic rejection in rat lung allografts.
AB  - BACKGROUND: Chronic rejection is assumed to be the principle cause of airway
      injury leading to obliterative bronchiolitis (OB) after lung transplantation
      (Tx). To better understand the contribution of chronic rejection in the
      development of OB in allografted lungs, we examined the histopathological changes
      and cytokine expression in inadequately immunosuppressed rat lung allografts.
      METHODS: Three groups of rats were studied: group I, control nontransplanted
      Lewis (Lew) rats (n=5); group II, syngeneic Lew-to-Lew isografts (n=25); and
      group III, Brown Norway-to-Lew allografts (n=25). Groups II and III received two
      single doses of cyclosporine on postoperative days 2-3. Transplanted animals were
      killed (n=5) at monthly intervals from 2 months to 6 months after Tx. Resected
      lungs were stained with hematoxylin and eosin, Masson's trichrome, and Van
      Gieson's elastin, and immunostained with antisera to interleukin (IL)-1beta, IL
      8, and basic fibroblast growth factor (bFGF). The intensity of immunostaining was
      graded from 0 to 4 (0=no staining, 4=strong staining). RESULTS: In groups I and
      II, normal airways and vessels were observed. Minimal intensity and distribution
      of immunostaining for all markers were detected in groups I and II. Group III
      allografts demonstrated acute grade II-III vascular rejection with mild
      bronchiolar injury and inflammation at 2 months after Tx. At 6 months after Tx,
      all allografts demonstrated severe and diffuse chronic vascular rejection. Late
      airway changes consistent with OB were detected in four of five allografts,
      however, these lesions were expressed infrequently. Immunohistochemical findings
      revealed moderate to strong expression for IL-8 and bFGF over the airway
      epithelium, acute and chronic inflammatory cells, and fibroblasts in allografts
      at 2 months after Tx. Despite focal development of OB at 6 months, intensity and
      distribution of immunostaining significantly decreased for all three cytokine
      markers. CONCLUSIONS: Inadequate immunosuppression of rat lung allografts leads
      primarily to chronic vascular rejection but fails to induce severe and diffuse
      development of OB. In this animal model, cytokines IL-1beta, IL-8, and bFGF are
      likely to play an important role in the early inflammatory phase but not during
      the late proliferative events of chronic rejection.

PMID- 9275115
TI  - Optimizing a limiting dilution culture system for quantifying the frequency of
      interleukin-2-producing alloreactive T helper lymphocytes.
AB  - BACKGROUND: The development of sensitive, specific, and reproducible techniques
      to quantify T cells with direct allospecificity has potential applications in the
      selection of bone marrow donors and in the monitoring of the antidonor
      alloresponse in patients after organ transplantation. Such data may provide an
      objective basis for altering existing immunosuppression, monitoring novel
      antirejection therapies, and predicting long-term graft outcome. We have
      previously published a correlation between donor antirecipient T helper
      frequencies (HTLf) and the severity of acute graft-versus-host disease after bone
      marrow transplantation. Using the same assay protocol, we have described the
      development of donor-specific hyporesponsiveness in a proportion of renal
      transplant recipients. However, several imperfections existed in the protocols
      used in these studies. Cellular interactions within the stimulator and the
      responder cell populations, and back stimulation of T cells within the stimulator
      cell population, could give rise to extraneous interleukin-2 and alter the
      validity or estimation of derived recipient antidonor HTLf. METHODS: Using
      peripheral blood mononuclear cells as the responding population and splenic
      mononuclear cells as the stimulating population, we have examined the possible
      effects of these cellular interactions on the results of limiting dilution
      analysis assays for HTLf measurement. RESULTS: These interactions have the
      ability to alter the validity or estimation of HTLf. We show that by depleting
      the responder population of HLA class II+ cells and depleting T cells from the
      stimulating population, these interactions are effectively abrogated.
      CONCLUSIONS: On the basis of the findings reported here, we describe an optimized
      HTLf assay which is sensitive, specific, and reproducible. This has obvious
      applications in the analysis of alloimmune responses in transplantation.

PMID- 9275116
TI  - Co-culture of pancreatic islets and allogeneic lymphocytes: alterations of
      responder and stimulator cells.
AB  - Mixed lymphocyte cultures have been used, e.g., in clinical transplantation, for
      donor-recipient selections. In experimental research, the mixed lymphocyte
      culture is valuable in studying several aspects of lymphocyte activation by
      allogeneic major histocompatibility complex (MHC) antigens and, therefore, in
      proving new strategies of interrupting lymphocyte activation and proliferation.
      However, this in vitro model is donor-specific but not antigen-specific.
      Therefore, we used islets of Langerhans, the donor tissue for grafting diabetic
      recipients, to stimulate allogeneic mononuclear cells prepared from spleens of
      healthy LEW.1A, LEW.1W, or WF rats and from diabetes-prone normoglycemic BB/OK
      rats. The considerable advantage of the mixed lymphocyte islet culture is not
      only the antigen specificity but also the possibility to separate lymphocytes
      from islets after the co-culture. In addition to lymphocyte activation, we
      investigated cytokine secretion and changes of antigen expression on the
      stimulatory islet cells. After allogeneic co-culture, lymphocyte activation was
      found by an increased release of the cytokines interferon-gamma, interleukin 2,
      and macrophage inflammatory protein 2, as well as by an enhanced expression of
      the interleukin 2 receptor on CD4+ T and CD8+ T cells. We also demonstrated
      changes in antigen expression on the surface of stimulatory islet cells after co
      culture with allogeneic lymphocytes. These changes comprised not only the
      enhancement of MHC class I and intercellular adhesion molecule 1 but also the
      induction of MHC class II antigens on pancreatic beta cells. Activation of
      responding lymphocytes, cytokine secretion, and changes in islet cell antigen
      expression were time dependent. We did not find major differences in the effects
      induced by allogeneic lymphocytes obtained from the different donor rat strains.
      In a syngeneic control mixed lymphocyte islet culture, lymphocytes were not
      activated and no induction of MHC class II antigens on beta cells was observed.
      However, up-regulation of intercellular adhesion molecule 1 was found. The
      enhancement and induction of MHC antigens and an adhesion molecule improve the
      binding of effector and target cells supporting our hypothesis that the change of
      antigen expression on target cells induced by allogeneic lymphocytes might
      contribute to their destruction. Since lymphocytes obtained from healthy or
      diabetes-prone rats induce very similar effects, we conclude that the results
      described are of general importance.

PMID- 9275117
TI  - Resistance to monoclonal antibody-induced CD8+ T-cell depletion in thymectomized
      MHC class II-deficient mice.
AB  - BACKGROUND: CD8+ T cells are present at higher than normal levels in MHC class II
      deficient (IIKO) mice. METHODS: In this study, we have examined the sensitivity
      of CD8+ T cells to depletion induced by a single injection or multiple injections
      of an anti-CD8 monoclonal antibody (mAb) (2.43) in IIKO mice in vivo. RESULTS:
      Thymectomized (ATX) IIKO mice showed the presence of a greater percentage of
      memory CD8+ T cells (CD44high, CD45RBlow, and MEL-14(-)) in peripheral blood
      lymphocytes (PBL) by 1 month after ATX compared with age-matched euthymic mice.
      Although CD8+ cells were not detectable in the periphery at 5 and 14 days after
      2.43 injection, CD8+ T cell receptor alpha/beta+ cells expressing the memory
      phenotype had recovered markedly by 21 days after mAb injection in these ATX IIKO
      mice. The expression of CD8 beta-chain and Thy-1 as well as the absence of CD4
      and of T cell receptor gamma/delta among most recovering CD8+ cells, and their
      varied Vbeta usage, suggested that these cells were derived from the thymus
      rather than from extra-thymic T-cell differentiation or from oligoclonal
      peripheral expansion. In addition, low numbers of CD8+ cells that were coated
      with mAb (2.43) were detected in the lymph nodes of ATX IIKO mice 7 days after
      mAb injection. Most of these nondepleted lymph node CD8+ cells expressed the
      memory phenotype and low levels of CD8beta. Furthermore, the levels of recovering
      CD8+ cells in PBL of ATX IIKO mice by 21 days after mAb treatment were markedly
      higher than those in PBL of simultaneously mAb-treated ATX wild-type (B10) mice.
      CONCLUSION: Together, these studies indicate that memory CD8+ T cells are
      relatively resistant to mAb-induced depletion in vivo.

PMID- 9275118
TI  - Down-regulation of Gal alpha(1,3)Gal expression by alpha1,2-fucosyltransferase:
      further characterization of alpha1,2-fucosyltransferase transgenic mice.
AB  - BACKGROUND: In pig-to-primate transplantation, antibody-mediated hyperacute
      rejection is the consequence of binding of natural antibodies to Gal
      alpha(1,3)Gal on pig endothelium. The elimination of the Gal alpha(1,3)Gal
      antigen from pig cells should prevent hyperacute rejection. Using in vitro
      techniques, we have previously reported that using the alpha1,2
      fucosyltransferase gene induces the preferential expression of H substance with a
      concomitant reduction in the expression of Gal alpha(1,3)Gal. The aim of the
      present study was to examine the effect of expressing the alpha1,2
      fucosyltransferase gene in vivo on Gal alpha(1,3)Gal. METHODS: Three alpha1,2
      fucosyltransferase transgenic lines of mice were produced and characterized
      serologically and histologically. RESULTS: Immunohistological studies showed
      heavy staining for H substance in liver, spleen, kidney, and heart, with a
      reduction in staining for Gal alpha(1,3)Gal. In addition, there was a reduction
      in the binding of human anti-Gal alpha(1,3)Gal antibody to lymphocytes from
      alpha1,2-fucosyltransferase transgenic mice and a substantial decrease in
      complement-mediated cytolysis of alpha1,2-fucosyltransferase transgenic
      lymphocytes when compared with that obtained with normal mice. CONCLUSIONS: The
      findings have important implications, in that alpha1,2-fucosyltransferase
      transgenic pigs could be produced as a source for humans. Such pigs should have a
      reduced expression of Gal alpha(1,3)Gal.

PMID- 9275119
TI  - Heterogeneity of human anti-pig natural antibodies cross-reactive with the
      Gal(alpha1,3)Galactose epitope.
AB  - BACKGROUND: The cell surface carbohydrate moiety, Gal(alpha1,3)Galactose
      (alphaGal), has been implicated as the major determinant recognized by more than
      80% of human anti-porcine natural antibodies (NAb). An ELISA system was developed
      for the detection of this subpopulation of porcine cell-reactive NAb using
      synthetic alphaGal conjugated to bovine serum albumin. METHODS: A screen of 95
      human serum samples by this method demonstrated marked variability in the
      alphaGal reactivity of unrelated donors. The percentage of alphaGal-reactive NAb
      relative to total immunoglobulin was determined for 10 donors. RESULTS: alphaGal
      reactive NAb comprised 1.0-2.4% of total serum IgG, whereas the range was from
      3.9% to 8.0% for IgM. CONCLUSIONS: The higher level of alphaGal-reactive IgM
      suggests that xenoreactive NAbs may be the product of germ-line genes. Two
      dimensional gel analysis of affinity-purified alphaGal-reactive NAb from two
      donors provided evidence suggesting that IgM from this subpopulation of NAb were
      restricted in protein charge heterogeneity.

PMID- 9275120
TI  - Fractionation of feline bone marrow with the soybean agglutinin lectin yields
      populations enriched for erythroid and myeloid elements: transplantation of
      soybean agglutinin-negative cells into lethally irradiated recipients.
AB  - Feline bone marrow cells treated with the soybean agglutinin (SBA) lectin are
      separated into two populations, the agglutinated SBA(+) fraction containing
      predominantly cells of myeloid origin and the nonagglutinated SBA(-) fraction
      consisting of cells primarily of the erythroid lineage. FACScan analyses revealed
      a clear distinction of the cells based on their light scattering properties,
      i.e., large cells and cells with high granularity were found in the SBA(+)
      fraction, whereas cells having a low forward light scatter and side light scatter
      were found in the SBA(-) fraction. Colony-forming assays showed colony-forming
      unit-granulocyte/monocyte (CFU-GM) cells to have a strong affinity for SBA
      because these were found almost entirely in the SBA(+) fraction; in contrast,
      burst-forming unit-erythroid (BFU-E)-forming cells were concentrated in the SBA(
      ) fraction. When the marrow was fractionated by counterflow centrifugal
      elutriation (CCE), a differential binding to SBA among the CFU-GM forming cells
      was found. The SBA(-) fractions of cells collected at 21 and 25 ml/min contained
      primarily BFU-E forming cells, similar to that observed with whole marrow; the
      later CCE fractions, those collected at 32 ml/min and the rotor off fraction,
      when treated with SBA showed a small but significant number of CFU-GM cells in
      the SBA(-) fraction. T lymphocytes were found predominantly in the SBA(+)
      fractions of whole bone marrow and the CCE fractions. Successful autologous
      marrow transplants were performed with the early CCE SBA(-) fractions. The latter
      cells were used for our initial transplant attempts because ongoing studies in
      our laboratory had shown these cells to be free of any viral-containing cells
      when the marrow had been obtained from animals infected with the feline
      immunodeficiency virus. In summary, although SBA treatment of feline marrow
      yields a marked separation of CFU-GM and BFU-E progenitors, select CCE SBA(-)
      fractions contain stem cells capable of providing hematopoietic reconstitution of
      lethally irradiated animals.

PMID- 9275121
TI  - Increased expression of tissue cytokines in graft-versus-host disease after small
      bowel transplantation in the rat.
AB  - BACKGROUND: Graft-versus-host disease (GVHD) occurs in the recipient after small
      bowel transplantation (SBT). Proinflammatory cytokines, such as tumor necrosis
      factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin 6 (IL-6),
      may be important mediators of GVHD. Increased expression of these cytokines might
      precede the clinical manifestations of GVHD induced by SBT. METHODS: Heterotopic
      SBT was performed using Lewis donors into Lewis x Brown Norway F1 (LBN-F1)
      recipients. The isograft control was performed from LBN-F1 into LBN-F1. Animals
      were killed on the 5th and 11th postoperative day (POD). mRNA was isolated from
      recipient native small bowel, colon, spleen, liver, and mesenteric lymph nodes
      and from nonsurgical controls as baseline. Semiquantitative reverse transcriptase
      polymerase chain reaction was performed to amplify mRNA transcripts for TNF
      alpha, IFN-gamma, and IL-6 using alpha32P-dATP incorporation. Clinical signs,
      histologic assessment, and cytokine expression were correlated. RESULTS: On POD
      5, there were neither clinical signs nor histologic features of GVHD, but mRNA
      expression of TNF-alpha and IL-6 in small bowel, IL-6 in spleen, and IFN-gamma in
      mesenteric lymph nodes were significantly increased in allograft animals when
      compared with normal and isograft tissues. On POD 11, both the clinical signs and
      histologic features of GVHD were seen, and TNF-alpha and IL-6 in native small
      bowel, TNF-alpha in colon, IFN-gamma in spleen, and IL-6 in mesenteric lymph
      nodes were significantly increased in allograft animals when compared with that
      in normal and isograft tissues. CONCLUSIONS: In conclusion, TNF-alpha, IFN-gamma,
      and IL-6 expression precede clinical onset and histologic evidence of GVHD in
      specific tissues. Therefore, increased expression of these cytokines is
      correlated with the development of GVHD in this model of SBT.

PMID- 9275122
TI  - Prolongation of murine vascularized heart allograft survival by recipient
      specific anti-major histocompatibility complex class II antibody.
AB  - BACKGROUND: Antibodies targeting recipient major histocompatibility complex (MHC)
      class II molecules have been demonstrated to be effective at prolonging allograft
      survival. However, antigen-presenting cell depletion would explain this effect
      and has not been definitively excluded as the mechanism of action of such
      antibodies. We have studied an anti-MHC class II antibody (OX6) proven to be
      noncytotoxic in the recipient strain used. METHODS: Antibody was administered the
      day before, 2 hr before, and the day after grafting. RESULTS: Antibody
      administration on the day before, 2 hr before, and the day after grafting
      significantly prolonged vascularized cardiac allograft survival. Importantly,
      treatment recognizing recipient MHC was effective, whereas a similar regimen
      recognizing donor MHC was not. CONCLUSIONS: Noncytotoxic recipient MHC class II
      specific antibodies modify allograft rejection. Possible mechanisms for this
      therapeutic effect are discussed.

PMID- 9275123
TI  - Incidence of adenomatous colorectal polyps in cardiac transplant recipients.
AB  - BACKGROUND: The present study evaluates the effects of long-term
      immunosuppression after cardiac transplantation on the risk for adenomatous
      polyps. METHODS: The endoscopic procedures performed at LDS and University
      Hospitals in cardiac transplant recipients were reviewed and compared with
      results from a previously studied control group. RESULTS: A total of 123
      endoscopic procedures were performed in 98 heart transplant patients (59% for
      cancer screening and 41% for gastrointestinal complaints). Eighty-five percent of
      patients were male and 15% were female; their mean age was 57 years. In the group
      <3 years posttransplant, adenomatous polyps were present in 25%, hyperplastic
      polyps were present in 10%, and synchronous lesions in 3 patients. In the group
      >3 years posttransplant, adenomatous polyps were present in 16%, hyperplastic
      polyps were present in 22%, and synchronous lesions in were evident in 3
      patients. No significant difference with results from a previously studied
      control group. CONCLUSIONS: Long-term immunosuppression does not increase the
      risk for adenomatous polyps of the colon.

PMID- 9275124
TI  - Human leukocyte antigen sensitization after cryopreserved human meniscal
      transplantations.
AB  - The presence of antibodies against human leukocyte antigens (HLA) in recipients
      of cryopreserved, non-tissue-antigen-matched human meniscal allografts was
      evaluated. Serological HLA typing was performed for both class I and class II
      antigens. The results showed that 11 of 18 recipients became sensitized.

PMID- 9275125
TI  - Salvage therapy with mycophenolate mofetil for lung transplant bronchiolitis
      obliterans: importance of dosage.
AB  - BACKGROUND: Bronchiolitis obliterans (BO) is the most important long-term
      complication of lung transplantation. Treatment of this condition is often
      unsuccessful. METHODS: A patient presented with early BO. Despite OKT3 and the
      addition of methotrexate, the patient needed persistently high doses of
      prednisone to maintain lung function at a moderate level. Only the substitution
      of azathioprine by mycophenolate mofetil (MMF, 3 g/day) made it possible to
      reduce the dose of prednisone. RESULTS: Reduction of the dose of MMF to 2 g/day
      resulted in a deterioration of lung function, which improved impressively after
      MMF was increased again to 3 g/day. CONCLUSIONS: MMF may be a valuable therapy
      for lung transplant BO. However, the use of a high dose, i.e., 3 g/day, may be
      crucial.

PMID- 9275126
TI  - A simple method to confirm patency of the graft bile duct during living-related
      partial liver transplantation.
AB  - A bile duct stricture caused by an inadvertent ligation or suture during donor
      operation is rare, but not a negligible complication after living-related liver
      transplantation (LRLT). We present here a simple technique to prevent this kind
      of complication. Before bilioenteric anastomosis, a rod-shaped surgical probe was
      introduced into the bile ducts of the graft to examine their patency. The
      position of the surgical probe and the liver segment in which the probe proceeded
      was checked using ultrasonography. Using this technique in all of our 60 cases of
      LRLT, we have had no experience of this bile duct complication. We recommend this
      technique to be adopted in LRLT and split-liver transplantation to diminish the
      risk of biliary complications.

PMID- 9275127
TI  - Prevalence of hepatitis G virus infection in kidney transplant recipients.
AB  - BACKGROUND: We investigated the prevalence, risk factors, and consequences of
      hepatitis G virus (HGV) infection in 87 kidney transplant recipients. METHODS:
      Infection was diagnosed with reverse transcriptase polymerase chain reaction
      using primers in the NS3 region of the viral genoma. RESULTS: Twenty-four
      patients (27.5%) were HGV RNA positive (HGV+ group) and 63 patients (72.5%) were
      HGV RNA negative (HGV- group). No statistically significant differences were
      found between the two groups for age, sex, transplantation and hemodialysis
      duration, number of kidney transplantations, serum creatinine, history of
      transfusions, hepatitis B and C virus infections, and percentage of patients
      having suffered from acute rejection. Acute and chronic hepatitis were not more
      prevalent in the HGV+ group than in the HGV- group. CONCLUSIONS: HGV infection is
      highly prevalent in kidney transplant recipients but does not alter liver or
      kidney functions. HGV contamination may be linked to nosocomial transmission
      during long-term hemodialysis.

PMID- 9275129
TI  - Ex vivo adenovirus-mediated gene delivery leads to long-term expression in
      pancreatic islet transplants.
AB  - BACKGROUND: Replication-deficient adenovirus, one of the most efficient vectors
      in gene therapy, has been limited by transient transgene expression due to its
      episomal location and loss during cell division, as well as a host immune
      response against viral proteins. METHODS: Murine pancreatic islets were infected
      ex vivo with ad5-cytomegalovirus (CMV)-beta-galactosidase and transplanted into
      diabetic recipients with normalization of glucose metabolism. RESULTS: High
      levels of beta-galactosidase activity were detectable histologically for at least
      20 weeks after transplant, and beta-galactosidase and viral mRNA were also
      present that long. Sera from transplanted animals did not significantly inhibit
      ad5-CMV-interleukin-2-Ig infection of HeLa cells in vitro, whereas sera from
      intravenously delivered ad5-CMV-beta-galactosidase drastically diminished HeLa
      cell infection, suggesting the presence of reduced levels of antibodies in
      transplanted animals as compared with intravenously infected animals.
      Immunofluorescent staining of islet isografts infected with ad5-CMV-beta
      galactosidase revealed the presence of CD8+ and CD4+ T lymphocytes at all time
      points, however, no islet destruction was seen. CONCLUSIONS: Treatment of islet
      isografts ex vivo with ad5-CMV-beta-galactosidase results in prolonged transgene
      expression, possibly due to an attenuated immune response against adenovirus.

PMID- 9275128
TI  - Quality of life after kidney transplantation in children.
AB  - We assessed the long-term rehabilitation and quality of life after kidney
      transplantation in 17 recipients of transplants during their childhood who had
      reached 10 years or more after grafting. We found that all recipients considered
      themselves to be in good to excellent health, and 59% were completely satisfied
      with their life. Ninety-four percent of the recipients did not report any
      interference of their health with their family life. Only one recipient was
      unemployed, and five recipients have to miss work (n=2) and school (n=3) a few
      days a year due to their health status. Health seldom or never interfered with
      social life in 11 recipients, and in 6 of 9 sexually active recipients, their
      health status was not an obstacle in their sexual relationships. Two recipients
      expressed concerns about their short stature, and three were concerned with their
      body appearance. In conclusion, we describe a group of young adult recipients who
      presented a highly satisfactory rehabilitation and quality of life after their
      successful transplantation.

PMID- 9275130
TI  - Relationship between ABO blood group and levels of Gal alpha,3Galactose-reactive
      human immunoglobulin G.
AB  - BACKGROUND: The terminal Gal alpha1,3Galactose (alphaGal) determinant is present
      on all porcine glycoproteins and glycolipids, but is not expressed by human
      cells. Consequently human sera contain anti-alphaGal natural antibodies. The
      human blood group B antigen [Gal alpha1,3(Fuc1,2)Galactose] is differentiated
      from the alphaGal epitope by the presence of a fucosyl group. METHODS: To
      determine whether the expression of the B antigen has any effect on the level of
      alphaGal-reactive natural antibodies, equal numbers (n=12) of A, B, AB, and O
      serum samples were evaluated by ELISA and flow cytometry. RESULTS: A significant
      reduction in IgG alphaGal reactivity was observed with serum samples from B
      antigen-expressing donors (B, AB) relative to non-B antigen-expressing donors (A,
      O). CONCLUSIONS: These results are consistent with the possibility that anti
      alphaGal antibodies in non-B antigen-expressing individuals include a subset that
      is reactive with the structurally related B antigen and that this subset is
      absent in B and AB individuals.

PMID- 9275131
TI  - Severe hemolytic anemia due to anti-E after renal transplantation.

PMID- 9275132
TI  - Viruses in asthma.

PMID- 9275133
TI  - Mechanisms of action of intravenous immune serum globulin in autoimmune and
      inflammatory diseases.
AB  - Intravenous immune serum globulin (IVIG) is primarily used as replacement therapy
      in patients with hypogammaglobulinemia. It has been over 15 years since IVIG was
      first shown to be effective in the treatment of patients with autoimmune
      thrombocytopenic purpura. Over the past decade, IVIG has been used in the
      treatment of a number of autoimmune and systemic inflammatory disorders. Although
      the use of IVIG in many of these immune-mediated disorders was purely speculative
      initially, we now have a much better understanding of the mechanisms by which
      IVIG exerts its effects in these autoimmune diseases. IVIG exhibits a number of
      immune modulatory activities that are mediated by the Fc portion of IgG through
      the Fc gamma receptor on a variety of cell types. Although the major component in
      IVIG is IgG, other minor components such as solubilized lymphocyte surface
      membrane determinants and specific antibodies to lymphocyte surface molecules may
      have important immunoregulatory effects on T- and B-cell immune responses. This
      review discusses the proposed mechanisms of action of IVIG in autoimmune and
      inflammatory disorders.

PMID- 9275134
TI  - Olfactory dysfunction in allergic rhinitis is related to nasal eosinophilic
      inflammation.
AB  - BACKGROUND: Olfactory dysfunction is a common finding in patients suffering from
      allergic rhinitis. However, little is known about the pathophysiology underlying
      this phenomenon and about the time course of hyposmia in seasonal allergy.
      METHODS: A prospective controlled study was performed on 17 patients with
      allergic rhinitis to grass pollen in order to evaluate olfactory function in
      correlation to the duration of allergen exposition, symptoms, eosinophil cationic
      protein (ECP) in nasal secretions, and nasal volume flow (NVF). Olfactory
      function was evaluated preseasonally and on days 3, 7, 14, and 21 of the season
      using a modified Connecticut Chemosensory Clinical Research Center testing
      procedure for threshold, identification, and discrimination. Twelve volunteers
      without allergy served as controls. RESULTS: Preseasonally, patients and controls
      performed equally in discrimination and identification testing, but not in
      threshold testing. No changes were found in the controls, but a significant
      decrease in threshold and identification from the 7th day of the season in
      patients with allergy was noted that was better correlated to ECP than to NVF.
      NVF was already maximally decreased from the 3rd intraseasonal day with no
      further changes. ECP increase became significant at day 14. CONCLUSION: Patients
      with grass pollen allergy develop olfactory dysfunction during natural allergen
      exposure that might be related to allergic inflammatory mechanisms.

PMID- 9275135
TI  - Nebulized salbutamol with and without ipratropium bromide in the treatment of
      acute asthma.
AB  - BACKGROUND: Routine addition of ipratropium bromide to beta-agonist therapy in
      acute asthma is of uncertain benefit. OBJECTIVE: This study was carried out to
      evaluate: (1) whether nebulized ipratropium (0.5 mg) plus salbutamol (2.5 mg)
      (Combivent) confers additional bronchodilation over nebulized salbutamol (2.5 mg)
      alone in patients with acute asthma and (2) whether adjustment for prognostic
      indicators of outcome influences any benefit seen with ipratropium. METHODS: A
      double-blind, two-center, randomized, single-dose study was performed in 338
      patients with asthma, aged 18 to 55 years, who attended the emergency department
      for treatment of acute asthma. The primary end point was FEV1 at 90 minutes.
      RESULTS: The mean absolute difference in FEV1 at 90 minutes for Combivent
      compared with salbutamol was 113 ml (SEM +/- 48 ml, p < 0.05). Independent of the
      study drug received, a poor response to treatment was predicted by frequent use
      of inhaled beta-agonist before presentation (p < 0.0001), severity of the attack
      (p < 0.05), and longer duration of attack (p < 0.05). Subjects who had taken more
      than 10 puffs of inhaled beta-agonist through a metered-dose inhaler or who had
      serum salbutamol levels of greater than 2 mmol/L on presentation demonstrated no
      benefit from the addition of ipratropium. Patients with an FEV1 less than 1 L on
      presentation also responded less well to Combivent, which was explained by the
      association between severity of attack and greater use of inhaled beta-agonist
      therapy. CONCLUSION: A single dose of nebulized Combivent confers additional
      bronchodilation over salbutamol alone (p < 0.05) in acute asthma. Patients who
      exhibited most benefit from the addition of ipratropium were those who had
      consumed the least inhaled beta-agonist before presentation, not those with the
      most severe asthma.

PMID- 9275136
TI  - Allergenic activity of heated and ovomucoid-depleted egg white.
AB  - BACKGROUND: No egg white products have been clearly proven to be hypoallergenic.
      The role of egg white proteins in allergic reactions to eggs is still debatable.
      OBJECTIVE: This study was designed to determine the importance of ovomucoid, an
      egg white protein, in the development of allergies to egg white. METHODS: We
      performed a double-blind, placebo-controlled food challenge in subjects with high
      levels of IgE antibodies for egg white to compare the allergenicities of heated
      and ovomucoid-depleted egg white, freeze-dried egg white, and heated egg white.
      Levels of IgE antibodies for egg white, ovomucoid, ovalbumin, ovotransferrin, and
      lysozyme were measured in serum by RAST. RESULTS: Twenty-one of 38 subjects with
      positive challenge responses to freeze-dried egg white had negative challenge
      responses to heated egg white, whereas 16 of 17 subjects (94.1%) with positive
      responses to heated egg white did not respond to the heated and ovomucoid
      depleted egg white challenge. The subjects with positive challenge responses to
      freeze-dried egg white tended to have higher IgE antibody values to ovomucoid
      than those with negative responses. IgE antibody levels to ovomucoid were
      significantly higher in subjects with positive responses to a challenge with
      heated egg white than in those with no response. There were no significant
      differences in the levels of IgE antibodies to the other proteins, except
      ovomucoid, in the negative-response and positive-response groups in challenge
      tests with freeze-dried and heated egg white. CONCLUSION: The heated and
      ovomucoid-depleted egg white preparation was less allergenic than heated or
      freeze-dried preparations. Ovomucoid has a more important role in the
      pathogenesis of allergic reactions to egg white than other proteins in egg white.

PMID- 9275137
TI  - Exposure to indoor allergens in early infancy and sensitization.
AB  - BACKGROUND: Indoor allergens play a major role both in sensitization and as
      triggers of asthma in children. The relationship between allergen exposure and
      sensitization to cats, dogs, and mites was studied prospectively in 100 newborn
      babies with a history of allergy in both parents. METHODS: Skin prick tests were
      done with Dermatophagoides pteronyssinus, D.farinae, and cat and dog allergens in
      all the children at 6 and 18 months of age and in 86 children at 5 years of age.
      Dust samples were collected from the homes during infancy and at 5 years. The
      parents of the children responded to a questionnaire focused on environmental
      factors that could influence indoor allergen levels. In addition, dust samples
      were collected from the day-care centers of the sensitized children. The allergen
      levels were determined by ELISA. RESULTS: The levels of the major cat allergen,
      Fel d 1, varied from 0.02 microg to 6.8 microg/gm (geometric mean [GM], 0.4
      microg/gm) during infancy and less than 0.02 microg to 13 microg/gm dust (GM,
      0.12 microg/gm) at age 5 years. Dog allergen, Can f 1, levels ranged from 0.18
      microg to 590 microg/gm (GM, 3.1 microg/gm) in infancy and 0.09 microg to 13
      microg/gm at age 5 years (GM, 0.6 microg/gm). Eleven children (13%) were
      sensitive to cats, and three were sensitive to dogs at 5 years of age. They had
      been exposed to similar levels of allergen as the nonsensitized children. The
      levels of mite allergen (Der p 1 + Der f 1) at age 1 year varied from less than
      0.02 microg to 1 microg/gm dust (GM, 0.12 microg/gm) and at age 5 years from less
      than 0.02 microg to 3.5 microg/gm (GM, 0.05 microg/gm) dust. Only two homes
      contained mite allergen levels greater than 2 microg/gm dust. The levels were
      less than 0.3 microg/gm dust in all but one sample from the day-care centers.
      Only one child was sensitized to mites at age 5 years. The mite allergen level
      was less than 0.1 microg/gm at home, and he did not attend a day-care center.
      CONCLUSIONS: The findings indicate that exposure to low levels of indoor
      allergens in early childhood is associated with a low incidence of sensitization.
      However, levels well below currently suggested threshold levels may cause
      sensitization in children with a family history of allergy. We suggest that a
      fixed threshold risk level for allergic sensitization may not be appropriate in
      all climates.

PMID- 9275138
TI  - Timing of venom skin tests and IgE determinations after insect sting anaphylaxis.

PMID- 9275139
TI  - Chronic sinusitis: risk factors for extensive disease.
AB  - BACKGROUND: Chronic sinus disease is one of the most common diseases in the
      United States, and little is understood about its pathogenesis. OBJECTIVE: To
      characterize prospectively the immunologic parameters that accompany extensive
      chronic sinusitis. METHODS: Eighty adult patients with chronic sinus symptoms had
      a complete blood count with differential, coronal computed tomographic (CT) scan
      of the sinuses, and serum assays for total IgE, specific IgE, IgA, IgG, IgG
      subclasses, and pneumococcal titers. RESULTS: Thirty-seven (46%) patients had
      extensive sinusitis, defined as a CT score > or = 12. A highly significant
      correlation was noted between the extent of disease and the peripheral eosinophil
      count (r = 0.53, p < 0.0001). In keeping with this finding, an eosinophil count >
      or = 200/microl was strongly associated with extensive disease (odds ratio [OR] =
      19.2, 95% confidence interval [CI] = 5.4 to 72.7). Asthma (OR = 6.8, 95% CI = 2.2
      to 22.0), atopy (OR = 4.3, 95% CI, 1.5 to 12.8), and age > or = 50 years (OR =
      6.5, 95% CI = 2.0 to 22.2) were also associated with extensive disease. However,
      the association of eosinophils with extent of disease was independent of asthma,
      atopy, or age. Levels of IgG1, IgG2, and IgG3 subclasses did not correlate with
      extent of disease seen on CT scan. Although total IgE and IgG4 levels did
      correlate with disease, on multiple stepwise regression they did not add to the
      predictive value of the eosinophil count in identifying patients with extensive
      disease. CONCLUSIONS: The association of asthma, atopy, eosinophilia, and
      elevated levels of IgE and IgG4 with extensive disease on CT scan is compatible
      with the hypothesis that chronic sinusitis may be a disease of immune activation
      of the T(H2) type.

PMID- 9275140
TI  - Cross-reactivity of skin and serum specific IgE responses and allergen analysis
      for three mosquito species with worldwide distribution.
AB  - BACKGROUND: Allergic reactions to mosquito bites are a common problem worldwide.
      Cross-reactive immunologic responses have not been reported. OBJECTIVE: For the
      three most common mosquito species, Aedes (Ae.) vexans, Ae. aegypti, and Culex
      (Cx.) quinquefaciatus, we investigated skin and serum specific IgE responses and
      analyzed salivary allergens. METHODS: Locally, Ae. vexans is a major pest, but
      Ae. aegypti and Cx. quinquefaciatus are not found. We studied 41 subjects living
      in Manitoba, using (1) skin bite tests, (2) ELISA to measure serum mosquito
      saliva- or salivary gland-specific IgE, (3) ELISA inhibition tests, and (4)
      sodium dodecylsulfate-polyacrylamide gel electrophoresis and immunoblotting.
      RESULTS: Twenty-nine of the 41 subjects had skin reactions to Ae. vexans bites.
      Twenty-two of the 29 also reacted to Ae. aegypti bites. Mean serum mosquito-IgE
      levels to each of the three species were significantly higher in the reactive
      subjects than in the nonreactive subjects. Significant intercorrelations were
      found among skin reactions and mosquito-specific IgE levels for the three
      species. The Ae. aegypti-IgE ELISA reaction could be inhibited by addition of
      each mosquito extract. The serum IgE and IgG from Manitobans reacted with the
      antigens of all three species. A 37 kd allergen in each of the three species was
      recognized by the antibody against a recombinant Ae. aegypti saliva protein.
      CONCLUSIONS: Strong cross-reactive skin and IgE responses and species-shared
      antigens exist among the three mosquito species studied.

PMID- 9275141
TI  - Quantitative bronchial challenge tests with wheat flour dust administered by
      spinhaler: comparison with aqueous wheat flour extract inhalation.
AB  - BACKGROUND: Quantitative bronchial challenge tests with flour dust for the
      diagnosis of bakers' asthma may be performed by inhalation of flour delivered to
      the patient's respiratory tract by sophisticated equipment. OBJECTIVE: This study
      was carried out to assess the diagnostic value of bronchial challenge tests with
      flour dust inhalation from capsules administered by a Spinhaler (Fisons Inc.,
      Loughborough, U.K.) and to compare this method quantitatively with bronchial
      challenge tests with a commercially available wheat flour extract. METHODS: A
      highly selected group of 36 bakers with work-related symptoms of rhinitis or
      asthma were referred to our department, a tertiary referral center, from 1992 to
      1995. Thirty-four of the subjects and 10 atopic control subjects were included in
      this study. After the assessment of bronchial hyperresponsiveness on day 1,
      subjects were randomized to inhale an aqueous wheat flour extract at
      concentrations of 0.01, 0.1, 1, 10, and 100 mg/ml by tidal volume breathing for
      10 minutes or to inhale wheat flour dust filled in capsules on days 2 and 3. One,
      two, and four capsules (maximum of 7 cumulative capsules) of flour dust were
      administered by a Spinhaler. In addition, skin prick tests were performed with a
      battery of environmental and occupational allergens. Total serum IgE and specific
      IgE to wheat flour were measured by standard procedures. RESULTS: Seventeen
      bakers and two control subjects demonstrated a positive skin test response to
      wheat flour (wheal > or = 3 mm). Fifteen bakers demonstrated a fall of 50% or
      more in specific airway conductance after inhalation of the commercial wheat
      flour extract, and 11 demonstrated such a fall in specific airway conductance
      after inhalation of wheat dust. Three control subjects had a positive bronchial
      challenge response to the extract, but dust inhalation from the capsule did not
      cause positive bronchial reactions in control subjects. When a 50% fall of
      specific airway conductance was used as criterion for a positive bronchial
      provocation test result, sensitivity for the extract or dust inhalation was 0.44
      and 0.32, respectively, and specificity was 0.7 and 1.0, respectively. If only
      subjects with a positive skin test response to wheat flour were considered,
      sensitivity of both tests was 0.65. With more stringent criteria for the gold
      standard, there was a trend for a higher sensitivity but a lower specificity of
      the extract inhalation. Both methods were safe. CONCLUSION: The validity of
      bronchial challenge tests with wheat flour dust inhaled from Spinhaler capsules
      was superior to that of tests done with a commercially available aqueous wheat
      flour extract. The higher specificity of the Spinhaler method might be an
      advantage if bronchial challenge tests are used as confirmation tests.

PMID- 9275142
TI  - Dexamethasone inhibits prolonged survival and autocrine granulocyte-macrophage
      colony-stimulating factor production by human eosinophils cultured on laminin or
      tissue fibronectin.
AB  - BACKGROUND: Eosinophil autocrine generation of viability-promoting cytokines
      resulting from interaction with extracellular matrix (ECM) proteins may be
      important in promoting their persistence in allergic inflammation. OBJECTIVE: We
      examined eosinophil interaction with fibronectin, laminin, collagen, fibrinogen,
      hyaluronate, or vitronectin in terms of adhesion and for their ability to promote
      prolonged eosinophil survival by autocrine generation of IL-3, IL-5, or
      granulocyte-macrophage colony-stimulating factor (GM-CSF). The effect of
      dexamethasone was examined because it may inhibit integrin-dependent autocrine
      generation of viability-enhancing cytokines. METHODS: Microtiter wells were
      coated with different ECM proteins, and assays were performed to determine their
      levels of eosinophil adhesion, and tests were performed to determine their
      prolonged survival in culture. The receptors involved in these processes, the
      cytokines generated, and the effect of a dose range of dexamethasone were all
      examined. RESULTS: Eosinophils cultured for 3 days on laminin or tissue
      fibronectin exhibited dose-dependent prolonged survival, which was not seen with
      any other ECM protein. Unstimulated eosinophils adhered to wells coated with
      laminin or fibronectin but not to wells coated with any of the other ECM proteins
      that were tested. Laminin-dependent eosinophil adhesion and prolonged survival
      were inhibited by specific monoclonal antibodies to beta1 and alpha6beta1.
      Laminin-dependent survival was inhibited by a neutralizing antibody to GM-CSF, an
      anti-IL-5 antibody achieved a measurable but insignificant inhibition of
      survival, and an antibody to IL-3 had no effect. Increasing concentrations of
      dexamethasone (maximal at 10(-7) mol/L) inhibited both laminin- and fibronectin
      dependent enhanced eosinophil viability at 3 days. Eosinophils cultured on either
      laminin or fibronectin for 24 or 72 hours generated picogram quantities of GM
      CSF, which were inhibited by the addition of dexamethasone (10(-7) mol/L).
      CONCLUSION: We have confirmed that eosinophils adhere to laminin in an
      alpha6beta1-dependent manner, and this interaction results in the autocrine
      generation of GM-CSF, which enhances eosinophil survival in culture. Both laminin
      and tissue fibronectin-dependent autocrine GM-CSF generation were inhibited by
      physiologically relevant concentrations of dexamethasone. This may represent an
      important mechanism by which glucocorticoids reduce the tissue eosinophilia in
      allergic disease.

PMID- 9275143
TI  - Eosinophil cationic protein and histamine after intestinal challenge in patients
      with cow's milk intolerance.
AB  - BACKGROUND: Mast cells and eosinophils are key cells in the development of active
      symptoms in allergic diseases and other inflammatory conditions, and they mediate
      their action through the release of very potent granule constituents. METHODS:
      Five patients with milk-related gastrointestinal symptoms diagnosed by double
      blind placebo-controlled milk challenges, but with negative responses to skin
      prick tests and RASTs with milk, and eight healthy control subjects were
      investigated. Repeated perfusion studies were performed with a two-balloon, six
      channel tube by using milk, casein, and whey as antigens. Luminal eosinophil
      cationic protein, histamine, and albumin were measured by radioimmunoassay.
      RESULTS: Luminal cow's milk induced a pronounced increase in intestinal secretion
      of histamine and eosinophil cationic protein in patients, but not control
      subjects, during the first 20 minutes after challenge (histamine from 123 +/- 12
      to 543 +/- 175 ng/cm, hr; eosinophil cationic protein from 80 +/- 23 to 686 +/-
      262 ng/cm, hr). Albumin, as a marker of plasma leakage, was also significantly
      increased. CONCLUSION: These data indicate that mast cells and eosinophils are
      effector cells not only in patients with allergic disease but also in patients
      intolerant to foods and lacking circulating antibodies. The underlying mechanisms
      may be a reaction mediated by locally appearing antibodies or an immunologic
      activation resembling that found in intestinal disorders such as celiac disease.

PMID- 9275144
TI  - Characterization of the allergens of the house dust mite Euroglyphus maynei.
AB  - BACKGROUND: The house dust mite Euroglyphus maynei inhabits homes in many parts
      of the world and is the source of many allergens. OBJECTIVE: The purpose of this
      study was to biochemically and immunologically characterize the major allergens
      of E. maynei. METHODS: Proteins in an extract of E. maynei were separated into 20
      fractions by using preparative isoelectric focusing. Most proteins and allergens
      were contained in fractions 7 to 17 with pH of 4.8 to 8.0. The fractions were
      further characterized by nonreducing sodium dodecylsulfate-polyacrylamide gel
      electrophoresis and immunoblotting with the serum of 16 individuals sensitive to
      E. maynei. RESULTS: Molecular weights and isoelectric points were assigned to 47
      IgE-binding proteins in an E. maynei extract, and the frequency of IgE binding to
      each allergen was determined. Twenty-two of the allergens were recognized by more
      than 50% of the 16 sera, and all but one of the subjects had IgE that bound to
      more than 10 allergens (range, 0 to 32). One of the proteins was identified as
      the allergen Eur m 2. CONCLUSION: E. maynei is the source of at least 47
      individual allergens that have been characterized by molecular weight,
      isoelectric point, and IgE-binding properties.

PMID- 9275145
TI  - Quantification of the major brown shrimp allergen Pen a 1 (tropomyosin) by a
      monoclonal antibody-based sandwich ELISA.
AB  - BACKGROUND: Among 13 allergens found in extracts of cooked brown shrimp (Penaeus
      aztecus) the 36 kd muscle protein tropomyosin has been identified as the only
      major shrimp allergen (Pen a 1). Cross-reacting molecules with similar molecular
      weights were detected in other crustacea species such as crab, lobster, and
      crawfish. Because Pen a 1 and Pen a 1-like allergens are important in crustacea
      allergy, the aim of this study was to develop a monoclonal antibody (mAb)-based
      sandwich ELISA to quantify Pen a 1 and to evaluate Pen a 1 levels in four
      commercial shrimp, crab, and lobster extracts. METHODS: Two Pen a 1-specific mAbs
      with different epitope specificities were selected. ELISA plates coated with
      captured mAb 3.2 were incubated with samples containing Pen a 1. Bound Pen a 1
      was detected by a combination of biotinylated mAb 4.9.5 and alkaline phosphatase
      labeled streptavidin. RESULTS: The optimized sandwich ELISA could detect Pen a 1
      concentrations ranging from 4 to 125 ng/ml. Four commercial shrimp extracts
      demonstrated a 40-fold difference in Pen a 1 levels (24 to 920 microg/ml). Crab
      and lobster extracts contained detectable levels of Pen a 1-like proteins. No
      reactivity to cockroach, house dust mite, oyster, codfish, or peanut extracts was
      detected, which indicates that the developed assay is crustacea-specific.
      CONCLUSION: A sensitive sandwich assay was developed to quantify Pen a 1. This
      assay will be helpful to standardize shrimp extracts in regard to the content of
      the major allergen, Pen a 1, and to study cross-reactivities among and evaluate
      occupational exposure to different crustacea species.

PMID- 9275146
TI  - Endocytosis, storage, and release of IgE by human platelets: differences in
      patients with type I allergy and nonatopic subjects.
AB  - Platelets of atopic individuals differ in alpha-granular contents and in the
      amount of biologically active mediators released compared with platelets of
      nonatopic subjects. Because platelets carry the low-affinity IgE receptor (CD23),
      they may contribute to long-lasting IgE sensitivity by serving as a storage pool
      for IgE. We compared 45 atopic individuals with immediate-type allergies and 25
      nonatopic control subjects with respect to storage and release of IgE by their
      platelets. Platelets of atopic individuals were characterized by a 10-fold higher
      median IgE content compared with those of nonatopic control subjects. The
      platelet IgE content correlated with the serum IgE level in the four atopic
      individuals with seasonal allergies who were followed up monthly over 1 year.
      Platelet stimulation with platelet activating factor, but not with thrombin or
      adenosine diphosphate, resulted in a release of 65% of the stored IgE.
      Conversely, platelet stimulation with monoclonal IgE/kappa resulted in the
      release of the chemokine RANTES. Platelet alpha-granules were identified as the
      main storage compartment for IgE by postembedding immunocytochemistry. Although
      more than half of the alpha-granules showed gold labeling for IgE, additional
      labeling was found on the external face of the plasma membrane and within the
      open canalicular system, indicating endocytosis and exocytosis of IgE. Moreover,
      the detection of CD23 not only on the plasma membrane but also on membranes of
      the alpha-granules further supports the existence of an exchange of IgE between
      the blood plasma and an internal storage compartment. Endocytosis could be
      confirmed by the uptake of an IgE myeloma protein coupled to colloidal gold. We
      conclude that platelets of atopic individuals may contribute to allergic
      inflammation by serving as a storage pool for IgE and by their increased capacity
      to liberate further mediators of allergy in response to IgE stimulation.

PMID- 9275147
TI  - Antibody to very late activation antigen 4 prevents interleukin-5-induced airway
      hyperresponsiveness and eosinophil infiltration in the airways of guinea pigs.
AB  - This study examines the effect of monoclonal antibody to very late activation
      antigen-4 (VLA-4) on IL5-induced airway hyperresponsiveness in vivo and
      eosinophil accumulation into guinea pig airways. IL5 has been shown to be
      important in the development of airway hyperresponsiveness and eosinophil
      accumulation in the guinea pig. Eosinophils, unlike neutrophils, express VLA-4
      which mediates the adhesion to vascular cell adhesion molecule-1 on endothelial
      cells. Thus VLA-4 seems to be an important adhesion molecule in the infiltration
      of eosinophils from the vasculature into the airway tissue. In addition, it has
      been shown that IL5 activates VLA-4 on eosinophils to facilitate their adhesion.
      In the present study, IL5 (1 microg, twice on one day) or vehicle were
      administered intranasally. Monoclonal antibody (mAb) to VLA-4 (HP1/2) or the
      isotype-matched control mAb (1E6) were injected 1 hour before each IL5 or vehicle
      treatment at a dose of 2.5 mg/kg body weight. The next day in vivo bronchial
      reactivity, eosinophil number in bronchoalveolar lavage (BAL) fluid, and
      eosinophil peroxidase (EPO) activity in cell-free BAL fluid were determined. IL5
      induces an increase in bronchial reactivity to histamine, which is associated
      with an accumulation of eosinophils into BAL fluid (control: 12 (5 to 42) x 10(5)
      cells and IL5: 69 (11 to 99) x 10(5) cells, p < 0.05) and an increase of 35% +/-
      14% in EPO activity in cell-free BAL fluid. Intravenous administration of anti
      VLA-4 mAb, but not of the control antibody, completely inhibits the bronchial
      hyperresponsiveness as well as the airway eosinophilia found after intraairway
      application of IL5. HP1/2 also suppresses the IL5-induced increase in EPO
      activity in cell-free BAL fluid. In conclusion, for the development of IL5
      induced airway hyperresponsiveness in the guinea pig, the VLA-4-dependent
      infiltration and activation of eosinophils in the bronchial tissue seems to be
      essential.

PMID- 9275148
TI  - BDA20, a major bovine dander allergen characterized at the sequence level, is Bos
      d 2.

PMID- 9275149
TI  - Generation of anaphylatoxins through proteolytic processing of C3 and C5 by house
      dust mite protease.
AB  - BACKGROUND: The group 3 allergen of Dermatophagoides species (Der p 3 and Der f
      3) has been identified as a 30 kd trypsin-like protease of the house dust mite.
      We previously showed that the 30 kd protease from Dermatophagoides farinae (Df
      protease) could activate the bradykinin-generating cascade and exacerbate
      inflammatory reactions. OBJECTIVE: The purpose of this study was to determine
      whether Df-protease could enzymatically generate anaphylatoxins from complement
      components C3 and C5. METHODS: Df-protease was incubated with human serum C3 or
      C5 in a purified system, and the anaphylatoxin activity produced was assayed by
      measuring enhancement of vascular permeability and release of histamine from mast
      cells triggered by C3a and by assessing chemotaxis of polymorphonuclear cells
      caused by C5a. We also attempted to determine whether protease isolated from
      house dust could cause release of C5a from C5. RESULTS: Df-protease showed strong
      activation of C3 and C5, producing C3a and C5a by proteolytic cleavage of the
      complements. An appreciable amount of Df-protease was recovered in the house dust
      extract, and the house dust protease caused C5a release from C5. CONCLUSION: Df
      protease activated the complement system to produce anaphylatoxins. Thus it is
      suggested that house dust mite proteases may contribute to the pathogenesis of
      allergic and inflammatory diseases caused by house dust allergens.

PMID- 9275150
TI  - The glutamine 27 beta2-adrenoceptor polymorphism is associated with elevated IgE
      levels in asthmatic families.
AB  - BACKGROUND: The beta2-adrenoceptor polymorphisms occurring at amino acid
      positions 16 (arginine to glycine) and 27 (glutamine to glutamate) are known to
      be functionally relevant and also disease-modifying in subjects with asthma.
      However, the contribution of these polymorphisms to the development of the
      asthmatic phenotype or other markers for allergic disease remains to be
      established. OBJECTIVE: This large family study examines the contributions of
      these polymorphisms in determining the heritable component of markers for
      allergic disease in asthmatic families. METHODS: Three hundred twenty-four
      individuals from 60 families multiplex for asthma selected by means of an
      asthmatic proband were characterized for the following markers of allergic
      disease: asthma, atopy, and serum IgE. The polymerase chain reaction was used to
      generate a 234 base pair fragment spanning the region of interest, and the beta2
      adrenoceptor polymorphism was then defined by allele-specific oligonucleotide
      hybridization. Segregation analysis was then performed. RESULTS: We found a
      significant association (p = 0.009) between the glutamine 27 beta2-adrenoceptor
      polymorphism and elevated levels of IgE, which was supported by the observation
      of linkage between IgE and beta2-adrenoceptor polymorphisms at locus 27 (p =
      0.037). However, there was no association between either the arginine-glycine 16
      or the glutamine-glutamate 27 beta2-adrenoceptor polymorphism and an increased
      risk of asthma or atopy per se. CONCLUSION: The glutamine 27 beta2-adrenoceptor
      polymorphism appears to contribute to IgE variability in families with asthma.
      However, it seems that although both amino acid 16 and 27 beta2-adrenoceptor
      polymorphisms are disease-modifying in subjects with asthma, they do not
      contribute markedly to the development of the asthmatic phenotype.

PMID- 9275151
TI  - Induction of systemic immunologic tolerance to beta-lactoglobulin by oral
      administration of a whey protein hydrolysate.
AB  - BACKGROUND: Oral administration of an antigen has been shown to suppress the
      specific immune response to this antigen. This approach, called oral tolerance,
      has been demonstrated with intact proteins in animal models for prevention of
      allergy and autoimmune diseases. OBJECTIVE: The purpose of this study was to
      determine whether oral tolerance can be induced with protein peptides. Partially
      hydrolyzed and extensively hydrolyzed cow's milk formulas were compared for their
      capacity to induce tolerance to cow's milk proteins. METHODS: Five-week-old
      Sprague-Dawley rats were fed cow's milk formulas ad libitum from day 1 to day 19.
      All animals were immunized with beta-lactoglobulin and ovalbumin on day 5 and
      bled on day 19. Sera were analyzed for specific IgE and IgG antibodies by ELISA
      and for functional IgE response by in vitro mast cell mediator (tritiated
      serotonin) release. In vivo modulation of intestinal mast cells was analyzed by
      the specific release of the rat mast cell protease II, and T-cell response was
      determined by tritiated thymidine incorporation into lymph node lymphocytes.
      RESULTS: Oral administration of a partially hydrolyzed cow's milk formula
      suppresses specific serum IgE and IgG anti-beta-lactoglobulin antibodies, as well
      as mediator release from rat mast cells and T-lymphocyte response. This
      suppression was shown to be antigen-specific and dose-dependent. An extensively
      hydrolyzed formula was unable to achieve the induction of such an oral tolerance.
      CONCLUSION: These results support the view that partially hydrolyzed proteins are
      able to induce specific oral tolerance, whereas extensively hydrolyzed proteins
      are not.

PMID- 9275152
TI  - Conversion of the CD4+ T cell profile from T(H2)-dominant type to T(H1)-dominant
      type after varicella-zoster virus infection in atopic dermatitis.
AB  - Skin lesions of atopic dermatitis were examined for cytokine expression by
      reverse transcription-polymerase chain reaction. The profile of mRNA for various
      cytokines revealed that both T(H1) and T(H2) types of CD4+ T cells, probably
      including T(H0) type, infiltrate into the skin lesion. We observed that atopic
      skin lesions improved after varicella infection. In such lesions, expression of
      T(H1) type cytokines predominated. The peripheral blood T cells from atopic
      patients exhibited a differentiation into T(H2) type cells upon in vitro
      stimulation with mite antigen. In contrast they differentiated into T(H1) type
      cells upon stimulation by varicella antigen. Since IL-12 has been reported to
      switch the in vitro recall response of allergen-specific T cells of atopic donors
      from a T(H2)- to a T(H1)-like phenotype, we examined its local production in
      varicella lesions. IL-12 p35 and p40 mRNA were expressed in fresh lesions.
      Peripheral blood mononuclear cells from atopic patients expressed p40 mRNA upon
      in vitro stimulation with live varicella zoster virus, but they did not show p40
      mRNA without stimulation. This finding suggested that in atopic skin lesions
      containing the virus, IL-12 was produced and the cell type was changed to T(H1)
      type-predominance. These results suggested that patients with atopic dermatitis
      always have highly reactive CD4+ T cells infiltrating into their skin, and that
      the switch to T(H1) or T(H2) dominance is related to whether the lesion is
      improved or exacerbated.

PMID- 9275153
TI  - All change at Holliday junction.

PMID- 9275155
TI  - Linking topography of its potential surface with the dynamics of folding of a
      protein model.
AB  - The "3-color, 46-bead" model of a folding polypeptide is the vehicle for adapting
      to proteins a mode of analysis used heretofore for atomic clusters, to relate the
      topography of the potential surface to the dynamics that lead to formation of
      selected structures. The analysis is based on sequences of stationary points
      successive minima, joined by saddles-that rise monotonically in energy from basin
      bottoms. Like structure-seeking clusters, the potential surface of the model
      studied here is staircase-like, rather than sawtooth-like, with highly collective
      motions required for passage from one minimum to the next. The surface has
      several deep basins whose minima correspond to very similar structures, but which
      are separated by high energy barriers.

PMID- 9275158
TI  - Multiple pathways to bypass the enhancer requirement of sigma 54 RNA polymerase:
      roles for DNA and protein determinants.
AB  - Sigma 54 is a required factor for bacterial RNA polymerase to respond to
      enhancers and directs a mechanism that is a hybrid between bacterial and
      eukaryotic transcription. Three pathways were found that bypass the enhancer
      requirement in vitro. These rely on either deletion of the sigma 54 N terminus or
      destruction of the DNA consensus -12 promoter recognition element or altering
      solution conditions to favor transient DNA melting. Each of these allows unstable
      heparin-sensitive pre-initiation complexes to form that can be driven to
      transcribe in the absence of both enhancer protein and ATP beta-gamma hydrolysis.
      These disparate pathways are proposed to have a common basis in that multiple N
      terminal contacts may mediate the interactions between the polymerase and the DNA
      region where melting originates. The results raise possibilities for common
      features of open complex formation by different RNA polymerases.

PMID- 9275159
TI  - Heterogeneous nuclear ribonucleoprotein A1 binds to the transcription-regulatory
      region of mouse hepatitis virus RNA.
AB  - A cellular protein, previously described as p35/38, binds to the complementary (
      )-strand of the leader RNA and intergenic (IG) sequence of mouse hepatitis virus
      (MHV) RNA. The extent of the binding of this protein to IG sites correlates with
      the efficiency of the subgenomic mRNA transcription from that IG site, suggesting
      that it is a requisite transcription factor. We have purified this protein and
      determined by partial peptide sequencing that it is heterogeneous nuclear
      ribonucleoprotein (hnRNP) A1, an abundant, primarily nuclear protein. hnRNP A1
      shuttles between the nucleus and cytoplasm and plays a role in the regulation of
      alternative RNA splicing. The MHV(-)-strand leader and IG sequences conform to
      the consensus binding motifs of hnRNP A1. Recombinant hnRNP A1 bound to these two
      RNA regions in vitro in a sequence-specific manner. During MHV infection, hnRNP
      A1 relocalizes from the nucleus to the cytoplasm, where viral replication occurs.
      These data suggest that hnRNP A1 is a cellular factor that regulates the RNA
      dependent RNA transcription of the virus.

PMID- 9275160
TI  - Substrate-induced conformational change in a trimeric ornithine
      transcarbamoylase.
AB  - The crystal structure of Escherichia coli ornithine transcarbamoylase (OTCase, EC
      2.1.3.3) complexed with the bisubstrate analog N-(phosphonacetyl)-L-ornithine
      (PALO) has been determined at 2.8-A resolution. This research on the structure of
      a transcarbamoylase catalytic trimer with a substrate analog bound provides new
      insights into the linkages between substrate binding, protein-protein
      interactions, and conformational change. The structure was solved by molecular
      replacement with the Pseudomonas aeruginosa catabolic OTCase catalytic trimer
      (Villeret, V., Tricot, C., Stalon, V. & Dideberg, O. (1995) Proc. Natl. Acad.
      Sci. USA 92, 10762-10766; Protein Data Bank reference pdb 1otc) as the model and
      refined to a crystallographic R value of 21.3%. Each polypeptide chain folds into
      two domains, a carbamoyl phosphate binding domain and an L-ornithine binding
      domain. The bound inhibitor interacts with the side chains and/or backbone atoms
      of Lys-53, Ser-55, Thr-56, Arg-57, Thr-58, Arg-106, His-133, Asn-167, Asp-231,
      Met-236, Leu-274, Arg-319 as well as Gln-82 and Lys-86 from an adjacent chain.
      Comparison with the unligated P. aeruginosa catabolic OTCase structure indicates
      that binding of the substrate analog results in closure of the two domains of
      each chain. As in E. coli aspartate transcarbamoylase, the 240s loop undergoes
      the largest conformational change upon substrate binding. The clinical
      implications for human OTCase deficiency are discussed.

PMID- 9275161
TI  - Localization of the C terminus of the assembly domain of hepatitis B virus capsid
      protein: implications for morphogenesis and organization of encapsidated RNA.
AB  - The capsid protein of hepatitis B virus, consisting of an "assembly" domain
      (residues 1-149) and an RNA-binding "protamine" domain (residues 150-183),
      assembles from dimers into icosahedral capsids of two different sizes. The C
      terminus of the assembly domain (residues 140-149) functions as a morphogenetic
      switch, longer C termini favoring a higher proportion of the larger capsids, it
      also connects the protamine domain to the capsid shell. We now have defined the
      location of this peptide in capsids assembled in vitro by engineering a mutant
      assembly domain with a single cysteine at its C terminus (residue 150), labeling
      it with a gold cluster and visualizing the cluster by cryo-electron microscopy.
      The labeled protein is unimpaired in its ability to form capsids. Our density map
      reveals a single undecagold cluster under each fivefold and quasi-sixfold vertex,
      connected to sites at either end of the undersides of the dimers. Considering the
      geometry of the vertices, the C termini must be more crowded at the fivefolds.
      Thus, a bulky C terminus would be expected to favor formation of the larger (T =
      4) capsids, which have a greater proportion of quasi-sixfolds. Capsids assembled
      by expressing the full-length protein in Escherichia coli package bacterial RNAs
      in amounts equivalent to the viral pregenome. Our density map of these capsids
      reveals a distinct inner shell of density-the RNA. The RNA is connected to the
      protein shell via the C-terminal linkers and also makes contact around the dimer
      axes.

PMID- 9275163
TI  - DNA bending and the initiation of transcription at sigma54-dependent bacterial
      promoters.
AB  - We have examined the effects on transcription initiation of promoter and enhancer
      strength and of the curvature of the DNA separating these entities on wild-type
      and mutated enhancer-promoter regions at the Escherichia coli sigma54-dependent
      promoters glnAp2 and glnHp2 on supercoiled and linear DNA. Our results, together
      with previously reported observations by other investigators, show that the
      initiation of transcription on linear DNA requires a single intrinsic or induced
      bend in the DNA, as well as a promoter with high affinity for sigma54-RNA
      polymerase, but on supercoiled DNA requires either such a bend or a high affinity
      promoter but not both. The examination of the DNA sequence of all nif gene
      activator- or nitrogen regulator I-sigma54 promoters reveals that those lacking a
      binding site for the integration host factor have an intrinsic single bend in the
      DNA separating enhancer from promoter.

PMID- 9275162
TI  - Neuregulin-3 (NRG3): a novel neural tissue-enriched protein that binds and
      activates ErbB4.
AB  - We describe the identification of Neuregulin-3 (NRG3), a novel protein that is
      structurally related to the neuregulins (NRG1). The NRG1/neuregulins are a
      diverse family of proteins that arise by alternative splicing from a single gene.
      These proteins play an important role in controlling the growth and
      differentiation of glial, epithelial, and muscle cells. The biological effects of
      NRG1 are mediated by receptor tyrosine kinases ErbB2, ErbB3, and ErbB4. However,
      genetic studies have suggested that the activity of ErbB4 may also be regulated
      in the central nervous system by a ligand distinct from NRG1. NRG3 is predicted
      to contain an extracellular domain with an epidermal growth factor (EGF) motif, a
      transmembrane domain, and a large cytoplasmic domain. We show that the EGF-like
      domain of NRG3 binds to the extracellular domain of ErbB4 in vitro. Moreover,
      NRG3 binds to ErbB4 expressed on cells and stimulates tyrosine phosphorylation of
      this receptor. The expression of NRG3 is highly restricted to the developing and
      adult nervous system. These data suggest that NRG3 is a novel, neural-enriched
      ligand for ErbB4.

PMID- 9275164
TI  - Phylogeny of mRNA capping enzymes.
AB  - The m7GpppN cap structure of eukaryotic mRNA is formed cotranscriptionally by the
      sequential action of three enzymes: RNA triphosphatase, RNA guanylyltransferase,
      and RNA (guanine-7)-methyltransferase. A multifunctional polypeptide containing
      all three active sites is encoded by vaccinia virus. In contrast, fungi and
      Chlorella virus encode monofunctional guanylyltransferase polypeptides that lack
      triphosphatase and methyltransferase activities. Transguanylylation is a two
      stage reaction involving a covalent enzyme-GMP intermediate. The active site is
      composed of six protein motifs that are conserved in order and spacing among
      yeast and DNA virus capping enzymes. We performed a structure-function analysis
      of the six motifs by targeted mutagenesis of Ceg1, the Saccharomyces cerevisiae
      guanylyltransferase. Essential acidic, basic, and aromatic functional groups were
      identified. The structural basis for covalent catalysis was illuminated by
      comparing the mutational results with the crystal structure of the Chlorella
      virus capping enzyme. The results also allowed us to identify the capping enzyme
      of Caenorhabditis elegans. The 573-amino acid nematode protein consists of a C
      terminal guanylyltransferase domain, which is homologous to Ceg1 and is strictly
      conserved with respect to all 16 amino acids that are essential for Ceg1
      function, and an N-terminal phosphatase domain that bears no resemblance to the
      vaccinia triphosphatase domain but, instead, has strong similarity to the
      superfamily of protein phosphatases that act via a covalent phosphocysteine
      intermediate.

PMID- 9275165
TI  - An intercalation inhibitor altering the target selectivity of DNA damaging
      agents: synthesis of site-specific aflatoxin B1 adducts in a p53 mutational
      hotspot.
AB  - Aflatoxin B1 (AFB1) is a potent human carcinogen implicated in the etiology of
      hepatocellular carcinoma. Upon metabolic activation to the reactive epoxide, AFB1
      forms DNA adducts primarily at the N7 position of guanines. To elucidate more
      fully the molecular mechanism of AFB1-induced mutagenesis, an intercalation
      inhibitor was designed to probe the effects of intercalation by AFB1 epoxide on
      its reaction with DNA. DNA duplexes were prepared consisting of a target strand
      containing multiple potentially reactive guanines and a nontarget strand
      containing a cis-syn thymidine-benzofuran photoproduct. Because the covalently
      linked benzofuran moiety physically occupies an intercalation site, we reasoned
      that such a site would be rendered inaccessible to AFB1 epoxide. By strategic
      positioning of this intercalation inhibitor in the intercalation site 5' to a
      specific guanine, the adduct yield at that site was greatly diminished,
      indicating that intercalation by AFB1 epoxide contributes favorably to adduct
      formation. Using this approach it has been possible to simplify the production of
      site-specifically modified oligonucleotides containing AFB1 adducts in the
      sequence context of a p53 mutational hotspot. Moreover, we report herein
      isolation of site-specifically AFB1-modified oligonucleotides in sequences
      containing multiple guanines. Use of intercalation inhibitors will facilitate
      both investigation of the ability of other carcinogens to intercalate into DNA
      and the synthesis of specific carcinogen-DNA adducts.

PMID- 9275166
TI  - The yeast peptide-methionine sulfoxide reductase functions as an antioxidant in
      vivo.
AB  - A gene homologous to methionine sulfoxide reductase (msrA) was identified as the
      predicted ORF (cosmid 9379) in chromosome V of Saccharomyces cerevisiae encoding
      a protein of 184 amino acids. The corresponding protein has been expressed in
      Escherichia coli and purified to homogeneity. The recombinant yeast MsrA
      possessed the same substrate specificity as the other known MsrA enzymes from
      mammalian and bacterial cells. Interruption of the yeast gene resulted in a null
      mutant, DeltamsrA::URA3 strain, which totally lost its cellular MsrA activity and
      was shown to be more sensitive to oxidative stress in comparison to its wild-type
      parent strain. Furthermore, high levels of free and protein-bound methionine
      sulfoxide were detected in extracts of msrA mutant cells relative to their wild
      type parent cells, under various oxidative stresses. These findings show that
      MsrA is responsible for the reduction of methionine sulfoxide in vivo as well as
      in vitro in eukaryotic cells. Also, the results support the proposition that MsrA
      possess an antioxidant function. The ability of MsrA to repair oxidative damage
      in vivo may be of singular importance if methionine residues serve as
      antioxidants.

PMID- 9275167
TI  - On the reaction mechanism of L-lactate oxidase: quantitative structure-activity
      analysis of the reaction with para-substituted L-mandelates.
AB  - The rate constants for reduction of the flavoenzyme, L-lactate oxidase, and a
      mutant (in which alanine 95 is replaced by glycine), by a series of para
      substituted mandelates, in both the 2-1H- and 2-2H- forms, have been measured by
      rapid reaction spectrophotometry. In all cases, significant isotope effects
      (1H/2H = 3-7) on the rate constants of flavin reduction were found, indicating
      that flavin reduction is a direct measure of alpha-C-H bond breakage. The rate
      constants show only a small influence of the electronic characteristics of the
      substituents, but show a good correlation when combined with some substituent
      volume parameters. A surprisingly good correlation is found with the molecular
      mass of the substrate. The results are compatible with any mechanism in which
      there is little development of charge in the transition state. This could be a
      transfer of hydride to the flavin N(5) position or a synchronous mechanism in
      which the alpha-C-H is formally abstracted as a H+ while the resulting charge is
      simultaneously neutralized by another event.

PMID- 9275168
TI  - Fe-catalyzed cleavage of the alpha subunit of Na/K-ATPase: evidence for
      conformation-sensitive interactions between cytoplasmic domains.
AB  - Incubation of Na/K-ATPase with ascorbate plus H2O2 produces specific cleavage of
      the alpha subunit. Five fragments with intact C termini and complementary
      fragments with intact N termini were observed. The beta subunit is not cleaved.
      Cleavages depend on the presence of contaminant or added Fe2+ ions, as inferred
      by suppression of cleavages with nonspecific metal complexants (histidine, EDTA,
      phenanthroline) or the Fe3+-specific complexant desferrioxamine, or acceleration
      of cleavages by addition of low concentrations of Fe2+ but not of other heavy
      metal ions. Na/K-ATPase is inactivated in addition to cleavage, and both effects
      are insensitive to OH. radical scavengers. Cleavages are sensitive to
      conformation. In low ionic strength media (E2) or media containing Rb ions
      [E2(Rb)], cleavage is much faster than in high ionic strength media (E1) or media
      containing Na ions (E1Na). N-terminal fragments and two C-terminal fragments (N
      terminals E214 and V712) have been identified by amino acid sequencing.
      Approximate positions of other cleavages were determined with specific
      antibodies. The results suggest that Fe2+ (or Fe3+) ions bind with high affinity
      at the cytoplasmic surface and catalyze cleavages of peptide bonds close to the
      Fe2+ (or Fe3+) ion. Thus, cleavage patterns can provide information on spatial
      organization of the polypeptide chain. We propose that highly conserved regions
      of the alpha subunit, within the minor and major cytoplasmic loops, interact in
      the E2 or E2(Rb) conformations but move apart in the E1 or E1Na conformations. We
      discuss implications of domain interactions for the energy transduction
      mechanism. Fe-catalyzed cleavages may be applicable to other P-type pumps or
      membrane proteins.

PMID- 9275169
TI  - Identification of an intramolecular interaction between small regions in type V
      adenylyl cyclase that influences stimulation of enzyme activity by Gsalpha.
AB  - Using the full-length and two engineered soluble forms (C1-C2 and Cla-C2) of type
      V adenylyl cyclase (ACV), we have investigated the role of an intramolecular
      interaction in ACV that modulates the ability of the alpha subunit of the
      stimulatory GTP-binding protein of AC (Gsalpha) to stimulate enzyme activity.
      Concentration-response curves with Gsalpha suggested the presence of high and low
      affinity sites on ACV, which interact with the G protein. Activation of enzyme by
      Gsalpha interaction at these two sites was most apparent in the C1a-C2 form of
      ACV, which lacks the C1b region (K572-F683). Yeast two-hybrid data demonstrated
      that the C1b region interacted with the C2 region and its 64-aa subdomain, C2I.
      Using peptides corresponding to the C2I region of ACV, we investigated the role
      of the C1b/C2I interaction on Gsalpha-mediated stimulation of C1-C2 and full
      length ACV. Our data demonstrate that a 10-aa peptide corresponding to L1042
      T1051 alters the profile of the activation curves of full-length and C1-C2 forms
      of ACV by different Gsalpha concentrations to mimic the activation profile
      observed with C1a-C2 ACV. The various peptides used in our studies did not alter
      forskolin-mediated stimulation of full-length and C1-C2 forms of ACV. We conclude
      that the C1b region of ACV interacts with the 10-aa region (L1042-T1051) in the
      C2 domain of the enzyme to modulate Gsalpha-elicited stimulation of activity.

PMID- 9275170
TI  - Pyruvate ferredoxin oxidoreductase from the hyperthermophilic archaeon,
      Pyrococcus furiosus, functions as a CoA-dependent pyruvate decarboxylase.
AB  - Pyruvate ferredoxin oxidoreductase (POR) has been previously purified from the
      hyperthermophilic archaeon, Pyrococcus furiosus, an organism that grows optimally
      at 100 degrees C by fermenting carbohydrates and peptides. The enzyme contains
      thiamine pyrophosphate and catalyzes the oxidative decarboxylation of pyruvate to
      acetyl-CoA and CO2 and reduces P. furiosus ferredoxin. Here we show that this
      enzyme also catalyzes the formation of acetaldehyde from pyruvate in a CoA
      dependent reaction. Desulfocoenzyme A substituted for CoA showing that the
      cofactor plays a structural rather than a catalytic role. Ferredoxin was not
      necessary for the pyruvate decarboxylase activity of POR, nor did it inhibit
      acetaldehyde production. The apparent Km values for CoA and pyruvate were 0.11 mM
      and 1.1 mM, respectively, and the optimal temperature for acetaldehyde formation
      was above 90 degrees C. These data are comparable to those previously determined
      for the pyruvate oxidation reaction of POR. At 80 degrees C (pH 8.0), the
      apparent Vm value for pyruvate decarboxylation was about 40% of the apparent Vm
      value for pyruvate oxidation rate (using P. furiosus ferredoxin as the electron
      acceptor). Tentative catalytic mechanisms for these two reactions are presented.
      In addition to POR, three other 2-keto acid ferredoxin oxidoreductases are
      involved in peptide fermentation by hyperthermophilic archaea. It is proposed
      that the various aldehydes produced by these oxidoreductases in vivo are used by
      two aldehyde-utilizing enzymes, alcohol dehydrogenase and aldehyde ferredoxin
      oxidoreductase, the physiological roles of which were previously unknown.

PMID- 9275171
TI  - Dominant transformation by mutated human ras genes in vitro requires more than
      100 times higher expression than is observed in cancers.
AB  - The gene-mutation-cancer hypothesis holds that mutated cellular protooncogenes,
      such as point-mutated proto-ras, "play a dominant part in cancer," because they
      are sufficient to transform transfected mouse cell lines in vitro [Alberts, B.,
      Bray, D., Lewis, J., Raff, M., Roberts, K. & Watson, J. D. (1994) Molecular
      Biology of the Cell (Garland, New York)]. However, in cells transformed in vitro
      mutated human ras genes are expressed more than 100-fold than in the cancers from
      which they are isolated. In view of the discrepancy between the very low levels
      of ras transcription in cancers and the very high levels in cells transformed in
      vitro, we have investigated the minimal level of human ras expression for
      transformation in vitro. Using point-mutated human ras genes recombined with
      different promoters from either human metallothionein-IIA or human fibronectin or
      from retroviruses we found dominant in vitro transformation of the mouse C3H cell
      line only with ras genes linked to viral promoters. These ras genes were
      expressed more than 120-fold higher than are native ras genes of C3H cells. The
      copy number of transfected ras genes ranged from 2-6 in our system. In addition,
      nondominant transformation was observed in a small percentage (2-7%) of C3H cells
      transfected with ras genes that are expressed less than 20 times higher than
      native C3H ras genes. Because over 90% of cells expressing ras at this moderately
      enhanced level were untransformed, transformation must follow either a
      nondominant ras mechanism or a non-ras mechanism. We conclude that the mutated,
      but normally expressed, ras genes found in human and animal cancers are not
      likely to "play a dominant part in cancer." The conclusion that mutated ras genes
      are not sufficient or dominant for cancer is directly supported by recent
      discoveries of mutated ras in normal animals, and in benign human tissue, "which
      has little potential to progress" [Jen, J., Powell, S. M., Papadopoulos, N.,
      Smith, K. J., Hamilton, S. R., Vogelstein, B. & Kinzler, K. W. (1994) Cancer Res.
      54, 5523-5526]. Even the view that mutated ras is necessary for cancer is hard to
      reconcile with (i) otherwise indistinguishable cancers with and without ras
      mutations, (ii) metastases of the same human cancers with and without ras
      mutations, (iii) retroviral ras genes that are oncogenic without point mutations,
      and (iv) human tumor cells having spontaneously lost ras mutation but not
      tumorigencity.

PMID- 9275172
TI  - Crystal structures of the copper and nickel complexes of RNase A: metal-induced
      interprotein interactions and identification of a novel copper binding motif.
AB  - We report the crystal structures of the copper and nickel complexes of RNase A.
      The overall topology of these two complexes is similar to that of other RNase A
      structures. However, there are significant differences in the mode of binding of
      copper and nickel. There are two copper ions per molecule of the protein, but
      there is only one nickel ion per molecule of the protein. Significant changes
      occur in the interprotein interactions as a result of differences in the
      coordinating groups at the common binding site around His-105. Consequently, the
      copper- and nickel-ion-bound dimers of RNase A act as nucleation sites for
      generating different crystal lattices for the two complexes. A second copper ion
      is present at an active site residue His-119 for which all the ligands are from
      one molecule of the protein. At this second site, His-119 adopts an inactive
      conformation (B) induced by the copper. We have identified a novel copper binding
      motif involving the alpha-amino group and the N-terminal residues.

PMID- 9275173
TI  - A molecular level picture of the stabilization of A-DNA in mixed ethanol-water
      solutions.
AB  - Advances in computer power, methodology, and empirical force fields now allow
      routine "stable" nanosecond-length molecular dynamics simulations of DNA in
      water. The accurate representation of environmental influences on structure
      remains a major, unresolved issue. In contrast to simulations of A-DNA in water
      (where an A-DNA to B-DNA transition is observed) and in pure ethanol (where
      disruption of the structure is observed), A-DNA in approximately 85% ethanol
      solution remains in a canonical A-DNA geometry as expected. The stabilization of
      A-DNA by ethanol is likely due to disruption of the spine of hydration in the
      minor groove and the presence of ion-mediated interhelical bonds and extensive
      hydration across the major groove.

PMID- 9275175
TI  - The 2.0-A resolution crystal structure of a trimeric antibody fragment with
      noncognate VH-VL domain pairs shows a rearrangement of VH CDR3.
AB  - The 2.0-A resolution x-ray crystal structure of a novel trimeric antibody
      fragment, a "triabody," has been determined. The trimer is made up of
      polypeptides constructed in a manner identical to that previously described for
      some "diabodies": a VL domain directly fused to the C terminus of a VH domain
      i.e., without any linker sequence. The trimer has three Fv heads with the
      polypeptides arranged in a cyclic, head-to-tail fashion. For the particular
      structure reported here, the polypeptide was constructed with a VH domain from
      one antibody fused to the VL domain from an unrelated antibody giving rise to
      "combinatorial" Fvs upon formation of the trimer. The structure shows that the
      exchange of the VL domain from antibody B1-8, a Vlambda domain, with the VL
      domain from antibody NQ11, a Vkappa domain, leads to a dramatic conformational
      change in the VH CDR3 loop of antibody B1-8. The magnitude of this change is
      similar to the largest of the conformational changes observed in antibody
      fragments in response to antigen binding. Combinatorial pairing of VH and VL
      domains constitutes a major component of antibody diversity. Conformationally
      flexible antigen-binding sites capable of adapting to the specific CDR3 loop
      context created upon VH-VL pairing may be employed by the immune system to
      maximize the structural diversity of the immune response.

PMID- 9275174
TI  - Probes bound to myosin Cys-707 rotate during length transients in contraction.
AB  - It is widely conjectured that muscle shortens because portions of myosin
      molecules (the "cross-bridges") impel the actin filament to which they
      transiently attach and that the impulses result from rotation of the cross
      bridges. Crystallography indicates that a cross-bridge is articulated-consisting
      of a globular catalytic/actin-binding domain and a long lever arm that may
      rotate. Conveniently, a rhodamine probe with detectable attitude can be attached
      between the globular domain and the lever arm, enabling the observer to tell
      whether the anchoring region rotates. Well-established signature effects observed
      in shortening are tension changes resulting from the sudden release or quick
      stretch of active muscle fibers. In this investigation we found that closely
      correlated with such tension changes are changes in the attitude of the rhodamine
      probes. This correlation strongly supports the conjecture about how shortening is
      achieved.

PMID- 9275176
TI  - Independent mobility of catalytic and regulatory domains of myosin heads.
AB  - The recent determination of the myosin head atomic structure has led to a new
      model of muscle contraction, according to which mechanical torque is generated in
      the catalytic domain and amplified by the lever arm made of the regulatory domain
      [Fisher, A. J., Smith, C. A., Thoden, J., Smith, R., Sutoh, K., Holden, H. M. &
      Rayment, I. (1995) Biochemistry 34, 8960-8972]. A crucial aspect of this model is
      the ability of the regulatory domain to move independently of the catalytic
      domain. Saturation transfer-EPR measurements of mobility of these two domains in
      myosin filaments give strong support for this notion. The catalytic domain of the
      myosin head was labeled at Cys-707 with indane dione spin label; the regulatory
      domain was labeled at the single cysteine residue of the essential light chain
      and exchanged into myosin. The mobility of the regulatory domain in myosin
      filaments was characterized by an effective rotational correlation time (tauR)
      between 24 and 48 micros. In contrast, the mobility of the catalytic domain was
      found to be tauR = 5-9 micros. This difference in mobility between the two
      domains existed only in the filament form of myosin. In the monomeric form, or
      when bound to actin, the mobility of the two domains in myosin was
      indistinguishable, with tauR = 1-4 micros and >1,000 micros, respectively.
      Therefore, the observed difference in filaments cannot be ascribed to differences
      in local conformations of the spin-labeled sites. The most straightforward
      interpretation suggests a flexible hinge between the two domains, which would
      have to stiffen before force could be generated.

PMID- 9275177
TI  - Wild-type p53 triggers a rapid senescence program in human tumor cells lacking
      functional p53.
AB  - The p53 tumor suppressor gene has been shown to play an important role in
      determining cell fate. Overexpression of wild-type p53 in tumor cells has been
      shown to lead to growth arrest or apoptosis. Previous studies in fibroblasts have
      provided indirect evidence for a link between p53 and senescence. Here we show,
      using an inducible p53 expression system, that wild-type p53 overexpression in EJ
      bladder carcinoma cells, which have lost functional p53, triggers the rapid onset
      of G1 and G2/M growth arrest associated with p21 up-regulation and repression of
      mitotic cyclins (cyclin A and B) and cdc2. Growth arrest in response to p53
      induction became irreversible within 48-72 h, with cells exhibiting morphological
      features as well as specific biochemical and ultrastructural markers of the
      senescent phenotype. These findings provide direct evidence that p53
      overexpression can activate the rapid onset of senescence in tumor cells.

PMID- 9275178
TI  - Identification and classification of 16 new kinesin superfamily (KIF) proteins in
      mouse genome.
AB  - KIF (kinesin superfamily) proteins are microtubule-dependent molecular motors
      that play important roles in intracellular transport and cell division. The
      extent to which KIFs are involved in various transporting phenomena, as well as
      their regulation mechanism, are unknown. The identification of 16 new KIFs in
      this report doubles the existing number of KIFs known in the mouse. Conserved
      nucleotide sequences in the motor domain were amplified by PCR using cDNAs of
      mouse nervous tissue, kidney, and small intestine as templates. The new KIFs were
      studied with respect to their expression patterns in different tissues,
      chromosomal location, and molecular evolution. Our results suggest that (i) there
      is no apparent tendency among related subclasses of KIFs of cosegregation in
      chromosomal mapping, and (ii) according to their tissue distribution patterns,
      KIFs can be divided into two classes-i.e., ubiquitous and specific tissue
      dominant. Further characterization of KIFs may elucidate unknown fundamental
      phenomena underlying intracellular transport. Finally, we propose a
      straightforward nomenclature system for the members of the mouse kinesin
      superfamily.

PMID- 9275179
TI  - Phosphorylation of insulin receptor substrate 1 by glycogen synthase kinase 3
      impairs insulin action.
AB  - The phosphorylation of insulin receptor substrate 1 (IRS-1) on tyrosine residues
      by the insulin receptor (IR) tyrosine kinase is involved in most of the
      biological responses of insulin. IRS-1 mediates insulin signaling by recruiting
      SH2 proteins through its multiple tyrosine phosphorylation sites. The
      phosphorylation of IRS-1 on serine/threonine residues also occurs in cells;
      however, the particular protein kinase(s) promoting this type of phosphorylation
      are unknown. Here we report that glycogen synthase kinase 3 (GSK-3) is capable of
      phosphorylating IRS-1 and that this modification converts IRS-1 into an inhibitor
      of IR tyrosine kinase activity in vitro. Expression of wild-type GSK-3 or an
      "unregulated" mutant of the kinase (S9A) in CHO cells overexpressing IRS-1 and
      IR, resulted in increased serine phosphorylation levels of IRS-1, suggesting that
      IRS-1 is a cellular target of GSK-3. Furthermore, insulin-induced tyrosine
      phosphorylation of IRS-1 and IR was markedly suppressed in cells expressing wild
      type or the S9A mutant, indicating that expression of GSK-3 impairs IR tyrosine
      kinase activity. Taken together, our studies suggest a new role for GSK-3 in
      attenuating insulin signaling via its phosphorylation of IRS-1 and may provide
      new insight into mechanisms important in insulin resistance.

PMID- 9275180
TI  - Histone underacetylation is an ancient component of mammalian X chromosome
      inactivation.
AB  - Underacetylation of histone H4 is thought to be involved in the molecular
      mechanism of mammalian X chromosome inactivation, which is an important model
      system for large-scale genetic control in eukaryotes. However, it has not been
      established whether histone underacetylation plays a critical role in the
      multistep inactivation pathway. Here we demonstrate differential histone H4
      acetylation between the X chromosomes of a female marsupial, Macropus eugenii.
      Histone underacetylation is the only molecular aspect of X inactivation known to
      be shared by marsupial and eutherian mammals. Its strong evolutionary
      conservation implies that, unlike DNA methylation, histone underacetylation was a
      feature of dosage compensation in a common mammalian ancestor, and is therefore
      likely to play a central role in X chromosome inactivation in all mammals.

PMID- 9275181
TI  - Late memory-related genes in the hippocampus revealed by RNA fingerprinting.
AB  - Although long-term memory is thought to require a cellular program of gene
      expression and increased protein synthesis, the identity of proteins critical for
      associative memory is largely unknown. We used RNA fingerprinting to identify
      candidate memory-related genes (MRGs), which were up-regulated in the hippocampus
      of water maze-trained rats, a brain area that is critically involved in spatial
      learning. Two of the original 10 candidate genes implicated by RNA
      fingerprinting, the rat homolog of the ryanodine receptor type-2 and glutamate
      dehydrogenase (EC 1.4.1.3), were further investigated by Northern blot analysis,
      reverse transcription-PCR, and in situ hybridization and confirmed as MRGs with
      distinct temporal and regional expression. Successive RNA screening as
      illustrated here may help to reveal a spectrum of MRGs as they appear in distinct
      domains of memory storage.

PMID- 9275182
TI  - Centrosome positioning and directionality of cell movements.
AB  - In several cell types, an intriguing correlation exists between the position of
      the centrosome and the direction of cell movement: the centrosome is located
      behind the leading edge, suggesting that it serves as a steering device for
      directional movement. A logical extension of this suggestion is that a change in
      the direction of cell movement is preceded by a reorientation, or shift, of the
      centrosome in the intended direction of movement. We have used a fusion protein
      of green fluorescent protein (GFP) and gamma-tubulin to label the centrosome in
      migrating amoebae of Dictyostelium discoideum, allowing us to determine the
      relationship of centrosome positioning and the direction of cell movement with
      high spatial and temporal resolution in living cells. We find that the extension
      of a new pseudopod in a migrating cell precedes centrosome repositioning. An
      average of 12 sec elapses between the initiation of pseudopod extension and
      reorientation of the centrosome. If no reorientation occurs within approximately
      30 sec, the pseudopod is retracted. Thus the centrosome does not direct a cell's
      migration. However, its repositioning stabilizes a chosen direction of movement,
      most probably by means of the microtubule system.

PMID- 9275183
TI  - p53-independent apoptosis induced by paclitaxel through an indirect mechanism.
AB  - The efficacy of chemotherapeutic agents may be determined by a number of
      different factors, including the genotype of the tumor cell. The p53 tumor
      suppressor gene frequently is mutated in human tumors, and this may contribute to
      chemotherapeutic resistance. We tested the requirement for wild-type p53 in the
      response of tumor cells to treatment with paclitaxel (trade name Taxol), an
      antineoplastic agent that stabilizes cellular microtubules. Although paclitaxel
      is broadly effective against human tumor xenografts in mice, including some known
      to carry p53 mutations, we found that p53-containing mouse tumor cells were
      significantly more sensitive to direct treatment with this drug than were p53
      deficient tumor cells. In an attempt to reconcile this apparent discrepancy, we
      examined the requirement for p53 in the cytotoxic effects of tumor necrosis
      factor alpha (TNF-alpha), a cytokine released from murine macrophages upon
      paclitaxel treatment. Conditioned medium from paclitaxel-treated macrophages was
      capable of inducing p53-independent apoptosis when applied to transformed mouse
      embryonic fibroblasts and was inhibitable by antibodies against TNF-alpha.
      Furthermore, in response to direct treatment with TNF-alpha, both wild-type and
      p53-deficient tumor cells underwent apoptosis to similar extents and with similar
      kinetics. Our results suggest that the efficacy of paclitaxel in vivo may be due
      not only to its microtubule-stabilizing activity, but its ability to activate
      local release of an apoptosis-inducing cytokine.

PMID- 9275184
TI  - Dictyostelium myosin II null mutant can still cap Con A receptors.
AB  - Cross-linked antigens on the surface of a motile cell cap at the trailing end of
      the cell. In Dictyostelium discoideum, myosin II null mutants have previously
      been reported to be unable to cap Con A receptors, although they are able to
      locomote. This finding implicated myosin II as an essential component of the
      capping mechanism, although not of the machinery for locomotion. Here we show
      that myosin II null mutants do cap Con A receptors, albeit less efficiently than
      does wild type. This shows that cap formation is not absolutely dependent on
      myosin II and that a close mechanistic relationship between capping, particle
      movement, and cell migration may still exist.

PMID- 9275186
TI  - Rer1p as common machinery for the endoplasmic reticulum localization of membrane
      proteins.
AB  - Rer1p, a Golgi membrane protein, is required for the correct localization of an
      endoplasmic reticulum (ER) membrane protein, Sec12p, by a retrieval mechanism
      from the cis-Golgi to the ER. To test whether or not the role of Rer1p is common
      to multiple ER membrane proteins, we examined the localization of two other ER
      membrane proteins, Sec71p and Sec63p, in the wild-type and rer1 mutant yeast
      cells, using their fusions with an alpha-mating factor precursor (Mfalpha1p).
      Although Sec71p and Sec63p have completely different topology from Sec12p, their
      Mfalpha1p fusion proteins were also mislocalized to the trans-Golgi in the rer1
      mutant. Overexpression of these fusions caused their mislocalization to the trans
      Golgi even in the wild-type cells, and this mislocalization was partially
      suppressed by the co-overexpression of Rer1p. Either Sec71p or an artificial
      chimeric protein whose ER localization depends on Rer1p gave a competitive effect
      on the localization of the Mfalpha1-Sec71p fusion, which was abolished in rer1.
      Thus, Rer1p appears to be one of the common limiting components in the retrieval
      machinery for ER membrane proteins. The results also suggest that Sec71p and
      Sec63p depend on ER-Golgi recycling, at least partly, for ER localization. We
      also examined the effect of a mutation in alpha-COP, a subunit of yeast coatomer,
      on the localization of these ER membrane proteins. The Mfalpha1p fusions of
      Sec12p, Sec71p, and Sec63p were all more or less mislocalized in ret1-1. These
      observations imply that the roles of Rer1p and coatomer are much more general
      than thought before.

PMID- 9275185
TI  - Activation of the c-Jun N-terminal kinase pathway by a novel protein kinase
      related to human germinal center kinase.
AB  - The c-Jun N-terminal kinase (JNK), or stress-activated protein kinase plays a
      crucial role in cellular responses stimulated by environmental stress and
      proinflammatory cytokines. However, the mechanisms that lead to the activation of
      the JNK pathway have not been elucidated. We have isolated a cDNA encoding a
      novel protein kinase that has significant sequence similarities to human germinal
      center kinase (GCK) and human hematopoietic progenitor kinase 1. The novel GCK
      like kinase (GLK) has a nucleotide sequence that encodes an ORF of 885 amino
      acids with 11 kinase subdomains. Endogenous GLK could be activated by UV
      radiation and proinflammatory cytokine tumor necrosis factor alpha. When
      transiently expressed in 293 cells, GLK specifically activated the JNK, but not
      the p42/44(MAPK)/extracellular signal-regulated kinase or p38 kinase signaling
      pathways. Interestingly, deletion of amino acids 353-835 in the putative C
      terminal regulatory region, or mutation of Lys-35 in the putative ATP-binding
      domain, markedly reduced the ability of GLK to activate JNK. This result
      indicates that both kinase activity and the C-terminal region of GLK are required
      for maximal activation of JNK. Furthermore, GLK-induced JNK activation could be
      inhibited by a dominant-negative mutant of mitogen-activated protein kinase
      kinase kinase 1 (MEKK1) or mitogen-activated protein kinase kinase 4/SAPK/ERK
      kinase 1 (SEK1), suggesting that GLK may function upstream of MEKK1 in the JNK
      signaling pathway.

PMID- 9275187
TI  - RanGTP-mediated nuclear export of karyopherin alpha involves its interaction with
      the nucleoporin Nup153.
AB  - Using binding assays, we discovered an interaction between karyopherin alpha2 and
      the nucleoporin Nup153 and mapped their interacting domains. We also isolated a
      15-kDa tryptic fragment of karyopherin beta1, termed beta1*, that contains a
      determinant for binding to the peptide repeat containing nucleoporin Nup98. In an
      in vitro assay in which export of endogenous nuclear karyopherin alpha from
      nuclei of digitonin-permeabilized cells was quantitatively monitored by indirect
      immunofluorescence with anti-karyopherin alpha antibodies, we found that
      karyopherin alpha export was stimulated by added GTPase Ran, required GTP
      hydrolysis, and was inhibited by wheat germ agglutinin. RanGTP-mediated export of
      karyopherin alpha was inhibited by peptides representing the interacting domains
      of Nup153 and karyopherin alpha2, indicating that the binding reactions detected
      in vitro are physiologically relevant and verifying our mapping data. Moreover,
      beta1*, although it inhibited import, did not inhibit export of karyopherin
      alpha. Hence, karyopherin alpha import into and export from nuclei are asymmetric
      processes.

PMID- 9275188
TI  - Compromised mitochondrial function leads to increased cytosolic calcium and to
      activation of MAP kinases.
AB  - We have investigated in rat pheochromacytoma PC12 cells the activation of the
      mitogen-activated protein kinases ERK1 and ERK2 by the mitochondrial uncoupler
      carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP). This treatment
      slowly decreases ATP levels to 30% of control, whereas the internal calcium level
      rises very rapidly to 250% of control, derived from internal stores. Tyrosine
      phosphorylation of ERK1 and ERK2 increases gradually, starting after 5 min of
      treatment, to reach a maximum at 30 min; the kinase activity reaches 250% when
      measured after 1 hr of treatment. The drop in ATP levels is slower still.
      Comparison of the time courses of the rapid rise in cytosolic calcium with the
      slower increase in ERK1 and ERK2 activation suggests one or more intermediate
      stages in this pathway. Chelation of cytosolic calcium with dimethyl bis-(o
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid abolished the FCCP-stimulated rise
      in internal calcium, as well as the tyrosine phosphorylation and the activation
      of the ERKs. Surprisingly, caffeine, which releases calcium from different
      internal stores, did not increase the tyrosine phosphorylation and did not
      activate the ERKs. The FCCP effect on calcium storage may be related to
      mitochondrial dysfunction in Alzheimer disease, which might result in ineffective
      buffering of cytosolic calcium that leads to mitogen-activated protein kinase
      activation and subsequent protein phosphorylations.

PMID- 9275189
TI  - The newt ribozyme is part of a riboprotein complex.
AB  - Strand-specific transcripts of a satellite DNA of the newts, Notophthalmus and
      Triturus, are present in cells in monomeric and multimeric sizes. These
      transcripts undergo self-catalyzed, site-specific cleavage in vitro: the reaction
      requires Mg2+ and is mediated by a "hammerhead" domain. Transcription of the newt
      ribozyme appears to be performed by RNA polymerase II under the control of a
      proximal sequence element and a distal sequence element. In vitro, the newt
      ribozyme can cleave in trans an RNA substrate, suggesting that in vivo it might
      be involved in RNA processing events, perhaps as a riboprotein complex. Here we
      show that the newt ribozyme is in fact present as a riboprotein particle of about
      12 S in the oocytes of Triturus. In addition, reconstitution experiments and gel
      shift analyses show that a complex is assembled in vitro on the monomeric
      ribozyme molecules. UV cross-linking studies identify a few polypeptide species,
      ranging from 31 to 65 kDa, associated to the newt ribozyme with different
      affinities. Finally, we find that an appropriate oligoribonucleotide substrate is
      specifically cleaved by the riboproteic activity in S-100 ovary extracts.

PMID- 9275191
TI  - Firefly "femmes fatales" acquire defensive steroids (lucibufagins) from their
      firefly prey.
AB  - Female fireflies of the genus Photuris, the so-called firefly "femmes fatales,"
      prey on male fireflies of the genus Photinus. The females are able to entrap the
      males by faking the flash signal characteristics of the Photinus female. We found
      that by feeding on Photinus males, Photuris females gain more than nutrients.
      They also acquire defensive steroidal pyrones called lucibufagins, which are
      contained in Photinus but which Photuris fireflies are unable to produce on their
      own. Photuris females that eat Photinus males or lucibufagin are rejected by
      Phidippus jumping spiders. Lucibufagin itself proved to be a deterrent to such
      spiders. Field-collected Photuris females contain lucibufagin in varying amounts.
      The more lucibufagin they contain the more unacceptable they are to Phidippus.

PMID- 9275190
TI  - Transcriptional regulation of the Xlim-1 gene by activin is mediated by an
      element in intron I.
AB  - The Xlim-1 gene is activated in the late blastula stage of Xenopus embryogenesis
      in the mesoderm, and its RNA product becomes concentrated in the Spemann
      organizer at early gastrula stage. A major regulator of early expression of Xlim
      1 is activin or an activin-like signal. We report experiments aiming to identify
      the activin response element in the Xlim-1 gene. The 5' flanking region of the
      gene contains a constitutive promoter that is not activin responsive, whereas
      sequences in the first intron mediate repression of basal promoter activity and
      stimulation by activin. An intron-derived fragment of 212 nt is the smallest
      element that could mediate activin responsiveness. Nodal and act-Vg1, factors
      with signaling properties similar to activin, also stimulated Xlim-1 reporter
      constructs, whereas BMP-4 did not stimulate or repress the constructs. The
      mechanism of activin regulation of Xlim-1 and the sequence of the response
      element are distinct from activin response elements of other genes studied so
      far.

PMID- 9275194
TI  - Character displacement in some Cnemidophorus lizards revisited: a phylogenetic
      analysis.
AB  - Ecological studies have demonstrated the role of competition in structuring
      communities; however, the importance of competition as a vehicle for evolution by
      natural selection and speciation remains unresolved. Study systems of insular
      faunas have provided several well known cases where ecological character
      displacement, coevolution of competitors leading to increased morphological
      separation, is thought to have occurred (e.g., anoline lizards and geospizine
      finches). Whiptail lizards (genus Cnemidophorus) from the islands of the Sea of
      Cortez and the surrounding mainland demonstrate a biogeographic pattern of
      morphological variation suggestive of character displacement. Two species of
      Cnemidophorus occur on the Baja peninsula, one relatively large (Cnemidophorus
      tigris) and one smaller (Cnemidophorus hyperythrus). Oceanic islands in the Sea
      of Cortez contain only single species, five of six having sizes intermediate to
      both species found on the Baja peninsula. On mainland Mexico C. hyperythrus is
      absent, whereas C. tigris is the smaller species in whiptail guilds. Here we
      construct a phylogeny using nucleotide sequences of the cytochrome b gene to
      infer the evolutionary history of body size change and historical patterns of
      colonization in the Cnemidophorus system. The phylogenetic analysis indicates
      that (i) oceanic islands have been founded at least five times from mainland
      sources by relatives of either C. tigris or C. hyperythrus, (ii) there have been
      two separate instances of character relaxation on oceanic islands for C. tigris,
      and (iii) there has been colonization of the oceanic island Cerralvo with
      retention of ancestral size for Cnemidophorus ceralbensis, a relative of C.
      hyperythrus. Finally, the phylogenetic analysis reveals potential cryptic species
      within mainland populations of C. tigris.

PMID- 9275193
TI  - Sex-specific quantitative trait loci affecting longevity in Drosophila
      melanogaster.
AB  - Senescence, the decline in survivorship and fertility with increasing age, is a
      near-universal property of organisms. Senescence and limited lifespan are thought
      to arise because weak natural selection late in life allows the accumulation of
      mutations with deleterious late-age effects that are either neutral (the mutation
      accumulation hypothesis) or beneficial (the antagonistic pleiotropy hypothesis)
      early in life. Analyses of Drosophila spontaneous mutations, patterns of
      segregating variation and covariation, and lines selected for late-age fertility
      have implicated both classes of mutation in the evolution of aging, but neither
      their relative contributions nor the properties of individual loci that cause
      aging in nature are known. To begin to dissect the multiple genetic causes of
      quantitative variation in lifespan, we have conducted a genome-wide screen for
      quantitative trait loci (QTLs) affecting lifespan that segregate among a panel of
      recombinant inbred lines using a dense molecular marker map. Five autosomal QTLs
      were mapped by composite interval mapping and by sequential multiple marker
      analysis. The QTLs had large sex-specific effects on lifespan and age-specific
      effects on survivorship and mortality and mapped to the same regions as candidate
      genes with fertility, cellular aging, stress resistance and male-specific
      effects. Late age-of-onset QTL effects are consistent with the mutation
      accumulation hypothesis for the evolution of senescence, and sex-specific QTL
      effects suggest a novel mechanism for maintaining genetic variation for lifespan.

PMID- 9275195
TI  - A screen for fast evolving genes from Drosophila.
AB  - In an attempt to quantify the rates of protein sequence divergence in Drosophila,
      we have devised a screen to differentiate between slow and fast evolving genes.
      We find that over one-third of randomly drawn cDNAs from a Drosophila
      melanogaster library do not cross-hybridize with Drosophila virilis DNA,
      indicating that they evolve with a very high rate. To determine the evolutionary
      characteristics of such protein sequences, we sequenced their homologs from a
      more closely related species (Drosophila yakuba). The amino acid substitution
      rates among these cDNAs are among the fastest known and several are only about 2
      fold lower than the corresponding values for silent substitutions. An analysis of
      within-species polymorphisms for one of these sequences reveals an exceptionally
      high number of polymorphic amino acid positions, indicating that the protein is
      not under strong negative selection. We conclude that the Drosophila genome
      harbors a substantial proportion of genes with a very high divergence rate.

PMID- 9275196
TI  - Operons and SL2 trans-splicing exist in nematodes outside the genus
      Caenorhabditis.
AB  - The genomes of most eukaryotes are composed of genes arranged on the chromosomes
      without regard to function, with each gene transcribed from a promoter at its 5'
      end. However, the genome of the free-living nematode Caenorhabditis elegans
      contains numerous polycistronic clusters similar to bacterial operons in which
      the genes are transcribed sequentially from a single promoter at the 5' end of
      the cluster. The resulting polycistronic pre-mRNAs are processed into
      monocistronic mRNAs by conventional 3' end formation, cleavage, and
      polyadenylation, accompanied by trans-splicing with a specialized spliced leader
      (SL), SL2. To determine whether this mode of gene organization and expression,
      apparently unique among the animals, occurs in other species, we have
      investigated genes in a distantly related free-living rhabditid nematode in the
      genus Dolichorhabditis (strain CEW1). We have identified both SL1 and SL2 RNAs in
      this species. In addition, we have sequenced a Dolichorhabditis genomic region
      containing a gene cluster with all of the characteristics of the C. elegans
      operons. We show that the downstream gene is trans-spliced to SL2. We also
      present evidence that suggests that these two genes are also clustered in the C.
      elegans and Caenorhabditis briggsae genomes. Thus, it appears that the
      arrangement of genes in operons pre-dates the divergence of the genus
      Caenorhabditis from the other genera in the family Rhabditidae, and may be more
      widespread than is currently appreciated.

PMID- 9275197
TI  - Dual roles for DNA sequence identity and the mismatch repair system in the
      regulation of mitotic crossing-over in yeast.
AB  - Sequence divergence acts as a potent barrier to homologous recombination; much of
      this barrier derives from an antirecombination activity exerted by mismatch
      repair proteins. An inverted repeat assay system with recombination substrates
      ranging in identity from 74% to 100% has been used to define the relationship
      between sequence divergence and the rate of mitotic crossing-over in yeast. To
      elucidate the role of the mismatch repair machinery in regulating recombination
      between mismatched substrates, we performed experiments in both wild-type and
      mismatch repair defective strains. We find that a single mismatch is sufficient
      to inhibit recombination between otherwise identical sequences, and that this
      inhibition is dependent on the mismatch repair system. Additional mismatches have
      a cumulative negative effect on the recombination rate. With sequence divergence
      of up to approximately 10%, the inhibitory effect of mismatches results mainly
      from antirecombination activity of the mismatch repair system. With greater
      levels of divergence, recombination is inefficient even in the absence of
      mismatch repair activity. In both wild-type and mismatch repair defective
      strains, an approximate log-linear relationship is observed between the
      recombination rate and the level of sequence divergence.

PMID- 9275198
TI  - Molecular keys to speciation: DNA polymorphism and the control of genetic
      exchange in enterobacteria.
AB  - Speciation involves the establishment of genetic barriers between closely related
      organisms. The extent of genetic recombination is a key determinant and a measure
      of genetic isolation. The results reported here reveal that genetic barriers can
      be established, eliminated, or modified by manipulating two systems which control
      genetic recombination, SOS and mismatch repair. The extent of genetic isolation
      between enterobacteria is a simple mathematical function of DNA sequence
      divergence. The function does not depend on hybrid DNA stability, but rather on
      the number of blocks of sequences identical in the two mating partners and
      sufficiently large to allow the initiation of recombination. Further, there is no
      obvious discontinuity in the function that could be used to define a level of
      divergence for distinguishing species.

PMID- 9275199
TI  - Changes of telomere length cause reciprocal changes in the lifespan of mother
      cells in Saccharomyces cerevisiae.
AB  - Budding yeast cells divide asymmetrically, giving rise to a mother and its
      daughter. Mother cells have a limited division potential, called their lifespan,
      which ends in proliferation-arrest and lysis. In this report we mutate telomerase
      in Saccharomyces cerevisiae to shorten telomeres and show that, rather than
      shortening lifespan, this leads to a significant extension in lifespan. This
      extension requires the product of the SIR3 gene, an essential component of the
      silencing machinery which binds to telomeres. In contrast, longer telomeres in a
      genotypically wild-type strain lead to a decrease in lifespan. These findings
      suggest that the length of telomeres dictates the lifespan by regulating the
      amount of the silencing machinery available to nontelomeric locations in the
      yeast genome.

PMID- 9275200
TI  - The protein product of the het-s heterokaryon incompatibility gene of the fungus
      Podospora anserina behaves as a prion analog.
AB  - The het-s locus of Podospora anserina is a heterokaryon incompatibility locus.
      The coexpression of the antagonistic het-s and het-S alleles triggers a lethal
      reaction that prevents the formation of viable heterokaryons. Strains that
      contain the het-s allele can display two different phenotypes, [Het-s] or [Het
      s*], according to their reactivity in incompatibility. The detection in these
      phenotypically distinct strains of a protein expressed from the het-s gene
      indicates that the difference in reactivity depends on a posttranslational
      difference between two forms of the polypeptide encoded by the het-s gene. This
      posttranslational modification does not affect the electrophoretic mobility of
      the protein in SDS/PAGE. Several results suggest a similarity of behavior between
      the protein encoded by the het-s gene and prions. The [Het-s] character can
      propagate in [Het-s*] strains as an infectious agent, producing a [Het-s*] -->
      [Het-s] transition, independently of protein synthesis. Expression of the [Het-s]
      character requires a functional het-s gene. The protein present in [Het-s]
      strains is more resistant to proteinase K than that present in [Het-s*] mycelium.
      Furthermore, overexpression of the het-s gene increases the frequency of the
      transition from [Het-s*] to [Het-s]. We propose that this transition is the
      consequence of a self-propagating conformational modification of the protein
      mediated by the formation of complexes between the two different forms of the
      polypeptide.

PMID- 9275201
TI  - Neuronal death in the central nervous system demonstrates a non-fibrin substrate
      for plasmin.
AB  - Mice deficient for plasminogen exhibit a variety of pathologies, all of which
      examined to date are reversed when the animals are also made fibrin(ogen)
      deficient. These results suggested that the predominant, and perhaps exclusive,
      physiological role of plasminogen is clearance of fibrin. Plasminogen-deficient
      mice also display resistance to excitotoxin-induced neurodegeneration, in
      contrast with wild-type mice, which are sensitive. Based on the genetic
      interaction between plasminogen and fibrinogen, we investigated whether
      resistance to neuronal cell death in the plasminogen-deficient mice is dependent
      on fibrin(ogen). Unexpectedly, mice lacking both plasminogen and fibrinogen are
      resistant to neurodegeneration to levels comparable to plasminogen-deficient
      mice. Therefore, plasmin acts on substrates other than fibrin during experimental
      neuronal degeneration, and may function similarly in other pathological settings
      in the central nervous system.

PMID- 9275202
TI  - smg mutants affect the expression of alternatively spliced SR protein mRNAs in
      Caenorhabditis elegans.
AB  - The expression of alternatively spliced mRNAs from genes is an ubiquitous
      phenomenon in metazoa. A screen for trans-acting factors that alter the
      expression of alternatively spliced mRNAs reveals that the smg genes of
      Caenorhabditis elegans participate in this process. smg genes have been proposed
      to function in degradation of nonsense mutant mRNAs. Here we show that smg genes
      affect normal gene expression by modulating the levels of alternatively spliced
      SRp20 and SRp30b mRNAs. These SR genes contain alternatively spliced exons that
      introduce upstream stop codons. The effect of smg genes on SR transcripts is
      specific, because the gene encoding the catalytic subunit of the cAMP-dependent
      protein kinase, which also contains an alternatively spliced exon that introduces
      upstream stop codon, is not effected in a smg background. These results suggest
      that the levels of alternatively spliced mRNAs may, in part, be regulated by
      alternative mRNA stability.

PMID- 9275203
TI  - Barriers to recombination between closely related bacteria: MutS and RecBCD
      inhibit recombination between Salmonella typhimurium and Salmonella typhi.
AB  - Previous studies have shown that inactivation of the MutS or MutL mismatch repair
      enzymes increases the efficiency of homeologous recombination between Escherichia
      coli and Salmonella typhimurium and between S. typhimurium and Salmonella typhi.
      However, even in mutants defective for mismatch repair the recombination
      frequencies are 10(2)- to 10(3)-fold less than observed during homologous
      recombination between a donor and recipient of the same species. In addition, the
      length of DNA exchanged during transduction between S. typhimurium and S. typhi
      is less than in transductions between strains of S. typhimurium. In homeologous
      transductions, mutations in the recD gene increased the frequency of transduction
      and the length of DNA exchanged. Furthermore, in mutS recD double mutants the
      frequency of homeologous recombination was nearly as high as that seen during
      homologous recombination. The phenotypes of the mutants indicate that the gene
      products of mutS and recD act independently. Because S. typhimurium and S. typhi
      are approximately 98-99% identical at the DNA sequence level, the inhibition of
      recombination is probably not due to a failure of RecA to initiate strand
      exchange. Instead, these results suggest that mismatches act at a subsequent
      step, possibly by slowing the rate of branch migration. Slowing the rate of
      branch migration may stimulate helicase proteins to unwind rather than extend the
      heteroduplex and leave uncomplexed donor DNA susceptible to further degradation
      by RecBCD exonuclease.

PMID- 9275204
TI  - Tumor necrosis factor (TNF)-mediated kinase cascades: bifurcation of nuclear
      factor-kappaB and c-jun N-terminal kinase (JNK/SAPK) pathways at TNF receptor
      associated factor 2.
AB  - TNF-induced activation of the transcription factor NF-kappaB and the c-jun N
      terminal kinase (JNK/SAPK) requires TNF receptor-associated factor 2 (TRAF2). The
      NF-kappaB-inducing kinase (NIK) associates with TRAF2 and mediates TNF activation
      of NF-kappaB. Herein we show that NIK interacts with additional members of the
      TRAF family and that this interaction requires the conserved "WKI" motif within
      the TRAF domain. We also investigated the role of NIK in JNK activation by TNF.
      Whereas overexpression of NIK potently induced NF-kappaB activation, it failed to
      stimulate JNK activation. A kinase-inactive mutant of NIK was a dominant negative
      inhibitor of NF-kappaB activation but did not suppress TNF- or TRAF2-induced JNK
      activation. Thus, TRAF2 is the bifurcation point of two kinase cascades leading
      to activation of NF-kappaB and JNK, respectively.

PMID- 9275205
TI  - The Syk and ZAP-70 SH2-containing tyrosine kinases are implicated in pre-T cell
      receptor signaling.
AB  - An early stage in thymocyte development, after rearrangement of the beta chain
      genes of the T cell receptor (TCR), involves expression of the pre-TCR complex
      and accompanying differentiation of CD4(-)CD8(-) double negative (DN) cells to
      CD4(+)CD8(+) double positive (DP) cells. The ZAP-70 and Syk tyrosine kinases each
      contain two N-terminal SH2 domains that bind phosphorylated motifs in antigen
      receptor subunits and are implicated in pre-T receptor signaling. However, mice
      deficient in either ZAP-70 or Syk have no defect in the formation of DP
      thymocytes. Here we show that, in mice lacking both Syk and ZAP-70, DN thymocytes
      undergo beta chain gene rearrangement but fail to initiate clonal expansion and
      are incapable of differentiating into DP cells after expression of the pre-TCR.
      These data suggest that the ZAP-70 and Syk tyrosine kinases have crucial but
      overlapping functions in signaling from the pre-TCR and hence in early thymocyte
      development.

PMID- 9275206
TI  - Frequency of HLA allele-specific peptide motifs in HIV-1 proteins correlates with
      the allele's association with relative rates of disease progression after HIV-1
      infection.
AB  - An HLA allele-specific cytotoxic T lymphocyte response is thought to influence
      the rate of disease progression in HIV-1-infected individuals. In a prior study
      of 139 HIV-1-infected homosexual men, we identified HLA class I alleles and
      observed an association of specific alleles with different relative hazards for
      progression to AIDS. Seeking an explanation for this association, we searched HIV
      1 protein sequences to determine the number of peptides matching motifs defined
      by combinations of specific amino acids reported to bind 16 class I alleles.
      Analyzing complete sequences of 12 clade B HIV isolates, we determined the number
      of allele motifs that were conserved (occurring in all 12 isolates) and
      nonconserved (occurring in only one isolate), as well as the average number of
      allele motifs per isolate. We found significant correlations with an allele's
      association with disease progression for counts of conserved motifs in gag (R =
      0.73; P = 0.002), pol (R = 0.58, P = 0.024), gp120 (R = 0.78, P = 0.00056), and
      total viral protein sequences (R = 0.67, P = 0.0058) and also for counts of
      nonconserved motifs in gag (R = 0.62, P = 0.013), pol (R = 0.74, P = 0.0017),
      gp41 (R = 0.52, P = 0.046), and total viral protein (R = 0.71, P = 0.0033). We
      also found significant correlations for the average number of motifs per isolate
      for gag, pol, gp120, and total viral protein. This study provides a plausible
      functional explanation for the observed association of different HLA alleles with
      variable rates of disease progression.

PMID- 9275207
TI  - Expression of adenoviral E3 transgenes in beta cells prevents autoimmune
      diabetes.
AB  - The adenovirus (Ad) genome contains immunoregulatory and cytokine inhibitory
      genes that are presumed to function in facilitating acute infection or in
      establishing persistence in vivo. Some of these genes are clustered in early
      region 3 (E3), which contains a 19-kDa glycoprotein (gp19) that inhibits the
      transport of selected class I major histocompatibility complex (MHC) molecules
      out of the endoplasmic reticulum. In addition, the E3 region contains three
      protein inhibitors of the cytolytic function of tumor necrosis factor alpha (TNF
      alpha). Because type I autoimmune diabetes destroys islets by mechanisms that
      involve class I MHC and TNF-alpha, we investigated whether the entire cassette of
      Ad E3 genes might prevent the onset of diabetes in a well studied lymphocytic
      choriomeningitis viral (LCMV) murine model of virus-induced autoimmune diabetes.
      In this model, a LCMV polypeptide (either glycoprotein or nucleoprotein)
      expressed as a transgene in the islets is a target for autoimmune destruction of
      beta cells after LCMV infection. In this scenario the LCMV-induced immune
      response is directed not only against the virus but also against the LCMV
      transgenes expressed in the beta cells. Our experiments demonstrated a very
      efficient prevention of this LCMV-triggered diabetes by the Ad E3 genes. This
      resulted from the inhibition of target cell recognition by a fully competent and
      LCMV-primed immune system. Unlike the results from the beta-2 microglobulin gene
      deletion experiments, our approach shows that selective regulation at the level
      of the target cell is sufficient to prevent autoimmune diabetes without
      disrupting the function of the systemic immune response. Although the Ad genes in
      these experiments were provided as transgenes, recent experiments may permit the
      introduction of such genes through the use of viral vectors. Although the
      decrease in class I MHC in islets by Ad genes was demonstrated in these in vivo
      studies, the relative importance of this process and the control of TNF-alpha
      cytolysis must await further genetic dissection of the introduced Ad genes.

PMID- 9275208
TI  - Tumor necrosis factor alpha plays a central role in immune-mediated clearance of
      adenoviral vectors.
AB  - Adenovirus (Ad) gene transfer vectors are rapidly cleared from infected
      hepatocytes in mice. To determine which effector mechanisms are responsible for
      elimination of the Ad vectors, we infected mice that were genetically compromised
      in immune effector pathways [perforin, Fas, or tumor necrosis factor alpha (TNF
      alpha)] with the Ad vector, Ad5-chloramphenicol acetyl transferase (CAT). Mice
      were sacrificed at 7-60 days postinfection, and the levels of CAT expression in
      the liver determined by a quantitative enzymatic assay. When the livers of
      infected mice were harvested 28 days postinfection, the levels of CAT expression
      revealed that the effectors most important for the elimination of the Ad vector
      were TNF-alpha > Fas > perforin. TNF-alpha did not have a curative effect on
      infected hepatocytes, as the administration of TNF-alpha to infected severe
      combined immunodeficient mice or to infected cultures in vitro had no specific
      effect on virus persistence. However, TNF-alpha-deficient mice demonstrated a
      striking reduction in the leukocytic infiltration early on in the infection,
      suggesting that TNF-alpha deficiency resulted in impaired recruitment of
      inflammatory cells to the site of inflammation. In addition, the TNF-deficient
      mice had a significantly reduced humoral immune response to virus infection.
      These results demonstrate a dominant role of TNF-alpha in elimination of Ad gene
      transfer vectors. This result is particularly important because viral proteins
      that disable TNF-alpha function have been removed from most Ad vectors, rendering
      them highly susceptible to TNF-alpha-mediated elimination.

PMID- 9275209
TI  - Delayed loss of cholesterol from a localized lipoprotein depot in apolipoprotein
      A-I-deficient mice.
AB  - The anti-atherogenic role of high density lipoprotein is well known even though
      the mechanism has not been established. In this study, we have used a novel model
      system to test whether removal of lipoprotein cholesterol from a localized depot
      will be affected by apolipoprotein A-I (apo A-I) deficiency. We compared the
      egress of cholesterol injected in the form of cationized low density lipoprotein
      into the rectus femoris muscle of apo A-I K-O and control mice. When the injected
      lipoprotein had been labeled with [3H]cholesterol, the t1/2 of labeled
      cholesterol loss from the muscle was about 4 days in controls and more than 7
      days in apo A-I K-O mice. The loss of cholesterol mass had an initial slow (about
      4 days) and a later more rapid component; after day 4, the disappearance curves
      for apo A-I K-O and controls began to diverge, and by day 7, the loss of injected
      cholesterol was significantly slower in apo A-I K-O than in controls. The
      injected lipoprotein cholesterol is about 70% in esterified form and undergoes
      hydrolysis, which by day 4 was similar in control and apo A-I K-O mice. The
      efflux potential of serum from control and apo A-I K-O mice was studied using
      media containing 2% native or delipidated serum. A significantly lower efflux of
      [3H]cholesterol from macrophages was found with native and delipidated serum from
      apo A-I K-O mice. In conclusion, these findings show that lack of apo A-I results
      in a delay in cholesterol loss from a localized depot in vivo and from
      macrophages in culture. These results provide support for the thesis that anti
      atherogenicity of high density lipoprotein is related in part to its role in
      cholesterol removal.

PMID- 9275210
TI  - HIV-1 infection of nondividing cells through the recognition of integrase by the
      importin/karyopherin pathway.
AB  - The karyophilic properties of the HIV-1 nucleoprotein complex facilitate
      infection of nondividing cells such as macrophages and quiescent T lymphocytes,
      and allow the in vivo delivery of transgenes by HIV-derived retroviral vectors
      into terminally differentiated cells such as neurons. Although the viral matrix
      (MA) and Vpr proteins have previously been shown to play important roles in this
      process, we demonstrate here that integrase, the enzyme responsible for mediating
      the integration of the viral genome in the host cell chromosome, can suffice to
      connect the HIV-1 preintegration complex with the cell nuclear import machinery.
      This novel function of integrase reflects the recognition of an atypical
      bipartite nuclear localization signal by the importin/karyopherin pathway.

PMID- 9275211
TI  - Targeted ablation of the vitamin D receptor: an animal model of vitamin D
      dependent rickets type II with alopecia.
AB  - Vitamin D, the major steroid hormone that controls mineral ion homeostasis,
      exerts its actions through the vitamin D receptor (VDR). The VDR is expressed in
      many tissues, including several tissues not thought to play a role in mineral
      metabolism. Studies in kindreds with VDR mutations (vitamin D-dependent rickets
      type II, VDDR II) have demonstrated hypocalcemia, hyperparathyroidism, rickets,
      and osteomalacia. Alopecia, which is not a feature of vitamin D deficiency, is
      seen in some kindreds. We have generated a mouse model of VDDR II by targeted
      ablation of the second zinc finger of the VDR DNA-binding domain. Despite known
      expression of the VDR in fetal life, homozygous mice are phenotypically normal at
      birth and demonstrate normal survival at least until 6 months. They become
      hypocalcemic at 21 days of age, at which time their parathyroid hormone (PTH)
      levels begin to rise. Hyperparathyroidism is accompanied by an increase in the
      size of the parathyroid gland as well as an increase in PTH mRNA levels. Rickets
      and osteomalacia are seen by day 35; however, as early as day 15, there is an
      expansion in the zone of hypertrophic chondrocytes in the growth plate. In
      contrast to animals made vitamin D deficient by dietary means, and like some
      patients with VDDR II, these mice develop progressive alopecia from the age of 4
      weeks.

PMID- 9275212
TI  - Expansion in vitro of transplantable human cord blood stem cells demonstrated
      using a quantitative assay of their lympho-myeloid repopulating activity in
      nonobese diabetic-scid/scid mice.
AB  - Human hematopoiesis originates in a population of stem cells with transplantable
      lympho-myeloid reconstituting potential, but a method for quantitating such cells
      has not been available. We now describe a simple assay that meets this need. It
      is based on the ability of sublethally irradiated immunodeficient nonobese
      diabetic-scid/scid (NOD/SCID) mice to be engrafted by intravenously injected
      human hematopoietic cells and uses limiting dilution analysis to measure the
      frequency of human cells that produce both CD34(-)CD19(+) (B-lymphoid) and
      CD34(+) (myeloid) colony-forming cell progeny in the marrow of such recipients 6
      to 8 weeks post-transplant. Human cord blood (CB) contains approximately 5 of
      these competitive repopulating units (CRU) per ml that have a similar
      distribution between the CD38(-) and CD38(+) subsets of CD34(+) CB cells as long
      term culture-initiating cells (LTC-IC) (4:1 vs. 2:1). Incubation of purified
      CD34(+)CD38(-) human CB cells in serum-free medium containing flt-3 ligand, Steel
      factor, interleukin 3, interleukin 6, and granulocyte colony-stimulating factor
      for 5-8 days resulted in a 100-fold expansion of colony-forming cells, a 4-fold
      expansion of LTC-IC, and a 2-fold (but significant, P < 0.02) increase in CRU.
      The culture-derived CRU, like the original CB CRU, generated pluripotent,
      erythroid, granulopoietic, megakaryopoietic, and pre-B cell progeny upon
      transplantation into NOD/SCID mice. These findings demonstrate an equivalent
      phenotypic heterogeneity amongst human CB cells detectable as CRU and LTC-IC. In
      addition, their similarly modest response to stimulation by a combination of
      cytokines that extensively amplify LTC-IC from normal adult marrow underscores
      the importance of ontogeny-dependent changes in human hematopoietic stem cell
      proliferation and self-renewal.

PMID- 9275213
TI  - The CXC chemokine stromal cell-derived factor 1 is not responsible for CD8+ T
      cell suppression of syncytia-inducing strains of HIV-1.
AB  - Primary CD8+ T cells from HIV+ asymptomatics can suppress virus production from
      CD4(+) T cells acutely infected with either non-syncytia-inducing (NSI) or
      syncytia-inducing (SI) HIV-1 isolates. NSI strains of HIV-1 predominantly use the
      CCR5 chemokine receptor as a fusion cofactor, whereas fusion of T cell line
      adapted SI isolates is mediated by another chemokine receptor, CXCR4. The CCR5
      ligands RANTES (regulated on activation, normal T cell expressed and secreted),
      macrophage inflammatory protein 1alpha (MIP-1alpha), and MIP-1beta are HIV-1
      suppressive factors secreted by CD8+ cells that inhibit NSI viruses. Recently,
      the CXC chemokine stromal cell-derived factor 1 (SDF-1) was identified as a
      ligand for CXCR4 and shown to inhibit SI strains. We speculated that SDF-1 might
      be an effector molecule for CD8+ suppression of SI isolates and assessed several
      SDF-1 preparations for inhibition of HIV-1LAI-mediated cell-cell fusion, and
      examined levels of SDF-1 transcripts in CD8(+) T cells. SDF-1 fusion inhibitory
      activity correlated with the N terminus, and the alpha and beta forms of SDF-1
      exhibited equivalent fusion blocking activity. SDF-1 preparations having the N
      terminus described by Bleul et al. (Bleul, C.C., Fuhlbrigge, R.C., Casasnovas,
      J.M., Aiuti, A. & Springer, T.A. (1996) J. Exp. Med. 184, 1101-1109) readily
      blocked HIV-1LAI-mediated fusion, whereas forms containing two or three
      additional N-terminal amino acids lacked this activity despite their ability to
      bind and/or signal through CXCR4. Though SDF-1 is constitutively expressed in
      most tissues, CD8 T cells contained extremely low levels of SDF-1 mRNA
      transcripts (<1 transcript/5,000 cells), and these levels did not correlate with
      virus suppressive activity. We conclude that suppression of SI strains of HIV-1
      by CD8+ T cells is unlikely to involve SDF-1.

PMID- 9275214
TI  - Evidence for rapid disappearance of initially expanded HIV-specific CD8+ T cell
      clones during primary HIV infection.
AB  - Down-regulation of the initial burst of viremia during primary HIV infection is
      thought to be mediated predominantly by HIV-specific cytotoxic T lymphocytes, and
      the appearance of this response is associated with major perturbations of the T
      cell receptor repertoire. Changes in the T cell receptor repertoire of virus
      specific cytotoxic T lymphocytes were analyzed in patients with primary infection
      to understand the failure of the cellular immune response to control viral spread
      and replication. This analysis demonstrated that a significant number of HIV
      specific T cell clones involved in the primary immune response rapidly
      disappeared. The disappearance was not the result of mutations in the virus
      epitopes recognized by these clones. Evidence is provided that phenomena such as
      high-dose tolerance or clonal exhaustion might be involved in the disappearance
      of these monoclonally expanded HIV-specific cytotoxic T cell clones. These
      findings should provide insights into how HIV, and possibly other viruses, elude
      the host immune response during primary infection.

PMID- 9275215
TI  - Biochemical changes in the frontal lobe of HIV-infected individuals detected by
      magnetic resonance spectroscopy.
AB  - We have developed a proton magnetic resonance spectroscopy method that
      selectively can sample cortical gray matter and adjacent white matter in the
      frontal lobe. We have used this approach to study a group of patients (n = 7)
      infected with HIV and clinical manifestations of the AIDS dementia complex (ADC),
      a group of patients (n = 8) infected with HIV without any indications of ADC, and
      seven controls. The patients without ADC had a statistically significant increase
      in the ratio of myo-inositol to creatine in white matter compared with normal
      controls. In contrast, the group of patients with ADC had almost normal levels of
      myo-inositol to creatine in both gray matter and white matter and showed a
      statistically significant decrease in the N-acetylaspartate to creatine ratio in
      gray matter compared with either the normal controls or the patients without ADC.
      Patterns of spectral abnormalities correlated with neuropsychological measures of
      frontal lobe dysfunction, suggesting that the evaluation of frontal lobe
      metabolism by magnetic resonance spectroscopy can play a role in the early
      detection of ADC, in determining its progression, and in assessing responses to
      therapeutic interventions.

PMID- 9275216
TI  - A novel virus in swine is closely related to the human hepatitis E virus.
AB  - A novel virus, designated swine hepatitis E virus (swine HEV), was identified in
      pigs. Swine HEV crossreacts with antibody to the human HEV capsid antigen. Swine
      HEV is a ubiquitous agent and the majority of swine >/=3 months of age in herds
      from the midwestern United States were seropositive. Young pigs naturally
      infected by swine HEV were clinically normal but had microscopic evidence of
      hepatitis, and developed viremia prior to seroconversion. The entire ORFs 2 and 3
      were amplified by reverse transcription-PCR from sera of naturally infected pigs.
      The putative capsid gene (ORF2) of swine HEV shared about 79-80% sequence
      identity at the nucleotide level and 90-92% identity at the amino acid level with
      human HEV strains. The small ORF3 of swine HEV had 83-85% nucleotide sequence
      identity and 77-82% amino acid identity with human HEV strains. Phylogenetic
      analyses showed that swine HEV is closely related to, but distinct from, human
      HEV strains. The discovery of swine HEV not only has implications for HEV vaccine
      development, diagnosis, and biology, but also raises a potential public health
      concern for zoonosis or xenozoonosis following xenotransplantation with pig
      organs.

PMID- 9275217
TI  - Iron accumulation in Alzheimer disease is a source of redox-generated free
      radicals.
AB  - Damage from free radicals has been demonstrated in susceptible neuronal
      populations in cases of Alzheimer disease. In this study, we investigated whether
      iron, a potent source of the highly reactive hydroxyl radical that is generated
      by the Fenton reaction with H2O2, might contribute to the source of radicals in
      Alzheimer disease. We found, using a modified histochemical technique that relies
      on the formation of mixed valence iron complexes, that redox-active iron is
      associated with the senile plaques and neurofibrillary tangles-the pathological
      hallmark lesions of this disease. This lesion-associated iron is able to
      participate in in situ oxidation and readily catalyzes an H2O2-dependent
      oxidation. Furthermore, removal of iron was completely effected using
      deferoxamine, after which iron could be rebound to the lesions. Characterization
      of the iron-binding site suggests that binding is dependent on available
      histidine residues and on protein conformation. Taken together, these findings
      indicate that iron accumulation could be an important contributor toward the
      oxidative damage of Alzheimer disease.

PMID- 9275218
TI  - Restricted structural gene polymorphism in the Mycobacterium tuberculosis complex
      indicates evolutionarily recent global dissemination.
AB  - One-third of humans are infected with Mycobacterium tuberculosis, the causative
      agent of tuberculosis. Sequence analysis of two megabases in 26 structural genes
      or loci in strains recovered globally discovered a striking reduction of silent
      nucleotide substitutions compared with other human bacterial pathogens. The lack
      of neutral mutations in structural genes indicates that M. tuberculosis is
      evolutionarily young and has recently spread globally. Species diversity is
      largely caused by rapidly evolving insertion sequences, which means that mobile
      element movement is a fundamental process generating genomic variation in this
      pathogen. Three genetic groups of M. tuberculosis were identified based on two
      polymorphisms that occur at high frequency in the genes encoding catalase
      peroxidase and the A subunit of gyrase. Group 1 organisms are evolutionarily old
      and allied with M. bovis, the cause of bovine tuberculosis. A subset of several
      distinct insertion sequence IS6110 subtypes of this genetic group have IS6110
      integrated at the identical chromosomal insertion site, located between dnaA and
      dnaN in the region containing the origin of replication. Remarkably, study of
      approximately 6,000 isolates from patients in Houston and the New York City area
      discovered that 47 of 48 relatively large case clusters were caused by genotypic
      group 1 and 2 but not group 3 organisms. The observation that the newly emergent
      group 3 organisms are associated with sporadic rather than clustered cases
      suggests that the pathogen is evolving toward a state of reduced transmissability
      or virulence.

PMID- 9275219
TI  - Functional characterization of the C---C chemokine-like molecules encoded by
      molluscum contagiosum virus types 1 and 2.
AB  - Many viruses have evolved mechanisms for evading the host immune system by
      synthesizing proteins that interfere with the normal immune response. The
      poxviruses are among the most accomplished at deceiving their hosts' immune
      systems. The nucleotide sequence of the genome of the human cutaneous poxvirus,
      molluscum contagiosum virus (MCV) type 1, was recently reported to contain a
      region that resembles a human chemokine. We have cloned and expressed the
      chemokine-like genes from MCV type 1 and the closely related MCV type 2 to
      determine a potential role for these proteins in the viral life cycle. In
      monocyte chemotaxis assays, the viral proteins have no chemotactic activity but
      both viral proteins block the chemotactic response to the human chemokine,
      macrophage inflammatory protein (MIP)-1alpha. Like MIP-1alpha, both viral
      proteins also inhibit the growth of human hematopoietic progenitor cells, but the
      viral proteins are more potent in this activity than the human chemokine. These
      viral chemokines antagonize the chemotactic activity of human chemokines and have
      an inhibitory effect on human hematopoietic progenitor cells. We hypothesize that
      the inhibition of chemotaxis is an immune evasion function of these proteins
      during molluscum contagiosum virus infection. The significance of hematopoietic
      progenitor cell inhibition in viral pathogenesis is uncertain.

PMID- 9275220
TI  - Complementation of sporulation and motility defects in a prokaryote by a
      eukaryotic GTPase.
AB  - The complex prokaryote, Myxococcus xanthus, undergoes a program of multicellular
      development when starved for nutrients, culminating in sporulation. M. xanthus
      makes MglA, a 22-kDa, soluble protein that is required for both multicellular
      development and gliding motility. MglA is similar in sequence to the
      Saccharomyces cerevisiae SAR1 protein, a member of the Ras/Rab/Rho superfamily of
      small eukaryotic GTPases. The SAR1 gene, when integrated into the M. xanthus
      genome, complements the sporulation defect of a DeltamglA strain. A forward,
      second-site mutation on the M. xanthus chromosome, rpm, in combination with SAR1,
      restores fruiting body morphogenesis and gliding motility to a DeltamglA strain.
      The result that the rpm mutation suppresses the substitution of SAR1 for mglA
      suggests that Sar1p interacts with other M. xanthus proteins to control the
      motility-dependent aggregation of cells during development.

PMID- 9275221
TI  - A secreted Salmonella protein with homology to an avirulence determinant of plant
      pathogenic bacteria.
AB  - Bacterial pathogens have evolved sophisticated mechanisms to interact with their
      hosts. A specialized type III protein secretion system capable of translocating
      bacterial proteins into host cells has emerged as a central factor in the
      interaction between a variety of mammalian and plant pathogenic bacteria with
      their hosts. Here we describe AvrA, a novel target of the centisome 63 type III
      protein secretion system of Salmonella enterica. AvrA shares sequence similarity
      with YopJ of the animal pathogen Yersinia pseudotuberculosis and AvrRxv of the
      plant pathogen Xanthomonas campestris pv. vesicatoria. These proteins are the
      first examples of putative targets of type III secretion systems in animal and
      plant pathogenic bacteria that share sequence similarity. They may therefore
      constitute a novel family of effector proteins with related functions in the
      cross-talk of these pathogens with their hosts.

PMID- 9275222
TI  - Peropsin, a novel visual pigment-like protein located in the apical microvilli of
      the retinal pigment epithelium.
AB  - A visual pigment-like protein, referred to as peropsin, has been identified by
      large-scale sequencing of cDNAs derived from human ocular tissues. The
      corresponding mRNA was found only in the eye, where it is localized to the
      retinal pigment epithelium (RPE). Peropsin immunoreactivity, visualized by light
      and electron microscopy, localizes the protein to the apical face of the RPE, and
      most prominently to the microvilli that surround the photoreceptor outer
      segments. These observations suggest that peropsin may play a role in RPE
      physiology either by detecting light directly or by monitoring the concentration
      of retinoids or other photoreceptor-derived compounds.

PMID- 9275223
TI  - Autoradiographic characterization of [3H]-5-HT-moduline binding sites in rodent
      brain and their relationship to 5-HT1B receptors.
AB  - 5-HT-moduline is an endogenous tetrapeptide [Leu-Ser-Ala-Leu (LSAL)] that was
      first isolated from bovine brain tissue. To understand the physiological role of
      this tetrapeptide, we studied the localization of 5-HT-moduline binding sites in
      rat and mouse brains. Quantitative data obtained with a gaseous detector of beta
      particles (beta-imager) indicated that [3H]-5-HT-moduline bound specifically to
      rat brain sections with high affinity (Kd = 0.77 nM and Bmax = 0. 26 dpm/mm2).
      Using film autoradiography in parallel, we found that 5-HT-moduline binding sites
      were expressed in a variety of rat and mouse brain structures. In 5-HT1B receptor
      knock-out mice, the specific binding of [3H]-5-HT-moduline was not different from
      background labeling, indicating that 5-HT-moduline targets are exclusively
      located on the 5-HT1B receptors. Although the distribution of 5-HT-moduline
      binding sites was similar to that of 5-HT1B receptors, they did not overlap
      totally. Differences in distribution patterns were found in regions containing
      either high levels of 5-HT1B receptors such as globus pallidus and subiculum that
      were poorly labeled or in other regions such as dentate gyrus of hippocampus and
      cortex where the relative density of 5-HT-moduline binding sites was higher than
      that of 5-HT1B receptors. In conclusion, our data, based on autoradiographic
      localization, indicate that 5-HT-moduline targets are located on 5-HT1B receptors
      present both on 5-HT afferents and postsynaptic neurons. By interacting
      specifically with 5-HT1B receptors, this tetrapeptide may play a pivotal role in
      pathological states such as stress that involves the dysfunction of 5-HT
      neurotransmission.

PMID- 9275224
TI  - Similarities in normal and binocularly rivalrous viewing.
AB  - We report here a series of observations-most of which the reader can experience
      directly-showing that distinct components of patterned visual stimuli (orthogonal
      lines of a different hue) vary in perception as sets. Although less frequent and
      often less complete, these perceptual fluctuations in normal viewing are
      otherwise similar to the binocular rivalry experienced when incompatible scenes
      are presented dichoptically.

PMID- 9275225
TI  - A signaling organelle containing the nerve growth factor-activated receptor
      tyrosine kinase, TrkA.
AB  - The topology of signal transduction is particularly important for neurons.
      Neurotrophic factors such as nerve growth factor (NGF) interact with receptors at
      distal axons and a signal is transduced by retrograde transport to the cell body
      to ensure survival of the neuron. We have discovered an organelle that may
      account for the retrograde transport of the neurotrophin signal. This organelle
      is derived from endocytosis of the receptor tyrosine kinase for NGF, TrkA. In
      vitro reactions containing semi-intact PC12 cells and ATP were used to enhance
      recovery of a novel organelle: small vesicles containing internalized NGF bound
      to activated TrkA. These vesicles were distinct from clathrin coated vesicles,
      uncoated primary endocytic vesicles, and synaptic vesicles, and resembled
      transport vesicles in their sedimentation velocity. They contained 10% of the
      total bound NGF and almost one-third of the total tyrosine phosphorylated TrkA.
      These small vesicles are compelling candidates for the organelles through which
      the neurotrophin signal is conveyed down the axon.

PMID- 9275227
TI  - Inactivation of the survival motor neuron gene, a candidate gene for human spinal
      muscular atrophy, leads to massive cell death in early mouse embryos.
AB  - Proximal spinal muscular atrophy is an autosomal recessive human disease of
      spinal motor neurons leading to muscular weakness with onset predominantly in
      infancy and childhood. With an estimated heterozygote frequency of 1/40 it is the
      most common monogenic disorder lethal to infants; milder forms represent the
      second most common pediatric neuromuscular disorder. Two candidate genes-survival
      motor neuron (SMN) and neuronal apoptosis inhibitory protein have been identified
      on chromosome 5q13 by positional cloning. However, the functional impact of these
      genes and the mechanism leading to a degeneration of motor neurons remain to be
      defined. To analyze the role of the SMN gene product in vivo we generated SMN
      deficient mice. In contrast to the human genome, which contains two copies, the
      mouse genome contains only one SMN gene. Mice with homozygous SMN disruption
      display massive cell death during early embryonic development, indicating that
      the SMN gene product is necessary for cellular survival and function.

PMID- 9275226
TI  - Neuronal nicotinic threonine-for-leucine 247 alpha7 mutant receptors show
      different gating kinetics when activated by acetylcholine or by the
      noncompetitive agonist 5-hydroxytryptamine.
AB  - Mutation of the highly conserved leucine residue (Leu-247) converts 5
      hydroxytryptamine (5HT) from an antagonist into an agonist of neuronal homomeric
      alpha7 nicotinic acetylcholine receptor expressed in Xenopus oocytes. We show
      here that acetylcholine (AcCho) activates two classes of single channels with
      conductances of 44 pS and 58 pS, similar to those activated by 5HT. However, the
      mean open time of AcCho-gated ion channels (11 ms) is briefer than that of 5HT
      gated ion channels (18 ms). Furthermore, whereas the open time of AcCho channels
      lengthens with hyperpolarization, that of 5HT channels is decreased. In voltage
      clamped oocytes, the apparent affinity of the alpha7 mutant receptor for 5HT is
      not modified by the presence of dihydro-beta-erythroidine, which acts on the
      AcCho binding site in a competitive manner. This indicates a noncompetitive
      action of 5HT on nicotinic acetylcholine receptors. Considered together, our
      findings show that AcCho gates alpha7 mutant channels with similar conductance
      but with different kinetic profile than the channels gated by 5HT, suggesting
      that the two agonists act on different docking sites. These results will help to
      understand the crosstalk between cholinergic and serotonergic systems in the
      central nervous system.

PMID- 9275228
TI  - Cell surface expression of the Alzheimer disease-related presenilin proteins.
AB  - The presenilin proteins PS-1 and PS-2 are crucially involved in Alzheimer disease
      (AD), but their molecular functions are not known. They are integral membrane
      proteins, but whether they can be expressed at the surface of cells has been in
      dispute. Here we show by immunofluorescence experiments, using anti-peptide
      antibodies specific for either PS-1 or PS-2, that live cultured DAMI cells and
      differentiated human NT2N neuronal cells are specifically immunolabeled for their
      endogenous as well as transfected presenilins, although the cells cannot be
      immunolabeled for their intracellular tubulin, unless they are first fixed and
      permeabilized. These and other results establish that portions of the presenilins
      are indeed expressed at the surfaces of these cells. These findings support our
      previous proposal that the presenilins on the surface of a cell engage in
      intercellular interactions with the beta-amyloid precursor protein on the surface
      of a neighboring cell, as a critical step in the molecular and cellular
      mechanisms that lead to AD.

PMID- 9275229
TI  - Modulation of potassium channel function by methionine oxidation and reduction.
AB  - Oxidation of amino acid residues in proteins can be caused by a variety of
      oxidizing agents normally produced by cells. The oxidation of methionine in
      proteins to methionine sulfoxide is implicated in aging as well as in
      pathological conditions, and it is a reversible reaction mediated by a ubiquitous
      enzyme, peptide methionine sulfoxide reductase. The reversibility of methionine
      oxidation suggests that it could act as a cellular regulatory mechanism although
      no such in vivo activity has been demonstrated. We show here that oxidation of a
      methionine residue in a voltage-dependent potassium channel modulates its
      inactivation. When this methionine residue is oxidized to methionine sulfoxide,
      the inactivation is disrupted, and it is reversed by coexpression with peptide
      methionine sulfoxide reductase. The results suggest that oxidation and reduction
      of methionine could play a dynamic role in the cellular signal transduction
      process in a variety of systems.

PMID- 9275230
TI  - VMAT2 knockout mice: heterozygotes display reduced amphetamine-conditioned
      reward, enhanced amphetamine locomotion, and enhanced MPTP toxicity.
AB  - The brain vesicular monoamine transporter (VMAT2) pumps monoamine
      neurotransmitters and Parkinsonism-inducing dopamine neurotoxins such as 1-methyl
      4-phenyl-phenypyridinium (MPP+) from neuronal cytoplasm into synaptic vesicles,
      from which amphetamines cause their release. Amphetamines and MPP+ each also act
      at nonvesicular sites, providing current uncertainties about the contributions of
      vesicular actions to their in vivo effects. To assess vesicular contributions to
      amphetamine-induced locomotion, amphetamine-induced reward, and sequestration and
      resistance to dopaminergic neurotoxins, we have constructed transgenic VMAT2
      knockout mice. Heterozygous VMAT2 knockouts are viable into adult life and
      display VMAT2 levels one-half that of wild-type values, accompanied by smaller
      changes in monoaminergic markers, heart rate, and blood pressure. Weight gain,
      fertility, habituation, passive avoidance, and locomotor activities are similar
      to wild-type littermates. In these heterozygotes, amphetamine produces enhanced
      locomotion but diminished behavioral reward, as measured by conditioned place
      preference. Administration of the MPP+ precursor N-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine to heterozygotes produces more than twice the dopamine cell
      losses found in wild-type mice. These mice provide novel information about the
      contributions of synaptic vesicular actions of monoaminergic drugs and
      neurotoxins and suggest that intact synaptic vesicle function may contribute more
      to amphetamine-conditioned reward than to amphetamine-induced locomotion.

PMID- 9275231
TI  - A model of ocular dominance column development by competition for trophic factor.
AB  - Recent experimental evidence has shown that application of certain neurotrophic
      factors (NTs) to the developing primary visual cortex prevents the development of
      ocular dominance (OD) columns. One interpretation of this result is that
      afferents from the lateral geniculate nucleus compete for postsynaptic trophic
      factor in an activity-dependent manner. Application of excess trophic factor
      eliminates this competition, thereby preventing OD column formation. We present a
      model of OD column development, incorporating Hebbian synaptic modification and
      activity-driven competition for NT, which accounts for both normal OD column
      development as well as the prevention of that development when competition is
      removed. In the "control" situation, when available NT is below a critical
      amount, OD columns form normally. These columns form without weight normalization
      procedures and in the presence of positive inter-eye correlations. In the
      "experimental" case, OD column development is prevented in a local neighborhood
      in which excess NT has been added. Our model proposes a biologically plausible
      mechanism for competition between neural populations that is motivated by several
      pieces of experimental data, thereby accounting for both normal and
      experimentally perturbed conditions.

PMID- 9275232
TI  - Substitution of a mutant alpha2a-adrenergic receptor via "hit and run" gene
      targeting reveals the role of this subtype in sedative, analgesic, and anesthetic
      sparing responses in vivo.
AB  - Norepinephrine contributes to antinociceptive, sedative, and sympatholytic
      responses in vivo, and alpha2 adrenergic receptor (alpha2AR) agonists are used
      clinically to mimic these effects. Lack of subtype-specific agonists has
      prevented elucidation of the role that each alpha2AR subtype (alpha2A, alpha2B,
      and alpha2C) plays in these central effects. Here we demonstrate that alpha2AR
      agonist-elicited sedative, anesthetic-sparing, and analgesic responses are lost
      in a mouse line expressing a subtly mutated alpha2AAR, D79N alpha2AAR, created by
      two-step homologous recombination. These functional changes are accompanied by
      failure of the D79N alpha2AAR to inhibit voltage-gated Ca2+ currents and
      spontaneous neuronal firing, a measure of K+ current activation. These results
      provide definitive evidence that the alpha2AAR subtype is the primary mediator of
      clinically important central actions of alpha2AR agonists and suggest that the
      D79N alpha2AAR mouse may serve as a model for exploring other possible alpha2AAR
      functions in vivo.

PMID- 9275233
TI  - Spinophilin, a novel protein phosphatase 1 binding protein localized to dendritic
      spines.
AB  - Dendritic spines receive the vast majority of excitatory synaptic contacts in the
      mammalian brain and are presumed to contain machinery for the integration of
      various signal transduction pathways. Protein phosphatase 1 (PP1) is greatly
      enriched in dendritic spines and has been implicated in both the regulation of
      ionic conductances and long-term synaptic plasticity. The molecular mechanism
      whereby PP1 is localized to spines is unknown. We have now characterized a novel
      protein that forms a complex with the catalytic subunit of PP1 and is a potent
      modulator of PP1 enzymatic activity in vitro. Within the brain this protein
      displays a remarkably distinct localization to the heads of dendritic spines and
      has therefore been named spinophilin. Spinophilin has the properties expected of
      a scaffolding protein localized to the cell membrane and contains a single
      consensus sequence in PSD95/DLG/zo-1, which implies cross-linking of PP1 to
      transmembrane protein complexes. We propose that spinophilin represents a novel
      targeting subunit for PP1, which directs the enzyme to those substrates in the
      dendritic spine compartment, e.g., neurotransmitter receptors, which mediate the
      regulation of synaptic function by PP1.

PMID- 9275234
TI  - Loss of protein kinase C inhibition in the beta-T594M variant of the amiloride
      sensitive Na+ channel.
AB  - We previously reported the presence of a novel variant (beta-T594M) of the
      amiloride-sensitive Na+ channel (ASSC) in which the threonine residue at position
      594 in the beta-subunit has been replaced by a methionine residue.
      Electrophysiological studies of the ASSC on Epstein-Barr virus (EBV)-transformed
      lymphocytes carrying this variant showed that the 8-(4-chlorophenylthio)
      adenosine 3':5'-cyclic monophosphate (8cpt-cAMP)-induced responses were enhanced
      when compared to wild-type EBV-transformed lymphocytes. Furthermore, in wild-type
      EBV-transformed cells, the 8cpt-cAMP-induced response was totally blocked by the
      phorbol ester, phorbol 12-myristate 13-acetate (PMA). This inhibitory effect of
      PMA was blocked by a protein kinase C inhibitor, chelerythrine. We now have
      identified individuals who are homozygous for this variant, and showed that PMA
      had no effect on the 8cpt-cAMP-induced responses in the EBV-transformed
      lymphocytes from such individuals. Cells heterozygous for this variant showed
      mixed responses to PMA, with the majority of cells partially inhibited by PMA.
      Our results demonstrate that an alteration in a single amino acid residue in the
      beta-subunit of the ASSC can lead to a total loss of inhibition to PMA, and
      establish the beta-subunit as having an important role in conferring a regulatory
      effect on the ASSC of lymphocytes.

PMID- 9275235
TI  - Lipoxin A4 stable analogs inhibit leukocyte rolling and adherence in the rat
      mesenteric microvasculature: role of P-selectin.
AB  - Three different stable lipoxin A4 (LXA4) analogs (i.e., 16-phenoxy-LXA4-Me, 15
      cyclohexyl-LXA4-Me, and 15-R/S-methyl-LXA4-Me) were studied for their ability to
      modulate leukocyte-endothelial cell interactions in the rat mesenteric
      microvasculature. Superfusion of the rat mesentery with 50 micromol/liter NG
      nitro-L-arginine methyl ester (L-NAME) caused a significant, time-dependent
      increase in leukocyte rolling (56 +/- 8 cells/min; P < 0.01 vs. control) and
      leukocyte adherence (12.5 +/- 1. 2 cells/100 micron length of venule; P < 0.01
      vs. control) after 120 min of superfusion. Concomitant superfusion of the rat
      mesentery with 10 nmol/liter of each of three lipoxin analogs consistently and
      markedly attenuated L-NAME-induced leukocyte rolling to 10 +/- 4 (P < 0.01), 4 +/
      1 (P < 0.01), and 32 +/- 7 (P < 0.05) cells/min, and adherence to 4 +/- 0.8 (P <
      0.01), 1.1 +/- 0.4 (P < 0.01), and 7 +/- 0.7 (P < 0.05) cells/100 micron length
      of venule (16-phenoxy-LXA4-Me, 15-cyclohexyl-LXA4-Me, and 15-R/S- methyl-LXA4-Me,
      respectively). No alterations of systemic blood pressure or mesenteric venular
      shear rates were observed in any group. Immunohistochemical up-regulation of P
      selectin expression on intestinal venular endothelium was significantly increased
      (P < 0.01) after exposure to L-NAME, and this was significantly attenuated by
      these lipoxin analogs (P < 0.01). Thus, in vivo superfusion of the rat mesentery
      with stable lipoxin analogs at 10 nmol/liter reduces L-NAME-induced leukocyte
      rolling and adherence in the mesenteric rat microvasculature by attenuating P
      selectin expression. This anti-inflammatory mechanism may represent a novel and
      potent regulatory action of lipoxins on the immune system.

PMID- 9275236
TI  - F-actin and G-actin binding are uncoupled by mutation of conserved tyrosine
      residues in maize actin depolymerizing factor (ZmADF).
AB  - Actin depolymerizing factors (ADF) are stimulus responsive actin cytoskeleton
      modulating proteins. They bind both monomeric actin (G-actin) and filamentous
      actin (F-actin) and, under certain conditions, F-actin binding is followed by
      filament severing. In this paper, using mutant maize ADF3 proteins, we
      demonstrate that the maize ADF3 binding of F-actin can be spatially distinguished
      from that of G-actin. One mutant, zmadf3-1, in which Tyr-103 and Ala-104
      (equivalent to destrin Tyr-117 and Ala-118) have been replaced by phenylalanine
      and glycine, respectively, binds more weakly to both G-actin and F-actin compared
      with maize ADF3. A second mutant, zmadf3-2, in which both Tyr-67 and Tyr-70 are
      replaced by phenylalanine, shows an affinity for G-actin similar to maize ADF3,
      but F-actin binding is abolished. The two tyrosines, Tyr-67 and Tyr-70, are in
      the equivalent position to Tyr-82 and Tyr-85 of destrin, respectively. Using the
      tertiary structure of destrin, yeast cofilin, and Acanthamoeba actophorin, we
      discuss the implications of removing the aromatic hydroxyls of Tyr-82 and Tyr-85
      (i.e., the effect of substituting phenylalanine for tyrosine) and conclude that
      Tyr-82 plays a critical role in stabilizing the tertiary structure that is
      essential for F-actin binding. We propose that this tertiary structure is
      maintained as a result of a hydrogen bond between the hydroxyl of Tyr-82 and the
      carbonyl of Tyr-117, which is located in the long alpha-helix; amino acid
      components of this helix (Leu-111 to Phe-128) have been implicated in G-actin and
      F-actin binding. The structures of human destrin and yeast cofilin indicate a
      hydrogen distance of 2.61 and 2.77 A, respectively, with corresponding bond
      angles of 99.5 degrees and 113 degrees, close to the optimum for a strong
      hydrogen bond.

PMID- 9275238
TI  - The gene for albicidin detoxification from Pantoea dispersa encodes an esterase
      and attenuates pathogenicity of Xanthomonas albilineans to sugarcane.
AB  - Albicidin phytotoxins are pathogenicity factors in a devastating disease of
      sugarcane known as leaf scald, caused by Xanthomonas albilineans. A gene (albD)
      from Pantoea dispersa has been cloned and sequenced and been shown to code for a
      peptide of 235 amino acids that detoxifies albicidin. The gene shows no
      significant homology at the DNA or protein level to any known sequence, but the
      gene product contains a GxSxG motif that is conserved in serine hydrolases. The
      AlbD protein, purified to homogeneity by means of a glutathione S-transferase
      gene fusion system, showed strong esterase activity on p-nitrophenyl butyrate and
      released hydrophilic products during detoxification of albicidins. AlbD
      hydrolysis of p-nitrophenyl butyrate and detoxification of albicidins required no
      complex cofactors. Both processes were strongly inhibited by phenylmethylsulfonyl
      fluoride, a serine enzyme inhibitor. These data strongly suggest that AlbD is an
      albicidin hydrolase. The enzyme detoxifies albicidins efficiently over a pH range
      from 5.8 to 8.0, with a broad temperature optimum from 15 to 35 degrees C.
      Expression of albD in transformed X. albilineans strains abolished the capacity
      to release albicidin toxins and to incite disease symptoms in sugarcane. The gene
      is a promising candidate for transfer into sugarcane to confer a form of disease
      resistance.

PMID- 9275237
TI  - Expression of an ortholog of replication protein A1 (RPA1) is induced by
      gibberellin in deepwater rice.
AB  - Internodes of deepwater rice are induced to grow rapidly when plants become
      submerged. This adaptation enables deepwater rice to keep part of its foliage
      above the rising flood waters during the monsoon season and to avoid drowning.
      This growth response is, ultimately, elicited by the plant hormone gibberellin
      (GA). The primary target tissue for GA action is the intercalary meristem of the
      internode. Using differential display of mRNA, we have isolated a number of genes
      whose expression in the intercalary meristem is regulated by GA. The product of
      one of these genes was identified as an ortholog of replication protein A1
      (RPA1). RPA is a heterotrimeric protein involved in DNA replication,
      recombination, and repair and also in regulation of transcription. A chimeric
      construct, in which the single-stranded DNA-binding domain of rice RPA1 was
      spliced into the corresponding region of yeast RPA1, was able to complement a
      yeast rpa1 mutant. The transcript level of rice RPA1 is high in tissues
      containing dividing cells. RPA1 mRNA levels increase rapidly in the intercalary
      meristem during submergence and treatment with GA before the increase in the
      level of histone H3 mRNA, a marker for DNA replication.

PMID- 9275242
TI  - Men's career development and marriage timing during a period of rising
      inequality.
AB  - Based on data from 1979-1990 NLSY interviews, we investigate the implications of
      rising economic inequality for young men's marriage timing. Our approach is to
      relate marriage formation to the ease or difficulty of the career-entry process
      and to show that large race/schooling differences in career development lead to
      substantial variations in marriage timing. We develop measures of current career
      "maturity" and of long-term labor-market position. Employing discrete-time event
      history methods, we show that these variables have a substantial impact on
      marriage formation for both blacks and whites. Applying our regression results to
      models based on observed race/schooling patterns of career development, we then
      estimate cumulative proportions ever married in a difficult versus an easy career
      entry process. We find major differences in the pace of marriage formation,
      depending on the difficulty of the career transition. We also find considerable
      differences in these marriage timing patterns across race/schooling groups
      corresponding to the large observed differences in the speed and difficulty of
      career transition between and within these groups.

PMID- 9275243
TI  - Cohabiting partners' economic circumstances and marriage.
AB  - Past studies of the transition to marriage generally have relied on information
      about only one individual or have attempted to measure characteristics of
      potential spouses indirectly. Drawing on data from the two waves of the National
      Survey of Families and Households (NSFH), we examine the effects of economic
      circumstances of both partners in cohabiting unions on the transition to
      marriage. Focusing on both partners in a relationship affords a more direct test
      of the relative importance of men's versus women's economic circumstances. Our
      findings suggest that only the male partner's economic resources affect the
      transition to marriage, with positive economic situations accelerating marriage
      and deterring separation. Our results imply that despite trends toward
      egalitarian gender-role attitudes and increasing income provision among women,
      cohabiting men's economic circumstances carry far more weight than women's in
      marriage formation.

PMID- 9275245
TI  - Polygyny and reproductive behavior in sub-Saharan Africa: a contextual analysis.
AB  - In this paper I examine the effect of polygyny on aggregate reproductive
      behavior. I argue that within countries there exist different polygyny regimes,
      each exhibiting a unique reproductive pattern. Using the 1988/1989 Kenya
      Demographic and Health Survey (KDHS1) data, I identify three distinct regimes:
      low-polygyny, mid-polygyny, and high-polygyny regimes. The results of the
      bivariate and multivariate analyses reveal strong differences in reproductive
      preferences and behaviors across polygyny regimes. High-polygyny regimes, for
      instance, maintain a value orientation that favors and encourages high
      reproductive performance. The force of this pronatalism operates equally for men
      and women; but whereas men in this regime attain their reproductive goals by
      marrying multiple wives, women attain theirs by maximizing their reproductive
      capabilities. This maximization occurs through early initiation of
      sexual/reproductive activity, universal marriage and minimal interruption of
      marriage, nonuse of contraception within a union, and a positive attitude toward
      high fertility.

PMID- 9275244
TI  - Couple childbearing desires, intentions, and births.
AB  - Using new panel data from the National Surveys of Families and Households, I
      investigate the effects of wives' and husbands' childbearing desires on their
      spouses' intentions, and the effects of spouses' desires and intentions on
      subsequent births. The results show clearly that husbands' desires and intentions
      influence couples' births, with approximately equal force to that of wives'
      desires and intentions. When couples disagreed about wanting a child, each
      partners' intentions were shifted toward not having a child; and disagreement in
      desires or intentions were reflected in birth rates that were lower than average.
      These patterns were generally not different for couples with more or less
      traditional gender roles or attitudes.

PMID- 9275246
TI  - Learning in social networks and contraceptive choice.
AB  - A puzzling observation in the diffusion of modern fertility control is the
      persistent diversity in contraceptive practices across communities or social
      strata. I propose a model of "learning in social networks" to explain this
      diversity with the random dynamics of word-of-mouth communication. Women are
      uncertain about the merits of modern contraception and estimate the different
      qualities of available method based on imprecise information from network
      partners. Their contraceptive choices are determined by this estimate and by
      private knowledge about one's personal characteristics. This process of social
      learning leads to path-dependent adoption of fertility control within, and
      diversity in contraceptive practices across villages or social strata.

PMID- 9275247
TI  - Community-level determinants of contraceptive use in the Philippines: a
      structural analysis.
AB  - We use household and community data from the Philippines to estimate a multilevel
      model of contraceptive use. We go beyond previous efforts in this field by
      developing a structural model that recognizes joint endogeneity and the temporal
      ordering of variables. by considering a wider range of community influences on
      fertility behavior, and by employing an econometric procedure allowing for a
      multilevel error structure. The results suggest that there are significant
      effects on fertility behavior of community-level family planning services, labor
      conditions, and infrastructure development. These results provide insights
      regarding the structural determinants of contraceptive use and fertility that are
      useful for drawing policy implications.

PMID- 9275249
TI  - Estimating childhood mortality trends from routine data: a simulation using the
      preceding birth technique in Bangladesh.
AB  - The Preceding Birth Technique (PBT) has been proposed as a method suitable for
      ascertaining the prevailing level of under-2 mortality in countries without full
      vital registration. It is a monitoring tool rather than a method that will
      replace other established approaches to measuring childhood mortality levels and
      differentials that other demographers have developed over the last 30 years. The
      principle obstacle to the wider adoption of the PBT is the low proportion of
      women who give birth in maternity clinics and hospitals. A larger proportion of
      mothers, however, visit clinics and hospitals for antenatal care and to vaccinate
      their newborn. We used data from the Matlab surveillance system to test the
      accuracy of mortality estimates derived using the PBT with data obtained from
      mothers at antenatal visits and at the vaccination of their youngest children.
      The study shows that the PBT estimates under-3 rather than under-2 mortality in
      Bangladesh due to the long birth intervals. The data when used to stimulate the
      collection of the information at antenatal or postnatal visits, nonetheless
      provide an accurate description of under-3 mortality trends and differences for
      the two periods examined--before 1984 and before 1989.

PMID- 9275248
TI  - Premature birth and the changing composition of newborn infectious disease
      mortality: reconsidering "exogenous" mortality.
AB  - Linked death and birth records from San Antonio, Texas revealed that infectious
      infant mortality is increasingly a function of premature birth and low birth
      weight. Between 1935 and 1944, 4% of infectious infant deaths had associated
      causes involving prematurity and related conditions; by 1980, 25% of infectious
      infant deaths involved prematurity and more than 40% of those infants weighed
      less than 2,500 grams. The shift in birth-weight composition results almost
      entirely from an increase in very low-weight births. Under conditions of advanced
      perinatal technology, infectious infant mortality should no longer be viewed as
      wholly exogenous. These findings further undermine the contemporary relevance of
      the exogenous-endogenous distinction.

PMID- 9275250
TI  - Population momentum expresses population aging.
AB  - Population momentum and population aging occur when an initially growing
      population experiences a reduction in fertility to replacement level.
      Conceptually and empirically, momentum and aging express the same change, albeit
      on different scales. Fundamentally, they are two manifestations of the underlying
      process of demographic transformation. We consider three measures of aging over
      the transition to stationarity: the increase in mean population age, the decrease
      in the proportion under age 30, and the increase in the proportion over age 65.
      The three measures of aging are highly correlated, though the relationship to
      momentum is weakest for the increase in the proportion over age 65. We find that
      momentum is linearly related to aging. In both model and actual populations, a
      one-year increase in mean age translates into about 4.5% more population growth.
      The population below age 30 does not grow over the transition to stationarity and
      the ratio of initial to ultimate proportions under age 30 is virtually identical
      to momentum.

PMID- 9275251
TI  - Urban labor markets and individual transitions out of poverty.
AB  - Using data from the Panel Study of Income Dynamics and the U.S. census, I examine
      the effect of four structural characteristics on individual poverty exists: (1)
      economic restructuring, (2) skills mismatches, (3) racial residential
      segregation, and (4) welfare benefit levels. Results show that these factors play
      a role in explaining African Americans' economic disadvantages, but they have a
      weaker and often contrary impact on whites' poverty exists. Overall, the
      differing impact of the contextual characteristics on African Americans and
      whites exacerbates social stratification and illustrates racial divisions that
      contribute to pervade the labor market.

PMID- 9275252
TI  - Inhibition of milk ejection in cows by oxytocin receptor blockade, alpha
      adrenergic receptor stimulation and in unfamiliar surroundings.
AB  - Inhibition of milk ejection in cows by oxytocin receptor blockade (Atosiban) and
      alpha-adrenergic receptor stimulation (phenylephrine) prior to prestimulation was
      compared with inhibition of milk ejection in unfamiliar surroundings. In
      addition, Atosiban and phenylephrine were administered after a 1 min
      prestimulation or 1 min after the start of milking. Oxytocin concentrations
      increased during milking in all treatments. The spontaneously removed milk
      fraction (before oxytocin was injected) was similar for Atosiban and
      phenylephrine treatments and in unfamiliar surroundings, but lower than in
      controls. Peak flow rates were similar in all treatments, but reduced as compared
      with controls when phenylephrine and Atosiban were administered before
      prestimulation. Peripheral (Atosiban, phenylephrine) and central (unfamiliar
      surroundings) inhibition of milk ejection reduced the amount of available milk
      similarity. Drug treatments resulted in similar peak flow rates; however, teats
      were contracted after phenylephrine administration but not after Atosiban. The
      inhibition induced by Atosiban could be abolished by oxytocin injection, but not
      induced by phenylephrine, which was antagonized by alpha-adrenergic receptor
      blockade. These results indicate that inhibition of milk ejection through
      activation of alpha-adrenergic receptors is based on blockade of milk flow into
      the cistern, but not through the teats.

PMID- 9275253
TI  - Oxytocin and prolactin suppress cortisol responses to acute stress in both
      lactating and non-lactating sheep.
AB  - Cortisol response to stress appears to differ between lactating and non-lactating
      animals. Lactating (14 d post partum) and non-lactating sheep were fitted with
      probes so that drugs and hormones could be infused directly into the posterior
      pituitary and paraventricular nucleus of the hypothalamus. The animals were also
      fitted with instruments to allow monitoring of heart rate, body temperature and
      blood cortisol levels. Their reactions to a source of acute stress (a barking
      dog) were then followed, with or without drug and hormone manipulation. Results
      in both lactating and non-lactating animals indicated shortcomings in the use of
      cortisol as a stress indicator. Infusing prolactin and oxytocin into either the
      posterior pituitary or the paraventricular nucleus of the hypothalamus suppressed
      cortisol responsiveness to stress in both lactating and non-lactating animals
      (the latter to a greater extent). In the absence of drugs, lactating animals had
      a slightly higher basal level of cortisol and a lower cortisol response to stress
      than their non-lactating counterparts. Despite suppression of cortisol responses,
      with or without drugs, other indicators of stress still changed with the presence
      of a barking dog, suggesting the complexity of control involved in stress
      responses.

PMID- 9275254
TI  - Non-insulin- and insulin-mediated glucose uptake in dairy cows.
AB  - Four mid-lactation Holstein dairy cows (mean milk yield on day of experiments
      26.1 kg/d) were used in a series of experiments to establish the contribution of
      non-insulin-mediated glucose uptake to total glucose uptake at basal insulin
      concentrations. A secondary objective was to determine whether somatostatin
      affects the action of infused insulin. In part I of the experiment a primed
      continuous infusion [6,6-2H]glucose (45.2 micrograms/kg per min) was begun at
      time 0 and continued for 5 h. After 3 h of [6,6-2H]glucose infusion (basal
      period) a primed continuous infusion of insulin (0.001 i.u./kg per min) was
      administered for 2 h. Coincidental with the insulin infusion, normal glucose was
      also infused in order to maintain the plasma glucose concentration at
      euglycaemia. Part II of the experiment was the same as part I except that
      somatostatin was infused for 2 h (0.333 micrograms/kg per min) instead of
      insulin. In part III of the experiment both insulin and somatostatin were infused
      for the final 2 h. Plasma insulin levels were increased by insulin infusion (to
      0.1476 to 0.1290 i.u./l for parts I and III respectively) and were reduced by
      somatostatin infusion in part II (to 0.006 i.u./l) relative to the basal periods
      (mean 0.021 i.u./l). Glucose uptake during somatostatin infusion (2.50 mg/kg per
      min; part II) was 92.0% of that observed in the respective basal period (2.72
      mg/kg per min). Circulating insulin levels were much lower than the dose of
      insulin that causes a half maximal effect on glucose uptake (0.06-0.10 i.u./l for
      ruminants); consequently insulin-mediated glucose uptake was probably absent in
      part II. Secondly, glucose uptake following insulin only infusion (4.05 mg/kg per
      min) was significantly lower than that observed when insulin plus somatostatin
      was infused (4.69 mg/kg per min), indicating that somatostatin either directly or
      indirectly enhanced the action of insulin on glucose uptake.

PMID- 9275255
TI  - 15N enrichments of casein and plasma protein amino acids in cows ingesting 15N
      labelled ammonium sulphate.
AB  - The aim of this work was to determine by ion-exchange liquid chromatography and
      isotope ratio mass spectrometry the specific 15N enrichment of amino acids in
      casein and plasma proteins in cows receiving three successive daily oral doses
      (300, 150 and 150 g) of (15NH4)2SO4 (10 atom per cent isotopic enrichment) and to
      examine the 15N enrichments obtained with regard to nitrogen transport and
      metabolism in the lactating cow. To investigate the 15N distribution in amino
      acids in casein and in plasma proteins, samples of 15N-labelled casein and plasma
      proteins were extracted either from a pool of several milkings (36-96 h after
      starting to administer the tracer) or from pooled venous blood (removed on the
      fourth day after the start of administration) from the four lactating cows. 15N
      enrichments of the proteins studied, expressed as atoms percent excess, were
      0.2509 for casein and 0.0577 for plasma protein. Chromatographic fractionation of
      the amino acid mixture (protein hydrolysates) resulted in nine groups containing
      between one and four amino acids: Asp, Ser and Thr; Glu; Pro; Gly; Ala; Val and
      Met; Ileu and Leu; Tyr; Phe; His and Lys; and Arg. High 15N incorporation was
      demonstrated in all individual or groups of amino acids studied. In both
      proteins, Glu appeared to be the most enriched amino acid, Phe and Arg the least
      enriched. Most aliphatic molecules with a single amino group were highly
      enriched. The much lower (3.5-7.7-fold) enrichments in plasma protein compared
      with casein suggest considerable intracellular dilution at the site of liver
      protein synthesis. Finally, the amino acid separation methods are discussed and
      suggestions for improving them considered.

PMID- 9275256
TI  - Solution conformation of a peptide corresponding to bovine kappa-casein B
      residues 130-153 by circular dichroism spectroscopy and 1H-nuclear magnetic
      resonance spectroscopy.
AB  - The peptide Pro130-Thr-Ser-Thr-Pro-Thr-Ile-Glu-Ala-Val-Glu140- Ser-Thr-Val-Ala
      Thr-Leu-GLu-Ala-Ser-Pro150-Glu-Val-Ile, which corresponds to residues 130-150 of
      kappa-casein B, was synthesized and the conformation of the peptide in solution
      investigated by circular dichroism (CD) spectroscopy, structure prediction
      algorithms and 1H-nuclear magnetic resonance spectroscopy. In a solution
      containing the structure-enhancing solvent trifluoroethanol the CD spectrum was
      typical of a peptide in the alpha-helical conformation and nuclear magnetic
      resonance showed that the amino acids between Ile136 and Ser149 (kappa-casein
      numbering) were predominantly in the alpha-helical conformation but that Pro130
      to Thr135 and Pro150 to Ile153 were not. In addition, Thr133-Pro134 and Ser-149
      Pro150 were primarily in the trans conformation, the residues from Thr131 to
      Thr135 were in unordered structures and the residues from Glu151 to Ile153 were
      in an extended conformation. Residues Glu137 to Glu140 and Thr145 to Ala148 also
      displayed some 3(10)-helix character. When the peptide was dissolved in 10 mM
      cetyltrimethylammonium chloride solution at pH 6, the CD spectra indicated that
      the proportion of helical structure was comparable to that of the peptide in
      trifluoroethanol solution (400 ml/l), whereas when the peptide was dissolved in
      buffer alone in 10 mM-SDS solution, the CD spectra were consistent with a low
      helical content. Acidification of these solutions to pH 2.85 resulted in a slight
      increase in the helical content of the peptide in buffer and more markedly in
      buffer containing SDS. When the peptide was in 5 mM-CaCl2 solution at neutral pH,
      the CD spectrum indicated that some ordered structure was present. Taken together
      these results indicate that the ionizable residues Glu137, Glu140, Glu147 and
      Glu151 could be important in determining the stability of the putative helix. The
      structure predictions found that the sequence from Glu137 to Pro150 would be more
      likely to be in a helical than any other conformation in the intact bovine
      protein, but that pig, sheep and goat kappa-caseins did not give a prediction of
      a strongly helical region in this part of the molecule.

PMID- 9275257
TI  - Purification and characterization of aminopeptidase P from Lactococcus lactis
      subsp. cremoris.
AB  - Aminopeptidase P was purified 65.3-fold from the cytoplasm of Lactococcus lactis
      subsp. cremoris AM2 with a 5.8% yield. The purified enzyme was found to consist
      of one polypeptide chain with a relative molecular mass of 41,600. Metal
      chelating agents were found to be inhibitory and Mn2+ and Co2+ stimulated
      activity 7-fold and 6-fold respectively. The purified enzyme removed the N
      terminal amino acid from peptides only where proline (and in one case alanine)
      was present in the penultimate position. No hydrolysis was observed either with
      dipeptides even when proline was present in the C-terminal position or when
      either N-terminal proline or pyroglutamate was present preceding a proline
      residue in the penultimate position of longer peptides. On the basis of this
      substrate specificity either aminopeptidase P or post-proline dipeptidyl
      aminopeptidase are necessary along with a broad specificity aminopeptidase to
      effect complete hydrolysis of casein-derived peptides containing a single
      internally placed proline residue. However, both aminopeptidase P and post
      proline dipeptidyl aminopeptidase would be required together with a broad
      specificity aminopeptidase in order to completely hydrolyse casein-derived
      peptides that contain two internally placed consecutive proline residues. As
      bitter casein-derived peptides are likely to contain either single prolines or
      pairs of prolines, aminopeptidase P appears to be an important enzyme for
      debittering.

PMID- 9275258
TI  - Isolation and identification of further peptides in the diafiltration retentate
      of the water-soluble fraction of Cheddar cheese.
AB  - Several peptides were isolated from the diafiltration retentate, prepared using
      10 kDa membranes, of the water-soluble extract from a commercial mature Cheddar
      cheese and identified by amino acid sequencing and mass spectrometry. Most of the
      peptides were from the N-terminal half of the beta-casein, but peptides from
      alpha s1- and alpha s2-caseins were also identified; the extract also contained
      alpha-lactalbumin. Identified peptides showed the important role played by
      lactococcal cell envelope proteinases in the degradation of primary proteolytic
      products from alpha s1- and beta-caseins, produced by chymosin and plasmin
      respectively. Plasmin seemed to be involved in the hydrolysation of alpha s2
      casein. Several phosphopeptides were identified and the action of phosphatase on
      these peptides was evident.

PMID- 9275259
TI  - Effect of yogurt and bifidus yogurt fortified with skim milk powder, condensed
      whey and lactose-hydrolysed condensed whey on serum cholesterol and
      triacylglycerol levels in rats.
AB  - The possible hypocholesterolaemic properties of milk and fermented milk products
      have been investigated in groups of albino rats given a basal diet, basal diet
      plus cholesterol, and basal diet plus cholesterol together with whole milk or
      standard or bifidus yogurt. The yogurts were fortified with skim milk powder,
      condensed whey or lactose-hydrolysed condensed whey. After 30 d,
      triacylglycerols, total cholesterol, HDL-cholesterol and LDL-cholesterol were
      measured in serum. Whole milk and ordinary yogurt had no hypocholesterolaemic
      effect, but standard yogurt containing lactose-hydrolysed condensed whey and all
      bifidus yogurts lowered serum cholesterol. In general, yogurts changed HDL
      cholesterol little, but tended to raise triacylglycerols. There was marked
      lowering of LDL-cholesterol in rats given either type of yogurt fortified with
      whey proteins. This study has demonstrated in a rat model that bifidus yogurts
      and yogurts fortified with whey proteins can reduce total and LDL-cholesterol,
      and suggests that if they have the same effect in human subjects they have
      potential value in cholesterol-lowering diets.

PMID- 9275260
TI  - Preparative-scale fractionation of bovine, caprine and ovine whey proteins by bel
      permeation chromatography.

PMID- 9275261
TI  - Method for the measurement of lipase activity in milk.

PMID- 9275262
TI  - Mineral content of camel milk and colostrum.

PMID- 9275263
TI  - Laminitis in the dairy cow: a cell biological approach.

PMID- 9275264
TI  - Case-control studies of the efficacy of screening for cancer: can we earn them
      some respect.

PMID- 9275265
TI  - Screening for Huntington disease and certain other dominantly inherited
      disorders: a case for preimplantation genetic testing.

PMID- 9275267
TI  - Reliability of statistics on Down's syndrome notifications.
AB  - OBJECTIVES: To evaluate the completeness of notifications of Down's syndrome live
      births and terminations to the Office for National Statistics (ONS) using data
      from the National Down Syndrome Cytogenetic Register (NDSCR). To examine the
      agreement of observed birth prevalence of Down's syndrome with the expected birth
      prevalence derived from published maternal age specific rates. METHODS: The
      number of live births (adjusted to allow for the estimated underascertainment)
      and the number of terminations due to fetal Down's syndrome from NDSCR were
      compared with those figures reported to the ONS. Subsequently, using the NDSCR
      figures, the live birth prevalence of Down's syndrome that would have occurred in
      the absence of antenatal diagnosis and selective termination was calculated in
      England and Wales in the years 1990-1993. These figures were compared with those
      derived by applying published age specific prevalences to the maternal age
      distribution in England and Wales. RESULTS: It is estimated that only 48% and 46%
      respectively of Down's syndrome live births and terminations of pregnancy were
      notified to ONS between 1990 and 1993. The annual expected birth prevalences of
      Down's syndrome obtained by applying maternal age specific prevalences to the
      maternal age distribution were in close agreement with observed rates from NDSCR.
      CONCLUSIONS: There is considerable underreporting of Down's syndrome births and
      terminations to ONS. The NDSCR data are more complete and therefore the effects
      of screening should be monitored using data from this source, or using estimates
      derived from the age specific rates of Down's syndrome.

PMID- 9275266
TI  - Screening for fragile X syndrome: information needs for health planners.

PMID- 9275268
TI  - Use of two view mammography compared with one view in the detection of small
      invasive cancers: further results from the National Health Service breast
      screening programme.
AB  - OBJECTIVE: To examine further the effect of using two view mammography in
      comparison with one view mammography in the detection of small (< 15 mm) invasive
      cancers for programmes in the National Health Service breast screening programme
      (NHSBSP). The study is in two parts: first the effect on the small invasive
      cancer detection rate for programmes that changed from using one view to two
      views for first (prevalent) screens, and secondly the effect on the small
      invasive cancer detection rate for programmes that used two views for subsequent
      (incident) screens compared with programmes that used one view. SETTING:
      Screening programme data from the NHSBSP. METHODS: Data were collated from all
      screening programmes in the United Kingdom on standard "Korner" returns (KC62
      forms) for the screening years 1 April 1994 to 31 March 1995 and 1 April 1995 to
      31 March 1996. The comparison between one and two view mammography was made using
      indirectly age standardised invasive cancer detection rates. RESULTS: For
      prevalent (first) screens, programmes changing from one view mammography in
      1994/95 to two views in 1995/96 reported a 45% (95% confidence interval (CI) 25%
      to 68%) increase in the detection of invasive cancers of < 15 mm. In comparison,
      programmes that were already using two views in 1994/95 showed no change in
      1995/96. For incident (subsequent) screens the small number of programmes that
      have opted to use two views reported 25% (95% CI 1% to 55%) more invasive cancers
      of < 15mm than programmes using one view in 1995/96, and 42% (95% CI 11% to 81%)
      more in 1994/95. CONCLUSIONS--These results confirm the benefit of using two view
      mammography in the detection of small invasive cancers, and provide evidence that
      this effect is seen in subsequent screens as well as the first screen.

PMID- 9275269
TI  - Randomised trial of prostate cancer screening in The Netherlands: assessment of
      acceptance and motives for attendance.
AB  - OBJECTIVES: To assess motives for attending a randomised population based
      prostate cancer screening trial, and to assess acceptance of screening and
      invitation procedures. METHODS: First pilot of the European Randomised Study of
      Screening for Prostate Cancer (ERSPC; 1992/1993). Men aged 55-75 years, randomly
      selected from the population register of four city districts of Rotterdam, were
      invited by a single invitation for screening. Screening consisted of prostate
      specific antigen prescreening followed by either (1) digital rectal examination,
      transrectal ultrasound, and, on indication, biopsy, or (2) no additional
      screening. After screening, or in the case of non-attendance, a questionnaire was
      sent to a random sample of 600 attenders and 400 non-attenders, with a reminder
      after three weeks. OUTCOME MEASURES: In both attenders and non-attenders:
      knowledge of prostate cancer, attitudes towards screening, motives for attending,
      procedural aspects and sociodemographic characteristics. In attenders, acceptance
      of screening procedures. RESULTS: The response rate for the questionnaire was
      76%: 94% in attenders and 42% in non-attenders. The main reasons for attending
      were expected personal benefit (76%) and scientific value (39%), and those for
      not attending were absence of urological complaints (41%) and anticipated pain or
      discomfort (24%). Uptake of screening was 32%, which increased to a sustained 42%
      in following years. Attenders, compared with non-attenders, were significantly
      younger, more often married, better educated, and had higher perceived health
      status, more knowledge about prostate cancer, and a more positive attitude
      towards screening. Information materials and invitation procedures were well
      accepted (high report marks and satisfaction, and 95% would attend for
      rescreening). A single prostate specific antigen determination was liked less
      than a combination of all three screening modalities. CONCLUSIONS: (1) The main
      reasons for attending are personal benefit and science, and those for not
      attending were absence of urological complaints and anticipated pain or
      discomfort; (2) knowledge, attitudes, and motives for attending are comparable
      with other screening programmes; hence, for population based prostate cancer
      screening, known health promotional aspects should be carefully considered; (3)
      prostate specific antigen, digital rectal examination and transrectal ultrasound
      are acceptable to attenders.

PMID- 9275270
TI  - Cervical screening of Arabic-speaking women in Australian general practice.
AB  - OBJECTIVE: To determine recency and predictors of cervical screening among Arabic
      speaking women in Sydney, Australia. METHOD: A consecutive sample of Arabic
      speaking women, attending 20 Arabic-speaking general practitioners, was asked to
      complete a self administered health risk questionnaire available in Arabic or
      English which included three questions about cervical screening knowledge and
      behaviour. RESULTS: Of 756 eligible women, 526 (70%) returned completed
      questionnaires. Of these, 69 (13%) did not know what a cervical smear was.
      Sixteen per cent of overseas-born compared with 2% of Australian-born women at
      risk had not heard of a cervical smear. Women were defined as being at risk of
      cervical cancer if they had both been married and not had a hysterectomy. Of 318
      women at risk for cervical cancer who knew what a cervical smear was, 66% had had
      a smear in the last two years, a further 7% were attending for one that day while
      11% had not had a smear for at least two years, 9% had never had one and 7% did
      not answer/could not remember. Religion, age, and residence in Australia for more
      than 10 years were significant and independent predictors of screening after
      adjustment for other variables in simultaneous logistic regression model (P =
      0.002, P = 0.002, and P = 0.040 respectively). Muslim women and older women were
      more likely to be underscreened, and women with more than 10 years' residence in
      Australia were more likely to have been screened in the last two years.
      Acculturation, smoking status, health status, duration of relationship with
      participating doctor, and chronic disease were not significant predictors of a
      recent smear. CONCLUSION: As only 73% of women at risk had been screened in the
      last two years, including women attending on the day and 9% had never been
      screened, Arabic-speaking women should be a priority for public campaigns,
      particularly Muslim and older women. Studies to evaluate the effectiveness and
      acceptability of reminders by ethnic general practitioners are recommended.

PMID- 9275272
TI  - Site-specific endonuclease AbaI from Azospirillum brasilense UQ 1796 is an
      isoschizomer of endonuclease BclI.
AB  - The site-specific endonuclease AbaI was isolated and purified to functional
      purity from the soil nitrogen-fixing bacterium Azospirillum brasilense UQ 1796.
      Purification included successive chromatography on columns with phosphocellulose,
      heparin-Sepharose, and hydroxyapatite. The purified enzyme recognizes the
      palindromic DNA sequence 5'-T decreases ATCA-3' and cleaves it as shown by the
      arrow. The isolated enzyme belongs to class II restriction endonuclease and is an
      isoschizomer of endonuclease BclI. The enzyme of AbaI is active at 26-56 degrees
      C. The optimal temperature is 48 degrees C and the optimal buffer is LRB.

PMID- 9275273
TI  - Sex differences in biotransformation of the xenobiotic p-nitroanisole in isolated
      rat hepatocyte under the influence of phenobarbital.
AB  - Different sensitivity of the xenobiotic biotransformation system to phenobarbital
      treatment in female and male rat hepatocytes is shown. Hepatocytes isolated from
      females had less cytochrome P-450 content and metabolized the xenobiotic p
      nitroanisole (p-NA) more slowly than hepatocytes from males. Phenobarbital
      treatment increased the cytochrome P-450 amount and the p-nitrophenol (p-NPh)
      formation rate in hepatocytes from female and male rats to the same extent.
      However, in control and female induced cells the main form of p-NPh was so
      conjugates, while induction of male rats reactions of conjugation were depressed
      and free p-NPh accumulated. The sex differences in the response of xenobiotic
      biotransformation system to an inducing treatment should be taken into account
      into transplantation and prescription of drug treatment courses.

PMID- 9275274
TI  - The immobilized matrix buffer controls the rate of mitochondrial respiration in
      state 3P according to chance.
AB  - Preparations of coupled mitochondria were labeled with fluorescein isothiocyanate
      (FITC). Comparison of characteristics of FITC bound to mitochondria versus
      azolectin liposomes indicates that a significant part of the probe is bound to
      mitochondrial proteins including proteins of the matrix side of the inner
      membrane. The experiments with the probe indicate that mitochondrial proteins
      resemble typical polyelectrolytes with constant of dissociation close to 10(
      7).H+ and K+ compete for binding to mitochondrial proteins at neutral pH. The
      slow deprotonation of matrix proteins is observed during equilibration of matrix
      protons with medium protons. This process is not restricted to the transmembrane
      proton transfer. The data are explained by the theory of immobilized buffer.
      Under certain conditions the extent of dissociation of the matrix immobilized
      buffer correlates with the rate of mitochondrial respiration in state 3P
      according to chance.

PMID- 9275276
TI  - Comparative kinetic characterization of catalases from Candida boidinii yeast and
      bovine liver.
AB  - Catalase with molecular weight 230 +/- kD was isolated and purified from
      methylotrophic yeasts Candida boidinii by ion-exchange chromatography. The
      kinetic characteristics of yeast and bovine liver catalases were compared in the
      reaction of H2O2 decomposition using a wide range of H2O2 concentrations (up to
      0.12 M) and PH (2-10). First order rates constants (k, sec-1) were determined for
      both enzymes from semi-logarithmic anamorphoses of kinetic curves of H2O2
      utilization. Anamorphoses of complete kinetic curves as a function of
      1/ln([H2O2]0/[H2O2]t) versus 1/t were used for calculation of the effective rate
      constants of catalase inactivation during the reaction (k(in), sec-1) and the
      rate constants of interaction of catalase complex I with the second molecule of
      H2O2 (k2, M-1.sec-1). The effects of initial catalase concentrations, H2O2, and
      pH on k, k2, and k(in) were similar for both enzymes. Catalytic constant, k2, and
      the efficacy expressed as a ratio kcat/Km were 1.87-, 1.45-, and 1.3-fold,
      respectively, higher for bovine catalase than that of yeast catalase. Operational
      stability of yeast catalase is 3.5-fold higher than the stability of bovine
      catalase and much higher during cyclic decomposition of 50 mM H2O2. Enhanced
      operational stability and inexpensive source of its preparation open prospects
      for practical applications of yeast catalase for co-immobilization with
      superoxide dismutase on non-toxic carriers.

PMID- 9275275
TI  - Relationship between state of a thermosensitive matrix and the activity of urease
      immobilized in it.
AB  - The effect of temperature on kinetic and equilibrium parameters of urea
      hydrolysis catalyzed with urease immobilized into a thermosensitive poly-N
      isopropylacrylamide gel was studied. The temperature behavior of the gel-urease
      system is different from similar systems. After a decrease in the enzyme activity
      above the critical temperature, the maximal rate of the enzymatic reaction and
      gel swelling ratio begin to increase. Urea hydrolysis catalyzed with immobilized
      urease and shrinking-swelling of the thermosensitive urease-containing gel depend
      on each other. Under collapse, gel swelling increases due to the enzymatic
      reaction. The rate of the enzymatic reaction no longer follows Michaelis-Menten
      kinetics, and the dependence of the reaction rate on substrate concentration
      becomes more complicated.

PMID- 9275277
TI  - A secretory protein involved in the antagonistic interactions between
      methanotrophic bacteria.
AB  - Antagonistic interactions in mixed culture of methanotrophic bacteria
      Methylomonas methanica 12 and Methylocystis minimus 33 were investigated. The
      inhibitory action of Mcs. minimus exometabolites against Mm. methanica grown in
      liquid medium was found to be specific. Ultrafiltration established that the
      molecular weight of the substance having inhibitory activity lies within the
      range 2-10 kD. The activity is protease sensitive and relatively stable to
      heating. Electrophoretic analysis showed that a protein with molecular weight of
      approximately 8 kD prevailed in Mcs. minimus culture liquid. When Mm. methanica
      cells were incubated in culture liquid of Mcs. minimus, the sorption of the 8 kD
      protein by target cells was observed. This suggests that the inhibitory effect
      may be associated with the 8 kD protein which has properties similar to known
      bacteriocins.

PMID- 9275278
TI  - Initiation of radicals in biochemical systems: ferritin-hydroperoxides-aromatic
      amines.
AB  - The rates of initiation of free radicals were determined in systems containing
      horse spleen ferritin, H2O2, tert-butyl hydroperoxide (TBHP) or cumene
      hydroperoxide (CHP) in acetate buffer (pH 4.2) or phosphate buffer (pH 6.0) with
      10-15% dimethylformamide (DMF). Benzidine (BD), benzidine sulfate (BDS), o
      tolidine (TL), 3,3',5,5'-tetramethylbenzidine (TMB), and o-phenylenediamine (PDA)
      were used as acceptors. In the systems ferritin-H2O2 oxidation of amine acceptor
      follows Michaelis-Menten kinetics. For all aromatic amines kcat, Km, and their
      ratios were determined. Peroxidase efficiency of ferritin in the TMB oxidation by
      hydrogen peroxide (kcat/km) is characterized by a value 2.82.10(3) M-1.sec-1
      comparable with ferroxidase efficiency of apoferritin in the oxidation of Fe2+ by
      oxygen. Reactivity of aromatic amines in the system ferritin-H2O2 is similar to
      the reactivity registered in their peroxides oxidation and is maximal for TMB and
      PDA. Bimolecular rate constants of TMB and PDA oxidation in the reaction with
      H2O2, TBHP, and CHP were compared in acetate buffer (pH 4.2 using 0.5 microM
      ferritin and 5 mM concentration of each substrate. On the oxidation of both
      amines activity of oxidants decreased in the following order: H2O2 > TBHP > CHP.
      A scheme of radical initiation in the systems ferritin-ROOH (H2O2)-amines and the
      influence of radical acceptors apoferritin and organic co-solvent on the rate of
      reactions are discussed.

PMID- 9275279
TI  - Expression of functionally active cytochrome b5 in Escherichia coli: isolation,
      purification, and use of the immobilized recombinant heme protein for affinity
      chromatography of electron-transfer proteins.
AB  - Cytochrome b5 is an integral membrane protein which is localized in endoplasmic
      reticulum membranes. In this paper we present the results on expression in E.
      coli, purification, and characterization of recombinant rat cytochrome b5. The
      full-length cDNA for rat liver microsomal cytochrome b5 has been modified using
      polymerase chain reaction (PCR) to introduce corresponding restriction sites as
      well as to insert silent mutations in the N-terminal sequence to increase the
      content of A and T nucleotides that prevents formation of elements of secondary
      structure of the mRNA transcripts and facilitates high expression. The expression
      plasmid was constructed by cloning of amplified cDNA to pCWori+ plasmid and used
      for transformation of E. coli DH5 alpha. The optimization of recombinant
      cytochrome b5 expression procedure induces expression level up to 3000 nmoles per
      liter of growth medium; this confers in the cells a deep pink color. The most
      interesting fact is that cytochrome b5 is expressed in this system in the reduced
      state. Recombinant cytochrome b5 was purified from solubilized cell membranes by
      a combination of ion-exchange chromatography and gel filtration. During
      purification, part of the cytochrome b5 is subjected to limited proteolysis with
      formation of truncated form. Sequencing of the N-terminal part of the recombinant
      cytochrome b5 indicates that it coincides with the sequence of rat cytochrome b5.
      Recombinant cytochrome b5 was found to have physicochemical, catalytic, and
      immunochemical properties to that of the native protein and was used as an
      efficient affinity matrix for purification of the various electron-transfer
      proteins.

PMID- 9275281
TI  - Tryptophan synthase from Agrobacterium tumefaciens 8628: isolation and
      properties.
AB  - Tryptophan synthase was isolated from a highly virulent strain of Agrobacterium
      tumefaciens 8628 (octopine type). Separation of tryptophan synthase from
      thermolabile protease was accomplished using fractionation with polyethylene
      glycol-6000 followed by ion-exchange chromatography with a pH gradient. Molecular
      weights of alpha- and beta-subunits are 33 and 51 kD, respectively. The
      tryptophan synthase is stable at 60 degrees C because of heat-tolerance beta
      subunits. After heating the activity of tryptophan synthase increased up to 20
      times while temperature-labile proteases lost their activities. Reaction with
      antibodies showed the presence of four protein bands, one of which was coeluted
      with nucleic acids during ion-exchange chromatography. It is suggested that the
      basic tryptophan synthase is encoded by trp genes in a plasmid and its role is to
      provide the precursor with the prokaryotic pathway of indole-3-acetic acid
      biosynthesis, which determines the virulence of A. tumefaciens. There is perhaps
      a cooperation between iaaM, iaaH, and trp genes in the plasmid during plant cell
      transformation.

PMID- 9275280
TI  - Determination of constants of substrate primary binding with baker's yeast
      transketolase by kinetic modelling.
AB  - A kinetic model of bisubstrate reaction catalyzed by baker's yeast transketolase
      is proposed. The model considers individual stages of substrates reversible
      primary binding. The model corresponds to the observed kinetics of product
      accumulation within a wide range of initial substrate concentrations. Kinetic
      parameters for the best simulation of the experimental data are defined. The
      equilibrium constants of the primary binding of both the initial and produced
      ketose and also the initial aldose were unequivocally determined by varying the
      initial substrate concentrations. The dissociation constants of the primary
      enzyme-substrate complex for the initial ketose (xylulose 5-phosphate) and the
      reaction product (sedoheptulose 7-phosphate) were found to differ by more than by
      two orders of magnitude. The result is discussed in the context of the hypothesis
      of flip-flop functioning of the transketolase active sites.

PMID- 9275282
TI  - Epitope mapping of horseradish peroxidase (isoenzyme C).
AB  - Peptide scanning (PEPSCAN) was used to determine linear antigenic determinants of
      horseradish peroxidase isoenzyme C (HRPC). For this purpose, we synthesized 303
      overlapping hexapeptide fragments (with a step of one amino acid residue) of the
      protein primary structure and studied their interactions with anti-HRPC
      polyclonal antisera by ELISA. Experiments with various titers of antisera allowed
      us to determine linear antigenic determinants of HRPC; several such determinants
      were spatially located in regular elements of the secondary structure (alpha
      helices) found both inside and outside the protein globule. A fraction of
      epitopes were located in loops and folds of the HRPC peptide chain with irregular
      shapes. These epitopes contained several functionally important residues: Arg 38,
      which is part of the active site of the enzyme, as well as Phe 142 and Phe 143,
      which form a channel allowing aromatic substrates to reach the active site. Amino
      acid residues that form calcium-binding sites or occur in the vicinity of
      disulfide bonds are not involved in these epitopes.

PMID- 9275283
TI  - The influence of some compounds commonly used in biochemical studies of
      mitochondria on the activity of monoamine oxidases.
AB  - It was previously described that low concentrations of sodium azide monoamine
      oxidase (MAO) B assayed by spectrophotometric measurement of benzaldehyde or by
      hydrogen peroxide accumulation. We failed to confirm this effect using
      radiometric determination of MAO activity. Tris or dinitrophenol inhibit MAO. The
      data suggest that some "regulatory effects" depend on the assay of MAO activity.

PMID- 9275284
TI  - The beta CK2tes gene encodes the tissue-specific regulatory subunit of casein
      kinase 2 in Drosophila melanogaster.
AB  - The beta CK2tes gene encodes a new variant of the tissue-specific regulatory beta
      subunit of casein kinase 2 (CK2). The beta CK2tes open reading frame comprises
      nucleotide stretches encoding for the conservative polypeptide motifs
      characteristic for the CK2 beta-subunit including the Glu/Asp rich region
      responsible for regulation of CK2, C-terminal fragment responsible for binding to
      the catalytic alpha-subunit, and "zinc finger" motif. Unlike conserved sequences
      of CK2 beta-subunits in other organisms the beta CK2tes polypeptide has no
      autophosphorylation site or other putative phosphorylation sites. beta CK2tes is
      expressed only in testes, whereas beta CK2 expression is maximal at embryonic
      stages and is detected also in larvae. We suggest that beta CK2tes determines
      substrate specificity of CK2 and/or CK2 activity during spermatogenesis in
      Drosophila.

PMID- 9275285
TI  - Structure of the acid-labile galactosyl phosphate-containing O-antigen of the
      bacterium Proteus vulgaris OX19 (serogroup O1) used in the Weil-Felix test.
AB  - The structure of the O-specific polysaccharide chain of Proteus vulgaris OX19
      lipopolysaccharide which determines the O1 specificity of Proteus and is used in
      the Weil-Felix test for diagnostics of rickettsiosis was established. On the
      basis of 1H- and 13 C-NMR spectroscopy, including two-dimensional correlation
      spectroscopy (COSY), H-detected 1H, 13C heteronuclear multiple-quantum coherence
      (HMQC), and rotating-frame nuclear Overhauser effect spectroscopy (ROESY), it was
      found that the polysaccharide consists of branched pentasaccharide repeating
      units containing D-galactose, 2-acetamido-2-deoxy-D-glucose, 2-acetamido-2-deoxy
      D-galactose, and 2-acetamido-2,6-dideoxy-D-glucose (QuiNAc, two residues), which
      are connected to each other via a phosphate group (P): [formula: see text]. The
      polysaccharide is acid-labile, the glycosyl phosphate linkage being cleaved at pH
      4.5 (70 degrees C) to give a phosphorylated pentasaccharide with a galactose
      residue at the reducing end. Structural analysis of the oligosaccharide and a
      product of its dephosphorylation with 48% hydrofluoric acid using 1H- and 13C-NMR
      spectroscopy and electrospray ionization mass spectrometry confirmed the
      structure of the polysaccharide.

PMID- 9275286
TI  - Preparation and characterization of monoclonal antibodies to foot-and-mouth
      disease virus type Asia-1.
AB  - Eight clones of hybrid cells secreting monoclonal antibodies to foot-and-mouth
      disease virus type Asia-1 were prepared; three of them neutralized viral
      infection. The specificity of THE monoclonal antibodies was analyzed by various
      immunoenzyme assays using 146S viral particles, trypsin-treated 146S particles,
      12S particles, and certain viral polypeptides. The epitopes unique for virus type
      Asia-1 and conservative among several types were detected on the surface of viral
      particles. Epitopes on the surface of viral particle were mapped.

PMID- 9275287
TI  - RNA-hydrolyzing antibodies from peripheral blood of patients with lupus
      erythematosus.
AB  - Experiments and hydrolysis of substrates with known spatial structures (such as
      yeast tRNAPhe, as well as normal and mutant tRNALys from human mitochondria
      produced by transcription of the appropriate DNA species, that is, RNA genes)
      were performed to study the ribonuclease activity of antibodies isolated from
      blood sera of patients with systemic lupus erythematosus (SLE). The antibody
      preparations contained two types of ribonuclease activities: the first
      corresponded to the specificity of ribonuclease A and was found during hydrolysis
      at low salt concentrations, whereas the second was stimulated by Mg2+ and
      displayed unique specificity toward double-stranded regions of the substrate. The
      possible use of the antibody preparations as tools for structural studies of
      conformational differences between RNA molecules was examined. In experiments
      with unmodified and mutant tRNALys species differing in one base found in the T
      loop, we found that hydrolysis with SLE antibodies can detect small local
      structural changes in RNA under physiological conditions.

PMID- 9275288
TI  - Effects of penetrating and non-penetrating oxidants on Escherichia coli.
AB  - Treatment of Escherichia coli K-12 cells aerobically grown in M9 glucose salt
      medium (H2O2) and non-penetrating (ferricyanide) oxidants resulted in similar
      inhibition of growth and decrease in intracellular K+ pool by 15%. Only H2O2
      inhibited growth of auxotrophic strains grown in M9 medium supplemented with
      protein hydrolysate. Ferricyanide reduction was associated with decrease in low
      molecular-weight thiols, whereas the treatment of cells with H2O2 increased their
      level. Pretreatment of cells with ferricyanide enhanced the H2O2-induced
      expression of katG gene encoding for catalase HPI; this gene is a member of the
      gene family controlled by the oxyR gene. Pretreatment with ferricyanide inhibited
      H2O2-induced expression of the sfiA gene which is the member of the gene family
      controlled by the recA and lexA genes. Glutathione is the major low-molecular
      weight thiol in E. coli, and it can play different roles in cellular responses to
      H2O2 and ferricyanide.

PMID- 9275289
TI  - Effect of cysteinesulfinate on fatty acid-dependent uncoupling: modulation of
      recoupling by substrates of the aspartate/glutamate antiporter and diethyl
      pyrocarbonate.
AB  - The action of cysteinesulfinate, the substrate of the aspartate/glutamate
      antiporter on the palmitate-induced uncoupling in rat liver mitochondria and the
      recoupling effect of glutamate, aspartate, and diethyl pyrocarbonate was studied.
      In the presence of palmitate and an inhibitor of the ADP/ATP-antiporter
      carboxyatractylate, cysteinesulfinate exerted a relatively week recoupling
      effect. However, it significantly decreased the recoupling action of glutamate,
      aspartate, and diethyl pyrocarbonate. In the presence of cysteinesulfinate, these
      compounds caused recoupling at higher concentrations. The data show that the
      recoupling action of glutamate, aspartate, and diethyl pyrocarbonate is due to
      their interaction with the aspartate/glutamate antiporter. The data also confirm
      the suggestion that this anion carrier is involved in the uncoupling action of
      fatty acids.

PMID- 9275291
TI  - Structure of the O-specific polysaccharide of the bacterium Proteus mirabilis O13
      containing a novel component: an amide of D-galacturonic acid with N(epsilon)-(1
      carboxyethyl)lysine.
AB  - An acidic O-specific polysaccharide was obtained by mild degradation of the
      lipopolysaccharide of the bacterium Proteus mirabilis O13 and found to contain D
      galactose, 2-acetamido-2-deoxy-D-glucose, and N(epsilon)-(1-carboxyethyl)
      N(alpha)-(D-galacturonoyl)lysine. On the basis of full acid hydrolysis and 1H-
      and 13C-NMR spectroscopy, including two-dimensional correlation spectroscopy
      (COSY), H-detected heteronuclear 1H, 13C multi-quantum coherence (HMQC), and
      rotating-frame nuclear Overhauser effect spectroscopy (ROESY), the following
      structure of the branched trisaccharide repeating unit of the polysaccharide was
      established [structure: see text]

PMID- 9275292
TI  - Molecular mechanisms of immunomodulating effect of chorionic gonadotropin on T-
      and B-lymphocytes of intact spleen.
AB  - Chorionic gonadotropin (CG) was injected into a short-term macroculture of
      fractionated splenocytes of female since F1(CBA x C57BL/6) in concentrations of
      10 or 50 IU/ml. The regulatory effects of CG were assessed in a syngeneic
      transfer system by the number of antibody-producing cells (APC) of the recipients
      CG at a dose of 10 IU/ml selectively activated the intact B-lymphocytes and
      failed to affect the functional activity of T-cells. The effects of low hormone
      doses were associated with the inositide system of secondary messengers and a
      decrease in the level of cAMP during the influence of the hormone. The dose of 50
      IU/ml also suppressed cAMP in B-lymphocytes but the number of APC did not change
      and failed to depend on the inhibitor of inositol-1-monophosphatase. The high
      dose of CG significantly increased the level of cAMP in the T-lymphocytes, and
      this was associated with a significant suppression of the functional activity of
      these cells. Different effects of the high and low hormone doses on different
      populations of the spleen immunocompetent cells found in vitro were also
      confirmed in vivo on ovariectomized donor females.

PMID- 9275290
TI  - Structure of the O-specific polysaccharide of the bacterium Providencia
      alcalifaciens O23 containing a novel component: an amide of D-glucuronic acid
      with N(epsilon)-(1-carboxyethyl)lysine.
AB  - An acidic O-specific polysaccharide was obtained by mild acid degradation of the
      lipopolysaccharide of the bacterium Providencia alcalifaciens O23 and found to
      contain D-glucose, D-galactose, 2-acetamido-2-deoxy-D-galactose, and N epsilon-(1
      carboxyethyl)-N alpha-(D-glucuronoyl)lysine. On the basis of full and partial
      acid hydrolyses, selective solvolysis with anhydrous hydrogen fluoride, and 1H-
      and 13C-NMR spectroscopy, including two-dimensional correlation spectroscopy
      (COSY), H-detected heteronuclear 1H, 13C multi-quantum coherence (HMQC), and
      rotating-frame nuclear Overhauser effect spectroscopy (ROESY), the following
      structure of the liner tetrasaccharide repeating unit of the polysaccharide was
      established [structure: see text]

PMID- 9275293
TI  - Calcium-binding characteristics and conformational changes in metastasin, a
      member of S-100 protein family.
AB  - Investigation of Ca(2+)-binding characteristics of metastasin (Mts-1) by
      competition with Fluo-3 revealed two types of Ca(2+)-binding sites in Mts-1 with
      the geometric mean of their dissociation constant (Kd) value of 2.6 microM for
      the two EF-sites. The Hill coefficient (nH) is 0.98. A substantial increase in
      the affinity of Mts-1 for Ca2+ and strong cooperative character of binding (kd =
      0.2 microM, nH = 1.91) is observed in the presence of the target protein p37
      isolated from mouse adenocarcinoma cell lines CSML-100 and CSML-0. Two different
      hydrophobic sites of binding with the fluorescent probe 2-(p-toludino)naphthalene
      6-sulfonate (TNS) per Mts-1 molecule have been determined. The exposure of the
      hydrophobic binding sites of the first type are shown to be Ca(2+)-dependent and
      the hydrophobic binding sites of the second type are exposed independently of
      Ca2+ concentration. A decrease in the number of Ca(2+)-dependent hydrophobic
      centers in the presence of p37 protein was detected by measurements of TNS
      fluorescence.

PMID- 9275294
TI  - RNA-binding properties of an unusual ribosomal protein TL5 from Thermus
      thermophilus.
AB  - The gene encoding the 5S rRNA-binding ribosomal protein TL5 from Thermus
      thermophilus, an extremely thermophilic species, was expressed in E. coli. A
      method for isolation of TL5 from the overproducing strain was developed. Samples
      of TL5 protein isolated from ribosomes and the overproducing strain displayed
      identical RNA-binding properties. Circular dichroic spectroscopy was used to
      calculate the secondary structure of the protein. TL5 was shown to form a stable
      complex with the 3'-terminal fragment of 5S rRNA, which is similar to the
      fragment of E. coli RNA that binds to L25 protein. The data suggest that TL5 from
      T. thermophilus and L25 from E. coli bind to similar sites on the 5S rRNA
      molecule.

PMID- 9275295
TI  - Ganglioside shedding and changes in ceramide biosynthesis in human ovarian
      tumors.
AB  - The contents and composition of ceramides and gangliosides were measured in human
      ovarian tumors (benign and malignant) and sera of tumor patients. In tumors
      (especially malignant) the content of ceramides is decreased compared to that in
      normal tissue, and the malignant tumor ceramides contain significant amounts of
      sphinganine which is absent in the ceramides of normal tissue, suggesting an
      alteration in ceramide biosynthesis. The content of gangliosides in tumors is
      also decreased. The major gangliosides of normal and tumor ovarian tissues are
      GM3 (sialocsyllactosyl ceramide) and GD3 (disialosyllactosyl ceramide). In
      tumors, the GD3 content is significantly decreased. The ceramide/ganglioside
      molar ratio in tumors is shifted toward gangliosides. In sera of tumor patients,
      ceramide content does not change, ganglioside content (especially that of GD3)
      increases compared to that in sera of healthy subjects due to ganglioside
      shedding from the surface of tumor cells, and the ceramide/ganglioside molar
      ratio decreases. These changes may stimulate tumor growth because of the opposite
      effects of ceramides and gangliosides: ceramides suppress tumor growth and
      gangliosides suppress antitumor activity.

PMID- 9275296
TI  - A hybrid mutant form of Escherichia coli inorganic pyrophosphatase.
AB  - The inorganic pyrophosphatase of Escherichia coli is a tightly hexamer of
      identical subunits. Upon interaction of its two mutant forms in which the trimer
      trimer contacts were weakened because of E20D and H136Q substitutions, a hybrid
      hexameric E20D/H136Q-PPase is formed. The catalytic activity of its constituent
      H136Q trimer is same of its hexamer, whereas metal-binding affinity is
      significantly decreased. These results point to an interdependence of two trimers
      in catalysis by hexameric pyrophosphatase.

PMID- 9275297
TI  - Effect of new peptide inhibitors on the ratio of angiotensin I-converting and
      kinin-degrading activities of dipeptidyl carboxypeptidase (angiotensin-converting
      enzyme).
AB  - The effect of N(alpha)-carboxyalkylated dipeptides on angiotensin-converting and
      kinin-degrading activity of angiotensin-converting enzyme (ACE, dipeptidyl
      carboxypeptidase) was studied. These inhibitors selectively affected ACE-induced
      hydrolysis of angiotensin I-like and bradykinin-like (hippuryl-His-Leu and
      hippuryl-Phe-Arg, respectively) substrates in microsomal fractions of rat lungs
      and kidneys and rat blood serum. The inhibition constants of both types of
      activity were determined for these enzyme preparations and also for ACE from
      porcine seminal fluid and highly purified ACE from porcine lung. In all cases
      high inhibition selectivity of angiotensin-generating and kininase activities of
      ACE was found.

PMID- 9275299
TI  - Prostaglandin H synthase of mouse macrophages: inhibiting and activating action
      of ibuprofen.
AB  - The effect of low (10(-10)-10(-14 M) ibuprofen concentrations on the release of
      labeled arachidonic acid metabolites by mouse peritoneal macrophages containing a
      constitutive isoform of prostaglandin H synthase was investigated. It was found
      that during the activation the cells metabolized AA through the cyclooxygenase
      pathway, synthesizing PGE2 (110 +/- 10 ng per 10(6) cells), PGF(2 alpha) (120 +/-
      15 ng per 10(6) cells), and TxB2 (48 +/- 5 ng per 10(6) cells). Incubation of the
      macrophages with 10(-12) M ibuprofen leads to a sharp increase of PGf2 and PGF(2
      alpha) synthesis (315 +/- 84 and 320 +/- 20 ng per 10(6) cells, respectively). A
      microsomal preparation of macrophage PGH-synthase was compared with PGH-synthase
      of ram seminal vesicles and analogy of their properties was shown (Km = 5.3.10(
      5) M, IC50, ibuprofen = 15 microM). Some particularities of the PGH-synthase
      consecutive isoform (PGH-synthase-1) cellular regulation are discussed.

PMID- 9275298
TI  - Composition and structural and functional properties of discoidal and spherical
      phospholipid-apoE3 complexes.
AB  - To model the common structural unit in the system of reverse cholesterol
      transport, we studied the composition, structure, and physicochemical properties
      of complexes generated between dipalmitoylphosphatidylcholine (DPPC) or
      palmitoyllinoleoylphosphatidylcholine (PLPC) and apoE3 in the absence and in the
      presence of cholesterol (Chol); the data were compared with similar experiments
      using apoA-I, the major proteins of high-density lipoproteins. The conformation
      and organization of lipid-binding domains of apoE3 within the complexes were
      calculated by computer modeling. The transition temperatures of DPPC within
      discoidal complexes with mean diameters of 116 A (GGE) or 148 A (EM) were higher
      for complexes versus liposomes both in the absence and in the presence of Chol.
      Association of apoE3 with DPPC resulted in a more structured state of the
      apolipoprotein molecule versus the soluble apolipoprotein; this state was
      characterized by parallel orientation of alpha-helixes of apoE3 and DPPC acyl
      chains. Substrate efficiency of the apoE3-PLPC-Chol complexes in the lecithin
      cholesterol acyltransferase (LCAT) reaction expressed as Vmax/Km was 0.5 mole
      cholesteryl esters/h per 1 microM. The transformation of discoidal apoE3-DPPC
      Chol complexes into spherical particles was induced by LCAT and accumulation of
      cholesteryl esters was approximately 62% of the total cholesterol. Parallel
      orientation of phospholipid acyl chains with helical segments disappeared in
      these particles. Discoidal apoE3-DPPC complexes incorporated unesterified
      cholesterol released from Chol-loaded J774 macrophages. The data support the
      concept that association of apoE3 and apoA-I with phospholipids is qualitatively
      similar due to similar orientation of helical repeats in the C-terminal domains
      of apoE3 and apoA-I.

PMID- 9275301
TI  - Involvement of metallothioneins in regulation of macrophage activity after
      combined radiation and thermal injury.
AB  - The levels of reduced metallothioneins (MT) in peritoneal macrophages and liver
      of mice subjected to combined radiation and chemical injury displayed opposite
      changes: the macrophage level of MT decreased and the liver MT increased.
      Simultaneously, there was an increase in luminol- and lucigenin-dependent
      chemiluminescence of phagocytizing macrophages. Stimulation with CdCl2, a MT
      inducer, for three days before the injury increased the levels of MT in
      macrophages but decreased its liver levels. This effect was accompanied by a
      decrease in the intensity of the luminol-dependent but not lucigenin-dependent
      chemiluminescence. Administration of CdCl2 after the injury facilitated the
      induction of reduced MT in liver cells; however, its levels in macrophages
      remained low, and the intensity of their chemiluminescence did not decrease. The
      data suggest that MT is involved in oxidative metabolism and regulation of
      macrophage activity after combined radiation and thermal injury.

PMID- 9275300
TI  - Inhibition of oxidation of aromatic amines in heme-containing hydrogen peroxide
      systems by substituted 4,6-di-tert-butyl-pyrocatechols.
AB  - The substituted pyrocatechols sodium (2,3-dihydroxy-4,6-di-tert-butyl-phenyl)-S
      thiosulfate (InH1) and 3-(S-glutathionyl)-4,6-di-tert-butyl-pyrocatechol (InH2)
      effectively inhibited oxidation of o-phenyle-nediamine and tetramethylbenzidine
      (TMB) catalyzed by hemin or its complex with BSA (methemalbumin). The method of
      competitive reactions of aromatic amines (PDA, TMB) and pyrocatechols (InH1,
      InH2) with active radicals was used for the quantitative determination of rates
      of radical initiation in systems containing hemin (methemalbumin) and H2O2
      (TBHP). The use of the inhibitor method for heme-protein-peroxide systems is
      complicated by heterogeneity of the radicals generated (HO., RO., HO2., RO2.,
      peroxide-like compounds I and II), formation of complexes of the inhibitors with
      protein component, and possible interaction of active radicals with organic co
      solvents (DMF or DMSO). The system hemin (methemalbumin)-H2O2 (TBHP)-aromatic
      amines can be used for testing the efficacy of potential bioantioxidants.

PMID- 9275302
TI  - Site-specific DNA-methylase M.BspST5I methylates only one strand of the
      recognized site.
AB  - We recently isolated a site-specific adenine DNA-methylase, M.BspST5I, which
      methylates only one strand of the recognized site GCATC. The methylated base is
      indicated by an asterisk.

PMID- 9275303
TI  - Inhibitor analysis of LDL-induced platelet aggregation.
AB  - Oxidized low density lipoproteins (oxLDL) bounded to specific receptors on the
      platelet surface are able to activate platelets. However, the exact mechanism of
      signal transduction from LDL receptors into the cell still requires
      investigation. In the present paper inhibitors of the main enzymes of known
      platelet activation pathways were used to investigate the mechanism of the LDL
      induced platelet aggregation. Our experiments were performed with autoxidized LDL
      (2-thiobarbituric acid reactive substances < 8 nmoles/mg). We demonstrated that
      the main enzymes of the arachidonate cycle do not play an important role in LDL
      induced platelet aggregation, whereas inhibition of protein kinase C and
      phospholipase C--principal enzymes of the phosphoinositide cycle--resulted in the
      inhibition of LDL-induced platelet aggregation in a dose-dependent manner. It was
      also shown that transmembrane calcium transport was necessary for LDL-induced
      platelet activation. Thus, we conclude that the phosphoinositide cycle is the
      main mechanism of cellular signal transduction during LDL-induced platelet
      activation.

PMID- 9275304
TI  - Purification of soluble and membrane forms of somatic angiotensin-converting
      enzyme by cascade affinity chromatography.
AB  - Soluble and membrane forms of angiotensin-converting enzyme were purified by
      cascade affinity chromatography. The enzyme forms were completely separated from
      each other using their different affinity to the hydrophobic matrix phenyl
      silochrome. The enzymes was further purified on affinity sorbent prepared by
      immobilization of the enzyme inhibitor N-[1(S)-carboxy-5
      aminopentyl]glycylphenylalanine on agarose. The procedure yielded
      electrophoretically homogeneous soluble and membrane forms of angiotensin
      converting enzyme containing only active molecules as demonstrated by titration
      with the reversible inhibitor lisinopril. According to phase separation in the
      presence of Triton X-114, the membrane enzyme is more hydrophobic than the
      soluble form. The catalytic characteristics of the enzyme forms differed from
      each other in the system Aerosol OT-water-octane (reversed micelles) which is
      model for the membrane environment of the enzymes in vivo.

PMID- 9275305
TI  - Thiolsubtilisin as an instrument for peptide synthesis. Preparation and
      properties.
AB  - A convenient procedure for thiolsubtilisin purification from an admixture of
      subtilisin involving affinity chromatography on bacitracin-Sepharose is
      presented. Thiolsubtilisin activity was measured by hydrolysis of p-nitrophenyl
      acetate, p-nitroanilide-peptide (Glp-Ala-Ala-Leu-pNA), and azocasein. The
      thiolenzyme catalyzes peptide synthesis. Under these conditions only activated
      peptide esters, e.g., p-chlorophenyl, N-hydroxysuccinimide, or p-nitrophenyl
      esters form peptide bonds during interaction with appropriate nucleophiles such
      as peptides and their derivatives and amino acid amides.

PMID- 9275306
TI  - Stability and stabilization of recombinant peroxidase in reversed micelles.
AB  - Stability of recombinant peroxidase lacking carbohydrate residues on the surface
      of the protein molecule has been characterized in reversed micelles of Aerosol OT
      in octane. The enzyme stability was found to depend on the surfactant hydration
      degree (w0 = [H2O]/[AOT]). Residual activity after 1 h incubation dropped to zero
      at w0 = 7 but was 54% at w0 = 25. However, the residual activity levels at all
      values of hydration degree were definitely low compared to that of glycosylated
      wild-type horseradish peroxidase. The stability of the enzyme apparently depends
      on the presence of carbohydrate residues. Stabilization of recombinant peroxidase
      in reversed micellar system involved sugar-containing co-surfactants such as
      Tweens and Spans is proposed. As an example, addition of 1 mM Span 80 (1%
      relative to AOT concentration) increased the recombinant peroxidase stability up
      to that of wild-type peroxidase.

PMID- 9275307
TI  - Anandamide and other N-acylethanolamines in mouse peritoneal macrophages.
AB  - N-acyl phosphatidylethanolamine (N-acyl PE) and free N-acylethanolamine (NAE) in
      mouse peritoneal macrophages were identified and quantified by gas chromatography
      mass spectrometry (GC-MS) of tertbutyldimethylsilyl derivatives in the presence
      of internal standards synthesized from [1,1,2,2-2H4]ethanolamine. N-acyl PE was
      present at a level of 123-187 pmol/mumol lipid P (521-768 pmol/10(8) cells), with
      arachidonic acid making up about 3-4% of the N-acyl moieties. NAE, on the other
      hand, was present at a level of only 17-30 pmol/mumol lipid P (70-121 pmol/10(8)
      cells), with N-arachidonoylethanolamine (anandamide) making up less than 1% of
      total NAE. Use of deuterium labeled internal standards and optimization of GC-MS
      conditions makes it possible to detect as little as 0.1 ng of saturated and 1 ng
      (3 pmol) of polyunsaturated NAEs in a lipid extract. The present method can be
      used to determine agonist-induced changes in the levels and compositions of N
      acyl PE and NAE.

PMID- 9275308
TI  - The interaction of lower alcohols with apoB in spin labeled human plasma low
      density lipoproteins (LDL).
AB  - In this study the interaction of alcohol with the macromolecular lipid-protein
      assembly represented by human plasma low density lipoproteins (LDL) was
      investigated. The spin label which covalently binds to the side chain amino group
      of lysines as well as terminal amino groups was attached to the spin labeled
      apoprotein (apoB) of native LDL in order to observe the protein component in the
      electron spin resonance (ESR) spectrum. The interaction of different lower
      alcohols (methanol, ethanol, propanol and butanol) with the spin labeled LDL was
      studied for two alcohol concentrations (0.3 and 3.0 M). The ESR spectra indicate
      a decrease of the hyperfine splitting and narrowing of the linewidth upon the
      action of alcohol that leads to the conclusion that alcohol provokes a change in
      the apoB conformation. These findings are explained by following the arguments of
      the phospholipid mediated mechanism of alcohol action, through the modulation of
      the lipid packing free volume which results in the protein conformational change.

PMID- 9275310
TI  - Improvement of enantioselective syntheses and chiral high resolution gas
      chromatographic analyses of (+)-2-allyl-2-carboethoxy-cyclopentanol.
AB  - The improvement of the biocatalytic reduction of 2-allyl-carboethoxy
      cyclopentanone (2) to the corresponding cyclopentanol derivative (+)-(1R,2R)-(1)
      was accomplished employing baker's yeast in organic media. This chiral
      cyclopentanol derivative (1), analyzed by high resolution gas chromatography
      performed over beta-cyclodextrin stationary phase, was obtained in 38% yield (>
      99% e.e.).

PMID- 9275309
TI  - Lipid peroxidation in presence of ebselen.
AB  - Lipid peroxidation is initiated by cell damage. After homogenisation of porcine
      heart tissue in aqueous solution we observed the same lipid peroxidation products
      as detected after heart infarction. We used this observation to study the
      influence of ebselen (2-phenyl-1,2-benzoisoselenazol-3-(2H)-one) on the
      generation of oxidatively derived monohydroxy fatty acids and alpha
      hydroxyaldehydes, typical lipid peroxidation (LPO) products. Heart tissue was
      homogenised before and after enzyme destruction and with addition of ebselen. The
      obtained LPO products were analysed by GC/MS after appropriate derivatisation and
      quantified by using internal standards. The amount of monohydroxy fatty acids and
      alpha-hydroxyaldehydes increased considerably in the porcine heart homogenates in
      which the enzymes were kept active. Addition of ebselen caused an additional
      significant increase of hydroxy fatty acids, while the increase of aldehydic
      compounds was less. These results confirm the glutathione peroxidase-like
      activity of ebselen but demonstrate also that it does not prevent lipid
      peroxidation.

PMID- 9275311
TI  - Chiral assay of atenolol present in microdialysis and plasma samples of rats
      using chiral CBH as stationary phase.
AB  - Two different enantioselective chiral chromatographic methods were developed and
      validated to investigate the disposition of the beta 1-receptor antagonist
      atenolol in blood and in brain extracellular fluid of rats (tissue dialysates).
      System A for the plasma samples was a one-column chromatographic system with a
      chiral CBH column with an aqueous buffer as mobile phase into which cellobiose
      was added for selective regulation of the retention of the internal standard, (S)
      metoprolol. The plasma samples were analysed after a simple extraction procedure.
      The limit of quantitation was 0.2 micrograms/ml for the atenolol enantiomers. The
      repeatability of the medium concentration quality control plasma sample (6.0
      micrograms rac-atenolol/ml) was 11-18% for the enantiomers. The dynamic linear
      range of the plasma samples was 0.5-20 micrograms/ml. For system B, since
      atenolol is an extremely hydrophilic drug, the tissue dialysate sample required a
      much more sensitive system as compared to the plasma samples. A coupled column
      system was used for peak compression of the enantiomers in the eluate after the
      separation on the Chiral CBH column, hence increasing the detection sensitivity.
      The limit of quantification was 0.045 micrograms/ml for the atenolol enantiomers
      in artificial CSF. The repeatability of the medium concentration quality control
      samples (0.1 and 4.0 micrograms rac-atenolol/ml in artificial CSF and Hepes
      Ringer, respectively) was 2.8-9.3% for the two enantiomers. The dynamic linear
      range of the brain samples was 0.05-1.0 and 0.5-20 micrograms/ml in artificial
      CSF and Hepes Ringer, respectively.

PMID- 9275312
TI  - Improved chromatographic performance of a modified human albumin based stationary
      phase.
AB  - Derivatization of the free cys34 in human serum albumin (HSA) anchored to a
      silica matrix has been performed by in situ reaction with ethacrynic acid. This
      modification, which is reported to occur under physiological conditions, gives
      rise in practice to a new column with different binding properties with respect
      to the column based on the native protein. Significant differences were observed
      in the binding of drugs known to bind to site I, (R)-(S)-warfarin and
      phenylbutazone, and to site II, 1,4-benzodiazepin-2-ones and nonsteroidal anti
      inflammatory agents. In particular, the chromatographic retentions markedly
      decreased for most of the drugs, and, in the case of chiral compounds,
      significant differences were often observed in the behavior of the two
      enantiomers, with higher values of enantioselectivity obtained for some of the
      examined compounds. Furthermore, the noncovalent binding of ethacrynic acid to
      the protein modifies the binding properties of the albumin.

PMID- 9275313
TI  - Chiral recognition by the copper(II) complex of 6-deoxy-6-N-(2
      methylaminopyridine)-beta-cyclodextrin.
AB  - A modified beta-cyclodextrin bearing a 2-aminomethylpyridine binding site for
      copper(II) (6-deoxy-6-[N-(2-methylamino)pyridine)]-beta-cyclodextrin, CDampy) was
      synthesized by C6-monofunctionalization. The acid-base properties of the new
      ligand in aqueous solution were investigated by potentiometry and calorimetry,
      and its conformations as a function of pH were studied by NMR and circular
      dichroism (c.d.). The formation of binary copper(II) complexes was studied by
      potentiometry, EPR, and c.d.. The copper(II) complex was used as chiral selector
      for the HPLC enantiomeric separation of underivatized aromatic amino acids.
      Enantioselectivity in the overall stability constants of the ternary complexes
      with D- or L-Trp was detected by potentiometry, whereas the complexes of the Ala
      enantiomers did not show and difference in stability. These results were
      consistent with a preferred cis coordination of the amino group of the ligand and
      of the amino acid in the ternary complexes ("cis effect"), which leads to the
      inclusion of the aromatic side chain of D-Trp, but not of that of L-Trp. In Trp
      containing ternary complexes, the two enantiomers showed differences in the
      fluorescence lifetime distribution, consistent with only one conformer of D-Trp
      and two conformers of L-Trp, and the latter were found to be more accessible to
      fluorescence quenching by acrylamide and KI.

PMID- 9275314
TI  - Stereoselective pharmacokinetics of ibuprofen in rats: effect of enantiomer
      enantiomer interaction in plasma protein binding.
AB  - Stereoselective pharmacokinetics of ibuprofen (IB) enantiomers were studied in
      rats. Unidirectional conversion from R-ibuprofen (R-IB) to S-ibuprofen (S-IB) was
      observed following intravenous administration. S-IB concentrations in plasma
      following racemate administration were simulated according to a conventional
      compartmental model using the parameters obtained after the administration of
      individual enantiomers, and resulted in overestimation of S-IB concentrations.
      Binding of IB enantiomers measured in rat plasma was stereoselective, the binding
      of R-IB being more favorable than that of S-IB. Moreover, there are interactions
      between IB enantiomers in binding, which may cause the increase of distribution
      volumes of IB enantiomers in the presence of their antipodes. Hence simulated S
      IB concentrations according to a conventional compartment model were
      significantly greater than those observed. Indeed, when the enantiomer-enantiomer
      interactions were taken into account, simulation of S-IB concentrations in plasma
      following racemate administration was in good agreement with observed values.
      Therefore, interactions between stereoisomers as well as dispositional
      stereoselectivity have to be considered when pharmacokinetics of stereoisomers
      after administration of the racemate are compared to those after administration
      of individual isomers.

PMID- 9275315
TI  - O-methylation of (+)-(R)- and (-)-(S)-6,7-dihydroxy-1-methyl-1,2,3,4
      tetrahydroisoquinoline (salsolinol) in the presence of pig brain catechol-O
      methyltransferase.
AB  - (+)-(R)- and (-)-(S)-salsolinol, dopamine-derived tetrahydroisoquinolines, were
      tested as substrates of pig brain soluble and membrane-bound catechol-O
      methyltransferase (COMT) and as inhibitors of O-methylation of dopamine by
      soluble COMT in vitro. Methylation products were separated by high-performance
      liquid chromatography with electrochemical detection. Quantification of the
      products showed that O-methylation of (+)-(R)-salsolinol by soluble COMT afforded
      the 7-O-methylated product salsoline preferentially, whereas (-)-(s)-salsolinol
      yielded almost equivalent amounts of the 6- and 7-methyl ethers. Unlike O
      methylation by soluble COMT, 7-O/6-O-methylation ratio produced by membrane-bound
      COMT varied with (+)-(R)-salsolinol concentration. As to the O-methylation of
      dopamine by soluble COMT, comparable competitive inhibition was observed with
      both (+)-(R)- and (-)-(S)-salsolinol.

PMID- 9275316
TI  - Reversible binding interactions between the tryptophan enantiomers and albumins
      of different animal species as determined by novel high performance liquid
      chromatographic methods: an attempt to localize the D- and L-tryptophan binding
      sites on the human serum albumin polypeptide chain by using protein fragments.
AB  - The stereoselectivity of the reversible binding interactions between the D- and L
      tryptophan enantiomers and serum albumins of different animal species and
      fragments of human serum albumin (HSA) was investigated by applying three novel
      high performance liquid chromatographic (HPLC) arrangements. The separations were
      performed by means of 1) an achiral (diol-bond), 2) a chiral (bovine serum
      albumin-bond) silica gel sorbent, and 3) a column switching technique which uses
      both the diol- and HSA-bond HPLC stationary phases. A polarimetric detector
      and/or an ultraviolet (UV) spectrophotometer were used to monitor the separation
      process. HPLC arrangement 3 allowed the evaluation of enantioselective binding
      for D- and L-tryptophan to different albumins and albumin fragments. At present,
      column switching can be considered the technique of the broadest applicability
      for investigating the reversible binding interactions between a protein and drug
      enantiomers.

PMID- 9275318
TI  - Current situation of sexually transmitted Chlamydia trachomatis infections in
      China.

PMID- 9275319
TI  - Strategies of myocardial protection during cardiac surgery.

PMID- 9275320
TI  - Hypertension with identifiable cause. Secondary hypertension.

PMID- 9275321
TI  - A preliminary study on immune response to hepatitis E virus DNA vaccine in mice.
AB  - OBJECTIVE: In order to elicit immune response to hepatitis E virus (HEV) with the
      method of direct injection of naked DNA. METHODS: The gene encoding the
      structural protein of pORF3, a Chinese strain of HEV, was cloned into the
      eukaryotic expression plasmid pSVL. The resulted plasmid pSVL-HEV ORF3 was used
      as HEV DNA vaccine, to inoculate Balb/c mice intramuscularly with a dose of 100
      micrograms. Mice injected with empty pSVL DNA served as control. RESULTS: After 1
      2 times inoculation, twelve of 16 mice inoculated with pSVL-HEV ORF3 had anti-HEV
      IgG seroconversion. pSVL-HEV ORF3 was still detectable in the muscle of the
      inoculated mice 18 days after the injection, by the method of PCR. None of the
      control group had a detectable level of anti-HEV IgG. It is also found that the
      humoral immune response to HEV induced by DNA vaccine could be boostered by HEV
      recombinant fusion protein. CONCLUSION: Our present study demonstrated that
      nucleic acid vaccine is able to prime a specific humoral immune response to HEV
      in mice.

PMID- 9275322
TI  - Overexpression of c-myc gene without gene amplification in human hepatocellular
      carcinoma.
AB  - OBJECTIVE: To clarify the relationship between c-myc gene amplification and
      expression in human hepatocellular carcinoma (HCC) tissue. METHODS: Levels of
      amplification, transcription and P62 myc expression of c-myc gene in tumor
      tissues and corresponding non-tumor tissues were systematically studied using Dot
      blot hybridization, in situ hybridization and immunohistochemical technique,
      respectively. The 14 pairs of specimens were resected from patients with HCC.
      RESULTS: The amplification of c-myc gene was not found in tumor and non-tumor
      tissues. Overexpression of c-myc mRNA transcription was detected in 11 tumor
      tissues and 10 non-tumor tissues. The positive rate of P62 myc was 85.7% (12/14)
      in tumor tissues and 92.9% (13/14) in non-tumor tissues, respectively. A close
      correlation was noticed between c-myc mRNA and P62 myc expression. The results
      suggested that c-myc gene overexpression was not related to its amplification.
      CONCLUSIONS: The overexpression of c-myc mRNA and gene product without
      amplification may be characteristic in HCC.

PMID- 9275323
TI  - A study of time window for oxidative stress associated with myocardial ischemia
      and reperfusion.
AB  - OBJECTIVE: To investigate the time window for oxidative stress occurred in
      myocardial tissue and associated with reperfusion. METHODS: Thirty nine conscious
      rabbits were subjected to 0.5 hours (h) of myocardial ischemia and reperfusion
      for 0 h, 6 h, 24 h and 72 h, respectively, and nine rabbits served as controls.
      Activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-px) and
      myeloperoxidase (MPO), and contents of GSH and malondyaldehyde (MDA) were
      measured in myocardial tissues taken from ischemic non-necrotic area (INNA),
      ischemic necrotic area (INA) and non-ischemic area (NIA), respectively. RESULTS:
      The antioxidant status of INNA was weakened at 6th h, 24th h, and 48th h of
      reperfusion. Activities of Mn-SOD and Cu-Zu-SOD returned to normal value at 72nd
      h of reperfusion, but GSH-px activity and GSH content remained in lower value.
      MDA content had a marked increase at 6th h, 24th h, 48th/h and 72nd h of
      reperfusion. MPO activity had a progressive increase after reperfusion, with its
      peak value at 48th h, and PMN accumulation occurred mostly in necrotic zone and
      its outer board zone. A mild oxidative stress also occurred in non-ischemic
      tissue, but without obvious neutrophils infiltration. CONCLUSIONS: The time
      window for oxidative stress associated with myocardial ischemia and reperfusion
      lasts for at least 72 h, and PMN infiltration is one of the most important
      factors of delayed myocardial reperfusion injury.

PMID- 9275324
TI  - The efficiency of respiratory muscle strengthening training programs in pilots.
AB  - OBJECTIVE: To evaluate the efficiency of respiratory muscle training programs in
      pilots. METHODS: Twenty-four male pilots were divided into two groups. The
      training group (12 pilots) underwent respiratory strengthening training programs
      besides routine physical exercises. The other 12 pilots in the control group only
      did routine physical exercises, but the training time was the same in these two
      groups. Before and after training programs in the two groups, the respiratory
      muscle functions were examined. RESULTS: 24 pilots in these two groups completed
      training programs within four weeks. The pilots in the training group got
      improvement of respiratory muscle functions which was much better than those of
      the control group. CONCLUSION: It suggests that the strengthening training
      programs of respiratory muscles can improve and strengthen the respiratory muscle
      functions in pilots.

PMID- 9275325
TI  - Relationship between high incidence of adverse dapsone reactions and slow
      acetylate phenotype or low plasma/lymphocyte glutathione level.
AB  - OBJECTIVE: To investigate the relationship between high incidence of adverse
      dapsone reactions in acquired immunodeficiency syndrome (AIDS) patients and slow
      acetylate phenotype or low plasma/lymphocyte glutathione level of these patients.
      METHODS: Twenty-one cases of advanced AIDS patients (CD4 < 200/microliter) were
      involved in this study, all Europeans except one black, were acetylate phenotyped
      via analysis of caffeine metabolites, named 5-Acetylamino-6-formylamino-3
      methyluracil, 1-Methylxanthine and 5-Acetylamino-6-amino-3-methyluracil, in human
      urine collected 2 hours after a cup of caffeine-spiked coffee and their
      plasma/lymphocyte glutathione concentrations were determined, by high performance
      liquid chromatographic method. RESULTS: Of the 21 AIDS patients, 15 are slow
      acetylators, accounting for 74.8%. One of 6 rapid acetylators has adverse dapsone
      reactions, acounting for 17%, compared with 46% for slow acetylators (7/15). The
      concentrations of glutathione in plasma/lymphocyte (6.97 +/- 0.95 mumol and 28.75
      +/- 2.78 nmol/mg protein) in AIDS patients with adverse dapsone reactions are
      significantly lower than those (10.90 +/- 1.45 mumol and 32.15 +/- 2.21 nmol/mg
      protein) of AIDS patients without adverse dapsone reactions, and also than those
      (11.85 +/- 1.83 mumol and 33.76 +/- 2.32 nmol/mg protein) of health controls.
      CONCLUSIONS: Slow acetylators, which lead to accumulation of toxic dapsone
      metabolites and those subjects who are lower in glutathione level in
      plasma/lymphocyte because of certain kind of diseases as advanced AIDS are risk
      population of adverse dapsone reactions. Routinely determining human acetylate
      phenotype status might be helpful in adjusting and modifying dapsone dosage
      regimen.

PMID- 9275326
TI  - Simultaneous bilateral total knee arthroplasty for rheumatoid arthritis.
AB  - OBJECTIVE: To study the result of one staged bilateral total knee arthroplasty
      (TKA) operation under epidural anesthesia on patients with severe rheumatoid
      arthritis (RA). METHODS: From April 1987 to December 1992, simultaneous bilateral
      TKA was performed on 45 patients (90 knees), including 41 patients with RA, 3
      with juvenile RA, and 1 with Sjogren syndrome. The mean follow-up period was 63
      months. RESULTS: Improved function and pain relief were noted in all patients.
      There were no wound healing problems. Thrombophlebitis was observed in few cases.
      Late infection rate was 5.6% (5 knees) and aseptic loosening was revised on 5
      knees. CONCLUSIONS: Simultaneous bilateral TKA is not only a procedure of low
      cost, saving blood, reducing anesthesia risk, drugs' side effect and
      hospitalization, but also facilitates early rehabilitation. Except for late
      infection, there is no increase in complications.

PMID- 9275327
TI  - Spontaneous malignant transformation of fibrous dysplasia.
AB  - OBJECTIVE: To evaluate the clinical and radiological findings in diagnosing
      spontaneous malignant transformation of fibrous dysplasia. METHODS: Fifteen cases
      of sarcomatous transformation proved by operation and pathological examinations
      were found in a group of 356 patients with fibrous dysplasia, and their
      radiological manifestations were retrospectively studied. The 15 cases included 8
      osteosarcomas, 5 fibrosarcomas and 2 chondrosarcomas. All the 15 patients were
      known to have long-standing fibrous dysplasia, but no radiation therapy was ever
      received. Eleven patients had polyostotic fibrous dysplasia and 4 had monostotic
      type. RESULTS: Malignant transformation most frequently occurs in the cystic
      expansive lesion of the long tubular bone. Pains, swelling and late appearance of
      a bony mass are the main clinical manifestations. The early radiological features
      of sarcomatous transformation in fibrous dysplasia are moth-eaten or cystic areas
      of osteolysis located in the involved bone. The cortical destruction and gradual
      formation of a soft tissue mass that contains tumor-bone are highly suspicious of
      osteosarcomatous transformation, while ring-like and spotty calcification in the
      tumor matrix is indicative of chondrosarcoma. Fibrosarcoma usually shows simple
      osteolytic destruction. CONCLUSIONS: According to the clinical radiological
      findings, patients of sarcomatous transformation can be detected in the early
      stage. These radiological findings may be used as a clue for differentiating
      various kinds of sarcomatous transformation.

PMID- 9275329
TI  - A case of diffuse panbronchiolitis.

PMID- 9275328
TI  - Analysis of thymoma excision in patients with myasthenia gravis.
AB  - OBJECTIVE: To study the clinical characteristics of myasthenia gravis (MG) with
      thymoma and the effect of tracheostomy at the early stage after operation.
      METHODS: Thymoma excision and selective tracheostomy were performed on 46
      patients with MG from March 1983 to December 1994. RESULTS: There were 15
      patients with benign thymomas and 31 patients with malignant thymomas. MG crises
      were seen in 52.2% of patients postoperatively, most in type IIb and III. The
      mortality of in-patients after operation was 10.9%. Thirty-nine patients with
      thymoma were followed up for 6 months to 12 years after being discharged from
      hospital. The MG symptoms were relieved in 33.3%, improved in 20.5% and unchanged
      in 2.6% of patients. 38.5% of patients died of the disease. CONCLUSION: The
      characteristics of MG with thymoma are, more severe condition of the patient,
      rapid advance, and more MG crises before and after operation. The perioperative
      mortality from MG with thymoma is higher and its prognosis is unfavourable. It is
      very important to treat severe cases of MG with thymoma by tracheostomy with
      thymoma excision at the early stage after the operation. This is an effective
      method to prevent and treat MG crises as well as to lower the perioperative
      mortality.

PMID- 9275330
TI  - The future pattern of surgical department and training of surgeons in community
      hospitals.

PMID- 9275331
TI  - Collaborative study on evaluation of immunodiagnostic assays in schistosomiasis
      japonica by treatment efficacy assessment. Collaboration Group.
AB  - OBJECTIVE: This paper is the summary of "National Symposium on the Value of
      Immunodiagnostic Assays in Schistosomiasis by Treatment Effects Assessment" which
      was directed by the Expert Advisory Committee for Schistosomiasis of the Ministry
      of Public Health. This symposium was held to evaluate the diagnostic effects of
      the new system of detection in the sensitivity and specificity by treatment
      assessment. MATERIALS AND METHODS: Twelve laboratories with 14 assay systems
      participated in this collaborative study, in which, 450 sera were detected by
      double blind trial using a classical antibody detection with ELISA as a control.
      RESULTS: The results showed that 6 test systems were superior or close to the
      classical antibody detection, especially in evaluating the value of treatment
      effects. CONCLUSIONS: It is unanimously recognized that much progress has been
      made in the research of immunodiagnosis of schistosomiasis in China, but many
      problems remain to be solved and worth further studying.

PMID- 9275332
TI  - Analysis of Chinese isolates of Trichinella spiralis by molecular biotechnology.
AB  - OBJECTIVE: To investigate the relationships among Trichinella spiralis isolates
      obtained from different hosts and geographical regions in China. MATERIALS AND
      METHODS: Six isolates of Trichinella spiralis obtained from Changchun, Tianjin,
      Xi'an, Henan and Yunnan were detected. All the isolates were collected from pigs
      or dogs. Restriction fragment length polymorphism (RFLP), isoenzyme
      electrophoresis and soluble protein analysis were used. RESULTS: Distinctive
      banding patterns in restriction maps were seen between Changchun and other
      isolates studied. A cloned specific repetitive DNA sequence (1.12 kb) from
      Changchun isolate was then selected to prepare probe for Southern blotting of DNA
      fragments. The hybridizing banding patterns among the isolates were different and
      only the Changchun isolate showed the 1.12 kb band. The Changchun isolate was
      also distinguishable from the other isolates in isoenzyme patterns of GP1, G6PD,
      HK, 6PGDH and AK, as well as in isoelectric focusing electrophoresis where the
      Changchun isolate presented a specific band at 4.1 P1. CONCLUSIONS: There are at
      least two different biological types of Trichinella spiralis in China and the
      differences between them may be attributed to different geographical origins
      and/or different hosts.

PMID- 9275333
TI  - The role of Leptotrombidium scutellare in the transmission of human diseases.
AB  - OBJECTIVE: To investigate the role of Leptotrombidium (L.) scutellare in the
      transmission of hemorrhagic fever with renal syndrome (HFRS) and tsutsugamushi
      disease of autumn-type. MATERIALS AND METHODS: Four criteria were used to
      ascertain this mite as transmitting vector of disease: (1) epidemiological
      evidence; (2) natural infection of pathogen; (3) ability to transmit pathogen via
      biting; (4) ability to transfer pathogen via transovarian route. RESULTS: The
      results indicated that L. scutellare was the dominant species of chigger mite on
      rats. Its seasonal distribution was correlated with the incidence of these two
      diseases. This mite could be naturally infected by HFRS virus (HFRSV) and
      Rickettsia tsutsugamushi (Rt) and the mite could transmit HFRSV and Rt to
      vertebrates by biting and to its offspring via transovarian transmission.
      CONCLUSIONS: These results have proved that L. scutellare can be a transmitting
      vector of HFRS and tsutsugamushi disease of autumn-type.

PMID- 9275334
TI  - Rat as an animal model carrying human hepatitis B virus in hepatocytes.
AB  - OBJECTIVE: To establish an experimental animal model of rat carrying human
      hepatitis B virus in the hepatocytes using a simple and reproducible method.
      MATERIALS AND METHODS: Human serum rich in hepatitis B virus was injected into
      portal veins and caudalis veins of young male Wistar rats. One and two months
      after the injection, liver biopsies were done. In situ hybridization and
      immunohistochemical study of liver specimens were carried out. Sera were also
      examined for HBV DNA by polymerase chain reaction. RESULTS: All of seven rats in
      this experiment were HBV DNA and HBV surface antigen (HBsAg) positive in their
      hepatocytes. Most HBV positive hepatocytes were distributed around the central
      vein and scattered in the liver lobules, and HBV DNA and HBsAg were located in
      cytoplasm. HBsAg exists mainly as the forms of diffuses and inclusion body. No
      hepatocytic damage or inflammation was observed. Neither viremia nor antigenemia
      was detected. CONCLUSIONS: Our studies showed for the first time that natural
      human HBV can enter Wistar rat liver cells through intravenous injection
      efficiently and express for a long period. This animal model can be used in the
      studies of HBV molecular biology, therapeutic regimens and prophylaxis against
      HBV. A possible mechanism of HBV entering rat hepatocytes is also proposed.

PMID- 9275336
TI  - Left ventricular diastolic dysfunction in patients with angina decubitus.
AB  - OBJECTIVE: To investigate the relationship between left ventricular diastolic
      dysfunction and episodes of angina decubitus. METHODS: The study population
      consisted of three groups, groups I (20 controls) had no cardiovascular diseases.
      Group II (20 patients) had coronary artery disease (CAD) without angina
      decubitus. Group III (24 cases with ejection fraction (EF) > 45%) were selected
      from 26 patients with angina decubitus. RESULTS: Left ventriculography (LVG)
      showed that left ventricular (LV) first 1/3 filling fraction (1/3FF) was
      significantly reduced in groups III as compared with groups II and I (P < 0.01).
      Left ventricular end-diastolic pressure (LVEDP) significantly increased in
      patients with angina decubitus after LVG as compared with that before LVG (P <
      0.01). However, there were no statistically differences in LVEDP, before and
      after LVG in both groups II and I. CONCLUSIONS: Patients with angina decubitus
      have abnormalities of LV diastolic filling and decrease in LV compliance.

PMID- 9275335
TI  - Structure and function of the band 3 Cl-/HCO3- transporter in chronic respiratory
      failure patients.
AB  - OBJECTIVE: To study red blood cell (RBC) membrane band 3 protein structure and
      anion transport function in cor pulmonale patients with respiratory failure.
      PATIENTS AND METHODS: Blood samples were obtained from 80 cases of cor pulmonale
      and 37 normal subjects (control group). The patients were divided into type I
      respiratory failure (Group I, n = 40) and type II respiratory failure (Group II,
      n = 40). The anion permeability of the erythrocyte membrane (Pcl), PO2 and PCO2
      in 12 of the patients with type II respiratory failure were observed in acute
      stage (AS), chronic stage (CS) and recovery stage (RS). Membrane protein was
      analyzed by polyacrylamide electrophoresis in SDS. 55-KDa membrane domain was
      fractionated on 10% NaDodSO4 polyacrylamide gel column and purified further with
      a sephadax G-25 column. The composition of amino acids was analyzed on a Beckman
      6300 Gold system amino acid analyzer. The Pcl was determined by the hypoisotonic
      hemolysis method. RESULTS: The relative content of band 3 protein erythrocytic
      membrane, anion permeability coefficient of the erythrocyte membrane and plasma
      chloride in the patients with cor pulmonale with type II respiratory failure were
      significantly lower than those in the patients with type I respiratory failure
      and the control. The number of residues in the anion transport domain of the
      trypsin fragment of 55,000 daltons of band 3 protein showed no significant
      difference among the three groups. CONCLUSIONS: The structure of anion transport
      sites remains intact and so the reduction of the anion transport function of band
      3 protein in patients with cor pulmonale with type II respiratory failure may be
      due to the decrease of the relative content of band 3 protein, the decrease of
      extraerythrocytic chloride and hypoxia.

PMID- 9275337
TI  - Effects of myocardial viability assessment with positron emission tomography on
      clinical management and patient outcomes.
AB  - OBJECTIVE: To evaluate the effects of myocardial viability assessment with
      positron emission tomography on cardiac revascularization decision-making and
      consequential outcomes of patients with multivessel coronary artery disease.
      METHODS: Thirty-three patients with multivessel coronary disease and heart
      failure were studied in this series, using 13NH for myocardial perfusion and F-18
      deoxy-glucose for myocardial metabolism. Viable myocardium (mis-matched perfusion
      metabolism) was visually and quantitatively analyzed in anterior, apical, septal,
      inferior, and lateral segments of the left ventricle. Left ventricular ejection
      fraction (LVEF) was also measured with first-pass radionuclide angiocardiography.
      RESULTS: Based on the assessment of myocardial viability, 19 patients (group A)
      with sufficient viable myocardium underwent revascularization (coronary bypass
      graft and/or angioplasty), and 14 patients (group B) without sufficient viable
      myocardium received conservative medical treatment. During an average of 17-month
      follow-up, there were 2 (10.5%) deaths in group A and 2 in group B (14.3%) deaths
      (P > 0.5). Patients with revascularization showed significantly improved average
      LVEFs post-revascularization, without revascularization procedure-related
      mortality; patients with medical treatment had an initial average LVEF of 25% and
      class II-III (NYHA) average cardiac function with a survival rate of 86% in
      average, which was better than that reported in literature. CONCLUSION: Positron
      emission tomography is useful in myocardial viability assessment for cardiac
      revascularization decision-making through precisely selecting suitable patients
      for revascularization and avoiding operations on those who will not benefit,
      which results in promising effects on outcomes of patients with multivessel
      coronary disease and severe left ventricular dysfunction.

PMID- 9275339
TI  - Approaches and reconstruction in skull base operation.
AB  - OBJECTIVE: To design convenient lateronasal and infrafrontal approaches or
      lateronasal subvolution approach to radically resect skull base tumors involving
      cranial cavity. METHODS: From 1987 through 1994, 22 patients with malignant
      tumors, 6 with benign tumors, one with a giant sphenoid sinus cyst and one with
      intranasal meningoencephalocele underwent the operation. Twenty-three cases had
      anterocranial fossa involved; 4, midcranial fossa; 2, anteromedial cranial fossa;
      and 1 case, posteromedial cranial fossa. Among the patients with malignant
      tumors, 11 underwent expansive maxillectomy and 10 had orbital contents resected.
      The intracranial approaches through lateronasal and infrafront (21 cases), nasal
      columella lateral subvolution (3 cases) and other approaches were used. RESULTS:
      The reconstruction of bony skull base defect in excess of 3.00 cm x 3.00 cm with
      total front musculocutaneous flap (8 cases), galeal and pericranial flap (5
      cases) or other tissues (3 cases) has effectively prevented meningoencephalocele.
      Twelve cases had the dura resected in a range of 2.00 cm x 2.00 cm to 7.00 cm x
      6.00 cm. Reconstruction of the dura defect with autofascia lata in 9 cases and
      other tissues in 3 cases effectively prevented the cerebrospinal fluid leak.
      Eight of 22 (36.4%) patients with malignant tumors have been alive and free of
      disease for 3-7 years after the operation. Six patients with benign tumors, one
      patient with giant sphenoid sinus cyst and one with meningoencephalocele were
      cured with this reconstructing method. CONCLUSIONS: Frontal musculocutaneous and
      pericranial flaps have advantages over free bone because of easy surviving and
      easy operating without occurrence of osteonecrosis and exclusive reaction.

PMID- 9275338
TI  - Study on ultrastructural cytochemistry and pathogenic mechanism of Trichomonas
      vaginalis.
AB  - OBJECTIVE: To study the relation among enzymic ultrastructural localizations,
      cell organelles and functions of Trichomonas vaginalis (T. vaginalis) as well as
      its pathogenic mechanism. MATERIAL AND METHODS: The specimens were Trichomonas
      vaginalis cultured purely for several generations. After prefixation, several
      electron microscopic cytochemical reactions for marker enzymes of lysosome, Golgi
      body, mitochondrion and microbody as well as Ur-Pb-Cu impregnation were
      undertaken. Then the specimens were post-fixed and embedded, and the unstained
      ultrathin sections were observed under a transmission electron microscope.
      RESULTS: The activities of acid phosphatase and cytidine monophosphatase appeared
      in the primary and secondary lysosomes of the parasite, and the reaction product
      of peroxidase was found in the secondary lysosomes. It was found that lysosomes
      could release hydrolytic enzymes out of the cell. The reaction products of
      thiamine pyrophosphatase and nicotinamide adenine dinucleotide phosphatase were
      located within the mature-surface and intermediate saccules of Golgi body
      respectively. The reactions for succinate dehydrogenase, cytochrome oxidase and
      catalase were negative. The hydrogenosomes, endoplasmic reticulum and Golgi
      bodies of the parasite were densely stained by Ur-Pb-Cu impregnation method.
      CONCLUSIONS: T.vaginalis has lysosomal system which can release hydrolases out of
      the parasite, causing damage to the vaginal and urethral epithelial cells. This
      may be an important pathogenic mechanism of vaginitis and urethritis caused by
      T.vaginalis. This protozoon has well-developed Golgi bodies and rich endoplasmic
      reticulum. It lacks mitochondrion and microbody, but has abundant hydrogenosomes
      which are energy producing organelles of anaerobic metabolism and resemble
      microbody in morphology and mitochondrion in some functions.

PMID- 9275340
TI  - Osteoclastic resorption of Haversian systems in cortical bone of femoral neck in
      aged women. A scanning electron microscopic study.
AB  - OBJECTIVE: To reveal the sequence of events of osteoclastic resorption taking
      place in the cortical bone of the femoral neck in aged women. MATERIAL AND
      METHODS: The cross sections of cortical bones of the femoral neck from 7 aged
      women who underwent endoprosthetic replacement for intracapsular hip fracture,
      were processed and subjected to scanning electron microscopic observation.
      RESULTS: The cortical bone sections revealed enlargement of the Haversian canals.
      On the inner linings of the enlarged canals many oval resorption lacunae could be
      found, reflecting osteoclastic resorption of the Haversian systems. The
      osteoclastic resorption with subsequent enlargement of the Haversian canals into
      round or oval cavities took place first over the inner portions of the cortical
      sections, thereby rendering these areas porotic (cancellization). These processes
      of the Haversian systems and canals then gradually emerged over the central and
      eventually over the outer areas of the cortical bone, and the entire cortical
      bone became porotic. Meanwhile, the inner porotic portion of the cortex turned
      into trabeculae (trabecularization) and became gradually resorbed, resulting in
      thinning of the medial cortex. CONCLUSIONS: Cortical cancellization,
      trabecularization and thinning compromised the material strength of the femoral
      neck so that fracture would ensue even with trivial injury.

PMID- 9275342
TI  - Rapid HLA-DR genotyping by PCR-amplification with sequence-specific primers.
AB  - OBJECTIVE: To establish a rapid genotyping for HLA-DR alleles by polymerase chain
      reaction with sequence-specific primers (PCR-SSP) for clinical application.
      MATERIAL AND METHODS: The subjects of study included 69 recipients, 43 unrelated
      donors and 5 cell lines. Genomic DNA was prepared from peripheral blood
      leukocytes by a salting-out method. Thirty primers were designed according to the
      HLA-DRB nucleotide sequences, and synthesized on a 391 DNA synthesizer. Twenty
      separate PCR reactions were performed for each sample. The amplification was
      accomplished by 34 cycles consisting of denaturation at 94 degrees C for 30
      seconds, annealing at 60 degrees C for 50 seconds and extension at 72 degrees C
      for 40 seconds. The specificity of matching was determined by standard DNAs and
      Southern hybridization using DIG labeling probes. RESULTS: All 112 samples and 5
      cell lines were able to be typed by PCR-SSP. No false positive or false negative
      typing results were obtained. The reproducibility was 100%. The size of the
      specific product was in concordance with the size of the designed primers. The
      overall time for genotyping was 4 hours. The typing results were confirmed by
      Southern hybridization. CONCLUSIONS: Genotyping for HLA-DR by PCR-SSP is a rapid
      and accurate matching technique suited for clinical application.

PMID- 9275341
TI  - Polymorphonuclear leukocyte-mediated bone degradation and influence of blood
      mononuclear cells on the mouse calvarial model.
AB  - OBJECTIVE: To investigate the relationships between degradation of bone and
      activated blood polymorphonuclear leukocytes (PMNL) and mononuclear leukocytes
      (ML) as well as their soluble products in vitro. MATERIALS AND METHODS: A
      neonatal mouse calvarial bone model was used to assess the activity of
      degradation (by measuring the amount of 45Ca release) by normal human blood
      leukocytes, separated PMNL and ML following 24-hour incubation. The effects of
      conditioned culture medium obtained from Staphylococcus aureus-stimulated ML on
      PMNL-mediated calvarial bone loss were also studied. RESULTS: It was demonstrated
      that isolated human PMNL rapidly degraded bone in a dose and time dependent
      manner. The PMNL-mediated bone degradation was enhanced by conditioned medium
      obtained from Staphylococcus aureus-stimulated ML. CONCLUSION: These findings
      implicate PMNL as major contributors to early bone loss in infectious diseases
      such as acute haematogenous osteomyelitis.

PMID- 9275343
TI  - MR evaluation of the brain in central diabetes insipidus.
AB  - OBJECTIVE: To evaluate the role of magnetic resonance (MR) imaging in determining
      the cause of central diabetes insipidus (CDI) by using MR imaging to describe the
      findings in the hypothalamic-pituitary area in patients with CDI. METHODS: Thirty
      one cases of clinically proved CDI were prospectively studied. A control study
      was also conducted in 200 normal subjects. MR imaging was performed on a 1.0 T
      superconductive unit with T1-weighted images obtained in the sagittal, coronal
      and axial planes. RESULTS: Hypothalamic-pituitary masses or structural changes
      were identified in 26 cases and normal structures in 5. The normal high signal
      intensity of the posterior pituitary lobe was absent in 29 cases, but remained
      unchanged in 2. In the control group, the frequency of the high signal of the
      posterior lobe was 93%. CONCLUSIONS: The absence of the normal high signal in the
      posterior pituitary lobe is closely related to the loss of hypothalamic-pituitary
      function. MR imaging is very sensitive in demonstrating the changes in this area
      in CDI and it can provide an accurate diagnosis when combined with the clinical
      information.

PMID- 9275344
TI  - A one-hand operation gun for transrectal prostate biopsy.
AB  - OBJECTIVE: To develop a new automatic biopsy device (ABD) that enables a
      radiologist to obtain multiple samples with one hand and free the other hand to
      handle the ultrasonic scanner for continuous monitoring. MATERIALS AND METHODS:
      The new ABD developed by us in April 1994 enabled a radiologist to complete all
      the biopsy procedures including loading and reloading the spring system, firing
      the device, emptying the specimen, selecting the depth of needle advancement, and
      multiple sampling, simply by pressing 3 buttons in turn with his/her right thumb.
      Using this new ABD, transrectal prostate biopsy under the guidance of transrectal
      ultrasonic imaging was performed in 60 consecutive cases of prostate diseases.
      Each biopsy procedure was completed by a single radiologist, who was able to
      obtain multiple specimens with one biopsy needle, using only one hand and freeing
      the other hand for the manipulation of the ultrasonic scanner for guidance.
      RESULTS: A total of 265 satisfactory core tissue specimens of 285 needle passes
      (93%) were obtained from the 60 patients. Definite pathologic diagnoses were made
      for all the 60 patients (100%). No serious biopsy-related complications were
      observed. The main complications were hematuria in 24 of 60 (40%) patients and
      fever in 5 (8.3%). CONCLUSION: On the basis of our experience with the 60
      patients, this new ABD can be operated smoothly and effectively with the right
      hand, while the left hand is freed to handle the ultrasonic transducer for
      continuous monitoring.

PMID- 9275345
TI  - Association of pituitary adenoma with intracranial arteriovenous malformation.

PMID- 9275346
TI  - Suppression of cell-mediated immunity due to immune deviation.

PMID- 9275347
TI  - Recent advances of otology in China.

PMID- 9275348
TI  - Endoscopic Intranasal dacryocystorhinostomy in forty-five patients.
AB  - OBJECTIVE: To observe the results of endoscopic intranasal dacryocystorhinostomy.
      METHODS: Forty-five patients (forty-eight eyes) suffering from chronic
      dacryocystitis received endoscopic intranasal dacryocystorhinostomy after
      November 1991, and were followed up for 3 to 36 months. RESULTS: Thirty-nine eyes
      were cured (81.2%). It is significantly effective (8.3%) in 4 eyes, and effective
      in 2 eyes (4.2%). The total effective rate was 93.7%. CONCLUSIONS: The intranasal
      approach is simple causing little bleeding and no facial scar. With the self-made
      dacryocyst-illuminator (diameter = 0.8 mm), and by transilluminating the lacrimal
      sac with fiberoptic intraocular endoilluminator bundle, the sac can be located
      endonasally, thus facilitating the approach.

PMID- 9275349
TI  - Functional motor innervation of brachial plexus roots. An intraoperative
      electrophysiological study.
AB  - OBJECTIVE: To study the functional motor innervation of C5-T1 nerve roots of the
      brachial plexus electrophysiologically. PATIENTS AND METHODS: The
      electrophysiological properties of normal brachial plexus roots and their
      functional motor innervation were examined in 15 patients with brachial plexus
      injuries, while the contralateral healthy side C7 root transfer was operated on.
      Different nerve roots of the brachial plexus were stimulated and maximum
      amplitudes were recorded in the following 12 muscles: deltoid, biceps,
      infraspinatus, brachiaradialis, flexor carpi radialis, triceps, extensor
      digitorum communis, latissimus dorsi, flexor digitorum profundus, abductor
      brevis, abductor digiti minimi and flexor carpi ulnaris. RESULTS: Functional
      motor innervation of brachial plexus roots showed the following results: a. C5
      mainly forms the axillary nerve to innervate deltoid muscle; b. C6 mainly
      constructs the musculocutaneous nerve to innervate biceps muscle; c. C7 mainly
      forms the radial nerve to innervate triceps muscle; d. C8 mainly forms the median
      nerve to innervate the flexor digitorum muscle; e. T1 mainly forms the ulnar
      nerve to innervate the intrinsic muscles of the hand. CONCLUSIONS: The brachial
      plexus is functionally divided into three groups: C5, 6 innervate shoulder and
      elbow; C8T1 innervate the hand; and C7 innervates shoulder, elbow, wrist and
      hand. Theoretically, any division of the nerve root alone may not cause damage to
      limb function.

PMID- 9275350
TI  - P53 gene abnormalities in osteosarcoma.
AB  - OBJECTIVE: The P53 tumor suppressor gene shows the most frequent genetic
      alteration in human tumors. Mutation, deletion and rearrangement of P53 gene have
      been found in several types of neoplasm including osteosarcoma. The present study
      is to clarify the status of abnormalities of this gene in osteosarcoma in China.
      MATERIALS AND METHODS: Forty-six osteosarcomas were collected from 32 male and 14
      female patients aged 20.6 years on average. Eight patients had lung metastasis.
      Immunohistochemistry, Southern blot and contrast flow cytometry were used for the
      study. RESULTS: Twenty-seven of 46 (58.7%) osteosarcoma specimens showed strongly
      positive reaction to the MoAb BP53-12 staining (+2 - +3), which indicated
      overexpression of P53 protein in osteosarcoma. Contrast study with DNA flow
      cytometry made on osteosarcoma showed that most of the tumors with strongly
      positive P53 have higher DNA content than those of negative ones. Alterations of
      the restriction pattern of the P53 gene were detected in 4 of 20 osteosarcomas in
      the Hind III group and 3 of 24 in the Eco R I group. Three of them were part or
      whole deletion of the gene and five of them had extraband which indicated
      rearrangement of the gene. CONCLUSIONS: The results of this study showed that
      overexpression of P53 oncoprotein is one of the most frequent genetic changes in
      osteosarcoma and P53 oncoprotein expression analysis could be a prognostic
      parameter in osteosarcoma. P53 gene abnormalities play an important role in the
      development of transformation and proliferation of osteosarcoma cells.

PMID- 9275351
TI  - Microsurgery of intramedullary cervical cord tumor.
AB  - OBJECTIVE: To evaluate whether intramedullary tumor of the cervical spinal cord
      is amenable to aggressive surgery and to clarify surgical timing and important
      points for tumor removal. PATIENTS AND METHODS: Fifty-eight patients with
      intramedullary tumor of the cervical spinal cord were examined by magnetic
      resonance imaging and treated by microsurgery in Huashan Hospital between May
      1988 and December 1994. The results were analysed by F or Chi square tests.
      RESULTS: Tumors were totally resected in 50 cases (86.2%), subtotally resected in
      7 and partially resected in 1. Forty-five (77.6%) patients had their neurological
      status improved postoperatively. Most patients with moderate neurological deficit
      can recover remarkably after total tumor removal. Laser surgery is especially
      helpful for treating lipoma. CONCLUSIONS: Intramedullary tumor of the cervical
      spinal cord is amenable to total tumor removal. Operation is suitable when a
      patient presents moderate neurological deficit. Proficient surgical technique and
      standards for total tumor resection are essential for good results. Preoperative
      radiotherapy contributes to difficult surgery and poor prognosis, and is not
      recommended.

PMID- 9275352
TI  - A dose related response of 6-OHDA on chicken spectral sensitivity and oscillatory
      potentials of recording electroretinograms.
AB  - OBJECTIVE: To further study the contribution of dopamine system to the local
      growth controlling mechanisms, a dose related response of 6-hydroxydopamine (6
      OHDA) was studied by recording electroretinograms (ERGs). METHODS: The spectral
      sensitivity of the b-waves and spectral efficiency function of oscillatory
      potentials (OPs) including OP1, OP2 and OP3 in 4 different doses group were
      measured. The effect of ascorbate that must be contained in solution of 6-OHDA
      was first tested with the spectral sensitivity of the b-waves and a correlation
      between response of the OPs and age, as well as a difference in both own eyes was
      analyzed for determining an intra-subject and inter-subject variance. RESULTS: An
      enhanced response was found in OP1, OP2 with doses of 175 micrograms and OP3 with
      dose of 150 micrograms, and the effect of OPs was mainly in wavelength from 620
      nm to 480 nm. No significant increase was found in the spectral sensitivity of
      the b-waves. The dose 200 micrograms seemed to be toxic to the retina estimated
      by both spectral sensitivity of the b-waves and spectral efficiency function of
      the OPs. CONCLUSIONS: The dose 175 micrograms and 150 micrograms of 6-OHDA
      yielded an effect on the chicken retina.

PMID- 9275353
TI  - Quantitative research for improving respiratory muscle contraction by breathing
      exercise.
AB  - OBJECTIVE: To investigate the effects of breathing exercise on chronic
      obstructive pulmonary disease (COPD). PATIENTS AND METHODS: 324 patients stable
      COPD were randomly assigned to either the breathing exercise group (Group I) or
      control group consisting of placebo (Group II). The maximum respiratory pressure
      (320 cases) and transdiaphragmatic pressure (129 cases) were monitored via RMS-I
      and Type-2 pressure measurements. The breathing exercises were taught and checked
      by experienced specialists periodically. Comparison was made between Group I and
      Group II using maximum inspiratory pressure (MIP), maximum expiratory pressure
      (MEP), diaphragmatic pressure (Pdi) and maximum transdiaphragmatic pressure
      (Pdimax) after 1 to 20 months. RESULTS: In Group I MIP increased by 30.42%, MEP
      32.10%, Pdi 30.94% and Pdimax 65.59% (P < 0.001). No significant changes were
      observed in Group II given the placebo. The MIP, MEP, Pdi and Pdimax were 6.95%,
      2.92%, 14.63 and 9.05% respectively (P > 0.05). CONCLUSIONS: Breathing exercise
      has a potent and long lasting effect on respiratory muscle contraction. The
      methods mentioned above can be used as standard quantitative index for
      contractile properties of respiratory muscle.

PMID- 9275354
TI  - Changes of distribution of platelet activating factor in the lung of rats with
      hypoxic pulmonary hypertension.
AB  - OBJECTIVE: To investigate the role of platelet activating factor (PAF) in the
      hypoxic pulmonary hypertension. MATERIAL AND METHODS: Fifteen of 30 male Wistar
      rats were exposed to hypoxia for 3 weeks, and another 15 rats served as controls.
      The pulmonary arterial pressure was examined by catheterization. The sections of
      rat lung were treated by the avidin-biotin-peroxidase complex method to expose
      the location of PAF. RESULTS: The rats developed pulmonary hypertension and right
      ventricular hypertrophy after hypoxic exposure. Under the light microscope, PAF
      is distributed on the vascular and alveolar walls of normal lung, and the content
      of PAF in the lung of rats with hypoxic pulmonary hypertension are remarkably
      higher than those of normoxic controls. CONCLUSIONS: PAF plays not only a
      physiological role in the rat lung, but also a pathophysiologic role in hypoxic
      pulmonary hypertension.

PMID- 9275356
TI  - Alterations of level of total genomic DNA methylation and pattern of c-myc, c-Ha
      ras oncogene methylation in human gastric carcinogenesis.
AB  - OBJECTIVE: To investigate the status of DNA methylation in gastric
      carcinogenesis. METHODS: We analysed methylation pattern of c-myc, c-Ha-ras
      oncogenes by southern blot hybridization. DNA from cancerous, paracancerous and
      non-cancerous area of surgically resected samples in 21 cases of advanced gastric
      cancer were digested with MspI/HpaII and hybridized with the two genomic 32P
      labelled probes. In addition, the level of total genomic DNA methylation was
      measured by incubating DNA with 3H-S-Adenosylmethionine (3H-SAM) in the presence
      of a methylase which methylates all the cytosine residues that are in the double
      CpG (cytosine-guanine). RESULTS: The results indicated that both c-myc and c-Ha
      ras oncogene fragments containing CCGG sequence were hypomethylated in DNA
      samples from cancerous (10/21 and 5/10) and paracancerous (13/21 and 4/10) areas.
      Moreover, the level of total genomic DNA methylation in cancerous tissue was
      significantly lower than that in non-cancerous and paracancerous mucosa tissues
      (P < 0.05). The results from two methods are incompletely alike. CONCLUSION:
      These results supported a strong correlation between DNA hypomethylation and
      gastric carcinogenesis, particularly methylated pattern of c-myc and c-Ha-ras
      oncogenes fragments containing CCGG sequence was abnormal in gastric mucosa
      tissue from gastric cancerous and paracancerous areas.

PMID- 9275355
TI  - Effect of probucol on mRNA expression of glomerular antioxidant enzymes in rat
      with subtotal nephrectomy.
AB  - OBJECTIVE: To investigate 1) the glomerular mRNA expression and protein activity
      of antioxidant enzymes (AOEs) including superoxide dismutase (SOD) and glutathine
      peroxidase (GSH-Px) and the glomerular content of lipid peroxide-malondiadehyde
      (MDA), 2) the effects of probucol (P), a potent antioxidant agent on these AOEs
      and MDA levels, in the chronic phase of subtotal nephrectomized rats. METHODS:
      The adult male Spregue-Dawley rats were randomly divided into three groups at the
      first week after subtotal renal ablation. Group 1 was sham rats (sham n = 8),
      group 2 underwent 5/6 nephrectomy without special therapy (5/6 Nx n = 8), and
      group 3 with 5/6 nephrectomy received probucol (5/6 Nxs+P n = 8) at a dose of 1%
      in the rat chow. At the 12th week after P was administrated, all of the rats were
      sacrificed to remove left kidney for the determination of glomerular level of
      MDA, activity of SOD, and GSH-Px, glomerular mRNA expression of AOEs by Northern
      blot analysis as well as a histological examination. RESULTS: In 5/6 Nx, serum
      cholesterol, proteinuria increased and creatinine clearance decreased
      progressively with age as compared with that in sham. Those abnormalities as well
      as glomerulosclerosis index (GI) ameliorated with the administration of probucol
      at the 12th week after subtotal nephrectomy [GI: sham 3.12 +/- 1.20, P < 0.01 vs
      5/6 Nx 5/6 Nx 188.6 +/- 25.1; 5/6 Nx +/- P, 106.9 +/- 17.6, P < 0.05 vs 5/6 Nx].
      The probucol therapy also significantly improved the decrease of glomerular Mn
      SOD and GSH-Px both at mRNA level and protein activity and the increase of
      glomerular MDA content. CONCLUSIONS: We demonstrated a deficiency of glomerular
      AOEs in the chronic phase of remnant kidney, which may contribute to the
      progression of renal injury. The protective effects of probucol on both renal
      functional impairment and the development of glomerulosclerosis may be partially
      associated with improving surviving glomerular AOEs.

PMID- 9275357
TI  - Detoxicating enzymes of Entamoeba histolytica and their detoxifying roles.
AB  - OBJECTIVE: To investigate the Entamoeba histolytica living in the low oxygen
      concentration colon of the host and how does it survive in the circumstance after
      invading the tissues with high oxygen concentration while obtaining oxygen
      without being damaged by the toxins. MATERIAL AND METHODS: E. histolytica
      cultured for 48 hours was collected, centrifuged, rinsed, ultrasonically
      shattered and again centrifuged, and the activities of superoxide dismutase and
      the catalase in the supernatant were determined. The catalase and peroxidase were
      identified by the electron microscopic enzyme cytochemical reaction technique.
      RESULTS: E. histolytica contained 122.42 +/- 15.47 U/mgpr of superoxide
      dismutase, 126.05 +/- 17.04 K/mgpr of catalase and peroxidase, and all of them
      are detoxifying enzymes. Catalase and peroxidase were located within microsomes
      and lysosome-like organelles respectively. CONCLUSIONS: E. histolytica contains
      the detoxifying enzymes as superoxide dismutase, catalase and peroxidase, that
      may prevent the aerobic metabolism from being poisoned by the activated oxygen
      free radical (superoxide anion radical and hydrogen peroxide) produced in this
      process, suggesting that the detoxifying function of these enzymes play an
      important defensive role in the survival of E. histolytica.

PMID- 9275358
TI  - Colchicine reduces hepatic fibrosis in mice infected with Schistosoma japonicum.
AB  - OBJECTIVE: Colchicine has been used clinically to treat hepatic cirrhosis caused
      by multiple etiologies. MATERIALS AND METHODS: The effect of colchicine on the
      liver fibrosis of mice infected with Schistosoma japonicum were studied. The
      morphological observation and morphometric analysis of the infected and
      untreated, and infected and treated groups were proceeded under the light
      microscopy, and morphological observation was made under electron microscopy.
      RESULTS: The results of morphometriic analysis in histological sections showed
      that the collagen fibers area per schistosome's egg was decreased in the infected
      and treated groups 10 to 13 weeks after infection. The decrease in the group of
      13 weeks was significant statistically. The egg numerical density on area
      increased continuously from 10 to 13 weeks in both untreated and treated groups
      in similar degree. The ultrastructural study showed the accumulation of collagen
      fibrils around the hepatocytes and in the space of Disse decrease and
      ultrastructural lesion of hepatocytes get recovery in the treated group.
      CONCLUSIONS: These findings suggest that colchicine has therapeutic effect on
      schistosomal liver fibrosis, through not only killing off the schistosome but
      interfering the metabolism of collagen.

PMID- 9275360
TI  - Evaluation of glucose metabolic disorder: insulin resistance and insulin
      receptors in critically ill children.
AB  - OBJECTIVE: To explore the pathogenesis of glucose metabolic disorder and insulin
      resistance in critically ill children under severe stress. METHODS: To test
      glucose, lactate, glucagon, insulin, c-peptide, cortisol levels in 50 critically
      ill children. While we measured 125I-insulin binding to erythrocytes of 13
      critically ill children who had hyperglycemia and hyperinsulinemia. Glucose and
      lactate were measured biochemically. Insulin, c-peptide, cortisol and glucagon
      were determined by RIA. Erythrocytes insulin receptor was detected by insulin
      radioreceptor assay. RESULTS: Glucose, lactate, insulin, c-peptide, glucagon,
      cortisol, insulin/glucose, insulin/glucagon ratio in patients were higher than
      those in normal controls (P < 0.05). As compared with normal controls, the
      maximum 125I-insulin bound and insulin receptor number per cell were
      significantly lower (P < 0.01). But there was no difference of mean value in
      receptor affinity (P > 0.05). CONCLUSIONS: Hyperglycemia is common in critically
      ill children during stress, which may be attributed to hormones disturbance and
      tissure insulin resistance. Insulin receptor defect due to comprehensive factors
      was one of the important causes for insulin resistance. The blood glucose level
      can be used as an predicting index in ICU.

PMID- 9275359
TI  - An epidemiological survey on use and abuse of antianxiety drugs among Beijing
      residents.
AB  - OBJECTIVE: To investigate the current trend of use and abuse of antianxiety drugs
      in Beijing residents in 4 urban and 2 rural areas. METHODS: A cluster sampling
      household survey of 6567 subjects out of 3000 families was made by 6 local grass
      roots mental health centers collaboratively. Screened with designed
      questionnaire, the positive addicted subjects were examined with present state
      examination (PSE), eysenck personality questionnaire (EPQ) and social disability
      screening schedule (SDSS) to detect their psychosocial status. RESULTS:
      Benzodiazepine (BZD) has been widely prescribed and the rate of usage for 1 year
      is 61.82/1000, whereas the rate of dependence is 16.29/1000, constituting 1/4 of
      long-term users. This study also indicates that Valium is a most preferred drug
      among all available BZD used by the majority of addicted subjects. CONCLUSIONS:
      It is concluded that the reported dependence is not epidemic but iatrogenic in
      nature attributable to persistent misuse of BZD. It is stressed that guideline of
      rational clinical application of BZD should be laid down so as to markedly reduce
      further possible misuse and abuse of the drugs of this kind.

PMID- 9275361
TI  - A small depressed early cancer of the second portion of duodenum: report of a
      case and review of Japanese literature.

PMID- 9275362
TI  - Estrogen and progestin cytosol receptor concentrations in patients with
      endometriosis and their changes after gossypol therapy.

PMID- 9275363
TI  - Effects of nicotinamide on prevention and treatment of streptozotocin-induced
      diabetes mellitus in rats.
AB  - OBJECTIVE: To study the effect of nicotinamide (NAA) on prevention and treatment
      of STZ-induced diabetes mellitus in rats. MATERIAL AND METHODS: 30 Sprague-Dawley
      rats were randomly divided inot three groups: 20 rats were given NAA 1 g/kg/day
      intramuscularly (10 rats) or orally (10 rats) as experimental groups and the
      other 10 rats by normal saline orally as control group. Three days later, all 30
      rats received streptozotocin (STZ) 55 mg/kg by intraperitioneal injection and
      took NAA or normal saline continuously as described above for 14 days. During the
      study, fasting blood glucose (FBG) was measured before and 72 hours after STZ
      injection and every 2-3 days later on with Glucometer, 24 hours urinary glucose
      excretion (UGE) was determined once every 4 days with glucose oxidase, body
      weight was determined every week, the volume of 24-hour water intake and urine
      excretion were determined twice and once a week respectively. RESULTS: Two weeks
      after STZ injection, FBG and 24 hours UGE of all rats taking NAA were normal or
      nearly normal, islet function and morphology revealed no significant differences
      compared with those of the normal, whereas all rats of control group remained
      hyperglycemic (> 16.6 mmol/L) and markedly higher 24 hours UGE as compared with
      the normal islets appeared atrophic with decrement of B cell population.
      CONCLUSIONS: The results showed that NAA may effectively prevent the occurrence
      of STZ-induced diabetes mellitus in rats, suggesting that NAA may be an effective
      agent for prevention and treatment of insulin-dependent diabetes mellitus (IDDM)
      in prediabetic and early stage of IDDM.

PMID- 9275364
TI  - Plasma endothelin and atrial natriuretic peptide in normal and hypertensive
      pregnancy.
AB  - OBJECTIVE: To investigate the possible role of endothelin-1 (ET-1) and atrial
      natriuretic peptide (ANP) in the pathogenesis of pregnancy-induced hypertension
      (PIH). MATERIAL AND METHODS: A total of 110 normal pregnant women (in three
      trimesters, labour or postpartum) and 30 patients with PIH were studied by
      measuring plasma ET-1 and ANP levels by radioimmunoassay; 23 normal non-pregnant
      women were selected as controls. RESULTS: Compared with normal non-pregnant
      women, plasma ET-1 levels were significantly decreased in normal pregnant women
      during all three trimesters. Plasma ET-1 level was significantly increased in the
      2nd stage of labour, compared with that in the 3rd trimester. There were
      significant positive correlation between plasma ET-1 level and mean arterial
      pressure in normal non-pregnant women and normal pregnant women in all three
      trimesters. Compared with matched normal pregnant women, plasma ET-1 and ANP
      levels were significantly increased, while plasma ANP/ET-1 ratio was
      significantly decreased in PIH patients. Significant positive correlations
      existed between plasma ET-1 level and mean arterial pressure or the score index
      of the severity of PIH. After the treatment with magnesium sulfate infusion,
      plasma ET-1 and ANP levels were significantly decreased, but plasma ANP/ET-1
      ratio was significantly increased in PIH patients. CONCLUSIONS: Augmentation of
      ET-1 secretion and attenuation of ANP function may be responsible for the
      development of PIH. ET-1 secretion may be indirectly influenced by magnesium in
      PIH.

PMID- 9275365
TI  - Recombinant human granulocyte colony-stimulating factor after allogeneic bone
      marrow transplantation.
AB  - OBJECTIVE: To examine the effect of rhG-CSF on allogeneic bone marrow
      transplantation. PATIENTS AND METHODS: One hundred and twenty patients with acute
      or chronic leukemia received HLA-A.B.DR identical and MLC negative sibling donor
      allo-BMT. Among them, 58 cases of were treated with recombinant human granulocyte
      colony-stimulating factor (rhG-CSF), while the other 62 cases of the 120 patients
      were treated as control. RESULTS: Clinical results showed that the time taken to
      reach an absolute neutrophil count > 0.5 x 10(9)/L was significantly faster in
      patients who received rhG-CSF compared with control patients (16.24 +/- 0.25 vs
      25.20 +/- 0.16 days. P < 0.001), with significantly less early fever days in
      patients received rhG-CSF (1.17 +/- 1.10 vs 4.01 +/- 0.37 P < 0.001). We did not
      observe any increase in acute GVHD and relapse in myeloid leukemia patients. But
      7 of 16 patients with ALL relapsed after allo-BMT in rhG-CSF group, while only 3
      of 11 patients with ALL relapsed after allo-BMT in control grant (P > 0.05). This
      phenomenon has not been reported up to now. CONCLUSIONS: rhG-CSF can promote
      engraftment and reduce early fever days after BMT. rhG-CSF has not any effect on
      a GVHD. The effect of rhG-CSF on leukemia relapse needs to be further studied.

PMID- 9275366
TI  - Implantation of autologous skin fibroblast genetically modified to secrete
      clotting factor IX partially corrects the hemorrhagic tendencies in two
      hemophilia B patients.
AB  - OBJECTIVE: To examine the safety and effects of gene therapy for hemophilia B by
      implantation of autologous fibroblasts genetically modified to secrete clotting
      factor IX (hFIX). PATIENTS AND METHODS: Two hemophilia B patients LD and LW were
      selected from one family to accept gene transfer study. The hFIX protein of both
      patients were about 100 ng/ml plasma and hFIX activity was about 2%. The
      autologous skin fibroblasts of the two patients were genetically modified by
      retrovirus-mediated gene transfer with XL-IX and N2CMVIX vector (HBSF-IX). Human
      hFIX protein was measured by ELISA, hFIX activity was measured by one-stage
      clotting assay and barium citrate sorbent method. hFIX inhibitor was assayed by
      Bethesda methods. Human hFIX cDNA was detected by PCR. HBSF-IX cells were mixed
      with collagen for injection after safety assessments. RESULTS: The HBSF-IX cells
      from the two patients secreted hFIX at high levels in vitro. After implantation
      of autologous HBSF-IX cells, no treatment-related side effects were observed.
      Plasma hFIX protein in both patients increased over 2 folds after several
      injections of HBSF-IX cells and persisted for more than 420 days. Blood clotting
      activity increased significantly in both patients, hemorrhagic tendencies have
      been partially corrected after treatment. Further elevation of hFIX can be
      achieved by repeating the same treatment 420 days later in Patient LD.
      CONCLUSIONS: Implantation of autologous fibroblast genetically modified to
      secrete human hFIX offers a simple, safe and effective approach to gene therapy
      of hemophilia B.

PMID- 9275367
TI  - Measurements of membrane diffusing capacity and pulmonary capillary blood volume
      in normal subjects and patients with mild emphysema.
AB  - OBJECTIVE: To establish predicted values of membrane diffusing capacity (Dm) and
      pulmonary capacity blood volume (Vc), to compare the predicted values from our
      equations with those for Caucasians, to determine whether there are changes
      initially in Dm or Vc in patients with mild emphysema. PATIENTS AND METHODS:
      Diffusing capacity for carbon monoxide (DLco), Dm and Vc were determined in 86
      normal subjects and 16 patients using the single-breath diffusing capacity for
      carbon monoxide (DLcosB) with two different alveolar concentrations of oxygen.
      RESULTS: The predicted equations are as follows. For males, DLco (ml/min/mm Hg) =
      0.37H-0.19A-27.8; Dm (ml/min/mm Hg) = 0.65H-0.24A-53.7; Vc(ml) = 0.88H-78.9. For
      females, DLco = 0.28H-22.7; Dm = 0.59H-53.6; Vc = 66.6-0.36A. DLco and Vc are
      lower in Chinese than Caucasians while Dm is similar in Chinese and Caucasians.
      Eleven of 16 patients had a low DLco (< 80% predicted value), 12 had a low Dm and
      5 had a low Vc. Eight of 12 patients with a low Dm also had a low DLco, but in 4
      the DLco was normal. Nine of 12 with low Dm had a normal Vc. CONCLUSIONS: This
      study provides prediction equations of Dm and Vc. Chinese have a low DLco because
      their Vc is lower than Caucasians. The DLco and Dm are abnormal in a comparable
      percentage of patients. In patients with mild emphysema, the Dm becomes abnormal
      before the Vc.

PMID- 9275368
TI  - Studies on prophylactic effect of artesunate on schistosomiasis japonica.
AB  - OBJECTIVE: To examine the prophylactic effect of artesunate on schistosomiasis
      japonica by killing schistosomula. METHODS: Mice, rabbits and dogs after
      infection with cercariae of schistosoma japonicum (S. japonicum) were treated
      with artesunate on the 7th day at a dose of 300 mg/kg, 20-40 mg/kg and 30 mg/kg
      respectively once a week for 4-6 weeks. A double-blind test was used. A total of
      864 persons in highly endemic areas for schistosomiasis were administered either
      artesunate at a dose of 6 mg/kg once a week for 8 weeks or identical placebo with
      the same dose-schedule during transmission season for S. japonicum. Four weeks
      after the last dosing, fecal examinations for S. japonicum eggs and miracidia
      were carried out to evaluate the prophylactic effect. RESULTS: Worm reduction
      rates in mice, rabbits and dogs were 77.50-90.66%, 99.53% and 97.10%
      respectively. All of the 467 residents in 2 trials were free from eggs or
      miracidia upon stool examinations whereas in the control groups with placebo, 15
      out of 218 (6.9%) and 26 out of 179 (14.5%) were stool eggs and/or miracidia
      positive in the first and second trial, respectively. Side effects were mild. No
      significant changes in routine blood and urine tests, electrocardiogram, hepatic
      and renal functions were observed after artesunate administration. CONCLUSIONS:
      Animal experiments and field trials have demonstrated good efficacy of artesunate
      on killing schistosomula with little side effects. Thus, the drug is suggested to
      be used on the population in endemic areas for prevention of schistosomiasis.

PMID- 9275369
TI  - Different susceptibility of cervical keratinocytes containing human
      papillomavirus to cell-mediated cytotoxicity.
AB  - OBJECTIVE: To detect the factors responsible for the susceptibility of cervical
      keratinocytes infected with human papillomavirus (HPV) to non-specific lysis
      mediated by natural killer (NK) and lymphokine activated killer (LAK) cells.
      MATERIALS AND METHODS: Five cervical keratinocyte lines: CaSki, SiHa, HeLa
      (representing high grade squamous intraepithelial lesion (HSIL) ), W12
      (representing low grade squamous intraepithelial lesion (LSIL) ) and NCx, (normal
      cervix) were used as target cells in the four-hour lactate dehydrogenase (LDH)
      release cytotoxicity assay. The effector cells were NK and LAK. The modulatory
      effects of interferon gamma (IFN gamma) and tumor necrosis factor alpha (TNF
      alpha) pretreatment of keratinocytes were investigated by adding IFN gamma or TNF
      alpha into the flasks of target cells 48 hours before the cytotoxicity assays.
      The blocking effects of anti-intercellular adhesion molecule-1 (ICAM-1) and anti
      lymphocyte function-associated antigen-1 (LFA-1) monoclonal antibodies (Mabs)
      were also studied. RESULTS: All the 5 cervical keratinocytes were susceptible to
      LAK, but not to NK. The sensitivity varied among the cell lines. LAK had better
      killing effects on HSIL than on LSIL. Pretreatment of target cells with IFN gamma
      and TNF alpha increased the killing mediated by LAK, but had little effect on NK
      activity. Anti-ICAM-1 and anti-LFA-1 Mabs inhibited LAK-mediated cytotoxicity.
      CONCLUSIONS: All the HPV infected keratinocytes used in the experiments are NK
      resistant and LAK-sensitive cells. IL-2, IFN gamma and TNF alpha play some
      critical roles in the regulation of the susceptibility of cervical keratinocytes,
      especially HSIL to LAK-mediated cytotoxicity in vitro.

PMID- 9275370
TI  - Glucokinase gene variants in Chinese subjects with the common form of NIDDM.
AB  - OBJECTIVE: To determine whether mutation of the coding or junction region of
      glucokinase gene (GCK) is also the pathogenic cause of the common form of non
      insulin-dependent diabetes mellitus (NIDDM) in Chinese. METHODS: Single strand
      conformation polymorphism (SSCP) analysis was performed after the 12 exons and
      junction regions of GCK of each subject studied were separately amplified with
      polymerase chain reaction (PCR). The molecular scanning was carried out in 30
      Chinese subjects with common form NIDDM having the age of onset at or before 45
      years, and/or with positive family history of diabetes mellitus (NIDDM-A group).
      Further screening of the mutation/variation found was conducted in 56 NIDDM
      subjects (NIDDM-B group) and 134 non-diabetes subjects (ND group) in order to
      define their frequencies. RESULTS: No mutation was found by molecular scanning in
      coding or junction region of GCK in NIDDM-A group. A variant of intron I b was
      detected in GCK of NIDDM subjects, especially in those with early age of onset
      and/or with positive family history of diabetes. Significant difference in
      incidences was found between ND group and NIDDM-A+B group (0% vs 4.7%, Fisher
      exact P = 0.022). CONCLUSIONS: (1) Mutation of coding and junction regions of GCK
      is not the main pathogenic factor of common form NIDDM in Chinese subjects. (2) A
      variant of GCK intron I b may be found in NIDDM in Chinese, especially in those
      with early age of onset and/or with positive family history of diabetes. Its role
      in the expression of GCK remain to be elucidated.

PMID- 9275371
TI  - Role of intracardiac angiotensin II in cardiac dysfunction of rat during septic
      shock.
AB  - OBJECTIVE: To observe changes in the content of myocardial angiotensin II and its
      role in cardiac dysfunction of rat during septic shock. METHODS: Septic shock
      model was produced by cecal ligation and puncture (CLP) operation on rats.
      Experimental rats were given captopril 15 mg.kg-1/d per os for 3 days before CLP
      operation. Mean blood pressure and left ventricular pressure were recorded.
      Myocardial angiotensin converting enzyme (ACE) activities were determined by a
      fluorometric assay and myocardial angiotensin II content was measured by
      radioimmunoassay. Highly purified membrane of sarcoplasmic reticulum (SR) was
      prepared from rat hearts. Assays were made of ATP-dependent Ca2+ uptake by
      cardiac SR and (3H) ryanodine binding to SR. RESULTS: Myocardial angiotensin II
      content increased by 51.5% (P < 0.01) at the 18th hour post CLP, meanwhile there
      was a decrease in left ventricular +/- dp/dtmax value and the impairment in Ca2+
      uptake and (3H) ryanodine binding to cardiac SR. Preliminary administration of
      captopril reduced myocardial ACE activity and angiotensin II content, but
      increased left ventricular +/- dp/dtmax value. In comparison to shock group, the
      initial rate and the capacity of SR Ca2+ uptake were increased by 120% (P < 0.01)
      and 33.9% (P < 0.05), the Bmax value of (3H) ryanodine binding to SR was also
      elevated, while the Kd value remained unchanged. CONCLUSIONS: The elevated
      intracardiac angiotensin II, resulting from the activation of myocardial ACE
      during sepsis, probably serves as one of the important mediators participating in
      the pathogenesis of heart failure: the effects of angiotensin II may be
      associated with the disturbance of Ca2+ transport function of cardiac SR.

PMID- 9275372
TI  - Effect of extended parietal cell vagotomy on long-term nutrition and digestive
      function.
AB  - OBJECTIVE: To study the effect of extended parietal cell vagotomy (EPCV) on long
      term nutritional status and digestive-absorption function. PATIENTS AND METHODS:
      Thirty-six patients undergoing EPCV were compared with 30 patients with subtotal
      gastrectomy (SG) 7-14 years after operation. The patients were evaluated in terms
      of nutritional status, gastric secretion, gastrointestinal motility, and
      intestinal digestive-absorption function. RESULTS: The nutritional status was
      generally less satisfactory in 33.3% patients with anemia after SG and body
      weight decreased in 54%. The patients after EPCV were all in good nutritional
      status, and had no symptoms of anemia; 56% of them had body weight increased by
      more than 3 kg. The mean basal acid output (BAO), maximal acid output (MAO), and
      peak acid output (PAO) of the EPCV group were significantly reduced after
      operation (P < 0.01), and moderately reduced as compared with those of the
      control group (P > 0.05). But the BAO, MAO, and PAO of the SG group were more
      markedly reduced than those of the control group (P < 0.001) before operation.
      Vitamin B12, folacin, intrinsic factor and iron protein level of serum in the
      EPCV group were slightly decreased as compared with those of the control group (P
      > 0.05), but more significantly decreased in the SG group than in the control
      group (P < 0.001). Iron protein and intrinsic factor level was lower than the
      normal level. The gastric emptying time and small intestinal passthrough time of
      EPCV were more close to the normal physiological status, but in the SG group,
      they were significantly fast (P < 0.001). The results of intestinal D-xylose
      absorption test in EPCV and SG groups were similar (P > 0.05). CONCLUSIONS: EPCV
      is capable of preserving gastric acid of physiologic level and normal digestion
      absorption function. The effect of EPCV on long-term nutrition and digestion
      absorption function was extremely milder than that of SG. Therefore, a
      theoretical basis is provided for the rationality of EPCV.

PMID- 9275373
TI  - Structural alterations of resistance vessels of spontaneously hypertensive rats
      and protective effects of captopril.
AB  - OBJECTIVE: To observe the structural alterations of resistance vessels in
      spontaneously hypertensive rats (SHRs) and to evaluate the effects of captopril
      on them. METHODS: 15-week-old male SHRs were treated with oral captopril (100
      mg/kg/day) for 12 weeks. Age- and sex-matched SHRs and Wistar-Kyoto rats (WKY)
      were fed under the same conditions without captopril administration for the same
      duration. All rats were killed at the age of 27 weeks. The structural parameters
      included media width, lumen diameter, media-lumen ratio, vascular collagen area
      (VCA) and vascular collagen density (VCD). The media width, lumen diameter and
      media-lumen ratio were measured in hhematoxylin and eosin staining sections under
      a direct light microscope and VCA and VCD in picrosirius red staining sections
      under a polarizing light microscope. All the values were processed with a
      computer image analyzer. RESULTS: There were thicker media width, smaller lumen
      diameter, higher media-lumen ratio and larger VCA in untreated SHRs than in WKY.
      Captopril inhibited media thickening, with lumen diameter decreasing, media-lumen
      ratio increasing and VCA enlarging. There was no significant difference in VCD
      among the three groups. CONCLUSIONS: Adverse structural alterations occur in
      resistance vessels of SHRs and captopril may prevent their progression.

PMID- 9275374
TI  - An investigation of adult outcome of hyperactive children in Shanghai.
AB  - OBJECTIVE: To evaluate the outcome of hyperactive children diagnosed 15 years ago
      at the average age of 25. PATIENTS AND METHODS: Conditions of 197 children who
      were diagnosed as having minimal brain dysfunction (MBD) in 1979-1980 at our
      center and 103 normal controls were assessed by the parents in an inquiry form
      including educational achievement, occupational rank, persistence of attention
      deficit hyperactive disorder (ADHD) (MBD) symptoms, and pervasive conduct
      problems after a 15-year follow-up. RESULTS: Compared with normal controls, the
      probands continued to reveal typical symptoms in 70% of these children, completed
      less formal schooling, and were less often employed in higher-level professions,
      but did not exhibit significantly more conduct problems. CONCLUSIONS: Only about
      30% of the formerly hyperactive children can get out of the shadow of ADHD (MBD)
      and succeed in their academic or occupational performance, and the rest continue
      to reveal some symptoms and some problems in their adult life.

PMID- 9275375
TI  - Effects of ginkgolide B on isobaric hypoxic pulmonary hypertension in rats.
AB  - OBJECTIVE: To evaluate the effects of Ginkgolide B, a specific platelet
      activating factor (PAF) antagonist, on hypoxia-induced pulmonary hypertension and
      pulmonary vascular remodeling. MATERIALS AND METHODS: Forty male Wistar rats were
      divided into 4 groups, receiving normal saline, Ginkgolide B, isobaric hypoxia
      and isobaric hypoxia plus Ginkgolide B respectively. Pulmonary hemodynamics were
      assessed via right heart catheterization. Pulmonary vascular remodeling were
      examined by a computerized image analyser. RESULTS: Chronic hypoxia (FiO2 = 0.10,
      3 weeks) caused pulmonary hypertension, pulmonary vascular remodeling and right
      ventricular hypertrophy in rats. Treatment with Ginkgolide B reduced the extent
      of pulmonary hypertension, pulmonary vascular remodeling and right ventricular
      hypertrophy induced by hypoxic exposure. CONCLUSIONS: The results suggest that
      PAF participates in the process of chronic hypoxic pulmonary hypertension and
      pulmonary vascular remodeling, and PAF antagonist could be a potentially useful
      agent for preventing hypoxic pulmonary hypertension.

PMID- 9275376
TI  - Relationship between some humoral factors and left ventricular hypertrophy in
      essential hypertension.
AB  - OBJECTIVE: To evaluate the relationship between certain humoral factors and left
      ventricular hypertrophy (LVH) in essential hypertension. PATIENTS AND METHODS: 62
      essential hypertension (EH) patients (32 men, 30 women; mean age, 55 years) and
      20 normotensive healthy subjects (10 men, 10 women: mean age, 52 years) were
      studied. EH patients were divided into LVH group and non-LVH group by
      echocardiography. After an overnight fast, blood samples were taken for the
      determination of parathyroid hormone (PTH), angiotensin II (ATII) and aldosterone
      (ALD) by radioimmunoassay. RESULTS: There was a significant difference in PTH. AT
      II and ALD between the EH group and control group. Furthermore, in LVH group PTH,
      ATII and ALD elevated significantly as compared with non-LVH group. In addition,
      we found that LVMI (left ventricular mass index) correlated with ATII (r = 0.342,
      P < 0.01) and ALD (r = 0.356, P < 0.01). There was a more significant correlation
      between LVMI and PTH (r = 0.422, P < 0.0025). CONCLUSIONS: Some humoral factors
      are important determinants of LV mass. Besides the reninangiotensin-aldosterone
      system, PTH might play an important role in cardiac hypertrophy.

PMID- 9275377
TI  - Orthognathic surgery in China: past, present and future.

PMID- 9275378
TI  - Long-term results of intravesical N-CWS therapy for preventing bladder cancer
      recurrence after operation.

PMID- 9275379
TI  - Update on biliary stent occlusion.

PMID- 9275381
TI  - [Effects of smoking on lung function in populations of Beijing and Guangzhou].
AB  - OBJECTIVE: To analyse the relationship between cigarette smoking and lung
      function in populations of Beijing and Guangzhou. METHODS: Complete lung function
      and smoking habit data were recruited from 7983 men and women aged 35-59 in or
      around Beijing and Guangzhou. Comparisons were made between smokers and never
      smokers. RESULTS: The mean values of FEV1/H2, FEF/H2 and FEV1/FVC are all lower
      in smokers than in never smokers for male smokers, the observed mean value of
      FEV1/H2 for each age group in smaller than the respective predicted value, and
      its descending trend with aging is more obvious than the predicted value when re
      examination after 2-4 years; furthermore, smokers had higher prevalences of
      respiratory symptom and COPD. CONCLUSION: Cigarette smoking is harmful to lung
      function.

PMID- 9275380
TI  - [A sample survey and multiple factor analysis on asthma in urban area of
      Shanghai].
AB  - OBJECTIVE: To estimate the prevalence of asthma in urban residents of Shanghai in
      1990 and evaluate the risk factors of asthma. METHODS: A cluster uneven random
      survey of asthma was conducted among 36,872 urban residents, 5/1000 of the
      population of the city. The asthmatics were suspected based upon case history,
      and then confirmed by home visit and further investigation. Single factor and
      unconditional logistic regression analysis were employed to evaluate the risk
      factors of asthma. RESULTS: The accumulative prevalence of asthma was 1.53% for
      age group 0-35 and it was higher in male (1.74%) than in female (1.31%). Sex, age
      and type of living house were possible risk factors. The prevalences were much
      higher among people with history of TB and pneumonia of which the values of
      relative risks were 2.53 and 4.95, respectively. Histories of food, drug and
      other kinds of hypersensitivity were significantly related to the history of
      asthma. CONCLUSION: Several risk factors possibly associated with asthma were
      identified in Shanghai area.

PMID- 9275382
TI  - [Comparative observation on the relationship between the MEFV and the visual
      inspection of small airway].
AB  - OBJECTIVE: To compare the relationship between the MEFV and the visual inspection
      of small airway. METHODS: According to the result on small airway function test
      (MEFV), the patients were divided into two group: MEFV abnormal group and MEFV
      normal group. Their bronchus and peripheral airway were observed with
      bronchofiberscope and ultra-thin bronchofiberscope. The visual appearance of the
      airways was scored in the light of the presence or absence of erythema, edema,
      secretions, etc. RESULTS: The score of visual appearance observed or bronchitis
      index (BI) in small airway was 7.7 +/- 0.8 (BI: 3.0 +/- 0.8) and 4.7 +/- 1.6 (BI:
      1.5 +/- 0.5) respectively in MEFV abnormal group and in MEFV normal group, namely
      the score in MEFV abnormal group was significantly higher than that of normal
      group (P < 0.01). The degree of pathological change in small airway was
      significantly correlated with the results of V25, V50, r = -0.6271, (P < 0.05)
      and r = 0.6964, (P < 0.02). CONCLUSION: The abnormal of MEFV may reflect
      inflamative pathological changes of small airway.

PMID- 9275383
TI  - [A study on the mechanism of severe hypoxemia associated with acute unilateral
      atelectasis in dogs].
AB  - OBJECTIVE: To study the mechanism of severe hypoxemia associated with acute
      unilateral atelectasis (AUA). METHODS: Six dogs with acute left side atelectasis
      were studied during the period of rest and exercise. The pulmonary shunt and PaO2
      were measured at different levels of ventilation of right lung. RESULTS: After
      the left side ateloctasis during resting condition, the right lung could
      compensate to produce only mild hypoxemia (PaO2 9 kPa). But with further
      increased ventilation by exercise the shunt increased (from 19% to 29%) and led
      to severe hypoxemia (PaO2 8 kPa). When an artificial pneumothorax was instituted
      on the left lung, the shunt decreased (from 29% to 18%) and PaO2 increased (from
      8 kPa to 9 kPa). CONCLUSIONS: After AUA, whether severe hypoxemia would occur is
      determined by the volume of ventilation of the normal side lung. The excess
      increase of ventilation of the normal side lung by any reason may result in
      severe hypoxemia.

PMID- 9275384
TI  - [Using ligustrazini and angelica sinensis treat the bleomycin-induced pulmonary
      fibrosis in rats].
AB  - OBJECTIVE: To seek a kind of Chinese traditional medicine to treat the bleomycin
      induced pulmonary fibrosis. METHODS: SD rats with bleomycin A(s) induced
      pulmonary fibrosis, were divided into 4 groups. Normal control group (10 rats),
      untreated model group (35 rats), ligustrazini group (10 rats), Angelica sinensis
      group (10 rats). Both ligustrazini and angelica sinensis were given
      intraperitoneally by injection daily for 28 days. Then all rats were put to death
      and took out the lungs for examination. Using histopathological examination and
      image processing computer assisted to evaluate the result of treatments. RESULTS:
      Ligustrazini could obviously reduced alveolitis and fibrosis and Angelica
      sinensis had the similar but lesser result. CONCLUSION: Ligustrazini and angelica
      sinensis have successful result of treatment for pulmonary fibrosis.

PMID- 9275385
TI  - [The prospect of prevention and treatment of Cor pulmonale on a 20-year follow-up
      of 40 middle to old aged cases of COPD and Cor pulmonale].
AB  - OBJECTIVE: To study the outcome of current therapy for COPD and Cor pulmonale by
      long-term follow-up of COPD patients. METHOD: Forty cases of middle to old aged
      COPD and Cor pulmonale patients were followed up for a period of 20 years.
      RESULTS: The pulmonary function of all the patients reduced significantly more
      than healthy elderly, while no difference was noted in blood gas analysis. 23
      patients with advanced COPD developed cor pulmonale, so that the number of cases
      with cor pulmonale increased significantly from 7 to 30. By the end of follow-up
      19 cases survived (48%), 21 cases (Cor pulmonale 19, COPD 2) died (53%).
      CONCLUSIONS: In view of the high mortality of cor pulmonale and the tremendous
      treatment cost, it was considered that the prospect for cor pulmonale management
      should be put on treating COPD to avoid development of Cor pulmonale. The keys of
      treating COPD are stop of smoking, protection from cold, early treatment of
      respiratory infection and further establishment of pulmonary rehabilitation work.

PMID- 9275386
TI  - [The relationship between the high inducibility genotype of CYP450IA1 and lung
      cancer susceptibility].
AB  - OBJECTIVE: To evaluate the role of polymorphism of CYP450IA1 gene in the
      susceptibility of lung cancer. METHODS: The polymorphism of CYP450IA1 gene in 149
      lung cancer patients and 208 healthy controls were investigated by PCR technique.
      RESULTS: The high inducibility genotype (Val/Val type) of CYP450IA1 in lung
      cancer patients was 16.1%, which was significantly higher than that of controls,
      8.7%. According to pathological classification of lung cancer, it was indicated
      that VAl/Val type in squamous carcinomas was the highest, 21.54%, which was
      significantly higher than that of controls (8.7%) and adenocarcinomas (8.00%).
      The Val/Val type in small cell carcinoma reached 17.6%. The relative risks were
      estimated according to smoking condition and CYP450IA1 genotype. Taking the risk
      of the category with non-smoking and non-high inducibility genotype (Val/ Val) to
      be at a baseline of 1.0, the odds ratio was 1.6 (P < 0.05) in non-smoking in non
      smoking and Val/Val type 4.8 in smoking and Val/Val type (P < 0.001). The
      relative risk of Val/Val type was 2.2 times as non-Val/ Val type for smoking
      people. CONCLUSIONS: Development of lung cancer was associated with the high
      inducibility genotype of CYP450IA1. And Val/Val genotype of CYP450IA1 gene might
      be an important host hereditary marker for susceptibility to lung cancer.

PMID- 9275387
TI  - [Detection of Mycobacterium tuberculosis in clinical samples by PCR and DNA
      probe].
AB  - OBJECTIVE: To improve the sensitivity and specificity of polymerase chain
      reaction (PCR) for detecting M. tuberculosis in uncultural clinical samples.
      METHODS: PCR amplification products were identified with agarose gel
      electrophoresis (PCR-electrophoresis), then Southern blotted onto a membrane and
      hybridized with a digoxigenin-labeled M. tuberculosis DNA probe (PCR-probe).
      RESULTS: The sensitivity of the purefied DNA for PCR-electrophoresis was 1
      picogram, that for PCR-probe was increased to 100 femtogram. In 24 species
      tested, only M. tuberculosis complex and M. xenopi DNA produced 245-bp
      amplification bands, but the band from M. bovis did not hybridize with 188-bp
      digoxigenin-labeled probe. 225 clinical samples were examined by smear, PCR
      electrophoresis and PCR-probe, 51 nontuberculous clinical samples were all
      negative, the positive rates of 173 tuberculous samples were 16.2%, 37.6% and
      50.3%, respectively. The smear and culture of 1 sputum sample from a patient
      infected by nontuberculous mycobacteria were all positive, but its PCR
      electrophoresis and PCR-probe were all negative. Identification of species showed
      that it was a quickly growing mycobacterium. Otherwise, the figures of
      electrophoresis were classified as four types, and influential factors were also
      discussed. CONCLUSIONS: The results showed that PCR was a valuable detective tool
      for early diagnosis and differential diagnosis of tuberculosis, and PCR-probe
      could increase positive rate of the detection and avoid misjudgements of results.

PMID- 9275388
TI  - [Detection of lipoarabinomannan-IgG in serum for the diagnosis of pulmonary
      tuberculosis].
AB  - OBJECTIVE: To ascertain the value of lipoarabinomannan-IgG (LAM-IgG)
      determination in the diagnosis of pulmonary tuberculosis. METHOD: LAM-IgG in sera
      obtained from 90 patients with active pulmonary tuberculosis, 53 patients with
      lung cancer and 30 healthy individuals were detected by using rapid enzyme-linked
      immunosorbent assay (ELISA). RESULTS: The positive rate was 82% in tuberculosis
      group, and the false positive rates were 8% and 3% in cancer group and healthy
      controls respectively. CONCLUSION: The results suggested that rapid ELISA and LAM
      IgG detection was a useful supplementary tool for diagnosis of pulmonary
      tuberculosis.

PMID- 9275389
TI  - [Study on the level of soluble interleukin-2 receptor, expression of membrane
      interleukin-2 receptor and T lymphocyte subpopulations in pulmonary
      tuberculosis].
AB  - OBJECTIVE: To evaluate the significance of soluble interleukin-2 receptor (sIL
      2R), membrane interleukin-2 receptor (mIL-2R) and T lymphocyte subpopulations in
      development of pulmonary tuberculosis. METHODS: The level of sIL-2R, expression
      of mIL-2R and the profile of T lymphocyte subpopulations in patients with
      pulmonary tuberculosis were tested by sandwiched ELISA and alkaline phosphatase
      antialkaline phosphate (APAAP) methods. RESULTS: The levels of sIL-2R, CD8 were
      higher, and expression of mIL-2R, CD4, CD4/CD8 ratio were lower in pulmonary
      tuberculosis than those in normal controls (P < 0.001). And the changes of all
      indicators in patients with cavitation were more obvious than those in patients
      without (P < 0.001), the changes in progressive stage were more obvious than
      those in stable and improving stages (P < 0.001). CONCLUSION: The results
      indicated that the patients, condition and prognosis of pulmonary tuberculosis
      were related to the changes of sIL-2R level, mIL-2R expression and T lymphocyte
      subpopulations.

PMID- 9275390
TI  - [Surgical treatment and classification of spontaneous pneumothorax caused by
      break-up of bullae].
AB  - OBJECTIVE: To explore the appropriate operation for surgical treatment and a
      better classification for spontaneous pneumothorax caused by break-up of bullae.
      METHODS: Eighty two cases of spontaneous pneumothorax caused by break-up of
      bullae were reported and classified by their clinical characteristics and
      manifestations during operation. RESULTS: All cases were classified into type I
      (apical), type II (lobular), type III (diffusive) and type IV (bilateral) on the
      basis of bullae's appearance and location. And the cases of type I were further
      classified into Ia (simple) and Ib (pneumohemothoracic). CONCLUSION: The clinical
      classification was thought to be valuable for diagnosis and treatment of
      spontaneous pneumothorax caused by break-up of bullae.

PMID- 9275391
TI  - [Endoscopic sinus surgery for sinusitis].

PMID- 9275392
TI  - [Observation on nasal mucociliary ultrastructure of ostiomeatal complex].
AB  - Functional endoscopic sinus surgery (FESS) was performed on 35 patients who
      suffered. from chronic nasosinusitis. All patients recovered six months after
      operation. During FESS, 10 specimens of pathological mucosa were obtained near
      the ostium of maxillary sinus. Scanning electron microscope and transmission
      electron microscope were used to observe pathological changes of mucociliary
      ultrastructure. The results indicate that FESS is easier, safer and more
      practicable surgery than traditional one. The pathological changes observed
      include loss of cilia, disorientation, short cilia and tubular abnormalities.
      These ultrastructural changes are believed to be the results of long-term
      inflammation in the nose and paranasal sinuses.

PMID- 9275393
TI  - [Study of amount of bleeding in endoscopic sinus surgery].
AB  - The amount of bleeding and its relative factors were statistically analysed. The
      result showed that amount of bleeding was closely related to following factors,
      time of operation, type of anesthesia, pattern and duration of surgical
      procedure, and skill of surgeons. The non-elasticity of blood vessels in scar
      tissue, and abnormal vessels in hyperplastic pathologic tissue were the most
      important factors which induced bleeding in patients for revision surgery. In
      order to reduce bleeding, some devices were suggested.

PMID- 9275394
TI  - [Effects of endoscopic sinus surgery and relative factors].
AB  - The results of 296 endoscopic sinus surgery (ESS) from Oct. 1991 to May, 1993
      were analysed. Pre- and post-operative examinations in this series were as
      follows: 1. Peripheral blood T lymphocyte subclusters test (100 cases): 2.
      Immunohistochemical test of nasal polyp (103 cases): 3. Pathologic examination of
      nasal polyp: 4. CT scan typing (103 cases). Men and women ratio was 2:1 and their
      ages varied from 7 to 72 years. 107 patients were given general anesthesia and
      189 patients local anesthesia. The clinical stages of chronic sinusitis were
      divided as: 53.7% (N), 29.3% (II), 10.9% (III) and 6.1% (I). The clinical
      curative rate was 85.7% (126/147 cases), and improving rate was 99.3%. The
      standard of clinical stage of chronic sinusitis, the relative factors of
      prognosis with the results of ESS, pathological test, immunohistochemical test
      and follow-up after ESS were discussed.

PMID- 9275395
TI  - [Treatment of cerebrospinal rhinorrhea under nasal endoscope with EC ear-head
      adhesive].
AB  - Five cases of cerebrospinal rhinorrhea in frontal, ethmoid or sphenoidal sinus
      were repaired under endoscope with ear-head adhesive with satisfactory results.
      The advantages of the method are as follows: (1) The sufferings of the patient
      are minor and intercranial complications are fewer: (2) The location and size of
      the fistula are clear under endoscope: (3) The success rate is higher due to the
      application of ear-head adhesive: (4) With the use of muscles and fasciae outside
      the nose, the bleeding in nasal cavity may be avoided: (5) The curettages of the
      mucosa around the fistula and dura mater is helpful to the adherence of ear-head
      adhesive with these tissues.

PMID- 9275396
TI  - [Endoscopic sinus surgery, clinical aspect with 69 cases].
AB  - Sixty-nine patients (121 sides) received endoscopic sinus surgery between May,
      1993 and October, 1994. All of the patients exhibited following clinical signs:
      bilateral or unilateral nasal polyps and paranasal sinusitis. There were 43 men
      and 26 women, ranging in age from 14 to 68 years. Among the patients, 14 (25
      sides) were treated with functional ethmoidectomy; 33 (59 sides) with total
      ethmoidectomy; and 21 (36 sides) with sphenoethmoidectomy. 23 patients (36 sides)
      were treated simultaneously with radical maxillary sinus surgery. According to
      the data of postoperative follow-up, nasal obstruction disappeared completely in
      57 cases (57/59); headache remitted in 51 (51/56); and 35 (35/54) were free of
      purulent nasal discharge. No severe complications were observed. The incidence of
      residual and recurrent polyp were 12.39% (15/121 sides). The curative effect of
      endoscopic sinus surgery was analysed. The indications of operation, the
      preoperative CT scan of paranasal sinuses, and the endoscopic techniques were
      discussed.

PMID- 9275397
TI  - [Electrical response recording of cochlear hair cells in vivo].
AB  - Intracellular recordings were made on cells of Corti organ from low-frequency
      region (third turn) of guinea pig cochlea, the recording sites being confirmed by
      HRP injection and subsequent histology. Response characteristies of the hair
      cells were studied. The Inner hair cells (IHCs) possessed relatively low resting
      membrane potentials in contrast to higher ones of OHCs. The receptor potentials
      from both cell types, in response to tone bursts, consisted of a combination of
      AC and DC components. For the low-frequency region, the receptor potentials were
      dominated by AC component. The causes of recording failure were discussed.

PMID- 9275398
TI  - [Observation on activity of carbonic anhydrase in the vestibule of guinea pigs].
AB  - The localization of carbonic anhydrase (CA) activity in the inner ear vestibule
      of guinea pigs were studied by histochemistry and cytochemistry. We found that
      numerous enzymatic reaction products were localized in the sterecocilia, cuticles
      of hair cells, no reaction product was seen in their cell bodies; revealed
      reaction products in the cell membrane, microvilli, lateral infolding and
      basolateral infolding of the supporting cell, dark cell, transitional cell and
      wall cell. It is suggeated that the CA is a membrane-associated CA and the
      membrane-associated CA plays an important role in the homeistasis of the
      vestibule and otolithic metabolism.

PMID- 9275399
TI  - [The experimental treatment of laryngeal cancer using local draining lymph node
      lymphocytes].
AB  - In order to know whether laryngeal cancer draining lymph node lymphocytes (INL)
      have antitumor effects in vivo, we transfered IL-2 activated LNL to nude mice
      with human laryngeal squamous cell carcinoma line PHC3 xenografts, and observed a
      suppressive effect on tumor growth. It was also found in the epitype changes of
      LNL by indirect immunofluorencence method the major composition of freshly
      isolated LNL was CD3+ T cells in which there were more Th/i cells than Ts/c
      cells, CD4+/CD8+ ratio was 3.30 +/- 0.653. No evidence of lymphocytes
      multiplication or CD3+, CD4+, CD8+ epitype changes was found after short term IL
      2 culture, but we found more HLA-DR+, CD25+ cells which means there was an
      increase in activated lymphocytes after culture. The experiment suggests that
      laryngeal cancer draining lymph node lymphocytes have antitumor effects in vivo
      after IL-2 short term culture, and can be used in clinical immunotherapy.

PMID- 9275400
TI  - [Laryngeal reinnervation by nerve-muscle multipedicle transfer].
AB  - Abductive ability was restored by means of a modified nerve-muscle pedicle
      technique, utilizing nerve-muscle multipedicle and multipoint implantation in
      seventeen dogs. The results showed that the procedure was superior to traditional
      Tucker's technique in functional recovery, electrophysiological activity and
      muscle strength which was also demonstrated by histochemical studies. There was
      little difference between double and three nerve-muscle pedicle transfer. The
      procedure has been used in three patients with bilateral vocal cord paralysis.
      Return of spontaneous abduction in the operated side in two patients was noted
      after eight and twelve weeks after surgery. All patients have achieved sufficient
      airway without the need of tracheotomy. Electromyography confirmed the
      reinnervation of posterior cricoarytenoid muscle.

PMID- 9275401
TI  - [Restoration of external auditory canal by filling mastoid cavity with carbon
      pellet].
AB  - To prevent infection of an open mastoid cavity after mastoidectomy and improve
      hearing, the external auditory canal had been maintained on 72 cases (73 ears) by
      filling mastoid cavity with carbon pellet. The average duration of dry ear after
      operation was 25 days with a dry ear rate being 98.6%. No phenomenon of rejection
      and falling out appeared within 1-7 years follow-up. Carbon pellet has advantages
      of chemical stability, nontoxicity, good histocompatability, anti-fatigue
      characteristic in body fluid, and anti-corrosive effect against acid, base and
      salt.

PMID- 9275402
TI  - [The analysis of abnormal auditory brainstem responses].
AB  - The abnormal auditory brainstem responses (ABR) of 56 cases who had different
      retrocochlear disorders were analysed. These disease included acoustic neuroma,
      glioma, cholesteatoma, astrocytoma, meningoma in cerebellopontile angle (CPA),
      chromaffin tumor of jugular foramen, intracranial metastatic tumor, demyelinating
      disease, multiple cranial nerve paralysis, hepatolenticular degeneration, other
      CPA tumors, expansion or stenosis of internal auditory meatus (IAM), and so on.
      The ABR features were varied in these diseases, even in same disease. In general,
      the wave latencies and interwave periods prolonged in the disorders which
      occupied place in CPA, the differentiation of wave was not clear and/or the wave
      was not well repeated in the disorders which spreaded all over the brain. The
      cause of abnormal ABRin which CT and/or MRI were normal was also analysed. The
      ABR detection is a sensitive indication in retrocochlear lesions.

PMID- 9275403
TI  - [The use of hyoid osteomuscular flap in extended partial laryngectomy].
AB  - The surgical defect after conventional partial laryngectomy practically needs no
      special technique to repair. On conservation surgery for late (T3 and T4) cases a
      large part of the larynx is to be resected so that the margin of surgical
      clearance is ample and, at the same time, an appropriate method of reconstruction
      is mandatory to restore the essential functions of the larynx. For this purpose
      we developed a technique of osteomuscular flap to repair the defect left behind
      after a three-fourths laryngectomy (for supraglottic case) or an extended
      vertical partial laryngectomy (for glottic case). In both cases the arytenoid
      cartilage or the cricoarytenoid joint was resected to ensure the safety margin of
      resection. The mylohyoid muscle was severed at the upper border of the body of
      the hyoid bone. A small piece of the hyoid bone (about 5 mm) and its attached
      strap muscles were used. The muscles were made a 90 degree bent toward the
      laryngeal cavity. The hyoid bone was used to substitute the removed arytenoid and
      the muscles to bridge over the laryngeal lumen. The postericoid mucosa was
      advanced to cover the transplanted hyoid bone. Then the cut edge of the thyroid
      cartilage was lifted up and sutured with the base of the tongue to close the
      wound. 108 cases were treated within a period of 12 years (1979-1990). The three
      year survival rates for stage II and stage IV of supraglottic type (66 cases)
      were 78.6% and 66.7% respectively, and for stage II of glottic type (42 cases),
      79.3%. The decannulation rate was 75%-85%, and 80% of the patients enjoyed a
      socially acceptable voice. All cases resumed normal mouth-food-taking.

PMID- 9275405
TI  - [Magnetic resonance imaging of laryngeal cancer].
AB  - MRI data of twenty-four cases of laryngeal cancer were analysed and compared with
      the findings of postsurgical pathology. The results revealed that MRI could
      clearly demonstrate the three dimensional representations of tumor pathology, and
      correctly depict invasion of paraglottic space (PGS), and preepiglottic space
      (PES), and precisely display involvement of laryngeal cartilage by cancer. It was
      considered that MRI was of great importance in determining appropriate therapy
      for laryngeal cancer.

PMID- 9275404
TI  - [The detection of laryngeal carcinoma-associated antigens in tissue and serum
      using three mixed monoclonal antibodies against laryngeal cancer].
AB  - Laryngeal carcinoma-associated antigens in tissue and serum of patients with
      laryngeal carcinoma and normal adults were detected by using ABC and ELISA
      methods. The results showed that the positive rate rised from 80-86.6% to 97.7%
      by applying mixed monoclonal antibodies compared with single monoclonal antibody
      against laryngeal cancer. It was also found that the level of laryngeal carcinoma
      associated antigens was much higher in serum of laryngeal carcinoma group than
      that of control group. The statistic difference was very significant (P < 0.01).
      The level was different with clinical types, stages and increased in line with
      the tumor growth. So it was suggested that the mixed monoclonal antibodies were
      sensitive and specific, which was considered as a useful tumor marker for
      diagnosis, monitoring clinial course and judging prognosis of patient with
      laryngeal carcinoma.

PMID- 9275406
TI  - [Wound infection and recurrence after total laryngectomy].
AB  - 95 patients who received total laryngectomy for laryngeal carcinoma were
      reviewed. They were divided into two groups, those with postoperative wound
      infection and those without. The relations between postoperative wound infection
      and local recurrence were discussed. The results showed that the recurrence rate
      of postoperative infection group was higher than that of no postoperative
      infection (P < 0.001), and the patients with gram-negative bacilli infection also
      had much higher recurrence rates (P < 0.05). For the laryngeal cancer, the
      development of a wound infection after total laryngectomy may be related to the
      local tumour recurrence within one year.

PMID- 9275408
TI  - [Comprehensive staging laparotomy in stage I epithelial ovarian cancer].
AB  - OBJECTIVE: To evaluate the significance of comprehensive staging laparotomy in
      stage I epithelial ovarian cancer. METHODS: Forty-three patients with stage I
      epithelial ovarian cancer were divided into 3 groups and retrospectively
      analysed. Thirty two of these patients allotted to stage I ovarian cancer
      according to FIGO criteria were ascertained by comprehensive staging laparotomy
      (group A), 5 patients were upstaged following comprehensive staging laparotomy
      (group B) and 6 patients were staged without comprehensive laparotomy (group C).
      RESULTS: The mean operation time was 2 hours and 40 minutes, the mean volume of
      blood loss was 460 ml and no severe complications occurred during the
      comprehensive staging laparotomies. 13.5% (5/31) of patients were found to have
      retroperitoneal metastasis and then therefore were upstaged as stage III. Group A
      and B had better prognosis. During the 39.7 months followup period, tumor-free
      survival rates in group A and B were 97% (31/37) and 5/5 respectively. In group
      C, 2 patients recurrent and one died of the diseases, a tumor-free survival rates
      of 4/6. There was a significant difference in tumor-free survival rates between
      group A and C (P = 0.038). CONCLUSION: Comprehensive staging laparotomy should be
      considered as an important criterion in FIGO staging of epithelial ovarian cancer
      and a standard procedure in the treatment of stage I epithelial ovarian cancer.

PMID- 9275407
TI  - [A rational treatment of stage I epithelial ovarian cancer].
AB  - OBJECTIVE: To evaluate the incidence of lymph node metastasis and the role of
      lymphadenectomy in stage I epithelial ovarian cancer. METHODS: Forty patients
      with stage I epithelial ovarian cancer treated from 1985 to 1990, were divided
      into two groups and retrospectively analyzed. First group of 20 patients were
      treated by routine surgery and cis-platinum based chemotherapy. Second group of
      20 patients were treated by routine surgery and cis-platinum based chemotherapy
      plus retroperitoneal lymphadenectomy, and on the basis of with normal ovary and
      uterus preserved in the younger stage I a patients. A comparison was made between
      the five-year survival rates of the two groups. RESULTS: Four patients in the
      second group were found to have retroperitoneal lymph node metastasis and should
      be staged as II c postoperatively. In three of the four patients aortic lymph
      node metastasis were diagnosed. The chances of metastasis to the pelvic and to
      the aortic lymph nodes were nearly equal. There is a significant difference in
      the 5-year survival rates between the two groups (85% vs 100%, P < 0.05). Ten
      patients with their ovaries and uteri preserved are living and well. CONCLUSION:
      It is suggested that to obtain accurate FIGO staging and to improve survival and
      its quality, retroperitoneal lymphadenectomy should be performed in all patients
      with stage I eipthelial ovarian cancer, and younger patients with stage I a
      cancer may preserve their gestational functions if desired.

PMID- 9275409
TI  - [Epidemiology of gastroschisis in China].
AB  - OBJECTIVE: To study the clinical and epidemiologic characteristics of perinates
      with gastroschisis (GA) in China. METHODS: The birth defects monitoring program
      was undertaken in 945 hospitals from 29 provinces, cities and autonomous regions
      of China. Data about perinates including intrauterine death and stillbirth from
      28 weeks of gestation to a period of 7 days after birth was collected through the
      medical records between October 1986 and September 1987. RESULTS: A total of 194
      cases with GA was found in 1243284 perinates monitored. The incidence of GA in
      China varied from 0.4 to 3.4 with a mean of 1.6 per 10,000. The highest
      prevalence was in Shandong province (3.4/10,000) which was significantly higher
      than the average (P < 0.01). The prevalence of GA perinates with low birth weight
      was higher than that with normal birth weight (1.6 vs 0.6 per 10,000, P < 0.01),
      as well as that in the rural area higher than in the urban area (2.5 vs 1.1 per
      10,000, P < 0.01). 70.6% of the cases with GA were accompanied with other major
      defects. The overall perinatal mortality rate (PMR) of GA was 91.8%. PMR of GA
      with other birth defects (95.6%) was significantly higher than that of GA only
      (82.5%, P < 0.01). Only 15% of GA were diagnosed before birth. CONCLUSIONS: GA
      was a serious malformation. Cases with GA had high PMR and low detection rates in
      prenatal diagnosis, and most often accompanied with multiple defects.

PMID- 9275410
TI  - [Detection of the mutational gene in phenylketonuria and prenatal diagnoses by
      using single strand conformation polymorphism methods].
AB  - OBJECTIVE: To establish rapid methods for the detection of gene mutations and
      prenatal diagnosis of phenylketonuria (PKU). METHODS: The single strand
      conformation polymorphism (SSCP) combined with silver staining technique were
      used to screen the mutations in the four exons of phenylalanine hydroxylase (PAH)
      gene. After the polymerase chain reaction, the DNA fragments were separated by
      electrophoresis on polyacrylamide gel containing glycerol and visualized by
      silver staining. RESULTS: Three known missense mutations which are R243Q
      (E7)[CGA(Arg243)-->CAA (Gln)], R413P(E12) [CGC(Arg413)-->CCC(Pro)] and
      Y356X(E11)[TAC(Tyr156)-->TAA(Ter)] were detected in 21 degrees C, 28 degrees C
      and 7 degrees C. Three kinds of unknown abnormal DNA bands in exon 10 were
      detected in 21 degrees C. The mutations of 13 PKU families have been detected.
      Prenatal gene diagnoses were successfully performed in 5 pregnancies at risk with
      PKU. CONCLUSION: The method is very useful for detecting the mutations and
      prenatal diagnoses of PKU families.

PMID- 9275411
TI  - [Study on sister chromatid exchange in lymphocytes of women with fetal
      intrauterine growth retardation].
AB  - OBJECTIVE: To study sister chromatid exchange (SCE) frequency in lymphocytes of
      pregnant women with intrauterine growth retardation (IUGR) infants. METHODS: The
      frequency of SCE in peripheral blood lymphocytes of 14 pregnant women with IUGR
      babies and 90 normal pregnant women as well as the umbilical blood of their
      infants were investigated. RESULTS: The mean frequency of SCE in maternal and
      umbilical blood with normal pregnancy were 7.58 +/- 0.32 and 5.05 +/- 0.29
      respectively, while they were 10.53 +/- 2.69 and 7.25 +/- 1.34 in IUGR group
      respectively. The difference of SCE levels between the 2 groups of mother was
      statistically significant (P < 0.01), so was that of the umbilical blood group.
      CONCLUSION: One of the causes of IUGR may be related to heredity injury. Thus,
      SCE will be a new diagnostic index to predict IUGR.

PMID- 9275412
TI  - [The detection and clinical significance of nitric oxide synthetase activity in
      placenta tissue].
AB  - OBJECTIVE: To study the role of nitric oxide (NO) secreted by placenta tissue in
      pregnancy. METHODS: The activity of nitric oxide synthetase (NOS), the
      concentration of malondialdehyde (MDA) and the activity of superoxide dismutase
      (SOD) in placental tissue were measured in 37 normal pregnant women at various
      gestational ages and in 6 patients with pregnancy induced hypertension (PIH).
      RESULTS: The activity of NOS decreased with the advancement of pregnancy. It was
      higher in normal mid and late pregnancy than that in PIH. In normal pregnancy,
      there was positive correlation between the activity of NOS and the activity of
      SOD (r = 0.3588, P < 0.05), and birth weight as well (r = 0.4340, P < 0.05).
      Negative correlations between the activity of NOS and the concentration of MDA (r
      = 0.4355, P < 0.05), and gestational age (r = -0.4742, P < 0.05) were found.
      CONCLUSION: NOS secreted by placenta may play an important role in regulating the
      process of pregnancy and the pathogenesis of PIH.

PMID- 9275413
TI  - [The influence of surfactant on the alveolar morphology in premature rabbits].
AB  - OBJECTIVE: To study the effects of treatment by surfactant manufactured by our
      institute on premature rabbits through observation of alveolar morphologic
      changes. METHODS: The morphology of alveolar area in the premature rabbits were
      quantitatively studied by morphometry. RESULTS: In the surfactant treated group,
      there was a reduction of alveolar number, and increases in alveolus area and the
      ratio of alveolus to alveolar septum. These changes were better than that in the
      control group. CONCLUSION: Our surfactant was effective for respiratory distress
      syndrome in premature rabbits.

PMID- 9275414
TI  - [Effects on fetal and infant's development of intrauterine cytomegalovirus
      infection].
AB  - OBJECTIVE: To study the early effects of fetal development and remote sequalae of
      mental development of infants after intrauterine human cytomegalovirus (HCMV)
      infection. METHODS: Enzyme-linked immunoabsorbant assay (ELISA) were used for
      screening HCMV antibodies in the serum of 1419 pregnant women. HCMV DNA were
      examined by PCR in maternal blood, amniotic fluid and/ or umbilical blood for
      those with serum HCMV-IgM positive and some with HCMV negative. According to the
      results, group A (n = 53) included women with positive serum HCMV-IgM and HCMV
      DNA, and also positive HCMV DNA in amniotic fluid and/or umbilical blood: group B
      (n = 87) were women with positive serum HCMV-IgM and HCMV DNA but negative HCMV
      DNA in amniotic fluid and/or umbilical blood: group C (n = 34) served as control
      with all negative. The above 174 cases were carefully monitored for fetal
      development. Baley scales of infant development (BSID) were used to test both
      mental development index (MDI) and psychomotor development index (PDI) at 2-30
      months after birth for babies in group A and C. RESULTS: The occurrences of fetal
      intrauterine death, congenital malformation, fetal growth retardation and
      neonatal asphyxia were significantly higher in group A than that in group B and C
      (P < 0.05) and the average birth weight and height were also significantly lower
      in group A (P < 0.05). The mental development of infants in group A were
      remarkably slower than that of group C (P < 0.01). CONCLUSION: Active HCMV
      intrauterine infection may cause congential infection, birth defects and mental
      retardation in childhood.

PMID- 9275415
TI  - [Analysis of obstructive dystocia due to cervical adhesion caused by gonococcal
      infection].
AB  - OBJECTIVE: To analyse the clinical manifestation and treatment of obstructive
      dystocia due to cervical adhesion. METHOD: Ten cases of obstructive dystocia due
      to cervical adhesion were retrospectively analysed. RESULTS: Gram's stain of the
      cervical smear was positive for gonococci in all of the 10 patients. Sites of the
      cervical adhesion were at external os in 5 cases, at internal os in 2 cases and
      in cervical canal in the other 3. The clinical manifestation varied with the site
      of the cervical adhesion. All the patients had spontaneous delivery after
      separating the adhesions. CONCLUSION: As one of the factors of high-risk
      pregnancy, obstructive dystocia due to cervical adhesion caused by gonococcal
      infection should be considered seriously by the obstetricians.

PMID- 9275416
TI  - [Persistent and recurrent gynecologic malignant tumor treated within one year:
      analysis of 1,753 cases from 61 hospitals in China].
AB  - OBJECTIVE: To analyze the causes of persistent and recurrent gynecologic
      malignant tumors treated within 1 year. METHODS: 20,974 cases of gynecologic
      malignant tumors from 61 hospitals in 24 provinces admitted between 1983-1993
      were collected. Out of the total, 1753 cases treated within 1 year with tumor
      persistence, recurrence or death were retrospectively analysed. RESULTS: The
      ovarian carcinoma and vaginal cancer had the highest rates of tumor persistence,
      recurrence or death. Among the 1587 cases of tumor persistence or recurrence,
      pathological grading were not performed in 56.52% of the cases. For surgical
      treatment, inappropriate operation were done in 81.68% (767/939) of the ovarian
      carcinoma, 64.38% (103/160) of the cervical carcinoma, and 70.08% (89/127) of the
      endometrial cancer. 55.47% (532/959) of ovarian cancer and 38.31% (59/154) of
      choriocarcinoma and malignant mole had insufficient chemotherapy. For cervical
      cancer, 54.90% (235/396) of the cases did not receive enough doses of
      radiotherapy. CONCLUSION: Accurate staging and standardized therapy are important
      for improving 1 year survival rate in malignant gynecologic tumors.

PMID- 9275417
TI  - [Ovarian renin-angiotensin system].

PMID- 9275418
TI  - [Advances in the therapy of malignant ovarian germ cell tumors].

PMID- 9275419
TI  - [Contraceptive research and development].

PMID- 9275420
TI  - [The morphometric study of endometrium during long-term use of TCu220C IUD].
AB  - OBJECTIVE: To observe the pathological changes of endometrium in women using
      TCu220C intrauterine devices (IUD) for 5-12 years, and to judge its long term
      safety. METHODS: A hundred women using TCu220C IUD for 5-12 years were randomly
      selected as IUD group. Samples of endometrium from the sites compressed by IUD
      and 1 cm apart were taken under hysteroscopy during proliferative phase. Another
      100 women matched in age but not IUD users served as control group, and
      endometriums were taken by curettage. All the samples were studied for
      morphometry. RESULTS: All pathological changes were localized in the areas of
      endometrium in direct contact with IUD but not the adjacent areas. Inflammatory
      reactions mainly lymphocytes infiltration were seen in all IUD samples with depth
      of 0.91-1.20 mm. Atrophy was seen in 25% of the cases using IUD for 5-10 years
      with an average area of 0.81 mm2, while in 71% of those using IUD for 10-12 years
      with an area of 1.50 mm2. Fibrosis was shown in 18% of the cases using IUD for 5
      10 years with area of 1.87 mm2, and 100% in 10-12 years with area of 2.04 mm2.
      There was no hyper-proliferation and malignant changes in IUD group. Hemorrhage
      and necrosis existed in all cases using IUD for 10-12 years. In the IUD group all
      the cases showed asynchronization of endometrium. CONCLUSION: It is safe for
      women using TCu220C IUD for 5-12 years. Since endometrial hemorrhage and necrosis
      were shown in women using IUD over 10 years, it is better to remove the IUD after
      10 years if they have clinical symptoms.

PMID- 9275421
TI  - [Three dimensional reconstruction of human endometrial spiral arteries
      preinsertion and postinsertion of IUD].
AB  - OBJECTIVE: To investigate the micro-three dimensional changes of endometrial
      spiral arteries after insertion of different intrauterine devices (IUD). METHODS:
      Nine endometrium specimens were obtained from fertile age women, 3 from
      preinsertion, 3 obtained 3 months after insertion of TCu220C IUD, and 3 specimens
      obtained 3 months after insertion of gamma Cu IUD (releasing indomethacin 20
      micrograms/day). All samples were collected in late secretory phase and were
      sectioned serially. By a TV camera, the images of sections were sent from a light
      microscope to a computer and converted into digital data. The spiral arteries of
      endometrium were reconstructed and visualized on a workstation by means of the
      software package for the three dimensional reconstruction and visualization. The
      curvature and torsion of the spiral arteries were calculated. RESULTS: In
      preinsertion group, the spiral arteries curved regularly in three dimensions, and
      the average diameter was 22.69 microns, the average curvature was 0.96 and the
      average torsion was 1.27. The spiral arteries of gamma Cu IUD group had similar
      appearances as the preinsertion group. However, in TCu220C IUD group, the curves
      were irregular, and the average diameter was 17.99 microns, the average curvature
      was 1.48 and average torsion 1.86. CONCLUSION: The three dimensional
      reconstruction of human endometrial spiral arteries was done by means of
      computerassisted reconstruction technology for the first time. The endometrium
      spiral arteries changed in morphology after insertion of copper IUD, and
      indomethacin may have contrary effects on copper.

PMID- 9275422
TI  - [Emergency contraception with mifepristone and anordrin].
AB  - OBJECTIVE: To study the efficacy of mifepristone or with anordrin for emergency
      contraception. METHODS: 300 healthy women were recruited within 7.2 hours after
      unprotected intercourse or contraceptive failure and randomly allocated into 3
      groups. Group 1 (n = 100), mifepristone 25 mg twice with 12 hours apart; group 2
      (n = 99), single dose of mifepristone 25 mg; and group 3 (n = 101), mifepristone
      25 mg and anordrine 7.5 mg given once. RESULTS: No pregnancy occurred in group 1,
      while 1 pregnancy in each group 2 and 3. The contraceptive effectiveness were
      100.0%, 83.8% and 86.1% for the 3 groups respectively. The overall menstruation
      disturbances and side effects were low. CONCLUSIONS: Both mifepristone 50 or 25
      mg were effective for emergency contraception and no synergetic effects of
      anordrin in combination with mifepristone was shown in this study.

PMID- 9275423
TI  - [Effects of levonorgestrel subdermal implants on estradiol and progesterone
      receptors of endometrium and ovarian tissues in rats].
AB  - OBJECTIVE: To study the influence of subdermal implantation of levonorgestrel
      (LNG) on the levels of estradiol receptor (ER) and progesterone receptor (PR) in
      ovaries and endometrium of rats. METHODS: 45 female mature rats were divided into
      3 groups: control group, silicon tube group and LNG implants group. Using single
      point determination at saturating concentration method, ER and PR levels of both
      ovaries and endometrium were measured at 15, 30 and 45 days after subdermal
      implantation of LNG or silicon tube, and compared with that of the control group.
      RESULTS: ER and PR levels in LNG group were significantly lower than those in the
      other 2 groups (P < 0.01). The concentration of ER and PR decreased gradually as
      implantation prolonged. CONCLUSION: subdermal implantation of LNG resulted in the
      reduction of ER and PR levels in ovaries and endometrium of rats, which may be
      related to the mechanism of contraception and breakthrough bleeding after
      implantation.

PMID- 9275424
TI  - [Changes in endothelin-1 and atrial natriuretic peptide in peritoneal fluid of
      pelvic venous congestion syndrome after tubal sterilization].
AB  - OBJECTIVE: To demonstrate the presence of endothelin-1 (ET-1), atrial natriuretic
      peptide (ANP) in peritoneal fluid of women and their effects on pathogenesis of
      pelvic venous congestion syndrome after sterilization (PVCSS). METHODS: This
      randomized controlled study determined the concentrations of ET-1 and ANP in both
      peritoneal fluid and plasma, counts of macrophage in peritoneal fluid and volumes
      of peritoneal fluid in 21 cases of PVCSS. 12 normal women after sterilization and
      11 normal women as control in early follicular phase by radioimmunoassay.
      RESULTS: concentrations of ET-1, ratio of ET-1/ANP and counts of macrophage in
      peritoneal fluid with PVCSS were lower than those in control (P < 0.005, P <
      0.001, P < 0.001) and all had significant negative correlation with scores
      quantifying the severity of PVCSS (P < 0.05), but volumes of peritoneal fluid in
      PVCSS were larger than that in control (P < 0.001); counts of macrophage in
      peritoneal fluid had significant positive correlation with the concentrations of
      ET-1 of peritoneal fluid in all the three groups (P < 0.05); plasma
      concentrations of ET-1 and ANP didn't show any significant differences among the
      three groups (P > 0.05). CONCLUSIONS: ET-1 was present in peritoneal fluid of
      normal women. Lower concentrations of ET-1 and (or) lower ratio of ET-1/ANP in
      peritoneal fluid contributed to the pathogenesis of PVCSS.

PMID- 9275425
TI  - [Management of pituitary adenoma in pregnancy].
AB  - OBJECTIVE: To discuss the management of pituitary adenoma during gestation, labor
      and lactation. METHODS: This is a clinical retrospective analysis. 41 cases of
      pituitary adenoma in pregnancy and their treatment before conception and outcomes
      of pregnancy were analyzed. RESULTS: (1) The incidence of pituitary adenoma in
      pregnancy was 1.02%. (2) Women received bromocriptin only before pregnancy
      accounted for 85.77%. (3) Neurological symptoms occurred in 39.03% of the
      patients during gestation. (4) 30 patients (73.17%) kept on bromocriptin
      treatment during pregnancy, and no adverse effects on fetus were seen. (5) 75.00%
      of the patients were breastfeeding and no abnormal symptoms were shown.
      CONCLUSION: Bromocriptin treatment during pregnancy was safe and effective for
      women with pituitary adenoma, and breastfeeding was not contraindicated.

PMID- 9275426
TI  - [The immuno-pathological damage of placenta and its types in pregnancy induced
      hypertension].
AB  - OBJECTIVE: To study the immuno-pathological damage to placenta and its types in
      pregnancy induced hypertension (PIH). METHODS: Using immunohistochemical
      technique (PAP method), authors studied the expression and localization of IgG,
      IgE, C3, C4, 5-HT on the villous vessels wall in PIH patients (n = 22) and normal
      pregnant women (n = 10), and observed the pathological changes of placenta with
      mast cell and connective tissue stain. RESULTS: The immunostaining of IgG, IgE,
      C3, C4, and 5-HT were seen in the wall of villous vessels in PIH patients, the
      strong positive rate were 100%, 90%, 100%, 100%, 90% in severe PIH patients
      respectively, accompanied by aggregation of mast cells and lesions of villi and
      villous arterioles. CONCLUSION: The immunological compound reaction and types 1,
      N of anaphylactic reactions took place in the placenta of PIH patients. It showed
      that the immunological factors were closely related to PIH.

PMID- 9275427
TI  - [A clinical study on the incidence of retroperitoneal lymph node metastasis and
      its risk factors in ovarian cancer].
AB  - OBJECTIVE: To investigate the incidence and the significant risk factors of
      retroperitoneal lymph node metastasis (LNM) in primary ovarian cancer for
      considering the necessity of systematic lymphadenectomy. METHODS: 117 cases of
      retroperitoneal lymphadenectomy performed on primary ovarian cancers in our
      hospital from November, 1987 to January, 1994 were studied. The relationship
      between clinicopathologic characters and the incidence of LNM were determined by
      univariate and multivariate analysis. RESULTS: In 44 (37.6%) of the 117 patients
      studied, LNM was confirmed pathologically. The chances of pelvic LNM (29.9%) were
      smilar to that of para-aortic LNM (20.9%) (P > 0.05). Univariate analysis showed
      that significantly increased incidence of LNM was clinically associated with
      bilateral involvement of the ovaries, presence of ascites, advanced stages, poor
      tumor differentiation, rather large residual tumors and some histopathological
      subtypes such as undifferentiated and serous adenocarcinoma. The size of the
      residual tumor, clinical stage and grade of differentiation were the most
      important risk factors for LNM (P < 0.05) by multivariate analysis. The
      indication, optimum time, the scope and model of systematic lymphadenectomy were
      evaluated and discussed. CONCLUSION: systematic lymphadenectomy was suggested
      only for early cases with high risk factors. For late cases with residual tumor
      the operation may be done at a chosen time, for instance, at second cytoreductive
      or second-look surgery.

PMID- 9275428
TI  - [The prospective study on the scope of extended operation for endometrial
      carcinoma].
AB  - OBJECTIVE: To investigate the scope of extended operation for endometrial
      carcinoma. METHODS: 105 patients underwent extended or less extended hysterectomy
      plus pelvic and/or para-aortic lymphadenectomy and 36 patients underwent less
      radical hysterectomy only. Prospective investigation of these 141 cases of
      endometrial carcinoma was undertaken. RESULTS: Of the 105 cases, lymph node
      metastasis (18.10%) occurred in 19 cases. Metastasis were found in all stages
      except stage Ia. The incidences of lymph node metastasis in stage Ib and stage Ic
      were 8.82% and 21.05% respectively. Of the 141 cases of extended or less extented
      hysteretomy, 2 were with parametrial connective tissue metastasis (stage II and
      stage III b), 2 with parametrial lymph node metastasis (stage I c and stage III
      b) and 2 with parametrial vascular involvement (stage I b and stage I c).
      CONCLUSIONS: The extended or less extended hysterectomy and lymphadenectomy
      should be performed in all patients of endometrial carcinoma except those of
      stage I a.

PMID- 9275429
TI  - [Clinicopathological features of human papilloma virus associated squamous cell
      carcinomas of the vulva].
AB  - OBJECTIVE: To investigate the relationship between human papilloma virus (HPV)
      status and clinicopathological features of vulva carcinoma and its clinical
      significance. METHODS: Histological sections of 37 cases of vulval carcinoma were
      subclassified. Standard PCR (HPV types 6/11, 16, 18) were applied to formalin
      fixed, paraffin wax sections. RESULTS: There were 24 cases of keratinizing
      squamous cell carcinoma (KSC), 7 cases of basaloid carcinoma (BC) and 6 cases of
      warty carcinoma (WC). HPVs, Mainly HPV 16, were detected in 10 of the 37 cases,
      and all of them were women with BC and WC types. Although BC and WC constituted
      35% of the total number of cases, the HPV detective rate was significantly higher
      than that of KSC (83.3% vs 0.0%), and the tumors were frequently accompanied by
      valvar intra-epithelial neoplasm (VIN). Clinically, women with BC and WC were
      younger than women with KSC (mean age at diagnosis for WC, BC and KSC were 36.7,
      58.9, 63.3 years respectively). Besides, the incidence of lymph node metastasis
      in BC and WC were lower than that in KSC (7.6% vs 25.0%). BC and WC were more
      likely to have another invasive or noninvasive squamous neoplasm of the cervix
      and vagina (3/13 vs 0/24), and recurrence rate was higher (12.5% vs 7.7%).
      However, their survival rates following surgical treatment of recurrences were
      also higher. Squamous cell carcinoma of the vulva are etiologically diverse
      tumors which have different clinical and pathological profiles. CONCLUSION: It is
      suggested that an etiological classification of squamous carcinoma of the vulva
      may at least be grouped at present into a small but substantial proportion (BC
      and WC) related to HPV and the majority portion (KSC) of unknown etiology.

PMID- 9275430
TI  - [Clinical study on immunotherapy of ovarian cancer with tumor infiltrating
      lymphocytes].
AB  - OBJECTIVE: To investigate clinical usage of ovarian tumor infiltrating
      lymphocytes. METHODS: Tumor infiltrating lymphocytes (TIL) were isolated by cold
      digestion method, specimens being taken from: (1) infiltrating node on tumor
      surface. (2) the tumor proper. (3) the ovarian tissue. A randomized, double-blind
      study on two groups on ovarian cancer, totally 25 patients was conducted. The
      first group was given TIL and chemotherapy and the second group was given
      chemotherapy only. RESULT: The yields of infiltrating node on tumor surface were
      the highest (7.24 x 10(5)), in the tumor proper (2.49 x 10(5)), and in the
      ovarian tissue the lowest (2.07 x 10(5)). Growth of TIL in nodes on tumor surface
      increased 3,000 fold, in ovarian tissues and in tumor proper 2500 and 2000 times
      respectively. The most efficient killing activity was also presented in the
      infiltrating-nodes on tumor surface. CA125 decreased significantly, tumor
      regressed in two patients on follow-up by ultrasound, and ascites disappeared
      completely after one course of chemotherapy and TILs infusion. CONCLUSION: The
      yields of TIL in infiltrating nodes on tumor surface and their efficiency in
      killing activity were higher than those in tumor proper and ovarian tissues, and
      the infiltrating nodes on tumor surface were considered the best sites for
      obtaining specimens.

PMID- 9275431
TI  - [Advances in the study on human chorionic gonadotropin based birth-control
      vaccines].

PMID- 9275432
TI  - [Advances in the research of anti-idiotypic antibody against ovarian cancer].

PMID- 9275433
TI  - [Monitoring of pregnancy induced hypertension].

PMID- 9275434
TI  - [The changes of plasma nitric oxide in patients with pregnancy induced
      hypertension].
AB  - OBJECTIVE: To determine whether the antepartum and postpartum plasma nitric oxide
      (NO) levels were changed in pregnancy induced hypertension (PIH). METHODS: 30
      patients with PIH and 30 healthy women in their late pregnancy were studied. The
      antepartum and postpartum plasma NO2-/NO2- levels, the stable metabolic end
      products of NO, and cyclic guanosine monophosphate (cGMP) were measured with
      greiss reagent. RESULTS: (1) The plasma concentration of NO2-/NO2- and cGMP in
      patients with PIH decreased significantly when compared with that of healthy
      pregnant women (P < 0.01). (2) The concentration of antepartum plasma NO2-/NO2-
      was markedly lower than that of postpartum one in PIH patients (P < 0.01). (3)
      There was a negative correlation between the plasma NO2-/NO3- level and systolic
      blood pressure in PIH (P < 0.01). (4) A positive correlation was seen between
      plasma NO2-/NO3- levels and cGMP levels in PIH patients (P < 0.01). CONCLUSION:
      The decrease of NO synthesis may be one of the important factors responsible for
      PIH.

PMID- 9275435
TI  - [Investigation on the causes of pregnancy induced hypertension].
AB  - OBJECTIVE: To investigate some possible causes of pregnancy induced hypertension
      (PIH). METHODS: Plasma antithrombin (AT-II), fibronectin (Fn), plasminogen
      activator inhibitor (PAI) levels were determined at 26-28, 37-38 gestational
      weeks and 24-72 hours after delivery in 114 pregnant women whose mean arterial
      pressure (MAP) > or = 12 kPa or body weight index > or = 0.24. Women were
      longitudinally followed to observe whether PIH developed and its relation to the
      changes of the above parameters. RESULTS: AT-II level decreased and Fn, PAI
      levels increased significantly in PIH patients (P < 0.01). CONCLUSIONS: The
      endothelial cells damage results in an increase of thromboxane A2 (TXA2),
      decrease of prostaglandin I2 (PGI2), and increase of PAI, Fn, decrease of AT-II,
      as well as the increase of angiotensin II sensitivity. All these changes lead to
      vascular constriction. As the results, renal and uterine placenta blood flow
      decrease, then PIH occurrs.

PMID- 9275436
TI  - [Study on platelet antioxidant enzyme activity and platelet granule membrane
      glycoprotein in patients with pregnancy induced hypertension].
AB  - OBJECTIVE: To evaluate the platelet antioxidant enzyme activity and platelet
      activation degree in patients with pregnancy induced hypertension (PIH). METHODS:
      A monoclonal antibody specific for alpha-granule membrane protein (GMP-140) of
      platelet was used to evaluate the platelet (plt) activation degree in 44 cases
      with PIH and 28 cases of normal pregnant women. Meanwhile, the platelet
      antioxidant enzyme (superoxide dismutase, SOD; catalase, CAT) activity were
      determined. RESULTS: Platelet SOD activity of PIH (22.08 +/- 7.66 U/10(9) plt)
      was markedly lower than that of the controls (26.67 +/- 7.59 U/10(9)plt, P <
      0.01). There was no difference between the CAT activity of PIH and controls (9.26
      +/- 4.53 K/10(12) plt, 8.57 +/- 3.69 K/10(12) plt, P > 0.05). The number of GMP
      140 molecules on platelet surface and serum levels of PIH (2073 +/- 902
      molecules/plt, 4.65 +/- 1.74 molecules/L x 10(-13) were significantly higher than
      those of the normal pregnant women (1319 +/- 716 molecules/plt, 1.69 +/- 0.78
      molecules/L x 10(-12), P < 0.01). Correlation analysis between GMP-140 on
      platelet surface, GMP-140 in the serum and SOD activity of PIH showed definite
      negative correlation (r = -0.601, -0.670 respectively, P < 0.05). CONCLUSIONS:
      The decline of platelet antioxidant enzyme activity (especially SOD) and platelet
      activation could play an important role in the pathophysiological changes in PIH.
      The platelet SOD activity and GMP-140 could be new index of platelet
      hyperactivity.

PMID- 9275437
TI  - [Clinical significance of changes of urinary enzymes in pregnancy induced
      hypertension].
AB  - OBJECTIVE: To study the clinical significance of changes of N-acetyl-beta-D
      glucosaminidase (NAG) and lysozyme in random urine sample in pregnancy induced
      hypertension (PIH). METHODS: The concentration of NAG was measured by
      oronitrophenol spectrophotometric methods, and the concentration of lysozyme by
      agar plate diffusion method. Random urine samples from 266 pregnant women were
      examined, 110 cases were normal pregnant women, 156 cases were PIH patients.
      RESULTS: (1) The level of NAG and lysozyme in moderate and severe PIH patients
      were significantly higher than that in mild PIH patients and normal pregnant
      women (P < 0.01) and it increased with the severity of disease. (2) There was a
      positive correlation between NAG and protein/creatinine (Pr/Cr) ratio in random
      urine. (3) There was a positive correlation between urinary lysozyme and serum
      beta 2-microglobulin (r = 0.874, P < 0.05). CONCLUSION: Determination of urinary
      NAG and lysozyme levels will differentiate various states of PIH.

PMID- 9275438
TI  - [Determination of serum free amino acids and ammonia in pregnant women with
      severe pregnancy induced hypertension].
AB  - OBJECTIVE: To determine the changes of serum free amino acids and ammonia in
      pregnant women with severe pregnancy induced hypertension (PIH) and to evaluate
      its significance. METHODS: 16 kinds of free amino acids and ammonia in maternal
      serum were measured by auto-amino acid-analyzor in 33 cases with severe PIH and
      29 normal pregnancies. Haematocrit (HCT) and hemoglobin (Hb) in some of the
      samples were also determined. The correlation between HCT, Hb and the total free
      amino acid were studied. RESULTS: The group with PIH showed the following
      changes: amino acidemia and ammonemia; high aromatic amino acidemia; high
      threonine, arginine, glycine, cystine and glutamic acidemia. The level of
      glutamic acid was obviously higher in the eclampsia patients than that in the
      preeclampsia ones. There existed a negative correlation between the quantities of
      the total amino acid and HCT and Hb in PIH group. CONCLUSION: There were amino
      acidemia and ammonemia in PIH patients. The high levels of some amino acids might
      be related with the pathogenesis of hypertension and the cerebral symptoms.

PMID- 9275439
TI  - [The clinical value of fetal congenital heart disease diagnosed by color Doppler
      echocardiography].
AB  - OBJECTIVE: To investigate the clinical value of color Doppler echocardiography
      for the diagnosis of fetal congenital heart disease (CHD). METHODS: 368 cases of
      high risk fetuses of CHD, aged from 20-40 gestational weeks, were examined by
      color Doppler echocardiography with Acuson 128 x P/10 color Doppler flow imaging
      system. The prenatal echocardiographic diagnosis were confirmed by fetal autopsy
      and echocardiographic examine after birth as well as follow-up. RESULTS: 11 cases
      of fetal CHD were detected by prenatal echocardiography, of those, 5 cases of CHD
      were confirmed by fetal autopsy after induction of labor and 5 cases of CHD were
      confirmed by color Doppler echocardiography after birth, 1 case of false-positive
      and 1 case of false-negative. CONCLUSIONS: The study suggests that four-chamber
      view is an important view for detecting fetal CHD by echocardiography, but
      multiple views are necessary for diagnosis of fetal complex CHD. Color Doppler
      echocardiography lists as the first choice for prenatal diagnosis of fetal CHD.

PMID- 9275440
TI  - [The relationship between onset of labour and concentration of hyaluronic acid
      and estradiol to progesterone ratio].
AB  - OBJECTIVE: To study the changes of serum hyaluronic acid (HA) level and estradiol
      (E) to progesterone (P) ratio during pregnancy and their relationship with onset
      of labour. METHODS: 116 normal pregnant women with different gestation age and
      different phases in labour and 20 postpartum women were studied with 30 cases of
      nonpregnant women as control. Concentration of HA, E2 and P were determined by
      radioimmunoassay. RESULTS: Serum concentration of E2, P and their ratio increased
      gradually during pregnancy and reached their peaks at the onset of labour. HA
      concentration was similar to nonpregnant women during first and second trimester,
      however, significantly increased during labour, and then decreased rapidly to
      nonpregnant level at 2-3 days postpartum; concentration of HA, E2, P and E2/P
      increased significantly during labour but unrelated to the gestational age when
      labour began; serum concentration of HA was negatively correlated with the latent
      phase (r = -0.344, P < 0.05) but not with the active phase. CONCLUSION: HA, E2, P
      and E2/P may play an important role in the initiation of labour and may be of
      value in evaluating cervical ripening and facilitating labour management.

PMID- 9275441
TI  - [Clinical study on induction of labor with feedback pulsatile oxytocin system].
AB  - OBJECTIVE: To improve the safety and the effect on induction of labor with
      oxytocin. METHOD: 112 cases were selected for labor induction with feedback
      pulsatile oxytocin under the monitoring of uterine contraction controller (study
      group). 112 cases were selected with continuous intravenous infusion of oxytocin
      as a control (control group). The dose of oxytocin and the pulse time-point were
      adjusted. The effects of labor induction in the 2 groups were compared. RESULTS:
      The most suitable time-point was 1.5 minute after the uterine contraction. The
      best administration duration was 20 seconds. But the most suitable dose varied
      individually, generally 12-25 mU. The mean time to establish contraction in study
      group was significantly shorter (1.9 +/- 1.2 min) than that of the control group
      (115.5 +/- 72.3 min, P < 0.001). The average dose of oxytocin administered per
      hour was significantly less in the study group (312 +/- 64 mU) than that of the
      control group (735 +/- 125 mU, P < 0.001) the success rate was 100% in study
      group whereas only 90.2% in control group (P < 0.01). The total duration of labor
      in the study group was 6.9 +/- 4.7 hours in contrast to 20.4 +/- 10.9 hours in
      the control group (P < 0.001). The occurrences of dystocia, postpartum hemorrhage
      and neonatal asphyxia were lower in study group. CONCLUSION: This study proved
      that the administration of oxytocin with the feedback pulsatile oxytocin system
      is easier to establish the effective uterine contraction, and it is a more
      physiologic and effective regimen for induction of labor.

PMID- 9275442
TI  - [The obstetric outcome of in vitro fertilization and embryo transfer pregnancy].
AB  - OBJECTIVE: To evaluate the obstetric outcome of in vitro fertilization and embryo
      transfer (IVF-ET) pregnancy. METHOD: This study compared the obstetric outcomes
      of 20 cases of IVF-ET pregnancy with that of 8210 deliveries at the same period
      in our hospital. RESULTS: There were 45% (9/ 20) preterm birth, 50% (10/20)
      multiple pregnancy, 55% (11/20) pregnancy induced hypertension, 30% (6/20)
      placenta previa and 85% (17/20) cesarean section in group of IVF-ET pregnancy.
      CONCLUSION: The incidences of preterm birth, multiple pregnancy, pregnancy
      induced hypertension or placenta previa were significantly higher in IVF-ET
      pregnancy.

PMID- 9275443
TI  - [Hormonal therapy for the synchronization between donor and recipient in an
      oocyte donation and surrogacy fertilization in vitro-embryo transfer program].
AB  - OBJECTIVE: To evaluate the efficacy of hormonal therapy for the establishment of
      endometrium synchronous with the embryo in an oocyte donation and surrogacy
      fertilization in vitro-embryo transfer (IVF-ET) program. METHODS: The IVF-ET
      routine of the Beijing Medical University was employed. The recipients included
      cases with (1) premature menopause and (2) abnormal chromosomal karyotypes;
      surrogate mothers. For (1) surrogate mother, low constant doses of estradiol (E2)
      (17-beta estradiol-Estrace or E2 valerate) 2-4 mg was started 3-5 days before the
      expected menstruation of the donor progesterone (P) was started intramuscularly
      30 mg daily from the day of hCG injection, 50 mg from the day of oocyte pick-up,
      100 mg from the day of embryo transfer and 150 mg from the day of positive
      urinary beta-hCG; E2 was maintained at the 4 mg dose. Both E2 and P were
      continued until after the luteo-placental shift-about 90 to 100 days of pregnancy
      with gradual tapering doses. The serum E2 and P levels were measured by
      radioimmunoassay and compared with those of normal pregnancy. For (2) women with
      normal menstrual periods, the Chinese made gonadotropin-releasing hormone-A (GnRH
      A) 400-600 micrograms was given for down-regulation of pituitary and artificial
      agonadism when at least amenorrhea of two months was achieved and a quiescent
      state of the endometrium and ovaries was ascertained by vaginal ultrasonography.
      Then the E2 and P therapy was started as described above. GnRH-A was stopped on
      the day of hCG injection. RESULTS: In the hormonal therapy group, the serum E2
      levels were quite similar to those of the normal pregnancy, while the P levels
      were about 3-5 times higher. Two full term deliveries of normal female babies and
      one in her 36th week of pregnancy were achieved in the premature menopause group.
      In the normal menstruation group, one was in her 15th week of pregnancy and the
      surrogate mother was in h34 4 1/2 months of pregnancy. CONCLUSION: The proposed
      hormonal therapy to synchronize the donor and the recipient may be used with
      satisfactory clinical outcome in an oocyte donation and surrogacy IVF-ET program.

PMID- 9275444
TI  - [Single-dose intramuscular methotrexate for treatment of ectopic pregnancy].
AB  - OBJECTIVE: The efficacy and indication of single-dose intramuscular methotrexate
      to treat early ectopic pregnancy were explored. METHODS: 27 cases of ectopic
      pregnancy were treated by single-dose intramuscular methotrexate (50 mg/m2)
      without citrovorum rescue. The beta-hCG was monitored regularly till it became
      normal. Twelve of them recieved this regimen in outpatient service. RESULTS: 24
      cases (88.9%) were successfully treated. Three failed and switched to operation.
      There were no significant differences (P > 0.05) in gestational age and size of
      adnexa ectopic mass between successful cases and failed cases, but highly
      significant differences (P < 0.01) in occurrence rate of abdominal pain and beta
      hCG titers before treatment. CONCLUSION: The early diagnosis and adherence to
      strict criteria are the keys to successful management. No abdominal pain, ectopic
      mass < or = 5 cm in greatest dimension and titer of serum beta-hCG < 6000 IU/L
      were mainly indications of drug treatment.

PMID- 9275446
TI  - [Antiphospholipid antibodies and antiphospholipid syndrome and their relation
      with preqnancy-induced hypertension].

PMID- 9275445
TI  - [Serological analysis of antibodies by anti-idiotypic monoclonal antibody 6B11
      against ovarian carcinoma].
AB  - OBJECTIVE: To establish a method for detection of serologic antibody by anti
      idiotypic monoclonal antibody 6B11 against ovarian carcinoma. METHOD: Sera
      antibody exminations from 172 cases, malignant and benign ovarian and uterine
      tumors as well as normal individuals as control were done respectively. 15 cases
      of ovarian epithelial carcinoma with 133 blood samples were examined serially by
      enzyme linked immunoabsorbent assay during the first 12 month after treatment.
      RESULTS: The cutoff value was determined and calculated from sera of normal
      controls. The positivity of epithelial ovarian carcinoma was 67.3%, much higher
      than that in the benign ovarian tumor and malignant or benign uterine tumors with
      statistical significant difference. The serial examinations of the sera in 15
      cases of ovarian epithelial carcinoma showed that the negative result turned from
      the positive one was corresponding with disease status. CONCLUSIONS: The
      examination of sera-antibody tested by anti-idiotypic monoclonal antibody 6B11
      may give a help for the diagnosis of ovarian carcinoma and may be used as one of
      the tumor markers for follow up.

PMID- 9275447
TI  - [Modern veiws on pathological classification, therapy and the factors affecting
      prognosis in endometrial cancer].

PMID- 9275448
TI  - [Current status in the diagnosis and treatment of endometriosis].

PMID- 9275449
TI  - [Histologic examination and immunohistochemical analysis of estrogen and
      progesterone receptors of eutopic and ectopic endometrium in patients with
      endometriosis].
AB  - OBJECTIVE: To study the differences of histologic dating and steroid receptors
      between ectopic and eutopic endometrium in patients with endometriosis. METHODS:
      Histologic examinations were done on eutopic and ectopic endometrium in 28
      patients with pelvic endometriosis, and estrogen and progestrone receptors
      concentrations were determined by immunochemical ABC method in 15 patients. All
      the ectopic tissues were biopsied from peritoneal lesions. RESULTS: In 67.9%
      patients, the ectopic endometrium development was retardated and 14.3%
      accelerated as compared with eutopic endometrium, and only 17.9% identical. The
      estrogen receptors (ER) and progesterone receptors (PR) contents of ectopic
      endometrium were significantly lower than those of eutopic endometrium in
      glandular cells (P < 0.01, P < 0.05 respectively), while differences were not
      significant in stroma cells. CONCLUSIONS: The advantage of the immunochemical
      technique is that it can definitely locate the site of receptors in the
      histologic section. The difference in histologic dating and ER and PR
      concentrations in the eutopic and ectopic endometrium may be accounted for by the
      different steroid environments and pathogenic theory of peritoneum metaplasia.

PMID- 9275450
TI  - [The measurement of natural killer cell activity in peripheral blood and
      peritoneal fluid of patients with endometriosis].
AB  - OBJECTIVE: To investigate the role of natural killer (NK) cell activity in the
      development of endometriosis. METHODS: The NK cell activity in peripheral blood
      (PB) and in peritoneal fluid (PF) of 72 patients with endometriosis was studied
      by means of MTT-assay and compared with that of infertile women and fertile
      controls. RESULTS: The NK cell activity in PB and in PF of patients with
      endometriosis was lower than that in those of infertile and fertile controls, and
      decreased as the stage of endometriosis increased. Follow-up of 8 patients with
      stage II/N endometriosis demonstrated that the NK cell activity in PB had a
      moderate increase shortly after excision of endometriotic lesions, but decreased
      again to the preoperative level 6-9 months later. CONCLUSIONS: Patients with
      endometriosis have a primary defect in their NK cell function, and the defect may
      be related to the pathogenesis of the disease.

PMID- 9275451
TI  - [The value of serum CA125 assays in the diagnosis of uterine adenomyosis].
AB  - OBJECTIVE: To investigate the value of serum CA125 assays in the diagnosis of
      uterine adenomyosis. METHODS: Fifty-five consecutive patients with uterine
      adenomyosis and twenty with leiomyoma of uterus, diagnosed by surgery and
      pathology were studied. The blood samples were taken one day before operation.
      Twenty normal healthy women were served as controls. CA125 levels were determined
      by radioimmunoassay method. RESULTS: The median (M) CA125 levels (Ql-Qu) for
      patients with adenomyosis, leiomyoma and normal controls were 102.1 (56.3
      182.1)kU/L, 34.6 (33.7-43.8)kU/L and 33.1 (32.7-33.8)kU/L respectively. The
      differences among the three groups were all significant (P < 0.01). The CA125
      positive rates (CA125 > 50kU/L) for the above three groups were 80.0%, 10.0% and
      5.0% respectively. Patients with adenomyosis had a higher CA125 positive rate
      than those with leiomyoma or normal controls (P < 0.001). For patients with
      adenomyosis the CA125 levels were positively correlated with uterine size (r =
      0.33, P < 0.05). The adenomyosis patients treating with sex hormone preparations
      were found to have lower CA125 levels in comparison with non-users (P < 0.05).
      The mean CA125 level measured in sixteen patients decreased significantly one
      week postoperation. CONCLUSIONS: Serum CA125 assay is of great assistance to the
      diagnosis of uterine adenomyosis as well as to the differential diagnosis between
      adenomyosis and leiomyoma of uterus.

PMID- 9275452
TI  - [The changes in plasma nitric oxide level in normal pregnant women and pregnancy
      induced hypertension].
AB  - OBJECTIVE: To investigate the relationship between nitric oxide (NO) level and
      pregnancy induced hypertension (PIH). METHODS: The plasma level of NO in 36 cases
      of normal pregnant women (normal pregnancy group), 23 cases of PIH (PIH group),
      and 16 cases of non-pregnant women (control group) were measured and compared
      using fluorophotometry. RESULTS: The NO level of normal pregnancy group was
      significantly higher than that of control group (P < 0.01), particularly in the
      second trimester of pregnancy. The NO level of PIH was significantly lower than
      that of third trimester of normal pregnancy (P < 0.01), and it decreased as the
      disease became severe. CONCLUSIONS: Decreased synthesizing and releasing of NO
      might play an important role in pathogenesis of PIH.

PMID- 9275453
TI  - [The preliminary study on the hepatitis B virus infection rate of peripheral
      blood mononuclear cell in both HBsAg and HBeAg-positive pregnant women and its
      role in intrauterine transmission].
AB  - OBJECTIVE: To study the hepatitis B virus (HBV) infection rate of peripheral
      blood mononuclear cells (PBMC) and the role of infected PBMC in the intrauterine
      transmission. METHODS: Polymerase chain reaction (PCR) was using for detection of
      HBV-DNA in PBMC of 52 both HBsAg and HBeAg positive pregnant women just before
      onset of labour, and HBsAg were detected in sera of their neonates by enzyme
      linked immunoabsorbent assay (ELISA) within 24 hours after birth. RESULTS: HBV
      infection rate of PBMC in these women was 46.2% (24/52). There was positive
      correlation between infection rate of PBMC and HBsAg titre of pregnant women (chi
      2 = 4.59, P < 0.05), but no relationship between PBMC infection rate and neonatal
      HBV infection. CONCLUSION: The possibility of intrauterine transmission of HBV by
      infected PBMC through transplacental passage was small.

PMID- 9275454
TI  - [Hemoglobin A1c in diabetes related to pregnancy induced hypertension].
AB  - OBJECTIVE: To test the hypothesis that the poor control of diabetes during
      pregnancy is correlated with a high rate of pregnancy induced hypertension (PIH).
      METHODS: A retrospective analysis on 146 pregnant women with diabetes mellitus of
      White's class B to RF (gestational diabetes was excluded) diagnosed before
      pregnancy was carried out in Yale-New Haven hospital, U.S.A. RESULTS: 36.3% of
      the diabetic women developed PIH. Hemoglobin A1c (HbA1c) levels were higher than
      normal in 63.7% (93 cases) of the patients during their initial prenatal visits.
      In the group with HbA1c score > or = 6 and White's Class D-RF, more cases
      developed PIH than that in groups with HbA1c score < 6 and White's Class B and C
      (P < 0.01, P < 0.05). CONCLUSION: Diabetic women with high HbA1c score or
      advanced White's Class during pregnancy were at increased risk for PIH. Good
      control of blood glucose level throughout pregnancy may reduce the risk of PIH in
      diabetic women.

PMID- 9275455
TI  - [Determinations of antiovarian antibodies and cellular immunity functions in
      patients with premature ovarian failure].
AB  - OBJECTIVE: To investigate the variations of cellular immunity function and its
      relationship with antiovarian antibodies (AOAb) in patients with premature
      ovarian failure (POF). METHODS: Serum AOAb, T-lymphocyte subsets and
      leukocyteprocoagulant activity (LPCA) to ovarian antigens of peripheral blood
      were examined in 30 normal women (control group) and 30 patients with POF (POF
      group). RESULTS: The mean serum AOAb level in POF group was significantly higher
      than that in control group (6.80 +/- 1.9 kU/L vs 1.39 +/- 0.72 kU/L, P < 0.01).
      The percentage of CD3+, CD4+ cells increased significantly (65.42 +/- 5.31% and
      44.79 +/- 5.90%, respectively), the percentage of CD8- cells was significantly
      lower (25.63 +/- 4.26%) and the ratio of CD4+/CD8+ increased (1.66 +/- 0.27) in
      POF group when compared with control group (P < 0.01). The positive rate of AOAb
      in patients who had elevated ratio of CD4+/CD8+ was significantly higher than
      those with normal CD4+/CD8+ ratio (85.7%, 18/21 vs 3/9; P < 0.01). The level of
      LPCA was elevated in POF patients with positive AOAb, and was correlated
      positively with the level of AOAb (chi 2 = 8.378, P < 0.01). CONCLUSIONS: These
      data showed that cellular immunity and humoral immunity to ovarian antigens can
      be concurrently produced in POF patients, and suggested that pathogenesis of POF
      may be associated with immune factors.

PMID- 9275456
TI  - [Effects of clomiphene citrate treatment on endometrial estrogen and progesterone
      receptors expressions].
AB  - OBJECTIVE: To assess the effects of clomiphene citrate (CC) on estrogen receptors
      (ER) and progesterone receptors (PR) expressions in glandular, epithelial and
      stromal cells of endometrium. METHODS: Endometrium samples of 16 normal ovulatory
      women (11 with unexplained and 5 female infertility) were taken in the late
      proliferative phase (12th day) and late secretory phase (10 days after
      ovulation), both in spontaneous and CC-induced cycles. ER and PR in glandular,
      epithelial and stromal cells of endometrium were localized and their histological
      score (H-score) were measured semi-quantitatively by monoclonal antibodies
      immunohistochemical analysis. RESULTS: The H-score of ER and PR contents were
      significantly lower in late proliferative phase and secretory phase of CC cycles
      when compared with that in spontaneous cycles (P < 0.01, P < 0.05). The decrease
      of receptor contents in glandular cells was significantly pronounced than that in
      stromal cells (P < 0.05). In late proliferative phase the decrease of ER was
      significantly severe than that of PR. On the contrary in late secretory phase the
      decline of PR was more significant. CONCLUSIONS: Based on these data, we
      suggested that CC inhibited the ER and PR induction in endometrium and affected
      endometrial development. These may be one of the causes of low pregnancy rate in
      CC-induced cycles.

PMID- 9275457
TI  - [The effect of mifepristone on progesterone and estrogen receptors in human
      decidua and serum hormone levels].
AB  - OBJECTIVE: To examine the effects of mifepristone on progesterone and estrogen
      receptors in human decidua and steroid hormone levels in serum for investigating
      the mechanisms of antigestational action of mifepristone. METHODS: Decidual
      progesterone receptor (PR) and estrogen receptor (ER) concentrations or binding
      sites were measured by both dextran coated charcoal (DCC) and histochemical
      methods in normal subjects and after 100 mg-mifepristone treatment. Meanwhile,
      the concentrations of serum beta-human chorionic gonadotropin (beta-hCG),
      estradiol (E2), progesterone (P) and testosterone (T) were also determined by
      radioimmunoassay. The reactions of these two groups were compared. RESULTS:
      Mifepristone therapy significantly reduced decidual cytosol PR content (P < 0.05)
      and increased decidual cytosol ER content (P < 0.05). Histochemical analyses
      indicated mifepristone treatment increased ER staining in vessel and glandular
      cells of decidua. The serum beta-hCG, E2 and T levels elevated significantly
      after mifepristone administration, while the progesterone levels were unaffected.
      CONCLUSION: Our data suggested that the anti-gestational effect of mifepristone
      may act through decreasing the decidual PR and increasing the ER concentrations,
      which interfered the balance between these two components, and also through
      increasing serum T levels.

PMID- 9275458
TI  - [Occurrence of depression symptoms and their influence factors in perimenopausal
      women].
AB  - OBJECTIVE: To investigate the prevalence of depression symptoms and their
      influence factors in perimenopausal women. METHODS: Self-rating depression scale
      and general condition questionaire were used in 419 perimenopausal women aged 45
      55 in Beijing city. RESULTS: The prevalence of depression symptoms in these women
      was 46.1%, among which 69.9% was mild and 30.1% moderate or severe. The
      occurrence of depression symptoms in worker group was higher than cadres or
      skilled person groups (P < 0.01). The incidence of depression symptoms in women
      with systemic diseases was higher than those without (P < 0.001). Women with
      decreased libido and dissatisfaction with their husbands, family income and
      living conditions had a higher incidence than those without (P < 0.05).
      CONCLUSIONS: The prevalence of depression symptoms in perimenopausal women was
      considerably high. Clinical doctors should pay attention to psychological
      problems especially for women with high risks during medical treatment.

PMID- 9275459
TI  - [Management and prognosis of advanced ovarian cancer associated with bowel
      metastasis and obstruction].
AB  - OBJECTIVE: To investigate the high risk factors and prognostic factors of bowel
      metastasis and obstruction in the patients with late stage ovarian cancer by
      analyzing the clinical characteristics and to find out appropriate methods to
      solve this difficult problem. METHODS: 151 cases with ovarian cancer in stages I
      and IV who received the treatment from January 1, 1988 to December 31, 1992 were
      analyzed retrospectively. RESULTS: Operative residues, diffuse bowel metastasis,
      small intestinal involvement and papillary serous cystadenocarcinoma were found
      to be high risk factors for bowel obstruction. Age, duration between operation
      and obstruction, level of CA125 at occurrence of obstruction, numbers of
      operation and the histologic grade were disclosed as prognostic factors. The
      prognosis was much worse if the score is more than 6. CONCLUSION: Due attention
      paid to the high risk factors and the prognostic factors should be emphasized to
      improve the quality of life and the survival rate.

PMID- 9275460
TI  - [Cytoreductive surgery plus combined chemotherapy for the treatment of advanced
      ovarian cancer].
AB  - OBJECTIVE: To evaluate the impact of cytoreductive surgery plus combined
      chemotherapy on advanced ovarian cancer. METHODS: From Jan. 1980 to Dec. 1992, 76
      patients admitted to our hospital for primary treatment, were eligible for
      retrospective evaluation. 26 patients with stage II and 50 with stage II. All
      patients with ovarian cancer were given cytoreductive surgery followed by
      systemic and intraabdominal chemotherapy. Regimens were CAP (Cyclophosphamide,
      Adriamycin, Cisplatin), AP (Adriamycin, cisplatin) or CE (Carboplatin, Epi
      adriamycin). RESULTS: In 52 patients no residual tumor was found in 24 patients
      there were residual lesions less than 2cm in diameter. Postoperative chemotherapy
      ranged from 1 to 12 courses. The overall 5-year-survival rate was 33.6%, with
      34.9% for stage II and 29.5% for stage II (P > 0.1). The 5-year-survival rates of
      cases with and without residual tumor were 16.5% and 37.6% respectively, the
      rates of those cases receiving less or more than 8 courses of chemotherapy were
      20.0% and 60.1% respectively. CONCLUSION: The prognosis of ovarian cancer
      following cytoreductive surgery is influenced by residual tumor, and the number
      of courses of chemotherapy.

PMID- 9275462
TI  - [Estrogen and progesterone receptors and growth factors in patients with
      endometriosis].

PMID- 9275461
TI  - [Treatment of uterine leiomyoma by two different doses of mifepristone].
AB  - OBJECTIVE: To study the response of uterine leiomyoma to two different daily
      dosages of mifepristone. METHODS: Prospective nonrandomized clinical trial on
      women with symptomatic uterine leiomyoma was conducted. Twenty-eight patients
      were treated with 10mg of mifepristone daily and fifteen patients with 20mg daily
      for 12 weeks, beginning on day 1 to 3 of the menstrual cycle. Volume changes of
      leiomyoma and uterus were measured with ultrasonography before treatment (as
      baseline) and monthly during the course of therapy. Blood samples for hemoglobin,
      liver and renal function were obtained monthly. RESULTS: Ovarian acyclicity was
      induced in both groups of patients given different daily doses of mifepristone
      and dysmenorrhea and low abdominal pain disappeared. All symptoms and signs of
      anemia were resolved. The average hemoglobin level elevated 14-16g/L monthly.
      After 12 weeks of mifepristone treatment, the leiomyoma volume decreased to 41.4%
      of baseline in the 10mg daily dose group and 43.0% in the 20mg daily dose group.
      There was no significant difference between the two treatment groups; the side
      effects were similar. CONCLUSION: Mifepristone of 10mg daily is considered to be
      a more ideal dosage for treatment. Mifepristone therapy is indicated in larger
      fibroids, and/or as preoperative medication for severely anemic patients and in
      perimenopausal patients with symptomatic fibroids.

PMID- 9275463
TI  - [Gestational diabetes].

PMID- 9275464
TI  - [A prospective for the study of nitric oxide].

PMID- 9275465
TI  - [Nitric oxide in the treatment of pulmonary artery hypertension induced by
      chronic obstructive pulmonary diseases].

PMID- 9275466
TI  - [Measurement of NOS activity by monitoring the conversion of 3H-arginine].
AB  - OBJECTIVE: To establish a method for measuring the constitutive and inducible
      nitric oxide synthase (NOS) through the conversion of L-3H arginine to L-3H
      citrulline. METHODS: NOS extracted from cerebellar of porcine and rat was
      purificated through DEAE cellulose or/and 2', 5', -ADP agarose. NOS activity was
      assayed by monitoring the conversion of 3H-arginine to 3H-citrulline. RESULTS: A
      4,460 fold purification of the porcine cerebellar NOS was obtained with an
      activity of 669 pmol mg-1 min-1 and a 2.7% recovery. For purification of rat
      cerebellar NOS, affinity chromatography with 2', 5'-ADP agarose column provided a
      2646 fold purification of enzyme activity with a 688 pmol.ml-1.min-1 and 27%
      recovery. The purified rat and porcine cerebellar NOS constituted a single band
      on SDS/PAGE at about 160,000. CONCLUSION: A stable and special method for
      measuring NOS activity was established.

PMID- 9275467
TI  - [L-arginine nitric oxide pathway in acute renal ischemia reperfusion injury of
      the aged rats].
AB  - OBJECTIVE: To gain further insights into the greater susceptibility to acute
      ischemic renal injury (ARF, 45 minutes of renal arteries clamping) of old rats
      (O, 24-26 months) as against young ones (Y, 3-4 months), and the possible role of
      endothelium derived relaxing factor (EDRF) and its influence on ischemic renal
      function. METHODS: Basal renal dynamics was compared between O and Y. RESULTS:
      Two hours after ischemia, the decrease of GFR RPF, and UV was more severe in O
      than in Y. Urine cGMP was significantly dropped in both groups. Intravenous
      administration of L-arginine increasld urine cGMP of the O as well as the Y, with
      that of the Y higher than that in O. GFR, RPF, UV were elevated significantly in
      the O. Simultaneous administration of L-NNA, the analogue of L-Arginine could
      partially antagonize its effect on elevating RPF. RT-PCR technique was used to
      detect renal inducible nitric oxide synthase (iNOS) expression. Although the
      ischemic kidney was capable of expressing iNOS mRNA in the presence of L-arginine
      after ischemia, the production of NO in the old may not be regulated at the
      transcriptional level, other factors such as NOS enzyme activity, availability of
      L-arginine and O2, metabolism of NO after its production were suspected to be
      involved.

PMID- 9275468
TI  - [Gene diagnosis for hepatolenticular degeneration by genetic linkage analysis
      with four short tandem repeat polymorphisms].
AB  - OBJECTIVE: To study the clinical application value of genetic linkage analysis
      for hepatolenticular degenaration (Wilson's disease, WD) with four STR--D13S316,
      D13S133, D13S301, and D13S314. METHODS: Polymorphisms of the four short STR, of
      which one (D13S301) was located in WD gene and the other three (D13S316, D13S133
      and D13S314) were at flanking sites of the gene, were amplified by polymerase
      chain reaction, and the alleles indentification was performed with denaturing
      polyacrylamide gel electrophoresis and used as genetic marker for haplotype
      analysis. RESULTS: Genetic linkage analysis indicated that among 56 individuals
      (35 siblings and 21 secondary-relatives) without any clinical symptoms, 26 were
      WD heterozygotes, 2 presymptomatic and 28 normal. Among three patient previously
      diagnosed as possible WD patients, one was identified as WD heterozygote and the
      other two WD patients definitely. CONCLUSION: This genetic diagnosis system based
      on the four STR polymorphisms is of high clinical application value for
      distinguishing individuals from WD families.

PMID- 9275469
TI  - [The effect of local hyperthermia on NK activity and lung metastasis in mice].
AB  - OBJECTIVE: To study the effects of local hyperthermia on primary and metastatic
      focus. METHOD: Animal tumor model was established in C57BL/6 mouse by injecting 5
      x 10(5) Lewis lung carcinoma cells into the left foot pad. Ten days later, a
      tumor mass of 10 x 10 mm was seen, and local hyperthermia was performed at 37,
      43, 45 and 47 degrees C for 30 minutes with water bath. 96 mice were randomly
      divided into four groups of 1, 2, 3, 4 weeks according to time of sacrifice.
      Every group had 6 mice. RESULTS: NK activity increased after 43-45 degrees C
      hyperthermia, and was higher than that of the control group (37 degrees C). The
      growth rate and lung metastasis decreased. CONCLUSION: Host immunity is thought
      to be enhanced by local hyperthermia and plays an important role in eradicating
      primary tumor and controlling distant metastasis.

PMID- 9275470
TI  - [Establishment of anti-HCV NS5 alpha McAb hybridoma cell lines and its
      application on clinical immunohistochemical diagnosis].
AB  - OBJECTIVE: To prepare hybridoma cell lines which secrete anti-HCV recombinant
      NS5a protein monoclonal antibodies, and to evaluate their usage in investigating
      the distribution of HCV NS5a antigen in liver tissue. METHODS: The hybridoma cell
      lines were raised using the conventional protocols. The immunohistochemistry of
      paraffin embedded liver tissue was performed to determine the distribution of HCV
      NS5a antigen as well as NS3 antigen in liver tissue. RESULTS: Four hybridoma cell
      lines, which secrete monoclonal antibodies against HCV NS5a protein, were raised
      and named as 8B2, 6F11, 4C6 and 7D9. They had specific reaction with HCV NS5a
      protein and had no reaction with HCV core and NS3 proteins. Immunohistochemistry
      results indicated that 54.8% of anti-HCV positive patient's liver specimens were
      positive and 70.6% of active cirrhosis positive. CONCLUSION: The monoclonal
      antibodies we prepared here are specific to the recombinant HCV NS5 alpha protein
      and they can be used in the clinical immunohistochemistry diagnosis.

PMID- 9275471
TI  - [Analysis of telomere restriction fragments in human astrocytomas and
      glioblastomas].
AB  - OBJECTIVES: To analyse the length of telomere restriction fragments (TRF) in
      different type of human astrocytomas as well as normal brain tissues and to
      evaluate the correlation of telomere status and tumor progression. METHODS: DNAs
      extracted from normal and tumor samples were studied with Southern blot analysis,
      using (TTAGGG)4 probe specific for human telomeric sequences. RESULTS: The lower
      portion of TRFs of astrocytoma type I, II and III was shortened gradually in
      comparison with that of normal brain tissues: both uper and lower portions of
      TRFs in 12 cases of glioblastoma multiformes studied were lost distinctively.
      However, no obvious length difference of TRFs could be detected between primary
      and recurrent glioblastomas. CONCLUSIONS: Telomere reduction is one of the
      important genetic events during transformation of astrocytomas. Telomere repair
      mechanism may be initiated in glioblastoma cells which may, therefore, maintain a
      relative stabitity of TRFs and permit a constitutive proliferation of those
      malignant cells.

PMID- 9275473
TI  - [The role of urokinase type plasminogen activator in invasion of bile duct
      carcinoma].
AB  - OBJECTIVE: To study the role of urokinase type plasminogen activator (u-PA) in
      the invasive process of bile duct carcinoma. METHODS: The secretion of u-PA and
      the invasive potential of tumor cell in vitro in a newly established cell line of
      bile duct carcinoma, QBC939, were observed by using an amnion invasion culture
      system. RESULTS: QBC939 cells secreted u-PA with high invasive potential. The
      inhibitors of u-PA and plasmin, tranexamic acid and 6-aminocaproic acid,
      obviously inhibited the u-PA activity and the invasive potential of QBC939 cells.
      CONCLUSION: u-PA is one of the important enzymes in tumor invasion. Inhibiting u
      PA or plasmin may be a prospective therapy for tumor treatment.

PMID- 9275472
TI  - [The variation in motility, adhesion of mouse lung adenocarcinoma variants with
      low and high metastatic potential under the action of laminin (LN): a comparative
      study].
AB  - OBJECTIVE: To compare the variation in morphology of low and high metastatic
      variants C6 and C7, which were isolated from mouse lung adenocarcinoma cell line
      (LA795) by single cell culture technique. METHOD: The low and high metastatic
      variants C6 and C7 were used in vitro, to compare the variation in morphology,
      cytoskeleton, motility, adhesion under the action of LN molecule and to compare
      the variation in the expression of endogenous LN molecule as well. RESULTS: Under
      LN molecule free culture condition, the motility and adhesion of high metastatic
      cell C6 were lower than those of low metastatic cells C7. This phenomenon
      indicated that the metastatic potential in vivo might be of negative correlation
      to the motility or adhesion in vitro. But if the LN molecules were added to the
      culture for 48 hours. Significantly, the motility and the adhesion were enhanced,
      the cytoskeleton network was reorganized, and the morphology was changed. In the
      C6 and C7 cells, both the motility and adhesion in vitro were positively
      correlated with the metastatic potential in vivo under the action of LN molecule.
      In addition, the distribution of the cytoskeleton network in the high metastatic
      variant C6 was uneven, irregular, close to one side of cell nucleus. The high
      metastatic cells C6 were shown strongly positive for endogenous LN by
      immunohistochemical technique and the distribution of the endogenous LN was close
      to one side of the cell nucleus. CONCLUSIONS: The quantity and distribution of
      endogenous and exogenous LN molecule and its receptors on the tumor cells may be
      an important factor for tumor metastatic heterogeneity. The mechanism of the
      action of LN molecule is correlated with the reorganization of the cytoskeleton.

PMID- 9275474
TI  - [Reconstitution of Hu-SCID mice transplanted with human tonsillar lymphocytes
      immunized with dengue virus-2 in vitro and its immune response].
AB  - OBJECTIVE: To study the measure for the reconstitution of severe combined
      immunodeficient disease mice (SCID mice) transplanted with human lymphocytes
      immunized with specific antigen in vitro. METHODS: Hu-SCID mice were constructed
      by intraperitoneal (i.p.) transfer of human tonsillar lymphocytes (TLC) first
      immunized with dengue virus-2 (DV2) in vitro, then boostered with different doses
      of DV2 antigen in vivo. RESULTS: Human immunoglobulin (Ig) and specific human
      anti-DV2 antibodies could be detected in sera of the hu-SCID mice by ELISA. Two
      weeks after transplantion of the in vitro-immunized hu-TLC, the highest human IgG
      concentration was 412.86 micrograms/ml, two or four weeks later specific human
      anti-DV2 IgM or IgG and the neutralizing antibody could found in these sera,
      respectively, the highest titer was 1:6400. The levels of human IgG and human
      anti-DV2 antibodies were related to the dose of DV2 antigen. The presence of
      human B cells (CD20+) and T/cells (CD3+, CD4+, CD8+) were shown in the sleen,
      lung, intestine and mesentery of the hu-SCID mice as determined by
      immunoperoxidase staining, and the cells were distributed correspondingly with
      the lymphocyte cells in proper human tissue. Human anti-DV2 IgG could also be
      detected in the spleen cell culture obtained from the SCID mice. CONCLUSION: By
      co-immunized in vitro and in vivo the SCID mice deduced stronger immune response
      for specific antigen, and the reconstitution of the human lymphocytes could be
      established successfully.

PMID- 9275475
TI  - [Study of immunoregulation by interleukin-1 receptor antagonist in NZB/W F1
      mice].
AB  - OBJECTIVE: It is known that the development of systemic lupus erythematosus (SLE)
      is associated with the highly activated B cells. Interleukin-1 (IL-1) can
      obviously promote the proliferation and secretive activity of B cells. Moreover,
      interleukin-1 receptor antagonist (IL-1ra) can block the effect of IL-1 by
      specifically combining with IL-1 receptor, we, therefore studied the
      immunoregulative action of IL-1ra in lupus-like NzB/w F1 mice to detect any
      possible way to prevent lupus nephritis. METHODS: 12 femal NZB/W F1 mice of 13
      weeks (Weight: 30-35 g) were divided randomly into 2 groups. Each mouse in the
      treated group was intraperitoneally injected with IL-1ra once per 2 weeks for 3
      times by the dosage of 100 micrograms (0.1 ml) per time, while in the control
      group injected with 0.1 ml normal saline. All the mice were killed at the age of
      9 months and the immunologic function was detected. RESULTS: This dosage could
      not prevent absolutely the development of lupus nephritis, but the renal damage
      was alleviated and the urine protein decreased. Moreover, it could improve the
      immunofunction by significantly reducing the levels of serum IL-1 alpha and
      obviously increasing the activities of NK cells and IL-2 induced by ConA in
      mononuclear cells of spleen. There was no significant difference on the levels of
      serum IL-6 and TNF-alpha between the treated group and control group. CONCLUSION:
      IL-1ra has certain regulatory effect on the immunologic function of lupus-like
      NZB/W F1 mice.

PMID- 9275476
TI  - [Systemic inflammatory response syndrome].

PMID- 9275477
TI  - [Advances in the research on pathogenic mechanism of chronic hepatitis B].

PMID- 9275478
TI  - [Strengthen the study on the relation between cytokines and glomerulosclerosis].

PMID- 9275479
TI  - [Heighten the awareness of antineutrophil cytoplasmic autoantibody-related
      systemic small vessel angiitis].

PMID- 9275480
TI  - [Inhibitory effect of interleukin-10 on inflammatory reaction in rat mesangial
      cells].
AB  - OBJECTIVE: To investigate the inhibitory effect of IL-10 on inflammatory reaction
      in rat mesangial cells (rMC). METHODS: Cell proliferation was tested by 3H
      thymidine uptake and absolute cell counts. The production of IL-1 and TNF alpha
      by rMC was assessed by bioactivity assay and their gene expression by Northern
      blot hybridization. The expression of intercellular adhesion molecule-1 (ICAM-1)
      on rMC was determined by ELISA. RESULTS: IL-10 (25 ng/ml) inhibited 5% FCS and IL
      1 induced cell proliferation by 39% and 52% respectively. It also suppressed the
      production of IL-1 and TNF alpha bioactivity by rMC by 48% and 68%, which was
      consistent with the decline of IL-1 and TNF alpha gene expression. The IL-1
      induced expression of ICAM-1 on surface of rMC was attenuated by IL-10 treatment.
      CONCLUSION: Our data suggest that IL-10 may be an inhibitory cytokine in
      regulation of inflammatory reaction in glomerular mesangial cells.

PMID- 9275481
TI  - [Immune-mediated tubulointerstitial injury in hemorrhagic fever with renal
      syndrome].
AB  - OBJECTIVE: To study the presence of Hantan virus RNA and specific immune-complex
      deposits in the renal tubular epithelium of HFRS patients. METHODS: Renal biopsy
      specimens from 15 cases of HFRS, 3 cases of ischemic ATN and 5 normal controls
      (donor of transplantation) were investigated. Human HLA-DR, ICAM-ILFA-1 and CD4+,
      CD8+, CD8+ cells in the renal tissue section were quatitatively analyzed by
      immuno-peroxidase staining 4 layers PAP. Histo-morphometric analysis of
      pathological section was made for each specimen. RESULTS: HFRS presented abundant
      amount of HLA-DR and ICAM-1 in tubular cells both on cortical and medullary
      region, while ischemic ATN tended to have such positive results only in cells of
      cortical region. The intensity and extent of HLA-DR and ICAM-1 LFA-1 staining
      were closely correlated with the degree of tubulointerstitial damage of HFRS.
      Interstitial CD4, CD8 and monocytes increased in amount profoundly in HFRS with a
      preponderance in the medullary region, and particularly of CD8 positive cells.
      Less marked increment occurred in ATN cases, and no discrepancies were found
      between cortical and medullary region or cell types. The severity of
      tubulointerstitial lesion was closely associated with the extent of cellular
      infiltration and the expression of HLA-DR, ICAM-1 in renal tubular cells.
      CONCLUSION: The characteristic changes of tubulointerstitial lesions in HFRS
      suggest that virus infection may be one of the mediators responsible for the
      immune kidney injuries in HFRS.

PMID- 9275482
TI  - [Regulative effects of cytokines on the expression of cell adhesion molecules on
      human mesangial cells].
AB  - OBJECTIVE: To study the regulative effects of rhIL-1 beta or rhTNF-alpha on the
      expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell
      adhesion molecule-1 (VCAM-1) on human mesangial cells (HMC). METHODS: At the 4th,
      8th, 16th and 32nd hours after stimulation by rhIL-1 beta (25 ng/ml) or rhTNF
      alpha (100 ng/ml), the mRNA expression of ICAM-1 and VCAM-1 on HMC was determined
      with Northern blot, and their protein expression was also tested with cell ELISA
      analysis. RESULTS: mRNA and protein of both ICAM-1 and VCAM-1 were only basically
      expressed on HMC at very low levels in the control groups without stimulation.
      After stimulation by rhIL-1 beta or rhTNF alpha, however, their expression was
      markedly upregulated. The maximal mRNA expression level of ICAM-1 stimulated by
      rhTNF alpha was present at the 8th hour, but in the remaining groups the maximal
      mRNA expression levels of ICAM-1 or VCAM-1 were all present at the 4th hour.
      Compared with control groups, ICAM-1 protein expression was significantly
      increased from the 4th hour after rhIL-1 beta stimulation (P < 0.05), but in the
      remaining groups ICAM-1 or VCAM-1 protein expression was significantly raised
      from the 8th hour after stimulation (P < 0.001). CONCLUSION: These results
      suggest that upregulated expression of ICAM-1 and VCAM-1 by inflammatory
      cytokines IL-1 beta and TNF alpha may play a pathogenic role in
      glomerulonephritis.

PMID- 9275483
TI  - [Expression of IL-8 mRNA in glomerular endothelial cells].
AB  - OBJECTIVE: To study the expression of IL-8 mRNA in cultured human glomerular
      endothelial cells. METHOD: The effects of IL-1 beta and TNF alpha on the
      production of IL-8 by glomerular endothelial cells were also observed. RT-PCR was
      used. RESULTS: There was only weak expression of IL-8 mRNA in cultured human
      glomerular endothelial cells without the presence of any stimulating factors,
      whereas the expression of IL-8 mRNA in cultured human glomerular endothelial
      cells was significantly increased after the glomerular endothelial cells have
      been treated with IL-1 beta (25 u/ml) or TNF alpha (10 ng/ml) for 24 hours.
      CONCLUSION: Glomerular endothelial cell injury may enhance the expression of IL
      8, which mediates the inflammatory reactions in glomeruli.

PMID- 9275484
TI  - [Role of area postrema on DOCA-salt induced hypertension in rat].
AB  - OBJECTIVE: To determine the effect of area postrema AP on DOCA-salt induced
      hypertension in rat, with emphasis on renal hemodynamics. METHOD: Blood pressure,
      salt and water balances and renal hemodynamics were observed in AP ablated and
      sham-operated rats treated with DOCA-salt. RESULTS: In AP intact (API) rats,
      after one week of DOCA-salt treatment BP began elevating to statistical
      significance at the end of the second week (MAP 15.9 +/- 0.7 vs. 13.5 +/- 0.5
      kPa), followed by a plateau period from the third to fifth week. In AP ablated
      (APX) rats, BP raised during the first week of DOCA-salt treatment. However, the
      elevation gradually disappeared and BP returned to baseline at the fifth week.
      Sodium balance study showed that DOCA-salt treatment induced significant sodium
      retention in API rat, while the sodium metabolism remained stable in APX group
      except in the first week. Basal renal hemodynamic parameters (GFR, RPF, UNaV, UV)
      were not changed at neither the beginning nor the end of the study. However, a
      small dose of hypertonic saline (7% NaCl 0.3 ml) injection caused a brisk rising
      of these four parameters in APX but not API group. CONCLUSION: AP plays an
      important role in normal salt and water metabolism and might be involved in
      pathogenesis of DOCA-salt hypertension through regulation for renal hemodynamics
      and body fluid homeostasis.

PMID- 9275485
TI  - [Expression of cytokines in labial gland of Sjogren's syndrome].
AB  - OBJECTIVE: To explore the role of cytokines in the process of inflammation and
      destruction of minor salivary gland in Sjogren's Syndrome. (SS) METHODS: Using in
      situ non-isotope double hybridization method, we detected the mRNA of the
      following cytokines: TNF alpha, IL-1 beta, IL-6, PDGF alpha and PDGF beta in 24
      labial gland biopsied sections. RESULTS: No cytokine could be detected in the
      normal labial glands sections. The positivity of all cytokine expression was
      higher in the pSS and sSS patients than that in the control. The intensity of TNF
      alpha expression was 3-4 fold increase in pSS compared with sSS. The different
      cytokines were expressed with the different grade of lymphocytic focus. The site
      of different cytokines was also expressed differently. The coexpression of mRNA
      of TNF alpha and IL-1 beta or TNF alpha and IL-6 was only seen in the
      inflammatory mononuclear cells but not others. The expression of TNF alpha in
      aciniar cells could occur earlier than the infiltration of lymphocytes in the
      interstitial region. It was found that the IL-6 positive group had higher
      positivity of serum ANA compared with the IL-6 negative group according to Ridit
      statistical analysis (P < 0.05). The serum anti-SSA and anti-SSB antibody had an
      increase tendency in the IL-6 positive group. CONCLUSION: We hypothesize that the
      development of SS may be secondary to some trigger agents, which activated the
      aciniar cells in exocrine gland of predisposed individuals. The activated acini
      cells secreted TNF alpha, then TNF alpha induced other cytokine expression,
      followed by the lymphocytes infiltration, which led to autoimmne reaction and the
      destruction of the exocrine gland.

PMID- 9275486
TI  - [Establishment of labeled primer reverse transcription in situ polymerase chain
      reaction and detection of hepatitis C virus in liver tissues].
AB  - OBJECTIVES: To establish bio-11-photosoralen (BP) labeled primer reverse
      transcription in situ polymerase chain reaction (RT-in situ PCR), and detect the
      location and distribution of hepatitis C virus in 17 cases liver tissue embedded
      by paraffin. METHODS: The method was compared with indirect RT-in situ PCR and in
      situ hybridization for detecting hepatitis C virus (HCV) RNA. RESULTS: The
      results of serum HCV PCR and southern blot showed that BP labeled primer PCR not
      only is possible, but also has a good specialty. The HCV positive rate was 59%
      (10/17) by indirect RT-in situ PCR, 53% (9/17) positive specimens were found by
      BP labeled primer RT-in situ PCR. Statistical analysis revealed that chi 2 volume
      was 0.12, P > 0.05, the two methods had no dominantl differences. Meanwhile only
      24% (4/17) positive signals were seen by in situ hybridization, which was lower
      than two RT-in situ PCR, chi 2 volume was 3.97 and 4.37 respectively, P < 0.05.
      Moreover, HCV was mainly located in hepato-plasmas, but positive signals were
      found in monocytes and cholangiolar epithelia. CONCLUSIONS: We conclude that both
      indirect RT-in situ PCR and BP labeled RT-in situ PCR have the good sensitivities
      and specialties for detecting HCV RNA of liver tissues, and HCV RNA locates not
      only in hepatocytes, but also in monocytes and cholangiolar epithelia. The
      results suggested that hepatocytes may be not only replicate location of
      hepatitis C virus.

PMID- 9275487
TI  - [Pedigree investigation of familial non-insulin dependent diabetes mellitus].
AB  - To discuss the inheritant mode of familial NIDDM. METHODS: According to WHO
      criteria of DM, 100 NIDDM Probands with family history of DM were diagnosed and
      100 persons were chosen at random for controls. The survey of DM was performed in
      both groups, including FBG, HbAlc, FINS. Some members had insulin release test.
      RESULTS: The prevalance rates of DM in familial DM group were 26 times of the
      control group (34.3% and 1.3%). The prevalance rate of DM among first-degree
      relation was 18 times higher than that in general population (28.3% and 1.5%).
      The rate of diabetes in the siblings and in the off-springs was 44.4% and 9.7%
      respectively. The pedigree analyses showed that 83.9% affected families had one
      diabetic parent, one half siblings had DM, and there was a successive
      transmission of DM through at least three generations in sixteen large families.
      Besides, the incidence of DM was much higher in females than in males (40% and
      28%). Among affected parents, diabetlic mothers were much more than diabetic
      fathers (50.8% and 27.6% P < 0.01). CONCLUSION: Familial NIDDM had a familial
      aggregation. It was inherited in the manner of Mendelian autosomal dominant
      inheritance. The difference between the rate in DM mothers and fathers was
      probably due to unequal prevalance rate in females and males.

PMID- 9275488
TI  - [Intellectual status of patents cerebral cysticercosis].
AB  - OBJECTIVE: To study the intellectual status of patients with cerebral
      cysticercosis with dementia evaluation scale. METHODS: The intellectual status of
      112 patients with cerebral cysticercosis was studied with Hasagawa dementia
      evaluation scale and that of 30 patients with event related potential of P 300.
      RESULTS: In the patientsl, 50.9% suffered from mental dysfunction. Among them
      11.6% had severe abnormality, 13.4% moderate, and 25.9% mild. Hypertension,
      epileptic attack and improper medication may cause intellectual dysfunction.
      CONCLUSIONS: Protection of mental function should be considered when chosing the
      treatment for better recovery of the patients. Hypertension, epileptic attack and
      improper medication may cause intellectual dysfunction.

PMID- 9275489
TI  - [Epidemiological survey of Graves' disease on a hundred thousand people in Daging
      area].
AB  - OBJECTIVE: To study the incidence of Graves' disease and associated factors.
      METHODS: A total of 100123 people aged 15-79 in Daqing region were surveyed
      epidemiologically. The investigations were conducted for an average two years.
      RESULTS: 301 patients with Graves' disease were newly diagnosed, 74 of them
      (1.6/1000) were males and 227 (4.1/1000) females. The total incidence was
      3.0/1000. The incidence had significant differences between ages and occupations.
      Investigations of 18 associated factors for Graves' disease by using the Logistic
      multivariate regression analysis showed the following pathological factors, virus
      history, psychological stimulation, food, drugs, family history, education,
      distributions, etc. CONCLUSION: This study may provide the theoretical evidence
      for prevention and treatment of Grave's disease.

PMID- 9275490
TI  - [The expression of pulmonary surfactant proteins B and surfactant protein C in E.
      coli].
AB  - OBJECTIVE: To express biological active surfactant protein B(SP-B) and surfactant
      protein C(SP-C) combined with synthetic phospholipids to make an ideal exogenous
      pulmonary surfactant (PS) for the treatment of respiratory distress syndrome
      (RDS) in future. METHOD: Prokaryote expression vector pIN-II-ompA2-B-C was
      established with the cDNA fragments of mature human SP-B and SP-C, then the
      fusion protein of mature SP-B with SP-C was expressed in E. coli BL21 induced by
      IPTG. The expression of fusion protein in E. coli was confirmed by Western blot
      anlaysis. The biological activity of the expressed product was measured by
      Wilhelmy's surface balance (MTP-2). RESULTS: The fusion protein of SP-B with SP-C
      could be expressed in E. coli BL21, and their molecular weight (Mr) was 20000 on
      gel electrophoresis, but the amount was small. According to the measurement of
      Wilhelmy's surface balance (MTP-2), the minimal surface tension of expressed
      protein in E. coli BL21 could be reduced to 0.004 N/m2 and the area of hysteresis
      loop was relatively large. CONCLUSIONS: The results of the investigation will be
      a basis to obtain SP-B and SP-C with gene engineering technology and to create a
      new way for producing ideal exogenous PS.

PMID- 9275491
TI  - [Screening for mutations in the PAH gene in Chinese: a new splice and a novel
      polymorphic mutation].
AB  - OBJECTIVE: to screening for novel mutations in the phenylalanine hydroxylase
      (PAH) genes in Chines as to investigate the molecular basis of phenylketonuria
      and to raise its diagnosis rate. METHODS: We applied the polymorase chain
      reaction (PCR) on amplified DNA fragment harboring exon 4 of the PAH gene. For
      novel mutations detected, the amplified fragments were sequenced by using ds-DNA
      cycle-sequencing method. RESULTS: Seven out of 24 cases of PKU had different
      kinds of band-shifting, which are subjected to two patterns of polymorphism. The
      first one, only in one case, has one mutation band migrating before the normal
      bands, while, the second one, which was common among the cases, had both the
      mutation bands running ahead of the normal bands. By sequence analysis, these
      polymorphic patterns corresponded to two noval mutations. One was a GT-->AT
      substitution at the 5' splice donor site of intron 4, and the other is an A to C
      transversion at position-11 of intron 3. CONCLUSION: The two mutations are both
      first reported. The 5' donor splicing mutation may result in skipping of the
      preceeding exon during RNA processing. The A to C transversion, which accounted
      for about 20% of the Chinese PKU alleles is a polymorphism changes.

PMID- 9275492
TI  - [Ultrastructural study of the extraocular muscles from congenital nystagmus].
AB  - OBJECTIVE: To study the pathogenesis of congenital nystagmus. METHODS: We
      observed the ultrastructure of extraocular muscles from congenital nystagmus
      patients with transmission electron microscope. RESULTS: As to extraocular muscle
      in congenital nystagmus of jerky type, there wre myofibrillae perpendicular to
      axes of myocytes within the myocytes in the quick phase side. This kind of
      myofibrillae had the structure of sarcomeres. In slow phase side, there were
      perpendicular myofibrillae in the periphery of myocytes and the adjacent nuclear
      region. There was dense nuclear matrix within myocytes and the membrane of
      nucleus was intact. With regard to pendular type of congenital nystagmus, there
      was no perpendicular myofibrillae within myocytes. The myofibrillae parallel to
      the axes of myocytes were arranged disorderly. The length of sarcomeres in
      different myofibrillar was not identical. Within myocytes of different types of
      congenital nystagmus, there was a large amount of mitochondria, in which the
      inner crest was arranged disorderly and there was vacuole formation. CONCLUSION:
      This study demonstrates that congenital nystagmus has the pathological basis of
      ultrastructural changes.

PMID- 9275493
TI  - [Quality control of biological therapy in patients with tumors].

PMID- 9275494
TI  - [Mechanisms of resistance to melphalan in leukemia cell line and reversal by
      interferon alpha].
AB  - OBJECTIVES: To study the mechanisms of resistance to alkylating agent melphalan
      (Mel) in leukemia cell and to investigate effect of modulation of resistance to
      Mel by IFN alpha. METHODS: A Mel-resistant variant of the leukemic cell line
      (K562/Mel) was developed in vitro by continuous exposure to Mel. The level of
      expression of several resistance-related gene in K562/Mel and the effect of
      reversal of resistance to Mel by IFN alpha were observed. RESULTS: K562/Mel was
      8.0-fold resistant to Mel and also cross-resistant to nitrogen mustand and
      thiophosphoramide, but not to carmustine and doxorubicin. This enhanced Mel
      resistance was associated with increased level of GST alpha gene and total GST,
      but not with increased level of expression of GST pi, GST mu, MDR-1 and Top-II
      gene. IFN alpha, at 500 IU/ml, a noncytotoxic dosage significantly increased the
      cytotoxicity of Mel to K562/Mel. The reversal of Mel resistance is related to the
      decrease of the level of expression of GST alpha gene. CONCLUSION: Resistance to
      Mel is associated with increased level of GST alpha gene and total GST in
      leukemic cell. IFN alpha can reverse Mel resistance.

PMID- 9275495
TI  - [The changes of striatal dopamine levels in the brain in rat models for
      Parkinson's disease after gene therapy].
AB  - OBJECTIVE: To examine the levels of striatal dopamine and metabolic products in
      rat model of Parkinson's disease (PD) by intracerebral grafting of the
      genetically modified muscle cells expressing tyrosine hydroxylase (TH). METHODS:
      The levels of striatal dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic
      acid in the striatum of rat models for PD were determined by using high
      performance liquid chromatography (HPLC). The tests were done in 2, 4, 12, 20 and
      23 weeks after intracerebral transplantation of cultared muscle cells (myotubes)
      expressing TH gene. RESULTS: The levels of dopamine and its metabolites in the
      striatum increased significantly after transplantation of TH-expressed cultured
      muscle cells. For example, striatal dopamine level increased from 30.53 pg/mg to
      876.25 pg/mg in brain tissue at 12 weeks after grafting. The striatal dopamine
      level was the highest at this time and then decreased gradually. In the control
      that received transplantation of muscle cells expressing LacZ gene, the striatal
      dopamine level showed no changes before and after grafting. CONCLUSIONS: The
      transplantation of TH gene-expressed cultured muscle cells is useful in the
      treatment of PD rat model, because it can increase striatal dopamine level.

PMID- 9275496
TI  - [The in vitro antitumor responses of murine peritoneal macrophages induced by
      adenovirus-mediated IL-4 and/or M-CSF gene therapy].
AB  - OBJECTIVE: To observe the antitumor responses of murine peritoneal macrophages
      induced by adenovirus-mediated IL-4 and/or M-CSF gene transfer. METHODS: The IL-4
      gene and/or M-CSF gene was transfected into murine peritoneal macrophages
      mediated by adenovirus and the levels of IL-4, M-CSF, TNF, IL-1 and NO in the
      supernatant of the macrophages and the cytotoxicity of the macrophages to tumor
      cells were assayed. RESULTS: The high levels of IL-4 and M-CSF could be detected
      in the supernatant of macrophages 18 hours after being infected with advenovirus
      expressing IL-4 or M-CSF. The cytotoxicity of the macrophages engineered to
      secrete IL-4 or M-CSF increased significantly, and when IL-4 gene and M-CSF gene
      were cotransfected into the macrophages or the macrophages were co-stimulated
      with LPS, the cytotoxicity increased even more significantly. The levels of TNF,
      IL-land NO in the supernatant of macrophages also increased. CONCLUSION: The
      results demonstrated that transfection of IL-4 and/or M-CSF gene into macrophages
      could augment their anti-tumor immunity.

PMID- 9275498
TI  - [Analysis of DNA methylation pattern of c-myc oncogene in hepatocellular
      carcinoma].
AB  - OBJECTIVES: To assess whether hypomethylation of c-myc gene occours in HCC and to
      determine its clinical significance. METHODS: The methylation pattern at 3' end
      of c-myc gene was analyzed by Southern blot using methylation sensitive
      restrcition endonuclease enzymes Hpa I and Msp I in six normal liver tissues and
      18 HCCs. RESULTS: At least 5 CCGG sites were methylated at 3' end of c-myc gene
      in 6 normal liver tissues. However, the normal hypermethylation pattern was
      absent in 11 hepatocellular carcinoms (HCC) which showed different degree of
      hypomethylation even if among subclonal cells of same tumour tissues. The
      hypomethylation was observed more often in markedly advanced HCC with metastasis
      and poorly differentiated histological grade. CONCLUSION: Scattered CpG at 3' end
      of c-myc gene was methylated in normal liver tissues. Methyl groups were deleted
      in different extent in HCC, which can lead to abnormal expression of c-myc gene.
      The hypomethylation of c-myc can reflect the malignlant extent of HCC and may
      serve as a useful prognostic indicator in clinical practice.

PMID- 9275497
TI  - [The protective effect of nicotinamide on interleukin-1 beta induced damage to
      rat islets of Langerhans and its mechanism].
AB  - OBJECTIVE: To investigate the protective effects of nicotinamide (NA) on newborn
      rat islets of Langerhans. METHODS: Newborn rat islets were isolated by digestion
      of collagenase V. The effects of IL-1 beta and/or NA on insulin release and
      nitric oxide (NO) production and 3H-thymidine incorporation were studied.
      RESULTS: NA had no effects on both accumulated insulin release and insulin
      release at an acute glucose challenge, but increased 3H-thymidine incorporation.
      25 mmol/L of NA reduced the inhibition of accumulated insulin release and 3H
      thymidine incorporation induced by 40/ml of IL-1 beta. However. NA was not able
      to reverse the reduced ability of IL-1 beta-treated islets to respond to an acute
      glucose challenge. NA dose-dependently reduced NO production induced by IL-1
      beta. CONCLUSION: There is the protective effect of NA on IL-1 beta-induced
      damage to islets of Langerhans. The mechanism of this effect might be related to
      that NA stimulates islet cells replication and reduces NO production induced by
      IL-1 beta.

PMID- 9275499
TI  - [IL-2, IL-2R mRNA gene expression and protein production].
AB  - OBJECTIVE: To analyse IL-2, IL-2R mRNA gene expression and protein production
      before, during, and after rejection of heart transplantation in vitro model.
      METHOD: The in vitro system consists of peripheral PBMC of health donor as
      response cells and cardiomyocytes of patient suffering from acyanotic congenital
      heart disease as stimulating cells. Reverse transcription-polymerase chain
      reaction (RT-PCR) was used. RESULTS: mRNA transcription and protein production of
      IL-2, IL-2R rose markedly after stimulation of alloantigen, and were different
      from those of the control (P < 0.05, P < 0.01). The summit of IL-2, IL-2R mRNA
      transcription was detected 24 hours after initiation of mixed culture, 48 hours
      earlier than the time (72 hours) at which damage of cardiomyocytes was detected
      electronmicroscopy and the peak of IL-2, IL-2R protein production detected.
      CONCLUSION: IL-2/IL-2R system plays an important role in the rejection of heart
      transplantation. Detection of IL-2, IL-2R mRNA transcription is significant for
      early diagnosis of rejection. RT-PCR makes analysis of mRNA rapid, and is
      sensitive and high specific.

PMID- 9275500
TI  - [The protective effects of dichloroacetate on cerebral ischemia after reperfusion
      of fed rats].
AB  - OBJECTIVE: To study the brain protective mechanisms of dichloroacetate (DCA) by
      observing the influence of DCA on the biochemical and pathological changes in
      ischemic brain tissues in different periods of reperfusion. METHODS: The FED-RAT
      cerebral ischemic model induced by 4-vessel occlusion was applied. 55 mature male
      Sprague-Dawley rats were divided into the control group, normal saline and DCA
      treated groups before ischemia, normal saline and DCA-treated groups after
      ischemia equally and randomly. RESULTS: DCA could significantly lower the brain
      lactic acid, water content, and the diameter of cortical neurons, and protect the
      pathological damage of the membranaceous structure, before or after ischemia at a
      dose of 25 mg/kg, compared with the normal saline treated groups. CONCLUSION:
      Lowering brain lactate, resisting brain edema and protecting the membranaceous
      structures are the main brain protective mechanisms of DCA in biochemistry and
      ultrastructure.

PMID- 9275501
TI  - [The influence of perindopril on intrarenal RAS in experimental diabetic rats].
AB  - OBJECTIVE: To examine the effect of perindopril on the intrarenal renin
      angiotensin system (RAS) in diabetic rats. METHODS: Diabetes of rats was induced
      by a single injection of STZ. The rats were treated with perindopril (1 mg.kg-1.d
      1) and the controls were given insulin only. Plasma and intrarenal renin activity
      (PRA, TRA) and angiotensin I (PAT I, TATII) were measured by radioimmunoassay in
      the diabetic rats at 1, 3, 6 months. Message RNA (mRNA) expression of renal
      angiotensinogen (TATO) and TATII receptor (TATII R) was assessed by slot blot
      hybridization. RESULTS: At 6 month, TATII levels in the control group were
      significantly decreased compared with those of normal controls (P < 0.05), and
      TATII levels in perindopril treated rats were decreased remarkedly compared with
      those of the control group (P < 0.01). TRA was not different among the three
      groups at 3 to 6 months (P > 0.05). In slot blot hybridization TATII R mRNA
      expression in the control group was markedly increased compared with that of
      perindopril treated and normal control groups (P < 0.05, P < 0.01). TATO mRNA
      expression was not different among the three groups (P > 0.05) during the
      experimental period. CONCLUSION: The abnormalities of intrarenal RAS existed in
      STZ induced diabetic rats, including the decrement of TATII content and the
      enhancement of TATII R mRNA expression. Perindopril could further decrease the
      level of intrarenal TATII, and inhibit its receptor mRNA expression.

PMID- 9275502
TI  - [Three-dimensional echocardiography in evaluation of left ventricular systolic
      function after mitral valve replacement for chronic mitral diseases with
      preservation of mitral apparatus].
AB  - OBJECTIVE: To assess the global left ventricular performance in 24 normal
      subjects, 24 patients suffered from mitral valve disease (MVD) with mitral valve
      replacement (MVR), and 20 patients with mitral valve replacement with
      preservation of mitral apparatus (MVRP). METHODS: 3DE was used in comparion with
      the findings of radiography (RNA), two-dimensional echocardiography (2DE), and m
      mode (MME). RESULTS: EF in 10 patients with MVD as compared with RNA, 3DE showed
      a higher connection coefficient than 2DE and MME. The EF estimated by MME and 2DE
      showed no difference between NS and MVD groups, there were significant
      differences when compared with those examined by 3DE. Two, three months after
      opertion, the VED and VES in group of MVRP were significantly lower than those in
      group of MVR (P < 0.01), the EF of MVRP group was remarkably higher than that of
      MVR group (P < 0.05). CONCLUSION: 3DE has the ability to estimate the EF of left
      ventricle more accurately than 2DE and MMe, especially in the patients suffered
      from chronic MVD with LV shape deformation. The MVR with preservation of mitral
      apparatus for chronic MVD is beneficial to maintaining the global systolic
      function after surgery.

PMID- 9275504
TI  - [The effect of splenectomy on alveolar macrophages morphology and function].
AB  - OBJECTIVE: To study the morphological and functional changes of pulmonary
      alveolar macrophages of rats after splenectomy, and the applied effects of
      splenic tissue autotransplantation in practice. METHODS: 87 Wistar rats were
      randomly divided into shamoperation group, splenectomy group and splenic tissue
      autotransplantation group. Six months after splenectomy, alveolar macrophges were
      subjected to brochoalveolar lavage described by Shennib. The dynamic survival and
      adherent rate of alveolar macrophages in culture, lysosomal enzyme content,
      hydrogen peroxide production and expression level of interleukin 1 (IL-1)
      activity of alveolar macrophages were quantitatively measured. The alveolar
      macrophages ultrastructure was observed by utilizing transmission electron
      microscope. RESULTS: The splenectomized rat's alveolar macrophages were different
      from alveolar macrophages of sham-operated rats. Their surface filopodia was
      reduced and shortened, lysosome fewer and its acid phosphatase quantity
      decreased, adherence postponed, hydrogen peroxide production and expression of IL
      1 activity impaired. Splenic tissue autotransplantation fairly restored the
      splenic effects on maturation and function of alveolar macrophages. CONCLUSION:
      Splenic tissue autotransplantation is a simple useful operation for preserving
      splenic function after splenectomy.

PMID- 9275505
TI  - [A comparative morphometric and histologic study of five bone substitute
      materials].
AB  - OBJECTIVE: To investigate and compare the osteogenesis of bone substitute
      materials. METHODS: 52 Chbb: ch rabbits were divided into 5 groups. Five
      different porous biomaterials, including natural bovine hydroxyapatite (Bio-OSS,
      BK V/1), semi-synthetic coral hydroxyapatite interpore 500, synthetic tricalcium
      phosphate CEROS 82 and glass POROLITH, were implanted together with free
      periosteum into the muscle of rabbits for up to 3 and 6 weeks. Undecalcified
      sections were prepared for microradiography, light and UV microscopy, and
      morphometry. RESULTS: Bone ingrowth was present in all such implantats. Bone
      formation was limited to the periphery of the Ceros blocks, that are lack of pore
      interconnection, while the other 4 materials with an interconnected porous system
      were infiltrated by bone into the centrum. Planimetric analyses showed that the
      specimens were composed of 6.5%-19.0% new bone at the 3rd week and 14.2%-25% at
      the 6th week respectively. The difference of bone ingrowth was only significant
      between Bio-OSS and BK V/1 at the 3rd week. No statistically significant
      difference of bone volume was found within the 6 week groups. There was a
      positive correlation between the new bone volume and the porosity of the
      materials. CONCLUSION: For the bone ingrowth, the structure of the materials,
      specifically the pore and pore interconnections, is more impatant than the
      chemical composition.

PMID- 9275503
TI  - [Obesity may have more pronounced effect on the occurrence of insulin resistance
      than hypertension].
AB  - OBJECTIVE: To compare the extent of insulin resistance in hypertensive and in
      obesity patients and verify their role on the occurrence of insulin resistance.
      METHODS: Insulin sensitivity was assessed by using euglycemic insulin clamp
      technique (EICT) in normal subjects (NS, n = 36), obesity (n = 23), hypertensive
      non-obesity patients (HT+nonobesity, n = 51) and hypertensive and obesity
      patients (HT+obesity, n = 54) Glucose metabolism ratio (M) served as an index of
      insulin sensitivity. RESULTS: The height sequence of M value was: NS >
      HT+nonobesity > obesity > HT+obesity (ie, 9.2 +/- 1.0 > 7.6 +/- 2.0 > 6.7 +/- 1.5
      > 5.2 +/- 1.8 mg.kg-1.min-1, P < 0.05). The incidence rate of decreased insulin
      sensitivity among the four groups was: HT+obesity > obesity > HT+nonobesity > NS
      (87.0%, 69.6%, 41.1% and 2.8%, P < 0.05). After adjusting for age, sex and BMI, M
      value was greater in normotensives (n = 59) than in hypertension patients (n =
      105) (8.0 versus 6.6 mg.kg-1min-1, P < 0.01). Multivariates analysis showed that
      BMI and SBP are the two most important determinants for M value, but the effect
      of 1 kg/m2 BMI is equivalent to that of 20 mmHg SBP. CONCLUSION: Decreased
      insulin sensitivity may be the common linkage between obesity and hypertension.
      Obesity may have more pronounced effect on insulin sensitivity than hypertension.

PMID- 9275506
TI  - [The relationship between peripheral edema and right heart function in COPD
      induced cor pulmonale].
AB  - OBJECTIVE: To estimate the role of right heart function in the development of
      edema in COPD induced cor pulmonale. METHOD: 44 cases in exacerbation stage with
      hypoxia and hypercapnia were studied. Pulmonary hemodynamic parameters were
      measured by Swan-Ganz catheter and compared with the presence and extent of
      peripheral edema. RESULTS: Peripheral edema was noted in 40 cases and right
      arterial pressure < or = 1.33 kPa in 23 cases (23/40 = 57.5%), 17 cases showed
      edema, with right artrial pressure > 1.33 kPa. There was no significant
      difference in peripheral edema between that two groups. CONCLUSION: A high
      proportion of COPD patients with edema do not show right heart failure. The
      development of edema in COPD may be related to a complex mechanism, including
      hypoxia and hypercapnia induced natrium and water retention, Right heart failure
      is not a prerequisite for edema. The significance of edema in COPD induced cor
      pulmonale should be interpreted correctly in clinical practice.

PMID- 9275507
TI  - [Isolation of specific DNA probes from Cryptococcus neoformans].
AB  - OBJECTIVE: To construct plasmid library and screen specific DNA probes for
      Cryptococcus neoformans. METHODS: Serotype A Cryptococcus neoformans was used as
      the study strain, plasmid pUC18 as vector, and Escherichia coli JM103 as host
      cell. The plasmid library of cryptococcus neoformans was constructed (pCN). Other
      pathogenes causing affection diseases which should be distinguished from
      cryptococcusis clinically, and other fungi similar to Cryptococcus neoformans
      with physiological and biochemical characteristics were used as a distinguishing
      system, specific colonies were screened by hibridization in double steps.
      RESULTS: The inserts of the library were 280 to 1800 base pairs and 580 base
      pairs in average length. Repeated sequence was 32.43% and single copy sequence
      was 67.57% in genome of cryptococcus neoformans respectively. Three specific
      colonies were isolated from the library. Colony pCNII A6 was serotype A specific,
      pCNII B5 species specific and pCNIII G1-specific for var. neoformans. CONCLUSION:
      A rapid diagnosis of Cryptococcus neoformans infection at early stage can be made
      by using species-specific probe, and serotype and variaty of neoformans and
      gattii be distinguished in epidemic study.

PMID- 9275508
TI  - [Advances in the study of anesthesia in patients with carcinoid syndrome].

PMID- 9275509
TI  - [Critically ill patients: anesthesia and perioperative management].

PMID- 9275510
TI  - [Summary of national symposium on anesthesia and perioperative management for
      critically ill patients].

PMID- 9275511
TI  - [Nitric oxide delivery through ventilator and its toxic oxidative product
      nitrogen dioxide].
AB  - OBJECTIVE: To observe nitric oxide(NO) delivery through mechanically ventilator.
      NO is rapidly converted to nitrogen dioxide(NO2)in oxygen(O2) environments.
      METHODS: NO(800 ppm)was blended with compressed air, delivered to the high
      pressure air inlet of a Siemens Servo 900C or VIP BIRD ventilator, and used to
      ventilator as a test lung. The ventilator settings were varied, minute
      ventilation (VE)from 2 to 6 L/min, inspired O2 fraction(FiO2)from 0.25 to 0.65,
      and NO concentration from 10 to 80 ppm. The inspiratory gas mixture was sampled
      just at the outlet port of ventilator. NO and NO2 were measured both by
      hemiluminescence and electro-chemical fuel cell technique. RESULTS: No NO was
      detected during any trial with VE 5 or 6 L/min., with FiO2 0.35 or 0.25, with NO
      20 or 10 ppm. Low VE and low NO, NO2 values were greater with Servo 900C
      ventilator than with VIP BIRD ventilator at similar settings High VE and low NO
      or low VE and high NO, NO2 values were similar with both ventilators. High VE and
      high NO, NO2 values were greater with VIP BIRD ventilator than with Servo 900C
      ventilator. At same VE, NO2 values increased with increased FiO2 and NO. (NO2) =
      0.0607 (NO)- 0.6604 VE + 7.004 FiO2, R2 = 0.7649 with Servo 900C ventilator,(NO2)
      = 0.0929(NO)- 0.1296 VE + 7.9360 FiO2, R2 = 0.8687 with VIP BIRD ventilator.
      CONCLUSIONS: NO(800 ppm) was blended with compressed air, delivered to the high
      pressure air inlet of a Siemens Servo 900C or VIP BIRD ventilator is a portable,
      accurate, and adaptable system to deliver NO. During NO inhalation, VIP BIRD
      ventilator is more adaptable while low VE. Servo 900C ventilator is more
      adaptable while high VE.

PMID- 9275512
TI  - [The effects of cardioplegia and reperfusional blood containing captopril on
      myocardial ultrastructure alterations after cardiac arrest].
AB  - OBJECTIVE: To investigate the myocardial protective effect of captopril on the
      ischemia and reperfusion injury in the canine heart. METHODS: Twelve mongrel dogs
      were randomly divided into control and captopril groups. In the former, only
      modified St. Thomas cardioplegia was used, and in the latter, modified St. Thomas
      cardioplegia and reperfusional blood containing 4.6mumol/L captopril were used.
      Sixty minutes after reperfusion, myocardial renin activity (MRA), angiotensin II
      (AII) and melondyldialdehyde (MDA) content in myocardium were measured, and the
      subendocardial myocardium of the left ventricle was taken for electromicroscopy.
      RESULTS: The MRA in the Cp1 group was significantly higher than that in the
      control group (P < 0.01), while the AII and MDA content in the myocardium in the
      Cp1 group were significantly lower than those in the control group (P < 0.01).
      Electronmicroscopically, the damage of the myocardium including sarcomeres,
      mitochondria and microvascular endothelial cells were less obvious in the Cp1
      group than that in the control. The mitochondrial average cross-section area and
      average volume (0.59 +/- 0.15 micron2 and 0.74 +/- 0.23 micron3) in the Cp1 group
      were significantly lower than those in the control (0.83 +/- 0.34 micron2, P <
      0.01 and 1.1 +/- 0.4 micron3, P < 0.01). The numerical density (0.46 +/- 0.16
      micron-3), specific surface of mitochondria (6.4 +/- 1.1 microns-1) and
      memberance density of mitochondrial cristae (21 +/- 10 microns-1) in the Cp1
      group were significantly higher than those in the control (0.29 +/- 0.06 micron
      3, P < 0.05, 4.8 +/- 0.8 micron-1, P < 0.01 and 15.3 +/- 2.0 microns-1, P <
      0.01): CONCLUSION: Cardioplegia and reperfusional blood containing 4.6 mumol/L
      captopril could effectively protect the myocardial mitochondria and microvascular
      endothelial cells against ischemia and reperfusion injury.

PMID- 9275513
TI  - [Role of nitric oxide in hemodynamic and extravascular lung water in a dog
      endotoxin shock model].
AB  - OBJECTIVE: To verify the effects of nitric oxide pathway modification on
      hemodynamics and extravascular lung water during sepsis. METHODS: Experiments
      were conducted in three groups of anesthetized dogs with sodium pentobarbital. In
      group 1 (n = 8), lipopolysaccharide was injected intravenously to produce
      endotoxin shock. Group 2 (n = 8) received both lipopolysaccharide and L-arginine,
      a precursor of nitric oxide synthesis, intravenously. Group 3 (n = 8) received
      both lipopolysaccharide and N-nitro-L-arginine (L-NNA), a competitive inhibitor
      of nitric oxide generation, intravenously. Hemodynamic data included MAP, CVP,
      PAP, PAWP, CI, SI, SVRI, PVRI, LVSWI and RVSWI were measured or calculated.
      Oxygenational data included DO2, O2ER, and VO2 were calculated. Extravascular
      lung water (EVLW) was measured. RESULTS: L-arginine increased CI (2.2 +/- 0.7 to
      2.7 +/- 0.7 L.min-1)/m2 and SI (15 +/- 3 to 19 +/- 5 ml/m2, P < 0.05) and
      decreased PVRI (320 +/- 86 to 211 +/- 87 dyne. sec/cm5-m2, P < 0.05) without
      significant changes in O2ER, DO2 and VO2. All of the untoward hemodynamic effects
      of endotoxin were exacerbated by the addition of L-NNA (CI-56 +/- 2%, SI -58 +/-
      5%, P < 0.05, SVRI + 170 +/- 10%, PVRI + 129 +/-15%, P < 0.01). As DO2, was
      significantly decreased by L-NNA (534 +/- 104 to 300 +/- 90 ml.min-1/m2, P <
      0.01), therefore, O2ER was also increased (insufficiently), and VO2 was still
      decreased significantly (146 +/- 58) to 115 +/- 38 ml.min-1/m2, P < 0.05. EVLW
      was markedly increased by L-NNA (5.4 +/- 1.0 to 6.2 +/- 0.7 g/kg, P < 0.01).
      CONCLUSIONS: The inhibition of nitric oxide synthesis has serious adverse
      hemodynamic and oxygenational consequences in our endotoxin shock model. We
      speculate that nitric oxide inhibition has no foreseeable therapeutic role in
      early stage of septic shock.

PMID- 9275514
TI  - [Immunoglobulin super-gene family and its related genes in detecting MRD in ALL].
AB  - OBJECTIVE: To study the rearrangements of the immunoglobulin super-gene family
      and its related genes, as well as their application in the detection of minimal
      residual disease (MRD) in acute lymphoblastic leukemia (ALL). METHODS: 15 ALL
      cases including 11 B-ALLs and 3 T-ALLs were studied separately by using
      immunophenotype detection and molecular clonging methods. RESULTS: Using DNA
      Southern blot analysis, we found that the rearrangement of IgH gene existed in 11
      B-lineage ALL cases. The specific PCR band was visualized through amplification
      of the CDR3 region and J region of IgH gene. Furthermore, we sequenced the V-D-J
      junctional region of IgH gene in 3 B-lineage patients and synthesized two probes
      against the V-D-J junctional region in order to detect MRD. The hybridization
      results showing the sensitive of the two probes were 10(-4). In addition, we
      performed comparative study of MRD detection by using both T cell receptor (TCR)
      gamma gene as gene specific marker and SIL-TAL-1 fusion gene as tumor-specific
      marker in one T-ALL patient. CONCLUSION: The rearrangements of IgH gene, as well
      as TCR gene and tumor fusion gene can be used as specific markers in the
      detection of MRD in ALL.

PMID- 9275515
TI  - [Yeast artificial chromosome cloning and physical mapping of retinitis pigmentosa
      3 (RP3) locus].
AB  - OBJECTIVE: To clone retinitis pigmentosa region by yeast artificial chromosome
      (YAC) and establish the restriction enzyme physical map. METHODS: The ornithine
      transcarbamoylase (OTC) cDNA probe, which is closely linked to the RP3 locus, was
      chosen to screen the X chromosome YAC library by colony in situ hybridization.
      Size determination, sequence taged site (STS) analysis and long range physical
      mapping were performed with positive YACs. The results obtained were used to map
      these YACs. RESULTS: We obtained a 1.6 Mb YAC contig containing information on
      RP3 range, restriction enzyme sites, CpG islands location and YAC position.
      CONCLUSION: The work provides a good basis for identification and cloning of the
      RP3 gene.

PMID- 9275516
TI  - [Recurrence of early gastric cancer].
AB  - OBJECTIVE: To evaluate the features of recurrence of early gastric cancer.
      METHODS: 109 cases of early gastric cancer were subjected to surgical resection
      from 1972 to 1988. Apart from two died, all cases were followed up for more than
      5 years. RESULTS: Eight cases (7.5%) died of other diseases. Ten cases (10.3%)
      died because of the recurrence of gastric cancer. Five cases (45.5%) had
      hematogenic metastasis to the liver or lung. Two cases had the recurrence of the
      cancer in lymph node. The recurrence in the residual stomach was found in 3
      cases, in addition to a patient who was detected to have metastasis in Virchow's
      lymph node survival for 12 years after operation. The recurrence rate was higher
      in submucosal tumors (12.8%) than in mucosal tumors (8.0%), in lymphatic and
      vascular vessel invasion-positive cases (43%) than in negative cases (7.8%), in
      synchronous multiple gastric cancer (33.3%) than in solitary tumors (7.2%), in
      tumors of 1.5 cm or more in diameter (11.5%) than in tumors of less than 1.5 cm.
      The rate of hematogenic metastasis to the liver or lung was 45.5% (5/11), and the
      recurrence in the residual stomach was 27.3% (3/11) and in lymph node was 27.3%
      (3/11). CONCLUSION: Hematogenic metastasis is frequent.

PMID- 9275517
TI  - [Expression of thyrotropin receptor gene in autoimmune thyroid disease and the
      relation to expression of HLA genes].
AB  - OBJECTIVE: To investigate the expression of TSH receptor in autoimmune thyroid
      disease (AITD) and the relation to expression of HLA I and II genes. METHODS: The
      TSH receptor transcript levels were examined in 10 human thyroid fragments by
      Northern blot analysis. Graves' disease 7, Hashimoto's disease 2, and 1 healthy
      thyroid gland. RESULTS: TSH receptor transcript levels were higher in Graves'
      disease than in Hashimoto's disease and healthy control. CONCLUSION: TSH receptor
      expression was inversely related to HLA I and II expression and lymphocyte
      infiltration.

PMID- 9275519
TI  - [Intestinal flora in renal allograft recipients].
AB  - OBJECTIVE: To explore the change of 10 kinds of intestinal flora in renal
      allograft recipients and its significance. METHODS: Ten kinds of intestinal flora
      in faeces were investigated in 30 renal allograft recipients by Kang Bai's
      classification of flora, and compared with 100 patients with diarrhea and 30
      normal controls. RESULTS: The number of enteric bacilli in renal allograft
      recipients (8.5 +/- 1.0 CFU/g) was increased more markely than in the diarrhea
      patients (7.7 +/- 1.1 CFU/g, P < 0.01). The number of bacteroid (7.8 +/- 0.6
      CFU/g), bifidobactercium (7.7 +/- 0.3 CFU/g), eubaclerium (7.2 +/- 0.6 CFU/g),
      and clostridium (7.8 +/- 0.5 CFU/g) in renal allograft recipients were decreased
      more markedly in than normal control (8.2 +/- 0.7 CFU/g, P < 0.01, 8.3 +/- 0.7
      CFU/g, P < 0.01, 8.1 +/- 0.9 CFU/g, P < 0.01, 8.0 +/- 0.8 CFU/g, P < 0.01), but
      the number of Bifidobactercum was higher than that is the diarrhea patients (7.3
      +/- 0.6 CFU/g, P < 0.01). The number of eubacterium was Lower than that in the
      diarrhea patients (7.7 +/- 0.8 CFU/g, P < 0.01). Among 30 renal allograft
      recipients 3 had constipation and 20 diarrhea. Two cases died of toxic shock with
      serious diarrhea because of imbalance of intestinal flora. CONCLUSION: The
      imbalance of intestinal flora existes in the early stage of renal
      transplantation. It is characterized by anaerobic bacilli imabalance such as
      bifidobacteriam and may be a direct cause of intestinal infection as diarrhea.

PMID- 9275518
TI  - [Therapeutic effect of trace element on ulcerative colitis experimental study].
AB  - OBJECTIVE: To produce a chronic UC model in rats, and study the therapeutic
      effects of trace elements on this UC model as well as the in possible mechanisms.
      METHODS: Male Wistar rats (100-150 g) were given drinking water containing 1.5%
      dextran sulfate sodium (DSS) to induced UC. Rats developed UC were divided into 4
      groups randomly, selenium group (Se group, Natural Selenium Liquid 6 ml.d-1,
      containing selenium 60 micrograms); zinc plus selenium group (ZS group, every rat
      was given zinc sulfate 180 mg.kg-1.d-1 and selenium 60 micrograms.d-1), while
      dexamethasone (7 mg.kg-1.d-1) was used as positive control and 0.9% NS as placebo
      control. All rats received enema twice a day for 15 days. Endoscopic and
      histologic scoring were carried out for assessment of the therapeutic effect of
      trace elements. Mucosal SOD activity, MDA content, zinc and selenium content and
      peripheral blood NK activity were assessed. RESULTS: The efficacy of ZS group was
      better than that of placebo control (P < 0.01), and there was no difference
      between ZS group and positive control (P > 0.05). An increased SOD activity and
      decreased MDA content were found after the combined administration of zinc and
      selenium. Zinc and selenium concentration of colonial mucosal were increased
      significantly, so did the NK activity of peripheral blood. CONCLUSION: The
      combined therapy of zinc and selenium is effective for UC treatment, of which the
      possible mechanism may be involved, A) concentrating in local mucus; B) acting as
      scavengers of oxygen-free radicals, protecting cell membrane from peroxidation;
      C) improving the function of immunosurveillance system.

PMID- 9275520
TI  - [Otoacoustic emission and auditory efferent function testing in normal subjects
      and patients with sensori-neural hearing loss].
AB  - OBJECTIVE: To examine the role of otoacoustic emission and function test of the
      auditory efferent system in evaluating of auditory functional status in both
      normal and diseased conditions. METHODS: Spontaneous and transient evoked
      otoacoustic emission and efferent function in terms of contralateral white noise
      induced transient evoked otoacoustic emission suppressions were tested and cross
      compared in 32 normal ears, 24 ears with cochlear hearing loss and 16 ears with
      retrocochlear hearing loss. RESULTS: Transient evoked otoacoustic emission
      amplitude and contralateral suppression, spontaneous otoacoustic emission
      incidence, peaks and frequency range were significantly reduced in cochlear
      hearing loss, while in retrocochlear hearing loss transient evoked otoacoustic
      emission and spontaneous otoacoustic emission levels were significantly higher
      than in cochlear hearing loss group and showed no suppression. CONCLUSION:
      Contralateral acoustic stimulation induced transient evoked otoacoustic emission
      suppression as an index of efferent function is clinically feasible. Combined
      otoacoustic emission and efferent tests are of great significance in evaluating
      cochlea status and auditory central mechanisms. Auditory efferent function is
      weakened in cochlear lesions and severely damaged in retrocochlear lesions.

PMID- 9275521
TI  - [An antisense oligodeoxynucleotides for NR1 suppressed seizures and reduced
      discharges in the temporal cortex slice in genetically epilepsy-prone rat].
AB  - OBJECTIVE: To investigate the effects of N-methyl-D-aspartate receptors (NMDAR or
      NR) and NR1 subunit on mechanism of initiation and development epilepsy of
      genetically epilepsy-prone rat. METHODS: Antisense oligodeoxynucleotices (ODN)
      techniques, intracerebroventricular injection and experiments in vitro in rat
      temporal cortex slices were used. RESULTS: An antisense ODN for NR1, or the
      correspond sense ODN and normal saline was administered intracerebroventricular
      (i.c.v., 100 micrograms in 10 microliters) once daily, respectively for three
      days. P77PMC rats with antisense ODN did not display clonic and tonic convulsion,
      or showed that significantly lowered seizure scores compared to control groups.
      Moreover, the frequency and amplitude of early seizure-like events (SLEs) and
      late reccurrent discharges (LRDs), which induced by lowing Mg2+, were reduced in
      entorhinal cortex of the temporal cortex slice. CONCLUSION: Our results suggested
      that NMDA receptors, specifically the NR1 subunit, may participate in the
      initiation and development of epilepsy of P77PMC rat.

PMID- 9275522
TI  - [Regional brain calcium change in rabbit cerebral ischemia].
AB  - OBJECTIVE: To study whether regional brain calcium change would be an important
      factor for ischemic neuranal damage and whether calcium antagonist would exert
      protective effects on cerebral ischemia. METHODS: OCPC autoanalyzer method, was
      used to measure the regional brain calcium and observe the influence of
      flunarizine (FNZ) 48 hours after the rabbit middle cerebral artery occlusion
      (MCAO). RESULTS: 48 hours after MCAO, the calcium in the ischemic middle cerebral
      artery territory was 10.8 times as much as that in the pseudo-occluded controls,
      and FNZ could significantly decrease the ischemic brain calcium (P < 0.05) and
      the ischemic cerebral edema (P < 0.01). CONCLUSION: Caoverload was animportant
      factor leading to ischemic neuronal death, and FNZ has protective effects on
      cerebral ischemia.

PMID- 9275523
TI  - [Azathioprine and its combination with methylprednisolone: preventive effect on
      chronic cerebral vasospasm].
AB  - OBJECTIVE: To study the effects of azathioprine alone and combined azathioprine
      and methylprednisolone on chronic cerebral vasospasm. METHODS: An animal model of
      "double subarachnoid hemorrhage" was established by two cisterna magna injections
      of non-heparinized autologous arterial blood (0.3 ml/kg). The preventive effect
      of azathioprine alone and its combination with methylprednisolone on chronic
      cerebral vasospasm was studied. By angiography of vertebrobasilar artery with a
      transfemoral catheter, assay of LPO (lipid peroxidation) was performed on BA
      wall. Chronic cerebral vasospasm following subarachnoid hemorrhage was noted and
      the drugs' effect on chronic cerebral vasospasm also observed. RESULTS: Seven
      days after subarachniod hemorrhage, the basilar arterial (BA) diameter was 87% +/
      26% of the original BA diameter, and LPO content of BA wall was 0.03 +/- 0.01
      nmol/mg in azathioprine group and 93% +/- 20% (BA diameter) and 0.02 +/- 0.01
      nmol/L (LPO content) in azathioprine plus methylprednisolone group. When the BA
      diameter was 53% +/- 19%, the LPO content was 0.11 +/- 0.05 nmol/mg in the
      control group. Pathological examination showed that azathioprine alone and its
      combination with methylprednisolone obviously reduced the damage to the BA wall.
      CONCLUSION: Azathioprine has preventive effect on chronic cerebral vasospasm,
      supresses the production of free radicals and reduces damage to the BA wall
      following subarachnoid hemorrhage. Combined azathioprine methylprednisolone has
      produces better effects when only lower dosage is used.

PMID- 9275524
TI  - [Advances in the study of mechanism of iron uptake and some related etiology].

PMID- 9275525
TI  - [Development and prospect of critical care medicine in China].

PMID- 9275526
TI  - [To promote socialization and high efficiency high quality of prehospital
      emergency care].

PMID- 9275527
TI  - [Prospect of the clinical uses of molecular biology in lung cancer].

PMID- 9275528
TI  - [Measures combating pre-hospital sudden death].
AB  - OBJECTIVE: To study pre-hospital sudden death so as to reduce the death rate.
      METHOD: 814 pre-hospital deaths were randomly selected from January 1990 to May
      1994 for a retrospective study. RESULTS: 616 deaths (75.7%) showed a history of
      cardiac disease and hypertension. The age for high sudden death rate ranged from
      50 to 69 years (53.9%). Most of the cases (87.8%) were found in their homes. 21
      cases (2.58%) successfully recovered. CONCLUSIONS: The key points to improve the
      success rate of pre-hospital sudden death are: completing Beijing Emergency
      Medical Center's emergency care network so as to decrease the emergency care
      radium and shorten the emergency care time; disseminating emergency care
      knowledge on CPR and CPR technique.

PMID- 9275529
TI  - [Effects of selective nitric oxide synthase inhibitor in sheep with endotoxic
      shock].
AB  - OBJECTIVE: To investigate the effects of S-methylisothiourea sulfate (SMT), a
      selective inducible nitric oxide synthase (iNOS) inhibitor, on hyperdynamic
      endotoxic shock sheep. METHODS: Endotoxic shock was induced by Escherichia coli
      endotoxin in both control (n = 8) and SMT groups (n = 8). SMT was given
      intravenously. Hemodynamic data, oxygen delivery derived parameters and
      intramucosal pH (pHi) were measured. RESULTS: The control group had a
      hyperdynamic state, similar to that of human septic shock. In the SMT group,
      blood pressure was maintained at baseline, and cardiac index (CI) was lower than
      that in the control group (P < 0.05). Oxygen extraction ratio (O2 ext) was
      increased up to 40% +/- 5% and was much higher than that of the control group (P
      < 0.01). Pulmonary artery pressure (PAP) was higher than that of the control
      group (P < 0.01), and pHi decreased gradually similarly to the control group.
      CONCLUSION: SMT restored the blood pressure and increased O2 extespecially in the
      gut, but decreased CI and oxygen delivery and increased PAP. So over inhibition
      of iNOS should be cautiously considered.

PMID- 9275530
TI  - [Experimental studies of high frequency jet ventilation improved by enhancing
      expiratory turbulence].
AB  - OBJECTIVE: To improve the effect on CO2 elimination during high frequency jet
      ventilation by enhancing expiratory turbulence. METHODS: Nine healthy dogs with
      steam-induced type I respiratory failure were basically applied with high
      frequency jet ventilation (HFJV), and high frequency two-way jet ventilation
      (HFTJV), HFJV combined with thoracicoabdominal compression (HFJV+TAC), and HFJV
      combined with thoracicoabdominal compression-decompression (HFJV+ TACD) randomly
      for 30 min, respectively. The parameters were determined and the Reynolds numbers
      (NR) were calculated. RESULTS: Reynolds numbers were more than 3000 in all
      patterns, suggesting that the airflow was turbulent. Expiratory Na was higher.
      The NR of the latter three patterns was more significantly higher than that of
      HFJV (P < 0.01). CO2 elimination was 126, 111, 137 ml. min-1 in the latter three
      patterns, respectively and significant (P < 0.05) or very significant (P < 0.01)
      compared with 98.0 ml.min-1 in HFJV. Corresponding changes occurred in PaCO2. NO
      significant differences (P > 0.05) were observed in hemodynamic parameters.
      CONCLUSION: HFJV combined with inverse jet or thoracicoabdominal compression or
      decompression on expiratory phase could enhance expiratory turbulence and
      facilitate CO2 elimination in 9 dogs with steam-induced type I respiratory
      failure.

PMID- 9275531
TI  - [Gene expression of HGF and its receptor in experimental hepatomas].
AB  - OBJECTIVE: To understand the regularity of changes of gene expression about HGF
      and its receptor (HGFR) in experimental hepatomas model of Wistar rats and the
      relationship between this change and tumor biological behaviour. METHODS: The
      gene expression of HGF and HGFR in the canceration course of rats was determined
      by using experimental hepatomas model of Wistar rats established by
      diethylnitrosamine (DENA), with digoxigenin-labled probe. RESULTS: The positive
      expression of HGF and HGFR was found in rats liver tissues, but it was different
      in distinct stages. The positive expression of HGF was the highest in
      precirrhosis stage, and next in the cirrhosis stage. The canceration stage was
      the same as in the normal group. The positive expression of HGFR was gradually
      increased following the canceration course and the canceration stage was the
      highest, but we didn't find the expression of HGFR in normal liver tissues.
      CONCLUSIONS: There are close relations between the gene expression of HGF and
      HGFR and evolution course during the canceration of rats liver. HGF and HGFR
      systems play an important role in regulating tumor growth and metastasis.

PMID- 9275532
TI  - [Gene expression of bFGF and intimal hyperplasia of autologous vein grafts in
      rats].
AB  - OBJECTIVE: To establish a model of autologous vein graft through translating
      jugular vein to aortic artery in 80 Wistar rats, and detect gene expression of
      basic fibroblast growth factor (bFGF). METHOD: In situ hybridization and reverse
      transcription polymerase chain reaction (RT-PCR) were used. RESULTS: The
      expression of bFGF mRNA was more decreased than that of normal artery and vein
      after transplantation, up to 1 week, the level of bFGF gene expression decreased
      to the lowest (P < 0.05). Two weeks after transplantation, bFGF transcripts
      recovered. CONCLUSION: bFGF released from dead and damaged cells of autologous
      vein graft not only is an important factor that promotes SMC proliferation, but
      also is a potent stimulator of endothelial regrowth.

PMID- 9275533
TI  - [Expression of protooncogene bcl-2 in thyroid tumors].
AB  - OBJECTIVE: To determine the expression of protooncogene bcl-2 in thyroid tumors
      and its relationship to the development and prognosis of the tumor. METHODS: 124
      cases of thyroid tissues (41 thyroid carcinomas, 53 thyroid adenomas, 20 thyroid
      tissues adjacent to cancer and 10 normal thyroid tissues) were
      immunohistochemically stained for bcl-2, by using bcl-2 protein monoclonal
      antibody. The positive-staining rates in different thyroid tissues were compared
      statistically. RESULTS: Bcl-2 immunoreactivity was found in thyroid carcinomas
      (43.9%), thyroid adenomas (22.6%), and thyroid tissues adjacent to cancer
      (15.0%). The positive-staining rate in thyroid carcinomas was higher than that in
      thyroid adenomas (P = 0.0439) and that in thyroid tissues adjacent to cancer (P =
      0.0430). In thyroid carcinoma, the higher positive-staining rates were found in
      the cases of undifferentiated carcinoma and follicular carcinoma, as well as in
      the cases of positive lymph nodes or at tumor stage II and IV. CONCLUSION: The
      results suggest that the over-expression of bcl-2, a possible prognostic marker
      of thyroid cancer, may be related to the development of thyroid tumor.

PMID- 9275534
TI  - [Morphological changes in intracranial and extracranial arteries of autopsy cases
      of cerebrovascular diseases].
AB  - OBJECTIVE: To determine the distribution and severity of arterial lesions of
      intracranial and extracranial arteries in stroke patients in Chinese. METHODS: We
      studied 120 consecutive autopsy cases including 100 cases of stroke (50-80 years)
      and 20 cases of cancer as controls (50-80 years). Medium intracranial arteries
      and their primary branches, small intracerebral arteries, arterioles and
      extracranial carotid arteries (from 16 cases only) were examined with light
      microscopy. RESULTS: The stroke patients had significantly lower mean LA-VA
      ratios of the medium sized intracranial arteries and their primary branches,
      small intracerebral arteries and arterioles than the controls (P < 0.001). The
      stroke patients had higher mean VW-VR ratios of these arteries than the controls
      (P < 0.001). Atherosclerotic narrowing of the medium sized intracranial arteries
      and their primary branch were more severe than those of the extracranial caotid
      arteries. Moreover, the proximal portion of the primary branch arteries was much
      more severe than that of extracranial caotid arteries (P < 0.01, P < 0.05) in the
      stroke patients. CONCLUSION: Stroke patients had atherosclerotic lesions of the
      intracranial medium sized arteries and their primary branches and sclerotic
      lesions of the small intracerebral arteries and arterioles. These pathological
      changes resulted in thickening arterial walls and narrowing arterial lumens.

PMID- 9275535
TI  - [Experimental study of immunity in anti-plasmodium infection on preserved spleen
      and splenectomized mice].
AB  - OBJECTIVE: To investigate the function of the spleen as well as the changes of
      splenic function after hemisplenectomy and hemisplenic autotransplanted in
      plasmodium yoelili infected mice (first and second infection). METHODS: 336 mice
      were divided into six groups: 1. total splenectomy, 2. hemisplenectomy, 3.
      hemisplenic autotransplanted, 4. sham-operation, 5. total splenectomy of 2nd
      infection, 6. sham-operation of the 2nd infection. 3 months after operation (1-4)
      or 15 day after 1st infection and operation (5-6) in mice intraperitoneal
      inoculations were initiated. RESULTS: 1. First infection: in total splenectomy
      group the antiplasmodium antibody reduced, the remanent rate of 51Cr-RBC in
      circulation was high, RBC count continously decreased, parasitized erytrocytes
      still were seen after 1 month. These changes were mild in the preserved spleen.
      But the production of antiplasmodium antibody and spleen uptake rate of 51Cr-RBC
      of the hemisplenic autotrans aplaned were rather lower than those of the
      shamoperate group. 2. Second lethal yoelli infection: in the mice of
      shamoperation of 2nd yoelii infection the parasitized erytrocyte was lower than
      that of shamoperated group, but the higher level antiplasmodium antibody and
      uptake rates of 51Cr-RBC of unit weight splenic tissue. CONCLUSIONS: Under the
      plasmodium infection preserved hemispleen alternate normal spleen to play the
      immunologic role, splenic tissue autotransplantation can fairly restore the
      partial function of spleen. Different preserved spleen method is a useful
      operation for clinic.

PMID- 9275536
TI  - [Smooth intramural and kink-resistant polyester vascular prosthesis].
AB  - OBJECTIVE: To study the healing effect, neointimal formation and patency rate of
      smooth intramural and kink-resistant polyester vascular prosthesis. METHODS:
      Experimental implantations of the smooth intramural and kink-resistant polyester
      vascular prosthesis of internal diameters of 0.6-1. Ocm were performed in
      segments of abdominal aorta and thoracic descending aorta. RESULTS: The patency
      rate was 100% in both abdominal aortic implantations and thoracic descending
      aortic implantations after postoperative observation for 425 days, while the
      total patency rate was only 70% in the crimped controls. The thickness of the
      neointimal linings of both implantation groups was determined, smooth intramural,
      kink-resistant polyester vascular prostheses were significantly thinner than that
      using crimped polyester vascular grafts (P < 0.001). CONCLUSION: Our study proves
      the feasibility of using smooth intramural and kink-resistant polyester vascular
      prosthesis to substitute small arteries with an internal diameter of 0.6-1. Ocm.

PMID- 9275537
TI  - [The internalization of immunotargeting drugs for hepatocellar carcinoma and its
      significance].
AB  - OBJECTIVE: To study the internalization law of immunotargeting drug for
      hepatocellular carcinoma and its significance. METHODS: Colloidal gold technique
      and the process of internalization of the immunotargeting drugs, Hab18-ADM and
      Hab25-ADM, against hepatoma in the targeting cells of human hepatoma cell line
      SMMC-7721 was used under an electron microscope. RESULTS: 80% of the target cells
      with gold-labeled particles on the cellular surfaces. The main way of
      internalization was invariably through a non-coated microinvagination. 18 hours
      after the intercellular internalization of immunotargeting drugs, the cytoplasmic
      vacuolization could be visible, even cellular necrosis. The control cells grew
      well. The above results indicate that after entering into the targeting cells the
      immunotargeting drugs degrade within the lysosomes, then, ADM arrives at its
      function site and plays the role of cell toxicity intranuclearly. CONCLUSION: The
      internalization of Hab 18-ADM and Hab25-ADM is effective, and possesses a good
      prospect in clinical application.

PMID- 9275539
TI  - [The sequences of intron 50 and 51 of DMD gene and the deletion mechanism of 51st
      exon].
AB  - OBJECTIVE: To investigate the relationship between the structural characters of
      50th and 51st introns and deletion mechanisms of 51st exon of DMD gene. METHODS:
      We cloned the 3.1 Kb-Hind I human genome DNA fragment containing the 50 and 51
      introns of DMD gene, sequenced the fragment completely, and analysed the
      character of the sequences with computer. RESULTS: The length of the fragment was
      3179, including the entire 51st exon and partial 50th and 51st intron sequences.
      There were 36 short tandom repeats, 22 direct and inverted repeats, and 8
      homologous sequences in the 50th and 51st introns. A TATA box was found in the
      intron 50 and it may be another new promotor of DMD gene. CONCLUSION: The
      hypothesis, which the recombination of repeat sequences may result in the
      deletion of 51st exon, is put forward.

PMID- 9275538
TI  - [In situ observation of the relationship between apoptosis and proliferation in
      large bowel carcinoma and its precancerous lesion].
AB  - OBJECTIVE: To investigate action of apoptosis in tumorigenesis by observation of
      the relationship between apoptosis and proliferation. METHOD: Using terminal
      deoxynucleotidyl transferase-mediated dUTP niok end labelling (TUNEL) technique,
      PCNA immunohistochemical staining, and HE staining, we observed the density and
      distribution of apoptotic cells, proliferating cells and mitotic cells in situ in
      15 normal mucosa, 32 villous adenoma and 33 papilloid adenocarcinoma of large
      bowel. RESULTS: The zone of apoptotic cells located in superficies and zone of
      proliferating cells in base in normal mucosa. These characteristics of
      distribution were lost in villous adenomas and papilloid adenocarcinomas of large
      bowel. The density of apoptotic cells in villous adenomas was significantly
      higher than that in normal mucosa and carcinomas. The density of apoptotic cells
      lowered and the density of proliferating cells rose in villous adenomas.
      Comparison of villous adenoma with papilloid adenocarcinoma, showed that
      apoptotic cells decreased and proliferating cells increased significantly.
      CONCLUSIONS: Through selectivity, the cells have highly proliferative ability
      prodominanted, resulting in malignant transformation. This phenomenon was named
      as a selective proliferation of cells.

PMID- 9275541
TI  - [Problems on the research on biological treatment of tumors].

PMID- 9275540
TI  - [Microsurgical anatomical study of the wall of the cavernous sinus].
AB  - OBJECTIVE: To observe the microanatomical structures of the wall of cavernous
      sinus (CS) in order to provide anatomical basis for direct microsurgical
      operation to the CS. METHODS: 48 aides of the CS of adult cadavers were dissected
      in detail under operative microscope. RESULTS: The CS was a narrow and long
      irregular hexahedron in shape. The supperior wall, the posterior wall and the
      superficial dural layer of the lateral wall of the CS were formed by internal
      layer of the cerebral dura. The deep layer of the interal wall was formed by the
      sheaths of nerves II, IV, V1, V2 with a reticular membrane between these sheaths.
      There was a superficial compartment between the superficial layer and deep layer
      of the lateral wall in 31.25% of the specimens. The inferior wall of the CS was
      intracranial periosteum. The medial wall was formed by stretched fibres from the
      tentorium of hypophysis. The anterior aspect was formed by the sphenoid sinus and
      the superior orbital fissure. Direct microsurgical approaches to the CS via the
      medial trangles of the superior wall and Parkinson tranales of the lateral wall
      were most important. CONCLUSION: A microanatomical structure of the wall of the
      CS is provided for direct microsurgical operation to the CS, and the direct
      microsurgical approaches are discussed.

PMID- 9275542
TI  - [Diagnostic and therapeutic errors in lung cancer].

PMID- 9275543
TI  - [Augmentation of liver immune functions by intrasplenic transplantation of IL-2
      gene-modified hepatocytes].
AB  - OBJECTIVE: To investigate the effects of intrasplenically transplanted, IL-2 gene
      modified hepatocytes on the liver immune response and anti-tumor activity.
      METHODS: Murine fetal hepatocytes BNL CL. 2 were transfected with mIL-2 gene in
      vitro, and intrasplenically transplanted into syngeneic mice (2 x 10(6)/mouse).
      After two weeks, the Kupffer cells were isolated and studied for cytotoxicity,
      TNF and NO production, and Ia expresson. The therapeutic effects on the mice with
      the metastatic liver carcinoma were also observed. RESULTS: The Kupffer's
      cytotoxicity to L1210, Yac-1, P815 and H22 target cells, and their production of
      TNF and NO were greatly augmented, even when freshly prepared. Their Ia
      expression also increased. When treated with IL-2 gene-modified hepatocytes, the
      metastatic liver carcinoma-bearing mice survived for a longer time. CONCLUSIONS:
      Intrasplenic transplantation of IL-2 gene-modified hepatocytes could effectively
      activate the liver immune response and exert potent therapeutic effects on liver
      carcinoma-bearing host.

PMID- 9275544
TI  - [The effect of antisense H-ras on growth and metastasis of a high metastatic
      tumor model of human hepatoma in nude mice LCI-D20].
AB  - OBJECTIVE: To investigate if treatment with antisense H-ras oligodeoxynucleotides
      (ODNs) modulates tumor growth, apoptosis and metastasis of a high metastatic
      tumor model of human hepatocellular carcinoma (HCC) in nude mice LCI-D20, in
      which over-expression of H-ras has been identified. METHODS: LCI-D20 cells in
      primary culture were treated with 10 mumol/L antisense ODNs in vitro. 1.5 x 10(6)
      LCI-D20 cells with or without pretreatment were inoculated into each elevated
      subcutaneous (s.c) flap in fourteen nude mice, 6 animals for antisense H-ras ODN
      treated cells, 4 for H-ras non-specific antisense ODN treated cells, the rest 4
      for cells without pretreatment. RESULTS: In in vitro cell culture study, 5-day
      continuous suppression of H-ras expression by antisense H-ras ODNs resulted in
      significant inhibition of the proliferation of LCI-D20 cells (t = 31.529, P <
      0.01). Cell cycle analysis showed a significant decrease in S phase (36.0 +/-
      1.4) and a remarkable increase in G1/G0 fraction (56.7 +/- 1.1) after exposure to
      antisense H-ras ODNs in comparison with the cells without any treatment (58.5 +/-
      0.9, t = 13.519, P < 0.01, 37.4 +/- 0.7, t = 14.802, P < 0.01). In situ end
      labeling (ISEL) detection showed that apoptotic cell death was significantly
      increased in cells with 5-day treatment of antisense H-ras ODNs (34.0% +/- 4.5%)
      in comparing with cells without treatment (2.5% +/- 1.2%, t = 13. 434, P < 0.01)
      or treated with non-specific antisense ODNs (4.8% +/- 1.4%, t = 12.453, P < 0.01)
      at the corresponding time. In in vivo experiment, after six-week observation,
      tumor growth in antisense H-ras treated animals was significantly retarded in
      comparison with that of the untreated (t = 3.509, P < 0.01) or nonspecific
      antisense ODN treated animals (t = 3.452, P < 0.01). CONCLUSIONS: Specific
      inhibition of H-ras expression by antisense H-ras ODNs could not only induce
      apoptotic cell death, inhibit the growth rate of LCI-D20 cells in vitro and in
      vivo, but also alter in vivo tumorigenesity and metastatic potential of LCI-D20
      cells.

PMID- 9275545
TI  - [Granulocyte-macrophage colony-stimulating factor (GM-CSF), preclinical and phase
      I clinical investigations].
AB  - OBJECTIVE: To conduct preclinical studies and phase I trial of the recombinant
      human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). METHODS:
      Pharmacodynamics, pharmacokinetic and toxicology of the rhGM-CSF were studied in
      animal models, and the safety was also evaluated in humans. RESULTS: The human
      bone marrow cells could be stimulated by purified rhGM-CSF to form multilineage
      colonies (CFU-GM and BFU-E). The rhGM-CSF administered for 7 days to Beagle dogs
      and monkeys subjected to 60Co r-ray irradiation was shown to induce both rapid
      and sustained increase in circulating leukocyte counts. Toxicology testing showed
      that the LD50 (i.v) was over 5000 micrograms/kg, and LD50 (i.p) over 10000
      micrograms/kg in mice. Administration of the rhGM-CSF in excess of four times as
      much as clinical dosages was not associated with severe chronic toxicities. Most
      injected rhGM-CSF was excreted from urine, and did not accumulate in the body. In
      the phase I clinical trial, injecting 2.5-7.5 micrograms/day of rhGM-CSF was
      safe. CONCLUSION: It is effective and safe to use rhGM-CSF in the treatment of
      leukocytopenia.

PMID- 9275546
TI  - [Human melanoma-specific peptide antigens recognized by HLA-A2 restricted tumor
      infiltrating lymphocytes].
AB  - OBJECTIVE: HLA-A2-associated peptides were extracted from human melanoma cell
      lines and used to study human melanoma-specific peptide antigens for HLA-A2
      restricted tumor-infiltrating lymphocyte (TIL). METHODS: TILS were derived from
      the peripheral lymph nodes of HLA-A2+ human melanoma patients, HLA-A2 molecules
      were purified from the melanoma cell lines by immunoaffinity column
      chromatography of detergent-solubilized cell pellets. Peptides bound to the HLA
      A2 molecules were acid eluted and fractionated by reversed phase RP-HPLC.
      Individual fractions were assessed for their ability to reconstitute melanoma
      specific epitopes by adding to the HLA-A2+ Ag-processing mutant cell, T2.
      RESULTS: These TIL lysed HLA-A2+ autologous and allogeneic melanomas, but not the
      HLA-A2- melanomas. They also did not lyse the HLA-A2+ non-melanoma cell lines.
      The RP-HPLC separations of reconstituting fractions revealed three peaks
      (fractions) of reconstitution. CONCLUSION: These results showed that peptides
      derived from three active fractions were related to human melanoma-specific
      peptide antigens recognized by HLA-A2-restricted TIL.

PMID- 9275547
TI  - [Molecular bypass, the application of VEGF to gene therapy of limb ischemia].
AB  - OBJECTIVE: To investigate the feasibility of using VEGF gene directly for
      treating limb ischemia. METHODS: The human VEGF165 cDNA was cloned into the
      eukaryotic expression vector pcDNA3 under the control of cytomegalovirus
      immediate-early promoter/enhancer. When gene suture was used, the recombinant
      plasmid was transferred into the hindlimb's adductor of rat, of which the distal
      extreme of external iliac artery was ligated and the femoral artery was
      completely excised. With RT-PCR, Western blot, immunohistochemistry analysis, and
      angiography, the expression and biological effects of VEGF gene in experimental
      animals were investigated. RESULTS: Seven days after initiation of therapy, the
      transcription and expression of VEGF gene in experimental group were
      significantly higher than those of control groups. The results from angiography,
      feet temperature measuring and observation of clinical symptom showed that the
      transfer of VEGF gene can stimulate the formation of focal neovessles, establish
      colleteral circulation, augment blood perfusion, and ameliorate distal limb
      necrosis. CONCLUSION: These findings reveal that the "molecular bypass" using
      VEGF gene may represent a potential therapeutic modality for treating tissue
      ischemia.

PMID- 9275548
TI  - [Overexpression of P53 and its risk factors in esophageal cancer in urban areas
      of Xian].
AB  - OBJECTIVE: To investigate the risk factors of esophageal cancer (EC) in urban
      areas of Xi'an, and to correlate these risk factors with overexpression of P53 in
      EC. METHODS: A hospital-based case-control study was performed. All cases (89)
      and controls (97) were permanent residents in urban areas of Xi'an. Tumor tissues
      and normal tissues adjacent to tumors of 65 cases, and 24 available normal
      esophageal tissues of controls were detected by P53 overexpression via
      immunohistochemical method. RESULTS: Smoking and family history of EC were
      significantly associated with EC in Xi'an inhabitants. OR was 3.26 and 10.48,
      respectively. The laboratory findings indicated that P53 positive stain in Ec was
      52.3% (34/65) and 6.1% (4/65) in normal tissues adjacent to tumor, but no
      positive stain was found in normal esophageal tissues of controls. Moreover, the
      results showed that P53 overexpression was closely related to smoking and family
      history of EC. OR was 3.89 and 17.28, respectively. CONCLUSION: These findings
      suggest that smoking and family history of EC are important risk factors for EC,
      and the alteration of P53 gene may be related to smoking and inherited factor.

PMID- 9275549
TI  - [Correlation of multiple gene changes with malignant phenotype of human gastric
      carcinoma].
AB  - OBJECTIVE: To investigate the alteration of oncogenes and tumor suppressor genes
      in gastric carcinogenesis. METHODS: Southern blot, PCR/SSCP and DNA sequencing
      techniques were used in 33 gastric carcinomas to detect c-met, EGFR, c-erbB-2,
      AKT-2, c-Ha-ras, p53, p16 and nm23-H1, for the presence of amplification,
      deletion, mutation and rearrangement. RESULTS: Most tumors (70%) haboured one or
      more altered genes. The number and type of gene alteration were different among
      individuals. Rearrangement of c-met was noted in 2/33 cases (6%), and
      amplification of c-met, c-erbB-2 and AKT-2 in 8/33 cases (24.2%), 1/33 cases (3%)
      and 2/18 cases (11%) respectively. Homozygous deletion of P16 was seen in 6/33
      cases (18%). Loss of heterozygousity was also noted in nm23-H1 5/17 (29%) and p53
      2/13 (16%). The mutation rate of p53 in exon 5-8 was 20/33 (61%). Point mutation
      of p53 was found at both early and advanced tumors. In contrast, amplification of
      oncogenes and loss of tumor suppressor genes were correlated with poorly
      differentiated and metastatic tumors. CONCLUSIONS: Gastric carcinogenesis is a
      gradually developed process, results from sequencial alteration of multigenes.
      The malignant phenotype is associated with the degree of genetic abnormality.

PMID- 9275550
TI  - [Aneurysmal bone cyst: imaging diagnosis and evaluation of therapeutic methods].
AB  - OBJECTIVE: To determine the imaging features and useful therapeutic methods of
      aneurysmal bone cyst (ABC). METHODS: The radiographs, CT, and MR scans of 82
      cases of pathologically proved ABC were retrospectively analyzed. Post
      therapeutic follow-up of 45 cases was carried out for 3 months to 24 years.
      RESULTS: Plain radiographs showed eccentric expansile osteolysis in most cases.
      Fluid-fluid level was seen in 21/27 cases on CT scans, and calcification or
      ossification in 11/27 cases. MR images showed a hypointense rim in 7/7 cases,
      multilocular hyperintense cysts with hypointense septae on T2WI in 6/7 cases, and
      fluid-fluid levels in 5/7 cases. CONCLUSION: CT and MR scans are superior to
      plain radiographs in the diagnosis of ABC in the osteolytic phase and in the
      axial skeleton. Curettage combined with bone graft surgery is the most effective
      therapeutic method for ABC of the extremities. Arterial embolization with or
      without surgery is valuble for the treatment of ABC arising from the axial
      skeleton.

PMID- 9275551
TI  - [Establishment of human ovarian cancer cisplatin resistant cell line COC1/DDP and
      its mechanism of resistance].
AB  - OBJECTIVE: To establish cisplatin (DDP)-resistant subline of human ovarian cancer
      and investigate the mechanism responsible for resistance to DDP. METHODS: A DDP
      resistant human ovarian adenocarcinoma cell subline (COC1/DDP) was developed by
      contineous stepwise selection in increasing concentration of DDP from the parent
      cell line COC1 in vitro. The multiple changes of biological properties in
      COC1/DDP cell line were determined. RESULTS: COC1/DDP cells were of 6.5-fold
      resistance to DDP and displayed significant cross-resistant with carplatin and
      mitomycin C, but still remained sensitive to 5-fluorouracil and adriamycin. As
      compared to the parent cells, in COC1/DDP cells: the doubling time was reduced by
      12.9%. Cellular content of DDP was diminished by more one half and the DNA
      interstrand cross-links (ISC) was lower than that of the sensitive cells.
      Evidence of P-glycoprotein overexpression was not shown in COC1 and COC1/DDP cell
      lines by means of immunohistochemical method. CONCLUSIONS: The primary factor
      causing COC1/DDP resistance to DDP is the reduction of intracellular platinum
      accumulation and DNA ISC formation. The resistance is not considered to be
      associated with the multidrug resistant and P-glycoprotein.

PMID- 9275552
TI  - [Mutation analysis of mitochondrial DNA of children with Rett syndrome].
AB  - OBJECTIVE: To identify whether mitochondrial DNA (mtDNA) mutation is involved in
      the pathogenesis of Rett syndrome (RS), we undertook a mutation analysis of the
      mtDNA genome. METHODS: mtDNA from 15 children with RS and 14 their mothers were
      analysed by using Southern hybridization, polymerase chain reaction (PCR), single
      strand conformation polymorphism (SSCP) and DNA direct sequencing. Total DNA was
      isolated from white blood cells. RESULTS: Southern hybridization with whole mtDNA
      probe revealed no large deletions in mtDNA. PCR amplification and SSCP analysis
      showed mutation(s) in the region 2650-3000 encoding 16SrRNA of mtDNA in 13 RS
      patients and 11 their mothers. DNA sequence analysis and mismatch PCR showed a
      point mutation (C-->T) at the position 2835 in 7 RS patients and 6 their mothers.
      The same mutation was not found in 30 normal controls. CONCLUSION: These data
      indicate that mtDNA may play a role in Rett syndrome.

PMID- 9275553
TI  - [Immunotactoid glomerulopathy].
AB  - OBJECTIVE: To describe 3 patients with immunotactoid glomerulopathy (IT) and
      their clinicopathological features. METHODS: Renal biopsies were examined by EM:
      they were collected during the last 3 years in Department of Nephrology, First
      Hospital of Beijing Medical University. The amyloidosis, fibrillary
      glomerulopathy (FGP) and other systemic disease were excepted by clinical
      analysis, LM, IF, Congo red staining and image pattern analysis. RESULTS: The
      ultrastructural characteristic of the three cases were microtubular fibrils
      (diameter: 35-47 nm) deposited in various sites of glomeruli (GBM, subendothelium
      and mesangium) and electron dense deposits. In addition, randomly fibrillary
      deposits (diameter: 20 nm) were also found. The fibrils were negative with Congo
      red staining. The 3 patients were young middle-aged men with proteinuria,
      microscopic hematuria and hypertension, two of them had renal insufficiency.
      CONCLUSIONS: IT is a rare nephropathy but exists in China. Our, patients, were
      younger Than reported and there prognosis were poor. The microtubular and
      fibrillary deposits appear in some cases, indicating that IT and FGP are
      different subtypes of an entity.

PMID- 9275554
TI  - [A time-course observation of influence of pemphigus autoantibody upon
      desomosome].
AB  - OBJECTIVE: To observe the time-course changes of desmosome and its dg2/3
      component in the process of acantholysis. METHOD: After setting up a pemphigus
      organ model and an acantholysis model by purified pemphigus autoantibody, the
      desmosome structures at light and electromicroscopic levels and desmoglycoprotein
      dg2/3 immunohistochemical stains were observed at different culture times.
      RESULTS: In pemphigus organ model and acantholysis model, pemphigus autoantibody
      only induced the increase of the intercellular space at 24 hour. Even at 48 hour,
      only a few desmosomes were damaged. But by 72 hour, the structures of desmosomes
      almost completely disappeared, and the cell membrane flattened.
      Immunohistochemical stains showed that there was an internalization of
      desmoglycoprotein dg2/3 at 48 and 72 hour during the process of acantholysis.
      CONCLUSION: Our results suggested that the influence of pemphigus autoantibody on
      desmosomes appears at a relative later stage, but the damage of desmosomes is a
      pivotal step to acantholysis.

PMID- 9275555
TI  - [The mechanisms of ET-1-induced lung edema].
AB  - OBJECTIVE: To investigate the machanisms of ET-1-induced lung edema. METHODS:
      Different doses of ET-1 were added to isolate rat lungs perfused by Ringer's
      solution containing albumin to explore the mechanisms of ET-1 induced pulmonary
      edema. The lung weight gain, pulmonary vascular permeability to water (Wf) and
      albumin (Ps) were observed. RESULTS: It was found that low dose ET-1 increased
      lung weight gain, pulmonary artery pressure, pulmonary capillary pressure,
      pulmonary vascular post-resistance and total resistance, but no significant
      changes of vascular permeability were observed. CONCLUSION: The mechanisms of
      lung edema induced by ET-1 are different. Low dose ET-1 may induce lung edema by
      increasing pulmonary vascular permeability while large dose ET-1 by increasing
      pulmonary vascular pressure.

PMID- 9275556
TI  - [The influence of hypoxia/reoxygenation on production and release of nitric oxide
      from cultured newborn rat cardiomyocytes].
AB  - OBJECTIVE: To study the influence of hypoxia/reoxygenation on the production and
      release of nitric oxide (NO), lactate dehydrogenase (LDH) and creatine kinase
      (CPK) from cultured newborn rat cardiomyocytes. METHODS: The rats were divided
      into four groups: control, hypoxia/reoxy-genation, heat shock pretreated,
      dexamethasone pretreated. RESULTS: After 3 hours of hypoxia and 30 minutes of
      reoxygenation, the content of NO in the supernatent of cardiomyocytes increased
      significantly (P < 0.05), which was accompanied by an increase in the release of
      LDH and CPK (P < 0.001, P < 0.001 respectively). When pretreated by the heat
      shock (exposed to 42 degrees C for 1 hour and then allowed to recover for 24
      hours) or by applying dexamethasone at the onset of hypoxia, the production and
      release of NO, LDH, CPK decreased markedly (P < 0.05). CONCLUSIONS: Excessive
      release of NO may play an important role in the reperfusion injury of
      cardiomyocytes. Heat shock seems to provide protection for cardiomyocytes from
      hypoxia/reoxygenation injury. The mechanism may be related to the inhibition of
      excessive release of No from the cardiomyocytes.

PMID- 9275557
TI  - [Advances in the research on relation between sex hormones and liver cancers].

PMID- 9275558
TI  - [Mismatch repair gene defects in large intestinal cancers].

PMID- 9275559
TI  - [Progresses of respiraology in China, 1996].

PMID- 9275560
TI  - [Progresses in cardiology in China, 1996].

PMID- 9275561
TI  - [Progresses in gastroenterology in China, 1996].

PMID- 9275562
TI  - [Progresses in hematology in China, 1996].

PMID- 9275563
TI  - [Progresses in diabetology in China, 1996].

PMID- 9275564
TI  - [Progresses in neurology in China, 1996].

PMID- 9275566
TI  - [Progresses in rheumatology in China, 1996].

PMID- 9275567
TI  - [Progresses in infections diseases in China, 1996].

PMID- 9275565
TI  - [Progresses of psychiatry in China, 1996].

PMID- 9275568
TI  - [Progresses in tuberculosis in China, 1996].

PMID- 9275569
TI  - [Progresses in tropical diseases and parasitosis in China, 1996].

PMID- 9275570
TI  - [Progresses in general surgery in China, 1996].

PMID- 9275571
TI  - [Progresses in neurosurgery in China, 1996].

PMID- 9275572
TI  - [Progresses in cardiovascular surgery in China, 1996].

PMID- 9275573
TI  - [Progresses in thoracic surgery in China, 1996].

PMID- 9275574
TI  - [Progresses in orthopedics in China, 1996].

PMID- 9275575
TI  - [Progresses in urology in China, 1996].

PMID- 9275576
TI  - [Progresses in pediatric surgery in China, 1996].

PMID- 9275578
TI  - [Progresses in burn surgery in China, 1996].

PMID- 9275577
TI  - [Progresses in microsurgery in China, 1996].

PMID- 9275579
TI  - [Progresses in organ transplantation in China, 1996].

PMID- 9275581
TI  - [Progresses in gynecology in China, 1996].

PMID- 9275580
TI  - [Progresses in anesthesiology in China, 1996].

PMID- 9275583
TI  - [Progresses in family planning in China, 1996].

PMID- 9275582
TI  - [Progresses in prenatal medicine in China, 1996].

PMID- 9275584
TI  - [Progresses in pediatrics in China, 1996].

PMID- 9275585
TI  - [Progresses in child health in China, 1996].

PMID- 9275586
TI  - [Progresses in andrology in China, 1996].

PMID- 9275587
TI  - [Progresses in emergency medicine in China, 1996].

PMID- 9275588
TI  - [Progresses in ophthalmology in China, 1996].

PMID- 9275589
TI  - [Progresses in otorhinolaryngology in China, 1996].

PMID- 9275590
TI  - [Progresses in stomatology in China, 1996].

PMID- 9275591
TI  - [Progresses in occupational diseases in China, 1996].

PMID- 9275592
TI  - [Progresses in dermatology and venerology in China, 1996].

PMID- 9275593
TI  - [Progress in the study of endemic diseases in China, 1996].

PMID- 9275594
TI  - [Progresses in laboratory medicine in China, 1996].

PMID- 9275595
TI  - [Progresses in ultrasonic medicine in China, 1996].

PMID- 9275596
TI  - [Progresses in radiology in China, 1996].

PMID- 9275597
TI  - [Progresses in laser medicine in China, 1996].

PMID- 9275598
TI  - [Progresses in nuclear medicine in China, 1996].

PMID- 9275599
TI  - [Progresses in clinical epidemiology in China, 1996].

PMID- 9275600
TI  - [Progresses in pathology in China, 1996].

PMID- 9275601
TI  - [Progresses in physiopathology in China, 1996].

PMID- 9275602
TI  - [Measurement and analysis of bone mineral density of lumbar vertebrae and
      alveolar bone in patients with periodontitis].
AB  - Periodontitis and osteoporosis are world-wide diseases. It has been suggested
      that periodontitis and osteoporosis might be related. In order to evaluate this
      possible relationship, the bone mineral density (BMD) of the lumbar vertebrae and
      alveolar bone in 21 patients with severe chronic periodontitis (CP), 11 patients
      with rapidly progressive periodontitis (RPP), and 14 normal persons was measured
      by dual photon absorptiometry. The results show: The alveolar BMD of
      periodontitis patients is significantly lower than normal persons. The lumbar
      vertebrae BMD has not significantly different between periodontitis patients and
      normal persons. The lumbar vertebrae BMD and alveolar BMD have not significantly
      different between CP and RPP. We therefore suggest that the alveolar BMD and
      lumbar vertebrae BMD have not relationship, the osteoporosis is not an important
      factor in the pathogenesis of periodontitis.

PMID- 9275603
TI  - [Substance P in synovial fluid in patients with temporomandibular joint
      dysfunction syndrome].
AB  - Radioimmunoassay technique was used to measure substance P levels in synovial
      fluid samples from thirty patients with temporomandibular joint dysfunction
      syndrome (TMJDS). Twenty-four samples (80%) were found to have substance P.
      Concentrations of substance P in the synovial fluid from patients with painful
      TMJDS were higher than those patients without pain (P < 0.05). The study
      supported the evidence for the secondary synovitis in painful TMJDS, and
      suggested that the nervous system play a role in the pathophysiology of TMJDS.

PMID- 9275604
TI  - [The effects of lipoteichoic acid and calcium on the adherence of oral
      streptococci in vitro].
AB  - In this study, the effects of lipoteichoic acid (LTA) and calcium on adherence of
      oral streptococci in vitro were investigated. The results revealed that the
      adherence of streptococcus sobrinus to a glass surface was increased by the
      addition of calcium, in the condition of the same calcium ion concentration, LTA
      inhibited adherence, suggesting that LTA and the bacterial cell surface LTA
      competed for the same site of calcium ion, providing some evidence to support
      calcium-bridging theory. The result also showed that calcium ion not only
      influenced sucrose-independent adherence, but also infulenced sucrose-dependent
      adherence. The effect of calcium ion on the adherence has a threshold, over which
      the adherence was reduced.

PMID- 9275605
TI  - [Dental appliances for the treatment of obstructive sleep apnea syndrome].
AB  - This study combined the use of cephalometrics and overnight polysomnographic
      monitoring to analyze the effects of a dental appliance on airway, sleep and
      respiratory conditions in 10 patients with obstructive sleep apnea. The findings
      indicated that horizontal and vertical mean changes in mandibular position while
      the appliance was worn were 1.73 mm and 9.30 mm, respectively, the mean superior
      airway space increased by 2.80 mm (P < 0.01), while the mean middle airway space
      increased by 6.75 mm (P = 0.01), the inferior airway space, however, didn't
      change significantly when the appliance was worn. The average Apnea Index
      decreased by 15.98 events per hour when the appliance was worn (P < 0.01), the
      average Respiratory Disturbance Index decreased from 39.43 to 6.62 events per
      hour in 9 of 10 patients (P < 0.01, one patient didn't have recording of
      hypoventilation). the lowest SaO2 value increased from 73.87% to 85.50% (P <
      0.01). The reduction in the rate of airway obstructive events is attributed to
      the effect of appliance on the orophargneal structures. The dental appliance is a
      conservative, successful treatment alternative that could benefit patients with
      obstructive sleep apnea syndrome.

PMID- 9275606
TI  - [Experimental study on the healing of immediate replanted tooth after using
      exogenous fibronectin].
AB  - The purpose of this article is to study the effect on the healing of immediate
      replanted teeth after the biological characters of roots were changed by using
      exogenous fibronectin (Fn). Two adult rhesus monkeys were chosen in the
      experiment. Upper-incisors of each monkey were extracted. The teeth of
      experimental group were extracted the roots treated by 0.5 mg/ml Fn solution and
      replanted immediately. The roots of another animal were used as controls. After
      operations, the experimental specimens of 4 weeks and 8 weeks were examed
      histologically by light microscope and studied quantitatively by computer image
      analysis system. The results reveal that Fn can enhance periodontal healing by
      improving periodontal reattachment and reducing root resorption of replanted
      tooth. Fn has also the function to reduce inflammatory reactions significantly
      during the healing process.

PMID- 9275607
TI  - [Effects of capsules on attachment of human periodontal ligament fibroblasts to
      root surface].
AB  - Inhibition of attachment of human periodontal ligament fibroblasts to root
      surface by three capsules were determined with the methods of trypan blue and
      L*a*b* color difference measurement. The results showed that capsule from
      porphyromonas gingivalis was the strongest one in inhibiting attachment and
      followed by the one from provotalla intermedia. Capsule from porphyromonas
      endodontolis was the weakest one. The values of color difference from that of
      control root surface were 11, 13, 8.28 and 4.09 respectively. Inhibitory
      mechanism of capsules may include a direct growth inhibition of fibroblasts and a
      decrease in attachment due to changes of root surface properties. There were a
      few fibroblasts attached to root surface with progressive periodontitis, this was
      a sharp contrast with that of control root surface. We deduce that long term
      affections of toxins including capsules and other substances led to changes of
      root surface with periodontitis, which made fibroblasts difficult to attach.

PMID- 9275608
TI  - [A comparison of the changes of the nasal deformities after cleft lip repair
      between rotation advancement and triangular flap repair].
AB  - 126 patients with the secondary nasal deformities of cleft lip were chosen at
      random, whose primary correction of cleft lip were performed by the same surgon.
      Of them, 68 patients were treated by triangular flap method, other 58 by rotation
      advancement method. On their photographs, two methods were compared by
      measurement of the distance between alar bases and median saggittal plane, the
      width of nostril floor, the height of the columella, the sizes of nostrils on
      both sides, and tilt of columella. The nasal deformities were improved in the
      rotation advancement group, but this method trend to result in a small nostril to
      make correction of secondary nasal deformities more difficult. On the other hand,
      the nasal defects were little improved in triangular flap group, whereas there
      were much less tendency to result in a small nostril.

PMID- 9275609
TI  - [Clinical and radiographic study of Sjogren syndrome in children].
AB  - Eight cases of Sjogren syndrome in children were presented. Recurrent swelling of
      salivary glands was shown to be predominant findings in children with Sjogren
      syndrome. It was first reported that "lace-like" appearance of main duct was of
      great value in sialographic diagnosis of Sjogren syndrome in children. The
      differentiation between Sjogren syndrome and recurrent parotitis in children was
      discussed.

PMID- 9275610
TI  - [Human mucoepidermoid carcinoma MEC-1 cells induced differentiation by HMBA].
AB  - Mucoepidermoid carcinoma is the most common malignant tumor of salivary glands.
      In this report, we used hexamethylene bisacetamide (HMBA) as a inducer to induce
      human mucoepidermoid carcinoma cell line MEC-1 cells to differentiate. The growth
      kinetics, morphological changes and DNA contents of the cells were investigated.
      The results showed that HMBA-treated MEC-1 cells tend to become mature cells,
      implying that HMBA can induce differentiation of MEC-1 cells in vitro.

PMID- 9275611
TI  - [Study on experimental cervical defect of human tooth by SEM].
AB  - Experimental cervical defects on 12 pairs of premolar caused by cross-brushing,
      erosion and occlusal force separately or together were observed under SEM Changes
      on the surface of cervical defects suggested that the defects were induced by the
      above three factors combined. It was interesting that various kinds of
      microcracks were noticed on sections of enamel and dentin at the cervical defect
      areas made by mimicking occlusal force combined with other factors. The results
      seemed to indicate that the occlusal force would play an important role on
      formation of the cervical wedge-shaped defect and that accumulation of the stress
      caused the hard tissue injured and microcracked.

PMID- 9275612
TI  - [Mandibular ridge augmentation with hydroxylapatite and its extension].
AB  - The results of 5 years follow-up of 84 cases of mandibular residual ridge
      augmented with hydroxlapatite (HA), followed by ridge extension, are reported.
      The first surgical procedures, subperiosteal HA insertion, and the second stage
      of total lowering of the floow of the mouth, vestibuloplasty and skin graft are
      detailedly described. The ridge is augmented by the first surgery, disturbance of
      the fraenums of the lip, buccal and tongue and muscles are eliminated by the
      second surgery, to increase denture retention and stability, improve wear
      resisting of tissue covered over the artifical ridge and eliminate pain and
      uncomfort when wearing denture. The results of five years follow-up show that two
      stages reconstruction are better than HA insertion only. HA is a kind of ideal
      material of bone replacement, which is not resorbed in most cases.

PMID- 9275613
TI  - [The electron microscopic observation of the effect of monoclonal antibody on the
      form and structure of mutans streptococci OMZ176].
AB  - The effect of monoclonal antibody on the form and structure of Mutans
      Streptococci OMZ176 was studied. The result showed that a great number of Mutans
      Streptococci OMZ176 was agglutianated after treating with monoclonal antibody
      prepared by a cell wall protein antigen (molecular weight 220 kd) of Mutans
      Streptococci OMZ176. Bacterial cells were swollen obviously. The gap between cell
      wall and cytoplasmic was widened. The electronic density of cell plasm was
      greatly decreased.

PMID- 9275614
TI  - [Multifactor analysis of predisposing factors of oral candidosis in adults].
AB  - To study the prodisposing factors of oral candidosis in adult, analyst statistic
      package (quantity theories II) were used for the multifactor regressive analysis
      on 116 cases with oral candidosis and 76 gender and age matched normal controls.
      Six possible predisposing factors including gender, smoke, job, denture, drug
      use, systemic and other mucosal disease accompanied were inquired. The results
      showed that the most active predisposing factors were systemic or other oral
      mucosa disease accompanied, which include post-operative states, post
      radiotherapy states, Sjogren's syndrome; followed by drug use before onset of
      oral candidosis, especially topic antibiotics; the four other factors (smoke,
      job, denture and gender) have some effect but do not play any conclusive role on
      the occurence of oral candidosis.

PMID- 9275615
TI  - [Reconstruction of TMJ condyle cartilage defects with autogenous free periosteal
      grafts].
AB  - How to reconstruct the damaged articular cartilage has been one of the main
      subjects in treatment of articular disease for a long time. In this experimental
      study, fullthickness cartilage defects of 4 mm x 5 mm in size were created in
      rabbit's TMJ condyle cartiage on the left sides. The autogenous free periosteum
      were transplanted to the defects by using biological gelatin. Postoperatively,
      the animals were killed at intervals of 1, 2, 4, 8, 12 and 16 weeks. The
      regenerative cartilage in the defects were examined by gross appearance and
      histology. The result showed that mesenchymal cells in the cambium layer of
      periostum can transform into chondroblasts under the mechanical stress.

PMID- 9275616
TI  - [Investigation of infiltrating lymphocytes and immunoglobulin by
      immunohistochemical method in cheilitis granulomatosa].
AB  - Category and distribution of infiltrating lymphocytes and immunoglobulin in 12
      cases with cheilitis granulomatosa (CG) and 4 cases with Melkersson-Rosenthal
      syndrome (MRS) were investigated. The result was that infiltration of lymphocytes
      in granulomatous type was more severe than that in interstitial inflammtion type.
      Infiltrators mainly consisted of T helper lymphocytes and immunoglobulin was IgM.
      It was considered that local immunoreaction was enhanced suggesting that cyto
      immunity was a dominant factor with participation of humoral immunity. The result
      will be helpful to elucidate the pathogeneses and the function of many immuno
      factors in the CG. It helps to understand the clinical manifestations and may be
      a theoretic reference for seeking immuno-modulation for treatment.

PMID- 9275617
TI  - [In vitro culture of neonatal mouse calvaria as a model for study of bone
      resorption].
AB  - We established the in vitro culture system of neonatal mouse calvaria. Bone
      resorption was determined by the following examinations; (1) the release of
      calcium from the calvaria into the medium was measured by use of atomic
      absorption spectrophotometer, and the treated to control ratio was calculated and
      used as an index of bone resorption; (2) the concentration of osteocalcin in the
      cultured medium was determined by radioimmunoassay; (3) histological examination.
      By combined use of the examinations, we were able to objectively determine the
      bone resorption of cultured calvaria.

PMID- 9275618
TI  - [Constant composition study on kinetics of enamel demineralization].
AB  - The aim of this work was to investigate the kinetic behaviour of whole enamel
      demineralization compared with that of powder enamel. Constant composition
      technique was used to maintain a constant undersaturation degree with respect to
      hydroxyapatite in the demineralizing solutions. The demineralizing processes were
      monitored by recording the volume of adding titrant solution. Finally, sections
      were measured for lesion depth by microradiography, and blocks were tested for
      microhardness. The results showed that demineralization of enamel powder nearly
      completed within 40 minutes, while demineralization of whole enamel was much
      slower and with a constant rate within the experimental time. It was also found
      there were significant increases of concentrations of calcium and phosphate in
      solutions during the first 40 hours of whole enamel demineralization. It suggests
      that the kinetic behaviour of whole enamel demineralization is different from
      that of powder enamel, which is not only due to the unique transport process in
      whole tissue, but also possible due to a different phase transformation before
      and after formation of a surface layer.

PMID- 9275619
TI  - [Algogenic substances and craniomandibular disorders].

PMID- 9275620
TI  - [The investigation of the renal modulating effect on body fluid in hypertension].

PMID- 9275621
TI  - [How to evaluate the iron therapy].

PMID- 9275622
TI  - [Changes in urinary excretion of platelet activating factor and its significance
      in patients with primary nephrotic syndrome].
AB  - In order to explore the change of urinary excretion of platelet activating factor
      (PAF) and its significance in patients with primary nephrotic syndrome (PNS), we
      determined the urinary and plasma PAF in 12 cases of PNS, using platelet
      aggregation bioassay. The results showed that the level of urinary PAF was
      significantly higher in patients with PNS (n = 12) than in healthy controls (n =
      10), but that of plasma PAF was comparable in patients with PNS and controls,
      suggesting that the excessive generation of PAF is confined to kidney. There was
      a significant positive correlation between urinary excretion of PAF and
      proteinuria (r = 0.73, P < 0.01). The results indicated that increased urinary
      excretion of PAF can serve as an indicator for augmentation of the permeability
      of glomerular basement membrane (GBM) in PNS.

PMID- 9275623
TI  - [Effects of changes of plasma motilin level on the motility of gallbladder in
      patients with chronic renal failure].
AB  - In order to study the relationship between plasma motilin and motility of
      gallbladder in patients with chronic renal failure (CRF). Gallbladder volumes
      were determined with ultrasound in 17 normal subjects and 22 patients with CRF.
      Fasting gallbladder volumes (FGVs) and postprandial residual gallbladder volumes
      in patients with CRF were much smaller than those of normal subjects (P < 0.01, P
      < 0.01). There was no significant difference of maximal percentage emptying of
      gallbladder between normal subjects and patients with CRF (P > 0.05). In 17
      normal subjects oral erythromycin administration reduce FGVs and postprandial
      residual gallbladder volumes (P < 0.05, P < 0.05). In 22 patients with CRF oral
      erythromycin administration changed neither FGVs nor postprandial residual
      gallbladder volumes. Radioimmunoassay was employed to measure plasma motilin
      concentration. The results showed that mean level of plasma motilin of patients
      with CRF was much higher than that of normal subjects (P < 0.01). There was
      sighificant negative correlation between plasma motilin level and FGVs. It is
      suggested that hypermotilinemia may be one of the major reasons for motility
      disorder of gallbladder in patients with CRF.

PMID- 9275624
TI  - [Effects of high dose pulse oral calcitriol on secondary hyperparathyroidism in
      patients with end-stage renal disease].
AB  - To evaluate the therapeutic effects of high dose pulse oral calcitrol, 3.5
      micrograms calcitrol three times a week and calcium carbonate were administered
      to 13 patients with end-stage renal disease on chronic hemodialysis with
      hyperparathyroidism refractory to conventional calcitrol therapy. Serum
      parathyroid hormone and osteocalcin were detected by radioimmunoassay. Serum
      parathyroid hormone level of the patients decreased from 1111 +/- 344 ng/L to 492
      +/- 218 ng/L by 57.5 +/- 11.5 percent (P < 0.01) in 6 months after the beginning
      of treatment. Both serum alkaline phosphatase and osteocalcin levels declined
      markedly, and correlated positively with that of parathyroid hormone. Plasma
      calcium concentration was markedly elevated, but no obvious increase of plasma
      phosphate was found. High dose pulse oral calcitrol was effective on secondary
      hyperparathyroidism. During the course of treatment timely and individual
      adjustment of calcitrol dose and dialysate calcium concentration is essential.

PMID- 9275625
TI  - [Effects of epidermal growth factor (EGF) on proliferation of human peritoneal
      mesothelial cells].
AB  - In order to study the effects of epidermal growth factor (EGF) on proliferation
      of human peritoneal mesothelial cells (HMC) and repair repair of damaged human
      peritoneum, the mesothelial cells from human omentum were seperated and cultured
      in vitro. The authors assessed the expression of EGF-R on the surface of HMC with
      ABC immune histochemical method and tested the proliferation extent of HMC
      treated with EGF at different time and dosage levels with 3H-thymidine
      incorporation method. The results showed that EGF-R existed on the surface of HMC
      and EGF could stimulate the proliferation of HMC. The proliferation of HMC
      growing in the media containing 20 micrograms/L EGF was more significant than
      that growing in RPMI-1640 alone. The greatest proliferation index (PI = 8.16) of
      HMC appeared in the media containing 50 micrograms/L EGF. The proliferation of
      HMC stimulated by EGF was time- and dose-dependent. These studies indicate that
      the proliferation of HMC stimulated by EGF may play a very important role in the
      structral and functional recovery of the injured peritoneum.

PMID- 9275626
TI  - [Inhibition of hepatitis B virus replication in vitro by phosphorothioate and
      tetradecyl phosphorothioate analogs of antisense oligonucleotide directed against
      precore and core regions].
AB  - In order to study the action of antisense oligonucleotide (ASON) against
      hepatitis B virus (HBV), the 2.2.15 cells were chosen as an in vitro cell culture
      assay system and phosphorothioate (PS) and tetradecyl PS analogs of a 16-mer ASON
      were synthesized against precore and core regions of HBV gene. ASONs could
      inhibit specifically 92%-95% of the HBsAg and 84%-87% of the HBeAg produced at a
      concentration of 10 mumol/L and depress the amount of HBV DNA in culture
      supernatant and cells. ASONs had no effect on cellular alpha-fetoprotein
      synthesis and no cytotoxicity. There was not any inhibitory effect on the
      expression of viral proteins with an unrelated oligonucleotide. At similar
      concentration, the tetradecyl PS ASON of the same length and sequence as PS ASON
      had a greater inhibitory effect and better permeation efficiency, so it seems to
      be a very promising drug to be developed.

PMID- 9275627
TI  - [Prevention of endotoxic shock in rats with hepatic stimulating substance].
AB  - In order to understand the mechanism of prevention of endotoxic shock and
      evaluate the pathological changes taking place, an animal model of endotoxic
      shock was established by intravenous injection of endotoxin into rats, which were
      then treated with a hepatic stimulating substance, hepatopoietin (HPN). The
      results were as follows; (1) There was coincidence of low blood pressure and high
      serum level of tumor necrosis factor (TNF) in the experimental rats. (2)
      Simultaneous intravenous injection of endotoxin and introperitoneal injection of
      HPN showed that HPN can prevent the drop of blood pressure, lower the TNF level
      and ameliorate the tissure injury in lungs and kidneys induced by endotoxin. If
      HPN was given 15 minutes ofter injection of endotoxin, the drop of blood pressure
      could not be prevented and the TNF level remained high. It is suggested that TNF
      is an important mediator for endotoxic shock and treatment of endotoxic shock
      might be effective, if it is intituted early.

PMID- 9275628
TI  - [Relationship between heart rate variability and clinical features and prognosis
      of acute myocardial infarction].
AB  - Heart rate variability (HRV) was studied prospectively in 118 consecutive
      patients with acute myocardial infarction (AMI). HRV in AMI patients was
      significantly lower than that in normal controls, both at the 19th hour and the
      end of the 3rd week after the onset of AMI. Moreover, HRV at the end of 3rd week
      HRV in patients with cardiac death was also lower than that in the survivals.
      Measurements of ultra-low frequency power, total frequency power, very low
      frequency power, and the average of the standard deviation of every 5-minute
      period were independent predictors of cardiac death. All these 4 measurements
      have highly significant correlation (P < 0.01) and are better predictors of
      prognosis than other clinical variables. It is revealed that HRV at the end of
      3rd week after the onset of AMI has much greater prognostic value than that at
      the initial period.

PMID- 9275629
TI  - [A comparative study on coronary angiography and exercise ECG testing].
AB  - Both coronary angiography and exercise ECG testing were done in 461 patients. The
      comparative study showed that positive results of exercise ECG testing down-slope
      or horizontal depression of ST segment more than 0.1 mV during or after exercise
      may predict coronary artery disease, the sensitivity was 74.5% (322 cases) and
      specificity 84.2% (139 cases). With the use of ST depression more than 0.2 mV as
      the super-positive standard, the sensitivity and specificity of positive exercise
      ECG testing to predict triple vessel disease and left main coronary disease was
      61.3% and 79.1%, respectively. The workload and the increment of systolic blood
      pressure had a negative correlation (r = -0.4531 and -0.3), but the duration of
      ST depression had a positive correlation (r = 0.4502) with the number of diseased
      coronary arteries. The patients with multi-vessel disease and left main coronary
      artery disease had a higher positive rate of exercise ECG testing as compared
      with the patients with single or double vessel disease. The female patients had a
      higher false positive rate than the male. It is concluded that exercise ECG
      testing has some value in diagnosing coronary artery disease and predicting its
      severity. Some parameters in exercise is helpful to predict the severity of
      coronary artery disease.

PMID- 9275630
TI  - [Mechanism of plasma endothelin-1 level elevation and its relation with pulmonary
      hypertension in chronic cor pulmonale].
AB  - To explore the mechanism of plasma endothelin-1 (ET-1) level elevation and its
      relation with pulmonary hypertension in chronic cor pulmonale, plasma ET-1 level
      was measured by using radioimmunoassay in 21 cases of chronic cor pulmonale with
      acute exacerbation and cardiac catheterization was performed simultaneously.
      Results, Peripheral venous plasma ET-1 level of the patients was significantly
      higher than that of controls and also higher than that of peripheral arterial and
      pulmonary arterial plasma ET-1 level of the patients themselves. The plasma ET-1
      level of patients had a significant negative correlation with PaO2 and SaO2 and
      positive correlation with mean pulmonary arterial pressure (PAPM) and pulmonary
      vascular resistance index (PVRI). 9 of the patients were treated with mechanical
      ventilation. After ventilation, PaO2 went up notably and plasma ET-1 level
      decreased remarkably, PAPM and PVRI also reduced simultaneously. CONCLUSIONS: The
      causes of plasma ET-1 level elevation in cor pulmonale may be as follows,
      Firstly, pulmonary alveolar hypoxia increases the release of ET-1 in lungs;
      Secondly, the ability of the lungs to clean ET-1 decreases because of pulmonary
      abnormality. High level of plasma ET-1 may induce pulmonary hypertension. The
      level of plasma ET-1 can be lowered by correcting hypoxic status of the patients
      and the resulting improvement of pulmonary hemodynamics.

PMID- 9275631
TI  - [Preliminary diagnostic criteria for primary Sjogren's syndrome in China].
AB  - Primary Sjogren's syndrome (pSS) is a common autoimmune connective tissue disease
      in China yet without a universally accepted diagnostic criteria. In this study a
      new criteria was proposed and compared with other six sets of criteria. Fifty
      five items in 112 pSS and 185 controls were evaluated. Results show the criteria
      we proposed contained one major and nine minor items. For the purpose of
      identifying patients in clinical studies, a major with at least three of the nine
      minor items or at least five of the minor items should be presented. The major
      item is anti-SSA/SSB(+) and the minors are, (1) dry eyes or dry mouth (> 3
      months, persistently), (2) swollen salivary glands (recurrently or persistently),
      (3) rampant dental caries, (4) Schirmer test (< 5 mm in 5 min.) or corneal
      staining(+), (5) unstimulated salivary flow (< 0.03 ml/min) or abornal parotid
      sialography, (6) minor salivary gland biopsy (> or = 1 focus), (7) renal tubular
      acidosis, (8) hypergammaglobuminemia (gamma globulin > or = 30%) or
      hypergammaglobuminemic purpura, (9) RF > 1 : 20 or ANA > 1 : 20. Other connective
      tissure diseases, pre-existing lymphoma, AIDS, sarcoidosis, graft vs host disease
      must be excluded. The criteria we proposed had a high specificity of 98.2% and
      sensitivity of 94.1%.

PMID- 9275633
TI  - [Inherited thrombophilia].

PMID- 9275632
TI  - [Advances in the research on immunoglobulin A nephropathy].

PMID- 9275634
TI  - [Changes in the treatment of peptic ulcer].

PMID- 9275635
TI  - [Reconsideration of the endoscopic diagnosis of gastritis].

PMID- 9275636
TI  - [Antiphospholipid syndrome: a syndrome with re-recognition].

PMID- 9275637
TI  - [Serodiagnosis of Helicobacter pylori infections by detection of immunoglobulin G
      antibodies with an immunoblot technique].
AB  - Serological testing has recently been proposed as an aid in diagnosis of H.
      pylori infections. In this study, an immunoblot method has been evaluated to
      diagnose H. pylori infection serologically by comparing 104 serum specimens from
      patients with a positive Gram stain and/or culture result and a positive urease
      test on biopsy material, as well as 30 serum specimens from patients with
      negative urease test, and negative microscopy and culture results. Thirteen bands
      could be identified by immunoblotting and were found significantly more frequent
      in patients with H. pylori infections than in patients without such infections. A
      semiquantitative grading system was introduced with score 1 for each reactive
      band and score 1/2 for a weakly reactive band. If score 2 was the cut-off value
      for IgG antibody, then the sensitivity, specificity, positive predictive value
      and negative predictive value of the immunoblot test were 100.0%, 90.0%, 97.2%
      and 100.0% respectively. There was no marked cross reaction with both
      Campylobacter jejuni and Campylobacter coli.

PMID- 9275638
TI  - [Teprenone in the treatment of chronic superficial gastritis, a multicentre
      study].
AB  - Teprenone (Selbex), a gastric mucosal protective drug for treatment of chronic
      gastritis and gastric ulcer, has recently been used in the People's Republic of
      China. Teprenone in the treatment of chronic superficial gastritis (CSG): a
      surveillance study was recently conducted in 4 major hospitals in Beijing. The
      study included 98 patients (teprenone group 53 patients, Merzulene-S group 45
      patients) with endoscopically proven gastritis. The study showed that teprenone
      may relieve symptoms of CSG in 8 weeks. The effectiveness rate for flatulence was
      90.9% and for epigastralgia 87.2%. The improvement rate for the chronic
      inflammation in histopathology was 39.6% and disappearance rate for the activity
      of inflammation was 13.9%. It raised significantly the aminohexose level in
      gastric mucosa (P < 0.05) and increased gastric mucosal blood flow in gastric
      antrum (P < 0.05). These data suggest that teprenone is a safe and effective
      gastric mucosal protective drug.

PMID- 9275639
TI  - [Effects of Radix angelicae sinensis on systemic and portal hemodynamics in
      cirrhotics with portal hypertension].
AB  - The present study investigated effects of Radix angelicae sinensis (RAS) on
      systemic and portal hemodynamics in cirrhotic patients with portal hypertension.
      The results demonstrated that, after intravenous injection of the agent (20 mg.kg
      1.min-1), systemic hemodynamics (heart rate, mean arterial pressure, inferior
      vena cava pressure, systemic vascular resistance, cardiac output, cardiac index)
      remained unchanged, but portal hemodynamics signicantly improved, wedged hepatic
      venous pressure (WHVP) (3.79 +/- 0.76 kPa vs 2.72 +/- 0.89 kPa, P < 0.01) and
      hepatic venous pressure gradient (HVPG) (2.88 +/- 0.73 kPa vs 1.78 +/- 0.68 kPa,
      P < 0.01) reduced by 29.40 and 35.78 percent respectively. However, anti-portal
      hypertensive effect of RAS was inverse proportion to the basical level of WHVP or
      HVPG in the cirrhotics. We conclude that RAS can effectively decrease portal
      pressure and yet gives no influence on systemic hemodynamics in the cirrhotic
      patients with portal hypertension.

PMID- 9275640
TI  - [Study on some susceptible genes of systemic lupus erythematosus in Han
      nationality of China].
AB  - In order to explore the allelic polymorphism of HLA-DR and TNF B loci and
      susceptibility to systemic lupus erythematosus (SLE) in the Han nationality of
      northern China with the aid of methods of polymerase chain reaction/sequence
      specific primers (PCR/SSP) and polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) respectively. The findings from a case-control
      study on 151 blood samples (45 from the cases and 106 from the controls)
      indicated that there were significantly higher frequency of DR2 (P < 0.05, RR =
      1.56) and DR3 (P < 0.01, RR = 2.69), which represent candidate susceptible genes
      or useful markers for SLE. The DR5 allele in the samples (P < 0.05, RR = 0.43)
      might be an antagonistic or protective allele, or a marker for such allele. The
      frequency of TNF B * 1 and TNF B * 2 alleles was investigated in 45 SLE patients
      and 80 healthy controls and it was found that the frequency of TNF B * 2 allele
      was significantly higher in the patient group (P < 0.05, RR = 1.84). It might
      also be a suspicious susceptible allele or a marker for such allele. The
      frequency of HLA polymorphisms in various clinical/immunological subsets of our
      patient population was also determined. Clinical findings used include plasma
      SC5b-9 level, SSA, SSB, Sm, RNP, ANA antibodies, and SLE complications (SLE
      nephritis, pneumonia & encephalopathy). It turned out that there was a positive
      association between HLA-DR2 allele and SLE nephritis (P < 0.05, RR = 1.32).

PMID- 9275642
TI  - [The prevalence and risk factors of carotid atherosclerosis in elderly patients].
AB  - To assess the prevalence of extracranial carotid artery atherosclerosis and its
      relation to principal cardiovascular risk factors in Chinese elderly patients,
      100 cases aged from 54 to 94 were investigated with B-mode ultrasonography.
      Arterial intima-media thickening, plaque, mild stenosis (defined as a plaque that
      obstructed > 20% of the lumen diameter), and clinically significant stenosis (>
      50% in cross-sectional area) were found in 79, 49, 40 and 3 patients,
      respectively. There was no significant correlation between carotid
      atherosclerosis and coronary heart disease, cerebral infarction, hypertension,
      hyperlipidemia or diabetes. In contrast, the prevalence of carotid
      atherosclerosis was increased with age (P < 0.05), so did the severity. Thus, age
      is a major risk factor for carotid atherosclerosis in the elderly.

PMID- 9275641
TI  - [Accelerated streptokinase dose regimens for coronary thrombolysis].
AB  - Forty patients entering our hospital up to 12 hours (5.1 +/- 2.8 hours) after the
      onset of definite acute myocardial infarction were treated with accelerated
      streptokinase dose regimens (1.5 million U/30 min) intravenously. The reperfusion
      rate of infarct-related arteries determined by clinical evidence of reperfusion
      was 77.5% (31/40). There was significant difference in reperfusion rates: 89.3%
      (25/28) among patients within 6 hours versus 50% (6/12) among patients within 6
      12 hours after the onset of chest pain. Five cases (12.5%) experienced mild
      bleeding complications. One patient had chill. Three patients (7.5%) had
      hypotension (BP < or = 10.7/6.67 kPa, 1 kPa = 7.5 mmHg). The 5 week mortality was
      2.5% (1/40). In conclusion, intravenous accelerated streptokinase dose regimen
      for coronary thrombolysis seems to improve reperfusion rate markedly without
      increasing adverse events such as allergic reactions, severe bleeding and
      hypotension.

PMID- 9275643
TI  - [The effect of tumor necrosis factor alpha on hepatic necrosis in viral
      hepatitis].
AB  - In order to investigate the effect of tumor necrosis factor alpha (TNF alpha) on
      hepatocyte necrosis in viral hepatitis, TNF alpha with or without D-galactosamine
      (D-Gal) was injected into the abdominal cavity of rats. No effect was observed
      after injection of TNF alpha alone. After injection of TNF alpha with D-Gal, the
      total bilirubin level in rat blood increased and hepatocyte necrosis appeared (P
      < 0.05). Moreover, anti-TNF alpha McAb blocked the effect of hepatocyte necrosis
      produced by D-Gal and lipopolysaccharide (LPS). 130 samples of hepatic tissue
      were stained with anti-TNF alpha McAb by using ABC immunohistochemistry method.
      It was found that more severe the hepatocyte necrosis, more the positive cells
      expressing TNF alpha. There were more TNF alpha positive cells in the tissue of
      severe hepatitis. These results suggested that TNF alpha is a mediator in
      hepatocyte necrosis.

PMID- 9275644
TI  - [The effect of interferon in combination with ribavirin on the plus and minus
      strands of hepatitis C virus RNA in patients with hepatitis].
AB  - The effect of interferon in combination with ribavirin on the plus and minus
      strands of hepatitis C virus (HCV) RNA in patients with chronic hepatitis C (CHC)
      was studied by means of nested RT-PCR. The results showed that in those who
      respond to the combination of antiviral therapy, their increased serum ALT levels
      decreased to normal range, but more than half (55.56%) of these patients relapsed
      24 weeks after cessation of the antiviral therapy. The positive rate of the plus
      strand HCV RNA in serum (92.31%) decreased significantly to 38.46% (P < 0.005)
      and that of the minus strands HCV RNA in peripheral blood mononuclear cells
      (PBMC, 76.92%) to 38.46% (P < 0.05) at the end of the treatment, but little
      effect on the plus strand HCV RNA in PBMC in these patients was found. Relapse
      occurred in patients whose plus and minus strands of HCV RNA in PBMC remained
      positive during treatment. These data indicated that absence of HCV RNA in serum
      do not mean complete clearance of HCV and can not predict a sustained therapeutic
      response. For evaluating the antiviral effect and prognosis it is essential to
      measure the plus and minus strands of HCV RNA in serum and PBMC simultaneously.
      The results of the combined antiviral therapy were similar to that of single
      interferon treatment; it seems that rib-a-virin do not enhance the antiviral
      effect of interferon.

PMID- 9275645
TI  - [The causes, diagnosis and treatment of aluminum toxicity in patients with
      chronic renal failure undergoing dialysis].
AB  - To study the causes, diagnosis and treatment of aluminum toxicity in patients
      with chronic renal failure, the serum aluminum concentration was determined in 27
      normal subjects, 28 patients of various kinds of diseases with normal renal
      function and 81 patients of chronic renal failure with hemodialysis in 65 and
      without in 16, of whom 41 patients were determined the aluminum concentration in
      the bone tissue. Clinical symptoms were carefully observed in all patients and
      desferrioxamine (DFO) test was performed in 17 patients, of whom 10 were treated
      with DFO. The results showed that treatment with improperly processed water and
      administration of aluminum compound were the major causes of aluminum toxicity in
      uremic patients. Aluminum toxicity may induce anemia, encephalopathy and bone
      disease, but its clinical features were nonspecific and the diagnosis may require
      several serum aluminum determinations or DFO test. DFO can chelate aluminum in a
      variety of tissues so that the latter may be released into the blood circulation.
      The DFO test may be used to assess the actual aluminum load in the bone tissue.
      The changes in serum aluminum concentration after intravenous infusion of DFO
      correlated closely with bone aluminum level, suggesting that the DFO test may be
      useful for the diagnosis of aluminum toxicity. The DFO therapy may be indicated
      for, 1, patients with uremia having hyperaluminumnemia due to treatment with
      improperly processed water and intake of aluminum-containing agents. 2. those who
      had serum aluminum concentration of higher than 200 micrograms/L and positive DFO
      test and 3. patients whose aluminum concentration in the bone tissue was 10 times
      greater than normal values. In this study, DFO was given intravenously in a dose
      of 20-40 mg/kg, twice a week. Satisfactory results were obtained in 3 to 6 months
      and there were no severe side effects when the agent was administered slowly.

PMID- 9275646
TI  - [Obesity-hypoventilation syndrome].
AB  - 5 cases with obesity-hypoventilaion syndrome were reported. The clinical
      manifestations were obesity, palpitation, dyspnea, lethargy, cyanosis, distention
      of cervical vein, edema, enlargement of liver and hypertension. All of them were
      initially diagnosed as chronic bronchitis or heart diseases. Pulmonary function
      test showed restrictive ventilative defect and hypercapnia with hypoxemia. Mouth
      oclusion pressure at 0.1 second was higher than the normal value. The response to
      CO2 was decreased. Hypertrophy of right heart was shown in ECG and X-ray film
      improvement in symptoms and blood gases analyses were found to be associated with
      body weight decrease in a follow up period of one year.

PMID- 9275647
TI  - [Role and significance of leukotrienes in liver diseases].

PMID- 9275648
TI  - [Prolactin and autoimmune diseases].

PMID- 9275649
TI  - [Improving further the diagnosis and research standard of prostate carcinoma].

PMID- 9275650
TI  - [The application of high molecular weight cytokeratin in differential diagnosis
      of prostate adenocarcinoma].
AB  - In order to understand the characteristics of proliferative and malignant
      prostate lesions and to improve the differential diagnosis, immunohistochemical
      methods using high molecular weight cytokeratin monoclonal antibody 34BE12 to
      stain the basal cells and to differentiate prostate cancer from hyperplasia in 82
      prostate biopsies and specimens, which included 21 adenocarcinoma, 30
      intraepithelial neoplasia, 5 atypical adenomatous hyperplasia, 8 basal cell
      hyperplasia, 11 atrophy of prostate, 4 postatrophic hyperplasia and 3 cribriform
      hyperplasia. It was demonstrated that the basal cell layer was lost in all
      prostate adenocarcinomas, but existed in most of the proliferative lesions except
      for atypical adenomatous hyperplasia and grade 3 intra-epithelial neoplasia in
      which the basal layer was disrupted in some cases. The study showed that the
      34BE12 antibody was useful in the differential diagnosis of prostate
      adenocarcinoma.

PMID- 9275651
TI  - [Detection and clinical pathological significance of the expression of P21, P185,
      p53 proteins and mutation of ras, p53 genes in transitional cell carcinoma of the
      bladder].
AB  - In order to find the significance of gene changes in the development of
      transitional cell carcinoma of bladder, immunohistochemical and PCR-RFLP methods
      were used to study the expression of P21, P185, p53 proteins and mutations in ras
      and p53 genes. The results showed that the P21, P185 and p53 positive rates were
      59.3%, 55.3% and 29.3% respectively. Positive rates for P21 and P185 decreased
      with the progression of the pathological grade (P < 0.05). p53 positive rates
      decreased with the progression of pathological grade (P < 0.01). Positive
      expression of P21, P53 were significantly correlated with prognosis. Expression
      of more than two kinds of oncogene proteins were present in 73 cases of bladder
      transitional cell carcinoma. The rate of point mutation in codon 12 of Ha-ras
      gene of bladder transitional cell carcinoma was 32%. The p53 gene mutation rate
      of bladder transitional cell carcinoma was 18%, all mutations occurred at codon
      248. The point mutation in codon 12 of Ha-ras gene increased with the progression
      of pathological grade (P < 0.05). The ras and p53 gene mutations were
      significantly correlated with prognosis (P < 0.05). The mortality of patients
      with ras and p53 gene mutation were higher than patients without mutations. 4
      cases of bladder transitional cell carcinoma contained both ras and p53 gene
      mutations.

PMID- 9275652
TI  - [Interrelationship between endothelin and glomerular mesangial cells].
AB  - The interrelationship between endothelin (ET), endothelin receptors (ET-R) and
      glomerular mesangial cells (MC) was investigated by MC culture, RT-PCR, Northern
      blot hybridization, DNA cytometry and immunohistochemistry methods. The results
      showed that in MC, there existed the expression of ET mRNA and also the
      expression of 2 subsets ETA mRNA and ETB mRNA. ET mRNA peptide is synthesized in
      MC. ET mRNA induced significant MC contraction and stimulated MC division and
      proliferation. The results suggest that MC are special cells with the capacity of
      producing ET and are also the target cells for ET. It is possible that ET
      influence glomerular filtration area and rate by inducing MC contraction and
      cause also MC proliferation and glomerular sclerosis.

PMID- 9275653
TI  - [Expression of receptor-associated protein of the Heymann nephritis pathogenic
      epitope in Escherichia coli].
AB  - To study the pathological phenotype of pathogen and the mechanism of the
      immunocomplex in Heymann nephritis, we utilised DNA recombinant technique, to
      construct plasmid pGEX-R93 by inserting the cDNA encoding of receptor-associated
      protein of Heymann nephritis (HN) pathogenic epitope into the pGEX. The pGEX-R93
      coding region fragment was confirmed by enzyme cutting and sequencing analysis.
      After the pGEX-R93 was transfected into DH5 alpha, the expression of GST-RAP
      fusion protein was induced by isopropylthio-beta-D-galactoside are the
      overproduced protein consituted 39.4% of the total cellular protein. Western blot
      analysis showed that the antiserum for GST-RAP recognized the 44,000 alpha
      protein band of natural antigen in HN. In addition, immunofluorescence analysis
      showed that the antiserum also distinctively recognized the ciliated membrane
      antigen of the proximal convoluted tubule of the rat kidney.

PMID- 9275654
TI  - [A study on p53 gene mutation, protein expression and relationship with clinico
      pathological status in large cell carcinoma of the lung].
AB  - Immunohistochemistry and in situ hybridization techniques were used to
      investigate the correlation between p53 gene mutation and the clinico
      pathological status as well as prognosis of large cell carcinoma of the lung. p53
      expression was found in 40% of the cases by immunohistochemistry and p53 gene
      mutation was found in 53.3% by in situ hybridization. The concordance ratio was
      73.3% between gene mutation and protein expression. No statistically significant
      correlation was found between p53 gene mutation, its protein expression and sex,
      age, smoking, histological type, tumor size or lymph node involvement. A
      significant correlation was found between p53 gene mutation (or its protein
      expression) and mitotic index. The result of in situ hybridization demonstrated
      that there was a statistically significant correlation between p53 gene mutation
      and a poor prognosis. It was found that p53 gene mutation was associated with
      fast growth of the tumor. Therefore p53 gene mutation is probably an indicator of
      poor prognosis for large cell carcinoma of the lung.

PMID- 9275655
TI  - [Loss of alveolar attachments in smoker's lungs and its relation to small airway
      abnormalities].
AB  - The alveolar attachments and small airway abnormalities in the lungs of smokers
      were measured by computerized imaging to study the relationship between loss of
      alveolar attachments and small airway abnormalities, the smoker's lungs were
      divided into three groups: no emphysema (NE), centrilobular emphysema (CLE) and
      panlobular emphysema (PLE). The distance between normal alveolar attachments
      (Distance) and percent abnormal alveolar attachments (% Abnormal) in CLE were
      significantly higher than in NE (P < 0.05 and P < 0.01), and no significant
      difference in the number of normal alveolar attachments in the 3 groups. The
      small airway wall area (WA) and deformity index (DI) in CLE differed
      significantly from MA and DI in NE (P < 0.05 for all). There were no differences
      between PLE and NE in these indices. Distance and % Abnormal correlated
      significantly with WA and DI, but the correlations were shown only in CLE. We
      concluded that alveolar attachment destruction in smoker's lungs was closely
      associated with small airway abnormalities, which indicated the different
      patterns of emphysema, CLE and PLE, probably have different pathogenesis
      respectively.

PMID- 9275656
TI  - [Effects of oxidized low density lipoprotein and very low density lipoprotein on
      the expression of MCP-1 by monocytes].
AB  - Monocyte chemoattractant protein-1 (MCP-1) is a potent chemotatic factor for
      monocytes. This study aimed at examination of the effects of oxidized low density
      lipoprotein (OX-LDL) and oxidized very low density lipoprotein (OX-VLDL) on the
      expression of MCP-1 mRNA and protein by monocytes. The guanidinium isothiocyanate
      method was used to extract total RNA from monocytes which were exposed to LDL, OX
      LDL, VLDL and OX-VLDL for 24 hours respectively and the monocyte derived
      conditioned media collected. MCP-1 mRNA expression in monocytes was examined by
      slot blot and Northern blot analysis using a gamma 32P-end-labelled 35 mer
      oligonucleotide probe of MCP-1. Meanwhile, MCP-1 protein in the conditioned media
      was examined by use of sandwich ELISA. It was found that monocytes from human
      peripheral blood can express MCP-1 mRNA and protein after 24 hours incubation at
      37 degrees C and the expression of MCP-1 mRNA and protein was markedly increased
      by a 24 hour exposure to OX-LDL and OX-VLDL, whereas the expression of MCP-1 mRNA
      and protein was only sightly increased when exposed to LDL and VLDL. It is
      concluded that monocytes can express MCP-1 that induce additional monocyte
      migration into the subendothelial space, and that OX-LDL and OX-VLDL enhance this
      function by inducing stronger MCP-1 expression in monocytes.

PMID- 9275657
TI  - [Distribution and quantification of oxidative low density lipoprotein in the
      development of atherosclerotic lesions of human aorta].
AB  - A total of 35 human aorta specimens obtained within 12 hours postmortem were
      collected. The distribution pattern and quantity of LDL and ox-LDL in
      atherosclerotic lesions of varying severity and the relationship with aorta cells
      were studied by immunohistochemical techniques and computorized image processing.
      The results showed that the staining pattern with anti-ox-LDL and antibodies to
      apoB was similar; in fatty steaks, the staining for ox-LDL was predominantly cell
      associated in macrophages derived foam cells, in the late lesions, its pattern
      shifted to smooth muscle cells and extra-cellular matrix staining, there was also
      more apoB in fibrofatty plaques and atheromatous plaques than in fatty streaks,
      but no significant difference was found between the two stages of plaques. The
      quantity of Cu(2+)-ox-LDL significantly increased with the development of AS.
      There was more LDL than ox-LDL in fatty streaks, but in the late plaques, there
      was significantly more ox-LDL than LDL.

PMID- 9275658
TI  - [A study on characterization and tumorigenesis of an interleukin 2 gene
      transduced human breast carcinoma cell line].
AB  - Since interleukin 2 (IL-2) can stimulat host immune response, the cDNA encoding
      human IL-2 (hIL-2), mediated by retroviral vector, was transferred into human
      breast carcinoma cell line "MDA-MB-435". The characterization and tumorigenesis
      of hIL-2 gene transduced cells were studied. The results showed that provirus
      genome had been inserted to the genome of transduced cells demonstrated by
      Southern hybridization. One million transduced cells secreted up to 15ng hIL-2 in
      24 hours with ELISA method specific to hIL-2. The mRNA expression of hIL-2 was
      identified by RT-PCR. The hIL-2 gene modified cells lost their tumorigenesis and
      the tumorigenesis by mixed injection with their parent tumor cells was inhibited
      in nude mouse. These data suggest that hIL-2 gene transduced tumor cells may
      represent a potential vaccine in the management of cancer patients.

PMID- 9275660
TI  - [The inhibitory effects of Radix Astragali on hypoxic pulmonary hypertension of
      rats].
AB  - The inhibitory effects of Radix Astragali (RA) on hypoxic structural remodeling
      of intra-acinar pulmonary arteries (IAPA) and pulmonary hypertension (PHT) were
      studied in rats, which were fed in hypoxic environment under normal atmospheric
      pressure (10% O2 10 hours/day). 60 rats were divided into 3 groups; hypoxia
      group, hypoxia+RA group and control group. On the 15th and 30th day of hypoxia,
      right ventricular systolic pressure (RVSP) and right ventricle hypertrophy index
      (RVHI) were measured and pulmonary vessel changes were studies under light and
      electronic microscopes and morphometric analysis. Compared with the hypoxia+RA
      group, RA could prevent IAPA wall cell damage and dilate the constricted IPIA
      induced by hypoxia. RA could also inhibit hypertrophic changes in the tunica
      media and proliferation of adventitial cells of the IAPA and muscularization of
      non-muscular arteries. Therefore, preserving the IAPA wall cells and dilating
      IAPA by RA may play an important role in inhibiting structural remodeling of IAPA
      and pulmonary hypertension.

PMID- 9275659
TI  - [Studies on MDM2 oncogene expression and its effect on pancreatic carcinoma
      cells].
AB  - In order to study the interrelation and interaction between MDM2 oncogene and
      wild type p53 in human pancreatic cancer, we studied the expression and
      amplification of MDM2 oncogene and its antagonistic effect on wild type p53 by
      use of gene recombination, gene transduction and molecular hybridization
      techniques. The results showed that MDM2 oncogene could be detected in all 5
      pancreatic cell lines, but MDM2 mRNA expression varied in the different cell
      lines. The recombinant vector pCMV-MDM2 was transduced into PC-2/s-wtp53 cell
      line (a transformed PC-2 pancreatic carcinoma cell line containing wild type p53
      gene). The resultant cell line, PC-2/s-wtp53/pCMV-MDM2 showed rapid cell growth,
      a rate similar to that of the parent cell line PC-2. Our results verify the fact
      that MDM2 gene can abrogate the cell growth arrest mediated by wild type p53 and
      the antagonistic function of wild type p53.

PMID- 9275661
TI  - [A pathologic study of delayed myocardial reperfusion injury].
AB  - This study was designed to investigate whether a new irreversible injury to the
      myocardium can occur 6 hours after reperfusion following ischemia. Conscious
      rabbits were subjected to myocardial ischemia for 30 minutes, followed by
      reperfusion. Horseradish peroxidase (HPR) tracing with TTC staining and
      histological quantification were used to study the histopathological changes in
      myocardial tissues. Necrotic myocardium at 6 hours after reperfusion gave
      positive HRP results and viable myocardium at 24 hours after reperfusion gave
      positive TTC results. Some myocardial tissue between the above two regions were
      found to be HRP negative as well as TTC negative, indicating that myocardial
      tissue death occurred between 6 to 24 hours after reperfusion. The myocardial
      infarct size at 24, 48, and 72 hours after reperfusion were 7.0%, 5.1% and 3.2%
      larger than that 6, 24 and 48 hours respectively. Therefore, new irreversible
      myocardial injury in the rabbit can still occur after 6 hours of reperfusion
      following myocardial ischemia for 30 minutes and cumulative myocardial injury
      from 6 to 72 hours after reperfusion can result in a marked extension of the size
      of myocardial infarct.

PMID- 9275662
TI  - [A clinical and pathological study of gliosarcoma].
AB  - In order to study the clinicopathological features, histogenesis and prognosis,
      12 cases of gliosarcoma were reported representing 0.4% of a series of 2743
      patients undergoing biopsy for CNS tumors. All the tumors originated from the
      cerebral hemispheres with a predilection for the temporal lobes. Half of the
      cases show more firm consistency and are rather well demarcated from brain
      tissue. Clinically, they are sometimes mistaken for meningiomas. Of the 10
      patients with follow-up, 9 have died. The mean survival period after operation
      was 8 months, 1 cases is still alive and well for 3.2 years. There were some
      cases in which the origin of spindle cell populations could not be determined by
      H & E staining. Glioblastoma and malignant fibrous histiocytoma (MFH) element of
      the tumor was confirmed by electron microscopical examination and
      immunohistochemical stains for GFAP, Mac 387, VIM, FV III RA, etc. Osteosarcoma
      component in the tumor was detected in one case. It was accepted that MFH arose
      from the primitive uncommited mesenchyme.

PMID- 9275663
TI  - [Inhibitory effect of antisense LIF oligonucleotide on the outgrowth of human
      medulloblastoma cells].
AB  - In order to analyse the functional importance of leukemia inhibitory factor (LIF)
      in the prolliferation of human medulloblastoma cells, antisense LIF
      oligonucleotides were used to block LIF gene expression in established
      medulloblastoma cell line Med-3. The effects of this measure on Med-3 cells were
      then investigated by using different approaches. The results revealed that LIF
      expression in the cells treated by antisense LIF reduced below the threshold
      being detectable with RT-CPR and anti-LIF immunocytochemistry also showed a
      negative lebelling. Meanwhile, proliferation rate of antisense treated cells
      decreased distinctively. In contrast, the LIF gene expression as well as
      proliferation of Med-3 cells treated by sense oligonucleotides remained similar
      as that of the normally cultured cells. The data suggest a LIF oriented
      gene/immune trial for the therapy of medulloblastomas and other LIF growth
      associated tumors of humans.

PMID- 9275664
TI  - [A pathological analysis of 180 cases of vascular malformation of brain].
AB  - 180 cases of vascular malformation in brain (BVM) including 156 cases of brain
      biopsy and 24 autopsy cases were examined with routine pathological methods. The
      attempt of this study is to realize the pathological change and incidnce of each
      type and to find out the main cause of hemorrhage in BVM. According the
      morphological characteristics, 180 cases of BVM were classified into five types.
      They are: arteriovenous type 159 cases, venous type 3 cases, cavernous type 6
      cases, capillary telangiectasis 1 case, and mixed type 11 cases. Hemorrhage was
      the most common clinical manifestation and main cause of death in BVM. The
      mechanism of hemorrhage may be due to either hemodynamic disturbance in local
      area or changes of the blood vessel wall. Besides these, there are five cases of
      BVM accompanied with brain tumor. They may be two independent diseases occurred
      in the same person. No relationship was found between the occurrence of these 2
      entities.

PMID- 9275665
TI  - [Morphological effects of ammonia on cultured fetal rat neurons].
AB  - The effects of ammonia on cultured fetal rat neurons and the possible relation
      between morphologic changes of neurons and the pathogenesis of hepatic
      encephalopathy were studied on dissociated fetal rat neuronal cultures, using
      light microscopy, transmission electron microscopy and immunohistochemistry
      methods. The neurons exhibited cellular swelling, chromatolysis, vacuolization
      and granulation, followed by segmental enlargement and fragmentation of cellular
      processes, detachment of neurons with pyknotic nuclei. Electron microscopic
      examination displayed dilation of mitochondria and endoplasmic reticulum,
      degranulation of rough endoplasmic reticulum, accumulation of dense bodies
      together with swelling of the process with loss of neurofilaments. The expression
      of neurofilament and synaptophysin became weak and even negative. The data
      therefore suggests that ammonia may exert a toxic effect on cultured neurons,
      disturbing their normal function and facilitating the development of hepatic
      encephalopathy.

PMID- 9275666
TI  - [A clinicopathological and immunohistochemical study of 34 cases of chordoma].
AB  - In order to investigate the clinicopathological and immunohistochemical features
      of chordomas, 34 chordomas, with 5 chondrosarcomas for comparison, were studied
      by clinicopathological and immunohistochemical methods. RESULTS: Based on the
      presence or absence of cartilaginous areas, chordomas are classified into two
      subtypes: chondroid chordoma (14 cases) and classic chordoma (20 cases).
      Chondroid chordoma occurred in a younger age group (mean age 40.9 years) than
      classic chordoma (mean age 51.1 years). 7/14 (50%) of chondroid chordomas
      occurred in the sacrococcygeal region, 4/ 14 (28.6%) occurred in the spheno
      occipital region. Immunohistochemical staining showed that all chordomas were
      positive for cytokeratin, and 16 (47.1%) chordomas were also positive for EMA. In
      contrast, 5 chondrosarcomas were immunonegative for both cytokeratin and EMA.
      Vimentin and S-100 protein were positive in the majority of chordomas (29 & 24
      respectively) and in the 5 chondrosarcomas. The present study confirms the dual
      features of chordoma-epithelial and mesenchymal, and also the utility of
      immunohistochemical staining in the differential diagnosis of chordoma and
      chondrosarcoma. The pathologic diagnosis of chondroid chordoma and other issues
      were also discussed in the study.

PMID- 9275667
TI  - [Expression of tissue-type plasminogen activator (t-PA) in smooth muscle cells of
      injured iliac arteries in rabbits].
AB  - To investigate the mechanism of atherogenesis and development of restenosis
      following angioplasty, the expression of t-PA in SMC at different intervals after
      the arterial injury was measured by morphological analysis, plasmin generation
      assay and in situ hybridization. t-PA activity of the iliac arteries was noticed
      to be significantly increased on the 4th day after injury, signalling the
      commencement of SMC migration from the media to intima, t-PA activity then
      decreased to approximately the normal level on the 7th day. Results from in situ
      hybridization also showed that the expression of t-PA mRNA in the intima and
      media increased significantly on the 4th day after the arterial injury, by the
      7th day, t-PA mRNA was detected only in SMC located adjacent to the internal
      elastic lamina. These results suggest that t-PA might play an important role in
      SMC proliferation and migration following arterial injury.

PMID- 9275668
TI  - [Expression and significance of bcl-2 oncogene protein in follicular lymphoma and
      lymphoid follicular hyperplasia].
AB  - In order to distinguish follicular lymphoma (FL) from follicular hyperplasia
      (FH), immunohistochemical staining method was used to detect the expression of
      bcl-2 oncogene protein in 22 cases of FL and 14 cases of FH. The results showed
      that bcl-2 was positive in 19 and negative in 3 of the 22 FLs, but negative in 12
      and weakly positive in 2 of the FHs. These findings suggest that bcl-2 can play
      an important role in the differential diagnosis of FL and FH.

PMID- 9275669
TI  - [Detection of bcl-2/JH fusion gene in patients with non-Hodgkin's lymphoma by
      semi-nested polymerase chain reaction].
AB  - To study the incidence and clinical significance of bcl-2/JH fusion in 45 Chinese
      patients with non-Hodgkin's lymphoma, semi-nested polymerase chain reaction (PCR)
      was used to detect the fusion gene of non-Hodgkin's lymphoma. A total of 12
      patients gave positive results, they include 9 of the 15 patients with follicular
      lymphoma and 3 of the 30 patients with diffuse B-cell lymphoma. The results were
      negative in 5 patients with reactive hyperplasia. The breakpoint was located
      within the major breakpoint region in 11 of the 12 patients, and the remaining
      patient had bcl-2 translocation in the minor cluster region. The results of the
      study show that bcl-2/JH fusion gene in non-Hodgkin's lymphomas is an important
      molecular biological marker and has a significant role in differentiating benign
      or malignant hyperplasia, determination of clonality, predicting prognosis and in
      the discovery of minor residual disease.

PMID- 9275670
TI  - [The significance of detecting Epstein-Barr virus DNA and latent membrane protein
      I in Hodgkin's disease from a high incidence area of nasopharyngeal carcinoma].
AB  - To study the EBV DNA and expression of latent membrane protein I (LMP1) in
      patients with Hodgkin's disease from high incidence area of nasopharyngeal
      carcinoma, hot starting PCR and microwave treatment of LSAB immunohistochemistry
      methods were used to detect EBV DNA and LMP1 from biopsy specimens from 40 cases
      of Hodgkin's disease (HD) and 20 cases having benign lymph node lesions, randomly
      selected from a high incidence area of nasopharyngeal carcinoma. EBV DNA was
      detected in 65.0% of the HD cases and 50.0% of the benign lymph node cases, the
      difference was not of statistical significance. LMP1 of EBV was detected in 52.5%
      of HD cases and its expression was restricted to tumor cells. In addition, the
      detection rates of LMP1 and DNA of EBV in patients under 20 years of age (84.6%
      and 76.9% respectively) was much higher than that in patients over 20 years of
      age (56.0% and 40.0% respectively) P < 0.05. The results suggest that there was
      latent EBV infection in at least half of HD patients, which may have a role in
      the genesis and development of HD, and HD occurring in youth was more closely
      correlated with EBV latent infection and LMP1 expression.

PMID- 9275671
TI  - [Study of heterogeneity in DNA ploidy and its clinical-pathological significance
      in esophageal squamous cell carcinoma].
AB  - In order to investigate the intratumoral DNA ploid heterogeneity in esophageal
      squamous cell carcinoma and its significance, nuclear DNA ploidy of 80 cases of
      squamous cell carcinoma of the esophagus were determined for multiple samples
      obtained from the same tumor, using a flow cytometry (FCM) technique. The results
      showed that: (1) DNA indeces ranged from 7.7-1.74, and the incidence of DNA
      aneuploidy was 88.8% (71/80) in this series; (2) of 80 cases, (47.5% 38 cases)
      showed intratumoral heterogeneity in DNA ploidy (3) the heterogeneity in DNA
      ploidy was related to the extent of wall penetration by tumor, the incidnce of
      lymph node metastasis and patient's prognosis, not to histological grades and
      size of tumor. The results from this study indicated that DNA ploidy
      heterogeneity may be a exact indicator in reflecting the biological
      characteristics of tumor and patient's prognosis than DNA aneuploidy from single
      site sampling.

PMID- 9275672
TI  - [A study of HIA-DR antigen expression in nasopharyngeal carcinoma and its
      relation with clinical pathology and prognosis].
AB  - In order to clarify the relationship between HLA-DR antigen expression of
      nasopharyngeal carcinoma (NPC) and the clinicopathology and prognosis of NPC,
      immunohistochemical studies on HLA-DR antigen expression in 77 NPC cases were
      performed. The results showed that the positive rate of HLA-DR was 44.2% in this
      series. Non-neoplastic epithelium did not express this antigen. A close
      association was found between expression of HLA-DR antigen and the clinical
      staging of NPC. The positive rate of HLA-DR gradually decreased with tumor
      progression, showing a remarkable difference among tumors in different clinical
      stages (P < 0.05). Analysis of patient survival demonstrated that the prognosis
      of NPC patients with HLA-DR expression was significantly better than those
      without (P < 0.01). The above results give support to the possibility of
      immunomodulation of tumors.

PMID- 9275673
TI  - [The expression of bcl-2, P53 and c-erbB-2 onco-proteins in breast cancer and
      their clinicopathological significance].
AB  - In order to study the interrelation between bcl-2, P53 and c-erbB-2 protein,
      their expression in 145 breast carcinomas were observed by immunohistochemical
      LSAB method. 19 cases were negative, 12 were positive for the three oncoproteins.
      19 cases were positive for c-erbB-2 only. 20 positive for P53 only and 20
      positive for bcl-2 only. 26 cases were positive for both P53 and c-erbB-2, 17 for
      both c-erbB-2 and bcl-2, 12 for both P53 and bcl-2. Strong inverse correlation
      was found between the expression of P53 and bcl-2 (P < 0.001). The P53 expression
      or the expression of both P53 and c-erbB-2 correlated with low histological
      grade, while the bcl-2 expression correlated with high histological grade (P <
      0.05). The necrosis in tumors with only bcl-2 expression was less than those with
      c-erbB-2 or both c-erbB-2 and P53 expression (P < 0.02). Mitosis count was lower
      in tumors with only bcl-2 expression than those with expression of both c-erbB-2
      and P53 (P < 0.05). The expression of c-erbB-2 and P53 proteins are associated
      with poor prognosis (P < 0.02, P < 0.05) but not affected by bcl-2. The results
      suggest that bcl-2, P53 and c-erbB-2 are involved in tumorigenesis and
      development of breast carcinoma with different biological effects.

PMID- 9275674
TI  - [Current status and trends of nuclear DNA assessment and ploidy analysis of
      neoplasms].

PMID- 9275675
TI  - [Advances in the research on multidrug resistance genes].

PMID- 9275676
TI  - [Rapid genotyping for HLA-DR by PCR-amplification with sequence-specific primers
      and clinical practice].
AB  - Genotyping for HLA-DR alleles by polymerase chain reaction with sequence-specific
      primers (PCR-SSP) was first typed in 112 individuals of donor-recipients of
      cadaveric transplantation and 9 cell lines DNA. Twenty separate PCR reactions
      were performed per sample. The amplification was accomplished by 34 cycles
      consisting of denaturation at 94 degrees C for 30 sec, annealing at 60 degrees C
      for 50 sec and extension at 72 degrees C for 40 sec. HLA-DR alleles could be
      accurately distinguished. The overall time of genotyping was only 5 hours. The
      specificity of matching was determined against a panel of standard DNA, analysis
      with restriction endonucleases, and Southern hybridization using DIG
      oligonucleotide 3'- end labeling probes. The specificity and reproducibility were
      100%. No false positive or false negative typing results were obtained. These
      showed genotyping by PCR-SSP was a rapid and accurate matching technique, suited
      for clinical practice.

PMID- 9275678
TI  - [Labeling of antihuman bladder carcinoma monoclonal antibody with a technetium
      99m and radioimmunoimaging of human bladder carcinoma xenograft in nude mice].
AB  - Anti-human bladder carcinoma cell line BIU-87 monoclonal antibody-BDI-1 was
      labeled with 99mTc by direct mercaptoethanol reducing method. Quality control
      tests showed that the labeling yield was 69.9%; the radiochemical purity was
      higher than 90%; the immunoreactive fraction of 99mTc-BDI-1 was 81% and the
      association constant was 1.22 x 10(-9) M-1. The radioimmunoimaging of human
      bladder carcinoma xenograft in nude mice and the biodistribution of 99mTc-BDI-1
      were studied. After having been scintigraphed at three time intervals (at 4, 16
      and 22 hour), the animals were sacrificed for biodistribution of 99mTc-BDI-1.
      Tumor can be seen clearly at 22 hour after intravenous injection of 99mTc-BDI-1;
      %ID/g (percentage of the injected dose per gram of tissue) of tumor was 20.70,
      the average T/NT was 10.52, the minimum T/NT was 2.90 (tumor/kidney) and the
      maximum T/NT was 20.70 (tumor/small intestine or muscule). The results above
      indicated that 99mTc-BDI-1 can be used for radioimmunodetection of human bladder
      carcinoma in vivo and BDI-1 may be suitable as a targeting device in patients.

PMID- 9275677
TI  - [Inhibitory effects of malignant phenotype of human bladder cancer cell line by c
      Ha-ras, c-myc antisense oligodeoxynucleotide].
AB  - The effects of two antisense oligodeoxynucleotide on expression of c-Ha-ras, c
      myc proto-oncogene and the growth of human bladder cancer cell line were
      observed. Synthetic 15-mer directed at the region of the translational initiation
      site of c-Ha-ras, c-myc proto-oncogene (ASO-r, ASO-m) greatly inhibited the
      proliferation and DNA synthesis of T24 cell line, inhibited the expression of
      rasp21, mycp62 protein. The power of tumorigenesis of cell line treated with ASO
      was decreased. The results implicate the potential value in bladder cancer gene
      therapy.

PMID- 9275679
TI  - [Amplification, cloning and sequence analysis of the variable region genes of
      monoclonal antibody against human bladder carcinoma].
AB  - We have designed two sets of oligonucleotide primers to amplify the
      immunoglobulin heavy- and light-chain variable region genes from genomic DNA by
      the polymerase chain reaction, PCR. The genomic DNA was extracted from hybridoma
      BDI-1 cell, which secrets a monoclonal antibody against human bladder carcinoma.
      The primers contain special restriction sites that allow the variable region
      genes to be easy to cloning for sequencing and expression. The PCR products were
      ligated to plasmid PUC19. The recombinants were sequenced with Sanger's method.
      It was proved that a full-length VH and V kappa genes was 366 and 324 base pairs
      respectively. Comparaing with other published sequences, the VH gene was a member
      of mouse heavy-chain VH subgroup II and originated from rearrangement of VH,
      Dsp2.2 and JH4; the V kappa gene was V kappa subgroup IV and from V kappa and J
      kappa 4. It was suggested that obtained VH and V kappa genes were potentially
      functional genes of the monoclonal antibody against human bladder carcinoma.

PMID- 9275680
TI  - [Level and significance of the soluble interleukin-2 receptor expression in serum
      of patients with bladder cancer].
AB  - The results of a dynamic study of the soluble interleukin-2 receptor (SIL-2R)
      expression, interleukin-2 (IL-2) production and natural killer cell factor (NKCF)
      activity before and after operation in 24 bladder carcinoma patients were
      reported. The SIL-2R expression level in the patients was significantly higher,
      the IL-2 production and NKCF activity were remarkably lower than those of
      controls. Furthermore, the higher the stage of the tumor, the higher the level of
      the SIL-2R. There was a period of immune suppression after operation. The results
      suggest that the changes of the SIL-2R expression level, IL-2 production and NKCF
      activity are closely related to the prognosis of patients with bladder carcinoma.

PMID- 9275681
TI  - [Role of PCR and dot bolt hybridization in the detection of human papillomavirus
      of the penile cancer].
AB  - Human papillomavirus (HPV), a oncogenicpotential, may be carcinogenic effectors
      in variety of genital tract malignancies. We examined the association of human
      papillomavirus type 16 and 18 in 28 penile cancers by the highly sensitive
      polymerase chain reaction and dot bolt hybridization. Human papillomavirus type
      16 was found in 14 of 28 penile cancers (50%), whereas type 18 was identified in
      3 of 28 penile cancers (10.6%). Our results suggest humanpapillomavirus type 16
      may play a role in the development of this tumor and associate with smoking and
      ages of patients.

PMID- 9275682
TI  - [IL-6 gene expression in human tumor cell lines].
AB  - Using Northern blot techniques and IL-6-dependent cell line proliferating
      response method, the IL-6 gene expression in 8 sorts of human tumor cell lines
      and the IL-6 biologic activity in 5 sorts of medium were investigated. The
      results revealed that IL-6mRNA was positively expressed in 7 sorts of these cell
      lines and there were differential IL-6 biologic activity in 5 sorts of assayed
      medium. These results may providea basis for further research.

PMID- 9275683
TI  - [Left single lung transplantation in treatment of idiopathic pulmonary fibrosis:
      a case report].
AB  - A single left lung transplantation was performed on a 48-year-old male with end
      stage idiopathic pulmonary fibrosis in February 1995. The surgical technic used
      was similar to that mentioned in the literature. The donor lung was perfused by
      cold Euro-Collins solution with a cold ischemic time of 190 minutes.
      Cardiopulmonary bypass was not used. The patient weaned from ventilator on the
      next day of operation (22 hours). Immunosuppression included cyclosporine,
      azathioprine and corticosteroid using until now and antithymocytic globuline for
      five days. Three episodes of acute rejection occurred within three months after
      operation, and all cured by bolus methyl-prednisolone given intravenously. The
      patient remains well nine months after operation with significant improvement of
      lung function and enjoies normal life.

PMID- 9275684
TI  - [Treatment and prognosis of soft tissue sarcoma].
AB  - The treatment and prognosis of 121 patients with primary and locally recurrent
      soft tissue sarcomas of the extremities and trunk were analyzed. The most common
      histologic type was malignant fibrous histocytoma (32 patients, 26.4%). Ninety
      three patients had high grade sarcomas (76.9%) and 28 had low grade sarcomas
      (23.1%). Adjuvant radiotherapy and chemotherapy were applied to 37 and 41
      patients respectively. In 28 patients who had local recurrence after surgery, the
      5-year local control rate was 72.3%. The overall 5-year survival rate was 59.9%
      for all patients, and 59.1% for 96 patients with locally recurrent lesions. The
      independent risk factors affecting the overall survival included high grade,
      tumor of upper extremity, perioperative blood transfusion, and tumor size of > or
      = 10 cm. We conclude that (1) wide excision is the most accepted operative
      procedure for treatment of soft tissue sarcoma of the extremity and trunk unless
      the lesions are locally advanced (In the advanced cases amputation should be
      performed); (2) in patients with local recurrence only, there is an almost same
      rate of long-term salvage as that in patients with primary tumors; (3) avoiding
      unnecessary perioperative blood transfusion may improve survival; and (4) further
      investigation of more effective regimen of adjuvant radiotherapy and chemotherapy
      needs to be taken.

PMID- 9275685
TI  - [Studies of aetiology and management about iatrogenic injuries of bile duct].
AB  - 74 patients with iatrogenic injuries of bile duct were treated from June 1965 to
      October 1994 in our hospital. Iatragenic extrahepatic bile duct injuries may be
      caused by some errors during cholecystectomy. The operator did not realize that
      cholecystectomy itself is a procedure with inherent and potential risks. The
      operator was careless, rude and arrogant in operating. The operator lacked
      experience and skill, and was unable to deal with difficult situation during
      operation. Also we discussed the management of bile duct injuries, and suggested
      that intraoperative injuries of extrahepatic bile duct should be reconstructed
      immediately including repair of or end to end anastomoses of the injuries of bile
      duct. Cholecystojejunostomy (Roux-en-Y technique) is the best reconstruction
      procedure for patients with the injuries of bile duct after operation or failure
      of repetitional repaired and reconstructive operations of bile duct. Satisfactory
      result could be obtained.

PMID- 9275686
TI  - [Gastric devascularization for acute gastric mucosal lesion and bleeding].
AB  - Thirteen patients with acute gastric mucosal lesion and bleeding were treated
      with gastric devascularization. Of all, 11 apparently stopped bleeding, two
      failed to respond to the procedure, one rebled, and three died. Clinical analysis
      of the patients suggested that low blood pressure, damage of liver function,
      serious infection, acidosis and uremia were precipitating factors of the disease
      and for AGML in portal hypertension, the effect of this procedure was poor.
      Meanwhile, the etiology and pathological mechanism of AGML, the selection of
      operation types for the disease, and the anatomical and physiological bases of
      gastric devascularization were also discussed.

PMID- 9275687
TI  - [Functional motor innervation of brachial plexus roots: an intraoperative
      electrophysiological study].
AB  - The electrophysiological properties of normal brachial plexus and functional
      motor innervation during the operation of contralateral healthy side C7 transfer
      were studied different roots of brachial plexus were stimulated and maximum
      amplitudes were recorded. The results showed functional motor innervation of
      brachial plexus roots are (1)C5 mainly forms the axillary nerve which innervates
      deltoid muscle; (2)C5 constructs most of the musculocutaneous nerve fibers which
      innervate biceps muscle; (3)main component of the radial nerve comes from C7,
      which innervates triceps muscle; (4)Medial nerve mainly comes from C8, which
      innervates flexor digitorum muscle; (5)T1 forms most of the ulnar nerve which
      innervates intrinsic muscle. Based on the relationship between brachial plexus
      roots and their functional distribution, the particular aspects of functional
      innervation of C7 as well as the possibility of utilization of other cervical
      roots were discussed.

PMID- 9275688
TI  - [Regenerating axons selectively reinnervate their target organs after the
      peripheral nerves were tubulated].
AB  - This study investigated target specificity during axonal regeneation of a mixed
      motor and sensory nerve after the canine tibial nerves were tubulated. 10mm gap
      of tibial nerve was connected by silicone tube. Three months later, the second
      operation was performed by spinal dorsal root ganglion (DRG) resection at the
      experimental side. Five months later, histalogical analysis results reveal that
      the regenerating motor nerve fibre of mixed nerve selectively grew into motor
      branches. The mean number of regenerated motor nerve fibers grew into its motor
      branches was 1199, and the number of that into its sensory branch was only 21.
      This result suggests that regenerating motor and sensory axons of mixed nerve can
      across 10-mm silicone chamber and be able to select their distal target organs
      exectly.

PMID- 9275689
TI  - [The injury of liver sinusoidal endothelial cells in a rat's isolated liver
      perfusion (ILP) model for regional chemotherapy].
AB  - To observe the pathological changes of liver sinusoidal endothelial cells, the
      regional perfusion with different dosage of 5-FU was performed by using modified
      rat's model of ILP. The results demonstrated that ILP with over maximum tolerence
      dosage of (MTD) 5-FU resulted in irreversible damage of liver and endothelial
      cells. The endothelial cells were more fragile than liver cells. The changes of
      TXA2 and PGI2 balance play an important role in the process of damage of
      endothelial cells.

PMID- 9275690
TI  - [The relationship between selenium and immunity in large bowel cancer].
AB  - 44 patients with large bowel cancer were randomly divided into two groups,
      therapeutic and control group. The level of serum selenium, T lymphocyte subsets
      consisted of CD3, CD4, CD8, CD4/ CD8, NK and LAK cell activity were measured
      preoperation and postoperation. Simultaneously se content in tumor and normal
      tissue of the large bowel were measured in 35 cases. Serum se level (0.81 +/-
      0.14 umol/L) was lowered in patients with large bowel cancer and increased
      significantly after se supplementation in the therapeutic group (P < 0.01). It
      was significantly different from that of the control group (P < 0.01), CD3, CD4,
      CD4/CD8, NK and LAK cell activity were obviously increased postoperatively in the
      therapeutic group and significantly different from those of the control group.
      The results suggest that supplement of Se can promote cell-mediated immunity in
      humans. In addition, Se can promote cell-mediated immunity in humans. The Se
      level of 22. 13 +/- 1.76 umol/g in tumor was significantly lower than that of
      24.30 +/- 1.96 umol/g in normalmucosa in case of large bowel cancer (P < 0.01).
      This indicates that there may be a close relationship between low se level and
      the carcinogenesis of the colon and rectum.

PMID- 9275691
TI  - [Preoperative intraluminal 5-FU osmosis chemotherapy as an adjuvant to radical
      resection for rectal cancer].
AB  - Patients with rectal cancer of stage dukes B and C were randomized into two
      groups. In osmosis chemotherapy group 86 patients were treated by radical
      resection plus adjuvent preoperative intraluminal 5-FU osmosis chemotherapy at
      the area of tumor. In control group 74 patients were treated by radical resection
      alone. There were high concentration of 5-FU in the cancer, mucosa and lymph node
      around the cancer and mesenterica inferior venae, and the lower in a round venae.
      After the chemotherapy the symptoms were improved without side-effects, the II
      III grade at pathological change was 83%, the cancer regression more than 50 was
      38%. Compared the two groups osmosis chemotherapy raised 14% at radical resection
      and reduced 22%, 11%, 22% at local recurrence and metastasis of lymph nodes and
      liver. The 3-, 5-year survival rates (81.1%, 69.6%) were higher than 19.2%, 26.7%
      in the control group.

PMID- 9275692
TI  - [Molecular weight determination and protein analysis of GCF-5 antigens of giant
      cell tumor of bone].
AB  - In order to understand the tumor antigen(s) of giant cell tumor of bone (GCT),
      monoclonal antibody GCF-5 developed in this laboratory was employed. GCF-5
      reacted specifically against the tumor cell associated antigens of GCT. The
      membrane proteins of tumor cell were extracted by high concentration of SDS,
      followed by a series of treatment processes, including SDS-PAGE, western blotting
      and some staining methods, such as Periodic-Schiff for glycoprotein and oil red O
      for lipoprotein. The molecular weight and chemical characteristics of GCF-5
      antigens were analysed. The preliminary results indicated that the main GCF-5
      antigens were two glycoproteinis containing few saccharide chains, one of which
      was 13.5KD and the other 17.4KD.

PMID- 9275693
TI  - [Dorsal root ganglia of the lumbosacral region and their clinical significances].

PMID- 9275694
TI  - Factors accounting for different responses of pulmonary and cerebral vessels to
      hypoxia.
AB  - The roles of sympathicus, sensory neuropeptides (SNP), cyclooxygenase metabolites
      (COX-M), lipoxygenase metabolites (LOX-M), endothelium derived relaxing factor
      (EDRF), reactive oxygen (ROS) and potassium channels (PC) in the hypoxic
      pulmonary vasoconstriction (HPV) and hypoxic cerebral vasodilation (HCVD) were
      investigated in intact rats, rabbits and dogs. The results showed that during
      hypoxia, the excitation of sympathicus caused a constriction of both pulmonary
      and cerebral vessels, while SNP, EDRF and the opening of voltage sensitive PC
      caused the dilation of both of them; LOX-M mediated HPV and HCVD, COX-M might
      serve as their modulators; the blockade of ATP sensitive PC induced by hypoxia
      mediated HPV, but had no effect on HCVD; the reduction of O2-. in the lung might
      potentiate HPV, however, O2-. remained unchanged in brain during hypoxia. It is
      suggested that the alterations of LOX-M, ROS and the ATP sensitive PC are the
      factors accounting for the difference in the response of pulmonary and cerebral
      vessels to hypoxia.

PMID- 9275695
TI  - Construction of expressing plasmids of recombinant FN polypeptides with
      bifunctional-domain and the characterization of the products expressed in E.
      coli.
AB  - Two expressing plasmids have been constructed and used to express two
      bifunctional-domain recombinant polypeptides of human fibronectin (FN) in E.
      coli. One was CH50 (Pro1239-Ser1515 of FN linked with Ala1690-Thr1960 of FN
      through Met) and the other was CH56 (Pro1239-Thr1960 of FN). Both of two
      polypeptides were capable of binding heparin and were purified by heparin-agarose
      affinity chromatography. The purified products were capable of binding cells. The
      production of CH50 and CH56 polypeptides provided a fundamental basis for further
      study of the anti-metastatic function of recombinant fibronectin polypeptides.

PMID- 9275696
TI  - Correlated flow cytometric analysis of H-ras p21 and DNA ploidy in acute
      myelogenous leukemia.
AB  - The flow cytometric immunoassay was used to study the correlation between the H
      ras oncogene product p21 and the DNA ploidy in 30 de novo cases of acute
      myelogenous leukemia (AML). The results showed that 17 cases were negative for
      p21 expression and 13 positive for p21. The patients with positive p21 had higher
      percentage of bone marrow and peripheral blasts and lower peripheral leukocyte
      count. The expression of p21 had no influence on the therapeutic effect. Before
      treatment, DNA diploidy occurred in 18 cases including 13 p21 negative ones, and
      DNA aneuploidy was revealed in 12 cases including 8 p21 positive ones. Patients
      with positive p21 or having aneuploidy in complete remission were at risk for
      early relapse. Our results suggest that p21 may be involved in the process of
      leukemogenesis and progression in AML.

PMID- 9275698
TI  - Differentiation of osteoblast in vitro is regulated by progesterone.
AB  - The regulation of cellular differentiation by progesterone in fetal rat calvarial
      osteoblasts was investigated. Our results showed that cells cultured in the
      presence of progesterone had a 7% increase in the alkaline phosphatase activity
      when compared to untreated cells. The concentration of osteocalcin in the
      conditioned medium from progesterone treated osteoblasts was 28% higher than that
      of untreated controls. In addition, administration of progesterone significantly
      enhanced the number and area of bone nodules. In conclusion, progesterone
      stimulates the differentiation of fetal rat calvarial osteoblastic cells in
      vitro.

PMID- 9275697
TI  - Partial purification of smooth muscle cell derived growth factor.
AB  - The serum free medium conditioned by cultured rabbit aortic smooth muscle cells
      was partially purified using ultrafiltration and heparin affinity chromatography.
      Incorporation of [3H]-thymidine (3H-TdR) into cell DNA was used to measure the
      mitogenic activity of the fractions from chromatography for NIH 3T3 fibroblasts.
      The molecular weight and the iso-electric point of these fractions were
      determined by NaDodSO4-polyacrylamide gel electrophoresis (SDS-PAGE) and iso
      electric focusing, respectively. The results showed that the protein eluted in
      1.0-1.6 mol/L NaCl from the heparin-Sepharose was mitogenic for 3T3 cells, and
      this protein had a molecular weight of 22.8-26.7 ku and an iso-electric point of
      about 4.6. The fact that the above-mentioned biochemical properties differed from
      that of PDGF, IGF and FGF suggests that this mitogenic protein may be a separate
      growth factor.

PMID- 9275699
TI  - Experimental study on the early efficacy of excimer laser with adjunctive balloon
      angioplasty in dog's femoral artery.
AB  - The effect of domestically-manufactured excimer laser with adjunctive balloon
      angioplasty in achieving revascularization and reduction of residual stenosis was
      assessed. 20 femoral arteries with thrombosis and occlusion from 12 dogs were
      subject to angiography. At first excimer laser angioplasty was done followed by
      balloon angioplasty. The diameter and residual stenosis of revascularized vessel
      were measured. The result showed that 17 out of 20 vessels (85%) were
      revascularized. The diameter of revascularized vessel by excimer laser were 1.22
      +/- 0.14 mm, while residual stenoses were 54% +/- 5%. After adjunctive balloon
      angioplasty the diameter and residual stenoses were 2.04 +/- 0.16 mm and 20% +/-
      7% respectively (P < 0.05 and P < 0.01). Complication in form of vasoperforation
      occurred in 3/20 vessels (15%). It is concluded that China- manufactured excimer
      laser angioplasty is effective when used for revascularization. While the
      reduction of narrowing and residual stenoses was enhanced after adjunction of
      balloon angioplasty. This method can be employed in treating peripheral occlusive
      disease effectively and safely.

PMID- 9275700
TI  - The value of perioperative echocardiography in percutaneous balloon mitral
      valvuloplasty.
AB  - In order to investigate the value of perioperative echocardiography in
      percutaneous balloon mitral valvuloplasty (PBMV), two-dimensional
      echocardiography (2-DE), Doppler echocardiography and color Doppler flow imaging
      (CDFI) were employed prior to PBMV in 52 patients and during or after PBMV in 15
      patients. The results showed that TTE and TEE were helpful in the selection of
      candidates for 2-DE transseptal and balloon dilation procedures. Continuous
      monitoring of 2-DE, Doppler echocardiography and CDFI during PBMV could make this
      procedure safer and more effective, reduce X-ray exposure and avoid
      complications. Echocardiography was useful in fluoroscopy and could be used for
      evaluation of the effects of operation.

PMID- 9275701
TI  - Surgical treatment of ascending aortic dissecting aneurysm--clinical application
      of modified Cabrol's operation.
AB  - This paper reported 3 cases of ascending aortic dissecting aneurysm treated by
      modified Cabrol's operation. An 8 mm Gore-Tex connected with coronary arteries
      was employed to prevent high tension, intimal tearing and bleeding of
      anastomosis. Unremoved aneurysmal wall used as a sac for enclosing conduit graft
      could minimize the bleeding and oozing so that leaked blood can be drained to
      right atrium via a bypass.

PMID- 9275702
TI  - The observation of complement activation and polymorphonuclear neutrocytopenia
      during cardiopulmonary bypass.
AB  - By determining the plasma levels of C2, C4, factor B and polymorphonuclear
      neutrophils (PMNs) of the patients who received CPB, the path of complement
      activation and changes of PMNs were studied. The results suggest that complement
      system was activated through alternative pathway during CPB and was activated
      through classic pathway after CPB. The anaphylatoxin, the products of complement
      activation may be responsible for the polymorphonuclear neutrocytopenia.

PMID- 9275703
TI  - Effects of tetrandrine on cardiac noradrenaline release evoked by electrical
      stimulation.
AB  - The effects of tetrandrine (TD) on endogenous cardiac noradrenaline (NA) release
      evoked by electrical stimulation were investigated in perfused guinea pig hearts.
      The overflow of cardiac NA and its intraneuronal metabolite 3,4
      dihydroxyphenylethyleneglycol (DOPEG) were determined by high pressure liquid
      chromatography (HPLC). In the presence of TD, the release of NA evoked by either
      nerve ganglion-stimulation or cardiac field-stimulation was significantly reduced
      (P < 0.01). The overflow of DOPEG was markedly enhanced (P < 0.01). TD inhibited
      cardiac endogenous NA release resulting from activation of the sympathetic nerve
      terminals within the myocardium, and increased the release of DOPEG, indicating
      that TD could result in a loss of NA from storage vesicles or activate monoamine
      oxidase in axoplasma, which could be detected by markedly increased DOPEG
      release. These effects of TD may be associated with its property of calcium
      antagonist.

PMID- 9275704
TI  - Quantitative analysis of glomeruli lesions in patients with mesangial
      proliferative glomerulonephritis.
AB  - By using computer imaging analysis system combined with light microscopy, the
      glomeruli lesions on biopsy specimens sections were quantitatively analysed. The
      pathological changes of mesangial proliferative glomerulonephritis (MsPGN) in
      children were quantitatively evaluated and the correlation between the mesangial
      matrix area (MA) and some clinical data were also analysed. The results indicated
      that the levels of various glomerular parameters in MsPGN group were higher than
      those of normal controls. No correlation was found between MA and 24 h urinary
      protein excretion, but a negative correlation was revealed between MA and
      estimated GFR. MA was also correlated with the duration of MsPGN recovery. It was
      suggested that the quantitative analysis of glomerular parameters by computer is
      a reproducible methods. The parameter of MA may be used for evaluation of the
      renal function, determination of the duration of therapy and evaluation of
      prognosis of MsPGN in children.

PMID- 9275705
TI  - Effect of domestically-made levonorgestrel-releasing intrauterine device on the
      endocrine system and menstruation in monkeys.
AB  - Effect of domestically-made levonorgestrel-releasing intrauterine device (LNG,
      release rate, 6 micrograms/day) on the endocrine system and menstruation in
      monkeys was investigated. The results showed that the Estradiol (E2) and
      progesterone (P) levels were significantly decreased 2 ovulatory cycles after
      insertion of the devices as compared with those before insertion in 3 monkeys (P
      > 0.001), suggesting an evident ovulation-suppressing effect. In 1 monkey, the E2
      and P levels were the same before and after insertion, and expulsion of device
      was found in the monkey later. The plasma LNG concentration in 3 animals was
      493.69-454.60 pg/ml and plasma LNG was not detected in 1 monkey. The hormone
      level returned to normal level after removal of the devices.

PMID- 9275706
TI  - Effects of steroid on diaphragmatic functions in rabbits.
AB  - The effects of steroid on diaphragmatic contractility and endurance were examined
      in 24 New Zealand rabbits. Diaphragmatic contractility was determined by
      measuring gastric pressure (Pga) with the lower thorax and the abdomen of the
      animal being fixed with a rigid cast. Endurance procedure was done by continuous
      15 Hz stimulation of the bilateral phrenic nerves, and diaphragmatic endurance
      was expressed as the time from the initiation of the endurance procedure to the
      moment when transdiaphragmatic pressure 15 Hz (Pdi-15 Hz) decreased to 25% of
      Pdimax-15 Hz. Our data suggested that intravenous administration of dexamethasone
      2.5 mg daily for 7 days did not affect the diaphragmatic contractility
      significantly, but could cause a significant decrease in diaphragmatic endurance.
      When delivered intravenously at the dose of 2.0 mg daily for 14 days,
      dexamethasone induced a significant decrease both in diaphragmatic contractility
      and endurance. The recovery of the diaphragmatic strength from fatigue, however,
      was not influenced by dexamethasone in either circumstance. The influence of
      dexamethasone on diaphragmatic contractility and endurance may have important
      clinical implications.

PMID- 9275707
TI  - Closed anesthesia with nitrous oxide.
AB  - Anesthesia was induced with intravenous thiopental, fentanyl, and
      succinylcholine, and maintained with isoflurane, N2O-O2 and atracurium after
      denitrogenation in 20 adult patients. Inspired and end-tidal concentrations of
      O2, N2O, CO2, isoflurane and oxygen saturation of pulse oximeter (SpO2) were
      monitored. After intubation, N2O (750 ml/min) and O2 (250 ml/min) were
      administrated. When inspired N2O concentration (FiN2O) reached 60% the closed
      anesthesia was initiated by adjusting fresh gas flow rate in order to meet the
      oxygen demand of the patients. The N2O/O2 ratio was constantly kept at 0.7. The
      results revealed that during wash-in period, FiN2O increased, on average, to 30%
      at 3.83 min, 40% at 6.22 min, 50% at 14.13 min respectively. After 30 min of
      closed anesthesia, FiN2O decreased to 49.4%. It was 46.8% at 60 min. Thereafter
      it increased smoothly to 51.9% at 180 min. No hypoxia and hypercapnia occurred.
      Compared with commonly used high flow N2O-N2 inhalation, the technique of low
      flow wash-in and closed circuit maintenance with N2O-O2 may be less expensive and
      feasible and causes less pollution.

PMID- 9275708
TI  - [Mechanism of action of ginsenoside Rb1 in decreasing intracellular Ca2+].
AB  - Using fluorescent probe Fura-2/AM, ginsenoside Rb1 (10, 50 and 100 mumol.L-1) was
      shown to dose-dependently reduce intracellular Ca2+ concentration of freshly
      dissociated brain cells isolated from newborn rats. It was also found to increase
      the fluidity of synaptosome membrane impaired by FeSO4-Cystein. Rb1 (10 mumol.L
      1) shifted the dose-response curve to the right and decreased the maximal
      response in isolated mouse tail artery. Rb1 (10 and 100 mumol.L-1) was also found
      to reduce 5-HT-induced contraction of isolated rat basilar artery. With the whole
      cell patch clamp technique, Rb1 (100 mumol.L-1) was shown to have no obvious
      effect on calcium current and potassium current. However, Rb1 was shown to
      increase Na(+)-K+ ATPase and Ca(2+)-Mg2+ ATPase activities at low dose in rat
      cerebral cortical synaptosomes. The results indicate that decrease of [Ca2+]i by
      Rb1 may be attributed to increase of ATPase activity.

PMID- 9275709
TI  - [Quantitative study on the effect of osthole on proximal tibiae in ovariectomized
      (OVX) rats].
AB  - Thirty-one 3-month-old Female Sprague-Dawley rats were randomly divided into 5
      groups, basal control (group 1, killed at the begining), aging control (group 2),
      ovariectomized (OVX, group 3), OVX with nilestriol treatment group (group 4) and
      OVX with osthole treatment group (group 5). Group 2 and group 3 ig with water 5
      ml.kg-1 and group 5 ig with osthole 6.7 mg.kg-1, all once a day for 6 d; group 4
      ig with nilestriol 1 mg.kg-1, once a week. After 12 weeks, all rats were killed.
      The proximal tibiae of rats were processed to undecalcified sections at 20
      microns thickness for histomorphometric analysis. OVX was shown to reduce
      markedly the trabecular bone mass (%Tb. Ar-59%) due to increase of bone turnover
      with the result that bone resorption exceeded bone formation, as compared with
      aging controls. In contrast, treatment of OVX rats with Osthole and nilestriol
      increased significantly the trabecular area (increased 68% and 27.1% compared
      with that of OVX respectively). Our results indicate that osthole and nilestriol
      treatment provides protection against osteoporosis in OVX rats. The protective
      mechanism of osthole and nilestriol involves supression of bone turnover, but the
      effects of osthole is lower than that of nilestriol (trabecular area decreased
      55% more in osthole group than that with nilestriol treatment). Our finding may
      provide theoretical evidence for the clinical use of osthole or nilestriol for
      treatment and prevention of osteoporosis.

PMID- 9275710
TI  - Effects of m-nifedipine on dihydropyridine binding sites in hypertrophied left
      ventricular cell membranes from deoxycorticosterone acetate-salt hypertensive
      rats.
AB  - m-Nifedipine(m-Nif 20 mg.kg-1.d-1 ig) was administered orally to male
      deoxycorticosterone-acetate-salt(DOCA) hypertensive rats for 9 or 12 wk, the
      affinity and density of dihydropyridines (DHP) binding sites in the membranes of
      left ventricle (LV) were investigated. Treatment with m-Nif, whether for
      prevention (6 wk postoperation) or regression (9 wk postoperation) lowered
      systolic blood pressure, decreased the weight of left ventricle and the Ca2+
      concentration in mitochondria in hypertrophied LV. The density (Bmax) and the
      total number of DHP binding sites in hypertrophied LV were also markedly
      decreased (450 +/- 25, 462 +/- 36 fmol.mg-1 vs 836 +/- 47 fmol.mg-1 protein, P <
      0.001). There was no difference between groups in constant (KD) values of DHP
      binding sites. These results indicate that m-Nif prevented and regressed cardiac
      mass in DOCA hypertensive rats through mechanisms that may be associated with
      their density of DHP binding sites and control of blood pressure.

PMID- 9275711
TI  - [The effects of histamine H2 receptor agonist, antagonist and antineoplastic
      agent on the in vitro growth of PB CFU-GM from normal individuals and HL-60
      leukemia cells].
AB  - Colony forming unit of granulocytes and macrophages from peripheral blood (PB CFU
      GM) represents stem and/or progenitor cells from human blood. In this paper, the
      effects of histamine H2 receptor agonist 4-methylhistamine (4-MH) and its
      antagonist ranitidine (Ranit) on the growth of PB CFU-GM cultured in
      methylcellulose system were studied and their differential effects on normal PB
      CFU-GM and leukemic HL-60 cells were compared with the effect of the
      antineoplastic agent cytosine arabinoside (Ara-C). It was found that the
      histamine H2 receptor agonist 4-MH stimulated the growth of PB CFU-GM when 4-MH
      was added at the concentrations from 10(-9) mol.L-1 to 10(-6) mol.L-1 among which
      the dose 10(-8) mol.L-1 exerted most potent stimulating effect (the PB CFU-GM
      colony numbers was 137.68% +/- 8.20% vs the control, P < 0.01). In contrast, the
      antagonist Ranit showed inhibitory effect on the growth of PB CFU-GM when at the
      concentrations 10(-9)-10(-5) mol.L-1 cultured for 14 d in the same
      methylcellulose system. The inhibition rate was 23.73% +/- 1.16% (10(-9) mol.L-1)
      and 41.42% +/- 6.75% (10(-6) mol.L-1), respectively. Although both Ranit and Ara
      C could inhibit the growth of PB CFU-GM in vitro, Ranit exerted much greater
      inhibition on HL-60 leukemic cells than on normal PB CFU-GM at the dose of 10(-6)
      mol.L-1 (100% inhibition for HL-60 and < 50% inhibition for PB CFU-GM). However,
      the inhibition rate of Ara-C for both HL-60 and PB CFU-GM was 100% at the
      intensive chemotherapeutic dose of 10(-5) mol.L-1. It would appear that the
      histamine H2 receptor agonist 4-MH possesses stimulating effect on the growth of
      PB CFU-GM similar to its effect on CFU-GM from bone marrow as documented before.
      It is suggested that the histamine H2 receptor antagonist Ranit has, to some
      extent, potential in the treatment of myeloid leukemia, especially when combined
      with antineoplastic agent Ara-C at suboptimal doses.

PMID- 9275712
TI  - Chemosensitizing effect of verapamil on Swiss-3T3 cells transfected with human
      MDR1 gene.
AB  - To further understand the characteristics of drug resistance reversal of
      verapamil, the relationship between the level of doxorubicin resistance and the
      magnitude of modulation by verapamil was examined in multidrug resistant Swiss
      3T3 cells transfected with human MDR1 gene. In independently isolated
      transfectants doxorubicin cytotoxicity decreased markedly compared with parent
      cells. Potentiation of doxorubicin toxicity by a noncytotoxic concentration of 3
      mumol.L-1 of verapamil was much greater in transfectants than in parent cells,
      while the magnitude of reversal was inversely dependent on the level of
      resistance. Southern blot hybridization indicated the MDR1 cDNA integration in
      genomics of each transfectant. Defect in cellular accumulation of doxorubicin was
      restored by verapamil in transfected cells. The saturation of active drug
      transport that may involve the magnitude changes of potentiation by verapamil,
      and the mode of interaction between P-glycoprotein and drugs, were discussed.

PMID- 9275713
TI  - [Enzyme kinetic studies on the in vitro metabolism of omeprazole by Chinese human
      liver microsomes].
AB  - In the present study, a specific and reliable method was developed for the
      determination of omeprazole and its two major metabolites, hydroxyomeprazole (OH
      OPZ) and omeprazole sulfone (OPZ-SFN) in Chinese adult human liver microsome by
      reversed phase HPLC assay. Formation of these metabolites is linear for at least
      60 min and between 0.25 and 1 mg.ml-1 of microsomal protein. The enzyme kinetic
      analysis of the reaction revealed that the hydroxylation Vmax and K(m) obtained
      with the human liver microsomal preparation were 42.9 nmol.min-1.(mg protein)-1
      and 6.49 mumol.L-1, respectively. The maximum formation rates of OPZ-SFN (Vmax)
      was 6.63 nmol.min-1.(mg protein)-1, with a K(m) value of 11.8 mumol.L-1. A number
      of compounds were tested for their ability to inhibit OPZ metabolism. Our results
      showed that mephenytoin, diazepam and nordiazepam are competitive inhibitors and
      papaverine is an uncompetitive inhibitor of OPZ hydroxylation. These studies
      suggest that the same isozyme metabolising MP, DZ and NDZ (may be P450 2C or P450
      3A) may be involved in the hydroxylation of OPZ. Moreover, the compounds tested
      also have some effects on the formation of OPZ-SFN in vitro with Chinese human
      liver microsomes.

PMID- 9275714
TI  - [Studies on peptide. XIX: Hepatitis C virus (HCV) immune selection].
AB  - HCV has characteristics of rapid variability. The amino terminus of E2/NS1 of HCV
      (amino acids sequence 384-414), which is hypervariable with respect to both
      nucleotide and amino acid sequence, has been termed the E2 HV domain or HVR1. The
      E2 HV domain appears to be a rapidly evolving region of the HCV genomes which may
      contain linear neutralizing epitopes and the E2 HV are under immune selection.
      For further studies of the immunogenicity on E2 HV of HCV, we selected three
      peptide fragments from the full length of E2 HV region sequence and synthesized
      them with SPPS method. The amino acid sequences are shown as following: P2:
      VDGDTHVTGGAQAKTTNR (381-398); P9: STHVTGAVQGHSIRGTTSLFTSGPAQKIQ (384-412); P10:
      RTYTSGGTAGHTTSGITSLFSPGASQKIQ (384-412). From the results of ELISA and anti
      peptide Abs of rabbit sera, we conclude that there are anti-E2 HV Abs in immune
      host but they could not neutralize HCV, so these Abs were not reactive with all
      E2 HV epitopes that resulted in immune selection of escape mutants; the anti-E2
      HV Abs, probably from the same genotype, contained some common structure in which
      E2 HV epitopes react with other anti-E2 HV Abs at 30%: the C-terminus of E2 HV
      region (398-412) caused the immune response to rabbits.

PMID- 9275715
TI  - [Determination of azathiopurine concentration in human serum by second derivative
      spectra method].
AB  - A sensitive and rapid method for the determination of azathiopurine concentration
      in human serum was established. By using ultraviolet second derivative spectra,
      the method eliminated background interference of biological sample and coexisting
      drugs. The serum sample was extracted with ethyl acetate, the extract was
      evaporated to dryness with a gentle N2 stream, and 0.25 ml of methanol was added
      to dissolve the residue. Quantitative calculation was made with analytical
      wavelength of 274 nm and 293 nm, and peak- to- valley method. The minimum
      detectable concentration of AZP in serum was 25 ng.ml-1 and average recovery was
      99.3% +/- 5.9%.

PMID- 9275716
TI  - [Increase of gentamicin uptake in cultured mouse peritoneal macrophage and rat
      hepatocytes when used in the form of nanoparticles].
AB  - The polybutylcyanoacrylate nanoparticles of 3H-labeled gentamicin were prepared
      in order to investigate the possibility of gentamicin nanoparticles as an
      intracellular drug delivery system for intracellular chemotherapy. The 3H-labeled
      gentamicin nanoparticles were incubated with mouse peritoneal macrophage (MPM) or
      rat hepatocytes (RH) for some period, then the cells were separated from the
      nanoparticles, and finally the radioactivity (cpm) of 3H in the cells were
      measured by a liquid scintillation counter. By comparison with the solution of 3H
      labeled gentamicin, a 6.34 times increase of cpm value in MPM after 30 min
      incubation, and 27.74, 9.03 and 8.36 times increase of MPM values in RH after 1,
      12, and 24 h incubation respectively, were observed by binding gentamicin with
      polybutylcyanoacrylate nanoparticles. The particle size, surfactant coating,
      stabilizer and the gentamicin concentration were found to have some effect on the
      uptake of nanoparticles by two kinds of cells. This study provided a basis for
      the screening of intracellular drug delivery system.

PMID- 9275717
TI  - [Effects of 2-(p-dimethylaminostyryl) pyridine methycholide (DSPM-Ci) on ECG,
      left atrium contractivity and on papillary muscle action potentials].
AB  - The effects of DSPM-Cl on ECG in rats, on the dose-effect curve in guinea pig
      left atria and on the fast action potential (AP), high-K+ depolarized slow action
      potential (SAP) in guinea pigs papillary muscle were examined
      electrophysiologically. DSPM-Cl (2 mg.kg-1) showed significant nagative
      frequency, negative conductivity effect, and prolonged the PP and PR interval.
      DSPM-CI (30-50 mumol.L-1) was shown to inhibit left atria contractility and shift
      the concentration-response curve of Iso and CaCl2 to the right with PD2' values
      of 4.60 and 4.13, respectively. In addition, DSPM-Cl was found to prolong the
      duration of action potential 90 (APD90) and effective refractory period (ERP),
      and decrease the maximal upstroke velocity (Vmax) in K(+)-depolarized guinea pigs
      papillary muscles. The results suggest that, like verpamil, DSPM-Cl might be a
      calcium antagonist.

PMID- 9275718
TI  - [Study on pharmacokinetics of human granulocyte-macrophage colony stimulating
      factor (hGM-CSF) in rats using a sensitive immunoassay (ELISA)].
AB  - A sensitive and reliable sandwich enzyme linked immunosorbent assay (ELISA) has
      been developed for determination of concentration of recombinant human
      granulocyte-macrophage colony-stimulating factor (hGM-CSF). The assay is
      quantitative between 0.39-12.5 ng.ml-1 for bacterially synthesized hGM-CSF in rat
      serum and urine. The method was shown to be highly specific and did not
      significantly alter the determination when adding some potential interfering
      substances. After single sc injection of hGM-CSF 50, 100 or 200 micrograms.kg-1,
      a high hGM-CSF level was detected about 15 min in rat serum, the highest level of
      hGM-CSF was two apparent phases with half-lives T1/20 of 0.72, 0.70, 0.80 h and
      T1/28 of 8.77, 8.87 and 5.58 h. A detectable urinary excretion occured after sc
      injection of hGM-CSF 200 micrograms.kg-1, but the total urinary excretion of
      unchanged hGM-CSF was very low.

PMID- 9275719
TI  - [Protein kinase inhibitor staurosporine enhances cytotoxicity of antitumor drugs
      to cancer cells].
AB  - Treated with low dosage (5 ng.ml-1) of staurosporine for 18 h, human embryo lung
      2BS cells were blocked at the G1/S boundary, but human gastric carcinoma BGC-823
      cells still kept their cell cycle. In comparison with IC50 of 2BS and BGC-823
      cells treated with cell cycle phase specific antitumor drugs adriamycin, Ara-C
      and BLM A5 alone or combined with staurosporine 5 ng.ml-1, the IC50 values
      increased from 0.325 microgram.ml-1, 5 micrograms.ml-1 and 6.5 micrograms.ml-1 to
      0.45 microgram.ml-1, 10 micrograms.ml-1 and 6.5 micrograms.ml-1, respectively in
      2BS cells; but decreased from 0.325 microgram.ml-1, 25 micrograms.ml-1 and 1.1
      micrograms.ml-1 to 0.07 microgram.ml-1, 6.25 micrograms.ml-1 and 0.4 microgram.ml
      1, respectively in BGC-823 cells. These results suggest that combination of
      staurosporine 5 ng.ml-1 with antitumor drugs showed different effects on tumor
      cells and normal cells. With the GSH fluorescent probe mBCL, we found that GSH
      contents increased in 2BS cells treated with staurosporine 5 ng.ml-1.

PMID- 9275720
TI  - [Effects of blastocyst deficiencies induced by aspirin treatment during
      preimplantation period in rats on development of embryos after implantation].
AB  - Pregnant rats were treated orally with aspirin 0.5 or 1.0 g.kg-1 on d 3 (positive
      vaginal smear was considered as d 0) and were sacrificed on d 4. Some blastocysts
      collected on d 4 were evaluated for gross morphology and cell number, and the
      remainings were transfered into pseudopregnant rats. Results showed that the rate
      of blastocysts with abnormal morphology were 23.8% and 40.8%, respectively, in
      0.5 and 1.0 g.kg-1 of aspirin. These were significantly higher than 6.8% of the
      control group. The cell number of blastocysts also decreased in the aspirin
      groups. The rate of implantation and live fetuses in the case of blastocysts with
      normal morphology were related negatively with the aspirin doses, espesially in
      the group of 1.0 g.kg-1 of aspirin, the implantation rate was significantly lower
      (38.6%). However, the implantation rate of blastocysts with abnormal morphology
      in both groups of aspirin were much less than that of the control group, and all
      embryos after implantation were resorped. No significant malformations were
      observed in the live fetuses. These results suggests that the effects of
      blastocyst deficiencies induced by aspirin on development of embryos transfered
      into pseudopregnant rats mainly caused death of embryos, but not malformation of
      fetuses.

PMID- 9275721
TI  - [An animal model for screening of antiallergic and antipruritic drugs].
AB  - 4-Aminopyridine(4-AP) 1 mg.kg-1 sc at the scruff induced a licking response in
      mice. Antiallergic and antipruritic drugs, such as diphenhydramine HCl(20 mg.kg-1
      ip), doxepin(12.5 mg.kg-1 ig), prednisone(10 mg.kg-1 ig), dexamethasone(10 mg.kg
      1 ip), fluocinolone (applied to the surface of skin), Pi Yan Ping(applied to the
      surface of skin), disodium cromoglicate(400 mg.kg-1 ip), ketotifen(1 mg.kg-1 ip),
      etc. markedly inhibited the licking response elicited by 4-AP. The calcium
      antagonist nifedipine(500 mg.kg-1 lg) and the potassium channel opener
      minoxidil(400 mg.kg-1 ig) produced the same inhibitory effect. H2-receptor
      antagonist cimetidine(200 mg.kg-1 ip) and ranitidine(150 mg.kg-1 ip) showed no
      effect. Morphine HCl(10 mg.kg-1 ip) and diazepam(0.02 mg.kg-1 ip) exhibited
      antagonistic effect on the licking response induced by 4-AP, but phenobarbital(25
      mg.kg-1 ip), pentobarbital(15 mg.kg-1 ip) and aspirin(300 mg.kg-1 ig) did not.
      These results indicate that many antiallergic or antipruritic drugs inhibited the
      licking response induced by 4-AP. The method of licking response elicited by 4-AP
      has the merit of simplicity and convenience and may be used for screening
      antiallergic and antipruritic drugs.

PMID- 9275722
TI  - [Synthesis and antimicrobial activities of tetrahydro-2H-1,3,5-thiadiazine-2
      thiones].
AB  - Ten 3-benzyl-5-substitued tetrahydro-2H-1,3,5-thiadiazine-2-thiones were
      synthesized and seven of them are reported for the first time. The structures of
      the compounds have been elucidated by UV, IR, H-NMR and elemental analysis. The
      in vitro activity of the compounds against 6 kinds of bacteria and 2 kinds of
      fungi was tested. The antimicrobial activities of all compounds are more potent
      than sulfadiazine sodium and less potent than norfloxacini. All compounds were
      found to be more active against gram-negative and less active against gram
      positive bacteria and weak against fungi.

PMID- 9275723
TI  - [Studies of chemopreventive agents against neoplasma: synthesis of 3-acetyl
      coumarin derivatives and relationship between antimutagenic activity and
      structure].
AB  - Twenty-five 3-acetylcoumarin derivatives were synthesized among which twenty-two
      were not reported before. Antimutagenic activity screen in vitro has shown that
      some of these compounds have various activities. The structure and activity
      relationship for 5-, 7-, 8-substituents has been studied. Pharmacological data
      showed that: the substituent on position 8 has important effect on its activity.
      When there is only a hydroxy group on position 7, its activity is the highest
      among those with other substituents, but when a methyl is on position 8, the
      order of the activity is reversed. Other trends have also been found which
      provided some clues for further structural modification.

PMID- 9275724
TI  - [Effect of membrane modification by PEG on prolongation of circulation time of
      liposomes in blood in vivo].
AB  - PEG-PE (polyethylene glycol-phosphatidyl ethanolamine) of different molecular
      weight (2000 and 5000) were used to modify the membrane of liposomes. Large
      unilamellar liposomes containing PEG-PE were prepared by reversed phase
      evaporation. Fluorescent label-calcein was encapsulated at the internal water
      phase. To compare the differance between the modified and unmodified membrane,
      the stability in vitro and distribution in vivo were investigated. The results
      indicated that the circulation half-life for liposomes unmodified, modified by
      PEG (2000)-PE and modified by PEG (5000)-PE were 13, 21 and 75 (min)
      respectively. At 6 h after injection, the ratio b/R (b: distribution in blood, R:
      distribution in liver and spleen) were 0, 0.8 and 1.4, respectively. The results
      mean that the stability increased and circulation time was prolonged by the PEG
      PE modified membrane. The effect of PEG-PE on membrane was found to be directly
      proportional to the chain length of the polymer.

PMID- 9275725
TI  - [Studies on metabolism of 6-chloro butyl phthalide by rat liver microsomes].
AB  - The in vitro metabolism of 6-chloro-butyl phthalide (CBP) was studied by rat
      hepatic microsomes. The constitution of the incubation system was optimized and a
      RP-HPLC-DAD method was developed for the on-line analysis of CBP and its
      metabolites. The difference of the metabolism profiles of CBP by rat liver
      microsomes induced by phenobarbital (PB) and 3-methylcholanthrene (3-MC) was also
      compared. TLC, column chromatography and preparative HPLC were used for the
      isolation and purification of the major metabolites and they were identified as
      (R/S) gamma-hydroxy-CBP and (R/S) beta-hydroxy-CBP by UV, NMR and MS.

PMID- 9275727
TI  - [Building up of an animal model of conditioned immunosuppression and analysis of
      its possible mechanism].
AB  - In the present study, camphor odor and intraperitoneal (ip) injection of
      cyclophosphamide (CY) were used as conditional and unconditional stimulus,
      respectively, in mice. Mice were exposed to camphor odor for 1 h in their cage in
      a closed area followed by an ip injection of CY (75 mg.kg-1). This association
      trial session was repeated once on the next day. Delayed type hypersensitivity
      response (DTH) was induced as follows: six days after the second association
      trial session the mice were sensitized by smearing dinitrochlorobenezene (DNCB)
      on their abdominal skin. The mice were challenged by smearing DNCB on the left
      ear 5 days after the antigen sensitization. The left and right ears were removed
      24 h after the challenge and weighed, the weight ratio of left/right ears was
      calculated for identification of the response. The ratio was 1.30 +/- 0.113 (+/-
      s, P < 0.001), indicating that the challenged ear was heavier than the other and
      DTH was induced. In the unconditioned response (UCR) group, CY (75 mg.kg-1) was
      given 24 h prior to the challenge and the ratio was 1.09 +/- 0.024 (P < 0.001)
      indicating that DTH was suppressed by unconditional stimulus (CY). In the
      conditioned response (CR) group mice were reexposed to camphor odor 24 h prior to
      the challenge and normal saline was injected instead of CY. The ratio was 1.13 +/
      0.074 (P < 0.001), indicating that DTH was also suppressed by conditional
      stimulus (camphor odor). These results show that a conditioned immunosuppressive
      response was induced. In the experiment, many other groups, including
      unconditioned response group, CYE group and camphor control group, were described
      in more details in the text. In order to further analyse the mechanisms of the
      conditioned response, the blood from the mice in CR group was obtained 6 h after
      reexposure to camphor odor and the serum was injected to normal mice 6 h prior to
      the challenge. DTH was found to be suppressed significantly when compared with
      the mice injected with normal serum. The conditioned serum was dialyzed against a
      membrane with a 10,000 molecular weight cut off. The suppressive activity of the
      conditioned serum disappeared, suggesting that the molecular weight of the
      suppressive element in the serum was probably less than 10,000 kDa.

PMID- 9275726
TI  - [Isolation and amplification of DNA from tortoise and turtle shells].
AB  - DNA was extracted from tortoise and turtle shells, two Chiense crude drugs which
      have been preserved for at least nine years. The cytochrome b sequence was
      amplified from the extracts using the polymerase chain reaction. Treatments with
      detergent and ultraviolet light were employed to destroy possible extraneous
      contamination. A control extract was set in parallel with the extracts of the
      specimens in order to detect contamination in solutions and reagents. The results
      show that significant amounts of genetic information can survive in the shells
      and may have important implications for their identification.

PMID- 9275728
TI  - Expression of mesenger RNA for transforming growth factor-beta 1 in bovine
      trabecular meshwork.
AB  - PURPOSE: To investigate the relationship between transforming growth factor-beta
      1 (TGF-beta 1) and primary open-angle glaucoma, we have determined whether
      trabecular tissues have the expression of messenger RNA for TGF-beta 1. METHODS:
      Total RNA of 24 newborn bovine trabecular tissue were extracted by Guanidine
      isothiocyanate method. The TGF-beta 33 plasmid was brought into E. colibacillius
      HB101 and amplificated. After Bam HI endolase degradation and label with alpha
      32p-dATP the RNA was hybridized with the cDNA (complementary DNA) probe and
      examined by autoradiography. RESULTS: The presence of mRNA for TGF-beta 1 in
      bovine trabecular meshwork was confirmed. CONCLUSIONS: The TGF-beta 1 present in
      normal aqueous humor must be at least partly derived from the trabecular
      meshwork. It offered a basis for understanding the relationship between abnormal
      synthesis, activation and clearance of TGF-beta 1 and the pathogenesis of primary
      open-angle glaucoma (POAG) in molecular biology.

PMID- 9275729
TI  - Single 5'green-3'red hybrid gene in protanopia.
AB  - PURPOSE: To disclose the structure of visual pigment gene for a protanopia with
      specific variation. METHODS: Exon 5 fragments of the red and green visual pigment
      genes from the protanopia with specific variation as well as controls were
      amplified by polymerase chain reaction (PCR). The PCR products were put through
      heteroduplex-SSCP analysis and PCR-RFLP (restriction fragment length
      polymorphism) analysis to clarify the specific variation. The specific variation
      of the exon 5 DNA fragment from the protanopia was identified by sequencing.
      RESULTS: A novel 5'green-3'red hybrid gene fragment without the normal red and
      green visual pigment gene was discovered in the protanopia. He should only have a
      single visual pigment gene, 5'green-3'red hybrid gene, on his X chromosome. The
      fusion point is between codon 285 and codon 296 in exon 5. CONCLUSION: Unequal
      intragenic recombination may occur in exon 5 as well as its upstream. A 5'green
      3'red hybrid gene may present independently on the X chromosome without
      accompanying the red or green visual pigment gene. Single visual pigment gene
      with 5'green-3'red hybrid fragment of exon 5 could express function which is
      similar to the green pigment gene. This example also gives in vivo evidence that
      codons 277 and 285, rather than codon 309, play a major role in tuning the
      absorption spectra of the red and green visual pigments.

PMID- 9275730
TI  - An immunohistochemical study of IgG, complement C3, collagen type III and
      macrophage-marker Ki-M7 in epiretinal membranes.
AB  - PURPOSE: To observe the immunological changes in epiretinal membranes from the
      patients with proliferative vitreoretinopathy (PVR). METHODS: Twelve samples of
      epiretinal membranes obtained during vitreous surgeries for PVR were examined by
      direct and indirect immunofluorescein histochemistry. RESULTS: The cellular
      membranes in 8 cases were composed of retinal pigment epithelial cells,
      fibroblast-like cells, macrophages and collagen. Positive stainings of IgG, C3+
      collagen type III and macrophage-marker Ki-M7 (CD68) was seen in the membranes.
      CONCLUSION: The results indicate that humoral immune components and macrophages
      may play an important role in the development of epiretinal membrane formation.

PMID- 9275731
TI  - Immunohistochemical studies of macrophages and MHC class II-positive cells in the
      iris and ciliary body of Lewis rats.
AB  - PURPOSE: To investigate the density, distribution and morphology of macrophages
      and MHC class II-positive dendritic cells in the iris and ciliary body of lewis
      rats. METHODS: Immunohistochemistry was performed using monoclonal antibodies
      specific to monocytes and macrophages (ED1, ED2) and MHC class II-positive cells
      (OX6) on wholemounts of the iris-ciliary body complex isolated form normal lewis
      rats. RESULTS: A well developed network of macrophages was present in the iris
      and ciliary body of normal lewis rats. These cells, morphologically displaying
      dendritiform or pleiomorphic appearance, were more densely arranged in mid-iris
      (950 +/- 189 cells/mm2) than in iris base (482 +/- 78 cells/mm2) and pupil margin
      (595 +/- 92 cells/mm2). A similar network of MHC class II-positive cells with a
      cell density 452 +/- 78 cells/mm2 was almost uniformly distributed in the iris of
      normal lewis rats. CONCLUSIONS: A network of macrophages and MHC class II
      positive cells was established in the iris and ciliary body of normal lewis rats.
      These cells may be involved biologically in the generation of anterior chamber
      associated immune deviation-inducing signal within the anterior chamber and the
      transferring of this signal from the eye to the spleen, and pathophysiologically
      in the pathogenesis of uveoretinitis.

PMID- 9275732
TI  - Lysosomal enzyme activities in cultured retinal pigment epithelial and glial
      cells of RCS rat.
AB  - PURPOSE: To compare the activities of acid phosphatase, N-acetyl-beta
      glucosaminidase and alpha-mannosidase in cultured retinal pigment epithelium
      (RPE) and glial cells of Royal College of Surgeons (RCS) rat with those in Long
      Evans (LE). METHODS: The cultured RPE and glial cells of RCS and LE rat were
      plated into the same 96 well microtitre, and the biochemical method in
      microsystem were used for enzyme assays. RESULTS: The activities of acid
      phosphatase and N-acetyl-beta-glucosaminidase are higher by, respectively, 30%
      and 46% in cultured RPE of RCS rat than LE rat. The activity of alpha-mannosidase
      has no significant difference. The activities of 3 enzymes in the retinal glial
      cells derived from RCS rats are higher than LE rat by 13% to 77%. CONCLUSION:
      These results suggest that the high activities of lysosomal enzymes in RCS RPE
      and glial cells may play an important role in the pathogenesis of retinal
      dystrophy.

PMID- 9275733
TI  - Macrophages in human epiretinal and vitreal membranes in patients with
      proliferative intraocular disorders.
AB  - PURPOSE: Macrophages are versatile cells and have been known as a cellular
      component of epiretinal membranes of proliferative intraocular disorders (PID).
      However, the origin and functions of these cells in the membranes are not yet
      clear. In the present study we investigated the characterization of
      macrophages/monocytes in various types of human epiretinal membranes from
      patients with proliferative vitreortinopathy (PVR), proliferative diabetic
      retinopathy (PDR) and ocular perforating injury by means of immunohistochemical
      techniques. METHODS: A total of 49 epiretinal membranes of PID in which 24 were
      PDR specimens, 17 were PVR and 8 were proliferations after perforating eye injury
      were studied. Monoclonal antibodies against human macrophages, monocytes, HLA-DR
      antigen and interleukin-1 (IL-1) were used. The alkaline phosphatase anti
      alkaline phosphatase (APAAP) technique was performed. RESULTS: The results showed
      that 19 out of 24 PDR specimens (79%), 15 out of 17 PVR specimens (88%) and 7 out
      of 8 traumatic specimens (87%) contained macrophages, HLA-DR antigen was detected
      in 20 out of the 24 PDR membranes (83%), 14 out of 17 PVR membranes (82%) and 5
      out of 8 traumatic membranes (63%); monocytes were only detected in 10 out of the
      24 PDR specimens (41%). In addition, in a group of PDR specimens, interleukin-1
      (IL-1) was detected in 8 out of 13 tested specimens (62%). CONCLUSION: The
      results revealed that the macrophages in the membranes were in an active stage
      and may play a significant role in the development of proliferative intraocular
      disorders through either inducing inflammatory reactions or immune responses, or
      the effects of their cytokines.

PMID- 9275734
TI  - Changes in local immune functions in Mooren's ulcer.
AB  - PURPOSE: To the investigate changes in local immune functions of the cornea and
      the adjacent conjunctiva, and their roles in the mechanism of the disease.
      METHOD: The cornea and adjacent bulbar conjunctiva taken from 14 patients with
      Mooren's ulcer were stained immunohistochemically for CD3, CD4, CD8, HLA-DR, CD1
      and CD25. RESULT: An aberrant expression of HLA-DR antigen by a large number of
      kerato-conjunctival epithelial cells and keratocytes in the corneal stroma was
      found. The CD4+/CD8+ ratio is significantly higher than normal control.
      CONCLUSION: The aberrant expression of MHC-II antigen in the resident cells at
      the peripheral cornea and the adjacent conjunctiva, along with a raised local
      TH/Ts ratio leading to an excessive autoimmune reactivity is possibly the direct
      cause of Mooren's ulcer.

PMID- 9275735
TI  - Development of the scale of quality of life for diseases with visual impairment.
AB  - PURPOSE: To describe the development of the of scale quality of life which can
      measure the quality of life of Chinese patients with visual impairment. METHODS:
      Based on a thorough literature search and consultation with ophthalmologists and
      public health professionals, 20 items were selected to create a scale. Fifty
      seven cataract patients with vision impairment and 60 glaucoma patients with
      vision impairment and visual field loss were measured by the scale to evaluate
      the validity, reliability and responsiveness of the scale. RESULTS: The scale
      covered four domains of the quality of life (QOL). The criterion related validity
      of the scale: r = 0.6865 (P = 0.001). The test-retest reliability of the scale: r
      = 0.8959 (P = 0.001). Coronback's alpha was 0.9359. The variance ratio (VR) of
      intra-individual variance to inter-individual variance was 0.0551 for overall
      scores. The correlation coefficient of split-half method was 0.9553. The
      responsiveness: T-test, T = 5.95 (P = 0.001), effect size statistic was 1.533.
      CONCLUSIONS: The result demonstrates that the scale has a satisfactory validity,
      reliability and responsiveness. It suggests that the scale can be applied to
      clinical trials.

PMID- 9275736
TI  - Local electroretinogram and pattern visual evoked potential in maculopathies.
AB  - PURPOSES: To observe the characteristics of local electroretinogram (LERG) in
      normal subjects and patients with maculopathies, and to evaluate the applied
      worth of LERG and pattern visual evoked potential (PVEP) in maculopathies.
      METHODS: LERGs at 5 degrees and 15 degrees macular regions were recorded from 27
      normal subjects (54 eyes). The factors of age, different eyes and stimulate areas
      for LERG influence were observed. Meanwhile, the LERG and PVEP were recorded from
      25 patients (35 eyes) with maculopathies for making contrast study. RESULTS: In
      normal subjects, there was no significant influence of age to LERG. As the
      stimulated areas increased, the a- and b-wave amplitudes of LERG increased. In
      the patients with maculopathies, the a- and b-wave amplitudes of LERG at 5
      degrees, 10 degrees and 15 degrees macular regions were significantly lowered and
      the mean values of P1 latency were prolonged and N1-P1 amplitudes of VEP were
      lowered, comparing with the control group. In the nearing stimulated area (5
      degrees LERG and 14.9 x 19 degrees PVEP), there were no significant differences
      of the abnormal rates of both LERG and PVEP. CONCLUSION: There are close
      sensitivities of testing the function of macular region with LERG and PVEP in
      maculopathies. However, LERG is not influenced by the visual path diseases and
      visual acuity, it is a more effective and direct way than PVEP in measuring
      macular function.

PMID- 9275737
TI  - A study of motion perception in primary open angle glaucoma.
AB  - PURPOSE: To study the features of the motion perception (MP) and explore the
      worth of the clinical application of MP test in primary open angle glaucoma
      (POAG). METHODS: MPs were recorded from 41 patients (67 eyes) with POAG ang 56
      normal subjects (112 eyes) by the MP software in PC compatible computer.
      Meanwhile, the MP ways and MP sites were analyzed and MP abnormal rate was
      compared to the clinical parameters and the visual function indices related to
      glaucoma. RESULTS: The results showed that the total abnormal rate of MP was
      89.5% in POAG, and the abnormal rate was 81.6% in early stage of POAG, and MP
      abnormal degree had positive correlation with C/D, ocular tension and corrected
      loss variance (CLV), and negative correlation with visual acuity and mean
      sensitivity (MS), and no correlation with age and short-term fluctuation (SF) in
      the patients with POAG. CONCLUSION: These results suggest that the MP test
      provides a newly effective examination method in diagnosing the early POAG.

PMID- 9275738
TI  - [A role of oblique flashlight test in screening for primary angle closure
      glaucoma].
AB  - PURPOSE: To study the effect of oblique flashlight test in screening for primary
      angle closure glaucoma. METHOD: Two hundred adults over 50 years old were sampled
      randomly at Doumen county of Guangdong province in 1995. 390 eyes were measured
      by oblique flashlight test according to grading standard photos of oblique
      flashlight test. Other ocular examinations consisted of intraocular-pressure
      measurement with Schiotz tonometer, gonioscopy, and optic disc appearance.
      RESULTS: The result showed 25.2% of the examined eyes had the oblique flashlight
      grade < or = 2, and tended to be increasing with age (x2 = 8.597, P < 0.05) and
      in females (x2 = 14.89, P < 0.01). Based on temporal anterior chamber angle < or
      = 2 (Shaffer's grade), the obligue flashlight grade < or = 2 found that
      occludable angle sensitivity was 91.7%, specificity was 91.5%, and 8.16% of the
      eyes had primary closure angle glaucoma. No patient was found in oblique
      flashlight grades > or = 3. CONCLUSION: This study shows that oblique flashlight
      test conforms to screening test needs, and plays an important role in screening
      for primary closure angle glaucoma. We suggest that oblique flashlight grades <
      or = 2 as cutoff point of screening for occludable angle.

PMID- 9275739
TI  - [Method of designing a mold for processing corneal lenticules in epikeratophakia
      with excimer laser].
AB  - PURPOSE: To design a mold for processing optical power in epikeratophakia.
      METHOD: With excimer laser a corneal graft with appropriate optical power shall
      be got on the formula of the mold's radius curvature. RESULTS: Based upon the
      formula from the data, a 12D mold was accomplished to obtain a suitable cornea
      lens for epikeratophakia. CONCLUSION: The 12D mold presents the value to some
      extent in processing the desired optical power of corneal graft for those
      patients requiring epikeratophakia.

PMID- 9275740
TI  - [Detection of herpes viral genome in corneal buttons of quiescet herpes simplex
      keratitis with polymerase chain reaction].
AB  - PURPOSE: Herpetic keratitis is one of the major cause of blindness. The recent
      reports have proposed that the herpetic viruses may persist in cornea but
      provided noconclusive evidence. This study is to determine whether the cornea is
      another latent site of herpes simplex virus. METHODS: 18 corneal buttons of
      patients with quiescent herpes simplex keratitis which had quited for at least
      three months (mean 3.7 years) and were obtained by corneal transplantation were
      detected using polymerase chain reaction (PCR). The sequences of the primers are:
      P15'CATCACCGACCCGGAGAGGGAC, P25'GGGCCAGGCGCTTGTTGGTGTA. RESULTS: The positive HSV
      DNA were found in 17 corneal buttons out of 18 cases. CONCLUSION: The HSV genomes
      are present in the cornea of quiescent herpetic keratitis, which suggest that the
      cornea may be another latent site of herpetic virus. The PCR is a simple,
      specific and sensitive way to detect HSV genomes in cornea.

PMID- 9275741
TI  - [Observation of corneal endothelial cells in modified mid-term preservation by
      scanning electronic microscope].
AB  - PURPOSE: To observe the ultramicroscopic structure of corneal endothelium in
      modified mid-term preservation. METHODS: Eyes of 4 New Zealand rabbits were
      enucleated. The 4 right eyes and additional 6 human eyes (as experiment group)
      were treated as follows: Aqueous was drawn off and replaced with equal volume of
      C3F8 air, then the whole eye was preserved in wet chamber at 4 degrees C, with 2
      rabbit eyes being preserved for 7 days. 1 for 10 days and 1 for 14 days, and 6
      human eyes for 0, 3, 5, 7, 10 and 14 days respectively. Corneas with 1 mm scleral
      ring of the 4 rabbit eyes (control group) were derived and preserved in Optisol
      nutrients at 4 degrees C for the same period of time. Corneas of all eyes were
      examined by scanning electronic microscope. RESULTS: For rabbit eyes, slight
      edema was found in the cornea preserved for 7 days, and loss of surface
      microvilli and cell lysis were found in those preserved for 10 and 14 days. For
      human eyes, no significant change was found in cornea preserved for 7 days, and
      different changes were found in those preserved longer. CONCLUSION: No
      significant change was found in cornea endothelium preserved by this method for 7
      days.

PMID- 9275742
TI  - [Clinical study on allogenic conjunctival transplantation].
AB  - PURPOSE: To investigate the indications and outcome of human allogenic
      conjunctival transplantation. METHODS: The necrotic tissues and scars were
      removed from the fornix by using the residual conjunctiva. Then the allograft
      without Tenon's capsule was transplanted to cover the wound. RESULTS: At 6
      postoperative months, the surface was completely healed in 76%x. For patients
      with mechanical trauma or thermal burn, the area of transplanted conjunctiva was
      less than one third, or using donor conjunctiva from parents or siblings are of
      better prognossis. CONCLUSIONS: 1) Allogenic conjunctival transplantation is a
      feasible treatment for servere symblephron and lid defects. 2) The result is poor
      when residual conjuctiva is less than 1/2. 3) The outcome is best in mechanical
      trauma and worst in alkaline burns, with thermal burns somewhere in between. 4)
      The simple bulbal conjunctival transplantation has better results.

PMID- 9275743
TI  - [Effect of homoharringtonine on lens epithelial cells in rabbits].
AB  - PURPOSE: To study the effects of Homoharringtonine (Hh) on lens epithelial cells
      (LEC) in rabbits for the possibility of preventing or treating the development of
      after cataract. METHODS: Lens epithelial cells from the right eyes of 9 New
      Zealand Albino rabbits were processed for light microscope and transmission
      electronic microscope 30 minutes, 3 days and 60 days after phacoemulsification by
      the use of Hh (20 micrograms/ ml) in balanced salt solution (BSS) as irrigating
      solution. LEC from the left eyes of the same rabbits served as controls after
      phacoemulsification by the use of BSS. Clinical examinations were also performed
      in all eyes before and after the surgery. RESULTS: Hh as irrigating solution
      during phacoemulsification had antiproliferative effects on LEC 3 days
      postoperatively, the Hh treated eyes developed less LEC proliferation than the
      controls. Though the development of after cataract formation (Soemmering ring)
      could not be prevented in both Hh treated eyes and controls 60 days after
      phacoemulsification, the ultrastructural study of LEC from the Hh treated eyes
      indicated some changes of cytoplasm such as vacuolation of organelles.
      CONCLUSION: It is suggested that increasing the concentration of Hh in irrigating
      solution for phacoemulsification and prolonging the existence of Hh in aqueous
      humor may have more effects on the inhibition of the proliferation of LEC. From
      the results of this preliminary study a pharmacological means of prevention and
      treatment of after cataract may be indicated.

PMID- 9275744
TI  - [Study on human gamma-crystallins: V. Non-enzymatic glycation of fetal lens gamma
      1- and gamma 3-crystallins in vitro].
AB  - PURPOSE: To compare the non-enzymatic glycation of different human fetal gamma
      crystallins induced by glucose and fructose. METHODS: gamma 1- and gamma 2
      crystallin were separated by the Sephadex gel chromatography from human fetal
      lenses. The non-enzymatic glycations of these gamma-crystallins were conducted by
      incubating with glucose or fructose at 37 degrees C for 20 days. The opacity and
      pellet formation as well as changes on SDS-polyacrymide gel electrophoresis (SDS
      PAGE) pattern and blue fluorescence production were observed. RESULTS: Although
      the two gamma-crystallins displayed similar alterations, gamma 1-crystallin was
      easier to produce aggregation and insolublization in early stage (i.e. 3 days).
      SDS-PAGE showed that there were aggregates, formed through disulfide and non
      disulfide cross-links, and degraded peptides produced. The blue fluorescence
      increased in glycated gamma 3-crystalline solution. Fructose had more significant
      effects (i.e. aggregation, degradation, producing blue fluorescence) on gamma
      crystallins as compared with glucose. CONCLUSION: Human fetal gamma 1- and gamma
      3-crystallins are sensitive, at different extent (gamma 1 > gamma 3), to response
      to non-enzymatic glycation, and fructose has stronger effect than glucose on the
      glycation.

PMID- 9275745
TI  - [Reduction of induced corneal astigmatism after IOL implantation by small
      incision technique].
AB  - PURPOSE: To investigate the effect of incision length on corneal astigmatism
      after intraocular lens implantation. METHODS: The change of induced corneal
      astigmatism was observed in 36 patients underwent phacoemusification cataract
      extraction with intraocular lens implantation through a 6.5 mm limbal incision
      comparing with that in extracapsular cataract extraction with intraocular lens
      implantation through a 11 mm limbal incision. RESULTS: The surgically induced
      astigmatism in 1 week, 1.3 and 6 months after the operation was 2.13 +/- 1.41,
      1.58 +/- 1.07, 0.92 +/- 0.75 and 0.77 +/- 0.55D in 6.5 mm limbal incision group
      while that was 4.63 +/- 1.39, 3.08 +/- 1.11, 2.52 +/- 0.89 and 2.04 +/- 0.87 in
      11 mm incision group, the difference in the same postoperative period was
      significant (P < 0.05). At 1 week and 1 month postoperatively, 52.8% and 61.41%
      of 6.5 mm limbal incision cases had uncorrected visual acuity of 0.5 or better
      compared with 28.6% and 37.1% of 11 mm incision cases (P < 0.05). There was no
      difference of the uncorrected visual acuity 6 months after the surgery between
      the two groups. CONCLUSION: Reducing incision can minimize surgically induced
      astigmatism and promote early postoperative visual rehabilitation.

PMID- 9275746
TI  - [Trabeculectomy combined with extracapsular cataract extraction and posterior
      chamber intraocular lens implantation].
AB  - PURPOSE: To evaluate the effect of trabeculectomy combined with extacapsular
      cataract extraction and posterior chamber intraocular lens implantation (triple
      surgeries) on the patients of coexisting cataract and glaucoma. METHODS: 18 cases
      (19 eyes) of coexisting cataract and glaucoma treated by the triple surgeries
      were reviewed. Mean follow-up was 14.7 months (rangs from 2 to 20 months).
      RESULTS: Intraocular pressure was controlled satisfyingly in all cases except one
      case required additional treatment of the anti-glaucoma drug. 78.9% of patients
      achieved 0.3 or better visual acuity. The operation complications consist of
      anterior uveitis and hyphaema. However, all of them were controlled within 14
      days. CONCLUSION: The triple surgeries are safe and have definite effect on
      controlling the IOP and improving visual acuity.

PMID- 9275747
TI  - [Retrograde insertion of a spherical headed silicon tube through nasolacrimal
      duct].
AB  - PURPOSE: Chronic dacryocystitis or obstruction of nasolacrimal duct is one of the
      common and refractory eye diseases. The present operations have large destruction
      to lacrimal passage and unsatisfactory effects. The purpose of this research is
      to explore a simple and easy surgical method that makes small injuries and good
      curative effects. METHODS: Prob a self-made lumbar puncture needle (No. 7)
      through the lacrimal drainage system, inject fluid and put a thread into the
      inferior meatus. Guided by the thread, a special robe is retrogradely pulled
      through the nasolacrimal duct to dilate the meatus to about 3 mm. Then a silicon
      tube with a spherical head was inserted in the same may. RESULTS: 37 cases with
      chronic dacryocystitis or obstruction of nasolacrimal duct were treated by the
      method and followed up from 6 to 17 months. The result showed that the naso
      meatus was unobstructed postoperatively. The curative rate was 83.7%, which is
      better than that of other surgical methods. CONCLUSION: This operation is simple
      and painless for patients; has good curative effects and no severe complications:
      seldomly injures the normal lacrimal drainage system; can be done repeatedly or
      replaced by dacryocystorhinostomy if the procedure fails and will become the
      primarily elected method th treat the patients with chronic dacryocystitis and
      obstruction of the nasolacrimal duct.

PMID- 9275748
TI  - [777 cases of the primary conjunctival neoplasms].
AB  - PURPOSE: To make a histopathologic analysis of the primary conjuctival neoplasms.
      METHODS: The light microscopic findings of 777 cases of the primary conjunctival
      neoplasms were reported. The histochemical and immunohistochemical technologies
      were used. RESULTS: In a series of 777 primary conjunctival neoplasms, 669(86.1%)
      were benign and 108 (13.9%) were malignant. The pigmented nevi (247 cases) were
      the most common in the benign tumors, while the squamous cell carcinoma (58
      cases) were the most common tumors among the malignant ones. CONCLUSIONS: The
      biological characteristics of the benign and malignant tumors can be referred as
      differential diagnosis. There is the spindle cell and mucoepidermoid type in the
      squamous cell carcinoma of the conjunctiva. Postoperative recurrent factor of the
      malignant melanoma of the conjunctiva is numerous.

PMID- 9275749
TI  - [Clinical application of MRI in ophthalmic field].
AB  - PURPOSE: To investigate the application of MRI in ocular diseases and analysis
      the character of MRI-s parameters in these diseases. METHODS: MRI was applied
      among 68 patients with neurophthalmic disorders, orbits diseases, and intraocular
      lensions. RESULTS: The position (location) and feature of the lesions were
      diagnosed with clinical analysis. CONCLUSION: MRI possesses the special value in
      the differentiation diagnosis of neurophthalmic disease, orbit disordes and
      intraocular conditions.

PMID- 9275750
TI  - [An analysis of causes of recurrence, matastasis and death of retinoblastoma].
AB  - PURPOSE: To discuss the relationship between diagnosis, treatment and recurrence,
      metastasis, death of Rb patients. METHODS: To analyse the data of 46 Rb patients
      treated in our center from July 1967 to May 1992, who had either recurrence,
      metastasis or died. RESULTS: The main factors affecting Rb prognosis are: 1 early
      or late diagnosis: 2 the mortality rate increased with the degree of optic nerve
      involvement: 3 involvement of orbit, cranial cavity and choroid by Rb; 4
      clinically, secondary glaucoma often accompanied by optic nerve involvement.
      CONCLUSIONS: Delay in diagnosis and treatment will result in Rb recurrence,
      metastasis and death. Early diagnosis and treatment is very important for
      survival rate.

PMID- 9275751
TI  - [Retinal detachment with vitreous hemorrhage].
AB  - PURPOSE: To have the knowledge of the diagnosis in time and the choice of
      operations of retinal detachment with vitreous hemorrhage. METHODS: Sixty eight
      eyes in 68 cases of retinal detachment with vitreous hemorrhage were reviewed and
      the main factors affect the operative effect were analysed. RESULTS: Retinal
      detachment with vitreous hemorrhage usually causes PVR. The successful rate of
      the operation is low by scleral blucking procedure only, but it can be raised
      when the operation is combined with vitrectomy. CONCLUSIONS: Owing to the
      vitreous hemorrhage which has influence on the examination of fundus, it is
      difficult to make the diagnosis and treatment of retinal detachment. Furthermore,
      vitreous hemorrhage is easy to cause intraocular inflammatory reaction and PVR.
      Once the diagnosis is definite, the operation should be taken as soon as
      possible.

PMID- 9275753
TI  - [The report of orbit echinococcosis in four cases].

PMID- 9275752
TI  - [Observation of compensatory head posture in superior oblique muscle paralysis].
AB  - PURPOSE: Superior oblique muscle paralysis is the most common disease in clinic.
      We analysed the cause, machanism and regularity of compensatory head posture in
      superior oblique muscle paralysis. METHODS: All of 27 cases with superior oblique
      muscle paralysis aere examined regularly, and special muscle, binocular single
      vision function with synoptophore examined. Bielschowsky test was made. RESULTS:
      In our cases, the incidence rate of compensatory head posture was 40.7%, which
      had relations with age when a patient had disease, period and function of
      binocular single vision. CONCLUSION: The existance of binocular single vision
      function is the physiological bases leading to compensatory head posture, and the
      patients whose ages are older than 3 years and the course is less than 10 years
      may present the compensatory head posture. So we should pay attention to early
      diagnosis and training to restore the binocular single vision function.

PMID- 9275754
TI  - Urticaria. Evaluation and treatment.

PMID- 9275756
TI  - Therapeutic strategies in NIDDM an update.

PMID- 9275755
TI  - Some metabolic, humoral and genetic aspects of arterial hypertension.
AB  - Our paper is discussing the presence and intensity of metabolic, humoral and
      haemodynamic abnormalities in mild middle-aged essential hypertensives (EH) and
      in hereditary predisposed still normotensive offspring from hypertensive families
      and their possible association with candidate genes changes. Four groups of
      subjects were compared (middle-aged normotensive controls (n = 21), corresponding
      patients with EH (n = 21), normotensive offspring from hypertensive (SH) (n = 56)
      and normotensive families (SN) (n = 56). Our results demonstrate that middle-aged
      patients with EH in our country have the same indices of hyperinsulinemia,
      impared glucose tolerance and insulin-sensitivity as previously described for
      other populations. They are accompanied by higher plasma concentrations of
      vasopressor substance like catecholamines, endothelin and lower levels of
      vasodepressor substances as ANP and kallikrein. The finding of similar, but
      quantitatively less expressed metabolic and humoral changes in SH but not in SN
      support the evidence for hereditary background of these abnormalities. The
      humoral and metabolic abnormalities may participate in BP elevation and in
      morphological and functional changes of left ventricle seen in SH (higher LV mass
      index, impaired diastolic filling). We did not prove an association between BP
      and polymorphism of ACE and angiotensinogen genes, however, our findings of
      association of DD genotype for ACE and M235 for angiotensinogen with higher
      insulinemia, plasma catecholamines and plasma renin activity evoke the
      hypothesis, whether the bearers of these genotypes, exposed for long-time to the
      higher concentrations of vascoactive substances, are not the subset of hereditary
      threatened subjects in whom clinically evident EH will manifest during their
      life.

PMID- 9275757
TI  - The surfactant system of the lung modulates pathological processes.

PMID- 9275758
TI  - Advocating for effective pain management orders.

PMID- 9275759
TI  - Using transdermal medication patches.

PMID- 9275760
TI  - HIV drug dilemma--triple threat.

PMID- 9275761
TI  - Using the net to search for a job.

PMID- 9275763
TI  - Nursing on trial.

PMID- 9275762
TI  - I.v. rounds: understanding needle-free access devices.

PMID- 9275764
TI  - Medication error--nurses indicated.

PMID- 9275765
TI  - Calling all nurses--how to perform telephone triage.

PMID- 9275766
TI  - Acute asthma attack.

PMID- 9275767
TI  - Looking for hidden danger--fecal occult blood testing.

PMID- 9275768
TI  - Getting close to Rachael.

PMID- 9275769
TI  - PT and APTT--seeing beyond the numbers.

PMID- 9275770
TI  - Assessing S3 and S4 heart sounds.

PMID- 9275771
TI  - New drugs. Part III.

PMID- 9275772
TI  - Reducing cardiovascular risks.

PMID- 9275773
TI  - Amazing grace--two patients forge an unlikely bond.

PMID- 9275774
TI  - Health reform process.

PMID- 9275775
TI  - The preparation and introduction of nursing auxiliaries: the MidCentral Health
      experience.
AB  - This paper outlines how nursing auxiliaries (known as care assistants) were
      successfully introduced into MidCentral Health. The professional issues this
      introduction created are discussed, and the measures taken to maintain standards
      of care described.

PMID- 9275776
TI  - False assumptions, ethnocentrism and cultural imposition ... Madeleine
      Leininger's theory of culture care and its place in Aotearoa.

PMID- 9275777
TI  - Leininger's critique response to Coup's article on cultural safety (Ramsden) and
      culturally congruent care (Leininger) for practice.

PMID- 9275778
TI  - New Zealand military nurses fight for recognition: World War One-World War Two.
AB  - This article examines the battle undertaken by New Zealand's military nurses to
      gain recognition as officers. The fight to win this battle took from just prior
      to World War One to mid-way through World War Two-twenty seven years. Issues such
      as male domination of the military and the government, the generally accepted
      work of women in war and the lack of knowledge concerning nursing's
      professionalism combined to create a situation whereby practical recognition of
      the nurses did not take place until visual alterations were made to uniforms in
      1941.

PMID- 9275779
TI  - Her story: Phillys Streeter (nee Wright) RGN, maternity nurse. Interview by
      Lynette Low.

PMID- 9275780
TI  - Sunset over Paremoremo.

PMID- 9275781
TI  - What's happening here? Are we seeing the mindless recording of the patient's
      demise?

PMID- 9275782
TI  - This is not the future: this is the present!

PMID- 9275783
TI  - Factors that influence plastic surgeons' advice about reconstruction to women
      with breast cancer.
AB  - The purpose of this pilot study was to describe the factors that influence the
      advice of plastic surgeons who offer reconstructive surgery to women with breast
      cancer. Answers to the following question were sought: What anatomical,
      technical, and personal factors are considered by plastic surgeons in their
      recommendations for reconstruction to women with breast cancer? Five themes
      emerged that explained approaches used with these patients: (1) technical issues
      and challenges, (2) patient-centered challenges, (3) aids to patient decision
      making, (4) illusion of no loss, and (5) age.

PMID- 9275784
TI  - Perioperative management of the pediatric patient.
AB  - Children are not just small adults. Perioperative nurses working with pediatric
      patients plan nursing interventions based on established principles of
      perioperative practice as well as incorporating concepts of growth and
      development relating to the child. A thorough assessment of the pediatric patient
      prior to surgery enables the perioperative nurse to plan for the surgical
      procedure, modifying as need be for the individual patient's specific needs. With
      adequate preparation, communication, and emotional support, the pediatric
      surgical experience can be positive for the child, parents, and perioperative
      team.

PMID- 9275785
TI  - The inspection.

PMID- 9275786
TI  - Nerve injuries following TRAM flap surgery.
AB  - The purpose of this study was to determine whether nerve injuries related to
      patient positioning could be prevented in patients undergoing transverse rectus
      abdominous myocutaneous (TRAM) flap breast reconstruction surgery. Gel pads were
      used on the arms, and the patient's arms were secured along the full length of
      the armboard. Ninety-one patients have undergone TRAM without any nerve injury.
      We conclude that use of pads and full length boards had reduced the risk of
      intraoperative positional nerve injury.

PMID- 9275787
TI  - Employee performance reviews: a necessary "evil"?

PMID- 9275788
TI  - Measurement of body temperature in pediatric patients.

PMID- 9275789
TI  - Aesthetic plastic surgery for teenagers: when is it appropriate?

PMID- 9275790
TI  - Members express pride and expectations of society.

PMID- 9275791
TI  - Outcomes research: are we rigorous enough?

PMID- 9275792
TI  - Alzheimer's disease: where small victories create large hopes.

PMID- 9275793
TI  - Cancer and hunger: renewing health, morale.

PMID- 9275794
TI  - Menopause, science and culture.

PMID- 9275795
TI  - Surgery: protecting the lungs.

PMID- 9275796
TI  - HIV and AIDS: time to live.

PMID- 9275797
TI  - Heart surgery: lifestyle impacts recovery.

PMID- 9275798
TI  - Work place safety for nurses: reality vs. perception.

PMID- 9275799
TI  - Hopeful teenagers with cancer: living courage.

PMID- 9275800
TI  - Gender differences. Exercise beliefs among youth.

PMID- 9275801
TI  - Building an exercise identity.

PMID- 9275802
TI  - What causes stress in mothers of chronically ill children?

PMID- 9275803
TI  - Health workers are key to fire prevention.

PMID- 9275804
TI  - Nursing education: a quest to apply research.

PMID- 9275805
TI  - Nursing education: urban university inspires service to under served.

PMID- 9275806
TI  - Growth and development of a cardiac rehabilitation support group.
AB  - This article describes the initiation and evolution of the support group
      component of a cardiac rehabilitation pilot program. It also outlines how the
      group was initiated and discusses the group's development during the 20 weeks of
      its existence. The description of this nurse-facilitated support group provides a
      model for clinicians interested in integrating such an approach into their own
      cardiac rehabilitation programs.

PMID- 9275807
TI  - Using a 6-minute walk test to predict outcomes in patients with left ventricular
      dysfunction.
AB  - Maximal oxygen consumption (VO2MAX) is an independent variable that predicts
      outcomes in patients suffering from left ventricular dysfunction (LVD).
      Determining VO2MAX in a rehabilitation setting is not only costly and time
      consuming but it would also be beyond many patients' physical abilities. This
      study's goal was to show that a simpler and less costly 6-minute walk test can
      predict mortality in patients with LVD. Sixty-six Phase 1 cardiac rehabilitation
      patients with LVD performed the 6-minute walk test upon admission and at
      discharge from a rehabilitation hospital. Upon discharge, the group that was able
      to walk significantly longer distances upon discharge had a higher survival rate
      3 months after discharge. The 6-minute walk test can predict longer survival in
      patients with LVD and can provide valuable information for determining treatment
      plans, future prognosis, and home disposition of deconditioned LVD patients in a
      rehabilitation setting.

PMID- 9275808
TI  - Quality of life and coping strategies of clients with COPD.
AB  - A descriptive correlational design was used to study quality of life and coping
      in 39 clients with severe chronic obstructive pulmonary disease (COPD). Quality
      of life was measured by using the Sickness Impact Profile (SIP) and Cantril's
      Ladder; coping strategies were measured with Jalowiec's Coping Scale Revised
      (JCS). SIP and Cantril's Ladder scores revealed that the subjects experienced a
      high quality of life. Total coping scores were low, however, implying that
      patients used the JCS coping strategies only minimally and did not find them
      particularly helpful. A moderately strong relationship was found between the
      objective and subjective measures of quality of life. Coping strategies and
      quality of life were found not to be significantly related. Findings suggest that
      the caregivers of those with severe COPD should consider the client's perception
      of quality of life and use of coping strategies. Further research is needed to
      determine the factors that affect quality of life for these persons.

PMID- 9275809
TI  - The FAMTOOL family health assessment tool.
AB  - The purpose of this study was to design and validate a family health assessment
      tool (FAMTOOL) based on a concept analysis of family and health. Preliminary
      testing of this instrument by a convenience sample of 80 adults resulted in an
      internal consistency coefficient of .90. A retest 2 weeks later produced a
      stability coefficient of .96. The FAMTOOL provides rehabilitation nurses with a
      quick, positive assessment instrument for helping patients and their family
      members assess their own family's health, compare responses with each other, and
      see strengths they might not have considered otherwise. As the family health
      system should be included in the initial assessment of everyone entering the
      healthcare system, the FAMTOOL may prove helpful to nurses in a wide variety of
      primary, secondary, and tertiary settings.

PMID- 9275810
TI  - The pathophysiology of osteoporotic vertebral fractures.
AB  - Osteoporosis is an increasingly prevalent chronic metabolic bone disease,
      characterized by low bone mass that subsequently leads to bone fractures.
      Vertebral fractures are the most common and the most debilitating of osteoporotic
      fractures. People with osteoporotic vertebral fractures present a unique
      challenge to rehabilitation nurses. A better understanding of the complex
      pathophysiological processes that contribute to this disability will help nurses
      provide more comprehensive care and education to this growing segment of the
      population. This article presents an overview of normal physiology and a
      discussion of the pathophysiological changes that occur in the skeletal,
      endocrine, and neurological systems throughout the development of osteoporotic
      vertebral fractures.

PMID- 9275811
TI  - Transitions in chronic illness: rheumatoid arthritis in women.
AB  - This article describes transition theory as it relates to a qualitative study of
      women with rheumatoid arthritis (RA) and the importance of this theory in nursing
      practice. Rheumatoid arthritis is prototypical of many chronic illnesses because
      it has a profound impact on activities of daily living. It frequently occurs
      during a person's most productive years and continues throughout life. Because a
      person with RA typically experiences a number of exacerbations and remissions
      over the course of many years, transition theory was chosen as a framework for
      this study. The study sample consisted of 30 women with RA, who were interviewed
      about their experiences of living with this chronic illness. The women described
      four distinct phases in learning to live with RA, which began with awareness and
      proceeded to mastery. These findings are consistent with the stages of transition
      described by other investigators.

PMID- 9275812
TI  - The nuts and bolts of pacemakers: what nurses need to know.

PMID- 9275813
TI  - Participating in health fairs: opportunities for rehabilitation nurses and people
      with brain injury.

PMID- 9275815
TI  - The case study as a research strategy.
AB  - A research strategy seldom used in the caring sciences is the case study. A case
      study is an empirical in-depth inquiry about an individual, family, group or
      organization. It is preferable when 'how' and 'why' questions are asked. The case
      study is mainly used to explain those causal links in real-life intervention that
      are too complex for either the survey or experimental strategies. Like other
      research strategies, its design includes questions or propositions, units of
      analysis, the logic linking the data to the questions or propositions, and the
      interpretations of the outcomes. A case study can be reported as a single case or
      as a compilation of a series of cases. In conclusion, a case study is a simple
      and excellent way for a care professional to present him or herself to the
      scientific world.

PMID- 9275816
TI  - Elderly persons' social network and need for social support after their first
      myocardial infarction.
AB  - Social network and social support are phenomena suggested to be of importance to
      successful recovery from myocardial infarction. However, very few studies have
      been carried out, especially among the elderly, focusing on their social network
      and its ability to provide adequate support after myocardial infarction. The aim
      of this study was to examine elderly persons' social network and need for social
      support three months after their first myocardial infarction. The sample
      consisted of 128 persons between 65 and 94 years of age who answered a
      questionnaire. The results showed that the subjects, even the oldest ones, had an
      available social network and that they were satisfied with the support it
      provided. There was an increased need for social support after the myocardial
      infarction, especially for emotional support and appraisal, but also for
      instrumental aid and information. Despite these positive results indicating that
      elderly persons with myocardial infarction have a social network, whose members
      provide them with support, there may be a need for support also from persons
      outside this network. Assessment of social network characteristics and the need
      for social support as well as the provision of adequate information about
      additional support networks are important tasks for all health professionals.

PMID- 9275817
TI  - Cognitive processes nurses and doctors use in the administration of PRN (at need)
      analgesic drugs.
AB  - The report is a descriptive, comparative study of the cognitive processes used by
      doctors and nurses when deciding whether or not to administer prn drugs to
      postoperative cancer patients. Simulations, together with the think aloud
      technique to provide verbal protocols was the method chosen. The theoretical
      framework chosen for the analysis was the information processing theory. Five
      doctors and 5 nurses, each with at least 5 years of working experience were
      interviewed. The interviews were transcribed so that a content analysis could be
      performed. The main findings were the following: doctors and nurses generated
      hypotheses early in the interview; the only statistically significant difference
      between the two groups was the wider use of theory and/or experience as a source
      of information by doctors. Although differences are not statistically
      significant, nurses appear to collect more information on and from the patient
      and more information on vital signs and symptoms other than pain than the
      doctors. Differences derived from analysis of the statements expressed by the
      subjects suggested that nurses pay more attention to the patient's psychological
      problems and that, while doctors' main concern was to make the right diagnosis,
      the nurses' main concern were patients' reactions and collaboration.

PMID- 9275818
TI  - Assessing the need for challenging behaviour services in an English health
      district.
AB  - The aim of the present study was to assess the health care needs for people with
      learning difficulties who display challenging behaviour in a newly established
      health district. Ninety-eight clients were studied, using Disability Assessment
      Schedule (DAS), Aberrant Behaviour Checklist (ABC) and The Psychopathology
      Inventory for Mentally Retarded Adults (PIMRA). The results showed that a large
      proportion of them were mobile, continent and able to feed themselves. Almost
      half had no problems in communication but less than half were sociable. On the
      whole, they did not have adequate skills. A large proportion of them did not
      present severe challenging behaviour and did not suffer from psychiatric
      illnesses, apart from inappropriate adjustment disorder. Correlation coefficients
      showed that there were relationships between challenging behaviours and some of
      clients' disabilities and inappropriate adjustment disorder.

PMID- 9275819
TI  - Needs as expressed by women after breast cancer surgery in the setting of a short
      hospital stay.
AB  - The aim of this study was to describe needs as expressed by a group of women
      after surgery for breast cancer in the setting of a short hospital stay. Ten days
      after surgery, 97 women answered an open-ended question about their perception of
      the care given. A content analysis inspired by the method of Grounded Theory was
      used. Satisfaction with the personal treatment and feelings of abandonment were
      identified as the two main themes. Expressed needs (n = 113) were classified in
      five categories: Trust, Information, Practical Assistance, Personal Treatment and
      Emotional Support, of which Trust appeared to be the core concept. In addition,
      time and space emerged as two dimensions that were interwoven with the categories
      of needs. The patients' perception of trust in the staff was interpreted as
      depending on whether the needs in the other categories were satisfied or not. It
      is hypothesized that, to fulfil the patients' need of trust, the patients have to
      be satisfied at least with information, practical assistance, personal treatment
      and emotional support. We consider that, in an organization with a high degree of
      continuity, when the patients are aware of the physician and nurse responsible,
      the possibilities for trust are increased, especially in short hospital stays.

PMID- 9275820
TI  - Reliability and validity of the Norwegian version of the Nowotny Hope Scale. A
      nursing tool for measuring hope in cancer patients.
AB  - The purpose of the present study was to assess the reliability and validity of
      the Norwegian version of the Nowotny Hope Scale as applied to cancer patients.
      The questionnaire was first translated into Norwegian following internationally
      accepted guidelines. The scale was tested on a sample consisting of 131 newly
      diagnosed cancer patients. The findings supported the internal consistency of the
      instrument as a whole (alpha = 0.89) and of the six subscales: confidence (alpha
      = 0.85), relates to others (alpha = 0.75), future is possible (alpha = 0.80),
      spiritual beliefs (alpha = 0.94), active involvement (alpha = 0.53) and comes
      from within (alpha = 0.80). Stability over time was provided by a satisfactory 3
      4-week test-retest correlation (r = 0.81). The validity was confirmed by the
      judgement of an expert and by a principal components analysis with orthogonal
      rotation. The result of the factor analysis was somewhat different from the
      original findings in an American sample. The results obtained in this study are
      promising and indicate that the Nowotny Hope Scale can be used to measure hope in
      newly diagnosed Norwegian cancer patients.

PMID- 9275821
TI  - Patterns of care for patients with cancer before and after the establishment of a
      hospice ward.
AB  - A majority of people die in acute hospital care, in a culture of quickness
      primary aimed at curing. There are indications that hospice care in various forms
      will spread during the present decade in Sweden. The hospice philosophy
      contributes to a culture of slowness, where the patient is not only allowed but
      is encouraged to live at his own pace. As a first step in establishing for whom
      hospice inpatient care is the best alternative, patient flow to a newly started
      hospice ward was studied. All patients (n = 1464) who died at the Medical Centre
      Hospital with a primary diagnosis of cancer during the period of study were
      compared regarding place of death, diagnosis, gender, age and length of the last
      period of care. The year before the ward was established, 82% of patients died in
      acute hospital care compared with 59% during the hospice ward's third year of
      operation. A total of 315 patients (22%) died in the hospice ward during the
      study period. The percentage of these patients over the age of 80 was
      significantly higher (p = 0.0001), and they also had a longer continuous final
      period of care. More women (57%) than men (43%) were cared for at the hospice
      ward. The hospice ward has in this way influenced the pattern of care in the
      hospital.

PMID- 9275822
TI  - The perception of aggression.
AB  - Several academic and clinical disciplines are involved in clarifying the concept
      of aggression by formulating operational and descriptive definitions. In the
      present paper the validity of the definitions of aggression, reported by nurses
      in an earlier qualitative study, is examined, using a survey approach among
      nurses of five general psychiatric hospitals in the Netherlands. Three dimensions
      of aggression were found; aggression as a normal, adaptive reaction, aggression
      as a violent reaction and aggression as a functional reaction. These findings
      match the results of the qualitative study. It was investigated whether there was
      a relation between personal and environmental characteristics of the nurses and
      the way they perceive aggression. The gender of the respondents, the setting in
      which they were working, the degree to which they used constraint measures and
      whether patients were voluntarily admitted or not, were related to the perception
      of aggression. The study points out that different instruments are needed to
      measure the prevalence or incidence of aggression and to diagnose or to intervene
      on aggression in clinical practice.

PMID- 9275824
TI  - [Nursing personnel and professional risk].

PMID- 9275823
TI  - The effectiveness of the mental health nursing interventions in a general
      hospital.
AB  - The purpose of the study was to investigate: a) how mental health nursing
      interventions were provided to general hospital patients, who during their
      hospitalization presented psychological/pyschiatric problems and b) how the
      patients actually evaluate the effectiveness of the care given to them. We
      interviewed 95 medical-surgical patients, who were referred to the psychiatric
      consultation-liaison service of a general hospital. During the interview, a
      nursing evaluation of the patients' psychological problems took place, followed
      by appropriate mental health nursing interventions which were taken from the
      NOSIE scale and the standards of the Psychiatric Mental Health Nursing Practice.
      Anxiety was the most common problem 41.1% in the referrals. The comparison of the
      mean value of the patients' problems before and those after the mental health
      nursing interventions, showed statistically significant reduction of the
      problems. Also, the comparison of the mean value in the fourth assessment of the
      patients' problems with the mean value of the patients' opinion, showed an
      achievement in facilitating the verbal expression and comforting the physical and
      psychological symptoms to a point statistically significant.

PMID- 9275825
TI  - [Backache: prevention and limits].

PMID- 9275826
TI  - [Psychological malaise and the risk of burnout in nurses].

PMID- 9275827
TI  - [Prevention of burnout and ergonomics].

PMID- 9275828
TI  - [The professional and AIDS].

PMID- 9275829
TI  - [Hospitalization at home--home care. Evaluating the importance of the home in
      tomorrow's health care].

PMID- 9275830
TI  - [Latex allergy; a major public health problem].

PMID- 9275831
TI  - [The risk of occupational tuberculosis contamination].

PMID- 9275832
TI  - [Professional chemical dermatoses in the medical field].

PMID- 9275833
TI  - [Deep venous thrombosis].

PMID- 9275834
TI  - [Expertise; a theoretical reference].

PMID- 9275836
TI  - [Nursing expertise and daily reality].

PMID- 9275835
TI  - [Did you say expertise? Let us talk about it].

PMID- 9275837
TI  - [Professional training between practice and expertise].

PMID- 9275839
TI  - [Expertise. Between events and equipment].

PMID- 9275838
TI  - [Becoming an expert from one's apprenticeships. Developing cognitive
      imagination].

PMID- 9275840
TI  - [Let the students speak out. Introduction of a period of psychoanalysis during
      training].

PMID- 9275841
TI  - [Ethics in nursing].

PMID- 9275842
TI  - [Letter to a nurse manager who wants to change...].

PMID- 9275844
TI  - [I was a happy little girl].

PMID- 9275845
TI  - [Renunciation of life. Suicides and attempts].

PMID- 9275846
TI  - [Malaise in the aged].

PMID- 9275847
TI  - [Knowing more in order to help. Percutaneous endoscopic gastrostomy].

PMID- 9275849
TI  - [Home care and abusive institutionalization].

PMID- 9275848
TI  - [Nutrition and aging].

PMID- 9275850
TI  - [Balneotherapy in retirement homes].

PMID- 9275852
TI  - [Obligation to feed. Contribution by the family to the cost of hospitalization or
      accommodations of their elders].

PMID- 9275851
TI  - [Better living. The walkers. Help in walking].

PMID- 9275853
TI  - [Architecture. The Studio. The concept of the Arpage residences].

PMID- 9275854
TI  - [Ordinary violence].

PMID- 9275855
TI  - [Everyday life and the meals].

PMID- 9275856
TI  - [The elderly and emergencies. Accidents with anticoagulants].

PMID- 9275857
TI  - [Dietetics. Nutritional input].

PMID- 9275858
TI  - [Sleep and the elderly].

PMID- 9275859
TI  - [Preventing nurses' exhaustion].

PMID- 9275860
TI  - [Comfort and quality of care. Hydrating a dependent patient. Understanding the
      mechanism of deglutition].

PMID- 9275861
TI  - [Problems and behaviors. The problem of geriatric wandering].

PMID- 9275862
TI  - [Practical help. Tele-assistance].

PMID- 9275863
TI  - [ The physical therapist and guidance].

PMID- 9275864
TI  - On winemaking and radiology.

PMID- 9275865
TI  - Vicarious liability.

PMID- 9275866
TI  - Assessment of the recent consensus development panel on screening women aged 40
      49 for breast cancer.

PMID- 9275867
TI  - A remote conference system for image diagnosis on the World-Wide Web.
AB  - OBJECTIVE: The World-Wide Web on the Internet enables an exchange of multimedia
      information among remote desktop computers. Therefore, a teleradiology system
      using the Web would allow remote consultation with expert radiologists. Our
      objective was to establish a Web-based prototype system for image interpretation.
      CONCLUSION: Our system allows a physician to transmit clinically useful images to
      an expert radiologist at a different location, who can see them on a Web browser
      and discuss diagnoses with the physician.

PMID- 9275868
TI  - An interactive computer-based tool for teaching the segmental anatomy of the
      liver: usefulness in the education of residents and fellows.
AB  - OBJECTIVE: The purpose of this study was to develop an interactive computer-based
      tool for teaching hepatic segment anatomy and to evaluate its usefulness for
      radiology education. CONCLUSION: An interactive computer-based teaching tool has
      been developed that effectively teaches the segmental anatomy of the liver to
      radiology residents and fellows who have a wide range of baseline knowledge of
      hepatic anatomy.

PMID- 9275869
TI  - Radiology of obstructive pulmonary disease.
AB  - Obstructive lung diseases may be associated with a variety of pathologic
      findings, including emphysema, large airways abnormalities, and small airways
      abnormalities. The usefulness of plain radiographs for showing these findings is
      limited, although the presence of obstructive lung disease can often be inferred
      in the presence of increased lung volumes, gross lung destruction (emphysema) or
      large airways abnormalities. Furthermore, radiographs may not provide useful
      information in many patients with a known disease who experience an exacerbation
      of their symptoms. Nonetheless, chest radiographs are commonly obtained in this
      setting to assess the presence or absence of disease complications. HRCT can
      reveal morphologic abnormalities associated with obstructive lung disease with a
      greater accuracy than plain radiographs. HRCT is more sensitive than radiographs
      in showing emphysema, large airways abnormalities such as bronchiectasis, and
      small airways abnormalities such as bronchiolectasis and the tree-in-bud
      appearance. Furthermore, findings associated with abnormal ventilation, including
      mosaic perfusion, can also be seen on HRCT, as can findings of air trapping on
      expiratory scans. These latter findings are particularly helpful in diagnosing
      obstructive disease in the absence of other morphologic abnormalities. Although
      the indications for use of HRCT vary with the specific disease, HRCT can be
      valuable in patients in whom the diagnosis is, on the basis of clinical and plain
      radiographic findings, in question or for whom specific therapy is being
      contemplated.

PMID- 9275870
TI  - Tuberculosis of the central airways: CT findings of active and fibrotic disease.
AB  - OBJECTIVE: Management of patients with central airways tuberculosis differs
      according to the activity of the disease. The purpose of this study was to
      analyze CT findings of active and fibrotic disease in patients with central
      airways tuberculosis. MATERIALS AND METHODS: According to bronchoscopic findings
      and biopsy results, 41 patients with tuberculosis of the trachea and main bronchi
      were categorized as having active disease (n = 30) or fibrotic disease (n = 11).
      Follow-up CT scans were obtained after antituberculous therapy in 11 patients
      with active disease and two patients with fibrotic disease. All CT scans were
      retrospectively analyzed with particular attention to the locations of airway
      lesions, patterns of luminal narrowing, wall thickening of diseased airways, and
      presence of abnormal adjacent lymph nodes. RESULTS: Active disease in 30 patients
      involved the trachea (n = 20), the right main bronchus (n = 14), or the left main
      bronchus (n = 13). Seventeen patients had multiple lesions. On CT scans, these
      airways showed irregular (n = 24) or smooth (n = 4) narrowing in 28 patients:
      minimal (n = 5) or marked (n = 18) wall thickening with contrast enhancement in
      23 patients: and obstruction with peribronchial cuffing in nine patients.
      Enlarged mediastinal lymph nodes were seen in 26 patients. Fibrotic disease in 11
      patients involved the trachea (n = 6), the right main bronchus (n = 2), or the
      left main bronchus (n = 9). Six patients had multiple lesions. On CT scans, the
      airways showed smooth (n = 7) or irregular (n = 2) narrowing without (n = 5) or
      with minimal (n = 4) wall thickening in nine patients and obstruction without
      peribronchial cuffing in four patients. On follow-up CT scans, the findings for
      the airway lesions were almost normal in nine patients who had had initial active
      disease. However, the findings for airway narrowing did not change in two
      patients with fibrotic disease after 6 months of follow-up. CONCLUSION: Principal
      CT findings in our patients depended on disease stage. Central airways narrowing
      was seen in both active and fibrotic stages. However, in patients with active
      disease, CT scans showed irregular and thick-walled airways, a pattern that was
      reversible, whereas patients with fibrotic disease generally had smooth narrowing
      of airways and minimal wall thickening, a pattern that was not reversible during
      the follow-up period.

PMID- 9275872
TI  - A mediastinal hematoma after a fall.

PMID- 9275871
TI  - Primary Sjogren's syndrome and associated lung disease: CT findings in 50
      patients.
AB  - OBJECTIVE: We prospectively evaluated the high-resolution CT findings in 50
      nonsmoking patients with proven primary Sjogren's syndrome. CONCLUSION: High
      resolution CT is a sensitive technique in assessing pulmonary involvement in
      patients with primary Sjogren's syndrome. Interstitial lung disease and
      bronchiolar inflammatory changes are common abnormal findings seen on CT scans in
      primary Sjogren's syndrome.

PMID- 9275873
TI  - Routine addition of an automated biopsy device to fine-needle aspiration of the
      lung: a prospective assessment.
AB  - OBJECTIVE: The purpose of this study was to prospectively assess the usefulness
      of the routine addition of an automated biopsy device (ABD) to fine-needle
      aspiration (FNA) of the lung and to examine the complication rate of this
      procedure. SUBJECTS AND METHODS: Fifty biopsies were performed under CT guidance
      using a coaxial technique with a 19-gauge introducer needle and a 22-gauge
      aspirating needle followed by a 20-gauge ABD. An average of 3.5 FNA specimens and
      2.5 core specimens were obtained. Cytology and histology specimens were
      interpreted separately by two experienced pathologists who were unaware of the
      other's interpretation. Final diagnoses were based on surgery, microbiology,
      definitive biopsy diagnosis, and clinical follow-up. All complications were
      recorded. RESULTS: Of 34 malignant lesions, we achieved a diagnostic accuracy of
      94% for FNA and 59% for core biopsy (p < .01). Combined accuracy was 94%. Of 16
      benign lesions, an accurate definitive diagnosis was made in 31% of cases using
      FNA and in 69% of cases using core biopsy (p = .08). Combined accuracy was 69%.
      In the subset of benign lesions that were not acute infections (n = 8), an
      accurate definitive benign diagnosis was made in 12% of cases using FNA and in
      75% of cases using core biopsy (p < .05). No false-positive diagnoses of
      malignancy occurred. Complications included pneumothorax, nine (18%) of 50 cases;
      chest tube, one (2%) of 50 cases minor pulmonary hemorrhage, seven (14%) of 50
      cases; and minor hemoptysis, two (4%) of 50 cases. CONCLUSION: The complication
      rates of FNA with the addition of an ABD are similar to those reported in the
      literature for FNA alone. The addition of an ABD significantly increases the
      diagnostic accuracy only for the subset of benign lesions that are not acute
      infections.

PMID- 9275874
TI  - The impact of routine CT of the chest on the diagnosis and management of newly
      diagnosed squamous cell carcinoma of the head and neck.
AB  - OBJECTIVE: The purpose of the study was to ascertain how often additional
      malignant neoplasms are detected on CT scans of the thorax in patients with newly
      diagnosed squamous cell carcinoma of the head and neck and to determine how often
      these findings are evident on conventional radiographs of the chest. SUBJECTS AND
      METHODS: One hundred eighty-nine patients with newly diagnosed squamous cell
      carcinoma of the head and neck were prospectively examined in a 5-year period. At
      the time of the initial diagnosis, each patient underwent both chest radiography
      (posteroanterior and lateral radiographs in 95%, anteroposterior in 5%) and
      thoracic CT to assess the prevalence of additional primary or metastatic
      malignant neoplasms of the thorax and upper abdomen. RESULTS: Of the 189 patients
      studied, 66 showed a total of 73 significant abnormalities on thoracic CT scans
      of which only 17 abnormalities (23%) were detected on chest radiographs alone. Of
      these 66 patients, 36 (55%) were found to have one or more primary or metastatic
      neoplasms. These 36 patients manifested a total of 41 additional primary or
      secondary malignant neoplasms including 24 cases in which one or more pulmonary
      nodules were detected, six cases of lymphadenopathy, three hepatic lesions, three
      bone lesions, two pleural masses, two esophageal masses and one adrenal mass. Of
      these 41 malignant tumors, 13 (32%) were synchronous primary tumors and 28 were
      metastases. Only 12 (29%) of the 41 malignant tumors detected by thoracic CT were
      seen on the chest radiographs. In all patients in which an additional malignant
      tumor was diagnosed, clinical management was significantly affected, resulting in
      a modification of the planned surgery or the addition of chemotherapy, radiation
      therapy, or both. CONCLUSION: A relatively large percentage of patients (19%)
      with newly diagnosed squamous cell cancer of the head and neck was found to have
      additional malignant tumors, 32% of which were synchronous primary tumors. The
      discovery of these additional neoplasms had a major effect on both the therapy
      and the prognosis of these patients. The combination of a relatively poor
      detection rate for conventional chest radiography, with only 29% of the malignant
      tumors detected on CT scans of the chest being seen on chest radiographs, and the
      high prevalence of disease in this population support the routine inclusion of
      thoracic CT in these patients.

PMID- 9275875
TI  - Bronchiolitis obliterans after lung transplantation: high-resolution CT findings
      in 15 patients.
AB  - OBJECTIVE: The purpose of this study was to compare the high-resolution CT
      findings in patients with pathologically proven bronchiolitis obliterans after
      lung transplantation with high-resolution CT findings in control subjects.
      MATERIALS AND METHODS: High-resolution CT examinations of 15 patients with
      pathologically proven bronchiolitis obliterans after lung transplantation and 18
      control subjects were retrospectively evaluated by two independent observers who
      were unaware of the diagnosis in each case. All 33 subjects underwent inspiratory
      high-resolution CT. Five patients with bronchiolitis obliterans and 16 control
      subjects underwent expiratory CT. RESULTS: Findings in patients with
      bronchiolitis obliterans included bronchial dilatation in 80%, mosaic perfusion
      in 40%, bronchial wall thickening in 27%, and air trapping in 80%, compared with
      the control subjects with bronchial dilatation in 22%, mosaic perfusion in 22%,
      and air trapping in 6%. The combination of bronchial dilatation on the
      inspiratory CT scan and air trapping on the expiratory CT scan was seen only in
      patients with bronchiolitis obliterans. We calculated good agreement between the
      two observers (kappa > or = .63). CONCLUSION: Air trapping and bronchial
      dilatation were the two most sensitive and specific findings on high-resolution
      CT scans of patients with bronchiolitis obliterans. The combination of these two
      findings was seen exclusively in patients with bronchiolitis obliterans.

PMID- 9275876
TI  - Pulmonary sequestration spectrum: a new spin with helical CT.

PMID- 9275877
TI  - Localized benign fibrous tumors of the pleura.

PMID- 9275878
TI  - Displaced extrapleural fat as revealed by CT scanning: evidence of extrapleural
      hematoma.

PMID- 9275879
TI  - Pulmonary carcinosarcoma: radiologic and pathologic findings in three patients.
AB  - OBJECTIVE: The purpose of this study was to describe the radiologic and
      pathologic features of pulmonary carcinosarcoma in three patients. CONCLUSION:
      The tumors measured 9-14 cm in diameter, had inhomogeneous contrast enhancement,
      and in two cases had invaded the mediastinum or chest wall extensively.
      Carcinosarcomas are rare tumors that tend to be large, necrotic, enhancing, and
      locally invasive.

PMID- 9275880
TI  - Retropharyngeal parathyroid adenoma: precise preoperative localization with CT
      and arterial infusion of contrast material.

PMID- 9275882
TI  - Preliminary experience with power Doppler imaging of solid breast masses.
AB  - OBJECTIVE: The purpose of our study was to assess the potential of power Doppler
      imaging (PDI) to differentiate benign from malignant solid breast masses.
      MATERIALS AND METHODS: Sixty-nine biopsy-proven solid breast masses were
      evaluated with PDI using 7- to 10-MHz transducers optimized for low-volume flow
      sensitivity. The extent of flow on PDI was estimated as a percentage of the
      lesion area on multiple longitudinal and transverse static sonographic images.
      Flow was categorized as avascular; less than 10%; 10-25%; 25.1-50%; and greater
      than 50%. RESULTS: Of the 69 lesions evaluated, 33 were malignant and 36 were
      benign. Of the avascular lesions, nine were malignant and eight were benign.
      Significant overlap was seen in the vascularity of the other 52 lesions: both
      malignant and benign lesions revealed a similar range of vascular patterns.
      CONCLUSION: Preliminary experience with PDI suggests that both malignant and
      benign lesions can be avascular and that the presence of color within a solid
      breast mass is a nonspecific finding. Assessing the extent of vascularity with
      PDI appears to be of limited value in the diagnostic evaluation of solid breast
      masses.

PMID- 9275881
TI  - Use of breast core biopsy in the United States: results of a national survey.
AB  - OBJECTIVE: We analyzed the results of a national survey to determine the current
      use and practice of breast core biopsy. MATERIALS AND METHODS: A survey was
      mailed to 1700 members of the Society of Breast Imaging who reside in the United
      States. The questions included frequency of biopsy, specialty of responsible
      physician, type of guidance used, physician credentialing, method and duration of
      follow-up, referral patterns, scheduling practices, and types of lesions
      biopsied. Opinions about the future usefulness of breast core biopsy were
      solicited. RESULTS: We received 458 responses (27% response rate) from 48 states
      and the District of Columbia. Eighty-one percent of the respondents indicated
      that breast core biopsy is performed at their practice or institution: among
      these, 85% are performed solely by radiologists. Of those performing the
      procedure, 61% do not have special credentials. Seventy-one percent use both
      stereotaxic and sonographic guidance. For follow-up after the procedure, patients
      are tracked manually and by computer in near-equal proportions. The median period
      of patient follow-up is 12 months: 11% of the respondents track indefinitely.
      Surgeons and primary care physicians most commonly refer patients for core
      biopsy. The procedure is most often performed after notification of the referring
      physician (76%), and 80% of the respondents schedule core biopsy without prior
      surgical consultation. Masses and calcifications categorized as probably benign
      to highly suspicious are included as indications for core biopsy. Forty percent
      of the respondents offer core biopsy on the same visit as when an abnormality is
      found. Eighty percent of the respondents believe the procedure will increase in
      use 48% believe that core biopsy will replace most surgical biopsies for
      nonpalpable lesions. CONCLUSIONS: Breast core biopsy is widely used in the United
      States for sampling a broad spectrum of imaging abnormalities. Both sonographic
      and stereotaxic guidance are commonly used. Credentialing requirements, practice
      patterns, and follow-up after the core biopsy procedure vary considerably among
      different sites.

PMID- 9275883
TI  - Metaplastic carcinoma of the breast: mammographic appearance with pathologic
      correlation.
AB  - OBJECTIVE: The objective of this study was to describe the mammographic
      appearance with pathologic correlation of metaplastic carcinoma of the breast.
      CONCLUSION: Metaplastic carcinomas of the breast are masses with mammographic
      characteristics of low suspicion because of their histologic appearance.
      Metaplastic carcinoma should be included in the differential assessment of
      predominately circumscribed, noncalcified masses revealed on mammography. One
      salient feature that may distinguish metaplastic carcinomas is the occurrence of
      a circumscribed portion with a spiculated portion, which is seen in carcinomas
      that have a significant mixture of metaplastic and invasive carcinoma growth
      patterns.

PMID- 9275884
TI  - Mammography of breasts in which catheter cuffs have been retained: normal,
      infected, and postoperative appearances.
AB  - OBJECTIVE: The purpose of this report is to show that Dacron (DuPont, Wilmington,
      DE) cuffs retained in breasts after the removal of Hickman catheters may result
      in complications requiring radiographic evaluation for subsequent management. We
      also describe potential complications, including infection, associated with a
      retained cuff and changes after the removal of a retained cuff. CONCLUSION:
      Because of the increased use of Hickman catheters for central vein access, Dacron
      cuffs more frequently are retained in breasts and are likely to be seen on
      mammograms. Radiologists need to be aware of the mammographic findings of a
      normal cuff, infected cuff, and the site of a surgically excised cuff.

PMID- 9275885
TI  - Thrombolysis of infrapopliteal bypass grafts: efficacy and underlying
      angiographic pathology.
AB  - OBJECTIVE: The purpose of this study was to determine retrospectively the
      effectiveness of thrombolysis of occluded infrapopliteal bypass grafts and to
      identify factors affecting success. MATERIALS AND METHODS: The records of 52
      consecutive patients (52 grafts) who underwent selective urokinase thrombolysis
      of grafts to the pedal or tibial arteries were reviewed. The need for subsequent
      surgery and the influence of diabetes on outcome were analyzed. RESULTS: There
      were 43 vein and nine Goretex (W-L Gore, Flagstaff, AZ) and vein composite grafts
      inserting into tibial and peroneal arteries (n = 28) or pedal arteries (n = 24).
      Mean time of follow-up was 19 months. All grafts were entered, and technical
      success was achieved in 73% of patients. Twenty-six patients required some form
      of graft revision. Overall patency at 30 days was 76%. Thirty-day limb-salvage
      and mortality rates were 82% and 4%, respectively. No significant difference was
      found in 1-yr outcomes between diabetic and nondiabetic patients or between pedal
      and tibial grafts. Major complications occurred in eight patients (15%).
      CONCLUSION: Thrombolysis of occluded grafts that insert into the pedal or tibial
      vessels was as effective as thrombolysis of more proximal grafts and native
      arterial thrombolysis, which have reported 30-day limb-salvage rates that range
      between 80% and 90%. Diabetes and grafting to foot vessels did not adversely
      affect response to thrombolysis. Surgery was often required to correct an
      underlying lesion revealed by thrombolysis. Despite the small size of the
      arteries to which the grafts were anastomosed, selective thrombolysis of occluded
      infrapopliteal bypass grafts proved to be an effective procedure.

PMID- 9275886
TI  - Symptomatic hemangiomas and venous malformations in infants, children, and young
      adults: treatment with percutaneous injection of sodium tetradecyl sulfate.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of
      percutaneous sclerosis therapy using sodium tetradecyl sulfate for treatment of
      symptomatic hemangiomas and venous malformations in infants, children, and young
      adults. MATERIALS AND METHODS: Fifty-two sclerosis procedures were performed in
      21 patients who were 13 months to 24 years old. Six of these patients had
      hemangiomas, and the remaining 15 patients had venous malformations. Sodium
      tetradecyl sulfate was injected solely percutaneously in 49 procedures, by both
      percutaneous and arterial routes in two procedures, and intraarterially only in
      one procedure. Thirteen patients had sclerosis therapy alone, and eight patients
      had sclerosis therapy followed by surgery within 48 hr. RESULTS: Sclerosis
      therapy alone or sclerosis therapy followed by surgery was judged beneficial in
      18 (86%) of 21 patients, including five of the six patients who had hemangiomas
      and 13 of the 15 patients who had venous malformations. Two patients had an
      equivocal response to the therapy, and one patient had no apparent benefit. Three
      of the 21 patients had minor complications (skin ulcers) but no long-term
      sequelae. CONCLUSION: Percutaneous injection of sodium tetradecyl sulfate, either
      alone or before surgery, is a safe and effective method of managing symptomatic
      hemangiomas and venous malformations.

PMID- 9275887
TI  - A sonographically guided technique for central venous access.
AB  - OBJECTIVE: The internal jugular vein (IJV) is an important access to the central
      venous system. We compared sonographically guided technique with the traditional
      anatomic landmark technique for IJV catheterization. SUBJECTS AND METHODS: In a
      prospective randomized trial, 100 patients underwent routine catheterization of
      the IJV (50 patients in the sonography group and 50 patients in the anatomic
      landmark group). Access time, failure rates, and complication rates were
      evaluated. In addition, the physicians' number of years of experience with
      catheter insertion was recorded. RESULTS: Access time was markedly shorter with
      the sonographically guided technique (mean, 15.2 sec; range, 8-76 sec) than with
      the anatomic landmark technique (mean, 51.4 sec; range, 3-820 sec) (p = .001).
      The failure rate was significantly lower with the sonographically guided
      technique (p = .002). Complications were fewer with the sonographically guided
      technique (neck hematoma, 2% versus 10%; plexus irritation, 4% versus 6%; carotid
      artery puncture, 0% versus 12%). We found that the number of years of
      postgraduate clinical training was greater in the group of physicians using the
      anatomic landmark technique. CONCLUSION: The sonographically guided technique is
      associated with less risk and less inconvenience for patients, especially
      critically ill patients, for whom the technique provides fast, safe, and easy IJV
      catheterization.

PMID- 9275888
TI  - Active biplanar MR tracking for biopsies in humans.
AB  - OBJECTIVE: The purpose of this study was to assess the potential of active
      biplanar MR needle tracking in a 0.5-T open-configuration MR system. A needle
      design characterized by an integrated internal signal source was used. To
      evaluate the performance of this new technique in vivo as well as in vitro,
      procedures were performed on patients. CONCLUSION: The results of this study
      prove that the biplanar tracking concept can be applied in a clinical
      environment. The applicability of biplanar tracking is further enhanced by
      integrating an internal signal source.

PMID- 9275889
TI  - Titanium Greenfield filter placement: a retrospective analysis of filter tilting
      comparing access by right internal jugular vein with right femoral vein.

PMID- 9275890
TI  - MR imaging signal-intensity abnormalities after placement of arterial
      endoprostheses.
AB  - OBJECTIVE: Our objectives were to describe changes in T2-weighted MR images of
      patients who had undergone implantation of an endoluminal stent-graft and
      determine the rate of early reocclusion in patients with abnormal MR findings.
      SUBJECTS AND METHODS: Twenty-nine patients with 26 occlusions (average length,
      8.7 +/- 5.6 cm) and three dissections of the superficial femoral artery were
      treated with 45 endoluminal stent-grafts. T2-weighted gradient-echo and T2
      weighted turbo spin-echo MR images were obtained for all patients at 48 hr and at
      4 weeks after stent-graft placement. We reviewed the MR imaging studies to assess
      the extent and severity of tissue alteration at the site of stent-graft
      implantation. RESULTS: Technical success rate of stent-graft placement was 100%.
      Three signal-intensity patterns were seen on MR images obtained at 48 hr: normal
      signal intensity (n = 8), subtle perivascular signal-intensity abnormalities at
      the site of stent-graft implantation (n = 11), and extensive signal-intensity
      abnormalities from the adductor canal to the subcutis (n = 10). Twenty of 21
      patients with abnormal signal intensity on MR images had fevers and pain at the
      implantation site. Clinical signs of deep vein thrombosis, a diagnosis excluded
      on the basis of phlebography, were seen in the 10 patients with extensive signal
      intensity abnormalities. In two of these 10 patients, the superficial femoral
      artery reoccluded within 4 weeks of implantation. MR images obtained at 4 weeks
      showed no signal-intensity abnormalities in any of the 29 patients. CONCLUSION:
      MR findings of perivascular signal-intensity abnormalities after implantation of
      endoluminal stent-grafts are associated with clinical complications such as local
      pain and fever. Care should be taken to avoid confusing the clinical signs of the
      postimplantation syndrome at 48 hr with deep vein thrombosis.

PMID- 9275891
TI  - Cardiac-gated two-dimensional phase-contrast MR angiography of lower extremity
      occlusive disease.
AB  - OBJECTIVE: The purpose of this study was to evaluate our capability to use
      coronally acquired, cardiac-gated two-dimensional phase-contrast MR angiography
      (MRA) to correctly detect and grade arteriosclerotic lesions from the aortic
      bifurcation to the popliteal artery. SUBJECTS AND METHODS: One hundred fifteen
      patients with a total of 253 arteriosclerotic lesions proven by intraarterial
      digital subtraction angiography were examined prospectively by two-dimensional
      phase-contrast MRA. MRA was performed from the aortic bifurcation to the
      popliteal trifurcation. Imaging parameters were TR/TE, 83/9 msec; flip angle, 11
      degrees; matrix, 256 x 192; acquisitions, two; slice thickness, 80 mm; and field
      of view, 320 mm. ECG gating was used routinely and eight to 10 phases were
      acquired during the cardiac cycle. Velocity encoding was set to 30 cm/sec in the
      iliac arteries and to 20 cm/sec in the femoral and popliteal arteries. Detected
      stenoses were graded in the following manner: 1% to less than 50% stenosis, group
      1; 50% to less than 75% stenosis, group 2; 75% to less than 100% stenosis, group
      3; and total occlusion, group 4. RESULTS: All arteriosclerotic lesions were
      revealed by MRA. Two hundred seventeen of 253 lesions were also graded correctly.
      Sensitivity was 95%, specificity was 90%, positive predictive value was 90%, and
      negative predictive value was 96%. The weighted kappa index was (.92).
      Sensitivity and specificity for occlusions were both 100%; for high-grade
      stenoses, 94% and 91%, respectively; for moderate stenoses, 84% and 94%,
      respectively; and for mild stenoses, 79% and 100%, respectively. CONCLUSION: Two
      dimensional phase-contrast MRA can provide MR angiograms with high sensitivity
      and specificity for high-grade stenoses in a reasonable amount of time in
      patients with peripheral artery occlusive disease.

PMID- 9275892
TI  - Gadolinium-enhanced body MR venography with subtraction technique.

PMID- 9275893
TI  - Dynamic cystoproctography: a unifying diagnostic approach to pelvic floor and
      anorectal dysfunction.

PMID- 9275894
TI  - Dynamic cystoproctography of female pelvic floor defects and their
      interrelationships.

PMID- 9275895
TI  - Dynamic MR imaging compared with evacuation proctography when evaluating
      anorectal configuration and pelvic floor movement.
AB  - OBJECTIVE: The aim of this study was to determine the agreement between
      measurements of the anorectal configuration made with dynamic MR imaging and with
      evacuation proctography. SUBJECTS AND METHODS: Ten women with constipation were
      examined sequentially using both standard evacuation proctography and dynamic MR
      imaging. Correlation and agreement between standard measurements of anorectal
      configuration at rest and during straining or evacuation of the rectum were
      evaluated. RESULTS: Significant correlation existed for anorectal junction
      descent (r = .7, p = .023), change in the anorectal angle (r = .78, p = .008),
      the position of the rectal axis on straining (r = .62, p = .032), and rectocele
      depth (r = .82, p = .004). The mean of the measurement differences for anorectal
      junction descent as measured using the two techniques was -0.23 cm (SD, 1.40 cm).
      The mean of the measurement differences for change of the anorectal angle was
      +15.3 degrees (SD, 27.92 degrees). CONCLUSION: Standard measurements of anorectal
      configuration made using evacuation proctography and dynamic MR imaging show
      significant correlation. However, in our study statistical agreement was poor for
      measurement of anorectal junction descent and anorectal angle change as seen on
      imaging obtained with the two techniques.

PMID- 9275896
TI  - Carcinoma of the gallbladder: imaging features with surgical correlation.

PMID- 9275897
TI  - Gastric lesions: evaluation with three-dimensional images using helical CT.

PMID- 9275898
TI  - Retractile mesenteritis: small-bowel radiography, CT, and MR imaging.

PMID- 9275899
TI  - Nontumorous hepatic pseudolesion around the falciform ligament: prevalence on
      gadolinium chelate-enhanced MR examination.
AB  - OBJECTIVE: Our objective was to determine the prevalence of nontumorous hepatic
      pseudolesions seen around the falciform ligament on dynamic spoiled three
      dimensional (3D) gradient-recalled echo (GRE) MR imaging obtained during i.v.
      injection of a gadolinium chelate. SUBJECTS AND METHODS: The gadolinium chelate
      enhanced spoiled 3D GRE examinations of the liver of 103 patients were
      prospectively analyzed by two readers for the presence of a nontumorous hepatic
      pseudolesion around the falciform ligament to determine the prevalence of this
      finding. For all pseudolesions, pathologic examination or follow-up imaging
      studies excluded true tumors. RESULTS: A total of 15 nontumorous hepatic
      pseudolesions were found on 13 (13%) of 103 examinations. The size of
      pseudolesions ranged from 5 to 15 mm (mean, 9 mm). Twelve pseudolesions were
      located in segment IV, and three were in segment III. On two MR examinations, two
      pseudolesions (one in segment IV and one in segment III) were found. Fourteen
      (93%) of 15 pseudolesions were seen during the arterial phase of the bolus
      injection. All pseudolesions (100%) were seen during the portal phase, and one
      pseudolesion (7%) remained visible during the equilibrium phase. The presence of
      true tumors was excluded in one case by pathologic examination and in twelve
      cases by follow-up imaging examinations. CONCLUSION: Nontumorous hepatic
      pseudolesions around the falciform ligament are not rarely seen on gadolinium
      chelate-enhanced spoiled 3D GRE examinations. Thus, recognition of these
      pseudolesions is crucial because they may be misinterpreted as true tumors.

PMID- 9275900
TI  - Compensated cirrhosis due to viral hepatitis: using MR imaging to predict
      clinical progression.
AB  - OBJECTIVE: The goal of our study was to determine the relative value of multiple
      MR features in predicting clinical progression of disease in patients with
      compensated cirrhosis. MATERIALS AND METHODS: The MR examinations of 23 patients
      with compensated cirrhosis (Child A) were retrospectively reviewed independently
      by two radiologists and correlated with clinical progression after follow-up of
      all patients for more than 12 months each (12-87 months: average, 39 months) by
      the same experienced hepatologist. Clinical progression was defined as an
      increase of the Child grade or the Pugh score by at least two points (5- to 15
      point scale). In the initial MR study of each patient, the following MR findings
      were assessed by each radiologist independently: volume indexes of the spleen and
      each segment of the liver (based on three-axis measurements), nodular surface,
      regenerative nodules, ascites, iron or fat deposition, and varices or
      collaterals. RESULTS: The volume index of the spleen was the most accurate
      predictor of clinical progression (p = .001), the next most accurate was the
      number of sites of varices or collaterals (p = .002), and the third most accurate
      was the ratio of caudate lobe to right lobe volume index (p = .02). Other MR
      findings failed to correlate with clinical progression. CONCLUSION: As revealed
      on MR imaging, the volume index of the spleen, the severity of varices, and the
      volume index ratio of caudate lobe to right lobe can be used to help predict
      clinical progression of disease in patients with compensated cirrhosis.

PMID- 9275901
TI  - MR cholangiography in the examination of patients with biliary-enteric
      anastomoses.
AB  - OBJECTIVE: The aim of our study was to determine the role of MR cholangiography
      in the noninvasive examination of patients with biliary-enteric anastomoses.
      SUBJECTS AND METHODS: Twenty-four patients (nine men and 15 women; mean age, 68.9
      years old) with biliary-enteric anastomoses underwent MR cholangiography. We used
      a fat-suppressed three-dimensional turbo spin-echo sequence (3000/700 [TR/TE];
      echo train length, 128) with no breath-hold, optimized with a 0.5-T magnet.
      Imaging studies were performed because of scheduled follow-up (five patients),
      persistent jaundice (six patients), cholangitis and abnormal liver function
      (eight patients), and a combination of transient jaundice, epigastric pain, and
      abnormal liver function (five patients). RESULTS: Image quality was graded from
      optimal to good in 21 (88%) of 24 cases and poor in three (13%) of 24 cases. The
      degree of bile duct dilatation was correctly assessed, with complete agreement
      between the two observers in all cases. MR cholangiography correctly showed bile
      duct irregularities in six of the eight patients with cholangitis (kappa = .59),
      anastomotic strictures in all 19 patients with strictures (kappa = .86), and 3-
      to 15-mm stones in nine of 10 patients (kappa = .95). A slight overestimation of
      the strictures occurred in four of the 19 cases with strictures. CONCLUSION: MR
      cholangiography is a reliable imaging technique for the examination of patients
      with biliary-enteric anastomoses.

PMID- 9275903
TI  - Diagnosis and management of patients with complicated cystic lesions of the
      kidney.

PMID- 9275902
TI  - CT of cystic renal masses: analysis of diagnostic performance and interobserver
      variation.
AB  - OBJECTIVE: Our objective was to assess the clinical usefulness and interobserver
      variability of the Bosniak classification scheme for characterizing a series of
      pathologically proven cystic renal lesions imaged with CT. MATERIALS AND METHODS:
      Seventy pathologically proven cystic renal masses (38 benign, 32 malignant) in 46
      patients were reviewed independently by three radiologists. The cystic masses
      were categorized by each reviewer according to both the Bosniak classification
      and the receiver operating characteristic (ROC) analysis. Both the individual
      results for each reader and the pooled results for all three readers were
      analyzed. Interobserver agreement and discordance in classifying lesions as
      Bosniak categories I-II or III-IV were assessed. RESULTS: The distribution of the
      70 lesions (based on the average of the three readers) was 22 Bosniak I (0%
      malignant), eight Bosniak II (13% malignant), 11 Bosniak III (45% malignant), and
      29 Bosniak IV (90% malignant). All readers agreed on the Bosniak classification
      in 59%, or 41 of the 70 lesions (I, 17; II, one: III, four: and IV, 19). Eleven
      (16%) of the 70 lesions were classified as Bosniak I or II by one reader and as
      Bosniak III or IV by at least one other reader. The area under the curve for the
      pooled ROC analysis was calculated to be 0.957. Individual reader values ranged
      from 0.914 to 0.981. The sensitivities, specificities, and accuracies for the
      three readers ranged from 94% to 100%, 71% to 92%, and 84% to 93%. Assessment of
      interobserver variability by kappa analysis yielded scores of .571 and .477 for
      the Bosniak and ROC analyses, respectively. CONCLUSION: Overall, the Bosniak
      classification scheme is useful for evaluating renal masses: however,
      interobserver variation in distinguishing. Bosniak II and Bosniak III lesions may
      present difficulties in recommending surgical versus conservative management.

PMID- 9275904
TI  - Malignant lymphoma of the testis.

PMID- 9275905
TI  - Imperforate syringoceles of the bulbourethral duct: appearance on urethrography,
      sonography, and CT.

PMID- 9275906
TI  - Clinical application of the Ottawa ankle rules for the use of radiography in
      acute ankle injuries: an independent site assessment.
AB  - OBJECTIVE: Previous studies show that the clinical criteria known as the Ottawa
      ankle rules (OAR), used for determining the need for radiographs of the ankle
      when a fracture is suspected, have a sensitivity of 100%, a specificity of 50%,
      and an overall reduction in radiographs of the ankle of 28%. The purpose of this
      study was to further assess the clinical usefulness of the OAR when implemented
      in an emergency department of a level 1 trauma center. SUBJECTS AND METHODS: Over
      a 1-year period, all patients who were between 18 and 55 years old and who
      presented to the emergency department with blunt ankle trauma were examined by
      emergency department clinicians who used the OAR to determine the need for
      ordering ankle radiographs. RESULTS: Of 926 patients with blunt ankle trauma, 759
      met OAR criteria for ordering radiographs of the ankle. Of these patients, 152
      were found to have a fracture. Another 167 of the patients were determined not to
      need ankle radiographs. Through either telephone contact or medical records
      review. 152 (91%) of these 167 patients were successfully followed up for the
      purpose of detecting any missed fractures. Two missed fractures were discovered,
      but only one required plaster immobilization. Based on these numbers, overall
      sensitivity using the OAR was 99% (confidence interval, 95-100%), and specificity
      was 22%. We found an overall 16% reduction in the number of ankle films ordered.
      CONCLUSION: When implemented at a level 1 trauma center, the OAR can adequately
      screen for ankle fractures.

PMID- 9275907
TI  - Anterolateral soft-tissue impingement in the ankle: diagnosis using MR imaging.
AB  - OBJECTIVE: This study was performed to elucidate the MR imaging findings and
      pitfalls for the diagnosis of anterolateral soft-tissue impingement in the ankle,
      a cause of chronic ankle pain that can be relieved by arthroscopic resection.
      MATERIALS AND METHODS: We retrospectively reviewed MR imaging examinations of 18
      patients with arthroscopically confirmed anterolateral ankle impingement. The MR
      images of 18 additional subjects with symptoms that could mimic anterolateral
      impingement, but who had a surgically confirmed alternate diagnosis (instability,
      peroneal tendon injury, osteochondral defect, normal arthroscopy) and no evidence
      of impingement at arthroscopy, served as controls. RESULTS: On the MR imaging
      studies, nine patients had an ankle effusion, eight of whom showed an abnormal
      soft-tissue structure in the anterolateral gutter, 2-15 mm in maximal diameter.
      No soft-tissue mass was seen in the patients without joint fluid. Four control
      subjects with instability had a similar soft-tissue structure in the
      anterolateral gutter, but in the control subjects the finding represented a
      portion of the torn anterior talofibular ligament. CONCLUSION: Anterolateral soft
      tissue impingement of the ankle can be suggested by MR imaging when fluid in the
      lateral gutter outlines an abnormal soft-tissue structure separate from the
      anterior talofibular ligament.

PMID- 9275909
TI  - Sonographic guidance of needle position for MR arthrography of the shoulder.

PMID- 9275908
TI  - Using abduction and external rotation of the shoulder to increase the sensitivity
      of MR arthrography in revealing tears of the anterior glenoid labrum.
AB  - OBJECTIVE: The purpose of this study was to compare oblique axial MR arthrograms
      obtained with the patient's shoulder in abduction and external rotation (ABER)
      position with conventional axial MR arthrograms obtained with the patient's arm
      in neutral position and the shoulder not rotated in revealing tears of the
      anterior glenoid labrum (AGL). SUBJECTS AND METHODS: MR arthrography of the
      shoulder that included an additional oblique axial imaging sequence with the
      patient in the ABER position was performed in 256 patients. Assessment of AGL
      integrity with patients in both conventional axial and ABER positions was made
      before surgery. These assessments were compared with the surgical findings.
      RESULTS: Of the 92 patients who underwent surgery, AGL tears were found in 27.
      Conventional axial MR arthrograms revealed 13 tears (sensitivity, 48%;
      specificity, 91%). A separate review of MR arthrograms obtained with patients in
      the ABER position revealed 24 tears (sensitivity, 89%; specificity, 95%).
      Reviewed together, axial MR arthrograms and MR arthrograms obtained with patients
      in the ABER position revealed 26 tears (sensitivity, 96%; specificity, 97%).
      CONCLUSION: Oblique axial MR arthrograms obtained with the patient's shoulder in
      the ABER position were significantly more sensitive in revealing AGL tears (p =
      .005) than were conventional axial MR arthrograms obtained with the patient's aim
      in a neutral position and the shoulder not rotated.

PMID- 9275910
TI  - Diseases of the pubis and pubic symphysis: MR imaging appearances.
AB  - MR imaging may provide detailed information as to the precise nature of a wide
      range of abnormalities occurring in the pubic symphysis region. Conventional
      radiographs should, however, be performed initially because MR imaging is not
      always indicated and without complementary radiographs may result in erroneous
      diagnosis.

PMID- 9275912
TI  - Fluid-attenuated inversion recovery MR imaging: identification of protein
      concentration thresholds for CSF hyperintensity.
AB  - OBJECTIVE: Using human volunteers and phantoms emulating CSF, we analyzed the
      effects of varying protein concentration on the signal intensity of saline
      solution. Also, for different fluid-attenuated inversion recovery (FLAIR)
      sequences, we compared protein concentration thresholds above which the signal
      from these solutions becomes hyperintense to that from brain parenchyma. SUBJECTS
      AND METHODS: Nine albumin solutions of varying concentrations (3.9 mg/dl to 2500
      mg/dl) were imaged using fast FLAIR MR sequences (TR, 6000 msec: inversion time,
      1730 msec: echo train length, 20) at different effective TEs (110, 150, 200, and
      250 signal-to-noise ratios from the different albumin solutions versus albumin
      concentration were generated and correlated with average signal-to-noise ratios
      from brain parenchyma and CSF. RESULTS: We saw a gradual increase in signal-to
      noise ratios from the albumin solutions as a function of albumin concentration.
      As the effective TE increased, the point of intersection between the plots and
      the average signal-to-noise ratio from brain parenchyma occurred at lower albumin
      concentrations. CONCLUSION: FLAIR MR imaging is potentially useful to evaluate
      pathologic conditions that increase CSF protein concentration. Using phantoms and
      healthy volunteers, we defined a protein concentration threshold above which the
      signal from saline solutions becomes hyperintense to that from brain parenchyma.
      This threshold depends on the effective TE used in the FLAIR sequence and is 250
      mg/dl for an effective TE of 110 msec, 125 mg/dl for 150 msec. 110 mg/dl for 200
      msec, and 95 mg/dl for 250 msec.

PMID- 9275911
TI  - Osteonecrosis after contact neodymium:yttrium aluminum garnet arthroscopic laser
      meniscectomy.
AB  - OBJECTIVE: The purpose of this report is to describe two cases of osteonecrosis
      that occurred after arthroscopic meniscectomy with a contact neodymium:yttrium
      aluminum garnet laser system. The patients developed increasing knee pain and
      disability 5 months and 6 months after laser meniscectomy. MR imaging showed
      subchondral osteonecrosis in the femoral condyle and tibial plateau immediately
      adjacent to the site of laser meniscectomy in both patients. One patient required
      a total knee replacement to alleviate knee symptoms, and the other patient
      required a tibial osteotomy and surgical elevation of collapsed tibial articular
      surface. CONCLUSION: To our knowledge, this complication of laser arthroscopic
      meniscectomy has not been reported in the radiology literature. The clinical and
      MR imaging features of this important complication are described and possible
      causative mechanisms are discussed.

PMID- 9275913
TI  - Real-time monitoring of laser diskectomies with a superconducting, open
      configuration MR system.
AB  - OBJECTIVE: The objective of our study was to assess the ability of a 0.5-T
      superconducting, open-configuration MR system to guide laser diskectomies. The
      study was performed ex vivo on six human cadavers as well as in vivo on three
      patients. CONCLUSION: The macroscopic size of necrosis correlated well with the
      monitored temperature spread (r2 = .76-.85). After MR-guided introduction of the
      laser fiber into the targeted disk space, temperature spread was visualized in
      all subjects.

PMID- 9275914
TI  - Complications of cervical spine fusion: imaging features.

PMID- 9275915
TI  - Qualitative MR imaging of refractory temporal lobe epilepsy requiring surgery:
      correlation with pathology and seizure outcome after surgery.
AB  - OBJECTIVE: The purpose of this study was to compare MR imaging findings with
      histologic findings of either hippocampal sclerosis or gliosis in patients with
      intractable temporal lobe epilepsy requiring surgery and to correlate MR imaging
      findings with seizure outcome after surgery and with clinical parameters such as
      febrile seizure history. MATERIALS AND METHODS: A retrospective study of MR scans
      of 66 patients with medically refractory temporal lobe epilepsy requiring surgery
      was performed. Qualitative diagnosis was done by visual inspection of MR images.
      MR imaging findings of hippocampal atrophy, signal intensity changes, and
      segmental findings were correlated with histopathology and with neuronal density.
      The final MR imaging diagnosis was also correlated with seizure outcome after
      surgery and with febrile seizure history. RESULTS: Histologic findings consisted
      of hippocampal sclerosis in 55 patients and nonspecific gliosis in 11 patients.
      Two variables, MR imaging findings of hippocampal sclerosis (hippocampal atrophy
      or signal intensity change) and a febrile seizure history, were significantly
      associated with hippocampal sclerosis. MR images of nonspecific gliosis usually
      showed normal findings, although some cases showed mild hippocampal atrophy. When
      comparing MR imaging findings with histology, our observers achieved
      sensitivities of 87-98% and specificities of 45-100%. In patients with successful
      outcomes after surgery, sensitivity ranged from 85% to 98% for MR imaging
      findings suggesting hippocampal sclerosis, specificity ranged from 17% to 85%,
      and positive predictive values ranged from 82% to 90%. CONCLUSION: Qualitative
      visual analysis of MR images correlates well with histologic findings, febrile
      seizure history, and seizure outcome after surgery. MR imaging findings and
      febrile seizure history help differentiate between hippocampal sclerosis and
      nonspecific gliosis, two similar clinical conditions associated with temporal
      lobe epilepsy that often have different outcomes after surgery.

PMID- 9275917
TI  - Characterization of intracranial aneurysms using CT angiography.

PMID- 9275916
TI  - Typical and atypical MR imaging features of intracranial epidermoid tumors.
AB  - OBJECTIVE: We categorized the MR imaging characteristics of intracranial
      epidermoid tumors. MATERIALS AND METHODS: MR images from 23 cases of intracranial
      epidermoid tumors were reviewed retrospectively. Signal intensities of tumor
      relative to surrounding structures were noted, as were the internal architecture
      of the tumors and the presence and degree of hydrocephalus. RESULTS: Seventeen
      (74%) of 23 cases of intracranial epidermoid tumors were revealed as slightly
      hyperintense relative to CSF on T1-weighted MR images. Nineteen (95%) of 20 cases
      were hyperintense relative to CSF on proton density-weighted MR images. Fifteen
      (65%) of 23 cases were isointense to CSF on T2-weighted MR images, whereas the
      remaining eight cases (35%) were hyperintense to CSF on T2-weighted MR images.
      One (4%) of 23 cases showed signal intensity that was isointense to CSF on all
      pulse sequences. Fifteen (65%) of 23 cases showed heterogeneous signal
      characteristics on either T1-weighted or proton density-weighted MR images, or
      both. Eight (35%) of 23 cases showed a rim of hyperintensity on proton density
      weighted MR images. Five (33%) of the 15 cases that received gadolinium showed
      rim enhancement. Five (22%) of 23 cases were multilocular, with different regions
      of tumors showing highly variable imaging characteristics. Two (9%) of 23 cases
      showed high signal intensity on T2-weighted MR images in the adjacent brain
      parenchyma. Two (9%) of 23 cases showed mild hydrocephalus. Six (43%) of 14
      tumors that either originated in or secondarily involved the cerebellopontine
      angle also extended into the ipsilateral Meckel's cave. CONCLUSION: On T1-,
      proton density-, and T2-weighted MR images intracranial epidermoid tumors usually
      showed heterogeneous signal intensity that was hyperintense to CSF. On all spin
      echo pulse sequences epidermoid tumors with signal characteristics isointense to
      CSF were unusual. Hydrocephalus, even in the setting of marked displacement and
      compression of the brainstem, was not usually seen on MR imaging. Meckel's cave
      was often involved secondarily with epidermoid tumors that involved the
      cerebellopontine angle.

PMID- 9275918
TI  - MR imaging of stereotaxic pallidotomy and thalamotomy.

PMID- 9275920
TI  - Can the results obtained with a specific gradient-recalled echo (GRE) sequence on
      a machine of vendor A (e.g., fast low-angle shot technique [FLASH].

PMID- 9275919
TI  - How well does a history of seafood allergy predict the likelihood of an adverse
      reaction to i.v. contrast material?

PMID- 9275921
TI  - What diagnostic tests are available for screening the rectum, the colon, and the
      lower gastrointestinal tract?

PMID- 9275922
TI  - Re: Detection with MR imaging of residual tumor in the breast soon after surgery.

PMID- 9275923
TI  - Increased medullary densities.

PMID- 9275924
TI  - Detection of cartilage lesions with fat-suppressed three-dimensional spoiled
      gradient-echo MR imaging.

PMID- 9275925
TI  - Talc pleurodesis: a matter of priority.

PMID- 9275926
TI  - Juvenile papillomatosis of the breast (Swiss cheese disease)

PMID- 9275927
TI  - Enterohemorrhagic colitis caused by Escherichia coli: CT findings.

PMID- 9275928
TI  - Re: Anaphylactic shock during a routine upper gastrointestinal series.

PMID- 9275929
TI  - Re: Emphysematous pyelonephritis producing rapid gas formation.

PMID- 9275930
TI  - Carcinoma en cuirasse: uncontrolled local recurrence of breast carcinoma after
      transverse rectus abdominis myocutaneous flap reconstruction.

PMID- 9275931
TI  - The hyperdense liver and spleen: a CT manifestation of barium embolization
      through a duodenocaval fistula.

PMID- 9275932
TI  - Sonographic features of abdominal wall endometriosis.

PMID- 9275933
TI  - Helical CT findings of acute renal cortical necrosis in hemolytic uremic
      syndrome.

PMID- 9275934
TI  - Adenomyoepithelioma of the breast in a male.

PMID- 9275935
TI  - Episiotomy and perineal tears: cause and effect.

PMID- 9275936
TI  - Controversies in spirometry.

PMID- 9275937
TI  - Controversies in spirometry.

PMID- 9275938
TI  - Wife abuse: universal screening.

PMID- 9275939
TI  - Confusion still surrounds third-party forms.

PMID- 9275941
TI  - Fishing expeditions in doctors' offices.

PMID- 9275940
TI  - Students work to foster tolerance.

PMID- 9275942
TI  - Measuring behaviour in children with high cholesterol levels.

PMID- 9275944
TI  - Risk of HIV infection from blood transfusion in Montreal.
AB  - OBJECTIVES: To determine the incidence (including associated donor
      characteristics and time trends) of HIV infection among repeat blood donors and
      to estimate the risk of HIV transmission from blood transfusion in Montreal and
      in Canada as a whole. DESIGN: Retrospective cohort analysis. SETTING: Montreal
      Centre Blood Transfusion Service. PARTICIPANTS: People who donated blood at least
      twice after Nov. 1, 1985, and at least once from Apr. 1, 1989, to Mar. 31, 1993.
      INTERVENTION: Blood was screened for HIV by enzyme-linked immunosorbent assay and
      results were confirmed by Western blot analysis. OUTCOME MEASURES: Incidence
      density (the incidence rate per person-time) of HIV infection among repeat blood
      donors by sex, age group and region of residence, and incidence density and risk
      among first-time donors and for Canada as whole. RESULTS: There were 200,196
      eligible donors and 432,631 person-years (PY) of observation. From 1989 to 1993,
      there were 18 HIV seroconversions among repeat donors. The crude incidence
      density was 3.3 per 100,000 PY (95% confidence interval [CI] 1.8 to 5.4 per
      100,000 PY); it was 4.9 per 100,000 PY among men and 0.61 per 100,000 PY among
      women. Age-specific incidence per 100,000 PY was 2.5 among those 12-29 years of
      age, 5.1 among those 30-49, 2.9 among those 40-49, and 1.4 among those 50 and
      older. Based on an estimated mean "window period" (from when a donor's blood is
      capable of transmitting HIV until detectable antibody appears) of 25 days, the
      current risk of HIV infection from repeat donors in the window period is
      estimated at 1 in 440,000. Inclusion of blood units from first-time donors
      produces an overall risk of 1 in 390,000 (95% CI 1 in 250,000 to 655,000). The
      estimated risk per blood unit in Canada as a whole is 1 in 913000 (95% CI 1 in
      507,000 to 2,050,000). CONCLUSIONS: This "sentinel" population of repeat blood
      donors is subject to important trends in HIV spread. Therefore, estimating the
      incidence density of HIV infection in repeat donors provides insight into the
      epidemiologic characteristics of HIV infection at minimal expense. As a result of
      measures to improve blood safety, including HIV testing, the incidence of HIV
      infection among blood donors in Canada is low and the risk of HIV transmission
      from transfusion is extremely small, although not zero.

PMID- 9275945
TI  - A role for the sick role. Patient preferences regarding information and
      participation in clinical decision-making.
AB  - OBJECTIVE: To assess whether patient preferences regarding information and
      participation in decision-making about treatment options are related to patient
      characteristics and the context of the decision. Other studies have compared
      decision-making preferences in patients with cancer and healthy subjects, or in
      different contexts among patients in the same group. This study combined these
      designs. DESIGN: Questionnaire completed by the subjects. SETTING: Outpatient
      clinic of a university hospital. PARTICIPANTS: A consecutive sample of 55
      patients with cancer treated at a radiotherapy clinic, 53 persons accompanying
      them, a consecutive sample of 53 patients visiting a surgical outpatient clinic
      for a nonmalignant condition and 36 persons accompanying them. MAIN MEASURES:
      Preferences regarding information and participation in decision-making in general
      and with respect to 4 vignettes that described different diseases of varying
      seriousness, varying treatment options and side effects. RESULTS: Older patients
      and men were more likely to let the physician make decisions regarding their
      treatment. Patients, as compared with nonpatients (their companions), were more
      likely to prefer a passive role regarding treatment decisions. No differences
      were seen between patients with cancer and patients with nonmalignant conditions.
      Also, no effect was observed in relation to the decision-making situations
      described in the vignettes. Of the patients who preferred more information, a
      substantial proportion still preferred a passive decision-making role.
      CONCLUSION: The lack of strong predictors of a preferred decision-making role
      implies that clinicians need to assess every patient individually to determine
      what role he or she prefers. The finding that the patients preferred a more
      passive role than their companions suggests that the "sick role" influences the
      preference regarding participation more strongly than the type of decision to be
      made or the presence of a life-threatening disease. This hypothesized shift in
      preference among subjects who are sick implies that these patients need
      encouragement to participate.

PMID- 9275946
TI  - HIV in the blood supply: nothing to fear but fear itself.

PMID- 9275947
TI  - Should physicians discourage patients from playing the sick role?

PMID- 9275948
TI  - Mainstreaming methadone maintenance treatment: the role of the family physician.

PMID- 9275949
TI  - Methadone maintenance treatment: a Canadian perspective.

PMID- 9275950
TI  - Recipes or roadmaps? Instead of rejecting clinical practice guidelines as
      "cookbook" solutions, could physicians use them as roadmaps for the journey of
      patient care?

PMID- 9275951
TI  - The "Supremes" decide on assisted suicide: what should a doctor do?

PMID- 9275952
TI  - Translating guidelines into practice. A systematic review of theoretic concepts,
      practical experience and research evidence in the adoption of clinical practice
      guidelines.
AB  - OBJECTIVE: To recommend effective strategies for implementing clinical practice
      guidelines (CPGs). DATA SOURCES: The Research and Development Resource Base in
      Continuing Medical Education, maintained by the University of Toronto, was
      searched, as was MEDLINE from January 1990 to June 1996, inclusive, with the use
      of the MeSH heading "practice guidelines" and relevant text words. STUDY
      SELECTION: Studies of CPG implementation strategies and reviews of such studies
      were selected. Randomized controlled trials and trials that objectively measured
      physicians' performance or health care outcomes were emphasized. DATA EXTRACTION:
      Articles were reviewed to determine the effect of various factors on the adoption
      of guidelines. DATA SYNTHESIS: The articles showed that CPG dissemination or
      implementation processes have mixed results. Variables that affect the adoption
      of guidelines include qualities of the guidelines, characteristics of the health
      care professional, characteristics of the practice setting, incentives,
      regulation and patient factors. Specific strategies fell into 2 categories:
      primary strategies involving mailing or publication of the actual guidelines and
      secondary interventional strategies to reinforce the guidelines. The
      interventions were shown to be weak (didactic, traditional continuing medical
      education and mailings), moderately effective (audit and feedback, especially
      concurrent, targeted to specific providers and delivered by peers or opinion
      leaders) and relatively strong (reminder systems, academic detailing and multiple
      interventions). CONCLUSIONS: The evidence shows serious deficiencies in the
      adoption of CPGs in practice. Future implementation strategies must overcome this
      failure through an understanding of the forces and variables influencing practice
      and through the use of methods that are practice- and community-based rather than
      didactic.

PMID- 9275954
TI  - Gather ye rosebuds while ye may--but avoid the mushrooms.

PMID- 9275953
TI  - Primary prevention of heart disease and stroke: a simplified approach to
      estimating risk of events and making drug treatment decisions.
AB  - Long-term population-based studies have identified and quantified risk factors
      for cardiovascular and cerebrovascular (CCV) events. In addition, a number of
      well-designed clinical trials have shown that various drug therapies that reduce
      these factors decrease the risk of some CCV events. In the practice of evidence
      based medicine, data from clinical trials should inform treatment decisions. The
      clinician and patient, however, are faced with the difficult task of assessing
      the patient's particular risk and likelihood of benefit on the basis of the
      results of large, randomized trials. To assist clinicians and their patients in
      arriving at treatment decisions, the authors provide simple nomograms for
      estimating the risk of a CCV event for an individual patient and suggest an
      approach to estimating the potential benefit of drug therapy for primary
      prevention.

PMID- 9275955
TI  - Death of phone service indicates Canadians not willing to pay for medical advice.
AB  - The two physicians who started Canada's first national pay-per-use medical-advice
      line closed the service after determining that Canadians are not willing to pay
      directly for their medical services. The issue of public versus private payments
      will likely be raised during the CMA's annual meeting later this month.

PMID- 9275956
TI  - FPs have vital role in ensuring success of breast cancer screening programs.
AB  - SCREENING IS THE ONLY PROVEN STRATEGY for reducing breast cancer mortality in
      women older than 50. Over the last 9 years, 8 provinces and 2 (territories have
      established independent dedicated mammography programs. A recent workshop on
      screening programs was told that family physicians play a crucial role in the
      ultimate success of these programs because of their referral role.

PMID- 9275957
TI  - The proposed tobacco deal: not so fast.

PMID- 9275958
TI  - Long QT interval in a young woman with severe weakness.

PMID- 9275959
TI  - Milky ascites in a former whiskey runner.

PMID- 9275960
TI  - Another cause of hyperhomocysteinemia.

PMID- 9275961
TI  - Statin drugs: a double-edged sword?

PMID- 9275963
TI  - Case in point. Lipemia retinalis.

PMID- 9275962
TI  - NeuroAIDS: diagnosis and management.
AB  - Neurologic disorders are present in 15% to 30% of AIDS patients. The physiologic
      isolation imposed by the brain and blood-brain barrier have limited
      characterization of the disorders and assessment of therapy. Only time will tell
      whether the multidrug antiretroviral regimens that have shown such success in
      controlling HIV in the systemic compartment will be equally effective in
      suppressing brain viremia.

PMID- 9275964
TI  - X-ray evaluation of the knee.

PMID- 9275965
TI  - Information strategies that work for physicians.

PMID- 9275966
TI  - Hypoxemia and recurrent epistaxis in an 81-year-old woman.

PMID- 9275967
TI  - An etiologic approach to obesity.
AB  - Emotional or social barriers to a healthy diet and physical activity are typical
      in obese patients. Counseling can help identify the barriers and improve either
      the situation or patients' response to it. Long-term success most often occurs
      when there is a cognitive shift from focusing on weight to focusing on health.
      Drugs can be a useful adjunct but cannot substitute for lifestyle modification.

PMID- 9275969
TI  - Current concepts in aortic stenosis.
AB  - Noninvasive cardiac imaging techniques now make it possible to determine the
      morphologic and hemodynamic status of patients with aortic stenosis, even in
      early asymptomatic stages of the disease. This is particularly important since
      the prognosis is generally poor once symptoms are apparent and since replacement
      of the aortic valve is usually the only recourse when stenosis is severe.

PMID- 9275968
TI  - Confounding factors in the management of myositis.
AB  - Management of myositis is complicated by the lack of a clear understanding of the
      disease and the lack of clear diagnostic and therapeutic guidelines. These issues
      are of particular concern since there can be serious side-effects of first-line
      therapy and, in the case of dermatomyositis, an associated risk of cancer.

PMID- 9275970
TI  - A comprehensive approach to organ donation.
AB  - While the demand for organ transplants has increased greatly, actual organ
      donation has failed to keep pace. Educating the public and raising the awareness
      of the health care profession can help even the odds.

PMID- 9275972
TI  - Intermittent dysphagia in a causal smoker.

PMID- 9275971
TI  - Brutalized child, brutal killer.

PMID- 9275973
TI  - Case in point. Salmon patch-hemorrhages (nonproliferative retinopathy associated
      with sickle-cell disease).

PMID- 9275974
TI  - Iodinated contrast material in uroradiology. Choice of agent and management of
      complications.
AB  - Many conditions seen by urologists require imaging examinations with iodinated
      radiographic contrast material as a key part of the primary evaluation of the
      patient. A basic understanding of contrast media, risks of administration, choice
      of agents, and premedication regimens for high-risk patients, is beneficial in
      helping patients prepare for their examinations. Urologists may be the primary
      physicians administering contrast material or may be working with radiologists in
      the care of patients receiving contrast agents. Because contrast reactions may
      occur unexpectedly, even during examinations in which the agents are not given
      intravenously, urologists should be able to recognize and treat the various types
      of adverse reactions.

PMID- 9275975
TI  - Radiologic evaluation of small and indeterminant renal masses.
AB  - A common problem in radiologic and urologic practice today is what to do with the
      small or indeterminant renal mass. Whether found incidentally or sought after
      because of patient symptomatology, these lesions present a challenge in diagnosis
      and management. This article outlines the scope of the problem, illustrates
      representative lesions, suggests imaging and management strategies culled from
      personal experience, and provides a review of available literature.

PMID- 9275976
TI  - Imaging approach to staging of renal cell carcinoma.
AB  - Current imaging techniques, especially CT and MR imaging, make accurate
      preoperative staging of renal cell carcinoma possible. Because surgery provides
      the only effective therapy and because survival depends on local and distant
      extent, precise staging is critical for preoperative planning and prognosis. This
      article reviews the advantages, limitations, accuracy, and pitfalls of each of
      the imaging approaches to staging renal cell carcinoma, concentrating on CT and
      MR imaging. This information then is summarized in a suggested overall approach
      to staging renal cell carcinoma.

PMID- 9275978
TI  - Imaging and radiologic management of upper urinary tract infections.
AB  - Most infections of the upper urinary tract respond promptly to antibiotic therapy
      and imaging is not necessary. Patients with urinary obstruction, diabetes, or
      immunocompromise are more likely to develop complicated infection, abscess, or
      have unusual organisms. Chronic granulomatous processes involving the kidney are
      usually related to recurrent bacterial infections. Again, stone disease or
      obstruction is often an underlying problem. In those patients who do not respond
      promptly to treatment or have a more complicated clinical picture, imaging can
      assess the severity and extent of disease. CT scan is the study of choice for
      diagnostic evaluation in these patients and directs percutaneous intervention
      when appropriate. Placement of drainage catheters is often curative but also may
      allow the patient to stabilize until surgical treatment is accomplished. One
      exception is the diagnosis of pyonephrosis, which may be accomplished more easily
      by ultrasound. In these cases, PCN placement is generally needed and is performed
      under fluoroscopic guidance. Ultimately, however, definitive surgical
      intervention often is needed to relieve the underlying obstruction.

PMID- 9275977
TI  - Current concepts and controversies in imaging of renal cystic diseases.
AB  - Renal cystic disease compromises a diverse group of inherited and acquired
      entities. This article reviews the clinical, pathologic, and radiologic findings
      of eight renal cystic diseases. For each entity, the current concepts of
      pathogenesis and pathophysiology are discussed. When appropriate, controversies
      concerning terminology, management, and malignant potentials are addressed. Renal
      cystic diseases that are discussed include autosomal dominant and autosomal
      recessive polycystic kidney disease, medullary sponge kidney, medullary cystic
      disease, multicystic, dysplastic kidney, von Hippel-Lindau disease, acquired
      cystic kidney disease, and tuberous sclerosis.

PMID- 9275979
TI  - Acute urinary tract obstruction. Imaging update.
AB  - Although urinary tract obstruction is an age old problem with IVU the time
      honored imaging technique of choice, recent advances in renal ultrasonography and
      abdominal and pelvic CT scanning have advanced these alternative modalities to
      the forefront. No rigid algorithm for renal obstruction is recommended, because
      the utilization of these techniques is in a state of flux. The use of one
      modality over another as a first-line imaging technique likely will depend on the
      equipment availability and expertise of a given institution. The choice also may
      be guided by each institution's cost of each type of examination. Although a role
      for the IVU remains in the evaluation of acute renal obstruction, ultrasonography
      and CT scan have emerged as alternative primary screening tools. Undoubtedly, the
      future will bring further changes in our assessment of renal obstruction. The
      cost effectiveness and definitiveness of evaluation likely will become more
      important driving factors than they have been in the past. The radiologist and
      urologist together must assess available imaging techniques, their effectiveness,
      and the institution's expertise to develop a cost-effective and efficient system
      for assessment of renal obstruction.

PMID- 9275980
TI  - What is new in bladder cancer imaging.
AB  - Treatment and prognosis of urinary bladder cancer largely are determined by the
      tumor stage and presence of metastases. MR imaging and clinical staging
      complement each other. MR imaging is the most accurate technique for
      differentiating the various stages of deep tumor infiltration and detection of
      metastases, whereas clinical staging is the best technique for differentiating
      between postbiopsy effects and the various stages of superficial tumors. The role
      of MR imaging in staging of this disease and monitoring of therapy is reviewed
      and illustrated. Finally, the authors present an overview of current and future
      applications of this technique.

PMID- 9275981
TI  - Imaging of adrenal masses.
AB  - Most adrenal masses are detected on CT scans, but only a minority has morphologic
      features that are characteristic of a specific histologic diagnosis. In patients
      with clinical or biochemical features of a hyperfunctioning adrenal syndrome, CT
      detection of a unilateral adrenal mass typically leads to surgical resection,
      although functional assessment of the mass with iodomethylnorcholesterol or MIBG
      scintigraphy sometimes is used to augment the CT findings. In patients with a
      nonhyperfunctioning adrenal mass, chemical shift MR and CT densitometry have
      begun to replace percutaneous adrenal biopsy or serial follow-up CT as methods to
      establish a specific diagnosis. In this article the authors review the clinical
      features and imaging findings of patients with known or suspected adrenal masses.

PMID- 9275982
TI  - Update on interventional uroradiology.
AB  - From its humble beginnings as a method of expediently decompressing the
      obstructed kidney, the field of interventional uroradiology has evolved in the
      hands of urologists and interventional radiologists to a means of addressing
      myriad problems in the urinary tract and has changed the day-to-day practice of
      urology. The foundation of interventional uroradiology is the creation of an
      appropriate entry into the urinary system. After a review of this basic
      procedure, extensions of the technique and new applications of emerging
      technology are reviewed.

PMID- 9275983
TI  - Scrotal imaging.
AB  - Scrotal ultrasonography has many indications. Evaluation of testis masses,
      hydroceles, and extratesticular structures are the most common indications. Color
      Doppler ultrasound has made assessment of scrotal blood flow possible. This
      enables the sonographer to make specific diagnoses in cases of acute scrotal
      pain. Other indications include evaluating infertile men, searching for an
      undescended testis, and evaluating the traumatized scrotum.

PMID- 9275984
TI  - Pediatric uroradiology update.
AB  - The present focus in pediatric uroradiology is a healthy reappraisal of the
      indications for and clinical use of the numerous modalities available for
      evaluating the child who has a urinary tract infection. The purpose of this
      article is to update the urologist with respect to the problems that are involved
      in discussing the diagnosis and imaging of the pediatric urinary tract infection.

PMID- 9275985
TI  - Extragenital muscular myocutaneous and fasciocutaneous flaps in urethral
      reconstruction.
AB  - Urethral strictures are fibrotic sequelae of inflammatory or traumatic injuries
      of the urethral epithelium and corpus spongiosa that result in a variety of
      obstructive lesions. To help resolve these difficult and challenging strictures,
      fistulas, and obliterative defects of the urethra, the author has borrowed many
      flaps from the ubiquitous bank of extragenital axial flaps presently in use for
      trunk and limb reconstruction, alone or in combination with free skin grafts.
      This article discusses and describes five extragenital flap techniques used in a
      variety of high-risk urethral strictures.

PMID- 9275986
TI  - Commentary--measurement of microsomal epoxide hydrolase activity in humans:
      problems and perspectives.

PMID- 9275987
TI  - Assessment of respiratory effect of air pollution: study design on general
      population samples.
AB  - The aim of this paper is to describe an epidemiological model to investigate the
      relationship between respiratory diseases and environmental air pollution. In the
      Po Delta prospective study, subjects were investigated before and after a large
      thermoelectric power plant began operating, in 1980 to 1982 and in 1988 to 1991,
      respectively. The Pisa prospective study was performed in 1986 to 1988 and in
      1991 to 1993, before and after the construction of a new expressway that
      encircles the city from the North to the Southeast. In each survey, subjects
      completed the interviewer-administered standardized CNR questionnaire on
      respiratory symptoms/diseases and risk factors, and performed lung function
      tests. In the second survey of each study, skin prick tests, total serum IgE
      determination, methacholine challenge test and biomarkers (such as sister
      chromatide exchanges, micronuclei, chromosomal abnormalities, DNA and hemoglobin
      adducts) were also performed. Concentrations of total suspended particulate and
      SO2 in both surveys were higher in urban than in rural areas, as well as
      symptom/disease prevalences and bronchial reactivity. Subgroups of subjects from
      the two samples were enrolled to perform a specific study on the acute
      respiratory effects of indoor pollution; the daily presence of symptoms and
      measurements of peak expiratory flow (PEF), daily activity pattern, and
      assessment of the indoor air quality (particulates < 2.5 mu and NO2) were
      evaluated. Higher symptom prevalences and PEF variability level were observed in
      subjects with the highest levels of NO2 or particulates, especially asthmatics.
      In conclusion, these studies represent a basis for further analyses to better
      define the relationship between respiratory health and indoor/outdoor pollutant
      levels.

PMID- 9275988
TI  - Atmospheric degradation of HFCs and HCFCs: chemistry and noxiousness.
AB  - Hydrohaloalkanes are potential alternatives to the fully halogenated compounds
      (CFCs) that are believed to be responsible for depletion of the stratospheric
      ozone. In order to establish whether hydrofluorocarbons (HFCs) and
      hydrochlorofluorocarbons (HCFCs) are actually more environmentally acceptable, it
      is extremely important to know, in addition to ODP and HGWP, their atmospheric
      degradation mechanism, tropospheric lifetime, and toxicity and noxiousness of
      their atmospheric degradation products. The primary atmospheric sink for
      hydrohaloalkanes is the reaction with hydroxyl radicals (OH), so that laboratory
      measurements or a reliable estimation of the rate constants (kOH) of these
      reactions is essential in order to assess their atmospheric lifetimes. The
      previsional models for kOH developed in our laboratory allow the estimation of
      the atmospheric lifetimes of as many as 449 halocarbons (i.e., all the
      halocarbons containing F and/or Cl with one, two, and three carbon atoms). The
      harmful character of some degradation products halogenated and oxygenated is also
      discussed.

PMID- 9275989
TI  - Nitroarenes of photochemical origin: a possible source of risk to human health.
AB  - Nitrated polynuclear aromatics (NPAH) have been recognized as mutagenic even
      without enzymatic activation. NPAH have been found in the urban air of the U.S.A.
      and Western Europe. Their detection in the atmosphere has been related mainly to
      in situ photochemical production. In this study, the ubiquity of NPAH in the air
      is presented despite their rare and scarce occurrence in emissions released by
      mobile and stationary sources. NPAH seem to effectively contribute to both the
      direct and indirect mutagenicity of air soot (in European countries more than in
      the U.S.A.). Moreover, they can be taken as a suitable index of the occurrence of
      reactive nitrogen compounds in the air.

PMID- 9275990
TI  - Biological activity of particle exhaust emissions from light-duty diesel engines.
AB  - Whole diesel exhaust has been classified recently as a probable carcinogen, and
      several genotoxicity studies have found particulate exhaust to be clearly
      mutagenic. Moreover, genotoxicity of diesel particulate is greatly influenced by
      fuel nature and type of combustion. In order to obtain an effective environmental
      pollution control, combustion processes using alternative fuels are being
      analyzed presently. The goal of this study is to determine whether the
      installation of exhaust after treatment-devices on two light-duty, exhaust gas
      recirculation (EGR) valve-equipped diesel engines (1930 cc and 2500 cc) can
      reduce the mutagenicity associated with particles collected during U.S.A. and
      European driving cycles. Another interesting object was to compare the ability of
      alternative biodiesel and conventional diesel fuels to reduce the mutagenic
      activity associated with collected particles from two light duty diesel engines
      (both 1930 cc) during the European driving cycle. SOF mutagenicity was assayed
      using the Salmonella/microsome test (TA 98 and TA 100 strains, +/- S9 fraction).
      In the first part of our study, the highest mutagenicity was revealed by TA98
      strain without enzymatic activation, suggesting a direct-acting mutagenicity
      prevalence in diesel particulate. The 2500 cc engine revealed twofold mutagenic
      activity compared with the 1930 cc engine (both EGR valve equipped), whereas an
      opposite result was found in particulate matter amount. The use of a noncatalytic
      ceramic trap produced a decrease of particle mutagenic activity in the 2500 cc
      car, whereas an enhancement in the 1930 cc engine was found. The catalytic
      converter and the electrostatic filter installed on the 2500 cc engine yielded a
      light particle amount and an SOF mutagenicity decrease. A greater engine stress
      was obtained using European driving cycles, which caused the strongest
      mutagenicity/km compared with the U.S.A. cycles. In the second part of the
      investigation, even though a small number of assays were available, exhaust
      emission generation by biodiesel fuel seemed to yield a smaller environmental
      impact than that of the referenced diesel fuel. The results point out the
      usefulness of mutagenicity testing in the research of both newer, more efficient
      automotive aftertreatment devices and less polluting fuels.

PMID- 9275991
TI  - Ozone measurements in the urban and extra-urban areas of Pisa during the summer
      of 1995.
AB  - During the Summer of 1995, atmospheric ozone concentrations were measured in five
      areas with different geographical and environmental characteristics. The five
      areas included: 1. Pisan coastline. 2. An urban area with a high volume of
      traffic. 3. A rural area away from emission sources. 4. Monte Serra (Alt. 900 m).
      5. The monitoring station within a small urban park. The aim of this study was to
      identify relationships between ozone concentrations and the different geophysical
      factors related to the designated areas, such as traffic volume, height above sea
      level, and the meteorological aspects of the Pisan coastline.

PMID- 9275992
TI  - Emission of isoprenoids by plants: their role in atmospheric chemistry, response
      to the environment, and biochemical pathways.
AB  - Plants produce and emit a wide range of compounds whose common precursor is
      isoprene. Because of their high reactivity with OH radicals and tropospheric O3,
      these compounds are relevant in atmospheric chemistry and may act as precursors
      of photochemical smog. They may also influence rural acid deposition and compete
      with methane for OH radicals, therefore indirectly influencing the global warming
      trend. Studies have been carried out at the plant physiology and plant
      biochemistry level in an attempt to measure the emission of isoprenoids by
      plants. A review of the present knowledge about the role of biogenic emission in
      atmospheric chemistry, the response of the emission to environmental factors, and
      the biochemical pathways of isoprenoid formation is presented.

PMID- 9275993
TI  - Oncogenic risk in a chemical plant: a methological approach and preliminary
      results.
AB  - One of the major problems that occupational medicine has to deal with is cancer
      risk assessment. Recent Italian legislation requires the evaluation of
      occupational exposure to carcinogens in all workplaces, but a standardized method
      to be used in the environmental and biological criteria is generally lacking. The
      objective of this report is to identify a multidisciplinary approach to the
      research on this topic. The study is based on a chemical plant that produces
      pitch. The multidisciplinary approach is based on risk- and health-damage
      assessments. Ethical aspects are also taken into account, and the research design
      incorporates an informed consent for all employees. Some preliminary results are
      available. From the environmental point of view, all parameters provide an
      airborne concentration value below threshold limit values (TLVs), but biological
      monitoring demonstrates an increased urinary excretion of 1-OH-pyrene in all
      tested subjects. In conclusion, the first objective of our study is to
      demonstrate the carcinogenic risk of employees, searching for an agreement
      between environmental analysis, biological monitoring, and health effect data. A
      close collaboration between different professions is necessary.

PMID- 9275994
TI  - Chemical analysis and biological activity of airborne particulate matter.
AB  - We examined the chemical composition of the suspended particulate matter in a
      typical, middle-sized, nonindustrial Italian town in terms of total carcinogenic
      PAH, heavy metal, and polynuclear azo-aromatic compounds. The chemical data
      relate to the biological activity of the organic extract of the particulate
      matter (mutagenicity and mice alveolar macrophage phagocytosis inhibition). The
      concentration values of benz(a)pyrene, the concentration ratios of selected
      PAH's, and the GC-MS profile of some typical samples indicate that motor vehicle
      traffic is the main pollution source. PAH concentration is significantly
      correlated with mutagenicity and a phagocytosis inhibition of up to 75% was
      observed at the highest PAH concentration. As far as the effect of meteorological
      variables on PAH concentration and mutagen-icity is concerned, a statistically
      significant inverse correlation with temperature was found.

PMID- 9275995
TI  - Mutagenicity and chemical analysis of airborne particulate matter collected in
      Pisa.
AB  - The genotoxic effects of airborne particulate samples collected from two urban
      areas during various traffic intensity levels were evaluated using the yeast
      Saccharomyces cerevisiae (D7 strain) and Salmonella typhimurium (TA98 and TA100
      strains). Standard protocols were used, in compliance with recent legislation.
      Airborne particulate data reveal that genotoxic effects were more evident in the
      samples collected in the area with intense moving traffic than in the area with
      limited traffic. Particulate, benzene, toluene, NO2, CO, and heavy metal
      determinations in these two areas show that their concentrations are related to
      the intensity of traffic.

PMID- 9275996
TI  - Airborne levels of polycyclic aromatic hydrocarbons: 32P-postlabeling DNA adducts
      and micronuclei in white blood cells from traffic police workers and urban
      residents.
AB  - An epidemiologic study on 94 traffic police officers exposed to airborne
      polycyclic aromatic hydrocarbons (PAH) and 52 age-matched urban residents working
      in confined spaces considered as referent subjects without occupational exposure
      to PAH was conducted to characterize individual exposure to benzo(a)pyrene (BaP),
      benzo(b)-, and benzo(k)fluoranthene (BbF and BkF) and the occurrence of DNA
      adducts and micronuclei in white blood cells (WBC). The study's findings
      indicated that mean concentrations of PAH in the city air were 10 to 30 times
      higher among the traffic police officers compared with referent subjects (4.55 +/
      3.44 ng/m3 and 0.15 +/- 0.30 ng/m3 of BaP among police officers and referents,
      respectively). 32P-postlabeling DNA adducts in WBC obtained from police officers
      (1.48 +/- 1.35 RAL/10(8)) were significantly higher than in referent subjects
      (1.01 +/- 0.63 RAL/10(8), P = 0.007), suggesting a possible role of exposure to
      airborne PAH in the DNA damage. The frequency of micronuclei was significantly
      increased (P = 0.02) in referent subjects (4.49 +/- 2.0% cells) compared with
      police officers (3.75 +/- 1.65% cells) due to the large proportion of females in
      the former group. Comparison of the mean micronuclei frequencies among 82 male
      police officers (3.73 +/- 1.6% cells) and referents (4.03 +/- 1.61% cells) failed
      to reveal a statistically significant difference (P = 0.38). Our findings support
      the evidence of a noxious effect of the exposure to airborne PAH found in large
      cities on the occurrence of DNA adducts in WBC, whereas there seems to be no
      effect on the cytogenetic risk assessed as micronuclei frequency.

PMID- 9275997
TI  - Environmental restoration of a TiO2 plant.
AB  - Titanium dioxide is a brilliant white, nontoxic pigment. It is used worldwide to
      obtain vivid whites, clean tints, and brillant colors in paints, lacquers,
      printing inks, plastics, rubber, floorings, paper, fibers, cosmetics, vitreous
      applications, and other industries. It can be produced through two industrial
      routes: the sulfate or the chloride process. Whatever production route is used,
      it produces effluents during the process. In the past, such effluents were freely
      discharged into the environment (air, water, land) without special care. Today,
      environmental legislation requires specific treatments and sets strict limits,
      often differing from country to country. We present a case of a TiO2 plant,
      located in central Italy (Tuscany), where several steps have been taken during
      the last 20 years concerning the effluent treatment to become one of the more
      advanced examples of total treatment in the TiO2 industry worldwide. Details are
      presented concerning the treatment systems for gaseous, liquid, and solids
      effluents.

PMID- 9275998
TI  - Air pollution and the deterioration of historic monuments.
AB  - The results of air pollution surveys conducted at two sites in the historic
      center of Rome and at two sites in Latium are summarized and illustrated. The
      objective of our study is to identify a link between the analytical data and
      brightness measurements of outdoor stone monuments in the selected areas. The
      analytical data coincide well with the characteristics of the sites with heavy
      traffic (Rome and Villa d'Este in Tivoli) when compared with the "zero level
      exposure" of the Villa Adriana.

PMID- 9275999
TI  - Lichens and moss as bioindicators and bioaccumulators in air pollution
      monitoring.
AB  - In this study, we review research conducted in the La Spezia district during
      1989, 1992, and 1994, using lichens and moss as indicators of air pollution. SO2
      pollution was examined by means of an Index of Atmospheric Purity (IAP) based on
      the frequency of epiphytic lichen within a sampling grid. Metal deposits were
      estimated using the lichen Parmelia caperata and the moss Hypnum cupressiforme as
      bioaccumulators. IAP maps show progressive air quality improvement from 1989 to
      1994. This trend correlates to a decrease in SO2 emissions during recent years
      that is attributed to the use of methane for residential heating and the closing
      of a coal-fired power plant. Metal contamination maps show that the most polluted
      area is now in the southeastern part of the gulf. The pattern of pollution
      coincides with the location of the chief pollution sources in the area. From 1989
      to 1994, the metal concentrations in lichens decreased, but metal deposits in the
      southeastern area were cause for concern. High concentrations of lead in the area
      are related to emissions from a waste incinerator and a plant that produces lead
      oxide. Epidemiological investigations reveal that the area population has the
      highest levels of lead in their blood. The use of bioindicators and
      bioaccumulators permits long-term and large-scale monitoring of environmental
      pollutant levels in full agreement with traditional methods.

PMID- 9276000
TI  - Aerobiologia 2.0: a software program for processing aeropollen data.
AB  - "Aerobiologia 2.0" is a simple computer program created to handle the pollen data
      collected every 2 hrs and daily by aerobiological monitoring stations equipped
      with Hirst-type spore traps. "Aerobiologia 2.0" runs on Windows 3.1 and is
      compatible with other programs that run on this operating system. The program was
      developed to store and process pollen data through a few straightforward
      operations. An unlimited calendar automatically calculates the day of the week.
      The pollen dictionary, which can hold up to 1216 different pollen types, may be
      modified or changed completely. Concentrations for every pollen type (in pollen
      grains/m3) are automatically recorded daily and every 2 hrs. 10-day and monthly
      sums are also calculated. The percentage of selected types, groups, or families
      of pollen collected each day, every 10 days, and monthly is quickly available.
      Pollen calendars and spectra in 24-hr, 10-day, monthly, tri-monthly, half-year,
      and yearly periods are readily produced. As soon as it is entered, the pollen
      data are saved on hard disk. A year's worth of data can be saved on a single 1.44
      M byte floppy disk. Aerobiologia 2.0 is being used successfully to process the
      aeropollen data collected at the two monitoring stations managed by our
      Palynological Laboratory.

PMID- 9276001
TI  - Effect of airborne particulate extracts on monocyte oxidative metabolism.
AB  - Alveolar macrophages lie on the air side of the alveolar-capillary barrier of the
      lung. They originate from circulating monocytes and are an important first-line
      host defense against inhaled microorganisms. In monocytes and macrophages,
      phagocytosis is associated with an increase in O2 consumption and superoxide
      anion (O2-) generation, that is, "the respiratory burst". O2- is the precursor of
      highly reactive, oxygen-derived free radicals that are used to kill potential
      pathogens. Although it is well known that airborne particulate matter inhibits
      the phagocytic activity of alveolar macrophages, very little is known about the
      effect of airborne particulate extracts on the respiratory burst. In this study,
      monocytes isolated from the peripheral blood were incubated for 2 hr at 37
      degrees C with increasing concentrations of particulate extract and then
      stimulated for 30 min with phorbol 12-myristate 13 acetate (PMA) or with Zymosan.
      The released O2- was measured by the superoxide dismutase inhibitable reduction
      of cytochrome C. The results cleary showed that, at a particulate concentration
      of 0.17 mg/mL, the production of O2- was reduced to 22% and 40% of the control
      values when the cells were stimulated with PMA and Zymosan, respectively.
      Concomitantly, there was a release of LDH in the supernatant (50% of the total),
      indicating that a large proportion of cells were damaged by the treatment with
      the environmental pollutants, and some cytosolic components were released from
      the cells. Giemsa staining of the treated monocytes revealed the presence of many
      cells with a dispersed cytosol; the nucleus, although not destroyed, had a
      different shape. It was suggested that the airborne particulate matter has a
      toxic effect that induces the disintegration of the plasma membrane. Cytosolic
      factors (proteins and coenzymes) necessary for O2- production leak from the cells
      and superoxide generation is therefore reduced. It remains to be determined
      whether this phenomenon also occurs in vivo.

PMID- 9276002
TI  - A simple method to reveal possible ras mutations in DNA of urinary sediment
      cells.
AB  - Occupational and environmental exposure to carcinogens is reported to be
      responsible for 25% of all bladder tumors. Among many genetic alterations found
      in tumor bladder cells, chromosome aberrations and mutations of some oncogenes,
      such as ras genes, are common. Studies conducted to determine the rate and type
      of ras mutations involved reported rather contrasting results. Researchers agree
      that among the three members of the ras family, only H-ras is subject to
      mutations, mostly at codon 12. The rate of these mutations is still under
      investigation, although it has been evaluated as being between 6 and 76%. Using
      various techniques, some studies have shown that when a ras mutation occurs in a
      bladder tumor, it is also present in urinary sediment cells of the same patient.
      We suggest a simple method to directly detect ras mutations at codon 12 in
      urinary sediment.

PMID- 9276003
TI  - Exposure to a 50 Hz electromagnetic field induces activation of the Epstein-Barr
      virus genome in latently infected human lymphoid cells.
AB  - The EBV genome in latently infected lymphoid cells offers an opportunity to
      follow effects on the transcriptional and translational product clearly
      distinguishable from those of the host cell genome. Exposure of Akata cells, a
      human lymphoid cell line latently infected by the EBV genome, to a 50 Hz EMF
      resulted in an increased number of cells expressing the virus early antigens.
      This finding provides additional evidence that DNA can be modulated by a magnetic
      field.

PMID- 9276004
TI  - Risk assessment of complex mixtures: some considerations on polycyclic aromatic
      hydrocarbons in urban areas.
AB  - The comparative examination of experimental and epidemiological data, together
      with risk evaluations concerning coke-oven, diesel, and gasoline motor emissions,
      as well as specific PAH fractions and single PAHs, indicates that, at least under
      risk additivity hypothesis, benzo(a)pyrene (B(a) may account for only a
      relatively small amount of the whole carcinogenic potential of PAH mixtures. This
      finding emerges from the comparison of risk evaluations of coke-oven and diesel
      emissions (based on epidemiological and/or experimental data) with risk
      evaluations of B(a)P as a single substance (based on carcinogenic bioassay data),
      as well as from the results of experimental studies evaluating the carcinogenic
      potency of motor exhaust condensates, of specific condensate fractions
      (particularly, the 4-7 ring PAH fraction), and of B(a)P. These data indicate that
      B(a)P might account for a percentage of the whole mixture carcinogenic response,
      at least in the hypothesis of an additive effect of PAHs. However, the overall
      carcinogenic response and risk still appear at least approximately related to the
      B(a)P concentration in the examined PAH mixtures. Finally, recent findings on PAH
      relative potencies (compared with B(a)P potency) indicate that several PAH
      present in mixtures commonly detected in occupational and in the general
      environment are characterized by a carcinogenic potency comparable with or even
      higher than that of B(a)P. This confirms the above hypothesis with respect to the
      significant, but minor role, of B(a)P. This relatively coherent picture appears
      to confirm that the reference to B(a)P as a complex mixture index may still
      represent a reasonable solution. However, the selection of a few other indicators
      from among the PAH whose relative concentrations and relative carcinogenic
      potencies are higher might improve the analysis.

PMID- 9276005
TI  - Immune response prevalence to formaldehyde-human serum albumin molecular adduct
      in a healthy population.
AB  - Formaldehyde (F) covalently binds human serum albumin (HSA), giving rise to the
      molecular adduct, F-HSA, with F as a hapten. Humoral immune response to the
      adduct provides a biological marker of F exposure. A new indirect competitive
      enzyme immunoassay (displacement assay) using an in vitro conjugate F-HSA adduct
      with a 10:1 ratio was developed to titrate serum anti-F-HSA antibodies. 219
      healthy subjects were examined using this assay. Examination of the data using
      multivariate regression analysis revealed a significant association between the F
      exposure marker and smoking variables in both smokers (p < 0.001) and ex-smokers
      (p < 0.01). No association was found between F exposure marker values and age,
      sex, residence, or profession. Except for the fact that the smoking variable
      subdivided the population into smokers, ex-smokers, and non-smokers, a
      significant association was found in non-smokers concerning professional exposure
      (p < 0.03). Results confirm that the Displacement Assay (sensitivity 96% and
      specificity 71%) is a useful method of evaluating F exposure, especially in large
      scale public health monitoring. In order to evaluate the importance of other
      exposure sources, such as F pollution in indoor and outdoor air, an interesting
      follow up to our study would be an evaluation of a possible increase of anti-F
      HSA immune response in non-smokers.

PMID- 9276006
TI  - Chemical characterization of the PM10 fraction of airborne particulate matter in
      the urban atmosphere.
AB  - This study examines the chemical composition of PM10, the thoracic fraction of
      atmospheric particulate matter. This fraction is characterized by a very complex
      composition and is able to penetrate the human organism corresponding to a "cut
      point" at the level of the larynx. We used a sampling device to separate the PM10
      from other fractions with different aerodynamic behavior. The high volume sampler
      collected large amounts of material, making it easier to study the
      micropollutants. Furthermore, it met EPA performance specifications for the
      measurement of suspended PM10 fraction. We collected the samples during different
      metereological conditions in the urban area of the town of Leghorn in Tuscany,
      Italy. Two sites, characterized by different settings, were chosen in the city.
      Both sites were marked by intense motor vehicle traffic. A better chemical
      characterization of the collected material became possible using different
      analytical techniques. The use of large-size cellulose or glass fiber filters
      allowed us to subdivide the sample and to submit each portion to a different
      investigative technique. The PAH content of the PM10 fraction was examined,
      particularly for those compounds of toxicological interest. The concentrations of
      the compounds were evaluated by HPLC with diode array UV detection. We further
      determined the contents of various heavy metals from anthropic or telluric
      sources (Pb, Cu, Fe, Cr, Cd, Mn, V, and Ni) by means of an HGA Graphite Furnace
      AAS-Zeeman-Effect technique or AA-Flame spectrophotometry. The results of our
      experiment show that motor vehicle traffic is the prevailing pollution source.
      The metereological conditions also play a significant role. The samples taken
      closer to the industrial area of the town showed a slightly higher mean content
      of PM10 fraction. The concentrations of both heavy metals and PM10 were lower
      compared with equivalent data from other European cities.

PMID- 9276007
TI  - A study of airborne Ulmaceae pollen in Modena (northern Italy).
AB  - We examined Ulmaceae airborne pollen at the Modena-Geophysical Observatory
      monitoring station in 1993. The pollen trap was placed 15 m above the ground. 365
      daily slides were fully analyzed to obtain daily and bi-hourly pollen
      concentrations. Morphological analysis on native and introduced Ulmaceae pollen
      was also conducted between February 3rd and May 17th. Five pollen types were
      identified: Celtis cf. australis, Ulmus glabra, Ulmus cf. laevis, Ulmus cf.
      minor, and Ulmus minor/laevis. Pollen concentrations and percentages showed that
      the Elm family contributed little pollen to the air (about 1% of the total pollen
      recorded), Ulmus and Celtis being 0.9% and 0.04%, respectively. The maximum
      levels were 30 p/m3/24 hr and 118 p/m3/ 2 hr (Ulmus) and 4 p/m3/24 hr and 13
      p/m3/2 hr (Celtis). The highest levels of Ulmus were during the morning and
      afternoon, while the afternoon was highest for Celtis. In general, Ulmaceae trees
      appear worth planting in urban areas, but Celtis pollen should also be monitored
      at human height.

PMID- 9276008
TI  - A database for evaluating the toxicological risk of pesticides.
AB  - This study of Overtox-DB, a computerized database for managing chemical toxicity
      data, is a product of the application of typical methodologies regarding
      information science and computer technology. The methodology applied can be
      reduced to three-basic elements: the collection of requirements, design, and
      achievement. Overtox-DB was developed by defining technological elements for
      managing data and its structure and by identifing the procedures and
      methodologies for data storage, retrieval, distribution, and standardization of
      many kinds of test data stored in the same format. The program stores data about
      chemical identification, physical and chemical properties, toxicological tests,
      mutagenicity, teratogenicity, carcinogenicity, and a bibliography of chemical
      compounds. Overtox-DB consists of five modules: experimental and bibliographic,
      data collection, molecular data collection, data search, and data report. The
      Overtox-DB user responds to a simplified set of query commands and boolean
      operators that interact with the system to retrieve different toxicological data
      (the majority of fields are defined as search fields and identify the test
      system, results of the assays, administration route, dose, etc.). The collected
      information provides an analytical characterization of biological activities for
      many compounds and identifies evidence possibly lacking in experimental
      approaches. Indeed, this database could permit a comparative evaluation with
      other substances and can be used for structure-activity relationship studies.

PMID- 9276009
TI  - Mt. Cimone Observatory: baseline station for the measurement of gaseous
      substances and radioactive tracers in the atmosphere.
AB  - An extensive research program to record atmospheric physicochemical parameters
      and to track climatological trends was established at a remote Alpine station at
      Mt. Cimone Observatory in Italy. The main features of the study are outlined
      briefly and the results thus far collected, including surface ozone, carbon
      dioxide, stratospheric NO2 and O3, and airborne radioactivity are provided.

PMID- 9276010
TI  - Atmospheric pollution originating from the interaction of different gaseous
      effluents.
AB  - During the last few years, several episodes of atmospheric pollution have been
      reported in a limited area near Guidonia, Rome. The area contains a disposal
      plant, Inviolata, for the collection of municipal solid waste (MSW) and a famous
      thermal water resort, the Acque Albule spring, which is a source of water rich in
      H2S. We conducted a multiparametric study in the areas surrounding the solid
      waste disposal plant and the Acque Albule spring. The concentration of main
      gaseous effluent was continuously monitored over a period of 4 months and the
      data relating to the meteorologic conditions in the area during the last few
      decades were examined. Our results suggest that most of the atmospheric pollution
      is due to the interaction of different gaseous effluents. Specifically, the
      presence of relatively high levels of hydrogen sulfide in the atmosphere,
      constantly released in large amounts by the Acque Albule springs, and of biogases
      (mainly hydrocarbons) from the organic matter present in the solid waste
      continuously unloaded and stored at the disposal plant, lead to mixing and
      photochemical interactions between these chemical compounds, which in turn are
      responsible for most of the polluting effects. Such interactions are promoted by
      the strong solar irradiation in the area that is enhanced by the peculiar local
      meteorological features that do not allow the pollutants to disperse.

PMID- 9276011
TI  - A new fast and standardless method for direct determination of metals associated
      with particulate matter in air: avoiding errors in the determination of Pb in an
      urban environment.
AB  - We describe a new method and the relevant instrumentation necessary for its
      implementation in the analysis of metals associated with particulate matter in
      air. The procedure can be divided into two steps: in the first step the sample is
      accumulated in a device through electrostatic precipitation whose center is a
      graphite tube; in the second step the graphite tube itself is used as an
      atomization device for the determination of the metals present in the sample
      through the electrothermal atomic absorption technique. The method is simple,
      fast, accurate, and inexpensive. Moreover, if the experimental conditions are
      well chosen, there is no need for calibration, which is very convenient in the
      case of samples such as particulate matter in the air. The elements that can be
      determined with the present apparatus are Hg, Cd, Tl, Ag, Mg, and Mn. These are
      highly or medium volatile because the materials used cannot reach very high
      temperatures for long periods. The experiments are confined to air, but other
      gases, in which a corona discharge is possible, would give the same results. With
      the method proposed, it was possible to show that the official method for Pb
      determination in the urban environment of Bologna presents a negative systematic
      error of about 25%.

PMID- 9276012
TI  - 2-Carbomethoxy-3-aryl-8-oxabicyclo[3.2.1]octanes: potent non-nitrogen inhibitors
      of monoamine transporters.
AB  - Cocaine is a potent stimulant of the mammalian central nervous system. Its
      reinforcing and stimulant properties have been associated with its propensity to
      bind to monoamine transporter systems. It has generally been assumed that the
      amino function on monoamines is a requirement for binding to monoamine
      transporters. In particular, the 8-amino function on the tropane skeleton of
      cocaine and cocaine analogs has been assumed to provide an ionic bond to the
      aspartic acid residue on the dopamine transporter (DAT). We have prepared the
      first 8-oxa analogs of the 3-aryltropanes (WIN compounds) and have found that the
      3 beta-(3,4-dichlorophenyl) (6g) and 3 alpha-(3,4-dichlorophenyl) (7g) analogs
      are particularly potent (IC50 = 3.27 and 2.34 nM, respectively) inhibitors of the
      dopamine transporter. We now describe the synthesis and biology of the family of
      2-carbomethoxy-3-aryl-8-oxabicyclo[3.2.1]octanes and demonstrate that an amino
      nitrogen is not required for binding to the DAT.

PMID- 9276013
TI  - N-arylpiperazinyl-N'-propylamino derivatives of heteroaryl amides as functional
      uroselective alpha 1-adrenoceptor antagonists.
AB  - Novel arylpiperazines were identified as alpha 1-adrenoceptor (AR) subtype
      selective antagonists by functional in vitro screening. 3-[4-(ortho-Substituted
      phenyl)piperazin-1-yl]propylamines were derivatized with N,N-dimethyl
      anthranilamides, nicotinamides, as well as carboxamides of quinoline, 1,8
      naphthyridine, pyrazolo[3,4-b]pyridine, isoxazolo[3,4-b]pyridine, imidazo[4,5
      b]pyridine, and pyrazolo[1,5-a]pyrimidines. Strips of rabbit bladder neck were
      employed as a predictive assay for antagonism in the human lower tract. Rings of
      rat aorta were used as a "negative screen" for the test antagonists. Binding to
      alpha 1-ARs was relatively sensitive to size and electronic features of the
      arylpiperazine portion of the antagonists and permissive to these features on the
      heteroaryl carboxamide side. These structure-affinity findings were exploited to
      produce nicotinamides (e.g. 13ii and 25x) and pyrazolo[3,4-b]pyridines (e.g. 37f
      and 37y) ligands with nanomolar affinity at the alpha 1-AR subtype prevalent in
      the human lower urinary tract(pA2 values: 8.8, 10.7, 9.3, and 9.9, respectively)
      and displaying 2-3 orders of magnitude selectivity over the alpha 1D-AR.

PMID- 9276014
TI  - Chromeno[3,4-c]pyridin-5-ones: selective human dopamine D4 receptor antagonists
      as potential antipsychotic agents.
AB  - The discovery of a series of chromeno[3,4-c]pyridin-5-ones with selective
      affinity for the dopamine D4 receptor is described. Target compounds were tested
      for binding to cloned human dopamine D2, D3, and D4 receptor subtypes expressed
      in Chinese hamster ovary (CHO) K-1 cells. Several compounds demonstrated single
      digit nanomolar Ki values for binding to the D4 receptor with several hundred
      fold selectivities toward the D2 and D3 receptors. A limited SAR study of this
      series is discussed. In a mitogenesis assay measuring [3H]thymidine uptake, the
      target compounds showed antagonist to weak partial agonist activity at the D4
      receptor, with intrinsic activities ranging from 0 to 35%. Compound 6, 3-benzyl-8
      methyl-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one, increased DOPA (L-3,4
      dihydroxyphenylalanine) synthesis 84% in the hippocampus and 10% in the striatum
      of rat brain when dosed orally at 10 mg/kg.

PMID- 9276015
TI  - Synthesis, biological evaluation, and structure-activity relationships of 3
      acylindole-2-carboxylic acids as inhibitors of the cytosolic phospholipase A2.
AB  - 3-Acylindole-2-carboxylic acid derivatives were prepared and evaluated for their
      ability to inhibit the cytosolic phospholipase A2 of intact bovine platelets. To
      define the structural requirements for enzyme inhibition, the carboxylic acid
      group, the acyl residue, and the moiety in position 1 were systematically
      modified. Furthermore, different substituents were introduced into the phenyl
      part of the indole. Replacement of the carboxylic acid group in position 2 of the
      indole with an acetic or propionic acid substituent led to a decrease of
      inhibitory potency. Enzyme inhibition was optimal when the acyl residue in
      position 3 had a length of 12 or more carbons. Conformational restriction of the
      acyl residue did not influence activity. Introduction of alkyl chains at position
      1 of the indole with 8 or more carbons resulted in a loss of activity. However,
      replacing the omega-methyl group of such compounds with a carboxylic acid moiety
      was found to increase inhibitory potency significantly. Among the tested indole
      derivatives, 1-[2-(4-carboxyphenoxy)ethyl]-3-dodecanoylindole-2-carboxyli c acid
      (29b) had the highest potency. With an IC50 of 0.5 microM it was about 20-fold
      more active than the standard cPLA2 inhibitor arachidonyl trifluoromethyl ketone
      (IC50: 11 microM).

PMID- 9276016
TI  - Optimization of 3-(1H-indazol-3-ylmethyl)-1,5-benzodiazepines as potent, orally
      active CCK-A agonists.
AB  - We previously described a series of 3-(1H-indazol-3-ylmethyl)-1,5-benzodiazepine
      CCK-A agonists exemplified by compound 1 (GW 5823), which is the first reported
      binding selective CCK-A full agonist demonstrating oral efficacy in a rat feeding
      model. In this report we describe analogs of compound 1 designed to explore
      changes to the C3 and N1 pharmacophores and their effect on agonist activity and
      receptor selectivity. Agonist efficacy in this series was affected by
      stereoelectronic factors within the C3 moiety. Binding affinity for the CCK-A vs
      CCK-B receptor showed little dependence on the structure of the C3 moiety but was
      affected by the nature of the second substituent at C3. Structure-activity
      relationships at the N1-anilidoacetamide "trigger" moiety within the C3 indazole
      series were also investigated. Both agonist efficacy and binding affinity within
      this series were modulated by variation of substituents on the N1
      anilidoacetamide moiety. Evaluation of several analogs in an vivo mouse
      gallbladder emptying assay revealed compound 1 to be the most potent and
      efficacious of all the analogs tested. The pharmacokinetic and pharmacodynamic
      profile of 1 in rats is also discussed.

PMID- 9276017
TI  - Synthesis and antimalarial effects of phenothiazine inhibitors of a Plasmodium
      falciparum cysteine protease.
AB  - Acridinediones have previously been shown to have potent antimalarial activity. A
      series of sulfur isosteres of acridinediones have been synthesized and evaluated
      for their inhibition of the Plasmodium falciparum cysteine protease falcipain and
      for their antimalarial activity. A number of these phenothiazines inhibited
      falcipain and demonstrated activity against cultured P. falciparum parasites at
      low micromolar concentrations. We propose that the compounds exerted their
      antimalarial effects by two mechanisms, one of which involves the inhibition of
      falcipain and a consequent block in parasite degradation of hemoglobin. These
      compounds and related phenothiazines are worthy of further study as potential
      antimalarial agents.

PMID- 9276019
TI  - beta-Methylation of the Phe7 and Trp9 melanotropin side chain pharmacophores
      affects ligand-receptor interactions and prolonged biological activity.
AB  - Topographically modified melanotropin side chain pharmacophore residues Phe7 and
      Trp9 in a cyclic peptide template (Ac-Nle4-c[Asp-His-Xaa7-Arg-Yaa9-Lys]-NH2) and
      Phe7 in a linear peptide template (Ac-Ser-Tyr-Ser-Nle4-Glu-His-Xaa7-Arg-Trp-Gly
      Lys-Pro-Val-NH2) result in differences in potency and prolonged biological
      activity in the frog and lizard skin bioassays. These topographic modifications
      included the four isomers of beta-methylphenylalanine (beta-MePhe)7 and beta
      methyltryptophan (beta-MeTrp)9 and the two isomers of 1,2,3,4-tetrahydro-beta
      carboline (Tca)9 Modifications in the cyclic template resulted in up to a 1000
      fold difference in potency for the beta-MePhe7 stereoisomeric peptides; up to a
      476-fold difference in potency resulted for the beta-MeTrp9 peptides, and about a
      50-fold difference between the Tca9-containing peptides. Up to a 40-fold
      difference in potency resulted for the beta-MePhe7 stereoisomeric peptides using
      the linear template in these assays. The relative potency ranking for
      modifications in the cyclic template of beta-MePhe7 were 2R,3S > 2S,3S = 2S,3R >
      2R,3R in the frog assay and 2S,3R > 2R,3S > 2S,3S > 2R,3R in the lizard assay.
      The relative potencies for modifications in the cyclic template of beta-MeTrp9
      were 2R,3S > 2R,3R > 2S,3S > > 2S,3R in the frog assay and 2S,3S = 2R,3R > 2R,3S
      > 2S,3R in the lizard assay. The relative potencies for modifications in the
      cyclic template of Tca9 were DTca > LTca in both assays. Significant differences
      in prolonged (residual) activities were also observed for these modified peptides
      and were dependent upon stereochemistry of the beta-methyl amino acid, peptide
      template, and bioassay system. Furthermore, comparisons of beta-MeTrp9
      stereoisomeric peptides on the frog, lizard, and human MC1 receptors suggest that
      structure-activity relationships on both the classical frog and lizard skin
      bioassays do not necessarily predict corresponding SAR profiles for the human
      melanocortin receptors, indicating a remarkable species specificity of the MC1
      receptor requirements.

PMID- 9276020
TI  - Synthesis and anti-hepatitis B virus activity of 9-(2-deoxy-2-fluoro-beta-L
      arabinofuranosyl) purine nucleosides.
AB  - Since the discovery of 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil (L-FMAU)
      as a potent anti-HBV and anti-EBV agent, we have studied the structure-activity
      relationships of 2'-deoxy-2'-fluoro-beta-L-arabinofuranosylpyrimidine nucleosides
      as anti-HBV agents. Therefore it is rational to extend this study to the purine
      nucleosides. Thus, 3,5-di-O-benzoyl-2-deoxy-2-fluoro-beta-L-arabinofuranosyl
      bromide (1), which was prepared from L-xylose via a multistep procedure, was
      coupled with several purines by the sodium salt method. From this general
      synthesis, 10 purine nucleosides containing the 2-deoxy-2-fluoro-beta-L
      arabinofuranosyl moiety have been obtained. The anti-HBV activity and toxicity of
      the synthesized nucleosides were evaluated in HepG2 2.2.15 cells. Among them, the
      adenine (10) and hypoxanthine (15) derivatives exhibit good in vitro anti-HBV
      activity (EC50 = 1.5 and 8 microM, respectively) without significant toxicity up
      to 200 microM.

PMID- 9276018
TI  - Synthesis and opioid activity of [D-Pro10]dynorphin A-(1-11) analogues with N
      terminal alkyl substitution.
AB  - Several N-terminal di- and monoalkylated derivatives of [D-Pro10]dynorphin A-(1
      11) were synthesized in order to explore the structure-activity relationships for
      antagonist vs agonist activity at kappa-opioid receptors. N,N-Dialkylated and N
      monoalkylated (alkyl = allyl, benzyl, and cyclopropylmethyl (CPM) tyrosine
      derivatives were prepared from tyrosine tert-butyl ester and the corresponding
      alkyl halides. [D-Pro10]Dyn A-(2-11) was prepared by solid phase synthesis using
      Fmoc-protected amino acids, and the tyrosine derivatives were coupled to the
      peptide with BOP ((benzotriazol-1-yloxy)tris(dimethylamino)phosphonium
      hexafluorophosphate). Both the degree of substitution and the identity of the
      alkyl group affected kappa-receptor affinity, selectivity, and efficacy. All of
      the N-monoalkylated derivatives exhibited much higher affinity (Ki < 0.05 nM) for
      kappa receptors in the guinea pig cerebellum and greatly enhanced kappa-receptor
      selectivity (Ki ratio (kappa/mu) > 200) compared to the N,N-dialkyl [D-Pro10]Dyn
      A-(1-11) analogues, although one disubstituted analogue, N,N-diCPM[D-Pro10]Dyn A
      (1-11), retained high affinity (Ki = 0.19 nM) for kappa receptors. Thus the
      introduction of the second alkyl group at the N-terminus lowered kappa-receptor
      affinity and selectivity. The N-allyl and N-CPM analogues were moderately potent
      agonists in the guinea pig ileum (GPI) assay, while the N-benzyl derivative was a
      weak agonist in this assay. In vivo in the phenylquinone abdominal stretching
      assay the N-CPM analogue exhibited potent antinociceptive activity (ED50 = 1.1
      micrograms/mouse), while N-allyl[D-Pro10]Dyn A-(1-11) exhibited weak
      antinociceptive activity (ED50 = 27 micrograms/mouse). For the N,N-dialkyl
      derivatives the identity of the N-terminal alkyl group affected the efficacy
      observed in the smooth muscle assays. The N,N-diCPM analogue exhibited negligible
      agonist activity, and N,N-diallyl[D-Pro10]Dyn A-(1-11) showed weak antagonist
      activity against Dyn A-(1-13)NH2 in the GPI. In contrast, the N,N-dibenzyl
      compound showed appreciable opioid agonist activity in this assay. In vivo the
      N,N-diallyl analogue exhibited weak antinociceptive activity (ED50 = 26
      micrograms/mouse in the phenylquinone abdominal stretching assay). The N
      monoalkylated peptides are among the most kappa-selective opioid peptides
      reported to date, showing comparable or greater selectivity and higher affinity
      than the kappa-selective non-peptide agonists U-50,488 and U-69,593. The N,N
      diCPM and N,N-diallyl peptides are lead compounds in the development of peptide
      based kappa-receptor antagonists.

PMID- 9276021
TI  - 6A-O-[(4-biphenylyl)acetyl]-alpha-, -beta-, and -gamma-cyclodextrins and 6A-deoxy
      6A-[[(4-biphenylyl)acetyl]amino]-alpha-, -beta-, and -gamma-cyclodextrins:
      potential prodrugs for colon-specific delivery.
AB  - Cyclodextrins (CyDs) are known to be fermented to small saccharides by colonic
      microflora, whereas they are only slightly hydrolyzable and thus are not easily
      absorbed in the stomach and small intestine. This property of CyDs is
      particularly useful for colon-specific delivery of drugs. In this study, an
      antiinflammatory 4-biphenylylacetic acid (BPAA) was selectively conjugated onto
      one of the primary hydroxyl groups of alpha-, beta-, and gamma-CyDs through an
      ester or amide linkage, 6A-O-[(4-biphenylyl)acetyl[-alpha-, -beta-, and -gamma
      CyDs (1-3) and 6A-deoxy-6A-[[(4-biphenylyl)acetyl]amino]-alpha-, -beta-, and 
      gamma-CyDs (4-6). In rat cecal and colonic contents (10%, w/v), 1 and 3 released
      more than 95% of BPAA within 1-2 h, and 2 released about 50% of the drug within
      12 h. The amide prodrugs, 4-6, did not release BPAA in the cecal contents, but
      gave BPAA/maltose or BPAA/triose conjugates linked through an amide bond. On the
      other hand, these prodrugs were found to be stable in the contents of rat
      stomachs and small intestines, in intestinal or liver homogenates, and in rat
      blood. The serum levels of BPAA increased about 3 h after oral administration of
      1 and 3 to rats, accompanying a marked increase in the serum levels, whereas 2
      and 4-6 resulted in little increase of the serum levels. These facts suggest that
      BPAA is released after the ring opening of CyDs followed by the ester hydrolysis,
      and the BPAA activation takes place site-specifically in the cecum and colon.
      Therefore, the present CyD prodrug approach provides a versatile means of
      constructing a novel colon-specific drug delivery system.

PMID- 9276022
TI  - Novel agonists of 5HT2C receptors. Synthesis and biological evaluation of
      substituted 2-(indol-1-yl)-1-methylethylamines and 2-(indeno[1,2-b]pyrrol-1-yl)-1
      methylethylamines. Improved therapeutics for obsessive compulsive disorder.
AB  - The syntheses of a series of substituted 2-(indol-1-yl)-1-methylethylamines and 2
      (indeno[1,2- b]pyrrol-1-yl)-1-methylethylamines are reported. The binding
      affinities of the compounds at 5HT2C and 5HT2A receptors (79% homology in the
      transmembrane domain) were determined. The ligands displayed selectivity for
      5HT2C receptors relative to 5HT2A receptors. Compounds were functionally
      characterized both in vitro and in vivo as 5HT2C receptor agonists. 5f, 5l, 5n,
      5o, 5q, 14c, 14f, 14k, and 14m exhibited anticompulsive activity in an animal
      model of obsessive compulsive disorder.

PMID- 9276023
TI  - Synthesis, photophysical properties, in vivo photosensitizing efficacy, and human
      serum albumin binding properties of some novel bacteriochlorins.
AB  - The synthesis, photophysical characteristics, in vivo photosensitizing efficacy,
      human serum albumin (HSA) binding properties, and skin phototoxicity of some
      stable bacteriochlorins were investigated. The novel bacteriochlorins, obtained
      from chlorophyll-a, have long-wavelength absorptions in the range lambda max =
      734-758 nm. Preferential migration of ethyl over methyl substituents among
      ketobacteriochlorins obtained in the pinacol-pinacolone rearrangements of vic
      dihydroxybacteriochlorins was confirmed by NOE studies. The bacteriochlorins show
      relatively low fluorescence quantum yields. Among all the bacteriochlorins the
      triplet states were quenched by ground state molecular oxygen in a relatively
      similar manner, yielding comparable singlet oxygen quantum yields. In preliminary
      in vivo studies (DBA/2 mice, transplanted with SMT/F tumors),
      ketobacteriochlorins were found to be more photodynamically active than the
      related vic-dihydroxy analogues. Replacement of the methyl ester functionalities
      with di-tert-butylaspartic acids enhanced the in vivo efficacy. Site specific
      human serum albumin (HSA) binding studies indicated a direct correlation between
      the ability of the compound to bind to the diazepam binding site (albumin site
      II) and the in vivo photosensitizing efficacy.

PMID- 9276024
TI  - Antipsoriatic anthrones with modulated redox properties. 4. Synthesis and
      biological activity of novel 9,10-dihydro-1,8-dihydroxy-9-oxo-2
      anthracenecarboxylic and -hydroxamic acids.
AB  - A novel series of carboxylic and hydroxamic acids based on 1,8-dihydroxy-9(10H)
      anthracenone were synthesized from 8-hydroxy-1-methoxy-9,10-anthracenedione as
      the key intermediate and evaluated both in the bovine polymorphonuclear leukocyte
      5-lipoxygenase (5-LO) assay and in the HaCaT keratinocyte proliferation assay for
      their enzyme inhibitory and antiproliferative activity, respectively. The most
      potent inhibitors in both assays were the N-methylated hydroxamic acids 5d-8d
      with straight chain alkyl spacers. Incorporation of these structural features on
      the anthracenone pharmacophore resulted in increased inhibitory activity against
      5-LO while the antiproliferative activity was retained. In addition, prooxidant
      properties as measured by deoxyribose degradation and cytotoxicity as assessed by
      LDH release were largely reduced as compared with the antipsoriatic anthralin.
      Contrary to anthralin, antioxidant properties were observed as documented by the
      reactivity of the novel compounds against free radicals and inhibition of lipid
      peroxidation in model membranes.

PMID- 9276025
TI  - Immunologically specific activation of a cephalosporin derivative of mitomycin C
      by monoclonal antibody beta-lactamase conjugates.
AB  - The syntheses of two cephalosporin derivatives 2 and 3 of mitomycin C (1)
      containing 7-phenylacetamido and 7-delta-carboxybutanamido side chains,
      respectively, are described. These compounds were prepared for evaluation as
      cephalosporin prodrugs capable of being activated by mAb-beta-lactamase
      conjugates. In vitro cytotoxicity assays performed on H2987 lung adenocarcinoma
      and clone 62 melanoma cell lines indicated that compound 2 was comparable in
      cytotoxicity to the parent drug. In an effort to improve upon the cytotoxic
      differential of 2, an alternative prodrug 3 containing a polar carboxyl group in
      the side chain of the cephalosporin moiety was prepared. Compound 3 consistently
      behaved as a prodrug and was approximately 40- and 10-fold less toxic than 1
      toward H2987 and clone 62, respectively. Determination of kinetic constants for
      hydrolysis by beta-lactamase from Enterobacter cloacae P99 indicated kcat values
      of 476 +/- 170 and 248 +/- 15.1 s-1 for 2 and 3, respectively. The kcat/Km ratios
      for 2 and 3 were found to be approximately 9.7 and 2.1 microM/s, respectively.
      Comparison of these kcat/Km values with those obtained for similar cephalosporin
      derivatives of other antitumor agents demonstrated that compounds with delta
      carboxybutanamido side chains generally have slightly diminished efficiency of
      enzymatic hydrolysis compared to the corresponding 7-phenylacetamido analog. It
      was also demonstrated that the less toxic prodrug 3 was activated in an
      immunologically specific manner by L6-F(ab')-beta-lactamase and 96.5-F(ab')-beta
      lactamase conjugates, selective for H2987 and clone 62 cells, respectively.

PMID- 9276026
TI  - Induction of apoptosis in human hepatoma cells by alpha-fetoprotein.
AB  - We have investigated the effects of purified human alpha-fetoprotein (AFP) on the
      growth of the human hepatocarcinoma-cells HepG2 in culture. Cancer-derived AFP
      (cAFP), isolated from the culture medium of AFP-secreting HepG2 cells and
      embryonal AFP (eAFP), isolated from human cord serum, were used for these
      studies. Both AFP pre parations studied were shown to induce strong dose
      dependent inhibition of HepG2 cell proliferation and complete growth arrest at
      high protein concentrations (more than 0.1 mg/ml). To test whether AFP may
      trigger an endogenous suicide program in hepatoma cells, we examined whether DNA
      fragmentation preceded cell death. After exposure of the cells of the high AFP
      dose (1.0 mg/ml), DNA fragmentation was detected as early as 2 h after treatment,
      and 70% of cells were apoptotic by 24 h. DNA fragmentation was shown to precede
      other signs of cell death for several hours. Typical morphological changes of
      apoptosis were observed after 4 h of exposure of cells to high AFP doses. Low
      concentrations of cAFP and eAFP (less than 0.1 mg/ml) failed to induce growth
      inhibition of HepG2 cells, rather showing a weak stimulative effect,
      demonstrating a biphasic AFP activity. Cell pretreatment with the transcriptional
      inhibitor actinomycin D had no measurable influence on AFP cytotoxicity. These
      findings demonstrate that protein synthesis is not required for this mechanism of
      cell death. The charcoal-treated ligand-free eAFP (eAFPp) had a dose-dependent
      growth-inhibitory activity, similar to intact protein, but slightly less
      intensive. The similar growth-inhibitory activities of cAFP, eAFP and eAFPp,
      which have a significant difference in bound-ligand content, provide evidence
      that the main role in cell growth regulation may be attributed to the protein
      moiety of the entire AFP molecule, but not to its ligands. These biologically
      active AFP ligands could, however, modulate AFP-growth-regulating activity.
      Growth factor deprivation distinctly enhanced the cytostatic activity of high AFP
      concentrations and also increased the mitogenic activity of low AFP levels,
      showing the interdependence of the growth-regulative activity of AFP and growth
      factors. The findings of this study demonstrated that AFP is directly introduced
      into the intracellular pathways of cell growth regulation and programmed cell
      death.

PMID- 9276027
TI  - Stability of human urinary gonadotropin peptide.
AB  - In this report, we evaluate the stability of urinary gonadotropin peptide (UGP),
      an urinary tumor marker for trophoblastic malignancies, which is also promising
      for other types of cancer. The concentrations were independent of the duration of
      storage (p > 0.1), but the mean difference between UGP values for samples stored
      at 4 degrees C and those kept at room temperature is 5.5% (p < 0.002), with the
      higher values for refrigerated samples. We conclude that UGP is stable at room
      temperature, allowing mailing of urine samples. Refrigerated (4 degrees C)
      samples show slightly increased values. However, this will have no clinical
      relevance in monitoring cancer patients.

PMID- 9276028
TI  - CA125 phosphorylation is associated with its secretion from the WISH human amnion
      cell line.
AB  - Evidence is presented suggesting that CA125 is a serine and/or threonine
      phosphoprotein and that its secretion from the human amnion WISH cell line is
      closely linked to its phosphorylation. It is also indicated that regulation of
      CA125 secretion requires protein(s) tyrosine phosphorylation. WISH cells treated
      with a tyrosine phosphatase inhibitor, vanadate/ H2O2, resulted in increased
      levels of CA125 secretion. Exposure of vanadate-treated cells to epidermal growth
      factor further enhanced this secretory activity. Immunohistochemistry of vanadate
      treated cells resulted in a substantial increase in not only cytoplasmic tyrosine
      phosphoproteins but also in membrane-associated CA125 when stained with the PY20
      anti-phosphotyrosine and M11 anti-CA125 monoclonal antibodies, respectively. M11
      immunoprecipitation of CA125 from cells labelled with [32P]-orthophosphate was
      analyzed by SDS-PAGE and autoradiography. Immunoprecipitates from cell lysates
      demonstrated that a phosphoprotein of > 200 kD was isolated and immunoreacted
      with both the OC125 and M11 anti-CA125 monoclonal antibodies by Western blotting.
      CA125 immunoprecipitated from vanadate-treated cells showed a marked increase in
      cell-associated CA125 phosphorylation. Although CA125 could be immunoprecipitated
      from WISH cell media incubated with [32P]-orthophosphate in the presence or
      absence of vanadate as detected by Western blotting, autoradiographic analysis of
      the Western blots revealed no [32P]-labelled CA125 co-migrating with the 200-kD
      plus molecule detected by M11. When the PY20 anti-phosphotyrosine monoclonal
      antibody was used as the probe, no tyrosine-phosphorylated CA125 was detected in
      cell lysates.

PMID- 9276029
TI  - Cytoplasmic localization of endothelial constitutive nitric oxide synthase in
      endometrial carcinomas.
AB  - BACKGROUND: Production of nitric oxide by nitric oxide synthase (NOS) has been
      implicated in numerous physiologic and pathophysiologic processes including
      mutagenesis. This study was designed to examine the expression of the endothelial
      constitutive isoform of NOS (ecNOS) in endometrial carcinomas. METHODS: Fifty
      endometrial carcinomas (42 endometrioid, 4 serous papillary, 2 clear cell, and 2
      adenosquamous carcinomas) and 21 normal endometrial gland tissue specimens (5
      cases of proliferative, 5 early secretory, 5 mid-secretory, and 5 late secretory
      and 1 menstrual phase endometrium), previously formalin fixed and paraffin
      embedded, were immunostained using a commercially available anti-ecNOS monoclonal
      antibody. Localization of ecNOS staining to the plasma membrane, cytoplasm and
      nuclei was graded with respect to overall staining intensity (0-3+ scale) and
      frequency (percentage of immunoreactive cells). RESULTS: Relatively little
      staining for ecNOS was localized to the plasma membrane in either normal or
      neoplastic tissues. Normal and hyperplastic endometrial glands demonstrated
      moderate cytoplasmic and weak nuclear staining in a small percentage of cells.
      While ecNOS expression was most prominent in epithelial cells, weak expression
      was also rarely noted in endometrial stroma, blood vessel walls, and endothelium.
      We found a broad range of ecNOS expression in endometrial carcinomas,
      predominantly localized to the cytoplasm and nuclei. No statistically significant
      difference in ecNOS staining frequency or intensity was found between different
      histologic subtypes of endometrial carcinomas. No apparent correlation was found
      between ecNOS expression and tumor stage, grade, extension to the lower uterine
      segment or cervix, nodal or distant metastases, recurrence, or final patient
      status among patients with endometrioid adenocarcinomas. Endometrioid tumors
      invading more than 1/2 of myometrial thickness (n = 18) had significantly higher
      cytoplasmic staining intensity than those tumors limited to the inner 1/2 of
      myometrium (n = 27; 2.0 vs. 1.3, p < 0.04). Furthermore, a trend toward shorter
      disease-free survival was noted with increased staining intensity and decreased
      staining frequency. CONCLUSIONS: Cytoplasmic and nuclear expression of ecNOS,
      which is primarily limited to the glandular elements of normal endometrium, is
      also found to be expressed in endometrial carcinoma. Increased ecNOS staining
      intensity and decreased frequency tends to correlate with decreased disease-free
      survival. Lastly, increased cytoplasmic ecNOS staining intensity correlates with
      increased myometrial invasion.

PMID- 9276030
TI  - Influence of neoadjuvant chemotherapy on serum tumor markers CA 15-3, MCA, CEA,
      TPS and TPA in breast cancer patients with operable disease.
AB  - Serum levels of CA 15-3, mucinous-like cancer antigen, carcinoembryonic antigen,
      tissue polypeptide antigen and tissue polypeptide-specific antigen (TPS) have
      been determined in 99 patients with T2-4 N0-1 M0 breast cancer (BC) before and
      after primary (neoadjuvant) chemotherapy and after surgery. As a whole, no
      difference in marker levels was apparent according to tumor and patient
      characteristics, with the only exception of TPS values, which showed an inverse
      relationship with the histologic grade. Serum marker levels did not substantially
      change with respect to baseline either after chemotherapy, despite the high
      response rate obtained, or after surgery. These data indicate a limited
      contribution of the primary tumor to the serum marker levels and are consistent
      for the scarce usefulness of marker evaluation in BC patients with an early stage
      of disease. Interestingly, pretreatment elevated CA 15-3 levels were correlated
      with a higher recurrence rate, further supporting the prognostic significance of
      this tumor marker.

PMID- 9276031
TI  - Association between serum gastrin levels, gastric acid secretion and age in early
      gastric cancer.
AB  - This study evaluated the effect of gastric acid secretion and serum gastrin
      response on tumor differentiation for early gastric cancer according to patients'
      age. We investigated the association between serum gastrin levels, gastric acid
      secretion and the histologic types of 335 early gastric carcinomas limited to the
      mucosal and submucosal layers in comparison with 450 gastric and 197 duodenal
      ulcers. The preoperatively examined basal acid output, maximal acid output and
      peak acid output after administration of tetragastrin and serum gastrin levels
      before and after ingestion of a test meal were determined. Patients with
      differentiated cancer and duodenal ulcer showed a significant negative
      correlation between gastric acid secretion and age, while the former group also
      had a significant positive correlation between serum gastrin levels and age. On
      the other hand, patients with undifferentiated cancer did not show any such
      correlation between gastric acid and age, but showed a significant positive
      correlation between serum gastrin, integrated gastrin response and age. Patients
      with gastric ulcer did not show any such correlations. These data suggest that
      both low acid secretion and endogenous hypergastrinemia, especially in the
      elderly, may play an important role in differentiated and undifferentiated
      gastric carcinomas.

PMID- 9276032
TI  - On managed care: the good, the bad, and the ugly.

PMID- 9276033
TI  - Uniting our forces.

PMID- 9276034
TI  - Seller beware: a modern day sham.

PMID- 9276035
TI  - Selling a medical practice: changing perspectives.

PMID- 9276036
TI  - Physicians organizations: one medical staff's experience.

PMID- 9276037
TI  - PROMINA Northwest: an integrated health system approach.

PMID- 9276038
TI  - Managed care in Macon.
AB  - The economic forces driving managed care in Macon are here to stay. Our community
      is actively involved in physician organization including our new PHO. CGHN is
      physician controlled and physician friendly. It is well capitalized, and
      physician capital outlay is minimal. It also has ownership in a potentially
      profitable HMO. We are well prepared for almost any market demand and offer
      physicians the opportunity to practice quality medicine long into the future.

PMID- 9276039
TI  - The case for an integrated independent physician association.
AB  - The State of Georgia has recognized the importance of physicians taking a strong
      leadership role in managed care with recent legislation allowing physicians to
      own and present HMO plans directly to employers. Revised antitrust guidelines
      provide opportunities for physician organizations to take on risk to compete in
      the HMO/managed care market. Physicians in an IPA have the same ability to access
      and implement management and information systems as hospitals. Imagine for a
      moment, attending a performance in the theater, when suddenly an actor rushes on
      state and shouts: "Is there a hospital administrator in the house?". No one
      doubts who the central figure in health care should be, if physicians will merely
      seize the day. We are the best spokespersons on our patient's behalf. With a
      belief in ourselves and the energy devoted to the integrated IPA format, we are
      best qualified to manage the continuing evolution of health care delivery in this
      country.

PMID- 9276040
TI  - The value of one.

PMID- 9276041
TI  - The impact of managed care on physicians' personal finances.
AB  - Ultimately, all financial decisions need to take into consideration both the
      short run implications and the four stages of your professional life. Anyone who
      attempts to advise or offer you financial products or services without
      understanding this is doing you a grave disservice. As a physician, your
      financial needs and concerns are unique, and you will be ill served by a "general
      investment practitioner" who does not work primarily or perhaps exclusively with
      physicians.

PMID- 9276042
TI  - Regionalization of trauma care.
AB  - A massive shift of patients to relatively specialized types of care has occurred.
      Until recently these patients had been treated in local centers with good results
      and at much less expense. The issue of the loss of moral authority at the local
      level is not insignificant. One cause for optimism has been the good relationship
      with neurosurgeons at several local trauma centers. This has allowed for most
      head injury patients to be treated locally, though this is not reflected in these
      data, as these patients were not transferred.

PMID- 9276043
TI  - Threats to managed care.

PMID- 9276044
TI  - New antitrust rules ease restrictions on physician networks.

PMID- 9276045
TI  - Fiction or reality? The Zagoria case and derivative professional liability.

PMID- 9276046
TI  - The arthroscopic treatment of multidirectional shoulder instability: two-year
      results of a multiple suture technique.
AB  - Nineteen consecutive shoulders in 19 patients were treated for multidirectional
      shoulder instability with an arthroscopic capsular shift. Indications for the
      procedure included complaints of pain, instability, or both that was unresponsive
      to a prescribed exercise program that stressed rotator cuff and scapular
      stabilizer strengthening. All patients had evidence of increased joint laxity on
      physical examination; 17 had a 2+ or greater sulcus test and 2 had 3+ laxity both
      anteriorly and posteriorly. Fourteen of the 19 patients were injured during
      athletic activity. All surgeries were performed in an outpatient setting. All the
      patients were evaluated at an average of 34 months postoperatively with a minimum
      follow-up of 25 months. Based on the outcome scale described by Tibone and
      Bradley, the average postoperative score was 91 out of a possible 100 with 13
      excellent, 5 good, and 1 fair result. All but 1 of the athletes returned to their
      previous level of performance but none were elite throwers. One patient had
      recurrent anterior subluxations treated with a repeat arthroscopic capsular shift
      and was rated as good. The patient rated as fair had no improvement in her pain
      after surgery. One patient complained of a painful supraclavicular suture that
      resolved spontaneously. There were no neurovascular complications or infections.
      Visualization of intra-articular pathology was enhanced with the arthroscope and
      aided in the diagnosis of multidirectional instability. The described technique
      proved safe and effective in treating multidirectional instability and enabling
      athletes to return to their previous level of function.

PMID- 9276048
TI  - Meniscus repair rehabilitation with concurrent anterior cruciate reconstruction.
AB  - Meniscal repair is preferable to meniscectomy because of the recognized benefits
      of the meniscus and the consequences of its loss. The most appropriate
      rehabilitation program after meniscus repair is unclear. Many meniscus repairs
      occur in association with anterior cruciate ligament (ACL) reconstructions. An
      accelerated program permitting early full weight bearing, unrestricted motion,
      and no limitations on pivoting sports after the resolution of the postoperative
      effusion and full motion is established encourages patients and surgeon
      acceptance of the meniscus repair. To evaluate the success of meniscus repair in
      this accelerated rehabilitation program, a consecutive series of 63 patients with
      65 meniscus tears undergoing arthroscopic meniscus repair were followed for a
      minimum of 2 years. There were seven failures (11%) at an average follow up of 38
      months. The average patient age was 26 (range, 13 to 44). Arthroscopic relooks
      were done in 26%. Successful meniscal healing occurred in 92% of repairs done
      with ACL reconstructions, but only 67% of meniscus repairs performed in ACL
      deficient knees, and 67% of meniscus repairs done in stable knees with no ACL
      injury. There was no statistical difference in the failures for acute and chronic
      meniscus tears, nor in the age of the patient undergoing the meniscal repair.
      Published rehabilitation protocols differ considerably on the three main issues
      of immobilization, weight bearing, and return to pivoting sports. These data show
      a meniscus repair success rate consistent with other published series. No
      modification of an ACL reconstruction accelerated rehabilitation program is
      needed for meniscus repairs performed in conjunction with the reconstruction.

PMID- 9276047
TI  - The arthroscopic treatment of posterior shoulder instability: two-year results of
      a multiple suture technique.
AB  - This study was undertaken to review the results of an arthroscopic posterior
      capsular shift procedure. Twenty consecutive shoulders in 19 patients were
      treated with an arthroscopic posterior capsular shift for symptomatic posterior
      shoulder instability. Patients underwent the procedure if they exhibited a
      posterior Bankart lesion or had complaints of posterior instability and evidence
      of increased posterior joint laxity on physical examination and examination under
      anesthesia. Twelve of the 20 patients were injured during athletic activity. All
      surgeries were performed in an outpatient setting. Twelve of the 20 patients had
      posterior Bankart lesions and 10 had anterior Hill-Sachs lesions. The procedure
      entails releasing the posterior labroligamentous structures from the posterior
      glenoid and freshening the glenoid neck with a bur. A suture punch is used to
      place multiple absorbable monofilament stitches in the ligament complex. The
      stitches are brought through a supraclavicular portal and tied over the clavicle
      or scapular spine. All 20 shoulders were evaluated at an average of 31 months
      postoperatively with a minimum follow-up of 24 months. Based on the outcome scale
      described by Tibone and Bradley, the average postoperative score was 83 out of a
      possible 100, with 15 excellent, 2 good, 1 fair, and 3 poor results. There were
      two recurrent dislocations and three subluxations for an overall recurrence rate
      of 25%. All the recurrences occurred in patients with posterior Bankart lesions
      and four of the five had a voluntary component to their instability. There were
      no neurovascular complications or infections. Arthroscopic evaluation facilitated
      the diagnosis of posterior instability with the visualization of intra-articular
      pathology that is difficult to identify during open procedures. Although the
      majority of patients were able to return to vigorous activities, a recurrence
      rate of 25% is disturbing and consistent with recurrence rates for open
      procedures.

PMID- 9276049
TI  - Arthroscopic microdiscectomy: comparison of preoperative and postoperative
      imaging studies.
AB  - Forty-three patients with symptomatic lumbar disc herniations underwent
      paralumbar arthroscopic disc extraction by a uniportal or biportal approach and
      postoperative imaging studies. Thirty-one patients were subjected to immediate
      postoperative computed tomography (CT) at the operative site. The other 12
      underwent magnetic resonance imaging (MRI at varying times postoperatively.
      Images obtained before and after surgery were magnified; the herniation area (H)
      and the spinal canal area (C) were measured by computerized digitization. The H/C
      ratio was calculated, and the percentage of canal clearance was obtained in each
      case. Immediate postoperative CT imaging in 16 of 18 patients with subligamentous
      and extraligamentous nonmigrated herniation showed a significant change in the
      external geometry of the annulus and canal clearance (75% to 100% canal
      clearance). Less compelling change in the postoperative CT images was
      unexpectedly seen with extraforaminal and foraminal herniations. This result may
      be attributable to limitations in our study methodology and not to inadequate
      decompression. Follow-up MRI on these patients within 8 weeks postoperatively did
      eventually show significant change in two cases that were initially not
      significant. This study confirms that the arthroscopic microdiscectomy technique
      effectively extracts herniated disc fragments and alters posterior annular
      contour, including removal of sequestered pieces.

PMID- 9276050
TI  - Autograft versus allograft anterior cruciate ligament reconstruction.
AB  - To compare the efficacy of allograft versus autograft central one third patella
      bone-tendon-bone reconstruction of anterior cruciate ligaments (ACL), subjective
      and objective criteria were compared between two groups of 30 patients with 2
      year follow-up. Over a 15-month period, 60 patients underwent ACL reconstruction
      with 30 allografts and 30 autografts. One surgeon performed all reconstructions,
      and interference fit screw fixation was used. An early rehabilitation protocol
      was instituted. At 3, 6, 12, and 24 months, allograft and autograft groups were
      compared based on side-to-side arthrometer difference, swelling, pain, range of
      motion, patellofermoral pain and crepitation, Lachman's test, pivot shift test,
      and side-to-side thigh circumference difference. Average age in the autograft
      group was 25 years (range, 15 to 43; standard deviation, 8.1), and in the
      allograft group was 27 years (range, 15 to 55; standard deviation, 10.9).
      Thirteen meniscectomies and 12 meniscal repairs were performed at the time of ACL
      autograft. Fifteen patients in the allograft group had meniscectomies, and 10 had
      meniscal repairs. There were 15 acute and 15 chronic injuries in the allograft
      group and 24 acute and 6 chronic in the autograft group. Results were analyzed
      using a chi-square test, and no statistical differences between groups were shown
      at 3, 6, 12, or 24 months for swelling, pain, side-to-side arthrometer
      difference, pivot shift test, range of motion, patellofermoral pain and
      crepitation, or Lachman's test comparisons. There was a trend for more of the
      allografts (20%) to have a glide on pivot shift at 24 months than autografts
      (7%). At 12 and 24 months, there was no difference in patellofermoral crepitus or
      thigh circumference. Complications included two patients with superficial
      infections.

PMID- 9276051
TI  - The incidence of glenohumeral joint abnormalities associated with full-thickness,
      reparable rotator cuff tears.
AB  - To evaluate the incidence of associated glenohumeral lesions in patients with a
      full-thickness rotator cuff tear, an arthroscopic examination of the glenohumeral
      joint was performed in 200 shoulders in 195 consecutive patients before
      arthroscopic rotator cuff repair. One hundred twenty-one (60.5%) had coexisting
      intraarticular abnormalities. Ninety-six (48%) had minor abnormalities, and 25
      patients (12.5%) had major coexisting intraarticular abnormalities. Major lesions
      (that required operative treatment, changed postoperative rehabilitation, or
      altered the expected end result) noted at arthroscopic examination were
      osteoarthritis in nine patients, partial biceps tendon tears in three, labrum
      tears in three, Bankart lesions in two, superior labrum anterior posterior
      lesions in five, and glenohumeral synovitis in three patients. Glenohumeral
      arthroscopy can provide valuable information in patients with a complete rotator
      cuff tear.

PMID- 9276052
TI  - Cartilage injuries: a review of 31,516 knee arthroscopies.
AB  - Although articular cartilage injuries of the knee are common, injured cartilage
      has a limited ability to heal. Recent data suggest that articular cartilage
      grafting may provide treatment for these injuries. To define the patient
      population that might benefit from cartilage grafting, 31,516 knee arthroscopies
      were reviewed. Between June 1991 and October 1995, 53,569 hyaline cartilage
      lesions were documented in 19,827 patients. The majority were articular cartilage
      lesions; grade III lesions of the patella were the most common. Grade IV lesions
      were predominantly located on the medial femoral condyle. Patients under 40 years
      of age with grade IV lesions accounted for 5% of all arthroscopies; 74% of these
      patients had a single chondral lesions (4% of the arthroscopies). No associated
      ligamentous or meniscal pathology was found in 36.6% of these patients.

PMID- 9276053
TI  - Penetration of cryotherapy in treatment after shoulder arthroscopy.
AB  - Fifteen patients undergoing shoulder arthroscopy had indwelling temperature
      probes placed in the glenohumeral and subacromial spaces. All shoulders underwent
      diagnostic arthroscopy and debridement of the subacromial space. Cryotherapy was
      delivered to the shoulder via a Cryo/Cuff (AirCast, Summit, NJ) and temperatures
      were monitored for 90 minutes. Ten shoulders received cryotherapy and 5 were used
      as controls. Before cryotherapy, temperature averaged 34 degrees C in the
      glenohumeral joint and 31 degrees C in the subacromial space. No significant
      difference was seen between the temperatures recorded in the cold therapy and
      control groups for either the glenohumeral or subacromial space. In all cases,
      the subacromial space averaged 1 degree cooler than the glenohumeral joint at the
      conclusions of arthroscopy. These slowly equalized to an average of 35 degrees
      postoperatively. The present study shows that surface-applied cryotherapy does
      not penetrate either the glenohumeral joint or the subacromial space. Attention
      must be turned elsewhere to delineate how cryotherapy works.

PMID- 9276054
TI  - The relationship between anterior cruciate ligament reconstruction tibial tunnel
      location and the anterior aspect of the posterior cruciate ligament insertion.
AB  - A retrospective study of arthroscopic anterior cruciate ligament reconstruction
      in 20 patients was conducted. These patients underwent computed tomography (CT)
      scans on the involved knee postoperatively to determine sagittal placement of the
      proximal end of the tibial tunnel (TTp) based on a distance from a specific
      anatomic reference known as the over-the-back (OTB) ridge. The distance from the
      posterior aspect of the TTp to the OTB ridge, defined as the backset, was
      measured from the CT scans. The mean backset was 6.2 mm. The anterior to
      posterior (AP) tibial plateau diameter was measured from the CT and by plain view
      radiograph. The mean AP diameter by CT scan was 55.1 mm and the mean AP diameter
      by radiograph was 55.4 mm. A Pearson correlation coefficient of r = .633
      comparing backset versus AP diameter suggests a moderately significant positive
      relationship. For the AP diameter comparing measurement method, CT versus
      radiograph, r = .985, representing a highly significant positive relationship,
      confirming AP diameter sizing accuracy by inexpensive radiography versus CT scan.
      A proposed backset model based on these data uses three fixed distances, derived
      by ratio, within a 2-mm range. This model is defined by 5-, 6-, and 7-mm backset
      intervals for < 50 mm, 50 to 60 mm, and > 60 mm AP diameters respectively, and is
      currently under prospective clinical investigation.

PMID- 9276055
TI  - A comparison of results of arthroscopic-assisted anterior cruciate ligament
      reconstruction between workers' compensation and noncompensation patients.
AB  - This investigation compared the results of arthroscopic-assisted anterior
      cruciate ligament patellar tendon autogenous reconstruction in patients who
      received Workers' Compensation (WC) benefits with results of similar surgery in
      patients who did not receive such benefits, to determine if differences existed
      based on this variable alone. Thirty-eight patients (19 WC benefits, 19 NoWC)
      were matched for age, injury chronicity, number of prior operations, and months
      of follow-up. All had the same operation and rehabilitation. A significant
      difference was found between the groups in the mean number of days of lost
      employment preoperatively (WC, 122 days; NoWC, 3 days) and postoperatively (WC,
      222 days; NoWC, 37 days). At follow-up (mean, 27 months), 17 patients in group WC
      had returned to work (6 with symptoms) and 2 were disabled. All patients in group
      NoWC had returned to work, 2 with symptoms. There was no significant difference
      between the groups for anterior-posterior displacements, functional limitations
      with daily or sports activities, patient perception of the knee condition, the
      overall rating score, or complications. The number of mean days of lost
      employment in group WC could not be accounted for from factors that normally
      effect anterior cruciate ligament reconstruction results. We hypothesize that
      other factors such as wage systems that support WC injuries long-term, inability
      of employers to modify job requirements, inability of employees to receive job
      retraining, or lack of proper immediate diagnosis and treatment of the injury,
      may have lead to the large number of lost working days in group WC.

PMID- 9276056
TI  - Meniscal transplantation and degenerative articular change: an experimental study
      in the rabbit.
AB  - Over the past several decades, scientific evidence has substantiated the vital
      role of the meniscus in the function of the knee. Using a modified Mankin method,
      this study evaluated the efficacy of immediate and delayed meniscal
      transplantation to prevent the degenerative articular changes seen after medial
      meniscectomy. Significantly fewer degenerative changes occurred in the articular
      cartilage from New Zealand white rabbits receiving a meniscal transplantation
      immediately after meniscectomy when compared with control animals killed 3 months
      after meniscectomy (P < .05). Rabbits who received a delayed transplantation 3
      months after meniscectomy and were killed at 6 months, showed significantly fewer
      degenerative changes in the articular cartilage compared with control animals
      killed 6 months (P < .05) or 3 months (P < .05) after meniscectomy. These studies
      show that both immediate and delayed meniscal allograft transplantation offer
      some initial protection to the cartilaginous surfaces of the knee following
      meniscectomy. These studies also suggest that delayed meniscal transplantation
      may reverse initial postmeniscectomy degenerative changes for the short term.

PMID- 9276057
TI  - Arthroscopic treatment of soft-tissue impingement of the ankle in athletes.
AB  - Sixty ankle arthroscopies were performed on patients with chronic soft-tissue
      impingement of the ankle after an ankle sprain between January 1989 and January
      1994. Preoperative examination findings featured tenderness localized to the
      anterolateral aspect of the ankle, no instability, and, with the exception of 2
      patients, normal radiographs. A preoperative bone scan was performed on 34
      patients and was positive in each case but was not specific. Arthroscopy was
      performed an average of 23 months after injury. Results were determined by using
      a new ankle rating score. Hypertrophic synovium, synovitis, or fibrous adhesions
      were arthroscopically visualized and resected in all cases. The average follow-up
      was 27 months (range, 6 to 64 months). Thirty-one patients underwent complete
      evaluation and 29 were evaluated over the telephone. There were 51 excellent, 7
      good, 1 fair, and 1 poor results. The diagnosis of chronic soft-tissue
      impingement of the ankle can be made from an appropriate history, thorough
      physical examination, and plain radiographs. Ankle arthroscopy with resection of
      impinging hypertrophic synovium or fibrous bands occurring after an ankle sprain
      was effective in alleviating pain in athletes.

PMID- 9276058
TI  - Arthroscopic absence of the long head of the biceps tendon.
AB  - Absence of the long head of the biceps tendon was detected during arthroscopic
      evaluation of shoulder pain in a weight-lifter. Magnetic resonance imaging and
      ultrasound showed the presence of a hypoplastic tendon with altered depth and
      width of the bicipital groove. The tendon-glenoid insertion shown by magnetic
      resonance imaging was apparently normal.

PMID- 9276059
TI  - Local arthroscopic bone grafting of a juxta-articular glenoid bone cyst.
AB  - This report describes a rare, juxta-articular bone cyst of the posterior glenoid
      that developed after a fracture of the glenoid in a 38-year-old male. The patient
      had persistent pain, popping and stiffness of his right shoulder for 3 years, and
      failed to improve after a nonoperative rehabilitation program. At arthroscopy,
      the senior author transported an autogenous bone graft from the bare area of the
      humeral head to fill the glenoid cyst arthroscopically. At second-look
      arthroscopy approximately 1 year after the index procedure, the bone graft had
      consolidated within the original cystic defect and the surface was covered with
      fibrocartilage. The graft harvest site posteriorly on the humeral head had healed
      with a small amount of scar tissue at the articular margin. Comfortable motion
      and function were restored.

PMID- 9276060
TI  - Intra-articular hemangioma of the knee with meniscal and bony attachment.
AB  - A hemangioma in the knee joint of a 37-year-old woman was diagnosed by magnetic
      resonance imaging. The case presented with pain and a tender localized swelling
      lateral to the patellar tendon. Arthroscopy verified the diagnosis but did not
      allow visualization of the full extent of the tumor. After arthroscopic subtotal
      excision of the associated hypertrophic medial plica, a miniarthrotomy was done.
      The tumor was attached to the periphery of the anterior horn of the lateral
      meniscus, to the anterior tibial plateau, and to the fat pad. It seemed to take
      its origin from the venous plexus just below the anterior lip of the central
      tibial plateau. The patient was asymptomatic 9 months after surgery. In
      hemangiomas not amenable to arthroscopic surgery, open excision through
      miniarthrotomy ensures complete removal without prolonging recovery.

PMID- 9276061
TI  - Superior detachment of a glenoid labrum variant resembling an incomplete discoid
      meniscus in a wheelchair ambulator.
AB  - Symptoms of instability and painful clunking in the shoulder were found
      associated with superior detachment of an incomplete discoid glenoid labrum and
      biceps origin in a 25-year-old woman. The patient was paraplegic below the T4
      level secondary to resection of a spinal cord astrocytoma at age of 17. Symptoms
      began after 3 years of wheelchair use and repetitive transfer injuries. On
      arthroscopic examination, only the central surface of the articular glenoid
      cartilage was visible because of labral coverage. The entire labrum was meniscoid
      without distinguishable variation. The superior labrum was in continuity with the
      root of the biceps tendon; however, the superior biceps-labral complex was
      completely stripped away from the underlying glenoid. The anterior, posterior and
      inferior labrum was firmly attached peripherally about the glenoid. An
      arthroscopic staple was used to reattach the biceps root and superior labrum to
      bone. At 6 year follow-up, the functional result was satisfactory.

PMID- 9276062
TI  - Localized pigmented villonodular synovitis: a rare cause of locking of the knee.
AB  - A 34-year-old woman presented with a history of recurrent episodes of knee
      locking and swelling. Arthroscopy revealed characteristic brown colored
      pedunculated lesions in the intercondylar notch region. These were clearly
      causing interference to joint motion. The lesions were resected arthroscopically
      with prompt resolution in symptoms. Histological examination confirmed pigmented
      villonodular synovitis.

PMID- 9276063
TI  - Destruction of a cyropreserved meniscal allograft: a case for acute rejection.
AB  - A cryopreserved nontissue-antigen-matched medial meniscus was transplanted
      arthroscopically into the knee of a 33-year-old cyclist. The patient had
      previously had an open medial menisectomy 19 years earlier and had significant
      symptoms. Ten weeks postoperatively, the patient underwent a second-look
      arthroscopy for a persistent effusion. Intraoperative cultures were obtained and
      all ultimately tested negative. The graft was found to be frayed throughout its
      length and significantly decreased in size. Its central portion had become
      detached from the peripheral repair while both the anterior and posterior bone
      blocks remained intact. Dense, inflammatory, hypertrophic synovium enveloped the
      entire joint. Histologically, the graft was found to be necrotic and acellular
      centrally, whereas the periphery was infiltrated with inflammatory leukocytes and
      giant cells. This histologic appearance is classical for an acute or subacute
      type rejection of allograft tissue.

PMID- 9276064
TI  - Impingement syndrome of the ankle caused by a medial meniscoid lesion.
AB  - Meniscoid lesion of the ankle is a well-described condition involving the
      anterolateral aspect of the ankle joint. To our knowledge, there are no reports
      of this condition involving the medial aspect of the ankle in the literature. We
      present the case of a 27-year-old man with a chronic deltoid ligament rupture who
      had developed anteromedial impingement syndrome of the ankle. The patient was
      treated with an arthroscopic debridement of the lesion and experienced a complete
      recovery.

PMID- 9276065
TI  - Consistent and accurate graft passage and interference screw guide wire placement
      during single incision anterior cruciate ligament reconstruction.
AB  - Misplacement and misalignment of trocar pins and guide wires during single
      incision anterior cruciate ligament reconstructions can lead potentially to a
      number of complications. These complications include unacceptable trocar pin exit
      locations, difficulty repositioning the trocar pin along the initial track after
      unsuccessful attempts at graft passage, as well as guide wire impingement and
      graft transection during interference screw advancement. To help overcome these
      complications, a surgical technique using an eccentric aimer and two-pin passer
      was developed to help provide precise and repeatable placement of both a trocar
      pin and guide wire.

PMID- 9276066
TI  - The adduction distraction maneuver.
AB  - The adduction distraction maneuver is presented as an adjunct to the surgeon's
      technical skills to assist with the initial introduction of the shoulder
      arthroscope. Both novice and experienced arthroscopists can experience difficulty
      establishing access to the glenohumeral joint. Often this results in articular
      cartilage or soft tissue damage. The adduction distraction maneuver when used in
      the "beach chair" seated position for shoulder arthroscopy can facilitate
      posterior portal placement and minimize iatrogenic trauma.

PMID- 9276067
TI  - The price to pay for education.

PMID- 9276068
TI  - Arthroscopic surgery--three decades.

PMID- 9276069
TI  - Chondrocyte transplantation.

PMID- 9276070
TI  - Quantitative analysis of leukocyte mitochondrial DNA deletion in affective
      disorders.
AB  - Mutations in mitochondrial DNA (mtDNA) are implicated in the pathophysiology of
      affective disorders. To determine whether the 4977-base-pair deletion in mtDNA is
      more frequent in affective disorders, we quantitated the concentration of this
      deletion in leukocyte mtDNA in 34 probands with affective disorders (20 bipolar
      and 14 unipolar) and 20 controls. We found no significant difference in the
      quantitative ratio of deletion to wild-type mtDNA between patients and controls.
      One patient with unipolar depression and 1 of 2 patients previously reported as
      having a large quantity of the deleted mtDNA did have a markedly high ratio;
      however, the deletion did not segregate with the disease in these two families.
      These results do not support a hypothesis that the 4977-base-pair deletion plays
      an important role in the pathophysiology of affective disorders.

PMID- 9276071
TI  - Stimulation of immediate early gene expression by desipramine in rat brain.
AB  - The stimulation of immediate early gene expression in brain and neuronal cell
      culture systems has been reported after various experimental paradigms such as
      chemiconvulsant-provoked seizures or specific drug applications. In particular,
      the induction of immediate early genes by adrenergic model substances has been
      demonstrated by several investigators. This report demonstrates that a single
      dose of desipramine (10 or 25 mg/kg), a classical tricyclic antidepressant drug
      acting on the adrenergic system, induced c-fos and zif268 expression in rat
      hippocampus without affecting c-jun. The observed immediate early gene response
      might reflect part of a signal transduction cascade involved in long-term
      neuroadaptive and behavioral changes after antidepressant drug treatment.

PMID- 9276072
TI  - Poststress glucose mitigates behavioral impairment in rats in the "learned
      helplessness" model of psychopathology.
AB  - Three experiments examined the effects of poststress glucose treatment in the
      learned helplessness model of psychopathology in rats. In experiment 1, rats were
      given access to water or 40% aqueous glucose immediately following exposure to
      inescapable tailshocks or simple restraint in a 2 x 2 factorial design.
      Inescapably shocked rats failed to drink the glucose solution during the
      poststress interval and failed to show any improvement 24 hours after stress
      induction in shuttle-escape performance. Consequently, all rats received
      preexposure to a sweetened glucose cocktail in an attempt to increase poststress
      ingestion following inescapable shock treatment in experiment 2. Under these
      conditions, poststress intake of the glucose cocktail eliminated behavioral
      impairment in inescapably shocked rats relative to water-treated shocked rats and
      water- and glucose-treated restrained controls. Experiment 3 demonstrated that
      glucose prophylaxis occurs in the absence of sucrose when rats are preexposed to
      a 40% glucose solution prior to stress induction.

PMID- 9276073
TI  - Effect of central and peripheral administrations of cholecystokinin-tetrapeptide
      on panic-like reactions induced by stimulation of the dorsal periaqueductal grey
      area in the rat.
AB  - Administration of cholecystokinin-tetrapeptide (CCK-4) triggers panic attacks in
      humans, but it is not known whether CCK-4 acts in the brain to produce this
      effect. Panic-like reactions (flight and tachycardia) induced in rats by
      injecting D, L-homocysteic acid (DLH) into the dorsal periaqueductal grey area
      (DPAG), were used as an animal model to investigate this issue. CCK-4 (2
      micrograms) infused into the DPAG did not change these panic-like reactions. The
      DLH-induced tachycardia was prolonged by intracerebroventricular injection of CCK
      4 (40 or 4 micrograms); however, the DLH-induced flight behavior was not changed
      by similar central injections of CCK-4 (40, 4, or 0.4 micrograms). Peripheral
      injection of t-butoxycarbonyl (BOC)-CCK-4 (40 micrograms) potentiated the flight
      behavior, but did not alter the tachycardia response. It was concluded that CCK
      tetrapeptide potentiates panic-like behaviors by acting on a peripheral target or
      on a circumventricular area of the brain. In contrast, increased brain CCK-4
      prolongs tachycardia by acting in the brain at a level distinct from the DPAG.

PMID- 9276074
TI  - Elevated levels of serum interleukin-1 beta in combat-related posttraumatic
      stress disorder.
AB  - Levels of serum interleukin-1 beta (IL-1 beta) and soluble interleukin-2 receptor
      (sIL-2R) were assessed in 19 male patients with combat-related posttraumatic
      stress disorder (PTSD) in comparison to 19 age- and sex-matched healthy
      volunteers. Serum IL-1 beta levels (but not sIL-2R) were significantly higher (p
      < .001) in the PTSD patients than in the controls. IL-1 beta levels did not
      correlate with cortisol levels, severity of PTSD, anxiety, depressive symptoms,
      or alexithymia score; however, they did correlate significantly (r = .54, p <
      .005) with the duration of PTSD symptoms. It is possible that desensitization of
      the hypothalamic-pituitary-adrenal axis in chronic PTSD patients counteracts the
      stimulatory effect of IL-1 beta on cortisol secretion.

PMID- 9276075
TI  - Lower serum zinc in major depression is a sensitive marker of treatment
      resistance and of the immune/inflammatory response in that illness.
AB  - The aims of the present study were to examine i) serum zinc (Zn) and copper (Cu)
      in treatment resistant depression (TRD); ii) the effects of subchronic
      antidepressant therapy on these trace elements; and iii) the relationships
      between serum Zn and Cu and immune/inflammatory markers. Serum Zn was
      significantly lower in TRD than in normal controls. There was a significant
      inverse correlation between baseline serum Zn and staging of depression based on
      severity of prior treatment resistance. There were no significant effects of
      antidepressive treatment on serum Zn, whereas serum Cu was significantly reduced.
      There were highly significant correlations between serum Zn and the CD4+/CD8+ T
      cell ratio (negative), and total serum protein, serum albumin, and transferrin
      (all positive). The results suggest that lower serum Zn is a marker of TRD and of
      the immune/inflammatory response in depression. It is suggested that treatment
      resistance may bear a relationship with the immune/inflammatory alterations in
      major depression.

PMID- 9276076
TI  - In vitro 1H-magnetic resonance spectroscopy of postmortem brains with
      schizophrenia.
AB  - Some evidence suggests that thalamic dysfunction could explain some of the signs
      and symptoms of schizophrenia. We measured the absolute concentrations of amino
      acid metabolites in thalamus, frontal pole, and cerebellar vermis in extracts of
      postmortem brains from 8 schizophrenics and 10 controls using high-resolution 1H
      magnetic resonance spectroscopy. The concentrations of N-acetyl aspartate,
      glutamate, and valine tended to be reduced in the thalamus of the schizophrenic
      group. Although it is difficult to ascribe significance to the "tendencies,"
      these data may tend to support other data suggesting decreased thalamic volume or
      neuronal number in schizophrenia.

PMID- 9276077
TI  - Subcortical hyperintensities on magnetic resonance imaging in patients with
      severe depression--a longitudinal evaluation.
AB  - In a longitudinal evaluation of 37 patients with severe depression who had
      undergone brain magnetic resonance imaging (MRI) 6 months-2 years (mean 14.1
      months) previously, the degree of residual dysfunction was predicted by the
      extent of subcortical white matter hyperintensities (WMHS, p < .01), longer time
      elapsed since the MRI scan (p < .05), older age (p < .05), and older age at onset
      of affective disorder (p < .05). Ten (27%) patients developed "probable" dementia
      syndromes of the vascular type, with such syndromes being predicted by WMHS (p <
      .01) and older age of onset of affective disorder (p < .05). Institutionalization
      of patients was predicted largely by the combination of chronic depression,
      progressive cognitive decline, and advanced age. The study supports the notion
      that a subgroup of patients with late-onset depressive disorders, without a
      family history of depression, and with risk factors to cerebrovascular disease,
      have extensive WMHS on MRI, and that such structural brain changes predispose to
      chronic depression and progressive cognitive decline.

PMID- 9276078
TI  - Synergism of lorazepam and electroconvulsive therapy in the treatment of
      catatonia.
AB  - Electroconvulsive therapy (ECT) and lorazepam are effective treatments for
      catatonia. ECT combined with benzodiazepines has been associated with reduced
      efficacy and efficiency and therefore is not recommended in the routine practice
      of ECT. We report 5 prospectively identified cases of catatonia treated either
      sequentially or concurrently with lorazepam and ECT. In each case, the
      combination of lorazepam with ECT was superior to monotherapy. This apparent
      synergism, its possible mechanisms, and its implications for treating catatonia
      are discussed.

PMID- 9276079
TI  - Mismatch negativity during attend and ignore conditions in Alzheimer's disease.
AB  - Mismatch negativities (MMNs) of the event-related potential to deviant tones and
      environmental sounds were recorded during active and ignore oddball sequences in
      young and elderly controls and patients with probable Alzheimer's disease (PAD).
      MMNs were smaller in the PAD waveforms compared to those of the controls,
      suggesting a degraded sensory memory trace in these subjects; however, under
      ignore conditions, environmental sounds elicited robust MMNs in the PAD group
      along with N2b and novelty P3 components in similar fashion to controls. As N2b
      and P3 are usually elicited by attended stimuli, these data suggest that in the
      PAD subjects, the highly deviant events involuntarily captured attention, perhaps
      reflecting the activation of an attentional switching mechanism. Because this
      passive switching is thought to reflect activation of a mechanism located in the
      frontal lobes, the data suggest that this putative frontal lobe mechanism is
      relatively intact in the early stages of the disease.

PMID- 9276080
TI  - Psychiatric symptom-provoking studies: an ethical appraisal.

PMID- 9276081
TI  - Obsessive-compulsive disorder following bilateral globus pallidus infarction.

PMID- 9276082
TI  - Platelet endogenous adenosine 5'-diphosphate ribosylation in drug-free and
      lithium-treated subjects with bipolar disorder.

PMID- 9276083
TI  - Plasma tryptophan levels and prolactin response to fenfluramine in healthy
      volunteers.

PMID- 9276084
TI  - Obesity, and bone strength and "mass": a tutorial based on insights from a new
      paradigm.

PMID- 9276085
TI  - Insulin-like growth factors and osteoporosis.

PMID- 9276086
TI  - Circulating and skeletal insulin-like growth factor-I (IGF-I) concentrations in
      two inbred strains of mice with different bone mineral densities.
AB  - Recent work has demonstrated differences in femoral bone mineral density between
      two common inbred strains of mice, C3H/HeJ (C3H) and C57BL/6J (B6), across a wide
      age range. To investigate one possible mechanism that could affect acquisition
      and maintenance of bone mass in mice, we studied circulatory and skeletal insulin
      like growth factor-I (IGF-I) and femoral bone mineral density (F-BMD) by pQCT in
      C3H and B6 progenitor strains, as well as serum IGF-I obtained from matings
      between these two strains and mice bred from subsequent F1 intercrosses (F2).
      Serum IGF-I measured by radioimmunoassay was more than 35% higher in virgin
      progenitor C3H than virgin B6 at 1, 4, 8, and 10 months of age, and in 8-month
      old C3H compared with B6 retired breeders (p < 0.001). In the progenitors, there
      was also a strong correlation between serum IGF-I and serum alkaline phosphatase
      (r = 0.51, p = 0.001). In the 4 month F1 females IGF-I levels and F-BMD were
      intermediate between C3H and B6 progenitors. In contrast, groups of F2 mice with
      the highest or lowest BMD also had the highest or lowest serum IGF-I (p =
      0.0001). IGF-I accounted for > 35% of the variance in F-BMD among the F2 mice.
      Conditioned media from newborn C3H calvarial cultures had higher concentrations
      of IGF-I than media from B6 cultures, and cell layer extracts from C3H calvariae
      exhibited greater alkaline phosphatase activity than cultures from B6 calvarial
      cells (p < 0.0001). The skeletal content of IGF-I in C3H tibiae, femorae, and
      calvariae (6-14 weeks of age) was also significantly higher than IGF-I content in
      the same bones of the B6 mice (p < 0.05). These data suggest that a possible
      mechanism for the difference in acquisition and maintenance of bone mass between
      these two inbred strains is related to systemic and skeletal IGF-I synthesis.

PMID- 9276087
TI  - Monoclonal antibodies reactive with human osteogenic cell surface antigens.
AB  - Monoclonal antibodies (McAbs) against the surface of osteoblastic cells have been
      used to characterize the osteogenic lineage. In view of the paucity of probes
      against the surface of normal human osteogenic cells, we sought to generate McAbs
      which could be used for both in vivo and in vitro studies. We raised a series of
      McAbs against early osteoblastic cell surface antigens by immunizing mice with
      human mesenchymal stem cells (MSCs) that had been directed into the osteogenic
      lineage in vitro. After screening against the surface of osteogenic cells at
      various stages of differentiation in vitro, as well as evaluating in situ
      reactivity with human fetal limbs, we isolated three hybridoma cell lines
      referred to as SB-10, SB-20, and SB-21. Immunocytochemical analyses during
      osteogenic differentiation demonstrate that SB-10 reacts with MSCs and
      osteoprogenitors, but no longer reacts with cells once alkaline phosphatase
      (APase) is expressed. Flow cytometry documents that SB-10 is expressed on the
      surface of all purified, culture-expanded human MSCs, thus providing further
      evidence that these cells are a homogeneous population. By contrast, SB-20 and SB
      21 do not react with the progenitor cells in situ, but bind to a subset of the
      APase-positive osteoblasts. None of these antibodies stain terminally
      differentiated osteocytes in sections of developing bone. Furthermore, these
      McAbs were not observed to react in samples from chick, rat, rabbit, canine, or
      bovine bone, although selected extraskeletal human tissues were immunostained. In
      all cell and tissue specimens examined, SB-20 immunostaining is identical to that
      observed with SB-21. We have used these McAbs to refine our understanding of the
      discrete cellular transitions that constitute the osteogenic cell lineage. We
      suggest a refined model for understanding osteoblast differentiation that is
      based on the proposition that the sequential acquisition and loss of specific
      cell surface molecules can be used to define positions of individual cells within
      the osteogenic cell lineage.

PMID- 9276088
TI  - Nonenzymatic glycation of type I collagen modifies interaction with UMR 201-10B
      preosteoblastic cells.
AB  - Advanced glycation endproduct (AGE), whose formation is accelerated on long lived
      extracellular matrix proteins in diabetes, is implicated in diabetic
      complications in various tissues. Type I collagen is the predominant matrix
      protein of bone and plays an important role in bone cell-matrix interactions. We
      have previously reported the accelerated accumulation of AGE collagen in bone
      tissue in diabetes mellitus (DM), in which reduced bone mineral density was
      observed. In addition, when cultures of mature primary rat osteoblasts were
      plated onto an in vitro AGE-modified collagen substrate, they showed altered cell
      functions, in terms of alkaline phosphatase (ALP) activity, osteocalcin
      secretion, and nodule formation (J Bone Miner Res 11:931-937; 1996). To determine
      whether AGE collagen might also affect differentiation of preosteoblasts, we
      compared the effects of plating the preosteoblastic UMR 201-10B cell line onto
      AGE-modified collagen with plating onto unmodified collagen. The latter had been
      shown previously to promote differentiation of UMR 201 cells. We have also
      explored whether these effects might be partly mediated by the transforming
      growth factor beta (TGF-beta) receptor. Growth of UMR 201-10B cells on a type I
      collagen substrate significantly inhibited cell growth and retinoic acid (RA)
      induced upregulation of ALP activity, compared to cells on plastic. These
      inhibitory effects were reduced by prior glycation of collagen, in a dose
      dependent manner with respect to AGE content. Unmodified collagen stimulated
      production of osteopontin mRNA, which was reduced by AGE modification to levels
      attained in cells on plastic. Growth on control collagen inhibited TGF-beta type
      II receptor binding in 10B cells, while this inhibition was reduced by AGE
      modification. These data suggest that glycation of collagen interferes with
      specific interaction(s) between UMR 201-10B cells and collagen. Based on our
      previous results in UMR 201 cells, these results would be compatible with the
      notion that glycated collagen has reduced ability to promote differentiation of
      preosteoblasts to mature osteoblasts. These data further suggest that collagen
      mediated events in these cells may be at least in part mediated by regulation of
      the TGF-beta receptor expression.

PMID- 9276089
TI  - Leukemia inhibitory factor is mitogenic to osteoblasts.
AB  - Leukemia inhibitory factor (LIF) regulates cell growth and is produced by a
      variety of tissues, including bone. Previously we have shown that recombinant
      human LIF induced an increase in osteoclast number, bone formation, and DNA
      synthesis. In the present study, we have defined the cells in intact bone at
      which the proliferative effects of LIF occur, using simultaneous enzyme
      histochemistry and autoradiographic techniques. The area of alkaline phosphatase
      positive staining was increased twofold (p = 0.0008) and the number of
      [3H]thymidine-positive cells was increased twofold (p = 0.0024) in LIF-treated
      bones. The radiolabeled cells either colocalized with alkaline phosphatase or
      were in the osteoprogenitor region. They were not found in the acid phosphatase
      positive staining osteoclasts. These results indicate that cells which have a
      mitogenic response to LIF are bone-forming rather than bone-resorbing cells.

PMID- 9276090
TI  - Rapid and long-term effects of PTH(1-34) on growth plate chondrocytes are
      mediated through two different pathways in a cell-maturation-dependent manner.
AB  - The aims of this study were to clarify the role of cell maturation stage on
      chondrocyte response to parathyroid hormone (PTH) by examining the effect of
      PTH(1-34) on alkaline-phosphatase-specific activity (ALPase) of chondrocyte
      cultures at two distinct stages of maturation, and to determine the signaling
      pathways used by the cells to mediate this effect. Confluent, fourth passage rat
      costochondral resting zone (RC) and growth zone (GC) chondrocytes were used.
      ALPase was measured in the cell layer, as well as in matrix vesicles (MV) and
      plasma membranes (PM), after the addition of 10(-7) 10(-11) mol/L bovine PTH(1
      34), the active peptide, or bovine PTH(3-34), the inactive peptide, to the
      cultures. PTH(1-34) increased ALPase in the GC cultures at two separate times:
      between 5 and 180 min, with maximal stimulation at 10 min, and 36 to 48 h. In
      contrast, PTH(3-34) had no effect. At 10 min and 48 h, PTH(1-34) produced a dose
      dependent increase in ALPase of both MV and PM isolated from GC cultures.
      Addition of forskolin and IBMX to increase cAMP increased ALPase in GC cultures
      to a level similar to that seen after addition of PTH(1-34). In contrast, the
      addition of PTH(1-34) to RC cells only increased ALPase between 5 and 60 min,
      with peak activity at 10 min. As with GC, PTH increased ALPase in both MV and PM.
      Moreover, the addition of PTH(3-34) or forskolin and IBMX had no effect on ALPase
      in RC. PTH(1-34) had no effect on GC protein kinase C (PKC) activity; however,
      the addition of PTH(1-34) to RC caused a dose-dependent increase in PKC activity.
      H8, an inhibitor of PKA, had no effect on PTH-stimulated ALPase in RC cells, but
      inhibited the PTH-dependent response in GC cells. In contrast, chelerythrine, an
      inhibitor of PKC activity, inhibited PTH-stimulated ALPase in RC cells, but had
      no effect on PTH-stimulated ALPase in GC cells. This study shows that the effect
      of PTH(1-34) on RC and GC cells is maturation dependent in terms of time course
      and mechanism. Whereas both cell types exhibit a rapid response to PTH, only GC
      cells show a long-term response. In GC, the effects of PTH are associated with
      changes in cAMP and may also involve at least one other pathway, whereas, in RC,
      the PTH effects appear to be associated with changes in PKC.

PMID- 9276091
TI  - Morphological and structural characteristics of the proximal femur in human and
      rat.
AB  - Because the ovariectomized rat model of postmenopausal osteoporosis is the most
      commonly used small animal model to investigate consequences of bone loss on bone
      structure and strength, or to assess benefits of the various therapeutic
      strategies to improve bone mass and strength, the attempt was made to compare
      histoanatomical and structural characteristics of the femoral neck between human
      and rat models. In addition to different biomechanics, there is a significant
      difference in gross- and microanatomy of the proximal femur between humans and
      rats. Percent of the cortical bone component is much higher in rats (72.5%)
      relative to humans (12.5%). Also, cortical bone at the femoral neck in rats is
      evenly distributed, whereas in humans there is a considerable difference in the
      amount of the cortical bone between the superior half of the femoral neck with
      cortical thickness being only 0.3 mm, and the inferior half of the neck having 6
      mm-thick cortex. Humans have far more cancellous bone at the femoral neck (22.7%
      average) relative to rats (6.8%). In addition, cancellous bone at the femoral
      neck in humans is unevenly distributed between the bone center and its periphery.
      Human samples exhibited striking differences in the cancellous bone structure
      between weight-bearing and tensile trabecular groups exhibiting clear trabecular
      orientation consisting of plates and rods, and trabeculae around the neutral bone
      axis with little mechanical activity exhibiting rod-like trabeculae only.
      Although humans and rats have a periosteum covering the femoral neck, and each
      lacks the muscular attachment at intracapsular portions of the femoral neck,
      rats, in contrast to humans, have the ability to quickly adapt cortical thickness
      and increase inertia to meet mechanical needs via modeling-dependent periosteal
      apposition.

PMID- 9276092
TI  - Effects of calcitonin gene-related peptide on bone turnover in ovariectomized
      rats.
AB  - Calcitonin gene-related peptide (CGRP) is a neuropeptide abundantly concentrated
      in sensory nerve endings innervating bone metaphysis and periosteum, which
      indicates that it plays a local role in bone metabolism. CGRP-alpha and -beta
      share structural and functional homology with calcitonin (CT) and have been shown
      to inhibit bone resorption in vitro and to induce hypocalcemia in vivo. We
      recently reported that CGRP stimulates the production of the growth factor
      insulin-like growth factor-I and inhibits that of the cytokine tumor necrosis
      factor-alpha by osteoblasts, suggesting that CGRP may control bone cell activity.
      To investigate this possibility, we used ovariectomized (ovx) rats as a high bone
      turnover model and compared the effects of CGRP to those of CT. ovx young female
      rats were injected daily starting the day after surgery with either phosphate
      buffered saline, CGRP-alpha (1.15 mg/kg per day), or CT (3 micrograms/kg per day)
      for 28 days. Ovariectomy induced an increase in bone turnover associated with a
      60% loss in trabecular bone volume of the proximal tibia. CGRP inhibited bone
      resorption but not bone formation, and was nevertheless less efficient than CT in
      preventing bone loss, since CGRP-treated rats had a loss of 46% of cancellous
      bone, whereas CT-treated rats had a loss of 21%. This suggests that CGRP is
      either less potent than CT at inhibiting bone resorption or else very rapidly
      degraded. These data indicate that CGRP can control bone cells through a
      mechanism that is in part different from that of CT, and further suggest that
      CGRP may play a local role in bone metabolism.

PMID- 9276094
TI  - Three-dimensional imaging of trabecular bone using the computer numerically
      controlled milling technique.
AB  - Although various techniques exist for high-resolution, three-dimensional imaging
      of trabecular bone, a common limitation is that resolution depends on specimen
      size. Most techniques also have limited availability due to their expense and
      complexity. We therefore developed a simple, accurate technique that has a
      resolution that is independent of specimen size. Thin layers are serially removed
      from an embedded bone specimen using a computer numerically controlled (CNC)
      milling machine, and each exposed cross section is imaged using a low
      magnification digital camera. Precise positioning of the specimen under the
      camera is achieved using the programmable feature of the CNC milling machine.
      Large specimens are imaged without loss of resolution by moving the specimen
      under the camera such that an array of field-of-views spans the full cross
      section. The images from each field-of-view are easily assembled and registered
      in the postprocessing. High-contrast sections are achieved by staining the bone
      black with silver nitrate and embedding it in whitened methylmethacrylate. Due to
      the high contrast nature and high resolution of the images, thresholding at a
      single value yielded excellent predictions of morphological parameters such as
      bone volume fraction (mean +/- SD percent error = 0.70 +/- 4.28%). The main
      limitations of this fully automated "CNC milling technique" are that the specimen
      is destroyed and the process is relatively slow. However, because of its
      accuracy, independence of image resolution from specimen size, and ease of
      implementation, this new technique is an excellent method for ex situ imaging of
      trabecular architecture, particularly when high resolution is required.

PMID- 9276093
TI  - Prevention of corticosteroid-induced bone loss with nitric oxide donor
      nitroglycerin in male rats.
AB  - Nitric oxide (NO) has been reported to inhibit osteoclastic bone resorption. We
      examined the bone sparing effect of NO on prevention of corticosteroid-induced
      bone loss in older male rats. Recently, we demonstrated that NO donor
      nitroglycerin (NG) can alleviate ovariectomy-induced bone loss, and the
      protective effects of estrogens on bone are mediated through NO [Bone 18(4):301
      304; 1996]. Therefore, we chose to study a different model (i.e., steroid-induced
      osteoporosis in males) to evaluate whether NG can inhibit the bone loss
      associated with corticosteroid therapy. Twenty-five 32-week-old male Wistar rats
      were randomly assigned to five groups (n = 5/group). They received either
      vehicle, methylprednisolone (7 mg/kg per week), NO synthase inhibitor L-NAME (25
      mg/kg per day), NO donor nitroglycerin (NG, 0.2 mg twice daily), a combination of
      prednisolone+NG, or prednisolone plus L-NAME, respectively. Prior to treatment
      and at the end of the 6 week treatment period, bone mineral density (BMD) of the
      lumbar spine was measured by dual energy X-ray absorptiometry scanning.
      Administration of prednisolone significantly decreased BMD (-9.50%, p < 0.05).
      The group receiving NG with prednisolone (-2.34%) and the group treated with NG
      alone (-0.36%) were not statistically different from the control group (-0.11%).
      Similar to the changes in BMD, femur weights were also significantly lower in
      prednisolone-treated rats (1.09 +/- 0.01 g vs. 1.17 +/- 0.03 in controls; p <
      0.05). However, the rats receiving prednisolone together with NG were able to
      maintain their femur weights (1.13 +/- 0.02). There was a reduction of 9.5% of
      BMD (p < 0.05) and 7.8% of femoral weight (p < 0.05) in rats treated with L-NAME.
      A 50%-70% reduction of the percentage trabecular bone volume in the proximal
      tibia and distal femur and a 50% reduction of the midshaft cortical area was seen
      after corticosteroid therapy, and these too were prevented by administration of
      NG. Here, we demonstrate, for the first time, that supplementation with a NO
      donor compound can counteract prednisolone-induced bone loss.

PMID- 9276095
TI  - Effect of bovine bone constituents on broadband ultrasound attenuation
      measurements.
AB  - Broadband ultrasound attenuation (BUA) has been found to correlate positively
      with bone mineral density (BMD) measured by dual-energy X-ray absorptiometry.
      However, because there is a significant amount of unexplained variation in this
      correlation, it has been suggested that BUA might also provide information about
      bone structure. The purpose of this study was to determine the contribution of
      bone mineral and organic matrix to BUA and BMD measurements. The influence of
      sample length on both BUA and BMD was also investigated by normalizing these
      measurements to length. BUA (Walker Souix, 575+) and BMD (Lunar DPX) values were
      obtained on bicortical cores removed from 12 bovine femoral necks. BMD and BUA
      measurements were repeated on the samples after: (1) mechanical removal of the
      cortices; (2) defatting using a 2:1 chloroform:methanol solution; and (3)
      decalcifying using formic acid. The data demonstrate that the cortical component
      of the bone contributes significantly to BMD. We found that 41.7% of the
      normalized BMD reflect cortical bone. Defatting the samples did not affect BUA.
      Decalcifying the trabecular bone while maintaining an intact collagenous
      structure significantly reduces BUA by 89% and BMD by 96% compared to the whole
      core samples. Normalizing BMD and BUA to sample length, in cases where large
      variation is present, does influence the correlation between the variables. We
      conclude that BUA is influenced mainly by the presence of bone mineral, whereas
      the presence of the organic matrix contributes very little to BUA.

PMID- 9276096
TI  - Hearing aids: past, present, future: moving toward normal conversations in noise.

PMID- 9276097
TI  - Self-rated hearing disability in candidates for cochlear implants.
AB  - A previous scheme for quantification of hearing disability based on self-rating
      required extrapolation towards the upper end of the range due to lack of data
      from severely and profoundly impaired subjects. Suitable data have become
      available more recently from the UK programme evaluating cochlear implantation,
      thereby providing self-ratings by 465 people with 1-2-3-kHz average hearing
      threshold levels of 95 dB or greater. The ratings obtained fit the previous
      extrapolation extremely well. The scheme, therefore, can be applied with
      confidence to people throughout the range of hearing impairment.

PMID- 9276098
TI  - Normal and hearing-impaired word recognition scores for monosyllabic words in
      quiet and noise.
AB  - The effects of noise on word recognition scores were assessed with normal-hearing
      and hearing-impaired subjects. Fifty-one normal-hearing subjects were tested at
      50 dB HL using signal-to-noise ratios (S/Ns) of 5, 10, and 15 dB. Thirty subjects
      with mild-to-moderate sensorineural hearing losses were tested in quiet and in
      noise at S/Ns of 10 dB and 15 dB. Monosyllabic words in a Multitalker Noise were
      selected for testing. Mean scores for the normal-hearing subjects were 45% at the
      5 dB S/N, 74% at the 10 dB S/N, and 87% at the 15 dB S/N. For the hearing
      impaired subjects, scores were 85% in quiet, 60% at the 15 dB S/N, and 40% at the
      10 dB S/N. These results suggest that background noise which is mildly disruptive
      for normal hearing subjects can be highly disruptive to hearing-impaired
      subjects. Moreover, these findings indicate that subjects with mild-to-moderate
      sensorineural hearing loss require a more favourable S/N than normal listeners to
      achieve comparable word recognition scores. Test-retest differences for word
      recognition scores revealed variability that agreed closely with predictions
      based on the binomial distribution for both groups of subjects. Speech-in-noise
      abilities must be measured directly because regression equations revealed that
      speech-in-noise scores cannot be predicted accurately from either puretone
      thresholds or speech-in-quiet scores. Word recognition functions are presented
      from several hearing-impaired subjects and demonstrate the value of testing in
      noise.

PMID- 9276099
TI  - Effect of hearing impairment on educational outcomes and employment up to the age
      of 25 years in northern Finland.
AB  - The association between hearing impairment in adolescence and school performance
      and the outcome of education was studied among 25-year-old subjects followed
      since pregnancy in the Northern Finland birth cohort. The series, 395 subjects
      with abnormal hearing and 977 randomly selected controls, was based on a
      questionnaire on hearing and school achievement sent to 11780 members of the
      cohort alive at the age of 14 years, and on audiometric screening test requested
      from health centers. Hearing loss was defined as 'clinically significant' if the
      pure tone average (PTA; mean of the thresholds at 0.5, 1 and 2 kHz) exceeded 25
      dB in the better ear; a threshold of > or = 30 dB at 4 kHz and a PTA of < or = 25
      dB as '4 kHz loss'; and as 'slightly abnormal' if any of the thresholds exceeded
      20 dB at any frequency and the case did not belong to the above two categories.
      The more severe the hearing impairment, the poorer was the child's performance at
      elementary school. Those with normal hearing and those with a slightly abnormal
      or 4 kHz loss were equally often accepted for intermediate education (88%), while
      those with a clinically significant loss had the lowest acceptance figures (64%).
      When adjusting for neurological and social confounders, excluding mental
      disability, the risk of not qualifying from intermediate or higher education at
      all was twice as high among those with a clinically significant loss as among the
      controls (OR 2.1, 95% CI 1.13-3.8), and was still elevated after adjustment had
      been made for all the relevant perinatal, neurological and social factors (OR
      1.9, 95% CI 1.02-3.6). 14% of those with a clinically significant hearing loss,
      9% of the subjects with a 4 kHz loss and 7% of those with normal hearing were
      unemployed at the age of 25 years. Hearing impairment appears to have effects on
      both the outcome of education and employment status.

PMID- 9276100
TI  - Acquired deafness: a multi-dimensional experience.
AB  - The aim of this study was to investigate the subjective experience of acquired
      deafness using quantitative (questionnaire) and qualitative (interview) methods.
      This paper presents findings from the questionnaire data. Eighty-seven people (of
      whom 38 had acquired a profound loss) participated in the study. The
      questionnaire contained items designed to examine both audiological and non
      audiological aspects of deafened people's experiences. It also sought to measure
      the extent to which those aspects affect their quality of life. The questionnaire
      included three variables (i.e. reported frequency and impact of depression, and
      overall effect of deafness on one's life) as broad indicators of adjustment.
      Seventy-three respondents (including all but one of the profound group) completed
      the questionnaire. Factor analysis of the questionnaire data identified six major
      themes (with variance > 10%) underlying the personal experience of acquired
      deafness. Three themes--communicative deprivation, restriction, and
      malinteraction by hearing people--dealt with observable aspects of respondents'
      experience. Multiple regression found that these factor themes associated with
      biomedical variables. The remaining three themes dealt with less tangible aspects
      of the deafness experience. These themes--feelings of distress in interaction,
      feelings of abandonment and benefit from positive experiences--did not associate
      with biomedical variables. Finally, multiple regression indicates that
      respondents' factor scores predict the impact of deafness at least as strongly as
      their audiological and social characteristics.

PMID- 9276102
TI  - The decision to make a movement: neurophysiological insights.
AB  - It is unclear how the brain enables a subject to discriminate between two or more
      sensory stimuli and to respond appropriately to them. This process must include
      the ability to detect and identify the stimuli, and to select and initiate an
      appropriate motor response. With the advent of improved computer technology, this
      behavior can now be studied in the laboratory, not only by monitoring the input
      to (stimulus) and output from the brain (response), but also by measuring the
      associated electrical activity of the brain in order to gain an understanding of
      how this task is accomplished. In this paper we discuss our work in this area and
      its relevance to understanding the neural organization of the decision to make a
      movement in response to a sensory stimulus.

PMID- 9276103
TI  - Familial cerebral aneurysms.
AB  - Familial cerebral aneurysms are currently the subject of burgeoning interest. We
      review the pertinent, recent reports on this topic in the light of our study of
      17 families with familial cerebral aneurysms. The prevalence of familial cerebral
      aneurysms ranges from 5-28%. The sex distribution displays a female bias. Mothers
      are more often affected than fathers and daughters more than sons. There is no
      site predilection for familial cerebral aneurysms but they tend to occur at the
      same (or mirror) site within families. The age at rupture of familial cerebral
      aneurysms is younger, especially in females, than for sporadic aneurysms. They
      tend to rupture within the same decade in families, and within five years of each
      other in identical twins. The size of ruptured familial cerebral aneurysms
      appears to be smaller, especially in women, than sporadic aneurysms. The pattern
      of inheritance is unknown. A poor outcome of rupture is more frequent in familial
      cerebral aneurysms cases than in sporadic ones. Angiographic screening of family
      members at risk, especially first degree relatives, appears justified.

PMID- 9276101
TI  - Developmental changes in tympanometry: a case study.
AB  - The use of 226 Hz tympanometry in neonates and infants has been controversial due
      to the large number of false negative responses for middle ear pathology. A
      review of the literature highlights several anatomical differences between this
      population and that of the adult, which is not recognized during interpretation
      of their tympanograms. The aim of the study was to document tympanometric changes
      in a single child using 226 Hz, 1000 Hz and sweep frequency probe tones until she
      was 6.5 months old. Both 226 Hz and 1000 Hz tympanograms show a maturational
      change in middle ear resonance from a mass to a stiffness-dominated system, which
      was corroborated by sweep frequency probe tones. It is suggested that high
      frequency probe tones were able to increase test sensitivity to the mechanics of
      the middle ear when it was mass-dominated, as in this infant. Due to the large
      intersubject variability reported in the literature, it is recommended that both
      high and conventional probe tone tympanograms are performed in infants under 6
      months of age to increase diagnostic accuracy. Middle ear resonance can also be
      determined for each individual enabling more appropriate selection of probe tones
      for Y, B and G tympanometry.

PMID- 9276104
TI  - Cellular adhesion molecules in neurology.
AB  - The study of cellular adhesion molecules offers crucial understanding of cellular
      interactions. Their name implies an underestimation of their function, as
      intercellular glue. In fact, they play vital roles in tissue development and
      intra- and intercellular signaling. In neurology, cellular adhesion molecules are
      already providing welcome new insight into neurodevelopmental anomalies,
      autoimmune demyelination, and invasive tumours. Cellular adhesion molecule
      manipulation has led to several therapeutic options which are the subject of
      ongoing clinical investigation.

PMID- 9276105
TI  - Intracranial dural arteriovenous fistulae with pial venous drainage: combined
      endovascular-neurosurgical therapy.
AB  - BACKGROUND: Intracranial dural arteriovenous fistula with pial venous drainage
      may present with hemorrhage or focal neurologic deficit and may be difficult to
      treat. We wish to summarize the therapeutic approaches to these potentially
      dangerous lesions and to demonstrate how endovascular and neurosurgical therapies
      may have complimentary roles in their management. METHODS: The clinical and
      radiological records of all patients who presented to our institution with
      intracranial dural arteriovenous fistula over the last 5 years were reviewed. In
      those cases demonstrating pial venous drainage, details of presentation, imaging
      features, endovascular and surgical therapy and outcome were analyzed. RESULTS:
      We identified 13 patients with these lesions, 7 of whom presented with
      intracranial hemorrhage. Six patients were treated with embolization alone.
      Angiographic cure was achieved in 4. There was one complication in this group, a
      subarachnoid hemorrhage following glue injection. Four patients were treated with
      embolization followed by surgical occlusion of the pial venous drainage.
      Angiographic cure was achieved in all 4. There was one complication in this
      group, a facial nerve palsy following glue injection. Three patients were treated
      by surgery alone, with no complications and complete cure in all. CONCLUSION:
      Endovascular therapy of intracranial dural arteriovenous fistula may be curative
      but is often complex and carries definite risks. Neurosurgical ligation of pial
      draining veins, with pre-operative embolization when safe, may be a relatively
      more controlled method to achieve complete cure.

PMID- 9276106
TI  - Pediatric pseudotumor cerebri: descriptive epidemiology.
AB  - OBJECTIVE: To determine the epidemiological profile for pediatric pseudotumor
      cerebri. METHODS: A retrospective case series was identified from a
      geographically limited region of 205,765 children aged 2-15 years at the only
      tertiary care pediatric hospital with all pediatric neurologists and
      ophthalmologists. Health records identified 35 children with ICD9 code 348.2
      (benign intracranial hypertension) presenting between April 1, 1979 and March 31,
      1994. After chart review, 29 cases were identified which satisfied modified
      Dandy's diagnostic criteria for pseudotumor cerebri. RESULTS: The 29 cases ranged
      in age from 3-15 years. The annual incidence of symptomatic disease was 0.9 per
      100,000 children (95% CI 0.6, 1.4). Cases were 2.7 times more likely to be female
      (21/29, X2 p = .01) and twice as likely to be adolescent (age 12-15 years), (X2 p
      = .04). Based upon these distinctions, the following estimates of age and sex
      specific disease incidence were derived (based upon 100,000 child years of
      exposure): male age 2-11 years: 0.4; male age 12-15 years: 0.8; female age 2-11
      years: 1.1; female age 12-16 years: 2.2. CONCLUSIONS: These data appear to be
      unique for its the estimation of age and sex specific incidence rates for
      pediatric pseudotumor cerebri.

PMID- 9276107
TI  - Seizure control after stimulation of the vagus nerve: clinical outcome measures.
AB  - BACKGROUND: Currently, decreases in seizure frequency are the accepted efficacy
      outcome measure of therapeutic interventions in the management of patients with
      epilepsy. In a longitudinal randomized controlled trial of 10 subjects with
      intractable complex partial seizures who received left vagal nerve stimulation
      (VNS) to control seizures, it was found that the total number of consecutive
      seizure-free days is a significant efficacy outcome measure. Unlike measures in
      which percentage decreases in seizure frequency are calculated, measures of
      consecutive seizure days indicate improvement in the amount of time for which
      patients may function at a higher level in activities of daily living. METHODS:
      Fourteen day blocks of consecutive seizure-free days and 14 day blocks of
      consecutive days in which subjects had seizures were tabulated. RESULTS: A
      Pearson correlation coefficient showed that prior to VNS subjects had few, if
      any, seizure free blocks of time and after VNS they had more blocks of time
      seizure free r = -1.00 and r = -0.99. The blocks of seizure-free days increased
      tenfold (mean 0.85 to mean 8.00) from 1991-1995 while mean seizure frequency in
      those blocks in which subjects had seizures only decreased from (mean 20.14 to
      mean 17.59) for the same time period. Correlations between total number of
      seizures after 24 months of VNS and after 50 months of VNS were r = 0.85 showing
      a consistency in the effect of VNS. CONCLUSIONS: Monitoring the number of
      consecutive seizure-free days is a significant clinical outcome measure of VNS.

PMID- 9276108
TI  - Chronic stimulation of the left vagus nerve: cognitive motor effects.
AB  - BACKGROUND: Early studies of cognitive motor control have shown deficits in
      complex reaction time tests of epileptic subjects. The purpose of this efficacy
      study was to determine whether chronic (28 months) stimulation of the left vagus
      nerve (VNS) to control seizures increased these deficits in 6 epileptic subjects
      with intractable complex partial seizures. METHODS: Subjects were assessed for
      simple reaction time, Test A, and subsequent Tests B and C which involved more
      complex cognitive strategies. Tests were done pre-operatively (SI) and at
      intervals, 6-8 weeks (S2-S3), and at 6 month intervals (S4-S6) over a 28 month
      period. Data were collected and collated on an Apple II E computer (Apple,
      Cupertino CA. U.S.A.) and on electronic switch pad. Data were analyzed using a
      repeated measures analysis of covariance technique with 2 within subject factors,
      day, and time of day. RESULTS: 2/11 cognitive measures showed a statistically
      significant difference. Error rate associated with Test A (simple reaction time)
      significantly decreased for the factor of day (repeated visits) p = .01. For Test
      C, error rates decreased in the afternoon (p = .03). This test involved the
      subjects ability to respond quickly to one signal while simultaneously ignoring a
      second signal. Data analysis of the covariate showed that the effects of VNS are
      weak in comparison to baseline differences and the frequency of nerve stimulation
      negatively predicts the number of wrong errors. High frequency stimulation
      results showed fewer errors than low frequency stimulation T = -2.31, p = .03.
      CONCLUSION: Chronic stimulation of the left vagus nerve to control seizure
      activity does not impair cognitive motor control.

PMID- 9276109
TI  - Chronic stimulation of the left vagus nerve in epilepsy: balance effects.
AB  - BACKGROUND: Stimulation of the left vagus nerve (VNS) has been shown to control
      seizures in double blinded crossover studies in man. Animal studies have reported
      vagal afferent induced depression of nociceptive and motor reflexes which may be
      caused by an effect on the descending reticular system controlling spinal cord
      function. Anticonvulsant drug therapy may cause postural instability. The effects
      of VNS are assessed not only from the perspective of seizure control but also
      from the view of potential harm to other bodily systems. Long term (2 1/4 years)
      effects of VNS were compared to postural stability analyses. METHODS: 8 subjects,
      2 were females, mean age 34.5 +/- 8.23 SD years, with intractable complex partial
      seizures, taking 3 anticonvulsant drugs were assessed for postural stability in
      quiet standing and while moving forwards, backwards and sideways with eyes open
      (EO) and eyes closed (EC). Data were collected and collated using an AMTI
      Biomechanics immovable forceplate, Newton M.A. U.S.A. The study design was
      longitudinal with pre-operative baseline data collected prior to neurostimulation
      and at intervals post operatively. RESULTS: 4/8 balance measures showed
      significant changes from pre-operative values and after 2 1/4 years of
      stimulation. Area of sway (EO) in quiet standing p = .022 and total sway (EC) in
      the moving state p = .019 and total sway (EC) in quiet standing showed an
      increase in sway p = .003. Area of sway (EC) p = .004 tended to decrease.
      Regression analysis for frequency of stimulation showed an increase in sway with
      higher frequencies T = 1.99, P = .05. CONCLUSION: Chronic VNS does not augment
      postural instability.

PMID- 9276110
TI  - Does teleradiology improve inter-hospital management of head-injury?
AB  - OBJECTIVE: In many countries, neurosurgical care is concentrated in regional
      centres, which often necessitates the inter-hospital transfer of patients with
      head injury for optimal treatment. The aim of this study was to evaluate the role
      of teleradiology in the management of head-injured patients when-referred from a
      district general hospital to a tertiary neurosurgical centre. METHODS:
      Prospective data were collected over a fifteen month period from March '95 to May
      '96. Head-injured patients referred without the facility of teleradiology (Group
      1), were compared to similar patients referred with teleradiologic images (Group
      2), with particular regard to therapeutic intervention before transfer and
      adverse events during transfer. RESULTS: There were 28 patients in Group 1 and 35
      in Group 2, of which 31 were transferred. Both groups were comparable with
      respect to age, admission Glasgow Coma Scale score, and intracranial pathology.
      For patients transferred with teleradiology consultation (Group 2), therapeutic
      interventions were more (32.1% vs. 10.7%, p = 0.06), adverse events during
      transfer were significantly lower (6.4% vs. 32.1%, p = 0.01), and transfer time
      was reduced (72 vs. 80 minutes, p = 0.38). Four patients in Group 2 were treated
      by a mobile neurosurgical team at the referring hospital because of rapid
      clinical deterioration. CONCLUSION: Our findings indicate that teleradiology has
      an important role in improving inter-hospital management of head-injured
      patients.

PMID- 9276111
TI  - Weight gain in epileptic patients during treatment with valproic acid: a
      retrospective study.
AB  - BACKGROUND: Weight gain has been recognized as a common adverse effect of
      valproic acid (VPA) that leads to discontinuation in some patients but its
      incidence and correlates have been rarely studied. METHODS: We have analyzed the
      records retrospectively and interviewed 70 adult patients attending an epilepsy
      clinic on VPA mono- or polytherapy followed over a median of 27 months (range 3
      189), as well as 20 patients on carbamazepine (CBZ) monotherapy. Patients were
      divided into non-weight gainers (< 5% baseline body weight), mild-moderate weight
      gainers (5-10% body weight) and marked weight gainers (> 10% body weight). The
      following variables were statistically analyzed to determine their relationship
      to weight gain: gender, age, body mass index, drug dose, personal or family
      history of obesity and monotherapy versus polytherapy. RESULTS: Seventy-one
      percent of the VPA group were weight gainers versus 43% in the CBZ group. A
      weight gain of more than 4 kg in 70% of the VPA group was observed. The weight
      gain was often sustained and frequently socially significant to the patients.
      Patients below or within normal range body mass index prior to the start of VPA
      experienced the most severe percentage weight gain. From the structured patient
      interviews, patients with no personal history of weight problems experienced the
      greatest initial weight increase. CONCLUSION: Strategies should be devised to
      help patients avoid weight gain when starting on VPA, especially if they are not
      already overweight.

PMID- 9276112
TI  - Cross sensitivity of skin rashes with antiepileptic drugs.
AB  - BACKGROUND: Skin rashes are a well known complication of antiepileptic drug (AED)
      treatment. It has also been recognized that some patients will develop rashes
      from multiple AEDs (cross sensitivity). There are very few studies that have
      attempted to determine the frequency of cross sensitivity among AEDs. METHODS:
      Charts of all patients attending an epilepsy outpatient clinic were reviewed to
      determine AED exposure and the occurrence of a rash from AEDs. RESULTS: 633
      patients had 1,875 exposures to 14 AEDs. Rashes occurred from carbamazepine (N =
      27), phenytoin (N = 21), phenobarbital (N = 5) and lamotrigine (N = 1). A rash
      from 2 or more AEDs occurred in 14 patients and involved predominantly
      carbamazepine and phenytoin. Among the patients exposed to both phenytoin and
      carbamazepine 10/17 (58%) of patients with a rash from phenytoin also had a rash
      from carbamazepine; conversely 10/25 (40%) patients with a carbamazepine rash
      also had a rash from phenytoin. 4/5 patients with a phenobarbital rash were
      sensitive to carbamazepine and/or phenytoin. Amongst the other most commonly used
      AEDs no rashes occurred from valproic acid or clobazam. CONCLUSIONS: The cross
      sensitivity rate for rashes involving carbamazepine and phenytoin is 40-58%. If a
      rash develops from either of these AEDs, valproate or clobazam are safe
      alternatives.

PMID- 9276113
TI  - Acromegaly with normal basal growth hormone levels.
AB  - BACKGROUND: The most common cause of acromegaly is excess of growth hormone (GH)
      secretion. METHODS: We report a 42-year-old male patient, who had become
      acromegalic over the past 5 years. There were no visual changes or change in
      sexual function, no gynaecomastia or galactorrhoea. Both CT and MRI scans showed
      a large mass measuring 2.5 x 2.5 x 3.5 cm, originating from the sella turcica and
      extending into and totally filling up the sphenoid sinus with diffusely invasive
      features. RESULTS: Basal serum GH level was within normal range, but insulin-like
      growth factor 1 (IGF-1) was elevated with slightly increased prolactin (PRL) and
      impaired GH secretory regulation as well. A pituitary adenoma was partially
      removed through transsphenoidal microsurgery. Pathology confirmed a mammo
      somatotrophic adenoma but immunocytochemistry study of the tumour showed only
      positivity for PRL but not GH. CONCLUSIONS: When acromegaly occurs without GH
      level elevation, one should pay attention that: 1) IGF-1 might be the cause of
      the clinical feature of acromegaly; 2) The tumour might undergo morphological
      transformation; and 3) Hyperinsulinemia or GH receptor antibody formation could
      also be the cause of the acromegalic appearance.

PMID- 9276115
TI  - Clusterophobia.

PMID- 9276114
TI  - Jean-Martin Charcot's contributions to the interface between neurology and
      psychiatry.
AB  - Although much has been written about Jean-Martin Charcot (1825-1893) as a
      neurologist and his commitment to the hysterics of the Salpetriere, his influence
      on modern psychiatric thought has been misunderstood. His contributions range
      from the diagnosis and understanding of certain aspects of hysteria, which
      influenced psychoanalysis, to insights into the psychopathology of trauma that
      foreshadow modern concepts of post-traumatic stress disorder and somatoform
      disorders. This article reviews these aspects in the context of his contributions
      as a founder of modern neurology, neuropathology and proponent of the anatomo
      clinical approach.

PMID- 9276116
TI  - Current views on the prevention of postoperative infectious endophthalmitis.

PMID- 9276118
TI  - Bacterial endophthalmitis following extracapsular cataract extraction:
      recommendations for early detection.
AB  - OBJECTIVE: To determine the time between the onset of symptoms of endophthalmitis
      after cataract extraction and presentation to an ophthalmologist and to determine
      the spectrum of organisms responsible for postoperative endophthalmitis. DESIGN:
      Case series. SETTING: Tertiary care vitreoretinal service in Toronto. PATIENTS:
      Thirty-three patients with early (presentation within 2 weeks of surgery)
      endophthalmitis following extracapsular cataract extraction and intraocular lens
      implantation performed between January 1989 and December 1992. OUTCOME MEASURES:
      Time to presentation to an ophthalmologist, duration of symptoms, culture
      results. RESULTS: Twenty-two patients (66.7%) were documented to experience
      identifiable symptoms of endophthalmitis before presentation to their
      ophthalmologist; the mean time of onset of symptoms was 3.6 (standard deviation
      [SD] 1.7) days after surgery. Of the 22 patients 16 (72.7%) became symptomatic by
      the fourth postoperative day, and 21 (95.4%) experienced symptoms by the fifth
      postoperative day. The mean delay between onset of symptoms and presentation was
      1.9 (SD 1.6) days. Bacteria were identified in 27 cases (81.8%), confirmed by
      culture in 23 cases (69.7%). The organisms were gram-positive in 25 (92.6%) of
      the 27 cases, and coagulase-negative Staphylococcus predominated. CONCLUSIONS: In
      our series a considerable delay existed between the development of symptoms of
      endophthalmitis following extracapsular cataract extraction and clinical
      diagnosis. This delay could be minimized by scheduling routine postoperative
      visits at 1 and 4 days following cataract surgery.

PMID- 9276117
TI  - Postoperative endophthalmitis: incidence, predisposing surgery, clinical course
      and outcome.
AB  - OBJECTIVE: To describe the predisposing surgery, clinical course and final visual
      outcome for patients with culture-proven and culture-negative postoperative
      endophthalmitis. DESIGN: Case series. SETTING: University-affiliated teaching
      hospital in Toronto. PATIENTS: A total of 164 patients with clinically suspected
      postoperative endophthalmitis admitted between January 1989 and March 1996.
      OUTCOME MEASURES: Type of surgery, clinical presentation, culture results,
      infecting organism, treatment and final visual outcome. RESULTS: An infectious
      agent was identified in 99 cases (60%). The organism most commonly isolated was
      coagulase-negative Staphylococcus (59 cases [60%]). In the culture-proven group
      cataract extraction was the most common predisposing surgical procedure,
      accounting for 85 cases (extracapsular cataract extraction [ECCE] in 60 cases and
      phacoemulsification in 25). The incidence rates of culture-proven endophthalmitis
      over the study period at our institution were 0.22% for ECCE and 0.30% for
      phacoemulsification. Of the 99 patients with culture-proven endophthalmitis 94
      received intravitreal injections of antibiotics and 52 underwent vitrectomy. Of
      the 83 patients in this group for whom the final outcome was known, 29 (35%) had
      a visual acuity of 20/50 or better, and 15 (18%) had a vision of no light
      perception, with four eyes undergoing enucleation. Infection with organisms of
      low virulence (coagulase-negative Staphylococcus or Propionibacterium acnes) was
      associated with higher rates of 20/50 or better visual acuity compared with more
      virulent organisms (Staphylococcus aureus, streptococcal species and gram
      negative bacilli) (46% vs. 10%) (p < 0.05). The culture-negative group had a
      significantly lower frequency of hypopyon on presentation (55% vs. 85%) and final
      outcome of no light perception (2% vs. 18%) (p < 0.01) than the culture-proven
      group. CONCLUSIONS: Endophthalmitis was most common after cataract surgery. The
      rates of endophthalmitis after ECCE and phacoemulsification were similar.
      Postoperative endophthalmitis caused by organisms other than coagulase-negative
      Staphylococcus or P. acnes carries a poor visual outcome.

PMID- 9276119
TI  - Practices associated with cataract surgery in Canada: results of a national
      survey.
AB  - OBJECTIVE: To examine Canadian ophthalmologists' reported practices related to
      cataract surgery. DESIGN: Mailed questionnaire survey. SETTING: Canada.
      PARTICIPANTS: Random sample of 698 ophthalmologists from the mailing list of the
      Canadian Ophthalmological Society. Of the 528 eligible ophthalmologists 353
      completed the questionnaire (response rate 67%). A total of 276 respondents were
      classified as cataract surgeons (performed at least one cataract operation in the
      preceding year [1992]) and were included in the study. OUTCOME MEASURES: Reported
      use of preoperative ophthalmic tests, surgical technique, cataract anesthesia
      (including type of block and who administers it) and postoperative care. RESULTS:
      Most of the preoperative tests examined either were so routine as to be done in
      almost all cases or were rarely done at all. A total of 52% of the respondents
      were identified as predominantly extracapsular cataract extraction surgeons
      (ECCE), 46% as predominantly phacoemulsification surgeons and 2% as predominantly
      intracapsular cataract extraction surgeons. Overall, 57% of the respondents
      reported high use of retrobulbar anesthesia, 18% reported high use of peribulbar
      anesthesia, and 0.7% reported high use of general anesthesia. The mean number of
      postoperative visits in the first 4 months after surgery was 4.25. The mean rate
      of Nd:YAG laser capsulotomy in the first year after cataract surgery was 17.9%;
      91% of the respondents reported a rate less than 40%. CONCLUSIONS: There seems to
      be limited use of nonessential preoperative ocular testing by Canadian cataract
      surgeons. Although ECCE remains the most common type of surgery performed, there
      appears to be a substantial number of surgeons trying phacoemulsification, and
      this will likely become the predominant technique in the near future. The self
      reported practices of Canadian surgeons with relation to preoperative testing and
      postoperative follow-up appear to be consistent with the Clinical Practice
      Guideline for cataract surgery set by the US Agency for Health Care Policy and
      Research. However, variations in the number of postoperative visits and Nd:YAG
      capsulotomy rates merit further investigation.

PMID- 9276120
TI  - Flicker perimetry in diabetic children without retinopathy.
AB  - OBJECTIVE: To determine the flicker fusion frequency in children and adolescents
      with insulin-dependent diabetes mellitus (IDDM) who did not have fluorescein
      angiographic signs of retinopathy. DESIGN: Cross-sectional study. SETTING:
      Antidiabetic Centre, departments of Ophthalmology and Pediatrics, University of
      Chieti, Chieti, Italy. PATIENTS: Forty-five patients aged 9 to 18 years with IDDM
      without fluorescein angiographic signs of retinopathy. Forty-five healthy
      subjects matched for sex and age constituted the control group. The patients were
      classified into two subgroups according to their metabolic control: good
      (percentage hemoglobin Alc 9% or less) or poor (percentage hemoglobin Alc greater
      than 9%). OUTCOME MEASURES: Retinal flicker fusion frequency, evaluated with an
      automated flicker perimeter in the central 30 degrees of the visual field.
      RESULTS: The subjects with poor metabolic control had a significantly lower mean
      flicker fusion frequency than the control subjects (27.43 Hz [standard deviation
      (SD) 5.16 Hz] vs. 38.72 Hz [SD 4.27 Hz]) and the patients with good metabolic
      control (33.94 Hz [SD 5.54 Hz]) (p < 0.001). There was a significant relation
      between flicker fusion frequency and the percentage of hemoglobin Alc (r = 
      0.533, p < 0.001). CONCLUSIONS: Our results show that children with poorly
      controlled IDDM without fluorescein angiographic signs of retinopathy have an
      impairment of retinal flicker sensitivity in the central 30 degrees of the
      central visual field and that this impairment is related to the degree of
      metabolic control. Flicker perimetry is a simple, noninvasive tool that may be
      useful to evaluate the eye function of diabetic children.

PMID- 9276121
TI  - Histopathology of the retinal pigment epithelium of a female carrier of
      choroideremia.

PMID- 9276122
TI  - Orbital hydatid cyst.

PMID- 9276123
TI  - Ring melanoma of the anterior uvea presenting as unilateral neovascular glaucoma.

PMID- 9276125
TI  - Levels of evidence and interventional ophthalmology.

PMID- 9276124
TI  - Retinal vascular occlusions complicating acute toxoplasmic retinochoroiditis.

PMID- 9276126
TI  - Pharmacological heterogeneity of neurotensin receptors: an in vitro study.
AB  - Neurotensin (NT), a linear tridecapeptide, has been shown to exert a variety of
      biological effects in the periphery and in the central nervous system. The aim of
      the present study was to characterize the NT receptors mediating the contractions
      of two isolated organs, the rat stomach strip and the guinea pig ileum. More than
      20 compounds, peptides, nonpeptides, or pseudopeptides, were tested for their
      agonistic and antagonistic effects against NT and a series of potent analogs or
      fragments. Receptors were characterized using the two classical criteria
      suggested by Schild, the order of potency of agonists and the affinity of
      antagonists. The results shown in this study indicate that the contractions of
      the guinea pig ileum in response to NT are mediated by acetylcholine and
      prostaglandins because they are blocked by atropine and indomethacin. The
      contractions induced by NT in the rat stomach are not influenced by atropine,
      indomethacin, methysergide, and diphenhydramine and may result from the direct
      activation of smooth muscle receptors. Differences in the order of potency of
      agonists were also found between the two preparations: in the rat stomach strip,
      the order of potency was AcNT(8-13) > Arg-NT(8-13) > Lys-NT(8-13) > NT = NT(8-13)
      and in the guinea pig ileum was Arg-NT(8-13) > AcNT(8-13) > NT = NT(8-13) > Lys
      NT(8-13). The nonpeptide antagonist SR 48692 was shown to possess higher apparent
      affinity for the rat stomach functional sites (pA2 8.0) than for those of the
      guinea pig ileum (pA2 6.45). The results presented in this paper suggest that two
      different pharmacological entities may subserve the myotropic effect of NT and
      some analogs and fragments in the gastrointestinal tract of the guinea pig and
      the rat.

PMID- 9276127
TI  - Neurokinin receptors (NK1, NK2) in the mouse: a pharmacological study.
AB  - Experiments were performed on strips of mouse stomach and urinary bladder to
      characterize the receptors involved in the contractile responses of these tissues
      to neurokinins (substance P (SP), neurokinin A (NKA), neurokinin B (NKB), and
      neuropeptide gamma (NP gamma). The neurokinin receptors were characterized by
      using assays with selective agonists as well as peptide and nonpeptide
      antagonists and by applying the two Schild criteria for receptor classification,
      namely, the order of potency of agonists and the apparent affinity of competitive
      antagonists. The mouse stomach contains primarily NK1 and NK2 functional sites
      and possibly some NK3 receptors, whereas the urinary bladder possesses only the
      NK2 receptor. The rank order of potency of agonists in the stomach is
      Ac[Arg6,Sar9,Met(O2)11]SP-(6-11) > NKA > SP > [beta-Ala8]NKA-(4-10) > NKB >
      [MePhe7]NKB. Among the selective agonists, Ac[Arg6,Sar9,Met(O2)11]SP-(6-11) is
      more active than SP and [Sar9,Met(O2)11]SP on the NK1 receptor, whereas the order
      of potency on the NK2 receptor is NKA > NP gamma > or = [beta-Ala8]NKA-(4-10) >
      [Nle10]NKA-(4-10). The order of potency of agonists in the bladder is NP gamma >
      NKA > [beta-Ala8]NKA-(4-10). The myotropic responses mediated by NK1 selective
      agonists are blocked by SR 140333 (pA2 8.57) and those mediated by the NK2
      selective agonists are inhibited by SR 48968 (pA2 9.05). RP 67580 (pA2 8.41) is
      more active than CP 99994 (pA2 6.06) on the mouse NK1 receptor. The NK1 receptor
      of the mouse shows, therefore, a pharmacological profile similar to that of the
      NK1 receptor of the rat. Similarly, MEN 10627 (pA2 9.20) is more active than R
      396 (pA2 6.21), suggesting that the mouse NK2 receptor is similar to that of the
      rabbit. The mouse NK2 receptor of the urinary bladder shows similarity with that
      of the stomach, but is less sensitive to [beta-Ala8]NKA-(4-10).

PMID- 9276128
TI  - Antagonists for kinin B1 and B2 receptors in the mouse.
AB  - Contractile responses to B1 and B2 receptor agonists have been demonstrated in
      the mouse stomach; the mouse urinary bladder responds only to B2 receptor
      agonists. These tissues were used in this study to investigate the antagonistic
      effect of four B2 receptor antagonists, namely, DArg[Hyp3,DPhe7,Leu8]BK (BK,
      bradykinin), HOE-140, WIN 64338, and FR-173657 (B2 receptor antagonists), as well
      as three B1 kinin receptor antagonists; [Leu8]desArg9BK, Lys[Leu8]desArg9BK, and
      AcLys[D beta Nal7,Ile8]desArg9BK, were investigated. Results shown indicate that
      DArg[Hyp3,DPhe7,Leu8]BK is a partial agonist, while HOE-140 and FR-173657 are
      pure antagonists, devoid of direct myotropic effects, and quite selective for the
      B2 receptor. WIN 64338 was essentially inactive on both B1 and B2 receptors. The
      myotropic effect of DArg[Hyp3,DPhe7,Leu8]BK is blocked by HOE-140. Similarly,
      Lys[Leu8]desArg9BK and [Leu8]desArg9BK are B1 receptor partial agonists whose
      activities are blocked by AcLys[D beta Nal7,Ile8]desArg9BK (code name R 715), a
      fairly pure B1 receptor antagonist. Both HOE-140 and FR-173657 are long-acting,
      slowly reversible compounds that exert a noncompetitive type of antagonism, while
      R 715 is rapidly reversible and, thus, possibly competitive. Data presented in
      this paper provide a pharmacological characterization of B1 and B2 receptor
      antagonists in the mouse and underline the positive features of FR-173657 as a
      potent and selective B2 receptor antagonist, as well as the potency and purity of
      R 715 as a B1 receptor antagonist in the mouse.

PMID- 9276129
TI  - Bradykinin-induced translocation of cytoplasmic phospholipase A2 in MDCK cells.
AB  - The nonapeptide bradykinin (BK) plays an important role in the production of
      eicosanoids within the collecting duct of the nephron. We have shown previously
      that BK can initiate a complex signaling cascade that causes the release of
      arachidonic acid (AA) from MDCK-D1 cells, a canine cell line of distal tubule and
      collecting duct origin. This release is dependent upon early activation of
      specific upstream enzymes, including phosphatidylcholine-specific phospholipase C
      (PC-PLC) and phospholipase D (PLD). Ultimately, the release of this precursor of
      eicosanoids is effected by recruitment of the cytoplasmic 85-kDa form of
      phospholipase A2 (cPLA2). This enzyme is thought to translocate from the cytosol
      to cellular membranes following stimulation by agonists that cause elevations of
      intracellular calcium ([Ca2+]i). The present study was undertaken to examine the
      dependence of AA release upon Ca2+ influx in BK-stimulated MDCK cells. For this
      purpose, cells were incubated with 1 microM BK for 1 min and lysed in Ca(2+)-free
      Tris buffer. The high-speed 100000 x g pellet was extracted with 10 mM octyl
      glucoside and the cPLA2 protein level was determined. Previous results from our
      laboratory indicated that BK induced a 1.81-fold increase in cPLA2 activity
      associated with cellular membranes, while in the present study, Western blotting
      with a specific cPLA2 antibody demonstrated a similar elevation in protein
      detected with these same membranes. A selective inhibitor of receptor-mediated
      Ca2+ entry, SK&F 96365, was used to resolve the role of extracellular Ca2+ in
      BK's ability to evoke AA release. Pretreatment of cells with SK&F 96365 resulted
      in an inhibition of greater than 60% of the BK response. Taken together, these
      results strongly suggest that BK-mediated AA release in MDCK-D1 cells is at least
      partly contingent upon translocation of cPLA2 to membranes initiated by an influx
      of extracellular Ca2+.

PMID- 9276130
TI  - Characterization of a specific binding site for angiotensin II in chicken liver.
AB  - We have characterized a specific binding site for angiotensin II (AngII) in
      chicken liver membranes. Pseudo-equilibrium studies at 22 degrees C for 30 min
      have shown that this binding site recognizes AngII with a high affinity (pKD of
      8.13 +/- 0.21). The binding sites are saturable and relatively abundant (maximal
      binding capacity varies from 0.318 to 0.88 pmol/mg of protein). Nonequilibrium
      kinetic analyses at 22 degrees C revealed a calculated kinetic pKD of 8.77 +/-
      0.20. The binding site is pharmacologically distinct from the classic AngII
      receptors AT1 and AT2. Competitive binding studies with chicken liver membranes
      demonstrated the following rank order of effectiveness: AngII (human; Asp-Arg-Val
      Tyr-Ile-His-Pro-Phe) > AngI(Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu) > AngIII(Arg
      Val-Tyr-Ile-His-Pro-Phe) > AngIV (Val-Tyr-Ile-His-Pro-Phe) > Ang(1-7) (Asp-Arg
      Val-Tyr-Ile-His-Pro) > PD123319 (1-[4(dimethylamino)3-methylphenyl] methyl-5
      (diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo [4,5-c]pyridine-6-carboxylic acid)
      > DuP753 (2-n-butyl-4-chloro-5 hydroxymethyl-1-[(2'-1H-tetrazol-5-yl)biphenyl-4
      yl)methyl] imidazole. This atypical AngII binding site (chicken AT) was sensitive
      to increasing concentrations of DTT and Mn2+. The structure-activity relationship
      on position 1 of AngII showed that the primary N-terminal amine was essential for
      binding affinity ([Asp1]AngII > [Suc1]AngII > or = [Sar1]AngII), but
      modifications of the side chain in position 1 had less influence on the affinity
      ([Gly1]AngII > [Cys1]AngII approximately [aminoisobutyryl1]AngII approximately
      [Ser1]AngII > > > [Sar1]AngII). The presence of substantial quantities of this
      binding site in chicken liver membranes suggests the possibility that the chicken
      AT may play an important, yet unrecognized, role in the renin-angiotensin system.

PMID- 9276131
TI  - Effects of dexamethasone on the basal and cytokine-stimulated release of
      endothelin-1 from guinea-pig cultured tracheal epithelial cells.
AB  - Endothelins (ETs) are potent bronchoconstrictor agents postulated to contribute
      to the pathophysiology of asthma and other respiratory disorders. An increase in
      both the expression and release of immunoreactive (ir) ETs was reported in
      bronchial epithelial cells and the bronchoalveolar lavage fluid of asthmatic
      patients. We investigated whether dexamethasone (DEX), a potent anti-inflammatory
      and anti-asthmatic drug, regulates the basal and stimulated release of ETs from
      guinea-pig cultured tracheal epithelial cells. These airway epithelial cells
      spontaneously release ET-1 over 24 h. When incubated in the presence of 10(-7)
      and 10(-6) M DEX for 24 h, basal production of ET-1 decreased by 32 and 29%.
      Lipopolysaccharide (LPS; 1, 5, 10 micrograms/mL), tumor necrosis factor-alpha
      (TNF alpha; 5, 10 ng/mL), and interleukin-1 beta (IL-1 beta; 1, 5 ng/mL)
      significantly increased the basal release of ET-1 after 24 h. When these cells
      were pretreated with DEX (10(-7) M) for a 24-h period, then incubated in the
      presence of LPS (10 micrograms/mL), TNF alpha (10 ng/mL), or IL-1 beta (1 ng/mL)
      for another 24 h, the stimulated release of ET-1 was inhibited by 48, 31, and
      38%, respectively. At 10(-6) M, DEX decreased the stimulated release by 45, 37,
      and 46%, respectively. The present results show that DEX can regulate the basal
      release and inhibit the pro-inflammatory cytokine-stimulated production of ET-1
      from guinea-pig cultured tracheal epithelial cells. They suggest that the
      beneficial effect of glucocorticoids in asthma may be related to the inhibition
      of ET synthesis.

PMID- 9276132
TI  - Role of tachykinin NK1 and NK2 receptors on colonic motility in anesthetized
      rats: effect of agonists.
AB  - Tachykinins fulfill general criteria to be considered as neurotransmitters
      neuroeffectors in the mammalian enteric nervous system; however, little
      information is available about their role in the regulation of intestinal
      motility in vivo. The present study investigates the effect of selective
      tachykinin receptor agonists on colonic motility in urethane-anesthetized rats.
      Colonic motility was recorded by means of a balloon-catheter device (filled with
      0.5 mL of water) inserted for 7 cm through the rectum. In atropine- and
      guanethidine-pretreated rats, the NK1 receptor agonist [Sar9]substance P sulfone
      (0.3-300 nmol/kg i.v.) dose dependently induced phasic contractions followed by
      an enhancement in the amplitude and frequency of spontaneous contractions. In
      three of six cases, a transient inhibition (3-5 min) of spontaneous motility was
      also evident after the phasic contraction. All these effects were reduced by the
      NK1 receptor antagonist SR 140333 (1 mumol/kg i.v.). In atropine- and
      guanethidine-pretreated rats and in the presence of SR 140333 (1 mumol/kg i.v.),
      the NK2 receptor agonist [beta-Ala8]neurokinin A-(4-10) (0.3-300 nmol/kg i.v.)
      induced a dose-dependent tonic contraction, but the amplitude and frequency of
      spontaneous contractions were not changed. NK2 receptor antagonists such as MEN
      11420 (0.01-1 mumol/kg i.v.), MEN 10627 (1 mumol/kg i.v.), or SR 48968 (1
      mumol/kg i.v.) reduced the effect of [beta-Ala8]neurokinin A-(4-10). The present
      results indicate that NK2 receptor stimulation evokes a pure excitatory effect on
      colonic motility whereas NK1 receptor stimulation induces both excitatory and
      inhibitory effects.

PMID- 9276133
TI  - Tachykinin-induced contractions of the guinea pig ileum longitudinal smooth
      muscle: tonic and phasic muscular activities.
AB  - In vitro tachykinin-induced contractions of guinea pig ileum longitudinal smooth
      muscle were investigated under isometric conditions by using selective agonists
      ([Sar9,Met(O2)11]substance P, [Nle10]neurokinin A-(4-10), senktide) and
      antagonists (SR 140333, SR 48968, SR 142801), respectively, for the tachykinin
      NK1, NK2, and NK3 receptors. [Sar9,Met(O2)11]Substance P (10 nM) induced a tonic
      contraction with superimposed phasic contractions. Both tonic and phasic muscular
      activities were completely abolished by SR 140333 (10 nM) and were not modified
      by SR 142801 (10 nM). SR 48968 (10 nM) and atropine (0.001 mM) did not modify the
      tonic muscular activity but inhibited the phasic muscular activity.
      [Nle10]Neurokinin A-(4-10) (10 nM) only caused a phasic contractile response that
      was inhibited by SR 48968. Atropine, SR 140333, and SR 142801 were without
      effect. Senktide (1 nM) induced combined tonic and phasic contractile responses.
      SR 142801 blocked the phasic and tonic muscular activities, whereas SR 48968 and
      SR 140333 were inactive. After addition of atropine, only tonic contractile
      response was abolished. These results showed fundamental differences in isometric
      tonic and phasic contractile responses of guinea pig ileum longitudinal smooth
      muscle to tachykinins.

PMID- 9276134
TI  - Pharmacological profiles of the human and rabbit B1 receptors.
AB  - Twenty-two peptides related to kinins were used (i) to examine some chemical
      features required for the human and rabbit B1 receptor activation or blockade and
      (ii) to establish the existence of a correlation between the pharmacological
      spectrum of the B1 receptor obtained on the rabbit aorta (rbA) and the human
      umbilical vein (hUV). The apparent affinities of these peptides were measured in
      vitro using classical bioassays and are expressed in terms of pD2 (for agonists)
      or pA2 values (for antagonists). Selectivity for the B1 receptor was demonstrated
      by testing the peptides against the effect of bradykinin (BK) on the hUV and the
      rabbit jugular vein (rbJV), two preparations containing B2 receptor-mediating
      vasoconstriction. The results show that (i) lysyl-peptide agonists and
      antagonists demonstrate higher affinities than nonlysyl compounds on human and
      rabbit B1 receptors, (ii) peptides containing hydrophobic D-residues (e.g., Tic,
      beta Nal, Hyp(trans-propyl), Igl) in position 7 are suitable for B1 receptor
      antagonism, and (iii) the additive substitution of an Oic residue in position 8
      leads to nonselective kinin receptor antagonists. Moreover, a high (r = 0.92) and
      positive (regression slope = 0.99 +/- 0.09) correlation between the affinities
      measured for the kinin analogues in two B1 receptor bioassay systems has been
      revealed. Based on the similarity of pharmacological profiles observed in the
      rabbit and human B1 receptors, we suggest that the B1 receptor domain in which
      peptide agonists and antagonists interact may be similar in these two species.

PMID- 9276135
TI  - Endothelins potentiate formalin-induced nociception and paw edema in mice.
AB  - The present study investigates the influence of endothelin (ET) related peptides
      (0.3-30 pmol/paw) on both phases of nociception and on edema induced by
      intraplantar injection of formalin (0.5% in 20 microL) in the mouse hind paw. The
      first phase of nociception (0-5 min after injection) was significantly
      potentiated by simultaneous injection of either ET-1 (10 or 30 pmol/paw) or ET-3
      (10 pmol/paw), but not of the selective ET3 receptor agonist sarafotoxin S6c
      (SRTX-c; up to 30 pmol/paw). All three peptides potentiated the second phase (10
      30 min after injection) of formalin-induced nociception (at 3-30, 1-30, and 10-30
      pmol/paw for ET-1, ET-3, and SRTX-c, respectively), whereas only ET-1 (10 or 30
      pmol/paw) effectively enhanced edema caused by formalin (30 min after injection).
      Histamine also potentiated all three responses triggered by formalin, but was 30-
      to 100-fold less potent than ET-1. Treatment with the mixed ETA/ETB receptor
      antagonist bosentan (10 mg/kg i.p., 1 h beforehand) did not influence nociceptive
      and edematogenic responses to formalin or their potentiation by histamine (3
      nmol/paw), but did inhibit the potentiations induced by ET-1 (10 pmol/paw). Thus,
      ET-1 potentiates formalin-induced nociception and edema in the mouse. These
      actions are possibly mediated via ETB and ETA receptors, respectively, but their
      true identity and the mechanisms involved still remain to be fully elucidated.

PMID- 9276136
TI  - Antagonistic effects of FR 173657 on human, pig, rabbit, and guinea pig kinin
      receptors: an in vitro study.
AB  - The pharmacodynamic features of the new nonpeptide kinin B2 receptor antagonist
      FR 173657 were evaluated on pig, rabbit, guinea pig, and human native kinin B2
      receptors. FR 173657 exerted high antagonistic activity in all preparations
      examined. In particular, it acts as a competitive antagonist in the rabbit
      jugular vein (pA2 8.9) and in the human umbilical vein (pA2 8.2) but as a
      noncompetitive antagonist in the pig coronary artery (pKB 9.2) and in the guinea
      pig ileum (pKB 9.2) stimulated with the selective B2 receptor agonist bradykinin
      (BK). In contrast, FR 173657 failed to antagonize the biological effects of the
      selective B1 receptor agonist LysdesArg9BK in the pig renal vein, rabbit aorta,
      and human umbilical vein, three kinin B1 receptor systems. Moreover, this
      compound was inactive against the effects induced by noradrenaline, 5
      hydroxytryptamine, endothelin-1, angiotensin II, substance P, acetylcholine, and
      histamine in the B2 receptor preparations. Taken together, these results
      demonstrate that FR 173657 is the first potent nonpeptide B2 receptor antagonist
      with high affinity, selectivity, and specificity for kinin B2 receptors of
      different species, including man.

PMID- 9276137
TI  - Kinin receptors in the diabetic mouse.
AB  - It has been proposed that kinins are important inflammatory mediators involved in
      the pathogenesis of several diseases. In the present study, we attempted to
      determine the effects of kinins in a type I diabetic mouse model, using in vitro
      assays. Injection of streptozotocin (STZ) to the C57BL/Ks mdb mice causes an
      insulitis (inflammation of Langerhans islets) that leads to the diabetic
      condition. Ten days following the STZ treatment, the mice showed increased
      glycemia. We examined the effect of kinins and other agents (substance P,
      neurokinin A, acetylcholine) on the stomach fundus and urinary bladder of control
      and diabetic mice. Our results show that the sensitivity of the stomach fundus to
      bradykinin (BK) and desArg9BK (DBK), but not to other contractile agents, was
      substantially increased in the tissues of diabetic mice. The maximal contractions
      induced by BK and DBK were increased 1.5- to 2-fold in the stomachs from diabetic
      mice compared with those from normal mice. BK induced similar maximal
      contractions of urinary bladder strips from normal or STZ-treated mice, while DBK
      did not show any effect on this preparation. Interestingly, the apparent
      affinities of all agonists are similar in the two groups, normal and diabetic.
      These results suggest that B1 and B2 receptors are overexpressed in the stomach
      fundus but not in the urinary bladder of diabetic mice.

PMID- 9276138
TI  - Neurokinin-receptor antagonists: pharmacological tools and therapeutic drugs.
AB  - The mammalian tachykinins (substance P, neurokinin A, and neurokinin B) are
      widely distributed throughout the central and peripheral nervous systems, where
      they act as neurotransmitters or neuromodulators. Historically, the tachykinins
      have been implicated in a wide variety of biological actions such as pain
      transmission, neurogenic inflammation, smooth muscle contraction, vasodilation,
      secretion, and activation of the immune system. Their effects are mediated via
      specific G-protein-coupled receptors (NK1, NK2, and NK3 receptors). The
      development of nonpeptide receptor antagonists revealed species differences in
      neurokinin-receptor pharmacology, and the recent cloning of human neurokinin
      receptors has led to development of compounds with optimized affinity for the
      human target receptor. The neurokinin-receptor antagonists have been used in
      preclinical experiments to confirm the physiological roles of the tachykinins.
      Importantly, it is now recognised that these agents can inhibit the actions of
      tachykinins released from peripheral nerves, and for the NK1-receptor antagonists
      (the most widely studied class of neurokinin-receptor antagonists) central sites
      of action have also been demonstrated. These studies support the development of
      neurokinin-receptor antagonists as potentially exploitable drug therapies in
      humans, particularly in the treatment of pain and emesis.

PMID- 9276140
TI  - Oral activity of peptide bradykinin antagonists following intragastric
      administration in the rat.
AB  - This study has investigated the oral activity, following intragastric
      administration, of three potent and long-acting peptide-based bradykinin
      antagonists, HOE-140, B9430, and CP-0597, in the anesthetized rat, using
      bradykinin-induced hypotension. Two of the three bradykinin antagonists, B9430
      and HOE-140, but not CP-0597, were found to be active following intragastric
      administration, producing dose-dependent (1, 3, and 10 mg/kg) and selective
      inhibition of bradykinin-induced hypotension. At a dose of 10 mg/kg, the
      inhibition of bradykinin-induced hypotension occurred within 15 min and lasted
      for at least 2 h, which was the duration of the experiment. HOE-140 and CP-0597,
      10 micrograms/kg i.v., produced significant inhibition of bradykinin-induced
      responses that lasted for 60 min. B9430, 10 micrograms/kg i.v., produced a
      significantly greater inhibition than HOE-140 and CP-0597, this inhibition being
      significant for the duration of the experiment (2 h) compared with saline
      controls. Considering the close chemical structure of CP-0597 compared with HOE
      140 and B9430, it is not clear as to why CP-0597 was inactive via the
      intragastric route. This is the first demonstration of the oral activity of
      peptide-based bradykinin antagonists following intragastric administration in the
      rat.

PMID- 9276139
TI  - Characterization of FR173657, a novel nonpeptide B2 antagonist: in vitro and in
      vivo studies.
AB  - Bradykinin (BK) is involved in different pathophysiological conditions, including
      allergic and (or) inflammatory reactions. Thus, BK antagonists are considered as
      a potential drug in allergic and (or) inflammatory diseases. Orally active BK
      antagonist would be desirable for this purpose. Here, we describe the
      pharmacological characterization of FR173657 ((E)-3-(6-acetamido-3-pyridyl)-N-[N
      [2,4-dichloro-3-[(2-methyl-8- quinolinyl)oxymethyl]phenyl]-N
      methylaminocarbonylmethyl]acr ylamide) obtained from our screening for
      nonpeptide, orally active B2 antagonists. (i) FR173657 antagonized [3H]BK binding
      with IC50 values of 4.6 x 10(-10) and 8.6 x 10(-9) M in membrane preparations of
      guinea pig ileum and lung, respectively. FR173657 inhibited [3H]BK binding to
      A431, W138, and IMR90 cell lines of human origin with IC50 values of 2.0 x 10(
      9), 2.3 x 10(-9), and 1.7 x 10(-9) M, respectively. FR173657 did not affect
      [3H]des-Arg10-kallidin (B1 ligand) binding onto IMR90 cells. (ii) FR173657
      inhibited guinea pig ileum contractions by BK (6 x 10(-8) M) with an IC50 value
      of 6.1 x 10(-9) M. Acetylcholine- and histamine-induced contraction of guinea pig
      ileum was unaffected by FR173657. (iii) Oral administration of FR173657 dose
      dependently inhibited BK (5 micrograms/kg) and dextran sulfate (activator of
      kinin-kallikrein cascade) induced bronchoconstriction with ED50 values of 0.075
      and 0.057 mg/kg, respectively. In conclusion, FR173657 is a selective potent,
      orally active B2 receptor antagonist that can be used to investigate the role of
      BK in allergic and inflammatory diseases.

PMID- 9276141
TI  - In vitro studies of a bradykinin B1/B2 antagonist linked to a human neutrophil
      elastase inhibitor; a heterodimer for the treatment of inflammatory disorders.
AB  - Inflammatory disorders typically have a complex etiology and involve a multitude
      of inflammatory mediators, and hence, a polytherapeutic approach to these
      diseases would seem appropriate. In certain chronic inflammatory conditions, we
      believe that bradykinin (BK) and human neutrophil elastase (HNE) are
      cooperatively involved. We have previously synthesized compounds with inhibitory
      activity toward both the BK B2 receptor and HNE. The present study describes
      single compounds designed to incorporate HNE inhibitory activity and BK B1 and B2
      antagonist activity. A proprietary HNE inhibitor (HNEI, CP-955) was directly
      linked via amide bond formation to a peptide-based combined BK B1/B2 antagonist
      (B-9430). Three compounds were made using different linking positions in the
      antagonist peptide. For all compounds, B1 and B2 receptor binding in human cloned
      receptors was at least 10-fold less than that of B-9430, whereas in the in vitro
      guinea pig ileum B2 receptor functional assay, the compounds had potencies
      equivalent to B-9430. Compound I was found to have a fourfold increase in HNEI
      activity compared with CP-955, whereas compounds II and III were inactive. These
      data clearly demonstrate that it is possible to retain BK B1/B2 receptor
      antagonist and HNE activity in a heterodimer.

PMID- 9276142
TI  - Modulation of noradrenaline release by B1 and B2 kinin receptors during metabolic
      anoxia in the rat isolated atria.
AB  - A model of metabolic anoxia was used to investigate the modulatory effect of
      bradykinin (BK) on the release of noradrenaline (NA) in isolated rat atria. Atria
      were isolated from Wistar rats and inserted into a perfusion system. After an
      equilibration period of 20 min, the perfusate was collected every 5 min for a
      period of 85 min, during which the atria were field stimulated (5 Hz, 2 ms, 50
      mA, 60 s) at 10 (S1) and 75 (S2) min. The metabolic anoxia was started 40 min
      before S2 by replacing O2 with N2 and by removing glucose. The drugs were added
      20 min before S2, and their effects on NA release were assessed by the ratio
      S2/S1. The spontaneous and electrically stimulated induced (S-I) releases of NA
      were significantly increased by the anoxic procedure. BK (30 nM) significantly
      increased the S-I release of NA under normoxic conditions. However, under anoxia,
      BK had no effect on the S-I release of NA but inhibited its spontaneous release.
      BK coadministered with HOE-140 (100 nM), a B2 receptor antagonist, significantly
      increased the S-I release of NA during anoxia, whereas the coadministration of BK
      with Leu3-des-Arg9-BK (100 nM), a B1 receptor antagonist, significantly inhibited
      that release. Administration of des-Arg9-BK (100 nM) had no effect on the S-I
      outflow of NA following anoxia, although its coadministration with a B1
      antagonist resulted in a significant inhibition of the S-I outflow of NA. The
      present results suggest that BK inhibits NA release through the activation of a
      B2 receptor following a 40-min period of metabolic anoxia. Because this
      inhibition can be observed only in the presence of a B1 receptor antagonist, this
      could imply that B1 receptor activation, revealed by the anoxia, is involved in
      the facilitation of NA release.

PMID- 9276143
TI  - Paradoxical action of desipramine on the modulatory effect of bradykinin on
      noradrenaline release in a model of metabolic anoxia in rat isolated atria.
AB  - We have previously shown that bradykinin (BK) can modulate the release of
      noradrenaline (NA) in a model of metabolic anoxia in the rat isolated atria. In
      this study, we tested the effect of an inhibitor of NA reuptake, desipramine, on
      the modulatory action of BK on NA release in this experimental model. Atria were
      isolated from Wistar rats and inserted into a perfusion system. After an
      equilibration period of 20 min, the perfusate was collected every 5 min for a
      period of 85 min, during which the atria were field stimulated (5 Hz, 2 ms, 50
      mA, 60 s) at 10 (S1) and 75 (S2) min. Desipramine (1 microM) was present
      throughout the experimental procedures. The metabolic anoxia was started 40 min
      before S2 by replacing O2 with N2 and by removing glucose. The drugs were added
      20 min before S2, and their effects were assessed by the ratio S2/S1. The
      spontaneous release of NA was not changed by the anoxic procedure, which
      significantly increased the electrically stimulated induced (S-I) release of NA.
      BK (30 nM) significantly increased the S-I release of norepinephrine under
      normoxic conditions. However, following anoxia, both BK and the B1 receptor
      agonist des-Arg9-BK (100 nM) significantly inhibited the S-I release of NA. The
      inhibition induced by BK was prevented by selective antagonists for B1 and B2
      receptors. These observations contrast with the results obtained without
      desipramine, where BK, but not des-Arg(9)-BK, inhibited the S-I release of NA
      during anoxia. Therefore, blockade of NA reuptake during metabolic anoxia appears
      to alter the modulatory effect of kinins on NA release via the B1 receptor in the
      rat isolated atria.

PMID- 9276145
TI  - Afferent C-fibres release substance P and glutamate.
AB  - Capsaicin is currently used as a specific pharmacological tool for investigation
      of functions of primary afferent C-fibres. Their peripheral terminals play an
      important role in "neurogenic inflammation," mediated by released substance P and
      calcitonin gene related peptide, whereas in the mediation of central functions,
      activation of the N-methyl-D-aspartate (NMDA) receptors has recently been
      demonstrated. A method for continuous monitoring of glutamate concentration was
      used to study mechanisms of capsaicin-induced glutamate release from rat spinal
      cord slices. Both capsaicin and substance P released glutamate from spinal dorsal
      horns in a concentration-dependent manner (EC50 = 0.53 +/- 0.07 and 0.37 +/- 0.06
      microM, respectively). The NMDA antagonist MK-801 (10 microM) had no effect on
      evoked glutamate release, whereas the tachykinin (NK-1) antagonist CP-99994 (10
      microM) reduced responses to both stimuli (p < 0.001). In capsaicin-desensitized
      rats, evoked glutamate release from dorsal horns was significantly decreased yet
      not completely abolished. Although the evoked glutamate release from ventral
      horns was markedly smaller than that from dorsal horns, the normalized responses
      to capsaicin and to substance P were similar. This might be explained by smaller
      amounts of mobilizable glutamate in ventral horns. Our findings confirmed the
      ability of capsaicin to release glutamate mainly from the afferent C-fibres in
      the spinal cord. The observed effect of exogenous substance P and inhibitory
      action of the NK-1 antagonist indicate facilitation of capsaicin-induced
      glutamate release by coreleased substance P.

PMID- 9276144
TI  - Bradykinin activates R-, T-, and L-type Ca2+ channels and induces a sustained
      increase of nuclear Ca2+ in aortic vascular smooth muscle cells.
AB  - The mechanism(s) fo Ca2+ entry stimulated by bradykinin (BK) and the receptor
      subtype responsible for this effect were examined in human and rabbit aortic
      vascular smooth muscle cells (VSMCs). Using the whole-cell voltage clamp
      technique, BK (10(-6)M) significantly (p < 0.05) increased both T- and L-type
      Ca2+ currents (ICa) in rabbit aortic VSMCs. Using the fura-2 total intracellular
      Ca2+ ([Ca]i) measurement technique, BK (10(-6) M) induced a transient increase of
      [Ca]i followed by a sustained component. Pretreatment of rabbit VSMCs with
      sarcoplasmic reticulum (SR) Ca2+ releaser caffeine (1-5 mM) significantly
      decreased the BK-induced transient increase of [Ca]i without affecting the
      sustained component induced by this hormone. This sustained phase was blocked by
      extracellular application of the Ca2+ chelator EGTA. Using the fluo-3 confocal
      microscopy Ca2+ measurement technique to localize cytosolic ([Ca]c) and nuclear
      ([Ca]n) free Ca2+ distribution, the resting sustained concentration of Ca2+ in
      the cytoplasm of rabbit and human aortic VSMCs was less than that in the nucleus.
      BK (10(-7) M) induced a nonsignificant sustained increase of [Ca]c but
      significant (p < 0.05) sustained increase of [Ca]n that was reversed but not
      prevented by the specific B1 receptor antagonist R126 (10(-6) M) as well as by
      the B2 receptor antagonist R817 (10(-6) M). In both VSMC preparations, the
      specific B1 agonist R211 (10(-9) to 10(-7) M) rapidly induced a nonsignificant
      increase of [Ca]c but a significant (p < 0.05) sustained increase of [Ca]n that
      was prevented but not reversed by the B1 selective antagonist R126 (10(-6) M).
      The sustained increase of [Ca]c and [Ca]n induced by BK and B1 receptor agonist
      was blocked by extracellular application of EGTA. These results strongly suggest
      that B1 and probably B2 receptors are functional in human and rabbit aortic
      VSMCs. BK-induced transient increase of [Ca]i is mainly due to the stimulation of
      T- and L-type Ica as well as to Ca2+ release from caffeine- and ryanodine
      sensitive Ca2+ pools. The sustained component induced by the hormone or the B1
      agonist is mainly nuclear and is due to the stimulation of Ca2+ influx through
      the R-type Ca2+ channels that are present at the sarcolemma and the nuclear
      membranes.

PMID- 9276146
TI  - Transient ischemia inhibits nonexocytotic release of norepinephrine following
      sustained ischemia in rat heart: is bradykinin involved?
AB  - Previous studies have demonstrated that transient ischemia inhibits the release
      of norepinephrine (NE) following a sustained ischemia. However, the mechanism
      underlying this inhibition is unknown. Therefore, this study was designed to
      investigate whether bradykinin (BK) may be involved in the inhibition of NE
      release following ischemic preconditioning. The effects of transient ischemia,
      exogenous BK, and kinin receptor blockers on NE release after a prolonged
      ischemia were tested in the isolated rat heart preparation. Three cycles of 5-min
      ischemia and reperfusion resulted in the reduction of NE release from 115.3 +/-
      14.5 to 51.6 +/- 9.3 pmol.g-1 (p < 0.05) after 30 min of subtotal global
      ischemia. This effect was not prevented by the administration of either Lys
      [Leu8]-des-Arg9-BK (1 mumol.L-1), a B1 antagonist, or HOE-140 (1 mumol.L-1), a B2
      antagonist. Three cycles of 5-min BK or des-Arg9-BK infusion also resulted in a
      dose-dependent inhibition of NE release after 30 min of ischemia. The inhibitory
      effects of BK (1 mumol.L-1) or des-Arg9-BK (0.5 mumol.L-1) were blocked by Lys
      [Leu8]-des-Arg9-BK (1 mumol.L-1), but not by HOE-140 (1 mumol.L-1). The results
      show that transient ischemia and BK protect sympathetic nerve endings in the
      isolated rat heart. The inhibition of NE release by pretreatment with BK is
      mediated by the activation of B1 receptors, whereas preconditioning provided by
      transient ischemia may be mediated by a different, yet unknown, mechanism in the
      rat heart.

PMID- 9276147
TI  - A potent and selective CGRP2 agonist, [Cys(Et)2,7]hCGRP alpha: comparison in
      prototypical CGRP1 and CGRP2 in vitro bioassays.
AB  - The development of highly selective and potent agonists and antagonists is
      critical in evaluating the physiological role(s) of each receptor subtype in a
      peptide family. The existence of at least two calcitonin gene related peptide
      (CGRP) receptor subtypes has been proposed based on the potency of CGRP8-37 to
      antagonize the effect of hCGRP alpha in the guinea pig atrium and the agonistic
      properties of the linear analogue [Cys(Acm)2,7]hCGRP alpha to mimic the effect of
      hCGRP alpha in the rat vas deferens. However, the rather low potency of
      [Cys(Acm)2,7]hCGRP alpha (ED50 = 82 +/- 7.5 nM) to activate the CGRP2 receptor
      subtype limits its usefulness. Accordingly, we investigated various structural
      modifications of this linear analogue in prototypical CGRP1 and CGRP2 in vitro
      bioassays. Among them, replacing the acetaminomethyl moiety (Acm) by an
      ethylamide group, [Cys(Et)2,7]hCGRP alpha demonstrated a high potency to inhibit
      the rat vas deferens twitch response (ED50 = 3.4 +/- 1.2 nM), whereas in the
      guinea pig atrium, this analogue induced only a slight inotropic effect at very
      high concentrations (1 microM). Moreover, [Cys(Et)2,7]hCGRP alpha as well as the
      addition of a tyrosine residue at the N-terminal, [Tyr0,Cys(Et)2,7]hCGRP alpha,
      competed with high affinities for [125I]hCGRP binding in rat brain homogenates
      (IC50 = 0.3 and 0.1 nM, respectively). Taken together, these results suggest that
      [Cys(Et)2,7]hCGRP alpha is a new potent analogue that could prove valuable in
      addressing the functional relevance of the CGRP2 receptor class.

PMID- 9276148
TI  - Effect of neuropeptide Y on bradykinin-induced release of prostacyclin and
      thromboxane from guinea pig perfused lung.
AB  - We have previously reported that neuropeptide Y (NPY) inhibits responses induced
      by various agonists (noradrenaline, vasoactive intestinal peptide, substance P,5
      hydroxytryptamine) in isolated guinea pig trachea. Although the underlying
      mechanisms have not been fully characterized, it was found that the NPY-evoked
      inhibition was specifically expressed with agents for which locally released
      prostaglandins (PGs) are important determinants for their myotropic activity. In
      the present study, we have extended these findings by examining whether NPY was
      capable of regulating the release of prostacyclin and thromboxane A2 induced by
      bradykinin (BK) from naive and ovalbumin-sensitized guinea pig perfused lungs.
      Our results showed that infusion of NPY (0.24 microM) through the lung
      significantly inhibited the release of 6-keto-PGF1 alpha (> 30%) and thromboxane
      B2 (50%) induced by intraarterial administration of BK (3 micrograms) from
      untreated and ovalbumin-sensitized guinea pig perfused lung. However, the
      inhibitory effect of NPY was lost in the immunological production of
      prostaglandins. These results suggest that NPY may act as a regulatory agent of
      the release of cyclooxygenase-derived products by possibly acting on events
      preceding phospholipase A2 activation.

PMID- 9276149
TI  - Peptide and nonpeptide lead discovery using robotically synthesized soluble
      libraries.
AB  - The method of combinatorial synthesis of peptide and nonpeptide libraries on
      solid phase is analyzed and the automation of the mix and divide key step
      described. A set of amino acids leading to a high molecular diversity is proposed
      as well as a number of scaffolds for the preparation of variable polyamide
      libraries. Adequacy of the resin bead quantities to library size and to the ratio
      of the synthesized peptide types is discussed. Examples of the use of capillary
      electrophoresis and of spectroscopic methods (MS, MS/MS, and NMR) for the
      analysis of the library content are given. The iterative deconvolution SURF
      (synthetic unrandomization of randomized fragments) is compared with positional
      scanning and the success of coupling of mixtures evaluated. It is concluded that
      extension of the original mix and divide method and the SURF deconvolution (as
      proposed by Houghten et al. Nature (London), 354: 84-86 1991) to nonpeptide
      libraries affords new leads that can be optimized towards useful therapeutics.

PMID- 9276150
TI  - Epitope tagging and immunoreactivity of the human angiotensin II type 1 receptor.
AB  - Structural analysis of G-protein-coupled receptors has largely been limited to
      photoaffinity labeling and site-directed mutagenesis. This is primarily due to
      the difficulty in the production of antibodies against this class of receptors.
      We were therefore interested in tagging the amino-terminal side of the human
      angiotensin II (AngII) type 1 receptor (AT1) with the FLAG epitope DYKDDDDK.
      Competitive binding experiments with [125I][Sar1,Ile8]AngII revealed that stably
      transfected Chinese hamster ovary (CHO) cells express 37,300 hAT1-FLAG
      receptors/cell with a high affinity of 0.53 nM, comparable with that of the wild
      type hAT1. After photolabeling and solubilization, a significant proportion of
      hAT1-FLAG specifically immunoprecipitated with anti-FLAG M5 and M2 antibodies.
      The immunoprecipitated receptor comigrated on SDS-PAGE with photolabeled wild
      type hAT1. Immunofluorescence studies by FACS scan analysis revealed that 11.9%
      of CHO cells expressing hAT1-FLAG receptor significantly increased their
      fluorescence level as a result of M5 specific reactivity. Western blot analysis
      failed to show any specific interaction between M5 antibody and denatured hAT1
      FLAG receptor. These results demonstrate the efficiency of the epitope tagging
      approach for specific immunoreactivity against AT1 receptor. Appropriate
      refinements of this approach could improve the level of immunoreactivity.

PMID- 9276151
TI  - Tachykinin receptors and intestinal motility.
AB  - Substance P (SP) and neurokinin A (NKA) are synthesized by enteric cholinergic
      motorneurons that project to the longitudinal and circular muscle of the
      mammalian intestine. Thus, acetylcholine, SP, and NKA are the excitatory
      neuromuscular transmitters in the intestine. Tachykinin NK1 and NK2 receptors are
      expressed by smooth muscle cells in most regions of the intestine: the corelease
      of SP and NKA from nerves thus realizes paradigms of tachykininergic
      cotransmission. Examples have been found in which a cooperative model can be
      applied to account for the action of SP-NKA acting at NK1 and NK2 receptors
      (e.g., circular muscle of guinea-pig duodenum), as well as examples in which the
      message produced by activation of the two receptors diverges sharply in producing
      responses that have a markedly different time course and use different effector
      systems (e.g., circular muscle of guinea-pig colon). NK3 receptors are expressed
      on both excitatory and inhibitory motor neurons: indirect contractions (via
      release of acetylcholine and tachykinins) and relaxations (via release of nitric
      oxide) can be evoked in the gut by selective stimulation of NK3 receptors.
      Although a role of NK3 receptors in certain enteric reflexes has been evidenced,
      the importance of this system in mediating hexamethonium-resistant enteric
      transmission appears less important than previously speculated.

PMID- 9276152
TI  - Kinins and their receptors in hyperalgesia.
AB  - Kinins (bradykinin, kallidin) are produced at sites of injury and inflammation
      and serve a critical role in signaling tissue distress as well as organising
      tissue responsiveness to injury. The acute activation and prolonged sensitization
      of fine afferents, to produce pain and hyperalgesia, are important in the
      protective responses that occur to minimize further tissue injury. These effects
      occur via activation of B2 receptors present on sensory neurons, resulting in a
      change of membrane excitability and altered cellular neurochemistry. B2 receptor
      activation of a variety of tissues including postganglionic sympathetic fibres
      stimulates the production of several proinflammatory mediators, including
      prostanoids and cytokines, which interact with kinins and contribute to
      inflammation and hyperalgesia. Increased expression of B1 receptors plays a
      prominent role in inflammatory hyperalgesia, but further characterization of the
      cellular mechanism is required. A role for kinins and kinin receptors in central
      pathophysiologies (trauma, ischemia, infection) needs examination. The evidence
      for modulation of nociception and central pain generation is compelling, as
      central bradykinin administration causes hyperalgesia, whereas B2 antagonists are
      antinociceptive. The basis for these effects should be urgently investigated.
      Such data will add further support to the utilization of bradykinin receptor
      antagonists for the treatment of peripheral and central pain.

PMID- 9276153
TI  - Pharmacological characterization of nociceptin receptor: an in vitro study.
AB  - The newly discovered neuropeptide nociceptin (NC) (alias orphanin FQ) was tested
      for its potential direct effects as well as for its ability to modify the
      electrically evoked contractions in several isolated organs suspended in vitro.
      NC was inactive both as stimulant and as inhibitor of smooth muscle in several
      preparations, whereas it inhibited the contractions induced by electrical field
      stimulation in the mouse vas deferens and guinea pig ileum. NC showed the same
      potency (IC50 = 10 nM) in the two preparations. However, it was significantly
      more effective in the mouse vas deferens (maximal effect -80%) than in the guinea
      pig ileum (maximal effect -50%). The inhibitory effect exerted by NC in the two
      preparations was not affected by naloxone or more selective opioid receptor
      antagonists. Moreover, by truncation of C-terminal sequences, NC fragments were
      designed. These fragments were subsequently tested in the mouse vas deferens and
      in the guinea pig ileum: NC(1-13)-NH2 was the smallest peptide maintaining the
      same efficacy and potency as the natural peptide. Finally, NC-NH2 and its
      fragments NC(1-13)-NH2 and NC(1-9)-NH2 were modified by substituting the
      phenylalanine 1 residue with a tyrosine. These peptides were tested in the guinea
      pig ileum, where they behaved as mixed NC-opioid receptor agonists ([Tyr1]NC-NH2
      and [Tyr1]NC(1-13)-NH2) or as pure opioid receptor agonists ([Tyr1]NC(1-9)-NH2.
      In conclusion, the present paper demonstrated that the electrically stimulated
      mouse vas deferens and guinea pig ileum can be used as a sensitive bioassay for
      studying the pharmacology of NC and related compounds.

PMID- 9276154
TI  - Potent, long-acting bradykinin antagonists for a wide range of applications.
AB  - Actions of bradykinin (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg; BK) are mediated by
      constitutively expressed B2 receptors (which require the full BK peptide chain)
      and by B1 receptors (which require BK (1-8) as ligand) that are induced in
      inflammation. BK has many functions in normal and pathological physiology,
      including initiation of most, if not all, inflammation. BK also evidently
      functions as an autocrine stimulant for growth of small cell lung cancer (SCLC).
      A new group of BK antagonists containing the novel amino acid alpha-(2
      indanyl)glycine (Igl) provides both broad-spectrum and selective antagonists for
      all these functions. As examples, D-Arg-Arg-Pro-Hyp-Gly-Igl-Ser-D-Igl-Oic-Arg
      (B9430) is an extremely potent and long-acting antagonist of both B1 and B2
      receptors, is stable against endogeneous kininase enzymes, and is active in
      various in vivo models, including by intragastric administration. Acylation of
      B9430 with dehydroquinuclidine-2-carboxylic acid (Dhq) gives B9562, a highly
      selective B2 antagonist. In contrast, Lys-Lys-Arg-Pro-Hyp-Gly-Igl-Ser-D-Igl-Oic
      (B9858) is a highly potent and selective B1 antagonist. The dimer of B9430 linked
      at the amino terminus with suberimide is a potent selectively cytotoxic agent for
      SCLC cells. Results with these peptides suggest that a new generation of
      antiinflammatory and anticancer drugs may be at hand.

PMID- 9276156
TI  - Use of differential display reverse transcription--polymerase chain reaction for
      discovery of induced adrenomedullin gene expression in focal stroke.
AB  - Differential display and other techniques such as subtractive library screening
      and representational difference analysis have been developed and widely used for
      novel gene discovery in pathological and specific physiological conditions. In
      the present work, we illustrate the utilization of the differential display
      method for the investigation of the differentially expressed genes in a rat model
      of focal brain ischemia. Adrenomedullin, a recently discovered vasodilator
      peptide, was identified to be upregulated after focal brain ischemia and further
      demonstrated to play a pathophysiological role in exacerbating ischemic damage.
      The data suggest a high potential for the application of mRNA differential
      display, as well as other techniques, for the discovery of novel therapeutic
      targets.

PMID- 9276155
TI  - The kinin B1 receptor: an inducible G protein coupled receptor.
AB  - The B1 receptor, selectively stimulated by des-Arg9 fragments of native kinins,
      has a place in the vast family of G protein coupled receptors. We discuss a
      series of six criteria useful for comparing the B1 receptor with the more
      prominent and studied bradykinin B2 receptor. The B1 receptor has attracted
      interest because it is rapidly upregulated in biological systems following some
      types of tissue injury, notably the injection of bacterial materials to rabbits,
      rats, or pigs. A fast and specific genetic program recruits the expression of
      what we know now to be a G protein coupled receptor in smooth muscle cells,
      endothelial cells, fibroblasts, and a few other cell types. The cytokine network
      has been linked to B1 receptor expression in functional experiments, and this may
      be related to the recent finding of potential cytokine response elements in the
      proposed gene promoter of the human B1 receptor gene. The experimental approach
      of B1 receptor mRNA transcriptional regulation, protein synthesis, and maturation
      is illustrated, based on the biochemical (Northern blot) and functional analysis
      of isolated organs from rabbits injected with bacterial lipopolysaccharide or
      incubated in vitro with or without interleukin-1.

PMID- 9276157
TI  - Partial agonists and full antagonists at the human and murine bradykinin B1
      receptors.
AB  - We developed a functional assay to evaluate the activity of kinin peptides at the
      human and mouse bradykinin (BK) B1 receptors. The photoprotein aequorin expressed
      in 293-AEQ17 cells was used to measure calcium mobilization due to activation of
      the human or mouse B1 receptors by kinin peptides. The B1 agonists des-Arg9-BK
      and des-Arg10-kallidin activated the human receptor (EC50 = 112 and 5 nM,
      respectively), whereas the B1 peptide antagonists des-Arg9,Leu8-BK and des
      Arg10,Leu9-kallidin showed no activation. At the murine receptor, the agonists
      des-Arg9-BK and des-Arg10-kallidin activated the receptor with EC50 values of 39
      and 23 nM, respectively. In contrast, the two peptide antagonists showed
      significant agonism at the murine receptor. Thirty-nine and 44% agonism of the
      mouse receptor was observed with des-Arg9,Leu8-BK (EC50 = 56 nM) and des
      Arg10,Leu9-kallidin (EC50 = 177 nM). Two recently described kinin analogues, [Lys
      Lys0,Hyp3,Igl5,D-Igl7,Oic8,des-Arg9]B K and [D-Arg0,Hyp3,Igl5,D-Igl7, Oic8,des
      Arg9]BK (B9858 and des-Arg9-B9430), failed to agonize the mouse receptor. These
      peptides were potent antagonists of des-Arg10-kallidin- and des-Arg9-BK-induced
      bioluminescence at the cloned human and mouse B1 receptors.

PMID- 9276158
TI  - Aprotinin, an antifibrinolytic drug, attenuates bradykinin-induced permeability
      in conscious rats via platelets and neutrophils.
AB  - Two antifibrinolytic drugs, tranexamic acid (TXA) and aprotinin (APR), are used
      to improve the recovery of patients following cardiac surgery while reducing
      blood loss. Their mechanisms of action have yet to be fully understood. To
      investigate their possible mechanisms of action during cardiopulmonary bypass, we
      examined (i) the effects of TXA and APR on bradykinin (BK) induced vascular
      permeability (VP) in conscious rats, (ii) the roles of platelets and neutrophils
      in this reaction, and (iii) the effects of TXA or APR on BK responses in platelet
      or neutrophil-depleted rats. Evans blue dye (EB) was used as the marker of
      extravasation. The animals were treated with antiplatelet serum for platelet
      depletion or with methotrexate for neutrophil depletion. In normal rats, BK
      increased VP in most tissues. Thrombocytopenia and neutropenia also increased
      basal VP. TXA had no significant effect whereas APR decreased basal VP. In the
      second series of experiments, APR significantly attenuated BK-induced increases
      in VP, whereas TXA was completely ineffective. Platelet depletion did not affect
      BK-induced increases of VP, except for a massive plasma exudation in the lung
      parenchyma. Neutrophil depletion also had no effect on BK-induced increases of
      VP, except for an attenuation in the duodenum. In the third and last series of
      experiments, TXA potentiated the effect of BK in the upper and lower bronchi of
      platelet-depleted rats, compared with the effects of TXA on BK in normal animals,
      except in the lung parenchyma, where TXA blocked the increase of VP induced by
      BK. APR also potentiated the effect of BK in the lower bronchi of platelet
      depleted rats. Overall, the inhibitory effect of APR on the VP induced by BK in
      normal rats was attenuated in platelet-depleted rats. Like TXA, APR blocked the
      increase of VP induced by BK in the lung parenchyma of platelet-depleted rats. In
      neutrophil-depleted rats, TXA did not affect the permeabilizing response to BK.
      In those rats, the inhibitory effect of APR against BK increases of VP was
      attenuated. These results show that the beneficial effect of APR, but not TXA,
      following cardiac surgery may be attributed to the inhibition of plasma exudation
      mediated, in part, by BK. In addition, platelets and neutrophils do not appear to
      be involved in BK-mediated plasma exudation. However, both cell types are
      essential for the regulation of basal VP. Finally, the mechanism underlying the
      protective inhibitory effect of APR on BK-induced increases of VP involves, at
      least in part, platelets and neutrophils, since the inhibitory effect of APR is
      attenuated in thrombocytopenic and neutropenic rats. Both cell types are not
      involved in the action of TXA on VP. Therefore, maintaining platelet and
      neutrophil counts following cardiopulmonary bypass could enhance the protective
      effect of APR.

PMID- 9276159
TI  - Kallikrein gene therapy in newborn and adult hypertensive rats.
AB  - The tissue kallikrein-kinin system has been postulated to play an important role
      in blood pressure regulation. Kallikreins are serine proteinases that release
      potent vasodilating kinin peptides from precursor kininogens by limited
      proteolysis. Our recent studies show that systemic delivery of the human tissue
      kallikrein gene into adult spontaneously hypertensive rats (SHR) results in a
      sustained reduction of blood pressure for several weeks. The goal of this study
      is to evaluate whether early delivery of the kallikrein gene into newborn SHR
      could exert a suppressive effect on blood pressure phenotype during rat growth
      and development. A human tissue kallikrein cDNA construct, under the control of
      cytomegalovirus promoter (CMV-cHK), or vector DNA was injected subcutaneously
      into the necks of 2-day-old SHR. Blood pressures were monitored biweekly from 3
      to 19 weeks by the tail-cuff method. A single injection of the human kallikrein
      cDNA construct caused a significant reduction of blood pressure (n = 6, p <
      0.001) from 11 to 17 weeks after injection compared with control rats receiving
      vector DNA. Intravenous delivery of the human tissue kallikrein gene into adult
      SHR produced blood pressure lowering effects (n = 6, p < 0.001) that lasted for 6
      weeks in male but not in female rats. The expression of human tissue kallikrein
      in rats was identified by reverse transcription polymerase chain reaction
      followed by Southern blot analysis and an ELISA specific for human tissue
      kallikrein. Kallikrein gene delivery did not cause any changes in body weight,
      urine volume, or water intake in the experimental animals compared with the
      control group. No antibodies to either human tissue kallikrein or its DNA were
      detected in rat sera 19 weeks postinjection. These results show that delivery of
      the kallikrein gene at an early stage of life has a protective effect against
      development of hypertension in adult SHR and that gender differences could be a
      factor in kallikrein gene therapy for the treatment of hypertensive disorders.

PMID- 9276160
TI  - Characterization of kininogenase activity of an acidic proteinase isolated from
      human kidney.
AB  - An acidic proteinase was purified from human kidney cortex. The enzyme showed a
      molecular mass of 31 kDa by SDS-PAGE, 36 kDa by gel filtration, and isoelectric
      points of 5.2 and 6.1. The optimum pH for hydrolysis of bovine hemoglobin was
      about 3.5. Reverse-phase HPLC analysis of the incubation mixture of the enzyme
      with human plasma showed the presence of an active peptide on rat uterus muscle
      with the same retention time as the methionyl-lysyl-bradykinin (MLBK) standard.
      The specific activities were 2.91 micrograms MLBK equivalent mg-1.min-1 at pH 3.5
      and 2.15 micrograms MLBK equivalent mg-1.min-1 at pH 6.0. All the enzymatic
      activities of this human kidney proteinase were inhibited by pepstatin A.
      Intramolecularly quenched fluorogenic substrates with amino acid sequences of
      human kininogen were used to determine the cleavage points. On the N-terminal
      sequences (Abz-Leu-Met-Lys-Arg-Pro-Eddnp and Abz-Met-Ile-Ser-Leu-Met-Lys-Arg-Pro
      Eddnp) the cleavage occurred at the Leu-Met linkage, and on the C-terminal
      sequences (Abz-Phe-Arg-Ser-Ser-Arg-Eddnp and Abz-Phe-Arg-Ser-Ser-Arg-Gln-Eddnp)
      the cleavage occurred at the Arg-Ser linkage. Abz-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe
      Arg-Ser-Ser-Arg-Gln-Eddnp++ + was hydrolyzed by the renal acidic proteinase and
      yielded the peptide Abz-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg (Abz-bradykinin).
      Kinectic parameters were determined using Abz-Met-Ile-Ser-Leu-Met-Lys-Arg-Pro
      Eddnp (K(m) = 0.69 +/- 0.08 microM; Kcat = 0.052 +/- 0.0095 s-1; Kcat/K(m) =
      0.075 +/- 0.005 microM-1.s-1) and Abz-Phe-Arg-Ser-Ser-Arg-Gln-Eddnp (K(m) = 1.56
      +/- 0.16 microM; Kcat = 0.0048 +/- 0.0001 s-1; Kcat/K(m) = 0.003 +/- 0.0003
      microM-1.s-1). Human liver cathepsin D had no activity on C-terminal sequences
      and human pepsin hydrolyzed them at the Ser-Ser bond. The results suggest that
      the renal acid proteinase is distinct from human pepsin and human liver cathepsin
      D and releases MLBK from human kininogen.

PMID- 9276161
TI  - Physiologic consequences of training.
AB  - Systematic exercise training results in changes in skeletal muscle that increase
      oxidative capacity and vascular conductance, which lead to an increase in maximal
      A-VO2. Also, maximal cardiac output is increased, largely because of an increase
      in maximal stroke volume. Heart rate is decreased at rest and during submaximal
      exercise because of increased parasympathetic tone and the effect of increased
      stroke volume on reflex sympathetic tone. The increases in maximal A-VO2 and
      cardiac output result in increased maximal VO2, the hallmark of the dynamically
      trained individual. Predominant static exercise training results in fewer
      increases in maximal VO2 and more local muscle strength enhancements. The
      systematic application of cross-training can increase both cardiovascular and
      strength parameters, leading to enhanced athletic performance.

PMID- 9276162
TI  - Mechanics of left ventricular systolic and diastolic function in physiologic
      hypertrophy of the athlete's heart.
AB  - As a result of a number of factors, there is tremendous diversity in the pattern
      of cardiac mechanics encountered in athletes. Nevertheless, several trends can be
      identified, and several conclusions are possible. Hypertrophy of a mild to
      moderate degree and out of proportion to body size is a common finding. Some
      athletes experience ventricular dilation with appropriate hypertrophy and
      preservation of the ventricular mass-to-volume ratio, whereas others manifest
      concentric hypertrophy with an increased mass-to-volume ratio. The functional
      changes that are encountered appear to be secondary to the structural
      alterations, and there is no evidence of altered myocardial systolic or diastolic
      properties. Some athletes with hypertrophy have reduced wall stress when they are
      evaluated at rest, and velocity of shortening is augmented because of the reduced
      afterload. As a result of adaptation to a high-output state, some athletes appear
      preload reduced when evaluated at rest. Although velocity of shortening is not
      affected by preload status, fractional shortening is inversely related to
      preload. The magnitude of systolic shortening is therefore the net result of
      altered preload and afterload and cannot be understood without assessing both of
      these parameters. When the various determinants of systolic shortening are
      included, contractility appears to be normal. There have been several reports of
      depressed contractility immediately after extreme exertion. Although the
      mechanism remains uncertain, several intriguing possibilities have been proposed.

PMID- 9276163
TI  - The morphologic consequences of systemic training.
AB  - The development of echocardiography in the 1970s led to the flourishing of the
      study of the athlete's heart. From the earliest studies, it was apparent that
      athletes develop enlargement of the left ventricular cavity and thickening of
      myocardium in response to prolonged repetitive training. The changes in
      echocardiographic measurements are small and often within quoted normal ranges.
      By comparison to sedentary controls, however, left ventricular end-diastolic
      dimension is increased by approximately 10%, posterior wall dimension by 15% to
      20%, and calculated mass by up to 45%.

PMID- 9276164
TI  - Outer limits of the athlete's heart, the effect of gender, and relevance to the
      differential diagnosis with primary cardiac diseases.
AB  - Two concepts from pathologic descriptions of myocardial hypertrophy in trained
      individuals merit consideration: (1) The heart of the trained athlete can be
      twice the normal size, but histologic structure remains intact, and (2) the
      weight of the trained heart does not usually surpass the limit of 500 g, defined
      as the critical heart weight. Even though this threshold cannot be accepted
      dogmatically, the concept of an upper limit for physiologic cardiac remodeling is
      nevertheless relevant to the clinical question of distinguishing extreme
      expressions of athlete's heart from primary pathologic conditions. This
      morphologic distinction depends on whether the magnitude of cardiac remodeling in
      athletes exceeds that expected as a result of athletic conditioning alone. There
      has also been a great interest in understanding the impact that types of athletic
      conditioning and gender have on defining the upper limits to which such
      physiologic hypertrophy may extend.

PMID- 9276165
TI  - Impact of different sports and training on cardiac structure and function.
AB  - There is overwhelming evidence, particularly from echocardiography, that the
      heart of competitive athletes may differ from that of nonathletes, matched for
      age, gender, and body size. A larger left ventricular mass has been shown in
      athletes performing predominantly dynamic aerobic and anaerobic sports, in
      athletes engaged in static training, and in players of ball sports. Enlargement
      of the left ventricular internal diameter was most pronounced and reached about
      10% in athletes performing predominantly dynamic sports; mainly strength training
      athletes had a lesser increase of the internal dimension, which was limited to
      2.5%. Also the left ventricular wall appeared to be thickened in all types of
      athletes compared with controls. In sports with high dynamic and low static
      demands, wall thickness was proportionate or slightly disproportionate to the
      size of the internal diameter so that relative wall thickness was not different
      from controls or slightly increased (predominantly eccentric hypertrophy). In
      strength athletes, the disproportionate increase of wall thickness averaged about
      12% (predominantly concentric hypertrophy). In sports with high dynamic and high
      static demands and requiring prolonged training, such as cycling, the increases
      of absolute and relative wall thickness reached 29% and 19% and were more
      pronounced than in runners (mixed hypertrophy). A plausible interpretation of
      these results is that the development of so-called eccentric or concentric left
      ventricular hypertrophy according to the type of sports cannot be regarded as an
      absolute or dichotomous concept because training regimens and sports activities
      are not exclusively dynamic or static and because the load on the heart is not
      purely of the volume or the pressure type. Most studies agree that left
      ventricular systolic and diastolic function is normal in the athlete at rest,
      whereas diastolic function seems to be enhanced in the exercising endurance
      athlete. The consistency of the results of studies on athletes in the competitive
      and the resting season, of training of sedentary subjects, and of spinal cord
      injured patients suggests that variations in physical activity can alter left
      ventricular structure; genetic factors do not seem to be involved in the size of
      the left ventricular internal diameter but have to be taken into account to
      interpret wall thickness.

PMID- 9276167
TI  - Loss of cardiovascular adaptations after physical inactivity.
AB  - The main objective of this article is to focus on the loss of cardiovascular
      adaptations after cessation of exercise. A brief description of the nature of
      adaptive changes to chronic exercise is given to provide a background and
      understanding of physiologic mechanisms underlying cardiovascular adaptations to
      exercise training and their clinical implications.

PMID- 9276166
TI  - The power athlete.
AB  - A number of normal daily and athletic activities require isometric or static
      exercise. Sports such as weight lifting and other high-resistance activities are
      used by power athletes to gain strength and skeletal muscle bulk. Static
      exercise, the predominant activity used in power training, significantly
      increases blood pressure, heart rate, myocardial contractility, and cardiac
      output. These changes occur in response to central neural irradiation, called
      central command, as well as a reflex originating from statically contracting
      muscle. Studies have demonstrated that blood pressure appears to be the regulated
      variable, presumably because the increased pressure provides blood flow into
      muscles whose arterial inflow is reduced as a result of increases in
      intramuscular pressure created by contraction. Thus, static exercise is
      characterized by a pressure load on the heart and can be differentiated from the
      hemodynamic response to dynamic (isotonic) exercise, which involves a volume load
      to the heart. Physical training with static exercise (i.e., power training) leads
      to concentric cardiac (particularly left ventricular) hypertrophy, whereas
      training with dynamic exercise leads to eccentric hypertrophy. The magnitude of
      cardiac hypertrophy is much less in athletes training with static than dynamic
      exercise. Neither systolic nor diastolic function is altered by the hypertrophic
      process associated with static exercise training. Many of the energy requirements
      for static exercise, particularly during more severe levels of exercise, are met
      by anaerobic glycolysis because the contracting muscle becomes comes deprived of
      blood flow. Power athletes, training with repetitive static exercise, derive
      little benefit from an increase in oxygen transport capacity, so that maximal
      oxygen consumption is increased only minimally or not at all. Peripheral
      cardiovascular adaptations also can occur in response to training with static
      exercise. Although the studies are controversial, these adaptations include
      modest decreases in resting blood pressure, reduced increases in blood pressure
      and sympathetic nerve activity during a given workload, enhanced baroreflex
      function, increases in muscle capillary-to-fiber ratio, possible improvements in
      lipid and lipoprotein profiles, and increases in glucose and insulin
      responsiveness. Some of these adaptations can occur in cardiac or hypertensive
      patients with no concomitant cardiovascular complications. In both healthy
      individuals and those with cardiovascular disease, the manner in which resistance
      training is performed may dictate the extent to which these adjustments take
      place. Specifically, training that involves frequent repetitions of moderate
      weight (and hence contains dynamic components) seems to produce the most
      beneficial results.

PMID- 9276168
TI  - Causes of sudden death in young and middle-aged competitive athletes.
AB  - The incidence of sudden death in athletes is low. Some pathologic conditions may
      predispose to sudden death during exercise in young athletes. In older
      individuals, exercise may trigger terminal arrhythmias in patients with severe
      coronary atherosclerosis. Screening programs with a history and a physical
      examination are recommended for high school and collegiate sports participants.
      For older individuals who are likely to have undetected or overt coronary heart
      disease and are exercising for physical fitness, caution regarding the level of
      activity and type of symptoms that are frequently associated with coronary
      disease may help prevent sudden death.

PMID- 9276169
TI  - Exercise and its role in sudden cardiac death.
AB  - This article summarizes available population-based data related to the risk of
      sudden cardiac death during exercise and the factors that influence the risk
      among apparently healthy adults in the community. Recent evidence puts into
      perspective the cardiac risks and benefits of exercise. The data suggest that
      although the occurrence of sudden cardiac death during acute bouts of exercise is
      not a chance occurrence, the transient increase in risk is outweighed by the
      cardiac benefits of habitual exercise. The implications of these findings for
      both clinical practice and public health are reviewed.

PMID- 9276170
TI  - Risk profiles and cardiovascular preparticipation screening of competitive
      athletes.
AB  - There has been heightened interest in the design and role of preparticipation
      screening for high school and college athletes. An American Heart Association
      consensus panel, composed of cardiovascular specialists and other physician
      experts having extensive clinical experience with athletes of all ages as well as
      a legal expert, assessed the benefits and limitations of preparticipation
      screening for early detection of cardiovascular abnormalities in competitive
      athletes. The panel addressed cost-efficiency and feasibility issues as well as
      the medicolegal implications of screening; and developed consensus
      recommendations and guidelines for the most prudent, practical, and effective
      screening procedures and strategies.

PMID- 9276171
TI  - Considerations for racial differences in the athlete's heart and related
      cardiovascular disease.
AB  - Athletic training is often associated with modest increases in left ventricular
      chamber size, wall thickness, and mass, which appear to be related to the level
      and intensity of training as well as the type of activity performed. It appears
      that for given levels and types of training, some individuals show more marked
      morphologic changes. It has been speculated that the cardiac alterations that
      occur with athletic conditioning may be due, in part, to genetic factors that
      exist independent of training. Related to this issue is the possibility that
      racial (or biologic) differences in cardiac response to exercise may also exist.
      This article reviews the available data that address racial differences in the
      cardiac response to exercise and to left ventricular pressure overload and the
      implications of these findings.

PMID- 9276172
TI  - The athlete's heart. Historical perspectives--solved and unsolved problems.
AB  - Clinicians are coming back to Henschen's assessment of the athlete's heart as a
      physiologic and positive phenomenon. An athlete's heart may be affected by
      clinical conditions. Regarding the extreme performance of the athlete's heart in
      training and competition, conditions that may be harmless in sedentary people can
      be fatal for the athlete. The athlete's heart therefore deserves the particular
      interest and care of the sports cardiologist.

PMID- 9276173
TI  - GABAergic cell subtypes and their synaptic connections in rat frontal cortex.
AB  - Physiological, morphological and immunohistochemical characteristics of non
      pyramidal cells in frontal cortex of young rats were studied in vitro by whole
      cell recording and biocytin injection. Several groups of GABAergic non-pyramidal
      cells were identified: (i) parvalbumin fast-spiking (FS) cells with low input
      resistances and spikes of short duration, including extended plexus (basket)
      cells and chandelier cells. These cells showed abrupt episodes of non-adapting
      repetitive discharges; (ii) late-spiking (LS) cells exhibiting slowly developing
      ramp depolarizations, including neurogliaform cells; (iii) the remaining groups
      contained both burst-spiking (BS) or regular-spiking (RS) non-pyramidal (NP)
      cells. BSNP cells exhibited bursting activity (two or more spikes on slow
      depolarizing humps) from hyperpolarized potentials. Both these physiological
      types corresponded to a range of morphologies: (i) somatostatin-containing
      Martinotti cells with ascending axonal arbors to layer I (some were also positive
      for calbindin D28k); (ii) VIP-containing double bouquet cells with descending
      axonal arbors as well as arcade cells (these included small cells immunoreactive
      for CCK or calretinin). Each subtype of cells made GABAergic synapses onto
      relatively specific portions of cortical cells, but similar domains were
      innervated by multiple classes of GABA cells.

PMID- 9276174
TI  - Influence of low and high frequency inputs on spike timing in visual cortical
      neurons.
AB  - Cortical neurons in vivo respond to sensory stimuli with the generation of action
      potentials that can show a high degree of variability in both their number and
      timing with repeated presentations as wells as, on occasion, a high degree of
      synchronization with other cortical neurons, including in the gamma frequency
      range of 30-70 Hz. Here we examined whether or not this variability may arise
      from the intrinsic mechanisms of action potential generation in cortical regular
      spiking, fast spiking and intrinsic burst-generating neurons maintained in vitro.
      For this purpose, we performed intracellular recordings in slices of ferret
      visual cortex and activated these cells with the intracellular injection of
      various current waveforms. Some of these waveforms were derived from barrages of
      postsynaptic potentials evoked by visual stimulation recorded in vivo; others
      were artificially created and contained various amounts of gamma range
      fluctuations; finally, others consisted of swept-sinewave current (ZAP current)
      functions. Using such stimuli, we found that, as expected given the resistive and
      capacitive properties of cortical neurons, low frequencies have a larger effect
      on the membrane potential of cortical neurons than do higher frequencies.
      However, increasing the amount of gamma range fluctuations in a stimulus leads to
      more precise timing of action potentials. This suggests that different
      frequencies play different roles, low frequencies being efficient for
      depolarizing cells with high frequencies increasing the precision of action
      potential timing. In parallel to increases in temporal precision, the addition of
      higher frequency components increases the range of interspike intervals present
      in the action potential discharge. These results suggest that higher frequency
      components such as gamma range fluctuations may facilitate the generation of
      action potentials with a high temporal precision while at the same time
      exhibiting a high degree of variability in interspike intervals on single trials.
      This temporal precision may facilitate the use of temporal codes or the
      generation of precise synchronization for the transmission and analysis of
      information within cortical networks.

PMID- 9276175
TI  - Effects of cholinergic modulation on responses of neocortical neurons to
      fluctuating input.
AB  - Neocortical neurons in vivo are spontaneously active and intracellular recordings
      have revealed strongly fluctuating membrane potentials arising from the irregular
      arrival of excitatory and inhibitory synaptic potentials. In addition to these
      rapid fluctuations, more slowly varying influences from diffuse activation of
      neuromodulatory systems alter the excitability of cortical neurons by modulating
      a variety of potassium conductances. In particular, acetylcholine, which effects
      learning and memory, reduces the slow alterhyperpolarization, which contributes
      to spike frequency adaptation. We used whole-cell patch-clamp recordings of
      pyramidal neurons in neocortical slices and computational simulations to show,
      first, that when fluctuating inputs were added to a constant current pulse, spike
      frequency adaptation was reduced as the amplitude of the fluctuations was
      increased. High-frequency, high-amplitude fluctuating inputs that resembled in
      vivo conditions exhibited only weak spike frequency adaptation. Second, bath
      application of carbachol, a cholinergic agonist, significantly increased the
      firing rate in response to a fluctuating input but minimally displaced the spike
      times by < 3 ms, comparable to the spike jitter observed when a visual stimulus
      is repeated under in vivo conditions. These results suggest that cholinergic
      modulation may preserve information encoded in precise spike timing, but not in
      interspike intervals, and that cholinergic mechanisms other than those involving
      adaptation may contribute significantly to cholinergic modulation of learning and
      memory.

PMID- 9276176
TI  - Synaptic interactions in neocortical local circuits: dual intracellular
      recordings in vitro.
AB  - Properties of local synaptic connections in neocortex, studied with dual
      intracellular recordings in vitro and correlated with cell and synaptic
      morphology are summarized. The different durations and sensitivities to somatic
      membrane potential of pyramid-pyramid excitatory postsynaptic potentials (EPSPs)
      apparently reflect the positions of the synapses on the postsynaptic dendrites.
      Their time-, frequency- and voltage-dependent properties enable supra-linear
      summation of several low-frequency inputs arising in the same dendritic region,
      even if only loosely coincident, but they depress during repetitive firing in any
      one input. Pyramidal input to classical fast spiking and low threshold spiking
      interneurones are strikingly different. Here low presynaptic firing rates results
      in many transmission failures. EPSPs are brief and inputs must be near coincident
      for summation. However, these synapses display pronounced. frequency-dependent,
      incrementing facilitation at higher presynaptic frequencies. Once initiated by a
      brief high-frequency burst, this facilitation is maintained at lower frequencies.
      GABAA receptor-mediated inhibitory postsynaptic potentials (IPSPs) arising
      proximally are of very different durations depending on the type of interneurone
      activated and can prevent and subsequently synchronize firing in their many
      postsynaptic partners with very different delays (eg. 10-100 ms). Low threshold
      spiking interneurones, in contrast, generate brief IPSPs only in more distal
      dendritic regions and have little effect on somatic excitability acting to shunt
      input distally.

PMID- 9276177
TI  - A network of tufted layer 5 pyramidal neurons.
AB  - Tufted layer 5 (TL5) pyramidal neurons are important projection neurons from the
      cerebral cortex to subcortical areas. Recent and ongoing experiments aimed at
      understanding the computational analysis performed by a network of synaptically
      connected TL5 neurons are reviewed here. The experiments employed dual and triple
      whole-cell patch clamp recordings from visually identified and preselected
      neurons in brain slices of somatosensory cortex of young (14- to 16-day-old)
      rats. These studies suggest that a local network of TL5 neurons within a cortical
      module of diameter 300 microns consists of a few hundred neurons that are
      extensively inter-connected with reciprocal feedback from at least first-, second
      and third-order target neurons. A statistical analysis of synaptic innervation
      suggests that this recurrent network is not randomly arranged and hence each
      neuron could be functionally unique. Synaptic transmission between these neurons
      is characterized by use-dependent synaptic depression which confers novel
      properties to this recurrent network of neurons. First, a range of rates of
      depression for different synaptic connections enable each TL5 neuron to receive a
      unique mixture of information about the average firing rates and the temporally
      correlated action potential (AP) activity in the population of presynaptic TL5
      neurons. Second, each AP generated by any neuron in the network induces a change
      (defined as an iteration step) in the functional coupling of the neurons in the
      network (defined as network configuration). It is proposed that the network
      configuration is iterated during a stimulus to achieve an optimally orchestrated
      network response. Hebbian, anti-Hebbian and neuromodulatory-induced modifications
      of neurotransmitter release probability change the rates of synaptic depression
      and thereby alter the iteration step size. These data may be important to
      understand the dynamics of electrical activity within the network.

PMID- 9276178
TI  - Physiological properties of inhibitory interneurons in cat striate cortex.
AB  - Physiological and morphological properties of identified interneurons in the
      striate cortex of the cat were studied in vivo by intracellular recording and
      staining with biocytin. In conformity with in vitro studies, these non-pyramidal
      fast spiking cells have very brief action potentials associated with a high rate
      of fall, and a large hyperpolarizing afterpotential. These cells show high
      discharge rates, little or no spike frequency adaptation in response to
      depolarizing current injection, as well as a diverse range of firing patterns.
      Three of the cells were labeled and were found to be aspiny or sparsely spiny
      basket cells, with bitufted or radial dendritic arrangements, in layers II-IV.
      Their axonal arborizations were more dense near their somata and extended
      horizontally or vertically. Of 13 visually responsive cells tested, the receptive
      field properties of six cells and the orientation and direction preferences of
      eight cells were determined. Five of the successfully mapped cells had simple
      receptive fields while one had a complex receptive field type. The orientation
      and direction tuning properties of the overlapping set of eight cells showed a
      broad spectrum ranging from unselective to tightly tuned. The majority exhibited
      a clear preference for orientation and none of the cells were clearly direction
      selective. Quantitative analysis of the temporal properties of the spike trains
      during visual stimulation and spontaneous activity revealed that these cells do
      not exhibit any significant periodic activity, and fired at rates that were well
      below their maximum in response to depolarizing current pulses.

PMID- 9276179
TI  - Functional study of the rat cortical microcircuitry with voltage-sensitive dye
      imaging of neocortical slices.
AB  - The computations performed within cortex are likely to be determined by its
      internal dynamics in addition to its pattern of afferent input. As a step toward
      characterizing these dynamics, we have imaged electrical activity in slices from
      rat primary visual cortex stained with the voltage-sensitive dye di-4-ANEPPS. In
      response to electrical stimulation two fluorescence signals of similar maximum
      amplitude are elicited, (i) A fast signal that peaks in a few milliseconds, is
      dependent on membrane voltage, and has a significant presynaptic component. This
      signal can be used to image electrical activity ratiometrically. (ii) A slow
      signal that peaks a few seconds after stimulation, does not reflect voltage
      changes, and may originate from changes in scattering properties of the slice and
      from interactions of the dye with the cells. The spatial pattern of fast signals
      obtained in response to focal stimulation of coronal slices is consistent with
      known interlaminar projection patterns. In tangential slices, imaging of fast
      signals reveals clustered horizontal responses. Finally, imaging of fast signals
      during epileptiform activation of the disinhibited circuit reveals propagating
      responses, without evidence for modular activation.

PMID- 9276180
TI  - An intracellular study of the contrast-dependence of neuronal activity in cat
      visual cortex.
AB  - Extracellular recordings indicate that mechanisms that control contrast gain of
      neuronal discharge are found in the retina, thalamus and cortex. In addition, the
      cortex is able to adapt its contrast response function to match the average local
      contrast. Here we examine the neuronal mechanism of contrast adaptation by direct
      intracellular recordings in vivo. Both simple (n = 3) and complex cells (n = 4)
      show contrast adaptation during intracellular recording. For simple cells, that
      the amplitude of fluctuations in membrane potential induced by a drifting grating
      stimulus follows a contrast response relation similar to lateral geniculate relay
      cells, and does not reflect the high gain and adaptive properties seen in the
      action potential discharge of the neurons. We found no evidence of significant
      shunting inhibition that could explain these results. In complex cells there was
      no change in the mean membrane potential for different contrast stimuli or
      different states of adaptation, despite marked changes in discharge rate. We use
      a simplified electronic model to discuss the central features of our results and
      to explain the disparity between the contrast response functions of the membrane
      potential and action potential discharge in simple cells.

PMID- 9276181
TI  - Role of the temporal domain for response selection and perceptual binding.
AB  - Most cognitive functions are based on highly parallel and distributed information
      processing by the brain. A paradigmatic example is provided by the vertebrate
      visual system where numerous cortical areas have been described which analyse
      different types of visual information. At present, it is unclear how information
      can be integrated and how coherent representational states can be established in
      such distributed systems. We suggest that this so-called 'binding problem' may be
      solved in the temporal domain. The hypothesis is that synchronization of neuronal
      discharges can serve for the integration of distributed neurons into cell
      assemblies and that this process may underlie the selection of perceptually and
      behaviourally relevant information. We review experimental results, mainly
      obtained in the visual system, which support this temporal binding hypothesis.

PMID- 9276183
TI  - Those elusive molecular diagnostics CPT codes.

PMID- 9276182
TI  - Synchronized activities of coupled oscillators in the cerebral cortex and
      thalamus at different levels of vigilance.
AB  - The cerebral cortex and thalamus constitute a unified oscillatory machine
      displaying different spontaneous rhythms that are dependent on the behavioral
      state of vigilance. In vivo multi-site recordings from a variety of neocortical
      areas and related thalamic nuclei in cat, including dual simultaneous
      intracellular recordings, demonstrate that corticofugal volleys are effective in
      synchronizing fast (20-50 Hz) and low-frequency (< 15 Hz) oscillations in
      thalamocortical networks, characterizing activated and de-afferented states. (i)
      Fast spontaneous oscillations depend on the depolarization of thalamic and
      cortical cells and appear in a sustained manner during waking and REM sleep.
      Corticothalamic neurons, discharging high-frequency (400 Hz) spike-bursts at 30
      40 Hz, are good candidates to synchronize fast oscillations in reentrant
      thalamocortical loops. Weakly synchronized, fast spontaneous oscillations may be
      reset and become robustly coherent after relevant sensory stimuli in waking or
      internal signals during the dreaming state. (ii) During quiescent sleep, the long
      range synchronization of brain electrical activity results from synchronous
      hyperpolarizations in forebrain neurons. The corticothalamic inputs during the
      depolarizing component of the slow oscillation (< 1 Hz) are effective in grouping
      the thalamic-generated sleep rhythms (spindles at 7-14 Hz and delta at 1-4 Hz)
      into complex wave-sequences. These inputs also control the shape of spindles, and
      favor the long-range synchronization and nearly simultaneous appearance of
      spindles. (iii) The cortical control of thalamic activity is also demonstrated in
      spike-wave-seizures developing from sleep patterns. More than half of
      thalamocortical neurons are silent during spike-wave seizures, being tonically
      hyperpolarized, and display IPSPs (closely related to the paroxysmal depolarizing
      shifts of cortical cells) that are determined by the pattern of activities in
      thalamic reticular cells. All these data congruently show the power of cortical
      control upon thalamic oscillators.

PMID- 9276184
TI  - The Epstein-Barr virus in malignant non-Hodgkin's lymphoma of the upper
      aerodigestive tract.
AB  - Sixty malignant non-Hodgkin's lymphomas originating in the upper aerodigestive
      tract have been analyzed for their cytologic type, immunophenotype and
      association with the Epstein-Barr virus (EBV). The majority of these tumors were
      B-cell lymphomas of blastic cytology (78%) with the exception of lymphomas in the
      parotid gland. Large B-cell lymphomas were the most frequent encountered in the
      sinonasal region and Waldeyer's ring. Twelve lymphomas were of T- or T/NK
      (natural killer)-cell lineage. They were in the nasal cavity and the paranasal
      sinuses (4), the tonsil (5), and the oral cavity (3). Epstein-Barr sequences were
      detected in five angiocentric T/NK-lymphomas, one peripheral T-cell lymphoma, one
      lymphoma of lymphomatoid granulomatosis type, one large B-cell lymphoma, and in a
      lymphoroliferative disorder in an HIV-positive patient. These results suggest
      that EBV is not involved in lymphomagenesis of B-cell tumors, but is associated
      with angiocentric T/NK-cell lymphoma in the upper aerodigestive tract.

PMID- 9276185
TI  - Comparative analysis of detection systems for evaluation of PCR amplified
      immunoglobulin heavy-chain gene rearrangements.
AB  - Four different detection systems were compared for evaluation of polymerase chain
      reaction (PCR) amplified immunoglobulin heavy-chain gene rearrangements in acute
      lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL) of B-cell lineage.
      In 63.0% of the fragments detected by ethidium bromide stained agarose gel
      electrophoresis (Agarose-EtBr) the sensitivity was insufficient to separate the
      specific clonal population from the background of normal B cells. Using
      polyacrylamide gel electrophoresis (PAGE), PAGE combined with single-strand
      conformation polymorphism (PAGE-SSCP) and PhastGel-SSCP (Phast-SSCP) analysis
      with silver staining, the resolution was improved and the majority of the
      inconclusive amplicons were elucidated. However, Phast-SSCP displayed a slightly
      higher detection level compared to PAGE and PAGE-SSCP. According to our findings
      PAGE-SSCP and Phast-SSCP were superior to agarose-EtBr and PAGE in detecting new
      emerging clones and clonal evolution.

PMID- 9276186
TI  - Obtaining clone-specific primer and probe for the immunoglobulin heavy-chain gene
      from paraffin-embedded tissue of B-cell lymphoma: technical considerations.
AB  - The complementarity determining region (CDR) III of the immunoglobulin heavy
      chain (IgH) gene is a tumor-specific marker for B-cell malignancies that has been
      widely exploited for the monitoring of minimal residual disease in B-precursor
      acute lymphocytic leukemia. There are a number of technical problems in applying
      the same technology for B-cell non-Hodgkin's lymphoma (B-NHL). Several procedures
      have been useful in overcoming these unique problems encountered in obtaining the
      tumor-specific sequence of the IgH-CDRIII in B-NHL, including the use of
      denaturing gradient gel electrophoresis or micromanipulation of tissue sections
      in separating the tumor-specific CDRIII products from those of contaminating
      normal B-lymphocytes. Minor modifications of a commercial kit greatly improve the
      purity of the polymerase chain reaction (PCR) products for sequencing.
      Modifications of the 5'-ends of the VH and IH primers, coupled with the cycle
      sequencing technique, make it possible to obtain unambiguous sequences on direct
      sequencing of short PCR products. Computer informatics and programs that
      facilitate the design of tumor-specific primers and probes from CDRIII sequences
      are described.

PMID- 9276187
TI  - PCR analysis of IgH and BCL2 gene rearrangement in the diagnosis of follicular
      lymphoma in lymph node fine-needle aspiration. A critical appraisal.
AB  - In order to improve the cytomorphologic diagnosis of malignant lymphoma on lymph
      node fine-needle aspiration (FNA), and to make a confident discrimination between
      low-grade follicular non-Hodgkin's lymphoma (NHL) and lymphoid hyperplasia,
      polymerase chain reaction (PCR) analysis was performed of the Ig CDR3 region and
      BCL2 breakpoint region in 25 nonselected cases of malignant lymphoma (17 NHL and
      8 Hodgkin's disease [HD]) with histologic control, and 22 cases of lymph nodal
      hyperplasia with histologic and/or clinical control. Among lymphomas, IgH
      monoclonality was detected in 7 (77%) of 9 NHLs and BCL2 rearrangement in 3
      (17.6%) of 17 NHLs, all of which were follicular centroblastic-centrocytic
      (FCBCC). Three BCL2/JH negative FCBCC cases were monoclonal for CDR3. Neither IgH
      monoclonality nor BCL2 rearrangement were found in HD. Among cytologically
      diagnosed lymphoid hyperplasias, one IgH polyclonal case was considered false
      negative, being histologically diagnosed as lymphoplasmacytic NHL on the
      subsequent excisional biopsy. Another 4 cases (2 BCL2 rearranged and 2 monoclonal
      for IgH) were considered false-positive on the basis of histologic features or
      clinical control. These data indicate that the combined PCR analysis of IgH and
      BCL2 rearrangements can confirm a cytologic diagnosis of lymphoma in FNAs while,
      due to the occurrence of both false-positive and false-negative results, it is of
      limited value in the distinction between follicular lymphoma and lymphoid
      hyperplasia without morphologic or clinical support.

PMID- 9276188
TI  - A five-year experience with fragile X testing. Setting laboratory standards of
      practice and a cost-effective protocol.
AB  - During the years 1990-1994, our center tested 652 patients, with a broad range of
      referral indications, for fragile X syndrome using either cytogenetic analysis
      alone (Protocol 1) or more recently, a combination of DNA analysis and routine
      karyotyping (protocol 2). The overall positive rate for fragile X was 3.1% with
      an incidence of other chromosomal abnormalities (OCAs) of 3.2%. Breakdown of
      cases using each testing protocol along with percent positives is: [table: see
      text] Use of Protocol 2 yielded only definitive fragile X results, while more
      than half of the "positives" using Protocol 1 were equivocal. Historically this
      has been problematic for both the laboratory and physician since interpretation
      is often dependent on an equally equivocal clinical picture. Protocol 2
      eliminates these diagnostic dilemmas without compromising detection of other
      chromosomal abnormalities, the incidence of which appears to be unaffected by
      testing method used. The overall incidence of OCA of 3.2% underscores the value
      of routine karyotyping in this referral group and likely reflects the phenotypic
      variability of fragile X and its clinical overlap with other chromosomal
      abnormalities. We believe that a fragile X testing protocol combining routine
      karyotyping with definitive molecular technology represents the most cost
      effective diagnostic approach to this clinically challenging patient population.

PMID- 9276189
TI  - Method for the purification of tissue DNA suitable for PCR after fixation with
      Bouin's fluid. Uses and limitations in microsatellite typing.
AB  - Paraffin-embedded tissues are often the only available material to perform
      polymerase chain reaction (PCR)-based analysis in various medical purposes.
      Unfortunately, the use in many countries of acid fixatives such as Bouin's fluid
      limits the use of such a material for molecular analysis. This article reports
      the methodological details of a DNA purification technique from Bouin-fixed and
      paraffin-embedded samples based on a double washing, in an alcohol then in an
      aqueous medium, of the DNA, which enables PCR reactions from this material.
      Comparison of the results with those obtained by organic solvent purification of
      DNA from frozen tissue fragments showed excellent reproducibility in terms of
      detection of an amplification product on agarose gel. However, differences
      between the methods were quite frequently seen in the allelic typing profile of
      microsatellite sequences (CA repeats), either as neo-alleles or by the loss of
      normal alleles in the fixed materials that constitute a limitation in using DNA
      from Bouin-fixed tissue as a substrate for fine allelotyping.

PMID- 9276190
TI  - Increased sensitivity of in situ hybridization: implications for in situ
      amplification.

PMID- 9276191
TI  - Myeloperoxidase mRNA analysis in acute lymphoblastic leukemia.

PMID- 9276193
TI  - Dopamine neurotransmission and treatments for Parkinson's disease in the
      molecular biology era.
AB  - The study of dopamine neurotransmission has seen remarkable progress during the
      past quarter of a century. However, new problems keep arising as more is learned
      from biochemical analytical studies, necessitating even more detailed
      investigation in order to understand the relationship between dopamine
      neurotransmission and motor functions. For better treatment of Parkinson's
      disease, it is important to solve these problems.

PMID- 9276194
TI  - Polymorphism of dopamine receptors and transporter genes in neuropsychiatric
      diseases.
AB  - The advances made in studies on the molecular biology of the dopamine transporter
      (DAT) and receptors (D1, D2, D3, D4 and D5) are reviewed, and their
      pharmacological characteristics and the relationship between polymorphic
      variations of these human proteins and neuropsychiatric disorders are discussed.
      Data from four studies on the variants of the D2 receptor gene (Ser311-->Cys).
      BalI polymorphism in D3, 48-base repeat polymorphism in D4, and 40-base repeat
      polymorphism in the DAT gene in patients with schizophrenia, mood disorder,
      neurological disease and controls are reported.

PMID- 9276195
TI  - Nigrostriatal dopamine system may contribute to behavioral learning through
      providing reinforcement signals to the striatum.
AB  - The nigrostriatal dopamine system has long been regarded to play an essential
      role in motor mechanisms, since selective damage to this system results in the
      severe motor disturbances known as Parkinson's syndromes. The mechanisms how the
      nigrostriatal dopamine system plays a part is still not clear. Based on recording
      of single neuron activity in the primate striatum and selective destruction of
      the nigrostriatal dopamine system, we propose that this system is crucially
      involved in behavioral learning through providing reinforcement signals to the
      striatum during behavioral learning. The way of involvement in learning seems to
      be consistent with the reinforcement learning rule.

PMID- 9276196
TI  - Differential therapeutic effects of dopamine D1 and D2 agonists in MPTP-induced
      parkinsonian monkeys: clinical implications.
AB  - L-DOPA, the precursor of dopamine, remains most effective in the treatment of
      patients with Parkinson's disease, but prolonged L-DOPA treatment often produces
      adverse effects, including dyskinesia and psychosis. Dopamine receptors can be
      divided into two major subtypes, D1 and D2. Might both subtypes of the dopamine
      receptor be equally relevant to amelioration of parkinsonian symptoms and
      responsible for the adverse side effects? To address this question, the effects
      of D1 or D2 receptor agonists alone and in joint administration were examined in
      MPTP-induced parkinsonian monkeys. The parkinsonian symptoms, such as tremor,
      bradykinesia and rigidity, and the adverse side effects, such as hyperactivity
      and aggressiveness, were evaluated independently using different behavioral
      criteria. The results showed that antiparkinsonian effects can be exerted either
      by the D1 agonist (SKF 82958) alone or by the D2 agonist (quinpirole) alone,
      whereas hyperactivity and aggressiveness manifested by dopamine agonists require
      coactivation of the D1 and D2 receptors. Thus, the antiparkinsonian effect can be
      dissociated from the adverse effect by therapeutic strategy. It is implied that
      imbalances in activation of the D1 and D2 receptors may provide a favorable
      approach for long-term treatment of parkinsonian patients with dopamine drugs.

PMID- 9276197
TI  - Nine-year follow-up study of bromocriptine monotherapy for Parkinson's disease.
AB  - A 9-year nationwide study of bromocriptine monotherapy and combination therapy
      with bromocriptine and levodopa in Parkinson's disease is reported. Eleven
      patients were on bromocriptine monotherapy, 35 patients were on combined
      treatment of bromocriptine and levodopa for a certain time during a 9-year
      period. Maintenance doses of bromocriptine at the end of the 9th year in the two
      groups were 11.1 mg/day in the monotherapy and 12.7 mg/day in the combination
      therapy group with levodopa. Changes in Hoehn and Yahr's grading between the time
      of trial start and the end of 108 months' treatment revealed that 5 of 11 cases
      in the monotherapy group remained in the same stages, the other 2 cases improved
      in condition from stage II to I, and another 4 deteriorated compared with
      pretreatment grade. On the other hand, 20 of 35 cases in the combination-therapy
      group reached more advanced stages, 3 patients moving to stage V. Four of them,
      however, improved, and 11 did not change at the end of 9 years of treatment.
      Although it is difficult to prove the neuroprotective effect of a dopamine
      receptor agonist, our long-term nation-wide collaborative studies will help us to
      answer the question of how bromocriptine works in pharmacokinetic aspects.

PMID- 9276198
TI  - Familial juvenile parkinsonism.
AB  - Some cases of parkinsonism without Lewy bodies were detected, although the
      presence of Lewy bodies is a diagnostic criterion for PD. Thereafter, similar
      cases were repeatedly encountered by researchers at Juntendo University, Tokyo.
      Groups in Niigata and Hiroshima also reported cases of parkinsonism without Lewy
      bodies, which suggests that such cases occur frequently in Japan. Clinically,
      most of these are cases of typical juvenile parkinsonism (JP) and have sufficient
      response to levodopa therapy. Diurnal motor fluctuations were mentioned in some
      reports. The clinical findings vary slightly from case to case but the primary
      pathological finding is restricted to the substantia nigra. Therefore, JP almost
      certainly results from a dopamine deficiency in the nigrostriatal system.
      However, the absence of Lewy bodies raises the possibility of differences in the
      degenerative process from a general pathology of the substantia nigra with the
      Lewy bodies. Many cases without Lewy bodies are familial cases with autosomal
      recessive (AR) inheritance. Both factors may be integrated in a single disease
      although this is still uncertain. Families in which JP appeared to be inherited
      in an autosomal dominant (AD) manner as well as those in which it appeared to be
      inherited in an AR manner were identified. The onset ages of the probands were
      slightly higher in the former than in the latter families. The age of onset in AD
      inheritance family cases may coincide with an age of onset of typical JP due to
      anticipation of the disease. The sporadic cases, which account for half of the JP
      cases, require further analysis.

PMID- 9276199
TI  - Clinical features of familial diffuse Lewy body disease.
AB  - We present 5 patients from two families with familial autosomal dominant diffuse
      Lewy body disease. All 5 patients initially showed parkinsonian symptoms that
      responded well to levodopa therapy; however, dementia followed and later
      progressed. In 3 patients, the disease was manifested before age 40 years,
      exhibiting wearing-off phenomenon and choreic limb dyskinesia. One patient was
      examined neuropathologically, and brain stem lesions compatible with Parkinson's
      disease were revealed, and Lewy bodies and senile plaques were found in the
      cerebral cortex. Familial cases of diffuse Lewy body disease may provide some
      explanation of the pathogenesis of this disease.

PMID- 9276200
TI  - Autosomal dominant familial Parkinson disease: older onset of age, and good
      response to levodopa therapy.
AB  - Autosomal dominant Parkinson's disease in 5 generations of a family living in
      Sagamihara City is reported. Clinical features of this family did not differ from
      common PD, however, neuropathological findings were different from PD. In
      autopsied cases, the loss of melanin-containing cells was mild to moderate, and
      the number of neurons of the locus ceruleus was maintained. No Lewy bodies were
      detected at all from any region where Lewy bodies frequently appear in PD.

PMID- 9276232
TI  - Needleless intravenous systems.

PMID- 9276201
TI  - Analyzer workshop on the treatment of Parkinson's disease.

PMID- 9276233
TI  - Tuberculosis and infection control: what now?

PMID- 9276234
TI  - The cost of selected tuberculosis control measures at hospitals with a history of
      Mycobacterium tuberculosis outbreaks.
AB  - OBJECTIVE: To determine the cost of nonrespirator-related tuberculosis (TB)
      control measures at several hospitals, following publication of the Centers for
      Disease Control and Prevention (CDC)'s revised TB infection control guidelines.
      DESIGN: Infection control (IC) and TB coordinators obtained cost information on
      tuberculin skin-test (TST) programs, addition of IC and employee health service
      (EHS) personnel, and the retrofit or new construction of environmental controls.
      SETTING: Four hospitals with, and one community hospital without, prior
      nosocomial multidrug-resistant TB transmission. RESULTS: During the study period,
      the TST program costs remained constant at four of five hospitals and increased
      at one hospital (median 1994 TST program cost: $5,568; range, $2,393-$44,902).
      Additional IC or EHS personnel were hired at four of five hospitals (median cost
      increase, $125,500; range, $63,000-$228,000). The median cost of new construction
      or new equipment purchases (ie, sputum induction booths, ultraviolet lights, or
      portable high-efficiency particulate air filters) at study hospitals was $163,000
      (range, $45,000-$524,000) and $70,000 (range, $31,000-$93,000), respectively.
      CONCLUSIONS: Costs associated with implementing control measures similar to those
      recommended in the CDC TB IC guidelines varied widely by hospital. Engineering
      controls involved the largest capital outlay, but increases in personnel were the
      largest continuing cost. These costs represent improvements made to upgrade
      selected aspects of hospital TB control programs, not the cost of an optimal TB
      control program.

PMID- 9276235
TI  - Varied approaches to tuberculosis control in a multihospital system.
AB  - OBJECTIVES: To document the actual tuberculosis (TB) control policies and
      procedures in a nonoutbreak setting in a variety of hospitals. To determine if
      any particular practices are linked to higher rates of employee tuberculin skin
      test conversion. DESIGN: Survey of hospital occupational health and infection
      control practitioners for the year 1994 regarding hospital TB policies. Review of
      hospital records to verify the number of patients with TB at each hospital and to
      verify the number of employees with positive tuberculin skin tests. Smoke-stick
      testing of negative-pressure ventilation rooms. SETTING: A 13-hospital health
      system in the Midwest. RESULTS: Hospitals ranged in size from 40 to 1,208 beds
      (median 220) and employed 150 to 6,500 workers (median 875). There were seven
      rural and six urban centers, including four teaching hospitals. All 13 hospitals
      had TB control plans, and all performed annual tuberculin skin testing on
      employees. Annual skin-test positivity rates ranged from 0% to 1.0% (median
      0.3%). Negative-pressure ventilation rooms were available in 11 hospitals. The
      percentage of negative-pressure rooms with effective negative pressure ranged
      from 44% to 100% (median 95%). Three of the 13 hospitals used high-efficiency
      particulate air (HEPA) masks as primary personal respiratory protection, and 8
      used dust-mist or dust-mist-fume masks. We found no relation between the type of
      face mask used, number of functional negative-pressure rooms, or hospital TB risk
      category, and employee skin-test conversion rates. CONCLUSIONS: Considerable
      variation existed in the TB control policies and procedures between hospitals,
      but employee TB skin-test conversion rates were low in all settings.

PMID- 9276236
TI  - Derivation and validation of a pulmonary tuberculosis prediction model.
AB  - OBJECTIVE: To describe the derivation and validation of a pulmonary tuberculosis
      (TB) prediction model that would enable early discontinuation of unnecessary
      respiratory isolation. DESIGN: Patients placed in isolation for suspected
      pulmonary TB were studied retrospectively (derivation cohort) and prospectively
      (validation cohort). Independent predictors of pulmonary TB in the derivation
      cohort (January 1992-March 1994) were identified by retrospective analysis.
      Predictors in the model were assigned weights on the basis of the results of the
      multivariate analysis in order to quantitate the risk of TB in an individual
      patient. The prospective validation consisted of application of the model to
      patients placed in isolation during the period April 1994 to June 1995. The
      predictability of the model in the derivation and validation cohorts was
      evaluated using receiver operating characteristics (ROC), curve analysis, and
      calculation of the area under the ROC curve (AUC). SETTING: A university
      affiliated, urban, public hospital with a large population of prison inmates and
      patients with human immunodeficiency virus infection. INTERVENTIONS: Prospective
      application of the prediction model to patients placed in isolation during the
      validation period. RESULTS: Four factors were found to be independent predictors
      of pulmonary TB among 296 isolation episodes in the derivation cohort; positive
      acid-fast sputum smear (odds ratio [OR], 5.8; 95% confidence interval [CI95], 3.0
      11.0; weight = 3 points), localized chest radiograph findings (OR, 2.5; CI95, 1.3
      4.9; weight = 2 points), residence in a correctional facility (OR, 2.3; CI95, 1.2
      4.4; weight = 2 points), and history of weight loss (OR, 1.8; CI95, 1.0-3.2;
      weight = 1 points). Infection control practitioners applied the model
      prospectively to 220 isolation episodes. The mean (+/-SE) AUCs of the ROC curve
      for the derivation and validation cohorts were not significantly different (.86
      +/- .04 vs .86 +/- .07; P = .90). There was a significant decline in the mean
      duration of isolation from the onset of an automatic TB isolation policy in
      August 1992 to the end of the study (P = .045 by analysis of variance).
      CONCLUSIONS: A pulmonary TB prediction model was derived and validated
      prospectively in a hospital with a moderately high prevalence of TB. The model
      quantitated the risk of TB in an individual patient and aided infection control
      practitioners and primary-care physicians in their decisions to discontinue
      isolation during the validation period. Utilization of the model was responsible,
      in part, for a decrease in the mean duration of isolation during the study
      period. Although the model may not have general applicability due to the
      uniqueness of the patient population studied, this study illustrates how
      prediction models can be developed and used effectively to deal with a clinical
      problem.

PMID- 9276238
TI  - Reduction in tuberculin skin-test conversions among medical house staff
      associated with improved tuberculosis infection control practices.
AB  - OBJECTIVE: To assess the efficacy of an infection control program as measured by
      tuberculin skin-test (TST) conversion rates in medical house staff. DESIGN:
      Observational study. SETTING: University-based hospital in New York City serving
      a large indigent population. PARTICIPANTS: Medical house staff. INTERVENTIONS:
      TST conversions were measured every 6 months in medical house staff from June
      1992 to June 1994. Compliance with the isolation policy was measured by
      identifying room locations 24 hours after admission of patients who had
      Mycobacterium tuberculosis recovered from respiratory specimens. RESULTS: The TST
      conversion rate decreased from 5.8 to 0, 2.3, and 0 per 100 person years of
      exposure in successive 6-month periods. The estimated annual TST conversion rate
      among interns fell from 7 per 100 person years in June 1992 to 0 per 100 person
      years in June 1993 and 0 per 100 person years in June 1994 (P < .029). The
      proportion of patients with pulmonary tuberculosis who were isolated in negative
      pressure rooms increased from 38% to 75% over the study period (P < .01).
      CONCLUSION: Development of a multifaceted infection control program can decrease
      the risk of nosocomial tuberculosis infection in medical house staff.

PMID- 9276237
TI  - Tuberculin skin testing of hospitalized patients.
AB  - OBJECTIVES: We sought to define the prevalence of tuberculin skin test (TST)
      positivity in a group of newly hospitalized patients, to identify risk factors
      for positive tests, and to examine the impact of testing on infection control
      practices. DESIGN: Unblinded cohort study over 5 days in July 1992. SETTING: A
      1,000-bed university-affiliated hospital. PATIENTS: All patients admitted
      (excluding obstetric patients and newborns) were interviewed. Patients without a
      history of tuberculosis (TB) or a positive TST were offered a TST with Candida
      and tetanus controls. RESULTS: Of 346 patients offered the test, 21 (6%) had a
      prior history of TB or a positive TST, and 36 (10%) declined to participate; 279
      of the remaining 289 completed the study. Anergy was demonstrated in 94 (33.7%)
      of 279 patients. New positive TSTs were identified in 19 (10.3%) of 185
      nonanergic patients. Of the 19 TST-positive patients, 6 (32%) had infiltrates on
      chest radiographs and were evaluated for active TB. One patient was treated
      empirically for active TB, and five received isoniazid prophylaxis. Risk factors
      for a new positive TST included age (odds ratio [OR], 1.56 per decade of life; P
      = .021), African American race (OR, 4.81; P = .008), alcohol abuse (OR, 5.53; P =
      .005), and peptic ulcer disease (OR, 4.53; P = .017). Risk factors for anergy
      included admission to a surgical service (OR, 2.1; P = .006), current use of
      steroids (OR, 2.65; P = .005), and human immunodeficiency virus (HIV) infection
      (OR, undefined; P = .034). CONCLUSIONS: Despite a high rate of anergy, routine
      tuberculin skin testing identified a substantial number of patients with TB
      infection who might otherwise have gone unrecognized.

PMID- 9276239
TI  - A pseudo-outbreak of purified protein derivative skin-test conversions caused by
      inappropriate testing materials.
AB  - OBJECTIVE: To investigate a cluster of newly identified tuberculosis infections.
      DESIGN: A field study was conducted including interviews; medical record reviews;
      checking of bills and invoices, pharmacy records, and drug manufacturer
      information; and clinical retesting. SETTING: Community residential facilities
      providing comprehensive services to retarded adults. PARTICIPANTS: Twenty
      residential facility staff (not previously known to be purified protein
      derivative [PPD] positive). RESULTS: Staff had been tested with 250 TU of PPD,
      and 9 of 20 were tuberculin positive. Retesting with 5 TU yielded no reaction.
      CONCLUSIONS: Reactions were attributable to testing with a product not
      recommended for routine PPD screening. Healthcare workers planting PPD Mantoux
      tests always should check the vials to ensure that the appropriate strength
      solution is being used.

PMID- 9276240
TI  - Reduction in tuberculin skin-test conversion rate after improved adherence to
      tuberculosis isolation.
AB  - The rate of purified protein derivative (PPD) conversion in workers at our
      hospital increased to 1.7% in 1991. After implementation of mandatory respiratory
      isolation of patients with community-acquired pneumonia, the rate dropped to
      0.6%. This policy may protect workers in institutions where the majority of
      patients with pneumonia have risk factors for tuberculosis.

PMID- 9276241
TI  - Bleeding after cardiovascular surgery caused by detergent residues in laparotomy
      sponges.
AB  - On 2 successive days in July 1994, six patients who underwent coronary artery
      bypass grafting developed postoperative bleeding requiring reexploration. The
      cause was the use of reprocessed laparotomy sponges with retained detergents,
      inducing a bleeding disorder.

PMID- 9276242
TI  - Effect of treatment on contagiousness of patients with active pulmonary
      tuberculosis.
AB  - In view of the important consequences with regard to policies for respiratory
      isolation of hospitalized patients with active tuberculosis, the duration of
      contagiousness after initiation of effective therapy was reviewed. All relevant
      English-language literature was reviewed to identify in vitro, animal
      experimental, and epidemiological evidence regarding contagiousness of patients
      with active tuberculosis after initiation of therapy. Based on in vitro evidence
      of numbers of tubercle bacilli initially present and rapidity of reduction-with
      therapy, it can be predicted that patients whose respiratory secretions are
      initially smear-negative but culture-positive should no longer have viable
      bacilli detectable by culture within 2 weeks. Based on the same evidence, it can
      be predicted that, after 2 weeks of therapy, almost all smear-positive patients
      will remain culture-positive, and more than one half will remain smear-positive.
      There are few epidemiological studies of this issue, most of which have had major
      methodological weaknesses. None of the results from these studies can be
      considered relevant to the hospital environment, where the majority of workers
      are uninfected and patients are potentially immunocompromised. Animal and in
      vitro evidence suggest that patients with active tuberculosis remain contagious
      at least 2 weeks after the initiation of therapy. Patients with smear-positive
      disease are likely to be contagious much longer. There is no relevant and valid
      epidemiological evidence regarding this issue.

PMID- 9276243
TI  - Infection control issues in construction and renovation.
AB  - Construction or renovation projects in hospitals pose special challenges.
      Infection control personnel should be involved in all phases of these projects to
      ensure that patients, visitors, and staff are protected from unnecessary exposure
      to infectious agents. Infection control personnel must identify the infection
      risks posed by each project and must plan ways to minimize the risk. Infection
      control personnel also must ensure that municipal, county, state, and federal
      infection control guidelines and regulations are met. This article will discuss
      basic infection control issues encountered during construction and renovation,
      offer practical suggestions for addressing these issues, discuss common questions
      that infection control personnel must address, and describe outbreaks related to
      construction and renovation.

PMID- 9276244
TI  - Introduction to the NMR of proteins.

PMID- 9276246
TI  - Protein chemical shifts.

PMID- 9276245
TI  - Double and triple resonance NMR methods for protein assignment.

PMID- 9276247
TI  - Data processing in multidimensional NMR.

PMID- 9276248
TI  - Calculating protein structures from NMR data.

PMID- 9276249
TI  - Studies of protein-ligand interactions by NMR.

PMID- 9276250
TI  - NMR of paramagnetic proteins.

PMID- 9276252
TI  - Metal NMR for the study of metalloproteins.

PMID- 9276251
TI  - NMR studies of peptides and proteins associated with membranes.

PMID- 9276254
TI  - A case history. NMR studies of the structure of a small protein, omega-conotoxin
      MVIIA.

PMID- 9276253
TI  - Production and characterization of recombinant proteins for NMR structural
      studies.

PMID- 9276255
TI  - Spectrometer calibration and experimental setup. Basic principles and procedures.

PMID- 9276256
TI  - Basic cell culture.

PMID- 9276257
TI  - Establishment, maintenance, and cloning of human dermal fibroblasts.

PMID- 9276258
TI  - Aging of cultured human skin fibroblasts.

PMID- 9276259
TI  - Ex vivo maintenance of differentiated mammalian cells.

PMID- 9276260
TI  - Scale-up of suspension and anchorage-dependent animal cells.

PMID- 9276261
TI  - Hollow-fiber cell culture.

PMID- 9276262
TI  - Separation and maintenance of primary T- and B-lymphocytes.

PMID- 9276263
TI  - Human pilosebaceous culture.

PMID- 9276264
TI  - Keratinocyte culture.

PMID- 9276265
TI  - Tissue culture of skeletal muscle.

PMID- 9276266
TI  - Isolation of rat liver hepatocytes.

PMID- 9276268
TI  - Human thyroid epithelial cells.

PMID- 9276267
TI  - Primary kidney cells.

PMID- 9276269
TI  - Derivation and maintenance of embryonic stem cell cultures.

PMID- 9276270
TI  - Culture of cells from human tumors of the nervous system on an extracellular
      matrix derived from bovine corneal endothelial cells.

PMID- 9276271
TI  - Culturing primitive hemopoietic cells. Long-term mouse marrow cultures and the
      establishment of factor-dependent (FDCP-Mix) hemopoietic cell lines.

PMID- 9276272
TI  - Collagen gel culture of the human hematopoietic progenitors CFU-GM, CFU-E, and
      BFU-E.

PMID- 9276273
TI  - Long-term B-lymphoid cultures from murine bone marrow establishment and cloning
      by using stromal cell line AC 6.21.

PMID- 9276274
TI  - Human long-term bone marrow culture.

PMID- 9276275
TI  - In vitro clonal culture of human hematopoietic progenitor cells.

PMID- 9276276
TI  - High proliferative potential colony-forming cells.

PMID- 9276277
TI  - Production of human and murine eosinophils in vitro and assay for eosinophil
      differentiation factors.

PMID- 9276278
TI  - Flow sorting for isolating CFU-E.

PMID- 9276279
TI  - Murine bone marrow-derived macrophages.

PMID- 9276280
TI  - Routine testing of cell cultures and their products for mycoplasma contamination.

PMID- 9276281
TI  - Fluorescent in situ hybridization (FISH) for DNA probes in the interphase and
      metaphase stages of the cell cycle.

PMID- 9276282
TI  - Cytogenetic techniques for human leukemias.

PMID- 9276283
TI  - Visualization of cell replication using antibody to proliferating cell nuclear
      antigen.

PMID- 9276284
TI  - Proliferation of murine myoblasts as measured by bromodeoxyuridine incorporation.

PMID- 9276285
TI  - Analysis of cell proliferation using the bromodeoxyuridine/Hoechst-ethidium
      bromide method.

PMID- 9276286
TI  - mRNA in situ hybridization to in vitro cultured cells.

PMID- 9276287
TI  - Transmission and scanning electron microscope preparation of whole cultured
      cells.

PMID- 9276288
TI  - Adhesion molecules on isolated and cultured microvascular endothelial cells
      demonstrated by immunofluorescence and immune electron microscopy.

PMID- 9276289
TI  - Production of heterologous proteins using the baculovirus/insect expression
      system.

PMID- 9276290
TI  - Transfection and transformation of human thyroid epithelial cells.

PMID- 9276291
TI  - Analyzing chemotaxis using the Dunn direct-viewing chamber.

PMID- 9276292
TI  - Computer-assisted analysis of single-cell behavior.

PMID- 9276293
TI  - Origins and development of peptide antibiotic research. From extracts to
      abstracts to contracts.

PMID- 9276294
TI  - HPLC methods for purification of antimicrobial peptides.

PMID- 9276295
TI  - Strategies for the isolation and characterization of antimicrobial peptides of
      invertebrates.

PMID- 9276296
TI  - Big defensin and tachylectins-1 and -2.

PMID- 9276297
TI  - Tachyplesin and anti-lipopolysaccharide factor.

PMID- 9276298
TI  - Circular dichroism studies of secondary structure of peptides.

PMID- 9276299
TI  - Analytical ultracentrifugation studies of association of peptides.

PMID- 9276300
TI  - NMR characterization of amphipathic helical peptides.

PMID- 9276301
TI  - Laboratory production of antimicrobial peptides in native conformation.

PMID- 9276302
TI  - An approach combining rapid cDNA amplification and chemical synthesis for the
      identification of novel, cathelicidin-derived, antimicrobial peptides.

PMID- 9276303
TI  - Molecular biological strategies in the analysis of antibiotic peptide gene
      families. The use oligonucleotides as hybridization probes.

PMID- 9276304
TI  - Designer assays for antimicrobial peptides. Disputing the "one-size-fits-all"
      theory.

PMID- 9276305
TI  - Interaction of cationic peptides with bacterial membranes.

PMID- 9276306
TI  - The genetic basis of microbial resistance to antimicrobial peptides.

PMID- 9276307
TI  - Assay of antibacterial activities of the bactericidal/permeability-increasing
      protein in natural biological fluids.

PMID- 9276308
TI  - Assay systems for measurement of chemotactic activity.

PMID- 9276309
TI  - Neutralization of the in vivo activity of E. coli-derived lipopolysaccharide by
      cationic peptides.

PMID- 9276310
TI  - Differential display. A general protocol.

PMID- 9276311
TI  - Fingerprinting by arbitrarily primed PCR.

PMID- 9276312
TI  - Differential display using random hexamer-primed cDNA, motif primers, and agarose
      gel electrophoresis.

PMID- 9276313
TI  - Fluorescent differential display.

PMID- 9276314
TI  - Cloning differentially expressed genes by using differential display and
      subtractive hybridization.

PMID- 9276315
TI  - Direct sequencing of differential display PCR products.

PMID- 9276316
TI  - A direct-sequencing-based strategy for identifying and cloning cDNAs from
      differential display gels.

PMID- 9276317
TI  - Differential screening of differential display cDNA products by reverse northern.

PMID- 9276318
TI  - Screening for positive clones generated by differential display.

PMID- 9276320
TI  - RC4D--restriction fragment length polymorphism-coupled domain-directed
      differential display.

PMID- 9276319
TI  - Cloning of the 3' noncoding regions from several members of heat shock protein
      gene families by differential display.

PMID- 9276321
TI  - Identification of immediate-early gene targets of the Raf-1 serine/threonine
      protein kinase using an estradiol-dependent fusion protein, delta Raf-1:ER.

PMID- 9276322
TI  - Isolation of cytokine-inducible genes from hematopoietic cells by differential
      display.

PMID- 9276323
TI  - Hormone-inducible genes in prostate cells.

PMID- 9276324
TI  - Application of differential display in studying developmental processes.

PMID- 9276325
TI  - Identification of novel genes involved in adipose differentiation by differential
      display.

PMID- 9276326
TI  - Isolation of song-regulated genes in the brain of songbirds.

PMID- 9276327
TI  - Identification of vertebrate circadian clock-regulated genes by differential
      display.

PMID- 9276328
TI  - Differential mRNA display. Adaption for in vivo studies of diseased tissues.

PMID- 9276329
TI  - Differential expression of TIMP-3 during neoplastic progression in the mouse JB6
      model system.

PMID- 9276330
TI  - Identification of genes associated with resistance to photodynamic therapy
      mediated oxidative stress.

PMID- 9276331
TI  - RAP-PCR using RNA from tissue microdissection.

PMID- 9276332
TI  - The application of differential display to the brain. Adaptations for the study
      of heterogeneous tissue.

PMID- 9276333
TI  - Analysis of gene expression in hypothalamus in obese and normal mice using
      differential display.

PMID- 9276334
TI  - Expression of an alpha-cardiac like myosin heavy chain in diaphragm, chronically
      stimulated, and denervated fast-twitch muscles of rabbit.
AB  - An additional slow fibre type, type I alpha, is detected in diaphragm and appears
      in fast-twitch hindlimb muscles of rabbit under the influence of altered
      neuromuscular activity. Type I alpha fibres were delineated from fibres
      expressing myosin heavy chain I beta (type I beta) by immunohistochemistry with a
      monoclonal antibody raised against the alpha-cardiac MHCI alpha. When stained for
      mATPase after acid and alkaline preincubations, some type I alpha fibres
      resembled type I beta and type IIA fibres, respectively. Some type I alpha fibres
      displayed dissimilar mATPase staining, indicating heterogeneity of this fibre
      population. The appearance of numerous type I alpha fibres in stimulated muscles,
      which in addition contain type IIA and type I beta fibres, suggested that they
      may be interspaced between types IIA and I beta. Electrophoresis under
      nondenaturing conditions disclosed an additional isomyosin both in normal
      diaphragm and stimulated muscles. This band displayed the same mobility as the
      slowest isomyosin in rabbit masseter muscle. It was recognized by the same
      monoclonal (anti-alpha-cardiac MHC) antibody used for immunohistochemistry.
      Therefore, this isomyosin appeared to be very similar, but perhaps not identical
      to the alpha-cardiac MHC-based isomyosin, probably resulting from discrete
      differences in the MHC complement. This assumption agrees with additional
      findings suggesting an even greater heterogeneity of the MHCs than generally
      assumed. In support of this, we show in atrium and masseter muscles the existence
      of an additional, electrophoretically distinct MHC isoform which migrates in
      close vicinity to MHCI alpha.

PMID- 9276335
TI  - Oestrogen-dependent expression of the SM2 smooth muscle-type myosin isoform in
      rabbit myometrium.
AB  - Ovarectomized rabbits displayed a decreased SM1 to SM2 ratio of smooth muscle
      type myosin heavy chain isoforms compared to unoperated, virgin females which was
      reversed after 17beta-oestradiol administration to a value similar to that of
      control animals. When this steroid was given to sexually immature animals or to
      adult virgin rabbits, SM2 expression was not induced, as also happened with
      proliferating myometrial smooth muscle cells grown in vitro. In growing rabbit,
      the 17beta-oestradiol administration induced the formation of the circular and
      the longitudinal muscle layers, characteristics of sexually competent females.
      The SM2 isoform was up-regulated during postnatal development and the SM1 to SM2
      ratio changed during pregnancy and post-partum period but not with human
      gonadotropin treatment which increases the level of circulating progesterone.
      Immunofluorescence staining of adult myometrium with anti-SM2 antibody indicated
      that this isoform is localized to the longitudinal layer exclusively and, in
      contrast to the circular layer, its expression was independent of oestrogen
      level. Difference in oestrogen sensitivity between the two layers was also
      detected for the expression of the intermediate filament protein vimentin and the
      thin filament protein calponin. Changes of SM2 expression in the myometrium
      correlated with variations in the oestrogen receptor density as also confirmed by
      decreased SM2 content/oestrogen receptor density in the circular layer when
      ovarectomized females were treated with the oestrogen antagonist ICI 182,780. Our
      results indicate that: (1) a specific distribution of myosin heavy chain exists
      within rabbit myometrium, and (2) SM2 myosin expression in this smooth muscle is
      under oestrogen control.

PMID- 9276336
TI  - Evidence for localization of the myotonic dystrophy protein kinase to the
      terminal cisternae of the sarcoplasmic reticulum.
AB  - Myotonic dystrophy is an autosomal dominant multisystem disease primarily
      affecting skeletal muscle and is characterized by the presence of an amplified
      trinucleotide repeat in the 3' untranslated region of the myotonic dystrophy
      protein kinase gene. In this study, the subcellular localization of the myotonic
      dystrophy protein kinase in muscle tissues has been investigated at both
      morphological and biochemical level, by using antibodies against the myotonic
      dystrophy protein kinase. Immunofluorescence studies and Western-blot analysis
      were carried out with antibodies raised against both a synthetic peptide and a
      recombinant fusion protein fragment specific for the myotonic dystrophy protein
      kinase. The kinase is localized both to the surface membranes, and within the
      skeletal fibres in the region of the A-I band boundary. Consistent with the A-I
      location of the kinase is that Western-blot analysis of purified fractions from
      sarcoplasmic reticulum show that triads and sarcoplasmic reticulum terminal
      cisternae are immunoreactive for two myotonic dystrophy protein kinase proteins
      of different molecular weight (85 and 54 kDa). The relative amount of these two
      proteins is different in relation to the muscle type, the 85 kDa protein being
      more evident in skeletal than in cardiac fibres. In addition, immunofluorescence
      studies of cardiac muscle reveal a heavy concentration of DM-PK localized to the
      intercalated discs, as well as a weaker reaction in the sarcoplasm. These results
      taken together suggest that multiple isoforms of the DM-PK may exist and that
      they may be differentially located in muscle tissues.

PMID- 9276337
TI  - Stretch activation and myosin heavy chain isoforms of rat, rabbit and human
      skeletal muscle fibres.
AB  - The underlying mechanism of stretch-induced delayed force increase (stretch
      activation) of activated muscles is unknown. To assess the molecular correlate of
      this phenomenon, we measured stretch activation of single, Ca2+-activated skinned
      muscle fibres from rat, rabbit and the human and analysed their myosin heavy
      chain complement by SDS gradient gel electrophoresis. Stretch activation kinetics
      was found to be closely correlated with the myosin heavy chain isoform complement
      (I, IIa, IId/x and IIb). In hybrid fibres containing two myosin heavy chain
      isoforms (especially IId and IIb), the kinetics of stretch activation depended on
      the percentage distribution of the two isoforms. Muscle fibres of the same type
      but originating from different mammalian species exhibited similar kinetics of
      stretch activation. Considering the differing unloaded shortening velocities of
      these fibres, the time-limiting factors for stretch activation and unloaded
      shortening velocity appear not to be the same. The stretch activation kinetics of
      the fibre types IIB, IID and IIA more likely seemed to follow a Normal Gaussian
      distribution than that of type I fibres. Several type I fibres had
      extraordinarily slow kinetics. This observation corroborates biochemical data
      indicating the possible existence of more than one slow myosin heavy chain
      isoform.

PMID- 9276338
TI  - Characterization of the myosin heavy chains of avian adult fast muscles at the
      protein and mRNA levels.
AB  - High resolution anion-exchange chromatography of myosin subfragment-1 in avian
      fast muscles revealed five fast heavy chains (I-V) expressed in muscle-specific
      patterns. Sequence analysis of a unique peptide established that the proteins
      differed in primary structure and suggested correlation with heavy chain genes
      identified independently by Robbins and coworkers. The identities of the isoforms
      and their expression patterns were confirmed at the mRNA level by a reverse
      transcription, 5'-anchored PCR procedure. The fast white pectoralis major muscle
      possessed heavy chain I, the posterior latissimus dorsi muscle, of similar fibre
      type, expressed heavy chains I, III and IV. The fast red adductor superficialis
      muscle expressed either, or both, of heavy chains II and IV. The lateral
      gastocnemius muscle, of mixed fibre type, expressed heavy chains II-V. In
      general, heavy chains I, III and V appeared to be favoured in fast white fibres,
      while heavy chains II and IV were characteristic of fast red fibres. These
      results imply a greater subtlety of fast muscle function than has previously been
      appreciated.

PMID- 9276340
TI  - Inhibition of mitochondrial calcium uptake slows down relaxation in mitochondria
      rich skeletal muscles.
AB  - Isolated fibres from various muscles were skinned mechanically in oil. From a
      Ca2+-loaded micropipette, local applications of Ca2+ were made. These produced a
      limited contraction which relaxed spontaneously. The time-course of sarcomere
      shortening and re-lengthening was recorded by microcinephotography. Application
      of Ruthenium Red, a potent and specific inhibitor of Ca2+ uptake by mitochondria,
      did not affect the contraction-relaxation cycles of typical glycolytic white
      fibres (frog sartorius, pigeon breast). By contrast, Ruthenium Red greatly slowed
      down the relaxation rate in mitochondria-rich fibres (rat soleus and rabbit
      masseter). In these fibres, Ca2+ uptake by mitochondria seems to play an active
      role in promoting relaxation.

PMID- 9276341
TI  - The fragile X syndrome.
AB  - The currently available data concerning the fragile X syndrome are reviewed in
      this paper. The topics discussed are: (1) the phenotype of the mutation
      (including appearance, behavioural changes and mental retardation) and its
      cytogenetic features, (2) examples and hypotheses of atypical inheritance
      (genetic anticipation, Sherman paradox and X-inactivation-dependent mechanism
      giving rise to this disease), (3) molecular studies (the expansion of the CGG
      repeat as the cause of the instability of the fragile X chromosome), (4) the FMRI
      gene - its possible role, expression and proteins and (5) diagnosis and tests of
      the fragile X syndrome.

PMID- 9276339
TI  - A survey of in situ sarcomere extension in mouse skeletal muscle.
AB  - The giant molecule titin/connectin was demonstrated to connect the ends of thick
      filaments with the Z-disks and thus to provide an elastic connection that seems
      to be responsible for passive tension in striated muscle. To investigate the
      physiological limits of I-band titin extension in skeletal muscle, we have
      measured sarcomere lengths of a number of mouse postural and clonal muscles in
      situ under the constraints imposed by the skeletal, ligamentous and tendinous
      components of the motile apparatus. These values now give upper limits for the
      extension of the I-band and therefore for the maximal degree of titin extension
      under physiological constraints. We find that I-band extension in all muscles
      investigated does not exceed a factor of approximately 2.5 in situ, which is well
      below values obtainable in isolated fibre preparations. Approach to the yield
      point is therefore prevented by extramuscular mechanisms. Sarcomere lengths near
      the tendinous junction and within the muscle are virtually identical in extended
      muscle, suggesting that a major function of titin in intact muscle is to ensure
      uniform sarcomere lengths over the entire muscle length and thus to prevent
      localized myofibril overstretch during isometric contraction.

PMID- 9276342
TI  - Effect of estradiol and progesterone on growth of porcine myometrial smooth
      muscle cells and phospholipase C and adenylate cyclase signalling systems in
      vitro.
AB  - The objective of presented studies was to investigate whether estradiol and
      progesterone administered in vivo and/or added in vitro can influence the primary
      myometrial cell culture and how these steroid hormones can affect hCG stimulated
      cAMP and inositol phosphate production in the porcine uterine myocytes.
      Myometrial smooth muscle cells were obtained from six ovariectomized gilts
      pretreated (n = 4) or not (n = 2) with oestradiol benzoate and progesterone for 5
      consecutive days. Immunocytochemical staining proved that the pattern of
      filamentous actin in the cytoplasm of the myometrial fibroblasts (basketlike
      network) was different from that of myometrial smooth muscle cells (long parallel
      fibres). The myocytes derived from steroid treated pigs and supplemented with
      estradiol and progesterone in vitro formed a hillock pattern on days 4-5 day of
      culture whereas cells obtained from not steroid pretreated gilts were smaller and
      did not create confluent form. Myocytes were treated in vitro with two doses of
      estradiol/progesterone (low - 0.2 nM/50 nM and high - 2 nM/500 nM, respectively)
      and two doses of hCG - 0.1 mU and 1000 mU/ml to study hCG action on the second
      messenger system in myocytes. The myometrial smooth muscle cells treated with low
      dose of estradiol and progesterone in vivo responded with much higher
      accumulation of inositol phosphates to strong (1000 mU/ml) hCG stimulation when
      compared with those receiving high dose of both steroids. The different doses of
      estradiol and progesterone caused a similar increase in basal cAMP accumulation
      as compared to control cells cultured without steroid hormones. hCG (0.1 mU/ml)
      had usually the additive effect on cAMP production in porcine myometrial cells.
      The presented paper shows that estradiol and progesterone administration in vivo
      followed by steroid hormone treatment in vitro affects the primary myometrial
      cells culture and that both steroid hormones modify the basal accumulation of the
      second messengers: cAMP and IP3 and their answer to hCG stimuli in pigs.

PMID- 9276343
TI  - Prenatal development of the human pancreatic islets. Immunocytochemical
      identification of insulin-, glucagon-, somatostatin- and pancreatic polypeptide
      containing cells.
AB  - Histological studies were performed on 24 pancreases of normal human embryos and
      fetuses aged 7 to 38 weeks. For immunocytochemistry, the avidin-biotin-peroxidase
      method was used to identify and localize insulin, glucagon, somatostatin, and
      pancreatic polypeptide (PP) cells. In 7 wk old embryos, cells containing
      somatostatin and PP are observed. One week later appear single glucagon-positive
      cells. In the 9th wk, insulin producing cells are visible. During the fetal
      period two populations of the investigated cells are found: Langerhans islets and
      dispersed cells. The latter cells containing insulin, glucagon or somatostatin
      are localized in the walls of pancreatic ducts throughout the whole gland, while
      PP-positive cells are seen mainly in the part of the pancreas, which develops
      from the ventral anlage (anteroinferior part of the head and adjacent part of the
      main pancreatic duct). During the development of islets we have observed four
      stages: (1) scattered cells (7 to 10 weeks); (2) grouping cells (11 to 15 weeks);
      (3) mantle and zonular islets (10 to 29 weeks), in which B cells located inside
      are surrounded by a thick zone of A, PP and somatostatin-producing cells; (4)
      mixed islets (from 30 weeks on) - all cells are scattered over the whole
      transverse section of the islet. In the developing pancreas, the glucagon- and
      somatostatin-containing cells are the most numerous, while the insulin and PP
      containing cells occur in lesser quantities.

PMID- 9276344
TI  - Distribution of eosinophils along and across successive segments of the rat
      digestive tract: a quantitative study.
AB  - Density of eosinophils stained by substrateless DAB reaction was measured in the
      successive segments and the successive layers of rat digestive tract using a
      semiautomatic computerized image analysis system. The results were calculated in
      a dual way: per area of the entire layer and per area of its connective tissue
      compartment, in which the eosinophils were located (extremely small number of
      intraepithelial and intramuscular eosinophils was not included in the analysis).
      The density of eosinophils in the successive segments of the digestive tract
      seemed to depend primarily on the time of contact between the contents and the
      wall of the segment, being the highest in regions of food/content retention
      (fundus of the stomach, cecum) and the lowest in regions of rapid passage
      (esophagus, pylorus, duodenum). When eosinophil density in the successive layers
      was compared, its gradual decrease in the successive layers (villi>lamina
      propria>submucosa>muscularis) was observed in almost the entire small intestine
      and lower values in submucosa compared to mucosa were also evident in the
      stomach, duodenum and small intestine. It seems that there is a decreasing
      gradient of chemoattractants for eosinophils dependent of the distance from the
      lumen and the contents of the digestive tract. However, this decreasing pattern
      appeared only when the density was calculated for the area of the connective
      tissue compartment suggesting that this method of calculation more reliably
      reflects the distribution of eosinophils and should be used in future
      quantitative studies on tissue eosinophils.

PMID- 9276345
TI  - Lewis lung carcinoma and two transplantable sarcomas in mice as experimental
      therapy models: biological characteristics and cell population kinetics.
AB  - The biological characteristics of three transplantable tumours: two sarcomas
      (SaL, MCA) and Lewis lung carcinoma (LLC) have been studied. We investigated
      histology, DNA ploidy and cell kinetics parameters of the tumours. All examined
      tumours were aneuploid and rapidly proliferating, with the hyperdiploid fraction
      greater than 60%. The SaL tumour was found to have the lowest mean aneuploid
      bromodeoxyuridine labelling index (LI) equal to 21%, while the highest LI of
      35.8% was measured for the LLC tumour. The mean S-phase time was short, lasting
      8.5 - 10.9 hrs. The potential doubling time (T(pot)) assessed by BrdUrd staining
      and flow cytometry were as follows: 37.1 hours for SaL, 22.7 hours for MCA and
      21.4 hours for LLC tumour. The MCA had the shortest volume doubling time (T(d))
      equal to 1.7 days and the longest one, equal to 4.7 days, was found for the LLC.
      The lowest cell loss was found in the MCA tumour (44%), while the highest in the
      LLC tumour (81%). As all the examined tumours proliferate rapidly, there is a
      capacity for accelerated repopulation and therefore the tumours seem to be good
      models for experimental radiotherapy.

PMID- 9276346
TI  - Ultrastructural study of endogenous lipid pneumonia and pulmonary alveolar
      proteinosis coexistent with lung cancer.
AB  - The aim of the study was the ultrastructural analysis of endogenous lipid
      pneumonia (ELP)-type changes localized in the vicinity of primary neoplasms of
      the lungs. The analysis was carried out on the material obtained from 30 patients
      with non-small cell lung carcinoma (NSCLC). Routine histopathological examination
      was performed in light microscope, focusing mainly on the presence or lack of ELP
      type changes. Ultrastructural examinations in transmission electron microscope
      used 12 cases classified among early (4 cases) or advanced (8 cases) ELP forms.
      Results of the study reveal a likely coexistence of ELP- and PAP (pulmonary
      alveolar proteinosis)-type changes in the vicinity of NSCLC and suggest a
      correlation between the processes leading to the development of ELP or/and PAP.
      Ethiopathogenesis of the changes observed and the role of granulocytes,
      macrophages and type II alveolar epithelial cells are discussed.

PMID- 9276347
TI  - Enhanced nucleolar parameters in Vicia faba L. induced by 5-azacytidine may be
      only partly attributed to DNA demethylation.
AB  - We aimed to find if diminishing rDNA expression in differentiating and
      differentiated root parenchyma, in spite of DNA endoreplication, could be related
      to rDNA methylation. The effect of 5-azacytidine (10(-6)M, 72 h) was studied in
      successive segments of Vicia faba roots. In 5-azacytidine-treated cells,
      nucleolar parameters: [3H] uridine incorporation, size, amount of AgNOR protein
      and the number of bi-nucleolate cells were increased. [3H] uridine incorporation
      and the amount of AgNOR protein were significantly correlated. In meristems, HPLC
      analysis demonstrated a decrease in m5dC content by 3.7%. Southern hybridization
      showed demethylation at CCGG sites in repetitive BamHI sequences and discrete
      demethylation in coding region of rDNA.

PMID- 9276349
TI  - Results from the 1995 National College Health Risk Behavior Survey.
AB  - Results from the 1995 National College Health Risk Behavior Survey, which
      monitored health risk behaviors among US college and university undergraduates,
      suggest that many students' behaviors increase their likelihood of adverse health
      outcomes. During the 30 days preceding the survey, 34% of the participants had
      consumed five or more alcoholic drinks on at least one occasion, and 27% had
      drunk alcohol and driven a car. Thirty-one percent had smoked cigarettes
      regularly during their lifetimes, 49% had ever used marijuana, 30% had used a
      condom during their last sexual intercourse, 21% were overweight, and 38% had
      participated in vigorous physical activity on 3 or more of the 7 days preceding
      the survey. These data were analyzed by gender, age group, race and ethnicity,
      and institution type. They can be used by those responsible for the health and
      education of college students to reduce risks associated with the leading causes
      of mortality and morbidity.

PMID- 9276350
TI  - Sorority women's body size perceptions and their weight-related attitudes and
      behaviors.
AB  - Six hundred twenty-seven sorority women were surveyed to determine if sorority
      members constituted a subgroup of college women who may be at increased risk for
      disordered eating. The sorority members were administered Body Mass Index
      Silhouettes and the Eating Disorder Inventory. The findings indicated that these
      sorority women may have a greater fear of becoming fat, are more dissatisfied
      with their bodies, and are more weight preoccupied and concerned with dieting
      than are college women from previous studies. The findings also suggested that
      body size perceptions were distorted among both underweight and overweight women
      and that thin was the ideal body profile for the majority of the women. Although
      bulimia scores were higher for this population than for those reported in all but
      one of the previous studies, these differences were not significant. More
      research and innovative programs designed to address weight-related attitudes and
      behaviors among this population are called for.

PMID- 9276351
TI  - The impact of a required college health and physical education course on the
      health status of alumni.
AB  - The impact of a required college health and physical education course on selected
      health knowledge, attitudes, and behaviors of alumni was evaluated. The design
      was a cross-sectional study (mail out/mail back survey) using a stratified random
      sample of 2,000 college alumni. The overall response rate was 50%. Results were
      analyzed by college of graduation (college with a required health/physical
      education course versus no required course). Alumni who took the course were more
      likely to know their blood pressure, blood cholesterol, and recommended dietary
      fat intake than the comparison group were. They also reported that the course
      positively influenced their attitudes toward exercise, eating, and smoking They
      were more likely to engage in aerobic exercise and less likely to smoke; and they
      had lower intakes of dietary fat, cholesterol, and sodium. The results suggested
      that a required college course enhanced selected health-related knowledge,
      attitudes, and behaviors of alumni.

PMID- 9276352
TI  - Know your numbers: comparing participants and nonparticipants in a university
      health screening program.
AB  - University faculty and staff members were offered the opportunity to participate
      in a worksite health screening program. Both the participants and the
      nonparticipants responded to a questionnaire concerning their dietary and health
      practices. Participants' values for total serum cholesterol, blood pressure, and
      percentage of body fat were measured. No significant differences between the two
      groups were observed for the parameters of self-reported total serum cholesterol
      or blood pressure, and the participants' self-reported and measured serum
      cholesterol values were not significantly different from those of the
      nonparticipants. However, the measured and self-reported percentages of body fat
      of participants were significantly different from reported percentages of body
      fat of those who did not participate. Further exploration of the motivation of
      participants in health screening programs is called for.

PMID- 9276353
TI  - A marketing technique to increase visibility and use of health center counseling
      services.
AB  - Marketing a university health-center-based counseling service by giving students
      promotional items, such as pens, key tags, refrigerator magnets, and self-stick
      removable note pads bearing telephone numbers and information about counseling
      services is described. This technique, which resulted in 32% more appointments
      scheduled and 25% more students being seen during the 1995/96 academic year than
      had been seen in the 1994/95 academic year, can also be used to increase the use
      of campus health promotion and medical services.

PMID- 9276354
TI  - Influence of an oligodendroglial component on the survival of patients with
      anaplastic astrocytomas: a report of Radiation Therapy Oncology Group 83-02.
AB  - PURPOSE: Seven percent of patients with high grade gliomas enrolled in RTOG 83-02
      had mixed astrocytoma/oligodenroglial elements on central pathology review. It
      has often been assumed that the most aggressive histologic component of a tumor
      determines biologic behavior; however in this trial, the survival of patients who
      had mixed glioblastomas/oligodenrogliomas was significantly longer than that of
      patients with pure glioblastomas (GBM). We therefore evaluated the effect of an
      oligodendroglial component on the survival of patients who had anaplastic
      astrocytomas (AAF) treated in the same trial. METHODS AND MATERIALS: One hundred
      nine patients who had AAF and 24 patients with mixed AAF/oligodendrogliomas
      (AAF/OL) were enrolled in a Phase I/II trial of randomized dose-escalation
      hyperfractioned radiotherapy plus BCNU. AAF/OL patients were older and more
      likely to have had more aggressive surgery than AAF patients. Other pretreatment
      characteristics were balanced between groups, as was assigned treatment. RESULTS:
      The median survival time for AAF was 3.0 years versus 7.3 years for AAF/OL (p =
      0.019). In a multivariate analysis, adjusting for extent of surgical resection
      and age, an oligodendroglial component was an independent prognostic factor for
      survival. CONCLUSION: The results support the concept that AAFs with an
      oligodendroglial component have a better prognosis than pure AAF tumors, similar
      to the effect seen among patients with glioblastoma multiforme tumors. This
      better survival outcome should be taken into consideration in the design and
      stratification of future trials. Additionally, in contrast to patients with GBMs,
      patients who have AAF/OL have the potential for prolonged survival; therefore,
      late sequelae of treatment (both radiation and chemotherapy) must be weighed more
      heavily in the benefits to risks analysis.

PMID- 9276355
TI  - Radiation therapy for histologically confirmed primary central nervous system
      germinoma.
AB  - PURPOSE: To evaluate survival and patterns of recurrence in patients with primary
      central nervous system germinoma treated with radiation therapy. METHODS AND
      MATERIALS: Data regarding 48 patients with histologically confirmed, primary
      central nervous system germinoma were reviewed. All had been operated on at the
      Mayo Clinic between the years 1935 and 1993. Thirty-two patients (67%) were
      treated since 1973. The study group included 39 males and 9 females, with a
      median age at diagnosis of 17 years (range, 6-42 years). Twelve patients (25%)
      were treated with craniospinal axis irradiation, 11 (23%) received whole-brain
      irradiation without spinal axis irradiation, and 24 (50%) underwent partial-brain
      irradiation. Treatment volumes were unknown in one patient. The median dose to
      the primary tumor was 44.00 Gy (range, 7.44-59.40 Gy). The median follow-up was
      5.5 years (range, 4 months to 37 years). RESULTS: Actuarial 5-year and 10-year
      survival for the entire study group of patients was 80%. There was a trend toward
      improved survival in patients treated after 1973 (introduction of computed
      tomography) with 5-year and 10-year survival of 91% vs. 63% in prior years (p =
      0.07). For the group of 31 patients treated since 1973 with known treatment
      volumes, the spinal axis failure rate at 5 years was 49% for patients treated
      with partial brain fields (11 patients) vs. 0% for those having undergone whole
      brain (10 patients) or craniospinal axis (10 patients) irradiation (p = 0.007).
      The rate of brain failure was also significantly higher in patients receiving
      less than whole-brain irradiation; at 5 years, 45% of the patients treated with
      partial-brain fields had intracranial recurrence of disease compared to 6 % of
      patients treated with craniospinal axis or whole-brain irradiation (p = 0.01).
      Among the 32 modern era patients, the rate of brain failure was higher in
      patients who received doses less than 40 Gy (median dose, 48.55 Gy; range, 30.60
      59.40 Gy) to the primary tumor (5-year brain failure rate 52% vs. 11%, p =
      0.002). CONCLUSION: The long-term survival of patients with histologically proven
      CNS germinoma treated with radiation is excellent. Whole-brain or craniospinal
      axis irradiation appears to result in fewer spine and brain failures than does
      partial-brain irradiation. Furthermore, the administration of doses greater than
      40 Gy to the primary tumor is associated with better local control.

PMID- 9276356
TI  - UKCCSG study of accelerated radiotherapy for pediatric brain stem gliomas. United
      Kingdom Childhood Cancer Study Group.
AB  - PURPOSE: Between 1991 and 1994, the United Kingdom Childhood Cancer Study Group
      (UKCCSG) conducted a multicenter study to assess the efficiency and tolerability
      of accelerated radiotherapy in children with a diagnosis of poor-prognosis brain
      stem glioma. METHODS AND MATERIALS: Patients eligible for study were those aged 3
      16 years with tumors arising in the pons, medulla, or midbrain, not previously
      treated with radiotherapy or chemotherapy. Histologic confirmation was not
      mandatory, but computed tomography or magnetic resonance imaging and clinical
      findings had to be typical, and patients were selected with short prediagnosis
      symptom history (<3 months), cranial nerve palsies or long tract signs, and
      intrinsic diffuse lesions on scanning. The treatment dose was 48.6 Gy in 27
      fractions, increased to 50.4 Gy in 28 fractions in January 1992, delivered twice
      daily (except weekends) with an interfraction interval of at least 8 h. Between
      January 1991 and July 1994, 28 available patients were recruited: 15 boys and 13
      girls with ages ranging between 3 and 13 years (median 6). RESULTS: After
      treatment, neurologic improvement sustained for a period of at least 6 weeks
      without steroids was reported in 13 children (46%). On central review of
      postradiotherapy imaging, 50% of children showed evidence of partial response,
      but none exhibited a complete response. A further six patients (22%) had stable
      disease. The median survival time was 37 weeks (8.5 months); 1-year survival was
      32%, and 2-year survival 11%. The pattern of relapse was local in all 26 patients
      who died of their disease; 1 patient had evidence of leptomeningeal seeding.
      Acute radiation morbidity was minimal, with only three patients (11%) exhibiting
      mild toxicity. No evidence of radiation-induced necrosis was found radiologically
      or histologically at postmortem. Ability to withdraw steroids following
      radiotherapy was the single most important prognostic variable in our study.
      CONCLUSION: The results of this study are comparable to previous outcomes of
      studies with conventional and hyperfractionated radiotherapy in poor-prognosis
      brain stem glioma. The fractionation regimen was shown to be tolerable with an
      acceptable morbidity profile. However, further research is required to improve
      the poor prognosis of these unfortunate children.

PMID- 9276357
TI  - Androgen suppression plus radiation versus radiation alone for patients with D1
      (pN+) adenocarcinoma of the prostate (results based on a national prospective
      randomized trial, RTOG 85-31). Radiation Therapy Oncology Group.
AB  - PURPOSE: To evaluate the effect of immediate androgen suppression in conjunction
      with standard external beam irradiation vs. radiation alone on a group of
      pathologically staged lymph node-positive patients with adenocarcinoma of the
      prostate. METHODS AND MATERIALS: A national prospective randomized trial (RTOG 85
      31) of standard external beam irradiation plus immediate androgen suppression vs.
      external beam irradiation alone was initiated in 1985 for patients with locally
      advanced adenocarcinoma of the prostate. One hundred seventy-three of the
      patients in this trial had biopsy-proven pathologically involved lymph nodes.
      Ninety-eight of these patients received radiation plus the immediate androgen
      suppression (LHRH agonist), while 75 received radiation alone with hormonal
      manipulation instituted at the time of relapse. RESULTS: With a median followup
      of 4.9 years, estimated progression-free survival with PSA < 1.5 ng/ml at 5 years
      was 55% for the patients who received radiation plus immediate LHRH agonist vs.
      11% of the patients who received radiation alone with hormonal manipulation at
      relapse (p = 0.0001). Because all of these patients had locally advanced disease
      (i.e., pathologically positive lymph nodes), stage does not explain this
      difference in outcome, and Gleason grade was not statistically different between
      the two groups. Estimated absolute survival at 5 years for the radiation and LHRH
      group was 73 vs. 65% for the radiation alone group who received androgen
      suppression at relapse. Estimated disease-specific survival at 5 years was 82%
      for the radiation and immediate LHRH agonist group and 77% for the radiation
      alone group. CONCLUSION: Patients with adenocarcinoma of the prostate and
      pathologically involved pelvic lymph nodes (pN+ or clinical stage D1) should be
      seriously considered for external beam irradiation plus immediate hormonal
      manipulation over radiation alone with hormonal manipulation at the time of
      relapse.

PMID- 9276358
TI  - Rate of PSA rise predicts metastatic versus local recurrence after definitive
      radiotherapy.
AB  - OBJECTIVE: A rising prostate specific antigen (PSA) following treatment for
      adenocarcinoma of the prostate indicates eventual clinical failure, but the rate
      of rise can be quite different from patient to patient, as can the pattern of
      clinical failure. We sought to determine whether the rate of PSA rise could
      differentiate future local versus metastatic failure. METHODS AND MATERIALS: Two
      thousand six hundred sixty-seven PSA values from 400 patients treated with
      radiotherapy for localized adenocarcinoma of the prostate were analyzed with
      respect to PSA patterns and clinical outcome. Patients had received no hormonal
      therapy or prostate surgery and had > 4 PSA values post-treatment. PSA rate of
      rise, determined by the slope of the natural log, was classified as gradual [<
      0.69 log(ng/ml)/year, or doubling time (DT) > 1 year], moderate [0.69-1.4
      log(ng/ml)/year, or DT 6 months-1 year], or rapid [> 1.4 log(ng/ml)/year, or DT <
      6 months]. RESULTS: Sixty-one percent of patients had non-rising PSA following
      treatment; 25% of patients with rising PSA developed clinical failure, and 93% of
      patients with clinical failure had rising PSA. The rate of rise discerned
      different clinical failure patterns. Local failure occurred in 23% of patients
      with moderate rate of rise versus 7% with gradual rise (p = 0.0001). Metastatic
      disease developed in 46% of those with rapid rise versus 8% with moderate rise (p
      < 0.0001). By multivariate analysis, in addition to rate of rise, PSA nadir and
      rate of decline predicted local failure; those with post-treatment nadir of 1-4
      ng/ml were five times more likely to experience local failure than nadir < 1
      ng/ml (p = 0.0002). Rapid rate of rise was the most significant independent
      predictor of metastatic failure. CONCLUSIONS: The rate of PSA rise following
      definitive radiotherapy can predict clinical failure patterns, with a rapidly
      rising PSA indicating metastatic recurrence and moderately rising PSA local
      recurrence. This information could potentially direct therapy; if the rise
      predicts metastatic failure hormonal therapy could be considered, while
      aggressive salvage therapy may benefit subclinical local recurrence identified by
      a moderate rate of PSA rise.

PMID- 9276359
TI  - Results of conservative surgery and radiation for mammographically detected
      ductal carcinoma in situ (DCIS).
AB  - PURPOSE: The role of conservative surgery and radiation for mammographically
      detected ductal carcinoma in situ (DCIS) is controversial. In particular, there
      is little data for outcome with radiation in a group of patients comparable to
      those treated with local excision and surveillance (mammographic calcifications <
      or = 2.5 cm, negative resection margins, negative postbiopsy mammogram). This
      study reports outcome of conservative surgery and radiation for mammographically
      detected DCIS with an emphasis on results in patients considered candidates for
      excision alone. METHODS AND MATERIALS: From 1983 to 1992, 110 women with
      mammographically detected DCIS (77% calcifications +/- mass) and no prior history
      of breast cancer underwent needle localization and biopsy with (55%) or without a
      reexcision and radiation. Final margins of resection were negative in 62%,
      positive 7%, close 11%, and unknown 20%. The median patient age was 56 years. The
      most common histologic subtype was comedo (54%), followed by cribriform (22%).
      The median pathologic tumor size was 8 mm (range 2 mm to 5 cm). Forty-seven
      percent of patients with calcifications only had a negative postbiopsy mammogram
      prior to radiation. Radiation consisted of treatment to the entire breast (median
      50.00 Gy) and a boost to the primary site (97%) for a median total dose of 60.40
      Gy. RESULTS: With a median follow-up of 5.3 years, three patients developed a
      recurrence in the treated breast. The median interval to recurrence was 8.8 years
      and all were invasive cancers. Two (67%) occurred outside the initial quadrant.
      The 5- and 10-year actuarial rates of recurrence were 1 and 15%. Cause-specific
      survival was 100% at 5 and 10 years. Contralateral breast cancer developed in two
      patients. There were too few failures for statistical significance to be achieved
      with any of the following factors: patient age, family history, race,
      mammographic findings, location primary, pathologic size, histologic subtype,
      reexcision, or final margin status. However, young age, positive or close
      margins, and the presence of a mass without calcifications had a trend for an
      increased risk of recurrence. There were no recurrences in the subset of 16
      patients who would be candidates for surveillance by Lagios' criteria.
      CONCLUSION: For selected patients, conservative surgery and radiation for
      mammographically detected DCIS results in a low risk of recurrence in the treated
      breast and 100% 5- and 10-year cause-specific survival. Improved mammographic and
      pathologic evaluation results in better patient selection and reduces the risk of
      the subsequent appearance of DCIS in the biopsy site. The identification of risk
      factors for an ipsilateral invasive breast recurrence is evolving.

PMID- 9276360
TI  - Early-stage bilateral breast cancer treated with breast-conserving surgery and
      definitive irradiation: the University of Pennsylvania experience.
AB  - PURPOSE: To determine whether patients with early-stage bilateral breast cancer
      can be treated with definitive irradiation following breast-conserving surgery
      with acceptable survival, local control, complications, and cosmesis. METHODS AND
      MATERIALS: During the period 1977-1992, 55 women with Stage 0, I, or II
      concurrent (n = 12) or sequential (n = 43) bilateral breast cancer were treated
      with definitive irradiation following breast-conserving surgery. The records of
      these 55 patients with 110 treated breasts were reviewed for tumor size,
      histology, pathologic axillary lymph node status, first and overall site(s) of
      failure, and adjuvant chemotherapy or hormonal therapy. Curves for survival,
      local control, and regional control were determined. Cosmetic outcome,
      complication rates, and matching technique were analyzed. The median total
      radiation dose delivered was 64 Gy (range 42-72) using tangential whole-breast
      irradiation followed by an electron or iridium implant boost. The tangential
      fields were matched with no overlap in 40 patients (73%); there was overlap on
      skin of up to 4 cm in 14 patients (25%); and the matching technique was unknown
      in 1 patient (2%). The median follow-up for the 12 women with concurrent
      bilateral breast cancer was 4.0 years. The median follow-up for the other 43
      women with sequential cancer was 9.3 and 4.9 years, respectively, after the first
      and second cancers. RESULTS: For the overall group of 55 patients, the 5- and 10
      year overall survival rates were 96% and 94%, respectively, after treatment of
      the first cancer, and 96% and 92%, respectively, after treatment of the second
      cancer. The 5- and 10-year actuarial relapse-free survival rates were 90% and
      75%, respectively, after treatment of the first cancer, and 83% and 72%,
      respectively, after treatment of the second cancer. For the 110 treated breast
      cancers, the 5- and 10-year actuarial local failure rates were 5% and 15%,
      respectively. Complication rates were: 28% breast edema, 8% arm edema, 4%
      pneumonitis, 3% cellulitis, 1% rib fracture, and 1% brachial plexopathy; no
      patient developed matchline fibrosis. For patients with a minimum of 3 years of
      relapse-free follow-up, the rate of excellent or good cosmetic outcome for 104
      treated breasts was 85%. CONCLUSION: Definitive irradiation after breast
      conserving surgery is technically feasible for selected patients with concurrent
      or sequential early-stage bilateral breast cancer. Survival, local control,
      complication rates, and cosmetic outcomes appear comparable to historical reports
      of breast conservation treatment for unilateral disease. Bilateral definitive
      breast irradiation after breast-conservation surgery should be considered an
      acceptable alternative treatment to bilateral mastectomy for selected patients
      with concurrent or sequential early-stage bilateral breast cancer.

PMID- 9276361
TI  - Carcinoma of the intact uterine cervix treated with radiotherapy alone: a French
      cooperative study: update and multivariate analysis of prognostics factors.
AB  - PURPOSE: To determine independent prognostic factors in a group of 1875 patients
      with invasive carcinoma of the intact uterine cervix treated with radiotherapy
      alone in a French cooperative study from 1970 to 1993. MATERIALS AND METHODS:
      Patients were staged according to the UICC-FIGO and MDAH substaging. The
      distribution per FIGO stage was Ia-Ib: 25.5%; IIa: 12%; IIb: 29%; IIIa: 5%; IIIb:
      25%, and IV: 3.5%. Ninety-two percent had squamous cell carcinoma. The maximum
      diameter of the clinically detectable cervical disease was less than 3 cm in
      24.5% of Stages I-II and in 10% of Stages III-IV, more than 5 cm in 13.5% of
      Stages I-II, and in 16% of Stages III-IV. Nodal involvement was shown on
      lymphangiogram in 16% of Stages I-II and in 32.5% of Stages III-IV. RESULTS: 1)
      Univariate analysis of Stages I and II: stage, cervical disease diameter, and
      nodal involvement are significant prognostic factors. Five-year specific survival
      rate (5ySS) is 83.5% in Stage Ib, 81% in IIa and 71% in IIb. Five-year disease
      free survival rate (5yDFS) is 86% in tumors less of 3 cm, 76% in tumors of 3 to 5
      cm, and 61.5% in tumor larger than 5 cm. Lymphangiogram strongly influences the 5
      year pelvic disease-free survival rate (5yPDFS): respectively, 90% in nonpositive
      lymphangiogram vs. 65% when positive. A significant drop in specific and disease
      free survival is observed (10 and 14%, respectively (p = 0.04) when comparing
      adenocarcinoma and squamous cell carcinoma. Age is a significant prognostic
      factor for specific survival because patients aged less than 30 years old have
      91% vs. about 75% for patients over 30 years (p = 0.03). 2) Univariate analysis
      of Stages III-IV: Stage and positive lymphangiogram are predictive factors for
      relapse and death. The MDAH substaging is more reliable to predict the
      probability of pelvic disease-free survival in Stage III. At 5 years, the FIGO
      Stages IIIa and IIIb have a rather similar PDFS (65% vs. 59%). Conversely, the
      difference of survival rates between MDAH Stage IIIA and Stage IIIB is more
      demonstrative (69% vs. 47.5%). 3) Multivariate analysis (Cox P. H. R. model).
      Nodal involvement and stage remain significant for all three models in all stages
      (p < 0.0001). Age above 70 years influences specific survival for Stage I-II (p =
      0.01). Tumors larger than 5 cm and adenocarcinoma also appear to be independent
      prognostic factors for specific and disease-free survival in Stage I-II (p = 0.05
      and p = 0.005, respectively). CONCLUSIONS: The relevance of tumor size (less or
      greater than 4 cm) is now recognized in the 1995 revised FIGO staging in Stage Ib
      but unfortunately not in other stages. Tumor size per stage and nodal status
      should be systematically recorded to allow a better prediction of failure rates
      and to compare literature reports.

PMID- 9276362
TI  - Role of mitomycin C in the development of late bowel toxicity following
      chemoradiation for locally advanced carcinoma of the cervix.
AB  - PURPOSE: To determine if the inclusion of mitomycin C (MMC) in chemoradiation
      protocols for locally advanced cervical cancer (LACC) significantly enhances the
      development of serious (Grade 3) late bowel toxicity (SLBT). METHODS AND
      MATERIALS: The incidence of SLBT in 154 patients with LACC entered in six
      consecutive chemoradiotherapy protocols between February 1982 and June 1987 was
      determined. Fifty-four patients who were treated with MMC, 5-fluorouracil (5-FU),
      and radiation were compared to 100 patients who received similar treatment
      without MMC. Univariate and multivariate analyses assessed the effect of the
      following parameters on the development of SLBT: (a) external beam dose, (b)
      rectal and rectosigmoid dose, (c) paraaortic radiation, (d) intracavitary dose
      and dose rate, (e) volume of tissue irradiated to a total dose of 60 Gy, (f)
      International Federation of Gynecology and Obstetrics stage, (g) age, (h) number
      of courses of 5-FU, (i) previous abdominopelvic surgery, (j) split versus
      continuous radiation, and (k) administration of MMC. RESULTS: The overall
      incidence of SLBT was 15.6%: 14 of 54 (26%) versus 10 of 100 (10%) for patients
      who did or did not receive MMC, respectively (p = 0.009). Multivariate analysis
      revealed the administration of MMC as the only factor predictive for the
      development of SLBT (p = 0.012, odds ratio = 3.15; 95% confidence interval 1.3
      7.7). A significant reduction in SLBT was observed with the elimination of MMC
      from the chemoradiation protocols despite dose escalation of both radiation and 5
      FU. No increase in overall survival was observed in patients receiving MMC, 5-FU,
      and radiation compared with 5-FU and radiation alone. CONCLUSION: The inclusion
      of MMC in these chemoradiation protocols for LACC is associated with significant
      enhancement in serious late bowel toxicity.

PMID- 9276363
TI  - The prediction of late rectal complications in patients treated with high dose
      rate brachytherapy for carcinoma of the cervix.
AB  - PURPOSE: The aim of this work is to investigate an unusually high rate of late
      rectal complications in a group of 43 patients treated with concomitant
      irradiation and chemotherapy for carcinoma of the cervix between December 1988
      and April 1991, with a view to identifying predictive factors. METHODS AND
      MATERIALS: The biologically effective dose received by each patient to the rectal
      reference point defined by the International Commission of Radiation Units and
      Measurements, Report 38, were calculated. Radiotherapy consisted of 46 Gy
      external beam irradiation plus three high dose-rate intracavitary treatments of
      10 Gy each prescribed to point A. Cisplatin 30 mg/m2 was given weekly throughout
      the duration of the irradiation. The results have been compared to data from 119
      patients treated with irradiation alone to assess the confounding effect of the
      cisplatin. RESULTS: The relationship between the biologically effective dose
      delivered to the rectal reference point and the development of late complications
      shows a strong dose-response with a threshold for complications occurring at
      approximately 125 Gy3 corresponding to a brachytherapy dose of approximately 8 Gy
      per fraction. This value is approximately the same biologically effective dose
      threshold as that found for external beam irradiation in the head and neck
      region. The data from the group of patients treated without cisplatin is
      comparable to the data from the first group of patients in the lower dose ranges;
      the higher doses were not used and thus are not available for comparison.
      CONCLUSION: Using the linear quadratic model applied to our clinical results, we
      have established a threshold for late rectal complications for patients treated
      with external beam irradiation and high dose-rate brachytherapy for carcinoma of
      the cervix. This threshold is consistent with similar data for external beam
      irradiation in the head and neck region.

PMID- 9276364
TI  - Long-term regional control after radiation therapy and neck dissection for base
      of tongue carcinoma.
AB  - PURPOSE: Minimal literature exists with 10-year data on neck control in advanced
      head and neck cancer. The purpose of this study is to determine long-term
      regional control for base of tongue carcinoma patients treated with primary
      radiation therapy plus neck dissection. METHODS AND MATERIALS: Between 1981-1996,
      primary radiation therapy was used to treat 68 patients with squamous cell
      carcinoma of the base of tongue. Neck dissection was added for those who
      presented with palpable lymph node metastases. The T-stage distribution was T1,
      17; T2, 32; T3, 17; and T4, 2. The N-stage distribution was N0, 10; N1, 24; N2a,
      6; N2b, 11, N2c, 8; N3, 7; and Nx, 2. Ages ranged from 35 to 77 (median 55 years)
      among the 59 males and nine females. Therapy generally consisted of initial
      external beam irradiation to the primary site (54 Gy) and neck (50 Gy).
      Clinically positive necks were boosted to 60 Gy with external beam irradiation.
      Three weeks later, the base of tongue was boosted with an Ir-192 interstitial
      implant (20-30 Gy). A neck dissection was done at the same anesthesia for those
      who presented with clinically positive necks, even if a complete clinical neck
      response was achieved with external beam irradiation. Neoadjuvant cisplatin-based
      chemotherapy was administered to nine patients who would have required a total
      laryngectomy if their primary tumors had been surgically managed. The median
      follow-up was 36 months with a range from 1 to 151 months. Eleven patients were
      followed for over 8 years. No patients were lost to follow-up. RESULTS: Actuarial
      5- and 10-year neck control was 96% overall, 86% after radiation alone, and 100%
      after radiation plus neck dissection. Pathologically negative neck specimens were
      observed in 70% of necks dissected after external beam irradiation. The remaining
      30% of dissected necks were pathologically positive. These specimens contained
      multiple positive nodes in 83% despite a 56% overall complete clinical neck
      response rate to irradiation. Regional failure occurred in only two patients,
      neither of whom underwent adjuvant neck dissection. Symptomatic neck fibrosis
      (RTOG grade 3) was not observed. Actuarial 5- and 10-year local control was 88%
      and 88%, disease-free survival was 80% and 67%, and overall survival was 86% and
      52%. CONCLUSION: For base of tongue cancer, most patients can obtain long-term
      regional control with no severe complications after definitive radiation therapy,
      plus neck dissection for those who present with lymphadenopathy. Complete
      clinical regression of palpable neck metastases after irradiation poorly
      correlates with pathologic outcome. Our current policy is to include neck
      dissection at the time of implantation for patients who present with palpable
      neck metastases. We realize that this therapeutic approach may overtreat some
      patients, but we are reluctant to change our policy in light of these excellent
      outcomes.

PMID- 9276365
TI  - Definitive radiotherapy for early glottic carcinoma: prognostic factors and
      implications for treatment.
AB  - PURPOSE: Treatment and disease-related factors were analyzed for their influence
      on the outcome of patients treated definitively with irradiation (RT) for early
      glottic carcinoma. METHODS AND MATERIALS: One hundred two patients with stage T1
      or T2 glottic carcinomas were treated definitively with RT from December 1983
      through September 1993. Median follow-up time was 63 months. Factors analyzed for
      each patient included age, sex, stage, anterior commissure involvement, surgical
      alternative, histologic differentiation, field size, total dose, fraction size,
      and total treatment time. Survival analysis methods were employed to assess the
      effects of these factors on local control and complication rates. RESULTS: The 5
      year local control rates by stage were as follows: T1a, 92%; T1b, 80%; T2a, 94%;
      and T2b, 23%. By univariate analysis, factors found to have a significant impact
      on local control were stage, surgical alternative, fraction size, anterior
      commissure involvement, and overall treatment time. By multivariate analysis,
      stage, field size, and fraction size were the only significant factors that
      independently influenced local control. CONCLUSION: The inferior control rate for
      stage T2b lesions has implications for treatment. Our study supports the
      conclusion of reports in the literature showing that low fraction size negatively
      influences outcome in patients with early glottic cancer.

PMID- 9276366
TI  - Prognostic value of hemoglobin concentration in radiotherapy for cancer of
      supraglottic larynx.
AB  - PURPOSE: The aim of this work is the estimation of correlations between
      hemoglobin concentration either before or after radiotherapy and local tumor
      control probability for laryngeal cancer. METHODS AND MATERIALS: Retrospective
      analysis of 847 cases of laryngeal supraglottic squamous cell carcinoma treated
      with radiation alone was performed using maximum likelihood estimations, and step
      wise logistic regression. All patients were in good initial performance status
      (Karnofsky index >70). The minimum follow-up time was 3 years. RESULTS: Logistic
      regression showed that the hemoglobin concentration after radiotherapy is an
      important prognostic factor. There was a very strong correlation between
      hemoglobin concentration and tumor local control probability. Hemoglobin
      concentration at the beginning of radiotherapy does not correlate with treatment
      outcome, but any decrease of hemoglobin during therapy is a strong prognostic
      factor for treatment failure. CONCLUSIONS: Although regression models with many
      variables may be instable, the present results suggest that hemoglobin
      concentration after treatment is at least as important as overall treatment time.
      It was not possible to find out whether the low concentration of hemoglobin is an
      independent cause of low TCP or whether it reflects other mechanisms that may
      influence both hemoglobin level and the TCP.

PMID- 9276368
TI  - Radiotherapy treatment for isolated loco-regional recurrence of rectosigmoid
      cancer following definitive surgery: Peter MacCallum Cancer Institute experience,
      1981-1990.
AB  - PURPOSE: To assess the success of external beam radiation treatment in the
      management of loco-regional recurrence of rectosigmoid cancer. METHODS AND
      MATERIALS: A retrospective analysis of 135 patients with locally recurrent
      rectosigmoid cancer presenting to Peter MacCallum Cancer Institute between
      January 1981 and December 1990 was undertaken. Patients were treated with three
      different dose ranges of radiotherapy: 50-60 Gy ("Radical" group), 45 Gy ("High
      dose palliative" group), and <45 Gy ("Low-dose palliative" group). Symptomatic
      response rates and overall survival for each group were determined. RESULTS:
      Symptomatic response rates of 85, 81, and 56% were achieved in the radical, high
      dose palliative, and low-dose palliative groups, respectively. Estimated median
      survival times were 17.9, 14.8, and 9.1 months for the radical, high-dose
      palliative, and low-dose palliative groups, respectively.

PMID- 9276367
TI  - Accelerated fractionation in esophageal cancers: a multivariate analysis on 88
      patients.
AB  - PURPOSE: Accelerated fractionation was used to shorten overall treatment time to
      increase locoregional control and cause-specific survival. METHODS AND MATERIALS:
      Eighty-eight patients with cancer of the esophagus ineligible for surgery were
      entered in the study between 1986 and 1993. Neoadjuvant chemotherapy was given to
      64% of patients. Accelerated radiotherapy using the concomitant boost technique
      delivered a median dose of 65 Gy in a median overall treatment time of 32 days.
      RESULTS: The 3-year actuarial local control rate in patients with T1, T2, and T3
      tumors was 71%, 42%, and 33%, respectively. The 3-year cause-specific survival
      rates were 40%, 22%, and 6%, respectively. Sixteen percent of patients
      experienced Grade 3 esophagitis. Late toxicity included esophageal stenosis and
      pulmonary fibrosis in 8% and 9% of the patients, respectively. Multivariate
      analysis demonstrated that T stage and overall treatment time were prognostic
      factors for cause-specific survival. T stage and neoadjuvant chemotherapy were
      independent prognostic factors for locoregional control. CONCLUSION: These
      findings suggest that accelerated fractionation given in an overall treatment
      time of <35 days might be beneficial for early-stage cancer of the esophagus.
      Neoadjuvant chemotherapy is not recommended, as it was a significant adverse
      prognostic factor in the multivariate analysis for local control. Accelerated
      fractionation can be carried out with moderate acute and late toxicity.

PMID- 9276369
TI  - Total skin electron beam therapy followed by adjuvant psoralen/ultraviolet-A
      light in the management of patients with T1 and T2 cutaneous T-cell lymphoma
      (mycosis fungoides).
AB  - PURPOSE: Patients with mycosis fungoides [cutaneous T-cell lymphoma (CTCL)] may
      benefit from adjuvant therapy after completing total skin electron beam therapy
      (TSEBT). We report the results for T1/T2 CTCL patients treated with adjuvant oral
      psoralen plus ultraviolet light (PUVA) with respect to overall survival (OS),
      disease-free survival (DFS), salvage of recurrence, and toxicity. METHODS AND
      MATERIALS: Between 1974 and 1993, TSEBT was administered to a total of 213
      patients with CTCL. Records were reviewed retrospectively, and a total of 114
      patients were identified as having T1 or T2 disease. Radiotherapy was provided
      via a 6-MeV linac to a total of 36 Gy, 1 Gy/day, 4 days/week, for 9 weeks.
      Beginning in 1988, patients were offered adjuvant PUVA within 2 months of
      completing TSEBT. This was started at 0.5-2 J/m2, 1-2 treatments/week, with a
      taper over 3-6 months. Therapy then continued once per month. There were 39 T1
      and 75 T2 patients. Six T1 (15%) and eight T2 (11%) patients were treated with
      adjuvant PUVA. A further 49% of the 114 patients received adjuvant systemic
      therapy, 3% received spot external beam, 4% received adjuvant ECP, 2% received
      topical nitrogen mustard, 22% received a combination of therapies exclusive of
      PUVA, and 9% received no adjuvant therapy. Patients were balanced in all
      subgroups based on pre-TSEBT therapy. The median age of the cohort was 58 (range
      20-88), with a median follow-up time of 62 months (range 3-179). RESULTS: Within
      1 month after completing of TSEBT, 97% of T1, and 87% of T2 patients had achieved
      a complete remission. Stratified by adjuvant therapy, none of six T1 and one of
      eight T2 patients who received adjuvant PUVA failed within the first 3 years
      after completion of TSEBT. A total of 43% of the T1 and T2 patients receiving
      other or no adjuvant treatment failed within the same time course. The 5-year OS
      for the entire cohort was 85%. Those who received PUVA had a 5-year OS of 100%
      versus a 5-year OS for the non-PUVA group of 82% (p < 0.10). The 5-year DFS for
      the entire cohort was 53%. Those who received PUVA had a 5-year DFS of 85% versus
      a 5-year DFS for the non-PUVA group of 50% (p < 0.02). By T stage, those with T1
      receiving PUVA exhibited no relapses, whereas those with T1 not treated with PUVA
      had a crude relapse rate of 36%. Median DFS was not reached at 103 months for the
      T1 adjuvant PUVA patients versus 66 months for the non-PUVA patients (p < 0.01).
      For those with T2, crude relapse rates were 25% and 55%, respectively, with DFS
      of 60 (median DFS not reached) and 20 months (p < 0.03). The 5-year DFS for
      patients salvaged with PUVA was 50%. Toxicity of adjuvant and salvage PUVA
      therapy was acceptable, with only two patients requiring a reduction in PUVA
      dosage. CONCLUSION: PUVA can maintain remissions in patients with CTCL after
      TSEBT. There is a significant benefit in DFS but no statistically significant
      improvement in OS. Prospective, randomized data are needed to confirm these
      results. PUVA is also effective as a salvage therapy after TSEBT in early-stage
      patients with recurrence, with acceptable toxicity.

PMID- 9276370
TI  - Short-course radiotherapy (8 Gy x 2) in metastatic spinal cord compression: an
      effective and feasible treatment.
AB  - PURPOSE: To evaluate the clinical outcome and toxicity of a short-course regimen
      of radiotherapy (RT) in selected metastatic spinal cord compression (MSCC)
      patients. METHODS AND MATERIALS: Between 1993 and 1995, 53 consecutive patients
      with MSCC from low radio-responsive primary tumors (non small cell lung, kidney,
      head and neck and gastrointestinal carcinomas, melanoma and sarcomas), or more
      radio-responsive ones (breast and prostate carcinomas, myeloma and lymphomas)
      with paresis, plegia, low performance status (PS ECOG > or = 2), and/or short
      life expectation, underwent short-course RT; a single fraction of 8 Gy repeated
      after 1 week in responders or stable patients, for a total dose of 16 Gy. Of 49
      (92%) evaluable cases, 4 (8%) underwent surgery plus RT and the other 45 RT
      alone. Medium doses of parenteral dexamethasone (8 mg x 2/d) were given in all
      cases and precautional anti-emetics to those treated with fields covering the
      upper abdomen (20 of 49 cases). Median follow up was 25 months (range, 6-34).
      Response was assessed according to back pain, and motor and bladder capacity
      before and after RT. RESULTS: Pain relief was achieved in 67% of patients and
      motor function response rate reached 63%. Early diagnosis and therapy were very
      important in predicting response to RT; all but two (91%) pretreatment walking
      patients and all but one (98%) with good bladder function preserved these
      capacities. On the contrary, when diagnosis was late, only 38% of nonambulatory
      patients and 44% of those with bladder retention improved. Median survival was 5
      months, with a 30% probability of survival for 1 year. Length of survival was
      significantly longer for patients able to walk before and/or after RT. Good
      agreement between survival and duration of response was found with no evidence of
      relapse in the irradiated spine. Sickness appeared only in a few cases. Slight
      esophagitis was more frequent: dysphagia for solid foods in one-third of patients
      irradiated on the thoracic spine. Late toxicity was never recorded. CONCLUSION:
      The short-course RT adopted gave a clinical outcome comparable with that
      resulting from more protracted regimens with only slight side effects. The use of
      a few large treatment fractions could be explored considering the associated
      advantages for patients and radiotherapy centers often overloaded by long patient
      waiting lists.

PMID- 9276371
TI  - Spatial heterogeneity of the volume effect for radiation pneumonitis in mouse
      lung.
AB  - PURPOSE: In a previous study to determine the effect of partial volume
      irradiation on damage and morbidity from pneumonitis in mouse lung, a critical
      determinant of the volume effect was the spatial location of the irradiated
      subvolume within the lung. The goals of the present study were to (a) define the
      dose-volume effect curves for radiation pneumonitis in mouse lung, (b) define the
      threshold volume, and (c) further investigate the spatial heterogeneity of the
      radiosensitivity of mouse lung. METHODS AND MATERIALS: Eight fractional volumes
      ranging from 94% to 17% of the lungs of C3Hf/Kam mice were irradiated with single
      doses ranging from 12 to 22 Gy, depending on the volume irradiated. The
      fractional volumes irradiated were determined from computed tomographic scans of
      mouse lung. To determine the effect of location of irradiated subvolume,
      equivalent volumes in the base and the apex were irradiated by shielding the
      prescribed adjacent volume in the apex or base respectively. Dose-response curves
      of breathing rate at 22 weeks and lethality at 28 weeks were constructed for each
      subvolume irradiated in the apex or base and fitted by logit analysis, and ED50s
      and LD50s with 95% confidence limits obtained, respectively. Lungs from dead mice
      or mice sacrificed when moribund were examined for histologic signs of
      pneumonitis. RESULTS: Irradiation of any of the eight subvolumes in the base
      yielded a consistently lower isoeffect dose for both assays of radiation
      pneumonitis than if the same irradiated subvolume was located in the apex. Plots
      of isoeffect dose for breathing rate as a function of subvolume irradiated in the
      base or apex showed that these curves were not linear but exhibited a plateau
      between irradiated volumes of 70% and 80% in both the apex and base. A similar
      curve was obtained for lethality and volume irradiated in the base. A threshold
      volume, i.e., irradiation of that volume that should produce no changes in
      breathing rate or mortality, was dependent on the location of the irradiated
      subvolume. CONCLUSION: The response of mouse lung to partial volume irradiation
      is heterogeneous and is critically dependent on the specific location of the
      irradiated subvolume in the lung, i.e., a given subvolume in the base is
      consistently more sensitive than the same subvolume in the apex using either
      breathing rate or lethality as assays of radiation pneumonitis. We suggest that
      this heterogeneity is due to the anatomy of the tracheobronchial tree, i.e., to
      the distribution of non-gas exchange-conducting airways in the irradiated volume.
      These data have implications for the modeling of dose-volume effects in the lung
      and the prediction of normal tissue complication probabilities for radiation
      pneumonitis in humans.

PMID- 9276372
TI  - Estimation of the spatial distribution of target cells for radiation pneumonitis
      in mouse lung.
AB  - PURPOSE: Recent studies of Liao et al. and Travis et al. have demonstrated that
      irradiation of cross-sectional partial volumes contiguous to the base of mouse
      lung produces a higher incidence of pneumonitis than irradiation of equally sized
      subvolumes contiguous to the apex. One interpretation of this finding is that the
      critical target cells for pneumonitis are not distributed uniformly throughout
      the lung. The purpose of the present study was to test this interpretation by
      obtaining an estimate of the spatial distribution of the critical target cells
      for pneumonitis in mouse lung, based on the partial-volume data. METHODS AND
      MATERIALS: A mathematical model was derived describing the probability of
      radiation pneumonitis as a function of dose, volume of lung irradiated, and
      location in the lung of the irradiated subvolume. The model includes a
      nonparametric description of the spatial target-cell distribution in lung, to be
      estimated from data. The model was fitted to the lethality data of Liao et al.
      and Travis et al. to obtain estimates of the proportion of target cells contained
      in each of various subvolumes of the lung. RESULTS: The results indicate that the
      critical target cells in mouse lung are concentrated in the base and, to a
      somewhat lesser extent, in the apex of the lung, with fewer cells in the middle
      region. The estimated spatial distribution of target cells in mouse lung agrees
      well with the distribution of alveoli, whose concentration in the midlung is
      limited by the presence of the major conducting airways. CONCLUSION:
      Heterogeneity in the spatial distribution of critical target cells in normal
      tissue implies that the complication probability (NTCP) depends on the location
      in the organ of the irradiated subvolume, as well as on radiation dose and
      subvolume size. Calculations using an NTCP model for mouse lung indicate that
      irradiation of equal subvolumes of lung with the same dose can lead to
      complication probabilities covering the full range from 0 to 100%, depending only
      on the location in the lung of the irradiated subvolume.

PMID- 9276373
TI  - Androgen deprivation and radiation therapy: sequencing studies using the Shionogi
      in vivo tumor system.
AB  - PURPOSE: To test the relative effect of neoadjuvant and adjuvant androgen
      deprivation on the radiation response of an androgen dependent tumor. METHODS AND
      MATERIALS: The transplantable, androgen dependent, Shionogi adenocarcinoma was
      grown as allografts in the hind limbs of NCr/Sed (nu/nu) athymic nude mice.
      Bilateral orchiectomy was the chosen form of androgen deprivation. Groups of
      tumors were irradiated to graded tumor doses and then studied for durable tumor
      control. The radiation response was expressed as the radiation dose required to
      control 50% of the tumors (TCD50). The sequence of radiation and orchiectomy was
      studied. RESULTS: When radiation was combined with orchiectomy the Shionogi tumor
      was significantly more likely to be controlled than when radiation was used
      alone. Orchiectomy 12 days prior to radiation (neoadjuvant therapy) produced a
      significantly greater decline in the TCD50 than when orchiectomy was used 1 day
      or 12 days after radiation (adjuvant therapy). If, before radiation, tumors were
      allowed to regrow after orchiectomy to their original size in an androgen
      independent fashion then the advantage was largely lost. Those tumors responding
      well to neoadjuvant orchiectomy (>50% volume decrease) were significantly more
      likely to be eradicated by radiation than those with a lesser response.
      CONCLUSION: When using combinations of androgen deprivation and radiation in the
      treatment of the Shionogi tumor, sequence and timing of the therapies are crucial
      to maximize the effect.

PMID- 9276374
TI  - Supraadditive apoptotic response of R3327-G rat prostate tumors to androgen
      ablation and radiation.
AB  - PURPOSE: Androgen ablation is often combined with radiation in the treatment of
      patients with prostate cancer, yet, the optimal sequencing and the mechanisms
      governing the interaction are not understood. The objectives were to determine if
      cell killing via apoptosis is enhanced when the combined treatment is
      administered and to define the relationship of changes in this form of cell
      killing to tumor volume growth delay. MATERIALS AND METHODS: Dunning R3327-G rat
      prostate tumors, grown in the flanks of Copenhagen rats, were used at a volume of
      approximately 1 cc. Androgen ablation was initiated by castration, and androgen
      restoration was achieved with 0.5 cm silastic tube implants containing
      testosterone. 60Co was used for irradiation. The terminal deoxynucleotidyl
      transferase (TUNEL) histochemical assay was used to quantify apoptosis. RESULTS:
      Tumors from intact and castrate unirradiated control rats had average apoptotic
      indices (percent of apoptotic cells) of 0.4 and 1.0%, respectively. The apoptotic
      index varied only slightly over time (3 h to 28 days) after castration (range
      0.75-1.43%). Irradiation of intact rats to 7 Gy resulted in a peak apoptotic
      response at 6 h of 2.3%. A supraadditive apoptotic response was seen when
      castration was initiated 3 days prior to 7 Gy radiation, with peak levels of
      about 10.1%. When the radiation was administered at increasing times beyond 3
      days after castration, the apoptotic response gradually diminished and was back
      to levels seen in intact rats by 28 days after castration. Tumor volume growth
      delay studies were consistent with, but not conclusive proof of, a supraadditive
      effect when the combination was used. DISCUSSION: A supraadditive apoptotic
      response was seen when androgen ablation and radiation were used to treat
      androgen sensitive R3327-G rat prostate tumors. This supraadditive effect was
      dependent on the timing of the two treatments. Further studies are required to
      more fully define the optimal timing and administration of androgen ablation and
      radiation.

PMID- 9276375
TI  - Radiation-induced apoptosis in different pH environments in vitro.
AB  - PURPOSE: The effect of environmental pH on the radiation-induced apoptosis in
      tumor cells in vitro was investigated. METHODS AND MATERIALS: Mammary
      adenocarcinoma cells of A/J mice (SCK cells) were irradiated with gamma-rays
      using a 137Cs irradiator and incubated in media of different pHs. After
      incubation at 37 degrees C for 24-120 h the extent of apoptosis was determined
      using agarose gel electrophoresis, TdT-mediated dUTP-biotin nick end labeling
      (TUNEL) staining, flow cytometry, and release of 3H from 3H-thymidine labeled
      cells. The clonogenicity of the cells irradiated in different pH medium was
      determined, and the progression of cells through the cell cycle after irradiation
      in different pHs was also determined with flow cytometry. RESULTS: Irradiation
      with 2-12 Gy of gamma-rays induced apoptosis in SCK cells in pH 7.5 medium within
      48 h as judged from the results of four different assays mentioned. Radiation
      induced apoptosis declined as the medium pH was lowered from 7.5 to 6.4.
      Specifically, the radiation-induced degradation of DNA including the early DNA
      breaks, as determined with the TUNEL method, progressively declined as the medium
      pH was lowered so that little DNA fragmentation occurred 48 h after irradiation
      with 12 Gy in pH 6.6 medium. When the cells were irradiated and incubated for 48
      h in pH 6.6 medium and the medium was replaced with pH 7.5 medium, DNA
      fragmentation promptly occurred. DNA fragmentation also occurred even in pH 6.6
      medium when the cells were irradiated and maintained in pH 7.5 medium for 8 h or
      longer post-irradiation before incubation in pH 6.6 medium. The radiation-induced
      G2 arrest in pH 6.6 medium lasted markedly longer than that in pH 7.5 medium.
      CONCLUSION: Radiation-induced apoptosis in SCK cells in vitro is reversibly
      suppressed in an acidic environment. Taking the results of four different assays
      together, it was concluded that early step(s) in the apoptotic pathway, probably
      the DNA break or upstream of DNA break, is reversibly halted by an acidic
      environment in irradiated cells. Radiation-induced G2 arrest is prolonged in an
      acidic environment indicating that the suppression of radiation-induced apoptosis
      and prolongation of radiation-induced G2 arrest in an acidic environment are
      related.

PMID- 9276376
TI  - Transfection of p53-knockout mouse fibroblasts with wild-type p53 increases the
      thermosensitivity and stimulates apoptosis induced by heat stress.
AB  - PURPOSE: The relationship between p53 functions and cellular thermosensitivity
      was evaluated using murine fibroblasts transfected with either wild-type p53 or
      mutated p53, or those with a null p53 genotype. METHODS AND MATERIALS: Cellular
      thermosensitivity was determined using the clonogenic assay. Cell cycle
      distribution was assayed by determining DNA content using flow cytometry.
      Apoptosis was analyzed by detection of both apoptotic bodies and DNA
      fragmentation. RESULTS: Stable transfectant with either wild-type p53 or mutated
      p53 was established. The transfectants with wild-type p53 were more
      thermosensitive than either those with a null p53 or with mutated p53. Although
      heat-induced G1 cell cycle arrest was substantially observed in all
      transfectants, wild-type p53 enhanced and prolonged the G1 arrest; furthermore,
      wild-type p53 stimulated the induction of apoptosis by heat stress, whereas
      mutated p53 delayed it extremely. CONCLUSION: The p53 gene is a factor for
      determining cellular thermosensitivity and wild-type p53 contributes to
      thermosensitization resulting in enhancement of heat-induced apoptosis.

PMID- 9276378
TI  - Dose-volume histograms for bladder and rectum.
AB  - PURPOSE: A careful examination of the foundation upon which the concept of the
      Dose-Volume Histogram (DVH) is built, and the implications of this set of
      parameters on the clinical application and interpretation of the DVH concept has
      not been conducted since the introduction of DVHs as a tool for the quantitative
      evaluation of treatment plans. The purpose of the work presented herein is to
      illustrate problems with current methods of implementing and interpreting DVHs
      when applied to hollow anatomic structures such as the bladder and rectum.
      METHODS AND MATERIALS: A typical treatment plan for external beam irradiation of
      a patient with prostate cancer was chosen to provide a data set from which DVH
      curves for both the bladder and rectum were calculated. The two organs share the
      property of being shells with contents that are of no clinical importance. DVHs
      for both organs were computed using a solid model and using a shell model.
      Typical treatment plans for prostate cancer were used to generate DVH curves for
      both models. The Normal Tissue Complication Probability (NTCP) for these organs
      is discussed in this context. RESULTS: For an eight-field conformal treatment
      plan of the prostate, a bladder DVH curve generated using the shell model is
      higher than the corresponding curve generated using the solid model. The shell
      model also has a higher NTCP. A six-field conformal treatment plan also results
      in a higher DVH curve for the shell model. A treatment plan consisting of
      bilateral 120-degree arcs, results in a higher DVH curve for the shell model, as
      well as a higher NTCP. CONCLUSION: The DVH concept currently used in evaluation
      of treatment plans is problematic because current practices of defining exactly
      what constitutes "bladder" and "rectum." Commonly used methods of tracing the
      bladder and rectum imply use of a solid structure model for DVHs. In reality,
      these organs are shells and the critical structure associated with NTCP is
      obviously and indisputably the shell, as opposed to its contents. Treatment
      planning algorithms for DVH computation should thus be modified to utilize the
      shell model for these organs.

PMID- 9276377
TI  - Three-dimensional visualization and measurement of conformal dose distributions
      using magnetic resonance imaging of BANG polymer gel dosimeters.
AB  - PURPOSE/OBJECTIVE: The measurement of complex dose distributions (those created
      by irradiation through multiple beams, multiple sources, or multiple source dwell
      positions) requires a dosimeter that can integrate the dose during a complete
      treatment. Integrating dosimeter devices generally are capable of measuring only
      dose at a point (ion chamber, diode, TLD) or in a plane (film). With increasing
      use of conformal dose distributions requiring shaped, noncoplanar beams, there
      will be an increased requirement for a dosimeter that can record and display a 3D
      dose distribution. The use of a 3D dosimeter will be required to confirm the
      accuracy of treatment plans produced by the current generation of 3D treatment
      planning computers. METHODS AND MATERIALS: The use of a Fricke-infused gel and
      magnetic resonance imaging (MRI) to demonstrate the localization of stereotactic
      beams has been demonstrated (11). The recently developed BANG polymer gel
      dosimetry system (MGS Research, Inc., Guilford, CT), based on radiation-induced
      chain polymerization of acrylic monomers dispersed in a tissue-equivalent gel,
      surpasses the Fricke-gel method by providing accurate, quantitative dose
      distribution data that do not deteriorate with time (6, 9). The improved BANG2
      formulation contains 3% N,N'-methylene-bisacrylamide, 3% acrylic acid, 1% sodium
      hydroxide, 5% gelatin, and 88% water, where all percentages are by weight. The
      gel was poured into volumetric flasks, of dimensions comparable to a human head.
      The gels were irradiated with complex beam arrangements, similar to those used
      for conformal radiation therapy. Images of the gels were acquired using a Siemens
      1.5T imager and a Hahn spin-echo pulse sequence (90 degrees-tau-180 degrees-tau
      acquire, for different values of tau). The images were transferred via network to
      a Macintosh computer for which a data analysis and display program was written.
      The program calculates R2 maps on the basis of multiple TE images, using a
      monoexponential nonlinear least-squares fit based on the Levenberg-Marquardt
      algorithm. The program also creates a dose-to-R2 calibration function by fitting
      a polynomial to a set of dose and R2 data points, obtained from gels irradiated
      in test tubes to known doses. This function can then be applied to any other R2
      map, so that a dose map can be computed and displayed. RESULTS: Through exposure
      to known doses of radiation, the gel has been shown to respond linearly with dose
      in the range of 0 to 10 Gy, and its response is independent of the beam energy or
      modality. Dose distributions have been imaged in orthogonal planes, and can be
      displayed in a convenient form for comparison with isodose plans. The response of
      the gel is stable; the gel can be irradiated at any time after its manufacture,
      and imaging can be conducted any time following a brief interval after
      irradiation. CONCLUSION: The polymer gel dosimeter has been shown to be a
      valuable device for displaying three-dimensional dose distributions. The imaged
      dose distribution can be compared easily with calculated dose distributions, to
      validate a treatment planning system. In the future, gels may be prepared in
      anthropomorphic phantoms, to confirm unique patient dose distributions.

PMID- 9276379
TI  - Beam shaping for conformal fractionated stereotactic radiotherapy: a modeling
      study.
AB  - PURPOSE: The patient population treated with fractionated stereotactic
      radiotherapy (SRT) is significantly different than that treated with stereotactic
      radiosurgery (SRS). Generally, lesions treated with SRT are larger, less
      spherical, and located within critical regions of the central nervous system;
      hence, they offer new challenges to the treatment planner. Here a simple, cost
      effective, beam shaping system has been evaluated relative to both circular
      collimators and an ideal dynamically conforming system for effectiveness in
      providing conformal therapy for these lesions. METHODS AND MATERIALS: We have
      modeled a simple system for conformal arc therapy using four independent jaws.
      The jaw positions and collimator angle are changed between arcs but held fixed
      for the duration of each arc. Eleven previously treated SRT cases have been
      replanned using this system. The rectangular jaw plans were then compared to the
      original treatment plans which used circular collimators. The plans were
      evaluated with respect to tissue sparing at 100%, 80%, 50%, and 20% of the
      prescription dose. A plan was also done for each tumor in which the beam aperture
      was continuously conformed to the beams eye view projection of the tumor. This
      was used as an ideal standard for conformal therapy in the absence of fluence
      modulation. RESULTS: For tumors with a maximum extent of over 3.5 cm the
      rectangular jaw plans reduced the mean volume of healthy tissue involved at the
      prescription dose by 57% relative to the circular collimator plans. The ideal
      conformal plans offered no significant further improvement at the prescription
      dose. The relative advantage of the rectangular jaw plans decreased at lower
      isodoses so that at 20% of the prescription dose tissue involvement for the
      rectangular jaw plans was equivalent to that for the circular collimator plans.
      At these isodoses the ideal conformal plans gave substantially better tissue
      sparing. CONCLUSION: A simple and economical field shaping device has been shown
      to provide all of the beam shaping advantage of a hypothetical ideal dynamically
      conforming system at the prescription level. This system may be immediately
      implemented in the clinic. It offers a substantial advantage over the currently
      used circular collimators in the high dose region with equivalent performance in
      the low dose region.

PMID- 9276380
TI  - Field margin reduction using intensity-modulated x-ray beams formed with a
      multileaf collimator.
AB  - PURPOSE: In axial, coplanar treatments with multiple fields, the superior and
      inferior ends of a planning target volume (PTV) are at risk to get underdosed due
      to the overlapping penumbras of all treatment fields. We have investigated a
      technique using intensity modulated x-ray beams that allows the use of small
      margins for definition of the superior and inferior field borders while still
      reaching a minimum PTV-dose of 95% of the isocenter dose. METHODS AND MATERIALS:
      The applied intensity modulated beams, generated with a multileaf collimator,
      include narrow (1.1-1.6 cm) boost fields to increase the dose in the superior and
      inferior ends of the PTV. The benefits of this technique have been assessed using
      3D treatment plans for 10 prostate cancer patients. Treatment planning was
      performed with the Cadplan 3D planning system (Varian-Dosetek). Dose calculations
      for the narrow boost fields have been compared with measurements. The application
      of the boost fields has been tested on the MM50 Racetrack Microtron (Scanditronix
      Medical AB), which allows fully computer-controlled setup of all involved
      treatment fields. RESULTS: Compared to our standard technique, the superior
      inferior field length can be reduced by 1.6 cm, generally yielding smaller
      volumes of rectum and bladder in the high dose region. For the narrow boost
      fields, calculated relative dose distributions agree within 2% or 0.2 cm with
      measured dose distributions. For accurate monitor unit calculations, the phantom
      scatter table used in the Cadplan system had to be modified using measured data
      for square fields smaller than 4 x 4 cm2. The extra time needed at the MM50 for
      the setup and delivery of the boost fields is usually about 1 min. CONCLUSION:
      The proposed use of intensity modulated beams yields improved conformal dose
      distributions for treatment of prostate cancer patients with a superior-inferior
      field size reduction of 1.6 cm. Treatments of other tumor sites can also benefit
      from the application of the boost fields.

PMID- 9276381
TI  - The influence of x-ray energy on lung dose uniformity in total-body irradiation.
AB  - PURPOSE: In this study we examine the influence of x-ray energy on the uniformity
      of the dose within the lung in total-body irradiation treatments in which partial
      transmission blocks are used to control the lung dose. METHODS AND MATERIALS: A
      solid water phantom with a cork insert to simulate a lung was irradiated by x
      rays with energies of either 6, 10, or 18 MV. The source to phantom distance was
      3.9 meters. The cork insert was either 10 cm wide or 6 cm wide. Partial
      transmission blocks with transmission factors of 50% were placed anterior to the
      cork insert. The blocks were either 8 or 4 cm in width. Kodak XV-2 film was
      placed in the midline of the phantom to record the dose. Midplane dose profiles
      were measured with a densitometer. RESULTS: For the 10 cm wide cork insert the
      uniformity of the dose over 80% of the block width varied from 6.6% for the 6 MV
      x-rays to 12.2% for the 18 MV x-rays. For the 6 cm wide cork insert the
      uniformity was comparable for all three x-ray energies, but for 18 MV the central
      dose increased by 9.4% compared to the 10 cm wide insert. CONCLUSION: Many
      factors must be considered in optimizing the dose for total-body irradiation.
      This study suggests that for AP/PA techniques lung dose uniformity is superior
      with 6 MV irradiation. The blanket recommendation that the highest x-ray energy
      be used in TBI is not valid for all situations.

PMID- 9276382
TI  - Comparison between normal tissue reactions and local tumour control in head and
      neck cancer patients treated by definitive radiotherapy: regarding IJROBP 35:455
      462; 1996.

PMID- 9276383
TI  - In response to Drs. Goitein and Niemierko.

PMID- 9276384
TI  - Is there a future for neutron capture therapy?

PMID- 9276385
TI  - "Permanent iodine-125 (I-125) boost after teletherapy in primary cancers of the
      nasopharynx is safe and highly effective: long-term results".

PMID- 9276386
TI  - Comparison of screening methods for detection of extended-spectrum beta
      lactamases and their prevalence among blood isolates of Escherichia coli and
      Klebsiella spp. in a Belgian teaching hospital.
AB  - Using a set of 33 well-defined extended-spectrum beta-lactamase (ESBL)-producing
      strains of Escherichia coli and Klebsiella pneumoniae, we compared three
      screening methods for ESBL detection: (i) a double-disk synergy test, (ii) a
      three-dimensional test (both the double-disk synergy test and the three
      dimensional test were performed with ceftriaxone, ceftazidime, aztreonam, and
      cefepime), and (iii) the Etest ESBL screen (AB Biodisk, Solna, Sweden), based on
      the recognition of a reduction in the ceftazidime MIC in the presence of
      clavulanic acid. In the double-disk test, all four indicator antibiotics scored
      equally and 31 of the 33 reference strains were recognized. In the three
      dimensional test, ceftriaxone was the only satisfactory indicator and 30 ESBL
      positive strains were detected by this antibiotic. Both systems produced two
      false-positive results with cefepime. With the Etest ESBL screen, 15 of 16 TEM
      related and 11 of 16 SHV-related ESBL-producing strains scored positive. In 10
      cases the clavulanic acid on one end of the strip interfered with the MIC
      determination for ceftazidime, which was read on the opposite end. This MIC had
      to be determined with an extra ceftazidime-only strip. No false-positive results
      were noted. Eighty-six blood isolates of E. coli and Klebsiella species were
      screened for ESBL expression by the double-disk and three-dimensional tests, both
      with ceftriaxone. Six strains with suspicious antibiogram phenotypes also gave
      positive results by the double-disk test. One E. coli strain remained undetected
      by the three-dimensional test. Identification of the enzymes suspected of being
      ESBLs by isoelectric focusing (all strains) and DNA sequencing (1 strain)
      confirmed the screening test results except for one Klebsiella oxytoca strain,
      which proved to be a hyperproducer of its chromosomal enzyme and which also had a
      negative Etest score. The five true ESBL producers were all confirmed by the
      Etest ESBL screen. Pulsed-field gel electrophoresis proved that the E. coli
      strains were unrelated, but that two of the three K. pneumoniae strains were
      closely related.

PMID- 9276387
TI  - Serological responses to Ehrlichia equi, Ehrlichia chaffeensis, and Borrelia
      burgdorferi in patients from New York State.
AB  - Serological testing at the New York State Department of Health for human
      granulocytic ehrlichiosis in the residents of Westchester County, N.Y., was
      performed with specimens from 176 patients by the indirect fluorescent-antibody
      (IFA) technique with Ehrlichia equi MRK-infected neutrophils. To understand
      whether human monocytotropic ehrlichiosis also occurs in this northeastern
      geographic region, specimens were also tested for antibodies to Ehrlichia
      chaffeensis Arkansas. Screening tests and immunoblots for Lyme disease (Borrelia
      burgdorferi infection) were also performed. Thirty-two patients had antibodies
      only to E. equi and 21 patients had antibodies to both E. equi and E.
      chaffeensis, whereas 12 patients had only E. chaffeensis antibodies by the IFA
      technique. The remaining patients did not have antibodies to either ehrlichia.
      Eighteen serum samples from 13 of these patients were coded and sent to the
      Ehrlichia Research Laboratory (Baltimore, Md.) for repeat analysis by the IFA
      test and for E. equi and E. chaffeensis immunoblots. Immunoblot analysis for E.
      equi in samples with positive IFA test results confirmed the results for eight of
      the nine specimens. Immunoblot analyses for E. chaffeensis were negative for all
      18 serum samples. Borrelia-reactive antibodies were found in sera both from
      patients with granulocytic ehrlichiosis and from patients with monocytotropic
      ehrlichiosis from New York State. Our results suggest that E. equi antigen is an
      appropriate substrate for identifying human granulocytic ehrlichiosis. E.
      chaffeensis antigen lacks appropriate sensitivity to serve as a surrogate
      substrate for the detection of human granulocytic ehrlichiosis and should be used
      solely for the diagnosis of human monocytotropic ehrlichiosis. Heat shock
      proteins may, in some cases, cause cross-reactivity between B. burgdorferi and
      ehrlichiae.

PMID- 9276388
TI  - Immunohistologic identification of Aspergillus spp. and other hyaline fungi by
      using polyclonal fluorescent antibodies.
AB  - Isolation and identification of pathogenic Aspergillus and Fusarium spp. from
      clinical materials provide the most accurate means for establishing a diagnosis
      of infections by these molds. Such efforts, however, are not always successful.
      Histologic diagnosis also has its limitations. In vivo the hyphae of Aspergillus
      and Fusarium spp. are very similar and their in situ manifestations are not
      pathognomonic. To improve the histologic diagnosis of infections by Aspergillus
      and Fusarium species, we developed polyclonal fluorescent-antibody reagents to
      Aspergillus fumigatus and Fusarium solani and evaluated their diagnostic
      utilities. Our studies revealed that A. fumigatus and F. solani share epitopes
      not only with one another but also with other Aspergillus and Fusarium spp. as
      well as with Paecilomyces lilacinus and Pseudallescheria boydii. Adsorption of
      the A. fumigatus conjugate with cells of Fusarium proliferatum and F. solani and
      F. solani antiserum with cells of Aspergillus flavus resulted in reagents that
      distinguished Aspergillus spp. from Fusarium spp. but that still cross-stained P.
      lilacinus and P. boydii. Adjunctive use of a specific P. boydii conjugate enabled
      the identification of Aspergillus spp., Fusarium spp., P. lilacinus, and P.
      boydii in formalin-fixed tissue sections from 19 humans with culture-proven cases
      of mycotic infection.

PMID- 9276389
TI  - Evaluation of spoligotyping in a study of the transmission of Mycobacterium
      tuberculosis.
AB  - Spoligotyping (for spacer oligotyping) is an easy, economical, and rapid way of
      typing Mycobacterium tuberculosis complex strains with the DR spacer markers (J.
      Kamerbeek et al., J. Clin. Microbiol. 35:907-914, 1997; D. van Soolingen et al.,
      33:3234-3248, 1995). The stability of the markers was demonstrated by showing
      that all the Mycobacterium bovis BCG strains tested gave the same spoligotyping
      pattern. None of the 42 atypical mycobacterial strains tested gave a
      spoligotyping signal, indicating the specificity of the technique for M.
      tuberculosis complex. The utility of the spoligotyping method was demonstrated by
      analyzing 106 isolates of M. tuberculosis obtained over 1 year in three Paris
      hospitals. The results obtained by this technique were compared to those obtained
      by Torrea et al. (G. Torrea et al., J. Clin. Microbiol. 34:1043-1049, 1996) by
      IS6110-based restriction fragment length polymorphism (RFLP) analysis. Strains
      from patients with epidemiological relationships that were in the same IS6110
      RFLP cluster were also in the same spoligotyping group. Spoligotyping was more
      discriminative than RFLP analysis for strains with one or two copies of IS6110.
      RFLP analysis did not discriminate between the nine strains with one or two
      IS6110 bands with no known epidemiological relation, whereas spoligotyping
      distinguished between eight different types. IS6I10-RFLP analysis split some of
      the spoligotyping clusters, particularly when the IS6110 copy number was high.
      Therefore, we propose a strategy for typing M. tuberculosis strains in which both
      markers are used.

PMID- 9276390
TI  - Comparison of PCR and culture to the indirect fluorescent-antibody test for
      diagnosis of Potomac horse fever.
AB  - Potomac horse fever is an acute systemic equine disease caused by Ehrlichia
      risticii. Currently, serologic methods are widely used to diagnose this disease.
      However, serologic methods cannot determine whether the horse is presently
      infected or has been exposed to ehrlichial antigens in the past. The purpose of
      the present study was to compare the sensitivities of the nested PCR and cell
      culture with that of the indirect fluorescent-antibody (IFA) test for the
      diagnosis of Potomac horse fever. Blood and fecal specimens serially collected
      from a pony experimentally infected with E. risticii Maryland, blood specimens
      serially collected from mice inoculated with E. risticii Ohio 380, and blood
      and/or fecal specimens collected from 27 horses which had clinical signs
      compatible with Potomac horse fever were examined. These horses resided in
      Kentucky, Indiana, Pennsylvania, and Vermont. The IFA test titer became positive
      after 6 days postinoculation (p.i.) for the pony. A culture of the blood of the
      pony was positive for E. risticii starting on day 1 and was positive through day
      28 p.i. By the nested PCR, E. risticii was detectable in the blood and feces of
      the pony starting on day 1 and was detectable through day 32 p.i. E. risticii was
      detected in the blood of subclinically infected mice by the nested PCR. Twenty
      two clinical specimens were seropositive for E. risticii by the IFA test, with
      titers ranging from 1:20 to 1:1,280. E. risticii was cultured from 95% (20 of 21)
      of seropositive clinical blood specimens. E. risticii was detected in the blood
      by PCR in 81% (17 of 20) of the culture-positive clinical specimens. The study
      indicated that the nested PCR is as sensitive as culture for detecting infection
      with E. risticii.

PMID- 9276391
TI  - Immunoreactivity of a 38-kilodalton Penicillium marneffei antigen with human
      immunodeficiency virus-positive sera.
AB  - Penicillium marneffei produced and secreted a 38-kDa antigen that appeared to be
      specific for this dimorphic fungus. This component could not be detected in
      antigenic extracts of Histoplasma capsulatum, Cryptococcus neoformans,
      Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus, Aspergillus
      terreus, Candida albicans, and two other species of Penicillium by immunoblot
      analysis against the sera from patients with culture-confirmed penicilliosis
      marneffei. Antibody reactive with this antigen was found in a large proportion of
      human immunodeficiency virus (HIV)-positive patients, indicating a presumptive
      diagnosis of P. marneffei infection. A small number of asymptomatic HIV
      seropositive patients and HIV-seropositive patients with other fungal infections
      were also found to be positive by this analysis, suggesting that subclinical or
      mixed fungal infections involving P. marneffei are not uncommon.

PMID- 9276392
TI  - Effects of storage temperature and time on qualitative and quantitative detection
      of cytomegalovirus in blood specimens by shell vial culture and PCR.
AB  - Cytomegalovirus (CMV) infectious titers and DNA levels were determined by
      quantitative shell vial culture and quantitative-competitive PCR with blood
      samples from 10 renal transplant recipients with active CMV infection. Blood
      samples were stored at either room temperature or 4 degrees C and were processed
      at intervals of 0, 6, 24, 48, and 72 h. All samples were culture and PCR positive
      at baseline. Whereas the sensitivity of shell vial culture progressively
      declined, with only 55% positive at 24 h and 10% positive at 48 h, all samples
      remained PCR positive at all time points. Furthermore, the infectious titer
      diminished by 83 to 91% by 24 h compared to that at baseline (P < 0.0001), but
      quantitative DNA levels did not decline over time. Storage temperature had no
      significant effect on either infectious titer or DNA levels.

PMID- 9276393
TI  - Rapid detection of mycobacteria in clinical specimens by using the automated
      BACTEC 9000 MB system and comparison with radiometric and solid-culture systems.
AB  - Recovery rates of acid-fast bacilli (AFB) and the mean time to their detection
      from clinical specimens were determined by using the fluorescent BACTEC 9000 MB
      system. Data were compared to those assessed by the radiometric BACTEC 460 system
      and by cultivation on solid media. A total of 3,095 specimens were processed with
      N-acetyl-L-cysteine-NaOH by two laboratories. The contamination rates for the
      BACTEC 9000 MB system were 6.8% (center 1) and 9.8% (center 2). A total of 451
      mycobacterial isolates were detected (Mycobacterium tuberculosis complex, n =
      296; nontuberculous mycobacteria [NTM], n = 155). These isolates originated from
      94 (20.8%) smear-positive and 357 (79.2%) smear-negative specimens. The BACTEC
      9000 MB system was significantly better than solid media (P < 0.05) in detecting
      AFB, but it was less efficient than the radiometric system (P < 0.01). The BACTEC
      9000 MB system plus solid media (combination A) recovered 393 (87.1%) of the
      isolates, while the BACTEC 460 system plus solid media (combination B) detected
      430 (95.3%) of all AFB isolates. Between combination A and B there was no
      statistically significant difference for the detection of isolates from smear
      positive specimens (P > 0.05), in contrast to the recovery of AFB from smear
      negative specimens for M. tuberculosis complex, P < 0.05; for NTM, P < 0.01). The
      mean time to detection of M. tuberculosis complex was 12.2 days for smear
      positive specimens and 18.1 days for smear-negative specimens with the BACTEC
      9000 MB system; 9.3 and 15.6 days, respectively, with the BACTEC 460 system; and
      21.2 and 28.4 days, respectively, with solid media. For NTM, the average
      detection times were 15.1, 17.3, and 31.3 days by the three methods,
      respectively. In conclusion, the BACTEC 9000 MB system is a rapid, less labor
      intensive detection system which allows for higher levels of recovery of AFB than
      solid media. There is no risk of cross contamination, which is known to be the
      case for the BACTEC 460 system, and data management is greatly facilitated. As a
      whole, however, the BACTEC 9000 MB system should only be used in conjunction with
      solid media.

PMID- 9276394
TI  - Recognition of a Nocardia transvalensis complex by resistance to aminoglycosides,
      including amikacin, and PCR-restriction fragment length polymorphism analysis.
AB  - Amikacin resistance, rare among nocardiae, was observed in 58 clinical isolates
      of nocardiae. All of these isolates hydrolyzed hypoxanthine, and 75 to 100%
      utilized citrate, D-galactose, and D-trehalose as sole carbon sources. Based on
      utilization of I-erythritol, D-glucitol, i-myo-inositol, D-mannitol, and ribitol
      and susceptibility to amoxicillin-clavulanic acid, the 58 isolates were separable
      into four groups. One group was negative for I-erythritol and ribitol and
      included all the isolates belonging to Nocardia asteroides complex antibiogram
      type IV. The remaining three groups were positive for I-erythritol and ribitol
      and were grouped within Nocardia transvalensis. The group that included the type
      strain was designated N. transvalensis sensu stricto, and the other two groups
      were designated new taxons 1 and 2. PCR-restriction fragment length polymorphism
      (RFLP) analysis of a 439-bp segment of the 65-kDa heat shock protein gene with
      XhoI and HinfI produced identical patterns for 53 (91%) and 58 (100%) isolates,
      respectively, and differentiated them from all other Nocardia taxa. NarI- and
      HaeIII-derived RFLP patterns clearly differentiated each of the four
      biochemically defined taxa. These four groups were also distinguishable by using
      the chromogenic substrates in Dade MicroScan test panels. By high-performance
      liquid chromatography, these isolates exhibited the same unique mycolic acid
      ester elution patterns that differed from those of all other clinically
      significant nocardiae. Gas-liquid chromatographic analysis of fatty acids also
      produced similar patterns for all isolates that distinguished them from all other
      Nocardia taxa, but did not differentiate the four taxa within the complex. We
      propose the designation N. transvalensis complex for these four groups of
      nocardiae, pending further genetic evaluation.

PMID- 9276395
TI  - Molecular epidemiology of Cryptococcus neoformans in Brazil and the United
      States: evidence for both local genetic differences and a global clonal
      population structure.
AB  - Little is known about the global molecular epidemiology of the human pathogenic
      fungus Cryptococcus neoformans. We studied 51 clinical and environmental (pigeon
      excreta) isolates from two cities in Brazil (Belo Horizonte and Rio de Janeiro)
      by analyzing their carbon assimilation patterns, electrophoretic karyotypes,
      restriction fragment length polymorphisms (RFLPs) with the C. neoformans
      repetitive element-1 (CNRE-1), and URA5 sequences. Results were compared to those
      previously obtained for isolates from New York City by the same DNA typing
      methods. Computer-assisted analysis of RFLPs and contour-clamped homogeneous
      electrophoresis (CHEF) patterns and URA5 sequences was performed to generate
      dendrograms. Some environmental and clinical isolates were found to be
      indistinguishable by CHEF, CNRE-1 RFLP, and URA5 sequence analyses. Similarly,
      some isolates from Rio de Janeiro and Belo Horizonte were indistinguishable by
      the three DNA typing techniques. Overall, Brazilian isolates appeared to be less
      heterogeneous by DNA analysis than isolates from other regions. Several Brazilian
      isolates were highly related to New York City isolates. Phylogenetic analysis of
      the sequences obtained for the Brazilian isolates and those obtained for New York
      City isolates was congruent with the dendrogram generated from the CNRE-1 RFLP
      data. In summary our results indicate (i) that the discriminatory power of the
      DNA typing method differs for Brazilian and New York City strains, with the order
      being CNRE-1 RFLP analysis > URA5 sequence analysis > CHEF analysis and CHEF
      analysis > URA5 sequence analysis > CNRE-1 RFLP analysis, respectively; (ii) that
      there are differences in local genetic diversity for Brazilian and New York City
      isolates; (iii) that there is additional evidence linking clinical isolates to
      those in pigeon excreta; and (iv) that some isolates from Brazil and New York
      City are closely related, consistent with the global dispersal of certain
      pathogenic strains.

PMID- 9276396
TI  - Comparison of radioimmunoassay and enzyme-linked immunoassay methods for
      detection of Histoplasma capsulatum var. capsulatum antigen.
AB  - The purpose of this study was to compare the conventional radioimmunoassay (RIA)
      to an enzyme-linked immunoassay (EIA) for the measurement of Histoplasma antigen
      in banked urine specimens. A correlation between the two methods would allow the
      EIA to be used as a nonradioactive alternative to the established 125I RIA. The
      study used stored urine from patients diagnosed with histoplasmosis during an
      outbreak in Indianapolis which began in 1988. Control specimens from healthy
      adults, patients with other fungal infections, urinary tract infections, or
      nonfungal pneumonia were also tested. Both the RIA and EIA were run concurrently.
      The RIA system measured antigen levels of 0.4 to 27.0 RIA units, while the EIA
      measured antigen levels of 0.6 to 20.1 units. Both the EIA and RIA detected
      measurable antigen levels in urine from 50 of 56 patients (89%) with disseminated
      disease and 11 of 30 patients (37%) with self-limiting disease. One of 96 control
      specimens, from a patient with paracoccidioidomycosis, was positive with both
      systems. Antigen levels measured by EIA correlated well with those measured by
      the established RIA method (correlation coefficient, 0.974). The EIA is an
      acceptable alternative to the RIA for measuring Histoplasma antigen levels in
      urine specimens.

PMID- 9276397
TI  - Prevalence of Bartonella species in domestic cats in The Netherlands.
AB  - Cats have been shown to provide the only known reservoir of Bartonella henselae,
      the causative agent of cat scratch disease. To determine the prevalence of
      Bartonella bacteremia and antibodies in Dutch cats, blood samples from 113 cats
      from shelters (sheltered cats), 50 pet cats, and 25 specific-pathogen-free (SPF)
      cats were analyzed. Culture and subsequent PCR-restriction fragment length
      polymorphism (RFLP) analysis of the 16S-23S rRNA intergenic region and 16S rRNA
      gene PCR-hybridization assays revealed a prevalence of Bartonella bacteremia in
      22% of the sheltered cats and showed no bacteremia in the SPF cats. Three spacer
      RFLP types were found: types A, B, and G, with type B being predominant over
      types A and G. An important finding was the existence of mixtures of different
      Bartonella species. Bartonella DNA was detected in 7 of 27 DNA extracts from
      fleas combed from the sheltered cats (26%). Seropositivity was 50% for sheltered
      cats and 56% for pet cats, as determined by a B. henselae enzyme-linked
      immunoassay.

PMID- 9276398
TI  - Comparison of the hybrid capture tube test and PCR for detection of human
      papillomavirus DNA in cervical specimens.
AB  - The strong association of human papillomavirus (HPV) and cervical cancer makes it
      important to study HPV detection methods that may play a role in cervical cancer
      screening. We compared two DNA methods that are commonly used for HPV research in
      the United States: the MY09/MY11 L1 consensus primer PCR-based test and the first
      generation Hybrid Capture tube method (HCT). Laboratory assays by each method
      were performed with 596 cervicovaginal specimens collected from participants in a
      large cohort study conducted in Portland, Oreg. Included were 499 specimens from
      women whose cytology was normal and 97 specimens from women with squamous
      intraepithelial lesions (SILs). The overall HPV DNA positivity for known types
      was 22.5% by PCR compared to 13.6% by HCT. When the analysis was restricted to
      the 14 HPV types detectable by both methods, the sensitivity of HCT, with PCR
      used as the standard for HPV status, was higher for specimens from women with
      concurrent SILs (81.0%) than for specimens from women with normal cytology
      (46.7%). Among specimens testing positive by both methods, 97.2% of the time the
      two methods agreed on whether specimens were positive for cancer-associated HPV
      types. Both of these HPV test methods provide information that supplements the
      information provided by the Pap smear. The PCR method has higher analytic
      sensitivity than HCT in detecting HPV, but HCT may be helpful in identifying
      women with concurrent SILs.

PMID- 9276399
TI  - Comparative evaluation of modified trichrome and Uvitex 2B stains for detection
      of low numbers of microsporidial spores in stool specimens.
AB  - At present, the laboratory diagnosis of intestinal infections caused by
      microsporidia depends on the detection of the typical spores either with a
      modified trichrome stain (MTS) or by staining with fluorochromes. The purpose of
      the present study was (i) to compare staining with MTS (MTS method) and the
      staining with the fluorochrome Uvitex 2B (U2B method) with respect to their
      sensitivities and specificities, particularly in the presence of low numbers of
      spores, and (ii) to evaluate their reliabilities under routine laboratory
      conditions. First, 30 negative human stool specimens as well as 30 specimens
      enriched with a low concentration of microsporidial spores were examined. The U2B
      and MTS methods detected 27 and 30, of the positive samples, respectively (95%
      confidence intervals for sensitivity, 0.73 to 0.98 for the U2B method and 0.88 to
      1.00 for the MTS method) without yielding false-positive results (95% confidence
      intervals for specificity, 0.88 to 1.00 for the MTS and U2B methods). In
      addition, analysis of serial dilutions of 17 stool specimens from AIDS patients
      containing microsporidia revealed comparable detection thresholds (P = 0.52) for
      both methods. Finally, 40 slides prepared from one stool specimen containing very
      few microsporidia and 40 negative slides were included in the routine diagnostic
      program during 1 month in order to monitor laboratory handling and run-to-run
      variations. Again, both methods exhibited comparable sensitivities (95%
      confidence intervals, 0.83 to 0.99 for the MTS method and 0.91 to 1.00 for the
      U2B method) and specificities (95% confidence intervals, 0.91 to 1.00 for the MTS
      and U2B methods). In conclusion, MTS and U2B methods are equally useful in the
      diagnosis of microsporidiosis. However, since detection thresholds for both
      methods differed considerably in all diluted stool specimens, performance of a
      combination of both methods may be more sensitive than the performance of only
      one procedure in the event of very low numbers of microsporidial spores.

PMID- 9276400
TI  - Characterization of Scedosporium prolificans clinical isolates by randomly
      amplified polymorphic DNA analysis.
AB  - Fingerprinting by randomly amplified polymorphic DNA (RAPD) analysis was used to
      differentiate Scedosporium prolificans isolates. A total of 59 arbitrary primers
      were screened with six unrelated S. prolificans isolates, and a panel of 12
      primers was selected. The 12 primers were then used to detect DNA polymorphisms
      among 17 S. prolificans isolates from 11 patients with systemic S. prolificans
      infections diagnosed in three hospitals located in geographically different areas
      of Spain. Eight patients were diagnosed with S. prolificans infection in a single
      institution over a 6-year period, and two other patients were diagnosed with S.
      prolificans infection in a different hospital over a 1-year period. No single
      primer allowed for the discrimination of all the isolates from different
      patients, but this was possible by combining the RAPD patterns from three primers
      (UBC 701, AB1.08, and AB1.11 or UBC 701, AB1.08, and UBC 707). However, multiple
      isolates from the same patient were identical. In this study, we also compared a
      visual method and a computerized method for the analysis of the RAPD patterns.
      Both methods were satisfactory and gave few discordances, but given the
      advantages and disadvantages of each method, both systems should be used
      together. RAPD analysis provided a fast and economical means of typing S.
      prolificans isolates, with a high level of discrimination among unrelated
      isolates. Typing by RAPD analysis confirmed that the S. prolificans infections
      were epidemiologically unrelated.

PMID- 9276401
TI  - Rapid detection and typing of herpes simplex virus DNA in clinical specimens by
      the hybrid capture II signal amplification probe test.
AB  - A second-generation signal amplification, nucleic acid-based test for the rapid
      detection and typing of herpes simplex virus (HSV) DNA was developed and
      evaluated with artificial and clinical specimens. The analytical sensitivity of
      the Hybrid Capture II (HC II) HSV DNA assay was determined by testing either
      cloned HSV DNA or total genomic HSV DNA titrations and resulted in detection
      thresholds of between 5 x 10(3) and 1 x 10(4) copies per assay. Specificity was
      assessed by testing a panel of bacteria and viruses commonly found in the female
      genital tract. Sensitivity was assessed by testing 112 ulcerative genital lesions
      by the HC II assay and comparing the results to those obtained by routine cell
      culture. Discrepant results were resolved by PCR testing. After resolution of the
      discrepant results, the sensitivity of the HC II assay compared to the consensus
      result (the results of two of three tests, the HC II assay, culture, and PCR,
      were in agreement) was 93.2% (41 of 44 specimens), and the specificity was 100%
      (60 of 60 specimens). Culture gave a sensitivity of 84.1% (37 of 44 specimens)
      and a specificity of 100% (60 of 60 specimens) compared to the consensus result.
      The results of HSV typing by the HC II assay and culture agreed in all cases. The
      HC II assay is a rapid and accurate assay for detecting and typing HSV types 1
      and 2, with a sensitivity comparable to that of culture and greater ease of use
      than culture.

PMID- 9276402
TI  - Isolation of verotoxin-producing Escherichia coli O-rough:K1:H7 from two patients
      with traveler's diarrhea.
AB  - Two Escherichia coli O-rough:K1:H7 strains producing verotoxin 1 that were
      isolated from stool samples of two travelers with diarrhea who consulted our
      clinic after trips to the Indian Subcontinent and Central America were
      characterized. Both strains were sorbitol negative, the same phenotype presented
      by E. coli O157:H7, but in contrast they were beta-glucuronidase positive. Low
      frequency restriction analysis of chromosomal DNA and pulsed-field gel
      electrophoresis and repetitive extragenic palindrome-PCR showed that both strains
      were epidemiologically related. The illness was self-limited in both cases but
      involved long-duration, watery diarrhea (10 to 50 days) accompanied by abdominal
      cramps and flatulence. This serotype should be taken into account as a possible
      cause of traveler's diarrhea.

PMID- 9276403
TI  - Serological cross-reactions between Bartonella and Chlamydia species:
      implications for diagnosis.
AB  - Diagnosis of Chlamydia or Bartonella infections continues to rely mainly on
      serology. However, serological cross-reactions between members of these genera
      have recently been described. Sera from eight patients originally diagnosed as
      having Chlamydia pneumoniae endocarditis reacted with both Chlamydia sp. and
      Bartonella quintana antigens (microimmunofluorescence technique). Adsorption of
      sera with B. quintana or C. pneumoniae antigens removed anti-C. pneumoniae
      antibodies, whereas adsorption with C. pneumoniae antigens did not change
      antibody titers to B. quintana. Western blot analysis confirmed the presence of
      cross-reacting antigens and showed antibody patterns in all sera to be compatible
      with a Bartonella infection. These patients were therefore probably suffering
      from Bartonella-induced rather than Chlamydia-induced endocarditis. In contrast,
      sera from 10 patients presumed to be suffering from C. pneumoniae pneumonia did
      not display anti-B. quintana antibodies, although cross-reacting antigens were
      revealed by Western blotting. This work highlights the possibility that cases of
      infective Bartonella endocarditis are erroneously diagnosed as chlamydial
      infections.

PMID- 9276404
TI  - Latency and reactivation of JC virus in peripheral blood of human
      immunodeficiency virus type 1-infected patients.
AB  - JC virus (JCV) acts as an opportunistic virus in immunocompromised human
      immunodeficiency virus type 1 (HIV-1)-infected patients. The role of peripheral
      blood cells in central nervous system invasion, before the onset of progressive
      multifocal leukoencephalopathy (PML), remains controversial. In order to clarify
      JCV latency or reactivation status in peripheral blood, 72 HIV-1-infected
      patients were studied, together with 7 HIV-1-positive PML patients and 50 blood
      donors. Blood leukocytes, plasma, and B lymphocytes were investigated by two
      complementary DNA amplification procedures within the early T and late VP1 JCV
      genes and two reverse transcription techniques for the detection of corresponding
      early transcripts and mRNAs. JCV DNA was detected in 40.3% of the HIV-1-infected
      patients but only 8% of the blood donors (P < 0.001). Leukocytes represented
      82.7% of the positive samples, but plasma from 12 patients (41.4%) contained JCV
      DNA. B lymphocytes seemed to be involved in the natural history of JCV but did
      not represent the unique cell target. JCV DNA was intermittently found in blood,
      and JCV mRNAs for VP1 capsid protein were detected exclusively in one PML
      patient. Such observations demonstrate that JCV, when detected in blood, does not
      undergo active multiplication. They support the JCV hematogenous spread
      hypothesis, but do not indicate any direct link between peripheral virus and
      dissemination in the central nervous system at the time of immunodepression.

PMID- 9276405
TI  - Use of synthetic antigens improves detection by enzyme-linked immunosorbent assay
      of antibodies against abortigenic Chlamydia psittaci in ruminants.
AB  - Synthetic peptide antigens were prepared for use in enzyme-linked immunosorbent
      assays (ELISAs) to detect serum antibodies against abortigenic strains of
      Chlamydia psittaci in livestock. Peptide antigens were identified with C.
      psittaci B577-immune sera by solid-phase scanning of overlapping octapeptides of
      variable domains (VDs) of the major outer membrane protein of C. psittaci serovar
      1 (omp1 type C. psittaci B577). Two VD 4 regions and one VD 2 region were
      strongly reactive with all C. psittaci B577 antisera. Peptides encompassing these
      regions were synthesized with biotin and a serine-glycine-serine-glycine spacer
      at the N terminus and were attached to streptavidin-coated microtiter plates. In
      direct ELISAs with these plates, the synthetic peptides reacted with C. psittaci
      B577 antisera, but not with sera from specific-pathogen-free animals. Serum
      specimens from 40 sheep and 40 cattle, obtained from herds with abortion
      problems, were screened for antibodies by these C. psittaci B577 peptide ELISAs
      and an ELISA with recombinant, genus-specific Chlamydia lipopolysaccharide (LPS)
      antigen. Results from these newly developed ELISAs were compared to those from
      the reference C. psittaci B577 elementary body (EB) ELISA and the Chlamydia
      complement fixation test (CFT). The C. psittaci B577 peptide ELISAs, the LPS
      ELISA, and the EB ELISA correctly identified the presence or absence of
      antibodies against chlamydiae in all sheep and bovine sera. The Chlamydia CFT,
      which is the most widely accepted serodiagnostic method for chlamydial infections
      in animals, correctly identified the presence or absence of antibodies against
      chlamydiae in only 78 and 4.9% of sheep and bovine sera, respectively. These
      results suggest that the C. psittaci B577-peptide and Chlamydia LPS ELISAs are
      superior for the serodiagnosis of ruminant infections with abortigenic
      chlamydiae, since they are more sensitive than the CFT, they are easy to
      standardize, and they use readily available synthetic antigens instead of
      organism-derived CFT antigen.

PMID- 9276407
TI  - Granulocytic ehrlichiosis in two dogs in Switzerland.
AB  - This case report describes two dogs with granulocytic ehrlichiosis. Dog 1 was a
      male Labrador retriever with clinical signs of lymphosarcoma. Dog 2 was a female
      Airedale terrier, whose clinical signs included apathy, pyrexia, diarrhea, and
      abdominal pain. Examination of blood smears revealed Ehrlichia organisms in the
      neutrophils of both dogs. There was thrombocytopenia in both dogs, and dog 2 also
      had leukopenia. In both dogs, bands of identical length were amplified from DNA
      of leukocytes via nested PCR. The bands had identical nucleotide sequences, which
      differed from the gene sequences of Ehrlichia equi and E. phagocytophila in three
      and two positions, respectively. Interestingly, the nucleotide sequence of the
      16S rRNA was 100% homologous to that of a human granulocytic ehrlichia.

PMID- 9276408
TI  - Identification and DNA fingerprinting of Legionella strains by randomly amplified
      polymorphic DNA analysis.
AB  - The randomly amplified polymorphic DNA (RAPD) technique was used in the
      development of a fingerprinting (typing) and identification protocol for
      Legionella strains. Twenty decamer random oligonucleotide primers were screened
      for their discriminatory abilities. Two candidate primers were selected. By using
      a combination of these primers, RAPD analysis allowed for the differentiation
      between all different species, between the serogroups, and further
      differentiation between subtypes of the same serogroup. The usefulness of RAPD
      analysis was also evaluated with outbreak-related clinical and environmental
      isolates previously typed by the restriction fragment length polymorphism
      technique. RAPD analysis proved to be as accurate as other genotypic methods,
      reproducible, and highly discriminatory and is a valuable new alternative to
      traditional fingerprinting and identification of Legionella species and strains.

PMID- 9276406
TI  - Molecular analysis of toxigenic Vibrio cholerae O139 Bengal strains isolated in
      Bangladesh between 1993 and 1996: evidence for emergence of a new clone of the
      Bengal vibrios.
AB  - Vibrio cholerae O139 Bengal emerged in 1992 and rapidly spread in an epidemic
      form, in which it replaced existing strains of V. cholerae O1 in Bangladesh
      during 1992 and 1993. The subsequent emergence of a new clone of V. cholerae O1
      of the El Tor biotype that transiently displaced the O139 vibrios during 1994 to
      1995 and the recent reemergence of V. cholerae O139 and its coexistence with the
      El Tor vibrios demonstrated temporal changes in the epidemiology of cholera in
      Bangladesh. We studied clonal diversity among V. cholerae O139 strains isolated
      from cholera patients and environmental surface water since their first
      appearance until their transient disappearance in 1994 as well as the O139
      strains that reemerged during 1995 to 1996 and were isolated in the capital Dhaka
      and four rural districts of Bangladesh to investigate the origin of the reemerged
      strains. Analysis of restriction fragment length polymorphisms in genes for
      conserved rRNA and cholera toxin (CT) (ctxA) or in DNA sequences flanking these
      genes revealed four different ribotypes and four different ctx genotypes among
      the 93 strains of V. cholerae O139 studied. Ribotypes I and II and ctx genotypes
      A through C were shared by strains isolated from the epidemic outbreak during
      1992 and 1993 in Bangladesh and India, ribotype III was represented by a single
      CT-negative O139 strain from Argentina, and 16 of 27 (59.2%) of the reemerged
      strains isolated during 1995 and 1996 belonged to a new ribotype of O139 vibrios
      designated ribotype IV. All 16 strains belonging to ribotype IV also belonged to
      a new ctx genotype (genotype 4). These results provide evidence for the emergence
      of a new clone of toxigenic V. cholerae O139 in Bangladesh. Further analysis of
      the rfb gene cluster by PCR revealed the absence of a large region of the O1
      specific rfb operon and the presence of an O139-specific genomic region in all
      O139 strains. The PCR amplicon corresponding to the rfaD gene of a CT-negative
      O139 strain from Argentina was smaller in length than those of the toxigenic O139
      strains but was identical to those of seven non-O1 and non-O139 strains. All O139
      strains except the CT-negative strain carried structural and regulatory genes for
      CT and toxin-coregulated pili (ctxA, tcpA, tcpI, and toxR). These results suggest
      that the O139 Bengal strains possibly emerged from an El Tor strain but that the
      CT-negative non-Bengal O139 strain might have emerged from a non-O1, non-O139
      strain. Thus, strains belonging to the O139 serogroup may have emerged from
      similar serotype-specific genetic changes in more than one progenitor strain of
      V. cholerae.

PMID- 9276409
TI  - Development of a rapid assay for detecting gyrA mutations in Escherichia coli and
      determination of incidence of gyrA mutations in clinical strains isolated from
      patients with complicated urinary tract infections.
AB  - The MICs of ofloxacin for 743 strains of Escherichia coli isolated from 1988 to
      1994 were determined by testing. The strains were from patients with urinary
      tract infections complicated by functional or anatomical disorders of the urinary
      tract. Those determined to be ofloxacin resistant (MIC, > or =12.5 microg/ml)
      comprised 3 of 395 strains (1.3%) from the 1988 to 1990 group, 2 of 166 strains
      (1.2%) from the 1991 to 1992 group, and 7 of 182 strains (3.8%) from the 1993 to
      1994 group. The incidence of resistant strains increased significantly during
      this period. The percentage of isolates with moderately decreased
      susceptibilities to ofloxacin (MIC, 0.39 to 3.13 microg/ml) also rose during the
      same period. To determine the incidence of gyrA mutations in urinary-tract
      derived strains of E. coli, we developed a simple and rapid assay based on PCR
      amplification of the region of the gyrA gene containing the mutation sites
      followed by digestion of the PCR product with a restriction enzyme. Using this
      assay, we examined all 182 strains isolated in 1993 and 1994 for the presence of
      mutations at Ser-83 and Asp-87 in the gyrA gene. Of these strains, 33 (18.1%) had
      mutations in the gyrA gene. The incidences of mutations at Ser-83, at Asp-87, and
      at both codons were 10.4 (19 strains), 4.4 (8 strains), and 3.3% (6 strains),
      respectively. To determine the correlation of the mutations in the gyrA gene with
      susceptibilities to quinolones (nalidixic acid, ofloxacin, norfloxacin, and
      ciprofloxacin), we further examined 116 strains for which the MICs of ofloxacin
      were > or =0.2 microg/ml that were chosen from the isolates in the 1988 to 1992
      group. The MICs of nalidixic acid for the strains without mutations at either Ser
      83 or Asp-87 were < or =25 microg/ml, whereas those for the strains with single
      mutations or double mutations were from 50 to >800 microg/ml. For the
      fluoroquinolones, significant differences in the distributions of the MICs were
      observed among the strains without mutations, with single mutations, and with
      double mutations. The accumulation of mutations in the gyrA gene was associated
      with an increase in fluoroquinolone resistance. Ofloxacin MICs for the majority
      of the strains with single and double mutations were 0.39 to 3.13 and 6.25 to 100
      microg/ml, respectively. This study demonstrates a chronological increase in the
      percentage of not only highly fluoroquinolone-resistant strains, corresponding to
      those with double mutations in the gyrA gene, but also strains with moderately
      decreased susceptibilities to fluoroquinolones, corresponding to those with
      single mutations. This increase in the incidence of strains with a single
      mutation in the gyrA gene portends a further increase in the incidence of strains
      with clinically significant resistance to fluoroquinolones.

PMID- 9276410
TI  - Rapid flow cytometric susceptibility testing of Candida albicans.
AB  - A rapid flow cytometric assay for in vitro antifungal drug susceptibility testing
      was developed by adapting the proposed reference method for broth macrodilution
      testing of yeasts. Membrane permeability changes caused by the antifungal agent
      were measured by flow cytometry using propidium iodide, a nucleic acid-binding
      fluorochrome largely excluded by the intact cell membrane. We determined the in
      vitro susceptibility of 31 Candida albicans isolates and two quality control
      strains (Candida parapsilosis ATCC 22019 and Candida krusei ATCC 6258) to
      amphotericin B and fluconazole. Amphotericin B MICs ranged from 0.03 to 2.0
      microg/ml, while fluconazole MICs ranged from 0.125 to 128 microg/ml. This method
      results in clear-cut endpoints that were reproducible. Four-hour incubation was
      required for fluconazole, whereas a 2-h incubation was sufficient for
      amphotericin B to provide MICs comparable to the reference macrodilution method
      developed by the National Committee for Clinical Laboratory Standards
      Subcommittee on Antifungal Susceptibility Tests. Results of these studies show
      that flow cytometry provides a rapid and sensitive in vitro method for antifungal
      susceptibility testing of C. albicans.

PMID- 9276412
TI  - Evaluation of performance of the RIBA processor system for automated analysis of
      the strip immunoblot assay for detection of antibodies to hepatitis C virus.
AB  - The performance of a new automated analyzer for the processing and interpretation
      of the RIBA Strip Immunoblot Assay (SIA), used in the diagnosis of hepatitis C
      virus (HCV) infection, was evaluated. Laboratory performance of the RIBA SIA was
      compared with that of two manually processed supplementary anti-HCV tests (RIBA
      HCV 3.0 SIA and INNO-LIA HCV Antibody III). Specificity of the automated
      processing of SIA was 100% for 90 selected anti-HCV-negative samples. On the
      other hand, 119 of 120 (99.2%) previously confirmed anti-HCV-positive samples
      were also positive when assayed on the automated processor. Results for all
      specimens except one (51 of 52) were concordant for manual and automated RIBA,
      while 15 of 68 sera tested with automated RIBA and the INNO-LIA assay showed
      different patterns of reactivity. Three HCV sensitivity panels and one
      seroconversion panel were also compared. The results show a high sensitivity for
      SIA NS3- and NS5-encoded antigens. Moreover, data obtained for the anti-HCV
      seroconversion panel and for samples with borderline or discordant anti-HCV
      enzyme-linked immunosorbent assay results suggest that bands with a relative
      intensity of >0.5 on the automated analyzer (theoretically negative) should be
      evaluated with care. Coefficients of variability ranged from 9 to 14.8% in an
      interassay reproducibility study. Overall, the performance of the automated
      analysis of SIA is comparable to that of the manual RIBA assay. The new automated
      processor for SIA bands proved to be sensitive and specific. Its use makes the
      optical scoring of bands unnecessary by indicating relative intensity values,
      which could be particularly useful in the follow-up care of anti-HCV-positive
      patients receiving antiviral therapy.

PMID- 9276411
TI  - Detection of vancomycin-resistant enterococci in fecal samples by PCR.
AB  - Surveillance cultures for vancomycin-resistant enterococci (VRE) are time
      consuming and expensive for the laboratory to perform. Therefore, we investigated
      the use of PCR as an alternative method of detecting and identifying VRE directly
      in fecal samples. PCR primers directed to vanA, vanB, vanC1, vanC2, and
      enterococcal ligase genes were used to detect and identify VRE in fecal material
      obtained by rectal or perirectal swabbing. Although PCR-inhibitory substances
      were present in DNA prepared directly from the swabs, the inhibitory substances
      could be reduced by processing the nucleic acid with two commercially available
      DNA preparation columns. Fecal material from 333 swabs was cultured on several
      selective agar media before and after broth enrichment. DNA was extracted from
      the fecal material and was analyzed by PCR. By using all four primer sets, only
      59 (67.8%) of the samples were positive for vanA. However, after retesting the
      negative samples with only the vanA primer set, 77 (88.5%) of 87 specimens that
      were culture positive for Enterococcus faecium containing vanA were positive by
      PCR. One specimen was PCR positive for the vanA gene but culture negative for
      enterococci. The specificity of the vanA assay was 99.6%. PCR analysis of
      enrichment broth samples with all four primers sets after 15 to 18 h of
      incubation detected 74 (85.1%) of the 87 culture-positive specimens. The
      specificity of the vanA assay after the enrichment step was 100%. No vanB
      containing enterococci were recovered by culture. Since 16 samples can be tested
      by PCR in 4 h (including electrophoresis), identification of VRE is possible
      within 8 h of specimen submission at a cost of approximately $10.12/assay. Thus,
      PCR may be a cost-effective alternative to culture for surveillance of VRE in
      some hospitals.

PMID- 9276413
TI  - Identification of clinically relevant viridans group streptococci to the species
      level by PCR.
AB  - A PCR assay that allows identification of clinically relevant viridans group
      streptococci (Streptococcus gordonii, S. mitis, S. mutans, S. oralis, S.
      salivarius, and S. sanguis) to the species level and identification of milleri
      group streptococci (S. anginosus, S. constellatus, and S. intermedius) to the
      group level was developed. This assay was based on specific amplification of
      internal fragments of genes encoding D-alanine:D-alanine ligases which are
      species specific and ubiquitous in prokaryotes possessing peptidoglycan. The
      specificity of this assay was tested on 9 reference strains and 91 characterized
      clinical isolates. This assay offers a specific and rapid alternative to
      phenotypic or DNA-DNA hybridization methods for identification of clinically
      relevant viridans group streptococci.

PMID- 9276414
TI  - Molecular epidemiology and antibiotic susceptibility of enterococci in
      Cincinnati, Ohio: a prospective citywide survey.
AB  - To determine patterns of antimicrobial susceptibility among enterococci and to
      assess molecular characteristics of vancomycin-resistant enterococci, 157
      clinical blood isolates of enterococci from 10 hospitals in Cincinnati, Ohio,
      were prospectively collected during a 6-month period from February to July 1995.
      The isolates included 108 (69%) E. faecalis isolates, 46 (29%) E. faecium
      isolates, and 1 isolate each of E. avium, E. durans, and E. gallinarum. The E.
      faecalis and E. faecium isolates differed in their susceptibilities to ampicillin
      (100 versus 20%), ampicillin-sulbactam (100 versus 13%), vancomycin (100 versus
      57%), imipenem (94 versus 2%), and high levels of gentamicin (59 versus 83%).
      Supplemental susceptibility testing of the 21 vancomycin-resistant isolates
      showed that 21 (100%) were susceptible to chloramphenicol and that only 7 (33%)
      were susceptible to doxycycline. Nineteen (90%) of the vancomycin-resistant E.
      faecium isolates were of the VanB phenotype, with vanB resistance genes detected
      by PCR and hybridization with gene-specific probes; and the E. gallinarum
      isolates demonstrated the VanC phenotype with the vanC1 gene. One vancomycin
      resistant E. faecium isolate was highly resistant to both teicoplanin and
      vancomycin, corresponding to the VanA phenotype; however, it was found to have
      the vanB gene. Pulsed-field gel electrophoresis (PFGE) revealed that all of the
      19 E. faecium isolates with the VanB phenotype had identical to closely related
      banding patterns. Hybridization of restriction enzyme-digested DNA separated by
      PFGE with a vanB gene probe demonstrated differences in the locations of vanB
      genes that corresponded closely to the PFGE banding patterns. Our study has
      documented that the emerging vancomycin resistance in our city was mainly due to
      the clonal dissemination of a single strain of E. faecium VanB.

PMID- 9276416
TI  - Culturing selects for specific genotypes of Borrelia burgdorferi in an enzootic
      cycle in Colorado.
AB  - In Colorado, Borrelia burgdorferi sensu stricto, the etiologic agent of Lyme
      disease, is maintained in an enzootic cycle between Ixodes spinipalpis ticks and
      Neotoma mexicana rats (27). The frequencies of flagellin (fla), 66-kDa protein
      (p66), and outer surface protein A (ospA) alleles were examined in 71 B.
      burgdorferi isolates from samples from Colorado. Approximately two-thirds of
      these samples were isolates from I. spinipalpis ticks that had been cultured in
      BSK-H medium prior to DNA extraction. The remaining samples were from total DNA
      extracted directly from infected I. spinipalpis ticks. A portion of each gene was
      amplified by PCR and screened for genetic variability by single-strand
      conformation polymorphism (SSCP) analysis. We identified three alleles in the fla
      gene, seven in the p66 gene, and seven in the ospA gene. Sequencing verified that
      the amplified products originated from B. burgdorferi template DNA and indicated
      100% sensitivity and specificity of the SSCP analysis. The frequencies of the p66
      and ospA alleles were significantly different between cultured and uncultured
      spirochetes. The number of three-locus genotypes and the genetic diversity of
      alleles at all loci were consistently lower in cultured spirochetes, suggesting
      that culturing of B. burgdorferi in BSK-H medium may select for specific
      genotypes.

PMID- 9276415
TI  - Parity among the randomly amplified polymorphic DNA method, multilocus enzyme
      electrophoresis, and Southern blot hybridization with the moderately repetitive
      DNA probe Ca3 for fingerprinting Candida albicans.
AB  - Randomly amplified polymorphic DNA (RAPD) analysis, multilocus enzyme
      electrophoresis (MLEE), and Southern blot hybridization with moderately
      repetitive DNA probes have emerged as effective fingerprinting methods for the
      infectious fungus Candida albicans. The three methods have been compared for
      their capacities to identify identical or highly related isolates, to cluster
      weakly related isolates, to discriminate between unrelated isolates, and to
      assess microevolution within a strain. By computing similarity coefficients
      between 29 isolates from three cities within the continental United States,
      strong concordance of the results is demonstrated for RAPD analysis, MLEE, and
      Southern blot hybridization with the moderately repetitive probe Ca3, and weaker
      concordance of the results is demonstrated for these three fingerprinting methods
      and Southern blot hybridization with the moderately repetitive probe CARE2. All
      methods were also demonstrated to be able to resolve microevolution within a
      strain, with the Ca3 probe exhibiting the greatest resolving power. The strong
      correlations demonstrated between polymorphic markers assessed by the four
      independent fingerprinting methods and the nonrandom association between loci
      demonstrated by RAPD analysis and MLEE provide evidence for strong linkage
      disequilibrium and a clonal population structure for C. albicans. In addition, a
      synapomorphic allele, Pep-3A, was found to be present in all members of one of
      the three clusters discriminated by RAPD analysis, MLEE, and Ca3 fingerprinting,
      supporting the concordance of the clustering capacities of the three methods, the
      robustness of the clusters, and the clonal nature of the clusters.

PMID- 9276417
TI  - Identification of clinical isolates of indole-positive Klebsiella spp., including
      Klebsiella planticola, and a genetic and molecular analysis of their beta
      lactamases.
AB  - In a collection of 43 indole-positive Klebsiella clinical isolates, which were
      initially identified as Klebsiella oxytoca, there were 18 isolates which
      exhibited a pattern characteristic of extended-spectrum beta-lactamase (ESBL)
      resistance. This study aimed to confirm their identity by biochemical tests and
      by PCR and to determine the genetic basis for their resistance to the beta
      lactams and broad-spectrum cephalosporins. Chromosomal beta-lactamase genes were
      analyzed by PCR, and plasmid-mediated beta-lactamase genes were analyzed by
      conjugation and transformation. There were 39 isolates which grew on melezitose
      but failed to grow on 3-hydroxybutyrate, confirming them as K. oxytoca. PCR
      analysis of their beta-lactamase genes divided these isolates into two groups,
      the bla(OXY-1) group and the bla(OXY-2) group. Each group had beta-lactamases
      with different isoelectric points; the bla(OXY-1) group had beta-lactamases with
      isoelectric points at 7.2, 7.8, 8.2, and 8.8, and the more common bla(OXY-2)
      group had beta-lactamases with pIs at 5.2, 5.4 (TEM-1), 5.7, 5.9, 6.4, and 6.8. A
      pI of 5.2 was the most frequently detected and accounted for 59% of all the
      bla(OXY-2) beta-lactamases. Hyperproduction of clavulanate-inhibited chromosomal
      beta-lactamases was detected in 17 K. oxytoca isolates, resulting in an ESBL
      phenotype. K. oxytoca isolates having a plasmid-mediated genetic basis for their
      ESBL phenotype were not found, confirming that, in K. oxytoca, plasmids are
      rarely involved in conferring resistance to the newer cephalosporins. Four
      isolates proved to be isolates of K. planticola in which the beta-lactamase genes
      failed to react with the primers used in the PCR. One K. planticola isolate
      contained a transferable plasmid harboring the SHV-5 beta-lactamase gene and
      showed an ESBL phenotype, while the other non-ESBL K. planticola isolates
      contained chromosomal beta-lactamases with isoelectric points at 7.2, 7.7, and
      7.9 plus 7.2.

PMID- 9276418
TI  - Identification of a Klebsiella pneumoniae strain associated with nosocomial
      urinary tract infection.
AB  - To differentiate between relapse of infection and reinfection of the urinary
      tract due to Klebsiella pneumoniae, 33 K. pneumoniae isolates collected from 20
      patients with spinal cord injury (SCI) over 2 years were typed by genomic
      fingerprinting by repetitive-element PCR. Clinical isolates obtained from the
      same patients with recurrent episodes of urinary tract infection (UTI) revealed
      identical genomic fingerprints indicating relapse of UTI due to K. pneumoniae,
      despite appropriate antibiotic therapy. Seventeen isolates obtained from 8 of the
      20 SCI patients shared a common genotype, termed RD6. Among non-SCI patients
      residing in other nursing units, the RD6 genotype was found in 5 of 10 patients
      with K. pneumoniae UTI but in only 1 of 20 patients with K. pneumoniae infection
      that did not involve the urinary tract, suggesting a strong association of this
      genotype with UTI. All RD6 isolates exhibited strong adherence (> or =50 adherent
      bacteria per cell) to HEp-2 cells, whereas other K. pneumoniae isolates generally
      did not adhere to or adhered very weakly to HEp-2 cells (< or =5 adherent
      bacteria per cell). Adherence was inhibited either by 4% D-mannose or by anti
      type 1 fimbrial rabbit serum. These results suggest that the capacity of K.
      pneumoniae RD6 isolates to cause UTI may be mediated by its striking adherence to
      mammalian cells.

PMID- 9276419
TI  - PCR-enzyme-linked immunosorbent assay and partial rRNA gene sequencing: a
      rational approach to identifying mycobacteria.
AB  - A PCR-enzyme-linked immunosorbent assay (ELISA) for amplification and rapid
      identification of mycobacterial DNA coding for 16S rRNA was developed. The PCR
      selectively targeted and amplified part of the 16S rRNA gene from all
      mycobacteria while simultaneously labelling one strand of the amplified product
      with a 5' fluorescein-labelled primer. The identity of the labelled strand was
      subsequently determined by hybridization to a panel of mycobacterial species
      specific capture probes, which were immobilized via their 5' biotin ends to a
      streptavidin-coated microtiter plate. Specific hybridization of a 5' fluorescein
      labelled strand to a species probe was detected colorimetrically with an anti
      fluorescein enzyme conjugate. The assay was able to identify 10 Mycobacterium
      spp. A probe able to hybridize to all Mycobacterium species (All1) was also
      included. By a heminested PCR, the assay was sensitive enough to detect as little
      as 10 fg of DNA, which is equivalent to approximately three bacilli. The assay
      was able to detect and identify mycobacteria directly from sputa. The
      specificities of the capture probes were assessed by analysis of 60 mycobacterial
      strains corresponding to 18 species. Probes Avi1, Int1, Kan1, Xen1, Che1, For1,
      Mal1, Ter1, and Gor1 were specific. The probe Tbc1 cross-hybridized with the
      Mycobacterium terrae amplicon. Analysis of 35 strains tested blind resulted in 34
      strains being correctly identified. This method could be used for rapid
      identification of early cultures and may be suitable for the detection and
      concurrent identification of mycobacteria within clinical specimens.

PMID- 9276421
TI  - Evidence for recombination in the flagellin locus of Campylobacter jejuni:
      implications for the flagellin gene typing scheme.
AB  - The flagellin subunit of the flagellar filament in Campylobacter jejuni is
      encoded by two highly homologous tandem genes, flaA and flaB. The flaA gene was
      sequenced in 18 strains of C. jejuni, including isolates from three outbreak
      groups. Sequences obtained were compared with flaA sequences available in the
      GenBank database, and all were analyzed for mosaic gene structure by using
      recently described statistical tests for detecting gene conversion among aligned
      sets of sequences. Strong evidence was found supporting recombination between
      flaA genes of different strains (i.e., intergenomic recombination). Intragenomic
      recombination between the flaA and flaB genes of C. jejuni TGH9011 was also
      demonstrated. Both mechanisms of recombination may act as a potential means by
      which pathogenic strains can generate increased antigenic diversity, so allowing
      them to escape the immunological responses of the host. Furthermore,
      demonstration of recombination within and between flagellin loci of natural
      strains suggests that flagellin gene typing (restriction fragment length
      polymorphism analysis of PCR-amplified flagellin genes) cannot be considered a
      stable method for long-term monitoring of pathogenic Campylobacter populations.

PMID- 9276420
TI  - Study of Norwalk virus and Mexico virus infections at Ga-Rankuwa Hospital, Ga
      Rankuwa, South Africa.
AB  - Small round-structured viruses (SRSVs) or Norwalk-like viruses have been
      implicated as an important causative agent of gastroenteritis outbreaks. We used
      the relatively newly developed recombinant enzyme immunoassays (EIAs) to
      determine the seroprevalence of Norwalk virus (NV) and Mexico virus (MxV) in a
      family-based cohort and an antenatal clinic cohort at Ga-Rankuwa Hospital, Ga
      Rankuwa, South Africa. High prevalences (96 to 99%) of anti-NV and anti-MxV
      antibodies were detected in both cohorts. We also investigated the pattern of
      antibody acquisition in a cohort of infants and young children without
      gastroenteritis and found that by 48 months of age all children had acquired
      adult antibody levels to both these viruses. Lastly, we tested 276 stool
      specimens collected from infants and young children with gastroenteritis for the
      presence of NV or MxV antigen by recombinant EIAs to each virus, by electron
      microscopy (EM), and by reverse transcription (RT)-PCR. NV and MxV antigens were
      present in 1.8 and 4.3% of the stool specimens, respectively, by the recombinant
      EIAs; 9.2% were positive for SRSVs by EM, and 25% of these SRSVs gave a positive
      result by RT-PCR for primer pair 35-36 directed to a region of the RNA-dependent
      RNA polymerase gene. The seroprevalence studies indicate a high level of exposure
      to these viruses in both children and adults. Although the viral antigens are not
      highly prevalent in diarrheal stools, it was determined by the two assays for NV
      and MxV that children are, nevertheless, infected early in life.

PMID- 9276422
TI  - DNA fingerprinting of Mycobacterium tuberculosis strains from patients with
      pulmonary tuberculosis in Honduras.
AB  - Mycobacterium tuberculosis isolates from 84 patients with pulmonary tuberculosis
      in Honduras were characterized by restriction fragment length polymorphism
      analysis. Seventy-three different IS6110 patterns were found; 63 of these were
      unique and 10 were shared by two to three strains each. Thus, no ongoing spread
      of any specific clone of bacteria could be demonstrated.

PMID- 9276423
TI  - Simultaneous identification of campylobacters and prediction of quinolone
      resistance by comparative sequence analysis.
AB  - Comparative sequence analysis of a 30-bp segment in the quinolone resistance
      determining region of campylobacters not only allows for the detection of base
      changes associated with resistance but also is a powerful tool for species
      identification based on silent mutations.

PMID- 9276424
TI  - A molecular scheme based on 23S rRNA gene polymorphisms for rapid identification
      of Campylobacter and Arcobacter species.
AB  - 23S rRNA gene PCR amplicons from 118 strains representing 15 species of
      Campylobacter and four species of Arcobacter were consecutively digested with
      HpaII, CfoI, and HinfI. A reproducible and discriminatory identification scheme
      based on combined restriction patterns was developed by using reference strains
      and was applied to the identification of a variety of isolates.

PMID- 9276426
TI  - Tampon sampling for diagnosis of bacterial vaginosis: a potentially useful way to
      detect genital infections?
AB  - Genital tract infections are important causes of ill health in developing
      countries, but diagnosis is difficult. Bacterial vaginosis (BV) was correctly
      diagnosed by using a vaginal specimen obtained by tampon sampling in 22 of 24
      women (91.6%) for whom BV was diagnosed by Gram staining. The yield for other
      vaginal infections was higher (28% for Trichomonas vaginalis and 32.7% for
      Candida albicans) than it was for cervical infections (0% for Neisseria
      gonorrhoeae and 30% for Chlamydia trachomatis). Tampon sampling was acceptable to
      patients and may facilitate diagnosis of genital infections in developing
      countries.

PMID- 9276425
TI  - Comparison of use of enzyme-linked immunosorbent assay-based kits and PCR
      amplification of rRNA genes for simultaneous detection of Entamoeba histolytica
      and E. dispar.
AB  - A comparison of the use of three commercially available enzyme-linked
      immunosorbent assay-based kits and PCR amplification of rRNA genes to detect and
      differentiate Entamoeba histolytica from E. dispar was carried out. Only the
      Techlab kit did not cross-react with E. dispar antigens, but it was 100 times
      less sensitive than PCR in detection of and differentiation between the two types
      of Entamoeba.

PMID- 9276427
TI  - Use of the isolator 1.5 microbial tube for culture of synovial fluid from
      patients with septic arthritis.
AB  - Synovial fluid specimens obtained from patients with arthritis were plated onto
      solid media (conventional cultures) or inoculated into an Isolator 1.5 microbial
      tube (Isolator cultures), and the yield and time to detection of organisms were
      compared. Overall, 144 specimens obtained from 137 patients were processed, and
      31 (21.5%) cultures obtained from 29 patients were positive by at least one
      method. Staphylococcus aureus was isolated from 12 patients, Streptococcus
      pneumoniae and Kingella kingae were isolated from 4 patients each, group G
      streptococci were isolated from 3 patients, Staphylococcus epidermidis and
      members of the family Enterobacteriaceae were isolated from 2 patients each, and
      Streptococcus mitis and Peptostreptococcus prevotii were isolated from 1 patient
      each. Overall, the causative organism was detected in 31 of 31 (100.0%) Isolator
      cultures and 24 of 31 (77.4%) conventional cultures (P < 0.02). Twenty-nine of 31
      (93.5%) positive Isolator cultures and 20 of 24 (83.3%) conventional cultures
      were positive by the second day of incubation. Among the 24 cultures positive by
      both methods, higher numbers of CFU per milliliter were detected with the
      Isolator system in 13 cultures and with conventional cultures in 2 cultures (P <
      0.002). Inoculation of synovial fluid into an Isolator 1.5 microbial tube
      improves the recovery of organisms causing septic arthritis.

PMID- 9276428
TI  - Stabilities of free and complexed human immunodeficiency virus p24 antigens
      during short- and long-term storage.
AB  - By the standard p24 assay there was a 25 to 27% decrease in free p24 antigen in
      serum after storage at 4 degrees C over 14 days but no loss at -70 degrees C.
      There was no loss at either temperature by the immune complex dissociation (ICD)
      procedure. Furthermore, there was no significant loss of detectable p24 in serum
      by either the ICD or the standard p24 assay after 700 days of storage at -70
      degrees C.

PMID- 9276429
TI  - Diagnosis of brucellosis by using blood cultures.
AB  - The performances of three blood culture systems, Hemoline performance diphasic
      medium (bioMerieux, Marcy l'Etoile, France), Bactec Plus Aerobic/F* (Becton
      Dickinson, Paramus, N.J.), and Vital Aer (bioMerieux), were compared for the
      diagnosis of 17 cases of brucellosis. By using a 5-day incubation protocol,
      positive results were 52.9, 82.4, and 11.8%, respectively. When the protocol was
      extended to 7 days, the results were 76.5, 94.1, and 47.1%, respectively. Bactec
      was the fastest system (P < 0.05).

PMID- 9276431
TI  - Wooden sticks as the source of a pseudoepidemic of infection with Rhizopus
      microsporus var. rhizopodiformis among immunocompromised patients.
AB  - Wooden sticks used to suspend feces obtained for surveillance cultures were found
      to be the source of Rhizopus microsporus var. rhizopodiformis causing a pseudo
      outbreak among 17 immunocompromised patients cared for in three different wards.
      Nonsterile wooden products should therefore not be used for collecting, handling,
      and processing specimens for microbiological examination.

PMID- 9276430
TI  - Subtyping of human immunodeficiency virus type 1 strains by using antibodies
      specific for the third variable domain (V3) of gp120: results may be affected by
      divergent V3 sequences.
AB  - Human immunodeficiency virus type 1 serotype C was found in 545 of 712 Ethiopian
      patients by peptide enzyme immunoassay. Serotyping failed in 146 samples due to
      the absence of V3 antibodies or multiple reactivities. In 6 of 34 samples,
      discordant results were obtained by serotyping and genotyping, possibly due to
      divergent V3 sequences.

PMID- 9276432
TI  - Evaluation of a commercial ligase chain reaction kit (Abbott LCx) for direct
      detection of Mycobacterium tuberculosis in pulmonary and extrapulmonary
      specimens.
AB  - Direct detection of Mycobacterium tuberculosis by means of a commercial ligase
      chain reaction DNA amplification method (LCx M. tuberculosis; Abbott Diagnostics
      Division, Abbott Park, Ill.) was investigated with 511 (including 147
      extrarespiratory) specimens collected from 358 patients. LCx results were
      compared with standard microbiological data, and conflicting cases were resolved
      according to the final clinical diagnosis. M. tuberculosis was detected in 45 of
      358 subjects by means of the LCx test. The test was negative for all 30 specimens
      with mycobacteria other than M. tuberculosis. The sensitivity, specificity, and
      positive and negative predictive values for the LCx test, compared with culture
      results, were 93.90, 92.31, 70.00, and 98.75%, respectively; these values rose in
      resolved cases to 95.53, 99.25, 97.27, and 98.75%, respectively. With respiratory
      specimens, for which the LCx system is licensed, the sensitivity reached 98.97%.
      In patients with a final clinical diagnosis of tuberculosis the sensitivity of
      the LCx system was 89.36% compared to 82.98% for cultures and 78.72% for
      microscopy. We conclude that the LCx test is user friendly, rapid, fairly
      sensitive, and highly specific. It can also be effectively used on extrapulmonary
      specimens provided possible false-negative results are taken into account.
      However, the use of LCx test appears to be less appropriate for the monitoring of
      antituberculosis therapy, as the majority of samples from treated tuberculosis
      patients gave consistently positive results, despite the sterilization of
      cultures.

PMID- 9276433
TI  - Use of a single swab in multi-microbe or flex trans transport medium for
      detection of Chlamydia trachomatis by Roche Amplicor PCR and culture in specimens
      from two different patient populations.
AB  - The Roche Amplicor PCR increased the detection of Chlamydia trachomatis compared
      with culture in promptly processed clinical specimens from a local clinic (100
      and 86.5%, respectively) and in samples with delayed processing transported from
      distant facilities (100 and 72.7%, respectively). A single swab collected in
      culture transport medium was used. Two media, Multi-Microbe and Flex Trans, were
      tested and found to be equally acceptable.

PMID- 9276434
TI  - A new experimental in vitro culture medium for cultivation of Leishmania species.
AB  - A new liquid culture medium prepared with chemicals that can be obtained
      economically and commercially was tested in in vitro cultivation of Leishmania
      promastigotes to obtain a large number of organisms to use in serological
      studies. The number of Leishmania infantum and Leishmania tropica promastigotes
      taken from Novy-MacNeal-Nicolle (NNN) medium reached 1 x 10(7)/ml at the end of
      the 8th day in our new medium, though in NNN medium the number of organisms
      reached only 5 x 10(6)/ml. After 10 subsequent passages, the culture medium
      prepared was evaluated as being quite inexpensive, simple, and successful
      compared with other commercially available liquid culture media.

PMID- 9276435
TI  - Epidemiological interpretation of chromosomal macro-restriction fragment patterns
      analyzed by pulsed-field gel electrophoresis.

PMID- 9276436
TI  - Proton pumping by cytochrome c oxidase is coupled to peroxidase half of its
      catalytic cycle.
AB  - The four-electron reaction cycle of cytochrome oxidase is comprised of an eu
      oxidase phase in which the enzyme receives the first two electrons and reduces
      oxygen to bound peroxide and a peroxidase phase in which the peroxy state formed
      in the eu-oxidase half of the cycle is reduced by the 3rd and 4th electrons to
      the ferryl-oxo state and oxidized form, respectively. Here we show that the
      ferrocyanide-peroxidase activity of cytochrome c oxidase incorporated in
      phospholipid vesicles is coupled to proton pumping. The H+/e- ratio for the
      ferrocyanide-peroxidase partial reaction is twice higher than for the overall
      ferrocyanide-oxidase activity and is close to 2. These results show that proton
      pumping by COX is confined to the peroxidase part of the enzyme catalytic cycle
      (transfer of the 3rd and 4th electron) whereas the eu-oxidase part (transfer of
      the first two electrons) may not be proton pumping.

PMID- 9276437
TI  - Submitochondrial distributions and stabilities of subunits 4, 5, and 6 of yeast
      cytochrome oxidase in assembly defective mutants.
AB  - The concentration and submitochondrial distribution of the subunit polypeptides
      of cytochrome oxidase have been studied in wild type yeast and in different
      mutants impaired in assembly of this respiratory complex. All the subunit
      polypeptides of the enzyme are associated with mitochondrial membranes of wild
      type cells, except for a small fraction of subunits 4 and 6 that is recovered in
      the soluble protein fraction of mitochondria. Cytochrome oxidase mutants
      consistently display a severe reduction in the steady-state concentration of
      subunit 1 due to its increased turnover. As a consequence, most of subunit 4,
      which normally is associated with subunit 1, is found in the soluble fraction. A
      similar shift from membrane-bound to soluble subunit 6 is seen in mutants blocked
      in expression of subunit 5a. In contrast, null mutations in COX6 coding for
      subunit 6 promote loss of subunit 5a. The absence of subunit 5a in the cox6
      mutant is the result of proteolytic degradation rather than regulation of its
      expression by subunit 6. The possible role of the ATP-dependent proteases Rca1p
      and Afg3p in proteolysis of subunits 1 and 5a has been assessed in strains with
      combined mutations in COX6, RCA1, and/or AFG3. Immunochemical assays indicate
      that another protease(s) must be responsible for most of the proteolytic loss of
      these proteins.

PMID- 9276438
TI  - PP2C gamma: a human protein phosphatase with a unique acidic domain.
AB  - We have cloned a novel cDNA from human skeletal muscle which encodes a protein
      phosphatase with a unique acidic domain. It is 34% identical to mammalian PP2C
      alpha and PP2C beta and we call it PP2C gamma. It more closely resembles PP2Cs
      from Paramecium tetraurelia and Schizosaccharomyces pombe than mammalian PP2Cs.
      Northern blot analysis shows that PP2C gamma is widely expressed, and is most
      abundant in testis, skeletal muscle, and heart. Like known PP2Cs, recombinant
      PP2C gamma requires Mg2+ or Mn2+ for activity. Unlike any other known
      phosphatase, PP2C gamma has a highly acidic domain: 75% of the 54 residues are
      glutamate or aspartate.

PMID- 9276439
TI  - Pervanadate elicits proliferation and mediates activation of mitogen-activated
      protein (MAP) kinase in the nucleus.
AB  - There is growing evidence for the role of protein tyrosine phosphatases in
      controlling such fundamental cellular processes as growth and differentiation.
      Pervanadate is a potent inhibitor of protein tyrosine phosphatase which has been
      observed here to induce proliferation in C3H10T1/2 mouse fibroblasts. Pervanadate
      also translocated/activated p42/44 mitogen-activated protein (MAP) kinase to the
      cell nucleus. An almost similar pattern of nuclear p42/44 MAP kinase stimulation
      is seen with TPA. On the other hand, TPA treatment results in a rapid activation
      of cytosolic MAP kinase which declines with time. Thus pervanadate appears as a
      very useful tool for studying tyrosine phosphorylation.

PMID- 9276440
TI  - A simple method for determining kinetic constants of complexing inactivation at
      identical enzyme and inhibitor concentrations.
AB  - The kinetics of complexing inactivation at identical enzyme and inhibitor
      concentrations were analyzed and the equations of product generation were derived
      when the free enzyme concentration is great, larger or smaller than the
      dissociation constant of inhibitor, K(I). The kinetic constants can be obtained
      by fitting the derived equations to the progress curve. Numerical examples show
      that this method is valid and gives satisfactory results.

PMID- 9276441
TI  - Prion proteins: evolution and preservation of secondary structure.
AB  - Prions cause a variety of neurodegenerative disorders that seem to result from a
      conformational change in the prion protein (PrP). Thirty-two PrP sequences have
      been subjected to phylogenetic analysis followed by reconstruction of the most
      probable evolutionary spectrum of amino acid replacements. The replacement rates
      suggest that the protein does not seem to be very conservative, but in the course
      of evolution amino acids have only been substituted within the elements of the
      secondary structure by those with very similar physico-chemical properties.
      Analysis of the full spectrum of single-step amino acid substitutions in human
      PrP using secondary structure prediction algorithms shows an over-representation
      of substitutions that tend to destabilize alpha-helices.

PMID- 9276442
TI  - Modulation of rat brain calpastatin efficiency by post-translational
      modifications.
AB  - Calpains, the thiol proteinases of the calcium-dependent proteolytic system, are
      regulated by a natural inhibitor, calpastatin, which is present in brain tissue
      in two forms. Although both calpastatins are highly active on human erythrocyte
      calpain, only one form shows a high inhibitory efficiency with both rat brain
      calpain isozymes. The second calpastatin form is almost completely inactive
      against homologous proteinases and can be converted into an active one by
      exposure to a phosphoprotein phosphatase, also isolated from rat brain.
      Phosphorylation of the active calpastatin by protein kinase C and protein kinase
      A promotes a decrease in its inhibitory efficiency. The interconversion between
      the two inhibitor forms seems involved in the adjustment of the level of
      intracellular calpastatin activity on specific cell requirements.

PMID- 9276443
TI  - Cytochrome P450IA2 and aromatic L-amino acid decarboxylase are hepatic
      autoantigens in autoimmune polyendocrine syndrome type I.
AB  - Autoimmune chronic active hepatitis (AI-CAH) is a feared component of autoimmune
      polyendocrine syndrome type I (APS I). In this study, immunoreactivity was
      assessed in sera from eight APS I patients, of whom three had AI-CAH, in an
      attempt to identify hepatic autoantigens. We performed indirect
      immunofluorescence staining of human and rat liver sections, Western blots on
      subcellular fractions of human and rat liver, immunoprecipitations of labelled
      aromatic L-amino acid decarboxylase (AADC) and cytochrome P450IA2 (CYP IA2)
      expressed by an in vitro transcription and translation system and studies of
      enzymatic activity. Autoantibodies against AADC were present in sera from all
      eight APS I patients, while immunoreactivity against CYP IA2 was only found in
      sera from the three APS I patients with AI-CAH. Enzymatic activity of CYP IA2 was
      inhibited by sera from APS I patients with AI-CAH but not by control sera. Our
      results show that CYP IA2 and AADC constitute hepatic autoantigens in patients
      with APS I and that immunoreactivity against CYP IA2 is associated with the
      presence of AI-CAH.

PMID- 9276444
TI  - The Arabidopsis Cks1At protein binds the cyclin-dependent kinases Cdc2aAt and
      Cdc2bAt.
AB  - In Arabidopsis, two cyclin-dependent kinases (CDK), Cdc2aAt and Cdc2bAt, have
      been described. Here, we have used the yeast two-hybrid system to identify
      Arabidopsis proteins interacting with Cdc2aAt. Three different clones were
      isolated, one of which encodes a Suc1/Cks1 homologue. The functionality of the
      Arabidopsis Suc1/Cks1 homologue, designed Cks1At, was demonstrated by its ability
      to rescue the temperature-sensitive cdc2-L7 strain of fission yeast at low and
      intermediate expression levels. In contrast, high cks1At expression levels
      inhibited cell division in both mutant and wild-type yeast strains. Cks1At binds
      both Cdc2aAt and Cdc2bAt in vivo and in vitro. Furthermore, we demonstrate that
      the fission yeast Suc1 binds Cdc2aAt but only weakly Cdc2bAt, whereas the human
      CksHs1 associated exclusively with Cdc2aAt.

PMID- 9276445
TI  - Differential expression of mRNAs for endopeptidases in phenotypically modulated
      ('dedifferentiated') human articular chondrocytes.
AB  - Human articular chondrocytes modulated away from their original phenotype by
      serial subcultures in monolayer differentially express mRNAs for endopeptidases.
      The mRNAs for the cathepsins B and L are extremely low in differentiated cells,
      but are soon expressed in parallel with the loss of the differentiated state. In
      contrast, the mRNA for collagenase-1 is strongly expressed by differentiated
      chondrocytes and declines rapidly following phenotypic modulation. The mRNA for
      stromelysin-1 and the tissue inhibitor of metalloproteinases-2 is high and does
      not appreciably change after modulation. Chondrocyte activation induced by
      alteration of its original phenotype leads to the expression of endopeptidases in
      a way that markedly differs from that induced by cytokines. The results are
      relevant to cartilage catabolism in osteoarthritis and suggest a prominent role
      of fibroblastic metaplasia on the part of the chondrocytes as a mechanism of
      expressing catabolic endopeptidases.

PMID- 9276446
TI  - Monoclonal antibodies neutralizing the toxin II from Androctonus australis hector
      scorpion venom: usefulness of a synthetic, non-toxic analog.
AB  - Scorpion venom contains toxins that act on ion channels. Some are responsible for
      the noxious effects observed when people are stung by scorpions. The study of the
      neutralization of these molecules and the production of monoclonal antibodies
      (mAbs) should prove valuable. Toxin II from Androctonus australis hector scorpion
      (AahII) is one of the most potent toxins and has been well-characterized and
      studied. Producing mAbs against such molecules is often difficult due to their
      toxicity. We used a synthetic, non-toxic analog, (Abu)8-AahII, to obtain mAbs
      which recognize and neutralize the native toxin AahII. Sets of peptides spanning
      the entire sequence of AahII were assayed to identify the binding sites of the
      mAbs. The various mAbs recognized only the largest peptides (12-17 residues).
      They recognized peptides corresponding to different parts of the AahII sequence,
      suggesting that several regions of the (Abu)8-AahII sequence mimic AahII epitopes
      and then elicit mAbs directed against toxin.

PMID- 9276447
TI  - 1,2-Diacylglycerol hydroperoxides induce the generation and release of superoxide
      anion from human polymorphonuclear leukocytes.
AB  - We examined the effect of 1-palmitoyl-2-linoleoylglycerol (PLG), PLG hydroxide
      (PLG-OH), and PLG hydroperoxide (PLG-OOH) on the release of superoxide anion from
      human PMNs monitored by the chemiluminescence generated by the superoxide anion
      sensitive reagent, 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1,2
      a]pyrazin++ +-3-one (MCLA). PLG-OOH at low micromolar concentrations stimulated
      human PMNs whereas PLG and PLG-OH did not. 1,3-Dilinoleoylglycerol hydroperoxide,
      1-palmitoyl-2-linoleoylphosphatidylcholine hydroperoxide, and linoleic acid
      hydroperoxide were much less efficient in stimulating human PMNs than PLG-OOH.
      The PKC inhibitors, chelerythrine chloride and staurosporine, inhibited the
      stimulation of PMNs. Possible pathophysiological role of 1,2-diacylglycerol
      hydroperoxides is discussed.

PMID- 9276449
TI  - Release of opioid peptides, gluten exorphins by the action of pancreatic
      elastase.
AB  - The release of opioid peptides, gluten exorphins A, which have been isolated from
      the pepsin-thermolysin digest of wheat gluten, with gastrointestinal proteases
      was examined. High levels of gluten exorphin A5 (Gly-Tyr-Tyr-Pro-Thr)
      immunoreactive materials were detected in the pepsin-pancreatic elastase digest
      by a competitive ELISA. From this digest, gluten exorphin A5, B5 and B4 were
      isolated. This means that these peptides are released in the gastrointestinal
      tracts after ingestion of wheat gluten. The yield of gluten exorphin A5 in the
      pepsin-elastase digest was larger than that in the pepsin-thermolysin digest. The
      gluten exorphin A5 sequence is found 15 times in the primary structure of the
      high molecular weight glutenin. The region from which gluten exorphin A5 was
      released by the action of pancreatic elastase was identified using synthetic
      fragment peptides.

PMID- 9276448
TI  - Molecular and functional characterization of a 5-HT4 receptor cloned from human
      atrium.
AB  - 5-Hydroxytryptamine (5-HT) has been shown to exert positive inotropic,
      chronotropic, and lusitropic effects and to stimulate the L-type calcium channel
      current (I(Ca)) in human atrial tissue through activation of the
      pharmacologically defined 5-HT4 receptor subtype. However, the molecular nature
      of the receptor(s) involved in these effects is still unknown. In the present
      study, we report the molecular nature of a 5-HT4 receptor cloned from human
      atrium, h5-HT4A. Sequence analysis reveals that h5-HT4A displays a 93% protein
      identity with the short form of the 5-HT4 receptor recently isolated from rat
      brain. h5-HT4A mRNA is expressed in human atrium but not ventricle, and is also
      found in brain and GI tract. h5-HT4A transiently expressed in COS-7 cells
      displays a classical 5-HT4 pharmacological profile. However, affinities of the h5
      HT4A receptor for agonists such as ML10302, BIMU1, renzapride or zacopride were 4
      10-fold lower than the ones found in brain. Moreover, the stimulatory patterns of
      cAMP formation by h5-HT4A in response to the 5-HT4 agonists ML10302 and
      renzapride were very similar to the patterns of stimulation of I(Ca) obtained in
      response to these compounds in human atrial myocytes. We conclude that h5-HT4A
      likely mediates the effects of 5-HT in human atrium and may differ from 5-HT4
      receptor isoforms present in the brain and GI tract.

PMID- 9276450
TI  - 9-cis-retinoic acid enhances fatty acid-induced expression of the liver fatty
      acid-binding protein gene.
AB  - The role of retinoic acids (RA) on liver fatty acid-binding protein (L-FABP)
      expression was investigated in the well differentiated FAO rat hepatoma cell
      line. 9-cis-Retinoic acid (9-cis-RA) specifically enhanced L-FABP mRNA levels in
      a time- and dose-dependent manner. The higher induction was found 6 h after
      addition of 10(-6) M 9-cis-RA in the medium. RA also enhanced further both L-FABP
      mRNA levels and cytosolic L-FABP protein content induced by oleic acid. The
      retinoid X receptor (RXR) and the peroxisome proliferator-activated receptor
      (PPAR), which are known to be activated, respectively, by 9-cis-RA and long chain
      fatty acid (LCFA), co-operated to bind specifically the peroxisome proliferator
      responsive element (PPRE) found upstream of the L-FABP gene. Our result suggest
      that the PPAR-RXR complex is the molecular target by which 9-cis-RA and LCFA
      regulate the L-FABP gene.

PMID- 9276451
TI  - Mechanism of gluconate synthesis in Rhizobium meliloti by using in vivo NMR.
AB  - The dehydrogenation of [1-(13)C]- and [2-(13)C]glucose into gluconate was
      monitored by NMR spectroscopy in living cell suspensions of two Rhizobium
      meliloti strains. The synthesis of gluconate was accompanied, in the cellular
      environment, by the formation of two gluconolactones, a gamma-lactone being
      detected in addition to the expected delta-lactone. These lactones--as well as
      the gluconate--could be further metabolized by the cells. The delta-lactone was
      utilized faster than the gamma-lactone. The presence--in significant amounts--and
      the relative stability of the lactones raise the question of their possible
      physiological significance.

PMID- 9276452
TI  - Temperature dependence of the electrogenic reaction in the QB site of the
      Rhodobacter sphaeroides photosynthetic reaction center: the QA-QB --> QAQB-
      transition.
AB  - The temperature dependencies for the kinetics and relative amplitudes of
      electrogenic reaction(s) coupled with the first reduction of the secondary
      quinone acceptor QB were measured with dark-adapted chromatophores of Rhodobacter
      sphaeroides. The kinetics, while acceptably fitted by a single exponent at room
      temperature, clearly split into two components below 15 degrees C (rise times, 25
      micros and 300 micros at pH 7.0 and 10 degrees C) with the slow phase ousting the
      fast one at pH > 9.0. The activation energies of the fast and slow phases were
      estimated at pH 7.0 as < 10 kJ/mol and 60-70 kJ/mol, respectively. To explain the
      kinetic heterogeneity of the QB --> QB- transition, we suggest two possible
      conformations for the neutral oxidized ubiquinone at the QB site: one with a
      hydrogen bond between the side chain carboxyl of Glu-L212 and the methoxy oxygen
      at C3 of the QB ring (QB-H-Glu centers) and the other one, without this bond
      (QB:Glu- centers). The fast phase is attributed to QA- QB-H-Glu --> QA QB-H-Glu
      transition, whereas the slow one to the QA- QB:Glu- --> QA- QB-H-Glu --> QA QB(-)
      H-Glu transition.

PMID- 9276453
TI  - mRNP3 and mRNP4 are phosphorylatable by casein kinase II in Xenopus oocytes, but
      phosphorylation does not modify RNA-binding affinity.
AB  - mRNP3 and mRNP4 (also called FRGY2) are two mRNA-binding proteins which are major
      constituents of the maternal RNA storage particles of Xenopus laevis oocytes. The
      phosphorylation of mRNP3-4 has been implicated in the regulation of mRNA masking.
      In this study, we have investigated their phosphorylation by casein kinase II and
      its consequence on their affinity for RNA. Comparison of the phosphopeptide map
      of mRNP3-4 phosphorylated in vivo with that obtained after phosphorylation in
      vitro by purified Xenopus laevis casein kinase II strongly suggests that casein
      kinase II is responsible for the in vivo phosphorylation of mRNP3-4 in oocytes.
      The phosphorylation occurs on a serine residue in a central domain of the
      proteins. The affinity of mRNP3-4 for RNA substrates remained unchanged after the
      treatment with casein kinase II or calf intestine phosphatase in vitro. This
      suggests that phosphorylation of these proteins does not regulate their
      interaction with RNA but rather controls their interactions with other proteins.

PMID- 9276454
TI  - The D13C variant of Bacillus schlegelii 7Fe ferredoxin is an 8Fe ferredoxin as
      revealed by 1H-NMR spectroscopy.
AB  - The N-terminal cluster binding motif Cys8XXXXXXXCys16....Cys49 of Bacillus
      schlegelii 7Fe ferredoxin, which provides the ligands to the [Fe3S4]+ cluster,
      was modified by the mutation Asp13 --> Cys. The mutant D13C is expressed in
      Escherichia coli as an 8Fe ferredoxin, with NMR properties similar to those of
      clostridial-type ferredoxins. The full assignment of the hyperfine shifted
      resonances indicates that Cys13 serves as ligand to the new fourth iron atom in
      the N-terminal cluster despite the atypical binding sequence
      CysXXXXCysXXCys....Cys. The C alpha-C beta-S-Fe dihedral angles of all cysteine
      ligands to the two [Fe4S4]2+ clusters of the D13C variant are similar to those
      observed in other 8Fe and 4Fe ferredoxins.

PMID- 9276455
TI  - Role of the distal hinge region of C1-inhibitor in the regulation of C1s
      activity.
AB  - A synthetic peptide corresponding to residues 448-459 of C1-inhibitor (C1-inh)
      binds to C1s, is a non-competitive inhibitor of C1s activity and prevents
      formation of an SDS-stable C1s-C1-inh complex. Substitutions of residues Q452,
      Q453 or F455 in this peptide resulted in loss of C1s binding and inhibitory
      activity of the peptide. NMR analysis of the peptide showed an area of well
      defined structure from E450 to F455. The side chains of Q452, Q453 and Q455 were
      exposed to the solvent and therefore available for C1s binding. The defined
      structure in the peptide is compatible with our computer model of the serpin
      domain of C1-inh.

PMID- 9276456
TI  - Nitric oxide synthase isoform III gene expression in rat liver is up-regulated by
      lipopolysaccharide and lipoteichoic acid.
AB  - This study was done to investigate the influence of Gram-negative and Gram
      positive sepsis on the expression of the three isoforms of nitric oxide synthase
      (NOS) gene in rat liver and kidney. Male Sprague-Dawley rats were treated with
      lipopolysaccharide (LPS, 10 mg/kg i.v.) as an in vivo model for Gram-negative
      sepsis or lipoteichoic acid (LTA, 10 mg/kg i.v.) as an in vivo model for Gram
      positive sepsis. Animals were killed 12 h and 24 h after i.v. treatment. NOS mRNA
      of the three isoforms was determined by RNase protection assay. NOS II gene
      expression was strongly induced after LPS or LTA treatment in rat liver and
      kidney, indicating the efficacy of this treatment to induce sepsis. We found no
      change of NOS I gene expression after LPS or LTA injection in rat liver and
      kidney. NOS III gene expression was increased about 8-fold 12 h and about 5-fold
      24 h after induction of sepsis in the rat liver whereas in the kidney there was
      no significant increase in NOS III gene expression. After correction for length
      NOS III mRNA was about 4- and 40-fold more abundant 12 h and 24 h after LPS
      treatment than NOS II mRNA in the liver, respectively. Twelve and 24 h after LTA
      treatment NOS III mRNA was about 18- and 140-fold more abundant than NOS II in
      the liver. These findings suggest that NOS III is an even more potent source of
      NO than NOS II in the liver after stimulation with LPS or LTA.

PMID- 9276457
TI  - Detection of specific IgE to human milk proteins in sera of atopic infants.
AB  - Specific IgE (sIgE) for cow's milk proteins (CMP) have been reported to be
      present in blood sera of exclusively breast-fed infants. The aim of this study
      was to find whether the presence of sIgE to human milk proteins in the sera of
      exclusively breast-fed infants could explain the apparent detection of sIgE to
      CMP in infants that were never previously in contact with cow's milk. sIgE for
      human milk whey proteins were found in the blood sera of atopic infants, and
      these sIgE strongly cross-reacted with the corresponding CMP. In none of the sera
      examined were sIgE to bovine beta-lactoglobulin detected.

PMID- 9276458
TI  - Protein splicing in the yeast Vma1 protozyme: evidence for an intramolecular
      reaction.
AB  - Protein splicing is an autocatalytic reaction of a single polypeptide in which a
      spliced intervening sequence is excised out and the two external regions are
      ligated with the peptide bond to yield two mature proteins. We examined the
      reaction mechanism using a folding-dependent in vitro protein splicing system.
      Protein splicing proceeds at an optimal pH of 7 and is an intramolecular
      reaction. The reaction is not inhibited by potential protease inhibitors,
      suggesting that its mechanism is different from those catalyzed by known
      proteases.

PMID- 9276459
TI  - Difference between PA700-like proteasome activator complex and the regulatory
      complex dissociated from the 26S proteasome implies the involvement of modulating
      factors in the 26S proteasome assembly.
AB  - The PA700-like proteasome activator complex was highly purified from porcine
      erythrocytes, and its properties were compared with those of the regulatory
      complex disassembled from the purified 26S proteasome. The molecular mass of the
      PA700-like complex, which comprises 25-110-kDa subunits, was estimated to be 800
      kDa by Superose 6 gel filtration. This complex showed neither ATPase activity nor
      peptidase activity toward Suc-Leu-Leu-Val-Tyr-MCA. Nevertheless, it was possible
      to make a high molecular mass complex from the purified PA700-like complex by
      incubating with the 20S proteasome in the presence of ATP. In contrast, the
      regulatory complex dissociated from the 26S proteasome did not reconstitute a
      larger complex under the same conditions. The subunit composition of the PA700
      like complex was similar but not identical to that of the regulator complex
      dissociated from the 26S proteasome: the former complex had a 25-kDa subunit
      which is absent in the latter, whereas the latter had two or three 43-kDa
      subunits lacking in the former. These results indicate that the purified PA700
      like proteasome activator complex is structurally and functionally distinct from
      the regulatory complex dissociated from the 26S proteasome, implying the
      involvement of modulating factors in the 26S proteasome assembly.

PMID- 9276460
TI  - Characterization of membrane-associated prothrombin activator in normal and
      injured murine tissues.
AB  - Thrombin is a multifunctional enzyme involved in coagulation, cell modulation and
      inflammation. We recently reported a novel membrane-associated prothrombin
      activator, abbreviated as MAPA, found in cultured fibroblasts and glial cell
      lines. In this study, we examined the physiological role of this enzyme. MAPA
      like activity was detected in the liver, kidney, lung and heart but not in the
      spleen or brain in normal mice. To examine whether MAPA participates in
      biological reactions, hepatic and renal injury were induced by administration of
      CCl4 and HgCl2, respectively. MAPA-like activity was specifically increased in
      the injured tissues: the activity was elevated by about 100-fold in 48 h in the
      liver and increased by about 5-fold in 12 h in the kidney. Their enzymatic
      properties were the same as those of MAPA in 8C feline kidney fibroblast cells.
      Phospholipids are required for activation of prothrombin by MAPA obtained from
      both 8C cells and tissues. These results suggest that MAPA activates prothrombin
      on the cell surface in injured tissue and participates in inflammation and
      regeneration associated with tissue injury.

PMID- 9276461
TI  - Expression of PEP carboxylase from Escherichia coli complements the phenotypic
      effects of pyruvate carboxylase mutations in Saccharomyces cerevisiae.
AB  - We investigated the effects of the expression of the Escherichia coli ppc gene
      encoding PEP carboxylase in Saccharomyces cerevisiae mutants devoid of pyruvate
      carboxylase. Functional expression of the ppc gene restored the ability of the
      yeast mutants to grow in glucose-ammonium medium. Growth yield in this medium was
      the same in the transformed yeast than in the wild type although the growth rate
      of the transformed yeast was slower. Growth in pyruvate was slowed down in the
      transformed strain, likely due to a futile cycle produced by the simultaneous
      action of PEP carboxykinase and PEP carboxylase.

PMID- 9276462
TI  - Translocation of NLS-BSA conjugates into nuclei of permeabilized mammalian cells
      can be supported by protoplast extract. An experimental system for studying plant
      cytosolic factors involved in nuclear import.
AB  - An heterologous experimental system, which allows the study of the yet unknown
      cytosolic factors involved in nuclear import of nuclear localization signal (NLS)
      containing proteins in plants, has been established. The ability of plant cell
      extract to substitute mammalian cytosol and to promote translocation of NLS
      containing proteins into nuclei of permeabilized HeLa cells was demonstrated. The
      results described in the present work show that nuclear import of fluorescently
      labeled BSA conjugates bearing the NLS sequence of SV40 large T antigen could be
      supported by petunia cell cytoplasmic extract. This heterologous system shows the
      characteristic features of the homologous mammalian system, namely, is ATP
      dependent and is inhibited by WGA, GTPgammaS as well as by non-fluorescent NLS
      BSA conjugates. The system described here offers an experimental method to study
      and characterise cytosolic factors which are required for nuclear import in
      plants.

PMID- 9276463
TI  - Intermittent divergence of the protein tyrosine kinase family during animal
      evolution.
AB  - The protein tyrosine kinases (PTKs) are a large protein family consisting of many
      subfamilies with a variety of domain structures. The basic functions are thought
      to differ for different subfamilies. To know the dates at which the subfamilies
      diverged by gene duplications, a phylogenetic tree of the PTKs was inferred by
      comparing sequences from a wide range of species covering diploblasts and
      triploblasts. The PTK tree revealed that almost all of the gene duplications that
      gave rise to different subfamilies occurred rapidly before the diploblast
      triploblast split, accompanying with rapid amino acid substitutions. This type of
      gene duplication was, however, rarely observed after that split. Long after the
      subfamily divergence, another type of gene duplication that gave rise to diverse
      tissue-specific genes occurred in each subfamily on the chordate lineage since
      the separation from arthropods. This type of gene duplication occurred frequently
      before the fish-tetrapod split, accompanying with rapid amino acid substitutions.
      In contrast, both the frequency of gene duplications and the rate of the amino
      acid substitutions were considerably reduced after that split. These results
      strongly suggest that the PTKs diverged intermittently, but not gradually, during
      animal evolution.

PMID- 9276464
TI  - Substrate specificity of alpha-1,6-mannosyltransferase that initiates N-linked
      mannose outer chain elongation in Saccharomyces cerevisiae.
AB  - Yeast Saccharomyces cerevisiae OCH1 gene encodes the mannosyltransferase that is
      essential for the outer chain elongation of N-linked oligosaccharides.
      Mannosyltransferase activity of OCH1 gene product (Och1p) was measured on HPLC by
      using pyridylaminated Man8GlcNAc2 (Man8GlcNAc2-PA) as an acceptor and the
      reaction product was observed at the retention time corresponding to Man9GlcNAc2
      PA. 1H-NMR and fast atom bombardment mass spectrometry (FAB-MS) fragmentation
      analysis of Man9GlcNAc2-PA showed that the additional mannose was attached with
      an alpha-1,6 linkage at the site where mannose outer chain elongation initiates.
      Substrate specificity of Och1p was investigated by using various high mannose
      type oligosaccharides as acceptors. Man8GlcNAc2 was the best acceptor for Och1p.
      The loss of one or two alpha-1,2-mannoses from Man8GlcNAc2 reduced the
      mannosyltransferase activity and the Man5GlcNAc2 completely lacking alpha-1,2
      mannose residues did not serve as an acceptor. Man8GlcNAcOH that involves an open
      sugar ring by reduction of reducing terminal GlcNAc residue did not serve as an
      acceptor for Och1p. The loss of three mannoses at the alpha-1,6-branch also
      reduced the Och1p activity. These results suggest that Och1p is an initiation
      specific alpha-1,6-mannosyltransferase that requires the intact structure of
      Man8GlcNAc for efficient mannose outer chain initiation.

PMID- 9276465
TI  - Quail cystatin: isolation and characterisation of a new member of the cystatin
      family and its hypothetical interaction with cathepsin B.
AB  - Quail cystatin, a new cysteine proteinase inhibitor protein of the cystatin
      superfamily, was purified from egg albumen of Japanese quail Coturnix coturnix
      japonica. Amino acid sequencing and mass spectrometry revealed the complete 116
      amino acid residue primary structure of a phosphorylated form (13,173 Da). The
      inhibitor has a 90% sequence identity with chicken cystatin. Its interaction with
      papain is rapid and tight (Ki = 4.4 pM; k(on) = 1.8x10(7) M(-1) s(-1); k(off) =
      0.8x10(-4) s(-1)) and very similar to that of chicken cystatin. Surprisingly,
      however, cathepsin B was inhibited 15-fold more strongly by quail cystatin (Ki =
      47 pM; k(on) = 19x10(7) M(-1) s(-1); k(off) = 9x10(-4) s(-1)) than by chicken
      cystatin (Ki = 784 pM; k(on) = 2.9x10(7) M(-1) s(-1); k(off) = 24x10(-4) s(-1)).
      Intuitive comparative conformational inspection of related inhibitors and of
      cognate enzymes suggest that: (i) the 3D structure of quail cystatin is nearly
      identical to that of chicken cystatin, (ii) quail cystatin can interact with
      cathepsin B analogous to the stefin B-papain interaction, if the 'occluding loop'
      of cathepsin B possesses an 'open' conformation, (iii) the greater inhibition of
      cathepsin B by quail cystatin compared to chicken cystatins probably arises from
      two additional ionic interactions between residues Arg15 and Lys112 of the
      inhibitor and Glu194 and Asp124 of the enzyme, respectively. The two potential
      salt bridges are located outside of the known contact regions between cystatins
      and peptidases of the papain family.

PMID- 9276466
TI  - Human histidine-rich glycoprotein expressed in SF9 insect cells inhibits apatite
      formation.
AB  - Histidine-rich glycoprotein (HRG) is structurally related to the alpha2-HS
      glycoprotein/fetuin family of mammalian plasma proteins; both belong to the
      cystatin superfamily of proteins. We expressed recombinant human HRG and alpha2
      HS in Sf9 insect cells for functional analysis. Recombinant HRG bound heparin and
      fibrinogen while alpha2-HS did not. Both proteins inhibited the formation of
      apatite, recombinant HRG (IC50 approximately 1 microM) with 2-fold lower molar
      activity than alpha2-HS (IC50 approximately 0.5 microM). The inhibition in vitro
      of apatite formation suggests a new function for plasma HRG protein, inhibition
      of phase separation in blood vessels.

PMID- 9276467
TI  - Structural and functional characterisation of two proteolytic fragments of the
      bacterial protein toxin, pneumolysin.
AB  - Proteolytic cleavage of the bacterial protein toxin pneumolysin with protease K
      creates two fragments of 37 and 15 kDa. This paper describes the purification of
      these two fragments and their subsequent physical and biological
      characterisation. The larger fragment is directly involved in the cytolytic
      mechanism of this pore-forming protein, via membrane binding and self
      association. The smaller fragment lacks ordered structure or discernible
      activity.

PMID- 9276468
TI  - Calcium influx inhibits MT1-MMP processing and blocks MMP-2 activation.
AB  - We have previously reported that concanavalin A (ConA)-induced MMP-2 activation
      involves both transcriptional and non-transcriptional mechanisms. Here we
      examined the effects of calcium influx on MT1-MMP expression and MMP-2 activation
      in MDA-MB-231 cells. The calcium ionophore ionomycin caused a dose-dependent
      inhibition of ConA-induced MMP-2 activation, but had no effect on MT1-MMP mRNA
      levels. However, Western analysis revealed an accumulation of pro-MT1-MMP (63
      kDa), indicating that ionomycin blocked the conversion of pro-MT1-MMP protein to
      the active 60 kDa form. This suggests that increased calcium levels inhibit the
      processing of MT1-MMP. This finding may help to elucidate the mechanism(s) which
      regulates MT1-MMP activation.

PMID- 9276469
TI  - Crystal structure of vipoxin at 2.0 A: an example of regulation of a toxic
      function generated by molecular evolution.
AB  - Vipoxin is the main toxic component in the venom of the Bulgarian snake Vipera
      ammodytes meridionalis, the most toxic snake in Europe. Vipoxin is a complex
      between a toxic phospholipase A2 (PLA2) and a non-toxic protein inhibitor. The
      structure is of genetic interest due to the high degree of sequence homology
      (62%) between the two functionally different components. The structure shows that
      the formation of the complex in vipoxin is significantly different to that seen
      in many known structures of phospholipases and contradicts the assumptions made
      in earlier studies. The modulation of PLA2 activity is of great pharmacological
      interest, and the present structure will be a model for structure-based drug
      design.

PMID- 9276470
TI  - Different distribution of phosphorylated tau protein isoforms in Alzheimer's and
      Pick's diseases.
AB  - Tau proteins aggregate into different neuronal inclusions in several
      neurodegenerative disorders. In Alzheimer's disease (AD), hyperphosphorylated Tau
      from paired helical filaments (PHF) of neurofibrillary tangles, named PHF-Tau,
      have an electrophoretic profile with four main bands (Tau 55, 64, 69, 74 kDa). In
      Pick's disease, phosphorylated Tau from Pick bodies are made of two major
      components (Tau 55, 64 kDa) and a minor 69 kDa. Here we show, using specific
      antibodies against translated exon 2, 3 or 10 of Tau isoforms, that the set of
      Tau isoforms engaged in the most insoluble part of PHF in AD is made of Tau
      isoforms with exon 10 while they are lacking in phosphorylated Tau from Pick's
      disease. Our results suggest that specific sets of Tau isoforms distinguish
      between typical neuronal inclusions.

PMID- 9276471
TI  - Activation of transcription factor NF-kappa B by phagocytic stimuli in human
      neutrophils.
AB  - Phagocytosis represents an important physiological trigger for the inducible
      expression of several genes in human neutrophils. Here, we report that a DNA
      binding activity primarily consisting of the classical NF-kappa B heterodimer,
      p50/RelA, is induced in phagocytosing neutrophils. Under these conditions, NF
      kappa B activation was found to be a rapid and transient response, reaching a
      maximum by 10-15 min, and returning to near-basal levels by 30 min. In
      neutrophils undergoing the phagocytosis of opsonized yeasts, the onset of NF
      kappa B activation was paralleled by a decline in immunoreactive I kappa B-alpha
      protein levels, and the cellular I kappa B-alpha pool was replenished by 30 min,
      in agreement with our gel shift data. We conclude that NF-kappa B activation
      could constitute one of the mechanisms whereby the expression of kappa B
      responsive genes is enhanced in phagocytosing neutrophils. To our knowledge, this
      represents the first demonstration that phagocytic stimuli can induce NF-kappa B
      activation in human neutrophils.

PMID- 9276472
TI  - Simultaneous production of the 34-kDa and 40-kDa proteins from Bacillus
      thuringiensis subsp. thompsoni is required for the formation of inclusion bodies.
AB  - Cooperation of two crystal proteins from Bacillus thuringiensis subsp. thompsoni.
      strain HnC was shown to be essential for the formation of inclusion bodies.
      Expression of the operon containing the 34-kDa and 40-kDa protein genes from HnC
      in a B. thuringiensis crystal minus strain resulted in the formation of inclusion
      bodies identical to those from strain HnC. Interruption of one of the genes in
      the operon led to the lack of inclusion body and to low production of the
      remaining protein. Absence of inclusion body and low rate of protein production
      were also observed when both genes were simultaneously expressed but on different
      vectors. To show a cooperative effect in the formation of the inclusion body,
      both proteins must be produced from the same transcript.

PMID- 9276473
TI  - Novel components and enzymatic activities of the human erythrocyte plasma
      membrane calcium pump.
AB  - The plasma membrane Ca2+ pump is essential for the maintenance of cystolic
      calcium ion concentration levels in eukaryotes. Here we show that the Ca2+
      ATPase, purified from human erythrocytes, contains two homopolymers, poly(3
      hydroxybutyrate) (PHB) and inorganic polyphosphate (polyP), which form voltage
      activated calcium channels in the plasma membranes of Escherichia coli and other
      bacteria. Furthermore, we demonstrate that the plasma membrane Ca2+-ATPase may
      function as a polyphosphate kinase, i.e. it exhibits ATP-polyphosphate
      transferase and polyphosphate-ADP transferase activities. These findings suggest
      a novel supramolecular structure for the functional Ca2+-ATPase, and a new
      mechanism of uphill Ca2+ extrusion coupled to ATP hydrolysis.

PMID- 9276474
TI  - Involvement of HNF-1 in the regulation of phosphoenolpyruvate carboxykinase gene
      expression in the kidney.
AB  - The cytosolic form of phosphoenolpyruvate carboxykinase (GTP) (PEPCK) gene is
      differentially expressed in several tissues. A specific set of regulatory
      elements in the promoter are responsible for the control of PEPCK gene
      transcription and, in turn, determine its distinct metabolic role in each tissue.
      DNase I footprinting analysis of the PEPCK promoter, using nuclear proteins from
      tissues which express the gene for PEPCK, and transient expression assays in
      renal cell lines have demonstrated that the HNF-1 recognition motif (P2) in the
      PEPCK promoter characterizes kidney-specific expression. This site is required
      also for the response to acidosis. Since the P2 site is not involved in the
      expression of the PEPCK gene in the liver, we propose that its critical role in
      the kidney stems from a combination of abundance of HNF-1 together with low
      concentrations of members of the C/EBP family in this tissue.

PMID- 9276475
TI  - Granulocytic differentiation of HL-60 cells results in spontaneous apoptosis
      mediated by increased caspase expression.
AB  - HL-60 cells differentiating into neutrophil-like cells die an apoptotic death in
      vitro. Susceptibility to apoptosis is associated with decreased Bcl-2 protein and
      mRNA expression; however, the effect of differentiation on the expression of pro
      apoptotic caspases is unknown. Spontaneous apoptosis occurred 6 days after
      retinoic acid treatment. Western blotting showed loss of Bcl-2 by day 7, and new
      expression of ICE (caspase 1) and CPP32 (caspase 3) protein by day 2. Northern
      analysis demonstrated loss of Bcl-2 mRNA and increases in ICE mRNA by day 2;
      CPP32 mRNA was unchanged. Differential Bcl-2 and ICE mRNA expression was also
      found when granulocytic differentiation was stimulated by DMSO. Differentiated HL
      60 cell lysates exhibited functional ICE proteolytic activity. De novo caspase
      expression was responsible for the development of spontaneous apoptosis, since
      specific inhibitors of ICE (YVAD-CMK) and CPP32 (DEVD-CHO), inhibited retinoic
      acid induced spontaneous apoptosis. Functional maturation and susceptibility to
      apoptosis are both inducible and linked in this granulocyte precursor cell line.

PMID- 9276476
TI  - Mutagenesis of residues 27 and 78 modulates heme orientation in cytochrome b5.
AB  - A comparison of the primary sequences of the heme binding domains of bovine and
      rat microsomal cytochrome reveal differences at only six residues. These residues
      must therefore provide the origin for the observed variation in the ratio of the
      heme orientational isomers, the equilibrium constant of which ranges from
      approximately 9 in the bovine protein to 1.6 for rat cytochrome b5. Residues 7,
      20, 21, and 30 are distant from the exposed heme edge whilst Leu27 and Phe78 are
      located close to different parts of the porphyrin macrocycle. 1H NMR spectra of
      the heme and heme ligand resonances of a recombinant tobacco cytochrome b5
      extending from Gly1 to Lys89 suggest, in combination with NMR data acquired for
      other forms of cytochrome b5 and an inspection of their sequence homology, that
      the identity of residue 78 influences the relative ratios of heme isomers. The
      Gly1-Lys89 domain of tobacco cytochrome b5 has two equally abundant heme
      orientational isomers but retains the leucine side chain at position 27 whilst
      phenylalanine 78 is replaced by tyrosine. A more direct role for residue 78 in
      modulating the heme ratio is shown by site directed mutagenesis of bovine
      microsomal cytochrome b5 where the mutation Phe78 > Tyr shifts the equilibrium
      constant for the heme orientational isomers from 9 to 3.5. Whilst the ratio is
      clearly shifted towards that exhibited by the rat protein the incomplete
      transition suggested the involvement of other residues. The mutation of Leu27 >
      Val was shown to result in a slightly smaller change in ratios of each isomer
      (from 9 to 4.0). Together these results point to the importance of these residues
      in modulating the ratio of heme isomers.

PMID- 9276477
TI  - Neutral trehalase Nth1p of Saccharomyces cerevisiae encoded by the NTH1 gene is a
      multiple stress responsive protein.
AB  - We have shown previously that expression of the NTH1 gene is increased at heat
      stress (40 degrees C) both at the mRNA and enzymatic activity levels. This
      increased expression was correlated to the requirement of the NTH1 gene for
      recovery after heat shock at 50 degrees C and the presence of stress responsive
      elements STRE (CCCCT) 3 times in its promoter region [S. Nwaka et al., FEBS Lett.
      360 (1995) 286-290; S. Nwaka et al., J. Biol. Chem. 270 (1995) 10193-10198]. We
      show here that expression of the NTH1 gene and its product, neutral trehalase
      (Nthlp), are also induced by other stressors such as H2O2, CuSO4, NaAsO2, and
      cycloheximide (CHX). Heat-induced expression of the NTH1 gene is shown to be
      accompanied by accumulation of trehalose. In contrast, the chemical stressors
      which also induce the expression of NTH1 did not lead to accumulation of
      trehalose under similar conditions. Our data suggest that: (1) heat- and chemical
      stress-induced expression of neutral trehalase is largely due to de novo protein
      synthesis, and (2) different mechanisms may control the heat- and chemical stress
      induced expression of NTH1 at the transcriptional level. Participation of neutral
      trehalase (Nth1p) in multiple stress response dependent and independent on
      trehalose is discussed.

PMID- 9276478
TI  - Myotonic dystrophy kinase modulates skeletal muscle but not cardiac voltage-gated
      sodium channels.
AB  - Altered modulation of skeletal muscle voltage-gated sodium channels by myotonic
      dystrophy kinase (DMPK) has been proposed as a possible mechanism underlying
      myotonia in this disease. We examined the effect of a recombinant mouse DMPK on
      the functional properties of human skeletal muscle (hSkM1) and cardiac (hH1)
      voltage-gated sodium channels in the Xenopus oocyte expression system. Co
      expression of DMPK with hSkM1 in oocytes resulted in significantly lower peak
      sodium current amplitude as compared to cells expressing hSkM1 alone in agreement
      with a previous report. By contrast, DMPK had no effect on the level of expressed
      sodium current in cells expressing hH1. Similarly, there were no measurable
      effects of the kinase on the kinetics or steady-state properties of activation or
      inactivation. Our findings support the previous observations made with rat muscle
      sodium channels and demonstrate that the effect of DMPK on sodium channels is
      isoform specific despite conservation of a putative phosphorylation site between
      the two isoforms.

PMID- 9276479
TI  - Cooperative thermal transitions of bovine and human apo-alpha-lactalbumins:
      evidence for a new intermediate state.
AB  - The thermal denaturation of bovine and human apo-alpha-lactalbumins at neutral pH
      has been studied by intrinsic protein fluorescence, circular dichroism (CD), and
      differential scanning microcalorimetry (DSC) methods. Apo-alpha-lactalbumin
      possesses a thermal transition with a midpoint about 25-30 degrees C under these
      conditions (pH 8.1, 10 mM borate, 1 mM EGTA), which is reflected in changes in
      both fluorescence emission maximum and quantum yield. However, the CD showed a
      decrease in ellipticity at 270 nm with a midpoint at about 10-15 degrees C, while
      DSC shows the transition within the region of 15-20 degrees C. The non
      coincidence of transition monitored by different methods suggests the existence
      of an intermediate state in the course of the thermal denaturation process. This
      intermediate state is not the classical molten globule state which occurs at
      higher temperature (i.e. denatured state at these conditions) [D.A. Dolgikh, R.I.
      Gilmanshin, E.V. Brazhnikov, V.E. Bychkova, G.V. Semisotnov, S.Y. Venyaminov and
      O.B. Ptitsyn, FEBS Letters, 136 (1981) 311-315] and has physical properties
      intermediate between the native and molten globule states.

PMID- 9276480
TI  - Aging decreases the abundance of retinoic acid (RAR) and triiodothyronine (TR)
      nuclear receptor mRNA in rat brain: effect of the administration of retinoids.
AB  - Aging is accompanied by troubles resulting from changes in hormonal and
      nutritional status. Therefore, the abundance of mRNA coding for triiodothyronine
      (TR) and retinoic acid (RA) nuclear receptors was studied in the brain of young,
      adult and aged (2.5, 6 and 24 months, respectively) rats. In the brain of aged
      rats, there was a lower abundance of TR and RAR mRNA and a lower activity of
      tissue transglutaminase (tTG), an enzyme the gene of which is a target for
      retinoids. Administration of RA in these rats restored TR and RAR mRNA and the
      activity of tTG in the brain. The importance of these observations to the
      function of the aged brain is discussed.

PMID- 9276481
TI  - K+ is an indispensable cofactor for GrpE stimulation of ATPase activity of DnaK x
      DnaJ complex from Thermus thermophilus.
AB  - K+ is an indispensable cofactor for ATPase activity of eukaryotic cytosolic Hsp70
      chaperone systems which lack a GrpE homolog. In the case of the bacterial Hsp70
      (DnaK) system, GrpE, a nucleotide exchange factor, stimulates ATPase activity but
      little is known about the effect of K+. Here, we have cloned a grpE gene from a
      thermophile, Thermus thermophilus, and purified a homodimeric GrpE protein. Using
      proteins of this bacterium, we found that the GrpE stimulation of ATPase activity
      of DnaK x DnaJ complex was absolutely dependent on the presence of K+.

PMID- 9276482
TI  - The beta 1,6-GlcNAc transferase activity present in hog gastric mucosal
      microsomes catalyses site-specific branch formation on a long polylactosamine
      backbone.
AB  - We find that the beta 1,6-GlcNAc transferase activity present in hog gastric
      mucosal microsomes converts the linear pentasaccharide GlcNAc beta 1-3Gal beta 1
      4GlcNAc beta 1-3Gal beta 1-4GlcNAc (1) in a site-specific way to the branch
      bearing hexasaccharide GlcNAc beta 1-3(GlcNAc beta 1-6)Gal beta 1-4GlcNAc beta 1
      3Gal beta 1-4GlcNAc (2). The product is a positional isomer of GlcNAc beta 1-3Gal
      beta 1-4GlcNAc beta 1-3(GlcNAc beta 1-6)Gal beta 1-4GlcNAc (3), reportedly formed
      from 1 by another polylactosamine beta 1,6-GlcNAc transferase activity present in
      human serum (Leppanen et al., Biochemistry, 30 (1991) 9287). Combined use of the
      two kinds of activities gave in the present experiments the heptasaccharide
      GlcNAc beta 1-3(GlcNAc beta 1-6)Gal beta 1-4GlcNAc beta 1-3(GlcNAc beta 1-6)Gal
      beta 1-4GlcNAc (4), in which one of the branches occupies the position of the
      branch in 2 and the other the position of the branch in 3.

PMID- 9276483
TI  - Formation of a 2-methyl-branched fatty aldehyde during peroxisomal alpha
      oxidation.
AB  - In the final reaction of peroxisomal alpha-oxidation of 3-methyl-branched fatty
      acids a 2-hydroxy-3-methylacyl-CoA intermediate is cleaved to formyl-CoA and a
      hitherto unidentified product. The release of formyl-CoA suggests that the
      unidentified product may be a fatty aldehyde. When purified rat liver peroxisomes
      were incubated with 2-hydroxy-3-methylhexadecanoyl-CoA 2-methylpentadecanal was
      indeed formed. The production rates of formyl-CoA (measured as formate) and of
      the aldehyde were in the same range. While the production of formate remained
      unaltered in the presence of NAD+, the amount of 2-methylpentadecanal was
      decreased, which was accompanied by the formation of 2-methylpentadecanoic acid.
      These data indicate that (1) during alpha-oxidation the 2-hydroxy-3-methylacyl
      CoA is cleaved to a 2-methyl-branched aldehyde and formyl-CoA and (2) liver
      peroxisomes are capable of converting this aldehyde to a 2-methyl-branched fatty
      acid.

PMID- 9276484
TI  - An abnormal distribution of melatonin receptors in the newborn rat with inherited
      prenatal hydrocephalus.
AB  - Melatonin binding in the brain of hydrocephalic H-Tx rats was examined by
      autoradiography. At the time of birth, hydrocephalic animals showed an
      abnormality in the distribution of high-affinity melatonin receptors dorsal to
      the cerebral aqueduct when compared to controls. Whereas newborn rats of the H-Tx
      strain that were unaffected by hydrocephalus had melatonin receptors in a tectal
      midsagittal strip overlying the aqueduct and spanning the anterior half of the
      tectum, hydrocephalic rats lacked melatonin receptors in the most anterior part
      of this region. In these animals, the length of the aqueduct over which receptors
      were missing was compressed and was additionally occluded by dystrophic ependyma.
      The first signs of ventricular expansion characteristic of hydrocephalus were
      evident.

PMID- 9276485
TI  - Alzheimer's amyloid-beta peptide inhibits sodium/calcium exchange measured in rat
      and human brain plasma membrane vesicles.
AB  - Na+/Ca2+ exchange activity was measured by monitoring vesicular Ca2+ content
      after incubation in buffers containing 45Ca2+. When Na+-loaded vesicles were
      placed into Na+-free buffer, vesicular Ca2+ content increased rapidly and reached
      a plateau after two to three minutes. Only preaggregated amyloid-beta1-40 (Abeta1
      40) and Abeta25-35 reduced vesicular Ca2+ content. Both peptides produced a
      maximal reduction in Ca2+ content of approximately 50%. The peptides reduced Ca2+
      content with similar potency and half maximal effects were seen at less than 10
      microM for Abeta25-35. Calcium-loaded vesicles mediate a rapid Ca2+/Ca2+
      exchange, which also was inhibited by aggregated Abeta25-35. Aggregated Abeta25
      35 did not affect the passive Ca2+ permeability of the vesicles. Aggregated
      Abeta25-35 reduced Ca2+ content in plasma membrane vesicles isolated from normal
      and Alzheimer's disease frontal cortex with less potency but the same efficacy as
      seen in rat brain. Aggregated Abeta25-35 did not produce nonspecific effects on
      vesicle morphology such as clumping or loss of intact vesicles. When placed in
      the buffer used to measure Ca2+ content, Congo Red at molar ratios of less than
      one blocked the inhibitory effect of preaggregated Abeta25-35. When added in
      equimolar concentrations to freshly dissolved and unaggregated Abeta25-35, Congo
      Red also was effective at blocking the inhibitory effect on Ca2+ content. In
      contrast, vitamin E (antioxidant) and N-tert-butyl-alpha-phenylnitrone (spin
      trapping agent) failed to block the inhibitory action of aggregated Abeta25-35.
      The exact mechanisms of Abeta-induced neurotoxicity in cell culture has yet to be
      solved. Accumulation of free radicals play a necessary role, but disruptions of
      Ca2+ homeostasis are also important. The data presented here are consistent with
      a proposed mechanism where aggregated Abeta peptides directly interact with
      hydrophobic surfaces of the exchanger protein and/or lipid bilayer and interfere
      with plasma membrane Ca2+ transport.

PMID- 9276486
TI  - 4-Hydroxynonenal, an aldehydic product of membrane lipid peroxidation, impairs
      glutamate transport and mitochondrial function in synaptosomes.
AB  - Removal of extracellular glutamate at synapses, by specific high-affinity
      glutamate transporters, is critical to prevent excitotoxic injury to neurons.
      Oxidative stress has been implicated in the pathogenesis of an array of prominent
      neurodegenerative conditions that involve degeneration of synapses and neurons in
      glutamatergic pathways including stroke, and Alzheimer's, Parkinson's and
      Huntington's diseases. Although cell culture data indicate that oxidative insults
      can impair key membrane regulatory systems including ion-motive ATPases and amino
      acid transport systems, the effects of oxidative stress on synapses, and the
      mechanisms that mediate such effects, are largely unknown. This study provides
      evidence that 4-hydroxynonenal, an aldehydic product of lipid peroxidation,
      mediates oxidation-induced impairment of glutamate transport and mitochondrial
      function in synapses. Exposure of rat cortical synaptosomes to 4-hydroxynonenal
      resulted in concentration- and time-dependent decreases in [3H]glutamate uptake,
      and mitochondrial function [assessed with the dye 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide (MTT)]. Other related aldehydes including
      malondialdehyde and hexanal had little or no effect on glutamate uptake or
      mitochondrial function. Exposure of synaptosomes to insults known to induce lipid
      peroxidation (FeSO4 and amyloid beta-peptide) also impaired glutamate uptake and
      mitochondrial function. The antioxidants propyl gallate and glutathione prevented
      impairment of glutamate uptake and MTT reduction induced by FeSO4 and amyloid
      beta-peptide, but not that induced by 4-hydroxynonenal. Western blot analyses
      using an antibody to 4-hydroxynonenal-conjugated proteins showed that 4
      hydroxynonenal bound to multiple cell proteins including GLT-1, a glial glutamate
      transporter present at high levels in synaptosomes. 4-Hydroxynonenal itself
      induced lipid peroxidation suggesting that, in addition to binding directly to
      membrane regulatory proteins, 4-hydroxynonenal potentiates oxidative cascades.
      Collectively, these findings suggest that 4-hydroxynonenal plays important roles
      in oxidative impairment of synaptic functions that would be expected to promote
      excitotoxic cascades.

PMID- 9276487
TI  - Conditioned responses of monkey locus coeruleus neurons anticipate acquisition of
      discriminative behavior in a vigilance task.
AB  - Impulse activity was recorded extracellularly from noradrenergic neurons in the
      nucleus locus coeruleus of three cynomolgus monkeys performing a visual
      discrimination (vigilance) task. For juice reward, the subjects were required to
      release a lever rapidly in response to an improbable target stimulus (20% of
      trials) that was randomly intermixed with non-target stimuli presented on a video
      display. All locus coeruleus neurons examined were phasically and selectively
      activated by target stimuli in this task. Other task events elicited no
      consistent response from these neurons (juice reward, lever release, fix spot
      stimuli, non-target stimuli). With reversal of the task contingency, locus
      coeruleus neurons ceased responding to the former target stimuli, and began
      responding instead to the new target (old non-target) stimuli. In addition, the
      latency of locus coeruleus response to target stimuli increased after reversal
      (by about 140 ms) in parallel with a similar increase in the latency of the
      behavioral response. These results indicate that the conditioned locus coeruleus
      responses reflect stimulus meaning and cognitive processing, and are not driven
      by physical sensors attributes. Notably, the reversal in locus coeruleus response
      to stimuli after task reversal occurred rapidly, hundreds of trials before
      reversal was expressed in behavioral responses. These findings indicate that
      conditioned responses of locus coeruleus neurons are plastic and easily altered
      by changes in stimulus meaning, and that the locus coeruleus may play an active
      role in learning the significance of behaviorally important stimuli.

PMID- 9276488
TI  - Contrasting effects of excitotoxic lesions of the prefrontal cortex on the
      behavioural response to D-amphetamine and presynaptic and postsynaptic measures
      of striatal dopamine function in monkeys.
AB  - The effects of excitotoxic lesions of the prefrontal cortex on behavioural,
      neurochemical and molecular indices of dopamine function in the caudate nucleus
      were studied in the marmoset. The lesion, which encompassed both the lateral and
      orbital regions of prefrontal cortex, made the animals more sensitive to the
      performance disrupting effects of the dopamine releasing drug, D-amphetamine, in
      a variation of the object retrieval task. Specifically, following drug
      administration, the lesioned marmosets were less able to gain access to food
      reward in the minimum number of responses. Analysis of the nature of the errors
      suggested that the deficit was not due to inhibition of a prepotent response as
      the lesioned monkeys were just as likely to make a detour reach to the unopened
      side of the box as a direct "line-of-sight" reach into the unopened front of the
      box. Rather, the data indicated a general disorganization of behaviour. The
      enhanced behavioural responsiveness to manipulations increasing presynaptic
      dopamine function was accompanied by neurochemical changes indicating a reduced
      responsiveness, as revealed by in vivo microdialysis. Thus, in lesioned animals,
      whilst there were no effects on baseline levels of extracellular dopamine in
      dorsolateral caudate, evoked release, both to systemic D-amphetamine and to a
      local depolarizing pulse of potassium ions, was attenuated. These opposite
      effects of the prefrontal cortex lesion on behavioural and neurochemical indices
      of striatal dopamine function occurred in the absence of any changes in striatal
      dopamine receptors of the D1 and D2 subtype, as determined both by radioligand
      binding assays and measurements of messenger RNA using in situ hydridization
      techniques. These data provide further insight into the interactions between
      prefrontal cortex and striatal dopamine function in the non-human primate. In
      particular, when taken in the light of our previous studies they indicate that
      following prefrontal manipulations, concurrence between behavioural and
      neurochemical indices of striatal dopamine function depends, critically, on the
      behavioural task. These findings are discussed with respect to the growing body
      of evidence implicating abnormalities in frontostriatal neurotransmission in
      complex disorders such as schizophrenia.

PMID- 9276489
TI  - Cholinergic sprouting in the rat fascia dentata after entorhinal lesion is not
      linked to early changes in neurotrophin messenger RNA expression.
AB  - After unilateral entorhinal cortex lesion cholinergic septohippocampal fibres
      sprout in the denervated fascia dentata. This process is dependent on
      neurotrophin changes following the lesion. Thus, there is an up-regulation of
      nerve growth factor and brain-derived neurotrophic factor messenger RNA
      expression in the denervated granule cells which is detectable 4 h postlesion and
      returns to control levels by 24 h. Here, using a competitive polymerase chain
      reaction and in situ hybridization, a transient neurotropin messenger RNA
      increase could be demonstrated bilaterally following unilateral electrolytic
      entorhinal cortex lesion. Treatment of the animals with the N-methyl-D-aspartate
      receptor antagonist dizocilpine maleate blocked this messenger RNA increase,
      suggesting an involvement of this receptor type in the neurotrophin changes.
      However, in spite of this blockade, the typical cholinergic sprouting response as
      visualized with acetylcholinesterase histochemistry was present in animals four
      weeks after entorhinal cortex lesion. These data suggest that brief initial
      changes in neurotrophin messenger RNA expression in dentate granule cells are not
      responsible for the induction of the cholinergic sprouting. Changes in
      neurotrophin messenger RNA expression occurring immediately postlesion may be
      linked to glutamate release from entorhinal terminals resulting from the
      electrolytic lesion of the projection cells in the entorhinal cortex. We
      hypothesize that later changes in neurotrophin expression, for example in glial
      cells, are more likely to be related to the cholinergic sprouting process.

PMID- 9276490
TI  - Specificity of attachment and neurite outgrowth of dissociated basal forebrain
      cholinergic neurons seeded on to organotypic slice cultures of forebrain.
AB  - Development and differentiation of basal forebrain-derived cholinergic neurons
      were studied using a new technique that combines dissociated cell cultures with
      organotypic slice cultures. Slices of cerebral cortex or entire forebrain
      hemispheres were taken from early postnatal rat pups and maintained as
      organotypic cultures on membranes. Dissociated cell suspensions of basal
      forebrain tissue, taken from rat or mouse fetuses at gestational day 15-17, were
      seeded on to the slice cultures. Combined cultures were maintained for two to 14
      days in vitro. Cultures processed for acetylcholinesterase histochemical staining
      demonstrated that stained neurons display regional variation in attachment to the
      slice, with most attachment occurring on cortex and with no detectable attachment
      on the caudate-putamen. Regional differences in attachment occur between cortical
      areas, with medial (cingulate) cortex showing much denser cell attachment than
      lateral (parietal) cortex, and across cortical layers, with layer I and deep
      layers showing more attachment than middle cortical layers. Similar patterns were
      observed on slices from rat brain irrespective of whether rat or mouse
      dissociated cells were used. Tyrosine hydroxylase-stained dissociated cells from
      ventral midbrain displayed a different pattern of attachment, with prominent
      attachment to the caudate putamen and less apparent specificity of regional and
      cortical laminar attachment. Little evidence of neurite outgrowth occurred during
      the first two days in vitro, but by four days, acetylcholinesterase-positive
      basal forebrain cells displayed several short and thick neurites that appeared to
      be dendrites, and one long process that appeared to be an axon. By seven days in
      vitro, dendrites are well developed and the presumed axon has extended branches
      over wide areas of cortex. These studies revealed several different types of cell
      tissue interaction. The degree of cell growth and differentiation ranged from
      robust growth when dissociated cells were seeded on to slice cultures of normal
      target tissue, to apparently no attachment or growth when cells were seeded on to
      non-target tissue. This combined technique appears to be a useful method for
      studies of specificity of cell attachment and patterns of neurite outgrowth.

PMID- 9276491
TI  - Temporal pattern of AP-1 DNA-binding activity in the rat hippocampus following a
      kindled seizure.
AB  - DNA binding by transcripton factor AP-1 was enhanced remarkably following
      kindling stimulation in rat amygdala. Maximum increase occurred 2 h after
      stimulation with return to baseline within 24 h. Supershift and western analyses
      revealed that 38,000 mol. wt Fos-related antigen and JunD were the main
      components of the evoked AP-1 complexes at the time their induction reached
      maximum. AP-1 induction 2 h after the last kindling stimulation was more
      prominent in samples from previously kindled rats than in those from non-kindled
      rats. This study sought to establish the role of AP-1 in plastic changes of the
      hippocampus associated with kindling. Male Sprague-Dawley rats were kindled from
      the left amygdala until they exhibited Racine15 class 5 generalized seizures.
      Nuclear proteins were extracted from dorsal hippocampi obtained from 0 to 24 h
      after final stimulations. From these, we evaluated the temporal pattern of DNA
      binding by AP-1 using a gel mobility-shift assay with a 32P-labelled AP-1 probe.
      Supershift and western analyses were added to investigate components of the
      seizure-evoked AP-1 complexes. Our results suggest that the basal level of AP-1
      complexes is not associated with the seizure susceptibility in kindling. However,
      development of kindling appears to facilitate stimulus-evoked AP-1 induction,
      probably via plastic changes in the central nervous system. AP-1 may mediate such
      changes by regulating expression of certain genes.

PMID- 9276492
TI  - Chronic glucocorticoid administration as well as repeated stress affects the
      subsequent acute immobilization stress-induced expression of immediate early
      genes but not that of NGFI-A.
AB  - We reported that repeated immobilization for six days attenuates the subsequent
      acute immobilization stress-induced expression of the immediate early genes c
      fos, fos B, jun B and nerve growth factor-induced gene-B (NGFI-B), but not of
      NGFI-A, in the rat paraventricular hypothalamic nucleus. In this study, we
      confirmed these findings by means of a time-course study, and further
      investigated whether the elevated plasma basal glucocorticoid level induced by
      repeated stress underlies the attenuated response of immediate early genes and
      the preserved reactivity of NGFI-A. Rats implanted with 100, 200 or 400 mg
      corticosterone or placebo pellets (control), were immobilized for 1 h and
      decapitated seven days later. In control rats acute immobilization induced c-fos,
      fos B, jun B, NGFI-A and NGFI-B messenger RNA in the paraventricular hypothalamic
      nucleus, whereas all of them except NGFI-A, were significantly reduced in rats
      given 200 and 400 mg corticosterone implants. The similarity of the results from
      the two procedures suggests that glucocorticoid is involved in regulating
      immediate early genes in the paraventricular hypothalamic nucleus under repeated
      stress and that the NGFI-A gene is not regulated by this mechanism. However, the
      plasma basal corticosterone level in repeatedly stressed rats was lower than that
      of rats implanted with 100 mg corticosterone, suggesting that a repetitive stress
      induced corticosterone surge also contributes to this mechanism.

PMID- 9276493
TI  - The morphological and chemical characteristics of striatal neurons immunoreactive
      for the alpha1-subunit of the GABA(A) receptor in the rat.
AB  - The distribution, morphology and chemical characteristics of neurons
      immunoreactive for the alpha1-subunit of the GABA(A) receptor in the striatum of
      the basal ganglia in the rat brain were investigated at the light, confocal and
      electron microscope levels using single, double and triple immunohistochemical
      labelling techniques. The results showed that alpha1-subunit immunoreactive
      neurons were sparsely distributed throughout the rat striatum. Double and triple
      labelling results showed that all the alpha1-subunit-immunoreactive neurons were
      positive for glutamate decarboxylase and immunoreactive for the beta2,3 and
      gamma2 subunits of the GABA(A) receptor. Three types of alpha1-subunit
      immunoreactive neurons were identified in the striatum on the basis of cellular
      morphology and chemical characteristics. The most numerous alpha1-subunit
      immunoreactive neurons were medium-sized, aspiny neurons with a widely branching
      dendritic tree. They were parvalbumin-negative and were located mainly in the
      dorsolateral regions of the striatum. Electron microscopy showed that these
      neurons had an indented nuclear membrane, typical of striatal interneurons, and
      were surrounded by small numbers of axon terminals which established alpha1
      subunit-immunoreactive synaptic contacts with the soma and dendrites. These cells
      were classified as type 1 alpha1-subunit-immunoreactive neurons and comprised 75%
      of the total population of alpha1-subunit-immunoreactive neurons in the striatum.
      The remaining alpha1-subunit-immunoreactive neurons comprised of a heterogeneous
      population of large-sized neurons localized in the ventral and medial regions of
      the striatum. The most numerous large-sized cells were parvalbumin-negative, had
      two to three relatively short branching dendrites and were designated type 2
      alpha1-subunit-immunoreactive neurons. Electron microscopy showed that the type 2
      neurons were characterized by a highly convoluted nuclear membrane and were
      sparsely covered with small axon terminals. The type 2 neurons comprised 20% of
      the total population of alpha1-subunit-immunoreactive neurons. The remaining
      large-sized alpha1-immunoreactive cells were designated type 3 cells; they were
      positive for parvalbumin and were distinguished by long branching dendrites
      extending dorsally for 600-800 microm into the striatum. These neurons comprised
      5% of the total population of alpha1-subunit-immunoreactive neurons and were
      surrounded by enkephalin-immunoreactive terminals. Electron microscopy showed
      that the alpha1-subunit type 3 neurons had an indented nuclear membrane and were
      densely covered with small axon terminals which established alpha1-subunit
      immunoreactive symmetrical synaptic contacts with the soma and dendrites. These
      results provide a detailed characterization of the distribution, morphology and
      chemical characteristics of the alpha1-subunit-immunoreactive neurons in the rat
      striatum and suggest that the type 1 and type 2 neurons comprise of separate
      populations of striatal interneurons while the type 3 neurons may represent the
      large striatonigral projection neurons described by Bolam et al. [Bolam J. P.,
      Somogyi P., Totterdell S. and Smith A. D. (1981) Neuroscience 6, 2141-2157.].

PMID- 9276494
TI  - The parafascicular thalamic nucleus modulates messenger RNA encoding glutamate
      decarboxylase 67 in rat striatum.
AB  - We investigated whether the parafascicular thalamostriatal pathway, one of the
      major excitatory inputs to the striatum, regulates the expression in rat striatum
      of messenger RNA encoding two isoforms of glutamate decarboxylase (mol. wt
      67,000: glutamate decarboxylase 67 and mol. wt 65,000: glutamate decarboxylase
      65). Acute (one day) and chronic (14 days) electrolytic lesions of the
      parafascicular nucleus resulted in 58% and 23% decreases in glutamate
      decarboxylase 67 messenger RNA expression, respectively, as determined by
      northern blot analysis. Glutamate decarboxylase 65 messenger RNA was not modified
      by either lesion. Sections of sham- and acute-lesioned striata were processed for
      in situ hybridization histochemistry at the single cell level with an RNA probe
      for glutamate decarboxylase 67. Labelling of glutamate decarboxylase 67 messenger
      RNA was decreased in both types of cells known to be present in the striatum,
      i.e. the lightly and the very densely-labelled neurons. The frequency
      distribution of glutamate decarboxylase 67 labelling per neuron in the lesioned
      striata, in fact, was shifted to the left and its median was lower than in the
      sham-lesioned striata. In view of the excitatory nature of the thalamostriatal
      pathway, we examined the subtype of glutamate receptors modulating the glutamate
      decarboxylase 67 gene expression. The N-methyl-D-aspartate-type receptor
      antagonist, dizocilpine, at 0.1-0.5 mg/kg i.p., produced a marked and persistent
      reduction in striatal glutamate decarboxylase 67 messenger RNA. The non-N-methyl
      D-aspartate receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione (12 nmol/side,
      i.c.v.) had no such effect. The results provide evidence that excitatory
      thalamostriatal afferents selectively modulate the gene expression of glutamate
      decarboxylase 67, probably through the N-methyl-D-aspartate subtype of glutamate
      receptors.

PMID- 9276496
TI  - Activity changes of the cat paraventricular hypothalamus during phasic
      respiratory events.
AB  - We monitored the spatiotemporal organization of cellular activity in the medial
      paraventricular hypothalamus during spontaneously-occurring periods of increased
      inspiratory effort followed by prolonged respiratory pauses (sigh/apnea) in the
      freely-behaving cat. Paraventricular hypothalamic activity was assayed by video
      images of light captured with a stereotaxically-placed fibre optic probe.
      Respiratory activity was measured through electromyographic wire electrodes
      placed in the diaphragm. Sigh/apnea events appeared in all behavioural states,
      and especially during quiet sleep. Overall paraventricular hypothalamic activity
      declined transiently, with the onset of decline coinciding with the beginning of
      the sigh inspiratory effort, reached a nadir at apnea onset 4.4+0.5 s from the
      beginning of the sigh, increased during the course of the apnea, and subsequently
      rebounded above baseline to peak at 10.9+2.5 s after sigh onset. Scattered, small
      areas of the imaged region were activated or depressed independently of the
      overall image values. The data suggest that paraventricular hypothalamic activity
      changes dynamically during phasic respiratory events, and may contribute to the
      progression of the sigh/apnea. We speculate that the medial paraventricular
      hypothalamus influences breathing patterns through projections to parabrachial
      respiratory phase-shift regions, and that longer-latency influences may also be
      exerted indirectly through blood pressure effects from paraventricular
      hypothalamic projections to medullary cardiovascular nuclei. Additionally, the
      paraventricular hypothalamus may convey respiratory influences from other rostral
      structures, such as the hippocampus.

PMID- 9276495
TI  - Reciprocal interaction between glutamate and dopamine in the pars reticulata of
      the rat substantia nigra: a microdialysis study.
AB  - We studied the interactions between glutamate and dopamine in the pars reticulata
      of the substantia nigra by using microdialysis in unanaesthetized rats. Increased
      extracellular levels of glutamate in the pars reticulata were obtained by
      microinjecting the muscarinic agonist carbachol into the ipsilateral subthalamic
      nucleus. The increase of glutamate levels was followed by increments in
      extracellular levels of dopamine and GABA. Increased levels of the three
      neurotransmitters were also observed during the administration of N-methyl-D
      aspartate through the microdialysis probe. The increase in glutamate and GABA
      caused by N-methyl-D-aspartate was blocked by SCH 23390, a selective D1
      antagonist. However, the D1 antagonist did not prevent the increase in dopamine
      levels. The selective D1 agonist SKF 38393, added to the microdialysis probe,
      increased the levels of the three neurotransmitters. However, after the lesion of
      the subthalamic nucleus with kainic acid, SKF 38393 increased only the level of
      GABA but not those of glutamate and dopamine. In addition, the lesion of the
      subthalamic nucleus produced a drastic (80%) fall in the extracellular levels of
      glutamate. These data suggest that glutamate, through N-methyl-d-aspartate
      receptors, stimulates the release of dopamine from dopaminergic dendrites present
      in the substantia nigra pars reticulata, and that dopamine in turn stimulates the
      release of glutamate and GABA. Both effects are mediated by D1 dopamine receptors
      present on subthalamonigral and striatonigral axon terminals, respectively.

PMID- 9276497
TI  - Involvement of nitric oxide and serotonin in modulation of antinociception and
      pressor responses evoked by stimulation in the dorsolateral region of the
      periaqueductal gray matter in the rat.
AB  - In rats anaesthetized with alphaxalone/alphadolone, electrical stimulation in the
      periaqueductal gray matter in the region lying lateral and dorsolateral to the
      aqueduct produced a pressor response and an increase in the latency of the tail
      flick response to noxious heat applied to the tail. The antinociception and the
      pressor response were significantly attenuated following microinjection of 15
      nmol 5-hydroxytryptamine at the site of stimulation in the periaqueductal gray
      matter. Microinjection of an equal volume of 165 mM saline had no effect. The
      inhibitory effects of 5-hydroxytryptamine were blocked by prior
      intracerebroventricular administration of 100 microg of the nitric oxide synthase
      inhibitor L-nitroarginine methyl ester. Neither 5-hydroxytryptamine or L
      nitroarginine methyl ester had any effect on resting arterial pressure or on the
      baseline latency of the tail flick reflex. It is suggested that the inhibitory
      effects of 5-hydroxytryptamine in the dorsolateral periaqueductal gray matter are
      normally dependent on the functional integrity of local nitric oxide synthase
      containing interneurons. Nitric oxide may act in association with 5
      hydroxytryptamine to control the excitability of the aversive system in the
      midbrain.

PMID- 9276498
TI  - Discrete subregions of the rat midbrain periaqueductal gray project to nucleus
      ambiguus and the periambigual region.
AB  - We investigated the organization of projections from the rat midbrain
      periaqueductal gray to nucleus ambiguus and the periambigual region using
      retrograde and anterograde tract tracing techniques. Retrograde tracing results
      revealed that neurons that project to nucleus ambiguus arise from three discrete,
      longitudinally organized columns of neurons located in the supraoculomotor
      central gray, lateral and ventrolateral periaqueductal gray. Anterograde tracing
      studies demonstrated that projections from these three columns of periaqueductal
      gray neurons terminate with topographic specificity in nucleus ambiguus and the
      periambigual region. Double-labelling studies demonstrated that periaqueductal
      gray neurons terminate in close contiguity to cholinergic neurons in the compact,
      semicompact, loose and external formations of nucleus ambiguus. The present
      results suggest that projections from periaqueductal gray to nucleus ambiguus may
      mediate, in part, certain cardiovascular adjustments and vocalizations produced
      by stimulation of periaqueductal gray.

PMID- 9276499
TI  - Punctate appearance of dopamine-beta-hydroxylase on the chromaffin cell surface
      reflects the fusion of individual chromaffin granules upon exocytosis.
AB  - A secretion from cultured bovine chromaffin cells was stimulated to examine the
      pattern of exocytotic fusion on the plasma membrane. Confocal microscopy revealed
      that dopamine-beta-hydroxylase immunofluorescence in intact cells stimulated for
      20s with the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium was almost
      entirely punctate and evenly distributed on the cell surface. The basis for the
      fine, punctate appearance of dopamine-beta-hydroxylase was investigated. Dopamine
      beta-hydroxylase presentation on the surface of permeabilized cells stimulated
      with 1-30 microM Ca2+ was punctate and similar to that on the plasma membrane of
      intact cells. The fluorescence intensities of both surface dopamine-beta
      hydroxylase sites and internal chromaffin granules were estimated by computerized
      digital image analysis. The surface area of punctate surface dopamine-beta
      hydroxylase (0.218 +/- 0.013 microm2, mean +/- S.E.M.) is similar to the surface
      area of a 0.28 microm diameter chromaffin granule (0.25 microm2). The average
      fluorescence intensity integrated over the area of the surface spots was 25-30%
      of the average chromaffin granule intensity, a fraction that is similar to the
      published values of 40-50% of the dopamine-beta-hydroxylase in the chromaffin
      granule being membrane bound. The surface density of the spots is consistent with
      the number of granules undergoing exocytosis. The spots do not tend to be
      clumped. The key conclusions from this work are that each individual punctate
      site of dopamine-beta-hydroxylase represents the fusion of a single chromaffin
      granule and that the distribution of dopamine-beta-hydroxylase spots over the
      cell surface is extensive and random, suggesting that each individual granule
      associates with its own release site.

PMID- 9276500
TI  - Exocytotic release from neuronal cell bodies, dendrites and nerve terminals in
      sympathetic ganglia of the rat, and its differential regulation.
AB  - Stimulant-induced exocytosis has been demonstrated in sympathetic ganglia of the
      rat by in vitro incubation of excised ganglia in the presence of tannic acid,
      which stabilizes vesicle cores after their exocytotic release. Sites of
      exocytosis were observed along non-synaptic regions of the surfaces of neuron
      somata and dendrites, including regions of dendrosomatic and dendrodendritic
      apposition, as well as along the surfaces of nerve terminals About half the
      exocytoses associated with nerve terminals were parasynaptic or synaptic, and
      these appeared mostly to arise from the presynaptic terminal, but occasionally
      from the postsynaptic element. The results demonstrated that the neurons of
      sympathetic ganglia release materials intraganglionically in response to
      stimulation, that release from different parts of the neuron is subject to
      independent regulation, at least via cholinergic receptors, and that release is
      partly diffuse, potentially mediating autocrine or paracrine effects, and partly
      targeted toward other neurons, but that the latter mode is not necessarily, and
      not evidently, synaptic. Specifically, exocytosis from all locations increased
      significantly during incubation in modified Krebs' solution containing 56 nm
      potassium. Observation of the effects of cholinergic agonists (nicotine,
      carbachol, oxotremorine) and antagonists (atropine, AF-DX 116) showed that
      nicotinic and muscarinic excitation each, independently, increased the incidence
      of exocytosis from somata and dendrites. Exocytosis from nerve endings was not
      altered by nicotine, but was enhanced or, at high initial rates of exocytosis,
      decreased, by muscarinic stimulation. Evidence was obtained for muscarinic auto
      inhibition of exocytosis from nerve terminals, occurring under basal incubation
      conditions, and for a muscarinic excitatory component of somatic exocytosis,
      elicitable by endogenous acetylcholine. The M2-selective muscarinic antagonist AF
      DX 116 was found to modify the exocytotic response of the dendrites to
      oxotremorine, widening the range of its variation; this effect is consistent with
      recent evidence for the presence of M2-like muscarinic binding sites, in addition
      to M1-like binding, upon these dendrites [Ramcharan E. J. and Matthews M. R.
      (1996) Neuroscience 71, 797-832]. Over all conditions, disproportionately more
      sites of somatic and dendritic exocytosis were found to be located in regions of
      dendrosomatic and dendrodendritic apposition than would be expected from the
      relative extent of the neuronal surface occupied by these relationships. Such
      mechanisms of intraganglionic release may be expected to contribute to the
      regulation and integration of the behaviour of the various functionally
      distinctive populations of neurons in these ganglia, by autocrine, paracrine, and
      focal, neuroneuronal, routes of action. Similar phenomena of exocytotic soma
      dendritic release might prove to subserve integrative neuroneuronal interactions
      more widely throughout the nervous system.

PMID- 9276501
TI  - Gene transfer into sympathetic preganglionic neurons in vivo using a non
      replicating thymidine kinase-deficient herpes simplex virus type 1.
AB  - The suitability of non-replicating thymidine kinase deficient herpes simplex
      virus type 1 expressing bacterial beta-galactosidase (tk-lacZ HSV-1) as a
      transfer vehicle into sympathetic preganglionic neurons in vivo was assessed.
      Many sympathoadrenal preganglionic neurons (451 +/- 105) with normal morphology
      were identified using beta-galactosidase histochemistry two days after
      inoculation of tk-lacZ HSV-1 into the adrenal gland of hamsters. Beta
      galactosidase activity co-localized with nicotinamide adenine dinucleotide
      phosphate-diaphorase-positive sympathetic preganglionic neurons in the nucleus
      intermediolateralus, pars principalis. The maximal number of beta-galactosidase
      expressing neurons was found two days post-inoculation but this number dropped
      dramatically after this time. An inflammatory infiltrate was abundant around
      infected neurons and in the white matter at five days and infected neurons
      appeared morphologically abnormal. At 26 days, the infiltrate was still present
      but no infected sympathoadrenal preganglionic neurons were detected.
      Approximately 25% fewer nicotinamide adenine dinucleotide phosphate-diaphorase
      positive neurons in the nucleus intermediolateralis, pars principalis were
      counted ipsilaterally than contralaterally in animals infected for 14, 21 or 26
      days with tk-lacZ HSV-1, compared to the 3% difference in animals mock-infected
      for 26 days. Approximately 33% of the estimated number of sympathoadrenal
      preganglionic neurons infected with tk-lacZ HSV-1 at five days were apoptotic or
      necrotic. About 60% of neurons infected with tk-lacZ HSV-1 at two days no longer
      expressed nicotinamide adenine dinucleotide phosphate-diaphorase at 14-26 days.
      In conclusion, the non-replicating thymidine kinase deficient HSV-1 was
      efficiently retrogradely transported from the adrenal gland to infect
      sympathoadrenal preganglionic neurons. These gene transfer experiments using tk
      lacZ HSV-1 suggest that foreign gene expression in sympathetic preganglionic
      neurons in vivo may be maximal two days after inoculation when beta-galactosidase
      was expressed in the greatest number of sympathetic preganglionic neurons. After
      two days, fewer neurons expressed beta-galactosidase and the presence of tk-lacZ
      HSV-1 appeared to be altering protein expression in sympathetic preganglionic
      neurons and/or leading to the demise of the infected neuron.

PMID- 9276502
TI  - Characterization of myenteric interneurons with somatostatin immunoreactivity in
      the guinea-pig small intestine.
AB  - The projections, connections, morphology and electrophysiological features of the
      myenteric interneurons with somatostatin immunoreactivity in the guinea-pig small
      intestine have been established using retrograde tracing, immunohistochemistry,
      confocal microscopy and intracellular recording. After application of the
      fluorescent dye, 1,1'-didodecyl-3,3,3',3'-tetramethyl indocarbocyanine
      perchlorate (DiI), to the myenteric plexus, up to 900 nerve cell bodies were
      labelled in each preparation. Somatostatin-immunoreactive neurons accounted for
      13% of all retrogradely labelled cells and were located up to 70 mm orally. When
      DiI was applied to the submucous ganglia, many myenteric neurons were labelled
      and 8% of all retrogradely labelled cells were somatostatin immunoreactive and
      were located up to 60 mm oral to the DiI application sites. These neurons had
      ovoid cell bodies, a single axon, several long filamentous dendrites and received
      close contacts from 40-200 somatostatin-immunoreactive varicosities.
      Intracellular recordings revealed that these cells had features of both S (i.e.
      with Synaptic inputs) and AH (i.e. neurons with After Hyperpolarization) cells,
      receiving fast excitatory synaptic inputs, having characteristic "sag" in their
      response to hyperpolarizing current pulses and sometimes a long
      afterhyperpolarization following soma action potentials. It is concluded that
      somatostatin-immunoreactive neurons have distinct electrophysiological features
      and form very long anally directed interneuronal chains that connect with both
      myenteric and submucous neurons.

PMID- 9276503
TI  - Ultrastructural relationships of spinal primary afferent fibres with neuronal and
      non-neuronal cells in the myenteric plexus of the cat oesophago-gastric junction.
AB  - Spinal primary afferent fibres innervating the myenteric area in the oesophago
      gastric junction of the cat were selectively labelled by anterogradely
      transported cholera toxin B subunit-horseradish peroxidase conjugate injected
      into thoracic dorsal root ganglia. The ultrastructure of these labelled primary
      afferent fibres was studied in order to determine whether they display close
      relationships with specific cell types in the myenteric plexus. Horseradish
      peroxidase was revealed with tetramethylbenzidine stabilized with ammonium
      heptamolybdate or with the tetramethylbenzidine/tungstate reaction in order to
      visualize the cytoplasmic organelles and the axolemma, respectively. The labelled
      primary afferent fibres were unmyelinated. Two kinds of profiles of labelled
      fibres containing vesicles and mitochondrial accumulations were found: (i) fibres
      running in myenteric connectives in isolated nerve bundles, and (ii) fibres
      within the myenteric ganglia. The first kind had small areas of axolemma with no
      glial cell covering, whereas the second kind had little or no glial cell covering
      (termed naked primary afferent fibres). In addition, labelled fibres containing
      few vesicles and mitochondria and running in nerve bundles surrounded by
      perineurium were numerous. Within the myenteric ganglia, naked primary afferent
      fibres contacted myenteric neurons. The contacts were mainly axosomatic. No
      synaptic specializations were distinguished. In the interganglionic area, some
      labelled fibres terminated close to blood vessels. The intraganglionic naked
      primary afferent fibres are suggested to be mechanoreceptors. Their exposed
      axolemma might allow both mechanotransduction and release of neurotransmitters
      which could act on myenteric neurons. Because they are protected by their glial
      cell sheath and by bundles of collagen fibrils, interganglionic primary afferent
      fibres are likely to be less exposed to deformation.

PMID- 9276504
TI  - Formalin-induced nociceptive behavior and edema: involvement of multiple
      peripheral 5-hydroxytryptamine receptor subtypes.
AB  - The role of 5-hydroxytryptamine and its receptor subtypes in the development of
      acute inflammation was investigated using the rat paw formalin test as a model
      for pain (measured by flinching behavior) and edema formation (measured by
      plethysmometry). The role of endogenously released 5-hydroxytryptamine was
      assessed using 5-hydroxytryptamine receptor subtype-selective antagonists co
      injected with 2.5% formalin, while the receptor subtypes involved in the
      inflammatory process were further defined by co-injection of 5-hydroxytryptamine
      or 5-hydroxytryptamine receptor subtype-selective agonists with 0.5% formalin in
      anticipation of an augmented response. When co-administered with 2.5% formalin,
      propranolol, tropisetron or GR113808A, but not ketanserin, effectively blocked
      nociceptive behavior. In the presence of 0.5% formalin, 5-carboxamidotryptamine,
      1-(m-chlorophenyl) biguanide or 5-methoxytryptamine, but not (+/-)-1-4-(4-iodo
      2,5-dimethoxyphenyl)-2-aminopropane, augmented the flinching response. These data
      suggest involvement of 5-hydroxytryptamine1, 5-hydroxytryptamine3 and 5
      hydroxytryptamine4 receptors in peripheral nociception. There may be some
      dissociation of nociception and edema formation, since no single 5
      hydroxytryptamine receptor antagonist inhibited edema formation with 2.5%
      formalin; however, with 0.5% formalin, edema formation was enhanced by co
      administration of 5-hydroxytryptamine, 5-carboxamidotryptamine, (+/-)-1-4-(4-iodo
      2,5-dimethoxyphenyl)-2-aminopropane or 5-methoxytryptamine, but not 1-(m
      chlorophenyl) biguanide. These data suggest involvement of 5-hydroxytryptamine1,
      5-hydroxytryptamine2 and possibly 5-hydroxytryptamine4 receptors in edema
      formation. These results confirm the involvement of 5-hydroxytryptamine1 and 5
      hydroxytryptamine3 receptor subtypes in peripheral nociception associated with
      acute inflammation and further suggest an involvement of the more recently
      characterized 5-hydroxytryptamine4 receptor in this process. There appears to be
      a dissociation in 5-hydroxytryptamine receptors involved in peripheral
      nociception and edema formation.

PMID- 9276506
TI  - The behaviour of mitochondria and cell integration during somatic hybridisation
      of sister blastomeres of the 2-cell mouse embryo.
AB  - The capacity of sister blastomeres of mouse embryos for induced fusion changed
      during the 2-cell stage. It was at low level (24%) at the early 2-cell stage,
      increased and reached 98.5% at the middle 2-cell stage and fell sharply to 31% at
      the late 2-cell stage. At the time corresponding to the G2/M-phase of the cell
      cycle the blastomeres fused in only 8% of cases. Vital staining of 2-cell embryos
      by rhodamine 123 showed that the mitochondria were dispersed throughout the
      cytoplasm with a ring-like (around the nucleus) or spot-like (over the metaphase
      plate) concentration in the centre of each blastomere. At the periphery of
      blastomeres the mitochondrial content was low. The behaviour of the mitochondria
      reflected the subsequent events of structural and functional integration of the
      sister blastomeres under induced fusion: a discernible boundary between partners
      during 30 min after electrofusion or 1 h after fusion with polyethylene glycol;
      movement of the two 'rings' to the centre of the blastomere fusion products (BFP)
      to form one large bright 'spot' over the common metaphase plate; mitochondria
      outlining the shape of the spindle and connection between sister blastomeres
      until completion of the first mitosis of BFP. The data obtained suggest that
      fusion of the blastomeres does not lead to extensive changes in the hybrid
      cytoplasm and integration of nuclear material is taking place only at metaphase
      stage. Cytogenetic examination of BFP at the 2-cell stage confirmed
      reconstruction of the tetraploid embryos and found that sister blastomeres of
      such embryos could asynchronously enter the next cleavage division similarly to
      normal diploid 2-cell embryos.

PMID- 9276505
TI  - Expression of the genes for alpha-type and beta-type calcitonin gene-related
      peptide during postnatal rat brain development.
AB  - In this study we have analysed the expression of the genes for both alpha-type
      and beta-type calcitonin gene-related peptide (CGRP) during postnatal development
      of the rat brain and compared it with the expression of CGRP-like
      immunoreactivity. At birth both alpha-type and beta-type CGRP messenger RNA were
      present in the parabrachial nucleus, inferior olive and motor nuclei (except for
      abducens nucleus), and only alpha-type CGRP messenger RNA in some posterior
      thalamic nuclei. As development advanced, new nuclei started to express either
      only alpha-CGRP gene (superior olive, parabigeminal, sagulum, and some
      hypothalamic and cranial thalamic nuclei) or both genes (abducens nucleus). In
      the inferior olive both genes were transiently expressed. Beta-CGRP messenger RNA
      disappeared by postnatal day 10 and alpha-CGRP messenger RNA by postnatal day 20.
      During the whole postnatal development beta-CGRP gene expression predominated
      over that of alpha-CGRP in the trigeminal and eye motor nuclei, while in the
      remainder nuclei alpha-CGRP messenger RNA was either the predominant isoform or
      the sole one. CGRP-like immunoreactivity, which does not distinguish between
      alpha-type and beta-type CGRP, was detected in those nuclei containing either
      alpha-CGRP messenger RNA or beta-CGRP messenger RNA. However, no CGRP messenger
      RNA was detected in areas such as superior colliculus, lateral pontine nucleus,
      pars reticulata of the substantia nigra, perifornical area, or zona incerta in
      which CGRP-like immunoreactivity was prominent. CGRP-like immunoreactivity, but
      not CGRP messenger RNA, was also transiently detected by postnatal day 5 in some
      cells of the globus pallidus. In the adult brain, the levels of alpha- and beta
      CGRP messenger RNA as well as those of CGRP-like immunoreactivity were
      considerably reduced. This fact, similar to that of other growth- and development
      associated factors, suggests a role for CGRP as a neuron-derived neurotrophic
      factor. The transient expression in neurons of the inferior olive, matching the
      period when climbing fibres and cerebellar cortex are developing, seems to
      support such an idea. The results of this study show that those nuclei expressing
      beta-CGRP gene also express alpha-CGRP gene. However, there are a number of
      nuclei that only express alpha-CGRP gene. On the other hand, CGRP-like
      immunoreactivity is detected in some nuclei which express no CGRP messenger RNA.
      It suggests that such nuclei express any CGRP-related protein (identified by the
      antibodies against CGRP) or, if they really contain CGRP protein, this is
      produced from undetectable amounts (using our in situ hybridization
      histochemistry procedure) of CGRP messenger RNA or it comes from other nuclei
      that connect with them in which CGRP protein is synthesized and then transferred.

PMID- 9276507
TI  - Strain difference in the timing of meiosis resumption in mouse oocytes:
      involvement of a cytoplasmic factor(s) acting presumably upstream of the
      dephosphorylation of p34cdc2 kinase.
AB  - Oocytes from eight inbred strains of mice were screened for the timing of
      germinal vesicle breakdown (GVB) in vitro. This characteristic varied between
      strains, reaching most extreme values in oocytes from AKR and BALB/c mice (3.1
      and 1.6 h after release from dibutyryl cAMP block, respectively; p < 0.0001). The
      difference between AKR and BALB/c mice was confirmed in experiments in which GVB
      was induced in vivo by stimulation with exogenous gonadotrophins. Analysis of the
      rate of GVB in hybrids obtained after fusion of nuclear and cytoplasmic fragments
      of oocytes from both strains suggests that the factor responsible for the
      difference between AKR and BALB/c mice is located in the cytoplasm of the
      prophase oocytes. Finally, in oocytes from both strains stimulated to resume
      meiotic maturation with okadaic acid, an inhibitor of protein phosphatases types
      1 and 2A, the rate of GVB was the same (2.2h and 2.3h for AKR and BALB/c,
      respectively; p=0.48). This suggests that the difference between strains is not
      related to the amount or quality of the pre-MPF (Maturation Promoting Factor)
      stored in the prophase oocyte, but to the factor(s) acting upstream of the
      dephosphorylation of p34cdc2 kinase in the pathway leading to pre-MPF activation.

PMID- 9276508
TI  - Beneficial effect of medium with high concentration serum for direct sperm
      injection into mouse oocytes using a conventional pipette.
AB  - Although the piezo-electrically driven pipette is much more effective than a
      conventional pipette for direct sperm injection into mouse oocytes, the piezo
      pipette driving unit is expensive and may not be readily accessible to most basic
      science laboratories. We report here that the inefficiency of the conventional
      pipette can be improved by performing the operation in a medium with high serum
      concentration.

PMID- 9276509
TI  - Chlortetracycline fluorescence patterns and in vitro fertilisation of frozen
      thawed boar spermatozoa incubated under various bicarbonate concentrations.
AB  - Porcine oocyte-cumulus complexes were cultured in bovine serum albumin (BSA)-free
      North Carolina State University (NCSU) 23 medium containing porcine follicular
      fluid (10%), cysteine (0.1 mg/ml) and hormonal supplements (eCG and hCG: 10 IU/ml
      each) for 22h. They were then cultured in the same medium but without hormonal
      supplements for an additional 22 h. After culture, cumulus cells were removed and
      oocytes were co-incubated with frozen-thawed ejaculated boar spermatozoa in
      tissue culture medium (TCM) 199 containing caffeine (5 mM), fetal calf serum
      (FCS; 10%) and varying concentrations (26-56 mM) of NaHCO3 for 9 h (experiment
      1). In experiment 2, chlortetracycline (CTC) was used to assess the functional
      state of spermatozoa incubated under different NaHCO3 concentrations. Experiment
      3 examined the effect of FCS (1% and 10%) and NaHCO3 (26 and 46 mM) on
      fertilisation parameters. Compared with 26 mM, penetration rate was significantly
      higher (p < 0.05) at 36-56 mM NaHCO3. Polyspermy showed a similar pattern
      although no difference was observed between 26 and 36 mM. At 46 mM NaHCO3, the
      mean number of spermatozoa (MNS) penetrated per oocyte increased significantly (p
      < 0.05). A significantly higher proportion of spermatozoa were capacitated and
      acrosome reacted at 46 and 56 mM NaHCO3, respectively. The fertilisation medium
      containing 46 mM NaHCO3 and 1% FCS showed a higher penetration rate (84%) with a
      relatively low incidence of polyspermy (39%). The results indicate that NaHCO3
      stimulates capacitation and/or the acrosome reaction of boar spermatozoa in a
      dose-dependent manner and thus affects fertilisation parameters.

PMID- 9276510
TI  - Caffeine overrides the S-phase cell cycle block in sea urchin embryos.
AB  - During the early mitotic cell cycles of the sea urchin embryo, the cell
      oscillates between S-phase and M-phase. In the presence of aphidicolin, a DNA
      synthesis inhibitor, a checkpoint control blocks the activation of the p34cdc2
      protein kinase, by keeping it in the inactive, tyrosine phosphorylated form, and
      the embryos do not enter mitosis. Caffeine has been shown to bypass the G2/M
      phase checkpoint in mammalian cells and in cycling Xenopus extracts and to induce
      mitosis despite the presence of damaged or unreplicated DNA. In this study we
      show that caffeine also induces mitosis and cell division in sea urchin embryos,
      in the presence of unreplicated DNA, by stimulating the tyrosine
      dephosphorylation of p34cdc2 and switching on its protein kinase activity. We
      also show that the caffeine-induced activation of the p34cdc2 protein kinase is
      not mediated by either of the two second messengers, calcium and cAMP, or by
      inhibition of the p34cdc2 tyrosine kinase. Thus, none of the mechanisms proposed
      for caffeine's action can explain how it overrides the S-phase checkpoint in the
      early cell cycles of the sea urchin embryo.

PMID- 9276511
TI  - Primordial germ cells and oocytes of Branchiostoma virginiae (Cephalochordata,
      Acrania) are flagellated epithelial cells: relationship between epithelial and
      primary egg polarity.
AB  - Primordial germ cells (PGCs) are described from the gonad of c. 2 cm juvenile
      Branchiostoma virginiae; early oocytes (c. 10 microm) and enlarging,
      previtellogenic oocytes (c. 35 microm) are described from the ovary of c. 5 cm
      adults. The germinal epithelium of the juvenile gonad and adult ovary is composed
      of both germinal and somatic cells. In the juvenile, somatic cells retain contact
      with the basal lamina of the germinal epithelium though their perikarya may be
      displaced towards the lumen; the germinal epithelium is, therefore, a simple but
      pseudostratified epithelium. In the adult ovary, somatic cells may lose contact
      with the basal lamina and the epithelium appears to become stratified. PGCs and
      oocytes are identified as germ cells by the presence of nuage. PGCs and oocytes
      are polarised epithelial cells. They rest on a basal lamina, extend apically
      towards a lumen, form adhering junctions with neighbouring cells, and exhibit
      apical-basal polarity. PGCs and early oocytes have an apical flagellum with an
      associated basal body, accessory centriole, and one or more striated rootlet
      fibres. The flagellum is surrounded by a collar of microvilli. Once oocytes begin
      to enlarge and bulge basally into the connective tissue layer, the flagellum is
      lost, but the basal bodies and ciliary rootlets are present at the apex of 35
      microm oocytes. Similarities of the oogenic pattern in cephalochordates and
      echinoderms indicate that the establishment of egg polarity in deuterostomes is
      influenced by the polarity of the germinal epithelium.

PMID- 9276512
TI  - Effect of inhibitors of DNA replication on early zebrafish embryos: evidence for
      coordinate activation of multiple intrinsic cell-cycle checkpoints at the mid
      blastula transition.
AB  - We address the developmental activation, in the zebrafish embryo, of intrinsic
      cell-cycle checkpoints which monitor the DNA replication process and progression
      through the cell cycle. Eukaryotic DNA replication is probably carried out by a
      multiprotein complex containing numerous enzymes and accessory factors that act
      in concert to effect processive DNA synthesis (Applegren, N. et al. (1995) J.
      Cell. Biochem. 59, 91-107). We have exposed early zebrafish embryos to three
      chemical agents which are predicted to specifically inhibit the DNA polymerase
      alpha, topoisomerase I and topoisomerase II components of the DNA replication
      complex. We present four findings: (1) Before mid-blastula transition (MBT) an
      inhibition of DNA synthesis does not block cells from attempting to proceed
      through mitosis, implying the lack of functional checkpoints. (2) After MBT, the
      embryo displays two distinct modes of intrinsic checkpoint operation. One mode is
      a rapid and complete stop of cell division, and the other is an 'adaptive'
      response in which the cell cycle continues to operate, perhaps in a 'repair'
      mode, to generate daughter nuclei with few visible defects. (3) The embryo does
      not display a maximal capability for the 'adaptive' response until several hours
      after MBT, which is consistent with a slow transcriptional control mechanism for
      checkpoint activation. (4) The slow activation of checkpoints at MBT provides a
      window of time during which inhibitors of DNA synthesis will induce cytogenetic
      lesions without killing the embryo. This could be useful in the design of a
      deletion-mutagenesis strategy.

PMID- 9276513
TI  - Chromosomes of mouse primary spermatocytes undergo meiotic divisions after
      incorporation into homologous immature oocytes.
AB  - The primary spermatocytes used were male germ cells at prophase I. The present
      study was undertaken to see whether bivalent chromosomes of mouse primary
      spermatocytes can undergo meiotic divisions within maturing oocytes and
      participate in subsequent embryonic development. Primary spermatocytes (pachytene
      to diplotene) freshly collected from the testes of mature males were electrofused
      with immature oocytes shortly before or after germinal vesicle breakdown. After
      culture in MEM-alpha medium for 15 h, most (> 90%) of the oocytes containing
      spermatocyte chromosomes underwent maturation and arrested at metaphase II (MII).
      Among 23 MII oocytes examined, 17 (74%) had one group of chromosomes and one
      polar body, indicating that male chromosomes had intermingled with those of the
      females and completed the first meiotic division. Chromosome analyses of these
      MII oocytes demonstrated their diploidy. The metaphase chromosomes were
      transferred to enucleated MII oocytes freshly recovered from superovulated mice.
      After artificial activation, the reconstructed MII oocytes resumed meiosis and
      developed to the morula/blastocyst stage. However, no pups were born following
      embryo transfer into recipient females. These findings indicate that the
      chromosomes of primary spermatocytes undergo meiotic divisions in maturing
      oocytes and participate in the formation of diploid embryos.

PMID- 9276514
TI  - Transformation of sperm nuclei into metaphase chromosomes in maturing pig oocytes
      penetrated in vitro.
AB  - Cumulus-free pig oocytes at the germinal vesicle (GV) stage were incubated in
      modified Brackett & Oliphant's medium with 5% fetal calf serum and 5mM caffeine
      with or without cryopreserved, ejaculated spermatozoa. When oocytes were
      transferred into modified tissue culture medium (TCM-199B at pH 7.4) supplemented
      with 10 IU/ml eCG, 10 IU/ml hCG and 1 microg/ml oestradiol-17beta after 8 h of
      incubation with spermatozoa and cultured for 0-48 h, 86-99% of oocytes were
      penetrated. Most (95-100%) oocytes penetrated 0-16 h after transfer had
      decondensed sperm chromatin. However, 24 h after transfer 47% and 33% of
      penetrated oocytes contained recondensed sperm chromatin and sperm metaphase
      chromosomes, respectively. The proportion of penetrated oocytes containing sperm
      metaphase chromosomes increased after 36-48 h of transfer (51-65%). The
      transformation of sperm nuclei to metaphase chromosomes was obtained in 75% and
      79% of anaphase I (AI) to telophase I (TI) and metaphase II (MII) oocytes,
      respectively, but only in 38% of metaphase I (MI) oocytes. Moreover, such
      transformation was observed only in 1 of 30 oocytes at the stages of GV breakdown
      to prometaphase I and none of 69 oocytes at the GV stage. The transformation of
      sperm nuclei into metaphase chromosomes was completely inhibited in oocytes
      penetrated by eight or more spermatozoa. Well-developed male and female pronuclei
      were observed in only 3 (4%) of 77 oocytes penetrated 48 h after transfer. The
      proportion of oocytes reaching MII was greatly inhibited by sperm penetration;
      only 18% of penetrated oocytes, but 87% of non-inseminated oocytes, reached MII
      by 48 h after transfer. None of the oocytes penetrated by seven or more
      spermatozoa reached MII. Most (75%) oocytes were inhibited from the transition
      from MI to MII even though they were cultured for 48 h. The present results
      indicate that: (1) the cytoplasm of maturing oocytes possesses an activity for
      transforming sperm nuclei into metaphase chromosomes, (2) immature pig oocytes
      penetrated by spermatozoa can undergo meiotic maturation to MI, and (3) the
      transition of such oocytes from MI to MII is inhibited, suggesting that an
      activity of mitogen-activated protein kinase may be retarded.

PMID- 9276515
TI  - CD1d: outside-in antigen presentation in the intestinal epithelium?

PMID- 9276516
TI  - Comparison of nucleic acid and protein immunization for induction of antibodies
      specific for HIV-1 gp120.
AB  - We have compared the antibody response to HIV-1 gp120 type LAI in mice immunized
      with either a gp120 expression plasmid or with baculovirus-derived recombinant
      gp120 (rgp120) formulated with Freund's complete adjuvant. TiterMax, Alum, Ribi R
      700, AF-A or QuilA. DNA immunization resulted in variable levels of antibody,
      with endpoint titres ranging from 10(4) to 10(5), whereas mice immunized with rgp
      120 mixed with Ribi R-700, AF-A or QuilA produced antibody levels with endpoint
      titres > 10(5). Both types of immunization failed to elicit antibodies able to
      recognize denatured rgp120. The V3 region was immunogenic in animals immunized
      with nucleic acid, whereas only a few animals immunized with recombinant protein
      produced antibodies specific for V3 or other linear epitopes, irrespective of the
      adjuvant used. These data suggest that the immunogenicity of gp120 is dependent
      upon the mode of antigen delivery, and that in vivo expressed gp120 following
      nucleic acid immunization elicits, at least with respect to V3, an antibody
      response which more closely reflects that seen following natural infection in
      man.

PMID- 9276517
TI  - Haemophilus influenzae and Streptococcus pneumoniae induce different
      intracerebral mRNA cytokine patterns during the course of experimental bacterial
      meningitis.
AB  - Using in situ hybridization with radiolabelled oligonucleotide probes, we studied
      the mRNA expression of IL-1beta, IL-4, IL-6, IL-10, IL-12, tumour necrosis factor
      alpha (TNF-alpha), TNF-beta, interferon-gamma (IFN-gamma), and transforming
      growth factor-beta (TGF-beta) in the brain during the lethal course of
      experimental meningitis in a rat model inoculated intracisternally with
      Haemophilus influenzae type b (Hib) or Streptococcus pneumoniae and in uninfected
      control rats inoculated with the same volume of PBS. The production of IL-1beta,
      IL-4, IL-6 and IFN-gamma was also evaluated by immunohistochemistry. In the brain
      of Hib-inoculated rats, there was marked mRNA expression of IL-1beta, IL-6, TNF
      alpha, IL-12 and IFN-gamma. IL-1beta, IL-6 and TNF-alpha were up-regulated
      throughout the observation period at 2, 8 and 18 h post-inoculation (p.i.), with
      similar patterns of induction. The Th1 cytokines IFN-gamma and TNF-beta were up
      regulated within 8 h p.i. IL-10 and TGF-beta were down-regulated at 18 h p.i.,
      while IL-4 was not detected. In contrast, the brain of S. pneumoniae-inoculated
      rats showed lower levels of IL-1beta, IL-6 and TNF-alpha, but higher levels of
      TNF-beta and detectable mRNA expression of IL-4 when compared with Hib-inoculated
      rats. IL-12, IFN-gamma, IL-10 and TGF-beta exhibited similar patterns of
      induction in the brains of Hib- and S. pneumoniae-inoculated rats. At 18 h p.i.,
      immunohistochemistry showed similar patterns of IL-1beta, IL-4, IL-6 and IFN
      gamma as mRNA expression in the brains of Hib- and S. pneumoniae-inoculated rats.
      The differences of cytokine profiles induced by the two bacterial strains may
      imply that different immunomodulating approaches should be considered, depending
      on etiology.

PMID- 9276518
TI  - Regulatory role of exogenous IL-10 in the development of immune response versus
      Cryptococcus neoformans.
AB  - The most important event involved in host defence against Cryptococcus neoformans
      is the development of an adequate cell-mediated immune response. IL-10,
      abundantly produced during AIDS progression, could be a negative factor that
      affects the T cell response through its own immunosuppressive action on antigen
      presenting cells. To determine whether this cytokine affects the course of immune
      response against C. neoformans, we added exogenous IL-10 to cultured Cryptococcus
      laden monocytes plus T lymphocytes. The data from this study confirmed the down
      regulatory effect of exogenous IL-10 on monocytes and expanded the known
      inhibitory role to include an increase of the deleterious effect due to capsular
      material of C. neoformans on (i) lymphoproliferation, (ii) down-regulation of MHC
      class II molecules, (iii) inhibition of IL-2 mRNA expression and protein
      secretion by T lymphocytes. These results indicate that the presence of IL-10 in
      AIDS patients, due to the progression of disease, could represent a pivotal
      problem contributing to augment the pathogenic effect of C. neoformans.

PMID- 9276519
TI  - Effector molecules of the host defence mechanism against Mycobacterium avium
      complex: the evidence showing that reactive oxygen intermediates, reactive
      nitrogen intermediates, and free fatty acids each alone are not decisive in
      expression of macrophage antimicrobial activity against the parasites.
AB  - In this study, we evaluated the roles of reactive oxygen intermediates (ROI),
      reactive nitrogen intermediates (RNI), and free fatty acids (FFA) as effectors of
      the macrophage-mediated host defence mechanism against Mycobacterium avium
      complex (MAC). First, M. avium (three strains) and M. intracellulare (two
      strains) were treated with the H2O2-Fe2+-mediated halogenation system, acidified
      NaNO2-derived RNI, or FFA (linolenic acid) in sodium acetate buffer pH 5.5, and
      then counted for the number of residual colony-forming units (CFU) of organisms.
      Although these effectors exerted strong bactericidal activity against the MAC,
      the susceptibility of test organisms markedly varied from strain to strain. There
      was no significant relationship between the degree of resistance of a given MAC
      strain to these effectors and its virulence in mice, indicating that ROI, RNI,
      and FFA each alone are not decisive as the effector components of the host
      defence mechanism against the MAC. Second, the increase in ROI-producing ability
      in murine peritoneal macrophages due to tumour necrosis factor-alpha (TNF-alpha)
      treatment was not accompanied by parallel potentiation of anti-MAC activity of
      the same macrophage population. This excludes the possibility that ROI play a
      central role in macrophage-mediated killing and inhibition of MAC organisms.
      Third, anti-MAC activity of BAM3 macrophage cell line was not significantly
      attenuated by N(G)-monomethyl-L-arginine (NO synthase-inhibitor causing reduction
      of RNI production) or by quinacrine (phospholipase A2-inhibitor causing reduction
      of FFA release), indicating that RNI and FFA each alone do not play crucial roles
      in the expression of macrophage antimicrobial activity against the MAC. The
      present findings suggest important roles of collaborating actions of various
      antimicrobial effectors and/or the participation of other kinds of effectors in
      macrophage-mediated killing and inhibition of MAC organisms.

PMID- 9276520
TI  - Cytokine responses to the native and recombinant forms of the major surface
      glycoprotein of Pneumocystis carinii.
AB  - Pneumocystis carinii is a major opportunistic pathogen and leading cause of
      morbidity in patients with AIDS. The major surface glycoprotein (MSG) of P.
      carinii, represented by a family of related proteins encoded by unique genes, is
      highly immunogenic and contains T cell-protective epitopes. We undertook the
      present study to define the CD4 T helper (Th) response by cytokine secretion to
      native MSG and a recombinant form of the protein, MSG-B. Spleen cells were
      collected from Lewis rats and restimulated with both native MSG and MSG-B. Within
      24 h, the CD4 cells secreted high levels of interferon-gamma (IFN-gamma) in
      response to both types of antigen, indicative of a Th1 response; however, after
      72h of incubation, only the native MSG stimulated secretion of IL-4 (Th2
      response) from the cells. We then investigated whether the presence of IL-4 could
      alter the predominant Th1 phenotype by the CD4 cells in response to MSG and MSG
      B. Cells cultured with native MSG and IL-4 produced low levels of IFN-gamma and
      elevated levels of IL-4. Interestingly, cells incubated with MSG-B and IL-4
      reduced production of IFN-gamma, but were not stimulated to produce increased
      levels of IL-4. The presence of anti-IFN-gamma antibody in the MSG- or MSG-B
      stimulated cultures did not effect the expression of IFN-gamma mRNA, suggesting
      that the generation of Th1 cells in response to MSG or MSG-B was not dependent on
      IFN-gamma. We conclude that native MSG, which contains multiple forms of this
      antigen, and recombinant MSG elicit different cytokine responses in vitro. These
      data are not only important to studies of MSG, but may also be relevant to the
      role of MSG in the immunopathogenesis of P. carinii infection in vivo.

PMID- 9276521
TI  - Cellular requirements for immunomodulatory effects caused by cell wall components
      of Paracoccidioides brasiliensis on antibody production.
AB  - In a previous study, we reported an increase in the number of immunoglobulin
      secreting cells and the augmentation of antibody production (IgM and IgG3)
      against unrelated antigens (sheep erythrocytes or bovine serum albumin (BSA)) in
      mice infected with the fungus Paracoccidioides brasiliensis as well as in mice
      inoculated with its cell wall preparation (CW). The immunomodulatory effect of
      the live fungus and CW preparation was dose-dependent and mainly restricted to
      the i.p. inoculation simultaneously to the BSA challenge by the i.v. route. In
      the present study, we investigated the active component of CW preparation upon
      the phenotype and also the degree of activation of possible target peritoneal
      cells involved in those phenomena. An insoluble polysaccharide fraction (F1
      fraction) mainly composed of beta-glucan and chitin, and the purified beta-glucan
      (BGPb) behaved as CW in the augmentation of early antibody production. The
      peritoneal mononuclear inflammatory cells induced by CW, F1 fraction and BGPb
      were highly positive to alpha-naphthyl esterase staining; released low H2O2;
      expressed high levels of MHC-Ia(d) molecules and produced inflammatory cytokines
      such as tumour necrosis factor-alpha (TNF-alpha) and IL-6. Phenotypic analysis by
      flow cytometry and immunohistochemical techniques of the inflammatory cells
      responding to F1 fraction showed a prevalence of (CD11b/CD18, Mac-1)+ peritoneal
      macrophages. In addition, s.c. inoculation of F1 fraction resulted in the
      formation of nodular, localized and not progressive granulomatous lesions with an
      accumulation of (CD11b/C18)+ macrophages. Adoptive transferred Mac-1 macrophages
      to immunized syngeneic recipient mice were able to cause an increase in anti-BSA
      antibody production. These results suggest that inflammatory (CD11b/CD18)+
      macrophages may be related to immunological disturbances, caused by cell wall
      components of P. brasiliensis.

PMID- 9276522
TI  - Absence of streptococcal protein G (PG)-specific determinant in the Fab region of
      human IgG2.
AB  - It has been previously reported that CH1 Fab protein G-contact site is
      responsible for the widespread recognition of mouse and human IgG Fab by PG. Here
      we present evidence that PG binding to F(ab')2 is restricted, as indicated by the
      lack of reactivity with PG-Sepharose columns of a portion of F(ab')2 fragments
      obtained by pepsin digestion of human IgG from a commercial immunoglobulin
      preparation for intravenous use or purified from sera of two healthy blood donors
      and two patients with polyclonal hypergammaglobulinaemia. Isoelectric focusing
      showed that F(ab')2 fragments that did not bind PG focused in a lower pH range
      compared with those which did. Testing of the Fab fractions with MoAbs to kappa
      and lambda light chains or to gamma1, gamma2 and gamma3-Fab subclass determinants
      showed that gamma2-F(ab')2 were mainly found in the PG non-reactive F(ab')2
      fraction, and that this distribution was not influenced by the L chain isotype.
      These results indicate that the PG-specific binding determinant(s) is not
      expressed in the F(ab')2 region of most human IgG2.

PMID- 9276523
TI  - Expression of lactoferrin on human granulocytes: analysis with polyclonal and
      monoclonal antibodies.
AB  - Lactoferrin (LF), an iron-binding protein present in specific granules of
      neutrophils, is expressed on membrane after granulocyte activation. It may
      represent a target for anti-neutrophil cytoplasmic antibodies (ANCA) in patients
      affected by some immunomediated diseases. We recently produced two MoAbs, AGM
      2.29 and AGM 10.14, that recognize two spatially distant epitopes of human LF. In
      this study we perform a cytometric analysis in order to evaluate the expression
      of LF on the surface of granulocytes obtained from freshly drawn blood or after
      purification, in both the presence and absence of stimuli. Our results
      demonstrate that LF is not constitutively expressed on membrane of circulating
      neutrophils. After priming with phorbol myristate acetate (PMA) or tumour
      necrosis factor-alpha (TNF-alpha), an increased mean fluorescence intensity (MFI)
      was obtained on neutrophils stained with polyclonal anti-LF antibodies and with
      AGM 2.29. The kinetics of LF expression during activation demonstrated a
      progressive increase in MFI within 45 min. No increase in MFI was documented when
      primed granulocytes were stained with MoAb AGM 10.14, thus indicating that the
      epitope recognized by AGM 10.14 is not exposed at the cell surface. Following
      membrane permeabilization, performed in order to analyse the binding of anti-LF
      MoAbs to cytoplasmic LF, a marked increase in MFI was obtained by staining
      granulocytes with both anti-LF MoAbs. Indirect immunofluorescence (IIF) analysis
      confirmed that AGM 2.29 and AGM 10.14 reacted with human granulocytes, showing a
      cytoplasmic pattern on formalin-acetone-fixed neutrophils and a perinuclear one
      on ethanol-fixed cells.

PMID- 9276524
TI  - Human mast cells expressing recombinant proteinase 3 (PR3) as substrate for
      clinical testing for anti-neutrophil cytoplasmic antibodies (ANCA).
AB  - We have expressed conformationally intact, enzymatically active recombinant PR3
      in HMC-1 cells (HMC-1/PR3 cells) that is recognized by C-ANCA. Here we directly
      compared the clinical utility of C-ANCA testing by indirect immunofluorescence
      (IIF) using HMC-1/PR3 cell cytospin versus polymorphonuclear neutrophil (PMN)
      cytospin preparations and commercially available anti-PR3 ELISA kits. Two hundred
      sera were tested independently by three investigators: 101 previously determined
      to be C-ANCA-positive by routine clinical laboratory testing using standard IIF
      on PMN cytospins, and 99 control samples chosen primarily because they contained
      antibodies against other cytoplasmic target antigens. Discrepant test results
      between the two cellular substrates were found in seven samples: 2/7 were PMN
      positive and HMC-1/PR3 cell-negative (one Sjogren's syndrome, one hand injury);
      5/7 were PMN-negative and HMC-1/PR3-positive (all Wegener's granulomatosis (WG)).
      All C-ANCA-positive WG patients were also positive on HMC-1/PR3 cells. IIF using
      HMC-1/PR3 cells was as sensitive as the most sensitive anti-PR3 ELISA (79.8%
      versus 80.7%, P = 0.739), and more sensitive than standard IIF C-ANCA testing
      using PMN cytospins (79.8% versus 75.2%, P = 0.025) or the anti-PR3 ELISA with
      the least false-positive test results (79.8% versus 63%, P < 0.01). These
      findings indicate that HMC-1/PR3 cells are a very sensitive antigen-specific
      substrate for clinical anti-PR3 ANCA testing which appears superior to standard C
      ANCA testing using PMN cytospin substrates and anti-PR3 ELISA. Our results also
      suggest that in WG the C-ANCA fluorescence pattern is not caused by antibodies
      against target antigens other than PR3.

PMID- 9276525
TI  - Hyperinducible expression of the interferon-gamma (IFN-gamma) gene and its
      suppression in systemic lupus erythematosus (SLE).
AB  - Transient expression of IFN-gamma and IL-2 mRNA and its control by post
      transcriptional and suppressive mechanisms were analysed in phytohaemagglutinin
      induced peripheral blood mononuclear cells (PBMC) from 47 patients with SLE and
      31 age-matched normal donors, using quantitative hybridization with antisense RNA
      probes. In SLE, basal levels of gene expression did not deviate from those of
      normal donors, but strongly aberrant patterns were obtained upon induction. The
      ratio of subjects exhibiting highly inducible IFN-gamma gene expression in their
      PBMC to those showing moderate or low inducibility was increased five-fold in SLE
      (P = 0.003). High inducibility was observed for 43% of SLE patients and was
      equally pronounced in partial remission, mild or active disease. Inducibility of
      IL-2 mRNA, by contrast, remained similar to that for normal donors. However,
      regulation of IFN-gamma gene expression differed for mild SLE. Patients with mild
      disease showing high inducibility of IFN-gamma mRNA in their PBMC not only had
      the highest frequency of responders, but also the highest extent of an individual
      response, defined by superinduction of mRNA, to agents that relieve suppression
      (gamma-irradiation) or post-transcriptional down-regulation (cycloheximide). By
      contrast, patients with active SLE showing high IFN-gamma mRNA inducibility had
      normal suppressive capacity as well as post-transcriptional control. Hence, both
      high inducibility of the IFN-gamma gene and its suppression are relevant to
      disease. Hyperactivation of the IFN-gamma gene may be alleviated in mild SLE by a
      vigorous, concomitant activation of post-transcriptional control and of cell
      mediated suppression.

PMID- 9276526
TI  - Antibodies to beta2-glycoprotein I--a specific marker for the antiphospholipid
      syndrome.
AB  - The antiphospholipid syndrome is a disorder characterized by recurrent thrombosis
      and the presence of antibodies specific to phospholipids. However, the diagnosis
      of this syndrome is hampered by the lack of a specific laboratory test. In this
      study an ELISA for the measurement of antibodies to solid-phase beta2
      glycoprotein I (beta2-GPI) was established and compared with anticardiolipin
      antibodies for diagnosis of antiphospholipid syndrome. Significantly elevated
      levels of antibodies to beta2-GPI were found in all patients with definite
      antiphospholipid syndrome (median = 91 AU). Marginally elevated levels of
      antibodies to beta2-GPI were observed in 5% of patients with systemic lupus
      erythematosus (SLE; median = 4 AU), 1% with stroke (median = 3 AU), 13% with
      infectious mononucleosis (median = 3 AU), 10% with HIV infection (median = 3 AU)
      and 8% with VDRL false-positive serology for syphilis (median = 4 AU), but not in
      patients with rheumatoid factor, syphilis or carotid artery stenosis. In
      contrast, significantly raised levels of anticardiolipin antibodies were observed
      in 100% of patients with definite antiphospholipid syndrome, 30% with SLE, 88%
      with HIV infection, 94% with syphilis, 62% with infectious mononucleosis, 9% with
      rheumatoid factor-positive sera, 74% VDRL false-positive serology for syphilis,
      47% with stroke and 0% with carotid artery stenosis. This solid-phase assay for
      antibodies to beta2-GPI is highly specific for the antiphospholipid syndrome and
      represents an advance in the laboratory diagnosis of this disorder.

PMID- 9276527
TI  - Elevation of CD8+ CD11b+ Leu-8- T cells is associated with the humoral
      immunodeficiency in myeloma patients.
AB  - Recurrent bacterial infections due to humoral immunodeficiency are an important
      cause of death in myeloma patients. Recent data indicate that CD8+ T lymphocytes
      and a reduction of T helper type 1 cells with disease progression may be involved
      in the regulation of polyclonal immunoglobulin secretion. In mixed lymphocyte
      cultures derived from peripheral blood mononuclear cells (PBMC) of 24 myeloma
      patients with reduced immunoglobulin serum levels we investigated the association
      of CD4+ and CD8+ T cell subsets and immunoglobulin-secreting B cells (ISC) upon
      mitogenic stimulation with pokeweed mitogen (PWM) and concanavalin A (Con A). In
      supernatants of cultured PBMC of myeloma patients the spontaneous secretion of
      the type 1 cytokine interferon-gamma was reduced. After PWM stimulation reduced
      numbers of polyclonal ISC were found in 79% of patients, and monoclonal ISC were
      observed in 12% of patients. After Con A stimulation, again formation of
      polyclonal ISC was reduced, but monoclonal ISC were found in 41% of patients.
      Elevation of monoclonal and reduction of polyclonal ISC after stimulation with
      Con A were associated with an increase of CD8+ CD11b+ Leu-8- T cells (P<0.05). We
      conclude that the elevated numbers of CD8+ CD11b+ Leu-8- T cells play a role in
      the stimulation of monoclonal and suppression of polyclonal immunoglobulin
      secretion in myeloma patients.

PMID- 9276528
TI  - Localization of rat CD1 transcripts and protein in rat tissues--an analysis of
      rat CD1 expression by in situ hybridization and immunohistochemistry.
AB  - CD1 molecules are cell surface glycoproteins non-covalently associated with beta2
      microglobulin. Recently, functional features of the CD1 family such as a target
      ligand and an antigen-presenting structure for T cells have been reported. In the
      current study, tissue distribution of rat CD1 was analysed by in situ
      hybridization (ISH) in conjunction with immunohistochemistry to clarify the
      precise localization of both transcripts and proteins. CD1 transcripts were
      detected by ISH in a variety of organs: spleen, thymus, liver, lung, heart,
      kidney, small intestine and skin. In most organs, CD1 immunoreactivity paralleled
      the amount of CD1 mRNA expression and was localized in the same regions as its
      gene transcripts. However, there was a clear difference between the level of rat
      CD1 transcription and protein expression in the small intestine. CD1 mRNA was
      detected in the enterocytes of crypts of Lieberkuhn, but not in those of the
      intestinal villi, while immunoreactivity of CD1 protein was observed in the cells
      of the intestinal villi but not in those of crypts of Lieberkuhn. This suggests
      that CD1 gene transcription occurs in the enterocytes of intestinal crypts, and
      that as the cells of intestinal crypts migrate from the crypts to the intestinal
      villi, CD1 proteins are synthesized and accumulated in the intestinal villi. Such
      CD1 expression in the enterocytes appears to be consistent with migration
      associated differentiation, and suggests that rat CD1 may take part in mucosal
      immunity as a first line of defence. In addition, clear cell membrane CD1
      immunoreactivity on lymphoid cells raises the possibility that intercellular
      interaction via rat CD1 and T cell receptors may be involved in both lymphoid
      cell differentiation and immunoregulation.

PMID- 9276529
TI  - Molecular aberrations in the MHC class I-restricted pathway for antigen
      presentation in methylcholanthrene sarcomas from nude mice: discrepancies between
      MHC mRNA and surface protein.
AB  - In a previous study, we demonstrated that eight sarcomas induced by chemical
      carcinogenesis in nude mice were rejected by syngeneic immunocompetent recipients
      at a much higher rate than eight sarcomas induced with the same method in
      syngeneic immmunocompetent mice. In the present study, we investigated these 16
      sarcomas for structural and quantitative aberrations in components of the MHC
      class I-restricted antigen-processing and -presentation pathway. Considerable
      discrepancies between mRNA levels and cell surface protein expression of MHC
      class I (Kd, Dd and Ld) molecules were observed almost exclusively in the tumours
      derived from nude mice. Several of the nude mouse-derived tumours also displayed
      incongruent levels of heavy chain mRNA and beta2-microglobulin mRNA. These
      findings are taken as indications of abnormal regulation of gene transcription in
      nude mouse tumours, and if this abnormal regulation extends to the entire genome,
      it may explain the pronounced immunogenicity of these tumours. Proteasome
      composition, heat shock protein expression, TAP-molecule inducibility and
      intercellular adhesion molecule-1 expression were investigated in the same
      tumours. We found no indications of structural defects or quantitative
      differences in these molecules between the two groups of tumours.

PMID- 9276530
TI  - Therapeutic effects of preferential induction of mite-specific T helper 0 clones.
AB  - The predominance of Th2 cytokine-secreting pattern in allergic asthma has been
      known as a cause and an accelerating factor, and Th1 suppresses these allergic
      phenomena, but the role of Th0 clones is obscure. Because Th1/Th2 differentiation
      has been determined by cytokine environment, we investigated how mite-specific
      helper T cells stimulated in different cytokine environments actually influenced
      IgE and IgG4 synthesis, which are known to be regulatory immunoglobulins for
      allergic response. Th0 clones, which were mainly established in the presence of
      IL-12, provided a great deal of help for IgG4 and IgG1 synthesis, but did not
      provide help for IgE synthesis, whereas Th2 clones helped IgE synthesis
      prominently, and IgG4 and IgG1 synthesis marginally. These characteristics of Th0
      clones were also true for Th0 clones obtained from patients who were successfully
      treated with desensitization therapy. Furthermore, the differences in helper
      activity between Th0 and Th2 clones were not ascribed solely to soluble factors.
      These data indicate that IgE and IgG4 synthesis is differentially regulated by
      antigen-specific T cells, and that conversion or selection from Th2 to Th0 by the
      addition of IL-12 may exhibit therapeutic effects.

PMID- 9276531
TI  - Characterization of proliferative responses and cytokine mRNA profiles induced by
      Vespula venom in patients with severe reactions to wasp stings.
AB  - The reasons why severe allergic reactions to bee and wasp stings develop in only
      a small portion of exposed individuals are incompletely understood, but
      differences in T cell responses to venom antigens comparing allergic and non
      allergic individuals are likely to be important. To identify such differences,
      venom-induced proliferative responses and cytokine mRNA production by blood
      mononuclear cells from Vespula venom-allergic patients and non-allergic
      individuals were compared. Mononuclear cells from most venom-allergic patients
      proliferated in response to alkylated Vespula venom (7275 +/- 8387 ct/min, n =
      19), and the extent of proliferation was greater for patients with a history of
      multiple prior stings and those with high levels of venom-specific IgE. Although
      mononuclear cells from non-allergic subjects showed little or no proliferation in
      response to venom (926 +/- 711 ct/min, n = 8), production of mRNAs coding for IL
      2, IL-4, IL-5, IL-10 and interferon-gamma (IFN-gamma) in response to Vespula
      venom by cells from non-allergic subjects was detected by reverse transcriptase
      polymerase chain reaction (RT-PCR), indicating that these individuals had been
      previously sensitized to venom antigens. In contrast to the Th0 cytokine mRNA
      profile observed for non-allergic individuals, venom-allergic patients released a
      more restricted profile of cytokines following stimulation with venom. Only IFN
      gamma mRNA expression was detected in all individuals evaluated, whereas IL-2
      mRNA was not detected during the first 48 h of stimulation, and T cells from only
      one of three venom-allergic individuals produced detectable IL-4 or IL-5 mRNA.
      The difference in cytokine profiles observed comparing venom-allergic patients
      and non-allergic controls could not be attributed to intrinsic differences in T
      cells from these individuals, because polyclonal stimulation with phorbol
      myristate acetate (PMA) + ionophore induced similar cytokine mRNA profiles in the
      two groups. These studies demonstrate clear differences in the T cell responses
      of venom-allergic subjects, that may contribute to the development of severe
      allergic reactions in these individuals.

PMID- 9276533
TI  - Human peritoneal B-1 cells and the influence of continuous ambulatory peritoneal
      dialysis on peritoneal and peripheral blood mononuclear cell (PBMC) composition
      and immunoglobulin levels.
AB  - In mice, peritoneal B cells are composed of a unique B-1 cell population which
      can repopulate the intestinal lamina propria with IgA-producing cells, as well as
      contribute to the majority of serum IgM. In this study, peritoneal lymphocytes
      from patients starting continuous ambulatory peritoneal dialysis (CAPD) and from
      women undergoing bilateral tubal ligation (BTL) were analysed for the presence of
      a B-1 cell population as well as the expression of potential homing receptors. Up
      to 63% of the peritoneal B cells express surface antigen CD5, and most peritoneal
      lymphocytes express the mucosal homing receptors, alpha4 beta7 and alphaE beta7.
      When analysing serial samples collected from patients from the beginning of
      dialysis to 1 year, no marked changes were observed in serum or salivary
      immunoglobulin levels, although the peritoneal lymphocyte population was reduced
      by 50%. These data suggest that the phenotype of human peritoneal B-1 cells is
      similar to that of mice, but the contributions to the immune system may differ.

PMID- 9276532
TI  - Increased plasma levels of soluble CD23 in haemorrhagic fever with renal
      syndrome; relation to virus-specific IgE.
AB  - In 15 consecutive patients hospitalized with nephropathia epidemica, a European
      form of haemorrhagic fever with renal syndrome (HFRS) caused by Puumala virus,
      plasma concentrations of soluble CD23 (sCD23) and Puumala virus-specific IgE were
      determined. In the acute phase of illness, 11/15 patients had increased sCD23
      levels (> 91 U/ml), whereas in convalescence, values of 8/10 patients were
      normalized. Maximal sCD23 values were correlated to maximal concentrations of
      Puumala virus-specific serum IgE (r = 0.597; P = 0.025). The results are
      compatible with a known ability of sCD23 to augment IgE production.

PMID- 9276534
TI  - Analysis of extraocular muscle-infiltrating T cells in thyroid-associated
      ophthalmopathy (TAO).
AB  - TAO is characterized by an autoimmune process affecting the orbital contents. T
      cells have been suggested to have a major role in pathogenesis, but so far only
      limited data are available to clarify the extraocular muscle (EOM)-infiltrating T
      cell phenotype, antigenic reactivity and cytokine profile in TAO patients. In the
      present study, biopsies of affected EOM were taken and the infiltrating T cells
      isolated and expanded in vitro with mitogen. Their phenotype was determined by
      flow cytometric (FACS) analysis and compared with peripheral blood-derived T cell
      lines, treated in the same way from the same patient. Cytokines present in the
      supernatant after mitogen stimulation of the T cell lines were assayed by ELISA.
      In addition, cytokine mRNA present at the time of biopsy was determined by rapid
      RNA extraction from EOM and reverse transcription-amplification with specific
      cytokine oligonucleotide probes (IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL
      10, IL-12, IL-13, IL- 15, interferon-gamma (IFN-gamma), tumour necrosis factor
      alpha (TNF-alpha)). In the T cell lines from two patients, proliferation assays
      were carried out with antigens derived from thyroid gland, EOM and a thyrotropin
      (TSH) receptor preparation. Most T cell lines were CD4+, CD45RO+, and TCR
      alpha/beta+, both from the EOM and the peripheral blood. A wide variety of
      cytokines was detected by analysis of supernatants or mRNA, but the profiles were
      not identical comparing the two approaches. However, IL-4 was detected by both.
      Dose-dependent proliferation was observed in response to thyroid extract in a
      biopsy-derived T cell line. In conclusion, EOM-infiltrating T cells from patients
      with TAO, expanded in vitro, were chiefly CD4+ and produced a mixture of
      cytokines, including IL-4. The proliferation data suggest that there are thyroid
      reactive T cells in EOM.

PMID- 9276535
TI  - Oral tolerance in a murine model of relapsing experimental autoimmune
      uveoretinitis (EAU): induction of protective tolerance in primed animals.
AB  - Oral administration of uveitogenic retinal antigens suppresses the expression of
      EAU induced by a subsequent immunization with these antigens. Effectiveness and
      mechanisms of oral tolerance in EAU have mainly been studied in the acute,
      monophasic model in Lewis rats by feeding antigen prior to induction of disease.
      In this study we investigated the effect of oral tolerance induction in the acute
      as well as the chronic-relapsing models in the B10.A mouse. In acute murine EAU
      we could effectively suppress disease by induction of oral tolerance prior to
      immunization. In the chronic-relapsing EAU, antigen feeding was started only
      after the animals had recovered from their first attack of uveitis. Under these
      experimental conditions the subsequent relapse was largely prevented. These
      experiments demonstrate that oral tolerance may have practical clinical
      implications in uveitis, which is predominantly a chronic-relapsing condition in
      humans.

PMID- 9276536
TI  - Migration of human intestinal lamina propria lymphocytes, macrophages and
      eosinophils following the loss of surface epithelial cells.
AB  - Lymphocytes and macrophages are present in the normal intestinal lamina propria,
      separated from the epithelial monolayer by the basement membrane. There is
      evidence for movement of mononuclear cells through the lamina propria, entering
      from the systemic circulation and exiting via lymphatic channels. The goal of our
      studies was to investigate the capacity of cells to migrate out from the lamina
      propria into the lumen following the loss of surface epithelial cells. An in
      vitro model was therefore established in which normal human intestinal mucosal
      samples, denuded of the surface epithelium, were maintained in culture. Electron
      microscopy showed that during culture, large numbers (>2 x 10(6)/g tissue per 24
      h) of cells migrated out of the lamina propria via discrete 'tunnels' which were
      in continuity with pores (diameter <4 microm) in the basement membrane. The
      emigrating cells were T cells (68.5 +/- 5.1%), macrophages (10.5 +/- 1.3%) and
      eosinophils (7.1 +/- 1.3%). Our studies have therefore demonstrated, for the
      first time, the capacity for large numbers of lymphocytes, macrophages and
      eosinophils to migrate out of the lamina propria, via basement membrane pores. We
      postulate that such emigration of cells occurs in vivo following the loss of
      surface epithelial cells due to injury, and could represent an important form of
      host defence against luminal microorganisms and also facilitate wound repair by
      enhancing restitution by neighbouring epithelial cells, via peptide factors.

PMID- 9276537
TI  - Characterization of complement C6 deficiency in a PVG/c rat strain.
AB  - Complement C6 plays an important role in the effector phase of complement
      mediated cell lysis. Recently, a PVG/c rat strain deficient in haemolytic C6
      activity was discovered. In the present study we show that these rats lack both
      antigenic and functional C6, and that repetitive immunization of these rats with
      PVG/c+ serum results in generation of specific anti-rat C6 antibodies. The
      observed absence of rat C6 was further investigated at the genomic and
      transcriptional level using a 492-bp cDNA of rat C6, cloned from a rat liver cDNA
      library using full length human C6 as a probe. Northern blot analysis revealed
      the presence of C6 mRNA in livers of both PVG/c- and PVG/c+ rats, corresponding
      to a size of approximately 3.3 kb, although the level of C6 mRNA expression was
      approximately 100-fold less in PVG/c- rats. In addition, using rat C6-specific
      primers, positive signals were obtained in kidneys of both rat strains by reverse
      transcriptase-polymerase chain reaction (RT-PCR) analysis. Southern blot analysis
      of digested genomic DNA did not reveal evidence for large C6 gene deletions. We
      conclude that the lack of C6 protein in the PVG/c- rat strain is not due to a
      (large) C6 gene deletion, but presumably is caused by an unstable mRNA or a point
      mutation in the C6 gene resulting in an aberrant transcription of the C6 gene.
      Alternatively, a gene coding for a product involved in C6 biosynthesis that acts
      in trans may carry a mutation.

PMID- 9276538
TI  - Reduction of the DTH response is related to morphological changes of Langerhans
      cells in mice exposed to acute immobilization stress.
AB  - There is a large body of evidence indicating that stress influences immune
      competence. For example, psoriasis and atopic dermatitis may be exacerbated by
      psychic stress and related to abnormalities in the cellular constituents of the
      immune system in the skin. However, the underlying mechanisms remain unclear. We
      therefore investigated the potential of acute immobilization stress to affect the
      DTH response in BALB/c mice. DTH was significantly reduced in an immobilization
      time-dependent manner when stress exposure was just before sensitization.
      Although the number of Langerhans cells (LC) did not change under these
      conditions, marked alteration of LC morphology was observed with a significant
      decrease in area. Recovery of LC was observed within 24 h when the DTH response
      was also restored. Expression of the calcitonin gene-related peptide (CGRP),
      which inhibits LC antigen presentation, was significantly increased up to 1.6
      fold in nerve fibres of immobilized mice. We conclude that stress-induced
      suppression of DTH could be due to reduction of LC antigen presentation with
      morphological change in association with CGRP elevation.

PMID- 9276539
TI  - A global perspective on the past, present, and future of nosocomial infection
      prevention and control.

PMID- 9276541
TI  - International Federation of Infection Control: the first 10 years.

PMID- 9276540
TI  - Antimicrobial resistance: problems, laments, and hopes.

PMID- 9276542
TI  - Applying the Centers for Disease Control and Prevention and National Nosocomial
      Surveillance system methods in Brazilian hospitals.
AB  - BACKGROUND: Nosocomial infection is an important public health problem in Brazil.
      The better to understand and address this problem, we began using the National
      Nosocomial Infection Surveillance (NNIS) system in five Brazilian hospitals in
      1991. METHODS: Data were collected prospectively according to the NNIS protocol,
      by using nosocomial infection definitions from the Centers for Disease Control
      and Prevention. RESULTS: From January 1991 to June 1995, the overall nosocomial
      infection rate was 5.1% or 9.7 nosocomial infections/1000 patient-days. From the
      detailed epidemiologic information obtained by using the NNIS methods,
      interventions were designed and implemented that have reduced specific nosocomial
      infection rates. For example, the incidence of infection caused by methicillin
      resistant Staphylococcus aureus was reduced from 0.61 infections/1000 patient
      days in 1991 to 0.05 infections/1000 patient-days in 1996 (p < 0.01). The
      surgical site infection rate after cesarean section was reduced from 11.6% in
      1993 to 5.9% in 1996 (p < 0.05). Cost savings from a program to optimize the use
      of antimicrobial agents in one hospital was more than $1.8 million over a 45
      month period. CONCLUSION: The NNIS method was applicable in a wide variety of
      hospitals, even those with little or no experience with nosocomial infection
      surveillance. By using this method, we defined the detailed epidemiology of
      nosocomial infection and implemented interventions that have significantly
      reduced nosocomial infection rates while achieving substantial cost savings.

PMID- 9276543
TI  - Surveillance of colonization and infection with Staphylococcus aureus susceptible
      or resistant to methicillin in a community skilled-nursing facility.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is an important
      nosocomial pathogen in acute care hospitals and long-term care facilities. Few
      studies have been reported in private skilled nursing facilities (SNFs) not
      experiencing outbreaks of infections caused by MRSA. METHODS: From a 149-bed SNF
      with no outbreaks, we report a 1-year prospective surveillance study of S. aureus
      colonization and infection, with focus on S. aureus phenotypes, both methicillin
      susceptible (MS) and methicillin resistant (MR). Nasal and stool or rectal
      screening cultures were done on admission, and all patients underwent screening
      on at least a quarterly basis for 1 year. RESULTS: Overall, 35% of patients were
      colonized at least once with S. aureus, (72% MS, 25% MR, and 3% mixed
      phenotypes), 94% of the MRSA were ciprofloxacin resistant. Nasal colonization
      with any S. aureus was more frequent, but 13% of patients had positive results
      only in rectal specimens. Twenty-one percent of the newly admitted and 15% of
      continuing patients acquired colonization during their stay in the SNE
      Colonization was transient or persistent, persisted longer in the nares compared
      with colonization in rectal specimens, and was more stable for methicillin
      susceptible S. aureus. Nine percent of patients had development of infection with
      S. aureus. There was no indication that MRSA colonization led to more infections
      than methicillin-susceptible S. aureus. Of the 13 infected patients in whom
      cultures had previously been obtained, seven (54%) had been colonized by the same
      phenotype strains. CONCLUSIONS: In this private SNF, endemic S. aureus infections
      occur at a low frequency, reflecting a moderate level of colonization with S.
      aureus. However, a trend showing gradual increases in frequencies of colonization
      and infection is of concern and suggests that in this SNF, future intervention
      could become warranted.

PMID- 9276544
TI  - Epidemiology of needlestick and sharp injuries at a university hospital in a
      developing country: a 3-year prospective study at the Jordan University Hospital,
      1993 through 1995.
AB  - OBJECTIVE: To study the epidemiology of needlestick and sharp injuries in a
      university hospital in a developing country, Jordan. METHODS: A prospective study
      was undertaken of all needlestick and sharp injuries among workers at the Jordan
      University Hospital between 1993 and 1995. Health care workers were asked to
      report in person to the infection-control team to verify the incident and to
      respond to a questionnaire. Blood was obtained from patients and health care
      workers immediately and from the health care workers 6 months later for hepatitis
      B virus, hepatitis C virus, and HIV testing. RESULTS: During the 3-year period,
      248 health care workers had needlestick and sharp injuries. Of these, 34.6% were
      staff nurses, 19%, environmental workers, 15.7%, interns, 11.7%, residents, 8.5%,
      practical nurses, and 6% were technicians. The incidence density was highest for
      the interns followed by staff nurses and environmental workers. Of incidents,
      22.6% occurred during blood drawing, 11.3% during placing intravenous lines, 8.5%
      during administration of medication, 11% during recapping the needle, 10.5%
      during needle disposal, 12.5% during garbage collection, and 5% were caused by a
      neglected needle. Only 117 patients were identified; 36 of 62 of these had
      positive results for hepatitis B surface antigen, and 8 of 13 for hepatitis C
      virus. CONCLUSION: Needlestick and sharp injuries occur frequently in developing
      countries. Safer disposal facilities and routine hepatitis B vaccine should be
      adopted.

PMID- 9276546
TI  - Comparative sensitivity of 13 species of pathogenic bacteria to seven chemical
      germicides.
AB  - BACKGROUND: The relative resistance of diverse human bacterial pathogens to
      commonly used germicidal agents has not been established. METHODS: We measured by
      titration the survival of thirteen different bacteria after exposure to
      glutaraldehyde, formaldehyde, hydrogen peroxide, peracetic acid, cupric
      ascorbate, sodium hypochlorite, or phenol. RESULTS: Our comparative experiments
      allowed classification of the organisms' survival into four groups: (a)
      Pseudomonas aeruginosa and Staphylococcus aureus showed the most resistance, (b)
      Clostridium perfringens, Salmonella typhimurium, Staphylococcus epidermidis, and
      Escherichia coli O157:H7 showed intermediate resistance, (c) Listeria
      monocytogenes, Shigella sonnei, and Vibrio parahaemolyticus survived some
      treatments with chemical agents only in the presence of protecting protein (serum
      albumin), and (d) Vibrio cholerae, Vibrio vulnificus, Bacillus cereus, and
      Yersinia enterocolitica did not survive any of the treatments applied.
      CONCLUSION: We found species that more frequently survived exposure to germicidal
      agents were also those most commonly reported in association with hospital
      infections. Our findings suggest that resistance to disinfectants may be more
      important than pathogenicity in determining the relative prominence of an
      organism as an agent responsible for nosocomial infections.

PMID- 9276545
TI  - Incidence of percutaneous injuries at a dental school: a 4-year retrospective
      study.
AB  - BACKGROUND: Infection control training for predoctoral dental students, dental
      hygiene students, and dental assistant students has assumed an important role in
      the educational process at our institution. As part of an ongoing review of the
      curriculum at our school, we conducted a retrospective analysis of reported
      percutaneous injuries during the years 1991 through 1994 to determine whether the
      increase in infection control training introduced at the school in 1990 has had
      an effect on our rate of percutaneous injuries. METHODS: The population examined
      in this retrospective study consisted of predoctoral and postdoctoral dental
      students, dental hygiene students, dental assistant students, and staff. The data
      for this retrospective study were obtained from annual reports of occupational
      exposures incurred by students and staff. These annual reports were generated by
      compiling and summarizing all percutaneous injury incident reports that were
      prepared for that year. RESULTS: Our results indicate, that except for an
      increase in 1992, the total number and incidence of reported percutaneous
      injuries decreased from 1991 to 1994. Statistically significant decreases were
      seen in the total number of reported percutaneous injuries for all students,
      staff, and all groups combined. On the basis of data available for 1993 and 1994,
      the incidence of reported percutaneous injuries per 1000 procedures was fairly
      constant over these 2 years. Distribution of percutaneous injuries by source
      varied during the 4-year period. CONCLUSIONS: As part of the outcomes assessment
      program at our institution, we conducted a retrospective study of reported
      percutaneous injuries from 1991 to 1994. This study demonstrated that, although
      the total number of injuries decreased significantly, the rates within certain
      individual groups remained unchanged. On the basis of this observation, increased
      emphasis in the prevention of percutaneous injuries through additional training
      is indicated for these groups.

PMID- 9276547
TI  - A retrospective on infection control. Part 2: twentieth century--the flame burns.

PMID- 9276548
TI  - Adaptation and validation of a portable steam sterilizer for processing
      intrauterine device insertion instruments and supplies in low-resource settings.
AB  - BACKGROUND: Difficulties with adequately processing intrauterine device (IUD)
      insertion instruments and supplies have led to use of potentially contaminated
      items, compromising the quality and safety of IUD insertion services in
      Bangladesh. A sterilization process for IUD insertion instruments and supplies by
      using a commercially available portable steam sterilizer was developed and
      validated. METHODS: Racks provided with the sterilizer were used during
      sterilization of wrapped supplies (gloves and cotton balls). Metal compartments
      to hold insertion instruments were built to fit into the sterilizer. After
      sterilization, supplies were transported to rural service sites in plastic bags,
      whereas instruments remained in the sterilizer, which was transported in a
      carrying case. To validate the sterilizer, laboratory testing was conducted by
      using chemical and biologic indicators for steam sterilization and field testing
      in Bangladesh with chemical indicators. RESULTS: Results indicated that
      sterilization cycles were effective in achieving sterility of IUD insertion
      supplies and instruments at sterility assurance levels of 10(-5) and 10(-6),
      respectively. CONCLUSIONS: Use of this sterilizer for IUD insertion supplies and
      instruments will improve the quality of service delivery in the Bangladesh family
      planning program and has application for use in many other low-resource settings.

PMID- 9276550
TI  - Anatomy training for surgeons--a personal viewpoint.

PMID- 9276549
TI  - Influenza control in acute care hospitals.
AB  - BACKGROUND: Influenza causes increased morbidity and mortality among patients in
      longterm care facilities, but little information is available on the impact of
      influenza in acute care settings. We wished to have such information when
      revising our hospital influenza control policy. METHODS: We reviewed recent
      reports of influenza among patients in acute care hospitals and surveyed large
      (approximately 500-bed) acute care teaching hospitals by telephone to determine
      the nature of their influenza control policies. RESULTS: Seventeen reports of
      influenza outbreaks in acute care hospitals were published from 1959 to 1994.
      Influenza A caused 13 of these outbreaks. Five involved children and 12 involved
      adults. The mean number of patients in each outbreak was 14 (range 1 to 49), with
      a mortality rate of 0% to 50% (median 0%, mean 6.5%). Health care workers were
      implicated in transmission in five reports. Vaccine was used infrequently during
      the outbreaks, and use of chemoprophylaxis was not reported. Our survey of
      current practices in 15 university-affiliated hospitals from 12 states revealed
      that all offered vaccine in the fall but none required either immunoprophylaxis
      or chemoprophylaxis at any time. Only three had formal policies detailing
      management of influenza in the hospital. CONCLUSIONS: Nosocomial influenza in
      acute care hospitals is infrequently reported and associated with a low mortality
      rate. Health care workers rarely comply with preventive measures, and few
      institutions have formal influenza control policies.

PMID- 9276551
TI  - Targeting medical students to promote women in surgery.
AB  - The under-representation of women in surgical subspecialities is a well-aired
      topic. Most efforts to redress the surgical gender balance have, to date, been
      directed at opportunities for women in surgical training. We report on a one-day
      symposium organized by the Royal College of Surgeons of Edinburgh to promote
      interest in taking up a surgical career, aimed at senior women medical students
      and newly qualified doctors. Although 130 of the attendees who were surveyed did
      not change their opinion about the four most off-putting aspects of a surgical
      career, the symposium succeeded in increasing the appeal of a surgical career in
      50%, apparently by the intensive exposure to a large and varied sample of female
      surgical role models.

PMID- 9276552
TI  - Current position of advanced laparoscopic surgery of the liver.
AB  - With the improvement of laparoscopic techniques and the development of new and
      dedicated technologies, endoscopic liver surgery has become feasible. While wedge
      liver resections are performed more and more frequently, laparoscopic anatomical
      liver resections are still at an early stage of development and are somewhat
      controversial. In 1993 we initiated formal laparoscopic liver resections in
      selected patients. From 1993 to December 1995 20 patients underwent endoscopic
      formal resections: the procedures comprised six left hepatectomies, five right
      hepatectomies, one of which extended to the segment IV, three mesohepatectomy,
      five segmentectomies and one bisegmentectomy. The operation time ranged from 120
      to 270 min (average 193 min). In 17 out of 20 cases a Pringle manoeuvre was
      performed (mean occlusion time 45 min). No intra-operative complications occurred
      and there were no conversions in the whole series. Average intra-operative blood
      loss was 397.5 mL and 35% of patients required intro-operative blood
      transfusions. Post-operative mortality rate was 5% and post-operative morbidity
      rate was 45% (one coagulopathy with severe trombocytopaenia, six pleural
      effusions, one bile collection and four hematomas of the trocar sites). Such
      preliminary data are comparable with those of a group of 65 patients who
      underwent open anatomical liver resections from 1992 and 1995. Far from being a
      routine technique in liver surgery, the laparoscopic approach to forma liver
      resections may be a promising procedure in selected patients.

PMID- 9276553
TI  - Laparoscopic inguinal hernioplasty: a community hospital's experience.
AB  - Although controversial, laparoscopic inguinal hernia repair has become
      increasingly popular among surgeons. The overall advantages of this procedure
      over conventional hernia repair have not as yet been substantiated. One hundred
      and three consecutive laparoscopic, transabdominal, preperitoneal inguinal hernia
      repairs in 91 patients were evaluated retrospectively. Patients' satisfaction was
      assessed using the Visick grading system. The mean follow-up was 18.3 months. One
      case was converted to an open procedure. Eighty-eight patients (91%) were
      discharged on the day of surgery. Eighty-seven patients (96%) were satisfied with
      the operation (Visick grades I & II). Twenty-nine patients who previously
      underwent a traditional open herniorraphy stated that they would have preferred
      the laparoscopic method if they had the choice. Early complications included
      wound infection (n = 1), urinary retention (n = 1) and intestinal obstruction
      necessitating a laparotomy (n = 1). All patients were ambulating without
      significant pain after a mean of 7.6 days, and returned to work after 2.4 weeks
      on average. There was one case of recurrence. In conclusion, patients are
      satisfied with the laparoscopic hernioplasty technique, which is associated with
      a low morbidity and short term recurrence rate. Laparoscopic hernioplasty should
      be considered a viable and valuable alternative to the open method. It appears
      especially attractive for recurrent or bilateral hernias.

PMID- 9276554
TI  - Risk of contamination from laparoscopic carbon dioxide insufflators.
AB  - Ten high flow laparoscopic carbon dioxides insufflators were examined to
      determine whether there was significant particulate or bacterial contamination of
      the gas delivered to patients. The gas delivery tubing and connections in the
      insufflators were also examined for the presence of bacterial colonization and
      for evidence of retrograde passage of body fluids to the insufflator. Metallic
      particulate debris was recovered from gas from all 10 insufflators. Staphylococci
      were recovered from the insufflated gas from one insufflator and from the
      internal tubing of three insufflators. Swabs from the internal tubing of two
      insufflators showed evidence of contamination by blood. The metallic particulate
      contamination of the insufflated gas may not be of clinical significance but the
      presence of bacteria and blood is a concern. Simple measures to minimize the risk
      of retrograde flow of gas and fluid to the insufflator should be followed and the
      provision of a filter between the patient and the insufflator is recommended.

PMID- 9276555
TI  - A proposed anatomical classification of the pulmonary fissures.
AB  - No method of classifying pulmonary fissures currently exists, however, the nature
      of the fissure is of great importance in planning operative strategy for
      thoracoscopic pulmonary resection where an incomplete fissure may contribute to
      post-operative air leakage. In order to provide a framework for description of
      operative technique and to allow meaningful comparison between different surgical
      series, we propose a fissural classification based on both the degree of
      completeness of the fissures and the location of the pulmonary artery at the base
      of the oblique fissure. Completeness of a fissure is graded in four stages: grade
      1--complete fissure with entirely separate lobes; grade 2--complete visceral
      cleft but parenchymal fusion at the base of the fissure; grade 3--visceral cleft
      evident for part of the fissure; grade 4--complete fusion of the lobes with no
      evident fissural line. The relationship of the pulmonary artery to the oblique
      fissure is described by the term 'fissural balance'. The pulmonary artery lies
      centrally to the oblique fissure in a 'normally balanced' fissure. Anterior or
      posterior displacement of the artery is referred to as anterior or posterior
      'imbalance'.

PMID- 9276556
TI  - Foreign bodies in the tracheobronchial tree in Sudanese patients.
AB  - A prospective study of patients with foreign bodies in the tracheobronchial tree
      attending Khartoum North Teaching Hospital was carried out. The duration of the
      study was 3 years. The number of patients studied was 46. The majority were
      toddlers aged between 18 months and 2 years. There was no sex predominance. The
      most frequently encountered foreign bodies in the bronchi were ful sudani
      (peanut, Arachis hypogea), and tasaly seeds (water melon, Citrillus vulgaris).
      The foreign bodies were found more commonly in the right bronchus in 87% cases.
      Negative roentogenogram did not exclude presence of foreign bodies in the
      bronchi. Persistence of symptoms and signs were taken as the indication for the
      bronchoscopy. The mortality rate in this series was 4.3%.

PMID- 9276558
TI  - Double breasting technique for residual cavity in hepatic hydatid.
AB  - Nine patients with univescicular echinococcal cysts in the liver were subjected
      to operative removal followed by a novel technique of obliteration of the
      residual space in the liver. The simple double breasting procedure was not
      associated with any complications and there was a considerable reduction in the
      median operating time (2 h 15 min) as well in median hospital stay (5 days).
      There was no recurrence with a median follow-up of 2 years and 4 months. None of
      the patients received albendazole either prophylactically or post-operatively.

PMID- 9276557
TI  - Palliative surgery in malignant obstructive jaundice: prognostic indicators of
      early mortality.
AB  - A prospective analysis of 50 patients undergoing palliative bypass surgery for
      incurable malignant obstructive jaundice was carried out in an attempt to
      identify factors predicting post-operative mortality. Five clinical and nine
      laboratory parameters were studied. Fourteen patients died within 30 days of
      surgery. It was seen that levels of haemoglobin, hematocrit and serum albumin
      levels were significantly lower while serum bilirubin was significantly higher in
      patients who died compared with the survivors. Patients having Hb < 10 Gm/dL,
      serum bilirubin > 350 micromol/dL, serum albumin < 2.5 g/dL and prothrombin index
      < 60% exhibited a higher percentage of mortality. On multivariate analysis,
      levels of haemoglobin, serum albumin and serum bilirubin could be used to
      independently predict the outcome with an accuracy of 86%. This was validated by
      prospectively applying the regression equation derived from the first 30 patients
      to the next 20 patients. It was seen that the predicted outcome correlated with
      the actual outcome with a correlation coefficient of 0.5098 (P = 0.01). It is
      concluded that in patients with high bilirubin, low haemoglobin and low albumin
      levels palliative surgical procedures carry a high risk of post-operative
      mortality and non-surgical methods may be more suitable.

PMID- 9276559
TI  - Management of foreign bodies of the rectum: report of 21 cases.
AB  - This is a report of 21 patients treated for non-therapeutic introduction of
      rectal foreign bodies in our institution. Nine out of 18 patients had manual
      transanal extractions performed under general anaesthesia while eight patients
      required insertion of retractors and gynaecological forceps. In three patients
      the vacuum from the hollow objects was abolished by passing a catheter through
      the anus to a point above the object. One of the patients required colotomy for
      retrieval of a wooden object. In three patients free perforations were obvious
      clinically with peritoneal signs and free air on plain abdominal radiographs.
      Treatment was end-sigmoid colostomy and mucous fistula, oversewing of the
      perforation and peritoneal irrigation. There were no deaths and only one
      complication occurred, a rectovaginal fistula.

PMID- 9276560
TI  - Amputation and prostheses in Khartoum.
AB  - One hundred and seventy patients with major lower limb amputation (MLLA)
      presenting to The National Prosthetic-Orthotic Centre (NPOC) in Khartoum over a 1
      year period were studied. There were 141 males and 29 females giving a M:F ratio
      of 4.9: 1.0, with mean age of 37 years (range 5-72 years). Forty-one patients
      (24%) underwent amputation of diabetic septic foot, 30 patients (17.6%) underwent
      amputation as a result of trauma from road traffic accidents and Madura foot, and
      war injuries accounted for 29 amputations (17%). One hundred and eleven patients
      had below knee amputation (BKA), 52 had above knee amputation (AKA) and seven
      patients had Syme's amputation. Diabetic amputees had higher rate of revisional
      surgery compared with others because of sepsis and/or flap necrosis. Stump pain
      was reported by amputees with excessive scarring of the stump and those with
      undue prominence of bony ends. There are two types of prostheses provided by the
      NPOC for both BKA and AKA: the peg leg and the conventional prostheses. The
      Syme's amputees were fitted with either simple hoof or articulated prostheses
      with solid ankle cushion heel (SACH). The peg leg consists of a leather lined
      side bearing metal socket connected to a rocker base by side steels. It is used
      by the country natives as it suits different weather and job conditions,
      particularly farming, and it can be repaired locally. The urban population use
      the conventional prostheses which is lighter in weight, can be put on and taken
      off easily and is cosmetically acceptable. However, these prostheses are more
      expensive and require frequent repair or replacement. The functional outcome of
      patient's rehabilitation with the prostheses was significantly affected by the
      level and indication of amputation. Those with BKA and those amputated because of
      trauma or Madura foot experienced better functional outcome compared with the
      diabetics, independent of age. 50% of patients with the AKA and 19% of those with
      BKA reported poor functional outcome. Surgeons should be more involved with the
      long-term evaluation of functional outcome in such patients, to offer help if
      feasible and to modify their technique for future procedures.

PMID- 9276561
TI  - Deliberate self-harm as a cause of persistent discharge from arthroscopic
      portals.
AB  - Persistent discharge and bleeding from arthroscopy portals are rare
      complications. We report three cases which occurred as a result of deliberate
      self-harm. To our knowledge the occurrence of self-inflicted injury following
      arthroscopy has not been reported. Although suspicion of such activity may be
      delayed we consider it important to be aware of the possibility of this behaviour
      and to seek specialist help early in order to reduce the likelihood of further
      permanent physical damage.

PMID- 9276562
TI  - Ultrasound compared with radiographic assessment in developmental dysplasia of
      the hip.
AB  - Two hundred and seventy-two patients 'at risk' for hip dislocation underwent
      ultrasound examination. From this group 60 patients had ultrasound evidence of
      DDH (developmental dysplasia of the hip). Thirty-eight of these were also
      assessed radiographically. The diagnosis of dislocation was more accurate with
      sonography, where there was only one scan showing an equivocal dislocation (not
      dislocated on arthrography). On radiographic evaluation there were six cases of
      equivocal dislocation, and one case which was wrongly diagnosed as dislocation
      (dysplastic on sonography and arthrogram). A high level of agreement was found
      between the two methods in the diagnosis of dysplastic and normal hips (88 and
      86% respectively). In view of the advantages of sonographic evaluation of the
      dislocated and dysplastic hip: safe (no ionizing radiation), dynamic and static
      assessment, accurate (prior to femoral epiphysis ossification) and non-invasive
      (compared with arthrogram), radiographic and arthrographic assessment of the hip
      has been largely abandoned in our practice.

PMID- 9276563
TI  - Can operating time be used as a method of planning a plastic surgeon's operating
      list and assessing performance?
AB  - Analysis of a consultant plastic surgeons elective theatre list over a 1-year
      period with a view to estimating case number, case work load and operating times
      indicated that the latter cannot be reliably used as a performance indicator.
      While operating time can be of interest in planning the composition of a theatre
      session, more useful information can be obtained by assessing work load in
      conjunction with the case numbers. Various problems in using the BUPA
      intermediate equivalent values for workload are outlined.

PMID- 9276564
TI  - An analysis of the factors contributing to mortality rates in burns patients
      treated at Mpilo Central Hospital, Zimbabwe.
AB  - We present a retrospective analysis of 49 patients (61% males and 39% females)
      with burns who died at Mpilo Central Hospital between January 1990 and December
      1993. Of the patients, 61% (30/49) were in the paediatric age group, with 55%
      (27/49) under 2 years of age. Most burns occurred at home (79%) and 17% of the
      burns occurred at the workplace. The commonest burning agents were hot water
      (39.5%) and open fires (39.5%). The surface area of burns ranged from 10 to 88%
      with a mean of 35%. Deep partial thickness and full thickness burns accounted for
      52% of cases. All the patients required active resuscitation with intravenous
      fluids. A total of 35 organisms were isolated on 18 pus swabs. The most commonly
      isolated organisms were Staphylococcus aureus (43%) and Pseudomonas (23%). The
      main factors contributing to death were septicaemia (n = 15), pneumonia (n = 10)
      and acute renal failure (n = 7). The majority of patients (65%) died within 10
      days, 61% of whom were children. The average time to death was 14 days (range 1
      64 days). It is clear that some patients with severe burns will die regardless of
      how well they are managed. The key to successful management of those patients who
      should survive lies in early presentation and active resuscitation, prevention
      and control of infective complications and adequate nutritional support.

PMID- 9276565
TI  - Swimming for laryngectomy patients.
AB  - We describe how to start up and run a swimming club for laryngectomy patients. We
      detail the precautions required, and present the benefits to patients. This paper
      is based on the experience acquired through contact with the Sunderland
      Laryngectomy Swimming Club.

PMID- 9276566
TI  - The management of pyloric stenosis in a district hospital.
AB  - Over a 10-year period, 80 infants were admitted with a diagnosis of pyloric
      stenosis. Seventy-nine underwent surgical pyloromyotomy (63 male, 16 female; mean
      age 5.6 weeks). Fifty-nine infants (75%) were operated upon by one of four
      consultant surgeons and 20 (25%) operations were undertaken by a registrar.
      Seventy operations (89%) were performed during normal working hours and thirty of
      these (43%) were placed first on the operating list. The mean length of stay was
      6.9 days. Three infants required re-operation: there were two instances of wound
      dehiscence and one episode of bleeding from the edge of the pyloromyotomy. There
      were no deaths. The morbidity and mortality in this series was comparable with
      published results from specialist units.

PMID- 9276567
TI  - Anal dilatation in the management of painful defaecation in children.
AB  - Painful defaecation is a common and distressing problem in children. A
      retrospective study has been made of 27 such children who underwent examination
      under anaesthetic and anal dilatation as part of their overall management. At
      operation, fifteen were found to have perianal skin inflammation and fissuring.
      Follow-up was continued where possible until symptoms resolved. The length of
      follow-up ranged from 1 to 18 months (mean 7 months). At discharge, 21 of the
      children were cured or substantially better. The author concludes that anal
      dilatation may help in the management of these children but only as part of an
      overall strategy of medical care.

PMID- 9276568
TI  - Streptococcal necrotizing fasciitis complicating elective inguinal herniorrhaphy.

PMID- 9276570
TI  - Genital herpes masquerading as anal fissures.
AB  - Sexually transmitted genital infections in women may affect the vulva, vagina,
      cervix and urethra, or more rarely the rectum. Proctitis, a common finding in
      surgical clinics, can be caused by sexually transmitted infections including
      gonococcal and chlamydial. This possibility should be considered by
      coloproctologists and general surgeons when sexually active young women present
      to them with relevant anorectal symptoms, particularly if the symptoms are of a
      relapsing nature. Unless specifically questioned, the patient may fail to see the
      relevance of a history of an anogenital infection. The case reported provides an
      example.

PMID- 9276569
TI  - Typhoid perforation of small bowel: a study of 72 cases.
AB  - Typhoid perforation, a serious complication of typhoid fever, is still common in
      Third World countries and has a mortality rate between 1 and 39.3% according to
      various reports. There are different approaches to the treatment of typhoid
      perforation. Early surgical intervention with simple closure of the perforation
      in two layers has good results and negligible mortality. It is easy to perform
      and can be carried out, even by a trainee surgeon.

PMID- 9276572
TI  - Mammary hamartoma: is clinical diagnosis possible?
AB  - Mammary hamartoma is a rare benign lesion of the female breast. Diagnosis is
      usually made by either radiological and or histological means. Clinical diagnosis
      has been reported to be difficult. Between December 1994 and June 1995, three
      patients were found to have mammary hamartomas. All of them presented with breast
      lump greater than 6 cm in size. All hamartomas were well-delineated, soft and
      lobulated. Mammogram in these patients showed typical radiological 'breast in the
      breast' appearance of mammary hamartoma. A correct clinical diagnosis of mammary
      hamartoma was made in the third patient after the experience of management gained
      through the first two patients with mammary hamartoma. We believe that clinical
      diagnosis of mammary hamartoma is possible with both awareness of and experience
      of examining patients with this rare disease.

PMID- 9276571
TI  - 'Gossypiboma': an unusual cause of perinephric abscess.
AB  - Retained surgical sponges, euphemistically called 'Gossypibomas', are rare
      occurrences which are infrequently reported in the literature because of legal
      implications. Their manifestations and complications are so variable that
      diagnosis is difficult and patient morbidity is significant. In this note, we
      discuss the classical ultrasound, computerized tomography (CT) scanning and
      magnetic resonance imaging (MRI) features, which, in the presence of a high index
      of suspicion in a patient who has previously been operated upon, will greatly aid
      in the pre-operative diagnosis of this unfortunate complication. The gossypiboma
      masquerading as a perinephric abscess has not been previously reported.

PMID- 9276573
TI  - Carcinoma of the gall-bladder producing mucous obstruction of the common bile
      duct: a cautionary note.
AB  - A patient with an early gall-bladder carcinoma with jaundice due to mucous
      obstructing the common bile duct is presented. This has not previously been
      reported in the literature and has management implications. Proceeding
      immediately to endoscopic stenting in these patients may result in the
      opportunity for potentially curative surgery being missed.

PMID- 9276574
TI  - The illness of Franz Schubert: a case of misdiagnosis.

PMID- 9276575
TI  - Distal mucus fistula following resection for perforated sigmoid diverticular
      disease.

PMID- 9276576
TI  - The influence of total knee replacement on lower limb blood flow.

PMID- 9276577
TI  - Assessment of outcome after thoracoscopic sympathectomy for hyperhidrosis in a
      specialized unit.

PMID- 9276578
TI  - The use of botulinum toxin for anal fissure.

PMID- 9276579
TI  - The management of chronic fissure in ano with botulinum toxin.

PMID- 9276580
TI  - The management of chronic fissure in ano with botulinum toxin.

PMID- 9276581
TI  - Evidence-based medicine: why all the fuss? This is why.

PMID- 9276582
TI  - Restoring the balance: evidence-based medicine put in its place.

PMID- 9276583
TI  - The unacceptable face of evidence-based medicine.

PMID- 9276584
TI  - From EBM to CSM: the evolution of context-sensitive medicine.

PMID- 9276585
TI  - A Popperian perspective of the term 'evidence-based medicine'.
AB  - If the term 'evidence-based medicine' conveys more than is conveyed by the word
      medicine, then there must be a way to distinguish between evidence-based medicine
      and non-evidence-based medicine. In particular, there must be a logically
      acceptable way to classify medical decisions as justified or unjustified by
      scientific evidence. In this essay I examine the nature of medical theories, the
      nature of the evidence that is produced by empirical tests of medical theories,
      and the relation of medical decisions to both. I conclude that attempts to
      classify medical decisions as justified or unjustified by scientific evidence
      have no foundation in logic and that the term 'evidence-based medicine' is
      logically indistinguishable from the term 'medicine'. The use of the term
      'evidence-based medicine' calls for a new type of authoritarianism in medical
      practice.

PMID- 9276586
TI  - On evidence, embellishment and efficacy.
AB  - Evidence-based medicine (EBM) - to use a vogue word - is the contemporary mantra
      of many academic physicians. Unfortunately, the evidence they consider, although
      superficially convincing, is often slanted, occasionally deliberately, but more
      often as a result of carelessness and defects in study design. These biases and
      confounding factors are often hidden and arcane and seriously impair objective
      assessment. Such defects can only be detected when all investigators agree to go
      along with Bradford Hill's dictum, namely 'It is the essence of science to
      disclose both the data upon which a conclusion is based and the methods by which
      the conclusion is obtained'; a cardinal rule more often honoured in the breach
      than the observance.

PMID- 9276587
TI  - Evidence-based medicine, practice variations and clinical freedom.
AB  - Much of cardiovascular disease can be treated on the basis of the results of
      large clinical trials and can be considered 'evidence-based'. However, trial
      results are not infallible and it is important to recognize their limitations.
      Despite the evidence, widespread variation exists in medical practice between and
      within countries; the reasons may be cultural, or may indicate poor medical
      education. Purchasing authorities have to do the best they can with available
      evidence, and our full evidence base needs to include costs; in some instances we
      now have evidence of benefit from treatment that we almost certainly cannot
      afford. Evidence-based medicine is a further - but possibly an acceptable -
      limitation to clinical freedom.

PMID- 9276588
TI  - Scientific knowledge in medicine: a new clinical epistemology?
AB  - Technological developments in the field of communications have widened access to
      research evidence and, as a result, scientific epistemology is in the ascendancy
      in the area of medical knowledge. This has been the subject of vigorous debate
      within the medical profession itself, with many opposing the increasing weight
      given to research evidence at the expense of expert opinion. Medicine has a
      professional culture which identifies knowledge with particular individuals - a
      'person culture'. Much of the authority of physicians derives from the
      presumption that medical professionals have privileged access to medical
      knowledge. Scientific epistemology, on the other hand, identifies knowledge with
      a process of investigation. The esoteric knowledge to which expert individuals
      claim privileged access has no currency in this process. Because of this, the
      rise of scientific epistemology in medicine partially undermines the profession's
      authority. Access to scientific research evidence can be used to undermine the
      individual authority of professional experts. Illustrative examples are given of
      the nature of debate within a 'person culture' and of ways in which research
      evidence has been used to challenge the authority of physicians.

PMID- 9276589
TI  - Evidence-based medicine and public health.
AB  - Much of the everyday work of public health professionals is concerned with the
      implementation of evidence-based medicine (EBM). Is this likely to improve the
      quality of the health service that patients' receive? In this paper, I argue that
      EBM is unlikely, by itself, to improve the dimensions of quality as defined by
      Maxwell (1994). This is because EBM relies on the individual doctor doing the
      right thing all of the time. Open systems theory is a way of looking at the
      influences of the environment on individual clinical behaviour. Using this
      perspective, it is easy to see why EBM will fail to improve patient care
      dramatically. The environment in which we work is a much bigger influence on us
      than we care to admit. I use some published examples to look at the way that the
      environment affects clinical behaviour to the detriment of the overall service
      quality. As public health professionals, we should be more concerned with the
      outcome of the service than with the specifics of a particular consultation. In
      this context, EBM is likely not to be a very useful tool for public health
      professionals.

PMID- 9276590
TI  - Logical limits of randomized controlled trials.

PMID- 9276591
TI  - Evidence-based medicine.

PMID- 9276592
TI  - Evidence-based diagnosis.
AB  - Diagnosis, the most important aspect of clinical medicine, remains as much an art
      as a science. It depends more on skilled history taking than on examination or
      studying the results of tests. Evidence-based medicine only follows when a
      correct diagnosis has been made. The diagnosis depends on knowing what happens
      rather than the more exciting academic teaching about why things happen. The
      factual knowledge and logic needed to make a diagnosis are discussed.

PMID- 9276594
TI  - 90th anniversary of the Mayo medical records system.

PMID- 9276593
TI  - Towards a competency grid for evidence-based practice.

PMID- 9276595
TI  - Sputum screening by quantitative microscopy: a reexamination of a portion of the
      National Cancer Institute Cooperative Early Lung Cancer Study.
AB  - OBJECTIVE: To investigate the hypothesis that image cytometry of sputum specimens
      can detect squamous carcinoma without requiring visually abnormal cells. DESIGN:
      The sensitivity and specificity of image cytometry were evaluated in a case
      control study. MATERIAL AND METHODS: Seventy-three sputum slides from the Mayo
      portion of the National Cancer Institute Cooperative Early Lung Cancer Study were
      restained by a modified Feulgen method. We examined 40 slides from 9 patients in
      whom squamous carcinoma developed and 33 slides from 11 patients in whom no
      cancer developed during a follow-up of at least 5 years. Images of normal
      epithelial nuclei were collected by using an automated image cytometer.
      Discriminant analysis was used to determine differences in DNA distribution of
      normal nuclei in sputum specimens from noncancer patients versus normal nuclei in
      sputum samples from patients in whom carcinoma developed. RESULTS: By using
      features based on DNA distribution, 74% correct classification of nuclei was
      possible without human review of the material and without the use of visually
      abnormal nuclei. A receiver operating characteristic curve demonstrated
      sensitivities and specificities, including 40% sensitivity and 90% specificity.
      CONCLUSION: Although this study was limited to 20-year-old slides and squamous
      cell carcinoma, automated image cytometry detected a substantial proportion of
      patients with squamous cell cancer without using visually abnormal nuclei.

PMID- 9276596
TI  - Detection of newborn aneuploidy by interphase fluorescence in situ hybridization.
AB  - OBJECTIVE: To test fluorescence in situ hybridization (FISH) probes for rapid
      detection of aneuploidy of chromosomes 13, 18, 21, X, and Y from newborn
      uncultured blood samples. MATERIAL AND METHODS: Directly labeled, multicolored,
      commercially available FISH probes for the five aforementioned chromosomes were
      validated, and their hybridization efficiencies were established. In a blinded
      study, eight trisomic samples were tested by this FISH method. RESULTS: The
      hybridization efficiency based on metaphase evaluation of each of the five probes
      was 100%, and no cross-hybridization occurred. The mean interphase hybridization
      efficiencies of the probes for chromosomes 13, 18, 21, X, and Y were 97.4 %, 89.4
      %, 96.1%, 94.4 %, and 100 %, respectively. The eight abnormal samples were
      identified as trisomy 21 (in six), trisomy 13 (in one), and trisomy 18 (in one).
      CONCLUSION: The screening of aneuploidy of newborns for chromosomes 13, 18, 21,
      X, or Y by interphase FISH is rapid, reliable, and cost-effective. The test is
      especially suitable for medically urgent cases as a screen, followed by a
      standard chromosome analysis.

PMID- 9276597
TI  - Worsening left ventricular performance on serial exercise radionuclide
      angiography does not identify high-risk patients.
AB  - OBJECTIVE: To determine whether worsening exercise performance on serial exercise
      radionuclide angiography identifies patients at increased risk of future cardiac
      events. MATERIAL AND METHODS: One hundred nine medically treated patients with
      previous Q-wave myocardial infarction underwent two exercise radionuclide
      angiographic studies at least 6 months apart (median, 16 months) without an
      intervening clinical event. Worsening exercise performance between the two
      studies was defined by five criteria: (1) lower (5% or more) peak exercise
      ejection fraction; (2) worsening peak exercise wall motion score; (3) combination
      of criteria 1 and 2; (4) worsening serial delta (exercise - rest) ejection
      fraction; or (5) increasing exercise ST-segment depression of 1 mm or more.
      Patients were followed up for a median duration of 3.9 years after the second
      exercise study. RESULTS: Five cardiac deaths and 10 nonfatal myocardial
      infarctions occurred during follow-up. A Cox proportional hazards analysis failed
      to show an association between any of the aforementioned variables and cardiac
      events. Of the 15 patients with cardiac events, 4 (27%) had a lower (5% or more)
      exercise ejection fraction and 2 (13%) had a worsening exercise wall motion
      score. Of the 94 patients without cardiac events, 37 (39%) had a lower (5% or
      more) exercise ejection fraction and 28 (30%) had a worsening serial exercise
      wall motion score (not a statistically significant difference). CONCLUSION:
      Worsening exercise performance on serial exercise radionuclide angiography does
      not identify patients at increased risk of future cardiac events.

PMID- 9276598
TI  - Hereditary disorders of purine and pyrimidine metabolism: identification of their
      biochemical phenotypes in the clinical laboratory.
AB  - OBJECTIVE: To describe a laboratory approach to the diagnosis of hereditary
      diseases of purine and pyrimidine metabolism and emphasize clinical situations in
      which these disorders should be considered in the differential diagnosis. DESIGN:
      Disease-specific patterns were identified in random specimens of ultrafiltered
      urine by using gradient high-performance liquid chromatography with diode-array
      detection, and reference ranges were established for uric acid, hypoxanthine,
      xanthine, and uracil expressed per creatinine in random specimens of urine.
      MATERIAL AND METHODS: Diagnostically significant purines and pyrimidines were
      separated with use of a Supelco LC-18-S nucleoside column eluted with 25 mmol/L
      ammonium acetate buffer and acetonitrile-methanol-water. Biologic fluids were
      prepared by ultrafiltration after addition of 3-methyluridine as internal
      standard. We used specimens negative for screening of metabolic disorders to
      establish reference ranges. RESULTS: Disease-specific patterns were identified in
      specimens with purine and pyrimidine disorders and several urea cycle disorders
      characterized by increased production of pyrimidine. CONCLUSION: The approach
      described identified disease-specific patterns of purine and pyrimidine disorders
      and several urea cycle disorders. We suggest that testing for purine and
      pyrimidine disorders be done in specimens evaluated in metabolic laboratories for
      "screening for inborn errors of metabolism."

PMID- 9276599
TI  - Alice Hamilton--pioneer in industrial medicine.

PMID- 9276600
TI  - Management of colonoscopic perforations.
AB  - OBJECTIVE: To document our evolving surgical management of colonoscopic
      perforation and examine factors crucial to the improvement of patient care.
      DESIGN: We conducted a computer-based retrospective analysis of medical records
      (1980 through 1995). MATERIAL AND METHODS: Among 57,028 colonoscopic procedures
      performed, 43 patients (0.075%, or 1 perforation in 1,333 procedures) had a
      colonic perforation. Two additional patients were treated after colonoscopy
      performed elsewhere. The outcomes analyzed included surgical morbidity and
      mortality. RESULTS: Twenty-six women and 19 men who ranged in age from 28 to 85
      years (median, 69) were treated for colonic perforation. More than 80% of
      perforations occurred during the latter half of the study period because of the
      increased volume of colonoscopic procedures (8 perforations among 12,581
      examinations from 1980 through 1987 versus 35 perforations among 44,447
      colonoscopies from 1988 through 1995). Emergency laparotomy was performed in 42
      patients (93%). Perforations occurred throughout the colon: right side = 10;
      transverse = 9; and left side = 23. Three patients without evidence of peritoneal
      irritation fared well with nonoperative management. Most patients underwent
      primary repair or limited resection in conjunction with end-to-end anastomosis.
      In 14 patients (33%), an ostomy was created. One patient underwent laparotomy
      without further treatment. Intra-abdominal contamination ranged from none (31%)
      to local soiling (48%) to diffusely feculent (21%). Postoperative complications
      occurred in 12 patients and were associated with older age (P = 0.01), large
      perforations (P = 0.03), and prior hospitalization (P = 0.04). No postoperative
      deaths occurred. CONCLUSION: Despite a consistently low risk of colonic
      perforation, the increasing use of colonoscopy in our practice has resulted in an
      increased number of iatrogenic colonic perforations. In order to minimize
      morbidity and mortality, prompt operative intervention is the best strategy in
      most patients. Non-operative management is warranted in carefully selected
      patients without peritoneal irritation.

PMID- 9276601
TI  - Malignant pyodermas revisited.
AB  - The concept of malignant pyoderma (MP) has created controversy since its origin.
      The distinction of this disease from pyoderma gangrenosum was based on clinical
      criteria and response to treatment. Herein we discuss our current ideas on this
      entity and its possible relationship to Wegener's granulomatosis (WG). Follow-up
      data from the three original cases of MP are reported, as well as additional
      clinical and laboratory data from cases subsequently thought to represent MP.
      Many of these cases have similar clinical features such as facial and
      periauricular ulceration and occasionally signs or symptoms of WG, including
      positive titers of antineutrophil cytoplasmic antibodies (with a diffuse
      cytoplasmic staining pattern) (cANCA). MP represents a distinctive clinical
      disorder and may be a dermal manifestation of WG. Some cases of MP may represent
      pyoderma gangrenosum or other undefined systemic illnesses. Such cases of WG can
      be distinguished on the basis of clinical, histopathologic, and laboratory
      evidence including cANCA titers. MP should no longer be used as a final clinical
      diagnosis.

PMID- 9276603
TI  - Practical considerations for managing asthma in adults.
AB  - Asthma is a common, chronic inflammatory disorder of the airways associated with
      pronounced health and economic consequences. Consistent and effective education
      that promotes an active partnership with patients remains the cornerstone for
      managing asthma. Identification and control of asthma triggers, regular
      monitoring of lung function, and adequate pharmacologic therapy are three other
      critical components. In this article, we describe several practical
      considerations for developing a collaborative, multidisciplinary approach to
      asthma care that emphasizes patient education and strengthens the partnership
      between patients and health-care professionals.

PMID- 9276602
TI  - Treatment of antineutrophil cytoplasm autoantibody-associated systemic
      vasculitis: initiatives of the European Community Systemic Vasculitis Clinical
      Trials Study Group.
AB  - The diagnosis, treatment, and monitoring of the primary systemic vasculitides
      associated with circulating antineutrophil cytoplasm autoantibodies (ANCA) have
      formed the focus of a multicenter collaborative study. Consensus has been reached
      on criteria for classification, clinical subgroupings by extent and severity of
      disease, and "standard" and "best alternative" therapeutic regimens. Two series
      of randomized controlled trials have been designed; their aims are (1) to
      harmonize current approaches to treatment and (2) to test the value of newer
      therapeutic agents. In support of these trials, semiobjective scoring systems
      have been created and validated, and previous standardization of ANCA serologic
      and histologic analysis has been adopted. The systems of classification and
      clinical management described herein represent the recommendations of a
      multidisciplinary study group that hopes to improve the outcome of patients with
      primary systemic vasculitis by wide dissemination of the collective experience
      from interested centers.

PMID- 9276604
TI  - Hypercalcemia in a patient with hypoparathyroidism and Nocardia asteroides
      infection: a novel observation.
AB  - Hypercalcemia is associated with numerous chronic granulomatous processes and
      chronic infections. Increased production of 1,25-dihydroxyvitamin D by activated
      macrophages has been shown to be the cause in most cases. In this article, we
      describe a case of hypercalcemia related to infection with Nocardia asteroides.
      In a 34-year-old woman who previously had hypocalcemia, acute hypercalcemia
      developed coincident with Nocardia pericarditis. The hypercalcemia resolved after
      treatment of N. asteroides with sulfisoxazole. Parathyroid hormone and phosphorus
      levels were within normal limits, and total 25-hydroxyvitamin D levels were only
      mildly increased. After successful treatment of the Nocardia infection, the
      patient required supplemental calcium and vitamin D. Her hypercalcemia was
      temporally related to the duration of the N. asteroides infection. We believe
      this is the first reported case of hypercalcemia associated with N. asteroides
      infection.

PMID- 9276606
TI  - Rational clinical immunotherapy for multiple sclerosis.
AB  - In this article, we assess the roles and the efficacy of immunopharmacologic
      agents in the treatment of multiple sclerosis (MS) and other demyelinating
      disease syndromes. The initial clinical manifestations of demyelinating disease,
      immunotherapeutic goals, efficacy of individual agents, and specific
      immunopharmacologic recommendations are discussed. MS and other idiopathic
      demyelinating disease syndromes can be effectively managed with immunotherapy.
      Exacerbations are treatable, and the frequency and severity of exacerbations can
      be reduced. Although some agents have a minor effect on progression of
      disability, current approaches have not proved to have a major influence on
      treatment of progressive MS. Immunotherapy for inflammatory demyelinating disease
      necessitates a high degree of clinical certainty about the diagnosis. Because all
      available therapeutic agents have limitations and significant toxic effects,
      careful consideration is necessary before use. Treatment should be individualized
      on the basis of the clinical course of the disease and the degree of patient
      disability.

PMID- 9276605
TI  - Breast cancer in a man with human immunodeficiency virus infection.
AB  - Non-acquired immunodeficiency syndrome (AIDS)-defining neoplasms are being
      increasingly recognized in patients infected with the human immunodeficiency
      virus (HIV). The incidence of Hodgkin's disease and seminoma has recently been
      reported to be increasing in these patients. This article describes the second
      case of breast cancer in an HIV-infected male patient. A total of 11 cases of
      coincident breast cancer and HIV infection have previously been reported. It may
      be prudent to consider breast cancer in the differential diagnosis of an axillary
      mass in an HIV-infected patient.

PMID- 9276607
TI  - 80-year-old woman with dizziness.

PMID- 9276608
TI  - Understanding suffering: what palliative medicine teaches us.

PMID- 9276609
TI  - Sputum screening by quantitative microscopy: a new dawn for detection of lung
      cancer?

PMID- 9276610
TI  - Optic nerve sarcoidosis.

PMID- 9276612
TI  - Lymphoscintigraphic studies in patients with lymphedema.

PMID- 9276611
TI  - Liver failure due to metastatic small-cell carcinoma of the lung.

PMID- 9276613
TI  - Regeneration versus neoplastic growth.
AB  - Amphibian tissues seem to resist oncogenesis in proportion to their regenerative
      capacity, a phenomenon most easily seen in relation to limb regeneration. There
      is evidence that mammalian tissues also possess, in addition to and distinct from
      the capacity for physiological renewal, a limited and not always overtly evident
      degree of amphibian-like capacity for regeneration (epimorphic regeneration). It
      is the thesis of this paper that cancer in mammals would seldom occur were it not
      for a local destruction or exhaustion, secondary to injury or aging, of this
      normal amphibian-like regenerative capacity.

PMID- 9276614
TI  - Silent and multiple mutations in p53 and the question of the hypermutability of
      tumors.
AB  - Published data on TP53 mutations can be used to examine the question of whether
      generalized hypermutability is a necessary condition for tumorigenesis. Although
      individual mutations do play an etiologic role in tumor formation, the evidence
      so far does not make it necessary to assume a general mutability. Silent and
      multiple mutations in the TP53 data set indicate that a special hypermutability
      process operates on this gene during the generation of tumors. The percentage of
      silent p53 mutations observed (3%) is at least 20 times greater than would be
      expected and indicates hypermutability for this gene. The greater proportion of
      silent mutations among multiple p53 mutations (10%) indicates that the mutations
      occur nonselectively. The presence of silent mutations implies that not all
      mutations observed in tumors have an etiologic role. Analysis of the distribution
      of tumors with two, three, four and more p53 mutations suggests that mutations in
      some tumors occur in clusters possibly as a result of 'stuttering' in DNA
      synthesis. It is argued that the most likely alternative explanations of the
      data, polymorphism and/or a selective role for silent mutations, are not correct.
      It remains possible that the hypermutability process is restricted to particular
      genes or to regions of the genome as, for example, in antibody production. There
      is a surprising paucity of data on human polymorphism and nucleotide diversity
      which makes the analysis difficult.

PMID- 9276615
TI  - Kupffer cells are causally responsible for the mitogenic effect of peroxisome
      proliferators.
AB  - WY-14,643 [4-chloro-6-(2,3-xylidino)pyrimidinylthio-acetic acid] is a well-known
      non-genotoxic carcinogen and peroxisome proliferator that causes liver cancer in
      rodents by unknown mechanisms. Its ability to sustain elevated rates of
      hepatocyte DNA synthesis is most likely pivotal in the ultimate development of
      tumors. The source of this mitogenic stimulus following treatment of rats with WY
      14,643 has been hypothesized to be Kupffer cells, the resident hepatic
      macrophages, since they are activated by peroxisome proliferators in vivo.
      Therefore, these studies were designed to determine if Kupffer cells are causally
      responsible for WY-14 643-induced increases in hepatocyte DNA synthesis in vivo.
      WY-14,643 (100 mg/kg) increased DNA synthesis 8-fold 24 h after treatment;
      however, inactivation of Kupffer cells with methyl palmitate, a nonhydrolyzable
      fatty acid ester and known Kupffer cell inhibitor, completely prevented the
      mitogenic effect of WY-14,643. On the other hand, the ability of WY-14,643 to
      induce peroxisomes was not affected by methyl palmitate. These data demonstrate
      that induction of peroxisomes is not dependent on factors from Kupffer cells and
      support the idea that stimulation of DNA synthesis and induction of peroxisomes
      occur via distinct mechanisms. Additionally, WY-14,643 increased liver mRNA
      transcripts of the hepatocyte mitogen tumor necrosis factor alpha (TNF alpha)
      more than twofold. This increase was also prevented by inactivating Kupffer cells
      with methyl palmitate. Therefore, it is concluded that Kupffer cells are causally
      responsible for WY-14,643-induced increases in hepatocyte DNA synthesis most
      likely by increasing production of TNF alpha, a hepatic mitogen.

PMID- 9276616
TI  - 32P-Postlabelling of DNA adducts formed by allyl glycidyl ether in vitro and in
      vivo.
AB  - 32P-Postlabelling analysis of allyl glycidyl ether-treated DNA after adduct
      enrichment on anion-exchange cartridges revealed two major and one minor DNA
      adducts. The major adducts were shown to originate from alkylation at N-7-guanine
      and N-1-adenine, respectively, while the minor adduct was at N-3-cytosine. In
      addition, rearrangement products of the 1-adenine and 3-cytosine adducts to N6
      adenine and 3-uracil were indicated. The relative amounts of adenine, cytosine
      and uracil products appeared to be dependent upon conditions (in particular pH)
      during sample processing and analysis. When nuclease P1 was used for adduct
      enrichment the adenine, cytosine and uracil adducts, but not the 7-guanine
      adduct, were detected. The labelling efficiency of the 7-guanine adduct standard
      was 40-45%. Total recovery of this adduct from allyl glycidyl ether-modified DNA
      was 9-12%. The labelling efficiency of the 1-adenine adduct standard was 78-82%.
      Total recovery of this adduct from DNA was approximately 20% when using anion
      exchange chromatography for adduct enrichment and 30-34% when using nuclease P1.
      Preliminary analysis of DNA from mice treated with allyl glycidyl ether indicated
      57 times higher level of the 7-guanine adduct, per unit dose, in skin DNA (120
      per 10(8) normal nucleotides) after topical application when compared to liver
      DNA after i.p. administration. The 1-adenine adduct could not be quantified in
      liver DNA (due to an interfering background product present in untreated animals)
      and the level of the 3-cytosine adduct was below the detection limit of the
      method. After topical application the level of the 1 adenine adduct in skin DNA
      was approximately 30 per 10(8), using either column or nuclease P1 enrichment.
      The 3-cytosine adduct was detected in skin, but was not quantified.

PMID- 9276617
TI  - Characterization of two different cytoplasmic protein tyrosine kinases from human
      breast cancer.
AB  - Two different protein tyrosine kinases were detected in the cytosolic fraction of
      different human tumor tissues. After partial purification, the two enzymes, which
      were highly active in breast tumor tissues, were characterized. One of them,
      soluble tyrosine kinase-1 (STK-1), represents a soluble form of the c-Src
      protein, which is apparently underphosphorylated on its C-terminal tyrosine
      residue whereas the other (STK-2) is a 48-kDa protein tyrosine kinase (PTK),
      which is molecularly and functionally related to the C-terminal Src kinase (Csk).
      These two protein tyrosine kinases clearly exhibit a different substrate
      specificity, and are responsible for the high tyrosine kinase activity present in
      the cytosolic fraction of human breast cancer. In addition, it was observed that
      STK-1 and STK-2 are also expressed in the breast cancer cell line, CAL-51.

PMID- 9276619
TI  - Induction of esophageal tumors in zinc-deficient rats by single low doses of N
      nitrosomethylbenzylamine (NMBA): analysis of cell proliferation, and mutations in
      H-ras and p53 genes.
AB  - Dietary zinc deficiency in rats induces hyperplasia in the esophagus and
      increases N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumor incidence.
      Previous work showed a direct relationship between epithelial cell proliferation
      and esophageal tumor incidence in rats given multiple doses of NMBA. We
      investigated the effects of single low doses of NMBA in zinc-deficient rats since
      a single dose of 5.0 mg/kg was reported to be non-carcinogenic in rats. Zinc
      sufficient and deficient rats received a single i.g. dose of NMBA at 0.5 or 2.0
      mg/kg. At week 14, tumor incidence was 50% with 0.8 +/- 1.0 tumors/rat, and 80%
      with 2.2 +/- 1.9 tumors/rat, in deficient groups, D(0.5) and D(2.0), that
      received the lower and higher dose, respectively. In addition, two small
      papillomas were found in one out of eight untreated zinc-deficient rats. None of
      the NMBA-treated or untreated zinc-sufficient rats had any tumors. Esophageal
      cell proliferation, as determined by proliferating cell nuclear antigen (PCNA)
      immunohistochemistry, showed that, irrespective of NMBA treatment, deficient
      esophagi had significant increases in the number of labeled cells, the total
      number of cells, and the labeling index, as compared with zinc-sufficient ones.
      Mutations in Ha-ras and p53 genes in esophageal tumors were detected by single
      strand conformation polymorphism (SSCP) analysis. DNA sequencing of variant
      conformers revealed a point mutation (GGA-->GAA, codon 12) in Ha-ras in 4/5 (80%)
      and 5/8 (63%) tumors, from D(0.5) and D(2.0) rats, respectively. Three out of
      eight tumors from D(2.0) rats exhibited SSCP mobility shifts within p53 exons 5
      and 7: two tumors (2/8, 25%) had missense mutations and the third, a silent
      mutation. Of the two tumors with p53 mutations, one had a double mutation
      (transition at codon 164, TCA-->TTA; transversion at codon 241, AGT-->TGT), and
      the other tumor, a transition at codon 172 (AGA-->GGA), with amino acid changes
      in all cases. In parallel with PCNA expression, elevated p53 expression was
      associated with hyperplastic and dysplastic regions, as well as with tumors, in
      deficient esophagi. In short, these data indicate that dietary zinc deficiency,
      with its associated sustained increased cell proliferation in the esophagus, can
      drive an otherwise non-tumorigenic dose of NMBA into a highly tumorigenic one.

PMID- 9276618
TI  - Skin abnormality in aged fyn-/- fak+/- mice.
AB  - Focal adhesion kinase (FAK) is a novel non-receptor protein tyrosine kinase
      implicated in transducing signals from cell surface receptors. Its association
      with Fyn, a member of the Src family of tyrosine kinases, has been observed in
      cell lines. To examine in vivo the interaction between these two proteins, Fyn
      deficient mice were bred with fak heterozygous mutants (Fak deficiency is
      embryonic lethal). A majority of animals with the double mutation (fyn-/- fak+/-)
      displayed a transient impairment in thymocyte development at four weeks of age.
      However, all of them developed skin abnormalities at the age of 8-12 months. The
      most prominent among abnormalities was a greatly increased number and size of
      sebaceous glands. Also, the epidermis was thickened and hyperkeratotic. These
      observations would suggest involvement of Fyn and FAK in keratinocyte
      differentiation.

PMID- 9276620
TI  - Reversibility and apoptosis in rat urinary bladder papillomatosis induced by
      uracil.
AB  - Apoptosis is a morphologically and biochemically distinct form of cell death
      which determines specific patterns of tissue size and shape and balances cell
      proliferation. In the present study, the sequence of cellular proliferative
      alterations in urinary bladder epithelium associated with uracil-induced
      reversible urinary calculi was investigated in male F344 rats. Group 1 consisted
      of 45 rats, 6 weeks old at commencement of the experiment, which were given a
      diet containing 3% uracil for 8 weeks and were then returned to basal diet until
      week 20. Five rats were killed at each of weeks 2, 4, 8, 9, 10, 11, 12, 14 and
      20. Group 2 consisted of 15 rats which were given basal diet for 20 weeks. Five
      rats were killed at each of weeks 0, 8 and 20. Microscopic, reversible
      papillomatosis, which showed papillary projections of epithelial proliferation,
      was seen in the urinary bladder of all rats in group 1 through week 8. No
      epithelial lesions were apparent in any of rats in group 2. Anti-Le(y)(BM
      1/JIMRO)-positive areas of the urinary bladder epithelia were
      immunohistochemically seen in all rats of group 1 at weeks 2-12. At week 9 the
      percentage of anti-Le(y)-positive areas reached a maximum. Nick-end labeling
      stained nuclei of cells in the urinary bladder epithelium were observed in all
      rats of group 1 at weeks 4-14. At week 10 the labeling index was at a maximum.
      Proliferating cell nuclear antigen (PCNA)- and cyclin D1-positive cells of the
      urinary bladder epithelium were observed in group 1 at weeks 2, 4 and 8, however,
      at week 9 there were no PCNA- and cyclin D1-positive cells. In urinary bladder
      papillomatosis the simultaneous existence of apoptotic cells and proliferating
      cells was shown by double staining with anti-Le(y) (BM-1/JIMRO) and for PCNA. At
      week 10 apoptosis, stained by BM-1 and nick-end labeling, occurred extensively in
      regressing urinary bladder papillomatosis. Agarose gel electrophoresis of DNA in
      regressing papillomatosis at week 9 showed DNA fragmentation. Thus, these results
      indicate that apoptosis occurs in the process of papilloma regression following
      withdrawal of uracil treatment.

PMID- 9276622
TI  - Truncal site and detoxifying enzyme polymorphisms significantly reduce time to
      presentation of further primary cutaneous basal cell carcinoma.
AB  - Basal cell carcinoma (BCC) is the commonest cancer in Caucasians. Its incidence
      is rising and many patients develop multiple primary tumours at separate sites.
      Factors determining time between first primary tumour presentation and the next
      new primary lesion are unclear. We used Cox's proportional hazards model to
      study, in 856 Caucasians, the influence of tumour site, individual
      characteristics and polymorphism in glutathione S-transferase (GSTM1, GSTT1) and
      cytochrome P450 (CYP2D6, CYP1A1) loci on time to next primary tumour
      presentation. More than one tumour at first presentation (P <0.0001, hazard ratio
      2.72) and GSTT1 null (P = 0.028, hazard ratio 1.74) were associated with
      decreased time to next primary tumour presentation. Significant two-factor
      interactions, corrected for number of tumours at presentation, were identified
      between a truncal tumour at first presentation and each of male gender, GSTM1
      null and CYP2D6 EM (P <0.003, hazard ratios 3.09-3.82). In each of these cases,
      all patients with the risk combination demonstrated further separate tumours
      within 5 years of first presentation. Thus, patients with a truncal tumour at
      first presentation, especially males and those presenting with more than one
      lesion have a significantly decreased time to presentation of further tumours and
      should receive more meticulous follow-up. Polymorphism in GSTM1 and CYP2D6 also
      influences the rate of new primary tumour accrual giving insights into the link
      between ultraviolet exposure and multiple tumour development.

PMID- 9276621
TI  - Hepatic zonation of the induction of cytochrome P450 IVA, peroxisomal lipid beta
      oxidation enzymes and peroxisome proliferation in rats treated with
      dehydroepiandrosterone (DHEA). Evidence of distinct zonal and sex-specific
      differences.
AB  - Dehydroepiandrosterone (DHEA) is an intermediate product in the synthesis of male
      and female sex hormones in the adrenal cortex of man. In livers of rats and mice
      DHEA increases the levels of cytochrome P450 IVA and peroxisomal beta-oxidation
      enzymes associated with peroxisome proliferation. Prolonged treatment of rats
      with DHEA induces liver tumors that are more frequent in females arising mainly
      in the periportal regions of the liver lobule (Metzger et al., Toxicol. Pathol.
      23, 591-605, 1995). Because of paucity of information on hepatic zonation of
      peroxisomal response to DHEA and controversial reports on gender-specific
      differences of its effects the present study was undertaken using qualitative
      immunohistochemical and quantitative immunoelectron microscopical techniques in
      addition to Western blotting. Rats were treated for 24 weeks with 0.6% DHEA
      supplied with diet. Immunoblot analysis revealed marked induction of peroxisomal
      beta-oxidation enzymes, which by quantitative analysis was equally strong in male
      and female animals, whilst catalase and urate-oxidase were not increased.
      Cytochrome P450 IVA, in contrast, was induced significantly stronger in male than
      in female rats. Immunohistochemistry confirmed the induction of cytochrome P450
      IVA showing a marked lobular gradient in female animals with strong induction in
      pericentral and almost no induction in periportal regions of the liver lobule. In
      male animals cytochrome P450 IVA was expressed more uniformly across the liver
      lobule. A similar sex specific zone-dependent response was observed for
      peroxisomes. DHEA induced in females a significant zonal gradient with marked
      peroxisome proliferation and a strong induction of peroxisomal
      hydratase/dehydrogenase in pericentral hepatocytes and a much smaller response in
      periportal regions. Livers of male animals, in contrast, showed a uniform
      peroxisomal proliferation to DHEA with only slight zonal differences. The
      striking homologies of the induction patterns of cytochrome P450 IVA and the
      peroxisome proliferation in both sexes support the notion of a functional
      relationship. In view of the almost exclusive periportal localization of DHEA
      induced tumors in female rats in contrast to the pericentral localization of the
      peroxisomal proliferation shown by this study, it seems likely that other factors
      in addition to peroxisome proliferation may contribute to the hepatocarcinogenic
      effect of DHEA.

PMID- 9276623
TI  - Suppression of testosterone and estradiol-17beta-induced dysplasia in the
      dorsolateral prostate of Noble rats by bromocriptine.
AB  - We, and others, have previously described the histological changes that occur in
      the prostate gland of intact Noble (NBL) rats following prolonged hormonal
      treatment. Dysplasia, a pre-neoplastic lesion, develops specifically in the
      dorsolateral prostates (DLPs) of NBL rats treated for 16 weeks with a combined
      regimen of testosterone (T) and estradiol-17beta (E2) (T + E2-treated rats).
      Concurrent with DLP dysplasia induction, the dual hormone regimen also elicits
      hyperprolactinemia, in addition to an elevation of nuclear type II estrogen
      binding sites (type II EBS), no alteration in estrogen receptors (ER), and marked
      epithelial cell proliferation in the dysplastic foci. The aim of this study was
      to investigate whether the dual hormone action is mediated via E2-induced
      hyperprolactinemia. Bromocriptine (Br), at a dose of 4 mg/kg body wt per day, was
      used to suppress pituitary prolactin (PRL) release. Serum PRL levels were lowered
      from values of 341 +/- 50 ng/ml in T + E2-treated rats to 32 +/- 10 ng/ml in Br
      co-treated animals. The latter values were comparable to those in untreated
      control rats. In addition, Br co-treatment effectively inhibited the evolution of
      dysplasia (six out of eight rats) and the often associated inflammation (five out
      of eight rats) in most animals. In contrast, Br co-treatment did not suppress the
      T + E2-induced type II EBS elevation nor alter ER levels in the DLPs of these
      rats, when compared with T + E2-treated rats. These data extend the many previous
      studies that have detailed marked influences of PRL on rat prostatic functions.
      However, the current study is the first to implicate PRL in prostatic dysplasia
      induction in vivo.

PMID- 9276624
TI  - Inhibition of WY-14,643 induced hepatic lesion growth in mice by rotenone.
AB  - The effect of rotenone treatment on [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]
      acetic acid (WY-14,643) hepatic lesion growth in male B6C3F1 mice was
      investigated. Following induction of hepatic focal lesions by diethylnitrosamine
      (DEN) 35 mg/kg twice a week for 8 weeks, mice were placed into one of the four
      treatment groups: group I, control NIH-07 diet (control diet), group II, rotenone
      (600 mg/kg diet), group III NIH-07 diet containing WY-14,643 (1000 mg/kg diet),
      and group IV, NIH-07 diet containing WY-14,643 (1000 mg/kg diet) and rotenone
      (600 mg/ kg diet). Mice were killed after 30 and 60 days of dietary treatment.
      The effect of treatment with WY-14,643 and rotenone on hepatic lesion growth was
      examined by estimating the number of focal lesions per liver and the relative
      volume of focal lesions. WY-14,643 (group III) increased both the number and the
      volume of focal lesions. In particular, an increase in number and volume of
      basophilic lesions was seen. Co-treatment with WY-14,643 and rotenone (group IV)
      decreased both the number and the volume of the total number of focal lesions and
      basophilic foci compared with WY-14,643 treatment alone (group II). Alterations
      in the growth of hepatic focal lesions was further investigated by examining DNA
      synthesis and apoptosis within individual lesions. WY-14,643 (group III)
      treatment increased the DNA synthetic labeling index in all foci. Co-treatment of
      rotenone and WY-14,643 (group IV) decreased focal DNA synthesis and mitosis and
      increased the incidence of apoptotic hepatocytes. These data suggest that
      rotenone's ability to inhibit WY-14,643-induced hepatic focal lesion growth was
      mediated through a decrease in hepatic focal proliferation and an increase in
      focal apoptosis.

PMID- 9276625
TI  - Effect of naturally occurring coumarins on the formation of epidermal DNA adducts
      and skin tumors induced by benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene in
      SENCAR mice.
AB  - Several naturally occurring coumarins previously found to be potent inhibitors of
      mouse hepatic ethoxyresorufin-O-deethylase (EROD) and/or pentoxyresorufin-O
      dealkylase (PROD) were examined for their effects on formation of benzo[a]pyrene
      (B[a]P) and 7,12-dimethylbenz[a]anthracene (DMBA) DNA adducts in mouse epidermis,
      as well as, their effects on skin tumor initiation by these polycyclic aromatic
      hydrocarbons (PAH). Bergamottin, a potent inhibitor of hepatic EROD, given
      topically 5 min prior to an initiating dose of B[a]P, significantly decreased
      total covalent binding of B[a]P to DNA in a dose-dependent manner 24 h after
      treatment. A dose of 400 nmol bergamottin reduced covalent binding of B[a]P by
      72%. Coriandrin, at a dose of 400 nmol also significantly reduced total covalent
      binding of B[a]P by 59%. In addition, formation of the major (+)anti-B[a]P-diol
      epoxide-N2-dGuo adduct was selectively reduced by both of these coumarins. In
      contrast, bergamottin and coriandrin did not significantly decrease covalent
      binding of DMBA to epidermal DNA at doses of either 400 nmol or 800 nmol.
      Imperatorin and isopimpinellin, which are more potent inhibitors of hepatic PROD
      activity, significantly reduced overall binding of DMBA to epidermal DNA by 67%
      and 52%, respectively, when applied at doses of 400 nmol. These two coumarins
      also inhibited B[a]P-DNA adduct formation at similar doses but to a lesser
      extent. Imperatorin at a dose of 400 nmol dramatically decreased formation of
      covalent DNA adducts derived from both the anti and syn diol epoxides of DMBA.
      Bergamottin was a potent inhibitor of tumor initiation by B[a]P while coriandrin
      was less effective in this regard. Imperatorin was an effective inhibitor of skin
      tumor initiation by DMBA and also inhibited complete carcinogenesis by this PAH.
      At dose levels higher than those effective against DMBA, imperatorin also
      inhibited tumor initiation by B[a]P. The results demonstrate that several
      naturally occurring coumarins possess the ability to block DNA adduct formation
      and tumor initiation by PAHs such as B[a]P and DMBA. The mechanism for reduced
      DNA adduct formation and tumor initiation appears to involve inhibition of the
      P450s involved in the metabolic activation of these hydrocarbons. Finally, the
      differential effects of certain coumarins on B[a]P vs DMBA DNA adduct formation
      and tumor initiation may be useful for dissecting the role of specific
      cytochromes P450 in their metabolic activation.

PMID- 9276626
TI  - Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms and lung cancer
      risk among Northwestern Mediterraneans.
AB  - Several polymorphic genes including those encoding for glutathione S-transferases
      (GST) have been reported to be involved in modifying lung cancer risk in smokers.
      The gene GSTM1 is frequently deleted in humans and a possible association between
      the null genotype and lung cancer risk is controversial. Another polymorphic gene
      of the same supergene family, GSTT1, is also involved in the detoxification of
      some environmental carcinogens. Both genes were genotyped in (a) a group of lung
      cancer patients (n = 160); (b) a group of healthy smokers (n = 120); (c) a group
      of blood donors from the general population (n = 192). All patients and controls
      were Northwestern Mediterranean Caucasians. The results show that the GSTM1 null
      genotype (GSTM1*0/GSTM1*0) was slightly over represented in the lung cancer
      patients (frequency of 58%; OR: 1.40, 95% CI: 0.74-2.61, referred to healthy
      smokers). The histological type most clearly modified was small cell carcinoma
      (frequency of 62.2%, OR: 1.91, CI: 0.78-4.69). The subdivision of the patients
      with one or two copies of the GSTM1 gene according to a GSTM1*A, GSTM1*B or
      GSTM1*A/B genotype (frequencies of 28.2%, 11.2%, 2.5% respectively) revealed no
      significant differences between the cases and both control groups. The frequency
      of the deleted GSTT1 genotype among the lung cancer patients (24%) was not
      significantly increased (OR: 1.08, CI: 0.57-2.05, referred to healthy smokers).
      The results showed that 14.4% of the patients presented homozygous deletion of
      both GSTT1 and GSTM1 (12.5% among healthy smokers) suggesting no potentiation
      between null genotypes for lung cancer risk.

PMID- 9276627
TI  - Influence of diets containing high and low risk factors for colon cancer on early
      stages of carcinogenesis in human flora-associated (HFA) rats.
AB  - Germ-free rats colonised with a human intestinal flora were fed diets containing
      high risk (HR) or low risk (LR) factors for colorectal cancer, and putative
      biomarkers were evaluated in the colonic mucosa; (i) proliferation, (ii) 1,2
      dimethylhydrazine (DMH)-induced aberrant crypt foci and (iii) DMH-induced DNA
      damage. The HR diet was high in fat (45% of calories) and low in calcium and
      fibre, reflecting levels characteristic of typical western diets. The LR diet was
      low in fat (<5% of calories), and high in calcium and fibre. The nutrient/energy
      ratio of the two diets were similar. Mucosal crypt cell proliferation, assessed
      after microdissection, was higher on the LR diet (mean number of mitoses per
      crypt was 2.65 on the LR diet, and 1.62 on the HR diet; P < 0.05). Aberrant crypt
      foci (ACF) were assessed in the mucosa 12 weeks after DMH treatment. On the HR
      diet there were significantly more small ACF with 1 and 2 crypts per focus, but
      fewer ACF with 3, 5 and 7 or more crypts per focus. There was no significant
      difference in total ACF or the total number of crypts. The effect of diet on DNA
      damage in the colon was assessed in vivo by the comet assay. Animals were fed a
      HR or LR diet for 12 weeks before treatment with DMH or saline. For carcinogen
      treated animals, DNA damage was significantly higher in colon cells from animals
      on the HR diet. On the LR diet both DNA damage and the induction of small ACF
      were reduced despite an increase in cell proliferation. The increase in large ACF
      on the LR diet may be attributable to elevated crypt cell proliferation possibly
      increasing crypt fission rates.

PMID- 9276628
TI  - Inhibition of cdk2 kinase activity by methylselenocysteine in synchronized mouse
      mammary epithelial tumor cells.
AB  - Methylselenocysteine (MSC), an organic selenium compound has significant
      anticarcinogenic activity against mammary tumorigenesis. Previous experiments
      have demonstrated that MSC and inorganic selenite inhibit mammary cell (TM6 cell
      line) growth through different pathways. The present investigation demonstrated
      that MSC arrested cells in S phase during the TM6 cell cycle, which was followed
      by cells entering apoptosis at 48 h. Methylselenocysteine specifically affected
      the cdk2 kinase activity of the TM6 cells (54% reduction) at 16 h after release
      from growth arrest. The cdk4 kinase activity did not change during the cell
      cycle, confirming that cells had passed the G1 checkpoint and had entered S
      phase. The amount of cyclin E associated with cdk2 was increased by MSC by the 12
      h time point, thereby facilitating entry of cells into S phase. Afterwards,
      cyclin E and cyclin A associated with cdk2 did not change for the remainder of
      the cell cycle. The data demonstrate that inhibition of mammary cell growth by
      MSC is mediated by alterations in progression of cells through S phase. The
      decrease in cdk2 kinase activity is coincident with prolonged arrest in S phase.
      One consequence of prolonged arrest may be apoptosis.

PMID- 9276629
TI  - Melatonin and colon carcinogenesis: I. Inhibitory effect of melatonin on
      development of intestinal tumors induced by 1,2-dimethylhydrazine in rats.
AB  - The effect of pineal indole hormone melatonin on colon carcinogenesis was firstly
      studied in rats. Two-month-old outbred female LIO rats were weekly exposed to 15
      (experiment 1, groups 1 and 2) or to five (experiment 2, groups 1 and 2) s.c.
      injections of 1,2-dimethylhydrazine (DMH) at a single dose of 21 mg/kg of body
      weight. From the day of the first injection of the carcinogen DMH, the rats from
      groups 2 (experiments 1 and 2) were given melatonin five days a week during the
      night-time (from 18:00 h to 8:00 h), dissolved in tap water at 20 mg/l. The
      experiment was finalized in 6 months after the first injection of DMH. In both
      experiments the majority of tumors were localized in the descending colon. Tumors
      of the small intestines developed only in rats from experiment 1. Total incidence
      of colon tumors as well as tumors in different parts of the colon and the mean
      number of tumors per rat were much higher in rats from both groups in experiment
      1 than that in rats from experiment 2. In experiment 1 melatonin failed to
      influence the total incidence of colon tumors. However, incidence of carcinomas
      in the ascending colon was significantly reduced (P < 0.01). The multiplicity of
      total colon tumors per rat, as well as the mean number of tumors, ascending and
      descending colon per rat, was also decreased under the influence of melatonin
      (group 2 vs group 1, P < 0.01). In the same experiment, melatonin slightly
      decreased the depth of tumor invasion and increased number of highly
      differentiated colon carcinomas induced by DMH. The percentage of small tumours
      in the descending colon among rats from group 2 was higher than that of group 1.
      Treatment with melatonin was also followed by a decrease in the multiplicity of
      DMH-induced tumors of the duodenum (group 2 vs group 1, P < 0.05) and by a
      decrease in the incidence of jejunum and ileum tumors (group 2 vs group 1, P <
      0.05). In experiment 2, the inhibitory effect of melatonin on DMH-induced colon
      carcinogenesis was much more expressed than that in experiment 1. Thus, in group
      1 the incidence of total colon tumors, ascending and descending colon tumors, was
      significantly decreased in comparison with group 2; also melatonin reduced the
      number of tumors per rat in the ascending and descending colon. The number of
      colon tumors that invaded only mucosa was significantly higher in group 2 than in
      group 1, P < 0.05. The ratio of highly differentiated tumors was increased (P <
      0.05) and the ratio of low-differentiated tumors was decreased (P < 0.05) in rats
      exposed to melatonin (group 4) as compared with group 3. The number of large size
      tumors in the ascending and descending colon was decreased whereas the number of
      small size tumors (<10 mm2) was increased in those parts of the colon that were
      under the influence of melatonin in experiment 2. Thus, our results demonstrate
      the inhibitory effect of melatonin on intestinal carcinogenesis induced by DMH in
      rats.

PMID- 9276630
TI  - Excretion of DNA adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2
      amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline, PhIP-dG, PhIP-DNA and DiMeIQx-DNA
      from the rat.
AB  - The heterocyclic aromatic amines, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      (PhIP) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) are
      formed during frying of meat. PhIP and 4,8-DiMeIQx have, after metabolic
      activation, been shown to form adducts with DNA at the C8 of guanine both in
      vitro and in vivo. In order to investigate possible urinary biomarkers for
      estimation of the genotoxic dose of PhIP and 4,8-DiMeIQx, [3H]PhIP-dG, [3H]PhIP
      DNA and [14C]4,8-DiMeIQx-DNA were injected i.p. to rats and the excretion of
      radioactivity in urine and faeces were measured. For all three [3H]PhIP-dG,
      [3H]PhIP-DNA and [14C]4,8-DiMeIQx-DNA 15-20% of the dose were excreted in the
      urine and 80-85% of the dose were excreted in the faeces. Urinary excretion
      showed maximum to 24 h (90%) with a rapid decline, 10% to 48 h and 0% to 72 h.
      Faecal excretion also showed maximum to 24 h (60%) with a slower decline, 30% to
      48 h and 10% to 72 h. HPLC analysis of samples of urine and extracts from faeces,
      from rats dosed with [3H]PhIP-dG, showed that approximately 90% of the
      radioactivity co-eluted with PhIP-dG, indicating that PhIP-dG is excreted
      unmetabolized. HPLC analysis of samples of urine and extracts from faeces, from
      rats dosed with [3H]PhIP-DNA, showed that approximately 85% of the radioactivity
      co-eluted with PhIP-dG, indicating that PhIP-DNA adducts is mainly excreted as
      nucleoside adducts. Approximately 5% of the radioactivity excreted in the urine
      co-eluted with PhIP-G, indicating loss of deoxyribose. HPLC analysis of samples
      of urine and extracts from faeces, from rats dosed with [14C]4,8-DiMeIQx-DNA,
      showed that approximately 90% of the radioactivity co-eluted with 4,8-DiMeIQx-dG,
      indicating that 4,8-DiMeIQx-DNA adducts is mainly excreted as nucleoside adducts.
      Man is able to eliminate compounds of a higher mol. wt in the urine than the rat,
      the percentage of PhIP-dG and 4,8-DiMeIQx eliminated in the urine of man would
      therefore be expected to be higher than in the rat. Measurement of urinary
      nucleoside adducts of PhIP and 4,8-DiMeIQx could therefore provide a basis for
      the development of a biomonitoring strategy for the genotoxic dose of these food
      derived HAA.

PMID- 9276631
TI  - Nitrosated peptides and polyamines as endogenous mutagens in O6-alkylguanine-DNA
      alkyltransferase deficient cells.
AB  - Mutants of Escherichia coli and Saccharomyces cerevisiae that lack O6
      alkylguanine-DNA alkyltransferase activities have increased spontaneous mutation
      rates, indicating the presence of a cellular metabolite that can alkylate DNA.
      Bacterially catalysed nitrosation has been implicated previously in producing the
      endogenous alkylating agent(s). Here, nitrosated polyamines and azaserine, a
      model compound for nitrosated peptides, are shown to be mutagenic to E. coli ada
      ogt mutants deficient in O6-alkylguanine-DNA alkyltransferase activity. The
      mutagenicity of azaserine may be explained by its ability to methylate DNA,
      whereas nitrosated spermidine causes DNA damage that is susceptible to both
      nucleotide excision repair and O6-alkylguanine-DNA alkyltransferase activity,
      which indicates the generation of more bulky DNA adducts. Nitrosated peptides and
      polyamines are therefore potential endogenous mutagens that are harmful
      particularly in O6-alkylguanine-DNA alkyltransferase deficient cells.

PMID- 9276632
TI  - Altered processing of precursor transcripts and increased levels of the subunit I
      of mitochondrial cytochrome c oxidase in Syrian hamster fetal cells initiated
      with ionizing radiation.
AB  - Treatment of Syrian hamster fetal cells (SHFC) with ionizing radiation resulted
      in the establishment of 21 transformed cell lines. Relative to unirradiated
      controls, cells from early post-irradiation passages (p.3) showed marked
      morphologic alterations, increased growth rate and extended life span, and they
      were contact-inhibited and not tumorigenic in nude mice, although they became
      tumorigenic after extended passaging in culture (p. > 30). Differential mRNA
      display analyses of normal cells (84-3) and radiation-initiated cell lines at
      early passage showed that the latter contained increased steady-state levels of
      the precursor (4-fold) and mature (1.7-fold) transcripts of the mitochondrial
      (mt) gene encoding the subunit I of cytochrome c oxidase (CO I). These molecular
      alterations were consistently observed in 57% of the irradiated (HDR) cell lines,
      and were stably maintained during continuous passaging (p. > 50). Further
      analyses of one of these cell lines (HDR-3) demonstrated that the accumulation of
      CO I precursor transcripts was the result of mRNA stabilization and increased
      replication and/or amplification of the mt DNA. Radiation-initiated cells
      contained elevated levels of the CO I protein, showed a 75% reduction in
      cytochrome c oxidase (CO) activity, and a 5-fold increase in the concentration of
      hydrogen peroxide secreted into their culture medium compared with cells with no
      alterations in CO I mRNA processing. Our findings suggest that alterations in mt
      CO I processing may play a role in the neoplastic conversion of mammalian cells
      by ionizing radiation.

PMID- 9276634
TI  - Molecular modeling of the conformational complexity of (+)-anti-B[a]PDE-adducted
      DNA using simulated annealing.
AB  - Benzo[a]pyrene (B[a]P), a potent mutagen/carcinogen, reacts with DNA following
      metabolism to its corresponding (+)-anti-7,8-diol-9,10-epoxide [(+)-anti
      B[a]PDE], giving a major adduct (+)-trans-anti-B[a]P-N2-dG. Evidence suggests
      that this adduct is responsible for most of the different kinds of mutations
      (e.g. G-->T, G-->A, etc.) induced by (+)-anti-B[a]PDE, raising the question of
      how can a single adduct cause many different kinds of mutations? One hypothesis
      is that different mutations are induced depending upon the conformation of this
      adduct when bypassed during DNA replication. If true, then it becomes imperative
      to explore different reasonable conformations for this adduct. Herein a simulated
      annealing protocol is employed to study the conformation of (+)-trans-anti-B[a]P
      N2-dG with the B[a]P moiety in the minor groove and pointing toward the base on
      its 5'-side in a 5'-CGC-3' sequence context in duplex DNA. This conformation and
      sequence were chosen because there is a structure derived from NMR constraints
      for comparison. A four step procedure is followed: the adduct is docked in
      canonical B-DNA, after which the structure is subjected to an initial conjugate
      gradient minimization, followed by simulated annealing and a final conjugate
      gradient minimization. The quality and final energy of structures is assessed as
      a function of changes in six parameters, including the length of the DNA helix,
      the initial annealing temperature (T0), the annealing time (t), the molecular
      dynamics time step (tau) and two other parameters. While there is no single set
      of optimum parameters, reasonable low energy structures were obtained using the
      values t approximately 40 ps (or longer), T0 approximately 750 K and tau
      approximately 1.0 fs with a helix length of 7 bp. The structures that emerge all
      retain the basic features of the input structure, being B-DNA-like with the B[a]P
      moiety in the minor groove pointing toward the base on the 5'-side. However,
      within this broad category there are at least six subclasses of structures, of
      which four have lowest energy members that differ by < approximately 5 kcal/mol.
      The fact that a variety of distinct but related structures emerge from a single
      starting structure as this parameter set is varied suggests that the use of a
      large but manageable number of simulated annealing runs should be considered in
      the search for a cohort of related structures. This is especially important given
      that this breadth of potentially relevant structures of approximately the same
      energy may indeed be relevant to the hypothesis that different mutations arise
      from a single adduct in different conformations.

PMID- 9276633
TI  - Enzymes involved in the bioactivation of 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone in patas monkey lung and liver microsomes.
AB  - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent tobacco-specific
      carcinogen in animals. Our previous studies indicated that there are differences
      between rodents and humans for the enzymes involved in the activation of NNK. To
      determine if the patas monkey is a better animal model for the activation of NNK
      in humans, we investigated the metabolism of NNK in patas monkey lung and liver
      microsomes and characterized the enzymes involved in the activation. In lung
      microsomes, the formation of 4-oxo-1-(3-pyridyl)-1-butanone (keto aldehyde), 4
      (methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanone (NNK-N-oxide), 4-hydroxy-1
      (3-pyridyl)-1-butanone (keto alcohol), and 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanol (NNAL) was observed, displaying apparent Km values of 10.3, 5.4, 4.9, and
      902 microM, respectively. NNK metabolism in liver microsomes resulted in the
      formation of keto aldehyde, keto alcohol, and NNAL, displaying apparent Km values
      of 8.1, 8.2, and 474 microM, respectively. The low Km values for NNK oxidation in
      the patas monkey lung and liver microsomes are different from those in human lung
      and liver microsomes showing Km values of 400-653 microM, although loss of low Km
      forms from human tissue as a result of disease, surgery or anesthesia cannot be
      ruled out. Carbon monoxide (90%) significantly inhibited NNK metabolism in the
      patas monkey lung and liver microsomes by 38-66% and 82-91%, respectively.
      Nordihydroguaiaretic acid (a lipoxygenase inhibitor) and aspirin (a
      cyclooxygenase inhibitor) decreased the rate of formation of keto aldehyde and
      keto alcohol by 10-20 % in the monkey lung microsomes. Alpha-Napthoflavone and
      coumarin markedly decreased the oxidation of NNK in monkey lung and liver
      microsomes, suggesting the involvement of P450s 1A and 2A6. An antibody against
      human P450 2A6 decreased the oxidation of NNK by 12-16% and 22-24% in the patas
      monkey lung and liver microsomes, respectively. These results are comparable to
      that obtained with human lung and liver microsomes. Coumarin hydroxylation was
      observed in the patas monkey lung and liver microsomes at a rate of 16 and 4000
      pmol/min/mg protein, respectively, which was 5-fold higher than human lung and
      liver microsomes, respectively. Immunoblot analysis demonstrated that the P450 2A
      level in the individual patas monkey liver microsomal sample was 6-fold greater
      than in an individual human liver microsomal sample. Phenethyl isothiocyanate, an
      inhibitor of NNK activation in rodents and humans, decreased NNK oxidation in the
      monkey lung and liver microsomes displaying inhibitor concentration resulting in
      50% inhibition of the activity (IC50) values of 0.28-0.8 microM and 4.2-6.8
      microM, respectively. The results demonstrate the similarities and differences
      between species in the metabolic activation of NNK. The patas monkey microsomes
      appear to more closely resemble human microsomes than mouse or rat enzymes and
      may better reflect the activation of NNK in humans.

PMID- 9276635
TI  - Ovary-intact, but not ovariectomized female ACI rats treated with 17beta
      estradiol rapidly develop mammary carcinoma.
AB  - We have examined the ability of 17beta-estradiol (E2) to induce development of
      mammary cancers in the female ACI rat. Continuous treatment with E2, delivered
      through release from s.c. Silastic tubing implants containing 27.5 mg crystalline
      hormone, resulted in rapid development of palpable mammary tumors in ovary-intact
      ACI rats. In a population of 21 E2-treated rats, palpable tumors were first
      observed following 99 days treatment and 100% of the treated population developed
      tumors within 197 days. The median and mean times to appearance of first palpable
      tumor were 143 and 145 days respectively. All mammary tumors were classified as
      carcinomas and invasive features were observed. Circulating E2 levels in the
      treated animals at the time of sacrifice averaged 185 pg/ml serum. Mammary tumors
      were not observed in ovary-intact female ACI rats that were not treated with E2.
      This is the first report indicating that this naturally occurring estrogen is
      capable of inducing mammary cancers in the ACI rat strain. Mammary carcinoma did
      not develop in a population of 11 ovariectomized female ACI rats treated with E2
      for a period of 140 days. Circulating E2 levels in the treated ovariectomized
      animals averaged 207 pg/ml. These data indicate that the ovary modulates estrogen
      mediated mammary carcinogenesis in this rat strain. Both ovary-intact and
      ovariectomized female ACI rats displayed similar susceptibilities to E2-induced
      pituitary tumors and hyperprolactinemia. Pituitary weight was increased 6.0-fold
      in ovary-intact ACI rats and 5.3-fold in ovariectomized female rats. Circulating
      prolactin levels averaged 2318 ng/ml in E2-treated, ovary-intact rats and 2285
      ng/ml in E2-treated, ovariectomized ACI rats. These data indicate that estrogen
      induced hyperprolactinemia is not the sole factor leading to development of
      mammary cancers in the E2-treated ACI rat.

PMID- 9276636
TI  - Bioactivation of the mushroom hydrazine, agaritine, to intermediates that bind
      covalently to proteins and induce mutations in the Ames test.
AB  - The present study was undertaken to establish whether liver and kidney enzyme
      systems, from rat and mouse, have the potential to metabolise and bioactivate
      agaritine, beta-N-(gamma-L(+)glutamyl)-4-(hydroxymethyl)phenylhydrazine, the most
      abundant hydrazine present in the edible mushroom Agaricus bisporus. Agaritine
      was weakly mutagenic, in the absence of an activation system, in Salmonella
      typhimurium strain TA104. Rat kidney homogenates, characterised by high gamma
      glutamyl transpeptidase activity, enhanced the mutagenic response. In contrast,
      hepatic microsomes, having very low gamma-glutamyl transpeptidase activity, did
      not influence the mutagenicity of agaritine. However, hepatic microsomes could
      further potentiate the mutagenic response induced by the kidney. Agaritine was a
      good substrate for purified gamma-glutamyl transpeptidase, being converted to a
      major metabolite, 4-(hydroxymethyl)phenylhydrazine, formed as a result of the
      loss of the glutamyl moiety. Kidney homogenates from the rat and mouse also
      catalysed this reaction, the former being the more effective. Metabolism of
      agaritine was suppressed by serine-borate, an inhibitor of gamma-glutamyl
      transpeptidase. Kidney homogenates from rat and mouse could metabolise agaritine
      to intermediate(s) that bound covalently to proteins, with the rat preparations
      being the more effective; covalent binding was inhibited by glutathione. In
      contrast, hepatic preparations alone were ineffective in producing such covalent
      binding but did further increase the covalent binding mediated by the kidney
      preparations. It is concluded that rat and mouse kidney homogenates catalyse the
      removal of the glutamyl group from agaritine to yield the reactive free
      hydrazine, which is further converted to the highly reactive diazonium ion by
      hepatic microsomes.

PMID- 9276637
TI  - Sequence context is an important determinant in the mutagenic potential of 1,N6
      ethenodeoxyadenosine (epsilonA): formation of epsilonA basepairs and elongation
      in defined templates.
AB  - Many laboratories have obtained data on mutagenicity of modified bases in
      naturally occurring DNA sequences. It has often been noted that mutation is
      favored in certain sequence contexts, sometimes termed 'hot spots'. This approach
      to the contribution of neighboring sequences does not permit a systematic study
      of both the qualitative and quantitative mutational frequencies. In the present
      experiments we have chosen to use the exocyclic adduct, 1,N6-etheno A (epsilonA),
      site-specifically placed in a defined 25-mer oligonucleotides in which epsilonA
      is flanked by differing 5' and 3' tandem bases. Mutation was assessed using an in
      vitro replication assay and five polymerases of varying fidelity. The relevant
      central sequences were 3' --> 5' -CC-epsilonA-CC-, -GG-epsilonA-GG-, -TT-epsilonA
      TT-, -AA-epsilonA-AA-, -GG-epsilonA-TT-, -TT-epsilonA-AA-, -AT-epsilonA-TT- and 
      TA-epsilonA-TA-. Using the Klenow fragment (Kf) (exo+ or exo-) of E. coli Pol I,
      it was found the epsilonA is an ambiguous base and, with varying efficiencies,
      all four dNTPs could be inserted opposite epsilonA in all sequences. However,
      only 3' --> 5' -TT-epsilonA-TT-, -GG-epsilonA-TT- and -AT-epsilonA-TT- were fully
      extended to a significant extent. The only sequences essentially blocked at the
      position of epsilonA were -AA-epsilonA-AA- and -TT-epsilonA-AA-. The others were
      intermediate. When replication was performed with Sequenase, MMLV RT or HIV RT,
      different patterns were observed, in which replication terminated one base prior
      to epsilonA, at epsilonA, or one base after epsilonA without further extension.
      In favored sequences, using the Klenow fragment, an epsilonA x N pair could be
      extended to form normal basepairs. No extension could be demonstrated in
      sequences in which tandem adenines were 5' to epsilonA. Kinetic data showed that
      two of the epsilonA x N pairs, epsilonA x A and epsilonA x C, could form at 10
      microM or less dNTP. Which bases were preferentially inserted opposite epsilonA
      was a function of the flanking bases. Under the kinetic conditions used, epsilonA
      x T did not form even at 1 mM dTTP. These results indicate that the chemical
      structure of an adduct is not the only determinant of mutagenic efficiency. It is
      likely that the effect of the adduct on replication is due to the changes in the
      structural environment conferred by the flanking bases.

PMID- 9276639
TI  - Evidence for cytochrome P450 2A6 and 3A4 as major catalysts for N'
      nitrosonornicotine alpha-hydroxylation by human liver microsomes.
AB  - The tobacco specific carcinogen N'-nitrosonornicotine (NNN), is believed to be a
      causative agent for esophageal cancer in smokers. NNN requires metabolic
      activation to exert its carcinogenic potential. Metabolism occurs through
      cytochrome P450 (P450) catalyzed 2'- and 5'-hydroxylation, which generates
      unstable metabolites that decompose to 4-hydroxy-1-(3-pyridyl)-1-butanone ('keto
      alcohol') and 4-hydroxy-4-(3-pyridyl)butanal, respectively. The latter cyclyzes
      to 5-(3-pyridyl)-2-hydroxytetrahydrofuran ('lactol'). 2'-Hydroxylation of NNN is
      believed to be the pathway critical for esophogeal NNN carcinogenesis in the rat.
      The ability of human liver microsomes and expressed human P450s to metabolize [5
      (3)H]NNN to keto alcohol and lactol was determined by reverse phase HPLC with
      radioflow detection. At low NNN concentrations, 11 human liver microsomes
      metabolized NNN primarily by 5'-hydroxylation to lactol. This reaction was
      strongly correlated (r = 0.92) with coumarin 7-hydroxylation, suggesting that NNN
      5'-hydroxylation is catalyzed mainly by P450 2A6. 2'-Hydroxylation of NNN by
      human liver microsomes correlated with 6beta-hydroxylation of testosterone, a
      P450 3A4-specific activity (r = 0.94). The relative rates of 2'- and 5'
      hydroxylation by human P450s 2A6, 2E1, 2D6 and 3A4 expressed in Sf9 cells by the
      baculovirus-insect cell expression system, and human P450 3A4 produced by stable
      expression in Chinese hamster ovary cells, were determined. Human P450 2A6
      metabolized 1 microM NNN exclusively by 5'-hydroxylation. The rate of lactol
      formation was 317 pmol/min per nmol P450. Human P450s 2E1 and 2D6 also
      metabolized NNN only to lactol, but at much lower rates, 0.4 and 0.8 pmol/min per
      nmol of P450 respectively. In contrast, the metabolism of NNN by expressed human
      P450 3A4 was specific for keto alcohol formation. The Km for 5'-hydroxylation by
      baculovirus-expressed P450 2A6 was 2.1 microM, and k(cat) was 953 pmol/min per
      nmol of P450. The Km for lactol formation by human liver microsomes containing
      high levels of P450 2A6, was 5 microM . Human liver microsomes exhibited a Km of
      312 microM for keto alcohol formation. Coumarin, 8-methoxypsoralen (P450 2A6
      inhibitors), and anti-2A6 monoclonal antibody were strong inhibitors of NNN
      derived lactol formation in human liver microsomes. Troleandomycin, an inhibitor
      of P450 3A4, effectively inhibited the metabolism of NNN to keto alcohol by human
      liver microsomes. These results are consistent with P450 2A6 mediated 5'
      hydroxylation and P450 3A4 mediated 2'-hydroxylation of NNN in human liver
      microsomes.

PMID- 9276638
TI  - Inhibition of UVB induced DNA photodamage in mouse epidermis by topically applied
      alpha-tocopherol.
AB  - Ultraviolet B (UVB, 290-320 nm) exposure results in a variety of cellular insults
      including induction of cyclobutane pyrimidine dimers in DNA. Accumulation of
      these lesions can lead to mutations in critical genes and contribute to the
      development of nonmelanoma skin cancer. Topically applied alpha-tocopherol
      (vitamin E) has previously been shown to prevent the induction of skin tumors in
      UVB irradiated female C3H/HeNTac mice. We hypothesized that alpha-tocopherol,
      which absorbs strongly in the UVB, may act as a sunscreen to prevent photodamage.
      To explore possible mechanisms of photoprotection, we topically applied alpha
      tocopherol dispersed in a neutral cream vehicle to the dorsal epidermis of female
      C3H/HeNTac mice and exposed them to 2.5 J/m2/s of UVB for 60 min. Immediately
      after exposure, we analyzed thymine dimer levels in DNA by capillary gas
      chromatography with electron capture detection. Epidermal DNA from mice receiving
      this UVB dose contained 247 +/- 42 pmol thymine dimers/micromol thymine. Topical
      application of alpha-tocopherol inhibited dimer formation in a dose-dependent
      manner. A 1% alpha-tocopherol dispersion inhibited the formation of thymine
      dimers to 43% of levels in vehicle controls. Several vitamin E compounds,
      including alpha-tocopherol acetate, alpha-tocopherol methyl ether, gamma
      tocopherol, and delta-tocopherol also inhibited thymine dimer formation, but were
      five- to ten-fold less potent than alpha-tocopherol. A variety of commercially
      available sunscreens were also less potent than alpha-tocopherol in their ability
      to reduce dimer formation. These results suggest that DNA photoprotection is an
      important mechanism by which topically applied alpha-tocopherol can inhibit UVB
      induced skin cancer. Alpha-Tocopherol acetate, the most common form of vitamin E
      in commercial skin care products, conferred less protection, perhaps due to its
      lower absorptivity in the UVB. Our results further underscore the importance of
      determining which forms of vitamin E can inhibit specific lesions involved in
      photocarcinogenesis.

PMID- 9276641
TI  - Measurement of benzene oxide in the blood of rats following administration of
      benzene.
AB  - Although it is generally assumed that metabolism of benzene proceeds through an
      initial step involving oxidation to benzene oxide (BO) by CYP450 in the liver,
      the production of BO has never been unambiguously confirmed in animals dosed with
      benzene. Furthermore, prevailing hypotheses of the mechanism by which benzene
      causes cancer have ignored the possibility that BO might play a direct role,
      despite the fact that BO is electrophilic, binds covalently to cell
      macromolecules and is presumably genotoxic. A likely reason for this lack of
      attention to the role of BO in the carcinogenesis of benzene is the presumption
      that this epoxide is too reactive to escape the hepatocyte after it is formed. We
      employed gas chromatography-mass spectrometry to measure BO in the blood of F344
      rats, both in vitro and up to 24 h following oral administration of benzene.
      Surprisingly, BO was relatively stable in rat blood at 37 degrees C (estimated
      half-life = 7.9 min) and, after administering a single dosage of 400 mg
      benzene/kg body wt, a blood concentration of 90 nM BO (8.5 ng/ml) was measured
      for approximately 9 h. Using a published PBPK model we estimate that
      approximately 4.3% of the metabolized dose of benzene was released as BO from the
      liver into blood. This confirms that BO is, indeed, formed from metabolism of
      benzene and is sufficiently stable to be distributed throughout the body at
      levels which are likely to be greater than those of the other electrophilic
      benzene metabolites.

PMID- 9276640
TI  - High incidence of nitrosamine-induced tumorigenesis in mice lacking DNA repair
      methyltransferase.
AB  - The enzyme O6-methylguanine-DNA methyltransferase repairs alkylation-induced DNA
      damage, O6-methylguanine and O4-methylthymine, the former being formed more
      frequently. Previously, by means of gene targeting, we generated mice in which
      alleles for methyltransferase were disrupted. We now use these mouse lines, which
      are totally deficient in methyltransferase activity, to examine protective
      effects of the enzyme against tumor formation. In gene-targeted female mice given
      an i.p. injection of 5 mg/kg of dimethylnitrosamine, a larger number of liver and
      lung tumors occurred, as compared with normal female mice treated in the same
      manner. In male mice given a lower dose of carcinogen, the difference between
      normal and gene-targeted mice was statistically insignificant although more
      tumors did form in the gene-targeted mice. Methyltransferase apparently afforded
      protection from nitrosamine-induced tumorigenesis.

PMID- 9276642
TI  - Loss of response to epidermal growth factor and retinoic acid accompanies the
      transformation of human prostatic epithelial cells to tumorigenicity with v-Ki
      ras.
AB  - Growth factor-independent proliferation and loss of response to differentiation
      factors are believed to be critical elements in carcinogenesis. We have developed
      an in vitro model of human prostatic carcinogenesis by the introduction of SV40
      DNA into normal prostatic epithelial cells to create a transformed, immortal cell
      line, pRNS-1-1. This non-tumorigenic cell line responded similarly to normal
      prostatic epithelial cells to most growth- and differentiation-regulatory
      factors, with the notable exception of loss of response to the inhibitory factor
      1,25-dihydroxyvitamin D3. In this study, we describe the introduction of the ras
      oncogene into pRNS-1-1 cells to create a tumorigenic cell line, pRNS-1-1/ras. In
      addition to an attenuated response to 1,25-dihydroxyvitamin D3, these cells also
      became unresponsive to retinoic acid and gained the ability to undergo clonal
      proliferation in the absence of epidermal growth factor (EGF). EGF-independent
      growth could not be linked to the production of autocrine transforming growth
      factor-alpha, but instead was likely due to sustained signaling by the ras
      oncogene, bypassing ligand-activation of the EGF receptor. Ligand-independent
      proliferation, coupled with the loss of response to the growth-inhibitory and
      differentiation agent retinoic acid, may be important elements in the conversion
      of human prostatic epithelial cells to tumorigenicity.

PMID- 9276643
TI  - Effect of toxaphene on estrogen receptor functions in human breast cancer cells.
AB  - Toxaphene (polychlorinated camphenes) is an insecticidal mixture of >670
      chemicals, which was widely used until the mid 1980s. Due to their lipophilic and
      volatile nature, these chemicals accumulate in animal and human tissues and
      continue to be a major contaminant in marine and freshwater biota. Cytotoxic and
      genotoxic effects in mammalian test systems suggest that toxaphene is a
      carcinogen and reports support the hypothesis that toxaphene could have tumor
      promoting potential in human breast tissue. In order to examine the potential of
      toxaphene as an environmental endocrine disrupter, we investigated its effect on
      the estrogen receptor (ER) function in human breast cancer MCF-7 cells. Using
      transient gene expression experiments, we observed approximately 60% and 80%
      inhibition of the constitutive and 17beta-estradiol induced ER-dependent
      transactivation, respectively. The involvement of the ER in the ability of
      toxaphene to block the estrogen action was verified by cotransfection studies in
      ER-negative MDA-MB-231 cells. The interference of toxaphene with the ER mediated
      responses was supported by a significant suppression of endogenously expressed
      pS2 RNA and decreased levels of secreted pS2 protein. These reproducible results
      indicate that toxaphene can disturb hormonal signals mediated by the ER and
      suggest that these environmental chemicals have potential endocrine disrupting
      activities which may affect the reproductive health and increase the risk of
      carcinogenesis.

PMID- 9276644
TI  - Induction of the apoptosis-promoting protein Bak by perillyl alcohol in
      pancreatic ductal adenocarcinoma relative to untransformed ductal epithelial
      cells.
AB  - Perillyl alcohol has antitumor activity toward pancreas and other cancers with
      low toxicity. Here, we have investigated the mechanism of action responsible for
      the differential sensitivity of malignant versus non-malignant pancreatic cells
      to the drug. We report that the rate of apoptosis is over 6-fold higher in
      perillyl alcohol-treated pancreatic adenocarcinoma cells than in untreated cells,
      and that the effect of perillyl alcohol on pancreatic tumor cells is
      significantly greater than its effect on non-malignant pancreatic ductal cells.
      Moreover, the perillyl alcohol-induced increase in apoptosis in all of the
      pancreatic tumor cells is associated with a 2- to 8-fold increase in the
      expression of the proapoptotic protein Bak, but Bak expression is not affected by
      perillyl alcohol in non-malignant cells. Thus, the antitumor activity of perillyl
      alcohol toward pancreatic cancers may be due to preferential stimulation of Bak
      induced apoptosis in malignant versus normal cells. Bak may, therefore, be a
      useful biomarker for the chemopreventive and therapeutic effects of perillyl
      alcohol.

PMID- 9276645
TI  - Tobacco smoke, recurrences, and p53/bcl-2 expression in bladder cancer.
AB  - Overexpression of p53 is considered to be predictive of mutations of the p53
      gene. Exposure-specific mutations of the p53 gene have been described for cancers
      at different sites. An association between p53 mutation/overexpression and
      smoking has been described in early stage bladder cancer, but results were
      conflicting. We have conducted a study on 131 bladder cancer cases, considering
      p53 expression and smoking habits in an area where the use of air-cured tobacco,
      rich in carcinogenic arylamines, is common. The study suggests that the use of
      air-cured tobacco induces p53 overexpression (possibly via mutation) in early
      stage-low grade bladder cancer, more frequently than flue-cured tobacco (odds
      ratios = 3.4, 95% confidence intervals 0.9-13 in stage 1; odds ratios = 24, 95%
      confidence intervals 1.1-519 in stage 1, grade 1). However, all the excess
      associated with air-cured tobacco was concentrated in recurrences. When
      available, the biopsies of recurrent cases with early-stage disease were re
      examined and all showed p53 expression at first diagnosis (with 10-50% of cells
      positive) (n = 5). It is hypothesized that exposure to tobacco-related chemicals
      increases the risk of recurrences via p53 overexpression/mutation. Expression of
      the bcl-2 gene was detected in only 2 out of 13 p53-positive smokers.

PMID- 9276646
TI  - Focal nuclear hepatocyte response to oxidative damage following low dose
      thioacetamide intoxication.
AB  - Rats were treated with low doses of the hepatocarcinogen thioacetamide. Forty
      eight hours following this treatment, microscopic foci of hepatic injury were
      observed, which were surrounded by a peripheral rim of histologically normal
      hepatocytes. These peripheral hepatocytes generally contained enlarged nuclei,
      and showed nuclear staining for 4-hydroxynonenal-protein adducts, indicative of
      nuclear oxidative damage. In these same hepatocytes, we also observed specific
      focal nuclear induction of mu-class glutathione-S-transferase and alcohol
      dehydrogenase I, two enzymes which are important in metabolism of 4
      hydroxynonenal. Of particular interest was the concurrent nuclear induction of
      APE/ref-1, a multifunctional DNA repair enzyme which can function as a redox
      factor, and of the transcription factor Jun, whose DNA binding is facilitated by
      APE/ref-1. These results document an orchestrated focal nuclear response to
      oxidative damage produced by thioacetamide administration, and may relate to the
      permanent effects produced by this treatment.

PMID- 9276647
TI  - The plasticizer benzyl butyl phthalate (BBP) inhibits 7,12
      dimethylbenz[a]anthracene (DMBA)-induced rat mammary DNA adduct formation and
      tumorigenesis.
AB  - Although the risk for cancer is multifactorial, a substantial portion of cancer
      incidence rates is related to environmental factors, including diet and
      environmental chemicals. The magnitude of the contribution to cancer of the
      breast from exposure to environmental chemicals remains unclear. The phthalate
      ester plasticizers are abundantly-produced industrial chemicals that have become
      widely-dispersed environmental pollutants. The present studies were conducted to
      determine the effect of the phthalate ester, benzyl butyl phthalate (BBP) on
      mammary gland carcinogenesis induced in the female rat by the polycyclic aromatic
      hydrocarbon (PAH) 7,12-dimethylbenz[a]anthracene (DMBA). Exposure to BBP (i.p.
      injection) at 100 and 500 mg/kg doses for 5 days resulted in a significant 72 and
      92% inhibition, respectively, in the in vivo formation of mammary DMBA-DNA
      adducts, compared to controls. Treatment with BBP (i.g. intubation) for 7 days
      resulted in a significant (48%) inhibition in mammary DMBA-DNA adduct formation
      only for those animals receiving the 500 mg/kg dose, compared to controls.
      Administration of BBP (i.g.) at 500 mg/kg for 7 days also was associated with a
      significant 8.5-fold increase in the liver activity of 7-ethoxyresorufin-O
      deethylase. No change in liver glutathione-S-transferase activity was observed
      for animals treated with both BBP (i.g.) doses. Treatment with BBP (i.g.) at 250
      and 500 mg/kg doses for 7 days prior to DMBA administration resulted in a
      significant 37% decrease in mammary tumor incidence for both doses, compared to
      controls. The number of mammary adenocarcinomas per rat was significantly
      inhibited by 60 and 70% for rats exposed to BBP at the 250 and 500 mg/kg doses,
      respectively, compared to controls. Therefore, the present studies indicate that
      BBP acts as a blocking agent toward DMBA-induced rat mammary DNA adduct formation
      and mammary carcinogenesis. This effect partly may be due to increased metabolism
      of BBP in the liver. These results underscore the need to further examine the
      effect of BBP and other phthalates on the various stages of mammary
      carcinogenesis, as well as on the metabolism of mammary carcinogens.

PMID- 9276648
TI  - Dichloroacetic acid reduces Ha-ras codon 61 mutations in liver tumors from female
      B6C3F1 mice.
AB  - Dichloroacetic acid (DCA), a disinfection by-product of chlorination found in
      drinking water, is a hepatocarcinogenic in the B6C3F1 mouse. Previous studies
      have shown that DCA does not significantly alter the incidence of Ha-ras codon 61
      mutations in male mouse liver carcinomas from that observed in spontaneous tumors
      (approximately 50% have Ha-ras mutations) but it alters the proportions of
      mutations that occur in Ha-ras codon 61. Twenty-two tumors were produced in
      female B6C3F1 mice after treatment with 3.5 g DCA per liter of drinking water
      over a period of 104 weeks. To detect potential Ha-ras mutations in the liver
      tumor tissue of female B6C3F1 mice, genomic DNA was isolated from tumors that had
      been frozen. The polymerase chain reaction (PCR) and single-stranded
      conformational polymorphism (SSCP) was used to screen tumor DNA for mutations in
      Ha-ras exon 2. In DNA from liver tumors in female B6C3F1 mice induced by DCA
      treatment we found only one mutation in exon 2 among the 22 tumors analyzed
      (4.5%). Direct-sequencing of exon 2 revealed a CAA to CTA transversion in Ha-ras
      codon 61. The result of this study indicates that tumor formation in DCA-treated
      female B6C3F1 mice is, therefore, not associated with a mutationally activated Ha
      ras codon 61. This result differs from previous results obtained in male B6C3F1
      mice.

PMID- 9276649
TI  - Fasting during promotion, but not during initiation, enhances the growth of
      methylnitrosourea-induced mammary tumours.
AB  - The purpose of this work was to investigate the effect of fasting on the
      induction and growth of chemically-induced mammary carcinogenesis. Female Sprague
      Dawley rats were given methylnitrosourea (MNU) i.p. (50 mg/kg) at 50 days of age;
      a group of rats were exposed to 4 day fasting followed by 1 day of refeeding
      before the administration of the carcinogen, while another group was exposed to
      three cycles of 3 days fasting in 10 days, beginning 1 week after MNU injection.
      Fasting enhanced the development of mammary tumours only in rats fasted after
      carcinogen damage, while it did not affect the induction of tumours in rats
      fasted before MNU, if compared with full-fed controls. The enhanced growth of
      mammary tumours sustained by fasting during promotion was observed in the
      cervical-thoracic region. In addition, exposure to fasting made rats susceptible
      to the development of MNU-induced extra-mammary cancers. Different from the
      preventive effect of caloric restriction on tumor development, these data
      demonstrate that fasting affects the promotion phase of carcinogenesis by
      enhancing the growth of MNU-induced mammary tumours.

PMID- 9276650
TI  - First clinical judgment by primary care physicians distinguishes well between
      nonorganic and organic causes of abdominal or chest pain.
AB  - OBJECTIVE: To evaluate the accuracy of a preliminary diagnosis based solely on
      patient history and physical examination in medical outpatients with abdominal or
      chest pain. DESIGN: Prospective observational study. SETTING: General medical
      outpatient clinic in a university teaching hospital. PARTICIPANTS: One hundred
      ninety new, consecutive patients with a mean age of 44 years (SD = 14 years,
      range 30-58 years) with a main complaint of abdominal or chest pain. MEASUREMENTS
      AND MAIN RESULTS: The preliminary diagnosis, established on the basis of patient
      history and physical examination, was compared with a final diagnosis, obtained
      after workup at completion of the chart. A nonorganic cause was established in 66
      (59%) of 112 patients with abdominal pain and in 65 (83%) of 78 with chest pain.
      The preliminary diagnosis of "nonorganic" versus "organic" causes was correct in
      79% of patients with abdominal pain and in 88% of patients with chest pain. An
      "undoubted" preliminary diagnosis predicted a correct assessment in all patients
      with abdominal pain and in all but one patient with chest pain. Overall, only 4
      patients (3%) were initially incorrectly diagnosed as having a nonorganic cause
      of pain rather than an organic cause. In addition, final nonorganic diagnosis (n
      = 131) was compared with long-term follow-up by obtaining information from
      patients and, if necessary, from treating physicians. Follow-up information,
      obtained for 71% of these patients after a mean of 29 months (range 18-56 months)
      identified three other patients that had been misdiagnosed as having abdominal
      pain of nonorganic causes. Compared with follow-up, the diagnostic accuracy for
      nonorganic abdominal and chest pain at chart completion was 93% and 98%,
      respectively. CONCLUSIONS: A preliminary diagnosis of nonorganic versus organic
      abdominal or chest pain based on patient history and physical examination proved
      remarkably reliable. Accuracy was almost complete in patients with an "undoubted"
      preliminary diagnosis, suggesting that watchful waiting can be recommended in
      such cases.

PMID- 9276651
TI  - Medical information on the Internet: a study of an electronic bulletin board.
AB  - OBJECTIVE: To assess medical information provided in a medically oriented
      Internet discussion group, in terms of the professional status of the individuals
      providing information, the consistency of the information with standard medical
      practice, and the nature of the evidence cited in support of specific claims or
      recommendations. DESIGN: Standardized review of 1,658 consecutive messages on a
      particular online discussion group during a 5-month period. SETTING: An online
      discussion group for sufferers of painful hand and arm conditions. SUBJECTS: All
      participants in this discussion group during the study period. MEASUREMENTS AND
      MAIN RESULTS: Professional training of those offering medical information,
      consistency of the advice and recommendations offered with conventional medical
      practice, and nature of evidence cited in support of medical claims were
      determined. Of all messages, 55.9% (927) addressed a medical topic. Of these, 79%
      (732) provided medical information, of which 89.3% (654) were authored by persons
      without professional medical training, and 5.1% (37) were authored by trained
      health professionals. Approximately one third of the medical information provided
      was classified as unconventional. Personal experience was the basis of
      information provided in 61% of the nonprofessionals' messages and 13.5% of the
      professionals' messages, while no source was given as the basis of information
      provided in 29.8% of the nonprofessionals' messages and 67.6% of the
      professionals' messages. A published source was cited in 9.2% of the
      nonprofessionals' and 18.9% of the professionals' messages. CONCLUSIONS: These
      findings suggest that medical information available on Internet discussion groups
      may come from nonprofessionals and may be unconventional, based on limited
      evidence, and/or inappropriate.

PMID- 9276652
TI  - Is language a barrier to the use of preventive services?
AB  - OBJECTIVE: To isolate the effect of spoken language from financial barriers to
      care, we examined the relation of language to use of preventive services in a
      system with universal access. DESIGN: Cross-sectional survey. SETTING: Household
      population of women living in Ontario, Canada, in 1990. PARTICIPANTS: Subjects
      were 22,448 women completing the 1990 Ontario Health Survey, a population-based
      random sample of households. MEASUREMENTS AND MAIN RESULTS: We defined language
      as the language spoken in the home and assessed self-reported receipt of breast
      examination, mammogram and Pap testing. We used logistic regression to calculate
      odds ratios for each service adjusting for potential sources of confounding:
      socio-economic characteristics, contact with the health care system, and measures
      reflecting culture. Ten percent of the women spoke a non-English language at home
      (4% French, 6% other). After adjustment, compared with English speakers, French
      speaking women were significantly less likely to receive breast exams or
      mammography, and other language speakers were less likely to receive Pap testing.
      CONCLUSIONS: Women whose main spoken language was not English were less likely to
      receive important preventive services. Improving communication with patients with
      limited English may enhance participation in screening programs.

PMID- 9276653
TI  - Kidney transplant candidates' views of the transplant allocation system.
AB  - OBJECTIVES: The point system used to distribute scarce transplantable kidneys
      places great emphasis on antigen matching. This contributes to increased waiting
      times for African Americans, who have a disproportionate share of rare antigens.
      We conducted a pilot study to explore the understanding and attitudes of kidney
      transplant candidates toward the way the transplant allocation system trades off
      between antigen matching and waiting time. MEASUREMENTS AND MAIN RESULTS: We
      performed semi-structured interviews of a convenience sample of 33 patients
      awaiting transplants in Philadelphia and its surrounding suburbs. Patients had a
      number of misconceptions about the transplant allocation system. Many incorrectly
      thought, for example, that quality of life and financial status influence which
      patients on the waiting list receive available organs. Despite these and other
      misconceptions, the majority of patients thought the allocation system was fair.
      However, many African Americans thought the system was biased against them
      because of their race. After hearing about how the transplant system factors
      antigen matching and waiting time into organ allocation, the majority of subjects
      still felt the system was fair. After hearing that the emphasis on antigen
      matching causes African Americans to wait twice as long as whites, a larger
      number of subjects thought the system was unfair. Nevertheless, few thought the
      system should be changed. Even African American patients who felt the system was
      unfair still approved of the emphasis on antigen matching out of a desire to have
      a successful kidney transplant. CONCLUSIONS: We found that most of the
      interviewed patients awaiting kidney transplant thought the system should
      continue to emphasize antigen matching. Although attitudes toward the allocation
      system differed by race, with African American patients more suspicious of the
      system, the importance patients placed on antigen matching did not appear to
      differ by race.

PMID- 9276654
TI  - Lack of gender and racial differences in surgery and mortality in hospitalized
      Medicare beneficiaries with bleeding peptic ulcer.
AB  - OBJECTIVE: Determine the relation of race and gender to outcome from bleeding
      peptic ulcer. DESIGN: Retrospective cohort study. SETTING: All acute care
      hospitals in the United States. PATIENTS: A 100% sample of hospitalized Medicare
      beneficiaries older than 64 years (n = 82,868) with a primary discharge diagnosis
      of peptic ulcer with hemorrhage. MEASUREMENTS AND MAIN RESULTS: Surgical
      treatment was performed in 6.9% of patients, 30-day mortality was 8.5%, and
      average length of stay was 9.4 days. Surgery was somewhat more common in men than
      women (7.3% vs 6.5%, p < .001), and in whites than African Americans (6.9% vs
      6.3%, p < .001), but neither race nor gender was associated with surgery in
      multivariable analysis adjusting for potentially confounding factors. Mortality
      rates were similar in African Americans and whites (8.5%), and somewhat higher in
      men than women (10.7% vs 9.3%, p < .001). In multivariable analysis, there was no
      difference in mortality across gender and racial groups. Although unadjusted and
      adjusted lengths of stay were longer for African Americans and shorter for men,
      the differences were modest (i.e., 16% increase and 6% decrease in multivariable
      analysis, respectively, p < .0001). CONCLUSIONS: In this national sample, there
      is no significant gender or racial difference in therapy and outcome for patients
      with hemorrhagic peptic ulcer. The findings raise the possibility that studies
      that have shown race and gender differences in management of coronary artery
      disease and cancer may not be generalizable to other common diagnoses.

PMID- 9276655
TI  - Female "circumcision": African women confront American medicine.

PMID- 9276656
TI  - A clinician's view of statistics.

PMID- 9276657
TI  - The influence of knowledge and attitudes about breast cancer on mammography use
      among Latinas and Anglo women.
AB  - We conducted a telephone survey of randomly selected Latinas (n = 208) and Anglo
      women (n = 222) to determine predictors of mammography use. The cooperation rate
      was 78.5%. Relatively high proportions of Latinas (61%) and Anglo women (79%)
      reported mammography use within the past 2 years. A logistic regression analysis
      revealed that knowledge and attitudes did not independently predict use. On the
      other hand, having health insurance, being married, and being Latino were
      consistent independent predictors. We conclude that mammography use among Latinas
      and Anglo women is increasing. However, further gains in use must address
      difficult barriers such as lack of health insurance.

PMID- 9276658
TI  - Symptoms and science: the frontiers of primary care research.

PMID- 9276659
TI  - Online, health-related discussion groups: what we should know and do.

PMID- 9276660
TI  - A balanced approach to traditional female genital surgeries.

PMID- 9276661
TI  - The best test in the least time.

PMID- 9276662
TI  - Quantitative assessments from the clinical examination.

PMID- 9276663
TI  - Quality in HIV/AIDS care.

PMID- 9276664
TI  - Effect of subspecialty training and experience on agreement with HIV guidelines.

PMID- 9276665
TI  - Acyltransferases and transacylases involved in fatty acid remodeling of
      phospholipids and metabolism of bioactive lipids in mammalian cells.
AB  - Over 100 different phospholipid molecular species are known to be present in
      mammalian cells and tissues. Fatty acid remodeling systems for phospholipids
      including acyl-CoA: lysophospholipid acyltransferases, CoA-dependent and CoA
      independent transacylation systems and lysophospholipase/transacylase are
      involved in the biosynthesis of these molecular species. Acyl-CoA:1-acyl-2
      lysophospholipid acyltransferase prefers polyunsaturated fatty acyl-CoAs as acyl
      donors while acyl-CoA:2-acyl-1-lysophospholipid acyltransferase prefers saturated
      fatty acyl-CoAs. Therefore, the acyl-CoA:lysophospholipid acyltransferase system
      is involved in the synthesis of the phospholipid molecular species containing sn
      1 saturated and sn-2 unsaturated fatty acids. The CoA-dependent transacylation
      system catalyzes the transfer of fatty acids esterified in phospholipids to
      lysophospholipids in the presence of CoA without the generation of free fatty
      acids. The CoA-dependent transacylation reaction in rat liver exhibits strict
      fatty acid specificity, i.e., three types of fatty acids (20:4, 18:2, and 18:0)
      are transferred. On the other hand, the CoA-independent transacylase catalyzes
      the transfer of C20 and C22 polyunsaturated fatty acids from diacyl phospholipids
      to various lysophospholipids, in particular, ether-containing lysophospholipids,
      in the absence of any cofactors. The CoA-independent transacylase is assumed to
      be involved in the accumulation of polyunsaturated fatty acids in ether
      containing phospholipids and in the removal of deleterious ether-containing
      lysophospholipids. These acyltransferases and transacylases are involved in not
      only the remodeling of fatty acids but also the synthesis and degradation of some
      bioactive lipids and their precursors. In this review, the properties of these
      fatty acid remodeling systems and their possible roles in the biosynthesis of
      bioactive lipids are described.

PMID- 9276666
TI  - Molecular cloning, genomic organization, promoter activity, and tissue-specific
      expression of the mouse ryudocan gene.
AB  - Ryudocan, a ubiquitous heparan sulfate proteoglycan, is a member of the syndecan
      family of cell surface proteoglycans. The full-length cDNA encoding the murine
      ryudocan core protein has now been cloned and sequenced. The deduced primary
      structure of mouse ryudocan, including the three glycosaminoglycan attachment
      sites in the extracellular domain as well as the transmembrane and cytoplasmic
      regions, is highly similar to those of the rat, human, and chicken proteins.
      Northern analysis detected a 2.7-kb transcript in all mouse tissues examined,
      with the highest concentrations apparent in liver, kidney, and lung. The mouse
      ryudocan gene was shown to span approximately 19.7 kb of genomic DNA and to
      contain five exons, with an intron-exon organization identical to that of the
      human gene. The promoter region of the mouse gene contains various cis-acting
      elements, including a TATA-like box and a GC box as well as potential binding
      sites for the transcription factors NF-IL6, MyoD, GATA, C/EBP, AP-2, NF-kappaB,
      AP-1, and Sp1. Transient transfection experiments with a construct containing the
      690 bp upstream of the transcription start site fused to a luciferase reporter
      gene showed functional promoter activity. Deletion analysis suggested that the
      proximal promoter region including the TATA-like box, the GC box, and other Sp1
      binding sites was required for full transcriptional activity. These findings will
      be useful for the study of ryudocan gene regulation and the generation of mice
      with targeted disruption of the gene.

PMID- 9276667
TI  - Influence of mutations of the N-cap residue, Gly4, on stability and structure of
      hen lysozyme.
AB  - Hen lysozyme, with three alpha-helices (A, B, and C), is a c-type lysozyme. In
      these lysozymes, Ser24 and Asp88 located at the N-cap position in the B- and C
      helix, respectively, are mostly conserved, but residue 4 at the N-cap position in
      A-helix is variable. To investigate the effect of mutation at position 4 on the
      stability of hen lysozyme, we prepared five mutant lysozymes and examined their
      stabilities and structures. Gly4Pro lysozyme (G4P), in which Gly4 was replaced by
      Pro, was less stable by 8.8 kJ/mol than the wild-type lysozyme, possibly because
      the side chain at position 7 is shifted away from the A-helix. The other mutant
      lysozymes were of almost equal stability to the wild-type lysozyme, although the
      hydrogen bonds of the amide groups at positions N1-N3 in the A-helix were absent
      or altered. These results indicated that various mutations at the N-cap position
      in the A-helix would be allowed as long as the negative charge of Glu7 at the N
      terminus stabilized the A-helix.

PMID- 9276668
TI  - Extremely thermostable phosphoenolpyruvate carboxylase from an extreme
      thermophile, Rhodothermus obamensis.
AB  - Phosphoenolpyruvate carboxylase (PEPC) was purified from an extremely
      thermophilic bacterium, Rhodothermus obamensis, growing optimally at 80 degrees
      C, which had recently been isolated from a shallow marine hydrothermal vent in
      Japan. The native enzyme was a homotetramer of 400 kDa in molecular mass, as
      estimated by gel filtration chromatography, and the subunit exhibited an apparent
      molecular mass of 100 kDa on sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. The optimum temperature for enzyme activity was 75 degrees C.
      The enzyme exhibited an absolute requirement for divalent cations and a pH
      optimum of 8.0. The enzyme was extremely thermostable and there was no loss of
      enzyme activity on incubation for 2 h at 85 degrees C. The enzyme exhibited a
      positive allosteric property with acetyl-CoA and fructose 1,6-bisphosphate, and a
      negative one with L-aspartate and L-malate. These effectors affected not only the
      thermophilicity but also the thermostability of the enzyme, and the substrate, co
      factors, and salts increased the thermostability as well. The extrinsic
      thermostabilization might be a possible mechanism for adaptation of the enzyme to
      high temperature.

PMID- 9276669
TI  - Structure and expression of the dnaKJ operon of Buchnera, an intracellular
      symbiotic bacteria of aphid.
AB  - Buchnera sp., an intracellular symbiont of the pea aphid (Acyrthosiphon pisum
      Harris), is a close phylogenetical relative of Escherichia coli, and synthesizes
      a large amount of symbionin, a GroEL homolog. The other heat shock protein
      homologs, which are not expressed as much as symbionin, have not been studied
      yet. In this study, we cloned the dnaK and dnaJ genes of Buchnera, and revealed
      that its DnaK and DnaJ are structurally very similar to those of E. coli. Amino
      acid residues and motifs proposed so far to be essential for the function of the
      E. coli DnaK and DnaJ were completely conserved in the Buchnera counterparts.
      However, Buchnera dnaKJ operon could not fully complement mutations of either
      dnaK or dnaJ of E. coli. This is probably because of a difference in net charge
      of DnaK and DnaJ between Buchnera and E. coli, and a unique structure of Buchnera
      DnaJ that prevents heterologous components from operating in concert. Buchnera
      dnaK and dnaJ formed an operon whose transcription is governed by a promoter
      structurally homologous to heat shock promoters of E. coli, although the cellular
      amount of dnaKJ mRNA was not affected by heat shock. Two inverted repeats
      flanking both sides of E. coli dnaJ were also found in the gene of Buchnera at
      the corresponding positions, suggesting that expression ratio of DnaK to DnaJ is
      regulated in a similar manner in the two organisms.

PMID- 9276670
TI  - Collagen degradation induced by the combination of IL-1alpha and plasminogen in
      rabbit articular cartilage explant culture.
AB  - To investigate the effect of plasminogen on cartilage catabolism, we assessed
      collagen degradation in rabbit articular cartilage explants treated with or
      without plasminogen and interleukin-1alpha (IL-1alpha). The combination of IL-1
      alpha and plasminogen induced rapid collagen degradation, amounting to more than
      60% of the total collagen by day 7, while neither IL-1alpha nor plasminogen alone
      had any effect. To examine the mechanism of collagen degradation induced by IL
      1alpha and plasminogen, the matrix metalloproteinases (MMPs) in the culture
      supernatants were examined by ELISA, Western blotting and gelatin zymography. We
      found that the treatment with IL-1alpha induced MMP-1, MMP-3, and MMP-9. In
      addition, plasminogen converted the pro form of MMPs into the active form. Both a
      tissue inhibitor of metalloproteinases-1 (TIMP-1) and a synthetic hydroxamate MMP
      inhibitor prevented this collagen release. These results suggest that plasminogen
      causes collagen degradation via activation of MMPs induced by IL-1alpha.

PMID- 9276671
TI  - Enzyme flexibility: a new concept in recognition of hydrophobic substrates.
AB  - The mechanism of recognition of hydrophobic substrates was investigated using
      Escherichia coli aspartate aminotransferase (AspAT), E. coli aromatic amino acid
      aminotransferase (AroAT), and their chimeric enzyme (DY18). Surprisingly, broad
      substrate specificity was observed in the reaction of aminotransferases with
      hydrophobic substrates. The catalytic efficiency increased with an increase in
      the side chain length of straight or branched-terminal aliphatic substrates. The
      straight-chain substrates catalysed with maximal efficiency were the 7-carbon
      substrate in the case of AspAT and the 8-carbon substrate for AroAT and DY18.
      Consecutive addition of single methylene groups to the substrate had a constant
      effect on the stabilization energy of the transition state relative to the
      unbound state. The dependency of binding energy on each methylene group is
      usually interpreted as indicating hydrophobicity of the active site. However, we
      observed that AroAT and DY18 had different dependencies although both enzymes
      have the same residues in the substrate-binding pocket. For substrates with more
      than 7 carbons, the aminotransferases did not strictly distinguish between
      substrates with straight and branched side chains. These results suggest that the
      recognition of manifold hydrophobic substrates of different shapes might require
      not only the hydrophobicity of the active site but also enzyme flexibility.

PMID- 9276672
TI  - H+ secretion induced by hypertonic stress in the cellular slime mold
      Dictyostelium discoideum.
AB  - We found that Dictyostelium amebas shrank about 50% in 10 min after a change in
      extracellular osmolarity from 70 mosM to 170-370 mosM. Cells shrunk by the
      addition of 0.1 M mannitol showed a partial recovery of cell volume in 2 h when
      the culture medium contained salts. A full recovery of cell volume was observed
      when 0.1 or 0.2 osM NaCl or KCl was added instead of mannitol. No recovery of
      cell volume was observed after the addition of 0.1 M mannitol or glycine when the
      extracellular medium did not contain any salt. An elevation in extracellular pH
      of starved Dictyostelium cells, which is probably due to ammonia production, was
      suppressed by hypertonic stress. This hypertonic stress-induced suppression of
      the elevation in extracellular pH was observed only when the extracellular medium
      contained salt. We also found that cells with artificially elevated intracellular
      pH withstood hypertonic stress much better than control cells. These results
      suggest that Dictyostelium cells under hypertonic conditions secrete protons and
      take up charged extracellular osmolytes in exchange. The uptake of charged
      osmolytes induces the elevation of intracellular osmotic strength and the
      recovery of cell volume. The elevation of intracellular pH, which is presumably
      induced by the proton secretion, plays a role in protecting cells from lysis.

PMID- 9276673
TI  - Molecular cloning and sequencing of cDNAs encoding three heavy-chain precursors
      of the inter-alpha-trypsin inhibitor in Syrian hamster: implications for the
      evolution of the inter-alpha-trypsin inhibitor heavy chain family.
AB  - Complementary DNAs encoding precursors of the three heavy chains (HC1, HC2, HC3)
      of the inter-alpha-trypsin inhibitor in Syrian hamster liver were sequenced. The
      deduced amino acid sequence of the HC1 precursor was 87, 82, and 79% identical
      with those of the HC1 precursors from mouse, man and pig, respectively. The HC2
      and HC3 precursors showed similar degrees of sequence identity with the
      corresponding human and mouse HC precursors. When the hamster HC1 precursor was
      compared with its own HC2 and HC3 precursors, however, even the most highly
      conserved segment consisting of 565 amino acid residues, i.e., about 2/3 of the
      whole molecule, showed only about 35 and 65% sequence identity, respectively.
      Essentially the same results were obtained on the intra-species comparisons of
      three subfamilies in man and mouse. Thus, the interspecies conservation of a
      given HC subfamily is much greater than the similarity between the three
      different HC subfamilies within a given species. These results suggest that (i)
      higher vertebrates possess three HC genes which have been evolving independently
      of each other under purifying selection; (ii) the diversification of the three HC
      subfamilies, for which the middle regions of the molecules were mainly
      responsible, occurred before eutherian radiation; and (iii) each HC subfamily may
      have unique function(s), although at present virtually nothing is known about the
      functional differences between the three HC subfamilies.

PMID- 9276674
TI  - Refolding of urea-denatured ovalbumin that comprises non-native disulfide
      isomers.
AB  - Ovalbumin, which contains one cystine disulfide (Cys73-Cys120) and four cysteine
      sulfhydryls (Cys11, Cys30, Cys367, and Cys382) in the native state, undergoes
      intrachain sulfhydryl-disulfide exchanges at high concentrations of urea,
      generating many non-native disulfide isomers [E. Tatsumi, N. Takahashi, and M.
      Hirose (1994) J. Biol. Chem. 269, 28062-28067]. The refolding of ovalbumin from
      the urea-denatured state was investigated. When the denatured protein was diluted
      20-fold with a refolding buffer (pH 8.2), an initial burst intermediate I(N) was
      produced within the 20 ms instrumental dead time; I(N) showed about 60% of the
      native CD ellipticity at 222 nm. The intrinsic tryptophan fluorescence of I(N)
      showed the same peak (338 nm), but with decreased intensity (57%), as compared to
      the native protein. After the rapid formation of I(N), most of the ovalbumin
      molecules correctly refolded into the native state with slow biphasic kinetics,
      as evaluated by far-UV CD, tryptophan fluorescence, and trypsin-resistance
      analyses. Furthermore, a peptide-mapping analysis revealed that
      sulfhydryl/disulfide exchange reactions occurred during the refolding, thereby
      increasing the formation of the native disulfide. The integrity of overall
      refolding was confirmed by a differential scanning calorimetry analysis. These
      data were consistent with the view that most, if not all, of the mispaired
      disulfide isomers in the urea-denatured ovalbumin can correctly refold into the
      native state via intrachain disulfide rearrangements.

PMID- 9276675
TI  - The beta3-adrenergic agonist BRL37344 increases glucose transport into L6
      myocytes through a mechanism different from that of insulin.
AB  - In the present study, we examined the effects of BRL37344, a selective beta3
      adrenergic agonist, on glucose transport into L6 myocytes and the results were
      compared with the effects of insulin. Insulin increased 2-deoxyglucose (2-DG)
      uptake in a dose-dependent manner, with maximal stimulation at 10(-7)M. BRL37344
      ranging from 10(-7) to 10(-5)M also enhanced 2-DG uptake in the absence of
      insulin. The effects of insulin and BRL37344 were completely additive, suggesting
      that these two agents enhance glucose uptake by L6 myocytes through different
      mechanisms. In fact, BRL37344 apparently did not increase tyrosine
      phosphorylation of cellular proteins in L6 myocytes, whereas insulin stimulated
      tyrosine phosphorylation of 180-190 and 95 kDa proteins. Furthermore, BRL37344
      induced increase in glucose transport was not blocked by wortmannin, an inhibitor
      of phosphatidylinositol 3-kinase, whereas the insulin-induced effect was
      completely abolished. When L6 myocytes were incubated with insulin, the content
      of GLUT4 in the plasma membrane was increased. However, BRL37344 did not affect
      the GLUT4 content in the plasma membrane. BRL37344 did not increase the Vmax
      value for glucose uptake but decreased the Km value, although insulin increased
      the Vmax value. These results suggest that BRL37344 enhances glucose transport
      into L6 myocytes through a signaling pathway different from that of insulin and
      that the mechanism does not involve the translocation of GLUT4, but may be due to
      an increase in the intrinsic activity of GLUT present in the plasma membrane.

PMID- 9276676
TI  - Immortalized gastric epithelial cell line GSM06 synthesizes hyaluronan under the
      influence of simian virus 40 large T-antigen expression.
AB  - GSM06 is a cell line established from the stomach of transgenic mouse harboring a
      temperature-sensitive simian virus 40 (SV40) large T-antigen gene. 3H-labeled
      macromolecules produced by the cells incubated with [3H] glucosamine were
      characterized to examine whether or not GSM06 cells synthesize mucin (mucus
      glycoprotein). The GSM06 cells grew until a confluent monolayer formed at 33
      degrees C (the permissive temperature for SV40 large T-antigen expression), and
      the 3H-labeled macromolecules appeared in both cell extract and medium during
      culture for at least 1 week. Unexpectedly, almost all 3H-labeled macromolecules,
      which were excluded from a column of Sepharose CL-4B, were identified as
      hyaluronan by analyses using Sepharose CL-2B chromatography, cesium
      trifluoroacetate equilibrium centrifugation, treatment with dithiothreitol, and
      trypsin, hyaluronidase, and chondroitinase ABC digestion. At a nonpermissive
      temperature (39 degrees C), GSM06 cells grew only slightly, but produced much
      more hyaluronan than at 33 degrees C. The results indicate that GSM06 cells
      produce not mucin, but hyaluronan, and that the expression of large T-antigen may
      influence hyaluronan synthesis in GSM06 cells.

PMID- 9276677
TI  - Bound Tris confounds the identification of binding site residues in a paraquat
      single chain antibody.
AB  - We produced an anti-paraquat single chain antibody (scFv) to investigate its
      potential use in immunotherapy for paraquat poisoning. However, this scFv was
      expressed in an insoluble form and only displayed moderate binding affinity. An
      earlier examination of the pH dependence of antigen binding by the parent
      paraquat-specific mAb (7D7-3) suggested that the electrostatic effects of a
      tyrosine residue were important. The aims of the current study were to obtain
      expression of a soluble scFv (D10) and to increase its binding affinity. The
      former was achieved by expression in a phagemid vector. Site-directed mutagenesis
      of tyrosine residues in CDR H3 did not result in improved affinity for paraquat,
      suggesting that the original pH dependence required re-examination. Nuclear
      magnetic resonance studies of 7D7-3 Fab revealed that the original observation of
      the pH-dependent paraquat binding with a mid-point of approximately pH 8.9 was
      due to tightly bound Tris. It appears that as Tris is titrated to a neutral
      species the energetically unfavourable juxtaposition of its positive charge with
      that of paraquat is reduced. These findings have broad implications in the
      interpretation of the pH or salt dependence of any antibody-antigen interaction
      which should be made cautiously and with regard to the possible interference of
      buffer components introduced during the preparation of the antibody.

PMID- 9276678
TI  - Glycosylation of human bone collagen I in relation to lysylhydroxylation and
      fibril diameter.
AB  - Posttranslational modifications (lysylhydroxylation, glycosylation, and crosslink
      formation) of collagen I and the trabecular bone volume (TBV) as well as the
      supramolecular organization of human vertebrae were studied by analyzing
      vertebral bones of 55 individuals (22-93 years of age). The degree of
      lysylhydroxylation of both a-chains of collagen I showed a significant inverse
      correlation with the TBV, while only a weak correlation between
      lysylhydroxylation of alpha2(I) and the age of the donor was observed. The degree
      of glycosylation of collagen I was significantly correlated with both the level
      of lysylhydroxylation and the degree of osteopenia. Electron microscopic
      evaluation did not show any relationship between the level of collagen
      glycosylation and the diameter of in vivo formed fibrils or in vitro formed
      fibrillar aggregates. In our study the molar ratio of the mature collagen
      crosslinks, pyridinoline and deoxypyridinoline, showed a slight tendency to be
      higher, in particular in the samples with a high level of lysylhydroxylation.
      This ratio was recently found to be significantly increased in avian osteoporotic
      bone. Our data suggest that the increased level of lysylhydroxylation in human
      osteopenia is related to the glycosylation of collagen I, while it seems to have
      little impact on the formation of the mature, non-reducible collagen crosslinks
      investigated. Based on our observations it appears unlikely that the different
      diameters of collagen fibrils contribute greatly to the reduced biomechanical
      stability reported for overhydroxylated, osteopenic bone tissue.

PMID- 9276679
TI  - Ligand-binding enhances the affinity of dimerization of the extracellular domain
      of the epidermal growth factor receptor.
AB  - We studied the dimerization of the recombinant soluble extracellular domain of
      the epidermal growth factor receptor (sEGFR) in response to EGF-binding using
      multi-angle laser light scattering with size exclusion chromatography (SEC
      MALLS). In the absence of EGF, sEGFR behaved as a monomer. However, upon EGF
      binding, sEGFR formed a dimer with the stoichiometry of two EGF molecules bound
      to two sEGFR molecules [(EGF)2-(sEGFR)2]. We analyzed the chemical equilibrium of
      the dimer formation by SEC-MALLS using a dissociation constant of 0.25 microM for
      the binding of EGF to sEGFR. The calculated dissociation constant for EGF-induced
      sEGFR dimerization was found to be 2.4 +/- 0.9 microM. These experiments
      demonstrated that EGF induces receptor dimerization and that two EGF molecules
      are bound to an EGF-receptor dimer.

PMID- 9276680
TI  - Characterization of a human placental fructose-6-phosphate, 2-kinase/fructose-2,6
      bisphosphatase.
AB  - A full-length cDNA, which encodes a human placental fructose-6-phosphate,2
      kinase/ fructose-2,6-bisphosphatase, was constructed and expressed in Escherichia
      coli. The expressed protein, purified to homogeneity, showed a molecular weight
      of 58,000 by gel electrophoresis under denaturing conditions, compared to the
      deduced molecular weight of 59,410. The N-terminal sequence of 15 amino acids
      coincided with that of the deduced sequence. The active enzyme was a dimer as
      judged by molecular sieve filtration. The expressed enzyme was bifunctional with
      Vmax values of 142 and 0.2 milliunits/mg for the kinase and phosphatase
      activities, respectively. The phosphatase activity was extremely low, because one
      phosphatase active site residue was mutated, and consequently the
      kinase/phosphatase ratio was the highest among the known isozymes. Furthermore,
      the enzyme was phosphorylated by cAMP-dependent protein kinase, protein kinase C
      and also by [2-32P]fructose-2,6-bisphosphate. Phosphorylation by cAMP-dependent
      protein kinase and protein kinase C increased the maximal Fru-6-P,2-kinase
      activities by 1.8- and 1.1-fold, respectively. These results suggested that
      placental fructose-6-phosphate,2-kinase/ fructose-2,6-bisphosphatase is important
      in maintaining and regulating a relatively high rate of glycolysis in placenta.

PMID- 9276681
TI  - A survey of genes expressed in mouse embryonal carcinoma F9 cells:
      characterization of expressed sequence tags matching no known genes.
AB  - We prepared 2,132 expressed sequence tags (ESTs) from undifferentiated mouse
      embryonal carcinoma F9 cells and found that 1,416 match known gene and/or protein
      sequences [Nishiguchi et al. (1996) J. Biochem. 119, 749-767]. To obtain
      information on the functions of the remaining 716 unidentified ESTs and to
      develop a system for characterizing ESTs matching no known genes, we analyzed
      their sequences by (i) repeated database searches, using the BLASTN, BLASTX,
      TBLASTX, and FASTA programs, (ii) using computer programs developed or modified
      for this work, such as the WFASTA, ORFTRNS, and MFASTA programs, together with
      the DBPROSITE and GRAIL programs, and (iii) examining the expression patterns of
      the corresponding mRNAs in F9 cells and several organs of adult mice, using the
      digoxigenin-labeled dot-blot method. We found that 216 of the 716 ESTs match
      known gene and/or protein sequences, and 307 show significant similarities to
      these sequences, with a Poisson p-value < 0.01. The strategy and usefulness of
      such analysis for characterizing unidentified ESTs are discussed.

PMID- 9276682
TI  - Structures of the sugar chains of recombinant macrophage colony-stimulating
      factor produced in Chinese hamster ovary cells.
AB  - The structures of the N- and O-linked sugar chains of recombinant human
      macrophage colony-stimulating factor (rhM-CSF) from Chinese hamster ovary (CHO)
      cells were studied. rhM-CSF is a homodimeric glycoprotein. Sugar composition
      analysis revealed that rhM-CSF contained 4.1 mol N-acetylgalactosamine, 10.3 mol
      N-acetylglucosamine, 5.0 mol mannose, 10.0 mol galactose, 1.4 mol fucose, and
      11.8 mol sialic acid per mol of the monomer. The N- and O-linked sugar chains
      liberated by hydrazinolysis were N-acetylated, and the reducing-end sugar
      residues were tagged with 2-aminopyridine. The pyridylamino (PA-) sugar chains
      thus obtained were purified by HPLC. The structures of the PA-sugar chains were
      analyzed by a combination of reversed-phase and size-fractionation HPLC, and
      exoglycosidase digestions, from which the structures of the rhM-CSF sugar chains
      were estimated to be as follows: monosialo biantennary sugar chain (9 mol%),
      monosialo fucosylbiantennary sugar chain (10 mol%), disialo biantennary sugar
      chain (30 mol%), disialo fucosylbiantennary sugar chain (28 mol%), disialo
      triantennary sugar chain (7 mol%), trisialo triantennary sugar chain (11 mol%),
      and trisialo fucosyltriantennary sugar chain (5 mol%) for the N-linked sugar
      chains, and asialo (27 mol%), monosialo (51 mol%), and disialo (22 mol%) Galbeta1
      3GalNAc for the O-linked sugar chains. Sialic acid residues were linked to the N
      linked sugar chains through an alpha2-3 linkage.

PMID- 9276683
TI  - Structure and expression of the human SM22alpha gene, assignment of the gene to
      chromosome 11, and repression of the promoter activity by cytosine DNA
      methylation.
AB  - To investigate the molecular mechanisms that control expression of smooth muscle
      cell (SMC) differentiation genes, we have isolated the human SM22a gene, which is
      composed of five exons and four introns, spanning an approximately 6-kilobase
      (kb) genomic DNA at chromosome region 11q23.2. Expression of the SM22a messenger
      RNA was detected in serum-stimulated cell cultures including SMC,
      undifferentiated skeletal muscle-lineage cells, and fibroblasts, and it was down
      regulated in SMC of balloon-injured atheromatous human vessels. A major
      transcription start site of the SM22alpha gene is located at 75 base-pairs (bp)
      upstream of the ATG start codon. Analysis of the 2.6 kb 5'-upstream sequence
      demonstrated that two CArG/SRF-boxes and two GC-box/Sp1-binding sites were
      present at bp -147 and -274, and at bp -233 and -1635, respectively. The
      nucleotide sequences of the two CArG/SRF-boxes and the proximal GC-box/Sp1
      binding site are 100% conserved with those of the murine SM22alpha genes [Solway,
      J., Seltzer, J., Samaha, F.F., Kim, S., Alger, L.E., Niu, Q., Morriesey, E.E.,
      Ip, H.S., and Parmacek, M.S. (1995) J. Biol. Chem. 270, 13460-13469; Kemp, P.R.,
      Osbourn, J.K., Grainger, D.J., and Metcalf, C. (1995) Biochem. J. 310, 1037
      1043]. Cell transfection assays using a luciferase reporter gene construct
      containing the 455-bp 5'-flanking region (positions -26 to -480) showed that
      methylation of the CpG dinucleotides within this segment reduces its
      transcriptional activity. The results imply a novel mechanism for transcriptional
      control of the SMC differentiation-specific gene promoter.

PMID- 9276684
TI  - A new peptide conjugate as a highly specific substrate for MAP kinase.
AB  - A synthetic peptide (APRTPGGRC) cross-linked to poly-L-lysine through a carboxy
      terminal cysteinyl residue was found to be a highly specific substrate for
      mitogen-activated protein (MAP) kinases. This peptide conjugate exhibited a much
      lower Km value (74 microM) than the free peptide substrate (APRTPGGRR, Km > 1 mM)
      previously used as a specific substrate for MAP kinases. Unlike myelin basic
      protein, which has been often used as a substrate for MAP kinases, this conjugate
      did not serve as substrate for cAMP-dependent protein kinase, protein kinase C,
      or multifunctional calmodulin-dependent protein kinases. Using the peptide
      conjugate as a substrate, MAP kinase activities in crude cell extracts were
      directly determined by in vitro assay and specifically detected by in-gel assay.

PMID- 9276685
TI  - Induction of calcium release from isolated sarcoplasmic reticulum by
      triphenyltin.
AB  - A direct peripheral myopathy has been found in organotin intoxication and
      suggested to be a significant factor in the development of muscle weakness
      following exposure. In this study, by using the isolated sarcoplasmic reticulum
      membrane vesicles, we have shown that triphenyltin dose-dependently induced Ca2+
      release from the actively and passively loaded sarcoplasmic reticulum vesicles.
      Triphenyltin induced Ca2+ release in ruthenium red-sensitive and insensitive ways
      with EC50 values of 75 and 270 microM, respectively. The Ca2+-ATPase activity and
      Ca2+ uptake of sarcoplasmic reticulum were also inhibited by triphenyltin.
      Triphenyltin exerted dual effects on the apparent [3H]ryanodine binding.
      Triphenyltin (0.5-10 microM) dose-dependently potentiated the [3H]ryanodine
      binding; however, the [3H]ryanodine binding decreased as the concentration of
      triphenyltin increased. The dissociation of bound [3H]ryanodine was facilitated
      by triphenyltin. The present study suggested that the internal Ca2+ store of
      skeletal muscle could be depleted by triphenyltin through the inhibition of the
      Ca2+ uptake and the induction of Ca2+ release by acting on the Ca2+-ATPase and
      Ca2+ release channel, also known as the ryanodine receptor, of sarcoplasmic
      reticulum, respectively. These results could partly explain the development of
      muscle weakness in organotin intoxication; however, their relevance to the
      development of peripheral myopathy requires further examination.

PMID- 9276686
TI  - Tissue and subcellular distributions, and characterization of rat brain protein
      phosphatase 2A containing a 72-kDa delta/B" subunit.
AB  - A 74-kDa delta/B" subunit was isolated by heparin-Sepharose column chromatography
      from human erythrocyte protein phosphatase 2A (PP2A) consisting of a 34-kDa
      catalytic subunit (alpha/C) and 63- and 74-kDa regulatory subunits (beta/A and
      delta/B") in a ratio of 1:1:1. The purified delta/B" was used as an immunogen in
      mice, to prepare specific antisera against delta/B". Immunoblot analyses with the
      antisera detected an immunoreactive 72-kDa protein in the cytosol from various
      rat tissues including erythrocytes, brain, lung, testis, adrenal gland, heart,
      spleen, kidney, and liver. The 72-kDa protein was highly abundant in brain and
      was distributed evenly in cerebral cortex, cerebellum, and brain stem. The 72-kDa
      protein was also detected in mitochondria and microsome fractions. An
      immunoreactive 68-kDa protein was detected mainly in nuclear and microsome
      fractions. The 72-kDa protein from rat brain cytosol copurified with
      phosphorylated H2B histone phosphatase activity during successive
      chromatographies on DEAE-Toyopearl, AH-Sepharose, Sephadex G-150, H1 histone
      Toyopearl, TSK DEAE-5PW, protamine-Toyopearl, and TSK G3000SW columns. The
      purified enzyme migrated as a single protein band on nondenaturing PAGE and as
      three protein bands of 34, 63, and 72 kDa in a ratio of 1:1:1 on SDS-PAGE. The
      molecular weight of the enzyme was estimated to be 170,000 from the s20,W value
      of 7.2 +/- 0.3 S and the Stokes radius of 5.5 +/- 0.1 nm. The rat brain enzyme
      was classified as PP2A, based on the following properties; (1) an IC50 for
      okadaic acid of 10(-9) M; (2) its preferential dephosphorylation of the a subunit
      of phosphorylase kinase; (3) its insensitivity to protein inhibitor 2; and (4)
      its heterotrimeric subunit structure. The Km value and the molecular activity of
      the enzyme for phosphorylated H2B histone were 72.3 +/- 0.3 microM and 192 +/- 2
      mol Pi released/min/mol enzyme, respectively, and were comparable to those of
      human erythrocyte PP2A (alpha1 beta1 delta1/ CAB"). The 72-kDa subunit in the
      purified rat brain PP2A was phosphorylated in vitro by cAMP-dependent protein
      kinase.

PMID- 9276687
TI  - Effect of aromatic nitroso-compounds on superoxide-generating activity in
      neutrophils.
AB  - Aromatic nitroso-compounds such as nitrosobenzene inhibited the respiratory burst
      of intact neutrophils induced by various stimulants, including phorbol 12
      myristate 13-acetate and a chemotactic peptide. The compounds also inhibited
      NADPH-dependent oxygen consumption by cell-free preparations of neutrophils. This
      indicates that nitroso-compounds act directly on the NADPH-oxidase system. The
      inhibitory effects induced by several nitroso-compounds, 2-nitrosotoluene,
      nitrosobenzene, 4-nitrosophenol, and 1-nitrosopyrrolidine, were examined and
      their inhibition constants, the concentrations causing 50% reduction of oxygen
      consumption, were found to be 0.043, 0.173, 0.672, and 32.1 mM, respectively.
      These values correlated well with the hydrophobicity of the compounds: a more
      hydrophobic compound was a more potent inhibitor against NADPH oxidase,
      suggesting that the oxidase has a hydrophobic site(s) for interaction with the
      inhibitors.

PMID- 9276688
TI  - Cleavage site mapping and substrate-specificity of Leishmaniavirus 2-1 capsid
      endoribonuclease activity.
AB  - The Leishmaniavirus capsid protein possesses an RNA endoribonuclease activity
      that cleaves viral positive-sense RNA at a specific, single site within the 5'
      untranslated region. The site of cleavage in LRV1-4 RNA was previously mapped to
      nucleotide 320 of the LRV1-4 genome. Here we show that an LRV2-1-derived
      substrate RNA transcript is also cleaved at a single site in an in vitro cleavage
      assay with LRV2-1 virions. Precise RNA cleavage site mapping in this divergent
      Old World virus, LRV2-1, confirms that cleavage is occurring within a region of
      homology to the LRV1 isolates. Substrate RNA transcripts possessing viral
      sequences from LRV1-4 or LRV2-1 genomes were assayed for susceptibility to
      cleavage by the cognate and noncognate capsid endoribonucleases to determine the
      level of substrate specificity.

PMID- 9276689
TI  - Crystallization and preliminary X-ray diffraction studies of expressed
      Pseudomonas putida catechol 2,3-dioxygenase.
AB  - Crystals of recombinant Pseudomonas putida catechol 2,3-dioxygenase, metapyrocate
      chase, composed of four identical subunits, each with a molecular mass of 35 kDa
      and one nonheme ferrous iron, have been grown by the vapor diffusion method using
      sodium citrate as the precipitant. Repeated macroseeding and the addition of
      ethanol to protein solutions were together effective for obtaining crystals
      suitable for further crystallographic characterization. The crystals belong to
      the tetragonal space group P4(2)2(1)2 with unit-cell dimensions of a = b = 266 A,
      c = 60 A. They diffracted beyond 2.5 A resolution with synchrotron radiation.
      Assuming that one tetramer (alpha-Fe2+)4 is contained in an asymmetric unit, the
      crystal volume per unit molecular mass, Vm, is calculated to be 3.8 A3/Da, which
      corresponds to the solvent content of 67.6%.

PMID- 9276690
TI  - Unexpectedly general replaceability of ATP in ATP-requiring enzymes.
AB  - ATP-dependent enzymes were investigated as to the stringency of their ATP
      requirement. For all the enzymes examined except firefly luciferase (including
      hexokinase, polynucleotide kinase, T4 DNA ligase, and T4 RNA ligase) ATP could be
      replaced with dATP, contradicting previous data. Considering the replaceable
      nucleotides, not only kinases (low stringency as to ATP-requirement) but also
      other enzymes (moderate stringency) were typed as phosphate-directed ATP
      recognition. Through this study, an exact view of ATP-requiring enzymes which
      have a profound influence on the concentration in a cell of ATP, a metabolic and
      regulative key substance, was obtained, and a technically useful, fluorescent ATP
      substitute (2AP-TP) was introduced.

PMID- 9276691
TI  - Alternative translation initiation generates acyl-CoA synthetase 3 isoforms with
      heterogeneous amino termini.
AB  - ACS3 is a recently identified acyl-CoA synthetase (ACS) isozyme that
      preferentially utilizes laurate, myristate, arachidonate, and eicosapentaenoate
      among saturated and unsaturated long chain fatty acids. The ACS3 purified from
      COS cells transfected with the ACS3 cDNA was separated by SDS-PAGE into two major
      forms of 79 and 80 kDa. We report here that alternative translation initiation
      from ACS3 mRNA gives rise to these two isoforms of ACS3. In vitro mutagenesis of
      the ACS3 cDNA revealed that the translation of the 80-kDa and 79-kDa isoforms
      started from the first and second in-frame AUGs, respectively. The two isoforms
      of ACS3 expressed in COS cells exhibited similar levels of ACS activities toward
      palmitate and myristate. Immunocytochemistry of intact COS cells transfected with
      various ACS3 expression vectors suggested that the two forms are localized in the
      extranuclear compartment, where they exhibit a reticular pattern. In rat
      cerebrum, the 80-kDa isoform of ACS3 was detected mainly in the microsomal
      fraction. Only a trace amount of the 79-kDa isoform was detected in rat cerebrum,
      whereas both forms were detected in rat glioma cell line KEG1 cells.

PMID- 9276692
TI  - Effects of amino acid side-chain volume on chain packing in genetically
      engineered periodic polypeptides.
AB  - The fidelity of bacterial protein synthesis allows the production of
      architecturally well-defined polymeric materials through precise control of chain
      length, sequence, stereochemistry, and interchain interactions. In the present
      paper, we examine the relation between amino acid residue volume and crystalline
      unit cell dimensions, in a set of periodic protein polymers of repeating unit
      sequence -(AlaGly)3-X-Gly-, where X is Asn, Phe, Ser, Val, or Tyr. The proteins
      were overexpressed in Escherichia coli, purified by simple procedures based on
      acid/ethanol precipitation or insolubility in aqueous sodium dodecyl sulfate, and
      processed to form oriented crystalline mats by precipitation from formic acid
      under mechanical shear. X-ray diffraction analyses revealed that the basic
      structures of the -(AlaGly)3-X-Gly- polymers are identical to that previously
      reported for [(AlaGly)3-GluGly]36, [Krejchi, M.T., Atkins, E.D.T., Waddon, A.J.,
      Fournier, M.J., Mason, T.L., and Tirrell, D.A. (1994) Science 265, 1427-1432],
      with the oligoalanylglycine segments forming antiparallel beta-sheets and the
      substituted amino acids occurring within three-residue folds at the lamellar
      surfaces. The X-ray diffraction signals for each member of the family index on an
      orthorhombic unit cell; the a-axis (hydrogen bond direction) and c-axis (chain
      direction) spacings remain invariant but the b-axis (sheet stacking direction)
      spacing increases with increasing volume of the substituted amino acid. The
      results obtained from a variant with alternating Glu and Lys substitution at the
      X position, together with the results previously reported for poly(L
      alanylglycine) [Panitch, A., Matsuki, K., Cantor, E.J., Cooper, S.J., Atkins,
      E.D.T., Fournier, M.J., Mason, T.L., and Tirrell, D.A. (1997) Macromolecules 30,
      42-49] are included for comparison. The average intersheet stacking distance
      (b/2) increases linearly with the volume of the amino acid inserted at position
      X. Because the chain-folded lamellar architecture adopted by these periodic
      polypeptides accommodates a wide range of residues differing in charge, steric
      bulk, and hydrophobicity, these results illustrate a new approach to the
      engineering of intermolecular interactions in polymeric solids.

PMID- 9276693
TI  - Identification of actin-binding proteins from sea urchin eggs by F-actin affinity
      column chromatography.
AB  - Novel F-actin binding proteins of sea urchin eggs were searched for in order to
      study regulation of the actin cytoskeleton during fertilization and cell
      division. An extract of unfertilized eggs was analyzed by F-actin column
      chromatography. Several previously characterized F-actin-modulating proteins such
      as spectrin, myosin, and fascin bound to the column. The eluates from the column
      also contained proteins having apparent molecular weights of 225K, 150K, 70K,
      60K, 45K, 40K, 38K, 36K, 34K, 20K, and 15K, which were thought to be novel
      cytoskeletal proteins judging from their molecular weights and non-reactivity to
      antibodies against previously characterized F-actin-modulating proteins. Most of
      the proteins in the F-actin column eluates co-sedimented with F-actin. Partial
      amino acid sequences of the peptides derived from the 45K and 40K proteins showed
      that these proteins are homologous to Arp3 and Arp2 subfamilies of actin-related
      proteins, respectively. The 150K protein seemed to be an unconventional myosin,
      that belongs to myosin VI subfamily. Amino acid sequences of two fragments from
      the 60K protein showed homology to that of coronin. The 150K protein was
      localized by immunofluorescence microscopy to the cleavage furrows in both whole
      cell sample and isolated cortex of dividing eggs. The 70K protein was uniformly
      localized in the cortical layer in the whole egg, but weak staining of the
      cleavage furrow region with the antiserum was observed in the isolated cortex.
      The 60K protein was localized to both the bulk cortical layer and the cleavage
      furrow, but the modes of localization were different.

PMID- 9276694
TI  - Initial stage of DNA-electrotransfer into E. coli cells.
AB  - The mechanism of electrotransfer of DNA into Escherichia coli cells was
      investigated under conditions optimal for genetic transformation or transfection.
      Simple mixing in 10% polyethylene glycol 6000 did not cause binding of DNA to the
      recipient bacteria. When subjected to a high electric field, however, 90-98% of
      the input plasmid or phage DNAs were complexed with the cells. By application of
      the electric field, a significant amount of biotin-labeled DNA was bound onto the
      recipient surface, as detected by fluorescein isothiocyanate coupled avidin. When
      subjected to a high voltage pulse, DNA molecules were rapidly attracted toward
      the anode. Concurrently, the electric field induced the orientation of bacterial
      cells, along the field lines and their movement toward the anode. Since the
      bacterial movement was relatively slow, a substantial fraction of DNA molecules
      must strike the cathode-facing end or side of the recipient cells. Irrespective
      of the high efficiency of DNA transformation, the voltage pulse did not induce
      release of alkaline phosphate and beta-galactosidase. The electrotransferred DNA
      first remained sensitive to Tris-EDTA treatment, and became refractory to
      spheroplasting only after incubation at 37 degrees C. These results indicate that
      the infecting DNA is electrophoretically plugged to the outer membrane loosened
      by the voltage pulse.

PMID- 9276695
TI  - Molecular cloning of Ca2+/calmodulin-dependent protein kinase kinase beta.
AB  - Calmodulin-dependent protein kinase IV (CaM-kinase IV), which plays crucial roles
      in the functioning of Ca2+ in the central nervous and immune systems, is markedly
      activated upon phosphorylation through the action of CaM-kinase kinase. Our
      previous immunotitration analysis suggested the existence of an isoform different
      from CaM-kinase kinase alpha, the beta isoform, in rat brain [Okuno, S., Kitani,
      T., and Fujisawa, H. (1996) J. Biochem. 119, 1176-1181]. In the present study,
      cDNA for CaM-kinase kinase beta was cloned from a rat cerebellar cDNA library.
      The coded protein consisted of 587 amino acids with a molecular weight of 64,445.
      Western blot analysis revealed that CaM-kinase kinase beta significantly existed
      only in the brain. The enzyme was not significantly detected in the retina where
      CaM-kinase kinase alpha exists.

PMID- 9276696
TI  - Staging and management of colorectal cancer.
AB  - The management of colorectal cancer becomes ever more complex. Rational decision
      making depends on knowledge of the apparent stage of the disease in the
      individual patient. Many decisions require input from the patient, who therefore
      must be party to all relevant information, including any that is predictive of
      the likely outcome of the disease and the effects of treatment. The process of
      staging once required only pathologic information gleaned from the surgical
      specimen. Later clinical information was often added to produce a more
      practically useful prediction of outcome; necessarily, the staging process,
      whether pathologic or clinicopathologic, could only be completed postoperatively.
      Today there is a momentum toward preempting this process through the use of
      scanning and other modalities, so "staging" information can be used when planning
      primary treatment, including neoadjuvant therapy and surgery. The ultimate
      staging system would comprise just two reliably predictive patient categories:
      those expected to survive and those destined to die. So far no system has
      approached that "ideal." Given such a system, therapeutic and research efforts
      could be concentrated on reversing the outcome for those predicted to die.

PMID- 9276697
TI  - Recent advances in molecular genetics of colorectal cancer.
AB  - Advances in molecular biology have identified two important genes responsible for
      the hereditary colorectal cancers familial adenomatous polyposis (FAP) and
      hereditary nonpolyposis colorectal cancer. They are the APC gene and mismatch
      repair genes. The role of these genes in colorectal carcinogenesis has been
      studied intensively. The adenoma-carcinoma sequence was initially proposed by
      Vogelstein, and the multistep carcinogenesis theory is now well accepted. The
      various functions of the APC gene have been elucidated. APC genes are considered
      to play a role in shedding of the epithelial cells into the lumen. The mechanism
      behind formation of a unicryptal adenoma is now better understood. Adenoma
      formation is a monoclonal event with two hits of the APCgene. There is no zonal
      extension of the proliferative zone in the background colonic mucosa of FAP
      patients. In addition to the adenoma-carcinoma sequence, there seem to be various
      carcinogenetic pathways in the development of colorectal cancer. A depressed type
      of early cancer was recently found by the use of magnifying endoscopy. The
      incidence of K-ras mutation was extremely low in this group of early cancers.
      Some of the minute cancers show the p53mutation before the occurrence of APC
      mutation. Cancers of microsatellite mutator phenotype show exaggerated genomic
      instability at simple repeat sequences, such as TGFbetaRII. These genes may play
      a suppressor role in a p53 independent pathway of colorectal carcinogenesis. We
      are now in an exciting era of this progressing field of science. This genetic
      information may be more widely applicable clinically in the near future (e.g.,
      for presymptomatic diagnosis, selection of patients for the most appropriate
      treatments, and assessment of malignant potential).

PMID- 9276698
TI  - Future role of the pathologist in reporting colorectal cancer.
AB  - A pathology report on a surgical specimen of colorectal cancer has prognostic
      implications and is assuming increasing importance in relation to decisions
      regarding postoperative adjuvant therapy. The classic pathologic report is a
      static description of the extent of spread within the surgical specimen. The
      clinician, on the other hand, needs to know how far the tumor has spread in the
      patient. For the radiotherapist the report on rectal cancer must include a
      detailed account of anatomic location and spread, including relations to
      peritoneum and extent of mesorectal involvement. The oncologist aims to improve
      survival of patients undergoing "curative" surgery. Untreated, a subset of such
      patients die of metastatic disease, occult hepatic metastases being present at
      the time of surgery. An estimate of the risk of micrometastatic disease requires
      a prognostic classification utilizing independent pathobiologic variables.
      Reporting of colorectal cancer needs to become more closely tailored to clinical
      endpoints relevant to therapeutic decision-making. This paper looks critically at
      current practice and future directions.

PMID- 9276699
TI  - Endoscopic diagnosis and treatment of early colorectal cancer.
AB  - Colorectal adenomas and early cancers are grossly classified into three groups:
      protruded, flush or slightly elevated (so-called flat adenomas), and depressed.
      Protruded lesions and flat adenomas are not invasive until they are rather large,
      whereas depressed lesions can invade the submucosa even when very small. It is
      not difficult to detect protruded and flat adenomas, but depressed carcinomas are
      often overlooked. Keys to the detection of depressed carcinomas are a slight
      color change, bleeding spots, interruptions of the capillary network pattern,
      slight deformation of the colonic wall, shape change of the lesion with
      insufflation and deflation of air, and interruption of the innominate grooves by
      the lesion. Spraying of indigo carmine dye helps to clarify the lesions. Pit
      pattern analysis with magnifying colonoscopy is useful for diagnosis of early
      colorectal cancer. Pit pattern analysis and histologic examination suggest that
      depressed carcinomas probably have arisen de novo, without going through an
      adenomatous step. Some adenomas appear at first to have a depression, but such
      cancer-mimicking adenomas with pseudodepression must be distinguished from
      depressed carcinomas because they are quite different in nature. Protruded and
      flat adenomas can usually be removed with polypectomy or hot biopsy techniques.
      Depressed carcinomas are treated with an endoscopic mucosal resection (EMR)
      technique; but when they massively invade the submucosa, surgical resection is
      indicated. Some neoplastic lesions, which we call laterally spreading tumors,
      extensively and circumferentially spread along the colonic wall, although they
      are short in height. They tend to have a rather benign nature despite their large
      size; therefore EMR or a piecemeal EMR method is indicated.

PMID- 9276700
TI  - Laparoscopic versus open surgery for colorectal cancer.
AB  - There are three basic roles of laparoscopic surgery for patients with colorectal
      cancer. First, although infrequently needed prior to therapy, diagnostic or
      staging laparoscopy may be valuable in certain colorectal cancer patients.
      Second, the laparoscopic approach may offer several attractive features for the
      palliative management of patients with incurable colorectal cancer. Finally,
      although this issue is the most controversial, there are theoretic but unproved
      advantages of using laparoscopic techniques for curative colorectal cancer
      therapy. The concerted efforts of surgical oncologists and their colleagues must
      prove this theory in well constructed trials.

PMID- 9276701
TI  - Local excision of rectal cancer.
AB  - The prospect of treating a rectal cancer often leads to significant fear among
      patients because of the possibility of a permanent colostomy. Although radical
      resection, in particular abdominoperineal resection, has been used effectively
      for rectal cancer treatment, other techniques such as local excision with or
      without adjuvant therapy have been used with significantly less morbidity than
      that of the abdominoperineal resection, with excellent cure rates. There are
      essentially three local excision techniques that can be used to remove a small
      rectal cancer completely. Selection criteria are critical for choosing the
      appropriate patient for these techniques. Tumors must be less than 4 cm in
      diameter and take up less than 40% of the rectal wall circumference. They also
      need to be relatively close to the dentate line and have no evidence of any
      invasion into the mesorectum or perirectal nodes. Preoperative staging with
      endorectal ultrasonography, computed tomography, and digital examination helps
      select appropriate patients. Retrospective series have shown significant success
      using local excision techniques, with local recurrence rates ranging from 0% to
      11% for early-stage lesions. Prospective series have shown similar recurrence
      rates. Postoperative function with or without adjuvant therapy has not been
      adequately documented along with quality of life and must be part of any future
      reports on local excision techniques as well as all rectal cancer treatment
      studies. Local excision does, however, seem to provide adequate treatment in well
      selected patients and provides a less morbid alternative to the treatment of
      rectal cancer than radical resection, particularly abdominoperineal resection,
      which obligates the patient to a permanent colostomy.

PMID- 9276702
TI  - Abdominoperineal resection via total mesorectal excision and autonomic nerve
      preservation for low rectal cancer.
AB  - We have examined the results of abdominoperineal resection (APR) for primary
      cancer of the rectum performed in accordance with the principles of total
      mesorectal excision (TME) and autonomic nerve preservation (ANP). TME is defined
      as sharp pelvic dissection under direct vision between the parietal and visceral
      planes of the pelvic fascia. TME results in the resection of all mesorectal
      disease with intact, negative lateral or circumferential margins of resection.
      Statistical analysis was done of survival, local recurrence, and both sexual and
      urinary functions in a prospective database of consecutive patients. Operative
      mortality was 2% (3/148) due to cardiac disease. Overall survival was 60%,
      significantly worse than consecutive patients from the same database who were
      able to undergo sphincter preservation (81%) (p = 0.0003). Poorer survival was
      statistically related to the presence of positive lymph nodes (p = 0.0009).
      Overall, local recurrence rates were 5% (8/148) in patients without distant
      metastases, and 15% to 21% in patients with positive nodes. Positive lymph nodes,
      N2 disease, lymphatic vascular invasion, and perineural invasion were independent
      significant risk factors for local recurrence. Sexual function was preserved in
      approximately 57% of patients undergoing APR versus 85% of patients undergoing
      sphincter preservation. No significant urinary morbidity was encountered. Low
      rectal cancer requiring APR seems to be a disease with more locally advanced
      disease and adverse pathologic features than are seen with mid-rectal cancers
      treatable by low anterior resection. APR when performed in accordance with the
      principles of TME and ANP ensures the greatest likelihood of resecting all
      regional disease while preserving both sexual and urinary functions. Preoperative
      combined modality treatment may be warranted in all T3 or greater low rectal
      cancers.

PMID- 9276703
TI  - Ultra-low anterior resection and coloanal pouch reconstruction for carcinoma of
      the distal rectum.
AB  - Facilitated by an enhanced appreciation for pelvic anatomy and physiology along
      with a better understanding of patterns of rectal cancer spread, great advances
      have been made in our ability to perform restorative resections for an ever
      increasing proportion of mid and distal rectal cancers. Whereas oncologic results
      following a low anterior resection were the principal concern 20 years ago,
      recent efforts have focused on improving functional results as well. Aspirations
      for improved function need to be tempered by the realization that improved
      sphincter-saving rates must follow improved oncologic results rather than
      jeopardize them. Some crucial questions are addressed in this paper: What are the
      variables involved in optimizing the oncologic and functional results of a low
      anterior resection and a coloanal reconstruction? What are the issues involved in
      selecting a particular coloanal reconstruction (straight versus pouch, stapled
      versus handsewn, with or without fecal diversion) for a particular patient? Who
      is not a good candidate for a coloanal reconstruction?

PMID- 9276704
TI  - Importance of extended lymphadenectomy with lateral node dissection for advanced
      lower rectal cancer.
AB  - A total of 448 patients with advanced lower rectal cancer who underwent curative
      wide lymphadenectomy with autonomic nerve preservation were reviewed with respect
      to surgical techniques, operative burdens, node status, survival rate, and mode
      of recurrence. Operative time and blood loss in patients who underwent lateral
      dissection were much greater than those encountered with conventional resection.
      According to the direction of lymphatic spread in patients with Dukes C disease,
      the incidence of upward spread was 94% and lateral spread 27%. The overall
      incidence of lateral metastasis was 14%. The overall 5-year survival was 70%.
      According to the Dukes classification, the 5-year survival rates were 92% for
      Dukes A, 79% for Dukes B, and 55% for Dukes C, whereas it was 43% in patients
      with lateral node metastasis. An analysis of the survival rate was carried out
      with regard to the number of node metastases, direction of lymphatic spread, and
      autonomic nerve preservation. The overall incidence of local recurrence was 9.3%
      and amounted to 16.0% in patients with Dukes C disease. The case of advanced
      lower rectal cancer was characterized by positive lymph nodes or circular lesions
      around the circumference (both diagnosed by endorectal ultrasonography). We
      recommend extended lymphadenectomy with lateral node dissection, as it preserves
      the autonomic nerve.

PMID- 9276705
TI  - Clinicopathological staging and management of colorectal cancer. Perioperative
      radiation therapy.
AB  - The use of radiotherapy, as a complementary procedure prior to surgery for
      immobile, nonresectable, rectal cancers or as an adjuvant treatment in patients
      with mobile rectal cancer is discussed. Locally nonresectable rectal cancer can
      be resected after prolonged preoperative radiotherapy. The proportion of patients
      possible to cure after this prolonged treatment is not precisely known, mainly
      due to differences in the criteria for nonresectability. Literature data show
      that between 35% and 80% can undergo resection for cure, and 25% to 40% can be
      long-term disease-free survivors. Moreover, the role of chemotherapy in
      combination with radiotherapy in this group is not yet settled owing to the lack
      of convincing data from randomized trials. Data from the literature clearly
      indicate that preoperative radiotherapy in patients with mobile rectal cancer is
      superior to postoperative irradiation. Provided the dose is sufficiently high, a
      relative reduction in the local recurrence rate of 60% in combination with
      "standard surgery" is to be expected, and this reduction increases long-term
      survival. An important question is the role of adjuvant radiotherapy together
      with "more optimized surgery." It is likely that the local recurrence rate will
      decrease with the same magnitude, indicating that local recurrent rectal cancer
      in patients with mobile rectal cancer can be more or less eradicated if optimized
      surgery is combined with preoperative radiotherapy. With proper timing and
      treatment technique, the adverse effects on surrounding tissues, both immediate
      and late, can be kept acceptably low.

PMID- 9276706
TI  - Resection of liver metastases of colorectal carcinoma.
AB  - Hepatic metastasis of colorectal cancer is a life-threatening prognostic factor.
      The present review revealed that hepatic resection is the best treatment
      modality, although the overall survival rate after hepatectomy for metastatic
      colorectal cancer is still low (20-40%). Various prognostic factors analyzed by
      many authors are controversial. The number of hepatic metastases and the surgical
      margin were the most important prognostic factors, as seen in 10 papers
      previously reported including our data. A clear surgical margin is achievable,
      but the prognosis of patients with four or more metastatic nodules in the liver
      remains poor. Repeat hepatectomy is also evaluated and is believed by many
      surgeons to have acceptable mortality. It improved survival to a certain extent.
      Analysis of the biologic characteristics of primary and metastatic tumors is
      extremely important and is urgently indicated.

PMID- 9276707
TI  - Chemotherapy for the treatment of patients with metastatic colorectal cancer: an
      overview.
AB  - Approximately 50% of patients with colorectal cancer develop locally recurrent or
      distant metastatic disease during the course of their illness and eventually die.
      Since the 1950s the mainstay of treatment for patients in need of palliative
      therapy has been and continues to be the fluoropyrimidines. When 5-fluorouracil
      (5-FU) was first introduced into the clinic it was used as a single agent given
      by rapid intravenous injection. Results with this drug have been disappointing,
      with response rates consistently low, usually of brief duration, and with little
      or no impact on survival. During the 1970s and 1980s, multidrug regimens were
      evaluated with little or no improvement in outcome. More recently, our
      understanding of the metabolism, pharmacology, and the mechanisms of action as
      well as the potential mechanisms of resistance to 5-FU has led to its more
      rational use. This knowledge has resulted in the design of treatment programs
      with improved therapeutic effects by changing its route of administration,
      combining it with biochemical modulators and using it in conjunction with other
      chemotherapeutic agents. These strategies have created new optimism for improved
      results with less toxicity. More potent inhibitors of thymidylate synthase (TS)
      such as tomudex and trimetrexate have been developed and are currently being
      evaluated in the clinic either alone or in combination with 5-FU. Semisynthetic
      topoisomerase inhibitors such as irinotecan have shown encouraging results as
      first-line therapy, in combination with 5-FU or as salvage therapy.

PMID- 9276708
TI  - Comparative study of the early postoperative course and complications in patients
      undergoing Billroth I and Billroth II gastrectomy.
AB  - Distal gastric resection can be followed by reconstruction according to the
      Billroth I (BI) or Billroth II (BII) techniques. The aim of this study was to
      compare the early postoperative results and complications of patients undergoing
      BI and those undergoing BII resection. Eighty-eight patients operated during the
      years 1991 to 1994 underwent distal gastric resection (41 had BI, and 43 had BII
      resections). The indications for BI resections were gastric tumors in 39 patients
      (95%) and duodenal ulcer in 2 (5%). The indications for BII resection were
      malignancy in 28 patients (65%) and duodenal ulcer disease in 15 (35%). The
      average duration of the procedure was 147 +/- 28 minutes for the BI resection and
      175 +/- 38 minutes for the BII resection (p < 0.05). No patient in the BI group
      developed anastomic leakage. Two patients who underwent BII resection developed
      duodenal stump leakage (4.7%). Relaparotomy was indicated in five patients, two
      from the BI group (malignant cells in the resection margins) and three from the
      BII group (one due to duodenal stump leakage and two for bleeding). There was no
      postoperative mortality in the BI group. The postoperative mortality in the BII
      group was 7.1% (p < 0.05). The average proximal gastric resection margins were
      significantly smaller in the BI group than in the BII group (3.65 +/- 2.83 cm and
      5.18 +/- 2.57 cm, respectively; p < 0. 05). The number of lymph nodes found in
      the resected specimen did not differ significantly between the two groups.
      Recurrent tumor at the gastric remnant developed in two patients in the BI group
      but not in the BII group. The results of our study revealed that the BI procedure
      is accompanied by significantly lower postoperative complication and mortality
      rates than the BII procedure in cases of gastric malignancy. BI resection
      performed for malignancy seems to achieve smaller proximal gastric resection
      margins, which may influence the recurrence rate.

PMID- 9276709
TI  - p53 hot-spot mutational analysis in advanced Western gallbladder carcinoma.
AB  - In gallbladder carcinoma, studies on the prime target of genetic alterations and
      gene therapy in human gallbladder malignancies, the p53 tumor suppressor gene,
      have been focusing on this gene's immunohistochemical detection. From November
      1991 to October 1993, seven patients suffering from gallbladder carcinoma
      underwent surgical resection. Cancerous and normal liver tissues were obtained
      immediately after surgery, snap-frozen in liquid nitrogen, and stored at -80
      degrees C for immunohistochemistry and DNA isolation. Exons 5, 6, 7, and 8 of the
      p53 gene were completely sequenced following polymerase chain reaction (PCR)
      amplification of a 1574-bp fragment. Missense mutations were detected in the
      cancerous tissues of two patients: one transition each on codons 134 (Phe-->Leu)
      and 146 (Trp-->Arg). Immunohistochemical p53 staining was positive in the latter
      patient only. This is the first report on sequence analysis and mutagenesis of
      the p53 gene in Caucasian patients with gallbladder cancer. Both mutations were
      transitions and seem to represent a rather rare event. The possible impact of p53
      mutagenesis on gallbladder tumorigenesis requires evaluation in larger studies.

PMID- 9276710
TI  - Close correlation between increased sialyl-Lewisx expression and metastasis in
      human gastric carcinoma.
AB  - Expression of sialyl-Lewisx (sLex) antigen was studied immunohistochemically in
      110 resected human gastric carcinomas using an anti-sLex monoclonal antibody.
      Lymph node, liver, and peritoneal metastases were clearly more prevalent in
      tumors expressing high levels of sLex than in those with no or low-level sLex
      expression. No correlation was found between sLex expression and histologic grade
      or histologic type of the Lauren classification. Among the tumors with lymph node
      metastasis, 44% expressed high levels of sLex in both the primary tumor and
      involved lymph nodes, and 14% of the metastatic lesions demonstrated increased
      sLex expression. The 5-year survival rate of the patients undergoing complete
      (R0) gastric resections was 60% in the sLex high-expression group, which was
      significantly lower than that of the sLex low-expression group (81%) and of the
      no-expression group (87%) (p < 0.05). These results suggest that high-level sLex
      expression is related to both an increased risk of metastasis and poor prognosis
      in gastric cancer patients.

PMID- 9276711
TI  - Quality of life of patients with gastric adenocarcinoma after curative
      gastrectomy.
AB  - Quality of life (QOL) was evaluated in 162 patients having radical gastrectomy
      for cancer. The results showed that more than half of the patients had a good
      appetite; they consumed a normal diet and a normal volume of food. Approximately
      60% of the patients had weight loss of more than 5 kg. Patients who underwent a
      total gastrectomy had poor tolerance of normal food and frequent eating and body
      weight loss versus those who had a subtotal gastrectomy. Patients who underwent
      Billroth II reconstruction after a distal subtotal gastrectomy lost more body
      weight than those with a Billroth I anastomosis. The extent of lymphadenectomy
      did not influence the QOL. Patients under 65 years of age had a better QOL.
      Nearly all patients had normal work and daily living activities. Some patients
      appeared to lack energy or had a period of anxiety or depression. These data
      indicate that radical gastrectomy can be performed with an acceptable QOL for a
      potentially curable gastric carcinoma.

PMID- 9276712
TI  - Generation and phenotype of a transgenic knockout mouse lacking the mercurial
      insensitive water channel aquaporin-4.
AB  - Aquaporin-4 (AQP4) is a mercurial-insensitive, water-selective channel that is
      expressed in astroglia and basolateral plasma membranes of epithelia in the
      kidney collecting duct, airways, stomach, and colon. A targeting vector for
      homologous recombination was constructed using a 7-kb SacI AQP4 genomic fragment
      in which part of the exon 1 coding sequence was deleted. Analysis of 164 live
      births from AQP4[+/-] matings showed 41 [+/+], 83 [+/-], and 40 [-/-] genotypes.
      The [-/-] mice expressed small amounts of a truncated AQP4 transcript and lacked
      detectable AQP4 protein by immunoblot analysis and immunocytochemistry. Water
      permeability in an AQP4-enriched brain vesicle fraction in [+/+] mice was high
      and mercurial insensitive, and was decreased by 14-fold in [-/-] mice. AQP4
      deletion did not affect growth or tissue morphology at the light microscopic
      level. Northern blot analysis showed that tissue-specific expression of AQPs 1,
      2, 3, and 5 was not affected by AQP4 deletion. Maximum urine osmolality after a
      36-h water deprivation was (in mosM, n = 15) [+/+] 3,342+/-209, [+/-] 3, 225+/
      167, and [-/-] 2,616+/-229 (P < 0.025), whereas urine osmolalities before water
      deprivation did not differ among the genotypes. Rotorod analysis of 35- 38-d-old
      mice revealed no differences in neuromuscular function (performance time in s, n
      = 8): [+/+] 297+/-25, [+/-] 322+/-28, [-/-] 288+/-37. These results indicate that
      AQP4 deletion in CD1 mice has little or no effect on development, survival,
      growth, and neuromuscular function, but produces a small defect in urinary
      concentrating ability consistent with its expression in the medullary collecting
      duct.

PMID- 9276713
TI  - Intercellular adhesion molecule-1 deficiency prolongs survival and protects
      against the development of pulmonary inflammation during murine lupus.
AB  - One of the characteristic features of the lupus syndrome in humans and mice is
      the organ-specific accumulation of leukocytes within a variety of different
      tissues; however, the etiology of this phenomenon remains unclear. The work
      presented here determined the role of intercellular adhesion molecule (ICAM)-1 in
      the development of pulmonary leukocyte accumulation by generating MRL/MpJ-Faslpr
      mice that are genetically deficient in this critical adhesion molecule.
      Interestingly, these MRL/MpJ-Faslpr ICAM-1 knockout mice exhibit prolonged
      survival times compared to littermates expressing ICAM-1. We have determined that
      lack of ICAM-1 completely abrogates the development of pulmonary inflammation but
      does not prevent the development of autoantibodies, lymphadenopathy, and
      glomerulonephritis. Furthermore, the lack of pulmonary inflammation was found to
      be due to decreased migration of leukocytes to the lung rather than decreased in
      situ proliferation of cells.

PMID- 9276714
TI  - Role of NFkappaB in the mortality of sepsis.
AB  - Binding activity for nuclear factor kappa B (NFkappaB) consensus probes was
      studied in nuclear extracts from peripheral blood mononuclear cells of 15 septic
      patients (10 surviving and 5 not surviving). Nonsurvivors could be distinguished
      from survivors by an increase in NFkappaB binding activity during the observation
      period (P < 0.001). The increase in NFkappaB binding activity was comparable to
      the APACHE-II score as a predictor of outcome. Intravenous somatic gene transfer
      with an expression plasmid coding for IkappaBalpha was used to investigate the
      role of members of the NFkappaB family in a mouse model of endotoxemia. In this
      model, increased NFkappaB binding activity was present after injection of LPS.
      Intravenous somatic gene transfer with IkappaBalpha given before LPS attenuated
      renal NFkappaB binding activity and increased survival. Endothelial cells and
      monocytes/macrophages were the major target cells for somatic gene transfer,
      transfected with an average transfection efficiency of 20-35%. Tissue factor, a
      gene under regulatory control of NFkappaB, was induced by LPS. Somatic gene
      transfer with a reporter plasmid containing the functional tissue factor promoter
      demonstrated NFkappaB-dependent stimulation by LPS. Intravenous somatic gene
      transfer with IkappaBalpha reduced LPS-induced renal tissue factor expression,
      activation of the plasmatic coagulation system (decrease of thrombin-antithrombin
      III complexes) and renal fibrin/fibrinogen deposition. Somatic gene transfer with
      an expression plasmid with tissue factor cDNA in the antisense direction (in
      contrast to sense or vector alone) also increased survival. Furthermore,
      antisense tissue factor decreased renal tissue factor expression and the
      activation of the plasmatic coagulation system.

PMID- 9276715
TI  - Bone marrow transplantation reproduces the tristetraprolin-deficiency syndrome in
      recombination activating gene-2 (-/-) mice. Evidence that monocyte/macrophage
      progenitors may be responsible for TNFalpha overproduction.
AB  - Tristetraprolin-deficient [TTP (-/-)] mice exhibit a complex syndrome of myeloid
      hyperplasia, cachexia, dermatitis, autoimmunity, and erosive arthritis. Virtually
      the entire syndrome can be prevented by the repeated injection of anti-TNFalpha
      antibodies (Taylor, G.A., E. Carballo, D.M. Lee, W.S. Lai, M.J. Thompson, D.D.
      Patel, D.I. Schenkman, G.S. Gilkeson, H.E. Broxmeyer, B.F. Haynes, and P.J.
      Blackshear. 1996. Immunity. 4:445-454). In the present study, we transplanted
      bone marrow from TTP (-/-) and (+/+) mice into recombination activating gene-2 (
      /-) mice. After a lag period of several months, marrow transplantation from the (
      /-) but not the (+/+) mice resulted in the full syndrome associated with TTP
      deficiency, suggesting that hematopoietic progenitors are responsible for the
      development of the syndrome. Western blot analysis of supernatants from cultured
      TTP-deficient macrophages derived from the peritoneal cavity or bone marrow of
      adult TTP (-/-) mice, or from fetal liver, demonstrated an increased accumulation
      of TNFalpha after stimulation with LPS compared to control cells, and also
      increased accumulation of TNFalpha mRNA. This difference was not observed with
      cultured fibroblasts or T and B lymphocytes. These data suggest that macrophages
      are among the cells responsible for the effective excess of TNFalpha that leads
      to the pathology reported in TTP (-/-) animals, and that macrophage progenitors
      may be involved in the transplantability of this syndrome.

PMID- 9276717
TI  - Transcriptional targeting of replication-defective adenovirus transgene
      expression to smooth muscle cells in vivo.
AB  - Gene transfer using replication-defective adenoviruses (RDAd) holds promise for
      the treatment of vascular proliferative disorders, but is potentially limited by
      the capacity of these viruses to infect multiple cell lineages. We have generated
      an RDAd vector, designated AdSM22-lacZ, which encodes the bacterial lacZ reporter
      gene under the transcriptional control of the smooth muscle cell (SMC)-specific
      SM22alpha promoter. Here, we show that in vitro AdSM22-lacZ programs expression
      of the lacZ reporter gene in primary rat aortic SMCs and immortalized A7r5 SMCs,
      but not in primary human umbilical vein endothelial cells (HUVECs) or NIH 3T3
      cells. Consistent with these results, after intraarterial administration of
      AdSM22-lacZ to control and balloon-injured rat carotid arteries, beta
      galactosidase activity was detected within SMCs of the tunica media and
      neointima, but not within endothelial or adventitial cells. Moreover, intravenous
      administration of AdSM22-lacZ did not result in lacZ gene expression in the liver
      or lungs. Finally, we have shown that direct injection of AdSM22-lacZ into SMC
      containing tissues such as the ureter and bladder results in high-level transgene
      expression in visceral SMCs. Taken together, these results demonstrate that
      transgene expression after infection with an RDAd vector can be regulated in an
      SMC lineage-restricted fashion by using a transcriptional cassette containing the
      SMC-specific SM22alpha promoter. The demonstration of an efficient gene delivery
      system targeted specifically to SMCs provides a novel means to restrict
      expression of recombinant gene products to vascular or visceral SMCs in vivo.

PMID- 9276716
TI  - Platelet activation In mice and human Helicobacter pylori infection.
AB  - Extracts of Helicobacter pylori (HP) have been shown to induce leukocyte adhesion
      in mesenteric venules, but the effects of HP infection on gastric microvessels
      are unknown. Inflammatory cell interactions in the gastric microcirculation were
      studied by intravital videomicroscopy in mice inoculated with either saline or
      fresh isolates of HP. Platelet aggregates were detected and quantified in murine
      portal blood, while endothelial P-selectin expression was determined using the
      dual radiolabeled mAb technique. Platelet activation and aggregation were studied
      in HP-infected patients and controls by measuring the platelet-aggregate ratio
      and platelet P-selectin expression. HP infection induced a marked increase in the
      flux of rolling leukocytes and the appearance of platelet and leukocyte- platelet
      aggregates in murine gastric venules. The HP-induced rolling and platelet
      aggregate formation was abrogated by mAbs against L- or P-, but not E- selectin.
      Endothelial cell expression of P-selectin was not altered, but platelet P
      selectin expression was enhanced in HP-infected mice. Circulating platelet
      aggregates and activated platelets were also detected in HP-infected patients.
      These findings indicate that platelet activation and aggregation contribute to
      the microvascular dysfunction and inflammatory cell recruitment associated with
      HP infections.

PMID- 9276718
TI  - The critical early proinflammatory events associated with idiopathic pneumonia
      syndrome in irradiated murine allogeneic recipients are due to donor T cell
      infusion and potentiated by cyclophosphamide.
AB  - We have hypothesized that lung damage occurring in the peri-bone marrow
      transplant (BMT) period is critical for the subsequent generation of idiopathic
      pneumonia syndrome (IPS), a major complication following human BMT. The
      proinflammatory events induced by a common pre-BMT conditioning regimen,
      cyclophosphamide (Cytoxan(R)) (Cy) and total body irradiation, were analyzed in a
      murine BMT model. Electron microscopy indicated that Cy exacerbated irradiation
      induced epithelial cell injury as early as day 3 after BMT. Allogenicity was an
      important contributing factor to lung injury as measured by lung wet and dry
      weights and decreased specific lung compliance. The most significant pulmonary
      dysfunction was seen in mice receiving both allogeneic T cells and Cy
      conditioning. IPS was associated with an influx of T cells, macrophages, and
      neutrophils early post-BMT. Hydroxyproline levels were not increased, indicating
      that the injury was not fibrotic early post-BMT. As early as 2 h after
      chemoradiation, host macrophages increased in number in the lung parenchyma.
      Continued increases in macrophages occurred if splenic T cells were administered
      with the donor graft. The expression of costimulatory B7 molecules correlated
      with macrophage numbers. Frequencies of cells expressing mRNA for the
      inflammatory proteins TNF-alpha, IL-1beta, and TGFbeta were increased. Cy
      accelerated the upregulation of TGFbeta and increase in host macrophages. The
      exacerbation of macrophage activation and severity of IPS was dependent on
      allogeneic T cells, implicating immune-mediated mechanisms as critical to the
      outcome of IPS. This demonstration of early injury after BMT indicates the need
      for very early therapeutic intervention before lung damage becomes profound and
      irreversible.

PMID- 9276719
TI  - Murine embryonic stem cells without pig-a gene activity are competent for
      hematopoiesis with the PNH phenotype but not for clonal expansion.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) develops in patients who have had a
      somatic mutation in the X-linked PIG-A gene in a hematopoietic stem cell; as a
      result, a proportion of blood cells are deficient in all glycosyl
      phosphatidylinositol (GPI)-anchored proteins. Although the PIG-A mutation
      explains the phenotype of PNH cells, the mechanism enabling the PNH stem cell to
      expand is not clear. To examine this growth behavior, and to investigate the role
      of GPI-linked proteins in hematopoietic differentiation, we have inactivated the
      pig-a gene by homologous recombination in mouse embryonic stem (ES) cells. In
      mouse chimeras, pig-a- ES cells were able to contribute to hematopoiesis and to
      differentiate into mature red cells, granulocytes, and lymphocytes with the PNH
      phenotype. The proportion of PNH red cells was substantial in the fetus, but
      decreased rapidly after birth. Likewise, PNH granulocytes could only be
      demonstrated in the young mouse. In contrast, the percentage of lymphocytes
      deficient in GPI-linked proteins was more stable. In vitro, pig-a- ES cells were
      able to form pig-a- embryoid bodies and to undergo hematopoietic (erythroid and
      myeloid) differentiation. The number and the percentage of pig-a- embryoid bodies
      with hematopoietic differentiation, however, were significantly lower when
      compared with wild-type embryoid bodies. Our findings demonstrate that murine ES
      cells with a nonfunctional pig-a gene are competent for hematopoiesis, and give
      rise to blood cells with the PNH phenotype. pig-a inactivation on its own,
      however, does not confer a proliferative advantage to the hematopoietic stem
      cell. This provides direct evidence for the notion that some additional factor(s)
      are needed for the expansion of the mutant clone in patients with PNH.

PMID- 9276720
TI  - Bombesin-induced gastrin release from canine G cells is stimulated by Ca2+ but
      not by protein kinase C, and is enhanced by disruption of rho/cytoskeletal
      pathways.
AB  - Isolated canine G cells in primary culture have been used to study calcium,
      protein kinase C (PKC), and rho/cytoskeletal-dependent intracellular pathways
      involved in bombesin- stimulated gastrin release. A method to obtain highly
      purified G cells by culture (64% G cells) after flow cytometry on elutriated
      fractions of cells from digested canine gastric antral mucosa has been developed.
      Pretreatment of G cells with thapsigargin (10(-8)-10(-6) M) and release
      experiments in Ca2+-containing or -depleted media showed that influx of Ca2+ into
      the cells and not acute release from intracellular stores plays an important role
      in bombesin-stimulated gastrin release. Inhibition of PKC by the specific
      inhibitor GF 109 203X did not affect bombesin-stimulated release. Rho, a small
      GTP-binding protein that regulates the actin cytoskeleton, is specifically
      antagonized by Clostridium botulinum C3 exoenzyme. C3 (10 microg/ml) enhanced
      basal and bombesin-stimulated gastrin release by 315 and 266%, respectively. The
      importance of the cytoskeleton for regulation of gastrin release was emphasized
      by a more pronounced release of gastrin when the organization of the actin
      cytoskeleton was disrupted by cytochalasin D (5 x 10(-)7 and 10(-)6 M).
      Wortmannin, a potent inhibitor of phosphoinositide-3-kinase, did not alter
      bombesin-stimulated gastrin release. Thus, it is concluded that bombesin-induced
      gastrin release from canine G cells is stimulated by Ca2+ but not by PKC, and is
      enhanced by disruption of rho/cytoskeletal pathways.

PMID- 9276721
TI  - Angiotensin II stimulates expression of the chemokine RANTES in rat glomerular
      endothelial cells. Role of the angiotensin type 2 receptor.
AB  - Glomerular influx of monocytes/macrophages (M/M) occurs in many immune- and non
      immune-mediated renal diseases. The mechanisms targeting M/M into the glomerulus
      are incompletely understood, but may involve stimulated expression of chemokines.
      We investigated whether angiotensin II (ANG II) induces the chemokine RANTES in
      cultured glomerular endothelial cells of the rat and in vivo. ANG II stimulated
      mRNA and protein expression of RANTES in cultured glomerular endothelial cells.
      The ANG II-induced RANTES protein was chemotactic for human monocytes.
      Surprisingly, the ANG II-stimulated RANTES expression was transduced by AT2
      receptors because the AT2 receptor antagonists PD 123177 and CGP-42112A, but not
      an AT1 receptor blocker, abolished the induced RANTES synthesis. Intraperitoneal
      infusion of ANG II (500 ng/h) into naive rats for 4 d significantly stimulated
      glomerular RANTES mRNA and protein expression compared with solvent-infused
      controls. Immunohistochemistry revealed induction of RANTES protein mainly in
      glomerular endothelial cells and small capillaries. Moreover, ANG II- infused
      animals exhibited an increase in glomerular ED-1- positive cells compared with
      controls. Oral treatment with PD 123177 (50 mg/liter drinking water) attenuated
      the glomerular M/M influx without normalizing the slightly elevated systolic
      blood pressure caused by ANG II infusion, suggesting that the effects on blood
      pressure and RANTES induction can be separated. We conclude that the vasoactive
      peptide ANG II may play an important role in glomerular chemotaxis of M/M through
      local induction of the chemokine RANTES. The observation that the ANG II-
      mediated induction of RANTES is transduced by AT2 receptors may influence the
      decision as to which substances might be used for the therapeutic interference
      with the activity of the renin-angiotensin system.

PMID- 9276722
TI  - A novel polymorphism of FcgammaRIIIa (CD16) alters receptor function and
      predisposes to autoimmune disease.
AB  - A novel polymorphism in the extracellular domain 2 (EC2) of FcgammaRIIIA affects
      ligand binding by natural killer (NK) cells and monocytes from genotyped
      homozygous normal donors independently of receptor expression. The
      nonconservative T to G substitution at nucleotide 559 predicts a change of
      phenylalanine (F) to valine (V) at amino acid position 176. Compared with F/F
      homozygotes, FcgammaRIIIa expressed on NK cells and monocytes in V/V homozygotes
      bound more IgG1 and IgG3 despite identical levels of receptor expression. In
      response to a standard aggregated human IgG stimulus, FcgammaRIIIa engagement on
      NK cells from V/V (high-binding) homozygotes led to a larger rise in [Ca2+]i, a
      greater level of NK cell activation, and a more rapid induction of activation
      induced cell death (by apoptosis). Investigation of an independently phenotyped
      normal cohort revealed that all donors with a low binding phenotype are F/F
      homozygotes, while all phenotypic high binding donors have at least one V allele.
      Initial analysis of 200 patients with SLE indicates a strong association of the
      low binding phenotype with disease, especially in patients with nephritis who
      have an underrepresentation of the homozygous high binding phenotype. Thus, the
      FcgammaRIIIa polymorphism at residue 176 appears to impact directly on human
      biology, an effect which may extend beyond autoimmune disease characterized by
      immune complexes to host defense mechanisms.

PMID- 9276723
TI  - Developmental changes in water permeability across the alveolar barrier in
      perinatal rabbit lung.
AB  - Lung fluid is reabsorbed rapidly at birth to permit alveolar respiration. We
      reported previously that expression of aquaporins (AQP) 1, 4, and 5 in rat lung
      increased just after birth. The hypothesis was tested that the increased AQP
      expression is associated with increased osmotic water permeability (Pf) between
      the airspace and capillary compartments. Pf was measured in isolated perfused
      fetal and newborn rabbit lungs using a pleural surface fluorescence method
      (Carter, E.P., M.A. Matthay, J. Farinas, and A.S. Verkman. 1996. J. Gen. Physiol.
      108:133-142). In response to perfusate osmolality increase from 300 to 600 mosM,
      initial rates of osmotic equilibration were 1.13+/-0.13 mosM/s at 0-12 h after
      birth, increasing to 1.52+/-0.19 mosM/s at 12-24 h, and 1.83+/-0.10 mosM/s at 24
      84 h. Corresponding Pf values (in cm/s x 10(-2)), computed from d[mosM]/dt and
      alveolar surface-to-volume ratios, were 1.03+/-0.11 (0-12 h), 1.51+/-0.16 (12-24
      h), and 1.88+/-0.09 (24-84 h). Pf was relatively low in prenatal (1.22-1.27,
      fetal days 29 and 31) and adolescent (1.25+/-0.08, 21-d) rabbit lungs. To test
      for involvement of molecular water channels, measurements were made of Arrhenius
      activation energy (Ea), mercurial inhibition, diffusional water permeability
      (Pd), and AQP expression. Temperature-dependence measurements showed a 25%
      decrease in Ea for Pf in lungs < 1 d vs. 4 d. Pf was decreased 30% by 0.5 mM
      HgCl2 in < 1-d lungs and 44% in 4-d lungs. Pd was 1.0 x 10(-)5 cm/s and did not
      change when Pf was increased by 75%. RNase protection assay showed increased
      transcript expression in the first 24 h after birth for rabbit isoforms of AQP1
      and AQP4. These results provide the first functional data on water permeability
      in perinatal lung. The increased water permeability after birth may facilitate
      the maintenance of dry alveoli.

PMID- 9276724
TI  - Structural cues involved in endoplasmic reticulum degradation of G85E and G91R
      mutant cystic fibrosis transmembrane conductance regulator.
AB  - Abnormal folding of mutant cystic fibrosis transmembrane conductance regulator
      (CFTR) and subsequent degradation in the endoplasmic reticulum is the basis for
      most cases of cystic fibrosis. Structural differences between wild-type (WT) and
      mutant proteins, however, remain unknown. Here we examine the intracellular
      trafficking, degradation, and transmembrane topology of two mutant CFTR proteins,
      G85E and G91R, each of which contains an additional charged residue within the
      first putative transmembrane helix (TM1). In microinjected Xenopus laevis
      oocytes, these mutations markedly disrupted CFTR plasma membrane chloride channel
      activity. G85E and G91R mutants (but not a conservative mutant, G91A) failed to
      acquire complex N-linked carbohydrates, and were rapidly degraded before reaching
      the Golgi complex thus exhibiting a trafficking phenotype similar to DeltaF508
      CFTR. Topologic analysis revealed that neither G85E nor G91R mutations disrupted
      CFTR NH2 terminus transmembrane topology. Instead, WT as well as mutant TM1
      spanned the membrane in the predicted C-trans (type II) orientation, and residues
      85E and 91R were localized within or adjacent to the plane of the lipid bilayer.
      To understand how these charged residues might provide structural cues for ER
      degradation, we examined the stability of WT, G85E, and G91R CFTR proteins
      truncated at codons 188, 393, 589, or 836 (after TM2, TM6, the first nucleotide
      binding domain, or the R domain, respectively). These results indicated that G85E
      and G91R mutations affected CFTR folding, not by gross disruption of
      transmembrane assembly, but rather through insertion of a charged residue within
      the plane of the bilayer, which in turn influenced higher order tertiary
      structure.

PMID- 9276725
TI  - Nitric oxide induces heat-shock protein 70 expression in vascular smooth muscle
      cells via activation of heat shock factor 1.
AB  - Current data suggest that nitric oxide (NO) is a double-edged sword that could
      result in relaxation and/or cytotoxicity of vascular smooth muscle cells (SMCs)
      via cGMP- dependent or -independent signal pathways. Stress or heat shock
      proteins (hsps) have been shown to be augmented in arterial SMCs during acute
      hypertension and atherosclerosis, both conditions that are believed to correlate
      with disturbed NO production. In the present study, we demonstrate that NO
      generated from sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine, and
      spermine/nitric oxide complex leads to hsp70 induction in cultured SMCs. Western
      blot analysis demonstrated that hsp70 protein expression peaked between 6 and 12
      h after treatment with SNP, and elevated protein levels were preceded by
      induction of hsp70 mRNA within 3 h. Induction of hsp70 mRNA was associated with
      the activation of heat shock transcription factor 1 (HSF1), suggesting that the
      response was regulated at the transcriptional level. HSF1 activation was
      completely blocked by hemoglobin, dithiothreitol, and cycloheximide, suggesting
      that the protein damage and nascent polypeptide formation induced by NO may
      initiate this activation. Furthermore, SMCs pretreated with heat shock (42
      degrees C) for 30 min were significantly protected from death induced by NO.
      Thus, we provide evidence that NO induces hsp70 expression in SMCs via HSF1
      activation. Induction of hsp70 could be important in protecting SMCs from injury
      resulting from NO stimulation.

PMID- 9276726
TI  - Targeted gene disruption reveals a leptin-independent role for the mouse beta3
      adrenoceptor in the regulation of body composition.
AB  - Targeted disruption of mouse beta3-adrenoceptor was generated by homologous
      recombination, and validated by an acute in vivo study showing a complete lack of
      effect of the beta3-adrenoceptor agonist CL 316,243 on the metabolic rate of
      homozygous null (-/-) mice. In brown adipose tissue, beta3-adrenoceptor
      disruption induced a 66% decrease (P < 0.005) in beta1-adrenoceptor mRNA level,
      whereas leptin mRNA remained unchanged. Chronic energy balance studies in chow
      fed mice showed that in -/- mice, body fat accumulation was favored (+41%, P <
      0.01), with a slight increase in food intake (+6%, NS). These effects were
      accentuated by high fat feeding: -/- mice showed increased total body fat (+56%,
      P < 0.025) and food intake (+12%, P < 0.01), and a decrease in the fat-free dry
      mass (-10%, P < 0.05), which reflects a reduction in body protein content.
      Circulating leptin levels were not different in -/- and control mice regardless
      of diet. The significant shift to the right in the positive correlation between
      circulating leptin and percentage of body fat in high fat-fed -/- mice suggests
      that the threshold of body fat content inducing leptin secretion is higher in -/-
      than in control mice. Taken together, these studies demonstrate that beta3
      adrenoceptor disruption creates conditions which predispose to the development of
      obesity.

PMID- 9276727
TI  - Effects of prolonged hyperinsulinemia on serum leptin in normal human subjects.
AB  - We have studied the effect of prolonged hyperinsulinemia and hyperglycemia on
      serum leptin levels in young nonobese males during 72-h euglycemic
      hyperinsulinemic and hyperglycemic ( approximately 8.5 and 12.6 mM) clamps.
      Hyperinsulinemia increased serum leptin concentrations (by RIA) dose-dependently.
      An increase in serum insulin concentration of > 200 pM for > 24 h was needed to
      significantly increase serum leptin. An increase of approximately 800 pM
      increased serum leptin by approximately 70% over 72 h. Changes in plasma glucose
      concentrations (from approximately 5.0 to approximately 12.6 mM) or changes in
      plasma FFA concentrations (from < 100 to > 1,000 microM) had no effect on serum
      leptin. Serum leptin concentrations changed with circadian rhythmicity. The cycle
      length was approximately 24 h, and the cycle amplitude (peak to trough) was
      approximately 50%. The circadian leptin cycles and the circadian cycles of total
      body insulin sensitivity (i.e., GIR, the glucose infusion rates needed to
      maintain euglycemia during hyperinsulinemic clamping) changed in a mirror image
      fashion. Moreover, GIR decreased between Days 2 and 3 (from 11.4+/-0.2 to 9. 8+/
      0.2 mg/kg min, P< 0.05) when mean 24-h leptin levels reached a peak. In summary,
      we found (a) that 72 h of hyperinsulinemia increased serum leptin levels dose
      dependently; (b) that hyperglycemia or high plasma FFA levels did not affect
      leptin release; (c) that leptin was released with circadian rhythmicity, and (d)
      that 24-h leptin cycles correlated inversely with 24-h cycles of insulin
      sensitivity. We speculate that the close positive correlation between body fat
      and leptin is mediated, at least in part, by insulin.

PMID- 9276728
TI  - Recognition of the immunodominant myelin basic protein peptide by autoantibodies
      and HLA-DR2-restricted T cell clones from multiple sclerosis patients. Identity
      of key contact residues in the B-cell and T-cell epitopes.
AB  - Myelin basic protein (MBP) may be an important autoantigen in multiple sclerosis
      (MS), with the MBP(82-100) region being immunodominant for T cells and
      autoantibodies. The structural requirements for autoantibody recognition were
      compared to those previously defined for MBP-specific T cell clones. MBP
      autoantibodies were affinity-purified from central nervous system lesions of
      11/12 postmortem cases studied. The MBP(83-97) peptide was immunodominant in all
      11 cases since it inhibited autoantibody binding to MBP > 95%. Residues
      contributing to autoantibody binding were located in a 10-amino acid segment (V86
      T95) that also contained the MHC/T cell receptor contact residues of the T cell
      epitope. In the epitope center, the same residues were important for antibody
      binding and T cell recognition. Based on the antibody-binding motif, microbial
      peptides were identified that were bound by purified autoantibodies. Autoantibody
      binding of microbial peptides required sequence identity at four or five
      contiguous residues in the epitope center. Microbial peptides previously found to
      activate T cell clones did not have such obvious homology to MBP since sequence
      identity was not required at MHC contacts. The similar fine specificity of B
      cells and T cells may be useful for tolerance induction to MBP in MS.

PMID- 9276730
TI  - High expression of the chemokine receptor CCR3 in human blood basophils. Role in
      activation by eotaxin, MCP-4, and other chemokines.
AB  - Eosinophil leukocytes express high numbers of the chemokine receptor CCR3 which
      binds eotaxin, monocyte chemotactic protein (MCP)-4, and some other CC
      chemokines. In this paper we show that CCR3 is also highly expressed on human
      blood basophils, as indicated by Northern blotting and flow cytometry, and
      mediates mainly chemotaxis. Eotaxin and MCP-4 elicited basophil migration in
      vitro with similar efficacy as regulated upon activation normal T cells expressed
      and secreted (RANTES) and MCP-3. They also induced the release of histamine and
      leukotrienes in IL-3-primed basophils, but their efficacy was lower than that of
      MCP-1 and MCP-3, which were the most potent stimuli of exocytosis. Pretreatment
      of the basophils with a CCR3-blocking antibody abrogated the migration induced by
      eotaxin, RANTES, and by low to optimal concentrations of MCP-4, but decreased
      only minimally the response to MCP-3. The CCR3-blocking antibody also affected
      exocytosis: it abrogated histamine and leukotriene release induced by eotaxin,
      and partially inhibited the response to RANTES and MCP-4. In contrast, the
      antibody did not affect the responses induced by MCP-1, MCP-3, and macrophage
      inflammatory protein-1alpha, which may depend on CCR1 and CCR2, two additional
      receptors detected by Northern blotting with basophil RNA. This study
      demonstrates that CCR3 is the major receptor for eotaxin, RANTES, and MCP-4 in
      human basophils, and suggests that basophils and eosinophils, which are the
      characteristic effector cells of allergic inflammation, depend largely on CCR3
      for migration towards different chemokines into inflamed tissues.

PMID- 9276729
TI  - Localization of a domain in the FimH adhesin of Escherichia coli type 1 fimbriae
      capable of receptor recognition and use of a domain-specific antibody to confer
      protection against experimental urinary tract infection.
AB  - The FimH subunit of type 1-fimbriated Escherichia coli has been implicated as an
      important determinant of bacterial adherence and colonization of the urinary
      tract. Here, we sought to localize the functionally important domain(s) within
      the FimH molecule and to determine if antibodies against this domain would block
      adherence of type 1-fimbriated E. coli to the bladder mucosa in situ and in vivo
      in an established mouse model of cystitis. We generated translational fusion
      proteins of disparate regions of the FimH molecule with an affinity tag MalE, and
      tested each of the fusion products in vitro for functional activity. The minimum
      region responsible for binding mouse bladder epithelial cells and a soluble
      mannoprotein, horseradish peroxidase, was contained within residues 1-100 of the
      FimH molecule. We validated and extended these findings by demonstrating that
      antibodies directed at the putative binding region of FimH or at synthetic
      peptides corresponding to epitopes within the binding domain could specifically
      block type 1 fimbriae-mediated bacterial adherence to bladder epithelial cells in
      situ and yeast cells in vitro. Next, we compared the ability of mice passively
      immunized intraperitoneally with antisera raised against residues 1-25 and 253
      264 of FimH or 1-13 of FimA to resist bladder colonization in vivo after
      intravesicular challenge with type 1-fimbriated E. coli. Only the antibody
      directed at the putative binding region of FimH (anti- s-FimH1-25) significantly
      reduced E. coli bladder infections in the experimental mouse model of urinary
      tract infections. Similar results were obtained when the mice were actively
      immunized with synthetic peptides corresponding to residues 1-25 and 253-264 of
      FimH or 1-13 of FimA. The mechanism of protection was attributed, at least in
      part, to inhibition of bacterial adherence to the bladder surface by s-FimH1-25
      specific antibody molecules that had filtered through the kidneys into the urine.
      The level of FimH antibodies entering the bladder from the circulatory system of
      the immunized mice was found to be markedly enhanced upon bacterial challenge.
      The potential broad spectrum activity of the protective FimH antibody was
      indicated from its serologic cross-reactivity with various urinary tract
      bacterial isolates bearing type 1 fimbriae. These findings could be relevant in
      the design of an efficacious and broadly reactive FimH vaccine against urinary
      tract infections.

PMID- 9276731
TI  - Lack of high affinity fiber receptor activity explains the resistance of ciliated
      airway epithelia to adenovirus infection.
AB  - Although recombinant adenoviruses are attractive vectors for gene transfer to
      airway epithelia, they have proven to be relatively inefficient. To investigate
      the mechanisms of adenovirus-mediated gene transfer to airway epithelia, we
      examined the role of adenovirus fiber and penton base, the two proteins involved
      in attachment to and entry of virus into the cell. We used human airway epithelia
      grown under conditions that allow differentiation and development of a ciliated
      apical surface that closely resembles the in vivo condition. We found that
      addition of fiber protein inhibited virus binding and vector-mediated gene
      transfer to immature airway epithelia, as well as to primary cultures of rat
      hepatocytes and HeLa cells. However, fiber protein had no effect on vector
      binding and gene transfer to ciliated airway epithelia. We obtained similar
      results with addition of penton base protein: the protein inhibited gene transfer
      to immature epithelia, whereas there was no effect with ciliated epithelia.
      Moreover, infection was not attenuated with an adenovirus containing a mutation
      in penton base that prevents the interaction with cell surface integrins. These
      data suggest that the receptors required for efficient infection by adenovirus
      are either not present or not available on the apical surface of ciliated human
      airway epithelia. The results explain the reason for inefficient gene transfer
      and suggest approaches for improvement.

PMID- 9276732
TI  - Modulation of eicosanoid metabolism in endothelial cells in a xenograft model.
      Role of cyclooxygenase-2.
AB  - Lipid inflammatory mediators are thought to play a critical role in the
      pathogenesis of vascular injury. Among the events which might cause the synthesis
      of eicosanoids in blood vessels is activation of the complement. To evaluate how
      complement might influence eicosanoid metabolism, we investigated endothelial
      cells exposed to xenoreactive antibodies and complement, as might occur in
      rejecting xenografts where severe vascular injury is a typical feature. While
      resting porcine aortic endothelial cells released only prostaglandin (PG) I2,
      endothelial cells stimulated with xenoreactive antibodies and complement released
      PGE2 and thromboxane A2 (TXA2), in addition to increased amounts of PGI2. This
      alteration in eicosanoid metabolism was associated with induction of
      cyclooxygenase (Cox)-2 and thromboxane synthase, but not Cox-1. Unlike results
      seen in other systems, the upregulation of Cox-2 and the subsequent release of
      eicosanoids by endothelial cells was not directly induced by complement but
      rather required production of IL-1alpha, which acted on endothelial cells as an
      autocrine factor. Since eicosanoids have a potent effect on inflammation,
      vascular tone and platelet aggregation, we postulated that the abnormalities in
      eicosanoid release induced by xenoreactive antibodies and complement might
      provide one explanation for the vascular injury, focal ischemia, and thrombosis
      observed in acute vascular rejection and other vasculitides mediated by
      complement.

PMID- 9276733
TI  - Biologically inactive growth hormone caused by an amino acid substitution.
AB  - Short stature caused by biologically inactive growth hormone (GH) is
      characterized by lack of GH action despite high immunoassayable GH levels in
      serum and marked catch-up growth to exogenous GH administration. We found a
      heterozygous single-base substitution (A-->G) in exon 4 of the GH-1 gene of a
      girl with short stature, clinically suspected to indicate the presence of
      bioinactive GH and resulting in the substitution of glycine for aspartic acid at
      codon 112. We confirmed the presence of mutant GH in the serum using isoelectric
      focusing analysis. The locus of mutation D112G was found within site 2 of the GH
      molecule in binding with GH receptor (GHR)/GH binding protein (GHBP). The
      expressed recombinant mutant GH tended to form a 1:1 instead of the 1:2 GH-GHBP
      complex normally produced by wild-type GH. The formation of a 1:2 GH-GHBP complex
      is compatible with the dimerization of GHRs by GH, a crucial step in GH signal
      transduction. Mutant GH was less potent than wild-type GH not only in
      phosphorylation of tyrosine residues in GHR, janus kinase 2 (JAK2), and signal
      transducers and activators of transcription 5 (STAT5) in IM-9 cells, but also in
      metabolic responses of BaF/GM cells, a stable clone transfected with cDNA of the
      chimera of the extracellular domain of human GHR, the transmembrane and the
      cytoplasmic domain of the human thrombopoietin receptor. These results indicate
      that the D112G mutation in the GH-1 gene causes production of bioinactive GH,
      which prevents dimerization of GHR and is therefore responsible for the patient's
      short stature.

PMID- 9276734
TI  - Leptin constrains acetylcholine-induced insulin secretion from pancreatic islets
      of ob/ob mice.
AB  - Hypersecretion of insulin from the pancreas is among the earliest detectable
      metabolic alterations in some genetically obese animals including the ob/ob mouse
      and in some obesity-prone humans. Since the primary cause of obesity in the ob/ob
      mouse is a lack of leptin due to a mutation in the ob gene, we tested the
      hypothesis that leptin targets a regulatory pathway in pancreatic islets to
      prevent hypersecretion of insulin. Insulin secretion is regulated by changes in
      blood glucose, as well as by peptides from the gastrointestinal tract and
      neurotransmitters that activate the pancreatic islet adenylyl cyclase (e.g.,
      glucagon-like peptide-1) and phospholipase C (PLC) (e.g., acetylcholine)
      signaling pathways to further potentiate glucose-induced insulin secretion.
      Effects of leptin on each of these regulatory pathways were thus examined. Leptin
      did not influence glucose or glucagon-like peptide-1-induced insulin secretion
      from islets of either ob/ob or lean mice, consistent with earlier findings that
      these regulatory pathways do not contribute to the early-onset hypersecretion of
      insulin from islets of ob/ob mice. However, leptin did constrain the enhanced PLC
      mediated insulin secretion characteristic of islets from ob/ob mice, without
      influencing release from islets of lean mice. A specific enhancement in PLC
      mediated insulin secretion is the earliest reported developmental alteration in
      insulin secretion from islets of ob/ob mice, and thus a logical target for leptin
      action. This action of leptin on PLC-mediated insulin secretion was dose
      dependent, rapid-onset (i.e., within 3 min), and reversible. Leptin was equally
      effective in constraining the enhanced insulin release from islets of ob/ob mice
      caused by protein kinase C (PKC) activation, a downstream mediator of the PLC
      signal pathway. One function of leptin in control of body composition is thus to
      target a PKC-regulated component of the PLC-PKC signaling system within islets to
      prevent hypersecretion of insulin.

PMID- 9276736
TI  - Low concentrations of nitric oxide increase oxygen affinity of sickle
      erythrocytes in vitro and in vivo.
AB  - The hallmark of sickle cell disease (SCD) is the polymerization of deoxygenated
      sickle hemoglobin (HbS). In SCD patients, one strategy to reduce red blood cell
      (RBC) sickling is to increase HbS oxygen affinity. Our objective was to determine
      if low concentrations of nitric oxide (NO) gas would augment the oxygen affinity
      of RBCs containing homozygous HbS (SS). Blood containing normal adult hemoglobin
      (AA) or SS RBCs was incubated in vitro in the presence of varying concentrations
      of NO up to 80 ppm, and oxygen dissociation curves (ODCs) were measured. In
      addition, blood was obtained from three AA and nine SS volunteers, before and
      after breathing 80 ppm NO in air for 45 min, and the ODCs were measured. Exposure
      of SS RBCs to 80 ppm NO in vitro for 5 min or longer decreased the partial
      pressure of oxygen at which hemoglobin is 50% saturated with oxygen (P50), an
      average of 15% (4.8+/-1.7 mmHg mean+/-SE; P < 0.001). The increase in SS RBC
      oxygen affinity correlated with the NO concentration. The P50 of AA RBCs was
      unchanged (P > 0.1) by 80 ppm NO. In SS volunteers breathing 80 ppm NO for 45
      min, the P50 decreased (P < 0.001) by 4.6+/-2.0 mmHg. 60 min after NO breathing
      was discontinued, the RBC P50 remained decreased in five of seven volunteers in
      whom the ODC was measured. There was no RBC P50 change (P > 0.1) in AA volunteers
      breathing NO. Methemoglobin (Mhb) remained low in all subjects breathing NO (SS
      Mhb 1.4+/-0.5%), and there was no correlation (r = 0.02) between the reduction in
      P50 and the change in Mhb. Thus, low concentrations of NO augment the oxygen
      affinity of sickle erythrocytes in vitro and in vivo without significant Mhb
      production. These results suggest that low concentrations of NO gas may offer an
      attractive new therapeutic model for the treatment of SCD.

PMID- 9276735
TI  - Stimulus coupling to transcription versus secretion in pheochromocytoma cells.
      Convergent and divergent signal transduction pathways and the crucial roles for
      route of cytosolic calcium entry and protein kinase C.
AB  - How do chromaffin cell secretory stimuli program resynthesis of secreted peptides
      and amines? We previously showed that the physiologic nicotinic cholinergic
      signal for secretion also activates the biosynthesis of chromogranin A, the major
      protein released with catecholamines. Here, we examine signal transduction
      pathways whereby secretory stimuli influence exocytotic secretion versus
      chromogranin A transcription. Both secretion and transcription depended on
      initial nicotinic-triggered sodium entry into the cytosol, followed by calcium
      entry through -type voltage-gated channels. When calcium entered through -type
      channels, activation of secretion paralleled activation of transcription (r =
      0.897, P = 0.002). Calcium entry from intracellular stores or through calcium
      ionophore channels activated secretion, though not transcription. Nicotinic
      stimulated transcription depended upon protein kinase C activation; nicotine
      caused translocation of protein kinase C to the cell membrane fraction, and
      inhibition of protein kinase C blocked activation of transcription, while
      activation of protein kinase C mimicked nicotine effects. Transcriptional
      responses to both nicotine and protein kinase C mapped principally onto the
      chromogranin A promoter's cAMP response element (TGACGTAA; CRE box). KCREB, a
      dominant negative mutant of the CRE-binding protein CREB, blunted activation of
      chromogranin A transcription by nicotine, phorbol ester, or membrane
      depolarization. We conclude that activation of chromogranin A transcription by
      secretory stimulation in chromaffin cells is highly dependent upon precise route
      of calcium entry into the cytosol; transcription occurred after entry of calcium
      through -type channels on the cell surface, and was mediated by protein kinase C
      activation. The trans-acting factor CREB ultimately relays the secretory signal
      to the chromogranin A promoter's CRE box in cis.

PMID- 9276737
TI  - The role of the B7 costimulatory pathway in experimental cold
      ischemia/reperfusion injury.
AB  - Ischemia/reperfusion injury associated with organ retrieval and storage
      influences the development of chronic graft dysfunction, the major clinical
      problem in solid organ transplantation. The potential role of mononuclear cells
      (T cells and monocyte/macrophages) in this type of injury is unknown. Inbred male
      Lewis rats were uninephrectomized and the left kidney perfused in situ with 10 ml
      of iced University of Wisconsin solution. Immunohistological studies showed
      mononuclear cell infiltration of the ischemic organs associated with the
      upregulation of MHC class II antigen expression. Reverse transcriptase-PCR
      indicated that T cell associated cytokines and monocyte/macrophage activation
      markers/products are upregulated early after the ischemic insult. B7 expression
      occurred within 24 h and peaked at 3 d. Plasma creatinine levels rose transiently
      with complete recovery of renal function by 5 d. Animals began to develop
      progressive proteinuria after 8-12 wk, indicative of the long-term functional
      consequences of early ischemia/reperfusion injury. Blockade of T cell CD28-B7
      costimulation with CTLA4Ig resulted in significant inhibition of T cell and
      macrophage infiltration and activation in situ. Treated animals did not exhibit
      transient renal dysfunction, nor developed proteinuria over time. This is the
      first demonstration that blocking T cell costimulatory activation in the absence
      of alloantigen can prevent the early and late consequences of
      ischemia/reperfusion injury.

PMID- 9276738
TI  - Expression of mucosal homing receptor alpha4beta7 by circulating CD4+ cells with
      memory for intestinal rotavirus.
AB  - The integrin alpha4beta7 mediates lymphocyte binding to mucosal addressin cell
      adhesion molecule-1, and its expression defines lymphocytes capable of
      trafficking through the intestines and the intestinal lymphoid tissues. We
      examined the ability of discrete alpha4beta7(hi) and alpha4beta7- subsets of
      circulating memory phenotype (CD45RA-) CD4+ T cells to proliferate in response to
      rotavirus, a ubiquitous intestinal pathogen. alpha4beta7(hi) memory (CD45RA-)
      CD4+ T cells displayed much greater reactivity to rotavirus than alpha4beta7-
      memory or naive (CD45RA+) CD4+ T cells. In contrast, alpha4beta7- memory cells
      were the predominant population responsive to mumps antigen after intramuscular
      vaccination. Our results are consistent with the conclusion that natural
      rotavirus infection, an enteric pathogen, results in a specific circulating
      memory CD4+ response that is largely limited to the gut-homing alpha4beta7+
      subpopulation. This phenotype is not shared with memory cells elicited by
      intramuscular immunization (shown here) or by skin contact allergens. The results
      support the hypothesis that gut trafficking memory CD4+ T cells comprise cellular
      memory for intestinal antigens and suggest that regulated expression of
      alpha4beta7 helps target and segregate intestinal versus systemic immune
      response.

PMID- 9276739
TI  - Induction of heme oxygenase-1 inhibits the monocyte transmigration induced by
      mildly oxidized LDL.
AB  - Heme catabolic processes produce the antioxidants biliverdin and bilirubin, as
      well as the potent prooxidant free iron. Since these products have opposing
      effects on oxidative stress, it is not clear whether heme catabolism promotes or
      inhibits inflammatory processes, including atherosclerotic lesion formation. Heme
      oxygenase (HO) catalyzes the rate-limiting step of heme catabolism. We used
      cocultures of human aortic endothelial cells and smooth muscle cells to examine
      the possible role of HO in early atherosclerosis. Heme oxygenase-1 (HO-1), the
      inducible isoform of HO, was highly induced by mildly oxidized LDL, and augmented
      induction was observed with hemin pretreatment. This augmented HO-1 induction
      resulted in the reduction of monocyte chemotaxis in response to LDL oxidation.
      Conversely, inhibition of HO by a specific inhibitor, Sn-protoporphyrin IX,
      enhanced chemotaxis. Furthermore, pretreatment with biliverdin or bilirubin, the
      products of HO, reduced chemotaxis. Oxidized phospholipids in the mildly oxidized
      LDL appear to be responsible for HO-1 induction, since oxidized but not native
      arachidonic acid-containing phospholipids also induced HO-1. These results
      suggest that HO-1 induced by mildly oxidized LDL may protect against the
      induction of inflammatory responses in artery wall cells through the production
      of the antioxidants biliverdin and bilirubin.

PMID- 9276740
TI  - Growth as a solid tumor or reduced glucose concentrations in culture reversibly
      induce CD44-mediated hyaluronan recognition by Chinese hamster ovary cells.
AB  - The density, molecular isoform, and posttranslational modifications of CD44 can
      markedly influence growth and metastatic behavior of tumors. Many CD44 functions,
      including some involving tumors, have been attributed to its ability to recognize
      hyaluronan (HA). However, only certain CD44-bearing cells bind soluble or
      immobilized HA. We now show that CD44 made by wild-type Chinese hamster ovary
      (CHO-K1) cells and a ligand-binding subclone differ with respect to N-linked
      glycosylation. While both bear CD44 with highly branched, complex-type
      glycoforms, CD44 expressed by the wild type was more extensively sialylated. CHO
      K1 cells which failed to recognize HA when grown in culture gained this ability
      when grown as a solid tumor and reverted to a non-HA-binding state when returned
      to culture. The ability of CHO-K1 cells to recognize HA was also reversibly
      induced when glucose concentrations in the medium were reduced. Glucose
      restriction influenced CD44-mediated HA binding by many but not all, of a series
      of murine tumors. Glucose concentrations and glycosylation inhibitors only
      partially influenced CD44 receptor function on resting murine B lymphocytes.
      These observations suggest that glucose levels or other local environmental
      conditions may markedly influence glycosylation pathways used by some tumor
      cells, resulting in dramatic alteration of CD44-mediated functions.

PMID- 9276741
TI  - Elevated circulating free fatty acid levels impair endothelium-dependent
      vasodilation.
AB  - We have recently shown that insulin-resistant obese subjects exhibit impaired
      endothelial function. Here, we test the hypothesis that elevation of circulating
      FFA to levels seen in insulin-resistant subjects can impair endothelial function.
      We studied leg blood flow responses to graded intrafemoral artery infusions of
      the endothelium-dependent vasodilator methacholine chloride (Mch) or the
      endothelium-independent vasodilator sodium nitroprusside during the infusion of
      saline and after raising systemic circulating FFA levels exogenously via a low-
      or high-dose infusion of Intralipid plus heparin or endogenously by an infusion
      of somatostatin (SRIF) to produce insulinopenia in groups of lean healthy humans.
      After 2 h of infusion of Intralipid plus heparin, FFA levels increased from 562+/
      95 to 1,303+/-188 micromol, and from 350+/-35 to 3,850+/-371 micromol (P < 0.001)
      vs. saline for both low- and high-dose groups, respectively. Mch-induced
      vasodilation relative to baseline was reduced by approximately 20% in response to
      the raised FFA levels in both groups (P < 0.05, saline vs. FFA, ANOVA). In
      contrast, similar FFA elevation did not change leg blood flow responses to sodium
      nitroprusside. During the 2-h SRIF infusion, insulin levels fell, and FFA levels
      rose from 474+/-22 to 1,042+/-116 micromol (P < 0.01); Mch-induced vasodilation
      was reduced by approximately 20% (P < 0.02, saline vs. SRIF, ANOVA). Replacement
      of basal insulin levels during SRIF resulted in a fall of FFA levels from 545+/
      47 to 228+/-61 micromol, and prevented the impairment of Mch-induced vasodilation
      seen with SRIF alone. In conclusion, (a) elevated circulating FFA levels cause
      endothelial dysfunction, and (b) impaired endothelial function in insulin
      resistant humans may be secondary to the elevated FFA concentrations observed in
      these patients.

PMID- 9276742
TI  - Identification of an obesity quantitative trait locus on mouse chromosome 2 and
      evidence of linkage to body fat and insulin on the human homologous region 20q.
AB  - Chromosomal synteny between the mouse model and humans was used to map a gene for
      the complex trait of obesity. Analysis of NZB/BINJ x SM/J intercross mice located
      a quantitative trait locus (QTL) for obesity on distal mouse chromosome 2, in a
      region syntenic with a large region of human chromosome 20, showing linkage to
      percent body fat (likelihood of the odds [LOD] score 3.6) and fat mass (LOD score
      4.3). The QTL was confirmed in a congenic mouse strain. To test whether the QTL
      contributes to human obesity, we studied linkage between markers located within a
      52-cM region extending from 20p12 to 20q13.3 and measures of obesity in 650
      French Canadian subjects from 152 pedigrees participating in the Quebec Family
      Study. Sib-pair analysis based on a maximum of 258 sib pairs revealed suggestive
      linkages between the percentage of body fat (P < 0.004), body mass index (P <
      0.008), and fasting insulin (P < 0.0005) and a locus extending approximately from
      ADA (the adenosine deaminase gene) to MC3R (the melanocortin 3 receptor gene).
      These data provide evidence that a locus on human chromosome 20q contributes to
      body fat and insulin in a human population, and demonstrate the utility of using
      interspecies syntenic relationships to find relevant disease loci in humans.

PMID- 9276743
TI  - Melanoma cells constitutively release an anchor-positive soluble form of
      protectin (sCD59) that retains functional activities in homologous complement
      mediated cytotoxicity.
AB  - Protectin (CD59), a glycosylphosphatidylinositol-anchored cell membrane
      glycoprotein, is differentially expressed on melanocytic cells and represents the
      main restriction factor of C-mediated lysis of melanoma cells. In this study, we
      report that CD59-positive melanoma cells constitutively release a soluble form of
      CD59 (sCD59), and that its levels directly correlate (r = 0.926; P < 0.05) with
      the amount of membrane-bound CD59. SDS-PAGE analysis showed that the molecular
      components of sCD59 are similar to those of cellular CD59 expressed by melanoma
      cells. Melanoma-released sCD59 is anchor positive since it inserts into cell
      membranes of homologous cells that transiently increase their expression of CD59.
      Moreover, sCD59 is functional: it blocks the binding of the anti-CD59 mAb YTH53.1
      to melanoma cells and reverses its effects on C-mediated lysis. In fact,
      preincubation of mAb YTH53.1 with scalar doses of conditioned media of CD59
      positive but not of CD59-negative melanoma cells reduced significantly (P <
      0.05), and in a dose-dependent fashion, the enhancement of C-mediated lysis of
      anti-GD3-sensitized melanoma cells induced by the masking of cellular CD59 by mAb
      YTH53.1. Altogether, these data demonstrate that CD59-positive human melanoma
      cells release a soluble form of CD59 that is structurally similar to cellular
      CD59, retains its anchoring ability, is functional, and may impair the
      effectiveness of clinical approaches to humoral immunotherapy for human melanoma.

PMID- 9276744
TI  - A major role for neutrophils in experimental bullous pemphigoid.
AB  - Bullous pemphigoid (BP) is an inflammatory subepidermal blistering disease
      associated with an IgG autoimmune response to the hemidesmosomal protein, BP180.
      Using a passive transfer mouse model, our group has shown previously that
      antibodies to the murine BP180 (mBP180) ectodomain are capable of triggering a
      blistering skin disease that closely mimics human BP. In this study, we
      investigated the role of neutrophils in the immunopathogenesis of this disease
      model. BALB/c mice depleted of circulating neutrophils by treatment with
      neutrophil-specific antibodies were no longer susceptible to the pathogenic
      effects of anti-mBP180 IgG. IgG and complement were deposited at the dermal
      epidermal junction of these animals, but there was no evidence of inflammatory
      infiltration or blistering. C5-deficient mice, which are resistant to the
      pathogenic activity of anti-mBP180 IgG, could be made susceptible to this IgG
      mediated blistering disease by intradermal administration of a neutrophil
      chemoattractant, IL-8 or C5a. Intraperitoneal injection of IL-8, which sequesters
      neutrophils in the peritoneal cavity, interferes with anti-mBP180-induced
      neutrophilic infiltration of the skin and prevented the development of BP disease
      in BALB/c mice. These findings provide the first direct evidence that neutrophils
      recruited to the skin via a C5-dependent pathway play an essential role in
      subepidermal blister formation in experimental BP, and suggest new directions for
      disease intervention.

PMID- 9276745
TI  - Eicosanoid excretion in hepatic cirrhosis. Predominance of 20-HETE.
AB  - The cytochrome P450 system transforms AA to hydroxyeicosatetraenoic acid (HETE)
      metabolites that are vasoactive and affect transport in several nephron segments.
      A principal product of this system, 20-HETE, participates in key mechanisms that
      regulate the renal circulation and extracellular fluid volume. We hypothesized
      that excess production of 20-HETE, which constricts the renal vasculature,
      contributes to the renal functional disturbances in patients with hepatic
      cirrhosis, particularly the depression of renal hemodynamics. The development of
      a precise and sensitive gas chromatographic/mass spectrometric method makes it
      possible to measure 20-HETE and the subterminal HETEs (16-,17-,18-, and 19-HETEs)
      in biological fluids. As 20-HETE was excreted as the glucuronide conjugate,
      measurement of 20-HETE required treatment of urine with glucuronidase. We
      measured HETEs in the urine of patients with cirrhosis, and compared these values
      to those of normal subjects. Urinary excretion rate of 20-HETE was highest in
      patients with ascites; 12.5+/-3.2 ng/min vs. 5.0+/-1.5 and 1.6+/-0.2 ng/min in
      cirrhotic patients without ascites and in normal subjects, respectively.
      Excretion of 16-, 17-, and 18-HETEs was not increased. In patients with
      cirrhosis, the excretory rate of 20-HETE was several-fold higher than those of
      prostaglandins and thromboxane, whereas in normal subjects 20-HETE and
      prostaglandins were excreted at similar rates. Of the eicosanoids, only increased
      excretion of 20-HETE in subjects with cirrhosis was correlated (r = -0.61; P <
      0.01) with reduction of renal plasma flow (RPF).

PMID- 9276746
TI  - Heparin-binding ligands mediate autocrine epidermal growth factor receptor
      activation In skin organ culture.
AB  - Exogenous EGF and TGF-alpha accelerate wound healing, but treatment effects are
      often modest. Using short-term human skin organ culture, we found that autocrine
      EGF receptor activation could account for this observation. Amphiregulin and
      heparin-binding EGF-like growth factor (HB-EGF) transcripts were rapidly and
      markedly induced, whereas EGF and TGF-alpha mRNAs were undetectable or only
      slightly increased. Vascular permeability factor and keratin 6 transcripts were
      also strongly induced, albeit with a >/= 3 h delay relative to HB-EGF and
      amphiregulin. All four transcripts were upregulated in actual healing skin
      wounds, HB-EGF and keratin 6 being the most prominent. The highly EGF receptor
      specific tyrosine kinase inhibitor PD153035 strongly inhibited induction of all
      four transcripts in organ culture, as well as release of immunoreactive HB-EGF
      into the medium. These effects were confirmed using the anti-EGF receptor mAb 225
      IgG. Neither PD153035 nor 225 IgG was toxic to keratinocytes, as judged by
      calcein-AM uptake. PD153035 completely abrogated the proliferative phase of
      keratinocyte outgrowth in skin explant cultures, whereas it had no effect on the
      antecedent migratory phase. Based on these results, we conclude that EGF receptor
      activation by highly inducible, keratinocyte-derived heparin-binding ligands is
      an important mechanism for amplification and transmission of the cutaneous wound
      healing signal.

PMID- 9276747
TI  - Taxol-resistant epithelial ovarian tumors are associated with altered expression
      of specific beta-tubulin isotypes.
AB  - The treatment of advanced ovarian cancer with taxol is hindered by the
      development of drug resistance. The cellular target for taxol is the microtubule
      that is stabilized by the drug. Taxol preferentially binds to the beta subunit of
      tubulin of which there are six distinct isotypes in mammalian cells. We have used
      highly specific oligonucleotides and polymerase chain reaction to analyze
      expression of all six beta-tubulin genes. Human lung cancer cells (A549) were
      selected in 12 and 24 nM taxol resulting in cell lines that were 9- and 17-fold
      resistant, respectively. These cells displayed an altered ratio of classes I, II,
      III, and IVa beta-tubulin isotypes. Ovarian tumors, seven untreated primary and
      four taxol- resistant tumor-bearing ascites, displayed significant increases (P <
      0.005) in classes I (3.6-fold), III (4.4-fold), and IVa (7.6-fold) isotypes in
      the taxol-resistant samples as compared with untreated primary ovarian tumors.
      The increased expression appears to be related to the resistance phenotype, as
      the basal levels of the class III and IVa isotypes in the untreated tumors were
      extremely low. This is the first report of altered expression of specific beta
      tubulin genes in taxol-resistant ovarian tumors and we propose that the latter
      may play a role in clinical resistance to taxol.

PMID- 9276748
TI  - Identification of a cis-acting regulatory element conferring inducibility of the
      atrial natriuretic factor gene in acute pressure overload.
AB  - To identify the cis-acting regulatory element(s) which control the induction of
      the atrial natriuretic factor (ANF) gene in acute pressure overload, DNA
      constructs consisting of promoter elements linked to a reporter gene were
      injected into the myocardium of dogs, which underwent aortic banding or were sham
      operated. Expression of a reporter gene construct harboring the ANF promoter (
      3400ANF) was induced 6-12-fold after 7 d of pressure overload. An internal
      deletion of 556 bp (nucleotide sequence -693 to -137) completely abrogated the
      inducibility of the ANF reporter gene construct. An activator protein-1 (AP1)
      like site (-496 to -489) and a cAMP regulatory element (CRE) (-602 to -596) are
      located within the deleted sequence. Site-directed mutagenesis of the AP1-like
      site but not the CRE completely prevented the induction of this construct to
      acute pressure overload. Further, the AP1-like site was able to confer
      inducibility of a heterologous promoter (beta-myosin heavy chain) to higher
      values than controls. Gel mobility shift assay (GMSA) supershift analysis was
      performed using a radiolabeled probe of the ANF promoter (-506/-483) that
      included the AP1-like site (ATGAATCA) sequence, as well as a probe converted to
      contain an AP1 consensus sequence (ATGACTCA). GMSA analysis demonstrated that the
      ANF AP1-like element could bind both a constitutively expressed factor and the
      AP1 proteins, and conversion to a true AP1 site increased its affinity for AP1.
      However, 7 d after the onset of pressure overload, the AP1 proteins were present
      only at low levels, and the major complex formed by the ANF AP1-like probe was
      not supershifted by a jun antibody. Using a large animal model of pressure
      overload, we have demonstrated that a unique cis-acting element was primarily
      responsible for the overload induction of the ANF gene.

PMID- 9276749
TI  - Hepatic gluconeogenic fluxes and glycogen turnover during fasting in humans. A
      stable isotope study.
AB  - Fluxes through intrahepatic glucose-producing metabolic pathways were measured in
      normal humans during overnight or prolonged (60 h) fasting. The glucuronate probe
      was used to measure the turnover and sources of hepatic UDP-glucose; mass
      isotopomer distribution analysis from [2-13C1]glycerol for gluconeogenesis and
      UDP-gluconeogenesis; [U-13C6]glucose for glucose production (GP) and the direct
      UDP-glucose pathway; and [1-2H1]galactose for UDP-glucose flux and retention in
      hepatic glycogen. After overnight fasting, GP (fluxes in milligram per kilogram
      per minute) was 2.19+/-0.09, of which 0.79 (36%) was from gluconeogenesis, 1.40
      was from glycogenolysis, 0.30 was retained in glycogen via UDP-gluconeogenesis,
      and 0.17 entered hepatic UDP-glucose by the direct pathway. Thus, total flux
      through the gluconeogenic pathway (1.09) represented 54% of extrahepatic glucose
      disposal (2.02) and the net hepatic glycogen depletion rate was 0.93 (46%).
      Prolonging [2-13C1]glycerol infusion slowly increased measured fractional
      gluconeogenesis. In response to prolonged fasting, GP was lower (1. 43+/-0.06)
      and fractional and absolute gluconeogenesis were higher (78+/-2% and 1.11+/-0.07,
      respectively). The small but nonzero glycogen input to plasma glucose (0.32+/
      0.03) was completely balanced by retained UDP-gluconeogenesis (0.31+/-0.02).
      Total gluconeogenic pathway flux therefore accounted for 99+/-2% of GP, but with
      a glycogen cycle interposed. Prolonging isotope infusion to 10 h increased
      measured fractional gluconeogenesis and UDP-gluconeogenesis to 84-96%, implying
      replacement of glycogen by gluconeogenic-labeled glucose. Moreover, after
      glucagon administration, GP (1.65), recovery of [1-2H1]galactose label in plasma
      glucose (25%) and fractional gluconeogenesis (91%) increased, such that 78%
      (0.45/0.59) of glycogen released was labeled (i.e., of recent gluconeogenic
      origin). In conclusion, hepatic gluconeogenic flux into glycogen and glycogen
      turnover persist during fasting in humans, reconciling inconsistencies in the
      literature and interposing another locus of control in the normal pathway of GP.

PMID- 9276750
TI  - Adrenaline stimulates glucagon secretion in pancreatic A-cells by increasing the
      Ca2+ current and the number of granules close to the L-type Ca2+ channels.
AB  - We have monitored electrical activity, voltage-gated Ca2+ currents, and
      exocytosis in single rat glucagon-secreting pancreatic A-cells. The A-cells were
      electrically excitable and generated spontaneous Na+- and Ca2+-dependent action
      potentials. Under basal conditions, exocytosis was tightly linked to Ca2+ influx
      through omega-conotoxin-GVIA-sensitive (N-type) Ca2+ channels. Stimulation of the
      A-cells with adrenaline (via beta-adrenergic receptors) or forskolin produced a
      greater than fourfold PKA-dependent potentiation of depolarization-evoked
      exocytosis. This enhancement of exocytosis was due to a 50% enhancement of Ca2+
      influx through L-type Ca2+ channels, an effect that accounted for <30% of the
      total stimulatory action. The remaining 70% of the stimulation was attributable
      to an acceleration of granule mobilization resulting in a fivefold increase in
      the number of readily releasable granules near the L-type Ca2+ channels.

PMID- 9276751
TI  - Probing the structure of the diphtheria toxin channel. Reactivity in planar lipid
      bilayer membranes of cysteine-substituted mutant channels with
      methanethiosulfonate derivatives.
AB  - Previous work has established that the 61 amino acid stretch from residue 322 to
      382 in the T-domain of diphtheria toxin forms channels indistinguishable in ion
      conducting properties from those formed by the entire T-domain. In the crystal
      structure of the toxin's water-soluble form, the bulk of this stretch is an alpha
      helical hairpin, designated TH8-9. The present study was directed at determining
      which residues in TH8-9 line the ion-conducting pathway of the channel; i.e., its
      lumen or entrances. To this end, we singly mutated 49 of TH8-9's 51 residues (328
      376) to cysteines, formed channels with the mutant T-domain proteins in planar
      lipid bilayers, and then determined whether they reacted with small, charged,
      lipid-insoluble, sulfhydryl-specific methanethiosulfonate (MTS) derivatives added
      to the bathing solutions. The indication of a reaction, and that the residue
      lined the ion-conducting pathway, was a sudden change in single-channel
      conductance and/or flickering behavior. The results of this study were surprising
      in two respects. First, of the 49 cysteine-substituted residues in TH8-9 tested,
      23 reacted with MTS derivatives in a most unusual pattern consisting of two
      segments: one extending from 329 to 341 (11 of 13 reacted), and the other from
      347 to 359 (12 of 13 reacted); none of the residues outside of these two segments
      appeared to react. Second, in every cysteine mutant channel manifesting an MTS
      effect, only one transition in single-channel conductance (or flickering
      behavior) occurred, not the several expected for a multimeric channel. Our
      results are not consistent with an alpha-helical or beta-strand model for the
      channel, but instead suggest an open, flexible structure. Moreover, contrary to
      common sense, they indicate that the channel is not multimeric but is formed from
      only one TH8-9 unit of the T-domain.

PMID- 9276752
TI  - Cyclic AMP levels, adenylyl cyclase activity, and their stimulation by serotonin
      quantified in intact neurons.
AB  - In molluscan central neurons that express cAMP-gated Na+ current (INa,cAMP),
      estimates of the cAMP binding affinity of the channels have suggested that
      effective native intracellular cAMP concentrations should be much higher than
      characteristic of most cells. Using neurons of the marine opisthobranch snail
      Pleurobranchaea californica, we applied theory and conventional voltage clamp
      techniques to use INa,cAMP to report basal levels of endogenous cAMP and adenylyl
      cyclase, and their stimulation by serotonin. Measurements were calibrated to
      iontophoretic cAMP injection currents to enable expression of the data in molar
      terms. In 30 neurons, serotonin stimulated on average a 23-fold increase in
      submembrane [cAMP], effected largely by an 18-fold increase in adenylyl cyclase
      activity. Serotonin stimulation of adenylyl cyclase and [cAMP] was inversely
      proportional to cells' resting adenylyl cyclase activity. Average cAMP
      concentration at the membrane rose from 3.6 to 27.6 microM, levels consistent
      with the expected cAMP dissociation constants of the INa,cAMP channels. These
      measures confirm the functional character of INa,cAMP in the context of high
      levels of native cAMP. Methods similar to those employed here might be used to
      establish critical characters of cyclic nucleotide metabolism in the many cells
      of invertebrates and vertebrates that are being found to express ion currents
      gated by direct binding of cyclic nucleotides.

PMID- 9276753
TI  - Allosteric gating of a large conductance Ca-activated K+ channel.
AB  - Large-conductance Ca-activated potassium channels (BK channels) are uniquely
      sensitive to both membrane potential and intracellular Ca2+. Recent work has
      demonstrated that in the gating of these channels there are voltage-sensitive
      steps that are separate from Ca2+ binding steps. Based on this result and the
      macroscopic steady state and kinetic properties of the cloned BK channel mslo, we
      have recently proposed a general kinetic scheme to describe the interaction
      between voltage and Ca2+ in the gating of the mslo channel (Cui, J., D.H. Cox,
      and R.W. Aldrich. 1997. J. Gen. Physiol. In press.). This scheme supposes that
      the channel exists in two main conformations, closed and open. The conformational
      change between closed and open is voltage dependent. Ca2+ binds to both the
      closed and open conformations, but on average binds more tightly to the open
      conformation and thereby promotes channel opening. Here we describe the basic
      properties of models of this form and test their ability to mimic mslo
      macroscopic steady state and kinetic behavior. The simplest form of this scheme
      corresponds to a voltage-dependent version of the Monod-Wyman-Changeux (MWC)
      model of allosteric proteins. The success of voltage-dependent MWC models in
      describing many aspects of mslo gating suggests that these channels may share a
      common molecular mechanism with other allosteric proteins whose behaviors have
      been modeled using the MWC formalism. We also demonstrate how this scheme can
      arise as a simplification of a more complex scheme that is based on the premise
      that the channel is a homotetramer with a single Ca2+ binding site and a single
      voltage sensor in each subunit. Aspects of the mslo data not well fitted by the
      simplified scheme will likely be better accounted for by this more general
      scheme. The kinetic schemes discussed in this paper may be useful in interpreting
      the effects of BK channel modifications or mutations.

PMID- 9276754
TI  - Plasma membrane water permeability of cultured cells and epithelia measured by
      light microscopy with spatial filtering.
AB  - A method was developed to measure the osmotic water permeability (Pf) of plasma
      membranes in cell layers and applied to cells and epithelia expressing molecular
      water channels. It was found that the integrated intensity of monochromatic light
      in a phase contrast or dark field microscope was dependent on relative cell
      volume. For cells of different size and shape (Sf9, MDCK, CHO, A549, tracheal
      epithelia, BHK), increased cell volume was associated with decreased signal
      intensity; generally the signal decreased 10-20% for a twofold increase in cell
      volume. A theory relating signal intensity to relative cell volume was developed
      based on spatial filtering and changes in optical path length associated with
      cell volume changes. Theory predictions were confirmed by signal measurements of
      cell layers bathed in solutions of various osmolarities and refractive indices.
      The excellent signal-to-noise ratio of the transmitted light detection permitted
      measurement of cell volume changes of <1%. The method was applied to characterize
      transfected cells and tissues that natively express water channels. Pf in control
      Chinese hamster ovary cells was low (0.0012 cm/s at 23 degrees C) and increased
      more than fourfold upon stable transfection with aquaporins 1, 2, 4, or 5. Pf in
      apical and basolateral membranes in polarized epithelial cells grown on porous
      supports was measured. Pfbl and Pfap were 0.0011 and 0.0024 cm/s (MDCK cells),
      and 0.0039 and 0.0052 cm/s (human tracheal cells) at 23 degrees C. In intact toad
      urinary bladder, basolateral Pf was 0.036 cm/s and apical membrane Pf after
      vasopressin stimulation was 0.025 cm/s at 23 degrees C. The results establish
      light microscopy with spatial filtering as a technically simple and quantitative
      method to measure water permeability in cell layers and provide the first
      measurement of the apical and basolateral membrane permeabilities of several
      important epithelial cell types.

PMID- 9276755
TI  - Swelling-activated Gd3+-sensitive cation current and cell volume regulation in
      rabbit ventricular myocytes.
AB  - The role of swelling-activated currents in cell volume regulation is unclear.
      Currents elicited by swelling rabbit ventricular myocytes in solutions with 0.6
      0.9x normal osmolarity were studied using amphotericin perforated patch clamp
      techniques, and cell volume was examined concurrently by digital video
      microscopy. Graded swelling caused graded activation of an inwardly rectifying,
      time-independent cation current (ICir,swell) that was reversibly blocked by Gd3+,
      but ICir,swell was not detected in isotonic or hypertonic media. This current was
      not related to IK1 because it was insensitive to Ba2+. The PK/PNa ratio for
      ICir,swell was 5.9 +/- 0.3, implying that inward current is largely Na+ under
      physiological conditions. Increasing bath K+ increased gCir,swell but decreased
      rectification. Gd3+ block was fitted with a K0.5 of 1.7 +/- 0.3 microM and Hill
      coefficient, n, of 1.7 +/- 0.4. Exposure to Gd3+ also reduced hypotonic swelling
      by up to approximately 30%, and block of current preceded the volume change by
      approximately 1 min. Gd3+-induced cell shrinkage was proportional to ICir,swell
      when ICir,swell was varied by graded swelling or Gd3+ concentration and was
      voltage dependent, reflecting the voltage dependence of ICir,swell. Integrating
      the blocked ion flux and calculating the resulting change in osmolarity suggested
      that ICir,swell was sufficient to explain the majority of the volume change at 
      80 mV. In addition, swelling activated an outwardly rectifying Cl- current,
      ICl,swell. This current was absent after Cl- replacement, reversed at ECl, and
      was blocked by 1 mM 9-anthracene carboxylic acid. Block of ICl,swell provoked a
      28% increase in swelling in hypotonic media. Thus, both cation and anion swelling
      activated currents modulated the volume of ventricular myocytes. Besides its
      effects on cell volume, ICir,swell is expected to cause diastolic depolarization.
      Activation of ICir, swell also is likely to affect contraction and other
      physiological processes in myocytes.

PMID- 9276756
TI  - Modulation of voltage-dependent properties of a swelling-activated Cl- current.
AB  - We used the patch-clamp technique to study the voltage-dependent properties of
      the swelling-activated Cl- current (ICl,swell) in BC3H1 myoblasts. This Cl-
      current is outwardly rectifying and exhibits time-dependent inactivation at
      positive potentials (potential for half-maximal inactivation of +75 mV). Single
      channel Cl- currents with similar voltage-dependent characteristics could be
      measured in outside-out patches pulled from swollen cells. The estimated single
      channel slope conductance in the region between +60 and +140 mV was 47 pS. The
      time course of inactivation was well described by a double exponential function,
      with a voltage-independent fast time constant (approximately 60 ms) and a voltage
      dependent slow time constant (>200 ms). Recovery from inactivation, which
      occurred over the physiological voltage range, was also well described by a
      double exponential function, with a voltage-dependent fast time constant (10-80
      ms) and a voltage-dependent slow time constant (>100 ms). The inactivation
      process was significantly accelerated by reducing the pH, increasing the Mg2+
      concentration or reducing the Cl- concentration of the extracellular solution.
      Replacing extracellular Cl- by other permeant anions shifted the inactivation
      curve in parallel with their relative permeabilities (SCN- > I- > NO3- > Cl- >>
      gluconate). A leftward shift of the inactivation curve could also be induced by
      channel blockers. Additionally, the permeant anion and the channel blockers, but
      not external pH or Mg2+, modulated the recovery from inactivation. In conclusion,
      our results show that the voltage-dependent properties of ICl,swell are strongly
      influenced by external pH, external divalent cations, and by the nature of the
      permeant anion.

PMID- 9276757
TI  - Activation of Na+-permeant cation channel by stretch and cyclic AMP-dependent
      phosphorylation in renal epithelial A6 cells.
AB  - It is currently believed that a nonselective cation (NSC) channel, which responds
      to arginine vasotocin (an antidiuretic hormone) and stretch, regulates Na+
      absorption in the distal nephron. However, the mechanisms of regulation of this
      channel remain incompletely characterized. To study the mechanisms of regulation
      of this channel, we used renal epithelial cells (A6) cultured on permeable
      supports. The apical membrane of confluent monolayers of A6 cells expressed a 29
      pS channel, which was activated by stretch or by 3-isobutyl-1-methylxanthine
      (IBMX), an inhibitor of phosphodiesterase. This channel had an identical
      selectivity for Na+, K+, Li+, and Cs+, but little selectivity for Ca2+ (PCa/PNa <
      0.005) or Cl- (PCl/PNa < 0.01), identifying it as an NSC channel. Stretch had no
      additional effects on the open probability (Po) of the IBMX-activated channel.
      This channel had one open ("O") and two closed (short "CS" and long "CL") states
      under basal, stretch-, or IBMX-stimulated conditions. Both stretch and IBMX
      increased the Po of the channel without any detectable changes in the mean open
      or closed times. These observations led us to the conclusion that a kinetic model
      "CL <--> CS <--> O" was the most suitable among three possible linear models.
      According to this model, IBMX or stretch would decrease the leaving rate of the
      channel for CL from CS, resulting in an increase in Po. Cytochalasin D
      pretreatment abolished the response to stretch or IBMX without altering the basal
      activity. H89 (an inhibitor of cAMP-dependent protein kinase) completely
      abolished the response to both stretch and IBMX, but, unlike cytochalasin D, also
      diminished the basal activity. We conclude that: (a) the functional properties of
      the cAMP-activated NSC channel are similar to those of the stretch-activated one,
      (b) the actin cytoskeleton plays a crucial role in the activation of the NSC
      channel induced by stretch and cAMP, and (c) the basal activity of the NSC
      channel is maintained by PKA-dependent phosphorylation but is not dependent on
      actin microfilaments.

PMID- 9276758
TI  - Microfilament dynamics during cell movement and chemotaxis monitored using a GFP
      actin fusion protein.
AB  - BACKGROUND: The microfilament system in the cortex of highly motile cells, such
      as neutrophils and cells of the eukaryotic microorganism Dictyostelium
      discoideum, is subject to rapid re-organization, both spontaneously and in
      response to external signals. In particular, actin polymerization induced by a
      gradient of chemoattractant leads to local accumulation of filamentous actin and
      protrusion of a 'leading edge' of the cell in the direction of the gradient. In
      order to study the dynamics of actin in these processes, actin was tagged at its
      amino terminus with green fluorescent protein (GFP) and observed with
      fluorescence microscopy in living cells of D. discoideum. RESULTS: Purified GFP
      actin was capable of copolymerizing with actin. In the transfected cells of D.
      discoideum studied, GFP-actin made up 10-20% of the total actin. Microfilaments
      containing GFP-actin were capable of generating force with myosin in an in vitro
      assay. Observations of single living cells using fluorescence microscopy showed
      that the fusion protein was enriched in cell projections, including filopodia and
      leading edges, and that the fusion protein reflected the dynamics of the
      microfilament system in cells that were freely moving, being chemotactically
      stimulated, or aggregated. When confocal sections of fixed cells containing GFP
      actin were labeled with fluorescent phalloidin, which binds only to filamentous
      actin, there was a correlation between the areas of GFP-actin and phalloidin
      fluorescence, but there were distinct sites in which GFP-actin was more
      prominent. CONCLUSIONS: Double labeling with GFP-actin and other probes provides
      an indication of the various states of actin in motile cells. A major portion of
      the actin assemblies visualized using GFP-actin are networks or bundles of
      filamentous actin. Other clusters of GFP-actin might represent stores of
      monomeric actin in the form of complexes with actin-sequestering proteins.

PMID- 9276759
TI  - Coronin and vacuolin identify consecutive stages of a late, actin-coated
      endocytic compartment in Dictyostelium.
AB  - Cells of the unicellular eukaryote Dictyostelium discoideum take up all their
      nutrients by endocytosis. Both particle- and fluid-containing vacuoles are
      transiently surrounded by a cytoskeletal coat [1] [2]. When this coat has
      dissociated, acidification and digestion of the vesicle contents occur, followed
      by exocytosis of the indigestible remnants after 60-90 minutes. At least nine
      compartments are needed for mathematical modelling of endocytic transit [3],
      suggesting that markers associate for only a few minutes with a specific
      endocytic compartment. Among the proteins that have been identified as components
      of endocytic vesicles are actin, subunits of the V-H+ ATPase and small GTP
      binding proteins of the Rab family [4] [5] [6] [7]. Using a monoclonal antibody
      produced against Dictyostelium endocytic vesicles, we have isolated a cDNA
      corresponding to a novel protein that we have named vacuolin. In order to
      determine the precise step along the endocytic pathway that involves vacuolin, we
      generated a fusion protein of the green fluorescent protein (GFP) and vacuolin.
      GFP-vacuolin-decorated vesicles were identified as a post-lysosomal compartment
      that acquires endocytic markers shortly before exocytosis. At earlier stages,
      this post-lysosomal compartment was identified by the binding of a tagged
      cytoskeletal protein, coronin-GFP. Vacuoles were coated with filamentous actin
      along the entire post-lysosomal pathway, and the integrity of the actin coat was
      required for exocytosis.

PMID- 9276760
TI  - Autologous versus allogeneic T cell-stimulated IL-6 production by dermal
      fibroblasts.
AB  - T cells adhere to human dermal fibroblasts (HDF). This cellular interaction leads
      to a pronounced secretion of the proinflammatory cytokines IL-6 and IL-8 via a
      juxtacrine stimulation induced by HDF-associated IL-1. Upon stimulation,
      fibroblasts express various surface proteins such as MCH-I molecules, which may
      interact with corresponding receptors on T cells. The present study was conducted
      to further investigate the mechanism of this complex interaction with regard to
      the secretion of IL-6 in cocultures of T cells and HDF. IL-6 was time- and dose
      dependently upregulated in such cocultures. Spatial separation of the cells by
      microporous membranes resulted in a 90% reduction of IL-6 secretion, but when
      cells had limited cell contact IL-6 secretion was increased again. Allogeneic
      cocultures of T cells and HDF showed increased capacity of IL-6 stimulation as
      compared to autologous cultures. Our results suggest that MHC-I/T cell receptor
      interaction modulates IL-6 secretion in allogeneic and autologous cocultures.

PMID- 9276761
TI  - Peritoneal lavage reduces lipopolysaccharide-induced elevation of serum TNF-alpha
      and IL-6 mortality in mice.
AB  - The contribution of peritoneal cells to lipopolysaccharide (LPS)-induced
      elevation of serum TNF-alpha and IL-6 levels and mortality has been studied.
      Peritoneal lavage performed before LPS administration reduced serum cytokine
      levels by approximately 50% and mortality from 50 to 100%. The effect of
      peritoneal lavage is due to the removal of peritoneal cells as reinjection of
      peritoneal cells eliminated the protective effect of lavage on LPS-induced
      mortality. A special role of peritoneal macrophages in the systemic response to
      LPS was suggested by the finding that LPS-induced an increase in intracellular
      TNF-alpha and IL-6 peritoneal macrophages but in neither splenic nor bone marrow
      macrophages. Intraperitoneal injection of thioglycollate broth 4 days prior to
      lavage increased the number of peritoneal cells removed by lavage and increased
      protection from LPS mortality. Peritoneal lavage performed 30 to 120 minutes
      after the LPS administration completely protected all mice from LPS-induced
      mortality, suggesting the possibility that such treatment may offer a novel
      therapeutic approach to septic shock.

PMID- 9276762
TI  - Rifamycins inhibit human neutrophil functions: new derivatives with potential
      antiinflammatory activity.
AB  - In our study we investigated the effect of rifamycin SV, rifamycin B, rifampicin
      and five semisynthetic derivatives on human neutrophil functions such as
      locomotion, superoxide production and degranulation stimulated by specific
      agonists. All compounds were tested at concentrations ranging from 10(-9) to 10(
      5) M. Among the newly synthesized compounds the most active we found to be the
      derivatives carrying an acidic substituent at C3: these significantly lowered the
      superoxide generation induced by PMA throughout the entire concentration range,
      whereas rifamycin SV, rifamycin B and rifampicin were effective only at the
      highest concentrations. Moreover, chemotactic movement was significantly
      attenuated by derivative R4, rifamycin B and rifamycin SV at high doses; granule
      enzyme release was unaffected by all compounds.

PMID- 9276763
TI  - The pulmonary inflammatory response to experimental fecal peritonitis: relative
      roles of tumor necrosis factor-alpha and endotoxin.
AB  - The roles of endotoxin (LPS) and tumor necrosis factor-alpha (TNF-alpha) in the
      causation of organ injury during sepsis are unclear. To study LPS and TNF-alpha
      in the genesis of lung inflammation after cecal ligation and puncture (CLP), we
      used endotoxin-resistant (C3H/HeJ) and endotoxin-sensitive mice (C3H/HeOuJ). We
      examined lung neutrophil sequestration, interleukin 1 (IL-1)beta mRNA expression,
      IL-1 beta protein expression, and injury. We also determined the expression of
      two C-X-C chemokine mRNAs, macrophage inflammatory protein-2 (MIP-2) and KC, in
      the lung to determine whether in vivo, endotoxin, or TNF-alpha are significant
      modulators of MIP-2 and KC mRNA expression. After CLP, increased neutrophils
      sequestrated in the lungs of both strains of mice and coincided with an increase
      in expression of IL-1 beta, MIP-2 and KC mRNAs, and IL-1 beta protein. Lung and
      serum TNF-alpha were significantly increased in the C3H/HeOuJ strain but not in
      the C3H/HeJ strain. Histologic studies of the lung revealed similar injury in
      both strains. Our results suggest that bacterial factors other than endotoxin
      cause lung neutrophil sequestration and injury after CLP and, further, that TNF
      alpha production is not a prerequisite. Our findings also suggest a potential
      role for local pulmonary chemokine production in the control of neutrophil
      sequestration after CLP.

PMID- 9276764
TI  - Prostaglandin E2 is the major arachidonic acid metabolite secreted by esophageal
      mucosal cells in rabbits.
AB  - Unlike gastric mucosa, it has been considered that lipoxygenase metabolites
      protect the esophageal mucosa and that prostaglandins are only secreted in the
      presence of esophageal inflammation. The aim of this study was to determine the
      profile of arachidonic acid metabolites and their response to regulatory
      compounds in rabbit esophageal mucosal cells in culture. Eicosanoids secreted
      into the medium were extracted and identified by HPLC and RIA. Esophageal mucosal
      cells in culture metabolized arachidonic acid mainly through the cycloxygenase
      pathway and PGE2 was the major arachidonic acid metabolite secreted. The addition
      of IL-1 beta and A23187 (calcium ionophore) stimulated PGE2 synthesis. In basal
      conditions neither leukotrienes nor HETEs were detected. However, the addition of
      the NDGA induced the secretion of lipoxygenase metabolites identified as 12-15
      HETEs. In conclusion, rabbit esophageal epithelial cells in culture metabolize
      arachidonic acid via both cycloxygenase and lipoxygenase pathways. In our system,
      PGE2 was the main arachidonic acid metabolite.

PMID- 9276765
TI  - Effect of topically applied cyclooxygenase-2-selective inhibitors on arachidonic
      acid- and tetradecanoylphorbol acetate-induced dermal inflammation in the mouse.
AB  - The topical effects of cyclooxygenase-2 (COX-2)-selective inhibitors, flosulide
      (CGP 28238), L-745,337 and SC-57,666 were examined in AA- and TPA-induced ear
      dermal inflammation in the mouse. The doses that caused 50% inhibition in AA
      edema (ED50) were 2.4, 0.45 and 0.35 mg/ear for flosulide, L-745,337 and SC
      57,666, respectively. The respective ED50s in TPA-edema were 1, 0.45 and 0.14.
      Indomethacin and zileuton showed higher activity than the COX-2-selective
      inhibitors in both models. Flosulide and L-745,337 inhibited the AA-induced
      increase in 6-keto-PGF1 alpha, while SC-57,666 was inactive, 80% inhibition was
      seen with indomethacin while zileuton had no effect. COX-2-selective inhibitors
      and indomethacin had no effect on LTB4 levels, while zileuton produced a 50%
      inhibition. The TPA-induced increase in 6-keto-PGF1 alpha was greatly inhibited
      by all COX-2 inhibitors while LTB4 was potentiated by both flosulide and L
      745,337. Indomethacin inhibited 6-keto-PGF1 alpha and zileuton reduced 6-keto-PGF
      alpha and strongly reduced LTB4. The neutrophil influx induced by AA was lower
      than that of TPA. Myeloperoxidase (MPO) levels were lowered by flosulide and L
      745,337 but not by SC-57,666. TPA-induced MPO increase was decreased by all COX-2
      inhibitors. Indomethacin and zileuton had similar effect on AA and TPA-induced
      increase in MPO. The results indicate that COX-2-selective inhibitors showed
      lower topical anti-inflammatory activity than indomethacin or zileuton.

PMID- 9276766
TI  - Role of endogenous and exogenous nitric oxide on intestinal mucosa and microflora
      in the rat.
AB  - In the present study the effects of exogenous and endogenous nitric oxide (NO) on
      intestinal bacteria and on the intestinal tissue integrity have been investigated
      in healthy rats and in rats receiving bacterial endotoxin (LPS). A segment of
      jejunum was taken in order to evaluate tissue damage and hematoxylin-eosin
      staining; microbiological studies were carried out collecting stool samples.
      Administration of LPS (5 mg kg-1 i.v.) induced a moderate jejunal damage, which
      was completely prevented by NG-nitro-L-arginine methyl ester (L-NAME), 5 mg kg-1
      s.c.), thus suggesting a damage of endogenous NO on the intestinal mucosa; sodium
      nitroprusside (SNP, 10 mg kg-1 os) reduced significantly jejunal damage induced
      by LPS. Endogenous NO produced by the administration of LPS resulted to be
      cytotoxic for all examined aerobic and anaerobic bacteria, while exogenous NO,
      released from SNP, showed an inhibitory effect only on Entero. faecalis and E.
      coli growth. From our data, it seems reasonable to conclude that high local
      levels of NO are required in order to observe jejunal damage and cytotoxic
      effects on aerobic and anaerobic faecal flora.

PMID- 9276767
TI  - Modulation of nitric oxide synthase activity by ibuprofen.
AB  - Inhibition of NO synthesis represents a new therapeutical approach in the
      treatment of inflammation. Clinical use of NOS inhibitors will necessitate the
      design of drugs selective for iNOS, because inhibition of constitutive
      endothelial NOS may cause adverse cardiovascular side effects. This study
      examines the effect of ibuprofen and its stereoeisomeric components on the
      activation of iNOS and cNOS as well as on the NO production by human umbilical
      vein endothelial cells. At therapeutic concentrations Ibuprofen activated iNOS
      and inhibited NOS. In endothelial cell culture experiments activation of NO
      production was seen especially at supratherapeutic ibuprofen concentrations. Both
      stereoisomeric components of ibuprofen showed comparable effects. This drug can
      therefore not be used for the selective inhibition of iNOS.

PMID- 9276768
TI  - Rapid cardiac growth--mechanical, neural and endocrine dependence.
AB  - Rapid growth of the cardiac left ventricle is a hallmark of the neonatal period.
      During the first 2 weeks of life in the piglet, weight of the left ventricle
      increases 4 fold. The increase in weight is accompanied by approximately a 4 fold
      increase in myocyte volume indicating hypertrophic growth. Total RNA also
      increases approximately 4 fold indicating that the mechanism of growth involves
      greater ribosome content and greater capacity for protein synthesis. The rapid
      rate of ribosome formation and protein synthesis cannot be further accelerated in
      isolated perfused hearts by insulin, agents that increase 3',5'-cyclic
      monophosphate, alpha 1-adrenergic agonists or angiotensin II. In an attempt to
      slow cardiac growth and make it responsive to growth-promoting agonists, piglets
      are treated with an angiotensin converting enzyme inhibitor, enalapril maleate.
      Enalapril decreases left ventricular growth by 19% and total RNA content by 36%.
      When enalapril-treated hearts are perfused in vitro for 1 h, alpha 1-adrenergic
      agents restore rates of ribosome formation to control values but angiotensin II
      has no effect. In left ventricular myocytes that are cultured for 3 days, an
      alpha 1-adrenergic agonist and endothelin increases the rate of protein synthesis
      by 20 to 75% but angiotensin II has only a marginal effect (8%). These findings
      indicate that inhibition of growth by enalapril most likely is due to decreased
      ventricular pressure development that is secondary to peripheral vasodilation and
      a fall in mean arterial pressure.

PMID- 9276769
TI  - Exercise-induced T-wave alternans as a marker of high risk in patients with
      hypertrophic cardiomyopathy.
AB  - Microvolt-level T-wave alternans (alternating morphology from beat to beat)
      during atrial pacing and exercise may predict ventricular tachycardia (VT) and
      fibrillation (VF) in ischemic heart disease. We tested whether such alternans
      during exercise could identify high-risk patients with hypertrophic
      cardiomyopathy (HCM). We studied 14 HCM patients and 9 normal control subjects
      for T-wave alternans u sing the CH2000 system with 7 multisegment electrodes in a
      Frank orthogonal (XYZ) configuration. Bicycle ergometer exercise was used to
      increase the heart rate (HR) to 95-110 beats/min. Seven patients were at high
      risk for ventricular arrhythmias (1 with sustained VT, 3 with abnormal paced
      ventricular electrograms as seen in VF survivors, and 3 with nonsustained VT
      and/or an adverse family history), and the other 7 were at low risk. T-wave
      alternans was present if alternans > 1.9 microV was consistently present with the
      HR in excess of a patient-specific HR threshold. Alternans was found in 5 of 7
      high-risk patients (71%) vs none of 7 low-risk patients or 9 control subjects (p
      < 0.025 and p < 0.01, respectively). Notably, all 4 patients with sustained VT or
      abnormal ventricular electrograms showed alternans. Thus, high-risk patients with
      HCM often show T-wave alternans. Microvolt-level alternans during exercise may be
      a useful marker for ventricular arrhythmic risk in patients with HCM.

PMID- 9276770
TI  - Soluble tumor necrosis factor receptors are elevated in relation to severity of
      congestive heart failure.
AB  - The level of tumor necrosis factor alpha (TNF-alpha) is increased in patients
      with congestive heart failure and may play an important role in the development
      and progression of heart failure. Two types of TNF receptor (TNF-RI and TNF-RII)
      are expressed in virtually every cell and have different biologic roles. Soluble
      forms of the two receptors (sTNF-RI and sTNF-RII) have been identified as
      extracellular domain fragments. Serum levels of TNF-alpha, sTNF-RI and sTNF-RII
      were measured in 66 patients with heart failure and 27 control subjects using an
      enzyme-linked immunosorbent assay (ELISA). Hemodynamic variables, norepinephrine,
      atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) were
      evaluated. TNF-alpha was significantly higher in patients with heart failure than
      in controls subjects (9.4 +/- 1.4 vs 4.8 +/- 0.8 pg/ml; p < 0.05). sTNF-RI and 
      RII were significantly increased in relation to the severity of heart failure
      (control subjects, 0.66 +/- 0.04 and 1.97 +/- 0.15 ng/ml; NYHA class II, 1.10 +/-
      0.08 and 2.28 +/- 0.12 ng/ml; NYHA class III, 1.63 +/- 0.22 and 3.00 +/- 0.24
      ng/ml; NYHA class IV, 2.78 +/- 0.46 and 4.52 +/- 0.62 ng/ml, respectively). In 9
      patients whose clinical symptoms improved after treatment, the levels of sTNF-RI
      and -RII decreased by 17.3 +/- 5.7% (p < 0.05) and 22.1 +/- 6.9% (p < 0.05),
      respectively. There were significant positive correlations between sTNF-RI and 
      RII and mean pulmonary pressure (r = 0.69 and r = 0.61; p < 0.001) and mean
      capillary wedge pressure (r = 0.65 and r = 0.54; p < 0.001 and p < 0.01,
      respectively), but not with left ventricular end-diastolic volume or ejection
      fraction (NS). sTNF-RI and -RII were also significantly positively correlated
      with plasma levels of norepinephrine (r = 0.75 and r = 0.50; p < 0.001 and p <
      0.05), ANP (r = 0.72 and r = 0.70; p < 0.001), and BNP (r = 0.60 and r = 0.60; p
      < 0.001). In conclusion, soluble TNF receptors are increased in proportion to the
      severity of congestive heart failure and may reflect the current status of
      congestive heart failure rather than the level of left ventricular dysfunction.

PMID- 9276771
TI  - Correlations between resting regional wall motion and regional myocardial blood
      flow (at rest and during exercise) in infarct-related myocardium--a study with
      [13N]ammonia positron emission tomography.
AB  - We evaluated quantitatively the correlations between resting wall motion and
      regional myocardial blood flow (RMBF; at rest and during exercise) in infarct
      related myocardium. The study was performed in 28 subjects: 21 patients who had
      previously suffered myocardial infarction of the anteroseptal wall, and 7 normal
      individuals. Positron emission tomography (PET) with [13N]ammonia was performed
      at rest and during low-grade exercise (bicycle ergometer fixed at 25 W for 6.5
      min), and RMBF was measured quantitatively from the radioactivity in myocardial
      tissue and arterial blood. Resting regional wall motion was calculated using the
      centerline method on left ventriculographic findings. Resting regional wall
      motion was correlated with RMBF both at rest and during exercise in the infarct
      areas (anterior walls; y = 2.74 +/- 4.25 x 10(-2)x, r = 0.43, at rest; and y = 
      2.48 + 3.04 x 10(-2)x, r = 0.48, during exercise, p < 0.05; septal walls; y = 
      3.61 + 5.64 x 10(-2)x, r = 0.62, at rest; and y = -3.46 + 4.31 x 10(-2)x, r =
      0.62, during exercise, p < 0.01). In each infarct-related wall, the coefficient
      (the slope) during exercise was smaller than that at rest (3.04 vs 4.25 and 4.31
      vs 5.64 in each), and the infarct areas with preserved wall motion showed higher
      RMBF during exercise than those with reduced wall motion. Our results may show
      that wall motion depends on viable but ischemic myocardium in infarct-related
      walls.

PMID- 9276772
TI  - Incidence of ischemic strokes in hypertrophic cardiomyopathy is markedly
      increased if complicated by atrial fibrillation.
AB  - The clinical outcome and the incidence of ischemic strokes in patients with
      hypertrophic cardiomyopathy (HCM) with and without atrial fibrillation (AF) were
      examined. Eighty-three patients with HCM, complicated by AF in 19 patients, and
      131 patients with AF but without HCM were studied retrospectively. Primary
      endpoints (ischemic strokes or cardiac death, whichever occurred first) and
      ischemic strokes were examined by Kaplan-Meier curves. In the patients with HCM,
      the primary endpoints occurred more frequently in those with AF than in those
      without AF (event rate at 5 year 23.0% vs 12.3%, p < 0.01). Similarly, the
      frequency of ischemic strokes in HCM was also much higher with AF than without AF
      (23.0% vs 5.9% at 5 years, p < 0.01). According to multivariate Cox analysis, the
      strong independent risk factor for ischemic strokes in HCM was AF (p < 0.01),
      whereas in patients with AF they were HCM (p < 0.01) and age (p < 0.01). These
      results suggest that incidence of ischemic strokes in HCM is markedly increased
      if complicated by AF as compared with that in patients with AF alone.

PMID- 9276773
TI  - The CryoLife-O'Brien composite stentless porcine aortic xenograft valve in 118
      patients.
AB  - The CryoLife-O'Brien stentless valve is a composite trileaflet porcine aortic
      valve. It is assembled from 3 non-coronary leaflets and has no foreign material
      support. It is therefore truly stentless. From December 1992 to January 1996, 118
      patients with aortic valve replacement had a CryoLife-O'Brien stentless valve
      inserted at the Prince Charles Hospital, Brisbane. The mean age was 73 years
      (range 59-89) and 54% were men. Most patients had aortic stenosis secondary to a
      calcific degenerative valve. Follow-up is 100% with hematological and
      echocardiographic studies before discharge, at 6 months, and at 12-18 months.
      Five deaths (2 early and 3 late) have occurred and morbidity includes 3 strokes,
      1 peripheral embolism, 3 perivalvular leaks, and 1 patient with late
      endocarditis. Valve performance has been good, with low transvalvular gradients
      and only a trace or no regurgitation in over 95% of patients after 18 months. No
      structural deterioration or hemolysis has occurred. Echocardiographic
      surveillance confirms a very effective central orifice. Short-term results show
      that the overall performance of the CryoLife-O'Brien stentless valve has been
      very satisfactory, with low mortality and morbidity in this elderly group of
      patients. The benefits include the absence of prosthetic material, wide leaflet
      coaptation, and a quick and easy insertion. Long-term anticoagulation is not
      necessary. It is particularly suitable for elderly patients with a symmetrical
      aortic root.

PMID- 9276775
TI  - Transcatheter neodymium-yttrium-aluminum-garnet laser coagulation of canine
      ventricle using a balloon-tipped cardioscope.
AB  - The feasibility of transcatheter laser ablation of the canine left ventricle (LV)
      was tested using a newly developed cardioscope. In 17 anesthetized dogs, a
      combined laser-endoscope catheter, consisting of an endoscope encased in a 7
      French flexible catheter with an inflatable and transparent balloon at the distal
      end, was introduced into the LV via the carotid artery. A 1064-nm neodymium
      yttrium-aluminum-garnet (Nd:YAG) laser was delivered by laser optic fiber, which
      was introduced through the transport channel and positioned inside the saline
      filled balloon. In 16 of 17 dogs, the endocardial surface of the LV was clearly
      observed. Laser energy totaling 500-5,000 J was applied sequentially in 13 dogs
      and laser irradiation was completed in all but 2 of the dogs. The excised hearts
      revealed well-demarcated oval-shaped lesions 2.5-9.5 mm deep in 7 of 11 dogs.
      Histologic sections revealed coagulation necrosis surrounded by a rim of
      contraction band necrosis. Thus, transballoon laser photocoagulation of the
      beating LV is feasible. The newly combined laser-endoscope catheter, which is
      still in its preliminary stages and needs to be improved to increase the success
      rate of photocoagulation, appears to be a promising alternative modality for
      catheter ablative therapy for ventricular tachycardia.

PMID- 9276774
TI  - Protective effect of the angiotensin-converting enzyme inhibitor captopril on
      postischemic myocardial damage in perfused rat heart.
AB  - This study was undertaken to examine whether a sulfhydryl-containing angiotensin
      converting enzyme (ACE) inhibitor, captopril, improves postischemic cardiac
      function and myocardial metabolism in the perfused working rat heart, and to
      elucidate the mechanism by which captopril protects the myocardium from
      postischemic damage. Isolated rat hearts were perfused by the working heart
      technique for 15 min. Ischemia was then induced for 30 min by lowering the
      afterload pressure and coronary flow to zero. After ischemia, hearts were
      reperfused for 30 min by returning afterload pressure to 60 mmHg. Captopril, a
      non-sulfhydryl-containing ACE inhibitor, enalapril, or a type 1 angiotensin II
      receptor antagonist, DuP 753, was added to the perfusate 5 min before ischemia,
      and the treatment was continued during the first 10-min period of reperfusion. In
      all groups there was no significant difference in pressure-rate product, coronary
      flow, tissue levels of ATP, total adenine nucleotides (TANs), energy charge
      potential (ECP), or creatine phosphate (CrP) before and during ischemia. During
      reperfusion following ischemia, captopril significantly improved the recovery of
      pressure-rate product, coronary flow, and tissue levels of ATP, TAN, ECP, and
      CrP, but neither enalapril nor DuP 753 had an effect. In conclusion, captopril
      improved postischemic cardiac function and myocardial metabolism in the perfused
      rate heart and its effect was independent of the blunting of angiotensin II
      formation.

PMID- 9276776
TI  - Effect of intraluminal pressure on the intimal thickening in injured rabbit
      carotid arteries in an organ-culture system.
AB  - We developed an organ culture system in order to examine the effect of
      intraluminal pressure on intimal thickening in injured arteries. After
      endothelial denudation, an excised rabbit common carotid artery was incubated at
      37 degrees C in a glass bottle perfused with Dulbecco's modified Eagle medium
      containing 10% fetal calf serum at a constant flow rate of 6 ml/h at various
      static pressure of 60, 95, 130, 165, or 200 cmH2O. Intimal thickening, which
      consisted of smooth muscle cells and extracellular matrix, increased in a time-
      and pressure-dependent manner up to 130 cmH2O. Excessive pressured (165 and 200
      cmH2O), however, caused necrosis in the media. These results suggest that a rise
      in intraluminal pressure accelerates intimal thickening in injured arteries.

PMID- 9276778
TI  - Heparin and exercise treatment in a patient with arteriosclerosis obliterans.
AB  - A 65-year-old man was admitted with a diagnosis of arteriosclerosis obliterans.
      He had a 3-month history of intermittent claudication of the right leg. Physical
      examination revealed absence of pulsation of the right posterior tibial artery.
      Contrast angiography of lower extremities showed several obstructive lesions
      below the right popliteal artery. As interventional and surgical approached were
      not indicated, the patient was treated with exercise with heparin pretreatment
      (5,000 IU). As a result, walk distance on a floor was increased from 400 m to
      2,000 m, and repeat magnetic resonance angiography revealed increased flow to the
      right lower extremity. Thus, he was successfully treated with exercise and
      heparin pretreatment without any side effects.

PMID- 9276779
TI  - A large right coronary artery-left ventricle fistula with mild volume overload on
      the left ventricle owing to its capacitive action--pulsed Doppler and
      cineangiographic analyses in a patient.
AB  - A 54-year-old woman was admitted to our hospital because of a heart murmur
      without subjective symptoms. Angiography disclosed an enlarged right coronary
      artery and flow drainage into the left ventricle, ie, a large right coronary
      artery-left ventricle fistula. Analysis of pulsed Doppler studies and
      cineangiograms indicated considerable capacitance of this fistula owing to
      Windkessel action, which attenuated volume overload on the left ventricle. The
      features in this case suggest that evaluation of fistula hemodynamics is
      important in determining the overload on the ventricle through the fistula.

PMID- 9276777
TI  - Inhibitory effects of glibenclamide and pertussis toxin on the attenuation of
      ischemia-induced myocardial acidosis following ischemic preconditioning in dogs.
AB  - Ischemic preconditioning is known to be mediated by several humoral factors, such
      as adenosine, norepinephrine, and bradykinin. We examined intracellular signal
      transduction of ischemic preconditioning following receptor stimulation.
      Alterations in the pH of the ischemic bed were monitored to assess the response
      of control and ischemic-preconditioned myocardium to glibenclamide and pertussis
      toxin. Pentobarbital-anesthetized open-chest dogs were subjected to 40 min of
      ligation of the left anterior descending coronary artery. Ischemic
      preconditioning was elicited by 25-min periods of coronary ligation followed by 5
      min of reperfusion before a 40-min period of ligation. Glibenclamide (0.3
      mg/kg)was given i.v. 20 min before the onset of ischemic preconditioning.
      Pertussis toxin (6-10 micrograms/kg) was given i.v. 3 days before the experiment.
      Tissue myocardial pH was measured by a glass micro-pH electrode. Ischemia for 5
      min decreased myocardial pH and reperfusion returned it to the preischemic
      levels. Ischemia for 40 min decreased the myocardial pH from 7.43 +/- 0.06 to
      6.43 +/- 0.08. Ischemic preconditioning significantly attenuated the decrease in
      myocardial pH (6.57 +/- 0.06) induced by 40 min of ischemia. Pretreatment with
      either glibenclamide or pertussis toxin completely abolished the effect of
      ischemic preconditioning on ischemic myocardial acidosis. Ischemic
      preconditioning can attenuate ischemia-induced myocardial acidosis in dogs, and
      this effect is mediated by activation of adenosine triphosphate-sensitive
      potassium channels and pertussis toxin-sensitive guanosine triphosphate-binding
      protein.

PMID- 9276780
TI  - Lack of myocardial iodine-123 15-(p-iodiphenyl)-3-R,S-methylpentadecanoic acid
      (BMIPP) uptake and CD36 abnormality--CD36 deficiency and hypertrophic
      cardiomyopathy.

PMID- 9276781
TI  - Social expectancies and self-perceptions in anxiety-disordered children.
AB  - The link between anxiety and negative social expectancies was examined by
      comparing 47 anxiety-disordered children with 31 nonanxiety-disordered controls
      on social expectancies, social anxiety, and self-perceived social competence.
      Participants were exposed to a videotape of confederate children playing a game,
      being told the children were next door. In anticipation of joining the play,
      social expectations were assessed via thought-listing and a questionnaire.
      Parent, teacher, and child measures of sociability were completed prior to the
      experimental session. Results indicated that anxiety-disordered children reported
      significantly more negative social expectations, lower social self-competence,
      and higher levels of social anxiety than controls. Parents and teachers each
      rated the anxiety-disordered children as significantly more socially maladjusted
      than controls. Social anxiety was the best predictor of social expectancies.
      Given the importance of healthy peer relations, treatment implications for
      anxiety-disordered children are highlighted.

PMID- 9276782
TI  - Relaxation-induced EEG alterations in panic disorder patients.
AB  - Based on previous reports of relaxation-induced panic attacks in panic disorder
      patients, quantitative electroencephalographic (EEG) profiles and subjective
      anxiety ratings were assessed in panic disorder patients and normal controls
      listening to neutral and relaxation audiotapes. Regardless of tape condition,
      patients exhibited a greater frequency and severity of panic-related symptoms.
      Relaxation failed to alter panic-related symptom ratings or anxiety ratings in
      patients and controls. Theta and alpha increments were observed during
      relaxation, but only in normal controls. High frequency beta activity was less
      evident in patients, regardless of tape conditions. Results are discussed in
      relation to arousal and treatment issues in panic disorder.

PMID- 9276783
TI  - Lifetime comorbidity among anxiety disorders and between anxiety disorders and
      other mental disorders in adolescents.
AB  - We examine the lifetime comorbidity among anxiety disorders, and between anxiety
      disorders and other mental disorders, in a large (n = 1,507) community sample of
      high school students on whom extensive diagnostic data were available. Three
      diagnostic groups were formed: those with a lifetime anxiety disorder (n = 134);
      those with a nonanxiety disorder (n = 510); and those who had never met criteria
      for a mental disorder (n = 863). The intra-anxiety comorbidity rate was
      relatively low (18.7%), and was strongly associated with being female (92%). The
      lifetime comorbidity between anxiety and other mental disorders (primarily MDD)
      was substantial (73.1%) and was not associated with being female.

PMID- 9276784
TI  - Application of the Stages of Change Scale in a clinical drug trial.
AB  - The Stages of Change Scale (SOC: McConnaughy, Prochaska, & Velicer, 1983) was
      used to predict outcome among 131 outpatients with generalized anxiety disorder
      who were enrolled in a clinical drug trial. As predicted, subjects high on
      Precontemplation did not experience as much relief from anxiety as subjects low
      on Precontemplation, whereas subjects high on Contemplation or Action experienced
      more decrease in anxiety during the trial than subjects low on these stages.
      Contrary to our hypothesis, only Contemplation was related to illness severity
      changes, and scores on the Maintenance scale were not related to outcome. Of the
      four stage scores, only Maintenance was related to premature termination of
      treatment. There were no differences between drug (adinazolam) and placebo groups
      and only Action scores interacted with drug/placebo assignment in this study.
      Results suggest that the SOC may be useful in identifying individuals who are
      most likely to experience decreased anxiety while enrolled in a clinical drug
      trial.

PMID- 9276785
TI  - A neuro-evolutionary approach to the anxiety disorders.
AB  - BACKGROUND: Advances in our understanding of the anxiety disorders and in the
      application of evolutionary principles to medicine provide the possible basis for
      a neuro-evolutionary approach to these conditions. In this paper, initial steps
      taken towards such an approach are described. METHODS: Neuro-evolutionary
      accounts of each of the anxiety disorders have been offered. Notably, several of
      these accounts have suggested that particular anxiety disorders are mediated by
      specific brain-based false alarms. This paper reviews the strengths and
      weaknesses of such accounts. RESULTS: The false suffocation alarm of panic attack
      is the most fully elaborated of the neuro-evolutionary accounts of an anxiety
      disorder. However, viable neuro-evolutionary approaches have also been offered
      for other anxiety disorders, such as obsessive-compulsive disorder and social
      phobia. CONCLUSIONS: Further work is necessary to consolidate a neuro
      evolutionary approach to the anxiety disorders. Although the theoretical basis
      for such an approach has become increasingly appealing over the last several
      years, this foundation requires supplementation by further empirical research.

PMID- 9276786
TI  - Group and multifamily behavioral treatment for obsessive compulsive disorder: a
      pilot study.
AB  - Recent trends toward managed care in mental health settings require investigation
      of the efficacy and cost-effectiveness of treatments conducted over shorter time
      frames or with less therapist involvement. Findings are presented in an
      uncontrolled trial of two types of group behavioral treatments of OCD: group
      (GBT) and multifamily (MFBT). Seventeen patients (10 women and 7 men) diagnosed
      with OCD received a partially manualized GBT delivered by co-therapy teams in
      three groups of ten 2-hr sessions. Mean interview-based YBOCS scores reduced
      significantly at posttest and at 1-year follow-up, as did measures of overall
      functioning on the Sheehan Disability Scale at posttest and follow-up. A second
      cohort of 19 patients (14 women and 5 men) was treated with MFBT that included
      spouses/partners and parents in three co-therapy groups. Two groups received ten
      2-hr sessions and one received twelve 2-hr sessions. YBOCS scores reduced
      significantly at posttest and at 1-year follow-up, with corresponding gains in
      disability scores. Both group treatments showed large effects comparable to those
      reported for a more intensive individual behavioral treatment. Comparisons of
      treatments indicated that similar proportions of subjects were reliably changed
      at posttest and follow-up respectively, but more MFBT than GBT participants were
      clinically significantly improved. These promising cost effective group
      treatments remain to be tested in a controlled trial.

PMID- 9276787
TI  - Comparison of clinical characteristics in obsessive-compulsive disorder and body
      dysmorphic disorder.
AB  - Recent research has suggested that body dysmorphic disorder (BDD) is part of the
      spectrum of obsessive-compulsive disorders. In order to determine the extent of
      similarity for psychopathology measures, patients diagnosed with BDD were
      compared to a group of patients diagnosed with obsessive-compulsive disorder
      (OCD) on obsessionality, compulsivity, overvalued ideas, depression, and anxiety.
      Results indicate that BDD patients are similar to OCD patients for measures of
      obsessionality and compulsivity when BDD symptoms are assessed as such. BDD and
      OCD patients were also similar for measures of depression, and state and trait
      anxiety. OCD patients had higher levels of anxiety when measuring common physical
      symptoms associated with this affective reaction. BDD patients had higher levels
      of overvalued ideas, but fewer obsessive and compulsive symptoms. Overall, the
      results suggest that BDD is a variant of OCD, with special considerations given
      to degree of belief conviction (overvalued ideas.

PMID- 9276788
TI  - Presence in bovine milk of two protease inhibitors of the plasmin system.
AB  - Proteolysis, caused by the serine proteinase plasmin (EC 3.4.21.7) that is
      present in milk, influences the quality of dairy products. Within the plasmin
      system, activators and inhibitors control plasmin activity. This study
      investigated the presence in bovine milk of two serine proteinase inhibitors of
      the plasmin system, alpha(2)-antiplasmin and plasminogen activator inhibitor-1,
      and an isolation procedure used for partial purification of them from milk. Two
      colorimetric assays were used to detect either plasmin inhibitor activity or
      plasminogen activator inhibitor activity. Two inhibitors were partially purified
      from milk using a combination of ammonium sulfate fractionation and concanavalin
      A affinity chromatography. Plasminogen activator inhibitor-1 and alpha(2)
      antiplasmin antigens, which were associated with the inhibitory activities from
      bovine milk, were visualized by Western blot using commercial polyclonal
      antibodies raised against the corresponding human inhibitors. Both inhibitors
      were present in milk as several forms, possibly from the formation of complexes
      with other milk proteins. The predominant forms of the inhibitors in milk
      exhibited an approximate molecular mass of 60 kDa for alpha(2)-antiplasmin and 55
      kDa for plasminogen activator inhibitor-1.

PMID- 9276789
TI  - Purification and characterization of a dipeptidase from Lactobacillus casei ssp.
      casei IFPL 731 isolated from goat cheese made from raw milk.
AB  - A dipeptidase was purified to homogeneity from the cell-free extract of
      Lactobacillus casei ssp. casei IFPL 731 by a combination of heat treatment,
      hydrophobic interaction chromatography, anion-exchange chromatography, and gel
      filtration. A purification factor of 395-fold was obtained, and yield was 20%.
      The dipeptidase was shown to be a metal-dependent enzyme; optimal activity was at
      pH 7.5 and 60 to 75 degrees C, and the enzyme had a high degree of thermal
      stability. Molecular mass was estimated by SDS-PAGE and gel filtration to be 46
      kDa, which suggested that the enzyme existed as a monomer. Enzyme activity was
      most effectively inhibited by metal-chelating agents, reducing agents, or
      sulfhydryl group reagents. After inhibition with phenanthroline, activity was
      partially restored by Co2+ and Mn2+. The kinetics of Phe-Ala and Leu-Leu did not
      follow Michaelis-Menten saturation kinetics but exhibited a mixture of positive
      and negative cooperativity for the successive binding of molecules of the same
      substrate.

PMID- 9276791
TI  - Improvement of lactose digestion by humans following ingestion of unfermented
      acidophilus milk: influence of bile sensitivity, lactose transport, and acid
      tolerance of Lactobacillus acidophilus.
AB  - The influence of bile sensitivity, lactose transport, and acid tolerance of
      Lactobacillus acidophilus on in vivo digestion of lactose was investigated. Four
      strains of L. acidophilus exhibiting varied degrees of lactose transport, beta
      galactosidase activity, and bile sensitivity were used to prepare unfermented
      acidophilus milks. Lactose malabsorption was evaluated by measuring breath H2
      excretion off 11 lactose maldigesting subjects following ingestion of four
      acidophilus test milks. Test meals were fed in a randomized double-blind
      protocol. Consumption of acidophilus milk (2% fat) containing strains B, N1, and
      E significantly reduced mean total H2 production compared with that of the
      control reduced-fat (2% fat) milk, but milk containing strain ATCC 4356 did not
      differ from the control. Acidophilus milk containing L. acidophilus N1 was the
      most effective of the four acidophilus milks in improving lactose digestion and
      tolerance. Strain N1 exhibited the lowest beta-galactosidase activity and lactose
      transport but the greatest bile and acid tolerance of the four strains. The
      results indicated that bile and acid tolerance may be important factors to
      consider when L. acidophilus strains are selected for improving lactose digestion
      and tolerance.

PMID- 9276790
TI  - Expression of ropy and mucoid phenotypes in Lactococcus lactis.
AB  - Strains of Lactococcus lactis ssp. lactis and Lactococcus lactis ssp. cremoris
      were cultured under aerobic and anaerobic conditions on plates of whey agar,
      Elliker agar, and M17L agar at 15, 20, and 30 degrees C to determine the
      environmental conditions required for the expression of the ropy phenotype. Two
      strains, L. lactis ssp. cremoris Ropy 352 and L. lactis ssp. cremoris
      Hollandicus, exhibited two distinct polysaccharide phenotypes, ropy and mucoid.
      Expression of these phenotypes could be induced individually or simultaneously.
      The inducible nature of this response suggests that genetic regulators were
      present. Western blots were used to determine whether or not Lon protease and
      RcsA, two regulators of polysaccharide expression in Escherichia coli, were
      present in lactococci. Lon, a negative regulator, and RcsA, an unstable positive
      regulator, have been shown at the structural level to be conserved in a number of
      Gram-negative and Gram-positive microorganisms. The present study found evidence
      for structural conservation of Lon protease in lactococci. Less of the Lon-like
      protein was observed in the ropy strains than in the nonropy strains.

PMID- 9276792
TI  - Effect of storage temperatures and ingredients on growth of Bacillus cereus in
      coffee creamers.
AB  - Growth of Bacillus cereus ATCC 33018 was evaluated in half and half (10.5% fat),
      whipping cream (30% fat), and nondairy creamer (7.5% fat). Samples were
      inoculated with approximately 10 vegetative cells/ml or 100 spores/ml and were
      subsequently stored at 4, 7, 23 and 32 degrees C. Within 9 h at 32 degrees C and
      11 h at 23 degrees C, in both half and half and whipping cream, vegetative cells
      and spores reached population levels that can cause foodborne illness. No growth
      occurred in any product stored at 4 or 7 degrees C. Sodium stearoyl lactylate, a
      fatty acid derivative that is used as an emulsifier, inhibited growth of spores
      and vegetative cells in the nondairy creamers stored at either 32 or 23 degrees
      C.

PMID- 9276793
TI  - Monomer characterization and studies of self-association of the major beta-casein
      of human milk.
AB  - The casein form that has four organic phosphoryl groups, beta-casein (CN)-4P, is
      the major constituent (approximately 35%) of the beta-CN fraction of human milk
      and should play an important role in micelle structure and formation. In 3.3 M
      urea, the monomer is present with a molecular mass of 24,500 Da and a
      sedimentation coefficient of 1.3 S (Svedberg units, 10(-13)s). In 0.02 M NaCl and
      0.01 M imidazole (low salt buffer) at pH 7, the sedimentation coefficient was 1.5
      S, which increased to 14 S at 37 degrees C. Laser light scattering in low salt
      buffer and 9 mg/ml of protein indicated monomers with a radius of about 4 nm at 4
      degrees C. The size of the radius increased as temperature increased, and, at 37
      degrees C, the radius was about 12 nm. The molecular mass suggested the presence
      of about 47 monomers per polymer. In 0.25 M NaCl and with 10 nM Ca2+ prior to
      precipitation, the polymer attained a maximum radius of about 15 nm, which
      perhaps is the size of the smallest human milk micelles. The low value for
      reduced viscosity of 8.2 ml/g for the calcium-induced polymer was independent of
      protein concentration, suggesting a spherical shape and fixed size. Calcium
      apparently binds strongly to the phosphates; the dissociation constant was 8.1 x
      10(-4) M. Other constituents of milk, such as inorganic orthophosphate, may
      contribute to differences in the manner by which beta-CN, with various
      phosphorylation levels, participate in micelle formation.

PMID- 9276794
TI  - Milk plasmin during bovine mammary involution that has been accelerated by
      estrogen.
AB  - The purpose of this study was to evaluate whether the plasminogen and plasmin
      system within bovine mammary secretions was influenced by an estrogen treatment
      that was used to accelerate mammary tissue involution. Holstein cows were
      injected with 4 ml of ethanol excipient (n = 21) or 15 mg of estradiol-17 beta (n
      = 23) on each of the 4 d that preceded final milk removal. Dates of final milk
      removal (d 0) were designated as 60 d prior to expected dates of calving. Each
      mammary quarter was sampled once to collect secretions that corresponded to d 0,
      3, 11, and 25 or d 1, 7, 18, and 30 of the dry period. Concentrations of
      plasminogen, plasmin, and somatic cells in secretions increased earlier for
      treated cows than for control cows. The ratio of plasminogen to plasmin in
      secretions decreased earlier for treated cows than for control cows. These
      responses support the suggestion that the plasminogen and plasmin system is
      involved in the involution of bovine mammary tissue. Estrogen treatment increased
      the activation of plasminogen, which was evidenced by a precipitous decrease in
      the ratio of plasminogen to plasmin that occurred as concentrations of
      plasminogen and plasmin increased. The activation of plasminogen likely
      contributed to the increased rate of mammary tissue involution that was effected
      by exogenous estrogen. Endogenous estrogen secreted by the developing fetal and
      placental unit might mediate, in part, the gradual involution that occurs during
      lactation.

PMID- 9276795
TI  - Metabolic characteristics of induced ketosis in normal and obese dairy cows.
AB  - Four groups of 6 cows were used to determine the effects of body condition on
      induction of ketosis. At calving, obese cows were heavier by 108 kg and had a
      higher body condition score by 0.74 units than did normal cows. Susceptibility to
      induced ketosis was evaluated by restricting dry matter intake by 20% and feeding
      7% 1,3-butanediol from 15 to 49 d in milk (DIM) to one group of obese cows and to
      one group of normal cows. No normal or obese cows fed the control diet developed
      ketosis. Two normal and 2 obese cows developed ketonemia because of the induction
      protocol, and 1 cow in each of the two groups developed clinical ketosis. Obese
      cows lost 59% more body weight during the first 14 DIM than did normal cows, and
      cows fed the restricted diet plus 7% 1,3-butanediol lost 15% more body weight
      than did cows fed the control diet during the induction period. Concentrations of
      nonesterified fatty acids increased at parturition, peaked at 7 to 14 DIM, and
      returned to prepartum concentrations by 21 DIM. Plasma beta-hydroxybutyrate
      concentrations increased after calving and was increased additionally by the
      induction protocol. At the onset of lactation, plasma insulin decreased, plasma
      glucagon increased, hepatic triacylglycerols increased, and hepatic glycogen
      decreased. The incidence of ketonemia and clinical ketosis was the same for obese
      and normal cows, but, on the basis of changes of blood and liver composition,
      incidence of ketosis would probably increase if obese cows were overfed
      throughout the entire dry period.

PMID- 9276796
TI  - Effect of exogenous somatotropin on hematological variables of lactating cows and
      their offspring.
AB  - Eighty-two lactating Holstein cows in their first, second, or third lactation
      received either one, three, or five concurrent i.m. injections of a unit dose
      (0.6 g) of zinc methionyl bovine somatotropin (bST) or five doses of the vehicle.
      Injections were administered at 14-d intervals from 60 +/- 3 d postpartum until
      the end of lactation or until necropsy. Thirty-eight cows were continued on the
      treatment for a 2nd yr. Blood samples were collected at wk -2, -1, 3, and 7
      relative to the start of treatment and then every 8 wk (yr 1) or 4 wk (yr 2)
      thereafter. Untreated cows that were included in a survey of the resident herd
      were bled at wk 7 or 8, wk 10 or 11, and wk 13 or 14 of lactation and every 4 or
      8 wk thereafter. Calves were bled within 72 h of birth and at approximately 5 wk
      of age. Most parameters associated with erythrocytes were decreased mildly in
      cows that were treated with bST. However, data remained within generally accepted
      reference ranges, and changes were not of clinical importance. Decreased
      hematocrit was not associated with increased hemolysis, hemodilution, or clinical
      anemia. No morphological lesions related to treatment were noted in the bone
      marrow or spleen; bST did not affect the incidence of immature cell types. Energy
      and protein balances did not significantly affect the hematological results of
      the cows. Calves generally were unaffected by bST treatment of the dam, but
      heavier calves had higher parameters associated with erythrocyte and lymphocyte
      counts than did calves with lower body weight. Exogenous bST treatment caused
      predictable changes in hematological parameters of dairy cows.

PMID- 9276797
TI  - Estimation of interdependence among quarters of the bovine udder with subclinical
      mastitis and implications for analysis.
AB  - Interdependency among udder quarters with subclinical mastitis was evaluated on
      150 farms using a total of 35,828 udder quarters. The occurrence of high somatic
      cell count (SCC) (> 250,000 cells/ml) in 0, 3, and 4 quarters occurred at a
      higher rate than would be expected based on independence of the quarters. For all
      bacterial species, intramammary infection in 0, 2, 3, or 4 quarters of the same
      cow occurred at a higher rate than would be expected based on independence of the
      quarters. Intramammary infection and high SCC were found less often in front
      quarters than in rear quarters. High SCC and intramammary infection occurred more
      often in right front quarters than in left front quarters. High SCC in diagonal
      quarters occurred at a lower rate than expected. Corynebacterium bovis,
      Streptococcus agalactiae, and Staphylococcus aureus had the highest intraclass
      correlation within herd. Streptococcus uberis had a very low intraclass
      correlation within herd. The intraclass correlation within cow for the natural
      logarithm of SCC was 0.47. Corynebacterium bovis and Strep. agalactiae had the
      highest intraclass correlation within cow, and Streptococcus dysgalactiae had the
      lowest. Analytical methods were proposed to manage the problem of interdependence
      and its effect on the design or evaluation of field studies on subclinical
      mastitis.

PMID- 9276798
TI  - Bacteria counts in sawdust bedding.
AB  - Bacteria counts in untreated sawdust bedding were compared with those in sawdust
      bedding after the addition of lime and after daily replacement of bedding in the
      back one-third of the stalls. Addition of 1 kg of lime to 10 kg of sawdust
      reduced Gram-negative bacteria, coliforms, Klebsiella spp., and streptococci
      prior to use as bedding. Sawdust treated with lime also showed decreased bacteria
      counts compared with bacteria counts for sawdust that was replaced daily and
      compared with bacteria counts for control bedding after 1 d in the stall. The
      decrease in bacterial populations was related to an increase in bedding pH. Mean
      pH in the sawdust treated with lime was greater prior to use and after 1 d in the
      stall than the pH of other treatments. After 2 and 6 d in stalls, however,
      bacteria counts and pH were similar among treatments. Dry matter content of
      bedding did not differ among bedding treatments. Bacteria counts in bedding were
      positively correlated with teat skin swabs. Gram-negative bacteria and Klebsiella
      spp. counts on teat swabs were lower for cows housed on bedding treated with lime
      on d 2 compared with those for cows housed on control bedding and bedding that
      was replaced daily. Addition of lime to sawdust in the back one-third of tie
      stalls caused a decrease in exposure of teats to environmental mastitis pathogens
      in bedding for 1 d. Daily replacement of bedding had a minimal effect on bacteria
      counts in bedding and on teat skin.

PMID- 9276799
TI  - Computer-assisted sperm analysis for assessing initial semen quality and changes
      during storage at 5 degrees C.
AB  - Computer-assisted sperm analysis equipment was used to evaluate bull sperm
      initially in a modified Tyrode's solution, in Cornell University extender, and in
      egg yolk-glycerol-Tris extender (following cooling and storage in the latter two
      extenders). Two ejaculates of semen were collected from each of eight bulls.
      Semen was divided into aliquots using a factorial arrangement. The semen, diluted
      to approximately 20 x 10(6) sperm/ml, was loaded into two 20-micron chambers, and
      six microscope fields from each chamber were videotaped for each treatment of
      each ejaculate of semen. Eight sperm characteristics analyzed with the Hamilton
      Thorne integrated visual optical system (Hamilton Thorne, Beverly, MA) were
      reported, and some of these characteristics differed significantly among bulls.
      The initial values of motile sperm in modified Tyrode's solution, Cornell
      University extender, and egg yolk-glycerol-Tris extender were 87, 79, and 66%;
      little change followed cooling and storage at 5 degrees C in the latter two
      extenders. Also, there was a small but significant decline in sperm velocity
      during 3 d of storage. Hyperactive sperm increased slightly during storage. The
      procedures used can rapidly and accurately measure many sperm characteristics in
      fresh semen and in semen stored in egg yolk extenders, and differences among
      bulls can be detected.

PMID- 9276800
TI  - Visual discrimination in adult dairy bulls.
AB  - Adult Holstein-Friesian dairy bulls were trained to recognize a black disk and
      then to discriminate between that disk and smaller ones. The bulls learned these
      tasks, but much more slowly than did dairy calves. Achievement of a consistently
      high percentage of correct choices varied among bulls because of daily variation
      in the disposition of the bull, which seemed to affect willingness to concentrate
      on the experimental task. Nevertheless, all bulls demonstrated learning, and each
      bull remembered very well what he once had learned. A 36-cm disk was easily
      detected and discriminated from smaller disks. However, bulls were not able to
      discriminate between two disks that differed in area by less than a factor of 4.
      The ability to use visual cues, such as shapes and size of shapes, suggested that
      the visual system is important in the biology of bulls. The slow learning rate
      and the variability in the percentages of correct responses were not considered
      to be an indication of cognitive disabilities in general but rather a reflection
      of the daily disposition of the bull, which affected his willingness to
      cooperate.

PMID- 9276802
TI  - Minimum versus optimum concentrations of fiber in dairy cow diets based on barley
      silage and concentrates of barley or corn.
AB  - Six primiparous and 6 multiparous lactating Holstein cows were used in a double
      d6 x 6 Latin square to determine the effects of the percentage of forage fiber in
      diets containing concentrates based on barley or corn. Cows received one of six
      diets that provided three percentages of neutral detergent fiber (NDF) from
      barley silage [19.5, 25.0, and 40.9% of dry matter intake (DMI)] combined with
      concentrates based on either barley or corn. The DMI (18.6 vs. 18.3 kg/d) and net
      energy for lactation (27.2 vs. 26.8 Mcal/d) were similar for cows fed barley and
      corn diets, respectively. Consequently, milk yield (25.7 vs. 25.0 kg/d) and fat
      corrected milk yield (22.3 vs. 21.7 kg/d) were not affected by type of grain.
      Milk yields were similar for cows fed low and medium NDF diets, but yields
      declined when NDF from forage exceeded 25% of DMI because of declining intake of
      net energy for lactation. Effects of increased fiber from forage on milk fat
      content differed depending on diet; the low NDF diet based on barley caused milk
      fat to decline. Rumination time was higher for diets based on barley than for
      diets based on corn (516 vs. 469 min/d), and, as the percentage of forage fiber
      in the diet increased from low to high, rumination time increased more for cows
      fed diets based on corn than for cows fed diets based on barley. The minimum
      amount of forage fiber necessary in diets to avoid milk fat depression appeared
      to be higher for barley diets than for corn diets, although milk fat depression
      may not be a valid criterion by which to assess minimum fiber concentrations.
      Further research is needed to determine the minimum concentration of forage fiber
      needed to ensure healthy ruminal function and cow longevity.

PMID- 9276801
TI  - Correlation of acid detergent lignin and Klason lignin with digestibility of
      forage dry matter and neutral detergent fiber.
AB  - The acid detergent lignin and Klason lignin methods were compared for their
      correlation with forage digestibility. Thirty-six forages, including C3 legumes
      and C3 and C4 grasses, were analyzed for sulfuric acid detergent lignin, Klason
      lignin, and in vitro digestibilities of dry matter (DM) and neutral detergent
      fiber (NDF). Twenty of these forages were also fed to lambs at restricted intake
      for measurement of DM and NDF digestibilities. Lignin concentrations determined
      by the two lignin methods were positively correlated, and the Klason lignin value
      was always greater than the acid detergent lignin concentration. The largest
      differences were observed for grass forages. Digestibilities of forage DM and NDF
      were negatively correlated with both lignin methods for the in vitro system and
      the lamb digestibility trials. The degree of correlation for the two lignin
      methods with digestibility was generally similar across all forages and within
      forage classes. Slopes of linear regressions of digestibility on lignin
      concentration did not differ between legumes and grasses. Although the sulfuric
      acid detergent lignin and Klason lignin procedures gave very different estimates
      of forage lignin concentration, they were similarly correlated with digestibility
      and should yield predictions of forage digestibility that have similar accuracy.

PMID- 9276803
TI  - Effects of nonstructural carbohydrates and source of cereal grain in high
      concentrate diets of dairy cows.
AB  - Five primiparous and 5 multiparous Holstein cows were used in an experiment with
      a double 5 x 5 Latin square design to evaluate the effects of lowering the
      concentration of nonstructural carbohydrates in high grain diets on intake,
      chewing activities, digestibility, and yield and composition of milk. Cows
      received diets consisting of 30% barley silage (dry matter basis) and one of five
      isocaloric concentrates containing corn, hull-less barley, or barley, ranging in
      the percentage of nonstructural carbohydrates from 24 to 42%. Diet did not affect
      the dry matter intake (DMI) of primiparous cows. However, for multiparous cows,
      as the concentration of nonstructural carbohydrates in the corn diets was lowered
      from 34 to 30%, DMI increased from 16.3 to 18.9 kg/d (2.66 to 3.07% of body
      weight), and, as the concentration of nonstructural carbohydrates in the barley
      diets was lowered from 29 to 22%, DMI increased from 19.6 to 21.0 kg/d (3.09 to
      3.19% of body weight). For both groups of cows, a reduction in the nonstructural
      carbohydrates in either the corn or barley diets had minimal effects on milk
      yield, fat-corrected milk yield, fat content, and protein content, except that
      the fat content of milk from younger cows fed barley diets was lowered (2.70% vs.
      2.30%). For diets formulated at similar concentrations of nonstructural
      carbohydrates, grain source had no effect on DMI or digestible DMI, but milk
      yield was lower for cows fed the diet containing hull-less barley (25.2 kg/d)
      than for cows fed the diets containing corn (26.8 kg/d) or barley (28.1 kg/d).
      When the concentrations of nonstructural carbohydrates in high grain diets were
      reduced, feed intake was enhanced, but the relationship between the concentration
      of nonstructural carbohydrates and performance was not consistent. Differences in
      ruminal availability of carbohydrates need to be accounted for when diets are
      formulated on the basis of nonstructural carbohydrates using a range of cereal
      grains.

PMID- 9276804
TI  - Malate content of forage varieties commonly fed to cattle.
AB  - The objective of this study was to determine the concentration of malate in
      forage varieties at different stages of maturity. Five alfalfa varieties
      (Alfagraze, Apollo Supreme Cimarron, Crockett, and Magnum III) and three
      bermudagrass varieties (Coastal, Tifton-78, and Tifton-85) were collected at
      different stages of maturity. Samples were collected from replicate plots (n = 3)
      of each alfalfa variety at 9, 18, 28, 35, and 42 d of maturity; bermudagrass hay
      samples were composited from six bales of each variety from two cuttings staged
      to be harvested at 27 and 41 d of maturity. Malate was extracted from the samples
      and quantitated by high performance liquid chromatography using an organic acid
      column. As maturity increased, the concentration of malate declined in both plant
      species. Concentrations of malate were numerically higher in two alfalfa
      varieties (Crockett and Magnum III) at 35 and 42 d of maturity than in all other
      alfalfa varieties. Concentrations of malate in bermudagrass at 41 d of maturity
      were lower than concentrations of malate in all alfalfa varieties at 42 d of
      maturity. Malate declined as maturity increased in the Coastal and Tifton-78
      varieties. Because malate stimulates the utilization of lactate by the
      predominant ruminal bacterium Selenomonas ruminantium, some of the benefits
      associated with alfalfa in the diets of dairy cattle may be due to the malate in
      this forage.

PMID- 9276805
TI  - Effects of dietary forage source and amount of forage addition on intake, milk
      yield, and digestion for lactating dairy cows.
AB  - Lactating cows were used to determine the effects of increasing forage content
      from alfalfa (Medicago sativa L.) hay or Tifton 85 bermudagrass (Cynodon sp.) hay
      or Tifton 85 bermudagrass (Cynodon sp.) hay on dry matter intake (DMI), milk
      yield, and nutrient digestion. Forage proportions and neutral detergent fiber
      (NDF) content of diets were (dry basis) 1) 45% corn (Zea mays L.) silage
      (control), 33.5% NDF; 2) 15% bermudagrass hay and 30% corn silage, 39.5% NDF; 3)
      30% bermudagrass hay and 15% corn silage, 46.6% NDF; 4) 15% alfalfa hay and 30%
      corn silage, 35.5% NDF; or 5) 30% alfalfa hay and 15% corn silage, 33.5% NDF. The
      DMI was greater with alfalfa diets than with bermudagrass diets, with low hay
      diets than with high hay diets, and with the control diet than with the hay
      diets. Digestibility of NDF in bermudagrass diets was greater than that in
      alfalfa diets, in high hay diets than in low hay diets, and in hay diets than in
      the control diet. In vitro NDF digestion was most rapid for bermudagrass hay,
      intermediate for corn silage, and slowest for alfalfa hay. Results suggest that
      NDF from bermudagrass was digested more completely and rapidly than was NDF from
      corn silage or alfalfa, which improved the rate of passage despite the high NDF
      content of diets containing bermudagrass. Milk yield followed trends for DMI. The
      control diet and diets containing alfalfa elicited the greatest DMI and milk
      yield, but DMI per 100 kg of body weight for Holsteins was equal for diets
      containing either bermudagrass or alfalfa. High quality bermudagrass can be used
      in rations for lactating dairy cows.

PMID- 9276806
TI  - Nutrient fluxes in splanchnic tissue of dairy cows: influence of grass quality.
AB  - A crossover design was used to investigate the effects of high (450 kg of N/ha)
      or low (150 kg of N/ha) N fertilization of ryegrass on fermentation and nutrient
      fluxes in splanchnic tissue of dairy cows fed those grasses. Grass that was
      fertilized with the high amount of N contained more N and less sugar than did
      grass that was fertilized with less N. In rumen fluid, the concentration of NH3 N
      was lower for ryegrass that was fertilized with the low amount of N. The NH3
      release by portal-drained viscera and urea synthesis in the liver were higher for
      cows fed ryegrass that was fertilized with the high amount of N. The
      concentration of NH3 N in rumen fluid, NH3 N release in portal-drained viscera,
      urea synthesis in the liver, urea release from the liver, and urea concentrations
      in milk were highly correlated. The release of acetate and propionate in portal
      drained viscera was similar for both grasses and was well correlated with the
      proportion of volatile fatty acids in rumen fluid. The proportion of butyrate in
      rumen fluid was closely correlated with the release of butyrate and beta
      hydroxybutyrate in portal-drained viscera. Glucose synthesis in the liver
      indicated gluconeogenesis from amino acids, which corresponded well with urea
      synthesis in the liver. For the grass fertilized with more N, availability of
      energy sources for rumen microbes was low, and, therefore, cows did not use the N
      in that grass efficiently.

PMID- 9276807
TI  - Components of growth in Holstein heifers fed either alfalfa or corn silage diets
      to produce two daily gains.
AB  - Growth components were compared in an experiment with a 2 x 2 factorial design.
      Eight replicates of Holstein heifers were fed diets based on either alfalfa or
      corn silage for daily gain of either 725 or 950 g from 181 to 334 kg of body
      weight (BW). Mean daily gains from corn diets were greater than gains from
      alfalfa diets for BW, udder, empty body, fat, fat-free matter, protein, H2O, C,
      and energy but were less than gains from alfalfa for gut contents and ash. High
      daily gain produced higher mean values for all of these variables than did lower
      daily gain. The percentage of protein in fat-free matter was not affected by
      either main effect. The percentage of fat in empty body gain was increased as
      daily gain increased. Energy concentration of fat-free matter that was gained was
      not affected by either diet or daily gain. Energy concentration of empty body
      gain increased as daily gain increased. The percentage of gut contents in daily
      BW gain was higher for heifers fed the alfalfa diet than for those fed the corn
      diet. Energy concentration in daily BW gain was affected by diet and daily gain.
      Variations of fat and gut contents in daily BW gain must be considered when
      requirements or expected growth are described.

PMID- 9276808
TI  - Effects of heat treatment and physical processing of cottonseed on nutrient
      digestibility and production performance by lactating cows.
AB  - Four primiparous Holstein cows were used in an experiment with a 5 x 4 Youden
      square design. The effects of heat processing and particle size of cottonseed
      used in the diets of dairy cows were investigated. Dietary treatments were
      control (3.6% tallow, 4.5% casein), whole cottonseed, ground cottonseed, roasted
      whole cottonseed, and roasted ground cottonseed. Diets consisted of 55% corn
      silage, 1.54% urea, and cottonseed at 18.1% or dry matter. Cottonseeds were
      roasted at 149 degrees C and steeped for 30 min. Roasting increased the amount of
      ruminally undegradable protein measured in vivo, the ratio of ruminal acetate to
      propionate, pH, and milk protein percentage. Ruminal digestibilities of organic
      matter (OM) and neutral detergent fiber and biohydrogenation of fatty acids were
      reduced by roasting. The grinding of cottonseed increased the total tract
      digestibility of OM and N and tended to increase ruminally undegradable protein
      of cottonseed in vivo. Interactions between heat treatment and particle size of
      cottonseed revealed that roasted ground cottonseed resulted in the highest total
      tract digestibility of OM, N, and neutral detergent fiber. Utilization of
      cottonseed may be improved by heat or mechanical processing as was indicated by
      this study.

PMID- 9276809
TI  - Excretion of purine derivatives by Holstein cows abomasally infused with
      incremental amounts of purines.
AB  - Five multiparous, ruminally cannulated Holstein cows (two lactating and three
      dry) weighing (X +/- SD) 667 +/- 35 kg were used to study the effect of abomasal
      purine infusion on the excretion of purine derivatives. Cows were fed corn silage
      four times daily at 90% of ad libitum intake (X = 9.16 kg of dry matter/d).
      Purines were infused into the abomasum as brewer's yeast suspensions in five
      incremental amounts (0 to 380 mmol/d) during five experimental periods according
      to a 5 x 5 Latin square design. Periods were 7 d; purine infusions were conducted
      during the last 4 d, and urine was collected during the last 3 d of each period.
      Ruminal purine outflow in all cows was measured during an experimental period
      immediately preceding and immediately following the five infusion periods and in
      each cow during the 0-mmol/d infusion period of the experiment. The relationship
      between total (milk plus urine) daily excretion of purine derivatives (allantoin
      plus uric acid) and total (abomasal infusion plus ruminal outflow) daily purine
      flow was quantified by linear regression analysis and was described by the
      relationship: Y = 0.856X + 103 (r2 = 0.93). The slope (0.856) indicated that 86%
      of purines that reached the omasum were excreted as purine derivatives. In the
      two lactating cows, urinary purine derivatives accounted for 98.4% of the total
      purine derivatives that were excreted. Ruminal flow of microbial CP can be
      estimated from the CP:purine ratio of ruminal microorganisms and the excretion of
      purine derivatives.

PMID- 9276810
TI  - Effects of supplementation of energy or ruminally undegraded protein to lactating
      cows fed alfalfa hay or silage.
AB  - Alfalfa was harvested as silage or hay and fed in two 12-wk trials with a 4 x 4
      Latin square design that used 12 (trial 1) or 24 (trial 2) multiparous lactating
      cows (4 ruminally cannulated cows per trial). Diets contained (dry matter basis)
      75 or 50% alfalfa plus 24 of 40% high moisture corn (trial 1) or 50% alfalfa, 44
      or 41% high moisture corn, with (3%) or without fish meal (trial 2). Experiments
      were conducted to evaluate the responses of cows fed alfalfa hay or alfalfa
      silage diets to an increase in protein supply from microbial protein synthesis
      (trial 1) or from the supplementation of ruminally undegraded protein (RUP)
      (trial 2). In trial 1, the increase in high moisture corn in the diet increased
      both milk protein and microbial crude protein yields (estimated from the
      excretion of purine derivatives) to a greater extent for the cows fed the alfalfa
      silage diets (170 and 337 g/d, respectively) than for the cows fed the alfalfa
      hay diets (100 and 100 g/d, respectively). In trial 2, RUP supplementation (as
      fish meal) increased milk protein yield 100 g/d for cows fed alfalfa silage diets
      and 20 g/d for cows fed alfalfa hay diets. These results indicated that protein
      status was poorer and, thus, more responsive to absorbable protein from microbial
      protein (trial 1) or RUP (trial 2) for cows that consumed alfalfa conserved as
      silage versus those that consumed alfalfa conserved as hay.

PMID- 9276811
TI  - Adequacy of amino acids in diets fed to lactating dairy cows.
AB  - The Cornell Net Carbohydrate and Protein System was used to evaluate absorbable
      limiting amino acids (AA) for milk yield. The system was utilized to characterize
      whether diets in five previous experiments met AA requirements for milk protein
      synthesis. Twenty-nine treatment means for milk yield from 367 cows constituted
      the database for the evaluation. Using the mechanistic relationships of nutrient
      metabolism described in the Cornell system, absorbed amounts were predicted of
      each essential AA from a diet and milk yields allowed by the most limiting AA.
      Regression of observed milk yield (Y) on predicted milk yield (X) using all
      treatment means (n = 29) was Y = 2.3 + 0.799X (r2 = 0.72). The linear
      relationship was stronger using 6 treatment means (n = 18) when protein
      supplements were fed rather than when ruminally protected AA were fed or when AA
      were postruminally infused (Y = -1.8 + 0.983X; r2 = 0.93). The Cornell system
      predicted that, for diets based on corn, Met or Lys was limiting when soybean
      meal was the protein source, but Lys was limiting when corn gluten meal or
      brewers grains were the source of protein. By AA limitation, the Cornell system
      explained differences in milk yield for diets that differed in supplemental
      protein sources in some of the experiments. As determined from milk protein
      yields in these studies, requirements for individual essential AA were expressed
      as a percentage of dietary dry matter or total essential AA, and values were
      relatively constant among dietary treatments and experiments.

PMID- 9276812
TI  - Particle size of roasted soybeans and the effect on milk production of dairy
      cows.
AB  - Fifteen cows were used in an experiment with a 5 x 5 replicated Latin square
      design to quantify the effect of particle size of roasted soybeans on milk
      production and fecal excretion of soybeans. The five experimental periods were
      each 2 wk long. Diets contained (percentage of dry matter) 33% alfalfa silage,
      17% corn silage, 30.6% high moisture ear corn, 18% soybeans, and 1.4% mineral
      supplement. The five dietary treatments included raw whole soybeans or roasted
      soybeans in four particle sizes (whole and half, half and quarter, quarter and
      smaller, and coarsely ground). Mean particle sizes of the raw soybeans and of the
      roasted soybeans in whole and half sizes were > 4.75 mm. Mean particle sizes of
      the roasted soybeans in half and quarter, quarter and smaller, and coarsely
      ground roasted soybeans were 2.92, 2.01, and 1.59, respectively. During the
      normal handling of roasted soybeans, a large number of seeds was broken into
      halves in the treatment with whole and half sizes (36%, wt/wt basis). Production
      of 3.5% fat-corrected milk was 35.4, 37.7, 37.2, 35.1, and 35.4 kg/d for cows fed
      raw soybeans; roasted soybeans in whole and half, half and quarter, and quarter
      and smaller sizes; and ground roasted soybeans, respectively. Cows that were fed
      raw soybeans excreted the largest amount of visible soybean particles in feces,
      and cows that were fed ground roasted soybeans had the least amount of soybeans
      in the feces (61.3 vs. 10.6 g of soybeans/kg of fecal dry matter). Roasted
      soybeans in half and quarter sizes are optimal for milk production.

PMID- 9276813
TI  - Effect of vitamin E supplementation in diets with a low concentration of selenium
      on mammary gland health of dairy cows.
AB  - Sixty-six cows and heifers (Holsteins and Jerseys) were assigned to one of three
      treatments at 60 d before anticipated calving. Treatment 1 consisted of 100 IU/d
      of supplemental vitamin E during the dry period and 100 IU/d during the first 30
      d of lactation. Treatment 2 was 1000 IU/d of vitamin E during the dry period and
      500 IU/d during lactation. Treatment 3 was 1000 IU/d of vitamin E during the
      first 46 d of the dry period, 4000 IU/d during the last 14 d of the dry period,
      and 2000 IU/d during lactation. Plasma concentrations of alpha-tocopherol
      decreased at calving for cows fed dietary treatments with low or intermediate
      concentrations of vitamin E, but not for cows fed the high vitamin E treatment.
      High dietary vitamin E increased concentrations of alpha-tocopherol in blood
      neutrophils at parturition, but no difference was found for the other two
      treatments. The percentage of quarters with new infections at calving was not
      different (32.0%) between cows receiving treatments that contained low and
      intermediate concentrations of vitamin E but was reduced (11.8%) in cows
      receiving the high vitamin E treatment. Clinical mastitis affected 25.0, 16.7,
      and 2.6% of quarters during the first 7 d of lactation for cows receiving the
      low, intermediate, and high vitamin E treatments, respectively. Cows with plasma
      concentrations of alpha-tocopherol < 3.0 micrograms/ml at calving were 9.4 times
      more likely to have clinical mastitis during the first 7 d of lactation than were
      cows with plasma concentrations of alpha-tocopherol > 3.0 micrograms/ml.

PMID- 9276814
TI  - Native corn starch versus either cellulose or glucose in the diet and the effects
      on apparent magnesium absorption in goats.
AB  - The objective of this study was to determine whether dietary glucose or starch
      would reduce the inhibitory effect of high K intake on Mg absorption in
      ruminants. In a 6 x 6 Latin square design, six goats were fed diets with or
      without added KHCO3 containing either cellulose, glucose, or native corn starch.
      The K concentrations of the diets were 7.8 or 34.0 g or K/kg of dry matter, and
      carbohydrates were incorporated so that their concentrations were identical on a
      glucose equivalent basis (331 g of glucose/kg of dry matter). The intake of extra
      K significantly reduced apparent Mg absorption from 29.8 to 22.1% on average.
      Glucose, instead of cellulose, in the diet did not affect Mg absorption.
      Replacement of dietary cellulose by corn starch enhanced the mean efficiency of
      Mg absorption from 21.8 to 30.9%. Starch versus glucose increased Mg absorption
      by 5.8 percentage units. No statistically significant interaction was observed
      between the type of carbohydrate and the amount of K in the diet with regard to
      Mg absorption. This study showed that the inhibitory effect of dietary KHCO3 on
      Mg absorption in goats was fully counteracted by the replacement of cellulose
      with starch in the diet. Possible changes in the pH of ruminal fluid might have
      mediated the dietary effects on Mg absorption.

PMID- 9276815
TI  - Performance and glucose metabolism in calves fed a chromium-nicotinic acid
      complex or chromium chloride.
AB  - Twenty-four Holstein bull calves were fed a milk replacer diet to assess the
      effects of Cr on calf performance and metabolism of glucose. Treatments consisted
      of no supplemental Cr (control) or 0.4 mg/kg of dry matter of supplemental Cr
      from CrCl3 or from a Cr-nicotinic acid complex. Supplementation with the Crt
      nicotinic acid complex increased the average daily gain and feed efficiency from
      d 28 to 42, but not over the entire 63-d performance phase. Calves that were fed
      diets supplemented with CrCl3 or the Cr-nicotinic acid complex had lower plasma
      glucose concentrations at 45 to 180 min after an i.v. infusion of insulin than
      did controls. Calves fed diets supplemented with the Cr-nicotinic acid complex
      also had lower plasma glucose concentrations from 90 to 180 min after insulin
      challenge than did calves that were fed diets supplemented with CrCl3. After an
      i.v. infusion of glucose, calves that were fed diets supplemented with CrCl3 had
      lower serum insulin concentrations at 10 to 25 min after challenge than did
      controls or calves that were fed diets supplemented with the Cr-nicotinic acid
      complex. However, the glucose clearance rate after glucose infusion was not
      affected by Cr supplementation. Chromium supplementation did not markedly affect
      the performance of calves, but the Cr-nicotinic acid complex and CrCl3 did
      intensify the response to insulin administered i.v.

PMID- 9276816
TI  - Body weight gain, feed efficiency, and fecal scores of dairy calves in response
      to galactosyl-lactose or antibiotics in milk replacers.
AB  - Holstein bull calves (n = 96) were purchased at approximately 7 d of age and were
      assigned to receive 400, 450, 500, and 550 g/d of milk replacer solids during wk
      1 to 4, respectively. Treatments were nonmedicated milk replacer plus dried whey,
      medicated milk replacer (138 mg/kg of oxytetracycline and 276 mg/kg of neomycin)
      plus dried whey, or nonmedicated milk replacer plus whey processed with beta
      galactosidase to contain 15% galactosyl-lactose. Processed whey was added to
      provide 1% of dry matter as galactosyl-lactose; an equivalent amount of dried
      whey was added to the other treatments to provide 6.3% of dry matter daily.
      Intake of milk replacer and fecal scores were measured daily. No calf starter or
      hay was fed. Body weights were measured weekly from arrival to 26 d. Serum
      immunoglobulin G, measured 1 d after arrival, averaged 18.3 g/L. Intake of milk
      replacer plus additive during the 26-d study was 445 g/d and did not vary with
      treatment. Body weight and body weight gain were increased by 52 and 72 g/d in
      response to antibiotics and galactosyl-lactose, respectively. Severity of scours
      and number of days scouring tended to be reduced when calves were fed milk
      replacer containing galactosyl-lactose or antibiotics.

PMID- 9276817
TI  - Modeling the effect of a disease on culling: an illustration of the use of time
      dependent covariates for survival analysis.
AB  - This study demonstrated five different approaches, with and without time
      dependent covariates, to determine the effect of disease on culling. It was also
      of interest to determine whether the time of the disease had an effect on
      subsequent culling (i.e., whether disease should be treated as time-dependent
      covariate). To this purpose, five separate models were studied: Models 1 through
      4 were Cox proportional hazards models, and Model 5 was a Weibull model. Model 1
      treated disease as a binary, time-independent covariate. Model 2 treated disease
      as a time-dependent covariate, and one change of status was assumed to occur at
      the time of disease. Model 3 also assumed that one change in status occurred at
      the time of disease, but the effect of that change was assumed to be different
      depending on when the disease occurred. Models 4 (Cox) and 5 (Weibull) assumed an
      interaction between the occurrence of disease (time of disease) and the
      occurrence of culling (time of culling). As an illustration, the effect of
      mastitis on culling was studied for 2998 Holstein dairy cows in 10 herds. Parity
      and previous 305-d milk yield were also included as covariates; the data were
      stratified by herd. For all models, mastitis was a significant factor for
      culling. The significance tests for the estimates from Models 4 and 5
      demonstrated that the hazard of culling differed for different stages of
      lactation, depending on when mastitis had occurred and when its effect on culling
      occurred; that is, time dependence exists between time of mastitis and time of
      culling.

PMID- 9276818
TI  - Genetic association between parameters of inmate immunity and measures of
      mastitis in periparturient Holstein cattle.
AB  - Relationships between genetic measures of mastitis (somatic cell score, score for
      clinical mastitis, and scores for IMI with major or minor pathogens) and
      immunological parameters (physiological and molecular markers) were examined for
      periparturient Holstein cows. Physiological markers included 11 in vitro
      immunological assays. Molecular markers included the second exon of the DRB3
      locus of the bovine major histocompatibility complex, the IgG2 isotype genotype,
      and the CD18 genotype (the locus responsible for bovine leukocyte adhesion
      deficiency). A gene substitution model was used to estimate the additive genetic
      effects of alleles of the three molecular markers on estimated breeding value
      (EBV) for mastitis measures. Pearson correlation coefficients between EBV for
      immunological assays and EBV for mastitis measures were computed. Molecular
      markers explained up to 40% of the variation in EBV for measures of mastitis. The
      presence of allele DRB3.2*16 was associated with higher EBV for SCS. Allele
      DRB3.2*8 was associated with increased EBV for clinical mastitis, as was the
      IgG2b allele and the normal CD18 allele. Alleles DRB3.2*11, *23, IgG2a, and the
      recessive allele for bovine leukocyte adhesion deficiency were associated with
      decreased clinical mastitis. A positive genetic association was found between
      allele DRB3.2*24 and EBV for IMI by major pathogens and between DRB3.2*3 and IMI
      by minor pathogens. Several correlations between EBV for immunological assays and
      EBV for mastitis measures were significantly different from 0. Cows with low EBV
      for SCS tended to have neutrophils that had greater functional ability at maximal
      immunosuppression, low serum IgG1, and high numbers of circulating mononuclear
      cells. Immunological parameters, including physiological and molecular markers,
      are useful aids to understand the genetics of resistance to mastitis.

PMID- 9276819
TI  - Effects of milk protein genotypes on the variation for milk production traits of
      Holstein and Jersey cows in California.
AB  - The objectives of this study were to form appropriate composite kappa-beta
      alpha(s1)-CN genotypes in order to assess which genotypes were favorably
      associated with first lactation milk production, fat and protein percentages, and
      fat and protein production for data of 916 Holstein and 116 Jersey cows. Multiple
      trait animal models were used with assumed fixed effects for herd, year and
      season of calving, age at calving, days open, composite kappa-beta-alpha(s1)-CN
      genotypes, and beta-LG genotypes. The differences between the beta-LG genotypes
      for production traits were not statistically significant for either breed. The
      proportion of phenotypic variance that was due to the composite kappa-beta
      alpha(s1)-Cn genotypes was 5% for milk production, 4% for protein production, and
      3% for fat percentage. The kappa-beta-alpha(s1)-CN genotype ABA1A2BB was superior
      to the comparable AAA1A2BB and ABA1A1BB genotypes by 252 and 338 kg for first
      lactation milk yield, respectively, and 8.7 and 11.5 kg for protein yield,
      respectively. Thus, neither the beta-CN A2 allele nor the kappa-CN B allele alone
      had a positive effect on milk and protein production, but the joint effect was
      strongly positive. These results may be explained by epistatic effects between
      the kappa-CN and beta-CN loci and possibly by closely linked quantitative trait
      loci with favorable alleles on the kappa-beta-alpha(s1)-CN BA2B haplotype.

PMID- 9276820
TI  - Realized versus expected gains in milk and fat production of Holstein cattle,
      considering the effects of days open.
AB  - The objective of this study was to determine whether differences in first
      lactation production, unadjusted or adjusted for days open, were correctly
      predicted by pedigree estimates for two lines of Holstein cattle. Data on 875
      cows from two selection lines were collected from 1970 to 1988. Lines were
      created by mating foundation females of high or low pedigree merit to sires
      selected for high or average PTA milk. Both lines were managed identically to
      minimize environmental differences. The number of days open was analyzed with a
      fixed effects model containing year, season, interaction of year and season, sire
      line, foundation group, and interaction of sire line and foundation groups. The
      high milk line had significantly more days open than did the average line.
      Adjusted and unadjusted records for milk and fat were analyzed with the model
      described previously, plus the interaction of sire line and year. Least squares
      means and estimates for mean parent average were used to calculate realized and
      expected differences in production between lines within and across years.
      Adjustment of records for days open reduced estimates of realized gain, but not
      significantly. Regressions of realized gain on expected gain indicated that
      expected gains were matched or exceeded by unadjusted or adjusted realized gain.

PMID- 9276821
TI  - A computationally feasible test day model for genetic evaluation of yield traits
      in the United States.
AB  - A multitrait analysis of test day yields is proposed that includes 60 traits [3
      yield traits (milk, fat, and protein), 2 parity groups (first and later) per
      yield trait, and 10 stages of lactation per parity]. To reduce the computations
      needed for the 60 traits, test day effects are estimated within the herd before
      analysis across herds, the rank of t he genetic (co)variance matrix is reduced, a
      canonical transformation is used with missing values replace by their
      expectations, and a repeatability model is applied to allow inclusion of parities
      after second. Historical 305-d records are included through their correlations
      with test day effects. Possible benefits from this model include 1) more accurate
      estimation of environmental effects from including the influence of particular
      days of recording, 2) optimal use of information from all test days (especially
      for lactations with long intervals from calving to first test or between tests),
      3) improved accuracy of evaluations for component yields through contributions
      from information for milk yield, and 4) greater stability of bull evaluations
      from accounting for genetic differences among daughters in the shape of lactation
      curve and maturity rate.

PMID- 9276822
TI  - Estimation of (co)variance components for Jersey type traits using a
      repeatability model.
AB  - (Co)variance components for final score and 15 linear types traits of Jersey cows
      were estimated by multitrait REML using multiple diagonalization and a
      repeatability model with 34,999 records of 22,354 cows. Multiple diagonalization
      gave relative off-diagonals (ratio of squared off-diagonals to the product of
      diagonals) of < 0.1%. Heritabilities and repeatabilities, respectively, were
      estimated as 0.29 and 0.48 for final score, 0.40 and 0.57 for stature, 0.26 and
      0.39 for strength, 0.28 and 0.43 for dairy form, 0.13 and 0.25 for foot angle,
      0.13 and 0.25 for rear legs (side view), 0.27 and 0.41 for body depth, 0.31 and
      0.52 for rump angle, 0.22 and 0.33 for thurl width, 0.22 and 0.36 for fore under
      attachment, 0.28 and 0.46 for rear udder height, 0.26 and 0.42 for rear udder
      width, 0.32 and 0.48 for udder depth, 0.20 and 0.36 for udder cleft, 0.29 and
      0.46 for front teat placement, and 0.31 and 0.48 for teat length. Estimates of
      heritability generally were higher, and estimates of repeatability were lower,
      than values used previously for USDA genetic evaluations, which were based on
      data from the 1970s and early 1980s. Final score was highly correlated both
      genetically and phenotypically with dairy form and rear udder traits. These
      estimates of heritabilities and (co)variance components are necessary for
      multitrait genetic evaluation of linear type traits of US Jerseys.

PMID- 9276823
TI  - Relationship between United States and Canadian genetic evaluations of longevity
      and somatic cell score.
AB  - Canadian and US evaluations of Holstein bulls were compared for longevity
      measures (433 bulls) and somatic cell score (354 bulls). Bulls were required to
      have a birth year of > or = 1975, daughter information from > or = 20 herds, and
      a reliability of > or = 50% in both Canada and the US. The number of bulls with
      longevity evaluations was greater for early years because longevity information
      was available from lactation data and daughters were required to be > or = 3 yr
      of age for US evaluations; evaluations for somatic cell score required additional
      collection of data and did not have corresponding numbers of bulls until the
      1980s. Correlation between longevity measures in the US (productive life) and
      Canada (herd life) was 0.60. This low correlation was expected because US
      productive life includes yield information, but yield is excluded from Canadian
      herd life. For evaluations for somatic cell score, the correlation between the
      two countries was 0.82. Genetic correlations with productive life were estimated
      to be 0.69 for herd life and 0.81 for herd life combined with protein yield.
      Conversion equations were developed to predict a US evaluation for somatic cell
      score from a Canadian evaluation for somatic cell score and to predict a US
      evaluation for productive life from Canadian evaluations for herd life and yield.

PMID- 9276824
TI  - Estimation of variance components for somatic cell counts to determine thresholds
      for uninfected quarters.
AB  - The objective of this study was to determine the factors affecting somatic cell
      count (SCC), to estimate variance components of these factors, and to calculate
      and evaluate the thresholds for intramammary infection based on SCC. The
      infection status from 22,467 quarter milk samples from 544 cows in seven herds
      was determined. Infections status was the most important factor affecting SCC.
      The increase in SCC was more pronounced for major pathogens than for minor
      pathogens. Even after adjustment for infection status, the interaction between
      stage of lactation and parity was significant. For culture-negative samples
      within a lactation, the shape of the SCC curve was inversely related to the shape
      of the milk production curve. The shape of the SCC curve was flat for first
      lactation cows compared with the shape of the SCC curve for cows in subsequent
      lactations. The effect of clinical mastitis on SCC was significant. The use of
      SCC thresholds for specific parities and stages of lactation to detect
      intramammary infection improved quality parameters only slightly over a fixed
      threshold of 200,000 cells/ml.

PMID- 9276825
TI  - Evaluation of two iodophor teat germicides: activity against Staphylococcus
      aureus and Streptococcus agalactiae.
AB  - Two germicides containing 0.5 and 1% titratable iodine were tested for efficacy
      against the development of new intramammary infections (IMI) caused by
      Staphylococcus aureus and Streptococcus agalactiae. The two trials for
      postmilking teat dip used a model for experimental challenge that was recommended
      by the National Mastitis Council. The 0.5% iodine formulation reduced new Staph.
      aureus IMI by 78.2% and reduced new Strep. agalactiae IMI by 73.2%. The 1% iodine
      product reduced new Staph. aureus IMI by 43.5% and reduced new Strep. agalactiae
      IMI by 46.4%. No adverse effects on the condition of teat skin or on teat ends
      were observed over the course of the trials. At the completion of each trial, the
      teat skin of dipped quarters was characterized as normal, smooth skin that was
      free from scales, cracks, or chapping; the teat orifice was characterized as
      smooth without evidence of irritation.

PMID- 9276826
TI  - Immunobiology of the mammary gland.
AB  - The mammary gland is a complex organ that provides neonatal offspring with milk
      for nourishment and disease resistance. Specific and innate immune factors
      associated with mammary gland tissues and secretion also play a vital role in
      protecting the gland from infectious disease. Through genetic selection and
      technological advances in milk removal, the bovine mammary gland yields for more
      milk than is needed to nourish the newborn calf. This excess is the basis of the
      dairy industry. Factors associated with the intense management of dairy cattle
      can profoundly affect mammary gland immunity and the ability of the host to
      resist mastitis. Technological advances in immunology have led to the
      availability of new research tools that can facilitate the study of mammary gland
      immunity and disease pathogenesis. In recent years, considerable research effort
      has focused on enhancing the natural defense mechanisms of the mammary gland
      during periods of heightened susceptibility to disease. This paper provides a
      comprehensive overview of mammary gland immunity with special emphasis on the
      bovine system. The underlying mechanisms of disease susceptibility and
      development of potential immunoregulatory strategies to control mastitis are
      discussed.

PMID- 9276827
TI  - Planning the milking center in expanding dairies.
AB  - This paper focuses on dairies that want to expand and milk more cows through an
      existing parlor or by building new parlor. The expansion process can be divided
      into the following three phases: 1) financial evaluation, 2) design, and 3)
      construction. A financial evaluation should be carried out first to determine the
      resources that are available for expanding the dairy operation. This phase is
      extremely important, considering that 68% of the dairies that expand have cash
      flow problems within the first 2 yr of operation. The next phase is to design the
      milking center, and options include expanding the present parlor or constructing
      a new parlor. The present parlor can be expanded by addition of stalls, but group
      size must also expand to maintain cow flow at the larger parlor size. Group size
      can often be increased by combining corrals or free-stall alleys. The third phase
      in the expansion is to determine the most efficient milking procedure during the
      construction or remodeling of the facilities.

PMID- 9276828
TI  - Prediction of developmental patterns through 40 months from 6- and 12-month
      neurologic examinations in very low birth weight infants.
AB  - This study examines whether neurologic examinations at 6 and 12 months of age can
      predict developmental patterns in very low birth weight infants and fullterm
      controls through 40 months of age. We performed neurologic examinations at 6 and
      12 months; the Bayley Scales of Infant Development at 6, 12, and 24 months; and
      the Stanford-Binet and the McCarthy Motor scale at 40 months. The very low birth
      weight infants were categorized on the basis of socioeconomic status and high or
      low risk for early medical complications. More abnormal neurologic scores
      predicted greater deceleration of cognitive development for high-risk infants
      only. The 12-month neurologic examination predicted the degree of deceleration in
      motor development. Medical risk was an independent predictor of curvature of the
      psychomotor development curve. We conclude that neurologic examinations during
      the 1st year of life might be used with other factors in decision concerning
      referrals to early-intervention programs.

PMID- 9276829
TI  - Swaddling after heel lance: age-specific effects on behavioral recovery in
      preterm infants.
AB  - We examined responses of preterm infants to swaddling after a heel lance. Fifteen
      preterm infants from two postconceptional age (PCA) groups (Group 1: n = 7, PCA <
      31 wk; Group 2: n = 8, PCA > or = 31 wk) were observed for 30 minutes during
      blood sampling followed by routine care; blood sampling followed by swaddling;
      and no blood sampling and routine care. In both groups, blood sampling resulted
      in concurrent increases in heart rate and state of arousal, in negative facial
      displays, and in reductions in blood oxygensaturation. After the blood was drawn,
      infants less than 31 weeks PCA exhibited an immediate and spontaneous return to
      behavioral patterns similar to those observed during the no-blood-sample
      condition, regardless of treatment condition. Infants 31 weeks PCA or older
      exhibited protracted behavioral disturbance that was significantly reduced by the
      use of swaddling. We discuss the significance of these findings.

PMID- 9276830
TI  - Sibling Adaptation to Childhood Cancer Collaborative Study: the association of
      sibling adaptation with maternal well-being, physical health, and resource use.
AB  - This multi-institutional study investigated the association of
      behavioral/emotional adaptation among siblings of children with cancer with
      maternal general well-being, physical health, and resource use. One hundred
      seventy siblings and mothers completed standardized interviews and self-report
      measures 6 to 42 months after the cancer was diagnosed. As a group, mothers of
      children with cancer reported significantly lower levels of well-being than
      matched controls. When stratified according to the level of the sibling's
      behavioral/emotional adaptation, mothers of siblings in the Dysfunctional group
      (1) reported the lowest levels of well-being; (2) during the preceding year, were
      more likely to have sought professional services than mothers of children in the
      Resilient group; and (3) were least likely to have found social support helpful.
      Our results support an association between maternal well-being and sibling
      adjustment but show it is unlikely that nonspecific social support will improve
      adjustment. The rationale for problem-solving training for mothers is provided.

PMID- 9276831
TI  - Psychosocial consequences of bone marrow transplantation in donor and nondonor
      siblings.
AB  - We investigated the psychosocial effects of bone marrow transplantation (BMT) on
      siblings of transplant recipients. We asked how donor siblings compared with
      nondonor siblings on quantitative measures of behavior, psychological distress,
      and sense of self. Participants included 44 siblings (21 donors and 23 nondonors,
      ages 6-18 yr) of surviving pediatric BMT patients. On self-report measures,
      donors reported significantly more anxiety and lower self-esteem than nondonors.
      On teacher-rated scales, donors showed significantly more adaptive skills in
      school. On these same scales, nondonors showed significantly more school problems
      than donors. One-third of the siblings in each group reported a moderate level of
      post-traumatic stress reaction. Exploratory multiple regression analyses point to
      factors that might influence sibling adjustment and suggest counseling strategies
      and avenues for future research.

PMID- 9276832
TI  - Measuring inhibitory control in children.
AB  - The Stop Signal Task is a measure of inhibitory control in which subjects must
      press a button in response to a stimulus. On certain trials, the subject receives
      a second stimulus (the Stop Signal) after the primary stimulus and must withhold
      his/her response during those trials. The onset of the Stop Signal is varied,
      sometimes coming immediately after the primary stimulus (inhibition is easy); at
      other times, the Stop Signal arrives quite late, making inhibition difficult.
      Results from the Stop Signal Task were obtained from children with attention
      deficit/hyperactivity disorder (ADHD) and from controls; children with ADHD had
      significantly more difficulty inhibiting their responses than did controls. In a
      second study, results from the Stop Signal Task were obtained from a large sample
      of both behaviorally disturbed and community children; variables from the Stop
      Signal Task correlated well with both laboratory observations and teacher ratings
      of inattention and hyperactivity.

PMID- 9276833
TI  - Convergence between temperament ratings in early infancy.
AB  - This study assesses the degree of convergence between two temperament
      questionnaires promoted for use with relatively young infants. The mothers of 90
      normal, healthy infants were asked to complete the infant Behavior Questionnaire
      (IBQ) and the Early Infancy Temperament Questionnaire (EITQ) when their babies
      were approximately 3 months of age; the returned questionnaires were reduced into
      the dimensions defined by the instruments' authors. The EITQ includes a General
      Impressions rating scale that provides a more global estimate of the same
      temperament dimensions, and these scores were also examined. Infant ratings on
      both questionnaires were similar in magnitude to results of other published
      reports. Comparisons across instruments showed that the IBQ and EITQ seem to
      measure similar aspects of behavioral style, because all of the IBQ dimensions
      were significantly related to the appropriate EITQ dimensions. These results
      support the validity of both questionnaires for use with infants in the first
      months of life.

PMID- 9276834
TI  - The implications of welfare reform for developmental and behavioral pediatrics.

PMID- 9276835
TI  - Cyclic vomiting.

PMID- 9276836
TI  - Attention-deficit/hyperactivity disorder, self-regulation, and time: toward a
      more comprehensive theory.
AB  - This article describes the current clinical view of attention
      deficit/hyperactivity disorder (ADHD) and suggests a model of prefrontal lobe
      executive functions that explains better than current theories the cognitive and
      behavioral deficits associated with ADHD. The model shows how behavioral
      inhibition is related to and necessary for the proficient performance of four
      executive functions that subserve self-regulation: nonverbal working memory; the
      internalization of speech; the self-regulation of affect, motivation, and
      arousal; and reconstitution. These functions permit the construction, execution,
      and control of behavior by internally represented information, which removes
      behavior from control by the immediate context and brings it under the control of
      time. ADHD disrupts this process and returns control of behavior to the temporal
      now. A blindness to past, future, and time more generally, as well as an
      inability to direct behavior toward the future and to sustain it are among many
      of the deficits predicted by this model for persons with ADHD.

PMID- 9276837
TI  - The limbic system: an anatomic, phylogenetic, and clinical perspective.
AB  - The limbic system is the border zone where psychiatry meets neurology. The
      authors provide a model of limbic function that combines phylogenetic, anatomic,
      functional, and clinical data to interpret diseases relevant to neuropsychiatry.
      They provide evidence supporting two major divisions in the limbic system: a
      paleocortical division with the amygdala and orbitofrontal cortex at its center,
      and an archicortical division with the hippocampus and cingulate cortex at its
      center. The implicit integration of affect, drives, and object associations is
      the function of the paleocortical limbic division; explicit sensory processing,
      encoding, and attentional control is the function of the archicortical limbic
      division. The two work in concert to integrate thought, feeling, and action.
      Understanding their development and organization informs us about how best to
      care for our patients.

PMID- 9276839
TI  - The thalamus and neuropsychiatric illness.
AB  - Although the cerebral cortex is usually thought of as a likely substrate for
      psychiatric disease, the close relationship of thalamus to cortex, both
      structurally and functionally, argues for much closer consideration of this
      structure in both research and clinical settings. Four thalamic nuclei with
      widely differing functions are considered in terms of the specific roles they
      appear to play in central nervous system activity and their possible roles in
      psychiatric disease. These nuclei include the ventrobasal complex, the nucleus
      reticularis thalami, the mediodorsal nucleus, and the dorsal thalamic system with
      special reference to the habenula.

PMID- 9276838
TI  - Ventromedial temporal lobe anatomy, with comments on Alzheimer's disease and
      temporal injury.
AB  - The ventromedial temporal area has a complicated topography and neuroanatomy that
      has yielded secrets only grudgingly. The major features of surface topography are
      reviewed here as well as recent neuroanatomical findings that establish the
      ventromedial temporal area as both a recipient of cortical input and the origin
      for widespread output back to the cortex. The devastating involvement of all
      ventromedial temporal areas in Alzheimer's disease is highlighted, and comments
      are offered on the tentorium cerebelli and on mechanical injury to the area.

PMID- 9276840
TI  - The accumbens: beyond the core-shell dichotomy.
AB  - This article highlights recent discoveries related to the accumbens and closely
      associated structures, with special reference to their importance in
      neuropsychiatry. The development of "striatal patches" in the accumbens is
      reviewed in a series of pictures. Neuronal ensembles are discussed as potentially
      important functional-anatomical units. Attention is also drawn to recent
      discoveries related to the neuronal circuits that the primate accumbens
      establishes with the mesencephalic dopamine system. On the basis of histological
      and neurochemical differences, the accumbens has been divided into core and shell
      compartments. In the context of this article, the shell, which is an especially
      diversified part of the accumbens, is the subject of special attention because of
      its close relation to the extended amygdala and distinctive response to
      antipsychotic and psychoactive drugs.

PMID- 9276841
TI  - Neurobiology of fear responses: the role of the amygdala.
AB  - Evidence from many different laboratories using a variety of experimental
      techniques and animal species indicates that the amygdala plays a crucial role in
      conditioned fear and anxiety, as well as attention. Many amygdaloid projection
      areas are critically involved in specific signs used to measure fear and anxiety.
      Electrical stimulation of the amygdala elicits a pattern of behaviors that mimic
      natural or conditioned fear. Lesions of the amygdala block innate or conditioned
      fear, as well as various measures of attention, and local infusions of drugs into
      the amygdala have anxiolytic effects in several behavioral tests. N-methyl-D
      aspartate (NMDA) receptors in the amygdala may be important in the acquisition of
      conditioned fear, whereas non-NMDA receptors are important for the expression of
      conditioned fear. The peptide corticotropin-releasing hormone appears to be
      especially important in fear or anxiety and may act within the amygdala to
      orchestrate parts of the fear reaction.

PMID- 9276842
TI  - Paroxysmal limbic disorders in neuropsychiatry.
AB  - Patients who experience episodes with a transient disturbance in perception,
      memory, mood, and level of anxiety are frequently encountered by neurologists,
      psychiatrists, and psychologists. The possibilities for differential diagnosis of
      these episodes include partial complex epilepsy, psychogenic seizures, panic
      disorder, dissociative states, migraine, and transient global amnesia, among
      others. The clinical history may be vague and confusing, making it difficult to
      determine definitively the etiology of the events. This article describes a
      spectrum of paroxysmal disorders involving limbic structures, highlighting the
      clinical features and assessment techniques that aid in diagnosis and treatment.
      Clinical-anatomic correlations are provided whenever possible.

PMID- 9276843
TI  - Auras and experiential responses arising in the temporal lobe.
AB  - Complex partial seizures and the auras that precede them are often manifestations
      of localized temporal lobe activity. Auras, unlike complex partial seizures, are
      reportable, since memory for them is retained. Similar experiences can be
      elicited by local electrical stimulation of mesial or lateral temporal cortex.
      Auras and "experiential phenomena" arising in the temporal lobe reflect
      dissociation of human experience into perceptual, mnemonic, and affective
      components, which in some cases can be specifically localized. Auras often
      persist following medial temporal lobe surgery, even when patients are rendered
      seizure-free. This suggests that these auras, like formed memories, are widely
      distributed and may eventually become consolidated in the neocortex.

PMID- 9276844
TI  - Neuropsychiatric symptoms from the temporolimbic lobes.
AB  - Neuropsychiatric symptoms are common manifestations of temporolimbic lesions.
      These neuropsychiatric symptoms result from disturbances of specific
      temporolimbic networks, including medial limbic circuits, lateral limbic
      circuits, and the "extended" amygdala. Moreover, temporolimbic networks interface
      with multiple cortical and subcortical circuits that modulate emotional behavior
      and affect. This article not only reviews these behaviorally relevant aspects of
      temporolimbic neuroanatomy, but also describes positive, productive symptoms from
      the temporal lobes. The Kluver-Bucy syndrome, the Gastaut-Geschwind syndrome,
      emotional or mood disorders, delusions, anxiety and associative disorders, and
      neurovegetative symptoms are discussed, as well as amnesia, the signature
      temporolimbic disturbance of cognition. The temporolimbic lobe is a classic
      example of a widely distributed circuit within the brain that has behaviorally
      relevant manifestations.

PMID- 9276845
TI  - The neurobiology of emotional experience.
AB  - The author discusses a neurological model of a modular network that mediates
      emotional experience. According to this theory, emotional experience has three
      components: valence (positive and negative), arousal, and motor activation
      (approach, avoid, neither). In this model, the cortex is critical in regulating
      activities of the limbic system, basal ganglia, and reticular system. The frontal
      lobes are important for valence: the left mediates positive emotions, the right
      negative emotions. The right hemisphere, especially the parietal lobe, is
      important in activating arousal systems, and the left hemisphere modulates
      inhibition of these systems. The right hemisphere is also critical in motor
      activation. The frontal lobes, especially the orbitofrontal portions, mediate
      avoidance behaviors, and the parietal lobes mediate approach behaviors. The
      cortical areas discussed have rich interconnections and are also closely
      connected with the limbic system, basal ganglia, and reticular systems. Emotional
      experience may depend on the patterns of neural activation in this modular
      network.

PMID- 9276846
TI  - The neurobiology of recovery memory.
AB  - The so-called recovery memory syndrome--reports by adults of recovered memories
      of childhood sexual abuse and trauma that were allegedly "repressed" for many
      years--has become an important issue in the field of mental health. In
      particular, there is debate about the credibility of recovered memories. The
      author describes findings in several fields of brain science about the way memory
      works and how memory is organized in the brain. These findings clarify aspects of
      normal memory function and the process of memory distortion, and they provide a
      neurobiological perspective from which to approach the topic of recovered memory.

PMID- 9276847
TI  - The medial temporal lobe in schizophrenia.
AB  - Evidence from diverse avenues of research has highlighted abnormalities in the
      anatomy, physiology, and function of medial temporal lobe structures in
      schizophrenia. Clinical similarities between schizophrenia and psychotic
      disorders associated with temporal lobe lesions have been recognized for decades.
      Neuropsychological studies have found selective impairments in learning and
      memory in schizophrenia consistent with medial temporal lobe dysfunction.
      Neuroimaging studies have identified medial temporal lobe abnormalities that have
      been correlated with clinical features. Postmortem findings in the hippocampus
      and entorhinal cortex have included differences in neuron density, size, and
      arrangement; abnormalities in synapse-related proteins; alterations in
      monoaminergic and glutamatergic innervation and receptor distribution; and
      abnormalities in the expression of cytoskeletal proteins. These findings appear
      most consistent with models of aberrant development of medial temporal lobe
      structures in schizophrenia.

PMID- 9276848
TI  - Limbic-cortical dysregulation: a proposed model of depression.
AB  - A working model of depression implicating failure of the coordinated interactions
      of a distributed network of limbic-cortical pathways is proposed. Resting state
      patterns of regional glucose metabolism in idiopathic depressed patients, changes
      in metabolism with antidepressant treatment, and blood flow changes with induced
      sadness in healthy subjects were used to test and refine this hypothesis. Dorsal
      neocortical decreases and ventral paralimbic increases characterize both healthy
      sadness and depressive illness; concurrent inhibition of overactive paralimbic
      regions and normalization of hypofunctioning dorsal cortical sites characterize
      disease remission. Normal functioning of the rostral anterior cingulate, with its
      direct connections to these dorsal and ventral areas, is postulated to be
      additionally required for the observed reciprocal compensatory changes, since
      pretreatment metabolism in this region uniquely predicts antidepressant treatment
      response. This model is offered as an adaptable framework to facilitate continued
      integration of clinical imaging findings with complementary neuroanatomical,
      neurochemical, and electrophysiological studies in the investigation of the
      pathogenesis of affective disorders.

PMID- 9276849
TI  - The neurobiology of drug addiction.
AB  - Animals models have begun to provide insights into the neurobiological basis of
      reinforcement in drug addiction. The reinforcing effects of indirect
      sympathomimetics such as cocaine and amphetamine appear to depend on release of
      dopamine in the terminal fields of the mesocorticolimbic dopamine system. The
      acute reinforcing effects of opiates involve not only an activation of dopamine,
      but also dopamine-independent elements in the terminal regions of the
      mesocorticolimbic dopamine system. Nicotine's reinforcing effects may involve
      both dopaminergic and opioid peptidergic systems. Ethanol's reinforcing effects
      may result from multiple neurotransmitter interactions including gamma
      aminobutyric acid, glutamate, dopamine, opioid peptides, and serotonin. Subtle
      changes in neurochemical function and signal transduction and transcription
      mechanisms in sensitive neuronal elements in the extended amygdala may be
      mediators of chronic drug action that lead to vulnerability to relapse and may
      provide exciting insight into the neuroadaptations associated with drug
      addiction.

PMID- 9276850
TI  - The neural substrates of religious experience.
AB  - Religious experience is brain-based, like all human experience. Clues to the
      neural substrates of religious-numinous experience may be gleaned from
      temporolimbic epilepsy, near-death experiences, and hallucinogen ingestion. These
      brain disorders and conditions may produce depersonalization, derealization,
      ecstasy, a sense of timelessness and spacelessness, and other experiences that
      foster religious-numinous interpretation. Religious delusions are an important
      subtype of delusional experience in schizophrenia, and mood-congruent religious
      delusions are a feature of mania and depression. The authors suggest a limbic
      marker hypothesis for religious-mystical experience. The temporolimbic system
      tags certain encounters with external or internal stimuli as depersonalized,
      derealized, crucially important, harmonious, and/or joyous, prompting
      comprehension of these experiences within a religious framework.

PMID- 9276852
TI  - Burnout in orthopaedic physical therapists.
AB  - Few studies exist about burnout in physical therapists. No research is available
      on burnout in orthopaedic therapists. The purpose of this study was to determine
      if burnout exists in this group and if a relationship exists between burnout
      scores and selected variables. Members of the Orthopaedic Section of the American
      Physical Therapy Association from the east north central region of the United
      States were sent a survey consisting of demographic questions and the Maslach
      Burnout Inventory. The return rate was 38.7%. Burnout levels were low to moderate
      depending on the grouping used to examine the data. All of the variables examined
      (eg., years as a physical therapist, number of patients seen per day) showed very
      low correlations with subscale scores. Further research is needed to identify
      those at most risk for burnout and to find effective strategies for its
      prevention.

PMID- 9276853
TI  - The effects of heating with ultrasound on knee joint displacement.
AB  - Heating with continuous wattage ultrasound combined with mobilization procedures
      is often used to treat ligament "tightness," but the effects of heat on ligament
      extensibility have not previously been studied in vivo. To address this problem,
      25 young adults underwent knee joint displacement tests on a Genucom arthrometer
      before and after continuous wattage ultrasound (1 MHZ, 1.5 W/cm2 x 8 min).
      Preultrasound intrarater reliability (ICC; N = 11) was 0.87-0.98 for varus/valgus
      and recurvatum tests and 0.70-0.73 for anterior-posterior drawer tests. RESULTS:
      Continuous wattage ultrasound was associated with small increases in mean
      varus/valgus excursion at 0 degree and 20 degrees of knee flexion (p < or = .04)
      and in recurvatum excursion (p < or = .04) but not in anterior-posterior drawer
      excursion. The magnitude of the changes was 1.3 degrees or less and represented
      relative changes of 6.1-9.8%. CONCLUSION: Continuous wattage ultrasound at common
      clinical intensities made some knee ligaments slightly more extensible in normal
      subjects, although the magnitude of the effect was not deemed clinically
      significant.

PMID- 9276854
TI  - Reliability of lower extremity functional performance tests.
AB  - Clinicians routinely have used functional performance tests as an evaluation tool
      in deciding when an athlete can safely return to unrestricted sporting
      activities. These practitioners assumed that these tests provide a reliable
      measure of lower extremity performance; however, little research has been
      reported on the reliability of these measures. The purpose of this investigation
      was to determine the reliability of lower extremity functional performance tests.
      Five male and 15 female volunteers were evaluated using the single hop for
      distance, triple hop for distance, 6-m timed hop, and cross-over hop for distance
      as described by Noyes (10). One clinician measured each subject's performance
      using a standardized protocol and retested subjects in the same manner
      approximately 48 hours later. The order of testing was randomly determined.
      Subjects' average and individual scores on each functional performance test were
      used for statistical analysis. Intraclass correlation coefficients (ICCs) and
      standard error of measurement (SEM) values based on average day 1 and day 2
      scores were used to estimate the reliability of each functional performance test.
      Intraclass correlation coefficients were .96, .95, and .96, and SEMs were 4.56
      cm, 15.44 cm, and 15.95 cm, respectively, for the single hop, triple hop, and
      cross-over hop for distance tests. An ICC of .66 and SEM of .13 seconds for the 6
      m timed hop resulted from limited variability between measurements; however, its
      small SEM value inferred that the inconsistency of measurement would occur in an
      acceptably small range. A repeated measures analysis of variance revealed no
      significant difference ( p > .05) between individual trial scores except for the
      single hop for distance. We concluded that this difference represented a learning
      effect not found with the other tests. The results of this investigation
      demonstrate that clinicians can use functional performance testing to obtain
      reliable measures of lower extremity performance when using a standardized
      protocol.

PMID- 9276855
TI  - Relationship between isokinetic concentric and eccentric contraction modes in the
      knee flexor and extensor muscle groups.
AB  - We investigated whether in normal subjects isokinetic concentric and eccentric
      strength variables were related in order to have a better picture in relation to
      rehabilitation and possible injury prevention. We studied the relationship
      between isokinetic concentric and eccentric peak torque, total work, and average
      power of knee extension and knee flexion at 60 degrees/sec and 120 degrees/sec in
      42 young Chinese adults (22 males, age = 27 +/- 6.9 years; 20 females, age = 24.9
      +/- 5.05 years) using the Cybex 6000 isokinetic dynamometer. Repeated analysis of
      covariance was used to compare the means between concentric and eccentric
      variables adjusted by limb dominance, speed of testing, and the muscle groups
      tested. A highly significant correlation was found between all concentric and
      eccentric variables, with correlation coefficients (r) ranging from 0.67 to 0.93.
      All but two of the eccentric variables were significantly greater than the
      concentric variables. Concentric and eccentric knee flexion to knee extension
      (H:Q) ratios were poorly correlated, with r ranging from 0.359 to 0.645. Although
      there is an acceptably high correlation between isokinetic concentric and
      eccentric strength variables of knee flexion and extension in young healthy
      individuals, we recommend measuring concentric and eccentric strength to plan a
      proper rehabilitation program and to assess muscle groups in a given contraction
      mode.

PMID- 9276856
TI  - The isokinetic torque curve of shoulder instability in high school baseball
      pitchers.
AB  - Athletes with shoulder problems are commonly referred to orthopaedic and sports
      physical therapists for rehabilitation. Many of these problems include some form
      of shoulder instability. The purpose of this study was to generate an isokinetic
      torque curve that is representative of the shoulder impingement syndrome that may
      affect high school baseball pitchers. A sample of 241 subjects, each diagnosed
      with an impingement syndrome in the right shoulder, was tested using a Cybex II+
      dynamometer configured to duplicate the orthopaedic loose-packed and plane of the
      scapula positions of the shoulder complex. The subjects were tested
      concentrically across five maximal repetitions of internal and external rotation
      at the speeds of 60, 120, 180, 240, and 300 degree/sec; graphic records were
      collected at 60 degrees/sec. Descriptively, testing revealed a distinct
      isokinetic torque curve for the impingement syndrome compared with the
      noninvolved shoulder. This information might serve as a useful complement to
      traditional clinical procedures for the diagnosis of the shoulder impingement
      syndrome.

PMID- 9276857
TI  - A three-paradigm treatment model using soft tissue mobilization and guided
      movement-awareness techniques for a patient with chronic low back pain: a case
      study.
AB  - It is not uncommon for physical therapists to report difficulty in treating
      certain subjects with chronic idiopathic low back pain. The purpose of this case
      study is to present a three-paradigm model of intervention that may be adapted to
      the treatment of such cases. The model consists of: 1) relaxation paradigm,
      consisting of pain modulation procedures; 2) corrective paradigm, involving
      manual techniques and exercise to correct specific faulty biomechanical
      alignment(s) eg., pelvic asymmetry); and 3) integrative paradigm, utilizing
      guided movement/mobilization techniques for improving the subject's overall
      pattern of posture and movement. The case study of a young adult with chronic low
      back pain correlated with unilateral innominate bone rotation is presented to
      illustrate the three-paradigm approach. Over six sessions, the subject received a
      corrective (sessions 1-3) and an integrative treatment protocol (sessions 4-6)
      consisting of Rolf's method of soft tissue mobilization and Alexander's system of
      guided movement-awareness techniques. Before and after each session and after a 4
      week follow-up, the subject was assessed for sacroiliac joint pain using a
      compression technique, anterior rotation of the innominate bones, pelvic angle in
      the standing position, and vagal tone as determined from heart rate variability.
      The therapist's visual analysis of sit-to-stand movement and the subject's self
      reports of pain were noted. A corrective paradigm protocol of soft tissue
      mobilization and exercise was unsuccessful in eliminating the subject's assessed
      anterior rotation of the innominate bone and associated low back pain for more
      than 1-2 days posttreatment. Only after the implementation of a third paradigm
      movement/mobilization protocol did the subject begin to exhibit sustained
      improvement through a 4-week follow-up. Interpretations of the results,
      appropriate selection of corrective and integrative protocols, and physiological
      mechanisms are discussed.

PMID- 9276858
TI  - Patella fractures associated with accelerated ACL rehabilitation in patients with
      autogenous patella tendon reconstructions.
AB  - Patella fracture is a recognized complication of ACL reconstruction with an
      autogenous patella tendon graft. Typically, fracture occurs as a result of a
      fall. The incidence of fracture is approximately 0.5%. Accelerated rehabilitation
      protocols can place stress on the patella, especially in the initial stages of
      recovery. Therapists are reminded to observe constraints placed on patients by
      biological tissues, recovering neuromuscular status, and previous level of
      conditioning. Rehabilitation protocols should be revised according to these
      factors.

PMID- 9276859
TI  - European Stroke Prevention Study 2. Efficacy and safety data.

PMID- 9276860
TI  - Antiarrhythmic agents: current status and perspectives.

PMID- 9276861
TI  - How design statistics concepts can improve experimentation in medicinal
      chemistry.

PMID- 9276862
TI  - The metabolic basis of cancer cachexia.

PMID- 9276864
TI  - [Detection and prognosis of small pancreatic ductal adenocarcinoma].
AB  - Symptoms and laboratory studies provide only limited assistance in the screening
      of small pancreatic carcinomas. Ultrasound and CT are best suited for screening
      small pancreatic carcinomas because of their ease and accuracy. When ultrasound
      and CT findings suggest small pancreatic carcinomas, MR cholangiopancreatography
      and endoscopic ultrasound should be indicated. Both techniques can show very
      small tumors noninvasively. Follow-up of 79 patients with pancreatic carcinoma in
      whom the tumor was resected showed that 5-year survival rate of patients with
      tumor limited to the duct epithelium was 100%. Majority of these tumors were
      smaller than 1 cm. These tumors are considered early pancreatic carcinoma.

PMID- 9276863
TI  - [The results of treatment for pancreatic cancer--statistic change].
AB  - Between 1981 and 1995, 17, 121 patients with pancreatic cancer were registered by
      Japan Pancreas Society (JPS). The resection rate was 36.1% with recent increase.
      The 1, 3, and 5 year actuarial survival rates of resected cases were 52.7%,
      24.0%, and 18.6%, respectively. As for resectional procedures, there was a
      gradual decrease in TP and increase in PD. Lymph node metastases are found in
      37.0% of patients with tumor size less than 2 cm, therefore, and extended
      lymphadenectomy and extended surgery including portal vein resection are more
      performed than before in Japan. Tubular adenocarcinoma are 60.6% in all
      registered pancreatic cancer, but its survival rate is only 10%. The survival
      rate of the National Cancer Data Base was almost the same as that of us with
      higher resection rate, but we cannot easily accepted its fact as the background
      of patients are various.

PMID- 9276865
TI  - [Molecular diagnosis of pancreatic cancer].
AB  - Genetic alterations such as K-ras mutation, inactivation of the p53, p16 and DPC4
      genes and frequent chromosomal loss of the 17p, 9p, 18q and 1p are thought to
      play a crucial role in the carcinogenesis of pancreatic cancer. Mutations of K
      ras oncogene could be detected frequently in pancreatic juice samples from
      patients with pancreatic carcinoma and intraductal papillary neoplasm (IPN),
      although they could be detected in some of the samples from patients with chronic
      pancreatitis and pancreatic cyst. This suggests that K-ras mutation is an early
      event in the carcinogenesis of the exocine pancreas. In IPN, analysis of other
      genetic alteration would be available, since pancreatic juice samples from the
      patient are relatively rich in the proportion of the tumor cells. A new
      diagnostic modality of sensitive allelotyping would be useful for evaluating
      malignant potential of these borderline lesions.

PMID- 9276866
TI  - [Diagnosis of tumor extension of ductal adenocarcinoma of the pancreas based on
      histological findings].
AB  - This study was undertaken to evaluate the diagnosis for tumor extension of ductal
      adenocarcinoma of the head of the pancreas based on histological investigation.
      From 1968 to 1995, 316 patients underwent radical resection and histological
      tumor extension was quite as follows; the rate of invasion to the anterior
      pancreatic capsule was 49%, invasion to the retroperitoneal tissue was 77%,
      invasion to the portal vein system was 38%, invasion to the extrapancreatic nerve
      plexus was 53% and lymph node metastases were 79%. 249 patients was performed
      extended radical operation consisted of regional lymphadenectomy, retroperitoneal
      dissection and resection of portal vein system, however non-curative resection
      was 52% with tumor invasion to dissected pancreatic surface in 88% of non
      curative patients. And there was no 5-year survivor with non-curative resection.
      The extended radical operation should be indicated for patients who will have
      curative resection. Then, we set up clinical stage (CS; CSI approximately IV) by
      three factors related to resectability mostly; invasion to retroperitoneal tissue
      (RP), invasion to portal vein system (PV), invasion to major arterial system (A).
      It was also set up preoperative diagnostic criteria for RP, PV and A factor by
      computed tomography (CT) or abdominal angiography. From 1989 to 1995, 101
      patients who had extended radical operation were investigated prospectively. The
      rate of accuracy of preoperative diagnosis of tumor extension were about 80% in
      each factor. Curability was 94% in CS I, 67% in CS II, 43% in CS III,
      respectively, and 3-year survival rate was 53% in CS I, 35% in CS II, 2-year
      survival rate was 8% in CS III. However, in CS IV the rate of non-curative
      resection was 77% and there was no 2-year survivor. It was concluded that
      extended radical operation of ductal adenocarcinoma of the head of the pancreas
      should be indicated for patients in less than CS III diagnosed by CT or
      angiography preoperatively.

PMID- 9276867
TI  - [Changes in lymph node dissection for pancreatic cancer].
AB  - Two step pancreatoduodenectomy for periampullary carcinoma was first reported in
      1912 by Kausch. Pancreatoduodenectomy performed for carcinoma of the head of the
      pancreas was first reported in 1937 by Brunschwig. Before this report, all
      previous pancreatoduodenectomy had been performed for other periampullary tumors.
      By the 1960's, pancreatoduodenectomy was performed for pancreatic cancer without
      lymph node dissection. However, Fortner advocated regional pancreatectomy for
      pancreatic cancer in 1973. In our institute, also, extended radical
      pancreatectomy by translateral retroperitoneal approach has been performed during
      the past 2 decades. Many Japanese surgeons also adopted extend pancreatectomy. In
      the 1980's, extended radical pancreatectomy consisted of paraaortic lymph node
      dissection, total pancreatectomy, and complete resection of extrapancreatic nerve
      plexus. However, based on the many clinicopathologic studies,
      pancreatoduodenectomy was better operative procedure than total pancreatectomy.
      Although extended radical pancreatectomy has the advantage of long-time survival,
      disadvantage of nutritional status and quality of life was produced by this
      operative procedure. Tarverso and Longmire reported new operative procedure of
      pylorus preserving pancreatoduodenectomy (PPPD) in 1978. Recently, this operative
      procedure was indicated for pancreatic cancer. However, there is a question
      whether PPPD is the best operative procedure for pancreatic cancer or not.

PMID- 9276868
TI  - [Indication and results of pancreatectomy with combined resection of vessels for
      adenocarcinoma of the pancreas].
AB  - Of 192 patients who received pancreatectomy for invasive adenocarcinoma of the
      pancreas, 107 (55. 7%) underwent combined resection of vessels at Keio University
      Hospital and Tochigi Cancer Center, from July 1974 until March 1996. Vascular
      resections included the portal and/or mesenteric vein in 103, the common hepatic
      artery in 14, the superior artery in 2 and the celiac axis in 5 cases. The
      morbidity and mortality rate are 20.2%, 1.2% in the standard resected group and
      23.1%, 5.6% in the vessel resected group, respectively. Comparison of the
      survival rate of curability A and B patients between two groups shows no
      significant difference. Six patients who underwent resection of the portal and/or
      mesenteric vein survived more than 5 years. The longest survivor is living 13
      years 6 months after surgery. Among the patients who underwent resection of the
      artery, two patients survived 44 and 22 months after distal pancreatectomy with
      resection of the celiac axis and the common hepatic artery preserving whole
      stomach.

PMID- 9276869
TI  - [Pancreatic anastomosis after pancreatoduodenectomy].
AB  - Leakage from a pancreatic anastomosis after a pancreatoduodenectomy is one of the
      serious problems that can bring on life-threatening complications and lead to
      operative mortality. To minimize these complications, various reconstruction
      methods have been proposed. A series of 183 patients underwent
      pancreatoduodenectomy between August 1981 and December 1996 at 1st Department of
      Surgery, Teikyo University School of Medicine. Our pancreatic anastomoses were
      classified into four groups based on "Classification of Pancreatic Carcinoma
      (Japan Pancreas Society, FirstEnglish Edition, Kanehara, Tokyo 1996)",: (a)
      mucosa-to-mucosa pancreatico jejunostomy in 58 cases, (b) tube assisted
      (telescoped typed) pancreaticojejunostomyin 104, (c) pancreaticojejunostomy
      through dunking method in 2, and (d) panc reaticogastrostomy in 19. The leakage
      occured in 5 out of 104 of tube-assisted pancreaticojejunostomy, in 1 out of 19
      of pancreaticogastrostomy. Due to the smooth healing process of anastomosis,
      mucosa-to-mucosa pancreaticojejunostomy have been applied, leading to results
      were no leakage occurred in 58 consecutive cases.

PMID- 9276870
TI  - [Intraoperative radiotherapy combined with extended resection for pancreatic
      cancer].
AB  - Since 1984, intraoperative radiotherapy combined with extended resection for
      pancreatic cancer has been performed in our clinic to prevent local recurrence.
      Following extended resection, a dose of 30 Gy of 9-12 MeV electrons was
      administered to the operative field including the paraaortic area from the
      diaphragm above to the inferior mesenteric artery below. Results of the combined
      therapy of 35 patients were compared to results of 11 patients who underwent
      extended resection alone. The combined therapy group compared to extended
      resection alone group showed improvement in the survival rate. It's 5 year
      survival rate was 16.8% in all the 35 cases, 22.3% in patients who had
      macroscopic tumor clearance and 18.9% in patients with Stage IVa tumour according
      to The Japanese classification. In autopsies of 10 cases who underwent the
      combined therapy, only 4 had local recurrence enclosed by thick, firm connective
      tissue. There was no any local recurrence in 2 cases who underwent non curative
      resection. Enhanced local control induced by the combined therapy, however, only
      has a limited impact on overall survival, because of system disease progression,
      especially hepatic metastases. These results suggest that combination of IORT and
      extended resection should be performed on selected patients to control local
      recurrence and anticancer treatment for metastases of the liver must be
      established for the cure of pancreatic cancer as soon as possible.

PMID- 9276871
TI  - [Chemotherapy for adenocarcinoma of the pancreas].
AB  - The present article reviews previous reports on the systemic and regional
      chemotherapies for adenocarcinoma of the pancreas. When non-resectable pancreatic
      cancer was treated by the systemic chemotherapy, most reports showed that the
      mean or median survival periods were less than 6 months. Although the response
      rate to multi-drug chemotherapy was superior than that to single-drug
      chemotherapy, the survival period did net differ significantly between the two.
      In general, in terms of the patients, survival rates, the combination og chemo
      therapy and radiation was slightly superior to either chemotherapy or radiation
      alone. On the other hand, regional chemotherapy seems to be more promising
      because our intra-arterial chemotherapy using angiontensin-II has succeeded in
      improving the mean survival period to 14 months for non-resectable pancreatic
      cancer. Likewise, liver perfusion chemotherapy via the hepatic artery and portal
      vein was effective in preventing the development of liver metastasis after
      pancreatectomy. Considering that the pancreatic cancer is a poorly vascularized
      tumor, it is essential to deliver a high dose of anti-cancer drug effectively
      into the cancer tissue. Secondarily, the selection of drug to which the
      pancreatic cancer cell is sensitive is also important.

PMID- 9276872
TI  - [Newly-developing therapies of pancreatic cancer--immunotherapy, gene therapy,
      differentiation therapy, endocrine therapy and others].
AB  - Pancreatic cancer is extremely resistant to various cancer therapies, however,
      variety of new therapies for pancreatic cancer have been investigated: (1)
      immunotherapy including cytokines like TNF, adoptive immunotherapy with
      lymphokine-activated killer cells or cytotoxic T-lymphocytes, and tumor vaccines
      using mutated Ki-ras oncoprotein or irradiated tumor cells which were transfected
      by cytokine genes; (2) gene therapy including transfer of cytokine genes or
      antisense Ki-ras oncogene, and a combination of gene transfer of herpes simplex
      virus thymidine kinase and subsequent administration of ganciclovir; (3)
      differentiation therapy including a quinolinone derivative, vesnarinone; (4)
      endocrine therapy including cholecystokinin-receptor antagonist, CR1505 or
      L364,718; (5) heavy water, and etc. All of these therapies will be applied for
      the treatment of pancreatic cancer in the near future.

PMID- 9276873
TI  - [Perineural invasion and surgical treatment of the pancreas head cancer].
AB  - It is thought that perineural invasion by pancreatic cancer takes place either by
      means of direct tumor invasion of the perineural space or by means of tumor
      invasion through the vessels perforating the perineurium. The manner of tumor
      progression may be divided into four types: (1) direct progression of cancer
      cells into the perineural space, (2) branching at the bifurcation of the nerve
      fascicle, (3) perineural invasion by a probing cancer tip, and (4) invasion
      beyond the perineurium through defects in it. Because pancreatic cancer is often
      followed by severe tumor invasion of surrounding organs, major blood vessels and
      extrapancreatic plexus, the survival rate after the conventional
      pancreatoduodenectomy has been unsatisfactory. Since 1977, the author has used
      extended pancreatectomy with a trans-lateral retroperitoneal approach, involving
      resection of the portal vein, extensive excision of the retroperitoneal lymph
      nodes and complete resection of the pancreatic head plexus. After this surgery,
      11 patients survived for more than 3 years. The five-year survival rate was 25%
      in case where this operation was rated as being a macroscopic curative resection.

PMID- 9276874
TI  - [Surgical treatment and research of esophageal cancer in the past and the present
      era in our department--for the view point of the future].
AB  - We describe the result of esophageal cancer treatment in the past era of the
      Department of Surgery, Chiba University School of Medicine directed by Professor
      Seo, Nakayama and Sato and the improved results of the treatment at the present
      time from the view point of diagnosis (early superficial cancer, lymph node
      metastasis and adjacent organ invasion) and treatment (three-field lymph node
      dissection, improved result of operative mortality and morbidity, improvement of
      long-term survival rate). In addition, we prospect the future through the present
      study such as mutation of P53 gene and malignancy, immunotherapy using cytokine
      gene transfer, cancer inhibition therapy by induction of cancer suppressor gene,
      prodrug therapy, heavy particle iron therapy, and clinical application of virtual
      reality to the surgical field.

PMID- 9276875
TI  - [Crush syndrome].

PMID- 9276876
TI  - [New aspects of human cancer immunology].

PMID- 9276877
TI  - [Kienbock disease--result of our treatment and biomechanical study].

PMID- 9276878
TI  - Responses of meat-type chickens to choice feeding of diets differing in protein
      and energy from hatch to market weight.
AB  - Chickens from three genetic stocks known to differ in growth potential consumed
      ad libitum either a single (control) diet or a choice of two diets that differed
      in protein and energy. Formulation of the choice diets was such that when mixed
      in specific proportions they provided single diets that decreased in protein and
      increased in energy over the experimental period. When comparisons of feeding
      regimens were made at a common age, body weights and feed efficiencies for all
      stocks were enhanced in chicks fed a single diet. When comparisons were made at a
      common body weight for controls, chickens fed the single diet were about 15%
      heavier than those given a dietary choice. For feed efficiency, however, the
      pattern remained for the faster growing stock whereas there was no difference
      between feeding regimens for the slower growing stock. Chicks provided a choice
      of diets had heavier abdominal fat pads and lighter breasts relative to body
      weight than those fed a single diet. With choice feeding, there were stock by
      diet interactions for dietary preferences through the first 9 d after hatch.
      Early on, the interactions resulted from the faster growing stocks exhibiting a
      greater preference for the diet higher in protein and lower in energy than the
      slower growing stock. By Day 5, however, the interaction occurred because stocks
      exhibited either no dietary preference or preferred the diet that was lower in
      protein and higher in energy. Regardless of genetic stock, at 9 d of age and
      thereafter there was a clear preference for the diet lower in protein and higher
      in energy than the diet higher in protein and lower in energy. These data for
      feed intake were consistent with behavioral observations that showed a
      preponderance of chicks eating from the feeder containing the diet lower in
      protein and higher in energy. Compared to a single diet, under choice feeding,
      energy utilization was negatively influenced more in the faster than slower
      growing stocks. Protein and sulfur amino acid utilization was not affected by
      feeding regimen in faster growing stocks, but was enhanced under choice feeding
      in the slower growing stock. Although lysine utilization was enhanced by choice
      feeding in all stocks, the effect was greater in the slower than in the faster
      growing ones. These data demonstrate that although broiler diets are formulated
      to enhance growth and overall feed efficiency, chicks that are provided a dietary
      choice of protein and energy do not eat to maximize growth or feed efficiency.

PMID- 9276880
TI  - Carcass traits and reproductive development at the onset of lay in two lines of
      female turkeys.
AB  - A study was conducted comparing ovary and oviduct development following
      photostimulation in two lines of turkey breeder stocks (female line and male
      line). Birds were euthanatized for assessment of reproductive organ morphology at
      3-d intervals following photostimulation (203 d of age) to 245 d and on the day
      following their first oviposition. The age at first oviposition was similar for
      both lines. Male line birds were 3 to 4 kg heavier than female line birds
      throughout the study, but had lower abdominal fat pad weights when expressed as a
      percentage of BW. Female line birds had significantly more total carcass lipid as
      a percentage of BW than male line birds (24.76 vs 22.79%, respectively). Male
      line birds had significantly more large ovarian follicles with a greater
      proportion in a triple or greater hierarchical arrangement at first egg. To
      determine the incidence of unreconciled ovulations (presumed to be internally
      ovulated follicles and defined as ovulations occurring prior to first
      oviposition), postovulatory follicles on the ovary were reconciled with observed
      ovipositions and the developing eggs that were in the oviduct at the time of
      study. On average, male line hens had 3.0 unreconciled postovulatory follicles at
      first egg, whereas the female line hens had 1.6. The incidence of birds with
      physical remnants of internal ovulation was correlated (r = 0.44) to the number
      of unreconciled ovulations. The developing oviduct of the female line birds
      reached its mature weight (84.8 g) 3 d earlier than the ovary did. The developing
      ovary and oviduct of the male line hens reached their mature weights on the same
      day. The development of the male line oviduct is seemingly accelerated relative
      to that of the ovary, resulting in lost ovulations early in lay.

PMID- 9276879
TI  - Genetic parameters of survival to the different stages of embryonic death in
      laying hens.
AB  - Heritabilities and genetic correlations of fertility (FERT) as well as of
      susceptibilities to early (EEM), medium (MEM), and late (LEM) embryonic
      mortalities conditional on fertility and survival to earlier stage(s) of
      embryonic mortality were estimated with a general linear model using a logistic
      link function on 59,794 eggs obtained from 6,480 hens issued from 228 sires and
      1,053 dams. Estimated heritabilities of FERT, EEM, MEM, and LEM were, when
      estimated from sire and dam components, respectively, equal to 0.09 and 0.31,
      0.09 and 0.25, 0.07 and 0.20, and 0.05 and 0.18; whereas estimated heritabilities
      of hatchability of fertile eggs were 0.05 and 0.15, respectively, when estimated
      from the sire or dam components. Most genetic correlations between FERT, EEM,
      MEM, and LEM were favorable with the exception of correlations between FERT and
      MEM and between EEM and MEM when estimated from the sire component. These results
      show the theoretical interest of distinguishing the three stages of mortality.

PMID- 9276881
TI  - Influence of a superactivated charcoal on the toxic effects of aflatoxin or T-2
      toxin in growing broilers.
AB  - To evaluate the effectiveness of a superactivated charcoal (SAC) in alleviating
      mycotoxicosis, two experiments were conducted in which 432 male broiler chicks
      (216 per experiment) were fed diets containing 4 mg aflatoxin (AF) or 6 mg T-2
      toxin/kg of diet, with and without 0.5% SAC, from 1 to 21 d of age. Feeding AF
      and T-2 toxin significantly decreased BW gain over the 21-d experimental period.
      Inclusion of SAC in the diet containing AF resulted in BW gains that were
      intermediate between gains of chicks fed AF and those of controls. No benefits
      were seen in BW gain when SAC + T-2 toxin was fed. Feeding AF increased relative
      weights of liver, spleen, and kidney; however, only liver weight in Experiment 1
      was similar to controls when SAC was included. Of the blood parameters altered by
      AF (decreased cholesterol, inorganic phosphorus, total protein, and urea
      nitrogen, and increased mean corpuscular volume and hematocrit in Experiment 1;
      decreased albumin and total protein, and increased creatine kinase in Experiment
      2) only urea nitrogen, hematocrit, and inorganic phosphorus (Experiment 1) and
      hematocrit (Experiment 2) were comparable to controls when SAC was included in
      the diet. Feeding T-2 toxin decreased serum cholesterol, total protein, urea
      nitrogen, and mean corpuscular volume; however, only cholesterol and mean
      corpuscular volume were improved with the addition of SAC (Experiment 1). Oral
      lesions were observed in birds fed T-2 toxin with no difference in severity when
      SAC was added in Experiment 1, however in Experiment 2, birds fed SAC + T-2 had a
      significantly lower lesion scores than those fed T-2 alone. Mortality was noted
      in both experiments but was not influenced by SAC treatment. These findings
      suggest that the addition of dietary SAC is marginally effective in alleviating
      some of the toxic affects associated with AF, but was of little benefit when T-2
      toxin was fed to growing broiler chicks.

PMID- 9276882
TI  - Preservation of hatchery waste by lactic acid fermentation. 1. Laboratory scale
      fermentation.
AB  - In Experiment 1, two types of hatchery wastes, including cockerel chicks (CC),
      and shell waste (SW) blended with CC (60:40 CC:SW), were ground and mixed with a
      by-product carbohydrate (5, 10, and 15% wt/wt) with or without a bacterial
      culture and fermented for a period of 21 d. Cockerel chicks fermented with 15%
      carbohydrate and the culture had a pleasant smell and little H2S production.
      Elevated H2S concentrations were recorded for CC:SW samples at all carbohydrate
      levels when the culture was not added. No NH3 was detected from any treatments
      during fermentation. The addition of culture to the CC and CC:SW by-products
      resulted in pH values lower (P < 0.05) than those without culture on Day 21, and
      the 15% carbohydrate treatment significantly reduced pH beyond the 5%
      carbohydrate. Final proximate composition of CC and CC:SW samples with culture
      were not significantly different from those without culture added. In Experiment
      2, carbohydrate was added at 10.0, 13.3, 16.7, and 20.0% wt/wt to CC and CC:SW in
      the presence of the bacterial culture. Shell waste alone was fermented with 15,
      20, and 25% carbohydrate and the culture. Moisture level in this experiment was
      adjusted to approximately 70% for all treatments. The lowest pH for the CC and
      CC:SW treatments was observed at the 16.7% carbohydrate level. Shell waste pH was
      better maintained at the 20 and 25% carbohydrate levels. After fermentation for
      21 d CC, CC:SW and SW treatments from Experiments 1 and 2 contained negligible
      Escherichia coli, and no Salmonella were detected.

PMID- 9276883
TI  - Preservation of hatchery waste by lactic acid fermentation. 2. Large-scale
      fermentation and feeding trial to evaluate feeding value.
AB  - Two waste streams from a Leghorn hatchery were preserved and recycled by
      fermentation with a by-product carbohydrate and extrusion processing into new
      feed ingredients that were evaluated with broiler chickens. Cockerel chicks (CC)
      and a 60:40 ratio of CC:shell waste (CC:SW) were fermented in 189-L barrels for
      21 d following grinding, then mixing with a liquid culture (0.2%) and
      carbohydrate source at 15 and 16.66%, respectively. At 2 wk, pH was 4.44 and 5.09
      for the CC and CC:SW products compared with higher values of 6.54 and 6.98 for
      the raw ingredients at the onset. Negligible hydrogen sulfide and no ammonia gas
      were recorded during the fermentation period. At 21 d, the fermented CC and CC:SW
      were extruded, dried, and ground to meals containing CP and TMEn levels of 47.4%,
      3,187 kcal/kg, and 33.1%, 2,696 kcal/kg, respectively. Broiler chickens were fed
      a control diet and the CC (5 and 10%) and CC:SW (2.5 and 5%) ingredient diets
      with corn and soybean meal for 6 wk to evaluate feeding value and carcass yield.
      Body weight, gain and feed conversion at 42 d for birds fed diets supplemented
      with CC or CC:SW at all levels were comparable to those of the control. Diets
      supplemented with hatchery by-product had no negative effect on carcass
      measurements except ready to cook carcass and wing yield, which were
      significantly greater for the 10% CC:SW birds than for the control. These data
      indicate that nutrient dense hatchery by-products can be preserved with
      fermentation up to 21 d and support broiler live performance and carcass yield as
      dietary ingredients equal to or better than a corn-soybean meal control.

PMID- 9276884
TI  - Yeast treatment to reduce Salmonella and Campylobacter populations associated
      with broiler chickens subjected to transport stress.
AB  - The prevalence of Campylobacter and Salmonella on retail poultry carcasses
      remains a significant public health concern. The stresses associated with
      transporting poultry prior to slaughter have been shown to increase pathogen
      populations both in the intestinal tract and on the carcass exterior. The yeast,
      Saccharomyces boulardii, was evaluated for its ability to reduce populations of
      Salmonella and Campylobacter in broiler chickens subjected to transport stress.
      Chicks, inoculated with individual strains of Salmonella and Campylobacter were
      held for 6 wk and then divided into two groups with half of the chickens
      receiving 10% dried yeast in the feed for 60 h. The birds were then caged and
      transported to simulate commercial conditions. After euthanatizing the birds, the
      ceca were aseptically removed and analyzed for Salmonella and Campylobacter. With
      no yeast treatment, transport stress caused the Salmonella colonization frequency
      to increase more than fivefold, from 3.3 to 16.7%. Yeast treatment significantly
      reduced the frequency of Salmonella colonization to lower than prestress levels,
      as no Salmonella were recovered from the ceca of these birds (P < 0.05). Similar
      results were obtained from birds challenged with a mixture of Salmonella and
      Campylobacter strains. Before transport, 53.3% of these chickens were positive
      for Salmonella. Transport stress increased the colonization rate to 67.5% in
      control birds, whereas the colonization of yeast-treated chickens decreased to
      40% (P < 0.05). Frequency of Campylobacter isolation from the ceca was not
      affected by treatment, but Campylobacter populations present in the ceca were
      significantly reduced in the mixed strain trial (P < 0.05).

PMID- 9276885
TI  - Preharvest sources of Salmonella colonization in turkey production.
AB  - An ecological survey was conducted from March, 1995 to February 1996 to determine
      sources of Salmonella colonization in two flocks of turkeys reared consecutively
      in a newly constructed facility. Sampling was conducted prior to placement of
      poults, at Day 0, and again at 2, 10, 14, and 18 wk. Samples were collected at
      comparable times for the second flock except that final sampling occurred at 22
      wk instead of 18 wk. Poult box liners, birds, new litter, drinkers, and air were
      sampled. Feed was collected from each shipment upon arrival at the facility.
      Feeders, drinkers, and used litter were monitored to evaluate horizontal
      transmission. Conventional methods for isolation and serological screening were
      used to analyze samples for the presence or absence of Salmonella. Prior to
      placement of the first flock, litter, drinkers, and air samples were negative for
      the presence of Salmonella, whereas drinkers were positive prior to placement of
      the second flock. Following placement of poults, 51.1, 63.8, and 22.8% of all
      litter, drinker, and air samples, respectively, were positive. Salmonella was
      isolated from 13.6% of poult box liners, 25.0% of yolk sac samples, and 53.8% of
      ceca, excluding Day 0. Salmonella was isolated from 14.8% of feed shipments and
      39.1% of feeder contents. Frequency of Salmonella detection was higher P < 0.05)
      in Flock 1 than Flock 2 for cecal and air samples. Salmonella colonization of
      turkey flocks and the spread of Salmonella within the environment was extensive
      once initial contamination of the production house occurred. Drinkers, feeders,
      litter, and air were critical sources of horizontal transmission within each pen
      as well as between pens.

PMID- 9276886
TI  - Individual and combined effects of fumonisin B1 present in Fusarium moniliforme
      culture material and T-2 toxin or deoxynivalenol in broiler chicks.
AB  - The individual and combined effects of feeding diets containing 300 mg fumonisin
      B1 (FB1), and 5 mg T-2 toxin (T-2)/kg of diet, or 15 mg/kg deoxynivalenol (DON,
      vomitoxin) from naturally contaminated wheat were evaluated in two studies in
      male broiler chicks from day of hatch to 19 or 21 d of age in Experiments 1 and
      2, respectively. When compared with controls, body weight gains were reduced 18
      to 20% by FB1, 18% by T-2, 2% by DON, 32% by the FB1 and T-2 combination, and 19%
      by the FB1 and DON combination. The efficiency of feed utilization was adversely
      affected by FB1 with or without T-2 or DON. Mortality ranged from none for the
      controls to 15% for the FB1 and T-2 combination. Relative weights of the liver
      and kidney were significantly increased by FB1 with or without T-2 or DON. Serum
      concentrations of cholesterol were increased in chicks fed FB1 with or without T
      2 or DON. Activities of aspartate aminotransferase, lactate dehydrogenase, and
      gamma glutamyltransferase were increased in chicks fed FB1 at 300 mg/kg alone and
      in combination with T-2 or DON, indicating possible tissue damage and leakage of
      the enzymes into the blood. Results indicate additive toxicity when chicks were
      fed diets containing 300 mg FB1 and 5 mg T-2/kg of diet and less than additive
      toxicity when chicks were fed 300 mg FB1 and 15 mg DON/kg of diet. Of importance
      to the poultry industry is the fact that toxic synergy was not observed for
      either of these toxin combinations and the likelihood of encountering FB1 at this
      concentration in finished feed is small. However, under field conditions with
      additional stress factors, the toxicity of these mycotoxins could be altered to
      adversely affect the health and performance of poultry.

PMID- 9276887
TI  - Application of a nonlinear regression function to evaluate the kinetics of
      antibody response to vaccines in chicken lines divergently selected for
      multitrait immune response.
AB  - To evaluate the kinetics of immune response to vaccines in chickens, antibody
      response curves were approximated to the observed antibody ratios by using a
      nonlinear regression function. New parameters, the curve maximum (ymax) and the
      time of the maximum (tmax), were calculated. The method was applied to analyze
      the kinetics of the serum antibody response to Mycoplasma gallisepticum (MG) and
      Pasteurella multocida (PM) vaccines in White Leghorn lines selected, in
      replicate, for 10 generations for high (High) and low (Low) multitrait immune
      response. Chicks were immunized at 6 wk of age with both vaccines. Serum antibody
      levels were analyzed before (0) and 1, 2, 3, 4, 5, 12, and 21 wk postvaccination
      (wpv). The High lines displayed a significantly higher response than Low to both
      MG and PM. The difference in ymax between High and Low lines was 3.25-fold for PM
      response and 1.5-fold for MG response. Low lines had a significantly (P < 0.05)
      later tmax than High lines to MG, but not to PM. There was a significant (P <
      0.05) positive correlation between the antibody responses to MG and PM, in High
      lines for the antibody ratios 0, 3, and 21 wpv and in Low lines for 0, 12, and 21
      wpv. The ymax and tmax of antibody responses to the two vaccines were not
      correlated. The results on the kinetic differences of the antibody responses to
      MG and PM suggest that the kinetics and persistence of antibody reaction have
      different genetic regulation in response to each vaccine.

PMID- 9276888
TI  - Econometric feeding and management for first cycle phase two DeKalb Delta hens.
AB  - An experiment was conducted to determine the effect of feeding method (constant
      vs variable) and method of formulation (lysine vs protein) on the performance and
      profits of first cycle, phase 2 DeKalb Delta hens from 40 to 52 wk of age as
      influenced by egg and feed prices. Treatments 1 to 5 were formulated based on
      lysine to contain 0.65 to 0.81% TSAA and fed continuously regardless of feed
      consumption (constant feeding). Treatments 6 to 10 and 11 to 15 were formulated
      based on lysine to supply 570 to 650 mg TSAA and protein to supply 580 to 660 mg
      TSAA per hen per d, respectively, and fed based on feed intake. Dietary TSAA
      level had no overall significant effect on feed consumption, egg production, egg
      weight, mortality, or body weight. Hens fed diets using the constant method of
      feeding had significantly higher egg production, egg weight, egg specific
      gravity, and body weight than hens fed diets formulated based on lysine or
      protein using the variable method of feeding. When the treatments in the two
      variable feeding methods were compared, feed consumption was significantly higher
      for hens fed diets formulated based on protein whereas egg production, egg
      weight, egg specific gravity, and body weight were not different. It was
      concluded that method of formulation (lysine vs protein) and TSAA levels required
      for maximum profits can vary from at least 570 to 821 mg per hen per d depending
      upon energy and protein cost.

PMID- 9276889
TI  - Modulation of cholesterol levels in broiler meat by dietary garlic and copper.
AB  - Male Ross x Ross 208 chickens were fed from hatching to 21 d of age either a
      control diet (based on corn and soybean meal) or the control diet supplemented
      with 0, 1.5, 3.0, and 4.5% of a commercial garlic powder in Experiments 1 and 2.
      Once the dose-response relationship was established, 3% garlic powder or 63 or
      180 mg/kg copper as cupric citrate or cupric sulfate pentahydrate were
      supplemented to the diet (Experiments 3, 4, 5, and 6). In the first two
      experiments, reductions of plasma cholesterol (P = 0.006) and triacylglycerols (P
      = 0.013) and liver (P = 0.012) and breast muscle (P = 0.165) cholesterol were
      observed in garlic-supplemented birds. Feeding either garlic powder or copper (63
      and 180 mg/kg) resulted in reduced levels of plasma cholesterol, liver
      cholesterol, blood reduced glutathione, and breast and thigh muscle cholesterol.
      Differences were significant at P < 0.05 in at least one experiment. 3-Hydroxy-3
      methylglutaryl reductase activity was decreased due to dietary garlic (P =
      0.0369), but not by pharmacological levels of dietary copper (P = 0.982). The
      activity of fatty acid synthetase was decreased in birds fed copper (P = 0.035).
      Both garlic and copper supplements decreased cholesterol 7 alpha-hydroxylase
      activity (P = 0.024 and P = 0.022, respectively). The results of these trials
      confirm the findings that garlic and copper alter lipid and cholesterol
      metabolism. However, they do not work by the same mechanism. Feeding dietary
      garlic or copper for 21 d reduced cholesterol levels of broiler meat without
      altering growth of the chickens or feed efficiency.

PMID- 9276890
TI  - Nutritional evaluation of low glucosinolate mustard meals (Brassica juncea) in
      broiler diets.
AB  - Experiments were conducted to evaluate the nutritional value of meal derived from
      low glucosinolate cultivars of mustard (Brassica juncea) in comparison to samples
      of canola meal (Brassica napus, Brassica rapa). Samples of Brassica seed (four B.
      juncea, one B. napus, and one B. rapa) were processed using laboratory procedures
      to produce oil-extracted meals, which were examined for composition (DM basis),
      and nutritional value for broiler chickens as judged by nutrient retention (AMEn,
      ileal protein digestibility) and performance. Meals derived from B. juncea
      contained more CP and less total dietary fiber (TDF) on a dry basis than either
      B. napus or B. rapa, 45.9 vs 44.6 and 43.1% CP and 27.22 vs 29.47 and 29.67% TDF,
      respectively. Acid detergent fiber (ADF) and neutral detergent fiber (NDF) levels
      for B. juncea and B. rapa meals were similar to each other, but lower than those
      of B. napus, 12.79 and 13.20 vs 20.6% ADF, and 21.15 and 19.58 vs 29.47% NDF,
      respectively. Brassica juncea meals contained more glucosinolates than B. napus
      and B. rapa, 34.3 vs 21.8 and 25.5 mumol/g total glucosinolates, respectively.
      Brassica juncea meals were equal or superior to B. napus and B. rapa meals for
      AMEn and apparent ileal protein digestibility. Similarly, broilers fed B. juncea
      meals grew as quickly and converted feed to BW gain as efficiently to 21 d of age
      as those birds fed B. napus and B. rapa meals. Feeding meal from B. rapa reduced
      growth rate and gain to feed ratio. In conclusion, the nutritional value of meal
      from low glucosinolate mustard was equal or superior to that of canola meal
      samples derived from B. napus and B. rapa cultivars.

PMID- 9276891
TI  - Effects of supplemental ascorbic acid on the energy conversion of broiler chicks
      during heat stress and feed withdrawal.
AB  - The objectives of this study were 1) to determine the effects of supplemental
      ascorbic acid (AA) on the energy conversion of broiler chicks maintained at
      thermoneutral and potential heat stress temperatures using indirect convective
      calorimetry; and 2) to determine whether changes in energy conversion are
      reflected in changes in lipid metabolism. In Experiment 1, 120 2-d-old cockerels,
      housed in two identical environmental chambers, were maintained under constant
      light (2.0 +/- 0.2 fc) and recommended thermal conditions (29.6 +/- 0.8 C; 33.4
      +/- 8.0% RH) and consumed water and feed ad libitum. Beginning on Day 8
      posthatch, one-half of the birds inside each chamber were randomly assigned and
      received feed supplemented with AA. Beginning on Day 9 posthatch, the temperature
      inside one chamber was increased to 34 C whereas the other chamber remained
      thermoneutral. This design resulted in four treatments: 1) thermoneutral (TN:
      27.7 +/- 0.8 C; 40.9 +/- 9.4% RH) and 0 mg AA/kg feed (ppm); 2) TN and 150 ppm
      AA; 3) heat stress (H: 33.8 +/- 0.5 C; 43.3 +/- 7.4% RH) and 0 ppm AA; or 4) H
      and 150 ppm AA. Also beginning on Day 9 posthatch, birds were randomly assigned
      to one of three identical, indirect convective calorimeters designed to
      accommodate TN or H. Oxygen consumption, carbon dioxide production, respiratory
      quotient, and heat production were evaluated daily for 8 h, through Day 17
      posthatch. Following calorimetric measurement, birds were returned to their
      respective caging unit/chamber for the remainder of the study. Weight gain, feed
      intake, and gain: feed were also measured over the 9-d study. Heat exposure
      depressed (P < 0.05) weight gain, feed intake, and gain:feed. Ascorbic acid
      increased (P < 0.10) weight gain. Oxygen consumption and carbon dioxide and heat
      production per kilogram0.75 decreased (P < 0.05) with age with no change in the
      respiratory quotient. Heat exposure lowered (P < 0.001) the respiratory quotient.
      A temperature by AA interaction was detected in which heat-exposed birds
      expressed lower (P < 0.10) respiratory quotients when consuming the AA
      supplemented diet. In Experiment 2, 18 2-d-old cockerels, housed in an
      environmental chamber, were maintained under constant light and recommended
      thermal conditions (29.3 +/- 0.4 C; 41.4 +/- 3.3% RH) and consumed water and feed
      ad libitum. On Day 9 posthatch, birds were deprived of feed for 24 h with ad
      libitum access to water supplemented with either 0 or 400 mg AA/L. Blood samples
      were obtained from each bird before and after feed withdrawal and
      supplementation. Supplemented birds exhibited elevated (P < 0.01) plasma AA,
      levels that were not affected by feed deprivation. Feed deprivation increased (P
      < 0.0001) plasma beta-hydroxybutyrate with no effect of AA, and decreased (P <
      0.05) plasma triglycerides in the unsupplemented birds. A feed withdrawal by AA
      interaction was detected in which plasma triglycerides remained elevated in birds
      supplemented with AA. These data suggest that supplemental AA influences body
      energy stores that are used for energy purposes during periods of reduced energy
      intake.

PMID- 9276892
TI  - Determination of metabolizable energy contents of feed ingredients for ducks.
AB  - The objective of the present experiments was to determine the AMEn and TMEn of
      various feed ingredients used in duck diets. In each of two experiments, 48
      mature, male, White Pekin ducks were assigned in pairs to 24 cages based on
      initial weight. In each experiment, 12 ducks were assigned to each of three test
      ingredients and 12 ducks received dextrose for determination of endogenous losses
      of nitrogen and energy. The test ingredients were tube-fed in wet form and
      consisted of corn, barley, and pearl millet in Experiment 1, and corn, sorghum,
      and triticale in Experiment 2. Feed was withdrawn 48 h prior to feeding the test
      ingredients and ducks were tube-fed 30 g of dextrose in 100 mL of water at 8 and
      32 h after feed withdrawal. Ducks were tube-fed 30 g of their assigned test
      ingredient in 100 mL of water at 48 and 54 h after feed withdrawal. Ducks used in
      estimating endogenous nitrogen and energy losses were tube-fed 30 g of dextrose
      in 100 mL of water at 48 and 54 h after feed withdrawal. The method of excreta
      collection utilized was surgical fixation of a collection apparatus to the vent
      area of ducks to facilitate total collection of excreta. Collection of excreta
      was initiated at the first feeding of test ingredients and was continued for a
      total of 54 h. In Experiment 1, the AMEn and TMEn of corn, barley, and pearl
      millet on an as-fed basis were determined to be 3.208 and 3.339, 2.730 and 2.863,
      and 3.350 and 3.484 kcal/g, respectively. In Experiment 2, the AMEn and TMEn of
      corn, sorghum, and triticale on an as-fed basis were determined to be 3.151 and
      3.459, 3.260 and 3.567, and 2.757 and 3.065 kcal/g, respectively. In conclusion,
      the use of the modified TME assay, in addition to total collection of excreta
      from individual ducks, provides a means of accurately estimating the ME content
      of feed ingredients used to formulate diets for ducks.

PMID- 9276894
TI  - A low-protein diet for turkey poults.
AB  - A series of studies was conducted to determine whether a low-protein corn-soybean
      meal diet would support growth of turkeys similar to that supported by a standard
      diet. Three treatments administered in a series of experiments included: basal
      diet with essential amino acids (EAA), NaHCO3, and glutamic acid added at the
      expense of sucrose to bring the total protein up to 28% (+GLU); basal diet with
      EAA, NaHCO3, and sucrose added to bring the total protein content to 22% (+SUC);
      and a 28% crude protein standard diet that meets or exceeds NRC recommendations
      using intact protein sources (ST). Essential amino acid levels used in the
      experimental diets were based on an estimated ideal protein ratio for turkeys.
      The basal diet contained 18.4% intact CP from corn and soybean meal. All
      treatments were isocaloric with 3,172 to 3,192 kcal/kg. In all trials, the birds
      receiving +GLU and +SUC had adequate growth and feed:gain responses compared to
      birds receiving ST. The low protein basal diet with appropriate amino acid
      supplementation will allow for amino acid titrations to determine digestible
      amino acid requirements.

PMID- 9276893
TI  - A new method for determining the availability of choline in soybean meal.
AB  - Studies were conducted to evaluate the availability of choline in soybean meal,
      using a new approach: The basal diet contained soybean meal with a lowered
      choline content (partially extracted with methanol). Choline was added to the
      basal diet 1) by substituting intact soybean meal for the methanol washed soybean
      meal; or 2) from crystalline choline Cl. Four experiments were conducted with day
      old male broilers housed in battery brooders and fed the experimental diets from
      4 to 18 d posthatching. The basal diet contained corn, soybean meal, and isolated
      soy protein in Experiments 1 to 3, and also glucose in Experiment 4. In
      Experiment 1, chicks fed the basal diet (1,140 mg/kg choline, 0.61% sulfur amino
      acids) had a growth response to 1,000 mg/kg choline or 0.10% methionine (P <
      0.05), but not to 0.10% cysteine (P > 0.05) supplementation. Supplementation of
      choline (0, 50, 100, 200, 400, 800, and 1,200 mg/kg) to the basal diet (1,230
      mg/kg choline) in Experiment 2 resulted in a linear increase in growth up to 122
      +/- 22 mg/kg supplemental choline (1,352 +/- 22 mg/kg total choline), reaching a
      plateau after that. In the slope ratio assays to determine choline availability,
      the basal diets in Experiments 3 (1,098 mg/kg choline) and 4 (920 mg/kg choline)
      were supplemented with either 50 or 100 mg/ kg choline (from choline Cl) or had
      approximately 50 or 100 mg/kg choline added with intact soybean meal (at the
      expense of washed soybean meal). There were significant linear responses of
      weight gain vs choline intake from either source (P < 0.001). The availability of
      choline in soybean meal was calculated to be 97 and 105% in Experiments 3 and 4,
      respectively. These results indicate that choline availability in soybean meal is
      close to 100%.

PMID- 9276895
TI  - Mesotocin receptor binding of cortical and medullary kidney tissues of the hen.
AB  - [125I]Mesotocin (MT) binding of membrane fractions of the cortical tissue and the
      medullary tissue (medullary cone) of the kidney of nonlaying hens was measured by
      the use of radioligand binding assays to determine the distribution of two
      distinct MT receptors within the hen kidney. The binding to [125I]MT in the
      medullary tissue was found to be highly competitive with unlabeled MT. In the
      cortical tissue, the binding was competitive with both unlabeled MT and arginine
      vasotocin. Kinetic and Scatchard analyses of specific binding revealed that the
      binding affinity was higher in the cortical tissue than in the medullary tissue,
      but the binding capacity was less in the cortical tissue. The localization of two
      distinct MT receptor having different binding properties may be related to the
      biphasic action of MT within the tissue of the kidney of the hen.

PMID- 9276896
TI  - Effects of environmental and social factors on incubation behavior,
      endocrinological parameters, and production traits in turkey hens (Meleagris
      gallopavo).
AB  - Hens raised in three different environments were assessed for changes in egg
      production performance, the rate of incubation behavior expression, and plasma
      levels of luteinizing hormone (LH) and prolactin for 20 wk following the laying
      of the first egg. The environments were individual (IFP) or collective floor pens
      (CFP) and individual battery cages (Cp and Cnp). The hens from three experimental
      groups (IFP, CFP, and Cp) were transferred from a short (6 h) to a long (14 h)
      photoperiod, whereas the ones from the remnant (Cnp) were left under a short one.
      Increase of the photoperiod induced significant increases (P < 0.05) in levels of
      prolactin and LH after 1 d, and resulted in the onset of egg laying in a delay of
      14 d in all groups. However, the overall egg laying performance was highest for
      the IFP hens. The CFP and IFP hens laid 98 and 24% of their eggs inside the nest
      boxes, respectively. The hens raised in battery cages did not express incubation
      behavior, whereas 50 and 33%, respectively, of the CFP and IFP hens did. During
      the 1st wk of egg laying, levels of prolactin increased for all photostimulated
      hens but to a greater extent for CFP hens. Higher increases in levels of
      prolactin were associated with the expression of incubation behavior; however,
      prolactin levels of nonincubating laying hens were also higher under the CFP
      treatment. It appears that the rate of expression of incubation behavior, as well
      as changes in the plasma levels of prolactin and LH throughout an egg production
      period, are dependent upon rearing conditions in turkey hens.

PMID- 9276897
TI  - Oviposition delays induced by social stress are reversed by treatment with the
      beta-adrenergic blocking agent propranolol.
AB  - Contact with unfamiliar conspecifics (social stress) caused hens to delay
      oviposition. These delays were prevented by propranolol (10 mg/kg), suggesting
      that beta-adrenergic receptors are involved in their physiological causation.

PMID- 9276899
TI  - Olfaction in chickens: sense and sensibility.

PMID- 9276898
TI  - Utilization of the skin attachment model to determine the antibacterial efficacy
      of potential carcass treatments.
AB  - Two experiments (EXP), utilizing the skin attachment model (SAM), were conducted
      to determine the bactericidal activity of six potential carcass disinfectants
      [EXP 1: 20, 400, and 800 ppm sodium hypochlorite; EXP 2: 5% acetic acid (AA), 8%
      trisodium phosphate (TSP), and 1% sodium metabisulfite (SS)] during simulated
      scalder (50 C for 2 min), chiller (0 C for 60 min), or post-process dip (23 C for
      15 s) application. Efficacies of treatments were determined against populations
      of Salmonella typhimurium that were "loosely" or "firmly" attached to chicken
      breast skin (10 cm diameter). For comparison, activity of the six disinfectants
      was also determined against S. typhimurium in aqueous suspension. All
      disinfectants except SS reduced numbers of freely suspended S. typhimurium by >
      or = 4.5 log10 cfu/mL. The sodium metabisulfite did not reduce populations of
      salmonellae. In both EXP, there were disinfectant by application interactions (P
      < 0.05) on activity against loosely and firmly attached cells. Sodium
      hypochlorite at 20 ppm had little activity regardless of application, whereas
      higher levels were more effective (P < 0.001), particularly in the chiller
      application, in which loosely and firmly attached populations were reduced by 2.3
      to 2.5 and 1.3 to 1.9 log10 cfu per skin, respectively. In EXP 2, SS showed no
      activity regardless of application. Trisodium phosphate was similarly effective
      (reduction by 1.2 to 1.8 log10 cfu per skin) in all applications (P > 0.05). In
      contrast, AA activity was affected by the application method (P < 0.05). Against
      loosely attached cells, AA was most effective in the chiller application (2.5
      log10 reduction), whereas against firmly attached cells, AA was effective only in
      the scalder application (2.0 log10 reduction). Attachment of S. typhimurium to
      poultry skin apparently increased the ability of the bacteria to resist various
      disinfectants, and efficacy was influenced by extent of attachment of bacteria to
      skin and method of disinfectant application.

PMID- 9276900
TI  - Proceedings of the Joint US/EU Workshop: urinary biomarkers to detect significant
      effects of environmental and occupational exposure to nephrotoxins.

PMID- 9276901
TI  - Urinary biomarkers to detect significant effects of environmental and
      occupational exposure to nephrotoxins. I. Categories of tests for detecting
      effects of nephrotoxins.

PMID- 9276902
TI  - Urinary biomarkers to detect significant effects of environmental and
      occupational exposure to nephrotoxins. II. Nephrotoxins of significant frequency
      and economic impact.

PMID- 9276903
TI  - Urinary biomarkers to detect significant effects of environmental and
      occupational exposure to nephrotoxins. III. Minimal battery of tests to assess
      subclinical nephrotoxicity for epidemiological studies based on current
      knowledge.

PMID- 9276904
TI  - Urinary biomarkers to detect significant effects of environmental and
      occupational exposure to nephrotoxins. IV. Current information on interpreting
      the health implications of tests.

PMID- 9276905
TI  - Urinary biomarkers to detect significant effects of environmental and
      occupational exposure to nephrotoxins. V. Monitoring of individuals with elevated
      test patterns.

PMID- 9276907
TI  - Urinary biomarkers to detect significant effects of environmental and
      occupational exposure to nephrotoxins. VI. Future research needs.

PMID- 9276908
TI  - Blood cell transplantation: concepts and concerns.
AB  - OBJECTIVES: To provide a review of the concepts and concerns for each phase of
      blood cell transplantation (BCT). DATA SOURCES: Review articles, research
      studies, abstracts, and book chapters related to BCT. CONCLUSIONS: The evaluation
      of BCT as a major treatment option for a growing number of diseases will
      challenge nursing professionals. BCT is a complex process that requires
      conceptual knowledge as well as technical skills. IMPLICATIONS FOR NURSING
      PRACTICE: Comprehending specific concepts related to patient eligibility,
      mobilization, apheresis, cryopreservation, dose-intensive therapy, reinfusion,
      and marrow engraftment is essential to providing quality nursing care to patients
      undergoing BCT.

PMID- 9276909
TI  - Diseases treated with blood cell transplants.
AB  - OBJECTIVES: To provide an overview of the vast amount of clinical and research
      data concerning the diseases treated with blood cell transplants. DATA SOURCES:
      Research studies, abstracts, book chapters, and articles pertaining to diseases
      treated with blood cell transplantation (BCT). CONCLUSIONS: The potential for the
      expanded use of BCT in cancer and other diseases appears unlimited. This type of
      transplantation is gaining widespread use and the number of centers offering this
      treatment for hematologic and solid tumors is increasing. IMPLICATIONS FOR
      NURSING PRACTICE: Nurses working in acute care, outpatient, and home care
      settings need to familiarize themselves with the rapidly expanding role of this
      treatment to provide the most state-of-the-art care to their patients.

PMID- 9276910
TI  - Nursing care of the blood cell transplant recipient.
AB  - OBJECTIVES: To review the complications of blood cell transplantation (BCT) and
      their clinical and nursing management. DATA SOURCES: Review articles, research
      studies, book chapters pertaining to the complications of peripheral stem cell
      transplantation and the management of these complications. CONCLUSIONS: As the
      number of patients receiving BCT increases, complications related to stem cell
      mobilization, harvesting, dose-intensive conditioning therapy, infusion, and
      engraftment are being documented with increasing accuracy. IMPLICATIONS FOR
      NURSING PRACTICE: Oncology nurses will be caring for an increasing population of
      patients undergoing BCT. Although complications of both bone marrow
      transplantation and BCT are similar there are unique differences. Support and
      nursing interventions are of utmost importance for BCT patients and their family
      caregivers.

PMID- 9276912
TI  - Blood cell transplantation: its impact on one family.
AB  - OBJECTIVES: To share a story about being the wife of a cancer survivor who had a
      blood cell transplantation (BCT). DATA SOURCES: Personal experience, and
      published articles related to the impact of cancer on the family. CONCLUSIONS:
      Cancer affects not only the patient but the entire family unit. Yet, family
      members are a forgotten population. With advances in cancer treatment,
      survivorship has increased resulting in caregiving demands that can last for
      years. The lack of research related to the impact of BCT on family members must
      be addressed. IMPLICATIONS FOR NURSING PRACTICE: There are many ways that nurses
      can provide holistic care to family members who have a loved one going through a
      BCT. Physical, psychological, social, and spiritual aspects of care can make a
      tremendous impact on the lives of patients and family members.

PMID- 9276911
TI  - Pediatric blood cell transplantation.
AB  - OBJECTIVES: To provide a review of the use of blood cell transplantation (BCT) in
      pediatric patients, the psychological and developmental issues related to BCT,
      and guidelines for supportive care. DATA SOURCES: Review articles, research
      studies, and book chapters pertaining to BCT in children with cancer.
      CONCLUSIONS: BCT is a safe and reliable source of support after myeloablative
      regimens for children with disseminated disease, relapse or failure after
      chemotherapy, or children with high-risk features at diagnosis. IMPLICATIONS FOR
      NURSING PRACTICE: The pediatric oncology nurse is an integral part of the
      multidisciplinary team in providing long-term care for children undergoing BCT.
      Astute clinical monitoring, supportive care, and management of complications is
      of utmost importance to recovery.

PMID- 9276913
TI  - Gene therapy and blood cell transplantation.
AB  - OBJECTIVES: To describe the basics of gene transfer and specific applications in
      marrow ablative therapy. DATA SOURCES: Review articles, research studies, and
      book chapters pertaining to gene therapy. CONCLUSIONS: Gene therapy will be a
      major factor in healthcare options for the 21st century. Genetically engineered
      biopharmaceuticals will probably have a place in the blood cell transplant
      regimens of the future. IMPLICATIONS FOR NURSING PRACTICE: Nurses are in a
      position to guide the successful implementation of gene therapy through their
      roles as patient educator, counselor, direct-care coordinator, consultant, and
      through development of resource materials.

PMID- 9276914
TI  - The blood cell transplant program.
AB  - OBJECTIVES: To discuss the critical components of a blood cell transplantation
      (BCT) program as they relate to the standards developed by The Foundation for
      Accreditation of Hematopoietic Cell Therapy (FAHCT). DATA SOURCES: FAHCT
      Standards, book chapters, and articles pertaining to developing a BCT program.
      CONCLUSIONS: BCT is a burgeoning therapy for oncologic and hematologic diseases.
      New regulations have emerged to promote quality medical and laboratory practice
      in blood and marrow transplantation. IMPLICATIONS FOR NURSING PRACTICE: As BCT
      increases for oncologic and hematologic diseases, a growing number of oncology
      nurses will be caring for BCT recipients and their families. Nurses in
      administration, research, advance practice, and education are increasingly
      involved in implementing BCT as a standard therapy for a growing number of
      diseases.

PMID- 9276915
TI  - Future considerations in transplantation.

PMID- 9276916
TI  - Acid-base behavior of quinolones in aqueous acetonitrile mixtures.
AB  - Quinolones are a family of antibacterial agents that are used extensively in both
      human and veterinary clinics. Their antibacterial activity is pH-dependent, and
      therefore an examination of protonation equilibria in quinolone solutions is
      essential. pK-Values of nine quinolone antibacterials in acetonitrile-water
      mixtures containing 0, 10, 30, 40, 50 and 70%(w/w) acetonitrile were determined
      according to the rules and procedures endorsed by IUPAC. In order to obtain
      quinolone pK-values in any acetonitrile-water mixture up to 70%(w/w)
      acetonitrile, relationships between pK-values and different bulk properties (such
      as dielectric constant) and some microscopic parameters (such as solvatochromic
      parameters alpha, beta and pi*) were established. These relationships and the
      application of the preferential solvation theory of electrolytes in acetonitrile
      water mixtures permit the interpretation of acid-base behaviour of these
      important antimicrobials in the widely used acetonitrile-water media.

PMID- 9276917
TI  - Structural determination of a dimeric side-product accompanying dihydropyrazine
      preparation.
AB  - The identity of a major side-product of attempted 2,3-dihydropyrazine
      dehydrogenation has been elucidated using a geminal dimethyl analog [2,2,5,6
      tetramethyl-2,3-dihydropyrazine (1)] which cannot aromatize. 1H, 13C NMR and GC
      MS analyses were consistent with the formulation of the product as a symmetrical
      dimer of 1, but did not allow unambiguous distinction between two possible
      isomers, each of which could exist as either syn or anti diastereoisomers. X-Ray
      diffraction studies identified the product as the anti isomer of 3,3,5a,8,8,10a
      hexamethyl-1,2,3,5,5a,6,7,8,10,10a-decahydropyra zino [2,3-g] quinoxaline (2).
      Compound 2 crystallizes in the tetragonal space group I41/a (No. 88) with a =
      12.090(1), c = 22.007 (3) A, V = 3216.8(7) A3 and Z = 8. The solid-state
      structure also displays extensive hydrogen bonding between molecules of 2. A
      likely mechanism for the formation of 2 is presented.

PMID- 9276919
TI  - 5,8-Dimethoxy-1-naphthoic acid and methyl 5,8-dimethoxy-1-naphthoate.
AB  - In 5,8-dimethoxy-1-naphthoic acid, C13H12O4, hydrogen bonding is of the cyclic
      dimer type. The acid H atom is modelled as being distributed equally over two
      sites. In addition to the conventional hydrogen bonds, there are three
      significantly attractive C-H...O interactions. The dihedral angle between the
      naphthalene core plane and the carboxyl plane is 80.0 (1) degrees. In methyl 5,8
      dimethoxy-1-naphthoate, C14H14O4, there are no conventional hydrogen bonds but
      there are three significantly attractive C-H...O interactions. With the exception
      of the C-O distances in the carboxyl groups, the molecular geometries of the acid
      and the ester are quite similar.

PMID- 9276918
TI  - trans-diaquabis(2,2'-bipyridine-N,N')-ruthenium(II) bis(hexafluorophosphate).
AB  - The Ru atom of the title complex, [Ru(C10H8N2)2-(H2O)2](PF6)2, is located on a
      crystallographic inversion center; the bipyridine ligands are bowed [dihedral
      angle between C5N planes is 162.68 (12) degrees] due to the interligand steric
      interactions of the trans bipyridyl units. The Ru--O distance is 2.116 (2) A and
      the mean Ru--N distance is 2.074 (2) A.

PMID- 9276920
TI  - Anthracene-1-carboxylic acid.
AB  - The title compound, C15H10O2, was found to crystallize in the centrosymmetric
      space group P2(1)/n. The hydrogen bonding is of the cyclic dimer type about a
      center of symmetry. The carboxyl O atoms are ordered as is the carboxyl H atom.
      The anthracene core, while less nearly planar, shows good agreement with the
      anthracene cores of anthracene-9-carboxylic acid and anthracene-1,6-dicarboxylic
      acid. The carboxyl group plane makes a dihedral angle of 12.4 (2) degrees with
      the best-fit anthracene core plane.

PMID- 9276921
TI  - A diiodo-substituted 9-anthracenone.
AB  - The central ring of the anthrone system in 1,8-diiodo-10-hydroxy-10-(3-methylbut
      3-en-1-ynyl)anthrac en-9(10H)-one, C19H12I2O2, has a boat conformation and the
      two outer rings form a dihedral angle of 41.1 (2) degrees. The I-C bond lengths
      are 2.094 (4) and 2.083 (4) A. The hydroxyl and carbonyl groups form an
      intermolecular hydrogen bond having an O...O distance of 2.853 (4) A.

PMID- 9276922
TI  - Molecular chaperones, folding catalysts, and the recovery of active recombinant
      proteins from E. coli. To fold or to refold.
AB  - The high-level expression of recombinant gene products in the gram-negative
      bacterium Escherichia coli often results in the misfolding of the protein of
      interest and its subsequent degradation by cellular proteases or its deposition
      into biologically inactive aggregates known as inclusion bodies. It has recently
      become clear that in vivo protein folding is an energy-dependent process mediated
      by two classes of folding modulators. Molecular chaperones, such as the DnaK-DnaJ
      GrpE and GroEL-GroES systems, suppress off-pathway aggregation reactions and
      facilitate proper folding through ATP-coordinated cycles of binding and release
      of folding intermediates. On the other hand, folding catalysts (foldases)
      accelerate rate-limiting steps along the protein folding pathway such as the
      cis/trans isomerization of peptidyl-prolyl bonds and the formation and
      reshuffling of disulfide bridges. Manipulating the cytoplasmic folding
      environment by increasing the intracellular concentration of all or specific
      folding modulators, or by inactivating genes encoding these proteins, holds great
      promise in facilitating the production and purification of heterologous proteins.
      Purified folding modulators and artificial systems that mimic their mode of
      action have also proven useful in improving the in vitro refolding yields of
      chemically denatured polypeptides. This review examines the usefulness and
      limitations of molecular chaperones and folding catalysts in both in vivo and in
      vitro folding processes.

PMID- 9276923
TI  - Analysis of biomass cellulose in simultaneous saccharification and fermentation
      processes.
AB  - A direct method for determining the cellulose content of biomass residues
      resulting from simultaneous saccharifiaction and fermentation (SSF) experiment
      has been developed and evaluated. The method improves on classical cellulose
      assays by incorporating the enzymatic removal of yeast glucans from the biomass
      residue prior to acid hydrolysis and subsequent quantification of cellulose
      derived glucose. An appropriate cellulase-free, commercially available, yeast
      lysing enzyme preparation from Cytophaga was identified. A freeze-drying step was
      identified as necessary to render the SSF yeast cells susceptible to enzymatic
      lysis. The method was applied to the analysis of cellulose and yeast-associated
      glucans in SSF residues from three pretreated feedstocks; hybrid poplar,
      switchgrass, and cornstover. Cellulose assays employing the lysing-enzyme
      preparation demonstrated relative errors up to 7.2% when yeast-associated glucans
      were not removed prior to analysis of SSF residues. Enzymatic lysis of SSF yeast
      cells may be viewed as a general preparatory procedure to be used prior to
      subsequent chemical and physical analysis of SSF residues.

PMID- 9276924
TI  - Photosensitization of the yeast Phaffia rhodozyma at a low temperature for
      screening carotenoid hyperproducing mutants.
AB  - Phaffia rhodozyma strain Ant-1 produces more carotenoids, known as antioxidants,
      but it was more sensitive to light plus toluidine blue O (TBO), a superoxide
      producer, than wild strain 67-385 at 20 degrees C. Carotenoid hyperproducing
      mutants (CHMs), Ant-1 and 2A2N, exhibited decreased activity of superoxide
      dismutase (SOD) compared to 67-385, and this is in part responsible for
      hypersensitivity of the mutants to photosensitization. Light plus TBO at 2
      degrees C allowed carotenoid hyperproducing mutants to produce higher colony
      forming units than the wild-type. Photosensitization with limited cell metabolism
      by a low temperature, provides an idea of selective conditions for carotenoid
      hyperproducers of P. rhodozyma.

PMID- 9276925
TI  - Improved heterologous expression of the white-rot fungal ligninase H8 by
      crossover linker mutagenesis.
AB  - Using the crossover-linker mutagenesis method, the 5' noncoding region of the
      lambda ML-1 cDNA, which encodes the ligninase H8 isozyme of the white-rot fungus,
      Phanerochaete chrysosporium, was deleted with the simultaneous insertion of the
      putative Spodoptera frugiperda ribosome-binding sequence (RBS) (TATAAAT) directly
      in front of the translation-initiation codon of this gene. A recombinant
      baculovirus, pVL-Mu-H8, carrying the ligninase-H8 gene was successfully
      constructed, as determined by both sequence analysis and dot blot hybridization.
      A more than 18-fold increase in the expression of ligninase H8, compared to the
      previous pEV11-1A.3 recombinant baculovirus, was detected in the Sf-21 insect
      cells. This enzyme was detected within 3 d postinfection and was biologically
      active, capable of oxidizing the model lignin compound, veratryl alcohol. The
      molecular weight of the overexpressed 42 kD protein was similar to that of the
      native fungal ligninase-H8 isozyme and it also reacted specifically with the anti
      H8 monoclonal antibody (MAb 2D4.9) in Western blot analysis.

PMID- 9276926
TI  - Improvement of lysine production by analog-sensitive and auxotroph mutants of the
      acetylene-utilizing bacterium Gordona bronchialis (Rhodococcus bronchialis).
AB  - An acetylene utilizing Gordona (Rhodococcus) bronchialis strain, screened for the
      production of fine chemicals, was found to be capable of producing small amounts
      of lysine. Attempts to produce amino-acid analog-resistant and/or sensitive
      mutants and auxotrophs of this strain with increased lysine production were made
      following UV-irradiation or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)
      treatment. The bacterium exhibited surprisingly high resistance levels to the
      aforementioned mutagens which is attributed to highly effective inborn-repair
      systems. Natural resistance to high levels of S-(2-aminoethyl)-L-cysteine (AEC)
      (2%) was observed, in contrast with D, L-aspartic acid hydroxamate (AAH), L
      lysine hydroxamate (LHX) and beta-fluoropyruvate (FP). A variety of amino-acid
      analog-resistant (AAHr, LHXr) or analog-sensitive (FPs) mutants were produced
      following UV-irradiation or MNNG treatment. Similarly, a large number of
      auxotrophs (68) of different types were also obtained. From these, one FPs mono
      auxotroph and two poly-auxotrophs (with at least one requirement for the aspartic
      acid family) showed an increased lysine production (approximately 1.8 g/L)
      comparable (4 g/L) to that found in other bacteria capable of utilizing long
      chain hydrocarbons (1).

PMID- 9276927
TI  - Biochemistry of S-layers.
AB  - During evolution prokaryotes have developed different envelope structures
      exterior to the cell wall proper. Among these surface components are regularly
      arranged S-layers and capsules. The structural characterization and the detailed
      chemical analysis of these surface molecules is a prerequisite to understand
      their biosynthesis and functional role(s) at the molecular level. Of particular
      interest are the glycosylated S-layer proteins which belong to the first
      prokaryotic glycoproteins ever described. Their characterization was performed on
      strains belonging to the thermophilic Bacillaceae and included structural studies
      and experiments to learn about the pathways for the glycan biosynthesis of S
      layer glycoproteins. As an example for non-glycosylated S-layer proteins those of
      Lactobacillus helveticus strains are described in detail. Recently, a novel type
      of bacterial glycoconjugate was observed in the cell envelope of the extremely
      halophilic archaeon Natronococcus occultus which consists of a glycosylated
      polyglutamyl polymer. Beside the conventional biochemical techniques for the
      analysis new sophisticated instrumental methods such as X-ray photoelectron
      spectroscopy and matrix-assisted laser desorption ionization or electrospray
      ionization mass spectrometry have been introduced for the analysis of the protein
      and glycan portions of these cell surface macromolecules.

PMID- 9276928
TI  - Molecular biology of S-layers.
AB  - In this chapter we report on the molecular biology of crystalline surface layers
      of different bacterial groups. The limited information indicates that there are
      many variations on a common theme. Sequence variety, antigenic diversity, gene
      expression, rearrangements, influence of environmental factors and applied
      aspects are addressed. There is considerable variety in the S-layer composition,
      which was elucidated by sequence analysis of the corresponding genes. In
      Corynebacterium glutamicum one major cell wall protein is responsible for the
      formation of a highly ordered, hexagonal array. In contrast, two abundant surface
      proteins from the S-layer of Bacillus anthracis. Each protein possesses three S
      layer homology motifs and one protein could be a virulence factor. The antigenic
      diversity and ABC transporters are important features, which have been studied in
      methanogenic archaea. The expression of the S-layer components is controlled by
      three genes in the case of Thermus thermophilus. One has repressor activity on
      the S-layer gene promoter, the second codes for the S-layer protein. The
      rearrangement by reciprocal recombination was investigated in Campylobacter
      fetus. 7-8 S-layer proteins with a high degree of homology at the 5' and 3' ends
      were found. Environmental changes influence the surface properties of Bacillus
      stearothermophilus. Depending on oxygen supply, this species produces different S
      layer proteins. Finally, the molecular bases for some applications are discussed.
      Recombinant S-layer fusion proteins have been designed for biotechnology.

PMID- 9276929
TI  - Functions of S-layers.
AB  - Although S-layers are being increasingly identified on Bacteria and Archaea, it
      is enigmatic that in most cases S-layer function continues to elude us. In a few
      instances, S-layers have been shown to be virulence factors on pathogens (e.g.
      Campylobacter fetus ssp. fetus and Aeromonas salmonicida), protective against
      Bdellovibrio, a depository for surface-exposed enzymes (e.g. Bacillus
      stearothermophilus), shape-determining agents (e.g. Thermoproteus tenax) and
      nucleation factors for fine-grain mineral development (e.g. Synechococcus GL 24).
      Yet, for the vast majority of S-layered bacteria, the natural function of these
      crystalline arrays continues to be evasive. The following review up-dates the
      functional basis of S-layers and describes such diverse topics as the effect of S
      layers on the Gram stain, bacteriophage adsorption in lactobacilli, phagocytosis
      by human polymorphonuclear leukocytes, the adhesion of a high-molecular-mass
      amylase, outer membrane porosity, and the secretion of extracellular enzymes of
      Thermoanaerobacterium. In addition, the functional aspect of calcium on the
      Caulobacter S-layer is explained.

PMID- 9276930
TI  - Applications of S-layers.
AB  - The wealth of information existing on the general principle of S-layers has
      revealed a broad application potential. The most relevant features exploited in
      applied S-layer research are: (i) pores passing through S-layers show identical
      size and morphology and are in the range of ultrafiltration membranes; (ii)
      functional groups on the surface and in the pores are aligned in well-defined
      positions and orientations and accessible for binding functional molecules in
      very precise fashion; (iii) isolated S-layer subunits from many organisms are
      capable of recrystallizing as closed monolayers onto solid supports at the air
      water interface, on lipid monolayers or onto the surface of liposomes.
      Particularly their repetitive physicochemical properties down to the subnanometer
      scale make S-layers unique structures for functionalization of surfaces and
      interfaces down to the ultimate resolution limit. The following review focuses on
      selected applications in biotechnology, diagnostics, vaccine development,
      biomimetic membranes, supramolecular engineering and nanotechnology. Despite
      progress in the characterization of S-layers and the exploitation of S-layers for
      the applications described in this chapter, it is clear that the field lags
      behind others (e.g. enzyme engineering) in applying recent advances in protein
      engineering. Genetic modification and targeted chemical modification would allow
      several possibilities including the manipulation of pore permeation properties,
      the introduction of switches to open and close the pores, and the covalent
      attachment to surfaces or other macromolecules through defined sites on the S
      layer protein. The application of protein engineering to S-layers will require
      the development of straightforward expression systems, the development of simple
      assays for assembly and function that are suitable for the rapid screening of
      numerous mutants and the acquisition of structural information at atomic
      resolution. Attention should be given to these areas in the coming years.

PMID- 9276931
TI  - Identification and characterization of microsatellites in Norway spruce (Picea
      abies K.).
AB  - Norway spruce (Picea abies) genomic libraries were screened for presence of
      dinucleotide AC/GT and AG/CT microsatellites (or simple sequence repeats). On
      average, one (AG)n microsatellite every 194 kb and one (AC)n microsatellite every
      406 kb were found. Forty-six positive clones were sequenced and primers flanking
      24 AG microsatellites and 12 AC microsatellites diesigned. Only seven (20%) of
      them produced the expected single-locus polymorphic pattern when used to amplify
      Norway spruce DNAs. The other primer pairs gave either multiple bands or bad
      amplification, or a single monomorphic fragment. Such a small proportion of
      successful primer pairs was attributed to the high level of complexity of the
      Norway spruce genome. Dot blot analysis of the clones showed that many of them
      contained repetitive DNA and that those giving the single-locus polymorphic
      patterns usually corresponded to single-copy sequences. A family of repetitive
      DNA that contained AG repeats was identified and was present in about 40,000
      copies per haploid genome. Simple Mendelian inheritance was observed for all the
      polymorphisms tested. The average number of alleles was 13, ranging from 6 to 22,
      and the expected heterozygosity was 0.79 when seven microsatellites were used to
      genotype a panel of 18 trees representing different populations. Compared with
      isozymes, microsatellites are about five times more informative and could provide
      an extremely valuable source of markers for genome mapping and genetic diversity
      studies.

PMID- 9276932
TI  - Simple sequence repeats in watermelon (Citrullus lanatus (Thunb.) Matsum. &
      Nakai).
AB  - Simple sequence repeat length polymorphisms were utilized to examine genetic
      relatedness among accessions of watermelon (Citrullus lanatus (Thunb.) Matsum. &
      Nakai). A size-fractionated TaqI genomic library was screened for the occurrence
      of dimer and trimer simple sequence repeats (SSRs). A total of 96 (0.53%) SSR
      bearing clones were identified and the inserts from 50 of these were sequenced.
      The dinucleotide repeats (CT)n and (GA)n accounted for 82% of the SSRs sequenced.
      PCR primer pairs flanking seven SSR loci were used to amplify SSRs from 32
      morphologically variable watermelon genotypes from Africa, Europe, Asia, and
      Mexico and a single accession of Citrullus colocynthis from Chad. Cluster
      analysis of SSR length polymorphisms delineated 4 groups at the 25% level of
      genetic similarity. The largest group contained C. lanatus var. lanatus
      accessions. The second largest group contained only wild and cultivated "citron"
      type or C. lanatus var. citroides accessions. The third group contained an
      accession tentatively identified as C. lanatus var. lanatus but which perhaps is
      a hybrid between C. lanatus var. lanatus and C. lanatus var. citroides. The
      fourth group consisted of a single accession identified as C. colocynthis.
      "Egusi"-type watermelons from Nigeria grouped with C. lanatus var. lanatus. The
      use of SSRs for watermelon germplasm characterization and genetic diversity
      studies is discussed.

PMID- 9276933
TI  - Discriminating between barley genotypes using microsatellite markers.
AB  - Eleven microsatellite loci were used to survey 24 barley genotypes representing
      23 cultivars and a breeding line in official trials. Three separate combinations
      of four microsatellites had overall probabilities of identity of less than 1 in
      1000 and could distinguish between all 24 barley genotypes. It is shown that the
      microsatellites could distinguish genotypes with the same pedigree and also that
      patterns of discrimination were different from those obtained from botanical
      descriptors. The stability of microsatellites across different generations was
      demonstrated by a retrospective analysis of the pedigree of Golden Promise. One
      of the parents of Maythorpe, the immediate ancestor of Golden Promise, was shown
      to be Irish Goldthorpe rather than Goldthorpe, thereby resolving conflicting
      published pedigrees.

PMID- 9276934
TI  - Three novel T-box genes in Caenorhabditis elegans.
AB  - The T-box gene family consists of members that share a unique DNA binding domain.
      The best characterized T-box gene, Brachyury or T, encodes a transcription factor
      that plays an important role in early vertebrate development. Seven other
      recently described mouse T-box genes are also expressed during development. In
      the nematode Caenorhabditis elegans, four T-box genes have been characterized to
      date. In this study, we describe three new C. elegans T-box genes, named Ce-tbx
      11, Ce-tbx-12, and Ce-tbx-17. Ce-tbx-11 and Ce-tbx-17 were uncovered through the
      sequencing efforts of the C. elegans Genome Project. Ce-tbx-12 was uncovered
      through degenerate PCR analysis of C. elegans genomic DNA. Ce-tbx-11 and Ce-tbx
      17 are located in close proximity to the four other previously described T-box
      genes in the central region of chromosome III. In contrast, Ce-tbx-12 maps alone
      to chromosome II. Phylogenetic analysis of all known T-box domain sequences
      provides evidence of an ancient origin for this gene family.

PMID- 9276935
TI  - A complex arrangement of genes at a starch branching enzyme I locus in the D
      genome donor of wheat.
AB  - Genomic DNA fragments from Triticum tauschii (D-genome donor to wheat) carrying
      starch branching enzyme I (SBE I) type genes have been characterized. One
      fragment contains one complete gene and two partial genes in 16 kb of DNA. One of
      the partial genes is oriented in the opposite strand to the other two. The gene
      that is complete was sequenced. Its structure corresponds closely to that of rice
      in that exons 3-8 are retained at similar sizes and spacings. A cDNA closely
      corresponding to the complete gene was isolated and characterized; it codes for a
      putative protein that represents a novel type of SBE I, as it is shorter at the
      3' end than the forms reported so far in other plants. A second genomic fragment
      contains a different SBE I gene. There appear to be approximately 10 copies of
      SBE I type genes in wheat (approximately 5 in T. tauschii) and most of them have
      been assigned to group 7 chromosomes. In situ hybridization indicates that a
      major locus for the genes is located at the distal end of the short arm of
      chromosome 7D.

PMID- 9276936
TI  - Genetic diversity among a complex of cereal cyst nematodes inferred from RFLP
      analysis of the ribosomal internal transcribed spacer region.
AB  - This study examined the restriction polymorphism (RFLP) of the nuclear ribosomal
      DNA in Heterodera avenae, H. filipjevi, H. mani, H. latipons, and the
      taxonomically unclear Gotland strain in order to establish a molecular
      characterization and phylogenetic relationships in the complex of cereal cyst
      nematodes (CCN). The internal transcribed spacer (ITS) and 5.8S rDNA were
      amplified by PCR from a single female or a cyst of 27 different geographic
      isolates of the CCN complex and one population of H. schachtii, used as outgroup.
      The amplified product was 1.2 kb long and 14 of 15 enzymes produced restriction
      fragments for each isolate. Relationships between populations were determined
      from UPGMA analysis based on distance values calculated from RFLP data.
      Digestions with TaqI clearly differentiated H. avenae, H. latipons, and a group
      composed of H. filipjevi and the Gotland strain. Six endonucleases (HaeIII,
      HinfI, ItaI, PstI, TaqI, and Tru9I) produced the same restriction pattern with H.
      filipjevi and the Gotland strain, and both were clearly separated from H. avenae
      with PstI. Restriction sites have revealed a mixture of the species H. latipons
      and H. avenae, and possible infraspecific variation in H. avenae. The inferred
      phylogenetic relationships of species in the CCN complex are in agreement with
      their morphological characterization.

PMID- 9276937
TI  - Genome analysis of South American Elymus (Triticeae) and Leymus (Triticeae)
      species based on variation in repeated nucleotide sequences.
AB  - Variation in repeated nucleotide sequences (RNSs) at the level of entire families
      assayed by Southern blot hybridization is remarkably low within species and is a
      powerful tool for scrutinizing the origin of allopolyploid taxa. Thirty-one
      clones from RNSs isolated from different Triticeae genera were used to
      investigate the genome constitution of South American Elymus. One of these
      clones, pHch2, preferentially hybridized with the diploid H genome Hordeum
      species. Hybridization of this clone with a worldwide collection of Elymus
      species with known genome formulas showed that pHch2 clearly discriminates Elymus
      species with the H genome (StH, StHH, StStH, and StHY) from those with other
      genome combinations (StY, StStY, StPY, and StP). Hybridization with pHch2
      indicates the presence of the H genome in all South American Elymus species
      except Elymus erianthus and Elymus mendocinus. Hybridization with additional
      clones that revealed differential restriction fragments (marker bands) for the H
      genome confirmed the absence of the H genome in these species. Differential
      restriction fragments for the Ns genome of Psathyrostachys were detected in E.
      erianthus and E. mendocinus and three species of Leymus. Based on genome
      constitution, morphology, and habitat, E. erianthus and E. mendocinus were
      transferred to the genus Leymus.

PMID- 9276938
TI  - A novel RNA species from the turtle mitochondrial genome: induction and
      regulation of transcription and processing under anoxic and freezing stresses.
AB  - The present study identifies a previously cloned cDNA, pBTaR914, as homologous to
      the mitochondrial WANCY (tryptophan, alanine, asparagine, cysteine, and tyrosine)
      tRNA gene cluster. This cDNA clone has a 304-bp sequence and its homologue,
      pBTaR09, has a 158-bp sequence with a long poly(A)+ tail (more than 60
      adenosines). RNA blotting analysis using pBTaR914 probe against the total RNA
      from the tissues of adult and hatchling turtles revealed five bands: 540, 1800,
      2200, 3200, and 3900 nucleotides (nt). The 540-nt transcript is considered to be
      an intact mtRNA unit from a novel mtDNA gene designated WANCYHP that overlaps the
      WANCY tRNA gene cluster region. This transcript was highly induced by both anoxic
      and freezing stresses in turtle heart. The other transcripts are considered to be
      the processed intermediates of mtRNA transcripts with WANCYHP sequence. All these
      transcripts were differentially regulated by anoxia and freezing in different
      organs. The data suggest that mtRNA processing is sensitive to regulation by
      external stresses, oxygen deprivation, and freezing. Furthermore, the fact that
      the WANCYHP transcript is highly induced during anoxic exposure suggests that it
      may play an important role in the regulation of mitochondrial activities to
      coordinate the physiological adaptation to anoxia.

PMID- 9276939
TI  - Barley elongation factor 1 alpha: genomic organization, DNA sequence, and
      phylogenetic implications.
AB  - A full length cDNA clone encoding the 447 amino acid long barley (Hordeum vulgare
      cv. Bomi) endosperm elongation factor 1 alpha (eF-1 alpha) was isolated by a
      differential screening procedure. RFLP mapping of eF-1 alpha showed that the
      barley genome contains a small eF-1 alpha gene family of 4 copies, with 1 copy of
      the gene being located on each of chromosomes 2, 4, 6, and 7. Analysis of barley
      endosperm total proteins by Western blot with antibodies directed towards wheat
      eF-1 alpha and the sea urchin 51 kDa proteins gave a single band of the expected
      molecular weight. Amino acid sequence comparison with other plant eF-1 alpha
      sequences showed that the isolated barley endosperm eF-1 alpha is more similar to
      the published wheat eF-1 alpha sequence than to eF-1 alpha sequences previously
      published for the barley cultivars Igri and Dicktoo. The phylogenetic analysis
      suggests that the barley eF-1 alpha gene family can be divided into two
      subfamilies and that two ancestral genes existed before the divergence of
      monocotyledonous and dicotyledonous plants.

PMID- 9276940
TI  - Phospholipase activity in Cryptococcus neoformans.
AB  - Phospholipases have only been detected in a few fungi and yeasts, in particular
      in Candida albicans. Secreted phospholipases are considered by some researchers
      to be a potential factor of virulence and pathogenicity in C. albicans. Twenty
      three Cryptococcus neoformans strains were tested in order to observe
      phospholipase production. Twenty-two of the 23 strains tested were able to
      produce phospholipases, and the ratio diameter of the colony to total diameter of
      the colony plus zone of precipitation (Pz) ranged between 0.271 and 0.949. C.
      neoformans, just like C. albicans, can be divided on the basis of the Pz into
      different strains according to their virulence and pathogenicity. There also
      appeared to be a correlation between the phospholipase production and the size of
      the capsule in the strains isolated from AIDS patients. For this reason, further
      studies on C. neoformans phospholipase activity would be useful in evaluating the
      virulence of different strains.

PMID- 9276942
TI  - Heat generation and dissipation in plants: can the alternative oxidative
      phosphorylation pathway serve a thermoregulatory role in plant tissues other than
      specialized organs?
AB  - A number of hypothetical physiological roles have been proposed for the cyanide
      insensitive alternative pathway in plants (Palmer, 1976; Laties, 1982; Meeuse,
      1984; Purvis and Shewfelt, 1994; Wagner and Krab, 1995). The calorimetric
      observations of Raskin and co-workers (Ordentlich et al., 1991; Nevo et al.,
      1992; Moynihan et al., 1995) are significant contributions showing an interesting
      metabolic, chilling-induced response of the alternative pathway activity and
      differences in the low-temperature response among species adapted to different
      climates. Since different oxidative pathways do not have large differences in
      enthalpy, and observed heat rate increases are insufficient to cause significant
      temperature increases of physiological importance in nonthermogenic plants, other
      explanations must be developed for the relationship between the partitioning of
      electron flow and physiological conditions such as low temperature. The induction
      and engagement of the alternative respiratory pathway is involved in metabolic
      stasis, maintaining proper balance between carbon flow, ATP-ADP ratio, and
      electron flow during fluctuating or extreme temperature conditions. The
      alternative oxidase is engaged when ATP requirements are adequately met, as
      discussed by Palmer (1976), Meeuse (1983), Lambers (1985), and Wagner and Krab
      (1995). The expression and kinetic activity of the alternative oxidase are
      regulated by concentrations of key metabolites (Day and Wiskich, 1995; Siedow and
      Umbach, 1995; Wagner and Krab, 1995; Day et al., 1996). Dynamic partitioning of
      electron flow between Cyt oxidase and the alternative oxidase depends on the
      kinetic behavior of the two oxidases and the substrate dehydrogenases (Day and
      Wiskich, 1995; Siedow and Umbach, 1995; Wagner and Krab, 1995; Day et al., 1996).
      Furthermore, Moynihan et al. (1995) found that Episces cupreata Hook, adapted to
      the tropics, has very little alternative oxidase activity compared with wheat
      (Nevo et al., 1992), adapted to a large range of temperature climates. This
      results is consistent with the general relation between the apparent alternative
      oxidase activity and the climate of origin of the species.

PMID- 9276941
TI  - Effect of amphotericin B on the lipids of yeast cells of Sporothrix schenckii.
AB  - Yeast cells of five strains of Sporothrix schenckii were obtained for partial
      analysis of lipid composition. Quantitative analysis of lipids and sterols were
      completed, as well as qualitative analysis of sterols by thin layer
      chromatography and by ultraviolet spectra. These determinations were made on
      cells cultured in the absence and presence of amphotericin B at sub-MIC (minimum
      inhibitory concentration) levels. Marked alterations in lipid content were
      observed in the amphotericin B-treated cells. The major alterations were the
      reduction of total lipid (18.7-57.6%) and sterols (48.5-96.7%) after exposure to
      the polyenic antibiotic. It is concluded that amphotericin B altered the lipid
      profiles, especially sterols of S. schenckii.

PMID- 9276943
TI  - Roles of higher plant K+ channels.

PMID- 9276944
TI  - Patch-clamping and other molecular approaches for the study of plasma membrane
      transporters demystified.

PMID- 9276945
TI  - High-yield expression of pea thioredoxin m and assessment of its efficiency in
      chloroplast fructose-1,6-bisphosphatase activation.
AB  - A cDNA clone encoding pea (Pisum sativum L.) chloroplast thioredoxin (Trx) m and
      its transit peptide were isolated from a pea cDNA library. Its deduced amino acid
      sequence showed 70% homology with spinach (Spinacia oleracea L.) Trx m and 25%
      homology with Trx f from pea and spinach. After subcloning in the Ndel-BamHI
      sites of pET-12a, the recombinant supplied 20 mg Trx m/L. Escherichia coli
      culture. This protein had 108 amino acids and was 12,000 D, which is identical to
      the pea leaf native protein. Unlike pea Trx f, pea Trx m showed a hyperbolic
      saturation of pea chloroplast fructose-1,6-bisphosphatase (FBPase), with a Trx m/
      FBPase molar saturation ratio of about 60, compared with 4 for the Trx f/FBPase
      quotient. Cross-experiments have shown the ability of pea Trx m to activate the
      spinach chloroplast FBPase, results that are in contrast with those in spinach
      found by P. Schurmann, K. Maeda, and A. Tsugita ([1981] Eur J Biochem 116: 37
      45), who did not find Trx m efficiency in FBPase activation. This higher
      efficiency of pea Trx m could be related to the presence of four basic residues
      (arginine-37, lysine-70, arginine-74, and lysine-97) flanking the regulatory
      cluster; spinach Trx m lacks the positive charge corresponding to lysine-70 of
      pea Trx m. This has been confirmed by K70E mutagenesis of pea Trx m, which leads
      to a 50% decrease in FBPase activation.

PMID- 9276946
TI  - Developmental regulation of pyrroline-5-carboxylate reductase gene expression in
      Arabidopsis.
AB  - At-P5R, a gene encoding the last enzyme of the proline (Pro) biosynthetic pathway
      in Arabidopsis thaliana, is developmentally regulated. To characterize the cis
      elements responsible for this developmental regulation, a series of 5' deletions
      of the At-P5R promoter were transcriptionally fused to a beta-glucuronidase (GUS)
      coding region and transformed into Arabidopsis. The complete promoter of At-P5R
      directs strong GUS activity in root tips, the shoot meristem, guard cells,
      hydathodes, pollen grains, ovules, and developing seeds, all of which contain
      rapidly dividing cells and/or are undergoing changes in osmotic potential. This
      expression pattern is consistent with the function of Pro as an energy, nitrogen,
      and carbon source and as an osmoticum in response to dehydration. Promoters
      longer than 212 base pairs (bp) showed the same expression pattern, whereas those
      shorter than 143 bp did not direct any detectable GUS activity in any organs.
      This suggests that a 69-bp promoter region located between -212 and -143 bp is
      necessary to establish the tissue-specific expression of At-P5R during
      development. The Pro content measured in different organs suggests that, in
      addition to transcriptional control of the biosynthetic pathway, the transport of
      Pro may play a role in its distribution within Arabidopsis. Several aspects of
      the relationship between Pro metabolism and plant physiology are discussed.

PMID- 9276947
TI  - Purification and characterization of a novel class III peroxidase isoenzyme from
      tea leaves.
AB  - A novel, basic (isoelectric point > 10), heme peroxidase isoenzyme (TP; relative
      molecular weight = 34,660 +/- 10, mean +/- SE) that can account for a significant
      part of the ascorbate peroxidase activity in tea (Camellia sinensis) leaves has
      been purified to homogeneity. The ultraviolet/visible absorption spectrum is
      typical of heme-containing plant peroxidases, with a Soret peak at 406 nm
      (epsilon = 115 mM-1 cm-1) and an A406/A280 value of 3.4. The enzyme has a high
      specific activity for ascorbate oxidation (151 mumol min-1 mg-1), with a pH
      optimum in the range of 4.5 to 5.0. Substrate-specificity studies have revealed
      significant differences between TP and other class III peroxidases, as well as
      similarities with class I ascorbate peroxidases. TP, like ascorbate peroxidase,
      exhibits a preference for ascorbate over guaiacol, whereas other class III
      isoenzymes are characterized by 2-orders-of-magnitude higher activity for
      guaiacol than for ascorbate. TP also forms an unstable porphyrin pi cation
      radical-type compound I, which is converted to compound II within approximately 2
      min in the absence of added reductant. Amino acid sequence data show TP to be the
      first example, to our knowledge, of a class III peroxidase with a high
      specificity for ascorbate as an electron donor.

PMID- 9276948
TI  - Activation of pollen tube callose synthase by detergents. Evidence for different
      mechanisms of action.
AB  - In pollen tubes of Nicotiana alata, a membrane-bound, Ca(2+)-independent callose
      synthase (CalS) is responsible for the biosynthesis of the (1,3)-beta-glucan
      backbone of callose, the main cell wall component. Digitonin increases CalS
      activity 3- to 4-fold over a wide range of concentrations, increasing the maximum
      initial velocity without altering the Michaelis constant for UDP-glucose. The
      CalS activity that requires digitonin for assay (the latent CalS activity) is not
      inhibited by the membrane-impermeant, active site-directed reagent UDP-pyridoxal
      when the reaction is conducted in the absence of digitonin. This is consistent
      with digitonin increasing CalS activity by the permeabilization of membrane
      vesicles. A second group of detergents, including 3-[(3
      cholamidopropyl)dimethylammonio]-1-propane-sulfonate (CHAPS), Zwittergent 3-16,
      and 1-alpha-lysolecithin, activate pollen tube CalS 10- to 15-fold, but only over
      a narrow range of concentrations just below their respective critical micellar
      concentrations. This activation could not be attributed to any particular
      chemical feature of these detergents. CHAPS increases maximum initial velocity
      and decreases the Michaelis constant for UDP-glucose and activates CalS even in
      the presence of permeabilizing concentrations of digitonin. Inhibition studies
      with UDP-pyridoxal indicate that activation by CHAPS occurs by recruitment of
      previously inactive CalS molecules to the pool of active enzyme. The activation
      of pollen tube CalS by these detergents therefore resembles activation of the
      enzyme by trypsin.

PMID- 9276949
TI  - Acidic phosphoprotein complex of the 60S ribosomal subunit of maize seedling
      roots. Components and changes in response to flooding.
AB  - We determined that ribosomes of seedling roots of maize (Zea mays L.) contain the
      acidic phosphoproteins (P-proteins) known to form a flexible lateral stalk
      structure of the 60S subunit of eukaryotic ribosomes. The P-protein stalk,
      composed of P0, P1, and P2, interacts with elongation factors, mRNA, and tRNA
      during translation. Acidic proteins of 13 to 15.5 kD were released as a complex
      from ribosomes with 0.4 M NH4Cl/50% ethanol. Protein and cDNA sequence analysis
      confirmed that maize ribosomes contain one type of P1, two types of P2, and a
      fourth and novel P1/P2-type protein. This novel P-protein, designated P3, has the
      conserved C terminus of P1 and P2. P1, P2, and P3 are similar in deduced mass
      (11.4-12.2 kD) and isoelectric point (4.1-4.3). A 35.5- to 36-kD acidic protein
      was released at low levels from ribosomes with 1.0 M NH4Cl/50% ethanol and
      identified as P0. Labeling of roots with [32P]inorganic phosphate confirmed the
      in vivo phosphorylation of the P-proteins. Flooding caused dynamic changes in the
      P-protein complex, which affected the potential of ribosome-associated kinases
      and casein kinase II to phosphorylate the P-proteins. We discuss possible
      alterations of the ribosomal P-protein complex and consider that these changes
      may be involved in the selective translation of mRNA in flooded roots.

PMID- 9276950
TI  - Ca(2+)-activated anion channels and membrane depolarizations induced by blue
      light and cold in Arabidopsis seedlings.
AB  - The activation of an anion channel in the plasma membrane of Arabidopsis thaliana
      hypocotyls by blue light (BL) is believed to be a signal-transducing event
      leading to growth inhibition. Here we report that the open probability of this
      particular anion channel depends on cytoplasmic Ca2+ ([Ca2+]cyt) within the
      concentration range of 1 to 10 microM, raising the possibility that BL activates
      the anion channel by increasing [Ca2+]cyt. Arabidopsis seedlings cytoplasmically
      expressing aequorin were generated to test this possibility. Aequorin
      luminescence did not increase during or after BL, providing evidence that Ca2+
      does not play a second-messenger role in the activation of anion channels.
      However, cold shock simultaneously triggered a large increase in [Ca2+]cyt and a
      110-mV transient depolarization of the plasma membrane. A blocker of the anion
      channel, 5-nitro-2-(3-phenylpropylamino)-benzoic acid, blocked 61% of the cold
      induced depolarization without affecting the increase in [Ca2+]cyt. These data
      led us to propose that cold shock opens Ca2+ channels at the plasma membrane,
      allowing an inward, depolarizing Ca2+ current. The resulting large increase in
      [Ca2+]cyt activates the anion channel, which further depolarizes the membrane.
      Although an increase in [Ca2+]cyt may activate anion channels in response to
      cold, it appears that BL does so via a Ca(2+)-independent pathway.

PMID- 9276952
TI  - The major intrinsic protein family of Arabidopsis has 23 members that form three
      distinct groups with functional aquaporins in each group.
AB  - Aquaporins, proteins that enhance the permeability of biological membranes to
      water, are widely distributed in living organisms. They are 26- to 29-kD proteins
      that belong to the major intrinsic protein (MIP) family of channels. By searching
      the Arabidopsis thaliana expressed sequence tag database and by using the
      polymerase chain reaction with oligonucleotides to conserved plant aquaporin
      domains, we identified 23 expressed Arabidopsis MIP genes. Eight of these had
      been previously identified as active aquaporins, and two additional ones are now
      reported to have water-transport activity in Xenopus laevis oocytes. One of these
      is highly expressed in suspension-cultured cells. On a dendrogram these 23 MIP
      sequences cluster into three groups: the first group has 11 members and contains
      the plasma membrane aquaporins, the second group also has 11 members and contains
      the tonoplast aquaporins, and the third group has only a single member. This MIP
      protein, provisionally called At-NLM1, is most closely related to the Gm-NOD26
      protein that is found in the bacteroid membranes of soybean (Glycine max L.)
      nodules; At-NLM1 is an active aquaporin when expressed in oocytes. With a
      semiquantitative slot-blot analysis technique, we determined the expression
      levels of 22 MIP genes in the various organs. The quantitative polymerase chain
      reaction was used to determine the effects of various stress treatments on the
      expression of NLM1.

PMID- 9276951
TI  - Construction of a Lotus japonicus late nodulin expressed sequence tag library and
      identification of novel nodule-specific genes.
AB  - A range of novel expressed sequence tags (ESTs) associated with late
      developmental events during nodule organogenesis in the legume Lotus japonicus
      were identified using mRNA differential display; 110 differentially displayed
      polymerase chain reaction products were cloned and analyzed. Of 88 unique cDNAs
      obtained, 22 shared significant homology to DNA/protein sequences in the
      respective databases. This group comprises, among others, a nodule-specific
      homolog of protein phosphatase 2C, a peptide transporter protein, and a nodule
      specific form of cytochrome P450. RNA gel-blot analysis of 16 differentially
      displayed ESTs confirmed their nodule-specific expression pattern. The kinetics
      of mRNA accumulation of the majority of the ESTs analyzed were found to resemble
      the expression pattern observed for the L. japonicus leghemoglobin gene. These
      results indicate that the newly isolated molecular markers correspond to genes
      induced during late developmental stages of L. japonicus nodule organogenesis and
      provide important, novel tools for the study of nodulation.

PMID- 9276953
TI  - The Arabidopsis 14-3-3 multigene family.
AB  - The 14-3-3 proteins are ubiquitous eukaryotic proteins and are encoded by a gene
      family in many species. We examined the 14-3-3 gene family in Arabidopsis
      thaliana and found that it contains 10 members. Four new cDNAs, GF14 epsilon,
      GF14 kappa, GF14 mu, and GF14 nu, and two new genomic clones of GF14 phi and GF14
      nu were isolated and characterized. Together with the six previously described 14
      3-3 isoforms in Arabidopsis, they constitute a complete family of 10 distinct 14
      3-3 proteins of 248 to 268 amino acids. Phylogenetic analysis revealed the
      presence of two ancient, distinct 14-3-3 gene classes in Arabidopsis and other
      plants. The epsilon forms diverged early from the other plant isoforms, and plant
      14-3-3 genes displayed a different evolutionary course from that of mammals.

PMID- 9276954
TI  - cDNA clones encoding 1,3-beta-glucanase and a fimbrin-like cytoskeletal protein
      are induced by Al toxicity in wheat roots.
AB  - A cDNA library made from mRNA of Al-treated roots of an Al-sensitive wheat
      (Triticum aestivum cv Victory) cultivar was screened with a degenerate
      oligonucleotide probe derived from the partial amino acid sequence of the Al
      induced protein TAI-18. Of seven clones that initially hybridized with the probe,
      one encoded a novel 1,3-beta-glucanase having a calculated molecular weight of
      46.3 and an isoelectric point of 6.0. Like the A6 1,3-beta-glucanase gene
      products from Brassica napus and Arabidopsis thaliana, the predicted wheat
      protein had a C-terminal extension with three potential glycosylation sites.
      Northern analysis revealed that wheat 1,3-beta-glucanase mRNA was up-regulated in
      Al-intoxicated roots, with highest expression after 12 h. The antibody to A6 1,3
      beta-glucanase from B. napus cross-reacted with a 56-kD protein that was induced
      after 24 h. A second partial cDNA clone showed similarity to genes encoding
      cytoskeletal fimbrin-like (actin-bundling) proteins. Although well studied in
      animals and fungi, fimbrins have not previously been described in plants. Fimbrin
      like transcripts were up-regulated after 24 h of Al treatment in the Al-sensitive
      wheat cv Victory. In the Al-tolerant cv Atlas 66, fimbrin-like mRNA was up
      regulated within 12 h by Al concentrations that did not inhibit root growth.
      Cellular stress associated with Al toxicity therefore causes up-regulation of a
      defense-related gene and a gene involved in the maintenance of cytoskeletal
      function.

PMID- 9276955
TI  - Partial characterization of glutathione S-transferases from wheat (Triticum spp.)
      and purification of a safener-induced glutathione S-transferase from Triticum
      tauschii.
AB  - Hexaploid wheat (Triticum aestivum L.) has very low constitutive glutathione S
      transferase (GST) activity when assayed with the chloroacetamide herbicide
      dimethenamid as a substrate, which may account for its low tolerance to
      dimethenamid in the field. Treatment of seeds with the herbicide safener
      fluxofenim increased the total GST activity extracted from T. aestivum shoots 9
      fold when assayed with dimethenamid as a substrate, but had no effect on
      glutathione levels. Total GST activity in crude protein extracts from T.
      aestivum, Triticum durum, and Triticum tauschii was separated into several
      component GST activities by anion-exchange fast-protein liquid chromatography.
      These activities (isozymes) differed with respect to their activities toward
      dimethenamid or 1-chloro-2,4-dinitrobenzene as substrates and in their levels of
      induction by safener treatment. A safener-induced GST isozyme was subsequently
      purified by anion-exchange and affinity chromatography from etiolated shoots of
      the diploid wheat species T. tauschii (a progenitor of hexaploid wheat) treated
      with the herbicide safener cloquintocet-mexyl. The isozyme bound to a
      dimethenamid-affinity column and had a subunit molecular mass of 26 kD based on
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The purified enzyme
      (designated GST TSI-1) was recognized by an antiserum raised against a mixture of
      maize (Zea mays) GSTs. Amino acid sequences obtained from protease-digested GST
      TSI-1 had significant homology with the safener-inducible maize GST V and two
      auxin-regulated tobacco (Nicotiana tabacum) GST isozymes.

PMID- 9276956
TI  - Gibberellins and stem growth in Arabidopsis thaliana. Effects of photoperiod on
      expression of the GA4 and GA5 loci.
AB  - Arabidopsis thaliana (L.) Heynh. is a quantitative long-day (LD) rosette plant in
      which stem growth is mediated by gibberellins (CAs). Application of GAs to plants
      in short-day (SD) conditions resulted in rapid stem elongation and flower
      formation, with GA4 and GA9 being equally effective, and GA1 showing lower
      activity. The effects of photoperiod on the levels of endogenous GAs were
      measured by combined gas chromatography-mass spectrometry with selected ion
      monitoring. When plants were transferred from SD to LD conditions there was a
      slight decrease in the level of GA53 and an increase in the levels of C19-GAs,
      GA9, GA20, GA1, and GA8, indicating that GA 20-oxidase activity is stimulated in
      LD conditions. Expression of GA5, which encodes GA 20-oxidase, was highest in
      elongating stems and was correlated with the rate of stem elongation. By
      contrast, GA4, which encodes 3 beta-hydroxylase, showed low expression in stems
      and its expression was not correlated with the rate of stem elongation. We
      conclude that stem elongation in LD conditions is at least in part due to
      increased expression of GA5, whereas expression of GA4 is not under photoperiodic
      control.

PMID- 9276958
TI  - Seed germination of Arabidopsis thaliana phyA/phyB double mutants is under
      phytochrome control.
AB  - We examined the photocontrol of seed germination in the phyA/phyB double mutants
      of Arabidopsis thaliana seeds. Dormant phyA/phyB seeds showed a red/far-red light
      (R/FR)-reversible induction of seed germination. This suggests the involvement of
      at least one other phytochrome, phyC, D, and/or E, in controlling seed
      germination. We designated this spectrally active phytochrome in phyA/phyB as
      phyX. The full reversibility of the R-induced germination by subsequent FR
      pulses, and the observation that the response is reversible by FR, even after a 3
      h R treatment, indicates that this phyX response belongs to the low-fluence
      response type. Thus, this phyX response is functionally related to phyB-mediated
      responses. However, in contrast to phyB-controlled seed germination, this phyX
      mediated response needs a prolonged imbibition period and exhibits reversibility
      kinetics different from that needed for phyB. Furthermore, this phyX response
      requires a prolonged irradiation time and shows a fluence rate response
      dependency, showing a similarity to the high irradiance response of
      photomorphogenesis. Thus, phyX, with regard to its control of seed germination,
      is a functionally new phytochrome that shares some characteristics of both phyA-
      and phyB-mediated responses.

PMID- 9276957
TI  - Expression and native structure of cytosolic class II small heat-shock proteins.
AB  - Higher plants synthesize small heat-shock proteins (smHSPs) from five related
      gene families. The class I and II families encode cytosolic smHSPs. We
      characterized the class II smHSPs of pea (Pisum sativum) and compared them with
      class I smHSPs. Antibodies against recombinant HSP17.7, a class II smHSP,
      recognized four heat-inducible 17- to 18-kD polypeptides and did not cross-react
      with class I smHSPs. On sucrose gradients the class II smHSPs sedimented
      primarily at 8 Svedberg units, indicating that they are components of large
      complexes similar in size to class I smHSP complexes. However, the class I and II
      complexes were readily distinguishable by nondenaturing polyacrylamide gel
      electrophoresis and isoelectric focusing. Nondenaturing immune precipitations
      using anti-HSP17.7 or anti-HSP18.1 (a class I smHSP) antiserum provide further
      evidence that the class I and II smHSPs exist in different complexes, composed
      primarily of smHSPs. Recombinant HSP17.7 and HSP18.1 formed complexes of sizes
      similar to those formed in vivo. When these two smHSPs were mixed, denatured with
      urea, and then dialyzed, the distinct class I and II complexes again formed, each
      containing only HSP18.1 or HSP17.7. Thus, cytosolic smHSPs from two related gene
      families expressed simultaneously form distinct complexes in vivo, suggesting
      that they have subtly different functions.

PMID- 9276959
TI  - Inositol 1,4,5-trisphosphate-sensitive Ca2+ release across nonvacuolar membranes
      in cauliflower.
AB  - Previous studies have indicated that the vacuole represents the major inositol
      1,4,5-trisphosphate (InsP3)-mobilizable Ca2+ pool in higher plants. This findings
      is in contrast to animal cells, in which the endoplasmic reticulum and plasma
      membrane constitute the dominant InsP3-sensitive membranes. We used membrane
      vesicles prepared from cauliflower (Brassica oleracae L.) inflorescences that
      were separated on continuous sucrose gradients to demonstrate that cauliflower
      possesses at least two distinct membrane populations that are sensitive to InsP3.
      One of these membrane populations in nonvacuolar in origin and relies upon a
      Ca(2+)-ATPase to accumulate Ca2+. In addition, we have shown that two polyclonal
      antibodies, raised against peptides corresponding to the animal type 1 InsP3
      receptor, recognize immunologically related proteins in cauliflower, and that the
      distribution of immunoreactive proteins on a linear sucrose gradient reinforces
      the notion that cauliflower contains more than one membrane subtype that is
      sensitive to InsP3. To our knowledge, this is the first report describing an
      InsP3-sensitive Ca2+ store other than the vacuole in higher plant cells.

PMID- 9276960
TI  - Overexpression of the FAD3 desaturase gene in a mutant of Arabidopsis.
AB  - A mutant of Arabidopsis contained increased levels of 18:3 fatty acids and
      correspondingly decreased levels of 18:2. The fatty acid phenotype was strongly
      expressed in root and seed tissues and this observation, together with other
      data, suggested that the mutation leads to increased activity of the endoplasmic
      reticulum 18:2 desaturase encoded by the FAD3 gene. Gel-blot analysis of RNA from
      wild-type and mutant plants established that FAD3 transcript levels were
      increased 80% in the mutant relative to the wild type. Genetic analysis
      demonstrated a linkage between the new mutation and the fad3 locus. Linkage of
      the mutation to fad3 raises the possibility that the lesion is an alteration to
      the promoter or another regulatory region of the FAD3 gene, which results in
      increased transcription.

PMID- 9276961
TI  - Immunodetection and characterization of tomato endo-beta-1,4-glucanase Cel1
      protein in flower abscission zones.
AB  - Tomato (Lycopersicon esculentum Mill.) endo-beta-1,4-glucanase Cel1 mRNA
      accumulation was previously correlated with abscission of flower explants. Cel1
      antibodies were raised against a fusion protein encoding a portion of the Cel1
      polypeptide and was shown to react specifically with three polypeptides with
      molecular masses ranging between 51 and 53 kD in flower abscission zones induced
      to abscise. All three polypeptides were clearly suppressed in two transgenic
      lines expressing an antisense Cel1 gene that specifically suppressed the
      accumulation of Cel1 mRNA, indicating that all three polypeptides are products of
      the Cel1 gene. Cel1 protein accumulation was correlated with flower abscission.
      Breakstrength and Cel1 protein content were also analyzed in flower explants,
      indicating that Cel1 protein accumulation is correlated with the final stages of
      flower shedding, which suggests that Cel1 is involved in the late stage of
      abscission. These results support the involvement of Cel1 in the abscission of
      flower explants and suggest that other hydrolase activities also participate in
      that process.

PMID- 9276962
TI  - Characterization and functional expression of a ubiquitously expressed tomato
      pectin methylesterase.
AB  - Pectin methylesterase (PME), a ubiquitous enzyme in plants, de-esterifies the
      methoxylated pectin in the plant cell wall. We have characterized a PME gene
      (designated as pmeu1) from tomato (Lycopersicon esculentum) with an expression
      that is higher in younger root, leaf, and fruit tissues than in older tissues.
      Hypocotyls and epicotyls show higher accumulation of pmeu1 transcripts compared
      with cotyledons. pmeu1 represents a single-copy gene in the tomato genome.
      Comparison of the deduced amino acid sequence of pmeu1 with other PME homologs
      showed that the N-terminal halves are highly variable, and the C-terminal halves
      are relatively conserved in plant PMEs. Constitutive expression of a fruit
      specific PME antisense gene does not affect the level of pmeu1 transcripts in
      vegetative tissues but does lower the level of PMEU1 mRNA in developing tomato
      fruits. These results suggest that there exists developmentally regulated
      silencing of pmeu1 by a heterologous PME antisense gene. Expression of pmeu1 in
      tobacco (Nicotiana tabacum) under the control of the cauliflower mosaic virus 35S
      promoter caused up to a 4-fold increase in PME specific activity that was
      correlated with the accumulation of PMEU1 mRNA. In vitro transcription
      translation analyses show that pmeu1 encodes a 64-kD polypeptide, whereas
      transgenic tobacco plants expressing pmeu1 accumulate a new 37-kD polypeptide,
      suggesting extensive posttranslational processing of PMEU1. These results are the
      first evidence, to our knowledge, of the functional characterization of a PME
      gene and the extensive modification of the encoded polypeptide.

PMID- 9276963
TI  - Convergence of the abscisic acid, CO2, and extracellular calcium signal
      transduction pathways in stomatal guard cells.
AB  - We show that guard cells from Arabidopsis thaliana plants carrying the abscisic
      acid-insensitive mutations abi1 and abi2 fail to respond to CO2 and extracellular
      calcium. This demonstrates that the signal transduction pathways for all three
      stimuli converge on, or close to, the ABI1 and ABI2 gene products.

PMID- 9276965
TI  - The role of nitrogenase in a cyanide-degrading Klebsiella oxytoca strain.
AB  - It is well known that the major function of nitrogenase is to fix atmospheric
      nitrogen. However, cyanide can also serve as a subtrate for nitrogenase and can
      be reduced to CH4 and NH4+. A cyanide-degrading Klebsiella oxytoca strain was
      isolated from cyanide contaminated water. This isolate was also found to have a
      nitrogen-fixation capability. Nitrogenase activities in this organism could be
      induced by KCN. However, there was no significant difference of the induction
      effect between 1 mM KCN and 5 mM KCN. It was found that the cyanide-degrading
      ability of this isolate could be inhibited by multicopy hybrid pGR112 nif
      containing plasmids. Comparing the wild type K. oxytoca strain with the pGR112
      plasmid transformed strain, a typical diauxic growth of the wild type strain was
      observed in a medium containing NH4Cl and KCN. Although the nif plasmid
      transformed strain also exhibited diauxic growth in the same medium, a much
      longer second lag phase was noted. In addition, methane, the nitrogenase
      reduction end product of cyanide, could be detected on cyanide-containing growth
      cultures. Ammonium chloride, a repressor of nitrogenase gene expression, was
      consumed prior to KCN in both strains. Again, the degradation of KCN in the
      pGR112 transformed strain occurred only under loose control of the nitrogenase
      gene. These findings strongly suggest that nitrogenase may be the sole cyanide
      degrading enzyme in this organism.

PMID- 9276964
TI  - Mechanosensitive expression of a lipoxygenase gene in wheat.
AB  - Touch stimulation of wheat (Triticum aestivum L.) seedlings led to a strong and
      dose-dependent increase in the level of lipoxygenase mRNA transcripts. The touch
      induced response occurred within 1 h and was transient. A similar response was
      observed after wind treatment and wounding. The mechanical strain-regulated
      lipoxygenase might translate mechanical strain into lipoxygenase pathway
      dependent growth responses.

PMID- 9276966
TI  - Silver-binding nucleolar organizer regions in hepatolithiasis and bile duct
      cancer.
AB  - Hepatolithiasis and bile duct cancer have usually been linked together especially
      in Asian countries. Epithelium cells of bile duct or ductal glands had
      proliferative changes in patients with hepatolithiasis usually. The numbers and
      shape of the nucleoli were studied with special staining of AgNOR (Nucleolar
      Organizer Regions) on bile ducts without calculi (n = 11), with calculi (n = 21),
      and hepatolithiasis with bile duct carcinoma (n = 14). The patterns of AgNOR were
      classified into a dotted type and a cluster type under light microscopic
      examination. AgNORs scores were found to be 2.7 +/- 1.2 (M +/- SD) and 3.6 +/-
      1.2 for intramural glandular cells and extramural glandular cells in
      hepatolithiasis (p < 0.05). In the cases of bile duct carcinoma, the percentage
      of the cluster form of AgNOR was 28.1 +/- 4.4%, and the scores were 4.7 +/- 2.4
      for bile duct cancer, which was significantly different from intramural glands,
      but not different from the extramural glands in hepatolithiasis. High scores of
      the dotted type and high percentage of cluster type have high potentiality of
      malignant changes. From this study, unknown substances for malignant
      transformation might be secreted from the inner epithelium and or intramural
      glandular epithelium both of which are usually in contact with the infected bile
      and have chronic irritation from the stones. Extramural glands of the bile duct
      had higher potential for proliferation or malignant transformation in our study.
      Hence, long-term follow-up study of those patients with hepatolithiasis should be
      done very carefully especially due to the possibility of a combination of
      neoplastic changes in hepatolithiasis.

PMID- 9276967
TI  - Hormonal changes associated with menstrual cycle have no definite influence on
      ocular pressure.
AB  - BACKGROUND: Despite some findings to the contrary, it would appear that
      pharmacological doses of progesterone and estrogen (alone or in combination) can
      influence intraocular pressure (IOP). The relationship between hormonal changes
      associated with the menstrual cycle and intraocular pressure is not clearly
      understood. After elimination of those factors that can affect IOP, the present
      study investigated whether physiological hormonal changes associated with the
      menstrual cycle have a correlation with intraocular pressure. METHODS:
      Intraocular pressure and the concentrations of circulating hormones, namely, the
      luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrone (E1),
      estradiol (E2), progesterone, and testosterone, of twenty married women of the
      same age groups were recorded daily throughout a menstrual cycle. None was taking
      any contraceptives in any form. The intraocular pressure was measured using a
      Goldmann applanation tonometer. RESULTS: The intraocular pressure values
      fluctuated in each of the twenty subjects at various times of the cycle; however,
      they were not definitely correlated with the different phases of the cycle. This
      study failed to find any correlation between IOP and progesterone or estradiol
      levels.

PMID- 9276968
TI  - Identification of classic and complex t(15;17) and/or RAR alpha/PML gene fusion
      in APL by cytogenetic and dual color-FISH techniques.
AB  - Acute promyelocytic leukemia (APL) is a malignant condition characterized by
      t(15;17)(q22;q12), which fuses the PML gene on chromosome 15 to the retinoic acid
      receptor alpha (RAR alpha) gene on chromosome 17. In this study, t(15;17) was
      identified cytogenetically by using the conventional cytogenetic technique, and
      its molecular counterpart RAR alpha/PML fusion on chromosome 17 on interphase
      nuclei was further confirmed by means of dual color- (DC-) fluorescence in situ
      hybridization (FISH) on serial bone marrow (BM) and peripheral blood (PB) samples
      from APL patients at different stages of the disease. Overall, our findings
      indicate that interphase DC-FISH analysis can be a useful technique as an adjunct
      to conventional cytogenetic investigation for detecting the presence of RAR
      alpha/PML fusion in APL.

PMID- 9276969
TI  - Application of dipole modeling in localization of mesio-temporal epileptogenic
      focus.
AB  - Improved methods for noninvasive localization of an epileptic focus, modeled as
      an electrical dipole, are developed in this research. For the head geometrical
      model, a three-dimensional (3-D) electromagnetic tracking system is utilized to
      measure the exact positions of electrodes. A nonlinear optimization technique,
      the Levenberg-Marquardt method, is adopted for dipole localization. For the
      optimization algorithm to converge to correct solution, the singular value
      decomposition (SVD) technique is used to extract the dominant component of the
      EEG spike for initial estimation and dipole localization. The localization
      results of varied montages, including standard 10-20 electrodes and enhanced
      temporal electrodes, with or without invasive sphenoid electrodes, are compared.
      Our experimental results indicate that dipole localization with enhanced temporal
      electrodes can be used as an alternative for the invasive sphenoid electrodes to
      differentiate the epileptogenic foci of mesio-temporal area from temporal
      convexity.

PMID- 9276970
TI  - Production of chitinase from shellfish waste by Pseudomonas aeruginosa K-187.
AB  - The production of chitinolytic enzyme by Pseudomonas aeruginosa K-187, using
      shrimp and crab shell powder (SCSP) as the carbon source, was studied. It was
      observed that chemically treated SCSP induced a significant increase of enzyme
      production, as compared with untreated SCSP. Spent HCl and NaOH from the chitin
      production industry was used to process SCSP. Various strategies of SCSP
      processing are examined and compared in terms of chitinolytic enzyme production.
      A three-and-one-half-fold increase of enzyme production (0.68 U/ml to 2.4 U/ml)
      was attained using HCl/NaOH treated SCSP. The microorganism (K-187) was isolated
      from soil in Taiwan and has been characterized and reported in a previous paper.

PMID- 9276971
TI  - Integrated multichannel microchip electrospray ionization mass spectrometry:
      analysis of peptides from on-chip tryptic digestion of melittin.
AB  - In continuation of our work to develop an integrated multichannel microchip
      interfaced to electrospray mass spectrometry (ESI-MS), this paper demonstrates
      one of several applications of this approach in monitoring tryptic digestion
      products. The multichannel microchip allowed integration of sample preparation
      onto the microchip to facilitate the analysis process. Melittin was selected as a
      model oligopeptide because it possesses a cluster of four adjacent basic residues
      which enable probing the site specificity of trypsin as a function of digest
      times. Reactions were performed on-chip in different wells for specific time
      periods and then analyzed by infusion from the microchip by ESI-MS, using leucine
      enkephalin as internal standard. The rate of formation and disappearance of the
      molecular ion and individual fragments was followed for a melittin to trypsin
      concentration ratio of 300:1. The results indicate the potential of integrating
      enzymatic reactions with multichannel microchip ESI-MS for automated optimization
      of reaction condition while consuming only small amounts of sample.

PMID- 9276973
TI  - Separation and characterization of the tryptic peptide mapping of recombinant
      bovine growth hormone by reversed-phase high-performance liquid chromatography
      electrospray mass spectrometry.
AB  - Reversed phase high-performance liquid chromatography (RPHPLC) coupled with
      electrospray ionization mass spectrometry (ESI-MS) was used to separate and
      characterize the peptides resulting from the tryptic cleavage of somidobove, a
      recombinant bovine growth hormone. The tryptic digestion of somidobove was
      carried out at room temperature for 15 hours. The tryptic peptides were separated
      on a Zorbax SB300 C8 column with trifluoroacetic acid--acetonitrile gradient
      elution and characterized by LC/ESI-MS. Resulting single and combined peptide
      fragments were characterized by comparing the observed molecular mass with the
      calculated mass for these fragments.

PMID- 9276972
TI  - Identification of the glycosylation site and glycan structures of recombinant
      endopolygalacturonase II by mass spectrometry.
AB  - A series of mass spectrometric experiments was performed to characterize the
      carbohydrate chains attached to endopolygalacturonase II (EPG-II) overexpressed
      in Aspergillus niger. First, an aliquot of trypsin-digested EPG-II was analyzed
      by capillary high-performance liquid chromatography (HPLC) coupled with
      electrospray ionization (ESI) mass spectrometry (HPLC/MS). The ESI mass
      spectrometer was operated in the tandem mass spectrometric (MS/MS) mode and
      utilized precursor ion scanning of the HexNAc+ oxonium ion at m/z 204 to
      selectively detect glycopeptides eluting from the HPLC. Aliquots of the fraction
      identified by HPLC/MS/MS to contain a glycopeptide were then sequentially
      digested with Aspergillus saitoi alpha-1-2-mannosidase and peptide N:glycosidase
      F (N-glycanase), followed by matrix-assisted laser-desorption/ionization mass
      spectrometric analysis to provide structural information from the carbohydrate
      chain. The masses of the carbohydrate chains in the glycopeptides were thus
      determined and subsequently used to search the Complex Carbohydrate Structure
      Database for the probable structures of the glycans. This analysis determined
      that recombinant EPG-II has a single N-glycosylation site, the carbohydrate chain
      at this site is heterogeneous, and the glycan structure is of the high-mannose
      type. No sites of O-glycosylation were detected in EPG-II.

PMID- 9276974
TI  - On-line derivatization of peptides for improved sequence analysis by micro-column
      liquid chromatography coupled with electrospray ionization-tandem mass
      spectrometry.
AB  - An on-line method has been developed for the derivatization and coupled liquid
      chromatography (LC)/electrospray ionization (ESI) MS analysis of peptides at the
      femtomol level. Peptides are reacted with N-succinimidyl-2(3-pyridyl)acetate
      (SPA) in buffered aqueous medium at pH7 following loading on a precolumn (PC) in
      a microcolumn switching system. The fast-hydrolysing reagent is dissolved in dry
      methanol and mixed, in a 3 vol% ratio, with a buffer just before reaching the
      sample on the PC. Following the reaction and wash, the N-pyridylacetyl (PA)
      derivatives formed are transferred to the analytical micro-high-performance (HP)
      LC column for separation and subsequent ESI tandem MS analysis. The reaction is
      nearly quantitative and takes place selectively at the N-terminal and lysine
      amino functions, the latter providing a chemical means to distinguish between
      isobaric residues lysine and glutamine. In some cases, a minor reaction was
      observed with the tyrosine hydroxyl group. The N-terminal PA group was able to
      alter the collision-induced fragmentation pathway of peptides in favour of the
      formation of abundant b-type ions, a helpful feature for sequence elucidation of
      unknown peptides, particularly with quadrupole ion trap instruments.

PMID- 9276975
TI  - Rapid separation and characterization of protein and peptide mixtures using 1.5
      microns diameter non-porous silica in packed capillary liquid chromatography/mass
      spectrometry.
AB  - Octadecyl-modified 1.5 microns diameter non-porous silica particles were packed
      in 150 microns i.d. (360 microns o.d.) capillaries with lengths of 20 cm which
      were used to separate proteins and peptides generated from enzymatic digests of
      proteins. Gradients were produced using an exponential dilution method at
      pressures of 520 Bar (7500 psi) and electrospray ionization mass spectrometry was
      used for detection. This system was similar to packed capillary perfusion
      chromatography with respect to chromatographic resolution and analysis time and
      had a limit of detection comparable to traditional packed capillaries which use 5
      microns diameter porous particles. The analyses required as little as 250
      femtomol of protein or 500 femtomol of peptide on-column in approximately 30 min.
      This technique was then applied to verify the existence of an overexpressed
      protein in an E. coli cell lysate and to confirm the presence of four glycoforms
      of a peptide generated in the proteolytic digest of an antibody.

PMID- 9276976
TI  - Key fragmentations for the interpretation of mass spectra of disubstituted bile
      acids of bovine and porcine origin.

PMID- 9276977
TI  - Analytical strategies in the structural characterization of elcatonin.
AB  - Elcatonin is a synthetic peptide of 32 amino acid residues, that differs from
      natural peptide hormone (eel calcitonin) in that the 1 and 7 cystine residues are
      replaced with alpha-amino suberic acid (Asu). Elcatonin is pharmacologically
      important, since it inhibits osteoclastic bone reserption and induces calcium
      uptake from body fluids. It is also used for the treatment of Page's disease and
      hypercalcemic conditions. Until now the structural characterization of elcatonin
      has been obtained by proteolytic digestion followed by high performance liquid
      chromatographic (HPLC) analysis of the peptide fragments. Capillary
      electrophoresis and fast-atom bombardment have also been employed. This work
      describes the results obtained when a liquid chromatograph, coupled to mass
      spectrometer using electrospray ionization (LC/ESI-MS) was applied to elcatonin
      analysis. After digestion with trypsin, the resulting peptides were separated by
      HPLC with 'on-line' UV detection, and directly injected into the ESI source. The
      molecular weights of all the fragments were detected, and the sequences of two of
      them were determined by collisionally induced dissociation in the ESI source. To
      confirm these 'on-line' results, the 'off-line' approach was also applied. In
      this case, the fragments from tryptic digestion were isolated by preparative
      HPLC, concentrated and analyzed by direct infusion into the ESI-MS system. Then,
      different elcatonin digests obtained using other proteases, e.g. protease V8 and
      clostripain, were analyzed by direct infusion, and these results combined with
      those achieved by the 'on-line' analysis allowed us to obtain the entire mapping
      of elcatonin.

PMID- 9276978
TI  - Evaluation of IgG glycation levels by matrix-assisted laser desorption/ionization
      mass spectrometry.
AB  - Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry has been
      employed for the evaluation of the glycation level of IgG from healthy subjects
      and also from well- and badly-controlled diabetic patients. The measurements have
      been performed on untreated plasma protein fractions. The data obtained have
      shown that a clear mass increase, originating from non-enzymatic glycation
      processes, is observed in the case of diabetic patients: for well-controlled ones
      it is in the range 512-1565 Da, while it becomes 827-4270 Da for badly-controlled
      diabetic patients. This approach indicates that MALDI mass spectrometry is a
      highly specific tool that can be employed in the metabolic control of diabetic
      patients and in studies relating the IgG glycation level to possible
      immunological impairment.

PMID- 9276982
TI  - 24(24(1))[Z]-dehydroamarasterone B, a phytoecdysteroid from seeds of Leuzea
      carthamoides.
AB  - A new phytoecdysteroid, 24(24(1))[Z]-dehydroamarasterone B, has been isolated
      from seeds of Leuzea (Rhaponticum) carthamoides. It has been unambiguously
      identified by CIMS, 13C NMR and 1H NMR spectroscopy. The biological activity of
      the ecdysteroid has been determined in the Drosophila melanogaster BII bioassay.
      The ED50 (5.2 x 10(-7) M) is 70-fold higher than that for 20-hydroxyecdysone (7.5
      x 10(-9) M).

PMID- 9276981
TI  - Antimicrobial compounds from Ceanothus americanus against oral pathogens.
AB  - During the search for antimicrobial compounds from higher plant sources, a
      methanol extract of Ceanothus americanus demonstrated antimicrobial activity
      against selected oral pathogens. Through further bioassay-guided fractionation
      and purification, three triterpenes (ceanothic acid, 27-hydroxy ceanothic acid
      and ceanothetric acid) and two flavonoids (maesopsin and maesopsin-6-O-glucoside)
      were identified. Among these, ceanothetric acid and maesopsin-6-O-glucoside were
      new compounds. Ceanothic acid and ceanothetric acid demonstrated growth
      inhibitory effect against Streptococcus mutans, Actinomyces viscosus,
      Porphyromonas gingivalis, and Prevotella intermedia with MICs ranging from 42 to
      625 micrograms ml-1. Maesopsin, its glucoside, and 27-hydroxy ceanothic acid,
      were inactive below the concentration of 500 micrograms ml-1.

PMID- 9276983
TI  - Hydroxylation of dehydroabietic acid by Fusarium species.
AB  - A novel compound, 1 beta-hydroxydehydroabietic acid has been obtained by the
      microbial transformation of dehydroabietic acid, using cultures of Fusarium
      oxysporum and F. moniliforme. Its antibacterial activity was also tested.

PMID- 9276985
TI  - The structure and function of the avian immune system.
AB  - Among the avian species, the immune system of the chicken has been studied most
      extensively. There are many similarities between the general immune mechanisms of
      mammals and chickens. There are also important differences. Birds respond to
      antigenic stimulation by generating antibodies as well as cellular immunity.
      There are three principal classes of antibodies in birds i.e., IgM, IgG (also
      called IgY) and IgA. Antibody diversity is achieved by gene conversion. T cells
      are the main effector cells of cellular immunity. The avian T cells differentiate
      into two distinct pathways i.e., alpha/beta and gamma/delta. Avian T cell
      diversity is likely generated through combinatorial and junctional mechanisms
      similar to the mechanisms that operate in mammalian T cell receptors. As in
      mammals, avian T cells engage in helper and cytotoxic functions that are MHC
      restricted. The innate effector mechanisms include those mediated by natural
      killer (NK) cells and antibody dependent cellular cytotoxicity (ADCC). Recently,
      genes of several avian cytokines have been cloned and expressed. A number of
      naturally occurring viruses cause immunosuppression in chickens. There is much
      current interest in understanding the mechanisms of immunosuppression and
      developing strategies to enhance immune responsiveness in commercial poultry.

PMID- 9276986
TI  - Viral diseases of the immune system and strategies to control infectious bursal
      disease by vaccination.
AB  - Viral infections which are immunosuppressive can affect the economics of poultry
      production, often as a result of the chicken's increased susceptibility to
      secondary infections and sub-optimal response to vaccinations. The mechanism of
      this immunosuppression has been studied in detail for certain chicken viruses.
      The replicating virus can have both direct and indirect effects on the cells of
      the immune system. The special role of the bursa of Fabricius, as a lympho
      epithelial organ, will be mentioned. The effects of oncogenic viruses (MDV, REV
      and ALV) on the immune system will be discussed as will the present status of our
      knowledge on the immunosuppressive effects of certain respiratory viruses such as
      ILT, NDV and reovirus. Two major immunosuppressive agents are CAV and IBDV. The
      effects of IBDV will be described in more detail because of its economic
      importance. Advances made in the molecular biology of both the virus and the
      immune system give new opportunities to control the disease by vaccination.
      Successful vaccination strategies applied in the past and options for the future
      will be discussed.

PMID- 9276987
TI  - Avian tumor viruses: persistent and evolving pathogens.
AB  - Most neoplasias of lymphoid and other hematopoietic cells in commercial poultry
      are caused by viruses which belong to one of four distinct groups. Marek's
      disease virus (MDV) is an oncogenic herpesvirus. Avian leukosis virus (ALV),
      reticuloendotheliosis virus (REV) and lymphoproliferative disease virus (LPDV)
      are oncogenic retroviruses. Each group is distinguished by nucleic acid type,
      molecular structure, antigenicity, epidemiology, host range and other
      characteristics. However, most of these viruses have in common a unique ability
      to persist, both in the host and in the ecosystem. In addition, both the viruses
      and the virus-host relationships for several members of the group have
      demonstrated a propensity to evolve with time, creating new dilemmas for
      diagnosis and control. A focus on the persistence and evolution of avian tumor
      viruses will be used to address a number of current issues with individual
      viruses of economic importance. Issues of primary concern include (1) the
      evolution of MDV towards greater virulence with concomitant reduction of vaccine
      efficacy and expansion of host range, (2) the emergence of subgroup J ALV as a
      major pathogen in meat-type breeder stocks, and (3) the increasing prevalence of
      REV and its evolving role as a pathogen in chickens and turkeys.

PMID- 9276988
TI  - Epidemiology of avian diseases.
AB  - A large number of diseases occur in domestic, farm-raised poultry. Only two of
      the many different diseases are notifiable and subject to governmental control:
      highly pathogenic avian influenza and Newcastle disease. Diagnosis and treatment
      or prevention of all other conditions are left to the skills of farmers and their
      veterinarians. Poultry production is aimed at providing more and tastier food for
      the ever growing human community. Infectious diseases and technical errors during
      production and processing need to be minimised. The concept of hazard analysis
      critical control point (HACCP) has already been introduced into food processing
      and quality assessment. The regulations laid down in ISO 9000 will soon become a
      powerful and practical tool for monitoring and improving the productivity of live
      poultry. Approved epidemiological concepts and tools will enable the poultry
      industry to achieve constant and safe production. Certification on the basis of
      ISO 9000 of all areas of poultry production is a new approach for maintaining the
      health of poultry, for tracing and subsequently eliminating breaks in
      productivity, and securing production without health hazards for the consumer.

PMID- 9276989
TI  - Towards the routine application of nucleic acid technology for avian disease
      diagnosis.
AB  - The use of nucleic acid technology (polymerase chain reaction, probing,
      restriction fragment analysis and nucleotide sequencing) in the study of avian
      diseases has largely been confined to fundamental analysis and retrospective
      studies. More recently these approaches have been applied to diagnosis and what
      one might call real-time epidemiological studies on chickens and turkeys. At the
      heart of these approaches is the identification and characterisation of pathogens
      based on their genetic material, RNA or DNA. Among the objectives has been the
      detection of pathogens quickly combined with the simultaneous identification of
      serotype, subtype or genotype. Nucleic acid sequencing also gives a degree of
      characterisation unmatched by other approaches. In this paper we describe the use
      of nucleic acid technology for the diagnosis and epidemiology of infectious
      bronchitis virus, turkey rhinotracheitis virus (avian pneumovirus) and Newcastle
      disease virus.

PMID- 9276990
TI  - Changing expectations in the control of Mycoplasma gallisepticum.
AB  - Mycoplasma gallisepticum (MG) is traditionally controlled by maintaining MG-free
      flocks on single-age production sites and maintaining them MG-free utilizing good
      biosecurity and a consistent serological monitoring program. In recent years,
      several changes have taken place which have changed our ways about thinking about
      MG control. There have been significant improvements in detection methods. For
      example, polymerase chain reaction now represents a rapid and sensitive method
      for detecting the organism. ELISA kits are now much improved. DNA technology now
      allows rapid identification of specific strains (DNA finger-printing) for
      epidemiological studies. On the other hand, the industry world-wide is growing
      rapidly, and there are huge populations of poultry in small geographic areas,
      making control utilizing biosecurity more and more difficult. Also, multi-age
      production sites are becoming more common, especially in commercial egg
      production. This has led to increased usage of live MG vaccines, which are
      effective in controlling economic losses and may be used as tools in eradication
      programs.

PMID- 9276991
TI  - Safe poultry meat production in the next century.
AB  - The revolutionary industrialisation of the poultry industry in the last 30 years
      has made the food poultry meat available for large groups of consumers. Due to
      its nutritional, sensory and economical characteristics, poultry meat is by far
      the most popular animal food product world-wide. Epidemiological reports,
      however, incriminate poultry meat as a source for outbreaks of human food
      poisoning. The organisms involved are Salmonella spp., Campylobacter spp. and, to
      a lesser extent, Listeria monocytogenes, Escherichia coli, Staphylococcus aureus,
      Yersinia enterocolitica, Clostridium perfringens and Aeromonas spp. Contamination
      of the end-product with pathogenic microorganisms is a reflection of the
      contamination of the live birds and, therefore, measures to be taken by industry
      to avoid contamination of the consumer-ready product should start at that level.
      In terms of the critical control point approach of the HACCP concept, the
      quantitative contribution of critical phases in the production chain towards end
      product contamination should be estimated in order to take the necessary
      intervention or corrective steps. To guarantee the production of safe poultry
      meat, knowledge of the capability of microorganisms to colonise the
      gastrointestinal tract is needed and the use of vaccines, antimicrobials and
      competitive exclusion microfloras as well as the implementation of new processing
      technology should be encouraged.

PMID- 9276992
TI  - Novel approaches to control of bacterial infections in animals.
AB  - Bacterial infections of poultry remain of great importance world-wide in terms of
      economic effects and public health. They include infections caused by Salmonella,
      Escherichia coli, Campylobacter and Pasteurella. Through the introduction of
      rigid hygienic measures it is possible to breed and rear poultry free of these
      pathogens. However, the cost to the industry would be prohibitive and
      economically disastrous. Biological measures have been introduced albeit in a
      relatively empirical way. Antibiotic therapy and prophylaxis is used extensively
      with the associated problems of development of resistance. Killed vaccines are
      used but are not usually very effective. Live vaccines are increasingly becoming
      acceptable and studies are under way to increase our understanding of the
      pathogenesis of these infections so that vaccine development may become less
      empirical. Work with live vaccines to be used against Salmonella has shown that
      they may be administered orally to newly-hatched chicks. The vaccine strain
      colonises the gut extensively and prevents re-infection by other Salmonella
      strains by a genus-specific mechanism which is similar to that which occurs
      during down-regulation of bacterial growth in stationary-phase nutrient broth
      cultures. The mechanism of this phenomenon is currently being studied. This
      approach may also be applied to control Campylobacter infections. Bacteria of the
      Pasteurella group and E. coli may produce septicaemic infections in poultry.
      Recent work with K1+ E. coli infections in mice has shown that virulent
      bacteriophages may be used to treat or prevent septicaemias and meningitides.
      This work has been extrapolated to chickens with a similar degree of success and
      it suggests that some infections of this sort in animals and man may be amenable
      to this approach. In-bred lines of chickens have been found to vary greatly in
      their susceptibility to systemic Salmonella infections. This is probably mediated
      by one gene and the effect is dominant and not linked to sex or MHC. The mouse
      natural resistance gene (NrampI) does not appear to contribute greatly to this
      effect. Differences in the extent of gut colonisation by Salmonella in in-bred
      and out-bred lines can also be detected. These results are very exciting and open
      up opportunities for disease control for the future.

PMID- 9276993
TI  - Eimeria spp. from the chicken: occurrence, identification and genetics.
AB  - Many fundamental aspects of the biology of Eimeria spp. from the chicken remain
      poorly understood and some have not been investigated in detail for many years.
      New molecular tools are now available that could be used to underpin some of the
      more practical aspects of disease control. For example, a far better
      understanding of the epizootiology of the parasites, with precise knowledge of
      the characteristics of individual species and strains that are prevalent in the
      field might, in the future, be incorporated into strategies that see a more
      rational use of the available drugs and vaccines. The recent use of
      electrophoretic variation of enzymes to investigate parasite epizootiology is
      described and the general case for the development of specific, more sensitive
      DNA-based technologies is discussed. A wealth of DNA probes is potentially
      available from the large genome of Eimeria spp. and the genetic complexity of
      these parasites has recently been illustrated in more detail. In addition to a
      large nuclear genome comprising at least 14 linear chromosomes, studies on E.
      tenella have shown that, like Plasmodium and Toxoplasma, it also possesses a
      mitochondrial genome and a newly discovered "plant-like" genome that probably
      resides within an uncharacterised organelle and was acquired when an ancestor
      engulfed and kept and algal cell containing a chloroplast. A double-stranded RNA
      genome has also been identified in some species.

PMID- 9276994
TI  - Nutritional metabolic diseases of poultry and disorders of the biological
      antioxidant defence system.
AB  - Deficiencies or disturbances of nutrition cause a variety of diseases and can
      arise in different ways. The amount of a particular nutrient in the diet may be
      insufficient to meet the requirements, the diet may contain substances that
      inactivate the nutrient or inhibit its absorption/utilisation, or metabolism may
      be upset by the interaction of dietary and environmental factors. Peroxidation of
      lipids or oxygen free radical generation in general is a physiological process
      important for cell metabolism, division and differentiation and also for the
      biosynthesis of hormones and prostaglandins. Free radicals generated through
      these processes are effectively scavenged by the antioxidant defence system.
      Uncontrolled lipid oxidation caused by disturbances of that system may play a
      crucial role in some important poultry diseases and toxicoses. The first route of
      lipid peroxide loading of the organism is via the feed, such as through oxidised
      lipids. Oxidised fatty acids are absorbed from the intestine mainly in the form
      of unsaturated keto compounds and initiate lipid peroxidation in the tissues. The
      second problem is the insufficient amount of antioxidants in the feed, e.g.
      vitamin E deficiency. Nutritional encephalomalacia is a problem in poultry
      production which depends both on the actual vitamin E supply and the dietary
      amount of polyunsaturated fatty acids. In young birds the primary target of
      vitamin E deficiency is the brain because it contains low amounts of vitamin E,
      and the vitamin E content of the liver acting as store decreases rapidly during
      the first week of life. Besides vitamin E, other components of the antioxidant
      system, e.g. the antioxidant enzymes (catalase and glutathione peroxidase) also
      have low activity in the brain as compared to other major tissues. The brain is
      highly susceptible to oxidative stress because of the accumulation of
      polyunsaturated fatty acids. The third source of free radical generation is the
      toxic level of different feed ingredients, e.g. toxicoses caused by vitamin A,
      selenium, and ionophore antibiotics. Other important aspects of antioxidants
      (e.g. vitamin E and selenium) in poultry are stimulation of the immune response
      (e.g. in the case of vaccination) and reduction of the risks of free radical
      formation as a result of macrophage function.

PMID- 9276995
TI  - Biosecurity in poultry production: where are we and where do we go?
AB  - An overview is given about the importance of biosecurity in the poultry industry,
      and a comparison is made with other systems of disease control such as
      vaccination and medication. Different measures considered to be important in bio
      security are reviewed and some expectations for the future are given.
      Furthermore, some attention is paid to the animal welfare aspects.

PMID- 9276996
TI  - DNA amplification methods for diagnosis and epidemiological investigations of
      avian mycoplasmosis.
AB  - Rapid, sensitive and specific tests that detect nucleic acid from pathogenic
      mycoplasmas are very attractive for the laboratory detection of infected flocks,
      and methods for direct detection of the four main pathogenic mycoplasmas have
      been developed. Moreover, most avian mycoplasma species can be differentiated,
      according to their unique restriction fragment length polymorphism (RFLP)
      patterns generated with different restriction enzymes. However, this method is
      limited to the identification of pure cultures of avian mycoplasmas as other
      bacteria may be amplified by the set of primers chosen. Another application of
      PCR-RFLP is the ability to distinguish between very closely related species such
      as M. gallisepticum and M. imitans. In order to characterise isolates below the
      species level, PCR-based subtyping methods have been introduced. One of them,
      arbitrarily primed-PCR, results in strain-specific arrays of DNA fragments that
      can distinguish even closely related strains of a given species. This method was
      successfully used to investigate the molecular epidemiology of vaccine strains or
      of Mycoplasma gallisepticum conjunctivitis in songbirds. Major issues in the
      development of DNA amplification tests concern the selection of the appropriate
      target for amplification, specimen collection, DNA preparation and detection of
      amplification reaction inhibitors. Detection of amplified products is most
      commonly performed after gel electrophoresis or probe-based methods. Careful
      consideration to the design and work flow of the facility are necessary to avoid
      false-positive results.

PMID- 9276997
TI  - [Drug interaction].

PMID- 9276998
TI  - [Recent progress in cytokine signal transduction].

PMID- 9276999
TI  - [Comparison of predictive methods of Sugi (Cryptomeria) atmospheric pollen counts
      using mean temperature, solar radiation and male flowering index--an example of
      Toyama Prefecture].
AB  - The previous years mean temperature of July, total solar radiation of July and
      August and the male flowering index were used to predict atmospheric pollen
      counts. We examined the adaptability of these predictions and we get following
      results: 1. Following good harvest years of male flower, atmospheric pollen
      counts predicted by previous year's mean temperature of July and the total solar
      radiation of July and August are higher than the actual atmospheric pollen count.
      2. Prediction of atmospheric pollen counts by factors within the previous five
      years are more exact because matured Cryptomeria forests are increasing yearly.
      3. There are few errors in prediction by the flowering index because the flower
      index reflects the actual harvest of male flower.

PMID- 9277000
TI  - [Role of neutrophil elastase in allergen-induced airway microvascular leakage in
      sensitized guinea pigs].
AB  - To determine the role of neutrophil elastase in allergen-induced airway
      microvascular leakage, we assessed vascular permeability of guinea pig trachea by
      measuring the extravasation of Evans blue dye in the circulating blood.
      Inhalation of ovalbumin (OA) to guinea pigs sensitized with OA caused Evans blue
      extravasation, indicating an increased microvascular permeability. Pretreatment
      with ONO-5046 a specific inhibitor of neutrophil elastase, inhibited OA-induced
      vascular leakage in a dose-dependent manner. Tracheal instillation of human
      neutrophil elastase likewise increased microvascular permeability, and this
      effect was almost completely abolished by ONO-5046. Challenge with OA increased
      the number of neutrophils and neutrophil elastase activity in the bronchoalveolar
      lavage fluid, and these effects were inhibited by ONO-5046. These results suggest
      that neutrophil accumulation into the airway and the subsequent release of
      neutrophil elastase may play a role in the airway microvascular leakage produced
      by antigen challenge.

PMID- 9277001
TI  - [Immunomodulation by TYB-2285 of Dermatophagoides farinae (Df) antigen-induced
      IFN-gamma and IL-4 production in lymphocytes from children with bronchial
      asthma].
AB  - Effect of TYB-2285 and its metabolites on immune responses by peripheral blood
      mononuclear cells (PBMC) from children with bronchial asthma was investigated.
      TYB-2285 and its metabolites have immunosuppressive activity for the
      proliferation by Df-stimulated patients' lymphocytes. Concanavalin A (Con A)
      activated peripheral blood mononuclear cells (PBMC) from the patients were not
      affected by the same treatment. The results indicate that TYB-2285 and its
      metabolites are capable of suppressing antigen-induced 3H-thymidine (3H-TdR)
      uptake but not the response induced by Con A. Interferon-gamma (IFN-gamma)
      production by Df-stimulated PBMC from patients with active asthma, which was
      lower than that of normal lymphocytes, were reversed beyond the levels of that in
      normal subjects. Thus reduced production of IFN-gamma by Df-stimulated patients'
      lymphocytes was increased by TYB-2285 and its metabolites in a dose-dependent
      manner. This phenomenon was not observed in lymphocytes from normal subjects.
      Furthermore, TYB-2285 inhibited IL-4 production induced by Df antigen in
      asthmatic patients' lymphocytes. Taken, together, TYB-2285 could work as a weak
      immunosuppressant to modify lymphocytes' responses to allergen in patients with
      bronchial asthma. These data underscore the potential benefit for the patients
      with bronchial asthma.

PMID- 9277002
TI  - [Psychological investigation on spa therapy in patients with bronchial asthma].
AB  - To evaluate the effects of complex spa therapy (swimming training in a hot spring
      pool + fango therapy + inhalation of iodine salt solution) on psychological
      factors, three psychological examinations; CMI (Cornell Medical Index), SDS (Self
      Rating Depression Scale) and CAI (Comprehensive Asthma Inventory); were given 25
      patients with bronchial asthma (10 male, 15 female, mean age 60 years), and the
      results of these examinations were compared before and after spa therapy. 1.
      Physical symptoms, respiratory system and CIJ symptoms by CMI were significantly
      improved after spa therapy, however the improvement of psychical symptoms was not
      significant. 2. In SDS, 11 of 25 patients showed more than 40 points, indicating
      depressive state. The number of such patients decreased from 11 to 2 and the mean
      SDS score significantly improved from 38.7 to 34.2 after spa therapy. 3.
      Conditioning, suggestion, fear of expectation, frustration, flight into illness,
      negative attitudes towards prognosis, and decreased motivation towards therapy by
      CAI were significantly reduced after spa therapy, with the reduction in negative
      attitudes towards prognosis and decreased motivation towards therapy being
      relatively large. Furthermore, CAI score, which is the average of the categories
      in CAI, was also significantly decreased from 37.9 to 28.4 after spa therapy.
      These results suggested that complex spa therapy improves psychological factors
      in patients with bronchial asthma.

PMID- 9277003
TI  - [Close positive correlation between the level of mite-specific lymphocyte
      proliferation and the percentage of peripheral blood eosinophils in infants with
      atopic dermatitis].
AB  - Eosinophils (Eo) are known to play a critical role in the chronic allergic
      inflammation, featuring pathologically in atopic dermatitis (AD), and the Eo
      percentage in the peripheral blood is elevated in AD infants (0 y) as well as in
      older AD children (3-15 y). In search of the most important factor in the
      increase of Eo percentage, we analyse the correlation between the level of Eo
      percentage in the peripheral blood and the levels of various allergy-related
      parameters. In AD infants, the level of Eo percentage was found to be correlated
      most strongly with the level of mite-specific lymphocyte proliferation expressed
      by S.I.F. (stimulation index measured by flow cytometry) (r = 0.88, p < 0.001).
      It also correlated significantly with the levels of serum IgE (r = 0.56, p <
      0.05), egg white-specific IgE-RAST (r = 0.64, p < 0.01) and egg white-specific
      S.I.F.(r = 0.59, p < 0.02), but not with the levels of mite-specific IgE-RAST or
      candida-specific S.I.F. On the contrary, the level of Eo percentage correlated
      most intimately with the levels of serum IgE (r = 0.73, p < 0.001) and mite
      specific IgE-RAST (r = 0.71, p < 0.001) in older AD children. These results
      suggest that mite-specific peripheral blood helper T lymphocytes, the
      proliferation of which is thought to be represented by S.I.F., play a more
      essential role in AD infants than in older AD children in the increase of Eo
      percentage in the peripheral blood.

PMID- 9277004
TI  - Inherited thrombophilia: memorandum from a joint WHO/International Society on
      Thrombosis and Haemostasis meeting.
AB  - Inherited thrombophilias are common disorders with a worldwide distribution,
      including antithrombin, protein C, and protein S deficiencies as well as
      resistance to activated protein C. Increased understanding of these disorders
      suggests that thrombophilia can arise from interaction between defective genes
      and environmental factors. WHO and the international Society on Thrombosis and
      Haemostasis (ISTH) discussed the problems of inherited thrombophilia at a joint
      meeting held in Geneva on 6-8 November 1995. The present article reports on the
      various possibilities for controlling the disorder and makes a series of
      recommendations for diagnosis, treatment, and research into the condition.

PMID- 9277005
TI  - Reasons for failure of breast-feeding counselling: mothers' perspectives in
      Bangladesh.
AB  - During the hospitalization in the Dhaka hospital of the international Centre for
      Diarrhoeal Disease Research, Bangladesh, of a group of partially breast-fed
      infants aged 1-12 weeks who had been admitted with acute diarrhoea, their mothers
      were individually counselled by breast-feeding counsellors to start exclusive
      breast-feeding. The counselling was repeated 1 week later at home, and the
      women's infant-feeding practices were evaluated 2 weeks after their infants had
      been discharged from hospital. A total of 25% of the mothers failed to breast
      feed exclusively despite having been counselled. The case studies of these
      mothers illustrate that although they generally complained about having
      "insufficient breast milk" various factors such as domineering grandmothers, lack
      of financial support by their husbands, too much housework, or disinterest
      contributed to their failure to breast-feed exclusively. While family support is
      essential for all lactating mothers, women with familial or financial problems
      require special attention and extra counselling sessions so that they can be
      helped to identify how to achieve and sustain exclusive breast-feeding.

PMID- 9277006
TI  - Dental caries among Australian Aboriginal, non-Aboriginal Australian-born, and
      overseas-born children.
AB  - Few studies have specifically compared the prevalence of dental caries among
      contemporary Australian Aboriginal and non-Aboriginal children. Historically,
      Aboriginal groups have had substantially fewer dental caries than non-Aboriginal
      peoples. More recently, however, this trend appears to have been reversed, with
      improvements in the oral health of non-Aboriginal children and a deterioration in
      that of Aboriginal children; this tendency has important implications for dental
      health services. This study compared the caries experience among a weighted
      sample of Community Dental Service patients aged 4-13 years for the period
      January-December 1992 among 4138 Aboriginal children, 9674 non-Aboriginal
      Australian-born children, and 957 overseas-born children resident in Northern
      Territory, Australia. The outcomes considered included the aggregate numbers of
      decayed, missing and filled deciduous (dmft) and permanent (DMFT) teeth. Oral
      disease experience and prevalence of untreated oral disease were higher among
      Aboriginal and overseas-born children. An analysis of variance using planned
      comparisons indicated that there were significantly more decayed teeth and higher
      aggregate caries experience in the deciduous and permanent dentition of
      Aboriginal and overseas-born children than of non-Aboriginal Australian-born
      children, while overseas-born children also had more fillings and fissure
      sealants than the non-Aboriginal Australian-born children.

PMID- 9277007
TI  - High mortality despite good care-seeking behaviour: a community study of
      childhood deaths in Guinea-Bissau.
AB  - The care-seeking behaviour of mothers of 125 children deceased aged 1-30 months
      was investigated by verbal autopsy in an urban area of Guinea-Bissau. A total of
      93% of the children were seen at a health centre or hospital during the 2 weeks
      before death. In a previous survey covering the period 1987-90 we found that 78%
      of the children who died had presented for consultation (8); despite this
      increase in care seeking, infant mortality had not decreased. Comparison of
      elapsed time from disease onset to first consultation between children who died
      and matched surviving controls indicated that the interval was shorter for
      children who died than for those who survived (odds ratio (OR) = 0.7; 95%
      confidence interval (CI): 0.5-0.99). Of the 125 terminally ill children, 56 were
      hospitalized. A total of 20 children died on the way to hospital or while waiting
      in the outpatient clinic. Lack of hospital beds resulted in 15 mothers being
      refused hospitalization for their child. Of hospitalized children, 42% were
      discharged as improved or recovered during the 30 days preceding death. These
      results reveal a need for improved hospital admission criteria, improved
      recognition of the symptoms of serious illness, better discharge criteria, and
      the implementation of quality assurance systems for health services.

PMID- 9277008
TI  - An age- and sex-structured HIV epidemiological model: features and applications.
AB  - An important challenge in modelling the human immunodeficiency virus
      (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic is to use the increasing
      quantity of disease surveillance data to validate estimates and forecasts.
      Presented is a novel model for forecasting HIV incidence by age and sex and among
      sentinel groups for which data are available. This approach permits a closer
      relationship between forecasting and surveillance activities, and more accurate
      estimates validated to data. As inputs the model uses an estimate of the HIV
      prevalence, country demographic data, and a profile of the sexual risk of HIV
      infection by age, to project HIV incidence, prevalence, number of AIDS cases and
      population. The following examples of the use of the model are given: forecasting
      HIV incidence in East Africa, by age, sex, and among pregnant women; 3-5-year
      forecasts of HIV incidence; modelling mixed risk behaviour HIV epidemics in South
      east Asia; demographic indicators; and targeting a preventive vaccine by age
      group.

PMID- 9277009
TI  - Analysis of quality assurance programmes for HIV screening in blood transfusion
      centres in Delhi.
AB  - The safety of blood transfusion has attained tremendous importance because of the
      problems posed by acquired immunodeficiency syndrome (AIDS) and other transfusion
      transmissible diseases. While performing screening tests for human
      immunodeficiency virus (HIV) antibodies in donated blood is indispensable, it is
      also essential to introduce an effective quality assurance programme covering
      inspection of specimens, review of record-keeping, maintenance of equipment, and
      verification of results. We carried out an analysis of such quality assurance
      programmes during routine annual inspection of 11 blood transfusion centres in
      Delhi, India. The following parameters were studied: standardization of sample
      collection and handling; adherence to the recommended technical procedure; use of
      standard operating procedure; proper use of test reagents; laboratory record
      keeping; proper handling of HIV-positive blood units; recording and communication
      of results; observation of safety guidelines; equipment quality control; and
      training of staff. A pretested closed-type questionnaire with a weighted scoring
      system was used for evaluation. Performance for each parameter was graded as
      follows: 76-100%, excellent; 51-75%, good; 26-50%, fair; and < 25%, poor. Centres
      were categorized according to the total score obtained for all parameters.
      Overall performance > 50% was considered satisfactory. Of the 11 centres, none
      was excellent overall, five were considered satisfactory, and six were
      unsatisfactory.

PMID- 9277010
TI  - Impact of annual dosing with ivermectin on progression of onchocercal visual
      field loss.
AB  - Reported are the results of a randomized, double-masked, placebo-controlled trial
      of annual ivermectin dosing in 34 rural communities, Kaduna State, northern
      Nigeria, where guinea savanna onchocerciasis is mesoendemic. A total of 939
      individuals underwent Friedmann field analysis at the first examination and saw
      at least 19 spots in at least one eye. Of these, 636 (68%) completed a subsequent
      Friedmann field analysis 2-3 years later. The adjusted incidence rate ratio for
      the ivermectin group versus the placebo group was 0.64 (95% confidence interval
      (CI): 0.42-0.98). There was some evidence that the impact of ivermectin was
      greatest among those who had received one dose of ivermectin. The majority of the
      deteriorations occurred in eyes that gave evidence of optic atrophy at the first
      examination. An analysis restricted to individuals with optic atrophy at baseline
      indicated a reduction of 45% in the incidence of visual field deterioration in
      the ivermectin group (95% CI: 8-67%). Previous findings have shown that
      ivermectin has an impact on the incidence of optic atrophy. Our results indicate,
      for the first time, that ivermectin has a substantial impact on the progression
      of visual field loss among those with pre-existing optic atrophy.

PMID- 9277012
TI  - Control of Schistosoma haematobium morbidity on Pemba Island: validity and
      efficiency of indirect screening tests.
AB  - Four indirect screening methods for the detection of Schistosoma haematobium
      morbidity are compared (history of haematuria, visual haematuria, and
      microhaematuria at the 1+ and 2+ positivity limit by reagent strips) in terms of
      their diagnostic performance under conditions of progressive decrease in
      prevalence of infection, intensity and risk of morbidity as a result of repeated
      schistosomiasis control programmes on Pemba Island, United Republic of Tanzania.
      The results show that the sensitivity of a history of haematuria was higher (71%)
      in children but lower in adults (40%), similar to the findings for visual
      haematuria in children (60%) and adults (40%) at baseline. However, visual
      haematuria had a higher specificity, positive predictive value, and efficiency
      than a history of haematuria in both children and adults. Microhaematuria at the
      1+ positivity limit (by reagent strips) had the highest sensitivity of all the
      methods investigated, but the lowest specificity, positive predictive value, and
      efficiency. Quantitatively, the indirect methods tended to increase in
      specificity, negative predictive value, and efficiency during the course of the
      intervention programme. In contrast, positive predictive value tended to
      decrease, while the sensitivity remained fairly stable. Overall, these findings
      suggest that a history of haematuria and/or visual haematuria are appropriate
      methods for preliminary screening of communities to identify those at risk of
      morbidity. Thereafter, microhaematuria (1+ positivity limit) may be the more
      appropriate method for targeting intervention at the individual level.

PMID- 9277011
TI  - Required duration of combined annual ivermectin treatment and vector control in
      the Onchocerciasis Control Programme in west Africa.
AB  - In the extension areas of the Onchocerciasis Control Programme in West Africa,
      aerial larviciding is supplemented with annual ivermectin treatment, mainly to
      achieve better control of morbidity. The purpose of this study is to determine
      whether and to what extent the addition of annual ivermectin treatment permits
      earlier cessation of vector control than originally recommended. The
      effectiveness of combined ivermectin distribution and vector control was assessed
      using an epidemiological model. Model predictions suggest that, dependent on the
      pre-control endemicity of the area and the proportion of persons treated during
      each ivermectin round, large-scale annual treatment permits a considerable
      reduction in the duration of vector control. Taking into account uncertainty
      about the efficacy of ivermectin, our results indicate that, provided treatment
      coverage is at least 65% and there is no importation of infection from elsewhere,
      12 years of combined control will be sufficient to reduce the risk of
      recrudescence to below 1% in even the most afflicted areas.

PMID- 9277013
TI  - Current status of cutaneous leishmaniasis in Aleppo, Syrian Arab Republic.
AB  - Cutaneous leishmaniasis has been endemic in Aleppo, Syria, for generations.
      Recently there has been a clear increase in the incidence of the disease, and
      more patients have shown a lack of response to antimonials. We report the results
      of a survey, undertaken over the period 2-17 January 1995, at a general hospital
      in Aleppo, of all patients presenting with cutaneous leishmaniasis. Patients were
      grouped according to the stage of their disease, and surgical biopsies were
      carried out for histopathological investigation. Patients who were unresponsive
      to treatment and proceeded to chronicity were predominantly children aged under
      15 years with facial lesions. Histopathological examination showed that the
      inflammatory changes had reached the upper layers of the subcutaneous tissues in
      10 of the 25 chronic cases (40%) and three of the four acute cases (75%). These
      levels of the skin are not directly reached by the antimonials administered
      intralesionally. The inadequacy of the intralesional method alone and technical
      errors in administration are discussed.

PMID- 9277016
TI  - An outbreak of infectious syphilis in Bristol.

PMID- 9277015
TI  - Entamoeba taxonomy.

PMID- 9277017
TI  - Magical realism: a cultural intervention for traumatized Hispanic children.
AB  - A case study is presented of two Spanish-speaking immigrant children who were run
      over in an automobile accident and hospitalized, to describe a culturally
      congruent play-therapy technique. Drawing on the work of Pynoos and Nader, the
      author argues for an anthropological approach in play therapy to create
      hyperaroused states for the traumatized child and to use cultural super heroes
      what is termed "magical realism." Such an approach can be used with Latin
      American traumatized children as well as with children from other Third World
      countries to provide a culturally appropriate intervention to treat the
      psychological sequelae of trauma.

PMID- 9277018
TI  - "Honeymoon psychosis" in Japanese tourists to Hawaii.
AB  - Although Japanese tourists in Hawaii are infrequently treated for acute
      psychiatric emergencies, we observed several cases among Japanese honeymooners.
      To investigate this phenomenon, we retrospectively and prospectively collected
      such cases of honeymooners. Sixteen cases of acute psychiatric disturbance in
      Japanese honeymooners in Hawaii are described. This phenomenon occurs more
      frequently than in other Japanese tourists or non-Japanese honeymooners. The
      tradition of arranged marriage and other cultural factors may be associated with
      the potential for "honeymoon psychosis."

PMID- 9277014
TI  - Hypoglycaemia of the newborn: a review.
AB  - It is almost a century since hypoglycaemia (a reduction in the glucose
      concentration of circulating blood) was first described in children, and over 50
      years since the condition was first recognized in infants. Nevertheless,
      controversy still surrounds the definition, significance, and management of
      neonatal hypoglycaemia. Technological developments such as bedside glucose
      monitoring have, paradoxically, exacerbated rather than eased the situation. This
      article reviews the literature on hypoglycaemia of the newborn, and covers the
      following: historical aspects; glucose homeostasis and metabolic adaptation at
      birth; the effect of low blood glucose levels on the central nervous system; the
      definition of hypoglycaemia; screening; prevention; treatment; research needs;
      and concludes with recommendations for prevention and management.

PMID- 9277020
TI  - Ethnic diversification in clinical psychology graduate training.
AB  - Thirty-eight directors and 334 advanced graduate students from clinical
      psychology programs completed a survey on ethnic minority training offered in
      clinical doctoral programs. Comparisons were made between directors' and
      students' ratings on the following variables: students' level of interest in
      ethnic minority training, the importance of this training, and the effectiveness
      of the clinical programs' minority-related education. Minority and nonminority
      students' responses were also compared on these variables. Supplementary data
      were collected on ethnic minority education in coursework, research, and clinical
      practica. Findings indicate that students, relative to clinical directors, assign
      more importance to ethnic minority training and lower efficacy ratings to their
      programs' ethnic minority education. The results also suggest that minority
      students feel more strongly about the value of ethnic minority training than do
      their nonminority peers and the directors. The implications of these results are
      discussed, and recommendations are made to address identified problems.

PMID- 9277019
TI  - The effects of acculturative stress on incarcerated Alaska Native and non-Native
      men.
AB  - The relationship of acculturative status, acculturative stress, and interpersonal
      violence was examined in a study consisting of 73 incarcerated Alaska Native and
      non-Native men. The instruments used were the Acculturation Scale, Padilla SAFE
      Acculturative Stress Measure, Conflict Tactics Scale, Rorschach test, and the
      Perceived Stress Scale. Results found few inmates in the marginal group and no
      relationship between acculturative status and acculturative stress. Native
      inmates had significantly higher levels of acculturative stress than non-Native
      inmates, and other measures of stress did not discriminate between these two
      groups. Only non-Native inmates had higher levels of interpersonal violence
      related to acculturative stress, but their experience of acculturative stress was
      compounded by perceived, chronic, and situational stress. Apparently, non-Native
      inmates' feelings of acculturative stress are actually a sense of being
      discriminated against unrelated to their ethnicity. Bicultural inmates had
      significantly higher levels of violence than assimilated inmates did. For these
      inmates, acculturative stress is not the link between cultural conflict and
      interpersonal violence, but attempting to be a part of both cultures may be. The
      problem for these inmates seems to be in adapting to their cultural orientation,
      not in the orientation itself. While in prison, many native men seem to cope by
      renewing their cultural and spiritual practices, which may be providing them with
      a cultural identity they did not possess before incarceration. Acculturative
      status may need to be viewed as a continuum and a conscious choice. Implications
      for treatment and further research are discussed.

PMID- 9277021
TI  - Culturally sensitive integration of supportive and cognitive behavioral therapy
      in the treatment of a bicultural dysthymic patient.
AB  - A single case study is presented of the successful integration of culturally
      sensitive supportive and cognitive behavioral therapy to meet the needs of a
      bicultural man (Mexican/Palestinian) with dysthymia. The patient, a 3rd-year law
      student, was chronically making self-depreciating negative verbalizations that
      disrupted his daily functioning. The outcome revealed that the therapeutic
      alliance was improved by having a therapist of color who was sensitive to
      cultural issues and acculturation. Supportive therapy, coupled with cognitive
      behavioral interventions, succeeded in extinguishing the patient's negative
      verbalizations, and in normalizing his daily functioning. Treatment effects were
      maintained at follow-up.

PMID- 9277022
TI  - Survey of the cross-cultural content of U.S. psychiatry residency training
      programs.
AB  - To establish the extent of cross-cultural content contained in the 224
      psychiatric residency training programs, the Directors of Residency Training were
      surveyed by mail. Thirty-seven percent (N = 83) of Directors responded; 92% (N =
      76) had cross-cultural content, 99% (N = 82) had opportunities to work with
      minority patients, and 77% (N = 64) had supervision by some minority faculty.
      Responding programs reported a need for teaching videotapes (85%, N = 71), cross
      cultural references (78%, N = 65), academic psychiatrists familiar with different
      cultural groups (76%, N = 63), and cross-cultural supervision (75%, N = 62).

PMID- 9277023
TI  - Effects of a mass media behavioral treatment for chronic headache: a pilot study.
AB  - This article presents the results of a pilot study evaluating the efficacy of a
      mass media self-help behavioral treatment program for chronic headache. The
      program consisted of a self-help textbook, an exercise book, 10 television
      programs, 11 radio programs, and 3 audiocassettes with relaxation training.
      Approximately 15,000 headache sufferers purchased the book and relaxation tapes.
      A random sample of 271 respondents participated in the effect study; the
      pretraining and posttraining data of 164 subjects were available for analysis.
      Multivariate testing of the pretraining and posttraining results showed highly
      significant reductions in headache activity and medication intake at 4-month
      follow-up. A reduction of 50% or more in headache parameters and medication
      intake was achieved by 40% to 60% of the patients. Work absenteeism was
      significantly reduced. The differences between the diagnostic groups were not
      significant. Mass media behavioral treatment seems to be a viable treatment
      alternative for chronic headache and highly promising in terms of gain in quality
      of life, decrease in economic loss, and cost-effectiveness in health care.

PMID- 9277025
TI  - The comparison of individuals with tension-type headache and headache-free
      controls on frontal EMG levels: a meta-analysis.
AB  - For many years, the dominant theory of tension-type headache has been that
      individuals who suffer from these headaches have elevations in electromyographic
      (EMG) activity at rest or during stressful life experiences. This theory has come
      under increasing attack in recent years. Although the research that is relevant
      to the controversy has been reviewed previously using box score and voting
      methods, no one has analyzed the relevant data using a statistical approach. This
      study used meta-analysis to summarize the studies that have directly compared
      individuals with tension-type headache to headache-free control subjects on
      measures of frontal EMG at baseline and during rest. Twenty-three studies were
      included in the analysis. The overall effect size was .395; however, there was
      heterogeneity of effect size. Several potential moderator variables were
      investigated. Perhaps the most interesting moderator variable was whether the
      studies clearly stated that subjects were headache-free during assessment. This
      group of studies produced a nonsignificant effect size that had homogeneity of
      effects. Several interpretations of the results are presented.

PMID- 9277024
TI  - Sumatriptan in the acute treatment of migraine without aura: efficacy of 50-mg
      dose.
AB  - We conducted an open study on the efficacy of 50 mg of sumatriptan as an acute
      treatment for migraine without aura. We recruited 200 consecutive patients, with
      an established history of migraine without aura, presenting at a headache center.
      The patients were instructed to take half a 100-mg sumatriptan tablet for their
      next migraine attack, and to record details of their headache in a diary. The
      primary outcome of the study was headache relief from one migraine attack.
      Attacks were moderately intense (46%), moderate to severe (7%), or severe (47%).
      Total or partial benefit at 2 hours from the 50-mg dose was reported by 140 of
      200 patients (70%). Thirty-six patients received no benefit from half a tablet,
      and 24 did not take sumatriptan, preferring their habitual medication. Side
      effects were few, mild, and short lasting. We conclude that the 50-mg oral dose
      is generally effective for migraine without aura attacks of both moderate and
      severe intensity and recommend this dose for all such patients. If, however,
      sumatriptan is ineffective at that dose it can be increased to a maximum of 100
      mg.

PMID- 9277026
TI  - Protriptyline, chronic tension-type headaches, and weight loss in women.
AB  - Twenty-five women with chronic tension-type headaches were treated with
      protriptyline for 3 months, with attention paid to days of monthly headaches
      before and while taking the medication, as well as change in weight and side
      effects. One patient stopped the medication because of side effects and 2 did not
      return for follow-up, yielding 22 patients. The typical dose of protriptyline was
      20 mg every morning. Eighty-six percent of patients had fewer headaches each
      month, with the mean dropping from 28.2 to 11.7 days. Seventy-three percent had a
      50% or greater reduction in the number of headaches per month. The average weight
      change was a loss of slightly over 3 pounds during the study period. The
      advantages and disadvantages of protriptyline in the treatment of chronic tension
      type headaches are discussed, as are mechanisms of action.

PMID- 9277027
TI  - Methylergonovine maleate as a cluster headache prophylactic: a study and review.
AB  - Methylergonovine maleate (Methergine), an ergot derivative with vasoconstrictive
      properties, has been cited as an effective treatment for vascular headaches. Few
      studies are available to support its use in headache management. An uncontrolled
      pilot study of 20 episodic cluster headache patients confirmed its effectiveness
      and tolerability as an adjunct cluster headache prophylactic. Decreased headache
      frequency was reported by 19 of 20 patients (95%), and 15 of 20 patients (75%)
      reported decreased intensity of headaches within 1 week of initiating therapy. A
      review of methylergonovine's pharmacokinetic, molecular, and tolerability profile
      clarifies its mechanisms and clinical role in headache management.

PMID- 9277029
TI  - Pattern-reversal visual evoked potentials in migraineurs with or without visual
      aura.
AB  - To determine the possible electrophysiologic changes in migraineurs with or
      without visual aura, we investigated pattern-reversal visual evoked potentials in
      39 patients. We compared the mean P100 latency and amplitude of 16 patients with
      aura, 23 patients without aura, and 17 age- and sex-matched normal subjects.
      There were no significant differences between groups. There was no correlation
      between age and the parameters in any group. However, in 7 of 23 patients without
      aura, the P100 latency was longer than the mean control value +2 SD. The mean
      disease duration in this subgroup was significantly longer than the means of the
      remaining 16 patients without aura or the patients with aura (P < 0.05 for each).
      This suggests the possibility that P100 latency prolongation is a consequence,
      but not an entity caused by the pathogenetic mechanism of the disease from the
      beginning.

PMID- 9277028
TI  - Recurrent 'migrainelike' episodes in patients with HIV disease.
AB  - Recurrent transient neurological deficits have been described in human
      immunodeficiency virus (HIV)-infected subjects, but their frequency,
      pathogenesis, and outcome are still unsettled. We describe 10 HIV-infected
      patients with transient neurological deficits (0.8% of all patients followed in
      our department during the last decade). All patients were in the advanced stage
      of immunological disease. None of the clinical or special investigations
      performed outside of the attacks indicated an underlying structural lesion of the
      central nervous system. In 80% of these patients, anticardiolipin antibodies were
      present. The final outcome was unrelated to these transient neurological deficits
      which, per se, had a benign course. We discuss the possible etiopathogenetic
      mechanisms of such episodes and suggest that they may be "migrainelike" events,
      possibly related to transient functional circulatory abnormalities secondary to
      an immunological antiphospholipid antibody-dependent mechanism.

PMID- 9277030
TI  - Repeated doses of combined oral lysine acetylsalicylate and metoclopramide in the
      acute treatment of migraine.
AB  - The combination of lysine acetylsalicylate and metoclopramide is effective in the
      treatment of migraine attacks. It was unknown whether repeated doses could
      improve efficacy. The aim of this open trial was to evaluate the effects of a
      second, and eventually a third dose of lysine acetylsalicylate and metoclopramide
      when a first dose of the treatment was ineffective. Patients were asked to take a
      second dose 2 hours after a first dose when they thought that the first dose was
      ineffective. They were allowed to take a third dose or their rescue medication 2
      hours after the second dose when they judged that the treatment remained
      ineffective. Two hundred ninety-two patients were included in the study; 262 of
      the 292 patients treated 517 attacks. Headache relief (reduction in headache
      severity from grade 3 or 2 to grade 1 or 0) was observed in 54.8% of attacks
      after one dose, in 48.1% of attacks after a second dose, and in 40.3% of attacks
      after a third dose. Complete headache relief without recurrence and without use
      of a rescue medication was reported in 37% of the total attacks. The patients
      judged their treatment as good or excellent in 78% of attacks treated with one
      dose, in 41% of those treated with two doses, and in 19% of those treated with
      three doses. Tolerance, as judged by the patients, was considered good in 92% of
      treated attacks. Minor side effects occurred in 6% of attacks after a first dose,
      in 4.5% of attacks after a second dose, in 1.5% of attacks after a third dose, in
      2% after unspecified delay, and in 14% overall. In conclusion, the efficacy of
      lysine acetylsalicylate and metoclopramide in the treatment of migraine attacks
      can be improved by repeated doses. It is well tolerated.

PMID- 9277031
TI  - Migrainelike headache in a patient with a hemorrhagic pituitary macroadenoma.
AB  - A 23-year-old woman presented with a 4-day history of a severe migrainelike
      headache with a normal neurological examination. The headache resolved after a
      ketorolac injection, but recurred a few hours later. An MRI scan of the brain
      showed a hemorrhagic pituitary macroadenoma for which she underwent
      transsphenoidal removal of the tumor 1 month later. Although uncommon, pituitary
      hemorrhage with and without apoplexy should be considered in the differential
      diagnosis of acute headache. Pituitary hemorrhage can be routinely identified on
      an MRI scan even without pituitary views. However, the pathology can be
      overlooked and underimaged on a CT scan for acute headache using 10-mm and even 5
      mm slices.

PMID- 9277032
TI  - Transverse sinus thrombosis: an unusual cause of headache.
AB  - A 24-year-old woman presented with headache of 6 days' duration, described as
      throbbing pain in the right periorbital region radiating to her right ear and
      neck. The pain was unresponsive to oral analgesics. She had no speech or hearing
      difficulties, no previous history of migraines, and no family history of
      neurologic disease. Her medications included oral contraceptives for 8 months'
      duration. This report describes the salient features of dural sinus thrombosis
      and recent advances in diagnostic and therapeutic procedures. The relationship
      between oral contraceptives and protein S levels is also discussed. Cerebral
      dural sinus thrombosis should be considered in the differential of new onset of
      headaches, seizures, or focal neurological deficits.

PMID- 9277033
TI  - Headache caused by a sphenoid mucocele but presenting as an ergotamine-induced
      headache.
AB  - In a 65-year-old woman, symptomatic headache caused by a mucocele of the sphenoid
      sinus led to ergotamine abuse and subsequent ergotamine-induced headache. Since
      there were no neurological symptoms initially and the patient previously suffered
      from migraine, the mucocele was not recognized. Only after unsuccessful drug
      withdrawal therapy and an MRI, was the correct diagnosis made. Surgical removal
      of the mucocele led to complete relief of headache within 3 weeks. We conclude
      that ergotamine-induced headache can develop on the basis of symptomatic
      headache. In spite of the effectiveness of ergotamine tartrate, an MRI should be
      performed if focal neurological symptoms occur.

PMID- 9277034
TI  - Migraine-related stroke versus migraine-induced stroke.

PMID- 9277035
TI  - An outbreak of post-streptococcal reactive arthritis.
AB  - We describe an outbreak of an illness with fever, mono-, pauci- or polyarticular
      arthritis, and high antideoxyribonuclease B (ADNB) titres in 11 patients. Two
      patients had concomitant non-purulent conjunctivitis and one had endogenous
      endophthalmitis. There was no clinical or echocardiographic (6 patients) evidence
      of carditis. Blood culture grew Group A beta haemolytic streptococci in one
      patient. A simultaneous synovial fluid culture in this patient and similar
      cultures in four more patients yielded no microorganism. Most patients recovered
      completely, but one developed rheumatoid factor negative spondyloarthropathy.
      Monoarticular arthritis in several patients, the absence of carditis, and the
      presence of high ADNB titres without high anti-streptolysin O titres indicate
      that this was not acute rheumatic fever but post-streptococcal reactive arthritis
      (PSRA).

PMID- 9277036
TI  - Isolation of Vibrio cholerae 0139 phages to develop a phage typing scheme.
AB  - Five V. cholerae 0139 phages isolated from different parts of India have been
      used for phage typing study. A strain isolated from Nagpur city (NPR-4) was used
      as the host for phage propagation. All but one of the 260 strains of V. cholerae
      0139 were found to be typeable and could be clustered into 8 distinct phage types
      as revealed by lytic patterns. Phage type 1 was the predominant type (61.15%)
      followed by type 2 (18.46%). The strains isolated from Madras exhibited 7 out of
      8 phage types. These newly isolated phages could be adopted for phage typing of
      V. cholerae 0139 strains as an epidemiological tool.

PMID- 9277037
TI  - In vitro adhesiveness of Bacteroides fragilis group in relation to encapsulation.
AB  - The adhesive properties of the B. fragilis group to various erythrocytes were
      studied by haemagglutination technique and compared to encapsulation. Of the 61
      strains of Bacteroides groups tested, only 40 strains of B. fragilis exhibited
      haemagglutination. Treatment of the organisms with carbohydrates and trypsin had
      no effect on haemagglutination, but boiling for one hour completely destroyed
      this property. Haemagglutinating activity of B. fragilis was found to be the
      highest with chick and tanned sheep erythrocytes. The presence of capsule was
      observed in 46 strains of B. fragilis group. Of the 40 strains of B. fragilis
      which exhibited agglutination, capsule was found only in 37. The findings of the
      study suggest a polysaccharide nature for the adhesin. The different patterns of
      haemagglutination, suggest the involvement of more than one adhesin. Capsule in
      capsulated strains and fimbriae in non-capsulated strains might be mediating the
      property of haemagglutination.

PMID- 9277038
TI  - Anaerobic flora in endodontic infections.
AB  - Microbiological and clinical data from 56 patients with endodontic infections
      were evaluated. Samples were collected using autoclaved paper points. Specimens
      were processed for isolation of aerobic and anaerobic bacteria. Antimicrobial
      sensitivity and resistance profiles of the recovered isolates was also performed.
      Forty nine positive cultures (87.5%) were obtained from the 56 consecutive
      necrotic root canal systems which were sampled. A total of 69 aerobic bacteria
      and 21 anaerobic bacteria were recovered. Aerobic bacteria were isolated from 35
      patients (72%), anaerobic bacteria from 3 (6%) and mixed aerobic and anaerobic
      bacteria from 11 patients (22%). The most common aerobic isolate was Klebsiella
      pneumoniae. The predominant anaerobic isolate was Bacteroides species. One
      isolate was recovered from 25 patients (51%) whereas in the remaining 24 patients
      (49%) more than 1 isolate were recovered. These data illustrate the polymicrobial
      nature of endodontic infections in half the patients studied and the role of
      anaerobic bacteria in a quarter of them.

PMID- 9277039
TI  - The effect of in vitro bacterial association on virulence of Entamoeba
      histolytica.
AB  - When trophozoites of axenic E. histolytica strains NIH : 200 were associated in
      vitro with Escherichia coli K12 for three hours at 37 degrees C, the virulence
      was enhanced as shown by increased cytopathogenicity to baby hamster kidney (BHK)
      cell monolayer. Further, the trophozoites were observed to adhere to the
      polystyrene surface, a hitherto unreported phenomenon. The co-association of E.
      histolytica trophozoites with Bacteroides fragilis and Clostridium perfringens
      for three hours duration at 37 degrees C neither led to increase in cytotoxicity
      potential nor to adherence phenomenon; in contrast significant inhibition of
      cytotoxicity was observed. We have thus shown that while co-association of E.
      histolytica (NIH : 200) with E. coli K12 leads to enhanced amoebic virulence,
      that with anaerobic bacteric leads to its inhibition.

PMID- 9277040
TI  - HLA antigen pattern of Kashmiri patients with rheumatic heart disease.
AB  - The distribution of HLA class-I (A, B and C), and class II (DR and DQ) antigens
      was studied in 50 randomly selected Kashmiri Muslim patients with established
      rheumatic heart disease and compared with that of 50 controls of similar
      ethnicity. A significant increase in the frequency of HLA-DR4 (P < 0.005, RR
      3.27) and a significant decrease in the frequency of HLA-B5 (P < 0.001, RR 0.19)
      were found in the patient group. Though HLA-DQ3 showed a significant increase (P
      < 0.005, RR 2.52) and HLA-DR7 a significant decrease (P < 0.05, RR 0.42) in the
      patient group, the corrected P value was not significant. The findings suggest
      that susceptibility to RHD in the studied population is HLA-related, with HLA-DR4
      influencing its occurrence and HLA-B5 conferring protection against the same.

PMID- 9277041
TI  - Detection of beta-thalassaemia mutation insertion ATCT at codon 47/48 by ARMS
      technique for screening & prenatal diagnosis.
AB  - We report the diagnosis of the newly identified mutation codon 47/48 insertion
      ATCT using allele specific primers by the PCR-based amplification refractory
      mutation system (ARMS). Using this method prenatal diagnosis was provided to five
      couples at risk for this mutation. The assay provides an easy, non-isotopic
      method for identifying this mutation in cases which remain uncharacterized after
      screening for the 5 'common' and 12 'rare' Indian mutations. It will be useful
      for screening and prenatal diagnosis in at risk couples and help in the
      thalassaemia control programme in India.

PMID- 9277042
TI  - Evaluation of some risk factors for ischaemic heart disease under a matched pairs
      case-control design.
AB  - A pair-wise matched case-control study was carried out in 200 male patients of
      ischaemic heart disease (IHD). The cases were matched with an equal number of
      controls in respect of the variables viz., age and socio-economic status. The
      objective was to quantify the risk of developing IHD for some of the leading risk
      factors under the univariate and multivariate situations. The analysis revealed
      that of the factors (smoking, overweight, hypertension, diabetes, serum
      cholesterol and family history) considered, the smoking habit of the individual,
      presence of family history of the disease and overweight were the significant
      risk factors responsible for the development of the disease. The estimated odds
      ratios were found to be 3.29, 2.60 and 2.00 respectively.

PMID- 9277043
TI  - Immune mechanism of aplastic anemia.
AB  - Immune-mediated suppression of hematopoiesis has been considered the most
      important mechanism in the development of idiopathic aplastic anemia (AA), mainly
      based on high rates of response to immunosuppressive therapy in patients with AA.
      However, the lack of an experimental animal model and the heterogeneity of the
      disease has hindered elucidation of immune mechanisms underlying AA. Recent
      studies on a subset of AA patients characterized by repetitive response to
      cyclosporine (CyA) therapy revealed a strong association of HLA-DRB1*1501 with
      susceptibility to such immune-mediated AA. Other studies of the T-cell clonotype
      in the bone marrow (BM) of the patients using the polymerase chain reaction (PCR)
      single strand conformation polymorphism analysis and sequencing of T-cell
      receptor V beta cDNA showed dominant proliferation of a limited number of T
      cells, indicating the presence of certain antigenic stimuli in the BM. More
      recently, we isolated a CD4+ T-cell clone that proliferated most dominantly among
      V beta 21+ T-cells in the BM of a CyA-dependent AA patient and was capable of
      killing autologous hematopoietic cells. Lysis of allogeneic hematopoietic cells
      by this T-cell clone required the presence of HLA-DR4 on the target cells.
      Further studies on such T-cell clones will help identify key molecules on
      hematopoietic cells that induce the development of AA.

PMID- 9277044
TI  - Differential diagnosis of hemophagocytic syndrome: underlying disorders and
      selection of the most effective treatment.
AB  - Hemophagocytic syndrome consists of primary and secondary HLH. Efficacy of
      therapeutic measures and prognosis depend on degree of hypercytokinemia
      associated organ failure at disease onset and underlying disorders. The
      underlying diseases related to hemophagocytosis and informative markers useful
      for differential diagnoses to select the most effective treatment are discussed.
      Differential diagnosis is difficult between confirmed FEL and familiality-unknown
      infantile VAHS (or sporadic FEL cases) in primary HLH and also among IAHS, benign
      EB-VAHS and EBV-related LAHS in secondary HLH. For primary HLH, assay of NK
      activity and for secondary HLH, studies on the serum cytokine pattern, EBV
      genomes and clonality determination might prove useful.

PMID- 9277045
TI  - Identification of the truncated Duffy mRNAs in erythroid cells.
AB  - Chaudhruri et al. reported the Duffy glycoprotein cDNA (Fy71-81) (Proc Natl Acad
      Sci USA 1990; 90; 10793), and we cloned a novel Duffy cDNA named Fy0.1 (Blood
      1996; 87: 378). Reverse transcription-polymerase chain reaction analysis revealed
      the presence of the four truncated mRNAs associated with both transcripts. The
      truncated Duffy mRNAs is predominantly present in reticulocytes but is not
      detected in the erythroblasts. The sequencing data indicated that the truncated
      Duffy mRNAs were processed by splicing. Further study is needed to clarify the
      biological role of the truncated Duffy mRNA in reticulocytes.

PMID- 9277046
TI  - Serum erythropoietin during normal pregnancy: relationship to hemoglobin and iron
      status markers and impact of iron supplementation in a longitudinal, placebo
      controlled study on 118 women.
AB  - Serum erythropoietin (EPO) and its relationship to hemoglobin (Hb), iron status
      markers and iron supplementation during normal pregnancy was assessed in a
      longitudinal, placebo-controlled study on 118 women, 61 took daily tablets
      containing 66 mg ferrous iron from the second trimester until delivery and 57
      took placebo. Blood samples were obtained at 4-week intervals until delivery as
      well as post-partum. In the placebo-treated women, median serum EPO rose from
      22.5 U/l at inclusion to 35.0 U/l at delivery (P = 0.0001). In the iron-treated
      women, median serum EPO rose from 23.9 to 29.9 U/l (P = 0.0001). Serum EPO showed
      a steeper increase in the placebo-treated women than in the iron-treated women (P
      < 0.05). After delivery, serum EPO became normal in both groups (P = 0.0001).
      Median Hb was lower in placebo-treated (iron depleted) than in iron-treated (iron
      repleted) women (P < 0.05). In the placebo-treated women there was a negative
      correlation and in the iron-treated women a positive correlation between serum
      EPO and Hb. In the placebo-treated women, inverse correlations existed between
      serum EPO and serum transferrin saturation and serum ferritin, reflecting the
      consequences of iron deficiency, whereas the iron-treated women displayed no
      correlation. A physiological, nonhypoxia-induced increase in EPO production
      accounts for the basic expansion of the red cell mass during pregnancy. In
      placebo-treated women, iron deficient erythropoiesis constitutes an additional
      hypoxic stimulus, which induces a further increase in serum EPO.

PMID- 9277047
TI  - G-CSF-induced mobilization of peripheral blood stem cells for allografting:
      comparative study of daily single versus divided dose of G-CSF.
AB  - We conducted a comparative study on a daily single versus a divided dose of G-CSF
      for G-CSF-induced mobilization of peripheral blood stem cells (PBSC) in eleven
      HLA-identical sibling donors of allogeneic PBSC transplantation (PBSCT). Six
      donors received double subcutaneous injections of G-CSF at a dose of 5
      micrograms/kg x 2/day for 5 days (Group A), while the remaining five received
      single subcutaneous injection at a dose of 10 micrograms/kg/day for 5 days (Group
      B). The numbers of circulating CD34+ cells, myeloid progenitors (CFU-GM) and
      erythroid progenitors (BFU-E) reached peak values at day 5 of G-CSF
      administration in both groups. The mean number of CD34+ cells harvested per
      apheresis was 4.4 x 10(6)/kg (cells/body weight of each donor, range: 0.8-7.9 x
      10(6)/kg) in Group A and 5.1 x 10(6)/kg (range: 3.0-9.0 x 10(6)/kg) in Group B.
      There were no significant differences between these two groups in total numbers
      of CFU-GM, BFU-E, or T-lymphocytes harvested. Adverse effects including mild to
      moderate bone pain and thrombocytopenia were transient and well tolerated. No
      difference was observed in the incidence of adverse effects between the two
      groups. These observations suggest that there is no difference in G-CSF-induced
      mobilization of PBSC between daily single and divided dose of G-CSF to collect a
      sufficient number of PBSC for engraftment after allo-PBSCT.

PMID- 9277048
TI  - Effects of colony-stimulating factors (CSFs) on neutrophil apoptosis: possible
      roles at inflammation site.
AB  - We found that granulocyte-macrophage colony-stimulating factor (GM-CSF) and
      granulocyte colony-stimulating factor (G-CSF) had different effects on the
      apoptosis of human mature neutrophils induced by anti-Fas antibody. GM-CSF
      suppressed this process and neutrophils retained their functions of superoxide
      production and enzyme release against invasion of microorganisms. In contrast, G
      CSF had a weaker effect on the anti-Fas antibody-induced neutrophil apoptosis
      than GM-CSF, with neutrophil function suppressed in proportion to the apoptosis.
      GM-CSF produced by satellite cells at the inflammatory site may inhibit apoptosis
      and the neutrophils may maintain their primed functions to kill the invading
      microorganisms. G-CSF produced by fibroblasts or endothelial cells may work in
      another fashion by increasing the number of neutrophils more effectively than GM
      CSF. GM-CSF and G-CSF may exert different effects on neutrophils at the
      inflammatory sites in the human body.

PMID- 9277049
TI  - Subcellular localization of the MEN, MLL/MEN and truncated MLL proteins expressed
      in leukemic cells carrying the t(11;19)(q23;p13.1) translocation.
AB  - The t(11;19)(q23;p13.1) translocation is exclusively associated with myeloid
      leukemias. Previously, we cloned several species of MLL/MEN chimeric cDNAs in a
      patient with myeloid leukemia carrying the t(11;19)(q23;p13.1) translocation. The
      MEN sequence directly followed the 5' region of MLL cDNA in some species and
      otherwise there presented an inserted sequence of 120 bp between the MLL and MEN
      sequences in others. Because the insertion sequence contained an in-frame
      termination codon, they coded only for the NH2-terminal part of MLL (truncated
      MLL). We also cloned the normal MEN cDNA in full-length with a cDNA library
      derived from K562 cells. We expressed the normal MEN, MLL/MEN chimeric and
      truncated MLL proteins in COS7 cells with the corresponding cDNAs and detected
      them with antibodies raised against the MEN and MLL peptides. Immunostaining and
      subcellular fractionation showed nuclear localization of all these proteins.
      These findings suggested that MLL/MEN chimeric cDNAs were actually translated
      into both MLL/MEN fusion and truncated MLL proteins and that they were localized
      in the nucleus of leukemic cells. Recently, Conaway et al. reported that MEN is
      an RNA polymerase II elongation factor. The leukemogenesis by the
      t(11;19)(q23;p13.1) translocation may have resulted from the alteration of
      transcription regulation induced by the MLL/MEN fusion protein and/or the
      truncated MLL protein.

PMID- 9277050
TI  - Elevated serum levels of eosinophil major basic protein in patients with
      myeloproliferative disorders without eosinophilia.
AB  - The 12- to 14-kDa eosinophil major basic protein (MBP) is primarily translated as
      25-kDa pro-MBP. HL-60, a promyelocytic leukemia cell line, produces pro-MBP but
      not MBP, suggesting production of pro-MBP by immature granulocytes. We measured
      the serum levels of total MBP, using an ELISA that detects both pro-MBP and MBP,
      in 25 patients with leukemia (six acute myelogenous leukemia (AML), seven acute
      lymphoblastic leukemia (ALL), eight chronic myelogenous leukemia (CML), four
      chronic lymphocytic leukemia (CLL)) and five recipients of allogeneic bone marrow
      transplants (BMT). None of these patients except one AML (M4Eo) showed
      eosinophilia. Serum levels of total MBP were elevated in all the patients with
      CML and AML, but not in any of those with ALL or CLL. In all four recipients of
      BMT who obtained engraftments, serum levels of total MBP started to increase 12
      14 days after BMT and reached the highest levels (4-10 times the basal levels) at
      days 19-32. In a recipient of BMT who did not obtain an engraftment, serum levels
      of total MBP were not increased. These findings suggested that pro-MBP could be
      used as a marker for proliferation of immature granulocytes with normal or
      malignant nature.

PMID- 9277051
TI  - Prediction of growth sensitivity of acute promyelocytic leukemia cells to
      granulocyte colony-stimulating factor using 7AAD/PY during administration of all
      trans retinoic acid.
AB  - We discussed utility of cell cycle and phenotypic analysis of acute promyelocytic
      leukemia (APL) cells using 7AAD/PY for the prediction of efficacy and risks of
      all-trans retinoic acid (ATRA) and granulocyte colony-stimulating factor (G-CSF)
      administration to patients with APL. Serial changes in phenotype and cell
      kinetics of APL cells from two patients were analyzed during ATRA administration.
      CD15 and CD11b were expressed on the APL cells in vivo as neutrophil maturation
      markers, while growth activity of the cells was decreased during ATRA
      administration. Using 7AAD/PY, changes in phenotype and cell kinetics were
      clearly detected after 2 days of cultivation with ATRA and/or G-CSF. In one
      patient, APL cells harvested from marrow during the first 3 weeks of ATRA
      administration showed distinct growth sensitivity to G-CSF ex vivo, and the cells
      harvested after a 4-week exposure to ATRA appeared to have lost this sensitivity.
      In this patient, G-CSF could be safely administered after 4 weeks of ATRA
      therapy. 7AAD/PY analysis is useful for predicting growth sensitivity of APL
      cells to G-CSF during ATRA administration.

PMID- 9277052
TI  - TEL/AML1 fusion gene resulting from a cryptic t(12;21) is uncommon in adult
      patients with B-cell lineage ALL and CML lymphoblastic transformation.
AB  - TEL is a new member of the ETS-like family on chromosome 12 and forms fusion
      genes with several partners in leukemia. Among these fusion genes, the TEL/AML1
      translocation resulting from t(12;21) is found in approximately one quarter of
      the childhood B-cell lineage acute lymphoblastic leukemia (ALL) cases and its
      prognosis is excellent. We examined 42 adult patients with B-cell lineage ALL and
      13 adult patients with lymphoblastic transformation of chronic myeloid leukemia
      (CML) to detect TEL/AML1 fusion genes using the reverse transcriptase-polymerase
      chain reaction (RT-PCR) and Southern blotting, but no translocation was detected.
      These findings indicate that absence of the TEL/AML1 fusion transcript partly
      correlates with the poorer outcome of adult B-cell lineage ALL as compared with
      childhood ALL and the TEL/AML1 fusion transcript is specific for pediatric B-cell
      lineage ALL.

PMID- 9277053
TI  - Hyperdiploid myeloma cell as an indicator of poor prognosis and drug
      refractoriness.
AB  - Although almost 40% of patients with multiple myeloma respond to initial
      chemotherapy, myeloma with no response to initial chemotherapy remains a serious
      problem. To understand the characteristics of drug-refractoriness of myeloma,
      fresh tumor cells from 13 untreated myeloma patients were fixed and stained with
      anti-human immunoglobulins and propidium iodide for subsequent flow cytometric
      analysis of DNA content. More than 10% of myeloma cells were hyperdiploid in
      eight cases (hyperdiploid + cases) while less than 10% of myeloma cells were
      hyperdiploid in five cases (hyperdiploid - cases). The proportion of hyperdiploid
      cells among all myeloma cells was highly correlated with incidence of myeloma
      cells with morphologically abnormal nuclei such as those with multiple-nuclei or
      convoluted nuclei (P = 0.001). Among the eight hyperdiploid + cases, two (2/8)
      showed good response to subsequent chemotherapy while four of five hyperdiploid -
      cases (4/5) responded well. Cases with poor response had more hyperdiploid
      myeloma cells (average 25.7% of all myeloma cells) than sensitive cases (average
      6.8%), suggesting a contribution of hyperdiploid myeloma cells to primary drug
      resistance (P = 0.065). The 3 year survival rate of hyperdiploid+cases was 0%
      while that of the control group was 41.9%. These results suggest that myeloma
      cells with abnormal nuclear morphology may show hyperdiploidy and poor response
      to chemotherapy.

PMID- 9277054
TI  - Hepatosplenic T-cell lymphoma: prolymphocytic transformation 18 months after
      splenectomy.
AB  - We report a young woman with pancytopenia and huge splenomegaly who was also
      found to have peripheral T-cell lymphoma with massive infiltration of T-cell
      evident in the liver and spleen. A liver biopsy showed predominant sinusoidal
      infiltration of pan-T cell antibody-stained T-lymphoid cells. Histologic
      examination of the spleen revealed numerous tumor cells predominantly infiltrated
      in the cords and sinuses of the red pulp, which were identical to those described
      in the liver. Several clusters of small round abnormal cells were observed in
      marrow cytology. Although the patient felt well during 18 months after the
      splenectomy was done, the patient eventually manifested a huge hepatomegaly,
      showed increasing white blood cell count to 42 x 10(9)/l, and numerous
      prolymphocytes (66.9%) in the bone marrow. This change represented a
      prolymphocytic transformation of the patient's original hepatosplenic T-cell
      lymphoma.

PMID- 9277056
TI  - Unrelated bone marrow transplantation from the National Marrow Donor Program.
AB  - Between November 1992 and December 1996, we carried out bone marrow
      transplantation through the National Marrow Donor Program (NMDP) for 11 patients
      who lacked an appropriate donor among their family members and the Japan Marrow
      Donor Program (JMDP). They accounted for 11% of 101 patients who had registrated
      to the NMDP Transplant Center Office in Japan. The median time required from the
      initiation of preliminary search to transplant for these 11 patients was 198
      days. The 11 donors included four Caucasians, one Native American and the others
      were Asian/Pacific islanders. A median of 17 h was required to transport bone
      marrow from harvest institutes to our hospital and their viability determined in
      our laboratory had a median of 96%. Engraftment was observed in all recipients
      and the incidence of grade III-IV acute graft-versus host disease was 27%. Of
      four patients three (75%) with chronic myelogenous leukemia in chronic phase
      (standard-risk) and two (29%) of seven patients in progressive state of the
      disease (high-risk), are alive at present. Cooperation between the JMDP and the
      NMDP, which began in April 1997, could shorten the time for donor search and
      allow transplantation to more patients with more appropriate timing.

PMID- 9277055
TI  - An HTLV-I carrier with Graves' disease followed by uveitis: isolation of HTLV-I
      from thyroid tissue.
AB  - We report a long-term (14-year) follow-up of a human T-lymphotropic virus type I
      (HTLV-I)-infected male who was successively afflicted with Graves' disease
      followed by uveitis. HTLV-I proviral DNA was detected by polymerase chain
      reaction in the thyroid tissue and HTLV-I was isolated from thyroid tissue by
      coculture with peripheral blood lymphocytes from an HTLV-I-uninfected healthy
      female. This case study supports a close relationship between Graves' disease and
      uveitis in an HTLV-I carrier.

PMID- 9277057
TI  - No CD117 expression on B progenitors in the regenerating bone marrow.

PMID- 9277058
TI  - Age-related changes of platelet arachidonic acid metabolism in normal subjects.
AB  - Platelet activation and thrombosis play a crucial role in cardiovascular
      diseases. It has been suggested that enhanced platelet function in vivo are
      present in the elderly and that they are associated with the development of these
      diseases [1-3]. In the present study, we addressed the question of whether
      platelet arachidonate metabolism was altered with aging.

PMID- 9277059
TI  - Epidurals, electronic fetal monitoring, and "Dolly". The role of technology in
      the care of women.

PMID- 9277060
TI  - Evaluation of a reduced-frequency prenatal visit schedule for low-risk women at a
      free-standing birthing center.
AB  - OBJECTIVE: to evaluate the effectiveness of a reduced-frequency prenatal visit
      schedule by comparing perinatal outcomes, anxiety and maternal satisfaction with
      prenatal care. METHODS: pregnancy outcomes of infant and maternal morbidity and
      mortality, anxiety and satisfaction for 81 women receiving prenatal care at a
      free-standing birthing center according to either an alternative prenatal care
      visit schedule (APCVS) (n = 43) or the traditional prenatal care visit schedule
      (TPCVS) (n = 38) were examined in this prospective randomized study. Upon entry
      into prenatal care, all women were of low obstetrical risk status. RESULTS: major
      findings revealed no significant differences in selected perinatal outcomes
      between the two study groups. Women in the APCVS group reported significantly
      higher levels of satisfaction than women in the TPCVS group on both the
      satisfaction with provider subscale (F = 5.74, P = .02) and the satisfaction with
      the prenatal care system subscale (F = 2.01, P = .04). There were no
      statistically significant differences found in anxiety scores between women in
      the two study groups. CONCLUSIONS: low-risk women who followed the reduced
      frequency visit schedule experienced no difference in perinatal outcomes or
      anxiety. Women in the reduced-frequency (APCVS) group reported an increased level
      of satisfaction with both provider and the prenatal care system.

PMID- 9277061
TI  - Vaginal birth after cesarean in a hospital-based birth center staffed by
      certified nurse-midwives.
AB  - The efficacy and safety of a trial of labor after previous cesarean were
      evaluated in selected, low-risk women in a hospital-based birthing center staffed
      by certified nurse-midwives. A total of 303 low-risk women with one previous
      cesarean delivery underwent a trial of labor in the birthing center. A matched
      control, without a previous uterine incision, was selected for each study
      patient. Hospital charts of 298 matched pairs were available for analysis.
      Outcome measures included the requirement for intrapartum transfer to medical
      management, use of oxytocin, method of delivery, uterine scar separation, Apgar
      scores, birth weights, maternal febrile morbidity, and length of hospital stay.
      Intrapartum transfer to medical management was necessary in 26 (8.7%) study
      patients and 31 (10.4%) control subjects. The overall rate (98.3%) of vaginal
      birth after cesarean among study patients was not statistically different from
      the vaginal birth rate (99.3%) among control subjects. There were no differences
      in maternal or neonatal morbidity. The high percentage (84%) of study patients
      having had a previous uncomplicated vaginal birth after cesarean must be
      considered a potential limitation of the outcome data; however, the overall
      vaginal birth rate between study patients with and study patients without
      previous vaginal birth after cesarean was not statistically different. The latter
      group was more likely to require transfer to medical management and/or oxytocin
      augmentation. On the basis of these results, we concluded that for selected, low
      risk patients, a trial of labor after one previous cesarean may be managed safely
      and effectively by certified nurse-midwives in a hospital setting.

PMID- 9277063
TI  - ACNM accredited and preaccredited nurse-midwifery and midwifery education
      programs. Program information.

PMID- 9277062
TI  - Certified nurse-midwife and physician collaborative practice. Piloting a survey
      on the Internet.
AB  - This pilot study was designed to describe the clinical areas of collaboration,
      financial structures, and sources of conflict for certified nurse-midwives (CNMs)
      involved in nurse-midwife and physician collaborative practice (CP). A
      questionnaire was posted on an electronic bulletin board maintained by the
      Community-Based Nurse Midwifery Education Program of the Frontier School of
      Nursing. The nonrandom, convenience sample consisted of 78 respondents. Their
      mean age was 42 years; they had been in practice for a mean of 10 years, and 56%
      had graduate degrees. Eighty-nine percent reported involvement in CP. Eighty
      three percent co-managed higher-risk women, and 46% performed vacuum-assisted
      deliveries or were first assistants at cesarean sections. Forty-eight percent of
      CNMs did not bill in their own names, and only 12% had full hospital privileges.
      The most common sources of conflict in CPs were clinical practice issues (100%
      ever encountered), power inequities (92%), financial issues (66%), and gender
      relations (58%). Collaborative practice is a common form of practice for CNMs and
      suggests a model for collaboration in other sectors of the health care system.
      Future research should explore methods of reducing the potential for conflict
      between CNMs and physicians.

PMID- 9277064
TI  - Clinical bulletin no. 1--June 1996. Limited obstetrical ultrasound in the third
      trimester.

PMID- 9277065
TI  - Development and outcomes of the multiple-choice format national certification
      examination in nurse-midwifery and midwifery.
AB  - The national certification examination in nurse-midwifery and midwifery now is
      offered exclusively in the multiple-choice format. The strategies used to develop
      equivalent examination forms are described. The manner of criterion-referenced
      standard setting is explained. Outcomes of the first five multiple-choice
      examination forms include an aggregate first-time failure rate of 8.3%. Multiple-
      and logistic-regression analyses indicate that examination scores of African
      American and Hispanic ethnic candidates, and older candidates, are lower with
      regard to statistical significance; however, these differences are too modest to
      be of practical significance. No substantive relationship was observed between
      any demographic or academic variable and the probability of passing the
      examination. The experience gained by the ACNM Certification Council during
      development, administration, and evaluation of these first five multiple-choice
      examination forms has provided strong support for the transition to multiple
      choice testing for the assessment of entry into practice of this competency-based
      profession.

PMID- 9277066
TI  - Practice profile of members of the American College of Nurse-Midwives. Findings
      of a direct mail survey.
AB  - The scope of practice of today's nurse-midwife is much broader than that of the
      stereotypical "someone who specializes in delivering babies." Today's nurse
      midwife sees approximately 140 clients each month and is involved with providing
      care to the "total" client. This encompasses not only care related to pregnancy,
      but also well-woman gynecology, nutrition, mental wellness, and primary care.
      Although the majority of clients seen by CNMs are in their childbearing years,
      the practice of nurse-midwifery encompasses postmenopausal women as well. When
      comparing the results of this survey to responses to similar questions posed 3
      years earlier, practice size, number of births attended per month, years in
      practice, and types of conditions treated were answered in a similar fashion.
      Although the percentage of CNMs reporting pregnancy care activities remains
      virtually unchanged, a trend toward an increasing CNM role in well-woman
      gynecology and primary care is seen. About 5% more CNMs now state that well-woman
      gynecology and primary care are part of their monthly practice than did in the
      earlier survey. The biggest change in the greater number of CNMs reporting
      prescribing autonomy and authority over the 3-year period. In the earlier survey,
      51% of the polled CNMs reported full prescribing authority versus 84% who report
      full prescribing autonomy and authority in 1996. The prescriptions CNMs write
      each week reflect the diversity in their practice, ranging from those for
      antibiotics and antifungal agents to those for calcium supplements,
      antidepressants, and tranquilizers. For 19 of the 36 categories of
      pharmaceuticals included on the survey, at least half of all CNMs report having
      the opportunity to prescribe or order products during a "typical" week. In total,
      for these 36 categories, an average of 94 prescriptions/orders are written each
      week.

PMID- 9277067
TI  - A master's degree for entry-level ACNM-certified midwives. An option or
      necessity?
AB  - The health care industry is a massive system that is changing so rapidly that it
      is reinventing itself. With these changes, added demands have been placed on the
      knowledge base and practice of nurse-midwifery with emphasis on primary care,
      administration, and research as well as traditionally accepted nurse-midwifery
      practice. The American College of Nurse-Midwives (ACNM) has a history of being
      alert to consumer demands, sociopolitical forces, and the health care industry
      itself as stimuli for change after full dialogue with the membership and
      appropriate study. Because the ACNM Division of Accreditation will be requiring a
      baccalaureate degree upon entrance or completion of each midwifery education
      program by June 1999, dialogue should begin now about the benefits of requiring a
      masters degree as the entry-level credential.

PMID- 9277068
TI  - Mechanisms of drugs that affect uterine motility.
AB  - Modern obstetrics relies on a collection of drugs that affect the motility of the
      uterus either to stimulate or to suppress uterine contractions. Although a
      comprehensive, detailed understanding of how these drugs work does not yet exist,
      many, such as oxytocin, appear to work by altering cytosolic calcium levels in
      uterine smooth muscle cells. Other drugs, such as ritodrine, not only alter
      cytosolic calcium levels, but seem to inactivate myosin light chain kinase, a
      critical enzyme necessary for the initiation of uterine contractions. This report
      is intended to summarize the current state of knowledge regarding how these drugs
      affect the motility of the uterus. The delineation of the molecular mechanisms of
      action of these drugs is important because it provides the basis for their
      rational therapeutic use as well as for the design of new and better uterotrophic
      drugs.

PMID- 9277069
TI  - Acute renal failure (ARF) in Thailand. Retrospective analysis in a medical
      center.
AB  - The changing trend of today's ARF in Thailand had led to requirement of
      epidemiologic data for management and planning. Retrospective review of adult
      inpatient records for 5 years of Ramathibodi Hospital was performed. Normal
      initial serum creatinine rising to double its value within one week and/or
      oliguria were the inclusion criteria. Data from another 3 university hospitals
      were used for comparison. AFR is the second most common renal disease at
      Ramathibodi Hospital with sepsis as the major underlying etiology. Among 396
      cases of ARF, 194 were non-oliguric, 150 oliguric and 52 anuric. Non-oliguric
      cases needed lesser dialysis and had lower mortality. The number of AFR patients
      from 4 university hospitals varied from 0.14 to 0.18 per cent of hospital
      admission. If we consider the incidence of AFR in general hospital admission to
      be 0.1 per cent and the average hospital admission/year of Thailand was 3.25
      million, there will be 3,250 cases/year or 55 cases/million/population year. If 4
      dialyses/case was considered, 220 dialyses/ year/million population was required.
      We suggested that the hospitals of the province with population above 1 million
      should have a hemodialysis unit for both their local service and referral cases
      and all provincial hospitals should develop at least a peritoneal dialysis
      facility for increasing cases in ARF.

PMID- 9277070
TI  - Comparison of amphotericin B, flucytosine and itraconazole with amphotericin B
      and flucytosine in the treatment of cryptococcal meningitis in AIDS.
AB  - We compared amphotericin B (0.3 mg/kg/d) plus flucytosine (150 mg/kg/d) plus
      itraconazole (400 mg/d) (study group) with amphotericin B plus flucytosine
      (control group) by an open-randomized trial. In the study group, after CSF
      mycological cultures disclosed nothing, itraconazole was administrated alone
      through six weeks of treatment. Treatment was considered successful if the
      patient had two consecutive negative CSF cultures by the end of the 6-week
      treatment period. Fifty patients were enrolled in each group. There were
      significant differences between the study group and the control group in the
      successful treatment (100% vs 90%; P = 0.03), the mean length of time until
      normal body temperature after treatment (5.9 +/- 3.7 days vs 8.8 +/- 5.1 days; P
      = 0.02) and the adverse effects. The mean length of time to the first negative
      CSF culture was 13.9 +/- 6.1 days in the study group and 13.3 +/- 6.5 days in the
      control group (P = 0.66). Relapse rate with itraconazole 200 mg/day was higher in
      the study group.

PMID- 9277071
TI  - Sexually transmitted disease prevalence in brothel-based commercial sex workers
      in Chiang Mai, Thailand: impact of the condom use campaign.
AB  - One hundred and ninety five (195) brothel-based commercial sex workers (CSW) in
      Chiang Mai, Thailand, were screened for sexually transmitted disease (STD)
      between October 1994 and April 1995, prior to their enrollment in a multi-center
      comparative trial of the effectiveness of two strategies using male and female
      condoms. These CSW had a mean age of 22.2 (SD 4.3) years. Forty-seven per cent
      were Thai and 57.4 per cent had no formal education. Median duration of
      prostitution was 16 months and median cost for sexual service was 50 baht (US$ 2)
      per client. Ninety-four per cent of CSW reported always using condoms with
      clients. There were 63 (32.3%) CSW infected with at least one type of the STD
      screened. The prevalence of STD included chlamydial infection (16.9%), gonococcal
      infection (14.4%), condyloma accuminata (4.6%), moluscum contagiosum (2.6%) and
      trichomoniasis (1.0%). There was no statistically significant risk factor for STD
      found in this study. Despite an active programme for prevention of STD in CSW and
      the provision of free condoms, STD were diagnosed in one-third of the screened
      CSW in Chiang Mai. The programme needs to be strengthened by more intensive
      education and practice in the correct and consistent use of condoms and
      integrated with other STD prevention programmes.

PMID- 9277072
TI  - The mounting medical care cost for adult AIDS patients at the Faculty of
      Medicine, Siriraj Hospital: consideration for management.
AB  - From January 1993 to December 1995, case records of adult AIDS and HIV
      symptomatic patients admitted in the Department of Medicine, observation room and
      HIV Counseling Clinic were reviewed for the medical care cost of the patients
      based on the 1995 value of the Thai baht. In the three years, a total of 196, 227
      and 182 adult AIDS case were admitted as in-patients respectively. The median
      duration of admission was 14 days. The leading causes of admission were
      tuberculosis, cryptococcal meningitis, Pneumocystis carinii pneumonia, diarrhea,
      salmonellosis and toxoplasmosis. An increase in the number of AIDS patients in
      the observation room was observed: from 572 cases in 1993 to 1,205 cases in 1995.
      In addition, approximately 600 AIDS cases were followed up at four to eight week
      intervals. The analysis of the data found an average medical care cost for
      hospitalized patients to be 1,452 baht per day while in the observation room it
      was 1,509 baht per day and 1,132 baht per month for the patients attending the
      HIV and Counseling Clinic. Because of the higher number of cases and the limited
      number of admission beds, only 15 per cent of AIDS patients in the observation
      room could be admitted as hospitalized patients. At present, it is urgent that a
      referral network be established among all university hospitals, all government
      hospitals and health centers. In this way, the more advanced medical facilities
      can serve as a primary diagnostic center which can refer patients for care and
      follow-up based on an established referral system. In addition, the development
      of a hospice service and community care is needed for cases in the terminal stage
      of the illness.

PMID- 9277073
TI  - Azithromycin in non-gonococcal urethritis.
AB  - The efficacy and safety of a single 1 g oral dose of azithromycin was evaluated
      in 100 male patients with non-gonococcal urethritis (NGU). Enrolled were men with
      > or = 5 polymorphonuclear leukocytes (PMNL)/high power field (HPF) (x 1000
      magnification) in a Gram-stained smear of urethral discharge with or without
      symptoms and signs of NGU. Of the 66 evaluable patients, Chlamydia trachomatis
      was isolated from 18 cases (27.3%) and Ureaplasma urealyticum from 12 cases
      (18.2%). After treatment, signs and symptoms disappeared from 59 cases (89.4%).
      Forty-four cases (66.7%) showed reduced PMNL/HPF. C. trachomatis was eradicated
      in 18 cases (100%) and U. urealyticum in 12 cases (83.3%). One patient complained
      of mild dizziness, moderate nausea, and palpitations. Single 1 g oral dose of
      azithromycin appears to be effective and safe for treating chlamydial, non
      chlamydial, and ureaplasmal NGU. In addition, its ease of use encourages patient
      compliance.

PMID- 9277074
TI  - Slipped capital femoral epiphysis in Ramathibodi Hospital.
AB  - Slipped capital femoral epiphysis is rare in Asiatic Indonesian-Malays. Seven
      cases (9 hips) of this condition in Ramathibodi Hospital including five boys
      (average age, 12.5 years) and two girls (average age, 13 years) were reviewed.
      Most of the cases (4 out of 7) were acute on chronic and mild slips. No endocrine
      disorder was observed in all cases. All of the patients had a body weight above
      the mean of the normal population, four of which were obese. For the treatment, a
      single screw fixation including one case with cancellous and six cases with
      cannulated type were used. In the follow-up of average 2.5 years, six cases had
      satisfactory results. Avascular necrosis occurred in one case with mild and
      chronic slips in which a cancellous screw was used. It is concluded that obesity
      is the important factor related to the etiology in this study and probably is the
      same in other developing countries. The effect of a cancellous screw causing
      avascular necrosis is still questionable.

PMID- 9277076
TI  - Effect of intraoperative fluid on blood glucose level in neurosurgery.
AB  - There is a considerable controversy regarding glucose administration during
      intracranial surgery. However, recent animal and human studies suggest that
      hyperglycemia exacerbates ischemic brain damage and intraoperative hypoglycemia
      may not be a concern if the surgical procedure is less than 4 hours. We,
      therefore, studied the blood glucose in neurosurgery with craniotomy in 90 Thai
      patients, divided into 3 groups. 30 patients in each group received balanced salt
      solution (0.9% NSS), 5 per cent glucose rate 60-80 ml/h and 5 per cent glucose
      rate more than 120 ml/h. Blood for the determination of glucose concentration was
      obtained after induction and every 2 hours later until the end of the surgery.
      There was one male patient in group I who received balanced salt solution (0.9%
      NSS) had blood glucose concentration lowered to 57 mg% at 4 hours after
      induction. The patients in group II who received 5 per cent glucose solution at
      maintenance rate did not have hyperglycemia (161.20 +/- 38.30 mg%). In group III;
      patients given 5 per cent glucose infusion at the rate of more than 120 ml/h had
      hyperglycemia (236.75 +/- 63.57 mg%) at 6 hours. In conclusion, we suggest that
      in Thai patients undergoing neurosurgical procedures; blood glucose levels should
      be checked intraoperatively if glucose is withheld from the intraoperative fluid
      regimen. Otherwise 80 ml/h of 5 per cent dextrose intravenous infusion should be
      given to the patients to prevent hypoglycemia.

PMID- 9277075
TI  - Propofol vs isoflurane for neurosurgical anesthesia in Thai patients.
AB  - Sixty Thai patients, ASA class I-II, Glasgow coma score of 15 undergoing elective
      intracranial surgery were randomly assigned to 2 groups. In group I, 30 patients
      were induced with thiopental 3-5 mg/kg, intubation with succinylcholine 1-2 mg/kg
      and then maintained with 60 per cent N2O in O2, isoflurane and vecuronium as a
      muscle relaxant. In group II, 30 patients received fentanyl 50 micrograms,
      propofol 1.0-2.5 mg/kg for induction and vecuronium 0.08 mg/kg for intubation
      then maintained with 60 per cent N2O in O2, continuous infusion of propofol 2-12
      mg/kg/h and vecuronium as a muscle relaxant. Controlled ventilation in both
      groups was set to maintain PET CO2 in the range of 28-35 mmHg. 3 patients (1 in
      group I and 2 in group II) were excluded from the study due to surgical problems.
      There was no statistical difference in age, sex, ASA status, weight, duration of
      anesthesia. Group II had a more stable systolic BP, Diastolic BP and Pulse rate
      than Group I during induction and emergence from anesthesia. Glasgow coma scores
      in the recovery period, Group II had higher scores than Group I at 5 and 15
      minutes but not at 30 minutes. Mean recovery times (eye opening) was 14.03 +/-
      4.85 minutes in group I which is significantly different from 10 +/- 5.17 minutes
      in group II. The cost of anesthesia in group II was 1.3 times that of group I. In
      conclusion, although neurosurgical anesthesia for Thai patients with fentanyl
      propofol technique produces more stable blood pressure during intubation and
      emergence, rapid recovery from anesthesia and a higher Glasgow coma score, the
      cost of anesthesia is more expensive. Furthermore, this technique is more
      difficult and needs more experience.

PMID- 9277077
TI  - Radiofrequency catheter ablation in type I atrial flutter: preliminary experience
      of 10 cases.
AB  - Common atrial flutter results from macroreentry in the right atrium. Catheter
      ablation of slow conduction, between tricuspid annulus and inferior vena cava (TA
      IVC) or tricuspid annulus and coronary sinus ostium (TA-CS os) has been reported
      to terminate and prevent recurrence of this arrhythmia. We reported 10
      consecutive patients, 7 men and 3 women, who underwent radiofrequency catheter
      ablation of common atrial flutter. The mean age was 59.4 +/- 11.2 years (range 42
      82 years). During the paroxysmal atrial flutter, all patients had palpitation, 4
      had dyspnea on exertion, 3 patients had syncope and 1 patient had presyncope. The
      mean duration of symptoms was 5.7 +/- 4.9 years (range 0.5-13 years). Two
      patients had dilated cardiomyopathy, 1 Ebstein's anomaly and 1 chronic
      obstructive pulmonary disease. Four patients (40%) had history of atrial
      fibrillation (AF) before ablation. The mean cycle length of atrial rhythm was
      257.2 +/- 36.6 ms. Ablation was done by anatomical approach and could terminate
      arrhythmia in 9 patients (90%), 7 from TA-IVC, 2 from TA-CS os without major
      complication. The mean number of applications was 20.4 +/- 16.9 and turned atrial
      flutter to normal sinus rhythm in 13.5 +/- 10.7 seconds. Fluoroscopic and
      procedure times were 38.4 +/- 31.4 and 157.2 +/- 68.8 minutes, respectively.
      During the follow-up period of 24.0 +/- 28.7 weeks, 2 patients had recurrent
      atrial arrhythmia, 1 atrial fibrillation and 1 atrial flutter type I, giving the
      final success rate of 70 per cent. All patients who had recurrence or failure had
      a history of paroxysmal AF before ablation. In conclusion, radiofrequency
      catheter ablation in atrial flutter type I, using anatomical approach, is an
      effective treatment to terminate and prevent this arrhythmia in short term follow
      up. It may be considered as an alternative treatment in patients with atrial
      flutter who were refractory to antiarrhythmic agents.

PMID- 9277078
TI  - Clinicopathological features predicting recurrence of intracranial meningiomas.
AB  - A series of 11 recurrent meningiomas was studied. Most lesions occurred in women.
      The youngest patient was 17 years old and the oldest was 73 years. The mean age
      was 44 years. Multifactorial risk factors were involved in the tumor regrowth
      including age of patients, location of tumors, adequacy of initial surgery,
      certain histopathological features and subtypes of tumors. Tumors in young adults
      tended to have a rapid interval of regrowth as well as a tendency of multiple
      recurrences. Brain invasion, extensive bone and muscle involvement, foci of
      necrosis and hemorrhage, high mitotic index, angioblastic and papillary patterns
      were common pathological risk factors. Additionally, recurrent tumors may retain
      their original pathological appearance or become more aggressive by showing
      marked cellular pleomorphism. Area of liposarcomatous component was encountered
      in one recurrent lesion.

PMID- 9277079
TI  - The retroperitoneal approach for abdominal aortic aneurysms.
AB  - Graft replacement has become the reliable and effective form of treatment for
      abdominal aortic aneurysms (AAA). Operative therapy remains the major undertaking
      with significant rates of postoperative morbidity and mortality. The use of
      retroperitoneal approach has been proposed as an alternative to standard midline
      transabdominal approach. Over a 5 year period, 43 consecutive nonrandomized
      infrarenal AAA patients underwent elective surgical correction by the authors. 32
      patients with the mean age of 75 underwent transabdominal reconstructive
      procedures for AAA. The average size of AAA was 5.9 cm and operative time was 3
      hours and 25 minutes. The mortality rate was 6.25 per cent (2 of 32). The cause
      of death was myocardial infarction 1, and acute renal failure 1. There are many
      complications in the transabdominal group. 11 had prolonged ileus, 2 MI, 2 wound
      dehiscence, 2 atelectasis, 1 acute renal failure and 1 chylous ascites. In 11
      patients with retroperitoneal approach, the average size of AAA was 5.6 cm and
      operative time was 3 hours and 29 minutes. No operative mortality, the only 1
      complication was retroperitoneal hematoma. The most notable difference between
      the retroperitoneal group and transabdominal group was the speed and ease of
      postoperative recovery. The patients in the retroperitoneal group needed a
      shorter period of intubation, nasogastric drainage, stay in the intensive care
      unit and hospital. Patients in the retroperitoneal group also resumed oral
      alimentation sooner, shorter and smoother postoperative course. The patients in
      the retroperitoneal group had less blood loss and fewer transfusions than in the
      transabdominal group. Findings from our experience using the left retroperitoneal
      approach for a reconstructive procedure of AAA indicate that it results in fewer
      overall physiologic disturbances of the patients. We believe that the left
      retroperitoneal approach is a useful surgical access of choice for the elective
      repair of AAA.

PMID- 9277080
TI  - Balloon pulmonary valvuloplasty in children, one year follow-up experience at
      Ramathibodi Hospital.
AB  - Balloon valvuloplasty has become the treatment of choice in pulmonary valvular
      stenosis. The objective of this report is to review the experience of this
      procedure in children at the Department of Pediatrics, Ramathibodi Hospital in
      the past 4 years (1991-1994) with at least one year follow-up. During the study
      period, 19 children aged 2.1-14.3 years (mean 5.11 years) with the diagnosis of
      pulmonary valvular stenosis had successful pulmonary balloon valvuloplasty at
      this institution. The immediate peak systolic pressure gradient across the
      pulmonary valve by cardiac catheterization decreased from 92.05 +/- 46.92 to
      34.26 +/- 25.30 mmHg, by Doppler from 78.58 +/- 26.55 to 34.83 +/- 15.60 mmHg.
      Peak pressure gradient across the pulmonary valve by Doppler of the last
      examinations, one to 4 years after the procedure (mean 1.9 years), was 23.05 +/-
      9.40 mmHg in 17 patients. The mean ratio of balloon size and pulmonary valve ring
      was 1.06. One patient still has a residual gradient of 54 mmHg and two were lost
      to follow-up. No serious complication was encountered during the procedures.
      CONCLUSION: Balloon pulmonary valvuloplasty is effective in the management of
      children with valvular pulmonary stenosis. The intermediate term result is
      excellent.

PMID- 9277081
TI  - The Children's Depression Inventory as a screen for depression in Thai children.
AB  - This study examines the utilization of the Children's Depression Inventory (CDI),
      Thai version, as a screen for depression in Thai children. Subjects which
      consisted of 139 children aged 10-15 years filled out the CDI and were evaluated
      with structured psychiatric interview by a child psychiatrist who was blind to
      the results of the CDI. Children with interview validated depression had
      significantly elevated CDI scores (mean = 18.5, SD = 6.1) compared with
      nondepressed children (mean = 9.3, SD = 4.1), P > 10(-6). Furthermore, the CDI
      scores increased as the severity of depression increased. Using the Receiver
      Operating Characteristic Curve, a cut-point of 15 produced the best overall
      screening characteristics (sensitivity = 79%, specificity = 91% and accuracy =
      87%). The results of this study indicate that the CDI efficiently differentiated
      depressed from non-depressed children. Since the CDI is an economical, easy to
      adiminister and readily analyzable instrument, it should be used as a screen for
      depression and a supplant for clinical evaluation and follow-up in the treatment
      of depression in children.

PMID- 9277082
TI  - Two faces of nocturnal tongue biting.
AB  - Tongue biting associated with tonic/clonic movements of the limbs is common in
      epileptic patients, however nocturnal tongue biting as the only manifestation of
      epilepsy is rare. It can be found in frontal lobe epilepsy. Two cases with the
      same manifestation of nocturnal tongue biting were presented. One was the result
      of parasomnias-rhythmic movement disorders (RMD) and the other was a result of
      nocturnal frontal lobe epilepsy. The definite diagnosis of these abnormal
      nocturnal events was documented by prolonged EEG monitoring and polysomnography
      with simultaneous video studies. To our knowledge, RMD presenting with nocturnal
      tongue biting has never been reported in Thailand. Even in the foreign journals
      it has rarely been reported. It is crucial to make a definite diagnosis of RMD
      and nocturnal epilepsy to avoid overtreatment in the former and undertreatment in
      the latter. Symptomatology, diagnostic approach with therapy of these disorders
      were reviewed.

PMID- 9277083
TI  - Prediction of low bone mineral density in postmenopausal women by artificial
      neural network model compared to logistic regression model.
AB  - Measuring bone mineral density (BMD) is currently the best modality to diagnose
      osteoporosis and predict future fractures. The use of risk factors to predict BMD
      and fracture risk has been considered to be inadequate for precise diagnostic
      purpose, but it may be helpful as a screening tool to determine who actually
      needs BMD assessment. Recently, artificial neural network (ANN), a nonlinear
      computational model, has been used in clinical diagnosis and classification. In
      the present study, we evaluated the risk factors associated with low BMD in Thai
      postmenopausal women and assessed the prediction of low BMD using an ANN model
      compared to a logistic regression model. The subjects consisted of 129 Thai
      postmenopausal women divided into 2 groups, 100 subjects in the training set and
      the remaining 29 subjects in the validation set. The subjects were classified as
      having either low BMD or normal BMD by using BMD value 1 SD lower than the mean
      value of young adults as the cutoff point. Decreased body weight, decreased hip
      circumference and increased years since menopause were found to be associated
      with low BMD at the lumbar spine by logistic regression. For the femoral neck,
      increased age and decreased urinary calcium were associated with low BMD. The
      models had a sensitivity of 85.0 per cent, a specificity of 11.1 per cent and an
      accuracy of 62.0 per cent for the diagnosis of low BMD at the lumbar spine when
      tested in the validation group. For the femoral neck, the sensitivity,
      specificity and accuracy were 90.5 per cent, 12.5 per cent, and 69.0 per cent,
      respectively. Models based on ANN correctly classified 65.5 per cent of the
      subjects in the validation group according to BMD at the lumbar spine with a
      sensitivity of 80.0 per cent and a specificity of 33.3 per cent while it
      correctly classified 58.6 per cent of the subjects at the femoral neck with a
      sensitivity of 76.2 per cent and a specificity of 12.5 per cent. There was no
      significant difference in terms of accuracy, sensitivity and specificity in the
      prediction of low BMD at the lumbar spine or the femoral neck between ANN model
      and logistic regression model. We concluded that ANN does not perform better than
      convention statistical methods in the prediction of low BMD. The less than
      perfect performance of the prediction rules used in the prediction of low BMD may
      be due to the lack of adequate association between the commonly used risk factors
      and BMD rather than the nature of the computational models.

PMID- 9277084
TI  - Calcium and phosphate solubility curves for parenteral nutrient solutions
      containing Vaminolact.
AB  - Calcium and phosphate incompatibility in the total parenteral nutrient (TPN)
      solutions is a common problem especially in neonates. Their combinations in TPN
      admixture must be tested before use. We here investigated the compatibility of
      calcium and phosphate in TPN solutions containing a newborn amino acid product,
      Vaminolact. The TPN test-solutions contained 10 per cent dextrose, 1, 2, or 3 per
      cent Vaminolact, 4 mmole/L of magnesium sulphate and various combinations of
      calcium gluconate and dipotassium phosphate. Precipitations and crystallizations
      were inspected visually and microscopically after 24 hours standing at room
      temperature. Solubility curves were made by plotting the maximum concentrations
      of calcium and phosphate at which both were still compatible in the solution.
      Such curves are extremely helpful for clinicians and pharmacists to administer
      maximum calcium and phosphate dose for individual patient requirement.

PMID- 9277085
TI  - Functional endoscopic sinus surgery in patients with sinugenic headache.
AB  - Sixteen patients were operated on by functional endoscopic sinus surgery. Their
      principal complaint was facial pain or headache which was thought to be of
      sinugenic origin. These patients had no osteomeatal complex obstruction on
      diagnostic nasal endoscopy and also had unremarkable sinus diseases on computed
      tomography scan of paranasal sinuses. The operative procedures were very limited
      functional endoscopic sinus surgery which included middle meatotomies with
      uncinectomies and partial turbinectomies (frontoinferior). Ten patients (62.5%)
      had no headache postoperatively, and six patients (37.5%) had a reduction in
      severity. These patients also had a significant reduction in severity of
      associated nasal symptoms (yellow or green nasal discharge, nasal blockage,
      postnasal drainage, asthma, allergies). (p < 0.05) The pathophysiologic mechanism
      of facial pain or headache in these patients is probably related to reversible
      mucosal disease. This report focuses on a small group of select patients who had
      specific complaints and had underlying nasal mucosal disease in the form of
      allergy or vasomotor rhinitis. This therapy is not recommended for every patient,
      but only a small, selected group of patients who had classic complaints of sinus
      headache and had had medical treatment failures even if their nasal endoscopy and
      computed tomography scans were normal.

PMID- 9277086
TI  - Utilization of electron beam CT scan in diagnosis of pulmonary embolism.
AB  - Pulmonary embolism is a difficult entity to diagnose clinically and pulmonary
      angiogram has been the gold standard for the diagnosis. Our objective was to
      evaluate the usefulness of electron beam (Ultrafast) CT scan in aiding the
      diagnosis of such an entity, thus avoiding an invasive procedure. Between April
      1995 and March 1996 we prospectively studied 20 patients with clinical suspicion
      of pulmonary embolism by conventional perfusion scan of the lung, by invasive
      pulmonary angiography and by contrast enhanced electron beam CT scan. Simple
      statistic correlation between the 3 methods was obtained in regard to sensitivity
      and specificity utilizing the pulmonary angiogram as the gold standard. The
      sensitivity and specificity of contrast enhanced electron beam CT scanning was 95
      per cent and 100 per cent respectively. The correlation of positive and negative
      result of all three imaging modalities was 60 per cent. Contrast enhanced
      electron beam (Ultrafast) CT scan is a good alternative diagnostic modality for
      pulmonary embolism.

PMID- 9277087
TI  - Esophageal conduit in nearly hopeless corrosive esophageal stricture patient.
AB  - The case report of a 28 year old woman with strictured esophagus from corrosive
      esophagitis for 4 months is presented. Barium swallowing showed a strictured
      esophagus extending from T2 to the aortic knob and needed frequent dilatations.
      The patient had a perforated thoracic esophagus and mediastinitis on last
      dilatation. Cervical esophagostomy, transabdominal esophageal bandaging and
      jejunostomy feeding were done along with intravenous broad spectrum antibiotics.
      On esophagoscopy, there was complete stenosis of the cervical esophagus 2 cm from
      the postcricoid area. The large intestine from the caecum, transverse colon and
      descending colon was chosen as the esophageal conduit because of adequate length
      to pass subcutaneously. The caecum was anastomosed to the cervical esophagus and
      descending colon to the stomach. Seven days postoperatively, the patient could
      take liquids and soft porridge orally. There was a small leakage from the
      cervical anastomosed, spontaneous closure was achieved 3 weeks postoperatively.
      We chose the right side colon as the esophageal conduit because of adequate
      length to pass subcutaneously. Mediastinal and transhiatal routes could not be
      passed because of previous mediastinitis from thoracic esophageal perforation.
      This may be an alternative choice of operation for high cervical esophageal
      stenosis with previous mediastinitis.

PMID- 9277088
TI  - Malignant transformation in a benign encapsulated schwannoma of retropharyngeal
      space: a case report.
AB  - Malignant schwannomas are rare in the head and neck, however benign schwannoma of
      this area are common. Cases of malignant schwannoma have been reported in the
      nasal cavity, paranasal sinuses, eye, parapharyngeal space and neck with or
      without an association of von Recklinghausen disease. We described a case of an
      asymptomatic solitary malignant schwannoma arising in the retropharyngeal space
      which was treated by local excision and postoperative radiotherapy. To our
      knowledge, this case may be the first reported case in the world literature.

PMID- 9277089
TI  - Nonspecific immunity in diabetes: hyperglycemia decreases phagocytic activity of
      leukocytes in diabetic patients.
AB  - Phagocytic activity of leukocytes in blood was examined in 70 patients with
      diabetes mellitus. 40 of them had insulin-dependent diabetes--(IDDM) or type I,
      while there were 30 patients with noninsulin-dependent diabetes (NIDDM) or type
      II. Phagocytic activity of leukocytes was determined by quantitative method of
      ingestion, on the principle of quantifying phagocytized fungi (Saccharomyces
      cerevisiae) and free phagocytes (nonphagocytizing leukocytes) by means of a phase
      contrast microscope. The data have been statistically processed by the Student t
      test and variance analysis test (Duncan test). The index of phagocytosis amounted
      to 3.2 +/- 0.77 in diabetic patients, while it was 3.47 +/- 0.29 in healthy
      examinees from the control group, thus yielding a statistically significant
      difference, p < 0.05. Out of all examined parameters (blood glucose, glycosylized
      hemoglobin, mean glucose value) phagocytic activity of leukocytes showed a
      statistically significant correlation with mean value of glucose in blood.
      Patients with mean glucose value higher than 12 mmol/l showed a significantly
      lower index of phagocytosis (2.9 +/- 0.84) than patients whose mean glucose value
      was lower than 12 mmol/l (3.5 +/- 0.59), p < 0.05. Neither age and sex of the
      patients nor chronic complications caused by diabetes affected the phagocytic
      activity of leukocytes in diabetic patients. There was no significant difference
      in the phagocytic activity of leukocytes between patients with IDDM and those
      with NIDDM.

PMID- 9277090
TI  - Clinical research of dental erosion.
AB  - On the base of performed clinical studies of a possible appearance of dental
      erosion in patients, it can be concluded as follows: 1) Out of 710 treated
      patients, in 62 is found the appearance of erosive changes of dental tissues. 2)
      Erosive changes were more prevalent in patients in the third age group, more
      often in male than in female. 3) Patients with erosive changes are with
      distinctive gastrointestinal disorders, they used the hard toothbrush, soft food,
      and in most of them is noticed the appearance of psychic disorders with the
      aggressive behaving. 4) Studies have shown the justification and the need to
      continue them by multidisciplined approach in a higher number of patients, a
      longer period, in order for better discovering the aetiology of erosive changes
      of dental hard tissues.

PMID- 9277091
TI  - Ethical principles in health data protection.
AB  - Ethics, especially medical ethics, is of a great importance in health data
      protection, and in medical informatics field ethical principles have great
      importance in confidentiality, security, and access to patient records. This is
      not as simple problem as it looks in the first sight, and-in that context-it is
      significant that many jurisdictions have drafted laws in this regard. As medical
      informatics has been developed, this ethical problem is becoming very important
      for medical informatics. Many efforts to make fundamental principles "according
      to which data protection and access to official information could be reconciled"
      are made. The principles described in this paper are independent of any process,
      as they are based on ethical principles. It avoids any kind of conflict or
      misunderstandings. They can be a base for making of an ethical code for
      informatics in health care delivery. These principles are independent of any
      particular "laws", and they can serve as to establish uniformity of standards in
      medical informatics.

PMID- 9277092
TI  - Vinylchloride monomer exposure by the plastic industry workers basic condition
      for liver angiosarcoma appearance.
AB  - The retrospective study of vinylchloridemonomer (VCM) exposure at 37 workers in
      the period from 1969 till 1987 was done, average time of exposition was 1.843 +/-
      1.105 h, average VCM concentration was 543 +/- 228 ppm and average total exposure
      amount ("cumulative concentration of VCM") was 1.103811 +/- 1.050 766 ppmh at the
      time of autoclave cleaning 0.4 +/- 0.1 h. According updata investigations, high
      VCM concentration is essential for liver angiosarcoma (ASL) occurrence although
      the length of exposure is of concern. The possibility of new cases of
      angiosarcoma of liver is warned about.

PMID- 9277093
TI  - Experiences in the use of multimedia software in medical education.
AB  - In the realm of computers for education it has always been the case that the
      imagination of the programmers and educationalist has demanded the more
      innovative facilities which were never present in the machines in current use but
      which were promised in the next generation. Whilst the educationalists did
      pioneering work with what they had, they could always see how a package could be
      improved with the next generation of hardware. Now the hardware can give them
      everything they need; but they will always want more. Sensible use of multi-media
      can prove to be useful in training all levels of workers within healthcare. It
      can combine the best of the text-book and the video, but above all the use of
      interaction should produce untold benefits.

PMID- 9277094
TI  - [Age-dependent changes in dynamic body balance as evaluated by the body tracking
      test (BTT)].
AB  - Stability of posture and gait is improved by growth and decays with aging.
      Maturational changes and deterioration of static posture with aging have been
      determined by using gravic body sway tests. In this study, we constructed a new
      system, the Body Tracking Test (BTT), to evaluate dynamic body balance function
      as opposed to static balance. Preliminary results of the study were previously
      reported elsewhere. Healthy volunteers of various ages (total, 516 persons) were
      subjects of the study. The principle of the BTT is for the subject to attempt to
      track an optical moving target displayed on the computer screen by shifting his
      or her body center of gravity that was also displayed on it. The target moved for
      a span of 15 cm horizontally on the 14-inch screen. The movement was lateral and
      antero-posterior (horizontal and vertical) in direction at a constant velocity of
      0.125 Hz. The recording was for 60 seconds. In BTT the gain for target against
      tracking was fixed to 2.0 (target: tracking = 1: 2). The target was 100 cm
      anterior to the platform where the subject was to stand erect with the feet close
      together. The criteria for evaluation of the tracking function were determined by
      our preliminary study, the principle of which was to judge the rate of accordance
      of the tract of the moving target with that of body tracking. The score was
      divided into five ranks from A to E. We called it "The 5 grade evaluations of
      tracking ability". Age-dependent changes in the score were obtained and the
      statistical significance of the value was determined by chi 2 analysis. With
      regard to both the lateral and antero-posterior tracking abilities, there was an
      apparent improvement by maturation. The high school students reached the adult
      level in lateral tracking but not in antero-posterior tracking ability. Also, the
      tracking ability started to deteriorate after age 40. It is apparent from this
      study that the balancing or dynamic postural control differs between youth and
      the elderly, i.e.; lateral control seems to improve faster in youths and older
      persons tend to balance better in the antero-posterior directions. The BTT
      requires visual as well as proprioceptive information for its function. Moreover,
      dynamic maintenance and shifting of muscular tone and strength are prerequisite.
      In addition, for BTT, reflective postural control is strongly aided by training
      in terms of efficiency and skills that require higher cerebral functions. The BTT
      described here thus appears to represent a cumulative effect of the sensory,
      visual, motor and higher cerebral functions.

PMID- 9277095
TI  - [Sensorineural hearing loss caused by middle ear surgery].
AB  - It is well known that sensorineural hearing loss rarely occurs after middle ear
      surgery. Five cases of postoperative sensorineural hearing loss were reviewed.
      These operations amounted to 0.9% of all middle ear operations in which the first
      author was involved. The causes of hearing loss were believed to be labyrinthitis
      through the fistula in cholesteatoma case 1, and acoustic trauma from the bone
      cutting burr in cases 2 and 3. In cases 4 and 5 postoperative sensorineural
      hearing loss occurred several months after stapes surgery and the causes of
      hearing loss were unknown. On the basis of the available literature discussion
      focused on management of labyrinthine fistula, the acoustic effect of the bone
      cutting burr and the possibility of sensorineural hearing loss caused by stapes
      surgery.

PMID- 9277097
TI  - [Long-term observation of sensorineural hearing-impaired children with hearing
      aids].
AB  - In the long-term observation (9-22 years) of 45 hearing-impaired children, using
      our own "Hearing Test Progress Table", 36(80.0%) showed fluctuation of the
      hearing threshold. Twenty-nine of the 36 patients had acute progression of
      hearing loss. Three peaks of onset of the acute loss were observed: at age 6, 10,
      16 years in girls, 7, 11 and 16 years in boys. Twenty-three of the 45 (51.1%)
      have been able to maintain their good thresholds throughout these periods, with
      14 cases of hearing loss restored by our successful treatment of acute
      sensorineural hearing losses (1-6 times). Twenty-two of the 45 children (48.9%)
      could not maintain their initial thresholds: gradual hearing deterioration in 7
      of the 22, and acute hearing loss (1-10 times) in the remaining 15 cases.
      Although these 15 patients could not maintain their initial hearing thresholds
      until the end of the observation period, active treatments for their acute losses
      were successful in the early period, and almost all patients were able to
      maintain their initial hearing thresholds until graduation from elementary
      school. Our "Hearing Test Progress Table" is based on the results of pure tone
      audiometry for each frequency on every audiometry test. The management (including
      guidance and treatment) using the table is very effective.

PMID- 9277096
TI  - [Effect of intravenous injection of lidocaine HCl on evoked otoacoustic emissions
      in tinnitus case].
AB  - This study was performed to examine the influence of lidocaine HCl on evoked
      otoacoustic emissions (EOAE) in tinnitus case. EOAE were recorded before and
      after intravenous injection of lidocaine HCl in 19 patients with unilateral
      tinnitus. EOAE amplitudes were significantly increased after injection of
      lidocaine HCl for 10 minutes. Between the effective group and the non-effective
      group of lidocaine HCl for tinnitus, significant differences were recognized
      after injection of lidocaine HCl for 10 minutes. These results suggested that
      lidocaine HCl stimulated cochlear mechanics. Significant differences were not
      recognized at any time between the group of hearing loss with unknown origin, the
      group of Meniere's disease and the group of tinnitus without hearing loss.

PMID- 9277098
TI  - [The chronological changes in the size of maxillary defect].
AB  - Use of a maxillary prosthesis is now considered one of the good methods to
      ameliorate the crippling caused by the defect in the maxillary palate area after
      an ablative procedure for a maxillary tumor and it consumes no physical resources
      from the patient. There has been debate on whether the prosthesis should be made
      in the very early postoperative days or after the wound is stabilized. In this
      study, changes in the area of the defect in the palate after surgery were
      investigated by using plaster models from clinical cases we have experienced.
      Twenty-one cases were investigated according to the following features:
      "maxillary sinus cancer "+" more than 1.5 years of follow-up for maxillofacial
      prosthetics "+" presence of more than two casts of the case". These casts were
      photographed from a distance of 1.5 m, and the photographs were enlarged to the
      original size of the cast, then the defect area was measured with a Planimeter
      (Uchida Co. Ltd). The area of the defect had shrunk in 16 cases. It took over 1
      year to get stabilized in 80% of the cases. It is believed to take around 3.5
      years for all cases to become stable. This tendency had no relationship with the
      pattern of the defect, the stroke of the mouth opening, the pattern of the rest
      of the teeth, or the defect area itself. These findings suggest that it may be
      advisable to start the prosthetic work as early as possible rather than waiting
      for stability of the defect wound, to improve the patients's QOL.

PMID- 9277099
TI  - [Vertical oculomotor disorders in progressive supranuclear palsy and spino
      cerebellar degeneration].
AB  - We performed neuro-otological investigation of vertical oculomotor disorders in
      35 patients with degenerative disease [progressive supranuclear palsy (PSP) and
      spino-cerebellar degeneration], and obtained the following results: 1) In the
      patients with PSP, in addition to vertical oculogyric disorder both saccade and
      pursuit eye movements were disturbed, and the disturbance of saccade movement was
      greater. Even the patients without an oculogyric disorder were all found to have
      decreased saccade velocity, suggesting that this disorder may occur earliest in
      PSP. 2) In olivo-ponto-cerebellar atrophy (OPCA), saccade movement was less
      disturbed than that in PSP. In contrast, pursuit movement was disturbed more
      frequently. 3) In late cortical cerebellar atrophy (LCCA), vertical ocular
      movement was hardly disturbed compared with OPCA. 4) Concerning dentate nuclear
      degeneration, we cannot reach a conclusion because of the few cases studied, but
      a variety of oculomotor disorders were seen; both saccade and pursuit movements
      were disturbed, but saccade movement was less disturbed than in PSP. 5) In visual
      suppression tests, enhancement in the light area was frequently seen in the
      patients with PSP and OPCA, but none with LCCA showed such change. In addition,
      enhancement of the light area under visual suppression was significantly
      correlated with vertical oculomotor disorder.

PMID- 9277100
TI  - [En bloc resection of the temporal bone for middle ear carcinoma extending to the
      cranial base].
AB  - En bloc resection of the temporal bone for squamous cell carcinoma of the middle
      ear was performed by the postauricular transtemporal and retromastoid approaches.
      The patient was a 70-year-old woman whose tumor extended to the middle and
      posterior cranial fossae. Temporal and retromastoid craniotomies were carried
      out, then the temporal dura and the cerebellar dura, and the transverse and
      sigmoid sinuses were exposed. The temporal dura and the cerebellar dura were
      opened, and the transverse sinus was ligated at the junction with the sigmoid
      sinus. After that, the tentorial dura was incised, the incision extending
      anteriorly to the middle cranial fossa and transecting the superior petrosal
      sinus. Consequently, a wide view into the middle and the posterior cranial fossae
      was obtained. In the posterior fossa, cranial nerves VII and VIII were divided.
      On the other hand, nerves IX, X and XI were preserved at the dural incision on
      the posterior surface of the temporal bone. Subsequently, in the area of the
      carotid canal, the temporal bone was drilled toward the medial side of the
      internal auditory canal and also posteriorly down to the jugular bulb. At this
      stage, the temporal bone and the soft tissue attachments, such as the middle and
      posterior cranial fossa dura, and the sigmoid sinus, were separated from the
      pyramidal apex and the clivus. The dural defect was repaired with a free
      pericranial graft. A rectus abdominis muscle flap was transferred to reconstruct
      the defect of the skull base resulting from the temporal bone resection.
      Postoperative complications like CSF leakage, meningitis and lower cranial nerve
      damage, were not seen after the treatment. The patient has shown no evidence of
      recurrence for the 28 months since the surgical treatment, and has not complained
      of any problems with swallowing or conducting conversations in daily life. With
      the contribution of recent developments in skull base and reconstruction surgery,
      more aggressive en bloc resection of the temporal bone can be carried out on
      patients with advanced middle ear carcinoma. These developments will also make it
      possible for patients whose prognosis was previously thought to be poor to have a
      chance for a cure.

PMID- 9277101
TI  - [Investigation of the usefulness of CYFRA 21-1 as a tumor marker in squamous cell
      carcinomas of the head and neck].
AB  - It has been demonstrated that CYFRA 21-1 (ELISA kit), which recognizes the
      soluble cytokeratin 19 fragment, is useful for assessing circulating tumor
      antigens in sera of patients with lung cancer. In this study, we compared the
      clinical significance of this new marker with the established squamous cell
      carcinoma antigen (SCC Ag), using sera from patients with head and neck malignant
      disease, healthy controls, and supernatants of established cell lines derived
      from squamous cell carcinomas and adenocarcinomas. The subjects were: Group A, 39
      patients with malignant disease of the head and neck. Group B, 11 patients
      considered to be tumor-free after treatment. Group C, 67 patients with benign
      disease or healthy volunteers. Culture supernatants: 11 cell lines established
      from squamous cell carcinomas and adenocarcinomas. Serum levels of CYFRA 21-1 and
      SCC Ag of group A were significantly higher than those of group C. This finding
      suggests that CYFRA 21-1 is useful as a tumor marker as well as SCC Ag. CYFRA 21
      1 and SCC Ag levels of patients in group A at the early and progressive stages of
      disease were comparable to the levels in group C. Both tumor markers are
      therefore useful for diagnosis of in the early stage of cancer. We attempted to
      set a cut-off level of CYFRA 21-1. The sensitivity of CYFRA 21-1 is higher than
      that of SCC Ag, especially in patients in the early stage of the disease. This
      finding indicates that the CYFRA 21-1 is preferable to SCC Ag as a tumor marker
      for the diagnosis of patients even in the early stages of malignant disease. The
      levels of CYFRA 21-1 in culture supernatants derived from tumor cell lines are
      higher than those of SCC Ag in all cell lines. The levels of CYFRA 21-1 are
      measurable, with levels varying with the cell line. There appears to be no
      correlation between the level of CYFRA 21-1 and the character of the cell lines,
      but this issue remains to be further investigated.

PMID- 9277102
TI  - [Studies on structure and mechanism of action of heat-stable enterotoxin].

PMID- 9277103
TI  - [Signal transduction across the cytoplasmic membrane by the Escherichia coli
      chemoreceptors].

PMID- 9277106
TI  - [Wide occurrence of enterohemorragic Eschrichia coli O157 in natural freshwater
      environment].
AB  - Recent outbreaks of hemorrhagic colitis by Escherichia coli O157 urge us to
      clarify the source, distribution, and fate of those pathogens. We hypothesized
      that E. coli O157 enter into viable but nonculturable state (VBNC) so that the
      conventional culture method fails to detect those strains from natural
      environment. In the microcosm using sterilized river water, E. coli O157
      gradually lost their viability. Total count using epifluorescent microscopy and
      the direct viable count (DVC), however, stayed almost constant for more than a
      month, indicating that the cells fell into the VBNC state. In order to see the
      distribution of E. coli O157 in natural environment, the DVC method and
      fluorescent antibody technique were applied. All river water samples from five
      different places in and near Tokyo metropolitan area showed occurrence of cells
      reacted with the antibody applied. This indicates that E. coli O157 may be widely
      distributed in freshwater environment as normal inhabitants. The understanding of
      VBNC state of E. coli O157 should be essential to investigate on the behavior of
      this pathogen in nature and find out a suitable method to prevent from further
      outbreaks.

PMID- 9277105
TI  - [Escape mechanism of Listeria monocytogenes in relation to host immune response].

PMID- 9277104
TI  - [Action of clostridial neurotoxins and mechanism of the membrane fusion of
      intracellular transport vesicles].

PMID- 9277107
TI  - [An autobacteriographic study on distribution and localization of methicillin
      resistant Staphylococcus aureus in the immunosuppressed mice].
AB  - Cyclophosphamide (CY, 250 mg/kg) was intraperitoneally administered to mice. Four
      days after, a rifampicin-resistant strain of methicillin-resistant Staphylococcus
      aureus (MRSA, S. aureus 1-6 RFPr) was intravenously inoculated at the level of
      10(7) cfu/mouse. Distribution and localization of the inoculated organism were
      chronologically investigated by means of whole body autobacteriography. CY (100
      mg/kg) was consecutively administered for 4 days following the inoculation. As a
      result, dense colonies of the organism were detected from many organs and
      tissues, that is, the liver spleen, gastrointestinal tract, kidneys, urinary
      bladder and bone (bone marrow) on the day after the inoculation. Following 3 days
      after the inoculation, the distribution and localization in CY-treated mice
      remained substantially unchanged and some animals died. It is demonstrated that
      in an experimental mouse model of MRSA infectious disease under immunosuppressed
      condition, the inoculated organism can stand still and proliferate not only in
      the gastrointestinal tract but also in the urinary tract and lymphhemopoietic
      organs.

PMID- 9277108
TI  - [Diagnosis of shunt dysfunction after transjugular intrahepatic portosystemic
      shunt by color Doppler ultrasonography: usefulness change of maximum flow
      velocity in portal vein].
AB  - To clarify whether color doppler ultra sonography (CDUS) is useful for the
      diagnosis of shunt dysfunction after transjugular intrahepatic portosystemic
      shunt (TIPS), we investigated CDUS in 20 patients who were diagnosed as shunt
      dysfunction and 12 patients with patent shunt by follow-up portal pressure
      measurements. In patients with shunt dysfunction, maximum flow velocity in the
      portal vein (PV-Vmax) and maximum flow velocity in the shunt were significantly
      decreased in comparison to just after TIPS placement, but not in patients with
      patent shunt. Grade of color image of the shunt flow and flow direction in the
      portal vein branches were not significantly different between the shunt
      dysfunction group and the patent shunt group. Comparing the just after TIPS to
      the follow-up phase, the decreasing rate of PV-Vmax was negatively correlated
      with the increasing rate of portal vein pressure caused by shunt dysfunction.
      CDUS could detect shunt dysfunction in 95% sensitivity, 83% specificity and 91%
      overall accuracy on the basis of a diagnostic criterion for shunt stenosis : more
      than 40% decrease of PV-Vmax from just after TIPS insertion. These results
      suggest that follow-up observation using CDUS is useful for the diagnosis of
      shunt dysfunction after TIPS procedure, and PV-Vmax is an especially important
      indicator to detect shunt dysfunction.

PMID- 9277109
TI  - [Numerical aberration of chromosome 17 is correlated with multiple primary cancer
      in colorectal carcinoma].
AB  - Numerical aberration of chromosome 17 of 14 cases of colorectal carcinoma with
      multiple primary cancer (: multiple cancer) was compared with that of 35 cases of
      colorectal carcinoma without any other cancer (: single cancer). Fluorescence in
      situ hybridization with p17H8 was performed on touch smear from fresh materials.
      The proportion of aneusomy 17 (NCAI: numerical chromosome aberration index) in
      multiple cancers was significantly higher than that of single cancers (37.7 +/-
      10.5% VS 46.1 +/- 8.0%; p < 0.01). Although NCAI of single cancers conformed to
      cancer progression (26.1 +/- 4.7% in Dukes A, 33.1 +/- 7.1% in Dukes B, 39.9 +/-
      6.9% in Dukes C, and 45.7 +/- 12.0% in Dukes D), that of multiple cancers was
      high in all stages (44.7 +/- 7.3%, 44.4 +/- 6.8%, 50.4 +/- 11.2%, and 49.6 +/-
      5.6%, respectively). Furthermore, the multiple numerical aberration of chromosome
      17 in multiple cancers was more often than that of single cancers (64.3% VS
      22.9%; p < 0.01).

PMID- 9277110
TI  - [Effects of NSAIDs and PGE1 analogue on the permeability of human small
      intestine].
AB  - We studied permeability of human small intestine to clarify the following
      questions. 1) Does indomethacin increase intestinal permeability (IP)? 2) Does
      ornoprostil (PGE1 analogue) prevent the increased IP due to indomethacin? 3) Does
      acemetacin (pro-drug) increase IP? Eleven healthy volunteers were studied before
      and after ingestion of indomethacin, acemetacin, ornoprostil. After an overnight
      fast, they drank an isotonic solution containing 1.5 g rhamnose and 10.5 g
      lactulose. IP was estimated with lactulose/rhamnose percentage excretion in urine
      for 5 hours. An administration of indomethacin (75 mg) for one day increased IP
      significantly, and the coadministration of indomethacin and ornoprostil showed no
      significant change in IP compared with those of controls. Pro-drug administration
      did not increase IP. It is suggested that simultaneous administration of
      ornoprostil prevent the mucosal damage caused by indomethacin clinically, and
      that the mechanism of this increase IP is due to lack of mucosal prostaglandins
      on the small intestine.

PMID- 9277112
TI  - [A case of multiple gastric ulcers associated with Candida infection].

PMID- 9277111
TI  - [Simple ulcer of the ileocaecal region associated with thyroid cancer, report of
      a case].

PMID- 9277113
TI  - [A case of Echinostoma hortense infection diagnosed by the upper gastrointestinal
      endoscopy].

PMID- 9277115
TI  - [A case of the hepatocellular carcinoma with obstructive jaundice due to the
      tumor thrombus in the common hepatic duct].

PMID- 9277114
TI  - [A case of epithelioid hemangioendothelioma of the liver disseminated to the
      peritoneum--a review of the cases in Japan].

PMID- 9277116
TI  - [A case report of pedunculated hepatocellular carcinoma, and review of case
      report in the literature].

PMID- 9277117
TI  - [A case of pancreatic pseudocyst with hematemesis by fenestration into the
      stomach and hemosuccus pancreaticus].

PMID- 9277118
TI  - [Role of coagulant cancer antigen 1, tissue factor, and HLA-DR in the
      procoagulant activity of human gastric cancer cell lines].

PMID- 9277119
TI  - [Intraductal ultrasonographic angiography for evaluation of biliary disease].

PMID- 9277120
TI  - Industry perspective on inspections and enforcement.

PMID- 9277121
TI  - The importance of pharmaceuticals in the health services in the 21st century.

PMID- 9277122
TI  - Total organic carbon method for aspirin cleaning validation.
AB  - Cleaning validation is the process of assuring that cleaning procedures
      effectively remove the residue from manufacturing equipment/facilities below a
      predetermined level. This is necessary to assure the quality of future products
      using the equipment, to prevent cross-contamination, and as a World Health
      Organization Good Manufacturing Practices requirement. We have applied the Total
      Organic Carbon (TOC) analysis method to a number of pharmaceutical products. In
      this article we discuss the TOC method that we developed for measuring residual
      aspirin on aluminum, stainless steel, painted carbon steel, and plexiglass. These
      are all surfaces that are commonly found as part of pharmaceutical production
      equipment. The method offers low detection capability (parts per million levels)
      and rapid sample analysis time. The recovery values ranged from 25% for aluminum
      to about 75% for plexiglass with a precision of 13% or less. The results for the
      plexiglass tended to vary with the age of the surface making the determination of
      an accurate recovery value difficult for this type of surface. We found that the
      TOC method is applicable for determining residual aspirin on pharmaceutical
      surfaces and will be useful for cleaning validation.

PMID- 9277123
TI  - Preparation and evaluation of bacterial stocks for filter validation.
AB  - Bacterial cell stock paste of Brevundimonas diminuta (American Type Culture
      Collection # 19146) used for filter validation was evaluated by standard
      microbiological procedures to determine culture purity, monodispersion, cell
      size, and strain identity. Tests performed included direct microscopic count,
      standard plate count, gram stain, streak plate, sizing by microfiltration,
      scanning electron microscopy, and biochemical identification. Results indicated
      the bacterial stocks were of consistent quality in terms of bacteriological
      purity, cell size, viability, and concentration. Sizing by microfiltration
      confirmed consistent monodispersion and cell retention characteristics for each
      lot tested. Use of the commercially available RapID NF Plus system confirmed each
      lot to be B. diminuta as indicated by biochemical profile and identification
      database. These tests represent parameters necessary for qualification of
      bacterial stocks to be used for filter validation.

PMID- 9277125
TI  - Setting alert/action limits for environmental monitoring programs.

PMID- 9277124
TI  - Enhancing effect of nonionic surfactant on the inactivation of lipopolysaccharide
      by steam-heat treatment II.
AB  - n-alkylpolyoxyethylene surfactants (CnH2n+1O(CH2CH2O)mH; CnEm) showed a strong
      enhancing effect on the inactivation of lipopolysaccharide (LPS) by heat
      treatment over a wide range of temperatures. The effect of CnE8 (n = 10-16) was
      observed above the critical micelle concentration (CMC) and above the cloud
      point, and was influenced by the length of the alkyl chains. The efficacy of the
      surfactants was in the order C10E8 < C12E8, C16E8 < C14E8. However, the
      hydrophilic moiety seemed to have no influence. An 80-95% solution of n-butanol
      showed a similar effect, indicating that LPS was more effectively inactivated in
      the oily phase of the surfactants than in water. The effect of surfactant on the
      hydrodynamic diameter of LPS was the same before and after steam-heat treatment
      for 20 minutes at 121 degrees C. Each surfactant disaggregated LPS without
      alteration of the activity of LPS before the heat treatment. We consider that the
      surfactants interact with LPS in the region of lipid A in a manner that favors
      loss of the activities of LPS during heating.

PMID- 9277126
TI  - Industry perspective on the proposed changes to the GMPs.

PMID- 9277127
TI  - Excipients and their use in injectable products.
AB  - Formulation of a new drug product with excipients, that have been previously
      added to an approved injectable product, may save pharmaceutical companies
      developmental time and cost. The Physicians' Desk Reference (PDR) and Handbook on
      Injectable Drugs were reviewed, extracting all information on excipients. The
      information was consolidated into eight tables, categorizing excipients as 1)
      Solvents and Co-solvents, 2) Solubilizing, Wetting, Suspending, Emulsifying or
      Thickening agents, 3) Chelating Agents, 4) Antioxidants and Reducing Agents. 5)
      Antimicrobial Preservatives, 6) Buffers and pH Adjusting Agents, 7) Bulking
      Agents, Protectants, and Tonicity Adjustors, and 8) Special Additives. Where
      applicable, tables list frequency of use, concentration, and an example of a
      commercial product containing the excipient. Excipients which are included in the
      1996 FDA 'Inactive Ingredient Guide,' but do not appear in the PDR or Handbook on
      Injectable Drugs, were included as a separate list.

PMID- 9277128
TI  - Release of soluble nucleotidases: a novel mechanism for neurotransmitter
      inactivation?

PMID- 9277129
TI  - The cross-talk between nitric oxide and Ca2+: a story with a complex past and a
      promising future.

PMID- 9277130
TI  - Stress, hormonal changes, alcohol, food constituents and drugs: factors that
      advance the incidence of tobacco smoke-related cancer?
AB  - The genotoxicity of the most potent carcinogen in cigarette smoke [4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)] is dependent on the
      relationship between its activation by cytochrome P450 enzymes and its
      detoxification by carbonyl reduction to NNK alcohol (NNAL) followed by
      glucuronidation. Recently, '11 beta-hydroxysteroid dehydrogenase' (11 beta-HSD 1)
      was identified to be responsible for NNK carbonyl reduction. It is now speculated
      that differences in tissue expression of 11 beta-HSD 1, as well as genetic
      polymorphisms, may have profound influences on the organospecificity and potency
      of NNK-induced cancerogenesis. Moreover, endogenous and exogenous substrates or
      inhibitors of 11 beta-HSD 1 may shift the NNK/NNAL equilibrium and favour NNK
      toxification in a variety of physiological and therapeutic situations. These
      issues are discussed here by Edmund Maser, who also describes how recent
      observations could provide the experimental base for epidemiological or clinical
      studies, which focus on polymorphisms in 11 beta-HSD 1 enzyme expression, as well
      as on implications of exposure to 11 beta-HSD 1 modulators and concurrent
      smoking.

PMID- 9277131
TI  - Endocytosis and recycling of G protein-coupled receptors.
AB  - Agonist stimulation of G protein-coupled receptors causes a dramatic
      reorganization of their intracellular distribution. Activation of receptors
      triggers receptor endocytosis and, since receptors recycle back to the surface
      continuously, a new steady state is reached where a significant proportion of
      receptors is located internally. Although this movement of receptors is
      remarkable, its role has been enigmatic. Recent developments have provided
      insight into the compartments through which the receptors move, the nature of the
      signals that trigger receptor translocation, and the significance of receptor
      cycling for cell function. In this article, Jennifer Koenig and Michael Edwardson
      review recent progress in this field and place receptor cycling into a
      mathematical framework that reveals the extent and rate of intracellular receptor
      movement.

PMID- 9277132
TI  - Synthetic functions of airway smooth muscle in asthma.
AB  - Studies now show that the airway smooth muscle cell, in addition to its
      contractile function, can participate in and coordinate the inflammatory
      response. In response to inflammatory cytokines, the airway smooth muscle cell
      produces cytokines, chemokines, growth factors and cell adhesion molecules
      leading to inflammatory cell chemotaxis, hyperplasia and hypertrophy. Anti
      inflammatory mediators are also produced suggesting a dual role in inflammation.
      Moreover, in response to growth stimuli the cells may adopt a phenotype more
      suited to 'synthetic' function. These issues are discussed in this article by
      Simon Johnson and Alan Knox, who also point to ways in which some of these
      pathways offer future therapeutic potential in asthma.

PMID- 9277133
TI  - The orphan opioid receptor and its endogenous ligand--nociceptin/orphanin FQ.
AB  - Following the elucidation of the amino acid sequences of the mu-, delta- and
      kappa-opioid receptors, a new 'orphan opioid receptor' was cloned with a high
      degree of homology to the 'classical' opioid receptors. The endogenous opioid
      peptides show little or no activity at this new receptor; however, a novel
      endogenous peptide for the orphan opioid receptor has been isolated and
      sequenced. Here, Graeme Henderson and Sandy McKnight review recent findings on
      this new receptor and its endogenous ligand, and address the contentious issue of
      whether activation of this receptor results in hyperalgesia or analgesia.

PMID- 9277134
TI  - Design of peptides, proteins, and peptidomimetics in chi space.
AB  - Peptide and protein biological activities depend on their three dimensionals
      structures in the free state and when interacting with their receptors/acceptors.
      The backbone conformations such as alpha-helix, beta-sheet, beta-turn, and so
      forth provide critical templates for the three-dimensional structure, but the
      overall shape and intrinsic stereoelectronic properties of the peptide or protein
      important for molecular recognition, signal transduction, enzymatic specificity,
      immunomodulation, and other biological effects depend on arrangement of the side
      chain groups in three-dimensional chi space (their chi 1, chi 2, etc. torsional
      angles). In this paper we explore approaches to the de novo design of
      polypeptides and peptidomimetics with biased or specific
      conformational/topographical properties in chi space. We consider computational
      and experimental methods that can be used to examine the effects of specific
      structural modifications in constraining side chain groups of amino acid residues
      and their similarities in chi space to the natural amino acids to evaluate what
      sort of mimetics are likely to mimic normal amino acids. We then examine some of
      the asymmetric synthetic methods that are being developed to obtain the amino
      acid mimetics. Finally, we consider selected examples in the literature where
      these specialized amino acids have been incorporated in biologically active
      peptides and the specific insights they have provided regarding the topographical
      requirements for bioactive peptide potency, selectivity, and other biochemical
      and pharmacological properties. Constraints in chi space show great promise as
      useful tools in peptide, protein, and peptidomimetic de novo design of structures
      and pharmacophores with specific stereostructural, biochemical and biological
      properties.

PMID- 9277135
TI  - Simultaneous two-photon activation of type-I photodynamic therapy agents.
AB  - The excitation and emission properties of several psoralen derivatives are
      compared using conventional single-photon excitation and simultaneous two-photon
      excitation (TPE). Two-photon excitation is effected using the output of a mode
      locked titanium: sapphire laser, the near infrared output of which is used to
      promote nonresonant TPE directly. Specifically, the excitation spectra and
      excited-state properties of 8-methoxypsoralen and 4'-aminomethyl-4,5,8
      trimethylpsoralen are shown to be equivalent using both modes of excitation.
      Further, in vitro feasibility of two-photon photodynamic therapy (PDT) is
      demonstrated using Salmonella typhimurium. Two-photon excitation may be
      beneficial in the practice of PDT because it would allow replacement of visible
      or UV excitation light with highly penetrating, nondamaging near infrared light
      and could provide a means for improving localization of therapy. Comparison of
      possible laser excitation sources for PDT reveals the titanium: sapphire laser to
      be exceptionally well suited for nonlinear excitation of PDT agents in biological
      systems due to its extremely short pulse width and high repetition rate that
      together provide efficient PDT activation and greatly reduced potential for
      biological damage.

PMID- 9277136
TI  - Anthraquinone photonucleases: a surprising role for chloride in the sequence
      neutral cleavage of DNA and the footprinting of minor groove-bound ligands.
AB  - Irradiation of water-soluble anthraquinone (AQ) reagents in the presence of
      chloride ions results in the spontaneous, sequence-neutral cleavage of DNA.
      Mechanistic studies indicate that cleavage is initiated by chlorine atoms,
      produced by charge transfer interaction between chloride anion and AQ triplet
      states. High-resolution gel electrophoresis suggests that cleavage arises from
      abstraction of a hydrogen atom from C-4' of deoxyribose units. The targeting of
      this hydrogen, which is located in the minor groove of duplex DNA, can be
      effectively blocked by netropsin and, to a lesser degree, berenil, leading to
      photofootprinting of these minor groove-binding drugs.

PMID- 9277137
TI  - Far-UV-induced dimeric photoproducts in short oligonucleotides: sequence effects.
AB  - Cyclobutane pyrimidine dimers and pyrimidine(6-4)pyrimidone adducts represent the
      two major classes of far-UV-induced DNA photoproducts. Because of the lack of
      appropriate detection methods for each individual photoproduct, little is known
      about the effect of the sequence on their formation. In the present work, the
      photoproduct distribution obtained upon exposure of a series of dinucleoside
      monophosphates to 254 nm light was determined. In the latter model compounds, the
      presence of a cytosine, located at either the 5'- or the 3'-side of a thymine
      moiety, led to the preferential formation of (6-4) adducts, whereas the cis-syn
      cyclobutane dimer was the main thymine-thymine photoproduct. In contrast, the
      yield of dimeric photoproducts, and particularly of (6-4) photoadducts, was very
      low upon irradiation of the cytosine-cytosine dinucleoside monophosphate.
      However, substitution of cytosine by uracil led to an increase in the yield of (6
      4) photoproduct. It was also shown that the presence of a phosphate group at the
      5'- end of a thymine-thymine dinucleoside monophosphate does not modify the
      photoproduct distribution. As an extension of the studies on dinucleoside
      monophosphates, the trinucleotide TpdCpT was used as a more relevant DNA model.
      The yields of formation of the thymine-cytosine and cytosine-thymine (6-4)
      photoproducts were in a 5:1 ratio, very close to the value obtained upon
      photolysis of the related dinucleoside monophosphates. The characterization of
      the two TpdCpT (6-4) adducts was based on 1H NMR, UV and mass spectroscopy
      analyses. Additional evidence for the structures was inferred from the analysis
      of the enzymatic digestion products of the (6-4) adducts of TpdCpT with
      phosphodiesterases. The latter enzymes were shown to induce the quantitative
      release of the photoproduct as a modified dinucleoside monophosphate in a highly
      sequence-specific manner.

PMID- 9277138
TI  - Potential involvement of both type I and type II mechanisms in M13 virus
      inactivation by methylene blue photosensitization.
AB  - We have investigated the mechanism of virus photoinactivation with methylene blue
      (MB) by conducting deuterium oxide (D2O), azide ion (N3-) and oxygen-dependent
      studies. Inactivation of M13 bacteriophage and singlet oxygen (1O2) generation by
      MB photosensitization were irradiation dose dependent. Inactivation of M13 was
      enhanced by D2O and inhibited by N3-, suggesting that 1O2 participates in M13
      inactivation by MB photosensitization. However, N3- did not inhibit M13
      inactivation completely. On the other hand, deoxygenating the reaction solution
      still caused 52-67% of M13 inactivation observed in the presence of oxygen. These
      results suggest that 1O2-mediated (Type II) and sensitizer-mediated (Type I)
      reactions may both play roles in M13 inactivation by MB photosensitization.

PMID- 9277139
TI  - The role of protein kinase C activity in the killing of Chinese hamster ovary
      cells by ionizing radiation and photodynamic treatment.
AB  - In several recent studies it has been shown that protein kinase C (PKC) activity
      may either potentiate or antagonize cell killing by different cytotoxic agents.
      These apparently conflicting observations suggest that the effects of PKC
      activity on cell survival may depend on the different properties of different
      cell types but do not exclude the possibility that the effects may also depend on
      the nature of the cytotoxic agent. In this context the effects of PKC activation
      and PKC inhibition or down-regulation on Chinese hamster ovary (CHO) cell
      survival after photodynamic treatment and ionizing radiation were studied. It
      appeared that PKC activation by short-term incubation with 12-O-tetradecanoyl
      phorbol-13-acetate (TPA) protected CHO cells against ionizing radiation but, in
      contrast, sensitized the cells to photodynamic treatment. Conversely, inhibition
      of PKC by H7 and down-regulation of PKC activity by prolonged incubation with TPA
      sensitized CHO cells to ionizing radiation but protected the cells against
      photodynamic treatment. These results demonstrate that in one particular cell
      type PKC activity may have opposite effects on cell survival following cellular
      damage, depending on the nature of the cytotoxic agent.

PMID- 9277140
TI  - Photoreaction of new psoralen analogs with DNA: sequence and mutation specificity
      in the Escherichia coli lacZ gene.
AB  - New thio- and seleno-analogs of psoralen were synthesized and analyzed for their
      photoreactivity toward DNA. Using oligonucleotides of defined sequence, we first
      showed that these derivatives predominantly generated interstrand crosslinks at
      5'-TpA sites. We also observed a surprisingly high reactivity of 7H
      thiopyrano[3,2-f][1]benzofuran-7-one (PSO[O-S]) with the BamHI and PstI
      oligomers, giving rise to the formation of crosslinks at 5'-ApT sites and of the
      thymidine-psoralen-cytosine type. Next, the sequence specificity in the
      photochemical binding of all the compounds was investigated in two DNA fragments
      encompassing the lacZ gene of Escherichia coli, using the T4 DNA polymerase
      sequencing methodology. Resulting maps demonstrated that thio- and seleno-analogs
      of psoralen preferentially photoreacted with thymine and cytosine residues. The
      AT-rich sequences proved to be particularly reactive sites as did adjacent
      thymines, especially at C-surrounding residues. Likewise, photoaddition at
      cytosines in CA/AC context was observed. It was highly significant that all of
      the derivatives exhibited similar sequence specificities with only minor
      differences. However, PSO(O-S) differed from the other heteropsoralens.
      Photoadducts occurred with a higher frequency at AC and CA dinucleotides, and new
      sites were detected. A comparison with 8-methoxypsoralen photobinding is also
      reported. Finally, the mutagenic consequences of photoadducts induced in M13mp19
      DNA by PSO(O-S) were determined in a forward system that detects all classes of
      mutagenic events. The high phototoxicity exhibited by PSO(O-S) could be
      attributed to crosslinks, and the comparison of the observed mutational
      specificity with the photoadduct distribution within the same gene showed that
      mutations were targeted at potential monoadduct sites where photolesions were
      detected in our footprinting experiments.

PMID- 9277141
TI  - Correlation between site II-specific human serum albumin (HSA) binding affinity
      and murine in vivo photosensitizing efficacy of some Photofrin components.
AB  - Human serum albumin (HSA) is one of the key components in human blood that may
      influence drug distribution. As such, it is important to know the affinity of any
      drug for albumin. Previously, Photofrin, a mixture of monomeric, dimeric and
      oligomeric porphyrins, has been subjected to HSA binding studies. However, due to
      its complex nature, binding studies on Photofrin or other hematoporphyrin
      derivatives with HSA are inconclusive. In this report, the binding properties of
      some components (dimers and trimers) of Photofrin and the relationship between
      murine photosensitizing efficacy and those binding properties were investigated.
      The interaction of these porphyrins with HSA was investigated by direct
      ultrafiltration and fluorescent titration techniques with fluorescent probes such
      as dansyl-L-proline (DP), which is known to interact selectively with site II on
      HSA. Porphyrins also were tested for antitumor activity in a mouse model
      following intravenous administration and exposure to laser light. Together, the
      results suggest that the photosensitizers that were preferentially bound to site
      II of HSA were most effective at controlling murine tumor regrowth.

PMID- 9277142
TI  - Fluorescence lifetime imaging of experimental tumors in hematoporphyrin
      derivative-sensitized mice.
AB  - Tumor detection has been carried out in mice sensitized with hematoporphyrin
      derivative (HpD) by measuring the spatial distribution of the fluorescence
      lifetime of the exogenous compound. This result has been achieved using a time
      gated video camera and a suitable mathematical processing that led to the so
      called "lifetime images." Extensive experimental tests have been performed on
      mice bearing the MS-2 fibrosarcoma or the L1210 leukemia. Lifetime images of mice
      show that the fluorescence decay of HpD is appreciably slower in the tumor than
      in healthy tissues nearby, allowing a reliable detection of the neoplasia. The
      lengthening of the lifetime in tumors depends little on the drug dose, which in
      our experiments could be lowered down to 0.1 mg/kg body weight, still allowing a
      definite tumor detection. In order to ascertain the results achieved with the
      imaging apparatus, high-resolution spectroscopy, based on a time-correlated
      single photon counting system, has also been performed to measure the
      fluorescence lifetime of the drug inside the tumor and outside. The outcomes
      obtained with two techniques are in good agreement.

PMID- 9277143
TI  - An assay for the quantitation of Photofrin in tissues and fluids.
AB  - A method for determining the concentration of Photofrin in tissues and biological
      fluids was developed. The procedure is based on the dissolution of biological
      material with Solvable, a commercially available tissue solubilizer, followed by
      porphyrin-specific fluorescence detection and measurement. It was found necessary
      to use a quadratic standard curve for the estimation of unknown Photofrin
      concentrations. While this method is limited to compounds that are stable in
      strong base, it has the advantages of being sensitive, rapid and low cost.

PMID- 9277144
TI  - Photobiological properties of methylene violet.
AB  - The interaction of methylene violet (MV) and 4-bromomethylene violet (BrMV) with
      calf thymus and supercoiled phi X174 phage RF I DNA is reported. Measurements
      employing UV-visible absorption spectroscopy and equilibrium dialysis give
      evidence for the formation of complexes by each dye with DNA in the dark. They
      covalently bind to DNA, and MV nicks DNA, when the nucleic acid/dye mixtures are
      irradiated with visible light in a deoxygenated environment. Quantum efficiencies
      for singlet oxygen formation are 0.27 and 0.25 for MV and BrMV, respectively. A
      higher value (0.49) is observed for 4-iodomethylene violet (IMV).

PMID- 9277145
TI  - Diamino acid derivatives of porphyrins penetrate into yeast cells, induce
      photodamage, but have no mutagenic effect.
AB  - The yeast Saccharomyces cerevisiae was used as a model eukaryotic organism to
      study the uptake of diamino acid derivatives of porphyrins and their
      phototoxicity with particular emphasis on possible mutagenic effects. The water
      soluble hematoporphyrin derivatives diarginate (HpD[Arg]2) and 1-arginin di(N
      amino acid)-protoporphyrinate used in this study are effective photosensitizers
      in tumor photodynamic therapy. Depending on the amino acid substituent, the
      porphyrin derivatives differ in their affinity for yeast cells. It is shown that
      HpD(Arg)2 and PP(Met)2 (Arg)2 penetrate into the yeast cell and are metabolized.
      Both compounds sensitize yeast cells to photodamage but have no mutagenic effect
      on nuclear or mitochondrial genomes.

PMID- 9277146
TI  - Sun exposure, sunscreen and their effects on epidermal Langerhans cells.
AB  - This study examined the effects of chronic and current sun exposure on the number
      of Langerhans cells in epidermal sheets of UV-exposed and unexposed skin of the
      arms and assessed the effect of sunscreens. Participants were enrolled in a skin
      cancer prevention trial and had been using sunscreen daily for the previous 3
      years. There were significantly fewer Langerhans cells on the exposed (463
      cells/mm2) than on the unexposed forearm (528 cells/mm2) (P = 0.0001). High sun
      exposure in the previous 2 weeks and a history of predominantly outdoor
      occupations were both associated with a reduced number of Langerhans cells,
      although age and other biological indicators of chronic exposure were not
      associated. Sunscreen use was protective against the effects of current but not
      chronic sun exposure, with a suggestion of a greater effect at higher levels of
      exposure. Unexpectedly, people with a past history of nonmelanoma skin cancer had
      more Langerhans cells in both the exposed and the unexposed skin. These results
      emphasize the need for continued public health education to protect the immune
      system from the damaging effects of UV radiation.

PMID- 9277147
TI  - Increased photosensitivity in HL60 cells expressing wild-type p53.
AB  - Loss of p53 function has been correlated with decreased sensitivity to
      chemotherapy and radiation therapy in a variety of human tumors. Comparable
      analysis of p53 status with sensitivity to oxidative stress induced by
      photodynamic therapy has not been reported. In the current study we examined
      photosensitivity in human promyelocytic leukemia HL60 cells exhibiting either
      wild-type p53, mutated p53 or deleted p53 expression. Experiments were performed
      using a purpurin, tin ethyl etiopurpurin (SnET2)-, or a porphyrin, Photofrin (PH)
      based photosensitizer. Total SnET2 accumulation was comparable in all three cell
      lines. Uptake of PH was highest in cells expressing wild-type p53 but incubation
      conditions could be adjusted to achieve equivalent cellular PH levels during
      experiments that analyzed photosensitivity. Survival measurements demonstrated
      that HL60 cells expressing wild-type p53 were more sensitive to PH- and SnET2
      mediated photosensitization, as well as to UVC irradiation, when compared to HL60
      cells exhibiting deleted or mutated p53 phenotypes. A rapid apoptotic response
      was observed following purpurin- and porphyrin-induced photosensitization in all
      cell lines. Results of this study indicate that photosensitivity is increased in
      HL60 cells expressing wild-type p53 and that photosensitizer-mediated oxidative
      stress can induce apoptosis through a p53-independent mechanism in HL60 cells.

PMID- 9277148
TI  - Chronically ultraviolet-exposed human skin shows a higher mutation frequency of
      mitochondrial DNA as compared to unexposed skin and the hematopoietic system.
AB  - Normal ageing processes are associated with an accumulation of mutations within
      the mitochondrial (mt) DNA. The most frequent mutation is a 4977 base pair (bp)
      deletion known as common deletion. In order to test the hypothesis that
      chronically sun-exposed skin is characterized by an increased mutation frequency
      of mtDNA, the mutation frequency of the common deletion between skin and another
      replicating tissue (the hematopoietic system) and chronically sun-exposed versus
      sun-protected skin was compared in the same individuals. This was done by
      comparing the amount of mutated mtDNA molecules with the whole mitochondrial
      genome in the same specimen with a semiquantitative polymerase chain reaction
      method, thus allowing direct comparison of different tissues. In all skin
      specimens the common deletion could be observed. In contrast only 3 of 10 blood
      samples revealed detectable amounts of the common deletion. Comparison of sun
      exposed versus sun-protected skin exhibited a higher content of the common
      deletion in sun-exposed skin in 7 of 10 individuals. Additionally, a hitherto
      undescribed mtDNA mutation was detected exclusively in human skin. These studies
      indicate that exposure of human skin to solar radiation leads to an accumulation
      of mtDNA mutations, possibly via oxidative damage, which may play an important
      role in photoageing.

PMID- 9277149
TI  - Characterization of DNA damage inflicted by free radicals from a mutagenic
      sunscreen ingredient and its location using an in vitro genetic reversion assay.
AB  - We describe an in vitro approach to assessing the potential genotoxicity of
      illuminated sunscreens. The photomutagenic sunscreen Padimate-O attacks DNA on
      illumination with simulated sunlight, producing strand breaks and lesions that
      are labile to N,N'-dimethylethylenediamine but few, if any, cyclobutane dimers or
      other direct photoproducts. The damage can be completely suppressed by the free
      radical quenchers Tris, ethanol, mannitol and dimethylsulfoxide, which is
      commonly used as a solvent in conventional photomutagenicity assays. Using a
      genetic reversion assay that depends on regenerating beta-galactosidase activity
      in photodamaged plasmids we find that GC base pairs are particularly susceptible
      to attack by Padimate-O.

PMID- 9277150
TI  - Structure-activity and mechanism studies on silicon phthalocyanines with
      Plasmodium falciparum in the dark and under red light.
AB  - Syntheses for the new photosensitizers HOSiPcOSi(CH3)2(CH2)3N(CH1)1 or 3(CH3)2,
      Pc 34 and Pc 25, have been developed and the order of activity of these
      photosensitizers and the previously reported photosensitizer Pc 4,
      HOSiPcOSi(CH3)2(CH2)3N(CH3)2, in the dark and with broad-band red light toward
      Plasmodium falciparum in red blood cell (RBC) suspensions has been studied. The
      order of activity has been found to be Pc 4 > Pc 34 > Pc 25. Thus, the activity
      of the photosensitizers under both sets of conditions is inversely proportional
      to the length of their terminal amino alkyl chains. The 50% inhibition dye
      concentration (IC50) in the dark for the parasites in RBC suspension with Pc 4 is
      24 nM and the dye concentration and light fluence that yield > or = 3 log10 of
      parasite inactivation with Pc 4 are 2 microM and 3 J/cm2, respectively. The
      synthesis of DNA and proteins by the parasites in culture was strongly inhibited
      by Pc 4 in the dark while parasite lactate dehydrogenase (pLDH) activity was
      unaffected. With Pc 4 and light, DNA and protein synthesis of the parasites in
      culture was strongly inhibited, pLDH activity of the parasites was moderately
      inhibited and ribosome density of the parasite cells was reduced. Gel
      electrophoresis studies showed that synthesis of all parasite proteins was
      inhibited to a similar extent. These results suggest that Pc 4 both in the dark
      and with light inactivates the cells by disturbing their machinery for the
      synthesis of not just one but a whole series of proteins. It is concluded that Pc
      4 and light may be able to serve as a practical sterilization combination not
      only for HIV and other viruses but also for malaria parasites in RBC
      concentrates, and that Pc 4 by itself may have potential as a chemotherapeutic
      agent toward malaria.

PMID- 9277151
TI  - An unexpected spectrum of p53 mutations from squamous cell carcinomas in
      psoriasis patients treated with PUVA.
AB  - Photochemotherapy employing 8-methoxypsoralen and long-wavelength ultraviolet
      radiation (UVA, 320-400 nm) is widely used in the treatment of psoriasis. The
      photoactivation of psoralens in skin cells leads to formation of DNA photoadducts
      which may be responsible, at least in part, for the efficacy of these
      photochemotherapies. However, mutations arising from these adducts may also lead
      to the well-characterized increased incidence of squamous cell carcinoma.
      Mutations in the p53 tumor suppressor gene have been detected in many human
      cancers. To determine whether p53 mutations occur in squamous cell carcinomas in
      PUVA patients, PCR was used to amplify the exons (5-9) in which other studies
      have found a high frequency of point mutations. Gel electrophoresis was used to
      detect single-strand conformational polymorphisms. Aberrantly migrating bands
      were excised, reamplified and sequenced. Thirty-four specimens from 10 patients
      were examined. Specimens from one patient who had received no phototherapy as
      well as from normal controls were also analyzed. Five of the 10 patients showed
      at least one p53 mutation. In contrast to previously reported psoralen-induced
      p53 mutations in mice, the expected psoralen type mutations at alternating AT
      sites were not detected. All but two of the altered sequences occurred at
      dipyrimidine sites which is typical of solar type mutations. Two C-->T mutations
      and two dipyrimidine mutations (CC-->TT) were found. Other mutations included: C-
      >G, G-->T, C-->A and an 18 bp deletion. A review of therapeutic history of these
      patients showed that some had also received UVB phototherapy. Furthermore,
      because sunlight is thought to be beneficial for psoriasis, nontherapeutic,
      casual UVB exposure cannot be excluded. Our observations suggest that the SCC may
      have arisen from the solar mutations and that PUVA may enhance tumor progression
      or immune suppression.

PMID- 9277152
TI  - Independent medical examinations. Analyzing IME reports for workers compensation
      cases.

PMID- 9277153
TI  - Proper disease classification in breast implant cases.

PMID- 9277154
TI  - A comparison of nurse education in the USA with the situation in the UK.

PMID- 9277155
TI  - Project 2000: a new preparation for practice--has policy been realized? Part I.
AB  - Project 2000 was established in the UK in 1984. The project report, published 2
      years later, embraced the whole of the educational system for nursing, midwifery
      and health visiting. It is useful, 10 years on, to note what actually happened in
      what became an enormous undertaking and the biggest ever change in nursing,
      midwifery and health visiting training. But how well were policy formulation and
      implementation planned? Has the policy process been successful? What are the
      outcomes to date? This policy review chronicles policy initiation and
      formulation, decisions within the political system and policy outputs,
      implementation and outcomes in the context of the environment, using a
      combination of two policy models as the guiding framework. The focus is on
      implementation in England. The extent to which the original proposals in the
      project report have been realized is identified, together with policy changes and
      additions which occurred during the policy process. This macro-review of the
      whole of the policy process avoids the common faults of separating policy
      initiation from its implementation, or policy content from policy process. The
      record will enable past actions and events to be taken into account in the
      context of future plans for the 21st century.

PMID- 9277156
TI  - Implications of computer networking and the Internet for nurse education.
AB  - This paper sets out the history of computer networking and its use in nursing and
      health care education, and places this in its wider historical and social
      context. The increasing availability and use of computer networks and the
      internet are producing a changing climate in education as well as in health care.
      Moves away from traditional face-to-face teaching with a campus institution to
      widely distributed interactive multimedia learning will affect the roles of
      students and teachers. The use of electronic mail, mailing lists and the World
      Wide Web are specifically considered, along with changes to library and
      information management skills, research methods, journal publication and the
      like. Issues about the quality, as well as quantity, of information available,
      are considered. As more and more organizations and institutions begin to use
      electronic communication methods, it becomes an increasingly important part of
      the curriculum at all levels, and may lead to fundamental changes in geographical
      and professional boundaries. A glossary of terms is provided for those not
      familiar with the technology, along with the contact details for mailing lists
      and World Wide Web pages mentioned.

PMID- 9277157
TI  - Accreditation of prior learning: is it worth it? An evaluation of a pilot scheme.
AB  - Accreditation of Prior Learning (APL) is a relatively new process for both
      students and colleges of nursing and claims to offer many benefits (Open
      University 1990, Fox et al 1992). This paper describes the findings of a study
      undertaken to determine students' experiences of the APL process and their
      perceptions of how the APL process developed them. A sample of 14 students
      reported on the use of APL to obtain academic credit for a Level I Welsh National
      Board Framework Module. The results indicated both some difficulties and benefits
      associated with using the APL process. The majority of students experienced
      difficulty in reflecting on prior learning and practice. This seemed to be due in
      part to the students' reluctance to value their clinical learning experiences.
      Many of the sample also reported difficulty in maintaining motivation over the
      period of time allocated to complete the APL process. All the students undertook
      the process in their own time and had to submit the module summative assignment
      in addition to the APL evidence required. These factors may have further
      influenced motivational levels. Clear positive outcomes were that APL was felt to
      be a worthwhile process, even increasing self-esteem for some individuals. It
      also enabled students to develop reflective writing skills and to value clinical
      experience. Recommendations were made to both facilitate and enhance the APL
      experience for future students, and to promote critical reflection within the
      nursing profession as a whole.

PMID- 9277158
TI  - Humanist ideology and nurse education. I. Humanist educational theory.
AB  - Nurse education is dominated by the humanist perspective and the educational
      theory that it generates. Following a brief description of the perspective's
      phenomenological foundations and definition of humanist ideology, humanist
      educational theory is illustrated in an outline of the key contributions of John
      Dewey, Carl Rogers, Malcolm Knowles and Paulo Freire. The article concludes by
      noting Freire's sociological challenge to the individualism of the humanist
      perspective. This challenge recognizes the ideological and social control role of
      education in securing the reproduction of power relations and leads to
      questioning the function of individualism and the interests that humanist
      ideology may serve.

PMID- 9277159
TI  - Humanist ideology and nurse education. 2. Limitations of humanist educational
      theory in nurse education.
AB  - This article questions the viability of humanist educational theory in nurse
      education and raises the issue of which interests are served by humanist
      ideology. The limitations of the humanist approach are traced. Self-directed
      learning is shown to be problematic in nurse education, leading to tensions
      between independent learning and required course content, and the appropriateness
      of student-centred learning to the professional education of nurses is queried.
      The need to produce safe practitioners compromises the humanist model. Lifelong
      learning, for example, becomes institutionalized, and its self-directed character
      transformed into a mandatory process of lifelong professional education. The
      humanist model has become the new orthodoxy in nurse education and operates as a
      form of social control. Through its individualism the approach supports a
      competency model, which in turn restricts the potential diversity of 'product'.
      This individualistic bias denies the social reality of nursing and fails to
      empower the nurse by emphasizing individual growth at the expense of social
      learning. The article concludes that humanist ideology serves the needs of a free
      market philosophy. If nurse education is to be challenging it must break with
      individualism and seek to develop a different rationale, that of a collectivist
      ideology.

PMID- 9277160
TI  - Issues facing nurse teachers on the pre-registration diploma of higher education
      course (Project 2000): a case study approach.
AB  - This paper draws on the experience and expertise of nurse practitioners and
      teachers of nurses to report on significant issues facing the latter in their
      work. The findings form part of a larger study describing major changes in the
      role and work of nurse teachers resulting from Project 2000 initiatives. The
      rationale for adapting a case study approach is outlined. The results indicate
      that changes in the work of nurse teachers and diversity of activities expected
      has placed some major obstacles in their work. Nurse teachers were perhaps
      inadequately prepared for their new roles, given the haste required by the
      demonstration nursing schools in their curricular submission documents in order
      to compete for approved course recognition (Project 2000) and demonstration
      status. The study recommends extensive staff support, development and academic
      growth, and continuing commitment to steady progress and change.

PMID- 9277161
TI  - Nurse education: a feminist approach.
AB  - Nursing is predominantly a female profession. This paper seeks to explore the
      implications of this for curriculum design and suggests that insights from
      feminist theory should be applied to curricula. To insert the 'subject' of
      feminism into the curriculum is different from allowing its theories to affect
      the design of the curriculum itself. The paper seeks to justify such a change and
      asks what the resulting characteristics would be. Would such a curriculum change
      succeed and what would be its limitations? The paper concludes by highlighting
      the implications for nurse education.

PMID- 9277162
TI  - The variety of qualitative research. Part one: Introduction to the problem.
AB  - For a number of reasons qualitative techniques have taken firm root in nursing
      research generally and are of growing importance in research undertaken by nurse
      educators. But there is a great deal of confusion about the nature of the data
      which are produced by qualitative research, the way such data must be handled,
      and the use to which such data can be put. The confusion often results from a
      failure to differentiate between several orientations to qualitative data.
      Positivist research may use qualitative data (something not always recognized).
      It presupposes that there is some underlying, true, unequivocal reality, and a
      theory covering this is to be sought by the research. There must be evidence of
      validity-in the sense of a match between the data and the reality they are
      supposed to reveal. Non-positivist research is of a number of kinds, despite
      often being treated as unified. These will be treated in the second part of this
      paper.

PMID- 9277163
TI  - The variety of qualitative research. Part two: Non-positivist approaches.
AB  - For a number of reasons qualitative techniques have taken firm root in nursing
      research generally and are of growing importance in research undertaken by nurse
      educators. But there is a great deal of confusion about the nature of the data
      which are produced by qualitative research, the way such data must be handled,
      and the use to which such data can be put. The confusion often results from a
      failure to differentiate between several orientations to qualitative data. In the
      previous paper Positivist research was discussed. Non-positivist research is of a
      number of kinds, despite often being treated as unified. Examples are: (a)
      descriptive ('phenomenological') research-which seeks to give a faithful account
      of an area of experience or of an aspect of the 'life-world'; (b) interpretative
      ('hermeneutic') research-which aims to show ways of making sense of experience;
      and (c) discourse analysis-which draws out the socially available modes of
      thinking and action which reveal themselves in qualitative data.

PMID- 9277164
TI  - Shared learning for primary health care teams: a success story.
AB  - This paper sets out an educational model for shared learning for professionals
      working in primary health care teams (PHCTs). It presents an outline of an
      experiential educational programme using a simulated learning exercise based on a
      genogram. Multidisciplinary programmes are inherently problematic and tend to be
      ad hoc in their choice of educational theory. It was therefore our intention to
      discover the educational principles and theory that underpinned our innovative
      educational experience and to offer some fundamental criteria for the planning of
      future shared learning sessions in PHCTs. The process chosen to make the theory
      explicit was, 'reflecting on a critical incident' (Reed & Proctor 1993, Tripp
      1993).

PMID- 9277165
TI  - Link teacher behaviours: student nurses' perceptions.
AB  - The role of the nurse teacher in the clinical area is a major issue in nurse
      education today. When attempting to define the role, identification of teacher
      behaviours that are effective and valued by students is essential. Whilst there
      is no shortage of literature addressing nurse educationalists' opinions of the
      nature of the present and future role, there is a paucity of papers reflecting
      students' views, and UK students in particular. The aim of this descriptive
      survey was to discover the views of third year RGN diploma level student nurses
      regarding the link teacher behaviours that help them to learn. One hundred and
      two student nurses completed a written questionnaire seeking information about
      the number and length of link teacher visits, and ratings of the level of
      helpfulness of 5 categories of link teacher behaviours. The Statgraphics
      statistical package aided the production of descriptive statistics, and also
      validation of the internal construct of the behaviour categories. Results showed
      that the majority of students were dissatisfied with the amount of link teacher
      contact they receive. A minimum length of time for each visit was established.
      The link teacher behaviours found to be most helpful were related to
      interpersonal skills and personality followed by nursing competence, evaluation
      and teaching ability. The findings contribute to the literature addressing UK
      students' views, and will inform the development of a higher quality link teacher
      support system for senior student nurses.

PMID- 9277166
TI  - Project 2000 student nurses' creative approach to peer education.
AB  - This research paper gives an account of an unique initiative using interactive
      drama with Project 2000 student nurses, to facilitate health promotion with
      pupils at secondary school level. Through an open-ended play lasting 12 minutes
      (entitled Debbie) and workshops, student nurses communicated sexual health
      promotion and how to make choices to a group of 14-18 year olds in a large
      comprehensive school. The initiative, which uses participant action research
      (Altricher 1993), was designed to assess whether student nurses could effectively
      communicate health promotion to pupils with whom they were comparable in age, and
      the educative effects on the students as a result of engaging in the initiative.
      It was clear from the findings that several student nurses were unprepared for
      the impact that the initiative would have on them. The play had immense power and
      they had empathy with the pupils. Perceived personal and professional benefits
      gained by the students (as reported by them) included a sense of belonging, more
      independence, more openness, less inhibition, increased knowledge, improved
      communication skills, confidence, assertiveness, self-esteem, and the ability to
      educate people. The author argues that a creative approach to teaching the
      theoretical underpinning of health promotion alongside practical dramatic skills
      of communication to empower, as well as promote change, can enable effective
      facilitation amongst young people.

PMID- 9277167
TI  - Of tombstones, milestones, and gemstones: a retrospective and prospective on
      nursing theory, c. 1997.

PMID- 9277168
TI  - Beyond a decade of research: moving to the white hole of unitary science.

PMID- 9277170
TI  - What is nursing science? An international dialogue.

PMID- 9277169
TI  - Retrospective and prospective of practice applications: views in the fog.

PMID- 9277171
TI  - Reflections on the past and a vision for the future.

PMID- 9277172
TI  - The Neuman systems model: reflections and projections.

PMID- 9277173
TI  - Evolution of the theory of health as expanding consciousness.

PMID- 9277174
TI  - Views of human beings specific to nursing.

PMID- 9277175
TI  - The Human Becoming theory: the was, is, and will be.

PMID- 9277176
TI  - Martha E. Rogers: an icon of nursing.

PMID- 9277177
TI  - Future of the Roy model: challenge to redefine adaptation.

PMID- 9277178
TI  - The theory of Human Caring: retrospective and prospective.

PMID- 9277179
TI  - The Roy Adaptation model and patient/family experiences.

PMID- 9277180
TI  - Nursing guided by Parse's theory: patient views at Sunnybrook.

PMID- 9277182
TI  - The need to find an alternative model of health care.

PMID- 9277181
TI  - Practice guided by Watson's theory: the Denver Nursing Project in Human Caring.

PMID- 9277183
TI  - Nurse activism could stop AIDS pandemic.

PMID- 9277184
TI  - Children in need.

PMID- 9277185
TI  - Teaming up for the future.

PMID- 9277186
TI  - Zombies in the night.

PMID- 9277188
TI  - International focus: when tomorrow comes.

PMID- 9277187
TI  - Peace is just the beginning.

PMID- 9277189
TI  - International focus: feeling the buzz. Interview by Ian McMillan.

PMID- 9277191
TI  - International focus: at the barricades.

PMID- 9277190
TI  - International focus: it doesn't add up.

PMID- 9277192
TI  - Developing practice through networking.
AB  - Exhorted to provide evidence-based practice, be accountable practitioners,
      provide a value for money service and to expand the nursing role, nurses can be
      forgiven for wondering just how they can meet these laudable targets while coping
      with all the other stresses that are part and parcel of life in today's NHS This
      article reports on a network which offers appropriate support.

PMID- 9277193
TI  - Promoting action research in healthcare settings.
AB  - To coincide with the first annual Action Research conference taking place in
      London this week, this article promotes the idea of using action research for
      health care exploration and change. It also introduces the work of the Healthcare
      Subgroup of the Collaborative Action Research Network, the group's aims and how
      practitioners can make contact and be involved with the development. The article
      also describes the outcomes of a research study that underpin the philosophy,
      process and potential benefits of the network as a means to promote practice
      development and change in client care.

PMID- 9277194
TI  - Principles of consent: issues for the radiology nurse.
AB  - This article considers the law relating to consent to treatment, raised by
      delegates at an RCN forum for radiology and cardiology nurses. The author
      outlines general principles of consent to treatment which apply to all
      specialties, and discusses the specific issues raised by nurses' questions about
      consent for radiological investigations.

PMID- 9277195
TI  - Improving hospital discharge arrangements for older people.

PMID- 9277196
TI  - Assessment and care for people with dementia.

PMID- 9277197
TI  - Call for mandatory HIV accident rules.

PMID- 9277198
TI  - Stakeholding on the menu.

PMID- 9277199
TI  - Caught in the act.

PMID- 9277200
TI  - Diary of a festival.

PMID- 9277201
TI  - Labour in office--shotgun weddings.

PMID- 9277202
TI  - A question of urgency.

PMID- 9277203
TI  - The future is in your hands.

PMID- 9277204
TI  - Step up the pressure.

PMID- 9277205
TI  - A kick up the ballot.

PMID- 9277206
TI  - Failing the screen test.

PMID- 9277208
TI  - Environment--pedal power.

PMID- 9277209
TI  - Studying abroad--travel light.

PMID- 9277207
TI  - Know how--diabetic foot ulceration.
AB  - Diabetes is a complex metabolic disease which can give rise to many tissue
      complications. The foot is particularly vulnerable to circulatory and
      neurological disorders, so that even minor trauma can lead to ulceration and
      infection. Careful observation and assessment of these wounds is essential to
      ensure the integrity of the limb is not threatened, which could result in
      amputation. A multidisciplinary team approach is the key to successful management
      of diabetic foot ulceration.

PMID- 9277210
TI  - The search for the key to Alzheimer's.

PMID- 9277211
TI  - The market leader.

PMID- 9277212
TI  - Nurse practitioner service relieves pressure in A&E.

PMID- 9277213
TI  - Shared care recording in community care.
AB  - This article details the results of a pilot study of shared care recording
      between elderly people with multiple needs who live at home and their care
      helpers and providers.

PMID- 9277215
TI  - Nurses prescribing wound dressings.

PMID- 9277214
TI  - Drug-related problems in older people.
AB  - This is the second of two articles looking at medication problems in older
      people. Here, the prevention and management of drug-related problems is discussed
      and a case study presented illustrating a problem in practice. The first article
      was published on July 2.

PMID- 9277217
TI  - The world is your oyster.

PMID- 9277216
TI  - Eating disorders--the role of the nurse.
AB  - The role of the nurse in the treatment of eating disorders requires a wide range
      of skills and confidence in managing high levels of anxiety. For many patients,
      the nurse is the key professional involved in their care and is in a position to
      offer significant treatment and support to individuals who suffer these
      distressing problems.

PMID- 9277218
TI  - From high-rise anxieties to the valleys of despair.

PMID- 9277219
TI  - French connection.

PMID- 9277220
TI  - A health care revolution.

PMID- 9277221
TI  - Home comforts on display.

PMID- 9277222
TI  - DIY (do it yourself) injections guaranteed to blow your mind.

PMID- 9277223
TI  - Sum like it not.

PMID- 9277224
TI  - High pressure areas.
AB  - The study highlighted the extent of occupational distress in a group of nurses in
      an NHS hospital trust. The levels of distress were similar across settings and
      similar to levels identified in current NHS-wide studies. Levels of work pressure
      and emotional exhaustion were higher than previous UK norms. High levels of
      distress were associated with younger age, high work pressure and low social
      support. For general mental well-being individual factors, such as satisfaction
      with social support, were more predictive than organisational factors. For work
      specific distress, factors in the work environment, such as work pressure,
      patient contact and task orientation, were more important. Strategies for
      addressing the needs identified were reviewed and are now being implemented.

PMID- 9277225
TI  - Stretched to breaking point.

PMID- 9277226
TI  - Coping with stress.

PMID- 9277227
TI  - Nursing abroad--a world apart.

PMID- 9277228
TI  - Nursing abroad--after the battle.

PMID- 9277229
TI  - Older people--link up, check up, speak up.

PMID- 9277230
TI  - Mental health--fear and loathing.

PMID- 9277231
TI  - Childbirth--the stranger and I.

PMID- 9277232
TI  - Hypodermoclysis as a means of rehydration.
AB  - This article discusses the use of hypodermoclysis, a method of fluid replacement
      that is little practised by today's physicians and nurses, although it was widely
      used in the early 1950s. The article reviews the literature on the use of
      hypodermoclysis as a safe and convenient method of fluid administration, and
      spotlights some concerns surrounding the use of hypodermoclysis.

PMID- 9277233
TI  - Life and death decisions about babies' treatment.
AB  - Withdrawing and withholding treatment is an emotive issue, especially when it
      relates to babies. This paper describes a study exploring the perceptions of
      doctors, nurses and midwives involved in such decisions. It found that nurses and
      midwives were reluctant to express their opinions. This resulted in practices and
      decisions with which they were not always in total agreement. Recommendations
      have been made for better preparation in ethical reasoning, improved
      communication and team effort.

PMID- 9277234
TI  - How a primary care specialist role for HIV/AIDS was set up.

PMID- 9277235
TI  - In search of therapeutic nursing: maxi-nurses.
AB  - The third article in this series examines two nurse-led units where access to the
      service is controlled by nurses. However, in many ways they could not be more
      different. The special care unit in the USA provides rehabilitative care for
      patients discharged from intensive care, while the nursing centre in Canada
      offers a drop-in service offering advice to local people.

PMID- 9277236
TI  - Eating disorders. Professional issues.

PMID- 9277237
TI  - Auditing infection.

PMID- 9277238
TI  - Infection control: a little knowledge is a dangerous thing.

PMID- 9277240
TI  - Can primary care physicians be a resource to their patients in decisions
      regarding alternative and complementary therapies for cancer?

PMID- 9277239
TI  - Infection control: prevention better than cure.

PMID- 9277241
TI  - The discursive formation of health. A study of printed health education material
      used in primary care.
AB  - This study analyses printed educational material on cholesterol, food and health
      related lifestyle changes used in primary care in southern Sweden. Two
      theoretically grounded perspectives are used: orientation of knowledge and
      rhetoric. According to the first one, the material contained many examples of
      abstract and detailed knowledge, such as tables of energy contents, and a little
      less of action-oriented and detailed knowledge, such as food recipes. We also
      found a few examples of comprehensive, abstract knowledge, such as theoretic
      explanations. Action-oriented and comprehensive knowledge, relating health to
      lifestyle, were rare. The rhetoric style of the material was generally dominated
      by plain facts, without any identified voice (i.e. sender) or any emotional
      orientation. Overall, information was not related to 'the voice of the life
      world' but to 'the voice of medicine', and it was in character more general than
      specific.

PMID- 9277242
TI  - Helping smokers make decisions: the enhancement of brief intervention for general
      medical practice.
AB  - Primary care clinicians are often encouraged by government agencies to intervene
      systematically with all smokers. Pressure of time and pessimism about their own
      efficacy and patients' capacity to change are some of the reasons why clinicians
      do not feel it is appropriate to always advise every patient about unhealthy
      behaviours. Developments in patient centred approaches to the consultation and
      progress in the addictions field suggest that new consulting methods could be
      constructed which are more satisfying than giving brief advice to change. The aim
      of this study was to develop a structured, teachable and acceptable intervention
      for clinicians to help patients consider their smoking during general medical
      consultations. Patient centred strategies derived from the stages of change model
      and motivational interviewing and its adaptations were explored in experimental
      consultations with 20 volunteer smokers. Feedback from them and from general
      practice registrars trained in the use of the method informed its development.
      Acceptability to clinicians was assessed by semi structured telephone interviews
      with 24 general practice registrars who participated in a randomised controlled
      trial assessing the effectiveness of the method. Anonymous, written
      questionnaires were also completed by 20 of the registrars who recruited ten or
      more patients into the trial. The method is described. Key components are:
      establishing rapport, assessing motivation and confidence, and then depending on
      the response, asking standard scaling questions, asking about pros and cons of
      smoking, non-judgmental information sharing, brainstorming solutions and
      negotiating attainable goals and follow-up. The clinicians used the method with a
      total of 270 smokers, taking an average of 9.69 min with each patient. Evaluation
      reveals that it is acceptable to the group of general practice registrars. Longer
      consultation time was seen as the main drawback. We conclude that acceptable
      methods for opportunistic health promotion can be developed by taking into
      account patient centred approaches to the consultation, developments from the
      addictions field and the practical problems faced by clinicians. The process can
      be further enhanced by considering feedback from those who are likely to receive
      and use the interventions.

PMID- 9277243
TI  - Methodologies for informing beneficiaries of their rights: evaluating the
      Important Message from Medicare.
AB  - The Important Message from Medicare, a letter given to US Medicare patients upon
      hospital admission, was originally designed to allay the concerns of the Health
      Care Financing Administration (HCFA), Peer Review Organizations (PROs), and the
      beneficiary community that patients did not know their rights under Medicare and
      the PRO program. The effectiveness of the current Message may be adversely
      affected by the complexity of its language, the multifaceted admissions process,
      priorities of sick patients, and the demand for hospital resources. This study
      evaluated the effectiveness of the Message and various alternatives for informing
      beneficiaries of their rights. With HCFA financing, PROs in 10 states surveyed
      random samples of Medicare beneficiaries to measure knowledge of their rights
      under the current system and after the implementation of alternatives. This study
      found that there are alternative ways of informing Medicare beneficiaries of
      their rights which are more effective than the current Important Message from
      Medicare.

PMID- 9277244
TI  - Physician responses to an educational intervention on improving their long-term
      prescribing of sedatives.
AB  - The current study examined response forms returned by physicians in response to a
      Medicaid retrospective therapeutic intervention on the long-term use of
      sedatives. The educational intervention was designed to notify physicians about
      their patients' long-term use of sedatives and suggest that they reevaluate the
      patient's need for sedative hypnotic medication and decrease or discontinue
      prescribing the medication and/or suggest non-pharmacological alternatives if
      deemed appropriate. Forty-seven percent of physicians responded to the
      educational intervention. Nineteen percent of responding physicians planned to
      change the patient's medication in some way. The most common planned change was
      to decrease the dose. Physicians also stated that they would recommend one or
      more non-pharmacological alternatives to 17% of patients. Thirty-eight percent of
      physicians planned to monitor and/or counsel the patient. Over 40% of physicians
      reported planning no action after receiving the intervention. Twenty-six percent
      of physicians planned no action because of patient demand for the sedatives. The
      study concludes that physicians need to be better trained on how to: (1) discuss
      non-pharmacological treatments with patients and (2) deal with and respond to
      patients who demand controlled substances.

PMID- 9277245
TI  - Continuity of information in cancer care: evaluation of a logbook.
AB  - A logbook, or patient-dossier, was developed, to improve continuity of
      information in the treatment and care of head-and-neck cancer patients. It
      contained information modules on different aspects of care, as well as forms to
      facilitate communication both between patient and care-professional and between
      the various care-professionals. The logbook's effectiveness was evaluated in two
      hospitals in Rotterdam, by comparing outcomes for trial and comparison groups of,
      respectively, 71 and 54 patients and 59 and 35 care-professionals. Trial patients
      proved to be better informed, to receive more support and to experience fewer
      psychosocial problems. Professionals who used the logbook were better informed
      about their patients, and about the care-activities of fellow-professionals than
      those who did not. They recognised an improvement in their contact with
      colleagues and in the harmonisation of their respective care-activities.

PMID- 9277246
TI  - Accidents among high school pupils in Israel: a recurrent disease?
AB  - Accidents are unexpected events usually producing injury. Many victims of trauma
      have a history of recurrent accidents. This study is a preliminary effort to
      verify the hypothesis that accidents may be considered as a recurrent disease in
      certain families; these children and families belong to a 'high risk group'. Two
      hundred seventy-nine high school pupils participated in the study. Every pupil
      had experienced 1.7(+/- 1.7) mild to serious injuries that necessitated medical
      treatment during the years of elementary and high school. The geographical
      location of accidents was as follows: 26.4% were on the road; 23.1% occurred at
      school; 28.6% were associated with sport activities; and 22% occurred at home.
      The prevalence of injuries among boys was higher than among girls. A correlation
      was found between the number of accidents of the pupils and those of close family
      members, suggesting that these children and families are prone to accidents and
      form a 'high risk group'. The knowledge of accident and injury prevention did not
      change significantly during high school studies. The principal source of
      knowledge of accident and injury prevention of the pupils were the media: TV
      (98.8%), newspapers: (65.6%), and radio (58.1%). The contribution of physicians
      and nurses to this knowledge was very slight (16.5%). These families should be a
      target population; an educational program should be organized and transmitted by
      the media; family meetings with educational advisors, physicians and nurses
      should take place at school, especially for these target families. As a
      preventive measure for all, and especially to the high risk group, we would
      suggest that high school pupils work for 1-3 months in rehabilitation centers in
      which they can see the consequences of accidents and thereby gain an
      understanding of the effects of injury on the patient and his family.

PMID- 9277247
TI  - Design, development, and evaluation of visual aids for communicating prescription
      drug instructions to nonliterate patients in rural Cameroon.
AB  - In this study, culturally sensitive visual aids designed to help convey drug
      information to nonliterate female adults who had a prescription for a solid oral
      dosage form of antibiotic medications were developed and evaluated. The
      researchers conceptualized the educational messages while a local artist produced
      the visual aids. Seventy-eight female ambulatory patients were evaluated for
      comprehension and compliance with antibiotic prescription instructions. The study
      was conducted in three health centers in Cameroon, West Africa and followed a pre
      test, post-test, and follow-up format for three groups: two experimental, and one
      control. All participants were randomly assigned to either experimental or
      control groups, 26 patients to each group. Subjects in the experimental groups
      received visual aids alone or visual aids plus an Advanced Organizer. A
      comparison of the three groups showed that subjects in the experimental groups
      scored significantly higher than the control group in both the comprehension and
      compliance measures.

PMID- 9277248
TI  - [Dying in dignity].

PMID- 9277249
TI  - [The service enterprise "Hospital" is an important socioeconomic factor].

PMID- 9277250
TI  - [Cooperation between humans and technology is necessary. Old age homes can save
      25% of personnel by use of apparatus].

PMID- 9277251
TI  - [In case of a law suit, documentation will be meticulously searched for errors].

PMID- 9277252
TI  - [Cold shower and hay flower. Sebastian Kneipp died 100 years ago].

PMID- 9277253
TI  - [Modern methods of wound treatment. 2. For every wound there is the proper
      dressing].

PMID- 9277254
TI  - [Transcutaneous electric nerve stimulation: a therapy that promises help in
      chronic pain].

PMID- 9277255
TI  - [Nursing grand rounds in intensive care. The patient is the center].

PMID- 9277256
TI  - [Nursing standards and methods of treatment in dermatology. 1. Pathological skin
      reactions may be signs of systemic disease].

PMID- 9277257
TI  - [Health care delivery and nursing in Uganda: lacking connections, only money will
      help].

PMID- 9277258
TI  - [Who is studying nursing management at the vocational school in Munster? First
      results of scientific mentoring].

PMID- 9277259
TI  - [A comparative analytic, study of need-oriented nursing models].

PMID- 9277260
TI  - Changing practices in the weaning of babies in Britain.

PMID- 9277261
TI  - Changing working practice. Setting up a Saturday morning child health clinic.

PMID- 9277262
TI  - Support for mothers from charity and industry. 'Eating for Pregnancy' helpline.

PMID- 9277263
TI  - The prevention and treatment of nappy rash. Some fresh insights into an old
      problem.

PMID- 9277264
TI  - A practice nurse's life can be a happy one.

PMID- 9277265
TI  - Special diets. What is a gluten-free diet and why is it needed?

PMID- 9277266
TI  - Understanding grief. Grief and the concept of loss in midwifery practice. Part 2.
      Grief in obstetrics and midwifery.

PMID- 9277267
TI  - Summer holiday advice. Sunburn--don't do it!

PMID- 9277268
TI  - Federal court upholds NY ban on direct-entry midwives.

PMID- 9277269
TI  - O.R. nurse testifies as "expert" re negligence of O.R. tech. Case on point:
      Healthtrust, Inc. v. Cantrell 689 So. 2d 822--AL (1997).

PMID- 9277270
TI  - LA: aged pt. falls from bed--$555,000 verdict: suit brought against hospital, Dr.
      & nurse. NJ: lap pad left in patient--$500,000 verdict: negligence allocated
      between Dr., Tech & R.N.

PMID- 9277271
TI  - By whom is an "Agency" nurse employed? Case on point: Hansen v. Caring
      Professionals, Inc. 676 N.E. 2d 1349--IL (1997).

PMID- 9277272
TI  - Are "Captain of Ship" & "Borrowed Servant" doctrines alive & well?

PMID- 9277273
TI  - Nurse is victim of malpractice: contributory negligence. Case on point: Prabhu v.
      Levine 930 P. 2d 103--NV (1996).

PMID- 9277274
TI  - NY: aide found guilty of patient abuse: court lifts ban on future employment. LA:
      nurse administers injection improperly: nurse-patient knew of error--limitations
      issue.

PMID- 9277275
TI  - Applicant found cheating on NCLEX: board denies licensure. Case on point:
      Culpepper v. State 930 P. 2d 508--AZ (1996).

PMID- 9277276
TI  - [Health education: some considerations and implications for nursing practice].
AB  - The article focuses on distincts approaches on Health Education, analyzing its
      implications for the nursing practice in the health work process. It emphasizes
      the importance of this theme for the health agents' education for a
      interdisciplinary work with social sciences. It also points out some implications
      of the social citizenship's developing approach for nursing practice and
      education.

PMID- 9277277
TI  - [Family relations and gender identity: a contribution to the care of expanding
      families].
AB  - It approaches the influences of family relationship in the construction of the
      gender identity process, through the Theory of Objectal Relationship referential,
      proposed by Chorodow (1979). This theoretical support, emphasizes that the gender
      identity is basically influenced by the primary bonds established between child
      and adults, through the continuous personal relationship developing mother and
      father role. It points out that the gender construction for the boy and for the
      girl happens in a different way. It concludes pointing out some lines to be
      adopted by the nurse in the practice with families, as well as, some limitation
      of the Theory of Objectal Relationship.

PMID- 9277278
TI  - [The phenomenological method in psychiatric nursing research].
AB  - The author approaches some ideas about phenomenology, general lines of
      phenomenological research and some considerations about phenomenology and
      psychiatric nursing, as an attempt to allow a profounder view of these themes. He
      makes a reflection about this area of work, descrying possibilities for caring
      the human being with psychiatric suffering, based on the comprehension of this
      individual.

PMID- 9277279
TI  - [Analysis of shift changes in the nursing unit of the Radiology Department of the
      Hospital de Clinicas in Porto Allegre].
AB  - The author evaluates shift changes on the Nursing Unit in the Radiology
      Department of Hospital de Clinicas de Porto Alegre which were established two
      years ago. She emphasizes the importance of communication among members of the
      team and presents the results of an observation done by auxiliary personnel
      during shift changes.

PMID- 9277280
TI  - [Evaluating the performance appraisal in daily nursing practice].
AB  - The objective of this study was determine the development of performance
      appraisal in daily nursing practice aiming to up-date and adequate the program of
      Nursing Management Post-graduation Courses. The sample was composed by 27 nurses
      students of the first and second post-graduation course in 1994 and 1995. The
      results showed that performance appraisal is not established in the nurses work
      reality (51%) and 70% of respondents assert that they did not receive any
      training in this field. The qualitative results added to quantitative data allow
      to point the necessity to invest in nursing education both in graduation and post
      graduation levels, to carry out the performance appraisal like a process
      searching the development and improvement of human resources and working
      relations.

PMID- 9277281
TI  - [Knowledge about AIDS prevention among professionals and students in health
      care].
AB  - This work is a exploratory research based on the analysis of the answers to the
      questionnaires of 52 students and health care professionals knowledge about AIDS
      sexual prevention, biosecurity, diagnosis tests, patients and workers rights and
      the modifications of nursing and medical care to this kind of disease.

PMID- 9277282
TI  - [Resistance of intensive care unit nurses to caring for conscious patients].
AB  - The authors believe that intensive Care Units (ICU) is a very stressful place for
      both patients and workers. They associate the success of the treatment to the
      relationship between these two groups. This article intends to investigate the
      existence of resistance among nursing personnel in assisting conscious patient in
      ICU. The date were analyzed through the "content analysis" proposed by Bardin
      (1979) and through the methodology utilized by Magaihaes (1991).

PMID- 9277283
TI  - Cold hearts & soft heads in the healthcare industry.

PMID- 9277284
TI  - Suburban hospital nurses fight for safe staffing.

PMID- 9277286
TI  - Total quality management--an update.

PMID- 9277285
TI  - The legal consequences of practicing beneath your licensure status.

PMID- 9277287
TI  - Interview with Suzanne Gordon on life support.

PMID- 9277288
TI  - Merger mania and philanthropy in health care.

PMID- 9277289
TI  - Managed care's scorched--earth medical and hospital policy.

PMID- 9277290
TI  - The golden age for health care.

PMID- 9277291
TI  - Managed healthcare is a crime against humanity.

PMID- 9277292
TI  - When the nurse becomes the patient.

PMID- 9277293
TI  - Building bridges.

PMID- 9277294
TI  - Baltimore hospital bucks RN staff reduction trend.

PMID- 9277295
TI  - Caring for the healthy: taking wellness to a new dimension.

PMID- 9277296
TI  - I can make a difference-sometimes.

PMID- 9277297
TI  - Legal update. Cases from the court.

PMID- 9277298
TI  - Considerations before signing an organ donor card.

PMID- 9277299
TI  - H.R. 4315 in the House of Representatives.

PMID- 9277300
TI  - Opportunities galore! How to set goals and achieve them.

PMID- 9277301
TI  - Is entrepreneurship a good choice for you?

PMID- 9277302
TI  - The personality of a successful guerilla.

PMID- 9277303
TI  - Cost-cutters eliminate skilled nurses.

PMID- 9277304
TI  - Three Denver nurses may face prison in a case that bodes ill for the profession.

PMID- 9277305
TI  - Kaiser Permanente strike.

PMID- 9277307
TI  - Caught between the cross fire.

PMID- 9277306
TI  - A license to care.

PMID- 9277308
TI  - Shame and gossip within the workplace.

PMID- 9277309
TI  - Nurses make the difference!

PMID- 9277310
TI  - Staff nurses vs nurse managers--no winners here.

PMID- 9277311
TI  - Empowerment as a source of healing: redefining the art of nursing management.
AB  - Empowerment amounts to a social process of recognizing, promoting and enhancing
      staff nurse abilities to meet self needs, solve their own problems and mobilize
      the necessary resources to gain mastery over their own professional lives.
      Healing, to be made whole, is a process of getting in touch with that which is
      impeding our realization of wholeness. Empowerment as a source of organizational
      healing conveys the message that in order to realize wholeness, nurses are
      dependent upon personal and organizational resources. As nurses learn multiple
      ways to interact with the work environment, they find the path to a wholeness
      that incorporates physical, emotional, intellectual, and spiritual aspects of
      themselves. As the value of wholeness is realized individually, interactions with
      the environment spontaneously manifest these attributes and the message permeates
      the nursing community. As the nursing community is empowered, it is increasingly
      able to empower the individual. This expanding energy can result in a synergistic
      pattern that brings phenomena together, and interrelates them, creating a new and
      greater whole from the disparate, seemingly conflicting parts. When nurses as
      individuals and groups are able and willing (empowered) to invest energy to that
      which impacts their lives so that they can move toward wholeness (heal), positive
      energy exponentially intensifies and permeates the environment to envelop all.

PMID- 9277312
TI  - Caring: a political platform.
AB  - It must be remembered that a vision exists and there are means to accomplish this
      vision. We have identified dialogue, collaboration, building of relationships,
      unity, activism, and research as the key ingredients that need to be fostered.
      The challenge is here. Caring is being legislated. It is up to all of us, nurses
      and consumers alike, to retain caring as a health factor. For nurses, what better
      way to express our capacity than in accepting the torch of political activism. It
      is our turn!

PMID- 9277313
TI  - Creating healthy work: stress in the nursing workplace.

PMID- 9277314
TI  - Nursing and the law--retaliatory termination.

PMID- 9277315
TI  - How do you stand it?

PMID- 9277316
TI  - Ageism, healthcare, and older women.

PMID- 9277317
TI  - Staff nurse perceptions of health care system changes & nursing management models
      on client outcomes.
AB  - This investigation reports the results of a national survey of staff nurse
      perceptions of changes in the health care system and nursing management models on
      client outcomes.

PMID- 9277319
TI  - Winning profits with guerrilla marketing.

PMID- 9277318
TI  - Make it happen--starting your own supportive care agency.

PMID- 9277320
TI  - [Casts and music in children].

PMID- 9277321
TI  - [Are artists patients like everyone else?].

PMID- 9277322
TI  - [Care planning on the wall].

PMID- 9277323
TI  - [Stoma therapy. Quality of life and quality of care].

PMID- 9277324
TI  - [Did you say stoma therapist?].

PMID- 9277325
TI  - [Digestive tract stomata: why and where?].

PMID- 9277326
TI  - [The clinical certificate in stoma therapy].

PMID- 9277327
TI  - [A stoma for life. Interview by Ghislaine Trabacchi ].

PMID- 9277328
TI  - [Complications of intestinal stomas].

PMID- 9277329
TI  - [The nurses' pain].

PMID- 9277330
TI  - [What health policy to chose in favor of the dependent aged?].

PMID- 9277331
TI  - [Nutrition and health: what is the relationship?].

PMID- 9277332
TI  - [Toxoplasmosis: cats, nutrition ... a risk in pregnancy].

PMID- 9277333
TI  - Myosin I.
AB  - The class I myosins are single-headed, actin-binding, mechanochemical "motor"
      proteins with heavy chains in the molecular mass range of 110-130 kDa; they do
      not form filaments. Each myosin I heavy chain is associated with one to six light
      chains that bind to specific motifs known as IQ domains. In vertebrate myosin I
      isoforms, the light chain is calmodulin, which is thought to regulate motor
      activity. Proteins similar to calmodulin are associated with myosin I isoforms
      from lower eukaryotes. Some myosin I isoforms from lower eukaryotes are regulated
      by phosphorylation; however, the phosphorylation site is not present in
      vertebrate myosin I isoforms. Based on sequence analyses of the amino terminal
      "head" domains, myosin I can be subdivided into several subclasses. Analyses of
      the biochemical properties of the isolated molecules and localization studies
      support the proposal of roles for these molecules in intracellular trafficking
      and changes in membrane structure. Our present understanding of the properties of
      these molecules and their proposed roles is reviewed here.

PMID- 9277334
TI  - Role of concentration and size of intracellular macromolecules in cell volume
      regulation.
AB  - To gain insight into the mechanism(s) by which cells sense volume changes,
      specific predictions of the macromolecular crowding theory (A. P. Minton. In:
      Cellular and Molecular Physiology of Cell Volume Regulation, edited by K.
      Strange. Boca Raton, FL: CRC, 1994, p. 181-190. A. P. Minton, C. C. Colclasure,
      and J. C. Parker. Proc. Natl. Acad. Sci. USA 89: 10504-10506, 1992) were tested
      on the volume of internally perfused barnacle muscle cells. This preparation was
      chosen because it allows assessment of the effect on cell volume of changes in
      the intracellular macromolecular concentration and size while maintaining
      constant the ionic strength, membrane stretch, and osmolality. The predictions
      tested were that isotonic replacement of large macromolecules by smaller ones
      should induce volume decreases proportional to the initial macromolecular
      concentration and size as well as to the magnitude of the concentration
      reduction. The experimental results were consistent with these predictions:
      isotonic replacement of proteins or polymers with sucrose induced volume
      reductions, but this effect was only observed when the replacement was > or = 25%
      and the particular macromolecule had an average molecular mass of < or = 20 kDa
      and a concentration of at least 18 mg/ml. Volume reduction was effected by a
      mechanism identical with that of hypotonicity-induced regulatory volume decrease,
      namely, activation of verapamil-sensitive Ca2+ channels.

PMID- 9277335
TI  - Coordinated expression of myosin heavy chain isoforms and metabolic enzymes
      within overloaded rat muscle fibers.
AB  - We studied the coordinated regulation of myosin heavy chains (MHC) and metabolic
      enzymes within individual overloaded adult rat plantaris fibers. This was done
      using monoclonal antibodies raised against distinct developmental and adult MHCs,
      and quantitative microphotometric succinate dehydrogenase (SDH) and glycerol-3
      phosphate dehydrogenase (GPDH) enzyme assays. Overload shifted MHC expression in
      the order IIb-->IIx-->IIa-->alpha/I, with a tripling of cells coexpressing I and
      alpha-MHC, and a transient reexpression of two embryonic MHC and the neonatal
      isoform in preexisting myofibers. Overload caused a rapid, size-independent, 50%
      decrease in GPDH activity across all cell types, which recovered by 6 wk. Fiber
      SDH activities varied according to MHC composition, such that overloaded fibers
      coexpressing IIa MHC displayed control slow fiber SDH levels, whereas cells
      expressing IIx and IIb MHC displayed a transient 30% increase in SDH that
      recovered by 6 wk. Our results suggest that during overload, fibers adapt
      progressively to the new functional requirements and display more efficient
      cellular energy utilization and delivery characteristics. The time course of
      adaptations suggests a role for glycolytic enzymes in the initiation of these
      transformations.

PMID- 9277336
TI  - Characterization of the human pH- and PKA-activated ClC-2G(2 alpha) Cl- channel.
AB  - A ClC-2G(2 alpha) Cl- channel was identified to be present in human lung and
      stomach, and a partial cDNA for this Cl- channel was cloned from a human fetal
      lung library. A full-length expressible human ClC-2G(2 alpha) cDNA was
      constructed by ligation of mutagenized expressible rabbit ClC-2G(2 alpha) cDNA
      with the human lung ClC-2G(2 alpha) cDNA, expressed in oocytes, and characterized
      at the single-channel level. Adenosine 3',5'-cyclic monophosphate-dependent
      protein kinase (PKA) treatment increased the probability of opening of the
      channel (Po). After PKA activation, the channel exhibited a linear (r = 0.99)
      current-voltage curve with a slope conductance of 22.1 +/- 0.8 pS in symmetric
      800 mM tetraethylammonium chloride (TEACl; pH 7.4). Under fivefold gradient
      conditions of TEACl, a reversal potential of +21.5 +/- 2.8 mV was measured
      demonstrating anion-to-cation discrimination. As previously demonstrated for the
      rabbit ClC-2G(2 alpha) Cl- channel, the human analog, hClC-2G(2 alpha), was
      active at pH 7.4 as well as when the pH of the extracellular face of the channel
      (trans side of the bilayer; pHtrans) was asymmetrically reduced to pH 3.0. The
      extent of PKA activation was dependent on pHtrans. With PKA treatment, Po
      increased fourfold with a pHtrans of 7.4 and eightfold with a pHtrans of 3.0.
      Effects of sequential PKA addition followed by pHtrans reduction on the same
      channel suggested that the PKA- and pH-dependent increases in channel Po were
      separable and cumulative. Northern analysis showed ClC-2G(2 alpha) mRNA to be
      present in human adult and fetal lung and adult stomach, and quantitative reverse
      transcriptase-polymerase chain reaction showed this channel to be present in the
      adult human lung and stomach at about one-half the level found in fetal lung. The
      findings of the present study suggest that the ClC-2G(2 alpha) Cl- channel may
      play an important role in Cl- transport in the fetal and adult human lung.

PMID- 9277337
TI  - Myosin heavy chain gene expression in neonatal rat heart cells: effects of
      [Ca2+]i and contractile activity.
AB  - To determine if mechanical signals or alterations in intracellular Ca2+
      concentration ([Ca2+]i) affect myosin heavy chain (MHC) gene expression in
      spontaneously beating, neonatal rat ventricular myocytes, contractile activity
      was inhibited with verapamil, KCl, or 2,3-butanedione monoxime (BDM), and their
      acute and chronic effects on myocyte shortening, [Ca2+]i, and MHC gene expression
      were examined. Despite their differing effects on [Ca2+]i, verapamil, KCl, and
      BDM all inhibited contractile activity and markedly downregulated beta-MHC mRNA
      levels to 24 +/- 5, 21 +/- 7, and 6 +/- 2% of contracting cells, respectively. In
      contrast, these inhibitors of contraction upregulated alpha-MHC mRNA levels to
      163 +/- 19, 156 +/- 7, and 198 +/- 20% of contracting cells, respectively.
      Transient transfection with a rat beta-MHC promoter-luciferase expression plasmid
      demonstrated that all inhibitors of contraction significantly decreased beta-MHC
      promoter activity. Paradoxically, contractile arrest also inhibited alpha-MHC
      promoter activity, suggesting that increased alpha-MHC mRNA levels resulted from
      posttranscriptional mechanisms. Actinomycin D mRNA stability assays indicated
      that alpha-MHC mRNA half-life was prolonged in noncontracting cells (33 h)
      compared with contracting myocytes (14 h). Contraction-dependent alterations in
      MHC gene expression were not dependent on release of angiotensin II or other
      growth factors into the culture medium. Thus intrinsic mechanical signals rather
      than alterations in [Ca2+]i regulate alpha-MHC and beta-MHC gene expression by
      both transcriptional and posttranscriptional mechanisms.

PMID- 9277338
TI  - Control of cytosolic pH in two-cell mouse embryos: roles of H(+)-lactate
      cotransport and Na+/H+ exchange.
AB  - In this study we used imaging techniques with the fluorescent pH-sensitive dye
      2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein to investigate the control of
      cytosolic pH (pHi) in two-cell mouse embryos in nominally HCO3(-)-free
      conditions. We found that the resting pHi of two-cell embryos (40-50 h after
      human chorionic gonadotropin) in HCO3(-)-free M2 was 7.31 +/- 0.01 (n = 172
      embryos), which is significantly above the level predicted if H+ is at
      electrochemical equilibrium. We showed that two-cell embryos contain a H(+)
      monocarboxylate cotransport system with apparent Michaelis constants for D
      lactate, L-lactate, and pyruvate of 11.5, 3.7, and 3.5 mM, respectively. It is
      inhibited by p-chloromercuribenzoic acid (300 microM), p
      chloromercuriphenylsulfonic acid (300 microM), and alpha-cyano-4-hydroxycinnamate
      (1 mM) and is insensitive to 4,4'-diisothiocyanodihydrostilbene-2,2'-disulfonic
      acid (500 microM). We also showed that the pHi response to the acid load produced
      by an NH4Cl pulse has two components, one due to H(+)-monocarboxylate cotransport
      and the other due to Na+/H+ exchange. We found no evidence that a H+ conductance
      was responsible in these cells for the recovery in pHi after an acid load.

PMID- 9277339
TI  - Sarco(endo)plasmic reticulum Ca2+ pump isoform SERCA3 is more resistant than
      SERCA2b to peroxide.
AB  - Sarco(endo)plasmic reticulum Ca2+ pumps are encoded by genes SERCA1, SERCA2, and
      SERCA3. Most tissues express SERCA2 Ca2+ pumps (splice SERCA2b) which are
      inactivated by reactive oxygen. In contrast, SERCA3 is expressed in tissues such
      as tracheal epithelium, mast cells, lymphoid cells, and aortic endothelium, which
      are frequently exposed to oxidative stress. Therefore, we compared SERCA3 and
      SERCA2b proteins for their sensitivity to oxidation. We isolated microsomes from
      HEK-293 cells overexpressing SERCA3 or SERCA2b. We incubated the microsomes with
      different concentrations of hydrogen peroxide and then determined Ca2+ pump
      activities in them in the following three assay systems: ATP-dependent oxalate
      stimulated azide-insensitive 45Ca2+ uptake by the microsomal vesicles, Ca(2+)
      Mg(2+)-ATPase, and Ca(2+)-dependent acylphosphate formation. Peroxide inhibited
      the pump activities in microsomes with half-maximal inhibitory concentration
      (IC50) values of 69 +/- 14, 66 +/- 13, and 84 +/- 15 microM for the 45Ca2+
      uptake, Ca(2+)-Mg(2+)-ATPase, and the acylphosphate formation reactions,
      respectively. However, for microsomes from SERCA3-expressing cells, the
      corresponding values of IC50 for peroxide were 274 +/- 47, 857 +/- 110, and 746
      +/- 40 microM. Thus, in each assay system, the resistance to inactivation by
      peroxide was significantly (P < 0.05) higher for the SERCA3 protein than for
      SERCA2b. The SERCA3 resistance to oxidants may aid the cells expressing it to
      function during exposure to oxidative stress.

PMID- 9277340
TI  - Cystic fibrosis affects specific cell type in sweat gland secretory coil.
AB  - The sweat gland has three distinct cell types: a myoepithelial (ME) cell, a beta
      adrenergic-insensitive (beta-I) cell, and a beta-adrenergic-sensitive (beta-S)
      cell. Using intracellular microelectrodes, we sought to functionally identify the
      specific cell type(s) affected in cystic fibrosis (CF). We found that in CF
      secretory coils 1) the ME calls are unaffected, as indicated by normal cell
      membrane potentials and spontaneous and cholinergically induced depolarizing
      potentials, 2) the beta-I cells showed normal physiological properties, including
      a relatively smaller cell membrane potential (approx -25 mV) and a Ba(2+)
      inhibitable cholinergic response, and, in contrast, 3) the beta-S cell is
      abnormal, as shown by the lack of a beta-adrenergically activated cystic fibrosis
      transmembrane conductance regulator (CFTR) Cl- conductance (GCl). Lack of CFTR
      GCl in this cell type does not affect either the magnitude of cell membrane
      potential (approx -56 mV) or the relative cell membrane GCl or the cholinergic
      response, as compared with that of normal beta-S cells. We conclude that, of the
      three cell types in secretory coil, only the beta-S cell is specifically affected
      in the CF secretory tissue of the human sweat gland.

PMID- 9277341
TI  - Substrate-dependent expression of Na+ transport and shunt conductance in A6
      epithelia.
AB  - A6 epithelia grown in tissue culture vary enormously in their baseline rates of
      Na+ transport due to differences in growth media, serum, and other unknown
      factors. To evaluate the effect(s) of substrates on expression of Na+ transport,
      we determined short-circuit currents, open-circuit voltages, and electrical
      resistances of mature confluent A6 epithelia grown on a variety of commercially
      available permeable supports. Because the cells, growth conditions, and all other
      factors were the same, differences in transport could be attributed alone to the
      substrate on which the cells were grown. Tissues were grown on both large- and
      small-diameter inserts of the same type with differing ratios of edge length to
      area so that the contribution of the edge and tight junction conductances to the
      combined shunt conductance of the inserts could be evaluated. Shunt and cellular
      conductances and the cellular Thevenin electromotive force were determined after
      aldosterone stimulation and amiloride inhibition of Na+ transport. Marked and
      extreme differences were observed not only for expression of Na+ transport
      (controls, 0.09-3.94 microA/cm2; aldosterone, 1.53-28.2 microA/cm2) due to
      changes of apical membrane conductance but also for the development of junctional
      conductances (3,250 to < infinity omega.cm2) and edge conductances (13,175 to <
      infinity omega.cm) among substrates.

PMID- 9277342
TI  - Immuno and functional characterization of CFTR in submandibular and pancreatic
      acinar and duct cells.
AB  - Cystic fibrosis results from defective Cl- channel activity mediated by the
      cystic fibrosis transmembrane conductance regulator (CFTR) gene product. In the
      gastrointestinal tract this is manifested in abnormal salivary secretion and
      pancreatic insufficiency. This is generally attributed to defective Cl- transport
      by the ductal system of the glands. We provide the first immunocytochemical and
      functional evidence for expression of CFTR protein and Cl- current in rat and
      mouse submandibular gland (SMG) and pancreatic acinar cells, a site proximal to
      the ductal system of these secretory glands. Monoclonal and polyclonal antibodies
      recognizing COOH-terminal epitopes of CFTR show that duct and acinar cells from
      the two glands express CFTR in the luminal membrane. Specificity of the
      polyclonal antibody was verified by absence of staining in duct and acinar cells
      of the SMG of cf-/cf- and delta F/delta F mice. Identification of CFTR in acinar
      cells was aided by demonstrating coexpression of CFTR and type 3 inositol 1,4,5
      trisphosphate receptors in the luminal pole of acini and absence of type 3
      inositol 1,4,5-trisphosphate receptors in ducts. Electrophysiological
      characterization in single SMG duct and acinar cells shows the presence of a
      protein kinase A-activated, voltage- and time-independent, ohmic Cl- current and
      absence of repolarization-dependent tail currents, all of which are kinetic
      properties of the CFTR-dependent Cl- channel. In addition, the channel was
      activated by the nonhydrolyzable ATP analog 5'-adenylylimidodiphosphate and the
      benzimidazalone NS-004. Channels activated by all activators were inhibited by
      glibenclamide and a known inhibitory antiserum [anti-CFTR-(505-511)]. Combined
      immunologic, functional, and pharmacological evidence allows us to conclude that
      acinar cells of the SMG and pancreas express functional CFTR-dependent Cl-
      channels. Because this site is proximal to the duct, modification of activity of
      this channel in acinar cells is likely to contribute to abnormal salivary
      secretion and pancreatic insufficiency typical of cystic fibrosis.

PMID- 9277344
TI  - Exogenous fructose 1,6-bisphosphate reduces K+ permeability in isolated rat
      hepatocytes.
AB  - The relationship between the protective effect of fructose 1,6-bisphosphate (F
      1,6-P2) against cell injury and the modifications produced in the metabolic
      fluxes and in the membrane permeability to K+ was studied in isolated rat
      hepatocytes. Incubation of these cells in the presence of F-1,6-P2 reduced
      metabolic activity without affecting the ATP content, which suggests a
      downregulation of the ATP turnover. Using 86Rb+ as a tracer, we analyzed the
      relationship between these metabolic changes and alterations in K+ fluxes. In the
      presence of F-1,6-P2 the passive and the active K+ fluxes in hepatocytes
      decreased. However, the Na(+)-K+ pump from semipurified membranes was not
      directly affected by F-1,6-P2, which suggests a secondarily induced reduction of
      Na(+)-K+ pump activity. Moreover, galactosamine-treated cells showed a marked
      increase in permeability to K+ that was abolished by the presence of F-1,6-P2.
      This protective effect may be related to the prevention of K+ efflux. The results
      reported here strongly suggest the induction of channel arrest, and the
      associated metabolic downregulation, as the primary protective effect of F-1,6
      P2, as has been shown in the prevention of galactosamine-induced hepatotoxicity.

PMID- 9277343
TI  - Apical and basolateral membrane mechanisms that regulate pHi in bovine retinal
      pigment epithelium.
AB  - pH regulation was studied in fresh explant bovine retinal pigment epithelium
      choroid using the pH-sensitive dye 2',7'-bis(carboxyethyl)-5(6)
      carboxyfluorescein and intracellular microelectrodes. Acid recovery was HCO3
      dependent, inhibited by apical amiloride and apical or basal 4,4'
      diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), and required apical and basal
      Na. Alkali recovery was HCO3 dependent and inhibitable by apical or basal DIDS.
      Three apical and two basolateral transporters were identified. Four contribute to
      acid extrusion, i.e., apical Na/H exchange, apical H-lactate cotransport, and
      apical Na-HCO3 cotransport and basolateral Na-HCO3 cotransport. At least two
      contribute to alkali extrusion, i.e., apical Na-HCO3 cotransport and a
      basolateral HCO3-dependent, DIDS-inhibitable mechanism, possibly Na-HCO3
      cotransport, Cl/HCO3 exchange, or both. The apical Na-HCO3 cotransporter is
      electrogenic, carrying net negative charge inward. Basal Cl removal or addition
      of basal HCO3 caused HCO3- and Cl-dependent alkalinizations, respectively. Apical
      DIDS increased both responses. These cytosolic pH (pHi) regulatory mechanisms are
      so tightly coupled that changes in pHi can only occur after two or more of them
      are inhibited. In addition, these mechanisms help provide pathways for transport
      of Na and HCO3 across the retinal pigment epithelium between the blood and the
      distal retina.

PMID- 9277345
TI  - Two mechanisms by which ATP depletion potentiates induction of the mitochondrial
      permeability transition.
AB  - The present and a previous study [J. W. Snyder, J. G. Pastorino, A. M. Attie, and
      J. L. Farber, Am. J. Physiol. 264 (Cell Physiol. 33): C709-C714, 1993] define two
      mechanisms whereby ATP depletion promotes liver cell death. ATP depletion and
      cell death are linked by the mitochondrial permeability transition (MPT).
      Mitochondrial deenergization promotes the MPT, and ATP maintains a membrane
      potential by reversal of ATP synthase. With an increased influx of Ca2+ induced
      by the ionophore A-23187, oligomycin depleted the cells of ATP without loss of
      the mitochondrial membrane potential and further elevated the intracellular Ca2+
      concentration. Cyclosporin A (CyA) prevented the accompanying cell killing.
      Fructose also preserved the viability of the cells. With the increased cytosolic
      Ca2+ imposed by A-23187, viability is maintained by ATP-dependent processes. Upon
      depletion of ATP, Ca2+ homeostasis cannot be maintained, and the MPT is induced.
      Rotenone also depleted the cells of ATP, and A-23187 accelerated the loss of the
      mitochondrial membrane potential occurring with rotenone alone. CyA and fructose
      prevented the cell killing with rotenone and A-23187. Oligomycin did not prevent
      this action of fructose. We conclude that ATP is needed to maintain Ca2+
      homeostasis to prevent the MPT and the resultant liver cell death. ATP is also
      needed to maintain mitochondrial energization when electron transport is
      inhibited.

PMID- 9277346
TI  - Hormonal and neurogenic control of Na-K-ATPase and myosin isoforms in neonatal
      rat cardiac myocytes.
AB  - In the rat heart there is a postnatal switch in the expression of isoforms of
      both Na-K-ATPase and myosin heavy chain (MHC). Here we investigated factors
      controlling isoform changes in cultures of neonatal cardiomyocytes. In serum-free
      medium, the compositions of either Na-K-ATPase or MHC isoforms resembled the
      neonatal phenotype. Thyroid hormone induced the MHC isoform switch but increased
      expression of all Na-K-ATPase isoforms to various extents. Dexamethasone failed
      to induce the MHC switch and inhibited Na-K-ATPase alpha 1 isoform expression
      without inducing the other isoforms. With both hormones, the adult phenotype for
      both MHC and Na-K-ATPase was seen but with low Na-K-ATPase alpha 2. The paucity
      of alpha 2 protein was not predicted by studies of mRNA levels. In serum, there
      was a gradual decline of Na-K-ATPase alpha 3 and the appearance of alpha 2, but
      again at a relatively low level. Expression of Na-K-ATPase alpha 2 was
      significantly upregulated when cardiomyocytes were cocultured with sympathetic
      neurons from superior cervical ganglia, without changes in the MHC isoforms. Thus
      innervation is postulated to play a specific role in modulating Na-K-ATPase gene
      expression.

PMID- 9277347
TI  - M2 receptor activation of nonselective cation channels in smooth muscle cells:
      calcium and Gi/G(o) requirements.
AB  - Muscarinic stimulation of fura 2-loaded smooth muscle cells evoked a rapidly
      inactivating Ca(2+)-activated Cl- current [ICl(Ca)] and a sustained nonselective
      cation current (Icat) as well as a transient (delta Ca(tran)) and a sustained
      (delta Ca(sus)) elevation of cytosolic Ca2+ concentration ([Ca2+]i). Caffeine and
      inositol 1,4,5-trisphosphate induced delta Ca(tran) and ICl(Ca) but not Icat or
      delta Ca(sus). M2 receptor antagonism blocked muscarinic activation of Icat and
      delta Ca(sus) but not ICl(Ca) and delta Ca(tran). M3 antagonism blocked
      activation of ICl(Ca) and Icat and a rise in [Ca2+]i, but application of caffeine
      with methacholine restored Icat and delta Ca(sus). After depletion of
      intracellular Ca2+ stores, methacholine failed to induce Icat or a [Ca2+]i
      increase and, in pertussis toxin-treated cells, ICl(Ca) and delta Ca(tran) but
      not Icat or delta Ca(sus) were evoked. Anti-G alpha i-1/G alpha i-2 antibodies
      and anti-G alpha i-3/ G(o) alpha antibodies blocked Icat but did not affect
      ICl(Ca). Anti-Gq alpha/ G alpha 11 antibodies greatly inhibited ICl(Ca) but did
      not affect Icat. Activation of M2 receptors leads to the opening of nonselective
      cation channels through Gi/G(o) proteins in smooth muscle cells, resulting in a
      sustained rise in [Ca2+]i. Arise in [Ca2+]i is necessary but not sufficient for
      activation of nonselective cation channels.

PMID- 9277348
TI  - Muscarinic signaling pathway for calcium release and calcium-activated chloride
      current in smooth muscle.
AB  - We investigated the muscarinic activation of Ca(2+)-activated Cl- currents
      [ICl(Ca)] in voltage-clamped equine tracheal myocytes. The threshold of cytosolic
      free Ca2+ concentration ([Ca2+]i) required for activation of ICl(Ca) was 202 +/-
      22 nM, and full activation of the current occurred at 771 +/- 31 nM. Hexahydro
      sila-difenidol (M3 antagonist) inhibited the methacholine-induced phasic [Ca2+]i
      increase and ICl(Ca) in a concentration-dependent manner, whereas methoctramine
      (M2 antagonist) only slightly attenuated the [Ca2+]i increase and ICl(Ca) (14.8
      and 21.4%, respectively), consistent with incomplete selectivity. Dialysis of
      heparin (10 mg/ml) blocked methacholine-induced [Ca2+]i and ICl(Ca) but had no
      effect on the caffeine-induced Ca2+ release or ICl(Ca); inositol 1,4,5
      trisphosphate (100 microM) induced ICl(Ca) and blocked the methacholine current.
      Conversely, ruthenium red (50 microM) prevented the caffeine-induced [Ca2+]i
      release and ICl(Ca) but had no effect on methacholine-induced [Ca2+]i or current.
      Intracellular dialysis of the calmodulin antagonist N-(6-aminohexyl)-1
      naphthalenesulfonamide (W-7, 500 microM) or the Ca2+/calmodulin-dependent protein
      kinase inhibitor KN93 (5 microM) had no effect on the [Ca2+]i increase or
      ICl(Ca). Pertussis toxin (0.5 mg/ml) did not affect the increase in [Ca2+]i or
      ICl(Ca). Dialysis with antibodies directed against the alpha-subunit of Gq/G11
      (Gq alpha/ G alpha 11) blocked the methacholine-induced ICl(Ca) in a
      concentration-dependent manner, whereas anti-G alpha i-1/G alpha 1-2 antibodies
      (1:35) and anti-G alpha i-3/G(o) alpha antibodies (1:35) were without effect. The
      results indicate that stimulation of phospholipase C via M3/Gq proteins is the
      predominant signaling pathway for the activation of ICl(Ca); at high agonist
      concentrations, Ca(2+)-induced Ca2+ release does not appear to play a prominent
      role in muscarinic signaling.

PMID- 9277349
TI  - Ca(2+)-activated Cl- currents are activated by metabolic inhibition in rat
      pulmonary artery smooth muscle cells.
AB  - We report the electrophysiological and functional properties of Ca(2+)-activated
      Cl- currents [ICl(Ca)] in rat pulmonary artery smooth muscle and the activation
      of these currents by the metabolic inhibitor cyanide. Caffeine and norepinephrine
      (NE) evoked both Ca(2+)-activated K+ currents [IK(Ca)] and ICl(Ca) currents in
      voltage-clamped myocytes (-50 mV). Niflumic acid (10 microM) reduced the caffeine
      induced ICl(Ca) by approximately 64% and reversibly reduced NE-induced tension.
      Exposure of myocytes to cyanide (2-10 mM) induced a slowly developing inward
      current (-50 mV) in physiological and K(+)-free solutions, which was identified
      as ICl(Ca) on the basis of ion selectivity and Ca2+ dependence. Cyanide elevated
      cytosolic Ca2+ concentration, and this elevation was markedly inhibited by
      preexposure to caffeine and slightly inhibited by nisoldipine. During exposure to
      caffeine, the Ca(2+)-activated K+ current was also augmented. Cyanide markedly
      prolonged ICl(Ca) activated by caffeine, increasing the half-decay time from 3.5
      (control) to 29 s (cyanide); the half-decay time of the caffeine-induced IK(Ca)
      was not significantly affected by cyanide. The results indicate that metabolic
      inhibition increases [Ca2+]i and activates a prolonged, depolarizing Cl- current
      in pulmonary artery myocytes.

PMID- 9277350
TI  - Inhibition of intestinal Cl- secretion by clotrimazole: direct effect on
      basolateral membrane K+ channels.
AB  - We evaluated the effects of clotrimazole and clofibrate on Ca(2+)- and adenosine
      3',5'-cyclic monophosphate (cAMP)-mediated Cl- secretion in the colonic cell
      line, T84. We used 1-ethyl-2-benzimidazolinone (1-EBIO) to activate the Ca(2+)
      dependent K+ channel (KCa) in these cells to induce a sustained Cl- secretory
      current (Isc). Clotrimazole potently inhibited the KCa-dependent Isc, with an
      inhibition constant (Ki) of 0.27 +/- 0.02 microM. Clofibrate also inhibited the 1
      EBIO-induced Isc albeit with lower affinity (Ki = 6.5 +/- 1.2 microM).
      Clotrimazole (10 microM) inhibited the Isc response to the Ca(2+)-mediated
      agonist, carbachol, by 82%. Similarly, both clotrimazole and clofibrate inhibited
      cAMP-mediated Cl- secretion, with Ki values of 5.2 +/- 1.0 and 6.7 +/- 1.1
      microM, respectively. We used nystatin to permeabilize the apical or basolateral
      membrane to determine the effects of clotrimazole and clofibrate on the
      basolateral K+ (IK) and apical Cl- (ICl) currents following stimulation by either
      1-EBIO or forskolin. Both clotrimazole and clofibrate inhibited the 1-EBIO- and
      forskolin-induced IK without affecting ICl. We determined the effects of
      clotrimazole and clofibrate on KCa using 86Rb+ uptake studies into membrane
      vesicles. Both clotrimazole and clofibrate inhibited the 1-EBIO-induced 86Rb+
      uptake, with Ki values of 0.31 +/- 0.08 and 10.8 +/- 5.5 microM, respectively.
      Similarly, clotrimazole inhibited the Ca(2+)-induced 86Rb+ uptake with a Ki of
      0.51 +/- 0.15 microM. Charybdotoxin inhibited both the 1-EBIO- and Ca(2+)-induced
      86Rb+ uptakes with similar affinities (Ki values of 0.57 +/- 0.07 and 0.47 +/-
      0.08 nM, respectively), suggesting 1-EBIO and Ca2+ activate the same channel
      (KCa) in this assay. In excised, single-channel recordings both clotrimazole and
      clofibrate inhibited KCa, demonstrating a direct inhibition of the channel by
      these compounds. We demonstrate that clotrimazole blocks the intestinal KCa,
      thereby inhibiting Cl- secretion. These results suggest that clotrimazole may be
      useful as an antidiarrheal.

PMID- 9277351
TI  - Contribution of a swelling-activated chloride current to changes in the cardiac
      action potential.
AB  - The purpose of this investigation was to determine to what extent the swelling
      activated Cl- current (ICl,swell) contributes to swelling-induced changes in the
      resting membrane potential and action potential duration (APD) in ventricular
      myocytes. Action potentials were recorded from guinea pig ventricular myocytes
      using conventional whole cell recording techniques. Cell swelling caused initial
      lengthening followed by a variable shortening of APD. In 59% of cells this
      secondary APD shortening had a 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid
      (DIDS)-sensitive component, consistent with a contribution from ICl,swell.
      Furthermore, DIDS partially antagonized the depolarization of the resting
      membrane potential that occurred during cell swelling. We have modeled the
      ICl,swell using the Oxsoft Heart computer program. Action potential changes
      predicted by the model agree well with the observed DIDS-sensitive component of
      the change in the action potential during cell swelling. We conclude that
      activation of ICl,swell contributes to shortening of APD and depolarization of
      the resting membrane potential during cell swelling in cardiac myocytes.

PMID- 9277352
TI  - Prostaglandin E2 increases 7-pS Cl- channel density in the apical membrane of A6
      distal nephron cells.
AB  - In A6 distal nephron cells, short-circuit current (Isc) was increased by
      basolateral exposure to prostaglandin E2 (PGE2; peak response at 1 microM). The
      effect was only partially abolished by either apical amiloride, an Na+ channel
      blocker, or 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), a Cl- channel
      blocker. In apical cell-attached patches, we observed a 7-pS Cl- channel with a
      linear current-voltage relationship, a reversal potential near resting membrane
      potential, and open probability > 0.5. The channel was blocked by diphenylamine-2
      carboxylate, glibenclamide, and NPPB but not by 4,4'-diisothiocyanostilbene-2,2'
      disulfonic acid. The frequency of observed Cl- channel activity increased 7-fold
      with 10-min exposure to PGE2 and 3.7-fold with longer (10-50 min) exposure to
      PGE2. The PGE2-induced increase in Cl- channel activity was due primarily to an
      increase in the number of functional channels. The following conclusions were
      made: 1) activation of apical, 7-pS Cl- channels in A6 cells accounts for the
      PGE2-induced increase in the amiloride-insensitive Isc, and 2) 7-pS Cl- channel
      activation was mediated via an increase in channel density without substantial
      effects on channel kinetics.

PMID- 9277353
TI  - Adaptation to low-K+ media increases H(+)-K(+)-ATPase but not H(+)-ATPase
      mediated pHi recovery in OMCD1 cells.
AB  - Studies in rat and rabbit outer medullary collecting duct of inner stripe origin
      (OMCDis) suggest that both H(+)-ATPase and H(+)-K(+)-ATPase participate in H+
      secretion. However, the relative contributions of these transporters, and, in
      particular, that of H(+)-K(+)-ATPase to K+ absorption have not been defined
      precisely. The present study was designed to delineate more clearly the response
      of these two transporters to hypokalemia and acidosis in a newly developed mouse
      OMCD1 cell line. In cells grown in normal K+ (5 mM) media, intracellular pH (pHi)
      recovery was similar either in the presence or absence of K+ in the perfusate
      (delta pHi/min = 0.014 +/- 0.001 vs. 0.017 +/- 0.003, not significant). The
      inhibitory effects of Sch-28080 (10 microM) and bafilomycin A1 (10 nM) on pHi
      recovery were evident only in the presence and absence of K+ in the perfusate,
      respectively. In cells grown in low-K+ (2.5 mM) media to simulate chronic
      hypokalemia, pHi recovery was significantly faster than in cells grown in normal
      K+ media (delta pHi/min = 0.045 +/- 0.01 vs. 0.014 +/- 0.001, P < 0.01) and was
      inhibited specifically by Sch-28080, not by bafilomycin A1. In contrast, in cells
      preconditioned to low pH (7.0) to simulate chronic acidosis, the enhanced pHi
      recovery was abolished by bafilomycin A1 but not by Sch-28080. 86Rb+ uptake, when
      used as a K+ congener, was inhibited by Sch-28080. The K(m) for 86Rb+ uptake
      (H(+)-K(+)-ATPase activity) and the 50% inhibitory concentration for Sch-28080
      were 270 and 5.0 microM, respectively. These studies provide evidence that, in
      morphologically homogeneous OMCD1 cells, 1) both H(+)-K(+)-ATPase and H(+)-ATPase
      participate in pHi regulation, 2) the H(+)-K(+)-ATPase is selectively upregulated
      by preconditioning in low-K+ media, and 3) conversely, preconditioning in low-pH
      media stimulates only the H(+)-ATPase. Thus, in OMCDis, the H(+)-K(+)-ATPase and
      H(+)-ATPase respond selectively and independently to chronic hypokalemia and
      acidosis, respectively.

PMID- 9277354
TI  - Differential activation of NF-kappa B in human aortic endothelial cells
      conditioned to specific flow environments.
AB  - Endothelial cell-monocyte interaction plays an important role in atherogenesis.
      The expressions of some endothelial cell adhesion molecules involved in
      endothelial cell-monocyte interactions are regulated by transcription factor NF
      kappa B. Because low shear stress has been known to influence endothelial
      monocyte adhesion, the differential activation of NF-kappa B under different flow
      regimens across time (0.5-24 h) was investigated. Nuclear proteins from flow
      conditioned human aortic endothelial cells (HAEC) were analyzed by
      electrophoretic mobility shift assay using [gamma-32P]dATP-labeled NF-kappa B
      specific oligonucleotide. Our results demonstrated that NF-kappa B activation was
      significantly elevated in HAEC exposed to prolonged (> 2 h) steady low shear (2
      dyn/cm2) and pulsatile low shear (2 +/- 2 dyn/cm2) compared with HAEC exposed to
      high shear (16 dyn/cm2). In contrast, at 30 min, high shear-exposed HAEC
      exhibited an early, transient increase in NF-kappa B activity, relative to low
      shear-exposed cells, which reversed on continued exposure to high shear. Maximum
      activity in both low shear- and pulsatile low shear-conditioned HAEC was observed
      at 16 h compared with HAEC exposed to prolonged high shear. These results
      indicate that exposure of HAEC to prolonged low shear conditions is associated
      with significantly increased and prolonged NF-kappa B activity. This observation
      might provide a mechanism to explain the increased monocyte adhesion in
      atherosclerosisprone arterial sites exposed to chronic low-shear flow patterns.

PMID- 9277355
TI  - Apoptosis: a mechanism contributing to remodeling of skeletal muscle in response
      to hindlimb unweighting.
AB  - The role of apoptosis in the elimination of myonuclei during hindlimb unloading
      induced atrophy and the inhibition of apoptosis in the prevention of muscle
      atrophy were examined. The number of nuclei demonstrating double-stranded DNA
      fragmentation seen by terminal deoxynucleotidyl transferase (TDT) histochemical
      staining, an indicator of apoptosis, was significantly increased after 14 days of
      suspension. Double staining with TDT and antilaminin immunohistochemistry
      revealed that some TDT-positive nuclei were within the fiber lamina and were most
      likely myonuclei. The number of fibers containing morphologically abnormal nuclei
      was also significantly greater in suspended compared with control rats. Combined
      treatment with growth hormone and insulin-like growth factor I (GH/ IGF-I) and
      resistance exercise attenuated the increase in TDT-positive nuclei (approximately
      26%, P > 0.05) and significantly decreased the number of fibers with
      morphologically abnormal nuclei. The data suggest that 1) "programmed nuclear
      death" contributes to the elimination of myonuclei and/or satellite cells from
      atrophying fibers, and 2) GH/IGF-I administration plus muscle loading ameliorates
      the apoptosis associated with hindlimb unloading.

PMID- 9277357
TI  - Different effects of raised [K+]o on membrane potential and contraction in mouse
      fast- and slow-twitch muscle.
AB  - Increasing extracellular K+ concentration ([K+]o) from 4 to 7-14 mM reduced both
      tetanic force and resting membrane potential (Em) in isolated slow-twitch soleus
      and fast-twitch extensor digitorum longus (EDL) muscles of the mouse. The tetanic
      force-[K+]o relationships showed a greater force loss over 8-11 mM [K+]o in
      soleus than EDL, mainly because the Em was 2-3 mV less negative at each [K+]o in
      soleus. The tetanic force-resting Em relationships show that force was reduced in
      two phases: phase 1 (Em < -60 mV), a 20% force decline in which the relationships
      superimposed in soleus and EDL, and phase 2 (Em -60 to -55 mV), a marked force
      decline that was steeper in EDL than soleus. Additionally in phase 2, longer
      stimulation pulses restored tetanic force; the twitch force-stimulation strength
      relationship was shifted toward higher voltages; caffeine, a myoplasmic Ca2+
      concentration elevator, increased maximum force; and twitch force fell abruptly.
      We suggest that 1) the K(+)-depressed force is due to reduced Ca2+ release
      resulting from an altered action potential profile (phase 1) and inexcitable
      fibers due to an increased action potential threshold (phase 2), and 2) K+
      contributes to fatigue in both fast- and slow-twitch muscle when it causes
      depolarization to about -60 mV.

PMID- 9277356
TI  - Functional properties of conditioned skeletal muscle: implications for muscle
      powered cardiac assist.
AB  - Latissimus dorsi (LD) muscles of six canines were studied to assess changes
      induced by electrical conditioning and to quantify the capacity of these muscles
      to perform hemodynamic work. Muscles were conditioned using burst stimuli
      delivered over an 8-wk period. Contralateral LD were used as control. Muscles
      were tested in situ to simulate anticipated linear-pull cardiac assist
      conditions. This training process reduced muscle mass and cross-sectional area by
      16 and 17%, respectively. Muscle phenotype shifted to a predominantly "slow" form
      by coordinate reduction of myosin heavy chain (MHC) 2A expression and increased
      expression of the MHC beta/slow form. Force generation was reduced by 54%, and
      contractile duration increased 13%. Fatigue resistance was markedly enhanced, and
      chronic stroke work increased from 0.19 to 0.72 mJ/g. The highest steady-state
      power output (2.06 mW/g) was obtained from one muscle fully converted to a slow
      phenotype. These data suggest that single LD trained via conventional techniques
      can provide energy sufficient for partial cardiac assistance but cannot sustain
      work levels needed to achieve total circulatory support.

PMID- 9277358
TI  - Cholinergic modulation of the Ca2+ response to bradykinin in neuroblastoma cells.
AB  - Fura 2 imaging was used to measure intracellular Ca2+ signals in N1E-115 mouse
      neuroblastoma cells during combined activation of bradykinin (BK) and cholinergic
      receptors. BK and carbachol (CCh) both activate phospholipase C (PLC) and cause
      Ca2+ release from inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ stores. The
      Ca2+ signal in response to CCh is prolonged by the activation of Ca2+ influx, but
      BK does not appear to activate the influx pathway. When BK and CCh are applied
      together (BK+CCh), the Ca2+ response is composed of both Ca2+ release and Ca2+
      influx. Ca2+ influx is also activated by BK+CCh in a subset of cells that does
      not respond with a intracellular Ca2+ concentration increase when CCh is
      presented by itself. This suggests that CCh stimulates a Ca(2+)-silent
      cholinergic receptor that is not coupled to Ca2+ release but acts synergistically
      with BK receptors to activate Ca2+ influx. Pertussis toxin reduces influx without
      affecting release, indicating that the G protein that modulates the influx
      pathway is different from the G protein responsible for activating PLC.
      Cholinergic stimulation also causes progressive heterologous desensitization of
      BK-evoked Ca2+ release. Desensitization has the unique property of continuing to
      develop after the cholinergic agonist is removed and the cholinergic Ca2+
      response has fully recovered. Heterologous desensitization is not the result of
      Ca2+ store depletion or a long-lasting inhibition of PLC or IP3-dependent Ca2+
      release. Instead, it appears to involve an early step in the BK-signaling
      cascade, possibly at the level of the B2 receptor or associated G proteins.

PMID- 9277359
TI  - Suppression of neuropeptide Y1 receptor function in SK-N-MC cells by nitric
      oxide.
AB  - The neuropeptide Y1 receptor (NPY1) predominantly mediates the vasoconstrictor
      effects of NPY in smooth muscle cells. The present experiments were planned to
      study the direct influence of the vasodilator nitric oxide (NO) on NPY1-receptor
      function. SK-N-MC and CHP-234 cells expressing Y1 and Y2 receptor, respectively,
      were incubated with the NO donors sodium nitroprusside (SNP), 3
      morpholinosydnonimine (SIN-1), and S-nitroso-N-acetyl-penicillamine (SNAP).
      Receptor binding, Y1-receptor mRNA expression by Northern blot, and adenosine
      3',5'-cyclic monophosphate (cAMP) and intracellular Ca2+ concentration ([Ca2+]i)
      responses were studied. SNP, SIN-1, and SNAP decreased normal binding of NPY to
      the NPY1 receptor in SK-N-MC cells in a concentration-dependent manner. SNP (500
      microM), SIN-1 (1,000 microM), and SNAP (500 microM) significantly decreased
      binding to approximately 50%. The cell viability was not reduced. None of the NO
      donors affected Y2 receptor binding. Pretreatment with SNP significantly
      attenuated NPY-induced inhibition of cAMP formation in SK-N-MC cells but had no
      effect on CHP cells. The NPY-induced [Ca2+]i response was reduced to 50% by SNP
      pretreatment. NPY1 mRNA expression was reduced to one-third after SNAP treatment
      of SK-N-MC cells. In vitro, NPY1 receptor function of SK-N-MC cells is inhibited
      by NO-donor incubation on an mRNA level.

PMID- 9277360
TI  - Regulation of native Kv1.3 channels by cAMP-dependent protein phosphorylation.
AB  - We present evidence that activity of native Kv1.3 channels in human T lymphocytes
      can be increased by inhibiting phosphatases [using okadaic acid (OA)] or by
      activating protein kinase A (PKA). OA increased the maximal conductance (Gmax) by
      40% and shifted the voltage dependence of activation and inactivation, resulting
      in a significant increase in window current around the normal membrane potential.
      PKA inhibition [using the PKA inhibitor peptide PKI-(5-24)] decreased Gmax by
      43%, whereas PKA activation [by the Sp diastereomer of adenosine 3',5'-cyclic
      monophosphothioate (Sp-cAMPS)] increased Gmax by 60% and shifted the inactivation
      curve, producing an increase in the window current. These results are consistent
      with our previously published work using cell-attached patches but differ from
      some studies of Kv1.3. Because we previously reported a similar upregulation by
      protein kinase C (PKC) activation in these cells, we tested whether the PKA and
      PKC effects were additive. Our results suggest that PKC-dependent phosphorylation
      acts as a master switch, inasmuch as calphostin C greatly inhibited the current
      even after Sp-cAMPS, OA, or PKC activation was used to increase protein
      phosphorylation. Inasmuch as phosphorylation by both kinases (phorbol ester
      followed by Sp-cAMPS) abrogated the effects of either kinase alone, our results
      support the view that Kv1.3 is regulated in a complex manner by serine/threonine
      phosphorylation.

PMID- 9277361
TI  - Ammonia effect on calcium-activated chloride secretion in T84 intestinal
      epithelial monolayers.
AB  - We recently showed that ammonia profoundly inhibits cyclic nucleotide-regulated
      Cl- secretion in model human T84 intestinal epithelia but does not impair the
      secretory response to the Ca2+ agonist carbachol. Using transepithelial
      transport, fura 2 fluorescence, and radioisotopic efflux techniques, we further
      explored this dichotomy and arrived at a preliminary explanation for the
      inhibitory action of ammonia. The secretory response to the Ca(2+)
      adenosinetriphosphatase inhibitor thapsigargin is unaffected by ammonia, which
      suggests that an increase in intracellular Ca2+ stimulates secretory pathways
      that are insensitive to ammonia. Surprisingly, Cl- secretion elicited by the Ca2+
      ionophores ionomycin and A23187 is markedly blunted in monolayers pretreated with
      ammonia. However, ammonia posttreatment does not inhibit the secretory response
      to ionophore, which suggests that ammonia may interfere with the ability of these
      ionophores to increase intracellular [Ca2+]. This hypothesis is directly
      supported by fura 2 experiments. The inhibitory action of ammonia parallels the
      behavior of the K+ channel blocker Ba2+, and ammonia reduces the basolateral
      86Rb+ efflux rate constant in forskolin- but not in carbachol-treated monolayers.
      Ammonia, which is present in high concentrations in the normal gastro-intestinal
      tract, may serve as a novel endogenous regulator of epithelial electrolyte
      transport by interfering with a Ba(2+)-sensitive basolateral K+ conductance
      distinct from the Ca(2+)-activated basolateral K+ conductance.

PMID- 9277362
TI  - Dual modulation of Na/H antiport by atrial natriuretic factor in rat aortic
      smooth muscle cells.
AB  - The aim of the present work was to study the effect of the atrial natriuretic
      factor (ANF) on the Na/H antiport in rat aorta smooth muscle cells, evaluated as
      intracellular pH (pHi) recovery after an acid load with ammonium chloride. The
      Na/H antiport was studied using a fluorescent probe, sensitive to pHi, 2',7'
      bis(carboxyethyl)-5(6)-carboxyfluorescein. Our data indicate that ANF modulates
      the activity of the Na/H antiport in both a dose- and time-dependent manner.
      Hormone concentrations of 10(-10) M activate the antiport, increasing both the
      rate of recovery and the set point by approximately 0.2 pH units. This effect is
      mediated by diacylglycerol as a result of phospholipid hydrolysis by a
      phospholipase C, even if an involvement of adenosine 3',5'-cyclic monophosphate
      (cAMP) cannot be ruled out. ANF (10(-7) M) inhibits the antiport, decreasing both
      the rate of recovery and the set point by approximately 0.3 pH units, because of
      guanosine 3',5'-cyclic monophosphate production. Both inhibition and stimulation
      of pHi by ANF were more pronounced when the hormone was given before the acid
      load, perhaps because of the longer time exposure. We present new hypotheses on
      the mechanism of action of this paracrine/autocrine factor.

PMID- 9277363
TI  - Neutrophil-mediated phospholipid peroxidation assessed by gas chromatography-mass
      spectroscopy.
AB  - Disease pathophysiology frequently involves manifestations of the systemic
      inflammatory response syndrome. Oxyradicals represent key inflammatory mediators,
      and neutrophils are one important source of oxyradicals. This investigation
      examined neutrophil-mediated peroxidation of dilinoleoyl phosphatidyl-choline
      (DLPC) liposomes by monitoring the appearance of monohydroxyl linoleic acid with
      the use of gas chromatography-mass spectroscopy (GC-MS), compared with
      traditional assessment of thiobarbituric acid-reactive species (TBARS) and
      phosphatidylcholine-specific conjugated dienes. DLPC was peroxidized in a system
      using activated neutrophils in balanced salt solution containing chelated iron. 9
      Monohydroxyl linoleic acid and 13-monohydroxyl linoleic acid were readily
      identified in neutrophil-mediated peroxidized DLPC with the use of GC-MS.
      Neutrophil NADPH oxidoreductase specific activity correlated highly with total
      ion current or specific ion monitoring of integrated peak areas for peroxidized
      linoleic acid but correlated poorly with DLPC-derived TBARS or conjugated dienes.
      These results ascertain that activated neutrophils mediate phosphatidylcholine
      lipid peroxidation to specific products, which may be precisely monitored with
      the use of GC-MS. The extent of this peroxidation is highly correlated with the
      magnitude of the neutrophil respiratory burst.

PMID- 9277364
TI  - Actin removal from cardiac myocytes shows that near Z line titin attaches to
      actin while under tension.
AB  - The I band of cardiac sarcomeres contains both actin and titin/connectin
      filaments. Earlier work has suggested that titin binds to actin in situ. This
      interaction must be weak in the region of the I band where titin behaves
      elastically. On the other hand, titin may bind strongly to actin in the
      approximately 100-nm-wide region adjoining the Z line, where titin has been found
      to be inelastic. To study the putative interaction between titin and actin,
      techniques for selective removal of actin from different regions of the I band
      are needed. Here we report studies with a gelsolin fragment (FX-45) and extract
      actin from rat cardiac myocytes. Actin extraction was biphasic: the majority of
      actin was extracted in approximately 10 min, whereas actin near the Z line (where
      titin is inelastic) required a approximately 10-fold longer extraction time.
      Thus, by controlling the extraction time, we could remove either the full actin
      filament outside the Z line or just the segment of the actin filament that
      extends beyond the inelastic region of titin that adjoins the Z line. The actin
      filament-free I band contained titin filaments, typically with one filament
      extending from each thick filament. In addition, we observed a dark transverse
      line (junction line), the location of which in the sarcomere varied linearly with
      sarcomere length. The position in the sarcomere of the junction line coincided
      with the binding site of the anti-titin antibody 9D10. Actin removal
      significantly affected the slack sarcomere length. Slack sarcomere length was
      1.85 +/- 0.04 microns in control cells and decreased to 1.71 +/- 0.05 microns
      after actin near the Z line was extracted. This length reduction may be caused by
      contraction of the titin segment that becomes exposed after actin removal near
      the Z line, indicating that titin is not only attached to the actin filament but
      is also under tension.

PMID- 9277365
TI  - Protein kinase and Ca2+ modulation of myo-inositol transport in cultured retinal
      pigment epithelial cells.
AB  - The acute regulation of inwardly directed Na(+)-myo-inositol (MI) cotransporter
      activity and basal and volume-sensitive MI efflux by protein kinases C (PKC) and
      A (PKA), cytosolic Ca2+, and phosphoinositide (PI) turnover were characterized in
      cultured human retinal pigment epithelial cells using 2-[3H]MI and liquid
      scintillation spectrometry. Kinetic analysis revealed two distinct Na(+)-MI
      cotransporter components differing in apparent Michaelis constant and maximal
      velocity. Composite Na(+)-MI cotransport activity was stimulated by PKA
      activation, the muscarinic agonist carbachol, and the Ca2+ ionophore A-23187 and
      was inhibited by PKC activation. PKC activation also increased MI efflux, but
      only the volume-sensitive component, whereas PKA activation increased both basal
      and volume-sensitive MI efflux. These studies implicate PKC as a negative
      modulator of MI content through Na(+)-MI cotransport inhibition and potentiation
      of volume-sensitive MI efflux. PKA is a positive modulator of both Na(+)-MI
      cotransport and basal and volume-sensitive MI efflux. Cytosolic Ca2+ release
      through receptor-mediated PI hydrolysis may facilitate Na(+)-MI cotransport
      activity.

PMID- 9277366
TI  - Effects of P2 purinergic receptor stimulation in brown adipocytes.
AB  - Sympathetic stimulation of brown adipocytes plays a major role in body energy
      homeostasis by activating energy-wasting pathways. Sympathetic neuronal input
      initiates a variety of metabolic, developmental, and membrane responses in brown
      fat cells. Many of these actions are mediated by adrenergic pathways mobilized by
      released norepinephrine. However, since sympathetic stimulation may also release
      vesicular ATP, we tested brown fat cells for ATP responses. Micromolar
      concentrations of extracellular ATP had a number of effects on brown adipocytes.
      We have shown previously that ATP elicits substantial (average of approximately
      30%) increases in cell membrane capacitance (P. A. Pappone and S. C. Lee, J. Gen.
      Physiol. 108: 393-404, 1996). Here, we show that cytosolic calcium levels were
      increased by ATP, both through release from intracellular stores and through
      influx, as assessed by fura 2 imaging. In addition, ATP indirectly activated a
      nonselective cation conductance that was independent of cytosolic calcium levels
      in patch voltage-clamped brown fat cells. Similar calcium, conductance, and
      capacitance responses could be activated by 2-methylthio-ATP and ADP, consistent
      with mediation by a P2 type purinergic receptor. Calorimetric measurements from
      cell suspensions showed that ATP increased basal heat production of isolated
      brown fat cells by approximately 40% but had no effect on the greater than
      fivefold increase in heat production seen with maximal adrenergic stimulation.
      These myriad responses to extracellular ATP suggest that P2 receptor-mediated
      signaling is important in brown adipocyte physiology and that sympathetic
      stimulation may normally activate purinergic as well as adrenergic pathways in
      brown fat.

PMID- 9277367
TI  - Experimentally induced changes in the endocytic traffic of P-glycoprotein alter
      drug resistance of cancer cells.
AB  - The MDR-1 gene product, plasma membrane glycoprotein or P-glycoprotein (PGP), has
      been shown to confer drug resistance to cancer cells by acting as an energy
      dependent drug-efflux pump. We have examined the endocytic traffic of PGP in
      human multidrug-resistant cells and tested whether the traffic and the steady
      state intracellular localization of PGP can be experimentally modulated. Here we
      show that 1) under steady state approximately 70% of cellular PGP is on the
      surface whereas approximately 30% is intracellular, 2) surface PGP undergoes
      constitutive endocytosis and recycling, 3) endocytosis of PGP involves clathrin
      and adaptin complex 2-dependent mechanism, and 4) PGP cycles through a Rab5
      responsive endosomal compartment. Biochemical (such as antibody crosslinking of
      PGP or treatment of cells with chloroquine) and molecular (such as overexpression
      of Rab5) treatments were used to modulate the endocytic/ recycling traffic of
      PGP. Such treatments resulted in the redistribution of PGP from the cell surface
      to intracellular compartments. Cells with such "mislocalized" PGP showed a
      decrease in multidrug resistance, suggesting that clinically relevant strategies
      can be attempted by modulating PGP's temporal and spatial distribution within
      cancer cells.

PMID- 9277368
TI  - Occurrence and putative hormone regulatory function of a constitutive heme
      oxygenase in rat pancreatic islets.
AB  - Recent observations suggest that carbon monoxide (CO) may serve as a
      neuroendocrine modulator in hypothalamus. Here we provide evidence, for the first
      time, that the islets of Langerhans contain the constitutive isoform of the CO
      producing enzyme heme oxygenase (HO-2), the activity of which was found to
      modulate islet hormone release. Most insulin and glucagon cells in the rat
      endocrine pancreas expressed strong immunoreactivity for HO-2. In the exocrine
      parenchyma, scattered HO-2-positive ganglionic cell bodies were occasionally
      observed. Furthermore, Western blot analysis revealed the presence of HO-2 in
      isolated islets but not in acinar cells. Islet homogenates displayed a
      comparatively high HO-2 enzymatic activity measured as CO formation
      (approximately 600 pmol CO.min-1.mg islet protein-1). This HO-2 enzymatic
      activity was greatly suppressed by zincprotoporphyrin-IX (ZnPP-IX), a recognized
      inhibitor of HO activity. Neither ZnPP-IX nor the HO activator, hemin, influenced
      basal insulin release from isolated rat islets at low (1 mM) glucose. However,
      glucagon release at 1 mM glucose was increased by hemin and inhibited by ZnPP-IX.
      The hemin-induced increase in glucagon secretion was abolished by ZnPP-IX.
      Furthermore, a series of experiments at high glucose (16.7 mM) revealed that
      hemin induced a dose-dependent potentiation of glucose-stimulated insulin
      release. Moreover, glucose-induced insulin release was dose-dependently
      suppressed by ZnPP-IX but unaffected by protoporphyrin-IX, a compound known not
      to influence HO-2 activity in other tissues. Similarly, glucagon release at high
      glucose was dose-dependently increased by hemin and suppressed by ZnPP-IX.
      Finally, the hemin-induced increase in islet hormone release at high glucose was
      totally abolished by ZnPP-IX. The data strongly suggest that CO production
      positively modulates both glucagon and insulin secretion. We propose that CO may
      serve as a novel messenger molecule within the islets of Langerhans.

PMID- 9277370
TI  - Minimal model of beta-cell mitochondrial Ca2+ handling.
AB  - We develop a simplified, but useful, mathematical model to describe Ca2+ handling
      by mitochondria in the pancreatic beta-cell. The model includes the following six
      transport mechanisms in the inner mitochondrial membrane: proton pumping via
      respiration and proton uptake by way of the F1Fzero-ATPase (adapted from D.
      Pietrobon and S. Caplan. Biochemistry 24: 5764-5778, 1985), a proton leak,
      adenine nucleotide exchange, the Ca2+ uniporter, and Na+/Ca2+ exchange. Each
      mechanism is developed separately into a kinetic model for the rate of transport,
      with parameters taken from experiments on isolated mitochondrial preparations.
      These mechanisms are combined in a modular fashion first to describe state 4
      (nonphosphorylating) and state 3 (phosphorylating) mitochondria with
      mitochondrial NADH and Ca2+ concentrations as fixed parameters and then to
      describe Ca2+ handling with variable mitochondrial Ca2+ concentration.
      Simulations are compared to experimental measurements and agree well with the
      threshold for Ca2+ uptake, measured mitochondrial Ca2+ levels, and the influence
      of Ca2+ on oxygen uptake. In the absence of Ca2+ activation of mitochondrial
      dehydrogenases, the simulations predict a significant reduction in the rate of
      production of ATP that involves a "short circuit" via Ca2+ uptake through the
      uniporter. This effect suggests a potential role for mitochondrial Ca2+ handling
      in determining the ATP-ADP ratio in the pancreatic beta-cell.

PMID- 9277369
TI  - Unopposed phosphatase action initiates ezrin dysfunction: a potential mechanism
      for anoxic injury.
AB  - Because extensive kinase inhibition during anoxia has previously been reported,
      we investigated the role of kinase inhibition in anoxic cell injury by studying
      the effects of kinase inhibitors on a membrane-microvillar cytoskeleton linker
      protein, ezrin, in rabbit renal proximal tubules. Like anoxia, kinase inhibitors
      caused ezrin dephosphorylation in a dose-dependent manner under normoxia. The
      kinase inhibitor chelerythrine also induced ezrin dissociation from the
      cytoskeleton, i.e., causing it to lose its membrane-cytoskeleton linker function.
      Blockage of kinase inhibitor-induced ezrin dephosphorylation by a phosphatase
      inhibitor, calyculin A, ameliorated ezrin dissociation. Stimulation of the kinase
      during anoxia did not improve ezrin phosphorylation, suggesting that anoxia
      induced kinase inhibition might be due to the lack of the substrate ATP. Finally,
      in vitro study of ezrin phosphatase revealed no increase in its activity during
      anoxia, suggesting the principal role of kinase inhibition in the loss of the
      linker function of ezrin during anoxia. Our results provide, for the first time
      at the molecular level, a mechanistic insight into anoxic cell injury caused by
      unopposed phosphatase action.

PMID- 9277371
TI  - Normalization of ion transport in murine cystic fibrosis nasal epithelium using
      gene transfer.
AB  - The murine nasal epithelium was investigated by the short-circuit current (SCC)
      technique. Electrogenic sodium absorption was revealed by addition of amiloride
      and calcium-dependent chloride secretion by the addition of amiloride and calcium
      dependent chloride secretion by the addition of 2,5-di-(tert-butyl)-1,4
      benzohydroquinone (TBHQ)/ionomycin. In the presence of these agents a further
      increase in SCC was obtained by addition of forskolin. Epithelia from both cystic
      fibrosis (CF) null (Cftrtm1Cam) and CF delta F508 (Cftrtm2Cam) mice had enhanced
      sodium absorption compared with controls, whereas only delta F508 epithelia had
      increased calcium-dependent chloride secretion. Both strains gave nasal epithelia
      that showed significantly reduced responses to forskolin, due to the absence of
      CF transmembrane conductance regulator (CFTR) chloride channels. In Cftrtm2Cam
      nasal epithelia the forskolin responses were not significantly different from
      zero. Transfection of these mice with the plasmid pTRIAL10-CFTR2 complexed with
      cationic liposomes normalized the transporting activity in the nasal epithelium.
      Basal SCC and calcium-dependent chloride secretion were significantly reduced,
      whereas CFTR-dependent chloride secretion was increased to normal values.
      Amiloride-sensitive SCC was reduced by transfection but failed to reach
      significance. The similarity of murine CF nasal epithelium to that in human CF
      airways makes the model valuable for gene therapy studies.

PMID- 9277372
TI  - Differential effects of creatine kinase isoenzymes and substrates on regeneration
      in livers of transgenic mice.
AB  - Creatine kinase (CK) has been implicated in affecting cell growth, and the CK
      substrates creatine (Cr) and cyclocreatine (CyCr) have been shown to have anti
      tumor activity. The influence of Cr and CyCr on liver regeneration following
      major hepatectomy was evaluated in normal and transgenic mice expressing the
      human ubiquitous mitochondrial isoform of CK (CK-mit) or the brain isoform of CK
      (CK-B) or livers expressing both CK-mit and CK-B (CK-comb). Expression of CK
      isoenzymes had little effect on liver regeneration in the absence of dietary
      supplementation with Cr or CyCr as assayed by the increase in liver mass. Dietary
      supplementation with Cr and CyCr significantly reduced liver growth in normal
      mice. Liver regeneration was almost completely inhibited in mice expressing CK
      mit in the presence of Cr. Livers expressing CK-mit regenerated better than
      normal livers in the presence of CyCr. In mice expressing CK-B, Cr and CyCr had
      opposite effects from those found in CK-mit mice. In the presence of CyCr,
      regeneration was inhibited in livers expressing CK-B, and, in the presence of Cr,
      CK-B-expressing livers regenerated better than normal livers. The amount of DNA
      synthesized 2 days after hepatectomy confirmed the results obtained from
      measurements of liver mass for all groups. Growth and DNA synthesis were
      completely abolished by Cr in CK-mit mice, whereas CyCr mainly affected growth 2
      days after hepatectomy in CK-B-expressing mice. Coexpression of the CK isoforms
      in CK-comb mice ameliorated the effects detected with either isoform alone.
      Inhibition of growth by Cr and CyCr was not correlated to water accumulation.
      These results clearly demonstrate isoenzyme and substrate-specific effects of CK
      on cell growth.

PMID- 9277373
TI  - Genistein activates CFTR Cl- channels via a tyrosine kinase- and protein
      phosphatase-independent mechanism.
AB  - Previous studies have revealed an adenosine 3',5'-cyclic monophosphate (cAMP)
      independent activation of cystic fibrosis transmembrane conductance regulator
      (CFTR) Cl- channels by the tyrosine kinase inhibitor genistein. To further
      explore its mechanism of action, we have reconstituted genistein activation of
      CFTR in excised inside-out membrane patches. In the presence or absence of ATP,
      genistein appeared unable to open silent CFTR Cl- channels. However, on CFTR
      prephosphorylation by cAMP-dependent protein kinase (cAK), genistein enhanced
      CFTR activity by twofold, resulting from a prolonged burst duration. Genistein
      could also hyperactivate partially phosphorylated CFTR in the absence of cAK and
      therefore is different from 5'-adenylylimidodiphosphate, which required fully
      phosphorylated CFTR. Phosphatase-resistant thiophosphorylation likewise primed
      the CFTR Cl- channel for hyperactivation by genistein in the absence of cAK.
      Replacement of ATP by GTP as a hydrolyzable nucleotide triphosphate for CFTR did
      not impair the ability of genistein to activate thiophosphorylated CFTR, despite
      the fact that GTP is a poor substrate for tyrosine kinases. These findings argue
      against a role of protein phosphatases or tyrosine kinases but suggest a more
      direct interaction of genistein with CFTR, possibly at the level of the second
      nucleotide-binding domain.

PMID- 9277374
TI  - Metabolic responses from rest to steady state determine contractile function in
      ischemic skeletal muscle.
AB  - Skeletal muscle contraction during ischemia, such as that experienced by
      peripheral vascular disease patients, is characterized by rapid fatigue. Using a
      canine gracilis model, we tested the hypothesis that a critical factor
      determining force production during ischemia is the metabolic response during the
      transition from rest to steady state. Dichloroacetate (DCA) administration before
      gracilis muscle contraction increased pyruvate dehydrogenase complex activation
      and resulted in acetylation of 80% of the free carnitine pool to acetylcarnitine.
      After 1 min of contraction, phosphocreatine (PCr) degradation in the DCA group
      was approximately 50% lower than in the control group (P < 0.05) during
      conditions of identical force production. After 6 min of contraction, steady
      state force production was approximately 30% higher in the DCA group (P < 0.05),
      and muscle ATP, PCr, and glycogen degradation and lactate accumulation were lower
      (P < 0.05 in all cases). It appears, therefore, that an important determinant of
      contractile function during ischemia is the mechanisms by which ATP regeneration
      occurs during the period of rest to steady-state transition.

PMID- 9277375
TI  - Chronic electrical stimulation increases MCT1 and lactate uptake in red and white
      skeletal muscle.
AB  - We examined whether chronic stimulation of red and white rat muscles increased
      the concentrations of the monocarboxylate transporter MCT1. Red and white
      tibialis anterior (RTA and WTA, respectively) and extensor digitorum longus (EDL)
      muscles were chronically stimulated via the peroneal nerve for 7 days. Stimulated
      and contralateral control muscles were examined for MCT1 content, L-lactate
      uptake, lactate dehydrogenase (LDH) isoforms, and muscle fiber composition. MCT1
      was 1.5 times greater in stimulated RTA, 3 times greater in stimulated WTA, and
      1.9 times greater in stimulated EDL compared with respective control muscles (P <
      0.05). L-Lactate uptake increased in all stimulated muscles (P < 0.05), and this
      was highly correlated with the increase in MCT1 (r = 0.96). The heart-type LDH (H
      LDH) subunits also increased in all stimulated muscles (P < 0.05). The H-LDH
      subunits correlated highly with MCT1 in the muscles (r = 0.83). There was no
      change in muscle-type LDH subunits (P > 0.05). There were negligible alterations
      in muscle fiber composition in the stimulated muscles, suggesting that the
      increase in MCT1 was independent of changes in muscle fiber composition. These
      studies are the first to demonstrate that chronic muscle contraction increases
      MCT1 concentrations in both red and white skeletal muscles.

PMID- 9277376
TI  - Effects of triiodothyronine administration on the adenylyl cyclase system in
      brown adipose tissue of rat.
AB  - This study was undertaken to investigate the effect of triiodothyronine (T3)
      administration to euthyroid rats on beta 3-adrenoceptor (beta 3-AR) expression
      and on the different components of the adenylyl cyclase (AC) system in brown
      adipose tissue (BAT). In rats treated with T3, the beta 3-AR density (assessed by
      the binding of [3H]CGP-12177) showed a decrease of 50%, as did their mRNA, as
      analyzed by reverse transcriptase-polymerase chain reaction. In hyperthyroid
      rats, compared with control rats, there was a 40% increase in G alpha s activity
      (stimulated by NaF or GTP gamma S) and a fourfold increase in the protein
      concentration (Western blotting). In contrast, the level of the pertussis toxin
      substrate Gi declined by 35% in response to T3. Analysis of dose-response curves
      for isoproterenol and CGP-12177 revealed that neither basal nor stimulated AC
      activities nor 50% stimulatory concentration for these agonists was changed by T3
      administration. In conclusion, these results suggest that downregulation of the
      beta 3-AR by T3 was counter-balanced by changes in other components of the AC
      cascade (i.e., Gs and Gi), so no change occurred in the capacity of BAT to
      generate adenosine 3',5'-cyclic monophosphate.

PMID- 9277377
TI  - Insulin resistance in adipocytes after downregulation of Gi subtypes.
AB  - To determine whether downregulation of Gi proteins is associated with insulin
      resistance, we incubated isolated adipocytes with N6-(2-phenylisopropyl)adenosine
      (PIA; an A1-adenosine receptor agonist; 300 nM), prostaglandin E1 (PGE1; 3
      microM), or nicotinic acid (1 mM) for 4 days in primary culture. The cells were
      washed, and the rate of glucose transport (2-deoxy-[3H]glucose uptake) was
      measured after incubation with various concentrations of insulin for 45 min. Both
      PIA and PGE1 (which downregulate Gi) decreased the maximal responsiveness of the
      cells to insulin by approximately 30% and caused a rightward shift in the dose
      response curve. By contrast, nicotinic acid (which does not downregulate Gi) did
      not alter the insulin sensitivity of the cells. Prolonged treatment of adipocytes
      with either PIA or PGE1 (but not nicotinic acid) rendered the cells completely
      resistant to the antilipolytic effect of insulin. The ability of insulin to
      stimulate autophosphorylation of the beta-subunit of the insulin receptor was
      decreased by approximately 30% in PIA-treated cells, and the dose-response curve
      was shifted to the right. Similarly, the ability of the receptor to phosphorylate
      poly(Glu4-Tyr1) was decreased by approximately 35%. This decrease in tyrosine
      kinase activity of the receptor may account for the decrease in insulin
      sensitivity of glucose transport but cannot account for the complete loss of
      antilipolysis. The findings suggest both a direct and indirect involvement of Gi
      proteins in insulin action.

PMID- 9277378
TI  - Interleukin-6 secretion in mice is associated with reduced glucose-6-phosphatase
      and liver glycogen levels.
AB  - Mice bearing interleukin-6 (IL-6)-secreting tumor were used to study the chronic
      effect of IL-6 on carbohydrate metabolism. Mice were injected with allogeneic
      tumor cells transduced with the murine IL-6 gene. Serum IL-6 levels were
      correlated exponentially with tumor weight. Secretion of IL-6 from the developed
      tumors was associated with decreased food consumption, reduced body weight, and
      reduced blood glucose levels. Insulin levels did not change, and 2-deoxyglucose
      uptake was not affected in most tissues examined. A significant increase of 2
      deoxyglucose uptake was measured in the liver. Glycogen content in the liver
      determined 0, 6, 12, and 18 days after tumor inoculation was 42, 23, 12, and 3
      mg/g, respectively. The activity of phosphoenolpyruvate carboxykinase was not
      affected. The activity of glucose-6-phosphatase (G-6-Phase) determined 6, 12, and
      18 days after tumor injection was 84, 70, and 50% of G-6-Pase activity in pair
      fed mice bearing nonsecreting tumors, respectively. G-6-Pase mRNA levels were
      markedly reduced due to inhibition of G-6-Pase gene transcriptional rate.

PMID- 9277379
TI  - Fatty acid oxidation is directly regulated by carbohydrate metabolism during
      exercise.
AB  - We determined whether increased glycolytic flux from hyperglycemia and
      hyperinsulinemia directly reduces fatty acid oxidation during exercise. Fatty
      acid oxidation rates were measured during constant-rate intravenous infusion of
      trace amounts of a long-chain fatty acid ([1-13C]palmitate; Pal) vs. a medium
      chain fatty acid ([1-13C]octanoate; Oct). Six endurance-trained men cycled for 40
      min at 50% of maximal O2 uptake 1) after an overnight fast ("fasting") and 2)
      after ingestion of 1.4 g/kg of glucose at 60 min and again 10 min before exercise
      (Glc). Glc caused hyperinsulinemia, a preexercise blood glucose of 6 mM, and a
      34% reduction in total fat oxidation during exercise due to an approximately
      equal reduction in oxidation of plasma-free fatty acids (FFA) and intramuscular
      triglycerides (all P < 0.05). Oxidation of Pal was significantly reduced during
      Glc compared with fast (i.e., 70.0 +/- 4.1 vs. 86.0 +/- 1.9% of tracer infusion
      rate; P < 0.05). However, Glc had no effect on Oct oxidation, which is apparently
      not limited by mitochondrial transport. Furthermore, Glc reduced plasma FFA
      appearance 36% (P < 0.05), indicating a coordination of effects on adipose tissue
      and muscle. In summary, substrate oxidation during exercise can be regulated by
      increased glycolytic flux that is accompanied by a direct inhibition of long
      chain fatty acid oxidation. These observations indicate that carbohydrate
      availability can directly regulate fat oxidation during exercise.

PMID- 9277380
TI  - Decreased muscle insulin receptor kinase correlates with insulin resistance in
      normoglycemic Pima Indians.
AB  - Defects in insulin receptor tyrosine kinase activity are present in insulin
      resistant non-insulin-dependent diabetes mellitus patients and certain
      nondiabetic individuals, both lean and obese. However, the relationship between
      insulin receptor function, insulin action, and obesity is unclear. To address
      this issue, we have employed a new and highly sensitive enzyme-linked
      immunosorbent assay to measure in vitro insulin-stimulated autophosphorylation of
      immunocaptured muscle insulin receptors in a group of 25 normoglycemic Pima
      Indians. Insulin action, determined during two-step euglycemic insulin clamps,
      varied widely in these subjects. Maximal in vitro insulin stimulation of insulin
      receptor autophosphorylation strongly correlated with both low (Mlow)- and high
      (Mhigh)-dose insulin-stimulated glucose disposal (r = 0.62 and 0.51, P < 0.002
      and 0.011, respectively). Insulin receptor autophosphorylation was inversely
      related to percent body fat (r = -0.52, P < 0.009). After control for percent
      body fat, receptor autophosphorylation remained correlated with Mlow (partial r =
      0.49, P < 0.025). These data therefore suggest that defects in insulin receptor
      function are major contributors to insulin resistance in both lean and obese
      normoglycemic Pima Indians.

PMID- 9277381
TI  - Glucose turnover in humans in the basal state and after intravenous glucose: a
      comparison of two models.
AB  - This study investigated the ability of two models to represent glucose kinetics
      in the basal steady state and during an intravenous glucose tolerance test
      (IVGTT). Six young nonobese male subjects were studied after an overnight fast.
      Two bolus injections of [U-13C]glucose were given 150 min apart, the first
      without and the second together with concomitant injection of unlabeled glucose.
      [3-3H]glucose was constantly infused throughout the study and served to provide
      an independent means for evaluation of system responses. A linear time-invariant
      three-compartmental model and the two-compartment time-variant model proposed by
      Caumo and Cobelli were used to interpret measured time courses of [U-13C]glucose
      and to reconstruct endogenous glucose production and glucose removal. The ability
      of the two models to describe the glucose tracer time course was comparable.
      Simulation studies showed that the two-compartmental time-variant system better
      predicted measured [3-3H]glucose concentration profiles than did the three
      compartmental time-invariant model. However, endogenous glucose production and
      the integral of excess glucose removal over basal during the IVGTT derived from
      the two models were almost identical.

PMID- 9277382
TI  - Effect of acute plasma volume expansion on substrate turnover during prolonged
      low-intensity exercise.
AB  - We investigated the effect of acute, graded increases in plasma volume (PV) by
      use of dextran on substrate turnover and oxidation during exercise. Eight
      untrained males [peak aerobic power (VO2peak) = 45.2 +/- 2.2 (SE) ml.kg-1.min-1]
      performed 2 h of cycle ergometry at 46 +/- 4% of VO2peak on three occasions in a
      randomized order: 0% PV expansion (CON) and after 14% (LOW) and 21% (HIGH) PV
      expansion. Glucose and glycerol turnover were measured using primed continuous
      infusions of [6,6-2H2]glucose and [2H5]glycerol, respectively. Glycerol rate of
      appearance (Ra) was taken as a relative index of whole body lipolysis. Increases
      in PV had no effect on glucose Ra or disappearance (Rd) either at rest or during
      exercise. At the onset of exercise, both glucose Ra and Rd increased
      approximately 100% (P < 0.01). Glucose Ra and Rd continued to increase with
      exercise duration (P < 0.05) so that, at 120 min of exercise, they were > 330%
      higher than at rest (P < 0.01). Glycerol Ra also increased with exercise duration
      (P < 0.05). Total lipolysis during exercise, calculated as the area under the
      glycerol Ra vs. time curve, was reduced during LOW vs. CON (P < 0.01). Further
      expansion of PV (HIGH) had no additional effect on whole body lipolysis. No
      effect of hypervolemia was observed on whole body fat or carbohydrate oxidation.
      These results indicate that acute PV expansion can alter whole body lipolysis,
      possibly via a reduction in catecholamine secretion.

PMID- 9277383
TI  - Insulin-stimulated amino acid utilization during glucose and amino acid clamps
      decreases with development.
AB  - Neonatal animals utilize their dietary amino acids for protein accretion with
      high efficiency, and this efficiency declines during early life. The factors
      responsible for this developmental change are unknown. Our objectives were to
      determine whether amino acid (AA) utilization is stimulated by insulin in the
      neonate and whether this response changes during the suckling period. Two
      hyperinsulinemic-euglycemic clamp infusion studies, using 10-2,000 ng insulin.kg
      0.66.min-1, were performed in 7- and 26-day-old pigs. In study I, no AA were
      provided during the infusion, and the resultant decline in plasma AA levels was
      defined. In study II, plasma AA were clamped at near-fasting levels, and whole
      body utilization of exogenous AA was determined by measuring the rate of infusion
      of an AA mixture necessary to maintain basal plasma lysine concentrations. In
      study I, the half-maximal effective dose (ED50) for the fall in AA concentrations
      with increasing plasma insulin concentration was lower in 7- than in 26-day-old
      pigs, and the nadir in AA concentration was achieved by only 20 microU/ml
      insulin. In study II, the utilization of exogenous AA during hyperinsulinemic
      euglycemic AA clamps exhibited a higher maximum response (Rmax) (49 vs. 26 mumol
      AAtotal.min-1.kg-1) and a lower ED50 (18 vs. 45 microU insulin/ml) in 7- than in
      26-day-old pigs. Plasma urea nitrogen concentrations did not rise with increasing
      insulin and AA infusion rates. These results indicate that insulin stimulates the
      utilization of exogenous AA in neonatal pigs and that both the insulin
      sensitivity and responsiveness of AA utilization decline over the suckling
      period. The infused AA were likely utilized for protein accretion.

PMID- 9277384
TI  - Effects of dexamethasone on hepatic glucose production and fructose metabolism in
      healthy humans.
AB  - This study was designed to determine whether glucocorticoids alter autoregulation
      of glucose production and fructose metabolism. Two protocols with either
      dexamethasone (DEX) or placebo (Placebo) were performed in six healthy men during
      hourly ingestion of[13C]fructose (1.33 mmol.kg-1.h-1) for 3 h. In both protocols,
      endogenous glucose production (EGP) increased by 8 (Placebo) and 7% (DEX) after
      fructose, whereas gluconeogenesis from fructose represented 82 (Placebo) and 72%
      (DEX) of EGP. Fructose oxidation measured from breath 13CO2 was similar in both
      protocols [9.3 +/- 0.7 (Placebo) and 9.6 +/- 0.5 mumol.kg-1.min-1 (DEX)].
      Nonoxidative carbohydrate disposal, calculated as fructose administration rate
      minus net carbohydrate oxidation rate after fructose ingestion measured by
      indirect calorimetry, was also similar in both protocols [5.8 +/- 0.8 (Placebo)
      and 5.9 +/- 2.0 mumol.kg-1.min-1 (DEX)]. We concluded that dexamethasone 1) does
      not alter the autoregulatory process that prevents a fructose-induced increase in
      gluconeogenesis from increasing total glucose production and 2) does not affect
      oxidative and nonoxidative pathways of fructose. This indicates that the insulin
      regulated enzymes involved in these pathways are not affected in a major way by
      dexamethasone.

PMID- 9277385
TI  - Gender differences in energy expended during activities and in daily energy
      expenditure of elderly people.
AB  - Gender effects on energy expended during light seated activities, walking,
      cycling, and sleep and their consequences on daily energy expenditure (EE) were
      examined in 11 men and 15 women aged 66.4 +/- 7.1 yr. Two open-circuit whole body
      calorimeters were used for EE measurements, except for cycling, during which EE
      was measured separately with the use of a face mask. Lean body mass (determined
      using H218O dilution method), fat mass, usual physical activity level, and
      activity intensity (e.g., walking speed and cycling power output) were taken as
      covariates in the analysis of EE variations before studying gender effects.
      Sleeping metabolic rate (SMR) and daily EE, adjusted for differences in all
      covariates, were 11.2 (P = 0.005) and 8.7% (P = 0.071) lower in women than in
      men, respectively. No gender-related differences were found in the various
      physical activity EEs above SMR (e.g., gross EE-SMR) [light seated activities (P
      = 0.790), walking (P = 0.263), and cycling (P = 0.287)] and daily physical
      activity EE above SMR (P = 0.587) after adjustment for differences in all
      covariates. Therefore, the lower adjusted daily EE of women could be related to
      their lower SMR, the most reliable criterion of whole body metabolic rate.

PMID- 9277386
TI  - Involvement of capsaicin-sensitive nerves in regulating the hormone and glucose
      metabolic response to endotoxin.
AB  - This study investigated the role that sensory nerves play in mediating the
      hormone and glucose metabolic response to endotoxin [lipopolysaccharide (LPS)].
      Adult rats were pretreated subcutaneously with capsaicin to selectively destroy
      primary sensory afferent nerve fibers. Ten days later, [3-3H]glucose was infused
      intravenously to assess whole body glucose flux before and after the intravenous
      injection of Escherichia coli LPS (100 micrograms/100 g body wt). Control animals
      responded to LPS with characteristic increases in the plasma concentration of
      glucose (91%) and lactate (threefold) and elevations in the rates of glucose
      appearance and disappearance (77%). In capsaicin-treated rats, the maximal LPS
      induced increase in these parameters was attenuated by 50-60%. In addition, these
      animals were hypoglycemic at the conclusion of the experiment. Control animals
      demonstrated early and sustained elevations in circulating levels of
      corticosterone, glucagon, and catecholamines. In contrast, the early LPS-induced
      elevation in epinephrine and norepinephrine, and to a lesser extent glucagon, was
      completely absent or greatly impaired by capsaicin pretreatment. In a separate
      study, the epinephrine-induced increase in glucose flux was blunted by 75% in
      capsaicin-treated rats. These data indicate that sensory afferent neurons play a
      critical role in the early secretory response of glucagon and catecholamines, the
      maintenance of tissue catecholamine responsiveness, and the stimulation of
      glucose production after LPS.

PMID- 9277387
TI  - Ovine fetal metabolism during norepinephrine infusion.
AB  - Although stress in fetal life not only increases fetal catecholamine
      concentration but also decreases fetal growth, there have been few studies that
      define the specific role of catecholamines in mediating the fetal response to
      stress. None, however, have investigated effects on fetal amino acid or protein
      metabolism, processes that should be affected during aberrant fetal growth.
      Therefore, hormone concentrations as well as oxygen, glucose, lactate, and amino
      nitrogen, leucine, and protein metabolism were measured with and without
      norepinephrine infusion in fetuses of eight pregnant ewes (118-125 days of
      gestation). Transumbilical uptake of oxygen increased during norepinephrine
      infusion, whereas uptake of glucose remained constant and that of lactate and
      amino acids fell. The proportion of fetal oxidative metabolism that could be
      supported by transplacental uptake of exogenous substrates was < 1, indicating
      that endogenous substrates were used to maintain fetal oxidative metabolism and
      therefore that fetal growth was diminished. Both fetal leucine uptake and
      oxidation decreased during norepinephrine infusion, as did fetal protein
      synthesis and proteolysis. Fetal protein synthesis fell more than proteolysis,
      however. Consequently, fetal protein accretion, a variable closely related to
      fetal growth, also fell. Thus the effects of norepinephrine infusion in fetuses
      suggest that fetal catecholamines play an important role not only in altering
      fetal metabolism but also in regulating fetal growth.

PMID- 9277388
TI  - Regulation of glucose production during exercise at 80% of VO2peak in untrained
      humans.
AB  - To determine whether alterations in insulin and/or glucagon secretion play an
      important role in stimulating glucose production (Ra) during intense but
      submaximal exercise, we studied six untrained subjects during 30 min of cycling
      at 80% of peak oxygen uptake on two occasions: once under control conditions and
      once when alterations in insulin and glucagon secretion were prevented with the
      use of the pancreatic islet clamp technique. In the latter experiments, glucose
      was infused during exercise to match glycemia with control levels. Glucose
      kinetics were measured in both trials using a primed, continuous infusion of [6,6
      2H]glucose. In the control trial, glucose Ra rose from 11.9 +/- 0.8 mumol.min
      1.kg-1 at rest to 42.5 +/- 4.3 mumol.min-1.kg-1 by the end of exercise. A similar
      increment was observed in the islet clamp experiments, with endogenous Ra peaking
      at 37.2 +/- 7.9 mumol.min-1.kg-1. This was true even through glucagon
      concentration did not change from basal and insulin concentration actually rose
      (the latter apparently due to a decrease in insulin clearance during intense
      exercise). Thus neither decrements in insulin or increments in glucagon are
      apparently required to stimulate glucose Ra under the present conditions. Because
      epinephrine levels rose only slightly, it appears that either neurally released
      norepinephrine or some other, as yet unidentified, factor is responsible for
      stimulating glucose Ra during intense but submaximal exercise.

PMID- 9277389
TI  - Interaction of corticosterone and gonadal steroids on lipid deposition in the
      female rat.
AB  - The present study was designed to evaluate the interaction of corticosterone
      (CORT) and female gonadal steroids on energy balance and lipid metabolism. To
      this end, a 2 x 4 factorial experiment was carried out in which two cohorts of
      rats differing in their ovary status [OV status: intact (INT) and ovariectomy
      (OVX)] were each divided into four groups defined by their CORT status [CORT
      status: nonadrenalectomized (non-ADX), ADX without CORT replacement (placebo
      subcutaneous pellet), ADX with low-dose CORT replacement, and ADX with high-dose
      CORT replacement]. After 3 wk of treatment and a 12-h fast, rats were killed and
      their carcasses analyzed for energy (lipid and protein) content. In addition,
      indexes of endogenous triglyceride (TRIG) production (liver TRIG content),
      transport into plasma (triglyceridemia), and incorporation into fat stores
      [lipoprotein lipase (LPL) activity in adipose tissue (AT)] were assessed. OV and
      CORT status interacted on body weight gain, total energy, and fat gains. The
      interactions arose from the fact that the twofold increase in these variables
      brought on by OVX was abolished by ADX and restored by CORT replacement. Although
      in ADX groups there was a dose-related restoration of total energy and fat gain
      by CORT replacement in both INT and OVX cohorts, the impact thereupon of OVX
      observed in the non-ADX group reappeared only in ADX animals receiving the high
      dose of CORT. Protein gain was increased by OVX solely in non-ADX rats, whereas
      the high dose of CORT prevented any net protein gain independently of the OV
      status. Consistent with treatment effects on total body fat gain, OVX resulted in
      an increase in liver TRIG content, AT weight, AT LPL activity, and plasma
      insulin. All these effects of OVX were abolished by ADX and restored by the high
      dose of CORT. Plasma TRIG were unaffected by OV status but were highly responsive
      to CORT status. All treatment effects were highly correlated with cumulative food
      intake. This study shows that the presence of CORT is required for OVX to exert
      its action on global energy balance and the concomitant, closely integrated
      adaptations of lipid metabolism.

PMID- 9277390
TI  - Splanchnicotomy increases adrenal sensitivity to ACTH in nonstressed rats.
AB  - Awake rats demonstrate an ultradian rhythm in adrenal secretion of
      corticosterone. Splanchnic denervation in unstressed rats increases the frequency
      of corticosterone pulses, revealing an inhibitory function of adrenal
      innervation. In contrast, one day after surgical stress, adrenal denervation
      reduces adrenal pulsatility, suggesting a stimulatory function of adrenal
      innervation. To test whether neural modulation of pulsatile secretion was due to
      a direct effect of the splanchnic nerve on adrenal sensitivity to
      adrenocorticotropic hormone (ACTH), rats treated with dexamethasone were
      administered repetitive pulses of ACTH, and the amplitude of corticosterone
      responses was determined. Intact or control (C) and splanchnicotomized (SPLNX)
      rats were tested at 2 or 5 days after surgery. Five days after surgery, adrenal
      responsiveness in C animals was reduced compared with SPLNX animals. However, no
      differences were seen 2 days after surgery. To determine whether the reduction in
      adrenal responsiveness involved a cellular or organ level mechanism, dispersed
      adrenal cortical cells isolated from intact or denervated adrenal glands were
      stimulated with ACTH, and corticosterone secretion was determined. Consistent
      with in vivo results, denervation increased the responsiveness of adrenal cells
      obtained 5, but not 1 or 2, days after surgery. These findings support a neurally
      mediated inhibition of adrenal sensitivity to ACTH in unstressed rats.

PMID- 9277391
TI  - Diabetic RBC-induced oxidant stress leads to transendothelial migration of
      monocyte-like HL-60 cells.
AB  - Red blood cells (RBC) from patients with diabetes mellitus exhibit an increased
      propensity to adhere to cultured human umbilical vein endothelial cells (HUVEC)
      as a result of interaction of advanced glycation end products with their counter
      receptors, contributing to the pathogenesis of vascular complications. We
      determined whether the interaction of diabetic RBC with HUVEC induced cellular
      oxidant stress that would culminate in adherence and diapedesis of monocytes,
      these being initiating events in endothelial injury and atherogenesis. We show
      that the adherence of diabetic RBC (2% hematocrit), but not normal RBC, to HUVEC
      results in a fourfold increase in the production of lipid peroxides. Furthermore,
      diabetic RBC-induced oxidant stress causes a sixfold increase in platelet
      endothelial cell adhesion molecule-1 (PECAM-1) phosphorylation and doubles
      transendothelial migration of monocyte-like HL-60 cells; both are blocked by
      antioxidants and protein kinase C (PKC) inhibitors. Our results show that the
      adherence of diabetic RBC to endothelial cells initiates a cascade of cellular
      events resulting in PKC activation, causing PECAM-1 phosphorylation and
      concomitant transendothelial migration of monocytes. The increased diapedesis of
      monocytes, brought about by the interaction of diabetic RBC across vascular
      endothelium, may play an important role in accelerated atherosclerosis and
      cardiovascular disease in diabetics.

PMID- 9277392
TI  - Superoxide dismutase reduces islet microvascular injury induced by streptozotocin
      in the rat.
AB  - Intravenous administration of streptozotocin (STZ) leads to permanent diabetes
      mellitus in rats. We investigated the possible role of islet microcirculatory
      changes and free radical formation in this animal model. In vivo fluorescence
      microscopy was performed for 4 h after administration of STZ. Vascular
      permeability, capillary blood flow, and endothelial leukocyte adhesion were
      measured in endocrine and exocrine pancreatic tissue. The earliest
      microcirculatory event was an increase in vascular permeability in pancreatic
      islets, with a peak 1 h after STZ administration. The difference between islet
      and exocrine tissue light intensity was +15.8 +/- 5.6% at t = 60 min. Islet blood
      flow velocity significantly decreased after 3 h, whereas blood flow in the
      exocrine pancreas was not affected. Complete stasis of islet blood flow was
      observed only in rats receiving STZ. Neither increased leukocyte adhesion to
      islet vascular endothelium nor ischemia-reperfusion phenomena were observed.
      Prophylactic administration of the radical scavenger superoxide dismutase
      prevented STZ-induced damage to the islet microcirculation in the initial phase
      of this model. We conclude that STZ leads to severe microcirculatory disturbances
      within pancreatic islets in rats. Apparently, these changes are mediated at least
      in part by free oxygen radicals.

PMID- 9277393
TI  - Mechanisms of homologous and heterologous desensitization of PTH/PTHrP receptor
      signaling in LLC-PK1 cells.
AB  - Parathyroid hormone (PTH) activates multiple intracellular effectors, including
      adenylyl cyclase (AC) and phospholipase C (PLC), via a single receptor
      [PTH/parathyroid hormone-related protein receptor (PTHR)] expressed in bone and
      kidney. Homologous desensitization of PTHR signaling occurs, but the relative
      importance of reduced receptor expression vs. impaired receptor-effector coupling
      in this process remains unclear. It also is not known if AC and PLC responses to
      PTH are desensitized independently or interdependently. In LLC-PK1 cells that
      expressed transfected wild-type PTHRs, PTH caused dose- and time-dependent
      desensitization of both the AC and PLC-responses to PTH without altering PTHR
      expression. Desensitization of AC was blocked in mutant cells resistant to
      adenosine 3',5'-cyclic monophosphate but not when cells expressed mutant PTHRs
      with defective PLC coupling. Desensitization of PLC was unaffected by PKA
      blockade, partially mimicked by phorbol ester, and not reproduced by agents that
      selectively activated AC. The finding that homologous PTHR desensitization in LLC
      PK1 cells is signal specific suggests that prior exposure of other cells to PTH
      also may induce discordant regulation of subsequent PTHR signaling, altering the
      character as well as the intensity of the hormonal response.

PMID- 9277394
TI  - Moderate exercise at energy balance does not affect 24-h leucine oxidation or
      nitrogen retention in healthy men.
AB  - Short-term metabolic experiments have revealed that physical exercise increases
      the oxidation of leucine, which has been interpreted to indicate an increased
      requirement for dietary protein in physically active subjects. Because it may be
      inaccurate to extrapolate measurements of amino acid oxidation made over a few
      hours to the entire day, we have carried out a continuous 24-h intravenous [1
      13C]leucine/[15N]urea tracer study in eight healthy adult men. Their diet
      supplied 1 g protein.kg-1.day-1, and exercise (mean maximal O2 consumption 46%)
      was for 90 min during the 12-h fast and 12-h fed periods of the day. Subjects
      were adapted to the diet and exercise regimen for 6 days. Then, on day 7, they
      were dressed in the University of Uppsala energy metabolic unit's direct
      calorimeter suit, were connected to an open-hood indirect calorimeter, and
      received the tracers. Exercise increased leucine oxidation by approximately 50
      and 30% over preexercise rates for fast and fed periods, respectively. This
      increase amounted to approximately 4-7% of daily leucine oxidation. Subjects
      remained in body leucine equilibrium (balance -4.6 +/- 10.5 mg.kg-1.day-1; -3.6
      +/- 8.3% of intake; P = not significant from zero balance). Therefore, moderate
      exercise did not cause a significant deterioration in leucine homeostasis at a
      protein intake of 1 g.kg-1.day-1. These findings underscore the importance of
      carrying out precise, continuous, 24-h measurements of whole body leucine
      kinetics; this model should be of value in studies concerning the quantitative
      interactions among physical exercise, energy/protein metabolism, and diet in
      humans.

PMID- 9277395
TI  - Enteral glutamate is the preferential source for mucosal glutathione synthesis in
      fed piglets.
AB  - To measure the source and rate of mucosal glutathione (GSH) synthesis, fed
      piglets (28 days old; 7.7 kg) received a 6-h infusion of intragastric [U
      13C]glutamate (n = 11) either with (n = 5) or without (n = 6) an intragastric
      infusion of [1-13C]glycine (0-6 h) and [1,2-13C2(U-13C)]glycine (3-6 h). Eighty
      four percent of the labeled mucosal GSH-glutamate and 86% of the luminal GSH
      glutamate was 13C5. The tracer-to-tracee ratio of GSH-[U-13C]glutamate was 75% of
      that of mucosal glutamate. Sixty percent of the labeled mucosal glutamate was
      13C1, 13C2, or 13C3, but the tracer-to-tracee ratios of these isotopomers in GSH
      glutamate were not significantly different from zero. After 3 h of infusion, the
      tracer-to-tracee ratio of GSH-[U-13C]glycine was 46%, and after 6 h of infusion
      GSH-[13C1]glycine was 82% of that of mucosal glycine. This suggested that the
      half-life of mucosal GSH was 2.7 +/- 0.1 h. We concluded that, in fed piglets,
      mucosal GSH-glutamate derived largely from the direct metabolism of enteral
      glutamate rather than from glutamate that was metabolized within the mucosa.

PMID- 9277396
TI  - Muscle glycogen synthesis in recovery from intense exercise in humans.
AB  - The present study examined the role of lactate and glucose as substrates for
      glyconeogenesis in muscle in recovery from high-intensity exercise in humans.
      Seven subjects performed approximately 100 min of intense intermittent one-legged
      knee extensor exercise on two occasions: with [high lactate (HL)] and without
      [control (C)] intense arm exercise between the leg exercise bouts, leading to end
      exercise arterial plasma lactate concentrations of 16.0 +/- 1.6 and 9.2 +/- 1.6
      mmol/l, respectively (P < 0.05). At the end of exercise, muscle lactate and
      glycogen were similar in HL and C (20.5 +/- 1.3 vs. 17.3 +/- 2.0 mmol/kg wet wt
      and 48.1 +/- 11.3 vs. 56.3 +/- 8.6 mmol/kg wet wt, respectively). Muscle glycogen
      increased (P < 0.05) during the first 5 min of recovery only in HL, but after 90
      min of recovery the muscle glycogen concentration was the same in C and HL (61.2
      +/- 12.0 vs. 71.5 +/- 10.9 mmol/kg wet wt). Muscle lactate not released to the
      blood could maximally account for 28 (C) and 54% (HL) of the increase in muscle
      glycogen during 90 min of recovery or < 10% of glycogen synthesis after full
      recovery. The total net glucose uptake corresponded to 84 (C) and 57% (HL) of the
      glycogen synthesized. Apparently, muscle glyconeogenesis may occur in humans, but
      the role of lactate as a substrate is minor. Instead, blood glucose appears to be
      the most important precursor for muscle glycogen synthesis after intense
      exercise.

PMID- 9277397
TI  - Relationship of visceral adipose tissue and glucose disposal is independent of
      sex in black NIDDM subjects.
AB  - To determine the interrelationship among insulin action, total or regional
      adiposity, and sex, we measured insulin-mediated glucose disposal by the
      euglycemic insulin clamp and adipose distribution using computed axial tomography
      (22 scans) in 32 black men and 20 black women with non-insulin-dependent diabetes
      mellitus (age 48 +/- 9 and 54 +/- 9 yr, body mass index 26.3 +/- 2.3 and 27.2 +/-
      2.6 kg/m2, respectively). Women had approximately 80% more total and subcutaneous
      fat volume than men (31.8 +/- 8.3 vs. 18.6 +/- 6.1 and 28.5 +/- 7.3 vs. 14.7 +/-
      4.6 liters) and less muscle volume (22.9 +/- 3.7 vs. 35.1 +/- 3.8 liters).
      Visceral fat volume did not differ between men and women (3.49 +/- 1.65 vs. 2.96
      +/- 1.22 liters). Despite these body composition differences, an inverse
      nonlinear relationship existed between glucose disposal and visceral fat
      independent of sex (r = -0.58, P < 0.0001; men r = -0.60 and women r = -0.59; the
      slope and intercept were not different in men and women). Visceral fat explained
      a significant portion (34%) of variance in insulin-mediated glucose disposal,
      whereas total or subcutaneous fat and sex did not. Visceral fat appears to affect
      glucose disposal over a restricted range (up to approximately 2.5 l/m2 body
      surface area.

PMID- 9277398
TI  - Tumor necrosis factor activity of pancreatic islets.
AB  - Tumor necrosis factor (TNF) is involved in the pathogenesis of acute sepsis
      induced organ injury and has been implicated as a mediator of metabolic
      alterations observed during sepsis. Pancreatic islet cell function may be
      significantly compromised during sepsis or endotoxemia, and sepsis also increases
      plasma levels of epinephrine, a modifier of islet insulin secretion. We proposed
      that islets exposed to bacterial lipopolysaccharide (LPS) produce TNF and that
      epinephrine attenuates islet secretory activity. We monitored the effects of LPS
      and epinephrine on TNF and insulin activity of isolated Wistar-Furth rat islets
      (pancreas digested with collagenase, islets isolated using Ficoll gradients; n =
      4 islet populations, each with 632 +/- 11 islets/2.5 ml culture medium). Islets
      were incubated (37 degrees C, 5% CO2) 3 days. LPS (Escherichia coli, 1
      microgram/ml) and epinephrine (14 micrograms/ml) were added to the islets, and
      incubations were continued for 1-4 h. Glucose (Beckman Glucose Analyzer), insulin
      (radioimmunoassay), and TNF (L929 cytotoxicity assay) were measured in the islet
      medium samples at 1- to 4-h time points. In the conditioned medium, glucose
      decreased (P < 0.05), insulin increased (P < 0.05), and exposure to LPS did not
      alter these levels [P = not significant (NS)] but did increase TNF activity by
      400% (P < 0.05). Epinephrine reduced insulin by 38-43% (P < 0.05) and TNF by 20
      25% (P < 0.05) but had no effect on glucose levels (P = NS). We conclude that
      insulin is secreted from isolated islets and that exposure to LPS acutely
      increases islet-derived TNF activity, whereas epinephrine modifies TNF and
      insulin secretion of rat pancreatic islets.

PMID- 9277399
TI  - Simulation of IGF-I pharmacokinetics after infusion of recombinant IGF-I in human
      subjects.
AB  - The pharmacokinetics of recombinant human insulin-like growth factor I (IGF-I)
      were studied in four healthy volunteers by a 3-h infusion at a rate of 20
      micrograms.kg-1.h-1. A compartmental model was used to simulate the plasma "free"
      IGF-I and IGF-I associated with the 50- and 150-kDa plasma protein fractions. The
      model is based on the concept that free IGF-I and IGF binding proteins (IGFBPs)
      are the substrates for their own degradation and that they act as reservoirs for
      retention of IGF-I in the vascular compartment or inhibiting IGF-I action. The
      metabolic clearance rate (MCR) of free IGF-I is estimated as 2.62 +/- 0.94 ml.min
      1.min-1 with a production rate of 4.75 +/- 1.74 mg/day (621.0 +/- 227.34
      nmol/day). The simulation shows that higher concentrations of IGFBP-3 would
      increase the estimate of MCR for free IGF-I by reducing free IGF-I concentration.
      The model will be of value for simulation of dynamic profiles of free IGF-I and
      receptor-bound IGF-I in a variety of pathophysiological conditions.

PMID- 9277400
TI  - Leptin receptors in the adrenal medulla of the rat.
AB  - Leptin is the protein product of the recently cloned obesity gene. Leptin
      receptor mRNA is found in a number of central and peripheral locations. The
      hypothalamus is a presumed site of action. However, little is known about the
      specific locations of the receptor in peripheral organs. Epinephrine has potent
      anorectic effects and can cause weight loss by a variety of mechanisms. Excretion
      of epinephrine is reduced in the ob/ob mouse, which lacks leptin, suggesting an
      effect by leptin on the adrenal medulla. In the current study, the presence of
      the leptin receptor was identified on epinephrine-secreting cells in the adrenal
      medulla. Immunohistochemical studies found dense leptin receptor-like
      immunoreactivity in the adrenal medulla with no labeling in the adrenal cortex.
      Double immunofluorescent labeling confirmed that the leptin receptor was present
      on cells that were phenylethanolamine N-methyltransferase-like immunoreactive and
      therefore were epinephrine-secreting cells. Leptin receptor mRNA in the adrenal
      medulla was detected by reverse transcriptase-polymerase chain reaction, with the
      majority of the mRNA coding for the short isoform (Ob-Ra) of the receptor.
      Finally, autoradiography was performed using 125I-labeled leptin; specific
      binding was found in the adrenal medulla, with no specific binding in the adrenal
      cortex. These results suggest that leptin may have a direct effect on epinephrine
      secreting cells in the adrenal medulla. Epinephrine may play a role in mediating
      the effects of leptin to reduce body weight.

PMID- 9277401
TI  - Epithelial cell growth and differentiation. II. Intestinal apoptosis.

PMID- 9277402
TI  - Intestinal physiology and pathology in gene-targeted mouse models of cystic
      fibrosis.
AB  - Cystic fibrosis (CF) is a fatal genetic disorder that affects approximately 1 in
      2,500 live Caucasian births. The disease can be described as a generalized
      exocrine disease affecting a variety of epithelial tissues, with early
      manifestation as meconium ileus in a significant number of neonates. Cloning of
      the gene causing CF was accomplished in 1989, and the protein product, cystic
      fibrosis transmembrane conductance regulator (CFTR), has been conclusively shown
      to be an adenosine 3',5'-cyclic monophosphate (cAMP)-regulated Cl- channel.
      Subsequently, several mouse models of CF were generated by gene-targeting
      approaches in an attempt to further understand this disease. The initial
      excitement generated by the emergence of these mouse models was somewhat tempered
      by the finding that none of the models developed airway disease, which is
      currently responsible for most of the morbidity and mortality in the human CF
      population. However, the various CF mouse models, of which there are now 10, are
      remarkably similar to their human counterparts with respect to intestinal
      pathophysiology. Most importantly, the intestinal tract of the CF mouse models
      demonstrates the absence of cAMP-mediated Cl- transport, which is a hallmark of
      CF disease. Furthermore, the murine CF intestinal tract also shows an inability
      to secrete HCO3-, defective cAMP regulation of electroneutral NaCl absorption,
      and elevated electrogenic Na+ transport in the distal colon, as well as other ion
      transport perturbations. Besides the fundamental mechanisms of ion transport
      studied in the murine CF intestinal tract, these models have also been important
      in understanding other tissues with regard to CF. Mice heterozygous for the CFTR
      knockout gene have a reduced ability to secret Cl- and fluid and therefore
      provide further support for the CF "heterozygote advantage" hypothesis. Some CF
      mouse models maintain a limited ability to secrete Cl-, which may be due to
      accessory genes that are hypothesized to ameliorate disease severity in the
      intestines of these mice. This review describes the CF models generated and
      compares the murine defects in ion transport with observed abnormalities in the
      human CF intestine.

PMID- 9277403
TI  - Expression cloning of NaDC-2, an intestinal Na(+)- or Li(+)-dependent
      dicarboxylate transporter.
AB  - A cDNA coding for a Na(+)-dicarboxylate cotransporter from Xenopus laevis
      intestine, NaDC-2, was isolated by functional expression cloning in Xenopus
      oocytes. NaDC-2 encodes a 622-residue polypeptide with a predicted mass of 68.6
      kDa. The sequence and secondary structure of NaDC-2 are related to the mammalian
      renal Na(+)-dicarboxylate and Na(+)-sulfate cotransporters. NaDC-2 mRNA is
      expressed only in the intestine. Oocytes injected with NaDC-2 cRNA exhibit
      increased transport of succinate, citrate, and glutarate. Transport of succinate
      by NaDC-2 is stimulated by Na+ or Li+, with Michaelis-Menten constant values for
      succinate of 0.3 mM (in Na+) and 0.7 mM (in Li+). Na+ and Li+ activation curves
      show sigmoid kinetics, with Hill coefficients of 1.4 (nNa) and 1.7 (nLi),
      indicating that multiple cations are involved in the transport of succinate. The
      transport of succinate by NaDC-2 is insensitive to pH, whereas the transport of
      citrate is inhibited at high pH. The differences in functional properties between
      NaDC-2 and the structurally related Na(+)-dicarboxylate cotransporters NaDC-1 and
      hNaDC-1 will form the basis of detailed structure-function studies.

PMID- 9277404
TI  - Intracellular iron regulates iron absorption and IRP activity in intestinal
      epithelial (Caco-2) cells.
AB  - In vertebrates, body Fe homeostasis is maintained through the regulation of its
      intestinal absorption. In addition, because Fe is both essential and toxic,
      intracellular Fe levels are tightly regulated. Consequently, intestinal
      epithelial cells are in the unique position of being responsible simultaneously
      for the regulation of body Fe absorption and the regulation of their
      intracellular Fe levels to remain viable. We tested the hypothesis that the
      regulation of transepithelial Fe transport and the regulation of intracellular Fe
      levels are sensitive to a common effector. To this end, we used a recently
      developed protocol to obtain cultured intestinal epithelial cells with defined
      intracellular Fe concentrations. In these cells we tested Fe absorption and Fe
      regulatory protein (IRP) activities. We found that transepithelial Fe transport
      was inversely related to 20-200 microM intracellular Fe and that Caco-2 cells
      expressed Fe regulatory protein-1 and Fe regulatory protein-2 activities. Fe
      regulatory protein-1 activity, Fe regulatory protein-2 mass, transferrin receptor
      density, and ferritin levels were regulated by intracellular Fe in the same range
      (20-200 microM) that affected transepithelial Fe transport. These results suggest
      that a common Fe-responsive factor regulates both intracellular Fe levels and Fe
      absorption by Caco-2 cells.

PMID- 9277406
TI  - Fatty acid regulation of fatty acid-binding protein expression in the small
      intestine.
AB  - The effects of dietary oil intake and fatty acid infusions on the expression of
      intestinal and liver fatty acid-binding proteins (I-FABP and L-FABP,
      respectively) were investigated in the small intestine of mice. A daily force
      feeding for 7 days with 0.2 ml sunflower oil specifically increased L-FABP mRNA
      and protein levels in duodenum and proximal jejunum. This upregulation was
      mediated in time- and dose-dependent manners by a minute quantity of linoleic
      acid, the main fatty acid found in sunflower oil. The L-FABP induction was only
      found with long-chain fatty acids, with the nonmetabolizable, substituted fatty
      acid alpha-bromopalmitate being far more active. A hormonally mediated effect is
      unlikely because long-chain fatty acids induced L-FABP mRNA in the Caco-2 cell
      line cultured in serum-free medium. Therefore, long-chain fatty acids are strong
      inducers of L-FABP gene expression in the small intestine. In contrast to data
      found in the rat, I-FABP gene expression appears to be unaffected by a lipid
      enriched diet in the mouse.

PMID- 9277405
TI  - L-type calcium channels regulate gastrin release from human antral G cells.
AB  - In mRNA samples isolated from a gastrin (G) cell-enriched human antral cell
      preparation, reverse transcription-polymerase chain reaction identified products
      encoding part of the alpha 1-subunit of class C and D L-type voltage-dependent
      Ca2+ channels (VDCCs). Analysis of the polymerase chain reaction products
      demonstrated a 100% homology with the known human gene sequences. An antibody to
      the class D alpha 1-subunit immunostained 30-40% of the cultured cells; of these
      90% were gastrin immunoreactive. Gastrin release stimulated by terbutaline (beta
      2-agonist) and forskolin was abolished by blockade of L-type VDCCs; the effect of
      3.6 mM extracellular Ca2+ was only partially reversed. In G cells the rise in
      intracellular Ca2+ observed in response to increasing extracellular Ca2+ from 0.5
      to 3.6 mM was reduced by nitrendipine. These results indicated that human antral
      cells expressed class C and D L-type VDCCs. Activation of G cells with beta
      adrenergic agonists required an influx of extracellular Ca2+ through these
      channels to stimulate gastrin release. However, activation of L-type channels was
      not the only mechanism underlying Ca(2+)-stimulated gastrin release.

PMID- 9277407
TI  - Biosynthesis of mucins (MUC2-6) along the longitudinal axis of the human
      gastrointestinal tract.
AB  - Little is known about the biosynthesis of mucin molecules in humans. Our aim was
      to examine the mucin biosynthesis (MUC2-6) along the longitudinal axis of the
      healthy human gastrointestinal tract. Biopsies of human stomach and small and
      large intestine were metabolically labeled with 35S-labeled amino acids,
      [35S]sulfate, or[3H]galactose, immunoprecipitated with antibodies against MUC2-6,
      and analyzed by reducing sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE), MUC5AC [apparent molecular weight (M(r)) 500,000] and
      MUC6 (apparent M(r) 400,000) were detected in the stomach but not in the small or
      large intestine, MUC3 (apparent M(r) 550,000) was detected in duodenum and
      jejunum, MUC2 (apparent M(r)600,000) was detected throughout the small and large
      intestine, and MUC4 (apparent M(r) > 900,000) was detected predominantly in the
      large intestine. Interestingly, some individuals displayed double bands of MUC2
      and MUC3 precursors, suggesting allelic variation within the respective genes.
      Between small and large intestine mature secreted MUC2 showed differences in
      mobility on SDS-PAGE, suggesting differences in glycosylation. Each of the MUC2,
      MUC3, MUC4, MUC5AC, and MUC6 precursors could be distinguished
      electrophoretically, and each showed region-specific expression along the
      gastrointestinal tract.

PMID- 9277408
TI  - Role of kinases and phosphatases in the regulation of fluid secretion and Cl
      /HCO3- exchange in cholangiocytes.
AB  - The role of protein kinase A (PKA), protein kinase C (PKC), and protein
      phosphatases in the process of secretin stimulation of fluid and bicarbonate
      secretion from biliary epithelium was examined using a novel isolated bile duct
      unit (IBDU) model from rat liver. Sp-adenosine 3',5'-cyclic monophosphothiolate
      (Sp-cAMPS), 100 microM, a PKA-specific agonist, significantly increased secretion
      during a 30-min perfusion (+61%, P < 0.01). In contrast, preincubation and
      perfusion of Rp-cAMPS, 100 microM, a specific PKA inhibitor, reduced the ability
      of secretin to stimulate both fluid secretion (111 vs. 25%; P < 0.01) and Cl
      /HCO3- exchanger activity (80 vs. 28%). Neither the PKC agonist phorbol 12
      myristate 13-acetate, 10 microM, nor the PKC antagonist staurosporine showed any
      effect on either basal or secretin-stimulated fluid secretion or Cl-/HCO3-
      exchange activity in IBDU. Okadaic acid, a specific inhibitor of protein
      phosphatases 1 and 2A, also had no effect on basal fluid secretion or on the
      basal activity of the Cl-/HCO3- exchanger. However, okadaic acid resulted in
      persistence of secretion after removal of secretin, in contrast to the reduction
      in secretion observed in controls. These findings indicate that PKA but not PKC
      is involved in the signal transduction of secretin-stimulated fluid secretion and
      Cl-/HCO3- exchange activity in rat bile duct epithelium, a process inactivated by
      dephosphorylation by protein phosphatases 1 and/or 2A.

PMID- 9277409
TI  - Gut ischemia and mesenteric synthesis of inflammatory cytokines after hemorrhagic
      or endotoxic shock.
AB  - The intestine plays a major role in the pathophysiology of multiorgan failure.
      Although the systemic inflammatory response might be induced by endotoxin
      released through bacterial translocation, other factors such as intestinal
      ischemia might be implicated. We investigated the relationship between intestinal
      ischemia-reperfusion and cytokine release in rat models of hemorrhagic or
      endotoxic shock. Plasma levels of tumor necrosis factor-alpha (TNF-alpha),
      interleukin-6 (IL-6), lactate, and endotoxin, as well as macrophage TNF-alpha and
      IL-6 mRNA expression, were assessed at the end of shock and resuscitation.
      Hemodynamic changes and lactate levels suggested the presence of intestinal
      ischemia in both models. Mesenteric levels of TNF-alpha and IL-6 were increased
      by hemorrhage and further increased after saline resuscitation. Similar results
      were obtained with mRNA cytokine gene expression in macrophages. Endotoxin was
      not detectable in the hemorrhagic group. Endotoxic shock also increased
      production of cytokines, which, in contrast to hemorrhage, was not further
      increased by resuscitation. These results suggest that intestinal ischemia
      reperfusion upon hemorrhage and resuscitation may be a major trigger for cytokine
      gene expression in the absence of endotoxin.

PMID- 9277411
TI  - IL-11 inhibits Clostridium difficile toxin A enterotoxicity in rat ileum.
AB  - Interleukin-11 (IL-11) is a stromal cell-derived cytokine with several biological
      activities against hematopoietic cells. Recent results indicated that IL-11
      reduced mucosal damage in animal models of colitis. This study aimed to explore
      the action of recombinant human IL-11 (rhIL-11) on the intestinal effects of
      Clostridium difficile toxin A, an inflammatory enterotoxin, and cholera toxin, a
      noninflammatory enterotoxin in rat ileum. We administered rhIL-11 subcutaneously
      to rats before injection of toxin A into ileal loops and measured fluid
      secretion, epithelial permeability to mannitol, histopathological damage, and
      release of rat mast cell protease II (RMCP II) from intestinal mast cells and of
      tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2
      (MIP-2) from lamina propria macrophages. rhIL-11 (50-1,000 micrograms/kg)
      inhibited toxin A but not cholera toxin-mediated secretion and permeability in a
      dose-dependent fashion and reduced toxin A-induced epithelial cell damage. Rats
      treated with rhIL-11 also showed reduced RMCP II, TNF-alpha, and MIP-2 release in
      response to toxin A. Exposure of rat peripheral monocytes in vitro to rhIL-11 (1
      microgram/ml) inhibited lipopolysaccharide and toxin A-mediated increases in TNF
      alpha mRNA and protein levels. We conclude that rhIL-11 blocks the intestinal
      effects of C. difficile toxin A, possibly by inhibiting release of inflammatory
      mediators from mucosal mast cells and intestinal macrophages.

PMID- 9277410
TI  - Human hepatocytes express an array of proinflammatory cytokines after agonist
      stimulation or bacterial invasion.
AB  - Inflammatory cells infiltrate the liver in response to microbial infection or
      hepatic injury. To assess the potential role hepatocytes may play in initiating
      or amplifying the acute inflammatory response in the liver, we used three human
      hepatocyte cell lines and primary human hepatocyte cultures to characterize the
      repertoire of cytokines that can be expressed and regulated in hepatocytes in
      response to agonist stimulation or bacterial infection. As reported herein, a
      proinflammatory cytokine gene program that includes C-X-C and C-C chemokines
      [interleukin-8(IL-8), growth related (GRO)-alpha, GRO-beta, GRO-gamma, epithelial
      neutrophil activating peptide-78 (ENA-78), and RANTES] and the cytokines tumor
      necrosis factor-alpha (TNF-alpha) and macrophage colony stimulating factor was
      upregulated in human hepatocytes after stimulation with IL-1 alpha or TNF-alpha
      or bacterial invasion. In contrast, expression of hematopoietic/ lymphoid growth
      factors by the same cells was either down-regulated (erythropoietin and stem cell
      factor) or unchanged (IL-7 and IL-15) in response to the identical stimuli.
      Hepatocytes did not express cytokines that often are associated with the
      regulation of antigen-specific immune responses (IL-2, IL-4, IL-5, IL-10, IL
      12p40, IL-13, and interferon-gamma) or genes for several other proinflammatory
      cytokines [IL-1 alpha, IL-6, monocyte chemotactic protein-1 (MCP-1), and MCP-3]
      or hematopoietic growth factors (granulocyte colony stimulating factor,
      granulocyte macrophage colony stimulating factor, IL-3, and IL-11). Together,
      these studies suggest that hepatocytes can both initiate and amplify acute
      inflammatory responses in the liver through the regulated expression and
      secretion of a specific array of proinflammatory cytokines.

PMID- 9277412
TI  - Exogenous xanthine promotes neutrophil adherence to cultured endothelial cells.
AB  - Oxidants generated by endothelial xanthine oxidase (XO) can help trigger free
      radical-mediated tissue injury. An important event in oxidant-mediated tissue
      injury is neutrophil-endothelial adhesion. Although activation of endothelial XO
      increases adhesion, little is known about xanthine in the adhesive effect of XO.
      This study examined administered xanthine on the adhesion of neutrophils.
      Endothelial [human umbilical vein endothelial cells (HUVEC)] monolayers were
      exposed to xanthine (15 min), and neutrophils were allowed to adhere to HUVEC in
      an adhesion assay. Adhesion was dose dependently increased by xanthine (3-100
      microM). Either catalase (1,000 U/ml), oxypurinol (XO inhibitor; 100 microM), or
      platelet-activating factor (PAF) receptor antagonist (WEB 2086; 10 microM)
      reduced neutrophil adhesion. Superoxide dismutase (1,000 U/ml) had no effect.
      Pretreatment of HUVEC with 50 microM tungsten also blocked xanthine-induced
      adherence. Adhesion was also inhibited by preincubation with 100 U/ml heparin.
      Finally, anti-P-selectin antibody (PB1.3; 20 micrograms/ml) attenuated adhesion.
      Our results indicate that xanthine may promote neutrophil-endothelial adhesion
      via a hydrogen peroxide- and PAF-mediated P-selectin expression.

PMID- 9277413
TI  - Trefoil peptide expression and secretion is regulated by neuropeptides and
      acetylcholine.
AB  - Trefoil peptides are a family of small proteins expressed by goblet cells that
      are secreted onto the apical gastrointestinal mucosal surface, where they are
      present in high concentrations. These peptides appear to both protect the
      epithelium and promote healing after injury. However, the factors regulating the
      expression and secretion of these proteins contributing to mucosal defense have
      not been characterized. To determine the mechanisms controlling production of
      trefoil peptides, the human colon cancer-derived model cell line HT-29 was
      exposed to a variety of potential secretagogues. Expression and secretion of
      human intestinal trefoil factor (hITF) as well as the intestinal apomucin MUC2
      were assessed by Northern and Western blot analysis. Carbachol, an analog of
      acetylcholine, and the neuroendocrine peptides somatostatin and vasoactive
      intestinal polypeptide (VIP) stimulated increased expression of hITF mRNA within
      5 min. These same factors stimulated parallel secretion of the hITF peptide, with
      maximal stimulation observed at concentrations ranging from 10(-6) M (carbachol
      and somatostatin) to 10(-7) M (VIP). Expression and secretion of hITF in response
      to carbachol, VIP, and somatostatin was independent of production of apomucin.
      hITF was not regulated by other neuroendocrine transmitters including histamine
      and substance P. Similarly, hITF expression and secretion was not modulated by
      peptide growth factors (epidermal growth factor, transforming growth factor-beta,
      and keratinocyte growth factor), cytokines [interleukin (IL)-1 beta, IL-2, IL-7,
      and IL-11], or arachidonic acid metabolites (prostaglandin E1/E2 and leukotriene
      B4). In conclusion, trefoil peptides appear to be integrated into mechanisms of
      mucosal defense and repair through the enteric neuroendocrine system and
      independent of the classical mucosal immune cytokine network.

PMID- 9277414
TI  - Dietary diosgenin attenuates subacute intestinal inflammation associated with
      indomethacin in rats.
AB  - We investigated the effects of dietary diosgenin (Dio), a plant-derived
      sapogenin, on indomethacin (Indo)-induced intestinal inflammation and alterations
      in bile secretion in rats. In anesthetized rats, bile secretion, intestinal
      inflammation, and blood chemistry were assessed 3 days after two subcutaneous
      injections of Indo given 24 h apart. Dio (> 80 mg.kg-1.day-1) pretreatment
      significantly inhibited weight and food intake decreases and intestinal
      inflammation. This protective effect was confirmed by examination of gross and
      histological findings and intestinal myeloperoxidase activity. Dio significantly
      increased biliary cholesterol (Chol) output and prevented the decreases in bile
      flow, bile acid output, and biliary alpha-muricholic acid and the increases in
      biliary hyodeoxycholic acid, deoxycholic acid, and hydrophobicity index of bile.
      Significantly more biliary Chol and phospholipids were present in macromolecules
      separate from bile acids and Indo in Dio-treated rats. Dio significantly
      increased the elimination constant of Indo and reduced plasma Indo levels at 3
      and 12 h but did not influence biliary secretion of Indo for 3.5 h after
      injection. Although Dio dose-dependently attenuated subacute intestinal
      inflammation and normalized bile secretion in this model, it may also compromise
      the anti-inflammatory action of indo.

PMID- 9277415
TI  - Protective action of gastrin-17 against alcohol-induced gastric injury in the
      rat: role in mucosal defense.
AB  - Exogenous cholecystokinin (CCK) or exposure of the stomach to the mild irritant
      25% ethanol can prevent gastric injury. Ingestion of ethanol also elicits the
      release of CCK as well as gastrin, which is structurally similar to CCK. This
      study was undertaken in conscious rats to examine the gastroprotective actions of
      gastrin and to assess the effect of CCK-gastrin receptor blockade on adaptive
      cytoprotection with ethanol as the mild irritant. Intravenous (1-25 pmol/kg)
      administration of gastrin-17 dose dependently increased gastric mucosal blood
      flow (laser Doppler) and reduced gastric injury caused by 1 ml of orally
      administered acidified ethanol (150 mM HCl-50% ethanol). Similar gastroprotection
      was achieved with the gastrin secretagogue 5% peptone (1 ml orogastrically). The
      gastroprotective capabilities of gastrin-17 were attenuated by the type B CCK
      (gastrin) receptor antagonist L-365,260 (12.5-25 mg/kg i.p.) and by capsaicin
      desensitization (125 mg/kg s.c.). CCK octapeptide (5 nmol/kg i.v.)-induced
      protection was reversed by the type A CCK receptor antagonist MK-329 (1 mg/kg
      i.p.). Neither receptor antagonist, alone or in combination, reversed the
      protective effects of the mild irritant 25% ethanol (1 ml orogastrically). Thus,
      whereas gastrin may play a role in gastric mucosal defense, neither CCK nor
      gastrin appears to participate in the phenomenon of adaptive cytoprotection.

PMID- 9277416
TI  - Regulation of gastric and pancreatic lipase secretion by CCK and cholinergic
      mechanisms in humans.
AB  - Gastric lipase (HGL) contributes significantly to fat digestion. However, little
      is known about its neurohormonal regulation in humans. We studied the role of CCK
      and cholinergic mechanisms in the postprandial regulation of HGL and pancreatic
      lipase (HPL) secretion in six healthy subjects. Gastric emptying of a mixed meal
      and outputs of HGL, pepsin, acid, and HPL were determined with a double-indicator
      technique. Three experiments were performed in random order: intravenous infusion
      of 1) placebo, 2) low-dose atropine (5 micrograms.kg-.h-1), and 3) the CCK-A
      receptor antagonist loxiglumide (22 mumol.kg-.h-1). Atropine decreased
      postprandial outputs of HGL, pepsin, gastric acid, and HPL (P < 0.03) while
      slowing gastric emptying (P < 0.05). Loxiglumide markedly increased the secretion
      of HGL, pepsin, and acid while distinctly reducing HPL outputs and accelerating
      gastric emptying (P < 0.03). Plasma CCK and gastrin levels increased during
      loxiglumide infusion (P < 0.03). Atropine enhanced gastrin but not CCK release.
      Postprandial HGL, pepsin, and acid secretion are under positive cholinergic but
      negative CCK control, whereas HPL is stimulated by cholinergic and CCK
      mechanisms. We conclude that CCK and cholinergic mechanisms have an important
      role in the coordination of HGL and HPL secretion to optimize digestion of
      dietary lipids in humans.

PMID- 9277417
TI  - CCK-8 infusion increases plasma LMW alkaline phosphatase coincident with
      enterohepatic circulation of bile acids.
AB  - Bile acids may facilitate the release of liver alkaline phosphatase (ALP) from
      its hydrophobic membrane anchor. The purpose of this study was to determine
      whether such a facilitatory role could be observed during the enterohepatic
      circulation of bile acids in dogs. Increased hepatic ALP activity was induced in
      four dogs by daily injections of 4 mg.kg-1.day-1 of prednisone for 10 days.
      Intravenous infusions of cholecystokinin octapeptide (CCK-8) were given before
      treatment and on treatment days 3, 5, 7, and 10 to induce gallbladder emptying
      and the enterohepatic circulation of bile acids. Blood samples were taken hourly
      for 4 h before and for 4 h after CCK-8 infusion. These showed that plasma ALP
      activity increased significantly only after CCK-8 infusion. Gel exclusion
      chromatography, polyacrylamide gel electrophoresis, and octyl Sepharose phase
      separation showed that the increased ALP activity was a hydrophilic, low
      molecular-weight (LMW) isoform, which is consistent with phospholipase release.
      Histochemical staining of endogenous ALP activity showed increased ALP activity
      over sinusoidal surfaces of prednisone-treated dogs. There was also an increased
      serum-to-tissue ratio of ALP activity in the prednisone-treated dogs, suggestive
      of increased release of ALP into blood. It was concluded that bile acids probably
      play a facilitatory role in the enzymatic release of ALP from the sinusoidal
      surface of hepatocytes, which may be accentuated by the presence of increased
      amounts of ALP on the sinusoidal surface in some disease states.

PMID- 9277418
TI  - Increased expression of EGFR in gastric mucosa of aged rats.
AB  - Although in Fischer-344 rats aging is found to be associated with increased
      gastric mucosal proliferative activity, little is known about the intracellular
      events that regulate this process. The present investigation examines the age
      related changes in gastric mucosal tyrosine kinase activity and expression of
      epidermal growth factor receptor(EGFR) and its structural and functional analog
      p185c-erbB-2, the protein product of c-erbB-2/c-neu protooncogene. We observed a
      significantly higher intrinsic tyrosine kinase activity and tyrosine
      phosphorylation of EGFR and p185c-erbB-2 in the gastric mucosa of 24-mo-old
      (aged) rats than in that of their 4- or 12-mo-old counterparts. This was
      associated with increased levels of EGFR protein and steady-state mRNA levels of
      EGFR and p185c-erbB-2. In addition, we also observed threefold higher steady
      state mRNA levels of transforming growth factor-alpha (TGF-alpha; one of the
      primary ligands of EGFR) in the gastric mucosa of aged rats than in that of 4-mo
      old (young) animals. This was accompanied by a fivefold increase in the relative
      concentration of the 18-kDa precursor form of TGF-alpha in gastric mucosal
      membranes but not in the cytosol. In conclusion, our data demonstrate that aging
      is associated with increased tyrosine kinase activity of EGFR and p185c-erbB-2 in
      the gastric mucosa. Moreover, the observation that aging results in increased
      accumulation of TGF-alpha in gastric mucosal membranes raises the possibility
      that the membrane-bound TGF-alpha could partly be responsible for the
      constitutively active EGFR-induced signaling pathway in the gastric mucosa of
      aged rats and, in turn, for stimulation of mucosal proliferative activity.

PMID- 9277419
TI  - Inhibition of sham feeding-stimulated acid secretion in dogs by
      immunoneutralization of gastrin.
AB  - A monoclonal antibody to gastrin was used to study the role of circulating
      gastrin in mediating acid secretion stimulated by sham feeding in dogs. On
      separate days, four conscious, fasted, adult mongrel dogs with esophageal and
      gastric fistulae were pretreated intravenously with either 7 mg of gastrin
      monoclonal antibody (MAb 28.2), 7 mg of keyhole limpet hemocyanin monoclonal
      antibody as control, or 12.5 micrograms/kg atropine sulfate. Thirty minutes
      later, acid secretion was stimulated first by sham feeding for 5 min, then, 60
      min later, by an intravenous infusion of a maximum stimulatory dose of histamine
      (40 micrograms/kg) for 60 min, and after returning to basal, by intravenous
      infusion of a submaximal stimulatory dose of gastrin (200 pmol.kg-1.h-1) for 60
      min. Acid output from secretions collected every 15 min by gravity drainage was
      determined by titration to pH 7.0 with 0.2 N NaOH. Sham feeding-stimulated acid
      output (17.7 +/- 5.5 mmol/h) was significantly inhibited by administration of
      either MAb 28.2 (0 mmol/h) or atropine (1.7 +/- 1.1 mmol/h). Histamine-stimulated
      acid output (19.6 +/- 3.4 mmol/h) was not reduced by either pretreatment. Gastrin
      stimulated acid output (3.9 +/- 0.6 mmol/h) was significantly reduced only by
      pretreatment with MAb 28.2 (0.1 +/- 0.1 mmol/h) and not by atropine (2.2 +/- 1.4
      mmol/h). A background intravenous infusion of pentagastrin (0.5 microgram.kg-1.h
      1) restored sham feeding-stimulated acid output blocked by administration of MAb
      28.2, although the intrinsic acid response to sham feeding could not be seen with
      the background pentagastrin infusion. Furthermore, the plasma gastrin response to
      sham feeding was not blocked by atropine pretreatment. Because
      immunoneutralization of both gastrin and cholinergic blockade significantly
      inhibited acid output during sham feeding, circulating gastrin and cholinergic
      pathways are involved in mediating the cephalic phase of gastric acid secretion
      in dogs.

PMID- 9277420
TI  - Motilin and OHM-11526 activate a calcium current in human and canine jejunal
      circular smooth muscle.
AB  - Motilin is a potent agonist for gastrointestinal smooth muscle contraction and
      has been proposed to regulate the onset of phase III of the migrating motor
      complex in dogs and humans. The effects of motilin and OHM-11526, a motilin
      antagonist in rabbit smooth muscle strips, were examined in isolated canine and
      human jejunal circular smooth muscle cells using whole cell patch-clamp
      techniques with Ba2+ as the charge carrier. Effects of both drugs on inward
      current through L-type Ca2+ channels (ICaL) in both canine and human cells were
      first observed at 10(-3) M. At 10(-6) M, motilin increased ICaL in canine and
      human jejunal circular smooth muscle cells by 43 +/- 20 and 45 +/- 11%,
      respectively, and OHM-11526 increased ICaL by 54 +/- 8 and 54 +/- 14%,
      respectively. The increase in inward current was blocked by nifedipine and by
      guanosine 5'-O-(2-thiodiphosphate) but not by pertussis toxin. Washout of both
      drugs resulted in a further increase in ICaL. These data suggest that both
      motilin and OHM-11526 activate and ICaL in human and canine jejunal circular
      smooth muscle cells through a G protein-coupled mechanism.

PMID- 9277421
TI  - Chronic rejection causes early destruction of the intrinsic nervous system in rat
      intestinal transplants.
AB  - Chronic rejection is the major cause of late intestinal allograft dysfunction. We
      have previously shown that chronic rejection alters the muscularis externa of the
      graft. This study determined structural and functional changes to the enteric
      nerves during chronic rejection. Chronic rejection was achieved in orthotopic
      intestinal transplants (ACI to Lewis) by limited immunosuppression. Syngeneic
      transplants (ACI to ACI) and unoperated ACI rats served as controls. Animals were
      clinically healthy and showed no significant alterations in the mucosal
      architecture on postoperative day 90. Staining for NADPH diaphorase activity
      (nitric oxide synthase-containing neurons) and with neurofilament antibody RT-97
      revealed that chronic rejection decreased the number of jejunal myenteric ganglia
      by approximately 50%. Inhibitory junction potentials (IJPs) to circular muscle
      cells were determined by electrical field stimulation (EFS). In controls and
      syngeneic grafts, EFS caused a stimulus-dependent increase in IJP amplitude, with
      a maximal amplitude of 9 +/- 0.4 and 10 +/- 0.8 mV, respectively. Chronic
      rejection in allografts markedly increased the threshold for IJP initiation and
      decreased the maximal IJP amplitude (5 +/- 0.8 mV). Our data indicate that
      chronic rejection severely damages the muscularis and the enteric nervous system
      before mucosal changes become evident.

PMID- 9277422
TI  - Analysis of the responses of myenteric neurons in the small intestine to chemical
      stimulation of the mucosa.
AB  - Responses of myenteric AH and S neurons to local application of chemicals to the
      mucosa of the guinea pig small intestine were obtained using conventional
      intracellular recording techniques. Preparations were dissected to reveal the
      myenteric plexus over one-half of the circumference of the gut with intact mucosa
      on the the half. Neurons were impaled within the exposed one-half, whereas
      potential stimulants, in buffered saline, were transiently applied to the mucosa,
      1-1.5 mm circumferential from the impalement. The stimulants elicited action
      potentials (AP) in AH neurons that did not arise from synaptic activity. AH
      neurons also responded with slow excitatory postsynaptic potentials (EPSP). S
      neurons were activated synaptically, via fast and slow EPSP, but not
      nonsynaptically. Mucosal application of solutions of a low pH (3-5) or a high pH
      (9-11) were both effective stimulants. Solutions of a neutral pH, which was also
      a control for mild mechanical stimulation, were usually ineffective. Both a short
      chain fatty acid, acetate (pH 7.2), and 5-hydroxytryptamine elicited responses in
      each neuronal type. We conclude that myenteric AH neurons of the guinea pig
      distal ileum are primary afferent neurons that respond to a variety of mucosally
      applied chemical stimuli with burst of AP. In addition, the physiologically
      evoked transmission of slow EPSP to AH neurons suggests that primary afferent
      neurons interconnect in a self-reinforcing network. S neurons are second or
      higher order neurons in the reflex pathways.

PMID- 9277423
TI  - PACAP-(1-38) as neurotransmitter in pig pancreas: receptor activation revealed by
      the antagonist PACAP-(6-38).
AB  - The pituitary adenylyl cyclase-activating polypeptide PACAP-(1-38) has potent
      pancreatic secretory effects. We studied its immunohistochemical localization,
      release, and contribution to secretion induced by electrical vagus stimulation
      using isolated perfused porcine pancreas and the PACAP receptor antagonist PACAP
      (6-38) (10(-7) M). PACAP was found in nerve fibers throughout the pancreas but,
      in particular, encircling ganglionic vasoactive intestinal polypeptide (VIP)
      positive nerve cell bodies and, mostly, colocalized with VIP. Vagus stimulation
      caused its release. PACAP-(1-38)(4 x 10(-9) M) stimulated exocrine and endocrine
      secretion and released VIP. PACAP-(6-38) decreased PACAP-induced flow of juice to
      59 +/- 7.8% and insulin secretion and VIP release to 12 +/- 6.8 and 57 +/- 13%,
      respectively. Glucagon secretion was unaffected. PACAP-(6-38) reduced vagus
      stimulated flow rate to 63 +/- 7.6%, insulin and glucagon responses to 31.8 +/-
      13 and 6 +/- 4%, respectively, and VIP release to 23 +/- 8.4% and reduced VIP
      induced (2 x 10(-9) M) juice and insulin (but not glucagon) outputs to 8.3 +/-
      4.2 and 67 +/- 14%, respectively. In conclusion, 1) pancreatic PACAP fibers seem
      to activate intrapancreatic VIPergic neurons, 2) PACAP-(6-38) antagonism
      documents the role of VIP/PACAP for neural regulation but cannot distinguish
      their relative importance, and 3) a PACAP receptor with low affinity for PACAP-(6
      38), associated with glucagon cells, may exist.

PMID- 9277424
TI  - Role of sensory afferents in the myoelectric response to acute enteric
      inflammation in the rabbit.
AB  - The role of sensory afferents in inflammation-induced alterations in myoelectric
      activity in vivo was investigated in the rabbit small intestine. Isolated ileal
      loops were implanted with serosal electrodes and exposed to ricin or vehicle
      after pretreatment with 125 mg/kg of subcutaneous (125 mg over 3 days) or
      intraluminal (640 microM) capsaicin. After 5 h of myoelectric recording, the
      loops were prepared for histology and for ex vivo generation of eicosanoids.
      Capsaicin exacerbated mucosal damage after exposure to ricin but did not alter
      neutrophil infiltration. Subcutaneous capsaicin alone elevated slow-wave
      frequency and spike events and transiently suppressed the myoelectric response to
      ricin. In contrast, intraluminal capsaicin alone did not alter myoelectric
      activity but produced a sustained inhibition of the response to ricin. Eicosanoid
      production was unchanged by capsaicin alone. Intraluminal capsaicin blocked
      increases in leukotriene C4 and prostaglandin E2 during inflammation, an effect
      that paralleled its inhibition of myoelectric activity. Thus the contribution of
      sensory afferents to altered motility during acute ileitis involves the release
      of mucosal inflammatory mediators that influence neural control of smooth muscle.

PMID- 9277425
TI  - Nitric oxide as modulator of cholinergic neurotransmission in gastric muscle of
      rabbits.
AB  - The effects of the nitric oxide (NO) synthesis inhibitors, NG-nitro-L-arginine (L
      NNA) and NG-nitro-L-arginine methyl ester (L-NAME), on the electrical field
      stimulation (EFS)-induced inhibitory responses were investigated. EFS caused, in
      strips contracted by means of substance P (SP), prostaglandin F2 alpha (PGF2
      alpha), or carbachol (CCh), a fast relaxant response that, depending on
      stimulation frequency and strip tension, could be followed by a slower, sustained
      relaxation. The NO synthesis inhibitors blocked the EFS-induced fast relaxations
      and often reversed them into contractions; these effects were greatly
      counteracted in SP- or PGF2 alpha-treated strips by scopolamine or atropine. In
      CCh-precontracted strips, either L-NNA or L-NAME became progressively unable to
      block the EFS-induced fast relaxations as the CCh concentration was increased.
      The NO synthesis inhibitors greatly reduced the sustained relaxant responses
      elicited either by EFS or exogenous vasoactive intestinal polypeptide (VIP). The
      results indicate that the NO synthesis inhibitors abolish the neurally induced
      fast relaxation by interfering with the cholinergic excitatory pathway. The
      involvement of both VIP and NO in sustained relaxations is also suggested.

PMID- 9277427
TI  - Correlation of electrical and contractile activities of the cricopharyngeus
      muscle in the cat.
AB  - We correlated the electrical and contractile activities of the cricopharyngeus
      (CP) to better understand the function of the CP and the upper esophageal
      sphincter (UES). In 40 decerebrate cats, we recorded resting and active tension
      of the CP and CP force and electromyographic (EMG) activity simultaneously during
      electrical stimulation of the pharyngoesophageal (PE) nerve, esophageal
      distension, or swallowing. In six intact cats, the change in diameter of the UES
      during food swallows was determined in two planes using videofluoroscopy. We
      found that resting tension of the CP developed quickly with stretch, and the
      strain-energy function, y = 6.5e3.4(z-1), fit (r = 0.94 +/- 0.06) this
      relationship. Active tension peaked at 1.68 +/- 0.03 times resting length, which
      is greater than the maximum distension during swallowing. Activation and
      relaxation of the CP occurred in approximately 50 and 120 ms, respectively. PE
      nerve stimulation bilaterally caused a force equal to approximately 90% of the
      summed force generated by separate stimulation of each PE nerve. The magnitude of
      the EMG response of the contralateral CP was approximately 18% of the ipsilateral
      response to unilateral PE nerve stimulation. We conclude that the CP exhibits
      tension throughout its physiological range of stretch. The CP functions more like
      a bilateral than a single contiguous muscle, and more like cardiac than striated
      muscle with regard to its passive elastic properties.

PMID- 9277426
TI  - Gastrogastric reflexes regulating gastric tone and their relationship to
      perception.
AB  - Our aim was to investigate in humans the gastrogastric reflexes that regulate
      gastric tone and their relationship to perception. In nine healthy subjects,
      liquid distension (in 100-ml steps), warm stimuli (in 3 degrees C increments),
      and cold stimuli (in 6 degrees C decrements) were randomly applied in the stomach
      for 3 min at 8-min intervals. Gastric tone was measured as isobaric volume
      changes of air by a barostat, and perception was scored by a graded (0-6)
      questionnaire. Liquid accommodation produced an additional expansion of isobaric
      air maintained by the barostat (51 +/- 13 ml with 100 ml of liquid filling, P <
      0.05), but this effect became inconsistent with further filling. An accommodation
      like reflex was best evidenced by warm stimulation below the discomfort threshold
      (58 +/- 13 ml relaxation at 47 +/- 1 degrees C, P < 0.05). By contrast, cooling
      below discomfort induced a reflex contraction (-62 +/- 22 ml change at 18 +/- 2
      degrees C, P < 0.05). In conclusion, gastric tone, i.e., accommodation and
      contraction, is modulated by a net of reflexes that arise from the proper wall of
      the stomach below the discomfort threshold.

PMID- 9277428
TI  - Tapeworm infection decreases intestinal transit and enteric aerobic bacterial
      populations.
AB  - Intestinal myoelectric patterns in rats are altered after chronic luminal
      infection with the tapeworm Hymenolepis diminuta. This study evaluates whether
      these altered patterns were associated with changes in intestinal fluid transit
      and endogenous enteric microbe levels. Luminal transit, measured throughout the
      small intestine during the interdigestive state, was significantly decreased
      during tapeworm infection. Reduced transit was regional, occurring in the same
      location as that of the tapeworm and maximal myoelectric alterations. In other
      experimental systems, aerobic and anaerobic bacterial overgrowth is associated
      with decreased transit; however, reduced transit during tapeworm infection was
      unexpectedly associated with decreased numbers of aerobic bacteria, whereas
      anaerobic bacterial populations remained unchanged. The lack of overgrowing
      endogenous microflora suggests that overgrowth is not responsible for tapeworm
      stimulated alterations in host myoelectric patterns. We speculate that a tapeworm
      secretion could be responsible for both transit and motility changes while
      delayed intestinal transit could prevent tapeworm expulsion, aid the tapeworms'
      migration, and contribute to the digestion and absorption of nutrients by hosts
      and/or parasites.

PMID- 9277429
TI  - Cholinergic nerves mediate stress-induced intestinal transport abnormalities in
      Wistar-Kyoto rats.
AB  - We have previously reported that acute stress alters intestinal transport
      physiology in Wistar-Kyoto rats, a stress-susceptible strain. In this study, we
      tested the hypothesis that the abnormalities in these rats are due to cholinergic
      mechanisms. Atropine- or saline-treated rats were exposed to acute restraint
      stress, and, subsequently, electrophysiological parameters of excised jejunal
      segments were assessed in Ussing chambers. Compared with the parent Wistar rat
      strain, Wistar-Kyoto rats demonstrated significantly greater stress-induced
      changes in ion secretion and permeability. The activity of cholinesterase in
      intestinal mucosal homogenates was significantly less in Wistar-Kyoto than in
      Wistar rats. Atropine pretreatment of rats before stress corrected the epithelial
      pathophysiology. Our results suggest that stress stimulated the release of
      acetylcholine, resulting in altered epithelial function in these genetically
      predisposed rats.

PMID- 9277430
TI  - Inhibition of mechanical activity by neurotensin in rat proximal colon:
      involvement of nitric oxide.
AB  - The aim of the present study was to define the nature of inhibitory action of
      neurotensin in rat proximal colon. Mechanical activity was detected as changes of
      intraluminal pressure. Neurotensin (10(-10) to 10(-7) M), in the presence of
      atropine (10(-6) M), guanethidine (10(-6) M), and nifedipine (10(-8) M), induced
      a tetrodotoxin-insensitive inhibitory effect characterized by the complete
      disappearance of the spontaneous phasic contractions. The inhibitory effect of
      neurotensin (10(-7) M) was abolished by scorpion venom (Leiurus quinquestriatus
      hebraeus) (10(-6) g/ml) or high K+ (40 mM KCl), whereas it persisted in the
      presence of omega-conotoxin GVIA, (10(-7) M). N omega-nitro-L-arginine methyl
      ester (L-NAME) (10(-4) M to 3 x 10(-4) M) antagonized the inhibitory response to
      neurotensin but did not affect the response to norepinephrine. L-Arginine (5 x
      10(-3) M) prevented the effect of L-NAME. The contractile action of neurotensin,
      observed in the absence of atropine and nifedipine, was potentiated by L-NAME
      (10(-4) M); L-arginine (5 x 10(-3) M) prevented the L-NAME effect. The present
      results suggest that in rat proximal colon the inhibitory action of neurotensin
      is largely due to production of nitric oxide (NO), likely released from neural
      prejunctional sites. Ca2+ influx through N-type channels is not a required step
      in the mechanism of neurotensin inhibitory action.

PMID- 9277431
TI  - Nuclear Fos immunoreactivity in guinea pig myenteric neurons following activation
      of motor activity.
AB  - To identify enteric neurons activated during intestinal motor activity, we
      examined myenteric plexus of guinea pig small intestinal segments for expression
      of the immediate early gene product, Fos. Fos immunoreactivity was detected
      immunohistochemically following in vitro manipulations, which included
      distension, electrical stimulation, exposure to forskolin, and peristalsis. All
      of these manipulations induced neuronal Fos expression, which was prevented by
      tetrodotoxin, indicating that expression depended on nerve activity. Distension
      induced Fos expression was blocked by omega-conotoxin and significantly reduced
      by hexamethonium, indicating that neurons expressing Fos immunoreactivity were
      activated synaptically. Blocking smooth muscle contraction with nicardipine
      reduced expression of neuronal Fos, suggesting that muscle tone influences
      neuronal activity. Calbindin-immunoreactive putative sensory neurons did not
      express Fos during distension, peristalsis, or exposure to forskolin and
      expressed Fos only weakly after strong electrical stimulation. Conversely,
      calretinin-immunoreactive ascending excitatory interneurons and longitudinal
      muscle motoneurons exhibited Fos immunoreactivity after all experimental
      manipulations. These results indicate that Fos expression can, with some caution,
      be used to identify classes of enteric neurons activated by different stimuli
      under various experimental conditions.

PMID- 9277432
TI  - Identification of a bile acid response element in the cholesterol 7 alpha
      hydroxylase gene CYP7A.
AB  - The transcriptional activity of the cholesterol 7 alpha-hydroxylase gene CYP7A is
      repressed by bile acids. Taurine conjugates of chenodeoxycholate and
      deoxycholate, but not cholate and ursodeoxycholate, inhibited the CYP7A
      promoter/luciferase reporter activity in transient transfection assays in Hep G2
      cells. A region from nucleotide (nt) -74 to -55 was found to mediate bile acid
      response. However, deletion of this bile acid response element (BARE-I) enhanced
      reporter activity but did not eliminate the bile acid response. This is due to
      the presence of another BARE-II located in a conserved region between nt -149 and
      -128. Deletion or mutations of these sequences reduced promoter activity and
      abolished bile acid repression. This BARE-II shares an identical AGTTCAAG core
      sequence with BARE-I. Electrophoretic mobility shift assays of BARE-I and BARE-II
      probes using Hep G2 nuclear extract and the partially purified binding activity
      of nt -65/-54 DNA-affinity column revealed that the same or a similar nuclear
      protein might bind to both BAREs. BARE-II is the major BARE involved in the
      transcriptional repression of the CYP7A gene by hydrophobic bile acids.

PMID- 9277433
TI  - Bile acids stimulate proliferative and secretory events in large but not small
      cholangiocytes.
AB  - Accumulation of bile acids (BA) and cholangiocyte proliferation occur in
      cholestasis, but BA effects on the proliferative and secretory capacity of
      cholangiocytes are undefined. Cholangiocyte proliferation coupled with increased
      expression of H3 histone and secretin receptor (SR) genes and secretin-stimulated
      adenosine 3',5'-cyclic monophosphate (cAMP) levels is limited to large
      cholangiocytes. We isolated pooled small and large cholangiocytes and studied the
      effect of taurocholic (TC) and taurolithocholic (TLC) acids on proliferation, by
      measurement of H3 histone gene expression, and secretion, by measurement of SR
      gene expression, cAMP levels, and Cl-/HCO3- exchanger activity. In pooled
      cholangiocytes, TC and TLC increased H3 histone (12-fold) and SR (3-fold) gene
      expression and both spontaneous (1.4-fold) and secretin-induced (4-fold) cAMP
      response. TC and TLC increased H3 histone (10-fold) and SR (2-fold) gene
      expression and secretin-induced cAMP response and Cl-/HCO3- exchanger activity (3
      fold) only in large cholangiocytes. In large cholangiocytes, BA may have a
      signaling function in the modulation of ductal secretion.

PMID- 9277434
TI  - Inhibition of nitric oxide synthesis improves detoxication in inflammatory liver
      dysfunction in vivo.
AB  - Inflammatory stimulation of the liver induces nitric oxide (NO) biosynthesis and
      suppression of detoxication. In this study the effect of NO biosynthesis on
      cytochrome P-450 (CYP) enzyme activity was investigated by comparing in vivo and
      in vitro assays. To establish liver inflammation, CD rats were injected with
      Corynebacterium parvum (C. parvum) suspension. After 5 days NO biosynthesis was
      highly induced as indicated by increased NO2- plus NO3- serum concentrations. At
      the same time the aminopyrine breath test (ABT), measuring CYP activity in vivo,
      was reduced to 42% and the in vitro assay of aminopyrine turnover was suppressed
      to 12% of NaCl- injected controls. When C. parvum-injected animals were treated
      with the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA), CYP activities
      significantly improved with an ABT of 76% and an in vitro aminopyrine turnover of
      47% of controls. Neither C. parvum injections nor L-NMMA treatment resulted in a
      significant change of CYP protein concentrations. These data indicate that
      suppression of xenobiotic metabolism can be attenuated by inhibition of NO
      biosynthesis during an ongoing process of inflammation.

PMID- 9277435
TI  - Potassium currents in atrial and ventricular myocytes from a rat model of
      cirrhosis.
AB  - The underlying mechanisms for the electrophysiological abnormalities that develop
      as a consequence of cirrhosis of the liver have been studied by recording three
      different K+ currents in mammalian heart tissue. Single myocytes from the atria
      and ventricles of sham-operated and bile ductligated (BDL) cirrhotic adult rats
      were current and voltage clamped using standard whole cell methods. In
      ventricular myocytes from cirrhotic animals, measurements of the current-voltage
      relationships, voltage dependence of inactivation, and reactivation kinetics of
      K+ currents showed that the only significant functional changes (within the
      physiological range of membrane potentials) were decreases in the density of
      expression of 1) I(t), a Ca(2+)-independent transient outward K+ current, and 2)
      Isus, a delayed rectifier K+ current. The decreases in I(t) and Isus contribute
      to the prolonged Q-T interval of the electrocardiogram that has been described in
      cirrhotic patients. Measurement of K+ currents in atrial myocytes demonstrated
      that there were no significant differences in any of the K+ current densities
      between sham and BDL animals, although reactivation kinetics of I(t) were slowed
      somewhat.

PMID- 9277436
TI  - Gene transfer into hepatoma cell lines via the serpin enzyme complex receptor.
AB  - The serpin enzyme complex receptor (SECR) expressed on hepatocytes binds to a
      conserved sequence in alpha 1-antitrypain (alpha 1-AT) and other serpins. A
      molecular conjugate consisting of a synthetic peptide (C1315) based on the SECR
      binding motif of human alpha 1-AT covalently coupled to poly-L-lysine was used to
      introduce reporter genes into hepatoma cell lines in culture. This conjugate
      condensed DNA into spheroidal particles 18-25 nm in diameter. When transfected
      with the SECR-directed complex containing pGL3, Hep G2 cells that express the
      receptor, but not Hep G2 cells that do not, expressed a peak luciferase activity
      of 538,731 +/- 144,346 integrated light units/mg protein 4 days after
      transfection. Free peptide inhibited uptake and expression in a dose-dependent
      manner. Complexes of DNA condensed with polylysine or LC-sulfo-N-succinimidyl-3
      (2-pyridyldithio)propionate-substituted polylysine were ineffective. Transfection
      with a plasmid encoding human factor IX produced expression in Hep G2 (high) and
      HuH7 cells that express SECR but not Hep G2 (low) cells that lack the receptor.
      Fluorescein-labeled C1315 peptide labeled 9-31% of Hep G2 (high), 10-14% of HuH7,
      and 0.6-3.4% of Hep G2 (low) cells, and when the lac Z gene was transfected, only
      these cells expressed beta-galactosidase. SECR-mediated gene transfer gives
      efficient, specific uptake and high-level expression of three reporter genes, and
      the system merits further study for gene therapy.

PMID- 9277438
TI  - Prevention of parenteral nutrition-induced gut hypoplasia by coinfusion of
      glucagon-like peptide-2.
AB  - Maintaining rats on total parenteral nutrition (TPN) for 6 days significantly
      reduced mass (-34%), protein (-32%), and DNA (-35%) in small intestine and colon
      (29-37% decrease). Coinfusion of glucagon-like peptide-2 (GLP-2) normalized each
      of these variables in duodenum, jejunum, and ileum, but not in colon.
      Histological analysis of tissue revealed normal mucosa thickness and villus
      height in small intestine of GLP-2-treated rats, whereas nontreated rats
      maintained on TPN exhibited villus shortening (-30%) and thinning (-23%) of
      mucosa. These results suggest that hormonal alterations may be more important
      than an absence of luminal nutrition in TPN-associated mucosal changes.
      Additionally, GLP-2 normalization of gut mucosa permits accurate assessment of
      the influence of reversal of hypoplasia on gut barrier function.

PMID- 9277437
TI  - Survival of human pancreatic enzymes during small bowel transit: effect of
      nutrients, bile acids, and enzymes.
AB  - The activity of pancreatic enzymes declines during aboral intestinal transit. We
      tested the hypothesis that survival of pancreatic enzyme activities during
      intestinal transit is affected by amounts or concentrations of calories,
      nutrients, bile acids, or pancreatic enzymes entering the segments of the small
      intestine. An oroileal tube was placed in 26 healthy humans. The tube had
      duodenal, jejunal, and ileal infusion ports for nonabsorbable markers and
      aspiration ports in the distal duodenum, distal jejunum, and distal ileum. Four
      infusates of different proportions of protein, fat, and carbohydrate were infused
      continuously into the duodenum at 40, 90, and 160 kcal/h. Of the nutrients
      infused into the proximal duodenum, 21 +/- 3, 51 +/- 7, and 39 +/- 5% of fat,
      protein, and carbohydrate, respectively, were delivered to the distal duodenum.
      During duodenoileal transit, lipase, chymotrypsin, amylase, and trypsin lost 71
      +/- 5, 63 +/- 5, 43 +/- 7, and 38 +/- 9% of activity, respectively (P < 0.01 vs.
      distal duodenum). During duodenojejunal transit, the activity of each enzyme
      decreased more than 35% (P < 0.01 vs. distal duodenum), and infusion of more
      calories into the duodenum improved survival of all enzymes except trypsin (P <
      0.05). During jejunoileal transit, greater amounts and concentrations of calories
      and carbohydrate improved survival of only lipolytic activity (P < 0.01, P <
      0.05, respectively), and loss of lipolytic activity correlated directly with
      delivery of bile acids (r = 0.56, P = 0.05) and chymotrypsin (r = 0.80, P =
      0.001) to the distal jejunum. We conclude that intraluminal nutrients increase
      survival of enzyme activities in the proximal intestine. After absorption of
      nutrients, the action of chymotrypsin and bile acids decrease lipolytic activity
      more than activity of other enzymes.

PMID- 9277439
TI  - Reduced vasodilator response to ANF in hypoxia-induced pulmonary hypertension in
      the newborn piglet.
AB  - Recent evidence suggests that, in adult animals with hypoxia-induced pulmonary
      hypertension, atrial natriuretic factor (ANF) may modulate pulmonary vascular
      tone and may have a protective effect. However, its role in the pathogenesis of
      pulmonary hypertension of the newborn is unknown. We hypothesized that, in the
      newborn, hypoxia-induced pulmonary hypertension would result in ANF receptor
      downregulation, resulting in decreased dilator response, favoring pulmonary
      vasoconstriction and vascular remodeling. Therefore, we studied, in 1-day-old
      piglets exposed to hypoxia (fraction of inspired O2 0.10) for 3 or 14 days to
      induce pulmonary hypertension, 1) ANF release by measuring circulating levels of
      ANF by radioimmunoassay in pulmonary artery and veins, 2) pulmonary vascular
      reactivity to ANF using isolated perfused lungs, and 3) binding characteristics
      by examining the concentration dependence of ANF binding and competitive binding
      of 125I-labeled ANF with ANF, brain natriuretic peptide, C-type natriuretic
      peptide, and the specific ligand for ANF clearance receptor on microsomes from
      pulmonary arteries (down to 100 microns). ANF circulating levels are increased
      after exposure to hypoxia compared with normoxia, reaching significance at 14
      days (P < 0.005). The magnitude of ANF dilator response is diminished after
      exposure to hypoxia (P < 0.05). Saturation studies reveal that the number of ANF
      receptors is diminished in hypoxia after 3 days but reaches significance after 14
      days (P < 0.01) compared with their respective normoxic control. At either
      condition, the majority of these receptors are of the functional type, whereas
      clearance receptors are virtually undectable. These results suggest that hypoxia
      increases circulating ANF and causes a decreased responsiveness of the pulmonary
      vasculature to ANF. Receptor down-regulation may explain part of the reduced
      dilator response, although the involvement of other mechanisms is not excluded.

PMID- 9277440
TI  - Protection of perfused lung from oxidant injury by inhibitors of anion exchange.
AB  - Hyperoxic lung injury is enhanced in isolated perfused lungs (IPL) in the
      presence of L-arginine. Reactive O2 species such as superoxide anion (O2-.)
      produced during hyperoxia are known to react with nitric oxide to form the strong
      oxidant species peroxynitrite. The appearance of O2-. in red blood cell membranes
      in vitro and in buffer-perfused lung preparations can be inhibited by the
      stilbene compound 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) DIDS
      also inhibits anion exchange across the cell membrane regulated by a family of
      anion exchange proteins (AE). In this study, we hypothesized that anion exchange
      inhibitors would prevent lung injury from hyperoxia and L-arginine (O2 + L-Arg)
      by decreasing O2-. flux into the vascular space of the IPL. We found that both
      DIDS and a structurally distinct anion transport blocker, dipyridamole, protected
      the rabbit IPL from pulmonary hypertension and edema produced by O2 + L-Arg. The
      protective effect was associated with increased nitrite concentrations in the
      perfusate. Protection also was conferred when sodium bicarbonate in the perfusion
      buffer was replaced with either sodium thiosulfate or N-2-hydroxyethylpiperazine
      N'-2-ethanesulfonic acid (HEPES). In lungs perfused with thiosulfate or HEPES
      containing buffer, protection from O2 and L-arginine was also associated with
      diminished detection of reducing activity consistent with O2-. in the vascular
      space. Western blot analysis of lung protein and immunocytochemical staining of
      lung sections using antibodies against rabbit red blood cell AE1 and mouse
      gastric AE2 peptide showed that lung contains membrane protein antigenically
      similar to gastric AE2. These data suggest the possibility that inhibition of AE
      or other anion transporters may play an important role in mediating oxidative
      lung injury.

PMID- 9277441
TI  - Upregulation of alveolar liquid clearance after fluid resuscitation for
      hemorrhagic shock in rats.
AB  - The primary objective of this study was to test the hypothesis that a
      catecholamine-dependent mechanism would upregulate alveolar liquid clearance
      after fluid resuscitation from 15 min of hemorrhagic shock. Anesthetized rats
      were hemorrhaged to a mean arterial pressure of 35 mmHg for 15 min and were
      resuscitated with a 4% albumin solution. Alveolar liquid clearance was measured 5
      h later by the concentration of protein in the distal airspaces over 1 h after
      instillation of a 5% albumin solution into one lung. Hemorrhaged rats developed a
      severe metabolic acidosis that was associated with a significant rise-in plasma
      epinephrine levels throughout the study. There was a 60% increase in alveolar
      liquid clearance in hemorrhaged and resuscitated rats compared with control rats.
      Amiloride (10(-4) or 10(-6) M), propranolol (10(-4) M), or bilateral
      adrenalectomy inhibited the increase in alveolar liquid clearance. This effect
      was reproduced by the intravenous administration of epinephrine in
      adrenalectomized and hemorrhaged rats. Thus these data provide evidence for a
      catecholamine-dependent regulation of sodium transport that protects the
      airspaces against flooding several hours after fluid resuscitation from
      hemorrhagic shock.

PMID- 9277442
TI  - ANG II stimulates endothelial nitric oxide synthase expression in bovine
      pulmonary artery endothelium.
AB  - Although angiotensin II (ANG II) is a known pulmonary vasoconstrictor, the
      purpose of this study was to examine the effect of ANG II on pulmonary artery
      endothelial cell nitric oxide synthase (ecNOS) mRNA and protein expression.
      Cultured bovine pulmonary artery endothelial (BPAE; passages 5-8) cells were
      incubated for 0-12 h with 10(-6) M ANG II. Total RNA was extracted, and ecNOS
      expression was assessed by Northern blot analysis. In BPAE cells, ecNOS mRNA was
      significantly increased 2.4 +/- 0.3-fold (P < 0.05 vs. basal; n = 5) 6 h after
      the addition of ANG II over basal levels. In & similar time course, it was found
      that ecNOS protein concentrations are increased 247 +/- 62% (P < 0.05 vs. basal;
      n = 8) over basal levels 4 h after ANG II addition. There is a second protein
      peak 8 h after ANG II addition in which ecNOS was increased 333 +/- 145% over
      basal (P < 0.05, n = 3). These data suggest that ANG II stimulates ecNOS mRNA
      expression and are followed by increased levels of ecNOS protein in cultured BPAE
      cells, consistent with an observed increase in nitrite production. Both the
      increase in ecNOS protein and mRNA expression could be inhibited with the ANG II
      receptor antagonist saralasin. Additionally, actinomycin D, an inhibitor of
      transcription, prevented the rise in mRNA at 6 h while cycloheximide inhibited
      the initial protein peak. The effects of ANG II on ecNOS were specific for the
      pulmonary artery endothelium. Addition of ANG II did not increase ecNOS protein
      or mRNA expression in parallel studies in bovine coronary artery endothelium. The
      stimulation of ecNOS by ANG II may act to protect the lung and maintain low
      pulmonary artery pressures in the renin-angiotensin model of systemic
      hypertension.

PMID- 9277444
TI  - Antisense inhibition of 85-kDa cPLA2 blocks arachidonic acid release from airway
      epithelial cells.
AB  - Inflammatory cytokines play a critical role in the initiation and perpetuation of
      inflammation. Several cytokines are known to increase the production of
      arachidonic acid (AA) metabolites, which may mediate cytokine-induced acute and
      chronic inflammation. Although cytokines upregulate phospholipase A2 (PLA2) in
      several target cells, the contribution of individual PLA2 to cytokine-induced AA
      release and eicosanoid production remains unclear because of the existence of
      various forms of cellular PLA2. To examine the role of 85-kDa cytosolic PLA2
      (cPLA2) in cytokine-induced AA release, a system was developed to inhibit the
      expression of cPLA2 in a human bronchial epithelial cell line (BEAS-2B cells) by
      antisense RNA. Cells stably expressing antisense cPLA2 exhibited decreased cPLA2
      protein levels as well as decreased cPLA2 activity assayed in vitro. The effects
      of cytokines interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF
      alpha), and interleukin-1 alpha (IL-1 alpha) on the release of prelabeled [3H]AA
      were then tested in cells stably transfected with vector alone as well as cells
      transfected with cPLA2 antisense plasmid. IFN-gamma (300 U/ml), TNF-alpha (20
      ng/ml), and IL-1 alpha (20 ng/ml) all induced a significantly increased release
      of prelabeled [3H]AA after 15 min to 2 h of treatment in control cells, and their
      effects were significantly reduced in cells transfected with cPLA2 antisense
      vector. These results demonstrate a critical role of cPLA2 in inflammatory
      cytokine-induced AA metabolism.

PMID- 9277443
TI  - Regulation of [Ca2+]i in canine airway smooth muscle by Ca(2+)-ATPase and
      Na+/Ca2+ exchange mechanisms.
AB  - We investigated Ca2+ handling in airway smooth muscle (SM) using fura 2
      fluorescence, ion currents, and contractions as indexes of intracellular Ca2+
      concentration ([Ca2+]i). Carbachol evoked a transient elevation of [Ca2+]i, the
      magnitude of which was smaller and the rate of decay faster at 37 degrees C,
      indicating that some temperature-sensitive mechanism contributed to recovery.
      Removal of external Na+ had no effect on agonist-evoked Ca2+ transients or
      contractions or on spontaneous Ca(2+)-dependent K+ currents. Cyclopiazonic acid,
      a selective inhibitor of the sarcoplasmic reticulum (SR) Ca(2+)-ATPase, evoked a
      transient elevation of [Ca2+]i and contraction, markedly slowed recovery of the
      cholinergic Ca2+ transient, and depleted the SR. Sodium vanadate evoked a
      sustained elevation of [Ca2+]i and markedly slowed the decay of the cholinergic
      Ca2+ transient. We conclude that, in canine airway SM, 1) Na+/Ca2+ exchange makes
      at best only a minor contribution to Ca2+ homeostasis, 2) the SR Ca(2+)-ATPase
      compensates for spontaneous and agonist-triggered release of Ca2+, and 3) [Ca2+]i
      homeostasis involves some other extrusion pathway, likely the plasmalemmal Ca(2+)
      ATPase.

PMID- 9277445
TI  - Alveolar type II cell cNOS activity and ATP levels are increased by lung
      surfactant or DPPC vesicles.
AB  - In a previous study, we reported that nitric oxide (.NO) affects surfactant
      synthesis and ATP levels in alveolar type II cells and suggested that there is
      constitutive nitric oxide synthase (cNOS) activity in the cells. In the present
      study, we performed experiments to confirm further the presence of cNOS and to
      determine the effects of lung surfactant on type II cell .NO and ATP levels. The
      supernatant from freshly isolated cells contains .NO (0.26 +/- 0.08 nmol/10(6)
      cells). During incubation, the cells produce additional .NO at a rate of
      approximately 0.3 nmol.10(5) cells-1.h-1. .NO formation is inhibited by 28-46% by
      three inhibitors of cNOS and inducible NOS (iNOS), NG-monomethyl-L-arginine (L
      NMMA), L-N5-(1-iminoethyl)ornithine hydrochloride, and NG-nitro-L-arginine methyl
      ester, but a specific inhibitor of iNOS, aminoguanidine, has no effect. The
      production of .NO is reduced in Ca(2+)-free medium, is stimulated by the Ca2+
      ionophore A-23187, and is independent of extracellular L-arginine. One known type
      of cNOS, endothelial NOS (eNOS), can be detected in the cells by using Western
      blot analysis. Incubation of the cells with lung surfactant leads to a relatively
      rapid (approximately 15 min), concentration-dependent increase in .NO formation
      that reaches levels as high as 238 +/- 14% of control. The surfactant effects
      appear to be caused by its major component, dipalmitoyl phosphatidylcholine
      (DPPC). Exposure of type II cells to DPPC results in maximal increases in .NO
      formation, ATP content, and O2 consumption, which are 268 +/- 32, 234 +/- 24, and
      131 +/- 6% of control, respectively. The DPPC-induced increases in .NO, ATP, and
      O2 consumption are inhibited by L-NMMA. These results confirm the presence of
      type II cell cNOS and suggest that it may have a role in the cellular processing
      of lung surfactant.

PMID- 9277447
TI  - Expression of transforming growth factor-beta receptors during hyperoxia-induced
      lung injury and repair.
AB  - Lung injury and repair processes involve many cellular activities, including cell
      growth, differentiation, and remodeling of extracellular matrix components.
      Transforming growth factor-beta (TGF-beta) is a major class of signaling peptide
      growth factors regulating these cellular activities. Type I (T beta RI) and type
      II (T beta RII) receptors for TGF-beta are transmembrane serine/threonine kinases
      that are essential for TGF-beta signaling. To gain insight into the possible
      molecular mechanisms of lung injury and repair, we investigated the expression of
      T beta RI and T beta RII in an acute hyperoxia-induced model of lung injury and
      repair. Localization of message expression of T beta RI and T beta RII in oxygen
      exposed rat lung tissue was analyzed by using in situ hybridization. T beta RI
      mRNA expression was found in the interstitium, capillaries, and the alveolar
      septa of rat lungs exposed for 60 h to 100% oxygen. The distribution of T beta
      RII mRNA in oxygen-exposed rat lung tissue overlapped the localization of T beta
      RI mRNA. Temporal changes of T beta RI and T beta RII mRNA expressions in rat
      lung during hyperoxic exposure and repair were examined by Northern analysis. We
      found that expression of T beta RI was upregulated in adult rats undergoing
      prolonged exposure to 100% oxygen, and the increase of T beta RI expression
      persisted during 2 wk of repair of lung injury. The pattern of T beta RII
      expression during hyperoxic exposure and repair was distinct from that of T beta
      RI. The expression of T beta RII increased with a peak at 3 days postexposure and
      then declined after 7 days of repair. Changes of T beta RI and T beta RII protein
      expressions in rat lung during hyperoxic exposure and repair were examined
      further by Western blot analysis, which correlated with the mRNA expression. The
      results suggest that T beta RI and T beta RII may play important roles during the
      lung injury and repair by mediating signaling activity of TGF-beta and may
      regulate interactions between the mesenchyme and the epithelium.

PMID- 9277446
TI  - Maintenance of the differentiated type II cell phenotype by culture with an
      apical air surface.
AB  - The study of differentiated functions of alveolar type II cells has been hampered
      because of the lack of good in vitro systems. We report that culture of type II
      cells on collagen gels with an apical surface exposed to air promotes expression
      of differentiated type II cell characteristics. Cells cultured in this manner are
      cuboidal, contain lamellar bodies, and produce tubular myelin; in addition, they
      secrete phosphatidylcholine in response to exogenous ATP. Cultures contain mRNA
      for surfactant proteins A, B, and C and surfactant proteins A, B, and D. In
      contrast, when type II cells are cultured with an apical surface exposed to
      liquid rather than to air, the cells are squamous, do not express surfactant
      proteins or their respective mRNA, and do not contain lamellar bodies or produce
      tubular myelin. Type II cells cultured on plastic for 7 days, which no longer
      express mRNA for surfactant proteins, can be induced to express these mRNA by
      changing culture conditions to that of an air surface. The culture system
      described in this paper should be useful for studies of surfactant metabolism,
      regulation of alveolar epithelial phenotypic expression, and the processing of
      transiently expressed transgenes.

PMID- 9277448
TI  - Intracellular calcium responses in CF/T43 cells: calcium pools and influx
      pathways.
AB  - We studied the intracellular free Ca2+ concentration ([Ca2+]i) response to
      histamine in a cystic fibrosis airway epithelial cell line (CF/T43). Histamine
      (100 microM; duration approximately 10 min) biphasically increased [Ca2+]i, with
      a rapid initial peak (30-45 s) followed by a smaller second peak that lasted for
      several minutes before returning to baseline. Neither peak specifically depended
      on Ca2+ influx. Exposure to bradykinin (10 microM) elicited a single peak that
      lasted 3-3.5 min before returning to baseline. Bradykinin increased intracellular
      inositol 1,4,5-trisphosphate (IP3), which peaked and returned to baseline within
      150 s. Histamine also increased IP3 monophasically, but the peak was brief (< 20
      s). Both phases of the Ca2+ response to histamine exhibited similar
      responsiveness to histamine concentration and sensitivity to antagonists.
      Cimetidine or thioperamide (1 mM) had no effect on the second peak. Pyrilamine
      blocked the second peak at concentrations similar to those required to block the
      initial peak. Activation of the second peak was observed at a threshold
      concentration of 1 microM comparable with the threshold of the initial peak.
      Neither adenosine 3',5'-cyclic monophosphate, guanosine 3',5'-cyclic
      monophosphate, nor cyclic ADP (cADP)-ribose altered the second phase of the
      histamine response.

PMID- 9277449
TI  - TGF-beta isoforms differentially attenuate EGF mitogenicity and receptor activity
      in fetal lung mesenchymal cells.
AB  - To evaluate signaling interactions, combinations of epidermal growth factor (EGF)
      and transforming growth factor-beta (TGF-beta) isoforms were applied to primary
      fetal mouse lung mesenchymal cells isolated at 16 days of gestation. The three
      isoforms of TGF-beta had similar mitogenic potentials, as assessed by thymidine
      incorporation (half-maximal effective concentration approximately 2 ng/ml).
      However, combined exposure to EGF and TGF-beta yielded an isoform-dependent
      attenuation of EGF-induced mitogenesis. Combinations of 20 ng/ml EGF and 2 ng TGF
      beta 1, TGF-beta 2, or TGF-beta 3 resulted in thymidine incorporation values
      0.76, 0.74, and 0.86 times that of EGF alone, respectively; attenuation of EGF
      mitogenicity, interactions between EGF and TGF-beta isoforms, and differences
      between isoforms were all statistically significant by analysis of variance.
      Treatment with TGF-beta isoforms significantly reduced EGF-induced receptor
      angiotensin II substrate phosphorylation. TGF-beta isoform-specific signaling
      also significantly attenuated EGF-induced phosphorylation of the mitogen
      activated protein (MAP) kinase extracellular signal-regulated kinase 2. These
      results suggest that isoform-specific TGF-beta signaling modulates the EGF signal
      transduction pathway upstream of MAP kinase.

PMID- 9277450
TI  - Surfactant protein A activates NF-kappa B in the THP-1 monocytic cell line.
AB  - The expression of many genes for which products are involved in inflammation is
      controlled by the transcriptional regulator nuclear factor (NF)-kappa B. Because
      surfactant protein (SP) A is involved in local host defense in the lung and
      alters immune cell function by modulating the expression of proinflammatory
      cytokines as well as surface proteins involved in inflammation, we hypothesized
      that SP-A exerts its action, at least in part, via activation of NF-kappa B. We
      used gel shift assays to determine whether SP-A activated NF-kappa B in the THP-1
      cell line, a human monocytic cell line. Activation of NF-kappa B in THP-1 cells
      by SP-A doses as low as 1 microgram/ml occurred within 30 min of SP-A treatment,
      peaked at 60 min, and then declined. This activation is inhibited by known
      inhibitors of NF-kappa B or by simultaneous treatment of the cells with
      surfactant lipids. Moreover, the NF-kappa B inhibitors blocked SP-A-dependent
      increases in tumor necrosis factor-alpha mRNA levels. These observations suggest
      a mechanism by which SP-A plays a role in the pathogenesis of some lung
      conditions and point to potential therapeutic measures that could be used to
      prevent SP-A induced inflammation in the lung.

PMID- 9277451
TI  - Expression of glycogen phosphorylase isozymes in developing rat lung.
AB  - Glycogen accumulates to significant levels in epithelial cells of the developing
      respiratory tract. Mobilization of glycogen stores is regulated differentially
      along the respiratory epithelium such that glycogenolysis in the alveolar
      epithelium (the site of surfactant synthesis) precedes that in the bronchial and
      bronchiolar epithelium. The initial step in glycogen degradation is catalyzed by
      glycogen phosphorylase, which exists as three genetically distinct isozymes
      referred to as muscle, liver, and brain isoforms. The goal of this study was to
      characterize the temporal and spatial expression of each of the glycogen
      phosphorylase isozymes in developing lung to determine which isoform(s) was
      associated with glycogen mobilization in the fetal type II epithelial cell. RNA
      levels encoding glycogen phosphorylase were assessed by ribonuclease protection
      assay using isoform-specific antisense probes. RNAs encoding the brain and liver
      isozymes were detected in isolated day 20 fetal type II epithelial cells and at
      lower levels in adult type II cells. The muscle isoform RNA was barely detectable
      in fetal type II cells and was undetectable in adult type II cells. Expression of
      brain and liver isoform RNAs was higher in whole fetal lung than in fetal type II
      cells. Consistent with this result, in situ hybridization studies demonstrated
      widespread expression of the brain and liver isoforms in developing lung tissues;
      in contrast, expression of the muscle isoform was restricted to the pulmonary
      vein. Glycogen phosphorylase enzyme activity corresponding to the brain isoform
      was clearly detected in isolated fetal type II cells; however, the majority of
      enzyme activity migrated as two bands with distinct electrophoretic mobilities
      that may have been the result of isoform heterodimerization. Collectively, these
      results suggest that the brain and liver isoforms of glycogen phosphorylase may
      be involved in mobilization of type II cell glycogen during late fetal lung
      development.

PMID- 9277452
TI  - Early increase in expression of surfactant protein A gene in type II cells from
      silica-treated rats.
AB  - Silica is known to cause an increase in lung surfactant and to promote type II
      cell hypertrophy and hyperplasia. Two populations of type II cells can be
      isolated from silica-treated rats: type IIA cells that are similar to normal type
      II cells and type IIB cells that are larger, contain more surfactant
      phospholipids, and have increased rates of phospholipid biosynthesis. As much
      less is known about the influence of silica on the amounts of surfactant proteins
      (SPs) in type II cells, we examined expression of the genes for all four SPs in
      types IIA and IIB cells isolated from rats 1, 3, and 7 days after a single
      intratracheal injection of silica. There was a rapid increase in expression of
      the SP-A gene in type II cells from the silica-treated animals. SP-A mRNA content
      was 8- to 10-fold greater in types IIA and IIB cells isolated 1 day after silica
      injection than in type II cells from saline-injected animals. SP-A mRNA levels
      were also elevated in the cells isolated on days 3 and 7 after silica injection,
      but the extent of the increase was less than in the cells isolated on day 1 and
      declined with time after injection. SP-B, SP-C, and SP-D mRNA levels were 2.5- to
      4-fold greater in type IIA cells on day 3 after silica injection than in control
      type II cells. However, those mRNA levels were not significantly increased in the
      type IIA cells isolated on days 1 and 7 or in type IIB cells at any time point.
      These data show that silica causes a rapid and substantial increase in expression
      of the SP-A gene in type II cells.

PMID- 9277454
TI  - Endogenous retinoids increase perinatal elastin gene expression in rat lung
      fibroblasts and fetal explants.
AB  - During late gestation, the lungs of rats contain retinyl esters, but their
      concentration decreases considerably at the time of birth. The regulation of the
      acquisition and utilization of these stored retinoids remains poorly understood,
      although it has been hypothesized that they are involved in surfactant production
      and alveolar septal formation. Previous investigations demonstrated that
      exogenous retinoic acid increases elastin production in cultured neonatal lung
      fibroblasts and increases the number of alveoli when it is administered to
      neonatal rats. It has been hypothesized that these pulmonary stores of retinyl
      esters may regulate the perinatal expression of various genes in the lung,
      including elastin. To test this hypothesis, inhibitors of retinoid metabolism
      were used to reduce the flux of retinyl esters to retinoic acid, and the effects
      of this maneuver on elastin gene expression were analyzed. Inhibitors of alcohol
      and aldehyde dehydrogenases and of retinyl ester hydrolases decreased the steady
      state level of tropoelastin mRNA without reducing alpha 1(I) procollagen mRNA.
      The magnitude of the effects of the inhibitors was retinol dependent and was
      significantly reduced in lung tissue that was obtained from vitamin A-deficient
      fetuses. These findings suggest that the late gestational pulmonary stores of
      retinoids may increase elastin gene expression during the fetal and early
      postnatal life in the rat.

PMID- 9277453
TI  - HSP27 elevated in mild allergic inflammation protects airway epithelium from
      H2SO4 effects.
AB  - Inflammation in allergic individuals is hypothesized to elevate stress proteins
      [heat shock proteins (HSP)] in airway epithelium, which may protect cells from
      further adverse conditions. Allergic, either asthmatic or not, and normal
      volunteers participated in a 2-day segmental allergen challenge bronchoscopic
      procedure. Bronchial epithelium was obtained before and after challenge.
      Epithelium was exposed to medium with H2SO4 (pH5), returned to medium at pH 7.4,
      and finally harvested for Western blotting with anti-27-kDa HSP (HSP27) antibody.
      Prechallenge epithelium of all subjects had significantly inhibited ciliary
      function by H2SO4 (pH 5) conditions (P < 0.001); only epithelium of normals
      recovered (P = 0.02). Allergic subjects with mild inflammation (< 50
      micrograms/ml increase in albumin in bronchoalveolar lavage) had significantly
      increased HSP27 postchallenge (P = 0.01) and little ciliary dysfunction at pH 5,
      whereas subjects with severe inflammation (> 50 micrograms/ml increase in
      albumin) had little change in HSP27 and significant ciliary inhibition (P =
      0.02). Normal epithelium had similar trends in HSP27 and equivalent inhibition of
      ciliary activity at pH 5 before and after allergen challenge. These data indicate
      that mild inflammation to allergen elevates HSP27 stress protein levels, thereby
      potentially protecting epithelial function from additional adverse conditions.

PMID- 9277455
TI  - Regulation of transferrin gene expression during lung development and injury.
AB  - Transferrin (TF), the major iron-transporting protein in vertebrates, is mainly
      synthesized in the liver. Although its source in lung is unknown, TF is a major
      inhibitor for lipid peroxidation and microbial propagation in lung fluid, and
      iron-free TF has been shown in rabbits to decrease the severity of respiratory
      failure and to improve surfactant activity. This study shows that TF is produced
      and secreted by the lung. In baboons and humans. TF gene expression displays
      distinct temporal patterns in different lung cells as revealed by in situ
      hybridization. Although expression of TF mRNA in submucosal glands remains active
      during development and throughout adulthood, its level in airway epithelial
      increases with advancing gestational age, reaches its peak before birth, declines
      6-12 mo after birth, and diminishes in the older adult. In premature baboons
      maintained on ventilatory support, expression of TF mRNA is suppressed in both
      airway epithelium and glands. TF production by airway epithelia before birth most
      likely prevents oxidative damage in the newborn period, and its loss during
      injury may allow further lung damage.

PMID- 9277456
TI  - Ionic regulation of proton chemical (pH) and electrical gradients in lung
      lamellar bodies.
AB  - This study investigated the pH (chemical) and electrical gradients in lamellar
      bodies, the acidic surfactant-secreting organelles of lung epithelial type II
      cells, by following the uptake of a weak fluorescent base, quinacrine, and a
      membrane potential-sensitive dye, bis-(3-phenyl-5-oxoisoxazol-4-yl)pentamethine
      oxonol (oxonol V). In isolated lung lamellar bodies, the ATP-dependent uptake of
      both agents could be inhibited by bafilomycin A1, a reportedly specific inhibitor
      of vacuolar-type H(+)-ATPase (V-ATPase) and could be dissipated by a
      protonophore, carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone, suggesting
      that the V-ATPase generates an electropositive interior. A closely linked uptake
      of Cl- neutralizes the positive electrical potential and increases the proton
      pump activity. The uptake of quinacrine, but not oxonol V, was decreased by Na+.
      This effect of Na+ could be prevented by dimethylamiloride, suggesting the
      presence of electroneutral Na+/H+ exchanger in lamellar body membranes. The
      initial rates of quinacrine and oxonol V uptake were increased by bumetanide, but
      only in the presence of Na+, K+, and Cl-, suggesting that the lamellar bodies
      also contain an outwardly directed electroneutral Na(+)-K(+)-2Cl- cotransporter.
      Thus three ion transporters, H(+)-translocating V-ATPase, Na+/H+ exchanger, and
      Na(+)-K(+)-2Cl- cotransporter, appear to determine the chemical and electrical
      gradients across the lamellar body membrane.

PMID- 9277457
TI  - NO elicits prolonged relaxation of bovine pulmonary arteries via endogenous
      peroxynitrite generation.
AB  - We previously reported that acute exposure of endothelium-removed bovine
      pulmonary arteries (BPA) to high levels (0.1 mM) of peroxynitrite (ONOO-) caused
      a prolonged guanosine 3',5'-cyclic monophosphate-related relaxation that appeared
      to be mediated through a thiol-dependent generation of nitric oxide (NO). In this
      study, we examined the importance of endogenous ONOO- formation in the regulation
      of BPA force generation by elevated physiological levels of NO. Exposure of BPA
      precontracted with 30 mM KCl to approximately 50 nM NO for 2 min caused a
      subsequent prolonged relaxation of KCl-induced force and an increased release of
      NO (measured in head space gas after a 5-min deoxygenation with 95% N2-5% CO2).
      This subsequent release of NO was reduced after depletion of tissue glutathione
      with diethyl maleate (DEM). Also, the NO-elicited prolonged relaxation of BPA was
      reversed by post-NO treatment with 10 microM methylene blue (MB; which inhibits
      guanylate cyclase stimulation by NO) or 1 microM oxyhemoglobin (which traps NO).
      Furthermore, inhibiting the biosynthesis of endogenous superoxide anion (O2-.)
      with 1 microM diphenyliodonium (DPI) or scavenging O2-. with 10 mM Tiron also
      promoted reversal of the NO-elicited prolonged relaxation seen in BPA after NO
      gas exposure. During exposure of BPA smooth muscle to approximately 50 nM NO gas,
      there appears to be a marked increase in ONOO- formation as detected by a DPI-
      and Tiron-inhibitable prominent increase in luminol-dependent chemiluminescence
      and a decrease in O2-. levels as detected by a reduction in lucigenin-dependent
      chemiluminescence during exposure to NO. Thus, during exposure to elevated
      physiological levels of NO, BPA appear to produce ONOO-, a species that seems to
      participate in prolonging the initial relaxation to NO through a thiol-dependent
      trapping and/or regeneration of NO.

PMID- 9277458
TI  - Effects of reactive metabolites of oxygen and nitrogen on gelatinase A activity.
AB  - The regulation of matrix metalloproteinase activity is crucial for maintaining
      the proper balance of tissue remodeling vs. injury. Metalloproteinase proenzymes
      are activated when the active site zinc is exposed via a cysteine switch
      mechanism. Peroxynitrite, the product generated from the interaction between
      nitric oxide and superoxide, has been shown to release zinc from zinc-thiolate
      groups, suggesting that it might alter metalloproteinase activity. This study
      examined the effects of nitric oxide and superoxide generators on gelatinase A
      activity. Results showed that nitric oxide alone had no effect on gelatinase A
      activity relative to control, whereas superoxide-derived metabolites increased
      activity. The simultaneous generation of both nitric oxide and superoxide caused
      an inhibition of gelatinase A activity. This inhibition was reversed by the
      addition of hemoglobin, superoxide dismutase, or sodium urate, suggesting that
      peroxynitrite and/or peroxynitrous acid caused the inhibition. Authentic
      peroxynitrite also inhibited gelatinase A activity. We postulate that the
      relative fluxes of nitric oxide and superoxide at sites of inflammation may
      modulate metalloproteinase activity and thus affect matrix protein metabolism.

PMID- 9277459
TI  - Upregulation of acidic fibroblast growth factor during development of
      experimental lung fibrosis.
AB  - Fibroblast proliferation and extracellular matrix accumulation are crucial in the
      pathogenesis of lung fibrosis. Fibroblast growth factor (FGF)-1 participates in
      both processes, but its role in lung fibrogenesis has not been evaluated. We
      analyzed the expression of FGF-1 and of FGF receptor (FGFR) in a model of lung
      fibrosis induced in rats with paraquat plus hyperoxia. Experimental and control
      animals were killed at 48 h and 2, 4, and 8 wk, and the lungs were studied by in
      situ hybridization, immunohistochemistry, and Northern blot. In normal lungs,
      scattered macrophages contained FGF-1. In contrast, at all times examined, the
      injured lungs exhibited FGF-1 transcript and the immunoreactive protein, mainly
      in alveolar epithelial cells and macrophages. In advanced fibrotic lesions,
      fibroblasts also appeared stained. Northern blot corroborated the upregulation of
      FGF-1 mRNA. FGFR was not observed in normal lungs, whereas it was strongly
      increased in the damaged lungs and was virtually immunolocalized in the same cell
      types as the corresponding ligand. These findings suggest that FGF-1 and FGFR are
      actively synthesized during the development of pulmonary fibrosis.

PMID- 9277460
TI  - Activation of ERK and JNK1 MAP kinases in cultured lung tissue.
AB  - The biochemical mechanisms responsible for lung cell growth and proliferation are
      not well defined during tissue injury. We previously showed stimulation of DNA
      synthesis in intact lung tissue cultured in vitro after exposure to elevated
      fractions of O2. By use of this in vitro model, the current study examined the
      enzymatic activities of the extracellular-regulated kinase (ERK) and c-Jun NH2
      terminal kinase (JNK) mitogen-activated protein (MAP) kinase pathways. ERK and
      JNK activities were transiently elevated in lung tissue cultured under serum-free
      conditions. Raf-1 kinase, the primary upstream activator of the ERK pathway, was
      also transiently activated, suggesting a receptor-mediated ERK activation.
      Phosphorylation of the guanine nucleotide exchange protein p170 son of sevenless
      further suggested a receptor-mediated activation of the ERK pathway. c-Fos and c
      Jun expression, downstream targets of ERK and JNK, was dramatically increased in
      cultured tissue compared with uncultured tissue. After the initial transient
      activation, ERK and JNK could be reactivated with specific agonists,
      demonstrating that these signaling pathways were functional. These findings
      demonstrate activation of the ERK and JNK MAP kinase pathways in intact lung
      tissue and provide a model system to define signaling pathways involved in lung
      tissue remodeling injury.

PMID- 9277461
TI  - Preferential uptake of small-aggregate fraction of pulmonary surfactant in vitro.
AB  - Homeostasis of pulmonary surfactant requires metabolic clearance of surfactant
      forms with decreased surface activity. Rabbit pulmonary surfactant was labeled in
      vivo with rhodamine-labeled dipalmitoylphosphatidylethanolamine (R-DPPE),
      isolated, and fractionated into large- and small-aggregate subfractions by
      differential centrifugation. Endocytosis of large (LA)- and small (SA)-aggregate
      surfactant by a mouse lung epithelial cell line (MLE-12) was evaluated in vitro
      by epifluorescence microscopy. More SA than LA surfactant was taken up by MLE-12
      cells. Endocytosis of SA and LA surfactant was inhibited by preincubation of the
      subfractions with surfactant protein A and 3.3 mM Ca2+. The difference in uptake
      between SA and LA surfactant was lost for reconstituted organic extracts of the
      subfractions. Much of the difference in uptake of SA and LA surfactant may be
      attributed to the greater concentration of surfactant protein A in LA surfactant.

PMID- 9277462
TI  - Muscarinic receptors inhibit ATP-sensitive K+ channels in swine tracheal smooth
      muscle.
AB  - The patch-clamp technique was used to characterize a cromakalim-induced current
      and its regulation by muscarinic receptors in tracheal smooth muscle cells.
      Cromakalim (10 microM) activated a steady-state increase of 33-292 pA (91.2 +/-
      8.8 pA, n = 43) in whole cell current, consistent with the activation of ATP
      sensitive K+ (KATP) channels. Acetylcholine (10 nM-1 microM), added cumulatively,
      inhibited the cromakalim-induced current by 23.6 +/- 14.9 to 73.9 +/- 4.6%. This
      inhibition was blocked by pretreatment with atropine (1 microM). The cromakalim
      induced current was also inhibited 83.0 +/- 8.3% by phorbol 12-myristate 13
      acetate (100 nM, n = 6). The inhibition of the cromakalim-induced current by
      acetylcholine (1 microM) and phorbol 12-myristate 13-acetate (100 nM) was reduced
      to 27.3 +/- 3.1% (n = 10) and 32.8 +/- 7.8% (n = 3), respectively, in the
      presence of staurosporine (100 microM). We conclude that muscarinic receptor
      stimulation inhibits KATP channel activity through the activation of protein
      kinase C. These findings suggest that KATP channels may play a role in the
      regulation of membrane potential and contractility in airway smooth muscle.

PMID- 9277464
TI  - Structure and function of cardiac sodium and potassium channels.
AB  - The application of patch-clamp and molecular approaches has resulted in an
      increasingly refined understanding of the molecular entities underlying cardiac
      sodium and potassium currents. The sodium current results from expression of a
      single large alpha-subunit, whereas multiple potassium currents and potassium
      channel alpha-subunits have been identified. Recapitulation of some ion currents
      in heterologous expression systems requires not only expression of alpha-subunits
      but also ancillary (beta) subunits. Domains common to functions such as
      activation, inactivation, and drug block are now being identified in alpha- and
      beta-gene products. Variability in the expression or function of individual ion
      channel genes is an increasingly recognized source of variability in the ion
      currents recorded in heart cells under physiological conditions (e.g. during
      development) as well as in disease.

PMID- 9277463
TI  - Extracellular ATP and adenosine cause apoptosis of pulmonary artery endothelial
      cells.
AB  - ATP acts as an intracellular energy source and an extracellular signaling
      molecule. We report that extracellular ATP causes apoptosis in pulmonary artery
      endothelial cells, as assessed by morphological changes and internucleosomal DNA
      degradation. We investigated the mechanism of this effect using release of
      tritiated soluble DNA as a marker for apoptosis. We conclude that the metabolite
      adenosine is responsible for the apoptotic effect of ATP, since nucleotides that
      can be degraded to adenosine, as well as adenosine itself, cause DNA damage,
      whereas nonmetabolizable ATP analogs and uridine 5'-triphosphate are inactive.
      Furthermore, the ecto-5'-nucleotidase inhibitor alpha, beta-methylene-ADP blocks
      ATP-induced DNA fragmentation. The adenosine receptor agonist 5'-N
      ethylcarboxamide adenosine does not cause DNA fragmentation, and adenosine
      receptor antagonists do not block adenosine-induced apoptosis. However, the
      nucleoside transport inhibitor dipyridamole prevents extracellular ATP-induced
      DNA cleavage. These findings indicate that ATP- and adenosine-mediated apoptosis
      are mediated via intracellular events rather than through cell surface
      receptor(s). The adenosine metabolites inosine, hypoxanthine, and xanthine do not
      cause apoptosis. The adenosine analogs 3-deazaadenosine and MDL-28842, which are
      not metabolized and are S-adenosylhomocysteine hydrolase inhibitors, also cause
      DNA fragmentation. Therefore, we speculate that extracellular ATP and adenosine
      cause apoptosis of pulmonary artery endothelial cells by altering methylation
      reactions that require S-adenosylmethionine as the methyl donor. We speculate
      that ATP released from cells undergoing cytolysis or degranulation may cause
      endothelial cell death. Endothelial cell apoptosis may be important in acute
      vascular injury or in limiting angiogenesis.

PMID- 9277465
TI  - Attenuation of heat shock protein expression by coronary occlusion in
      hypertrophied hearts.
AB  - Hearts hypertrophied by pressure-overload are more susceptible to ischemia than
      nonhypertrophied hearts, which may result from the attenuation of self-protective
      responses. Because heat shock proteins (HSPs) are reported to protect against
      ischemic injuries, we hypothesized that HSP expression by coronary occlusion may
      be attenuated in hypertrophied hearts. We banded the ascending aorta to develop
      ventricular hypertrophy and put a snare around the left coronary artery in rats.
      After 4 wk, coronary occlusion was applied by tightening the snare for 5 or 10
      min in rats with and without aortic banding. The hearts were excised 0, 0.5, 1,
      2, 4, 8, 12, and 24 h after coronary occlusion. Ischemic and nonischemic
      myocardial tissues were obtained after the snare was tightly tied, and dye was
      infused from the aorta. The mRNAs and protein of 72-kDa HSP (HSP 72) and/or 73
      kDa HSP (HSP 73) were detected by Northern and Western blot analyses. Protein and
      mRNA levels of HSPs expressed by 5-min coronary occlusion in hypertrophied hearts
      (left ventricular weight, 577 +/- 16 mg) were lower compared with those in
      control hearts (462 +/- 9 mg). A longer period of coronary occlusion (10 min)
      elevated the attenuated expression to a level similar to that in control hearts.
      Treatment with an angiotensin-converting enzyme (ACE) inhibitor (cilazapril, 10
      15 mg.kg(-1).day(-1)) for 4 wk preserved HSP mRNA expression even in hearts with
      ascending aortic banding. In hypertrophied hearts, HSP 72 and 73 expression by
      coronary occlusion was attenuated and was modulated by the duration of coronary
      occlusion and by ACE inhibitor treatment.

PMID- 9277466
TI  - Vagal stimulation decreases left ventricular contractility mainly through
      negative chronotropic effect.
AB  - Although an increase in vagal tone is known to slow heart rate (HR), whether it
      also depresses left ventricular contractility through mechanisms independent of
      the bradycardic effect remains unknown. The chief aim of this investigation,
      therefore, was the separation of the observed vagally mediated depression of
      ventricular contractility into direct and indirect vagal effects, the latter
      resulting via negative chronotropism. In 12 anesthetized, sympathectomized open
      chest rabbits, we measured left ventricular contractility through determination
      of the end-systolic elastance (Ees). We found that tonic vagal stimulation
      administered at 0, 5, and 10 Hz decreased both HR (226.9 +/- 39.7, 201.9 +/-
      25.7, and 171.3 +/- 18.5 beats/min, respectively; P = 0.0003) and Ees (109.5 +/-
      25.7, 85.1 +/- 34.1, and 71.9 +/- 33.1 mmHg/ml, respectively; P = 5 x 10(-6)) in
      a frequency-dependent fashion. However, we observed that as long as HR was kept
      constant through fixed-rate atrial pacing, vagal stimulation resulted in little
      or no change in Ees. Thus we conclude that the negative inotropic effect of vagal
      stimulation is attributable primarily to its negative chronotropic effect when
      sympathetic tone is minimal.

PMID- 9277467
TI  - Cardiovascular responses to glutamate stimulation of diagonal band of Broca.
AB  - Experiments were done in alpha-chloralose-anesthetized, paralyzed, and
      artificially ventilated rats to investigate the effect of L-glutamate stimulation
      of the diagonal band of Broca (DBB) on arterial pressure (AP) and heart rate
      (HR). Stimulation of the horizontal limb of the DBB (hDB) elicited decreases in
      both mean AP (MAP; -32.3 +/- 2.5 mmHg; n = 37) and HR (-32.5 +/- 3.8 beats/min; n
      = 33) at 84% of the sites stimulated. Stimulation of the vertical limb of the DBB
      (vDB) elicited significantly smaller decreases in MAP (-9.7 +/- 1.0 mmHg; n = 19)
      and HR (-13.5 +/- 1.8 beats/min; n = 7) at approximately 13% of the sites
      stimulated. Intravenous administration of the muscarinic receptor blocker
      atropine methylbromide had no effect on the magnitude of the MAP and HR responses
      to stimulation of the hDB. In contrast, administration of the nicotinic receptor
      blocker hexamethonium bromide abolished both the depressor and the bradycardic
      responses elicited by stimulation of the hDB. These data indicate that the hDB
      contains neurons that exert cardiovascular depressor effects and that these
      circulatory effects are mediated by the inhibition of sympathetic vasoconstrictor
      fibers to the vasculature, and cardioacceleratory fibers to the heart.

PMID- 9277468
TI  - Mechanical forces regulate focal adhesion and costamere assembly in cardiac
      myocytes.
AB  - To determine whether the formation and maintenance of focal adhesions and
      costameres in cardiac myocytes are influenced by the mechanical forces that they
      transmit, we mechanically unloaded these cells by inhibiting their spontaneous
      contractile activity with the calcium-channel blocker nifedipine (12 microM).
      Interference-reflection and fluorescence microscopy revealed that within 24 h of
      arrest, beta 1-integrin- and vinculin-positive focal adhesions and costameres
      were disrupted. Loss of mature beta 1-integrin from the cell surface was observed
      in cell surface-labeling experiments and in Western blots. Subjecting nonbeating
      cells to a 5% static stretch for 24 h resulted in an increase of 21% for beta 1
      integrin and 39% for vinculin. Stretching beating cells resulted in 71 and 9%
      increases, respectively. Intracellular concentrations of pre-beta 1 were not
      affected by contractile activity or by stretch. Our results indicate that
      mechanical forces stabilize the cellular levels of beta 1-integrin and vinculin
      by possibly regulating their association with the formation and maintenance of
      focal adhesions and costameres.

PMID- 9277469
TI  - Role of adenosine in norepinephrine-induced coronary vasodilation.
AB  - Adenosine has been postulated to be the physiological transmitter coupling
      increases in coronary blood flow to increases in myocardial metabolism. The
      purpose of this experiment was to evaluate the role of adenosine in the coronary
      hyperemia due to norepinephrine. In 11 anesthetized, closed-chest canine
      preparations, the left main coronary artery was cannulated and perfused with
      blood at 100 mmHg. Coronary blood flow and myocardial oxygen consumption were
      measured, and interstitial adenosine concentration was estimated from arterial
      and coronary venous measurements using a distributed model. Adenosine receptor
      blockade with 8-phenyltheophylline (8-PT) was used to shift the adenosine dose
      response curve 12-fold. During intracoronary norepinephrine infusion, coronary
      blood flow and myocardial oxygen consumption increased similarly before and after
      8-PT, demonstrating a lack of an effect from the adenosine receptor blockade.
      Before 8-PT, estimated interstitial adenosine increased to a vasoactive
      concentration (220 nM); however, the temporal correlation with coronary blood
      flow was poor. After 8-PT, a similar increase in estimated interstitial adenosine
      was found, demonstrating that there was no augmentation in adenosine
      concentration to overcome the adenosine receptor blockade. Thus adenosine could
      not be responsible for the increase in coronary blood flow after adenosine
      receptor blockade and therefore is not required for norepinephrine-induced
      hyperemia.

PMID- 9277470
TI  - Inorganic phosphate and coronary perfusion pressure mediate contractile
      dysfunction during mild ischemia.
AB  - During mild graded ischemia in perfused rat hearts, we (V.M. Figueredo, R.
      Brandes, M. W. Weiner, B. M. Massie, and S. A. Camacho. J. Clin. Invest 90: 1794
      1802, 1992) previously found a relationship between decreased left ventricular
      developed pressure (LVDP) and increased Pi, in which intracellular pH, cytosolic
      Ca2+ concentration ([Ca2+]i), ATP, and free-energy change of ATP hydrolysis were
      not altered enough to affect contractility. However, the contribution of
      decreased coronary perfusion pressure (CPP) to decreased LVDP could not be
      determined. Thus, in the present study, graded hypoxia in perfused rat hearts (95
      37.5% O2) was used to increase Pi to similar levels produced during mild ischemia
      without altering CPP and minimizing changes of other potential mediators of
      contractile dysfunction. 31P-magnetic resonance spectroscopy and indo 1
      fluorescence were used to assess energy metabolites and [Ca2+]i, respectively.
      The relationship between LVDP and Pi during graded hypoxia was fit to a
      monoexponential (LVDP = 105 x e-0.04Pi). These data were compared with the
      relationship of LVDP and Pi during mild ischemia (LVDP = 106 x e-0.08Pi) (V. M.
      Figueredo, R. Brandes, M. W. Weiner, B. M. Massie, and S. A. Camacho. J. Clin.
      Invest 90: 1794-1802, 1992). The exponential constant, which describes the effect
      of Pi on LVDP, was 50% lower during graded hypoxia relative to mild ischemia.
      This suggests that another mediator, which accounted for approximately 50% of the
      decrease of LVDP during mild ischemia, was not present during hypoxia. Because
      CPP decreased during ischemia but not hypoxia, these data suggest that CPP and Pi
      contribute similarly in mediating contractile dysfunction during mild ischemia.

PMID- 9277471
TI  - Transient Ca2+ overload alters Ca2+ handling in rat cardiomyocytes: effects on
      shortening and relaxation.
AB  - Transient Ca2+ overload in cardiomyocytes occurs during pathophysiological
      conditions. The aim of the present study was to investigate the effects of
      transient Ca2+ overload on shortening and relaxation in isolated rat
      cardiomyocytes electrically stimulated at 0.5 Hz and to examine whether transient
      Ca2+ overload induces alterations in Ca2+ handling and myofilament sensitivity.
      Fractional shortening and shortening velocity fell to 79 +/- 5% (P < 0.05) and 78
      +/- 4% (P < 0.01) 2 min after exposure to high Ca2+. A transient decrease in
      resting length, a reduction in relaxation velocity to 86 +/- 7% (P < 0.05), and a
      prolonged time of relaxation with 8.3 +/- 4.3% (P < 0.05) were also observed.
      Systolic fluorescence ratio using fura 2 as the Ca2+ indicator fell by 11.0%, and
      the decline of the fluorescence ratio was prolonged by 29.8%. By applying
      caffeine, we observed a significant reduction in sarcoplasmic reticulum Ca2+
      content after transient Ca2+ overload. A significant reduction in myofilament
      sensitivity was also observed. In conclusion, the systolic dysfunction observed
      after transient Ca2+ overload is the result of both decreased systolic Ca2+ and
      reduced myofilament sensitivity. The relaxation abnormalities are most likely
      caused by altered Ca2+ handling, since we observed a reduction in the
      sarcoplasmic reticulum Ca2+ content and a prolongation of the decline of the fura
      2 transient.

PMID- 9277472
TI  - Severe diastolic dysfunction with preserved energy conversion efficiency after
      countershock.
AB  - The left ventricular (LV) mechanical performance and the LV myocardial oxygen
      consumption (VO2)-to-pressure-volume area (PVA; LV total mechanical energy index)
      relationship were measured in isovolumic contraction of isolated blood-perfused
      dog hearts before and after direct current (DC) countershocks. At a constant LV
      volume, DC shocks increased LV end-diastolic pressure progressively and
      strikingly with the progression of myocardial edema and a marked prolongation of
      the time constant of LV pressure decay. In contrast, DC shocks changed neither
      the slope of the LV end-systolic pressure-volume relationship nor the contractile
      efficiency (the slope of the Vo2-PVA relationship). The oxygen cost of
      contractility (the slope of the relationship between PVA-independent VO2 and LV
      contractility) increased 27% after DC shocks. However, the magnitude of this
      change was considerably smaller than that previously reported in postischemic
      stunned myocardium (123%), suggesting that the adverse effect of DC shocks on the
      energy cost of excitation-contraction coupling is relatively minor. Thus, despite
      the severe diastolic dysfunction, DC shocks do not substantially impair either
      the efficiency of cross-bridge cycling or calcium cycling. Myocardial
      interstitial edema is more likely a potential mechanism of diastolic dysfunction
      after DC shocks.

PMID- 9277474
TI  - Characterization of energy metabolism and blood flow distribution in myocardial
      ischemia in hemorrhagic shock.
AB  - To characterize the mechanisms for myocardial ischemia induced by hemorrhagic
      shock, 29 dogs were subjected to hemorrhage at a mean aortic pressure (MAoP) of
      30-60 mmHg. After 10 min of hemorrhage, the beating hearts were rapidly cross
      sectioned and freeze clamped to visualize the two-dimensional distribution of
      myocardial ischemia with NADH fluorescence (NADH-F) in 22 dogs. NADH-F was
      developed at an MAoP of 40 mmHg or less and involved both the subendocardial half
      and the subepicardial half of the left ventricle [34 +/- 14 vs. 20 +/- 14% (P <
      0.05) and 65 +/- 16 vs. 52 +/- 15% (not significant) of the cross-sectional area
      of the left ventricular slice at MAoP levels of 40 and 30 mmHg, respectively].
      Magnified NADH-F photography demonstrated heterogeneously distributed
      microischemic lesions with a columnar shape (mode of short-axis length, 60-80
      microns). NADH-F-guided microsamplings revealed higher NADH and lactate
      concentrations in a positive NADH-F area than those in a negative NADH-F area.
      The ratio of endocardial to epicardial blood flow was maintained at a relatively
      high level (1.07 +/- 0.07 and 0.88 +/- 0.07 at MAoP levels of 40 and 30 mmHg,
      respectively; n = 7 dogs), and the reactive hyperemia was preserved as well. In
      conclusion, myocardial ischemia in early hemorrhagic shock was characterized by
      minimal transmural heterogeneity and marked heterogeneity between contiguous
      small regions.

PMID- 9277473
TI  - Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by
      hyperthyroidism.
AB  - This study was conducted to examine whether the renin-angiotensin system
      contributes to hyperthyroidism-induced cardiac hypertrophy without involving the
      sympathetic nervous system. Sprague-Dawley rats were divided into control
      innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid
      denervated groups using intraperitoneal injections of thyroxine and 6
      hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in
      hyperthyroid groups (63%), and this increase was only partially inhibited by
      sympathetic denervation. Radioimmunoassays and reverse transcription-polymerase
      chain reaction revealed increased cardiac levels of renin (33%) and angiotensin
      II (53%) and enhanced cardiac expression of renin mRNA (225%) in the hyperthyroid
      groups. These increases were unaffected by sympathetic denervation or 24-h
      bilateral nephrectomy. In addition, losartan and nicardipine decreased systolic
      blood pressure to the same extent, but only losartan caused regression of
      thyroxine-induced cardiac hypertrophy. These results suggest that thyroid hormone
      activates the cardiac renin-angiotensin system without involving the sympathetic
      nervous system or the circulating renin-angiotensin system; the activated renin
      angiotensin system contributes to cardiac hypertrophy in hyperthyroidism.

PMID- 9277475
TI  - Vinculin phosphorylation and barrier failure of coronary endothelial monolayers
      under energy depletion.
AB  - We studied the hypothesis that, in energy-depleted endothelial cells, Ca(2+)
      dependent activation of protein kinase C (PKC) causes phosphorylation of vinculin
      and that this effect is involved in the early loss of endothelial barrier
      function. Vinculin localization and phosphorylation, PKC activity, and albumin
      permeability were studied in cultured coronary endothelial monolayers from rats.
      Ten minutes after the onset of metabolic inhibition by 5 mM potassium cyanide and
      5 mM 2-deoxy-D-glucose, immunofluorescence of vinculin at cell-to-cell and cell
      to-matrix contacts faded, whereas total cellular vinculin content remained
      unchanged. During the same time period, vinculin phosphorylation at tyrosine and
      serine sites increased by 3.9- and 3.5-fold, respectively. Vinculin
      phosphorylation was related to activation of PKC and an unidentified tyrosine
      kinase and was elicited by a rise in cytosolic Ca2+ within energy-depleted
      endothelial cells. Conditions inhibiting vinculin phosphorylation also reduced
      monolayer permeability induced by energy depletion. These data indicate that
      vinculin phosphorylation is involved in the progression of hyperpermeability
      during energy depletion in coronary endothelial monolayers.

PMID- 9277476
TI  - Anesthetics alter relative contributions of NO and EDHF in rat cremaster muscle
      microcirculation.
AB  - The contributions of the vasodilators nitric oxide (NO) and endothelium-derived
      hyperpolarizing factor (EDHF) were investigated in the rat cremaster muscle
      microcirculation during halothane, isoflurane, or ketamine anesthesia. After
      inhibition of prostaglandin synthesis with indomethacin, changes in diameter of
      fourth-order arterioles to acetylcholine (ACh) or bradykinin (BK) were studied in
      the presence or absence of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO
      synthase, and/or 20 mM K+, an inhibitor of EDHF action. L-NMMA inhibited ACh- and
      BK-induced vasodilation during isoflurane but not halothane or ketamine
      anesthesia. Superfusion of the muscle with buffer containing 20 mM K+ dilated
      arterioles. EDHF was responsible for most of the NO-independent response to ACh,
      because 20 mM K+ unmasked ACh-stimulated, NO-dependent relaxation during
      halothane or ketamine anesthesia. However, 20 mM K+ did not inhibit BK-induced
      vasodilation during halothane or ketamine anesthesia. Our data suggest that
      anesthetics can alter the balance between NO and EDHF vasodilation in the
      microcirculation and that NO-dependent mechanisms are enhanced and EDHF action
      inhibited during isoflurane anesthesia.

PMID- 9277477
TI  - Hypoxia-induced expression of VEGF is reversible in myocardial vascular smooth
      muscle cells.
AB  - We determined whether hypoxia-induced expression of vascular endothelial growth
      factor (VEGF) can be reversed by a normoxic environment. Dog myocardial vascular
      smooth muscle cells (MVSMCs) were exposed to hypoxia (1% O2) for 24 h and then
      returned to normoxia (20% O2). VEGF protein levels increased by more than
      fivefold after 24 h of hypoxia and returned to baseline within 24 h of the return
      of the cells to normoxia. Northern blot analysis showed that hypoxia caused a 5.5
      fold increase in VEGF mRNA, and, again, the expression was reversed after
      reinstitution of normoxia. Additional measurements showed that basic fibroblast
      growth factor and platelet-derived growth factor protein levels were not induced
      by hypoxia and that hypoxia caused a fourfold decrease in transforming growth
      factor-beta 1 protein levels. Hypoxia conditioned media from MVSMCs caused human
      umbilical vein endothelial cells to increase [3H]thymidine incorporation by
      twofold, an effect that was blocked in a dose-dependent manner by anti-human VEGF
      antibody. The hypoxia conditioned media had no effect on MVSMC proliferation.
      These findings suggest that VEGF expression can be bidirectionally controlled by
      tissue oxygenation, and thus support the hypothesis that VEGF is a physiological
      regulator of angiogenesis.

PMID- 9277478
TI  - alpha-Tocopheryl succinate inhibits monocytic cell adhesion to endothelial cells
      by suppressing NF-kappa B mobilization.
AB  - The adherence of monocytes to activated endothelium is an early event in
      atherogenesis. Because antioxidants have been considered to be of
      antiatherosclerotic potential, we investigated the effects of alpha-tocopherol
      (TCP) and its acetate and succinate esters on monocyte adhesion to cytokine
      stimulated human umbilical vein endothelial cells (HUVEC). Endothelial cells were
      treated with TCP, alpha-tocopherol acetate (TCP acetate), or alpha-tocopheryl
      succinate (TCP succinate) before stimulation with tumor necrosis factor-alpha
      (TNF-alpha; 10 U/ml, 6 h) or interleukin-1 beta (IL-1 beta; 10 U/ml, 6 h).
      Cytokine-stimulated cell surface expression of vascular cell adhesion molecule-1
      (VCAM-1, CD106) and E-selectin (ELAM-1, CD62E), but not of intercellular adhesion
      molecule-1 (ICAM-1, CD54), was time- and dose-dependently inhibited by TCP
      succinate but not by TCP or TCP acetate. TCP succinate (200 microM, 24 h) reduced
      TNF-induced VCAM-1 and E-selectin expression from a specific mean fluorescence
      intensity of 151 +/- 28 to 12 +/- 4 channels and from 225 +/- 38 to 79 +/- 21
      channels, respectively. Succinate alone had no effect. Decreased adhesion
      molecule expression was associated with a reduction of monocytic cell adhesion.
      TCP succinate (20 microM, 72 h), but not TCP (200 microM, 72 h), reduced U-937
      cell adhesion to TNF-alpha-stimulated (10 U/ml, 6 h) HUVEC by 30% (P < 0.025) and
      to IL-1 beta-stimulated HUVEC by 56% (P < 0.010). Electrophoretic mobility-shift
      assays of HUVEC nuclear proteins revealed a decrease in TNF-alpha-stimulated
      nuclear factor-kappa B (NF-kappa B) activation after pretreatment of HUVEC with
      TCP succinate but not with TCP, TCP acetate, or succinate alone. In conclusion,
      we demonstrate that the vitamin E derivative TCP succinate prevents monocytic
      cell adhesion to cytokine-stimulated endothelial cells by inhibiting the
      activation of NF-kappa B, further emphasizing the antiatherosclerotic potential
      of lipid soluble antioxidants.

PMID- 9277479
TI  - ACE inhibitors and cardiac ACE mRNA in volume overload-induced cardiac
      hypertrophy.
AB  - Quinapril, an angiotensin-converting enzyme (ACE) inhibitor with high affinity
      for cardiac ACE, prevents increases in both plasma and cardiac angiotensin II
      (ANG II) and development of cardiac hypertrophy after aortocaval shunt in rats.
      In contrast, enalapril, an ACE inhibitor with low affinity for cardiac ACE, only
      prevents the increase in plasma ANG II. In the present study, we assessed whether
      these differences between enalapril and quinapril reflect different inhibition of
      cardiac tissue ACE and local ANG II by measuring their effects on cardiac ACE
      mRNA. Treatment with enalapril (250 mg/l) and quinapril (200 mg/l in drinking
      water) was started 3 days before the shunt and sham surgery. After 1 wk of
      aortocaval shunt, the hearts were excised and the left ventricle and right
      ventricle were weighed and used for reverse transcriptase-polymerase chain
      reaction (RT-PCR) assays for ACE and phosphoglycerate kinase-1 (internal
      standard). Quinapril, but not enalapril, inhibited the development of cardiac
      hypertrophy by aortocaval shunt. The shunt increased ACE mRNA in both left and
      right ventricles about twofold. In animals with aortocaval shunt, quinapril
      markedly further upregulated ACE mRNA in both ventricles, whereas enalapril did
      not cause significant changes. In sham rats, both ACE inhibitors increased ACE
      mRNA, but the increase was more pronounced by treatment with quinapril. These
      studies show that in vivo ACE inhibitors with low (enalapril) vs. high
      (quinapril) affinity for cardiac ACE differ in their effects on cardiac ACE mRNA.
      This difference is more pronounced in volume overload-induced cardiac
      hypertrophy, presumably reflecting their different effects on cardiac ANG II.

PMID- 9277480
TI  - Effects of high-cholesterol and atherogenic diets on vascular relaxation in
      spontaneously hypertensive rats.
AB  - Hypercholesterolemia is associated with more rapid development of
      atherosclerosis, and hypertension is frequently associated with abnormal vascular
      function. Therefore, to investigate the role of hypercholesterolemia and
      hypertension on vascular function, we studied three groups of male rats (aged 6
      wk): normotensive Wistar-Kyoto rats (WKY) as a control group and spontaneously
      hypertensive rats (SHR) receiving either standard diet (SD; SHR-SD) or high
      cholesterol (1%) diet (ChD; SHR-ChD). Vascular reactivity was tested on isolated
      aortic rings at 4 wk and at 3 and 6 mo of diet. At 3 mo, endothelium-dependent
      relaxation to acetylcholine (ACh) and ADP was significantly reduced in SHR-ChD
      but not in SHR-SD compared with WKY. At 6 mo, relaxations to ACh were further
      impaired in both SHR groups compared with WKY. Endothelium-independent
      vasodilation to nitroglycerin (NTG) was not different in the three groups of
      animals throughout 6 mo of diet. In additional experiments, we evaluated vascular
      reactivity in rats fed with ChD enriched with an excess of vitamin D [atherogenic
      diet (AD)] capable of producing vascular atherosclerotic lesions. In particular,
      we studied three additional groups of WKY and SHR rats fed with SD, AD, or AD
      plus a nonhypotensive dose of the calcium antagonist nitrendipine (Nit).
      Vasodilation to ACh and ADP was significantly blunted in WKY-AD compared with WKY
      SD, whereas it was partially improved in WKY-Nit. There were no differences in
      endothelium-independent relaxation to NTG in the three WKY groups. In contrast,
      SHR-AD showed a marked reduction of endothelium-dependent and -independent
      vasodilation, but only endothelium-dependent vasodilation was preserved by
      addition of Nit to the diet. These data suggest that the development of vascular
      dysfunction in rat genetic hypertension is accelerated by ChD, in absence of
      detectable vascular lesions. Our study also shows that AD alters both vascular
      smooth muscle and endothelium-dependent relaxation. Low doses of Nit partially
      preserve endothelium-dependent vasodilation but do not affect the impairment of
      smooth muscle function in these rats.

PMID- 9277481
TI  - Protein kinase C-dependent regulation of the human AT1 promoter in vascular
      smooth muscle cells.
AB  - The expression level of angiotensin II (ANG II) type 1 receptors (AT1) determines
      the magnitude of ANG II signaling in vascular smooth muscle cells (VSMC). AT1
      mRNA expression in cultured bovine VSMC increased twofold after 8 h of protein
      kinase C (PKC) activation with phorbol 12-myristate 13-acetate (PMA), whereas
      stimulation with forskolin did not alter the AT1 mRNA level. The expression of
      AT1 promoter/exon 1 [-513/+92 base pairs (bp)] luciferase constructs transfected
      into VSMC increased 2.4-fold with PMA stimulation. In-gel kinase assays
      demonstrated rapid phosphorylation of mitogen-activating protein kinases (MAPK)
      ERK1 and ERK2 by PMA. Electrophoretic gel mobility shift assays showed sequence
      specific binding of nuclear proteins from PMA-activated VSMC, identified as
      activator protein 1 (AP-1) complex in competition assays, to a radiolabeled AT1
      promoter fragment (-368/-399 bp). Recombinant AP-1 binds in a sequence-specific
      manner to the -386/-399-bp region. Site-specific mutagenesis destroying the AP-1
      site, the adjacent polyoma enhancer activator 3 element, or both sites
      simultaneously indicated that both sites together are necessary and sufficient to
      control basal and PMA-induced activation of the human AT1 promoter in transfected
      VSMC. The capability of the phorbol ester PMA to activate the human AT1 promoter
      in VSMC via an AP-1 element suggests a prominent role for PKC/MAPK and Ets
      proteins in AT1 regulation.

PMID- 9277482
TI  - Induction of tetrahydrobiopterin synthesis in rat cardiac myocytes: impact on
      cytokine-induced NO generation.
AB  - Because tetra-hydrobiopterin (BH4) is an essential cofactor for nitric oxide (NO)
      formation, we investigated whether BH4 synthesis is required for cytokine-induced
      NO production in cultured rat cardiac myocytes. The total biopterin content of
      untreated cardiac myocytes was below our limit of detection. However, treatment
      with interleukin-1 alpha (IL-1 alpha) + interferon-gamma (IFN-gamma) caused a
      significant rise in biopterin levels and induced NO synthesis. 2,4-Diamino-6
      hydroxypyrimidine (DAHP), a selective inhibitor of GTP cyclohydrolase I (the rate
      limiting enzyme for de novo BH4 synthesis), completely abolished the elevation in
      biopterin levels induced by IL-1 alpha + IFN-gamma. DAHP also caused a
      concentration-dependent inhibition of (IL-1 alpha + IFN-gamma)-induced NO
      synthesis. Similarly, N-acetylserotonin, an inhibitor of the BH4 synthetic enzyme
      sepiapterin reductase, blocked increases in biopterin levels as well as NO
      synthesis induced by IL-1 alpha + IFN-gamma. Sepiapterin, substrate for BH4
      synthesis via the pterin salvage pathway, prevented this inhibition by DAHP or N
      acetylserotonin, and this effect was blocked by methotrexate. Sepiapterin and, to
      a lesser extent, BH4 dose dependently enhanced (IL-1 alpha + IFN-gamma)-induced
      NO synthesis, suggesting that the concentration of BH4 limits the rate of NO
      production. Inducible NO synthase mRNA and GTP cyclohydrolase I mRNA were induced
      by IL-1 alpha + IFN-gamma in parallel. We thus demonstrate that BH4 synthesis is
      an absolute requirement for induction of NO synthesis by cytokines in cardiac
      myocytes.

PMID- 9277483
TI  - Purification, characterization, and localization of two ATP diphosphohydrolase
      isoforms in bovine heart.
AB  - Two ATP diphosphohydrolase (ATPDase) isoforms have been purified from the bovine
      heart ventricle. The purification procedure includes the following steps:
      differential centrifugation, sucrose cushion centrifugation, solubilization with
      Triton X-100, DEAE agarose ion exchange, and Affi-Gel blue-Sepharose and
      concanavalin A (con A)-Sepharose chromatographies. The purified enzyme has an
      optimum pH of catalysis of 7.5 and requires Ca2+ or Mg2+. The apparent Michaelis
      constant of the enzyme, with ADP as the substrate, is 29 microM, and the apparent
      maximal velocity is 1.6 mumol.min-1.mg protein-1. Substrate specificity, heat
      inactivation curves, and copurification of adenosinetriphosphatase (ATPase) and
      adenosinediphosphatase (ADPase) activities confirmed the identity of the purified
      enzyme as an ATPDase. In addition, polyacrylamide gel electrophoresis, under
      nondenaturing conditions, showed identical migration patterns for the protein
      involved in ATPase and ADPase activities. Western blot analysis, with an antibody
      that specifically recognizes the NH2-terminal sequence of pig pancreas ATPDase
      and specifically reacts with bovine and human ATPDases, showed cross-reactivity
      with the purified ATPDase isoforms from the bovine heart. Immunocytochemical
      localization in the ventricle produced strong reactions with the plasma membrane
      of Purkinje fiber cells and the majority of myocardial cells. Immunoreactivity
      was variable, producing a mosaic-like aspect. As expected, smooth muscle cells
      and endothelial cells of coronary vessels were highly reactive. This ectoenzyme
      could play a protective role against the potentially deleterious effects of
      extracellular ATP. In tandem with 5'-nucleotidase, it produces adenosine, a
      powerful vasodilator, especially in hypoxic or ischemic conditions that favor the
      release of ATP.

PMID- 9277484
TI  - Near-infrared monitoring of cerebral tissue oxygen saturation and blood volume in
      newborn piglets.
AB  - Near-infrared spectrophotometry (NIRS) potentially provides a tool for
      noninvasive tissue oxygenation and blood volume monitoring. Cerebral monitoring
      could be useful in the prevention of hypoxic ischemic brain injury in newborns.
      This study sought to validate such NIRS measurements in normoventilated,
      hypocapnic, and hypoxemic states in the brain of newborn piglets vs. arterial
      (SaO2) and sagittal sinus blood hemoglobin saturation (SssO2) and blood volume
      measurements with 99mTc-labeled erythrocytes. NIRS measurements of cerebral blood
      volume (CBV) were performed with both oxyhemoglobin and indocyanine green as
      tracers, and changes in CBV were monitored by following the change in the
      concentration of total hemoglobin (i.e., oxyhemoglobin + deoxyhemoglobin). NIRS
      CBV measurements did not correlate well with the radioactive measurements. NIRS
      measurements of oxygenation, however, correlated well with a weighted mean value
      of SaO2 and SssO2 (r = 0.90; P < 0.0001). Multiple linear regression of the
      oxygenation index (i.e., oxyhemoglobin - deoxyhemoglobin) on SaO2 and SssO2
      suggested that NIRS sees hemoglobin in tissue in a venous-to-arterial ratio of
      2:1. Therefore, in this study, NIRS reliably monitored changes in cerebral tissue
      oxygenation but not in CBV.

PMID- 9277485
TI  - Vascular endothelial growth factor increases microvascular permeability via a
      Ca(2+)-dependent pathway.
AB  - We tested the hypothesis that vascular endothelial growth factor (VEGF) increases
      microvascular permeability by increasing calcium influx into endothelial cells
      forming the vessel walls. We measured microvessel hydraulic conductivity (Lp) in
      isolated perfused MS-222-anesthetized frog mesenteric microvessels during
      perfusion with VEGF under conditions that attenuate calcium influx. VEGF
      increased Lp during a second successive perfusion in the same microvessel by 7.8
      fold, which was not significantly different from that brought about by an initial
      application of VEGF (5.0-fold). However, under depolarizing conditions, the
      increase in Lp was reduced from 11.1- to 5.6-fold when depolarized to -10 mV (58
      mM K+) and to 2.8-fold when depolarized to 0 mV (100 mM K+). Attenuating calcium
      influx by the addition of nickel ions resulted in a similar attenuation of the
      increase in Lp (from 13- to 2.5-fold). VEGF also increased the intracellular
      calcium concentration in endothelial cells of perfused microvessels as determined
      by measurement with fura 2. We therefore conclude that VEGF increases Lp by
      increasing calcium influx.

PMID- 9277486
TI  - Rate-dependent abbreviation of Ca2+ transient in rat heart is independent of
      phospholamban phosphorylation.
AB  - The mechanisms underlying the accelerated decline of the intracellular Ca2+
      transient that occurs in cardiac muscle when stimulation rate is increased have
      been investigated in ventricular myocytes from rat hearts. Increasing stimulation
      rate from 0.1 to 0.5 and 1 Hz decreased the time taken for the Ca2+ transient to
      decline from its peak to 50% of its peak value in cells generating action
      potentials, when the duration of depolarization was held constant by voltage
      clamp, and when Na/Ca exchange was inhibited. The sarcoplasmic reticulum Ca2+
      adenosinetriphosphatase inhibitor thapsigargin inhibited rate-dependent
      abbreviation of the Ca2+ transient. However, neither a chemical inhibitor of
      Ca(2+)-calmodulin-dependent protein kinase II (KN62) nor a peptide inhibitor of
      this enzyme (calmodulin-binding domain peptide) had a significant effect on rate
      dependent abbreviation of the Ca2+ transient. Analysis of the phosphorylation of
      the regulatory sites Ser16 and Thr17 of phospholamban showed no significant
      change in phosphorylation with changes of stimulation rate. These data suggest
      that rate-dependent shortening of the Ca2+ transient is due predominantly to
      enhanced Ca2+ uptake by the sarcoplasmic reticulum without changes in
      phospholamban phosphorylation.

PMID- 9277487
TI  - Adenylyl cyclase and G protein receptor kinase expression during development of
      heart failure.
AB  - We examined alterations in left ventricular (LV) G protein receptor kinase (GRK)
      and adenylyl cyclase (AC) isoform expression during the development of pacing
      induced congestive heart failure (CHF). AC isoform and GRK expression were
      assessed 4 (mild CHF) and 28 (severe CHF) days after initiation of pacing. LV
      beta-adrenergic receptor (beta-AR) number and G protein content were unchanged by
      mild CHF. LV AC isoform mRNA content was unaltered by mild CHF, but there were
      increases in total GRK activity (P < 0.01), total GRK5 protein content (P <
      0.04), and GRK5 mRNA (P = 0.003); total GRK2 protein content and GRK2 mRNA were
      unchanged. Mild CHF was associated with decreased beta-AR coupling (P < 0.01) and
      reduced beta-AR stimulation of AC (P < 0.05). Severe CHF was associated with LV
      beta-AR downregulation (P = 0.0001) and uncoupling (P < 0.001) and marked
      generalized reduction of AC activity (mean P = 0.01). LV ACVI isoform mRNA
      content was reduced (P = 0.002), but ACII and ACV isoform mRNA contents were
      unaffected. Persistent elevations in LV total GRK activity (P < 0.01), total GRK5
      protein content (P < 0.001), and GRK5 mRNA (P = 0.01) were found; in contrast,
      total GRK2 protein content was unchanged and GRK2 mRNA was reduced (P = 0.02).
      These studies indicate that increased GRK activity is an early charge in heart
      failure that predates alterations in AC isoform expression. Impaired hormonal
      stimulation of AC, associated with beta-AR uncoupling, may result from increased
      GRK5 expression. AC downregulation is isoform specific and accompanies severe but
      not mild CHF.

PMID- 9277488
TI  - Inhibition of tetrahydrobiopterin biosynthesis impairs endothelium-dependent
      relaxations in canine basilar artery.
AB  - Tetrahydrobiopterin is an essential cofactor in biosynthesis of nitric oxide. The
      present study was designed to determine the effect of decreased intracellular
      tetrahydrobiopterin levels on endothelial function of isolated cerebral arteries.
      Blood vessels were incubated for 6 h in minimum essential medium (MEM) in the
      presence or absence of a GTP cyclohydrolase I inhibitor, 2,4-diamino-6
      hydroxypyrimidine (DAHP, 10(-2) M). Rings with and without endothelium were
      suspended for isometric force recording in the presence of a cyclooxygenase
      inhibitor, indomethacin (10(-5) M). In arteries with endothelium, DAHP
      significantly reduced intracellular levels of tetrahydrobiopterin. DAHP in
      combination with a precursor of the salvage pathway of tetrahydrobiopterin
      biosynthesis, sepiapterin (10(-4) M), not only restored but increased levels of
      tetrahydrobiopterin above control values. In DAHP-treated arteries, endothelium
      dependent relaxations to bradykinin (10(-10)-10(-6) M) or calcium ionophore
      A23187 (10(-9)-10(-6) M) were significantly reduced, whereas endothelium
      independent relaxations to a nitric oxide donor, 3-morpholinosydnonimine (10(-9)
      10(-4) M), were not affected. When DAHP-treated arteries with endothelium were
      incubated with sepiapterin (10(-4) M) or superoxide dismutase (150 U/ml),
      relaxations to bradykinin and A23187 were restored to control levels. In
      contrast, superoxide dismutase did not affect endothelium-dependent relaxations
      in arteries incubated in MEM. A nitric oxide synthase inhibitor, NG-nitro-L
      arginine methyl ester (10(-4) M), abolished relaxations to bradykinin or A23187
      in control arteries and in DAHP-treated arteries. These studies demonstrate that
      in cerebral arteries, decreased intracellular levels of tetrahydrobiopterin can
      reduce endothelium-dependent relaxations. Production of superoxide anions during
      activation of dysfunctional endothelial nitric oxide synthase appears to be
      responsible for the impairment of endothelial function.

PMID- 9277489
TI  - Early and delayed preconditioning: differential mechanisms and additive
      protection.
AB  - The purposes of this study were to determine whether 1) 24-h endotoxin (ETX)
      pretreatment induces delayed ("second window") myocardial protection against
      ischemia-reperfusion (I/R), 2) acute adenosine (Ado) or phenylephrine (PE)
      pretreatment confers similar protection, 3) the mechanisms of Ado- and PE-induced
      early protection remain intact after endotoxemia, 4) Ado- and PE-induced
      protection may combine with ETX-induced delayed protection to optimize cardiac
      protection, and 5) these strategies of early and/or delayed myocardial protection
      require de novo protein synthesis. Rats (n = 6-8/group) were treated with ETX
      (0.5 mg/kg i.p.) or vehicle, with or without prior inhibition of protein
      synthesis. Twenty-four hours later, the hearts were isolated, perfused, and
      acutely pretreated with Ado or PE before I/R (20-min ischemia and 40-min
      reperfusion). Developed pressure, coronary flow, compliance (end-diastolic
      pressure), and reperfusion creatine kinase leak were measured. Results indicated
      that 1) Ado, PE, and ETX independently induced myocardial functional protection;
      2) either Ado or PE acutely enhanced ETX induced protection; and 3) cycloheximide
      abolished delayed, but not acute, protection. We conclude that early and delayed
      forms of protection 1) may be combined to optimize protection and 2)
      differentially rely on de novo protein synthesis.

PMID- 9277490
TI  - Sympathetic nervous system and hypertension during prolonged TxA2/PGH2 receptor
      activation in rats.
AB  - The thromboxane A2 (TxA2)/prostaglandin H2 (PGH2) receptor mimetic U-46619 (0.6
      microgram.kg-1.min-1) was infused into conscious rats receiving a high-salt diet.
      U-46619 increased the mean arterial pressure (MAP) over 13 days by 25 +/- 2 mmHg,
      whereas the MAP of vehicle-infused controls did not change (-2 +/- 2 mmHg). In
      subgroups infused with U-46619, cardiac output was unchanged, whereas renal blood
      flow was reduced (before: 8.5 +/- 0.8; day 4: 5.7 +/- 0.7 ml/min; P < 0.01).
      Ifetroban (a specific TxA2/PGH2 receptor antagonist) reduced MAP to basal levels
      in the group receiving U-46619 when infused intravenously (1-100 micrograms/kg)
      but not intracerebroventricularly (1-100 ng/kg). Hexamethonium (10 mg/kg i.v., a
      ganglionic blocking agent) and prazosin (0.1 mg/kg, an alpha-adrenergic
      antagonist) decreased MAP significantly (P < 0.05) more in the experimental group
      (hexamethonium, U-46619: -55 +/- 3 vs. vehicle: -43 +/- 4 mmHg; and prazosin, U
      46619: 28 +/- 3 vs. vehicle: 17 +/- 2 mmHg). In conclusion, hypertension during
      prolonged infusions of U-46619 into conscious, salt-loaded rats is accompanied by
      an increase in total and renal vascular resistance and is dependent on peripheral
      but not central TxA2/PGH2 receptors and on the autonomic and alpha 1-adrenergic
      peripheral sympathetic nervous systems.

PMID- 9277492
TI  - Effect of nitric oxide synthase inhibitors on basal microvessel permeability and
      endothelial cell [Ca2+]i.
AB  - We evaluated the role of basal nitric oxide (NO) release in the regulation of
      microvessel permeability under resting conditions. We measured changes in
      microvessel hydraulic conductivity (Lp) and endothelial cytoplasmic calcium
      concentration ([Ca2+]i) after application of NO synthase (NOS) inhibitors to the
      lumen of individually perfused frog mesenteric venular microvessels. NOS
      inhibitors caused a transient increase in Lp. The mean ratios of peak test Lp
      values relative to control values in the presence of N omega-nitro-L-arginine
      methyl ester (L-NAME) at concentrations of 1, 10, and 100 microM were 2.5 +/-
      0.6, 2.9 +/- 0.7, and 4.8 +/- 0.4, respectively. N omega-monomethyl-L-arginine (L
      NMMA) showed a similar effect and a biologically inactive isomer of L-NMMA, D
      NMMA, showed no effect. These results demonstrate that basal levels of NO play a
      role in modulating microvessel permeability different from that due to NO
      produced in response to inflammatory agents. In the activated state NOS
      inhibitors attenuated the increased microvessel permeability in response to
      ionomycin and ATP [P. He, B. Liu, and F. E. Curry. Am. J. Physiol. 272 (Heart
      Circ. Physiol. 41): H176-H185, 1997]. The transient increase in basal
      permeability induced by NOS inhibitors was not accompanied by an increase in
      endothelial cell [Ca2+]i and did not require the presence of extracellular
      calcium. Application of ketotifen, a mast cell stabilizer, and an iron-chelating
      reagent, deferoxamine mesylate, attenuated the transient increase in Lp induced
      by L-NMMA, suggesting that basal NO may have an important antioxidant role in
      regulating normal permeability.

PMID- 9277491
TI  - Regulation of P-selectin expression in human endothelial cells by nitric oxide.
AB  - P-selectin translocation to the surface of endothelial cells is increased after
      exposure to the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl
      ester (L-NAME), resulting in increased endothelial adhesiveness. L-NAME (3 mM)
      was added to human cultured iliac vein endothelial cells for 1, 2, 4, and 6 h,
      and P-selectin mRNA expression was quantified by a ribonuclease protection assay.
      In parallel experiments, the NO donor, SPM-5185 (10 microM), was added to human
      iliac venous endothelial cells, and P-selectin mRNA expression quantified. P
      selectin protein synthesis was quantified by Western blot analysis. L-NAME caused
      increased expression of P-selection RNA at 2-4 h, whereas D-NAME, the
      stereoisomer lacking NO synthase-inhibitory activity, had no effect. The
      stimulatory effect of L-NAME was reversed by addition of 3 mM L-arginine. SPM
      5185 decreased P-selectin mRNA over the same time period (P < 0.02). The
      increased P-selectin mRNA expression induced by L-NAME was paralleled by an
      increase in P-selectin protein synthesis. The effects of SPM-5185 and L-arginine
      were also paralleled by decreases in P-selectin protein synthesis and in
      decreased adherence of human neutrophils to human iliac venous endothelial cells.
      The peak effect of inhibition of NO synthesis or addition of exogenous NO
      occurred at 2-4 h. These results suggest a regulatory effect of NO on endothelial
      P-selectin expression that modulates early leukocyte-endothelial cell
      interactions to preserve vascular homeostasis.

PMID- 9277493
TI  - Phosphorylation potential, adenosine formation, and critical PO2 in stimulated
      rat cardiomyocytes.
AB  - This study investigated the relationship between O2 consumption (VO2) and energy
      status in isolated rat cardiomyocytes using a system in which O2 supply (PO2) was
      maintained constant. For this purpose, VO2, phosphocreatine, ATP, intracellular
      pH, and adenosine of quiescent and stimulated cardiomyocytes were measured while
      the ambient PO2 was clamped between 0.1 and 120 mmHg. In quiescent cardiomyocytes
      (VO2: 7.9 +/- 1.2 nmol.min-1.mg protein-1), the threshold below which respiration
      decreased (critical PO2) was 1.4 mmHg. Above this value, energy status remained
      constant; below 1 mmHg, both free ADP and adenosine increased. Stimulation
      increased VO2 threefold and shifted the critical PO2 to 10 mmHg. Above this
      value, free ADP and adenosine remained unchanged; between 10 and 5 mmHg. VO2 was
      reduced but this did not change free ADP or adenosine. These findings demonstrate
      that 1) under well-oxygenated conditions (PO2 > 10 mmHg), VO2 is not controlled
      by ADP; 2) similarly, the adenosine formation is independent of VO2; a PO2 < 5
      mmHg is a prerequisite for enhanced adenosine formation; and 3) when O2 supply
      becomes limiting, ATP consumption is downregulated without measurable changes in
      energy status (hibernation).

PMID- 9277494
TI  - Electrotonic modulation of electrical activity in rabbit atrioventricular node
      myocytes.
AB  - Electrotonic effects of electrically coupling atrioventricular (AV) nodal cells
      to each other and to real and passive models of atrial and ventricular cells were
      studied using a technique that does not require functional gap junctions.
      Membrane potential was measured in each cell using suction pipettes. Mutual
      entrainment of two spontaneously firing AV nodal cells was achieved with a
      junctional resistance (Rj) of 500 M omega, which corresponds to only 39
      junctional channels, assuming a single-channel conductance of 50 pS. Coupling of
      AV nodal and atrial cells at Rj of 50 M omega caused hyperpolarization of the
      nodal cell, decreasing its action potential duration and either slowing or
      blocking diastolic depolarization in the AV node myocyte. Opposite changes
      occurred in the atrial action potential. When AV nodal and ventricular cells were
      coupled at Rj of 50 M omega, nodal diastolic potential was markedly
      hyperpolarized and diastolic depolarization was completely blocked with little
      change in ventricular diastolic potential. However, coupling did elicit marked
      changes in the action potential duration of both cells, with prolongation in the
      nodal cell and shortening in the ventricular cell. Nodal maximum upstroke
      velocity was increased by both atrial and ventricular coupling, as expected from
      the hyperpolarization that occurred. With an Rj of 50 M omega, spontaneous firing
      was blocked in all single AV nodal pacemaker cells during coupling to a real or
      passive model of an atrial or ventricular cell. These results demonstrate that
      action potential formation and waveform in a single AV nodal cell is
      significantly affected by electrical coupling to other myocytes.

PMID- 9277495
TI  - Systemic hemodynamic determinants of blood pressure in women: age, physical
      activity, and hormone replacement.
AB  - We tested the hypothesis that the age-related changes in systemic hemodynamic
      determinants of arterial blood pressure in healthy women are related to physical
      activity and hormone replacement status. We studied 66 healthy, normotensive
      premenopausal (21-35 yr) and postmenopausal (50-72 yr) sedentary and endurance
      trained women under supine resting conditions. Mean blood pressure was 7 mmHg
      higher in sedentary post- compared with premenopausal women, which was associated
      with an 11-mmHg higher systolic blood pressure, a 25% lower stroke volume and
      cardiac output, and a 50% higher systemic vascular resistance (all P < 0.05).
      Absolute (ml) levels of total blood volume did not differ across age, but resting
      oxygen consumption was approximately 35% lower in the postmenopausal women (P <
      0.05). The elevations in mean and systolic blood pressures with age were similar
      in endurance-trained runners, but, in contrast to the sedentary women, the
      elevations were not associated with significant age-related differences in
      cardiac output, stroke volume, or oxygen consumption, and only a modest (15%)
      increase in systemic vascular resistance (P = 0.06). Postmenopausal swimmers
      demonstrated the same systemic hemodynamic profile as that of postmenopausal
      runners, indicating a nonspecific influence of the endurance-trained state. Blood
      pressure and its systemic hemodynamic determinants did not differ in
      postmenopausal users compared with those of nonusers of hormone replacement
      therapy. Resting oxygen consumption was the strongest physiological correlate of
      cardiac output in the overall population (r = 0.65, P < 0.001). We conclude that
      1) the increases in arterial blood pressure at rest with age in healthy
      normotensive women are not obviously related to habitual physical activity
      status; 2) the systemic hemodynamic determinants of the age-related elevations in
      blood pressure are fundamentally different in sedentary vs. active women,
      possibly due, in part, to an absence of decline in resting oxygen consumption in
      the latter; and 3) systemic hemodynamics at rest are not different in healthy
      normotensive postmenopausal users vs. nonusers of estrogen-based hormone
      replacement.

PMID- 9277496
TI  - Frequency-response characteristics of autonomic nervous system function in
      conscious rats.
AB  - To characterize the efferent pathway from the hypothalamic paraventricular
      nucleus (PVN) to peripheral autonomic neurons and finally to selected effector
      organs, we stimulated the PVN in 10 conscious rats at frequencies ranging from
      0.05 to 2.0 Hz. Simultaneously, blood pressure, heart rate, splanchnic
      sympathetic nerve activity, and mesenteric artery blood flow were measured. The
      sinus node of the heart responded to PVN stimulation via the parasympathetic
      pathway (during beta 1-adrenergic blockade) up to a stimulation frequency of 2.0
      Hz, whereas the sympathetically mediated response (during muscarinic blockade)
      was limited to stimulation frequencies < 0.5 Hz. The splanchnic nerve responded
      to PVN stimulation with synchronous discharges up to stimulation frequencies of
      2.0 Hz, whereas the oscillatory component of the vasoconstrictor response of the
      mesenteric artery was negligible beyond stimulation frequencies of 1.0 Hz. We
      conclude that sympathetic transmission to the heart is at least four times slower
      than parasympathetic transmission. In addition, the time-limiting step in
      sympathetic transmission from the hypothalamus to vascular smooth muscle
      contraction and pacemaker activity of the sinus node may be located at the site
      of synaptic transmission to the adrenergic receptors.

PMID- 9277497
TI  - Ryanodine receptor dysfunction in porcine stunned myocardium.
AB  - We investigated the effects of myocardial stunning on the function of the two
      main Ca2+ transport proteins of the sarcoplasmic reticulum (SR), the Ca(2+)
      adenosinetriphosphatase and the Ca(2+)-release channel or ryanodine receptor.
      Regional myocardial stunning was induced in open-chest pigs (n = 6) by a 10-min
      occlusion of the left anterior descending coronary artery (LAD) and 2 h
      reperfusion. SR vesicles isolated from the LAD-perfused region (stunned) and the
      normal left circumflex coronary artery (LC)-perfused region were used to assess
      the oxalate-supported 45Ca2+ uptake, [3H]ryanodine binding, and single-channel
      recordings of ryanodine-sensitive Ca(2+)-release channels in planar lipid
      bilayers. Myocardial stunning decreased LAD systolic wall thickening to 20% of
      preischemic values. The rate of SR 45Ca2+ uptake in the stunned LAD bed was
      reduced by 37% compared with that of the normal LC bed (P < 0.05). Stunning was
      also associated with a 38% reduction in the maximal density of high-affinity
      [3H]ryanodine binding sites (P < 0.05 vs. normal LC) but had no effect on the
      dissociation constant. The open probability of ryanodine-sensitive Ca(2+)-release
      channels determined by single channel recordings in planar lipid bilayers was 26
      +/- 2% for control SR (n = 33 channels from 3 animals) and 14 +/- 2% for stunned
      SR (n = 21 channels; P < 0.05). This depressed activity of SR function observed
      in postischemic myocardium could be one of the mechanisms underlying myocardial
      stunning.

PMID- 9277498
TI  - Differing sympathetic and vagal effects on atrial fibrillation in dogs: role of
      refractoriness heterogeneity.
AB  - Although sympathetic activation is believed to promote atrial fibrillation (AF),
      the effects of sympathetic stimulation on AF have not been systematically
      studied. In seven morphine-chloralose-anesthetized dogs, autonomic
      decentralization increased atrial effective refractory period (ERP) and reentrant
      wavelength (WL) and decreased the duration of AF induced by burst atrial pacing.
      Graded bilateral stellate ansa stimulation decreased ERP and WL to values similar
      to those before decentralization but did not return AF duration to
      predecentralization values. Sympathetic and bilateral vagal stimulation were
      adjusted in six additional dogs to produce similar effects on ERP and WL. Despite
      comparable effects on mean WL, the duration of AF was increased by vagal
      stimulation from 14 +/- 5 (control) to 372 +/- 96 s (P < 0.001) but was not
      altered significantly (26 +/- 10 s) by sympathetic stimulation. Vagal stimulation
      increased the variability in atrial refractoriness, as indicated by the standard
      deviation of ERP at seven atrial sites and of activation frequency during AF at
      112 recording sites, whereas sympathetic stimulation had no significant effect on
      these indexes of ERP heterogeneity. We conclude that sympathetic stimulation is
      much less effective than vagal stimulation in promoting AF and that heterogeneity
      in atrial ERP may be important in determining the ability to sustain AF.

PMID- 9277500
TI  - Role of ET and NO in resuscitative effect of diaspirin cross-linked hemoglobin
      after hemorrhage in rat.
AB  - Diaspirin cross-linked hemoglobin (DCLHb) is a hemoglobin-based therapeutic agent
      that produces significant cardiovascular effects, possibly due to its actions on
      vasoactive substances, such as endothelin (ET) and nitric oxide (NO). We have
      studied the modulation of cardiovascular effects of DCLHb by an NO synthase
      inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), and an ETA-receptor
      antagonist, FR-139317, in hemorrhaged rats. Control rats resuscitated with
      vehicle [Ringer lactate (RL), 4 ml/kg iv] did not show any improvement in O2
      consumption, base deficit, systemic hemodynamics, or regional blood flow after
      hemorrhage, and the rats survived for < 70 min. Administration of DCLHb (400
      mg/kg iv) significantly improved O2 consumption, base deficit, systemic
      hemodynamics, and regional blood circulation after resuscitation, and the rats
      survived for > 120 min after hemorrhage. Plasma ET-1 and guanosine 3',5'-cyclic
      monophosphate (cGMP) concentrations increased after hemorrhage. DCLHb produced an
      increase in ET-1 and decreased cGMP concentrations in plasma. Pretreatment with L
      NAME (10 mg/kg iv) or FR-139317 (4 mg/kg iv) attenuated the DCLHb-induced
      improvement in survival time, base deficit, systemic hemodynamics, and regional
      blood circulation. L-NAME (10 mg/kg iv) per se did not produce any resuscitative
      effect; therefore the NO mechanism may not be contributing toward the efficacy of
      DCLHb in hemorrhaged rats. However, FR-139317 attenuated the efficacy of DCLHb;
      therefore an increase in plasma ET-1 concentration by DCLHb may be contributing
      toward the efficacy of DCLHb in hemorrhage. Hemorrhage-induced increase in cGMP
      levels could be attenuated by L-NAME, but L-NAME was not effective in
      resuscitation of hemorrhaged rats, indicating a lack of role of NO in
      resuscitation. It is concluded that the ET mechanism is more important in the
      beneficial effect of DCLHb than the NO mechanism in hemorrhage.

PMID- 9277499
TI  - Distinct mechanisms for N-acetylcysteine inhibition of cytokine-induced E
      selectin and VCAM-1 expression.
AB  - We have examined the effects of N-acetyl-L-cysteine (NAC), a well-characterized,
      thiol-containing antioxidant, on agonist-induced monocytic cell adhesion to
      endothelial cells (EC). NAC inhibited interleukin-1 (IL-1 beta)-induced, but not
      basal, adhesion with 50% inhibition at approximately 20 mM. Monocytic cell
      adhesion to EC in response to tumor necrosis factor-alpha (TNF-alpha),
      lipopolysaccharide (LPS), alpha-thrombin, or phorbol 12-myristate 13-acetate
      (PMA) was similarly inhibited by NAC. Unlike published studies with
      pyrrolidinedithiocarbamate, which specifically inhibited vascular cell adhesion
      molecule 1 (VCAM-1), NAC inhibited IL-1 beta-induced mRNA and cell surface
      expression of both E-selectin and VCAM-1. NAC had no effect on the half-life of E
      selectin or VCAM-1 mRNA. Although NAC reduced nuclear factor-kappa B (NF-kappa B)
      activation in EC as measured by gel-shift assays using an oligonucleotide probe
      corresponding to the consensus NF-kappa B binding sites of the VCAM-1 gene (VCAM
      NF-kappa B), the antioxidant had no appreciable effect when an oligomer
      corresponding to the consensus NF-kappa B binding site of the E-selectin gene (E
      selectin-NF-kappa B) was used. Because NF-kappa B has been reported to be redox
      sensitive, we studied the effects of NAC on the EC redox environment. NAC caused
      an expected dramatic increase in the reduced glutathione (GSH) levels in EC. In
      vitro studies demonstrated that whereas the binding affinity of NF-kappa B to the
      VCAM-NF-kappa B oligomer peaked at a GSH-to-oxidized glutathione (GSSG) ratio of
      approximately 200 and decreased at higher ratios, the binding to the E-selectin
      NF-kappa B oligomer appeared relatively unaffected even at ratios > 400, i.e.,
      those achieved in EC treated with 40 mM NAC. These results suggest that NF-kappa
      B binding to its consensus sequences in the VCAM-1 and E-selectin gene exhibits
      marked differences in redox sensitivity, allowing for differential gene
      expression regulated by the same transcription factor. Our data also demonstrate
      that NAC increases the GSH-to-GSSG ratio within the EC suggesting one possible
      mechanism through which this antioxidant inhibits agonist-induced monocyte
      adhesion to EC.

PMID- 9277501
TI  - Na+/Ca2+ exchange current and contractions measured under Cl(-)-free conditions
      in developing rabbit hearts.
AB  - Previous studies suggesting a greater functional role of cardiac Na+/Ca2+
      exchange at birth were performed using tightly buffered free cytosolic Ca2+
      concentration ([Ca2+]i). Because Na+/Ca2+ exchange current (INaCa) is influenced
      by physiological fluctuations in [Ca2+]i, we used conditions of minimally
      buffered [Ca2+]i to simultaneously record INaCa and cell contractions in single
      ventricular myocytes isolated from 1 to 27-day-old and adult rabbits. With
      conventional Cl(-)-containing solutions. Ni(2+)-sensitive outward and inward
      charge movements were unbalanced, suggesting the presence of a contaminating
      current (presumably the Ca(2+)-activated Cl- current). Removing Cl- abolished
      this discrepancy in all age groups and allowed for the accurate quantitation of
      INaCa. Under Cl(-)-free conditions, outward and inward charge movements were high
      at birth (4 days: 0.42 +/- 0.03 and -0.38 +/- 0.04 pC/pF, respectively) and
      decreased postnatally (adult: 0.08 +/- 0.01 and -0.07 +/- 0.01 pC/pF,
      respectively). Newborn but not adult myocytes contracted during depolarizations
      in the presence of nifedipine, ryanodine, and thapsigargin. The magnitudes of
      outward charge movement (Ca2+ influx) and cell shortening exhibited similar
      voltage dependence, consistent with INaCa-mediated contractions. These results
      indicate that INaCa can directly support contraction in newborn rabbit
      ventricular myocytes.

PMID- 9277502
TI  - Protein kinase C-mediated preconditioning of cardiac myocytes: role of adenosine
      receptor and KATP channel.
AB  - Activation of the adenosine receptor, protein kinase C (PKC), and the ATP
      sensitive potassium (KATP) channel is known to induce preconditioning. The
      objective here was to determine the signaling role of the adenosine receptor,
      PKC, and the KATP channel and the temporal sequence of activation of these three
      mediators in preconditioning of cardiac myocytes. Chick embryo ventricular
      myocytes were used as a myocyte model of preconditioning. Brief hypoxic or
      adenosine exposure preconditioned the myocytes, and the PKC inhibitors
      chelerythrine or calphostin C blocked this preconditioning effect, suggesting
      that PKC is an effector distal to the adenosine receptor in initiating the
      hypoxia- or adenosine-induced preconditioning. The PKC activator phorbol 12
      myristate 13-acetate (PMA), but not the inactive phorbol 4 alpha-phorbol [2,13
      didecanoate or 4 alpha-phorbol 12-myristate 13-acetate, could precondition the
      myocyte; the PMA-induced preconditioning effect was blocked by chelerythrine or
      calphostin C. Glibenclamide or 5-hydroxydecanoate, when present during a 5-min
      exposure to PMA or a 90-min hypoxic period, blocked the PMA-induced
      preconditioning. However, the presence of 8-sulfophenyltheophylline during
      exposure to PMA failed to block the PMA-induced preconditioning, whereas 8
      sulfophenyltheophylline was able to abolish this preconditioning effect when
      added during the 90-min hypoxic period. The data provide direct evidence that the
      KATP channel, not the adenosine receptor, is the effector down-stream from PKC in
      initiating PKC-mediated preconditioning. Both the adenosine receptor and KATP
      channel are required to exert the actual protective effect during the sustained
      hypoxia.

PMID- 9277503
TI  - Reperfusion-induced leukocyte adhesion and vascular protein leakage in normal and
      hypercholesterolemic rats.
AB  - The objective of this study was to define the influence of hypercholesterolemia
      on ischemia-reperfusion (I/R)-induced leukocyte-endothelial cell adhesion and
      albumin leakage in rat mesenteric venules. The microvascular alterations normally
      elicited by I/R (leukocyte adherence and emigration, albumin leakage, and
      platelet aggregation) were more pronounced in hypercholesterolemic rats (compared
      with control rats). Monoclonal antibodies against the adhesion glycoproteins
      CD11/CD18 and intercellular adhesion molecule-1 attenuated the I/R-induced
      leukocyte adherence and emigration and albumin leakage. Leukocyte adherence, but
      not albumin leakage, was diminished in animals pretreated with a P-selectin
      specific antibody. Platelet aggregation was reduced by antibodies directed
      against either P-selectin, CD18, or intercellular adhesion molecule-1, as well as
      a GPIIb-IIIa antagonist. These results indicate that the enhanced reperfusion
      induced albumin leakage in hypercholesterolemic rats is dependent on leukocyte
      endothelial cell adhesion. Furthermore, P-selectin- and CD11/CD18-dependent
      heterotypic and GPIIb-IIIa-mediated homotypic platelet aggregation appear to
      influence the extravasation of both leukocytes and albumin in postischemic
      venules of hypercholesterolemic rats.

PMID- 9277504
TI  - Delayed preconditioning of cultured adult rat cardiac myocytes: role of 70- and
      90-kDa heat stress proteins.
AB  - We investigated the protective effect of heat stress and metabolic
      preconditioning in cultured adult rat cardiac myocytes and correlated this effect
      with induction of heat shock proteins (HSP). Myocytes were preconditioned with
      sublethal heat shock or metabolic preconditioning for 30 min. Twenty hours later,
      preconditioned myocytes were subjected to lethal heat shock (46 degrees C for 2
      h) or ischemia by incubation in ischemic buffer for 2 h. Cellular injury index
      was reduced from 69 +/- 4.0% in lethally heat-shocked cells to 27.0 +/- 1.6% with
      heat shock preconditioning (mean +/- SE; P < 0.01) and 19.0 +/- 3.0% with
      metabolic preconditioning (P < 0.01). Cellular injury index was 81.0 +/- 1.0% in
      ischemic myocytes and was reduced to 25.9 +/- 2.7 and 21.4 +/- 2.6% in heat shock
      and metabolic-preconditioned myocytes, respectively (P < 0.01). A significant
      cross-tolerance of myocytes against lethal injury was observed with the two
      preconditioning methods. Western blot analysis revealed 3.3- and 2.5-fold
      increases in HSP 90 and 500- and 15-fold increases in HSP 70 with heat shock and
      metabolic preconditioning, respectively. HSP 27 expression remained unaltered
      relative to control cells. We conclude that heat shock and metabolic
      preconditioning induce delayed tolerance against lethal injuries in adult cardiac
      myocytes with elevated levels of HSP 70 and HSP 90.

PMID- 9277505
TI  - Response of resistance arteries to reduced PO2 and vasodilators during
      hypertension and elevated salt intake.
AB  - This study assessed vasodilator responses in skeletal muscle resistance arteries
      (100-250 microns) from rats with chronic (4-8 wk) reduced renal mass (RRM)
      hypertension and normotensive sham-operated controls on a high (4% NaCl; HSSHAM)-
      or low (0.4% NaCl; LSSHAM)-salt diet. Arteries from RRM hypertensive rats [normal
      and high-salt diet (HSRRM)] and a separate group of spontaneously hypertensive
      rats exhibited an impaired dilation in response to reduced PO2 compared with
      those of their normotensive controls. Prostacyclin release, assessed by radio
      immunoassay for 6-ketoprostaglandin F1 alpha, increased significantly in response
      to reduced PO2, but was unaffected by hypertension or salt intake. Dilator
      responses to acetylcholine and the prostacyclin analog iloprost were
      significantly reduced in both HSRRM and HSSHAM compared with LSSHAM rats.
      Dilation in response to direct activation of adenylate cyclase with forskolin or
      guanylate cyclase with the nitric oxide donor sodium nitroprusside was not
      significantly different in HSRRM, HSSHAM, and LSSHAM rats. These results indicate
      that hypoxic dilation is impaired in skeletal muscle resistance arteries of
      hypertensive rats and that chronic high-salt diet alone leads to impaired
      vasodilator responses in resistance arteries of normotensive animals, possibly
      via abnormalities in membrane function or G protein signaling rather than
      impaired second-messenger function.

PMID- 9277506
TI  - Endothelium-dependent regulation of cerebrovascular tone by extracellular and
      intracellular ATP.
AB  - ATP receptors and ATP-sensitive potassium channels (KATP) are expressed in
      vascular smooth muscle (VSM) and endothelial cells (EC). In isolated penetrating
      vessels, ATP caused a dilatation when applied intraluminally but not
      extraluminally. The actions of ATP were blocked by the nitric oxide (NO)
      synthesis inhibitor N omega-nitro-L-arginine (0.1 mM) but were only reduced by N
      monomethyl-L-arginine (0.1 mM); responses to intraluminal ATP were also prevented
      by thapsigargin. The KATP opener (KCO) nicorandil (1 microM) caused an NO
      independent vasodilatation when applied extraluminally and an NO-dependent
      response when applied intraluminally. Both responses were blocked by
      glibenclamide. EC-mediated responses to nicroandil were prevented by blockade of
      guanylate cyclase by LY-83583 (10 microM). The effects of nicorandil were
      mimicked by pinacidil (1-10 microM). Exposure of the endothelium to 500 microM
      cyanide and 0 mM glucose ("in vitro ischemia") caused a vasodilatation that was
      reduced by exposure to glibenclamide (5 microM). Blockade of NO synthase produced
      similar effects, suggesting that the ischemic dilation is mediated by KATP and
      NO. Our results suggest that both VSM and EC mediate the vascular responses
      induced by KCOs, whereas the dilatation induced by intraluminal ATP is mediated
      by the endothelium. The endothelium-dependent component of the in vitro ischemic
      vasodilatation is mediated by opening of endothelial KATP and subsequent release
      of NO.

PMID- 9277507
TI  - Diastolic SR Ca efflux in atrial pacemaker cells and Ca-overloaded myocytes.
AB  - Evidence has shown that the sarcoplasmic reticulum (SR) of cardiac cells releases
      Ca not only during excitation-contraction coupling but also during diastole,
      albeit at a much lower rate. This diastolic SR Ca release (leak) has also been
      implicated in the generation of spontaneous depolarization in latent atrial
      pacemaker cells of the cat right atrium. In the present work, we sought to
      measure Ca transients in pacemaker and nonpacemaker cells of the cat using the
      fluorescent Ca indicator indo 1. Atrial latent pacemaker cells develop a slow Ca
      transient when rested in the presence of both Na- and Ca-free solution and
      thapsigargin [used to inhibit Na/Ca exchange and SR Ca adenosinetriphosphatase
      (Ca-ATPase), respectively]. This increase in cytosolic Ca concentration ([Ca]i)
      is probably caused by the rate of SR Ca leak exceeding the capacity of the
      remaining Ca transport systems (e.g., sarcolemmal Ca-ATPase and mitochondrial Ca
      uptake). However, neither cat sinoatrial (SA) node cells nor myocytes from cat
      atrium or ventricle exhibited a similar increase in [Ca]i during the same
      protocol. This indicates that SR Ca leak in these cells occurred at a rate low
      enough to be within the capacity of the slow Ca transporters, as observed
      previously in rabbit ventricular myocytes. When atrial and ventricular myocytes
      were stimulated at higher frequencies, sufficient to markedly increase diastolic
      and systolic [Ca]i and approach Ca overload (and spontaneous activity), they
      responded to inhibition of SR Ca-ATPase and Na/Ca exchange with a slow Ca
      transient similar to that normally observed in atrial latent pacemaker cells.
      Furthermore, the SR Ca depletion by thapsigargin did not affect spontaneous
      activity of SA node cells, but it prevented or slowed pacemaker activity in the
      atrial latent pacemaker cells. These findings suggest that enhanced diastolic SR
      Ca efflux contributes significantly to the generation of spontaneous activity in
      atrial subsidiary pacemakers under normal conditions and in Ca-overloaded
      myocytes but not in SA node cells.

PMID- 9277508
TI  - Effect of cocaine and methylecgonidine on intracellular Ca2+ and myocardial
      contraction in cardiac myocytes.
AB  - We evaluated the cardiac effects of the principle pyrolysis product of crack
      cocaine smoking, methylecgonidine (MEG), in comparison with cocaine. Peak cell
      shortening and intracellular Ca2+, as detected by the Ca2+ indicator indo 1, were
      recorded in enzymatically isolated ferret myocytes. Both cocaine and MEG
      decreased peak cell shortening and peak intracellular Ca2+ concentration
      ([Ca2+]i) in a dose-dependent manner (10(-8)-10(-4) M). MEG shifted the peak
      [Ca2+]i-to-peak shortening relationship downward and was more potent than
      cocaine. Atropine (10(-6) M) upwardly shifted the dose-response curves of MEG,
      cocaine, and carbachol but not of procaine. The negative inotropic effects of MEG
      were inhibited by methoctramine, a selective M2 receptor blocker but not by M1
      (pirenzepine) or M3 (4-diphenylacetoxy-N-methylpiperidine methiodide) blocking
      agents. In contrast to cocaine, the effects of large doses of MEG were
      irreversible over the time course of our experiments, raising the possibility of
      structural damage. We conclude that MEG acts primarily on M2 cholinergic
      receptors in the heart to produce acute cardiac intoxication and, in contrast to
      cocaine, may decrease the myofilament Ca2+ responseness and cause structural
      damage to myocytes by a direct toxic effect.

PMID- 9277509
TI  - Ischemic preconditioning of human myocardium: protein kinase C mediates a
      permissive role for alpha 1-adrenoceptors.
AB  - The purposes of this study were to determine whether ischemic preconditioning
      (IPC) in human atrial trabeculae is mediated by alpha 1-adrenoceptors and protein
      kinase C (PKC) and whether the protection of IPC is replicated with alpha 1
      adrenoceptor stimulation [alpha 1-adrenoceptor preconditioning (alpha 1-PC)].
      Atrial trabeculae were obtained during coronary bypass surgery. The trabeculae
      were suspended in organ baths containing Tyrode solution and field stimulated at
      1 Hz, and developed force was recorded. The trabeculae underwent 45 min of
      simulated ischemia (SI) and 120 min of reperfusion (I/R injury). IPC trabeculae
      received transient SI before I/R injury, alpha 1-Adrenoceptor blockade with BE
      2254 and PKC inhibition with chelerythrine were independently combined with IPC
      before I/R injury. alpha 1-PC before I/R was examined with alpha 1-adrenergic
      agonist (phenylephrine) pre-treatment. Improved recovery of developed force and
      higher tissue creatine kinase activity were present in IPC trabeculae, and the
      protective effect of IPC was eliminated with either alpha 1-adrenoceptor blockade
      or PKC inhibition. alpha 1-PC trabeculae also exhibited enhanced functional
      recovery after I/R injury but lacked preservation of tissue creatine kinase
      activity. PKC inhibition eliminated the functional protection of alpha 1-PC.
      These results suggest that, in human atrial trabeculae, alpha 1-adrenoceptors and
      PKC mediate, in part, the functional and tissue CK preservation conferred by IPC,
      but alpha 1-PC does not replicate the protection of IPC.

PMID- 9277510
TI  - Entrained ion transport systems generate the membrane component of chaotic
      agonist-induced vasomotion.
AB  - We have analyzed the contribution of membrane ion transport systems to chaotic
      vasomotion induced by histamine in isolated rabbit ear resistance arteries.
      Dynamic complexity was monitored as a fractal correlation dimension that provides
      an estimate of the minimum number of control variables contributing to an
      irregular time series and generally took a value between 2 and 4. A distinct
      subcomponent of the overall oscillatory activity (frequency approximately 0.06
      Hz) was selectively suppressed by blockade of Ca(2+)-activated K+ channels (KCa)
      with tetraethylammonium, Ca(2+)-activated Cl- channels with low extracellular Cl-
      concentration and niflumic acid, the Na(+)-K+ adenosine-triphosphatase (ATPase)
      with ouabain, and Na+/Ca2+ exchange with low-Na+ buffer. Each of these
      interventions caused a fall in average fractal dimension to a value < 2, whereas
      inhibition of voltage-dependent K+ channels with 4-aminopyridine or the Ca(2+)
      ATPase extrusion pump with vanadate were without effect on the form and
      complexity of the vasomotion. There was no systematic correlation between the
      changes in fractal dimension induced by the various interventions and their
      effects on perfusion pressure. Our findings suggest that nonlinearity in the
      kinetics of multiple coupled ion transport systems leads to entrainment and the
      emergence of a composite membrane oscillator, thus accounting for the low fractal
      dimension of the vasomotion observed in these arteries.

PMID- 9277511
TI  - Left atrial systolic and diastolic function after cessation of pacing in
      tachycardia-induced heart failure.
AB  - Studies in the rapid-pacing model of heart failure have shown that left
      ventricular (LV) systolic function normalizes on cessation of pacing and LV
      diastolic dysfunction persists, but there is no information regarding atrial
      function under these conditions. To determine the effects of cessation of pacing
      on left atrial (LA) systolic and diastolic function, ten dogs with rapid pacing
      induced heart failure (250 beats/min for 3-4 wk), six dogs with regression of
      heart failure (4 wk after cessation of rapid pacing), and seven control dogs were
      instrumented with LA sonomicrometers and micromanometers. At matched LA pressure,
      LA ejection (10.2 +/- 3.0 vs. 17.4 +/- 5.5%), reservoir volume fractions (19 +/-
      8 vs. 35 +/- 11%), and heart rate-corrected mean normalized systolic ejection
      rate (1.25 +/- 0.33 vs. 1.60 +/- 0.44 EF/s) were significantly less, and the
      volume-normalized diastolic stiffness constant (4.9 +/- 0.8 vs. 3.2 +/- 1.1) was
      significantly greater, in regression versus control dogs; these changes were
      associated with incomplete regression of LA hypertrophy and a persistent 77.4%
      increase in beta-myosin heavy chain (beta-MHC) in the LA body. LV systolic
      function and weight were not significantly different, whereas the time constant
      of LV relaxation was longer (52.5 +/- 4.4 vs. 40.8 +/- 7.6 ms; P < 0.05) and LV
      end-diastolic pressure was greater (12.2 +/- 1.8 vs. 7.1 +/- 2.0 mmHg; P < 0.05)
      in regression compared with control dogs. Thus, unlike the normalization of LV
      systolic function observed with cessation of rapid pacing, LA systolic function
      is persistently abnormal, owing in part to persistent LV diastolic dysfunction,
      residual LA hypertrophy, and MHC isoform switches.

PMID- 9277512
TI  - NO release and the opening of K+ATP channels mediate vasodilator responses to
      histamine in the cat.
AB  - Responses to histamine were investigated in the hindlimb vascular bed of the cat
      under constant-flow conditions. Injections of histamine, the H1 agonist HTMT, the
      H2 agonist dimaprit, and the H3 agonist R(-)-alpha-methylhistamine caused dose
      related decreases in hindlimb perfusion pressure. Pyrilamine reduced the
      responses to histamine and HTMT by approximately 80%, whereas cimetidine reduced
      the responses to histamine by 20% and to dimaprit by approximately 50%. The H3
      receptor antagonist thioperamide reduced the responses to R(-)-alpha
      methylhistamine by approximately 60% but was without effect on the other
      histamine agonists. These data suggest the presence of H1, H2, and H3 receptors
      in the hindlimb vascular bed of the cat, that histamine acts, for the most part,
      by stimulating H1 receptors, and that H3-receptor activation is not involved in
      mediating the responses to histamine. The responses to histamine and the H1-, H2
      , and H3-receptor agonists were significantly reduced by a nitric oxide synthase
      inhibitor and enhanced in duration by the guanosine 3', 5'-cyclic monophosphate
      (cGMP)-selective phosphodiesterase inhibitor zaprinast, suggesting that the
      responses are mediated, in part, by the release of nitric oxide and an increase
      in cGMP levels. The responses to histamine agonists but not to nitric oxide
      donors were significantly reduced by the nonselective K(+)-channel antagonist
      tetraethylammonium. The responses to histamine and the H1, H2, and H3 agonists
      were not affected by the cyclooxygenase inhibitor meclofenamate. The responses to
      histamine and HTMT are also reduced 30-50% by U-37883A, an ATP-sensitive K+
      (K+ATP)-channel antagonist, at a time when the responses to the H2 and H3
      agonists were unaltered. The present data suggest that vasodilation of the
      hindlimb vascular bed in response to H1-, H2-, and H3-receptor activation is
      mediated by a tetraethylammonium-sensitive mechanism that is associated with the
      release of nitric oxide and an increase in cGMP levels. These data further
      suggest that the response to H1-receptor activation is mediated by the
      complementary, yet independent, release of nitric oxide and the opening of a
      K+ATP channel.

PMID- 9277513
TI  - Pregnancy augments uteroplacental vascular endothelial growth factor gene
      expression and vasodilator effects.
AB  - This study examined a potential role for vascular endothelial growth factor
      (VEGF) in uterine artery remodeling and vasodilation during pregnancy. Reverse
      transcription-polymerase chain reaction (RT-PCR) was used to detect VEGF mRNA in
      uterine tissues from nonpregnant (NP), midpregnant (MP, 15-16 days), and late
      pregnant (LP, 19-21 days) rats and in placentas from MP and LP rats. VEGF mRNA
      levels in uteri and placentas were determined by Northern blotting, and the
      vasorelaxant activity of recombinant human VEGF (rh-VEGF) was tested and compared
      in isolated uterine arteries from LP and NP animals. VEGF120 and VEGF164 were the
      major isoforms detected in uterine tissues; all members of the VEGF family
      (VEGF120, VEGF164, VEGF188, and VEGF205) were expressed in LP placentas. VEGF
      mRNA levels increased 60% in MP and 80% in LP above those in NP (P < 0.05) in
      uterine tissues; VEGF mRNA levels were also detectable in placentas and elevated
      approximately fivefold in LP vs. MP tissues (P < 0.01). Phenylephrine
      preconstricted uterine arcuate arteries (NP and LP) dilated in response to
      rhVEGF, an effect that was completely abolished by endothelial denudation or
      pretreatment with genistein, a tyrosine kinase inhibitor. The magnitude of
      dilation to an intermediate concentration of rhVEGF (1 nM) was greater in LP than
      in NP vessels (55 +/- 8 vs. 24 +/- 11%; P < 0.05), and this effect was diminished
      comparably in both groups (approximately 60% by N omega-nitro-L-arginine, an
      inhibitor of nitric oxide synthesis. These results suggest that VEGF may play a
      role in the vascular remodeling and vasodilation that lead to decreased uterine
      vascular resistance and increased uterine blood flow during pregnancy.

PMID- 9277514
TI  - Disparate effects of preconditioning and MLA on 5'-NT and adenosine levels during
      coronary occlusion.
AB  - Ischemic preconditioning has been proposed to protect the heart against
      infarction by increasing 5'-nucleotidase (5'-NT) activities and augmenting
      adenosine levels during sustained coronary artery occlusion. To test this theory,
      anesthetized dogs received four 5-min episodes of preconditioning ischemia,
      pretreatment with the pharmacological "preconditioning mimetic" monophosphoryl
      lipid A (MLA, 35 micrograms/kg i.v.) or no intervention before coronary artery
      ligation. At 20 min into occlusion (the crucial time at which myocyte death
      begins in this model), myocardial samples were obtained for measurement (by high
      performance liquid chromatography) of ectosolic and cytosolic 5'-NT activity and
      adenosine levels. Preconditioning and MLA pretreatment limit infarct size in the
      canine model by 75 and 50%, respectively. However, only MLA augmented 5'-NT
      activity [i.e., cytosolic 5'-NT in the ischemic subendocardium was 26 +/- 1, 39
      +/- 7, and 26 +/- 6 nmol. mg protein-1. min-1 in preconditioned, MLA, and control
      groups (P < 0.05), respectively]. Moreover, adenosine levels (in nmol/mg protein)
      were increased with MLA treatment (2.30 +/- 0.44) but attenuated in
      preconditioned dogs (1.11 +/- 0.23; P < 0.05) versus controls (1.87 +/- 0.29).
      Thus 5'-NT and adenosine levels need not be increased beyond control values
      during sustained occlusion to elicit cardioprotection.

PMID- 9277515
TI  - Contribution of chondroitin-dermatan sulfate-containing proteoglycans to the
      function of rat mesenteric arteries.
AB  - Proteoglycans are an important nonfibrous matrix component of the arterial wall.
      Direct evidence for their role in resistance-sized arteries is lacking, although
      they likely have an important role in coordinating and regulating vessel
      behavior, presumably via interactions of their glycosaminoglycan chains or core
      proteins with other matrix molecules and/or the smooth muscle cell surface. The
      purpose of this study was to determine whether the removal of specific
      glycosaminoglycan chains from proteoglycans in resistance-sized mesenteric
      arteries would change the mechanical properties of the arterial wall, thereby
      affecting their functional behavior. The major finding of the study was that 65%
      removal of chondroitin-dermatan sulfate-containing glycosaminoglycans from the
      arterial wall increased vascular wall stiffness and altered the myogenic behavior
      of the artery. The significant alterations in myogenic behavior associated with
      changes in passive mechanics following partial glycosaminoglycan chain removal
      support our hypothesis that chondroitin-dermatan sulfate-containing proteoglycans
      contribute significantly to the functional behavior of resistance arteries. We
      speculate that these alterations are the result of changes in stress transfer
      between collagen fibrils and/or stress transfer between cells and collagen
      fibrils under applied pressure.

PMID- 9277516
TI  - Volume-overload cardiac hypertrophy is unaffected by ACE inhibitor treatment in
      dogs.
AB  - We tested the hypothesis that angiotensin-converting enzyme (ACE) inhibitor
      therapy prevents volume-overload hypertrophy in dogs with chronic mitral
      regurgitation (MR). Seven adult mongrel dogs receiving ramipril (R; 10 mg orally,
      twice/day) for 4 mo were compared with 11 dogs receiving no R (N) for 4 mo after
      induction of MR. Cine-magnetic resonance imaging demonstrated that left
      ventricular (LV) mass increased in the R-MR dogs [80 +/- 4 (SE) to 108 +/- 7 g, P
      < 0.01] and in the N-MR dogs (92 +/- 7 to 112 +/- 8 g, P < 0.001). LV myocyte
      cell length was greater in the R-MR and N-MR dogs (203 +/- 6 and 177 +/- 10
      microns, respectively) than in normal (144 +/- 4 microns, P < 0.05) dogs. There
      was significant loss of the collagen weave pattern by scanning electron
      microscopy in both R-MR and N-MR dogs. LV ACE and chymase activities were
      significantly elevated in R-MR and N-MR compared with normal dogs. LV angiotensin
      II (ANG II) levels in the R-MR dogs (28 +/- 12 pg/g) were reduced to levels seen
      in normal dogs (28 +/- 4 pg/g) compared with N-MR dogs (72 +/- 11 pg/g, P <
      0.05). Steady-state AT1-receptor mRNA levels decreased 66% in N-MR compared with
      normal dogs (P < 0.001) and increased 1.5-fold in R-MR compared with normal dogs
      (P < 0.01). Thus upregulation of the AT1 receptor in the R-MR hearts may provide
      a mechanism by which normal intracardiac ANG II levels could continue to mediate
      LV hypertrophy. However, the mechanism of dissolution collagen weave in both N-MR
      and R-MR hearts may be related to the stretch of volume overload.

PMID- 9277518
TI  - Stimulated neutrophils induce myosin light chain phosphorylation and isometric
      tension in endothelial cells.
AB  - The mechanism or mechanisms by which polymorphonuclear leukocytes (PMN) penetrate
      junctions between neighboring endothelial cells (EC) to traverse endothelial
      barriers remain unresolved. We report that chemoattractant-stimulated PMN induce
      a coordinate increase in both phosphorylation of serine 19 and threonine 18 of EC
      myosin regulatory light chains and isometric tension generation by EC monolayers.
      Unstimulated PMN had no effect on either parameter. These findings, coupled with
      our previous report (Huang et al., J. Cell Biol. 120: 1371-1380, 1993) that
      chemoattractant-stimulated PMN cause a rise in EC cytosolic free Ca2+, provide
      strong presumptive evidence that myosin light chain kinase is the EC enzyme
      responsible for initiating myosin light chain phosphorylation, EC contraction,
      and isometric tension generation in response to chemoattractant-stimulated PMN.
      We suggest that, by inducing phosphorylation of EC cytoskeletal proteins,
      chemoattractant-stimulated PMN induce EC to open their intercellular junctions,
      thereby facilitating transendothelial movement of these leukocytes.

PMID- 9277517
TI  - Adenylyl cyclase isoforms and vasopressin enhancement of agonist-stimulated cAMP
      in vascular smooth muscle cells.
AB  - The influence of arginine vasopressin (AVP) on agonist-stimulated adenosine 3',5'
      cyclic monophosphate (cAMP) accumulation was investigated in vascular smooth
      muscle cells (VSMC) cultured from rat thoracic aorta. Incubation of VSMC with AVP
      for 60 s produced a 2- to 2.5-fold enhancement of isoproterenol-induced cAMP
      formation. AVP also increased cAMP stimulation by the prostaglandin I2 analogue
      iloprost. The effect of AVP to enhance agonist-stimulated cAMP formation was
      completely inhibited in cells pretreated with a selective antagonist of V1
      vasopressin receptors but was not affected by blockade of V2 receptors.
      Inhibition of protein kinase C activation failed to alter the action of AVP to
      potentiate cAMP stimulation, but treatment of cells with calmodulin antagonists
      significantly attenuated this effect of the peptide. Moreover, depletion of Ca2+
      stores with thapsigargin decreased AVP enhancement of isoproterenol-stimulated
      cAMP by > 70%. The action of AVP to increase cAMP stimulation was also
      demonstrated in freshly isolated strips of rat aorta where treatment with peptide
      produced a twofold increase in isoproterenol-stimulated cAMP formation. RNA blot
      analysis indicated expression in VSMC of mRNA encoding type III adenylyl cyclase,
      a Ca(2+)-calmodulin-sensitive isoform of the effector. Furthermore, when
      detergent-solubilized membrane extract was subjected to calmodulin affinity
      chromatography, a peak of adenylyl cyclase activity was identified which had
      affinity for calmodulin matrix in the presence of Ca2+. The results indicate that
      AVP activates V1 receptors in VSMC to enhance agonist-stimulated cAMP formation
      by a Ca(2+)-calmodulin-dependent mechanism and suggest that type III adenylyl
      cyclase may provide a focal point in the VSMC for cross talk between constrictor
      and dilator pathways.

PMID- 9277519
TI  - Role of leukocyte plugging and edema in skeletal muscle ischemia-reperfusion
      injury.
AB  - The purpose of this study was to examine the relationship of increased capillary
      network resistance due to leukocyte-capillary plugging and tissue edema through
      macromolecular leakage to tissue injury after ischemia-reperfusion (I/R). After a
      3-h complete ischemia in the dorsal skinfold chamber of the awake Syrian hamster,
      the following parameters were measured: vessel diameter, macromolecular leakage,
      erythrocyte velocity, adherent leukocytes, rolling leukocytes, freely flowing
      leukocytes, functional capillary density (FCD), propidium iodide (PI)-positive
      cell nuclei, and increase in network flow resistance due to leukocyte-capillary
      plugging. These measurements were made under baseline conditions and after 0.5
      and 2 h of reperfusion for I/R alone, I/R with phalloidin (PL) treatment (to
      block leakage), and I/R with both PL and cytochalasin D (CD) (to block both
      leakage and plugging). Neither treatment had an effect on the leukocyte adherence
      or rolling. PL treatment preserved the endothelial barrier, improved FCD, and
      reduced the amount of PI measured tissue damage. CD treatment eliminated the
      increase in network resistance due to leukocyte plugging but did not improve FCD
      or tissue damage. Thus, in this I/R model, macromolecular leakage plays a role in
      tissue injury, whereas leukocyte plugging does not appear to be an important
      mechanism.

PMID- 9277520
TI  - Protein osmotic pressure gradients and microvascular reflection coefficients.
AB  - Microvascular membranes are heteroporous, so the mean osmotic reflection
      coefficient for a microvascular membrane (sigma d) is a function of the
      reflection coefficient for each pore. Investigators have derived equations for
      sigma d based on the assumption that the protein osmotic pressure gradient across
      the membrane (delta II) does not vary from pore to pore. However, for most
      microvascular membranes, delta II probably does vary from pore to pore. In this
      study, we derived a new equation for sigma d. According to our equation, pore-to
      pore differences in delta II increase the effect of small pores and decrease the
      effect of large pores on the overall membrane osmotic reflection coefficient.
      Thus sigma d for a heteroporous membrane may be much higher than previously
      derived equations indicate. Furthermore, pore-to-pore delta II differences
      increase the effect of plasma protein osmotic pressure to oppose microvascular
      fluid filtration.

PMID- 9277521
TI  - Compression of intramyocardial arterioles during cardiac contraction is
      attenuated by accompanying venules.
AB  - It was calculated how cardiac contraction influences the luminal cross-sectional
      area of a maximally dilated coronary arteriole (37-micron inner diameter at a
      pressure of 35 mmHg) that is accompanied by two equal venules (45-micron inner
      diameter at a pressure of 17 mmHg), forming a so-called "triad." It was found
      that, during a contraction with 14% cardiac muscle shortening, arteriolar area is
      virtually unaffected (increase of 4%) at the expense of a large (55%) decrease in
      venular area. For comparison, the areas of an unaccompanied arteriole and an
      unaccompanied venule were calculated to be reduced by 45 and 36%, respectively,
      demonstrating the "protective effect" on accompanied arterioles in a triad.
      During contraction, the overall resistance of a system consisting of one
      arteriole in series with two parallel venules of equal length was calculated to
      increase about twice as much for nonaccompanied vessels (resistance increases by
      a factor of 2.8) than for vessels in a triad arrangement (resistance increased by
      a factor of 1.4). The calculations show that the extravascular (intramyocardial)
      pressure, which determines vascular area, is not an independent variable as in
      the intramyocardial pump and waterfall models but depends on the vascular
      "loading" conditions. Thus the small venular pressure together with the large
      venular compliance causes the extravascular pressure to remain low during
      contraction, thereby protecting the stiff arteriole at high pressure. We conclude
      that the triad arrangement of intramyocardial coronary vessels attenuates the
      increase in coronary resistance during cardiac contraction and thus has an
      important functional advantage.

PMID- 9277522
TI  - Estimation of cardiorespiratory transfer under spontaneous breathing conditions:
      a theoretical study.
AB  - Using simulated noisy sequences of respiration and heart rate, we assessed the
      accuracy of the respiratory sinus arrhythmia transfer function (RSATF) estimation
      under three kinds of spontaneous breathing patterns: regular or tidal breathing,
      periodic breathing with apnea, and broadband breathing. Estimation employing the
      cross-power and autopower spectra of the simulated data produced RSATF estimates
      that were generally more variable than those computed with an autoregressive
      modeling approach. Variability and bias errors in the RSATF estimates became
      larger as respiratory bandwidth decreased when the breathing pattern changed from
      broadband to periodic to regular breathing. However, between frequencies of 0.1
      and 0.3 Hz, these errors fell within 12% in all breathing patterns. Error in the
      RSATF estimates was only slightly increased, with reductions in data length to as
      low as 90 s. The results suggest the feasibility of obtaining accurate estimates
      of RSATF between 0.1 and 0.8 Hz from a wide variety of conditions, such as in
      different sleep-wake states where voluntary control of breathing is not possible
      and the ventilatory pattern may vary substantially.

PMID- 9277523
TI  - Closed-loop identification of carotid sinus baroreflex open-loop transfer
      characteristics in rabbits.
AB  - In the circulatory system, a change in blood pressure operates through the
      baroreflex to alter sympathetic efferent nerve activity, which in turn affects
      blood pressure. Existence of this closed feedback loop makes it difficult to
      identify the baroreflex open-loop transfer characteristics by means of
      conventional frequency domain approaches. Although several investigators have
      demonstrated the advantages of the time domain approach using parametric models
      such as the autoregressive moving average model, specification of the model
      structure critically affects their results. Thus we investigated the
      applicability of a nonparametric closed-loop identification technique to the
      carotid sinus baroreflex system by using an exogenous perturbation according to a
      binary white-noise sequence. To validate the identification method, we compared
      the transfer functions estimated by the closed-loop identification with those
      estimated by open-loop identification. The transfer functions determined by the
      two identification methods did not differ statistically in their fitted
      parameters. We conclude that exogenous perturbation to the baroreflex system
      enables us to estimate the open-loop baroreflex transfer characteristics under
      closed-loop conditions.

PMID- 9277524
TI  - Estimation of nonmechanical VO2 in isolated rabbit heart: comparison of
      mechanical unloading and BDM method.
AB  - To understand the mechaneoenergetics of heart muscle, it is important to be able
      to accurately partition energy consumption into its two major components, that
      used for nonmechanical activity [mainly excitation-contraction (E-C) coupling and
      basal metabolism] and that used for mechanical activity (cross-bridge cycling).
      In most experiments in the beating heart, this has been accomplished by assuming
      that the unloaded oxygen consumption (VO2) represents nonmechanical VO2 and
      subtracting it from total VO2 to yield mechanical VO2. However, unloaded VO2 is
      "contaminated" by an uncertain amount of energy consumption for cross-bridge
      cycling under unloaded conditions. We recently, reported an alternative method to
      estimate nonmechanical VO2 using the negative inotropic drug 2,3-butanedione
      monoxime (BDM), which, in theory, should not include cross-bridge cycling-related
      energy consumption. In the present study, we compared changes in unloaded VO2 and
      the BDM estimate of nonmechanical VO2 as E-C coupling was varied by changing the
      perfusate Ca2+ concentration ([Ca2+]) in the isolated rabbit heart. An isolated,
      red blood cell-perfused, isovolumically contracting balloon in left ventricle
      preparation was employed. In one group (n = 8), contractility (maximal
      elastance), unloaded VO2, and the BDM estimate of nonmechanical VO2 were assessed
      at a perfusate [Ca2+] of 2.5 mM and then at 5.0 mM. In a second group (n = 6),
      perfusate was 1.0 and 2.5 mM. The change in contractility in each group as [Ca2+]
      was increased was comparable. Unloaded VO2 was systematically greater than the
      BDM estimate of nonmechanical VO2 under all conditions. However, the absolute
      change in both estimates was similar in both groups. In conclusion, over the
      range of perfusate [Ca2+] employed in this study, changes in unloaded VO2 and the
      BDM estimate of nonmechanical VO2 are similar. These results support the use of
      unloaded VO2, which is easier to measure and has less estimation error in
      individual cases than the BDM-derived value for nonmechanical VO2, as an accurate
      index of change in E-C coupling energy consumption.

PMID- 9277525
TI  - Evidence of functional beta-adrenoceptors in the cutaneous vasculature.
AB  - During a hyperthermic challenge, skin blood flow (SkBF) increases primarily
      through activation of the cutaneous active vasodilator system. However,
      mechanisms through which activation of this system elevates SkBF remain unknown.
      In this project, we sought to identify whether functional beta-adrenoceptors
      exist on cutaneous vessels and, if present, whether these receptors play an
      important role in elevating SkBF during a hyperthermic challenge. In protocol 1,
      SkBF was assessed over two intradermal microdialysis probes. Initially, both
      probes were perfused with lactated Ringer solution. Probe A was then perfused
      with a 200 microM solution of the beta-adrenoceptor agonist isoproterenol while
      probe B was perfused with a 1.7 mM solution of the beta-adrenoceptor antagonist
      propranolol. Isoproterenol perfusion significantly increased SkBF from 17.7 +/-
      2.4 to 70.8 +/- 13.2 perfusion units (PU; P < 0.05), whereas propranolol
      perfusion did not significantly affect SkBF (23.4 +/- 6.5 to 27.0 +/- 6.8 PU; P >
      0.05). After this period, the solutions perfusing the probes were switched.
      Isoproterenol did not significantly change SkBF at the propranolol-treated site
      (27.0 +/- 6.8 to 26.4 +/- 7.5 PU; P < 0.05). In protocol 2, SkBF was assessed
      over two microdialysis probes during indirect whole body heating. One probe was
      perfused with Ringer solution while the other probe was perfused with 1.7 mM
      propranolol. The degree of elevation in SkBF during heat stress at the
      propranolol-treated site (10.4 +/- 1.5 to 35.8 +/- 3.1 PU) was similar to the
      elevation in SkBF at the Ringer solution site (11.6 +/- 1.0 to 35.0 +/- 1.2 PU).
      These data demonstrate the presence of functional beta-adrenoceptors in the skin;
      however, these receptors play no significant role in mediating cutaneous
      vasodilation during indirect whole body heating.

PMID- 9277526
TI  - Beta 2-adrenergic receptors enhance contractility by stimulating HCO3(-)
      dependent intracellular alkalinization.
AB  - Previous studies established that beta 2-adrenergic receptors enhance the
      amplitude, without abbreviating the kinetics, of the twitch in adult rat
      ventricular myocytes. The present study was designed to identify the dominant
      signaling mechanism mediating this response. Myocytes from adult rat ventricles
      were loaded with the pH-sensitive fluorophore 2',7'-bis(carboxyethyl)-5(6')
      carboxyfluorescein, and simultaneous measurements of intracellular pH and
      contraction were performed during electrical field stimulation under basal
      conditions and after stimulation with isoproterenol or the selective beta 2
      receptor agonist zinterol. Inhibition of protein kinase A with H-7 completely
      inhibited the isoproterenol-dependent, but not the zinterol-dependent, positive
      inotropic response. The effect of zinterol to increase twitch amplitude was
      associated with an alkalinization of 0.07 +/- 0.02 pH unit, which was not
      prevented by inhibition of the Na+/H+ exchanger with hexamethylene-amiloride.
      Rather, removal of bicarbonate from the extracellular buffer prevented the beta 2
      receptor-dependent alkalinization as well as the positive inotropic response.
      These results indicate that beta 2-adrenergic receptors induce a positive
      inotropic response in adult rat ventricular myocytes via a adenosine 3',5'-cyclic
      monophosphate-independent mechanism that involves intracellular alkalinization
      due to activation of a bicarbonate-dependent intracellular pH regulatory
      mechanism.

PMID- 9277527
TI  - Ontogeny of the arterial and cardiopulmonary baroreflex during fetal and
      postnatal life.
AB  - The autonomic nervous system is intimately involved in regulating cardiovascular
      function. Sensing mechanisms dispersed throughout the circulation, including
      arterial baroreceptors, low pressure receptors, and chemosensitive receptors,
      continually evoke reflexes designed to maintain cardiovascular homeostasis.
      Although there is a growing body of knowledge regarding neural regulation of the
      adult cardiovascular system, characterization and understanding of these
      physiological systems during development is limited. This review highlights
      developmental changes in the arterial and cardiopulmonary baroreflex during fetal
      and postnatal life and contrasts the function of these responses with those seen
      in the adult. Baroreceptors are functional in the immature animal and reset
      toward higher pressure levels with maturation. In our ovine model, the
      sensitivity of the efferent limb of the baroreflex is greatest during fetal life
      and decreases with postnatal development. As in the adult, angiotensin II and
      arginine vasopressin interact with the sympathetic nervous system early during
      development to alter baroreflex control of the cardiovascular system. However,
      the extent to which these hormonal systems influence autonomic reflexes during
      the fetal and newborn period appears vastly different than in the adult.
      Endogenous angiotensin II significantly contributes to resetting of the arterial
      baroreflex early in life, whereas even high circulating levels of vasopressin
      have little effect on baroreflex function until adulthood. Finally, the ability
      of cardiopulmonary mechanoreceptors to regulate cardiovascular function is
      impaired early in development, in sharp contrast to the heightened sensitivity of
      the arterial baroreflex at this stage of maturation. The potential importance of
      these autonomic reflexes on cardiovascular function during the perinatal period
      is highlighted.

PMID- 9277528
TI  - Development of diurnal organization of EEG slow-wave activity and slow-wave sleep
      in the rat.
AB  - This study characterizes the development of diurnal patterns of slow-wave sleep
      (SWS) distribution and SWS electroencephalographic (EEG) delta-power (DP) density
      in 12- to 24-day-old rats (P12-P24). Diurnal organization in sleep-wake
      distribution was established by P20. A decline in SWS DP across the light phase
      did not appear until P24. Before P20, SWS DP increased across the light phase in
      a pattern inverse to that typically seen in adult rats. At P20, SWS DP was evenly
      distributed across the light phase, and at P24, SWS DP declined across the light
      phase. The transient dissociation between diurnal organization in sleep-wake
      cycles and SWS DP suggests that circadian and homeostatic sleep regulatory
      mechanisms develop at different rates in the postnatal period.

PMID- 9277529
TI  - Reward comparison in chronic decerebrate rats.
AB  - The simultaneous contrast paradigm was used to evaluate responsiveness to a low
      (0.05 M) and a high (0.5 M) concentration of sucrose under two conditions in
      intact and chronic decerebrate rats. In one condition the low concentration was
      presented on one day and the high concentration on another. In the other
      condition presentation of the two concentration was alternated within the same
      daily session. In each case there was a total of 40 trials/day during which the
      stimulus was delivered intraorally for 2 s at a rate of 1.5 ml/min with a 30-s
      intertrial interval. The results showed that the intact rats always licked more
      for the high than for the low concentration of sucrose but that the magnitude of
      the effect was larger when given the opportunity to compare the two
      concentrations within the same daily session. The decerebrate rats produced a
      similar pattern, but the concentration effect was evident only when the stimuli
      were alternated within the same daily session. These data stand as the first
      evidence that the isolated caudal brain stem is adequate for the expression of a
      behavior that depends on comparison processes involving short-term memory.

PMID- 9277530
TI  - Tonic glutamate-mediated control of rostral ventrolateral medulla and sympathetic
      vasomotor tone.
AB  - Sympathoexcitatory neurons in the rostral ventrolateral medulla (RVLM) play a key
      role in the tonic maintenance of resting arterial pressure. Removal of tonically
      active inhibitory inputs to the RVLM provided by the caudal ventrolateral medulla
      (CVLM) elicits a large increase in arterial pressure. The present study addresses
      the hypothesis that excitatory amino acids (EAA) provide the excitation of the
      RVLM responsible for the increase in arterial pressure that occurs after
      withdrawal of CVLM-mediated inhibition of the RVLM. In rats anesthetized with
      either alpha-chloralose or urethan, inhibition of the CVLM by local injection of
      muscimol markedly elevated arterial pressure. Subsequent injection of the EAA
      receptor antagonist kynurenic acid into the RVLM caused arterial pressure to fall
      to levels comparable to those that occur-with total autonomic blockade. In
      contrast, injection of kynurenic acid into the RVLM of control rats had little
      effect on arterial pressure. These results indicate that the large increase in
      arterial pressure produced by inhibition of the CVLM is mediated by EAA
      excitation of RVLM neurons. Furthermore, these data suggest that EAA play a
      prominent role in the tonic excitation of RVLM neurons, but, in intact rats,
      inhibition of EAA in the RVLM elicits no change in arterial pressure because of
      removal of inhibitory as well as excitatory drives of the RVLM.

PMID- 9277531
TI  - Effect of autonomic blockade on power spectrum of heart rate variability during
      exercise.
AB  - To validate power spectral analysis of heart rate variability (HRV) as an
      autonomic indicator during exercise, ten males performed four identical
      progressive cycling tests during infusions of saline, esmolol (beta 1-blocker),
      glycopyrrolate (muscarinic blocker), or both drugs. Power spectra were
      constructed from the recorded electrocardiogram by Fourier algorithm and
      integrated for low-frequency power (LF) and high-frequency power (HF). Four
      different LF bands (0.004-0.1, 0.004-0.15, 0.05-0.1, and 0.05-0.15 Hz) and two
      different HF bands (0.1-1.0 and 0.15-1.0 Hz) were evaluated. The parasympathetic
      index, HF, decreased exponentially with workload and was attenuated by
      glycopyrrolate and combined treatments with both HF frequency bands measured.
      Whereas some sympathetic indexes (LF/total power and LF/HF) did reflect expected
      increases in sympathetic nerve activity associated with progressive increases in
      work intensity, none of the measured increases responded appropriately to
      autonomic blockade. It is concluded that HRV is a valid technique for noninvasive
      measurement of parasympathetic tone during exercise, but its validity as a
      measure of sympathetic tone during exercise is equivocal.

PMID- 9277532
TI  - Regulation of angiotensin II AT1 and AT2 receptors in neonatal ureteral
      obstruction.
AB  - Chronic unilateral ureteral obstruction (UUO) in early development activates the
      intrarenal renin-angiotensin system and leads to profound renal vasoconstriction,
      renal growth arrest, and interstitial fibrosis. To investigate the response of
      the AT1 and AT2 subtypes of the angiotensin II (ANG II) receptors to UUO, Sprague
      Dawley rats underwent UUO or control sham operation in the first 48 h of life and
      were studied 1-28 days later. Renal mRNA for renin, AT1 and AT2 receptor, and
      receptor binding and distribution were determined. In contrast to controls, renin
      mRNA increased from 14 to 28 days in the obstructed kidney. After ipsilateral
      UUO, AT1 mRNA was suppressed at 1 day, but had increased compared with controls
      at 28 days. AT2 receptor mRNA fell rapidly in all kidneys from 1 to 3 days of
      age, after which it remained undetectable. Compared with the intact opposite
      kidney, AT2 mRNA was suppressed in the obstructed kidney 1 day after UUO.
      Compared with controls, AT1 and AT2 receptor binding was decreased by ipsilateral
      UUO at 1 day, whereas AT1 binding was increased at 28 days. Renal ANG II content
      was increased in the obstructed compared with the intact opposite kidney 28 days
      after UUO. In view of the increase in renal renin and angiotensin II production
      resulting from UUO, increased renal AT1 mRNA and receptor binding are likely to
      contribute to the vasoconstriction and interstitial fibrosis of the neonatal
      kidney after prolonged UUO.

PMID- 9277533
TI  - Effect of angiotensin II receptor blockade on proximal tubular fluid
      reabsorption.
AB  - The effect of physiological concentrations of angiotensin II on proximal tubular
      fluid reabsorption remains controversial. To investigate the effect of blockade
      of intratubular AT1 receptors on tubular reabsorption, losartan (10(-5) M) was
      administered by microperfusion into an early proximal convolution of halothane
      anesthetized Sprague-Dawley rats. Four parameters that depend on the rate of
      proximal fluid reabsorption were measured: proximal intratubular pressure
      (Pprox), early and late proximal flow rate, and early distal NaCl concentration.
      Pprox decreased by 0.5 +/- 0.1 mmHg, late proximal flow rate decreased by 2.0 +/-
      0.8 nl/min, and early distal NaCl concentration decreased by 4.3 +/- 0.8 mM (mean
      +/- SE). No changes were observed after microperfusion with saline. Because the
      tubuloglomerular feedback mechanism was operating in the closed-loop mode, the
      decreased NaCl load to the macula densa will be compensated by an increase in the
      single-nephron glomerular filtration rate. In agreement with this, the early
      proximal flow rate, measured proximal to the site of losartan administration,
      increased by 5.7 +/- 1.3 nl/min. The increase in the rate of proximal
      reabsorption between the early and late proximal convolutions was estimated to be
      7.8 nl/min (approximately 36%). It is concluded that a decrease in local luminal
      angiotensin II levels and/or AT1 receptor activity under free flow conditions
      increases the rate of proximal tubular fluid reabsorption.

PMID- 9277534
TI  - Hyperplasia and hypertrophy of chicken cardiac myocytes during posthatching
      development.
AB  - For characterization of the growth pattern of cardiac myocytes during
      posthatching development, cardiac myocytes were enzymatically isolated from the
      ventricles of 1-, 15-, 29-, and 42-day-old chickens for measurement of myocyte
      nucleation, length, width, volume, and number, and for immunolabeling of
      cytoskeletal proteins. Ventricular myocyte number increased 156% from day 1 to
      day 42. Average cell volume increased more than 400%, and myocytes lengthened
      125%, but cell width only increased 53% during this period. All myocytes were
      mononucleated at day 1. At day 15, 18% of myocytes became binucleated with < 1%
      of myocytes containing more than two nuclei. Interestingly, binucleated myocytes
      were able to divide with two nuclei going through mitosis at the same time. As
      demonstrated by staining with tubulin and alpha-actinin antibodies, two mitotic
      spindles and two cleavage furrows were formed in dividing binucleated myocytes.
      At day 42, binucleated myocytes increased to 44% with 11% of myocytes containing
      more than two nuclei. Sarcomeric alpha-actinin was partially disassembled in
      prometaphase and was reorganized into regular Z lines of sarcomeres in telophase.
      Desmin was disassembled in prophase and was reassembled during late telophase.
      These results suggest that chicken myocytes undergo hypertrophy and continue to
      proliferate during posthatching maturation, although it is currently believed
      that myocytes of all vertebrates withdraw from the cell cycle shortly after
      birth. We provide direct evidence for the first time of in vivo myocyte division
      in 6-wk-old chicken hearts.

PMID- 9277535
TI  - Effects of natriuretic peptides and nitroprusside on venous function in trout.
AB  - Active venous regulation of cardiovascular function is well known in mammals but
      has not been demonstrated in fish. In the present studies, the natriuretic
      peptides (NP) rat atrial natriuretic peptide (ANP) and trout ventricular
      natriuretic peptide (VNP), clearance receptor inhibitor SC-46542, and sodium
      nitroprusside (SNP) were infused into unanesthetized trout fitted with pressure
      cannulas in the ventral aorta, dorsal aorta, and ductus Cuvier, and a ventral
      aorta (VA) flow probe was used to measure cardiac output (CO). In another group,
      in vivo vascular (venous) capacitance curves were obtained during ANP or SNP
      infusion. The in vitro effects of NP on vessels and the heart were also examined.
      ANP, VNP, and SC-46542 decreased central venous pressure (PVen), CO, stroke
      volume (SV), and gill resistance (RG), whereas systemic resistance (RS) and heart
      rate (HR) increased. Dorsal aortic pressure (PDA) transiently increased and then
      fell even though RS remained elevated. ANP decreased mean circulatory filling
      pressure (MCFP), increased vascular compliance at all blood volumes, and
      increased unstressed volume in hypovolemic fish. ANP had no direct effect on the
      heart. ANP responses in vivo were not altered in trout made hypotensive by prior
      treatment with the angiotensin-converting enzyme inhibitor lisinopril. SNP
      reduced ventral aortic pressure (PVA), PDA, and RS, increased CO and HR, but did
      not affect PVen, SV, or RG. SNP slightly decreased MCFP but did not affect
      compliance or unstressed volume. In vitro, large systemic arteries were more
      responsive than veins to NP, whereas SNP relaxed both. These results show that,
      in vivo, NP decrease venous compliance, thereby decreasing venous return, CO, and
      arterial pressure. Conversely, SNP hypotension is due to decreased RS. This is
      the first evidence for active regulation of venous capacitance in fish, which
      probably occurs in small veins or venules. The presence of venous baroreceptors
      is also suggested.

PMID- 9277536
TI  - Linear and nonlinear properties of heart rate control in infants at risk.
AB  - The aim of this study was to test whether the heart rate (HR) control in infants
      at risk differs in comparison with healthy infants. Twelve former preterm infants
      suffering from bronchopulmonary dysplasia and 18 control infants, matched for
      their postconceptional age, were examined polygraphically during quiet and active
      sleep. HR, low-frequency (LF) power, high-frequency (HF) power, total power, and
      the ratio of LF to HF power (LF/HF) of the instantaneous HR spectra were
      calculated for linear analysis. The largest Lyapunov exponent (LLE) of the R-R
      interval time series was calculated to determine a nonlinear property of HR.
      Infants at risk had significantly lower LF power (median: 0.51 x 10(-3) vs. 1.16
      x 10(-3) Hz2) and lower LF/HF (median: 1.05 vs. 1.94) during quiet sleep. LLE was
      positive, revealing low-dimensional chaotic behavior of HR control, and did not
      differ between both groups (median: quiet sleep, 0.05 bit/s vs. 0.06 bit/s;
      active sleep, 0.16 bit/s vs. 0.15 bit/s). Sleep state-related changes in spectral
      parameters and LLE were similar in both groups. In infants at risk, the lower
      LF/HF during quiet sleep can be interpreted in terms of changes in the rhythmic
      components of the sympathovagal balance of the autonomic system, which is an
      expression of linear properties of HR control. Conversely, the lack of
      differences in LLE between both groups indicates similar nonlinear properties of
      the control system.

PMID- 9277537
TI  - Systemic immune changes following meal intake in humans.
AB  - Food intake represents a high intestinal antigen exposition requiring host
      defense. Besides local immune activation, this defense includes a coordinate
      systemic immune response, which may serve to support local immunity. This study
      examined influences of a standardized high-protein meal on peripheral blood
      mononuclear cell counts; on the in vitro mitogen-stimulated production of tumor
      necrosis factor-alpha, interleukin-1 beta, interleukin-6, and interferon-gamma;
      on the in vivo plasma levels of tumor necrosis factor-alpha and interleukin-6;
      and on plasma concentrations of cortisol and growth hormone. Ten healthy men (18
      35 yr) participated in two experimental sessions in a balanced order. On one
      occasion, subjects fasted; on the other, they received a high-protein meal at
      1230. Blood was sampled every 15 min. Whereas the numbers of neutrophils and
      platelets were increased for more than 2.5 h after meal intake (P < 0.01)
      lymphocyte counts decreased (P < 0.01). Meal intake also decreased the production
      of interferon-gamma but did not affect the production and plasma levels of the
      other cytokines. Changes in immune cell distribution and function were
      accompanied by a strong postprandial rise in plasma cortisol concentrations. Some
      of the systemic immune changes, like the emigration of lymphocytes, probably into
      extravascular abdominal tissues, may serve to support local immune defense.

PMID- 9277538
TI  - L-threonine injection into PPC modifies food intake, lateral hypothalamic
      activity, and sympathetic discharge.
AB  - Food intake and the firing rate of lateral hypothalamic neurons and nerves
      innervating interscapular brown adipose tissue (IBAT), along with IBAT and
      colonic temperatures, were monitored in male Sprague-Dawley rats fed a threonine
      free diet. These variables were measured before and after a bilateral injection
      of L-threonine (2 nmol into each side) into the prepiriform cortex (PPC). The
      same variables were also monitored in 1) rats fed a threonine-free diet and
      injected with saline, 2) animals fed a standard diet and injected with L
      threonine, and 3) rats fed a standard diet and injected with saline. The results
      showed that injection of L-threonine into PPC increases food intake and firing
      rate of lateral hypothalamic neurons, whereas it decreases the sympathetic
      discharge and body temperature in animals fed a threonine-free diet. No changes
      were found in the animals fed a standard diet. These findings suggest a
      correlation between 1) threonine level in the PPC and 2) lateral hypothalamic
      activity and sympathetic discharge to IBAT.

PMID- 9277539
TI  - Baroreceptor-independent renal nerve inhibition by intracerebroventricular
      angiotensin II in conscious sheep.
AB  - The effect of central administration of angiotensin II (ANG II) on efferent renal
      sympathetic nerve activity (RSNA) was studied in conscious sheep. ANG II (1
      nmol/h), infused for 30 min into the lateral cerebral ventricles in five sheep,
      did not alter mean arterial pressure (MAP) but reduced RSNA to 38 +/- 5% of
      control. Intracerebroventricular infusion of higher doses of ANG II (3 and 10
      nmol/h), which increased MAP by 12 +/- 2 and 14 +/- 3 mmHg, respectively, reduced
      RSNA to 9 +/- 5 and 11 +/- 7% of control. MAP and RSNA gradually returned to
      control over a period of 2 h after the infusions. Intracerebroventricular
      losartan (1 mg/h for 1 h before, and then during, angiotensin infusion) blocked
      all the effects of angiotensin (3 nmol/h). Baroreflex relationships constructed
      from the beat-to-beat relationship of RSNA to diastolic pressure showed a
      significant leftward shift during intracerebroventricular ANG II compared with
      the control relationship. The beat-to-beat relationship between central venous
      pressure and RSNA was abolished during intracerebroventricular infusion of ANG
      II. These findings demonstrate that intracerebroventricular ANG II has a direct
      central inhibitory action on RSNA that is independent of both arterial and low
      pressure baroreceptors. This effect of angiotensin is mediated by central
      angiotensin AT-1 receptors.

PMID- 9277541
TI  - Age-related changes in the pressure diuresis and natriuresis response.
AB  - The renal-excretory responses to changes in renal perfusion pressure (RPP) were
      studied in anesthetized young (3 mo old), adult (12 mo old), and senescent (24 mo
      old) rats to evaluate whether the pressure diuresis and natriuresis mechanism is
      altered as a function of age. Experiments were performed in anesthetized animals
      in which nervous and systemic hormonal influences to the kidney were fixed. Mean
      arterial pressure was similar in all three groups: 97.6 +/- 2.6, 102.1 +/- 3.7,
      and 95.2 +/- 5.2 mmHg in young, adult, and senescent rats, respectively. The
      relationships between RPP and diuresis/natriuresis or fractional excretions of
      water and sodium were similar in young and adult rats. However, in senescent rats
      the pressure-diuretic and pressure-natriuretic responses were slightly shifted to
      the right, so that diuresis and natriuresis were significantly lower at higher
      levels of RPP. Glomerular filtration rate was well autoregulated, and there were
      no differences between young and adult rats at each level of RPP. However, a
      significantly lower glomerular filtration rate was observed in senescent rats.
      These results indicate an age-related decline in the pressure-dependent sodium
      and water excretion that appears to be due to a decrease in glomerular filtration
      and an increase in tubular sodium reabsorption.

PMID- 9277540
TI  - Functional and structural changes in the thick ascending limb of Henle's loop in
      rats with liver cirrhosis.
AB  - Five weeks after common bile duct ligation (CBL), Wistar rats had histologically
      verified liver cirrhosis with sodium retention but without ascites. Plasma
      concentrations of vasopressin and aldosterone were normal. Glomerular filtration
      rate was unchanged, although renal plasma flow was increased. A test dose of
      furosemide (7.5 mg/kg body wt iv) produced significantly greater diuretic (+59%)
      and natriuretic (+66%) responses in Wistar CBL rats than in sham-operated
      controls. Stereological examination of kidneys demonstrated a 47% increase in the
      volume of the inner stripe of the outer medulla, with a 55% increase in the
      volume of thick ascending limb of Henle's loop (TALH) epithelium in cirrhotic
      Wistar rats relative to controls. CBL produced a similar degree of liver
      cirrhosis in vasopressin-deficient Brattleboro rats. However, both functional and
      structural renal changes observed in cirrhotic Wistar rats were absent in
      vasopressin-deficient cirrhotic Brattleboro rats. These results suggest a
      permissive action of vasopressin for the adaptive changes in TALH in rats with
      experimental liver cirrhosis. Our results are consistent with the hypothesis that
      increased sodium chloride reabsorption in the TALH may contribute to the early
      sodium retention that precedes ascites formation in rats with secondary biliary
      liver cirrhosis.

PMID- 9277542
TI  - An ATP-sensitive potassium channel activator reduces infarct volume in focal
      cerebral ischemia in rats.
AB  - ATP-sensitive potassium channels are activated under hypoxic or ischemic
      conditions. The effects of ATP-sensitive potassium channel activators on
      cerebrovasculature and cerebral blood flow (CBF) are not well understood. We
      examined the effect of the ATP-sensitive potassium channel activator Y-26763 on
      focal cerebral ischemia in rats. In 24 spontaneously hypertensive rats, either Y
      26763 (24 micrograms/kg) or vehicle was given by intracarotid infusion over 60
      min, starting 30 min before photochemically induced thrombotic occlusion of the
      middle cerebral artery. CBF was measured by laser-Doppler flowmetry in the peri
      ischemic penumbral cortex. Although Y-26763 lowered systemic blood pressure by 13
      mmHg, the infarct volume assessed 3 days after the occlusion was significantly
      smaller in the Y-26763-treated group (n = 12, 71.2 +/- 22.0 mm3) than in the
      control group (n = 12, 94.7 +/- 20.4 mm3, P = 0.013). Y-26763 did not affect CBF
      before or after occlusion compared with CBF values of the control group. The
      results are consistent with the view that the activation of the ATP-sensitive
      potassium channel is neuroprotective in focal cerebral ischemia.

PMID- 9277543
TI  - Polyethylene glycol-induced calcium appetite.
AB  - Polyethylene glycol (PEG) has been used to investigate the physiological basis of
      sodium intake because it sequesters sodium from the extracellular fluid (ECF) and
      causes rats to drink concentrated NaCl solutions. To test the hypothesis that PEG
      also depletes ECF calcium and thus activates calcium intake, male Sprague-Dawley
      rats received two-bottle tests with a choice between a taste solution and water.
      Relative to intakes after control injections, rats injected with PEG (5 ml of 30%
      wt/wt sc) drank significantly greater volumes of several calcium solutions (0.1,
      1, 10, or 32 mM CaCl2 or 10 or 100 mM calcium lactate). They also drank more 10
      mM SrCl2, 300 mM NaCl, and 100 mM KHCO3, drank less 10 mM sodium saccharin, and
      did not alter intakes of 10 or 100 mM KCl, 32 mM NH4Cl, 10 mM AlCl3, 10 mM FeCl2,
      100 mM CaCl2, or 1,000 mM NaCl. Thus PEG treatment produced an appetite that was
      specific to low and moderate concentrations of calcium, sodium, and perhaps
      bicarbonate. The physiological basis for this appetite was explored. At 24 h
      after PEG injection, plasma total calcium concentrations were either unaltered or
      increased, but plasma ionized calcium concentrations were reduced. Concentrations
      of parathyroid hormone and calcitonin but not 1 alpha, 25-dihydroxyvitamin D3
      were elevated. Perhaps one or more of these changes in calcium homeostasis is
      responsible for the increased calcium intake. Whatever the mechanism, it is clear
      that PEG treatment induces an appetite for calcium in addition to the well-known
      appetite for sodium.

PMID- 9277544
TI  - Frequency-dependent modulation of renal blood flow by renal nerve activity in
      conscious rabbits.
AB  - To examine the influence of the various frequency components of renal sympathetic
      nerve activity (RSNA) on renal blood flow (RBF) dynamics, a Doppler flow probe
      and renal nerve electrode were implanted on the left renal artery of 10 rabbits.
      Experiments were performed 4-9 days after surgery. Physiological changes in RSNA
      were induced by subjecting the rabbits to periods of breathing hypoxic gas
      mixtures. Signals were sampled at 1 kHz and analyzed by spectral analysis. During
      moderate hypoxia (arterial PO2 = 44 +/- 1 mmHg), arterial pressure and heart rate
      did not change, averaged RSNA increased by 90 +/- 7%, and RBF fell by 18 +/- 3%.
      In a separate group of renal-denervated rabbits (n = 6), no changes in RBF
      occurred during hypoxia. In intact rabbits, 53 +/- 4% of spectral density power
      of RSNA was found at the cardiac frequency and the remainder was predominantly
      coupled to respiration (approximately 0.9 Hz). During moderate hypoxia the
      amplitude of the RSNA oscillations increased 17 +/- 6 times at the cardiac
      frequency and 10 +/- 3 times at the respiration-related frequency. Modulation of
      RBF variability by the fluctuations of RSNA at the cardiac- and respiration
      related frequency was, however, small. The normalized transfer gain between RSNA
      and RBF was approximately 0.1 at > 0.5 Hz. This means that, at > 0.5 Hz,
      maximally 10% of the amplitude of the RSNA oscillations is transmitted to
      corresponding RBF fluctuations. These transfer properties did not change during
      hypoxia. At < 0.5 Hz the transfer gain between RSNA and RBF increased. During
      moderate hypoxia, 0.3-Hz coherent oscillations of RSNA and RBF were found. In
      renal-denervated rabbits, 0.3-Hz oscillations in RBF were absent. Thus the renal
      vasculature was able to follow relatively low-frequency (< 0.5-Hz) fluctuations
      of RSNA and responded with corresponding oscillations in RBF. In contrast, the
      renal vasculature responded with increased constriction at the high-frequency (>
      0.5-Hz) fluctuations of RSNA. These findings suggest that, in conscious rabbits,
      high-frequency oscillations of RSNA contribute to the vasoconstrictor tone,
      whereas the lower frequencies of RSNA contribute to the variability of RBF.

PMID- 9277545
TI  - Peripheral endotoxin increases splenic sympathetic nerve activity via central
      prostaglandin synthesis.
AB  - We tested whether prostaglandin synthesis mediates the lipopolysaccharide (LPS)
      induced increase in splenic sympathetic nerve activity. Sprague-Dawley rats were
      pretreated with intravenous or intracerebroventricular injections of
      indomethacin, and splenic nerve activity was recorded after intravenous
      injections of LPS. In vehicle-pretreated rats, 100 micrograms LPS induced a 62.8
      +/- 5.6% increase in splenic nerve activity beginning 22.7 +/- 2.7 min
      postinjection. All vehicle-pretreated animals responded to high (100 micrograms,
      5 of 5 animals) and low (10 micrograms, 8 of 8 animals) doses of LPS. Both
      intravenous (15 mg/kg) and intracerebroventricular (50 micrograms) pretreatments
      with indomethacin delayed (F1.19 = 30.66, P < 0.001) the increase in nerve
      activity after 100 micrograms LPS. When given intravenously, 50 micrograms
      indomethacin (the intracerebroventricular dose) did not delay the response to
      intravenous LPS, indicating that the effects of intracerebroventricular
      indomethacin pretreatment were restricted to the central nervous system.
      Importantly, intracerebroventricular indomethacin reduced (2 of 7 animals) or
      completely blocked (5 of 7 animals) the splenic nerve response to the low dose of
      LPS (10 micrograms, iv). The indomethacin effects could not be accounted for by
      central release of vasopressin because intracerebroventricular injection of
      indomethacin did not alter baseline nerve activity or blood pressure, whereas
      intracerebroventricular injection of vasopressin rapidly increased both measures.
      Additionally, central injection of LPS did not elevate splenic nerve activity,
      whereas intracerebroventricular injection of prostaglandin E2 induced a rapid
      (2.2 +/- 2.7 min) increase in splenic nerve activity. These data indicate that
      central prostaglandin synthesis is an intermediate step whereby systemic LPS
      elicits an increase in sympathetic outflow to an immune organ.

PMID- 9277546
TI  - Effects of vestibular and oculomotor stimulation on responsiveness of the carotid
      cardiac baroreflex.
AB  - Twelve healthy men underwent measurement of their carotid-cardiac baroreflex
      response during varying conditions of vestibulo-oculomotor stimulation to test
      the hypothesis that vestibular and/or oculomotor stimulation associated with head
      movements in the yaw plane inhibit baroreflex control of heart rate. We assessed
      the carotid-cardiac baroreflex response by plotting R-R intervals (in
      milliseconds) at each of eight neck pressure steps with their respective carotid
      distending pressures (in millimeters mercury). Baroreflex sensitivity was
      measured under four experimental conditions: 1) sinusoidal whole body yaw
      rotation of the subject in the dark without visual fixation (combined vestibular
      oculomotor stimulation); 2) yaw oscillation of the subject while tracking a small
      head-fixed light moving with the subject (vestibular stimulation without eye
      movements); 3) subject stationary while fixating on a small light oscillating in
      yaw at the same frequency, peak acceleration, and velocity as the chair (eye
      movements without vestibular stimulation); and 4) subject stationary in the dark
      (no eye or head motion). Head motion alone reduced baseline baroreflex
      responsiveness by 30% from 3.8 +/- 0.5 to 2.6 +/- 0.5 ms/mmHg. Eye motion alone
      also reduced the baroreflex response by 13% (0.5 ms/mmHg) to 3.3 +/- 0.5 ms/mmHg.
      During head motion, the effect of eye motion was negligible (2.7 +/- 0.4
      ms/mmHg). These results suggest that vestibular stimulation associated with head
      movements in yaw inhibits vagally mediated baroreflex control of heart rate,
      whereas oculomotor stimulation is less of a factor and only in the absence of
      vestibular stimulation.

PMID- 9277547
TI  - Expression and secretion of lipocortin 1 in gut inflammation are not regulated by
      pituitary-adrenal axis.
AB  - Lipocortin 1 is considered a mediator of the anti-inflammatory actions of
      glucocorticoids. We have shown that this protein is overexpressed and secreted
      during an experimental colitis induced by intraluminal injection of
      trinitrobenzenesulfonic acid (TNBS) in rats. We studied here the in vivo
      regulation of lipocortin 1 expression and secretion in this model, either by
      glucocorticoids using adrenalectomized or dexamethasone-treated (3 mg/24 h)
      animals or by pituitary factors using hypophysectomized animals. Inflammation was
      evaluated by measuring myeloperoxidase activity and by histological scoring of
      the damage. Lipocortin 1 was detected by immunoblotting, and its secretion was
      studied by incubating colonic specimens in-culture medium. In the colon of TNBS
      injected animals, cumulative histological damage scores were increased in
      adrenalectomized and decreased in dexamethasone-treated animals compared with
      control and hypophysectomized animals. The colons of all TNBS-injected animals
      (controls, adrenalectomized, dexamethasone treated, hypophysectomized)
      overexpressed and secreted lipocortin 1. In conclusion, the induction of
      lipocortin 1 overexpression and secretion during this colitis occurs
      independently of glucocorticoids or pituitary factors.

PMID- 9277548
TI  - Effect of oxidative stress and acidosis on diaphragm contractile function.
AB  - Acidosis during exercise has long been associated with skeletal muscle fatigue.
      Recent evidence also has linked reactive oxygen species (ROS) with fatigue in
      skeletal muscle, including the diaphragm. We hypothesized that acidosis (designed
      to mimic blood pH during maximal exercise) would worsen ROS-induced depression of
      diaphragm contractility. The xanthine oxidase (XO) reaction in solution (0.01
      U/ml) allows direct assessment of the effects of oxidant stress by ROS. Costal
      diaphragm fiber bundles from 24 Sprague-Dawley rats (200-250 g) were divided into
      four treatment groups: 1) pH 7.4, no XO (H); 2) pH 7.4 + XO (HXO); 3) pH 7.0, no
      XO (L); and 4) pH 7.0 + XO (LXO). Baseline twitch mechanics and force-frequency
      relationships (Pre) were determined in control Krebs solution (pH 7.4, no XO)
      before treatment. Treatment solutions were introduced, and the diaphragm
      underwent 2 min of contractions at 25 Hz (250 ms) at a rate of 1/s. After 10 min
      of recovery, the control solution was reintroduced into the bath and
      postcontractile function (Post) was measured. Significant reductions in twitch
      tension and low-frequency tetanic tension were greater in HXO and LXO compared
      with H, without an effect on maximal tetanic tension. One-half relaxation time
      was prolonged only by the combination of acidosis and oxidative stress. Addition
      of superoxide dismutase (50 U/ml) worsened and catalase (1,800 U/ml) attenuated
      XO-induced depression of diaphragm contractility. We concluded that XO induced a
      reduction of low-frequency tension in the fatigued diaphragm, which was mediated
      directly or indirectly through hydrogen peroxide and was exacerbated to a modest
      extent with acidosis.

PMID- 9277549
TI  - Enhanced responsiveness of cardiac vagal chemosensitive endings to bradykinin in
      heart failure.
AB  - There is good evidence that the cardiopulmonary and arterial baroreflexes are
      blunted in chronic heart failure (HF). Other evidence, however, suggests that the
      cardiac chemoreflex is enhanced during HF. In the present study, we sought to
      determine whether HF alters the sensitivity of cardiac vagal chemosensitive
      endings to bradykinin (BK), an endogenous mediator that activates ventricular C
      fiber afferents. We measured the activity of cardiac vagal single fibers and
      compared the afferent responses to left atrial injections of BK and capsaicin in
      sham-operated and pacing-induced HF dogs. The capsaicin-sensitive endings did not
      respond to changes in cardiac pressures evoked by vascular snares and were C
      fiber endings (0.8-2.1 m/s). Most were located in the left heart. There was no
      difference in rate or pattern of resting discharge of the cardiac vagal fibers
      between HF and sham groups (1.5 +/- 0.5 vs. 1.3 +/- 0.3 impulses/s,
      respectively). The afferent response to BK (0.001-1 microgram/kg), but not
      capsaicin (1-10 micrograms/kg), was greater in HF compared with sham dogs.
      Captopril (2 mg/kg i.v.) significantly enhanced resting discharge (P < 0.05) from
      cardiac chemosensitive vagal afferents in HF but not sham dogs. The afferent
      response to BK in both groups was significantly (P < 0.05) and similarly
      enhanced. Indomethacin (5 mg/kg i.v.) significantly inhibited resting discharge
      (P < 0.05) and nearly abolished the afferent responses to lower doses of BK in
      HF, but did not affect resting discharge and less effectively attenuated
      responses to BK in sham dogs. Responses to capsaicin did not differ between HF
      and sham animals. From these results, we conclude that 1) resting discharge from
      cardiac vagal chemosensitive endings is not altered in HF, 2) these vagal endings
      exhibit an enhanced sensitivity to exogenous BK but not to capsaicin in the HF
      state, 3) angiotensin-converting enzyme activity inhibits resting discharge from
      these afferents in HF, and 4) the cyclooxygenase system contributes to the
      enhanced BK responsiveness of cardiac chemosensitive endings in HF.

PMID- 9277550
TI  - Mechanisms compensating Na and water retention induced by long-term reduction of
      renal perfusion pressure.
AB  - Endogenous downregulation of plasma aldosterone (Aldo) concentration, despite
      increased plasma renin activity (PRA), has been suggested to compensate Na and
      water retention, which is induced by long-term reduction of renal perfusion
      pressure (rRPP). To determine whether fixed plasma Aldo concentration would
      prevent equilibration of 24-h Na and water balances during rRPP, chronically
      instrumented, freely moving beagle dogs were kept under standardized conditions
      (daily intake 5.5 mmol Na/kg body wt) and studied for 4 consecutive days under
      the following conditions: control without rRPP (protocol 1) and rRPP + infusion
      of Aldo (rRPP + Aldo, protocol 2). Because Aldo administration reduces PRA and,
      thereby, angiotensin II (ANG II) levels ANG II was additionally infused in
      protocol 3 (rRPP + ANG II + Aldo). During rRPP + Aldo, 24-h Na balances were
      never equilibrated. Daily Na retention was approximately 3.5 mmol/kg body wt on
      day 1 and decreased to approximately 1.6 mmol/kg body wt on day 4; 24-h water
      balances changed in a similar manner. PRA decreased stepwise. On all rRPP + ANG
      II + Aldo days, Na and water retentions were more extensive than during rRPP +
      Aldo. Daily Na retention decreased from approximately 4.4 mmol/kg body wt on day
      1 to approximately 3.0 mmol/kg body wt on day 4. Plasma atrial natriuretic
      peptide increased during both protocols. It is concluded that 1) endogenous
      downregulation of components of the renin-angiotensin-aldosterone system is a
      pivotal compensatory mechanism to reduce Na and water retention and 2)
      natriuretic and diuretic factors seem to be of minor potency, because not even
      the sum of all could counterbalances the Na- and water-retaining effects of Aldo
      and ANG II.

PMID- 9277551
TI  - Sex differences in immunocompetence differ between two Peromyscus species.
AB  - Males generally exhibit reduced immunocompetence and greater susceptibility to
      disease than females. The explanations for why males may be more susceptible to
      disease than females fall into two categories: 1) the proximate mechanisms
      mediating immunity, such as hormonal mechanisms, and 2) variation in reproductive
      success between the sexes. The present study examined the extent to which these
      factors contribute to sex differences in cell-mediated immune function in
      polygynous Peromyscus maniculatus and monogamous Peromyscus californicus.
      Prevailing hypotheses suggest that, because variation in male and female
      reproductive success is greater among polygynous than monogamous species, sex
      differences in immunocompetence should be greater among polygynous than
      monogamous species as well. In contrast to these predictions, sex differences in
      cell-mediated immunity and body mass were only observed among monogamous P.
      californicus, in which females exhibited higher splenocyte proliferation in
      response to the T cell mitogen, concanavalin A, and weighed less than male
      conspecifics. Male P. maniculatus had higher serum testosterone concentrations
      than male P. californicus, but females of the two species did not differ in
      circulating estradiol concentrations. Sex steroid concentrations were not
      correlated with either immunocompetence or body mass; however, large P.
      californicus males exhibited reduced immune responses. Taken together, these
      results do not support the hypothesis that sex differences in immunocompetence
      are more pronounced among polygynous compared with monogamous species.
      Furthermore, these data suggest that circulating testosterone does not mediate
      sex differences in immuno-competence or body mass in P. californicus.

PMID- 9277552
TI  - Nitric oxide-synthesizing perivascular nerves in the rat middle cerebral artery.
AB  - Although perivascular nerves containing nitric oxide synthase (NOS) have been
      anatomically described for rat cerebral arteries, a dilator function for these
      nerves has eluded investigators when using isolated vessels. Rat middle cerebral
      arteries (MCAs) were isolated, pressurized, and electrically stimulated. The
      resting diameter of the MCAs after pressurization was 233 +/- 4 microns (n = 17)
      in one study. The MCAs showed a frequency-dependent dilation when stimulated.
      Maximum dilation (25-30% increase in diameter) occurred at a frequency of 8-16
      Hz. Removal of endothelium or glibenclamide (10(-5) M), a blocker of ATP
      sensitive potassium channels, had no effect on the dilations. The dilations were
      completely blocked with NG-nitro-L-arginine methyl ester (L-NAME) (10(-5) M), a
      general NOS inhibitor, and cold storage (24 h). The inhibition by L-NAME could be
      reversed by the addition of 10(-8) M L-arginine, the active precursor of NOS.
      Furthermore, 7-nitroindazole (10(-4) M), an inhibitor specific for the neuronal
      isoform of NOS, reduced the dilations by 43% (P < 0.05). Transections of nerve
      bundles originating from the sphenopalatine ganglia at the ethmoidal foramen
      blocked the dilations produced by electrical stimulations. We conclude that rat
      cerebral arteries have functionally intact perivascular nerves that dilate by
      releasing nitric oxide.

PMID- 9277553
TI  - Natural osmolyte trimethylamine N-oxide stimulates tubulin polymerization and
      reverses urea inhibition.
AB  - The natural osmolyte trimethylamine N-oxide (TMAO) is one of the methylamine
      compounds often accumulated by diverse organisms in response to osmotic stress
      and/or to compensate for the deleterious effects of urea. Tubulin polymerization
      is promoted by TMAO. At 1 M TMAO, tubulin polymers are produced with properties
      expected of normal steady-state microtubules (MT): polymerization is reversed by
      exposure to cold or the antimitotic drug podophyllotoxin, a critical
      concentration for polymerization at 30 degrees C of 1.5 microM is found, and the
      morphology of the polymers in electron micrographs is typical of MT and ribbons,
      or open MT. At 2 M TMAO, polymerization is very rapid and hyperstable polymers
      are formed. These are resistant to cold-induced depolymerization although still
      sensitive to podophyllotoxin inhibition. A lower critical concentration of 0.7
      microM is observed, and electron micrographs reveal MT, ribbons, and other
      polymer forms not usually stable, such as splayed protofilaments. Inhibition of
      tubulin polymerization by low concentrations of urea (Sackett, D. L., B.
      Bhattacharyya, and J. wolff. Biochemistry 33: 12868-12878, 1994) is largely
      reversed by the presence of TMAO at one-half the molarity of urea, the
      physiological ratio observed in cartilaginous fishes. Other methylamines,
      including betaine, dimethylglycine, glycine, and sarcosine, failed to stimulate
      MT polymerization or protect against urea inhibition. Trimethylamine, taurine and
      glycylglycine inhibit polymerization. TMAO did not interfere with binding of MT
      associated proteins (MAP) and protected both tubulin assembly and MAP binding
      from urea.

PMID- 9277554
TI  - Inhibition of brain interleukin-1 attenuates sleep rebound after sleep
      deprivation in rabbits.
AB  - It is hypothesized that interleukin-1 (IL-1) is involved in physiological sleep.
      If this hypothesis is correct, inhibition of IL-1 should attenuate sleep
      responses after sleep deprivation. We tested the effect of
      intracerebroventricular or intravenous injection of an IL-1 inhibitor, an IL-1
      receptor fragment (IL-1RF), on sleep rebound after sleep deprivation in rabbits.
      Six hours of total sleep deprivation significantly increased non-rapid eye
      movement sleep (NREMS) and enhanced electroencephalogram slow-wave activity
      during NREMS. Intracerebroventricular treatment with the IL-1RF (50 micrograms)
      significantly attenuated the sleep responses after sleep deprivation.
      Furthermore, 1.0 mg/kg i.v. injection of the IL-1RF significantly suppressed
      spontaneous NREMS in rabbits that were not sleep deprived. However, intravenous
      administration of the IL-1RF (1.0 mg/kg) failed to attenuate the sleep responses
      following the 6-h sleep deprivation period. These results support the hypothesis
      that central pools of IL-1 are important for physiological sleep regulation.

PMID- 9277556
TI  - Influence of age on the sympathetic neural adjustments to alterations in systemic
      oxygen levels in humans.
AB  - We tested the hypothesis that aging influences the regulation of sympathetic
      nervous system activity (SNA) and arterial blood pressure during alterations in
      systemic O2 levels in humans. To accomplish this, we performed direct
      (intraneural) measurements of SNA to skeletal muscle (MSNA) in 10 young and 7
      older healthy normotensive men during room air breathing (normoxic-control),
      moderate isocapnic hypoxemia [15 min of 10% fractional inspired O2 (FIO2)], and
      hyperoxemia (10 min of 50% FIO2). After hypoxemia, arterial O2 saturation (SaO2)
      declined similarly in the young and older men. MSNA (burst frequency and total
      minute activity) increased significantly (P < 0.05) in both groups. The
      magnitudes of the absolute increases in MSNA and the delta MSNA/delta SaO2 were
      not significantly different in the young and older men; however, because of
      higher normoxic baseline levels, the percentage increases in burst frequency were
      smaller (P = 0.02) and those for total minute activity tended to be smaller (P =
      0.11) in the older men. Arterial blood pressure increased modestly (P < 0.05) and
      similarly in both groups, although the older men demonstrated a smaller increase
      in heart rate. After hyperoxemia [corrected], SaO2 increased and MSNA decreased
      (both P < 0.05) similarly in the young and older men. Arterial blood pressure did
      not change significantly from normoxic control levels in either group; however, a
      small (P < 0.05) reduction in heart rate was observed in both groups. In
      conclusion, aging does not obviously influence the regulation of absolute levels
      of MSNA or arterial blood pressure during alterations in systemic O2 levels in
      healthy men, although older men demonstrate a smaller percentage increase in MSNA
      from their elevated baseline levels, as well as an attenuated tachycardia in
      response to acute hypoxemia. As such, the present results are consistent with our
      previous findings on aging and sympathocirculatory control during other types of
      acute stress in humans.

PMID- 9277555
TI  - Prevention of diet-induced obesity in transgenic mice overexpressing skeletal
      muscle lipoprotein lipase.
AB  - Transgenic (Tg) FVB/N mice were produced that overexpress human lipoprotein
      lipase (LPL) in skeletal muscle using the muscle creatine kinase promoter and
      enhancers. It was hypothesized that, by overexpressing LPL in muscle, high fat
      feeding-induced obesity would be prevented by diverting lipoprotein-derived
      triglyceride fatty acids away from storage in adipose tissue to oxidation in
      muscle. Mice were examined both at 6 wk of age before high fat (HF) feeding and
      at 19 wk of age after 13 wk of HF (46.1% fat) or high carbohydrate (HC) feeding
      (11.5% fat). At 6 wk in heterozygous Tg mice, LPL was increased 11-fold in white
      muscle and 2.5-fold in red muscle, but not in cardiac muscle or spleen, brain,
      lung, kidney, or adipose tissue. Plasma triglycerides (mg/dl) were lower in Tg
      mice (87 +/- 7 vs. 117 +/- 7, P < 0.0001), and glucose increased (201 +/- 9 vs.
      167 +/- 8 mg/dl, P = 0.029). There were no differences in body weight between Tg
      and nontransgenic (nTg) mice; however, carcass lipid content (% body wt) was
      significantly decreased in male Tg mice at 6 wk (7.5 +/- 1.0 vs. 9.0 +/- 1.0%, P
      = 0.035). Body composition was not different in female Tg mice at 6 wk. Overall,
      when Tg mice were fed either a HC or HF diet for 13 wk, plasma triglycerides (P <
      0.001) and free fatty acids (P < 0.001) were decreased, whereas plasma glucose (P
      = 0.01) and insulin (P = 0.05) were increased compared with nTg mice. HF feeding
      increased carcass lipid content twofold in both male (10.3 +/- 1.1 vs. 21.4 +/-
      2.6%, HC vs. HF, P < 0.001) and female nTg mice (6.7 +/- 0.9 vs. 12.9 +/- 1.8%, P
      = 0.01). However, the targeted overexpression of LPL in skeletal muscle prevented
      HF diet-induced lipid accumulation in both Tg male (10.2 +/- 0.7 vs. 13.5 +/-
      2.2%, HC vs. HF, P = NS) and female Tg mice (6.8 +/- 0.6 vs. 10.1 +/- 1.4%, P =
      NS). The potential to increase LPL activity in muscle by gene or drug delivery
      may prove to be an effective tool in preventing and/or treating obesity in
      humans.

PMID- 9277557
TI  - Ethanol disrupts and decreases the regulated body temperature differentially in
      C57BL/6J and DBA/2J mice.
AB  - Two inbred mouse strains, C57BL/6J (B6) and DBA/2J (D2), were evaluated for
      effects of ethanol on thermoregulation. Continuous recording of core temperature
      (Tc) from undisturbed animals at an ambient temperature (Ta) of 27 degrees C
      indicated Tc was similar for both strains during active (approximately 38.0
      degrees C) and inactive (approximately 36.7 degrees C) periods. Ethanol
      injections of 1.5, 2.5, 3.5, and 4.5 g/kg in an environment where Ta rose and
      fell at 6-min intervals, reaching extremes of 14 and 42 degrees C, produced dose
      dependent falls in Tc for both strains. The changes in Ta produced fluctuations
      in Tc under all conditions. The amplitude of these fluctuations in Tc was used as
      a measure of physiological disruption. Dose-dependent increases in disruption
      were found for both strains. At a constant 26 degrees C Ta, ethanol produced dose
      related increases in tail temperature. Responses after ethanol administration
      were different for B6 and D2 mice. The results indicate regulated temperature is
      similar for B6 and D2 strains. Regulated temperature is decreased more by ethanol
      for B6 mice, whereas disruption of thermoregulation by ethanol is greater for D2
      mice.

PMID- 9277559
TI  - Magnesium kinetics in adolescent girls determined using stable isotopes: effects
      of high and low calcium intake.
AB  - Magnesium kinetics were measured in five adolescent girls who were participating
      in a calcium balance study. Two calcium levels were fed in a randomized crossover
      design. After an acclimation period, 26Mg was consumed orally and 25Mg was given
      intravenously, and then blood, urine, and feces were collected for 14 days. Total
      magnesium and percent enrichment were determined, and data were fitted to a eight
      compartment model. There was no significant difference between high and low
      calcium intakes for any of the parameters examined. Mean values for control (800
      mg/day) and high (1,800 mg/day) calcium intake were as follows: Mg intake, 305 +/
      30 and 286 +/- 9 mg/day; absorption (percent), 44 +/- 7 and 39 +/- 9; absorption
      (mg/day), 134 +/- 35 and 110 +/- 28; urinary excretion, 96 +/- 22 and 101 +/- 31
      mg/day; fecal excretion, 175 +/- 32 and 200 +/- 11 mg/day; and magnesium balance,
      13 +/- 35 and -34 +/- 48 mg/day, respectively. In conclusion, high calcium intake
      did not alter magnesium kinetics or balance in adolescent girls.

PMID- 9277558
TI  - Role of lysophosphatidic acid in endothelin-1- and hematoma-induced alteration of
      cerebral microcirculation.
AB  - Cerebral hematoma increases cerebrospinal fluid (CSF) endothelin-1 (ET-1).
      Inhibitors of ET-1 synthesis prevent this increment and hematoma-induced
      modification of cerebral arteriolar reactivity. We hypothesized that intrathecal
      ET-1 injection could 1) modify pial arteriolar reactivity similarly to hematoma;
      2) increase CSF lysophosphatidic acid (LPA), a potential contributor to altered
      cerebrovascular reactivity; and 3) reduce the level of adenosine 3',5'-cyclic
      monophosphate (cAMP) in the CSF. Either ET-1 (10(-7) M) or artificial CSF was
      injected over the left parietal cortex of newborn pigs. Four days later, cranial
      windows were implanted. CSF ET was increased from a basal level of 11 fmol/ml to
      18 fmol/ml 4 days after ET-1 injection, whereas CSF cAMP was reduced from 2,700
      to 950 fmol/ml. The mean diameter of pial arterioles was reduced 31%. In control
      animals, 10(-12) M ET caused dilation, and higher concentrations induced
      vasoconstriction. Four days after ET-1 injection topical ET-1 caused constriction
      instead of dilation at 10(-12) M, and constrictions at higher doses were
      enhanced. Norepinephrine-induced constrictions were potentiated in the ET-1
      injected group. Dilations to cAMP-dependent (but not independent) vasodilators
      were attenuated after ET-1. The concentration of the vasoconstrictor lipid
      mediator LPA increased approximately fourfold. Thus intrathecal injection of ET-1
      mimics hematoma-induced modification of cerebral vascular reactivity and increase
      in LPA production. The mechanism(s) of ET-1- and hematoma-induced modifications
      may involve LPA, which is known to contribute to the loss of dilator responses by
      inhibition of cAMP product on. The present study further suggests that ET-1
      together with LPA could be causing changes in cerebrovascular reactivity
      following cerebral hemorrhage. ET-1 stimulates the release of LPA from brain
      parenchyma independent of serum so that LPA could serve as a secondary mediator.

PMID- 9277560
TI  - Vasodilation and glomerular binding of adrenomedullin in rabbit kidney are not
      CGRP receptor mediated.
AB  - The polypeptide adrenomedullin (ADM) was infused systemically to conscious
      rabbits to elucidate its actions on overall circulation and especially the
      renovascular bed and the formation and/or release of hormones important for body
      fluid homeostasis, including adrenocortical steroids. ADM lowered mean arterial
      pressure from 71.5 +/- 3.2 to 64.7 +/- 3.2 mmHg only at the highest dose of 25
      pmol.min-1.kg-1 infused intravenously for 20 min and concomitantly induced
      tachycardia, possibly due to both baroreflex activation and direct
      cardiostimulatory effects. Renal blood flow (RBF) determined in rabbits
      chronically equipped with a perivascular ultrasonic flow probe increased from
      55.4 +/- 2.1 to 67.4 +/- 2.7 and from 58.2 +/- 3.5 to 75.2 +/- 6.0 ml/min at ADM
      infusions of 5 and 25 pmol.min-1.kg-1, respectively. The elevation in RBF
      persisted even in the presence of the calcitonin gene-related peptide (CGRP1
      receptor antagonist CGRP-(8-37). Of all osmoregulatory hormones tested, only
      corticosterone (Cort) plasma concentration increased in response to the highest
      ADM dose from 17.6 +/- 3.1 to 38.9 +/- 6.2 ng/ml, probably due to haroreflex
      activation. Subdepressor doses of ADM, however, caused a mild reduction in
      circulating Cort. Expression of functional high-affinity binding sites specific
      for ADM in vitro could be demonstrated for the renal artery and outer cortical
      glomeruli using 125I-labeled rat ADM as radioligand and determination of cellular
      adenosine 3',5'-cyclic monophosphate (cAMP) formation within the glomeruli. The
      ineffectiveness of CGRP-(8-37) to displace radiolabeled ADM from its binding
      sites, to inhibit ADM-induced glomerular cAMP formation, and to prevent ADM
      induced renal vasodilation supports the hypothesis of ADM altering renal
      hemodynamics by interacting with ADM- and not CGRP-specific membrane receptors.

PMID- 9277561
TI  - Selective breeding for diet-induced obesity and resistance in Sprague-Dawley
      rats.
AB  - In outbred Sprague-Dawley rats, about one-half develop diet-induced obesity (DIO)
      on a diet relatively high in fat and energy (HE diet). The rest are diet
      resistant (DR), gaining weight and fat at the same rate as chow-fed controls.
      Here we selectively bred for high (DIO) and low (DR) weight gainers after 2 wk on
      HE diet. By the F5 generation, both male and female inbred DIO rats gained > 90%
      more weight than inbred DR rats on HE diets. Even on low-fat chow diet, DIO males
      were 31% and females were 22% heavier than their respective DR rats. Full
      metabolic characterization in male rats showed that weight-matched, chow-fed DIO
      prone rats had similar energy intakes and feed efficiency [body weight
      (kg0.75)/energy intake (kcal)] but 44% more carcass fat than comparable DR-prone
      rats. Their basal plasma insulin and glucose levels in the fed state were 70 and
      14% higher, respectively. But, when fasted, DIO-prone oral glucose tolerance
      results were comparable to DR-prone rats. Chow-fed DIO-prone males also had 42%
      greater 24-h urine norepinephrine levels than DR-prone males. During 2 wk on HE
      diet, DIO rats ate 25% more, gained 115% more weight, had 36% more carcass fat,
      and were 42% more feed efficient than comparable DR rats. Fasted HE diet-fed DIO
      rats developed frank glucose intolerance during a glucose tolerance test with 55
      and 158% greater insulin and glucose areas under the curve, respectively. Thus
      the DIO and DR traits in the outbred Sprague-Dawley population appear to be due
      to a polygenic pattern of inheritance.

PMID- 9277562
TI  - Central noradrenergic system modulates plasma interleukin-6 production by
      peripheral interleukin-1.
AB  - The role of the central noradrenergic system in systemic interleukin-6 (IL-6)
      production induced by intravenously administered recombinant human interleukin-1
      beta (IL-1 beta) was examined in rats. Pretreatment of rats
      intracerebroventricularly with 6-hydroxydopamine (6-OHDA, 100 or 200
      micrograms/rat) significantly attenuated the increase in plasma IL-6 levels
      caused by IL-1 beta (2 micrograms/kg i.v.). A modest inhibition of the IL-1 beta
      induced plasma IL-6 production was observed following pretreatment with prazosin
      (20 micrograms/rat i.c.v.) but not after administration of idazoxan or
      propranolol. There were no significant increases in the IL-6 content in the
      hypothalamus, medulla oblongata, and cortex of the brain after intravenous IL-1
      beta. Adrenalectomy produced an augmented plasma IL-6 response to intravenous IL
      1 beta, whereas chemical sympathectomy with intraperitoneal injection of 6-OHDA
      (50 or 100 mg/kg) decreased the IL-1 beta-induced plasma IL-6 levels. Nor
      epinephrine (NE), in the dose range 10(-6)-10(-4) M, significantly increased the
      IL-6 levels in the rat spleen lymphocyte culture media. At doses of 10(-9)-10(-7)
      M, NE enhanced the effect of IL-1 beta on the IL-6 release by spleen lymphocytes
      in a dose-dependent manner. These findings suggest that the plasma IL-6 response
      to intravenous IL-1 beta is partially mediated through the activation of the
      central noradrenergic system and a consequent increase in the sympathetic outflow
      to the peripheral tissues and that the NE released from the sympathetic terminals
      may function as a mediator and/or modulator to facilitate the synthesis/release
      of IL-6 in the sympathetic nerve-innervated organs.

PMID- 9277563
TI  - Individual variation in reentrainment after phase shifts of light-dark cycle in a
      diurnal rodent Octodon degus.
AB  - The rate and pattern of activity and temperature reentrainment was determined
      after 3-, 6-, and 9-h phase advances and phase delays in two groups of Octodon
      degus for whom phase response curves (PRCs) to light and dark pulses and free
      running periods (tau) in constant darkness and constant light had previously been
      determined [T.M. Lee and S. E. Labyak. Am. J. Physiol. 273 (Regulatory
      Integrative Comp. Physiol. 42): R278-R286, 1997.]. We predicted that individuals
      with light-pulse PRCs containing both significant phase delay and phase advance
      regions would phase delay more rapidly than individuals lacking significant phase
      delays after light pulses. We also expected that animals without a phase delay
      region in the light-pulse PRC would demonstrate more temporary circadian
      abnormalities during the period of reentrainment (periods of masking, bimodal
      patterns of activity, and abnormal phase relationships between activity and
      temperature). Degus with light-pulse PRCs containing both a significant phase
      delay and -advance region reentrained significantly faster and with fewer
      disrupted patterns of entrainment after 6- and 9-h phase delays than degus
      without phase-delay regions in the PRC. The rate of reentrainment after phase
      advances did not differ between animals with the two types of PRC except for
      temperature after a 6-h phase shift. Because animals with and without phase-delay
      regions in the light-pulse PRC had equivalent tau s, the interindividual
      variation in reentrainment is best explained by the fundamental differences in
      the light-pulse PRCs. The variation of rate and pattern of reentrainment for both
      groups of animals were reasonably predicted or explained by knowledge of the
      light-pulse and dark-pulse PRCs.

PMID- 9277564
TI  - Effect of carbon dioxide on autonomic cardiovascular responses to systemic
      hypoxia in conscious rats.
AB  - The contribution of the autonomic nervous system to the cardiovascular response
      to hypoxia with different levels of CO2 was investigated in conscious rats.
      Wistar rats were chronically instrumented for measurement of arterial blood
      pressure (ABP), electrocardiogram, and renal sympathetic nerve activity (RSNA).
      They were exposed to 1) hypocapnic hypoxia (Hypo), 2) isocapnic hypoxia (Iso),
      and 3) hypercapnic hypoxia (Hyper). Hypo caused a decrease in ABP, an increase in
      heart rate (HR) and RSNA, and a slight increase in plasma norepinephrine (NE).
      Iso caused no significant change in ABP or HR but did cause an increase in RSNA
      and plasma NE. Hyper caused an increase in ABP, a decrease in HR, and an increase
      in RSNA and plasma NE. In sinoaortic-denervated (SAD) rats, ABP and RSNA
      decreased and HR tended to decrease during Iso. SAD abolished the bradycardic
      response during Hyper. Atropine abolished the bradycardic response during Hyper,
      and HR tended to increase during all three kinds of hypoxia. In all three kinds
      of hypoxia, ABP and renal sympathetic nervous responses in atropine-treated rats
      were not significantly different from those in intact rats. These results
      indicate that Hypo causes sympathetic activation and parasympathetic inhibition
      while Iso and Hyper cause sympathetic and parasympathetic activation via
      peripheral chemoreceptors. The MABP-RSNA curve tended to shift to the left and
      the maximum gain of the baroreflex response tended to decrease during Hypo. In
      contrast, this curve shifted to the right and the maximum gain of the baroreflex
      response increased during Iso and Hyper, suggesting that baroreflex function is
      affected by arterial CO2 levels. We concluded that cardiovascular responses
      during hypoxia are modified by arterial Pco2 levels and mediated by the autonomic
      nervous system.

PMID- 9277565
TI  - Effects of small intestinal nutrient infusion on appetite and pyloric motility
      are modified by age.
AB  - The mechanisms responsible for the reduction in appetite and slowing of gastric
      emptying in older persons are unknown. The aims of this study were to evaluate
      the effects of aging on small intestinal regulation of appetite and pyloric
      motility. Eight healthy older (age 65-75 yr) and seven healthy young (age 20-34
      yr) male subjects received isocaloric (2.9 kcal/min) intraduodenal infusions of
      lipid and glucose for 120 min, each on separate days. During the intraduodenal
      infusions, perceptions of hunger, desire to eat, and fullness were assessed by
      visual analog scales. Pyloric motility (isolated pyloric pressure waves and tonic
      pyloric pressure) was measured by manometry during the intraduodenal lipid
      infusion. On each day, after completion of the intraduodenal nutrient infusion
      the subject was offered a buffet meal and food intake was quantified. Before
      intraduodenal nutrient infusions, sensations of hunger (P < 0.01) and desire to
      eat (P < 0.05) were less in the older compared with the young subjects. In the
      young, intraduodenal lipid suppressed hunger to a greater extent than
      intraduodenal glucose (P < 0.05). In older persons, neither intraduodenal
      nutrient infusion suppressed hunger. Intraduodenal lipid and glucose increased
      fullness in both age groups (P < 0.05 for both), with no significant difference
      between the two nutrients. There was no significant difference in food intake
      from the buffet meal between the elderly and young subjects. Intraduodenal lipid
      infusion stimulated phasic pyloric pressure waves in both age groups (P < 0.01
      for both), and this response was greater (P < 0.05) in older persons. There was
      an increase (P < 0.01) in tonic pyloric pressure during intraduodenal lipid
      infusion that was not significantly different between the two age groups. We
      conclude that the effect of small intestinal lipid infusion on hunger is
      attenuated, and the stimulation of phasic pyloric pressure waves increased in
      healthy older persons compared with healthy young males. Increased feedback from
      small intestinal nutrients does not appear to be responsible for the
      physiological anorexia of aging.

PMID- 9277566
TI  - Effect of hypothyroidism on adenylyl cyclase activity and subtype gene expression
      in brown adipose tissue.
AB  - Brown adipose tissue (BAT) expresses several adenylyl cyclase (AC) subtypes, and
      adrenergic stimulation selectively upregulates AC-III gene expression. Previous
      studies have described synergistic interactions between the sympathetic nervous
      system (SNS) and 3,5,3'-triiodothyronine (T3) on the regulation of gene
      expression in BAT. Because adrenergic stimulation also increases the activity of
      BAT type II thyroxine 5'-deiodinase (DII) and local T3 generation is important
      for many functional responses in BAT, we examined the effects of thyroid hormone
      status on the expression of various AC subtypes. Hypothyroidism selectively
      increased AC-III mRNA levels in BAT but not in white adipose tissue. Of the other
      subtypes examined, hypothyroidism did not alter AC-VI mRNA levels and slightly
      reduced AC-IX mRNA levels in BAT. The increase in AC-III expression was
      paralleled by an increase in forskolin-stimulated AC activity in BAT membranes.
      Sympathetic denervation of BAT abolished the increase in both AC activity and AC
      III mRNA expression produced by hypothyroidism, but did not affect the expression
      of other subtypes. Surgical denervation also prevented the induction of AC-III in
      the cold-stressed euthyroid rat, but injections of T3 failed to alter AC-III
      expression in intact or denervated BAT. Our results indicate that T3 does not
      directly affect expression of AC-III. Rather, hypothyroidism increases BAT AC-III
      expression indirectly via an increase in sympathetic stimulation. Furthermore,
      our results strongly indicate that the increase in AC activity in hypothyroid BAT
      is due to increased expression of AC-III.

PMID- 9277567
TI  - Short-day weight loss and effect of food deprivation on hypothalamic NPY and CRF
      mRNA in Djungarian hamsters.
AB  - The effect of food deprivation on hypothalamic neuropeptide Y (NPY) and
      corticotropin-releasing factor (CRF) gene expression in the Djungarian hamster
      was quantified by in situ hybridization. Hamsters housed in short days (SD) for
      18 wk decreased body weight by 40% and exhibited 200% increases in both NPY and
      CRF mRNA when deprived of food for 24 h. Prior gonadectomy in long days (LD)
      affected neither basal gene expression nor the induction of gene expression by
      food deprivation. Gene expression in juvenile LD hamsters similar in body weight
      to SD animals was relatively insensitive to food deprivation of either 24- or 48
      h duration or to subsequent refeeding. In juvenile hamsters, food deprivation for
      24 but not 48 h decreased ob (obese) gene expression in inguinal but not
      epididymal white adipose tissue; ob mRNA levels were restored by refeeding. All
      food-deprived hamsters had reduced plasma insulin concentrations, but plasma
      cortisol was only elevated in SD food-deprived animals. NPY gene expression was
      also increased after daily dexamethasone injections in adult LD hamsters. These
      results suggest that the neuroendocrine consequences of food deprivation in SD
      Djungarian hamsters are determined by some factor other than absolute body mass
      such as the size of adipose tissue reserves.

PMID- 9277568
TI  - Febrile responsiveness of vagotomized rats is suppressed even in the absence of
      malnutrition.
AB  - The repeatedly observed attenuation of fever in vagotomized rats has been
      accepted as evidence of an essential role of vagal afferents in the transduction
      of pyrogenic signals from the periphery to the brain. If, however, the general
      condition of a vagotomized animal is poor (the usual case) and accompanied by
      malnutrition and body mass loss (common complications of vagotomy), the febrile
      responsiveness can be suppressed not because of the lack of vagal afferentation,
      but rather secondarily to a malnutrition-associated thermogenic incompetence. In
      the present study, we addressed this dilemma. Male Wistar rats were subjected to
      subdiaphragmatic vagotomy (or sham surgery) and, 24 days later, catheterized in
      the jugular vein. Postsurgically, the rats were closely watched and fed highly
      palatable food. Their febrile responsiveness [colonic (Tc) and tail skin (Tsk)
      temperature responses] to Escherichia coli lipopolysaccharide (LPS: 1
      microgram/kg i.v.) was tested on day 27 postvagotomy. To verify the completeness
      of vagotomy, each rat was food deprived for 24 h and then euthanized; its
      stomach's evacuatory function was assessed by weighing the organ. One month
      postsurgery, both food consumption and body mass of the vagotomized rats (33 +/-
      2 g/day and 313 +/- 4 g, respectively) were similar to the control values (30 +/-
      1 g/day and 315 +/- 8 g). In the sham rats, LPS induced a monophasic Tc rise of
      0.5 +/- 0.3 degree C at 70 min postinjection (peak), preceded by a fall in Tsk.
      Neither this Tsk fall (tail skin vasoconstriction) nor the resultant fever
      occurred in the vagotomized rats; at 70 min, Tc change was -0.1 +/-0.1 degree C.
      The gastric mass (4.1 +/- 0.5 g in the vagotomized vs. 1.8 +/- 0.1 g in sham
      rats) indicated the effectiveness of vagotomy. In sum, although the vagotomy
      associated malnutrition was successfully prevented with special perioperative
      care, the vagotomized animals still did not respond to LPS with fever.
      Malnutrition is, therefore, unlikely to constitute the main reason of the febrile
      irresponsiveness of vagotomized rats.

PMID- 9277569
TI  - Cold defense mechanisms in vagotomized rats.
AB  - Subdiaphragmatically vagotomized rats cannot mount a febrile response to pyrogens
      and are believed to have severe thermoregulatory deficiencies. We addressed the
      issue of thermoeffector competence of vagotomized rats by asking three questions.
      In Expt. 1 we asked, can vagotomized rats readily recruit tail skin
      vasoconstriction in the course of a moderate cold exposure? In Expt. 2 the
      question was, can brown adipose tissue (BAT) thermogenesis readily be activated
      in vagotomized rats (e.g., in response to a tail pinch)? In Expt. 3, we
      investigated the question: can vagotomized rats elevate their body temperature in
      response to ephedrine (a drug of high hyperthermizing potential) to the same
      extent as sham-operated controls? Rats were vagotomized or sham operated and
      implanted with a catheter into the jugular vein and a thermocouple into the
      interscapular BAT. To prevent the common complications of vagotomy, special
      perioperative care was given. During experiments, colonic, tail skin, and BAT
      temperatures (Tc, Tsk, and TBAT, respectively) were measured. The vagotomized
      animals were well nourished and had a body mass (325 +/- 6 g) similar to that of
      the controls (338 +/- 6 g). In Expt. 1, in response to external cooling (15
      degrees C, 1 h), the vagotomized (n = 30) and sham-operated (n = 31) rats
      recruited tail skin vasoconstriction at close values of both Tc (37.84 +/- 0.08
      and 37.97 +/- 0.07 degrees C) and Tsk (33.16 +/- 0.17 and 33.18 +/- 0.18 degrees
      C, respectively). In Expt. 2, tail pinch-associated stress in vagotomized rats
      resulted in a sharp rise in the TBAT-Tc gradient by 0.3-1.0 degree C. In Expt. 3,
      ephedrine administered intravenously (whether in a 5 or 35 mg/kg dose) evoked
      similar hyperthermic responses in the vagotomized and sham-operated rats: a
      moderate (approximately 2.5 degrees C) Tc rise in the low dose and a
      "supramaximal" (approximately 5.0 degrees C) rise in the high dose. In sum, the
      answer to all three questions asked is yes. Vagotomized rats, at least when well
      nourished, exhibit no signs of thermoeffector deficiency. It is, therefore, not
      effector incompetence but rather vagal deafferentation per se that can explain
      the febrile irresponsiveness of vagotomized rats.

PMID- 9277570
TI  - NMDA receptor coagonist glycine site: evidence for a role in lateral hypothalamic
      stimulation of feeding.
AB  - To investigate the role of the glycine coagonist binding site on the N-methyl-D
      aspartate (NMDA) receptor in feeding control, we injected the glycine site
      antagonist 7-chlorokynurenic acid (7-CK) into the lateral hypothalamus (LH) of
      satiated rats before LH injection of NMDA, 7-CK (10-44 nmol) blocked the 6- to 10
      g eating response elicited by NMDA. This block was reversed by LH pretreatment
      with glycine, arguing for a specific action at the glycine site. In contrast to
      the suppression produced by high doses, 7-CK at 0.1 nmol enhanced NMDA-elicited
      eating. For examination of behavioral specificity, 7-CK was injected into the LH
      before kainic acid (KA) or DL-alpha-amino-3-hydroxy-5-methylisoxazole-propionic
      acid (AMPA). 7-CK at a dose of 0.1 nmol suppressed feeding elicited by KA or
      AMPA, but at 10 nmol it suppressed eating elicited by AMPA while enhancing eating
      elicited by KA. Finally, bilateral LH injection of 7-CK effectively suppressed
      eating produced by fasting. These findings support a role for the NMDA receptor
      coagonist glycine site in LH regulation of eating behavior.

PMID- 9277571
TI  - Social cues modulate free-running circadian activity rhythms in the diurnal
      rodent, Octodon degus.
AB  - Two experiments assessed the effects of social cues and daily disturbance on the
      circadian locomotor activity rhythms of Octodon degus housed in constant
      darkness. In experiment 1, females in free-running conditions were housed alone
      or with entrained female partners ("donors") in cages on either side of a mesh
      barrier. Donors were removed daily and entrained to 1 h of light, and as a
      control, the cages of singly housed animals were rustled daily coincident with
      donor removal and replacement. None of the animals housed alone entrained to
      daily disturbances presented during the active phase, and seven of eight degus
      failed to show changes in the circadian period (tau) or phase of their rhythms.
      In contrast, although the presence of entrained donors did not elicit full
      entrainment of free-running rhythms, five of six animals demonstrated partial
      entrainment for 5-12 days (of 30 days), four of six altered phase of activity
      onset, and six of six lengthened tau of circadian rhythms. In experiment 2,
      females whose free-running circadian activity rhythms were at least 10 h out of
      phase were housed together in pairs. None of the pairs demonstrated mutual
      synchronization of their activity rhythms, although 8 of 12 degus modified phase
      of activity onset and 9 of 12 animals altered tau. We conclude social information
      in the absence of light, is sufficient for partial entrainment and for changes in
      tau and phase of free-running rhythms in this diurnal rodent.

PMID- 9277572
TI  - Effect of substance P on C1 and other bulbospinal cells of the RVLM in neonatal
      rats.
AB  - Sixty-two bulbospinal neurons were recorded in the rostral ventrolateral medulla
      (RVLM) of neonatal rats using patch electrodes. Sixty-one percent of the recorded
      neurons identified by histology contained tyrosine-hydroxylase (C1 cells).
      Substance P increased the spontaneous firing rate of all recorded cells but had
      no effect on spike configuration. The peptide depolarized neurons that were
      silenced by injection of hyperpolarizing current and increased their input
      resistance. All cells (n = 12) were activated by a neurokinin (NK)1 receptor
      agonist but most were unaffected by an NK2- or an NK2-selective compound. In
      voltage clamp, substance P produced a current that was linearly related to the
      membrane voltage. This current reversed polarity close to the potassium
      equilibrium potential in 11 of 23 cells. It reversed at more hyperpolarized
      potentials or not at all in the rest of the cells. In conclusion, substance P
      upregulates the intrinsic discharge rate of C1 and other putative
      sympathoexcitatory cells in neonatal rats. This effect is mediated via NK1
      receptors. The depolarization is mediated by a reduction in resting potassium
      conductance and possibly by an additional cationic conductance. These results
      support the possibility that substance P could play a role "in vivo" in setting
      the basal level of discharge of the vasomotor cells of RVLM and therefore in
      regulating sympathetic vasomotor tone.

PMID- 9277573
TI  - Trigeminal and chemoreceptor contributions to bradycardia during voluntary dives
      in rats.
AB  - This study investigates the importance of chemoreceptive and trigeminal
      information during voluntarily initiated diving in rats. The heart rate responses
      to simulated diving are unaffected by chemoreceptor drive [McCulloch, P.F., and
      N. H. West. Am. J. Physiol. 263 (Regulatory Integrative Comp. Physiol. 32): R1049
      R1056, 1992] but are reversibly eliminated by infusion of glutamate receptor
      antagonists into the spinal trigeminal nuclei [McCulloch, P. F., I. A. Paterson,
      and N. H. West. Am. J. Physiol. 269 (Regulatory Integrative Comp. Physiol. 38):
      R669-R677, 1995]. To investigate the role of chemoreceptor drive in conscious
      dives, rats were made hypercapnic, hyperoxic, or hypoxic predive. The role of
      trigeminal input was explored by infusing the glutamatergic antagonists D-2-amino
      7-phosphoheptanoic acid and 6,7-dinitroquinoxaline-2,3-dione into the region of
      the trigeminal nuclei. The alteration of arterial blood gases predive had no
      effect on diving bradycardia. Trigeminal blockade reduced the intensity of the
      bradycardia but did not abolish it. Chemoreceptor input does not play a
      significant role in determining heart rate during conscious diving in rats. The
      attenuation, rather than abolition, of bradycardia on trigeminal blockade
      suggests either that we achieved incomplete blockade or that an additional
      spectrum of sensory inputs not present in simulated diving is important in
      determining the underwater heart rate during conscious diving in rats.

PMID- 9277574
TI  - Neuropeptide stimulation of the nitric oxide signaling pathway in Drosophila
      melanogaster Malpighian tubules.
AB  - Activation of the nitric oxide (NO) and guanosine 3', 5'-cyclic monophosphate
      (cGMP) signaling pathway stimulates fluid secretion by the Drosophila
      melanogaster Malpighian tubule. The neuropeptide cardioacceleratory peptide 2b
      (CAP2b) has been previously shown to stimulate fluid secretion in this epithelium
      by elevating intracellular cGMP levels. Therefore, it was of interest to
      investigate if CAP2b acts through NO in isolated tubules and thus presumably
      through stimulation of a tubule NO synthase (NOS). We show here by reverse
      transcription polymerase chain reaction that Drosophila NOS (dNOS) is expressed
      in Malpighian tubules. Biochemical assays of NOS activity in whole tubules show
      that CAP2b significantly stimulates NOS activity. Additionally, fluid secretion
      and cyclic nucleotide assays show that CAP2b-induced elevation of intracellular
      cGMP levels and fluid secretion rates are dependent on the activation of a
      soluble guanylate cyclase. Treatment of tubules with a specific NOS inhibitor
      abolishes the CAP2b-induced rise in intracellular cGMP levels. These data
      indicate that CAP2b stimulates NOS and therefore, endogenous NO production,
      which, in turn, stimulates a soluble guanylate cyclase. This is the first
      demonstration of stimulation of an endogenous NOS by a defined peptide in
      Drosophila.

PMID- 9277575
TI  - Improved method for single-bolus kinetic measurements using a noncleared
      reference indicator.
AB  - After intravenous injection of a tracer as a single bolus, its concentration
      decreases as it mixes with the plasma, disperses throughout the circulation, and
      enters body pools. Kinetic values that are dependent on early concentrations may
      be in considerable error because mixing is not instantaneous throughout the
      circulation, and this problem is particularly acute in the mammalian fetus, with
      its distinctive circulatory pattern. To minimize this error, a method was
      developed in which the noncleared reference tracer 125I-labeled albumin was
      injected together with a representative, rapidly cleared metabolite 14C-labeled
      palmitic acid, and the former was used to correct for mixing delay. A total of 19
      disappearance curves were studied after intravenous injection into seven near
      term fetal sheep. Kinetic values were calculated with and without correction for
      mixing delay. Taking account of mixing delay increased the calculated volume of
      distribution 41% [from 44 +/- 4 (SE) to 62 +/- 3 ml/kg, P < 0.001], increased
      plasma clearance rate 13% (from 41 +/- 2 to 47 +/- 1 ml-min-1.kg-1, P < 0.002),
      decreased the rate constant for irreversible loss 26% (from 1.05 +/- 0.07 to 0.78
      +/- 0.04 min-1, P < 0.001), and increased the calculated effective half-life 26%
      (0.71 +/- 0.06 to 0.90 +/- 0.05 min, P < 0.001). Thus use of the additional
      reference marker significantly altered calculated results and provided values
      believed to more accurately describe rapid disappearance from the central mixing
      compartment into metabolic pools.

PMID- 9277576
TI  - Two types of leptin-responsive gastric vagal afferent terminals: an in vitro
      single-unit study in rats.
AB  - In vitro gastric vagal afferents' (GVAs) unit activities were recorded from the
      ventral GVA nerve strands in rats. The responsiveness of 16 GVA terminals to
      close intra-arterial injection of vehicle (0.1 ml), leptin (350 pmol), and
      cholecystokinin (CCK)-8 (10 pmol) was analyzed to generate a spike count-versus
      time histogram. Data of 5-min spike counts before and after each treatment were
      normalized by dividing the latter by the former. A quotient (Q) > 1 indicates an
      excitatory effect, Q < 1 indicates an inhibitory effect, and Q close to 1
      indicates no effect. Two types of GVA terminals were identified. Type 1 (n = 8)
      responded to leptin with Q > 1; CCK-8 pretreatment did not consistently alter
      leptin sensitivity. In contrast, Type 2 (n = 8) responded to leptin with Q < 1 or
      close to 1, and CCK-8 pretreatment increased the leptin sensitivity so that the
      terminals responded to subsequent leptin with Q > 1. These data suggest that Type
      1 and Type 2 GVA terminals may provide afferent neural signals, which, in turn,
      will be involved in body weight and food intake control systems, respectively.

PMID- 9277577
TI  - Atrial and pulmonary endothelin mRNA is increased in a canine model of chronic
      low cardiac output.
AB  - Chronic thoracic inferior vena caval constriction (TIVCC) is a model of low
      cardiac output congestive heart failure (CHF), in which pulmonary and atrial as
      well as circulating endothelin (ET) are increased. ET is a potent vasoconstrictor
      and mitogenic peptide whose circulating concentrations are increased in severe
      human and experimental CHF. To date, an increase in ET production at key sites in
      CHF remains controversial. Therefore, the current study was designed to determine
      cardiac and pulmonary ET-1 mRNA in an experimental model of CHF produced by TIVCC
      in which avid sodium retention, intense vasoconstriction, and elevation of
      circulating ET-1 occur as in human CHF. Experiments were conducted in normal dogs
      and dogs with 7 days of TIVCC. Cardiac and pulmonary ET-1 mRNA were measured by
      quantified densitometry of Northern blots. Plasma and tissue (cardiac and
      pulmonary) ET-1 immunoreactivity were determined by radioimmunoassay. Cardiac and
      pulmonary tissue localization of ET-1 were determined by immunohistochemical
      staining. Plasma ET-1 was significantly increased in TIVCC compared with normal
      dogs. ET-1 mRNA was detectable in normal canine atria, ventricle, and lung. ET-1
      mRNA was significantly increased in TIVCC compared with normal dogs in both
      atrial and pulmonary tissues without alternations in ventricular ET mRNA. Atrial
      and pulmonary tissue concentrations of ET-1 also were markedly elevated in TIVCC
      compared with normal dogs. Immunohistochemical staining of atrial and pulmonary
      tissues for ET-1 demonstrated that the increased ET immunoreactivity was
      localized to atrial myocytes and pulmonary epithelial cells. These studies
      support a role for the heart and lung in the increased production of ET-1 in CHF.
      The current studies also suggest that ET-1 may have important autocrine and
      paracrine actions in cardiopulmonary regulation in experimental CHF.

PMID- 9277578
TI  - Mechanisms of chloride transport in the proximal tubule.
AB  - The major fraction of filtered Cl- is reabsorbed in the proximal tubule. An
      important component of Cl- reabsorption is passive and paracellular, driven by
      the lumen-negative potential difference in the early proximal tubule and the
      outwardly directed concentration gradient for Cl- in the later proximal tubule.
      Evidence suggests that a significant additional component of NaCl reabsorption in
      the proximal tubule is active and transcellular. Cl-/formate and Cl-/oxalate
      exchangers have been identified as mechanisms of uphill Cl- entry across the
      apical membrane. For steady-state Cl- absorption to occur by these mechanisms,
      formate and oxalate must recycle from lumen to cell. Recent studies indicate that
      recycling of formate occurs by H(+)-coupled formate transport in parallel with
      Na+/H+ exchange, whereas oxalate recycling takes place by oxalate/sulfate
      exchange in parallel with Na(+)-sulfate cotransport. The predominant route for Cl
      exit across the basolateral membrane is via Cl- channels. Unresolved issues
      include the adequacy of formate recycling to sustain Cl- absorption by Cl
      /formate exchange, the existence and contributions of additional mechanisms for
      apical Cl entry and basolateral Cl- exit, and the relative magnitudes of
      transcellular and paracellular transport under physiological conditions. In
      addition, the molecular identification and mechanisms of regulation of the Cl
      /formate and Cl-/oxalate exchangers remain to be defined.

PMID- 9277579
TI  - Role of protein kinase C in beta 2-adrenoceptor function in cultured rat proximal
      tubule epithelial cells.
AB  - Renal sodium excretion is regulated by the adrenergic system. We recently
      demonstrated the presence of functional beta 2-adrenoceptors (beta 2-AR) in
      cultured rat proximal tubule epithelial cells beta 2-AR activation resulted in
      increases in Na-K-adenosinetriphosphatase (Na-K-ATPase) activity and
      transcellular sodium transport as a consequence of increased apical sodium entry.
      The purpose of this study was to determine the role of protein kinase C (PKC) on
      beta 2-AR-dependent increases in Na-K-ATPase activity and sodium transport in
      proximal tubules. To determine the effect of PKC on basal function, cultured rat
      proximal tubule cells were exposed to phorbol 12-myristate 13-acetate (PMA). PMA
      increased apical Na entry (+/-80%), decreased Na-K-ATPase activity (+/-25%), and
      prevented increases in Na-K-ATPase activity after sodium entry facilitation with
      monensin. Decreases in Na-K-ATPase activity were associated with decreases in
      sodium transport (+/-30%). To determine whether beta 2-AR function was transduced
      by PKC, PKC activity was measured in cells exposed to the selective beta 2-AR
      agonist metaproterenol. Metaproterenol caused increases in PKC activity, which
      were blocked by a beta 2-AR but not by a beta 1-AR-receptor antagonist. beta 2-AR
      dependent increases in apical Na entry, Na-K-ATPase activity, and sodium
      transport were blocked by calphostin C or staurosporine. To determine whether PKC
      had additional effects on beta 2-AR function, cells were exposed to
      metaproterenol and PMA. Metaproterenol-induced increases in Na-K-ATPase activity
      and sodium transport were blocked by PMA. In conclusion, beta 2-AR-mediated
      increases in Na-K-ATPase activity and sodium flux are transduced by PKC acting
      through increases in apical Na entry. However, activation of PKC by phorbol
      esters inhibits beta 2-AR-dependent increases in Na-K-ATPase activity and sodium
      transport.

PMID- 9277580
TI  - Flow versus pressure in the control of renin release in conscious dogs.
AB  - In Goldblatt hypertension, renal artery stenosis reduces renal arterial pressure
      (RAP) and renal blood flow (RBF) and thereby increases plasma renin activity
      (PRA) levels. Although it is clear that reduction in RAP stimulates renin, the
      decrease in RBF may contribute to higher PRA as well. However, it has hitherto
      never been possible to dissociate a decrease in RBF from a concomitant decrease
      in RAP. To overcome this restriction, we used two protocols. 1) RAP was reduced
      in a single step to 70 +/- 0.2 mmHg (N = 8). RBF followed the sudden fall in RAP
      within 15 s but subsequently took on initial levels. In contrast, renal venous
      PRA increased from 0.95 +/- 0.22 to 5.6 +/- 1.4 ng angiotensin I.ml-1.h-1 (P <
      0.05) and remained at higher values even after RBF had regained control
      conditions. 2) Resonance between RAP and RBF was induced by superimposing slow
      sinusoidal RAP waves with a period length of 450 s (N = 9), leading to a phase
      shift of roughly 180 degrees (time delay, 241 +/- 12 s), i.e., RBF was maximal at
      minimal RAP. Under these conditions, renin release was only dependent on
      decrements in RAP (delay of only 27 +/- 8 s). In conclusion, RBF played no major
      role in renin release.

PMID- 9277581
TI  - Unexpected protection of glomerular mesangial cells from oxidant-triggered
      apoptosis by bioflavonoid quercetin.
AB  - Bioflavonoid quercetin is known as an anti-cancer agent that induces apoptosis of
      tumor cells. Currently, however, little is understood about the effect of this
      drug on the function of normal cells. In this report, we address an unexpected,
      novel action of quercetin against apoptosis. Pretreatment with quercetin
      protected mesangial cells from hydrogen peroxide (H2O2)-induced apoptosis. A
      similar effect was observed in other cell types including LLC-PK1 epithelial
      cells and NRK49F fibroblasts. To explore the molecular mechanisms involved, we
      tested the effect of quercetin on c-Jun/activator protein-1 AP-1), the crucial
      mediator for H2O2-initiated apoptosis. Northern blot analysis revealed that
      quercetin suppressed the c-jun expression by H2O2. This was correlated with
      blunted activation of 12-O-tetradecanoylphorbol 13-acetate response element (TRE)
      in response to H2O2. These results suggested that quercetin inhibited apoptosis
      via intervention in the c-Jun/AP-1 pathway. To further investigate the action of
      quercetin, its effect on tyrosine kinases was studied. Immunoblot analysis
      revealed that H2O2 induced tyrosine phosphorylation. Quercetin inhibited this
      process in a dose-dependent manner. Inactivation of tyrosine kinases was an event
      upstream of c-Jun/AP-1, because tyrosine kinase inhibitors suppressed both
      activation of c-Jun/AP-1 and induction of apoptosis by H2O2. These findings
      elucidated the novel action of quercetin as an apoptosis inhibitor. This
      cytoprotective effect was found to be via suppression of the tyrosine kinase-c
      Jun/AP-1 pathway triggered by oxidant stress.

PMID- 9277582
TI  - Downregulation of aquaporin-2 parallels changes in renal water excretion in
      unilateral ureteral obstruction.
AB  - In bilateral ureteral obstruction, both aquaporin-2 (AQP2) levels and urinary
      concentrating capacity are markedly reduced. However, the mechanisms involved in
      AQP2 downregulation are unknown. In rats with unilateral ureteral obstruction
      (UUO) the relative role of intrarenal and systemic factors can be evaluated.
      Semiquantitative immunoblotting revealed a marked decrease in AQP2 in obstructed
      kidneys to 23 +/- 7% (n = 9) of sham levels. This downregulation persisted 24 h
      after release of UUO. Furthermore, there was a significant but less extensive
      downregulation of AQP2 in the nonobstructed kidneys to 75 +/- 7% (n = 9) of sham
      levels. Consistent with impairment of collecting duct water reabsorption, free
      water clearance was greatly elevated in the obstructed kidneys (-2 +/- 1
      microliter-min-1.kg-1, determined immediately after release) and only moderately
      elevated in nonobstructed kidneys (-44 +/- 5 microliters.min-1.kg-1) compared
      with sham-operated controls (-59 +/- 3 microliters.min-1.kg-1). Also AQP2 mRNA
      levels were reduced in obstructed kidneys. Immunocytochemistry confirmed the
      marked decrease in AQP2 expression in obstructed kidneys. In nonobstructed
      kidneys AQP2 was predominantly found in intracellular vesicles, which together
      with the reduced expression and elevated free water clearance strongly suggests a
      role of AQP2 in the observed compensatory diuresis from nonobstructed kidneys.
      The much lower AQP2 protein and mRNA levels in obstructed vs. nonobstructed
      kidneys are consistent with intrarenal factors playing a major role for
      downregulation of AQP2.

PMID- 9277583
TI  - Adhesion of hydroxyapatite crystals to anionic sites on the surface of renal
      epithelial cells.
AB  - Adhesion of microcrystals that nucleate in tubular fluid to the apical surface of
      renal tubular cells could be a critical step in the formation of kidney stones,
      20% of which contain hydroxyapatite (HA). HA crystals bound rapidly to monolayer
      cultures of monkey kidney epithelial cells (BSC-1 line), used to model the
      surface of the nephron, in a concentration-dependent manner. Adhesion was blocked
      by diverse polyanions including heparin, pentosan polysulfate, polyaspartate, and
      polyglutamate, as well as many found in tubular fluid such as chondroitin
      sulfates A and B, heparan sulfate, citrate, nephrocalcin, and osteopontin. The
      polycations cetylpyridinium chloride and cationized ferritin, as well as the
      cationic dyes alcian blue, polyethylenimine, and brilliant blue R, also inhibited
      adhesion of HA crystals, as did specific lectins including Triticum vulgaris
      (wheat germ agglutinin). Anions that inhibited adhesion of crystals appeared to
      act on the crystal surface, whereas cations and lectins exerted their effect on
      the cell. Treatment of cells with neuraminidase inhibited binding of crystals,
      suggesting that anionic cell surface sialic acid residues function as HA crystal
      receptor sites that can be blocked by specific cations or lectins. Adherence of
      HA crystals to cells of another renal line (MDCK) and, to 3T3 fibroblasts was
      also inhibited by heparin, polyaspartate, alcian blue, and T vulgaris lectin,
      suggesting that these crystals bind to analogous molecules on the surface of
      different types of cells. These results suggests that the structure, quantity,
      and/or function of soluble anions in tubular fluid, as well as those anchored to
      the cell surface, could be critical determinants of HA crystal retention in the
      nephron and the subsequent formation of a renal stone.

PMID- 9277584
TI  - Expression of carbonic anhydrase IV in carbonic anhydrase II-deficient mice.
AB  - Chronic metabolic acidosis (CMA) in the rabbit upregulates carbonic anhydrase
      (CA) IV in the proximal convoluted tubule (PCT). This study was designed to
      assess CA IV expression in a model of CMA in the mouse, i.e., congenital
      deficiency in CA II [CA(II)D]. In female CA(II)D mice, CA IV specific activity
      but not CA IV immunoreactivity was upregulated in the renal cortex, specifically
      in microdissected PCTs. Western blot analysis showed higher expression of CA IV
      immunoreactive protein in renal membranes from males than in those from females.

PMID- 9277585
TI  - Proximal tubular fluid, kidney, and plasma levels of angiotensin II in
      hypertensive ren-2 transgenic rats.
AB  - The present study was performed to assess the plasma and kidney levels of
      angiotensin I (ANG I) and ANG II during prehypertensive (4- to 5-wk old),
      development (6- to 8-wk old), and maintenance (10- to 12-wk old) phases of
      hypertension in pentobarbital-anesthetized transgenic rats [TGR; strain name:
      TGR(mRen2)27] and age-matched transgene-negative Hannover Sprague-Dawley rats
      (HanSD). At 4-5 wk, mean arterial pressures of TGR were not different from those
      of HanSD (110 +/- 5 vs. 114 +/- 4 mmHg). However, mean arterial pressures of 6-8
      wk and 10-12 wk TGR were higher than those of HanSD (179 +/- 3 vs. 110 +/- 6 and
      173 +/- 5 vs. 116 +/- 3 mmHg, respectively; P < 0.01 in both cases). Plasma ANG
      II levels in 4-5 wk and 6-8 wk TGR were not different from those in HanSD (70 +/-
      11 vs. 66 +/- 7 and 60 +/- 8 vs. 48 +/- 12 fmol/ml, respectively). However,
      plasma ANG II levels in 10-12 wk TGR were higher than those in HanSD (125 +/- 26
      vs. 38 +/- 12 fmol/ml, P < 0.01). Kidney ANG II levels in 4-5 wk, 6-8 wk, and 10
      12 wk TGR averaged 370 +/- 57, 247 +/- 16, and 562 +/- 86 fmol/g, respectively,
      values not different from those in HanSD. In additional studies performed on 6-8
      wk TGR and HanSD, multiple free-flow proximal tubular fluid collections were
      obtained and pooled for each animal. In these experiments, mean arterial
      pressures of the 10 TGR and 7 HanSD studied averaged 178 +/- 9 and 129 +/- 3 mmHg
      (P < 0.01), respectively. The ANG II concentration in proximal tubular fluid
      obtained from TGR averaged 5.6 +/- 2.1 pmol/ml (n = 10), a value not different
      from that in proximal tubular fluid collected from HanSD (5.3 +/- 2.8 pmol/ml, n
      = 7). However, the ANG II contents of the micropunctured left kidney and the
      nonmicropunctured right kidney of TGR were lower than those in HanSD (690 +/- 95
      vs. 1,374 +/- 210 and 659 +/- 119 vs. 1,303 +/- 196 fmol/g, respectively; P <
      0.01 in both cases). The present findings indicate that proximal tubular fluid of
      hypertensive TGR contains nanomolar concentrations of ANG II and that proximal
      tubular fluid, plasma and kidney ANG II levels in anesthetized hypertensive TGR
      are not markedly suppressed compared with those in normotensive control rats.

PMID- 9277586
TI  - Posttranscriptional upregulation of Na(+)-K(+)-ATPase activity in newborn guinea
      pig renal cortex.
AB  - We measured Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) activity and
      subunit abundance in renal cortical homogenates and basolateral membranes (BLM)
      from fetal, newborn, and adult guinea pigs. Pump specific activity increased four
      to fivefold in cortical homogenates and BLM during the transition from fetus to
      newborn. Immunoblots of BLM showed that alpha- and beta-subunit abundance
      increased four- to seven- and fourfold, respectively, during the transition from
      fetus to newborn. Immunoblots of cortical homogenates revealed similar
      developmental patterns, with newborns having 3.5-fold (alpha) and 2.3-fold (beta)
      greater subunit abundances than fetuses. Therefore, the bulk of the postnatal
      increase in BLM-Na(+)-K(+)-ATPase abundance resulted from increased pump
      production or decreased pump degradation, rather than from redistribution of
      pumps from intracellular pools. Despite the developmental increase in alpha- and
      beta-subunit protein levels, newborn guinea pig kidneys had only 1.4- to 2.1-fold
      greater alpha 1-subunit mRNA abundance and only a 1.5-fold greater beta 1-subunit
      mRNA abundance than fetal kidneys. These results demonstrate large increases in
      renal cortical Na(+)-K(+)-ATPase specific activity and protein abundance
      immediately after birth. These increases, which appear to result largely from
      posttranscriptional upregulation, may play an important role in mediating the
      rapid postnatal increase in tubular NaCl reabsorption.

PMID- 9277588
TI  - Afferent arteriolar responses to ANG II involve activation of PLA2 and modulation
      by lipoxygenase and P-450 pathways.
AB  - Activation of angiotensin receptors activates phospholipase A2 (PLA2) in various
      tissues, resulting in the release of arachidonic acid and formation of vasoactive
      metabolites. The present study examined the role of the lipoxygenase and
      cytochrome P-450 pathways by evaluating the effects of PLA2, cyclooxygenase,
      lipoxygenase, and epoxygenase inhibition on the afferent arteriolar responses to
      angiotensin II (ANG II) and norepinephrine in the vitro perfused rat
      juxtamedullary nephron preparation. ANG II (0.01-100 nM) resulted in a dose
      dependent afferent arteriolar vasoconstriction ranging from 3 +/- 1 to 32 +/- 2%
      (n = 47). Norepinephrine at 0.01, 0.1, and 1.0 microM also decreased afferent
      arteriolar diameter by 5 +/- 1, 17 +/- 1, and 34 +/- 2%, respectively (n = 43).
      In the presence of arachidonyl trifluoromethyl ketone (AACOCF3, 20 microM), a
      PLA2 inhibitor, afferent arteriolar vasoconstriction to ANG II (100 nM) was
      attenuated, and the diameter decreased by 23 +/- 4% (n = 7). The cyclooxygenase
      inhibitor, indomethacin (10 microM), and the cyclooxygenase-2 inhibitor, NS-398
      (10 microM), did not affect the afferent arteriolar response to ANG II. The
      lipoxygenase inhibitor biacalein (1 microM) attenuated the afferent arteriolar
      response to ANG II, and vessel diameter decreased by 11 +/- 5% (n = 6) in
      response to 100 nM ANG II. On the other hand, miconazole (1 microM), a selective
      epoxygenase inhibitor, enhanced the afferent arteriolar vasoconstriction to 100
      nM ANG II. 17-Octadecynoic acid (17-ODYA, 1 microM), an inhibitor of hydroxylase
      and epoxygenase metabolism of arachidonic acid, also increased the responsiveness
      of the afferent arteriole. PLA2, lipoxygenase, or cytochrome P-450 inhibition had
      no effect on the afferent arteriolar vasoconstriction to norepinephrine. The
      afferent arteriolar vasoconstrictor response to norepinephrine (0.1 microM) was
      enhanced by indomethacin or NS-398, and diameter decreased by 25 +/- 3% and 28 +/
      4%, respectively. Results of this study suggest that metabolites of the
      cyclooxygenase pathway attenuate the afferent arteriolar vasoconstrictor effect
      of norepinephrine. Furthermore, these data suggest that activation of PLA2 is
      involved in part of the afferent arteriolar response to ANG II and that
      metabolites of the lipoxygenase pathway augment and metabolites of the
      epoxygenase pathway attenuate the afferent arteriolar vasoconstrictor effect of
      ANG II.

PMID- 9277587
TI  - Cloning of rat and mouse aquaporin-2 gene promoters and identification of a
      negative cis-regulatory element.
AB  - The promoters of rat and mouse aquaporin-2 (AQP-2) genes were cloned and compared
      with that of human genes. Nucleotide identity up to -593 bp was 62%, and
      consensus sequences such as TATA box and adenosine 3',5'-cyclic monophosphate
      responsive element were conserved. Deoxyribonuclease I footprint assay revealed a
      footprinted region at -210 to -184 bp in rat AQP-2 gene promoter produced by
      nuclear extract from nonexpressing (liver) tissue. The sequence of this region
      included a GATA motif but otherwise showed no homology with any other previously
      known cis-elements. Electromobility shift assay and ultraviolet cross-linking
      analysis confirmed that specific binding proteins to this element were present in
      kidney, spleen, and liver and that these proteins were distinct from GATA
      factors. Both deletion and mutation of this cis-element abolished the protein DNA
      binding and increased promoter activity in in vitro reporter gene assay using rat
      cultured hepatocyte Ac2F cells, suggesting the negative regulatory role of this
      cis-element. These results indicate that tissue-specific expression of AQP-2 gene
      may in part be regulated by this novel negative acting cis-element.

PMID- 9277590
TI  - Monoclonal antibodies for high-resolution localization of NHE3 in adult and
      neonatal rat kidney.
AB  - Previous immunochemical studies have shown that NHE3 is an apical Na+/H+
      exchanger in some renal epithelia. The purpose of the present study was to
      develop high-affinity, isoform-specific monoclonal antibodies (MAbs) that would
      be useful for carrying out high-resolution immunocytochemical studies of NHE3 in
      the adult and neonatal mammalian kidney. Three MAbs were developed to a fusion
      protein containing amino acids 702-832 of rabbit NHE3. Specificity was
      established by immunoblotting membranes from NHE-deficient LAP cells that had
      been transfected with either NHE1,-2, -3, or -4. With the use of high-resolution
      immunocytochemical techniques, NHE3 was found in vesicles in the apical cytoplasm
      of proximal tubule cells, as well as in the apical plasma membrane of the
      proximal tubule, and in both the thin and thick limbs of the loop of Henle. When
      localized in the 1-day-old rat kidney, NHE3 was first detected in the late stages
      of the S-shaped body. In later stages of nephron development, the pattern of NHE3
      staining was similar to that seen in the adult. This study demonstrates 1) the
      specificity of three MAbs for Na+/H+ exchanger isoform NHE3; 2) NHE3 is present
      in an intracellular vesicular compartment in cells of the proximal tubule,
      consistent with possible regulation by membrane recycling; and 3) NHE3 is
      expressed on the apical membrane in early stages of the developing nephron.

PMID- 9277589
TI  - Role of Rho and myosin phosphorylation in actin stress fiber assembly in
      mesangial cells.
AB  - Treatment of renal glomerular mesangial cells with adenosine 3',5'-cyclic
      monophosphate (cAMP)-elevating agents induces actin stress fiber disassembly,
      myosin light chain (MLC) dephosphorylation, loss of adhesion to the substratum
      and cell shape change [J. I. Kreisberg and M. A. Venkatachalam. Am. J. Physiol.
      251 (Cell Physiol. 20): C505-C511, 1986]. Thrombin and vasopressin block the
      effects of cAMP. Because these agents are known to promote stress fiber formation
      via the small GTP-binding protein Rho, we investigated the effect of an activated
      variant of Rho on the response to cAMP elevation. Microinjecting V14-Rho
      completely blocked the effect of cAMP elevation on cell shape and the actin
      cytoskeleton, whereas inactivating Rho with botulinum C3 exoenzyme induced stress
      fiber disruption and cell retraction that was indistinguishable from that caused
      by elevations in intracellular levels of cAMP. Disruption of actin stress fibers
      by cAMP has previously been ascribed to MLC dephosphorylation; however, both C3
      and cytochalasin D also caused dephosphorylation of MLC, whereas blocking MLC
      dephosphorylation failed to block the cAMP-induced loss of actin stress fibers.
      We conclude that Rho can modulate the effects of cAMP elevation and suggest that
      MLC dephosphorylation may be a consequence of actin stress fiber disassembly.

PMID- 9277591
TI  - Inducible expression of bcl-2 by the lac operator/repressor system in MDCK cells.
AB  - The lac operator/repressor-inducible system was utilized to dissect the
      biological consequences of human bcl-2 gene expression in Madin-Darby canine
      kidney (MDCK) cells. Cells were made transgenic for a constitutively expressed
      lacI gene, encoding lac repressor, and the bcl-2 gene that had been inserted
      downstream of a simian virus 40 (SV40) promoter containing the lac operator
      sequence. The expression of the bcl-2 gene could therefore be repressed to basal
      level by binding of lac repressor to the lac operator sequence in proximity to
      this SV40 regulatory region and be specifically activated by administration of
      the lactose analog isopropyl-beta-D-thiogalactoside (IPTG). We showed that
      expression of bcl-2 gene could be induced by 0.01 mM IPTG, and the maximal
      induction was obtained at 1 mM. With the treatment of IPTG, the Bcl-2 protein
      could be induced within 6 h. Moreover, the IPTG-inducible expression of Bcl-2
      protein is a reversible process. Finally, functional assays revealed that IPTG
      induced expression of bcl-2 gene conferred partial or complete resistance to
      homeless cell death or confluent cell death, respectively. The inducible
      expression system should be particularly useful for dissecting the effect of bcl
      2 in phenotypic or morphological changes of MDCK cells.

PMID- 9277592
TI  - Membrane potential measurements in renal afferent and efferent arterioles:
      actions of angiotensin II.
AB  - An adaptation of the in vitro perfused hydronephrotic rat kidney model allowing
      in situ measurement of arteriolar membrane potentials is described. At a renal
      perfusion pressure of 80 mmHg, resting membrane potentials of interlobular
      arteries (22 +/- 2 microns) and afferent (14 +/- 1 microns) and efferent
      arterioles (12 +/- 1 microns) were -40 +/- 2 (n = 8), -40 +/- 1 (n = 45), and -38
      +/- 2 mV (n = 22), respectively (P = 0.75). Using a dual-pipette system to
      stabilize the impalement site, we measured afferent and efferent arteriolar
      membrane potentials during angiotensin II (ANG II)-induced vasoconstriction. ANG
      II (0.1 nM) reduced afferent arteriolar diameters from 13 +/- 1 to 8 +/- 1
      microns (n = 8, P = 0.005) and membrane potentials from -40 +/- 2 to -29 +/- mV
      (P = 0.012). ANG II elicited a similar vasoconstriction in efferent arterioles,
      decreasing diameters from 13 +/- 1 to 8 +/- 1 microns (n = 8, P = 0.004), but
      failed to elicit a significant depolarization (-39 +/- 2 for control; -36 +/- 3
      mV for ANG II; P = 0.27). Our findings thus indicate that resting membrane
      potentials of pre- and postglomerular arterioles are similar and lie near the
      threshold activation potential for L-type Ca channels. ANG II-induced
      vasoconstriction appears to be closely coupled to membrane depolarization in the
      afferent arteriole, whereas mechanical and electrical responses appear to be
      dissociated in the efferent arteriole.

PMID- 9277593
TI  - Absence of tubuloglomerular feedback responses in AT1A receptor-deficient mice.
AB  - Experiments were performed in a recently generated strain of mice with an
      angiotensin II AT1A-receptor null mutation (M. Ito, M. I. Oliverio, P. J. Mannon,
      C. F. Best, N. Maeda, O. Smithies, and T. M. coffman. Proc. Natl. Acad. Sci. USA
      92: 3521-3525, 1995) to examine the effects of chronic AT1A receptor deficiency
      on tubuloglomerular feeback (TGF) responses. All animals were genotyped by
      polymerase chain reaction using primers designed to amplify sequences from the
      deleted AT1A gene and from the neomycin resistance gene. Normal mice (AT1A +/+)
      and mice heterozygous (AT1A +/-) and homozygous (AT1A -/-) for the gene
      disruption were anesthetized, and stop-flow pressures (PSF) were determined
      during changes in loop perfusion rate with previously established micropuncture
      methods. In five AT1A +/+ mice (26 tubules) mean PSF at zero loop flow was 37.2
      +/- 1.5 mmHg, falling to 28.2 +/- 1.9 mmHg at a flow of 45 nl/min (P < 0.0001).
      Flow rate causing the half-maximum response (V1/2) was 8.7 +/- 0.4 nl/min. In
      four AT1A +/- animals (19 tubules) mean PSF at zero flow was 39.9 +/- 2.4 mmHg,
      falling to 34.8 +/- 2.7 mmHg at 45 nl/min (mean V1/2 8.6 +/- 1.04 nl/min). In
      five AT1A -/- mice (24 tubules) PSF was not significantly affected by loop flow
      with PSF averaging 33.9 +/- 1.7 mmHg at zero flow and 33.2 +/- 1.6 mmHg at 45
      nl/min (not significant). Mean arterial blood pressures in the anesthetized and
      laparotomized mice were 91.8 +/- 2.2, 97.1 +/- 3, and 80.7 +/- 3.2 mmHg in the
      AT1A +/+, AT1A +/-, and AT1A -/- animals, respectively. Blood pressure responses
      to exogenous angiotensin II were greatly blunted in the AT1A -/- mice. We
      conclude that AT1A receptor-mediated effects of angiotensin II are in essential
      component of TGF responsiveness under chronic conditions. Our studies show the
      feasibility of using complex micropuncture methods in mice, an approach that
      widens the potential of genetically altered mouse strains as experimental models.

PMID- 9277594
TI  - Hostility and the heart.

PMID- 9277595
TI  - Consent for transfusion.

PMID- 9277596
TI  - Developing high quality clinical databases.

PMID- 9277597
TI  - Do professions have a future?

PMID- 9277598
TI  - United States bans smoking on federal property.

PMID- 9277599
TI  - Britain has become less equal in death.

PMID- 9277600
TI  - Is this the end of research as we know it?

PMID- 9277601
TI  - Sporadic Creutzfeldt-Jakob disease in the United Kingdom: analysis of
      epidemiological surveillance data for 1970-96.
AB  - OBJECTIVE: To identify changes in the occurrence of Creutzfeldt-Jakob disease
      that might be related to the epidemic of bovine spongiform encephalopathy.
      DESIGN: Epidemiological surveillance of the United Kingdom population for
      Creutzfeldt-Jakob disease based on (a) referral of suspected cases by
      neurologists, neuropathologists, and neurophysiologists and (b) death
      certificates. SETTING: England and Wales during 1970-84, and whole of the United
      Kingdom during 1985-96. SUBJECTS: All 662 patients identified as sporadic cases
      of Creutzfeldt-Jakob disease. MAIN OUTCOME MEASURES: Age distribution of
      patients, age specific time trends of disease, occupational exposure to cattle,
      potential exposure to causative agent of bovine spongiform encephalopathy.
      RESULTS: During 1970-96 there was an increase in the number of sporadic cases of
      Creutzfeldt-Jakob disease recorded yearly in England and Wales. The greatest
      increase was among people aged over 70. There was a statistically significant
      excess of cases among dairy farm workers and their spouses and among people at
      increased risk of contact with live cattle infected with bovine spongiform
      encephalopathy. During 1994-6 there were six deaths from sporadic Creutzfeldt
      Jakob disease in the United Kingdom in patients aged under 30. CONCLUSIONS: The
      increase in the incidence of sporadic Creutzfeldt-Jakob disease and the high
      incidence in dairy farmers in the United Kingdom may be unrelated to bovine
      spongiform encephalopathy. The most striking change in the pattern of Creutzfeldt
      Jakob disease in the United Kingdom after the epidemic of bovine spongiform
      encephalopathy is provided by the incidence in a group of exceptionally young
      patients with a consistent and unusual neuropathological profile. The outcome of
      mouse transmission studies and the future incidence of the disease in the United
      Kingdom and elsewhere, will be important in judging whether the agent causing
      bovine spongiform encephalopathy has infected humans.

PMID- 9277602
TI  - Commentary: age related exposure of patients to the agent of BSE should not be
      downplayed.

PMID- 9277603
TI  - Birth weight and risk of cardiovascular disease in a cohort of women followed up
      since 1976.
AB  - OBJECTIVE: To examine the association between birth weight and non-fatal adult
      cardiovascular disease while controlling for potential confounders such as
      socioeconomic group and adult lifestyle. DESIGN: Retrospective self report of
      birth weight in an ongoing longitudinal cohort of nurses followed up by postal
      questionnaire every two years. SETTING: Nurses' health study, a cohort of 121700
      women followed up since 1976. MAIN OUTCOME MEASURES: Non-fatal cardiovascular
      disease, including myocardial infarction, coronary revascularisation, and stroke.
      RESULTS: Among the 70297 women free of cardiovascular disease at baseline who
      reported birth weight in the 1992 questionnaire there were 1309 first cases of
      non-fatal cardiovascular disease. Increasing birth weight was associated with
      decreasing risk of non-fatal cardiovascular disease. There were 1216 first cases
      of non-fatal cardiovascular disease among women who were singletons and had been
      born full term; their relative risks adjusted for several cardiovascular risk
      factors were 1.49 (95% confidence interval 1.05 to 2.10) for birth weight < 2268
      g (< 5 lb 0 oz); 1.25 (0.98 to 1.61) for birth weight 2268-2495 g (5 lb 0 oz to 5
      lb 8 oz); 1.12 (0.98 to 1.27) for birth weight > 2495-3175 g (> 5 lb 8 oz to 7 lb
      0 oz); 1.00 (referent) for birth weight > 3175-3856 g (> 7 lb 0 oz to 8 lb 8 oz);
      0.96 (0.80 to 1.15) for birth weight > 3856-4536 g (> 8 lb 8 oz to 10 lb 0 oz);
      and 0.68 (0.46 to 1.00) for birth weight > 4536 g (> 10 lb 0 oz) (P value for
      trend = 0.0004). The inverse trend was apparent for both coronary heart disease
      and stroke. CONCLUSIONS: These data provide strong evidence of an association
      between birth weight and adult coronary heart disease and stroke.

PMID- 9277604
TI  - Birth weight and cognitive function in young adult life: historical cohort study.
AB  - OBJECTIVE: To examine the relation between birth weight and cognitive function in
      young adult life. DESIGN: Retrospective cohort study based on birth registry data
      and cognitive function measured during evaluation for military service. SUBJECTS:
      4300 Danish conscripts born between 1973 and 1975. MAIN OUTCOME MEASURES: Mean
      score in the Boerge Prien test of cognitive function; score is the number of
      correct answers to 78 questions and correlates with full scale intelligence
      quotient (IQ). RESULTS: Mean score in the Boerge Prien test increased from 39.9
      at a birth weight of < or = 2500 g to 44.6 at a birth weight of 4200 g even after
      adjustment for gestational age and length at birth, maternal age and parity, and
      other variables. Above a birth weight of 4200 g the test score decreased
      slightly. CONCLUSION: Birth weight is associated with cognitive performance in
      young adult life. Interference with fetal growth may influence adult cognitive
      performance.

PMID- 9277605
TI  - Association between raised body temperature and acute mountain sickness: cross
      sectional study.

PMID- 9277606
TI  - Age related dietary exposure to meat products from British dietary surveys of
      teenagers and adults in the 1980s and 1990s.

PMID- 9277607
TI  - Is histological examination of tissue removed by general practitioners always
      necessary? Before and after comparison of detection rates of serious skin
      lesions.
AB  - OBJECTIVES: To examine whether histological examination of all tissue removed by
      general practitioners in minor surgery increases the rate of detection of
      clinically important skin lesions, and to assess the impact of such a policy on
      pathologists' workload. DESIGN: Before and after comparison. SETTING: Stratified
      random sample of 257 general practitioner partnerships from the catchment areas
      of 19 English pathology laboratories. SUBJECTS: Tissue removed in minor surgery
      by general practitioners during the control period (September 1992 to February
      1993) and intervention period (September 1993 to February 1994). INTERVENTION:
      General practitioners referred to their local pathology laboratory all solid
      tissue removed in all minor surgery, irrespective of their previous policy. MAIN
      OUTCOME MEASURES: Numbers of specimens referred for histology by general
      practitioners during intervention and control periods; numbers of primary
      malignant melanomas, non-melanoma malignancies, premalignant lesions, and benign
      lesions. RESULTS: 257/330 partnerships participated (response rate 78%). During
      the intervention period 5723 specimens were sent, compared with 4430 during the
      control period. The referral rate increased by an estimated 1.34 specimens per
      1000 patient years (95% confidence interval 0.93 to 1.76, P < 0.0001). General
      practitioners sent 204 specimens that were malignant (including 16 malignant
      melanomas) in the control period and 188 that were malignant (including 15
      malignant melanomas) during the intervention period (change in total number of
      malignancies, -1.0 per 100,000 patient years (-5.9 to 3.8, non-significant).
      CONCLUSIONS: The intervention was associated with a substantial increase in
      laboratory workload, all of which was accounted for by increases in non-serious
      lesions. This observation should be taken into account when considering the
      merits of a policy requiring histological examination in every case.

PMID- 9277608
TI  - Fortnightly review. Environmental control systems for people with a disability:
      an update.

PMID- 9277609
TI  - ABC of mental health. Mental health in old age.

PMID- 9277610
TI  - Personal paper. Beliefs and evidence in changing clinical practice.

PMID- 9277611
TI  - How to read a paper. Statistics for the non-statistician. II: "Significant"
      relations and their pitfalls.
AB  - It is possible to be seriously misled by taking the statistical competence
      (and/or the intellectual honesty) of authors for granted. Some common errors
      committed (deliberately or inadvertently) by the authors of papers are given in
      the final box.

PMID- 9277612
TI  - Bovine spongiform encephalopathy threatens drugs in European Union.

PMID- 9277613
TI  - Delays in diagnosing oesophagogastric cancer. Attempts to reduce delays in
      diagnosis should be done in controlled trial.

PMID- 9277614
TI  - Delays in diagnosing oesophagogastric cancer. Small study showed no difference in
      delay with stage.

PMID- 9277615
TI  - Delays in diagnosing oesophagogastric cancer. Provision of endoscopy in primary
      care speeds diagnosis.

PMID- 9277616
TI  - Delays in diagnosing oesophagogastric cancer. Misconceptions exist over whether
      delay in diagnosis influences survival.

PMID- 9277617
TI  - Delays in diagnosing oesophagogastric cancer. Small study found that four fifths
      of delay was due to patients.

PMID- 9277618
TI  - Screening for mannose binding protein gene in routine practice is unnecessary.

PMID- 9277619
TI  - Sexual medicine. Integrated services for sexual health care are the way forward.

PMID- 9277620
TI  - Sexual medicine. Models of integrated sexual health services already exist.

PMID- 9277622
TI  - Safety in acupuncture. Rigorous accreditation schedule for acupuncture already
      exists.

PMID- 9277621
TI  - Sexual medicine. Genitourinary medicine clinics are an obvious place for
      treatment of sexual dysfunction.

PMID- 9277623
TI  - Safety in acupuncture. Core curriculum is important.

PMID- 9277624
TI  - Safety in acupuncture. Guidelines on practice of acupuncture exist.

PMID- 9277625
TI  - Association between voting patterns and mortality remains.

PMID- 9277626
TI  - Changes in laws are necessary to allow patients detained under Mental Health Act
      to vote.

PMID- 9277627
TI  - Discrimination of Alzheimer's disease and normal aging by EEG data.
AB  - Quantitative EEG results in Alzheimer's disease may be summarized by the term
      'slowing', i.e. slow frequencies (delta, theta) are increased and fast
      frequencies (alpha, beta) are decreased. But how can EEG data be used to
      discriminate AD patients from controls by means of EEG data? Discriminant
      analysis may produce false predictions using too many predictors, as is often the
      case in EEG studies. We studied 4 approaches to this problem: Classification by
      group means, stepwise discriminant analysis, a neuronal network using back
      propagation and discriminant analysis preceded by principal components analysis
      (PCA). A maximum of 86.6% correct classifications was reached using the last
      mentioned approach with EEG data alone. Including age as a moderator variable in
      a subgroup, 95.9% correct classifications were reached.

PMID- 9277628
TI  - Involvement of the claustrum in the convulsive evolution of temporal limbic
      seizure in feline amygdaloid kindling.
AB  - The effects of unilateral lesioning of the claustrum (CL) either prior to or
      following completion of amygdaloid (AM) kindling was examined in cats. CL
      lesioning ipsilateral to the kindling or the kindled AM caused the emergence of a
      mirror image pattern of expected or established AM onset convulsive seizure
      originating in the contralateral hemisphere. This finding suggests that: (1) the
      CL is involved in the convulsive evolution of AM onset non-convulsive limbic
      seizure; (2) an alternative transhemispheric route is available for the
      convulsive evolution of AM onset limbic seizure when the ipsilateral CL is
      disrupted; and (3) the CL is not critical for secondary convulsive
      generalization.

PMID- 9277629
TI  - Event-related potentials during memorization of spatial locations in the auditory
      and visual modalities.
AB  - Event-related potential (ERP) studies of working memory have used delayed S1-S2
      match-to-sample tasks in which S1 is held in memory for comparison with S2. ERP
      negativities in the S1-S2 interval have been interpreted either in terms of
      working memory operations, or in terms of general preparatory motor processing.
      Two experiments (N = 20 each) were carried out to explore the nature of ERP
      negativities in a visuospatial memory task and in an auditory spatial memory
      task, respectively. In the experimental condition, subjects had to memorize the
      location of S1 (S1-memorize) so as to respond whether S2 appeared in the same
      spatial location (S2-memorize). In the control condition, subjects were requested
      to ignore S1 (S1-passive), and to respond whether S2 matched or not a target
      location predetermined at the beginning of the trial block (S2-pressing). Results
      support the two main conclusions of Martin-Loeches et al. (Electroenceph. clin.
      Neurophysiol., 1994, 91: 363-373). Firstly, that the encoding into memory of
      spatial location is associated with an ERP negative wave over the brain areas
      putatively associated with the processing of sensory information (i.e. right
      parieto-occipital for the visual task; fronto-central and left temporal areas for
      the auditory task). Secondly, the P300 does not seem to be an important ERP
      feature related to spatial location encoding and retaining into memory. Despite
      the distinct scalp distribution of these memory-related, modality-specific ERP
      negativities, they also showed a considerable degree of temporal synchronicity
      across modalities.

PMID- 9277630
TI  - Event-related potential measures of information processing during general
      anesthesia.
AB  - To investigate the incidence and manner of auditory information processing during
      a state of presumed unconsciousness event-related brain potentials (ERPs) were
      studied in 41 patients undergoing cardiac surgery with propofol/alfentanil
      anesthesia. The ERPs were recorded during auditory oddball tasks administered
      before and within several periods of the operation. Mean nasopharyngeal
      temperature and anesthetic concentrations were determined for each intraoperative
      ERP recording epoch. During anesthesia ERP waves could still be observed up to
      500 ms after stimulus onset indicating that auditory information processing was
      not suppressed completely by the administered anesthetic agents. Relative to the
      preoperative recordings, the P1-N1-P2 complex was delayed and more positive going
      during anesthesia. Comparable changes in ERP morphology have been observed during
      Stage II-IV sleep, suggesting parallels in the mechanisms underlying early
      auditory processing in both states of reduced arousal level, possibly related to
      a selective reduction of a non-specific activity. N1 and P2 peak amplitudes were
      found to be larger for the deviant tones compared to the standard tones. These
      amplitude differences most likely reflect automatic detection of stimulus
      deviance, although it cannot be excluded entirely that they were due to
      differences in refractoriness. Anesthetic concentrations and nasopharyngeal
      temperature were found to be of minor significance for ERP control. It is
      suggested that ERPs could serve as intraoperative reference measures, providing
      the earliest evidence for auditory processing. This characteristic is important
      for validation of signals and techniques that are proposed to improve
      conventional monitoring of anesthesia with respect to detecting unintended
      awareness.

PMID- 9277632
TI  - N300, P300 and the emotional processing of visual stimuli.
AB  - Two components of the ERPs elicited by emotional visual stimuli, N300 and P300,
      were investigated. The emotional charge is explained through two dimensions:
      arousal (relaxing (R) or activating (A)) and valence (attractive (+) or repulsive
      (-)). Stimuli were slides of nudes (A+), human remains (A-), landscapes (R), and
      buildings (neutral (N)). The peculiar structure of the stimuli, along with a
      distracting task which allowed us to disguise the real aim of the experiment,
      helped to avoid a sort of 'relevance-for-task effect', mainly related to
      cognitive processes, which could explain P300 reactions in response to emotional
      visual stimuli found in several experiments. The ERPs were recorded from 32
      subjects at F3, Fz, F4, C3, Cz, C4, P3, Pz and P4. In contrast to previous
      studies, P300 did not show greater amplitudes in response to emotional stimuli
      than to N. N300 showed greater amplitudes in response to A+ at parietal sites,
      the greatest differences being those with respect to A-. No inter-hemispheric
      differences were found. N300 confirms its usefulness as a variable for studying
      emotional reactions to visual stimuli.

PMID- 9277631
TI  - Evidence of visual processing negativity with attention to orientation and color
      in central space.
AB  - The aim of this study was to determine whether the visual frontal processing
      negativity reported in our earlier paper (Karayanidis, F. and Michie, P.T.
      Electroenceph. clin. Neurophysiol., 1996, 99: 38-56) is related to selection of
      spatial location, or occurs regardless of the stimulus features used to define
      the target. Subjects were instructed to respond to infrequent target stimuli of a
      particular combination of orientation, color and size. All stimuli were presented
      at central fixation. Posteriorly, orientation selection enhanced P125 amplitude
      over the right hemisphere but neither orientation nor color selection had an
      effect on N190. Posterior selection negativities emerged for orientation, color
      and their conjunction. At anterior sites, widespread effects of orientation and
      color processing were evident. The effect of location selection on the anterior
      N1 seen in our previous study was not evident with orientation selection.
      Instead, selection of orientation, color and their conjunction resulted in P145
      250 frontally. Two later anterior negativities emerged. The early negativity
      (vPNe) was affected independently by orientation and color selection while the
      late negativity (vPNl) was affected only by selection of feature conjunction.
      Thus, the present results show that, like its auditory counterpart, the visual
      processing negativity occurs with a variety of stimulus classification features
      and is not exclusively related to spatial selection.

PMID- 9277633
TI  - A developmental study of the effect of temporal order on the ERPs elicited by
      novel environmental sounds.
AB  - Event-related brain potentials (ERPs) were recorded from 16 subjects in each of
      the following age groups, 5-7, 9-11, 14-16, and 20-28 years of age. Subjects
      performed a novelty oddball task, in which frequent, standard tones (80%
      probability) were intermixed with infrequent tones to which the subject responded
      (10%), along with 48 unique novel, environmental sounds (10%). Analyses focused
      on the effects of temporal order (either serial order within the block or block
      number) in interaction with age group on the ERPs to the novel sounds. The
      amplitude and scalp distribution of two ERP components were analyzed, the
      'novelty P3,' assumed to reflect aspects of the orienting response, and the P32,
      a component that may be synonymous with the P3b. Evidence suggests that the
      frontal aspect of the scalp distribution of the novelty P3 depends upon the
      integrity of the prefrontal cortex. Temporal order produced systematic (primarily
      linear) reductions in novelty P3 amplitude that were greater at frontal than
      posterior electrode sites. The P3(2) did not show consistent effects of temporal
      order. Both of these phenomena were highly similar for all four age groups. It is
      concluded that the brain's response to novelty is similar across a wide age
      range, involving a neural circuit with both frontal and posterior elements.

PMID- 9277634
TI  - Transcranial magnetic stimulation-induced changes in EEG and responses recorded
      from the scalp of healthy humans.
AB  - We determined the changes and responses in the electroencephalogram (EEG) induced
      by transcranial magnetic stimulation (TMS) of the scalp of five healthy men. The
      center of a circular coil was positioned at the vertex, and 80 stimulations were
      administered clockwise with the maximum output of electric current. To reduce
      stimulus artifacts, we created a circuit that blocked the input for 150 ms after
      stimulation. EEGs were recorded from F3,4, C3,4, P3,4, and T3,4. The following
      results were obtained: (1) slowing of the EEG was observed immediately (150 m)
      after each stimulation. The incidence of changes ranged from 25-80%; their
      duration ranged from 200-600 ms. (2). Electroencephalographic responses in the
      averaged form appeared as gentle positive waves. In some subjects and leads, 1 to
      3 negative peaks were fused. The methods used in the present study may be useful
      in evaluating the sensitivity to TMS of patients with stroke and other types of
      brain injury.

PMID- 9277635
TI  - To scale or not to scale: McCarthy and Wood revisited.
AB  - We dispute McCarthy and Wood's (1985) claim that some form of scaling should be
      applied routinely to ERP data before determining differences in scalp
      distributions between conditions (or groups). Their simulation study involved
      assumptions about the nature of the variability within each condition, most
      significantly that the standard deviations are identical at all electrodes,
      irrespective of the means. Alternative plausible assumptions may be proposed for
      which scaling is unnecessary. Furthermore, we show that the two main forms of
      scaling they proposed may distort or even completely eliminate real differences
      in scalp topography reflecting genuinely different underlying sources.

PMID- 9277636
TI  - A method to improve the latency estimation of the frequency-following potential
      (FFP).
AB  - If the latency of a noisy frequency-following potential (FFP) is estimated by
      determining the shift of the (periodical) cross-correlation function (CCF)
      between the stimulus and the FFP, the result may be unambiguous only within +/-1
      or +/-2 periods of the CCF, because the absolute maximum and adjacent local
      maxima may not be significantly different. Here we present a method to amplify
      this difference by applying amplitude modulated stimuli. Using this method we
      first illustrate the effect of the method by a simulation and then demonstrate
      its usefulness by measuring real FFPs and estimating their latencies.

PMID- 9277637
TI  - Outcome of nonimmune hydrops fetalis diagnosed during the first half of
      pregnancy.
AB  - OBJECTIVE: To evaluate the etiology and outcome of fetal hydrops of nonimmune
      origin diagnosed in utero during the first half of pregnancy. METHODS: We
      reviewed 45 cases of nonimmune fetal hydrops presenting between 11 and 17 weeks'
      gestation over a 4-year period. RESULTS: The median gestational age at diagnosis
      of fetal hydrops was 14 weeks. Placental edema was most commonly associated with
      generalized skin edema. Ascites was also observed in four cases, but no case
      presented with pleural or pericardial effusion. The fetal karyotype was abnormal
      in 35 cases (77.8%). Of the ten fetuses with a normal karyotype, four were
      classified as idiopathic, three had isolated atrioventricular septal defect, two
      were associated with maternal infection, and one had multiple pterygium. Fetal
      heart rate anomalies were found in both chromosomally normal and abnormal
      fetuses. All but one of the karyotypically abnormal pregnancies and five of ten
      euploid pregnancies were terminated. In all six pregnancies that continued,
      resolution occurred before mid-gestation. Three continuing euploid pregnancies
      resulted in fetal death, and only two had a normal outcome. CONCLUSION: Nonimmune
      fetal hydrops diagnosed before 18 weeks' gestation is associated with a higher
      incidence of aneuploidy than hydrops diagnosed during the second half of
      pregnancy. In most affected fetuses with a normal karyotype, spontaneous
      resolution occurred before 24 weeks' gestation, although the outcome was
      generally unfavorable.

PMID- 9277638
TI  - Two-dimensional echocardiography and Doppler ultrasound in managing obstetric
      patients.
AB  - OBJECTIVE: To test the usefulness of ultrasound-derived measurements of
      intracardiac filling pressures and cardiac performance in the noninvasive
      management of obstetric patients with an indication for hemodynamic monitoring.
      METHODS: We included patients with oliguria unresponsive to crystalloid boluses,
      with hypertension unresponsive to hydralazine, and at high risk for pulmonary
      edema who were determined to be candidates for invasive monitoring. They were
      first studied with two-dimensional echocardiography and Doppler ultrasound using
      a technique previously validated at our institution. Cardiac dimensions, filling
      pressures, and function were assessed at the bedside. Subsequently, management
      decisions were made based on these findings. RESULTS: Fourteen patients were
      studied. Two received a pulmonary artery catheter after noninvasive evaluation
      indicated a need for continuous monitoring. The 12 patients managed without the
      need for a pulmonary artery catheter included women with intractable hypertension
      (one patient), pulmonary edema (two patients), complex cardiac lesions (two
      patients), oliguria (five patients), intractable hypertension and oliguria (one
      patient), and unexplained dyspnea with peripheral arterial oxygen desaturation
      (one patient). Although some patients received as much as 8 L of crystalloid,
      none developed pulmonary edema or left ventricular failure. In all 12 cases, the
      ultrasound monitoring allowed successful noninvasive management of the patient.
      CONCLUSION: This pilot study suggests that two-dimensional echocardiography and
      Doppler examination may be an effective alternative to invasive monitoring in the
      management of selected pregnant patients.

PMID- 9277639
TI  - Three-dimensional ultrasound-assessed fetal thigh volumetry in predicting birth
      weight.
AB  - OBJECTIVE: To compare the accuracy of three-dimensional ultrasound-assessed fetal
      thigh volumetry in predicting birth weight with that of other commonly used
      formulas composed of biparietal diameter (BPD), abdominal circumference (AC), and
      femur length (FL) by two-dimensional ultrasound. METHODS: We assessed the thigh
      volume of 100 fetuses using three-dimensional ultrasound. Meanwhile, their BPD,
      AC, and FL were measured by two-dimensional ultrasound. All infants were
      delivered within 48 hours after the ultrasound examinations. From polynomial
      regression analysis, we generated a best-fit formula for the thigh volume to
      predict birth weight. The accuracy of this thigh-volume formula was compared with
      those of three formulas commonly used in the United States. In addition, another
      group of 50 fetuses was measured for prospective validation. RESULTS: The high
      volume assessed by three-dimensional ultrasound was highly correlated with birth
      weight (r = 0.89, n = 100, P < .0001). The best-fit formula for thigh volume to
      predict birth weight was linear, and it was superior to the other commonly used
      two-dimensional formulas in predicting birth weight. The predicting error (0 g),
      percent error (0.7%), absolute error (176.1 g), and absolute percent error (5.8%)
      of the thigh-volume formula were all smaller than those of the other formulas (n
      = 100, all P < .05). In addition, the thigh-volume formula predicted birth weight
      more accurately than the other two-dimensional formulas in the prospective
      validation group. The three-dimensional formula had smaller mean values of
      predicting error (38.6 g), percent error (1.5%), absolute error (160.0 g), and
      absolute percent error (5.1%) than the two-dimensional formulas (n = 50, all P <
      or = .001), as well as the smallest variances of the above errors (178.1 g, 5.6%,
      84.3 g, and 2.9%, respectively). CONCLUSION: The three-dimensional ultrasound
      assessed thigh volume has better accuracy in predicting birth weight than the
      commonly used formulas by two-dimensional ultrasound, and it may improve fetal
      weight prediction in clinical practice. However, a large-scale prospective
      validation study may be needed to confirm our conclusions.

PMID- 9277640
TI  - Effect of maternal meal ingestion on fetal renal artery resistance.
AB  - OBJECTIVE: To examine whether maternal meal ingestion affects the fetal
      circulation in uncomplicated pregnancies. METHODS: A simple crossover blinded
      study was designed for late uncomplicated singleton pregnancies. After overnight
      fasting, two different maternal meal states were tested. In one state, pregnant
      women had a standard 600-kcal breakfast at 8 AM (phase A). The other state
      consisted of maintaining fasting (phase B). Both states were assigned to each
      woman within 3 days in randomized order. Fetal Doppler studies of the umbilical,
      middle cerebral, and renal arteries and the descending aorta were performed at 7
      AM (the fasting state) and at 10 AM (the fed state or the continuous fasting
      state). RESULTS: Twenty women underwent the crossover study. Regardless of the
      maternal meal state, no significant change was observed in the pulsatility index
      (PI) of either the umbilical artery (n = 20), the middle cerebral artery (n =
      19), or the descending aorta (n = 15). However, the PI of the fetal renal artery
      decreased significantly after maternal meal ingestion (n = 14) (phase A, 2.36 +/-
      0.16 versus 2.09 +/- 0.33; P = .021). There was no such change in the PI after
      prolonged fasting (phase B, 2.44 +/- 0.32 versus 2.39 +/- 0.44; P = .75).
      CONCLUSION: Fetal renal artery resistance decreased after maternal meal ingestion
      in normally grown fetuses during late pregnancy. This decrease in the resistance
      may be associated with increased fetal urine production after maternal meals.

PMID- 9277641
TI  - Fetal laceration injury at cesarean delivery.
AB  - OBJECTIVE: To investigate the incidence of fetal laceration injury in cesarean
      delivery. METHODS: A retrospective review was conducted using a computer-based
      data coding system. All neonatal records were reviewed for infants delivered by
      cesarean during a 2-year period. Maternal records were reviewed in those cases of
      documented fetal laceration injury. The Fisher exact test was used when
      indicated. RESULTS: There were 904 cesarean deliveries performed during the study
      period; of these, 896 neonatal records (98.4%) were available for review.
      Seventeen laceration injuries were recorded (1.9%). The incidence of laceration
      appeared higher when the indication for cesarean was nonvertex (6.0% versus 1.4%,
      P = .02). One of 17 (5.9%) maternal records indicated the presence of the
      laceration of the fetus. CONCLUSION: Fetal laceration injury at cesarean delivery
      is not rare, especially when it is performed for nonvertex presentation. The
      minority of obstetric records show documentation of such lacerations, suggesting
      that this complication often may not be recognized by obstetricians.

PMID- 9277643
TI  - Validation of first-trimester telemedicine as an obstetric imaging technology: a
      feasibility study.
AB  - OBJECTIVE: To establish whether first-trimester obstetric ultrasonography
      interpreted by a live video telemedicine link is comparable to an established
      videotape review network in a low-risk patient population. METHODS: An integrated
      services digital network was established from three satellite offices to our
      central prenatal diagnostic center. All patients had a sonographic evaluation of
      the uterus, adnexa, and gestational sac recorded onto videotape by a trained
      sonographer. A live, interactive video telemedicine link was established, and a
      perinatologist directed the sonographer through the scan. Subsequently, a
      different perinatologist, blinded to the telemedicine interpretation, reviewed
      the original videotaped examination. The reports generated from both modalities
      then were compared by means of a score of 12 sonographic characteristics.
      RESULTS: The first 100 patients were included. The mean gestational age (+/
      standard deviation) was 8.9 +/- 2.3 weeks (range 5.7-14.4), and the mean duration
      for telemedicine scans was 7.8 +/- 2.9 minutes (range 3.8-20.1). Telemedicine and
      videotape review scores were the same in 95 cases, and the final diagnosis was
      identical in 98 cases. This study had 80% power to detect a 10% difference in
      diagnosis at a significance level of .05. The ability to detect abnormalities was
      equivalent using both systems. CONCLUSION: The interpretation of first-trimester
      obstetric ultrasonography using live video telemedicine is equivalent to a system
      of videotape review. Obstetric telemedicine may prove to be a useful tool for
      providing sonographic imaging for low-risk obstetric patients.

PMID- 9277642
TI  - The pediatric costs of strategies for minimizing the risk of early-onset group B
      streptococcal disease.
AB  - OBJECTIVE: To estimate the pediatric costs associated with the Centers for
      Disease Control and Prevention (CDC) guidelines for the management of infants
      born to mothers receiving intrapartum antimicrobial prophylaxis for prevention of
      early-onset group B streptococcal disease. METHODS: For an annual United States
      birth cohort of 3.95 million infants, we estimated the cost of pediatric care
      provided to full-term asymptomatic infants when pediatricians followed the CDC
      algorithm for the management of infants exposed to intrapartum antimicrobial
      prophylaxis under culture-based and risk factor-based maternal care approaches.
      We calculated the relative contribution of pediatric costs to the total costs of
      preventing a case of early-onset group B streptococcal sepsis. RESULTS: Total
      pediatric costs were $41 million for a culture-based approach and $33 million for
      a risk factor-based approach. Hospital and physician costs accounted for more
      than 78% of this total. The majority (over 95%) of the pediatric costs were
      associated with vaginal deliveries. Incorporating pediatric costs into previous
      cost-effectiveness analyses increased the cost per sepsis case averted by as much
      as 51% for culture-based strategies and by as much as 112% for risk factor-based
      strategies. Pediatric costs varied with the average length of stay for full-term
      infants and with the average cost of a hospital day. CONCLUSION: Substantial
      pediatric costs are associated with the implementation of an obstetric strategy
      for minimizing the risk of early-onset group B streptococcal disease. Such costs
      should be included in future cost-effectiveness analyses of different strategies
      for minimizing the risk of group B streptococcal disease in newborns.

PMID- 9277644
TI  - Transvaginal ultrasound in the prediction of preterm delivery: singleton and twin
      gestations.
AB  - OBJECTIVE: To compare, in singleton and twin pregnancies, the effectiveness of
      transvaginal ultrasound versus digital examination in predicting preterm delivery
      in women with suspected preterm labor. METHODS: Transvaginal ultrasound and
      pelvic examinations were performed on patients admitted with suspected preterm
      labor between 23 and 33 weeks' gestation. Ultrasound assessment of cervical
      length and the presence of funneling with fundal pressure were recorded for each
      patient, and the results were compared with dilatation and effacement as assessed
      by digital examination for the prediction of preterm delivery in the two groups
      (singletons and twins). RESULTS: One hundred sixty-two subjects were recruited
      (136 singletons and 26 twin pregnancies), with no significant demographic
      differences between the groups. Overall, 33% of the participants delivered
      preterm (27% of singletons, 62% of twins). Using receiver operating
      characteristics curves, the best cutoff points were 30 mm for endocervical length
      at ultrasound, 50% for effacement, and 1.5 cm for dilatation. Of these, the best
      predictor was endocervical length, which was a better predictor in singleton than
      in twin pregnancies. Of the potential predictors, including endocervical length,
      funneling, dilatation, and effacement, only endocervical length was an
      independent predictor of preterm delivery at less than 34 weeks' gestation for
      both singletons and twins by multiple logistic regression. When analyzed for
      delivery at less than 37 weeks' gestation, this relation held true for singletons
      but not twins. Endocervical length less than 30 mm had a sensitivity of 81% and
      75%, specificity of 65% and 30%, positive predictive value of 46% and 63%, and
      negative predictive value of 90% and 43% for singleton and twin pregnancies,
      respectively, in predicting spontaneous birth at less than 37 weeks' gestation.
      CONCLUSION: Between 23 and 33 weeks' gestation, transvaginal ultrasound
      assessment of endocervical length is superior to funneling and digital
      examination in predicting preterm delivery in patients who present with suspected
      preterm labor, and is a better predictor in singletons than in twins.

PMID- 9277645
TI  - Effects of autoantibodies on the course of pregnancy and fetal growth.
AB  - OBJECTIVE: To assess the effects of autoantibodies on the course of pregnancy and
      fetal growth. METHODS: One thousand one hundred seventy-nine healthy women with
      singleton gestations were screened in early pregnancy for seven kinds of
      autoantibodies: antithyroid microsomal antibody, antithyroglobulin antibody, two
      kinds of rheumatoid factor, antinuclear antibody, anti-DNA antibody, and
      antimitochondrial antibody. RESULTS: In 228 cases (19.3%), at least one
      autoantibody was found; however, overlap of autoantibodies in the same individual
      was unexpectedly rare, and only two cases were positive for as many as four
      autoantibodies. A significantly higher rate of spontaneous abortion was observed
      in antibody-positive subjects, especially those with antithyroid microsomal
      (10.4%) or antinuclear antibodies (16.0%), compared with all antibody-negative
      subjects (5.5%). There were no significant differences in any outcome assessed
      among subjects positive for antithyroglobulin antibody, anti-DNA antibody, or
      antimitochondrial antibody compared with all antibody-negative subjects. None of
      the seven autoantibodies affected the rates of preterm delivery, stillbirth,
      pregnancy-induced hypertension, malformation, or gender ratio. CONCLUSION:
      Antithyroid microsomal antibody and antinuclear antibody are the only
      autoantibodies that increase the abortion rate.

PMID- 9277646
TI  - Free beta-hCG subunit versus intact hCG in Down syndrome screening.
AB  - OBJECTIVE: To assess the ability of second-trimester maternal serum free beta-hCG
      to detect fetal Down syndrome and to compare free beta-hCG to intact hCG in the
      multiple-marker screening test for Down syndrome. METHODS: From our bank of
      stored maternal sera, we selected 40-50 samples from euploid pregnancies at each
      week of gestation from 14 to 20 weeks and 31 samples from Down syndrome
      pregnancies. Free beta-hCG was measured by enzyme-linked immunosorbent assay, and
      week-specific multiples of the median (MoM) were derived. The free beta-hCG Down
      syndrome detection and false-positive rates were determined. Free beta-hCG was
      then substituted for intact hCG in the multiple-marker screening test, and the
      Down syndrome detection and false-positive rates at various risk cutoffs were
      compared. RESULTS: The mean (+/-standard deviation) maternal age of all study
      samples was 35.6 +/- 5.3 years. The mean Down syndrome free beta-hCG MoM was
      significantly higher than the mean euploid MoM (2.4 +/- 1.1 versus 1.2 +/- 1.0; P
      < .001). A free beta-hCG level of at least 1.7 MoM identified 68% of Down
      syndrome pregnancies at a false-positive rate of 20%. When intact hCG was
      replaced with free beta-hCG in the multiple-marker screening test, a higher Down
      syndrome detection rate was achieved at a lower false-positive rate at each of
      several screen positive risk cutoffs. CONCLUSION: Elevated free beta-hCG levels
      identify Down syndrome pregnancies. Replacing intact hCG with free beta-hCG in
      the multiple-marker screening test results in a higher Down syndrome detection
      rate at a lower false-positive rate.

PMID- 9277647
TI  - Potential roles for gonadal steroids and insulin-like growth factor I during
      final cervical ripening.
AB  - OBJECTIVE: To determine whether gonadal steroids and insulin-like growth factor I
      influence the final cervical remodeling during parturition. METHODS: Cervical
      biopsies were obtained transvaginally before labor (n = 10) and after spontaneous
      cervical ripening and vaginal delivery (n = 20). Levels of estrogen and
      progesterone receptors, their messenger RNAs, insulin-like growth factor I
      messenger RNA, and serum estradiol and progesterone were measured. Collagen and
      proteoglycan concentrations and compositions were measured to estimate the degree
      of cervical ripeness. RESULTS: The concentrations of estrogen and progesterone
      receptors decreased in comparison with the clinically unripe cervix before labor.
      The median estrogen receptor concentration (range) decreased from 10 (2-18) to
      4.5 (2-14) fmol/mg protein (P < .01), and the progesterone receptor concentration
      from 105.5 (32-153) to 74 (30-115) fmol/mg protein (P < .05), whereas their
      messenger RNA levels were unchanged. The insulin-like growth factor I messenger
      RNA concentration declined from 16.1 (8.4-20.4) at term to 8.9 (1.5-18.5)
      amol/microgram DNA after parturition (P < .01). The collagen solubility by pepsin
      increased, but not significantly, and the collagen concentration was unchanged.
      The concentration of small proteoglycans, mainly decorin, decreased from 1.59
      (1.20-1.97) to 0.84 (0.24-1.41) micrograms/mg wet weight (P < .001), and the
      concentration of versican increased, but not significantly (P = .07). CONCLUSION:
      Concentrations of estrogen and progesterone receptors and insulin-like growth
      factor I messenger RNA were decreased significantly after spontaneous cervical
      ripening in comparison to levels before labor. These changes coincided with a
      tendency toward increased collagen solubility and a decline in concentration of
      small proteoglycans, which probably alters collagen organization, thus allowing
      for cervical softening and dilation. These observations suggest that gonadal
      steroids influence the final cervical remodeling during parturition, an influence
      perhaps mediated by insulin-like growth factor I.

PMID- 9277648
TI  - A prospective study of sleep, mood, and cognitive function in postpartum and
      nonpostpartum women.
AB  - OBJECTIVE: To compare the sleep patterns, mood states, and cognitive functioning
      of primiparous mothers during the first 3 weeks postpartum with those of a
      control group of nonpostpartum women and to assess the relationships among these
      variables. METHODS: For the first 3 weeks postpartum, 30 primiparous women and 28
      nonpostpartum mothers completed daily assessments of mood and recorded multiple
      aspects of sleep including time of retiring, occurrence and duration of sleep
      interruption, time of awakening, and morning alertness. Objective measures of
      memory, attention/concentration, and psychomotor performance were obtained on
      three occasions. RESULTS: Postpartum women reported more evening awakenings, more
      time awake after retiring, and more naps than controls, but overall sleep time
      was similar. New mothers experienced a higher level of dysphoric mood during the
      first week than nonpostpartum controls; however, controlling for the effect for
      "time awake" at night eliminated the significant effect for dysphoric mood. Few
      differences were observed on the multiple assessments of cognitive function;
      however, performances of new mothers on memory and psychomotor tasks were likely
      to be influenced by sleep loss. CONCLUSION: Women must make important adjustments
      in their sleep patterns during the postpartum period. In the study group, these
      adjustments were largely successful, particularly after the first week
      postpartum, in avoiding the negative consequences of sleep disturbances such as
      dysphoric mood and impaired cognitive function. Nevertheless, the significant
      associations between sleep indices and mood and objective measures of cognitive
      function point to the importance of encouraging appropriate amounts of sleep for
      recently delivered women.

PMID- 9277649
TI  - Factors influencing the prescription of hormone replacement therapy.
AB  - OBJECTIVE: To assess the effects of age, bone mineral density, risk of
      cardiovascular disease, and of breast cancer on the prevalence of hormone
      replacement therapy (HRT) prescriptions. METHODS: Seventeen charts of
      postmenopausal women were summarized. For each chart, we constructed 36 different
      cases by modifying the age (two levels), the bone mineral density (three levels),
      the cardiovascular risk (three levels), and the breast cancer risk (two levels).
      Twelve cases of these 612 files were sent to each Belgian gynecologist (n =
      1010). RESULTS: Overall, HRT was prescribed in 67% of the cases. It was
      prescribed in 54.6% of women who had a normal bone mass, 67.9% of women with a
      low bone mass, and 79.0% of those with osteoporosis (P < .001). The prescription
      rate was higher in younger women (mean +/- standard deviation 55 +/- 4 years)
      than in their peers who were 10 years older (79.3% versus 55.2%; p < .001). No
      significant variation was observed in relation to the cardiovascular risk profile
      or to breast cancer risk. CONCLUSION: Osteoporosis is associated with an
      increased rate and older age with a decreased rate of HRT prescription, whereas
      no difference is observed in association with cardiovascular or breast cancer
      risk.

PMID- 9277650
TI  - Menstrual cyclicity after metformin therapy in polycystic ovary syndrome.
AB  - OBJECTIVE: To assess the effect of insulin-lowering treatment on menstrual
      cyclicity in polycystic ovary syndrome (PCOS). METHODS: Forty oligoamenorrheic
      women with PCOS were recruited in a prospective clinical study to receive
      metformin for a minimum period of 6 months. Twenty-two women completed the study.
      Serum LH, FSH, free testosterone, and glucose and insulin response to oral
      glucose load were measured both before and after 8 weeks of metformin treatment.
      Menstrual cyclicity and serum progesterone levels at the midluteal phase were
      assessed at the 30th week of metformin treatment. RESULTS: Twenty-one of 22 women
      had restoration of menstrual cyclicity (95.7%). Four of these women (19%) became
      pregnant within the 6th and 7th months of treatment. All four of the pregnant
      women delivered, and the infants were healthy. Thirteen of 15 women who had
      regular menses demonstrated a serum progesterone level within the ovulatory range
      (3.1-28 ng/mL). Fasting (P < .001) and the integrated insulin response to the
      glucose load decreased (P < .001) after 8 weeks of metformin treatment. This was
      accompanied by significant decreases in serum LH (P < .001) and free testosterone
      (P < .001) levels and LH/FSH ratio (P < .001). There was a small but significant
      reduction in body mass index after 8 weeks of metformin treatment (P < .001).
      CONCLUSION: A 6-month course of metformin may improve menstrual cyclicity and
      fertility in women with the PCOS. Insulin-sensitizing agents provide a rational
      approach to the treatment of the metabolic and endocrine abnormalities in PCOS
      women.

PMID- 9277651
TI  - Transvaginal administration of progesterone.
AB  - OBJECTIVE: To examine the endometrial effects of three different doses of
      progesterone administered vaginally. METHODS: Forty women 25-41 years old
      deprived of ovarian function received estradiol (E2) for 28 days. From days 15 to
      27, a new mucus-like vaginal gel of progesterone was administered every other
      day, randomly, dosed at 45 mg (group A, n = 14), 90 mg (group B, n = 13), or 180
      mg (group C, n = 13). Plasma gonadotropins, estrone, E2, and progesterone were
      measured. An endometrial biopsy was performed on day 20 (n = 20) or 24 (n = 20)
      for endometrial dating and for estrogen and progesterone receptor determinations.
      RESULTS: Plasma estrogen levels were in the menstrual cycle range. Mean
      progesterone levels were lower in group A (2.4 +/- 0.2 ng/mL) than in group B
      (3.6 +/- 0.2 ng/mL) or C (3.4 +/- 0.4 ng/mL) (P < .005). Plasma FSH and LH
      decreased significantly during progesterone treatment. In all groups, we observed
      secretory transformation in the glands (day 20) and stroma (day 24) and the
      distribution of estrogen and progesterone receptors seen in normal menstrual
      cycles. CONCLUSION: Transvaginal administration of progesterone induced normal
      secretory transformation of the endometrium despite low plasma levels, suggesting
      a direct transit into the uterus or "first uterine pass effect."

PMID- 9277652
TI  - Estrogen and progesterone receptors in the uterosacral ligament.
AB  - OBJECTIVE: To evaluate steroid hormone receptor status in the uterosacral
      ligament, a structure that contributes to pelvic support. METHODS: A descriptive
      study was conducted by sampling the uterosacral ligaments from 25 consecutive
      women undergoing hysterectomy by the primary author for nonmalignant conditions.
      Using immunohistochemical staining techniques, uterosacral ligaments were
      assessed for the presence and location of estrogen and progesterone receptors.
      Positive and negative controls were used. Confirmation of the uterosacral
      ligament was performed histologically. RESULTS: Using commercially available
      monoclonal antibodies, estrogen and progesterone receptors were detected in the
      nuclei of smooth muscle cells of the uterosacral ligament in all patients,
      regardless of variations in age, race, menopausal status, parity, body mass
      index, and medications affecting serum steroid hormone levels. Hormone receptors
      were not found in the collagen, vascular, or neuronal components. CONCLUSION: The
      presence of estrogen and progesterone receptors in the uterosacral ligaments
      means that this structure may be a target for estrogen and progesterone. This
      finding might suggest a possible role for steroid hormones in pelvic support.

PMID- 9277653
TI  - Dissociation, somatization, substance abuse, and coping in women with chronic
      pelvic pain.
AB  - OBJECTIVE: To examine the relationships between histories of sexual or physical
      abuse and current reports of dissociation, somatization, substance abuse,
      adaptive coping, and maladaptive coping strategies among chronic pelvic pain
      patients. METHODS: Using a structured interview, we assessed sexual and physical
      abuse and somatization. The Dissociative Experiences Scale was used to assess
      dissociation, and an abbreviated version of the COPE scale was employed to assess
      adaptive and maladaptive coping strategies as well as substance abuse.
      Participants included 46 women with chronic pelvic pain. RESULTS: Women with self
      reported sexual or physical abuse histories were found to have significantly
      higher dissociation, somatization, and substance abuse scores than women without
      such a history. Significant positive correlations were found between reports of
      both dissociation and somatization with maladaptive coping strategies and among
      dissociation, somatization, and substance abuse. CONCLUSION: These results
      support the association between a positive abuse history and the high levels of
      dissociation, somatization, and substance abuse often noted in the chronic pelvic
      pain population. Findings suggest that such psychological variables are more
      likely to be associated with abuse than with the general medical condition. These
      psychological variables are conceptualized as maladaptive coping, which may be
      addressed as part of a biopsychosocial model of treatment for chronic pelvic pain
      patients.

PMID- 9277654
TI  - Open compared with laparoscopic approach to Burch colposuspension: a cost
      analysis.
AB  - OBJECTIVE: To compare postoperative course and hospital charges of an open versus
      laparoscopic approach to Burch colposuspension for the treatment of genuine
      stress urinary incontinence. METHODS: A retrospective chart review was performed
      to identify all patients undergoing open or laparoscopic Burch colposuspension by
      the same surgeon over a 2-year period. Patients undergoing additional surgical
      procedures at the time of colposuspension were excluded from the study. Twenty
      one patients underwent open Burch colposuspension and 17 patients underwent
      laparoscopic colposuspension. Demographic data including age, parity, height, and
      weight were collected for each group. Both groups also were compared with regard
      to operative time, operating room charges, estimated blood loss, intraoperative
      complications, change in postoperative hematocrit, time required to resume normal
      voiding, length of hospital stay, and total hospital charges. RESULTS: The
      laparoscopic colposuspension group had significantly longer operative times (110
      versus 66 minutes, P < .01) and increased operating room charges ($3479 versus
      $2138, P < .001). There was no statistical difference in estimated blood loss or
      change in postoperative hematocrit between the two groups. No major
      intraoperative complications occurred in either group. Mean length of hospital
      stay was 1.3 days for the laparoscopic group and 2.1 days for the open group (P <
      .005). However, total hospital charges for the laparoscopic group were
      significantly higher ($4960 versus $4079, P < .01). CONCLUSION: Laparoscopic
      colposuspension has been described as a minimally invasive, cost-effective
      technique for the surgical correction of stress urinary incontinence. Although
      the laparoscopic approach was found to be associated with a reduction in length
      of hospital stay, it had significantly higher total hospital charges than the
      traditional open approach because of expenses associated with increased operative
      time and use of laparoscopic equipment.

PMID- 9277655
TI  - A randomized comparison of gasless laparoscopy and CO2 pneumoperitoneum.
AB  - OBJECTIVE: To determine if the theoretic advantages of gasless laparoscopy are
      realized in direct comparison to laparoscopy with pneumoperitoneum. METHODS:
      Fifty-seven patients undergoing laparoscopic surgery chose to participate in this
      trial and were randomized after the induction of general anesthesia. Twenty-nine
      of the 57 patients were randomized to the pneumoperitoneum group. Of the 28
      patients in the gasless group, six were converted to pneumoperitoneum because of
      inadequate exposure. The adequacy of exposure and ease of surgery were assessed
      with a subjective score, and the times to exposure and for incision closure were
      recorded. Various anesthetic factors were measured. Patients completed an analog
      pain score in the recovery area and for the first 5 postoperative days. Analgesic
      and antiemetic use also was recorded, as was the number of days to return to
      normal activity. RESULTS: Times to achieve exposure and close incisions were
      longer, and exposure and ease of surgery were worse in the gasless group.
      Patients in the gasless group had lower diastolic blood pressure, minute
      ventilation, peak inspiratory pressures, and end tidal pCO2. There were no
      differences in body temperature, systolic blood pressure or heart rate,
      postoperative pain scores, analgesic or antiemetic use, or times to hospital
      discharge or return to activity between the groups. CONCLUSION: Performing
      laparoscopy using the Laparolift device compromised surgical exposure and thus
      increased technical difficulty. Patients realized no benefits from its use in
      terms of postoperative discomfort or return to activity. Eliminating the
      pneumoperitoneum allowed lower minute ventilation and peak inspiratory pressures,
      and end tidal pCO2 was lower. Although the concept of gasless laparoscopy holds
      appeal, the current prototype is not well-suited for infertility procedures.

PMID- 9277656
TI  - Effectiveness of the Papanicolaou smear and speculoscopy as compared with the
      Papanicolaou smear alone: a community-based clinical trial.
AB  - OBJECTIVE: To evaluate the screening effectiveness of speculoscopy, a magnified
      chemiluminescent visual examination combined with the Papanicolaou smear as
      compared with the Papanicolaou smear alone. METHODS: This was a prospective,
      practice-based study. The study participants were women aged 16-60 years who were
      regularly scheduled for Papanicolaou smears. All women were subject to a
      Papanicolaou smear and speculoscopy. Positive speculoscopy findings and/or
      Papanicolaou smear findings of a squamous intraepithelial lesion (SIL) were
      investigated further with colposcopy and biopsy. RESULTS: A total of 5692 women
      were evaluated, and 799 (14%) were positive by one or both screening tests. Of
      the 410 biopsy specimens that were obtained, 32 showed high-grade SIL, 191 low
      grade SIL, 145 reactive and reparative cells, and 42 were found to be within
      normal limits. The addition of speculoscopy to the routine Papanicolaou smear
      resulted in finding 11 of the 32 (34%) women with high-grade SIL and 154 of the
      191 (81%) women with low-grade SIL. CONCLUSION: Speculoscopy, when combined with
      the Papanicolaou smear as a screening test, yields a higher percentage of women
      with biopsy-confirmed cervical pathology than the use of the Papanicolaou smear
      as a sole screening test.

PMID- 9277657
TI  - Residual and recurrent disease after laser conization for cervical
      intraepithelial neoplasia.
AB  - OBJECTIVE: To assess the risk of residual and recurrent disease after carbon
      dioxide laser conization treatment for high-grade lesions of the cervix uteri,
      and thus to refine intervals for follow-up. METHODS: The study population
      comprised all women treated for cervical intraepithelial neoplasia grade II-III
      over a 10-year period (1983-1992). All women who resided within the county for
      the entire follow-up period were followed for residual or recurrent disease,
      verified histologically until the closure date of January 31, 1996. The
      cumulative incidence of recurrent disease was assessed by survival analyses, and
      logistic regression was used to predict clinical features at initial treatment
      that were associated with the risk of residual or recurrent disease. RESULTS:
      Only 19 of 1081 women (1.8%) were lost to follow-up. Residual disease was
      diagnosed in 20 (1.9%) study participants. The cumulative incidence of recurrent
      disease was extremely low, increasing nearly linearly with an annual incidence of
      three per 1000 woman-years observed. Involved resection margins were associated
      significantly with both residual disease (crude odds ratio [OR] 18.1; 95%
      confidence interval [CI] 5.2, 64.0) and recurrent disease (adjusted OR 3.0; 95%
      CI 1.2, 7.5) when compared with disease-free resection margins as reference.
      CONCLUSION: We recommend a differential follow-up interval depending upon the
      histologic evaluation of cone margins. If there is no residual disease, women who
      have free resection margins should return at a 3-year interval for follow-up.
      Women who have disease extended to the cone margins are recommended Papanicolaou
      smears at annual intervals through the fourth postoperative year before returning
      at a 3-year interval as practiced in the general screening program.

PMID- 9277658
TI  - Progestin treatment of atypical hyperplasia and well-differentiated carcinoma of
      the endometrium in women under age 40.
AB  - OBJECTIVE: To determine the efficacy of conservative management of atypical
      hyperplasia and well-differentiated carcinoma of the endometrium in women under
      age 40. METHODS: Pathology records were searched to identify women under age 40
      diagnosed with atypical hyperplasia or well-differentiated carcinoma of the
      endometrium between January 1990 and January 1996. All available biopsy,
      curettage, and hysterectomy specimens were reviewed. Follow-up was obtained from
      the patients' gynecologists. RESULTS: Sixty-seven records were identified.
      Atypical hyperplasia was found in 32 patients and well-differentiated carcinoma
      in 35 patients. Seven patients were excluded from analysis; four declined all
      treatment and follow-up, and three received no further treatment or tissue
      sampling from their physicians. Among 27 remaining patients with atypical
      hyperplasia, eight underwent hysterectomy, two were treated with ovulation
      induction, and 17 were treated with progestins, of whom 16 had regression of
      their lesions, and one had a persistent lesion. Among 33 women with well
      differentiated carcinoma, 19 underwent hysterectomy, one was treated with
      bromocriptine, one was treated with oral contraceptives, and 12 were treated with
      progestins, of whom nine had regression of their lesions and three had persistent
      lesions. The median length of treatment required for a regression was 9 months.
      At a mean follow-up of 40 months, all patients were alive and well without
      evidence of progressive disease. Twenty-five women attempted to become pregnant,
      and five delivered healthy, full-term infants. CONCLUSION: Treatment of atypical
      hyperplasia and well-differentiated carcinoma of the endometrium with progestins
      appears to be a safe alternative to hysterectomy in women under age 40.

PMID- 9277659
TI  - Value of preoperative CA 125 level in the management of uterine cancer and
      prediction of clinical outcome.
AB  - OBJECTIVE: To enhance cost-effective management of uterine cancer by predicting
      the likelihood of extrauterine disease and survival on the basis of preoperative
      parameters. METHODS: A retrospective review of preoperative CA 125 levels from
      210 women with endometrial carcinoma was performed. The relationship of
      preoperative CA 125 levels to various preoperative and postoperative
      histopathologic factors was investigated. RESULTS: Elevated CA 125 (greater than
      35 U/mL) correlated (P < .05) with higher stage, higher grade, increased depth of
      myometrial invasion, positive cytology, pelvic or para-aortic lymph node
      metastases, and reduced actuarial survival (P < .001). Multivariate analysis of
      preoperative factors showed that an elevated CA 125 level was the most important
      predictor for poor survival (P < .001). Moreover, a preoperative CA 125 level
      greater than 65 U/mL was the most significant predictor of extrauterine disease
      and carried a 6.5-fold higher risk (95% confidence interval 2.5, 17.1). A
      logistic model to predict extrauterine disease was developed. The model has a
      sensitivity of 62%, specificity of 91%, positive predictive value of 69%, and
      negative predictive value of 88%. CONCLUSION: A CA 125 level should be included
      as part of the preoperative workup for all patients with uterine cancer. Patients
      with a preoperative CA 125 level less than or equal to 20 U/mL should be
      considered as candidates for vaginal hysterectomy unless unfavorable histology or
      a high-grade (grade II or III) tumor is present. In our series, this approach
      would have eliminated 24% of the abdominal staging procedures, with a risk of
      less than 3% for extrauterine disease, while lowering treatment-related morbidity
      and cutting costs in the treatment of this common female cancer.

PMID- 9277660
TI  - Trends in squamous cell carcinoma of the vulva: the influence of vulvar
      intraepithelial neoplasia.
AB  - OBJECTIVE: To determine trends in the clinicopathology of vulvar squamous cell
      carcinoma over the past 2 decades, with particular reference to the possible
      effects of the increasing incidence of vulvar intraepithelial neoplasia (VIN)
      during this time. METHODS: Two cohorts of 56 and 57 women with squamous cell
      carcinoma of the vulva and separated by at least 2 decades were reviewed
      retrospectively. Pathologic specimens were analyzed concurrently. RESULTS: In the
      1965-1974 cohort, only one of 56 patients was younger than 50 years of age at the
      time of presentation, whereas in the 1990-1994 cohort, 12 of 57 (21%) were
      younger than 50 years of age (P = .001). Ten of 13 women younger than 50 years of
      age, compared with 13 of 100 of women 50 years of age or older, had warty or
      basaloid VIN associated with their invasive carcinoma (P < .001). Cigarette
      smoking and multiple lower genital tract neoplasia were both significantly more
      common in women younger than 50 years of age (P < .001). CONCLUSION: Over the
      past 2 decades, a subset of women younger than 50 years of age with squamous cell
      carcinoma of the vulva has emerged. Most of these carcinomas appear to arise in a
      field of warty or basaloid VIN. This suggests that the increasing incidence of
      VIN seen in young women during the past 2 decades is being reflected now in VIN
      associated squamous cell carcinoma of the vulva in younger women.

PMID- 9277661
TI  - Hysterectomy, oophorectomy in premenopause, and risk of breast cancer.
AB  - OBJECTIVE: To analyze the risk of breast cancer in women who underwent pelvic
      surgery in premenopause using data from two case-control studies conducted
      between 1983 and 1994 in six Italian centers. METHODS: Subjects were 5984 women
      with histologically confirmed breast cancer diagnosed within the year before
      interview who were admitted to the major teaching and general hospitals in the
      areas included in the studies. Controls were 5504 women who resided in the same
      geographic areas and were admitted for acute conditions to the same network of
      hospitals in which cases had been identified. Women were not included if they had
      been admitted for gynecologic, hormonal, or neoplastic disease. RESULTS: A total
      of 719 cases (12%) and 801 controls (15%) underwent pelvic surgery before
      menopause. The risk of breast cancer was reduced in women who underwent bilateral
      oophorectomy with hysterectomy (odds ratio [OR] adjusted for age, calendar year
      at interview, study, and center, 0.8, 95% confidence interval [CI] 0.7, 0.9) and
      hysterectomy alone (OR 0.7, 95% CI 0.6, 0.8). The protection tended to increase
      with time since surgery, but no relationship emerged when age at menopause was
      included in the analysis. No clear relationship emerged between time since
      unilateral oophorectomy with or without hysterectomy or since hysterectomy alone
      and breast cancer risk. CONCLUSION: The risk of breast cancer is lower in women
      who undergo bilateral oophorectomy before menopause, and the protection increases
      with time from surgery.

PMID- 9277662
TI  - Prenatal screening for toxoplasmosis.
AB  - OBJECTIVE: To evaluate the merits of screening for toxoplasmosis in all pregnant
      women. METHODS: We used decision analysis to compare three strategies for the
      antepartum management of congenital toxoplasmosis: 1) no testing for congenital
      toxoplasmosis; 2) current practice, which is to perform targeted screening in
      cases of incidental abnormalities noted on ultrasound; and 3) universal serologic
      screening of pregnant women followed by amniocentesis to diagnose fetal infection
      in cases of maternal seroconversion. For each of the three strategies, we
      considered the two available treatment options: intrauterine antiparasitic
      treatment or pregnancy termination. RESULTS: Universal screening reduced the
      total number of cases of congenital toxoplasmosis compared with no testing or
      targeted screening. However, compared with no testing, universal screening with
      medical treatment resulted in 18.5 additional pregnancy losses for each case of
      toxoplasmosis avoided. If infected pregnancies underwent termination, universal
      screening resulted in 12.1 additional pregnancy losses for each case avoided.
      CONCLUSION: Maternal screening reduces the number of cases of disease, but at a
      substantial clinical cost. The rarity of the disease and limitations in diagnosis
      and therapy limit the effectiveness of screening strategies. The risks associated
      with amniocentesis are particularly important. Universal maternal screening for
      congenital toxoplasmosis should not be performed.

PMID- 9277663
TI  - Maternal serum interleukin-6 during pregnancy and during term and preterm labor.
AB  - OBJECTIVE: To determine the normal concentrations of maternal serum interleukin-6
      during the second and third trimesters of pregnancy and the different stages of
      term and preterm labor, and to examine the clinical usefulness of measuring this
      cytokine in the serum of women in preterm labor to diagnose asymptomatic
      intrauterine infections. METHODS: Maternal serum interleukin-6 concentrations
      were measured cross-sectionally in 315 gravidas in their second and third
      trimesters and during term and preterm labor. Placentas from women who delivered
      preterm were examined for histologic chorioamnionitis. RESULTS: At term, women in
      labor had significantly elevated median maternal serum interleukin-6
      concentrations compared with those at term not in labor (4.7 pg/mL versus 2.2
      pg/mL, P < .001). Women admitted in preterm labor who delivered had significantly
      higher median interleukin-6 concentrations than did those in preterm labor who
      responded to tocolysis (9.3 pg/mL versus 1.9 pg/mL, P < .001). Women in preterm
      labor who delivered preterm with evidence of chorioamnionitis had significantly
      higher serum concentrations of interleukin-6 than did those in preterm labor who
      delivered in the absence of chorioamnionitis (15.9 pg/mL versus 4.6 pg/mL, P =
      .006). CONCLUSION: Compared with antepartum gravidas, those in term or preterm
      labor had significantly higher concentrations of maternal serum interleukin-6
      concentrations; extremely elevated levels were found in patients whose preterm
      labor was associated with intrauterine infection.

PMID- 9277664
TI  - The Leicester Endometrial Needle Sampler: a novel device for endometrial and
      myometrial junctional zone biopsy.
AB  - A 48-cm-long, fine (16 gauge) needle was purpose-built to our design for full
      thickness endometrial sampling. It is driven by a high-speed cutting device that
      has a two-step action-loaded spring, and is adjusted to a penetration depth of 16
      mm. Pain and tolerance were assessed on a visual analogue scale. The histologic
      diagnosis obtained by this device, the Leicester Endometrial Needle Sampler, was
      compared with that of Pipelle endometrial sampling in 40 patients at the end of
      panoramic hysteroscopy under local anesthesia. The patients' mean age was 51
      years (range 39-60) and the mean parity was 2.4 (range 0-6). The mean (+/
      standard deviation) pain score was 3.7 +/- 2.2 and the mean tolerability score
      was 4.4 +/- 3.6. The technique helped to procure a full-thickness endometrial
      biopsy in all cases, from targeted areas including the myometrial junctional
      zone, with 100% efficiency.

PMID- 9277665
TI  - Research design and methods of quantitative synthesis of medical evidence.
AB  - OBJECTIVE: To review the scientific principles, strengths, and limitations of
      research designs and methods of quantitative synthesis of medical evidence. DATA
      SOURCES: We used MEDLINE to perform a systematic search for literature using the
      keywords research design, epidemiology, and biometry. Journals searched included
      six major journals in obstetrics and gynecology and three in general medicine.
      These sources were supplemented with texts and reviews from the general medical
      literature. METHODS OF STUDY SELECTION: We reviewed the publications identified
      by our search and evaluated critically the relevant reports. We summarized
      objectives and scientific guidelines for the common research methodologies and
      outlined their advantages and disadvantages. TABULATION, INTEGRATION, AND
      RESULTS: The standard of clinical research design is the randomized controlled
      trial (RCT), which, if performed with sufficient methodologic rigor, is least
      likely to have serious biases. Cohort, case-control, and cross-sectional studies
      are common observational studies used in reproductive health; such observational
      studies are more susceptible to biases that can distort the researcher's results
      and conclusions. Descriptive studies such as case series and case reports are
      often interesting as clinical vignettes but have limited scientific merit.
      Methods for quantitative synthesis of medical evidence, including meta-analysis,
      decision analysis, and cost-effectiveness analysis are being used with increased
      frequency in the reproductive health literature to summarize medical evidence.
      CONCLUSION: Various research methods have their own inherent advantages and
      disadvantages. An understanding of the scientific principles of these methods
      will enable the clinician to evaluate medical evidence critically.

PMID- 9277666
TI  - Birth weight as a predictor of brachial plexus injury.

PMID- 9277667
TI  - Birth weight as a predictor of brachial plexus injury.

PMID- 9277668
TI  - The association between hypertensive disorders of pregnancy and abnormal second
      trimester maternal serum levels of hCG and alpha-fetoprotein.

PMID- 9277669
TI  - Pubic bone suburethral stabilization sling for recurrent urinary incontinence.

PMID- 9277670
TI  - [Acute on chronic renal failure].

PMID- 9277671
TI  - [Acute renal failure].

PMID- 9277672
TI  - [Acute tubular necrosis].

PMID- 9277673
TI  - [Renal osteomalacia].

PMID- 9277674
TI  - [Renal dwarfism].

PMID- 9277676
TI  - [Renal infantilism].

PMID- 9277675
TI  - [Renal retinopathy].

PMID- 9277677
TI  - [Renal papillary necrosis].

PMID- 9277678
TI  - [Renal cortical necrosis].

PMID- 9277679
TI  - [Uremic syndrome].

PMID- 9277680
TI  - [Uremic arthritis].

PMID- 9277681
TI  - [Uremic pleuritis].

PMID- 9277682
TI  - [Gastrointestinal complications of uremic syndrome].

PMID- 9277683
TI  - [Uremic cardiomyopathy].

PMID- 9277684
TI  - [Uremic pericarditis].

PMID- 9277685
TI  - [Uremic neuropathy].

PMID- 9277686
TI  - [Uremic encephalopathy, uremic coma].

PMID- 9277687
TI  - [Uremic lung].

PMID- 9277688
TI  - [Uremic myopathy].

PMID- 9277689
TI  - [Uremic dyslipoproteinemia].

PMID- 9277690
TI  - [Chronic renal failure].

PMID- 9277691
TI  - [Alport syndrome].

PMID- 9277693
TI  - [IgA nephropathy].

PMID- 9277692
TI  - [Fibrillary glomerulonephritis, immunotactoid glomerulopathy].

PMID- 9277694
TI  - [MRSA-related glomerulonephritis].

PMID- 9277695
TI  - [Necrotizing glomerulonephritis (necrotizing glomerulitis)].

PMID- 9277696
TI  - [Extracapillary proliferative glomerulonephritis].

PMID- 9277697
TI  - [Acute postinfectious glomerulonephritis].

PMID- 9277698
TI  - [Endocapillary proliferative glomerulonephritis].

PMID- 9277699
TI  - [Acute glomerulonephritis].

PMID- 9277700
TI  - [Acute renal failure in glomerulonephritis and nephrotic syndrome].

PMID- 9277701
TI  - [Rapidly progressive glomerulonephritis (RPGN)].

PMID- 9277702
TI  - [Primary and secondary glomerular diseases].

PMID- 9277703
TI  - [Sclerosing glomerulonephritis].

PMID- 9277704
TI  - [Antitubular basement membrane antibody nephritis].

PMID- 9277705
TI  - [Collagenofibrotic glomerulonephropathy, collagen deposition disease].

PMID- 9277706
TI  - [Glomerular capillary endotheliosis].

PMID- 9277707
TI  - [Glomerulosclerosis].

PMID- 9277708
TI  - [Glomerular fibrosis].

PMID- 9277709
TI  - [Glomerulocystic kidney].

PMID- 9277710
TI  - [Renal diseases with glomerular hypertrophy].

PMID- 9277711
TI  - [Glomerular lipidosis].

PMID- 9277712
TI  - [Superantigen-related nephritis(SARN)].

PMID- 9277713
TI  - [Congenital glomerulosclerosis].

PMID- 9277714
TI  - [Congenital nephrotic syndrome].

PMID- 9277715
TI  - [Focal necrotizing glomerulonephritis].

PMID- 9277716
TI  - [Focal glomerulosclerosis].

PMID- 9277717
TI  - [Granulomatous glomerulonephritis].

PMID- 9277718
TI  - [Nephrotic syndrome (primary, secondary)].

PMID- 9277719
TI  - [Minimal change glomerulonephritis].

PMID- 9277720
TI  - [Lobular glomerulonephritis].

PMID- 9277721
TI  - [Membranous nephropathy].

PMID- 9277722
TI  - [Membranoproliferative glomerulonephritis (type I, type III)].

PMID- 9277723
TI  - [Membranoproliferative glomerulonephritis type II (dense deposit disease)].

PMID- 9277724
TI  - [Chronic glomerulonephritis (latent type, advanced type)].

PMID- 9277725
TI  - [Mesangial proliferative glomerulonephritis].

PMID- 9277726
TI  - [Lipoprotein glomerulopathy].

PMID- 9277727
TI  - [Benign familial hematuria (thin basement membrane disease)].

PMID- 9277728
TI  - [Atrophic pyelonephritis].

PMID- 9277729
TI  - [Xanthogranulomatous pyelonephritis].

PMID- 9277730
TI  - [Emphysematous pyelonephritis].

PMID- 9277731
TI  - [Interstitial nephritis associated with neoplasms].

PMID- 9277732
TI  - [Pyelonephritis].

PMID- 9277733
TI  - [Pyelitis glandularis].

PMID- 9277735
TI  - [Idiopathic tubulointerstitial nephritis (acute, chronic)].

PMID- 9277734
TI  - [Specific infections of the kidney].

PMID- 9277736
TI  - [Granulomatous interstitial nephritis].

PMID- 9277737
TI  - [Tubulo-interstitial nephropathy; TIN].

PMID- 9277738
TI  - [Acute interstitial nephritis with bone marrow granulomas and uveitis].

PMID- 9277739
TI  - [Obstructive pyelonephritis].

PMID- 9277740
TI  - [Reflux nephropathy in vesico-ureteral reflux (VUR)].

PMID- 9277741
TI  - [Tubulointerstitial nephritis induced by chronic bacterial infection].

PMID- 9277742
TI  - [Tubulo-interstitial nephritis associated with abnormal immune system].

PMID- 9277743
TI  - [Immune complex mediated tubulo-interstitial nephritis].

PMID- 9277744
TI  - [Nutcracker phenomenon].

PMID- 9277745
TI  - [Patchy renal vasoconstriction].

PMID- 9277746
TI  - [Multiple renal arteries].

PMID- 9277747
TI  - [Renal necrotizing vasculitis].

PMID- 9277748
TI  - [Nephrosclerosis (benign, malignant)].

PMID- 9277749
TI  - [Renal infarction, infarcted kidney].

PMID- 9277750
TI  - [Renal vein thrombosis].

PMID- 9277751
TI  - [Renal thrombotic microangiopathy].

PMID- 9277752
TI  - [Renal arteriovenous fistula].

PMID- 9277753
TI  - [Renal arteritis].

PMID- 9277754
TI  - [Renal artery stenosis].

PMID- 9277755
TI  - [Renal arterial thrombosis, renal arterial embolism, renal artery occlusion].

PMID- 9277756
TI  - [Renovascular fibromuscular hyperplasia (dysplasia)].

PMID- 9277757
TI  - [Renal artery aneurysm].

PMID- 9277758
TI  - [Jeune syndrome].

PMID- 9277759
TI  - [Ectopic kidney, renal ectopy].

PMID- 9277760
TI  - [Malrotated kidney].

PMID- 9277761
TI  - [Supernumerary kidney].

PMID- 9277762
TI  - [Megacalycosis].

PMID- 9277763
TI  - [Renal agenesis, renal dysplasia, renal aplasia, renal hypoplasia,
      oligomeganephronia].

PMID- 9277764
TI  - [Fused kidney--anomalies of renal fusion (lobulated kidney)].

PMID- 9277765
TI  - [Duplicated renal pelvis, triplicated renal pelvis, bifid pelvis].

PMID- 9277766
TI  - [Extrarenal calyces: extrarenal collecting system].

PMID- 9277767
TI  - [Renal retinal dysplasia].

PMID- 9277768
TI  - [Hydrocalycosis].

PMID- 9277769
TI  - [Congenital hydronephrosis].

PMID- 9277770
TI  - [Unipapillary kidney, multipapillary kidney].

PMID- 9277771
TI  - [Segmental renal hypoplasia (Ask-Upmark kidney)].

PMID- 9277772
TI  - [Juvenile nephronophthisis-medullary cystic disease (JN-MCD) complex].

PMID- 9277773
TI  - [Meckel syndrome].

PMID- 9277774
TI  - [Miranda syndrome].

PMID- 9277775
TI  - [Medullary sponge kidney].

PMID- 9277776
TI  - [Acquired renal cystic disease].

PMID- 9277777
TI  - [Hemorrhagic renal cyst].

PMID- 9277778
TI  - [Polycystic kidney disease].

PMID- 9277779
TI  - [Perirenal pseudocyst].

PMID- 9277780
TI  - [Simple renal cysts, localized cystic disease, and multilocular renal cysts].

PMID- 9277781
TI  - [Calyceal diverticulum].

PMID- 9277782
TI  - [Pericalyceal cyst, parapelvic cyst].

PMID- 9277783
TI  - [Pericalyceal lymphangiectasia].

PMID- 9277784
TI  - [Renal dysplasia].

PMID- 9277785
TI  - [Renal cystic disease].

PMID- 9277786
TI  - [Cystadenocarcinoma of renal pelvic origin in a supernumerary kidney].

PMID- 9277787
TI  - [Chromophobe renal cell carcinoma].

PMID- 9277788
TI  - [Renal tumor with acquired cystic disease of the kidney].

PMID- 9277789
TI  - [Clear cell sarcoma of the kidney].

PMID- 9277790
TI  - [Renal pelvic tumor (transitional cell carcinoma, squamous cell carcinoma,
      adenocarcinoma, etc.)].

PMID- 9277791
TI  - [Renal oncocytoma].

PMID- 9277792
TI  - [Nephroblastoma].

PMID- 9277793
TI  - [Renal pseudotumor].

PMID- 9277794
TI  - [Renal angiomyolipoma].

PMID- 9277795
TI  - [Renal cell carcinoma].

PMID- 9277796
TI  - [Liposarcoma, lipoma and lipomatosis of the kidney].

PMID- 9277797
TI  - [Benign and malignant renal tumors].

PMID- 9277799
TI  - [Renal adenoma].

PMID- 9277798
TI  - [Renomedullary interstitial cell tumor, renal medullary fibroma].

PMID- 9277800
TI  - [Renal leiomyoma and renal leiomyosarcoma].

PMID- 9277801
TI  - [Congenital mesoblastic nephroma].

PMID- 9277802
TI  - [Multilocular cystic nephroma, multilocular renal cyst].

PMID- 9277803
TI  - [Mesonephric tumor, mesonephric carcinoma].

PMID- 9277804
TI  - [Juxtaglomerular cell tumor].

PMID- 9277806
TI  - [Nephropathy induced by stimulants and narcotics (heroin, amphetamine, etc)].

PMID- 9277807
TI  - [Gold nephropathy].

PMID- 9277805
TI  - [D-penicillamine nephropathy].

PMID- 9277808
TI  - [Renal complications of anti-hypertensive drugs].

PMID- 9277809
TI  - [Nephropathy induced by anticonvulsants].

PMID- 9277810
TI  - [Nephrotoxicity of antineoplastic agents (antibiotics)].

PMID- 9277811
TI  - [Nephrotoxicity of antineoplastic drugs].

PMID- 9277812
TI  - [Antimicrobial nephrotoxicity].

PMID- 9277813
TI  - [Sulfonamide nephropathy].

PMID- 9277814
TI  - [Cyclosporine nephrotoxicity (chronic arteriolopathy, glomerulopathy)].

PMID- 9277815
TI  - [Ciprofloxacin nephropathy, acyclovir nephropathy].

PMID- 9277816
TI  - [Nephropathy by food poisoning].

PMID- 9277818
TI  - [Toxic nephropathy].

PMID- 9277817
TI  - [Contrast nephropathy].

PMID- 9277819
TI  - [Renal dysfunction caused by animal poisons (snake venoms, bite and punctured
      poisoning)].

PMID- 9277820
TI  - [Nephrotoxicity of non steroidal anti-inflammatory drugs (NSAID)].

PMID- 9277821
TI  - [Nephropathy induced by non-drug chemical agents].

PMID- 9277822
TI  - [Renal failure caused by the ingestion of poisonous mushrooms].

PMID- 9277823
TI  - [Lithium-induced renal disease].

PMID- 9277824
TI  - [Diuretic associated renal diseases].

PMID- 9277825
TI  - [Bartter's syndrome, Gitelman's syndrome].

PMID- 9277826
TI  - [Carbonic anhydrase II deficiency].

PMID- 9277827
TI  - [Fanconi syndrome].

PMID- 9277828
TI  - [Liddle syndrome].

PMID- 9277829
TI  - [Lowe syndrome].

PMID- 9277830
TI  - [Luder-Sheldon syndrome].

PMID- 9277832
TI  - [Type II (proximal) renal tubular acidosis].

PMID- 9277831
TI  - [Type I renal tubular acidosis (type I RTA)].

PMID- 9277833
TI  - [Type III renal tubular acidosis].

PMID- 9277834
TI  - [Type IV renal tubular acidosis].

PMID- 9277835
TI  - [Renal tubule transport defect of amino acids].

PMID- 9277837
TI  - [Pseudo-Bartter syndrome].

PMID- 9277836
TI  - [Potassium-losing nephropathy].

PMID- 9277838
TI  - [Pseudohypoaldosteronism (type I)].

PMID- 9277839
TI  - [Pseudohypoaldosteronism (type II)].

PMID- 9277841
TI  - [Renal hypouricemia (idiopathic, secondary)].

PMID- 9277840
TI  - [Primary hypophosphatemic rickets].

PMID- 9277842
TI  - [Renal glucosuria].

PMID- 9277843
TI  - [Nephrogenic diabetes insipidus].

PMID- 9277844
TI  - [Idiopathic tubular proteinuria (Dent's disease)].

PMID- 9277845
TI  - [Sodium-losing nephropathy].

PMID- 9277846
TI  - [Pleuroperitoneal communication].

PMID- 9277847
TI  - [CAPD peritonitis, CAPD sclerosing peritonitis].

PMID- 9277848
TI  - [Restless legs syndrome].

PMID- 9277849
TI  - [Amyloid renal stone].

PMID- 9277850
TI  - [Metastatic calcification in dialysis patients].

PMID- 9277851
TI  - [Rhabdomyolysis, muscle disorder].

PMID- 9277852
TI  - [Ischemic heart disease in chronic dialysis patients].

PMID- 9277853
TI  - [Burning feet syndrome].

PMID- 9277854
TI  - [Carpal tunnel syndrome].

PMID- 9277855
TI  - [Upper gastrointestinal complication in renal failure].

PMID- 9277856
TI  - [First dialysis syndrome, first-use syndrome].

PMID- 9277857
TI  - [Pericarditis in uremia].

PMID- 9277858
TI  - [Renal cell carcinoma in dialysis patients].

PMID- 9277859
TI  - [Renal osteodystrophy].

PMID- 9277860
TI  - [Anemia of end-stage renal disease (ESRD)].

PMID- 9277861
TI  - [Cardiac failure].

PMID- 9277862
TI  - [Spondylolisthesis in long-term hemodialysis patients].

PMID- 9277863
TI  - [Dialysis related amyloidosis].

PMID- 9277864
TI  - [Dialysis arthropathy].

PMID- 9277865
TI  - [Infectious disease in hemodialysis patients].

PMID- 9277866
TI  - [Hemodialyzed fundus].

PMID- 9277867
TI  - [Dialysis shoulder].

PMID- 9277868
TI  - [Hypertension in dialysis patients].

PMID- 9277869
TI  - [Disdialysis syndrome].

PMID- 9277871
TI  - [Dialysis-induced hypotension].

PMID- 9277870
TI  - [Uremic cardiomyopathy].

PMID- 9277872
TI  - [Dialysis encephalopathy and dialysis dementia].

PMID- 9277874
TI  - [Endocrinological derangement in uremia].

PMID- 9277875
TI  - [Cerebrovascular disease in dialysis patients].

PMID- 9277876
TI  - [Uremic pruritus].

PMID- 9277877
TI  - [Disequilibrium syndrome].

PMID- 9277878
TI  - [Hyperparathyroidism, hypoparathyroidism].

PMID- 9277873
TI  - [Complications of internal arteriovenous fistula in hemodialysis].

PMID- 9277879
TI  - [Arrhythmia in uremia].

PMID- 9277880
TI  - [Hemochromatosis, hemosiderosis].

PMID- 9277881
TI  - [Adynamic bone disease].

PMID- 9277882
TI  - [Immune deficiency].

PMID- 9277883
TI  - [Bardet-Biedl syndrome].

PMID- 9277884
TI  - [Cushing's syndrome].

PMID- 9277885
TI  - [Renal impairment in familial hyperaldosteronism].

PMID- 9277887
TI  - [Pseudohypoparathyroidism].

PMID- 9277888
TI  - [Primary aldosteronism (Conn's syndrome)].

PMID- 9277886
TI  - [Pheochromocytoma].

PMID- 9277889
TI  - [Primary hyperparathyroidism].

PMID- 9277890
TI  - [Thyroid antigen-antibody nephritis].

PMID- 9277891
TI  - [Multiple endocrine neoplasia and renal disorder].

PMID- 9277892
TI  - [Hyporeninemic hypoaldosteronism].

PMID- 9277893
TI  - [Water and electrolyte metabolism in adrenal insufficiency].

PMID- 9277894
TI  - [Hypercalcemic nephropathy].

PMID- 9277895
TI  - [Hyperoxaluria].

PMID- 9277897
TI  - [Diabetic nephropathy complicated with glomerulonephritis].

PMID- 9277896
TI  - [Renal function in hyperuricemia].

PMID- 9277898
TI  - [Hypokalemic nephropathy].

PMID- 9277899
TI  - [Diabetic capsular drop, fibrin cap, and the other exudative lesions].

PMID- 9277900
TI  - [Diabetic glomerulosclerosis (diffuse lesion, nodular lesion)].

PMID- 9277901
TI  - [Diabetic nephropathy, early diabetic nephropathy].

PMID- 9277903
TI  - [Acute renal failure in patients with diabetes mellitus].

PMID- 9277902
TI  - [Tubulointerstitial injury in diabetes mellitus (including Armanni-Ebstein
      lesion)].

PMID- 9277905
TI  - [APRT deficiency].

PMID- 9277904
TI  - [Milk-alkali syndrome].

PMID- 9277906
TI  - [Glutaric acidemia type II].

PMID- 9277907
TI  - [LCAT deficiency and renal lesion].

PMID- 9277909
TI  - [Wilson's disease].

PMID- 9277908
TI  - [Renal insufficiency caused by Lesch-Nyhan syndrome].

PMID- 9277910
TI  - [Metabolic disorders of amino acids].

PMID- 9277911
TI  - [Orotic aciduria].

PMID- 9277912
TI  - [Renal damage with familial hyper alpha-lipoproteinemia].

PMID- 9277913
TI  - [Familial juvenile gouty nephropathy].

PMID- 9277915
TI  - [Muscle glycogenosis].

PMID- 9277914
TI  - [Xanthinuria].

PMID- 9277916
TI  - [Glycogen storage disease].

PMID- 9277917
TI  - [Peroxisomal disorders (Zellweger syndrome)].

PMID- 9277918
TI  - [Lysosomal storage disease].

PMID- 9277919
TI  - [Renal involvement in Castleman's disease].

PMID- 9277920
TI  - [POEMS syndrome (Crow-Fukase syndrome)].

PMID- 9277922
TI  - [Malignant lymphoma].

PMID- 9277921
TI  - [von Willebrand disease--including related renal diseases].

PMID- 9277923
TI  - [Sickle cell nephropathy].

PMID- 9277924
TI  - [Macrothrombocytopenia].

PMID- 9277925
TI  - [Cryoglobulinemia].

PMID- 9277926
TI  - [Light chain deposition disease (LCDD), light and heavy chain deposition disease
      (LHCDD)].

PMID- 9277927
TI  - [Thrombotic thrombocytopenic purpura].

PMID- 9277928
TI  - [Renal damage in Waldenstrom's macroglobulinemia].

PMID- 9277929
TI  - [Renal involvement in primary immunodeficiency].

PMID- 9277930
TI  - [Microangiopathic hemolytic anemia].

PMID- 9277931
TI  - [Adult T-cell leukemia].

PMID- 9277932
TI  - [Hereditary protein S deficiency].

PMID- 9277933
TI  - [Multiple myeloma].

PMID- 9277934
TI  - [Nephropathy associated with idiopathic plasmacytic lymphadenopathy with
      polyclonal hyperimmunoglobulinemia (IPL)].

PMID- 9277935
TI  - [Disseminated intravascular coagulation].

PMID- 9277936
TI  - [Leukemia and renal disease].

PMID- 9277937
TI  - [Renal disorders in paroxysmal nocturnal hemoglobinuria].

PMID- 9277938
TI  - [Haemolytic uremic syndrome].

PMID- 9277939
TI  - [Benign monoclonal gammopathy].

PMID- 9277940
TI  - [ANCA-positive necrotizing glomerulonephritis].

PMID- 9277941
TI  - [Behcet's disease and renal diseases].

PMID- 9277942
TI  - [Churg-Strauss syndrome].

PMID- 9277943
TI  - [CREST syndrome].

PMID- 9277944
TI  - [Reiter's syndrome].

PMID- 9277945
TI  - [Sjogren's syndrome].

PMID- 9277946
TI  - [Still's disease].

PMID- 9277947
TI  - [Wegener's granulomatosis].

PMID- 9277948
TI  - [Allergic vasculitis, hypersensitivity angiitis].

PMID- 9277949
TI  - [Scleroderma, scleroderma kidney, scleroderma renal crisis].

PMID- 9277950
TI  - [Polyarteritis nodosa].

PMID- 9277951
TI  - [Microscopic polyarteritis nodosa (microscopic polyangiitis; MPA)].

PMID- 9277952
TI  - [Antiphospholipid antibody syndrome].

PMID- 9277953
TI  - [Mixed connective tissue disease].

PMID- 9277954
TI  - [Henoch-Schonlein purpura nephritis].

PMID- 9277955
TI  - [Systemic lupus erythematosus].

PMID- 9277956
TI  - [Aortitis syndrome].

PMID- 9277957
TI  - [Polymyositis-dermatomyositis].

PMID- 9277958
TI  - [Overlap syndrome].

PMID- 9277959
TI  - [Nephropathy associated with rheumatoid arthritis].

PMID- 9277960
TI  - [Renal involvement in hepatitis A].

PMID- 9277961
TI  - [Hepatitis B virus associated glomerulonephritis].

PMID- 9277962
TI  - [Hepatitis C virus associated glomerulonephritis].

PMID- 9277964
TI  - [Cirrhosis of the liver].

PMID- 9277965
TI  - [Hepatic IgA nephropathy].

PMID- 9277963
TI  - [Renal involvement in a patient with ulcerative colitis].

PMID- 9277966
TI  - [Primary biliary cirrhosis and renal disease].

PMID- 9277967
TI  - [Autoimmune hepatitis].

PMID- 9277968
TI  - [Renal disturbance in biliary disease and obstructive jaundice].

PMID- 9277969
TI  - [Kidney in chronic active hepatitis].

PMID- 9277970
TI  - [Acute heart failure and shock].

PMID- 9277971
TI  - [Endocarditis].

PMID- 9277972
TI  - [Heart failure].

PMID- 9277973
TI  - [Alstrom syndrome].

PMID- 9277974
TI  - [Kabuki make-up syndrome].

PMID- 9277976
TI  - [Prune belly syndrome].

PMID- 9277975
TI  - [Prader-Willi syndrome].

PMID- 9277977
TI  - [Senior-Loken syndrome].

PMID- 9277978
TI  - [Epstein syndrome].

PMID- 9277979
TI  - [HIV associated nephropathy].

PMID- 9277980
TI  - [Amyloidosis].

PMID- 9277982
TI  - [Virus-related renal diseases].

PMID- 9277983
TI  - [Rhabdomyolysis].

PMID- 9277981
TI  - [Glomerulopathy in renal allografts: transplant glomerulonephritis and IgA
      glomerulopathy].

PMID- 9277984
TI  - [Pseudoaldosteronism].

PMID- 9277985
TI  - [Serum sickness].

PMID- 9277986
TI  - [Eosinophilic lymphfolliculoid granuloma (Kimura's disease)].

PMID- 9277987
TI  - [Nephropathy associated with solid tumor].

PMID- 9277988
TI  - [Bone marrow transplantation related hemolytic uremic syndrome, bone marrow
      transplantation related thrombotic microangiopathy].

PMID- 9277989
TI  - [Crush syndrome].

PMID- 9277990
TI  - [Renal involvement of sarcoidosis].

PMID- 9277991
TI  - [Acute renal failure associated with pregnancy and postpartum acute renal
      failure].

PMID- 9277992
TI  - [Myasthenia gravis].

PMID- 9277993
TI  - [Acute renal failure after surgery].

PMID- 9277994
TI  - [Nail patella syndrome].

PMID- 9277995
TI  - [Acute renal failure in the patients with multiple organ failure].

PMID- 9277996
TI  - [Acute pyelonephritis in pregnancy].

PMID- 9277997
TI  - [Preeclampsia].

PMID- 9277998
TI  - [Foam cell syndrome].

PMID- 9277999
TI  - [Phacomatosis].

PMID- 9278000
TI  - [Epidemic hemorrhagic fever].

PMID- 9278001
TI  - [Bullous pemphigoid].

PMID- 9278002
TI  - [Denys-Drash syndrome].

PMID- 9278003
TI  - [Ormond's syndrome (retroperitoneal fibrosis)].

PMID- 9278004
TI  - [Ostertag syndrome].

PMID- 9278005
TI  - [Post-obstruction syndrome].

PMID- 9278006
TI  - [TUR syndrome].

PMID- 9278007
TI  - [Albuminuric retinopathy].

PMID- 9278008
TI  - [Familial idiopathic low molecular weight proteinuria, asymptomatic low molecular
      weight proteinuria].

PMID- 9278009
TI  - [Spontaneous peripelvic extravasation].

PMID- 9278010
TI  - [Shunt nephritis].

PMID- 9278012
TI  - [Nephrolithiasis].

PMID- 9278011
TI  - [Renal parasitism].

PMID- 9278013
TI  - [Renal protozoiasis].

PMID- 9278014
TI  - [Perinephritis--perinephric abscess, perirenal abscess].

PMID- 9278015
TI  - [Perirenal hematoma].

PMID- 9278016
TI  - [Renal mycoses].

PMID- 9278017
TI  - [Renal polycythemia, Forssell syndrome].

PMID- 9278018
TI  - [Nephrocalcinosis].

PMID- 9278019
TI  - [Trauma of the urinary tract and crush syndrome].

PMID- 9278020
TI  - [Renal abscess].

PMID- 9278022
TI  - [Postural proteinuria (orthostatic proteinuria)].

PMID- 9278021
TI  - [Spirochetosis].

PMID- 9278023
TI  - [Idiopathic renal hematuria].

PMID- 9278024
TI  - [Heat nephropathy].

PMID- 9278025
TI  - [Pyonephrosis--pyohydronephrosis].

PMID- 9278026
TI  - [Pyeloureteritis cystica].

PMID- 9278027
TI  - [Obstructive nephropathy].

PMID- 9278028
TI  - [Radiation nephritis].

PMID- 9278029
TI  - [Infection of mycoplasma].

PMID- 9278030
TI  - [Floating kidney (renal ptosis, nephroptosis, movable kidney, wanderniere)].

PMID- 9278031
TI  - [Rickettsiosis].

PMID- 9278032
TI  - [Goodpasture syndrome, pseudo Goodpasture syndrome].

PMID- 9278033
TI  - [Acute infectious tubulointerstitial nephritis].

PMID- 9278034
TI  - [Balkan nephropathy, Balkan endemic nephropathy].

PMID- 9278035
TI  - Karolinska Institute disowns work of cancer researcher.

PMID- 9278037
TI  - Peer review is a two-way process.

PMID- 9278036
TI  - Peer review is a two-way process.

PMID- 9278038
TI  - Biological hydrostats. Wrapping the armadillo's penis.

PMID- 9278039
TI  - Genomic stability. Silencing and DNA repair connect.

PMID- 9278040
TI  - RNA structure. A molecular contortionist.

PMID- 9278041
TI  - Autoimmune diabetes. Retrovirus as trigger, precipitator or marker?

PMID- 9278042
TI  - Protein-protein interactions. Calcium turns turquoise into gold.

PMID- 9278043
TI  - Morbillivirus in monk seal mass mortality.

PMID- 9278044
TI  - Alpha-synuclein in Lewy bodies.

PMID- 9278045
TI  - Endogenous proviruses as "mementos"?

PMID- 9278046
TI  - Biodegradable block copolymers as injectable drug-delivery systems.
AB  - Polymers that display a physicochemical response to stimuli are widely explored
      as potential drug-delivery systems. Stimuli studied to date include chemical
      substances and changes in temperature, pH and electric field. Homopolymers or
      copolymers of N-isopropylacrylamide and poly(ethylene oxide)-poly(propylene
      oxide)-poly(ethylene oxide) (known as poloxamers) are typical examples of
      thermosensitive polymers, but their use in drug delivery is problematic because
      they are toxic and non-biodegradable. Biodegradable polymers used for drug
      delivery to date have mostly been in the form of injectable microspheres or
      implant systems, which require complicated fabrication processes using organic
      solvents. Such systems have the disadvantage that the use of organic solvents can
      cause denaturation when protein drugs are to be encapsulated. Furthermore, the
      solid form requires surgical insertion, which often results in tissue irritation
      and damage. Here we report the synthesis of a thermosensitive, biodegradable
      hydrogel consisting of blocks of poly(ethylene oxide) and poly(L-lactic acid).
      Aqueous solutions of these copolymers exhibit temperature-dependent reversible
      gel-sol transitions. The hydrogel can be loaded with bioactive molecules in an
      aqueous phase at an elevated temperature (around 45 degrees C), where they form a
      sol. In this form, the polymer is injectable. On subcutaneous injection and
      subsequent rapid cooling to body temperature, the loaded copolymer forms a gel
      that can act as a sustained-release matrix for drugs.

PMID- 9278047
TI  - A neuronal population code for sound localization.
AB  - The accuracy with which listeners can locate sounds is much greater than the
      spatial sensitivity of single neurons. The broad spatial tuning of auditory
      neurons indicates that a code based on the responses of ensembles of neurons, a
      population code, must be used to determine the position of a sound in space. Here
      we show that the tuning of neurons to the most potent localization cue, the
      interaural time difference in low-frequency signals (< approximately 2kHz),
      becomes sharper as the information ascends through the auditory system. We also
      show that this sharper tuning increases the efficiency of the population code, in
      the sense that fewer neurons are required to achieve a given acuity.

PMID- 9278048
TI  - Loose-patch recordings of single quanta at individual hippocampal synapses.
AB  - Synapses in the central nervous system are typically studied by recording
      electrical responses from the cell body of the postsynaptic cell. Because neurons
      are normally connected by multiple synaptic contacts, these postsynaptic
      responses reflect the combined activity of many thousands synapses, and it
      remains unclear to what extent the properties of individual synapses can be
      deduced from the population response. We have therefore developed a method for
      recording the activity of individual hippocampal synapses. By capturing an
      isolated presynaptic bouton inside a loose-patch pipette and recording from the
      associated patch of postsynaptic membrane, we were able to detect miniature
      excitatory postsynaptic currents ('minis') arising from spontaneous vesicle
      exocytosis at a single synaptic site, and to compare these with minis recorded
      simultaneously from the cell body. The average peak conductance at a single
      synapse was about 900 pS, corresponding roughly to the opening of 90 AMPA-type
      glutamate-receptor channels. The variability in this conductance was about 30%,
      matching the value reported for the neuromuscular junction. Given that our
      synapses displayed single postsynaptic densities (PSDs), this variability is
      larger than would be predicted from the random opening of receptor channels,
      suggesting that they are not saturated by the content of a single vesicle.
      Therefore the response to a quantum of neurotransmitter at these synapses is not
      limited by the number of available postsynaptic receptors.

PMID- 9278049
TI  - Microglial activation by Alzheimer amyloid precursor protein and modulation by
      apolipoprotein E.
AB  - A role for beta-amyloid precursor protein (beta-APP) in the development of
      Alzheimer's disease has been indicated by genetics, and many conditions in which
      beta-APP is raised have been associated with an increased risk of Alzheimer's
      disease or an Alzheimer's-like pathology. Inflammatory events may also contribute
      to Alzheimer's disease. Here we investigate whether a secreted derivative of beta
      APP (sAPP-alpha) can induce inflammatory reactions in microglia, which are brain
      cells of monocytic lineage. We found that treatment with sAPP-alpha increased
      markers of activation in microglia and enhanced their production of neurotoxins.
      The ability of sAPP-alpha to activate microglia was blocked by prior incubation
      of the protein with apolipoprotein E3 but not apolipoprotein E4, a variant
      associated with an increased risk for Alzheimer's. A product of amyloidogenic
      beta-APP processing (sAPP-beta) also activated microglia. Because sAPP-beta is
      deficient in the neuroprotective activity shown by sAPP-alpha, our results
      indicate that increased amyloidogenic processing could adversely affect the
      balance of sAPP activities that determine neuronal viability.

PMID- 9278050
TI  - Fluorescent indicators for Ca2+ based on green fluorescent proteins and
      calmodulin.
AB  - Important Ca2+ signals in the cytosol and organelles are often extremely
      localized and hard to measure. To overcome this problem we have constructed new
      fluorescent indicators for Ca2+ that are genetically encoded without cofactors
      and are targetable to specific intracellular locations. We have dubbed these
      fluorescent indicators 'cameleons'. They consist of tandem fusions of a blue- or
      cyan-emitting mutant of the green fluorescent protein (GFP), calmodulin, the
      calmodulin-binding peptide M13, and an enhanced green- or yellow-emitting GFP.
      Binding of Ca2+ makes calmodulin wrap around the M13 domain, increasing the
      fluorescence resonance energy transfer (FRET) between the flanking GFPs.
      Calmodulin mutations can tune the Ca2+ affinities to measure free Ca2+
      concentrations in the range 10(-8) to 10(-2) M. We have visualized free Ca2+
      dynamics in the cytosol, nucleus and endoplasmic reticulum of single HeLa cells
      transfected with complementary DNAs encoding chimaeras bearing appropriate
      localization signals. Ca2+ concentration in the endoplasmic reticulum of
      individual cells ranged from 60 to 400 microM at rest, and 1 to 50 microM after
      Ca2+ mobilization. FRET is also an indicator of the reversible intermolecular
      association of cyan-GFP-labelled calmodulin with yellow-GFP-labelled M13. Thus
      FRET between GFP mutants can monitor localized Ca2+ signals and protein
      heterodimerization in individual live cells.

PMID- 9278051
TI  - Kinetochores distinguish GTP from GDP forms of the microtubule lattice.
AB  - During prometaphase in mitotic cell division, chromosomes attach to the walls of
      microtubules and subsequently move to microtubule ends, where they stay
      throughout mitosis. This end-attachment seems to be essential for correct
      chromosome segregating. However, the mechanism by which kinetochores, the
      multiprotein complexes that link chromosomes to the microtubules of the mitotic
      spindle, recognize and stay attached to microtubule ends is not understood. One
      clue comes from the hydrolysis of GTP that occurs during microtubule
      polymerization. Although tubulin dimers must contain GTP to polymerize, this GTP
      is rapidly hydrolysed following the addition of dimers to a growing polymer. This
      creates a microtubule consisting largely of GDP-tubulin, with a small cap of GTP
      tubulin at the end. It is possible that kinetochores distinguish the different
      structural states of a GTP- versus a GDP-microtubule lattice. We have examined
      this question in vitro using reconstituted kinetochores from the yeast
      Saccharomyces cerevisiae. We found that kinetochores in vitro bind preferentially
      to GTP- rather than GDP-microtubules, and to the plus-end preferentially over the
      lattice. Our results could explain how kinetochores stay at microtubule ends and
      thus segregate chromosomes correctly during mitosis in vivo. This result
      demonstrates that proteins exist that can distinguish the GTP conformation of the
      microtubule lattice.

PMID- 9278052
TI  - Mutant analysis links the translocon and BiP to retrograde protein transport for
      ER degradation.
AB  - Proteins enter the secretory pathway through the endoplasmic reticulum, which
      delivers properly folded proteins to their site of action and contains a quality
      control system to monitor and prevent abnormal proteins from being delivered.
      Many of these proteins are degraded by the cytoplasmic proteasome, which requires
      their retrograde transport to the cytoplasm. Based on a co-immunoprecipitation of
      major histocompatibility complex (MHC) class I heavy-chain breakdown
      intermediates with the translocon subunit Sec61p, it was speculated that Sec61p
      maybe involved in retrograde transport. Here we present functional evidence from
      genetic studies that Sec61p mediates retrograde transport of a mutated lumenal
      yeast carboxypeptidase ycsY (CPY*) in vivo. The endoplasmic reticulum lumenal
      chaperone BiP (Kar2p) and Sec63p, which are also subunits of the import
      machinery, are involved in export of CPY* to the cytosol. Thus our results
      demonstrate that retrograde transport of proteins is mediated by a functional
      translocon. We consider the export of endoplasmic reticulum-localized proteins to
      the cytosol by the translocon for proteasome degradation to be a general process
      in eukaryotic cell biology.

PMID- 9278053
TI  - Marking of active genes on mitotic chromosomes.
AB  - During development and differentiation, cellular phenotypes are stably propagated
      through numerous cell divisions. This epigenetic 'cell memory' helps to maintain
      stable patterns of gene expression. DNA methylation and the propagation of
      specific chromatin structures may both contribute to cell memory. There are two
      impediments during the cell cycle that can hinder the inheritance of specific
      chromatin configurations: first, the pertinent structures must endure the passage
      of DNA-replication forks in S phase; second, the chromatin state must survive
      mitosis, when chromatin condenses, transcription is turned off, and almost all
      double-stranded DNA-binding proteins are displaced. After mitosis, the previous
      pattern of expressed and silent genes must be restored. This restoration might be
      governed by mass action, determined by the binding affinities and concentrations
      of individual components. Alternatively, a subset of factors might remain bound
      to mitotic chromosomes, providing a molecular bookmark to direct proper chromatin
      reassembly. Here we analyse DNA at transcription start sites during mitosis in
      vivo and find that it is conformationally distorted in genes scheduled for
      reactivation but is undistorted in repressed genes. These protein-dependent
      conformational perturbations could help to re-establish transcription after
      mitosis by 'marking' genes for re-expression.

PMID- 9278054
TI  - Silencing factors participate in DNA repair and recombination in Saccharomyces
      cerevisiae.
AB  - DNA double-strand breaks are repaired by homologous recombination or DNA end
      joining, but the latter process often causes legitimate recombination and
      chromosome rearrangements. One of the factors involved in the end-joining process
      is Hdf1, a yeast homologue of Ku protein. We used the yeast two-hybrid assay to
      show that Hdf1 interacts with Sir4, which is involved in transcriptional
      silencing at telomeres and HM loci. Analyses of sir4 mutants showed that Sir4 is
      required for deletion by illegitimate recombination and DNA end-joining in the
      pathway involving Hdf1. Sir2 and Sir3, but not Sir1, were also found to
      participate in these processes. Furthermore, mutations of the SIR2, SIR3 and SIR4
      genes conferred increased sensitivity to gamma-radiation in a genetic background
      with a mutation of the RAD52 gene, which is essential for double-strand break
      repair mediated by homologous recombination. These results indicate that Sir
      proteins are involved in double-strand break repair mediated by end-joining. We
      propose that Sir proteins act with Hdf1 to alter broken DNA ends to create an
      inactivated chromatin structure that is essential for the rejoining of DNA ends.

PMID- 9278055
TI  - Crystal structure of the breakage-reunion domain of DNA gyrase.
AB  - DNA gyrase is a type II DNA topoisomerase from bacteria that introduces
      supercoils into DNA. It catalyses the breakage of a DNA duplex (the G segment),
      the passage of another segment (the T segment) through the break, and then the
      reunification of the break. This activity involves the opening and dosing of a
      series of molecular 'gates' which is coupled to ATP hydrolysis. Here we present
      the crystal structure of the 'breakage-reunion' domain of the gyrase at 2.8 A
      resolution. Comparison of the structure of this 59K (relative molecular mass,
      59,000) domain with that of a 92K fragment of yeast topoisomerase II reveals a
      very different quaternary organization, and we propose that the two structures
      represent two principal conformations that participate in the enzymatic pathway.
      The gyrase structure reveals a new dimer contact with a grooved concave surface
      for binding the G segment and a cluster of conserved charged residues surrounding
      the active-site tyrosines. It also shows how breakage of the G segment can occur
      and, together with the topoisomerase II structure, suggests a pathway by which
      the T segment can be released through the second gate of the enzyme. Mutations
      that confer resistance to the quinolone antibacterial agents cluster at the new
      dimer interface, indicating how these drugs might interact with the gyrase-DNA
      complex.

PMID- 9278056
TI  - Current limitations to protein threading approaches.
AB  - A short review of the threading approach to protein structure prediction,
      including presentation of some open statistical problems. Also discussed is one
      of the likely sources of the current limited success, that being the form of the
      pairwise potentials used in most threading approaches.

PMID- 9278057
TI  - Protein structure and energy landscape dependence on sequence using a continuous
      energy function.
AB  - We have recently described a new conformational search strategy for protein
      folding algorithms called the CGU (convex global underestimator) method. Here we
      use a simplified protein chain representation and a differentiable form of the
      Sun/Thomas/Dill energy function to test the CGU method. Standard search methods,
      such as Monte Carlo and molecular dynamics are slowed by kinetic traps. That is,
      the computer time depends more strongly on the shape of the energy landscape
      (dictated by the amino acid sequence) than on the number of degrees of freedom
      (dictated by the chain length). The CGU method is not subject to this limitation,
      since it explores the underside of the energy landscape, not the top. We find
      that the CGU computer time is largely independent of the monomer sequence for
      different chain folds and scales as O(n4) with chain length. By using different
      starting points, we show that the method appears to find global minima. Since we
      can currently find stable states of 36-residue chains in 2.4 hours, the method
      may be practical for small proteins.

PMID- 9278058
TI  - Lattice and off-lattice side chain models of protein folding: linear time
      structure prediction better than 86% of optimal.
AB  - This paper considers the protein energy minimization problem for lattice and off
      lattice protein folding models that explicitly represent side chains. Lattice
      models of proteins have proven useful tools for reasoning about protein folding
      in unrestricted continuous space through analogy. This paper provides the first
      illustration of how rigorous algorithmic analyses of lattice models can lead to
      rigorous algorithmic analyses of off-lattice models. We consider two side chain
      models: a lattice model that generalizes the HP model (Dill, 1985) to explicitly
      represent side chains on the cubic lattice and a new off-lattice model, the HP
      Tangent Spheres Side Chain model (HP-TSSC), that generalizes this model further
      by representing the backbone and side chains of proteins with tangent spheres. We
      describe algorithms with mathematically guaranteed error bounds for both of these
      models. In particular, we describe a linear time performance guaranteed
      approximation algorithm for the HP side chain model that constructs conformations
      whose energy is better than 86% of optimal in a face-centered cubic lattice, and
      we demonstrate how this provides a better than 70% performance guarantee for the
      HP-TSSC model. Our analysis provides a mathematical methodology for transferring
      performance guarantees on lattices to off-lattice models. These results partially
      answer the open question of Ngo et al. (1994) concerning the complexity of
      protein folding models that include side chains.

PMID- 9278059
TI  - An iterative method for improved protein structural motif recognition.
AB  - We present an iterative algorithm that uses randomness and statistical techniques
      to improve existing methods for recognizing protein structural motifs. Our
      algorithm is particularly effective in situations where large numbers of
      sufficiently diverse examples of the motif are not known. These are precisely the
      situations that pose significant difficulties for previously known methods. We
      have implemented our algorithm and we demonstrate its performance on the coiled
      coil motif. We test our program LearnCoil on the domain of 3-stranded coiled
      coils and subclasses of 2-stranded coiled coils. We show empirically that for
      these motifs, our method overcomes the problem of limited data.

PMID- 9278060
TI  - Local rules for protein folding on a triangular lattice and generalized
      hydrophobicity in the HP model.
AB  - We consider the problem of determining the three-dimensional folding of a protein
      given its one-dimensional amino acid sequence. We use the HP model for protein
      folding proposed by Dill (1985), which models protein as a chain of amino acid
      residues that are either hydrophobic or polar, and hydrophobic interactions are
      the dominant initial driving force for the protein folding. Hart and Istrail
      (1996a) gave approximation algorithms for folding proteins on the cubic lattice
      under the HP model. In this paper, we examine the choice of a lattice by
      considering its algorithmic and geometric implications and argue that the
      triangular lattice is a more reasonable choice. We present a set of folding rules
      for a triangular lattice and analyze the approximation ratio they achieve. In
      addition, we introduce a generalization of the HP model to account for residues
      having different levels of hydrophobicity. After describing the biological
      foundation for this generalization, we show that in the new model we are able to
      achieve similar constant factor approximation guarantees on the triangular
      lattice as were achieved in the standard HP model. While the structures derived
      from our folding rules are probably still far from biological reality, we hope
      that having a set of folding rules with different properties will yield more
      interesting folds when combined.

PMID- 9278061
TI  - Las Vegas algorithms for gene recognition: suboptimal and error-tolerant spliced
      alignment.
AB  - Recently, Gelfand, Mironov and Pevzner (1996) proposed a spliced alignment
      approach to gene recognition that provides 99% accurate recognition of human
      genes if a related mammalian protein is available. However, even 99% accurate
      gene predictions are insufficient for automated sequence annotation in large
      scale sequencing projects and therefore have to be complemented by experimental
      gene verification. One hundred percent accurate gene predictions would lead to a
      substantial reduction of experimental work on gene identification. Our goal is to
      develop an algorithm that either predicts an exon assembly with accuracy
      sufficient for sequence annotation or warns a biologist that the accuracy of a
      prediction is insufficient and further experimental work is required. We study
      suboptimal and error-tolerant spliced alignment problems as the first steps
      towards such an algorithm, and report an algorithm which provides 100% accurate
      recognition of human genes in 37% of cases (if a related mammalian protein is
      available). In 52% of genes, the algorithm predicts at least one exon with 100%
      accuracy.

PMID- 9278062
TI  - Improved splice site detection in Genie.
AB  - We present an improved splice site predictor for the genefinding program Genie.
      Genie is based on a generalized Hidden Markov Model (GHMM) that describes the
      grammar of a legal parse of a multi-exon gene in a DNA sequence. In Genie,
      probabilities are estimated for gene features by using dynamic programming to
      combine information from multiple content and signal sensors, including sensors
      that integrate matches to homologous sequences from a database. One of the
      hardest problems in genefinding is to determine the complete gene structure
      correctly. The splice site sensors are the key signal sensors that address this
      problem. We replaced the existing splice site sensors in Genie with two novel
      neural networks based on dinucleotide frequencies. Using these novel sensors,
      Genie shows significant improvements in the sensitivity and specificity of gene
      structure identification. Experimental results in tests using a standard set of
      annotated genes showed that Genie identified 86% of coding nucleotides correctly
      with a specificity of 85%, versus 80% and 84% in the older system. In further
      splice site experiments, we also looked at correlations between splice site
      scores and intron and exon lengths, as well as at the effect of distance to the
      nearest splice site on false positive rates.

PMID- 9278063
TI  - Automated gene identification in large-scale genomic sequences.
AB  - Computational methods for gene identification in genomic sequences typically have
      two phases: coding region recognition and gene parsing. While there are a number
      of effective methods for recognizing coding regions (exons), parsing the
      recognized exons into proper gene structures, to a large extent, remains an
      unsolved problem. We have developed a computer program which can automatically
      parse the recognized exons into gene models that are most consistent with the
      available Expressed Sequence Tags (ESTs) and a set of biological heuristics,
      derived empirically. The gene modeling algorithm used in this program provides a
      general framework for applying EST information so the modeling accuracy improves
      as the amount of available EST information increases. Based on preliminary tests
      on a number of large DNA sequences, using the dbEST database, we have observed
      that the algorithm can (1) accurately model complicated multiple gene structures,
      including embedded genes, (2) identify falsely-recognized exons and locate missed
      exons by the initial exon recognition phase, and (3) make more accurate exon
      boundary predictions, if the necessary EST information is available. We have
      extended this EST-based gene modeling algorithm to model genes on unfinished DNA
      contigs at the end of the shotgun sequencing. This extended version can
      automatically determine the orientations and the relative order of the DNA
      contigs (with gaps between them) using the available ESTs as reference models,
      before the gene modeling phase.

PMID- 9278064
TI  - Aligning a DNA sequence with a protein sequence.
AB  - We develop several algorithms for the problem of aligning DNA sequence with a
      protein sequence. Our methods account for frameshift errors, but not for introns
      in the DNA sequence. Thus, they are particularly appropriate for comparing a cDNA
      sequence that suffers from sequencing errors with an amino acid sequence or a
      protein sequence database. We describe algorithms for computing optimal
      alignments for several definitions of DNA-protein alignment, verify sufficient
      conditions for equivalence of certain definitions, describe techniques for
      efficient implementation, and discuss experience with these ideas in a new
      release of the FASTA suite of database-searching programs.

PMID- 9278065
TI  - Sequence alignment with tandem duplication.
AB  - Algorithm development for comparing and aligning biological sequences has, until
      recently, been based on the SI model of mutational events which assumes that
      modification of sequences proceeds through any of the operations of substitution,
      insertion or deletion (the latter two collectively termed indels). While this
      model has worked fairly well, it has long been apparent that other mutational
      events occur. In this paper, we introduce a new model, the DSI model which
      includes another common mutational event, tandem duplication. Tandem duplication
      produces tandem repeats which are common in DNA, making up perhaps 10% of the
      human genome. They are responsible for some human diseases and may serve a
      multitude of functions in DNA regulation and evolution. Using the DSI model, we
      develop new exact and heuristic algorithms for comparing and aligning DNA
      sequences when they contain tandem repeats.

PMID- 9278066
TI  - ReAligner: a program for refining DNA sequence multi-alignments.
AB  - We present a round-robin realignment algorithm that improves a potentially crude
      initial alignment of an assembled collection of DNA sequence fragments, as might,
      for example, be output by a typical fragment assembly program. The algorithm uses
      a weighted combination of two scoring schemes to achieve superior multi
      alignments, and employs a banded dynamic programming variation to achieve a
      running time that is linear in the amount of sequence in the data set. We
      demonstrate that the algorithm improves upon the alignments produced by other
      assembly programs in a series of empirical experiments on simulated data.
      Finally, we present a pair of programs embodying the algorithms that are
      available from the Web site ftp://ftp.cs.arizona.edu/realigner.

PMID- 9278067
TI  - New flexible approaches for multiple sequence alignment.
AB  - The multiple sequence alignment problem is applicable and important in various
      fields in molecular biology such as the prediction of three-dimensional
      structures of proteins and the inference of phylogenetic trees. However, the
      optimal alignment based on the scoring criterion is not always biologically the
      most significant alignment. We here propose two flexible and efficient approaches
      to solve this problem. One approach is to provide many suboptimal alignments as
      alternatives for the optimal one. It has been considered almost impossible to
      investigate such suboptimal alignments of more than two sequences because of the
      enormous size of the problem. We propose techniques for enumeration of suboptimal
      alignments using the Eppstein algorithm. We also discuss what kind of suboptimal
      alignment is unnecessary to enumerate and propose an efficient enumeration
      algorithm to enumerate only necessary alignments. The other approach is
      parametric analysis. The obtained optimal solution with fixed parameters such as
      gap penalties is not always the biologically best alignment. Thus, it is required
      to vary parameters and check how the optimal alignments change. The way to vary
      parameters has been studied well on the problem of two sequences, but not on the
      multiple alignment problem because of the difficulty of computing the optimal
      solution. We propose techniques for this parametric multiple alignment problem
      and examine the features of alignments obtained by various parametric analyses.
      For both approaches, this paper performs experiments on various groups of actual
      protein sequences and examines the efficiency of these algorithms and properties
      of sequence groups.

PMID- 9278069
TI  - The prospective, randomized, double-blind clinical trial in orthopaedic surgery.

PMID- 9278068
TI  - The deferred path heuristic for the generalized tree alignment problem.
AB  - Many multiple alignment methods implicitly or explicitly try to minimize the
      amount of biological change implied by an alignment. At the level of sequences,
      biological change is measured along a phylogenetic tree, a structure frequently
      being predicted only after the multiple alignment instead of together with it.
      The Generalized Tree Alignment problem addresses both questions simultaneously.
      It can formally be viewed as a Steiner tree problem in sequence space and our
      approach merges a path heuristic for the construction of a Steiner tree with a
      clustering method as usually applied only to distance data. This combination is
      achieved using sequence graphs, a data structure for efficient representation of
      similar sequences. Although somewhat slower in practice than an earlier method by
      Hein (1989) the current approach achieves significantly better results in terms
      of the underlying scoring function. Furthermore, a variant of the algorithm is
      introduced that maintains a guaranteed error bound of (2 - 2/n) for n sequences.

PMID- 9278070
TI  - Resurfacing of the patella in total knee arthroplasty. A prospective, randomized,
      double-blind study.
AB  - During a two-year period, eighty-nine patients who were scheduled to have a total
      knee arthroplasty for the treatment of degenerative osteoarthrosis were randomly
      assigned to one of two groups: resurfacing of the patella or retention of the
      patella. All patients received the same posterior cruciate-sparing prosthesis,
      and all operations were performed by, or under the direct supervision of, one of
      us. Three patients died in the early postoperative period. The remaining eighty
      six patients (118 knees; fifty-eight that had had resurfacing of the patella and
      sixty that had not) formed the study group. They were followed for a mean of
      thirty months (range, twenty-four to forty-four months). Evaluation was performed
      with use of the clinical scoring system of The Knee Society, a patient
      satisfaction questionnaire, specific questions regarding patellofemoral symptoms
      and function, and radiographs. All clinical evaluations were performed by the
      same research nurse, without the involvement of a physician, in a blinded manner
      (neither the nurse nor the patient had knowledge of whether the patella had been
      resurfaced). Preoperatively, the mean Knee Society score, on a scale ranging from
      0 to 200 points, was 89.7 points (range, 33 to 132 points); postoperatively, this
      score improved to a mean of 172.7 points (range, 98 to 200 points). With the
      numbers available for study, we could detect no significant difference between
      the knees that had had patellar resurfacing and those that had not with regard to
      the over-all score (p = 0.63), the subscore for pain (p = 0.56), or the subscore
      for function (p = 0.77). We also could detect no difference between the treatment
      groups, with the numbers available, with regard to patient satisfaction or the
      responses to questions involving the function of the patellofemoral joint,
      including the ability to exit from an automobile, to rise from a chair, and to
      climb stairs. Thirty-two patients had bilateral total knee replacement with
      resurfacing of the patella in one knee and retention of the patella in the other.
      These patients expressed no clear preference for either knee. Eight (13 per cent)
      of the sixty knees that had not had resurfacing were painful anteriorly compared
      with four (7 per cent) of the fifty-eight that had; this was not a significant
      difference (p = 0.38), with the numbers available. The anterior pain that was
      noted postoperatively was predominantly of new onset; it had not been observed
      preoperatively in three of the four knees that had had resurfacing or in four of
      the eight that had not. No additional treatment options were offered to the
      patients who had anterior pain in the knee after resurfacing. However, six (10
      per cent) of the sixty knees that had not had resurfacing had it subsequently,
      because of anterior pain in the knee, after the twelfth postoperative month
      (range, fifteen to thirty-nine months). The pain decreased in four of these
      knees. Thus, total knee arthroplasty with retention of the patella yielded
      clinical results that were comparable with those after total knee arthroplasty
      with patellar resurfacing, but it was associated with a 10 per cent prevalence of
      the need for subsequent resurfacing. The prevalence of anterior pain after total
      knee arthroplasty was not influenced by whether or not the patella had been
      resurfaced. The postoperative clinical scores, the postoperative development of
      anterior pain, and the need for subsequent resurfacing were not predicted by the
      presence of preoperative anterior pain, obesity, or the grade of chondromalacia
      observed intraoperatively. Because of the short duration of follow-up, these
      results should be considered preliminary. Additional follow-up is planned.

PMID- 9278071
TI  - Stimulation of proteoglycan synthesis in explants of porcine articular cartilage
      by recombinant osteogenic protein-1 (bone morphogenetic protein-7).
AB  - Osteogenic protein-1 (also known as bone morphogenetic protein-7) is a member of
      the bone morphogenetic protein family. Bone morphogenetic proteins and related
      members of the TGF-beta (transforming growth factor-beta) superfamily are
      involved in the development and repair of bone. Recombinant bone morphogenetic
      proteins induce the formation of new cartilage and bone at heterotopic sites. We
      investigated the influence of recombinant osteogenic protein-1 (at doses of
      three, ten, thirty, or 100 nanograms per milliliter) on the synthesis and release
      of proteoglycans and the maintenance of a steady-state concentration of
      proteoglycans in explants of porcine articular cartilage that were maintained in
      chemically defined serum-free medium. We found a dose-dependent stimulation of
      proteoglycan synthesis and a concurrent decrease in the rate of release of
      proteoglycans from the explants. The size of the proteoglycan monomers and the
      composition of the glycosaminoglycan chains in the untreated articular cartilage
      were similar to those in the articular cartilage treated with osteogenic protein
      1. The capacity of the newly synthesized proteoglycan monomers to form aggregates
      with exogenous hyaluronic acid was found to be similar to that of proteoglycans
      in bovine nasal cartilage. Our results demonstrated that osteogenic protein-1
      stimulated the synthesis of proteoglycans and diminished the release of
      proteoglycans from explants of porcine articular cartilage. CLINICAL RELEVANCE:
      The maintenance and repair of articular cartilage is a formidable challenge in
      clinical orthopaedics. The stimulation of proteoglycan synthesis by osteogenic
      protein-1 (bone morphogenetic protein-7) in explants of cartilage maintained in
      chemically defined serum-free medium implies that recombinant osteogenic protein
      1 may play a role in the maintenance of a steady-state concentration of
      proteoglycans in articular cartilage, a desirable prerequisite for optimum repair
      of cartilage. Osteogenic protein-1 can initiate the formation of cartilage from
      mesenchymal cells. Once new cartilage has formed at the site of repair,
      osteogenic protein-1 also may maintain the synthesis of proteoglycans.

PMID- 9278072
TI  - Publication patterns of papers presented at the Annual Meeting of The American
      Academy of Orthopaedic Surgeons.
AB  - Publication in a peer-reviewed journal is the ultimate lasting acknowledgment of
      an author's research results. Numerous clinical and basic-science papers are
      presented at the Annual Meeting of The American Academy of Orthopaedic Surgeons,
      but not all of these presentations culminate in publication in a peer-reviewed
      journal. In an effort to determine the percentages and patterns of publication,
      every presentation from the 1990, 1991, and 1992 meetings (a total of 1465
      presentations) was reviewed with use of a Melvyl Medline Plus computer search
      during the summer of 1996. The presentations were classified on the basis of
      subspecialty. The over-all rate of publication by August 1996 was 46 per cent
      (668 of 1465), and the rates were similar for the 1990, 1991, and 1992 meetings.
      The average time to publication was twenty months, and most publications appeared
      within three years after presentation, with a plateau thereafter. Basic-science
      presentations had the highest rate of publication: 64 per cent (eighteen of
      twenty-eight presentations). The rates of publication by clinical subspecialty
      ranged from 39 per cent (twenty-eight of seventy-two presentations in the hand
      subspecialty and eighty-two of 210 presentations in the trauma subspecialty) to
      53 per cent (110 of 206 presentations in the spine subspecialty). There was no
      significant difference among these groups (p = 0.611, chi-square test). The
      American volume of The Journal of Bone and Joint Surgery published the most
      papers (24 per cent; 161 of the 668 publications), followed by Clinical
      Orthopaedics and Related Research (16 per cent; 106 of 668). The over-all rate of
      publication of presentations at the Annual Meeting of The American Academy of
      Orthopaedic Surgeons is comparable with reported rates in other medical
      specialties.

PMID- 9278074
TI  - Arthroscopic release of postoperative capsular contracture of the shoulder.
AB  - A loss of motion after an operation on the shoulder often cannot be treated
      successfully with physical therapy or closed manipulation. Although open release
      techniques generally improve motion, they involve extensive dissection. We
      developed a technique of arthroscopic capsular release and applied it in eighteen
      patients who had postoperative stiffness of the shoulder. The patients were
      selected for the arthroscopic release technique if a conservative program of
      physical therapy and an attempted closed manipulation had failed to restore
      motion and if they had no known extra-articular contractures. Five of the
      thirteen patients who had had a global loss of shoulder motion had motion
      restored with the anterior capsular release, and six needed an additional release
      of the posterior aspect of the capsule--that is, a combined (anterior and
      posterior) capsular release. The arthroscopic procedure could not be completed in
      the remaining two patients because of an extra-articular scar involving the
      subscapularis, but those patients were managed successfully with an open release.
      As five patients had lost only internal rotation and flexion, they had only a
      posterior capsular release. For the eleven patients who had had either an
      anterior or a combined (anterior and posterior) capsular release, the mean
      improvement in the score of Constant and Murley was 43 points (range, 31 to 62
      points) and all improvements in motion were significant (p < 0.01). Flexion
      improved a mean of 51 degrees (range, 10 to 65 degrees); external rotation in
      adduction and abduction, 31 degrees (range, 10 to 50 degrees) and 40 degrees
      (range, 5 to 80 degrees), respectively; and internal rotation in adduction and
      abduction, six spinous-process levels (range, three to eleven levels) and 41
      degrees (range, 20 to 70 degrees), respectively. For the five patients who had an
      isolated posterior capsular release, the score of Constant and Murley improved a
      mean of 20 points (range, 5 to 35 points) and the improvements in motion also
      were significant (p < 0.05 and 0.005). Internal rotation in adduction and
      abduction improved a mean of four spinous-process levels (range, one to ten
      levels) and 42 degrees (range, 30 to 60 degrees), respectively. Eight patients
      had an arthroscopic acromioplasty for concomitant impingement disease. One
      patient who had had a combined (anterior and posterior) release and one who had
      had a posterior capsular release continued to have pain because of injury of the
      articular cartilage from a previous operation. We concluded that arthroscopic
      capsular release is a reliable method for restoring motion with minimum morbidity
      in carefully selected patients who have postoperative stiffness of the shoulder.
      When necessary, it can be converted to an open release.

PMID- 9278073
TI  - Prediction of correction of scoliosis with use of the fulcrum bending radiograph.
AB  - We used a new method to assess spinal flexibility in thirty patients who were to
      be managed operatively for adolescent idiopathic scoliosis. The method involves
      placing the patient in the lateral decubitus position and bent over a fulcrum (a
      radiolucent padded cylinder) so that the spine is passively hinged open. For
      thoracic curves the fulcrum is centered under the rib corresponding to the apex
      of the curve, and for lumbar curves the fulcrum is placed directly under the
      apex. The preoperative workup for the thirty patients included an anteroposterior
      radiograph made with the patient standing, a lateral-bending radiograph made with
      the patient supine, and the new fulcrum bending radiograph. All patients were
      treated with posterior spinal arthrodesis with segmental spinal instrumentation.
      The degree of flexibility obtained with the traditional and new methods was
      compared with the degree of correction observed on the radiograph made, with the
      patient standing, one week after the operation. Preoperatively, the mean Cobb
      angle was 58 degrees on the anteroposterior radiograph made with the patient
      standing, 31 degrees on the lateral-bending radiograph made with the patient
      supine, and 24 degrees on the fulcrum bending radiograph. The mean angle was 25
      degrees on the anteroposterior radiograph made one week postoperatively, so the
      mean correction was 57 per cent. The difference between the mean angle on the
      lateral-bending radiograph and that on the postoperative radiograph was
      significant (p < 0.001); however, the mean angle measured on the preoperative
      fulcrum bending radiograph and the postoperative angle were almost identical. We
      found the fulcrum bending radiograph to be more predictive of the degree of
      flexibility and correctability than the lateral-bending radiograph in this group
      of patients who had segmental spinal instrumentation for correction of idiopathic
      scoliosis.

PMID- 9278075
TI  - Suprascapular neuropathy. Results of non-operative treatment.
AB  - We retrospectively reviewed the results of non-operative treatment of
      suprascapular neuropathy in fifteen patients seen between November 1983 and
      February 1991. The clinical diagnosis was confirmed with electrodiagnostic
      studies. The treatment consisted of a program of physical therapy to improve the
      range of motion of the shoulder and to strengthen the surrounding muscles. The
      average duration of follow-up was three years and eleven months (range, one year
      to eight years and ten months). The latest evaluation included electrodiagnostic
      studies of the affected extremity and dynamic isokinetic testing of both upper
      extremities. The result was excellent for five patients and good for seven. The
      three remaining patients had operative treatment because of persistent symptoms;
      one of these patients had an excellent result, one had a good result, and one had
      a poor result. The results suggest that, in the absence of a well defined lesion
      producing mechanical compression of the suprascapular nerve, suprascapular
      neuropathy should be treated non-operatively.

PMID- 9278076
TI  - Glenohumeral joint translations before and after total shoulder arthroplasty. A
      study in cadavera.
AB  - The purpose of the present study was to examine the motions of natural and
      prosthetically reconstructed glenohumeral joints without capsular contracture in
      the laboratory to obtain a better understanding of joint motion as it may relate
      to failure of the implant. Seven joints from fresh-frozen human cadavera were
      instrumented with a six-degrees-of-freedom magnetic tracking device to study
      patterns of translation and rotation with and without the application of
      simulated muscle forces (active and passive models). The specimens were tested
      before and after reconstruction of the joint with use of modified operative
      techniques and implants that had from zero to five millimeters of radial mismatch
      between the humeral head and glenoid components. The natural and reconstructed
      joints had similar patterns of translation, with larger rotations and
      translations observed in the passive model. On the average, the active
      translations of the natural joints were best reproduced by the reconstructed
      joints with less conforming articulations. The mean active translation in the
      natural joints was 1.5 millimeters along the anterior-posterior axis and 1.1
      millimeters along the superior-inferior axis. The active translations in the
      reconstructed joints were observed to increase consistently as the conformity of
      the components decreased: the mean active anterior-posterior translations ranged
      from 0.3 millimeter for conforming components to 1.7 millimeters for components
      with a five-millimeter radial mismatch, and the mean active superior-inferior
      translations ranged from 0.4 to 1.1 millimeters. The patterns of translation
      during passive motions were less consistent, presumably because of the influence
      of capsular ligaments and because the translations were large enough for the
      articular surface of the humeral head to lose contact with the articular surface
      of the glenoid component. CLINICAL RELEVANCE: Glenohumeral translations during
      active motions were found to depend on articular conformity, which indicates that
      the choice of implants may have important consequences for normal motions.
      Totally conforming designs may impose a degree of restraint to translations that
      is higher than that in the natural joint. The patterns of translation may
      influence the longevity of the joint replacement with respect to stability,
      loosening of the glenoid component, and wear of the components.

PMID- 9278077
TI  - Single-level posterolateral arthrodesis, with or without posterior decompression,
      for the treatment of isthmic spondylolisthesis in adults. A prospective,
      randomized study.
AB  - Forty-two neurologically intact adults in whom non-operative treatment of grade-I
      or grade-II isthmic spondylolisthesis of the most caudad lumbar segment had
      failed were entered into a prospective study of the results of operative
      treatment. Twenty patients who smoked were managed with a posterolateral
      arthrodesis with instrumentation (transpedicular fixation), and twenty-two
      patients who did not smoke were managed with a posterolateral arthrodesis without
      instrumentation. Of the patients who were managed with instrumentation, eight
      were randomized to treatment with a decompressive laminectomy and twelve, to
      treatment without it; in the group that was managed without instrumentation, the
      distribution was ten and twelve patients, respectively. The patients were
      followed clinically for a mean of 4.5 years (range, 3.5 to six years). Of the
      eighteen patients who had been managed with decompression, four had a
      pseudarthrosis and six had an unsatisfactory result compared with none and one of
      the twenty-four who had been managed without decompression (p = 0.02 and p =
      0.01, respectively). In the group of twenty patients (smokers) who had been
      managed with instrumentation, none of the twelve managed without decompression
      had a pseudarthrosis compared with one of the eight managed with decompression (p
      = 0.2). In the group of twenty-two patients (non-smokers) who had been managed
      without instrumentation, none of the twelve managed without decompression had a
      pseudarthrosis compared with three of the ten managed with decompression (p =
      0.04). In the group managed with instrumentation, two of the eight who had had
      decompression had an unsatisfactory result compared with none of the twelve who
      had not had decompression. In the group managed without instrumentation, four of
      the ten who had had decompression had an unsatisfactory result compared with one
      of the twelve who had not had decompression. The addition of decompression to
      arthrodesis, performed with or without instrumentation, for the treatment of low
      grade isthmic spondylolisthesis in patients who do not have a serious
      neurological deficit does not appear to improve the result and may significantly
      increase the rates of pseudarthrosis and unsatisfactory results.

PMID- 9278078
TI  - Long-term results of total hip replacement in young patients who had ankylosing
      spondylitis. Eighteen to thirty-year results with survivorship analysis.
AB  - We determined the long-term results of total hip replacement in a series of young
      patients who had ankylosing spondylitis. Between 1966 and 1978, forty-three
      Charnley low-friction arthroplasties were performed in twenty-four patients who
      had an average age of 28.8 years (range, nineteen to thirty-nine years) at the
      time of the operation. There were seventeen men and seven women. The average
      duration of follow-up for the series was 22.7 years (range, one month [a
      perioperative death] to 30.3 years). Four patients (seven hips) had died an
      average of 12.6 years (range, one month to 18.7 years) after the operation. The
      twenty surviving patients had clinical and radiographic follow-up until the time
      of writing or until both of the original components had been revised. All
      patients had substantial relief of pain and improvement of function and the range
      of motion of the joint. Twenty-one patients (88 per cent; thirty-nine hips) were
      completely free of pain (6 points, according to the scale of Merle d'Aubigne and
      Postel), and the remainder had only slight discomfort (5 points). Ten acetabular
      components and one femoral component were revised because of aseptic loosening,
      and one patient had a revision of both components because of late deep infection.
      Three additional femoral components were revised during a revision operation for
      a loose acetabular component. Although the femoral components were not loose,
      they had been in place for more than ten years and it was thought likely that the
      bearing surface was damaged. The average time to revision was 13.3 years (range,
      4.0 to 20.3 years). At an average of 22.7 years, thirty-eight (88 per cent) of
      the original femoral components and thirty-two (74 per cent) of the original
      acetabular components remained in situ. The average annual rate of acetabular
      wear was 0.12 millimeter for the entire series. Only six hips (14 per cent) had
      minor heterotopic ossification, and none of the hips had clinically important
      ossification (class III or IV according to the system of Brooker et al.). To our
      knowledge, the present report describes the largest series of total hip
      arthroplasties, with the longest duration of follow-up, in young patients who had
      ankylosing spondylitis. Survivorship analysis with use of the Kaplan-Meier method
      revealed that the probability of survival of the femoral component (with 95 per
      cent confidence intervals) was 91 per cent (83 to 99 per cent) at twenty years
      and 83 per cent (72 to 94 per cent) at thirty years. The probability of survival
      of the acetabular components was 73 per cent (61 to 84 per cent) at twenty years
      and 70 per cent (57 to 83 per cent) at thirty years. The probability that both
      components would survive was 91 per cent (82 to 100 per cent) at ten years, 73
      per cent (61 to 84 per cent) at twenty years, and 70 per cent (57 to 83 per cent)
      at thirty years. The Charnley low-friction arthroplasty provided consistently
      good long-term results, with a low rate of complications and revisions, in this
      group of young patients.

PMID- 9278079
TI  - A comparison of fixation screws for the scaphoid during application of cyclical
      bending loads.
AB  - Matched pairs of scaphoids from cadavera were stressed with ramped intensity
      cyclical bending loads after osteotomy and fixation of one scaphoid with a
      Herbert screw and fixation of the other with an AO 3.5-millimeter cannulated
      screw, a Herbert-Whipple screw, an Acutrak cannulated screw, or a Universal
      Compression screw. The AO screw, Acutrak screw, and Herbert-Whipple screw
      demonstrated superior resistance to cyclical bending loads compared with the
      Herbert screw. The Universal Compression screw did not provide better fixation
      than the Herbert screw because of fractures that occurred at the time of
      insertion. The AO screw and the Herbert screw were then tested in a separate
      setup in which a segment of volar cortex had been removed in addition to the
      simple osteotomy. The loss of volar cortex greatly diminished the quality of the
      fixation provided by both of the screws during application of ramped intensity
      cyclical bending loads. CLINICAL RELEVANCE: A fixation device in the scaphoid
      must be able to withstand the stresses that are placed on the scaphoid as a
      result of its position spanning the proximal and distal carpal rows. Also,
      because of the prolonged time required for healing of fractures or non-unions of
      the scaphoid, the device must be able to withstand many such cycles of stress.
      The present study demonstrates that commonly used screws for fixation of the
      scaphoid vary significantly (p < 0.005) in their ability to resist cyclical
      bending loads.

PMID- 9278080
TI  - The effect of active movement of the foot on venous blood flow after total hip
      replacement.
AB  - Surgeons often encourage patients to move their feet in an attempt to prevent
      venous stasis, but there is little evidence that this measure is beneficial. We
      investigated the effect of active movement of one foot on the venous blood flow
      four days after total hip replacement. The actual venous outflow at rest was
      measured with use of venous occlusion strain-gauge plethysmography in thirty
      eight patients. The patients were randomly allocated to the control group
      (eighteen patients) or the exercise group (twenty patients). A baseline
      measurement was followed by a one-minute period of rest (control group) or of
      maximum plantar flexion and dorsiflexion of the foot, ankle, and toes at a rate
      of thirty cycles per minute (exercise group). The venous outflow was measured
      again at two, seven, twelve, and thirty minutes in both groups. Movement of the
      foot for one minute produced a significant and sustained increase (p < 0.002) in
      the venous outflow (mean maximum increase, 22 per cent). The value remained
      greater than the baseline level for thirty minutes (mean increase, 6.5 per cent)
      (p < 0.2). The increase was gradual, reaching a maximum twelve minutes after the
      completion of exercise. Our results confirm the beneficial hemodynamic effects of
      active movement of the foot in the postoperative period and suggest that patients
      should move the feet and ankles postoperatively as part of a prophylactic regimen
      directed at decreasing the risk of venous thrombosis.

PMID- 9278081
TI  - The influence of patient-related factors and the position of the acetabular
      component on the rate of dislocation after total hip replacement.
AB  - The senior one of us performed 438 primary and 181 revision total hip
      arthroplasties with use of so-called modern prostheses between July 1983 and
      January 1994. Fifty-three patients, who had had forty-seven primary procedures
      and twelve revisions, either died or were lost to follow-up less than two years
      after the operation and were excluded from the study. The results for the
      remaining 446 patients (391 primary procedures and 169 revisions) were analyzed
      to determine the influence of patient-related and operative factors and the
      position of the acetabular component on the rate of dislocation. Dislocation
      occurred after thirty-two (6 per cent) of the 560 total hip arthroplasties:
      seventeen (4 per cent) of the 391 primary procedures and fifteen (9 per cent) of
      the 169 revisions (p = 0.046). There was no relationship between the variables of
      age, gender, obesity, or preoperative diagnosis and dislocation after either
      primary or revision arthroplasty. Seven (23 per cent) of the thirty
      arthroplasties in the patients who had a history of excessive intake of alcoholic
      beverages (more than 2.1 liters [seventy-two ounces] of beer or more than 0.2
      liter [six ounces] of other alcoholic beverages a day) were followed by a
      dislocation compared with twenty-five (5 per cent) of the 530 arthroplasties in
      the patients who did not have such a history. This difference was significant for
      the patients who had had a revision arthroplasty (p = 0.00005), but with the
      numbers available we could not detect a difference for those who had had a
      primary arthroplasty (p = 0.264). Radiographic analysis was performed for thirty
      two hips that had dislocated and thirty-two that had not (seventeen primary
      procedures and fifteen revisions in each group), matched exactly according to the
      type of prosthesis and the operative approach (but not age). We detected no
      association between either the version or the abduction angle of the acetabular
      component (within the range of 39 to 56 degrees for the primary prostheses and 38
      to 57 degrees for the revision prostheses) and the risk of dislocation. Thirty of
      the thirty-two hips in each group had an abduction angle of the acetabular
      component that was in the so-called safe range of 30 to 50 degrees.

PMID- 9278082
TI  - Semiconstrained total elbow replacement for the treatment of post-traumatic
      osteoarthrosis.
AB  - Forty-one consecutive patients were managed for post-traumatic osteoarthrosis or
      dysfunction of the elbow with use of a non-customized semiconstrained Coonrad
      Morrey total elbow prosthesis. The average age at the time of the operation was
      fifty-seven years (range, thirty-two to eighty-two years). The patients were
      followed for an average of five years and eight months (range, two to twelve
      years). Radiographs were made at least two years postoperatively (average, five
      years and one month; range, two to twelve years) for thirty-nine of the forty-one
      patients. According to the Mayo elbow performance score, sixteen patients (39 per
      cent) had an excellent result, eighteen (44 per cent) had a good result, five (12
      per cent) had a fair result, and two (5 per cent) had a poor result. Thirty-six
      (95 per cent) of the thirty-eight patients who had a functioning implant at the
      time of follow-up considered the outcome to be satisfactory. Preoperatively,
      thirty-seven patients (90 per cent) had moderate or severe pain; postoperatively,
      thirty (73 per cent) had no or only mild discomfort. Motion improved from an
      average arc of flexion of 40 to 118 degrees preoperatively to an average arc of
      flexion of 27 to 131 degrees postoperatively. All thirty-eight functioning
      implants rendered the elbow stable. Eleven patients (27 per cent) had a major
      complication. Nine of them (22 per cent of the series) needed an additional
      operation. There was no aseptic loosening, and most of the complications were
      primarily due to so-called mechanical failure. The ulnar component fractured in
      five patients (12 per cent), and the polyethylene bushings wore out in two (5 per
      cent). These complications were attributed principally to the performance of
      strenuous physical labor, such as lifting more than ten kilograms on a regular
      basis, against the advice of the surgeon; excessive preoperative deformity of the
      joint; or an unstable traumatic injury. Two patients (5 per cent) had an
      infection. Semiconstrained joint replacement of the elbow can be a reliable form
      of treatment, and frequently is the only viable option, for the difficult
      problems encountered with post-traumatic destruction of a joint. Restoration of
      function, relief of pain, and patient satisfaction can be achieved even when a
      patient is less than sixty years old if that patient has low demands and a low
      level of activity. However, the mechanical failures underscore the fact that this
      procedure is relatively contraindicated in patients who anticipate strenuous
      physical activity or who are not expected to comply with the postoperative
      protocol. This observation reflects the tendency for increased and excessive use
      of a previously functionless joint, after it has been rendered stable and pain
      free, to lead to mechanical failure.

PMID- 9278083
TI  - Biomechanical evaluation of the medial collateral ligament of the elbow.
AB  - Anatomical dissection and biomechanical testing were used to study twenty-eight
      cadaveric elbows in order to determine the role of the medial collateral ligament
      under valgus loading. The medial collateral ligament was composed of anterior,
      posterior, and occasionally transverse bundles. The anterior bundle was, in turn,
      composed of anterior and posterior bands that tightened in reciprocal fashion as
      the elbow was flexed and extended. Sequential cutting of the ligament was
      performed while rotation caused by valgus torque was measured. The anterior band
      of the anterior bundle was the primary restraint to valgus rotation at 30, 60,
      and 90 degrees of flexion and was a co-primary restraint at 120 degrees of
      flexion. The posterior band of the anterior bundle was a co-primary restraint at
      120 degrees of flexion and a secondary restraint at 30 and 90 degrees of flexion.
      The posterior bundle was a secondary restraint at 30 degrees only. The reciprocal
      anterior and posterior bands have distinct biomechanical roles and theoretically
      may be injured separately. The anterior band was more vulnerable to valgus
      overload when the elbow was extended, whereas the posterior band was more
      vulnerable when the elbow was flexed. The posterior bundle was not vulnerable to
      valgus overload unless the anterior bundle was completely disrupted. The intact
      elbows rotated a mean of 3.6 degrees between the neutral position and the two
      newton-meter valgus torque position. Cutting of the entire anterior bundle caused
      an additional 3.2 degrees of rotation at 90 degrees of flexion, where the effect
      was greatest. CLINICAL RELEVANCE: Physical findings in a patient who has an
      injury of the anterior bundle may be subtle, and an examination should be
      performed with the elbow in 90 degrees of flexion for greatest sensitivity. As
      the anterior bundle is the major restraint to valgus rotation, reconstructive
      procedures should focus on anatomical reproduction of that structure. Parallel
      limbs of tendon graft placed from the inferior aspect of the medial epicondyle to
      the area of the sublimis tubercle will simulate the reciprocal bands of the
      anterior bundle. Temporary immobilization with the elbow in flexion may relax the
      critically important anterior band of the reconstruction during healing.

PMID- 9278084
TI  - Non-union of the ulna in a ten-month-old child who had type-IV hereditary sensory
      neuropathy. A case report.

PMID- 9278085
TI  - Neuropathic spinal arthropathy in Charcot-Marie-Tooth disease. A case report.

PMID- 9278086
TI  - Fistula between the hip and the sigmoid colon after total hip arthroplasty. A
      case report.

PMID- 9278087
TI  - Limb-lengthening, skeletal reconstruction, and bone transport with the Ilizarov
      method.

PMID- 9278088
TI  - Anti-inflammatory medication after muscle injury. A treatment resulting in short
      term improvement but subsequent loss of muscle function.

PMID- 9278089
TI  - Coronal shear fractures of the distal end of the humerus.

PMID- 9278090
TI  - Compartment syndromes associated with postoperative epidural analgesia. A case
      report.

PMID- 9278091
TI  - Role of subunit diversity in signaling by heterotrimeric G proteins.
AB  - The heterotrimeric G proteins are extensively involved in the regulation of cells
      by extracellular signals. The receptors that control them are often the targets
      of drugs. There are many isoforms of each of the three subunits that make up
      these proteins. Thus far, genes for at least sixteen alpha subunits, five beta
      subunits, and eleven gamma subunits have been identified. In addition, some of
      these proteins have splice variants or are differentially modified. Based upon
      what is already known, there are well over a thousand possible G protein
      heterotrimer combinations. The role of subunit diversity in heterotrimer
      formation and its effect on signaling by G proteins are still not well
      understood. However, many current lines of research are leading toward an
      understanding of these roles. The functional significance of subunit
      heterogeneity is related to the mechanisms used by G proteins to transmit and
      integrate the many signals coming into cells through this system. Described here
      are the basic mechanisms by which G proteins integrate cellular responses, the
      possible role of subunit heterogeneity in these mechanisms, and the evidence for
      and against their physiological significance. Recent studies suggest the likely
      possibility that subunit heterogeneity plays an important role in signaling by G
      proteins. This role has the potential to extend substantially the flexibility of
      G proteins in mediating cellular responses to extracellular signals. However, the
      details of this are yet to be worked out, and they are the subject of many
      different avenues of research.

PMID- 9278092
TI  - Biological imaging and the molecular basis of dopaminergic diseases.
AB  - The development and validation of preclinical biological probes of nigrostriatal
      dysfunction are part of the next frontier for battling diseases involving
      dopamine deficiency. In this work, the quantitative relationship relationship
      between radiofluorinated L-DOPA, [e.g., L-3,4-dihydroxy-6
      [18F]fluorophenylalanine (6-[18F]fluoro-L-DOPA, FDOPA)] kinetics measured with
      positron emission tomography and central dopamine biochemistry is discussed. A
      hypothesis of a possible "non-linearity" of FDOPA kinetics with dopaminergic cell
      losses is presented to explain apparent discrepancies in post-mortem biochemical
      and histological determinations in Parkinson's disease. Similar observations have
      been made in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-exposed monkeys
      and human subjects where the FDOPA uptake constantly fell within normal values
      unless severe nigral damage had occurred. The limitations of FDOPA, and other
      biological probes, for examining the asymptomatic phase of dopaminergic diseases
      and the future direction of research are discussed.

PMID- 9278093
TI  - Differential effect of vanadate on receptor-mediated endocytosis of the
      asialoglycoprotein receptor in hepatocytes from normal and diabetic rats.
AB  - Insulin-dependent diabetes has been shown to affect several aspects of receptor
      mediated endocytosis. Since vanadate, a phosphate analogue, is known to exert
      insulin-like actions in target tissues, we studied the effects of vanadate on the
      endocytosis of the asialoglycoprotein receptor (ASGP-R) after its administration
      either in vivo (oral therapy) and/or in vitro by direct incubation of isolated
      hepatocytes with vanadate. The surface binding, internalization, and degradation
      of 3H-asialoorosomucoid (3H-ASOR), a prototype ligand of the ASGP-R, were
      decreased in diabetic rats by approximately 36.5%, 22.3%, and 12.9%,
      respectively. These values were normalized in diabetic rats treated by vanadate.
      Similarly, vanadate treatment normalized the biphasic dissociation of 3H
      ASOR/ASGP-R complexes by restoring the rapid dissociation process. In contrast,
      vanadate treatment did not affect any of these endocytic parameters in normal
      rats. In vitro experiments were monitored by direct incubation of isolated
      hepatocytes with 10 mM vanadate. This incubation created an inhibitory effect on
      the endocytic parameters. In this work, we have demonstrated that vanadate
      treatment can reverse the alterations induced by diabetes on receptor-mediated
      endocytosis of the ASGP-R.

PMID- 9278094
TI  - Ribavirin conjugated with lactosaminated poly-L-lysine: selective delivery to the
      liver and increased antiviral activity in mice with viral hepatitis.
AB  - Ribavirin (RIBV) is a useful drug in the treatment of chronic type C hepatitis
      but displays a toxicity for red blood cells (RBC), which limits its dosage and
      necessitates withdrawal in some patients. Selective concentration of RIBV in
      liver should improve therapeutic results. Liver targeting can be achieved by
      coupling the drug to galactosyl-terminating peptides, which specifically enter
      hepatocytes. In the present work, we conjugated RIBV to lactosaminated poly-L
      lysine (L-Poly(Lys)), a hepatotropic carrier enabling intramuscular (IM)
      administration of conjugates. The L-Poly(Lys)-RIBV conjugate had a heavy drug
      load (312-327 microg of RIBV in 1 mg of conjugate) and was very soluble in 0.9%
      NaCl (200 mg/mL). The conjugate was devoid of acute toxicity in mouse. When
      incubated with human or mouse blood, it did not release the drug. After IM
      administration to mice, the conjugate was selectively taken up by the liver,
      where the drug was released in a pharmacologically active form. This was
      demonstrated using mice infected with a strain of murine hepatitis virus (MHV)
      sensitive to RIBV. Coupled RIBV, IM injected, inhibited MHV replication in liver
      at a daily dose two to three times lower than that of the free drug. In mice IM
      injected with a conjugate tritiated in the RIBV moiety, the ratios between the
      levels of radioactivity in liver and RBC were two times higher than in animals
      injected with free tritiated RIBV. In conclusion, the present results support the
      possibility that the chemotherapeutic index of RIBV in chronic type C hepatitis
      can be increased by conjugation with L-Poly(Lys).

PMID- 9278095
TI  - Antiproliferative effects of imidazo[1,2-a]pyrazine derivatives on the Dami cell
      line.
AB  - Since cyclic 3',5'-adenosine monophosphate (cAMP) is involved in cell
      proliferation and as previous data showed that imidazo[1,2-alpha]pyrazine
      derivatives (PAB12, PAB30, PAB40, SCA40, SCA41, and SCA44) inhibited cAMP
      breakdown by a phosphodiesterase (PDE)-inhibitory effect, the aim of the present
      study was to investigate the effects of these derivatives on proliferation of the
      Dami cell line in relation with their actions on cAMP content and on PDE
      isoenzymes isolated from Dami cells. SCA41 and SCA44 inhibited cell growth in a
      dose-dependent manner, while SCA40 and PAB40 induced a weak inhibition. Growth
      inhibitions were 40%, 91%, and 60% for SCA41, SCA44 (at 100 microM), and IBMX (at
      100 microM), respectively, and could not be related to their effects on cAMP
      levels. In addition, although all compounds potentiated cAMP formation by
      prostaglandin E1 (PGE1), no potentiations were observed when the
      antiproliferative effects of SCA41 and SCA44 were considered. Investigation of
      derivatives on PDE isoenzymes III, IV, and V indicated non-selective PDE
      inhibitory effects for SCA41 and SCA44, while SCA40 elicited preferences for type
      III, and PAB30 and PAB40 preferences for type IV isoenzymes. These effects could
      not totally explain the antiproliferative activity of the derivatives. The
      activation of P2 purinoceptors by imidazo[1,2-a]pyrazine did not lead to their
      antiproliferative effects. Thus, the mechanism of the antiproliferative effects
      of the compounds remains to be determined. It does, however, depend on the
      chemical substitutions of the imidazo[1,2-a]pyrazine skeleton and in particular
      on the 2-carbonitrile presence and the length of the 8-aminoaliphatic group.

PMID- 9278096
TI  - pH-dependent regulation of camptothecin-induced cytotoxicity and cleavable
      complex formation by the antimalarial agent chloroquine.
AB  - Two classes of drugs interact with DNA topoisomerase (topo) I, namely topoI
      poisons such as the camptothecins, which create DNA single-strand breaks and the
      catalytic inhibitors, which do not. Here, we demonstrate that the antimalarial
      agent chloroquine is a catalytic inhibitor of eukaryote topoI, as the drug
      inhibited topoI-mediated DNA relaxation. Chloroquine is known to be a topoII
      catalytic inhibitor and as such is able to inhibit the activity of a topoII
      poison, i.e. etoposide. We now show that chloroquine also inhibits the topol
      poison camptothecin as camptothecin-stimulated nicking of plasmid DNA was
      inhibited by chloroquine. These observations also apply to endogenous topoI in
      whole cells. Accordingly, camptothecin-induced single-strand breaks as well as
      cytotoxicity were antagonised by chloroquine. Further, in a band depletion assay
      in whole cells, chloroquine prevented camptothecin-mediated topoI trapping,
      indicating that chloroquine inhibits topoI by interfering with the DNA binding
      step of the enzyme. In contrast to camptothecin, chloroquine is a weak base and
      therefore does not enter the cell if the extracellular fluid is acidic, as is the
      case in most solid tumors. This leads to the possibility of directing
      cytotoxicity to solid tumors with low extracellular pH by combining a neutral
      anticancer agent, i.e. camptothecin with a weak base antagonist, i.e.
      chloroquine. To test the feasibility of this principle, we investigated the drug
      combination at varying extracellular pH. We found that the antagonising effect of
      chloroquine on camptothecin-mediated trapping of topoI and DNA single-strand
      break formation was abolished at acidic extracellular pH. In a clonogenic assay,
      camptothecin in combination with chloroquine selectively killed cells at low pH
      (6.2), while camptothecin cytotoxicity was antagonised by chloroquine at normal
      pH (7.2). In conclusion, we show that the topoI catalytic inhibitor chloroquine
      inhibits camptothecin and that chloroquine can target the cytotoxic effect of
      camptothecin to tumor cells in acidic environments.

PMID- 9278097
TI  - Expression and purification of recombinant human N-formyl-L-leucyl-L
      phenylalanine (FMLP) receptor: generation of polyclonal antibody against FMLP
      receptor.
AB  - The recombinant formyl peptide receptor has been successfully expressed and
      purified, utilizing an Escherichia coli expression system. Purification of formyl
      peptide receptor was performed using gel filtration chromatography and affinity
      chromatography, and the purified protein migrated at an apparent molecular mass
      of 36,000 Da. The purified recombinant receptor retained functional activity as
      determined by a ligand binding assay. The yield of the recombinant purified
      receptor was approximately 1 mg/2 L of culture, and the binding activity was
      determined to be approximately 8 nM, which suggests the conclusion that
      glycosylation does not affect significantly ligand binding of the N-formyl-L
      leucyl-L-phenylalanine (FMLP) receptor molecule. The recombinant receptor protein
      yield was found to be significantly higher than that obtained from neutrophils.
      The purified recombinant receptor was then utilized to generate antibody against
      the same. The reaction of the antibody against recombinant formylpeptide receptor
      and against native formylpeptide receptor on neutrophils was confirmed by western
      blot analysis and flow cytometric analysis, respectively. The antibody was also
      used successfully to detect recombinant formylpeptide receptor expression on
      transfected 293 cells. These results describe for the first time the expression,
      purification, and characterization of recombinant FMLP receptor with ligand
      binding activity and the generation of polyclonal antibody against the same. This
      work also provides a foundation for future biophysical studies of the FMLP
      receptor molecule, which have not been possible until now.

PMID- 9278098
TI  - Effects of a chronic lithium treatment on central dopamine neurotransporters.
AB  - The objectives of this study were to characterize the effects of a chronic
      lithium (Li+) treatment on dopamine (DA) uptake sites, as well as on the levels
      of mRNA encoding for these transporters, and to determine the eventual
      reversibility of the treatment. Quantitative autoradiography was carried out on
      sections from rat brain using 3beta-(4-[125I]iodophenyl)tropane-2beta-carboxylic
      acid isopropyl ester ([125I]RT1-121) to label DA transporters, and mRNA levels
      were measured by in situ hybridization. Following chronic Li+ treatment (28
      days), the labelling to DA transporters increased (60-90%) in all sections of the
      rostral and caudal neostriatum, whereas no alteration was observed in the other
      regions studied, namely the substantia nigra, the ventral tegmental area, and the
      dorsal raphe nucleus. These effects were reversed completely following a
      withdrawal period of 2 days without Li+. Also, there were no modifications in the
      labelling of DA transporters after only 2 days of Li+ treatment. In addition, we
      measured the levels of mRNA encoding for DA transporters in the substantia nigra
      and the ventral tegmental area; however, no alterations were observed following a
      chronic Li+ treatment, and thus the hypothesis of an increased synthesis is not
      supported. This could mean that the Li+ treatment modified the affinity of DA
      transporters for the radioligand, possibly a consequence of conformational
      changes induced by the disruption of the nerve terminal membrane environment;
      however, a modification in the number of transporters could not be ruled out. The
      results of this study further support the hypothesis of the implication of
      central dopaminergic transmission in the pathology and treatment of affective
      disorders.

PMID- 9278099
TI  - Receptor-mediated endocytosis of angiotensin II in rat myometrial cells.
AB  - The events involved in the processing of the angiotensin II (Ang II)-receptor
      complex were studied in primary cultures of rat myometrial cells. Ang II bound to
      rat myometrial cells in a specific, time- and temperature-dependent fashion.
      Pretreatment with cycloheximide did not interfere with binding up to 3 hr, but
      inhibited increases in binding observed over longer periods. The [3H]Ang II
      binding to intact cells was inhibited by dithiothreitol (DTT), and the rank order
      of potency of Ang II and nonpeptide antagonists to inhibit the [3H]Ang II binding
      was Ang II > Losartan >> PD 123319 or CGP 42112B, indicating the presence of the
      AT1 receptor type. Whereas most of the [3H]Ang II binding at 4 degrees was
      susceptible to acid or pronase treatment, binding at 35 degrees was resistant to
      both treatments, suggesting an internalization of the Ang II-receptor complex.
      Phenylarsine oxide (PAO) and N-ethylmaleimide (NEM) caused a concentration
      dependent inhibition when the binding assay was performed at 35 degrees, but no
      effect was observed at 4 degrees, indicating that these agents did not alter cell
      surface binding but actually prevented the internalization process. Simultaneous
      treatment with 1 mM DTT or beta-mercaptoethanol prevented the inhibitory effect
      of NEM, but only DTT could prevent the inhibition caused by PAO, indicating that
      two closely located sulfhydryl groups must be involved in the internalization
      process. Chloroquine (100 microM) inhibited the [3H]Ang II dissociation from
      cells, and monensin (25 microM) induced a 30% inhibition of [3H]Ang II binding
      (35 degrees, 3 hr), suggesting endosomal processing of the Ang II-receptor
      complex with receptor recycling to the cell surface. These results indicate that
      Ang II binding to AT1 receptors in rat myometrial cells is followed by
      internalization of the Ang II-receptor complex and recycling of the receptor to
      the cell surface.

PMID- 9278100
TI  - Inhibition of nitric oxide synthase with pyrazole-1-carboxamidine and related
      compounds.
AB  - Guanidines, amidines, S-alkylisothioureas, and other compounds containing the
      amidine function (-C(=NH)NH2) have been described as inhibitors of the generation
      of nitric oxide (NO) by NO synthase (NOS). Here we report on the inhibition of
      the activity of NOS isoforms by compounds in which the amidine function is
      attached to a nitrogen of 1,2-diazo heterocycles to form N-carboxamidines and
      related compounds. 1H-Pyrazole-1-carboxamidine HCl (PCA) inhibited the activity
      of purified inducible NOS (iNOS), endothelial NOS (eNOS), and neuronal NOS (nNOS)
      isoforms to a similar extent (IC50 = 0.2 microM). 3-Methyl-PCA and 4-methyl-PCA
      showed reduced potencies, but a preference for iNOS [IC50 = 5 and 2.4 microM,
      respectively; cf. N(G)-methyl-L-arginine (NMA) IC50 = 6 microM]. Inhibition of
      purified iNOS by PCAs could be reversed completely by excess L-arginine, while
      their inhibition of NO production by stimulated RAW macrophages could be reversed
      by transfer to a drug-free medium. This suggests a competitive mode of
      inhibition. PCA caused potent concentration-dependent inhibition of the
      acetylcholine-induced, endothelium-dependent relaxations of precontracted rat
      thoracic aorta (IC50 = 30 microM). 4-Methyl-PCA inhibited the relaxations only at
      > or = 300 microM. In contrast, 4-methyl-PCA was more effective than both PCA and
      NMA in restoring the ex vivo contractility of aortic rings taken from
      lipopolysaccharide-treated rats. PCA and NMA, but not 4-methyl-PCA, caused marked
      increases in mean arterial pressure when administered i.v. to anesthetized rats.
      In conclusion, PCA and related compounds caused potent inhibition of NOS.
      Substitution of the pyrazole ring reduced potency, but improved selectivity
      towards iNOS as exemplified by 4-methyl-PCA.

PMID- 9278101
TI  - Mutagenic consequences of the incorporation of 6-thioguanine into DNA.
AB  - 6-Thioguanine (S6G) has been used in the treatment of acute leukemias because of
      its cytotoxic effect on proliferating leukemic cells. The cytotoxicity of S6G is
      thought to derive from its incorporation into DNA in place of guanine. The
      deoxyribonucleoside triphosphate of S6G, SdGTP, is a good substrate for bacterial
      and human DNA polymerases (Ling et al., Mol Pharmacol 40: 508-514, 1991). Since
      SdGTP was observed to misincorporate in place of adenine at a greater frequency
      than did dGTP, it appeared plausible that this analog could produce more subtle
      effects (mutations) due to mispairing with thymine. To assess whether such
      mutations occur, SdGTP was incorporated into the lacI gene of phage M13lacISaXb
      in reactions that omitted dGTP (-G) or dATP (-A). LacI mutation frequency was
      determined by beta-galactosidase colorimetric staining (inactivation of the lac
      repressor results in blue plaques in the absence of inducer). When a high
      concentration of SdGTP (24 microM) was used in the DNA polymerase reaction, phage
      infectivity was inhibited. When a relatively low concentration (2.4 nM) was added
      to the -G and -A reactions, mutagenic effects were observed. DNA sequencing of
      mutant progeny arising from the -G + S6G reaction revealed C-to-T base
      transitions and some C-to-A transversions. Similarly, the presence of SdGTP in
      the -A reactions led to mutants with T-to-C transitions. No insertions or
      deletions were observed. These data indicate that mispairing of S6G with thymine
      leads to mutagenic effects in this assay.

PMID- 9278102
TI  - Characterization of the induction of rat microsomal cytochrome P450 by tacrine.
AB  - The effect of multiple-dose tacrine (THA) administration at 2 and 20 mg/kg
      (single oral doses for 2 weeks) on cytochrome P450 (CYP) was examined in male and
      female Wistar rats. Changes in CYP were determined by measuring total spectral
      CYP, the rates of ethoxy- and pentoxyresorufin dealkylations, and the protein
      expression of several CYPs by western blot analysis of liver microsomes. Animals
      treated with beta-naphthoflavone or phenobarbital were employed as positive
      controls. No physiological or metabolic changes were observed in male or female
      rats treated with 2 mg/kg THA for 2 weeks. Male and female animals treated with
      20 mg/kg THA for 2 weeks demonstrated increased CYP1A activity (increased
      ethoxyresorufin deethylase activity) and increased expression of CYP1A1 with only
      minor increases in CYP1A2 expression. Compared with the effects of beta
      naphthoflavone induction of CYP1A, the induction observed with THA at 20 mg/kg
      was considered minor.

PMID- 9278103
TI  - Diagnostic value of fine needle aspiration biopsy for breast fibroadenoma
      diagnosis.
AB  - The diagnostic value of fine needle aspiration biopsy was estimated in the study.
      Cytological features, which allow us to diagnose and distinguish fibroadenoma
      from other breast benign lesions, were also examined. The diagnostic
      effectiveness was estimated depending on the observance of the described criteria
      (features) characteristic for the breast fibroadenoma by a comparative analysis
      of cytological findings in three diagnostic centers.

PMID- 9278104
TI  - Influence of LEPK on biochemical activity and morphology in situ of liver Golgi
      apparatus from control and streptozotocin-diabetic rats.
AB  - This paper presents yields of Golgi-rich membrane isolation, the activity of
      galactosyltransferase (GalT), the marker enzyme of Golgi apparatus as well as the
      morphology of the organelle from the livers in situ, in two groups of rats. One
      group consisted of control rats injected twice intraperitoneally with LEPK.
      Second group consisted of rats injected with LEPK and additionally after 24hrs
      given streptozotocin (SZ) to induce experimental diabetes. The results were
      compared with our previous investigations in control and diabetic rats. In the
      latter the activity of GalT was diminished, therefore diminishing glycosylation
      ability, and destructing Golgi apparatus morphology. This experiment shows that
      two-fold injection of LEPK prior to SZ does not prevent from changes in such
      biochemical parameters as free blood glucose level, yield of liver Golgi
      membranes isolation or total activity of GalT. For the first time in c. 30% of
      investigated rats the inactive enzyme of Golgi apparatus was found in the rats
      treated with LEPK+SZ. Morphological investigations of liver Golgi apparatus in
      rats treated with LEPK show slightly increased secretory activity with similar to
      untreated control rats morphological structure of this organelle. In the rats
      treated with LEPK and SZ the same morphological changes as in diabetic liver were
      found, however, such dramatic alterations as in SZ-diabetic rats were never
      found, irrespective of active or inactive GalT.

PMID- 9278105
TI  - Adaptation of the pancreas to repeated caerulein administration in rats. A
      morphological and functional study.
AB  - We studied the ability of the pancreas in the aspect of histological, biochemical
      and functional changes (pancreatic blood flow, serum and pancreatic amylase
      levels, DNA and RNA content and pancreatic mass) to recover from repeated
      episodes of caerulein-induced acute pancreatitis. The experiment was carried out
      in three animal groups: group I receiving one infusion of caerulein, group II
      receiving two infusions of caerulein at the interval of 10 days, and group III
      with three infusions every 10 days. It was found that histological signs of acute
      pancreatitis after the first caerulein infusion showed regression after 3 days,
      and the process of regeneration was almost completed after 10 days. The content
      of DNA and RNA correlated with the histological picture. At this time interval
      also the level of amylase was returning to normal. Each subsequent infusion of
      caerulein resulted in less enhanced tissue destruction, but regeneration started
      later. Pancreatic blood flow was decreased each time after induction of
      pancreatitis, whereas normalization was more rapid. The present findings indicate
      that the pancreas adapts to repeated injury, which is manifested by decreased
      severity of changes, but the process of regeneration is delayed.

PMID- 9278106
TI  - Short-term eradication therapy for Helicobacter pylori does not reduce the
      incidence of gastric metaplasia in duodenal ulcer patients.
AB  - The presence of gastric metaplasia in the duodenal mucosa and Helicobacter pylori
      infection play an important role in the development of duodenal ulcers and the
      risk for ulcer relapses. The purpose of the present study was to identify the
      presence of gastric metaplasia in the duodenum and observation of changes in its
      extent during eradication therapy for Helicobacter pylori. The study population
      consisted of 40 patients, 15 women (aged from 29 to 65 years) and 25 men (aged
      from 22 to 62 years). At baseline and after 6 weeks all patients underwent
      endoscopic examinations of the upper alimentary tract during which two gastric
      antral and duodenal biopsies were obtained. The first endoscopy revealed the
      presence of duodenal ulcers in 22 patients, no ulcers in 11 cases, and
      postulceration scar in the duodenal bulb in 7 cases. The specimens were stained
      with hematoxylin and eosin, Giemsa and periodic acid Schiff/Alcian Blue. On first
      examination Helicobacter pylori infection in gastric antral specimens was
      detected in 40 patients. Therapy with amoxycillin, metronidazole, ventrisol and
      omeprazole for two weeks was administered in patients without duodenal ulcers and
      with omeprazole and ventrisol for additional 14 days in patients with duodenal
      ulcers. After therapy the presence of Helicobacter pylori was found in 10 cases,
      thus the degree of Hp eradication in the present study was 75%. Gastric
      metaplasia in duodenal samples was seen in 15 patients with duodenal ulcers and
      in 10 nonulcer patients. After therapy only in 4 cases gastric metaplasia was
      reduced along with Hp eradication, whereas in 9 cases gastric metaplasia in the
      duodenum was still present despite effective Hp eradication. The present findings
      indicate that gastric metaplasia is a reversible lesion, although this process is
      not dynamic and requires more time. The presence of gastric metaplasia in the
      duodenum after Hp eradication indicates an increased risk for the recurrence of
      duodenal ulcers, thus providing a useful information for a clinician.

PMID- 9278107
TI  - The diagnostic value of cytomorphological traits in low and high risk type HPV
      infections.
AB  - The purpose of the study was to establish the diagnostic value of
      cytomorphological traits present in cervical smears in determining HPV infection.
      We examined 528 women, most of them between 18 and 34 years of age and sexually
      active, for the prevalence of HPV infection and compared the results of HPV DNA
      detection with the presence of cytomorphological traits of HPV infection in their
      cervical smears. The Digene Hybride Capture System technique was employed to
      detect HPV DNA in cytological material; cervical smears were examined by an
      experienced pathologist, who did not have prior knowledge of the HPV DNA test
      results. None of the cytomorphological traits examined proved to be pathognomonic
      for HPV infection. The diagnosis of HPV infection cannot be determined with
      certainty by a routine cytological examination. Only 15% of cervical smears from
      women infected with HPV showed classic cytomorphological traits of HPV infection 
      koilocytosis and/or dyskeratosis. We conclude that if more than three non
      classic traits of HPV infection are found in a cervical smear, HPV infection can
      be suspected.

PMID- 9278108
TI  - Tumour cell proliferation rate as determined by MIB-1 antibody in Wilms' tumour.
AB  - Determination of neoplastic cell proliferation becomes an important and objective
      element of assessing malignancy of neoplasms and their response to therapy. The
      basic problem in the management of Wilms' tumours in children is selection of
      patients to appropriate risk groups. The purpose of the present study was to
      evaluate proliferation index in 35 Wilms' tumours determined
      immunohistochemically by using monoclonal antibody MIB-1. The final analysis
      included 39 preparations of formalin fixed and paraffin embedded tissue sections.
      Proliferation index of neoplastic cells was determined in blastema, epithelium
      and stroma of the tumours. We found a marked difference between low proliferation
      index in stromal cells and high proliferation index in blastemal and epithelial
      cells. In tumours after chemotherapy we found higher proliferation index in
      epithelial cells and lower index in blastemal cells as compared to tumours before
      chemotherapy. Higher proliferation index in blastemal cells and epithelial cells
      was associated with worse prognosis. Worse prognosis was seen in cases in which
      after chemotherapy proliferation index in blastemal cells was still high.

PMID- 9278109
TI  - Light and electron microscopic examination of skeletal muscles in the reversed
      passive Arthus reaction.
AB  - The reversed passive Arthus reaction (RPAR) was performed in the dorsal area of
      the skin and skeletal muscles of the pelvic girdle of male guinea pigs. Biopsies
      were taken 3, 24 and 48 hours after antibody administration. In the dermal type
      of RPAR attention was paid to the structure of striated muscles of the
      subcutaneous panniculus carnosus. Histological and electron microscopic studies
      were performed. Changes in the dermal RPAR were more rapid and more intensive
      than those directly in the muscles. In both types of RPAR the affected muscle
      fibres demonstrated vacuolar and hyaline degeneration, segmental necrosis,
      internal nuclei, cellular infiltration, phagocytosis and regeneration in the late
      phase of reaction. Neutrophils predominated in the infiltrations after 3 hrs but
      after 24 and 48 hrs the main cells were macrophages and lymphocytes.
      Ultrastructural studies showed various stages of damage to the mitochondria,
      dispersion and disruption of the myofibrils and formation of tubular structures.
      A similar morphological appearance is characteristic of polymyositis (pm) and
      dermatomyositis (dm) suggesting a similar i.e. immune complex mechanism of muscle
      fibre damage in RPAR and in pm and dm.

PMID- 9278110
TI  - Computerised expert system for the morphological diagnosis of the
      glomerulonephritis.

PMID- 9278111
TI  - Gingival granular cell myoblastoma in newborns. Report of two cases.
AB  - Granular cell myoblastoma is a relatively rare and, exceptionally, malignant
      tumor. Here we report on two cases found in the gingiva in newborns. None of the
      previously described congenital lesions has been malignant. The treatment is
      always wide surgical excision and observation for possible recurrence. Neuron
      Specific Enolase (NSE) and S-100 protein immunoperoxidase studies revealed that
      cells of the granular cell myoblastoma react positively for both antigens, thus
      confirming the neurogenic origin of this tumor.

PMID- 9278112
TI  - Predisposition to gastric dilatation-volvulus in relation to genetics of thoracic
      conformation in Irish setters.
AB  - Thoracic depth/width ratios (TDWRs) were calculated from measurements of the
      parents (i.e., common dam and two sires) and puppies in two litters of Irish
      setters. The TDWRs of the parents, distribution of TDWRs in the litters, and
      comparisons with earlier population studies suggest that an incompletely dominant
      major gene and a background of minor genes and environmental factors are
      responsible for the TDWR. A history of gastric dilatation-volvulus (GDV) (i.e.,
      bloat) was correlated with high TDWRs in this family as it was for Irish setters
      and certain other breeds studied earlier. It may be possible to reduce the
      incidence of GDV by selective breeding of dogs with lower TDWRs.

PMID- 9278114
TI  - Esophagostomy tubes for feeding and decompression: clinical experience in 29
      small animal patients.
AB  - Esophagostomy tubes were placed surgically in 13 dogs and 16 cats. The placement
      technique used was rapid and only required curved forceps, a scalpel blade, and
      suture material. Flexible tubes (5- to 30-French) were used for feeding liquids
      or blenderized diets for up to 557 days. Additionally, esophageal and gastric
      decompression were accomplished using these tubes. Following tube removal, all
      ostomy wounds healed by second intention without evidence of esophageal stricture
      or esophagocutaneous fistula. Complications included kinking, placement in an
      inappropriate location, obstruction, inflammation or infection of the ostomy
      site, and reflux of feedings.

PMID- 9278113
TI  - Nephrotic syndrome resulting in thromboembolic disease and disseminated
      intravascular coagulation in a dog.
AB  - Thromboembolic disease and progression to disseminated intravascular coagulation
      (DIC) are potential life-threatening complications for dogs with nephrotic
      syndrome. Platelet count, prothrombin time (PT), activated partial thromboplastin
      time (APTT), plasma concentration of fibrinogen degradation products (FDPs),
      antithrombin III (ATIII), protein C, and plasminogen were used to identify
      hemostatic abnormalities in a dog with nephrotic syndrome. Pulmonary
      thromboembolic disease was diagnosed by thoracic radiography, arterial blood gas
      analysis, and pulmonary scintigraphy. Prompt recognition and treatment of
      hemostatic complications is necessary in dogs with nephrotic syndrome.

PMID- 9278115
TI  - Esophagostomy tubes as a method of nutritional management in cats: a
      retrospective study.
AB  - The use of esophagostomy tubes in 60 feline patients was evaluated
      retrospectively. Indications for tube placement, complications associated with
      placement and management, duration of treatment, and change in patient body
      weight were evaluated. Hepatic disease was the most common indication for tube
      placement. A minor complication associated with the surgical technique for tube
      placement was observed in three cases. Inflammation or infection of the tube
      site, swelling of the head, or vomition of the tube were observed complications
      during management in 19 cases. Vomiting occurred and was a complicating factor in
      nine cases. The average duration of tube placement was 23 days, and most patients
      maintained or gained weight while being fed through their esophagostomy tubes.

PMID- 9278116
TI  - Idiopathic, asymptomatic thrombocytopenia in Cavalier King Charles spaniels: 11
      cases (1983-1993).
AB  - The medical records of 11 Cavalier King Charles spaniels with idiopathic,
      asymptomatic thrombocytopenia and large-to-giant platelets were identified from a
      10-year retrospective search using the Veterinary Medical Data Base at Purdue
      University. Eight of the dogs had been treated with various immunosuppressive
      drugs. Six of the treated dogs remained thrombocytopenic, one was not
      reevaluated, and one developed a normal platelet count. The underlying etiology
      of idiopathic, asymptomatic thrombocytopenia in Cavalier King Charles spaniels
      has not been identified, but this condition could represent a congenital
      macrothrombocytopenic disorder.

PMID- 9278117
TI  - Thrombocytopenia in dogs with anticoagulant rodenticide-induced hemorrhage: eight
      cases (1990-1995).
AB  - Thrombocytopenia was documented in eight of 11 dogs with anticoagulant
      rodenticide-induced hemorrhage. Thrombocytopenia was transient and generally mild
      to-moderate, but it became marked (i.e., less than 30,000 platelets/microl) in
      two cases. Petechial hemorrhages were not noted in any case. There was no
      relationship between hematocrit and platelet count. Platelet count changes in
      response to treatment with fresh-frozen plasma and isotonic electrolyte solutions
      were variable. Anticoagulant rodenticide toxicity should be included as a
      differential diagnosis for dogs with hemorrhage accompanied by mild-to-moderate
      thrombocytopenia.

PMID- 9278118
TI  - Urethral obstruction in a dog: an unusual presentation of T-cell lymphoma.
AB  - A six-year-old, neutered male golden retriever was presented for evaluation of
      stranguria. Upon physical examination, the dog was thin and actively was
      straining to urinate. A large, firm bladder was palpated. Urethral pressure
      profilometry was indicative of a focal, nondistensible lesion in the midurethra
      which was confirmed with a positive contrast urethrogram. Ultrasonographically, a
      well-marginated tubular mass was visualized midurethra, and a region of small
      bowel was noted to have an annular mural thickening with corrugations of the
      mucosal surface. The abnormal areas were aspirated percutaneously, and lymphoma
      was diagnosed upon cytological examination of the aspirated material. At
      necropsy, a diagnosis of diffuse T-cell lymphoma was confirmed.

PMID- 9278119
TI  - Effect of infusion regime on doxorubicin pharmacokinetics in the cat.
AB  - In the pharmacokinetic evaluation of a single doxorubicin dose calculated by body
      surface area (25 mg/m2) or body weight (1 mg/kg body weight) and given
      intravenously as a 10-, 15-, or 20-minute infusion, the rate of doxorubicin
      infusion (mg per minute per m2 or mg per minute per kg) correlated positively
      with clearance and the distribution rate constant alpha, and it inversely
      correlated with area under the plasma concentration versus time curve (AUC).
      These findings suggest that a slower infusion rate results in a greater AUC and
      longer distribution phase than a faster infusion rate and indicates the
      importance of normalizing dosage regimes by infusion rate rather than by infusion
      duration when considering dose-response phenomena in veterinary patients.

PMID- 9278120
TI  - Splenic hemangiosarcoma and concurrent ossifying gastric adenocarcinoma in a dog.
AB  - An eight-year-old, spayed female, mixed Airedale terrier was presented for
      chronic vomiting and weight loss. Although emaciated, the dog had a pendulous
      abdomen with a palpable, left-sided, cranial abdominal mass. Diagnostic imaging
      confirmed a mass effect associated with both the spleen and stomach; it was
      unclear whether one mass or two was present. Necropsy confirmed the presence of
      two unrelated malignant abdominal neoplasms: a splenic hemangiosarcoma and an
      ossifying gastric adenocarcinoma.

PMID- 9278122
TI  - Arthroscopic examination and treatment of osteochondritis dissecans of the
      femoral condyle of six dogs.
AB  - Arthroscopy was used to diagnose and treat osteochondritis dissecans (OCD) of the
      femoral condyle in six dogs. Bilateral lesions were seen in two dogs. The medial
      condyle was affected in five stifles, and the lateral condyle was affected in
      three stifles. Subchondral bone defects were identified on radiographs in six of
      eight affected stifles. Resolution of the lameness associated with the
      arthroscopic procedure occurred one-to-14 days (mean, three days) following
      arthroscopy. Lameness resolved completely in four cases within two weeks and in
      one case six weeks following arthroscopy. Mild lameness persisted in one case.
      Arthroscopy is an effective means of diagnosis and treatment of OCD of the
      femoral condyle, and it is associated with minimal postoperative morbidity when
      compared to arthrotomy.

PMID- 9278121
TI  - Evaluation of the sedative and cardiorespiratory effects of medetomidine,
      medetomidine-butorphanol, medetomidine-ketamine, and medetomidine-butorphanol
      ketamine in ferrets.
AB  - Ten ferrets were used in a crossover study to determine the anesthetic effects of
      intramuscular (I.M.) medetomidine (80 microg/kg body weight), medetomidine (80
      microg/kg body weight)-butorphanol (0.1 mg/kg body weight), medetomidine (80
      microg/kg body weight)-ketamine (5 mg/kg body weight), and medetomidine (80
      microg/kg body weight)-butorphanol (0.1 mg/kg body weight)-ketamine (5 mg/kg body
      weight). All ferrets assumed lateral recumbency within four minutes and remained
      dorsally recumbent for 100 minutes, until atipamezole (400 microg/kg body weight,
      I.M.) administration. All four anesthetic combinations were effective for
      chemical restraint, with the most respiratory depression occurring in the
      medetomidine-butorphanol-ketamine group. The addition of butorphanol or ketamine
      to medetomidine significantly increased the duration of analgesia. The addition
      of ketamine to medetomidine-butorphanol expedited endotracheal intubation.

PMID- 9278123
TI  - Thoracolumbar intervertebral disk disease in large, nonchondrodystrophic dogs: a
      retrospective study.
AB  - Medical records of 62 large, nonchondrodystrophic dogs diagnosed with
      thoracolumbar intervertebral disk disease between March 1986 and February 1996
      were reviewed. Fifty-seven (92%), primarily mixed-breed dogs (mean age, 6.6
      years) had Hansen type I disease. Fifty-eight percent had acute onset. The
      interspace between the first (L1) and second (L2) lumbar vertebrae was affected
      most commonly. The outcomes of the 48 dogs available for follow-up after
      undergoing laminectomies were evaluated. Surgical success rate and mean time to
      walking for nonambulatory dogs with deep pain perception was 90% and seven weeks,
      respectively. Thirty-nine percent had residual deficits. Following surgery, 12%
      had recurrence of disk protrusion/extrusion at a different site.

PMID- 9278124
TI  - Steroid-responsive, cervical, pyogranulomatous pachymeningitis in a dog.
AB  - Syndromes of steroid-responsive meningitis have been described in the dog and
      typically are characterized by neutrophilic pleocytosis and an elevated protein
      concentration of the cerebrospinal fluid. In a minority of cases, histopathology
      has demonstrated suppurative leptomeningeal (i.e., arachnoid and pia)
      inflammation. A case of compressive, cervical, pyogranulomatous inflammation of
      undetermined cause affecting the dura mater (i.e., pachymeningitis), accompanied
      by fever and hyperpathia, is presented. The pachymeningitis ultimately regressed
      with long-term immunosuppressive therapy. This case shares features with
      hypertrophic spinal pachymeningitis of humans, an uncommon, frequently
      idiopathic, chronic inflammatory disorder causing dural hypertrophy,
      radiculopathy, and spinal cord compression.

PMID- 9278125
TI  - Implementation of the WHO Global Strategy for Occupational Health for All. Plan
      of action: covering the specific period 1996-2001. Part I.
AB  - The WHO Executive Board, at its Ninety-Seventh Session, in January 1996,
      recognized the vital role of occupational health in sustainable development and
      public health as a whole, endorsed the WHO Global Strategy for Occupational
      Health for All (Resolution EB97.R6). In May 1996, the World Health Assembly
      discussed occupational health and adopted a resolution on the WHO Global Strategy
      for Occupational Health for All (WHA49.12), requesting the Director-General to
      promote the implementation of the Global Strategy for Occupational Health for All
      within the framework of the Ninth General Programme of Work. Member States were
      urged to devise national programmes on occupational health for all, based on the
      global strategy, with special attention to pull occupational health services for
      the working population, including migrant workers, workers in small enterprises,
      in the informal sector, and for other occupational groups at high risk and with
      special needs, including children at work. Therefore, the draft Plan of Action
      for the Implementation of the WHO Global Strategy for Occupational Health for All
      has been prepared. The description of all 10 objectives of the global strategy,
      at both the international and national levels, are merged with appropriate
      activities of WHO and other contributing organizations. The Global Network of the
      WHO Collaborating Centres in Occupational Health is given a special role in the
      implementation of the global strategy.

PMID- 9278126
TI  - An analysis of the meaning of some concepts related to health.
AB  - From the logical point of view health is a certain condition (state) of the human
      organism, i.e. a set of the organism's attributes. The components of an abstract
      (general) notion of health, i.e. its features, are classes of phenomena which may
      be ascribed to a given individual. The concrete notion of health (condition of
      health) of a given individual embraces particular realisations of the features,
      i.e. values or properties of the organism. The health attributes are one-argument
      relations as well as two- or multi-argument ones. The health features and
      properties are either external (subjectively and/or intersubjectively observable)
      or internal (characterizing the internal parts of the organism). The distinction
      of normal (positive) and abnormal (negative, pathological) external and internal
      health properties is based mainly on systemic, statistic and subjective criteria.
      According to the everyday usage, the sets of external negative properties are
      illnesses, while the sets of internal negative ones that provoke (actually or
      potentially) and illness correspond to diseases or pathological entities.

PMID- 9278127
TI  - Kienbock's disease. II. Risk factors, diagnosis, and ergonomic interventions.
AB  - The term CTD has been used to refer to those musculoskeletal impairments that
      appear to be work-related and tend to be chronic. Upper extremity CTD are
      categorized in three major groups: tendon disorders, neurovascular disorders, and
      nerve. Kienbock's disease, on the other hand, has been documented in the
      workplace and has a similar etiology, but due to current anatomic classifications
      cannot be considered a CTD. With this in mind, the present article reviews risk
      factors, diagnosis, and treatment, with the purpose of providing physicians,
      engineers, and designers with information to reduce the risk of workers
      developing this potentially debilitating disease. Furthermore, additional support
      will be accumulated and combined with Part I of this article with the intent of
      introducing into the literature a new category of upper extremity CTD: Bone
      Disorders.

PMID- 9278129
TI  - Poison Information Service of the Nofer Institute of Occupational Medicine in
      Lodz. Types of toxicological inquiries 1991-1994.
AB  - The National Poison Information Centre and the physicians of the Clinic of Acute
      Poisonings, the Nofer Institute of Occupational Medicine in Lodz, provide
      telephone toxicological information to the medical professions and the general
      public. The most frequently offered advice was for drugs, pesticides, solvents,
      corrosives and mixtures. The most frequent drug inquiries concerned
      tranquillizers, hypnotic and psychotropic drugs. Advice to the public most
      frequently involved the toxic action and composition of various agents. At
      present, much effort is devoted at the National Poison Information Centre to
      develop a system of toxicologic information for the general public.

PMID- 9278128
TI  - System for analysing sickness absenteeism in Poland.
AB  - The National System of Sickness Absenteeism Statistics has been functioning in
      Poland since 1977, as the part of the national health statistics. The system is
      based on a 15-percent random sample of copies of certificates of temporary
      incapacity for work issued by all health care units and authorised private
      medical practitioners. A certificate of temporary incapacity for work is received
      by every insured employee who is compelled to stop working due to sickness,
      accident, or due to the necessity to care for a sick member of his/her family.
      The certificate is required on the first day of sickness. Analyses of disease-
      and accident-related sickness absenteeism carried out each year in Poland within
      the statistical system lead to the main conclusions: 1. Diseases of the
      musculoskeletal and peripheral nervous systems accounting, when combined, for 1/3
      of the total sickness absenteeism, are a major health problem of the working
      population in Poland. During the past five years, incapacity for work caused by
      these diseases in males increased 2.5 times. 2. Circulatory diseases, and
      arterial hypertension and ischaemic heart disease in particular (41% and 27% of
      sickness days, respectively), create an essential health problem among males at
      productive age, especially, in the 40 and older age group. Absenteeism due to
      these diseases has increased in males more than two times.

PMID- 9278130
TI  - Sources of poisoning exposures in children during 1990-1995. An analysis of the
      National Poison Information Centre files.
AB  - Information protocols on the causes of acute poisoning exposures with chemicals
      in children up to 14 years old collected during 1990-95 at the National Poison
      Information Centre have been analyzed. Approximately 96% of intoxication were
      accidental, 44% of patients were poisoned with drugs, 22% with household products
      and 14% with pesticides. Almost 25% of drug poisonings were due to sedative and
      to psychotropic drugs, and 17% to drug mixtures. The frequency of mushrooms and
      plants poisonings were low - 6%. In Poland there are practically no acute
      poisoning departments which treat children (actually, there is only one Poison
      Unit in Krakow at Polish-American Children's Hospital), and thus these patients
      are treated in paediatric wards and paediatric hospitals, so complete data on the
      poisonings in children from over the whole territory of Poland are not available.
      However, we believe that the frequency of causes of children's intoxication in
      our country is properly reflected in our material. This allows us to draw
      conclusions of the prevention of poisoning in this age group.

PMID- 9278131
TI  - Concentration of metals, ceruloplasmin, metallothionein and the activity of N
      acetyl-beta-D-glucosaminidase and gamma-glutamyltransferase in pregnant women who
      smoke and in those environmentally exposed to tobacco smoke and in their infants.
      Part I.
AB  - Concentrations of metals (Zn, Cu, Se, Cd), metallotionein (MT) and ceruloplasmin
      (Cp), and the activity of N-acetyl-beta-D-glucosaminidase (NAG) and gamma
      glutamyltransferase (gammaGT) in pregnant women who smoke and in passive smokers
      as well as in their newborns were measured. In smoking women a many-fold increase
      in cotinine concentrations in maternal and infant urine, amniotic fluid, placenta
      and milk was found as compared to passive smokers. Smoking lowered serum Se
      concentration in mothers and infants, increased serum ceruloplasmin in mothers
      and decreased serum Cu concentration in infants. Serum Zn level in infants was
      higher than in mothers, and smoking furthered its increase. Statistically
      significant increase in concentrations of Cd in placenta, amniotic fluid and
      milk, of Cu in placentae and amniotic fluid and of Zn in placenta and milk was
      revealed. Higher concentrations of metals were accompanied by an elevated MT
      level in placenta and amniotic fluid. In smoking women a significant increase in
      NAG activity in urine, amniotic fluid and milk, increase in gammaGT activity in
      urine and amniotic fluid and decrease in gammaGT activity in milk and placenta
      were observed. There was high, positive correlation between MT/NAG and MT/gammaGT
      in amniotic fluid of passive and active smokers, while similar correlation in
      milk was indicated only in the group of active smokers. The biochemical
      parameters analysed proved their usefulness in the evaluation of effects of
      exposure to cigarette smoke on pregnant woman and her fetus.

PMID- 9278132
TI  - Chemical-induced changes in intracellular redox state and in apoptosis.
AB  - Necrosis and apoptosis are two ways by which cells die. A major concept of
      apoptosis is that it is a controlled process. From this concept it follows that
      cells contain a molecule or molecules which under specific, regulated
      circumstances mediate cell death. Recent data confirm that oxygen free radicals
      can be mediators of apoptosis. Chemicals could induce apoptosis due to reactive
      oxygen species production and changes in the intracellular redox state.
      Therefore, a complete understanding of the processes involved in apoptosis, and
      mechanisms of its manipulation, could provide novel strategies to the control of
      xenobiotic toxicity and give an impetus to design new therapeutic interventions.

PMID- 9278133
TI  - Retardation of the age-related increase in spontaneous cortical spike-wave
      discharges (SWD) in rats after a 28-day inhalation (SWD) in rats after a 28-day
      inhalation exposure to an industrial solvent, pseudocumene (1,2,4
      trimethylbenzene).
AB  - It has been hypothesized that exposure to neurotoxins may hasten the process of
      brain ageing. Volatile hydrocarbons are in common use as solvents and their
      neurotoxic properties are acknowledged. In the rat, the age-related
      neurodegenerative changes in the brain develop together with an increased
      occurrence of bursts of spontaneous spike-wave discharges (SWD) in the neocortex.
      Therefore, the number and/or duration of SWD bursts may serve as an index
      allowing to distinguish between young and old brains (7). Measuring the SWD
      activity after exposure may thus reveal the effect of the studied neurotoxicant
      on brain ageing. Pseudocumene (1,2,4-trimethylbenzene, TMB), is a component of
      industrial solvent mixtures. The present study investigated the effect of a 4
      week (6h/day, 5 days/week) inhalation exposure to TMB at concentrations of 0, 25,
      100 or 250 ppm on the occurrence of SWD bursts. EEG recordings were performed
      before and one day, 30 days and 4 months after exposure. In rats exposed to TMB
      at 0 and 25 ppm, the level of the SWD activity increased progressively after
      exposure. In rats exposed to TMB at 100 or 250 ppm, the SWD activity did not
      increase during the post-exposure period or even dropped below the pre-exposure
      level. This result indicates that the persistent changes in the rat central
      nervous system (CNS), following the exposure to TMB, differ in some respects from
      those which develop in the course of normal ageing.

PMID- 9278135
TI  - The Arolla Workshop--some of its history.

PMID- 9278134
TI  - American Industrial Hygiene Conference and Exposition (Washington, USA, 18-24 May
      1996).

PMID- 9278136
TI  - KRAB zinc finger proteins and nuclear receptors: a possible cross-talk.

PMID- 9278137
TI  - Hedgehog and its patched-smoothened receptor complex: a novel signalling
      mechanism at the cell surface.
AB  - Pattern formation and morphogenesis depend on the careful execution of complex
      genetic programs, which are conserved in multicellular organisms. An important
      signal in some of these programs in Drosophila and vertebrates is the secreted
      Hedgehog (Hh) protein, which primarily functions as an inducer of morphogenetic
      signals. The Hh signal plays a decisive role in such critical developmental
      processes as neurulation and somite and limb formation. The Hh signalling pathway
      exhibits a novel mechanism of signal reception and transduction. In the absence
      of the Hh signal, the membrane protein Patched (Ptc) represses the constitutive
      signalling activity of a second membrane protein, Smoothened (Smo), by virtue of
      its ability to form a Ptc-Smo complex. Hence, mutations within the ptc gene that
      result in the failure of Ptc to inhibit Smo lead to constitutive activity of the
      Hh signalling pathway and to cancer, such as basal cell carcinoma. For activation
      of Hh-target genes, the N-terminal signalling domain of Hh binds to the Ptc-Smo
      receptor complex to activate two parallel signalling pathways. Furthermore, Hh
      limits its own range of action by impeding its diffusion through (i) covalent
      linkage of its N-terminal signalling moiety to cholesterol, mediated by the
      cholesterol transferase activity of its C-terminal moiety, and (ii) induction of,
      and sequestration by, its antagonist, Ptc.

PMID- 9278138
TI  - Telomere length regulation: getting the measure of chromosome ends.
AB  - Telomeres, the protein-DNA complexes that comprise the ends of linear eukaryotic
      chromosomes, serve to protect the chromosome ends and allow their complete
      replication. Telomeres also appear to play an essential role in chromosome
      segregation. In most organisms telomeric DNA consists of a series of short
      repeats that are variable in length, but regulated at a fixed average value in
      the germline. The possible involvement of telomere repeat shortening in aging and
      carcinogenesis has recently attracted attention to the more basic question of how
      telomere length is sensed and regulated by the cell. Telomere length in the
      budding yeast Saccharomyces cerevisiae has been known for over a decade now to be
      under complex genetic control, and this organism has provided a useful model
      system to address basic mechanistic questions. This review focuses on recent
      studies in yeast which indicate that the double-strand telomere-repeat binding
      protein Rap1 may play an important role in a negative-feedback mechanism that
      senses and controls the length of the telomere repeats. Although the same carboxy
      terminal domain of Rap1p is involved in both telomere length regulation and
      telomeric silencing (telomere position effect), it appears that these two
      functions are mediated by separate sets of Rap1p-interacting proteins. Results
      from other systems suggest that negative regulation of telomere elongation by a
      double-stranded telomere-repeat binding protein may be a highly conserved
      strategy for telomere length control.

PMID- 9278139
TI  - The role of DNA conformation in transcriptional initiation and activation in
      Escherichia coli.
AB  - Transcription activation in prokaryotes relies on a multitude of molecular
      mechanisms. Many of them use DNA bending or other deformations of the DNA to
      control the rate of transcription initiation. All steps of initiation involve a
      particular transconformation reaction of the DNA and can be controlled
      individually by activators. This review discusses the thermodynamic and kinetic
      basis of transcription initiation and illustrates the strategies used by
      activators. Particular emphasis is given to mechanisms that necessitate DNA
      bending by the activator.

PMID- 9278140
TI  - Oxygen(es) and the hypoxia-inducible factor-1.
AB  - The hypoxia-inducible factor-1 (HIF-1) is a basic-helix-loop-helix (bHLH)
      heterodimeric transcription factor activated by reductions in oxygen
      concentration (hypoxia). Activated HIF-1 upregulates expression of genes involved
      in the adaptation of higher organisms to hypoxic conditions, caused by e.g. high
      altitude, anemia, wound healing or during development. Examples of these oxy
      genes include erythropoietin, a hormone regulating erythropoiesis and hence the
      oxygen transport capacity, and vascular endothelial growth factor, a potent
      inducer of angiogenesis leading to increased blood capillary density. The HIF-1
      heterodimer is composed of a HIF-1alpha and an ARNT subunit, both belonging to
      the explosively growing PAS subfamily of bHLH transcription factors. Closely
      related, but differentially expressed, factors have recently been cloned, at
      least one of which can also be activated by hypoxia. In this review, we present a
      survey of the bH LH-PAS family as well as of the genes regulated by HIF-1, and we
      summarize our current knowledge on the oxygen-dependent activation of this
      fascinating transcription factor.

PMID- 9278141
TI  - 2-Oxo acid dehydrogenase multienzyme complexes. The central role of the lipoyl
      domain.
AB  - 2-Oxo acid dehydrogenase complexes are composed of multiple copies of at least
      three different enzymes, 2-oxo acid dehydrogenase, dihydrolipoyl acyltransferase
      and dihydrolipoamide dehydrogenase. The acyltransferase component harbours all
      properties required for multienzyme catalysis: it forms a large multimeric core,
      it contains binding sites for the peripheral components, the acyltransferase
      active site and mobile substrate carrying lipoyl domains that couple the active
      sites. In the past years these complexes have disclosed many of their secrets,
      providing currently a wealth of information on macromolecular structure, assembly
      and symmetry, active-site coupling, conformational mobility, substrate
      specificity and metabolic regulation. In this review we will discuss developments
      concerning the structural and mechanistic features of the 2-oxo acid
      dehydrogenase complexes, with special emphasis on the structure and role of the
      lipoyl domains in the complex.

PMID- 9278142
TI  - Aims and limitations in the use of antipeptide antibodies in molecular biology.
AB  - Antibodies to peptides obtained by synthesis and, to a much lesser extent,
      prepared by enzymatic digestion of proteins, have been widely used in the last
      ten years in a variety of immunochemical and biological investigations. There are
      however several limitations in the correct utilization of such reagents. In fact,
      in spite of their 'predetermined specificity', antipeptide antibodies often fail
      to discriminate related molecules, and their reactivity with native proteins may
      be scarce or even absent, even if the peptide has been selected from surface
      regions of the protein. Our critical point of view, concerning two main aspects
      of antipeptide antibody features, i.e. specificity and reactivity, will be
      presented here, as confronted with information from the available literature. We
      have selected a restricted number of references among hundreds of publications
      dealing with antipeptide antibodies: for sure we neglected outstanding papers on
      the subject, and we apologize in advance.

PMID- 9278143
TI  - Energy- and temperature-dependent in vitro export of RNA from synthetic nuclei.
AB  - We describe a novel assay for the study of RNA export from the nucleus in vitro.
      Nuclei are assembled in Xenopus egg extract on paramagnetic beads coated with DNA
      containing a specific template for transcription. T7 RNA polymerase, to which a
      nuclear localisation signal is attached, is added to the nuclei, and after its
      import into the assembled nuclei, transcription is allowed to proceed. The use of
      radioactive NTPs coupled with the possibility to purify the nuclei on a magnet
      and thus rapidly change the extract in which the nuclei are incubated allows
      pulse-chase labelling experiments. Using these protocols we show that U1 snRNA
      derived templates are transcribed inside the synthetic nuclei, and that the
      transcripts leave the intact nuclei in a time-, temperature- and energy-dependent
      way. This offers the possibility of a biochemical approach to the dissection of
      RNA export.

PMID- 9278144
TI  - PPAR alpha structure-function relationships derived from species-specific
      differences in responsiveness to hypolipidemic agents.
AB  - The nuclear receptor PPAR alpha is a key regulatory transcription factor in lipid
      homeostasis, some liver detoxification processes and the control of inflammation.
      Recent findings suggest that many hypolipidemic drugs and anti-inflammatory
      agents can potentially act by binding to PPAR alpha and inducing its activity.
      Here, we identify some structure-function relationships in PPAR alpha, by using
      the species-specific responsiveness to the two hypolipidemic agents, Wy 14,643
      and 5,8,11,14-eicosatetraynoic acid (ETYA). We first show that the species
      specific differences are mediated primarily via the ligand binding domain of the
      receptor and that these two drugs are indeed ligands of PPAR alpha. By
      mutagenesis analyses we identify amino acid residues in the ligand binding
      domains of Xenopus, mouse and human PPAR alpha, that confer preferential
      responsiveness to ETYA and Wy 14,643. These findings will aid in the development
      of new synthetic PPAR alpha ligands as effective therapeutics for lipid-related
      diseases and inflammatory disorders.

PMID- 9278145
TI  - Cooperative interactions of AP-1 and basic helix-loop-helix transcription factors
      regulate T1 gene expression.
AB  - The T1 gene is a murine, delayed early serum-responsive gene that encodes
      glycoproteins of the interleukin-1 receptor (IL-1R) family. Transcription of the
      T1 gene leads to production of two mRNAs that encode a transmembrane protein,
      which is highly similar to the type-1 IL-1R, and a secreted protein, which
      consists solely of the extracellular part. Fibroblasts, in contrast to mast
      cells, express predominantly the shorter form of the protein, and several
      mitogens cause strong, transient induction of the T1 gene in these cells. Here we
      describe the identification of a 148 bp enhancer element that is positioned 3.6
      kb upstream of the transcription initiation site. A TPA-responsive element (TRE)
      and three identical E-boxes are located within this sequence. Introduced point
      mutations confirmed the necessity of these sites for full T1 promoter activity.
      The TRE and the distal E-box are absolutely indispensable for promoter function,
      whereas the two proximal E-boxes contribute less to promoter strength. In vitro
      the three E-boxes are bound by different protein complexes.

PMID- 9278146
TI  - Silencing of RNA polymerases II and III-dependent transcription by the KRAB
      protein domain of KOX1, a Kruppel-type zinc finger factor.
AB  - The so-called KRAB domain, which is present in about one third of the vertebrate
      Kruppel-type zinc finger factors, has previously been shown to inhibit
      transcription in cis when tethered to promoter regions. Here we analyze this
      effect with fusions of the KRAB domain derived from KOX1/ZNF10 zinc finger
      protein to the heterologous DNA binding domains of both LexA and GAL4 factors. In
      transfected human cells, repression of reporter gene transcription is observed
      not only from proximal promoter positions, but also when KRAB is tethered to DNA
      at a remote position more than 1.8 kb downstream of the initiation site of
      transcription. Furthermore, KRAB-mediated silencing over short and long distances
      is not restricted to RNA polymerase II, since transcription by RNA polymerase III
      is also repressed. However, transcription by RNA polymerase I and by phage T7 RNA
      polymerase in mammalian cells are not significantly influenced by the KRAB
      domain. These latter results may indicate that repression by the KRAB domain, at
      least under our assay conditions, involves specific inhibition of some
      component(s) of RNA polymerase II and III transcription, rather than inducing
      some gross physical alteration of template chromatin structure.

PMID- 9278147
TI  - The PGK-TIM fusion protein from Thermotoga maritima and its constituent parts are
      intrinsically stable and fold independently.
AB  - In the hyperthermophilic bacterium Thermotoga maritima, the two glycolytic
      enzymes phosphoglycerate kinase (PGK) and triosephosphate isomerase (TIM) are
      covalently connected forming a tetrameric single-chain PGK-TIM fusion protein. A
      frameshift allows the translation of PGK alone, whereas TIM activity exclusively
      resides in the fusion protein (Schurig et al., 1995). Cloning the pgk-tim gene
      from Thermotoga maritima in Escherichia coli, yields monomeric PGK and tetrameric
      PGK-TIM fusion protein as authentic recombinant proteins (Beaucamp et al., 1995).
      Both exhibit high intrinsic stability. The thermal transitions at approximately
      80 degrees C are irreversible, rendering determination of thermodynamic data
      impossible. The half-concentrations, (cGdmCl)1/2, of the guanidinium-chloride
      induced unfolding transitions are 3.0 and 3.9 M GdmCl for PGK and the PGK-TIM
      fusion protein, respectively. Monitoring denaturation by activity, fluorescence
      emission and circular dichroism, deactivation and unfolding of the two-domain PGK
      is found to precede the transitions of the TIM domain. With increasing
      temperature, (cGdmCl)1/2 is shifted to lower denaturant concentrations; at the
      same time, the transitions change from bimodal to unimodal. As indicated by the
      incomplete reversibility of the deactivation/unfolding/dissociation transitions,
      misfolding, as well as wrong domain interactions seem to interfere with the
      correct folding and association of the bienzyme complex.

PMID- 9278148
TI  - Expression in Escherichia coli, purification, and spectroscopic characterization
      of two mutant Bet v 1 proteins.
AB  - Bet v 1 is the major birch pollen allergen. A highly efficient expression and
      purification scheme for mutant forms of this protein was developed on the basis
      of the pET expression system in order to provide the high quantities of protein
      needed for spectroscopic and structural work. Bet v 1 (M139L) protein could be
      purified at high yield (approx. 30 mg from 1 liter of LB medium) in a two-step
      procedure by the use of metal-affinity chromatography. Matrix assisted laser
      desorption ionisation mass spectroscopy, and size exclusion chromatography
      demonstrate the homogeneity and purity of the prepared protein. Spectroscopic
      methods were used to show that Bet v 1 (M139L) is structurally similar to wild
      type Bet v 1. Furthermore, we investigated the influence of the nature of amino
      acid 139 on the thermodynamic behaviour of the protein by replacing the leucine
      residue by alanine. While there appears to be no global structural effect of this
      mutation, the thermostability of Bet v 1 is greatly decreased.

PMID- 9278149
TI  - Dynamic structure of the sarcin/ricin domain in rat 28S ribosomal RNA
      investigated by hybridization with oligodeoxynucleotide.
AB  - In the static state of the ribosome, its S/R domain is not accessible to a probe
      of 1 4-mer oligodeoxyribonucleotide complementary to the region. However, during
      the in vitro translation process, the probe can specifically hybridize with the
      region in ribosome and inhibit translation. It appears that the S/R domain is
      well-protected when the ribosome is in the static state. This site is partially
      exposed at some stage(s) of translation. These results indicate that the S/R
      domain is not a simple single-strand, but a reversibly dynamic structure.

PMID- 9278150
TI  - Undersulfation of proteoheparan sulfate stimulates the expression of basic
      fibroblast growth factor and protein synthesis but suppresses replication of
      coronary smooth muscle cells.
AB  - Heparan sulfate proteoglycans are obligatory for receptor binding and mitogenic
      activity of the basic fibroblast growth factor (bFGF). In the present study the
      influence of undersulfated heparan sulfate on the expression of basic fibroblast
      growth factor and coronary smooth muscle cell (cSMC) proliferation was
      investigated. Chlorate, known to be an inhibitor of ATP-sulfurylase, was used as
      a tool to suppress sulfation of heparan sulfate. When cultured cSMC were treated
      with 10 mM sodium chlorate in sulfate-depleted medium, the cell number and
      [3H]thymidine incorporation decreased by 76% and 66% respectively, while the
      protein content per cell was doubled. At the same time the [35S]sulfate
      incorporation into cell-associated proteoglycans was reduced by 90%. The
      remaining minimal amount of available [35S]radioactivity was preferably
      incorporated into heparan sulfate. Under the same conditions the [6
      (3)H]glucosamine incorporation into glycosaminoglycans was not impaired. The
      chlorate-induced increase of cell protein content includes an overexpression of
      bFGF, which increased from 6-8 ng to 18-22 ng/mg cell protein. However, no
      changes in the distribution of bFGF between the intracellular and pericellular
      compartment could be observed. Cell cycle analysis by FACS revealed a G1 arrest
      of the cell cycle with increase of the G1/S ratio from 2.9 (control) to 6.1
      (chlorate) but the DNA content per cell corresponded to normal diploid cells both
      in control and chlorate-treated cells. The chlorate effect can be abolished by
      addition of 5 mM sodium sulfate to the cultures. Our results demonstrate an
      inverse association between the sulfation of heparan sulfate and the expression
      of bFGF. They suggest that chlorate blocks the cell cycle in the late G1-phage
      and that mitogenesis of cSMC requires fully sulfated cell-associated
      proteoheparan sulfate.

PMID- 9278151
TI  - Tyrosine nitration as a mechanism of selective inactivation of prostacyclin
      synthase by peroxynitrite.
AB  - Vascular tone critically depends on the endothelial release of nitric oxide and
      prostacyclin. Superoxide anions counteract these relaxations by trapping nitric
      oxide under formation of peroxynitrite. As we have recently reported,
      peroxynitrite is able to inhibit prostacyclin formation in aortic microsomes (Zou
      et al., 1996). Here we show that peroxynitrite also blocks purified prostacyclin
      synthase with an IC50 value of about 50 nM and with a similar sensitivity also
      inhibits the enzyme activity in the EaHy 926 endothelial cell line. Thromboxane
      synthase, having the same heme-thiolate (P450) structure and a closely-related
      mechanism was unaffected by peroxynitrite. Anti-nitrotyrosine antibodies reacted
      positive by a Western blot after treatment of the purified enzyme with 1 microM
      peroxynitrite. Tetranitromethane also inhibited the enzyme activity which, like
      the inhibition by peroxynitrite, could be partially prevented in the presence of
      the substrate analog U46619. The simultaneous generation of superoxide and nitric
      oxide proved to be as efficient as a bolus of peroxynitrite which supports a
      possible inactivation of prostacyclin synthase under in vivo conditions. This
      substantiates an often suggested crucial role of superoxide in the
      pathophysiology of the cardiovascular system.

PMID- 9278152
TI  - Recombinant wild-type and mutant complexes of ferredoxin and ferredoxin:NADP+
      reductase studied by isothermal titration calorimetry.
AB  - The interaction of spinach ferredoxin:NADP+ reductase (FNR) with ferredoxin (Fd)
      is driven by a favorable change of entropy and shows almost no change in
      enthalpy. The change in heat capacity between the free proteins and the complex
      is -0.47 +/- 0.1 kJ mol(-1) K(-1), a value indicating a relatively small surface
      area buried in the complex. A single proton is taken up from the environment when
      the ferredoxin:FNR complex forms. In the complex, the protonated residue(s) is
      (are) probably located in the vicinity of E92 of Fd because charge reversal in
      Fd(E92K) quenches protonation. Substitution of K88 by Q in FNR(K88Q) destabilizes
      the complex by a 7 kJ mol(-1) reduction in binding entropy, which indicates that
      dehydration of the complex interface contributes to stability.

PMID- 9278153
TI  - Recombinant pyruvate kinase type I from Escherichia coli: overproduction and
      revised C-terminus of the polypeptide.
AB  - The gene encoding pyruvate kinase type I (PKI) of Escherichia coli was amplified
      by PCR, cloned and sequenced. The gene product was overexpressed in E. coli,
      using an inducible T7 RNA polymerase-based expression system. The transformed
      cells contained sixtyfold the enzyme activity of the reference cells and enabled
      the purification of 30 mg of highly active PKI from 1 liter of culture. The gene
      sequence was determined and found to be different from the one previously
      reported, i.e., the T nucleotide at position 1351 was missing. This resulted in a
      downstream shift of the stop codon, thus the deduced polypeptide was 470 amino
      acids long instead of 462. In addition the twelve C-terminal amino acids of the
      former sequence were changed.

PMID- 9278154
TI  - There is no highly conserved embryonic stage in the vertebrates: implications for
      current theories of evolution and development.
AB  - Embryos of different species of vertebrate share a common organisation and often
      look similar. Adult differences among species become more apparent through
      divergence at later stages. Some authors have suggested that members of most or
      all vertebrate clades pass through a virtually identical, conserved stage. This
      idea was promoted by Haeckel, and has recently been revived in the context of
      claims regarding the universality of developmental mechanisms. Thus embryonic
      resemblance at the tailbud stage has been linked with a conserved pattern of
      developmental gene expression - the zootype. Haeckel's drawings of the external
      morphology of various vertebrates remain the most comprehensive comparative data
      purporting to show a conserved stage. However, their accuracy has been questioned
      and only a narrow range of species was illustrated. In view of the current
      widespread interest in evolutionary developmental biology, and especially in the
      conservation of developmental mechanisms, re-examination of the extent of
      variation in vertebrate embryos is long overdue. We present here the first review
      of the external morphology of tailbud embryos, illustrated with original
      specimens from a wide range of vertebrate groups. We find that embryos at the
      tailbud stage - thought to correspond to a conserved stage - show variations in
      form due to allometry, heterochrony, and differences in body plan and somite
      number. These variations foreshadow important differences in adult body form.
      Contrary to recent claims that all vertebrate embryos pass through a stage when
      they are the same size, we find a greater than 10-fold variation in greatest
      length at the tailbud stage. Our survey seriously undermines the credibility of
      Haeckel's drawings, which depict not a conserved stage for vertebrates, but a
      stylised amniote embryo. In fact, the taxonomic level of greatest resemblance
      among vertebrate embryos is below the subphylum. The wide variation in morphology
      among vertebrate embryos is difficult to reconcile with the idea of a
      phyogenetically-conserved tailbud stage, and suggests that at least some
      developmental mechanisms are not highly constrained by the zootype. Our study
      also highlights the dangers of drawing general conclusions about vertebrate
      development from studies of gene expression in a small number of laboratory
      species.

PMID- 9278155
TI  - Expression of p53 and hsp70 in relation to apoptosis during Meckel's cartilage
      development in the mouse.
AB  - The process of Meckel's cartilage development was examined with regard to
      expression of p53, a tumor suppressor gene product and hsp70, a stress protein
      (heat-shock protein), in association with the occurrence of programmed cell death
      (apoptosis). Balb C mice embryos from embryonic days E13, E14, E15, E16, E17, E18
      and 1- and 3-day-old pups were used. P53-positive cells were detected first at
      E15, and were found in the perichondrium of the distal part of Meckel's
      cartilage. During the degeneration process chondrocytes also became p53-positive.
      In contrast to p53, the expression of hsp70 was high and widespread in the early
      stages of development (E13-E15); however, it decreased with age, except for
      Meckel's cartilage, where hsp70 was found in the cytoplasm or nuclei of the
      hypertrophic cells. Apoptosis was first detected at E14-E15 in the perichondrium
      of the distal parts of Meckel's cartilage. The number of apoptotic bodies
      increased with age and the ongoing resorption of Meckel's cartilage. From the
      present study it can be concluded that expression of p53 and hsp70 varied during
      the development of Meckel's cartilage and that both proteins showed nuclear
      location in hypertrophic cells. No direct spatial or temporal correlation was
      observed between the expression of p53 and hsp70 and the occurrence of apoptotic
      bodies.

PMID- 9278156
TI  - Formation of an alternate lamellar pattern in the advanced cellular
      cementogenesis in human teeth.
AB  - The formation of an alternate lamellar pattern in the advanced stage of cellular
      cementogenesis in human molars was examined by light and electron microscopy. In
      longitudinal ultrathin sections, longitudinally oriented intrinsic fibril bundles
      appeared in close and parallel association with slender processes of
      cementoblasts on the cementum. Where transversely oriented intrinsic fibril
      bundles appeared, cementoblasts formed indentations to enclose the fibril
      bundles. Cytoplasmic fragments were also enclosed in the indentations. Scanning
      electron microscopy indicated that cementoblasts have developed two types of
      processes on their cementum-facing side - ridge- and finger-like. The
      cementoblasts formed groove-like compartments by ridge-like processes in
      cooperation with other cementoblasts. The compartments formed groups, and in each
      group the compartments were arranged in the same direction. The finger-like
      processes were arranged in parallel with the ridge-like processes in the
      compartments. These observations suggest that: (1) slender processes and
      cytoplasmic fragments are longitudinally and transversely cut finger-like
      processes, respectively; (2) the cellular indentations are transversely cut
      groove-like compartments; (3) the cementoblasts regulate the intrinsic fiber
      arrangement by the two types of processes; (4) the cementoblasts move the two
      types of processes synchronously and periodically to cause an alternate change in
      the intrinsic fiber arrangement. This dynamic sequence results in the alternate
      lamellar pattern of cellular cementum.

PMID- 9278157
TI  - Ciliogenesis in photoreceptor cells of the tree shrew retina.
AB  - Transmission electron microscopy of the retinal cones from several prenatal,
      young postnatal and adult tree shrews (Tupaia belangeri) reveals that the
      centrioles, from which the ciliary precursors of the outer segments grow out, are
      not transported into a pre-existing inner segment, but are positioned under the
      apical plasma membrane of cone precursor cells all through the inner segment
      formation. Ciliogenesis starts before or on embryonic day 20 and thus precedes
      initial formation of the inner segment by 20 days, which is half the gestation
      period. Thus, the maturation of the outer segment covers a considerably longer
      period than has been previously described. Published observations from other
      mammals can be interpreted as conforming with the situation in Tupaia. In other
      vertebrates, compared to mammals, marked heterochronies do occur. In Tupaia, the
      centrioles and the cilium are located close to the central longitudinal axis of
      the photoreceptor precursor cell from the 20-day-old embryo to the 5-day-old
      juvenile. In this position the microtubule apparatus originating from the
      centrioles should be most effective in transporting the mitochondria into the
      inner segment. In the 12-day-old tree shrew, when transport of the mitochondria
      into the inner segment has been completed, centrioles and cilium have shifted
      into an eccentric position and the light-collecting megamitochondria have
      approached the disks of the outer segment. This eccentric position is maintained
      in all later developmental stages. In certain of the retinal areas of the adult
      Tupaia, the connecting cilia of neighbouring cones are always positioned on the
      same side of the inner segments.

PMID- 9278158
TI  - Androgen-dependent mast cell degranulation in the Harderian gland of female
      Syrian hamsters: in vivo and organ culture evidence.
AB  - In previous articles we have reported the "disappearance" of Harderian gland mast
      cells (HGMC) after treatment with testosterone. In the present work we study: (a)
      if the apparent decrease in the number of mast cells caused by this androgen is
      real or is due to the fact that testosterone induces mast cell degranulation that
      avoids its recognition by toluidine blue staining; (b) if testosterone acts
      through its receptor directly on the Harderian gland (HG). In order to give an
      answer to the first question, we observed HG of female Syrian hamsters treated
      with testosterone under the electron microscope to find the possible degranulated
      mast cells not recognizable with the aid of the toluidine blue staining. We also
      studied in vivo and in vitro the effects of the beta-agonists isoproterenol and
      salbutamol, given that they increase cAMP and can therefore prevent degranulation
      of mast cells. Finally we have used cytocalasin B, which inhibits degranulation
      by blocking actin depolimerization. Both the beta-agonists and cytochalasin B
      were able to prevent the decrease of mast cells, as recognized by staining with
      toluidine blue after treatment with testosterone. Indeed, when observed under the
      electron microscope, abundant degranulated mast cells were found after treatment
      with testosterone. For solving the second issue we analyzed the effect of the
      antiandrogen cyproterone acetate in vivo and in vitro. Our results demonstrate
      that testosterone is able to induce degranulation of HGMC in the Syrian hamster
      Mesocricetus auratus and that this effect is achieved directly through its
      receptor on the Harderian gland.

PMID- 9278159
TI  - Retinotopic order in the optic nerve and superior colliculus during development
      of the retinocollicular projection in the wallaby (Macropus eugenii).
AB  - Retinotopic order of optic axons in the optic nerve and superior colliculus of
      the marsupial mammal, the wallaby (Macropus eugenii), has been examined and
      compared during development of the retinocollicular projection to investigate the
      role of order in the nerve in map formation. Small groups of axons from different
      retinal quadrants were labelled in vivo with a carbocyanine dye from just after
      axons first reached the colliculus to when the projection was mature. The
      distribution and branching patterns of axons and their arbors on the colliculus
      were assessed quantitatively during this period, as was the degree of order in
      the nerve. Initially, axons accumulated in coarse retinotopic order in the
      colliculus, with little branching and no sign of arborization to form terminal
      zones. Axons labelled from deposits covering a mean of 2.2% of the retina reached
      a mean collicular coverage of around 30% at 41-47 days, at which time they began
      arborizing in their retinotopically correct positions. By 55 days axons from all
      retinal quadrants had formed terminal zones in their retinotopically correct
      positions. Axons did not arborise in incorrect positions as has been reported in
      the rat. By 61-68 days coverage had decreased to around 10%. By 90-95 days only
      axons supplying terminal zones were present and terminal zones were smaller. In
      the nerve, axons showed a coarse and consistent order throughout development.
      This order was retinotopic only immediately behind the eye. Temporal and nasal
      axons occupied corresponding halves of the nerve along its course. Axons from
      dorsal and ventral retina shifted from dorsal and ventral positions in the nerve,
      respectively, to opposite sides of the nerve just before the chiasm. This would
      assist in positioning them in the appropriate lateral and medial optic tracts,
      respectively, in the positions they occupied as they approached the colliculus.
      However, the position in the nerve was not related to the ability to arborize in
      the correct collicular position. In particular, the increase in retinotopic order
      in the colliculus late in development was not accompanied by an increase in order
      in the nerve. Since the final organization in the colliculus shows greater order
      than is ever seen in the nerve, additional mechanisms must be involved in the
      maturation of the collicular map.

PMID- 9278161
TI  - Ultrastructure of different types of thymic epithelial cells in normal and
      cyclosporin-A-treated rats.
AB  - Transmission electron microscopy was used to study the ultrastructural features
      of thymic epithelial cells of intact and cyclosporin-A-treated adult male Wistar
      rats. The animals received a peroral daily dose of 30 mg of cyclosporin A per kg
      body weight for 21 consecutive days. On the basis of ultrastructural features,
      seven subsets of epithelial cells were distinguished within the intact rat
      thymus. Four subsets were predominantly situated in the cortex (type 4 - "dark"
      cells - occasionally penetrated into the medullar region) and three were
      positioned within the thymic medulla. All subsets of thymic epithelial cells were
      markedly changed after the application of cyclosporin A. The prominent
      enlargement of cytokeratin contents was registered in type 1 -
      "subcapsular/paraseptal/perivascular" - epithelial cells. At the same time these
      cells acquired the morpho-functional aspect of resting cells. All other subsets
      of cortical epithelial cells were enlarged (though in different ways) in
      comparison to the corresponding subsets of the control thymus, whereby their
      subcellular organization was suggestive of increased synthetic and secretory
      activity. The decrease in the number of epithelial cells, with the prevalence of
      phenotypically immature subsets, was evident within the residual islands of
      thymic medullary tissue.

PMID- 9278160
TI  - Expression of myosin VIIA during mouse embryogenesis.
AB  - The gene encoding myosin VIIA is responsible for the mouse shaker-1 phenotype,
      which consists of deafness and balance deficiency related to cochlear and
      vestibular neuroepithelial defects. In humans, a defective myosin VIIA gene is
      responsible for Usher syndrome type IB, which associates congenital deafness,
      vestibular dysfunction and retinitis pigmentosa. In an attempt to progress in the
      understanding of the function(s) of myosin VIIA, we studied the expression of the
      myosin VIIA gene during mouse embryonic development. Embryos from day 9 (E9) to
      E18 were analyzed by in situ hybridization and immunohistofluorescence. The
      myosin VIIA mRNA and protein were consistently detected in the same embryonic
      tissues throughout development. Myosin VIIA was first observed in the otic
      vesicle at E9, and later in a variety of tissues. The olfactory epithelium and
      the liver express it as early as E10. In the retinal pigment epithelium, choroid
      plexus, adrenal gland and tongue, expression begins at E12 and in the testis and
      the adenohypophysis at E13. In the small intestine, kidney and hair follicles of
      the vibrissae, expression of myosin VIIA starts only at E15. Myosin VIIA
      expression was observed only in epithelial cell types, most of which possess
      microvilli or cilia. Interestingly, myosin VIIA expression seems to be
      concomitant with the appearance of these structures in the epithelial cells,
      suggesting a role for this myosin in their morphogenesis. The cellular location
      of myosin VIIA within sensory hair cells and olfactory receptor neurons also
      argues for a role of this protein in the synaptic vesicle trafficking.

PMID- 9278162
TI  - Characterization of the gene for pyruvate,orthophosphate dikinase from rice, a C3
      plant, and a comparison of structure and expression between C3 and C4 genes for
      this protein.
AB  - To investigate the molecular changes that might have occurred in genes for
      pyruvate,orthophosphate dikinase (PPDK) during the evolution of C4 plants from C3
      plants, we isolated a full-length cDNA and the corresponding gene for a C4-like
      PPDK from rice, a C3 gramineous plant and compared their structures and promoter
      activities to those of the corresponding gene from maize, a C4 gramineous plant.
      As in maize, there are at least two ppdk genes in rice and one of them was very
      similar to the maize C4-type ppdk. The deduced amino acid sequence of the rice
      PPDK was 88% homologous to the maize C4-type PPDK in the mature peptide region
      and 56% homologous in the transit peptide region. The C4-like ppdk in rice
      contained 21 exons, which were interrupted by twenty introns, and the positions
      of the introns were essentially the same as those in the gene from maize, with
      the except in that the gene from rice had two extra introns. Such extra introns
      were also found in the C4-type ppdk from a dicot, Flaveria, at the same
      positions. These results strongly suggest that the two introns were present in an
      ancestral gene before the divergence of monocot and dicot plants. The C4-like
      ppdk in rice contained two functionally independent promoters had generated a
      larger transcript with the transit peptide region and a smaller transcript
      without this region. The unusual dual-promoter system for transcription has been
      conserved in the C4-type ppdk gene from maize, indicating that the dual-promoter
      system is a common feature of ppdk genes in both C3 and C4 plants. The patterns
      of expression of the two transcripts in rice were different: the larger
      transcript was expressed exclusively in green leaves at a low level whereas the
      smaller transcript was expressed in some reproductive organs at a high level.
      Essentially the same patterns of expression were observed in maize, but the level
      of expression of the larger transcript in maize green leaves was much higher than
      that in green leaves of rice. The promoter activities of the rice and maize genes
      for PPDK were examined directly in a transient expression assay in maize
      mesophyll protoplasts after electroporation with promoter::beta-glucuronidase
      chimeric genes. The rice promoter for the smaller transcript was very active in
      the protoplasts but the rice promoter for the larger transcript had relatively
      low activity. By contrast, both promoters of the maize gene had high activity.
      Taken together, these results demonstrate that the rice C4-like ppdk is very
      similar to the maize C4-type ppdk, not only in terms of primary structure but
      also in terms of the regulation of expression, with the exception that the
      strength of the maize promoter for the larger transcript is higher. The results
      strongly suggest that the genetic alterations required to give rise to the C4
      type ppdk gene were relatively limited.

PMID- 9278163
TI  - Do nonasterid holoparasitic flowering plants have plastid genomes?
AB  - Past work involving the plastid genome (plastome) of holoparasitic plants has
      been confined to Scrophulariaceae (or Orobanchaceae) which have truncated
      plastomes owing to loss of photosynthetic and other genes. Nonasterid
      holoparasites from Balanophoraceae (Corynaea), Hydnoraceae (Hydnora) and
      Cytinaceae (Cytinus) were tested for the presence of plastid genes and a
      plastome. Using PCR, plastid 16S rDNA was successfully amplified and sequenced
      from the above three holoparasites. The sequence of Cytinus showed 121 single
      base substitutions relative to Nicotiana (8% of the molecule) whereas higher
      sequence divergence was observed in Hydnora and Corynaea (287 and 513 changes,
      respectively). Secondary structural models for these 16S rRNAs show that most
      changes are compensatory, thus suggesting they are functional. Probes constructed
      for 16S rDNA and for four plastid-encoded ribosomal protein genes (rps2, rps4,
      rps7 and rpl 16) were used in Southern blots of digested genomic DNA from the
      three holoparasites. Positive hybridizations were obtained using each of the five
      probes only for Cytinus. For Smal digests, all plastid gene probes hybridized to
      a common fragment ca. 20 kb in length in this species. Taken together, these data
      provide preliminary evidence suggestive of the retention of highly diverged and
      truncated plastid genome in Cytinus. The greater sequence divergence for 16S rDNA
      and the negative hybridization results for Hydnora and Corynaea suggests two
      possibilities: the loss of typically conserved elements of their plastomes or the
      complete absence of a plastome.

PMID- 9278164
TI  - Structural analyses of plastid-derived 16S rRNAs in holoparasitic angiosperms.
AB  - Higher-order structures have been constructed for plastid-encoded small-subunit
      (SSU, 16S), rRNAs from representatives of seven nonphotosynthetic holoparasitic
      angiosperm families: Apodanthaceae, Cynomoriaceae, Cytinaceae, Balanophoraceae,
      Hydnoraceae, Mitrastemonaceae, and Rafflesiaceae. Whereas most pairwise
      comparisons among angiosperms differ by 2-3% in substitutions, the 16S rRNAs of
      the holoparasites show an increasingly greater number of mutations: Cynomorium
      (7.3%), Cytinus (8.0%), Bdallophyton (12.7%), Mitrastema (14.9%), Hydnora
      (19.4%), Pilostyles (30.4%) and Corynaea (35.9%). Despite this high level of
      sequence variation, SSU structures constructed for all species except Pilostyles
      possess the typical complement of 50 helices (that contain numerous compensatory
      mutations) thereby providing indirect evidence supporting their functionality.
      Pilostyles, likely with the most unusual plastid 16S rRNA yet documented, lacks
      four major helices and contains lengthy insertions for four others. Sequences of
      products generated via RT-PCR show that these structural modifications are
      present on a mature (transcribed) rRNA. The trend toward increasing numbers of
      base substitutions in the holoparasites is accompanied by a marked increase in
      A+U content of the rRNA. This 'A/T drift' phenomenon of rDNA is especially
      apparent in Corynaea whose SSU rDNA sequence is 72% A+T. A comparison of Cytinus
      to tobacco showed that substitution rates appear to be dependent upon the
      composition of neighboring bases. Transversions represented 26% of the mutations
      when flanking bases were G or C whereas transversions increased to 36% when the
      flanking bases were A to T. The underlying molecular mechanism associated with
      these high substitution rates is presently unknown, however, relaxation of
      selection pressure on ribosome function resulting in altered DNA replication
      and/or repair systems may be involved.

PMID- 9278165
TI  - A model for the evolution of polyubiquitin genes from the study of Arabidopsis
      thaliana ecotypes.
AB  - Polyubiquitin genes encode the highly conserved 76-amino acid protein ubiquitin
      that is covalently attached to substrate proteins targeting most for degradation.
      Polyubiquitin genes are characterized by the presence of tandem repeats of the
      228 bp that encode a ubiquitin monomer. Five polyubiquitin genes UBQ3, UBQ4,
      UBQ10, UBQ11, and UBQ14, previously isolated from Arabidopsis thaliana ecotype
      Columbia [10] encode identical mature ubiquitin proteins, but differ in
      synonymous substitutions, nature of amino acids terminating the open reading
      frame, and in the number of ubiquitin repeats. The presence of these five genes
      in nine other Arabidopsis ecotypes was verified by polymerase chain reaction
      (PCR). Size differences in UBQ3 and UBQ11 amplified products from several
      ecotypes were observed, suggesting that alleles differ in ubiquitin repeat
      number. DNA sequence of UBQ11 alleles from each size class (ecotypes Be-0, Ler.
      and Rld-0) verified that PCR product size differences resulted from changes in
      the number of ubiquitin repeats. Nucleotide sequence between two UBQ11 alleles
      containing the same number of repeats was identical. Transcript size differences
      for UBQ3 and UBQ11 mRNAs between ecotypes Columbia and Landsberg indicated that
      repeat number changes did not inactivate these genes. Nucleotide sequence
      comparisons between UBQ11 repeats from different ecotypes suggest that first
      repeats are related to each other and last repeats are related to each other. We
      hypothesize that changes in UBQ11 ubiquitin repeat number occurred via the
      contraction and/or expansion of specific internal repeats or portions thereof by
      misalignment of alleles and recombination, most likely via unequal crossing-over
      events.

PMID- 9278166
TI  - Melon ascorbate oxidase: cloning of a multigene family, induction during fruit
      development and repression by wounding.
AB  - A small family of at least four genes encoding melon ascorbate oxidase (AO) has
      been identified and three members of it have been cloned. Preliminary DNA
      sequence determination suggested that melon AO genes code for enzymes homologous
      to ascorbate oxidases from other plants and similar to other multicopper
      oxidases. We describe detailed molecular studies addressing melon AO expression
      during organ specific differentiation, fruit development and ripening, and in
      response to wounding. In particular, AO transcript accumulation was induced in
      ovaries and the outer mesocarp of mature preclimacteric melon fruits, before the
      expression of genes encoding the necessary enzymatic activities for ethylene
      biosynthesis. On the other hand, AO was not expressed in late stages of fruit
      ripening and was repressed in wounded fruits. The role of ethylene in
      transcriptional regulation of AO is discussed.

PMID- 9278167
TI  - Cloning of a WD-repeat-containing gene from alfalfa (Medicago sativa): a role in
      hormone-mediated cell division?
AB  - Rhizobium meliloti can interact symbiotically with Medicago plants thereby
      inducing the formation of root nodules. Screening of a young nodule cDNA library
      led to the isolation of a cDNA from Medicago sativa, Msgbl, that comprises a new
      member of the RACK1 (Receptor of Activated C Kinase) subfamily of WD-repeat
      proteins. This subfamily shows homology to the beta-subunit of heterotrimeric G
      proteins. Besides RACK1, this subfamily contains several plant genes including
      the well characterized auxin-inducible ArcA of tobacco. The Msgbl gene is
      strongly expressed in young embryos and in leaves, and is induced upon cytokinin
      treatment of roots. Whereas northern analysis failed to reveal differences in
      expression between total RNA from roots and nodules, in situ hybridization
      demonstrated that the transcript was most abundant in dividing cells of nodule
      primordia and in the nodule meristem. Msgbl may be related to the signal
      transduction acting in response to hormone-mediated cell division.

PMID- 9278168
TI  - Molecular characterization of three differentially expressed members of the
      Camptotheca acuminata 3-hydroxy-3-methylglutaryl CoA reductase (HMGR) gene
      family.
AB  - Camptotheca acuminata is a Chinese tree that produces the anti-cancer
      monoterpenoid indole alkaloid camptothecin (CPT). 3-hydroxy-3-methylglutaryl
      coenzyme A reductase (HMGR) supplies mevalonate for the terpenoid moiety of CPT
      and its hydroxylated derivative 10-hydroxycamptothecin (10-OH-CPT). We previously
      described the isolation of a gene encoding HMGR from C. acuminata (hmg1) and
      analyzed its expression in transgenic tobacco [6]. Here, we report on the
      isolation of genomic (hmg2) and cDNA (hmg3) clones representing two additional
      HMGR gene family members and characterize the expression of all three genes in C.
      acuminata. Transcript levels for two family members were highest in the shoot
      apex, dry seeds (hmg1), and bark (hmg3) which are the tissues containing the
      highest levels of CPT and 10-OH-CPT respectively. Levels of hmg3 mRNA also
      correlated with the accumulation of 10-OH-CPT during germination. In C. acuminata
      leaf disks, hmg1 mRNA increased in response to wounding, and this induction was
      suppressed by methyl jasmonate (MeJA), in agreement with results previously
      obtained in transgenic tobacco [6]. In contrast, wounding and MeJA did not affect
      hmg2 or hmg3 transcript levels in C. acuminata. These results show that members
      of the C. acuminata HMGR gene family are differentially expressed in various
      tissues under different physiological conditions which may contribute to the
      regulation of monoterpenoid indole alkaloid synthesis in this species.

PMID- 9278170
TI  - Regulatory activity exerted by the SAUR-AC1 promoter region in transgenic plants.
AB  - SAUR-AC1 is a small-auxin-up-RNA (SAUR) gene of Arabidopsis. Here we demonstrate
      that the SAUR-AC1 promoter region induces accumulation of a reporter transcript
      upon treatment with auxin and is preferentially active in elongating hypocotyls
      and certain other organs and tissues of transgenic Arabidopsis and tobacco
      plants. This study extends the utility of the SAUR-AC1 gene by providing a
      foundation for comparative analyses of SAUR promoter activity in auxin-responsive
      mutants of Arabidopsis.

PMID- 9278169
TI  - Characterization of ppEG1, a member of a multigene family which encodes endo-beta
      1,4-glucanase in peach.
AB  - Three cDNA clones (pCel 10, pCel 20 and pCel 30), each encoding different endo
      beta-1,4-glucanases in peach, were obtained by RT-PCR and their expression
      investigated by northern analysis during leaf and fruit abscission and during
      fruit development. This analysis allowed the detection of only the pCel 10
      related mRNA. A 2.2 kb transcript accumulated in ethylene activated abscission
      zones of leaves and fruits, and ppEG1 (Prunus persica endoglucanase 1) the gene
      coding for pCel 10, was isolated and characterized. A cDNA (termed pCel 1),
      containing the entire open reading frame of ppEGC1, was obtained and its sequence
      used to define the structure of the gene and the exon/intron boundaries. ppEG1
      consists of 7 exons and encodes a 497 amino acid polypeptide including a putative
      signal peptide at the N-terminus. The similarity of this peach endo-beta-1,4
      glucanase (EGase, EC 3.2.1.4) is high (76.3%) with the ripening avocado and low
      (47.3%) with the bean abscission EGase. A 1639 bp region at the 5' of the
      transcription start site shows regulatory functions in transgenic tobacco plants,
      as judged by its ability to drive GUS expression in cell separation-related
      events.

PMID- 9278171
TI  - Identification of the tobacco and Arabidopsis homologues of the pollen-expressed
      LAT59 gene of tomato.
AB  - We describe the complete genomic sequences for the tobacco and Arabidopsis
      homologues of tomato LAT59, a previously described member of a family of pectate
      lyase-like genes. Translation of the tobacco gene, Nt59, predicts a protein with
      93.5% overall amino acid similarity to LAT59. Nt59 has two introns whose
      positions are exactly conserved with the two introns of LAT59. Both LAT59 and
      Nt59 are specifically expressed in pollen and their promoter and 5'-UTR sequences
      are highly similar. Furthermore, two promoter elements shown to be important for
      pollen expression of LAT59 are conserved in the Nt59 promoter. The Arabidopsis
      homologue, At59, was found by examination of four candidates. At59 has 72.6%
      amino acid similarity to LAT59 and the position of one of its two introns is
      conserved with one of the LAT59 introns. At59 is also pollen-expressed and
      although its promoter sequence is quite different from the Nt59 and LAT59
      promoters, the two promoter elements are somewhat conserved.

PMID- 9278172
TI  - Sequencing, expression pattern and RFLP mapping of a senescence-enhanced cDNA
      from Zea mays with high homology to oryzain gamma and aleurain.
AB  - Sequence analysis of a 1.4 kb clone from a cDNA library of senescing Zea mays
      leaves reveals an open reading frame for a 360 amino acid protein. Both the DNA
      and deduced amino acid sequences are highly homologous to the cysteine
      proteinases oryzain gamma and aleurain. Northern analysis demonstrates that the
      corresponding RNA level increases during natural leaf senescence, seedling
      germination and in chilling of tolerant maize lines, but decreases in a sensitive
      line. The mRNA level also decreases in regreening leaves, in dark-induced
      senescence and in nutrient or water stress. Southern and RFLP analysis provide
      evidence that the gene has two copies, on chromosomes 2 and 7.

PMID- 9278173
TI  - Transcription initiation sites for sorghum mitochondrial atp9 are positioned
      immediately 3' to trnfM.
AB  - Sorghum mitochondrial atp9 is polymorphic among male-sterile cytoplasms, but each
      cytoplasm is characterized by a major 650 nt transcript, regardless of fertility
      status. The gene is positioned 323 bp 3' to trnfM. Primer extension revealed
      multiple atp9 5' transcript termini, distributed from +1 to +28 3' to trnfM; the
      termini could be labeled with polynucleotide kinase, suggesting that they result
      from the maturation of trnfM. Guanylyltransferase experiments, however, showed
      that four of the termini were capable. The juxtaposition of a putative promoter
      3' to trnfM results in a unique atp9 transcript population consisting of primary
      and processed transcripts.

PMID- 9278174
TI  - Foldback transposable elements in plants.
AB  - A novel transposon family was discovered in plants. This family, designated SoFT
      (Solanaceae Foldback Transposon), exhibit striking structural similarity to the
      'foldback' class of animal transposons. SoFT elements consist of a middle segment
      surrounded by long terminal inverted repeats. Two of the identified SoFT elements
      have 'classical' foldback structure: their inverted repeats are divided into two
      domains. The outer domain consists of tandemly arranged subrepeats, whereas the
      inner domain is non-repetitive and AT-rich. The existence of foldback elements in
      plants as well as in animals suggests that long inverted repeat (foldback)
      transposons are ubiquitous among eukaryotes.

PMID- 9278175
TI  - Biodistribution of synthetic thymosin alpha1 in the serum, urine and major organs
      of mice.
AB  - Thymosin fraction 5 (TF5), a thymic preparation, has been shown to be an immune
      potentiating agent consisting of biologically active polypeptide components with
      hormone-like activities. Thymosin alpha1 (T alpha1) was the first biologically
      active polypeptide to be purified from TF5 and completely characterized. It is an
      acidic peptide with an isoelectric point of 4.2 and a molecular weight of 3108. T
      alpha1 is considered a biological response modifier which amplifies T-cell
      immunity. In the present study, we have studied some pharmacokinetic properties
      of T alpha1 by measuring its concentrations in serum, urine and ten major organs
      of female Swiss-Webster mice following administration of 500 microg T alpha1
      intraperitoneally. Using a modified enzymatic immunoassay, our data show a
      significant increase of T alpha1 in serum 2 min after injection and lasting for 2
      h (average: 1.55 +/- 0.27 microg/ml). In urine, at four different time points
      after injection (20 min, 40 min, 2 h, 6 h), increased concentrations of T alpha1
      were found between 24.2 and 25.4 microg/ml (average: 25 +/- 0.47 microg/ml). Of
      the 500 microg T alpha1 administered to mice, 8.97% was recovered at the end of
      the study, of which 2% corresponded to urine, 1.25% to serum (2 ml of serum per
      mouse), and 5.72% to organs. Since the urine/day volume and the serum volume of
      any Swiss Webster mouse is ca 2 ml, additional extrapolation of the above
      mentioned values could show percentages of recovery close to 40% for urine and
      2.5% for serum. In most of the organs, the wet weight concentrations of T alpha1
      increased significantly during the first 40 min after injection in comparison to
      their baseline wet weight concentrations. These organs consisted of the
      following: thymus (33.1 +/- 3.5 microg/g vs 18 microg/g baseline); lungs (7.7 +/-
      1.1 microg/g vs 1.9 microg/g baseline); spleen (15.6 +/- 0.7 microg/g vs 5.6
      microg/g); kidneys (6.2 +/- 1.1 microg/g vs 3.9 microg/g); ovaries (9.2 +/- 1.4
      microg/g vs 0 microg/g); and peritoneal fat (4 +/- 1 microg/g vs 0 microg/g). No
      significant increases were observed in the liver (1.7 +/- 0.1 microg/g vs 1.4
      microg/g) and heart (0.7 +/- 0.5 microg/g vs 0 microg/g). Increased
      concentrations of T alpha1 were not detected in the brain and skeletal muscle
      tissues. These pharmacokinetic studies of T alpha1 in mice indicate that rapid
      renal excretion of T alpha1 represents a major source of humoral loss following
      I.P. administration. Recent preliminary studies in humans confirm that the kidney
      rapidly releases high levels of T alpha1 in urine in a time frame consistent with
      that observed in mice.

PMID- 9278177
TI  - Upregulation of phagocytosis and candidicidal activity of macrophages exposed to
      the immunostimulant acemannan.
AB  - Previous studies by these investigators have shown that mannosylated bovine serum
      albumin (m-BSA) enhances the respiratory burst (RB), phagocytosis, and killing of
      Candida albicans by resident murine peritoneal macrophages (MO). Upregulation of
      the above MO functions was associated with binding of m-BSA to the MO-mannose
      receptor. The present study was done to determine if the immunostimulant,
      acemannan prepared from aloe vera, could stimulate MO in a similar manner.
      Resident peritoneal MO collected from C57BL/6 mice were exposed to acemannan for
      10 min. The RB was measured using chemiluminescence and demonstrated
      approximately a two-fold increase above the media controls. In studies involving
      phagocytosis, MO were exposed to acemannan, washed and exposed to Candida at a
      ratio of 1:5. The percent phagocytosis and Candida killing were determined using
      fluorescence microscopy. There was a marked increase in phagocytosis in the
      treated cultures (45%) compared to controls (25%). Macrophages exposed to
      acemannan for 10 min resulted in ca 38% killing of Candida albicans compared with
      0-5% killing in controls. If MO were incubated with acemannan for 60 min, 98% of
      the yeast were killed compared to 0-5% in the controls. The results of the
      present study indicate that short term exposure of MO to acemannan upregulates
      the RB, phagocytosis and candidicidal activity. Further studies are needed to
      clarify the potential use of this immunostimulant as an anti-fungal agent.

PMID- 9278178
TI  - Are immunoconjugates useful for therapy with autoimmune diseases?
AB  - Immunoconjugates or immunotoxins (ITs) are targeting molecules which consist of a
      monoclonal antibody together with a toxin--thereby they can selectively kill
      target cells in a highly efficient manner. The use of ITs as a drug targeting
      approach is one of the most attractive research fields for tumor therapy;
      however, the study of ITs for the treatment of autoimmune diseases has been given
      little attention until recently. It has been shown that ITs could help alleviate
      the symptoms of myasthenia gravis and rheumatoid arthritis in animal models. In
      the last 3 yr ITs have been used in clinical trials (phase I and phase II) for
      the treatment of various autoimmune diseases including rheumatoid arthritis,
      systemic lupus erythematosus, insulin-dependent diabetes mellitus and psoriasis.
      This article reviews the main progress on the application of ITs for the
      therapies of autoimmune diseases. The preliminary results suggest the future may
      hold some promise, but side effects, in addition to there being no convincing
      efficacy, remain unresolved.

PMID- 9278176
TI  - Preventive effect of a novel antifolate, MX-68, in murine systemic lupus
      erythematosus (SLE).
AB  - We evaluated the preventive effects of a novel nonpolyglutamatable antifolate, MX
      68, on two experimental murine models of systemic lupus erythematosus (SLE);
      NZBxNZW F1 (BWF1) mice and chronic graft-versus-host disease (GVHD) mice, in
      comparison with classical antifolate methotrexate (MTX). The oral administration
      of 2 mg/kg MX-68, three times a week from 12 to 40 or 60 weeks of age,
      significantly delayed the onset of proteinuria and prolonged the life-span of
      BWF1 mice. The elevation of serum blood urea nitrogen (BUN) and cholesterol
      levels resulting from the development of lupus nephritis was also inhibited.
      However, MX-68 did not suppress the increase of serum anti-DNA or anti-TNP
      antibodies or total IgG isotype (IgG1, IgG2 and IgG3) levels. In chronic GVHD
      mice, MX-68 given three times a week from the day of first cell injection, for 9
      weeks, dose-dependently delayed the appearance of proteinuria. The elevation of
      BUN and cholesterol levels was also inhibited. Furthermore, in the 4 mg/kg MX-68
      group, the production of IgG anti-DNA and anti-TNP antibodies was significantly
      inhibited, but this was not observed in the 2 mg/kg MX-68 and the 4 mg/kg MTX
      groups. These beneficial effects of MX-68 were much greater than those of MTX in
      both models. These results suggest that MX-68 might be a more useful drug for the
      treatment of SLE.

PMID- 9278179
TI  - Effects of morphine on purified human blood monocytes. Modifications of
      properties involved in antiviral defences.
AB  - It has been demonstrated that morphine stimulates the replication of human
      immunodeficiency virus in peripheral blood mononuclear cells as well as in
      Kupffer cells. Since the mechanism of action of this drug is still unknown, we
      have studied its effects on different properties of isolated human blood
      monocytes. In the presence of morphine, cultured monocytes showed an increase in
      the fluidity of their membranes as well as an inhibition in their capacity to
      differentiate into macrophages. Furthermore, the response of the cells to
      interferon-gamma was significantly decreased and the release of superoxide anions
      was altered. Finally the production of interferon-alpha and of prostaglandin E2
      induced by stimulation of the cells with endotoxin (LPS) was diminished. We
      conclude that morphine decreases the functions of monocytes that are essential
      for their antiviral defence and inhibits their response to activating stimuli,
      which may explain the increased multiplication of HIV in morphine treated
      monocytes.

PMID- 9278180
TI  - Photodynamic effect on the specific antitumor immune activity.
AB  - Photofrin is a potent sensitizer which localizes, among other sites in membranes
      of malignant cells. To evaluate the effect of photodymanic therapy (PDT) on
      specific antitumoral immunological response, we used a chromium release assay to
      compare the specific cytolytic activity (CLA) of primed mouse spleen T
      lymphocytes sensitized against syngeneic mastocytoma P511 cells. P511 cells or
      lymphocytes or both were treated or not with Photofrin and/or light (514 nm).
      Photofrin alone (1 microg/ml, 2 h) reduced CLA by 59% when P511 cells were
      treated although this decrease was not drug dose dependent. Photofrin (1
      microg/ml, 2 h) followed by light (25 J/cm2) reduced CLA by 35% in a drug dose
      dependent manner. Longer incubation times led to reduced CLA inhibition (10% for
      3 h incubation) after Photofrin followed by light. The light dose (25, 37, 50
      J/cm2) did not influence CLA for a given Photofrin concentration. Photofrin alone
      (0.5 microg/ml, followed by light (25 J/cm2 for 2 h) reduced CLA respectively by
      8 and 45% only when lymphocytes were treated. When lymphocytes and P511 cells
      were treated with Photofrin alone or followed by light (25 J/cm2), CLA was also
      reduced (by 19 and 41% respectively). This type of damage can be evaluated in
      terms of antigen expression on the target cells, on the lymphocyte T receptor, on
      H-2 (histocompatibility major complex), or on lymphocyte activity after PDT.

PMID- 9278181
TI  - In vitro effect of gold sodium thiomalate and methotrexate on tumor necrosis
      factor production in normal healthy individuals and patients with rheumatoid
      arthritis.
AB  - We studied the in vitro action of gold sodium thiomalate (GSTM) and Methotrexate
      (MTX) on spontaneous and lipopolysaccharide (LPS) stimulated TNF alpha production
      by peripheral blood mononuclear cells (PBMC) of patients with rheumatoid
      arthritis (RA) and normal healthy individuals. GSTM and MTX (10 microg) each were
      added to the cultures of PBMC either in medium alone (spontaneous) or in the
      presence of 10 microg of LPS. GSTM and MTX augmented spontaneous TNF alpha
      production in normal individuals and patients with RA but did not influence LPS
      stimulated TNF alpha production. However, TNF alpha production by the PBMC of
      normal individuals was inhibited if the PBMC were stimulated with LPS, for 6 or
      12 h, washed to remove LPS and subsequently incubated with GSTM. These data
      indicate that GSTM can inhibit TNF alpha production when the PBMC are
      preactivated by LPS.

PMID- 9278182
TI  - The effects of anesthesia with thiopental on T lymphocyte responses to antigen
      and mitogens in vivo and in vitro.
AB  - In this study we show that antigen-specific lymphocyte proliferation and
      interleukin (IL)-2 production by peripheral blood lymphocytes from patients under
      thiopental anesthesia are significantly depressed. In contrast, mitogen-induced
      lymphocyte proliferation and IL-2 secretion are not depressed. We have also shown
      that tetanus toxoid (TT) specific CD4+ T cell clones, with a known cytokine
      production profile, were sensitive to the inhibitory effects of thiopental and
      exhibited decreased proliferation to TT as well as decreased secretion of IL-2.
      We observed no difference regarding IL-4 production by these clones. The data
      suggest that the immunosuppressive effect of thiopental is confined to antigen
      specific responses. In addition, we have shown that whereas IL-2 and interferon
      gamma production is dramatically impaired by the drug, IL-4 production is not
      significantly altered. This last finding has important implications regarding the
      type of immune response that is most affected by this anesthetic agent. In spite
      of the transient decrease in antigen-driven IL-2 synthesis, no clinical evidence
      of infection was noted in any healthy patient.

PMID- 9278183
TI  - Postmortem studies in schizophrenic brain.

PMID- 9278184
TI  - Neuropathological studies of brain tissue in schizophrenia.
AB  - Postmortem neuropathological investigations in the last half decade provide
      increasing evidence compatible with a neurodevelopmental defect in schizophrenia.
      Basic and clinical data support hypotheses suggesting that disturbances in
      neurodevelopment in schizophrenia may involve the cortical subplate and a
      theorized second trimester "window of vulnerability". The focus of this paper is
      on (1) selected methodological issues involved in the collection, analyses and
      preservation of human postmortem brain tissue; (2) a review of evidence showing
      morphological defects particularly in prefrontal cortical regions of the
      schizophrenic brain; and (3) potential future research directions.

PMID- 9278186
TI  - Limbic circuits and monoamine receptors: dissecting the effects of antipsychotics
      from disease processes.
AB  - There is considerable evidence for the involvement of brain dopaminergic and
      serotonergic systems in schizophrenia pathology. However, post-mortem studies
      have been limited by difficulties in separating the effects of chronic exposure
      to antipsychotics from that of the disease process. Our recent studies directly
      explored this by comparing groups that were free from antipsychotic treatment for
      up to a year prior to death and that were maintained on antipsychotics. We have
      used this approach to identify that there are prominent effects of both disease
      and of antipsychotic treatment. There appears to be a high association for
      schizophrenics between elevations of D3 receptors in target regions of the
      mesolimbic dopamine (DA) system and elevated numbers of 5-HT(1A) receptors in
      prefrontal cortex (PFc). Antipsychotic treatment was correlated with a reduction
      of D3 receptors in the ventral striatum and its output structures. It also led to
      a reduction in the number of 5-HT2 receptors in some regions of the PFc without
      modifying the concentration of 5-HT(1A) receptors. The limbic loop
      interconnecting the PFc and ventral striatum may be the site of antipsychotic
      regulation of certain symptoms in schizophrenia, particularly anhedonia and
      depression. The positive symptoms of schizophrenia are more likely to be
      associated with disturbances in the temporal lobe. However, dopaminergic systems
      in the temporal lobe have historically been thought to be underdeveloped compared
      to that in the basal ganglia and unlikely to be the target of antipsychotics. Our
      studies of the expression of the DA D2 receptor in the temporal lobe has shown a
      complex organization in the perirhinal and temporal cortices that is disrupted in
      schizophrenia. The disturbances, which might be of neurodevelopmental origin and
      are unrelated to antipsychotic treatment, include altered laminar distribution of
      the D2 receptor and modified modular organization of D2 receptors in the superior
      temporal gyrus. We hypothesize that modified expression of D2 receptors in these
      regions play a key role in the genesis of hallucinations. Treatment with
      antipsychotics leading to D2 receptor blockade in temporal cortex may reduce the
      presence of positive symptoms.

PMID- 9278185
TI  - Cortical dopamine in schizophrenia: strategies for postmortem studies.
AB  - Many of the symptoms of schizophrenia appear to involve dysfunction of the
      cognitive processes mediated by the neural circuitry of the cerebral cortex. The
      application of modern neuroscience techniques to the study of postmortem human
      brain specimens provides a powerful approach for exploring the manner in which
      cortical circuitry may be disrupted in schizophrenia. In this paper, we describe
      a strategy for the conduct of postmortem investigations of schizophrenia that
      involves (1) the use of a nonhuman primate model to guide the design and
      interpretation of studies in humans; (2) the detailed characterization of the
      normal organization of neural systems in the human cerebral cortex, and the range
      of inter-individual variations in that organization; and (3) the testing of
      specific hypotheses about the disruption of that organization in schizophrenia.
      The application of this strategy, and its value in overcoming some of the
      potential pitfalls of postmortem studies, is demonstrated in a series of
      investigations designed to test the hypothesis that dopamine neurotransmission is
      impaired in the entorhinal cortex in schizophrenia.

PMID- 9278187
TI  - Review the role of dopamine D4 receptors in schizophrenia and antipsychotic
      action.
AB  - For the past 20 years the most enduring explanation for schizophrenia has been
      the dopamine hypothesis, which proposes that the dopaminergic system is
      overactive in this widespread disease. Classically, the D2 receptor formed the
      core of the dopamine hypothesis since there was considerable evidence for
      elevations of D2 receptor levels in the brains of schizophrenic patients, and
      because these receptors served as the primary target in mediating antipsychotic
      effects of most neuroleptics. However, the dopamine D4 receptor has recently
      received particular attention in this context. This is because the atypical
      antipsychotic, clozapine, which is effective in treating refractory
      schizophrenics without the side-effect profile of typical neuroleptics, displays
      a 10-fold higher affinity for D4 compared to D2 or D3 receptors. Furthermore, the
      concentration in plasma water of clinical doses ofclozapine correlates well with
      its in vitro binding affinity for D4, but not D2 or D3 receptors, suggesting that
      D4 is a potential target in mediating clozapine's antipsychotic effects. As well,
      marked elevations in the level of a D4-like site (not identical to the D4
      receptor) has been seen in the striatum of postmortem schizophrenic brains, but
      not in control brains. Finally, the most interesting feature of the D4 receptor
      is perhaps the array of polymorphisms associated with it, creating structural
      diversity in this receptor that supercedes all other known catecholamine
      receptors. The existence of these D4 polymorphisms raises the possibility that
      structural variations of this receptor may be associated with an increased
      susceptibility to schizophrenia, or observed variations in individual response to
      clozapine treatment. However, several studies aimed at investigating these
      hypotheses could not establish a direct role of D4 in schizophrenia. Furthermore,
      no association was evident between the polymorphic forms of D4 and susceptibility
      to schizophrenia, or variable clozapine response. Nevertheless, investigations
      surrounding this receptor has been far from futile. The observations which
      support the idea that D4 might serve as a target for clozapine have significantly
      modified and extended our understanding of mechanisms underlying atypical
      antipsychotic treatment of schizophrenia, as well as the dopamine hypothesis for
      schizophrenia. Further characterization of this receptor may prove to be crucial
      in designing highly effective antipsychotic drugs with minimal contraindications.

PMID- 9278188
TI  - Abnormal cholecystokinin mRNA levels in entorhinal cortex of schizophrenics.
AB  - Limbic cortical regions, including anterior cingulate cortex (ACC), prefrontal
      cortex (PFC) and entorhinal cortex (ERC), have been implicated in the
      neuropathology of schizophrenia. Glutamate projection neurons connect these
      limbic cortical regions to each other, as well as to the terminal fields of the
      striatal/accumbens dopamine neurons. Subsets of these glutamate projection
      neurons, and of the GABA interneurons in cortex, contain the neuropeptide
      cholecystokinin (CCK). In an effort to study the limbic cortical glutamate
      projection neurons and GABA interneurons in schizophrenia, we have measured CCK
      mRNA with in situ hybridization histochemistry in postmortem samples of
      dorsolateral (DL)PFC, ACC and ERC of seven schizophrenics, nine non-psychotic
      suicides and seven normal controls. CCK mRNA is decreased in ERC (especially
      layers iii vi) and subiculum in schizophrenics relative to controls. Cellular
      analysis indicates that there is a decrease in density of CCK mRNA in labelled
      neurons. In so far as ERC CCK mRNA is not reduced in rats treated chronically
      with haloperidol, this decrease in schizophrenics does not appear to be related
      to neuroleptic treatment. In contrast, in DLPFC, where schizophrenics do not
      differ from normals, the suicide victims have elevated CCK mRNA (especially in
      layers v and vi), and increased cellular density of CCK mRNA, relative to both
      normals and schizophrenics. These results lend further support for the
      involvement of ERC and hippocampus in schizophrenia, suggesting that neurons that
      utilize CCK may be particularly important. Similarly, an increase in CCK mRNA
      levels in the PFC of suicides adds to a growing body of evidence implicating this
      structure in this pathological state. In so far as CCK is co-localized with GABA
      or glutamate in cortical neurons, both of these neuronal populations need to be
      studied further in schizophrenia and suicide.

PMID- 9278189
TI  - The role of stress and dopamine-GABA interactions in the vulnerability for
      schizophrenia.
AB  - Current hypotheses concerning the etiology of schizophrenia often invoke both an
      abnormal gene(s) and an environmental disturbance as necessary components to the
      vulnerability for this disorder. According to one model of schizophrenia
      presented here, the putative environmental factor may consist of stress and
      require both pre- and post-natal exposure for a "mis-wiring" of dopaminergic
      inputs to GABAergic neurons of the cortex to occur. Since the cortical dopamine
      system continues to mature until the start of the early adult period, the normal
      ingrowth of dopamine fibers during late adolescence and their formation of
      aberrant connections with abnormal intrinsic corticolimbic circuits could
      "trigger" the onset of symptoms in those who carry the constitutional
      vulnerability for schizophrenia.

PMID- 9278190
TI  - A two-process theory of schizophrenia: evidence from studies in post-mortem
      brain.
AB  - Glutamate and GABA are the principle neurotransmitters of the cerebral cortex and
      are known to modulate dopaminergic function. Evidence of structural abnormalities
      in the cortex raises the possibility that schizophrenia involves disturbances of
      cortical amino-acid neurotransmission. The psychotomimetic effects of
      phencyclidine, a glutamate antagonist, have been taken to suggest that
      schizophrenia involves reduced brain glutamate function. Direct evidence for
      diminished glutamate function in schizophrenia is lacking. However, in polar
      temporal cortex and hippocampus we reported evidence of an asymmetric loss of
      glutamate terminals, and of reduced GABA function, which may be secondary to the
      loss of glutamatergic input. Glutamate cell body markers are spared in temporal
      lobe; the neurones which degenerate may originate in frontal cortex. A number of
      studies have reported increases in markers of glutamatergic cell bodies and
      terminals in orbital frontal cortex in schizophrenia. These findings are
      consistent with the presence of an abnormally abundant glutamatergic innervation,
      which may be the result of an arrest in the normal process of cellular and
      synaptic elimination which occurs during development. There is evidence that
      frontal abnormalities in schizophrenia are genetically determined. We suggest
      that glutamatergic abnormalities in anterior temporal cortex in schizophrenia are
      the result of the degeneration of fronto-temporal projections. Orbital frontal
      projections to polar temporal cortex may be prone to degeneration because they
      arise from an unstable frontal cortical cytoarchitecture which has not completed
      the normal process of post-natal remodelling. The structural abnormality of the
      orbital frontal region may confer vulnerability to some intrinsic or extrinsic
      mechanism, which brings about a progressive degeneration of projections to polar
      temporal lobe.

PMID- 9278191
TI  - Education in clinical pharmacology and therapeutics in a changing world.

PMID- 9278192
TI  - Pharmacovigilance in the 1990s.

PMID- 9278193
TI  - Beta-adrenoceptor blockers in chronic heart failure--a review.
AB  - There are now considerable clinical trial data to support the use of beta
      adrenoceptor blockers in patients with chronic heart failure due to systolic left
      ventricular dysfunction. Increases in ejection fraction, improved well-being as
      judged by both patient and physician and reduced progression of ventricular
      dysfunction have been demonstrated. From meta-analyses of available trial data, a
      mortality reduction of approximately 30% is obtained when these drugs are added
      to standard heart failure therapies. Furthermore, reductions in cardiovascular
      morbidity associated with decreased hospitalization rates suggest
      pharmacoeconomic benefits with these agents. This review addresses the following
      issues regarding beta-adrenoceptor blockers in chronic heart failure: the known
      adverse effects of chronic sympathetic activation in heart failure, the
      theoretical benefits of blockade of this neurohormonal system, the current
      clinical database of beta-adrenoceptor blockers in heart failure and practical
      issues regarding the administration of these agents to these patients.

PMID- 9278194
TI  - Enantioselective pharmacokinetics of mefloquine during long-term intake of the
      prophylactic dose.
AB  - AIMS: To investigate the kinetics of the (+)RS- and (-)SR-enantiomers and the
      carboxylic acid metabolite (MMQ) of the antimalarial drug mefloquine (MQ) in
      healthy volunteers. METHODS: Ten subjects of which three were poor metabolizers
      of debrisoquine received racemic MQ 250 mg once weekly for 16 weeks. The kinetics
      were followed in plasma and urine and evaluated by individual kinetic modelling
      as well as by a nonparametric population kinetic method. RESULTS: A two
      compartment model adequately described the disposition of (+)RS-MQ. CL/F was 6.5
      +/- 1.8 l h(-1), V(ss)/F 815 +/- 165 l, and k 0.0081 +/- 0.0023 h(-1). The
      kinetics of (-)SR-MQ were time- and/or concentration dependent with a lower oral
      clearance (0.92 +/- 0.25 vs 2.14 +/- 0.63 l h(-1), 95% CI for the difference 0.86
      1.60 l h(-1)) and a longer half-life (345 vs 185 h, 95% CI for the difference 47
      291 h) after the last dose compared with the first dose. Clearance of (+)RS-MQ
      and (-)SR-MQ was significantly correlated within subjects (r = 0.69, P < 0.05).
      Urinary recovery of unchanged substance was 8.7% for (+)RS-MQ and 12.3% for (-)SR
      MQ. The elimination of MMQ was disposition rate-limited and not determined by its
      rate of formation. Poor metabolizers of debrisoquine did not differ from
      extensive metabolizers in the kinetics of any compound. CONCLUSIONS: The MQ
      enantiomers differ extensively in their disposition both with regard to parameter
      values and the kinetic stability over time during repeated dosing with racemic
      MQ. Kinetic modelling of racemic MQ is therefore inadequate.

PMID- 9278195
TI  - Cyclosporin pharmacokinetics following administration of capsules and Neoral in
      paediatric patients with lupus nephritis.
AB  - AIMS: Neoral is a new microemulsion form of cyclosporin. Pharmacokinetic reports
      in children are scarce. Therefore, we performed a pharmacokinetic study between
      Cyclosporin A (CsA) capsules and Neoral in paediatric patients with lupus
      nephritis. METHODS: A single 5 mg kg(-1) dose orally of either CsA capsules or
      Neoral was given to 10 paediatric patients (serum creatinine < 1.5 mg dl(-1)).
      CsA whole blood levels were measured for 24 h post-dose by h.p.l.c. RESULTS:
      Neoral had a higher C(max) and AUC(C(max): 943 +/- 176 ng ml(-1); AUC: 4612 +/-
      785 ng ml(-1) h) than those of the CsA capsules (C(max): 697 +/- 187 ng ml(-1);
      AUC: 3483 +/- 873 ng ml(-1) h; P < 0.05). There was no difference in t(max) and
      t(1/2,z) between the two groups. CONCLUSIONS: CsA Neoral had improved absorption
      and bioavailability, which is similar to what is reported in adults. However,
      interpatient variability still existed. Careful drug monitoring and dose
      adjustment should be performed during treatment to avoid nephrotoxicity,
      especially in lupus nephritis.

PMID- 9278196
TI  - Single and multiple dose pharmacokinetics of felbamate in the elderly.
AB  - AIMS: The objective of this study was to compare the pharmacokinetics, safety and
      tolerability of the antiepileptic drug felbamate in young and elderly healthy
      vounteers. METHODS: The single and multiple dose pharmacokinetics of felbamate
      were examined in an open-label two-dose level parallel group study in 24 elderly
      (66 to 78-year-old) and 11 young (18 to 45-year-old) healthy volunteer subjects.
      Pharmacokinetics were determined from blood samples obtained over 120 h after
      administration of single 600 mg or 1200 mg doses, and after multiple doses of 600
      mg or 1200 mg administered every 12 h. Safety and tolerability were assessed
      through laboratory tests, ECGs, vital signs and reported adverse events. RESULTS:
      Single dose felbamate pharmacokinetic parameters differed between young and
      elderly subjects; compared with young subjects, elderly subjects had lower mean
      clearance (31.2 vs 25.1 ml min(-1); 90% CI -11.4 to -0.9; P = 0.02) and a trend
      towards a greater half-life (18.6 vs 21.0 h; 90% CI -0.6 to 5.4; P = 0.11). Mean
      AUC and C(max) values were also higher in elderly subjects. No gender differences
      were noted for weight-adjusted pharmacokinetic variables. Felbamate was less well
      tolerated in elderly subjects compared with young subjects, as shown by higher
      rates of adverse event reporting and dropouts at the higher dose level. This may
      be due to age-related pharmacokinetic differences, to the rapid dose titration
      schedule used in this study, and/or to altered sensitivity to felbamate's
      pharmacodynamic effects. CONCLUSIONS: These findings imply that elderly subjects
      require lower initial dosing and slower dose titration of felbamate than non
      elderly subjects.

PMID- 9278197
TI  - Pharmacokinetics of digoxin-specific Fab: effects of decreased renal function and
      age.
AB  - AIMS: To study the influence of age and renal function on digoxin-specific Fab
      (DS-Fab) pharmacokinetics. METHODS: Sixteen patients (35-91 years) with
      creatinine clearance ranging from 10.6 to 122.1 ml min(-1) who had been admitted
      to hospital with severe digoxin or digitoxin self-poisoning were treated with DS
      Fab (80 to 800 mg). Plasma DS-Fab concentrations were determined by
      radioimmunoassay. RESULTS: The mean (s.d.) distribution and elimination half
      lives, apparent volume of distribution and total body clearance were 1.1 +/- 0.4
      h, 20.2 +/- 7.3 h, 13.1 +/- 5.8 l, and 17.6 +/- 10.8 ml min(-1), respectively.
      Interindividual variability of DS-Fab total body clearance was linked linearly
      with the decrease in creatinine clearance or with the increase in age and DS-Fab
      distribution volume was not dependent on creatinine clearance or age.
      CONCLUSIONS: The data suggest that DS-Fab should be given to elderly and renal
      impaired patients at doses similar to those given to younger or normal renal
      function patients.

PMID- 9278198
TI  - The pharmacokinetics and pharmacodynamics of rocuronium in patients with hepatic
      cirrhosis.
AB  - AIMS: To determine the effects of hepatic cirrhosis on the pharmacodynamics and
      pharmacokinetics of rocuronium bromide. METHODS: We studied 21 healthy patients
      and 17 patients with mild or moderate cirrhosis (Child-Pugh Class A and B).
      Patients were premedicated with diazepam orally; anaesthesia was induced with
      fentanyl and thiopentone, and maintained with isoflurane 0.6% (end-tidal) and
      nitrous oxide 66% in oxygen. The compound action potential of the adductor
      pollicis muscle in response to supramaximal stimulation of the ulnar nerve was
      recorded using the train-of-four (TOF) twitch technique. A bolus dose of
      rocuronium 0.6 mg kg(-1) was then given. Venous blood samples were taken for up
      to 8 h, and plasma rocuronium concentrations determined by h.p.l.c. RESULTS: The
      time to onset of neuromuscular block and maximal block achieved did not differ
      between the two groups. The mean (s.d.) recovery times were prolonged in the
      cirrhotic compared with the healthy group: 25% recovery T1:T0, 53.7 (18.1) vs
      42.3 (14.2) min; 50% recovery T1:T0, 73.9 (33.9) vs 52.6 (19.8) min; 75% recovery
      T1:T0, 84.2 (24.5) vs 66.8 (27.2) min (all P<0.05); recovery of T4:T1 to 70%,
      114.9 (31.7) vs 76.1 (28.8) min (P<0.01). A pharmacokinetic and pharmacodynamic
      model was fitted to the data for each patient. Three compartments were used to
      model the pharmacokinetic data; an effect compartment was added to model the
      pharmacodynamic data. Plasma clearance was significantly reduced in the cirrhotic
      group (2.66 (0.60) vs 3.70 (1.03) ml kg(-1) min (-1); P<0.005). The central (V1)
      and steady state volumes of distribution (V(ss)) did not differ significantly
      between the groups. The slow redistribution (t1/2,lambda1) and elimination
      (t1/2,z) half-lives were both significantly prolonged in cirrhosis (28.3 (12.1)
      vs 16.8 (4.6) min, P < 0.005; and 143 (80) vs 92 (40) min, P < 0.05
      respectively). The exit rate constant for the effect compartment k(eo) was
      significantly increased in the cirrhotic group (0.25 (0.18) vs 0.16 (0.06) min(
      1); P < 0.05), but cirrhosis had no significant effect on the parameters of the
      concentration-effect relationship Cp(ss)(50) and gamma. CONCLUSIONS: Hepatic
      elimination is an important pathway in the clearance of rocuronium, and delayed
      disposition causes the effect to be prolonged.

PMID- 9278199
TI  - Do trandolapril and indomethacin influence renal function and renal functional
      reserve in hypertensive patients?
AB  - AIMS: To assess the effect of trandolapril (2 mg once daily) and indomethacin (25
      mg three times daily), alone and in combination, on renal function and renal
      functional reserve in hypertensive patients (DBP 95-115 mmHg) requiring regular
      non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: Randomized, double
      blind, placebo-controlled, four way crossover design. After 3 weeks treatment
      renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured using
      the p-aminohippurate (PAH) and inulin methods. Renal functional reserve was
      estimated by measuring RPF and GFR at the end of an intravenous infusion of
      dopamine 2 microg kg(-1) and 10% amino acid solution. RESULTS: There was no
      significant difference in RPF between treatments: -22.79 ml min(-1) (95% CI 
      54.82, 9.24) for placebo and trandolapril, -10.37 ml min(-1) (95% CI -30.7, 9.96)
      for placebo and indomethacin, -14.78 ml min(-1) (95% CI -50.33, 20.77) for
      placebo and trandolapril with indomethacin. There was no significant difference
      in functional reserve RPF between treatments: -34.96 ml min(-1) (95% CI -119.8,
      49.88) for placebo and trandolapril, 29.78 ml min(-1), -15.18, 74.74) for placebo
      and indomethacin, and -25.84 ml min(-1) (95% CI -87.62, 35.94) for placebo and
      trandolapril with indomethacin. There was no significant difference in GFR
      between treatments: -1.01 ml min(-1) (95% CI -7.45, 5.42) for placebo and
      trandolapril, -7.88 ml min(-1) (95% CI -15.08, -0.68) for placebo and
      indomethacin, and -0.36 ml min(-1) (95% CI -7.58, 6.86) for placebo and
      trandolapril with indomethacin. There was no significant difference in functional
      reserve GFR between treatments: 5.13 ml min(-1) (95% CI -4.97, 15.23) for placebo
      and trandolapril, 6.31 ml min(-1) (95% CI -1.88, 14.5) for placebo and
      indomethacin, 7.21 ml min(-1) (95% CI 1.26, 13.16) for placebo and trandolapril
      with indomethacin. CONCLUSION: In hypertensives chronic treatment with NSAIDs or
      ACEI alone or in combination did not change RPF or GFR and did not change renal
      functional reserve capacity of RPF or GFR.

PMID- 9278200
TI  - A comparison of the effects of aspirin on bleeding time measured using the
      Simplate method and closure time measured using the PFA-100, in healthy
      volunteers.
AB  - AIMS: The aim of this study was to compare the effects of aspirin on platelet
      function as measured by the 'classical' template bleeding time with a new ex vivo
      method measuring closure times using the PFA-100 machine. Platelet aggregation in
      response to arachidonic acid was also measured ex vivo. METHODS: The trial was a
      randomized, double-blind, placebo-controlled crossover design, with each
      volunteer taking 750 mg aspirin (BP) or placebo, three times a day for 5 days,
      with an 18 day wash-out period between treatments. Bleeding times and closure
      times were measured before the first dose on the first day and 0.5 h after the
      last dose on the fifth day of each treatment period. They were also measured 2
      weeks after the last day of the trial. RESULTS: Baseline bleeding times (pre
      placebo) were 415 s using the Simplate, whilst baseline closure times were 115 s
      using the PFA-100. Aspirin treatment caused an increase of both the template
      bleeding time (61%) and the closure time of the PFA-100 (79%) when compared with
      the effects of placebo. The platelet aggregatory response to arachidonic acid was
      completely inhibited following aspirin treatment and was unaffected following
      placebo. Two weeks after the end of the trial, all values had returned to pre
      treatment levels. The template bleeding time was unaltered in 1 of the 12
      volunteers during aspirin treatment and was significantly prolonged in 3 of the
      12 volunteers during placebo treatment. The PFA-100 closure time was unaltered in
      1 of the 12 volunteers during aspirin treatment and was prolonged in 1 subject
      during placebo treatment. CONCLUSIONS: The change in closure time using the PFA
      100 is as sensitive and reproducible to the effects of aspirin on platelet
      function as is the template bleeding time test. However, the PFA-100 produced
      less variable effects with fewer false positive results.

PMID- 9278201
TI  - Chloroquine-induced pruritus in malaria fever: contribution of malaria
      parasitaemia and the effects of prednisolone, niacin, and their combination,
      compared with antihistamine.
AB  - AIMS: Chloroquine treatment of malaria fever, results in a generalized pruritus
      of unknown mechanism in up to 60% of adult Africans, by contrast pruritus is
      unusual in Caucasians following chloroquine use. METHODS: We conducted a double
      blind, randomized, parallel group study to examine and compare the antipruritic
      effects of promethazine, niacin, prednisolone and their combination on pruritus
      induced by chloroquine, in 28 historical itching patients with parasitologically
      proven malaria fever. We also evaluated the role of the antecedent malaria
      parasite density in the severity of chloroquine pruritus intensity. RESULTS: The
      concurrent administration of chloroquine (2.1 g base total dose) with
      prednisolone caused a statistically significant reduction in the pruritus AUC (0,
      72 h) (P < 0.001 ANOVA) compared with the antihistamine promethazine alone. The
      areas under the pruritus intensity-time curve were promethazine 105 +/- 28 (units
      h), niacin 76 +/- 22, prednisolone 28 +/- 24, and prednisolone and niacin 34 +/-
      17 (P < 0.001 ANOVA). The 95% confidence interval for the difference in the
      pruritus AUC between prednisolone and promethazine was 8.4 to 145.6 units h.
      There was a statistically significant and positive correlation between the
      pruritus intensity (AUC 0, 72 h) and the malaria parasite load in the itching
      subjects, not receiving prednisolone (n = 9) (r = 0.73, P = 0.026 ANOVA).
      CONCLUSION: A single oral dose of prednisolone (10 mg) may be preferable to the
      antihistamine promethazine (25 mg) as an antipruritic agent for concurrent
      prescription with chloroquine in individuals predisposed to severe itching.
      Malaria parasite clearance and clinical amelioration were unaffected by any of
      the treatments.

PMID- 9278202
TI  - An investigation of hospital generated pharmaceutical care when patients are
      discharged home from hospital.
AB  - AIMS: To investigate how seamless pharmaceutical care could be delivered.
      METHODS: Elderly patients discharged from hospital, to their own home, were
      randomized into control and study groups. Control and study group patients
      received the normal discharge information. The study group were also counselled
      about their medicines and informed about their pharmaceutical care plan. Copies
      of the plan were given to the study patients. All patients received a domiciliary
      visit between 7 and 10 days after discharge. Their current medication was
      compared with that on discharge and contact was made with the General
      Practitioner as appropriate. RESULTS: Twenty-eight study and 25 control patients
      with a mean (s.d.) age of 77.5 (7.3) and 77.6 (6.1) years completed the study. A
      pharmaceutical domiciliary visit was necessary for 21 (75%) and 24 (96%) of the
      study and control patients respectively. Compliance was better (P < 0.01) in the
      study group. Unintentional changes to the medication of 31 (14 study and 17
      control) patients were found during the visit and after contact with the
      prescriber all but one prescription was restored to that on discharge.
      CONCLUSIONS: At present it is difficult to ensure seamless pharmaceutical care. A
      pharmaceutical domiciliary visit may be useful to ensure seamless therapeutic
      care and thus avoid unnecessary healthcare events and costs after a patient is
      discharged home.

PMID- 9278203
TI  - Developing a core curriculum in clinical pharmacology and therapeutics: a Delphi
      study.

PMID- 9278204
TI  - Core content of a course in clinical pharmacology.

PMID- 9278205
TI  - Omeprazole, other antiulcer drugs and newly diagnosed gout.
AB  - AIMS: Case-reports describing patients who developed a first episode of acute
      gout while being treated with the proton pump inhibitor omeprazole led us to
      compare incidence rates of newly diagnosed gout cases among omeprazole,
      ranitidine and cimetidine users. METHODS: We conducted a cohort study with a
      nested case-control analysis using the UK-based General Practitioner Research
      Database (GPRD). The study encompassed a cohort of more than 53,000 subjects who
      received some 185,000 prescriptions for the three study drugs. RESULTS: Neither
      current omeprazole vs recent use (age- and sex-adjusted relative risk 1.1, 95% CI
      0.5-2.1), nor current omeprazole use in comparison with current use of the two
      histamine H2-receptor blockers was associated with an increased risk of
      developing newly diagnosed gout. Higher age (RR 2.4, 95% CI 1.5-3.9), male gender
      (RR 5.4, 95% CI 2.8-10.3), high body mass index (OR 3.3, 95% CI 1.0-10.9) and
      hypertension (OR 4.5, 95% CI 1.6-12.9) were all important risk factors for gout.
      CONCLUSIONS: While other known risk factors were significantly associated with
      gout, current omeprazole use was not materially associated with an increased gout
      incidence.

PMID- 9278206
TI  - Is metronidazole teratogenic? A meta-analysis.
AB  - AIM: In order to assess whether the use of metronidazole during pregnancy is
      associated with a higher risk of congenital malformations, a meta-analysis was
      conducted. METHODS: All epidemiological studies (cohort and case-control) which
      estimate risk of congenital malformations after exposure to metronidazole during
      early pregnancy were included in the meta-analysis. To obtain a summary odds
      ratio, the Mantel-Haenszel method was used. A test to verify absence of
      heterogeneity was also performed. RESULTS: One unpublished case-control and four
      published cohort studies fulfilled the inclusion criteria and were not
      statistically heterogeneous. A summary odds ratio was calculated for
      metronidazole exposure during the first trimester: OR = 1.08, 95% CI: 0.90-1.29,
      heterogeneity test chi2 = 4.72, P = 0.32. CONCLUSIONS: This meta-analysis did not
      find any relationship between metronidazole exposure during the first trimester
      of pregnancy and birth defects.

PMID- 9278207
TI  - Pharmacokinetics of the S(+) and R(-) enantiomers of vigabatrin during chronic
      dosing in a patient with renal failure.
AB  - AIMS: To study the pharmacokinetics of vigabatrin in a patient affected with
      tuberous sclerosis who developed major agitation and aggression, while receiving
      vigabatrin orally (1.5 g every 12 h) and in whom impaired renal function was
      diagnosed. METHODS: The patient received vigabatrin (0.5 g day(-1)). A
      pharmacokinetic study of the S(+) and R(-) enantiomers of vigabatrin was
      performed before and during dialysis. Plasma concentrations were measured at 0,
      1, 2, 3, 4, 6, 12, 18 and 24 h by a specific GCMS assay. RESULTS: Before
      dialysis, the maximum and minimun plasma concentrations of vigabatrin at steady
      state were lower for the S(+) than for the R(-) enantiomer, while the apparent
      oral clearance was higher for the S(+) than for the R(-) enantiomer (2.97 vs 0.48
      l h(-1)). In addition, the haemodialysis clearance was similar for the two
      enantiomers (4.96 vs 5.15 l h(-1)). CONCLUSIONS: Vigabatrin is an irreversible
      inhibitor of GABA-transaminase, effective in the treatment of drug-resistant
      epilepsy and reported to be eliminated unchanged by renal excretion. Although
      vigabatrin is known to have stereoselective kinetics, the difference in plasma
      dry concentrations and pharmacokinetics of the S(+) and R(-) enantiomers that we
      observed during long term administration at high doses in a patient with impaired
      renal function, has not been reported before. The question remains of the
      potential toxicity of the high levels of the R(-) enantiomer.

PMID- 9278208
TI  - Carbamazepine treatment induces the CYP3A4 catalysed sulphoxidation of
      omeprazole, but has no or less effect on hydroxylation via CYP2C19.
AB  - AIMS: Omeprazole has been shown previously to be metabolized by the two
      cytochrome P450 isoforms CYP2C19 (hydroxylation) and CYP3A4 (sulphoxidation). The
      objective of this study was to test the inducibility of these enzymes by
      carbamazepine (CBZ). METHODS: Omeprazole was given as a single oral dose before
      and after 3 weeks of treatment of five patients with CBZ (400-600 mg daily).
      RESULTS: Mean area under the plasma concentration vs time curve (AUC) between 0
      and 8 h after drug intake, decreased by about 40% for omeprazole and its hydroxy
      metabolite and increased for its sulphone metabolite, but the changes were not
      statistically significant. The ratio of the AUCs of omeprazole and its sulphone,
      used as an index of CYP3A4 activity, decreased in all patients (P = 0.052), while
      there was no change in the omeprazole/hydroxyomeprazole AUC ratio used as an
      index for CYP2C19 activity. There was a significant decrease in the mean ratio of
      the AUC of the hydroxy and sulphone metabolites from 2.58 to 0.93 (P = 0.046)
      with a mean difference of 1.79 (95% CI: 0.07 to 3.50) showing that the induction
      was more pronounced for CYP3A4 than for CYP2C19. CONCLUSIONS: CBZ induces CYP3A4,
      but not, or to a lesser extent, CYP2C19. The induction of the sulphoxidation of
      omeprazole by CBZ seems to have no major clinical implication.

PMID- 9278209
TI  - Differential inhibition of cytochrome P450 isoforms by the protease inhibitors,
      ritonavir, saquinavir and indinavir.
AB  - AIMS: To compare the inhibitory potential of the HIV protease inhibitors
      saquinavir, ritonavir and indinavir against CYP1A2, CYP2C9, CYP2E1 and CYP3A4
      catalysed metabolic reactions in human liver microsomes in vitro. METHODS:
      Microsomes from six human livers were utilized in this study. The probe
      substrates were phenacetin (CYP1A2), tolbutamide (CYP2C9), chlorzoxazone (CYP2E1)
      and testosterone (CYP3A4). Metabolites were analysed by high performance liquid
      chromatography. IC50 (concentration of inhibitor giving 50% decrease in enzyme
      activity) and, where appropriate, K(i) values were calculated. RESULTS: Ritonavir
      was a very potent inhibitor of CYP3A4 mediated testosterone 6beta-hydroxylation
      (mean K(i) = 0.019 +/- 0.004 microM, mean +/- s.d.; n = 6) and also inhibited
      tolbutamide hydroxylation (IC50 = 4.2 +/- 1.3 microM, mean +/- s.d.; n = 6).
      Inhibition of phenacetin O-deethylation and chlorzoxazone 6-hydroxylation was
      negligible. Indinavir was an order-of-magnitude less potent in inhibiting CYP3A4
      (K(i) = 0.17 +/- 0.01 microM) and did not produce appreciable inhibition of the
      CYP1A2, CYP2C9 or CYP2E1 catalysed reactions. Saquinavir was the least potent
      CYP3A4 inhibitor (K(i) = 2.99 +/- 0.87 microM) and produced some inhibition of
      CYP2C9 (approximately 50% at 50 microM). CONCLUSIONS: The HIV protease inhibitors
      have differential effects on CYP isozymes. There is obvious potential for
      clinically significant drug interactions particularly with ritonavir.
      Pharmacokinetic drug interaction studies are crucial to gain an overall
      understanding of the beneficial and potentially harmful effects of this important
      group of drugs.

PMID- 9278210
TI  - Effect of troleandomycin on the pharmacokinetics of imipramine in Chinese: the
      role of CYP3A.
AB  - AIMS: In vitro data indicate that imipramine (IMI), a widely used tricyclic
      antidepressant drug, is N-demethylated by several isoforms of cytochrome P450,
      which include CYP3A4. The aim of this study was to investigate the role of CYP3A
      in the in vivo N-demethylation of IMI. METHODS: Healthy subjects were given
      troleandomycin (TAO), a selective inhibitor of CYP3A, 250 mg daily for 2 days
      before a single oral dose of 100 mg IMI was administered. RESULTS: Pretreatment
      with TAO significantly increased the AUC of IMI by 59% (1971 +/- 938 vs 3134 +/-
      2000 microg l(-1) h, 95% confidence interval for difference between means: 218 to
      2108 microg l(-1) h, P < 0.05) and decreased its oral clearance by 30% (60.9 +/-
      27.4 vs 42.5 +/- 22.7 l h(-1), 95% confidence internal for difference between
      means: 7.2 to 31.7 l h(-1), P < 0.05). CONCLUSIONS: We conclude that CYP3A may
      play an important role in the in vivo N-demethylation of IMI.

PMID- 9278211
TI  - Investigation of multiple dose citalopram on the pharmacokinetics and
      pharmacodynamics of racemic warfarin.
AB  - AIMS: An open, controlled, randomized, crossover study was conducted in healthy
      males to assess the possible occurrence of a pharmacokinetic/pharmacodynamic
      interaction between warfarin and the selective serotonin re-uptake inhibitor
      citalopram. METHODS: Twelve subjects received a single 25 mg dose of racemic
      warfarin either alone or on Day 15 of a 21-day oral dosing regimen of 40 mg
      citalopram daily. Blood samples for pharmacokinetic analysis were obtained over a
      168 h period after warfarin dosing. The degree of anticoagulation was assessed by
      the prothrombin time. RESULTS: Citalopram produced no change in the
      pharmacokinetics of (R)- and (S)-warfarin, indicating that citalopram does not
      alter the metabolism of warfarin mediated via CYP1A2, CYP3A4 and CYP2C9.
      Citalopram coadministration resulted in a statistically significant increase in
      the maximum prothrombin time (R(max); by 1.6 +/- 3.0 s) and the area under the
      prothrombin time-time curve (AUC(PT); by 5.0 +/- 5.7%). The 90% confidence
      intervals for R(max) and AUC(PT) ratios (citalopram + warfarin/warfarin alone)
      were 1.01-1.10 and 1.03-1.07, respectively. CONCLUSIONS: The small increase in
      prothrombin time observed in this study with coadministration of citalopram and
      warfarin is not considered to be of importance in the clinical setting.

PMID- 9278212
TI  - Erythropoietin production in healthy volunteers subjected to controlled hypobaric
      hypoxia: further evidence against a role for adenosine.
AB  - AIMS: Objective of this study was to investigate whether adenosine modulates
      renal erythropoietin production. METHODS: In the present study erythropoietin
      production was stimulated by hypobaric hypoxia by subjecting healthy volunteers
      to a simulated altitude of 4000 m in a low pressure chamber for 5.5 h. During
      exposure to hypoxia the subjects received i.v. in a randomized, single-blind,
      cross-over fashion the non-specific adenosine antagonist theophylline, the
      adenosine reuptake inhibitor dipyridamole and placebo. RESULTS: Contrary to the
      working hypothesis, theophylline did not decrease and dipyridamole did not
      further boost erythropoietin concentrations. CONCLUSIONS: The results are in
      agreement with our earlier study using haemorrhage as a controlled physiological
      stimulus of erythropoietin production, and would question a major role for
      adenosine as a mediator of renal erythropoietin production.

PMID- 9278213
TI  - The effect of age on plasma MEGX concentrations.
AB  - AIMS: The study was designed to assess the effect age on the
      monoethylglycinexylidide (MEGX) liver function test. METHODS: Plasma MEGX
      concentration was measured in 16 young and 17 elderly healthy volunteers 10, 15,
      30, 45 and 60 min after intravenous injection of 1 mg kg(-1) lignocaine. RESULTS:
      Lower MEGX concentrations were noted in elderly subjects. The difference between
      young and old individuals became increasingly significant as the sampling time
      was increased, mainly because of a progressive decrease in intersubject
      variability within each of the two study groups. Linear regression analysis
      consistently showed that the strength of the relationships between MEGX
      concentration and age increased with increased sampling time and was maximal at
      60 min (r = -0.70; P < 0.0001; reduction in MEGX formation (95% CI) 0.51 (0.33
      0.69) ng ml(-1) per year). CONCLUSIONS: These data indicate that the rate of MEGX
      production declines significantly with age. Therefore, when the results of the
      MEGX test are to be compared in different study groups, subjects should be
      strictly matched for age.

PMID- 9278214
TI  - Captopril has no significant scavenging antioxidant activity in human plasma in
      vitro or in vivo.

PMID- 9278215
TI  - Fluvoxamine in breast-milk and infant development.

PMID- 9278216
TI  - Ibuprofen in human milk.

PMID- 9278217
TI  - Pharmacokinetics of inhaled drugs.

PMID- 9278218
TI  - Host genetic factors influencing the outcome of hepatitis.
AB  - A strong genetic component determining the outcome of hepatitis B virus (HBV)
      infection has been established through twin studies. The immunopathogenesis of
      HBV infection is well described and it has therefore been possible to predict
      some gene loci, exhibiting polymorphism, may influence the outcome of HBV
      infection. As expected, the immune response genes in the major histocompatibility
      complex (MHC) on the short arm of chromosome 6 have provided confirmed
      susceptibility genes. In hepatitis C virus (HCV) infection the picture is not so
      clear although comparison of the known immunological phenomena with those of HBV
      suggest that polymorphisms in the MHC may also influence disease outcome.
      Identification of susceptibility genes, which modify disease phenotype, may
      assist in predicting natural outcome of infection or response to therapy.

PMID- 9278220
TI  - High prevalence of hantavirus infection in a group of Chinese patients with acute
      hepatitis of unknown aetiology.
AB  - In southwestern China, small but substantial numbers of patients with acute
      hepatitis were found without known hepatropic viral infections (hepatitis A, B,
      C, D or E, cytomegalovirus, Epstein-Barr virus) and were receiving no hepatotoxic
      drugs. Prevalence of antibodies, both neutralizing and specific immunoglobulin
      (Ig)M and IgG, to Hantaan virus were evaluated in a cohort of 136 such patients:
      83 were of unknown aetiology, 53 had known viral hepatitis and 59 healthy
      subjects acted as controls. The results showed that the incidence of neutralizing
      antibody to Hantaan virus in acute hepatitis patients with non-hepatitis A-E
      virus infections (13 of 83) was significantly higher than in those with A-E
      infections (0 of 53, P<0.01). Furthermore, the incidence of specific IgM antibody
      to Hantaan virus in acute hepatitis patients with non-hepatitis A-E virus
      infections (6 of 83) was significantly higher than in those with A-E infections
      (0 of 53, P<0.05) and in healthy subjects (0 of 59, P < 0.05). These findings
      suggest that Hantaan virus may be an important agent, contributing, at least in
      southwestern China, to a significant number of the cases of acute hepatitis of
      unknown aetiology. This hantavirus infection resulted in an acute hepatitis,
      differing from the typical diseases: haemorrhagic fever with renal syndrome
      (HFRS) and hantavirus pulmonary syndrome (HPS).

PMID- 9278219
TI  - Functional implications of hepatitis B surface antigen (HBsAg) in the T cells of
      chronic HBV carriers.
AB  - This study was undertaken to investigate the role of T-lymphocyte-derived soluble
      factors in the maintenance of the hepatitis B virus (HBV) chronic carrier state.
      Cell-free supernatants from the peripheral blood T lymphocytes of chronic HBV
      carriers were produced by incubating them for 48 h in tissue culture medium.
      These supernatants were added to in vitro hepatitis B s antibody (HBsAb)
      producing cultures of peripheral blood mononuclear cells from hepatitis B surface
      antigen (HBsAg) vaccinees stimulated with HBsAg or pokeweed mitogen. T-cell
      supernatants from chronic carriers suppressed in vitro HBsAb antibody synthesis,
      whereas those from control subjects did not. This suppression was antigen
      specific as the supernatants did not suppress synthesis of total IgG or IgM. HBV
      viral sequences were demonstrable, by Southern and dot-blot hybridization, in the
      T cells secreting this factor. We also demonstrated the presence of HBsAg in T
      cell supernatants derived from these cells. These results show that HBsAg of T
      cell origin may have a role in suppressing HBsAb production. Our observations
      point to the role of HBsAg-specific cellular and humoral responses in favouring
      persistence of the chronic HBV carrier state.

PMID- 9278222
TI  - Effects of cirrhosis, interferon and azathioprine on adverse events in patients
      with chronic hepatitis C treated with ribavirin.
AB  - To determine adverse events of ribavirin in the treatment of chronic hepatitis C,
      41 patients (18 with cirrhosis), treated with ribavirin at an initial dose of 600
      1200mg day(-1), were analysed retrospectively (six patients were treated twice
      because adverse effects during the first treatment necessitated cessation of
      ribavirin). Indications for ribavirin included a contraindication (n = 15) an
      intolerance (n = 11) or a non-response (n = 15) to interferon (IFN). Ribavirin
      was combined with IFN 3 million units (MU) three times weekly for 15 patients and
      with azathioprine for six patients (five of whom were transplant patients). No
      cirrhotics and only one patient treated with ribavirin + IFN received
      azathioprine. The mean duration of treatment was 5 months (range 1-18 months).
      Sixteen of 47 treatments (34%) with ribavirin were stopped: four because of
      vomiting (8.5%), two for psychiatric disorder, one for dry cough, one for an
      unrelated cause, and eight (at 1-2 months) because of a fall in the level of
      haemoglobin (Hb) of 4.6 g dl(-1) (range 2.7-5.9 g dl[-1]); however, according to
      the rules of international protocol, we would have expected only four treatments
      (two in patients receiving azathioprine) with Hb < 8.5 g dl(-1) to be stopped.
      The decrease in Hb level occurred more slowly in patients treated with IFN plus
      ribavirin than in patients treated with ribavirin alone and was of lower clinical
      significance in patients with cirrhosis than in patients without cirrhosis. After
      exclusion of patients receiving azathioprine, there was no significant difference
      in the fall of Hb level between cirrhotic and non-cirrhotic patients and between
      patients treated with IFN plus ribavirin and patients treated with ribavirin
      alone. Interestingly, the platelet count of patients treated with IFN plus
      ribavirin fell less than in patients treated with IFN alone. The most important
      and expected adverse event associated with ribavirin was haemolysis. Anaemia <
      8.5 g dl(-1), requiring cessation of ribavirin therapy, was present in 9% of
      patients and was worsened by azathioprine. Abdominal discomfort and dry cough
      were other, potentially important, clinical adverse events found in our study.

PMID- 9278221
TI  - Preoperative serum levels of wild-type and hepatitis B e antigen-negative
      hepatitis B virus (HBV) and graft infection after liver transplantation for HBV
      related hepatocellular carcinoma.
AB  - Allograft infection in hepatitis B surface antigen (HBsAg)-positive patients
      undergoing liver transplant (OLT) is still significant, despite post-transplant
      prophylaxis with high doses of immunoglobulin to HBsAg. Baseline status and post
      OLT levels of viraemia and wild-type and hepatitis B e antigen (HBeAg)-negative
      hepatitis B virus (HBV) were correlated with the clinical course of 16
      consecutive HBsAg carriers. positive for hepatitis B e antibody, with
      hepatocellular carcinoma who underwent OLT and received permanent post-OLT
      prophylaxis with antibody to HBsAg (HBsAb). Fourteen patients had less than 10(3)
      HBV genome equivalents ml(-1) (eq ml[-1]) at baseline and remained HBV free after
      a median of 36 months following OLT. Two patients with mean pre-OLT viraemia
      higher than 10(5) genome eq ml(-1) and prevalent HBeAg-negative HBV viraemia
      before OLT suffered a severe graft hepatitis. Interferon-alpha2b (3 MU m(-2) per
      day) was able to reduce viraemia in both patients and to revert the clinical
      course of the infection in one, who remained infection-free 22 months after IFN
      treatment. Fourteen patients had less than 10(3) HBV genome eq ml(-1) at baseline
      and remained HBV free, after a median of 36 months following OLT, with permanent
      HBsAb immunoprophylaxis. These observations suggest that the quantitative
      analysis of HBV pre-OLT viraemia levels may provide a very useful tool for
      predicting the ideal time of liver replacement. Clinical trials on the use of
      antiviral drugs capable of inhibiting HBV serum levels before liver
      transplantation should be pursued on this premise.

PMID- 9278223
TI  - Importance of age in chronic hepatitis C virus infection.
AB  - This study was designed to investigate the value of liver biopsy in the
      management of patients with chronic hepatitis C virus infection and to identify
      risk factors for fibrosis. It was a prospective audit of clinical, biochemical,
      virological and radiological features for predicting liver fibrosis in 140
      consecutive patients seropositive for antibody against hepatitis C virus. Seventy
      five per cent of patients were asymptomatic and 69% had no clinical signs of
      chronic liver disease. Serum transaminase levels were normal in 44% of patients,
      less than twice normal in 35% and more than twice normal in 21%. Ultrasound scan
      was unremarkable in 85%. Sixty-nine per cent of patients were viraemic at the
      time of liver biopsy. Liver histology revealed that fibrosis was absent in only
      10% of patients (stage 0) while cirrhosis was evident in 7% (stage 5). Liver
      fibrosis was detected in 90% of patients (stage 1, 11%; stage 2, 41%; stage 3,
      21%; and stage 4, 10%). Univariate analysis showed that increasing age, clinical
      signs of chronic liver disease and abnormal ultrasound scan findings were
      associated with liver fibrosis (P<0.05); however, multiple linear regression
      analysis of all the clinical features did not reveal a useful model (sensitivity
      42% and specificity 23%) for predicting liver fibrosis. Hence, no combination of
      clinical, biochemical, virological or radiological data was reliable in
      discriminating the stage of liver fibrosis in patients with chronic hepatitis C
      virus infection. However, older patients, especially those with clinical signs of
      chronic liver disease and abnormal ultrasound scan findings, were more likely to
      have advanced fibrosis. We recommend liver biopsy as the single most important
      investigation in detecting liver fibrosis.

PMID- 9278224
TI  - Quantitative assessment of serum hepatitis B e antigen, IgM hepatitis B core
      antibody and HBV DNA in monitoring the response to treatment in patients with
      chronic hepatitis B.
AB  - Virological response to treatment of chronic hepatitis B is defined as the loss
      of serum hepatitis B virus DNA (HBV DNA) and hepatitis B e antigen (HBeAg). The
      quantitative measurement of HBV DNA is useful for monitoring and predicting the
      response to therapy with interferon-alpha (IFN-alpha). In this study, we
      evaluated whether quantitative measurement of serum HBeAg and IgM antibody to
      hepatitis B core antigen (HBcAb) could also be used in this manner. Using a
      microparticle-capture enzyme immunoassay (IMx), a standard curve of fluorescence
      rate vs HBeAg concentration was constructed to provide quantitative results. The
      IgM HBcAb index was also measured using a microparticle enzyme immunoassay and
      serum HBV DNA was measured by a solution hybridization assay. We studied 48
      patients who were initially positive for HBeAg and HBV DNA and who were treated
      with IFN-alpha2b. Their sera were serially evaluated for HBeAg concentration, and
      results were compared with HBV DNA levels. In the 14 patients who responded to
      IFN, similar disappearance curves were observed with good intraindividual
      correlation between the levels of the two markers. In the 34 non-responders,
      HBeAg levels decreased during treatment but never became negative; HBV DNA levels
      also decreased during treatment and became transiently undetectable in six
      patients, falsely suggesting treatment success. The IgM HBcAb index paralleled
      changes in alanine aminotransferase (ALT) concentration and did not provide
      additional information. Multiple logistic regression indicated that baseline ALT
      and HBeAg concentrations were independent predictors of the response to treatment
      and the addition of neither HBV DNA nor IgM HBcAb improved the model. We conclude
      that quantitative measurement of HBeAg provides information similar to that of
      HBV DNA in monitoring and predicting the response to treatment; this technique
      could be readily adaptable to clinical laboratories.

PMID- 9278225
TI  - Transmission routes and clinical courses in sporadic acute hepatitis C.
AB  - Between March 1994 and March 1996 we studied transmission routes and clinical
      courses in eight patients with sporadic acute hepatitis C (two men, six women).
      Of the eight patients, three were treated for another illness 1-2 months before
      the onset of hepatitis, one was a parenteral drug abuser, one had an accidental
      needlestick injury and two had sexual contact with a partner with chronic
      hepatitis C virus (HCV) infection. Clinical courses included four women whose HCV
      RNA and alanine aminotransferase (ALT) became persistently negative without
      treatment, and four men and two women with the same results following interferon
      (IFN) treatment. It is thought that IFN therapy may prevent the progression to
      chronic liver disease. Results from this study might be useful in the future
      management of patients with sporadic acute hepatitis C.

PMID- 9278226
TI  - Antibody to hepatitis E virus in HIV-infected individuals and AIDS patients.
AB  - Antibody to hepatitis E virus of IgG class (anti-HEV IgG) is regularly detected
      in industrialized countries, where HEV is non-endemic, at levels not exceeding 2
      3%; seropositive individuals are often found in certain groups of patients and
      professionals exposed to an increased risk of blood-borne infections. The present
      study was aimed at the identification of anti-HEV IgG in patients with human
      immunodeficiency virus (HIV) infection, including acquired immune deficiency
      syndrome (AIDS), living in Russia and Belarus, an area of low anti-HEV prevalence
      with a moderate spread of HIV infection and AIDS. In Russia, 13 out of 117 HIV
      infected patients (11.1%) were found to be anti-HEV seropositive. This differed
      significantly from the frequency observed in the normal population (1.7%) but not
      from the frequency in a matching control, high-risk group consisting of male
      prisoners (8.0%). No difference in the frequency of anti-HEV IgG seropositivity
      was found between groups of HIV-infected men subdivided by sexual orientation.
      The rate of anti-HEV seropositivity increased with the progression of HIV
      infection, reaching 43.3% in AIDS patients and 38.1% in those who died from AIDS.
      In Belarus, anti-HEV IgG seropositivity was not found among 20 HIV-infected
      subjects nor among individuals from the control risk group, which consisted of 25
      intravenous drug users. In conclusion, HEV infection may have common transmission
      mechanisms (risk factors) with HIV infection rather than represent an additional
      opportunistic infection in AIDS.

PMID- 9278227
TI  - DNA transfer into vascular smooth muscle using fusigenic Sendai virus (HVJ)
      liposomes.
AB  - Manipulation of the genetic machinery of cells both in vitro and in vivo is
      becoming an ever more important means of elucidating pathways of molecular and
      cellular biochemistry. In addition, gene therapy has been proposed as a novel and
      potentially powerful treatment for both inherited and acquired diseases.
      Successful gene transfer and gene blockade generally depend on high efficiency
      delivery of exogenous DNA or RNA into living cells, and much effort has therefore
      been focused on the development of methods for achieving this delivery in a safe
      and effective manner. We describe here our application of fusigenic Sendai virus
      (HVJ)-liposome technology toward the effective delivery of DNA into vascular
      smooth muscle cells (VSMC) in cell culture. Cellular uptake and intracellular
      distribution of oligodeoxynucleotide (ODN) after transfection with HVJ-liposome
      complexes was characterized using fluorescent (FITC)-labeled ODN, and the
      biologic effect of HVJ-liposome mediated transfection was demonstrated via
      inhibition of DNA synthesis in cultured VSMC using antisense ODN against basic
      fibroblast growth factor.

PMID- 9278229
TI  - Retroviral techniques for studying organogenesis with a focus on heart
      development.
AB  - The study of development has been revolutionized by the application of molecular
      techniques, which make it possible to identify factors involved in the
      developmental process. However, in order to correctly assess the contribution of
      these growth factors, transcription factors, receptors or signaling molecules, it
      is necessary to study them in the animal as a whole; it is not enough to conclude
      that they must be important based on their expression patterns.

PMID- 9278228
TI  - Adenovirus mediated-gene transfer into cardiomyocytes.
AB  - To circumvent limitations imposed by conventional gene transfer techniques into
      cardiac muscle cells, we studied whether replication defective adenovirus would
      obviate this limitation to basic studies of signal transduction and
      transcriptional control processes in the heart. We demonstrate here the utility
      of adenovirus mediated gene transfer to introduce foreign DNA into post-mitotic
      terminally differentiated ventricular myocytes with uniformity and high
      efficiency. We also provide evidence for the genetic modification of neonatal
      ventricular myocytes by adenovirus early region 1 (E1) proteins and their impact
      on cardiac gene transcription and DNA synthesis respectively. Thus, for studies
      of transcriptional control processes in the heart, which until now have been
      restricted to neonatal ventricular myocytes; adenovirus mediated gene transfer
      provides a means to genetically manipulate adult cardiac muscle cells. The advent
      of adenovirus gene transfer will extend our understanding of the molecular
      mechanisms that mediate basic cardiac disease and may ultimately provide a means
      to therapeutically mitigate the disease process.

PMID- 9278230
TI  - Novel methods for adenovirus-mediated gene transfer to blood vessels in vivo.
AB  - Adenovirus-mediated gene transfer is a promising method for studies of vascular
      biology and potentially for gene therapy. Intravascular approaches for gene
      transfer to blood vessels in vivo generally require interruption of blood flow
      and have several limitations. We have used two alternative approaches for gene
      transfer to blood vessels in vivo using perivascular application of vectors.
      First, replication-deficient adenovirus expressing nuclear-targeted bacterial
      beta-galactosidase was injected into cerebrospinal fluid via the cisterna magna
      of rats. Leptomeningeal cells over the major arteries were efficiently
      transfected, and adventitial cells of large vessels and smooth muscle cells of
      small vessels were occasionally stained. When viral suspension was injected with
      the rat in a lateral position, the reporter gene was expressed extensively on the
      ipsilateral surface of the brain. Thus, adenovirus injected into cerebrospinal
      fluid provides gene transfer in vivo to cerebral blood vessels and, with greater
      efficiency, to perivascular tissue. Furthermore, positioning of the head may
      'target' specific regions of the brain. Second, vascular gene delivery was
      accomplished by perivascular injection of virus in peripheral vessels. Injection
      of the adenoviral vector within the periarterial sheath of monkeys resulted in
      gene transfer to the vessel wall that was substantial in magnitude although
      limited to cells in the adventitia. Approximately 20% of adventitial cells
      expressed the transgene, with no gene transfer to cells in the intima or media.
      These approaches may provide alternative approaches for gene transfer to blood
      vessels, and may be useful for studies of vascular biology and perhaps vascular
      gene therapy.

PMID- 9278231
TI  - Use of a hammerhead ribozyme with cationic liposomes to reduce leukocyte type 12
      lipoxygenase expression in vascular smooth muscle.
AB  - Chemically synthesized hammerhead-type ribozymes targeted against the porcine
      leukocyte-type 12-lipoxygenase (LO) have been developed and studied. One chimeric
      ribozyme consists of DNA in the non-enzymatic portions, and RNA in the enzymatic
      core as well as two phosphorothioate internucleotide linkages at 3' terminus. The
      second ribozyme consists of ribonucleotide sequences generated by in vitro
      transcription. In this chapter we describe methodologies to first analyze the
      ribozyme catalytic activity in vitro by studying cleavage of target RNA in vitro.
      The subsequent sections will describe how to target the catalytic ribozyme and
      deliver it to porcine vascular smooth muscle cells (PVSMC) by a liposome-mediated
      method. Finally ways to evaluate its activity to inhibit expression of the 12-LO
      mRNA will be presented. These results demonstrate the feasibility of using
      ribozymes as novel candidates for therapeutic agents to block specific gene
      expression in vascular cells.

PMID- 9278233
TI  - Identification of proteins that interact with a protein of interest: applications
      of the yeast two-hybrid system.
AB  - The yeast two-hybrid system is a molecular genetic test for protein interaction.
      Here we describe a step by step procedure to screen for proteins that interact
      with a protein of interest using the two-hybrid system. This process includes,
      construction and testing of the bait plasmid, screening a plasmid library for
      interacting fusion proteins, elimination of false positives and deletion analysis
      of true positives. This procedure is designed to allow investigators to identify
      proteins and their encoding cDNAs that have a biologically significant
      interaction with your protein of interest.

PMID- 9278232
TI  - Immunodetection of activated mitogen-activated protein kinase in vascular
      tissues.
AB  - Mitogen-activated protein kinase (MAPK) is a key modulator of cytoplasmic-nuclear
      signal transmission, and for this reason measurement of MAPK activity has become
      very popular. Monitoring of MAPK activity may be particularly relevant to the
      cardiovascular system where it has already been shown that the stimulation of
      cardiomyocytes and smooth muscle cells by stretch and by growth factors activates
      MAPK. Since both growth factors and mechanical stress are causal agents for
      certain pathologies, enhanced MAPK activity may be a good predictor of disease
      progression. A variety of methods have been designed to measure the activation of
      this enzyme including an in vitro assay coupled to either gel electrophoresis or
      binding to P81 paper, an activity gel assay to detect p42/44 isoforms and, more
      recently, monitoring MAPK phosphorylation using immunoblot detection. The
      validity of the latter method is based on the correlation between MAPK activity
      and the degree of phosphorylation. The antibodies have also been of use in the
      detection of MAPK translocation in cell monolayers. In this report, we discuss
      the advantages and disadvantages of all MAPK detection methods and demonstrate an
      additional application for the MAPK antibodies using an in vitro restenosis
      model. In addition, the utility of MAPK measurements to smooth muscle
      pathophysiology and vascular injury (as a predictor of injury) has been assessed.

PMID- 9278234
TI  - Construction of a human heart cDNA library and identification of cardiovascular
      based genes (CVBest).
AB  - The availability of high quality cDNA libraries is often crucial to the
      successful identification and characterization of genes. The concepts and
      potential pitfalls of constructing cDNA libraries are presented. Various
      applications requiring high quality cDNA libraries are outlined, including large
      scale single pass sequencing of cDNA clones to generate expressed sequence tags
      (ESTs) and differential screening of cDNA libraries. The usefulness of combining
      such approaches for the discovery of novel disease-related and cardiovascular
      based ESTs (CVBest) is discussed.

PMID- 9278235
TI  - Competitive RT-PCR for studying gene expression in micro biopsies.
AB  - The technique of RT-PCR has become a powerful method for studying gene expression
      in various species and tissues. Here we present a competitive PCR for
      quantitative measurement of absolute levels of mRNA molecules for the regulatory
      alpha 2/delta subunit of the high-voltage-activated dihydropyridine sensitive
      human cardiac L-type calcium channel. With the method described the dynamic
      process of cardiac gene expression can be studied in human endomyocardial
      biopsies in different patient collectives and even in the individual.

PMID- 9278236
TI  - The nuclear membrane integrity assay.
AB  - A novel technique is described for the evaluation of membrane integrity in
      isolated nuclei. Membrane integrity is assessed by measuring nuclear fragility in
      response to high salt conditions. Salt-induced disruption of the nuclear membrane
      is followed by spectrophotometric monitoring of released nucleotides. The assay
      is based on determining the amount of salt necessary to induce release of 50% of
      the total pool of releasable nucleotides. This allows semiquantitative comparison
      of relative nuclear membrane strength or integrity of different samples in
      response to high salt conditions. In this manner, the effects of altered nuclear
      membrane composition or metabolism on membrane integrity may be monitored.

PMID- 9278237
TI  - Transfer of macromolecules into living adult cardiomyocytes by microinjection.
AB  - Among techniques commonly used to deliver bioactive molecules into living cells,
      microinjection is a very efficient method. Microinjection has been used
      extensively for gene transfer into different cell types. We applied the
      microinjection technique to the adult rat ventricular cardiac muscle cells (AVC)
      in primary culture and optimized microinjection parameters and the appropriate
      cell culture conditions. We also optimized the use of particular agents (i.e. 2,3
      butanedione monoxime, verapamil) for the prevention of the cell damage caused by
      the micropuncture. We obtained the expression of a CMV-beta-galactosidase
      reporter gene in up to 20% of the injected cells with efficient maintenance of
      long term cell viability. Under our experimental conditions direct microinjection
      is a very advantageous technique to transfer macromolecules into living adult
      cardiac muscle cells and a powerful system to study and manipulate the
      biochemistry and molecular biology of the cardiac myocyte.

PMID- 9278238
TI  - Differential display: identifying genes involved in cardiomyocyte proliferation.
AB  - An estimated 15,000 different mRNA species are expressed in a typical mammalian
      cell. The differential expression of mRNAs in both a temporal and cell-specific
      manner determines the fate of the cell and creates the organism. Analysis of this
      differential gene expression has become a central aim of many laboratories
      attempting to understand the mechanisms underlying various biological processes.
      Currently, we are using a technique called differential display to analyze the
      differential expression of genes in cardiomyocytes. Differential display is a
      rapid and powerful technique that was introduced by Liang and Pardee in 1992.
      Since that time, it has been successfully applied by several groups, and it is
      quickly becoming a standard method for studying differential gene expression.
      Here, we present a detailed article discussing the differential display
      methodology and how we have utilized it to identify potential genes involved in
      cardiomyocyte proliferation. Furthermore, we have provided a list of materials
      and supplied examples of data obtained, in an effort to allow the reader to
      perform the technique with success in their own laboratory.

PMID- 9278239
TI  - Analysis of inositol phosphates in heart tissue using anion-exchange high
      performance liquid chromatography.
AB  - The pathways of release and metabolism of inositol phosphates in intact heart
      tissue are different from those observed in isolated cardiomyocytes in culture.
      Thus, it is essential that methods are available for the quantitation of inositol
      phosphates in intact tissue preparations. This manuscript describes methods which
      allow the quantitation of inositol phosphates in different heart preparations
      including isolated atria and intact perfused heart. The availability of such
      methods should facilitate study of the role of inositol phosphates in cardiac
      control mechanisms under physiological and pathological conditions.

PMID- 9278240
TI  - Analysis of phospholipid molecular species.
AB  - A method is described for analysing molecular species of glycerophospholipids.
      Diglycerides obtained by phospholipase C-catalysed hydrolysis of the phospholipid
      are separated into the diacyl- alkylacyl- and alkenylacyl- subclasses by HPLC on
      silicic acid. The molecular species of diacylglycerol are separated by HPLC of
      underivatised diglycerides on a reverse phase octadecyl-silica column.

PMID- 9278241
TI  - Measurements of fatty acid and carbohydrate metabolism in the isolated working
      rat heart.
AB  - The isolated working rat heart is a useful experimental model which allows
      contractile function to be measured in hearts perfused at physiologically
      relevant workloads. To maintain these high workloads the heart is required to
      generate a tremendous amount of energy. In vivo this energy is derived primarily
      from the oxidation of fatty acids. In many experimental situations it is
      desirable to perfuse the isolated working heart in the presence of
      physiologically relevant concentrations of fatty acids. This is particularly
      important when studying energy metabolism in the heart, or in determining how
      fatty acids alter the outcome of myocardial ischemic injury [1, 2]. The other
      major source of energy for the heart is derived from the oxidation of
      carbohydrates (glucose and lactate), with a smaller amount of ATP also being
      derived from glycolysis. Two byproducts of both fatty acid and carbohydrate
      metabolism are H2O and CO2. By labeling the glucose, lactate, or fatty acids in
      the perfusate with 3H or 14C the experimenter can quantitatively collect either
      3H2O or 14CO2 produced by the heart. By using radioisotopes that are labeled at
      specific hydrogen or carbon molecules on the various energy substrates, and by
      knowing the specific activity of the radiolabeled substrate used, it is possible
      to determine the actual rate of flux through these individual pathways. This
      paper will describe the experimental protocols for directly measuring fatty acid
      and carbohydrate metabolism in isolated working rat hearts.

PMID- 9278242
TI  - Fura-2 fluorescent technique for the assessment of Ca2+ homeostasis in
      cardiomyocytes.
AB  - Ca2+ homeostasis plays a pivotal role in maintaining cell growth and function.
      Many heart diseases are related to the abnormalities in Ca2+ mobilization and
      extrusion. Ca2+-sensitive fluorescent dyes have been used successfully to
      estimate intracellular free Ca2+ ([Ca2+]i) level and the mechanisms of Ca2+
      movements in living cells. This article is focused on the methodology involving
      the use of Fura-2/AM or free Fura-2 to measure agonist-induced Ca2+ mobilization
      as well as the mechanisms of changes in [Ca2+]i in cardiomyocytes. Methods
      involving Fura-2 technique for the measurement of Ca2+ extrusion from the cells
      and Ca2+ reuptake by sarcoplasmic reticulum (SR) are also described. The
      prevention of KCl-induced increase in the intracellular Ca2+ is shown by
      chelating the extracellular Ca2+ with EGTA or by the presence of Ca2+-channel
      inhibitors such as verapamil and diltiazem. The involvement of SR in the ATP
      induced increase in intracellular Ca2+ is illustrated by the use of Ca2+-pump
      inhibitors, thapsigargin and cyclopiazonic acid as well as ryanodine which
      deplete the SR Ca2+ storage. The use of 2-nitro-4-carboxyphenyl N,N-diphenyl
      carbamate (NCDC), an inhibitor of inositol 1,4,5-trisphosphate (IP3) production,
      is described for the attenuation of phosphatidic acid (PA) induced increase in
      Ca2+-mobilization. The increase in intracellular Ca2+ in cardiomyocytes by PA,
      unlike that by KCl or ATP, was observed in diabetic myocardium. Thus, it appears
      that the Fura-2 method for the measurement of Ca2+ homeostasis in cardiomyocytes
      is useful in studying the pathophysiology and pharmacology of Ca2+ movements.

PMID- 9278243
TI  - Spectroscopic determination of sarcoplasmic reticulum Ca2+ uptake and Ca2+
      release.
AB  - In this report we describe the application of spectroscopic methods to the study
      of Ca2+ release by isolated native sarcoplasmic reticulum (SR) membranes from
      rabbit skeletal muscle. To date, dual-wavelength spectroscopy of arsenazo III and
      antipyrylazo III difference absorbance have been the most common spectroscopic
      methods for the assay of SR Ca2+ transport. The utility of these methods is the
      ability to manipulate intraluminal Ca2+ loading of SR vesicles. These methods
      have also been useful for studying the effect of both agonists and antagonists
      upon SR Ca2+ release and Ca2+ uptake. In this study, we have developed the
      application of Calcium Green-2, a long-wavelength excitable fluorescent
      indicator, for the study of SR Ca2+ uptake and release. With this method we
      demonstrate how ryanodine receptor Ca2+ channel opening and closing is regulated
      in a complex manner by the relative distribution of Ca2+ between extraluminal and
      intraluminal Ca2+ compartments. Intraluminal Ca2+ is shown to be a key regulator
      of Ca2+ channel opening. However, these methods also reveal that the intraluminal
      Ca2+ threshold for Ca2+-induced Ca2+ release varies as a function of extraluminal
      Ca2+ concentration. The ability to study how the relative distribution of a
      finite pool of Ca2+ across the SR membrane influences Ca2+ uptake and Ca2+
      release may be useful for understanding how the ryanodine receptor is regulated,
      in vivo.

PMID- 9278245
TI  - A simple method for preparation of cultured cardiac fibroblasts from adult human
      ventricular tissue.
AB  - Cardiac fibroblasts constitute greater than 90% of non-myocyte cells in the
      heart. Because they are responsible for synthesis of components of the
      extracellular matrix, growth factors and cytokines in the myocardium, they play
      an important role in normal and pathologic performance of the heart. An
      understanding of their biology requires in depth studies in a stable and reliable
      system in which the biological responses of cardiac fibroblasts to various
      stimuli can be determined. With the exception of few, all studies have been
      performed on cardiac fibroblasts obtained from rodent hearts. We present a method
      for isolation and subsequent culture of viable cardiac fibroblasts from
      ventricular tissue of adult human. This method allows rapid and reliable
      isolation and subsequent culture of cardiac fibroblasts from adult heart tissue
      without the need for cumbersome isolation techniques and complex nutrient
      enriched and hormone-supplemented culture media for maintenance.

PMID- 9278244
TI  - The use of confocal microscopy in the investigation of cell structure and
      function in the heart, vascular endothelium and smooth muscle cells.
AB  - In recent years, fluorescence microscopy imaging has become an important tool for
      studying cell structure and function. This non invasive technique permits
      characterization, localisation and qualitative quantification of free ions,
      messengers, pH, voltage and a pleiad of other molecules constituting living
      cells. In this paper, we present results using various commercially available
      fluorescent probes as well as some developed in our laboratory and discuss the
      advantages and limitations of these probes in confocal microscopy studies of the
      cardiovascular system.

PMID- 9278247
TI  - Potent and selective gene inhibition using antisense oligodeoxynucleotides.
AB  - The development of antisense technology as a generally useful tool relies on the
      use of potent agents and the utilization of many controls in experiments. Here we
      describe our experience using oligodeoxynucleotides (ODNs) containing C-5
      propynyl pyrimidine and phosphorothioate modifications as broadly applicable gene
      inhibition agents in cell culture. Methods include selection of antisense
      sequences, synthesis and purification of ODNs, choice of controls, delivery
      methods (microinjection, cationic lipid transfection, and electroporation), and
      analysis of gene inhibition.

PMID- 9278246
TI  - DNA antisense strategies in the study of receptors for vasoactive peptides, and
      of growth and wound-healing factors.
AB  - Antisense oligodeoxynucleotide technology has contributed greatly to the overall
      understanding of both mRNA stability as well as translational processes leading
      to protein synthesis. Arrest of translational processes by DNA antisense strands
      usually reduces maximal effects of agonists without affecting their apparent
      affinities in treated isolated vascular or nonvascular preparations. In the
      present study, examples are given of DNA antisense oligonucleotide-induced
      repression of receptors for endothelins, kinins as well as of the platelet
      derived growth factor. Furthermore, the efficiency of this technology illustrates
      the roles of protooncogenes (c-myc and c-myb) in wound-healing mechanisms. The
      overall mechanism of action of these oligomers is described and the relevance of
      size, chemical alterations and mode of delivery are illustrated. Release of
      oligophosphorothioates from polymer matrices and gels can produce a prolonged
      effect in vivo. Antisense oligonucleotides remain essential in experimental
      models for which receptor antagonists or selective inhibitors of intracellular
      components are currently unavailable.

PMID- 9278248
TI  - Immunohistochemical analysis of the adaptation of adult guinea-pig cardiomyocytes
      in long-term cultures and in cocultures with cardiac neurons: a novel model for
      studies of myocardial function.
AB  - In this study, we used laser confocal scanning microscopy and immunofluorescent
      markers to describe the establishment of long-term cultures of adult guinea-pig
      cardiomyocytes and their cocultures with adult intrinsic cardiac neurons. We have
      also investigated the effect of plating density on the adaptation of the myocytes
      in culture. Providing that the preparation of freshly isolated cardiomyocytes
      consists mostly (> 80%) of rod-shaped, Ca-tolerant, and quiescent cells and these
      are plated under optimal conditions and density (10(5)/cm2), these myocytes have
      the following characteristics: (1) they remain elongated with regular
      ultrastructural characteristics and quiescent for several days; (2) within 10-14
      days, they reestablish their intercellular contacts and resume contractile
      activity, which becomes synchronous all through the confluent layers; (3) they
      retain their regular myofibrilar striation all through the adaptation to culture
      conditions without any sign of dedifferentiation or redifferentiation; (4) these
      characteristics are lost when the cells are plated at too low (< 10(4)/cm2) or
      too high (2 x 10(5)/cm2) a density and they exhibit signs of dedifferentiation;
      (5) the adult ventricular myocytes appear to retain their ability to express
      atrial natriuretic peptide (ANP), as indicated by immunoreactivity to anti-ANP
      antibody; (6) this activity seems to be directly related to the surface area of
      the myocytes in contact with the substrate (i.e. to the 'stretch' of the
      myocytes); (7) the intrinsic cardiac neurons grow intricate networks of neurites,
      which form a free-ending type of contact with the cocultured myocytes. Long-term
      cultures of adult guinea-pig ventricular myocytes, alone or in their cocultures
      with cardiac neurons in which both are fully active functionally, provide a
      valuable experimental model which opens new possibilities for studying the
      cellular and molecular regulation of myocardial function under acute or chronic
      effects of various intrinsic and/or extrinsic factors, including neuroregulation.

PMID- 9278249
TI  - Heterogeneity in buffalo pituitary prolactin.
AB  - The Ellis procedure of serial extraction of gonadotropins and growth hormone (GH)
      followed by alkaline ethanol extraction was adopted to process freshly frozen
      buffalo pituitaries. The procedure after slight modification was found very
      useful as more than 2 mg of GH free immunoreactive prolactin (PRL) could be
      isolated from each gram of wet pituitary tissue. Further, the biochemical purity
      and immunobiological potency of the extracted PRL, designated as P-I, was
      comparable with that of the highly purified samples of homologous and
      heterologous PRLs. No non-PRL protein was detectable in P-I. Micro-heterogeneity
      with regard to size, charge, co- and post-translational modifications was also
      investigated under different conditions of extraction and at different stages of
      purification. Immunological and biological potencies were compared in homologous
      competitive enzyme linked immunosorbent assay (ELISA) developed for buffalo PRL
      and in rat Nb2 lymphoma proliferation assay respectively. Structural
      heterogeneity was observed in all the preparations checked including fresh
      pituitary homogenate and highly purified hormone. Nevertheless a 25 K species
      corresponding to the hormone monomer was always the only paramount form
      comprising more than 90% of the total PRL protein in all the samples including P
      I. Similar size forms were observed in all preparations and were found to be
      equivalents of monomers, dimers, covalent-and non-covalent multimers, disulphide
      bridged forms and cleaved fragments. Other sibling species identified were
      glycosylated PRL, charge isoforms and forms that perhaps differed in their
      extractability from the pituitary tissue. Strong apparent size heterogeneity was
      displayed by the monomeric buffalo PRL. In light of these observations and the
      information on the structural and functional significance and the consequences of
      polymeric forms, the use of a heterogeneous PRL (P-I) as a reference hormone is
      recommended for a valid assay.

PMID- 9278250
TI  - Effect of lipoprotein-X on lipid metabolism in rat kidney.
AB  - Lipoprotein-X (Lp-X) is found in the plasma of patients with familial lecithin:
      cholesterol acyltransferase (LCAT) deficiency syndromes. The majority of the
      patients with this disorder develop progressive glomerulosclerosis. In this
      study, the effect of Lp-X on lipid metabolism in perfused rat kidney was
      investigated. Lp-X was isolated from plasma of patients with familial LCAT
      deficiency by sequential ultracentrifugation and gel filtration column
      chromatography. Rat kidneys were perfused for 1-2 h with Krebs-Henseleit buffer
      containing 20 microM [1-(14)C]acetate or 20 microM [Me-3H]choline. In the
      presence of Lp-X, no significant difference in the incorporation of radioactivity
      into triglycerides, cholesterol, phosphocholine, CDP-choline and sphingomyelin
      was observed. However, incorporation of radioactivity into cholesteryl esters and
      phosphatidylcholine was significantly elevated in Lp-X perfused kidneys. The
      contents of cholesterol, cholesteryl esters and phosphatidylcholine were also
      significantly increased in Lp-X perfused kidneys. The increase in lipid content
      in the Lp-X perfused kidney is attributed to the direct deposition of Lp-X lipids
      into the organ. The increase in the labelling of cholesteryl esters was
      attributed to the increase of available substrate (cholesterol) for the acyl
      CoA:cholesterol acyltransferase (ACAT) reaction. The increase in
      phosphatidylcholine labelling was caused by a reduced turnover of the newly
      synthesized labelled phosphatidylcholine during Lp-X perfusion.

PMID- 9278252
TI  - Vitamins Q and E, extracorporal circulation and hemolysis.
AB  - Whole blood vitamin Q (ubiquinone), plasma vitamins Q and E (alpha-(alpha
      )tocopherol) and free cholesterol (FC) were studied before (control or base-line
      value, sample I) and during open chest surgery and extracorporal circulation
      (samples II-IV) in 10 male IHD patients. Identity existed between control whole
      blood and plasma ubiquinone. During surgery an increased discrepancy with lower
      plasma vitamin Q levels were seen. Control plasma vitamins Q, E and FC averaged
      0.88 +/- 0.16 (SE), 12.1 +/- 2.2 mg x l(-1) and 0.75 +/- 0.15 g x l(-1).
      Corresponding molar values were 1.02 +/- 0.17, 28.1 +/- 5.1 micromol x l(-1) and
      1.94 +/- 0.74 mmol x l(-1). Vitamin Q and E decreased continuously and averaged
      0.64 mg x l(-1) in sample IV (0.74 micromol x l(-1), p < 0.001) and 9.4 mg x l(
      1) in sample III (21.8 micromol x l(-1), p < 0.001). Hemolysis in all sample IV
      vials, ruined all vitamin E determinations. When normalized for FC (NQ and NE),
      decreases were found to be 17 (IV) and 12% (III), respectively. Large
      interindividual variations existed. High control NQ and NE values allowed a
      larger antioxidant vitamin depletion. High NQ seemed also to be a prerequisite
      for NE depletion. In addition, signs indicated an active liver vitamin Q release
      for patients rich in control antioxidant values. It was suggested that the
      antioxidant vitamin depletion did not prevent from radical trauma to membrane
      structural lipids (especially omega-3 fatty acids or vitamin F1), less membrane
      fluidity, erythrocyte fragility and hemolysis.

PMID- 9278251
TI  - Glycosylation of asparagine 24 of the natriuretic peptide receptor-B is crucial
      for the formation of a competent ligand binding domain.
AB  - UV cross-linking studies of the natriuretic peptide receptor-B (NPR-B) using
      radiolabeled C-type natriuretic peptide (CNP) indicate that only fully
      glycosylated receptors are capable of binding ligand. We therefore used site
      directed mutagenesis to determine which potential glycosylation sites are
      occupied by carbohydrate, and the relevant mutants were characterized in order to
      understand the function of carbohydrate addition at those sites. Our results
      suggest that five of seven potential N-linked glycosylation sites are modified.
      In addition, mutation of asparagine 24 results in a loss of approximately 90% of
      receptor activity. This mutant is expressed at levels comparable to the wild-type
      receptor, and its activity is not significantly different from that of wild-type
      NPR-B in terms of EC50 for CNP. Ligand binding studies on this mutant further
      show that although there is no change in affinity for ligand, approximately 90%
      of receptor binding is lost. These data suggest that many of the mutant receptors
      are simply not properly folded. Our results indicate that glycosylation of
      asparagine 24 of NPR-B receptors may be critical for the formation of a competent
      ligand binding domain.

PMID- 9278253
TI  - Moderately controlled transport of ascorbate into aortic endothelial cells
      against slowdown of the cell cycle, decreasing of the concentration or increasing
      of coexistent glucose as compared with dehydroascorbate.
AB  - Uptake of L-[1-(14)C]ascorbic acid (Asc) of 12.5-200 microM for 1 h into bovine
      aortic endothelial BAE-2 cells grown to confluence was as low as 43-64% (per
      cell) of uptake into the cells grown to nearly one-fourth confluence. [14C]Asc
      undergoing transmembrane uptake was concentrated and accumulated in the cell less
      efficiently ([Asc]in/ex = 8-13) at confluence than at subconfluence ([Asc]in/ex =
      15-24). The declined Asc uptake at confluence is attributable to slowdown of the
      cell cycle, because a similar decrease in [Asc]in/ex was shown by subconfluent
      cells precultured in serum-insufficient medium, resulting in an increase in G1
      phase and concurrent decreases in S and G2 + M phase distributions as determined
      by flow cytometry. [1-(14)C]Dehydroascorbic acid (DehAsc) was taken up and
      accumulated as Asc, after metabolic reduction, without detectable DehAsc. The
      [Asc]in/ex values for DehAsc at confluence were as low as 15-69% of those at
      subconfluence in contrast to the values as retentive as 62-75% for Asc,
      suggesting the moderate control of Asc uptake against slowdown of the cell cycle.
      At either confluence or subconfluence, dose-dependence for DehAsc uptake was more
      marked than for Asc uptake as shown by an uphill slope in a curve of doses versus
      [Asc]in/ex for DehAsc in contrast to a downhill slope for Asc, suggesting the
      moderate control for Asc uptake against fluctuation of the dose. Increasing of
      coexistent glucose of 5 mM to 20-40 mM, plasma concentrations in diabetic
      patients, declined DehAsc uptake to 46-48%, which was less moderately controlled
      than Asc uptake retained to 59-73%. Asc uptake did not compete with DehAsc
      uptake, suggesting different transporter proteins for Asc and DehAsc. Thus, Asc
      uptake into the aortic endothelial cells is more moderately controlled against
      slowdown of the cell cycle, decreasing of the extracellular concentrations or
      increasing of coexistent glucose than DehAsc uptake, suggesting a homeostatic
      advantage of Asc over DehAsc in terms of retention of intracellular Asc contents
      within a definite range.

PMID- 9278254
TI  - Localization of an actin binding domain in smooth muscle myosin light chain
      kinase.
AB  - Phosphorylation of the regulatory light chain of myosin II by myosin light chain
      kinase is important for regulating many contractile processes. Smooth muscle
      myosin light chain kinase has been shown to be associated with both actin and
      myosin filaments in vitro and in vivo. In this report we define an actin binding
      region by using molecular deletions to generate recombinant mutant proteins that
      were analyzed by co-sedimentation with F-actin. An actin binding region
      restricted to residues 2-42 in the amino terminus of the rabbit smooth muscle
      myosin light chain kinase was identified.

PMID- 9278256
TI  - Redox modulation of the response of NADH oxidase activity of rat liver plasma
      membranes to cyclic AMP plus ATP.
AB  - NADH oxidase activity of rat liver plasma membranes was inhibited by low
      concentrations (1-100 nM) of ATP. The inhibition was amplified by addition of
      nanomolar concentrations (0.1-10) of cyclic AMP. The inhibition was complex and
      related to a marked increase in the Km for NADH at high NADH concentrations
      together with a concomitant decrease in the Vmax. In the absence of added or
      residual ATP, cyclic AMP was without effect. The response of cyclic AMP + ATP was
      inhibited by low concentrations of the selective inhibitor of cyclic AMP
      dependent protein kinase, H-89 but not by staurosporin. The Vmax but not the Km
      was modified by treating the plasma membranes with a mild oxidizing agent, N
      chlorosuccinamide, or with the reducing agent, dithiothreitol. In the presence of
      dithiothreitol, the Vmax was reduced by cyclic AMP + ATP. In contrast, in the
      presence of N-chlorosuccinamide, the Vmax was increased by cyclic AMP + ATP
      relative to cyclic AMP + ATP alone. Thus, the effect of cyclic AMP + ATP on the
      Vmax could be either an increase or a decrease depending on whether the membranes
      were oxidized or reduced. The results demonstrate regulation of NADH oxidase
      activity of rat liver plasma membranes through cyclic AMP-mediated
      phosphorylation by membrane-located protein kinase activities where the final
      response is dependent on the oxidation-reduction status of the plasma membranes.

PMID- 9278258
TI  - Inhibitory mechanism of lead on transferrin-bound iron uptake by rabbit
      reticulocytes: a fractal analysis.
AB  - Experimental data of transferrin and transferrin-bound iron uptake by rabbit
      reticulocytes in the presence or absence of extracellular lead is analyzed by
      means of a fractal model. A highly significant correlation of fractal dimension
      (Df) of intracellular transferrin or transferrin-bound iron uptake with varying
      extracellular concentrations of lead (0 approximately 25 umol/L) was observed
      (Transferrin: r = 0.897, p = 0.015; transferrin-bound iron: r = 0.947, p =
      0.004). The Df of membrane-bound transferrin (r = -0.618, p = 0.191) or
      transferrin-bound iron (r = 0.144, p = 0.786) did not appear to be markedly
      altered by lead. Further analysis shows that inhibitory degree of lead on
      intracellular iron uptake is higher than that on intracellular transferrin
      uptake. These results suggest that the inhibitory effect of lead on the iron
      uptake may occur in intracellular process rather than in membrane binding step,
      probably inhibiting translocation of iron across the endosomal membrane.

PMID- 9278257
TI  - Protein kinase C and calmodulin effects on the plasma membrane Ca2+-ATPase from
      excitable and nonexcitable cells.
AB  - We have purified Ca2+-ATPase from synaptosomal membranes (SM)1 from rat
      cerebellum by calmodulin affinity chromatography. The enzyme was identified as
      plasma membrane Ca2+-ATPase by its interaction with calmodulin and monoclonal
      antibodies produced against red blood cell (RBC) Ca2+-ATPase, and by thapsigargin
      insensitivity. The purpose of the study was to establish whether two regulators
      of the RBC Ca2+-ATPase, calmodulin and protein kinase C (PKC), affect the Ca2+
      ATPase isolated from excitable cells and whether their effects are comparable to
      those on the RBC Ca2+-ATPase. We found that calmodulin and PKC activated both
      enzymes. There were significant quantitative differences in the phosphorylation
      and activation of the SM versus RBC Ca2+-ATPase. The steady-state Ca2+-ATPase
      activity of SM Ca2+-ATPase was approximately 3 fold lower and significantly less
      stimulated by calmodulin. The initial rate of PKC catalyzed phosphorylation (in
      the presence of 12-myristate 13-acetate phorbol) was approximately two times
      slower for SM enzyme. While phosphorylation of RBC Ca2+-ATPase approached maximum
      level at around 5 min, comparable level of phosphorylation of SM Ca2+-ATPase was
      observed only after 30 min. The PKC-catalyzed phosphorylation resulted in a
      statistically significant increase in Ca2+-ATPase activity of up to 20-40%,
      higher in the SM Ca2+-ATPase. The differences may be associated with diversities
      in Ca2+-ATPase function in erythrocytes and neuronal cells and different isoforms
      composition.

PMID- 9278259
TI  - Transcription of mitochondrial and mitochondria-related nuclear genes in rabbit
      bladder following partial outlet obstruction.
AB  - Using the rabbit model, we showed that partial outlet obstruction of the urinary
      bladder causes significant changes in the status and expression of the
      mitochondrial (mt) genetic system in bladder smooth muscle immediately after
      obstruction is initiated. Here we investigate quantitatively the severity of the
      mt genetic response to partial outlet obstruction in both short- and long-term
      obstructed rabbits. Based on previous functional studies, bladders with mass < 6
      fold greater than control were considered compensated; bladders with mass > 6
      fold that of control were considered decompensated. Analyses of DNA from
      compensated rabbit bladders showed that relative mt genome copy number decreased
      to 30% of control values. Transcript analyses for these samples showed that mt
      RNA levels increased 3 fold to compensate for lower template copy number.
      Analysis of decompensated bladders demonstrated that mt genome copy number
      increased to approximately 90% of control levels; mt transcripts progressively
      decreased in these samples by as much as 30 fold. In contrast, transcription of a
      mt-related nuclear gene decreased 3-9 fold in compensated bladders but increased
      10-30 fold in decompensated bladders. Activity for the cytochrome oxidase
      complex, and for the mt enzyme citrate synthase, decreased steadily with
      increasing bladder hypertrophy. These data suggest that bladder dysfunction
      following partial outlet obstruction is mediated partly by a significant loss in
      mt and mt-related nuclear gene coordination.

PMID- 9278255
TI  - Hydrogen peroxide-induced expression of the proto-oncogenes, c-jun, c-fos and c
      myc in rabbit lens epithelial cells.
AB  - The involvement of H2O2 in cataract development has been established in both
      human patients and animal models. At the molecular level H2O2 has been observed
      to cause damage to DNA, protein and lipid. To explore the oxidative stress
      response of the lens system at the gene expression level, we have examined the
      effects of H2O2 on the mRNA change of the proto-oncogenes, c-jun, c-fos and c-myc
      in a rabbit lens cell line, N/N1003A. H2O2 treatment of the rabbit lens
      epithelial cells for 60 min induces quick up-regulation of both c-jun and c-fos
      mRNAs. The maximal induction is 38 fold for c-jun at 150 microM and 72 fold for c
      fos at 250 microM H2O2. Treatment of N/N1003A cells with 50-250 microM H2O2 for
      60 min leads to a 2-5 fold increase of the c-myc mRNA level. H2O2 also induces an
      up-regulation in transactivity of the activating protein-1 (AP-1) as shown with a
      reporter gene driven by a prolactin gene promoter with 4 copies of AP-1 binding
      sites inserted in the upstream of the promoter. Maximal induction occurs with 150
      microM H2O2. In the same system, the antioxidants, N-acetyl-cysteine (NAC) and
      pyrrolidine dithiocarbamate (PDTC) at concentrations shown to up-regulate the
      mRNAs of both c-jun and c-fos, also enhance the transactivity of AP-1. NAC and
      PDTC have different effects in modulating the induction of AP-1 activity by H2O2
      and TPA. These results reveal that oxidative stress regulates expression of
      various regulatory genes in lens systems, which likely affects cell
      proliferation, differentiation and viability and thus affect normal lens
      functions.

PMID- 9278261
TI  - Alcohol dehydrogenase-I from horse liver stimulates immunoglobulin production by
      human hybridoma and human peripheral blood lymphocytes.
AB  - Immunoglobulin production stimulating activity of alcohol dehydrogenase [EC
      1.1.1.1] was assessed. Alcohol dehydrogenase-I (ADH-I) derived from horse liver
      stimulated IgM production by human-human hybridoma, HB4C5 cells producing human
      lung cancer specific monoclonal IgM. IgM production of HB4C5 cells was enhanced
      more than 6 fold by the addition of ADH-I at 400 microg/ml under serum-free
      condition. However, yeast derived ADHs, such as ADH-II and -III were ineffective
      to accelerate immunoglobulin production of the hybridoma line. These results
      imply that the immunoglobulin production stimulating effect of ADH-I is
      irrelevant to its enzymatic function, and defined as a novel feature of ADH-I.
      This enzyme also stimulated IgM and IgG production by human peripheral blood
      lymphocytes 2.9 fold and 1.4 fold, respectively. This fact suggests that ADH-I
      stimulates immunoglobulin production not only by specific hybridoma cell line,
      but also by non-specific immunoglobulin producers.

PMID- 9278260
TI  - Effect of pyridine on the expression of cytochrome P450 isozymes in primary rat
      hepatocyte culture.
AB  - In vivo administration of pyridine has been shown to increase the activity and
      content of several forms of cytochrome P450 by transcriptional and
      posttranscriptional mechanisms. The effect of pyridine on CYP1A and CYP2E1
      isozymes was studied in a rat hepatocyte culture model. Hepatocytes were isolated
      from non-induced rats and seeded onto matrigel-coated dishes and incubated in
      William's medium E containing 10% fetal calf serum, hormones, and essential
      metals. Cultures were treated with 0, 10 or 25 mM pyridine for 1-3 days and
      microsomes were isolated to determine catalytic activity and for immunoblot
      analysis, and total RNA was isolated for mRNA determinations. CYP2E1 content,
      CYP2E 1 mRNA, and CYP2E1 catalyzed oxidation of p-nitrophenol declined during
      culture to values of 3, 30 and 19% that of initial, non-cultured controls by day
      3 of culture. Pyridine prevented this decline of CYP2E1 protein and activity such
      that 60-80% original activity remained after 3 days of culture in the presence of
      25 mM pyridine. However, pyridine did not prevent the fall in CYP2E1 mRNA levels,
      nor did pyridine increase the content or activity of CYP2E1 above initial values
      of microsomes from freshly isolated hepatocytes. Pyridine increased the content
      of CYP1A2 and the oxidation of ethoxyresorufin 2-4 fold compared to cultures
      incubated without pyridine over the 3 day culture period. CYP1A1 levels, which
      rapidly declined, were induced and maintained in the presence of pyridine.
      Pyridine increased CYP1A content and activity 2-3 fold over initial values of
      freshly isolated hepatocytes. These increases were associated with corresponding
      increases in CYP1A mRNA levels. CYP1A2, but not CYP1A1, mRNA levels increased in
      the cultures incubated in the absence of pyridine. These results indicate that
      pyridine has different effects on CYP1A and CYP2E1 in this hepatocyte culture
      model. Pyridine appears to modulate CYP2E1 levels by posttranscriptional
      mechanisms as CYP2E1 activity and content were maintained in the presence of
      pyridine under conditions in which CYP2E1 mRNA levels declined. These mechanisms
      may involve increased translational efficiency of existing CYP2E1 mRNA or
      stabilization of CYP2E1 protein against degradation. Pyridine increased CYP1A1
      and CYP1A2 content, activity and mRNA levels, either inducing CYP1A transcription
      or stabilizing CYP1A mRNA. Hepatocyte cultures may be a useful model to study the
      interaction of pyridine with P450 isozymes and their associated drug-mediated
      toxicity.

PMID- 9278262
TI  - Effect of dietary selenium, zinc and allopurinol supplements on plasma and tissue
      manganese levels in rats with thioacetamide [correction of thiocetamide]-induced
      liver cirrhosis.
AB  - The effect of thioacetamide-induced liver cirrhosis on plasma and tissue
      manganese levels and the protective role of selenium, zinc and allopurinol
      supplements was investigated in rats. Control plasma and liver manganese (Mn)
      levels were found to be (mean +/- SD): 8.4 +/- 2.4 mg/L and 5.7 +/- 1.5 mg/g wet
      weight respectively. Plasma manganese levels were significantly increased (p <
      0.001) whereas liver manganese levels were significantly reduced (p < 0.05) in
      the cirrhotic rats. Treatment with selenium, zinc and allopurinol reversed this
      trend and restored the manganese levels close to the normal values. Lung, spleen,
      and kidney manganese levels under control conditions were considerably lower than
      that of the liver tissue. However, these levels registered a significant increase
      (p < 0.05) in cirrhotic rats and this change was normalized after selenium, zinc
      and allopurinol treatment. There were no significant differences in the
      comparative efficacy of each of these protective agents. Zinc supplement
      considerably increased the plasma zinc levels and plasma Zn/Mn ratio had a good
      correlation with plasma zinc concentration. This ratio was significantly reduced
      in cirrhotic rats, but returned to the control level after zinc, selenium and
      allopurinol treatment. The results of this study indicate that the trace element,
      manganese, plays an important role in stabilizing cell structure and that this
      effect is mediated possibly by preserving the antioxidant activity of the
      tissues.

PMID- 9278263
TI  - Molecular cloning of the cDNA coding for regucalcin and its mRNA expression in
      mouse liver: the expression is stimulated by calcium administration.
AB  - The molecular cloning of the cDNA coding for a Ca2+-binding protein regucalcin
      and its mRNA expression in mouse liver were investigated. The cDNA clone encoding
      a regucalcin was isolated from a mouse liver cDNA library and sequenced. Analysis
      of the sequence of the cloned cDNA showed that the cDNA encoded the complete
      amino acid sequence of the mouse regucalcin molecule; the cDNA had an open
      reading frame of 897 bp. Mouse regucalcin was composed of 299 amino acid
      residues, and its molecular weight was estimated to be 33,406 Da. The amino acid
      sequence of mouse regucalcin had 94% homology, as compared with that of rat
      regucalcin. Northern blot analysis with the mouse liver cDNA probe revealed that
      mouse regucalcin mRNA was mainly present in the liver but only slightly in the
      kidney with a size of 1.8 kb. Hepatic regucalcin mRNA level of male mouse was
      higher than that of female mouse. A single intraperitoneal administration of
      calcium chloride (5, 15, and 30 mg Ca2+/100 g body weight) to mice induced a
      remarkable increase in regucalcin mRNA in the liver; the increase in regucalcin
      mRNA levels at 30 min after calcium administration was dose-dependent. The
      present results demonstrate that regucalcin mRNA in mice is uniquely expressed in
      the liver, and that its expression is stimulated by calcium administration.

PMID- 9278264
TI  - Compensatory up-regulation of cardiac SR Ca2+-pump by heat-shock counteracts SR
      Ca2+-channel activation by ischemia/reperfusion.
AB  - We tested the hypothesis that heat-shock protected myocardial Ca2+-cycling by
      sarcoplasmic reticulum from ischemia and reperfusion (I/R) injury. Twenty-four
      hours after increasing body temperature to 42 degrees C for 15 min, rat hearts
      were isolated, Langendorff-perfused, and subjected to 30 min ischemia then 30 min
      reperfusion. Left ventricles were homogenized and their ionized Ca2+
      concentration monitored with indo- during Ca2+-uptake in the presence and absence
      of the Ca2+-release channel (CRC) modulator ryanodine. Tissue content of heat
      shock protein 72 (HSP 72) was analyzed. Exposure to I/R resulted in a 37%
      enhancement of CRC activity but no effect on Ca2+-pumping activity, resulting in
      25% decreased net Ca2+-uptake activity. Pre-exposure to heat-shock resulted in a
      10-fold increase in HSP 72, and a 25% enhancement of maximal Ca2+-pumping
      activity which counteracted the effect of I/R on CRC and net Ca2+-uptake
      activities. This protection of SR Ca2+-cycling was associated with partial
      protection of myocardial physiological performance. Net Ca2+-uptake activity was
      correlated with the left ventricular developed pressure and its rate of change.
      We conclude that one of the mechanisms by which heat-shock protects myocardium
      from I/R injury is to upregulate SR Ca2+-pumping activity to counteract the
      enhanced SR Ca2+-release produced by I/R.

PMID- 9278265
TI  - Human fatty acid ethyl ester synthase-III gene: genomic organization, nucleotide
      sequencing and chromosomal localization.
AB  - The complete gene for human fatty acid ethyl ester Synthase-III (FAEES-III) was
      isolated from a human genomic lambda phage library for functional and structural
      determination. The gene spans approximately 3.3 kb which includes 791 base pairs
      of the 5' and 124 base pairs of the 3' flanking regions. The gene is comprised of
      seven exons and is interrupted by six introns. Several transcription regulatory
      sequences were identified in the promoter region. Primer extension experiments
      demonstrated the existence of two possible transcription initiation sites at
      nucleotide -29 and 32 position, 5' to the start of the translation. In addition
      to a TATA box at position-29 relative to the transcription initiation site and
      two Spl GGGCGG recognition sequences at nucleotide positions -42 to -37 and -50
      to -45, the promoter contains a sequence motif matching the transcription
      activating factor AP-1. We also found an A + T rich region between nucleotide 
      505 and -390 which contained twenty-two AAAAT tandem repeats. The gene for FAEES
      III was localized to human chromosome 11 by hybridizing the genomic fragment Xh01
      to Chinese hamster/human somatic cell hybrid panels. These data extend our
      knowledge of non-oxidative alcohol metabolism and permit linkage analyses between
      this pathway and alcohol-related phenotypes.

PMID- 9278266
TI  - Characterization of cold-induced heat shock protein expression in neonatal rat
      cardiomyocytes.
AB  - Cardiac surgery is usually performed under conditions of cardioplegic ischemic
      arrest. To protect the heart during the ischemic period, the myocardium is
      exposed to varying degrees of hypothermia. Although hyperthermia is known to
      induce the heat shock response, the molecular effects of hypothermia on the
      myocardium have not been investigated. We have studied the effect of hypothermia
      on the induction of heat shock proteins in primary cultures of neonatal
      cardiomyocytes. Cold stress in cardiomyocytes induced a 6 fold increase in the
      heat shock protein HSP70 as compared to control. Increased HSP70 protein levels
      correlated with induction of HSP70 mRNAs. Maximal levels of HSP70 protein
      appeared 4-6 h following recovery from cold shock, indicating the transient
      nature of the response. Induction of HSP25 mRNA was also observed in cold-shocked
      cardiomyocytes, even though increased HSP25 protein levels were not detected. Our
      results indicate that hypothermia is capable of inducing the heat shock response
      in neonatal cardiomyocytes.

PMID- 9278267
TI  - Regulation of lipoprotein metabolism by estrogen in inbred strains of mice occurs
      primarily by posttranscriptional mechanisms.
AB  - Estrogen protects against developing premature coronary artery disease. However,
      the mechanism of protective effects of estrogen still remains poorly understood.
      One mechanism by which estrogen can have protective effects appears to be through
      modulation of plasma lipoproteins. We showed that the mouse can be used as animal
      model to study estrogen-mediated synthesis and secretion of lipoproteins since,
      unlike the rat, the mouse does not up-regulate LDL receptors (Srivastava et al.
      [4]). Since inbred strains of mice differ in their genetic background and show
      differing responsiveness to dietary lipids, we examined how various inbred
      strains of mice respond to estradiol administration, and whether some mouse
      strains show responses similar to rats. 17beta-estradiol was administered to male
      mice from 15 different inbred strains, and the changes in plasma levels of
      lipids, apoB, apoAI, and apoE were examined. Total cholesterol decreased in all
      but one strain, apoAI levels decreased in all but 3 strains while apoB levels and
      apoB/apoAI ratios increased in all but 2 strains, suggesting that in contrast to
      rats, the apoB-containing lipoproteins increased relative to HDL in all strains
      of mice examined. Basal and estradiol-induced changes in total cholesterol were
      significantly correlated with changes in apoAI, but not apoB, reflecting the
      predominance of HDL over other lipoproteins in mouse plasma. The effects of
      estrogen on plasma apoE levels varied among various inbred strains of mice
      tested. Plasma apoE levels increased in seven strains treated with estrogen, and
      remained unchanged in the rest. To examine whether changes of plasma apoproteins
      are associated with the changes in the respective hepatic mRNA levels, apoAI, B
      and E mRNA were quantified by RNase protection assay. Hepatic apoE mRNA did not
      show correlation with either basal or post treatment plasma apoE levels in any of
      the strains. Similarly, most of the mouse strains did not show correlation of
      plasma apoAI and apoB levels with the corresponding hepatic mRNA levels. These
      results suggest that estrogen regulates plasma lipoprotein concentrations
      primarily by posttranscriptional mechanisms, and there were strain-related
      differences in the estrogen-mediated regulation of lipoprotein metabolism.

PMID- 9278269
TI  - Transferrin in cultured human term cytotrophoblast cells: synthesis and
      heterogeneity.
AB  - Transferrin (Tf) mRNA was recently demonstrated in rat and mouse placental
      tissue. Rat placental cells were shown to secrete transferrin. The cell type with
      which Tf mRNA was associated was not investigated. We therefore studied the
      ability of immunopurified human term cytotrophoblast cells in culture to
      synthesize Tf, by means of pulse-label experiments with 35S-methionine and report
      that these cells do synthesize Tf. Tf mRNA was demonstrated in the cell lysates
      by means of RT-PCR. Tf isolated from cytotrophoblast and syncytiotrophoblast
      cells was shown to be different from both maternal and fetal serum Tf with
      respect to the distribution of isoforms as demonstrated by means of iso-electric
      focusing. The iso-electric points were found at lower pH values (pH 5.0-5.4),
      compared to the iso-electric points of maternal and fetal serum Tf, suggesting a
      higher degree of sialylation and glycan chain complexity.

PMID- 9278268
TI  - Inhibitory effect of calcium-binding protein regucalcin on ribonucleic acid
      synthesis in isolated rat liver nuclei.
AB  - The effect of regucalcin, a Ca2+-binding protein isolated from rat liver cytosol,
      on ribonucleic acid (RNA) synthesis in the nuclei of normal rat liver and of
      regenerating rat liver was investigated. The liver weight at 1 day after partial
      hepatectomy was increased about 50% of that of sham-operated (control) rats.
      Calcium chloride (1.0-20 microM Ca2+ as final concentration) was added into the
      reaction mixture of nuclear RNA synthesis. RNA synthesis was established by
      incorporation of [3H]-uridine 5'-triphosphate (UTP) into the nuclear RNA.
      Addition of Ca2+ (5 and 10 microM) caused a significant increase of RNA synthesis
      in the nuclei from control rat liver. Such effect of Ca2+ was potentiated in the
      nuclei of regenerating liver; nuclear RNA synthesis was increased about 2 fold by
      the 1.0 and 2.5 microM Ca2+ addition. The stimulatory effect of Ca2+ was
      significantly inhibited by the presence of alpha-amanitin (10(-8) M), an
      inhibitor of RNA polymerase II. The presence of regucalcin (0.25 and 0.5 microM)
      significantly inhibited RNA synthesis in the nuclei from control rat liver and
      from regenerating rat liver. The inhibitory effect of regucalcin was remarkable
      in the presence of EGTA (0.5 mM), and it was weakened by the addition of Ca2+ (5
      microM). Such regucalcin effect was not seen in the presence of alpha-amanitin.
      The presence of anti-regucalcin IgG in the reaction mixture significantly
      increased RNA synthesis in the nuclei from control rat liver, indicating that the
      endogenous regucalcin may be involved in nuclear RNA synthesis. The present
      results demonstrate that regucalcin can inhibit nuclear RNA synthesis in rat
      liver. Regucalcin may have an inhibitory role in the regulation of liver nuclear
      RNA synthesis.

PMID- 9278270
TI  - Species differences in localization of cardiac cAMP-phosphodiesterase activity: a
      cytochemical study.
AB  - The localization of the membrane-bound cyclic 3',5'-AMP phosphodiesterase in
      cardiac tissues of both, rat and dog was studied by cytochemical method. 40
      microm thick slices from glutaraldehyde fixed heart tissue were incubated in the
      medium with cAMP as a substrate and Pb ions as a capture metal of the reaction
      product. The cAMP-PDE activity in the rat ventricle was only shown positive on
      the sarcolemma. Whereas, in canine ventricular tissue the cAMP-PDE activity in
      cardiomyocytes was shown on the sarcolemma, on the junctional sarcoplasmic
      reticulum and on subsarcolemmal cisternae. The results confirm differences in the
      localization of cAMP-PDE in dog and rat heart.

PMID- 9278271
TI  - RNA-mediated regulation of Receptor-Ck gene in human platelets.
AB  - The study addressed to understand the regulation of Receptor-'Ck' gene at the
      translational level revealed that exogenous cholesterol has the inherent capacity
      to regulate the endogenous synthesis of Receptor-'Ck' by initiating intracellular
      targeting of the Receptor-'Ck' to the mRNP pool within human platelets and this
      effect could be reversed when the platelets were incubated with cholesterol
      coupled with either dB cAMP or dB cGMP. Based upon these observations, we propose
      that Receptor-'Ck' initiated signalling, which involves second messengers like
      PA, cAMP and cGMP, may be responsible for the autoregulation of Receptor-'Ck'
      gene expression at the translational level.

PMID- 9278272
TI  - Ionizing radiation and TNF-alpha stimulate gene expression of a Thr/Tyr-protein
      phosphatase HVH1 and inhibitory factor IkappaB alpha in human squamous carcinoma
      cells.
AB  - Exposure of cells to ionizing radiation (IR) or tumor necrosis factor-alpha (TNF
      alpha) results in the stimulation of the DNA binding activities of transcription
      factors, AP-1 and NF-kappaB. HVH1/CL100, a dual specificity protein phosphatase,
      may attenuate the AP-1 response by dephosphorylating a key upstream element,
      mitogen-activated protein kinase (MAPK). The members of IkappaB family of
      proteins regulate the NF-kappaB response. We examined the effects of IR and TNF
      alpha on HVH1 and IkappaB alpha gene expression. Our data demonstrate that IR or
      TNF-alpha treatment of head and neck squamous carcinoma cells (PCI-04A) increased
      the steady-state levels of HVH1 and IkappaB alpha mRNAs; however, the induction
      patterns were different. TNF-alpha treatment led to a relatively prolonged
      stimulation of HVH1 and IkappaB alpha mRNAs lasting at least 7 h, while IR caused
      a transient stimulation of these mRNAs and the expression returned to basal
      levels within 6 h post-IR treatment. Treatment of cells with cycloheximide did
      not prevent the IR orTNF-alpha-inducible expression of HVH1 and IkappaB alpha
      genes, indicating that these responses were independent of the new protein
      synthesis. These data imply that protein phosphatase HVH1 and regulatory factor
      IkappaB alpha may play important roles in cellular response to IR and TNF-alpha.
      In addition, the kinetics of responsiveness indicates that the mechanisms of IR
      and TNF-alpha-induced signalling are distinct.

PMID- 9278273
TI  - Introduction of spacer peptides N-terminal to a cleavage recognition motif in
      recombinant fusion proteins can improve site-specific cleavage.
AB  - To improve site-specific cleavage of a methionyl porcine growth hormone [[Met1]
      pGH(1-46)-IGF-II] fusion protein by the enzyme H64A subtilisin, a series of
      flexible, unstructured spacer peptides were introduced N-terminal to the cleavage
      site. When enzymatic digestion preceded refolding of the fusion proteins, IGF-II
      could only be liberated from substrates which contained spacer peptides. Compared
      with the parent construct, the yield of IGF-II from refolded fusion proteins
      containing spacers was improved up to two-fold. Furthermore, this cleavage rate
      was improved by removing a competing protease recognition motif from the fusion
      partner. These data show that fusion partners can influence site-specific
      proteolysis of fusion proteins. Introduction of flexible spacers between the
      moieties can alleviate these interactions.

PMID- 9278274
TI  - Probing the structure of the ligand binding cavity of lipocalins by fluorescence
      spectroscopy.
AB  - The lipocalin superfamily constitutes a phylogenetically conserved group of more
      than 40 proteins that function in the binding and transport of a variety of
      physiologically important ligands. Members of this family subserve diverse
      functions as carriers of retinoids (retinol binding protein), odorants (odorant
      binding proteins), chromophores (insecticyanin, INS), pheromones (aphrodisin) and
      sterols (apolipoprotein D, apoD). Despite the pivotal importance of the ligand
      binding function of these proteins, a suitable approach for characterizing the
      molecular determinants of such binding has not been available. In studies using
      three homogeneously purified lipocalins INS, beta-lactoglobulin (BLG) and human
      apoD, we find that the fluorescence reporter BIS (1,1'-bi(4-anilino) naphthalene
      5,5'-disulfonic acid) is an ideal candidate for use in rapid kinetic experiments
      and in fluorescence resonance energy transfer (FRET). These methods require only
      small amounts of reagents and yield molecular coordinates of the ligand binding
      cavity of lipocalins in solution that are in remarkably close agreement to those
      obtained from crystallographic work with solids. Extremely fast ligand binding
      dynamics is indicated.

PMID- 9278275
TI  - High-resolution crystal structure of M-protease: phylogeny aided analysis of the
      high-alkaline adaptation mechanism.
AB  - M-protease is a subtilisin-family serine protease produced by an alkaliphilic
      Bacillus sp. strain. Optimal enzymatic activity of the protein occurs at pH 12.3.
      The crystal structure of M-protease (space group P2(1)2(1)2(1), a = 62.3, b =
      75.5, c = 47.2 A) has been refined to a crystallographic R-factor of 17.2% at 1.5
      A resolution. The alkaline adaptation mechanism of the enzyme was analyzed.
      Molecular phylogeny construction was used to determine the amino acid
      substitutions that occurred during the high-alkaline adaptation process. This
      analysis revealed a decrease in the number of negatively charged amino acids
      (aspartic acid and glutamic acid) and lysine residues and an increase in arginine
      and neutral hydrophilic amino acids (histidine, asparagine and glutamine)
      residues during the course of adaptation. These substitutions increased the
      isoelectric point of M-protease. Some of the acquired arginine residues form
      hydrogen bonds or ion pairs to combine both N- and C-terminal regions of M
      protease. The substituted residues are localized to a hemisphere of the globular
      protein molecule where positional shifts of peptide segments, relative to those
      of the less alkaliphilic subtilisin Carlsberg, are observed. The biased
      distribution and interactions caused by the substituted residues seem to be
      responsible for stabilization of the conformation in a high-alkaline condition.

PMID- 9278276
TI  - Protein sequence-structure compatibility criteria in terms of statistical
      hypothesis testing.
AB  - The assignment of query protein sequences to probable folds in a threading
      approach is based on the statistical analysis (learning) of structural properties
      of amino acids in known protein structures. We formalize the recognition problem
      in terms of mathematical statistics, namely statistical hypothesis testing. Our
      general formulation leads to various mathematical forms of a decision rule
      function for evaluation of the quality of a sequence-structure fit. Three
      criteria were derived according to a likelihood ratio approach. Two of them have
      new functional forms while the third happens to coincide with the mean force
      potential function previously derived under the additional assumption of the
      Boltzmann law. New decision rule functions employ (i) the Parzen estimator of a
      probability density and (ii) the newly introduced non-parametric statistic with
      known asymptotic distribution. We compared criteria efficiency by a 'structure
      seeks sequence' search for three highly populated template folds through a query
      library of non-homologous sequences of proteins with known 3D structure using
      residue accessibility as an environmental variable. Various criteria reflect
      different underlying statistical propositions and thus often recognize diverse
      correct sequence-structure matches. On the other hand, if an amino acid sequence
      is recognized as compatible with a template by each of three decision rules it
      appears that one can make a more reliable inference of sequence-structure
      relationship since almost all false positives obtained by the three criteria
      differ.

PMID- 9278278
TI  - Creation and characterization of a new, non-redundant fragment data bank.
AB  - The success achieved for protein structure prediction of loop regions with
      insertions and deletions by knowledge-based methods depends on the quality of the
      underlying information, i.e. a fragment data bank as complete as possible is
      needed. However, the greater the number of proteins contributing to the data base
      the more redundant information is included, which leads to structurally similar
      proposals in loop predictions and to longer times for extracting fragments. So it
      is not only necessary to increase the number of proteins for building the loop
      data base but also to cluster the resulting fragments according to their
      structural similarities in order to remove redundancy. Here, a new, non-redundant
      fragment data bank is described, which is based on all proteins in the Brookhaven
      Protein Data Bank (release 7/95) with a resolution > or = 2.0 A and which can be
      updated easily by including new information from structures to be solved in the
      future. In the clustering process presented, the resulting clusters are optimized
      in several cycles until self-consistency. In this way all redundant information
      is removed without loosing any significantly different fragments. Finally the
      resulting fragment data bank is analysed with respect to its completeness.

PMID- 9278277
TI  - Effectiveness of correlation analysis in identifying protein residues undergoing
      correlated evolution.
AB  - Various methods for detecting correlation between sites were evaluated by
      ascertaining their ability to discriminate positively correlated sites from
      background correlation at randomly evolved sites. A model for generating pairwise
      correlations of different degrees is also described. An assortment of
      physicochemical vectors and similarity and difference matrices were used to
      discriminate correlated change. There was little difference in effectiveness
      between the different matrices, but there were significant differences between
      the matrices and the physicochemical vectors. It is shown that all methods
      investigated exhibit significant inability to screen out background correlation,
      particularly in the presence of phylogenetic relatedness between the sequences.
      Methods using the matrices are unable to distinguish positively correlated from
      negatively correlated, or compensatory, replacements.

PMID- 9278279
TI  - Sequence and homology model of 3-isopropylmalate dehydrogenase from the
      psychrotrophic bacterium Vibrio sp. I5 suggest reasons for thermal instability.
AB  - The leuB gene from the psychrotrophic strain Vibrio sp. I5 has been cloned and
      sequenced. The gene codes for 3-isopropylmalate dehydrogenase, a 360-residue,
      dimeric enzyme involved in the biosynthesis of leucine. Three recently solved
      homologous isopropylmalate dehydrogenase (IPMDH) crystal structures from
      thermophilic and mesophilic organisms have been used to build a homology model
      for the psychrotrophic IPMDH and to deduce the possible structural reasons for
      its decreased thermostability. According to our model the psychrotrophic IPMDH
      contains fewer stabilizing interactions than its mesophilic and thermophilic
      counterparts. Elements that have been identified as destabilizing in the
      comparison of the psychrotrophic, mesophilic and thermophilic IPMDHs are a
      smaller number of salt-bridges, a reduction in aromatic-aromatic interactions,
      fewer proline residues and longer surface loops. In addition, there are a number
      of substitutions of otherwise strictly conserved residues that can be linked to
      thermostability.

PMID- 9278280
TI  - Prediction of transmembrane alpha-helices in prokaryotic membrane proteins: the
      dense alignment surface method.
AB  - A new, simple method for predicting transmembrane segments in integral membrane
      proteins has been developed. It is based on low-stringency dot-plots of the query
      sequence against a collection of non-homologous membrane proteins using a
      previously derived scoring matrix [Cserzo et al., 1994, J. Mol. Biol., 243, 388
      396]. This so-called dense alignment surface (DAS) method is shown to perform on
      par with earlier methods that require extra information in the form of multiple
      sequence alignments or the distribution of positively charged residues outside
      the transmembrane segments, and thus improves prediction abilities when only
      single-sequence information is available or for classes of membrane proteins that
      do not follow the 'positive inside' rule.

PMID- 9278281
TI  - Interactions underlying subunit association in cholinesterases.
AB  - Cholinesterases occur in a family of molecular forms, both as homo-oligomers of
      catalytic subunits, which can be either soluble, amphiphilic or lipid-anchored to
      the membrane; and hetero-oligomers of catalytic subunits and structural subunits.
      The structural subunits afford a method for precise localization of
      cholinesterases for specific function. A number of mutagenesis studies suggest
      that the C-terminal region of one alternatively spliced form of cholinesterase is
      involved in association of catalytic subunits into tetramers and in the
      association of these tetramers with structural subunits, however, there is
      currently no structural information about this region. In addition, none of the
      mutagenesis studies have clearly defined the residues important in these
      interactions. Here, multiple sequence alignment, structure prediction techniques
      and analysis of three-dimensional structural data are combined with a re
      examination of mutagenesis and biochemical data. Three-dimensional models for the
      C-terminal region and for soluble tetrameric cholinesterase are proposed, and a
      set of rules governing subunit association are formulated. The simple model for
      association of catalytic and structural subunits presented is consistent with
      data for all known cholinesterases from species as divergent as nematode and man.

PMID- 9278282
TI  - Construction of a new leucine dehydrogenase with preferred specificity for NADP+
      by site-directed mutagenesis of the strictly NAD+-specific enzyme.
AB  - On the basis of sequence comparison between NAD+-dependent leucine dehydrogenase
      (LeuDH) from Thermoactinomyces intermedius and NADP+-dependent dehydrogenases, a
      set of amino acid residues that are supposed to determine the coenzyme
      specificity of LeuDH were assigned. Systematic replacement of these amino acids
      by others was done with the aim to switch its natural coenzyme specificity to a
      new one preferring NADP+. Single D203A, double D203A-I204R and triple D203A-I204R
      D210R mutation enzymes were constructed. The wild-type LeuDH is inactive with
      NADP+. However, D203A single mutant exhibited dual specificity for NAD+ and NADP+
      with essentially identical k(cat)/Km values for both coenzymes, but the values
      were three orders of magnitude lower than that of the wild-type enzyme.
      Introduction of positive charge at 204 together with the removal of the negative
      charge at 203 in the double mutant D203A-I204R provided the enzyme with
      significantly high affinity for NADP+. The best k(cat)/Km value for NADP+ was
      shown for the triple mutant D203A-I204R-D210R: more than 2% of the k(cat)/Km
      value of the wild-type enzyme. Thus, we succeeded in constructing a mutant LeuDH
      with a new coenzyme specificity preferring NADP+ which is highly active (specific
      activity, 19 micromol/mg/min).

PMID- 9278283
TI  - Pyridoxamine-amino acid chimeras in semisynthetic aminotransferase mimics.
AB  - The transaminase activity of two new semisynthetic RNase-S proteins incorporating
      a pyridoxamine moiety at the active site has been evaluated. A chemically
      competent derivative of pyridoxamine phosphate was incorporated into the C
      peptide fragments of these non-covalent protein complexes in the form of an
      unnatural coenzyme-amino acid chimera, 'Pam'. The chimeric Pam residue integrates
      the heterocyclic functionality of pyridoxamine phosphate into the side chain of
      an alpha-amino acid and was introduced instead of Phe8 into the C-peptide
      sequence via standard solid phase methodology. The two semisynthetic Pam-RNase
      constructs were designed to probe whether the native ribonuclease catalytic
      machinery could be enlisted to modulate a pyridoxamine-dependent transamination
      reaction. Both RNase complexes, H1SP and S1SP, exhibited modest rate enhancements
      in the Cu(II)-assisted transamination of pyruvate to alanine under single
      turnover conditions, relative to 5'-deoxypyridoxamine and the uncomplexed C
      peptide fragments. Furthermore, multiple turnovers of substrates were achieved in
      the presence of added L-phenylalanine due to recycling of the pyridoxamine
      moiety. The modest chiral inductions observed in the catalytic production of
      alanine and the differences in reactivity between the two proteins could be
      rationalized by the participation of a general base (His12) in complex H1SP, and
      by the increased tolerance for large amino acid substrates by complex S1SP, which
      contains serine at this position. The pyridoxamine-amino acid chimera will be
      useful in the future for examining the coenzyme structure/ function relationships
      in a native-like peptidyl architecture.

PMID- 9278284
TI  - Pore functioning of outer membrane protein PhoE of Escherichia coli: mutagenesis
      of the constriction loop L3.
AB  - Each monomer of the trimeric outer membrane porin PhoE of Escherichia coli
      consists of a 16-stranded beta-barrel with short turns at the periplasmic side
      and large loops at the cell surface. One of these loops, L3, is folded inside the
      beta-barrel and forms a constriction within the channel. Therefore, it is assumed
      to play an important role in the permeability properties of this general
      diffusion pore. Several site-directed mutations were introduced in loop L3 to
      investigate its function. The loop L3 contains a short alpha-helix and, at the
      tip of the loop, a highly conserved PEFGG sequence. The alpha-helix was deleted
      and the two glycines in the PEFGG sequence were either replaced by alanines or
      deleted. A serine residue, supposed to play an indirect role in the anion
      selectivity of the pore, was removed. The mutant porins were analysed both in
      vitro and in vivo. The results suggest that flexibility of the third loop is
      important for solute passage and that this flexibility is determined by the two
      glycine residues in the PEFGG sequence. Furthermore, the alpha-helix is probably
      important for the folding of the protein. The supposed involvement of Ser115
      (Ser121A in OmpF nomenclature) in anion selectivity was confirmed.

PMID- 9278285
TI  - Topology of eukaryotic multispanning transmembrane proteins: use of LacZ fusions
      for the localization of cytoplasmic domains in COS.M6 cells.
AB  - In Escherichia coli, the topology of inner membrane proteins can be studied
      conveniently with the alkaline phosphatase/beta-galactosidase (PhoA/LacZ) gene
      fusion system. PhoA is enzymatically active only when fused to external domains,
      LacZ when fused to cytoplasmic domains. In eukaryotic cells, only time consuming
      methods exist to study the topology of membrane proteins. We have extended in the
      first systematic study the PhoA/LacZ gene fusion system originally developed for
      E.coli for use in eukaryotic COS.M6 cells. We have fused PhoA and LacZ to the
      putative external and cytoplasmic loops of rat aquaporin 2 (AQP2), for which a
      model with six transmembrane domains was proposed previously. The fusion proteins
      were expressed in E.coli and COS.M6 cells and immunoblot analyses and enzyme
      activity assays were performed to localize the protein domains in both cell
      types. The data obtained in E.coli correlated mostly with the predictions of the
      six transmembrane domain model. However, two fusions were found to exhibit both
      high PhoA and high LacZ activity, thereby complicating the construction of a
      complete AQP2 model. In COS.M6 cells, the PhoA fusions were inactive. In
      contrast, the LacZ fusions succeeded and showed an activity pattern in complete
      agreement with the predictions of the six transmembrane domain model. Therefore,
      LacZ fusions can localize cytoplasmic loops in COS.M6 cells by means of a simple
      enzymatic assay with high reliability and may be used in future studies to
      develop topological models of other eukaryotic membrane proteins in their
      authentic cell systems.

PMID- 9278286
TI  - Engineering trypsin-sensitive sites in a membrane transport protein.
AB  - This paper describes a systematic procedure for introducing protease-sensitive
      sites into bacterial integral membrane proteins. Such sites should make it
      possible to monitor the subcellular localization of individual domains of a
      topologically complex protein. Escherichia coli lac permease was used as a model.
      Site-directed mutagenesis, targeted to a particular periplasmic domain, was used
      to generate insertion derivatives containing a lysine residue in different
      sequence contexts. Individual mutants were then screened for lactose transport
      activity and efficient cleavage by trypsin. To facilitate this screen, the
      mutagenesis was carried out using a gene fusion encoding an easily detected,
      bifunctional lac permease-galactosidase hybrid. Insertions were identified in the
      fourth and sixth periplasmic domains (P4 and P6) that were efficiently cleaved in
      both the hybrid protein and in unfused lac permease. One of the P6 insertion
      mutants exhibited lactose transport specific activity near that of the wild-type
      and was shown by sequence analysis to be cleaved at the expected site in the
      inserted sequence. As part of this analysis, we determined the range of cellular
      concentrations of lac permease over which lactose uptake was linear. The activity
      showed a plateau at a relatively low concentration corresponding to approximately
      five times the wild-type level.

PMID- 9278287
TI  - Design of a solubilization pathway for recombinant polypeptides in vivo through
      processing of a bi-protein with a viral protease.
AB  - An artificial maturation pathway for increasing the solubility in vivo of
      recombinant proteins overproduced in Escherichia coli is reported, which is based
      on the proteolytic processing of viral polyproteins. The gene product of interest
      is expressed as a fusion to a heterologous moiety (i.e. the maltose binding
      protein, MalE) in order to increase the overall solubility of the hybrid. The
      hinge region between the two fusion partners contains a cleavage site for the NIa
      protein, a very specific protease from the plum pox potyvirus, as well as an
      affinity tag. After production, the soluble hybrid is cleaved in vivo by the
      protease, that is encoded by a plasmid harboured by a specialized E.coli host.
      The released protein remains soluble and can be purified from cell extracts by
      means of an affinity tag (a poly-His group) that becomes present after the
      cleavage. The solubilization and purification of XylR, a xylene-responsive
      transcriptional factor of Pseudomonas, with this method are reported.

PMID- 9278288
TI  - Mammalian cell expression of dimeric small immune proteins (SIP).
AB  - We have designed and expressed bivalent small immune proteins (SIP) based on scFv
      fragments connected through a short linker of four amino acids to the CH3 domain
      of the human immunoglobulin gamma 1 H-chain. Three different versions have been
      designed and expressed in mammalian cells. In one construct a cysteine residue
      was included in the last amino acid of the flexible 15-amino acid long linker
      connecting the V(L) and V(H) domains, thus creating a disulphide bond stabilized
      molecule. A version with a shorter (five amino acids) V(L)/V(H) linker was also
      produced and shown to be efficiently assembled and secreted. All three SIPs form
      dimers retaining their antigenic specificity in Western blotting and having a
      comparable functional affinity (avidity) as determined by ELISA.

PMID- 9278289
TI  - An automated approach for defining core atoms and domains in an ensemble of NMR
      derived protein structures.
AB  - A single NMR-derived protein structure is usually deposited as an ensemble
      containing many structures, each consistent with the restraint set used. The
      number of NMR-derived structures deposited in the Protein Data Bank (PDB) is
      increasing rapidly. In addition, many of the structures deposited in an ensemble
      exhibit variation in only some regions of the structure, often with the majority
      of the structure remaining largely invariant across the family of structures.
      Therefore it is useful to determine the set of atoms whose positions are 'well
      defined' across an ensemble (also known as the 'core' atoms). We have developed a
      computer program, NMRCORE, which automatically defines (i) the core atoms, and
      (ii) the rigid body(ies), or domain(s), in which they occur. The program uses a
      sorted list of the variances in individual dihedral angles across the ensemble to
      define the core, followed by the automatic clustering of the variances in
      pairwise inter-atom distances across the ensemble to define the rigid body(ies)
      which comprise the core. The program is freely available via the World Wide Web
      (http://neon.chem.le.ac.uk/nmrcore/).

PMID- 9278290
TI  - Conservation of structural features reveals the existence of a large family of
      inhibitory cell surface receptors and noninhibitory/activatory counterparts.
AB  - Immunoreceptor tyrosine-based inhibition motifs (ITIMs) consist of a 6-amino acid
      stretch (ILV)xYxx(LV). ITIMs are expressed in the intracytoplasmic domain of
      transmembrane receptors, which extinguish cell activation induced by receptors
      bearing immunoreceptor tyrosine-based activation motifs. The recent
      identification of new members of the ITIM-bearing receptor family (such as the
      signal-regulatory proteins) extends the ITIM concept to the negative regulation
      of growth factor- and oncogene-induced activation in nonhemopoietic cells. In
      addition, it appears that a feature of the family of ITIM-bearing receptors is
      the existence of noninhibitory/activatory counterparts devoid of intracytoplasmic
      ITIMs and characterized by the presence of a charged amino acid residue in their
      transmembrane domain.

PMID- 9278291
TI  - Induction of thymocyte deletion by purified single peptide/major
      histocompatibility complex ligands.
AB  - We report a novel in vitro approach that allows study of the consequences of TCR
      ligation on thymocytes in the absence of thymic stromal cells. Hence, thymocytes
      were incubated either in the presence of recombinant antigenic peptide/MHC
      complexes, which represent ligands of physiologic affinities, or with anti-TCR
      mAb, a ligand of supraphysiologic affinity. Whereas TCR cross-linking with mAb
      led to thymocyte deletion, incubation with peptide/MHC ligands did not trigger
      cellular apoptosis. However, the addition of a costimulatory signal (provided by
      anti-CD28 mAb) allowed the induction of apoptosis following TCR binding to
      peptide/MHC ligands, and it increased the levels of cell death obtained through
      mAb-mediated TCR cross-linking. Requirement for accessory signals seen with TCR
      stimulation by peptide/MHC complexes argues in favor of qualitative differences
      between TCR engagement by ligands of either physiologic or supraphysiologic
      affinity.

PMID- 9278292
TI  - Protein kinase C alpha-mediated chronic signal transduction for immunosenescence.
AB  - In CD2/protein kinase C alpha (PKC alpha)-overexpressing human CD2/rabbit PKC
      alpha transgenic mice, an aging-dependent increase in PKC alpha expression and a
      decrease in proliferative responsiveness of splenic T cells were promoted. We
      found that an aging-associated accumulation of CD44(high) CD45RB(low) memory CD4+
      T cells in exchange for CD44(low) CD45RB(high) naive CD4+ T cells was promoted in
      transgenic mice. A disequilibrium between Ag-dependent generation and subsequent
      elimination of memory T cells in these mice was shown to underlie this
      phenomenon. When stimulated with Ag, the PKC alpha transgenic mice responded
      poorly regarding Ab production and produced cytokines biased for high IFN
      gamma/IL-12 and low IL-4/IL-10 levels. These results prove, for the first time, a
      causal role for chronic signal transduction through PKC alpha in aging-associated
      immunodysfunction and provide the first animal model for genetically promoted
      immunosenescence.

PMID- 9278293
TI  - Memory, but not naive, peripheral blood B lymphocytes differentiate into Ig
      secreting cells after CD40 ligation and costimulation with IL-4 and the
      differentiation factors IL-2, IL-10, and IL-3.
AB  - The ligation of CD40 on B lymphocytes by CD40 ligand, transiently expressed on
      activated Th cells, provides a key activation signal required for the germinal
      center B cell response. In vitro, human B cell activation has been investigated
      extensively by coculturing tonsillar B cells with CD32-transfected fibroblasts
      coated with anti-CD40 Abs, in the presence of cytokines (the CD40 system). When
      tonsillar IgD+ B cells are cultured in the CD40 system with IL-4, cells
      proliferate and switch to IgG, but they display a block of differentiation
      illustrated by the persistence of IgD expression on cycling B cells. In this
      study, we analyzed the responses of peripheral blood B lymphocyte fractions,
      which may contain fewer in vivo activated cells than those from tonsils. While
      the differentiation block was confirmed with peripheral naive B cells cultured in
      the CD40 system with IL-4, it was also observed with the combination of IL-2, IL
      10, and IL-3 alone or together with IL-4 (persistence of >90% IgD+ cells,
      including 24-60% IgD+, IgG+ cells, and <6% IgD+, IgA+ cells after 8 days). IgD+,
      IgG-, and IgA- (naive) B cells secreted 70-fold less Ig than IgG+, IgA+ (memory)
      B cells in response to anti-CD40 plus IL-2, IL-10, and IL-3. IgG-, IgA- B cells,
      or IgD-, IgM+, which should include IgM+ memory cells, strongly secreted IgM, but
      no IgG. In conclusion, only memory B cells secreted Ig; like memory T cells,
      their activation requirements to differentiate into effector cells seem less
      stringent than those of the naive cells.

PMID- 9278294
TI  - Perforin-dependent cytotoxic activity and lymphokine secretion by CD4+ T cells
      are regulated by CD8+ T cells.
AB  - Factors influencing the development of CD4+ T cell subpopulations with differing
      lymphokine profiles are well established. However, CD4+ cells can show both
      perforin- and Fas ligand-dependent cytotoxicity, and little is known about
      conditions favoring the development of these effector activities. We now report
      that CD8+ cells regulate the development of perforin-dependent cytotoxicity in
      CD4+ cells. CD4+ cells activated in either the presence or absence of CD8+ cells
      developed Fas ligand-dependent cytotoxic activity. However, CD4+ cells developed
      perforin-dependent cytotoxicity only in the absence of activated CD8+ cells. CD8+
      cells also inhibited the development of IL-4-secreting CD4+ cells; however, there
      was no correlation between the expression of perforin-dependent cytotoxic
      activity and the ability to secrete IL-4, and perforin-dependent cytotoxic CD4+
      cells represented only 10% of isolated clones. This suggests that the two
      characteristics are expressed in different CD4+ subsets and might be regulated by
      distinct effects of the CD8+ cells. In keeping with this, regulation of the
      lymphokine profile of CD4+ cells by CD8+ cells was consistent with mediation by
      IFN-gamma, but only when delivered at high concentrations requiring close
      proximity of the cells. In contrast, regulation of perforin-dependent cytotoxic
      activity of CD4+ cells by CD8+ cells seemed inconsistent with an IFN-gamma
      dependent mechanism, suggesting either direct cell contact or close proximity to
      allow delivery of an unidentified soluble factor. The characteristics of perforin
      dependent CD4+ CTL and their regulation by activated CD8+ cells suggest that they
      represent a previously unrecognized subpopulation that plays a defensive role
      when a CD8+ cell response is absent.

PMID- 9278295
TI  - Positive and negative selection of functional mouse CD4 cells by porcine MHC in
      pig thymus grafts.
AB  - Specific tolerance to discordant xenogeneic donors can be achieved by grafting of
      fetal pig thymic and liver tissue (FP THY/LIV) to T cell and NK cell-depleted,
      thymectomized (ATX) mice. Mouse CD4+ T cells develop in FP THY/LIV grafts, and
      demonstrate remarkably normal immune function, including host-restricted
      responses to keyhole limpet hemocyanin. We have therefore studied the role of
      host MHC class II in the development of mouse T cells in FP THY/LIV grafts by
      comparing their development in ATX MHC class II-deficient (IIKO) and wild-type (H
      2b) mice. Mouse CD4+ T cells repopulated T/NK cell-depleted, ATX IIKO mice after
      grafting with FP THY/LIV, indicating that pig MHC can positively select mouse CD4
      cells. Expression of TCR, MHC class I, Qa-2, heat-stable Ag, and CD45RB among
      double-positive and CD4 single-positive (SP) graft thymocytes in wild-type
      recipients was similar to that in normal mouse thymi, whereas CD4 SP thymocytes
      in grafts of IIKO mice showed increased Qa-2 and decreased heat-stable Ag
      expression, suggesting an increased level of maturity. Double-positive cells in
      grafts of IIKO mice also expressed higher than normal levels of Qa-2. Deletion
      within the grafts of Vbeta3+, Vbeta5.1/5.2+, and Vbeta11+ but not Vbeta6+,
      Vbeta7+, or Vbeta8.1/8.2+ mouse CD4 SP thymocytes in ATX IIKO mice demonstrated
      that swine leukocyte Ag participates in negative selection of the T cell
      repertoire. Therefore, porcine MHC mediates positive and negative selection of
      mouse thymocytes, but host class II MHC molecules also regulate thymocyte
      maturation in xenogeneic thymic grafts.

PMID- 9278296
TI  - Human autoreactive and foreign antigen-specific T cells resist apoptosis induced
      by soluble recombinant CD95 ligand.
AB  - Mature T cells are susceptible to activation-induced cell death in the periphery.
      Activation-induced cell death is thought to involve CD95/CD95 ligand interactions
      in vivo. Here we report that stimulated, CD45RO+ human T cell lines specific for
      myelin basic protein or tetanus toxoid from multiple sclerosis patients and
      healthy individuals resist apoptosis induced by soluble recombinant CD95 ligand
      in vitro. In contrast, the same CD95 ligand effectively kills Jurkat T lymphoma
      and human malignant glioma cells. The resistance of the T cell lines is not due
      to a lack of CD95 expression at the cell surface and is not overcome by
      coexposure to CD95 ligand and inhibitors of RNA or protein synthesis. The
      expression level of BCL-2 is lower in Jurkat than in Ag-specific T cells. After
      exposure to soluble CD95 ligand, Jurkat T cells, but not Ag-specific T cells,
      exhibit loss of BCL-2 and BCL-X expression whereas BAX expression is not
      affected. Surprisingly, Ag-specific T cells are rather sensitive to CD95 ligand
      expressed at the cell surface of N2A neuroblastoma cells. Accessory molecules
      expressed by the CD95 ligand-expressing effector cell are dispensable for
      apoptosis since the T cells are equally sensitive to agonistic APO-1 Ab. Further
      studies are required to determine whether resistance to soluble CD95 ligand
      mediated apoptosis is a possible escape mechanism for T cells from peripheral
      deletion that may have relevance for autoimmune disorders.

PMID- 9278298
TI  - A mechanism underlying synergy between IL-12 and IFN-gamma-inducing factor in
      enhanced production of IFN-gamma.
AB  - IL-12 and IFN-gamma-inducing factor (IGIF) have the capacity to stimulate IFN
      gamma production by T cells. Using an IL-12-responsive T cell clone, 2D6, we
      investigated how these two cytokines collaborate for IFN-gamma production. 2D6
      obtained from cultures containing rIL-12 produced IFN-gamma in response to rIGIF.
      2D6 from cultures deprived of IL-12 for 24 h produced only marginal levels of IFN
      gamma production following stimulation with either rIL-12 or rIGIF alone.
      However, simultaneous stimulation of these 2D6 cells with both cytokines resulted
      in strikingly enhanced levels of IFN-gamma production. 2D6 could also be
      maintained in the presence of rIL-2 instead of rIL-12. 2D6 lines maintained with
      rIL-12 (2D6(IL-12)) or rIL-2 (2D6(IL-2)) exhibited differential IGIF
      responsiveness: both lines responded similarly to rIL-2 or rIL-12, whereas the
      2D6(IL-12) or 2D6(IL-2) exhibited high or marginal IGIF responsiveness,
      respectively. The 2D6(IL-12) line expressed IGIF receptor (IGIFR), whereas the
      2D6(IL-2) did not. Overnight exposure of the 2D6(IL-12) to rIL-2 reduced IGIFR
      expression and conversely, exposure of the 2D6(IL-2) to rIL-12 restored IGIFR
      expression. IGIFR expression by these 2D6 lines correlated with the capacity to
      produce IFN-gamma in response to rIGIF. Purified naive T cells stimulated with
      anti-CD3 plus anti-CD28 mAb and subsequently cultured with rIL-12 were also found
      to express IGIFR and induce enhanced IFN-gamma production following IGIF
      stimulation. These results indicate that the induction of IGIFR by IL-12
      represents one of the mechanisms underlying the synergy between IL-12 and IGIF in
      IFN-gamma production.

PMID- 9278297
TI  - Amplified follicular immune complex deposition in mice lacking the Fc receptor
      gamma-chain does not alter maturation of the B cell response.
AB  - The role of Ag-Ab complexes (or immune complexes; ICs) in the regulation of the
      maturation of the B cell immune response was investigated in mice perturbed in
      the deposition and retention of such complexes. Loss of surface expression of Fc
      gammaRI and Fc gammaRIII due to targeted disruption of the common FcR gamma-chain
      gene results in dramatically increased deposition of ICs on follicular dendritic
      cells (FDCs) in germinal centers (GCs), attributed to altered clearance of
      circulating ICs. Despite these changes in the trapping of ICs by FDCs, serum Ab
      production, V gene hypermutation, isotype class switching and Ab affinity
      maturation are overtly unaltered. Thus, substantially augmenting B cell cognate
      Ag density on FDCs does not alter the outcome of the maturation of the B cell
      response. The significance of this finding in terms of the currently accepted
      model for the generation of B cell memory is discussed.

PMID- 9278299
TI  - CD4 T cell anergy in murine AIDS: costimulation via CD28 and the addition of IL
      12 are not sufficient to rescue anergic CD4 T cells.
AB  - Murine acquired immunodeficiency syndrome (MAIDS) is a fatal disease induced by a
      mixture of retroviruses known as BM5. It is characterized by splenomegaly,
      lymphadenopathy, hypergammaglobulinemia, loss of T and B cell function, and
      development of B cell lymphomas. As the disease progresses, by wk 8 of infection,
      CD4 T cell response to Ags and mitogens is severely curtailed and the CD4 T cell
      population becomes anergic. We examined responses of anergic CD4 T cells upon
      addition of a costimulatory signal (anti-CD28) and a cytokine (IL-12), which
      might help to restore the function of cells. We report that proliferation and
      cytokine production were restored in the early stages of infection by the
      strategies we tested, but not at later stages when anergy was well established.
      We also examined the effect of the same treatments on anergy of CD4 T cells from
      thymectomized, BM5-infected mice to determine whether the rescue seen was due to
      cells freshly derived from the thymus. We report that proliferation and cytokine
      production decreased in thymectomized mice even at wk 4 of infection, indicating
      that cells that are freshly derived from thymus are the ones responding to
      treatment. This study indicates that once anergy has been established in MAIDS,
      it cannot be reversed by providing costimulation via CD28 and IL-12. Anergy of
      CD4 T cells in MAIDS appears to be different from that seen in other systems,
      both in underlying cause and in the ability of the cells to revert to a normal
      state.

PMID- 9278300
TI  - The effect of the proteasome inhibitor lactacystin on the presentation of
      transporter associated with antigen processing (TAP)-dependent and TAP
      independent peptide epitopes by class I molecules.
AB  - Cells were treated with two proteolytic inhibitors, N-acetyl-leucyl-leucyl
      norleucinal and lactacystin, the latter reported to be a specific inhibitor for
      the proteasome. Both inhibitors retarded the maturation of endo-H-resistant forms
      of murine and human class I molecules from their endo-H-sensitive precursors in
      cell lines with functional TAP proteins. HLA-A2 maturation readily occurs in TAP
      deficient T2 cells, and it has been shown that the peptides associated with A2
      are derived from the leader segment of proteins in the secretory pathway. This
      maturation is inhibited by N-acetyl-leucyl-leucyl-norleucinal but not
      lactacystin, indicating that the proteasome is not required for the generation of
      HLA-A2 binding peptides in these cells. The murine class Ib molecule Qa-1b
      presents a leader peptide derived from D-end class I molecules to alloreactive
      CTL. Since this presentation is dependent on the expression of TAP proteins, we
      determined if this requirement reflects a need for the proteasome to process this
      peptide. We found that lactacystin did not inhibit the maturation of endo-H
      resistant forms of Qa-1b that are dependent on this leader peptide for its
      maturation, nor did it inhibit the expression of this peptide-Qa-1b complex in a
      functional assay. Thus, unlike conventional cytosolic peptides, leader peptides
      (regardless of whether they are dependent on TAP for their presentation) do not
      require the proteasome for processing.

PMID- 9278301
TI  - Non-MHC-linked Th2 cell development induced by soluble protein administration
      predicts susceptibility to Leishmania major infection.
AB  - Continuous administration of soluble protein Ag followed by immunization with the
      same Ag in adjuvant results in the selective development of Ag-specific CD4+ Th2
      cells in both normal and beta2-microglobulin-deficient BALB/c mice. In addition
      to chronic administration by mini-osmotic pump, single bolus i.p., but not i.v.,
      injection of protein Ag induces Th2 cell expansion. Strong Th2 cell priming
      depends on a non-MHC-linked genetic polymorphism. It is observed in all congenic
      strains on BALB background tested, BALB/c, BALB/b, and BALB/k, but not in MHC
      matched strains on disparate genetic background, B10.D2, C57BL/6, and C3H. DBA/2
      mice appear to have an intermediate phenotype, as shown by their weaker capacity
      to mount Th2 responses as compared with BALB/c mice after soluble Ag administered
      by either mini-osmotic pumps or single bolus i.p. Conversely, induction of Th1
      cell unresponsiveness by soluble protein is observed in any mouse strain tested,
      following any mode of Ag administration. These data demonstrate that non-MHC
      linked genetic polymorphism controls the priming of Th2 but not the inhibition of
      Th1 cells induced by administration of soluble protein. The pattern of Th2
      responses in these different strains is predictive of disease outcome following
      Leishmania major infection and supports the hypothesis that systemic Ag
      presentation in the absence of strong inflammatory signals may represent an
      important stimulus leading to selective Th2 cell development in susceptible mouse
      strains.

PMID- 9278302
TI  - CD94 ligation induces apoptosis in a subset of IL-2-stimulated NK cells.
AB  - CD94 (Kp43) is a member of the human C-type lectin superfamily encoding type II
      membrane glycoproteins expressed on NK cells and a subset of T cells. Ligation of
      CD94 has been shown to either potentiate or inhibit NK cell proliferation and
      cytolytic effector function. Here we show that CD94 ligation triggers apoptosis
      in IL-2-primed NK cells. Evidence for CD94-induced apoptosis includes: 1)
      chromatin condensation as measured by increased fluorescence of Hoechst dye, 2)
      induction of DNA fragmentation, and 3) characteristic morphology by transmission
      electron microscopy. IL-2 priming (at least 12 h) is required for activation
      induced NK cell death triggered by CD94. Activation-induced NK cell death
      triggered by CD94 ligation is extremely rapid (DNA fragmentation is first
      observed at 120 min). Unlike activation-induced T cell death, it is not inhibited
      by neutralizing Abs reactive with TNF-alpha or Fas ligand. Our results suggest
      that CD94 may play a role in the elimination of activated NK cells during the
      transition from the innate to the Ag-specific immune response.

PMID- 9278303
TI  - Interleukin-11 inhibits macrophage interleukin-12 production.
AB  - IL-12 is a heterodimeric cytokine produced by phagocytic and other cells with
      important physiologic and pathologic properties. Regulated IL-12 production is
      crucial for the generation of protective Th1 responses to infectious agents. In
      contrast, IL-12 excess contributes to the pathogenesis of a variety of autoimmune
      and inflammatory disorders. To further understand the processes regulating IL-12
      production, we determined whether IL-11 regulated monocyte/macrophage production
      of this cytokine moiety. IL-11 did not alter the IL-12 (p70) production of
      unstimulated THP-1 monocytic cells or human blood monocytes. It did, however,
      inhibit, in a dose-dependent fashion, the IL-12 production of IFN-gamma plus
      Staphylococcus aureus Cowan strain 1-stimulated THP-1 cells and stimulated blood
      monocytes. This inhibition of IL-12 protein production was associated with a
      proportionate decrease in IL-12 p35 and p40 mRNA accumulation. Nuclear run-on
      assays revealed comparable decreases in IL-12 p35 and p40 gene transcription. IL
      11 did not similarly regulate monocyte/macrophage production of IL-8 or
      macrophage inflammatory protein-1alpha (MIP-1alpha) and IL-6 did not similarly
      inhibit IL-12 elaboration. These studies demonstrate that IL-11 is a potent
      inhibitor of monocyte/macrophage IL-12 production and that this inhibitory effect
      is, at least in part, transcriptionally mediated. They also demonstrate that this
      inhibition is not the result of a generalized suppression of macrophage effector
      function and that the ability to inhibit monocyte/macrophage IL-12 production is
      not a generalized property of all IL-6-type cytokines.

PMID- 9278304
TI  - CD28-induced cytokine production and proliferation by thymocytes are
      differentially regulated by the p59fyn tyrosine kinase.
AB  - CD28 is a 44-kDa homodimeric receptor that is expressed on the majority of T
      cells. Engagement of the CD28 receptor by soluble anti-CD28 mAb in conjunction
      with phorbol ester (PMA) induces the production of cytokines and the
      proliferation of resting T cells via signal transduction pathways independent of
      the TCR. Evidence is provided herein that CD28 signals leading to cytokine
      production do not require the p59fyn (Fyn) tyrosine kinase, whereas CD28-mediated
      proliferation is dependent on the presence of the Fyn kinase in thymic, but not
      lymph node, cells. The defect in proliferation is not due to failure of IL-2R
      signaling, since addition of high concentrations of exogenous IL-2 can overcome
      the proliferative defect. Analysis of CD28-directed induction of the IL-2R alpha
      (CD25)-chain, which confers high affinity binding to IL-2, showed that Fyn
      deficient thymocytes, but not lymph node cells, failed to up-regulate CD25
      expression following anti-CD28 and PMA stimulation. Thus, the Fyn tyrosine kinase
      is critically required for thymic CD28-mediated CD25 expression and proliferation
      but not for CD28-mediated cytokine production.

PMID- 9278305
TI  - Impaired class II expression and antigen uptake in monocytic cells after HIV-1
      infection.
AB  - Using the human macrophage hybridoma cell line 43 and primary monocytes, we
      investigated the regulation of class II expression and intracellular Ag
      trafficking after HIV-1 infection. The HIV-1-infected human macrophage hybridoma
      cell line, 43HIV, lost class II Ag expression, as determined by
      immunofluorescence, immunoprecipitation, and Northern blot analysis, 2 wk after
      infection. Class II expression could be restored by transfection with the full
      length HLA-DR4 cDNA driven by a CMV IE promotor. However, even after
      transfection, the 43HIV cells were incapable of presenting Ag to MHC-matched Ag
      specific T cells. This defect was associated with decreased formation of class II
      Ag complexes, and similar findings were observed in primary HIV-1BaL-infected
      monocytes. We investigated Ag uptake using FITC-labeled tetanus, OVA, and keyhole
      limpet hemocyanin. There was decreased uptake of all three Ags after HIV-1
      infection at different time points after Ag pulsing in the 43HIV cells and in
      primary HIV-1BaL-infected monocytes. There was colocalization of the FITC-labeled
      Ags with early (cathepsin D) and late endosomal markers (anti-mannose-6-phosphate
      receptor), lysosomal markers (CD-63), and acidic compartment markers (3-(2,4
      dinitroanilino)-3'-amino-N-methyldipropylamine) in the uninfected cells, but the
      level of colocalized Ag was reduced in the 43HIV cells and HIV-1BaL-infected
      monocytes. Our data suggest that class II expression, formation of class II-Ag
      complexes, and Ag uptake are impaired in chronically HIV-1-infected monocytic
      cells, which may contribute to the global immunosuppression observed in AIDS.

PMID- 9278306
TI  - T cells bearing Vbeta8 are preferentially infected with exogenous mouse mammary
      tumor virus.
AB  - We previously reported that a mouse mammary tumor virus (MMTV(II-TES14)),
      encoding a superantigen specific for TCR Vbeta14, can infect lymph node (LN)
      cells of mice in an I-E-independent manner. Here we examined the kinetics of cell
      types infected with exogenous MMTV in the draining LN after s.c. injection of II
      TES milk containing MMTV(II-TES14). The infectivity was assessed in LN cells
      sorted into each cell subset by a semiquantitative analysis of MMTV provirus
      using PCR with a primer specific for MMTV(II-TES14). Only B cells in the LN were
      infected by the MMTV on day 6 after injection, but CD8+ T cells and, to a lesser
      extent, CD4+ T cells were also found to be detectably infected on day 14 after
      the injection of II-TES milk. Among the T cells we examined, Vbeta8 T cells were
      most preferentially infected with MMTV, but no Vbeta14 T cells specific for
      MMTV(II-TES14) superantigen were infected on day 14 after infection. The transfer
      of Vbeta8 T cells sorted from mice injected with II-TES milk 14 days previously
      resulted in the deletion of CD4+ Vbeta14 T cells and in the MMTV infection of
      normal B6 mice. No MMTV infection of T cells occurred in IgM knockout mice, which
      lack a mature B cell compartment. These results suggest that MMTV surviving in B
      cells is transferred to Vbeta8 T cells, which may play an important role in MMTV
      longevity.

PMID- 9278307
TI  - Fas ligand expression is restricted to nonlymphoid thymic components in situ.
AB  - The cell surface receptor Fas (Apo-1/CD95) and its ligand (FasL) are mediators of
      apoptosis that have been shown to be implicated in activation-induced death of
      mature T cells and in killing mediated by cytolytic T cells. The role of the Fas
      pathway in apoptosis associated with thymic selection events is, however,
      controversial. Although Fas and FasL are known to be expressed in the thymus, the
      nature and in vivo localization of FasL-expressing cells have not been
      determined. Using recently developed anti-FasL Abs in combination with in situ
      hybridization on tissue sections, we show in this work that FasL-expressing cells
      are present in the thymus, particularly within the medulla. FasL mRNA was
      detected readily in thymic stromal cell extracts, but not in isolated thymocytes.
      Moreover, immunohistochemical analysis of serial tissue sections stained with Abs
      against FasL in conjunction with epithelial and dendritic cell markers indicated
      that both thymic epithelial and dendritic cells express FasL in situ. The
      coexistence of FasL-expressing stromal cells and Fas-expressing thymocytes may
      have important implications for the role of the Fas pathway in apoptosis
      associated with thymic selection events.

PMID- 9278308
TI  - Antibodies against sialophorin (CD43) enhance the capacity of dendritic cells to
      cluster and activate T lymphocytes.
AB  - CD43 is a leukocyte membrane glycoprotein rich in negatively charged sialic acid
      residues that may act as an anti-adhesion molecule. In this study, we analyzed
      the expression and function of CD43 on epidermal Langerhans cells (LC) and
      dendritic cells derived from adherent peripheral blood monocytes treated with
      granulocyte-macrophage CSF and IL-4 (Mo-DC). Both freshly isolated LC (fLC) and
      Mo-DC expressed uniformly high amounts of membrane CD43, with levels unchanged in
      48-h cultured LC or in TNF-alpha-treated Mo-DC. When fLC or Mo-DC were
      transiently preincubated with anti-CD43 mAb or neuraminidase, they formed much
      larger clusters with T cells as compared with cells incubated with control mAb.
      Moreover, a significantly increased proliferation of naive allogeneic T cells in
      a primary MLR assay was induced. Anti-CD43-treated Mo-DC also presented tetanus
      toxoid to primed T cells more efficiently. Immunofluorescence and immunogold
      electron microscopy showed that following Ab cross-linking and warming to 37
      degrees C, CD43 is progressively removed from the cell surface and is
      internalized within endosomes and vacuoles. In addition, fLC and Mo-DC incubated
      with anti-CD43 mAb increased expression of HLA-DR, ICAM-1, B7-1, B7-2, CD40, and
      CD83 after 24 h, and this was partially prevented by culturing cells in the
      presence of cycloheximide. We thus postulate that membrane CD43, other than
      serving as anti-adhesion molecule, can mediate activation signals in immature DC,
      leading to augmented expression of adhesion/costimulatory molecules and Ag
      presenting function.

PMID- 9278310
TI  - Developmental pathways of dendritic cells in vivo: distinct function, phenotype,
      and localization of dendritic cell subsets in FLT3 ligand-treated mice.
AB  - We have recently shown that Flt3 ligand administration dramatically increases
      dendritic cell (DC) numbers in various mouse tissues. This has enabled the
      identification of distinct mature DC subpopulations. These have been designated:
      population C (CD11c(bright) CD11b(bright)), D (CD11c(bright) CD11b(dull)), and E
      (CD11c(bright) CD11b(negative)) This report demonstrates that the mature DC
      subsets (C, D, and E) from Flt3 ligand-treated mice differ with respect to
      phenotype, geographic localization, and function. The myeloid Ags CD11b, F4/80,
      and Ly-6C are predominantly expressed by population C, but not D or E. In
      addition, a subset of population C-type DC expresses 33D1 and CD4. In contrast,
      DC within population D and E selectively express the lymphoid-related DC markers
      CD8alpha, DEC 205, CD1d, as well as CD23, elevated levels of CD117 (c-kit), CD24
      (HSA), CD13, and CD54. Immunohistology indicates that the different DC subsets
      reside in distinct microenvironments, with populations D and E residing in the T
      cell areas of the white pulp, while DC within population C localize in the
      marginal zones. These DC subpopulations showed different capacities to
      phagocytose FITC-zymosan and to secrete IL-12 upon stimulation with
      Staphylococcus aureus cowan I strain + IFN-gamma + granulocyte-macrophage-CSF.
      Population C-type DC were more phagocytic but secreted little inducible IL-12
      while population D- and E-type DC showed poor phagocytic capacity and secreted
      considerably higher levels of IL-12. These results underscore the importance of
      viewing DC development in vivo, as an interplay between distinct lineages and a
      maturational dependence on specific microenvironmental signals.

PMID- 9278309
TI  - IL-6 triggers cell growth via the Ras-dependent mitogen-activated protein kinase
      cascade.
AB  - IL-6 mediates growth of some human multiple myeloma (MM) cells and IL-6-dependent
      cell lines. Although three IL-6 signaling pathways (STAT1, STAT3, and Ras
      dependent MAPK cascade) have been reported, cascades mediating IL-6-triggered
      growth of MM cells and cell lines are not defined. In this study, we therefore
      characterized IL-6 signaling cascades in MM cell lines, MM patient cells, and IL
      6-dependent B9 cells to determine which pathway mediates IL-6-dependent growth.
      IL-6 induced phosphorylation of JAK kinases and gp130, regardless of the
      proliferative response of MM cells to this growth factor. Accordingly, we next
      examined downstream IL-6 signaling via the STAT3, STAT1, and Ras-dependent
      mitogen-activated protein kinase (MAPK) cascades. IL-6 triggered phosphorylation
      of STAT1 and/or STAT3 in MM cells independent of their proliferative response to
      IL-6. In contrast, IL-6 induced phosphorylation of Shc and its association with
      Sos1, as well as phosphorylation of MAPK, only in MM cells and B9 cells that
      proliferated in response to IL-6. Moreover, MAPK antisense, but not sense,
      oligonucleotide inhibited IL-6-induced proliferation of these cells. These data
      suggest that STAT1 and/or STAT3 activation may occur independently of the
      proliferative response to IL-6, and that activation of the MAPK cascade is an
      important distal pathway for IL-6-mediated growth.

PMID- 9278311
TI  - Distinct mechanisms for the induction and maintenance of allograft tolerance with
      CTLA4-Fc treatment.
AB  - A murine CTLA4/Fc gamma2a heavy chain (mCTLA4-Fc) chimeric fusion molecule was
      used in B6AF1 recipients of BALB/c pancreatic islet allografts to study the
      induction and maintenance of tolerance following inhibition of the CD28-B7
      pathway for T cell activation. Donor-specific tolerance was achieved by
      administering 100 microg of mCTLA4-Fc on alternate days for 14 days (8 total
      doses) or a single 500 microg dose of mCTLA4-Fc on day 2 after transplant.
      Tolerance was mediated by long-lived peripheral lymphocytes and showed features
      of organ and alloantigen specificity. Whereas tolerance could not be established
      in allograft recipients receiving simultaneous mCTLA4-Fc and rIL-2, previously
      tolerant animals did not reject their grafts when given IL-2, suggesting that the
      induction and maintenance phases of tolerance were distinct and separate. The
      maintenance of donor-specific tolerance was an active immunologic process that
      was CD4+ T cell dependent and could be adoptively transferred to naive
      lymphocytes, but could not be explained by apoptosis or deletion of alloreactive
      T cells. Although an IL-2-sensitive mechanism such as anergy may contribute
      toward the induction of tolerance, its maintenance involves active suppression.

PMID- 9278312
TI  - Cultured NK1.1+ CD4+ T cells produce large amounts of IL-4 and IFN-gamma upon
      activation by anti-CD3 or CD1.
AB  - NK1.1+ CD4+ T cells produce more IL-4 and IFN-gamma in response to stimulation
      with anti-CD3 than conventional CD4+ T cells that have been primed to be,
      respectively, Th2 or Th1 cells. Furthermore, NK1.1+ CD4+ T cells produce IL-4
      even if cultured in the absence of IL-4, whereas conventional CD4+ T cells
      require IL-4 to develop into IL-4 producers. The IFN-gamma-producing capacity of
      NK1.1+ CD4+ T cells is enhanced by IL-12. In addition, NK1.1+ CD4+ T cells
      produce substantial amounts of IL-3, IL-5, and IL-10 upon anti-CD3 stimulation.
      NK1.1+ CD4+ T cells can be stimulated to produce IL-4 by culture with L cells
      expressing CD1 (L-CD1), but primary IL-4 production was rather slow and weak.
      Restimulation of L-CD1-activated NK1.1+ CD4+ T cells with L-CD1 gave rise to a
      much stronger and more rapid response, yielding IL-4 production comparable with
      anti-CD3 activation of cells initially primed with anti-CD3. L-CD1 stimulation of
      L-CD1-primed cells resulted in far less IFN-gamma than that elicited by anti-CD3
      from cells that had been primed with anti-CD3, but such production is
      substantially increased by adding IL-12 to the culture. The differing patterns of
      cytokine production by NK1.1+ CD4+ T cells suggest that these cells may have
      complex effects on the priming of conventional T cells and may not simply drive
      such cells to the acquisition of a Th2 phenotype.

PMID- 9278313
TI  - CD99 (MIC2) regulates the LFA-1/ICAM-1-mediated adhesion of lymphocytes, and its
      gene encodes both positive and negative regulators of cellular adhesion.
AB  - Despite the fact that integrin-mediated lymphocyte adhesion is a crucial event
      for an appropriate immune response, little is known about the mechanisms that
      control the adhesion and deadhesion processes generated by the engagement of CD99
      between various types of immune cells. Here we report that the CD99 gene encodes
      two distinct proteins with opposite functions in the LFA-1/intercellular adhesion
      molecule 1 (ICAM-1)-mediated cell adhesion process. The two forms of the CD99
      protein are produced by alternative splicing of the CD99 gene transcript. The
      major form induced homotypic adhesion of the human B lymphoblastoid cell line IM
      9, whereas the minor, truncated form inhibited the adhesion process. Activation
      of the major form of CD99 with anti-CD99 monoclonal antibodies induced rapid
      aggregation of IM-9 cells, which was blocked by the addition of mAbs to LFA-1 or
      intracellular adhesion molecule 1. Overexpression of the minor truncated form of
      CD99 markedly down-regulated the expression of LFA-1. The two forms of CD99 are
      differentially expressed in most human cells tested and are highly conserved in
      monkey. Taken together, these observations suggest that the two forms of CD99
      function in vivo in both positive and negative regulation of LFA-1-mediated
      adhesion of lymphocytes during an immune response.

PMID- 9278314
TI  - IL-7 activates alpha4beta1 integrin in murine thymocytes.
AB  - IL-7, a cytokine produced by thymic epithelium, was shown to induce adhesion of
      murine thymocytes to gelatin-coated membranes. A major binding component of
      gelatin was identified as fibronectin. IL-7-induced adhesion was observed for all
      of the major thymocyte subsets, including double-negative, double-positive, and
      single-positive cells, and specific IL-7R were verified on each subset.
      Fibronectin binding was mediated via alpha4beta1 integrin (VLA-4), which is
      expressed at high levels on thymocytes. VLA-4 surface expression was not
      increased following IL-7 treatment, but was shown to undergo rapid tyrosine
      phosphorylation on the beta1 subunit. This tyrosine phosphorylation was blocked
      by genistein, which also blocked IL-7-induced adhesion. IL-7 was detected on the
      extracellular matrix of the thymus, suggesting that it could promote matrix
      association through an integrin pathway.

PMID- 9278315
TI  - The proliferative in vivo activities of lpr double-negative T cells and the
      primary role of p59fyn in their activation and expansion.
AB  - To characterize the functional status of lpr T cells and determine whether
      activation is required for DN cell expansion, we performed in vivo labeling
      experiments in MRL-+/+, MRL-lpr, and p59fyn-/- MRL-lpr (Fyn-/-) mice. Multicolor
      FACS analysis of T cells from 8-wk-old mice receiving bromodeoxyuridine (BrdUrd)
      for 9 days showed that higher proportions of CD4+ and CD8+ lymph node cells were
      dividing (BrdUrd(high)) in lpr (15%) than in +/+ mice (3%), and the proportion of
      cycling cells was even higher in the DN (71%) and CD4+ B220+ (54%) lpr subsets.
      BrdUrd chase experiments documented that activation and division in most DN cells
      was initiated subsequent to their precursor CD8+ stage. Lymphadenopathy and other
      disease manifestations were greatly reduced in Fyn-/- lpr mice concomitant to
      decreased DN cells (from 77 to 20%). BrdUrd chase experiments showed that the
      division rate, signified by conversion of DN cells from BrdUrd(high) to
      BrdUrd(low), was severely reduced in Fyn-/- compared with conventional lpr mice,
      whereas division of all other T cell subsets (CD4+, CD8+, and CD4+ B220+) was
      equal in both types of mice. We conclude that 1) DN lpr T cells, rather than
      being end stage, retain the capacity to be activated and repeatedly divide before
      reaching an anergic or replicative senescence stage; 2) the CD3 zeta-chain
      associated Fyn kinase is important to DN T cell signal transduction; 3) DN cells,
      as functional intermediates of the CD8+ subset, are highly dependent on Fas
      participation for apoptosis; and 4) DN cells contribute to the early development
      of the serologic and histologic features of the MRL-lpr lupus disease.

PMID- 9278316
TI  - Convergence of Schiff base costimulatory signaling and TCR signaling at the level
      of mitogen-activated protein kinase ERK2.
AB  - Schiff base formation on specialized T cell surface amines provides a
      costimulatory signal to T cells through a mechanism that activates Na+ and K+
      transport, substantially enhancing TCR-dependent IL-2 production. Schiff base
      forming molecules that mimic the natural carbonyl donor potently enhance immune
      responses and provide the first mechanism-based, orally active immunopotentiatory
      agents. In the present study, costimulation by the Schiff base-forming molecule
      tucaresol was investigated at the level of mitogen-activated protein kinase
      (MAPK) in T cell lines. Both TCR-directed stimulation by anti-CD3 and Schiff base
      stimulation by tucaresol produced a distinct mobility shift in MAPK,
      characterized by direct immunoblotting of cell lysate proteins subjected to SDS
      PAGE, that corresponded with increased phosphorylation. Combined TCR-CD3 and
      tucaresol stimulation substantially enhanced and prolonged the MAPK response,
      providing a biochemical basis for the costimulatory nature of the pathway
      utilized by Schiff base signaling. The MAPK affected was identified by
      immunoprecipitation as ERK2. Both the direct effects and the TCR signal-enhancing
      effects of tucaresol on MAPK activation were also demonstrated in a functional
      MAPK assay measuring substrate phosphorylation. Borohydride reduction of
      tucaresol's Schiff base-forming carbonyl group abolished both enhancement of MAPK
      phosphorylation and IL-2 production, as did a selective inhibitor of the MAPKK,
      MEK1. Tucaresol had no effect on TCR-mediated rises in intracellular free Ca2+ or
      inositol 1,4,5-triphosphate generation, while tucaresol signaling occurred
      normally in the lck-deficient J.CaM1.6 T cell line, consistent with convergence
      of tucaresol- and TCR-induced signals downstream of early TCR-mediated events.

PMID- 9278317
TI  - CD40 ligand induction on T cell subsets by peptide-presenting B cells:
      implications for development of the primary T and B cell response.
AB  - Recent data suggest that CD40 ligand (CD40L)-CD40 interactions are essential for
      up-regulation of costimulatory activity on APC and that efficient induction of
      CD40L may be pivotal to the success of a CD4 T cell response. CD40L is regulated
      primarily by TCR signaling, but high level expression on a naive T cell appears
      to require additional interactions between T cell coreceptors and APC accessory
      molecules. The data reported here show that resting B cells presenting peptide
      Ag, in contrast to both dendritic cells and preactivated B cells, induce very
      little CD40L on naive CD4 cells, which in turn is insufficient to promote APC
      costimulatory activity. We also show, however, that previously activated effector
      T cells have enhanced responsiveness to Ag when accessory molecule help is
      limiting and consequently can express high levels of CD40L after interaction with
      resting B cells. High level CD40L expression correlated with B cell activation
      and up-regulation of costimulatory activity; however, blocking studies showed
      that CD40L was only partially responsible for these phenomena. These studies
      reinforce the notion that resting B cells may be tolerogenic for naive CD4 cells
      in part because of inefficient CD40L induction. The data also suggest that a
      successful primary T cell response will only occur if either the initial
      interaction is with a dendritic cell followed by subsequent interactions of the
      effector T cells with resting APC or if nonspecific inflammatory stimuli up
      regulate accessory molecule expression on resting APC before an encounter with
      the naive T cell.

PMID- 9278319
TI  - Expression of a bcl-2 transgene reduces proliferation and slows turnover of
      developing B lymphocytes in vivo.
AB  - B lymphocyte differentiation proceeds through a series of alternating stages of
      proliferative expansion interspersed with noncycling stationary phases during
      which cells undergo either positive selection or apoptotic cell death. The
      molecular control of cell cycle progression and that of apoptosis appear to be
      interconnected. Overexpression of Bcl-2 in lymphocytes or fibroblasts antagonizes
      apoptosis and delays their transition from the quiescent state into the cell
      cycle. We have undertaken a systematic analysis of the impact of bcl-2 transgene
      expression on cell cycle distribution and turnover rate of developing B
      lymphocytes in normal mice and in mutant animals in which B cell differentiation
      is arrested at the pro-B/pre-BI or the pre-BII stage. These experiments revealed
      that overexpression of Bcl-2 reduces proliferation and slows turnover of B cells
      at all stages of development. This demonstrates that Bcl-2 can retard transition
      of B cells between the quiescent and the cycling state regardless of the
      mitogenic stimulus and the differentiation stage. The implications of these
      results for the normal control of B lymphopoiesis and for lymphomagenesis are
      discussed.

PMID- 9278318
TI  - The Lck SH2 phosphotyrosine binding site is critical for efficient TCR-induced
      processive tyrosine phosphorylation of the zeta-chain and IL-2 production.
AB  - The lymphocyte-specific tyrosine kinase Lck is essential for TCR-mediated signal
      transduction. This is in part due to its enzymatic activity as a tyrosine kinase
      responsible for TCR-induced tyrosine phosphorylation of zeta and CD3 receptor
      subunits. In addition to its catalytic domain, the Lck protein contains SH3 and
      SH2 domains capable of associating with other signaling molecules. It has been
      proposed that phosphotyrosine binding by the Lck SH2 domain may enhance substrate
      tyrosine phosphorylation by facilitating the processive phosphorylation of
      multiple sites within the TCR complex. Alternatively or additionally, it may
      function in adapter activity for facilitating required protein-protein
      interactions. Previous experiments demonstrate that overexpression of a
      constitutively activated form of Lck (F505) in the BI-141 T cell hybridoma leads
      to the Lck kinase activity-dependent enhancement of TCR-mediated signals. Here we
      demonstrate that mutation of amino acids important for SH2 phosphotyrosine
      binding significantly compromises the ability of F505 to enhance TCR-mediated
      protein tyrosine phosphorylation and Ag-induced IL-2 production in BI-141.
      Examination of the effects of TCR-regulated phosphorylation of the Lck substrate
      zeta provides in vivo evidence for a role for the Lck SH2 domain in the
      processive phosphorylation of a multiply phosphorylated substrate.

PMID- 9278320
TI  - Functional mapping of the orientation for TCR recognition of an H2-Kb-restricted
      ovalbumin peptide suggests that the beta-chain subunit can dominate the
      determination of peptide side chain specificity.
AB  - T cells recognize a complex of antigenic peptide bound to the class I or class II
      products of the MHC. Crystallographic analysis of the interaction between MHC
      class I-bound peptide fragments and specific TCR have recently been described and
      highlight the importance of the CDR3 in determining peptide specificity. The
      results presented here show functional data for TCR recognition of the H2-Kb
      class-I restricted determinant derived from OVA (SIINFEKL) that are consistent
      with the TCR orientation defined by these crystal structures. In addition, we
      also found that the beta-chain CDR3 dominates side chain specificity for the most
      exposed regions within this peptide. The data also suggest that this orientation
      and pattern of beta-chain dominance may extend to the recognition of a second H2
      Kb-restricted peptide from the herpes simplex virus type 1 glycoprotein B
      (SSIEFARL), which shares a common alpha-chain contact with the OVA peptide. These
      results are discussed in terms of a common orientation for TCR-ligand interaction
      and the greater potential for TCR beta-chain CDR3 diversity in determining
      peptide side chain specificity.

PMID- 9278321
TI  - Analysis of polymorphism in porcine MHC class I genes: alterations in signals
      recognized by human cytotoxic lymphocytes.
AB  - Elucidation of the mechanism of the immune response against transplanted porcine
      tissue is critical for the success of xenografting in humans. Both human T cells
      and NK cells recognize MHC Ags, and human receptors may bind to MHC Ags across
      species barriers. Molecular characterization of porcine MHC class I clones from
      two MHC class I loci (P1 and P14) obtained from homozygous inbred miniature swine
      of three haplotypes (aa, cc, and dd), revealed extensive conservation between
      loci, suggesting that the genes were products of duplication from a common
      ancestral sequence. The level of homology between loci was similar to that
      between the haplotypes at each locus, suggesting that intergenic exchange had
      limited divergence of these genes. Comparison of the alleles indicated that the
      polymorphism occurred in the alpha-1 and alpha-2 domains of the class I heavy
      chain, while the alpha-3 domain was highly conserved among the six genes
      analyzed. Amino acids in the alpha-2 and alpha-3 domains responsible for the
      binding of human CD8 to MHC class I were largely conserved in the porcine genes,
      but several critical residues were altered. Comparison of sequences recognized by
      human NK cell inhibitory receptors revealed that the residues critical for
      recognition by these receptors were altered in the porcine genes; thus, the
      porcine class I molecules would be unable to inhibit lysis by human NK clones
      characterized to date. This finding provides a likely explanation for the
      susceptibility of porcine cells to cytolysis by human NK cells.

PMID- 9278322
TI  - The glycosylation of IgA produced by murine B cells is altered by Th2 cytokines.
AB  - We sought to determine whether selected cytokines, known to profoundly increase
      proliferation and/or production of Ig by B cells and their progeny, also have as
      yet unrecognized effects upon IgA glycosylation. For these studies, we selected
      CH12LX mouse B lymphoma cells, a widely used model of B cell differentiation.
      Glycosylation was assessed by detection with enzyme-lectin conjugates in an
      immunoabsorption assay and verified by profiling and sequencing of the N-linked
      oligosaccharides. Stimulation of B cells with IL-4 plus IL-5 significantly alters
      the terminal glycosylation of secreted IgA, whereas LPS has a minor effect,
      despite the fact that both stimuli are equipotent at inducing Ig class switching
      and Ig secretion. Moreover, the alteration in terminal glycosylation was more
      profound on IgA secreted from surface IgM+ than from surface IgA+ CH12LX cells.
      These results suggest that the increased production of IL-4 and IL-5 by
      peripheral blood lymphocytes from IgA nephropathy patients might result in the
      production of abnormally glycosylated IgA. In turn, this abnormally glycosylated
      IgA may promote deposition of IgA in glomeruli in this disease.

PMID- 9278323
TI  - T cell-independent response to Brucella-insulin identifies a preimmune repertoire
      for insulin.
AB  - An early or preimmune repertoire for anti-insulin B cells was examined using the
      T cell-independent (TI) response to insulin conjugated to Brucella abortus (BA
      ins). mAbs from the BA-ins response reflect a repertoire present 7 to 10 days
      before the first Ab-forming cells (AFC) are detected in primary T cell-dependent
      (TD) responses to insulin. Although 4 of 6 BA-ins mAb express IgG2 isotype,
      evidence for somatic mutation is limited. A total of 9 of 12 V regions are
      identical with known V(H) or Vkappa genes, and consensus sequences suggest two
      other V genes may be in germ-line configuration. The relative avidities (50%
      inhibition of binding) of TI anti-insulins cover a broad range and are consistent
      with a germ-line anti-insulin repertoire that is functionally diverse. The V(H)s
      of 5 mAb are from two subsets of J558 genes (205.1 and 186.3) that dominate the B
      cell pool of adult mice and are different from the V(H)s used by anti-insulin mAb
      in primary TD responses. One IgM anti-insulin (mAb 301) uses V(H)-J606 and
      Vkappa1, and this mAb binds beta cells. Other TI mAb use either Vkappa5 or
      Vkappa19.3 genes and are similar to Vkappa genes used by anti-insulin mAb from TD
      responses. The data show that mutations in germ-line genes are not required for
      measurable insulin binding by monospecific mAb from adult mice. The recurrent use
      of Vkappa genes in both early (TI response) and late (TD responses) suggest that
      these structures are important in insulin binding.

PMID- 9278325
TI  - Absence of functional relevance of human transporter associated with antigen
      processing polymorphism for peptide selection.
AB  - The polymorphic TAP (TAP1 and TAP2) genes code for a heteromeric complex that
      translocates cytosolic peptides across the membrane of the endoplasmic reticulum
      where they associate with MHC class I molecules. In the rat, extensive TAP2
      polymorphism modifies the spectrum of peptides presented by MHC class I molecules
      on the cell surface. Although polymorphism of human TAP proteins is more limited,
      it has been proposed to be associated with susceptibility to autoimmune diseases.
      To analyze the peptide selectivity and transport efficiency of human TAP alleles,
      we have generated the most frequent TAP1 and TAP2 alleles using site-directed
      mutagenesis. Alleles were cloned in the baculovirus expression system and six
      TAP1/2 allelic combinations were overexpressed in Sf9 insect cells. Microsomes
      containing TAP1/2 dimers were isolated, and peptide binding assays were performed
      using random sequence peptide libraries of variable length (7-18 mer) and a 9-mer
      polyalanine peptide substituted with various amino acids in positions 1, 2, 3, 7,
      and 9. All studied allelic combinations selected peptides with identical
      substitutions and length. Furthermore, transport assays showed similar efficiency
      and kinetics of peptide translocation by the different TAP alleles. These data
      suggest that the major human TAP alleles transport identical peptide sets and are
      therefore unlikely to contribute to predisposition to autoimmune diseases.

PMID- 9278326
TI  - Assembly and retention of CD1b heavy chains in the endoplasmic reticulum.
AB  - The endoplasmic reticulum (ER) is the site for assembly of MHC class I molecules.
      Newly synthesized class I heavy chains bind calnexin, an ER-resident molecular
      chaperone, and dissociate from calnexin following association with beta2
      microglobulin (beta2m). The class I heavy chain:beta2m complex then is stabilized
      by binding endogenous peptides transported to the ER through the TAP molecules.
      Thus, both beta2m and TAP are required for class I Ag presentation. Human CD1b is
      a beta2m-associated, non-MHC-encoded glycoprotein that functions in presentation
      of lipid Ags to T cells. Despite its structural similarities with class I, CD1b
      mediated Ag presentation is TAP independent, and CD1b traffics to endocytic
      compartments for sampling exogenous Ags. Given these distinctive features of
      CD1b, we set out to analyze its assembly. Immunofluorescence microscopic analysis
      of CD1b-transfected cells with a rabbit heteroantiserum detecting only beta2m
      free CD1b heavy chains revealed a reticular pattern characteristic of ER
      staining. Consistently, CD1b heavy chains recognized by this antiserum were
      sensitive to endoglycosidase H and associated with calnexin, indicating a
      distribution restricted to the ER. Furthermore, CD1b heavy chains were confined
      to the ER in beta2m-negative cells, whereas they exited the ER and distributed in
      post-Golgi compartments when beta2m was reconstituted in these cells. These
      results suggested that assembly of CD1b heavy chains with beta2m occurred in the
      ER and that only assembled CD1b heavy chain:beta2m complexes were able to exit
      the ER and traffic to endocytic compartments, where they encounter endocytosed
      lipid Ags.

PMID- 9278324
TI  - Molecular identification of a novel family of human Ig superfamily members that
      possess immunoreceptor tyrosine-based inhibition motifs and homology to the mouse
      gp49B1 inhibitory receptor.
AB  - The co-cross-linking of gp49B1, a member of the Ig superfamily containing
      immunoreceptor tyrosine-based inhibition motifs, with the high affinity Fc
      receptor for IgE on mouse bone marrow culture-derived mast cells inhibits IgE
      dependent exocytosis and lipid mediator generation. We now describe the cloning
      of human cDNAs homologous to the mouse gp49 family. A human monocyte cDNA library
      was probed with the mouse gp49A cDNA, which is 97% identical with mouse gp49B1,
      to obtain a homologous partial cDNA that was then used to identify and clone full
      length cDNAs from monocyte and human lung cDNA libraries. The 1.6-kbp cDNA, HM18,
      predicts a 49-kDa type 1 integral membrane protein that, like mouse gp49B1,
      contains two extracellular C2 type Ig superfamily domains and two consensus
      immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic domain. ALIGN
      analysis of the amino acid sequence of the extracellular domains showed that HM18
      belongs to a family that includes mouse gp49, the bovine Fc receptor for IgG2,
      the human myeloid Fc receptor for IgA, and the human NK cell inhibitory
      receptors. The gene encoding HM18, in common with the genes for the human Fc
      receptor for IgA and the human NK cell inhibitory receptors, was localized to
      chromosome 19q13.4. Two other closely related cDNAs, each with four C2 Ig
      superfamily domains, were characterized. Transcripts for these novel Ig
      superfamily members were identified in peripheral blood monocytes, the THP-1
      monocytic cell line, human lung, human lung mast cells, and NK cells. The data
      suggest that HM18 is a novel mononuclear cell inhibitory receptor homologous to
      mouse gp49B1.

PMID- 9278327
TI  - Cytolytic T lymphocyte recognition of the immunodominant HLA-A*0201-restricted
      Melan-A/MART-1 antigenic peptide in melanoma.
AB  - The Melan-A/MART-1 gene product is frequently recognized by tumor-specific HLA-A2
      restricted CTL. An immunodominant nonapeptide has been localized to the region
      spanning residues 27-35. However, the decapeptide including residues 26-35 (the
      nonapeptide extended NH2 terminally by one residue) appeared to be recognized as
      efficiently as the nonapeptide. In this study, we show that the optimal length
      immunodominant peptide appears to correspond to the decapeptide 26-35, as
      assessed by quantitative analyses of both 4 polyclonal and 13 monoclonal
      populations of specific CTL. Functional assays of peptide binding to HLA-A2
      indicate that the decapeptide is significantly a more efficient binder than the
      nonapeptide. Moreover, analogues of the decapeptide including substitutions at a
      secondary HLA-A2 peptide anchor further improve decapeptide binding. Finally, we
      show that the functional (9 CTL clones analyzed) and structural TCR repertoire (7
      CTL clones) of a group of specific CTL clones is rather diverse. The findings
      reported here may have important implications for future peptide-based melanoma
      vaccination trials as well as for the monitoring of specific CTL responses in
      vivo.

PMID- 9278328
TI  - Heat shock protein 65 induced by gammadelta T cells prevents apoptosis of
      macrophages and contributes to host defense in mice infected with Toxoplasma
      gondii.
AB  - We previously reported that gammadelta T cells mediate the expression of
      endogenous heat shock protein 65 (HSP65) in macrophages of mice with acquired
      resistance against infection with Toxoplasma gondii. We show here that HSP65
      contributes to protective immunity by preventing apoptosis of infected
      macrophages. Macrophages of BALB/c mice, which readily acquired resistance to T.
      gondii infection with the low virulence Beverley strain, strongly expressed
      HSP65, and only a few of these macrophages underwent apoptosis. On the other
      hand, the BALB/c mice were susceptible to the infection with the high virulence
      RH strain of T. gondii; their macrophages did not express HSP65 and did undergo
      apoptosis. Mice depleted of gammadelta T cells using a mAb specific for TCR
      gammadelta became highly susceptible to infection even with the Beverley strain.
      In these mice, HSP65 expression was markedly suppressed, and their infected
      macrophages died via apoptosis. Apoptosis was induced in cultured macrophages or
      macrophage cell lines after infection in vitro with the RH strain, whereas
      apoptosis was prevented when HSP65 was induced in these cells, before infection,
      by activation with IFN-gamma and TNF-alpha. However, apoptosis associated with
      infection by T. gondii RH strain was not prevented when HSP65 synthesis was
      inhibited by introducing an antisense oligonucleotide for this protein into the
      cells before activation with IFN-gamma plus TNF-alpha. Thus, HSP65 appears to
      contribute to immunity by preventing the apoptosis of infected macrophages, and
      the high virulence Toxoplasma appears to have mechanisms that allow these
      organisms to evade the host defense system by interfering with HSP65 expression.

PMID- 9278329
TI  - Superantigen activation of immune cells evokes epithelial (T84) transport and
      barrier abnormalities via IFN-gamma and TNF alpha: inhibition of increased
      permeability, but not diminished secretory responses by TGF-beta2.
AB  - Superantigens (SAgs) are extremely potent stimulants of T cell activity that have
      been implicated in the etiopathophysiology of inflammatory disease. Here, we
      tested the hypothesis that Staphylococcus aureus enterotoxin B (SEB), a model
      SAg, can alter epithelial transport and/or barrier functions via immune
      stimulation. Confluent monolayers of the human colonic T84 epithelial cell line,
      grown on filter supports, were cocultured with SEB +/- PBMC. Subsequently, T84
      transport (consisting of baseline short-circuit current (Isc, indicates net ion
      transport) and secretory responses to carbachol and forskolin) and barrier
      functions (consisting of transepithelial resistance and fluxes of 3H-labeled
      mannitol and 51Cr-EDTA) were examined in Ussing chambers. T84 monolayers
      cocultured with SEB-activated PBMC displayed a time- and dose-dependent decrease
      in secretory responses to carbachol and forskolin and a significant increase in
      permeability. These dramatic changes in epithelial function were not due to
      reduced epithelial viability. Neutralizing Abs to IFN-gamma partially prevented
      the transport abnormalities, and Abs to TNF-alpha inhibited the increase in
      epithelial permeability. Abs to IL-1beta and IL-6 did not modulate the SEB
      activated PBMC-induced T84 pathophysiology. Addition of TGF-beta2 to conditioned
      medium from SEB-activated PBMC partially inhibited the increase in T84
      permeability but did not affect the transport abnormalities. We conclude that
      SAgs can elicit epithelial irregularities characteristic of enteric inflammation
      and that IFN-gamma and TNF-alpha are key mediators in this coculture model of
      epithelial dysfunction. Additionally, we would highlight the role that TGF-beta2
      may play in preventing prolonged increases in epithelial permeability.

PMID- 9278330
TI  - Chimeric peptides: a new approach to enhancing the immunogenicity of peptides
      with low MHC class I affinity: application in antiviral vaccination.
AB  - Recruitment of the CTL repertoire specific for subdominant epitopes that have a
      low MHC class I-binding affinity could be the way to achieve an efficient
      protective immunity against spontaneous tumors and viruses with high mutation
      rate. However, we have reported recently that subdominant peptides of influenza A
      Puerto Rico/8/34 (flu PR8) nucleoprotein (NP) with low Db affinity are only
      partially able to protect mice against lethal influenza infection. This seems to
      be due to their inability to recruit the specific CTL repertoire, and suggests
      that subdominant peptides could be used for vaccination only if they become
      highly immunogenic. In this work, we describe an approach that allows enhancement
      of the immunogenicity of every low affinity peptide presented by the Db molecule.
      It consists in producing chimeric peptides composed by amino acids from a high Db
      affinity peptide (NP366) in positions that interact with the MHC, and amino acids
      from low Db affinity nonimmunogenic influenza NP-derived peptides (NP17, NP97,
      NP330, and NP469) in positions that are exposed to the TCR. All chimeric peptides
      tested exhibited a high Db affinity and efficiently recruited the CTL repertoire
      specific for the corresponding low Db affinity peptide. Furthermore, vaccination
      with chimeric peptides that corresponded to subdominant NP17 and NP97 peptides
      induced a very potent anti-flu PR8 protective immunity.

PMID- 9278331
TI  - Growth of P511 mastocytoma cells in BALB/c mouse brain elicits CTL response
      without tumor elimination: a new tumor model for regional central nervous system
      immunity.
AB  - We have developed a murine model to explore the tumor-specific CTL response in
      the immune-privileged central nervous system using P511 mastocytoma cells. Three
      strains with varying degrees of histocompatibility to P511 cells (CD-1,
      allogeneic; BALB/c, minor histoincompatible; DBA/2, syngeneic) received tumor
      cells (10(4)) into the putamen 7 days after cannula implantation, when the blood
      brain barrier was functionally intact. Without exception, tumor formed
      reproducibly by day 7 in all strains. Tumor rejection occurred in CD-1 but not in
      BALB/c and DBA/2 mice. Using a flank injection site, both CD-1 and BALB/c, but
      not DBA/2 mice, ultimately rejected flank tumors. Analysis of tumor-specific CTL
      in BALB/c spleens revealed that P511 administration into brain or flank elicited
      similar responses: no fully activated CTL were detectable but a significantly
      expanded population of nonkilling precursors of CTL (pCTL) were present. A P511
      cell-specific pCTL population was also identified at the brain tumor site 14 days
      post-tumor introduction, indicating that pCTL, generated in the periphery,
      traffic to the tumor site in brain. These data indicate that failure to reject
      tumor in brain is neither due to lack of afferent stimulation nor to inability of
      peripheral effectors (P511 cell-specific pCTL) to reach the tumor site. We
      hypothesize that these effector cells are prevented from developing into fully
      activated CTL by conditions within the central nervous system microenvironment
      that down-regulate CTL development.

PMID- 9278332
TI  - Adsorption to aluminum hydroxide promotes the activity of IL-12 as an adjuvant
      for antibody as well as type 1 cytokine responses to HIV-1 gp120.
AB  - A series of protocols were tested to examine the adjuvant effects of IL-12 on
      humoral and type 1 cytokine responses elicited in mice by recombinant gp120
      envelope protein from HIV-1. This Ag fails to induce detectable Ab responses when
      administered s.c. alone, but stimulates low Ab levels when combined with aluminum
      hydroxide (alum). Moreover, when i.p. injected rIL-12 was included in the
      immunization, no increase in Ab production was observed. Importantly, optimal
      gp120 Ab responses were achieved by immunizing mice s.c. with gp120 and rIL-12
      simultaneously coadsorbed to alum. These animals displayed a highly polarized,
      type 1 cytokine profile, with the emergence of anti-gp120 Ig belonging to the
      IgG2 and IgG3 isotypes. In addition, a major increase occurred in Ab of the IgG1
      subclass. The superior adjuvant activity of alum-adsorbed IL-12 compared with
      that of the free cytokine correlated with the prolonged detection of IFN-gamma in
      the sera of animals immunized using the former procedure. In related experiments,
      in vitro neutralization of IL-12 was shown to inhibit IFN-gamma production by
      spleen cells from mice immunized with gp120 plus alum, but not by splenocytes
      from mice primed in the presence of IL-12, suggesting that the latter protocol
      induces a stable type 1 phenotype. These studies demonstrate that presentation of
      IL-12 on alum enhances its immunomodulatory effects and establish a protocol for
      the use of the cytokine as an adjuvant for simultaneously promoting both humoral
      Ab and type 1 cytokine responses.

PMID- 9278333
TI  - Hydrogen peroxide-mediated transcriptional induction of macrophage colony
      stimulating factor by TGF-beta1.
AB  - TGF-beta1 and macrophages are important regulators of tissue fibrosis and
      remodeling. Here we show that TGF-beta1 induces the expression of macrophage-CSF
      (M-CSF) in vascular endothelial cells via a signaling pathway(s) involving
      hydrogen peroxide (H2O2). In a time-dependent manner, TGF-beta1 produced a 10-
      and a 6-fold increase in M-CSF mRNA and protein levels after 12 h, respectively.
      This increase in M-CSF expression was attenuated by a nitric oxide donor, S
      nitrosoglutathione (GSNO), and by a nonspecific oxidase inhibitor, diphenylene
      iodonium. Furthermore, the TGF-beta1-induced M-CSF mRNA expression was inhibited
      by catalase, but not by superoxide dismutase, suggesting that H2O2 rather than
      superoxide anion (O2.-) is the primary mediator of the effects of TGF-beta1.
      Transient transfection studies using deletional M-CSF promoter constructs
      demonstrated that TGF-beta1 produced a 13-fold induction in M-CSF promoter
      activity that was repressed by >85% with GSNO and catalase, in part through
      inhibitory effects on kappaB cis-acting elements. Electrophoretic mobility shift
      assays revealed that the activation of nuclear factor-kappaB by TGF-beta1 was
      also inhibited by GSNO and catalase, but not by superoxide dismutase. In a
      concentration-dependent manner, treatment with exogenous H2O2 produced 14- and
      4.6-fold increases in M-CSF promoter activity and mRNA expression, respectively.
      These results indicate that the generation of H2O2 and activation of NF-kappaB by
      TGF-beta1 are required for the induction of M-CSF gene transcription.

PMID- 9278334
TI  - Human monocyte binding to fibronectin enhances IFN-gamma-induced early signaling
      events.
AB  - Leukocyte integrins are fundamentally important in modulating adhesion to
      extracellular matrix components and to other cells. This integrin-mediated
      adhesion controls leukocyte arrest and extravasation during the onset of
      inflammatory responses. Moreover, integrin-ligand interactions trigger signaling
      pathways that may influence leukocyte phenotype and function at sites of
      inflammation. In the current studies, we evaluated the combinatorial effects of
      monocyte adhesion and IFN-gamma on intracellular signaling pathways. IFN-gamma
      triggers a well-defined signal transduction pathway, which although not directly
      stimulated by monocyte adherence to fibronectin or arginine-glycine-aspartate
      (RGD)-coated substrata, was enhanced significantly in these matrix-adherent
      cells. Compared with monocytes in suspension or adherent on plastic surfaces,
      monocytes adherent to fibronectin or RGD exhibited a greater than threefold
      increase in steady state levels of IFN-gamma-induced mRNA for the high affinity
      Fc gammaRI receptor. By electrophoretic mobility shift assays, this increase in
      mRNA was associated with a 5- to 10-fold increase in the STAT1-containing DNA
      binding complex that binds to Fc gammaRI promoter elements. Furthermore, the
      tyrosine phosphorylation of STAT1 and the tyrosine kinases JAK1 and JAK2 was
      enhanced significantly in RGD-adherent monocytes compared with control cells.
      These results suggest a novel mechanism by which integrin-mediated cell adhesion
      can modulate the magnitude of cytokine-induced signal transduction pathways,
      thereby amplifying cellular events leading to monocyte activation and
      inflammation.

PMID- 9278335
TI  - Regulation of tissue inhibitor of metalloproteinase-1 in fibroblasts and acute
      phase proteins in hepatocytes in vitro by mouse oncostatin M, cardiotrophin-1,
      and IL-6.
AB  - Mouse oncostatin M (mOSM) has been recently cloned; however, its full spectrum of
      biologic functions has not been defined. To assess its potential role in
      inflammation, we have tested the activity of mOSM in vitro in regulation of
      fibroblasts and hepatic cells. At concentrations of 10 and 20 ng/ml, mOSM
      stimulates tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA in NIH-3T3 mouse
      embryonic fibroblasts, rat lung fibroblasts, and rat synovial fibroblasts,
      whereas mouse cardiotrophin-1 (mCT-1) or human OSM (hOSM) did not. Similarly,
      only mOSM was able to induce transcription of chloramphenicol acetyl-transferase
      (CAT) in NIH-3T3 cells transfected with a minimal TIMP-1 promoter/CAT construct.
      Mouse OSM had strong action inducing primary rat hepatocyte cultures to produce
      acute phase proteins; however, mOSM was very weak in its ability to stimulate
      acute phase protein synthesis in rat H35 cells or human HepG2 cells, which was
      consistent with weak STAT activation in H35 cells and HepG2 cells. Binding
      studies showed that NIH-3T3 cells possessed high affinity binding sites for mOSM,
      but rat H35 cells did not. On the other hand, mCT-1 and mouse IL-6 induced strong
      STAT activation as well as marked increases in acute phase protein production by
      H35 cells. These results indicate that mOSM does not share a functional receptor
      with mCT-1 or hOSM in mouse and rat cells and that hOSM does not activate the
      putatively specific OSM receptor on mouse or rat cells. These results also
      suggest that mOSM is an important cytokine in inflammation, through modulation of
      fibroblast function as well as hepatocyte responses.

PMID- 9278336
TI  - Characterization of C3-binding proteins on mouse neutrophils and platelets.
AB  - In the mouse, MCR1 and MCR2 on B lymphocytes are encoded by alternatively spliced
      Cr2 gene transcripts. Immune adherence receptors that bind C3 are present on
      mouse platelets and unstimulated neutrophils, yet they are not MCR1 or MCR2. To
      examine C3b- and C3d-binding proteins on mouse platelets and neutrophils, we
      performed C3b and C3d affinity chromatography as well as immunoprecipitation
      studies using previously described Ab to MCR1/MCR2 (mAb clones 8C12, 7G6, and 7E9
      and polyclonal Ab BRN-1). Mouse neutrophils contained a 190-kDa membrane protein
      that specifically bound to C3b-Sepharose. Preabsorption of neutrophil proteins
      with anti-MCR1/MCR2 Ab did not affect the recovery of the 190-kDa C3b-binding
      protein by subsequent C3b affinity chromatography. Thus, this protein is
      immunologically distinct from the previously described MCR1 and MCR2 proteins. By
      virtue of its size and C3b-binding capacity, the 190-kDa protein was named C3bR
      190. C3bR-190 was also apparent on platelets, but in reduced amounts. BRN-1 anti
      MCR1/MCR2 Ab immunoprecipitated proteins of 125 and 150 kDa from surface
      radiolabeled mouse platelets, which specifically bound to C3d-Sepharose. However,
      these proteins were not identified by mAb to MCR2, thus distinguishing them from
      previously described MCR2. These proteins were named C3dR-125 and C3dR-150.
      Therefore, we have identified a 190-kDa C3b-binding protein on mouse neutrophils
      and 125- and 150-kDa C3d-binding proteins on mouse platelets. These appear to be
      distinct from the heretofore identified mouse B lymphocyte MCR1 and MCR2. The
      identity of these C3b- and C3d-binding proteins on mouse neutrophils and
      platelets awaits further study.

PMID- 9278337
TI  - Enhanced expression of inducible cyclooxygenase with age in murine macrophages.
AB  - Macrophages (Mphi) from old mice produce more PGE2 than those from young mice,
      contributing to the dysregulation of the immune and inflammatory responses with
      age. This study was conducted to determine the mechanisms of the age-associated
      increase in Mphi PGE2 production. PGE2 production is influenced by the
      availability of the substrate arachidonic acid and by activity of the enzyme
      cyclooxygenase (Cox). We demonstrate that when the substrate is not the limiting
      factor, Mphi from old mice have significantly higher LPS-stimulated Cox activity
      than young mice, indicating that the age-associated increase in PGE2 production
      is due to increased enzyme activity and not to changes in substrate level. Cox
      activity is determined by the enzyme level and requires hydroperoxide for
      activation. Of the two Cox isoforms, Cox 1 is constitutively expressed in nearly
      all cells; whereas Cox 2 is induced by a wide range of ligands. Analysis of
      accumulated and de novo synthesis of constitutive Cox 1 and inducible Cox 2
      proteins showed no age-related difference in Cox 1 protein levels, but Mphi from
      old mice had higher accumulated and newly synthesized LPS-stimulated Cox 2
      protein levels than young mice. Furthermore, Mphi from old mice had higher LPS
      stimulated levels of Cox 2 mRNA compared with those from young mice. Clearly, the
      age-associated increase in LPS-stimulated PGE2 production is due to increased Cox
      activity resulting from higher Cox 2 protein and mRNA expression. These findings
      have significant implications for age-associated immune and inflammatory
      dysregulation as well as the development of preventive and therapeutic strategies
      against them.

PMID- 9278338
TI  - Absence of IL-1 signaling and reduced inflammatory response in IL-1 type I
      receptor-deficient mice.
AB  - IL-1alpha and IL-1beta are potent inflammatory cytokines that contribute to a
      number of normal physiologic processes and to the development of a number of
      inflammatory diseases. Two IL-1R, the type I and type II receptors, have been
      identified. This work describes the derivation and characterization of mice
      deficient in expression of the type I IL-1R (IL-1RI). IL-1RI-deficient mice were
      viable and fertile, but failed to respond to IL-1 in a variety of assays,
      including IL-1-induced IL-6 and E-selectin expression and IL-1-induced fever.
      Similar to IL-1beta-deficient mice, IL-1RI-deficient mice had a reduced acute
      phase response to turpentine. In contrast, IL-1RI-deficient mice had a reduced
      delayed-type hypersensitivity response and were highly susceptible to infection
      by Listeria monocytogenes. These data demonstrate that the IL-1RI is essential
      for all IL-1-mediated signaling events examined, and that both IL-1alpha and IL
      1beta are critical to the animals' response to injury and infection. These data
      also demonstrate that IL-1 function is not required for normal development or
      homeostasis.

PMID- 9278339
TI  - Chitin particle-induced cell-mediated immunity is inhibited by soluble mannan:
      mannose receptor-mediated phagocytosis initiates IL-12 production.
AB  - Previous studies showed that mouse spleen cells produced IL-12, TNF-alpha, and
      IFN-gamma when stimulated with phagocytosable-size chitin particles (N-acetyl-D
      glucosamine polymers). To dissect the mechanisms of the cytokine production in
      this study, spleen cells from BALB/c mice were cultured with 1 to 10 microm
      chitin particles, heat-killed Corynebacterium parvum vaccine, zymosan, and mannan
      (a mannose polymer)-coated latex beads (1 microm) at 1, 10, or 100 microg/ml. We
      found that these particles induced IL-12, TNF-alpha, and IFN-gamma. However,
      these cytokines were not produced when spleen cells were cultured with soluble
      chitin, mannan, or laminarin (a polymer of beta-glucan), 1 to 10 microm beta
      glucan particles, laminarin-coated latex beads, 1 microm latex beads, 50 to 100
      microm chitin particles, or 50 to 100 microm mannan-coated beads. Soluble mannan,
      but not soluble laminarin, inhibited cytokine production following stimulation
      with 1 to 10 microm chitin particles, zymosan, or heat-killed C. parvum. In
      addition, cytochalasin D also inhibited cytokine production. The treatments with
      soluble mannan or with cytochalasin D, in sharp contrast, did not inhibit LPS
      induced IL-12/IFN-gamma production or exogenous IL-12-induced IFN-gamma
      production. Finally, spleen cells from C3H/HeJ mice also showed comparable levels
      of IL-12/TNF-alpha/IFN-gamma production when induced by 1 to 10 microm chitin
      particles. Taken together, our results indicate that mannose receptor-mediated
      phagocytosis, but not the receptor-mediated pinocytosis, is highly associated
      with the production of IFN-gamma-inducing extracellular signaling factors such as
      IL-12 and TNF-alpha. The novel mechanism of phagocytosis-dependent IL-12
      production appears to be distinct from that of LPS-induced cytokine production.

PMID- 9278340
TI  - Bridging of neutrophils to target cells by opsonized zymosan enhances the
      cytotoxicity of neutrophil-produced H2O2.
AB  - Hydrogen peroxide (H2O2) is a well-established cytotoxic agent released by
      activated neutrophils into the extracellular environment. However, a maximum of
      only 5 microM H2O2 was detected in the medium when 10(6) neutrophils/ml were
      activated with opsonized zymosan (OZ), more than 50-fold lower than the
      concentration of exogenous H2O2 required to produce equivalent killing of a cell
      line. In addition PMA-activated neutrophils were noncytotoxic, despite the
      capacity of PMA to generate two- to fourfold as much H2O2 for five times longer.
      The basis for this discrepancy was explored. NaN3 increased cytotoxicity to >90%
      only when neutrophils were activated with OZ due in part to inhibition of
      myeloperoxidase-mediated hydrolysis of H2O2, while catalase completely prevented
      cytotoxicity of OZ-activated neutrophils. These results indicate that H2O2 was
      solely responsible for the observed cytotoxicity. OZ-mediated cytotoxicity was
      prevented by intermittent agitation of the cultures or by the addition of soluble
      complement receptor type 1, suggesting that a physical association between
      neutrophils and target cells mediated by OZ was required to generate a cytotoxic
      environment. Significant numbers of neutrophil-target cell aggregates were
      observed by microscopic examination only under low hydrodynamic shear conditions.
      We conclude that the cytotoxic potency of H2O2 produced by neutrophils activated
      with OZ was due to a localized high concentration of H2O2 to which the target
      cells were exposed as a result of their labile adherence to OZ. This phenomenon
      may reflect a mechanism that neutrophils have acquired for maximizing the
      antimicrobial power of extracellular oxidants toward microbes that escape
      phagocytotosis.

PMID- 9278341
TI  - In vivo transfer of engineered macrophages into the glomerulus: endogenous TGF
      beta-mediated defense against macrophage-induced glomerular cell activation.
AB  - Communication between resident glomerular cells and infiltrating macrophages
      plays a crucial role in the pathogenesis of glomerular disease. Using matrix
      metalloproteinase-9 (MMP-9) as an indicator molecule, we examined the interaction
      between mesangial cells and macrophages. Mesangial cells cocultured with
      activated macrophages or exposed to macrophage-conditioned media produced
      abundant MMP-9. We identified the stimulator secreted by macrophages as IL-1
      because mesangial cells overexpressing IL-1 receptor antagonist protein showed a
      blunted expression of MMP-9 in response to the macrophage-conditioned medium. In
      contrast, culture supernatants of mesangial cells inhibited MMP-9 production by
      macrophages in a dose-dependent fashion. This inhibitor was identified to be TGF
      beta1, since neutralization of TGF-beta1 abrogated the inhibitory effect of the
      mesangial cell-conditioned medium. To investigate whether activated macrophages
      induce glomerular MMP-9 expression, and if so, how endogenous TGF-beta1 modulates
      the induction, stimulated reporter macrophages were transferred into normal rat
      glomeruli or glomeruli in the regeneration phase of acute anti-Thy-1
      glomerulonephritis. In the normal glomeruli, MMP-9 expression was up-regulated in
      resident cells after the transfer of activated macrophages. This induction was
      substantially repressed in the regenerating glomeruli that produced active TGF
      beta1. These results point to potential mechanisms involved in glomerular control
      of MMP-9. Based upon the in vitro evidence, TGF-beta1 was identified as an
      endogenous "defender" that attenuates certain actions of infiltrating macrophages
      in the glomerulus.

PMID- 9278342
TI  - Repeated elicitation of contact hypersensitivity induces a shift in cutaneous
      cytokine milieu from a T helper cell type 1 to a T helper cell type 2 profile.
AB  - We previously demonstrated that repeated application of 2,4,6-trinitro-1
      chlorobenzene resulted in a site-restricted shift in the time course of Ag
      specific hypersensitivity responses from a typical delayed-type to an early-type
      response. Here we demonstrated that the cutaneous microenvironment at the time of
      Ag presentation to T cells in the elicitation, but not the induction, phase of
      contact hypersensitivity is responsible for the shift. To investigate the
      differences in the cutaneous cytokine milieu between the acute and chronic phases
      of contact hypersensitivity, sequential cytokine dynamics after 2,4,6-trinitro-1
      chlorobenzene application were assessed in the acute vs chronic lesions. In the
      acute lesions, increased mRNA levels for IFN-gamma and IL-2 were rapidly detected
      at 1 h and remained elevated at 12 h, while mRNA expression for IL-4 and IL-10
      was minimally up-regulated between approximately 12 and 24 h. In chronic lesions,
      high levels of constitutive expression of IL-4 mRNA were observed and IL-10 mRNA
      was dramatically up-regulated at 1 approximately 3 h in an Ag-specific fashion,
      whereas the expression of Th1-type cytokines was markedly reduced. Increased mRNA
      levels for Th2-type cytokines in the chronic lesions was also reflected at the
      protein level. These results indicate that repeated elicitation with Ag alters
      the balance of cytokines released locally, with a shift toward Th2-dominated
      responses, which would represent the natural evolution processes directed toward
      reducing a more deleterious Th1 response.

PMID- 9278343
TI  - Induction of IL-12 and chemokines by hyaluronan requires adhesion-dependent
      priming of resident but not elicited macrophages.
AB  - Components of the extracellular matrix (ECM) can regulate leukocyte activation
      and function at inflammatory sites. Low molecular weight fragments of the ECM
      glycosaminoglycan hyaluronan (LMW-HA) that accumulate in inflammation, but not
      the ubiquitous high molecular weight form of HA (HMW-HA), have been shown to
      induce cytokine and/or chemokine production by alveolar and bone-marrow derived
      macrophages. To determine the cellular requirements for responsiveness to HA, we
      compared the effects of HMW-HA and LMW-HA on resident and thioglycollate-elicited
      murine peritoneal macrophages. We demonstrate that treatment of elicited
      macrophages with LMW-HA, but not with HMW-HA, stimulated production of the
      chemokines RANTES and macrophage inflammatory protein-1alpha and -1beta. Further,
      we demonstrate that LMW-HA induced the production of biologically active IL-12, a
      proinflammatory cytokine not previously known to be regulated by cell-matrix
      interactions. The LMW-HA-induced production of IL-12 by elicited macrophages was
      inhibited by an anti-CD44 mAb that blocks HA binding. In contrast to elicited
      macrophages, freshly explanted resident peritoneal macrophages did not respond to
      LMW-HA. However, preculture in vitro before stimulation led to adhesion-dependent
      priming for LMW-HA-induced cytokine and chemokine production by resident
      macrophages. These results provide further evidence of the potential importance
      of CD44/LMW-HA interactions in regulating the immune response at sites of
      inflammation and demonstrate that the state of differentiation of macrophages may
      determine their sensitivities to matrix components.

PMID- 9278344
TI  - Changes in cytokine secretion induced by altered peptide ligands of myelin basic
      protein peptide 85-99.
AB  - Myelin basic protein (MBP)-specific T cells were isolated directly from
      peripheral blood by stimulation either with native MBPp85-99 or altered peptide
      ligands (APLs) in which substitutions of the lysine were made at position 93, a
      TCR contact residue. We report here that the APL 93A could alter the cytokine
      profile of some autoreactive MBPp85-99 reactive T cell clones, switching them
      from a Th0 phenotype secreting high concentrations of IL-4, IL-5, and IFN-gamma
      into Th2 cells secreting significantly less IFN-gamma. However, in vitro
      stimulation with the 93A peptide, in some instances, induced T cells that
      responded better to the native MBPp85-99 peptide. Functionally, the APL 93A was
      shown to act as an antagonist for IFN-gamma secretion. Based on TCR sequencing
      and single cell cloning, this alteration in cytokine profile was determined to be
      the result of the differential activation of individual T cell clones. We discuss
      the implications of these data for the strength of signal model of T cell
      activation.

PMID- 9278345
TI  - Functional heterogeneity of HLA-A*02 subtypes revealed by presentation of a MAGE
      3-encoded peptide to cytotoxic T cell clones.
AB  - The peptide-binding and presentation characteristics of seven naturally occurring
      HLA-A2 subtypes were studied using M3(271), a peptide derived from the tumor
      specific Ag encoded by gene MAGE-3, which has been shown to be processed and
      presented by A*0201+ melanoma lines. Three independent M3(271)-specific CTL
      clones were obtained from two unrelated A*0201+ donors. B lymphoblastoid cell
      lines (BLCLs) expressing A*0201, A*0207, or A*0209 could be sensitized to lysis
      by all three clones upon incubation with the relevant peptide. Furthermore, the
      same BLCLs were able to present endogenous M3(271) in IFN-gamma release assays.
      These findings demonstrate, for the first time, the existence of a functional
      overlap between A*0207 and other A*02 subtypes. One of the CTL clones also lysed
      M3(271)-pulsed BLCLs expressing A*0204 and A*0206, while the other two clones
      recognized M3(271) only in the context of either of these two subtypes. Peptide
      pulsed BLCLs expressing A*0202 or A*0205 were not lysed, although A*0205 and,
      with lower affinity, A*0202 molecules were shown to bind peptide M3(271). These
      findings have implications for the selection of cancer patients for specific
      immunotherapy with peptide M3(271).

PMID- 9278346
TI  - Prevention by anti-LFA-1 of acute myoblast death following transplantation.
AB  - Myoblast transplantation is a potential treatment for Duchenne muscular
      dystrophy. One of the problems possibly responsible for the limited success of
      clinical trials is the rapid death of the myoblasts after transplantation. To
      investigate this problem, myoblasts expressing beta-galactosidase were injected
      in the tibialis anterior muscles of mice. Beta-galactosidase activity was reduced
      by 74.7% after 3 days. Myoblast death observed at 3 days was reduced to 57.2%
      when the hosts were irradiated. This result suggested that host cells were
      contributing to this phenomenon. Transplantation in SCID and FK506-treated mice
      did not reduce cell death, indicating that mortality was not due to an acute
      specific reaction. In contrast, administration of the anti-LFA-1 (TIB-213) mAb
      markedly reduced myoblast death at 3 days without altering leukocyte tissue
      infiltration. We postulated that neutrophils were mediating myoblast mortality by
      an LFA-1-dependent mechanism. To test this hypothesis, IL-1beta-activated
      myoblasts were loaded with 6-carboxy-2',7'-dichlorodihydrofluorescein diacetate,
      di(acetoxymethylester) (DCFH), a marker for oxidative stress. Addition of
      neutrophils and zymosan-activated serum resulted in a time-dependent DCFH
      fluorescence; this neutrophil-induced oxidation was considerably inhibited by TIB
      213. These results indicate that an effective control of the inflammatory
      reaction will be necessary for any new clinical trials of myoblast
      transplantation and suggest that neutrophil-mediated myoblast injury occurs by an
      LFA-1-dependent pathway.

PMID- 9278347
TI  - Suppression of autoimmune disease and of massive lymphadenopathy in MRL/Mp
      lpr/lpr mice lacking tyrosine kinase Fyn (p59fyn).
AB  - MRL/Mp-lpr/lpr (MRL/lpr) mice suffer from a generalized autoimmune disease that
      includes autoantibody production and glomerulonephritis and develop massive
      lymphadenopathy characterized by an expanded population of CD4- CD8- B220+ T
      cells that is derived from autoreactive T cells in the periphery. Some of us
      previously reported that these atypical T cells overexpressed a gene for tyrosine
      kinase p59fyn (Fyn). To define the role of Fyn in the renal disease and
      lymphadenopathy in MRL/lpr mice, we have generated Fyn-deficient MRL/lpr mice
      whose fyn gene is replaced by the gene for beta-galactosidase. Fyn-deficient
      MRL/lpr mice developed markedly limited disease and lived more than twice as long
      as the conventional MRL/lpr mice. In the mutant mice, the production of IgG3 anti
      DNA autoantibody was significantly (p < 0.005%) reduced, and glomerular deposits
      of IgG3 and C3 were remarkably diminished. Ag receptor-mediated proliferative
      responses of Fyn-deficient splenic T cells were markedly impaired. The mutant
      mice showed delayed accumulation of the atypical CD4- CD8- B220+ T cells that
      exhibited a significantly lower activity of ZAP-70 compared with those in the
      conventional MRL/lpr mice. These data demonstrated that Fyn is involved as a
      positive regulator in the disease of MRL/lpr mice. Fyn provides a signal for both
      the expansion of autoreactive T cells and the production of IgG3 anti-DNA
      autoantibody by B cells. Thus, manipulation of Fyn may improve systemic
      autoimmune disease in humans.

PMID- 9278369
TI  - Computed radiography angiography using storage phosphor imaging plates: eight
      year's experience.
AB  - We reviewed the indications, modalities, and quality of angiographic examinations
      performed in our department from 1987 to 1994 and compared the image
      characteristics and technical convenience of three modalities: conventional film
      screen angiography, fluorographic digital subtraction angiography (F-DSA), and
      computed radiography angiography using biplane rapid changers of storage phosphor
      imaging plates (IP-CRA). IP-CRA has practically eclipsed conventional film-screen
      angiography in our radiology department. Sixty-percent of the total 700
      examinations carried out in 1994 were performed using a combination of IP-CRA and
      fluorographic digital subtraction angiography (F-DSA). The remainder were
      performed with F-DSA alone. The post-processing functions of IP-CRA like
      subtraction and change of contrast or density were useful especially in such
      regions as pulmonary, bronchial, or external carotid arterial territories, where
      high natural contrast made image processing difficult with both F-DSA and film
      screen angiography. The spatial resolution of IP-CRA was superior to that of F
      DSA and comparable to the film-screen method. It was concluded that angiography
      using imaging plates was a useful part of the digital radiography system.

PMID- 9278370
TI  - Single vertebral compression and involvement of the posterior elements in
      tuberculous spondylitis: observation on MR imaging.
AB  - To examine the atypical presentation of tuberculous spondylitis we evaluated
      seven cases seen in our hospitals during a five-year period (1989-1994) with
      procedures including MR imaging and CT scan. Three of the seven cases showed
      collapse of the single vertebral bodies with relatively spared disk spaces.
      Posterior elements were also involved on MR imaging in three cases, but the
      involvement of adjacent disks and vertebral bodies militated against metastases.

PMID- 9278371
TI  - Carbon-13 magnetic resonance spectroscopy of glucose metabolism in SCC-VII
      tumors.
AB  - We used 13C MR spectroscopy to follow the metabolism of [1-13C]glucose in SCC-VII
      tumors of C3H/HeN mice. Six different SCC-VII tumors and six muscles of normal
      legs were used. Spectroscopy was carried out with the intraperitoneal injection
      of 100 mg of [1-13C]glucose. Six distinct resonances were detected: the alpha and
      beta anomers of the C1 of glucose, C2,3,4 of glutamate and glutamine, and the C3
      of lactate. Signals from [1-13C]glucose were first detected in the spectra of
      tumor 10 minutes after injection. Signals decreased faster in the SCC-VII tumors
      than the muscle of normal leg. The presence of 13C of glutamate/glutamine
      suggested the entry of pyruvate into the TCA cycle in SCC-VII tumor. The more
      rapid decrease of signals from [1-13C]glucose in the SCC-VII tumor may be
      attributed to the effects of blood flow volume and metabolic activity.

PMID- 9278372
TI  - Electron-beam CT angiography for thoracic aortic aneurysm and dissection:
      application of continuous volume scan and electrocardiographically triggered
      scan.
AB  - PURPOSE: To assess the diagnostic value of CT angiography of thoracic aortic
      aneurysm and dissection with electron-beam CT. MATERIALS AND METHODS: Electron
      beam CT angiography was used for the evaluation of thoracic aortic aneurysm (n =
      15), and aortic dissection (n = 15). Continuous volume scan (CVS), permitted by
      continuous X-ray exposure with table incrementation, was performed in all
      patients. An additional electrocardiographically triggered scan was obtained in
      four patients. Three-dimensional surface display and multiplanar reformations
      were obtained and compared with digital subtraction angiography. RESULTS: Motion
      artifacts and the resulting degradation of three-dimensional image quality were
      frequent in the ascending aorta of CVS images. Electrocardiographically triggered
      sections improved the image quality of the ascending aorta. In the aortic arch
      and descending aorta, excellent three-dimensional images competitive in quality
      with digital subtraction angiography were obtained in all patients. For patients
      with aortic dissection, multiplanar reformation was useful to demonstrate the
      intimal flap and entry sites. CONCLUSION: The use of electron-beam CT angiography
      is feasible for the diagnosis of thoracic aortic aneurysm and dissection.

PMID- 9278374
TI  - p53 protein expression and radiation-induced apoptosis in human tumors
      transplanted to nude mice.
AB  - Relationships between p53 protein expression and radiation-induced apoptosis in
      five human tumors transplanted to nude mice were studied immunohistochemically.
      They were irradiated with 200 kV X-rays. Six hours after 2, 5, 10, or 20 Gy
      irradiation, tumors were excised and fixed. Tumors were also examined 1-48 hours
      after 10 Gy. Immunohistochemical studies were performed for analysis of p53
      protein expression. TUNEL and electron microscopic studies were performed to
      identify apoptosis. In non-irradiated control groups, the incidence of apoptosis
      was very low in all of the five tumors. Most tumor cells of the ependymoblastoma
      were p53 protein negative, but the other four tumors were p53 positive. Following
      irradiation, most tumor cells of the ependymoblastoma became p53 positive, and
      the incidence of apoptosis increased. However, we could not find significant
      changes in the percentage of p53 positive cells in the other tumors, and
      radiation-induced apoptosis in them was low or negligible. These results suggest
      that radiation-induced apoptosis in a radiosensitive human tumor is related to
      wild-type p53 protein expression. In contrast, the p53 protein expression of the
      other four human tumors should be mutant type, and it does not lead to radiation
      induced apoptosis.

PMID- 9278373
TI  - Alterations of benzodiazepine receptor binding potential in anxiety and
      somatoform disorders measured by 123I-iomazenil SPECT.
AB  - 123I-iomazenil (IMZ), a newly developed radioligand which acts on benzodiazepine
      receptors (BZR) as a partial inverse agonist, made it possible to evaluate the
      function of central BZR by single photon emission tomography (SPECT). To examine
      the alterations of the binding potential (BP) in the anxiety state, 123I-IMZ
      SPECT was performed in five patients with anxiety and somatoform disorders, and
      five epileptic patients without anxiety symptoms served as a reference. The BP of
      BZR was determined by using a table look-up procedure based on a three
      compartment, two-parameter model in the bilateral superior frontal, inferior
      frontal, temporal, parietal, occipital, and cerebellar cortex. The mean BP of
      patients with anxiety and somatoform disorders was significantly decreased in the
      superior frontal, temporal, and parietal cortex, in comparison with that of
      epileptic patients. A significant correlation was observed between the anxiety
      levels scored on the Hamilton anxiety scale and BP in the right temporal cortex
      and left superior frontal cortex. These changes in BZR revealed by SPECT suggest
      the usefulness of 123I-IMZ SPECT to objectively evaluate anxiety levels in
      patients with anxiety symptoms.

PMID- 9278375
TI  - Adult embryonal rhabdomyosarcoma showing marked response to radiotherapy: a case
      report.
AB  - A case of embryonal rhabdomyosarcoma (RMS) arising from adult lower proximal
      extremity is described. Rhabdomyosarcoma (RMS) is most common among children, but
      adult embryonal RMS is rare. The patient was a 44-year-old man with a large tumor
      of the left extremity invading to the pelvis. The histological diagnosis was
      embryonal RMS. Radiation therapy was delivered a total dose of 50 Gy to the
      tumor. Although adult RMS, usually pleomorphic type, is considered to be
      radioresistant, the tumor showed marked response to radiotherapy and local
      control was achieved easily in this case.

PMID- 9278376
TI  - Two adult cases of primary small bowel volvulus: usefulness of computed
      tomographic diagnosis.
AB  - Small bowel volvulus is usually secondary to conditions such as malrotation,
      congenital bands, postoperative adhesions, and internal hernias. Primary small
      bowel volvulus in an adult is rare, and only 14 cases had been reported in Japan
      as of 1994. Preoperative diagnosis is difficult, because clinical examinations
      and plain films are of limited diagnostic value. In our cases, CT showed signs of
      small bowel volvulus such as a U-shaped configuration or radial distribution of
      distended and fluid-filled loops of the small bowel converging toward the point
      of torsion, tightly twisted mesentery around the point of torsion (whirl sign),
      fusiform tapering loop (triangular sign in the cross section or beak sign in the
      longitudinal section), and signs of bowel ischemia or infarct such as attached
      mesenteric fluid and blurred mesenteric folds. CT enabled us to diagnose not only
      small bowel volvulus but also bowel ischemia or infarct.

PMID- 9278377
TI  - Spontaneous bacterial peritonitis in cirrhosis: enhancement of ascites on delayed
      MR imaging.
AB  - Delayed contrast enhancement of ascites in MR imaging performed in a 61-year-old
      cirrhotic patient who developed spontaneous bacterial peritonitis is discussed.
      Delayed T1-weighted spin-echo MR images after the IV injection of gadolinium
      diethylenetriamine penta-acetic acid (Gd-DTPA) showed remarkable enhancement of
      ascites. The ascites showed marked elevation in total protein value and
      neutrophil count, establishing a diagnosis of spontaneous bacterial peritonitis.
      This case suggests the potency of delayed-enhancement MR imaging for the
      prediction of spontaneous bacterial peritonitis in cirrhotic patients.

PMID- 9278378
TI  - Malignant gastrointestinal stromal tumor of the small intestine: radiologic
      pathologic correlation.
AB  - Neoplasms of the small intestine are very rare. Gastrointestinal stromal tumors
      (GISTs) are one of the new undifferentiated stromal tumors of the
      gastrointestinal tract diagnosed by immunohistochemistry. We present a case of a
      malignant GIST arising from the small intestine and report the radiologic
      characteristics of the tumor and pathological correlation. CT showed a very
      large, enhancing mass with extensive central necrosis located on the mesenteric
      side of the jejunum. A perforation into the jejunal lumen was observed by upper
      GI series. MRI showed a very large tumor which was hypointense on T2-weighted
      images. Ultrasound revealed a mixed solid and cystic mass. Grossly, the tumor was
      solid peripherally with extensive central necrosis. Microscopically, it consisted
      of spindle and epithelioid cells. Immunohistochemically, the cells stained
      positive for CD34, which is diagnostic of GIST.

PMID- 9278379
TI  - Asymptomatic adult Wilm's tumor (nephroblastoma) incidentally detected by CT.
AB  - Wilms' tumor (nephroblastoma), the most common renal neoplasm in children, is
      rarely found in adults. A 73-year-old woman with asymptomatic adult Wilms' tumor,
      incidentally detected by CT, is reported. CT and MRI showed a small mass with
      homogeneous enhancement after the administration of contrast medium.
      Ultrasonography demonstrated a well-defined echogenic mass with a halo-like,
      peripheral hypoechoic area. Selective angiography showed no tumor vessels.
      Although renal cell carcinoma should be considered in the differential diagnosis,
      it is still difficult to distinguish from small Wilms' tumor like this case.

PMID- 9278380
TI  - Dural ectasia of the optic nerve sheath in neurofibromatosis type 1: MRI
      manifestations.
AB  - Patients with neurofibromatosis type 1 (NF-1) have an increased incidence of
      optic glioma. Although spinal dural ectasia or meningocele is well represented in
      the NF-1 literature, radiologists are not as familiar with dural ectasia of the
      optic nerve sheath as spinal dural ectasia. This is a report of a pediatric
      patient with NF-1 with dural ectasia of the optic nerve sheath. This is the
      second reported case of dural ectasia of the optic nerve sheath demonstrated by
      magnetic resonance imaging.

PMID- 9278381
TI  - Prostate rhabdomyosarcoma in a young adult: a case study.
AB  - Prostate rhabdomyosarcoma is a very rare malignancy in young adults. This case
      study presents an 18-year-old adult with prostate rhabdomyosarcoma treated with a
      combined regimen of radiotherapy and chemotherapy.

PMID- 9278382
TI  - Na+/H+ exchangers of mammalian cells.

PMID- 9278383
TI  - Phosphorylation of the PEST domain of IkappaBbeta regulates the function of NF
      kappaB/IkappaBbeta complexes.
AB  - Activation of transcription factor NF-kappaB involves the signal-dependent
      degradation of basally phosphorylated inhibitors such as IkappaBalpha and
      IkappaBbeta. The gene encoding IkappaBalpha is under NF-kappaB control, which
      provides a negative feedback loop to terminate the induced NF-kappaB response.
      However, recent studies have identified a hypophosphorylated pool of IkappaBbeta
      that shields nuclear NF-kappaB from inhibition by newly synthesized IkappaBalpha.
      In the present work, we provide three lines of evidence indicating that this
      protection mechanism is regulated by the C-terminal PEST domain of IkappaBbeta.
      First, disruption of two basal phosphoacceptors present in the IkappaBbeta PEST
      domain (Ser-313 and Ser-315) yields a mutant that forms ternary complexes with NF
      kappaB and its target DNA-binding site. Second, based on in vitro mixing
      experiments, these ternary complexes are resistant to the inhibitory action of
      IkappaBalpha. Third, mutants of IkappaBbeta that are defective for
      phosphorylation at Ser-313 and Ser-315 fail to efficiently block NF-kappaB
      directed transcription in vivo, whereas replacement of these two IkappaBbeta
      residues with a phosphoserine mimetic generates a fully functional repressor.
      Taken together, our findings suggest that the functional fate of NF-kappaB when
      bound to IkappaBbeta is critically dependent on the phosphorylation status of the
      IkappaBbeta PEST domain.

PMID- 9278384
TI  - Negative regulation of mitogen-activated protein kinase activation by integrin
      alphaIIbbeta3 in platelets.
AB  - Activation of the mitogen-activated protein (MAP) kinase pathway in nucleated
      cells is dependent on both growth factor receptors and integrins engaged in cell
      adhesion. Human platelets are an interesting model for studying cell adhesion and
      the involvement of integrin engagement on extracellular signal-regulated kinase
      (ERK) activation, independently from the nuclear-DNA signal pathway. Maximal
      phosphorylation and activity of ERK2 occurred late during thrombin-induced
      platelet aggregation (90 s and later), an alphaIIbbeta3 integrin-dependent event.
      Surprisingly, alphaIIbbeta3 inhibition by the RGDS ligand peptide, or (Fab')2
      fragments of the AP-2 monoclonal antibody, resulted in a 2-fold enhancement in
      ERK2 phosphorylation and activity. A similar 2-fold enhancement of ERK2
      activation was observed in thrombasthenic platelets which are defective in
      alphaIIbbeta3 and do not aggregate. This suggests that ERK2 activation in
      thrombin-induced platelet aggregation is dependent on thrombin rather than on
      alphaIIbbeta3 and is down-regulated by alphaIIbbeta3 engaged in ligand
      (fibrinogen) binding and/or aggregation. Finally, in the absence of stirring
      which allows fibrinogen binding to alphaIIbbeta3 but prevents aggregation, ERK2
      was again overactivated. This overactivation appears to be consecutive to
      inhibition of aggregation itself and to alphaIIbbeta3 ligand binding. We conclude
      that in platelets, alphaIIbbeta3 engaged in aggregation down-regulates thrombin
      induced ERK2 activation. To our knowledge, this is the first report of a down
      regulation of the MAP kinase pathway by integrin engagement.

PMID- 9278385
TI  - The Tat protein of HIV-1 induces tumor necrosis factor-alpha production.
      Implications for HIV-1-associated neurological diseases.
AB  - Human immunodeficiency virus (HIV) infection may cause a dementing illness. HIV
      mediated dementia is clinically and pathologically correlated with the
      infiltration of activated macrophages and elevated levels of tumor necrosis
      factor (TNF)-alpha, both of which occur in an environment of small numbers of
      infected cells. We examined the possibility that HIV protein Tat, which is
      released extracellularly from infected cells, may induce the production of TNF
      alpha. Tat induced TNF-alpha mRNA and protein production dose-dependently,
      primarily in macrophages but also in astrocytic cells. The TNF-alpha induction
      was NF-kappaB-dependent and could be eliminated by inhibiting protein kinase A or
      protein tyrosine kinase activity. In addition, Tat-induced TNF-alpha release was
      also linked to phospholipase C activation. However, Tat effects were independent
      of protein kinase C. These observations suggest that Tat may provide an important
      link between HIV and macrophage/glial cell activation and suggest new therapeutic
      approaches for HIV dementia.

PMID- 9278386
TI  - Unaltered secretion of beta-amyloid precursor protein in gelatinase A (matrix
      metalloproteinase 2)-deficient mice.
AB  - The beta-amyloid peptide, which forms extracellular cerebral deposits in
      Alzheimer's disease, is derived from a large membrane-spanning glycoprotein
      referred to as the beta-amyloid precursor protein (APP). The APP is normally
      cleaved within the beta-amyloid region by a putative proteinase (alpha-secretase)
      to generate large soluble amino-terminal derivatives of APP, and this event
      prevents the beta-amyloid peptide formation. It has been suggested that the
      gelatinase A (matrix metalloproteinase 2, a 72-kDa type IV collagenase) may act
      either as alpha-secretase or as beta-secretase. Mice devoid of gelatinase A
      generated by gene targeting develop normally, except for a subtle delay in their
      growth, thus providing a useful system to examine the role of gelatinase A in the
      cleavage and secretion of APP in vivo. We show here that APP is cleaved within
      the beta-amyloid region and secreted into the extracellular milieu of brain and
      cultured fibroblasts without gelatinase A activity. The data suggest that
      gelatinase A does not play an essential role in the generation and release of
      soluble derivatives of APP at physiological conditions.

PMID- 9278387
TI  - Functional expression and characterization of skeletal muscle dihydropyridine
      receptors in Xenopus oocytes.
AB  - Dihydropyridine receptors in vertebrate skeletal muscle serve a dual role: as
      voltage sensors for excitation-contraction coupling and as voltage-activated
      calcium channels. Although they were the first of six classes of calcium channels
      to be cloned, skeletal muscle dihydropyridine receptors remain the only ones not
      functionally expressed as calcium channels in Xenopus oocytes, leading to the
      hypothesis that an interacting component is missing. Using beta1b, an isoform
      previously found in brain, we have for the first time reconstituted skeletal
      muscle calcium channel function in Xenopus oocytes. We show that this beta
      subunit is necessary for functional expression and that the alpha2delta subunit
      significantly enhances the expressed current. The majority of the alpha1 subunit
      in skeletal muscle is a truncated form. Here we show that both the full-length
      and truncated forms produce functional calcium channels in Xenopus oocytes, but
      the truncated form gives significantly larger currents. In addition, we show that
      the beta1b transcript is expressed in rat skeletal muscle, although at a much
      lower level than the abundant beta1a isoform.

PMID- 9278388
TI  - Nerve growth factor-independent reduction in choline acetyltransferase activity
      in PC12 cells expressing mutant presenilin-1.
AB  - Mutations in the presenilin genes (PS-1 and PS-2) are linked to early onset
      familial Alzheimer's disease (AD), but the mechanisms by which these mutations
      cause the cognitive impairment characteristic of AD are unknown. Basal forebrain
      cholinergic neurons are involved in learning and memory processes, and reductions
      in choline acetyl-transferase (ChAT) activity are a characteristic feature of AD
      brain. We therefore hypothesized that presenilin mutations suppress expression of
      the cholinergic phenotype. In rat PC12 cells stably transfected with the human PS
      1 gene containing the Leu --> Val mutation at codon 286 (L286V), we observed a
      drastic reduction (>90%) in basal ChAT activity compared with cells transfected
      with vector alone. By immunocytochemistry, a similar decrease in ChAT protein
      levels was found in the mutant transfectants. In cells differentiated with nerve
      growth factor, ChAT activity was again markedly lower in L286V-expressing cells
      than in control cells. We also observed reductions in ChAT activity in PC12 cells
      expressing the wild-type human PS-1 gene but to a lesser extent than in L286V
      expressing cells. The viability of cells transfected with either the wild-type or
      the mutant PS-1 gene was not compromised. Our results suggest that PS-1 mutations
      may contribute to the cognitive impairment in AD by causing a nontoxic
      suppression of the cholinergic phenotype.

PMID- 9278389
TI  - Transcriptional regulation of apolipoprotein A-I gene expression by the nuclear
      receptor RORalpha.
AB  - Since elevated concentrations of plasma high density lipoprotein (HDL) and its
      major apolipoprotein (apo), apoA-I, confer protection against atherosclerosis,
      considerable research efforts have focussed on the identification of factors
      regulating apoA-I gene expression in an attempt to increase its production.
      Nuclear receptors are interesting candidates because they are transcription
      factors whose activity is ligand-dependent. In the present study we identified
      the orphan receptor RORalpha1 as an activator of apoA-I gene transcription. In
      apoA-I-expressing intestinal Caco-2 cells, overexpression of the RORalpha1, but
      not the RORalpha2 or RORalpha3 isoforms, increased rat apoA-I gene transcription.
      Deletion and site-directed mutagenesis experiments identified a functional ROR
      responsive element (RORE) in the rat and mouse apoA-I gene promoters, which
      overlaps with the TATA box. Gel shift experiments indicated that this RORE binds
      the RORalpha1 isoform, but not the RORalpha2 or RORalpha3 isoforms. Furthermore,
      compared with wild type mice, apoA-I mRNA levels were significantly lower in
      small intestines of staggerer mice homozygous for a deletion in the RORalpha
      gene. In addition, reverse transcriptase-polymerase chain reaction analysis
      revealed the expression of RORalpha in small intestinal epithelium and in Caco-2
      cells. These data indicate a novel, physiological role for RORalpha1 in the
      regulation of genes involved in lipid and lipoprotein metabolism and possibly in
      the development of metabolic diseases, such as atherosclerosis.

PMID- 9278390
TI  - Tissue-specific expression of the Na,K-ATPase beta3 subunit. The presence of
      beta3 in lung and liver addresses the problem of the missing subunit.
AB  - The Na,K-ATPase belongs to a family of P-type ion-translocating ATPases sharing
      homologous catalytic subunits (alpha) that traverse the membrane several times
      and contain the binding sites for ATP and cations. In this family, only Na,K- and
      H,K-ATPases have been shown to have a second subunit, a single-span glycoprotein
      called beta. Recently a new isoform (beta3) has been identified in mammals. Here
      we describe structural features and tissue distribution of the beta3 protein,
      utilizing an antiserum specific for its N terminus. beta3 was the only beta
      detected in Na,K-ATPase purified from C6 glioma. Treatment with N-glycosidase F
      confirmed that beta3 is a glycoprotein containing N-linked carbohydrate chains.
      Molecular masses of the glycosylated protein and core protein were estimated to
      be 42 and 35 kDa, respectively, which are different from those of the beta1 and
      beta2 subunits. Detection of beta subunits has historically been difficult in
      certain tissues. Sensitivity was improved by deglycosylating, and expression was
      evaluated by obtaining estimates of beta3/alpha ratio. The proportion of beta3
      protein in the rat was highest in lung and testis. It was also present in liver
      and skeletal muscle, whereas kidney, heart, and brain contained it only as a
      minor component of the Na,K-ATPase. In P7 rat, we found skeletal muscle and lung
      Na,K-ATPase to be the most enriched in beta3 subunit, whereas expression in liver
      was very low, illustrating developmentally regulated changes in expression. The
      substantial expression in lung and adult liver very likely explains long-standing
      puzzles about an apparent paucity of beta subunit in membranes or in discrete
      cellular or subcellular structures.

PMID- 9278391
TI  - The sequence of the alternatively spliced sixth exon of alpha-tropomyosin is
      critical for cooperative actin binding but not for interaction with troponin.
AB  - Tropomyosins, a family of highly conserved coiled-coil actin binding proteins,
      can differ as a consequence of alternative expression of several exons (Lees
      Miller, J., and Helfman, D. (1991) BioEssays 13, 429-437). Exon 6, which encodes
      residues 189-213 in long, 284-residue tropomyosins, has two alternative forms,
      exon 6a or 6b, both highly conserved throughout evolution. In alpha-tropomyosin,
      exon 6a or 6b is not specific to any one of the nine isoforms. Exon 6b encodes
      part of a putative Ca2+-sensitive troponin binding site in striated muscle
      tropomyosins, suggesting that the exon 6-encoded region may be specialized for
      certain tropomyosin functions. A series of recombinant, unacetylated tropomyosin
      exon 6 deletion and substitution mutants and chimeras was expressed in
      Escherichia coli to determine the requirements of exon 6 for tropomyosin
      function. Functional properties of the tropomyosins were defined by actin
      affinity measured by cosedimentation, troponin T affinity using a newly developed
      biosensor assay, and regulation of the actomyosin MgATPase. The region of
      tropomyosin encoded by exon 6 affects actin affinity but not thin filament
      assembly, troponin T binding, or regulation with troponin. The tropomyosins with
      exon 6a or 6b function normally whether a striated muscle exon 9a or smooth/non
      muscle exon 9d is present. However, the effect of deleting 21 amino acids encoded
      by exon 6 or replacing it with a GCN4 leucine zipper sequence depends on the COOH
      terminal sequence.

PMID- 9278392
TI  - Cysteine sulfinate desulfinase, a NIFS-like protein of Escherichia coli with
      selenocysteine lyase and cysteine desulfurase activities. Gene cloning,
      purification, and characterization of a novel pyridoxal enzyme.
AB  - Selenocysteine lyase (EC 4.4.1.16) exclusively decomposes selenocysteine to
      alanine and elemental selenium, whereas cysteine desulfurase (NIFS protein) of
      Azotobacter vinelandii acts indiscriminately on both cysteine and selenocysteine
      to produce elemental sulfur and selenium respectively, and alanine. These
      proteins exhibit some sequence homology. The Escherichia coli genome contains
      three genes with sequence homology to nifS. We have cloned the gene mapped at
      63.4 min in the chromosome and have expressed, purified to homogeneity, and
      characterized the gene product. The enzyme comprises two identical subunits with
      401 amino acid residues (Mr 43,238) and contains pyridoxal 5'-phosphate as a
      coenzyme. The enzyme catalyzes the removal of elemental sulfur and selenium atoms
      from L-cysteine, L-cystine, L-selenocysteine, and L-selenocystine to produce L
      alanine. Because L-cysteine sulfinic acid was desulfinated to form L-alanine as
      the preferred substrate, we have named this new enzyme cysteine sulfinate
      desulfinase. Mutant enzymes having alanine substituted for each of the four
      cysteinyl residues (Cys-100, Cys-176, Cys-323, and Cys-358) were all active. Cys
      358 corresponds to Cys-325 of A. vinelandii NIFS, which is conserved among all
      NIFS-like proteins and catalytically essential (Zheng, L., White, R. H., Cash, V.
      L., and Dean, D. R. (1994) Biochemistry 33, 4714-4720), is not required for
      cysteine sulfinate desulfinase. Thus, the enzyme is distinct from A. vinelandii
      NIFS in this respect.

PMID- 9278393
TI  - Cloning and characterization of the type I inositol 1,4,5-trisphosphate receptor
      gene promoter. Regulation by 17beta-estradiol in osteoblasts.
AB  - The inositol 1,4,5-trisphosphate (InsP3) receptor is essential for signal Ca2+
      release from intracellular stores and for capacitative Ca2+ entry. We have
      isolated the promoter and proximal DNA segments of the human type I InsP3
      receptor gene. Transcription initiation in human G-292 osteosarcoma and HL-60
      promyelocytic leukemia cells was shown to occur predominantly from an adenine
      residue located 39 base pairs downstream of a consensus TATA box element.
      Upstream DNA including the TATA box promoted directional transcription of a
      chloramphenicol acetyltransferase reporter gene when transfected into G-292
      cells. A negative regulatory element in the distal promoter and a positive
      element in the proximal region were identified by deletion mapping and
      transcription assays. The proximal region enhanced transcription in response to
      12-O-tetradecanoylphorbol-13-acetate or serum, but conferred transcriptional
      repression in response to 1,25-dihydroxyvitamin D3 or 17beta-estradiol. The
      repressive effect of 17beta-estradiol was mediated by the nuclear estrogen
      receptor, as estrogen-dependent transcriptional repression was inhibited by the
      antiestrogen tamoxifen and the estrogen receptor antagonist ICI 182,780. This is
      the first study of the type I InsP3 receptor gene promoter, and the results
      suggest a mechanism by which chronic estrogen treatment of osteoblasts affects
      type I InsP3 receptor gene expression, signal transduction, and secretion.

PMID- 9278395
TI  - Sequence-specific DNA binding and transcriptional regulation by the promyelocytic
      leukemia zinc finger protein.
AB  - Chromosomal translocation t(11;17)(q23;21) is associated with a retinoic acid
      resistant form of acute promyelocytic leukemia. The translocation fuses the
      RARalpha gene to the PLZF gene, resulting in the formation of reciprocal fusion
      proteins, hypothesized to play prominent roles in leukemogenesis. Promyelocytic
      leukemia zinc finger (PLZF) encodes a transcription factor with nine Kruppel-like
      zinc fingers, seven of which are retained in the t(11;17) fusion protein RARalpha
      PLZF. We identified a specific DNA-binding site for the PLZF protein and showed
      that PLZF binds to this site through its most carboxyl seven zinc fingers. In co
      transfection experiments, PLZF repressed transcription through its cognate
      binding site. This repression function of PLZF was mapped to two regions on the
      protein, including the evolutionarily conserved POZ domain. In contrast, the
      RARalpha-PLZF protein activated transcription of a promoter containing a PLZF
      response element. These results suggest that RARalpha-PLZF, generated in acute
      promyelocytic leukemia, is an aberrant transcription factor that can deregulate
      the expression of PLZF target genes and contribute to leukemogenesis.

PMID- 9278394
TI  - Sites of reaction of the gastric H,K-ATPase with extracytoplasmic thiol reagents.
AB  - The vesicular gastric H,K-ATPase catalyzes an electroneutral H for K exchange
      allowing acidification of the intravesicular space. There is a total of 28
      cysteines present in the alpha subunit of the gastric H,K-ATPase, of which 10 are
      found in the predicted transmembrane segments and their connecting loop, and 9
      are present in the beta subunit, of which 6 are disulfide-linked. To determine
      which of these was accessible to extracytoplasmic attack, the enzyme was
      inhibited by four different substituted 2-pyridylmethylsulfinyl benzimidazoles, 5
      methoxy-2-[(4-methoxy-3, 5-dimethyl-2-pyridyl)methylsulfinyl]-1H-benzimidazole
      (omeprazole), 2-[(4-trifluoroethoxy-3-methyl-2-pyridyl)methylsulfinyl]-1H-ben
      zimida zole (lansoprazole), 5-difluoromethoxy-2-[3, 4-methoxy-2
      pyridyl)methylsulfinyl]-1H-benzimidazole (pantoprazole), and 2-[(4-(3
      methoxypropoxy)-3-methyl)-2-pyridyl)methylsulfinyl]-1H-++ +benzi midazole
      (rabeprazole), under acid transporting conditions. All of these compounds are
      weak bases that accumulate in the acidic space generated by the pump and undergo
      an acid catalyzed rearrangement to a cationic sulfenamide, which forms disulfides
      with accessible cysteines. The relative rates of acid activation of these
      compounds corresponded to the relative rates of inhibition of ATPase activity and
      acid transport. Fragmentation of the enzyme by trypsin followed by SDS
      polyacrylamide gel electrophoresis showed that omeprazole bound covalently to one
      of the two cysteines in the domains containing the fifth and sixth transmembrane
      segments and their extracytoplasmic loop and to cysteine 892 in the loop between
      the seventh and eighth transmembrane segments, but inhibition correlated with the
      reaction with cysteines in the fifth and sixth domain. Lansoprazole bound to the
      cysteines in these two domains as well as to cysteine 321 toward the
      extracytoplasmic end of the third transmembrane segments. Pantoprazole bound only
      to either cysteine 813 or 822 in the fifth and sixth transmembrane region. The
      inhibition of Rabeprazole correlated also with its binding to this part of the
      protein, but this compound continued to bind after full inhibition, eventually
      binding also to cysteines 321 and 892. No binding was found to any of the
      cysteines in the seventh to tenth transmembrane segments. Thermolysin digestion
      of the isolated omeprazole-labeled fifth and sixth transmembrane pair showed that
      cysteine 813 was the site of labeling. It is concluded that binding of these
      sided reagents to cysteine 813 in the loop between transmembrane (TM)5 and TM6 is
      sufficient for inhibition of ATPase activity and acid transport by the gastric
      acid pump. Of the 10 cysteines present in the membrane and extracytoplasmic
      domain, only three are exposed sufficiently to allow reactivity with these
      cationic thiol reagents. The binding to cysteine 813 defines the location of the
      extracytoplasmic loop between TM5 and TM6 and places the carboxylic acids 820 and
      824 conserved between the gastric H,K- and the Na,K-ATPases in TM6, consistent
      with their assumed role in cation binding.

PMID- 9278396
TI  - Improved activity and modulated action pattern obtained by random mutagenesis at
      the fourth beta-alpha loop involved in substrate binding to the catalytic
      (beta/alpha)8-barrel domain of barley alpha-amylase 1.
AB  - The functionality of the sequence Arg183-Gly184-Tyr185 of the substrate binding
      fourth beta-alpha loop in the (beta/alpha)8-barrel of barley alpha-amylase
      isozyme 1 (AMY1) was studied by random mutagenesis. A motif of polar Gly184
      hydrophobic residues was present in active mutants, selected by starch plate
      screening of yeast transformants. Gly184 was important, probably due to the
      carbonyl group binding to Ca2+ and the spatial proximity of Phe181. Mutation of
      both flanking residues as in Ser183-Gly184-Met185 (SGM-) and TGL-AMY1 decreased
      the Ca2+ affinity. SGM-AMY1 has 2-fold increased activity for amylose but reduced
      activity on maltooligosaccharides, whereas KGY-AMY1 has up to 3-fold elevated
      activity toward the oligosaccharides. TGL-AMY1 has modest activity on all
      substrates. Shifted action pattern on maltooligosaccharides for NGY-, SGM-, and
      TGL-AMY1 support that Arg183 in wild type is located at subsites +1 and +2,
      accommodating two sugar rings toward the reducing end from the site of cleavage.
      In the crystal structure of barley alpha-amylase 2 (AMY2), Lys182 (equivalent to
      AMY1 Arg183) is hydrogen-bonded with sugar OH-3 in subsite +2. Higher Ki app for
      acarbose inhibition of KGY-AMY1 and parent AMY1 compared with the other mutants
      suggests favorable substrate interactions for Arg/Lys183. KGY-AMY1 was not
      inhibited by the AMY2-specific proteinaceous barley alpha-amylase/subtilisin
      inhibitor, although Lys182 of AMY2 is salt-linked to the inhibitor.

PMID- 9278397
TI  - Purification of a fatty acid-stimulated protein-serine/threonine phosphatase from
      bovine brain and its identification as a homolog of protein phosphatase 5.
AB  - An arachidonic acid-stimulated Ser/Thr phosphatase activity was detected in
      soluble extracts prepared from rat pituitary clonal GH4C1 cells, rat or bovine
      brain, and bovine heart. The enzyme activity was purified to homogeneity from
      bovine brain as a monomer with a Mr of 63,000 and a specific activity of 32 nmol
      of Pi released per min/mg of protein when assayed in the presence of 10 microM
      phosphocasein in the absence of lipid. Arachidonic acid stimulated activity 4-14
      fold, with half-maximal stimulation at 50-100 microM, when assayed in the
      presence of a variety of phosphosubstrates including casein, reduced
      carboxamidomethylated and maleylated lysozyme, myelin basic protein, and histone.
      Oleic acid, linoleic acid, and palmitoleic acid also stimulated activity;
      however, saturated fatty acids and alcohol or methyl ester derivatives of fatty
      acids did not significantly affect activity. The lipid-stimulated phosphatase was
      identified as the bovine equivalent of protein phosphatase 5 or a closely related
      homolog by sequence analysis of proteolytic fragments generated from the purified
      enzyme. When recombinant rat protein phosphatase 5 was expressed as a cleavable
      glutathione S-transferase fusion protein, the affinity-purified thrombin-cleaved
      enzyme exhibited a specific activity and sensitivity to arachidonic acid similar
      to those of the purified bovine brain enzyme. These results suggest that protein
      phosphatase 5 may be regulated in vivo by a lipid second messenger or another
      endogenous activator.

PMID- 9278398
TI  - How does alendronate inhibit protein-tyrosine phosphatases?
AB  - Alendronate (4-amino-1-hydroxybutylidene 1,1-bisphosphonate) is a drug used in
      the treatment of osteoporosis and other bone diseases. The inhibition of protein
      tyrosine phosphatases (PTPs) by alendronate suggests that PTPs may be molecular
      targets. As a clear understanding of the inhibition mechanism is lacking, our aim
      was to analyze the mechanism to provide further insight into its therapeutic
      effect. We show here that the inhibition of PTPs by alendronate in the presence
      of calcium followed first-order kinetic behavior, and kinetic parameters for the
      process were determined. Evidence is presented that the inhibition by
      alendronate/calcium is active site-directed. However, this process was very
      sensitive to assay constituents such as EDTA and dithiothreitol. Furthermore, the
      inhibition of PTPs by alendronate/calcium was eliminated by the addition of
      catalase. These observations suggest that a combination of alendronate, metal
      ions, and hydrogen peroxide is responsible for the inhibition of PTPs. The
      individual effects of alendronate, calcium, or hydrogen peroxide on the
      inactivation of CD45 were determined. Electrospray ionization mass spectrometry
      demonstrated that the mass of PTP1B increased by 34 +/- 2 units after the enzyme
      was inactivated with alendronate/calcium, due to the oxidization of the catalytic
      cysteine to sulfinic acid (Cys-SO2H). The inhibited PTP1B could be partially
      reactivated by treatment with reducing agents such as hydroxylamine (NH2OH) and
      N,N'-dimethyl-N, N'-bis(mercaptoacetyl)hydrazine, indicating the presence of
      other oxidized forms such as sulfenic acid (Cys-SOH). This further confirms that
      the inhibition is the result of oxidation of the catalytic cysteine. The
      relevance of this oxidative inhibition mechanism in a biological system is
      discussed.

PMID- 9278399
TI  - Identification of an mRNA-binding protein and the specific elements that may
      mediate the pH-responsive induction of renal glutaminase mRNA.
AB  - Various segments of the 3'-nontranslated region of the renal glutaminase (GA)
      mRNA were tested for their ability to enhance turnover and pH responsiveness. The
      combined effects were retained in the 340-base R-2 segment. However, the combined
      R-1 and R-3 fragments also imparted a partial destabilization and pH
      responsiveness to a chimeric beta-globin mRNA. RNA electrophoretic mobility shift
      assays indicated that cytosolic extracts of rat renal cortex contain a protein
      that binds to the R-2 and R-3 RNAs. The binding observed with the R-2 RNA was
      mapped to a direct repeat of an 8-base AU sequence. This binding was effectively
      competed with an excess of the same RNA, but not by adjacent or unrelated RNAs.
      UV cross-linking experiments identified a 48-kDa protein that binds to the AU
      repeats of the R-2 RNA. The apparent binding of this protein was greatly reduced
      in renal cytosolic extracts prepared from acutely acidotic rats. Two related RNA
      sequences in the R-3 segment also exhibited specific binding. However, the latter
      binding was more effectively competed by R-2 RNA than by itself, indicating that
      the homologous sites may be weaker binding sites for the same 48-kDa protein.
      Thus, a single protein may bind specifically to multiple instability elements
      within the 3'-nontranslated region of the GA mRNA and mediate its pH-responsive
      stabilization.

PMID- 9278400
TI  - Apolipoprotein B is intracellularly associated with an ER-60 protease homologue
      in HepG2 cells.
AB  - Two ALLN (N-acetyl-leucyl-leucyl-norleucinal)-sensitive endoplasmic reticulum
      (ER)-localized proteases (ER-60 and ER-72) were recently purified from rat liver.
      We used an antibody to rat ER-60 to investigate the possible role of this
      protease in apolipoprotein B (apoB) degradation. First, immunoprecipitation and
      immunoblotting experiments with the anti-rat ER-60 antibody suggested that HepG2
      cells contain a homologue of ER-60 with an approximate molecular mass of 58-60
      kDa. The ER-60 homologue was mostly associated with the luminal contents of HepG2
      microsomes. Evidence from co-immunoprecipitation and cross-linking experiments
      appear to suggest that the ER-60 homologue in HepG2 cells is associated with apoB
      intracellularly. A small pool of apoB was recovered when HepG2 lysates were
      subjected to immunoprecipitation with anti-rat ER-60 antibody followed by a
      second immunoprecipitation with anti-apoB antibody. Furthermore, cross-linking of
      permeabilized cells with dithiobis(succinimidylpropionate) further demonstrated
      association of apoB with the ER-60 homologue in HepG2 cells. Three polypeptides
      with molecular masses of 78, 66, and 50 kDa were consistently found to be
      associated with apoB as well as the 58-kDa ER-60 homologue. The 78-kDa protein
      associated with both apoB and ER-60 appeared to represent immunoglobulin heavy
      chain-binding protein (BiP) based on immunoprecipitation with a monoclonal
      antibody. Cross-linking and immunoblotting experiments suggested the association
      of the 78-kDa BiP with both the 58-kDa ER-60 homologue as well as the 550-kDa
      apoB. In summary, the data suggests that HepG2 cells contain a 58-kDa protein
      which is homologous to the rat liver ER-60 in size, antigenecity, and
      intracellular localization. The ER-60 homologue in HepG2 cells appears to be
      closely associated with apoB, as well as other proteins possibly representing ER
      chaperones such as BiP. We hypothesize that the ER-60 homologue may be involved
      in the degradation of apoB in the ER lumen of HepG2 cells.

PMID- 9278401
TI  - Glucose-6-P control of glycogen synthase phosphorylation in yeast.
AB  - The SNF1 gene encodes a protein kinase necessary for expression of glucose
      repressible genes and for the synthesis of the storage polysaccharide glycogen.
      From a genetic screen, we have found that mutation of the PFK2 gene, which
      encodes the beta-subunit of 6-phosphofructo-1-kinase, restores glycogen
      accumulation in snf1 cells. Loss of PFK2 causes elevated levels of metabolites
      such as glucose-6-P, hyperaccumulation of glycogen, and activation of glycogen
      synthase, whereas glucose-6-P is reduced in snf1 cells. Other mutations that
      increase glucose-6-P, deletion of PFK1, which codes for the alpha-subunit of 6
      phosphofructo-1-kinase, or of PGI1, the phosphoglucoisomerase gene, had similar
      effects on glycogen metabolism as did pfk2 mutants. We propose that elevated
      glucose-6-P mediates the effects of these mutations on glycogen storage. Glycogen
      synthase kinase activity was reduced in extracts from pfk2 cells but was restored
      to that of wild type if the extract was gel-filtered to remove small molecules.
      Also, added glucose-6-P inhibited the glycogen synthase kinase activity in
      extracts from wild-type cells, half-maximally at approximately 2 mM. We suggest
      that glucose-6-P controls glycogen synthase activity by two separate mechanisms.
      First, glucose-6-P is a direct activator of glycogen synthase, and second, it
      controls the phosphorylation state of glycogen synthase by inhibiting a glycogen
      synthase kinase.

PMID- 9278402
TI  - Studies on the redox centers of the terminal oxidase from Desulfovibrio gigas and
      evidence for its interaction with rubredoxin.
AB  - Rubredoxin-oxygen oxidoreductase (ROO) is the final component of a soluble
      electron transfer chain that couples NADH oxidation to oxygen consumption in the
      anaerobic sulfate reducer Desulfovibrio gigas. It is an 86-kDa homodimeric
      flavohemeprotein containing two FAD molecules, one mesoheme IX, and one Fe
      uroporphyrin I per monomer, capable of fully reducing oxygen to water. EPR
      studies on the native enzyme reveal two components with g values at approximately
      2.46, 2.29, and 1.89, which are assigned to low spin hemes and are similar to the
      EPR features of P-450 hemes, suggesting that ROO hemes have a cysteinyl axial
      ligation. At pH 7.6, the flavin redox transitions occur at 0 +/- 15 mV for the
      quinone/semiquinone couple and at -130 +/- 15 mV for the semiquinone/hydroquinone
      couple; the hemes reduction potential is -350 +/- 15 mV. Spectroscopic studies
      provided unequivocal evidence that the flavins are the electron acceptor centers
      from rubredoxin, and that their reduction proceed through an anionic semiquinone
      radical. The reaction with oxygen occurs in the flavin moiety. These data are
      strongly corroborated by the finding that rubredoxin and ROO are located in the
      same polycistronic unit of D. gigas genome. For the first time, a clear role for
      a rubredoxin in a sulfate-reducing bacterium is presented.

PMID- 9278403
TI  - Negatively charged anabaena flavodoxin residues (Asp144 and Glu145) are important
      for reconstitution of cytochrome P450 17alpha-hydroxylase activity.
AB  - Catalysis by microsomal cytochromes P450 requires the membrane-bound enzyme NADPH
      cytochrome P450 reductase (P450 reductase), which transfers electrons to the P450
      heme via a flavodoxin-like domain. Previously, we reported that Escherichia coli
      flavodoxin (Fld), a soluble electron transfer protein, directly interacts with
      bovine cytochrome P450 17alpha-hydroxylase/17,20-lyase (P450c17) and donates
      electrons to this enzyme when reconstituted with NADPH-ferredoxin (flavodoxin)
      reductase (FNR) (Jenkins, C. M., and Waterman, M. R. (1994) J. Biol. Chem. 269,
      27401-27408). To investigate whether flavodoxins can serve as useful models of
      the analogous domain in P450 reductase, we have examined the FNR-Fld system from
      the cyanobacterium Anabaena. Mutagenesis of two acidic Anabaena Fld residues
      (D144A and E145A) significantly decreased flavodoxin-supported P450c17
      progesterone 17alpha-hydroxylase activity. Specifically, D144A exhibited only 15%
      of the activity of wild-type Fld, whereas the adjacent mutation, E145A, caused a
      40% loss in activity. P450-dependent hydrogen peroxide/superoxide production by
      wild-type FNR-Fld was measurably higher than that generated by FNR-D144A or FNR
      E145A, indicating that the mutations do not lead to P450 heme-mediated electron
      uncoupling. Interestingly, the D144A and E145A mutants bind with equal or even
      greater affinity to P450c17 than wild-type Fld. Furthermore, these mutations
      (D144A and E145A) actually increased cytochrome c reductase activity (35 and 100%
      higher than wild type). Anabaena Fld residues Asp144 and Glu145 align closely
      with rat P450 reductase residue Asp208, which has been shown by mutagenesis to be
      important in electron transfer to P4502B1 but not to cytochrome c (Shen, A. L.,
      and Kasper, C. B. (1995) J. Biol. Chem. 270, 27475-27480). Thus, these residues
      in flavodoxins and P450 reductase appear to have similar functions in P450
      recognition and/or electron transfer, supporting the hypothesis that flavodoxins
      represent valid models for the FMN-binding domain of P450 reductase.

PMID- 9278404
TI  - Kinetic isotope effects and electron transfer in the reduction of xanthine
      oxidoreductase with 4-hydroxypyrimidine. A comparison between oxidase and
      dehydrogenase forms.
AB  - Isolated from bovine milk, xanthine oxidase (XO) and xanthine dehydrogenase (XDH)
      are two interconvertible forms of the same protein, differing in the number of
      protein cysteines versus cystines. Most differences between XO and XDH are
      localized to the FAD center, the site at which the oxidizing substrates NAD and
      molecular oxygen react. A comparative study of the reduction of XO and XDH has
      been performed to assess differences in reactivity of the molybdopterin site, as
      well as subsequent electron-transfer events from molybdenum to 2Fe/2S and FAD
      centers. The compound 4-hydroxypyrimidine (4-OH-P) was chosen as reducing
      substrate because its higher Km value raised the possibility of binding weak
      enough to measure kinetically, and its high kcat value could allow detection of
      intramolecular electron-transfer reactions. As measured by stopped flow
      spectrophotometry, XO and XDH react with the first equivalent of 4-OH-P via
      similar mechanisms, differing in the magnitude of rate and dissociation
      constants. Using [2-2H]4-OH-P as substrate, a D(k/Kd) isotope effect of 1.9 to
      2.3 suggests that movement of the hydrogen abstracted from substrate appreciably
      limits the rate of initial enzyme reduction from Mo(VI) to Mo(IV). Monitoring the
      visible spectrum of the enzymes, the first observed step is reduction of a single
      2Fe/2S center and presumably re-oxidation of Mo(IV) to Mo(V). This suggests a
      common pathway for electron transfer involving reduction of a 2Fe/2S center prior
      to reduction of the second 2Fe/2S and FAD centers. Rates of the first electron
      transfer from molybdenum to the 2Fe/2S center are rapid, 290 s-1 with XO and 180
      s-1 with XDH, and are consistent with rates measured by flash photolysis (Walker,
      M. C., Hazzard, J. T., Tollin, G., and Edmondson, D. E. (1991) Biochemistry 30,
      5912-5917) allowing discrete observation of the electron-transfer reactions that
      occur during turnover. This step also exhibits a modest primary kinetic isotope
      effect of 1.5 to 1.6 when [2-2H]4-OH-P is used, possibly due to deprotonation of
      the molybdenum center prior to electron transfer. A second one-electron transfer,
      presumably oxidizing Mo(V) to Mo(VI), follows in a step coincident with product
      dissociation, consistent with a role for product release in controlling electron
      transfer events. The kinetics of this complex system are described and
      interpreted quantitatively in models that are consistent with all the data.

PMID- 9278405
TI  - Nm23/PuF does not directly stimulate transcription through the CT element in
      vivo.
AB  - Decreased levels of the nm23 gene product have been correlated with increased
      tumor metastatic potential in a variety of malignancies. At least a subset of the
      regulatory properties of Nm23 has been proposed to be due to transactivation of
      the human c-myc oncogene through binding to a homopyrimidine tract 140 base pairs
      upstream of the transcription start site (termed the CT element or the PuF site).
      Conventional transcription factors possess DNA binding and transactivation
      domains; Nm23 fusion proteins were used to address two questions. First, if
      provided with a well characterized DNA binding domain, does Nm23 possess a
      transactivation domain capable of stimulating transcription of an appropriate
      reporter? Second, if provided with a potent transactivation domain, is the DNA
      binding of Nm23 of sufficient specificity and affinity to direct the fusion
      protein to a CT-dependent reporter? Since reporter gene expression was not
      stimulated in either case, we conclude that Nm23 does not directly stimulate
      transcription through binding to the CT element and that its antimetastatic and
      other reported functions are likely due to other biochemical activities.

PMID- 9278406
TI  - Differential targeting of nicotinic acetylcholine receptors by novel alphaA
      conotoxins.
AB  - We describe the isolation and characterization of two peptide toxins from Conus
      ermineus venom targeted to nicotinic acetylcholine receptors (nAChRs). The
      peptide structures have been confirmed by mass spectrometry and chemical
      synthesis. In contrast to the 12-18 residue, 4 Cys-containing alpha-conotoxins,
      the new toxins have 30 residues and 6 Cys residues. The toxins, named alphaA
      conotoxins EIVA and EIVB, block both Torpedo and mouse alpha1-containing muscle
      subtype nAChRs expressed in Xenopus oocytes at low nanomolar concentrations. In
      contrast to alpha-bungarotoxin, alphaA-EIVA is inactive at alpha7-containing
      nAChRs even at micromolar concentrations. In this regard, alphaA-EIVA is similar
      to the previously described alpha-conotoxins (e.g. alpha-MI and alpha-GI) which
      also selectively target alpha1- versus alpha7-containing nAChRs. However, alpha
      MI and alpha-GI discriminate between the alpha/delta versus alpha/gamma subunit
      interfaces of the mouse muscle nAChR with 10,000-fold selectivity. In contrast,
      alphaA-conotoxin EIVA blocks both the alpha/gamma site and alpha/delta site with
      equally high affinity but with distinct kinetics. The alphaA-conotoxins thus
      represent novel probes for the alpha/gamma as well as the alpha/delta binding
      sites of the nAChR.

PMID- 9278407
TI  - Integrin-mediated activation of focal adhesion kinase is independent of focal
      adhesion formation or integrin activation. Studies with activated and inhibitory
      beta3 cytoplasmic domain mutants.
AB  - Integrin alphaIIbbeta3 functions as the fibrinogen receptor on platelets and
      mediates platelet aggregation and clot retraction. Among the events that occur
      during either "inside-out" or "outside-in" signaling through alphaIIbbeta3 is the
      phosphorylation of focal adhesion kinase (pp125(FAK)) and the association of
      pp125(FAK) with cytoskeletal components. To examine the role of pp125(FAK) in
      these integrin-mediated events, pp125(FAK) phosphorylation and association with
      the cytoskeleton was determined in cells expressing two mutant forms of
      alphaIIbbeta3: alphaIIbbeta3(D723A/E726A), a constitutively active integrin in
      which the putative binding site for pp125(FAK) is altered, and
      alphaIIbbeta3(F727A/K729E/F730A), in which the putative binding site for alpha
      actinin is altered. Both mutants were expressed on the cell surface and were able
      to bind ligand, either spontaneously or upon activation. Whereas cells expressing
      alphaIIbbeta3(D723A/E726A) were able to form focal adhesions and stress fibers
      upon adherence to fibrinogen, cells expressing alphaIIbbeta3(F727A/K729E/F730A)
      adhere to fibrinogen, but had reduced focal adhesions and stress fibers.
      pp125(FAK) is recruited to focal adhesions in adherent cells expressing
      alphaIIbbeta3(D723A/E726A) and is phosphorylated in adherent cells or in cells in
      suspension in the presence of fibrinogen. In adherent cells expressing
      alphaIIbbeta3(F727A/K729E/F730A), pp125(FAK) was phosphorylated despite reduced
      formation of focal adhesions and stress fibers. We conclude that activation of
      pp125(FAK) can be dissociated from two important events in integrin signaling,
      the assembly of focal adhesions in adherent cells and integrin activation
      following ligand occupation.

PMID- 9278408
TI  - Transient electric birefringence study of intermediate filament formation from
      vimentin and glial fibrillary acidic protein.
AB  - Mg2+-induced polymerization of type III intermediate filament proteins vimentin
      and glial fibrillary acidic protein was studied by transient electric
      birefringence. In the absence of MgCl2 we found a net permanent dipole moment,
      approximately 45-nm-long dimers for vimentin, approximately 65-nm-long tetramers,
      hexamers, and possibly octamers for both proteins, and 100-nm aggregates for
      glial fibrillary acidic protein. Controlled oligomerization occurred after the
      addition of MgCl2. Although the solutions contained (small) aggregates of
      different sizes, more or less discrete steps in polymer formation were observed,
      and it was possible to discriminate between an increase in width and length. At
      the first stage of polymerization (in 0.3 mM MgCl2 for vimentin and 0.2 mM MgCl2
      for glial fibrillary acidic protein), the permanent dipole moment disappeared
      without a change in length of the particles. At higher MgCl2 concentrations,
      structures of approximately 100 nm were formed, which strongly tended to
      laterally assemble into full-width intermediate filament structures consisting of
      about 32 monomers. This contrasts with previous models where first full-width
      (approximately 10-nm) aggregates are formed, which then increase in length.
      Subsequently, two discrete elongation steps of 35 nm are observed that increase
      the length to 135 and 170 nm, respectively. Possible structural models are
      suggested for the polymerization.

PMID- 9278409
TI  - Thioredoxin domain non-equivalence and anti-chaperone activity of protein
      disulfide isomerase mutants in vivo.
AB  - Coexpression of the enzyme, protein disulfide isomerase (PDI), has been shown to
      increase soluble and secreted IgG levels from baculovirus-infected insect cells
      (Hsu, T.-A., Watson, S., Eiden, J. J., and Betenbaugh, M. J. (1996) Protein
      Expression Purif. 7, 281-288). PDI is known to include catalytic active sites in
      two separate thioredoxin-like domains, one near the amino terminus and another
      near the carboxyl terminus. To examine the role of these catalytic active sites
      in enhancing immunoglobulin solubility, baculovirus constructs were utilized with
      cysteine to serine mutations at the first cysteine of one or both of the CGHC
      active site sequences. Trichoplusia ni insect cells were coinfected with a
      baculovirus vector coding for IgG in concert with either the wild-type human PDI
      virus, amino-terminal mutant (PDI-N), carboxyl-terminal mutant (PDI-C), or mutant
      with both active sites altered (PDI-NC). Western blot analysis revealed that both
      immunoglobulins and PDI protein were expressed in the coinfected cells. To
      evaluate the effect of the PDI variants on immunoglobulin solubility and
      secretion, the infected cells were labeled with 35S-amino-acids for different
      periods, and the soluble immunoglobulins were immunoprecipitated from clarified
      cell lysates and culture medium using anti-IgG antibodies. Only coinfections with
      the wild-type PDI and PDI-N mutant led to increased immunoglobulin solubility and
      higher IgG secretion. In contrast, infection with the PDI-C and PDI-NC variants
      actually lowered immunoglobulin solubility levels below those achieved with a
      negative control virus. Immunoprecipitation with anti-PDI antibody revealed that
      heterologous PDI-C and PDI-NC were insoluble, even though PDI-N and wild-type PDI
      protein were detected in soluble form. The capacity for PDI-N to increase
      immunoglobulin solubility whereas the PDI-C mutant lowered solubility indicates
      that the amino- and carboxyl-terminal thioredoxin domains of PDI are functionally
      distinct in vivo following mutations to the active site. Furthermore, mutations
      at the active site of the carboxyl-terminal thioredoxin domain result in PDI
      variants that can act as anti-chaperones of immunoglobulin solubility in vivo as
      has been observed in vitro for lysozyme aggregation by wild-type PDI and PDI
      mutants (Puig, A., and Gilbert, H. F. (1994) J. Biol. Chem. 269, 7764-7771).

PMID- 9278410
TI  - Cell-specific expression and regulation of a glucokinase gene locus transgene.
AB  - Transgenic mice containing one or more extra copies of the entire glucokinase
      (GK) gene locus were generated and characterized. The GK transgene, an 83
      kilobase pair mouse genomic DNA fragment containing both promoter regions, was
      expressed and regulated in a cell-specific manner, and rescued GK null lethality
      when crossed into mice bearing a targeted mutation of the endogenous GK gene.
      Livers from the transgenic mice had elevated GK mRNA, protein, and activity
      levels, compared with controls, and the transgene was regulated in liver by
      dietary manipulations. The amount of GK immunoreactivity in hepatocyte nuclei,
      where GK binds to the GK regulatory protein, was also increased. Pancreatic
      islets displayed increased GK immunoreactivity and NAD(P)H responses to glucose,
      but only when isolated and cultured in 20 mM glucose, as a result of the
      hypoglycemic phenotype of these mice (Niswender, K. D., Shiota, M., Postic, C.,
      Cherrington, A. D., and Magnuson, M. A. (1997) J. Biol. Chem. 272, 22604-22609).
      Together, these results indicate that the region of the gene from -55 to +28
      kilobase pairs (relative to the liver GK transcription start site) contains all
      the regulatory sequences necessary for expression of both GK isoforms, thereby
      placing an upper limit on the size of the GK gene locus.

PMID- 9278411
TI  - Effects of increased glucokinase gene copy number on glucose homeostasis and
      hepatic glucose metabolism.
AB  - The relationship between glucokinase (GK) gene copy number and glucose
      homeostasis was studied in transgenic mice with additional copies of the entire
      GK gene locus (Niswender, K. D., Postic, C., Jetton, T. L., Bennett, B. D.,
      Piston, D. W., Efrat, S., and Magnuson, M. A. (1997) J. Biol. Chem. 272, 22564
      22569). The plasma glucose concentration was reduced by 25 +/- 3% and 37 +/- 4%
      in mice with one or two extra copies of the gene locus, respectively. The basis
      for the hypoglycemic phenotype was determined using metabolic tracer techniques
      in chronically cannulated, conscious mice with one extra GK gene copy. Under
      basal conditions (6-h fasted) transgenic mice had a lower blood glucose
      concentration (-12 +/- 1%) and a slightly higher glucose turnover rate (+8 +/-
      3%), resulting in a significantly higher glucose clearance rate (+21 +/- 2%).
      Plasma insulin levels were not different, suggesting that increased glucose
      clearance was due to augmented hepatic, not islet, GK gene expression. Under
      hyperglycemic clamp conditions the transgenic mice had glucose turnover and
      clearance rates similar to the controls, but showed a lower plasma insulin
      response (-48 +/- 5%). Net hepatic glycogen synthesis was markedly elevated
      (+360%), whereas skeletal muscle glycogen synthesis was decreased (-40%). These
      results indicate that increased GK gene dosage leads to increased hepatic glucose
      metabolism and, consequently, a lower plasma glucose concentration. Increased
      insulin secretion was not observed, even though the transgene is expressed in
      islets, because hypoglycemia causes a down-regulation in islet GK content
      (Niswender, K. D., Postic, C., Jetton, T. L., Bennett, B. D., Piston, D. W.,
      Efrat, S., and Magnuson, M. A. (1997) J. Biol. Chem. 272, in press).

PMID- 9278412
TI  - Overexpression of nreB, a new GATA factor-encoding gene of Penicillium
      chrysogenum, leads to repression of the nitrate assimilatory gene cluster.
AB  - To investigate the mechanism of nitrogen metabolite repression in the
      biotechnologically important fungus Penicillium chrysogenum a polymerase chain
      reaction approach was employed to identify transcription factors involved in this
      regulatory circuit, leading to the isolation of a new gene (nreB) encoding a 298
      amino acid protein. Despite a low overall amino acid sequence identity of
      approximately 30%, it shares several features with Dal80p/Uga43p and Gzf3p/Nil2p,
      both repressors in nitrogen metabolism in Saccharomyces cerevisiae. All three
      proteins contain an N-terminal GATA-type zinc finger motif, displaying 86% amino
      acid sequence identity, and a putative leucine zipper motif in the C terminus.
      Northern blot analysis revealed the presence of two nreB transcripts, 1.8 and 1.5
      kilobases in length, that differ in polyadenylation sites. The steady state level
      of both transcripts is subject to nitrogen metabolite repression. The putative
      DNA binding domain of NREB, expressed as a fusion protein in Escherichia coli,
      binds in vitro to GATA sites of its own 5'-upstream region as well as in the
      promoter of the nitrate assimilation gene cluster. Consistent with a role in the
      regulation of nitrogen metabolism, overexpression of nreB leads to repression of
      nitrate assimilatory genes. Hence, the simple view of nitrogen regulation by four
      GATA factors in yeast, but only one key regulator in filamentous ascomycetes
      seems no longer valid.

PMID- 9278413
TI  - Biochemical and molecular consequences of massive mitochondrial gene loss in
      different tissues of a mutant strain of Drosophila subobscura.
AB  - In the studied mutant strain of Drosophila subobscura, 78% of the mitochondrial
      genomes lost >30% of the coding region by deletion. The mutations was genetically
      stable. Despite this massive loss of mitochondrial genes, the mutant did not seem
      to be affected. Distribution of the two genome types, cell levels of
      mitochondrial DNA, steady-state concentrations of the mitochondrial gene
      transcripts, mitochondrial enzymatic activities, and ATP synthesis capacities
      were measured in the head, thorax, and abdomen fractions of the mutant strain in
      comparison with a wild type strain. Results indicate that the deleted genomes are
      detected in all fractions but to a lesser extent in the male and female abdomen.
      In all fractions, there is a 50% increase in cellular mitochondrial DNA content.
      Although there is a decrease in steady-state concentrations of mitochondrial
      transcripts of genes affected by deletion, this is smaller than expected. The
      variations in mitochondrial biochemical activities in the different fractions of
      the wild strain are upheld in the mutant strain. Activity of complex I (involved
      in mutation) nevertheless shows a decrease in all fractions; activity of complex
      III (likewise involved) shows little or no change; finally, mitochondrial ATP
      synthesis capacity is identical to that observed in the wild strain. This latter
      finding possibly accounts for the lack of phenotype. This mutant is a good model
      for studying mitochondrial genome alterations and the role of the nuclear genome
      in these phenomena.

PMID- 9278414
TI  - Creation and removal of embedded ribonucleotides in chromosomal DNA during
      mammalian Okazaki fragment processing.
AB  - Mammalian RNase HI has been shown to specifically cleave the initiator RNA of
      Okazaki fragments at the RNA-DNA junction, leaving a single ribonucleotide
      attached to the 5'-end of the downstream DNA segment. This monoribonucleotide can
      then be removed by the mammalian 5'- to 3'-exo-/endonuclease, a RAD2 homolog-1
      (RTH-1) class nuclease, also known as flap endonuclease-1 (FEN-1). Although FEN
      1/RTH-1 nuclease often requires an upstream primer for efficient activity, the
      presence of an upstream primer is usually inhibitory or neutral for removal of
      this 5'-monoribonucleotide. Using model Okazaki fragment substrates, we found
      that DNA ligase I can seal a 5'-monoribonucleotide into DNA. When both ligase and
      FEN-1/RTH-1 were present simultaneously, some of the 5'-monoribonucleotides were
      ligated into DNA, while others were released. Thus, a 5'-monoribonucleotide,
      particularly one that is made resistant to FEN-1/RTH-1-directed cleavage by
      extension of an inhibitory upstream primer, can be ligated into the chromosome,
      despite the presence of FEN-1/RTH-1 nuclease. DNA ligase I was able to seal
      different monoribonucleotides into the DNA for all substrates tested, with an
      efficiency of 1-13% that of ligating DNA. These embedded monoribonucleotides can
      be removed by the combined action of RNase HI, cutting on the 5'-side, and FEN
      1/RTH-1 nuclease, cleaving on the 3'-side. After FEN-1/RTH-1 action and extension
      by polymerization, DNA ligase I can join the entirely DNA strands to complete
      repair.

PMID- 9278415
TI  - The self-association and fibronectin-binding sites of fibulin-1 map to calcium
      binding epidermal growth factor-like domains.
AB  - Fibulin-1 is a modular glycoprotein with amino-terminal anaphylatoxin-like
      modules followed by nine epidermal growth factor (EGF)-like modules and,
      depending on alternative splicing, four possible carboxyl termini. Fibulin-1 has
      been shown to self-associate as well as to bind calcium, fibronectin (FN),
      laminin, nidogen, and fibrinogen. To map ligand-binding sites within fibulin-1,
      polypeptides corresponding to various regions of fibulin-1 were expressed
      recombinantly and evaluated for their capacity to bind calcium, FN, or fibulin-1.
      A calcium-binding site(s) was mapped to EGF-like modules 5-9. A fibulin-1 self
      association site was localized to EGF-like modules 5 and 6 (amino acid residues
      356-440), as was a binding site for FN. The self-association interaction mediated
      by this pair of modules involved calcium since divalent cation chelators reduced
      the binding affinity of the interaction. By contrast, FN binding to EGF-like
      modules 5 and 6 was unaffected by the presence of divalent cation chelators. It
      can be concluded that EGF-like modules 5 and 6 bind calcium and mediate homotypic
      interaction between EGF-like modules 5 and 6 present in different fibulin-1
      molecules and heterotypic interaction between EGF-like modules 5 and 6 and type
      III repeats 13 and 14 in FN. While additional binding sites for calcium or FN
      were not detected, another fibulin-1 self-association site was found within amino
      acid residues 30-173. However, unlike the self-association site in EGF-like
      modules 5 and 6, which was functional in the native protein, the amino-terminal
      site was cryptic and revealed only after the protein was denatured.

PMID- 9278416
TI  - Reduction of dehydroascorbate to ascorbate by the selenoenzyme thioredoxin
      reductase.
AB  - Recycling of ascorbate from its oxidized forms is essential to maintain stores of
      the vitamin in human cells. Whereas reduction of dehydroascorbate to ascorbate is
      thought to be largely GSH-dependent, we reconsidered the possibility that the
      selenium-dependent thioredoxin system might contribute to ascorbate regeneration.
      We found that purified rat liver thioredoxin reductase functions as an NADPH
      dependent dehydroascorbate reductase, with an apparent Km of 2. 5 mM for
      dehydroascorbate, and a kcat of 90 min-1. Addition of 2.8 microM purified rat
      liver thioredoxin lowered the apparent Km to 0.7 mM, without affecting the
      turnover (kcat of 71 min-1). Since thioredoxin reductase requires selenium, we
      tested the physiologic importance of this enzyme for dehydroascorbate reduction
      in livers from control and selenium-deficient rats. Selenium deficiency lowered
      liver thioredoxin reductase activity by 88%, glutathione peroxidase activity by
      99%, and ascorbate content by 33%, but did not affect GSH content. NADPH
      dependent dehydroascorbate reductase activity due to thioredoxin reductase, on
      the basis of inhibition by aurothioglucose, was decreased 88% in dialyzed liver
      cytosolic fractions from selenium-deficient rats. GSH-dependent dehydroascorbate
      reductase activity in liver cytosol was variable, but typically 2-3-fold that of
      NADPH-dependent activity. These results show that the thioredoxin system can
      reduce dehydroascorbate, and that this function is required for maintenance of
      liver ascorbate content.

PMID- 9278417
TI  - Metabolic activation of trans-4-hydroxy-2-nonenal, a toxic product of membrane
      lipid peroxidation and inhibitor of P450 cytochromes.
AB  - Lipid peroxidation in biological membranes is known to yield reactive aldehydes,
      of which trans-4-hydroxy-2-nonenal (HNE) is particularly cytotoxic. This
      laboratory previously reported that purified liver microsomal P450 cytochromes
      are directly inactivated to varying extents by HNE. We have now found a mechanism
      based reaction in which P450s are inactivated by HNE in the presence of molecular
      oxygen, NADPH, and NADPH-cytochrome P450 reductase. The sensitivity of the
      various isozymes in the two pathways is different as follows: P450 2B4 and the
      orthologous 2B1 are inactivated to the greatest extent and 2C3, 1A2, 2E1, and 1A1
      to a somewhat lesser extent by the pathway in which HNE undergoes metabolic
      activation. In contrast, 2B4 and 2B1 are insensitive to direct inactivation, and
      the reductase is unaffected by HNE by either route. Recent studies on the
      catalytic activities of the T302A mutant of P450 2B4 have shown that the rate of
      oxidation of a variety of xenobiotic aldehydes to carboxylic acids is decreased,
      but the rates of aldehyde deformylation and mechanism-based inactivation of the
      cytochrome are stimulated over those of the wild-type enzyme (Raner, G. M., Vaz,
      A. D. N., and Coon, M. J. (1997) Biochemistry 36, 4895-4902). Inactivation by
      those aldehydes apparently occurs by homolytic cleavage of a peroxyhemiacetal
      intermediate to yield formate and an alkyl radical that reacts with the heme. In
      sharp contrast, the rate of mechanism-based inactivation by HNE is decreased with
      the T302A mutant relative to that of the wild-type P450 2B4, and mass spectral
      analysis of the heme adduct formed shows that deformylation does not occur. We
      therefore propose that the metabolic activation of HNE involves formation of an
      acyl carbon radical that leads to the carboxylic acid or alternatively reacts
      with the heme.

PMID- 9278418
TI  - Stimulation by 1alpha,25(OH)2-vitamin D3 of whole cell chloride currents in
      osteoblastic ROS 17/2.8 cells. A structure-function study.
AB  - 1alpha,25-Dihydroxyvitamin D3 (1alpha,25(OH)2D3) can generate biological
      responses via genomic and nongenomic mechanisms. This article reports for the
      first time the effects of 1alpha,25(OH)2D3 and structurally related analogs on
      whole cell chloride currents in osteoblastic cells. 1alpha,25(OH)2D3 promoted the
      rapid enhancement of outwardly rectifying Cl- currents in 93% of the osteoblasts
      in a concentration-dependent manner, with a maximal increase of about 4-fold
      between 0.5 and 5 nM. This effect of 1alpha,25(OH)2D3 was blocked by 1 nM
      stereoisomer 1beta,25(OH)2D3 when added to the bath before 1alpha,25(OH)2D3. On
      the other hand, 1 nM of the 6-s-cis locked analog 1alpha,25(OH)2-lumisterol3
      significantly increased by about 2.2-fold outward Cl- currents in the ROS 17/2.8
      cells, whereas the increase promoted by same concentration of the 6-s-trans
      locked analog 1alpha,25(OH)2-tachysterol (0.8-fold) was significantly lower,
      suggesting that the 6-s-cis locked or steroid-like form was preferred over the
      extended 6-s-trans conformer to promote these rapid effects of the hormone. We
      conclude that the agonist effects of 1alpha,25(OH)2D3 in osteoblasts at the
      cellular membrane level seem to be determined by some structural features of the
      molecule which may be crucial for its interaction with a putative membrane
      receptor in the cell surface.

PMID- 9278419
TI  - Taste buds have a cyclic nucleotide-activated channel, CNGgust.
AB  - Cyclic nucleotide-gated (CNG) channels have been characterized as important
      factors involved in physiological processes including sensory reception for
      vision and olfaction. The possibility thus exists that a certain CNG channel
      functions in gustation as well. In the present study, we carried out reverse
      transcription-polymerase chain reaction and genomic DNA cloning and characterized
      a CNG channel (CNGgust) as a cyclic nucleotide-activated species expressed in rat
      tongue epithelial tissues where taste reception takes place. Several types of 5'
      rapid amplification of cDNA ends clones of CNGgust cDNA were obtained with
      various 5'-terminal sequences. As the CNGgust gene was a single copy, the
      formation of such CNGgust variants should result from alternative splicing. The
      encoded protein was homologous to known vertebrate CNG channels with 50-80%
      similarities in amino acid sequence, and particularly homologous to bovine testis
      CNG channel and human cone CNG channel with 82% similarities. CNGgust was
      functional when expressed in human embryonic kidney cells, where it opened upon
      the addition of cGMP or cAMP. Immunohistochemical analysis using an antibody
      raised against a CNGgust peptide demonstrated the channel to be localized on the
      pore side of each taste bud in the circumvallate papillae, with no signal
      observed for degenerated taste buds after denervation of the glossopharyngeal
      nerve. All these results, together with the indication that cyclic nucleotides
      play a role gustatory signaling pathway(s), strongly suggest the involvement of
      CNGgust in taste signal transduction.

PMID- 9278420
TI  - The receptor binding site of human interleukin-3 defined by mutagenesis and
      molecular modeling.
AB  - Interleukin-3 (IL-3) is a member of the cytokine superfamily that promotes multi
      potential hematopoietic cell growth by interacting with a cell surface receptor
      composed of alpha and beta chains. The newly available three-dimensional
      structure of a variant of human (h) IL-3 allowed us to evaluate new and existing
      mutagenesis data and to rationally interpret the structure-function relationship
      of hIL-3 on a structural basis. The amino acid residues that were identified to
      be important for hIL-3 activity are grouped into two classes. The first class
      consists of largely hydrophobic residues required for the structural integrity of
      the protein, including the residues in IL-3 that are largely conserved among 10
      mammalian species. These residues form the core of a scaffold for the second
      class of more rapidly diverging solvent-exposed residues, likely to be required
      for interaction with the receptor. Ten important and solvent-exposed residues,
      Asp21, Gly42, Glu43, Gln45, Asp46, Met49, Arg94, Pro96, Phe113, and Lys116, map
      to one side of the protein and form a putative binding site for the alpha subunit
      of the receptor. A model of the IL-3.IL-3 receptor complex based on the human
      growth hormone (hGH).hGH soluble receptor complex structure suggests that the
      interface between IL-3 and the IL-3 receptor alpha subunit consists of a cluster
      of hydrophobic residues flanked by electrostatic interactions. Although the IL
      3/IL-3 receptor beta subunit interface cannot be uniquely located due to the lack
      of sufficient experimental data, several residues of the beta subunit that may
      interact with Glu22 of IL-3 are proposed. The role of these residues can be
      tested in future mutagenesis studies to define the interaction between IL-3 and
      IL-3 receptor beta subunit.

PMID- 9278421
TI  - Hypoxia-inducible factor 1alpha (HIF-1alpha) protein is rapidly degraded by the
      ubiquitin-proteasome system under normoxic conditions. Its stabilization by
      hypoxia depends on redox-induced changes.
AB  - The hypoxia-inducible factor 1 transcriptional activator complex (HIF-1) is
      involved in the activation of the erythropoietin and several other hypoxia
      responsive genes. The HIF-1 complex is composed of two protein subunits: HIF
      1beta/ARNT (aryl hydrocarbon receptor nuclear translocator), which is
      constitutively expressed, and HIF-1alpha, which is not present in normal cells
      but induced under hypoxic conditions. The HIF-1alpha subunit is continuously
      synthesized and degraded under normoxic conditions, while it accumulates rapidly
      following exposure to low oxygen tensions. The involvement of the ubiquitin
      proteasome system in the proteolytic destruction of HIF-1 in normoxia was studied
      by the use of specific inhibitors of the proteasome system. Lactacystin and MG
      132 were found to protect the degradation of the HIF-1 complex in cells
      transferred from hypoxia to normoxia. The same inhibitors were able to induce HIF
      1 complex formation when added to normoxic cells. Final confirmation of the
      involvement of the ubiquitin-proteasome system in the regulated degradation of
      HIF-1alpha was obtained by the use of ts20TGR cells, which contain a temperature
      sensitive mutant of E1, the ubiquitin-activating enzyme. Exposure of ts20 cells,
      under normoxic conditions, to the non-permissive temperature induced a rapid and
      progressive accumulation of HIF-1. The effect of proteasome inhibitors on the
      normoxic induction of HIF-1 binding activity was mimicked by the thiol reducing
      agent N-(2-mercaptopropionyl)-glycine and by the oxygen radical scavenger 2
      acetamidoacrylic acid. Furthermore, N-(2-mercaptopropionyl)-glycine induced gene
      expression as measured by the stimulation of a HIF-1-luciferase expression vector
      and by the induction of erythropoietin mRNA in normoxic Hep 3B cells. These last
      findings strongly suggest that the hypoxia induced changes in HIF-1alpha
      stability and subsequent gene activation are mediated by redox-induced changes.

PMID- 9278422
TI  - The X-ray structure of the PurR-guanine-purF operator complex reveals the
      contributions of complementary electrostatic surfaces and a water-mediated
      hydrogen bond to corepressor specificity and binding affinity.
AB  - The purine repressor, PurR, is the master regulatory protein of de novo purine
      nucleotide biosynthesis in Escherichia coli. This dimeric transcription factor is
      activated to bind to cognate DNA operator sites by initially binding either of
      its physiologically relevant, high affinity corepressors, hypoxanthine (Kd = 9.3
      microM) or guanine (Kd = 1.5 microM). Here, we report the 2.5-A crystal structure
      of the PurR-guanine-purF operator ternary complex and complete the atomic
      description of 6-oxopurine-induced repression by PurR. As anticipated, the
      structure of the PurR-guanine-purF operator complex is isomorphous to the PurR
      hypoxanthine-purF operator complex, and their protein-DNA and protein-corepressor
      interactions are nearly identical. The former finding confirms the use of an
      identical allosteric DNA-binding mechanism whereby corepressor binding 40 A from
      the DNA-binding domain juxtaposes the hinge regions of each monomer, thus
      favoring the formation and insertion of the critical minor groove-binding hinge
      helices. Strikingly, the higher binding affinity of guanine for PurR and the
      ability of PurR to discriminate against 2-oxopurines do not result from direct
      protein-ligand interactions, but rather from a water-mediated contact with the
      exocyclic N-2 of guanine, which dictates the presence of a donor group on the
      corepressor, and the better electrostatic complementarity of the guanine base and
      the corepressor-binding pocket.

PMID- 9278423
TI  - High density distribution of endoplasmic reticulum proteins and mitochondria at
      specialized Ca2+ release sites in oligodendrocyte processes.
AB  - In oligodendrocyte processes, methacholine-evoked Ca2+ waves propagate via
      regions of specialized Ca2+ release kinetics (wave amplification sites) at which
      the amplitude and rate of rise of local Ca2+ signals are markedly higher than in
      surrounding areas (Simpson, P. B., and Russell, J. T. (1996) J. Biol. Chem. 271,
      33493-33501). In the present study we have examined the effects of other
      phosphoinositide-coupled agonists on Ca2+ in these cells, and the structural
      specializations underlying regenerative wave amplification sites. Both bradykinin
      and norepinephrine evoke Ca2+ waves, which initiate at the same loci and
      propagate through the cell body and multiple processes via identical wave
      amplification sites. Antibodies against type 2 inositol 1,4,5-trisphosphate
      receptors (InsP3R2) and calreticulin identify expression of these proteins in
      oligodendrocyte membranes in Western blots. Immunocytochemistry followed by high
      resolution fluorescence microscopy revealed that both InsP3R2 and calreticulin
      are expressed in high intensity patches along processes. Cross-correlation
      analysis of the profiles of local Ca2+ release kinetics during a Ca2+ wave and
      immunofluorescence for these proteins along cellular processes showed that the
      domains of high endoplasmic reticulum protein expression correspond closely to
      wave amplification sites. Staining cells with the mitochondrial dye,
      MitoTracker(R), showed that mitochondria are only found in intimate association
      with these sites possessing high density endoplasmic reticulum proteins, and they
      remain in the same locations over relatively long periods of time. It appears,
      therefore, that multiple specializations are found at domains of elevated Ca2+
      release in oligodendrocyte processes, including high levels of calreticulin,
      InsP3R2 Ca2+ release channels, and mitochondria.

PMID- 9278424
TI  - Association of calponin with desmin intermediate filaments.
AB  - Our previous immunoelectron microscopy studies of chicken gizzard smooth muscle
      cells showed that in certain areas the distribution of anti-calponin exhibits a
      high degree of overlap with beta-actin, filamin, and in particular, desmin,
      suggesting that in situ a fraction of calponin may be associated with
      intermediate filaments of the cytoskeleton. In this work we further explore this
      idea by studying the interaction between calponin and desmin. We found that at
      physiological salt concentrations, calponin bound only weakly to synthetic desmin
      intermediate filaments. On the other hand, calponin bound strongly to
      nonfilamentous desmin tetramers and was incorporated into intermediate filaments
      when the two proteins were mixed in a buffer containing 6 M urea and dialyzed
      into a buffer containing 0.15 M NaCl. Anti-calponin was found to label a portion
      of intermediate filaments and dense bodies isolated from gizzard tissues. Our
      findings suggest that in chicken gizzard smooth muscle cells, calponin may be an
      integral component of desmin intermediate filaments in the vicinity of dense
      bodies. Since calponin is also known to bind actin, we hypothesize that one of
      the functions of calponin might be to bridge intermediate filaments with actin in
      dense bodies.

PMID- 9278425
TI  - A minimal murine Msx-1 gene promoter. Organization of its cis-regulatory motifs
      and their role in transcriptional activation in cells in culture and in
      transgenic mice.
AB  - To dissect the cis-regulatory elements of the murine Msx-1 promoter, which lacks
      a conventional TATA element, a putative Msx-1 promoter DNA fragment (from -1282
      to +106 base pairs (bp)) or its congeners containing site-specific alterations
      were fused to luciferase reporter and introduced into NIH3T3 and C2C12 cells, and
      the expression of luciferase was assessed in transient expression assays. The
      functional consequences of the sequential 5' deletions of the promotor revealed
      that multiple positive and negative regulatory elements participate in regulating
      transcription of the Msx-1 gene. Surprisingly, however, the optimal expression of
      Msx-1 promoter in either NIH3T3 or C2C12 cells required only 165 bp of the
      upstream sequence to warrant detailed examination of its structure. Therefore,
      the functional consequences of site-specific deletions and point mutations of the
      cis-acting elements of the minimal Msx-1 promoter were systematically examined.
      Concomitantly, potential transcriptional factor(s) interacting with the cis
      acting elements of the minimal promoter were also studied by gel electrophoretic
      mobility shift assays and DNase I footprinting. Combined analyses of the minimal
      promoter by DNase I footprinting, electrophoretic mobility shift assays, and
      super shift assays with specific antibodies revealed that 5'-flanking regions
      from -161 to -154 and from -26 to -13 of the Msx-1 promoter contains an authentic
      E box (proximal E box), capable of binding a protein immunologically related to
      the upstream stimulating factor 1 (USF-1) and a GC-rich sequence motif which can
      bind to Sp1 (proximal Sp1), respectively. Additionally, we observed that the
      promoter activation was seriously hampered if the proximal E box was removed or
      mutated, and the promoter activity was eliminated completely if the proximal Sp1
      site was similarly altered. Absolute dependence of the Msx-1 minimal promoter on
      Sp1 could be demonstrated by transient expression assays in the Sp1-deficient
      Drosophila cell line cotransfected with Msx-1-luciferase and an Sp1 expression
      vector pPacSp1. The transgenic mice embryos containing -165/106-bp Msx-1 promoter
      LacZ DNA in their genomes abundantly expressed beta-galactosidase in maxillae and
      mandibles and in the cellular primordia involved in the formation of the meninges
      and the bones of the skull. Thus, the truncated murine Msx-1 promoter can target
      expression of a heterologous gene in the craniofacial tissues of transgenic
      embryos known for high level of expression of the endogenous Msx-1 gene and found
      to be severely defective in the Msx-1 knock-out mice.

PMID- 9278426
TI  - LOK is a novel mouse STE20-like protein kinase that is expressed predominantly in
      lymphocytes.
AB  - We have identified a new gene, designated lok (lymphocyte-oriented kinase), that
      encodes a 966-amino acid protein kinase whose catalytic domain at the N terminus
      shows homology to that of the STE20 family members involved in mitogen-activated
      protein (MAP) kinase cascades. The non-catalytic domain of LOK does not have any
      similarity to that of other known members of the family. There is a proline-rich
      motif with Src homology region 3 binding potential, followed by a long coiled
      coil structure at the C terminus. LOK is expressed as a 130-kDa protein, which
      was detected predominantly in lymphoid organs such as spleen, thymus, and bone
      marrow, in contrast to other mammalian members of the STE20 family. LOK
      phosphorylated itself as well as substrates such as myelin basic protein and
      histone IIA on serine and threonine residues but not on tyrosine residues,
      establishing LOK as a novel serine/threonine kinase. When coexpressed in COS7
      cells with the known MAP kinase isoforms (ERK, JNK, and p38), LOK activated none
      of them in contrast to PAK- and GCK-related kinases. These results suggest that
      LOK could be involved in a novel signaling pathway in lymphocytes, which is
      distinct from the known MAP kinase cascades.

PMID- 9278427
TI  - Altered Golgi localization of core 2 beta-1,6-N-acetylglucosaminyltransferase
      leads to decreased synthesis of branched O-glycans.
AB  - Mucin type O-glycans with core 2 branches are distinct from nonbranched O
      glycans, and the amount of core 2 branched O-glycans changes dramatically during
      T cell differentiation. This oligosaccharide is synthesized only when core 2 beta
      1, 6-N-acetylglucosaminyltransferase (C2GnT) is present, and the expression of
      this glycosyltransferase is highly regulated. To understand how O-glycan
      synthesis is regulated by the orderly appearance of glycosyltransferases that
      form core 2 branched O-glycans, the subcellular localization of C2GnT was
      determined by using antibodies generated that are specific to C2GnT. The studies
      using confocal light microscopy demonstrated that C2GnT was localized mainly in
      cis to medial-cisternae of the Golgi. We then converted C2GnT to a trans-Golgi
      enzyme by replacing its Golgi retention signal with that of alpha-2,6
      sialyltransferase, which resides in trans-Golgi. Chinese hamster ovary cells
      expressing wild type C2GnT and the chimeric C2GnT were then subjected to
      oligosaccharide analysis. The results obtained clearly indicate that the
      conversion of C2GnT into a trans-Golgi enzyme resulted in a substantial decrease
      of core 2 branched oligosaccharides. These results, taken together, strongly
      suggest that the predominance of core 2 branched oligosaccharides in those cells
      expressing C2GnT is due to the fact that C2GnT is located earlier in the Golgi
      than alpha-2,3-sialyltransferase that competes with C2GnT for the common
      substrate. Furthermore, alteration of Golgi localization renders the chimeric
      C2GnT much less efficient in synthesizing core 2 branched oligosaccharides,
      indicating the critical role of orderly subcellular localization of
      glycosyltransferases.

PMID- 9278428
TI  - Domain structure of Thermus thermophilus UvrB protein. Similarity in domain
      structure to a helicase.
AB  - UvrB protein plays an essential role in the prokaryotic excision repair system.
      UvrB protein shows cryptic ATPase activity, DNA binding, helicase-like activity,
      and incision activity by interacting with UvrA or UvrC proteins. To reveal the
      structure-function relationship of this multifunctional protein, the domain
      structure of Thermus thermophilus UvrB protein (ttUvrB) was studied by limited
      proteolysis and denaturation experiments. Proteolytic profiles indicated that
      ttUvrB consists of four domains: the N domain (residues 2-105), M domain (106
      455), C1 domain (456-590), and C2 domain (591-665). The properties of the
      proteolytic fragments indicated the involvement of the respective domains in the
      functions of the protein as follows: the N and C1 domains are necessary for
      ATPase activity, the C1 domain is indispensable for DNA binding, and the N and/or
      M domains are involved in UvrA binding. The structural stability of the C1 and C2
      domains was higher than that of the N and M domains, which supports the proposed
      domain nature of ttUvrB. Based on these results and the crystal structure of PcrA
      helicase (Subramanya, H. S., Bird, L. E., Brannigan, J. A., and Wigley, D. B.
      (1996) Nature 384, 379-383), the domain organization of ttUvrB was proposed.

PMID- 9278429
TI  - Methyl-directed repair of mismatched small heterologous sequences in cell
      extracts from Escherichia coli.
AB  - The methyl-directed DNA repair efficiency of a set of M13mp18 heteroduplexes
      containing 1-8 or 22 unpaired bases was determined by using an in vitro DNA
      mismatch repair assay. The unpaired bases of each heteroduplex residing at
      overlapping recognition sites of two restriction endonucleases allow independent
      assay of repair on either DNA strand. Our results showed that the repair of small
      nucleotide heterologies in Escherichia coli extracts was very similar to base
      base mismatch repair, being strand-specific and highly biased to the unmethylated
      strand. The in vitro activity was also dependent on products of mutH, mutL, mutS,
      and uvrD loci and was equally efficient on nucleotide insertions and deletions.
      The repair levels of small heterologies were affected by base composition of the
      heterologies. However, the extent of repair of heteroduplexes containing small
      heterologous sequences was found to decrease with an increase in the number of
      unpaired bases. Heteroduplexes containing an extra nucleotide of 22 bases
      provoked very low level of methyl-directed repair.

PMID- 9278430
TI  - Purification and characterization of UDP-N-acetylglucosamine: alpha1,3-D
      mannoside beta1,4-N-acetylglucosaminyltransferase (N
      acetylglucosaminyltransferase-IV) from bovine small intestine.
AB  - A new beta1,4-N-acetylglucosaminyltransferase (GnT) which involves in branch
      formation of Asn-linked complex-type sugar chains has been purified 224,000-fold
      from bovine small intestine. This enzyme requires divalent cations, such as Mn2+,
      and catalyzes the transfer of GlcNAc from UDP-GlcNAc to biantennary
      oligosaccharide and produces triantennary oligosaccharide with the beta1-4-linked
      GlcNAc residue on the Manalpha1-3 arm. The purified enzyme shows a single band of
      Mr 58,000 and behaves as a monomer. The substrate specificity demonstrated that
      the beta1-2-linked GlcNAc residue on the Manalpha1-3 arm (GnT-I product) is
      essential for the enzyme activity. beta1-4-Galactosylaion to this essential beta1
      2-linked GlcNAc residue or N-acetylglucosaminylation to the beta-linked Man
      residue (bisecting GlcNAc, GnT-III product) blocks the enzyme action, while beta1
      6-N-acetylglucosaminylation to the Manalpha1-6 arm (GnT-V product) increases the
      transfer. Based on these findings, we conclude that the purified enzyme is UDP-N
      acetylglucosamine:alpha-3-D-mannoside beta-1,4-N-acetylglucosaminyltransferase IV
      (GnT-IV), that has been a missing link on biosynthesis of complex-type sugar
      chains.

PMID- 9278432
TI  - Transglutaminase-catalyzed cross-linking of osteopontin is inhibited by
      osteocalcin.
AB  - Osteocalcin, the most abundant noncollagenous protein of bone matrix, has been
      demonstrated to inhibit bone growth by gene knockout experiments (Ducy, P.,
      Desbois, C., Boyce, B., Pinero, G., Story, B., Dunstan, C., Smith, E., Bonadio,
      J., Goldstein, S., Gundberg, C., Bradley, A., and Karsenty, G. (1996) Nature 382,
      448-452). Its specific functional mechanism in bone metabolism is, however,
      largely unknown. In this study, we provide evidence that osteocalcin has an
      inhibitory effect on tissue transglutaminase activity, as measured by cross
      linking of osteopontin, another bone matrix protein. Using a set of synthetic
      peptides, we found that the inhibitory activity resided within the first 13 N
      terminal amino acid residues of osteocalcin. An N-terminal peptide also inhibited
      cross-linking of another tissue transglutaminase substrate, beta-casein. The
      inhibitory peptide was shown to have affinity for the substrates of
      transglutaminase rather than for the enzyme. Since the N terminus of osteocalcin
      exhibits homology to the substrate recognition site sequences of two
      transglutaminases, we conclude that the inhibitory effect is most likely due to
      competition with the enzyme for the transglutaminase-binding region of the
      substrates, osteopontin and beta-casein, which prevents access of the enzyme to
      them to perform its function. The interference of osteocalcin with osteopontin
      cross-linking gives osteocalcin a new potential function as the first protein
      inhibitor of tissue transglutaminase. This suggests a specific role and a
      plausible mechanism for it as a modulator of maturation, stabilization, and
      calcification of bone matrix.

PMID- 9278431
TI  - Expression and efficient export of enzymatically active Mycobacterium
      tuberculosis glutamine synthetase in Mycobacterium smegmatis and evidence that
      the information for export is contained within the protein.
AB  - We have investigated the expression and extracellular release of active,
      recombinant Mycobacterium tuberculosis glutamine synthetase (EC 6.3.1.2), an
      enzyme that is a potentially important determinant of M. tuberculosis infection
      and whose extracellular release is correlated with pathogenicity. The M.
      tuberculosis glutamine synthetase gene encodes a polypeptide of 478 amino acids;
      12 such subunits comprise the active enzyme. Northern blot, nuclease S1, and
      primer extension analyses revealed glutamine synthetase specific transcripts of
      approximately 1,550 and 1,650 nucleotides produced under low and high nitrogen
      conditions, respectively. Expression of recombinant M. tuberculosis glutamine
      synthetase in Escherichia coli YMC21E, a glutamine synthetase deletion mutant,
      led to transcomplementation of the mutant but not to release of active enzyme.
      Expression in Mycobacterium smegmatis 1-2c, from the gene's own promoter,
      resulted in the release of >95% of all recombinant enzyme. No hybrid molecules
      containing M. tuberculosis and M. smegmatis glutamine synthetase subunits were
      detected. Native and recombinant exported and intracellular glutamine synthetase
      molecules were indistinguishable from one another by mass, N-terminal amino acid
      sequence, antibody reactivity, and enzymatic activity. Since M. tuberculosis
      glutamine synthetase is similar to other, strictly intracellular, bacterial
      glutamine synthetases and the DNA sequence upstream of the structural gene does
      not encode a leader peptide, the information to target the protein for export
      must be contained in its amino acid sequence and/or conformation.

PMID- 9278433
TI  - Isolation of cDNA encoding guinea pig neutrophil cationic antibacterial
      polypeptide of 11 kDa (CAP11) and evaluation of CAP11 mRNA expression during
      neutrophil maturation.
AB  - Neutrophils contain various antibacterial polypeptides and proteins in the
      granules that contribute to the killing of microorganisms. Recently, we have
      purified a cationic antibacterial polypeptide of 11 kDa (CAP11) from guinea pig
      neutrophil granules. CAP11 is a homodimer of
      G1LRKKFRKTRKRIQKLGRKIGKTGRKVWKAWREYGQIPYPCRI43 joined with one disulfide bond. In
      this study, to understand the regulation of CAP11 expression, we isolated and
      analyzed cDNA encoding CAP11. Furthermore, we investigated the expression of
      CAP11 mRNA during neutrophil maturation and localization of CAP11 among
      neutrophil granule subsets. Sequence analysis of CAP11 cDNA isolated from guinea
      pig bone marrow cells using rapid amplification of cDNA ends technique indicated
      that CAP11 is synthesized as a precursor comprising 178 amino acid residues,
      which is composed of a signal peptide (N-terminal 29 residues), a propeptide (106
      residues), and a C-terminal mature peptide (43 residues). Interestingly, the
      predicted CAP11 precursor displayed the characteristic features of cathelicidins,
      a novel protein family of antibacterial polypeptides with a conserved cathelin
      like pro-region and a variable C-terminal antibacterial domain. Northern blot and
      Western blot analyses using neutrophils, macrophages, eosinophils, mononuclear
      cells, and bone marrow cells revealed that only neutrophils and bone marrow cells
      expressed CAP11 mRNA and contained CAP11, suggesting that expression of CAP11 is
      neutrophil lineage-specific. Furthermore, Northern blot analysis using bone
      marrow cells separated according to their maturation stages showed that CAP11
      mRNA was predominantly expressed in the cells at later stages of neutrophil
      maturation. Consistent with this, in situ hybridization using CAP11-specific cRNA
      probe demonstrated that CAP11 mRNA was primarily expressed at metamyelocyte
      stage. In addition, extracellular release assay revealed that CAP11 was readily
      released from neutrophils accompanied with gelatinase by low concentrations of N
      formyl-Met-Leu-Phe without release of specific and azurophil granule components,
      and CAP11 was found to be exclusively present in the fraction containing
      gelatinase granules, prepared by Percoll density gradient centrifugation.
      Together these observations indicate that CAP11 is a member of cathelicidin
      family and its mRNA is preferentially expressed at the later stage of neutrophil
      maturation (i.e. metamyelocyte stage). Furthermore, CAP11 may be stored in the
      granule subset, possibly the gelatinase granule.

PMID- 9278435
TI  - Carbohydrate structures of recombinant human alpha-L-iduronidase secreted by
      Chinese hamster ovary cells.
AB  - alpha-L-Iduronidase is a lysosomal hydrolase that is deficient in Hurler syndrome
      and clinically milder variants. Recombinant human alpha-L-iduronidase, isolated
      from secretions of an overexpressing Chinese hamster ovary cell line, is
      potentially useful for replacement therapy of these disorders. Because of the
      importance of carbohydrate residues for endocytosis and lysosomal targeting, we
      examined the oligosaccharides of recombinant alpha-L-iduronidase at each of its
      six N-glycosylation sites. Biosynthetic radiolabeling showed that three or four
      of the six oligosaccharides of the secreted enzyme were cleaved by endo-beta-N
      acetylglucosaminidase H, with phosphate present on the sensitive oligosaccharides
      and L-fucose on the resistant ones. For structural analysis, tryptic and
      chymotryptic glycopeptides were isolated by lectin binding and reverse phase high
      pressure liquid chromatography; their molecular mass was determined by matrix
      assisted laser desorption-time of flight mass spectrometry before and after
      treatment with endo- or exoglycosidases or with alkaline phosphatase.
      Identification of the peptides was assisted by amino- or carboxyl-terminal
      sequence analysis. The major oligosaccharide structures found at each site were
      as follows: Asn-110, complex; Asn-190, complex; Asn-336, bisphosphorylated
      (P2Man7GlcNAc2); Asn-372, high mannose (mainly Man9GlcNAc2, some of which was
      monoglucosylated); Asn-415, mixed high mannose and complex; Asn-451,
      bisphosphorylated (P2Man7GlcNAc2). The Asn-451 glycopeptide was unexpectedly
      resistant to digestion by N-glycanase unless first dephosphorylated, but it was
      sensitive to endo-beta-N-acetylglucosaminidase H and to glycopeptidase A. The
      heterogeneity of carbohydrate structures must represent the accessibility of the
      glycosylation sites as well as the processing capability of the overexpressing
      Chinese hamster ovary cells.

PMID- 9278434
TI  - Retinoblastoma protein-dependent growth signal conflict and caspase activity are
      required for protein kinase C-signaled apoptosis of prostate epithelial cells.
AB  - Both protein kinase C and the retinoblastoma tumor suppressor protein have been
      linked to the regulation of cell growth and cell death, suggesting the
      differential roles these factors play in mediating cell fate. In some cells,
      protein kinase C-induced activation of the retinoblastoma protein results in G1
      arrest. However, inducible overexpression and activation of the protein kinase
      Calpha isozyme or the addition of 12-O-tetradecanoylphorbol-13-acetate in the
      prostate epithelial cell line, LNCaP, resulted in apoptosis preceded by induction
      of p21 and dephosphorylation of the retinoblastoma protein. Consistent with a
      role for the retinoblastoma growth suppressor protein in protein kinase C-induced
      apoptosis, DU145 cells, which do not express functional retinoblastoma protein or
      LNCaP cells, which have been transfected with the retinoblastoma inhibitor, E1a,
      were resistant to apoptosis. LNCaP apoptosis was initiated by a unique conflict
      between the growth-suppressive activity of the retinoblastoma protein and growth
      promoting mitogenic signals. Thus, when this conflict was prevented by serum
      depletion, apoptosis was suppressed. The caspase family of cysteine proteases is
      believed to encompass the execution machinery of mammalian apoptosis, and
      addition of the cell-permeable caspase inhibitor, Z-Val-Ala-Asp
      fluoromethylketone, afforded nearly total protection from protein kinase C
      signaled apoptosis. This protection correlated with the total loss of caspase
      activity as measured by the proteolytic cleavage of nuclear poly(ADP-ribose)
      polymerase. On the basis of these results, we propose that protein kinase C
      regulates a novel cell death pathway that is initiated by a cellular conflict
      between retinoblastoma growth-suppressive signals and serum mitogenic signals in
      proliferating prostate epithelial cells and that is executed by the caspase
      family of cysteine proteases.

PMID- 9278436
TI  - The UL8 subunit of the heterotrimeric herpes simplex virus type 1 helicase
      primase is required for the unwinding of single strand DNA-binding protein (ICP8)
      coated DNA substrates.
AB  - The Herpes simplex virus type 1 primosome consists of three subunits that are the
      products of the UL5, UL8, and UL52 genes. The heterotrimeric enzyme has DNA
      dependent ATPase, helicase, and primase activities. Earlier studies show that a
      subassembly consisting of the UL5 and UL52 gene products was indistinguishable
      from the heterotrimeric enzyme in its helicase and primase activities. We
      demonstrate here that the UL8 protein is required for the helicase activity of
      the UL5/52 subassembly on long duplex DNA substrates (>30 nucleotides) with a
      single-stranded DNA loading site fully coated with the virus-encoded single
      strand DNA binding protein, ICP8. The Escherichia coli single strand DNA binding
      protein cannot substitute for ICP8, suggesting a specific physical interaction
      between ICP8 and the UL8 protein. Surface plasmon resonance measurements
      demonstrated an interaction between ICP8 and the UL5/52/8 heterotrimer but not
      with the UL5/52 subassembly or the UL8 protein alone. At a subsaturating level of
      ICP8, the UL5/52 subassembly does show helicase activity, suggesting that the
      subassembly can bind to single-stranded DNA but not to ICP8-coated DNA.

PMID- 9278437
TI  - Activation of the hematopoietic progenitor kinase-1 (HPK1)-dependent, stress
      activated c-Jun N-terminal kinase (JNK) pathway by transforming growth factor
      beta (TGF-beta)-activated kinase (TAK1), a kinase mediator of TGF beta signal
      transduction.
AB  - Transforming growth factor beta (TGF-beta)-activated kinase (TAK1) is known for
      its involvement in TGF-beta signaling and its ability to activate the p38-mitogen
      activated protein kinase (MAPK) pathway. This report shows that TAK1 is also a
      strong activator of c-Jun N-terminal kinase (JNK). Both the wild-type and a
      constitutively active mutant of TAK1 stimulated JNK in transient transfection
      assays. Mitogen-activated protein kinase kinase 4 (MKK4)/stress-activated protein
      kinase/extracellular signal-regulated kinase (SEK1), a dual-specificity kinase
      that phosphorylates and activates JNK, synergized with TAK1 in activating JNK.
      Conversely, a dominant-negative (MKK4/SEK1 mutant inhibited TAK1-induced JNK
      activation. A kinasedefective mutant of TAK1 effectively suppressed hematopoietic
      progenitor kinase-1 (HPK1)-induced JNK activity but had little effect on germinal
      center kinase activation of JNK. There are two additional MAPK kinase kinases,
      MEKK1 and mixed lineage kinase 3 (MLK3), that are also downstream of HPK1 and
      upstream of MKK4/SEK mutant. However, because the dominant-negative mutants of
      MEKK1 and MLK3 did not inhibit TAK1-induced JNK activity, we conclude that
      activation of JNK1 by TAK1 is independent of MEKK1 and MLK3. In addition to TAK1,
      TGF-beta also stimulated JNK activity. Taken together, these results identify
      TAK1 as a regulator in the HPK1 --> TAK1 --> MKK4/SEK1 --> JNK kinase cascade and
      indicate the involvement of JNK in the TGF-beta signaling pathway. Our results
      also suggest the potential roles of TAK1 not only in the TGF-beta pathway but
      also in the other HPK1/JNK1-mediated pathways.

PMID- 9278438
TI  - Glucose catabolism in cancer cells. The type II hexokinase promoter contains
      functionally active response elements for the tumor suppressor p53.
AB  - The p53 tumor suppressor is found to be mutated and abundant in a wide variety of
      tumors. Within tumors showing rapid growth, the Type II isoform of hexokinase is
      also highly expressed to facilitate high rates of glucose catabolism, which in
      turn promote their rapid proliferation. We previously reported isolation of the
      proximal promoter of the Type II hexokinase gene from the highly glycolytic
      hepatoma AS-30D (Mathupala, S. P., Rempel, A., and Pedersen, P. L. (1995) J.
      Biol. Chem. 270, 16918-16925). Here, we show that a p53 protein, exhibiting two
      point mutations in its cDNA, is abundantly expressed in the AS-30D hepatoma. Co
      expression studies showed that p53 overexpression significantly and reproducibly
      activated the Type II hexokinase promoter. Two functional p53 motifs were
      identified within this promoter by footprint and gel retardation analyses.
      Presence of functional p53 response elements on the Type II hexokinase promoter
      and the positive regulatory effect on the promoter by the mutant p53 indicates
      that in rapidly growing liver tumors, and perhaps in many other tumors as well,
      this highly abundant p53 protein plays a role in maintaining a high glycolytic
      rate. This is the first report of a possible link between loss of cell cycle
      control in rapidly growing cancer cells and their high glycolytic phenotype.

PMID- 9278439
TI  - Mammalian alkaline phosphatases are allosteric enzymes.
AB  - Mammalian alkaline phosphatases (APs) are zinc-containing metalloenzymes encoded
      by a multigene family and functional as dimeric molecules. Using human placental
      AP (PLAP) as a paradigm, we have investigated whether the monomers in a given
      PLAP dimer are subject to cooperativity during catalysis following an allosteric
      model or act via a half-of-sites model, in which at any time only one single
      monomer is operative. Wild type and mutant PLAP homodimers and heterodimers were
      produced by stably transfecting Chinese hamster ovary cells with mutagenized PLAP
      cDNAs followed by enzyme extraction, purification, and characterization.
      [Gly429]PLAP manifested negative cooperativity when partially metalated as a
      consequence of the reduced affinity of the incompletely metalated AP monomers for
      the substrate. Upon full metalation with Zn2+, however, the negative
      cooperativity disappeared. To distinguish between an allosteric and a half-of
      sites model, a [Gly429]PLAP-[Ser84]PLAP heterodimer was produced by combining
      monomers displaying high and low sensitivity to the uncompetitive inhibitor L-Leu
      as well as a [Gly429]PLAP-[Ala92]PLAP heterodimer combining a catalytically
      active and inactive monomer, respectively. The L-Leu inhibition profile of the
      [Gly429]PLAP-[Ser84]PLAP heterodimer was intermediate to that for each homodimer
      as predicted by the allosteric model. Likewise, the [Gly429]PLAP-[Ala92]PLAP
      heterodimer was catalytically active, confirming that AP monomers act
      independently of each other. Although heterodimers are structurally asymmetrical,
      they migrate in starch gels with a smaller than expected weighted electrophoretic
      mobility, are more stable to heat denaturation than expected, and are more
      sensitive to L-Leu inhibition than predicted by a strict noncooperative model. We
      conclude that fully metalated mammalian APs are noncooperative allosteric enzymes
      but that the stability and catalytic properties of each monomer are controlled by
      the conformation of the second AP subunit.

PMID- 9278440
TI  - Silencer activity in the interferon-A gene promoters.
AB  - Interferon-A (IFN-A) differential gene expression is modulated by a complex
      interplay between cis-acting DNA elements and the corresponding specific trans
      regulating factors. Substitutions in the proximal virus-responsive element of the
      interferon-A (IFN-A) promoters contribute to their differential gene expression.
      The 5' distal silencing region in the weakly virus-inducible murine IFN-A11 gene
      has been previously delimited. DNase I footprinting experiments and transient
      gene expression assays demonstrate identical silencing activity in equivalent
      regions of the genes for IFN-A11 and IFN-A4 promoters. A minimal 20-mer distal
      negative regulatory element (DNRE) in both promoters is necessary and sufficient
      for the silencing and a region in the highly inducible IFN-A4 promoter located
      between the silencer and the virus-responsive element overrides the silencer
      activity. Mutations in the central region of the DNRE, causing derepression, also
      altered the formation of one of the two major DNA-protein complexes. One of these
      contains a protein related to or identical to the high mobility group I(Y)
      proteins, while the other complex contains a major protein present in uninduced
      and virus-induced cells with a molecular mass of 38 kDa, which may be related to
      the silencer activity. Similar DNREs are present in other virus-uninducible IFN-A
      promoters, and these data suggest that a common silencer may mediate the
      transcriptional repression in different genes of this family.

PMID- 9278441
TI  - A novel cardiac-restricted target for doxorubicin. CARP, a nuclear modulator of
      gene expression in cardiac progenitor cells and cardiomyocytes.
AB  - Doxorubicin (Dox), a cardiotoxic antineoplastic drug, disrupts the cardiac
      specific program of gene expression (Kurabayashi, M., Dutta, S., Jeyaseelan, R.,
      and Kedes, L. (1995) Mol. Cell. Biol. 15, 6386-6397; Jeyaseelan, R., Poizat, C.,
      Wu, H. Y., and Kedes, L. (1997) J. Biol. Chem. 272, 5828-5832). To determine
      whether this drug might interfere with the function of cardiac-specific
      regulatory pathways, we used a differential display strategy to clone from
      neonatal rat cardiomyocyte candidate mRNAs that were rapidly sensitive to Dox. We
      report here the identification of a constitutively expressed, cardiac-restricted,
      nuclear protein whose mRNA level is exquisitely sensitive to Dox. Hence we have
      named this protein cardiac adriamycin-responsive protein (CARP). CARP mRNA is
      present at the earliest stages of cardiac morphogenesis. It was detected by in
      situ hybridization within the cardiogenic plate of 7. 5-day post coitum (p.c.)
      embryos, and in 8.5-day p.c. embryos CARP transcripts are present in uniformly
      high levels in the myocardium. Throughout cardiac development, CARP expression is
      specific for the myocardium; endocardial cushions and valves exhibit only
      background levels of signal. Transcript levels persist but gradually decrease in
      neonatal, 2-week-old, and adult hearts. There were no stages when CARP mRNA could
      not be detected. The pattern and timing of CARP mRNA expression, including
      transient expression in the tongue at 14.5 days p.c., coincides with that of
      Nkx2.5/Csx (a putative homolog of tinman, the Drosophila melanogaster gene
      responsible for cardiac development). The cloned full-length 1749 nucleotide CARP
      cDNA encodes a 319-amino acid 40-kDa polypeptide containing five tandem ankyrin
      repeats. CARP appears to be the rat homolog of a previously reported human single
      copy gene (C-193; Chu, W., Burns, D. K., Swerlick, R. A., and Presky, D. H.
      (1995) J. Biol. Chem. 270, 10236-10245), whose mRNA is inducible by cytokines
      only in human endothelial cells. CARP appears to function as a negative regulator
      of cardiac-specific gene expression. Overexpression of CARP in cardiomyocytes
      suppresses cardiac troponin C and atrial natriuretic factor transcription.
      Cotransfection experiments in HeLa cells indicate that CARP inhibits Nkx2.5
      transactivation of atrial natriuretic factor promoter. When fused to a GAL4 DNA
      binding domain, CARP has transcriptional inhibitory properties in noncardiac
      cells. CARP thus represents the first example of a cardiac-restricted
      transcriptional regulatory protein that is sensitive to Dox.

PMID- 9278442
TI  - Human lysyl-tRNA synthetase accepts nucleotide 73 variants and rescues
      Escherichia coli double-defective mutant.
AB  - The nucleotide 73 (N73) "discriminator" base in the acceptor stem is a key
      element for efficient and specific aminoacylation of tRNAs and of microhelix
      substrates derived from tRNA acceptor stems. This nucleotide was possibly one of
      the first to be used for differentiating among groups of early RNA substrates by
      tRNA synthetases. In contrast to many other synthetases, we report here that the
      class II human lysyl-tRNA synthetase is relatively insensitive to the nature of
      N73. We cloned, sequenced, and expressed the enzyme, which is a close homologue
      of the class II yeast aspartyl-tRNA synthetase whose co-crystal structure (with
      tRNAAsp) is known. The latter enzyme has a strong requirement for G73, which
      interacts with 4 of the 14 residues within the "motif 2" loop of the enzyme. Even
      though eukaryotic lysine tRNAs also encode G73, the motif 2 loop sequence of
      lysyl-tRNA synthetase differs at multiple positions from that of the aspartate
      enzyme. Indeed, the recombinant human lysine enzyme shows little preference for
      G, and even charges human tRNA transcripts encoding the A73 found in E. coli
      lysine tRNAs. Moreover, while the lysine enzyme is the only one in E. coli to be
      encoded by two separate genes, a double mutant that disables both genes is
      complemented by a cDNA expressing the human protein. Thus, the sequence of the
      loop of motif 2 of human lysyl-tRNA synthetase specifies a structural variation
      that accommodates nucleotide degeneracy at position 73. This sequence might be
      used as a starting point for obtaining highly specific interactions with any
      given N73 by simple amino acid replacements.

PMID- 9278443
TI  - Microfibril-associated glycoprotein-1 (MAGP-1) binds to the pepsin-resistant
      domain of the alpha3(VI) chain of type VI collagen.
AB  - The interactions of type VI collagen have been investigated, using solid phase
      binding assays, with two components of the fibrillin-containing microfibrils, the
      elastin-binding protein, MAGP-1 and its structural relative MAGP-2. Both native
      and pepsin-treated forms of type VI collagen specifically bound to MAGP-1 but not
      to MAGP-2. Pepsin type VI collagen was shown to block the binding of MAGP-1 to
      native type VI collagen indicating that the major MAGP-1-binding site was in the
      triple-helical region of the molecule. MAGP-1 was found not to bind to collagens
      I, III, and V. Affinity blotting of pepsin-treated type VI collagen showed that
      MAGP-1 binding was specific for the collagenous domain of the alpha3(VI) chain.
      Decorin and biglycan were found not to inhibit the interaction of pepsin-treated
      type VI collagen with MAGP-1, indicating that its binding site on the collagen is
      not close to that for the proteoglycans. Reduction and alkylation of disulfide
      bonds in MAGP-1 did not destroy its type VI collagen-binding properties,
      indicating that the binding site was likely to be in the cysteine-free, N
      terminal domain of MAGP-1. Interestingly, the interaction of MAGP-1 with type VI
      collagen was inhibited by tropoelastin, suggesting that the binding sites for
      tropoelastin and type VI collagen may be in the same domain of MAGP-1. A peptide,
      corresponding to amino acids 29-38 of MAGP-1, was found to inhibit the
      interactions of MAGP-1 with type VI collagen and tropoelastin. The results
      suggest that the peptide may contain the binding sequences for both type VI
      collagen and tropoelastin, and thus that these two proteins may share the same
      binding site on MAGP-1. The interactions of MAGP-1 with type VI collagen and
      tropoelastin were both determined to be of moderately high affinity, with Kd
      values of 5.6 x 10(-7) M and 2.6 x 10(-7) M, respectively. The findings indicate
      that MAGP-1 may mediate a molecular interaction between type VI collagen
      microfibrils and fibrillin-containing microfibrils, structures which are often
      found in close proximity to each other in a wide range of extracellular matrices.

PMID- 9278444
TI  - Tyrosine phosphorylation of connexin 43 by v-Src is mediated by SH2 and SH3
      domain interactions.
AB  - Reduction of gap junctional communication in v-src transformed cells is
      accompanied by tyrosine phosphorylation of the gap junction protein, connexin 43
      (Cx43). Cx43 is phosphorylated on tyrosine by v-Src. The Src homology 3 (SH3) and
      Src homology 2 (SH2) domains of v-Src mediate interactions with substrate
      proteins. SH3 domains interact with proline-rich peptide motifs. SH2 domains
      associate with short amino acid sequences containing phosphotyrosine. We present
      evidence that the SH3 and SH2 domains of v-Src bind to proline-rich motifs and a
      phosphorylated tyrosine residue in the C-terminal tail of Cx43. Cx43 bound to the
      SH3 domain of v-Src, but not c-Src, in vitro. Tyrosine-phosphorylated Cx43 bound
      to the SH2 domain of v-Src in vitro. v-Src coprecipitated with Cx43 from v-src
      transformed Rat-1 fibroblasts. Mutations in the SH3 and SH2 domains of v-Src, and
      in the proline-rich region or tyrosine 265 of Cx43, reduced interactions between
      v-Src and Cx43 in vivo. Tyrosine phosphorylation of Cx43 was dependent on the
      association of v-Src and Cx43. These results provide further evidence for the
      direct involvement of v-Src in tyrosine phosphorylation of Cx43 and inhibition of
      gap junctional communication in v-src-transformed cells.

PMID- 9278445
TI  - Substrate specificity of the RNase activity of yeast RNA polymerase III.
AB  - Using yeast RNA polymerase III ternary complexes stalled at various positions on
      the template, we have analyzed the cleavage products that are retained and
      released by the transcription complexes. The retained 5' products result from
      cleavage at uridine residues during retraction, whereas the yield of
      mononucleotides and dinucleotides released indicates that multiple cuts occur
      near the 3' end. Comparison of the cleavage patterns of uridine-containing and 5
      bromouridine-containing transcripts suggests that RNA within an RNA-DNA hybrid
      duplex is the substrate for the 3'-5' exonuclease. During transcription of the
      SUP4 tRNATyr gene, RNA polymerase III produces not only full-length pre-tRNATyr
      but also short oligonucleotides, indicating that exonuclease digestion and
      transcription are concurrent processes. To explore the possibility that these
      oligonucleotides are released by the action of the RNA polymerase III nuclease at
      previously observed uridine-rich pause sites, we tested modified templates
      lacking the arrest sites present in the SUP4 tRNATyr gene. Comparative studies of
      cleavage during transcription for these templates show a direct correlation
      between the number of natural pause sites and the yield of 3' products made. At
      the natural arrest sites and the terminator, RNA polymerase III carries out
      multiple cleavage resynthesis steps, producing short oligoribonucleotides with
      uridine residues at the 3' terminus.

PMID- 9278446
TI  - The mammalian gene of acetylcholinesterase-associated collagen.
AB  - The collagen-tailed or asymmetric forms (A) represent a major component of
      acetylcholinesterase (AChE) in the neuromuscular junction of higher vertebrates.
      They are hetero-oligomeric molecules, in which tetramers of catalytic subunits of
      type T (AChET) are attached to the subunits of a triple-stranded collagen "tail."
      We report the cloning of a rat AChE-associated collagen subunit, Q. We show that
      collagen tails are encoded by a single gene, COLQ. The ColQ subunits form
      homotrimers and readily form collagen-tailed AChE, when coexpressed with rat
      AChET. We found that the same ColQ subunits are incorporated, in vivo, in
      asymmetric forms of both AChE and butyrylcholinesterase. A splice variant from
      the COLQ gene encodes a proline- rich AChE attachment domain without the collagen
      domain but does not represent the membrane anchor of the brain tetramer. The COLQ
      gene is expressed in cholinergic tissues, brain, muscle, and heart, and also in
      noncholinergic tissues such as lung and testis.

PMID- 9278447
TI  - Identification of CFDD (common regulatory factor for DNA replication and DREF
      genes) and role of its binding site in regulation of the proliferating cell
      nuclear antigen gene promoter.
AB  - The Drosophila proliferating cell nuclear antigen (PCNA) gene promoter contains
      at least three transcriptional regulatory elements, the URE (upstream regulatory
      element), DRE (DNA replication-related element), and E2F recognition sites. In
      nuclear extracts of Drosophila Kc cells, we detected a novel protein factor(s),
      CFDD (common regulatory factor for DNA replication and DREF genes) that appeared
      to recognize two unique nucleotide sequences (5'-CGATA and 5'-CAATCA) and bind to
      three sites in the PCNA gene promoter. These sites were located at positions -84
      to -77 (site 1), -100 to -93 (site 2) and -134 to -127 (site 3) with respect to
      the transcription initiation sites. Sites 2 and 3 overlapped with DRE and URE,
      respectively, and the 5'-CGATA matched with the reported recognition sequence of
      BEAF-32 (boundary element-associated factor of 32 kDa). Detailed analyses of CFDD
      recognition sequences and experiments with specific antibodies to DREF (DRE
      binding factor) and BEAF-32 suggest that CFDD is different from DREF, UREF (URE
      binding factor) and BEAF-32. A UV cross-linking experiment revealed that
      polypeptides of approximately 76 kDa in the nuclear extract interact directly
      with the CFDD site 1 sequence. Transient expression assays of chloramphenicol
      acetyltransferase (CAT) in Kc cells transfected with PCNA promoter-CAT fusion
      genes carrying mutations in CFDD site 1 and examination of lacZ expression from
      PCNA promoter-lacZ fusion genes carrying mutations in site 1, introduced into
      flies by germ line transformation, revealed that CFDD site 1 plays an important
      role for the promoter activity both in cultured cells and in living flies. In
      addition to the PCNA gene, multiple CFDD sites were found in promoters of the DNA
      polymerase alpha and DREF genes, and CFDD binding to the DREF promoter was
      confirmed. Therefore, CFDD may play important roles in regulation of Drosophila
      DNA replication-related genes.

PMID- 9278448
TI  - The zinc binuclear cluster activator AlcR is able to bind to single sites but
      requires multiple repeated sites for synergistic activation of the alcA gene in
      Aspergillus nidulans.
AB  - The alcA gene which is part of the recently identified ethanol regulon, is one of
      the most strongly inducible genes in Aspergillus nidulans. Its transcriptional
      activation is mediated by the AlcR transactivator which contains a DNA-binding
      domain belonging to the C6 zinc binuclear cluster family. AlcR differs from the
      other members of this family by several features, the most striking
      characteristic being its binding to both symmetric and asymmetric DNA sites with
      the same apparent affinity. However, AlcR is also able to bind to a single site
      with high affinity, suggesting that unlike the other C6 proteins, AlcR binds as a
      monomer. In this report, we show that AlcR targets, to be functional in vivo,
      have to be organized as inverted or direct repeats. In addition, we show a strong
      synergistic activation of alcA transcription in which the number and the position
      of the AlcR-binding sites are crucial. The fact that the AlcR unit for in vitro
      binding is a single site whereas the in vivo functional unit is a repeat opens
      the question of the mechanism of the strong alcA transactivation. These results
      show that AlcR displays both in vitro and in vivo a new range of binding
      specificity and provides a novel example in the C6 zinc cluster protein family.

PMID- 9278449
TI  - Characterization of the bovine tenascin-X.
AB  - The primary structure of flexilin, an extracellular matrix glycoprotein
      previously identified in bovine tissues (Lethias, C., Descollonges, Y.,
      Boutillon, M.-M., and Garrone, R. (1996) Matrix Biol. 15, 11-19) was determined
      by cDNA cloning. The deduced amino acid sequence (4135 residues) reveals that
      this protein is composed of a succession of peptide motifs characteristic of the
      tenascin family: an amino-terminal domain containing cysteine residues and
      heptads of hydrophobic amino acids, 18.5 epidermal growth factor-like repeats, 30
      fibronectin type III-like (FNIII) domains, and a carboxyl-terminal fibrinogen
      like motif. Sequence analysis indicated that this protein is the bovine
      orthologue of human tenascin-X. By rotary shadowing, bovine tenascin-X was
      identified as monomers with a flexible aspect, which are ended by a globule. More
      FNIII motifs were characterized in the bovine protein than in human tenascin-X.
      The main difference between the human and bovine tenascin-X is found in the
      arrangement of the three classes of highly similar FNIII repeat types in the
      central region of tenascin-X. The bovine FNIII motif b10 exhibits an RGD putative
      cell attachment site. The functional role of this sequence is corroborated by
      cell adhesion on purified tenascin-X, which is inhibited by RGD peptides.
      Moreover, we demonstrate that this RGD site is conserved at the same location in
      the human molecule.

PMID- 9278450
TI  - Characterization of rat liver-specific methionine adenosyltransferase gene
      promoter. Role of distal upstream cis-acting elements in the regulation of the
      transcriptional activity.
AB  - Methionine adenosyltransferase is a ubiquitous enzyme that catalyzes the only
      known route of biosynthesis of S-adenosylmethionine, the major methyl group donor
      in cell metabolism. In mammals, two different methionine adenosyltransferases
      exist: one is confined to the liver, and the other one is distributed in
      extrahepatic tissues. In the present study, we report the cloning of the 5'
      flanking region of liver-specific methionine adenosyltransferase gene from rat.
      Two closely spaced sites for transcriptional initiation were identified by primer
      extension analysis. The major transcription start site was determined to be 29
      nucleotides downstream from the putative TATA box. Transient transfection assays
      of constructs containing sequentially deleted 5'-flanking sequences fused to the
      luciferase gene showed that rat hepatic methionine adenosyltransferase promoter
      was able to efficiently drive reporter expression not only in liver-type cells
      (rat hepatoma H35 cells and human hepatoblastoma HepG2 cells) but also in Chinese
      hamster ovary cells. Two regions spanning nucleotides -1251 to -958 and -197 to
      +65 were found to be crucial for the promoter efficiency. The distal upstream
      region contains elements that positively regulate promoter activity in H35 and
      HepG2 cells but are ineffective in Chinese hamster ovary cells. Eight protein
      binding sites were characterized in both regions by DNase I footprinting
      analysis. Two of these elements, sites A and B, located in the distal region,
      were found to be essential for the regulation of promoter activity.
      Electrophoretic mobility shift assays and competition experiments showed that
      site A is recognized by an NF1 protein. Site B was able to interact with a member
      of HNF-3 family when nuclear extracts from rat liver and H35 cells were used in
      the in vitro assay, but an additional binding activity to an NHF1-like protein
      was obtained with the hepatoma cell extracts. It is suggested that this
      differential binding can contribute to the cell specificity of promoter function.

PMID- 9278451
TI  - Insulin signal transduction by a mutant human insulin receptor lacking the NPEY
      sequence. Evidence for an alternate mitogenic signaling pathway that is
      independent of Shc phosphorylation.
AB  - The cytoplasmic juxtamembrane domain of the human insulin receptor (hIR) contains
      a single copy of the tetrameric amino acid sequence Asn-Pro-Glu-Tyr (NPEY)
      (residues 969-972 in the exon 11-containing B-isoform), which exists in the
      context of NPXY. In this study, we examined the role of NPEY972 in mediating
      insulin signal transduction and cellular biological effects. Transfected Chinese
      hamster ovary cell lines expressing either the wild-type hIR-B isoform (hIR.WT)
      or a mutant receptor lacking the NPEY972 sequence (hIRDeltaNPEY) and control
      Chinese hamster ovary.Neo cells were used to comparatively analyze the following
      insulin effects: in vivo receptor tyrosine autophosphorylation and kinase
      activity, signal transduction to downstream signaling molecules, and stimulation
      of glycogen and DNA synthesis. The results showed that in comparison to hIR.WT,
      the hIRDeltaNPEY mutant demonstrated the following: (a) normal insulin-mediated
      receptor tyrosine phosphorylation, but approximately 50% reduction in
      phosphorylation of p185-(insulin receptor substrate-1) and binding of the p85
      subunit of phosphatidylinositol 3-kinase (PI 3-kinase), (b) an enhanced
      stimulation of PI 3-kinase enzymatic activity, (c) a complete inability to
      phosphorylate Shc, (d) minimal impairment of insulin sensitivity for glycogen
      synthesis, and (e) an augmented response to insulin-stimulated DNA synthesis via
      a high capacity, low sensitivity pathway. These results demonstrate the
      following: 1) the NPEY972 sequence is important but not absolutely essential for
      coupling of hIR kinase to insulin receptor substrate-1 and p85 or for mediating
      insulin's metabolic and mitogenic effects, 2) the NPEY972 sequence is necessary
      for Shc phosphorylation, and 3) the absence of Shc phosphorylation releases the
      constraints on maximal insulin-stimulated mitogenic response, thus indicating
      that alternate signaling pathway(s) exist for this insulin action. This alternate
      pathway appears to be associated with enhanced activation of PI 3-kinase and is
      of high capacity and low sensitivity.

PMID- 9278452
TI  - Efficient assembly of functional cytochrome P450 2C2 requires a spacer sequence
      between the N-terminal signal anchor and catalytic domains.
AB  - Cytochromes P450 (P450) are anchored to the endoplasmic reticulum membrane by an
      N-terminal transmembrane sequence with the catalytic domain facing the
      cytoplasmic side. Within the peptide sequence linking these two domains in P450
      2C2 is a glycine-rich region from residues 22 to 28. To examine the role of this
      region, deletion and substitution mutations were constructed, and the activities
      and spectral properties were determined for the mutant proteins expressed in COS
      1 cells, insect cells, and bacteria. Deletion of residues 22 to 28 or
      substitution of 7 valines for this region inactivated the proteins in COS-1
      cells, and no P450 species was detected for these mutations in bacteria or insect
      cells. Substitution of the three glycine residues with alanine or proline or the
      entire sequence from 22 to 28 with 7 alanines did not reduce lauric acid
      hydroxylase activity of the proteins expressed in COS-1 cells. Reducing the
      number of alanines substituted to 4, 3, and 2 progressively decreased activity in
      COS-1 cells to undetectable levels when 2 alanines were substituted. The loss of
      activity in COS-1 cells correlated with decreased expression of hemoprotein with
      a reduced difference spectrum of 450 nm (P450 species) and a corresponding
      increase in the inactive P420 species in insect cells and bacteria. The
      activities expressed per nanomole of P450 in insect microsomes were similar for
      P450 2C2 and the alanine substitution mutants, including the mutant with 2
      alanines which was inactive in COS-1 cells. The rates of conversion of P450 to
      P420 resulting from incubation at 48 degrees C in vitro were not changed
      sufficiently to explain the increase in expressed P420 observed for the mutants
      with 3 or 7 alanines substituted. These data are consistent with a role for the
      residue 22-28 region as a linker that facilitates the folding of P450; however,
      once the protein is properly folded into the functional P450 species, this region
      has little influence on the stability and activity of the enzyme.

PMID- 9278453
TI  - Platelet-activating factor (PAF) induces growth stimulation, inhibition, and
      suppression of oncogenic transformation in NRK cells overexpressing the PAF
      receptor.
AB  - Platelet-activating factor (PAF) is a phospholipid mediator with various
      physiological functions, including cellular growth and transformation. PAF exerts
      biological activities through G-protein-coupled receptors. In normal rat
      fibroblasts overexpressing a cloned PAF receptor, PAF induced immediate early
      oncogene expression and mitogenic responses. On the other hand, PAF strongly
      inhibited the epidermal growth factor-induced mitogenic growth response, growth
      acceleration, and anchorage-independent cell growth in a soft agar. Furthermore,
      PAF suppressed v-src- or v-ras-induced oncogenic morphological changes and
      anchorage-independent growth. Our observations suggest that PAF is a unique
      growth regulator with apparently diverse functions. Dual actions of PAF may
      relate to the point of action in the cell cycle; PAF stimulates the mitogenic
      response in G0-arrested cells in a pertussis toxin-sensitive manner, while it
      inhibits the G1 to S transition through a pertussis toxin-resistant manner.

PMID- 9278454
TI  - Glomerular mesangial cell-specific transactivation of matrix metalloproteinase 2
      transcription is mediated by YB-1.
AB  - Mesangial cell (MC) activation plays a pivotal role in the development of the end
      stage sclerotic lesion characteristic of most forms of chronic glomerular
      disease. We have previously demonstrated that MC activation is directly linked to
      high level expression of the matrix metalloproteinase-2 (MMP-2) enzyme (Turck,
      J., Pollock, A. S., Lee, L., Marti, H.-P., and Lovett, D. H. (1996) J. Biol.
      Chem. 25, 15074-15083), the transcription of which is regulated in a tissue
      specific fashion. Recent studies (Harendza, S., Pollock, A., Mertens, P. R., and
      Lovett, D. H. (1995) J. Biol. Chem. 270, 18786-18796) delineated a strong cis
      acting enhancer element, designated MMP-2 RE1, within the 5'-flanking region of
      the rat MMP-2 gene. Gel shift, DNA footprint, and transcriptional analyses mapped
      the enhancer element to a unique 40-base pair (bp) sequence located at -1322 to 
      1282 bp relative to the translational start site. Bromodeoxyuridine-substituted
      UV cross-linking of the 40-bp enhancer element with MC nuclear extracts yielded a
      single protein of 52 kDa, while Southwestern blot analysis with MMP-2 RE1
      demonstrated three hybridizing nuclear proteins of 52, 62, and 86 kDa size.
      Screening of a human MC cDNA expression library with MMP-2 RE1 exclusively
      yielded clones with the identical sequence of the transcription factor YB-1.
      Western blot and supershift gel analysis of MC nuclear extracts with an anti-YB-1
      antibody confirmed the presence of YB-1 within the shifted complex. Examination
      of the MMP-2 RE1 sequence revealed an incomplete Y-box sequence (CTGCTGGGCAAG),
      which specifically interacted with recombinant YB-1 on DMS protection
      footprinting analysis. YB-1 protein preferentially bound the single-stranded
      components of the 40-bp MMP-2 RE1 and, with increasing concentrations, formed
      multimeric complexes. Co-transfection of YB-1 in MC increased the enhancer
      activity within the context of the native MMP-2 promoter, while transfection of
      non-MMP-2-synthesizing glomerular epithelial cells with YB-1 led to
      transcriptional suppression. This study indicates that YB-1 is a major, cell type
      specific transactivator of MMP-2 transcription by glomerular mesangial cells.

PMID- 9278455
TI  - Regulation of inosine-5'-monophosphate dehydrogenase type II gene expression in
      human T cells. Role for a novel 5' palindromic octamer sequence.
AB  - Expression of the gene encoding human inosine- 5'-monophosphate dehydrogenase
      (IMPDH) type II, an enzyme catalyzing the rate-limiting step in the generation of
      guanine nucleotides, is increased more than 10-fold in activated peripheral blood
      T lymphocytes and is required for T cell activation. We have examined the 5'
      regulatory sequences that are important for the transcriptional regulation of
      this gene in T cells. DNase I mapping of genomic DNA identified a hypersensitive
      element near the transcription initiation site. Fine mapping by in vivo
      footprinting demonstrated five transcription factor binding sites that are
      occupied in both resting and activated peripheral blood T lymphocytes; these are
      tandem CRE motifs, a Sp1 site, an overlapping Egr-1/Sp1 site, and a novel
      palindromic octamer sequence (POS). The tandem CRE and POS sites are of major
      functional importance as judged by mutational and electrophoretic mobility shift
      analyses. These data provide evidence that expression of the human IMPDH type II
      gene is predominantly regulated by the nuclear factors ATF-2 and an as yet
      unidentified POS-binding protein. Additional major protein-DNA interactions do
      not occur within the promoter region after T lymphocyte activation, indicating a
      requirement for additional protein-protein interactions and/or post-translational
      modifications of pre-bound transcription factors to account for the observed
      increase in IMPDH type II gene expression.

PMID- 9278457
TI  - Identification and characterization of a novel microsomal enzyme with glutathione
      dependent transferase and peroxidase activities.
AB  - 5-Lipoxygenase activating protein (FLAP), leukotriene-C4 (LTC4) synthase, and
      microsomal glutathione S-transferase II (microsomal GST-II) are all members of a
      common gene family that may also include microsomal GST-I. The present work
      describes the identification and characterization of a novel member of this
      family termed microsomal glutathione S-transferase III (microsomal GST-III). The
      open reading frame encodes a 16.5-kDa protein with a calculated pI of 10.2.
      Microsomal GST-III has 36, 27, 22, and 20% amino acid identity to microsomal GST
      II, LTC4 synthase, microsomal GST-I, and FLAP, respectively. Microsomal GST-III
      also has a similar hydrophobicity pattern to FLAP, LTC4 synthase, and microsomal
      GST-I. Fluorescent in situ hybridization mapped microsomal GST-III to chromosomal
      localization 1q23. Like microsomal GST-II, microsomal GST-III has a wide tissue
      distribution (at the mRNA level) and is predominantly expressed in human heart,
      skeletal muscle, and adrenal cortex, and it is also found in brain, placenta,
      liver, and kidney tissues. Expression of microsomal GST-III mRNA was also
      detected in several glandular tissues such as pancreas, thyroid, testis, and
      ovary. In contrast, microsomal GST-III mRNA expression was very low (if any) in
      lung, thymus, and peripheral blood leukocytes. Microsomal GST-III protein was
      expressed in a baculovirus insect cell system, and microsomes from Sf9 cells
      containing either microsomal GST-II or microsomal GST-III were both found to
      possess glutathione-dependent peroxidase activity as shown by their ability to
      reduce 5-HPETE to 5-HETE in the presence of reduced glutathione. The apparent Km
      of 5-HPETE was determined to be approximately 7 microM for microsomal GST-II and
      21 microM for microsomal GST-III. Microsomal GST-III was also found to catalyze
      the production of LTC4 from LTA4 and reduced glutathione. Based on these
      catalytic activities it is proposed that this novel membrane protein is a member
      of the microsomal glutathione S-transferase super family, which also includes
      microsomal GST-I, LTC4 synthase, FLAP, and microsomal GST-II.

PMID- 9278456
TI  - Kringle 5 of plasminogen is a novel inhibitor of endothelial cell growth.
AB  - Angiostatin is a potent angiogenesis inhibitor which has been identified as an
      internal fragment of plasminogen that includes its first four kringle modules. We
      have recently demonstrated that the anti-endothelial cell proliferative activity
      of angiostatin is also displayed by the first three kringle structures of
      plasminogen and marginally so by kringle 4 (Cao, Y., Ji, R.-W., Davidson, D.,
      Schaller, J., Marti, D., Sohndel, S., McCance, S. G., O'Reilly, M. S. , Llinas,
      M., and Folkman, J. (1996) J. Biol. Chem. 271, 29461-29467). We now report that
      the kringle 5 fragment of human plasminogen is a specific inhibitor for
      endothelial cell proliferation. Kringle 5 obtained as a proteolytic fragment of
      human plasminogen displays potent inhibitory effect on bovine capillary
      endothelial cells with a half-maximal concentration (ED50) of approximately 50
      nM. Thus, kringle 5 would appear to be more potent than angiostatin on inhibition
      of basic fibroblast growth factor-stimulated capillary endothelial cell
      proliferation. Appropriately folded recombinant mouse kringle 5 protein,
      expressed in Escherichia coli, exhibits a comparable inhibitory effect as the
      proteolytic kringle 5 fragment. Thus, kringle 5 domain of human plasminogen is a
      novel endothelial inhibitor that is sufficiently potent to block the growth
      factor-stimulated endothelial cell growth.

PMID- 9278458
TI  - An interleukin (IL)-13 receptor lacking the cytoplasmic domain fails to transduce
      IL-13-induced signals and inhibits responses to IL-4.
AB  - Interleukin (IL)-13 is a pleiotropic immunoregulatory cytokine that shares many,
      although not all, of the biological activities of IL-4. The overlapping
      biological properties of IL-4 and IL-13 appear to be due to the existence of
      shared components of the receptors, and we and others showed that the IL-4
      receptor-alpha is involved in signal transduction paths activated by both. We
      show here that expression of the IL-13 receptor-alpha in two factor-dependent
      cell lines, the premyeloid FD5 and the T lymphoid CT4.S, conferred the ability to
      grow continuously in response to IL-13; to respond to IL-13 with tyrosine
      phosphorylation of JAK1, Tyk2, IL-4Ralpha, IRS-2, and STAT6; and to respond to IL
      4 with tyrosine phosphorylation of Tyk2 in addition to those induced in parental
      cell lines. Expression of a truncated IL-13 receptor-alpha that lacked the
      cytoplasmic domain demonstrated that this domain was essential for IL-13
      dependent growth and phosphorylation of the above substrates. Expression of this
      truncated IL-13 receptor also resulted in an inhibition of biochemical and
      biological responses to IL-4 that was exacerbated by the presence of IL-13. These
      dominant inhibitory effects indicate that the extracellular domain of the
      truncated IL-13 receptor competes with gammac for complexes of IL-4 and the IL-4
      receptor-alpha, or, when itself bound to IL-13, competes with IL-4 for the IL-4
      receptor-alpha.

PMID- 9278459
TI  - Specific binding of acidic phospholipids to microtubule-associated protein MAP1B
      regulates its interaction with tubulin.
AB  - Microtubule-associated protein MAP1B, a major neuronal cytoskeletal protein, is
      expressed highly during the early stage of brain development and is thought to
      play an important role in brain development. Although it has been shown that
      MAP1B localizes both in cytosol and particulate fractions, the underlying
      molecular mechanism in the membrane localization has yet to be elucidated. In the
      present study, we show that MAP1B purified from young rat brain can bind to
      acidic phospholipids, such as phosphatidylserine, but not to a neutral
      phospholipid, phosphatidylcholine. Furthermore, the binding of MAP1B to taxol
      stabilized microtubules was inhibited by the addition of phosphatidylserine or
      phosphatidylinositol. The addition of phosphatidylcholine showed no effect on the
      binding of MAP1B to the microtubules. A 120-kDa microtubule-binding fragment of
      MAP1B was also released from microtubules by the addition of acidic
      phospholipids. Synthetic peptides derived from the C-terminal half of the tubulin
      binding domain, but not that corresponding to the N-terminal half, bound to
      acidic phospholipids specifically. These results suggest that MAP1B binds to
      biological membranes through its tubulin-binding site, and the binding may play a
      regulatory role in MAP1B-microtubule interaction.

PMID- 9278460
TI  - p107 and p130 associated cyclin A has altered substrate specificity.
AB  - We demonstrate that p107 and p130 immune complexes exhibit kinase activity. We
      have tested such immune complexes with four substrates commonly utilized to assay
      Cdk activity, including all three known members of the retinoblastoma family.
      Immunodepletion revealed this kinase activity could be abolished by removal of
      either cyclin A or Cdk2 but was unaffected by removal of Cdk4 or any D-type
      cyclin. The appearance of p107 associated activity followed the accumulation of
      p107 protein. In contrast, the kinase activity associated with p130 immune
      complexes became apparent after mid-G1, coincident with p130
      hyperphosphorylation. GST-Rb, GST-p107, and GST-p130 (where GST indicates
      glutathione S-transferase) were equally suitable substrates in p107 and p130
      immune complex kinase assays, yielding activity equal to 25% of the cyclin A
      activity present. The p107 and p130 associated activity was unable to
      phosphorylate histone H1, suggesting the p107 and p130 associated cyclin A/Cdk2
      may represent a distinct pool with a distinct substrate specificity. The p107 and
      p130 associated activity was released from the immune complexes upon incubation
      with ATP and Mg2+ and exhibited the same substrate preference observed with the
      untreated immune complex. Our data suggest that p107 and p130 recognize, or form
      by association, a distinct pool of cyclin A/Cdk2 that preferentially
      phosphorylates retinoblastoma family members.

PMID- 9278461
TI  - Proteolytic cleavage of the mdm2 oncoprotein during apoptosis.
AB  - The mdm2 oncogene encodes a 90-kDa protein that can bind to the p53 tumor
      suppressor protein and negatively regulate its functions in transcription, cell
      cycle arrest, and apoptosis. The mdm2 gene is frequently amplified in human
      sarcomas, which may be responsible for the malignant transformations. We present
      evidence that the mdm2 oncoprotein is cleaved by an interleukin 1beta-converting
      enzyme-like protease (caspase) during p53-mediated apoptosis. The protease that
      cleaves mdm2 has a specificity similar to that of CPP32 (caspase-3), and
      recombinant caspase-3 is able to cleave mdm2 in vitro. The protease cleavage site
      has been mapped to between residue 361 and 362 of human mdm2. The proteolytic
      cleavage removes the COOH-terminal RING finger domain of mdm2, resulting in the
      loss of RNA binding activity. The p53 binding and inhibition functions of mdm2
      are not affected by the cleavage. The cleavage site sequence of mdm2 is
      evolutionarily conserved, suggesting that regulation by caspase cleavage during
      apoptosis is an important feature of mdm2.

PMID- 9278462
TI  - A comparison of low-molecular-weight heparin with unfractionated heparin for
      acute pulmonary embolism. The THESEE Study Group. Tinzaparine ou Heparine
      Standard: Evaluations dans l'Embolie Pulmonaire.
AB  - BACKGROUND: Low-molecular-weight heparin appears to be at least as effective and
      safe as standard, unfractionated heparin for the treatment of deep-vein
      thrombosis, but only limited data are available on the use of low-molecular
      weight heparin to treat acute symptomatic pulmonary embolism. METHODS: We
      randomly assigned 612 patients with symptomatic pulmonary embolism who did not
      require thrombolytic therapy or embolectomy to either subcutaneous low-molecular
      weight heparin (tinzaparin) given once daily in a fixed dose or adjusted-dose,
      intravenous unfractionated heparin. Oral anticoagulant therapy was begun between
      the first and the third day and was given for at least three months. We compared
      the treatments at day 8 and day 90 with respect to a combined end point of
      recurrent thromboembolism, major bleeding, and death. RESULTS: In the first eight
      days of treatment, 9 of 308 patients assigned to receive unfractionated heparin
      (2.9 percent) reached at least one of the end points, as compared,with 9 of 304
      patients assigned to low-molecular-weight heparin (3.0 percent; absolute
      difference, 0.1 percentage point; 95 percent confidence interval, -2.7 to 2.6).
      By day 90, 22 patients assigned to unfractionated heparin (7.1 percent) and 18
      patients assigned to low-molecular-weight heparin (5.9 percent) had reached at
      least one end point (P=0.54; absolute difference, 1.2 percentage points; 95
      percent confidence interval, -2.7 to 5.1). The risk of major bleeding was similar
      in the two treatment groups throughout the study. CONCLUSIONS: Under the
      conditions of this study, initial subcutaneous therapy with the low-molecular
      weight heparin tinzaparin appeared to be as effective and safe as intravenous
      unfractionated heparin in patients with acute pulmonary embolism.

PMID- 9278463
TI  - Effect of calcium and vitamin D supplementation on bone density in men and women
      65 years of age or older.
AB  - BACKGROUND: Inadequate dietary intake of calcium and vitamin D may contribute to
      the high prevalence of osteoporosis among older persons. METHODS: We studied the
      effects of three years of dietary supplementation with calcium and vitamin D on
      bone mineral density, biochemical measures of bone metabolism, and the incidence
      of nonvertebral fractures in 176 men and 213 women 65 years of age or older who
      were living at home. They received either 500 mg of calcium plus 700 IU of
      vitamin D3 (cholecalciferol) per day or placebo. Bone mineral density was
      measured by dual-energy x-ray absorptiometry, blood and urine were analyzed every
      six months, and cases of nonvertebral fracture were ascertained by means of
      interviews and verified with use of hospital records. RESULTS: The mean (+/-SD)
      changes in bone mineral density in the calcium-vitamin D and placebo groups were
      as follows: femoral neck, +0.50+/-4.80 and -0.70+/-5.03 percent, respectively
      (P=0.02); spine,+2.12+/-4.06 and +1.22+/-4.25 percent (P=0.04); and total body,
      +0.06+/-1.83 and -1.09+/-1.71 percent (P<0.001). The difference between the
      calcium-vitamin D and placebo groups was significant at all skeletal sites after
      one year, but it was significant only for total-body bone mineral density in the
      second and third years. Of 37 subjects who had nonvertebral fractures, 26 were in
      the placebo group and 11 were in the calcium-vitamin D group (P=0.02).
      CONCLUSIONS: In men and women 65 years of age or older who are living in the
      community, dietary supplementation with calcium and vitamin D moderately reduced
      bone loss measured in the femoral neck, spine, and total body over the three-year
      study period and reduced the incidence of nonvertebral fractures.

PMID- 9278464
TI  - Multidrug resistance in Yersinia pestis mediated by a transferable plasmid.

PMID- 9278465
TI  - Images in clinical medicine. Paradoxical embolism--thrombus in transit through a
      patent foramen ovale.

PMID- 9278466
TI  - Legionellosis.

PMID- 9278467
TI  - Low-molecular-weight heparins.

PMID- 9278468
TI  - The high price of product endorsement.

PMID- 9278469
TI  - Diet and the prevention of osteoporotic fractures.

PMID- 9278470
TI  - Multidrug resistance in plague.

PMID- 9278471
TI  - Welfare reform and the obstetrical care of immigrants and their newborns.

PMID- 9278472
TI  - The Oregon Health Plan--lessons for the nation. Second of two parts.

PMID- 9278473
TI  - Transcription factor access to chromatin.
AB  - The question of how sequence-specific transcription factors access their cognate
      sites in nucleosomally organized DNA is discussed on the basis of genomic
      footprinting data and chromatin reconstitution experiments. A classification of
      factors into two categories is proposed: (i) initiator factors which are able to
      bind their target sequences within regular nucleosomes and initiate events
      leading to chromatin remodelling and transactivation; (ii) effector factors which
      are unable to bind regular nucleosomes and depend on initiator factors or on a
      pre-set nucleosomal structure for accessing their target sequences in chromatin.
      Studies with the MMTV promoter suggest that the extent and number of protein-DNA
      contacts determine whether a factor belongs to one or the other category.
      Initiator factors have only a few DNA contacts clustered on one side of the
      double helix, whereas effector factors have extensive contacts distributed
      throughout the whole circumference of the DNA helix. Thus, the nature of DNA
      recognition confers to sequence-specific factors their specific place in the
      sequential hierarchy of gene regulatory events.

PMID- 9278474
TI  - The Elav-like proteins bind to AU-rich elements and to the poly(A) tail of mRNA.
AB  - The Elav-like proteins are specific mRNA binding proteins which are required for
      cellular differentiation. They contain three characteristic RNP2/RNP1-type RNA
      binding motifs. Previously we have shown that the first and second RNA binding
      domains bind to AU-rich elements in the 3'-UTR of mRNA. In this paper we show
      that the Elav-like proteins exhibit poly(A) binding activity. This activity is
      distinct from poly(A) binding activities that have been previously described. The
      Elav-like proteins specifically bind to long chain poly(A) tails. We have shown
      that the third RNA binding domain encompasses this poly(A) binding activity.
      Using poly(A)-Sepharose beads in a 'sandwich' assay we have shown that the Elav
      like proteins can bind simultaneously to the AU-rich element and to the poly(A)
      tail.

PMID- 9278475
TI  - Genetic evidence for selective degradation of RNA polymerase subunits by the 20S
      proteasome in Saccharomyces cerevisiae.
AB  - scs32 was isolated as an extragenic suppressor of a temperature-sensitive (ts)
      mutation (rpo26-31) in the gene encoding Rpo26p, a subunit common to yeast
      nuclear RNA polymerases (RNAPs). rpo26-31 also confers inositol auxotrophy,
      inhibits the assembly of RNAPI and RNAPII and reduces the steady-state level of
      Rpo26p and the largest subunit of RNAPI (Rpo11p or A190p) and RNAPII (Rpo21p).
      rpo26-31p accumulated to wild-type levels in the scs32 strain; nevertheless, the
      amount of assembled RNAPII remained at a reduced level at high temperature.
      Hence, scs32 only partially suppressed the ts phenotype and was unable to
      suppress the Ino-phenotype of rpo26-31. SCS32 is identical to PUP3, which encodes
      a subunit of the yeast proteasome. scs32 was able to suppress the phenotype of
      other ts alleles of RPO26, all of which reduce the steady-state level of this
      subunit. However, scs32 was unable to suppress the ts phenotype of mutant alleles
      of RPO21, or result in accumulation of the unstable rpo21-4p. These observations
      suggest that the stability of non-functional or unassembled forms of Rpo26p and
      Rpo21p are regulated independently.

PMID- 9278477
TI  - A competitive enzyme hybridization assay for plasma determination of
      phosphodiester and phosphorothioate antisense oligonucleotides.
AB  - An enzyme competitive hybridization assay was developed and validated for
      determination of mouse plasma concentrations of a 15mer antisense phosphodiester
      oligodeoxyribonucleotide and of two phosphorothioate analogs. Assays were
      performed in 96-well microtiter plates. The phosphodiester sense sequence was
      covalently bound to the microwells. The 5'-biotinylated antisense sequence was
      used as tracer. The principle of the assay involves competitive hybridization of
      tracer and antisense nucleotide to the solid phase-immobilized sense
      oligonucleotide. Solid phase- bound tracer oligonucleotide was assayed after
      reaction with a streptavidin-acetylcholinesterase conjugate, using the
      colorimetric method of Ellman. As in competitive enzyme immunoassays, coloration
      was inversely related to the amount of analyte initially present in the sample.
      The limit of quantification was 900 pM for phosphodiester antisense
      oligonucleotide using a 100 microl volume of plasma without extraction. Cross
      reactivity was negligible after a four base deletion in either the 3'or
      5'position. The assay was simple and sensitive, suitable for in vitro screening
      of oligonucleotide hybridization potency in biological fluids and for measuring
      the plasma pharmacokinetics of phosphorothioate and phosphodiester sequences.

PMID- 9278478
TI  - Evaluation of 3-ethoxy-1,2,4-dithiazoline-5-one (EDITH) as a new sulfurizing
      reagent in combination with labile exocyclic amino protecting groups for solid
      phase oligonucleotide synthesis.
AB  - 3-ethoxy-1,2,4-dithiazoline-5-one (EDITH) was recently introduced as an efficient
      sulfurizing reagent for solid-phase oligonucleotide synthesis. The successful
      syntheses were performed using standard base protecting groups (i.e. benzoyl for
      A and C, isobutyryl for G), which required deprotection in concentrated ammonium
      hydroxide at 55 degrees C for 15-18 h. We have explored the possibility of using
      EDITH in combination with fast deprotection chemistry(e.g. Expedite Chemistry
      using tert -butylphenoxy acetyl as a base protecting group). Surprisingly, poor
      synthesis performance was observed when syntheses were conducted with EDITH,
      Expedite Chemistry and standard synthesis cycle (i.e. Coupling-Thio-Cap).
      Potential G modification seemed to be the source of incompatibility since
      sequences containing no G or carrying isobutyryl- protected G residues could be
      synthesized with high efficiency. However, the deleterious G modification can be
      readily eliminated by inserting a capping step before the sulfurization reaction.
      Oligomers prepared with the Coupling-Cap-Thio-Cap cycle contained few
      phosphodiester contaminants as measured by31P-NMR, anion-exchange HPLC and MALDI
      TOF mass spectrometry. In addition to reducing deprotection time, this new
      combination also provides a mild method for the preparation of certain
      phosphorothioate oligomers that may be sensitive to prolonged ammonia treatment
      (e.g. thioated RNAs).

PMID- 9278476
TI  - Making (anti)sense of non-coding sequence conservation.
AB  - A substantial fraction of vertebrate mRNAs contain long conserved blocks in their
      untranslated regions as well as long blocks without silent changes in their
      protein coding regions. These conserved blocks are largely comprised of unique
      sequence within the genome, leaving us with an important puzzle regarding their
      function. A large body of experimental data shows that these regions are
      associated with regulation of mRNA stability. Combining this information with the
      rapidly accumulating data on endogenous antisense transcripts, we propose that
      the conserved sequences form long perfect duplexes with antisense transcripts.
      The formation of such duplexes may be essential for recognition by post
      transcriptional regulatory systems. The conservation may then be explained by
      selection against the dominant negative effect of allelic divergence.

PMID- 9278479
TI  - A computational genomics approach to the identification of gene networks.
AB  - To delineate the astronomical number of possible interactions of all genes in a
      genome is a task for which conventional experimental techniques are ill-suited.
      Sorely needed are rapid and inexpensive methods that identify candidates for
      interacting genes, candidates that can be further investigated by experiment.
      Such a method is introduced here for an important class of gene interactions,
      i.e., transcriptional regulation via transcription factors (TFs) that bind to
      specific enhancer or silencer sites. The method addresses the question: which of
      the genes in a genome are likely to be regulated by one or more TFs with known
      DNA binding specificity? It takes advantage of the fact that many TFs show
      cooperativity in transcriptional activation which manifests itself in closely
      spaced TF binding sites. Such 'clusters' of binding sites are very unlikely to
      occur by chance alone, as opposed to individual sites, which are often abundant
      in the genome. Here, statistical information about binding site clusters in the
      genome, is complemented by information about (i) known biochemical functions of
      the TF, (ii) the structure of its binding site, and (iii) function of the genes
      near the cluster, to identify genes likely to be regulated by a given
      transcription factor. Several applications are illustrated with the genome of
      Saccharomyces cerevisiae , and four different DNA binding activities, SBF, MBF, a
      sub-class of bHLH proteins and NBF. The technique may aid in the discovery of
      interactions between genes of known function, and the assignment of biological
      functions to putative open reading frames.

PMID- 9278480
TI  - The integrase family of tyrosine recombinases: evolution of a conserved active
      site domain.
AB  - The integrases are a diverse family of tyrosine recombinases which rearrange DNA
      duplexes by means of conservative site-specific recombination reactions. Members
      of this family, of which the well-studied lambda Int protein is the prototype,
      were previously found to share four strongly conserved residues, including an
      active site tyrosine directly involved in transesterification. However, few
      additional sequence similarities were found in the original group of 27 proteins.
      We have now identified a total of 81 members of the integrase family deposited in
      the databases. Alignment and comparisons of these sequences combined with an
      evolutionary analysis aided in identifying broader sequence similarities and
      clarifying the possible functions of these conserved residues. This analysis
      showed that members of the family aggregate into subfamilies which are consistent
      with their biological roles; these subfamilies have significant levels of
      sequence similarity beyond the four residues previously identified. It was also
      possible to map the location of conserved residues onto the available crystal
      structures; most of the conserved residues cluster in the predicted active site
      cleft. In addition, these results offer clues into an apparent discrepancy
      between the mechanisms of different subfamilies of integrases.

PMID- 9278481
TI  - Kinetics of phosphorothioate oligonucleotide metabolism in biological fluids.
AB  - The in vitro stability and metabolism of GEM[91, a 25mer phosphorothioate
      antisense oligonucleotide complementary to the gag mRNA region of HIV-1, was
      investigated using capillary electrophoresis (CE). The in vitro degradation of
      the parent compound at 37 degrees C was followed over the course of 120 h in
      human plasma. A CE method using laser-induced fluorescence detection was able to
      detect 5'-end intact metabolites including the parent compound extracted from
      biological fluids. Because the primary metabolic pathway is believed to be via 3'
      exonuclease activity, the results of this study were compared with the stability
      of the compound in a solution containing 3'-exonuclease. The numerical solution
      of sequential first-order reactions was used to obtain kinetic parameters.
      Exonuclease digestion of the parent compound, as measured using an automated CE
      UV instrument, yielded striking similarities between the two in vitro systems as
      well as between in vitro and in vivo systems.

PMID- 9278483
TI  - Hydroquinone-O,O'-diacetic acid ('Q-linker') as a replacement for succinyl and
      oxalyl linker arms in solid phase oligonucleotide synthesis.
AB  - When hydroquinone-O,Ooffiacetic acid is used as a linker arm in solid phase
      oligonucleotide synthesis, the time for NH4OH cleavage of oligodeoxy- or
      oligoribonucleotides is reduced to only 2 min. This allows increased productivity
      on automated DNA synthesizers without requiring any other modifications to
      existing reagents or synthesis and deprotection methods. The Q-linker may also be
      rapidly cleaved by milder reagents such as 5% NH4OH, potassium carbonate,
      anhydrous ammonia, t-butylamine or fluoride ion. However, the Q-linker is
      sufficiently stable for long-term storage at room temperature without degradation
      and no loss of material occurs during synthesis. The linker is also reasonably
      resistant to 20% piperidine/DMF, 0.5 M DBU/pyridine and 1:1
      triethylamine/ethanol. The Q-linker can therefore serve as a general replacement
      for both succinyl and oxalyl linker arms.

PMID- 9278482
TI  - The transcriptional activation and repression domains of RFX1, a context
      dependent regulator, can mutually neutralize their activities.
AB  - EP is a DNA element found in regulatory regions of viral and cellular genes.
      While being a key functional element in viral enhancers, EP has no intrinsic
      enhancer activity but can stimulate or silence transcription in a context
      dependent manner. The EP element is bound by RFX1, which belongs to a novel,
      evolutionarily conserved protein family. In an attempt to decipher the mechanism
      by which EP regulates transcription, the intrinsic transcriptional activity of
      RFX1 was investigated. A functional dissection of RFX1, by analysis of deletion
      mutants and chimeric proteins, identified several regions with independent
      transcriptional activity. An activation domain containing a glutamine-rich region
      is found in the N-terminal half of RFX1, while a region with repressor activity
      overlaps the C-terminal dimerization domain. In RFX1 these activities were
      mutually neutralized, producing a nearly inactive transcription factor. This
      neutralization effect was reproduced by fusing RFX1 sequences to a heterologous
      DNA-binding domain. We propose that relief of self-neutralization may allow RFX1
      to act as a dual-function regulator via its activation and repression domains,
      accounting for the context-dependent activity of EP.

PMID- 9278484
TI  - Reduced RNA polymerase II transcription in extracts of cockayne syndrome and
      xeroderma pigmentosum/Cockayne syndrome cells.
AB  - The hereditary disease Cockayne syndrome (CS) is a complex clinical syndrome
      characterized by arrested post-natal growth as well as neurological and other
      defects. The CSA and CSB genes are implicated in this disease. The clinical
      features of CS can also accompany the excision repair-defective hereditary
      disorder xeroderma pigmentosum (XP) from genetic complementation groups B, D or
      G. The XPB and XPD proteins are subunits of RNA polymerase II (RNAP II)
      transcription factor IIH (TFIIH). We show here that extracts of CS-A and CS-B
      cells, as well as those from XP-B/CS cells, support reduced levels of RNAP II
      transcription in vitro and that this feature is dependent on the state or quality
      of the template.

PMID- 9278485
TI  - Mutation frequencies at codon 248 of the p53 tumour suppressor gene are not
      increased in colon cancer cell lines with the RER+ phenotype.
AB  - The replication-error positive (RER+) phenotype characterizes tumour cells with
      microsatellite instability. This 'mutator phenotype' is thought to induce spread
      mutations throughout the genome, thus increasing the risk of tumour development.
      Here we analyse spontaneously arising mutations at the tetranucleotide CCGG ( Msp
      I recognition site), at positions 14 067-14 070 of the p53 gene sequence, in
      three colon cancer cell lines, two with microsatellite instability and one
      without this characteristic. This restriction site covers hot-spot codon 248,
      which is often mutated in colon carcinomas. Using the Msp I RFLP-PCR assay we
      found that the mean mutation frequency at this site was not different among the
      cell lines considered. Taking the substitutions separately, none of the mutations
      involving codon 248 arose with significantly higher frequency in each of the RER+
      cell lines (HCT116 and DLD1) compared with the RER-one (SW480). Only the CG
      transversion at nt 14 067 (codon 247) occurred with a slightly higher, but
      biologically insignificant, frequency in one of the RER+ cell lines (HCT116). Our
      in vitro data support the previously reported lack of correlation between
      microsatellite instability and p53 mutations in RER+ tumour specimens.

PMID- 9278486
TI  - Mutational analysis of vaccinia virus topoisomerase identifies residues involved
      in DNA binding.
AB  - Vaccinia DNA topoisomerase catalyzes the cleavage and re-joining of DNA strands
      through a DNA-(3'-phosphotyrosyl)-enzyme intermediate formed at a specific target
      sequence, 5'-(C/T)CCTT downward arrow. The 314 aa protein consists of three
      protease-resistant structural domains demarcated by protease-sensitive
      interdomain segments referred to as the bridge and the hinge. The bridge is
      defined by trypsin-accessible sites at Arg80, Lys83 and Arg84. Photocrosslinking
      and proteolytic footprinting experiments suggest that residues near the
      interdomain bridge interact with DNA. To assess the contributions of specific
      amino acids to DNA binding and transesterification chemistry, we introduced
      alanine substitutions at 16 positions within a 24 aa segment from residues 63 to
      86(DSKGRRQYFYGKMHVQNRNAKRDR). Assays of the rates of DNA relaxation under
      conditions optimal for the wild-type topoisomerase revealed significant
      mutational effects at six positions; Arg67, Tyr70, Tyr72, Arg80, Arg84 and Asp85.
      The mutated proteins displayed normal or near-normal rates of single-turnover
      transesterification to DNA. The effects of amino acid substitutions on DNA
      binding were evinced by inhibition of covalent adduct formation in the presence
      of salt and magnesium. The mutant enzymes also displayed diminished affinity for
      a subset of cleavage sites in pUC19 DNA. Tyr70 and Tyr72 were subjected to
      further analysis by replacement with Phe, His, Gln and Arg. At both positions,
      the aromatic moiety was important for DNA binding.

PMID- 9278488
TI  - FLP-mediated DNA mobilization to specific target sites in Drosophila chromosomes.
AB  - The ability to place a series of gene constructs at a specific site in the genome
      opens new possibilities for the experimental examination of gene expression and
      chromosomal position effects. We report that the FLP- FRT site-specific
      recombination system of the yeast 2mu plasmid can be used to integrate DNA at a
      chromosomal FRT target site in Drosophila. The technique we used was to first
      integrate an FRT- flanked gene by standard P element-mediated transformation. FLP
      was then used to excise the FRT- flanked donor DNA and screen for FLP-mediated re
      integration at an FRT target at a different chromosome location. Such events were
      recovered from up to 5% of the crosses used to screen for mobilization and are
      easily detectable by altered linkage of a white reporter gene or by the
      generation of a white + gene upon integration.

PMID- 9278487
TI  - Glucose represses the lactose-galactose regulon in Kluyveromyces lactis through a
      SNF1 and MIG1- dependent pathway that modulates galactokinase (GAL1) gene
      expression.
AB  - Expression of the lactose-galactose regulon in Kluyveromyces lactis is induced by
      lactose or galactose and repressed by glucose. Some components of the induction
      and glucose repression pathways have been identified but many remain unknown. We
      examined the role of the SNF1 (KlSNF1) and MIG1 (KlMIG1) genes in the induction
      and repression pathways. Our data show that full induction of the regulon
      requires SNF1; partial induction occurs in a Klsnf1 -deleted strain, indicating
      that a KlSNF1 -independent pathway(s) also regulates induction. MIG1 is required
      for full glucose repression of the regulon, but there must be a KlMIG1 
      independent repression pathway also. The KlMig1 protein appears to act downstream
      of the KlSnf1 protein in the glucose repression pathway. Most importantly, the
      KlSnf1-KIMig repression pathway operates by modulating KlGAL1 expression.
      Regulating KlGAL1 expression in this manner enables the cell to switch the
      regulon off in the presence of glucose. Overall, our data show that, while the
      Snf1 and Mig1 proteins play similar roles in regulating the galactose regulon in
      Saccharomyces cerevisiae and K.lactis , the way in which these proteins are
      integrated into the regulatory circuits are unique to each regulon, as is the
      degree to which each regulon is controlled by the two proteins.

PMID- 9278489
TI  - A new method of synthesis of fluorescently labelled oligonucleotides and their
      application in DNA sequencing.
AB  - A new approach to the chemical synthesis of oligodeoxynucleotides bearing
      reporter functional groups at base residues of 3'-end nucleosides is reported.
      Applications of the 3'-end fluorescently labelled primers for automated DNA
      sequencing are shown.

PMID- 9278490
TI  - Fine mapping of replication origins (ori A and ori B) in Nicotiana tabacum
      chloroplast DNA.
AB  - Using a partially purified replication complex from tobacco chloroplasts,
      replication origins have been localized to minimal sequences of 82 (pKN8,
      positions 137 683-137 764) and 243 bp (pKN3, positions 130 513-130 755) for ori A
      and ori B respectively. Analysis of in vitro replication products by two
      dimensional agarose gel electrophoresis showed simple Y patterns for single ori
      sequence-containing clones, indicative of rolling circle replication. Double Y
      patterns were observed when a chloroplast DNA template containing both ori s
      (pKN9) was tested. Dpn I analysis and control assays with Escherichia coli DNA
      polymerase provide a clear method to distinguish between true replication and DNA
      repair synthesis. These controls also support the reliability of this in vitro
      chloroplast DNA replication system. EM analysis of in vitro replicated products
      showed rolling circle replication intermediates for single ori clones (ori A or
      ori B), whereas D loops were observed for a clone (pKN9) containing both ori s.
      The minimal ori regions contain sequences which are capable of forming stem-loop
      structures with relatively high free energy and other sequences which interact
      with specific protein(s) from the chloroplast replication fraction. Apparently
      the minimal ori sequences reported here contain all the necessary elements for
      support of chloroplast DNA replication in vitro.

PMID- 9278491
TI  - Substrate DNA and cofactor regulate the activities of a multi-functional
      restriction-modification enzyme, BcgI.
AB  - The BcgI restriction-modification system consists of two subunits, A and B. It is
      a bifunctional protein complex which can cleave or methylate DNA. The regulation
      of these competing activities is determined by the DNA substrates and cofactors.
      BcgI is an active endonuclease and a poor methyltransferase on unmodified DNA
      substrates. In contrast, BcgI is an active methyltransferase and an inactive
      endonuclease on hemimethylated DNA substrates. The cleavage and methylation
      reactions share cofactors. While BcgI requires Mg2+and S -adenosyl methionine
      (AdoMet) for DNA cleavage, its methylation reaction requires only AdoMet and yet
      is significantly stimulated by Mg2+. Site-directed mutagenesis was carried out to
      investigate the relationship between AdoMet binding and BcgI DNA
      cleavage/methylation activities. Most substitutions of conserved residues forming
      the AdoMet binding pocket in the A subunit abolished both methylation and
      cleavage activities, indicating that AdoMet binding is an early common step
      required for both cleavage and methylation. However, one mutation (Y439A)
      abolished only the methylation activity, not the DNA cleavage activity. This
      mutant protein was purified and its methylation, cleavage and AdoMet binding
      activities were tested in vitro . BcgI-Y439A had no detectable methylation
      activity, but it retained 40% of the AdoMet binding and DNA cleavage activities.

PMID- 9278492
TI  - Histone deacetylases, acetoin utilization proteins and acetylpolyamine
      amidohydrolases are members of an ancient protein superfamily.
AB  - Searches of several sequence databases reveal that human HD1, yeast HDA1, yeast
      RPD3 and other eukaryotic histone deacetylases share nine motifs with archaeal
      and eubacterial enzymes, including acetoin utilization protein (acuC) and
      acetylpolyamine amidohydrolase. Histone deacetylase and acetylpolyamine
      amidohydrolase also share profound functional similarities in that both: (i)
      recognize an acetylated aminoalkyl group; (ii) catalyze the removal of the acetyl
      group by cleaving an amide bond; (iii) increase the positive charge of the
      substrate. Stabilization of nucleosomal DNA-histone interaction brought about by
      the change in charge has been implicated as the underlying cause for histone
      deacetylase-mediated transcriptional repression. We speculate that the eukaryotic
      histone deacetylases originated from a prokaryotic enzyme similar to the
      acetylpolyamine amidohydrolases that relied on reversible acetylation and
      deacetylation of the aminoalkyl group of a DNA binding molecule to achieve a gene
      regulatory effect.

PMID- 9278493
TI  - dGTP-dependent processivity and possible template switching of euplotes
      telomerase.
AB  - We have measured the processivity of telomeric DNA extension by Euplotes
      aediculatus telomerase at various concentrations of the nucleotide substrates
      dGTP and dTTP. The maximum processivity (approximately 3 repeats) was observed at
      approximately 100 microM of each dNTP. Processivity decreased as the dNTP
      concentrations were reduced and, surprisingly, as the concentration of dGTP was
      increased. Also, the characteristic banding pattern generated by telomerase
      extension of DNA primers shifted in response to changes in dGTP concentration.
      One pattern with 8 nt periodicity was predominant at dGTP concentrations </=16
      microM, while at >/= 250 microM an 8 nt repeat pattern out-of-phase with the
      first was observed; at intermediate concentrations the two patterns coexisted. We
      propose that two different segments of the RNA subunit can serve as the template
      for repeat synthesis; nt 42-49 at low dGTP concentrations and nt 36-43 at high
      dGTP concentrations. An alternative model for the low dGTP pattern involves an
      internal pause site but no pause at the end of the template and is, therefore,
      considered less likely. Because the effects of dGTP on processivity and banding
      pattern appear to be distinct from nucleotide binding in the polymerase active
      site, we propose a second dGTP binding site involved in template selection and
      processivity.

PMID- 9278494
TI  - A functional YY1 binding site is necessary and sufficient to activate Surf-1
      promoter activity in response to serum growth factors.
AB  - The human Surf-1 and Surf-2 housekeeping genes are divergently transcribed and
      share a bi-directional, TATA-less promoter. Housekeeping promoters typically
      contain complex arrays of transcription factor binding sites and several studies
      have suggested that many of these sites might be functionally redundant. The Surf
      1/Surf-2 promoter region contains four factor binding sites; members of the ETS
      family of transcription factors bind to two of these sites whilst YY1 binds to a
      third site immediately downstream of the major Surf-1 transcription start point.
      Here we show that Sp1 binds to the fourth transcription factor binding site.
      Although YY1 and Sp1 have previously been shown to interact both in vitro and in
      vivo, these proteins function independently at the Surf-1/Surf-2 promoter. The
      binding of Sp1 alone is sufficient to bring about full promoter activity in the
      Surf-2 direction. In contrast, both Sp1 and ETS proteins are required to bring
      about full promoter activity in the Surf-1 direction. The YY1 binding site is not
      required for basal transcription in either direction. The YY1 binding site is,
      however, both necessary and sufficient to confer growth factor inducibility on
      transcription in the Surf-1 direction. Our data suggest that functionally
      redundant transcription factor binding sites might not be a general feature of
      housekeeping promoters.

PMID- 9278495
TI  - Sp3 is a transcriptional activator of the human alpha2(I) collagen gene.
AB  - Sp3 is an ubiquitously expressed transcription factor, closely related to Sp1
      but, unlike Sp1, it often functions as a transcriptional repressor. In this study
      we investigated the role of Sp3 in regulating the transcription of the human
      alpha2(I) collagen gene. We show that Sp1 and Sp3 specifically bind to three of
      the previously characterized cis -elements in this promoter, including two
      positive cis-elements between -303 and -271 and -128 and -123, and a repressor
      site between -164 and -159, but do not bind to the fourth cis-element bound by
      CBF. Functional analyses of Sp3 and Sp1 in Drosophila cells indicate that each
      protein transactivates the human alpha2(I) collagen promoter with equal potency
      and, when tested together, have an additive effect on the promoter activity.
      Furthermore, in vitro transcription assays demonstrate that both Sp1 and Sp3 are
      capable of supporting transcription from the collagen promoter independently of
      each other. However, when activities of both Sp1 and Sp3 are blocked with
      specific antibodies, in vitro transcription from this promoter is almost
      completely abolished. The results of this study demonstrate that Sp3 is as potent
      an activator of the human alpha2(I) collagen promoter as is Sp1 and that a
      transcriptional activity of the human alpha2(I) promoter is dependent on both
      proteins.

PMID- 9278496
TI  - Oligonucleotides with conjugated dihydropyrroloindole tripeptides: base
      composition and backbone effects on hybridization.
AB  - The ability of conjugated minor groove binding (MGB) residues to stabilize
      nucleic acid duplexes was investigated by synthesis of oligonucleotides bearing a
      tethered dihydropyrroloindole tripeptide (CDPI3). Duplexes bearing one or more of
      these conjugated MGBs were varied by base composition (AT- or GC-rich
      oligonucleotides), backbone modifications (phosphodiester DNA, 2'-O-methyl
      phosphodiester RNA or phosphorothioate DNA) and site of attachment of the MGB
      moiety (5'- or 3'-end of either duplex strand). Melting temperatures of the
      duplexes were determined. The conjugated CDPI3 residue enhanced the stability of
      virtually all duplexes studied. The extent of stabilization was backbone and
      sequence dependent and reached a maximum value of 40-49 degrees C for d(pT)8.
      d(pA)8. Duplexes with a phosphorothioate DNA backbone responded similarly on
      CDPI3 conjugation, although they were less stable than analogous phosphodiesters.
      Modest stabilization was obtained for duplexes with a 2'-O-methyl RNA backbone.
      The conjugated CDPI3 residue stabilized GC-rich DNA duplexes, albeit to a lesser
      extent than for AT-rich duplexes of the same length.

PMID- 9278497
TI  - Finding the most significant common sequence and structure motifs in a set of RNA
      sequences.
AB  - We present a computational scheme to locally align a collection of RNA sequences
      using sequence and structure constraints. In addition, the method searches for
      the resulting alignments with the most significant common motifs, among all
      possible collections. The first part utilizes a simplified version of the Sankoff
      algorithm for simultaneous folding and alignment of RNA sequences, but maintains
      tractability by constructing multi-sequence alignments from pairwise comparisons.
      The algorithm finds the multiple alignments using a greedy approach and has
      similarities to both CLUSTAL and CONSENSUS, but the core algorithm assures that
      the pairwise alignments are optimized for both sequence and structure
      conservation. The choice of scoring system and the method of progressively
      constructing the final solution are important considerations that are discussed.
      Example solutions, and comparisons with other approaches, are provided. The
      solutions include finding consensus structures identical to published ones.

PMID- 9278498
TI  - Binding of NF1 to the MMTV promoter in nucleosomes: influence of rotational
      phasing, translational positioning and histone H1.
AB  - To analyse the role of rotational orientation and translational positioning of
      nucleosomal DNA on transcription factor binding we have generated a series of
      mutant MMTV promoters containing insertions of various lengths between the
      hormone-responsive region and the binding site for NF1. These various MMTV
      promoter fragments were assembled in mononucleosomes and used for structural
      studies and binding experiments. We show that the insertions change the
      rotational phase and translational positioning of the NF1 site as predicted if
      the sequences upstream of the insertion site were the main determinants of
      nucleosome phasing. In band shift experiments with recombinant NF1 we cannot
      detect binding of the protein to NF1 sites included within the limits of a
      nucleosome, independent of their rotational orientation. Moving the NF1 site
      closer to the nucleosome border also did not permit NF1 binding. This behaviour
      probably reflects the way NF1 binds DNA, namely it almost completely surrounds
      the circumference of the double helix establishing a large number of contacts
      with the bases and the backbone. In contrast to the wild-type and short insertion
      mutants, NF1 bound readily to nucleosomes containing 30 or 50 bp insertions which
      placed the NF1 site at the nucleosome edge or within linker DNA. NF1 binding to
      the linker DNA was unaffected by incorporation of histone H1 into the nucleosome
      particle. These findings are discussed in relation to chromatin remodelling
      initiated by steroid hormones during induction of the MMTV promoter.

PMID- 9278499
TI  - Use of the two-hybrid system to identify protein-protein interaction temperature
      sensitive mutants: application to the CDK2/p21Cip1 interaction.
AB  - We describe the application of the two-hybrid system to the identification of
      protein-protein interaction temperature-sensitive mutants. We applied this
      strategy to the interaction between the human CDK2 cell cycle regulator and the
      p21Cip1 regulatory subunit. A library of randomly generated CDK2 mutant proteins
      was screened for interaction with p21Cip1 at different temperatures. This
      approach resulted in the isolation of single point mutations in CDK2 causing
      temperature-sensitive interaction with p21Cip1. Our results demonstrate that the
      two-temperature two-hybrid screen is an efficient approach for the rational
      design and screening of protein-protein interaction conditional mutations.

PMID- 9278500
TI  - A transgenic mouse strain expressing four drug-selectable marker genes.
AB  - Murine embryonic stem (ES) cells are commonly cultured on feeder layers of
      primary murine embryonic fibroblasts (MEFs). Because gene targeting experiments
      often involve sequential selection for multiple-drug resistance in single ES cell
      lines, we have developed a new mouse strain which represents an economical donor
      for the production of multiple-drug resistant MEFs. MEFs prepared from the DR-4
      mouse strain displayed resistance to concentrations of the drugs G418, 6
      thioguanine, puromycin and hygromycin well above those used normally for the
      selection of drug-resistant ES cells.

PMID- 9278501
TI  - Fluorescence-, isotope- or biotin-labeling of the 5 '-end of single-stranded
      DNA/RNA using T4 RNA ligase.
AB  - A rapid 5'-labeling method of single-stranded DNA/RNA was developed, which is
      based on the utilization of an adenylated intermediate in the reaction of T4 RNA
      ligase. This method is commonly useful for fluorescence-, isotope- or biotin
      labeling of the 5'-ends of both oligo- and polynucleotides.

PMID- 9278502
TI  - Multiplex genotyping of PCR products with MassTag-labeled primers.
AB  - A simple mass spectrometric based assay, the PinPoint assay, has previously been
      described for typing single nucleotide polymorphisms. The identity of a
      polymorphism is determined by mass differences of single base extended genotyping
      primers as determined by MALDI-TOF mass spectrometry. A simple method for
      multiplexing the assay is described, employing multiple primers with 5'oligo(dT)
      sequences (MassTags) which serve to mass discriminate the peaks of multiple
      extended and non-extended primers. The assay is extremely rapid and requires no
      labeling reagents.

PMID- 9278503
TI  - The complete genome sequence of Escherichia coli K-12.
AB  - The 4,639,221-base pair sequence of Escherichia coli K-12 is presented. Of 4288
      protein-coding genes annotated, 38 percent have no attributed function.
      Comparison with five other sequenced microbes reveals ubiquitous as well as
      narrowly distributed gene families; many families of similar genes within E. coli
      are also evident. The largest family of paralogous proteins contains 80 ABC
      transporters. The genome as a whole is strikingly organized with respect to the
      local direction of replication; guanines, oligonucleotides possibly related to
      replication and recombination, and most genes are so oriented. The genome also
      contains insertion sequence (IS) elements, phage remnants, and many other patches
      of unusual composition indicating genome plasticity through horizontal transfer.

PMID- 9278508
TI  - Detection of soft X-rays and a sensitive search for noble gases in comet Hale
      Bopp.
AB  - An image of comet Hale-Bopp (C/1995 O1) in soft x-rays reveals a central emission
      offset from the nucleus, as well as an extended emission feature that does not
      correlate with the dust jets seen at optical wavelengths. Neon was found to be
      depleted in the cometary ice by more than a factor of 25 relative to solar
      abundance, which suggests that ices in Hale-Bopp formed at (or later experienced)
      temperatures higher than 25 kelvin. A helium line emission at a wavelength of 584
      angstroms was detected and may be attributable to charge transfer of solar wind
      alpha particles in the cometary coma. Ionized oxygen and another helium line
      contribute to an emission observed at 538 angstroms.

PMID- 9278510
TI  - Cdc25 mitotic inducer targeted by chk1 DNA damage checkpoint kinase.
AB  - Arrest of the cell cycle at the G2 checkpoint, induced by DNA damage, requires
      inhibitory phosphorylation of the kinase Cdc2 in both fission yeast and human
      cells. The kinase Wee1 and the phosphatase Cdc25, which regulate Cdc2
      phosphorylation, were evaluated as targets of Chk1, a kinase essential for the
      checkpoint. Fission yeast cdc2-3w Deltacdc25 cells, which express activated Cdc2
      and lack Cdc25, were responsive to Wee1 but insensitive to Chk1 and irradiation.
      Expression of large amounts of Chk1 produced the same phenotype as did loss of
      the cdc25 gene in cdc2-3w cells. Cdc25 associated with Chk1 in vivo and was
      phosphorylated when copurified in Chk1 complexes. These findings identify Cdc25,
      but not Wee1, as a target of the DNA damage checkpoint.

PMID- 9278511
TI  - Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to
      Cdk regulation through Cdc25.
AB  - In response to DNA damage, mammalian cells prevent cell cycle progression through
      the control of critical cell cycle regulators. A human gene was identified that
      encodes the protein Chk1, a homolog of the Schizosaccharomyces pombe Chk1 protein
      kinase, which is required for the DNA damage checkpoint. Human Chk1 protein was
      modified in response to DNA damage. In vitro Chk1 bound to and phosphorylated the
      dual-specificity protein phosphatases Cdc25A, Cdc25B, and Cdc25C, which control
      cell cycle transitions by dephosphorylating cyclin-dependent kinases. Chk1
      phosphorylates Cdc25C on serine-216. As shown in an accompanying paper by Peng et
      al. in this issue, serine-216 phosphorylation creates a binding site for 14-3-3
      protein and inhibits function of the phosphatase. These results suggest a model
      whereby in response to DNA damage, Chk1 phosphorylates and inhibits Cdc25C, thus
      preventing activation of the Cdc2-cyclin B complex and mitotic entry.

PMID- 9278512
TI  - Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by
      phosphorylation of Cdc25C on serine-216.
AB  - Human Cdc25C is a dual-specificity protein phosphatase that controls entry into
      mitosis by dephosphorylating the protein kinase Cdc2. Throughout interphase, but
      not in mitosis, Cdc25C was phosphorylated on serine-216 and bound to members of
      the highly conserved and ubiquitously expressed family of 14-3-3 proteins. A
      mutation preventing phosphorylation of serine-216 abrogated 14-3-3 binding.
      Conditional overexpression of this mutant perturbed mitotic timing and allowed
      cells to escape the G2 checkpoint arrest induced by either unreplicated DNA or
      radiation-induced damage. Chk1, a fission yeast kinase involved in the DNA damage
      checkpoint response, phosphorylated Cdc25C in vitro on serine-216. These results
      indicate that serine-216 phosphorylation and 14-3-3 binding negatively regulate
      Cdc25C and identify Cdc25C as a potential target of checkpoint control in human
      cells.

PMID- 9278513
TI  - A cyanobacterial phytochrome two-component light sensory system.
AB  - The biliprotein phytochrome regulates plant growth and developmental responses to
      the ambient light environment through an unknown mechanism. Biochemical analyses
      demonstrate that phytochrome is an ancient molecule that evolved from a more
      compact light sensor in cyanobacteria. The cyanobacterial phytochrome Cph1 is a
      light-regulated histidine kinase that mediates red, far-red reversible
      phosphorylation of a small response regulator, Rcp1 (response regulator for
      cyanobacterial phytochrome), encoded by the adjacent gene, thus implicating
      protein phosphorylation-dephosphorylation in the initial step of light signal
      transduction by phytochrome.

PMID- 9278514
TI  - Differential ligand activation of estrogen receptors ERalpha and ERbeta at AP1
      sites.
AB  - The transactivation properties of the two estrogen receptors, ERalpha and ERbeta,
      were examined with different ligands in the context of an estrogen response
      element and an AP1 element. ERalpha and ERbeta were shown to signal in opposite
      ways when complexed with the natural hormone estradiol from an AP1 site: with
      ERalpha, 17beta-estradiol activated transcription, whereas with ERbeta, 17beta
      estradiol inhibited transcription. Moreover, the antiestrogens tamoxifen,
      raloxifene, and Imperial Chemical Industries 164384 were potent transcriptional
      activators with ERbeta at an AP1 site. Thus, the two ERs signal in different ways
      depending on ligand and response element. This suggests that ERalpha and ERbeta
      may play different roles in gene regulation.

PMID- 9278515
TI  - Binding of neuroligins to PSD-95.
AB  - PSD-95 is a component of postsynaptic densities in central synapses. It contains
      three PDZ domains that localize N-methyl-D-aspartate receptor subunit 2 (NMDA2
      receptor) and K+ channels to synapses. In mouse forebrain, PSD-95 bound to the
      cytoplasmic COOH-termini of neuroligins, which are neuronal cell adhesion
      molecules that interact with beta-neurexins and form intercellular junctions.
      Neuroligins bind to the third PDZ domain of PSD-95, whereas NMDA2 receptors and
      K+ channels interact with the first and second PDZ domains. Thus different PDZ
      domains of PSD-95 are specialized for distinct functions. PSD-95 may recruit ion
      channels and neurotransmitter receptors to intercellular junctions formed between
      neurons by neuroligins and beta-neurexins.

PMID- 9278516
TI  - Postsynaptic glutamate transport at the climbing fiber-Purkinje cell synapse.
AB  - The role of postsynaptic, neuronal glutamate transporters in terminating signals
      at central excitatory synapses is not known. Stimulation of a climbing fiber
      input to cerebellar Purkinje cells was shown to generate an anionic current
      mediated by glutamate transporters. The kinetics of transporter currents were
      resolved by pulses of glutamate to outside-out membrane patches from Purkinje
      cells. Comparison of synaptic transporter currents to transporter currents
      expressed in Xenopus oocytes suggests that postsynaptic uptake at the climbing
      fiber synapse removes at least 22 percent of released glutamate. These neuronal
      transporter currents arise from synchronous activation of transporters that
      greatly outnumber activated AMPA receptors.

PMID- 9278517
TI  - Dynamic molecular combing: stretching the whole human genome for high-resolution
      studies.
AB  - DNA in amounts representative of hundreds of eukaryotic genomes was extended on
      silanized surfaces by dynamic molecular combing. The precise measurement of
      hybridized DNA probes was achieved directly without requiring normalization. This
      approach was validated with the high-resolution mapping of cosmid contigs on a
      yeast artificial chromosome (YAC) within yeast genomic DNA. It was extended to
      human genomic DNA for precise measurements ranging from 7 to 150 kilobases, of
      gaps within a contig, and of microdeletions in the tuberous sclerosis 2 gene on
      patients' DNA. The simplicity, reproducibility, and precision of this approach
      makes it a powerful tool for a variety of genomic studies.

PMID- 9278519
TI  - Serotonergic inhibition of the T-type and high voltage-activated Ca2+ currents in
      the primary sensory neurons of Xenopus larvae.
AB  - The primary sensory Rohon-Beard (R-B) neurons of Xenopus larvae are highly
      analogous to the C fibers of the mammalian pain pathway. We explored the actions
      of 5-HT by studying the modulation of Ca2+ currents. In approximately 80% of the
      acutely isolated R-B neurons, 5-HT inhibited the high voltage-activated (HVA)
      currents by 16% (n = 29) and the T-type currents by 24% (n = 41). The modulation
      of the T-type and the HVA currents was mimicked by selective 5-HT1A and 5-HT1D
      agonists: 8-OH-DPAT and L-694,247. The effects of the agonists were blocked by
      their respective 5-HT1A or 5-HT1D antagonists: p-MPPI and GR127935, suggesting
      that both 5-HT1A and 5-HT1D receptors were involved. Approximately 70% of the
      actions of 5-HT on HVA currents was occluded by omega-conotoxin-GVIA (N-type
      channel blocker), whereas the rest of the modulation ( approximately 30%) was
      occluded by <100 nM omega-agatoxin-TK (P/Q-type channel blocker). This suggests
      that 5-HT acts on N- and P/Q-type Ca2+ channels. Neither the modulation of the T
      type nor that of the HVA currents was accompanied by changes in their voltage
      dependent kinetics. Cell-attached patch-clamp recordings suggest that the
      modulation of the T-type channel occurs through a membrane-delimited second
      messenger. We have studied the functional consequences of the modulation of T
      type Ca2+ channels and have found that these channels play a role in spike
      initiation in R-B neurons. Modulation of T-type channels by 5-HT therefore could
      modulate the sensitivity of this sensory pathway by increasing the thresholds of
      R-B neurons. This is a new and potentially important locus for modulation of
      sensory pathways in vertebrates.

PMID- 9278518
TI  - Conditional mutator phenotypes in hMSH2-deficient tumor cell lines.
AB  - Two human tumor cell lines that are deficient in the mismatch repair protein
      hMSH2 show little or no increase in mutation rate relative to that of a mismatch
      repair-proficient cell line when the cells are maintained in culture conditions
      allowing rapid growth. However, mutations accumulate at a high rate in these
      cells when they are maintained at high density. Thus the mutator phenotype of
      some mismatch repair-deficient cell lines is conditional and strongly depends on
      growth conditions. These observations have implications for tumor development
      because they suggest that mutations may accumulate in tumor cells when growth is
      limited.

PMID- 9278520
TI  - Heterogeneity of astrocyte resting membrane potentials and intercellular coupling
      revealed by whole-cell and gramicidin-perforated patch recordings from cultured
      neocortical and hippocampal slice astrocytes.
AB  - Astrocytes are thought to regulate the extracellular potassium concentration by
      mechanisms involving both voltage-dependent and transport-mediated ion fluxes
      combined with intercellular communication via gap junctions. Mechanisms
      regulating resting membrane potential (RMP) play a fundamental role in
      determining glial contribution to buffering of extracellular potassium and uptake
      of potentially toxic neurotransmitters. We have investigated the passive
      electrophysiological properties of cultured neocortical astrocytes and astrocytes
      recorded in hippocampal slices from 18-25 d postnatal rats. These experiments
      revealed a wide range of astrocyte RMPs that were independent of developmental
      factors, length of culturing, cellular morphology, the electrophysiological
      techniques used (whole-cell vs perforated recording), cell-specific expression of
      Na+/2HCO3- co-transporters, or voltage-dependent Na+ channels. Exposure of
      cultured astrocytes to differentiation-inducing factors (such as cAMP) or
      inhibition of proliferation (by serum deprivation) did not significantly
      influence RMP. Expression of ATP-sensitive potassium channels was absent in these
      glia; thus, K(ATP)-related mechanisms did not contribute to cell resting
      potential. In both cultured and slice astrocytes, spontaneous
      electrophysiological changes were commonly observed. These reversible events,
      which resulted in differential sensitivity to potassium channel blockers (cesium
      and barium) and sudden current-voltage profile changes, were attributable to
      dynamic changes in cell-to-cell coupling, as confirmed by recordings from
      isolated pairs of cells. We conclude that the heterogeneity of astrocytic RMP and
      intercellular coupling both in culture and in situ are intrinsic properties of
      glia that may contribute to transcellular transport of potassium. We propose a
      model in which spatial buffering may be facilitated by heterogeneous mechanisms
      controlling glial RMP in combination with dynamic changes in intercellular
      coupling.

PMID- 9278522
TI  - Modulation of force during locomotion: differential action of crustacean
      cardioactive peptide on power-stroke and return- stroke motor neurons.
AB  - Crustacean cardioactive peptide (CCAP) elicited expression of the motor pattern
      that drives coordinated swimmeret beating in crayfish and modulated this pattern
      in a dose-dependent manner. In each ganglion that innervates swimmerets, neurons
      with CCAP-like immunoreactivity sent processes to the lateral neuropils, which
      contain branches of swimmeret motor neurons and the local pattern-generating
      circuits. CCAP affected each of the four functional groups of motor neurons,
      power-stroke excitors (PSE), return-stroke excitors (RSE), power-stroke
      inhibitors (PSI), and return-stroke inhibitors (RSI), that innervate each
      swimmeret. When CCAP was superfused, the membrane potentials of these neurons
      began to oscillate periodically about their mean potentials. The mean potentials
      of PSE and RSI neurons depolarized, and some of these neurons began to fire
      during each depolarization. Both intensity and durations of PSE bursts increased
      significantly. The mean potentials of RSE and PSI neurons hyperpolarized, and
      these neurons were less likely to fire during each depolarization. When CCAP was
      superfused in a low Ca2+ saline that blocked chemical transmission, these changes
      in mean potential persisted, but the periodic oscillations disappeared. These
      results are evidence that CCAP acts at two levels: activation of local premotor
      circuits and direct modulation of swimmeret motor neurons. The action on motor
      neurons is differential; PSEs and RSIs are excited, but RSEs and PSIs are
      inhibited. The consequences of this selectivity are to increase intensity of
      bursts of impulses that excite power-stroke muscles.

PMID- 9278521
TI  - NAC-1, a rat brain mRNA, is increased in the nucleus accumbens three weeks after
      chronic cocaine self-administration.
AB  - Chronic cocaine use leads to biochemical and behavioral changes that can persist
      for weeks to months after drug administration is discontinued. Alterations in
      gene expression in the mammalian CNS may contribute to these long-term neural
      consequences of cocaine abuse. A combined in situ transcription-PCR amplification
      strategy was used to isolate a novel mRNA, NAC-1, from the nucleus accumbens of
      rats 3 weeks after discontinuing 3 weeks of intravenous cocaine self
      administration. In rats that self-administered cocaine, levels of NAC-1 were
      increased approximately 50% in the nucleus accumbens but not in the dorsal
      striatum or hippocampus, when compared with levels from yoked-saline controls. In
      situ hybridization analysis demonstrated increased numbers of NAC-1-expressing
      cells in the nucleus accumbens of rats who had self-administered cocaine. NAC-1
      mRNA exists as one form, approximately 4400 nucleotides (nt) in size, and also is
      present at much lower amounts in non-neural tissues. A full-length cDNA clone was
      isolated from a whole brain library. The predicted polypeptide sequence contains
      a POZ domain in the first 120 amino acids; the same POZ domain sequence mediates
      protein-protein interactions among some transcriptional regulators. NAC-1 mRNA
      levels were also increased in the nucleus accumbens 1 week after 6 d of
      noncontingent cocaine treatments. Regulation of NAC-1 mRNA in the nucleus
      accumbens demonstrates a long-term effect of cocaine use on cellular function
      that may be relevant in behavioral sensitization or cocaine self-administration.

PMID- 9278523
TI  - Dissection of functional domains of the voltage-dependent Ca2+ channel
      alpha2delta subunit.
AB  - Coexpression of the cloned voltage-dependent Ca2+ channel alpha2delta subunit
      with the pore-forming alpha1 subunit results in a significant increase in
      macroscopic current amplitude. To gain insight into the mechanism underlying this
      interaction, we have examined the regulatory effect of either the alpha2delta
      complex or the delta subunit on the Ca2+ channel alpha1 subunit. Transient
      transfection of tsA201 cells with the cardiac L-type alpha1C subunit alone
      resulted in the expression of inward voltage-activated currents as well as
      measurable [3H]-PN200-110 binding to membranes from transfected cells.
      Coexpression of the alpha2delta subunit significantly increased the macroscopic
      current amplitude, altered the voltage dependence and the kinetics of the
      current, and enhanced [3H]-PN200-110 binding. Except for the increase in
      amplitude, coexpression of the delta subunit reproduced entirely the effects of
      the full-length alpha2delta subunit on the biophysical properties of the alpha1C
      currents. However, no effect on specific [3H]-PN200-110 binding was observed on
      delta subunit coexpression. Likewise, profound effects on current kinetics of the
      neuronal alpha1A subunit were observed on coexpression of the alpha2delta complex
      in Xenopus oocytes. Furthermore, by using a chimeric strategy, we localized the
      region involved in this regulation to the transmembrane domain of the delta
      subunit. These data strongly suggest that the molecular determinants involved in
      alpha2delta regulation are conserved across L-type and non-L type Ca2+ channels.
      Taken together, our results indicate that the region of the alpha2delta subunit
      involved in the modulation of the gating properties of the high voltage-activated
      calcium channels is localized in the delta domain of the protein. In contrast,
      the level of membrane expression of functional channels relies on the presence of
      the alpha2 domain of the alpha2delta complex.

PMID- 9278524
TI  - Studies on the role of fibroblast growth factor signaling in neurogenesis using
      conjugated/aged animal caps and dorsal ectoderm-grafted embryos.
AB  - Basic fibroblast growth factor (bFGF) has been shown to induce neural fate in
      dissociated animal cap (AC) cells or in AC explants cultured in low calcium and
      magnesium concentrations. However, long-term disclosure of the cap may cause
      diffusion of the secreted molecule bone morphogenetic protein 4 (BMP-4), a neural
      inhibitor present in the AC. This may contribute to the subsequent neurogenesis
      induced by bFGF. Here we used conjugated and aged blastula AC to avoid diffusion
      of endogenous molecules from the AC. Unlike noggin, bFGF failed to induce neural
      tissue in this system. However, it enhanced neuralization elicited by a dominant
      negative BMP receptor (DN-BR) that inhibits the BMP-4 signaling. Posterior neural
      markers were turned on by bFGF in AC expressing DN-BR or chordin. Blocking the
      endogenous FGF signal with a dominant negative FGF receptor (XFD) mainly
      inhibited development of posterior neural tissue in neuralized ACs. These in
      vitro studies were confirmed in vivo in embryos grafted with XFD-expressing ACs
      in the place of neuroectoderm. Expression of some regional neural markers was
      inhibited, although markers for muscle and posterior notochord were still
      detectable in the grafted embryos, suggesting that XFD specifically affected
      neurogenesis but not the dorsal mesoderm. The use of these in vitro and in vivo
      model systems provides new evidence that FGF, although unable to initiate
      neurogenesis on its own, is required for neural induction as well as for
      posteriorization.

PMID- 9278525
TI  - The dopamine transporter: comparative ultrastructure of dopaminergic axons in
      limbic and motor compartments of the nucleus accumbens.
AB  - The dopamine transporter (DAT) regulates extracellular dopamine concentrations,
      transports neurotoxins, and acts as a substrate for cocaine reinforcement. These
      functions are known to differ in the limbic-associated shell and motor-associated
      core compartments of the nucleus accumbens (NAc). Previous studies have shown
      differential expression of DAT in the NAc shell and core but were limited in
      resolution to the regional level. Thus, it is not known whether there are
      differences in the amount, subcellular localization, or plasmalemmal targeting of
      DAT within individual dopaminergic axons in the two regions. We used high
      resolution electron microscopic immunocytochemistry to investigate these
      possibilities. We show that in both the shell and core, DAT immunogold labeling
      is present in tyrosine hydroxylase-immunoreactive varicose axons that form
      symmetric synapses. Within these labeled axons, most DAT gold particles are
      located on extrasynaptic plasma membranes, but some are associated with
      intracellular membranes. Dopaminergic axons in the shell contain lower mean
      densities of both total DAT gold particles (per square micron) and plasmalemmal
      DAT gold particles (per micron) than those in the core. Within labeled axons in
      the NAc shell and core, however, there are no detectable differences in the
      subcellullar distribution of DAT or the percentage of total DAT gold particles
      that are located on plasma membranes. These studies are the first to examine and
      compare the subcellular localization of DAT in the NAc shell and core. As a
      result, they identify intrinsic, cell-specific differences in the expression of
      DAT within dopaminergic axons in these functionally distinct striatal
      compartments.

PMID- 9278527
TI  - Regulation of mouse skeletal muscle L-type Ca2+ channel by activation of the
      insulin-like growth factor-1 receptor.
AB  - We investigated the modulation of the skeletal muscle L-type Ca2+
      channel/dihydropyridine receptor in response to insulin-like growth factor-1
      receptor (IGF-1R) activation in single extensor digitorum longus muscle fibers
      from adult C57BL/6 mice. The L-type Ca2+ channel activity in its dual role as a
      voltage sensor and a selective Ca2+-conducting pore was recorded in voltage-clamp
      conditions. Peak Ca2+ current amplitude consistently increased after exposure to
      20 ng/ml IGF-1 (EC50 = 5.6 +/- 1.8 nM). Peak IGF-1 effect on current amplitude at
      -20 mV was 210 +/- 18% of the control. Ca2+ current potentiation resulted from a
      shift in 13 mV of the Ca2+ current-voltage relationship toward more negative
      potentials. The IGF-1-induced facilitation of the Ca2+ current was not associated
      with an effect on charge movement amplitude and/or voltage distribution. These
      phenomena suggest that the L-type Ca2+ channel structures involved in voltage
      sensing are not involved in the response to the growth factor. The modulatory
      effect of IGF-1 on L-type Ca2+ channel was blocked by tyrosine kinase and PKC
      inhibitors, but not by a cAMP-dependent protein kinase inhibitor. IGF-1-dependent
      phosphorylation of the L-type Ca2+ channel alpha1 subunit was demonstrated by
      incorporation of [gamma-32P]ATP to monolayers of adult fast-twitch skeletal
      muscles. IGF-1 induced phosphorylation of a protein at the 165 kDa band,
      corresponding to the L-type Ca2+ channel alpha1 subunit. These results show that
      the activation of the IGF-1R facilitates skeletal muscle L-type Ca2+ channel
      activity via a PKC-dependent phosphorylation mechanism.

PMID- 9278526
TI  - Mechanisms of reduced striatal NMDA excitotoxicity in type I nitric oxide
      synthase knock-out mice.
AB  - We investigated the role of neuronal (type I) nitric oxide synthase (nNOS) in
      NMDA-mediated excitotoxicity in wild-type (SV129 and C57BL/6J) and type I NOS
      knock-out (nNOS-/-) mice and examined its relationship to apoptosis. Excitotoxic
      lesions were produced by intrastriatal stereotactic NMDA microinjections (10-20
      nmol). Lesion size was dose- and time-dependent, completely blocked by MK-801
      pretreatment, and smaller in nNOS knock-out mice compared with wild-type
      littermates (nNOS+/+, 11.7 +/- 1.7 mm3; n = 8; nNOS-/-, 6. 4 +/- 1.8 mm3; n = 7).
      The density and distribution of striatal NMDA binding sites, determined by NMDA
      receptor autoradiography, did not differ between strains. Pharmacological
      inhibition of nNOS by 7-nitroindazole (50 mg/kg, i.p.) decreased NMDA lesion size
      by 32% in wild-type mice (n = 7). Neurochemical and immunohistochemical
      measurements of brain nitrotyrosine, a product of peroxynitrite formation, were
      increased markedly in wild-type but not in the nNOS-/- mice. Moreover, elevations
      in 2,3- and 2,5-dihydroxybenzoic acid levels were significantly reduced in the
      mutant striatum, as a measure of hydroxyl radical production. The importance of
      apoptosis to NMDA receptor-mediated toxicity was evaluated by DNA laddering and
      by quantitative histochemistry [terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) staining]. DNA
      laddering was first detected within lesioned tissue after 12-24 hr. TUNEL
      positive cells were first observed at 12 hr, increased in number at 48 hr and 7
      d, and were located predominantly in proximity to the lesion border. The density
      was significantly lower in nNOS-/- mice. Hence, oligonucleosomal DNA breakdown
      suggesting apoptosis develops as a late consequence of NMDA microinjection and is
      reduced in nNOS mutants. The mechanism of protection in nNOS-/- mice may relate
      to decreased oxygen free radical production and related NO reaction products and,
      in part, involves mechanisms of neuronal death associated with the delayed
      appearance of apoptosis.

PMID- 9278528
TI  - Phosphorylation of the synaptic protein interaction site on N-type calcium
      channels inhibits interactions with SNARE proteins.
AB  - The synaptic protein interaction (synprint) site on the N-type calcium channel
      alpha1B subunit binds to the soluble N-ethylmaleimide-sensitive attachment factor
      receptor (SNARE) proteins syntaxin and synaptosomal protein of 25 kDa (SNAP-25),
      and this association may be required for efficient fast synaptic transmission.
      Protein kinase C (PKC) and calcium and calmodulin-dependent protein kinase type
      II (CaM KII) phosphorylated a recombinant his-tagged synprint site polypeptide
      rapidly to a stoichiometry of 3-4 mol of phosphate/mol, whereas cAMP-dependent
      protein kinase (PKA) and cGMP-dependent protein kinase (PKG) phosphorylated the
      synprint peptide more slowly to a stoichiometry of <1 mol/mol. Two-dimensional
      phosphopeptide mapping revealed similar patterns of phosphorylation of synprint
      polypeptides and native rat brain N-type calcium channel alpha1B subunits by PKC
      and Cam KII. Phosphorylation of the synprint peptide with PKC or CaM KII, but not
      PKA or PKG, strongly inhibited binding of recombinant syntaxin or SNAP-25, even
      at a level of free calcium (15 microM) that stimulates maximal binding. In
      contrast, phosphorylation of syntaxin and SNAP-25 with PKC and CaM KII did not
      affect interactions with the synprint site. Binding assays with polypeptides
      representing the N- and C-terminal halves of the synprint site indicate that the
      PKC- and CaM KII-mediated inhibition of binding involves multiple, disperse
      phosphorylation sites. PKC or CaM KII phosphorylation of the synprint peptide
      also inhibited its interactions with native rat brain SNARE complexes containing
      syntaxin and SNAP-25. These results suggest that phosphorylation of the synprint
      site by PKC or CaM KII may serve as a biochemical switch for interactions between
      N-type calcium channels and SNARE protein complexes.

PMID- 9278529
TI  - Neuroprotective actions of FK506 in experimental stroke: in vivo evidence against
      an antiexcitotoxic mechanism.
AB  - The cellular mechanisms underlying the neuroprotective action of the
      immunosuppressant FK506 in experimental stroke remain uncertain, although in
      vitro studies have implicated an antiexcitotoxic action involving nitric oxide
      and calcineurin. The present in vivo study demonstrates that intraperitoneal
      pretreatment with 1 and 10 mg/kg FK506, doses that reduced the volume of ischemic
      cortical damage by 56-58%, did not decrease excitotoxic damage induced by
      quinolinate, NMDA, and AMPA. Similarly, intravenous FK506 did not reduce the
      volume of striatal quinolinate lesions at a dose (1 mg/kg) that decreased
      ischemic cortical damage by 63%. The temporal window for FK506 neuroprotection
      was defined in studies demonstrating efficacy using intravenous administration at
      120 min, but not 180 min, after middle cerebral artery occlusion. The
      noncompetitive NMDA receptor antagonist MK801 reduced both ischemic and
      excitotoxic damage. Histopathological data concerning striatal quinolinate
      lesions were replicated in neurochemical experiments. MK801, but not FK506,
      attenuated the loss of glutamate decarboxylase and choline acetyltransferase
      activity induced by intrastriatal injection of quinolinate. The contrasting
      efficacy of FK506 in ischemic and excitotoxic lesion models cannot be explained
      by drug pharmacokinetics, because brain FK506 content rose rapidly using both
      treatment protocols and was sustained at a neuroprotective level for 3 d.
      Although these data indicate that an antiexcitotoxic mechanism is unlikely to
      mediate the neuroprotective action of FK506 in focal cerebral ischemia, the
      finding that intravenous cyclosporin A (20 mg/kg) reduced ischemic cortical
      damage is consistent with the proposed role of calcineurin.

PMID- 9278530
TI  - Protein phosphorylation and taurine biosynthesis in vivo and in vitro.
AB  - Taurine is known to be involved in many important physiological functions. Here
      we report that both in vivo and in vitro the taurine-synthesizing enzyme in the
      brain, namely cysteine sulfinic acid decarboxylase (CSAD), is activated when
      phosphorylated and inhibited when dephosphorylated. Furthermore, protein kinase C
      and protein phosphatase 2C have been identified as the enzymes responsible for
      phosphorylation and dephosphorylation of CSAD, respectively. In addition, the
      effect of neuronal depolarization on CSAD activity and 32P incorporation into
      CSAD in neuronal cultures is also included. A model to link neuronal excitation
      and CSAD activation by a Ca2+-dependent protein kinase is proposed.

PMID- 9278531
TI  - Involvement of sphingosine 1-phosphate in nerve growth factor-mediated neuronal
      survival and differentiation.
AB  - Sphingolipid metabolites, such as ceramide and sphingosine-1-phosphate (SPP), are
      emerging as a new class of second messengers involved in cellular proliferation,
      differentiation, and apoptosis. Nerve growth factor (NGF), a neurotrophic factor
      for pheochromocytoma PC12 cells, induced a biphasic increase in the activity of
      sphingosine kinase, the enzyme that catalyzes the formation of SPP. This
      activation was blocked by K252a, an inhibitor of tyrosine kinase A (trkA). A
      rapid 1.7-fold increase was followed by a marked prolonged increase reaching a
      maximum of fourfold to fivefold stimulation with a concomitant increase in SPP
      levels and a corresponding decrease in endogenous sphingosine levels. Levels of
      ceramide, the precursor of sphingosine, were only slightly decreased by NGF in
      serum-containing medium. However, NGF decreased the elevation of ceramide induced
      by serum withdrawal. Treatment of PC12 cells with SPP did not induce neurite
      outgrowth or neurofilament expression, yet it enhanced neurofilament expression
      elicited by suboptimal doses of NGF. Moreover, SPP also protected PC12 cells from
      apoptosis induced by serum withdrawal. To further substantiate a role for SPP in
      the cytoprotective actions of NGF, we found that N, N-dimethylsphingosine, a
      competitive inhibitor of sphingosine kinase, also induced apoptosis and
      interfered with the survival effect of NGF. These effects were counteracted by
      exogenous SPP. Moreover, other structurally related compounds, such as
      dihydrosphingosine 1-phosphate and lysophosphatidic acid, had no significant
      protective effects. Our results suggest that activation of sphingosine kinase and
      subsequent formation of SPP may play an important role in the differentiation and
      survival effects induced by NGF.

PMID- 9278532
TI  - Linearized buffered Ca2+ diffusion in microdomains and its implications for
      calculation of [Ca2+] at the mouth of a calcium channel.
AB  - Immobile and mobile calcium buffers shape the calcium signal close to a channel
      by reducing and localizing the transient calcium increase to physiological
      compartments. In this paper, we focus on the impact of mobile buffers in shaping
      steady-state calcium gradients in the vicinity of an open channel, i.e. within
      its "calcium microdomain." We present a linear approximation of the combined
      reaction-diffusion problem, which can be solved explicitly and accounts for an
      arbitrary number of calcium buffers, either endogenous or added exogenously. It
      is valid for small saturation levels of the present buffers and shows that within
      a few hundred nanometers from the channel, standing calcium gradients develop in
      hundreds of microseconds after channel opening. It is shown that every buffer can
      be assigned a uniquely defined length-constant as a measure of its capability to
      buffer calcium close to the channel. The length-constant clarifies intuitively
      the significance of buffer binding and unbinding kinetics for understanding local
      calcium signals. Hence, we examine the parameters shaping these steady-state
      gradients. The model can be used to check the expected influence of single
      channel calcium microdomains on physiological processes such as excitation
      secretion coupling or excitation-contraction coupling and to explore the
      differential effect of kinetic buffer parameters on the shape of these
      microdomains.

PMID- 9278533
TI  - Selective expression of insulin-like growth factor II in the songbird brain.
AB  - Neuronal replacement occurs in the forebrain of juvenile and adult songbirds. To
      address the molecular processes that govern this replacement, we cloned the zebra
      finch insulin-like growth factor II (IGF-II) cDNA, a factor known to regulate
      neuronal development and survival in other systems, and examined its expression
      pattern by in situ hybridization and immunocytochemistry in juvenile and adult
      songbird brains. The highest levels of IGF-II mRNA expression occurred in three
      nuclei of the song system: in the high vocal center (HVC), in the medial
      magnocellular nucleus of the neostriatum (mMAN), which projects to HVC, and to a
      lesser extent in the robust nucleus of the archistriatum (RA), which receives
      projections from HVC. IGF-II mRNA expression was developmentally regulated in
      zebra finches. In canary HVC, monthly changes in IGF-II mRNA expression covaried
      with previously reported monthly differences in neuron incorporation. Combining
      retrograde tracers with in situ hybridization and immunocytochemistry, we
      determined that the HVC neurons that project to area X synthesize the IGF-II
      mRNA, whereas the adjacent RA-projecting neurons accumulate the IGF-II peptide.
      Our findings raise the possibility that within HVC IGF-II acts as a paracrine
      signal between nonreplaceable area X-projecting neurons and replaceable RA
      projecting neurons, a mode of action that is compatible with the involvement of
      IGF-II with the replacement of neurons. Additional roles for IGF-II expression in
      songbird brain are likely, because expression also occurs in some brain areas
      outside the song system, among them the cerebellar Purkinje cells in which
      neurogenesis is not known to occur.

PMID- 9278534
TI  - Transgenic mice expressing the intracellular domain of the p75 neurotrophin
      receptor undergo neuronal apoptosis.
AB  - We have asked whether p75(NTR) may play a role in neuronal apoptosis by producing
      transgenic mice that express the p75(NTR) intracellular domain within peripheral
      and central neurons. These animals showed profound reductions in numbers of
      sympathetic and peripheral sensory neurons as well as cell loss in the neocortex,
      where there is normally little or no p75(NTR) expression. Developmental loss of
      facial motor neurons was not observed, but induced expression of the p75(NTR)
      intracellular domain within adult animals led to increased motor neuron death
      after axotomy. Biochemical analyses suggest that these effects were not
      attributable to a p75(NTR)-dependent reduction in trk activation but instead
      indicate that the p75(NTR) intracellular domain may act as a constitutive
      activator of signaling cascades that regulate apoptosis in both peripheral and
      central neurons.

PMID- 9278535
TI  - Endogenous ciliary neurotrophic factor is a lesion factor for axotomized
      motoneurons in adult mice.
AB  - Ciliary neurotrophic factor (CNTF) is an abundant cytosolic molecule in
      myelinating Schwann cells of adult rodents. In newborn animals in which CNTF is
      not yet expressed, exogenous CNTF that is locally administered very effectively
      protects motoneurons from degeneration by axotomy. To evaluate whether endogenous
      CNTF, released after nerve injury from the cytosol of Schwann cells, supports
      motoneuron survival, we transected the facial nerve in 4-week-old pmn mice. In
      this mouse mutant a rapidly progressing degenerative disease of motoneurons
      starts by the third postnatal week at the hindlimbs and progresses to the
      anterior parts of the body, leading to death by the seventh to eighth week.
      Apoptotic death of motoneurons can be observed during this period, as revealed by
      TUNEL staining. In 6-week-old unlesioned pmn mice approximately 40% of facial
      motoneurons have degenerated. Facial nerve lesion dramatically increased the
      number of surviving motoneurons in pmn mice. This protective effect was absent in
      pmn mice lacking endogenous CNTF. Quantitative analysis of leukemia inhibitory
      factor (LIF) mRNA expression revealed that the dramatic upregulation seen in wild
      type mice after peripheral nerve lesion did not occur in pmn mice. Therefore,
      endogenous LIF cannot compensate for the lack of CNTF in pmn crossbred with CNTF
      knock-out mice. Thus, endogenous CNTF released from lesioned Schwann cells
      supports the survival of axotomized motoneurons under conditions in which
      motoneurons are in the process of rapid degeneration.

PMID- 9278536
TI  - Trk receptors function as rapid retrograde signal carriers in the adult nervous
      system.
AB  - During development target-derived neurotrophins promote the survival of neurons.
      However, mature neurons no longer depend on the target for survival. Do target
      derived neurotrophins retain retrograde signaling functions in mature neurons,
      and, if so, how are they executed? We addressed this question by using a
      phosphotyrosine-directed antibody to locate activated Trk receptors in adult rat
      sciatic nerve. We show that catalytically active Trk receptors are located within
      the axon of adult rat sciatic nerve and that they are distributed throughout the
      length of the axons. These catalytically active receptors are phosphorylated on
      tyrosine at a position that couples them to the signal-generating proteins Ras
      and PI3 kinase. Neurotrophin applied at sciatic nerve terminals increases both
      catalytic activity and phosphorylation state of Trk receptors at distant points
      within the axons. Trk activation initiated at the nerve terminals propagates
      through the axon toward the nerve cell body at an initial rate that exceeds that
      of conventional vesicular transport. However, our data suggest that this rapid
      signal is nevertheless vesicle-associated. Thus, in mature nerves, activated Trk
      receptors function as rapid retrograde signal carriers to execute remote
      responses to target-derived neurotrophins.

PMID- 9278537
TI  - A postsynaptic excitatory amino acid transporter with chloride conductance
      functionally regulated by neuronal activity in cerebellar Purkinje cells.
AB  - Excitatory amino acid (EAA) neurotransmitters induce postsynaptic depolarization
      by activating receptor-mediated cation conductances, a process known to underlie
      changes in synaptic efficacy. Using a patch-clamp method, we demonstrate here an
      EAA-dependent postsynaptic anion conductance mediated by EAA transporters present
      on cerebellar Purkinje cell bodies and dendrites in culture. This transporter
      mediated current was modulated by neuronal activity: it exhibited facilitation
      for >20 min after transient depolarization accompanied by Ca2+ influx. Evidence
      is presented suggesting that the transporter facilitation is mediated by
      arachidonate release after Ca2+-dependent activation of phospholipase A2, which
      exists in Purkinje cells. This postsynaptic reuptake system may represent a novel
      modulatory mechanism of synaptic transmission as well as prevent neuronal
      excitotoxicity.

PMID- 9278538
TI  - Morphogenesis of the node of Ranvier: co-clusters of ankyrin and ankyrin-binding
      integral proteins define early developmental intermediates.
AB  - AnkyrinG 480/270 kDa and three ankyrin-binding integral membrane proteins
      (neurofascin, NrCAM, and the voltage-dependent sodium channel) colocalize within
      a specialized domain of the spectrin-actin network found at axonal segments of
      nodes of Ranvier in myelinated axons. Before myelination in embryonic nerves,
      ankyrinG 480/270 kDa and the related ankyrin isoform ankyrinB 440 kDa are co
      expressed along with NrCAM in an abundant, continuous distribution along the
      length of axons. This study has resolved intermediate stages in the developmental
      transition from a continuous distribution of ankyrinG 480/270 kDa in all axons to
      a highly polarized localization at the node of Ranvier in the developing rat
      sciatic nerve. The first detected event is formation of clusters containing the
      cell adhesion molecules neurofascin and NrCAM at sites independent of myelin
      associated glycoprotein (MAG)-staining Schwann cell processes. Subsequent steps
      involve recruitment of ankyrinG 480/270 kDa and the voltage-dependent sodium
      channel to cluster sites containing cell adhesion molecules, and elaboration of
      MAG-staining Schwann cell processes adjacent to these cluster sites. Formation of
      the mature node of Ranvier results from the fusion of asynchronously formed pairs
      of clusters associated with MAG-positive Schwann cells flanking the site of
      presumed node formation. Studies with the hypomyelinating mutant mouse trembler
      demonstrate that the elaboration of compact myelin is not required for the
      formation of these clustered nodal intermediates. Clustering of neurofascin and
      NrCAM precedes redistribution of ankyrinG 480/270 kDa and the voltage-dependent
      sodium channel, suggesting that the adhesion molecules define the initial site
      for subsequent assembly of ankyrin and the voltage-dependent sodium channel.

PMID- 9278539
TI  - Cell coupling and uncoupling in the ventricular zone of developing neocortex.
AB  - Cells within the ventricular zone (VZ) of developing neocortex are coupled
      together into clusters by gap junction channels. The specific role of clustering
      in cortical neurogenesis is unknown; however, clustering provides a means for
      spatially restricted local interactions between subsets of precursors and other
      cells within the VZ. In the present study, we have used a combination of 5-bromo
      2'-deoxyuridine (BrDU) pulse labeling, intracellular biocytin labeling, and
      immunocytochemistry to determine when in the cell cycle VZ cells couple and
      uncouple from clusters and to determine what cell types within the VZ are coupled
      to clusters. Our results indicate that clusters contain radial glia and neural
      precursors but do not contain differentiating or migrating neurons. In early
      neurogenesis, all precursors in S and G2 phases of the cell cycle are coupled,
      and approximately half of the cells in G1 are coupled. In late neurogenesis,
      however, over half of the cells in both G1 and S phases are not coupled to VZ
      clusters, whereas all cells in G2 are coupled to clusters. Increased uncoupling
      in S phase during late neurogenesis may contribute to the greater percentage of
      VZ cells exiting the cell cycle at this time. Consistent with this hypothesis, we
      found that pharmacologically uncoupling VZ cells with octanol decreases the
      percentage of VZ cells that enter S phase. These results demonstrate that cell
      clustering in the VZ is restricted to neural precursors and radial glia, is
      dynamic through the cell cycle, and may play a role in regulating neurogenesis.

PMID- 9278540
TI  - Axonal transport blockade in the neonatal rat optic nerve induces limited retinal
      ganglion cell death.
AB  - Optic nerve section in the newborn rat results in a rapid apoptotic degeneration
      of most axotomized retinal ganglion cells (RGCs). This massive process of
      neuronal death has been ascribed mainly to the interruption of a trophic factor
      supply from target structures rather than to the axonal damage per se. To
      distinguish between these two possibilities, we induced a reversible axonal
      transport blockade in the developing optic nerve by topical application of a
      local anesthetic (lidocaine). Light and electron microscopy showed no alterations
      in the fine structure of treated optic nerves. Retinae of treated and control
      rats were stained with cresyl violet and examined at different times after
      surgery. We found that axonal transport blockade induced only a limited number of
      pyknotic RGCs. Degeneration of these cells was completely prevented by inhibiting
      protein synthesis during lidocaine application. We conclude that the rapid
      degeneration of RGCs after axotomy can be ascribed only partly to the loss of
      retrogradely transported trophic factors.

PMID- 9278541
TI  - Abeta deposition is associated with neuropil changes, but not with overt neuronal
      loss in the human amyloid precursor protein V717F (PDAPP) transgenic mouse.
AB  - The PDAPP transgenic mouse overexpresses human amyloid precursor protein V717F
      (PDAPP minigene) and develops age-related cerebral amyloid-beta protein (Abeta)
      deposits similar to senile plaques in Alzheimer's disease. We find age-related
      cortical and limbic Abeta deposition that begins at 8 months and progresses to
      cover 20-50% of the neuropil in cingulate cortex, entorhinal cortex, and
      hippocampus of 18-month-old heterozygotic animals. The regional patterns of
      transgene expression and amyloid deposition suggest that Abeta deposits occur at
      the terminals of overexpressing neurons. Amyloid deposition is associated with
      dystrophic neurites and extensive gliosis. However, stereological analysis shows
      that there is no overt neuronal loss in entorhinal cortex, CA1 hippocampal
      subfield, or cingulate cortex through 18 months of age. In addition, there is no
      apparent loss of mRNA encoding neuronal synaptic, cytoskeletal, or metabolic
      proteins. Thus, widespread Abeta deposition in 18-month-old heterozygotic mice
      produces neuritic alterations and gliosis without widespread neuronal death.

PMID- 9278542
TI  - Functional analysis of V3A and related areas in human visual cortex.
AB  - Using functional magnetic resonance imaging (fMRI) and cortical unfolding
      techniques, we analyzed the retinotopy, motion sensitivity, and functional
      organization of human area V3A. These data were compared with data from
      additional human cortical visual areas, including V1, V2, V3/VP, V4v, and MT
      (V5). Human V3A has a retinotopy that is similar to that reported previously in
      macaque: (1) it has a distinctive, continuous map of the contralateral hemifield
      immediately anterior to area V3, including a unique retinotopic representation of
      the upper visual field in superior occipital cortex; (2) in some cases the V3A
      foveal representation is displaced from and superior to the confluent foveal
      representations of V1, V2, V3, and VP; and (3) inferred receptive fields are
      significantly larger in human V3A, compared with those in more posterior areas
      such as V1. However, in other aspects human V3A appears quite different from its
      macaque counterpart: human V3A is relatively motion-selective, whereas human V3
      is less so. In macaque, the situation is qualitatively reversed: V3 is reported
      to be prominently motion-selective, whereas V3A is less so. As in human and
      macaque MT, the contrast sensitivity appears quite high in human areas V3 and
      V3A.

PMID- 9278543
TI  - Structural and functional analyses of human cerebral cortex using a surface-based
      atlas.
AB  - We have analyzed the geometry, geography, and functional organization of human
      cerebral cortex using surface reconstructions and cortical flat maps of the left
      and right hemispheres generated from a digital atlas (the Visible Man). The total
      surface area of the reconstructed Visible Man neocortex is 1570 cm2 (both
      hemispheres), approximately 70% of which is buried in sulci. By linking the
      Visible Man cerebrum to the Talairach stereotaxic coordinate space, the locations
      of activation foci reported in neuroimaging studies can be readily visualized in
      relation to the cortical surface. The associated spatial uncertainty was
      empirically shown to have a radius in three dimensions of approximately 10 mm.
      Application of this approach to studies of visual cortex reveals the overall
      patterns of activation associated with different aspects of visual function and
      the relationship of these patterns to topographically organized visual areas. Our
      analysis supports a distinction between an anterior region in ventral occipito
      temporal cortex that is selectively involved in form processing and a more
      posterior region (in or near areas VP and V4v) involved in both form and color
      processing. Foci associated with motion processing are mainly concentrated in a
      region along the occipito-temporal junction, the ventral portion of which
      overlaps with foci also implicated in form processing. Comparisons between flat
      maps of human and macaque monkey cerebral cortex indicate significant differences
      as well as many similarities in the relative sizes and positions of cortical
      regions known or suspected to be homologous in the two species.

PMID- 9278544
TI  - Recalling routes around london: activation of the right hippocampus in taxi
      drivers.
AB  - Functional imaging to date has examined the neural basis of knowledge of spatial
      layouts of large-scale environments typically in the context of episodic memory
      with specific spatiotemporal references. Much human behavior, however, takes
      place in very familiar environments in which knowledge of spatial layouts has
      entered the domain of general facts often referred to as semantic memory. In this
      study, positron emission tomography (PET) was used to examine the neural
      substrates of topographical memory retrieval in licensed London taxi drivers of
      many years experience while they recalled complex routes around the city.
      Compared with baseline and other nontopographical memory tasks, this resulted in
      activation of a network of brain regions, including the right hippocampus. Recall
      of famous landmarks for which subjects had no knowledge of their location within
      a spatial framework activated similar regions, except for the right hippocampus.
      This suggests that the hippocampus is involved in the processing of spatial
      layouts established over long time courses. The involvement of similar brain
      areas in routes and landmarks memory indicates that the topographical memory
      system may be primed to respond to any relevant topographical stimulation;
      however, the right hippocampus is recruited specifically for navigation in large
      scale spatial environments. In contrast, nontopographical semantic memory
      retrieval involved the left inferior frontal gyrus, with no change in activity in
      medial temporal regions.

PMID- 9278545
TI  - GDNF protection against 6-OHDA: time dependence and requirement for protein
      synthesis.
AB  - Glial cell line-derived neurotrophic factor (GDNF) injected intranigrally
      protects midbrain dopamine neurons against 6-hydroxydopamine (6-OHDA) toxicity.
      The timing between GDNF administration and exposure to 6-OHDA is critical in
      achieving optimal protection. When injected 6 hr before an intranigral injection
      of 6-OHDA, GDNF provides complete protection as measured by the number of
      surviving neurons in the substantia nigra of adult rats. The surviving neuronal
      population decreases by approximately 50% with 12 and 24 hr separating GDNF and 6
      OHDA administrations. In controls with 6-OHDA lesions, there is <10% survival of
      nigral dopamine neurons. No significant increase in survival is seen with either
      concurrent injections of GDNF and 6-OHDA or 1 hr GDNF pretreatment. Based on HPLC
      measurements, striatal and midbrain dopamine levels are at least twofold higher
      on the lesioned side in animals receiving GDNF 6 hr before a 6-OHDA lesion
      compared with vehicle recipients. Protein synthesis is necessary for GDNF-induced
      neuroprotective effects because cycloheximide pretreatment that inhibits protein
      synthesis also blocks neuroprotection.

PMID- 9278546
TI  - Obstacle avoidance and a perturbation sensitivity model for motor planning.
AB  - A novel obstacle avoidance paradigm was used to investigate the planning of human
      reaching movements. We explored whether the CNS plans arm movements based
      entirely on the visual space kinematics of the movements, or whether the planning
      process incorporates specific details of the biomechanical plant to optimize the
      trajectory plan. Participants reached around an obstacle, the tip of which
      remained fixed in space throughout the experiment. When the obstacle and the
      start and target locations were rotated about the tip of the obstacle, the
      visually specified task constraints retained a rotational symmetry. If movements
      are planned in visual space, as indicated from a variety of studies on planar
      point-to-point movements, the resulting trajectories should also be rotationally
      symmetric across trials. However, systematic variations in movement path were
      observed as the orientation of the obstacle was changed. These path asymmetries
      can be accounted for by a class of models in which the planner reduces the
      likelihood of collision with the obstacle by taking into account the anisotropic
      sensitivity of the arm to external perturbations or uncertainty in joint level
      control or proprioception. The model that best matches the experimental results
      uses planning criteria based on the inertial properties of the arm.

PMID- 9278547
TI  - A polysynaptic feedback circuit in rat visual cortex.
AB  - Feedback connections from extrastriate cortex to primary visual cortex (V1) in
      the primate may provide "top-down" information that plays a role in visual
      attention and object recognition. Our work in a rodent model of corticocortical
      circuitry demonstrates that feedback pathways synapse preferentially with
      pyramidal cells in V1 () and favor excitation over inhibition in cortical
      microcircuits (). To investigate the polysynaptic circuits activated by feedback
      inputs, we studied chains of neurons postsynaptic to feedback connections using a
      combination of axonal tract tracing and anterograde degeneration. This approach
      enabled independent labeling of local collaterals of forward-projecting neurons
      in V1 and feedback connections from extrastriate lateromedial (LM) visual area to
      V1. Postsynaptic targets were identified in the electron microscope after
      retrograde transport of biotinylated dextran amine (BDA) to identify dendrites of
      forward-projecting neurons (i.e., from V1 to LM) and postembedding immunogold
      labeling to identify GABAergic interneurons. The results show that feedback
      connections provide strong monosynaptic input to forward-projecting neurons in
      V1. These neurons in turn make local connections that preferentially form
      synapses with other pyramidal cells ( approximately 97%), many of which were
      identified as forward-projecting neurons. This indicates that feedback pathways
      provide input directly to neurons which make the reciprocal forward connection,
      and that feedback-recipient forward-projecting neurons are strongly
      interconnected. The function of these excitatory networks within V1 may be to
      amplify feedback activity and provide a circuit for modulation of striate
      cortical activity by top-down influences.

PMID- 9278548
TI  - Modulation of the parieto-occipital alpha rhythm during object detection.
AB  - Changes in the human neuromagnetic alpha rhythm were monitored during an object
      detection task to study the effects of visual shape processing on the parieto
      occipital activity. Pictures of coherent meaningful objects, which the observers
      had to detect, and of disorganized meaningless non-objects were presented briefly
      between masks. The non-objects were systematically followed by a higher level of
      alpha than the objects, the difference emerging on average 400 msec after the
      stimulus, with a median delay of 130 msec after evoked response onsets in the
      occipital, temporal, and parietal cortices. Without attention to visual shape,
      the alpha levels did not differ between objects and non-objects. The alpha level
      was higher after non-objects than missed objects, and higher after missed than
      correctly detected objects, suggesting that the alpha level is inversely related
      to saliency or familiarity of the object and does not directly reflect visual
      awareness. The reactive alpha rhythm was generated in the parieto-occipital
      sulcus, which in several primate species includes areas belonging to the dorsal
      visual pathway. According to current views, the parietal cortex produces
      attentional signals that filter out irrelevant information in the ventral visual
      stream. Our results reinforce the idea of bidirectional interaction: information
      derived from visual shape can rapidly modify activity in the parieto-occipital
      region. The synchronized alpha oscillations may reflect attenuation of occipito
      parietal information transfer and disengagement of parietal cortex from object
      selection.

PMID- 9278549
TI  - Activity-dependent changes to the brain and behavior of the honey bee, Apis
      mellifera (L.).
AB  - To explore the origins and possible behavioral consequences of structural
      plasticity in an insect brain, we have taken advantage of the following: (1) the
      highly compartmentalized nature of the primary antenno-sensory centers (antennal
      lobes) of the brain, (2) the ease with which individual compartments, or
      glomeruli, within the antennal-lobe neuropil can be identified, and (3) the
      predictability of changes to readily identifiable glomeruli in the antennal lobes
      of the adult worker honey bee. Treatment with the juvenile hormone analog
      methoprene and hive manipulation techniques are used to induce precocious
      foraging behavior in young worker honey bees. The impact of these treatments on
      the ontogeny of olfactory learning performance and on the volumes of readily
      identifiable glomeruli in the antennal lobes of the bee brain are examined in
      parallel. The study reveals that (1) significant changes in glomerular volume are
      activity dependent and (2) associative learning of floral odors improves with
      experience. Improvements in associative learning performance coincide temporally
      with increases in glomerular volume. This raises an important question: are
      changes in glomerular volume that result from shifts in behavior simply a
      consequence of changes in the use of peripheral sensory pathways, or are they
      associated with events that underlie learning and the formation of long-term
      memories?

PMID- 9278550
TI  - The alpha2a adrenergic receptor subtype mediates spinal analgesia evoked by
      alpha2 agonists and is necessary for spinal adrenergic-opioid synergy.
AB  - Agonists acting at alpha2 adrenergic and opioid receptors have analgesic
      properties and act synergistically when co-administered in the spinal cord; this
      synergy may also contribute to the potency and efficacy of spinally administered
      morphine. The lack of subtype-selective pharmacological agents has previously
      impeded the definition of the adrenergic receptor subtype(s) mediating these
      effects. We therefore exploited a genetically modified mouse line expressing a
      point mutation (D79N) in the alpha2a adrenergic receptor (alpha2aAR) to
      investigate the role of the alpha2aAR in alpha2 agonist-evoked analgesia and
      adrenergic-opioid synergy. In the tail-flick test, intrathecal administration of
      UK 14,304, a nonsubtype-selective alpha2AR agonist, had no analgesic effect in
      D79N mice, whereas the analgesic potency of morphine (intrathecal) in this assay
      was not affected by the mutation. The mutation also decreased alpha2-agonist
      mediated spinal analgesia and blocked the synergy seen in wild-type mice with
      both the delta-opioid agonist deltorphin II and the micro-opioid agonist [D
      ALA2,N-Me-Phe4, Gly-ol5]-Enkephalin (DAMGO) in the substance P behavioral test.
      In addition, the potency of spinally administered morphine was decreased in this
      test, suggesting that activation of descending noradrenergic systems impinging on
      the alpha2aAR contributes to morphine-induced spinal inhibition in this model.
      These results demonstrate that the alpha2aAR subtype is the primary mediator of
      alpha2 adrenergic spinal analgesia and is necessary for analgesic synergy with
      opioids. Thus, combination therapies targeting the alpha2aAR and opioid receptors
      may prove useful in maximizing the analgesic efficacy of opioids while decreasing
      total dose requirements.

PMID- 9278552
TI  - Induction of nitric oxide synthase in rat intestine by interleukin-1alpha may
      explain diarrhea associated with zinc deficiency.
AB  - Synthesis of inducible nitric oxide synthase (iNOS) in the intestine may result
      in local tissue damage. We investigated whether a challenge with interleukin
      1alpha could give rise to intestinal iNOS expression and diarrhea in rats of
      differing zinc status. Weaning male rats were fed a zinc-deficient (ZD) diet (2
      mg zinc/kg) for 4 wk to induce zinc deficiency or a zinc-supplemented diet [50.8
      mg zinc/kg; controls, including pair-fed (PF ) and ad libitum (AL) consumption
      groups], and then subcutaneously injected with interleukin-1alpha (2 x 10(7)
      units/kg body wt). Without the interleukin-1alpha challenge, ZD rats had
      significantly lower plasma zinc concentration than the other groups. Intestinal
      metallothionein-1 mRNA abundance was lower in ZD rats than in AL rats. iNOS was
      expressed in the intestine of ZD rats but not in the others. None of the rats
      experienced diarrhea during the feeding period. Interleukin-1alpha led to a
      reduction in plasma zinc concentration, enhancement in intestinal metallothionein
      1 mRNA levels, and expression of the intestinal iNOS gene in all groups. However,
      the abundance of iNOS mRNA was significantly higher in ZD rats than in the other
      groups. The presence of iNOS protein was demonstrated by immunohistochemical
      staining in the intestine of ZD rats that had been treated with interleukin
      1alpha 12 h earlier. In addition, diarrhea occurred in most of the ZD rats and
      some of the PF rats but not in AL rats after interleukin-1alpha treatment. We
      conclude that ZD rats respond to interleukin-1alpha challenge more severely than
      controls, reflected by a more marked and prolonged iNOS expression and a greater
      incidence of diarrhea.

PMID- 9278551
TI  - Evidence for an intramedullary prostaglandin-dependent mechanism in the
      activation of stress-related neuroendocrine circuitry by intravenous interleukin
      1.
AB  - We have provided evidence that the stimulatory effects of intravenous interleukin
      1 (IL-1) on neurosecretory neurons in the paraventricular nucleus (PVH) that
      express corticotropin-releasing factor (CRF) depend specifically on the integrity
      of catecholaminergic projections originating in caudal medulla. Here we report on
      experiments designed to test alternative means by which circulating IL-1 might
      access medullary aminergic neurons, including mechanisms involving sensory
      components of the vagus, the area postrema, or perivascular cells bearing IL-1
      receptors. Neither abdominal vagotomy nor area postrema lesions reliably altered
      Fos expression induced in the medulla or PVH in response to a moderately
      suprathreshold dose of IL-1beta. Cytokine-stimulated increases in CRF mRNA in the
      PVH were also unaffected by either ablation. By contrast, systemic administration
      of the cyclooxygenase inhibitor indomethacin resulted in parallel dose-related
      attenuations of IL-1 effects in hypothalamus and medulla. Microinjections of
      prostaglandin E2 (PGE2; >/=10 ng) in rostral ventrolateral medulla, the principal
      seat of IL-1-sensitive neurons that project to the PVH, provoked discrete
      patterns of cellular activation in hypothalamus and medulla that mimicked those
      seen in response to intravenous IL-1. We interpret these findings as supporting
      the hypothesis that paracrine effects of PGE2 released from perivascular cells in
      the medulla as a consequence of IL-1 stimulation and, acting through prostanoid
      receptors on or near local aminergic neurons that project to the PVH, contribute
      to the stimulatory effects of increased circulating IL-1 on neurons constituting
      the central limb of the hypothalamo-pituitary-adrenal axis.

PMID- 9278553
TI  - Lactase decline in weaning rats is regulated at the transcriptional level and not
      caused by termination of milk ingestion.
AB  - Lactase activity declines during postnatal development in rats, but little is
      known about the underlying molecular mechanism of this phenomenon. We attempted
      to clarify whether the regulation was at the transcriptional or post
      transcriptional level and to examine the effects of dietary factors on that
      regulation. Newborn rats were divided into two groups, prolonged nursing and
      weaning, at d 21. The prolonged nursing rats were nursed for a further 6 d,
      whereas weaning rats were separated from their dams and fed nonpurified diet for
      the same period. The patterns of declining lactase protein and mRNA
      concentrations during weaning were determined by Western blot and Northern blot
      analyses, respectively, and compared with lactase activity. There were
      significant (P < 0.001) correlations between them: r = 0.97 for specific activity
      vs. protein, r = 0.99 for specific activity vs. mRNA and r = 0.96 for protein vs.
      mRNA. The lactase activity per milligram DNA showed a pattern similar to that of
      the specific activity. This result argues against the decline in lactase activity
      being due to the dilution caused by newly synthesized materials during the
      weaning period and suggests transcriptional regulation. Furthermore, the
      prolonged nursing rats showed the same results as weanlings for lactase protein,
      mRNA, specific activity and activity per milligram DNA. These observations
      indicate that the regulation of lactase expression is at the transcriptional
      level and that it is not affected by the termination of milk ingestion.

PMID- 9278554
TI  - Partially purified soy hydrolysates retard proliferation and inhibit bacterial
      translocation in cultured C2BBe cells.
AB  - Hydrolyzed soybean isolates SP-A and SP-B (Abbott Laboratories, OH), developed
      for use in enteral nutritional products, were tested in cultures of C2BBe cells,
      a colonic adenocarcinoma cell line with enterocytic differentiation, to evaluate
      effects on cell growth, maturation and ability to resist infection by enteric
      bacteria. SP-A delayed formation of confluent monolayers by 10 d compared with
      cells cultured without SP-A. SP-A also caused a retardation in the development of
      intercellular tight junctions as measured by transmonolayer electrical resistance
      (TER). SP-B had no effect on cell proliferation or TER of intestinal cell
      cultures. SP-A and SP-B enhanced the development of the brush border enzymes
      alkaline phosphatase and isomaltase over a 28 d period. By these criteria, SP-A
      and SP-B appear to affect intestinal epithelial cell development in culture. When
      C2BBe monolayers were exposed to the enteric bacteria, Salmonella typhimurium or
      Salmonella typhi, an inhibition of the passage of S. typhi was seen in cultures
      with SP-A and SP-B. No effect on the passage of S. typhimurium was seen with
      either soy isolate. Partially purified soy isolates therefore impart resistance
      to selected enteroinvasive bacteria. Addition of soy hydrolysates to the media of
      cultured intestinal cells may serve as a rapid and economical screening mechanism
      for preclinical trials that would test the therapeutic benefits of soybean
      isolates.

PMID- 9278555
TI  - Perilla oil prevents the excessive growth of visceral adipose tissue in rats by
      down-regulating adipocyte differentiation.
AB  - We examined the effect of dietary oils with different fatty acid compositions on
      the growth of visceral adipose tissue in rats. Rats were fed for 4 mo starting at
      weaning a basal diet containing (12 g/100 g diet) perilla oil rich in (n-3)
      polyunsaturated fatty acids (PUFA), safflower oil rich in (n-6) PUFA, olive oil
      rich in monounsaturated fatty acid, or beef tallow rich in saturated fatty acids.
      The amount of food consumed and body weight gain did not differ among the four
      dietary groups. The weight of the epididymal fat pad and the serum triglyceride
      concentration in perilla oil-fed rats were significantly lower (P < 0.05) than
      those of olive oil- and beef tallow-fed groups. The product of [(volume of
      individual adipocytes) x (number of adipocytes in epididymal fat pad)], which
      presumably represents total adipocyte volume in the fat pad, was significantly
      lower (P < 0.05) in perilla oil-fed rats than in beef tallow- and olive oil-fed
      groups. Expression of the late genes of adipocyte differentiation, peroxisome
      proliferator-activated receptor alpha, adipocyte P2 and adipsin, was
      significantly (P < 0. 05) down-regulated in epididymal fat tissue of rats that
      had been fed perilla oil rather than beef tallow or olive oil, whereas expression
      of the early gene, lipoprotein lipase, was not significantly affected. Greater
      levels (P < 0.05) of (n-3) PUFA in the membrane phospholipid fraction of the fat
      tissue were observed in perilla oil-fed rats than in the other dietary groups.
      These results suggest that perilla oil or (n-3) PUFA prevents excessive growth of
      adipose tissue in rats at least in part by suppressing the late phase of
      adipocyte differentiation.

PMID- 9278556
TI  - Dietary energy tissue-specifically regulates endoplasmic reticulum chaperone gene
      expression in the liver of mice.
AB  - A number of putative molecular chaperones seem to play essential roles in the
      correct folding, assembly and glycosylation of membrane and secreted proteins in
      the endoplasmic reticulum. We have shown that life span-extending dietary energy
      restriction significantly and specifically reduces GRP78 mRNA and protein by 50
      75% in mice. Here, 5-mo-old female C3B10RF1 mice were given free access to food
      after being fed 50% less dietary energy since weaning. Hepatic GRP78 mRNA
      increased linearly, reaching the same level after 2 wk as was found in the liver
      of 20-mo-old mice with free access to food. This increase took place with no
      change in body weight. The mRNA levels of endoplasmic reticulum, cytosolic and
      mitochondrial chaperones were determined in young (7-mo-old) and old (21- or 28
      mo-old) female C3B10RF1 mice. Each age group was either 50% energy restricted or
      was fed approximately 10% less energy than consumed by mice given free access to
      food. In young and old energy-restricted mice, hepatic expression of the
      endoplasmic reticulum chaperones ERp57 (37%), GRP170 (51%), ERp72 (43%),
      calreticulin (54%) and calnexin (23%) was significantly and specifically reduced.
      The GRP78, GRP94, GRP170, ERp57 and calnexin mRNA response to diet occurred
      reproducibly only in liver, and not in adipose, brain, heart, kidney, lung,
      muscle or small intestine. The mRNA for GRP75, a mitochondrial chaperone, HSC70,
      a cytoplasmic chaperone, protein disulfide isomerase, an endoplasmic reticulum
      chaperone, and C/EBPalpha, a transcription factor, was not regulated. Hepatic
      C/EBPbeta was 15% higher in old energy-restricted mice. Thus the expression of
      nearly all endoplasmic reticulum chaperones responded rapidly and specifically to
      dietary energy in mice.

PMID- 9278557
TI  - Dietary gamma-linolenic acid enhances mouse macrophage-derived prostaglandin E1
      which inhibits vascular smooth muscle cell proliferation.
AB  - We previously demonstrated that macrophages isolated from mice fed gamma
      linolenic acid (GLA)-enriched diets reduce vascular smooth muscle cell (SMC)
      proliferation in a cyclooxygenase-dependent fashion and may therefore favorably
      modulate the atherogenic process. The present study was conducted to elucidate
      the mechanism(s) by which dietary GLA influences the ability of macrophages to
      modulate SMC growth programs. Resident peritoneal macrophages were isolated from
      C57BL/6 female mice fed diets containing variable GLA compositions at 10%
      (wt/wt), treated with various antibodies and co-cultured with cycling naive
      vascular SMC isolated from nonpurified diet-fed mice. Smooth muscle cell
      proliferation and intracellular cAMP levels were measured after co-culture. In
      parallel experiments, cycling naive vascular SMC isolated from nonpurified diet
      fed mice were dosed with exogenous prostaglandin E1 (PGE1 ) for various periods
      and challenged with cycloheximide for 4 h (8-12 h after PGE1 addition), and
      intracellular cAMP levels were measured at various time points. Macrophages
      isolated from mice fed GLA-enriched dietary oils significantly reduced SMC
      proliferation in co-culture compared with controls (macrophages from mice fed a
      corn oil diet containing no GLA). Anti-PGE1 antiserum treatment (1:50 or 1:100)
      blocked the ability of GLA-enriched macrophages to down-regulate SMC
      proliferation, a response reversed by exogenous PGE1 treatment. Macrophages
      isolated from mice fed GLA-enriched dietary oils elevated SMC intracellular cAMP
      levels in a biphasic fashion. In addition, exogenous PGE1 (1 nmol/L to 10
      micromol/L) exerted a similar biphasic cAMP response in SMC, and the second phase
      of cAMP elevation was antagonized by cycloheximide. In conclusion, dietary GLA
      enhances mouse macrophage-derived prostaglandin E1, which inhibits vascular SMC
      proliferation.

PMID- 9278558
TI  - Compartmentation of folate metabolism in rat pancreas: nitrous oxide inactivation
      of methionine synthase leads to accumulation of 5-methyltetrahydrofolate in
      cytosol.
AB  - Folate-dependent one-carbon metabolism and methylation reactions have been
      implicated in the secretory function of the pancreas. Because vitamin B-12
      deficiency perturbs folate metabolism, we determined the effects of nitrous oxide
      inactivation of methionine synthase on the compartmentation of folate metabolism
      in rat pancreas. Rats were exposed to an atmosphere of nitrous oxide and oxygen
      (80 and 20%, respectively) for 18 h; control rats breathed air. Folate coenzyme
      concentrations were determined by HPLC and Lactobacillus casei microbiological
      assay of the cytosolic and mitochondrial fractions of pancreas, which contained
      62 and 46%, respectively, of the total folate. In pancreas of control rats,
      cytosolic folates were 5-methyltetrahydrofolate (31% of total folates),
      tetrahydrofolate (54%) and 5- and 10-formyltetrahydrofolate (6 and 8%,
      respectively). In the rats exposed to nitrous oxide, cytosolic 5
      methyltetrahydrofolate concentrations were significantly greater (59% of total
      folates) and tetrahydrofolate concentrations were significantly lower (32%) than
      in controls; however, total cytosolic folate levels were unaffected by nitrous
      oxide exposure. In controls, mitochondrial folates were composed of 5
      methyltetrahydrofolate (9% of total folates), tetrahydrofolate (60%) and 5- and
      10-formyltetrahydrofolate (22 and 10%, respectively). Exposure to nitrous oxide
      led to significantly lower total mitochondrial folates (1.49 +/- 0.18 vs. 0.75 +/
      0.29 nmol/g, control vs. nitrous oxide, P < 0.05). This was due to a
      significantly lower concentration of tetrahydrofolate and 5
      formyltetrahydrofolate, but not of 5-methyl- or 10-formyltetrahydrofolate. The
      activity of methionine synthase was 85% lower (P < 0.001) in pancreatic extracts
      of rats exposed to nitrous oxide than in controls. These results show that
      cytosolic folates accumulate in pancreas as the 5-methyl derivative at the
      expense of other reduced folates, as happens in liver. However, in contrast to
      results in liver, the mitochondrial folate concentration was lower in the
      pancreas of rats exposed to nitrous oxide, and this decline was limited to the 5
      formyl- and tetrahydrofolate derivatives.

PMID- 9278559
TI  - Lipoic acid reduces the activities of biotin-dependent carboxylases in rat liver.
AB  - In the past, lipoic acid has been administered to patients and test animals as
      therapy for diabetic neuropathy and various intoxications. Lipoic acid and the
      vitamin biotin have structural similarities. We sought to determine whether the
      chronic administration of lipoic acid affects the activities of biotin-dependent
      carboxylases. For 28 d, rats received daily intraperitoneal injections of one of
      the following: 1) a small dose of lipoic acid [4.3 micromol/( kg.d)]; 2) a large
      dose of lipoic acid [15.6 micromol/(kg.d)]; or 3) a large dose of lipoic acid
      plus biotin [15.6 and 2.0 micromol/(kg.d), respectively]. Another group received
      n-hexanoic acid [14.5 micromol/(kg.d)], which has structural similarities to
      lipoic acid and biotin and thus served as a control for the specificity of lipoic
      acid. A fifth group received phosphatidylcholine in saline injections and served
      as the vehicle control. The rat livers were assayed for the activities of acetyl
      CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, and beta
      methylcrotonyl-CoA carboxylase. Urine was analyzed for lipoic acid; serum was
      analyzed for indicators of liver damage and metabolic aberrations. The mean
      activities of pyruvate carboxylase and beta-methylcrotonyl-CoA carboxylase were
      28-36% lower in the lipoic acid-treated rats compared with vehicle controls (P <
      0.05). Rats treated with lipoic acid plus biotin had normal carboxylase
      activities. Carboxylase activities in livers of n-hexanoic acid-treated rats were
      normal despite some evidence of liver injury. Propionyl-CoA carboxylase and
      acetyl-CoA carboxylase were not significantly affected by administration of
      lipoic acid. This study provides evidence consistent with the hypothesis that
      chronic administration of lipoic acid lowers the activities of pyruvate
      carboxylase and beta-methylcrotonyl-CoA carboxylase in vivo by competing with
      biotin.

PMID- 9278560
TI  - Calcium intake and the incidence of forearm and hip fractures among men.
AB  - High calcium intakes are thought to be associated with strong bones and lower
      risk of fractures. However, findings from epidemiologic studies have not been
      consistent. In addition, the vast majority of such studies were conducted among
      women, leading to a relative lack of data concerning men. The objective of this
      study therefore was to investigate the relation between adult calcium intake and
      risk of fractures among men in the Health Professionals Follow-up Study (HPFS).
      During 331,234 person-years of follow-up over an 8-y period, 201 forearm and 56
      hip fractures due to low or moderate trauma were reported among 43,063 men 40-75
      y of age in 1986 when they first completed a questionnaire about diet and
      lifestyle factors. After controlling for age, smoking status, body mass index
      (BMI), physical activity, alcohol consumption and total energy intake, the
      relative risk (RR) of forearm fractures for men in the highest quintile of
      calcium intake (from foods plus supplements) compared with those in the lowest
      quintile was 0.98 [95% confidence interval (CI) = 0.59-1.61; P for trend = 0.78];
      for hip fractures, the comparable RR was 1.19 (95% CI = 0.42-3.35; P for trend =
      0.58). Relative risks for consuming >2.5 glasses (600 mL) of milk per day
      compared with one (240 mL) or fewer per week were 1.06 (95% CI = 0.69-1.62; P for
      trend = 0.82) for forearm fractures and 0.97 (95% CI = 0.39-2.42; P for trend =
      0.56) for hip fractures. In conclusion, these results do not support a relation
      between calcium intake and the incidence of forearm or hip fractures in men.

PMID- 9278561
TI  - The effect of an increase of protein intake on whole-body protein turnover in
      elderly women is tracer dependent.
AB  - To compare the response of whole-body protein turnover with variations in dietary
      protein level, whole-body protein turnover was measured by different stable
      isotope methods in six elderly women (69 +/- 5 y) consuming two levels of protein
      (10 and 20% of total energy, diets A and B, respectively). Protein turnover was
      measured during 12 h of overnight fasting with 15N-glycine with urea and ammonia
      as end products. During the last 4 h of the interval, protein turnover was also
      estimated by -[1-13C]-leucine infusion. Nitrogen balance [diet A, -0.040 +/-
      0.015 g/(kg.d); diet B, 0.002 +/- 0.053 g/(kg.d); mean +/- ] did not differ
      significantly between the diet periods, although all subjects were in negative
      nitrogen balance at the end of diet A. Protein breakdown, as measured with 15N
      glycine, did not differ from results obtained using -[1-13C]-leucine, whereas
      protein synthesis was found to be significantly lower using the former isotope.
      The 15N-glycine method indicated that protein turnover (both synthesis and
      breakdown) was higher in fasting elderly women when they consumed a 20% rather
      than a 10% protein diet, whereas the -[1-13C]-leucine method did not show
      significant differences between the diet periods in the last 4 h of the overnight
      fasting period. However, the relative increase in net protein breakdown when
      comparing diet B with diet A, was comparable for both tracers. These data
      indicate that care is needed with the choice of the tracer used in measuring the
      components of protein turnover in elderly women with the aim of understanding the
      physiological basis behind the adequacy of the level of protein intake.

PMID- 9278562
TI  - Phytoestrogens reduce bone loss and bone resorption in oophorectomized rats.
AB  - To examine a potential role for phytoestrogens in postmenopausal bone loss, the
      oophorectomized (OOX) rat model has been used in three studies to investigate the
      effects of the phytoestrogens coumestrol, zearalanol and a mixture of isoflavones
      on estrogen-dependent bone loss. In the studies of coumestrol and zearalanol, the
      rats were allocated to a control group, a phytoestrogen-treated group (1.5
      micromol coumestrol or 3.1 mmol zearalanol twice per week, intramuscular) or, in
      the coumestrol study, an estrogen-treated group (28.1 nmol, intramuscular). In
      the isoflavone study, the rats were allocated to a control group, an estrogen
      treated group or a treatment group that received 131.25 mg of phytoestrogens per
      week incorporated into the nonpurified rat diet. Bone mineral density was
      measured globally and at the spine and femur at base line and 6 wk post
      oophorectomy. In the coumestrol study, blood and urine samples were collected.
      Compared with the control group, rats receiving coumestrol and zearalanol had
      significantly reduced bone loss at all sites measured. The estrogen-treated group
      had significantly greater bone density than the control and the coumestrol
      treated groups in the spine and global measurements. Coumestrol reduced urine
      calcium excretion and the bone resorption markers pyridinoline and
      deoxypyridinoline after 1 wk of treatment. Oral isoflavone phytoestrogens had no
      effect on oophorectomized rats including bone loss at the dose used. Thus, for
      the first time, the bioactivity of coumestrol and zearalanol in preventing bone
      loss has been demonstrated in a well-recognized model of postmenopausal bone
      loss.

PMID- 9278563
TI  - Polyenylphosphatidylcholine attenuates alcohol-induced fatty liver and
      hyperlipemia in rats.
AB  - Chronic administration of a soybean-derived polyenylphosphatidylcholine (PPC)
      extract prevents the development of cirrhosis in alcohol-fed baboons. To assess
      whether this phospholipid also affects earlier changes induced by alcohol
      consumption (such as fatty liver and hyperlipemia), 28 male rat littermates were
      pair-fed liquid diets containing 36% of energy either as ethanol or as additional
      carbohydrate for 21 d, and killed 90 min after intragastric administration of the
      corresponding diets. Half of the rats were given PPC (3 g/l), whereas the other
      half received the same amount of linoleate (as safflower oil) and choline (as
      bitartrate salt). PPC did not affect diet or alcohol consumption [15.4 +/- 0.5
      G/(kg.d)], but the ethanol-induced hepatomegaly and the hepatic accumulation of
      lipids (principally triglycerides and cholesterol esters) and proteins were about
      half those in rats not given PPC. The ethanol-induced postprandial hyperlipemia
      was lower with PPC than without, despite an enhanced fat absorption and no
      difference in the level of plasma free fatty acids. The attenuation of fatty
      liver and hyperlipemia was associated with correction of the ethanol-induced
      inhibition of mitochondrial oxidation of palmitoyl-1-carnitine and the depression
      of cytochrome oxidase activity, as well as the increases in activity of serum
      glutamate dehydrogenase and aminotransferases. Thus, PPC attenuates early
      manifestations of alcohol toxicity, at least in part, by improving mitochondrial
      injury. These beneficial effects of PPC at the initial stages of alcoholic liver
      injury may prevent or delay the progression to more advanced forms of alcoholic
      liver disease.

PMID- 9278564
TI  - Treatment of rats with dexamethasone or thyroxine reverses zinc deficiency
      induced intestinal damage.
AB  - Structural and functional damage to the intestine and the potential beneficial
      effects of dexamethasone (Dex) and thyroxine (T4) were examined in zinc-deficient
      rats. Rats were assigned to zinc deficient (ZD), control (C) or pair-fed (PF )
      groups and fed for 40 d a zinc deficient (1 mg/kg) diet (ZD rats) or a similar
      diet supplemented with 50 mg Zn/kg (C and PF rats). Some rats of the ZD group
      were treated for the last 10 d with low (250 mg/kg) or high (5 mg/kg) doses of
      Dex or with T4 (100 mg/kg). Serum corticosterone of T4-treated ZD rats did not
      differ from untreated ZD rats. Serum T4 of T4-treated ZD rats did not differ from
      C rats. ZD rats developed ulcerations, inflammation and edema in the small
      intestine, particularly in the jejunum. PF rats did not show mucosal changes
      relative to C rats. ZD rats showed significantly lower crypt cell production rate
      (CCPR) and labeling index (LI) in the three intestinal regions, and lower cell
      migration rate and higher turnover time in the duodenum relative to C rats.
      Sucrase and maltase activities of ZD rats were significantly lower than C rats in
      the three mucosal regions. Treatment with the low dose of Dex resulted in fewer
      ulcerations compared with ZD rats. In rats administered the high dose of Dex or
      T4, all morphological alterations disappeared; the CCPR, LI, cell migration rate,
      cell turnover time and disaccharidase activities did not differ from C rats. In
      conclusion, Dex and T4 exert beneficial effects on zinc deficiency-induced
      intestinal alterations in rats.

PMID- 9278565
TI  - Rates of mitochondrial and peroxisomal beta-oxidation of palmitate change during
      postnatal development and food deprivation in liver, kidney and heart of pigs.
AB  - We measured total, mitochondrial and peroxisomal capacities for beta-oxidation of
      [1-14C]palmitate in homogenates of liver, kidney and heart from pigs within 0.5 h
      after birth (0 h, unfed) and at 24 h (suckled or unfed), 10 d (suckled or 24-h
      food-deprived), 21 d (suckled or 24-h food-deprived) and 5 mo (overnight food
      deprived) of age. Assays were conducted in the absence (total beta-oxidation) or
      presence (peroxisomal beta-oxidation) of antimycin A and rotenone. Mitochondrial
      beta-oxidation was calculated as total minus peroxisomal beta-oxidation. Acid
      soluble products (ASP) from incubation of tissue homogenates from 24-h-old unfed
      pigs with [1-14C]palmitate were analyzed by radio-HPLC. Total and mitochondrial
      beta-oxidation capacities were greater (P < 0.05) at 24 h after birth in liver,
      and at 10 d in kidney and heart, than at 0 or 24 h. Peroxisomal beta-oxidation
      capacity was increased (P < 0. 05) at 24 h after birth in liver and at 10 and 21
      d in heart; in kidney, the capacity was higher during the preweaning period than
      in adults. Across ages, peroxisomal beta-oxidation capacity represented 37 to
      51%, 28 to 41%, and 26 to 31% of total beta-oxidation capacity in liver, kidney,
      and heart, respectively. Food deprivation increased hepatic total beta-oxidation
      at 10 d and decreased peroxisomal beta-oxidation at 24 h but had no effect in
      kidney and heart. Regardless of the presence of respiratory inhibitors, 32%, 31
      to 40%, and 45 to 50% of palmitate carboxyl carbon in acid-soluble products was
      accumulated in acetate in liver, kidney, and heart, respectively. We suggest that
      a high percentage contribution of peroxisomal beta-oxidation may act as a
      compensatory mechanism for piglets to oxidize milk fatty acids during postnatal
      development. Furthermore, acetogenesis may be an important fate of acetyl-CoA
      from beta-oxidation of fatty acids in various piglet tissues.

PMID- 9278566
TI  - Fecal numbers of bifidobacteria are higher in pigs fed Bifidobacterium longum
      with a high amylose cornstarch than with a low amylose cornstarch.
AB  - Twelve young male pigs consumed a purified diet containing wheat bran as fiber
      source. Starch provided 50% of total daily energy either as a low amylose
      cornstarch or as a high amylose (amylomaize) starch. The pigs were given a
      supplement of a freeze-dried probiotic organism (Bifidobacterium longum CSCC
      1941). A block crossover design was used so that at any one time two groups of
      three pigs consumed either the high or low amylose cornstarch without probiotic
      and a further two groups of three pigs consumed either high or low amylose
      cornstarch with probiotic. Neither food intake nor body weight gain was affected
      by diet. Fecal output was higher when pigs were fed the high amylose cornstarch,
      but moisture content was unaffected. Fecal concentrations and excretion of total
      volatile fatty acids were higher when pigs were fed the high amylose cornstarch.
      Concentrations of acetate were unaffected by dietary starch, but those of
      propionate and butyrate were higher when the high amylose cornstarch was
      consumed. Fecal excretion of all three acids was higher during high amylose
      cornstarch feeding. Bifidobacteria were detected in the feces only when pigs were
      fed Bifidobacterium longum. Fecal bifidobacteria counts (expressed per gram of
      wet feces) and their daily fecal excretion were higher when pigs were fed high
      amylose cornstarch. Feeding the probiotic did not alter fecal starch or volatile
      fatty acids. None of the variables studied was affected by the order of feeding
      of starch or probiotic. The data show that a high amylose starch acts as a
      prebiotic in promoting the fecal excretion of probiotic organisms.

PMID- 9278567
TI  - Consumption of retrograded (RS3) but not uncooked (RS2) resistant starch shifts
      nitrogen excretion from urine to feces in cannulated piglets.
AB  - To study the effect of resistant starch (RS) on the route of nitrogen excretion,
      we fed three groups of six cannulated piglets each a diet containing either
      uncooked resistant starch (RS2 ), retrograded resistant starch (RS3 ) or glucose.
      The use of piglets with a cannula at the end of the ileum allowed measurement of
      the amount of nitrogen that entered the colon. Ileal digesta, urine and feces
      were collected quantitatively and weighed, and dry matter, starch and nitrogen
      content were determined. We hypothesized that RS2 would lower colonic absorption
      of nitrogen when compared with RS3 , because RS2 may be more fermentable than RS3
      , thus trapping more nitrogen in bacteria. The piglets fed RS3 had a
      significantly higher production of ileal digesta and feces than the piglets fed
      glucose or RS2 . In the piglets fed RS2 , 44% of the amount of RS fed was
      recovered in the ileal digesta; in the piglets fed RS3 , 71% was recovered. Thus,
      more fermentable material entered the colon in the RS3 -fed piglets than in the
      RS2 -fed piglets. Virtually no starch was recovered in the feces of any dietary
      group. Replacement of glucose by either RS2 or RS3 did not affect nitrogen
      retention but increased fecal nitrogen excretion. Compared with glucose, RS3 but
      not RS2 reduced urinary nitrogen excretion, mainly in the form of urea, and
      reduced the amount of nitrogen absorbed by the colon when expressed as a
      percentage of the amount of nitrogen entering the colon. This study provides
      evidence that RS3 , but not RS2 , shifts nitrogen excretion from urine to feces
      in cannulated piglets.

PMID- 9278569
TI  - Dietary arginine requirement of juvenile yellow perch.
AB  - We conducted an 8-wk feeding experiment to determine the dietary arginine
      requirement of juvenile yellow perch (Perca flavescens). The basal diet contained
      33 g crude protein/100 g diet (23 g crude protein supplied by crystalline L-amino
      acids and 10 g crude protein supplied by casein and gelatin). Eight dietary
      treatments contained graded levels of L-arginine-HCl ranging from 0.44 to 1.84
      g/100 g dry diet in gradations of 0.2 g/100 g diet. Diets were made
      isonitrogenous with L-glutamic acid and were fed to triplicate groups of fish
      with an initial weight of 11 g/fish. Dietary arginine significantly affected
      weight gain and feed efficiency but not survival. The best weight gain and feed
      efficiency values were 155. 3% increase from initial weight and 0.63,
      respectively. Quadratic regression analyses of weight gain and feed efficiency
      data indicated the dietary arginine requirement to be 1.61 and 1.41 g/100 g diet,
      respectively. We recommend 1.41 g L-arginine-HCl/100 g diet for juvenile yellow
      perch fed purified diets. The recently developed dietary arginine requirements of
      fish are surprisingly similar and generally higher than those of the ureotelic
      mammals and lower than the uricotelic birds.

PMID- 9278568
TI  - Ingestion by men of a combined dose of beta-carotene and lycopene does not affect
      the absorption of beta-carotene but improves that of lycopene.
AB  - A double-blind study was conducted in 10 healthy men to investigate serum beta
      carotene and lycopene responses after ingestion of individual and combined doses
      of beta-carotene (BC) and lycopene. On each dosing day, a baseline blood sample
      was drawn, followed by an oral dose of 0.11 mmol (60 mg) of either all-trans BC
      or all-trans lycopene or by a combined oral dose of 0.11 mmol each. Subjects were
      tested with each of the three doses. The dose type was randomized. Blood (10 mL)
      was drawn at 1, 3, 5, 7, 9, 12 and 24 h after dosing. At 2 and 4 wk after the
      first dose, the protocol was repeated with the other doses. After ingestion of
      the BC dose, serum BC concentrations significantly decreased from baseline at 1
      and 3 h followed by a continuous increase from baseline that was significant at
      12 and 24 h (P < 0.01). Serum lycopene concentrations significantly increased
      from baseline at 5 h after the lycopene dose (P < 0.008) and returned to baseline
      thereafter. Ingestion of a combined dose of BC and lycopene resulted in a
      significant increase in serum concentrations of both BC and lycopene at 24 h (P <
      0.05). The 24-h area under the curve (AUC) for BC was not different when BC was
      ingested alone or with lycopene, whereas the 24-h AUC for lycopene was
      significantly greater when lycopene was ingested with BC than when ingested alone
      (P < 0.05). Our data suggest that ingestion of a combined dose of BC and lycopene
      has little effect on the absorption of BC but improves that of lycopene in men.

PMID- 9278571
TI  - Interpreting epidemiologic studies of diet-disease relationships.
AB  - The purpose of this paper is to examine key issues in the interpretation of
      nutritional epidemiologic study results when the focus is on major chronic
      degenerative diseases of multifactorial etiology. The estimation of disease risk
      associated with a particular dietary factor is influenced by the presence of
      other risk factors within the study population, complicating the interpretation
      of relative risk and odds ratio estimates in this context. Identifying the
      precise role(s) that dietary factors play in the onset or progression of chronic
      diseases is further complicated by the intercorrelation of dietary components and
      by the correlation of dietary patterns with other behavioral and environmental
      factors which may also impart or exacerbate risk of disease. Issues of study
      design and measurement make it difficult to identify relationships in nutritional
      epidemiology, but also thwart the rejection of hypotheses regarding diet-disease
      relationships when studies fail to yield significant associations. In drawing
      causal inferences from epidemiologic findings, it is important to examine
      evidence from a variety of sources and to look for congruence between
      epidemiologic, clinical and laboratory research findings.

PMID- 9278570
TI  - Human amino acid requirements.

PMID- 9278572
TI  - Obesity: common symptom of diverse gene-based metabolic dysregulations.
      Proceedings of a symposium. Little Rock, Arkansas, March 4, 1997.

PMID- 9278573
TI  - Pathophysiology of obesity.

PMID- 9278574
TI  - Body weight set-points: determination and adjustment.
AB  - It is proposed that body weight, like body water and body temperature, is
      physiologically regulated. In the case of body weight, coordinated adjustments in
      both the intake and expenditure of energy serve to stabilize the weights of
      individuals at a specified level and to resist their displacement from this
      level. Obese individuals also display these behavioral and metabolic adjustments
      to weight perturbations and thus appear to actively resist efforts to reduce
      their weight from the elevated levels they ordinarily display. Experimental
      studies of genetically transmitted and diet-induced forms of obesity in animals
      similarly suggest a view of obesity as a condition of body energy regulation at
      an elevated set-point. An individual's set-point for regulated body weight is
      apparently adjustable, shifting over a lifespan in conjunction with naturally
      occurring but still unspecified physiologic changes. Experimentally, the set
      point for body weight can be adjusted by manipulation of specific hypothalamic
      sites. Lesions of the lateral hypothalamus, for example, cause a chronic
      reduction in the level at which laboratory animals regulate body weight. It thus
      appears that hypothalamic mechanisms play a primary role in setting the level at
      which individuals regulate body weight, and it is likely that the genetic,
      dietary and other lifespan influences on body weight are expressed through these
      mechanisms.

PMID- 9278575
TI  - Periods of risk in childhood for the development of adult obesity--what do we
      need to learn?
AB  - The prenatal period, the period of adiposity rebound and adolescence appear to
      represent critical periods for the development of obesity that persists into
      adulthood. Nonetheless, relatively little is known about the extent to which
      incident obesity at each of these intervals contributes to the prevalence of
      adult obesity. Similarly, little is known about the mechanisms that operate at
      each of these critical periods to entrain adult obesity.

PMID- 9278576
TI  - Genetics of human obesity: recent results from linkage studies.
AB  - Excess body fat or body mass relative to height aggregates in families. It is
      commonly recognized that this familial aggregation of human obesity is accounted
      for in part by a significant genetic component. Thus the genetic heritability of
      the obesity phenotypes accounts for approximately 25-40% of the age- and gender
      adjusted phenotypic variances. There is also growing evidence that single-gene
      effects can be detected under appropriate conditions. The focus of research has
      now shifted to candidate genes and DNA markers of various obesity phenotypes. To
      date, linkage results have been published from the Pima Indian Study, the San
      Antonio Family Heart or Diabetes Studies, the Paris Cohort of Obese Siblings, the
      University of Pennsylvania Family Obesity Study and the Quebec Family Study. The
      only genomic scan (with approximately 600 markers) reported to date is that from
      the Pima Indian sibling study. In that study, the strongest evidence for linkage
      with body fat was with markers on chromosome 11q, 6p and 3p. Evidence for linkage
      with markers on 7q was obtained in all family studies with the only apparent
      exception being the Pima Indians. Our own results from the Quebec Family Study
      suggest that there are linkages between body fat, as assessed from
      hydrodensitometry, and markers on 1p32-p22. Other linkages have been reported in
      the past but they are generally based on smaller sample size and weaker evidence.

PMID- 9278577
TI  - The genetics of human noninsulin-dependent (type 2) diabetes mellitus.
AB  - Familial aggregation and concordance in monozygotic and dizygotic twins argue
      strongly for a genetic etiology to noninsulin-dependent diabetes (NIDDM).
      Nonetheless, studies of pathways implicated by the known physiology have failed
      to identify gene defects that can explain the genetic susceptibility. In
      contrast, studies of early onset dominant diabetes have revealed three major loci
      resulting in diminished insulin secretion. Recently, studies have taken a new
      approach to map the genes causing typical NIDDM using large numbers of families
      or sibling pairs. The first reports of these studies have suggested possible loci
      on chromosomes 1, 2 and 12, but no report has been confirmed. Other studies have
      examined the quantitative defects that may be precursors of clinical NIDDM such
      as hyperinsulinemia, hyperglycemia, insulin response to glucose and obesity.
      These studies have suggested additional loci that may contribute to NIDDM
      susceptibility, but the genes responsible for most of these loci remain unknown.
      Studies of NIDDM susceptibility and the role of obesity genes in that
      susceptibility have entered an exciting new phase, but the challenges of complex
      disease genetics in humans will have to be conquered to translate this research
      into preventive or therapeutic benefits.

PMID- 9278578
TI  - Obesity as a pleiotropic effect of gene action.
AB  - Obesity, an easily detected and quantifiable phenotypic endpoint, is often
      considered, colloquially, as a disease. However, the study of obesity in rodents
      suggests that it is merely a convenient indicator of diverse underlying metabolic
      and physiologic dysregulations, rather than a disease entity in itself. To
      illustrate this concept, the differences between the murine Lepob/Lepob and Avy/-
      "obesity" syndromes are delineated. In both syndromes, pleiotropic effects of
      single mutations play a major role in altering the homeostatic regulation of
      energy metabolism and a myriad of extra- and intracellular processes in a
      diversity of tissues and cell types. The Lepob/Lepob syndrome mimics juvenile
      onset obesity, whereas the Avy/- syndrome resembles maturity-onset obesity. The
      Avy/- syndrome has its basis in overabundance of agouti protein, whereas the
      Lepob/Lepob syndrome results from a lack of active leptin hormone. Lepob/Lepob
      mice have a smaller lean body mass, whereas Avy/- mice have a larger lean body
      mass than their respective lean siblings. Lepob/Lepob mice have fewer lung and
      mammary tumors than their lean Lep/- littermates, and Avy/- develop more mammary
      and lung tumors than their lean A/- or a/a siblings. Lepob/Lepob mice are
      infertile or sterile, whereas Avy/- mice are fertile. Thus, although adult
      Lepob/Lepob and Avy/- mice are both obese, many of the other morphologic and
      physiologic attributes of one mutant are diametrically opposite to those of the
      other.

PMID- 9278579
TI  - The role of the agouti gene in the yellow obese syndrome.
AB  - The yellow obese syndrome in mice encompasses many pleiotropic effects including
      yellow fur, maturity-onset obesity, hyperinsulinemia, insulin resistance,
      hyperglycemia, increased skeletal length and lean body mass, and increased
      susceptibility to neoplasia. The molecular basis of this syndrome is beginning to
      be unraveled and may have implications for human obesity and diabetes. Normally,
      the agouti gene is expressed during the hair-growth cycle in the neonatal skin
      where it functions as a paracrine regulator of pigmentation. The secreted agouti
      protein antagonizes the binding of the alpha-melanocyte-stimulating hormone to
      its receptor (melanocortin 1 receptor) on the surface of hair bulb melanocytes,
      causing alterations in intracellular cAMP levels. Widespread, ectopic expression
      of the mouse agouti gene is central to the yellow obese phenotype, as
      demonstrated by the molecular cloning of several dominant agouti mutations and
      the ubiquitous expression of the wild-type agouti gene in transgenic mice. Recent
      experiments have revealed that the hypothalamus and adipose tissue are
      biologically active target sites for agouti in the yellow obese mutant lines.

PMID- 9278580
TI  - Single gene obesities in rodents: possible relevance to human obesity.
AB  - Obesity is a complex phenotype which "resolves" the influences of genes,
      development and environment. In any individual - and in the same individual at
      different times of life - the relative influence of these factors may vary. In
      this sense, obesity is a prototype of many of the diseases now confronting
      medical science. Among the most important concepts regarding such phenotypes is
      the idea that relevant genes mediate susceptibility to disease in a specific
      environmental context, not the inevitable occurrence of the phenotype regardless
      of the environment. Individuals with otherwise potent genetic predisposition to
      obesity will be lean in an environment of food deprivation/high demand for
      physical activity, and individuals not genetically predisposed to obesity may
      become so in an environment that includes tasty, calorically dense foods and/or
      few inducements to physical activity. Thus, in any effort to elucidate the
      genetic bases for susceptibility to obesity, the "environment" in which the
      obesity is occurring remains a critical factor regarding what sorts of genes will
      be identified. Because the genes that mediate susceptibility to obesity may
      affect energy intake, energy expenditure and/or the partitioning of calories
      between lean tissues and fat, the ability to define the gross metabolic basis for
      the obesity is very important in determining which genes are relevant to the
      phenotype. Because it is so difficult to experimentally define/control the
      environment of humans, and because the attainment of an obese state may actually
      rectify the metabolic differences predisposing to obesity, animal models of
      obesity have been looked at intensively for clues to the relevant genes in
      humans. Over the past 40 years, a series of autosomal dominant (Yellow) and
      recessive (obese, diabetes, tubby, fat, fatty) obesity mutations have been
      described in mice and rats. The molecular cloning of all of these genes has been
      accomplished within the past 4 years, providing an exciting array of new reagents
      for the molecular analysis of obesity. These genes encode molecules that appear
      to interact in physiologic systems that influence body fat stores. The genes and
      their apparent functions are summarized in the Table . The locations of these
      genes in the genomes of rodents and human are known, as are their genetic
      structure/sequence. Thus, their role(s) in human obesity can now be assessed
      directly.

PMID- 9278581
TI  - Mapping of mouse obesity genes: A generic approach to a complex trait.
AB  - Identification of genes underlying any complex trait such as obesity is an
      important and difficult problem in genetics. Traditional candidate gene
      approaches cannot be relied on to identify all of the genes influencing a complex
      trait, and positional cloning is very laborious. With the advent of new tools and
      methods, however, comprehensive approaches to the identification of any genes
      underlying complex traits are now available. Quantitative trait locus (QTL)
      mapping is a general technique to map Mendelian factors influencing complex
      traits. The QTL approach involves the crossing of two strains that differ in the
      trait of interest to produce F2 or back-cross progeny, individually phenotyping
      and genotyping each progeny, and statistically associating the typed markers and
      the phenotype. QTL mapping has been used in the last 4 years to map genes for a
      wide variety of traits, including body weight and growth, obesity,
      atherosclerosis and susceptibility to cancer in the mouse, and hypertension,
      hyperactivity and arthritis in the rat. QTL mapping has also been used to map
      genes in pigs, poultry, cows, fish and plants. Once a trait has been located in a
      chromosomal subregion, identifying the underlying gene remains a significant
      problem. A monogenic model must be developed, isolating one gene influencing a
      trait from other genes affecting the same phenotype. Then the positional
      candidate strategy, which relies on a combination of mapping to a chromosomal
      subregion followed by a survey of the interval to see if attractive candidates
      reside there, becomes practical.

PMID- 9278582
TI  - Potential role of TNFalpha and lipoprotein lipase as candidate genes for obesity.
AB  - To maintain body weight, metabolic efficiency was promoted during evolution; two
      candidate genes for body weight regulation are lipoprotein lipase (LPL) and tumor
      necrosis factor-alpha (TNFalpha). Human fat cells do not synthesize lipid, but
      rely on LPL-mediated plasma triglyceride hydrolysis. Adipose LPL is elevated in
      obesity. Following weight loss, LPL is elevated further, suggesting attempts to
      maintain lipid stores during fasting and to replenish lipid stores during
      refeeding. Muscle LPL is regulated inversely to adipose LPL. Thus, an increased
      adipose/muscle LPL ratio would partition dietary lipid into adipose tissue and
      would explain some of the variability in weight gain when humans are exposed to
      excess calories. Adipose tissue TNFalpha expression is increased in obese rodents
      and humans and may be important in obesity. When insulin-resistant rodents were
      injected with anti-TNF binding protein, insulin action improved, suggesting a
      link between insulin resistance and TNF. TNF is expressed at higher levels in
      muscle cells of insulin-resistant subjects, and TNF may inhibit LPL expression.
      Overall, TNF may function to make the subject less obese by inhibiting LPL and
      rendering the animal more insulin resistant. Obesity has many components, both
      metabolic and behavioral. However, the metabolic changes resulting from LPL and
      TNF likely played a role in regulating body adipose tissue during much of human
      evolution and continue to affect human obesity today.

PMID- 9278604
TI  - Emerging and reemerging infections. Progress and challenges in the subspecialty
      of infectious disease pathology.
AB  - Emerging and reemerging infections are attracting greater attention from the
      public health and medical communities. Pathologists and other physicians are
      increasingly aware of the importance of the subspecialty of infectious disease
      pathology as a tool for diagnosis, surveillance, and research of emerging
      infections. In this communication, we describe the role that infectious disease
      pathologists have played during the last 2 years in broadening our understanding
      of selected emerging infections, including such examples as new variant
      Creutzfeldt-Jakob disease and bovine spongiform encephalopathy, leptospirosis,
      microsporidiosis, Ebola hemorrhagic fever, and cyclosporiasis. The significance
      of providing pathology services, especially the autopsy, to patients with
      potentially hazardous communicable diseases is discussed with the supposition
      that it is unethical to exclude or withhold health care from a patient based on
      his or her underlying disease or on risk factors for acquiring a disease. The
      increasing occurrence of infectious diseases imported into the United States and
      other nations, including human immunodeficiency virus-1 group O, dengue fever,
      tuberculosis, malaria, diphtheria and cholera in immigrants and travelers, and
      Ebola virus in nonhuman primates, emphasizes the necessity for pathologists of
      having competence with infectious disease pathology. It is critical that new
      generations of pathologists not only be trained in the subspecialty of infectious
      disease pathology, but that they also be willing participants in the diagnosis
      and investigation of infectious diseases. The lack of training programs for
      infectious disease pathologists, as well as the deficiency in infectious disease
      pathology support for ongoing and future epidemiologic investigations and
      research, has led to the broadening of pathology services and initiation of a
      dedicated section of Infectious Disease Pathology at one of the nation's premier
      public health institutions, the Centers for Disease Control and Prevention in
      Atlanta, Ga. Together with preexisting groups of medical and veterinary
      infectious disease pathologists at universities, the Armed Forces Institute of
      Pathology, the US Army Medical Research Institute of Infectious Diseases, and the
      National Institutes of Health, this new program will significantly strengthen the
      capability of the United States to respond to future challenges of emerging and
      reemerging infections, both in this country and abroad.

PMID- 9278605
TI  - Human monocytic and granulocytic ehrlichioses. Discovery and diagnosis of
      emerging tick-borne infections and the critical role of the pathologist.
AB  - Human monocytic ehrlichiosis and human granulocytic ehrlichiosis are emerging
      tick-borne infections in the United States. The clinical presentations of these
      two distinct, potentially life-threatening infections are fever, headache,
      myalgia, and other diagnostically nonspecific symptoms. Physician awareness is
      lacking and appropriate diagnostic tests are still not widely available. Because
      few documented cases have been autopsied, the pathology of human monocytic
      ehrlichiosis and human granulocytic ehrlichiosis is incompletely described. In
      human monocytic ehrlichiosis, bone marrow and hepatic granulomas and multiorgan
      perivascular lymphohistiocytic infiltrates have been observed. In human
      granulocytic ehrlichiosis, opportunistic fungal and viral infections have been
      important findings. To expedite an analysis of the pathology and pathogenesis of
      the human ehrlichioses, it is proposed that a Registry of Pathology of Human
      Ehrlichioses be established.

PMID- 9278606
TI  - Laboratory diagnosis of Cyclospora infections.
AB  - The laboratory diagnosis of newly recognized infectious agents, such as
      Cyclospora cayetanensis, is frequently problematic because appropriate diagnostic
      techniques and algorithms are not available. The methods currently available for
      diagnosis of Cyclospora are described and compared, including concentration
      procedures, examination of wet preparations, various staining techniques, and the
      use of molecular-based assays. Because of the autofluorescent properties of the
      oocysts, particular attention is drawn to the role of fluorescent microscopy in
      providing a rapid, inexpensive, and sensitive technique for diagnosis of
      Cyclospora infections in stool samples. In addition to text descriptions,
      photomicrographs are provided to illustrate Cyclospora oocysts in wet and stained
      preparations and compare them with Cryptosporidium and Isospora oocysts, the
      other two most common coccidian infections in man.

PMID- 9278607
TI  - Pathology of Penicillium marneffei. An emerging acquired immunodeficiency
      syndrome-related pathogen.
AB  - OBJECTIVE: To summarize current knowledge regarding the opportunistic dimorphic
      fungal pathogen Penicillium marneffei. Clinical presentation, differential
      diagnosis, mycology, histopathology, diagnostic serology, in vitro antifungal
      agent susceptibility testing, and therapy are discussed for human
      immunodeficiency virus-infected individuals primarily living in Southeast Asia.
      DATA SOURCES: Critical evaluation of peer-reviewed publications located through
      an electronic literature database search, supplemented by unpublished
      observations, were used to prepare this report. STUDY SELECTION: Studies were
      selected based on either the fungal name Penicillium marneffei, penicilliosis,
      penicilliosis marneffei, or a combination of these. DATA EXTRACTION: Articles
      were reviewed with appropriate data being abstracted and then synthesized into
      the review. DATA SYNTHESIS: Differential diagnostic criteria for tissue diagnosis
      and laboratory identification of the fungus are detailed. The usefulness of
      mycoserology and antifungal therapy are evaluated. CONCLUSIONS: Penicillium
      marneffei is an emerging pathogen, primarily among patients with acquired
      immunodeficiency syndrome residing in Southeast Asia. Although infection caused
      by P marneffei is endemic to this portion of the world, cases are being diagnosed
      and treated involving individuals who have traveled to this region. Penicilliosis
      marneffei can clinically resemble tuberculosis, molluscum contagiosum,
      cryptococcosis, and histoplasmosis. The successful treatment of P marneffei
      infection is dependent on its rapid and accurate diagnosis.

PMID- 9278608
TI  - Pathology of experimental Ebola virus infection in African green monkeys.
      Involvement of fibroblastic reticular cells.
AB  - BACKGROUND: Ebola virus has been responsible for explosive lethal outbreaks of
      hemorrhagic fever in both humans and nonhuman primates. Previous studies showed a
      predilection of Ebola virus for cells of the mononuclear phagocyte system and
      endothelial cells. OBJECTIVE: To examine the distribution of lesions and Ebola
      virus antigen in the tissues of six adult male African green monkeys
      (Cercopithecus aethiops) that died 6 to 7 days after intraperitoneal inoculation
      of Ebola-Zaire (Mayinga) virus. METHODS: Tissues were examined histologically,
      immunohistochemically, and ultrastructurally. RESULTS: A major novel finding of
      this study was that fibroblastic reticular cells were immunohistochemically and
      ultrastructurally identified as targets of Ebola virus infection. CONCLUSIONS:
      The role of Ebola virus-infected fibroblastic reticular cells in the pathogenesis
      of Ebola hemorrhagic fever warrants further investigation. This is especially
      important because of recent observations indicating that fibroblastic reticular
      cells, along with the reticular fibers they produce, maximize the efficiency of
      the immune response.

PMID- 9278609
TI  - Human papillomavirus type in anal epithelial lesions is influenced by human
      immunodeficiency virus.
AB  - BACKGROUND AND OBJECTIVE: Infection with human immunodeficiency virus (HIV)
      increases the risk for human papillomavirus (HPV)-associated genital neoplasia.
      Human immunodeficiency virus-infected patients also have higher rates of
      treatment failure and more rapid neoplastic progression. Impaired immune function
      does not entirely explain these clinical observations. This pilot project was
      designed to investigate the hypothesis that HIV infection is associated with
      changes in HPV type and integration within anogenital lesions that could explain
      the increased risk of neoplastic progression. METHODS: Anal neoplastic lesions
      from patients with and without HIV infection were analyzed for the presence,
      type, and integration status of HPV by colorimetric in situ hybridization. Tissue
      localization of HIV was evaluated by p24 immunohistochemistry and HIV-1 DNA
      polymerase chain reaction. Results for matched histology were compared for the
      two patient groups. RESULTS: For all lesions, the presence of high-risk HPV types
      and multiple HPV types was strongly associated with HIV infection (P = .003 and
      .0003, respectively). For lesions with matched histology there was no association
      of HPV integration with HIV status. Tissue localization of HIV did not
      significantly influence HPV type or integration. CONCLUSIONS: The presence of
      high-risk HPV types and multiple types within low-grade lesions may explain the
      increased risk of neoplastic progression in HIV patients. Colocalization of HIV
      and HPV does not appear to be required for this effect. There is no evidence that
      HPV integration is influenced by HIV infection.

PMID- 9278610
TI  - Viral isolation from cases of epidemic neuropathy in Cuba.
AB  - OBJECTIVE: To investigate the possibility of a viral agent in the central nervous
      system of patients with epidemic neuropathy. DESIGN: Virus isolation attempts, in
      cell cultures and suckling mice, from cerebrospinal fluid (CSF) of neuropathy
      patients and controls undergoing lumbar puncture for unrelated reasons. Serologic
      studies in patients, contacts, and controls. SETTING: An epidemic of optic and
      peripheral neuropathy affected more than 50,000 people in Cuba in 1991 through
      1993. Illness was associated with dietary limitations and increased physical
      demands accompanying the shortages of food and fuel experienced in Cuba since
      1989. Most patients responded to parenteral vitamin therapy, and the epidemic
      began to subside when oral vitamin supplementation was begun for the entire Cuban
      population. RESULTS: Coxsackievirus A9 (five isolates) and a similar, less
      cytopathic virus (100 isolates) were recovered from 105 (84%) of 125 CSF
      specimens from neuropathy patients. The strains with light cytopathic effect were
      antigenically related to Coxsackieviruses A9 and B4 by cross-neutralization and
      immunoblotting assays. Virus persisted in CSF of some patients for 1 to 12
      months. Cerebrospinal fluid from patients and both types of virus from cell
      culture produced illness, including complete posterior flaccid paralysis, in
      newborn mice, and virus was reisolated from the mice. Mouse tissues and sural
      nerve biopsy specimens from patients were stained by immunoperoxidase and
      colloidal gold techniques using hyperimmune rabbit antisera against the virus
      with light cytopathic effect. CONCLUSIONS: Coxsackievirus A9 or an antigenically
      related agent with a light cytopathic effect was present in CSF of 84% of 125
      patients with epidemic neuropathy. The role of these agents, probably in
      combination with nutritional factors, in the pathophysiology of the disease
      requires further investigation.

PMID- 9278611
TI  - Latent Epstein-Barr virus infection demonstrated in low-grade leiomyosarcomas of
      adults with acquired immunodeficiency syndrome, but not in adjacent Kaposi's
      lesion or smooth muscle tumors in immunocompetent patients.
AB  - BACKGROUND: Incidence of smooth muscle tumors is increased in patients with human
      immunodeficiency virus infection and organ transplant recipients. Smooth muscle
      tumors in immunocompromised patients often occur in unusual locations and exhibit
      evidence of latent infection by clonal, presumably tumorigenic, Epstein-Barr
      virus (EBV). OBJECTIVE: To investigate the presence of EBV latent infection in
      smooth muscle tumors in patients with acquired immunodeficiency syndrome and in
      immunocompetent patients. DESIGN: Twenty-two extrauterine, extraintestinal smooth
      muscle and myofibroblastic tumors were reviewed pathologically, and clinical
      charts were screened. Tumors were malignant (15 patients), benign (6 patients),
      and borderline (1 patient). Tissue specimens were investigated for latent EBV
      infection by latent membrane protein immunocytochemistry and EBV-encoded RNA in
      situ hybridization. SETTING: University Hospital of the University of Nancy,
      France. PATIENTS: Patients were 18 adults and four children. Two adults had
      acquired immunodeficiency syndrome. Both had low-grade leiomyosarcomas located in
      adrenal gland. Moreover, in patient 1, leiomyosarcoma was multifocal in
      pericardium and lymph node; in lymph node, muscle tumor was adjacent to nodal and
      skin Kaposi's lesions. RESULTS: In both patients with acquired immunodeficiency
      syndrome and leiomyosarcoma, latent infection by EBV could be demonstrated in
      tumor cells, contrasting with absence of detectable EBV infection in adjacent non
      neoplastic tissues and nearby Kaposi's lesions. Latent infection by EBV could not
      be demonstrated in smooth muscle and myofibroblastic tumors in immunocompetent
      patients. CONCLUSIONS: Latent EBV infection is associated with smooth muscle cell
      tumors in immunocompromised patients, but not in immunocompetent patients.

PMID- 9278613
TI  - Viral RNA in duodenal bile of cirrhotic patients with chronic hepatitis C.
AB  - BACKGROUND: Hepatitis C virus (HCV) has been detected in blood, saliva, urine,
      semen, breast milk, and tears. To our knowledge, bile has not yet been
      investigated. We observed histologic immunoreactivity in bile with an antibody to
      c100 protein in four of five HCV-positive cirrhotic livers, but also in two HCV
      negative controls owing to a focally present cross-reacting antigen. METHODS: We
      collected duodenal bile from 13 cirrhotic patients during endoscopic evaluation
      of varices (10 HCV, three controls) and assayed for HCV by reverse transcriptase
      polymerase chain reaction. RESULTS: Viral RNA was detected in the bile of 8 of 10
      seropositive patients and in 0 of 3 seronegative controls. CONCLUSION: Hepatitis
      C virus RNA and an antigen immunoreactive with anti-c100 protein are present in
      bile in a proportion of cirrhotic patients with chronic HCV. It remains to be
      determined whether the virus is intact or degenerate, and whether it is shed into
      bile from hepatocytes or is a contaminant from blood or other secretions.

PMID- 9278612
TI  - Immunohistochemical and in situ localization of Crimean-Congo hemorrhagic fever
      (CCHF) virus in human tissues and implications for CCHF pathogenesis.
AB  - BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is a potentially fatal disease
      that occurs in parts of Africa, Asia, and eastern Europe, and that is caused by a
      recently emerged bunyavirus. Rapid laboratory diagnosis of CCHF infection is
      essential and is currently performed by virus isolation and serology.
      Histopathologic studies have been limited to a small number of cases, and little
      is known about the cellular tropism of CCHF virus and the pathogenesis of this
      disease. DESIGN: We conducted a retrospective case analysis of 12 patients with a
      diagnosis of CCHF infection, confirmed by virus isolation, who were evaluated at
      the Special Pathogens Unit, National Institute for Virology, South Africa. The
      clinicopathologic features of CCHF and the diagnostic role of virus isolation as
      compared with serology, immunohistochemistry, and in situ hybridization were
      evaluated. Additionally, the distribution of CCHF virus in human tissues was
      examined. RESULTS: The clinical and histopathologic features of CCHF resemble
      those of other viral hemorrhagic fevers. Of the 12 patients with virus isolation
      confirmed CCHF infection, 5 were positive by serology, 10 by
      immunohistochemistry, and 5 by in situ hybridization. Immunohistochemistry and in
      situ hybridization analyses showed that the mononuclear phagocytes, endothelial
      cells, and hepatocytes are main targets of infection. Association of parenchymal
      necrosis in liver with viral infection suggests that cell damage may be mediated
      by a direct viral cytopathic effect. CONCLUSIONS: The diagnosis of CCHF,
      suspected by history and clinical features, can be supported histopathologically.
      However, since the pathologic features resemble those of other viral hemorrhagic
      fevers, an unequivocal diagnosis can be made only by laboratory tests. The
      utility of immunohistochemistry as a sensitive and rapid diagnostic modality was
      established by the high degree of concordance with virus isolation. Infection of
      mononuclear phagocytes, endothelial cells, and hepatocytes may play a critical
      role in the pathogenesis of CCHF.

PMID- 9278614
TI  - Epstein-Barr virus--Associated hemophagocytic syndrome. A cause of fever of
      unknown origin in human immunodeficiency virus infection.
AB  - A 26-year-old human immunodeficiency virus-positive man presented with fever of
      unknown origin, pancytopenia, and elevated liver function tests. Numerous
      diagnostic tests and empiric therapeutic interventions remained unsuccessful.
      Splenectomy eventually established the diagnosis of Epstein-Barr virus-associated
      hemophagocytic syndrome. Treatment with foscarnet, acyclovir, prednisone, and
      vinblastine resulted in complete recovery. Three months later, Hodgkin's disease,
      a previously reported complication of the Epstein-Barr virus-associated
      hemophagocytic syndrome, was diagnosed. Fever, pancytopenia, and hepatic
      dysfunction are common complication of advanced human immunodeficiency virus
      infection and can be caused by a variety of opportunistic pathogens. A high index
      of suspicion is critical for the management of this otherwise fatal disorder
      because once the diagnosis is made, even patients with advanced disease benefit
      from aggressive therapeutic intervention, as demonstrated in the case presented.

PMID- 9278615
TI  - Routine rapid Mycobacterium species assignment based on species-specific allelic
      variation in the 65-kilodalton heat shock protein gene (hsp65).
AB  - OBJECTIVE: To assess the utility of automated DNA sequencing strategies for
      Mycobacterium species assignment and surrogate rifampin susceptibility testing of
      Mycobacterium tuberculosis complex isolates in a hospital-based clinical
      microbiology laboratory. DESIGN: Consecutive patient specimens (n = 161) cultured
      in BACTEC 12B medium (growth index of 50 or greater) or on solid media
      (Lowenstein-Jensen) were analyzed. A 360-bp segment of a gene (hsp65) encoding a
      65-kd heat shock protein was sequenced to identify species-specific allelic
      polymorphism. Identification of sequence variation in the rpoB gene encoding the
      beta subunit of RNA polymerase was used as a surrogate method to assess rifampin
      susceptibility in M tuberculosis complex isolates. RESULTS: The automated DNA
      sequencing strategies rapidly identified virtually all mycobacteria (158 [98%] of
      161) to the species level and unambiguously characterized the region of rpoB that
      contains mutations responsible for rifampin resistance in M tuberculosis strains.
      With few exceptions, DNA sequence-based species assignment data agreed with
      diagnostic information obtained by conventional methods. All discrepancies were
      due to ambiguous biochemical test data or interpretation. The rifampin
      susceptibility phenotype was correctly predicted for all strains by rpoB
      sequencing. CONCLUSIONS: Rapid mycobacterial species assignment based on hsp65
      sequencing can be routinely performed in a hospital diagnostic microbiology
      laboratory setting. The method is especially useful for identification of
      fastidious organisms, such as Mycobacterium genavense. Sequencing of the rifampin
      resistance-determining region of rpoB provides a convenient surrogate strategy
      for predicting rifampin susceptibility in M tuberculosis complex isolates.

PMID- 9278616
TI  - Bacterial filamentation of Yersinia pestis by beta-lactam antibiotics in
      experimentally infected mice.
AB  - OBJECTIVE: To identify alternatives to streptomycin for treating pneumonic
      plague, we evaluated beta-lactam antibiotics to treat experimental pneumonic
      plague in mice. METHODS: Mice were exposed to a lethal inhaled dose of Yersinia
      pestis and treated with beta-lactam antibiotics administered every 6 hours,
      starting 42 hours postexposure. RESULTS: The mice died or were euthanized in
      extremis 3 days postexposure. We observed marked bacterial filamentation of Y
      pestis in the tissues of mice treated with ceftazidime (10/10 mice), aztreonam
      (9/10 mice), or ampicillin (1/10 mice), but not in the tissues of mice treated
      with cefotetan, cefazolin, ceftriaxone, or saline. There was no evidence of
      septation of the filamentous bacteria by light or electron microscopy. The
      filamentous bacteria were confirmed as Y pestis based on their reactivity with
      rabbit anti-Y pestis F1 serum. CONCLUSIONS: Marked bacterial filamentation of Y
      pestis can be produced in vivo by certain beta-lactam antibiotics. This
      antibiotic-induced morphologic change is important because filamentous bacteria
      in clinical samples could possibly be confused with filamentous actinomycotic
      organisms.

PMID- 9278617
TI  - Disseminated toxoplasmosis. Unusual presentations in the immunocompromised host.
AB  - OBJECTIVE: Owing to the increasing number of patients with acquired
      immunodeficiency syndrome and immunosuppressed transplant patients, disseminated
      Toxoplasma gondii has emerged as a potentially fatal pathogen. Common
      presentations include encephalitis, pneumonia, and myocarditis. The objective of
      this report is to describe the clinical course, histologic features, and outcome
      in two immunocompromised patients with disseminated toxoplasmosis presenting with
      parasitemia and panniculitis. MATERIALS AND METHODS: Two cases of disseminated
      toxoplasmosis presenting with parasitemia (patient 1) and panniculitis (patient
      2) were retrieved from the clinical, surgical, and autopsy pathology archives of
      Vanderbilt University Medical Center, Nashville, Tenn. The histology and
      diagnostic approaches used are reported. Charts were reviewed for primary
      diagnosis, therapy protocols, clinical presentation of infection, and outcome.
      RESULTS: Patient 1 developed a clinically unexplained sepsis syndrome shortly
      after heart transplantation; T gondii parasitemia was diagnosed by examination of
      peripheral blood smears. The diagnosis was confirmed at autopsy. Patient 2 was a
      child undergoing induction chemotherapy for lymphoma who developed rapidly
      progressive neurologic deterioration accompanied by a maculopapular skin rash; T
      gondii panniculitis was diagnosed retrospectively when histologic examination was
      combined with immunohistochemistry. Autopsies performed in both cases confirmed
      widely disseminated infection. CONCLUSIONS: Disseminated toxoplasmosis should be
      considered in the differential diagnosis of immunocompromised patients with
      culture-negative sepsis syndrome, particularly if combined with neurologic,
      respiratory, or unexplained skin lesions. Examination of Wright's-stained
      peripheral blood smears or antitoxoplasma immunoperoxidase studies of skin
      biopsies may be diagnostic and allow rapid initiation of antibiotic therapy.
      Autopsy findings contributed to both of our cases by documenting the wide-spread
      heavy parasite burden and demonstrating numerous diagnostic T gondii cyst forms.

PMID- 9278618
TI  - Diagnosis of Enterocytozoon bieneusi (microsporidia) infections by polymerase
      chain reaction in stool samples using primers based on the region coding for
      small-subunit ribosomal RNA.
AB  - OBJECTIVE: Enterocytozoon bieneusi is the most prevalent microsporidian causing
      chronic diarrhea in patients with acquired immunodeficiency syndrome. The current
      methods used for routine diagnosis of infections caused by microsporidia are
      based on microscopic detection of the microorganism spores in stained smears. We
      evaluated the usefulness of the polymerase chain reaction (PCR) technique as a
      tool to diagnose Enterocytozoon bieneusi infections, using the species-specific
      diagnostic primer pair EBIEF1/EBIER1 on stool samples that were also analyzed by
      optical microscopy. DESIGN: To perform PCR in such samples, we developed a novel
      protocol to obtain DNA free of PCR inhibitors. This protocol was based on
      disruption of spores using glass beads and overnight digestion with proteinase K;
      final purification was accomplished with the RapidPrep Micro Genomic DNA
      isolation Kit for Cells and Tissues (Pharmacia Biotech Inc, Piscataway, NJ). We
      also evaluated this approach on aliquots of a sample fixed in formalin from 1 to
      10 days. PATIENTS AND SAMPLES: We evaluated the PCR technique on 64 stool samples
      obtained from patients with acquired immunodeficiency syndrome who had persistent
      chronic diarrhea. Patients were from Spain, Brazil, Germany, and the United
      States. RESULTS: Using this approach, we could confirm the presence of E bieneusi
      in all 17 positive samples; no false-positive results were observed. We could
      also amplify E bieneusi DNA in 10 aliquots of one sample fixed up to 10 days in
      10% formalin. CONCLUSION: We conclude that PCR technology is very suitable for
      species identification of microsporidia in stool samples and may have a potential
      application in prospective studies in formalin-fixed samples.

PMID- 9278619
TI  - A patient with acquired immunodeficiency syndrome and untreated Encephalitozoon
      (Septata) intestinalis microsporidiosis leading to small bowel perforation.
      Response to albendazole.
AB  - BACKGROUND: Encephalitozoon (Septata) intestinalis is a common disseminating
      opportunistic intestinal microsporidian affecting patients with acquired
      immunodeficiency syndrome. This microsporidian does respond to albendazole
      therapy. A patient with acquired immunodeficiency syndrome and chronic diarrhea
      presented to George Washington University Hospital in January of 1996. Despite
      appropriate surgical specimens, no etiology had been found to explain his
      cholecystitis, cystitis, and enteritis 3 months previously at another hospital.
      DESIGN: Tissue specimens were analyzed by light microscopy, using hematoxylin
      eosin and the Armed Forces Institute of Pathology Brown-Brenn microsporidia
      stain, and by transmission electron microscopy. Urine and stool specimens were
      analyzed by modified chromotrope 2R trichrome and chitin fluorochrome stains and
      by transmission electron microscopy. RESULTS: At George Washington University
      Hospital, disseminated E intestinalis was diagnosed from duodenal biopsy, urine,
      and stool specimens. On the 14th day of oral albendazole therapy, a partial small
      bowel resection was performed to correct a perforation (air under the diaphragm).
      There was no enterocyte microsporidian infection at that time, only spores
      undergoing macrophage digestion. Review of previous specimens showed severe E
      intestinalis cholecystitis, cystitis, and enteritis. Albendazole was restarted
      and, after 2 weeks, the patient had negative stool and urine specimens.
      CONCLUSIONS: Encephalitozoon intestinalis symptomatically targets many organs,
      including the urinary bladder. To our knowledge, this is the first tissue
      documented case of cystitis. Left untreated with albendazole, small bowel
      infection can lead to perforation and peritonitis.

PMID- 9278620
TI  - A new and improved "quick-hot Gram-chromotrope" technique that differentially
      stains microsporidian spores in clinical samples, including paraffin-embedded
      tissue sections.
AB  - OBJECTIVE: This report describes a new and improved "quick-hot Gram-chromotrope"
      staining technique that detects microsporidian spores in clinical specimens, such
      as stool, urine, saliva, nasopharyngeal fluid, and bronchoalveolar lavage
      samples, as well as in formalin-fixed and paraffin-embedded tissue sections.
      DESIGN: In this procedure, the samples are stained in heated (50 degrees C to 55
      degrees C) solutions of crystal violet and iodine used in Gram's stain, followed
      by a modified chromotrope solution (heated to 50 degrees C to 55 degrees C). The
      modified stain is composed of chromotrope 2R (1%), fast green (0.15%), and
      phosphotungstic acid (0.25%). RESULTS: With this stain and the new protocol,
      microsporidian spores are stained dark violet against a pale green background,
      and the total staining time is shortened to 5 minutes. CONCLUSIONS: This new
      technique is fast, reliable, and simple. It can be easily adapted for use in
      clinical laboratories.

PMID- 9278621
TI  - Immunoperoxidase and immunofluorescent staining of Rickettsia rickettsii in skin
      biopsies. A comparative study.
AB  - OBJECTIVE: To compare immunofluorescent and immunoperoxidase staining of
      Rickettsia rickettsii in skin biopsies of patients suspected of having Rocky
      Mountain spotted fever (RMSF). DESIGN: Immunofluorescent staining results for R
      rickettsii from skin biopsies of patients suspected of having RMSF were obtained
      by computer and chart review. Immunoperoxidase staining for R rickettsii was
      performed on formalin-fixed, paraffin-embedded skin biopsies from the same
      patient population. PATIENTS: Twenty-six patients who were clinically suspected
      of having RMSF were included in this study. Skin biopsies of these patients were
      examined for evidence of RMSF by immunofluorescence and routine histology. MAIN
      OUTCOME MEASURES: The sensitivity and specificity of both immunofluorescent and
      immunoperoxidase staining techniques were calculated. The chi 2 method was used
      to assess significance. RESULTS: Both tests were highly significant for the
      detection of R rickettsii (P < .01). The sensitivity and specificity of the
      immunofluorescent and immunoperoxidase staining techniques for the identification
      of RMSF were identical. No significant difference between these tests was
      identified (P > .05). CONCLUSION: The sensitivity and specificity of
      immunofluorescent and immunoperoxidase staining of R rickettsii in routinely
      processed, paraffin-embedded skin biopsies of patients suspected of having RMSF
      are identical. Although not as rapid as the immunofluorescent technique,
      immunoperoxidase staining of R rickettsii has advantages over the
      immunofluorescent technique; these include easier antigen localization and
      concomitant viewing of the corresponding histopathology.

PMID- 9278622
TI  - Distinguishing lipid pseudomembranes from larval cestodes by morphologic and
      histochemical means.
AB  - BACKGROUND: Contributors regularly submit specimens to our institute and suggest
      a diagnosis of cestode infection, but the structures in question are actually
      lipomembranous changes that produce lipid pseudomembranes. This required a
      reproducible method to distinguish lipid pseudomembranes from body walls of
      cestodes. METHODS: We describe and compare the morphologic and histochemical
      features of specimens from 20 patients. Nine specimens represented lipid
      pseudomembranes, and 11 represented one of the following five entities:
      cysticercus, coenurus, sparganum, hydatid of Echinococcus granulosus, or
      metastatic solid-bodied cyclophyllidean (possibly cysticercoid) larval cestodes.
      Specimens were stained with hematoxylin-eosin, Gomori's methenamine-silver, and
      72-hour oil red O. Nine patients with cestodes, and all with lipid
      pseudomembranes, presented with subcutaneous lesions. RESULTS: In all specimens,
      oil red O provided marked contrast between lipid pseudomembranes and surrounding
      tissue, but focal or minimal contrast between larval cestodes and surrounding
      tissue. Unlike hematoxylin-eosin, Gomori's methenamine-silver stain produced
      distinctly different staining patterns in larval cestodes and lipid
      pseudomembranes. CONCLUSIONS: This technique readily permitted a simple,
      reproducible, and accurate distinction between lipid pseudomembranes and cestode
      body walls and distinguished between body walls of different cestodes.

PMID- 9278623
TI  - Small-cell lung cancer, paraneoplastic cerebellar degeneration and the Lambert
      Eaton myasthenic syndrome.
AB  - Several cancers, especially lung, ovarian and breast, can cause paraneoplastic
      cerebellar degeneration. The presence of different antineuronal antibodies
      associated with different cancers and paraneoplastic cerebellar degeneration
      suggests that several immunological mechanisms may result in the same
      neurological disorder. In patients with small-cell lung cancer, paraneoplastic
      cerebellar degeneration may occur with or without Hu antineuronal antibodies
      (HuAb), indicating that patients with the same tumour can develop paraneoplastic
      cerebellar degeneration by different immunological mechanisms. Furthermore,
      paraneoplastic cerebellar degeneration sometimes occurs in association with the
      Lambert-Eaton myasthenic syndrome. In order to try to understand the clinical
      implication of antineuronal antibodies in patients with small-cell lung cancer,
      we examined the serum of 57 patients with presenting symptoms of paraneoplastic
      cerebellar degeneration for the presence of HuAb and P/Q- and N-type voltage
      gated calcium channel antibodies. Patients with paraneoplastic cerebellar
      degeneration who were HuAb positive were compared with HuAb negative patients
      with respect to neurological symptoms, course of the neurological disorder,
      response to treatment, tumour prognosis, pathological findings, and cause of
      death. The tumour outcome and serological findings of these patients were also
      compared with those of 109 small-cell lung cancer patients without paraneoplastic
      syndromes of the CNS. Titres of HuAb were classified as 'high' (immunoblot titre
      > 1:10,000) or 'low' (< 1:10,000), the latter similar to the antibody titres
      detected in some small-cell lung cancer patients without paraneoplastic symptoms.
      Twenty-five patients with paraneoplastic cerebellar degeneration (44%) had high
      titres of HuAb, four (7%) had low titres of HuAb, and 28 (49%) were HuAb
      negative; for clinical comparisons with the patients with high titres of HuAb,
      the four patients with low antibody titres were included in the HuAb negative
      cohort. None of the 109 small-cell lung cancer patients without paraneoplastic
      symptoms had high titres of HuAb. The presence of high titres of HuAb defined a
      subset of patients who differed from the HuAb negative paraneoplastic cerebellar
      degeneration cohort, HuAb positive patients were more likely to be female (P <
      0.01), to have multifocal neurological disease (brainstem encephalopathy and
      sensory neuropathy being common extracerebellar manifestations) (P < 0.002), and
      be severely disabled (P < 0.005). A total of nine patients (16%) from both
      paraneoplastic cerebellar degeneration groups developed electrophysiologically
      confirmed Lambert-Eaton myasthenic syndrome. Seven of these nine patients had
      serum available for P/Q-type voltage-gated calcium channel antibody testing and
      all seven were positive. In addition, 20% of HuAb negative paraneoplastic
      cerebellar degeneration patients without clinically identified Lambert-Eaton
      myasthenic syndrome had P/Q-type voltage-gated calcium channel antibodies, while
      only 2% of small-cell lung cancer patients without paraneoplastic symptoms had
      these antibodies. Treatment of the tumour and/or immunomodulation did not alter
      the course of paraneoplastic cerebellar degeneration, but improved Lambert-Eaton
      myasthenic syndrome symptoms. At the time of death, in 60% of HuAb positive and
      20% of HuAb negative paraneoplastic cerebellar degeneration patients, the tumour
      was either not evident or localized to the chest (P < 0.007); neurological
      disease was the cause of death of 65% HuAb positive paraneoplastic cerebellar
      degeneration and 10% HuAb negative paraneoplastic cerebellar degeneration
      patients (P < 0.001). (ABSTRACT TRUNCATED)

PMID- 9278624
TI  - Pallidotomy in Parkinson's disease increases supplementary motor area and
      prefrontal activation during performance of volitional movements an H2(15)O PET
      study.
AB  - Supplementary motor area and right dorsal prefrontal cortex activation in
      Parkinson's disease is selectively impaired during volitional limb movements.
      Since posteroventral pallidotomy improves motor performance in Parkinson's
      disease patients 'off' medication (i.e. off medication for 9-12 h), we
      hypothesized that it would also concomitantly increase supplementary motor area
      and dorsal prefrontal cortex activation. Six Parkinson's disease patients with a
      median total motor Unified Parkinson's Disease Rating Scale (UPDRS) of 52.5
      (range 34-66) 'off' medication underwent unilateral right posteroventral
      pallidotomy. The patients had H2(15)O PET when 'off' medication before and 3-4
      months after surgery. Each PET study comprised four to six measurements of
      regional cerebral blood flow either at rest or while performing regularly paced
      joystick movements in freely selected directions (forward, backward, left or
      right) using the left hand. Pre- and postoperative scans were performed in an
      identical manner and the associated levels of activation were compared using
      statistical parametric mapping. After pallidotomy, the median total motor UPDRS
      score 'off' medication decreased by 34.7% (P = 0.03) and mean response times of
      joystick movements following the pacing tones improved by 13.8% (P = 0.08).
      Relative increases in activation of the supplementary motor area and right dorsal
      prefrontal cortex were observed during joystick movements (P < 0.001). Decreased
      activation was seen in the region of the right pallidum (P = 0.001). We conclude
      that pallidotomy reduces pallidal inhibition of thalamocortical circuits and
      reverses, at least partially, the impairment of supplementary motor area and
      dorsal prefrontal cortex activation associated with Parkinson's disease.

PMID- 9278625
TI  - Metabolic correlates of pallidal neuronal activity in Parkinson's disease.
AB  - We have used [18F]fluorodeoxyglucose and PET to identify specific metabolic
      covariance patterns associated with Parkinson's disease and related disorders
      previously. Nonetheless, the physiological correlates of these abnormal patterns
      are unknown. In this study we used PET to measure resting state glucose
      metabolism in 42 awake unmedicated Parkinson's disease patients prior to
      unilateral stereotaxic pallidotomy for relief of symptoms. Spontaneous single
      unit activity of the internal segment of the globus pallidus (GPi) was recorded
      intraoperatively in the same patients under identical conditions. The first 24
      patients (Group A) were scanned on an intermediate resolution tomograph (full
      width at half maximum, 8 mm); the subsequent 18 patients (Group B) were scanned
      on a higher resolution tomograph (full width half maximum, 4.2 mm). We found
      significant positive correlations between GPi firing rates and thalamic glucose
      metabolism in both patient groups (Group A: r = 0.41, P < 0.05; Group B: r =
      0.69, P < 0.005). In Group B, pixel-based analysis disclosed a significant focus
      of physiological-metabolic correlation involving the ventral thalamus and the GPi
      (statistical parametric map: P < 0.05, corrected). Regional covariance analysis
      demonstrated that internal pallidal neuronal activity correlated significantly (r
      = 0.65, P < 0.005) with the expression of a unique network characterized by
      covarying pallidothalamic and brainstem metabolic activity. Our findings suggest
      that the variability in pallidal neuronal firing rates in Parkinson's disease
      patients is associated with individual differences in the metabolic activity of
      efferent projection systems.

PMID- 9278626
TI  - Learning manual pursuit tracking skills in patients with Parkinson's disease.
AB  - Evidence from a number of sources identifies the putamen and its ultimate
      cortical projection sites as forming a possible substrate for motor learning. The
      present paper describes two experiments which explored motor learning of a
      pursuit tracking task under first (position) and second (velocity) order control
      dynamics, in patients with Parkinson's disease on and off (experiment 2 only)
      their normal dopaminergic medication. In neither experiment did the medicated
      patients show evidence of significant impairment in learning the tasks. In the
      velocity tracking task, however, the patients off medication showed significantly
      less improvement in performance with practice. The discussion considers a number
      of possible interpretations of this finding. Contemporary cognitive theories of
      motor learning consider behavioural change with practice to be the combined
      action of an automatic procedural system, together with input from a conscious
      declarative system. Development of declarative knowledge about the task may have
      changed the nature of the process involved, from a visually guided task to a more
      predictive one based upon an internal representation. Evidence from various
      sources suggests that patients with Parkinson's disease have particular problems
      with this mode of control, thus making the task more difficult. It is suggested
      that motor control deficits have not been adequately considered in previous
      studies on motor learning, and that the evidence from clinical studies for a role
      of the putamen/supplementay motor area in motor learning remains equivocal.

PMID- 9278627
TI  - Movement-related potentials in Parkinson's disease. Motor imagery and movement
      preparation.
AB  - Movement-related potentials (MRPs) associated with voluntary movements reflect
      cortical activity associated with processes of movement preparation and movement
      execution. Early-stage pre-movement activity is reduced in amplitude in
      Parkinson's disease. However, it is unclear whether this neurophysiological
      deficit relates to preparatory or execution-related activity, since previous
      studies have not been able to separate different functional components of MRPs.
      Motor imagery is thought to involve mainly processes of movement preparation,
      with reduced involvement of end-stage movement execution-related processes.
      Therefore, MRP components relating to movement preparation and execution may be
      examined separately by comparing MRPs associated with imagined and actual
      movements. In this study, MRPs were recorded from 14 subjects with Parkinson's
      disease and 10 age-matched control subjects while they performed a sequential
      button-pressing task, and while they imagined performance of the same task. Early
      stage pre-movement activity was present in both Parkinson's disease patients and
      control subjects when they imagined movement, but was reduced in amplitude
      compared with that for actual movement. Movement execution-related components,
      arising predominantly from the primary motor cortex, were relatively unaffected
      in Parkinson's disease subjects. However, motor preparatory processes, probably
      involving the supplementary motor area, were reduced in amplitude overall and
      abnormally prolonged, indicating impaired termination following the motor
      response. Further, this impaired termination of preparatory-phase activity was
      observed only in patients with more severe parkinsonian symptoms, and not in
      early-stage Parkinson's disease.

PMID- 9278628
TI  - Responses to cued signals in Parkinson's disease. Distinguishing between
      disorders of cognition and of activation.
AB  - Impairment of movement execution in Parkinson's disease could be due to disorders
      of cognition and/or of activation. These two factors are hard to separate by
      measuring response times only. Therefore, in this study response force and event
      related EEG potentials were measured continuously during tasks in which subjects
      had to respond to cued signals. Fifteen patients with Parkinson's disease and 15
      healthy subjects were studied during two tasks: (i) the 'clock task', in which
      the signal's identity was fully precued but its presentation time was uncertain
      and (ii) the 'validity task' in which the cue did not always predict the response
      validly. Thus, the clock task required more sustained attention, and the validity
      task sometimes required fast switching. The patients generally responded slower
      than control subjects. In the clock task, the response times of both groups
      changed to the same extent with presentation time, whereas in the validity task
      the patients were additionally slower than the control group with invalidly cued
      signals. The patients generally had a weaker response force and a lower rate of
      force production. In the clock task, both force measures changed with
      presentation time in the control group only, whereas in the validity task, the
      two measures increased in both groups to the same extent with invalidly cued
      signals. The contingent negative variation amplitudes in the patients' event
      related EEG potentials were reduced, reflecting reduced activation of movement
      preparation, whereas lateralization of the motor cortices (i.e. the lateralized
      readiness potential) did not differ significantly between groups, reflecting
      unimpaired response selection. Force and contingent negative variation were
      generally reduced in the patients showing that their general slowing is at least
      partially due to impaired activation. Task-specific problems added to the general
      activation deficit; the lack of modulation of response force by presentation time
      revealed pronounced deficits of activation in the monotonous clock task. The
      specific delay of responses with invalidly cued signals, unparalleled by
      activation measures, might suggest a problem of cognition. The task-specific
      deficits may reflect a basic dilemma for patients with Parkinson's disease:
      cognitive problems may arise in complex tasks but disorders of activation may
      become pronounced in more simple, monotonous tasks.

PMID- 9278629
TI  - Retrieval of old memories: the temporofrontal hypothesis.
AB  - Extensive neuropsychological testing is reported on two chronic patients with
      combined temporopolar and prefrontal damage, dominantly left-hemispheric, and, as
      control, one chronic patient with bi-hemispheric prefrontal damage. The principal
      finding is that combined temporofrontal damage, but not substantial prefrontal
      damage alone, results in marked retrograde memory deficits while leaving
      intelligence and new learning relatively unimpaired. Although their general world
      knowledge was good, the temporopolar patients demonstrated retrograde memory
      impairments on several tests of past events and faces of previously famous
      people. With respect to retrograde autobiographical memory, one of the
      temporopolar patients was severely impaired and the other was judged to be
      moderately impaired. The control patient appeared to be normal. These results,
      together with corresponding data from related single case and dynamic imaging
      studies, strongly support a crucial role of the temporofrontal junction area in
      the ecphory of old memories.

PMID- 9278630
TI  - Patients with cerebellar lesions cannot acquire but are able to retain
      conditioned eyeblink reflexes.
AB  - The purpose of these experiments was to examine the role of the human cerebellum
      in the acquisition and retention of conditioned reflexes. Normal human subjects
      and patients with cerebellar lesions were tested for their capacity to acquire,
      retain and express conditioned eyeblink responses. In acquisition tests, subjects
      were trained in a delay classical conditioning paradigm using a tone conditioned
      stimulus and a midline forehead tap as an unconditioned stimulus. While normal
      subjects developed anticipatory eyeblinks to the tone in one session, patients
      with cerebellar lesions failed to acquire conditioned responses in four
      consecutive training sessions. The conditioning deficit was bilateral even in
      patients with a unilateral cerebellar pathology. The same groups of subjects were
      tested for the presence of eyeblinks to a visual threat. In these experiments,
      both normal subjects and patients with cerebellar lesions exhibited a high level
      of responding when they saw an object approaching their face. These eyeblinks to
      the visual threat are probably naturally acquired conditioned responses because
      they extinguish in normal subjects if they are not reinforced by the
      unconditioned cutaneous stimulus. In addition, the stimulus of seeing an
      approaching object blocks the acquisition of classically conditioned eyeblinks to
      a new conditioned stimulus in normal subjects. These data imply that patients
      with cerebellar lesions who cannot acquire new classically conditioned responses
      are able to retain and express conditioned eyeblinks which were acquired before
      the onset of the pathology. Consequently, cerebellum-dependent neural substrates
      which are involved in learning new conditioned reflexes do not seem to be
      required for the storage of naturally learned conditioned responses.

PMID- 9278631
TI  - Early and late losses of motor units after poliomyelitis.
AB  - Motor unit number estimation was employed to assess muscle innervation in 76
      patients with prior poliomyelitis. Of the 68 patients who were < 70 years of age,
      new musculoskeletal symptoms had appeared in all but four; the mean latent
      interval was 38.0 +/- 10.1 years. As expected, there was a high incidence of
      muscles exhibiting denervation in previously affected limbs (87%). However, the
      incidence in supposedly unaffected limbs was also high (65%). Significant
      differences in the degree of denervation were found between muscles of the same
      hands and feet. Judged on the basis of their potential amplitudes, the surviving
      motor units in partially denervated muscles tended to be enlarged. The
      enlargement was proportional to the extent of the denervation and was comparable
      to that found in amyotrophic lateral sclerosis. In some muscles, possibly those
      innervated by failing motor neurons, motor-unit enlargement was not present.
      Needle examination confirmed the high incidences of denervation in affected and
      allegedly unaffected limbs. Of the 188 muscles with EMG features of chronic
      denervation, only nine exhibited fibrillations or positive sharp waves (4.8%).
      Ninety-five muscles of 18 patients were studied a second time after an interval
      of 2 years. Overall, there was a 13.4% reduction in motor-unit number and a 18.4%
      diminution in M-wave amplitude (P < 0.001). The rate of motor-unit loss was twice
      that occurring in healthy subjects aged > 60 years. Analysis of individual
      patients indicated that some were deteriorating more rapidly than others. These
      studies confirm that denervation progresses in patients with prior poliomyelitis
      in both clinically affected and unaffected muscles, and indicate that this
      progression is more rapid than that occurring in normal ageing.

PMID- 9278632
TI  - Idiopathic hypersomnia. A series of 42 patients.
AB  - The features of idiopathic hypersomnia are not well defined. We reviewed clinical
      and laboratory information on 42 subjects with idiopathic hypersomnia and
      obtained detailed follow-up evaluations on 28 of them. Only 29% of subjects had
      'classic' idiopathic hypersomnia with non-imperative sleepiness, long
      unrefreshing naps, prolonged night-time sleep, difficult awakening with sleep
      drunkenness and prominent mood disturbances. Thirty-two percent had clinical
      features similar to narcolepsy, i.e. irresistible sleepiness, short and
      refreshing naps, few problems with awakening and good response to stimulants,
      without cataplexy or any indication of abnormal REM (rapid eye movement) sleep.
      The other 39% had intermediate clinical characteristics. We found no increase in
      the frequency of the human leucocyte antigens associated with narcolepsy.
      Overall, response to stimulants was good in three-quarters of the patients and
      spontaneous improvement of sleepiness occurred in one-quarter. Possible
      aetiologies identified in 10 patients included viral illness, head trauma and
      primary mood disorder. Idiopathic hypersomnia is a rare syndrome in which
      clinical heterogeneity suggests a variable or multifactoral pathogenesis. Only a
      minority of cases correspond to classical descriptions. Stimulants are often
      beneficial and spontaneous improvement appears to be more common than in
      narcolepsy.

PMID- 9278633
TI  - Multiple sclerosis: comparison of the human T-cell response to S100 beta and
      myelin basic protein reveals parallels to rat experimental autoimmune
      panencephalitis.
AB  - The adoptive transfer of autoreactive S100 beta-specific T cells induces
      experimental autoimmune panencephalomyelitis and uveoretinitis in the Lewis rat,
      mimicking the distribution of lesions seen in a subset of patients with multiple
      sclerosis. We studied the frequency and functional properties of the human T-cell
      response to S100 beta in eight patients (two relapsing-remitting multiple
      sclerosis, one chronic-progressive multiple sclerosis, two with multiple
      sclerosis and uveitis, two neuromyelitis optica, one panuveitis) and in seven
      healthy individuals, using bovine S100 beta for T-cell stimulation. Both in
      patients and controls, the frequency of S100 beta-specific T-cell responses was
      half of that obtained for myelin basic protein (MBP), and only 10% of that
      obtained using purified protein derivative (PPD). The stimulation indices
      obtained in response to S100 beta were also less than half those obtained with
      either MBP or PPD. However, four long-term S100 beta-specific T-cell lines were
      established and studied in more detail. The four T-cell lines all exhibited a
      CD4+, CD8-, T-cell receptor alpha beta + surface phenotype and secreted tumour
      necrosis factor-alpha, interferon-gamma, interleukin-10 and interleukin-4 upon
      antigenic stimulation, but they were heterogenous with respect to T-cell receptor
      usage; two T-cell lines expressed V beta 2, one V beta 6.7 and one V beta 13.
      Antigen-specificity was confirmed using bovine S100 beta beta and alpha beta
      isoforms, as well as a recombinant rat S100 beta preparation. The response to
      S100 beta was shown to the HLA-(human leukocyte antigen-) DR-restricted for two
      of the S100 beta-specific T-cell lines. Human S100 beta-specific T-cell lines
      were cytotoxic, although to a lesser extent than MBP-specific T-cell lines
      derived from the same donors. The phenotypic and functional properties of human
      S100 beta-specific T-cell lines raise the possibility that these T cells are
      pathogenic, as they are in the rat. The low frequency and proliferative index of
      S100 beta-specific, as opposed to MBP-specific T-cell responses suggests that the
      T-cell response to this widely expressed calcium-binding protein is under more
      efficient regulatory control.

PMID- 9278634
TI  - Increased immunoreactivity to two overlapping peptides of myelin proteolipid
      protein in multiple sclerosis.
AB  - We tested the proliferative responses of peripheral blood mononuclear cells from
      61 patients with multiple sclerosis, 56 healthy control subjects and 52 patients
      with other neurological diseases to seven synthetic peptides of myelin
      proteolipid protein (PLP) and 19 synthetic peptides of myelin basic protein
      (MBP). Increased proliferative responses to two overlapping PLP peptides, PLP184
      199 and PLP190-209 were found significantly more frequently in blood from
      patients with relapsing-remitting or secondary progressive multiple sclerosis
      (52.3%), but not from those with primary progressive multiple sclerosis (18.2%),
      than in that from healthy control subjects (8.9%) and patients with other
      neurological diseases (20.8%). Reactivity to these PLP peptides was most
      frequently seen in blood from patients with multiple sclerosis of 6-15 years
      duration and with moderate to severe disability (Kurtzke's Expanded Disability
      Status Scale > 4.0); the blood from 15 of 19 patients in this group reacted to
      one or both of the peptides. Both peptides could be recognized by short-term T
      cell lines specific for whole PLP, and lines specific for one or other of the two
      overlapping peptides were able to recognize whole PLP, indicating that these
      peptides can be processed naturally from the intact molecule. This region of PLP
      is encephalitogenic in a number of strains of mice. Samples from multiple
      sclerosis patients did not react more frequently to any of the MBP peptides than
      those from healthy control subjects. The proportions of patients with other
      neurological diseases whose blood responded to the MBP peptides that most
      frequently elicited responses in blood from multiple sclerosis patients were
      significantly lower than the proportions of multiple sclerosis patients and
      healthy control subjects whose blood responded to these peptides.

PMID- 9278635
TI  - The application of multifactorial cluster analysis in the staging of plaques in
      early multiple sclerosis. Identification and characterization of the primary
      demyelinating lesion.
AB  - Tissues from 13 exceptionally early cases of multiple sclerosis were studied to
      identify and characterize the primary demyelinating lesion, using a variety of
      histological and immunocytochemical methods. Multifactorial cluster analysis
      identified five significantly distinct lesion groups, which showed histological
      progression from simple microglial lesions, predominating in tissues from the
      earliest cases, to complex hypercellular fully demyelinated plaques, chiefly
      associated with cases of intermediate duration. Quiescent lesions showing
      evidence of remyelination were found at all stages of the disease studied, but
      hypocellular inactive plaques, were associated with older cases. Evidence is
      presented that initial demyelination is effected by activated resident microglia.
      Undegraded myelin is initially enveloped by membranes bearing fixed complexes of
      immunoglobulin and complement. In contrast with perivenous encephalomyelitis, in
      which demyelination was dominated by T-cell infiltration, multiple sclerosis
      lesions of comparable duration and maturity exhibited humoral immune reactions.
      Parenchymal CD4+ T-cell infiltration developed in association with subsequent
      plaque maturation. These results emphasize the need for lesion staging when
      multiple sclerosis tissues are being used in the investigation of pathogenic
      mechanisms, and suggest that further analysis of the oligoclonal B-cell response
      may be productive in the search for primary provoking antigens.

PMID- 9278636
TI  - Adrenoleukodystrophy: phenotype, genetics, pathogenesis and therapy.
AB  - The occasion of the presentation of the eighth Gordon Holmes Lecture left me
      feeling both honoured and awed, as a result of my review of the Selected Papers
      of Gordon Holmes (Phillips CG: Selected Papers of Gordon Holmes, compiled and
      edited for the Guarantors of Brain. Oxford University Press, 1979), kindly
      presented to me by the sponsors of the meeting. This volume lists 174
      publications produced over a 55-year period, and contains reprints of
      contributions to neuroanatomy, neuropathology, and to disorders that affected the
      adrenal cortex, the spinal cord, the cerebellum and the cerebral cortex. Yet I
      also feel a sense of sadness; the invitation to present the lecture came from the
      late Anita Harding who, such a short time before her illness, gave me personal
      guidance and encouragement. In this lecture I endeavour to follow the example of
      Gordon Holmes, namely the stepwise analysis of a clinical problem, first by
      observation of the patient, followed by the application of techniques that can
      clarify it, leading to new knowledge not only about the specific disorder, but
      also about the nervous system and human biology in general and, it is to be
      hoped, to more effective therapy.

PMID- 9278637
TI  - Pain relief in pancreatic disease.

PMID- 9278638
TI  - Human immunodeficiency virus and lung cancer.

PMID- 9278639
TI  - Systematic review of randomized controlled trials comparing laparoscopic with
      open appendicectomy.
AB  - BACKGROUND: The role of laparoscopic surgery in the management of patients with
      suspected appendicitis is still debated despite a number of recent randomized
      controlled trials (RCTs). METHODS: A systematic review has been undertaken of all
      published RCTs comparing laparoscopic appendicectomy with open appendicectomy.
      Studies were identified through Medline and supplemented with a manual search of
      relevant journals and meeting abstracts. Data were extracted and analysed
      according to predefined criteria. RESULTS: Ten studies were identified, seven of
      which reported results on an intention-to-treat basis. Laparoscopic
      appendicectomy was associated with a longer operating time (8-29 min), a minimal
      reduction in hospital stay and, probably, an earlier return to normal activity.
      It was also associated with a reduced risk of wound infection (odds ratio 2.6)
      with no increase in other complications. However, bias, particularly resulting
      from lack of blinding, makes some of these results difficult to interpret.
      CONCLUSIONS: Laparoscopic appendicectomy was associated with some advantages and
      no obvious disadvantages, apart from prolonged operating time. Future RCTs should
      be blinded to minimize bias, document adequate follow-up and analyse results on
      an intention-to-treat basis.

PMID- 9278640
TI  - Tumour necrosis factor and inflammatory bowel disease.
AB  - BACKGROUND: Tumour necrosis factor (TNF) is a pleiotropic cytokine produced
      largely by macrophages and T lymphocytes. It has been implicated in the
      pathogenesis of numerous immunoinflammatory processes. Recently, a number of
      studies have indicated that anti-TNF antibodies may be of value in the treatment
      of inflammatory bowel disease. METHODS: The literature is reviewed regarding the
      role of TNF in the pathogenesis of inflammatory bowel disease and the results of
      administering TNF inhibitors. RESULTS AND CONCLUSIONS: TNF may have a role in the
      pathogenesis of inflammatory bowel disease. The effects of TNF inhibitors are
      complex and incompletely understood. Anti-TNF antibody strategies may have a role
      in the treatment of acute exacerbations of the disease but are unlikely to be
      appropriate therapies for long-term management.

PMID- 9278641
TI  - Fibrinogen, fibrin turnover, endothelial products and vascular surgery.
AB  - BACKGROUND: Raised plasma fibrinogen levels and markers of fibrin turnover or
      endothelial disturbance are associated with cardiovascular disease. METHODS: This
      is a critical review of the English language literature relating to fibrinogen,
      fibrin degradation products and endothelial products in peripheral arterial
      disease and revascularization surgery. RESULTS AND CONCLUSION: Altered levels of
      plasma fibrinogen and endothelial products are associated with atherosclerosis
      and some studies have shown an association with poor outcome following
      revascularization surgery. Randomized clinical trials of therapies that modify
      thrombotic pathways in patients undergoing surgery for peripheral arterial
      occlusive disease are therefore required.

PMID- 9278642
TI  - Human immunodeficiency virus and lung cancer.
AB  - BACKGROUND: The association of human immunodeficiency virus (HIV) infection with
      lung cancer remains unclear. The presence of multiple risk factors in patients
      with HIV infection makes it difficult to identify a direct cause-effect
      relationship. METHODS: A retrospective study of patients with lung cancer who
      were diagnosed, treated and followed at Harlem Hospital Center, New York, between
      January 1990 and December 1994 was performed. Eleven HIV-seropositive and 116 HIV
      indeterminate patients with histologically proven lung cancer were identified.
      The two groups were compared with regard to age, sex, race, predisposing factors,
      stage of presentation, histological type of the tumours and survival. RESULTS:
      HIV-infected patients with lung cancer were predominantly male smokers who were
      significantly younger than the control HIV-indeterminate patients with lung
      cancer. Although adenocarcinoma was seen more frequently in the HIV-seropositive
      group, the difference was not statistically significant. Survival in HIV-infected
      patients was shorter than that in HIV-indeterminate patients, suggesting that the
      cancer may be more aggressive in HIV-infected patients or that the progression of
      immunoincompetence in these patients may influence survival. CONCLUSION: A direct
      cause-effect relationship between lung cancer and HIV infection is difficult to
      establish in the presence of other risk factors, but the incidence of lung cancer
      may be increasing in HIV-infected men.

PMID- 9278643
TI  - Pharmacological evaluation of portal venous isolation and charcoal haemoperfusion
      for high-dose intra-arterial chemotherapy of the pancreas.
AB  - BACKGROUND: A novel system of complete portal venous isolation and charcoal
      haemoperfusion (PVI-CHP) has been developed in an attempt to increase dose
      intensity while minimizing the systemic toxicity of the cytotoxic agent during
      intra-arterial chemotherapy of the pancreas. METHODS: Mongrel dogs were given
      doxorubicin (3 mg kg-1), infused over a 5-min period via the splenic artery,
      together with PVI-CHP (group 1; n = 5) or without PVI-CHP (group 2; n = 5).
      Plasma doxorubicin concentrations were determined in serial samples obtained from
      the inlet and outlet of the CHP filter and in samples obtained from the left
      jugular vein (systemic levels) for up to 30 min after initiation of drug
      infusion. Subsequently, specimens were obtained from the pancreas, liver and
      heart to determine tissue doxorubicin levels. RESULTS: The mean(s.d.) peak
      systemic concentration of doxorubicin in group 1 was 0.78(0.03) microgram ml-1,
      significantly lower than that in group 2 of 3.49(1.15) micrograms ml-1 (P <
      0.01). The peak concentration of doxorubicin in group 1 was significantly lower
      (more than 90 per cent) than that before filtration (P < 0.01). Tissue
      doxorubicin concentration in the pancreas was similar in both groups. However,
      concentrations in the liver and heart were significantly lower in group 1 than in
      group 2 (P < 0.05). CONCLUSION: These results indicate that PVI-CHP can produce a
      significant reduction in systemic drug exposure and may allow dose
      intensification during intra-arterial chemotherapy for the pancreas.

PMID- 9278644
TI  - Analysis of prognostic risk factors in hepatic resection for metastatic
      colorectal carcinoma with special reference to the surgical margin.
AB  - BACKGROUND: Liver resection for metastatic colorectal cancer has been
      established. Nevertheless, it is still controversial whether the surgical margin
      from the tumour edge to the cut surface of the liver is a significant prognostic
      factor in hepatic resection for colorectal metastatic liver cancer. METHODS: To
      clarify the prognostic risk factors in hepatic resection for colorectal
      metastasis, univariate and multivariate analyses were performed. Between April
      1985 and April 1995, 31 patients underwent curative hepatic resection for
      metastatic colorectal cancer. The clinical and pathological factors were examined
      retrospectively. RESULTS: Overall 1-, 3- and 5-year survival rates of the
      patients were 92, 42 and 39 per cent respectively. Pathological study of 16
      resected specimens with a solitary liver tumour revealed hepatic vein invasion by
      cancer cells in two of 16 cases, portal vein invasion in three, microsatellite
      lesions in two and biliary tract invasion in six cases. In resected specimens
      with a solitary tumour measuring less than 4 cm in diameter, one of these factors
      was observed in only two of nine cases, whereas in specimens with a solitary
      tumour measuring more than 4 cm in diameter, these factors were observed in six
      of seven patients (P < 0.05). The distance from the tumour edge to the
      intrahepatic invasion was less than 10 mm. With univariate analysis, tumour size
      of 4 cm or more in diameter, an interval of 6 months or less between colorectal
      and hepatic resection, four or more gross tumours, bilobar involvement and a
      resection margin from the tumour of less than 10 mm were found to be significant
      factors indicating a poor prognosis. Cox's proportional hazards model identified
      a tumour of 4 cm or more in diameter and a resection margin from the tumour of
      less than 10 mm as poor prognostic factors (P < 0.05). CONCLUSION: In treating
      metastatic colorectal cancer to the liver, the surgical margin should be more
      than 10 mm because occult intrahepatic invasion was always found to be located
      within 10 mm from the edge of the tumour.

PMID- 9278645
TI  - Significance of lymph node involvement at the hepatic hilum in the resection of
      colorectal liver metastases.
AB  - BACKGROUND: The indication for surgical resection of colorectal liver metastases
      should be guided by technical feasibility and expected prognostic benefit. The
      aim of the present study was to analyse the frequency and prognostic significance
      of lymph node involvement of the hepatoduodenal ligament in the resection of
      colorectal liver metastases. METHODS: A series of 126 prospectively documented
      patients who underwent hepatectomy for metastases of colorectal carcinoma was
      analysed. The prognostic factors of patients with complete resection (R0) of the
      metastases were studied by multivariate analysis. RESULTS: R0 resection was
      achieved in 94 per cent. The 30-day mortality rate was 2 per cent. In all
      patients, lymph nodes were excised from the hepatoduodenal ligament, and
      histological evaluation demonstrated tumour infiltration in 28 per cent of the
      patients. Multivariate analysis revealed nodal involvement of the hepatoduodenal
      ligament (P < 0.0001) and synchronous or metachronous appearance of liver
      metastases (P < 0.005) as independent prognostic factors. The 3- and 5-year
      survival rates were 3 and 0 per cent for lymph node-positive patients compared
      with 48 and 22 per cent respectively for the node-negative group. CONCLUSION:
      Infiltration of lymph nodes in the hepatoduodenal ligament is the most important
      prognostic factor following R0 resection of colorectal liver metastases.

PMID- 9278646
TI  - Expression of oestrogen receptor and oestrogen-inducible genes in pancreatic
      cancer.
AB  - BACKGROUND: Previous studies have not been able to demonstrate convincingly
      whether the human pancreas expresses oestrogen receptor and whether there is any
      benefit from antioestrogen therapy in advanced pancreatic cancer. METHODS:
      Oestrogen receptor expression was assessed in normal human pancreas and
      pancreatic cancer tissue by enzyme immunoassay, Northern blot analysis, in situ
      hybridization and immunohistochemistry. The expression of the oestrogen-inducible
      proteins, progesterone receptor, pS2 and ERD5 was also examined. RESULTS: A mean
      of 1.0 (range 0-2.4) fmol oestrogen receptor per mg protein was detected in
      normal pancreas and 0.5 (range 0-1.2) fmol mg-1 in pancreatic cancer. Messenger
      RNA for oestrogen receptor was detected in both normal and cancerous pancreas. In
      situ hybridization and immunohistochemistry, however, failed to localize
      oestrogen receptor expression. Mean (range) expression of progesterone receptor
      in normal and neoplastic pancreas was 1.9 (0.5-3.5) and 2.5 (0.3-9.3) fmol mg-1
      respectively. pS2 and ERD5 were also expressed in normal tissue and pancreatic
      cancer, and expression was localized to ductular epithelium. CONCLUSION: The
      amount of oestrogen receptor detected in pancreatic tissue was small, and may
      account for previous difficulties in its detection. The extent to which it is
      functional in both the normal and malignant pancreas warrants further
      investigation.

PMID- 9278647
TI  - Lymph node metastasis in carcinoma of the body and tail of the pancreas.
AB  - BACKGROUND: There have been no precise reports concerning lymph node metastatic
      involvement in carcinoma of the body and tail of the pancreas. METHODS:
      Histopathological examination of lymph node involvement in 30 specimens obtained
      from patients who underwent pancreatic resection and wide dissection of lymph
      nodes, including para-aortic lymph nodes, for carcinoma of the body and tail of
      the pancreas was performed. RESULTS: Fourteen of 30 patients had lymph node
      involvement. The highest incidence of lymph node involvement was around the
      splenic artery (five of 30 patients), aorta (four of 30) and coeliac trunk (four
      of 30). No significant difference in survival rate between the lymph node
      negative group and the lymph node-positive group was observed, but all patients
      in the positive group died within 2 years after surgery, and four patients with
      para-aortic lymph node involvement died from recurrence within 10 months after
      surgery. Survival rates were significantly worse in patients with
      histopathological extrapancreatic nerve plexus invasion, retropancreatic tissue
      invasion, tumour diameter more than 4 cm, histological portal system vein wall
      invasion and carcinoma invasion of the surgical margins. CONCLUSION: Although
      aggressive extended surgery including para-aortic node dissection has been
      performed, the postoperative survival rate is still low in patients with
      carcinoma of the body and tail of the pancreas. The high incidence of liver
      metastasis after surgery is a prime cause of the poor outcome, and effective
      therapy for postoperative liver recurrence requires evaluation.

PMID- 9278648
TI  - Magnetic resonance imaging of bone metastases: a diagnostic and screening
      technique.

PMID- 9278649
TI  - Retroperitoneoscopic lumbar sympathectomy.

PMID- 9278650
TI  - Local anaesthetic for lower-limb revascularization in high-risk patients.
AB  - BACKGROUND: A few patients with critical limb ischaemia are believed to be too
      unfit for an attempt at revascularization using conventional anaesthesia.
      METHODS: A retrospective analysis was undertaken of 46 revascularization
      procedures performed in high-risk patients for critical limb ischaemia between
      1989 and 1995, in which local anaesthetic techniques were utilized in preference
      to general or spinal anaesthesia. RESULTS: Cumulative survival rates at 6, 12 and
      24 months were 67, 57 and 51 per cent. Primary patency rates were 77 per cent at
      6 months, 67 per cent at 12 months and 53 per cent at 24 months, with associated
      limb salvage rates of 87, 87 and 79 per cent. CONCLUSION: Selective use of local
      anaesthetic techniques extends the benefits of limb salvage to patients
      considered unfit for conventional anaesthesia.

PMID- 9278651
TI  - Efficacy and safety of enoxaparin versus unfractionated heparin for prevention of
      deep vein thrombosis in elective cancer surgery: a double-blind randomized
      multicentre trial with venographic assessment. ENOXACAN Study Group.
AB  - BACKGROUND: Surgery for malignant disease carries a high risk of deep vein
      thrombosis. The aim of this study was to evaluate the prophylactic effect of a
      low molecular weight heparin, enoxaparin, 40 mg once daily, beginning 2 h before
      surgery, compared with that of unfractionated low-dose heparin three times daily.
      METHODS: Patients included were over 40 years of age and undergoing planned
      elective curative abdominal or pelvic surgery for cancer. The study was designed
      as a prospective double-blind randomized multicentre trial with participating
      departments from ten countries. Primary outcome was venous thromboembolism as
      detected by mandatory bilateral venography or pulmonary scintigraphy. Follow-up
      was at 3 months. RESULTS: Some 1115 patients were randomized into the study but
      venograms were inadequate in 460 (41.3 per cent). Of 631 evaluable patients, a
      total of 104 (16.5 per cent) developed thromboembolic complications. The
      frequency was 18.2 per cent in the heparin group and 14.7 per cent in the
      enoxaparin group (95 per cent confidence interval of the difference -9.2-2.3 per
      cent). There were no differences in bleeding events or other complications. One
      patient in the heparin group developed severe thrombocytopenia. There were no
      differences in mortality at either 30 days or 3 months. CONCLUSION: Enoxaparin,
      40 mg once daily, is as safe and effective as unfractionated heparin three times
      daily in preventing venous thromboembolism in patients undergoing major elective
      surgery for abdominal or pelvic malignancy.

PMID- 9278652
TI  - Early effect of carotid endarterectomy on arterial blood pressure measured with
      an ambulatory monitor.
AB  - BACKGROUND: Carotid artery disease and hypertension are associated, and carotid
      endarterectomy is often followed by acute changes in blood pressure. As the
      carotid sinus is responsible for short-term blood pressure control, occlusive
      carotid disease may contribute to the mechanism of preoperative hypertension.
      METHODS: Ten patients undergoing carotid endarterectomy and eight having a
      peripheral bypass procedure were studied 2 weeks before and 2 weeks after
      operation, using home ambulatory blood pressure measurement. RESULTS: A
      significant fall in both mean systolic (-14.4 mmHg) and mean diastolic (-12.7
      mmHg) pressure was observed after carotid endarterectomy (P < 0.006), whereas no
      change was seen in controls. CONCLUSION: These results suggest that there is an
      increase in carotid sinus activity in patients following carotid endarterectomy
      and supports the hypothesis that carotid sinus dysfunction contributes to
      hypertension in patients with carotid artery disease.

PMID- 9278653
TI  - Claudication distance is poorly estimated and inappropriately measured.
AB  - BACKGROUND: Claudication distance is the commonest measure of the disability
      caused by lower-limb occlusive arterial disease. The accuracy of claudication
      distance as a surrogate for handicap has been assessed. METHODS: Seventy patients
      who attended a specialist vascular clinic with intermittent claudication were
      studied prospectively. Patients were asked to estimate their claudication
      distance and maximum walking distance before undergoing both a patient-controlled
      corridor walk and a fixed-speed treadmill walk. RESULTS: The claudication
      distance reported by patients bore little relation to the distance recorded in
      the medical correspondence. There was no correlation between the estimated
      distance and the actual distance walked on either a patient-controlled corridor
      walk or a fixed-speed treadmill walk. Most patients were able to walk
      substantially further at their own speed on the corridor than on the treadmill at
      a slower speed. CONCLUSION: Claudication distance is spuriously estimated,
      inaccurately reported, falsely recorded, inappropriately measured and usually
      misinterpreted. It is of little value in judging the need for treatment.
      Objective measures of the handicap caused by the disability of reduced walking
      distance are required if rational management decisions are to be made.

PMID- 9278655
TI  - Technique for rapid control of bleeding from an aortoenteric fistula.

PMID- 9278654
TI  - Prospective randomized placebo-controlled trial of aprotinin for elective aortic
      reconstruction.
AB  - BACKGROUND: The serine protease antagonist, aprotinin, reduces perioperative
      blood loss in cardiac surgery and orthotopic liver transplantation. A pilot study
      suggested that the drug may also reduce bleeding during infrarenal aortic
      replacement; the aim was to confirm or refute this observation with a
      prospective, randomized, double-blind, placebo-controlled trial. METHODS: Some
      136 patients were randomized to receive either aprotinin, given as a loading dose
      of 2 x 10(6) kallikrein inactivator (KI) units followed by 0.5 x 10(6) KI units/h
      or equal volumes of 0.9 per cent saline. After 80 patients had been randomized
      the infusion dose was doubled to ensure that plasma levels were similar to those
      seen in successful cardiac studies. Blood loss, coagulation and haematological
      parameters were recorded throughout surgery and for 7 days afterwards. Blood was
      transfused to maintain the haemoglobin level at 100 g/l. RESULTS: Four patients
      were withdrawn after randomization when found at laparotomy to be unsuitable for
      the planned reconstruction. The 30-day mortality rate was 4.5 per cent, with no
      excess complications in either group. Blood loss collected on swabs was reduced
      from 480 ml in placebo-treated patients to 379 ml with aprotinin (P = 0.014).
      Blood loss into suction drains in the first 24 h after operation was reduced from
      295 to 205 ml in aprotinin-treated patients (P = 0.002). However, no significant
      reduction was found in intraoperative or total blood loss, or transfusion
      requirement. CONCLUSION: The small reduction in blood loss in patients treated
      with aprotinin demonstrated in this study does not support its use in routine
      elective aortic surgery.

PMID- 9278657
TI  - Magnetic resonance imaging in the evaluation of a high-velocity gunshot wound to
      the thigh.

PMID- 9278656
TI  - Colour duplex scanning and pulse-generated run-off for assessment of popliteal
      and cruropedal arteries before peripheral bypass surgery.
AB  - BACKGROUND: This prospective pilot study compared the diagnostic accuracy of
      duplex scanning and pulse-generated run-off (PGR) with intra-arterial digital
      subtraction angiography (IADSA) for assessment of popliteal, crural and pedal
      arteries, and explored the reliability of investigation with the combination of
      duplex scanning and PGR in patients who needed femorodistal reconstruction.
      METHODS: In 23 limbs, 345 arterial segments were graded independently with duplex
      scanning and IADSA as normal, stenosed or occluded and compared using weighted
      kappa analysis. PGR was rated as good, poor or no run-off and compared with pedal
      arch patency on IADSA. Based on information derived from duplex scanning and PGR
      a vascular surgeon proposed treatment and the distal anastomosis site for bypass,
      which was compared with definitive treatment as determined by IADSA. RESULTS:
      Overall agreement between duplex scanning and IADSA for popliteal and crural
      arteries was moderate (kappa 0.47, 95 per cent confidence interval (c.i.) 0.39
      0.55) with best agreement within the popliteal and proximal tibial arteries.
      Agreement within pedal arteries was fair (kappa 0.35, 95 per cent c.i. 0.17
      0.53). PGR detected good run-off in five of 21 pedal arteries shown to be
      occluded on IADSA. In 16 of 23 patients treatment based on duplex scanning and
      PGR was identical to that based on IADSA. Eight of eleven femoropopliteal
      bypasses were predicted accurately. CONCLUSION: Operative strategy could have
      been based on investigation by duplex scanning and PGR in a substantial number of
      patients scheduled for femoropopliteal bypass surgery. Agreement between duplex
      scanning and IADSA within very distal arterial segments was fair.

PMID- 9278658
TI  - Ultrasonographic imaging of mycetoma.
AB  - INTRODUCTION: The ultrasonographic appearance of mycetoma is described in this
      prospective study. METHODS: One hundred patients with foot swellings had
      sonographic evaluation of the swelling and surgical excision within 2 weeks of
      ultrasonography. The histopathological findings were compared with the
      preoperative images. Some of the excised swellings and grains were also imaged
      and compared with the in vivo findings. RESULTS: The mycetoma grains, their
      capsules and the accompanying inflammatory granulomas have characteristic
      ultrasonographic appearances. In eumycetoma lesions, the grains produce numerous,
      sharp hyper-reflective echoes and there are single or multiple thick-walled
      cavities with no acoustic enhancement. In actinomycetoma, the findings are
      similar but the hyper-reflective echoes are fine, closely aggregated and commonly
      settle at the bottom of the cavities. None of the non-mycetoma foot swellings
      (which included lipoma, ganglion, foreign body granuloma and others) studied had
      these features. CONCLUSION: Ultrasonography is simple, non-invasive, quick,
      reproducible and acceptable to patients. Mycetoma has characteristic
      ultrasonographic features. Furthermore, ultrasonography delineates the extent of
      mycetoma more accurately than clinical examination alone.

PMID- 9278659
TI  - Outcome and predictors of success of biofeedback for constipation.
AB  - BACKGROUND: A study was undertaken to determine outcome and to identify
      predictors of success for biofeedback for constipation. METHODS: Patients who had
      at least one biofeedback session were evaluated whether or not they completed a
      treatment course. Parameters assessed included use of cathartics, number of
      spontaneous bowel movements per week, presence of rectal pain, number of
      biofeedback sessions and results of anorectal physiology. RESULTS: A total of 194
      patients (59 male, 135 female) of median age 71 (range 11-96) years, including 30
      with concomitant rectal pain, were treated. The median number of spontaneous
      bowel movements per week before treatment was 0. Some 35 per cent of patients had
      complete success (three or more spontaneous bowel movements per week with
      discontinuation of cathartics), 13 per cent had partial success (fewer than three
      spontaneous bowel movements per week with continued use of cathartics) and 51 per
      cent had no improvement. Neither patient age, sex nor duration of symptoms
      significantly affected outcome. Only 18 per cent of patients who had between two
      and four sessions had complete success, compared with 44 per cent of those who
      had five or more (P < 0.001). A total of 63 per cent of patients who completed
      the treatment protocol experienced complete success, compared with 25 per cent of
      those who self-discharged (P < 0.0001). CONCLUSIONS: This large study indicates
      that the success rate of biofeedback for patients with constipation is less than
      previously reported. However, the success rate improves significantly after five
      or more sessions and is significantly related to the patient's willingness to
      complete treatment.

PMID- 9278660
TI  - Assessment of ischaemia of the distal part of the gracilis muscle during
      transposition for anal dynamic graciloplasty.
AB  - BACKGROUND: Dynamic graciloplasty is used to create a neosphincter in patients
      with intractable faecal incontinence. When mobilizing the distal gracilis muscle
      from the upper leg, the minor vascular pedicles have to be ligated. This can
      interfere with the vascular supply in this part of the muscle. METHODS: The
      arterial anatomy within the muscle was visualized by means of angiography of 11
      postmortem specimens. To quantify potential acute ischaemia, blood flow in the
      distal gracilis muscle was measured in ten patients with laser Doppler flowmetry
      during mobilization of the muscle. RESULTS: Angiography showed that the main
      vascular pedicle and all minor pedicles drain into one and the same arterial
      system. After clamping of the minor vascular pedicles, blood flow (mean 25.8
      (range 6.5-74.3) perfusion units) did not differ from values obtained before
      clamping (mean 25.4 (range 7.5-68.7) perfusion units). After a mean of 1.8 years,
      all muscles were vital. No correlation existed between the change in muscle blood
      flow and either squeeze pressure (r = -0.2) or functional outcome (r = 0.31).
      CONCLUSION: This study provides direct anatomical and physiological evidence of
      one arterial system within the gracilis muscle. It is therefore questionable
      whether ligation of the minor vascular pedicles is the bottleneck in human
      dynamic graciloplasty. An additional operation for vascular delay may be
      redundant. A prospective randomized clinical study should be performed to compare
      the functional outcome in patients with and without a delay procedure.

PMID- 9278661
TI  - Randomized controlled trial of postoperative radiotherapy and short-term time
      scheduled 5-fluorouracil against surgery alone in the treatment of Dukes B and C
      rectal cancer. Norwegian Adjuvant Rectal Cancer Project Group.
AB  - BACKGROUND: The purpose of the present study was to investigate whether a 1-month
      regimen of postoperative radiotherapy combined with 5-fluorouracil could reduce
      the local recurrence rate and improve survival in patients with Dukes B and C
      rectal cancer. METHODS: One hundred and forty-four patients were randomized to
      surgery alone or surgery combined with postoperative radiotherapy (46 Gy) and
      bolus 5-fluorouracil 30 min before six of the radiotherapy fractions. One hundred
      and thirty-six patients were eligible. RESULTS: The adjuvant treatment was well
      tolerated. After an observation time of 4-8 years, patients in the adjuvant
      treatment group had a cumulative local recurrence rate of 12 per cent compared
      with 30 per cent in the group that had surgery only (P = 0.01). The 5-year
      recurrence-free and overall survival rate was 64 per cent in the adjuvant group
      compared with 46 per cent (P = 0.01) and 50 per cent (P = 0.05) respectively in
      the surgery group. The adjusted relative risk of recurrence and death for the
      adjuvant group was 0.48 (95 per cent confidence interval 0.28-0.82) and 0.56
      (0.33-0.94) respectively. CONCLUSION: The 1-month postoperative combination
      regimen improved treatment results in patients with Dukes B and C rectal cancer,
      in terms of local recurrence rate, recurrence-free survival and overall survival,
      without serious side-effects.

PMID- 9278662
TI  - Late results justify resection for multiple hepatic metastases from colorectal
      cancer.
AB  - BACKGROUND: Whilst hepatic resection is accepted for single colorectal
      metastases, the role of surgery for multiple deposits is less certain. This study
      reports results of a programme of aggressive resection of hepatic metastases.
      METHODS: Of 150 hepatic resections for colorectal metastases, 107 patients have
      completed 1-9 years' follow-up for this actuarial survival analysis. Indications
      for resection were disease confined to the liver, resectability of all metastases
      and preservation of sufficient hepatic parenchyma. RESULTS: One patient (1 per
      cent) died after operation and six (6 per cent) suffered serious complications
      (two surgical and four medical) but with full recovery. Patients who had a
      radical resection (n = 89) had 1- and 5-year survival rates of 94 and 37 per cent
      respectively. A palliative group (n = 18) with disease elsewhere (n = 9) or
      positive histological margins (n = 9) had corresponding survival rates of 56 and
      6 per cent. Univariate analysis of the group who had radical surgery demonstrated
      that survival depended on size of metastases (less than 7 cm) (P = 0.014), width
      of clear resection margin (greater than 5 mm) (P = 0.004) and primary site (P =
      0.010). Factors not affecting outcome were number of metastases, unilateral
      versus bilateral disease, synchronous versus metachronous spread, tumour
      differentiation and Dukes stage. Multivariate analysis demonstrated independent
      survival advantage for small metastases (less than 7 cm) (P = 0.002) and clear
      resection margin greater than 5 mm (P = 0.037). CONCLUSION: Hepatic resection in
      selected patients with single and multiple colorectal hepatic metastases is
      justified.

PMID- 9278663
TI  - Gastric emptying in patients with constipation following childbirth and due to
      idiopathic slow transit.
AB  - BACKGROUND: Idiopathic slow transit constipation (ISTC) is considered to be a
      heterogeneous condition in which patients have varying sites and degrees of
      delayed gastrointestinal transit. The majority of patients have pancolonic
      disease, and colectomy with ileocolorectal anastomosis has been the mainstay of
      surgical treatment. Severe constipation following traumatic childbirth is now
      being recognized and this subgroup of patients may have delayed transit confined
      to the rectosigmoid colon. In theory, proximal transit in these patients should
      be normal. METHODS: Gastric emptying was studied in patients with constipation
      following childbirth or ISTC and in controls. After an overnight fast, both
      patients and controls received breakfast, which consisted of cornflakes, sugar
      and milk. The liquid marker 111In-labelled di-ethylene tri-amine penta-acetic
      acid (DTPA) was added to the milk. A solid marker, 99mTc-labelled colloid, was
      impregnated on to paper and sealed with cellulose. The t1/2 for gastric emptying
      was calculated. RESULTS: Liquid phase emptying was normal in both constipation
      following childbirth and ISTC. Solid phase emptying was delayed significantly in
      ISTC compared with that in patients with constipation following childbirth and
      controls. In addition, half the patients with ISTC had delayed transit through
      the small bowel and proximal colon. Small bowel and colonic transit were normal
      in patients with constipation following childbirth. CONCLUSION: Patients with
      constipation following childbirth represent a distinct subgroup with normal
      proximal gastrointestinal function. Gastric emptying studies may be helpful in
      selecting patients for surgical management of severe constipation.

PMID- 9278664
TI  - Comparison of computed tomography and ultrasonographic imaging in the assessment
      of blunt abdominal trauma in children.
AB  - BACKGROUND: Computed tomography (CT) has become established in the assessment of
      paediatric blunt abdominal trauma. However, advances in diagnostic imaging
      necessitate reassessment of the role of available diagnostic modalities. METHODS:
      Experience at a paediatric teaching hospital over a 5-year period was reviewed,
      with direct comparison of CT against ultrasonographic imaging in 26 children
      presenting with acute blunt abdominal trauma. RESULTS: Intra-abdominal injury was
      diagnosed by CT in 23 of 24 patients compared with 21 on ultrasonography,
      although ultrasonography identified organ-specific injury in only 12 of 24
      patients. CT was superior in the assessment of the multiply injured child, and
      identified spinal and pelvic injuries in three patients. CT augmented plain chest
      radiography in ten patients with associated thoracic injuries. CONCLUSION: CT is
      the imaging modality of choice in children with severe abdominal trauma but
      ultrasonography is a reasonable technique to arouse diagnostic suspicion in less
      severe injuries or where CT is unavailable or delayed.

PMID- 9278665
TI  - Comparison of magnetic resonance imaging and conventional triple assessment in
      locally recurrent breast cancer.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) was compared with triple assessment
      (clinical examination, cytology and mammography) in the differentiation of post
      treatment changes from local recurrence of breast carcinoma. METHODS: Thirty
      patients treated previously by breast conservation surgery and radiotherapy with
      clinical suspicion of local recurrence were evaluated prospectively by triple
      assessment and MRI. Breast MRI was performed on a 1-tesla scanner using a T1
      weighted three-dimensional fast low angle shot pulse sequence before and after
      contrast enhancement. RESULTS: Local recurrence was confirmed histologically in
      14 patients. Of these, mammography identified seven (sensitivity 50 per cent),
      cytology 11 (sensitivity 79 per cent) and breast MRI 13 (sensitivity 93 per
      cent). Compared with histological measurement, breast MRI allowed an accurate
      estimation of the extent of local recurrence (r2 = 0.98). Morphologically
      abnormal areas without contrast enhancement correlated with postradiation
      changes. False-positive contrast enhancement was seen in two patients
      (specificity 88 per cent) in whom histology confirmed inflammatory changes only.
      CONCLUSION: Breast MRI is useful in the evaluation of patients with a high
      clinical suspicion of local recurrence within the irradiated conserved breast.

PMID- 9278667
TI  - Evaluation of the antireflux mechanism following laparoscopic fundoplication.
AB  - BACKGROUND: Laparoscopic Nissen fundoplication is an effective procedure for the
      treatment of gastro-oesophageal reflux disease (GORD), but the underlying
      motility mechanisms that explain the success of this operation remain unclear.
      METHODS: Twenty patients with a history of GORD underwent stationary oesophageal
      manometry and prolonged ambulatory pH monitoring, both before and 3 months after
      fundoplication. RESULTS: Eighteen patients were completely cured of reflux
      symptoms and stopped all antireflux medication after operation. After
      fundoplication there was a significant increase (P < 0.01) in median resting
      lower oesophageal sphincter (LOS) pressure and length. Median residual LOS
      pressure during swallow-induced LOS relaxation also increased significantly after
      operation (P < 0.01). The number of reflux episodes decreased from a median of 48
      to 3 after fundoplication (P < 0.01). The time at pH less than 4 decreased from
      5.7 to 0 per cent in the supine position (P < 0.01), and from 9.8 to 0.2 per cent
      while upright (P < 0.001). CONCLUSION: Early subjective results at 3 months
      following laparoscopic antireflux surgery show improved symptoms. One of the
      mechanisms underlying the antireflux action of fundoplication is an increase in
      median residual LOS pressure at the gastro-oesophageal junction. This may be a
      purely mechanical effect of the fundic wrap extrinsic to the LOS.

PMID- 9278666
TI  - Monocyte activation after open and laparoscopic surgery.
AB  - BACKGROUND: The level of expression of major histocompatibility complex class II
      antigens, human leucocyte antigen (HLA)-DR, on monocytes correlates with the
      development of sepsis after surgery or trauma. Normally interferon (IFN) gamma
      can increase monocyte HLA-DR expression and thus may be a potential biological
      prophylactic antisepsis agent in patients suffering from accidental or surgical
      trauma. The purpose of this study was to determine the capacity of monocytes to
      respond to IFN-gamma after conventional open surgery and laparoscopic surgery of
      similar magnitude. METHODS: A whole blood flow cytometric assay was used to
      measure monocyte HLA-DR antigen expression before and after monocyte activation
      with either IFN-gamma or bacterial lipopolysaccharide (LPS). Blood was obtained
      before operation and on postoperative day 1 from 43 patients undergoing
      conventional open surgery and from 15 undergoing laparoscopic surgery of similar
      magnitude. RESULTS: Whole blood monocyte HLA-DR expression fell significantly
      after both conventional open and laparoscopic surgery. IFN-gamma caused monocyte
      HLA-DR expression to rise by a median (interquartile range) of 43 (26-60) per
      cent and 63 (10-124) per cent before operation in the open and laparoscopic
      groups respectively. However, after operation the corresponding values were 20 (6
      41) per cent and 26 (9-74) per cent (P < 0.003 in all cases). Identical findings
      but of greater magnitude were observed with LPS stimulation before and after
      operation in the two surgical groups. CONCLUSION: Monocyte HLA-DR expression is
      diminished by surgical operations and is relatively refractory to further
      stimulation by IFN-gamma or LPS after surgery. Laparoscopic surgery is as
      suppressive as conventional surgery in this regard. The resistance of
      postoperative monocytes to further activation by IFN-gamma suggests that this
      agent may be ineffective as a biological response modifier after major surgery or
      trauma.

PMID- 9278668
TI  - Spleen-sparing surgical treatment for echinococcosis of the spleen.

PMID- 9278669
TI  - Oesophageal and cardia function in patients with paraoesophageal hiatus hernia.
AB  - BACKGROUND: The decision to add an antireflux procedure when a paraoesophageal
      hernia is repaired is still controversial. The aim of this study was to
      investigate oesophageal and cardia function in these patients to verify whether
      fundoplication was needed. METHODS: Eighteen patients with paraoesophageal hernia
      were evaluated by oesophageal manometry, 24-h pH monitoring, endoscopy and barium
      swallow. All patients underwent surgery including antireflux fundoplication.
      Fourteen patients with sliding hernia plus reflux disease and 16 healthy
      volunteers formed the control groups. RESULTS: Patients with paraoesophageal
      hernia had a shorter lower oesophageal sphincter and a greater acid exposure than
      healthy controls (P < 0.05). Fifteen of 18 patients had either abnormal acid
      exposure and/or a defective lower oesophageal sphincter at manometry.
      Postfundoplication symptoms were observed in only one of 16 patients at 6 months'
      follow-up. CONCLUSION: Since 15 of 18 patients had abnormal acid exposure or were
      considered prone to developing gastro-oesophageal reflux disease because of a
      defective lower oesophageal sphincter, this study strongly supports the need to
      add an antireflux operation to hernia repair.

PMID- 9278671
TI  - Inguinal cord lipoma.

PMID- 9278670
TI  - Randomized controlled trial of an H2-receptor antagonist in gastric cancer.

PMID- 9278672
TI  - Osmotic therapy for acute irreducible stoma prolapse.

PMID- 9278673
TI  - Osmotic therapy for acute irreducible stoma prolapse.

PMID- 9278675
TI  - Prospective comparison of laparoscopy, ultrasonography and computed tomography in
      the staging of gastric cancer.

PMID- 9278676
TI  - Latex allergy: an emerging health hazard for operating theatre staff.

PMID- 9278674
TI  - Retrosternal goitre: a wider view.

PMID- 9278677
TI  - Matrix metalloproteinases.

PMID- 9278678
TI  - Peritoneal seeding of pancreatic head carcinoma following percutaneous
      transhepatic drainage and stenting.

PMID- 9278679
TI  - Laparoscopic and conventional repair of groin disruption in sportsmen.

PMID- 9278680
TI  - Laparoscopic and conventional repair of groin disruption in sportsmen.

PMID- 9278681
TI  - Extending the role of breast-conserving surgery by immediate volume replacement.

PMID- 9278682
TI  - Prospective randomized study of laparoscopic versus open colonic resection for
      adenocarcinoma.

PMID- 9278683
TI  - Prospective randomized study of laparoscopic versus open colonic resection for
      adenocarcinoma.

PMID- 9278684
TI  - Continuous double loop closure: a new technique for repair of laparotomy wounds.

PMID- 9278685
TI  - Thoracoscopic parathyroidectomy of an ectopic mediastinal adenoma.

PMID- 9278686
TI  - Simple technique for endoscopic subfascial dissection of perforating veins.

PMID- 9278687
TI  - Removal of the anus during proctectomy.

PMID- 9278688
TI  - Closure of loop ileostomy.

PMID- 9278689
TI  - Adenocarcinoma arising on the site of a Gelpi retractor after coloanal
      anastomosis for rectal cancer.

PMID- 9278690
TI  - Surgical management of complicated colonic diverticulitis.

PMID- 9278691
TI  - Surgical management of complicated colonic diverticulitis.

PMID- 9278692
TI  - Surgical management of complicated colonic diverticulitis.

PMID- 9278693
TI  - Prospective audit of surgery for varicose veins.

PMID- 9278694
TI  - Allometric algorithms.
AB  - The aim of the present study is to emphasize the applicability and versatility of
      the allometric equation in the biological sciences. This equation (Y = a x Mb)
      was introduced by Huxley (1932) for intra- and interspecific comparisons of
      morphological, physiological and ecological variables (Y), when they are
      expressed as functions of body mass (M). The regression analysis of the
      experimental data, plotted in a double logarithmic scale, yields a straight line,
      which is equivalent to the logarithmic form of the above mentioned allometric
      equation [log Y = log(a) + (b) x log(M)]. Only the exponent (b) can be calculated
      a priori for a given function, based firstly on the corresponding dimensional
      analysis in accordance with the MLT-system of physics, and secondly on one of the
      theories of biological similarity, while parameter (a) is of empirical nature. A
      relevant feature of the allometric equations is that they can be treated
      algebraically to obtain allometric ratios, mass independent numbers (MIN), and
      even dimensionless numbers (M0L0T0), which are valid for all organisms pertaining
      to the same taxonomic classification.

PMID- 9278695
TI  - Ultrasound characteristics of connective tissue around porous hydroxyapatite
      hypodermic implants in rats.
AB  - Adults Sprague-Dawley rats were implanted with porous hydroxyapatite (Interpore
      200), following a procedure different from that of Kawaguchi et al (1992).
      Instead of implanting hydroxyapatite (Ha) in periodontal osseus defects, we
      introduced Ha-implants in the hypodermis of rats. Animals were sacrificed on days
      30, 90 and 150 (six in each stage). The interface between the Ha and connective
      tissue was studied by transmission electron microscopy, with the aim of
      understanding the biocompatibility and mechanisms of union of both parts. The
      connective tissue reaction to the Ha implant was characterized by fibrovascular
      proliferation, with abundant fibroblasts, macrophages, multinucleated giant
      cells, and by the formation of a capsule surrounding the implant. The
      multinucleated giant cells were observed in the interface along all stages and
      exhibited: (a) a progressive increase in mitochondria, ribosomes, rough
      endoplasmic reticulum and vesicles containing particles of Ha; and b) an
      electronlucent material of variable aspect in vesicles contained in their
      cytoplasmic expansions. The prominent cytologic aspects of the multinucleated
      giant cells in the juxta-Ha zone may indicate that both, the biocompatibility and
      the intimate union between connective tissue and Ha, are strongly dependent on
      the presence of these cells.

PMID- 9278696
TI  - Histopathological analysis of sublethal toxicity of zinc chloride to the
      respiratory organs of the airbreathing catfish Heteropneustes fossilis (Bloch).
AB  - Sublethal toxicity of zinc chloride (ZnCl2; 7.5 ppm: 10% of 96 h LC50 value) on
      the aerial (accessory respiratory organs or air sacs) and branchial (gills)
      respiratory organs of Heteropneustes fossilis has been analysed
      histopathologically. Zinc chloride exposure cause certain common but severe
      damage to both tissues. The prominent changes in the accessory respiratory organs
      include periodic deformation of lamellar elements, haemorrhages due to necrosis
      and sloughing off of the respiratory epithelium, and hyperplasia accompanied by
      fusion of secondary lamellae. Subsequently, regeneration of the lamellar system
      from the focal inflammatory tissues takes place. Deposition of glycogen in the
      muscular layer indicates disturbed aerial respiration. The alterations in the
      gills include periodic lifting off of the respiratory epithelium, extensive
      intercellular vacuolization and occasional fusion of secondary lamellae,
      resulting in increased thickness of primary and secondary lamellae. Fusion of
      secondary lamellae reduces the surface area for gaseous exchange. The increased
      thickness of the respiratory epithelium due to uncontrolled hyperplasia of the
      epithelial cells, also increases the diffusion distance between the ambient and
      vascular components. Vasodilation in the secondary lamellae of the gills and
      periodic fluctuations in the mucous cell density are also observed at various
      stages of ZnCl2 exposure.

PMID- 9278697
TI  - Arginase activity of Bufo arenarum embryos is sensitive to external osmotic
      pressure.
AB  - We investigated the impact of environmental osmotic stress on the arginase
      activity if Bufo arenarum embryos. The activity at the first developmental stages
      was not sensitive to extreme variations of osmotic pressure of the environment.
      Later, at gill circulation, opercular fold and right operculum stages, the enzyme
      activity of embryos developed in concentrated solutions decreased significantly
      with respect to control. At complete operculum stage, the arginase activity
      increased 1.3-2.5 fold in all conditions, and was significantly higher in embryos
      grown in distilled water than in control animals.

PMID- 9278698
TI  - In memoriam Professor Jaime Talesnik, MD.
AB  - In memoriam Jaime Talesnik. Born in Santiago, Chile, 18 May 1915; deceased
      Toronto, Canada, 7 April 1996. Medical studies at University of Chile, 1935-1940.
      MD, University of Chile, 1941. Assistant Professor of Physiology, Faculty of
      Biology and Medicine, University of Chile, 1940-45. Rockefeller Research Fellow,
      Banting-Best Institute, Department of Medical Research, University of Toronto,
      Canada, 1945-46. Associate Professor of Physiology, Faculty of Medicine,
      University of Chile, 1947-51. British Council Research Scholar in Pharmacology,
      National Institute for Medical Research, London, England, 1951-52. Associate
      Professor of Pathophysiology, Faculty of Medicine, University of Chile, 1952-63.
      Professor and Chairman, Department of Experimental Medicine, Faculty of Medicine,
      University of Chile, 1963-67. Visiting Professor, Department of Pharmacology,
      University of Toronto, Canada, 1967-69. Professor, Department of Pharmacology,
      University of Toronto, Canada, 1969-81. Professor Emeritus, University of
      Toronto, Canada, 1981. Member Emeritus, Medical Association of Chile, 1991.
      Honorary Member, Chilean Society of Physiological Sciences, 1995. Author of
      textbook of pathophysiology and many articles in scientific journals.

PMID- 9278699
TI  - Selection for high and low number of sternopleural bristles in Drosophila
      ananassae: correlated response in the frequency of chromosome inversions.
AB  - Directional selection for high and low number of sternopleural bristles in
      Drosophila ananassae was applied for 13 generations. The selection produced a
      rapid divergence in the mean number of sternopleural bristles in the replicates
      high and low lines: i-high (H1 -25.75, H2 -25.69); ii-low (L1 -14.16 L2 -13.55);
      iii-control (17.21) lines in G13. Regression coefficients for the high and low
      lines were significantly different from zero. The realized heritability over
      thirteen generations was 21-23 for the high lines and 14-18 for the low lines.
      The results suggest that the number of sternopleural bristles in D. ananassae is
      under polygenic control, with a substantial amount of additive genetic variation.
      Flies of the base population had three chromosome inversions: AL (2L), ZE (2R)
      and DE (3L). The comparisons of chromosome arrangement between high and low lines
      (the G13 generation of selection) indicates significant changes in the inversion
      frequency during the course of selection, providing evidence for correlation
      between the bristle number and particular chromosome arrangements.

PMID- 9278700
TI  - Idiopathic epilepsy with generalized tonic clonic seizures in Antioquia,
      Colombia: is the joint Amerindian and Negroid racial admixture the cause of its
      high prevalence?
AB  - Most Colombian populations stem from the admixture of Caucasians, Amerindians and
      Negroids. In the world, these two latter ethnical groups show a significantly
      higher prevalence of epilepsy than the former one. We tested the hypothesis that
      the high prevalence of idiopathic epilepsy with generalized tonic clonic seizures
      found in the Antioquian population (Paisas), from Colombia, is due to their
      possible joint Negroid and Amerindian ethnic components. We have previously
      demonstrated that inheritance is the principal factor for developing epilepsy in
      this community. Analyses of racial admixture, heterogeneity between populations,
      genetic distance, and phyletic relationships were performed among epileptic and
      non epileptic samples from the Antioquian community. Also Caucasians, Spaniards,
      Basques, Jews, Chileans, Negroids, Amerindians and Mongoloids were included in
      the analysis. Four highly polymorphic blood systems were used as genetic markers:
      RH, MNS, ABO and FY. They were chosen because of their high discriminant power in
      these ethnic groups. In the population affected with idiopathic epilepsy, the
      estimated Negroid and Amerindian rates of admixture were low (3% and 14%,
      respectively). Although, these degrees of admixture can be explained due to
      common ancestral origins, the estimated proportion of Amerindian admixture in the
      epileptic affected population, was significantly higher than the estimated for
      the Non affected Antioquian population. The latter finding is consistent with the
      analysis of heterogeneity between populations that discriminated epileptic
      population from non epileptic Antioquian population (p < 0.05). Epileptic and non
      epileptic Paisas clustered in topology with Caucasians, very close to Spaniards
      and Basques and highly distant from Negroids and Amerindians. Thus, far, the
      origin of the high prevalence of idiopathic epilepsy in the Antioquian (Paisa)
      population cannot be explained by the hypothetical joint Negroid and Amerindian
      ethnical admixture, but using additional genetic markers and other methods of
      racial estimation of admixture it is necessary to corroborate if the Amerindian
      admixture component is significantly higher in the epileptic population than in
      the non epileptic Paisa population.

PMID- 9278701
TI  - Duality in physiological time: Euclidean and fractal.
AB  - The aim of the present study was to differentiate two modalities of intrinsic
      time scales: i- the geometric or Euclidean modality, which is based on the
      constant speed of mass transport or of wave transmission in cylindrical
      structures (arteries, veins, nerves), whose allometric exponent (TE = aMb) is b =
      0.33, where M is body mass (kg) and a the mass coefficient; ii- the fractal time
      scale (TF), which is characteristic of organs with self-similar branching
      structures and with volume-specific flows, whose allometric exponent is b = 0.25.
      The proposed dichotomy could be confirmed by means of the statistical analysis of
      empirical allometric exponents (b). Our findings demonstrate the need to separate
      the chronology of bulk transport at long distances (inter-organic) which follows
      an Euclidean geometry (cylinders), from the fractal time scale, which operates at
      short distances (intra-organic) and is represented by a self-similar branching
      system which determines both the morphometric and physiometric characteristics
      within each organ.

PMID- 9278702
TI  - Visual transduction in vertebrate rods.

PMID- 9278703
TI  - The second messenger for visual excitation in invertebrate phototransduction.
AB  - Invertebrate visual transduction involves a second messenger cascade process that
      leads to an increase in membrane conductance. The identity of the second
      messenger that gates the light-dependent channels is presently a major focus of
      attention. Cyclic GMP, inositol trisphosphate and Ca2+ are the most likely
      candidates for being such a messenger in the species studied so far. Here we
      review the available evidence for each of these molecules.

PMID- 9278704
TI  - Frequency tuning of mechanical responses in the mammalian cochlea.
AB  - The search for mechanisms responsible for the high sensitivity and sharp
      frequency tuning of first-order auditory neurons has produced surprising results.
      The cochlea, the mammalian auditory receptor, responds to acoustic stimuli with a
      sharply frequency tuned, nonlinear vibration that enhances low level stimuli, but
      generates appreciable distortion. This highly sensitive mechanical response is
      achieved by an electro-mechanical feedback process in which outer hair cells
      reinforce cochlear motion at low stimulus intensities.

PMID- 9278705
TI  - Chemical reception in vertebrate olfaction: evidence for multiple transduction
      pathways.
AB  - Odorant detection takes place at the receptor neurons of the olfactory epithelium
      and odorant discrimination relies in an important degree on these chemosensory
      cells. Here we review the evidence for the participation of multiple transduction
      pathways in the mechanisms of odor recognition in olfactory neurons.

PMID- 9278706
TI  - Sodium cyanate: from a promising therapeutic agent to a research tool in high
      altitude physiology.
AB  - Sodium cyanate (NaOCN) first appeared on the biomedical scene as a potential
      therapeutic agent for sickle-cell disease. Although it did not fulfill its early
      promise in the clinic, it proved to be useful as a pharmacological tool in
      physiological research, particularly in the physiology of oxygen transport. NaOCN
      has been especially valuable in the area of investigation which is reviewed here:
      the study of oxygen transport, both in normoxic and in hypoxic conditions, in
      experimental models in which NaOCN was used to induce a shift to the left of the
      oxygen dissociation curve. The classical idea is that a low Hb-O2 affinity is of
      adaptive value for life at high altitudes but it has been challenged by several
      pieces of evidence. One of them is the demonstration of increased survival in
      hypoxic hypoxia of animals with a high Hb-O2 affinity induced by NaOCN. We also
      discuss the advantages and potentially confounding factors which should be taken
      into consideration when interpreting results of studies in which the oxygen
      dissociation curve has been modified by administration of NaOCN.

PMID- 9278707
TI  - Biochemical aspects of cellular antioxidant systems.
AB  - Aerobic life is characterized by a steady generation of reactive oxygen species
      balanced by a similar rate of their consumption by antioxidants. To maintain
      homeostasis, there is a requirement for the continuous regeneration of
      antioxidant capacity, and if this is not met, oxidative stress occurs, resulting
      in pathophysiological events. Cellular protection against oxidative stress is
      organized at multiple levels. Defense strategies include prevention,
      interception, replacement, and repair. These mechanisms are coupled to the
      intermediary metabolism for a continuous supply of energy, reducing equivalents,
      and precursors, and depend on the dietary supply of metabolic fuels and essential
      molecules to allow an optimal cellular functioning.

PMID- 9278708
TI  - Inhibin binding sites in bovine pituitary membranes.
AB  - Membranes derived from bovine pituitary glands free of the neural lobe were used
      to investigate the presence of binding sites for inhibin, a glycoprotein produced
      by the ovarian granulosa cells capable of selectively suppressing FSH secretion
      from the pituitary gland. Optimal concentration of membranes (400 micrograms
      prot) and 125I-bovine inhibin (2 nM) were incubated in a medium containing 50 mM
      Tris-HCl pH 7.4, 0.01 M MgCl2 and BSA 0.01% in a final assay volume of 200
      microliters at 37 degrees C for different time intervals. Non-specific binding
      was estimated using unlabelled inhibin in excess. The time course of specific
      125I-bovine inhibin (2 nM) binding to bovine pituitary membranes is slow with 50%
      binding at approximately 20 min of incubation and reaching equilibrium at 90 min
      of incubation. The kinetic analysis shows an apparent pseudo first order
      association rate constant (Kob) equivalent to 4 x 10(-2) min-1. Following
      equilibrium with the tracer, a large excess of unlabelled inhibin (1.27 microM)
      was able to displace 84% of the specific binding within 120 min of incubation and
      50% of the binding at approximately 40 min. The analysis under displacing
      conditions showed an apparent dissociation rate constant (K2) equals to 1.5 x 10(
      2) min-1 and an apparent association rate constant (K1) equals to 1.3 x 10(9) M
      min-1. Thus, the estimation of the apparent kinetic equilibrium dissociation
      constant (Kd = K2/K2) of the binding of inhibin to bovine pituitary membranes was
      1.2 nM. These results show for the first time the existence of bovine inhibin
      specific binding sites in bovine pituitary, and also that such a binding can take
      place in the absence of either gonadal and/or hypothalamic influences. They also
      contribute to the better understanding of the role of non-steroidal hormones such
      as inhibin, in the regulation of gonadotrophin secretion.

PMID- 9278709
TI  - The petrosal ganglion of the adult cat: neuronal count, sectional area, and their
      respective distributions.
AB  - The petrosal ganglion contains most of the perikarya of sensory neurons of the
      glossopharyngeal nerve. We studied the number and size of neuronal somata in 4
      petrosal ganglia from adult cats. Ganglia were serially sectioned in length at 8
      microns, sections drawn through a projection microscope, and those neuronal
      profiles presenting nuclei and nucleoli on each section were counted and their
      areas measured. The number of neurons ranged from 2311 to 3429 (2908 +/- 271;
      mean +/- SEM). Neurons were symmetrically distributed around the longitudinal
      axes of most ganglia, with a skewed distribution in only one ganglion. The
      sectional area of most neurons (> 98%) ranged between 250 and 1725 microns 2,
      with median values of 667-963 microns 2. Area distributions were significantly
      different, but differences never exceeded 8.2% in related area bins. The ganglion
      presenting a skewed count distribution and the highest median area departed from
      the rest, with differences surpassing 25%. We conclude that the neuronal
      population of the petrosal ganglion of the cat is regular both with respect to
      the number and the size of its constituents, with departures from this pattern
      probably reflecting individual variations.

PMID- 9278710
TI  - Fimbria-fornix lesion impairs long-term potentiation in the dentate gyrus of the
      rat.
AB  - Bilateral aspiration lesions of the fimbria-fornix were performed in 10 male
      Sprague Dawley rats weighing 240-300 g under chloral hydrate narcose (420 mg/kg).
      Another 9 animals were operated in the same way, but no aspiration was carried
      out to constitute a control group. A week after surgery recording and stimulation
      electrodes were lowered to the dentate gyrus and the perforant path respectively,
      using the same narcose. After tetanic stimulation (10 trains at 400 Hz) a
      potentiation of the population spike develops in both groups, but the slope of
      the excitatory postsynaptic potential showed no potentiation in the lesioned
      group. Acetylcholinesterase histochemistry confirmed a severe reduction of the
      cholinergic innervation to the hippocampal formation, suggesting a causal
      relationship to the deficits seen in long-term potentiation. This impaired
      potentiation could be related to the memory deficits reported for fimbria-fornix
      lesioned rats. Such pattern of potentiation deviates from what has been described
      for aged, memory deficient rats, but closely corresponds to the changes described
      in infantile rats.

PMID- 9278711
TI  - A model of complete random molecular evolution by recurrent mutation.
AB  - A model for random molecular evolution based on recurrent mutation is proposed.
      Recurrent mutation replaces completely any original base in a nucleotidic site.
      This occurs if more than four times the number of reproductive cycles equal to
      the reciprocal of the mutation rate happen; no matter the population size, the
      number of nucleotides a genome has, or the taxa at which it belongs. The main
      results are: i) the expected distribution of DNA bases in a site is an
      isotetranomial distribution, where Adenine (A), Guanine (G), Cytosine (C) and
      Thymine (T) occur with probability equal to 0.25; ii) the distribution of bases
      in a site is independent from the distribution of bases in other sites. Several
      expected consequences that can be contrasted with actual data are generated.
      Species or operational taxonomic units (OTUs) that evolved in big populations
      should present distances equal to zero and similarities equal to one. OTUs
      evolving in small populations should present distances equal to 3/4 and
      similarities equal to 1/4. Thus, random molecular evolution by recurrent mutation
      cannot yield a tree at all. The only possible tree is that produced by random
      fluctuations of distances according to their variances (stochastic tree). Some
      consequences of the model on the expected primary structure of proteins are also
      analyzed. There are sufficient generations for any DNA segment evolving apart
      during the last four hundred million years, to reach those expected base
      distributions.

PMID- 9278712
TI  - Interactions that regulate the helical fold in proteins.
AB  - Several factors that may contribute to the stabilization of the helical structure
      in proteins, detected in studies made on short synthetic peptides, have been
      reported. Some of them are: presence of alanine or leucine, ionic-pair bonding,
      stabilization of the helical dipole moment by appropriate charges at the helix N-
      and C-caps, and aromatic interactions of amino acids located at positions i, i +
      4. An analysis of 54 helical structures from 12 proteins showed that all these
      stabilizing factors were also present in proteins, but the influence of any of
      them had a different weight, according to the distribution of the hydrophobic and
      hydrophilic amino acid residues in the helical sequence. The role of non-sequence
      depending interactions in helical stability, such as presence of disulfide
      bridges, or bonding of helical residues to substrate and/or cofactors, was also
      analysed.

PMID- 9278713
TI  - The effect of salinity on the growth and carotenogenesis in two Chilean strains
      of Dunaliella salina Teodoresco.
AB  - We studied the effect of salt concentration on the growth and carotenogenesis in
      two Chilean strains of Dunaliella salina, CONC-006 and CONC-007, cultivated in
      two media of different chemical composition J/l and PES, under controlled
      laboratory conditions. Growth rates, k (div day-1), intrinsic production rates of
      total carotenoids per unit time rcar (day-1), maximum levels of total
      carotenoids, K (mg l-1), and maximum production of total carotenoids per unit
      time, rK/4 (micrograms l-1 day-1) were estimated from growth and carotenogenesis
      data. The highest maximum productivity of total carotenoids was 978 micrograms l
      1 day-1 obtained in CONC-007 at 25% NaCl, and the lowest 15 micrograms l-1 day-1,
      in CONC-006 at 30% NaCl, both growing in PES medium. CONC-007 showed the highest
      growth rates, 0.76 and 0.65 div day-1, at the lowest salt concentration (5%) in
      PES and J/1, respectively. On the contrary, the strain CONC-006 exhibited a
      different growth pattern in both media. Its maximum growth rate in J/1 was 0.37
      div day-1 at 20% NaCl, and in PES, 0.53 div day-1 at 5% NaCl. According to these
      results, the best integration of growth and carotenogenesis in CONC-007 was
      obtained at 15% NaCl in J/1 from 10 to 25% NaCl in PES and in CONC-006, from 5 to
      20% NaCl in J/1 and from 5 to 10% NaCl in PES.

PMID- 9278714
TI  - Acetate enhances the chemosensory response to hypoxia in the cat carotid body in
      vitro in the absence of CO2-HCO3-.
AB  - To determine if intracellular acidosis enhances hypoxic chemoreception in the
      absence of CO2-HCO3- at pH 7.4, the effects of sodium acetate (30 mM) were
      studied on the chemosensory responses of the cat carotid body to hypoxic,
      stagnant and cytotoxic hypoxia. Carotid bodies were perfused and superfused in
      vitro with Tyrode's solution, free of CO2-HCO3-, buffered with HEPES-NaOH, pH
      7.40, at 36.5 +/d- 0.5 degrees C and equilibrated at PO2 of 125 Torr (perfusate)
      and < 20 Torr (superfusate). In the absence of acetate, hypoxia (PO2 25 Torr),
      flow interruption and NaCN (0.01-100 micrograms) augmented the chemosensory
      discharges. However, in the presence of acetate, the half-excitation time of
      these responses decreased and their amplitude increased. Thus, acetate enhances
      the chemosensory response to hypoxic, stagnant and cytotoxic hypoxia. It is
      suggested that that intracellular acidosis induced by acetate contributes to this
      potentiation by correcting the alkaline pHi caused by the absence of HCO3-(-)HCO2
      in the perfusate.

PMID- 9278715
TI  - New evidence of non seasonal factors in the menarche rhythm.
AB  - The phylogenetic, ontogenetic and seasonal hypotheses on the annual periodicity
      of menarche were tested. Data from European, Asian (Caucasian, Mongolian and
      Caucaso-Mongolian people from the northern hemisphere) and Chilean (Caucaso
      Amerindian from the southern hemisphere) populations were compared with data from
      Hungary (Caucaso-Mongolian Europeans from a northern temperature zone) and
      Madras, India (a complex ethnically originated people from a tropical northern
      area). Chileans were compared with those Caucaso-Mongolian people because
      Amerindians belong also to the Mongolian group. Hungarian girls showed peaks of
      menarche in the month of January (winter), June, July and August (summer), in
      contradiction with most European Caucasians who showed peaks only in winter
      months; and in agreement with Finns who showed both peaks. Indian girls had peaks
      in April, May and June (summer) and more extreme peaks and troughs than the
      Finnish girls (from a temperature arctic zone). These findings do not agree with
      the seasonal hypothesis, but they do with the phylogenetic hypothesis. Indian
      girls had a peak of menarche in the same month of birth and the arrangement of
      data according to the gestational-menarche coincidence showed a significant
      heterogeneity for the monthly peaks of menarche; thus, the ontogenetic hypothesis
      was also supported.

PMID- 9278716
TI  - Effect of policosanol on the hepatic cholesterol biosynthesis of
      normocholesterolemic rats.
AB  - We have suggested previously, measuring 14C-acetate incorporation into free
      cholesterol, that oral administration of policosanol inhibits hepatic cholesterol
      biosynthesis in rats. Nevertheless, since acetate has limitations to study
      cholesterol synthesis in vivo, we now investigate rates of incorporation of
      labeled water into hepatic sterol after policosanol treatment. Absolute rates of
      incorporation of 3H-water in sterols were depressed by policosanol by about 20%,
      giving a more accurate degree of cholesterol biosynthesis inhibition in this
      species. Since policosanol did not inhibit labeled mevalonate incorporation into
      cholesterol in rat liver, we also studied the effect of policosanol on hydroxy
      methylglutaryl-coenzyme A (HMG-CoA) reductase. Reductase activity assayed in
      microsomes treated with policosanol remained unchanged, suggesting that
      cholesterol synthesis is not inhibited by a direct action of policosanol on this
      enzyme.

PMID- 9278717
TI  - Maintenance of hypothalamic GnRH release during lactation in the rat: a push-pull
      perfusion study.
AB  - The activity of the gonadotropin-releasing hormone (GnRH) pulse generator during
      lactation was assessed by direct determination of GnRH levels impinging upon the
      pituitary gland. Sprague-Dawley rats were implanted on day 15 of pregnancy with a
      push-pull perfusion cannula directed to the anterior pituitary. All implanted
      animals showed normal parturition, maternal behavior and lactation. Push-pull
      perfusions were performed in 15 rats suckling 11.0 +/- 0.8 pups (range 4-15) on
      day 7-20 of lactation and repeated on diestrous 1 after weaning in some of the
      same animals. GnRH content of the samples was assayed by RIA. GnRH pulses were
      clearly detected during lactation. Mean GnRH secretion rate was 1.9 +/- 0.3 pg/10
      min (chi +/- SE, range between 0.5 and 3 pg/10 min) and interpulse interval was
      37.5 +/- 1.7 min (range between 27 and 50 min). There was a significant decrease
      of about 19% in the interpulse interval after weaning. There was no significant
      difference in GnRH pulse amplitude nor in GnRH secretion rate between lactation
      and diestrous. These results demonstrate that nursing does not suppress the GnRH
      pulse generator in the rat.

PMID- 9278718
TI  - Modelling the activity of the Ultrabithorax parasegment-specific regulatory
      domains around their anterior boundaries.
AB  - The Drosophila Ultrabithorax (Ubx) gene was one of the first homeotic genes to be
      characterised and it specifies the phenotypic characteristics of parasegments 5
      and 6. The intricate pattern of Ubx expression in these parasegments is conferred
      by enormous regulatory regions which, together with the structural gene,
      constitute the Ubx domain. A genetic, "open-for-business", model based on
      classical mutational analysis proposed that the regulatory regions were in fact
      composite structures, consisting of parasegment-specific regulatory domains that
      contain arrays of cell-specific enhancers which drive the intricate pattern of
      Ubx expression. Here, we propose a molecular mechanism, based on a survey of
      numerous transgenic studies, of the setting up of these parasegment-specific
      regulatory domains in the appropriate parts of the late blastoderm embryo. We
      construct a mathematical model of this mechanism using the molecular
      characteristics of a single initiator element, the distributions of segmentation
      gene products and simple competitive binding equations. We attempt to fit this
      mathematical model to the idealised patterns of activity and closure of the
      parasegment-specific domains derived from the genetic model. The resulting fitted
      pattern of activity and closure obtained with the simplest version of our
      competitive binding model shows some deviations from the idealised pattern based
      on the genetic model. Comparison of the predictions with recent experimental
      evidence suggests that the competitive binding model more accurately reflects
      certain features of the Ubx expression pattern--features not predicted by the
      genetic model.

PMID- 9278719
TI  - Models for pairing of IS10 encoded antisense RNAs in vivo.
AB  - Antisense regulation of IS10 transposase synthesis is mediated by a small RNA
      molecule, RNA-OUT which is complementary to the 5' region of the IS10 transposase
      mRNA, RNA-IN. Pairing between the two species in vivo prevents initiation of RNA
      IN translation by steric occlusion of the ribosome binding site. The goal of this
      work is to develop a mathematical basis for antisense repression in vivo. Thus,
      by modeling antisense pairing as a biomolecular reaction in vivo, I have
      developed equations which relate the degree of translation inhibition to a
      relative pairing rate constant, k, and the in vivo RNA-OUT concentration. Using
      the methodology developed here, an analysis of mutations in the first three 5'
      bases of RNA-IN reveals a semi-logarithmic relationship between k and delta G,
      the estimated change in the free energy of pairing. Such correlations are not
      observed for mutations at other positions, implicating only the first three 5'
      bases of RNA-IN in the formation of a pairing nucleus with RNA-OUT. Finally, an
      analysis of mutations that affect antisense action at a post-nucleation step has
      been undertaken here and a specific model for how these mutations may affect
      antisense pairing is discussed.

PMID- 9278720
TI  - Escape from evolutionary stasis by transposon-mediated deleterious mutations.
AB  - Evolution within a rugged fitness landscape is limited by the tendency for
      organisms to become trapped on local optima resulting in evolutionary stasis. It
      is presently unclear how founder populations escape from an adaptive peak to
      found a new species. Insertion sequences, transposons and other mobile DNA
      elements are found in all species of eukaryotes, bacteria and archaebacteria,
      where they have been sought and are usually considered to be genomic parasites or
      selfish genes. However, many transposons and other mobile repetitive DNA are
      remarkably species or phyla-specific, indicating that infection with transposable
      elements coincides with speciation events and is involved in promoting
      evolutionary change. We propose here a model in which transposable elements are
      involved in speciation events by their ability to produce irreversible
      deleterious mutations that promote escape from evolutionary stasis. We have
      constructed a genetic algorithm designed to model both spontaneous and transposon
      mediated mutations in populations of asexual digital organisms. We use this model
      to investigate the effect of transposon-mediated mutations on the rate of
      evolution of digital organisms as they compete for resources within an artificial
      adaptive landscape. In the absence of transposon mutations the seed organisms
      quickly evolve to occupy the nearest adaptive peak but thereafter evolutionary
      stasis ensues and adjacent empty peaks are left unoccupied. In the presence of
      transposon mutations, evolution is again dominated by stasis but is punctuated by
      bursts of rapid evolution in with consecutive unoccupied adaptive peaks are
      filled with organisms derived from single transposition events. Rapid
      evolutionary events leading to founding of new biological species, may be
      similarly initiated by irreversible deleterious mutations induced by
      transposition.

PMID- 9278721
TI  - Sperm competition games: inter- and intra-species results of a continuous
      external fertilization model.
AB  - We investigate the relationship between sperm competition intensity and sperm
      expenditure, both across species and within a species, using a two sperm
      competition models. In model 1, the males cannot assess the number of
      competitors, and their ejaculate effort is shaped by the average number <N> of
      competitors. In model 2, males can assess the number Ni of competitors at each
      spawning exactly. Males can vary the mass m of their sperm and the number si at a
      spawning. The aim is to find the evolutionarily stable strategies and hence the
      way that m and si vary with Ni. A continuous fertilization model in which the
      sperm have to swim in order to fertilize an egg is described. This is used to
      find simultaneous equations describing m and si. These are solved numerically.

PMID- 9278722
TI  - A theory of metabolic costs for bipedal gaits.
AB  - A simple model predicts the energy cost of bipedal locomotion for given speed,
      stride length, duty factor and shape factor. (The duty factor is the fraction of
      stride duration, for which a foot is on the ground, and the shape factor
      describes the pattern of force exerted on the ground). The parameters are varied
      to find the gait that minimizes metabolic energy cost, for each speed. A previous
      model by Alexander calculated the work that muscles have to do, but the metabolic
      cost (calculated in this paper) is more likely to be the principal criterion for
      gait selection. This model gives good predictions of human stride lengths, and of
      the speed at which we break into a run. It predicts lower duty factors and higher
      shape factors than are normally used, but the relationships between these gait
      parameters and speed parallel the empirical relationships.

PMID- 9278723
TI  - A theoretical approach to the bell-shaped dependency of cell proliferation on the
      hormone concentration.
AB  - Binding of human growth hormones (hGH) to the receptors was studied with a
      theoretical, molecular-level model. An hGH has two sites bindable to different
      receptors with different binding energies. In the model the hGHs diffusively
      moved in a box (i.e. the volume of solution), and receptors on the bottom face
      the box (i.e. a membrane). The system consisted of a number of hGHs and
      receptors, which could form hGH-[receptor]2 or hGH-receptor complexus. In a
      complex, small inter-molecular positional fluctuations were allowed with keeping
      the inter-molecular binding. Partition function of the system was calculated. In
      a low hGH-concentration range, free receptors were dominant on the membrane; in a
      medium concentration range, hGH-[receptor]2 complexus, which induce cell
      proliferation, were dominant, and in a high concentration range, hGH-receptor
      complexus, which inhibit the proliferation, were dominant. This dependency (bell
      shaped dependency) of formation of hGH-[receptor]2 complex on the hGH
      concentration agreed well with experimental observation. The values of EC50 (hGH
      concentration at that the cell-proliferation rate rose to 50% of the maximum rate
      by the formation of hGH-[receptor]2 complexus) and IC50 (hGH concentration at
      that the proliferation rate decreased to 50% of the maximum by the formation of
      hGH-receptor complexus) from my method were 18 pM and 2.2 microM, respectively.
      By calculating thermodynamic quantities (i.e. entropy and enthalpy), factors that
      determine the bell-shaped dependency were obtained. At the medium concentration,
      the entropy of free hGHs played an important role in stabilizing the hGh
      [receptor]2 complex. Small changes in binding energies or in inter-molecular
      positional fluctuations largely changed the dependency of the complex formation
      on the hGH concentration. This method is useful in explaining the experimental
      results that small molecular modification largely changes the formation of the
      complex.

PMID- 9278724
TI  - The role of inter-cellular adhesion in the recirculation of T lymphocytes.
AB  - We refine an existing model of T lymphocyte recirculation, in order to
      incorporate a description of the adhesion between T cells and other cell types in
      the lymphoid tissue, such as dendritic cells. The new model is able to fit the
      animal experiments on lymphocyte recirculation. It also allows for the variation
      of these adhesive properties, as would occur in the presence of antigen, and it
      is shown that it is possible for the T cell counts in blood to reach very low
      levels, as a result of increased adhesion between T cells and dendritic or other
      cells present in the lymphoid tissue. We discuss the implications of this
      phenomenon for HIV infection.

PMID- 9278725
TI  - Coevolutionary chase on exploiter-victim systems with polygenic characters.
AB  - I study the dynamics of a simple quantitative genetic model describing
      coevolution of two antagonistic species of the victim-exploiter type. In this
      model, individuals are different with respect to an additive polygenic character
      that is under direct stabilizing selection and which also determines the strength
      of within and between species interactions. The model assumes that between
      species interactions are most intense when the victim's and exploiter's
      phenotypes match. I show that a cyclic coevolutionary chase is possible under a
      broad range of conditions. In most cases, the system cycles if the "victim" has a
      stronger incentive to win and/or a larger genetic variance, and is under stronger
      stabilizing selection than the "exploiter". The results presented here provide
      counter-examples to recent studies that (1) question the applicability of "Red
      Queen" and "arms race" metaphors for continuously varying traits; (2) argue for
      the existence of crucial differences between major and minor loci dynamics; and
      (3) attribute a stabilizing role to coevolution.

PMID- 9278726
TI  - Future directions in preventing child abuse.

PMID- 9278727
TI  - Child abuse and neglect from an indigenous Australian's perspective.

PMID- 9278729
TI  - Simplifying child sexual abuse data management: from medical record to computer.
AB  - This article presents a model approach for child sexual abuse data management for
      centers that provide medical evaluations of suspected sexual abuse victims. The
      uses and advantages of this system are summarized and an example data entry form
      is provided. Information and guidelines for developing a computer database and
      for efficient entry of the data by clinical personnel are outlined.

PMID- 9278728
TI  - Reimbursement and insurance coverage in cases of suspected sexual abuse in the
      emergency department.
AB  - OBJECTIVE: To characterize third party payor types and rates of reimbursement for
      hospital costs in emergency department (ED) evaluations of preadolescents
      presenting as suspected victims of sexual abuse (SSA). DESIGN AND METHODS:
      Retrospective chart review, comparing a set of 186 SSA patients with 623
      evaluated for upper limb fracture and cumulative reimbursement and insurance data
      for all patients presenting to the ED during a 12-month period. RESULTS: A
      greater percentage of SSA patients was uninsured (N = 96, 52%) as compared to
      patients with fractures (N = 9, 1%); 23% of all ED billing came from the
      uninsured. Of the 96 self-pay SSA patients' bills only 4% reimbursement was
      received. Of the insured, a greater percentage of the SSA patients was covered by
      publicly-funded plans (n = 59, 66%) as compared to fracture patients (N = 327,
      52%). A lower percentage of insured SSA bill reimbursement was received from
      publicly-funded insurance than from commercial insurance (28% vs. 58%).
      CONCLUSIONS: Hospital costs of SSA patients are more often and to a greater
      degree underwritten by the hospital itself as a result of lower reimbursement and
      a higher percentage of uninsured and publicly-funded plans in that group, raising
      critical questions about how care for children with serious socially-based
      diagnoses is delivered and funded.

PMID- 9278730
TI  - Evolution of the cranial computed tomography scan in child abuse.
AB  - Computed tomography (CT) scans obtained at the time of clinical presentation have
      occasionally been reported to be normal in children with history and findings of
      significant abusive head injury. We have retrospectively observed abnormalities
      in "normal" scans of some similar children. We have also seen abnormalities
      develop on serial scanning. To determine how frequently these situations occur,
      we reviewed charts of 34 children with a final diagnosis of child abuse who also
      had cranial CT scans performed. Their CT scans were retrospectively reviewed by a
      pediatric radiologist. Eleven (11/34) CT scans had initially been interpreted as
      normal. Four (4/11) of these had been reinterpreted during the hospitalization as
      abnormal, affecting medical (1) and legal (3) outcome. Repeat scanning in three
      of the remaining seven resulted in surgical drainage of a subdural effusion (1)
      and affected legal outcome (2). Four of the seven initial scans felt normal
      throughout the hospitalizations were judged abnormal on retrospective review.
      This evaluation was confirmed in the two rescanned. Initial CT interpretation
      most often failed to appreciate changes in parenchymal density and small amounts
      of falcine or cortical subdural blood. Subsequent scans also showed evolving
      effusions and infarcts. Changes were noted in 1 1/2 to 5 days. The CT scan
      frequently shows subtle changes in the immediate posttrauma period. If the child
      does not recover promptly, subsequent scans frequently result in significant
      changes in clinical and legal management.

PMID- 9278732
TI  - Child maltreatment: the United States Air Force's response.
AB  - Families in the military are not immune to problems of child abuse and neglect,
      but few data have been disseminated which describe child maltreatment in the
      military. This article reports on the incidence of child maltreatment in the
      United States Air Force by presenting descriptive data on over 19,587
      substantiated cases of child abuse and neglect which occurred over a 6-year
      period. Annual percentage increases in child maltreatment reports are discussed,
      as are substantiation rates for child abuse and neglect. This article also
      describes the United States Air Force programs serving military personnel and
      their families throughout the world. A subset of cases are analyzed and
      offenders' and spouses' perceptions of the services received and the benefits
      derived are reported.

PMID- 9278731
TI  - The measurement of psychological maltreatment: early data on the Child Abuse and
      Trauma Scale.
AB  - This paper describes a self-report measure, the Child Abuse and Trauma Scale,
      which yields a quantitative index of the frequency and extent of various types of
      negative experiences in childhood and adolescence. Data on this measure are
      presented for two large samples of college students and for a small clinical
      sample of subjects with a diagnosis of Multiple Personality Disorder. The strong
      internal consistency and test-retest reliability of the scale in the college
      population is documented, and its validity is attested to by demonstrating that
      it correlates significantly with outcomes such as dissociation, depression,
      difficulties in interpersonal relationships, and victimization, all of which have
      previously been associated with childhood trauma or abuse. The extremely high
      scores of the Multiple Personality subjects confer additional validity to the
      measure. The authors suggest that the construct of psychological maltreatment
      underlies the destructive elements of numerous forms of abuse and neglect, and
      that the scale they have developed may provide a useful index of this construct.

PMID- 9278733
TI  - Childhood sexual abuse and current suicidality in college women and men.
AB  - In previous research, adults who reported childhood sexual abuse have been more
      suicidal than nonabused adults, but no research has examined their cognitive
      deterrents to suicide. Strict definitions of sexual abuse in these studies have
      excluded (a) unwanted sexual experiences with peers, and (b) exploitive
      experiences not involving genital contact (i.e., unwanted sexual invitations or
      suggestions, unwanted exposure to others' genitals via exhibitionism, unwanted
      kissing or hugging in a sexual way). The present study compared suicidal behavior
      and cognitive deterrents to suicide in 266 college students using both a strict
      and a liberal definition of sexual abuse. Both women and men abused by adults or
      peers were more suicidal as adult college students than were women and men with
      no such history. Women reported similar degrees of suicidality as men, but
      greater survival and coping beliefs and more fear of suicide. Those whose sexual
      abuse involved touching were more suicidal, and felt less able to cope, and less
      responsibility for their families, than nonabused adults. Implications are that
      adults who experienced childhood sexual abuse that involved touching are more
      suicidal and have less cognitive deterrents to suicide than adults who have not,
      regardless of whether they are men or women or whether they were abused by adults
      or by peers.

PMID- 9278734
TI  - Assessment of fairness in child custody decisions.
AB  - Court-appointed child advocates, attorneys, guardians ad litem, and therapists
      were asked to rate preferred traits for mothers and fathers, and to make custody
      decisions and abuse likelihood ratings for children in one of two vignettes that
      varied only as to whether mother or father was described as incompetent to parent
      without threat of further abuse. Results revealed that this sample of
      professionals did not hold double standards with respect to attributes important
      for mothers versus fathers. To the contrary, interpersonal sensitivity traits,
      traditionally identified as most prevalent among women, were valued equally in
      mothers and fathers and preferred for both parents to interpersonal potency,
      traditionally ascribed more readily to men. Further, decisions about custody and
      placement or abuse likelihood were not affected by any sex-role stereotypes
      professionals held about parents, nor by professionals' gender or specific
      occupation. The only factor that affected custody judgments and abuse likelihood
      ratings was the competence of the parent in question. These findings suggest that
      biases with regard to gender to gender or traditional sex-role preferences for
      parents are disappearing among professionals who make important placement
      decisions in the lives of abused children. Future studies must assess whether
      these theoretical findings translate into actual behavior in real-life abuse
      cases for the professional groups represented in this sample.

PMID- 9278735
TI  - Child maltreatment: the collaboration of child welfare, mental health, and
      judicial system.
AB  - The alliance of child welfare, mental health, and legal systems has received
      little empirical attention, despite the magnitude of its impact on children and
      families. We examined the congruence of child protection agencies legal
      positions, court clinic recommendations, and judicial dispositions in a sample of
      59 contested child maltreatment cases. Placement recommendations/decisions among
      all three systems were highly correlated, although the relationship was not so
      strong as to undermine the independence of any one system. Where there was
      disagreement between successive evaluations, it was in the direction of enhancing
      family integrity and parental access rights. We advanced three hypotheses to
      account for our findings: (a) changes in successive recommendations reflect the
      increasing sophistication of the assessment process; (b) changes reflect
      increasing distance from the family's ecology and are therefore increasingly ill
      informed; and (c) the changes are purely probabilistic, reflecting a drift toward
      the societal status quo.

PMID- 9278736
TI  - A cluster analysis of detected and substantiated child maltreatment incidents in
      rural Colorado.
AB  - This paper reports the results of a cluster analysis of the incidents of detected
      and substantiated child maltreatment in 31 rural Colorado counties during the 5
      year period (1986-1990). Mapping and statistical techniques employed revealed
      time-space clustering in the occurrence of child abuse and neglect in sparsely
      settled rural areas of the state. The study examined temporal-geographic patterns
      among all 830 confirmed incidents in the Colorado Child Abuse and Neglect
      Registry for counties of less than 10,000 population. These findings suggest that
      a first incident of abuse or neglect serves as a sentinel event, predicting a
      period of more frequent receipt and substantiation of maltreatment cases by child
      protection professionals in the county or community of occurrence. Clustering was
      apparent using 3-, 7-, 14-, 30-, and 60-day intervals of time; a scheme endorsed
      by the Centers for Disease Control for national study of the epidemicity of
      adolescent suicide. An agenda is proposed to review the appropriateness and
      adequacy of child protection policies and protocols in view of this phenomenon,
      and to pursue additional related research objectives.

PMID- 9278737
TI  - The effects of disclosure and intervention on sexually abused children.
AB  - There has been concern that disclosure and intervention might negatively impact
      victims of sexual abuse. In this retrospective study, 82 children and their
      families were interviewed about their experiences with disclosure and
      intervention an average of 3.5 years later. The children and parents completed a
      measure of distress developed for the study which discriminated between abused
      and non-abused children. The children reported primarily favorable experiences
      and provided clinically helpful descriptions of the positive and negative aspects
      of intervention. More contacts with intervention professionals was associated
      with increased distress, placement, offender removal and testifying were not.
      Based on the children's comments, suggestions for improving the intervention
      process are made.

PMID- 9278738
TI  - Interobserver differences in interpretation of physical signs in sexual abuse.

PMID- 9278739
TI  - Hallux valgus in men: effect of the distal metatarsal articular angle on hallux
      valgus correction.
AB  - The results of hallux valgus correction were reviewed for 34 male patients (41
      feet). The severity of the preoperative deformity determined the operative
      technique of correction. A distal soft tissue procedure with proximal first
      metatarsal osteotomy was performed in 30 patients (35 feet) with an average
      correction of the hallux valgus angle of 22 degrees. A chevron procedure was
      performed in five cases and a McBride procedure in one other case, all with less
      severe deformities. Complications included one deep wound infection, one broken
      screw at the metatarsal osteotomy site, and three cases of hallux varus. No
      patients underwent reoperation. Undercorrection was noted in 10 of 35 cases (29%)
      where a distal soft tissue procedure with proximal first metatarsal osteotomy was
      performed. A nonsubluxated (congruent) metatarsophalangeal (MTP) joint associated
      with a hallux valgus deformity was present in 15 of 41 (37%) of all cases and 10
      of 35 (29%) of cases that underwent a distal soft tissue procedure with proximal
      metatarsal osteotomy (DSTR with PMO). A subluxated (noncongruent) MTP joint
      associated with hallux valgus was present in 26 of 41 (63%) of all cases and 25
      of 35 (71%) of cases undergoing a DSTR with PMO. There was a highly significant
      difference in the average distal metatarsal articular angle (DMAA) as measured in
      the nonsubluxated (congruent) MTP joints (20.7 degrees) and the subluxated
      (noncongruent) MTP joints with hallux valgus (10 degrees) (P = 0.0001). The
      average distal metatarsal articular angle for all cases undergoing DSTR with PMO
      was 13 degrees. When the postoperative hallux valgus angle was compared with
      DMAA, the average residual hallux valgus angle was 10.1 degrees. With a
      subluxated (noncongruent) first MTP joint with hallux valgus (a low DMAA), the
      percent of hallux valgus correction (hallux valgus correction [in
      degrees]/preoperative hallux valgus deformity [in degrees]) was 77%. In patients
      with a nonsubluxated (congruent) first MTP joint with hallux valgus (a high
      DMAA), the percent correction was 46%, an almost twofold difference in percent
      correction. There was a close correlation between the preoperative DMAA and the
      postoperative hallux valgus angle in both the subluxated and congruent subgroups
      (P = 0.0003). With an intra-articular repair (a DSTP with PMO), the magnitude of
      correction of a hallux valgus deformity is limited at the MTP joint by the distal
      metatarsal articular angle.

PMID- 9278740
TI  - Pathologic anatomic variations in subtalar anatomy.
AB  - Thirteen patients presenting with symptomatic pathologic variations or congenital
      deformities of the subtalar joint are presented. These variations included: four
      abnormal posterior talar processes, five patients with asymmetric subtalar joint
      development, and four congenital complete subtalar coalitions with a secondary
      ball-and-socket joint. In each case these adult patients had been unaware of the
      variation and had been symptom free until "awakening" sprain or fracture trauma
      brought about symptoms. The nonoperative and operative management of these
      variations is reviewed.

PMID- 9278741
TI  - Combination chevron plus Akin osteotomy for hallux valgus: should age be a
      limiting factor?
AB  - Current literature consistently precludes the chevron osteotomy for bunion
      correction in patients older than age 50 years. We retrospectively reviewed 47
      patients (73 bunions) with an average age of 62 years (range, 55-81 years old)
      who had a chevron-Akin double osteotomy. The mean follow-up was 4 years, 6 months
      (range, 2 years, 3 months to 8 years, 2 months). The overall satisfaction rate
      was 95%. No significant pain or stiffness in the first metatarsophalangeal joint
      occurred in comparison with other bunion procedures. Radiographic results were
      better for patients with a preoperative intermetatarsal angle of less than 15
      degrees and tibial sesamoid position of less than or equal to 2. We disagree with
      the current recommendation that age older than 50 years is a contraindication to
      a chevron procedure. The Akin osteotomy adds additional intraoperative correction
      of the hallux angulation and rotation; thus, the chevron-Akin double osteotomy is
      a useful combination procedure. We recommend this procedure for the mild to
      moderate bunion deformity even in elderly patients.

PMID- 9278742
TI  - Stress radiography and stress examination of the talocrural and subtalar joint on
      helical computed tomography.
AB  - The main objective of this study was to compare subtalar inversion stress views
      using the Broden view with inversion stress views on helical computed tomography
      (CT). One of the drawbacks of routine radiography is the imaging of three
      dimensional structures in a two-dimensional plane. We investigated whether the
      use of helical CT would lead to a more objective and clearer measurable method to
      determine the amount of tilt in the subtalar joint. A group of 15 patients with
      unilateral chronic instability complaints and clinically suspected subtalar
      instability was examined. The contralateral asymptomatic foot was used as
      control. A variable amount of subtalar tilt (range, 4 degrees to 18 degrees) was
      demonstrated in all cases on stress radiographs, without finding significant
      difference between the symptomatic and asymptomatic feet. However, contrary to
      the findings at the talocrural level, subtalar tilt was found in none of the
      patients using helical CT. Thus, we now doubt that the tilt seen during stress
      examination using the Broden view is the true amount of tilt. It may be that the
      lateral opening, seen on these radiographs, largely results from imaging two
      planes that have made a translatory and rotary movement relative to each other in
      an oblique direction. It is concluded that the Broden stress examination might
      not be useful for screening patients with subtalar instability. Associated
      anomalies not visible on the radiographs were detected by helical CT. In four
      cases, narrowing of the articular cartilage and irregular and hypertrophic bone
      formation at the middle facet joint of the subtalar joints were found. It is
      likely that these changes cause disturbance of function of this joint and it is
      suggested that the subjective complaint of instability with "giving way" is not
      only caused by hypermobility, but can be caused by other disturbance of normal
      motion.

PMID- 9278743
TI  - Clinical and radiographic outcome of revision surgery for failed triple
      arthrodesis.
AB  - Between 1987 and 1994, we treated 33 patients with surgical revision for failed
      triple arthrodesis, 28 (29 feet) of whom returned for final examination (mean,
      4.4 years; range, 2-7 years). The average age of these 16 women and 12 men was 46
      years (range, 14-69 years). Before the revision procedure, patients had undergone
      nonoperative therapies for an average of 3.7 years (range, 0.5-12 years) and an
      average of three foot operations (range, 1-6 operations) after the primary triple
      arthrodesis. All patients were managed with rigid internal fixation via
      cannulated screws and power staples. Calcaneal osteotomy and/or revision of the
      transverse tarsal arthrodesis via appropriate saw cuts and bone wedges were used.
      Iliac crest bone graft was added, when a bone block arthrodesis was required, for
      those patients with nonunion or ankle impingement. Arthrodesis was achieved in
      all 29 feet, although 4 patients (4 feet) (14%) required additional procedures
      for malunion (2 patients), deformity recurrence (1 patient), deep infection (1
      patient), and skin graft (1 patient). Comparison of the average pre-
      (retrospective) and postoperative American Orthopaedic Foot and Ankle Society 94
      point hindfoot and ankle scores showed a significant improvement: 31 points
      (range, 13-61 points) versus 59 points (range, 24-91 points), respectively (P <
      0.05). On a scale of 0 to 10 points, average patient satisfaction was 7.8 points
      (range, 2-10 points). This study demonstrated a satisfactory improvement in
      patient outcome after surgical correction of failed triple arthrodesis. We
      conclude that such a revision, although complex, may be attempted to establish a
      plantigrade foot free of infection and able to wear shoes without and orthosis or
      brace.

PMID- 9278744
TI  - Effect of proximal phalangeal epiphysiodesis in the treatment of macrodactyly.
AB  - The recommended treatment for macrodactyly of the foot will often include
      epiphysiodesis of the proximal phalanx in an attempt to halt further longitudinal
      growth of the toe. Nine patients who underwent open epiphysiodesis and debulking
      of the excess soft tissues involving 11 toes were reviewed to evaluate the
      effectiveness of this procedure. In 9 of 11 toes, overall length of the proximal
      phalanx did not change after surgery. Two toes demonstrated continued growth; one
      of these toes underwent a repeat epiphysiodesis of the phalanx, and the other
      foot underwent epiphysiodesis of the affected metatarsal. Overall, this surgical
      approach led to radiographic results that satisfied the surgical goals.

PMID- 9278745
TI  - Pigmented villonodular synovitis in the first metatarsophalangeal joint:
      arthroscopic treatment of an unusual condition.
AB  - Pigmented nodular synovitis is an uncommon condition of the foot. In this case
      history, we report a case of pigmented nodular synovitis in the first
      metatarsophalangeal joint, treated by arthroscopic synovectomy. Pigmented nodular
      synovitis to our knowledge has not been described in the first
      metatarsophalangeal joint. We report successful treatment of the condition by
      arthroscopic removal of the tissue, with the patient being asymptomatic 2 years
      after surgery.

PMID- 9278746
TI  - Achilleo-calcaneal vascular network.
AB  - This study investigates the vascularization of the Achilles tendon in 32 lower
      limbs of human neonates by injecting colored latex with subsequent
      microdissection. Because of its biomechanical significance (achilleo-calcaneal
      plantar system) and the lack of descriptions in the literature, we analyzed the
      vascularization of the attachment area in the calcaneus, describing the achilleo
      calcaneal vascular network, which is always well supplied in contrast to other
      tendinous areas.

PMID- 9278747
TI  - Action of the peroneus longus tendon on the first metatarsal against metatarsus
      primus varus force.
AB  - A medially directed force was applied to the first metatarsal in 10 cadaver feet.
      The peroneus longus tendon was subjected to a pull of 5 pounds. The soft tissues
      between the first and second metatarsals were cut sequentially, starting with the
      skin on the dorsal and plantar aspect, followed by the intermetatarsal ligament
      and adductor hallucis tendon, and, finally, the peroneus longus tendon at its
      distal insertion. Dorsoplantar radiographs while weightbearing were taken after
      each sectioning. A statistically significant varus displacement of the first
      metatarsal was observed only after transection of the peroneus longus tendon. It
      was concluded that the peroneus longus tendon is a strong retaining mechanism of
      the first metatarsal.

PMID- 9278749
TI  - Surgically documented rupture of the plantaris muscle: a case report and
      literature review.

PMID- 9278748
TI  - Ankle fractures involving the fibula proximal to the distal tibiofibular
      syndesmosis.
AB  - Thirty-two cases of ankle fractures associated with fibular fractures above the
      distal tibiofibular syndesmosis were studied. All were treated with open
      reduction and internal fixation. The average follow-up was 25 months. The results
      of the postoperative evaluation were rated, based on subjective clinical
      criteria, as good, fair, and poor. According to the Lauge-Hansen classification,
      there were 17 (53%) cases of supination-external rotation injury (2 stage 2 and
      15 stage 4), 9 (28%) cases of stage 3 pronation-abduction injury, and 6 (19%)
      cases of pronation-external rotation injury (3 stage 3 and 3 stage 4). All cases
      could be classified as Weber type C or as suprasyndesmotic, fibular diaphyseal
      fracture (44-C) according to the Orthopaedic Trauma Association classification.
      In 18 (56%) cases, the fracture was associated with ankle dislocation. There were
      seven (22%) open fractures, (two grade I, four grade II, and one grade IIIA).
      Syndesmotic screws were used in 23 (72%) cases (12 supination-external rotation
      injury, 6 pronation-external rotation injury, and 5 pronation-abduction injury).
      The syndesmotic screw was removed after an average of 9 weeks. Four (13%)
      nonunions and two (6%) delayed unions of the fibula were treated with bone
      grafting and/or hardware revision and eventually healed. Three of the nonunions
      had poor clinical results because of degenerative ankle joint arthritis in two
      (one of them ended in arthrodesis) and deep infection, which was eventually
      cured, in the third. The fourth nonunion had a fair result. One of the delayed
      unions had a fair result (an obese patient) and the other had a good result. Two
      patients developed deep infections; one ended in gangrene and amputation in a
      diabetic patient, and the other was a patient with fibular nonunion that
      eventually healed. Three patients had superficial infections that were treated
      successfully. Of the 32 cases, 23 (72%) showed good results, 4 (13%) showed fair
      results, and 5 (16%) showed poor results. The cases with poor results included
      three fibular nonunions, one deep infection, and one recurrent superficial
      infection and wound dehiscence after hardware removal. A syndesmotic screw is
      usually needed in cases of fracture-dislocations. Two patients with occult
      fibular nonunions developed diastasis of the syndesmosis after removal of the
      syndesmotic screw. It was found that reduction and temporary pinning of the
      distal tibiofibular joint helps achieve fibular length, which is crucial to
      restoring the biomechanics of the ankle joint. It seems advisable not to remove
      the syndesmotic screw until there are signs of healing of fibular fracture to
      avoid diastasis of the distal tibiofibular joint. Bone grafting should be
      considered in high energy fractures with comminution. These complex injuries are
      associated with higher rates of complications. Poor results can be attributed to
      fracture factors, e.g., open fractures, infections; patient factors, e.g.,
      obesity, lowered immunity as in diabetes, and noncompliance; and iatrogenic
      factors, e.g., early removal of syndesmotic screws.

PMID- 9278751
TI  - Footwear prescriptions.

PMID- 9278752
TI  - Treatment outcome for 424 primary cases of clinical I cutaneous malignant
      melanoma of the head and neck.
AB  - BACKGROUND: Cutaneous malignant melanoma (CMM) is increasing in frequency.
      Surgery remains the primary and only curative treatment method. Our aim was to
      define prognostic factors and outcome predictors for patients with clinical stage
      I CMM of the head and neck. METHODS: Surgical treatment and outcome was analyzed
      for 424 patients with clinical stage I melanoma of the head and neck, completing
      initial treatment at the Mayo Clinic (1970-1990). The data were analyzed using
      the Kaplan-Meier product-limit method and Cox multiple-regression models.
      RESULTS: Overall, 180 (42%) patients underwent elective lymph node dissection
      (ELND) as part of the initial treatment; occult disease was demonstrated in 15
      (8.3%). Among patients with tumor > 1.5 mm thick, occult regional disease was
      found in 15%. Failure of final treatment occurred in 152 (36%). Overall, 82% and
      75% of the patients survived 5 and 10 years, respectively. CONCLUSIONS: Tumor
      thickness, extent of invasion, and the presence of occult region metastatic
      disease were the only independently predictive value (p < .005) of recurrence.
      The detection of disease by ELND did not appear to protect the patient from
      disease progression but identified those with regionally advanced disease and
      highest risk for recurrence. The development of recurrence significantly reduced
      but did not eliminate the potential for extended disease-free survival with
      subsequent treatment.

PMID- 9278750
TI  - Pseudoaneurysm with an arteriovenous fistula of the tibial vessels after plantar
      fasciotomy: a case report.

PMID- 9278754
TI  - Are head and neck specific quality of life measures necessary?
AB  - BACKGROUND: The purpose of this study was to determine whether head and neck
      specific health status domains are distinct from those assessed by general
      measures of quality-of-life (QOL). METHODS: Cross-sectional study of 55 head and
      neck cancer patients in tertiary academic center was made. Three head and neck
      specific measures,-including the Head & Neck Survey (H&NS); a brief, multi-item
      test which generates domain scores; and a general health measure,-were
      administered. RESULTS: The H&NS was highly reliable and more strongly correlated
      to the specific measures than to the general measure. Eating/swallowing (ES) and
      speech/communication (SC) were not well correlated with general health domains.
      Head and neck pain was highly correlated to general bodily pain (0.88, p <
      .0001). Despite correlations to some general health domains, appearance (AP) was
      not fully reflected by any other domain. CONCLUSIONS: Head and neck-specific QOL
      measures are necessary and should include domains that reflect ES, SC, and AP.

PMID- 9278753
TI  - Quality of life of disease-free survivors of advanced (stage III or IV)
      oropharyngeal cancer.
AB  - BACKGROUND: This study assessed the quality of life (QOL) of patients with
      advanced oropharyngeal cancer (stage III or IV) who were disease-free at 1 year
      posttreatment. METHODS: Between 1993 and 1994, 13 consecutive cases were
      identified from the University of Washington QOL registry. Patients were divided
      into two groups, depending on treatment: surgical group, 6 patients treated with
      surgical resection and postoperative radiotherapy; and nonsurgical group, 7
      patients treated with definitive radiotherapy. RESULTS: Composite pretreatment
      and posttreatment QOL scores were similar for the two treatment groups. Subset
      analysis of QOL domains revealed that both treatment groups generally reported a
      worsening of chewing and swallowing. A worsening of appearance and of speech was
      more frequently reported by the surgical group. Sixty-seven percent of the
      surgically treated patients reported pain relief, as opposed to only 29% of the
      nonsurgical group. CONCLUSION: Composite QOL-score sensitivity may be compromised
      by inverse changes in individual QOL domains. Treatment-specific QOL domains may
      be more sensitive measures of outcome.

PMID- 9278755
TI  - Paranasal sinus fungus balls.
AB  - BACKGROUND: Paranasal sinus fungus balls (mycetomas) are a form of fungal sinus
      infection distinct from allergic fungal sinusitis, fulminant invasive fungal
      disease, and paranasal aspergillus granulomas. METHODS: The Mayo Clinic surgical
      pathology files of inflammatory sinus specimens from 1984 to 1994 were examined.
      Twenty-nine paranasal sinus fungus balls were identified. Cases of allergic
      fungal sinus and invasive fungal disease were excluded. RESULTS: The fungus ball
      occurred in 11 men and 18 women, with an age range of 28 to 86 years, mean 64
      years. Sinuses involved included maxillary (20 cases), sphenoid (10 cases),
      ethmoid (9 cases), and frontal (6 cases). In 12 patients, multiple sinuses were
      involved in a variety of combinations. By culture the most common pathogens were
      Aspergillus fumigatus and Aspergillus flavus. Treatment was by a variety of
      surgical procedures. Follow-up in 28 patients showed two recurrences and three
      deaths due to intracerebral bleed as a complication of surgery. These deaths
      occurred in patients with sphenoid sinus fungus balls. CONCLUSIONS: Paranasal
      sinus fungus balls occurs in an elderly population and have a female
      predominance. They have a low morbidity and recurrence rate. Death can occur in
      sphenoid sinus lesions as a complication of surgery.

PMID- 9278756
TI  - Voice restoration after laryngectomy: experience with the Blom-Singer extended
      wear indwelling tracheoesophageal voice prosthesis.
AB  - BACKGROUND: The Blom-Singer tracheoesophageal voice prosthesis has undergone
      continuous design modifications during the last 18 years to make it more
      effective, anatomically compatible, and easier to use. This evolution continues
      with the recent introduction of an indwelling-style voice prosthesis intended for
      use by individuals who are unable or disinclined to use a self-removable-style
      voice prosthesis. The a priori self-lifespan goal of the indwelling prosthesis
      was 180 days. METHODS: The present investigation describes the experience of 81
      consecutive participants who used a total of 206 indwelling voice prosthesis.
      Selection criteria included total laryngectomy and either primary (n = 35) or
      secondary (n = 46) tracheoesophageal puncture. All participants had external-beam
      radiotherapy either pre- or postlaryngectomy. Specifically, lifespan of the
      prosthesis, the effects and clinical management of fungal colonization, and
      participant satisfaction with this style prosthesis were studied. RESULTS: A
      prosthesis use rate of 90% was observed. Group 1 prostheses (without fungal
      colonization and without Nystatin therapy) exhibited a lifespan significantly
      longer than did group 2 prostheses (with fungal colonization and prior to
      Nystatin therapy) (sample mean [mean] = 185.6 days versus 80.6 days; p < .05).
      Group 3 prostheses (following Nystatin therapy) also exhibited a lifespan
      significantly longer than that of group 2 prostheses (mean = 156.1 days versus
      80.6 days; p < .05). Lifespans of group 1 and group 3 prostheses were not
      significantly different (p < .05). CONCLUSIONS: The extended-wear, indwelling
      voice prosthesis achieved its a priori lifespan goal of 180 days (6 months) with
      almost uniform patient preference and without risk of increased complications.
      When fungal colonization was present. Nystatin therapy significantly prolonged
      prosthesis lifespan.

PMID- 9278758
TI  - Development of distant metastasis after treatment of advanced-stage head and neck
      cancer.
AB  - BACKGROUND: The recognition of risk factors for the development of distant
      metastasis is necessary for identifying high-risk patients who may benefit from
      systemic therapy. Previous investigations studying possible risk factors have
      been heterogeneous, with patients having varied forms of therapy. This study is
      designed to evaluate the clinical and histologic risk factors for the development
      of distant metastasis (DM) in patients with only advanced-stage head and neck
      squamous cell carcinoma after surgery and radiotherapy. METHODS: Retrospective
      analysis of a cohort of potentials with-surgically treated stage III and IV
      squamous cell carcinoma of the hypopharynx, tongue, and supraglottic larynx
      between 1988-1992. The cohort consisted of 130 patients of which 30 patients
      developed DM as the initial site of failure. All patients underwent surgical
      resection of the primary. Neck dissection was performed in 26 of 30 (87%0
      patients who developed distant metastasis. Almost all patients received radiation
      therapy. Patients who initially developed DM (DM group) were compared with
      patients who did not initially develop DM (no DM group) with respect to certain
      clinical and histo-pathological factors. RESULTS: The majority of patients in the
      DM group had advanced T stage and clinically palpable cervical lymph nodes (73%
      and 93% respectively). In the no DM group, most patients had advanced T stage
      (85%) but 42% of the patients had stage NO necks (p < .05). Eighty-eight percent
      of patients in the DM group and 60% of patients in the no DM group had
      histological evidence of extracapsular spread of tumor from cervical lymph nodes
      (p < .05). Three or more positive lymph nodes were found in 69% of patients who
      developed DM and in only 35% of patients in the no DM group (p < .05). Age,
      gender, primary site, history of radiation therapy, perineural invasion and tumor
      grade were not associated with a higher risk for DM (p > .05). CONCLUSION:
      Patients wit clinically palpable neck disease (N1-3), histological evidence of
      metastatic nodal disease, extracapsular spread, and three or more positive lymph
      nodes are at greater risk of developing failure at distant sites. This subset of
      patients should have an extensive evaluation for distant metastatic disease and
      should be considered for systemic therapy.

PMID- 9278757
TI  - Combined surgery and postoperative radiotherapy for carcinoma of the base of
      radiotherapy for carcinoma of the base of tongue: analysis of treatment outcome
      and prognostic value of margin status.
AB  - BACKGROUND: Choice of treatment for base of tongue carcinoma is controversial,
      with options including surgery alone, radiotherapy alone, or multimodality
      treatment. Given the highly aggressive nature of these tumors, it has been our
      institutional policy to manage this disease with combined partial glossectomy
      (with attempt to avoid laryngectomy if possible) with planned postoperative
      radiotherapy (RT). We reported on our institutional experience with this
      approach. METHODS: A retrospective review of the charts of 17 patients with
      primary base of tongue squamous cell carcinoma treated with surgery and
      postoperative RT was performed. Patients treated with chemotherapy as part of
      their management were excluded. All patients underwent partial, hemi-, or
      subtotal glossectomy; 15/17 patients underwent ipsilateral radical or modified
      radical neck dissection. All patients received comprehensive postoperative RT
      (median dose 6000 cGy; range 5040-6920 cGy). Stage distribution was as follows:
      stage I, 2; stage II, 3; stage III, 2; stage IV, 10. Positive margins for
      invasive carcinoma were found in 9/17 patients. Median follow-up of surviving
      patients is 46 months; median follow-up for all patients is 31 months. RESULTS:
      For the entire group of patients, the actuarial 3-year local-regional control
      rate was 68%. The actuarial 3-year overall survival rate was 46%. The local
      regional control rate was 83% for patients with stage I-III disease versus 50%
      for stage IV disease. There were no local failures among eight patients with
      negative margins (local control 100%) compared with an actuarial local control
      rate of 36% among patients with positive margins (p = .03). Survival, disease
      specific survival, and locoregional control were also highly correlated with
      margin status (p = .003). Late major complications included 5/17 patients
      requiring permanent G-tubes and/or tracheostomy to prevent aspiration.
      CONCLUSIONS: Surgery plus postoperative RT is an intensive treatment for
      carcinoma of the base of tongue which offers high locoregional control in
      patients in whom negative margins are achieved. Positive margins indicate a high
      risk of locoregional and systemic failure, and these patients should be
      considered for innovative clinical trials after surgery.

PMID- 9278759
TI  - Combined-modality therapy for squamous carcinoma of the buccal mucosa: treatment
      results and prognostic factors.
AB  - BACKGROUND: Reports on locoregional control and survival of squamous cell
      carcinoma of buccal mucosa are scarce in literature. In this study, a single
      institutions's experience of combined surgery and postoperative radiotherapy (RT)
      for buccal mucosal malignancy with favorable results was analyzed and presented.
      The prognostic factors on locoregional control were also discussed. METHODS: From
      January 1988 to July 1994, 57 patients with squamous cell carcinoma of buccal
      mucosa treated by surgery and RT were reviewed. The distributions according to
      American Joint Committee on Cancer (AJCC) staging were: stage II, 6; stage III,
      21; and stage IV, 30 patients. Total dose of RT at the buccal area ranged from 45
      Gy to 68.4 Gy, median 61.2 Gy. Tumor-related factors (AJCC stage, T stage,
      histologic grading, pathologic tumor invasion to skin of cheek, adjacent bony
      structures, and regional lymph nodes) and treatment-related factors (surgical
      margin, radiation dose, and the time interval between operation and RT) were
      analyzed to determine their influence on locoregional control. RESULTS: Three
      year actuarial locoregional control rate, overall survival rate, and disease
      specific survival rates were 64%, 55%, and 62%, respectively. Ten of these 22
      patients (45%) with recurrent tumors were reoperated, but only 2 patients were
      successfully salvaged. Positive surgical margin and tumor invasion to skin of
      cheek were significantly poor prognostic factors on locoregional control by
      univariate analysis. In multivariate analysis, tumor invasion to skin of cheek
      was the only prognostic factor (p = .0014). CONCLUSIONS: Locoregional failure was
      the major cause of death for squamous buccal mucosa cancers managed with surgery
      and RT. Few recurrences could be detected early and successfully salvaged. Skin
      of cheek involvement is an important prognostic factor for buccal mucosa cancers.

PMID- 9278760
TI  - Head and neck osteosarcoma at the University of Washington.
AB  - BACKGROUND: Head and neck osteosarcoma is a comparatively rare and aggressive
      malignancy. Our goal was to examine the experience of head and neck osteosarcoma
      patients seen over a 15-year period at the University of Washington Medical
      Center and compare this with the published experience of other centers in terms
      of demographics, histology, treatment, and survival rate. METHODS: We reviewed
      surgical pathology slides and clinical treatment records of 13 patients who were
      treated at the University of Washington Medical Center between 1981 and 1996. A
      total of 17 cases from 13 patients (13 primary tumors and 4 recurrences) were
      studied. RESULTS: There was a slight male predominance, with a male:female ratio
      of 1.6:1, and median age at diagnosis of 40.9 years (range 22 to 75 years), both
      slightly higher than has been generally reported. Three of 13 patients had
      recognized risk factors for the development of osteosarcoma: 2 with a history of
      prior radiotherapy and 1 with Paget's disease. All surgical pathology specimens
      were examined independently by two pathologists for histologic grading and
      typing. At initial presentation, 9/13 (69%) cases had conventional (osteoblastic)
      histology; 2/13 (15%) were fibroblastic, 1 chondroblastic (8%) and 1 parosteal
      (8%). Eight of 13 (62%) cases were high grade at initial presentation. Four of 13
      (30%) of the primary tumors were low grade 2, of which did not recur over a
      median follow-up period of 24 months. The other 2 low-grade tumors later recurred
      locally, as high-grade osteosarcomas, after disease-free intervals of 1 year and
      14 years, respectively. One patient had an intermediate-grade tumor which has not
      recurred as of last follow-up. Combined-modality treatment, including surgery
      with or without radiotherapy and/or chemotherapy, was given depending on the
      histologic grade, surgical margins, and recurrence. Some patients with low-grade
      tumors had surgery only. There were 5 local recurrences, 1 of these following a
      disease-free interval of 14 years. One patient had 3 separate recurrences at the
      same site. Ten of 13 (77%) are alive and disease-free. Of the 3 deaths, 1 was
      related to radiation-induced brain necrosis, without evidence of recurrent tumor.
      The project 5-year overall survival in this series is 72%, with a mean follow-up
      of 58 months (median, 36 months). Of those receiving neoadjuvant chemotherapy,
      6/7 have survived to the present. CONCLUSION: Given the limitations of a small
      patient population, our data suggest that neoadjuvant chemotherapy may provide
      benefit in terms of survival. Longer follow-up will be necessary to support this
      conclusion. Our data also show that our population has a higher-than-average age
      of onset, low presence of risk factors, and better survival rate in comparison
      with the published series from other institutions.

PMID- 9278761
TI  - Functional outcome in soft palate reconstruction using a radial forearm free flap
      in conjunction with a superiorly based pharyngeal flap.
AB  - BACKGROUND: Speech and swallowing problems due to velopharyngeal incompetence may
      follow soft palate resection and reconstruction. Over the past 3 years, we have
      developed the use of a superiorly based pharyngeal flap in conjunction with a
      radial forearm flap for soft palate reconstruction. METHODS: This paper describes
      the technique in detail and compares the functional results in a study with
      patients undergoing soft palate resection for squamous cell carcinoma treated
      with or without a pharyngeal flap as an adjunct to a radial forearm free flap for
      soft palate reconstruction. Seven patients had one quarter or one half soft
      palate defects reconstructed with a radial forearm flap alone. Of the 11 patients
      undergoing three quarter or total soft palate resections, all were reconstructed
      with a radial forearm flap, but 5 were treated with an additional superiorly
      based pharyngeal flap. The functional outcome for all the patients was analyzed
      and compared. RESULTS: Our results show that the addition of the superiorly based
      pharyngeal to the radical forearm flap in soft palate reconstruction results in
      improved speech and swallowing. We recommend the use of the additional flap in
      resections in which more than one quarter of the soft palate is included.

PMID- 9278762
TI  - Super-supraglottic swallow in irradiated head and neck cancer patients.
AB  - BACKGROUND: After radiotherapy to the head and neck, many patients experience
      swallowing difficulties. Preliminary work indicates that these patients benefit
      from the super-supraglottic swallow maneuver. METHODS: Lateral videofluoroscopic
      studies examined oropharyngeal swallowing in 9 patients who suffered from
      dysphagia after radiation to the head and neck. Each patient completed two
      swallows each of 1 mL or 3 mL liquid barium without a voluntary swallow maneuver
      and with the super-supraglottic swallow designed to close the entrance to the
      airway early. The videotape of each swallow was digitized and the location of
      pharyngeal structures marked throughout the swallow. Movement over time plots
      were generated to measure changes in structural movement resulting from the
      maneuver. RESULTS: The super-supraglottic swallow resulted in changes in airway
      entrance closure and hyolaryngeal movement. One patient who aspirated without the
      maneuver stopped aspirating with the maneuver. Two others had aspiration reduced
      to a trace with the maneuver. Fewer swallowing disorders were observed with the
      maneuver. CONCLUSION: The super-supraglottic swallow results in improved
      biomechanics of swallow in irradiated head and neck cancer patients.

PMID- 9278763
TI  - Reconstruction of partial laryngopharyngectomy defects.
AB  - As our contributors to this section have pointed out, there are at present two
      main methods of reconstructing defects of the pharynx and cervical esophagus:
      free jejunal transfer (FJT) and tubed radial forearm flap. The advantage of the
      FJT is that it is a tube, thus limiting the enteric suture lines to proximal and
      distal. The radial forearm flap requires not only the proximal and distal suture
      lines but a long longitudinal suture line to create the tube. This increase the
      possibility for fistula formation. The controversy surrounding this case concerns
      what to do with a remaining mucosal strip after a subtotal laryngectomy.
      Traditional reconstructive principles would dictate that normal tissue should not
      be sacrificed, but some would argue that the remaining mucosa should be
      sacrificed to allow for use of a FJT. The other alternative would be use of a
      radical forearm skin flap tubed to 270 degrees. At the University of Texas M. D.
      Anderson Cancer Center, we preferentially use the FJT for almost all defects and
      would probably have sacrificed the remaining mucosal strip in this particular
      case. We have used skin flaps to patch pharyngeal defects and prevent stricture
      in a number of cases. This is usually done however when the remaining pharyngeal
      mucosa approaches 50% or greater. Although we do not routinely use the tubed
      radial forearm flap because of the increased rate of fistula formation, there are
      some definite indications for its use. The first important indication is in
      patients in whom speech rehabilitation is desired or indicated. The skin flap
      provides a stiffer resonating chamber for the speech production and does not have
      the peristalsis or the mucus production associated with the jejunal flap. Another
      indication for use of radial forearm flap would be when there is a
      contraindication to celiotomy, ie, patients with hepatic cirrhosis and associated
      ascites or other abdominal conditions precluding abdominal exploration. In this
      situation, avoiding an intra-abdominal procedure would limit operative morbidity.
      In conclusion, one should use whichever procedure obtains a healed wound and re
      establishes continuity of the upper gastrointestinal tract. In our hands,
      retention of the remaining mucosal segment would not be critical in this
      particular case and in fact would present a hindrance to use of the FJT.

PMID- 9278764
TI  - Calcific tendinitis of the longus colli muscle.
AB  - BACKGROUND: To the best of our knowledge, only one patient with calcium
      hydroxyapatite deposition disease (CHADD) of the longus colli muscle has been
      reported in the otolaryngology literature. METHODS: Clinical findings and results
      of imaging studies in such a patient are reported. RESULTS: Two particular
      imaging findings of this disorder are discussed. First, disappearance of
      calcifications over the short time frame of a week, accompanied by the resolution
      of clinical symptoms. Second, the presence of an extensive region of high signal
      intensity extending from the skull base to the lower border of C5, on T2-weighted
      spin-echo magnetic resonance (MR) images. CONCLUSIONS: Knowledge of the
      characteristic clinical spectrum and imaging features of this disorder are
      crucial for a correct diagnosis of this uncommon cause of odynophagia and
      dysphagia.

PMID- 9278765
TI  - Synovial sarcoma of the head and neck: chromosomal translation (X;18) as a
      diagnostic aid.
AB  - BACKGROUND: Synovial sarcoma, a rare tumor in the head and neck, has been
      historically diagnosed by its characteristic biphasic histologic pattern.
      Monophasic variants exist which can be difficult to diagnose. METHODS: Two cases
      of synovial sarcoma of the head and neck are presented. Both cases, cytogenetic
      analysis was performed using standard protocols. RESULTS: Both tumors
      demonstrated a chromosomal translocation, t(X;18)(p11.2;q11.2), which either made
      or confirmed the diagnosis. CONCLUSIONS: Synovial sarcoma contains a
      characteristic chromosomal translocation which is a useful diagnostic tool,
      especially when histologic studies are equivocal.

PMID- 9278766
TI  - Analysis of thermal parameters obtained during phase III trials of hyperthermia
      as an adjunct to radiotherapy in the treatment of breast carcinoma.
AB  - An analysis of 351 HT treatment sessions administered to 101 patients receiving
      radiotherapy and hyperthermia (RT + HT) who were entered into Phase III
      concurrent randomized trials for recurrent (BrR) and intact (BrI) breast tumours
      is presented. A complete response (CR) was recorded in 50 of 84 (59.5%) fields in
      the case of recurrent breast patients and in 10 of 17 (59%) fields in the case of
      the intact breast patients. In comparison, 15 of 60 (25%) patients entered into
      BrR who received RT alone and 8 of 12 (66.7%) patients receiving RT alone entered
      into BrI trial achieved CR. A set of thermal parameters is defined and evaluated
      on a treatment by treatment basis. Patient and tumour characteristics influential
      on CR are identified and thermal parameters which have additional prognostic
      value are investigated. Multivariate logistic analysis of the non-thermal data
      showed that maximum depth of tumour, presence or history of disease outside the
      treated area and RT regimen were most influential on CR. Tumour volume (cm3) (OR
      = 0.996, 95% CI = 0.993-1.004, p = 0.08) was not a strong prognostic covariate;
      tumour area and linear dimensions were even less significant (p = 0.41). The
      cumulative minimum thermal isoeffect dose (equivalent minutes at 43 degrees C)
      accrued over the 1st, 1st and 2nd, and 1st, 2nd and 3rd treatment sessions was
      the only thermal parameter to exhibit an association with CR consistently, Other
      thermal parameters found to contribute to the predictive models were MINTIME > 42
      degrees C calculated for the first treatment session and %sensors > 43 degrees C
      (peak) calculated for the 2nd treatment session.

PMID- 9278767
TI  - The influence of vasculature on temperature distributions in MECS interstitial
      hyperthermia: importance of longitudinal control.
AB  - The quality of temperature distributions that can be generated with the Multi
      Electrode Current Source (MECS) interstitial hyperthermia (IHT) system, which
      allows 3D control of the temperature distribution, has been investigated. For the
      investigations, computer models of idealised anatomies containing discrete
      vessels, were used. A 7-catheter hexagonal implant geometry with a nearest
      neighbour distance of 15 mm was used. In each interstitial catheter with a
      diameter of 2.1 mm a number of 1 up to 4 electrodes were placed along an 'active
      section' with a length of 50 mm. The electrode segments had lengths of 50, 20, 12
      and 9 mm respectively. Both single vessel and vessel network situations were
      analysed. This study shows that even in situations with discrete vasculature and
      perfusion heterogeneity it remains possible to obtain satisfactory temperature
      distributions with the MECS IHT system. Due to its 3D spatial control the
      temperature homogeneity in the implant can be made quite satisfactory.

PMID- 9278768
TI  - Anti-tumour effects of localized hyperthermia on an experimental bone tumour
      using an intramedullary nail.
AB  - A new localized hyperthermia system for an experimental bone tumour in the rabbit
      tibia was developed. This system was composed of an induction coil, generator and
      a Kirschner wire, which was inserted into the medullary canal of the tibia as a
      heat-generating ferromagnetic implant. The metastatic bone tumour model was
      created by implantation of VX2 carcinoma in the medullary canal of the tibia
      diaphysis. The days after VX2 implantation, hyperthermia was induced for 50 min.
      Three weeks after the treatment, rabbits were sacrificed for histological and
      radiological evaluation. According to the semi-quantitative scoring system, anti
      tumour effects of the single dose of hyperthermia was noted radiologically (p <
      0.01) and histologically (p < 0.05) where the temperature was at a sufficient
      level to cause hyperthermia (> 42.5 degrees C). This new heating method, which is
      relatively simple and clinically applicable, appears to be promising for the
      treatment of metastatic tumours of the long bone.

PMID- 9278769
TI  - Alteration in the hypoxic fraction of quiescent cell populations by hyperthermia
      at mild temperatures.
AB  - We investigated oxygenation of quiescent (Q) tumour cells in vivo by mild heat
      treatment. C3H/He mice bearing SCC VII tumours received BrdU continuously for 5
      days via implanted mini-osmotic pumps, to label all proliferating (P) cells. The
      tumours were then irradiated after treatment, and were excised, minced and
      trypsinized. The tumour cell suspension thus obtained were incubated with
      cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in
      cells without BrdU labelling was determined using immunofluorescence staining for
      BrdU. This MN frequency was then used to calculate the surviving fraction of
      unlabelled cells from the regression line for the relationship between the MN
      frequency and the surviving fraction of total (P + Q) tumour cells. Thus, a cell
      survival curve could be determined for the cells not labelled with BrdU, which
      can be regarded as the Q cells in a tumour for all practical purposes. The MN
      frequency in total tumour cell population was determined from the irradiated
      tumours that were not pretreated with BrdU. Assays performed immediately after
      irradiation of both normally aerated and hypoxic tumours showed that Q cells
      contained higher hypoxic fractions than the total tumour cell population. Mild
      heat treatment (40.0 degrees C, 60 min) before irradiation decreased the hypoxic
      fraction, even when is was combined with nicotinamide administration. In
      contrast, mild heating did not decrease the hypoxic fraction when the mice were
      placed in a circulating carbogen (95% O2/5% CO2) chamber. Therefore, mild heat
      treatment was thought to preferentially oxygenate the chronically hypoxic
      fraction.

PMID- 9278770
TI  - The response on glucoregulatory hormones of in vivo whole body hyperthermia.
AB  - This study was designed to examine the effects of in vivo hyperthermia on the
      circulating concentrations of a number of glucoregulatory hormones potentially
      involved in immunomodulation. Eight healthy male volunteers were immersed for 2 h
      in a hot water bath (water temperature 39.5 degrees C) (WI) during which period
      their rectal temperature rose to 39.5 degrees C. In a control study the subjects
      were immersed in thermoneutral water (water temperature 34.5 degrees C). Blood
      samples were collected before, at body temperature 38 degrees C (42.5 (30-52),
      median and range), minutes of hot WI, 39 degrees C (72.5 (58-97) minutes of hot
      WI), and 39.5 degrees C (at the end of 2 h of hot WI), as well as 1 and 2 h after
      cessation of 2 h of hot WI. In the control experiment blood samples were
      collected at identical time points. The growth hormone concentrations were
      elevated already at 38 degrees C to 24.2 (3.9-55.0) mU/l and peaked at 39 degrees
      C to 48.4 (20.8-81.5) mU/l compared to 0.3 (0.3-9.0) mU/l at baseline; at 39.5
      degrees C the concentration declined to 31.6 (13.0-48.0) mU/l and further to 7.4
      (0.8-17.3) mU/l 1 h after ending hot WI. The beta-endorphin levels were augmented
      at 39 degrees C and 39.5 degrees, to 8.0 (3.4-27.8) pmol/l and 8.1 (3.1-44.6)
      pmol/l, respectively, from 2.2 (0.7-5.6) pmol/l baseline. Glucagon levels raised
      from 23.0 (12.0-32.0) pmol/l to 32.0 (24.0-52.0) pmol/l at 39 degrees C, and to
      38.5 (26.0-57.0) pmol/l at 39.0 degrees C. Insulin levels remained unchanged.
      Plasma glucose increased from 4.75 (4.2-7.6) mmol/l to 5.20 (4.6-5.6) mmol/l
      alone after 90 min of WI (temperature 39-39.5 degrees C). It is concluded that in
      vivo whole body WI hyperthermia increases the circulating levels of several
      essential glucoregulatory hormones.

PMID- 9278771
TI  - Ferromagnetic hyperthermia: functional and histopathologic effects on normal
      rabbit ocular tissue.
AB  - Ferromagnetic (FM) hyperthermia has previously been evaluated in a rabbit tumour
      model of ocular melanoma. To study the effect of focal heating in normal rabbit
      eyes, FM seeds were implanted into a 14-mm episcleral plaque an heated to
      operating temperatures of 48 or 58 degrees C. Thermal induction was performed by
      placing rabbits in a uniform, oscillating (11 kHz) magnetic field operating at
      1200 W and as H-field strength of 265 A/m. Eyes were heated for 60 min with
      continuous scleral temperature monitoring. Hyperthermic effects were monitored by
      direct opthalmic examination, fundus photography, serial electroretinography and
      histopathology. Intraocular temperatures were mapped with direct fiberoptic
      thermometry. All treatment effects were confined to the area covered by the
      episcleral plaque. Direct ophthalmoscopic examination revealed early retinal
      whitening during heat induction followed by localized exudative retinal
      detachments, limited to the area of the retinal surface overlying the plaque,
      that resolved spontaneously. Serial electroretinography was virtually
      indistinguishable between the 48 and 54 degrees C temperature groups. We noted a
      minimal alteration in a- and b-wave amplitudes with no changes in implicit times.
      Histopathology at 3 weeks post-treatment documented chorioretinal scarring
      overlying the thermal plaque treatment zone. No evidence of heamorrhage
      infection, cataract or scleral thinning was noted. This study documents the
      apparent focal containment of thermal effects with FM heating utilizing operating
      temperatures ad high as 54 degrees C for 60 min, and discloses no evidence of
      diffuse ocular toxicity.

PMID- 9278772
TI  - Comment on response to paper by d'Oleire et al.

PMID- 9278773
TI  - Vasoconstriction of rat renal interlobar arteries by noradrenaline and
      neuropeptide Y.
AB  - 1. We have studied the contractile effects of noradrenaline and neuropeptide Y
      given alone and in combination on isolated rat renal interlobar arteries. 2.
      Noradrenaline contracted proximal and distal intrarenal microvessels in a
      concentration dependent manner, with similar potency (EC50 approximately equal to
      550 nM), but maximal effects were greater in the proximal than in the distal
      vessel segments (approximately equal to 10 and 6 nM, respectively). 3. The
      noradrenaline-induced contraction was inhibited by low prazosin concentrations (3
      10 nM) but not by 1 microM yohimbine indicating involvement of alpha(1)-but not
      alpha(2)-adrenoceptors. The alpha(1)A-adrenoceptor-selective antagonist, 5
      methylurapidil and tamsulosin, had high potency (apparent affinities of
      approximately equal to 8 nM and 57 pM, respectively) while the alpha(1)D
      adrenoceptor-selective antagonist, BMY 7378, had only low potency (apparent
      affinity approximately equal to 300 nM). The alpha(1)B-adrenoceptor-alkylating
      agent, chloroethylclonidine (10 microM for 30 min at 37 degrees C), had no
      inhibitory effects. The Ca2+ entry blocker, nitrendipine (300 nM), reduced the
      potency and maximal effects of noradrenaline. 4. Neuropeptide Y (1-100 nM) also
      contracted interlobar arteries in a concentration dependent manner, with greater
      effects in the proximal than in the distal segments, but maximal effects were
      only small in either segment (< 2 mN). In addition, neuropeptide Y also
      potentiated the response to noradrenaline, i.e. lowered its EC50 but this
      enhancement was also small. 5. We conclude that noradrenaline contracts rat
      interlobar arteries by an alpha(1)A-adrenoceptor; its co-transmitter,
      neuropeptide Y, affects the response only marginally in this vascular bed.

PMID- 9278774
TI  - Age-related changes in the reactivity of postsynaptic adrenoceptors in the rat
      vas deferens: differences between the epididymal and prostatic portion.
AB  - 1. Age-related changes in the reactivity of postsynaptic alpha-adrenoceptors of
      isolated portions (epididymal and prostatic) and in whole vas deferens have been
      studied using 4, 12 and 20 month-old rats. 2. The pD2 values for adrenaline
      induced contractions were reduced in the epididymal portion and whole vas
      deferens of middle-aged and old animals, but not in the prostatic portion. No age
      related change to phenylephrine or clonidine sensitivity was observed. 3. pA2
      values of prazosin and yohimbine were not changed by aging in any preparation.
      Phentolamine pA2 values were reduced in the epididymal portion and in the whole
      vas deferens when adrenaline, but not when phenylephrine concentration-response
      curves were displaced by the antagonist. The mean pA2 value of yohimbine (6.78)
      indicates that this antagonist blocks alpha(1)-adrenoceptors in the rat vas
      deferens. 4. The data presented here suggest that age-related decreases in the
      sensitivity to adrenaline and phentolamine (when measured by displacing
      adrenaline concentration-effect curves) in the whole vas deferens are probably
      due to a variation in the proportion of alpha(1)-adrenoceptor subtypes in the
      epididymal portion of the rat vas deferens.

PMID- 9278776
TI  - Effects of esmolol on 35 GHz microwave-induced lethal heat stress.
AB  - 1. The purpose of this study was to examine effects of the beta(1)-adrenoreceptor
      antagonist esmolol (infused at 2 or 4 mg kg-1 body wt min-1) on heart rate, blood
      pressure, respiratory rate, localized body temperature changes, survival times,
      and lethal body temperatures that occur during the exposure of anaesthetized rats
      to 35 GHz microwaves. 2. Forty Sprague-Dawley rats, anaesthetized with ketamine,
      were exposed to 35 GHz microwaves at a level that resulted in heating and death.
      During irradiation, a continuous increase in heart rate and a biphasic response
      in blood pressure (initial increase followed by a decrease) were observed in all
      groups of animals. 3. Esmolol caused a significant dose-dependent decrease in
      blood pressure, relative to saline-treated animals, but only a small attenuation
      of the heat-induced rise in heart rate. In experiments in which esmolol was
      infused and microwave exposure was continued until death, drug-treated animals
      survived for significantly shorter periods and died at significantly lower body
      temperatures. The change in survival may have been related to the lower blood
      pressure due to esmolol treatment.

PMID- 9278775
TI  - Intracerebroventricular choline reverses hypotension induced by acute chemical
      sympathectomy.
AB  - 1. The effect of centrally administered choline on blood pressure was
      investigated in rats made hypotensive by chemical sympathectomy. Chemical
      sympathectomy was produced by intravenous (i.v.) injection of 50 mg kg-1 of 6
      hydroxydopamine (6-OHDA). Intracerebroventricular (i.c.v.) administration of
      choline (50-150 micrograms) 2 h after 6-OHDA treatment increased blood pressure
      and reversed the hypotension in a dose-dependent manner without affecting the
      heart rate. The pressor response was associated with an increase in plasma
      vasopressin levels. 2. Pretreatment of rats with the nicotinic receptor
      antagonist, mecamylamine (50 micrograms, i.c.v.), but not the muscarinic receptor
      antagonist atropine (10 micrograms, i.c.v.), blocked both the pressor and
      vasopressin responses to choline (150 micrograms). Pretreatment of rats with
      hemicholinium-3 (HC-3), a high affinity choline uptake inhibitor, greatly
      attenuated the pressor response to i.c.v. choline (150 micrograms). 3. The
      vasopressin V1 receptor antagonist, beta-mercapto-beta,beta
      cyclopentamethylenepropionyl-O-Me-Try,Arg) - vasopressin (10 micrograms kg-1;
      i.v.) given 5 min after i.c.v. choline, decreased the blood pressure but failed
      to return it to the pre-choline levels. Prazosine (0.5 mg kg-1; i.p.), an
      antagonist of alpha-adrenoceptors, also decreased blood pressure. Administration
      of both antagonists together eliminated the pressor response to choline, and the
      blood pressure was reduced further to below the pre-choline levels. 4. It is
      concluded that i.c.v. choline can increase blood pressure in rats made
      hypotensive by acute chemical sympathectomy through the activation of central
      nicotinic receptors by presynaptic mechanisms. An elevation in plasma levels of
      both vasopressin and catecholamines (possibly released from the adrenal medulla)
      is involved in the pressor response to choline.

PMID- 9278777
TI  - Beta(3)-adrenoceptors mediate smooth muscle relaxation in the rat lower
      oesophageal sphincter.
AB  - 1. The role of beta(3)-adrenoceptors in isoprenaline-induced relaxation of
      carbachol-precontracted ring segments of the rat lower oesophageal sphincter
      (LOS) was examined. 2. Isoprenaline (10(-8)M-10(-5)M) relaxed ring segments of
      the LOS in a concentration-dependent manner. Propranolol (10(-7)M) had very
      little antagonist effect on isoprenaline-induced relaxation. 3. Dobutamine (10(
      7)M-10(-4)M), salbutamol (10(-7)-10(-4)M) and BRL 37344 (10(-8)-10(-5)M) also
      relaxed carbachol-contracted ring segments of the LOS in a concentration
      dependent manner. The relaxant responses to these agonists were similarly not
      antagonized by propranolol (10(-7)M). 4. Cyanopindolol (10(-6)M), produced a
      parallel rightward displacement of isoprenaline, dobutamine, salbutamol and BRL
      37344 concentration-response curves with similar potencies. The pKB values range
      from 7.3 +/- 0.1 to 7.7 +/- 0.2. 5. The relaxant effect of isoprenaline in the
      rat LOS was not inhibited by NG-nitro-L-arginine (L-NOARG; 3 x 10(-5)M),
      glibenclamide (10(-5)M) or tetraethylammonium (1 mM). 6. It was concluded that
      beta(3)-adrenoceptors mediate isoprenaline-induced relaxation in rat lower
      oesophageal sphincter and that activation of these receptors was not linked to
      either ATPase-, Ca(2+)-dependent K+ channels or to NO release.

PMID- 9278778
TI  - The effects of bromoacetylalprenololmenthane on the responses to isoprenaline of
      the left ventricle from normo-, prehyper- and hypertensive rats.
AB  - 1. We have studied the effects of bromoacetylalprenololmenthane (BAAM), a very
      slowly reversible beta-adrenoceptor antagonist, on the responses of the left
      ventricle of 5 and 22 week old Wistar Kyoto (WKY) rats and spontaneously
      hypertensive rats (SHRs) to isoprenaline. At 5 weeks the SHRs were
      prehypertensive and at 22 weeks they had hypertension-induced hypertrophy of the
      left ventricle. 2. The mean potency of isoprenaline on the left ventricle from 5
      week old WKY was similar to that obtained on left ventricle with BAAM at 10(-6) M
      for 30 min, there was a parallel rightward shift of the isoprenaline
      concentration-response curves. Treatment with a higher concentration of BAAM (10(
      5)M) caused non-parallel rightward shifts of the concentration-response curves,
      with a depression of the isoprenaline maximum responses. These data were used to
      derive affinity (KA) values for isoprenaline. The mean isoprenaline KA value on
      the left ventricle from 5 week old WKY was 2.44 x 10(-6)M, and similar KA values
      were obtained on the left ventricles from 22 week old WKY and 5 and 22 week old
      SHRs. On all the left ventricles tested, isoprenaline produced a half maximal
      response by occupying less than 1%, and a near maximal response by occupying
      about 5% of the available beta(1)-adrenoceptors. 4. This study has shown that
      there are no differences in the cardiac responses to isoprenaline at beta(1)
      adrenoceptors, isoprenaline KA values or the beta(1)-adrenoceptor reserve for
      isoprenaline on the SHR left ventricle in prehypertension or in the early stages
      of hypertension-induced hypertrophy.

PMID- 9278779
TI  - Pharmacological characterization of adrenoceptors in horse corpus cavernosum
      penis.
AB  - 1. The presence and types of alpha and beta-adrenoceptors in the corpus
      cavernosum of the horse were studied in vitro by using selected ligands of
      adrenoceptors and isometric tension recording. 2. Noradrenaline and phenylephrine
      induced concentration-dependent contractions in corpus cavernosum preparations. B
      HT 920 had no effect. 3. Phentolamine and prazosin produced a shift to the right
      of the dose-response curve of noradrenaline, while the alpha(2)-antagonist,
      rauwolscine had no effect on the response to noradrenaline. Phenylephrine-evoked
      contractions of corporal strips were significantly inhibited by the alpha(1)
      adrenoceptor antagonist, prazosin. 4. Isoprenaline and salbutamol each relaxed
      precontracted corpus cavernosum preparations in a concentration-dependent manner;
      the isoprenaline effect was blocked by propranolol, practolol and butoxamine. The
      salbutamol effect was blocked by butoxamine. 5. These results suggest that
      presence of postjunctional alpha(1)-adrenoceptors in horse corpus cavernosum.
      There is also a heterogenous population of beta-adrenoceptors in this tissue,
      belonging to the beta(1) and beta(2) subtypes.

PMID- 9278780
TI  - Considering corneal and lenticular techniques of refractive surgery.

PMID- 9278781
TI  - Advantage of plate lenses.

PMID- 9278782
TI  - Strategies of postoperative care.

PMID- 9278783
TI  - Is it cataract or misalignment that affects corneal topography measurements?

PMID- 9278784
TI  - Incidence and treatment of wrinkled corneal flap following LASIK.

PMID- 9278785
TI  - General or topical anesthesia?

PMID- 9278786
TI  - Retrobulbar block revised.

PMID- 9278787
TI  - Demonstrating glare to the surgical patient.

PMID- 9278788
TI  - Consultation section. Treating hyperopia.

PMID- 9278789
TI  - Bimanual technique to manage subincisional cortical material.
AB  - The aspiration of subincisional cortical material using a standard
      irrigation/aspiration (I/A) handpiece can be a difficult maneuver in
      phacoemulsification. Access to the cortex is restricted and made more problematic
      by an incision carried into clear cornea and a continuous curvilinear
      capsulotomy. A bimanual technique for I/A has been developed that provides better
      access to subincisional cortex and improved chamber maintenance during
      aspiration.

PMID- 9278791
TI  - Powder-free gloves for ophthalmic surgery.
AB  - Powdered and powder-free gloves were compared during ophthalmic surgery. It was
      found that powder may reappear on well-rinsed gloves by the end of intraocular
      surgery and be implanted inadvertently into the eye or in the stromal interface
      during laser in situ keratomileusis. Powder-free gloves, therefore, make surgery
      significantly safer.

PMID- 9278790
TI  - Monoscleral fixated lens implantation in eyes with partial loss of capsular or
      zonular support.
AB  - A technique is described in which a posterior chamber intraocular lens (IOL) is
      implanted in eyes with partial loss of posterior capsule or zonular support. The
      IOL's inferior haptic is placed over the residual capsule and the superior haptic
      is fixated to the ciliary sulcus with a polypropylene suture. In 17 eyes that had
      surgery using this technique, mean postoperative visual acuity was 20/25;
      complications included irregular pupil, iris capture, pupil block, hyphema,
      localized peripheral anterior synechia, IOL tilt, suture exposure, and cystoid
      macular edema.

PMID- 9278792
TI  - Mesopic vision in myopia corrected by photorefractive keratectomy, soft contact
      lenses, and spectacles.
AB  - PURPOSE: To evaluate contrast vision and glare sensitivity under mesopic
      conditions in eyes having uncomplicated excimer laser photorefractive keratectomy
      (PRK) for myopia and in eyes corrected by disposable soft contact lenses, soft
      contact lenses, and spectacles. SETTING: Division of Experimental Ophthalmic
      Surgery, University of Tubingen, Germany. METHODS: The Mesoptometer II test was
      used to evaluate mesopic vision (glare sensitivity and contrast vision) in 28
      eyes of 14 patients wearing disposable soft contact lenses, 20 eyes of 10
      patients wearing soft contact lenses, 39 eyes of 20 patients wearing spectacles,
      30 eyes of 15 emmetropic patients, and 33 eyes of 22 patients after PRK with 5.0
      mm optical zone. Follow-up was between 15 and 60 months after PRK (mean 34.5
      months). RESULTS: The guidelines of the German Ophthalmologic Society state that
      patients must recognize Mesoptometer II contrast levels of 1:5 or better with and
      without glare to meet the minimum legal night-driving standards for private cars.
      All eyes with disposable soft contact lenses and soft contact lenses, all
      emmetropic eyes, and 38 eyes corrected by spectacles recognized contrast levels
      of 1:5 or better without glare. In contrast, 18 eyes in the PRK group were unable
      to recognize contrast level 1:5 without glare. With glare, 1 eye in the
      disposable soft contact lens group, 1 in the soft contact lens group, and 7 with
      spectacles were unable to recognize the 1:5 contrast level. All emmetropic eyes
      recognized contrast levels of 1:5 or better; 22 PRK eyes were unable to recognize
      contrast level 1:5 with glare. CONCLUSION: Myopic PRK may lead to long-term
      impairment of mesopic vision, while soft contact lens use does not seem to
      markedly influence mesopic vision in eyes with low to moderate myopia.

PMID- 9278793
TI  - Photovaporization rate and profile of an erbium-chromium:YAG laser in the
      fundamental mode.
AB  - PURPOSE: To evaluate the ablation characteristics of an experimental erbium:YAG
      (Er:YAG) laser and assess whether it delivers sufficient output for performing
      photorefractive keratectomy. SETTING: Department of Ophthalmology, Virchow
      Clinics, Humboldt University, Berlin, Germany. METHODS: An experimental Er:YAG
      laser, the erbium-chromium:YAG, running in fundamental mode was used to evaluate
      the energy profile. Measurements obtained using a joulemeter were compared to the
      ablation profiles of cadaver pig eyes. The pig eyes were treated with different
      fluences (mean 0.8 to 2.9 J/cm2) and, after histological preparation, were
      examined using light and scanning electron microscopy. RESULTS: Measurements with
      the joulemeter and in the cadaver pig eyes showed a Gaussian-curved profile of
      energy (ablation). In the current setting, the diameter of ablation was 3.5 mm.
      Histological examination showed a homogeneous profile of ablation with minor
      thermal damage. CONCLUSION: The Er:YAG laser running in the fundamental mode
      allows homogeneous ablation of corneal tissue. The Er:YAG laser is easier to
      handle technically than the excimer laser and has none of the potential risks of
      ultraviolet light.

PMID- 9278794
TI  - Five years results of photorefractive keratectomy for myopia.
AB  - PURPOSE: To evaluate the long-term stability, complications, and causative
      factors in eyes that had photorefractive keratectomy (PRK) for myopia. SETTING:
      Kangnam St. Mary's Hospital, Seoul, Korea. METHODS: This study evaluated the
      results of PRK in 201 myopic eyes with a consecutive 5 year follow-up.
      Preoperative myopia ranged from 2.25 to 12.50 diopters (D), with astigmatism of
      less than 1.50 D. The Excimer laser was set to a maximum correction of -6.50 D at
      a 5.0 mm diameter ablation zone. Patients with more than 7.00 D of myopia had
      double-pass PRK with two different ablation zone sizes (5.0 and 4.5 mm). The data
      were statistically analyzed using polynomial regression for evaluating long-term
      stability and myopic regression and Cox's proportional hazard model for
      evaluating causative factors. RESULTS: An uncorrected visual acuity better than
      20/25 was achieved in 62.4% of eyes. The main complication after PRK was myopic
      regression. Mean refractive error 5 years after PRK was -2.43 +/- 1.90 D. It was 
      1.49 +/- 0.60 D in moderately myopic eyes (less than 6.50 D) and -3.55 +/- 2.31 D
      in highly myopic eyes (over 7.00 D). According to our evaluation, the possible
      causative factors for myopic regression were pre-PRK refraction (P < .0001) and
      post-PRK corneal haze (P = .01); their relative risks were 3.33 and 1.93,
      respectively. Multivariate analysis eliminated the corneal haze factor.
      CONCLUSION: Myopic regression occurred as long as 5 years after PRK, with the
      most important factor for myopic regression being pre-PRK refraction.

PMID- 9278795
TI  - Excimer laser photorefractive keratectomy in pediatric patients.
AB  - PURPOSE: To evaluate the results of excimer laser photorefractive keratectomy
      (PRK) for myopia in pediatric eyes with amblyopia resulting from anisometropia.
      SETTING: Clinica de Ojos Dr. Nano, Buenos Aires, Argentina. METHODS: Five
      children with amblyopia resulting from anisometropia in whom conventional therapy
      was unsuccessful had PRK followed immediately by photoastigmatic refractive
      keratectomy. Mean patient age was 12.4 years, and follow-up was 12 months.
      RESULTS: Postoperatively, all eyes had reduced anisometropia and a significant
      improvement in uncorrected and corrected visual acuities. Sixty percent of
      patients had no haze 12 months after PRK, 20% had trace haze, and 20%, mild. No
      patient had decreased best spectacle-corrected visual acuity. CONCLUSION: The
      results of PRK for myopia were good in this small sample of children. Longer
      follow-up with more patients should be done.

PMID- 9278796
TI  - Effectiveness of topical diclofenac in relieving photophobia after pupil
      dilation.
AB  - PURPOSE: To test the effectiveness of topical diclofenac in relieving photophobia
      after pupil dilation. SETTING: Department of Ophthalmology, Newcastle General
      Hospital, Newcastle-upon-Tyne, United Kingdom. METHODS: Twenty healthy patients
      and volunteers from the outpatient ophthalmology clinic were enrolled in a
      prospective, double-blind, placebo-controlled comparison in which the patient's
      fellow eye served as a control. Photophobia after pupil dilation was tested
      subjectively using a visual analog scale and a neutralization scale at 30 minute
      intervals for 2 hours after instillation of topical diclofenac. RESULTS: Both
      tests show a statistically significant reduction in photophobia in the diclofenac
      treated eyes at each time interval (P < or = .05). This difference was also
      considered clinically relevant. CONCLUSION: Topical diclofenac given at the time
      of pupil dilation significantly reduced photophobia. The mechanism of action is
      unknown and requires further evaluation.

PMID- 9278797
TI  - Efficacy and safety of combined diclofenac 0.1% and gentamicin 0.3% eyedrops
      after phacoemulsification.
AB  - PURPOSE: To study the efficacy of combined diclofenac 0.1% and gentamicin 0.3%
      (Digen) eyedrops to treat postoperative inflammation and prevent ocular infection
      in eyes having phacoemulsification. SETTING: Department of Ophthalmology,
      University of Milan, San Paolo Hospital, Milan; Eye Clinic, University of Verona;
      and Department of Ophthalmology, University of Palermo, Italy. METHODS: This
      double-masked, randomized, clinical trial comprised 90 patients; 45 received
      Digen and 45, gentamicin 0.3% eyedrops. The main outcome measure of the study was
      the reduction in signs and symptoms of inflammation, graded on a four-point
      scale. Also assessed were the presence of bacteria in the conjunctival swab and
      the proportion of patients requiring additional medication. RESULTS: Digen was
      more effective in reducing postoperative inflammation than gentamicin alone (P <
      .01). No statistically significant between-group difference was found regarding
      antibacterial activity. Both treatments were well tolerated throughout the study.
      CONCLUSION: Digen seemed to maintain the properties and activities of each
      individual drug, making it a promising treatment for reducing inflammation after
      phacoemulsification.

PMID- 9278799
TI  - Corneal astigmatism after clear corneal and corneoscleral incisions for cataract
      surgery.
AB  - PURPOSE: To compare the astigmatism induced by clear corneal incisions (CCIs) and
      corneoscleral tunnel incisions (CSIs) for cataract surgery over 6 months.
      SETTING: Rotterdam Eye Hospital, rotterdam, The Netherlands. METHODS: Thirty-five
      patients having phacoemulsification were recruited prospectively; 15 had CCIs and
      20, CSIs. Corneal topography was performed by computerized videokeratoscopy
      preoperatively and 6 months postoperatively. The change in keratometric
      astigmatism was calculated using the absolute magnitude and vector analysis
      methods. RESULTS: There was no significant difference between the change in
      astigmatism produced by the two incisions (Student's t-test). CONCLUSION: The CCI
      for cataract surgery did not produce significantly greater astigmatism than the
      CSI. Concern over CCIs having a greater risk of increasing corneal astigmatism is
      unfounded and does not justify withholding the technique from patients it could
      benefit.

PMID- 9278798
TI  - Control of ocular inflammation after cataract extraction with rimexolone 1%
      ophthalmic suspension.
AB  - PURPOSE: To assess the efficacy and safety of rimexolone 1% ophthalmic suspension
      in controlling intraocular inflammation after cataract extraction. SETTING:
      Twelve independent investigational centers in the United States METHODS: This
      study comprised 197 patients who had cataract extraction. Postoperatively,
      patients were randomized to a 2 week regimen of rimexolone 1% ophthalmic
      suspension or a placebo. Efficacy was analyzed by monitoring total anterior
      chamber cells and flare, other parameters of inflammation, and treatment
      failures. Safety was evaluated by monitoring treatment-related adverse events and
      intraocular pressure (IOP). RESULTS: Rimexolone 1% was clinically and
      statistically more effective in suppressing cell and flare than the placebo (P <
      .02). The overall discontinuation rate for treatment-related adverse events was
      5.3% in the rimexolone group and 22.2% in the placebo group. There were no
      between-group differences in IOP. CONCLUSION: Rimexolone 1% ophthalmic suspension
      was safe and significantly more effective than a placebo in controlling
      intraocular inflammation after cataract extraction when used four times daily and
      continued for 2 weeks.

PMID- 9278800
TI  - Prospective, randomized trial of Microvisc and Healon in routine
      phacoemulsification.
AB  - PURPOSE: To compare the safety and efficacy of the new sodium hyaluronate
      viscoelastic, Microvisc, with those of Healon in routine phacoemulsification.
      SETTING: York Finch Eye Associates and York Finch General Hospital, Toronto,
      Ontario, Canada. METHODS: An unmasked, prospective, randomized clinical trial of
      100 eyes in 100 patients having routine phacoemulsification and intraocular lens
      implantation was conducted to compare the safety and efficacy of Microvisc with
      those of Healon. Visual acuity, corneal thickness, and intraocular pressure were
      assessed preoperatively and at 6 hours, 1 and 5 days, and 1 and 6 months
      postoperatively. RESULTS: There were no statistically significant differences
      between the two treatment groups at any follow-up CONCLUSION: Based on the
      parameters assessed, both viscoelastic products were safe and provided comparable
      outcomes.

PMID- 9278801
TI  - Comparative analysis of the fluidics of the AMO Prestige, Alcon Legacy, and Storz
      Premiere phacoemulsification systems.
AB  - PURPOSE: To compare the mechanism that produces intraoperative intraocular
      pressure (IOP) fluctuations in the AMO Prestige, Alcon Legacy, and Storz Premiere
      with MicroSeal phacoemulsification units. SETTING: In vivo and in vitro portions
      of the study were performed in the operating rooms of Methodist Hospital of
      Indiana. METHODS AND RESULTS: Inflow limits through assembled handpieces of the
      Prestige, Legacy, and Premiere units were measured and tabulated for bottle
      heights of 10 to 100 cm. From identical bottle heights, Prestige inflow limits
      were 50% lower than the Premiere and Legacy limits. Inflow-outflow equilibrium
      pressures, representing steady-state IOP levels in vivo, were physically measured
      in foot position II for the Prestige and Legacy and were directly proportional to
      the inflow limits. The smaller diameter inflow tube on the Prestige handpiece
      resulted in lower steady-state pressures. Amplitude and duration of
      intraoperatively measured IOP fluctuations with the Prestige, Legacy, and
      Premiere units were analyzed and compared. The Prestige ideology tightly monitors
      aspiration and partially substitutes vacuum energy for ultrasonic energy; Legacy
      gears for high flow and tightly monitors vacuum, and Premiere uses the Mackool
      approach to seal the incision. In the Premiere, the fluid volume linked to
      aspiration is enhanced by hydrostatic pressure, most significantly at low
      aspiration levels. Experimental occlusion break surge amplitudes for the Legacy
      were 25% higher and of 50% longer duration than for the Prestige. Comparative
      experimental occlusion break IOP tracings dropped below steady-state pressure
      levels in both systems. Premiere's pressure curves did not dip below steady-state
      pressure levels, leading to the assumption that its noncompliant aspiration
      tubing stores little or no energy and that the flow capacity of its needle is
      approximately 84 cm3/min. In the experimental, as well as surgical, phase of the
      study, flow parameters supporting basic inflow-outflow balancing principles, as
      recommended by each manufacturer, were used in vivo to contrast unit-specific
      performance. CONCLUSION: This study produced quantitative data regarding the
      phacofluidics of three units. Technology improvements have resulted from this
      study.

PMID- 9278802
TI  - Indicators of patient suitability for topical anesthesia.
AB  - PURPOSE: To determine whether a patient's suitability for phacoemulsification
      under topical anesthesia can be predicted preoperatively by their performance
      during tonometry and A-scan. SETTING: Whipps Cross Hospital Ophthalmology
      Department, London, England. METHODS: Fifty consecutive patients who were
      considered suitable for phacoemulsification were selected for the study. Using a
      scoring system we devised, observers assessed the patients for the ease with
      which intraocular pressure and axial length were measured. These scores were
      compared with an assessment of how well they tolerated phacoemulsification under
      topical anesthesia. Correlation between the scores was measured with Spearman's
      rank correlation coefficient, Kendall's rank correlation coefficient, and the
      Goodman-Kruskal gamma statistic. RESULTS: Phacoemulsification and posterior
      chamber intraocular lens implantation were completed in all patients. Statistical
      analysis showed that tonometry and A-scan scores correlated highly with surgery
      scores. Age was also a significant variable in predicting the surgery score. A
      significant discrepancy between tonometry and A-scan and surgery scores was found
      in only one patient, and it was noted that he was one of the youngest patients in
      the study. CONCLUSION: How well a patient performs during tonometry and A-scan
      was a good predictor of how well he or she tolerated having phacoemulsification
      under topical anesthesia. The decision about type of anesthesia should, however,
      also involve other factors, including communication, cooperation, and the age of
      the patient.

PMID- 9278803
TI  - Sedation with ketamine during cataract surgery.
AB  - PURPOSE: To evaluate the cardiovascular and ocular effects of a low-dose sedation
      analgesia regimen in cataract surgery. SETTING: Department of Ophthalmology,
      University of Udine, Udine, Italy. METHODS: Eighty patients were randomly
      assigned to two groups. The first was treated with droperidol 0.03 mg/kg,
      diazepam 0.06 mg/kg, ketamine 0.3 mg/kg; the second (control), with the same
      drugs except for ketamine. Heart rate, arterial pressure, and intraocular
      pressure (IOP) in the fellow eye were measured before and 3 minutes after
      injection of the sedative mixture. The anesthetic block was then performed.
      RESULTS: Heart rate increased in both groups by about 5%. Systolic arterial
      pressure fell by 15.6 mm Hg +/- 22.3 (SD) in the ketamine group and by 31.7 +/-
      17.3 mm Hg (P < .005) in the control group. Intraocular pressure fell in the two
      groups by 5.24 +/- 2.8 mm Hg and 4.5 +/- 2.5 mm Hg, respectively. None of the
      ketamine-treated patients reported pain during the administration of anesthesia
      or postoperatively. Eighty percent of the control group reported pain. In the
      early postoperative period, no episodes of nausea, emesis, or hallucination were
      reported. CONCLUSION: In a regimen with other drugs, ketamine did not influence
      IOP and enabled comfortable completion of anesthesia and surgery.

PMID- 9278804
TI  - Light and scanning electron microscopy of rabbit lens capsules with intraocular
      lenses.
AB  - PURPOSE: To examine postoperative changes in the lens capsules of rabbit eyes
      after phacoemulsification and aspiration of the crystalline lens and implantation
      of posterior chamber intraocular lenses (IOLs) using light and scanning electron
      microscopy. SETTING: Research Laboratory, Department of Ophthalmology, Wakayama
      Medical College, Japan. METHODS: The crystalline lens was emulsified and
      aspirated and an IOL implanted in the capsular bag or ciliary sulcus of each eye
      in adult albino rabbits under general anesthesia. Animals were killed after 4
      weeks, and the lens capsules were removed. The specimens were observed under
      phase-contrast microscopy and processed for light and scanning electron
      microscopy. RESULTS: Phase-contrast microscopy revealed presumed lens epithelial
      cells (LECs) on the central posterior capsules in association with regenerating
      lenticular fibers and Elschnig pearls in the peripheral capsules. Scanning
      electron microscopy showed the accumulation of fibrous extracellular matrix on
      the surface of the posterior capsule in eyes in which the IOL was implanted in
      the ciliary sulcus. Deposition of packed material attached to the surface of IOLs
      and of Soemmering's ring were observed in eyes with in-the-bag IOL fixation. At a
      higher magnification, a parallel arrangement of lenticular fibers was seen in the
      regenerated lens structure on posterior capsules. An identical structure was
      observed under light microscopy. Outgrowth of presumed LECs from residual
      anterior lens capsules and adhesion of macrophages and giant cells were observed
      on the IOL surface. CONCLUSION: Two types of postoperative changes were observed
      in lens capsules after implantation of IOLs: accumulation of fibrous
      extracellular matrix and newly formed lenticular fibers. These changes are
      attributed to the proliferation of LECs and can induce posterior capsule
      opacification after IOL implantation.

PMID- 9278805
TI  - Scleral fixation of an intraocular lens in the absence of capsular support.
AB  - PURPOSE: To ascertain the best surgical technique for fixating an intraocular
      lens (IOL) in the posterior chamber in the absence of capsular support. SETTING:
      From the Institute of Ophthalmology, Pavia University, Pavia, Italy. METHODS:
      Using the SFVT System, the phases of IOL fixation were evaluated in cadaver eyes.
      In addition, IOLs were implanted in the posterior chamber in 340 eyes of patients
      without capsular support. One of several IOL fixation methods was used; IOL power
      was calculated using the same parameters as when the lens is positioned in the
      sulcus. Mean follow-up was 3.5 years (range 2 months to 5 years). RESULTS:
      Intraocular lens placement was accurate only when the loops were positioned in
      the sulcus, with the best approach being internal with suspension sutures placed
      at 3 and 9 o'clock. In most cases, refractive results were good; 152 eyes were
      within +/- 1.00 diopter of the predicted value. CONCLUSION: In eyes without
      capsular support, IOL implantation in the sulcus was possible only when sutures
      were placed exactly through the sulcus. An internal approach using suspension
      sutures at 3 and 9 o'clock gave the best results.

PMID- 9278806
TI  - Incidence of posterior capsular plaque in cataract surgery.
AB  - OBJECTIVE: To determine the incidence of posterior capsular plaque detected
      during cataract surgery, its association with age and type of cataract, and its
      impact on vision. SETTING: Raghudeep Eye Clinic and Iladevi Cataract & IOL
      Research Centre, Ahmedabad, India. METHODS: This prospective study comprised 256
      consecutive eyes having extracapsular cataract extraction with posterior chamber
      intraocular lens implantation. The presence of plaque on the posterior capsule
      was noted and charted. Plaque peeling or posterior capsulorhexis was not done at
      the time of surgery. Mean patient age was 59 years (range 24 to 83 years). Follow
      up was up to 1 year. RESULTS: The overall incidence of plaque was 10.16%. The
      incidence by type of cataract was 5.13%, nuclear sclerotic; 12.50%, posterior
      subcapsular; 9.68%, mixed; 27.27%, mature (P < .05). The difference in incidence
      according to cataract type was highly significant between patients older than 50
      years and those younger than 50 years (P < .001). At the end of 1 year, 61.54% of
      patients with plaque maintained a visual acuity of 20/20 to 20/30; 30.77%, 20/40;
      7.69%, 20/60 or worse. CONCLUSION: The incidence of plaque was higher in eyes
      with mature cataract at any age and in eyes with posterior subcapsular cataract
      in younger patients. Its presence was compatible with reasonable vision at the
      end of 1 year.

PMID- 9278807
TI  - Trauma after radial keratotomy and photorefractive keratectomy.
AB  - A 25-year-old man sustained bilateral ocular trauma from an explosion, which
      resulted in ocular injuries from the blast, mineral projections, and heat. Before
      the accident, the patient had eight-incision radial keratotomy in the left eye
      followed 1 week later by photorefractive keratectomy in the right eye. After the
      accident, the left cornea had a full-thickness rupture of four incisions; the
      fellow cornea had a full-thickness laceration from a mineral projection. Five
      months after the accident, the left eye had an uncorrected visual acuity of
      20/25; the right eye did not achieve an acuity of 20/200 until 20 months after
      the accident.

PMID- 9278808
TI  - Expulsive iridodialysis: an isolated injury after phacoemulsification.
AB  - I report a case of blunt trauma to an eye that had had uneventful
      phacoemulsification through a 5.0 mm self-sealing corneoscleral incision 4 months
      earlier. Total iris expulsion occurred through the cataract incision without
      extension of the wound or disruption of the posterior capsule or intraocular
      lens. A possible mechanism for this injury is discussed and related to the unique
      properties of the corneoscleral incision.

PMID- 9278809
TI  - Macular hemorrhage after excimer laser photorefractive keratectomy.
AB  - We describe three patients with high myopia, 13.0 to 20.0 diopters (D), who had
      typical myopic macular hemorrhages 1 to 6 months after photorefractive
      keratectomy (PRK). The hemorrhages eventually resolved, with resultant permanent
      decrease in vision and pigmentary and atrophic changes in the macula. Highly
      myopic eyes are predisposed to bleeding in areas of lacquer cracks and to myopic
      choroidal neovascularization formation. Awareness of potential retinal pathology
      in patients having PRK and follow-up retinal examinations are warranted.

PMID- 9278810
TI  - Intraocular lens implantation in the pediatric eye.

PMID- 9278811
TI  - Epidemiology of cataract in childhood: a global perspective.
AB  - Cataract is the most important cause of treatable childhood blindness. There are
      an estimated 200,000 children blind from cataract worldwide; 20,000 to 40,000
      children with developmental bilateral cataract are born each year. Rubella is
      still an important cause of preventable disease in many countries. In the
      developing world, there is a need to improve early case detection and referral
      services and to establish centers with expertise in the assessment, surgical
      treatment, and long-term management of the child with cataract.

PMID- 9278812
TI  - Intraocular lens implantation in infant monkeys: clinical and histopathological
      findings.
AB  - PURPOSE: To determine the long-term effects of intraocular lens (IOL)
      implantation in infant monkey eyes. SETTING: Yerkes Regional Primate Research
      Center, Emory University School of Medicine, Atlanta, Georgia, USA. METHODS: A
      30.00 diopter (D), all-poly(methyl methacrylate) IOL with an overall diameter of
      10.0 mm was implanted in the right eye of 11 infant monkeys. Seven monkeys
      developed postoperative complications and were not followed on a long-term basis.
      However, 4 monkeys were followed clinically for 4 1/2 years, after which their
      pseudophakic eyes were examined histopathologically. RESULTS: The final
      refractive error in the four pseudophakic eyes with long-term follow-up ranged
      from -4.75 to +0.75 D. Three of the four eyes had a Soemmering's ring. Only one
      haptic was in the capsular bag. whereas five had eroded into the iris
      root/ciliary body. The corneas and posterior segments of the eyes were normal.
      CONCLUSION: Two-thirds of the eyes having neonatal IOL implantation experienced
      significant postoperative complications. Haptic location was suboptimal in all
      four eyes followed for 4 1/2 years. The diameter of the IOLs implanted in these
      eyes was probably too large. Some of these complications might have been averted
      by implanting an IOL with a smaller diameter.

PMID- 9278813
TI  - Epilenticular lens implantation versus extracapsular cataract extraction and lens
      implantation in children.
AB  - PURPOSE: To compare the results of epilenticular posterior chamber intraocular
      lens (IOL) implantation and pars plana lensectomy with those of extracapsular
      lens aspiration and posterior chamber IOL implantation in eyes with pediatric
      cataracts. SETTING: Guru Nanak Eye Centre, New Delhi, India. METHODS: Forty eyes
      with childhood cataract of varied etiology were divided into two groups of 20
      eyes each, matched by age, sex, and type of cataract. Group A had epilenticular
      IOL implantation with pars plana lensectomy. Group B had extracapsular lens
      aspiration with posterior chamber IOL implantation. Follow-up ranged from 1 to 3
      years. RESULTS: All 20 eyes in Group A maintained a clear pupillary axis from the
      immediate postoperative period to the last follow-up. In Group B, 80% of eyes
      developed varying degrees of posterior capsule opacification (PCO), which
      hampered vision. In Group A, 95% of eyes had a visual acuity of 6/12 or better;
      only 45% of eyes in Group B achieved a visual acuity of 6/60 or better.
      CONCLUSION: Although patients in both groups had good visual recovery, those
      having epilenticular IOL implantation with pars plana lensectomy maintained a
      clear pupillary axis and did not develop PCO, preventing the need for secondary
      intervention.

PMID- 9278814
TI  - Choice of lens and dioptric power in pediatric pseudophakia.
AB  - PURPOSE: To evaluate lens choice and dioptric power in pediatric eyes having
      posterior chamber intraocular lens (IOL) implantation. SETTING: Oxford Eye Center
      and the St. John Eye Hospital, Johannesburg, South Africa. METHODS: This
      retrospective study evaluated the refractive development in 156 pseudophakic eyes
      of 99 children aged 1 month to 8 years who had surgery between June 1983 and
      April 1994. The children were divided into three groups based on age at time of
      IOL implantation: Group A (68 eyes), 1 to 18 months; Group B (32 eyes), 19 to 36
      months; Group C (48 eyes), 3 to 8 years. Poly(methyl methacrylate) posterior
      chamber IOLs with an overall diameter between 10.5 and 12.0 mm were used. The
      dioptric power was 3.00 to 6.00 diopters (D) less than that needed to achieve
      emmetropia. RESULTS: In Group A, the mean growth in axial length was 3.59 mm +/-
      1.80 (SD) and the mean change in refraction was 6.39 +/- 3.68 D. In Group B, the
      respective means were 0.75 +/- 0.85 mm and 2.73 +/- 1.40 D and in Group C, 0.76
      +/- 0.69 mm and 2.60 +/- 1.84 D. CONCLUSIONS: The younger the child at time of
      implantation, the greater the myopic shift. To reduce the necessity of IOL
      exchange, these eyes should be undercorrected, with the residual refractive error
      corrected by spectacles that are adjusted throughout life according to refractive
      development. This leads to initial hypermetropia that gradually moves to
      emmetropia or moderate myopia in adulthood.

PMID- 9278815
TI  - Longitudinal changes in axial length in pseudophakic children.
AB  - PURPOSE: To evaluate the axial length changes that occur in children 3 to 9 years
      of age who had cataract extraction with primary intraocular lens (IOL)
      implantation. SETTING: Emory Eye Center, Emory University, and Egleston
      Children's Hospital, Atlanta, Georgia, USA. METHODS: A review of 17 eyes in 15
      children (mean age 6.4 years; range 3 to 9 years) who had primary IOL
      implantation was undertaken. Patients were followed for an average of 3.1 years.
      The initial and final axial length measurements and refractive errors were
      compared. RESULTS: The overall change in mean axial length in the 17 eyes was
      0.64 mm. The overall mean myopic shift was -1.01 diopters (D) (range -3.00 +0.50
      D). Eyes with traumatic cataracts experienced more axial elongation than eyes
      with developmental/congenital cataracts (0.97 mm versus -0.01 mm; P = .03).
      Ninety-four percent of patients obtained a final visual acuity of 20/40 or
      better. CONCLUSION: Eyes with traumatic cataracts experienced more axial
      elongation than eyes with developmental/congenital cataracts after cataract
      extraction and IOL implantation.

PMID- 9278816
TI  - Ocular growth in newborn rabbit eyes implanted with a poly(methyl methacrylate)
      or silicone intraocular lens.
AB  - PURPOSE: To examine eye growth in lensectomized infant rabbits implanted with a
      poly(methyl methacrylate) (PMMA) or a silicone intraocular lens (IOL). SETTING:
      S:t Eriks Eye Hospital, Karolinska Institute, Stockholm, Sweden. METHODS: Two
      groups of 3-week-old rabbits were used. In Group 1 (n = 13), lensectomy was
      performed in both eyes. In one randomly selected eye, a +30 diopter (D) heparin
      surface-modified (HSM) PMMA IOL was implanted in the capsular bag; the other eye
      was left aphakic. In Group 2 (n = 10), a +21 D HSM PMMA IOL was implanted in one
      randomly selected eye and a +21 D silicone IOL was implanted in the other. Axial
      length, corneal diameter, corneal thickness, and intraocular pressure (IOP) were
      measured in all eye preoperatively and 1, 2, and 3 months after surgery. The wet
      mass of the after-cataract was measured 3 months after surgery. The ciliary body
      with the ciliary processes and the peripheral retina were examined histologically
      after formalin fixation. The two IOL types were compressed to 7.0 MM,
      corresponding to the diameter of the 3-week-old rabbit lens. RESULTS: In Group 1,
      the axial length was significantly decreased in the eye with an HSM PMMA IOL
      compared with the fellow aphakic eye (P < .01, two-way analysis of variance
      [ANOVA]). No significant difference in corneal diameter, corneal thickness, or
      IOP was found between the eyes. The wet mass of the dissected after-cataract was
      significantly less in the eye implanted with an IOL. Two animals had an elevated
      IOP with secondary glaucoma in their aphakic eye and were excluded from the
      study. In Group 2, axial length in eyes with the HSM PMMA IOL was less than in
      the eyes with the silicone IOL (P < .25, two-way ANOVA). No difference in corneal
      diameter, corneal thickness, or IOP was found. The amount of after-cataract was
      not altered. Histologically, the eyes with the HSM PMMA IOL showed retinal
      degeneration, neovascularization of the ciliary body accompanied by a large
      number of inflammatory cells, and tumid ciliary processes. The eyes with the
      silicone IOL showed only minor changes. The aphakic eyes presented even less
      histological change. The compression test demonstrated that three time the
      compression force was needed to squeeze the HSM PMMA lens than the silicone IOL.
      CONCLUSION: The results suggest that in the young rabbit eye, implanting a
      regular size HSM PMMA IOL destroys intraocular tissues and reduces eye growth
      significantly. Replacing the PMMA IOL with a silicone IOL improves the ocular
      growth.

PMID- 9278817
TI  - After-cataract and ocular growth in newborn rabbit eyes implanted with a capsule
      tension ring.
AB  - PURPOSE: To examine after-cataract and eye growth in lensectomized newborn
      rabbits implanted with capsule tension rings of different sizes. SETTING: S:t
      Eriks Eye Hospital, Karolinska Institute, Stockholm, Sweden. METHODS: Two groups
      of 24-day-old rabbits were used. In Group 1 (n = 9), lensectomy was performed in
      both eyes. In one randomly selected eye, an open poly(methyl methacrylate) (PMMA)
      capsule tension ring with a 7.0 mm diameter and 0.13 mm thickness was implanted
      in the capsular bag. The other eye was left aphakic. In Group 2 (n = 10), an open
      PMMA capsule tension ring with a 10.0 mm diameter and 0.13 mm thickness was
      implanted in one randomly selected eye, and the other eye was left aphakic. Axial
      length, corneal diameter, corneal thickness, and intraocular pressure (IOP) were
      measured in all eyes preoperatively and 1, 2, and 3 months after surgery. The wet
      mass of the after-cataract was measured at 3 months. Three Group 1 eyes and four
      Group 2 eyes developed secondary glaucoma and were excluded from the study.
      RESULTS: Axial growth did not differ significantly between the eyes implanted
      with the 7.0 mm ring and the aphakic eyes (mean difference 0.01 mm; F3;15 = 0.02;
      P > .25). Corneal diameter also did not differ (two-way analysis of variance
      [ANOVA]). Axial length growth was less in the eyes implanted with the 10.0 mm
      ring than in the aphakic eyes (mean difference 1.05 mm; F3;15 = 2.06; P < .25).
      The average decrease in corneal diameter growth was 1.0 mm in the implanted eyes.
      Growth in the eyes with the 10.0 mm ring was significantly less than in the eyes
      with the 7.0 mm ring (P = .05, Wilcoxon rank-sum test). Corneal thickness and IOP
      did not differ significantly between eyes (F3;15 = 0.6; P > .25; two-way ANOVA).
      Amount of after-cataract did not differ significantly between the aphakic eyes
      and the eyes implanted with the 7.0 mm ring. It was significantly less in the
      eyes with the 10.0 mm ring than in those with the 7.0 mm ring (Wilcoxon signed
      rank test) and in the aphakic eyes (P < .025, Wilcoxon rank-sum test).
      CONCLUSION: In the young rabbit eye, a 10.0 mm capsule ring reduced the eye
      growth compared with both the aphakic eye and the eye implanted with a 7.0 mm
      ring. The 10.0 mm ring also inhibited the production of after-cataract compared
      with the production in the aphakic eye and the eye implanted with the 7.0 mm
      ring.

PMID- 9278818
TI  - Radiofrequency diathermy capsulorhexis of the anterior and posterior capsules in
      pediatric cataract surgery: preliminary results.
AB  - PURPOSE: To assess the effectiveness of radiofrequency diathermy capsulorhexis in
      preventing opacification of the posterior capsule in pediatric cataract
      extraction. SETTING: The Children's Hospital, Dublin, Ireland. METHODS:
      Radiofrequency diathermy capsulorhexis to the anterior capsule followed by
      injection of sodium hyaluronate behind the posterior capsule and primary
      posterior capsule diathermy capsulorhexis were performed in 14 eyes of 7 children
      requiring cataract surgery. RESULTS: Six patients had bilateral congenital and 1
      patient bilateral developmental cataracts. Ten eyes (5 patients) received heparin
      surface-modified intraocular lenses, and 4 eyes (2 patients) were left aphakic.
      There were no intraoperative complications, and only mild anterior segment
      inflammation was noted postoperatively. CONCLUSION: With follow-up from 7 to 16
      months (mean 12.1 months), our results showed no epithelial regrowth or
      opacification of the posterior capsule following diathermy capsulorhexis.

PMID- 9278819
TI  - Primary posterior capsulorhexis with and without anterior vitrectomy in
      congenital cataracts.
AB  - PURPOSE: To determine whether anterior vitrectomy is necessary along with primary
      posterior capsulorhexis in children less than 5 years of age with congenital
      cataracts. SETTING: Iladevi Cataract & IOL Research Centre, Ahmedabad, India.
      METHOD: This prospective study comprised 18 eyes of 16 children whose mean age
      was 2.3 years (range 3 months to 5 years). Primary posterior continuous
      curvilinear capsulorhexis (PCCC) and posterior chamber intraocular lens (IOL)
      implantation were performed in all eyes. No vitrectomy was done in 8 eyes (Group
      1); an anterior vitrectomy was performed in 10 eyes (Group 2). Optic capture
      through the posterior capsule was achieved in 3 eyes in Group 1 and in 5 eyes in
      Group 2. Average follow-up was 13.3 months. RESULTS: Five eyes (62.5%) in Group 1
      needed secondary pars plana vitrectomy because the visual axis was obscured; no
      eye in Group 2 needed a secondary procedure. Four Group 1 eyes developed
      significant complications (updrawn pupil, decentration, occlusio pupillae,
      transient glaucoma). While no Group 2 eye developed a serious complication, some
      degree of pigment dispersion was noted in all the eyes. CONCLUSION: The results
      suggest that anterior vitrectomy is desirable along with primary PCCC in children
      younger than 5 years with congenital cataracts.

PMID- 9278820
TI  - Posterior continuous curvilinear capsulorhexis and optic capture of the
      intraocular lens to prevent secondary opacification in pediatric cataract
      surgery.
AB  - PURPOSE: To evaluate the safety and efficacy of posterior continuous curvilinear
      capsulorhexis with optic capture n preventing secondary opacification of the
      visual axis in pediatric eyes having cataract surgery and intraocular lens (IOL)
      implantation. SETTING: Gimbel Eye Centre, Calgary, Alberta, Canada. METHOD:
      Posterior continuous curvilinear capsulorhexis with optic capture of the IOL was
      performed in 18 of 19 consecutive pediatric cataract patients (ages 2 1/2 to 12
      years). Heparin-coated IOLs with 6 degree angulation of the haptics were
      implanted in all eyes. Only eyes with a minimum of 18 months follow-up (n = 16)
      were analyzed. RESULTS: Mean follow-up in the 16 eyes was 35.5 months +/- 9.45
      (SD), ranging from 19 to 49 months. To date, the visual axis has remained clear
      in all eyes. No anterior vitrectomy was purposefully performed in any eye.
      CONCLUSION: Posterior continuous curvilinear capsulorhexis with optic capture of
      the heparin-coated IOL appeared to successfully prevent secondary opacification
      of the visual axis in pediatric cataract cases.

PMID- 9278821
TI  - Retrospective comparison of techniques to prevent secondary cataract formation
      after posterior chamber intraocular lens implantation in infants and children.
AB  - PURPOSE: To determine the effect of various methods of managing the posterior
      capsule and anterior vitreous on the rate of posterior capsule opacification in
      pediatric eyes implanted with posterior chamber intraocular lenses (PC IOLs).
      SETTING: Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, USA.
      METHODS: We reviewed the charts of 20 eyes of 15 children (aged 1.5 to 2 years)
      who had primary cataract surgery with PC IOL implantation during the past 5
      years. The posterior capsule and anterior vitreous were managed in a variety of
      ways: In 5 eyes, the posterior capsule was left intact; in 15 eyes, a posterior
      continuous curvilinear capsulorhexis (PCCC) was performed - 6 with and 9 without
      anterior vitrectomy; in 8 eyes, posterior optic capture was performed - 3 with
      and 5 without vitrectomy. The follow-up ranged from 1 to 4.5 years (mean 2
      years). RESULTS: Visually significant secondary cataract developed in the five
      eyes with intact posterior capsules and in the four eyes that had PCCC without
      vitrectomy and without posterior optic capture (i.e., the optic was left in the
      capsular bag). The optical axis remained clear in the six eyes that had PC IOL
      implantation with vitrectomy (with or without posterior optic capture).
      Initially, all eyes that had optic capture without vitrectomy also remained
      clear, but after 6 months, four of five developed opacification. CONCLUSION: In
      this series, PCCC with anterior vitrectomy was the only effective method of
      preventing or delaying secondary cataract formation in infants and children.

PMID- 9278822
TI  - Review of aphakic glaucoma after surgery for congenital cataract.
AB  - This article describes the clinical presentation of glaucoma in eyes operated on
      for congenital cataract and reviews current theories as to its pathophysiology.
      The literature does not provide a conclusive explanation for the seeming increase
      in aphakic glaucoma in children. Long-term studies comparing like groups may help
      resolve this question.

PMID- 9278823
TI  - Glaucoma after cataract extraction and posterior chamber lens implantation in
      children.
AB  - PURPOSE: To evaluate the incidence of postoperative glaucoma in children who have
      cataract extraction and posterior chamber intraocular lens (IOL) implantation.
      SETTING: Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
      METHODS: The incidence of glaucoma of all etiologies was evaluated in 45 eyes of
      37 selected consecutive patients aged 1 to 18 years who had cataract extraction
      and posterior chamber IOL implantation from 1991 to 1994. Mean follow-up was 23
      months (range 6 to 38 months). Nineteen patients had traumatic and 18 had
      developmental cataract. Exclusion criteria were microcornea smaller than 9.0 mm
      in diameter, preoperative glaucoma, or poor pupil dilation. The surgical
      technique comprised a continuous curvilinear anterior capsulorhexis in most
      cases, extracapsular aspiration by Ocutome or phacoemulsification, and retention
      of the posterior capsule. A peripheral iridectomy was done in 7 eyes (16%).
      Postoperative medications included topical atropine combined with topical,
      subconjunctival, and systemic corticosteroids and antibiotics. RESULTS: Three
      patients with traumatic cataract developed postoperative glaucoma during the
      follow-up. One developed pseudophakic pupillary block; however, a peripheral
      iridectomy prevented glaucoma. Two other patients developed late-onset glaucoma:
      one secondary to angle recession and the other to peripheral anterior synechias.
      No patient with developmental cataract developed glaucoma. CONCLUSION: Careful
      patient selection, atraumatic surgical technique, continuous curvilinear
      capsulorhexis, in-the-bag IOL placement, postoperative atropine, and topical and
      systemic corticosteroids significantly lower the incidence of pseudophakic
      pupillary block and glaucoma. Although no patient developed glaucoma, lifelong
      follow-up is mandatory to detect chronic open-angle and traumatic angle-recession
      glaucoma.

PMID- 9278824
TI  - Secondary capsule-supported intraocular lens implantation in children.
AB  - PURPOSE: To evaluate surgical problems, postoperative complications, and visual
      results of secondary posterior chamber intraocular lens (IOL) implantation in
      children. SETTING: L.V. Prasad Eye Institute, Hyderabad, India. METHODS: A
      retrospective study was done of secondary IOL implantation in 27 children (35
      eyes) who were not satisfied with aphakic glasses and were intolerant of or
      reluctant to use contact lenses. The extent of posterior capsular support was
      assessed prior to surgery. Additional surgical procedures were posterior
      synechiolysis (11 eyes), anterior vitrectomy (8 eyes), pupilloplasty (2 eyes),
      and membranectomy (2 eyes). RESULTS: Postoperative complications included wound
      leak (1 eye), uveitis (5 eyes), peripheral anterior synechias (2 eyes), and
      retinal detachment (1 eye). Visual acuity improved or remained at the
      preoperative level in 34 eyes. CONCLUSION: Secondary posterior chamber IOL
      implantation is an effective optical modality for managing pediatric aphakia.
      Observation must continue to determine the long-term safety of the procedure.

PMID- 9278825
TI  - Management of traumatic cataract in children.
AB  - PURPOSE: To evaluate the presentation, mode of management, and clinical outcome
      of traumatic cataract in children. SETTING: L.V. Prasad Eye Institute, Hyderabad,
      India. METHODS: One hundred thirty-seven children (< 16 years) who developed
      traumatic cataract, seen between January 1988 and December 1993, were
      retrospectively analyzed. Nature of injury, type of cataract, management, and
      outcome were evaluated. RESULTS: The study group comprised 110 boys and 27 girls.
      Average follow-up was 11.7 months (range 1 week to 60 months). Most injuries
      (54.7%) were caused by a stick or a bow and arrow. Most (53.2%) of the cataracts
      were total. Corneal scarring (60.5%) and iris-related problems (49.6%) were the
      most common associated findings. Extracapsular cataract extraction with
      intraocular lens (IOL) implantation was performed in 65.67% of patients. Visual
      acuity improved form 20/200 or worse in 97.7% of patients preoperatively to 20/60
      or better in 74.1% or patients postoperatively. Seventeen patients had associated
      posterior segment insult; most failed to recover satisfactory vision. Posterior
      capsule opacification (PCO) was noted in 42.9% of patients. CONCLUSIONS:
      Extracapsular cataract extraction with IOL implantation provides satisfactory
      results in children with traumatic cataract. Associated posterior segment
      complications and development of PCO are the major obstacles to visual
      rehabilitation.

PMID- 9278826
TI  - Preoperative evaluation: a shared vision for change.

PMID- 9278827
TI  - Unindicated preoperative testing: ASA physical status and financial implications.
AB  - STUDY OBJECTIVE: To determine if the ordering of unindicated preoperative
      laboratory tests is different for healthy (ASA physical status I and II) versus
      sicker (ASA physical status III) patients, and to examine the financial
      implications at our institution of unindicated preoperative testing. DESIGN:
      Prospective, cross-sectional study. SETTING: University hospital. PATIENTS: 383
      consecutive patients scheduled for elective surgery and seen by an
      anesthesiologist in the Preoperative Clinic. Complete data was available for 312
      patients. MEASUREMENTS AND MAIN RESULTS: Preoperative laboratory tests ordered by
      the surgeon were compared to those tests considered indicated by one of several
      anesthesiologists for ASA physical status I and II versus ASA physical status III
      patients. An average of 72.5% of tests ordered by surgeons were considered not
      indicated by the anesthesiologists. ASA physical status III patients had
      significantly fewer unindicated complete blood count, platelet count, prothrombin
      time, partial thromboplastin time, chemistry 12 profile, and chest radiography
      orders than did ASA physical status I and II patients. Our hospital could
      generate approximately $80,000 in variable and semifixed cost savings by
      eliminating these unindicated preoperative tests for the 5,100 patients seen in
      Preoperative Clinic annually (29% of the total surgical patients). CONCLUSIONS: A
      large percentage of preoperative tests ordered by surgeons at our institution are
      not indicated. Eliminating unindicated tests would cut hospital revenues in a
      climate where testing is fee-for-service and would save the hospital money in a
      managed-care or capitated system.

PMID- 9278828
TI  - Perioperative hypercoagulability in uremic patients: a viscoelastic study.
AB  - STUDY OBJECTIVE: To examine whole blood coagulation in uremic patients presenting
      for surgery with the thromboelastogram and the Sonoclot analyzer. DESIGN:
      Prospective, observational study. SETTING: Operating rooms of a university
      affiliated hospital. PATIENTS: 30 ASA physical status II and III patients with
      chronic renal failure, and 30 age-matched and gender-matched patients with normal
      renal function, presenting for elective surgery. INTERVENTIONS: Blood sampling
      for thromboelastograph and Sonoclot analysis immediately after anesthetic
      induction, prior to surgical incision. MEASUREMENTS AND MAIN RESULTS:
      Thromboelastographic indices of coagulation, reflecting coagulation factor
      function (R time), fibrinogen-platelet interaction (K time and alpha angle), and
      qualitative platelet function (maximum amplitude) were hypercoagulable in the
      uremic group compared with the control group (p < 0.05). Fibrinolysis (%) was
      decreased in the uremic group (p < 0.05). Fibrin formation (initial slope) and
      platelet function (time to peak) of the Sonoclot trace also were hypercoagulable
      in the uremic group (p < 0.05). CONCLUSIONS: The high incidence of arteriovenous
      graft and fistulae thromboses in uremic patients belies in vitro laboratory
      evidence of platelet dysfunction. We have demonstrated perioperative
      hypercoagulability in uremic patients with viscoelastic measures of whole blood
      coagulation. These data suggest that traditional concern for coagulopathy and
      platelet dysfunction in uremic patients may require re-assessment in light of
      this "pro-thrombotic" state.

PMID- 9278829
TI  - Prolonged surgery increases the likelihood of admission of scheduled ambulatory
      surgery patients.
AB  - STUDY OBJECTIVE: To identify variables influencing the likelihood of
      unanticipated admission following scheduled ambulatory surgery. DESIGN:
      Retrospective case-controlled chart review study. SETTING: A large academic
      tertiary care hospital. PATIENTS: 8,549 ASA physical status I, II, III, and IV
      patients who underwent scheduled ambulatory surgery in 1991. MEASUREMENTS AND
      MAIN RESULTS: Of the 8,549 patients, 216 were admitted, with complete medical
      record information available for 167 of the admitted patients. The most common
      reasons for admission among the 167 were surgical (43%), anesthetic (28%), and
      medical (17%) complications. Odds for admission following long surgery (of at
      least 60 minutes) were 7.5 times (p < 0.001) greater than following short surgery
      (under 60 minutes). Among long cases, independent variables influencing admission
      were: general anesthesia [odds ratio 20.8; 95% confidence interval (CI) 4.4 to
      45.6], and monitored anesthesia care or regional anesthesia (combined odds ratio
      8.3; 95% CI 1.7 to 40.8). ASA physical status and patient age did not
      significantly influence admission rate for long cases. For short cases, patients
      over 65 years (odds ratio 5.6; 95% CI 2.6 to 12.0), ASA physical status III or IV
      (odds ratio 4.8; 95% CI 2.0 to 11.6), use of general anesthesia (odds ratio 4.7;
      95% CI 1.5 to 14.2), and monitored anesthesia care or regional anesthesia (odds
      ratio 3.1; 95% CI 1.0 to 10.1) independently influenced the likelihood of
      admission. Type of surgery and gender had no detectable effect on admission.
      CONCLUSIONS: Surgery duration of 60 minutes or longer was the most important
      predictor of unanticipated admission following scheduled ambulatory surgery.

PMID- 9278830
TI  - Ondansetron versus droperidol or placebo when given prophylactically for the
      prevention of postoperative nausea and vomiting in patients undergoing middle ear
      procedures.
AB  - STUDY OBJECTIVE: To compare the prophylactic administration of ondansetron with
      droperidol or placebo to determine its effectiveness in reducing postoperative
      nausea and vomiting after middle ear procedures. DESIGN: Prospective, randomized,
      double-blind study. SETTING: Inpatient otolaryngology service at a university
      medical center. PATIENTS: 120 ASA physical status I and II patients presenting
      for elective middle ear surgical procedures. INTERVENTIONS: Patients were
      randomly assigned to receive either placebo (Group 1), ondansetron 4 mg
      intravenously (IV) (Group 2), or droperidol 25 mcg/kg i.v. (Group 3) 10 minutes
      before induction of general anesthesia using thiopental 5 mg/kg i.v. with
      fentanyl 2 mcg/kg i.v. and maintenance anesthesia with isoflurane 1% to 2% end
      tidal in a 50% air/oxygen mixture. MEASUREMENTS AND MAIN RESULTS: Total surgical,
      anesthesia, extubation, and postanesthesia care unit (PACU) occupancy times were
      recorded along with anesthesia recovery scores. The incidence and severity of
      nausea, vomiting, and pain along with rescue antiemetic administration, also were
      recorded. Similar assessments were made over the next 24 hours. Intergroup
      demographic data were similar except that the male to female ratio was higher in
      the ondansetron group. Stewart scores, reflecting emergence from anesthesia, were
      higher with ondansetron compared with droperidol. The incidence of nausea was
      similar between the groups but the severity was less after ondansetron therapy.
      More patients vomited after placebo than when given either droperidol or
      ondansetron. No intergroup differences were noted in the use of rescue
      antiemetics. Twenty-four hours later, more patients who received the placebo drug
      had nausea or vomited compared with either ondansetron or droperidol.
      CONCLUSIONS: Ondansetron 4 mg i.v. is as effective as droperidol and better than
      placebo in preventing nausea and vomiting in patients undergoing middle ear
      surgery. No cost advantage as determined by lower use of rescue antiemetics or
      shorter PACU times was noted after the prophylactic administration of
      ondansetron.

PMID- 9278831
TI  - Removal of retained air during cardiac surgery with transesophageal
      echocardiography and capnography.
AB  - STUDY OBJECTIVE: To evaluate a new method for removal of retained air at the end
      of cardiopulmonary bypass (CPB) by end-tidal CO2 pressure (PETCO2) and pulmonary
      arterial pressure (PAP) monitoring, and transesophageal two-dimensional
      echocardiography (TEE). DESIGN: Prospective study. SETTING: Cardiac surgery unit
      at a university hospital. PATIENTS: 36 ASA physical status I, II, III patients
      for open heart surgery. INTERVENTIONS: The CPB reservoir was gradually raised to
      decrease venous drainage. Accordingly, the right heart began to receive the
      venous blood and eject it to the pulmonary artery. The vent existing in the left
      ventricle or the left atrium then collected any whole blood containing air
      bubbles that came from the pulmonary circulation. The air bubbles were confirmed
      by TEE to be removed and not to eject from the left ventricle to te systemic
      circulation. MEASUREMENTS AND MAIN RESULTS: Levels of PETCO2, PaCO2, PAP, and the
      duration of the removal procedure were measured when a sufficient pulmonary
      circulation was established and the removal of retained air was considered to be
      satisfactorily accomplished by the absence of air bubbles, confirmed by TEE for
      more than 30 seconds. PETCO2 reached 28 +/- 4 mmHg during the removal of air,
      while PaCO2 reached 35 +/- 6 mmHg (p < 0.05). Mean PAP during removal of air
      reached 18 +/- 4 mmHg, which was approximately 90% of that before CPB. The
      duration time of removal of air was 9 +/- 2 min. CONCLUSIONS: PETCO2 and PAP are
      useful indicators of pulmonary circulation during this procedure for removal of
      air. PETCO2 of 25 to 30 mmHg and PAP of 90% of the prebypass level have been
      found to be necessary for the removal of air. Our technique for removal of air
      using PETCO2, PAP, and TEE enables us to satisfactorily eliminate residual air.

PMID- 9278832
TI  - Reduction of propofol injection pain with a double lumen i.v. set.
AB  - STUDY OBJECTIVE: To investigate if the use of a new double lumen i.v. set (DLIS)
      decreases the incidence of propofol injection pain compared with single lumen
      i.v. set (SLIS) administration. DESIGN: Prospective, randomized, double-blinded
      study. SETTING: Operating rooms in a university hospital. PATIENTS: 50 adult ASA
      physical status I and II patients of both genders undergoing general anesthesia
      for elective surgery. INTERVENTIONS: Patients were injected with propofol either
      through a DLIS or a SLIS. MEASUREMENTS AND MAIN RESULTS: Three different pain
      indices were recorded to be present or absent: (1) verbal report of pain during
      propofol injection (2) grimacing during propofol injection, and (3) recall of
      injection pain in the recovery room. When the DLIS was used, the incidence of
      verbal pain, grimacing during propofol injection, and recall of pain during
      recovery were lowered significantly by 53%, 46%, and 52%, respectively (chi
      square analysis of contingency table with Yates correction, p < 0.05).
      CONCLUSIONS: The DLIS significantly reduced the incidence of propofol injection
      pain compared with SLIS. Further studies are indicated to evaluate the cost
      effectiveness of this device.

PMID- 9278833
TI  - Desire for perioperative information in adult patients: a cross-sectional study.
AB  - STUDY OBJECTIVE: To identify which perioperative information outpatients want
      from their anesthesiologist. DESIGN: Cross-sectional study. SETTING: Outpatient
      center. PATIENTS: 197 ASA physical status I and II patients undergoing outpatient
      surgery. INTERVENTIONS: A questionnaire examining for "desire for information".
      MEASUREMENTS AND MAIN RESULTS: Demographic data including age, ethnicity, gender,
      socioeconomic status, and history of previous surgery were obtained. Trait,
      situational anxiety, and coping strategy were assessed using a validated
      behavioral instrument and a questionnaire adopted from previous studies conducted
      in Australia, Scotland, and Canada. Each questionnaire contained 14 statements
      regarding specific perioperative details. An index of the overall patient desire
      for information (PDI) was calculated for each subject. More than 85% of subjects
      gave a high priority to being informed for all the 14 items. Scores on the
      overall index were found to be higher for females than for males (32 +/- 6 vs. 30
      +/- 6; p = 0.03), and this finding persisted in a multivariable model that also
      included coping strategies and anxiety (DF = 1,175, F = 4.6, p = 0.01). Subjects
      also had higher PDI scores if a first degree relative had a history of previous
      surgery (33 +/- 5 vs. 31 +/- 6; p = 0.007). On analysis of individual
      questionnaire items, Latino Americans were significantly less likely than
      European Americans or African Americans to desire perioperative information (p <
      0.05). Similarly, females had a significantly higher desire for information than
      males. Subjects who were divorced demonstrated a higher desire for information
      than did single or married subjects. CONCLUSIONS: Ethnicity, gender, coping
      mechanism, marital status, and a history of previous surgery in a relative have
      been identified as predictors for the desire for information.

PMID- 9278834
TI  - Intrathecal neostigmine for postoperative analgesia after orthopedic surgery.
AB  - STUDY OBJECTIVE: To establish a dose-response curve for the analgesic effect of
      intrathecal neostigmine in patients undergoing below knee surgery with spinal
      anesthesia. To assess adverse effects, principally nausea and vomiting. DESIGN:
      Randomized, double-blind, prospective study. SETTING: Teaching hospital.
      PATIENTS: 60 ASA physical status I and II premedicated patients undergoing
      orthopedic surgery (tibial or ankle reconstruction). INTERVENTION: Spinal
      anesthesia was performed at the sitting position, L3-L4 interspace, 4 ml final
      volume, injected at a rate of 1 ml/10 sec. The control group (CG) received 15 mg
      hyperbaric bupivacaine 0.5% plus saline. The 25 micrograms neostigmine group
      (25NG) received 15 mg hyperbaric bupivacaine plus 25 micrograms neostigmine; the
      50 micrograms neostigmine group (50NG) received 15 mg hyperbaric bupivacaine plus
      50 micrograms neostigmine; and the 100 micrograms neostigmine group (100NG)
      received 15 mg hyperbaric bupivacaine plus 100 micrograms neostigmine. Patients
      were placed supine after the spinal punction. MEASUREMENTS AND MAIN RESULTS: Time
      to first rescue analgesics, analgesia, and adverse effects at constant intervals
      were assessed using the 10 cm visual analog scale (VAS). Intrathecal neostigmine
      produced a dose-independent reduction in the postoperative rescue analgesic
      consumption (p < 0.0001). The time to first rescue analgesics was similar among
      groups (p > 0.05), and the overall 24-hour VAS pain scores were lowest for
      patients who had spinal neostigmine (p < 0.02). The 100NG group had the highest
      incidence of postoperative nausea and vomiting of all the groups (p < 0.05).
      CONCLUSION: Intrathecal neostigmine produced a dose-independent analgesia and a
      dose-dependent incidence of adverse effects with the doses studied.

PMID- 9278835
TI  - Assessment of the economic impact of an overage reduction program in the
      operating room.
AB  - STUDY OBJECTIVES: To delineate excessive supply preparation in the operating
      rooms (ORs) of Yale-New Haven Hospital, and to measure the reduction in such
      overage as a result of nursing and administration cost-containment efforts.
      DESIGN: Before and after trial. SETTING: Inpatient ORs of Yale-New Haven
      Hospital. INTERVENTIONS: After the initial documentation of overage, several cost
      containment measures were instituted, including nursing education, review of
      overage data, and updating of surgical request lists. MEASUREMENTS AND MAIN
      RESULTS: The hospital cost of case-specific overage generated by all surgical
      procedures performed during two 2.5-month periods in 1992 and 1994 (before and
      after the interventions) were compared. One-thousand three hundred eighteen cases
      in 1992 were compared with 1,367 cases in 1994. A 45% reduction in mean per case
      overage occurred between the two assessment periods. Extrapolation of the data to
      the incidence of similar cases throughout the United States projected a
      comparable savings. CONCLUSIONS: Efforts to increase the efficiency of OR supply
      management can be measured, in part, by overage evaluation, which can serve as a
      resource for focusing efforts at cost-containment.

PMID- 9278836
TI  - Active warming, not passive heat retention, maintains normothermia during
      combined epidural-general anesthesia for hip and knee arthroplasty.
AB  - STUDY OBJECTIVE: to compare passive heat retention by low-flow anesthesia, alone
      and with additional thermal insulation by reflective blankets, with forced-air
      warming preventing intraoperative hypothermia during combined epidural-general
      anesthesia. DESIGN: Randomized, controlled study. SETTING: Inpatient anesthesia
      at a university department of orthopedic surgery. PATIENTS: 30 ASA physical
      status I and II patients, who were scheduled for elective hip or knee
      arthroplasty and were free from systemic disease. INTERVENTIONS: Patients
      received epidural block up to T10 by alkalinized lidocaine 2%, and then were
      administered standard general anesthesia by means of low-flow rebreathing system
      (fresh gas flow = 1 L/min). All procedures started between 8 and 10 AM, and
      operating room (OR) temperature was maintained between 21 degrees and 23 degrees
      C, with relative humidity ranging between 40% and 45%. For heat retention or
      warming therapy, patients received either low-flow anesthesia only (control, n =
      10), low-flow anesthesia with additional reflective blankets (blanket, n = 10),
      or low-flow anesthesia with active forced-air warming (forced-air, n = 10).
      Tympanic temperature was measured at OR arrival (baseline); immediately following
      general anesthesia induction; 30, 60, 90, and 120 minutes from general anesthesia
      induction; and at the end of surgery. MEASUREMENTS AND MAIN RESULTS: Duration of
      anesthesia, invasiveness of surgery, and baseline core temperature were similar
      in the three groups. Core temperature decreased in all the three groups 30
      minutes after general anesthesia induction compared with baseline (p < 0.01);
      afterwards, it progressively decreased in the control and blankets groups (p =
      0.004), with a reduction from baseline values measured at the end of surgery of
      2.0 degrees C and 1.6 degrees C, respectively. In the forced-air group, after the
      initial significant decrease (p = 0.01 vs. baseline), core temperature
      progressively increased to 35.8 +/- 0.6 degrees C, which was similar to
      preoperative values and significantly higher than either the control or blankets
      groups (p = 0.004). CONCLUSIONS: During combined epidural-general anesthesia for
      elective hip and knee arthroplasty, passive heat retention by means of low-flow
      anesthesia alone and in combination with reflective blankets is ineffective in
      maintaining intraoperative normothermia and definitely inferior to active forced
      air warning.

PMID- 9278837
TI  - Wave recognition and use of the intraoperative unipolar esophageal
      electrocardiogram.
AB  - STUDY OBJECTIVES: To evaluate the automated determination of onset and offset
      times and amplitudes of all the PQRST waves from simultaneously recorded surface
      electrocardiogram (SECG) and unipolar esophageal ECG (EsECG). The occurrence of
      ST segment deviation is also examined. DESIGN: Prospective, observational study.
      SETTING: University hospital. PATIENTS: 30 patients undergoing coronary artery
      bypass graft (CABG) surgery. INTERVENTIONS: SECG and two-lead unipolar EsECG were
      recorded after induction of anesthesia and before cardiopulmonary bypass (CPB).
      MEASUREMENTS AND MAIN RESULTS: The amplitudes of the P and T waves and the ST
      segment deviation were measured. EsECG had more noise than SECG. Slight movement
      of the esophageal electrodes occasionally caused substantial changes in the wave
      amplitudes and ST segment deviation in the unipolar EsECG. The maximum P wave
      amplitude in EsECG was, on average, 97% greater than the maximum P wave amplitude
      in SECG, ST segment deviation in EsECG was observed in the absence of ST segment
      deviation in SECG and vice versa. CONCLUSIONS: The recognition and measurement of
      all the PQRST waves can be improved and automated by simultaneous use of EsECG
      and SECG. The P wave amplitude is greater in EsECG than in SECG, which may
      faciliate the identification of supraventricular versus ventricular arrhythmias.
      ST segment deviation in the unipolar EsECG may not be suitable for the routine
      detection of ischemia.

PMID- 9278838
TI  - Use of esmolol to control bleeding and heart rate during electroconvulsive
      therapy in a patient with an intracranial aneurysm.
AB  - Electroconvulsive therapy (ECT) is a commonly used treatment modality for
      patients with major affective disorders that are unresponsive to pharmacological
      therapy. While ECT has been shown to be a very safe treatment, it is associated
      with transient hemodynamic alterations, including hypertension, which are
      associated with an increased risk of rupture of an intracranial aneurysm. We
      describe our use of the ultrashort acting beta-blocker, esmolol, for blood
      pressure control in a woman with known cerebral aneurysmal disease who required
      ECT for treatment of recurrent major depression.

PMID- 9278839
TI  - Prolonged use of a cook airway exchange catheter obviated the need for
      postoperative tracheostomy in an adult patient.
AB  - Catheters used to facilitate extubations of the known difficult airway are
      usually placed through an existing endotracheal tube (ETT), prior to its removal.
      We present a case in which a #11 Cook airway exchange catheter was placed
      adjacent to the ETT and left intratracheal for an extended period following
      removal of the ETT.

PMID- 9278840
TI  - Bilateral lung collapse in an asthmatic patient during thoracotomy.
AB  - Bilateral sequential pulmonary atelectasis occurred during median sternotomy for
      metastasis resection in a 19-year-old women with asthma. Collapse was secondary
      to mucus plugging and resolved with mechanical ventilation, suctioning, and
      treatment for bronchospasm.

PMID- 9278841
TI  - Cardiac arrest on the day following surgery in children with unrecognized
      rhabdomyolysis.
AB  - We present tow male children who experienced cardiac arrest secondary to
      unrecognized rhabdomyolysis on the day following an uneventful general anesthetic
      and recovery room course for adenotonsillectomy. Neither child exhibited
      hypermetabolism typical of malignant hyperthermia or appeared to have a
      dystrophinophy, prompting the authors to search for other etiologies of childhood
      rhabdomyolysis infrequently associated with anesthesia. In this report, we review
      the heritable metabolic myopathies caused by enzyme deficiencies (enzymopathies)
      that can lead to life-threatening rhabdomyolysis following certain triggering
      conditions, and we offer suggestions for avoiding these triggers in the
      perianesthetic period. We also describe key symptoms an signs that postanesthetic
      caregivers should be aware of, and briefly comment on follow-up diagnostic
      studies.

PMID- 9278842
TI  - Arteriovenous obstruction of arm due to venovenous bypass during liver
      transplantation.
AB  - Two cases of arteriovenous obstruction of the right arm due to venovenous bypass
      during orthotopic liver transplantation are reported. Possible explanation and
      risk factors for the development of this complication are discussed.

PMID- 9278843
TI  - Management of Jehovah's Witness patients for scoliosis surgery: the use of
      platelet and plasmapheresis.
AB  - Four patients whose religious beliefs prohibited accepting blood during surgery
      for scoliosis were anesthetized and managed successfully using plateletpheresis
      and plasmapheresis. Blood losses were replaced with crystalloid and hetastarch
      solutions. In addition, a moderate hypotensive technique was used to minimize
      surgical blood loss. Postoperatively, the patients received iron therapy and/or
      erythropoietin. Three of these patients had an uncomplicated postoperative
      course, however, the fourth patient had some postoperative bleeding with initial
      hemodynamic instability. We believe that patients who refuse to receive blood
      transfusion during surgery because of religious beliefs or health issues can be
      managed safely using other alternatives and techniques such as plateletpheresis
      and plasmapheresis, which conserve and minimize blood loss. Each case should be
      assessed on an individual basis.

PMID- 9278844
TI  - Vitamin K-induced cardiovascular collapse.
AB  - A patient underwent a partial right hepatic lobectomy for adenocarcinoma of the
      colon metastatic to the liver. He was admitted to the surgical intensive care
      unit in stable condition. Six hours after surgery, the patient experienced sudden
      and sever hypotension, bradycardia, and systole. Differential diagnoses included
      acute myocardial infarction, hemorrhage from the surgical site, and pulmonary
      embolism. However, these complications were ruled out. We believe that an
      allergic reaction to vitamin K and its potential side effects are discussed.

PMID- 9278845
TI  - Postoperative oxygen desaturation requiring clinical intervention in premature
      infants receiving spinal anesthesia for inguinal herniorrhaphy.

PMID- 9278846
TI  - Patient safety and scented pediatric anesthesia facemasks.

PMID- 9278847
TI  - The Society for Intravenous Anesthesia: aims and goals.

PMID- 9278848
TI  - Adverse drug interactions in anesthesia.
AB  - Anesthesia often involves the administration of several drugs belonging to
      different classes. In addition, many patients will be taking a number of drugs
      related to their surgical condition or for other medical diseases. Thus, there is
      a considerable potential for drug interactions in the perioperative period, some
      of which may be potentially harmful to patients. The most common interactions
      involve changes in the pharmacokinetics or pharmacodynamics of one drug caused by
      induction or inhibition of the cytochrome P450 enzyme system by another drug.
      Other important interactions involve monoamine oxidase inhibitors, some
      antibiotics, and the tricyclic and tetracyclic antidepressants. These adverse
      interactions are the subject of this review.

PMID- 9278849
TI  - Anesthetic interactions following bolus injections.
AB  - The article presents two main principles of anesthetic interactions: (1) In
      contrast to the interactions of inhalational anesthetics (when deviations from
      additivity are debatable), profound synergistic and antagonistic anesthetic
      interactions between different classes of intravenous drugs are possible due to
      the difference in the mechanism of their action, (2) A combination of intravenous
      anesthetics may provide different outcomes (addition, synergism, or antagonism)
      regarding different components of anesthesia (eg, unconsciousness or movement to
      noxious stimulation) because the components, even if induced by one anesthetic
      drug, have different underlying mechanisms.

PMID- 9278850
TI  - Drug interactions: volatile anesthetics and opioids.
AB  - Multiple drugs are used to provide anesthesia. Volatile anesthetics are commonly
      combined with opioids. Several studies have demonstrated that small doses of
      opioid (i.e., within the analgesic range) result in a marked reduction in minimum
      alveolar concentration (MAC) of the volatile anesthetic that will prevent
      purposeful movement in 50% of patients at skin incision). Further increases in
      opioid dose provide only a further small reduction in MAC. Thus, a ceiling effect
      of the opioid is observed at a MAC value of the volatile anesthetic equal to its
      MAC awake. Recovery from anesthesia when an opioid is combined with a volatile
      anesthetic is dependent on the rate of decrease of both drugs to their respective
      concentrations that are associated with adequate spontaneous ventilation and
      awakening. Through an understanding of the pharmacodynamic interaction of
      volatile anesthetics with opioids and the pharmacokinetic processes responsible
      for the recovery from drug effect, optimal dosing schemes can thus be developed.
      A review of these pharmacodynamic and pharmacokinetic principles that will allow
      clinicians to administer drugs to provide a more optimal anesthetic is provided.

PMID- 9278851
TI  - Pharmacokinetic and pharmacodynamic interactions between opioids and propofol.
AB  - The pharmacokinetic and pharmacodynamic interactions between opioids and propofol
      increasingly have been described and used in clinical practice. It is now known
      that propofol inhibits both alfentanil and sufentanil metabolism, thereby
      increasing the plasma concentrations of these opioids, while alfentanil also
      elevates propofol concentrations. Pharmacodynamically the interaction between
      propofol and the opioids is generally found to be synergistic. From the
      interaction data, the optimal propofol concentrations have been extracted that
      assure adequate anesthesia and the most rapid recovery possible. In the presence
      of fentanyl, sufentanil, and alfentanil, the optimal propofol concentration is
      approximately 3.5 microgram/ml, whereas in the presence of remifentanil, lower
      propofol concentrations of 2.5 to 3 microgram/ml are required.

PMID- 9278852
TI  - Anesthetic drug interaction: an overview.
AB  - Modern anesthetic techniques involve combinations of intravenous (i.v.) and
      inhaled anesthetic drugs that may produce synergistic (supraadditive), additive,
      or antagonistic interactions. Synergistic interaction is most likely to occur
      when two or more drugs produce similar effects by different mechanisms. All of
      the tested combinations of opioids and i.v. sedative-hypnotics have been shown to
      produce synergistic hypnotic effects, and the majority of these interactions are
      predictable and useful in daily practice. Opioids, benzodiazepines, lidocaine,
      and alpha-2 agonists can all reduce the requirements for volatile anesthetics,
      but only the opioids and the alpha-2 agonists produce this effect at clinically
      acceptable concentrations. The usefulness of a drug interaction depends on
      whether it produces greater efficacy or reduced toxicity. Surprisingly, these
      outcomes have only been specifically measured for a handful of common drug
      combinations.

PMID- 9278853
TI  - Fundamentals of feedback control: PID, fuzzy logic, and neural networks.
AB  - Feedback controllers have been shown to bring blood pressure, muscle relaxation,
      inhalation drug concentration, and ventilation to the target level and keep it at
      the target as quickly and as accurately as can a well-trained clinician. Feedback
      control is an effective and convenient clinical tool for optimizing the day-to
      day delivery of anesthetics, reducing induction time, delivering a minimum amount
      of drug, and avoiding costly delays from failing to keep the patient in a desired
      state.

PMID- 9278854
TI  - Neuromuscular blocking drugs: onset and intubation.
AB  - For more than 40 years, succinylcholine has been the traditional choice of muscle
      relaxant to facilitate tracheal intubation, particularly for anesthesia in the
      emergency patient with a full stomach. This presentation reviews factors that
      determine the onset of neuromuscular blockade, particularly with regard to
      tracheal intubation. Measurement of neuromuscular block, both clinical and via
      nerve stimulators, is described and compared, and correlations with intubating
      conditions are attempted. The onset of action of different muscle groups in
      humans is examined in an attempt to explain timing differences leading to the
      more rapid onset of block seen in the laryngeal and ventilatory muscles than in
      the muscles of the hand, which are the usual site of neuromuscular monitoring.
      The onset of different relaxants is compared, and attempts are made to relate the
      differences to neuromuscular pharmacology so as to understand the reasons for the
      rapid onset of succinylcholine (rapid metabolism) and rocuronium (poor potency).
      None of the currently available drugs, or those undergoing clinical
      investigation, possesses the rapid onset and prompt recovery of succinylcholine.
      Despite the formidable side effect profile of succinylcholine, it has not been
      replaced by a nondepolarizing agent for use in emergency conditions. However, the
      alternatives, particularly rocuronium and mivacurium, are drugs with a greater
      safety profile that, in many circumstances, can substitute for succinylcholine.

PMID- 9278855
TI  - The train-of-four count and kinetic-dynamic modelling.
AB  - The intraoperative monitoring of neuromuscular blockade usually involves
      measurement of the muscular responses to motor nerve stimulation. Although
      researchers have the time and technology to obtain predrug control measurements
      of the twitch responses, these are seldom available to the clinician. During
      surgically useful relaxation, there is progressive inhibition of responses to
      train-of-four (TOF) stimulation in the presence of a nondepolarizing relaxant,
      and the clinician can count the number of responses to predict the likely time
      course of paralysis. At the extremes, a count of four (of four) responses may
      indicate a need for further relaxant, whereas with profound paralysis, the
      absence of responses may suggest that reversal with an anticholinesterase may be
      ineffective. Concentrations in the effect compartment associated with these two
      extremes of the TOF count are combined with concentration-time profiles of
      vecuronium with various dose regimens. This study models the effect compartment
      concentrations associated with vecuronium-induced paralysis, combining them
      explicitly with the range of concentrations associated with the TOF count to
      demonstrate the kinetic mechanisms underlying the time-course of paralysis.

PMID- 9278856
TI  - Deletion of the mouse GH-binding protein (mGHBP) mRNA polyadenylation and
      splicing sites does not abolish production of mGHBP.
AB  - In murine species, the GH receptor (mGHR) gene encodes a full-length membrane
      anchored mGHR and a truncated soluble receptor ectodomain (the GH-binding
      protein; mGHBP). The mGHR and mGHBP mRNAs are generated by alternative pre-mRNA
      splicing. Similar GHR/GHBP pairs are generated in other species by proteolysis of
      the GHR. The regulation of GHBP expression and the biological role of GHBP are
      not clear. In order to begin to dissect the factors responsible for regulating
      expression of mGHR and mGHBP, we have cloned a mouse GH receptor/binding protein
      (mGHR/BP) minigene consisting of two mGHR cDNA fragments and an mGHR/BP genomic
      sequence, such that the mGHR and mGHBP can be derived from the minigene by
      mimicking native alternative pre-mRNA splicing. To study the possible role of
      selection of polyadenylation relative to the expression of mGHR and mGHBP, we
      deleted the two tandem poly A addition signals and the flanking AT-rich region
      within the exon (exon 8A) that encodes the carboxy terminus of mGHBP. In
      addition, two other mutated forms of the minigene, one containing a mutated
      alternative splice acceptor site (SAS) near exon 8A and the other possessing a
      deletion of the intron between exons 7 and 8A (intron 7/8A), were generated.
      Expression of the mGHR/BP minigene and its mutated forms in transfected mouse L
      cells revealed that removal of the polyadenylation signals diminished but did not
      abolish either mGHR or mGHBP production. However, mutation of the SAS yielded
      normal mGHR and an mGHBP which may be a result of the translation of an mRNA
      possessing an open reading frame in intron 7/8A. Additionally, removal of intron
      7/8A abolished mGHR expression but resulted in mGHBP production. The results
      suggest that selection of alternative polyadenylation sites of the mGHR/BP gene
      does not play a major role in the regulation of expression of mGHR and mGHBP in
      vitro. These results also suggest that mutation of the SAS near exon 8A does not
      abolish the ability of mGHR/BP gene to produce an mGHBP that retains the ability
      to bind GH, although the new mGHBP may be different from the natural mGHBP at its
      carboxy terminus.

PMID- 9278858
TI  - Glucocorticoids enhance corticotropin receptor mRNA levels in ovine
      adrenocortical cells.
AB  - We have shown previously that chronic treatment with glucocorticoids enhances
      both ACTH-induced cAMP production and ACTH- or 8Br-cAMP-induced steroidogenesis
      of cultured ovine adrenocortical cells. This treatment has been shown to involve
      an increase in the number of ACTH receptors. The present study aimed to explore
      the mechanism of this effect of glucocorticoids on ACTH receptors. Ovine
      adrenocortical cells expressed one major ACTH receptor transcript of 3.6 kb and
      three minor ones of 4.2, 1.8 and 1.3 kb. Dexamethasone treatment of cultured
      cells increased the levels of all these transcripts in a time- and dose-dependent
      manner, with an EC50 of (1.5 +/- 0.6) x 10(-8) M. The mean increase over control
      with 10(-6) M dexamethasone was 144 +/- 11% (n = 14). This enhancing effect was
      specific for glucocorticosteroids. The antiglucocorticoid Ru38486 blocked the
      effect of dexamethasone. Testosterone did not modify, while high concentrations
      of 17 beta-estradiol decreased, ACTH receptor mRNA levels. Treatment of cells
      with aminoglutethimide (an inhibitor of steroidogenesis) resulted in a dose
      dependent decrease in ACTH receptor mRNA levels, which was prevented by
      concomitant treatment with dexamethasone. Treatment with ACTH also increased ACTH
      receptor mRNA levels more than twofold. Addition of aminoglutethimide together
      with ACTH resulted in a smaller increase than that achieved with ACTH alone.
      Neither dexamethasone nor ACTH modified ACTH receptor mRNA half-lives. However,
      these two hormones enhanced the levels of both newly synthesized and total ACTH
      receptor mRNAs. These results indicate that the positive trophic effect of
      glucocorticoids on ovine adrenocortical cells involves an enhancement of the
      transcription rate of the ACTH receptor gene. In addition, they suggest that part
      of the trophic action of ACTH on ACTH receptors may be mediated by ACTH-induced
      steroidogenesis.

PMID- 9278857
TI  - Inhibition of proliferation of prostate cancer cells by a 19-nor-hexafluoride
      vitamin D3 analogue involves the induction of p21waf1, p27kip1 and E-cadherin.
AB  - We have synthesized and studied the ability of a series of seven novel 1
      alpha,25(OH)2 vitamin D3 analogues to inhibit clonal growth of prostate cancer
      cells (LNCaP, PC-3 and DU-145). Addition of double and triple bonds to the C/D
      ring (C-16) and side chain (C-22 and C-23) as well as lengthening of the side
      chain were important for enhanced activity against LNCaP and PC-3. Reorientation
      of the side chain in the 20-epi configuration resulted in analogues that were
      extremely potent only against LNCaP (ED50 approximately 5 x 10(-11) M). Compounds
      with six fluorines on the end of the side chain were very active against both PC
      3 and LNCaP (ED50 approximately 2 x 10(-8) M). DU-145 cells were relatively
      resistant to compounds with all of these modifications, but removal of C-19 (e.g.
      1,25(OH)2-16-ene-23-yne-26,27-F6-19-nor-D3) resulted in an analogue that was
      inhibitory against all three prostate cell lines. Further analysis showed that
      pulse exposure (3 days, 10(-7) M) to this analogue was enough to inhibit clonal
      growth of PC-3 cells by 50%. The same exposure also induced cell cycle arrest of
      all three cell lines, accompanied by upregulated protein expression of the cyclin
      dependent kinase inhibitor (CDKI) known as p21waf1 in all three cell lines, and
      the CDKI known as p27kip1 in LNCaP cells. Associated with upregulation of these
      CDKIs, partial differentiation occurred as measured by increased expression of
      both prostate-specific antigen by LNCaP cells and E-cadherin, a cell adhesion
      protein that may act as a putative tumour suppressor (LNCaP and PC-3 cells). In
      summary, this is the first report of a potent series of 19-nor-vitamin D3
      analogues with the ability to inhibit proliferation of LNCaP, PC-3 and DU-145
      prostate cancer cell lines. These compounds may mediate their potent anti
      proliferative activities through a cell cycle arrest pathway.

PMID- 9278859
TI  - Cloning of cDNA for goldfish activin beta B subunit, and the expression of its
      mRNA in gonadal and non-gonadal tissues.
AB  - We have cloned a full length cDNA coding for activin beta B subunit from the
      goldfish ovary. Sequence analysis of the goldfish activin beta B shows that this
      peptide is extremely conserved across vertebrates. The mature region of goldfish
      activin beta B has 93 and 98% amino acid identity with that of human and
      zebrafish beta B subunit respectively. The identity of the cloned goldfish
      activin beta B was further confirmed by expressing the protein in the Chinese
      hamster ovary (CHO) cells followed by detection of the specific activity of
      activin in the culture medium using F5-5 cell assay. mRNA of goldfish activin
      beta B is expressed in a variety of goldfish tissues including ovary, testis,
      brain, pituitary, kidney and liver, suggesting a wide range of physiological
      roles for activin in the goldfish.

PMID- 9278860
TI  - Cloning and characterization of goldfish activin type IIB receptor.
AB  - We have cloned a full length cDNA coding for the activin type IIB receptor
      (GactRIIB) from the goldfish ovary. GactRIIB shares 73 and 70% amino acid
      identity in the extracellular domain, and 78 and 80% identity in the
      intracellular domain with the type IIB receptors of the mouse and Xenopus
      respectively. The intracellular domain of GactRIIB contains two serine kinase
      consensus sequences, DFKSRN and GTRRYMAPE, in agreement with the reports in other
      vertebrates that serine/threonine phosphorylation is involved in activin signal
      transduction. The identity of GactRIIB was confirmed by transient expression in
      the COS cells followed by activin binding. Iodinated human activin A bound to the
      GactRIIB-transfected cells and the binding could be completely inhibited by
      unlabeled activin. Affinity labeling revealed a band of about 85 kDa, which is in
      agreement with the reported type II receptors in other vertebrates. Together with
      the fact that activin is expressed in the goldfish ovary, the cloning of activin
      receptors from the ovary suggests paracrine and autocrine roles for activin in
      the goldfish ovarian functions.

PMID- 9278861
TI  - IGF, type I IGF receptor and IGF-binding protein mRNA expression in kidney and
      liver of potassium-depleted and normal rats infused with IGF-I.
AB  - Dietary potassium (K) depletion is known to reduce body weight gain and organ
      growth, except for kidney which increases in weight. This renal hypertrophy is
      preceded by increased renal IGF-I levels. In the present study, we investigated
      IGF-I and -II, type I IGF receptor and IGF-binding protein (IGFBP) mRNA
      expression in liver and kidney of K-depleted and normal rats infused with vehicle
      or recombinant human IGF-I. Body weight gain was almost completely arrested in K
      depleted rats without any stimulatory effect of IGF-I infusion. Both absolute and
      relative kidney weight (kidney weight/body weight) were significantly increased
      in K-depleted rats and this was further enhanced by IGF-I infusion. In contrast,
      relative liver weight was comparable in the different groups and unaffected by
      IGF-I infusion. IGF-I mRNA expression was significantly lower in kidney and liver
      of K-depleted animals whereas type I IGF receptor levels were unchanged. In
      contrast, in kidney, K depletion increased IGFBP-1 and -2 mRNA expression with no
      additional effect of IGF-I infusion. In liver of K-depleted animals, IGFBP-1 mRNA
      expression was increased whereas increased IGFBP-1 and -2 mRNA expression was
      observed when these animals were infused with IGF-I. These observations may point
      towards a differential mode of action of the IGFBPs. In kidney increased IGFBP-1
      and -2 mRNA expression may enhance IGF-I bioavailability with subsequent kidney
      growth. In liver, with clearly detectable type I IGF receptor mRNA expression,
      increased IGFBP levels may protect from IGF-I-induced organ growth by decreasing
      IGF-I bioavailability.

PMID- 9278862
TI  - Investigation of the potential role of the germ cell complement in control of the
      expression of transferrin mRNA in the prepubertal and adult rat testis.
AB  - Iron is required for the normal development of germ cells during spermatogenesis.
      Because these cells have no direct access to systemic iron, there exists a
      shuttle system involving production and secretion of the iron-transporting
      protein transferrin by the Sertoli cells. Previous reports using cultures of
      immature Sertoli cells exposed to adult germ cells, or in vivo studies involving
      germ cell depleted adult rat testes, concluded that production of transferrin by
      Sertoli cells is modulated by germ cell complement. In the present study we have
      used in situ hybridisation with cRNA probes directed against the 5' and 3' ends
      of transferrin mRNA to examine the pattern of expression of transferrin in the
      immature and adult rat testis. Adult rats were treated with ethane dimethane
      sulphonate or methoxyacetic acid (MAA) to manipulate their testosterone levels or
      germ cell complement respectively. Initial findings obtained using the 3' probe
      showed a decrease in transferrin mRNA associated with round spermatid depletion.
      However, these data were not confirmed by in situ hybridisation when the 5' probe
      was used. The specificity of the probes was examined using Northern blotting and
      the 3' probe was found to hybridise to the germ cell transcript for hemiferrin
      even under conditions of high stringency. Examination of immature and pubertal
      rat testes by in situ hybridisation using the 5' transferrin-specific probe found
      that as early as 14 days of age the level of expression of transferrin mRNA was
      clearly different between tubules, and the mRNA appeared to be expressed in
      Leydig cells on and after day 31. In the adult rat testis, maximal expression of
      transferrin mRNA was found at stages VIII-XIV, calling into question the
      interpretation of the results of some previous studies showing expression of
      transferrin mRNA at all stages of the spermatogenic cycle. This stage-specific
      pattern of expression was not altered by acute germ cell depletion using MAA.
      However, Northern blot analysis showed a statistically significant increase in
      transferrin mRNA expression at 7 days after MAA treatment when pachytene
      spermatocytes were depleted from tubules at all stages of the spermatogenic cycle
      at which transferrin is normally expressed. In conclusion, we found that
      transferrin mRNA expression was not modulated by round spermatids as has been
      reported previously but that meiotic germ cells may influence expression of
      transferrin at specific stages of the spermatogenic cycle.

PMID- 9278863
TI  - Cloning of mouse islet amyloid polypeptide gene and characterization of its
      promoter.
AB  - Islet amyloid polypeptide (IAPP) was isolated from islet amyloid deposits in
      patients with insulinoma and pancreatic islets of non-insulin-dependent diabetes
      mellitus (NIDDM) and several reports suggested that it may contribute to the
      development of NIDDM. IAPP is mainly expressed and synthesized in pancreatic B
      cells and cosecreted with insulin, so analysis of the transcriptional regulation
      of the IAPP gene would be helpful for the elucidation of pancreatic B cell
      specific gene expression. The mouse IAPP gene spans about 5.8 kb and, like the
      human and rat genes, it consists of three exons, and analysis of the
      promoter/enhancer activity of mouse IAPP gene reveals the region from -171 to -87
      bp to be essential. Within this region, an E-box like sequence, CACCTG (-122 to 
      117 bp), and a TAAT-box like sequence, TTAATG (-139 to -134 bp), are thought to
      be important. The disruption of each sequence resulted in a severe decrease in
      promoter activity, although the decrease was less in the disruption of the E-box
      than that of TAAT-box like sequence, suggesting the latter is more important for
      IAPP gene transcription. Like the rat IAPP gene, the CCAAT-box, which does not
      exist in the human gene, was identified in the mouse gene, indicating the
      possibility of species difference in the IAPP gene transcriptional mechanism. An
      enhancer-like activity was also identified within intron 1, although further
      elucidation is necessary.

PMID- 9278864
TI  - Somatostatin blocks the potentiation of TRH-induced TSH secretion from perifused
      pituitary fragments and the change in intracellular calcium concentrations from
      dispersed pituitary cells elicited by prepro-TRH (PS4) or by tri-iodothyronine.
AB  - TRH and somatostatin (SRIH) are well known to stimulate and to inhibit TSH
      secretion respectively. However, the mechanisms underlying the effect of SRIH on
      thyrotrophs are still not understood. We have previously shown in vitro that the
      TSH response to TRH is potentiated in a Ca(2+)-dependent fashion through the
      activation of dihydropyridine (DHP)-sensitive Ca2+ channels by the prepro-TRH
      (160-169) cryptic peptide (PS4) and tri-iodo-L-thyronine (T3), when the hormone
      was added shortly before a TRH pulse in order to avoid its genomic effect. Using
      perifused rat pituitary fragments, the present study has shown that SRIH
      inhibits, in a dose-dependent manner, the TSH response to physiological
      concentration of TRH (10 nM) and reverses the Ca(2+)-dependent potentiation of
      that response induced either by PS4 or by T3. We have also demonstrated that the
      inhibition by SRIH of the T3 potentiation of TRH-induced TSH secretion is
      pertussis toxin-sensitive. Our data suggest that SRIH inhibits the PS4 and T3
      potentiation of TRH-induced TSH secretion through the inactivation of DHP
      sensitive Ca2+ channels. Using primary cultures of rat anterior pituitary cells
      and videomicroscopy, we have already demonstrated that TRH, as well as PS4 and
      T3, are able to increase intracellular Ca2+ concentration ([Ca2+]i) rapidly, in
      15 s. Our study has shown that SRIH is able to abolish the acute rise in [Ca2+]i
      induced either by PS4 or by T3. Since [Ca2+]i responses to PS4 and T3 are also
      abolished by the DHP nifedipine, our results suggest that [Ca2+]i changes in PS4-
      or T3-sensitive pituitary cells depend directly or indirectly on the activation
      of DHP-sensitive Ca2+ channels and that the inhibitory effect of SRIH may be
      mediated by inactivation of this type of channel.

PMID- 9278865
TI  - Gap junctions as electrical synapses.
AB  - Gap junctions are the morphological substrate of one class of electrical synapse.
      The history of the debate on electrical vs. chemical transmission is instructive.
      One lesson is that Occam's razor sometimes cuts too deep; the nervous system does
      its operations in a number of different ways and a unitarian approach can lead
      one astray. Electrical synapses can do many things that chemical synapses can do,
      and do them just as slowly. More intriguing are the modulatory actions that
      chemical synapses can have on electrical synapses. Voltage dependence provides an
      important window on structure function relations of the connexins, even where the
      dependence may have no physiological role. The new molecular approaches will
      greatly advance our knowledge of where gap junctions occur and permit
      experimental manipulation with high specificity.

PMID- 9278866
TI  - The effect of palytoxin on neuromuscular junctions in the anococcygeus muscle of
      the rat.
AB  - Palytoxin, a highly toxic natural product isolated from zoanthids of the genus
      Palythoa, is accumulated by a wide range of fishes and marine invertebrates used
      as food in the Indo-Pacific. It is responsible for many incidents of human
      morbidity and mortality. The toxin is a potent smooth muscle spasmogen. The cause
      of the contraction of smooth muscle is unclear, but recent work strongly suggests
      that it is primarily initiated by the release of neurotransmitters from the motor
      innervation of the smooth muscle. We show here that palytoxin caused the swelling
      of the muscle cells and some internal organelles of the anococcygeus muscle of
      the rat, but no substantial structural damage to the tissue. Axons and Schwann
      cells were also swollen but the most dramatic feature was the depletion of
      synaptic vesicles from putative release sites in the axons. Some axons were
      physically damaged following exposure to the toxin, but this was relatively
      uncommon (< 10% of all axons studied). In the majority of axons there was no
      damage to nerve terminal membranes, but there was damage to mitochondria. The
      depletion of vesicles involved all types-clear, dense-cored, large and small. Our
      observations and pharmacological data gathered elsewhere, provide a
      neuropathological basis for the spasmogenic activity of palytoxin.

PMID- 9278867
TI  - Ultrastructure and blood-nerve barrier of chordotonal organs in the Drosophila
      embryo.
AB  - Chordotonal organs of Drosophila embryos have become models for studies of
      developmental biology and molecular genetics due to their consistent segmental
      placement and mutability. Our first goal was to find the origin and anatomical
      correlate of the blood-nerve barrier of this PNS proprioreceptor in wild type
      embryos. The concept of a blood-nerve barrier for the PNS of the Drosophila
      embryo is new, and the present data are the first in this regard. A second goal
      was to reveal the ultrastructure of these four-celled stretch receptors, focusing
      particularly on the 'core' of this organ: the bipolar neuron enclosed by a
      scolopale cell. These latter data have resulted in a graphic reconstruction of
      the chordotonal organ which reveals how the four consistent cells fit together.
      At Stage 13 we first observed a clearly recognizable scolopale cell with an
      enclosed neuron. Surprisingly, an operative blood-nerve barrier, comprised of
      occlusive pleated-sheet septate junctions, exists at this relatively early stage.
      A blood-brain barrier is not yet functioning in the CNS during this same stage,
      as the perineurium is not present until Stage 17. Cross-sectional views of a more
      mature chordotonal organ show that the neuron's inner segment has a 'tongue-in
      groove' formation which fits the dendrite into the scolopale cell. Other newly
      discovered fine structural features are: hemidesmosomes linking individual
      scolopale rod bundles to the inner dendrite, and a cap cell matrix bonding with
      the tip of the ciliary dendrite. Functional aspects of these findings are
      discussed.

PMID- 9278868
TI  - Structural-functional differences of a crab motoneuron to four stomach muscles.
AB  - A motor unit in the stomach of the blue crab, Callinectes sapidus, consists of
      four separate muscles involved in different aspects of the trituration and
      filtering of food. Motor nerve terminals to two of the muscles (CPV7a and GM5)
      release small amounts of transmitter (low-output) while those to the other two
      muscles (CV2 and CV3) release between three and five-fold greater amounts (high
      output). Structural features underlying the disparity in synaptic strength were
      analysed with thin serial-section electron microscopy. Nerve terminals were
      similar in their volume percent of mitochondria, clear vesicles and dense core
      vesicles among the four muscles. This was also the case for the number and size
      of synaptic contacts. However, presynaptic dense bars representing active zones
      were longer and occurred more frequently at high-output synapses than at low
      output ones. High-output synapses were also characterized by the close spacing of
      adjacent dense bars. The longer and more closely spaced dense bars at high-output
      synapses would be factors in the generation of larger synaptic potentials in
      these terminals compared to their low-output counterparts. Other factors,
      however, need to be considered to fully account for the physiological differences
      in synaptic strength among the four muscles.

PMID- 9278869
TI  - Characterization of a new neurosecretory cell type containing gastrin
      cholecystokinin-like peptide in the locust pars intercerebralis: ultrastructural
      and immunocytochemical studies, in situ and in vitro.
AB  - A new neurosecretory cell type of the locust pars intercerebralis, immunolabelled
      with an antiserum against a vertebrate peptide related to gastrin-cholecystokinin
      (CCK-8(s)), was characterized both in situ and in primary cell cultures. Semithin
      sections of pars intercerebralis were first immunostained in order to identify
      neurosecretory cells containing CCK-like material and then examined by electron
      microscopy. The neurosecretory cells containing CCK-like material were
      paraldehyde fuchsin negative and were unequivocally identified in ultrathin
      sections adjacent to immunostained semithin sections. They exhibited
      neurosecretory vesicles of variable electron density, ranging in diameter from
      150 to 250 nm. Immunogold labelled ultrathin sections adjacent to unlabelled
      ultrathin sections allowed for the unambiguous localization of CCK-like
      immunoreactive material over the neurosecretory vesicles of the cells containing
      CCK-like material. Immunoreactivity towards CCK-8(s)-like peptide could also be
      detected in pars intercerebralis neurosecretory neurons grown in vitro. The CCK
      like positive neurons showed a multipolar morphology with fine processes
      radiating from the cell body. The positive cells had the same ultrastructural
      characteristics as the in situ CCK-like neurons. The pattern of neurite outgrowth
      on reactive CCK-like neurosecretory cells in vitro and the neuroanatomical
      pathway of the CCK-like immunoreactive neurosecretory cells in situ could be
      correlated. On the basis of their number, size and localization in the locust
      pars intercerebralis, it is possible that the CCK-like neurosecretory cells
      correspond to neurosecretory cell type C, which has not, to date, been identified
      at the ultrastructural level.

PMID- 9278870
TI  - Effects of neurotrophic factors and cell substrates on the differentiation of a
      sympathoadrenal progenitor cell line.
AB  - The detailed spatial organization of cytoskeletal proteins in an immortalized
      sympathoadrenal precursor cell line, termed MAH, was studied when the cells were
      grown on cellular substrates and when treated with combinations of recombinant
      nerve growth factor, ciliary neurotrophic factor and basic fibroblast growth
      factor. In response to growth factors, MAH cells expressed appropriate
      distributions of phosphorylated and non-phosphorylated neurofilaments, and
      dendrite and axon specific microtubule associated proteins. Sequential stages of
      maturation and axon formation were identified as the MAH cells established
      neuronal polarity and developed into sympathetic-like neurons. Combinations of
      the growth factors initiated growth associated protein-43 expression in processes
      and promoted the MAH cells to acquire sympathetic-like neuron characteristics
      with long, thin processes that branched and often terminated in elaborate growth
      cones. When treated with the three trophic factors, 15% of the MAH cells
      differentiated into sympathetic-like neurons, in contrast to less than 10% when
      cultured with ciliary neurotrophic factor plus nerve growth factor. An enhanced
      cholinergic phenotype was evident in the MAH cells when grown with ciliary
      neurotrophic factor. MAH cells also expressed neuron-specific markers when co
      cultured on enriched substrates of smooth muscle, fibroblasts or Schwann cells.
      The results indicate that this sympathoadrenal cell lineage, carrying the v-myc
      oncogene, can express appropriate cytoskeletal markers in the process of neuronal
      differentiation when induced by neurotrophic factors or by specific cellular
      conditions in vitro.

PMID- 9278871
TI  - Structural alterations of the hippocampal formation of adrenalectomized rats: an
      unbiased stereological study.
AB  - Previous studies have demonstrated that adrenalectomy rapidly induces cell death
      in hippocampal formation. However, these previous studies have involved only
      qualitative observations or biased estimates. Therefore, the selectivity of the
      effects of adrenalectomy and the magnitude of changes occurring, remain
      controversial. The present work employed unbiased stereological tools to examine
      the effects of adrenalectomy on the number of neurons in, and the volume of, the
      hippocampal formation. Male rats were adrenalectomized 15, 30 or 120 days before
      sacrifice at 180 days of age. The total number of neurons in the somal layers and
      hilus of the hippocampal formation was estimated using the optical fractionator.
      The volume of the different layers of each subdivision in the hippocampal
      formation was determined according to the Cavalieri principle. A progressive
      reduction, reaching 43%, was found in the total number of granule cells.
      Adrenalectomized animals exhibited a reduction in the volume of all layers of the
      dentate gyrus. No other region of the hippocampal formation displayed significant
      cell loss or a reduction in volume. In addition, the main neuronal subpopulations
      of the dentate gyrus were also evaluated, and a reduction in the total number of
      GABA- and neuropeptide Y-immunoreactive neurons in the molecular and granule cell
      layers of adrenalectomized rats was found. No quantitative changes were observed
      in the hilus. To characterize the glial response to the neuronal degeneration, we
      estimated the total number of cells immunoreactive for glial fibrillary acidic
      protein in the dentate gyrus. Although no variation in the total number of glial
      cells was found, signs of astroglial activation were observed in the
      adrenalectomized group. The present data strengthen the evidence pointing to the
      critical role of corticosteroids in maintaining the structural integrity of
      dentate gyrus.

PMID- 9278872
TI  - Left bundle branch block and coronary artery disease: accuracy of dipyridamole
      thallium-201 single-photon emission computed tomography in patients with exercise
      anteroseptal perfusion defects.
AB  - BACKGROUND: Reduced septal or anteroseptal uptake of thallium-201 during exercise
      is frequently observed in patients with left bundle branch block (LBBB) even in
      the absence of left anterior descending (LAD) coronary artery disease. The
      purpose of this study was to evaluate prospectively the accuracy of dipyridamole
      201Tl single-photon emission computed tomography (SPECT) in detecting LAD
      coronary artery disease in patients with LBBB and septal or anteroseptal
      perfusion defects on exercise 201Tl SPECT. METHODS AND RESULTS: Twelve
      consecutive patients (10 men and two women) with complete LBBB and septal or
      anteroseptal perfusion defects on exercise 201Tl SPECT underwent dipyridamole
      201Tl SPECT. The delay between dipyridamole and exercise was 2 to 30 days.
      Coronary angiography was performed during this period in all patients. Six (50%)
      of 12 patients with exercise perfusion defects showed normal perfusion after
      dipyridamole; all had normal coronary angiograms. The remaining six patients also
      had positive results of dipyridamole studies, two with moderate and four with
      severe septal or anteroseptal perfusion defects. Coronary angiography showed
      significant (> 50%) LAD coronary artery stenosis in three patients; three
      patients with severe septal or anteroseptal perfusion defects after dipyridamole
      had normal coronary angiograms. Neither the evaluation of apical involvement nor
      the presence of dilated ventricles, decreased left ventricular ejection fraction,
      or wall motion abnormalities could help to identify (or explain) false-positive
      results. CONCLUSION: This study confirms that dipyridamole is more accurate than
      exercise in excluding LAD coronary artery disease. However, there are still false
      positive results and the severity of the septal or anteroseptal perfusion defect
      does not add additional information to identify LAD coronary artery disease.
      Coronary angiography is thus necessary for positive dipyridamole study results to
      identify coronary artery disease as a major prognostic factor in patients with
      LBBB.

PMID- 9278873
TI  - Differentiation of myocardial ischemia and necrosis by technetium 99m glucaric
      acid kinetics.
AB  - BACKGROUND: Current clinical approaches may not always be helpful in the early
      differentiation of necrotic tissue from ischemic viable myocardium in patients
      with acute myocardial infarction. Tc-99m-glucaric acid is a carbohydrate ligand
      that may permit differentiation of necrosis from ischemia. However, the
      myocardial kinetics of Tc-99m-glucaric acid have not been well defined early
      after myocardial injury. The aim of this study was to evaluate the effect of
      necrosis in comparison to postischemic injury alone on the kinetics of Tc-99m
      glucaric acid with the use of an isolated perfused rat heart model. METHODS AND
      RESULTS: Three groups of hearts were studied: group I: control (n = 6); group II:
      postischemia (15 minutes of no flow with complete reperfusion, n = 6); and group
      III: necrosis (90 minutes of no flow to induce necrosis with complete
      reperfusion, n = 6). Tc-99m-glucaric acid (1.3 +/- 0.6 mCi/L of buffer) was
      perfused for 30 minutes to evaluate tracer accumulation. Then tracer-free buffer
      was perfused for 45 minutes to evaluate clearance. The peak accumulation relative
      to the control group mean was significantly increased (p < 0.01) in group III
      (necrosis) (254% +/- 75%) compared with control (100% +/- 10%) and compared with
      postischemia (108% +/- 26%). On kinetic data analysis, the monoexponential
      clearance rate constant: (kc) was significantly reduced with necrosis (control:
      kc = 20.2 +/- 14.0 x 10(-4) sec-1; postischemia: kc = 22.3 +/- 15.2 x 10(-4) sec
      1; and necrosis: kc = 1.2 +/- 0.3 x 10(-4) sec-1; p < 0.05). A retention fraction
      was calculated from the activity after 45 minutes of clearance corrected for the
      peak activity for each group. The necrotic group had significant myocardial
      retention in comparison to control and postischemia (control: 12% +/- 8%;
      postischemia: 14% +/- 16%; necrosis: 64% +/- 10%; p < 0.01). CONCLUSIONS: The
      accumulation and retention of Tc-99m-glucaric acid is markedly increased in the
      presence of myocardial necrosis in comparison to control and postischemic
      myocardial injury. In this model, Tc-99m-glucaric acid is capable of defining the
      presence of necrotic myocardial injury in comparison to postischemic injury
      alone. This agent may have potential application for the early differentiation of
      ischemic from necrotic myocardium in acute myocardial infarction.

PMID- 9278874
TI  - Avidity of technetium 99m glucarate for the necrotic myocardium: in vivo and in
      vitro assessment.
AB  - BACKGROUND: Similar to other 99mTc-based infarct-avid agents, 99mTc-glucarate
      localizes in myocardial infarcts. Whether severely ischemic viable myocytes
      sequester 99mTc-glucarate is uncertain. To assess the infarct specificity, in
      vitro and in vivo studies were performed. METHODS AND RESULTS: H9C2 embryonic rat
      cardiocytes cultured under normoxia (N) or hypoxia (H) for 24 hours in 7.5 muCi
      99mTc-glucarate were compared with necrotic cardiocytes. Mean H/N ratio (3.0 +/-
      0.004, mean +/- SD) was significantly less than that of the necrotic/N ratio
      (39.9 +/- 6.5, p < 0.01). Reperfused myocardial infarction (MI) in 4 dogs
      confirmed by 201Tl (0.5 to 1.0 mCi) scintigraphy were imaged serially with
      simultaneously injected mixture of 99mTc-glucarate and 111In-antimyosin Fab.
      Infarcts were detected scintigraphically within 4 to 10 minutes with 99mTc
      glucarate. 111In-antimyosin required more than 1 hour. Myocardial distribution at
      5 hours showed a direct correlation between 99mTc-glucarate and 111In-antimyosin
      uptake (r = 0.99, p < 0.0001). Both 99mTc-glucarate (r = -0.777, p < 0.0001) and
      111In-antimyosin (r = -0.775, p < 0.0001) were inversely related to 201Tl
      distribution. CONCLUSIONS: The near perfect correlation between 99mTc-glucarate
      and 111In-antimyosin uptake (r = 0.99) in reperfused canine MI and the
      insignificant glucarate uptake by viable cardiocytes in vitro attest to the
      avidity of 99mTc-glucarate for the necrotic myocardium and favor its use as a
      specific early marker of myocyte necrosis in acute MI.

PMID- 9278875
TI  - Improved diagnostic accuracy of planar imaging with technetium 99m-labeled
      tetrofosmin compared with thallium-201 for the detection of coronary artery
      disease.
AB  - BACKGROUND: Receiver operating characteristic (ROC) curve analysis provides
      detailed information about the performance of a diagnostic test. METHODS AND
      RESULTS: As part of a multicenter phase III trial, 160 patients with known or
      suspected coronary artery disease underwent planar stress-rest 99mTc-labeled
      tetrofosmin and stress-redistribution 201Tl imaging within 14 days of each other,
      to compare the diagnostic accuracy of these imaging modalities by ROC curve
      analysis. Coronary arteriography was used as the reference standard and greater
      than 70% stenosis was considered significant. ROC curve analysis showed improved
      detection of coronary artery disease with 99mTc-labeled tetrofosmin compared with
      201Tl, with ROC curve areas of 0.765 versus 0.644, respectively (p = 0.02). 99mTc
      labeled tetrofosmin also better identified single-vessel disease in those without
      previous myocardial infarction (ROC curve areas of 0.684 vs 0.510 for 99mTc
      labeled tetrofosmin and 201Tl, respectively; p = 0.04) and enhanced the detection
      of multivessel disease in those with previous myocardial infarction (ROC curve
      areas of 0.764 vs 0.638, respectively; p = 0.02). CONCLUSIONS: Detailed
      assessment of diagnostic performance by ROC curve analysis shows that, for planar
      imaging, 99mTc-labeled tetrofosmin enhances the detection of coronary artery
      disease compared with 201Tl.

PMID- 9278876
TI  - Cardiac stress-rest single-photon emission computed tomography with technetium
      99m-labeled tetrofosmin: influence of washout kinetics on regional myocardial
      uptake values of the rest study with a 1-day protocol.
AB  - BACKGROUND: The purpose of this study was to evaluate (1) the washout kinetics of
      99mTc-labeled tetrofosmin, separately for myocardium with normal and reduced
      perfusion, and (2) its influence on quantitative analysis in a 1-day stress-rest
      protocol. METHODS AND RESULTS: Twenty-five patients with angiographically proved
      coronary artery disease underwent bicycle exercise stress testing with injection
      of 200 MBq 99mTc-labeled tetrofosmin and first single-photon emission computed
      tomographic (SPECT) imaging 40 minutes after injection. A second SPECT was
      acquired 2.3 +/- 0.4 hours after the first one immediately before rest injection
      of 800 MBq 99mTc-labeled tetrofosmin. The rest (third) SPECT was acquired 15
      minutes thereafter. The relative washout fraction per time (WOFt) was calculated
      assuming linear washout kinetics. Thirty-three regional uptake values per study
      were calculated, normalized to the perfusion maximum (100%) in either the
      postexercise SPECT and the rest SPECT, for the latter with and without correction
      of remaining counts from stress injection. In regions with normal perfusion, WOFt
      was 11.5% +/- 3.5% per hour. In regions with markedly reduced perfusion (relative
      uptake < 50%, WOFt was 8.3% +/- 9.9% per hour. The highest variation of the
      relative uptake values between rest SPECT with and without correction of
      remaining counts from stress injection was 5.4% +/- 3.5% in regions with stress
      induced ischemia. CONCLUSION: To use a 1-day protocol with a stress-rest
      radioactivity ratio of 1:4 and an interval of more than 2 hours between the
      examinations, a correction for remaining counts from stress injection seems not
      to be necessary for the quantitative analysis of rest SPECT.

PMID- 9278878
TI  - Who is interpreting nuclear cardiology studies in the United States, and what are
      the requirements for privileges? A national survey of institutional policies from
      80 major medical centers.
AB  - BACKGROUND: This survey was conducted to determine the guidelines used by major
      medical centers in the United States for obtaining hospital privileges to
      interpret nuclear cardiology studies. The American College of Cardiology (ACC)
      and the American Society of Nuclear Cardiology (ASNC) have established guidelines
      to help maintain an adequate level of proficiency in the practice of nuclear
      cardiology. These guidelines were published only recently, and many hospitals
      have adopted different processes to obtain these privileges. It is likely that a
      marked difference among institutions exists. METHODS AND RESULTS: The survey was
      conducted predominantly by mailings with additional telephone communications if
      more information was needed. Chiefs of cardiovascular medicine sections were
      contacted to provide information concerning the policy of granting nuclear
      cardiology privileges at his or her institution. The responses were tabulated in
      four categories and the responders were asked to comment on whether they agreed
      or disagreed with their own university's policy. Of 80 responses (68%) from 121
      institutions, cardiologists were involved in reading these studies in 62 (78%)
      and radiologists were the sole interpreters in 18 (22%). ACC or ASNC guidelines
      were strictly followed at 48 sites (60%). Eight (10%) and 6 (8%) of these
      institutions mandated a minimum requirement of, respectively, 12 and 6 months of
      additional training in nuclear cardiology. Ten (13%) of the cardiologists
      surveyed disagreed with their own institution's policies, primarily noting that
      the ACC and ASNC guidelines were more appropriate. CONCLUSION: The recently
      established ACC/ASNC guidelines clearly have had an impact on the practice of
      attaining privileges in nuclear cardiology and are the most commonly quoted
      criteria used by institutions in the United States to assess competence in
      nuclear cardiology.

PMID- 9278877
TI  - F18-fluorodeoxyglucose single-photon emission computed tomography predicts
      functional outcome of dyssynergic myocardium after surgical revascularization.
AB  - BACKGROUND: Prediction of functional recovery after revascularization is possible
      with positron emission tomography and F18-fluorodeoxyglucose (FDG). Recently, the
      use of FDG in combination with single-photon emission computed tomography
      (SPECT), with 511 keV collimators, has been proposed to allow more widespread use
      of FDG. In the current study we aimed to predict improvement of regional left
      ventricular function after surgical revascularization with FDG and SPECT. METHODS
      AND RESULTS: Twenty-seven patients with regional wall motion abnormalities (on
      echocardiography) underwent early thallium-201 (Tl-201) SPECT to assess perfusion
      and FDG SPECT to assess regional glucose uptake. The left ventricular myocardium
      was divided into 13 segments. For each segment, tracer uptake was evaluated
      visually (with the use of a 4-point scoring system) by consensus of two
      observers. Myocardial viability was determined in dyssynergic segments on
      echocardiography and defined as normal perfusion or increased FDG uptake in a
      perfusion defect (mismatch). Absence of viability was defined as a perfusion
      defect without increased FDG uptake (match). Improvement of regional wall motion
      was assessed 3 months after revascularization. In the group of segments that were
      viable on FDG/Tl-201 SPECT (n = 64), the segmental wall motion score decreased
      from 1.4 +/- 0.5 to 0.6 +/- 0.7 (p < 0.01), whereas the segmental wall motion
      score remained unchanged in nonviable segments (n = 72): 1.6 +/- 0.5 versus 1.5
      +/- 0.6 (not significant). Forty-six (72%) of the 64 segments that were viable on
      FDG/Tl-201 SPECT demonstrated improved contractile function after coronary
      revascularization. In contrast, only 7 (10%) of 72 nonviable segments on FDG/Tl
      201 SPECT showed improvement in function after revascularization (p < 0.01 versus
      viable segments). The sensitivity, specificity, and positive and negative
      predictive values were 87%, 78%, 72%, and 90%, respectively. CONCLUSION: This
      study shows that FDG/Tl-201 SPECT can identify patients who improve in regional
      ventricular function after revascularization.

PMID- 9278879
TI  - Advantages and limitations of experimental techniques used to measure cardiac
      energy metabolism.
AB  - The heart requires a constant supply of energy to sustain contractile function,
      which is supplied by hydrolysis of adenosine triphosphate derived primarily from
      the metabolism of fatty acids and carbohydrates. Understanding how production of
      adenosine triphosphate is regulated in the heart is critical to an understanding
      of how alterations in energy metabolism contribute to the severity of cardiac
      disease. A number of techniques can be used to measure energy metabolism in the
      heart. They include biochemical measurement of metabolites and enzymes of
      intermediary metabolism, measurement of arteriovenous differences in carbon
      substrate extraction by the heart, measurement of high-energy phosphates with 31P
      nuclear magnetic resonance, measurement of the rate of flux through the pathways
      of intermediary metabolism with 14C- and 3H-labeled carbon substrates,
      measurement of tricarboxylic acid cycle activity with 13C nuclear magnetic
      resonance, and measurement of glucose uptake and oxidative metabolism with
      positron emission tomography. Each of these techniques has advantages and
      limitations.

PMID- 9278882
TI  - Surgical treatment of anomalous origin of the left coronary artery from the
      pulmonary artery: late results evaluated with dobutamine stress gated single
      photon emission computed tomography sestamibi study.

PMID- 9278880
TI  - Detection of coronary artery disease in women with use of stress single-photon
      emission computed tomography myocardial perfusion imaging.

PMID- 9278881
TI  - Technetium 99m glucarate: what will be its clinical role?
AB  - With publication of the studies by Khaw et al. and Beanlands et al. in this issue
      of the Journal, there is mounting evidence that 99mTc glucarate is taken up by
      infarcted but not by ischemic myocardium. The early myocardial distribution and
      rapid blood-pool clearance of 99mTc glucarate suggest important diagnostic
      potential in the very early detection of acute myocardial infarction and for the
      identification of successful acute revascularization therapy. To understand the
      full diagnostic implications of 99mTc glucarate accumulation in the myocardium,
      larger human trials are now needed. It will be critically important to document
      the capabilities of 99mTc glucarate to identify, early on, acute myocardial
      infarction in the presence of a persistently occluded infarct-related coronary
      artery in human beings.

PMID- 9278883
TI  - Determination of enantiomeric composition of ibuprofen in bulk drug by proton
      nuclear magnetic resonance spectroscopy with a chiral lanthanide chelate.
AB  - The enantiomeric composition of ibuprofen was determined in a simple and reliable
      manner by proton nuclear magnetic resonance spectroscopy with a chiral lanthanide
      chelate. Optimum complexation with the europium (III) chelate took place in CCl4
      after conversion of the enantiomeric sample into a mixture of methyl esters. The
      optimization of the experimental conditions in terms of substrate concentration
      and lanthanide chelate to substrate molar ratio led to two sets of signals of
      utility for quantitative purposes. Analysis of synthetic enantiomeric mixtures by
      the proposed method demonstrated excellent agreement between the assay results
      and the known masses of each enantiomer present in the mixture samples. The
      average +/- S.D. recovery values were 99.39 +/- 0.92 and 99.42 +/- 0.68% (n = 10)
      of (S)-(+)-ibuprofen depending on whether the quantitation was based on the alpha
      methyl protons or ester methyl protons, respectively.

PMID- 9278884
TI  - Solid-state investigation of fluocinolone acetonide.
AB  - Three crystalline modifications of fluocinolone acetonide, A, B and C, were
      characterized by means of FTIR, DSC, TG-FTIR, MICRO-FTIR and X-ray
      diffractometry. They were easily differentiated by their IR absorption bands in
      the 3600-3400 cm-1 range. The thermal behavior was also elucidated using combined
      techniques; thermomicroscopy and thermogravimetry coupled with Fourier transform
      infrared spectroscopy were found to be very useful tools for a better
      understanding of thermal events. On heating, form A and C were fully converted
      into form B. Polymorph A was found to be enantiotropically related to B, while
      form C was monotropically related to B. The existence of three polymorphs was
      confirmed by means of their different X-ray diffraction patterns. Detailed
      methods of preparation of the three modifications are also described.

PMID- 9278885
TI  - Flow-injection biamperometric determination of epinephrine.
AB  - A flow-injection manifold is proposed for the determination of epinephrine. The
      experimental procedure is based on the indirect biamperometric detection of the
      drug by using Fe(III)-Fe(II) as an indicating redox system and a flow-through
      detector with two polarized Pt wire electrodes. The calibration graph is linear
      over the range 0.3-20 micrograms ml-1 of epinephrine. The relative standard
      deviation for the determination of 10 micrograms ml-1 of epinephrine is 1.5% (n =
      25) and the sample throughput is 153 h-1. The method was applied to the
      determination of epinephrine in two commercially available pharmaceutical
      preparations.

PMID- 9278886
TI  - Potentiometric flow injection determination of serum bromide in patients with
      epilepsy.
AB  - A flow injection system was constructed using a bromide-selective electrode and
      used to determine serum bromide in patients with epilepsy. A 10-microliter serum
      sample was injected into a carrier stream flowing at 0.12 ml min-1. Potential
      changes and bromide concentrations were linearly related in the range 3-50 mM.
      The lower limit of detection for serum bromide was 1 mM and this electrode
      sensitivity spanned the entire concentration range required for bromide therapy
      (9-24 mM). The results compared favourably with those obtained by colorimetry.

PMID- 9278887
TI  - Study on the fluorescence system of chlortetracycline-Eu-TOPO-sodium dodecyl
      sulfonate and the determination of chlortetracycline.
AB  - The fluorescence system of Eu-chlortetracycline-TOPO-sodium dedecyl sulfonate was
      studied. It was found that chloretetracycline formed a complex with Eu(III) at pH
      8.0-9.0 and then emitted the characteristic fluorescence of Eu(III). TOPO and
      sodium dodecyl sulfonate greatly enhanced the fluorescence intensity of the
      system. The experiments indicated that under the optimum determining conditions a
      linear relationship was obtained between the fluorescence intensity and
      chlortetracycline concentration in the range of 2.0 x 10(-8)-1.0 x 10(-5) M. The
      detection limit was 6.0 x 10(-9) M. In addition, the luminescence mechanism of
      the complex system has been discussed.

PMID- 9278888
TI  - Application of terbium sensitized fluorescence for the determination of
      fluoroquinolone antibiotics pefloxacin, ciprofloxacin and norfloxacin in serum.
AB  - A simple, rapid and sensitive spectrofluorimetric method for the determination of
      fluoroquinolone antibiotics, norfloxacin (NOR), ciprofloxacin (CIP) and
      pefloxacin (PEF) is described. The method is based on the radiative energy
      transfer from fluoroquinolones to terbium ions (Tb3+) in the presence of tri-n
      octylphosphine oxide (TOPO) in weakly acidic (pH 5.5) micellar solution of
      cetylpyridinium chloride (CPCI). Optimum conditions for the formation of the
      fluoroquinolone-Tb(3+)-TOPO ternary complexes have been investigated. Under
      optimized conditions the detection limits are 1.7, 1.2 and 4.4 nM for NOR, CIP
      and PEF, respectively, while the range of application for all three drugs is 0.05
      10 microM. The method has been successfully applied to the determination of NOR,
      CIP and PEF in serum samples after deproteinization with acetonitrile (serum
      acetonitrile; 1:2, v/v). The mean recoveries from serum samples spiked with NOR,
      CIP and PEF (5.0-50.0 microM) were (90.3 +/- 4.9), (105.0 +/- 3.6), and (95.3 +/-
      1.5)% respectively. Within-run and day-to-day s, values for 5.0, 25.0 and 50.0
      microM of each fluoroquinolone varied from 1.7 to 5.4% and from 3.3 to 12.8%,
      respectively. The influence of several usually coadministered drugs on the
      determination of fluoroquinolones in serum has been investigated.

PMID- 9278889
TI  - Physicochemical properties of enrofloxacin.
AB  - The physicochemical properties of enrofloxacin, a fluoroquinolone that inhibits
      the activity of bacterial DNA gyrase, are described. Its spectral, solubility and
      related physicochemical characteristics are discussed. The dissociation behaviour
      of enrofloxacin was examined by UV spectrophotometry at 25 degrees C in a series
      of buffers ranging from pH 1 to 10. The corresponding macro- and microscopic
      dissociation constants were calculated. The apparent n-octanol-water partition
      coefficients were measured from pH 2 to 10.

PMID- 9278890
TI  - Pharmacokinetic and pharmacodynamic study of imidaprilat, an active metabolite of
      imidapril, a new angiotensin-converting enzyme inhibitor, in spontaneously
      hypertensive rats.
AB  - The pharmacokinetics and pharmacodynamics (PK/PD) of imidaprilat, an active
      metabolite of imidapril, a new angiotensin-converting enzyme (ACE) inhibitor,
      were investigated. Imidapril was infused subcutaneously for 4 weeks via an
      osmotic pump implanted under the skin in the back of male spontaneously
      hypertensive rats (SHRs). Plasma concentration of imidaprilat, systolic blood
      pressure (SBP), and plasma ACE activity were determined periodically. The plasma
      concentration of imidaprilat increased in proportion to the infusion rates and
      was maintained for 4 weeks. The SBP and ACE activity did not decrease in
      proportion to the infusion rates due to the saturation of the pharmacologic
      effects, but these actions also were maintained for 4 weeks. The PK/PD of
      imidaprilat were not influenced by aging of SHRs. The antihypertensive action in
      subcutaneous infusion of imidapril was as potent as that in oral administration
      at the same dose, although the maximum plasma concentration of imidaprilat in
      subcutaneous infusion was one-eightieth times of that in oral administration. The
      action was also maintained 28 times longer than that in oral administration,
      indicating that subcutaneous infusion is useful as an administration route.
      Furthermore, good correlation between plasma imidaprilat concentration and SBP
      was observed in subcutaneous infusion, indicating that plasma concentration may
      be a useful marker of pharmacologic action.

PMID- 9278891
TI  - Pharmacokinetics and pharmacodynamics of a sustained-release biodegradable pellet
      containing imidapril, a new angiotensin-converting enzyme inhibitor in
      spontaneously hypertensive rats.
AB  - The pharmacokinetics and pharmacodynamics (PK/PD) of a sustained-release
      biodegradable pellet containing imidapril, a new angiotensin-converting enzyme
      (ACE) inhibitor, were investigated in comparison with those of an osmotic pump in
      male spontaneously hypertensive rats (SHRs). A pellet was prepared from copolymer
      of DL-lactic acid and glycolic acid by the melt-pressing technique. Imidapril was
      released in vitro from the pellet at an approximately zero-order rate and the
      release profile was similar to that of the osmotic pump. Imidapril was
      administered subcutaneously via a pellet or an osmotic pump implanted under the
      skin in the back of SHRs. Plasma concentrations of imidaprilat as an active
      metabolite of imidapril, plasma ACE activity and systolic blood pressure (SBP)
      were determined periodically. The plasma concentration of imidaprilat during the
      administration of a pellet was maintained for 4 weeks, and the plasma
      concentration profile was close to that of the osmotic pump. Both groups of
      pellet and osmotic pump significantly inhibited plasma ACE activity and reduced
      SBP for 4 weeks, and these action profiles were similar in both groups. In
      addition, in vivo release profile of the pellet was close to the in vitro release
      profile, and the in vivo release profiles of the pellet and the osmotic pump were
      similar to each other. From these results, it was found that the PK/PD of a
      biodegradable pellet were close to those of the osmotic pump, and it was shown
      that the pellet may be a useful system to maintain the plasma concentration of
      imidaprilat for a long time.

PMID- 9278892
TI  - Stability of curcumin in buffer solutions and characterization of its degradation
      products.
AB  - The degradation kinetics of curcumin under various pH conditions and the
      stability of curcumin in physiological matrices were investigated. When curcumin
      was incubated in 0.1 M phosphate buffer and serum-free medium, pH 7.2 at 37
      degrees C, about 90% decomposed within 30 min. A series of pH conditions ranging
      from 3 to 10 were tested and the result showed that decomposition was pH
      dependent and occurred faster at neutral-basic conditions. It is more stable in
      cell culture medium containing 10% fetal calf serum and in human blood; less than
      20% of curcumin decomposed within 1 h, and after incubation for 8 h, about 50% of
      curcumin is still remained. Trans-6-(4'-hydroxy-3'-methoxyphenyl)-2,4-dioxo-5
      hexenal was predicted as major degradation product and vanillin, ferulic acid,
      feruloyl methane were identified as minor degradation products. The amount of
      vanillin increased with incubation time.

PMID- 9278894
TI  - Development and validation of a dissolution method for warfarin sodium and
      aspirin combination tablets.
AB  - A dissolution method for warfarin sodium-aspirin combination tablets was
      developed which utilizes USP Apparatus 1 (baskets) at 50 rpm with 900 ml of
      phosphate buffer (pH 6.8; 0.05 M) medium at 37 degrees C. A reversed-phase liquid
      chromatographic method was also developed for the simultaneous determination of
      warfarin sodium, aspirin and salicylic acid on an octadecylsilica column using
      acetonitrile-tetrahydrofuran-glacial acetic acid-water (23:5:5:67, v/v/v/v) as
      the mobile phase with UV detection at 282 nm. Validation data were obtained which
      demonstrate that the dissolution methodology is accurate, precise, linear and
      rugged for the combination tablets.

PMID- 9278893
TI  - An enzyme inhibition assay for the quantitative determination of the new
      bisphosphonate zoledronate in plasma.
AB  - Zoledronate, 2-(imidazole-1-yl)-1-hydroxyethane-1,1-bisphosphonic acid is a new
      3rd generation bisphosphonate. A specific enzyme inhibition assay was developed
      for the determination of zoledronate in plasma of animals and man. The multistep
      synthesis of cholesterol and some of its precursors (lanosterol, squalene) from
      14C-labeled mevalonic acid lactone is catalyzed by the S12 fraction of
      homogenized rat liver in the presence of ATP, NADH and Mg2+. After hydrolysis of
      the reaction mixture with KOH, lipophilic reaction products were extracted with
      hexane and the overall yield determined by radiometry. Addition of zoledronate
      inhibited the formation of cholesterol and its precursors in a dose dependent
      manner. The described method is suitable to specifically and quantitatively
      measure concentrations of zoledronate down to 25 ng ml-1 in human and animal
      (dog, rat) plasma with acceptable reproducibility and accuracy.

PMID- 9278895
TI  - A direct technique for the simultaneous determination of 10 drug candidates in
      plasma by liquid chromatography-atmospheric pressure chemical ionization mass
      spectrometry interfaced to a Prospekt solid-phase extraction system.
AB  - New drug candidates are being synthesized at an ever increasing rate and, until
      recently, the pharmacokinetics of only a few of these could be evaluated. Our
      laboratory is taking a novel approach to rapid multiple pharmacokinetic screening
      of potential drug candidates in which mixtures of new substances are co
      administered to animals and analyzed simultaneously in plasma using liquid
      chromatography with tandem MS/MS detection in conjunction with a Prospekt
      automated on-line solid-phase extraction system. Plasma is sampled via an
      autosampler and extracted by the Prospekt with the eluent being introduced
      directly via a reverse phase HPLC column and a heated nebulizer interface to the
      mass spectrometer. Generic extraction and chromatographic conditions generally
      give good recoveries. The chromatographic run-times are less than 8 min. The
      accuracy and precision of these assays are carefully controlled with recoveries
      generally in the range 80-120% and coefficients of variation less than 20%. Lower
      quantifiable limits range from 2.5 to 5 ng ml-1. This approach considerably
      reduces the number of animals needed to screen drug candidates and its power is
      illustrated by determination of the pharmacokinetics of 10 substances after their
      simultaneous administration to dogs.

PMID- 9278896
TI  - On-line liquid chromatography coupled with high field NMR and mass spectrometry
      (LC-NMR-MS): a new technique for drug metabolite structure elucidation.
AB  - High performance liquid chromatography has been coupled simultaneously to high
      field NMR and MS detectors, giving UV, NMR and mass spectra for each component in
      a mixture, after on-line separation. This powerful new tool for the structure
      elucidation of components in mixtures without isolation has been successfully
      applied to the analysis of the metabolites of paracetamol in human urine.

PMID- 9278897
TI  - Determination of SR 49059 in human plasma and urine by LC-APCI/MS/MS.
AB  - SR 49059 ((2S 1-[(2R 3S)-5-chloro-3-(2-chlorophenyl)-1-(3, 4-dimethoxybenzene
      sulfonyl)-3-hydroxy-2,3-dihydro-1 H-indole-2-carbonyl]-pyrrolidine-2-carboxamide)
      is an orally active non-peptide vasopressin V1a antagonist. A sensitive,
      selective, and robust LC-MS/MS method was developed to determine the plasma and
      urine concentrations of SR 49059 in support of clinical studies. Plasma samples
      were prepared based on a rapid extraction procedure using Chem Elut cartridges.
      The extracted samples were analyzed on a C18 HPLC column interfaced with a
      Finnigan TSQ 700 mass spectrometer. Positive atmospheric chemical ionization
      (APCI) was employed as the ionization source. The analyte and its internal
      standard (2H6-SR 49059) were detected by use of multiple reaction monitoring
      (MRM) mode. The plasma matrix had a calibration range 0.2-20 ng ml-1, with within
      and between run accuracy and precision both less than 10%. The chromatographic
      run time was approximately 3 min. Urine samples were prepared based on a simple
      dilution with water, followed by analysis under the same conditions as plasma.
      The calibration range for urine matrix was 20-5000 ng ml-1, with within and
      between run accuracy and precision less than 11%. The method has been
      successfully applied to the clinical sample analysis. The plasma assay was also
      evaluated on a Finnigan TSQ 7000 mass spectrometer. The performance based on
      precision and accuracy was virtually identical to that on the TSQ 700, with the
      exception of linearity in calibration curve (the TSQ 700 was linear, the TSQ 7000
      was quadratic).

PMID- 9278898
TI  - Simultaneous determination of tenoxicam and 2-aminopyridine using derivative
      spectrophotometry and high-performance liquid chromatography.
AB  - Derivative spectrophotometry and high-performance liquid chromatography (HPLC)
      were used to determine tenoxicam and one of its decomposition products (2
      aminopyridine) simultaneously and in the presence of each other. The derivative
      procedure was based on the linear relationship between the tenoxicam
      concentration and the second derivative amplitudes at 390-348 nm (peak-to-trough)
      measurement. The 2-aminopyridine was determined through measuring the second
      derivative amplitude at 241 nm (zero-crossing for tenoxicam). For the HPLC
      procedure, a reversed-phase C8 column with a mobile phase composed of 0.02 M
      sodium acetate-methanol-acetonitrile (11:8:1) with 0.005 M heptane sulfonic acid
      sodium salt, as an ion pair, was used to separate both compounds with 2,4
      dinitrochlorobenzene, as an internal standard, in reasonable time. The flow rate
      was 1.5 ml min-1 with a programmable ultraviolet (UV) detection at 300 and 375
      nm. Both UV derivative spectrophotometric and HPLC approaches were followed for
      confirming the purity of tenoxicam in bulk and tablets dosage form.

PMID- 9278899
TI  - Size exclusion HPLC method for the determination of acidic fibroblast growth
      factor in viscous formulations.
AB  - A size exclusion HPLC method has been developed to determine the protein
      concentration of pharmaceutical formulations of recombinant acidic fibroblast
      growth factor (aFGF). These topical aFGF formulations not only contain low levels
      of protein mass (50 micrograms ml-1), but also include buffer ions,
      polysaccharide polyanions to conformationally stabilize aFGF and 1%
      hydroxyethylcellulose to increase the solution's viscosity. A cesium chloride
      mobile phase is utilized during SEC-HPLC to dissociate aFGF from the
      pharmaceutical excipients and to minimize nonspecific interaction of the protein
      with the column matrix. The protein content of a viscous aFGF formulation is
      determined by comparison of aFGF peak areas to standards of known concentration.
      Fluorescence spectroscopy was utilized to directly demonstrate that the protein
      remains in its native conformation during sample preparation and analysis.

PMID- 9278900
TI  - Adsorption of technetium-99m [99mTc] in the sample loop of an HPLC injection
      valve.

PMID- 9278901
TI  - A Chinese perspective of somatoform disorders.

PMID- 9278902
TI  - Post traumatic symptoms following medical illness and treatment.

PMID- 9278903
TI  - The reliability and validity of empirically scaled measures of
      psychological/verbal control and physical/sexual abuse: relationship between
      current negative mood and a history of abuse independent of other negative life
      events.
AB  - A history of psychological, physical, and sexual abuse, and circumscribed
      negative life events are precursors of current psychosomatic symptomatology.
      However, it is not known whether a history of abuse predicts current
      symptomatology, independent of other negative life events. We developed three new
      abuse scales: Psychological/Verbal; Control; and Physical/Sexual, which emerged
      when survey evidence of a random sample of the general public (N = 195) was
      factor analyzed. Test-retest reliabilities conducted on university students (N =
      62) were moderate to high: Psychological/Verbal (r = 0.86); Control (r = 0.76);
      Physical/Sexual (r = 0.74); and Negative Life Events (r = 0.84). A Negative Life
      Event scale was developed to measure the cumulative effects of events (over the
      lifespan). A total score was calculated by summing event scores, weighted in
      proportion to 11 independent judges' ratings of distress for later use (Kendall's
      W; chi 2 = 183.67, df = 67, p < 0.0001). Thirteen criterion measures of current
      symptomatology were administered to a subsample of the original sample (N = 92),
      and collapsed into one factor for use as the criterion in a regression analysis;
      results showed that, independent of negative life events and respondent
      demographics, the Psychological/Verbal and Control Abuse Scales predicted current
      negative mood and psychosomatic complaints, and the association between current
      symptomatology and the Physical/Sexual Abuse Scale approached, but did not
      achieve, statistical significance (t = 1.99, df = 71, p < .0501). The present
      study demonstrates that the three abuse scales may be powerful predictors of
      current symptomatology, and that they have the potential for further
      investigating a wider range of current medical, physiological, and psychological
      problems.

PMID- 9278904
TI  - Stage II breast cancer: differences between four coping patterns in side effects
      during adjuvant chemotherapy.
AB  - Fifty-six women with stage II breast cancer receiving adjuvant chemotherapy were
      recruited for a study evaluating and comparing coping patterns for differences in
      physical and psychological side effects during treatment with adjuvant
      chemotherapy. Cluster analyses were used to split women into confrontive,
      avoidant-confrontive, avoidant-resigned, and resigned coping clusters. Side
      effect measurements were taken on the day of adjuvant chemotherapy infusion and 3
      and 7 days later. Repeated measures ANCOVAs indicated that coping clusters
      predicted significant variance in physical, psychological, and total side effects
      when variance in covariates was held constant. Confrontive subjects reported
      significantly fewer psychological and physical symptoms than avoidant-confrontive
      and avoidant-resigned copers. Confrontive copers also reported fewer side effects
      than resigned copers, but this difference was not significant when differences in
      covariate distributions were controlled. Particularly robust differences were
      noted when confrontive copers were compared with avoidant-confrontive copers.
      Results suggest that a critical component in optimal coping may be a willingness
      to discuss and think about illness.

PMID- 9278905
TI  - Chest pain: heart, body or mind?

PMID- 9278906
TI  - Acute and chronic psychological risk factors for coronary syndromes: moderating
      effects of coronary artery disease severity.
AB  - This article provides a selective review of the effects of psychosocial factors
      and responses to acute mental stress on the onset of acute coronary syndromes.
      The literature suggests that the relationship between the anatomical severity of
      coronary artery disease (CAD) and likelihood of subsequent cardiac events, such
      as myocardial infarction, is not linear. Furthermore, evidence will be provided
      that the age-dependent associations between psychosocial factors and risk of
      cardiac events is at least in part mediated through the severity of underlying
      CAD. Finally, research will be summarized that supports the importance of both
      chronic psychosocial factors (e.g., low socioeconomic status and/or high
      hostility) and episodic psychological distress syndromes, such as vital
      exhaustion and depression. In reviewing this literature, two perspectives will be
      focused on: (1) the relationship between psychosocial factors and progressive
      CAD; and (2) the evidence concerning underlying pathophysiological mechanisms.

PMID- 9278908
TI  - Incidence and patterns of depression following coronary artery bypass graft
      surgery.
AB  - A number of studies have examined the impact of coronary artery bypass graft
      surgery (CABG) on mood by means of cross-sectional analyses. These studies have
      provided a "snapshot" view of the numbers of patients showing psychological
      disturbance. To examine both the incidence and patterns of depression, 121
      patients undergoing routine elective CABG were assessed preoperatively and
      postoperatively at 8 days, 8 weeks, and 12 months on the Beck Depression
      Inventory (BDI). The incidence findings suggested a small, transient increase in
      the number of patients with depression shortly after surgery. The preoperative
      score on the BDI was the best predictor of postoperative depression at all times
      of measurement. Discriminant function analysis on the patterns of depression
      indicated that trait anxiety maximally separated those patients who were
      depressed pre- and postoperatively from those only depressed shortly after the
      operation. The findings emphasize the value of examining patients' levels of
      anxiety and depression prior to surgery.

PMID- 9278907
TI  - Hostility, aggression and the risk of nonfatal myocardial infarction in
      postmenopausal women.
AB  - Hostility can predict coronary heart disease (CHD) and total mortality in men.
      However, in women this association has not been as thoroughly explored. This
      study examines whether hostile and aggressive attitudes are associated with
      myocardial infarction (MI) in postmenopausal women. Cases included 277 women who
      presented with an incident MI. Controls included a random sample of 988 female
      health maintenance organization enrollees. Women were asked the Hostile-Affect
      and the Aggressive-Responding factors of the Cook-Medley Hostility Scale. The
      Hostile-Affect score was linearly associated with increased risk for MI (odds
      ratio [OR] per point = 1.22; 95% confidence interval [CI95%] = 1.07-1.38),
      whereas the Aggressive-Responding score had a modest protective effect (OR = 0.92
      per point; CI95% = 0.84-1.02); p = 0.009. Adjustment for sociodemographic and MI
      risk factors altered these results only slightly. These hostility measures are
      easily administered, and could help to identify women who are at high risk for
      CHD and who may benefit from preventive measures.

PMID- 9278909
TI  - The effect of a psychological intervention program on the risk of a new coronary
      event after angioplasty: a feasibility study.
AB  - Restenosis after successful percutaneous coronary angioplasty (PTCA) is a major
      problem because it occurs in 25% to 35% of all patients. Because psychological
      factors, especially anger and vital exhaustion, have been found to increase the
      risk of new cardiac events after PTCA, a behavioral intervention might contribute
      to the reduction of the risk of restenosis. To investigate the operational and
      methodological aspects of a behavioral intervention, and to estimate the effect
      size of the risk reduction, we did a feasibility study of angioplasty patients
      who remained exhausted after PTCA. Breathing therapy was used as the main method
      for intervention. Thirty patients who participated in the intervention program
      and 65 controls were followed during an average period of 16 and 18 months,
      respectively. It was observed that the intervention resulted in a significant
      decrease of the mean exhaustion scores and reduced the risk of a new coronary
      event (cardiac death, coronary artery bypass grafting, myocardial infarction,
      rePTCA, restenosis) by 50% (chi = 2.19; p = 0.13). These results indicate that a
      clinical trial to test the hypothesis that a reduction of vital exhaustion and
      hostility reduces the risk of a new cardiac event after PTCA, is feasible and
      merits the efforts required.

PMID- 9278910
TI  - Natural history of upper cervical lesions in rheumatoid arthritis.
AB  - The natural history of the upper cervical lesions in rheumatoid arthritis (RA)
      was investigated, based on a follow-up study of 79 patients. At the beginning of
      this study, anterior atlantoaxial subluxation (AAS) was found in 35 patients, AAS
      combined with vertical subluxation (VS) in 34, and VS alone in 10. During the
      follow-up period (mean, 6.4 years), these lesions deteriorated in 30 of the 79
      patients. To evaluate the occipitoatlantoaxial relation, the angles between
      occiput and atlas (C0/C1 angle) and between atlas and axis (C1/C2 angle) were
      measured, and the correlation between these angles and deterioration of the
      lesions was investigated. The severity of RA was classified according to the
      "disease subset" advocated by one of us (T.O.): the least erosive subset (LES),
      the more erosive subset (MES), and the mutilating subset (MUD). There was a
      significant positive correlation between the C1/C2 angle and atlantodental
      interval (ADI) and a significant negative correlation between the C0/C1 angle and
      the ADI. This indicates that the atlas not only shifts forward but also slips
      down and forward at an incline from the axis. With an increase of the atlantal
      inclination, the anterior arch of atlas displaces in an anteroinferior direction,
      and VS combines with AAS. The development of associated VS lessens the amount of
      the ADI. At the advanced stage of the natural course, AAS is concealed, and VS
      alone is demonstrated. We concluded that the upper cervical lesion deteriorated
      in the order of AAS, AAS + VS, and VS alone. In patients classified as the LES
      subset, only AAS was found, and VS was never combined with AAS at the terminal
      stage. In patients in the MES, VS frequently combined with AAS. All patients who
      deteriorated to VS alone were ranked as MUD.

PMID- 9278911
TI  - Dorsal shift and expansion of the spinal cord after expansive open-door
      laminoplasty.
AB  - We investigated dorsal shift and anteroposterior spinal cord diameter after
      expansive open-door laminoplasty, comparing pre- and postoperative computed
      tomographic myelographic images to clarify the relationships between surgical
      outcome and these changes. Dorsal shift occurred at the midcervical spine in
      cervical spondylotic myelopathy (CSM) but was less extensive in ossification of
      the posterior longitudinal ligament (OPLL). Spinal cord anteroposterior diameter
      expanded for OPLL but did not for CSM. Correlation of outcome and dorsal shift
      was not significant for OPLL or CSM. Correlation of outcome and expansion was
      significant for OPLL, but not for CSM.

PMID- 9278912
TI  - Critical levels of spinal cord blood flow and duration of ischemia for the acute
      recovery of segmental spinal cord responses in cats.
AB  - A broad range of residual lumbar spinal cord blood flows assessed by laser
      Doppler flowmetry (rSCBF, 0-78%) was achieved by snare occlusion of the
      descending aorta and additional blood-volume reduction for 1-10 min in spinal
      cats (n = 30; 238 trials). The period of complete reflex suppression (delay until
      recovery) that revealed some correlation to duration (r = 0.72) and depth (r = 
      0.36) of ischemia showed comparable durations in mono- and polysynaptic reflexes,
      whereas it was significantly less for the cord dorsum potential (CDP). With rSCBF
      values > 50-60% reflexes and > 45%, the CDP was rarely abolished, irrespective of
      the duration of ischemia. The threshold of duration for a complete loss of reflex
      responses was found to be approximately 1 min of ischemia. The influence of rSCBF
      and duration of ischemia on the occurrence of incomplete recoveries of reflexes
      was assessed simultaneously in a logistic regression model. Compared with periods
      of ischemia of 3 min, all longer durations showed a steep risk gradient for
      incomplete recoveries; an increment of 10% in rSCBF led to a risk reduction for
      incomplete recoveries of nearly 25%. These findings were significant (p < 0.001)
      and indicated that blood-flow thresholds and limits for the development of
      neurologic deficits of the spinal cord are comparable to those of the brain, with
      the important difference that the blood-flow reserve of the spinal cord is
      smaller.

PMID- 9278913
TI  - Expansive laminoplasty for multilevel cervical OPLL.
AB  - Expansive laminoplasty is a new technique for the management of cervical
      ossification of the posterior longitudinal ligament (OPLL). Twenty patients were
      followed up for an average 3-year period. Follow-up examinations were performed
      every 3 months and at 1-year intervals. On lateral radiographs, the average
      increase in the anteroposterior (AP) diameter of the canal was 42%. Bone fusion
      was documented on computed tomography (CT) studies 3 months after surgery in 96%
      of patients. An average 83% of normal range of motion was preserved on long-term
      follow-up (3 years on average). Postoperative improvement over the same interval
      increased from an average preoperative Japanese Orthopaedic Association score of
      7.9 to 14.1 Expansive laminoplasty as described is safe and has a high fusion
      rate, while better preserving the normal range of motion.

PMID- 9278914
TI  - Intraoperative monitoring of spinal cord function using motor evoked potentials
      via transcutaneous epidural electrode during anterior cervical spinal surgery.
AB  - Because false-positive results are not infrequent when monitoring somatosensory
      evoked potentials during surgery, monitoring of motor evoked potentials (MEPs)
      has been proposed and successfully used during the removal of spinal cord tumors.
      However, this often requires direct visual placement of an epidural electrode
      after a laminectomy. We evaluated the use of MEPs, recorded via a
      transcutaneously placed epidural electrode, to monitor motor pathway functional
      integrity during surgery on the anterior cervical spine. Sixteen patients
      underwent anterior cervical vertebral decompression and fusion for cervical
      myelopathy and/or radiculopathy. Before surgery, an epidural monitoring electrode
      was placed transcutaneously at the midthoracic level and was used to record MEPs
      after transcranial cortical electrical stimulation. Electrode placement was
      successful in all patients but one, and satisfactory baseline spinal MEPs were
      obtained except for one patient who had cerebral palsy with significant motor
      dysfunction. Patients showed no significant changes in spinal MEPs during
      surgery, and all had baseline or better motor function postoperatively. None had
      complications from epidural electrode placement or electrical stimulation. We
      conclude that motor pathways can be monitored safely during anterior cervical
      spinal surgery using spinal MEPs recorded via a transcutaneously placed epidural
      electrode, that MEP preservation during surgery correlates with good
      postoperative motor function, and that cerebral palsy patients may possess too
      few functional motor fibers to allow MEP recording.

PMID- 9278915
TI  - Location of the vertebral artery foramen on the anterior aspect of the lower
      cervical spine by computed tomography.
AB  - Axial computed tomography scans were performed on 14 cadaveric cervical spines to
      determine the location of the vertebral artery foramen on the anterior aspect of
      the lower cervical spine. The best scan through the vertebral artery foramen from
      each level at C3-C6 was selected. Measurements of the vertebral artery foramen
      included the foramen depth, foramen width, interforaminal distance, the distance
      from the anterior border of the transverse foramen to the anterior border of the
      transverse process, the distance from the posterior border of the transverse
      foramen to the posterior border of the lateral mass, and the distance from the
      medial border of the vertebral artery foramen to the lateral border of the
      vertebral body. The results show that the average transverse foramen width was
      5.5 +/- 0.4 mm at C3, 5.7 +/- 1.0 mm at C4, 5.9 +/- 0.7 mm at C5, and 5.7 +/- 0.7
      mm at C6. The average transverse foramen depth and average interforaminal
      distance gradually increased from C3 to C6. The distance from the anterior border
      of the vertebral artery foramen to the anterior border of the transverse process
      gradually increased from C3 (1.2 +/- 0.4 mm) to C6 (2.7 +/- 0.8 mm) as well. The
      average distance between the medial border of the transverse foramina and the
      lateral border of the vertebral body for C3-C6 ranged from 1.8 to 2.2 mm. The
      average distance between the anterior borders of the vertebral artery foramina
      and the anterior border of the vertebral body gradually decreased from C3 (8.4 +/
      1.4 mm) to C6 (7.0 +/- 1.6 mm). This study suggested that the lateral border of
      the vertebral body may be a reliable landmark during anterior cervical
      decompression. The vertebral artery foramen should be free of violation if
      vertebrectomy or subtotal vertebrectomy is performed medial to the lateral border
      of the vertebral body.

PMID- 9278916
TI  - Quantitative anatomy of the cervical facet and the posterior projection of its
      inferior facet.
AB  - For this study, 41 cervical spines from C3 to C7 were directly evaluated.
      Anatomic evaluation of the cervical superior and inferior facets included the
      facet height, width, and angulation relative to the coronal plane. The projection
      of the inferior facet on the posterior aspect of the lateral mass was constructed
      and measured, and the dimensions of the lateral mass were evaluated. In general,
      the male linear parameters were larger than the female parameters, but the male
      angular dimensions were smaller than those of females. The posterior projection
      height of the inferior facet was found to be 7.4-9.0 mm from C3 to C7 for both
      sexes and was approximately 2 mm larger than half the height of the lateral mass.
      C6 and C7 had relative larger superior and inferior facet angles. The lateral
      mass was thinner at the level of C6-7. This study indicated that there may be a
      risk of violating the inferior articular facet and the related superior articular
      facet of the most caudal facet joint if a screw starting at the midpoint or below
      the midpoint of the lateral mass is directed perpendicular to the posterior
      aspect of the lateral mass at the level of C3-7.

PMID- 9278917
TI  - Instrumentation of the infected and unstable spine: a review of 17 cases from the
      thoracic and lumbar spine with pyogenic infections.
AB  - A retrospective review of 17 consecutive cases of spinal instrumentation for
      pyogenic vertebral osteomyelitis (PVO) with follow-up of > 2 years was
      undertaken, to describe the clinical course and outcomes in patients with
      instrumentation of actively infected spines. In 17 patients with PVO,
      instrumentation of the spine was performed during the period of clinical
      infection. Twelve of 17 patients were immunocompromised because of systemic or
      iatrogenic factors. Five patients had a history of malignancy and four had had
      spinal irradiation. In all 17 cases, the infection appeared to clinically be
      controlled after instrumentation. All patients were mobilized directly after
      instrumentation. The erythrocyte sedimentation rate returned to normal in 15
      patients without rheumatic disease and decreased by more than half in two
      patients with inflammatory arthritis. Four patients had died at follow-up, and
      none of these had signs of persistent infection. Eight cases had significant
      postoperative complications (47%), including two instrumentation failures and one
      wound dehiscence. Spinal instrumentation in selected cases of PVO allows early
      mobilization and did not seem to compromise the ability to clear infection. In
      certain recalcitrant cases, stabilization seemed to promote clinical resolution
      of the infection.

PMID- 9278918
TI  - Seat-belt use and relation to neurologic injury in motor vehicle crashes.
AB  - The relation between seat-belt use and neurologic injury was examined for the
      1,352 patients who had spinal injuries as the result of motor vehicle crashes and
      were subsequently admitted to the Midwest Regional Spinal Cord Injury Center at
      Northwestern University between 1971 and 1993. Intact lesions were observed in
      44% of patients (Frankel level E), complete lesions in 28% (Frankel A), sensory
      intact lesions in 8% (Frankel B), motor intact lesions in 5% (Frankel C), and
      functional motor lesions in 14% (Frankel D). Whereas only 14% of the sample were
      wearing seat belts, 60% of the belted and 41% of the unbelted vehicle occupants
      had intact lesions. The odds of surviving a motor vehicle crash with an intact
      injury were greater for patients who were wearing a lap or shoulder belt (odds =
      1.57) for women (odds = 0.63) and for patients whose injury occurred more
      recently (odds = 1.05). The relation between position in the vehicle and extent
      of injury was strongest for rear passengers: intact lesions were sustained by 73%
      of belted and 35% of unbelted rear passengers, whereas complete lesions were
      sustained by 9% of the belted and 21% of the unbelted rear passengers. In
      conclusion, seat belts appear to be an effective means of decreasing the extent
      of neurologic deficit in those sustaining spinal injuries caused by motor vehicle
      crashes. The results of this study support injury-prevention efforts that
      emphasize lap- and shoulder-belt use.

PMID- 9278920
TI  - Rigix plate system for anterior fixation of thoracolumbar vertebrae.
AB  - Only a few plate systems are available for anterior fixation of thoracolumbar
      vertebrae because of the difficulty in fastening a screw and a plate together. If
      the fixation is inadequate, the screws will become loose. The Rigix plate system
      consists of screws made of titanium alloy and a plate made of pure titanium. All
      screws used for internal fixation are screwed into the plate. This system permits
      the use of anchor screws, which facilitate exertion of force to compress the
      vertebral bodies together or to distract them from each other. In this study,
      Rigix plates were used in 24 patients (20 with burst fractures and 4 with
      metastatic tumors). In the 20 patients with fracture, internal fixation with a
      graft and a Rigix plate was performed after anterior decompression. In the four
      patients with malignant tumors, total spondylectomy was performed anteriorly and
      posteriorly, followed by implantation of a vertebral prosthesis, and then
      internal fixation with a Rigix plate combined posterior instrumentation with
      Diapson (Stryker Co., Tokyo, Japan) pedicular screws. Bone union was achieved in
      all patients. Neither breakage of instruments nor loosening of connections
      occurred in any case. In patients treated for bone metastases, the reconstructed
      spinal structure was able to be maintained for a long period. Of the screws used,
      five (5%) were not able to remain fixed as intended because they were inserted at
      inappropriate angles into the plate, but the fixation itself was excellent.
      Because of the low profile, ease of manipulation (mean instrumentation time was
      25 min), and compatibility with magnetic resonance imaging, the Rigix plate is
      useful for anterior fixation of thoracolumbar vertebrae.

PMID- 9278919
TI  - A new technique for the three-dimensional study of the spine in vitro and in vivo
      by using a motion-analysis system.
AB  - We introduce a new method with a motion-analysis system (MAS) to study the
      vertebral model in vitro. Compared with the currently most accurate technique,
      roentgen stereophotogrammetric analysis (RSA), the difference between the RSA and
      the MAS is 0.12 degree +/- 1.64 degrees. An accuracy with an error of 0.08 degree
      +/- 1.15 degrees is determined by means of an angle gauge. Although a significant
      difference between the MAS and the goniometer (p = 0.04) is found around the X
      axis (theta; transverse plane), it is limited to < 1 degree. The MAS provides an
      in-depth insight into the mechanism of the three-dimensional rotation at each
      vertebra in vivo. The backward inclination of the apical vertebra (AV) and
      forward inclination of the upper-end vertebra (UEV) around the Y-axis (phi)
      results in a correction of the hypokyphosis shown by the Cobb angle in the
      sagittal plane. The clockwise rotation of the UEV in the Z-axis (psi) leads to a
      reduction of the Cobb angle in the frontal plane. Additionally, the MAS as an
      intraoperative alternative shows different results of the derotation maneuver by
      the Cotrel-Dubousset instrumentation (CDI) compared with the computed tomography
      (CT) scan. Our method gives more direct details of the derotation not influenced
      by patient posture, as observed in the CT scan.

PMID- 9278921
TI  - Relationships between myoelectric activity, strength, and MRI of lumbar extensor
      muscles in back pain patients and normal subjects.
AB  - Eight normal individuals and eight patients with chronic back pain were
      evaluated. They undertook a treatment program lasting 8 weeks, with two exercise
      sessions each week. Myoelectric activity, lumbar extensor strength, and cross
      sectional magnetic resonance imaging appearance of the lumbar paraspinal extensor
      muscles was assessed at the beginning and end of the program. Initial baseline
      and final extensor strength measurements were done isometrically at seven points
      through full range. Surface myoelectric activity was monitored during both
      flexion and extension exercise. Subsequently, electromyographic (EMG) signals
      were analyzed for mean frequency (MPF) and amplitude (RMS). An average functional
      improvement of 65% and reduction of pain complaint of 41% occurred in the eight
      patients with chronic low back pain. Extensor strength improved an average of 48%
      contrasted to 6% for the normal subjects. Four patients who showed severe fatty
      infiltration in the extensors had a decrease in the degree of infiltration and no
      change in muscle mass. Changes in fatty infiltration did not correlate with
      strength changes. The dynamic EMG changes documented a decrease in amplitude
      (RMS) and a smaller decrease in frequency (MPF) for the same resistance when used
      at the beginning and end of the program. Structural changes in the muscles are
      not always needed to achieve strength gains or symptomatic improvement.

PMID- 9278922
TI  - Multidirectional stabilizing potential of BAK interbody spinal fusion system for
      anterior surgery.
AB  - Improvement in laparoscopic surgery requires spinal-fusion devices appropriately
      designed for this technique. The BAK interbody fusion device (Spine Tech Inc.,
      Minneapolis, MN, U.S.A.), which consists of two titanium screw cages, meets this
      requirement. Multidirectional stabilizing potential of this device was
      investigated by using an in vitro human cadaveric model. Four fresh-frozen human
      lumbosacral spine specimens (L5-S1) were used. The flexibility test consisted of
      applying six pure moments (flexion, extension, bilateral axial torques, and
      lateral bending moments) and measuring the ensuing three-dimensional motion.
      Moments were applied in four load steps: 0, 2.5, 5.0, 7.5, and 10.0 Nm, and for
      three load and unload cycles. Motion of the top vertebra was recorded during the
      third load cycle by using a three-dimensional optoelectronic motion-measurement
      system. The motion parameters studied were the ranges of motion (ROM) and the
      neutral zone (NZ). Comparing the ROM of the intact specimen and after the
      fixation, all motions except extension were reduced significantly (p < 0.005).
      Average percentage decrease in ROM were 45.8% in flexion, 40.4% in axial
      rotation, and 65.6% in lateral bending. The only significant changes in NZ were a
      255.7% increase in extension, a 90.9% increase in axial rotation, and a 70.8%
      decrease in lateral bending. This biomechanical study revealed that the BAK
      system provided decreases in ROM in all directions except in extension. The
      increased NZ in extension and axial rotation is most likely related to the
      positioning of the implant. Because these implants were placed from the anterior,
      damage to anterior annulus and anterior longitudinal ligament is inevitable. For
      clinical relevance, the patients undergoing this surgical procedure should avoid
      extension motions.

PMID- 9278923
TI  - Do musical hallucinations always arise from the inner ear?
AB  - It has been known for some time that musical hallucinations occur in deaf
      patients. This has been ignored, as it has been believed that neurological and
      psychiatric causes predominate. However, despite specific appeals, no one with
      musical hallucinations and a lesion in the brain but not in the ear has been
      produced. The postulated otological basis is a hyperactive state of the ear, a
      slight endolymphatic hydrops or pre-Meniere's disease. The hallucinations
      probably develop out of rhythmic tinnitus. A review of all the very disparate
      states and diseases supposedly causing musical hallucinations shows that
      peripheral ear symptoms are always present. It therefore seems that they always
      have the same simple otological trigger.

PMID- 9278924
TI  - Thalidomide may impede cell migration in primates by down-regulating integrin
      beta-chains: potential therapeutic utility in solid malignancies, proliferative
      retinopathy, inflammatory disorders, neointimal hyperplasia, and osteoporosis.
AB  - A growing number of human inflammatory disorders are reported to respond to
      treatment with thalidomide, and recently this drug has been shown to inhibit
      angiogenesis in the rabbit, in doses which can elicit teratogenicity in this
      species. Studies in marmosets and humans indicate that thalidomide, and a
      teratogenic analogue, decrease the expression of beta integrin subunits, most
      notably beta 3 and the beta 2 produced by leukocytes. Since integrins are crucial
      for cell-matrix interactions, and the beta 2 integrins of leukocytes mediate
      adhesion to endothelium, it is reasonable to postulate that thalidomide inhibits
      cell migration in susceptible species, and that this accounts for its anti
      inflammatory, anti-angiogenic, and teratogenic activity. This perspective
      suggests that thalidomide will show utility in the prevention or treatment of a
      wide range of disorders, including solid tumors, proliferative retinopathies,
      many inflammatory diseases, neointimal hyperplasia, and osteoporosis. It is
      likely that dietary fish oil-as well as selective inhibitors of urokinase, when
      and if they become clinically available-will complement the efficacy of
      thalidomide in most if not all of these applications.

PMID- 9278925
TI  - A neurobiological model for Tourette syndrome centered on the nucleus accumbens.
AB  - Tourette syndrome is a genetic disorder characterized by chronic multiple motor
      and vocal tics with a fluctuating course and modulated by internal and external
      environmental events. Tourette syndrome is more prevalent in males than females,
      and is associated with behavioural disorders such as obsessive-compulsive
      disorder and attention deficit hyperactivity disorder. Tourette syndrome symptoms
      are commonly attenuated by dopaminergic antagonists and adrenergic agonists, and
      usually exacerbated by psychostimulants. In this paper, I propose that
      dysfunction centered on the nucleus accumbens represents the neurobiological
      basis of Tourette syndrome. Recent evidence indicates that nucleus accumbens has
      a micro-organization characterized by modules of distinct neurochemical and
      neuroanatomical features. Our model assumes that external and internal events
      occurring during the development of the nervous system interact with products
      derived from the expression of the putative gene for Tourette syndrome, thereby
      inducing modular changes in nucleus accumbens. The clinical presentation,
      associated behavioural disturbances and response to drugs would depend on the
      pattern of modular dysfunction.

PMID- 9278926
TI  - Exploiting complementary therapeutic strategies for the treatment of type II
      diabetes and prevention of its complications.
AB  - Impaired glycemic control in type II diabetes results from peripheral insulin
      resistance, hepatic insulin resistance, and a relative failure of beta cell
      function. Nutritional and pharmaceutical measures are now available for
      addressing each of these defects, presumably enabling a rational and highly
      effective clinical management of non-insulin-dependent diabetes mellitus.
      Peripheral insulin resistance, which usually responds to a very-low-fat diet,
      aerobic exercise training, and appropriate weight loss, can also treated with
      high-dose chromium picolinate, high-dose vitamin E, magnesium, soluble fiber, and
      possibly taurine; these measures appear likely to correct the diabetes-associated
      metabolic derangements of vascular smooth muscle, and thus lessen risk for
      macrovascular disease. Metformin's clinical efficacy is primarily reflective of
      reduced hepatic glucose output; this action should complement the benefits of
      peripheral insulin sensitizers. When these measures are not sufficient for
      optimal control, beta cell function can be boosted with second-generation
      sulfonylureas.

PMID- 9278927
TI  - Loss of intraventricular fluid melatonin can explain the neuropathology of
      Alzheimer's disease.
AB  - Loss of intraventricular fluid melatonin explains why Alzheimer's disease
      neuropathology has a laminar, regional and neural-system-specific pattern, which
      includes the entorhinal cortex, CA1 of the hippocampus, the dorsal raphe nucleus
      and the locus ceruleus. High metabolic activity may be part of the neuronal
      vulnerability. Without elevated levels of ventricular fluid melatonin, the
      hydroxyl radical damages the mitochondria of the most active neurons, causing
      apoptosis, with resultant failure of the memory system. General brain atrophy
      follows in the absence of new memory formation.

PMID- 9278928
TI  - Genetic control of redundant systems.
AB  - Concepts from information theory are used to develop a model in which genes
      control highly redundant systems. One consequence is that mutations interact
      synergistically and there will be selection against zygotes which have several
      mutations in any one system. This could explain why total mutational load in the
      human genome remains constant even though there are several new mutations per
      generation. This model has implications for fertility, polygenic disease and
      cancer. It also explains a fundamental biological problem concerning the
      advantage of sexual over asexual reproduction.

PMID- 9278929
TI  - Simulation model of defective insulin receptors as byproducts of receptor
      recycling.
AB  - Our simulation model assumes that the defective insulin-binding receptors in non
      insulin-dependent diabetes (NIDDM) patients result from functional receptor
      recycling. The model is a short program written in MS DOS 5.0 Qbasic. MODEL
      DESIGN: Receptors with intracellular portions damaged in the process of recycling
      are considered defective since they bind insulin but do mediate insulin effects,
      or recycle. Their occurrence depends on the average activation rate of functional
      receptors. The insulin-binding receptors (defective and functional) are objects
      of slow and time-dependent turnover defined by the turnover rate. Recycled
      receptors rejoin functional receptors or enter the pool of defective receptors.
      The waste in the functional receptors' pool is covered by a limited amount of
      newly synthesized receptors. The defective receptors often accumulate in cases of
      increased activation of functional receptors. SIMULATION RESULTS: The insulin
      binding receptor quantity is determined, in the model, only by the number of
      newly synthesized receptors, reflecting the intensity of insulin stimulation.
      Synthesis is increased following variable insulin stimulations and decreased
      after sustained, intensive insulin stimulation. The number of functional
      receptors inversely reflects the average activation rate of functional receptors
      compared with the insulin-binding receptors turnover rate. High activation rates
      can diminish the proportion of functional receptors to less than 5% of that of
      all insulin-binding receptors. The model predicts that cells bearing only
      functional receptors show progressively shortened half-lives of receptors,
      reflecting the receptor activation intensity. On the other hand, cells bearing
      both defective and functional receptors show stable receptors' half-lives (20-36%
      of the defective receptors' half-life). Simulation results suggest that reduced
      functional receptor proportions in NIDDM patients might reflect the imbalance
      between the activation of functional receptors and the slow catabolism of
      defective receptors.

PMID- 9278930
TI  - Function of the human hymen.
AB  - The few existing hypotheses for the function of the human hymen are weak. These
      are briefly reviewed, and a new hypothesis is proposed. We suggest that the
      appearance of the juvenile human hymen is based on 'premature' birth, following
      which infant helplessness and a subsequent advantage for vaginal protection from
      external sources of infection allowed natural selection to increase its
      persistence well into juvenile life.

PMID- 9278931
TI  - Reported antiatherosclerotic activity of silicon may reflect increased
      endothelial synthesis of heparan sulfate proteoglycans.
AB  - Silicon plays a physiologically essential but mechanistically obscure role in
      promoting the synthesis of mucopolysaccharides and collagen. In light of reports
      that increased silicon ingestion impedes cholesterol-induced atherogenesis in
      rabbits and may be associated epidemiologically with reduced cardiovascular risk,
      it is reasonable to speculate that supplemental silicon may stimulate endothelial
      production of heparan sulfate proteoglycans that inhibit intimal hyperplasia.

PMID- 9278932
TI  - Sudden infant death syndrome: a proposed discovery.
AB  - Sudden cardiac death is a leading cause of fatality in the industrially developed
      world. Sudden infant death syndrome, has not hitherto been regarded as the same
      disease. However, the 55% reduction in the recorded rate of death from sudden
      infant death syndrome following the removal of stress-related problems caused by
      babies sleeping on their stomachs and overheating from tight and heavy clothing
      has, I propose, revealed that the babies may be dying from a similar stress
      related cause, which can be prevented.

PMID- 9278933
TI  - On the unreliability of the axiom of randomness: the case of random mutations in
      biology.
AB  - Logical scrutiny of the axiom of randomness argues against its reliability as an
      objective criterion for interpreting the insurgence of mutations in cancer cells.
      We propose that chaos theory is preferable because it is conceptually much more
      robust.

PMID- 9278934
TI  - Coronary artery spasm: a hypothesis on prevention by progesterone.
AB  - The mechanism of coronary artery spasm has been hypothesized as follows: the
      dormant gene of the smooth muscle of the human coronary artery is identical or
      similar to the active gene of the smooth muscle of ductus arteriosus, but can be
      activated by estrogen. The activation could be preventable by progesterone. The
      prevention is due to the reduction of the number of estrogen receptors of the
      smooth muscle of the coronary artery.

PMID- 9278935
TI  - Columnar analysis of sleep electroencephalogram.
AB  - During sleep, different rhythms appear in the electroencephalogram. The alpha
      rhythm was recently suggested to be the result when the excitability of the
      cerebral cortex is increased and decreased in order to keep the number of highly
      active columns within reasonable limits. It was found that the number most often
      is kept between four and five when awake. If the number is kept within other
      limits, the result will be different electroencephalogram rhythms. It is proposed
      that this is the explanation of the various rhythms during sleep.

PMID- 9278936
TI  - [Vasopressin: basic and clinical aspects].
AB  - Vasopressin (VP) is distributed in many parts of the brain. VP regulates the
      hypothalamo-pituitary-adrenal axis together with the corticotropin-releasing
      hormone. It closely follows a 24-h rhythm in the suprachiasmatic nucleus (SCN)
      and influences memory and behavior in the septum. clinical evidence suggests that
      VP might be related to depression and dementia. In this review, the central
      distribution of VP-containing cells, the physiological action of VP and related
      findings in depressed patients and demented patients are described.

PMID- 9278937
TI  - [Assessment of anti-tremorogenic drugs--nicotine-induced tail-tremor model].
AB  - The repeated administration of nicotine at small doses, which do not produce
      whole body tremor or convulsion, causes tremor only in the tail (tail-tremor) of
      rats. The tremor is accompanied by locomotor hyperactivity without rigidity and
      immobility of the whole body, suggesting that the nicotine-induced tail-tremor
      model is useful for studying the mechanism underlying tremor associated with
      movement. The tail-tremor induced by nicotine was suppressed by mecamylamine, a
      nicotinic antagonist, but not by atropine or scopolamine, muscalinic antagonists.
      Moreover, the tail-tremor was suppressed by the beta-blockers propranolol and
      pindolol, as well as the benzodiazepines diazepam and clonazepam. Tremor at rest
      is observed only in Parkinson's disease, which is improved with anti-muscalinic
      drugs. Essential tremor is one of the typical tremors connected with movement
      (postural and kinetic tremor) and is improved with beta-blocker. These findings
      and results suggest that nicotine-induced tail-tremor is useful for the study of
      essential tremor in animal models.

PMID- 9278938
TI  - [Relationship between learning behavior and genetic factor on immobility shown
      during forced swimming test].
AB  - The relationship between learning and genetic factor on immobility in mice during
      a forced swimming test (FST) has been studied. The duration of immobility during
      the FST did not change significantly after the administration of either
      scopolamine (2.5 mg/kg, ip) or cyclohexamine (150 mg/kg, ip), although both drugs
      produced impairment in the learning task. This suggests that the increase in
      immobility observed during the second trial of the FST may not be related to
      learning which could occur during the first trial. Concerning the strain
      difference, first, the duration of immobility in C3H mice was shorter than that
      in ICR, ddY, C57BL and BALB mice. Second, after receiving shock stress in a box,
      ICR, ddY and C57BL mice, but not C3H mice showed a marked decrease in locomotor
      activity when placed in the box again without shock. Also during the FST, both
      C57BL and ddY mice, but not C3H mice showed prolongation of immobility and
      reduction in swimming after shock stress. The changes in locomotor activity, and
      immobility and swimming during the FST caused by shock stress in ddY mice
      recovered to normal levels after treatment with imipramine. From these results,
      it is suggested that the immobility shown during the FST, which may be
      independent of learning and dependent on some genetic factor, is a suitable model
      of depression in animals.

PMID- 9278939
TI  - [Study of diazepam with quantitative EEGs taken with eyes opened and topography].
AB  - Diazepam is a representative drug of benzodiazepines. The subjects were 9 right
      handed healthy male volunteers 21 25 years of age. Double blind crossover trials
      with placebo control were conducted in a random sequence at an interval of 1
      week. Diazepam 10 mg and placebo were administered as single oral doses. Three
      minute EEGs were recorded with subjects' eyes opened before and 2 h after drug
      administration. One-minute out of the 3-minute EEGs was analyzed with FFT, and
      the absolute amplitude power (microV) was calculated. These results were
      subjected to Student's t-test (double difference) and displayed with topographic
      maps (t statistic significance probability mapping). Diazepam decreased the delta
      absolute amplitude power over left-parietal dominance, theta absolute amplitude
      power diffusely and alpha absolute amplitude power over parietal region
      dominance. It also increased the beta absolute amplitude power over left-antero
      temporal region dominance. The EEG profiles taken with subjects' eyes open were
      different from those of diazepam with eyes-closed vigilance controlled concerning
      the degree of decrease of delta and beta activities and region of the effect on
      alpha activity.

PMID- 9278940
TI  - [Relationship between cholinergic symptoms caused by distigmine and the
      activities of serum AChE and BChE].
AB  - Distigmine is widely used for the treatment of dysuria, which is caused by
      various types of psychotropic medications. Distigmine, however, is also known to
      induce adverse cholinergic effects, such as diarrhea and salivation, with a
      decreased level of serum cholinesterase. We evaluated the possibility of using
      serum acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) as specific
      clinical markers for the adverse cholinergic effects of distigmine. Of the twelve
      patients treated with distigmine for dysuria caused by psychotropic drugs six
      patients presented both adverse cholinergic effects and decreased levels of serum
      AChE and BChE. The other six presented neither of these changes. This study
      suggests that the values of serum AChE and BChE may be useful markers for the
      manifestation of adverse cholinergic effects caused by distigmine.

PMID- 9278941
TI  - Eosinophilic interleukin 5 (IL-5) transgenic mice: eosinophil activity and
      impaired clearance of Schistosoma mansoni.
AB  - Eosinophilia is a feature common to many invasive helminth infections and
      eosinophils are often considered to be effector cells in immunity to helminths.
      This study examined the possible influence of constitutive eosinophilia on the
      clearance of Schistosoma mansoni infections in mice. Eosinophils from interleukin
      5 transgenic mice exhibit normal ultrastructure and function with regard to
      phagocytosis and killing of bacteria and responses to chemotactic stimuli. IL-5
      transgenics and non-transgenic littermates were immunized once or four
      (hyperimmunization) times with irradiated cercariae of S. mansoni. Animals were
      challenged percutaneously with unirradiated cercariae one month after their last
      exposure to irradiated parasites. One month after challenge transgenic animals,
      whether unimmunized, vaccinated or hypervaccinated, carried significantly more
      liver-stage parasites than non-transgenic animals. These results suggest that
      although eosinophils from IL-5 transgenic mice are functional for a number of key
      parameters, large numbers of eosinophils and/or high levels of IL-5 may in some
      way impair clearance of S. mansoni. A re-evaluation of the roles of eosinophils
      and IL-5 in infections with this and other parasites may therefore be warranted.

PMID- 9278942
TI  - Blastogenic responses, interleukin-2 production and interleukin-2 receptor
      expression on CD4+ and CD8+ lymphocytes in rhesus monkeys experimentally
      inoculated with Loa loa.
AB  - To better understand cellular responses in loiasis infection, in vitro
      blastogenesis of peripheral blood mononuclear cells (PBMC) to filarial antigen
      was assessed in 12 Loa loa-inoculated rhesus monkeys over a two-year period.
      Cellular reactivity to antigen was observed between 10-35 weeks postinoculation
      (WPI), but had declined by week 50. The roles of interleukin-2 (IL-2) and IL-2
      receptor (IL-2R) expression of CD4+ and CD8+ T cells in regulating the response
      to antigen were examined during the initial (57 WPI) and late (92 WPI) time
      points of the observed diminished reactivity to antigen. The levels of IL-2 in
      antigen cultures at both time points were not significantly different from those
      in unstimulated cultures. Also, exogenous IL-2 partially reversed the PBMC
      response to antigen. The percentages of CD4+ and CD8+ T cells expressing IL-2R in
      antigen cultures at 57 WPI were not different from those of control animals.
      Likewise at 92 WPI, the percentage of CD4+ T cells expressing IL-2R in antigen
      cultures, were not increased above those of control animals. In contrast, the
      percentage of CD8+ T cells expressing IL-2R in antigen cultures were
      significantly increased above those of control animals (P < 0.0001), coinciding
      with an increase in CD8+ T cells numbers in these cultures. The data show that
      factors besides IL-2; and probably an imbalance in the percentages of CD4+ and
      CD8+ T cells bearing IL-2R in antigen cultures, may contribute to the diminished
      reactivity to antigen in L. loa-inoculated rhesus monkeys.

PMID- 9278944
TI  - In vitro infection with Theileria parva is associated with IL10 expression in all
      bovine lymphocyte lineages.
AB  - The protozoan parasite Theileria parva infects and transforms bovine lymphocytes,
      giving rise to a fatal lymphoproliferative condition known as East Coast fever.
      Although immune cattle mount strong cytolytic T lymphocyte responses to the
      parasite, naive animals appear unable to respond and develop severe
      immunopathological lesions. We have investigated the patterns of cytokine mRNA
      expressed by 19 bulk and cloned parasite-infected lymphoblast cell lines using a
      multiplex PCR system. Considerable variation was observed in the cytokine
      profiles of these lines and only IL10 was universally expressed. Investigation of
      cloned lines representing the major bovine lymphocyte populations failed to
      reveal a lineage-specific pattern of cytokine mRNA expression that could be
      associated with infection. Nonetheless, analysis of a CD4+ T cell clone before
      and after transformation with the parasite indicated that infection does alter
      the pattern of cytokine expression, with apparent upregulation of IL10. These
      observations raise the possibility that IL10 derived from infected cells may
      influence the immune responses of naive cattle to challenge.

PMID- 9278943
TI  - Expression of acquired immunity to the hookworm Ancylostoma ceylanicum in
      hamsters.
AB  - Four experiments are described in which hamsters, initially exposed to primary
      infection with Ancylostoma ceylanicum, were given a homologous challenge and
      components of the secondary response were quantified and compared to relevant
      control groups. The initial establishment of the L3 larvae was not prevented in
      immunized hamsters but their growth was slowed and virtually all larvae were lost
      within a week of challenge, when the majority were still at the L4 stage of
      development. The loss of worms was associated with an accelerated mucosal
      mastocytosis and increased systemic antibody. Thus acquired immunity to hookworm
      larvae in this system acted on L3 and L4 stages, thereby preventing larvae from
      maturing in immunized animals. In contrast to primary infections, immunized
      hamsters responding to a challenge infection did not lose weight nor did they
      experience significant anaemia, because of the lack of adult worms. The secondary
      immune responses therefore prevented manifestation of hookworm disease among
      immunized-challenged animals.

PMID- 9278945
TI  - Excretory/secretory products from plerocercoids of Spirometra erinacei reduce
      iNOS and chemokine mRNA levels in peritoneal macrophages stimulated with
      cytokines and/or LPS.
AB  - During infection with plerocercoids of Spirometra erinacei, organisms in the
      peritoneal cavity of infected animals have many bound inflammatory leukocytes yet
      survive apparently unharmed. Coculture of IFN gamma and LPS stimulated mouse
      peritoneal macrophages with live plerocercoids suppressed the mRNA expression of
      the inducible isoform of nitric oxide synthase (iNOS) and JE, the murine
      homologue of monocyte chemotactic protein-1 (MCP-1). Excretory/secretory (ES)
      products from plerocercoids also suppressed the induced iNOS and JE mRNA and
      reduced nitrite production of macrophages in a dose dependent manner. The
      suppression of inducible mRNA levels in macrophages cultured for 24 h with ES
      products varied with the nature of the stimuli; IFN gamma/ LPS-induced iNOS mRNA
      levels were effected less than were iNOS mRNA levels induced by IFN gamma/IL-2 or
      IFN gamma/ TNF alpha. Similar findings were obtained when nitrite production was
      measured. Thus modulation of LPS and cytokine inducible mRNA levels appear to be
      the primary target of ES products. We speculate that a major physiological role
      for this inhibitory activity in ES products might be the down regulation of pro
      inflammatory gene expression.

PMID- 9278946
TI  - Effect of praziquantel and oxamniquine treatment on human isotype responses to
      Schistosoma mansoni: elevated IgE to adult worm.
AB  - Pre- and post-treatment antibody isotype responses to Schistosoma mansoni adult
      worm and soluble egg antigens were compared in a study population previously used
      to show that IgE against adult worm correlates negatively with intensity of
      reinfection following chemotherapeutic cure. IgG subclass responses to adult worm
      were lower after treatment whereas IgM and IgE were higher. The increase in IgE
      to adult worm was observed with different preparations of adult worm, including
      the worm tegument, and with both praziquantel and oxamniquine therapy. No
      significant difference was observed between pre- and post-treatment isotype
      responses to egg antigens following either praziquantel or oxamniquine therapy.

PMID- 9278947
TI  - Inhibition can disrupt hypersynchrony in model neuronal networks.
AB  - 1. Model neuronal network simulations were performed using a reduced Traub
      neuronal network model. In the absence of inhibition the network produced
      synchronous population bursting. 2. Bursting of individual neurons was dependent
      on 1 or more of the following: build-up of charge in the dendritic compartment,
      prolonged current flow through simulated NMDA associated channels, current flow
      through T channels. Interburst interval duration and consequent burst frequency
      was dependent on the density of slow after-hyperpolarizing potassium channels. 3.
      Addition of an inhibitory interneuron population projecting to GABAA receptors
      resulted in rapid desynchronization of the population, generally after only 1-2
      cycles. This effect was found to be due to reduced participation in the
      individual population burst and to the need for multi-synaptic activation of the
      individual neuron in the presence of inhibition. 4. This desynchronizing effect
      could be offset by increasing the strength of interburst hyperpolarization either
      through increased density of IAHP, or through the addition of a separate
      inhibitory interneuron pool projected to GABAB receptors. 5. These data suggest
      that the synchronizing effects of inhibition may vary depending on circumstances
      with desynchronization being dominant in cases characterized by large population
      bursts such as those seen in epilepsy.

PMID- 9278948
TI  - The transient 40-Hz response, mismatch negativity, and attentional processes in
      humans.
AB  - 1. Recent experimental studies on the neurophysiological basis of auditory
      selective attention and sensory memory forming the sensory-data basis for tuning
      the selective-attention system in humans are reviewed. 2. The results demonstrate
      that the transient 40-Hz response is enhanced by selective attention, attenuated
      in the course of long-term stimulation, but is not affected by changes in
      auditory stimuli. 3. Therefore, the 40-Hz response seems to be closely related to
      selective and sustained attention, whereas it does not seem to be associated with
      passive attention, as it does not reflect the detection of changes in auditory
      stimuli. 4. Changes in auditory stimulation are registered by pre-attentive
      sensory memory, indexed by the mismatch negativity (MMN), a change-specific
      component of the event-related potentials (ERPs). By this time, the transient 40
      Hz response has already terminated. The magnitude of stimulus change is reflected
      in MMN latency. These latency changes predict changes in attentive reaction time
      (RT). 5. Thus, the pre-attentive memory mechanism seems to govern attentive
      detection of changes in the auditory environment. 6. It is concluded that the
      transient 40-Hz response is related to active attention and MMN is related to
      passive attention.

PMID- 9278949
TI  - Apomorphine induced alteration in corneofundal potentials in depression.
AB  - 1. The role of dopamine (DA) in mood regulation remains controversial. 2.
      Previous studies have examined DA sensitivity by measuring neuroendocrine
      responses following an agonist challenge. For the most part the results of such
      tests have failed to provide convincing evidence of a DA abnormality in affective
      disorders. 3. Neuroendocrine responses, however, are subject to complex
      regulatory influences and respond to DA systems which differ from those thought
      to modulate mood. 4. Recent animal and human studies suggest that light-dark
      adaptive electrical responses of the retinal pigment epithelium may serve as a
      better model of dopaminergic function. 5. The present study reports
      neuroendocrine and ocular results prior to, and following, an apomorphine (APO;
      0.75 mg sc) challenge in 12 depressed patients and 12 normal controls. 6.
      Apomorphine administration increased both light and dark retinal potentials in
      patients whereas those of controls decreased and this group difference was
      significant (p < 0.002). 7. No group differences were detected in any measure at
      baseline, or in prolactin, or growth hormone levels after the APO challenge. 8.
      The results indicate that the retina may serve as a more sensitive indicator of
      dopamine abnormalities in depressive illness.

PMID- 9278950
TI  - Abnormal cerebral perfusion in chronic methamphetamine abusers: a study using
      99MTc-HMPAO and SPECT.
AB  - 1. Cerebral blood flow of nine methamphetamine abusers with technetium-99m
      hexamethylpropyleneamine oxime (HMPAO) and single photon emission computed
      tomography (SPECT) as well as morphological examination with magnetic resonance
      imaging (MRI) were investigated. 2. Six of these subjects exhibited multiple
      focal perfusion deficits in cerebral cortices without abnormalities in MRI
      including cerebral atrophy and/or infarctions. 3. Cerebral perfusion deficits
      were detected in methamphetamine abusers even after a long abstinence period,
      suggesting that vascular changes were irreversible to some degree. 4. HMPAO SPECT
      study appeared to be sensitive to the detection of cerebral perfusion
      abnormalities in drug abusers.

PMID- 9278951
TI  - Abnormal plasma oxytocin and beta-endorphin levels in alcoholics after short and
      long term abstinence.
AB  - 1. Plasma oxytocin (OX), vasopressin (VP), estrone (ES) and beta-endorphin (beta
      end) levels were measured in 13 male non-chirrotic alcoholics, at 1, 4, 7, 15 and
      28 days after alcohol withdrawal and only once in 9 sex- and age-matched normal
      controls. 2. At all examined time points, plasma OX and ES, but not VP, levels
      were significantly higher in alcoholics than in controls. Alcoholics showed
      plasma beta-end levels lower than normal. 3. A positive relationship was found
      between ES and OX levels suggesting that elevated estrogens levels in chronic
      alcoholics might exert a stimulatory effect on OX. 4. In light of the well-known
      effect of OX on learning and memory, an involvement of OX in alcohol-induced
      neuropsychological deficits may be supposed.

PMID- 9278952
TI  - Plasma gamma-aminobutyric acid (GABA) predicts outcome in patients with alcohol
      dependence.
AB  - 1. Previous studies have suggested that low plasma GABA levels (< or = 100
      pmol/ml) may characterize a subset of patients with alcohol dependence. 2. In
      order to assess the clinical relevance of this biologic finding, the authors
      followed 49 alcohol dependent patients for up to 18 months following inpatient
      treatment. Treatment outcome was assessed by continuous abstinence and continued
      contact with research personnel. 3. Alcohol dependent patients with low plasma
      GABA had significantly better outcome than patients with plasma GABA in the
      normal control range (101-150 pmol/ml). 4. These findings suggest that plasma
      GABA measures may prove to be clinically useful in identifying alcohol dependent
      patients at risk for relapse.

PMID- 9278954
TI  - Effect of no synthesis inhibition on striatal dopamine release and stereotyped
      behavior induced by a single administration of methamphetamine.
AB  - 1. The authors performed both microdialysis and behavioral measurement in each of
      rats, in order to examine effects of nitric oxide synthase inhibitor, N omega
      nitro-L-arginine methyl ester (LNAME;30 mg/kg,i.p.) on striatal dopamine (DA)
      release and stereotypy induced by a single administration of methamphetamine
      (MA)(4 mg/kg,s.c.), simultaneously. 2. LNAME administered prior to MA
      significantly decreased level of locomotion-stereotypy rating scores induced by
      MA. 3. In the same animals, LNAME had no effect on MA-induced striatal DA
      release. 4. The results suggest that NO synthesis inhibition attenuated MA
      induced stereotypy by modulating neuronal process subsequent to activation of
      postsynaptic DA receptors.

PMID- 9278953
TI  - An association between increased serum-soluble interleukin-2 receptors and a
      disturbance in muscle force in schizophrenic patients.
AB  - 1. Serum-soluble interleukin-2 receptors (SIL-2Rs), a sign of immune activation,
      are increased in approximately 30% of schizophrenic subjects. 2. In a recent
      publication the authors found that SIL-2Rs were particularly elevated in
      schizophrenic subjects with tardive dyskinesia (TD). 3. This paper investigates
      the relationship between muscle force instability and SIL-2Rs in 32 schizophrenic
      patients, 10 of whom were neuroleptic-naive. 4. The authors hypothesized that
      there would be a positive correlation between increased levels of SIL-2Rs and
      muscle force instability. 5. Serum SIL-2Rs and muscle force instability were
      positively correlated (r = 0.54, p < .001) in the schizophrenic patients, and
      this correlation held even for the subset of neuroleptic-naive patients (r = .73,
      df 8, p = .016). 6. These findings suggest that there is an important correlation
      between immune activation and muscle force instability in schizophrenic patients.

PMID- 9278955
TI  - Dissociation of locomotor and conditioned place preference responses following
      manipulation of GABA-A and AMPA receptors in ventral pallidum.
AB  - 1. This study examined the roles of GABAergic and glutamatergic neurotransmission
      in ventral pallidum (VP) in conditioned place preference and locomotor activity.
      2. Picrotoxin (0.1 microgram), a GABA antagonist, and (+/-)alpha-amino-3-hydroxy
      5-methylisoxazole-4-propionate (AMPA; 0.14 microgram), a non-NMDA glutamatergic
      agonist, were injected bilaterally into VP through implanted cannulae. 3. Both
      drugs produced a robust increase in locomotion, but neither produced conditioned
      place preference. 4. These results suggest a dissociation of locomotor activity
      and reward at the level of ventral pallidum. In addition, it was argued that the
      GABAergic projection from nucleus accumbens to ventral pallidum may not be
      involved in the processing of reward initiated from dopaminergic activation in
      nucleus accumbens.

PMID- 9278956
TI  - Attenuation of the locomotor activating effects of D-amphetamine, cocaine, and
      scopolamine by potassium channel modulators.
AB  - 1. Locomotor activating effects of D-amphetamine, cocaine, and scopolamine were
      determined alone and after pretreatment with K-channel modulators in mice. 2.
      When administered alone, D-amphetamine (1.0- 30 mg/kg) and cocaine (3.0- 56
      mg/kg) produced inverted U-shaped dose-effect curves characteristic of
      psychomotor stimulant drugs. 3. When administered alone, scopolamine (3.0-56
      mg/kg) also produced dose-dependent increases in locomotor activity but these
      effects plateaued with similar increases in locomotor activity induced by 10-56
      mg/kg of scopolamine. 4. Pretreatment with the K-channel blockers 4-aminopyridine
      (0.3-1.7 mg/kg), quinine (30-100 mg/kg) or apamin (0.3-1.0 mg/kg) attenuated the
      locomotor increases induced by d-amphetamine, cocaine, and scopolamine. 5. Like
      the K-channel blockers, pretreatment with the K-channel openers cromakalim (1.0
      3.0 mg/kg) and pinacidil (3.0-10 mg/kg) also attenuated the locomotor increases
      induced by D-amphetamine and scopolamine but did not modify the locomotor
      activating effects of cocaine. 6. These results demonstrate that K-channel
      modulation modifies the effects of D-amphetamine, cocaine, and scopolamine. 7.
      The results also demonstrate that K-channel openers can differentially alter the
      behavioral effects of cocaine and D-amphetamine.

PMID- 9278957
TI  - U-95666E: a potential anti-parkinsonian drug with anxiolytic activity.
AB  - 1. U-95666E, a D2 selective dopamine agonist, was investigated for its effect on
      rat striatal acetylcholine (ACh) concentration and the results were compared with
      those obtained with pergolide, pramipexole and bromocriptine under similar
      conditions. 2. U-95666E, pergolide, pramipexole and bromocriptine dose
      dependently increased striatal ACh concentration both in the non-reserpinized and
      reserpinized rats. 3. Intrinsic activity of U-95666E was similar to pergolide and
      pramipexole in non-reserpinized rats, but significantly lower in reserpinized
      rats. 4. The sensitivity of these dopamine agonists for increasing ACh levels in
      the denervated as compared to innervated striatum were significantly (p < 0.01)
      higher. 5. U-95666E also has anxiolytic activity in mice. 6. In conclusion, U
      95666E may have potential for the treatment of Parkinson's Disease and associated
      anxiety.

PMID- 9278959
TI  - [The effects of judge's roles on probability judgment].
AB  - A number of studies on probability judgment have reported that people often tend
      to neglect the base-rate in the Cab Problem (Bar-Hillel, 1980). To explain the
      base-rate neglect, the present research hypothesized that subjects presented with
      the Cab Problem focused on the case information in the problem, because the
      subjects were asked to estimate probability based on that particular case. In
      'two experiments, subjects' individuated or general interpretation of the Cab
      Problem was manipulated by instructing the subjects to play either responsible or
      neutral judge's role, respectively. The results suggested that in the responsible
      judge condition the case information had large impact on subjects' judgment,
      whereas in the neutral judge condition it did not. These results implied that the
      subject's base-rate neglect arose from taking the individuated interpretation.

PMID- 9278958
TI  - Comparison of sensitization elicited by amphetamine and pertussis toxin:
      characterization of locomotor behavior and limbic dopamine release.
AB  - 1. Male, Sprague-Dawley rats were pretreated with one of several regimens of
      repeated, intermittent amphetamine or with a single-dose of intra-VTA pertussis
      toxin (PTX). 2. An amphetamine challenge dose (0.5 mg/kg, i.p.) produced
      increased locomotor activity in both amphetamine and pertussis toxin-pretreated
      rats. 3. The magnitude of activity in PTX pretreated rats exceeded 5-fold that of
      the amphetamine-pretreated rats. 4. There were no significant differences in the
      levels of sensitized behavior elicited by 4 distinct amphetamine pretreatment
      protocols. 5. Neither of the drug pretreatments caused significant changes in the
      ability of 10 microM amphetamine to promote dopamine efflux from nucleus
      accumbens or striatal tissue in vitro. 6. The sensitized behaviour cannot be
      explained by in vitro alterations in pre-synaptic dopamine release, which may
      suggest an up-regulation of post-synaptic activity.

PMID- 9278960
TI  - [Effects of NMDA antagonist, MK-801 on spatial exploratory behavior in the rat].
AB  - Rats given an antagonist against N-methyl-D-aspartate, (+)-10, 11-dihydro-5
      methyl-5H-debenzo (a, d) cycloheptene-5, 10-imine (MK-801), were compared with
      control rats for their activity and exploratory behavior (habituation,
      exploration time to the spatial change of one of 4 objects and to the new object)
      in a circular open field. Rats given 0.07 mg/kg dose of MK-801 displayed no
      significant differences with the controls. Rats given 0.1 mg/kg dose of MK-801
      failed to respond to the spatial change, whereas they displayed habituation and
      exploration to the new object at the same degree as the control rats. Rats given
      0.3 mg/kg dose of MK-801 displayed hyperactivity and did not display habituation
      and exploration. The result suggests that the 0.1 mg/kg dose of MK-801, which
      dose not affect on activity, habituation and exploration to the new object in
      rats, selectively affects on acquisition of spatial information and reduces their
      spatial exploration.

PMID- 9278961
TI  - [What children think about their growth: the sense of growth and Loevinger's ego
      developmental level].
AB  - This study concerns the sense of growth that children have of themselves, and
      attempted to show that differences in it can be explained in terms of ego
      developmental levels proposed by Loevinger. Seven hundred ninety-nine (799)
      children between 5th and 12th grades responded to a Sentence Completion Test
      (SCT) of ego development and sense of growth. Five ego developmental levels were
      identified: Impulsive, Self-Protective, Self-Protective/Conformist, Conformist,
      and the Self-Aware. The results confirmed the higher the age, the higher the ego
      developmental level, and the level affected what children thought about their
      growth. The answers to the SCT of low ego-development children had more overt
      characteristics such as physical development, whereas those of high children
      tended to include more covert aspects such as mental development.

PMID- 9278962
TI  - [A study of information processing of cognitive conflict using event-related
      potentials].
AB  - This study examined whether cognitive conflict, reported by Eriksen and Eriksen
      (1974), could be explained by a model of reciprocal inhibition between correct
      and incorrect response preparation. Subjects responded selectively to a central
      target letter with flanking compatible (e.g., HHHHH) or incompatible (e.g.,
      SSHSS) noise letters. In the mixed condition all four stimuli were mixed randomly
      in a block, and in the blocked condition only two stimuli with identical noises
      were used. The results showed that the reaction times to incompatible stimuli
      were delayed in the mixed condition compared with that to compatible stimuli,
      while the delay was significantly reduced in the blocked condition. This blocking
      effect was also shown on P3 latencies, an event-related potential measure of
      stimulus evaluation, but not on lateralized readiness potentials (LRPs), a
      measure of response preparation. Furthermore, irrespective of blocked/mixed
      conditions, LRPs indicating incorrect preparation were observed. These findings
      suggest that cognitive conflict could not be explained by the reciprocal
      inhibition model based on response preparation, but by a model based on stimulus
      evaluation.

PMID- 9278963
TI  - [A developmental study on children's understanding of emotion and emotional self
      control].
AB  - The present study examined how children understand the processes concerning the
      strategic control of emotion. There are five components of this emergent
      metaemotive understanding: the children's knowledge of (1) the cues for
      identifying emotions, (2) the antecedents of emotions, (3) display rules, (4) the
      consequence of an emotional response, and (5) the strategies of emotional self
      control. Five, seven and nine-year-old children were interviewed regarding their
      knowledge of these components. The following results were obtained. For
      identifying emotion, seven-year-olds tended to focus on the situational cues.
      Nine-year-olds were more likely to focus on the mental cues. The frequency of
      spontaneous usage of display rules increased with age. Nine-year-olds mentioned
      the cognitive self-control strategies such as re-directing their thoughts. The
      results were discussed in terms of developmental perspectives.

PMID- 9278964
TI  - [Intergroup discrimination and illusory correlation induced by social category:
      minority, majority, and outsider].
AB  - Two experiments were conducted to examine intergroup discrimination and illusory
      correlation in majority and minority members and outsiders of a group. In
      Experiment 1, allegedly based on social attitudes, 64 participants were divided
      into the three groups, and then completed a point distribution task in a minimal
      group paradigm. It was found that although both minority and majority members
      showed ingroup favoritism, outsiders favored neither majority nor minority. In
      Experiment 2, a continuation of Experiment 1, 45 statements were shown that
      described majority and minority members in favorable and unfavorable terms. The
      majority members perceive illusory correlations between the minority group and
      infrequent, unfavorable characteristics, whereas the minority members did not.
      The results suggest that for the majority, both distinctiveness-based cognitive
      bias and ingroup bias had the same effects on perception of illusory correlation,
      whereas for the minority, the two had opposite effects. The outsiders did not
      perceive any illusory correlation.

PMID- 9278965
TI  - [Recognition processes for Chinese and original words written in Hangul].
AB  - The purpose of this study is to examine recognition processes for Chinese and
      original words written in Hangul. It was tested whether or not the processing
      time for Chinese words is different from that for original words. In the first
      experiment, naming latencies for Chinese words were longer than those for
      original words. Also, the naming latencies for high-frequency-Chinese-words with
      final consonant (CVC + CVC) were shorter than those for high-frequency-Chinese
      words without final consonant (CV + CV). The second experiment was conducted to
      clarify the lexical process by using the lexical decision task. The lexical
      decision times for Chinese words were not different from those for original
      words. The data suggest that the reading of Hangul words is mediated by lexical
      information as well as by phonological information.

PMID- 9278966
TI  - [Expectation of others' reward allocation, and ingroup favoritism in reward
      allocation].
AB  - The purpose of this study was to investigate people's expectation of others'
      ingroup favoritism, and the effect of expecting others to take part in reward
      allocation decision on ingroup favoritism in reward allocation. Subjects were
      randomly assigned to two groups, and were asked to rate attractiveness of ingroup
      members, and to allocate reward to ingroup and outgroup under two conditions. In
      the unilateral condition, the subject alone was to make the decision, and in the
      multilateral condition, every subject was to. The results indicated that equally
      in all conditions, subjects rated ingroup members more attractive, and expected
      others to allocate more reward to own groups. Reward allocation that favored
      ingroup occurred only under the multilateral condition, where everyone
      participated in reward allocation, regardless of whether the subject's own reward
      was dependent on others' decisions or was a fixed amount. The findings suggest
      that ingroup favoritism was not a result of quasi-strategy of self-interest in an
      attempt to maximize own gains, but of psychological group formation.

PMID- 9278967
TI  - [Facilitation effects of an auditory accessory stimulus on visual reaction time].
AB  - Visual reaction time (RT) is reduced when the visual stimulus is paired with an
      auditory stimulus. This auditory stimulus is accessory in the sense that subjects
      need not to pay attention to it in the visual RT task. This study examined how
      the facilitation effect of the auditory accessory stimulus changes with varying
      the stimulus onset asynchrony (SOA) between the two stimuli, and their
      intensities. The results showed that RTs are reduced as the visual stimulus is
      preceded by the auditory stimulus. Furthermore, RTs are transiently reduced when
      the two stimuli are presented at the same time. The magnitude of this
      facilitation is directly proportional to the intensity of the auditory stimulus
      and is inversely proportional to that of the visual stimulus. These findings
      suggest that there are two different kinds of facilitation effects on visual RTs
      made by the auditory accessory stimulus.

PMID- 9278968
TI  - Toxins affecting calcium channels in neurons.
AB  - Calcium enters the cytoplasm mainly via voltage-activated calcium channels
      (VACC), and this represents a key step in the regulation of a variety of cellular
      processes. Advances in the fields of molecular biology, pharmacology and
      electrophysiology have led to the identification of several types of VACC
      (referred to as T-, N-, L-, P/Q- and R-types). In addition to possessing
      distinctive structural and functional characteristics, many of these types of
      calcium channels exhibit differential sensitivities to pharmacological agents. In
      recent years a large number of toxins, mainly small peptides, have been purified
      from the venom of predatory marine cone snails and spiders. Many of these toxins
      have specific actions on ion channels and neurotransmitter receptors, and the
      toxins have been used as powerful tools in neuroscience research. Some of them
      (omega-conotoxins, omega-agatoxins) specifically recognize and block certain
      types of VACC. They have common structural backbones and some been synthesized
      with identical potency as the natural ones. Natural, synthetic and labeled
      calcium channel toxins have contributed to the understanding of the diversity of
      the neuronal calcium channels and their function. In particular, the toxins have
      been useful in the study of the role of different types of calcium channels on
      the process of neurotransmitter release. Neuronal calcium channel toxins may
      develop into powerful tools for diagnosis and treatment of neurological diseases.

PMID- 9278969
TI  - Toxins isolated from the venom of the Brazilian coral snake (Micrurus frontalis
      frontalis) include hemorrhagic type phospholipases A2 and postsynaptic
      neurotoxins.
AB  - Toxins isolated from the venom of the Brazilian coral snake (Micrurus frontalis
      frontalis) include hemorrhagic type phospholipases A2 and postsynaptic
      neurotoxins. Toxicon 35, 1193-1203, 1997.-Two sets of proteins have been purified
      from the venom of the Brazilian coral snake, Micrurus frontalis frontalis. One
      set has mol. wts, as shown by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE), in the 8000-13,000 range and includes some proteins
      which are toxic to mice and others which are not. These proteins appear to be
      isoforms of postsynaptic toxins. The other set shows phospholipase A2 (PLA2)
      activity and the toxic members of this set promote hemorrhage in mice in a manner
      closely resembling that produced by PLA2s isolated from the venom of the
      Australian tiger snake (Notechis scutatus scutatus). These PLA2s migrate on SDS
      PAGE with apparent mol. wts in the 18,000-22,000 range which is characteristic of
      PLA2s that have an alpha-helix D similar to pancreatic PLA2s. Elapid venom PLA2s
      of the type which typically migrate on SDS-PAGE with mol. wts in the 13,000
      16,000 range and do not have alpha-helix D have not been detected in M. f.
      frontalis venom.

PMID- 9278970
TI  - A new phospholipase A2 isoform isolated from Bothrops neuwiedii (Yarara chica)
      venom with novel kinetic and chromatographic properties.
AB  - A new phospholipase A2 isoform, called P-3, isolated from Bothrops neuwiedii
      (Yarara chica) venom, showed different chromatographic, enzymatic and cytotoxic
      properties compared to the previously purified isoforms P-1 and P-2 but it had a
      similar edema-inducing activity. In contrast to previously reported B. neuwiedii
      phospholipase A2 isoforms, P-3 did not interact with the oligosaccharide matrix
      of gel filtration columns (Superose, Superdex). Its molecular weight was 15,000
      and its N-terminal 14 amino acid sequence was Asn-Leu-Val-Gln-Phe-Glu-Thr-Leu-Ile
      Met-Lys-Ile-Ala-Gly. Amino acid analyse revealed the presence of an unique
      histidine, presumably located at the active site, because a full inhibition of
      enzymatic activity was observed after treatment with p-bromophenacyl bromide. The
      new isoform also differentiated in its surface pressure activity profile when
      assayed in lipid monolayers. P-3 had an optimum activity towards
      dilauroylphosphatidylcholine monolayers of 27 mN/m and a cut-off pressure of 30
      mN/m, whereas P-1 and P-2 had an optimum of 13 mN/m with a cut-off of 22 mN/m. P
      3 retained its edema-inducing activity in the absence of hydrolytic activity,
      suggesting that the inflammatory activity was not dependent on the enzymatic
      activity. Neither the enzymatic nor the edema-inducing activity was affected by
      heparin. The new isoform was not lethal when a single dose of 5 micrograms/g body
      weight was injected intraperitoneally into mice. All of the isoforms displayed
      cytotoxic activity in vitro on B16F10 melanoma cells evaluated by direct MTT
      assay, with an EC50 of 31 micrograms/ml for P-3 and of 15 micrograms/ml for P-1
      and P-2. The cytotoxic activity of P-3 was inhibited by p-bromophenacyl bromide
      treatment of the enzyme (up to 170 micrograms/ml), whereas the same treatment on
      P-1 and P-2 changed their EC50 to 60 micrograms/ml. The difference observed with
      inhibited enzymes suggests a different mechanism for the cytotoxic action of P-3
      with respect to P-1 and P-2.

PMID- 9278971
TI  - Convulxin, a potent platelet-aggregating protein from Crotalus durissus
      terrificus venom, specifically binds to platelets.
AB  - Convulxin, a very potent aggregating protein from rattlesnake venom, was purified
      by a new procedure and its heterodimeric structure alpha 3 beta 3 was confirmed.
      The polypeptide N-terminal sequences of convulxin subunits were determined by
      Edman degradation. They are very similar and appear homologous to botrocetin from
      Bothrops jararaca venom and to rattlesnake lectin from Crotalus atrox venom, both
      being classified among the C-type lectin family. The binding of 125I-labelled
      convulxin to blood platelets has also been analysed under equilibrium conditions.
      These studies indicated that convulxin binds to platelets with a high affinity
      (Kd = 30 pM) on a small number of binding sites (1000 binding sites per cell).
      The high-affinity binding of convulxin appears specific to platelets, since it is
      not observed on other cell types such as neutrophils and erythrocytes. Also, the
      high-affinity binding of convulxin to membranes platelet is not inhibited by
      alpha-thrombin, fibrinogen, collagen, laminin binding inhibitor, RGDS peptide,
      adenosine diphosphate, platelet-activating factor-acether, serotonin or
      epinephrine. This, together with the recent observation that platelet activation
      by convulxin is partially mediated by phospholipase C and involves other
      mechanisms as well, indicates that convulxin may interact with a specific
      platelet acceptor (receptor) protein which has yet to be characterized.

PMID- 9278972
TI  - Purification and stability studies of immunoglobulins from Lachesis muta muta
      antivenom.
AB  - Immunoglobulins were isolated from hyperimmune horse plasma against Lachesis muta
      muta venom by ammonium sulfate precipitation and immunoaffinity technique
      (Sepharose-venom L. m. muta column). When necessary, limited proteolysis with
      pepsin was used to generate a bivalent antigen-binding fragment (F(ab')2).
      Solutions with immunoglobulins or F(ab')2 fragments were fractionated by
      molecular filtration chromatography (Superose 12) and the expected mol. wt
      species were observed. The L. m. muta venom shows caseinolytic and haemorrhagic
      activities. Incubation of the venom with these purified antibodies resulted in a
      decrease of both activities. High temperatures promote aggregation and the
      formation of protein precipitates. Sorbitol (1.0 M) was used as an osmolyte (a
      natural substance or an organic compound capable of stabilizing proteins) and
      decreased the formation of protein precipitates in solutions of antibodies, as
      judged by a spectrophotometric assay (280 nm), by nephelometry or when tested by
      enzyme-linked immunosorbent assay. Circular dichroism was used to study the
      spectra of antibodies in the presence of phosphate-buffered saline or sorbitol.
      Up to an osmolyte concentration of 1.0 M, there was no significant perturbation
      of the F(ab')2 fragments spectra in the amide region. However, whole
      immunoglobulins in the presence of 1.0 M sorbitol presented a small spectral
      perturbation, suggesting that the beta-structure was reinforced. The effect of
      osmolyte on the affinity of antibodies was observed by enzyme-linked
      immunosorbent assay. There was no significant difference in the results when the
      antibodies were previously incubated with venom in phosphate-buffered saline or
      in the presence of 1.0 M sorbitol. In conclusion, an osmolyte (sorbitol) was
      shown to be capable of stabilizing antibodies at high temperatures, with no
      significant perturbation in the secondary structure or affinity to L. m. muta
      venom. These results point to the possibility of using sorbitol, or other
      osmolytes, as stabilizers of immunoglobulin preparations.

PMID- 9278973
TI  - Isolation and purification of superbins I and II from Austrelaps superbus
      (copperhead) snake venom and their anticoagulant and antiplatelet effects.
AB  - Two proteins with anticoagulant and antiplatelet activities were purified from
      Austrelaps superbus (copperhead) venom by gel filtration, ion-exchange and
      reverse-phase chromatographic methods. These purified proteins were designated
      superbins I and II. Superbin I was homogeneous, as indicated by electrospray
      ionization-mass spectrometry, with a mol. wt of 13,252.3 +/- 1.6, whereas
      superbin II contained two closely related proteins of mol. wts 13,235.5 +/- 1.1
      and 13,212.9 +/- 1.2. Both superbins showed phospholipase A2 activity and
      exhibited weak anticoagulant effects when tested by one-step prothrombin time
      clotting assays. The 'dissection approach' was used to identify the coagulation
      complex(es) inhibited by these enzymes in the extrinsic coagulation cascade. The
      results indicate that both the enzymes inhibit the extrinsic tenase complex, but
      not the prothrombinase complex, similarly to other weakly anticoagulant
      phospholipases. Superbins I and II also inhibited aggregation of human platelets
      induced by collagen.

PMID- 9278974
TI  - Resistance of the Egyptian mongoose to sarafotoxins.
AB  - The Egyptian mongoose (Herpestes ichneumon) is known for its resistance to
      viperid and elapid venoms. The current work demonstrates that it is also
      resistant to the venom of Atractaspis and its most toxic component, sarafotoxin
      b. Intravenous administration of this toxin, at a dose of about 13 times LD100
      for mice, resulted in disturbance in electrocardiograms in the mongoose, which
      returned to normal after several hours. Sarafotoxin-b failed to induce
      contraction of mongoose aortal preparations. Endothelin-1, which was demonstrated
      in tissue extracts of the mongoose by immunological methods, induced contraction
      of the isolated mongoose aorta. This contraction, however, was greatly reduced
      when endothelin-1 was applied on top of sarafotoxin-b. Binding studies revealed
      endothelin/sarafotoxin-specific binding sites in brain and cardiovascular
      preparations of the mongoose. It is suggested that some structural features of
      endothelin/sarafotoxin receptors in the mongoose enable them to differentiate
      between the two peptides.

PMID- 9278975
TI  - Changes to biological activity following acetylation of dendrotoxin I from
      Dendroaspis polylepis (black mamba).
AB  - The potassium channel blocker dendrotoxin I was acetylated with acetic anhydride.
      Mono-acetyl derivatives of all seven lysine residues (N-terminus blocked) and a
      di-derivative were isolated by chromatography on the cation-exchanger Bio-Rex 70
      and reversed-phase high-performance liquid chromatography. The derivative acetyl
      Lys 29 and the di-derivative of Tyr 24 and Lys 28 had more than 1000 times lower
      affinity than the native toxin as determined by inhibition of the 125I
      dendrotoxin binding to synaptosomal membranes from rat brain. Lys 29 is part of
      the triplet Lys-Lys-Lys (28-30) which also occurs in the homologous alpha
      dendrotoxin where the triplet is not in the functional site, as shown by site
      directed mutagenesis. Acetylation of Lys 29 may have produced large structural
      perturbations that inactivated the toxin. Acetylation of Lys 28 alone had little
      effect, but the toxin became almost inactive when both Lys 28 and Tyr 24 were
      modified. Ten experiments were conducted under similar conditions, but a
      derivative of Tyr 24 was obtained only three times. In these cases the toxin
      apparently had a different structure, with Tyr 24 accessible to the reagent. This
      may depend on freeze-drying, which can alter the structure of proteins. The third
      derivative with low activity was acetyl-Lys 5, with affinity decreased 20-fold.
      Lys 5 has a protruding side-chain that does not interact with any other group in
      the toxin molecule. Therefore, Lys 5 is probably part of the functional site for
      dendrotoxin's binding to the voltage-dependent K+ channels.

PMID- 9278976
TI  - Effects of a homoanatoxin-a-containing extract from Oscillatoria formosa
      (Cyanophyceae/cyanobacteria) on neuromuscular transmission.
AB  - Experimental investigations were carried out with cultured and lyophilized
      material of the toxigenic strain Oscillatoria NIVA-CYA 92. This organism is
      classified as Phormidium formosum (Boryex Gom.) Anagnet kom. Aqueous extracts of
      the algal material, containing the bioactive secondary amine alkaloid 2-(propan-1
      oxo-1-yl)-9-azabicyclo(4,2,1)non-2ene (homoanatoxin-a) in an amount of 2.57
      micrograms/mg lyophilized material, were tested for acute in vivo toxicity in
      mice, and for toxicity on neuromuscular transmission by means of
      electrophysiological methods on the isolated phrenic-nerve hemidiaphragm from rat
      and in the frog rectus abdominis assay. Acute toxic effects in mice were observed
      by i.p. and oral (by gavage) administration. Lethal doses were in the range 112
      225 and 1125-2250 mg of freeze-dried algal material per kg body weight (i.e. 288
      578 and 2890-5780 micrograms homoanatoxin-a/ kg body weight), respectively. The
      nerve-initiated muscle contractions in the rat diaphragm were blocked by about
      0.125 mg cyanophyte material per ml bath solution (i.e. 0.32 microgram
      homoanatoxin-a/ml or 1.8 microM), but muscle contractions, although slightly
      reduced, could still be elicited by direct electrical stimulation of the muscle.
      The compound action potentials recorded from the main phrenic-nerve trunk were
      not affected. An additive blocking effect on partly curarized preparations was
      observed and cholinesterase inhibition by physostigmine (eserine) transiently
      augmented the muscle twitch contraction in preparations partly blocked by the
      extract. Intracellular recordings from single muscle fibers of homoanatoxin-a
      treated rat hemidiaphragm disclosed a partial depolarization and a decrease in
      the endplate potential to subthreshold level simultaneously with a decrease and
      then complete disappearance of the miniature endplate potentials. The
      neuromuscular transmission block was reversed by washing. The extract produced
      muscle contractions in the frog rectus abdominis assay. Homoanatoxin-a in the
      algal material was readily absorbed from the gastrointestinal tract in mice.
      Blockade of the neuromuscular transmission of the respiratory muscle may partly
      explain the acute toxic effects observed in mice. Thus, the main target of the
      homoanatoxin-a action at the mammalian neuromuscular junction was traced to the
      postsynaptic nicotinic acetylcholine receptor channel complex, where it reduced
      the sensitivity to the transmitter substance.

PMID- 9278977
TI  - Pathogenesis of hemorrhage induced by proteinase H from eastern diamondback
      rattlesnake (Crotalus adamanteus) venom.
AB  - The pathogenesis of hemorrhage of a purified hemorrhagic toxin, proteinase H from
      Crotalus adamanteus venom, was studied. Female, white CD-1 mice were injected
      intramuscularly with sublethal doses of the hemorrhagic toxin and tissue samples
      were obtained at 10 min, 1, 3 and 24 hr following injection. Severe local
      hemorrhage was observed grossly within 10 min. Hemorrhage was observed in the
      connective tissue of skeletal muscle and within adjacent adipose tissue. Many
      larger vessels were congested with erythrocytes and platelets. By 3 hr
      inflammatory cell infiltration was observed and necrosis of some muscle cells was
      evident. Transmission electron microscopy showed that the capillary endothelium
      was ruptured, leading to hemorrhage per rhexis. Capillary basal laminae were
      disorganized and often wholly or partially absent.

PMID- 9278978
TI  - Systemic hemorrhage induced by proteinase H from Crotalus adamanteus (eastern
      diamondback rattlesnake) venom.
AB  - The systemic effects of a purified hemorrhagic toxin, proteinase H, from Crotalus
      adamanteus venom, were studied. Female, white CD-1 mice were injected
      intravenously with proteinase H and tissue samples were obtained at 1, 3 and 24
      hr after injection. Hemorrhage was observed grossly within 1 hr in several
      internal organs including the stomach and small intestine, the heart and the
      lungs. Surface discolorations thought to be petechial hemorrhages were observed
      in the kidneys. The livers of treated animals were visibly swollen and darkened
      and lobules were accentuated. Tissue samples were taken from the stomach,
      duodenum, heart, lungs, liver and kidneys and prepared for observation by light
      and electron microscopy. Frank hemorrhage was observed by light microscopy in the
      walls of the stomach and duodenum, in the myocardium and in the lungs. Pulmonary
      hemorrhage was severe, with involvement of nearly all of the pulmonary tissue
      within 3 hr. A1 doses of 5 micrograms/g, hepatic degeneration was observed by 3
      hr. Renal glomeruli were noticeably swollen and the lumena of the proximal
      convoluted tubules indistinct. Closer examination by electron microscopy revealed
      that the endothelial cells comprising the fenestrated glomerular capillaries
      remained intact but signs of degeneration (i.e. cytoplasmic swelling and
      mitochondrial swelling) were observed. Proteinase H induces systemic hemorrhage
      in the heart, lungs, stomach and small intestine, renal glomerulonephropathy and
      hepatic degeneration.

PMID- 9278979
TI  - Acanthoxin, a toxic phospholipase A2 from the venom of the common death adder
      (Acanthophis antarcticus).
AB  - This is the first report of a phospholipase A2 (PLA2) from the venom of the
      common death adder, Acanthophis antarcticus. Acanthoxin is a basic, monomeric
      PLA2 of mol. wt 13,000, consistent with the weight of neurotoxic PLA2s from other
      Australian elapids. However, preliminary ultracentrifugation experimentation has
      shown that it is able to undergo concentration-dependent aggregation to form
      dimers. It has a relatively high degree of enzymatic activity (23.93 +/- 1.18
      mumoles of phospholipid hydrolysed/min/mg protein), but a low level of toxicity
      (3.2 mg/kg, s.c.). Acanthoxin is known to exist as two isoforms (A1 and A2), both
      of which show a high degree of homology with numerous elapid PLA2 neurotoxins, in
      particular pseudexin A from the red-bellied black snake (Pseudechis
      porphyriacus).

PMID- 9278980
TI  - Toxicity and toxic components of two xanthid crabs, Atergatis floridus and
      Demania reynaudi, in Taiwan.
AB  - Paralytic toxicity was detected by tetrodotoxin bioassay in eight specimens of
      Atergatis floridus and seven specimens of Demania reynaudi, collected from Taiwan
      in 1994. The toxicity of crab specimens was 161 +/- 115 (mean +/- S.D.) mouse
      units (MU) for A. floridus and 640 +/- 273 MU for D. reynaudi. The respective
      toxins were partially purified from specimens of A. floridus and D. reynaudi by
      ultrafiltration using a Diaflo YM-1 membrane, followed by chromatography on a Bio
      Gel P-2 column. Electrophoresis, thin-layer chromatography, high-performance
      liquid chromatography, ultraviolet spectrum and gas chromatography-mass
      spectrometry indicated that the toxin of A. floridus was mainly composed of
      tetrodotoxin (85%), along with minor gonyautoxin 1-4 (15%), and the toxin of D.
      reynaudi was mainly composed of tetrodotoxin (88%), along with minor gonyautoxin
      2-4 and neosaxitoxin (12%).

PMID- 9278981
TI  - Interaction between botulinum neurotoxin type A and ganglioside: ganglioside
      inactivates the neurotoxin and quenches its tryptophan fluorescence.
AB  - This study found that ganglioside quenched the tryptophan fluorescence of
      botulinum neurotoxin type A (BoNT A), accompanied by the inactivation of the
      toxin under low ionic strength conditions. This finding suggests that the
      ganglioside-binding site of BoNT A contains tryptophan residues. The quantum
      yield (a conformation parameter) in BoNT A under high ionic strength conditions
      differed from that under low ionic strength. This observation indicates that high
      ionic strength may alter the conformation of BoNT A, resulting in failure of the
      interaction between BoNT A and ganglioside.

PMID- 9278983
TI  - Recognition of a 31,000 molecular weight protein synthesized by the mussel
      Mytilus galloprovincialis Lmk. during Dinophysis spp. algal bloom in the Gulf of
      Trieste (upper Adriatic Sea).
AB  - During Dinophysis spp. bloom, a histological alteration in the digestive gland of
      Mytilus galloprovincialis Lmk. occurs. Electrophoretic analysis of the water
      soluble proteins of the hepatopancreas showed the presence of a low mol. wt
      protein, which appeared after the ingestion of algae by mussels. The probable
      relationship between the toxicity of Dinophysis and the synthesis of the new
      protein by mussels prompted us to produce a monoclonal antibody against this
      protein because it should be useful for the identification of mussel toxicity.

PMID- 9278982
TI  - Occurrence of paralytic shellfish poisons in Thai freshwater puffers.
AB  - Screening tests were carried out on the toxicity of freshwater puffers Tetraodon
      leiurus complex and Tetraodon suvatii collected from Udonthani province, north
      eastern Thailand. Toxicity was highest in the liver and varied according to the
      location and season of fish catch. Fish which were reared in tap water for 3
      months reduced the toxicity substantially. Partial purification was achieved by
      an ultrafiltration technique. Toxin components were consequently identified by
      high-performance liquid chromatography. It was found that toxins separated from
      the eggs, liver, skin and muscle of these puffers were composed of saxitoxin,
      neosaxitoxin and decarbamoylsaxitoxin.

PMID- 9278985
TI  - Bibliography of toxinology.

PMID- 9278984
TI  - Toxic properties of Beauveria pigments on erythrocyte membranes.
AB  - The Beauveria pigments, tenellin, bassianin and oosporein, all inhibited total
      erythrocyte membrane ATPase activity in a dose-dependent manner by as much as 50%
      at 200 micrograms/ml. These pigments inhibited Ca(2+)-ATPases to a greater extent
      than Na+/K(+)-ATPase activity. The ATPase inhibitory activity for these pigments
      was not specific but was probably a consequence of membrane disruption, since
      pigments all caused alterations in erythrocyte morphology and promoted varying
      degrees of cell lysis.

PMID- 9278986
TI  - Mental health utilization in women with symptoms of depression.
AB  - This paper examines the help-seeking process of mental health services in women
      with high depressive symptoms. The data are based on an island wide probabilistic
      sample (n = 1,062) of 18- to 64-year-old women living in low socioeconomic areas
      in Puerto Rico. Symptoms of depression were measured by the Center for
      Epidemiological Studies Depression Scale (CES-D). Results show that one out of
      three women living in poor residential areas report high depressive symptoms. Of
      these women with high depressive symptoms, only 12% seek help from a mental
      health specialist and 14.5% from a general health care provider to deal with
      their emotional problems. Some factors related to the use of mental health
      services are: presence of an occupational disability, head of household status,
      having private insurance, and having a regular source of care. These data suggest
      that women underutilize mental health services and overutilize physical health
      services to deal with their emotional problems. The lack of recognition of
      emotional problems by these women may explain the low utilization of mental
      health services.

PMID- 9278987
TI  - Talking about health and health care: experiences and perspectives of Latina
      women in a farmworking community.

PMID- 9278988
TI  - Women and the heterosexual transmission of HIV: risks and prevention strategies.
AB  - Heterosexual intercourse has become a significant means of HIV transmission, even
      in countries where this was previously not the case. Consequently the promotion
      of safer sexual practices for heterosexual women and men is of major public
      health importance. We examine the risks to women of contracting HIV through
      heterosexual sex, and critically discuss the most commonly recommended strategies
      for safer sex for heterosexuals. We conclude that all safer sex strategies have
      limitations, and therefore a wide range of options should be promoted.

PMID- 9278990
TI  - Two opposite effects of ATP on the apparent sensitivity of the cGMP-gated channel
      of the carp retinal cone.
AB  - Effects of ATP on the activity of cGMP-gated channels from carp cone
      photoreceptors were studied. In 29% of the patches examined (N = 45), ATP (1 mM)
      enhanced a current evoked by cGMP (20 microM, up to about 100%), in 33%. ATP
      suppressed it by up to about 90%, and in the remaining 38%, ATP had no effect.
      ATP showed similar effects on a current evoked by 8-bromoguanosine 3',5'-cyclic
      monophosphate (2 microM, enhancing in 42% of the patches, suppressing in 25%, no
      effect in 33%, N = 12), suggesting that the effects were not through modulation
      of the phosphodiesterase. Both of the effects, enhancement and suppression, were
      produced by a change in apparent affinity for cGMP, since (1) the maximum current
      evoked by cGMP of the saturating concentration (> or = 1 mM) was not affected,
      and (2) the K1/2 value decreased by approximately 45% (N = 2) or increased by
      approximately 25% (N = 2). A lower pH (approximately 6) facilitated the enhancing
      effect. ATP-gamma-S (1 mM) showed a suppressing effect in 80% of the patches and
      no effect in 20% of the patches (N = 10). However, ATP-gamma-S did not show an
      enhancing effect. Thus, ATP had two opposite effects through different mechanisms
      on the apparent sensitivity of the channel to cGMP; increasing and decreasing.

PMID- 9278989
TI  - Condom use with main partners by sterilized and non-sterilized women.
AB  - This study examined condom use with main partners by surgically sterilized and
      non-sterilized women at risk for HIV infection. Data were obtained from 379
      African American women residing in low-income urban communities. Sterilized women
      were one-fifth as likely as non-sterilized women to use condoms. Multivariate
      logistic regression indicated that for both groups of women, higher perceived
      benefits of condom use for disease prevention were associated with condom use. In
      addition, younger age, self-efficacy for condom use, peer support for condom use,
      and whether condoms were ever used for pregnancy prevention were associated with
      condom use among non-sterilized women. Results of this study indicate the role of
      fertility status in condom use and the value of developing targeted prevention
      programs that reach women at high risk for HIV infection. Risk reduction programs
      need to emphasize the role of condoms in disease prevention and address attitudes
      towards condom use.

PMID- 9278991
TI  - A 221-bp fragment of the mouse opsin promoter directs expression specifically to
      the rod photoreceptors of transgenic mice.
AB  - Mutations in the human rod opsin gene have been shown to segregate with autosomal
      dominant retinitis pigmentosa (ADRP) and photoreceptor degeneration in transgenic
      mice. While these degenerations are characterized by the primary degeneration of
      rods, cones eventually die as well. To determine whether this subsequent cone
      degeneration is the result of expression of mutant rod opsin in the cones, the
      retinal cell-type specificity of a 221-bp fragment of the mouse rod opsin
      promoter was evaluated. Two transgenic mouse lines generated by injecting a
      fusion gene comprised of a 221-bp fragment of the mouse rod opsin promoter and
      the simian virus 40 large tumor antigen gene (Tag) were examined. The expression
      of Tag causes photoreceptor cell degeneration in members of both transgenic
      lines. However, the two lines differed with respect to the level of Tag
      expression and the rate and extent of photoreceptor cell degeneration.
      Immunocytochemical localization of opsin and Tag in surviving photoreceptor cells
      was determined and the results were confirmed by reverse transcriptase polymerase
      chain reaction (RT-PCR). Rod- and cone-mediated function was evaluated by
      electroretinography (ERG). In the higher Tag-expressing transgenic line only one
      row of nuclei remained in the outer nuclear layer at postnatal day (P) 150. While
      these nuclei showed no antigenicity for rod opsin or Tag, they did stain with an
      antibody that reacts with both rod and cone S-antigens (arrestins), indicating
      that these cells were surviving photoreceptor nuclei. Positive staining with
      peanut agglutinin, which uniquely decorates matrix domains surrounding cones in
      the normal retina, confirmed that the surviving photoreceptor nuclei were of cone
      origin. RT-PCR substantiated the results from immunostaining; amplification
      product was obtained using blue cone opsin transcripts but not from either Tag or
      rod opsin transcripts. The second transgenic mouse line exhibited a much slower
      photoreceptor cell death that was associated with low levels of Tag transgene
      transcript. At P120, approximately 50% of photoreceptors remained and an
      approximately 45% reduction in the rod ERG a-wave was observed. Cone-mediated
      ERGs, however, were normal. The results demonstrate the rod-specific expression
      of Tag as directed by the 221-bp fragment of the mouse rod opsin promoter and
      suggest that the cone degeneration in ADRP or transgenic mice associated with
      mutations in the rod opsin gene is a secondary effect of rod degeneration.

PMID- 9278992
TI  - Functional consequences of oncogene-induced horizontal cell degeneration in the
      retinas of transgenic mice.
AB  - Visual function was evaluated in transgenic mice expressing the simian virus 40
      early region under the control of the promoter for phenylethanolamine-N
      methyltransferase. These transgenic mice undergo a degeneration of the retinal
      horizontal cells and the outer plexiform layer. Electroretinograms (ERGs) were
      recorded under stimulus conditions chosen to elicit both receptoral and
      postreceptoral responses. The dark-adapted a-waves obtained from transgenic mice
      were not different from control recordings, indicating that the degenerative
      process does not interfere with function of the rod photoreceptors. In
      comparison, the ERG b-wave was markedly reduced in transgenic mice under both
      dark- and light-adapted conditions. Reproducible visual evoked potentials (VEPs)
      were recorded from transgenic mice in response to both low luminance stimuli that
      isolate rod function, and to higher luminance stimuli, indicating that retinal
      activity is transmitted centrally to the visual cortex. However, VEPs were
      delayed at all stimulus luminances compared to controls. Analysis of luminance
      response functions suggests that the VEP delays could reflect the combination of
      a decrease in synaptic efficacy and an overall loss in visual sensitivity. These
      functional abnormalities correlate well with the anatomical abnormalities that
      have been previously observed in the transgenic retina (Hammang et al., 1993),
      namely a reduced number of synapses between photoreceptors and second-order
      neurons.

PMID- 9278993
TI  - Responses in ventral intraparietal area of awake macaque monkey to optic flow
      patterns corresponding to rotation of planes in depth can be explained by
      translation and expansion effects.
AB  - There is evidence that neurons in medial superior temporal area (MST) respond to
      rotation in depth of textured planes. MST neurons project to the ventral
      intraparietal area (VIP) and the question arises whether VIP neurons are
      responsive to rotation in depth as well. In the present study on awake monkeys,
      we have simulated movement of a flat board, covered with dots, by a computer. The
      two-dimensional images corresponded to the projection of structured planes
      rotating around a fronto-parallel axis. In the literature this stimulus is called
      fanning. Fanning effectively induced responses in VIP neurons. Most often the
      responses were nearly as strong as for translation, expansion/contraction, or
      rotation, indicating that there was no special sensitivity for rotation in depth.
      For neurons, sensitive to expansion, the response to fanning could often be
      explained by the positioning of the expanding part of the fanning stimulus over
      the area which was most responsive to expansion. For neurons which were direction
      selective to translation, the optimal direction of fanning was usually the same
      as the preferred direction for translation. It is concluded that VIP neurons may
      be sensitive to movement of structured planes but they are not specialized for
      the detection of such movement.

PMID- 9278994
TI  - Interlaminar connections of the superior colliculus in the tree shrew. III: The
      optic layer.
AB  - These experiments were designed to test the idea that the optic layer in the tree
      shrew, Tupaia belangeri, is functionally distinct and provides a link between the
      visuosensory superficial and the premotor intermediate layers of the superior
      colliculus. First, cells in the optic layer were intracellularly labeled with
      biocytin in living brain slices. Compared to cells in the adjacent lower part of
      the superficial gray layer, which have apical dendrites that ascend toward the
      tectal surface, optic layer cells have dendritic fields that are restricted for
      the most part to the optic layer itself. The differences in dendritic-field
      location imply that superficial gray and optic layer cells have different
      patterns of input. The axons of optic layer cells terminate densely within the
      optic layer and, in addition, project in a horizontally restricted fashion to the
      overlying superficial gray and subjacent intermediate gray layers. This pattern
      also is different from the predominantly descending interlaminar projections of
      lower superficial gray layer cells. Next, cells in the intermediate gray layer
      were labeled in order to examine the relationships between optic layer cells and
      these subjacent neurons that project from the superior colliculus to oculomotor
      centers of the brain stem. Neurons in the upper part of the intermediate gray
      layer send apical dendrites into the optic layer and therefore can receive
      signals from the superficial gray layer either directly, from descending axons of
      lower superficial gray layer cells, or indirectly, through intervening optic
      layer cells. In contrast, lower intermediate gray layer cells have more radiate
      dendritic fields that are restricted to the intermediate gray layer. Thus, these
      lower cells must depend on descending projections from optic or upper
      intermediate gray layer cells for signals from the superficial gray layer.
      Together, these results support the idea that the optic layer is a distinct
      lamina that provides a link between the superficial and intermediate gray layers.
      They also are consistent with the traditional view that descending
      intracollicular projections play a role in the selection of visual targets for
      saccades.

PMID- 9278995
TI  - The monoclonal antibody H386F labels microglia in the retinal nerve fiber layer
      of several mammals.
AB  - The antibody H386F revealed microglia in the retinae of several species: owl
      monkey, slow loris, galago, ferret, raccoon, and tree shrew. The shape, size, and
      density of labeled microglia were identical to those labeled by OX-42 and OX-41,
      two antibodies specific for microglia, in both galago and owl monkey. The labeled
      microglia varied little in retinal location. There was remarkably little
      variability in density, shape, number, and size of the labeled microglia between
      species. All labeled microglia were evenly distributed across, but restricted to,
      the nerve fiber layer. Possible reasons for this restriction in location are
      discussed.

PMID- 9278996
TI  - A gradient of basic fibroblast growth factor in rod photoreceptors in the normal
      human retina.
AB  - Retinitis pigmentosa (RP) is an inherited disease that causes primary
      degeneration of rod photoreceptors in the retina. Although the causal gene (e.g.
      rhodopsin) is thought to be expressed in all rods across the retina, the
      degeneration is typically nonuniform, with rods in the far periphery surviving
      significantly longer than those in the midperiphery and macula. Basic fibroblast
      growth factor (bFGF) is a putative survival factor for photoreceptors, and the
      characteristic regional pattern of rod cell survival in RP suggested that bFGF
      might be distributed nonuniformly in the human retina. We performed double-label
      immunocytochemistry on 15 normal human retinas, using anti-bFGF and other
      antibody markers for retinal neurons and glia. Immunoreactivity for bFGF was
      consistently absent from cones but was present in rods, populations of cone
      bipolar and amacrine cells, Muller glial cells, and astrocytes. In the macula,
      the percentage of bFGF-reactive rods was very low (approximately 0.5%) but it
      increased in a central to peripheral gradient, accounting for up to approximately
      88% of the rods in the far periphery. These findings suggest that a central to
      peripheral gradient of rod bFGF is present in normal human retina and may
      influence the pattern of photoreceptor degeneration in RP. The absence of bFGF in
      cones and the low number of bFGF-positive rods in the macula may correlate with
      the vulnerability of these cells in RP, age-related macular degeneration, and
      other retinal diseases.

PMID- 9278997
TI  - Pattern of ocular dominance columns and cytochrome oxidase activity in a macaque
      monkey with naturally occurring anisometropic amblyopia.
AB  - Unilateral eyelid suture, a model for amblyopia induced by congenital cataract,
      produces shrinkage of the deprived eye's ocular dominance columns in the striate
      cortex. Loss of geniculocortical projections are thought to account for the poor
      vision in the amblyopic eye. It is uncertain whether ocular dominance columns
      become shrunken in other forms of amblyopia. We examined the striate cortex in a
      pigtailed macaque with natural anisometropia discovered at age 5 months.
      Amblyopia in the left eye was documented at 1 year by behavioral testing. At age
      6 years, the left eye was injected with [3H]proline and the striate cortex was
      processed for autoradiography and cytochrome oxidase (CO). The ocular dominance
      columns in layer IVc labelled with [3H]proline were normal. CO staining showed a
      novel pattern of thin dark bands in layer IV. These bands occupied the core zones
      at the center of the ocular dominance columns. Their appearance resulted from
      relative loss of CO activity along the borders of the ocular dominance columns,
      regions specialized for binocular processing. These findings indicate that not
      all forms of amblyopia are accompanied by shrinkage of ocular dominance columns.
      The unusual pattern of CO staining in layer IVc reflected a subtle alteration in
      metabolic activity which may have resulted from impairment of binocular function
      in anisometropic amblyopia.

PMID- 9278998
TI  - The distribution and morphology of LGN K pathway axons within the layers and CO
      blobs of owl monkey V1.
AB  - The lateral geniculate nucleus (LGN) of primates contains three classes of relay
      cells, the magnocellular (M), parvocellular (P), and koniocellular (K) cells. At
      present, very little is known about either the structure or function of the K
      relay cells in New or Old World monkeys (simian primates). In monkeys, K cells
      are located between the main LGN layers and adjacent to the optic tract. For
      convenience, these intercalated cell layers are numbered K1-K4 starting closest
      to the optic tract with K1. The objective of this study was to examine the
      details of K axon morphology in the primary visual cortex (V1) of owl monkeys and
      to determine if different K layers give rise to distinct axon types. For this
      purpose, injections of WGA-HRP or PHA-L were made into specific K LGN layers and
      the distribution and morphology of the resulting labeled axons were analyzed.
      Injections of fluorescent tracers also were made within the superficial layers of
      V1 to further document connections via analysis of the patterns of retrogradely
      labeled cells in the LGN. Our main finding is that K axons in owl monkeys
      terminate as delicate focused arbors within single cytochrome oxidase (CO) blob
      columns in cortical layer III and within cortical layer I. Overall, the
      morphology of the K axons in these monkeys is quite similar to what we described
      previously for K geniculocortical axons in the distantly related bush baby
      (prosimian primate), suggesting that the basic features of this pathway are
      common to all primates. Our results also provide evidence that the axon arbors
      from different K layers are morphologically distinct; axons from LGN layer K1
      project mainly to cortical layer I, while axons from LGN layer K3 chiefly
      terminate in cortical layer III. Taken together, these results imply that the
      basic features of axons within the K pathway are conserved across primates, and
      that the K axons from different K layers are likely to differ in function based
      upon their different morphologies.

PMID- 9278999
TI  - Tyrosine hydroxylase expression in the Cebus monkey retina.
AB  - Tyrosine hydroxylase (TH) expression was used as a marker to study the
      dopaminergic cells in the Cebus monkey retina. Two types of dopaminergic cells
      were identified by cell body size and location, level of arborization in the
      inner plexiform layer, and amount of immunolabeling. Type 1 cells displayed
      intense immunoreactivity and larger somata (12-24 microns) located in the inner
      nuclear layer or ganglion cell layer, whereas type 2 had smaller cell bodies (8
      14 microns) found either in the inner plexiform layer or ganglion cell layer and
      were more faintly labeled. Interplexiform cells were characterized as type 1
      dopaminergic cells. Immunoreactive axon-like processes were seen in the nerve
      fiber layer, and a net of fibers was visible in the foveal pit and in the extreme
      periphery of the retina. The population of TH+ cells was most numerous in the
      temporal superior quadrant and its density peaked at 1-2 mm from the fovea. Type
      1 TH+ cells were more numerous than type 2 cells at any eccentricity. Along the
      horizontal meridian, type 1 cell density was slightly higher in temporal (29
      cells/mm2) than in nasal (25 cells/mm2) retina, while type 2 cells had a
      homogeneous distribution (4.5 cells/mm2). Along the vertical meridian, type 1
      cells reached lower peak density (average 17.7 cells/mm2) in the inferior retina
      (central 4 mm), compared to the superior portion (23.7 cells/mm2). Type 2 cell
      density varied from 4.5 cells/mm2 in the superior region to 9.4 cells/mm2 in the
      inferior region. The spatial density of the two cell types varied approximately
      inversely while the total density of TH+ cells was virtually constant across the
      retina. No correlation between dopaminergic cells and rod distribution was found.
      However, we suggest that dopaminergic cells could have a role in mesopic and/or
      photopic vision in this species, since TH+ fibers are present in cone-dominated
      regions like the foveola and extreme nasal periphery.

PMID- 9279000
TI  - Immunocytochemical and histochemical localization of nitric oxide synthase in the
      turtle retina.
AB  - Recent interest in nitric oxide and its relationship to cGMP has produced many
      attempts to anatomically localize the enzyme synthesizing nitric oxide, nitric
      oxide synthase. In the retina, numerous previous studies have used the NADPH
      diaphorase enzyme activity of nitric oxide synthase as a histochemical method to
      localize nitric oxide synthase. However, all NADPH-diaphorase activity is not
      necessarily nitric oxide synthase, because several enzymes have similar
      biochemical activity. Additionally, various histochemical methods have been used
      to demonstrate NADPH-diaphorase activity, which makes comparisons between studies
      difficult. The purpose of this study was twofold. First, we wanted to examine the
      histochemical labeling of NADPH-diaphorase in the turtle retina to allow
      comparisons to previous studies. Second, we wanted to compare the histochemical
      localization of NADPH-diaphorase activity to the immunocytochemical localization
      of nitric oxide synthase in the turtle retina. Our histochemical localization of
      NADPH-diaphorase activity and our localization of nitric oxide synthase-like
      immunoreactivity in the turtle retina both produced similar results. Both the
      histochemistry and immunocytochemistry consistently labeled photoreceptor inner
      segments, at least three amacrine cell types, and processes in the inner
      plexiform layer. In optimized double-labeled preparations, all cells with NADPH
      diaphorase activity were also positive for nitric oxide synthase-like
      immunoreactivity, although some somata in the ganglion cell layer only had nitric
      oxide synthase-like immunoreactivity. The immunocytochemical localization of
      nitric oxide synthase in photoreceptors, amacrine cells, and putative ganglion
      cells indicates that nitric oxide may function at several levels of visual
      processing in the turtle retina.

PMID- 9279001
TI  - An analysis of the cross-correlation between ganglion cells in the retina of
      goldfish.
AB  - Neighboring ganglion cells in the retinae of vertebrates show cross-correlation
      between their impulse trains. Cross-correlation is found both in maintained
      discharges and during responses to visual stimulation. There has been speculation
      about the function of this statistical dependence, but little is known about its
      genesis. This study examines the statistics of the interimpulse intervals
      preceding and those following impulses that coincide with an impulse in the other
      train. Short intervals are rarer than expected preceding a coincidence,
      regardless of the form of the cross-correlation. Short intervals are more common
      than expected following a coincidence when the cross-correlation is positive, but
      rarer than expected following coincidences during negative cross-correlation.
      These results contradict the extant models for cross-correlation, but may be
      explained by the multiplicative combination of a variable common input and the
      variability within each cell. In addition, the lag (relative timing of coincident
      impulses in the two cells) is found to be related to the maintained discharge
      rates of the cells, implying that the lags may be explained without invoking
      specific delay circuits.

PMID- 9279002
TI  - An adaptive Reichardt detector model of motion adaptation in insects and mammals.
AB  - There are marked similarities in the adaptation to motion observed in wide-field
      directional neurons found in the mammalian nucleus of the optic tract and cells
      in the insect lobula plate. However, while the form and time scale of adaptation
      is comparable in the two systems, there is a difference in the directional
      properties of the effect. A model based on the Reichardt detector is proposed to
      describe adaptation in mammals and insects, with only minor modifications
      required to account for the differences in directionality. Temporal-frequency
      response functions of the neurons and the model are shifted laterally and
      compressed by motion adaptation. The lateral shift enhances dynamic range and
      differential motion sensitivity. The compression is not caused by fatigue, but is
      an intrinsic property of the adaptive process resulting from interdependence of
      temporal-frequency tuning and gain in the temporal filters of the motion
      detectors.

PMID- 9279003
TI  - Analysis of the distribution of glycine and GABA in amacrine cells of the
      developing rabbit retina: a comparison with the ontogeny of a functional GABA
      transport system in retinal neurons.
AB  - The objectives of this study were to (1) determine whether the glycinergic and
      GABAergic amacrine cells in the developing rabbit retina were neurochemically
      distinct at birth, (2) determine if the ratio of GABAergic to glycinergic
      amacrine cells was constant during development, (3) determine whether the
      capacity to take up a GABA analogue was restricted to GABAergic neurons, and (4)
      whether initiation of GABA transport into GABAergic neurons preceded the presence
      of a content of GABA in these neurons. We have used a novel strategy to
      immunolocalize a non-endogenous GABA analogue, gamma-vinyl GABA, which is taken
      up into neurons by a GABA transporter. Examination of serial semithin resin
      embedded sections of neonatal rabbit retinae that had been immunolabelled for
      glycine, GABA or gamma-vinyl GABA revealed that at 1 day postnatum, 60% of
      amacrine cells contain glycine but not GABA and did not accumulate gamma-vinyl
      GABA, which is similar to the percentage of glycinergic amacrine cells in the
      adult retina. The vast majority of the remaining amacrine cells contained GABA
      and many also transported gamma-vinyl GABA; however, a significant number of GABA
      containing cells failed to accumulate gamma-vinyl GABA suggesting that possession
      of a content of GABA did not have to be preceded by, or be concomitant with, the
      presence of a GABA transport system. By 10 days postnatum, over 99% of GABA
      containing amacrine cells also transported gamma-vinyl GABA indicating their
      functional maturity. Analysis of the horizontal cells revealed no evidence for
      uptake of gamma-vinyl GABA, but another GABA analogue, diaminobutyric acid, which
      is a substrate both for the neuron-associated GABA transporter and the glial GABA
      transporter, was accumulated into some horizontal cells at 21 days postnatum, a
      time point when these cells also contain endogenous GABA. We conclude that
      amacrine cells are committed to being GABAergic or glycinergic at, or prior to
      birth, and that in some amacrine cells, expression of a content of GABA may occur
      prior to the capacity to transport GABA. Conversely, in some ganglion cells
      transport of gamma-vinyl GABA may precede a content of GABA.

PMID- 9279004
TI  - Neuropeptide Y and enkephalin immunoreactivity in retinorecipient nuclei of the
      hamster pretectum and thalamus.
AB  - This investigation was stimulated by the historical confusion concerning the
      identity of certain pretectal nuclei and by large differences reported between
      species with respect to which nuclei receive retinal innervation. Subcortical
      visual nuclei were studied using immunohistochemistry to identify retinal
      projections labeled following intraocular injection of cholera toxin, b fragment.
      In addition, neuropeptide Y (NPY) or enkephalin (ENK) immunoreactive cells and
      fibers were also evaluated in the retinorecipient pretectal and thalamic areas.
      The results confirm the established view that the retina directly innervates the
      nucleus of the optic tract (NOT), posterior (PPT), and olivary pretectal (OPT)
      nuclei. However, the retina also innervates the hamster medial (MPT) and anterior
      (APT; dorsal division) pretectal nuclei, results not previously reported in
      rodents. A commissural pretectal area (CPT) sparsely innervated by retina is also
      described. The data show for the first time that the posterior limitans nucleus
      (PLi) receives a moderately dense, direct retinal input. The PLi does not project
      to the cortex and appears to be a pretectal, rather than thalamic, nucleus. All
      retinal projections are bilateral, although predominantly contralateral. The PLi
      contains a moderately dense plexus of NPY- and ENK-IR fibers and terminals.
      However, peptidergic fibers also traverse the ATP and connect with the
      dorsomedial pretectium. The OPT contains ENK- and NPY-IR neurons and fibers, but
      is specifically identifiable by a moderately dense plexus of ENK-IR terminals.
      Numerous ENK-IR neurons are found in the NOT and PPT. The latter also has
      moderate numbers of ENK-IR fibers and terminals, but few NPY-IR neurons or
      fibers. The MPT contains modest numbers of ENK-IR fibers. The APT has no NPY-IR
      neurons or terminals, but an occasional ENK-IR neuron is seen and there is sparse
      ENK-IR innervation. Peptidergic innervation of the visual nuclei does not appear
      to be derived from the retina. The results show a set of retinally innervated,
      contiguous nuclei extending from the thalamic ventrolateral geniculate nucleus
      dorsomedially to the midbrain CPT. These nuclei plus the superior colliculus
      comprise a dorsal "visual shell" embracing a central core of caudal thalamus and
      rostral midbrain.

PMID- 9279005
TI  - Dendritic development of retinal ganglion cells after prenatal intracranial
      infusion of tetrodotoxin.
AB  - The dendritic form of a cell may be established by many factors both intrinsic
      and environmental. Blockade of action potentials along the course of axons and in
      their postsynaptic targets dramatically alters the development of axonal
      morphology. The extent to which blockade of target cell activity retrogradely
      alters the dendritic morphology of the presynaptic cells is unknown. To determine
      whether the establishment of dendritic form by developing retinal ganglion cells
      depends on activity within their targets, the sodium channel blocker,
      tetrodotoxin (TTX), was administered via minipumps to the diencephalon of cat
      fetuses from embryonic day 43 (E43) to E57. At E57 retinae were removed and
      living retinal ganglion cells injected in vitro with Lucifer yellow to reveal
      their dendritic morphology. In the TTX-treated animals both alpha and beta types
      of retinal ganglion cells were present, as were putative gamma cells. Overall,
      the dendrites of retinal ganglion cells in TTX-treated animals appeared
      qualitatively and quantitatively similar to those of untreated animals. The only
      significant change in the TTX-treated cases was a small increase in the number of
      dendritic spines on the non-beta cells. These results indicate that the
      acquisition of basic dendritic form of developing ganglion cells is not
      influenced by the action potential activity within their targets, and that it is
      also independent of the terminal branching patterns of their axons.

PMID- 9279006
TI  - ON cone bipolar cells in rat express the metabotropic receptor mGluR6.
AB  - The rod bipolar cell and about five types of ON cone bipolar cells depolarize to
      light by employing a sign-reversing metabotropic glutamate receptor. Glutamate
      responses are similar in both rod bipolar and cone bipolar cells, but the
      receptor mediating this response (mGluR6) was so far demonstrated only in rod
      bipolar cells. To test if ON cone bipolar cells also express mGluR6, we
      immunoreacted rat retina with an antibody specific for mGluR6, and studied the
      staining from serial ultrathin sections. We demonstrate that mGluR6 is indeed
      expressed in the dendritic tips of cone bipolar cells, the majority of which
      receive a ribbon synapse, and thus probably are ON cone bipolar cells. We further
      show that half of the dendritic tips contacting the cones stain for mGluR6, thus
      implying that all ON cone bipolar cell types express mGluR6.

PMID- 9279007
TI  - Relationships between Muller cells and neurons in a primitive tetrapod, the
      Australian lungfish.
AB  - We recently proposed a model of cytogenesis which assumes that primitive
      ancestral mammals and premammalian vertebrates had a retinal composition that
      consisted of about seven neurons per Muller cell, comprising 1-2 cone
      photoreceptors, 1-2 rod photoreceptors, 2-3 bipolar cells, 1-2 amacrine cells,
      less than 1 ganglion cell, and less than 1 horizontal cell (Reichenbach &
      Robinson, 1995). The Australian lungfish (Neoceratodus forsteri) closely
      resembles the lobe-finned ancestors of land vertebrates, and has an extremely
      plesiomorphic nervous system. The present study, therefore, has examined the
      relative frequencies of retinal neurons and Muller cells (identified by
      immunolabelling for glutamine synthetase) in the lungfish retina. It was found
      that for each Muller cell there is an average of 1.9 cone photoreceptors, 1.7 rod
      photoreceptors, 3.1 amacrine/bipolar/horizontal cells, and 0.6 ganglion cells;
      amounting to a ratio of 7.3 neurons per Muller cell. These results support our
      conjecture that the sequence of cytogenesis in mammals is constrained by a
      developmental program that predates the evolution of mammals. The study also
      provides the first detailed morphological descriptions of lungfish Muller cells
      and their relationship with adjacent neurons. It was found that individual Muller
      cells in lungfish have a volume (more than 12,000 microns3) that is an order of
      magnitude higher than in mammals, yet the proportion of total retinal volume
      occupied by these cells (20%) is very similar.

PMID- 9279008
TI  - Genetic substructuring as a result of barriers to gene flow in urban Rana
      temporaria (common frog) populations: implications for biodiversity conservation.
AB  - The ability to maintain small populations in quasi-natural settings is an issue
      of considerable importance in biodiversity conservation. The genetic structure of
      urban common frog (Rana temporaria) populations was determined by allozyme
      electrophoresis and used to evaluate the effects of restricted intersite
      migration. Despite the lack of any absolute barrier to movement between ponds,
      substantial genetic differentiation was found between sites separated by an
      average of only 2.3 km. Genetic distances between these town ponds correlated
      positively with geographical distances and were almost twice as great as those
      found between rural sites separated by an average of 41 km. Measures of genetic
      diversity and fitness were always lowest in the town, where the degree of
      subpopulation differentiation (FST = 0.388) was high. Population decline was not
      evident in the town, but molecular and fitness data indicated the presence of
      genetic drift and inbreeding depression. The long-term survival of artificially
      restricted populations, particularly of relatively sedentary species, may require
      molecular monitoring, if genetic diversity is not to be lost by chance when
      facets of the species niche prove to be poorly understood.

PMID- 9279009
TI  - Chromosomal distribution of the 412 retrotransposon in natural populations of
      Drosophila simulans.
AB  - The insertion site localization of the 412 retrotransposable element was analysed
      by in situ hybridization to the polytene chromosomes of 57 individual genomes
      from 25 natural populations of Drosophila simulans. The 412 insertion sites along
      the chromosomes show a tendency to aggregate in the distal and proximal ends of
      the 2R arm, and in several local regions along the 3R arm. The distribution of
      the 412 insertion sites, weighted by DNA content, along the chromosome arms
      reveals an overall tendency for the site number to increase from the middle of
      the arm to the base and tip, with a decrease at the tips, especially pronounced
      for the X chromosome. Such a distribution differs slightly from that of D.
      melanogaster, which globally shows an increase of the 412 site number from base
      to tip of the chromosome arms, indicating differing behaviour of the 412 element
      in the two species. These results are discussed in connection with the
      recombination rate along the chromosome arms.

PMID- 9279010
TI  - Genetic variation at marker loci and in quantitative traits in natural
      populations of Arabidopsis thaliana.
AB  - Genetic variation was studied in quantitative traits and molecular markers in six
      natural Scandinavian populations of Arabidopsis thaliana. Only two of the
      populations had several molecular marker haplotypes and significant between
      family variance components in quantitative traits. There was no genetic variation
      in the other four populations. The differentiation between the populations was
      high in both molecular markers and quantitative traits, with FST estimates of
      above 0.60 in almost all traits. The patterns of variation of the neutral markers
      and morphological and phenological traits were consistent in all the analyses, as
      opposed to what has been found in predominantly outcrossing species. The general
      picture of the level and distribution of genetic variance agrees with the
      information from other predominantly inbreeding species.

PMID- 9279011
TI  - Novosibirsk revisited 24 years on: chromosome polymorphism in the Novosibirsk
      population of the common shrew Sorex araneus L.
AB  - A Robertsonian fusion polymorphism in the common shrew (Sorex araneus L.), first
      described in Academgorodok near Novosibirsk (western Siberia) in 1970-72, was re
      examined in 1994-95. The polymorphism in the 1970s involved chromosome arm
      combinations go, jl, mp and qr, i.e. each of these combinations was present in
      both a metacentric and a twin-acrocentric state in the population at that time.
      The twin-acrocentric morph for go occurred at low frequency in 1970-72 and was
      not observed in 1994-95. The polymorphism for arm combinations jl, mp and qr was
      still observed in 1994-95 and there was no significant difference in
      metacentric/twin-acrocentric frequencies compared with the previous sample. This
      is the third well-documented example in which the chromosome polymorphism in the
      common shrew has been found to be unchanged over a period of 20+ years. Although
      the polymorphism for qr may be associated with a chromosomal hybrid zone with a
      cline centre 200 km away, there is no definitive explanation for the other
      polymorphisms.

PMID- 9279012
TI  - Mitochondrial DNA variation in the scallop Pecten maximus (L.) assessed by a PCR
      RFLP method.
AB  - Two PCR-RFLP mitochondrial DNA (mtDNA) markers were developed through the cloning
      and sequencing of mtDNA from the scallop Pecten maximus, and were used to study
      genetic differentiation off UK and Atlantic coast populations of this species.
      Although no distinct pattern of mtDNA haplotype frequencies was apparent and no
      diagnostic haplotypes were identified for any population, sequence divergence
      data provided convincing evidence that a P. maximus sample taken from Mulroy Bay,
      Eire, a semi-enclosed sea lough, was genetically differentiated form all other
      samples. However, this could not be unequivocally attributed to a restriction in
      gene flow, as the sample consisted of an ongrown single spatfall, which may not
      have been representative of the wild population. Despite the inability to
      separate populations on the basis of haplotype frequency, it was noteworthy that
      the frequency pattern of the commonest haplotype varied between sampling sites in
      a manner similar to that of allozyme allele frequencies in Aequipecten
      opercularis, a scallop species with a similar distribution and life history, for
      which there is evidence of population subdivision. Pecten maximus from St. Brieuc
      Bay, reasoned to be a self-recruiting population from reproductive and
      physiological evidence, could not be separated from other populations using mtDNA
      markers. Further investigation of this population with alternative markers is
      warranted.

PMID- 9279013
TI  - QTL analysis of seed dormancy in Arabidopsis using recombinant inbred lines and
      MQM mapping.
AB  - The genetic differences for seed germination between two commonly used
      Arabidopsis thaliana ecotypes Ler and Col, both showing a low level of seed
      dormancy, were investigated. The analysis was performed with 98 recombinant
      inbred lines (RILs) derived from the cross between the two ecotypes, and these
      lines had previously been analysed for molecular marker composition by Lister and
      Dean (Norwich, UK). The analysis of germination was performed on seeds grown in
      three different maternal environments and each seed batch was tested in three
      different germination environments: in light, in darkness and in the presence of
      the gibberellin inhibitor paclobutrazol. Fourteen loci were identified using the
      multiple-QTL-model (MQM) procedure for mapping quantitative trait loci. At nine
      loci no significant interaction between the detection of the locus and
      environmental factors could be detected. However, three other distinct loci
      controlling the germination behaviour in the presence of the gibberellin
      inhibitor paclobutrazol had a much lower or no effect when germination was tested
      in water either in light or darkness. Two other loci affecting germination in
      darkness and/or light had practically no effect on germination in the presence of
      paclobutrazol.

PMID- 9279014
TI  - Chiasma interference is blind to centromeres.
AB  - It has long been assumed, since the early works of Mather, that the centromere
      plays a central role in chiasma position determination, so much so that in all
      sequential models chiasma determination was supposed to start or finish at this
      point. More specifically, it has been assumed that the centromere acts as a
      barrier to the transmission of interference, so that a chiasma in the vicinity of
      a centromere would not affect the probability of chiasma formation across at this
      point. Some statistical analyses seemed to ratify this supposition. However, a
      reassessment of the literature led us to the conclusion that the statistical
      analyses that were not flawed were consistent in showing that interference may
      act across the centromere. Using large sets of chiasma data from the grasshoppers
      Leptysma argentina and Chorthippus brunneus and applying statistical approaches
      that involved either the calculation of coincidence or correlating the distances
      between the centromere and the nearest chiasma in either arm, it is concluded: 1.
      that interference acts across the centromere; 2. that the action of interference
      is not changed by the presence of an intervening centromere.

PMID- 9279017
TI  - Corneal lens secretion in newly emerged Drosophila melanogaster examined by
      electron microscope autoradiography.
AB  - Drosophila corneal lens secretion was studied by electron microscope
      autoradiography of [3H]amino acids (leucine, lysine, phenylalanine, proline and
      tyrosine) and [3H]sugars (glucosamine and mannose) in newly emerged flies.
      Ommatidial lenses were homogeneously labelled with both tracers at low levels,
      suggesting that lens materials turn over continuously after lens formation is
      completed. In contrast, ocellar lenses were heavily labelled, indicating that
      deposition of ocellar lens cuticle is still active at this stage. [3H]amino acids
      and [3H]sugars were deposited in distinct patterns in ocelli. Although over 90%
      of [3H] sugars remained, even after 3 h after application, within 1 micron of the
      apices of corneagenous cells associated with lens bases, [3H]amino acids
      distributed diffusely. There was an obvious gradient of [3H]sugars from center to
      periphery of the lens base, suggesting that structure of the corneal lens in
      dorsal ocelli is determined by spatially regulated secretion of chitin by
      corneagenous cells.

PMID- 9279016
TI  - Isolated collagen IV retains the potential to form an 18-nm sided polygonal
      meshwork of the lamina densa.
AB  - Polygonal meshworks were revealed in the aggregates reconstituted from isolated
      collagen IV as well as in the lamina densa of mouse pancreas by the quick
      freezing and deep-etching technique. Collagen IV solution with acetic acid from
      the bovine lens capsules and that isolated from the pepsin-solubilized fraction
      of human placenta reconstituted polygonal meshworks, which were dimensionally
      similar to the meshwork seen in the lamina densa of mouse pancreas. The average
      lengths between branching points in the lamina densa, and the meshworks of
      collagen IV derived from the bovine lens capsules and from the human placenta
      were 20.1 +/- 7.7 nm (mode = 18 nm), 21.6 +/- 11.3 nm (mode = 14 nm), and 21.6 +/
      9.0 nm (mode = 18 nm), respectively. These observations suggest that collagen IV
      can, in the absence of other macromolecules including laminins, comprise a
      skeletal meshwork similar in dimensions to that of the lamina densa.

PMID- 9279018
TI  - Ultrastructural observations on the tendon sheath of the rat tail.
AB  - The ultrastructure of the tendon sheath of the rat tail was examined with
      scanning and transmission electron microscopes. The tendon sheath was divided
      into three layers: the visceral, parietal and fibrous layers. By scanning
      electron microscopy, the longitudinal shallow ridges approximately 7 microns wide
      were seen on the surface of the visceral layer. On the other hand, the spiral
      ridges approximately 20 microns wide running at an angle of 35 degrees to the
      longitudinal axis were exposed clearly on the inner surface of the parietal
      layer. Blood capillary networks were also observed on the surface of the parietal
      layer, especially in the specimens treated with HCl. The fibrous layer of the
      tendon sheath was characterized by a large number of collagen fibers in a woven
      arrangement. The inner surface of the fibrous layer showed spiral ridges similar
      to that of the parietal layer, suggesting that the ridges of parietal and fibrous
      layers were concerned with the arrangement of collagen fibers in the innermost
      region of the fibrous layer.

PMID- 9279019
TI  - Skeletal muscle fibre ends of the frog as revealed by scanning electron
      microscopy.
AB  - Muscle fibre ends at myotendinous junctions were examined by scanning electron
      microscopy after removal of tendon connective tissues by HCl-hydrolysis in the
      fourth extensor digitorum longus muscle and the extraocular muscle of the frog.
      The fibre ends in both muscles were characterized by the presence of small pit
      like and short slit-like invaginations. The fibre ends in the extensor digitorum
      longus muscle took a spongy appearance with a great number of invaginations,
      while those on the extraocular muscle consisted of a number of pits and short
      slits arranged linearly toward the fibre tip. These findings confirm that muscle
      fibre ends in the frog consist of sarcolemmal invaginations to increase the
      surface area where collagen fibrils attach to the basal laminae of muscle fibres.
      The difference of the surface specializations between two kinds of muscle fibres
      may intimately reflect the functional properties of the muscle.

PMID- 9279020
TI  - Existence of a muscle spindle on the posterior cricoarytenoid muscle of the
      guinea pig.
AB  - We examined a muscle spindle in the posterior cricoarytenoid muscle of the adult
      guinea pig. The spindle capsule contained three intrafusal muscle fibres. At the
      equatorial region, three intrafusal fibres did not form a typical aggregation of
      nuclei such as bags and chains observed in common mammalian muscle spindles. Two
      intrafusal fibres of the three were innervated by sensory endings which branched
      and arranged irregularly. These sensory endings lay on the surface of intrafusal
      fibres in shallow grooves or deeply penetrated into the fibre. The third
      intrafusal fibre, lacking sensory innervation, showed a similar fine structure to
      extrafusal fibres. These findings suggest that the muscle spindle in the
      posterior cricoarytenoid muscle of the guinea pig is strikingly different in the
      structure of intrafusal fibres and in the arrangement of sensory endings from
      that in common mammalian skeletal muscles. The occurrence and role of these
      different structures were discussed.

PMID- 9279021
TI  - Analysis of single and multiple neuronal discharges as point processes: a
      computer program set.
AB  - The analysis of single or multiple neuron discharges as point processes has
      gained considerable importance for understanding the principles of information
      coding and processing in the central nervous system (CNS). Here, a set of
      programs written in BASIC language for microcomputers is described for the point
      process analysis of discharges of individual or multiple simultaneously recorded
      neurons as well as the mathematical basis of the methods implemented in these
      programs. The input data consist of one or more ASCII files with the spike or
      stimulus occurrence times generated by the spike sorting system used. Interspike
      interval histogram, autocorrelogram, autospectrum, cross-correlogram, joint
      impulse configuration scatter diagram, poststimulus time histogram and joint
      peristimulus time scatter diagram, together with other more conventional methods,
      are included in this package which provides graphical or alpha numeric results
      which can be printed or stored on disk for additional graphical or statistical
      analysis.

PMID- 9279022
TI  - [Histochemical characterization of glycoconjugates in the tongue of the toad Bufo
      marinus L. (Amphibian, anuran) with conventional techniques for light
      microscopy].
AB  - Histochemical stains with and without enzymatic digestions such as alpha-amylase,
      neuraminidase and hyaluronidase, made possible to localize and differentiate
      various types of glycoconjugates (GCs) in the tongue of the toad Bufo marinus. In
      the dorsal mucosae the covering epithelium of the filiform papillae, of the
      central folds and in the marginal cells of the fungiform papillae there were
      present large amounts of neutral GCs with little or no galactose and/or N
      acetylgalactosamine and scanty carboxylic acid GCs while the superficial strata
      of the taste organs showed a mixture of neutral an acid GCs with a predominance
      of sulfated and carboxylic acid GCs. The glandular secretory cells showed neutral
      GCs almost exclusively with a gradient of concentrations increasing from the base
      to the apex being galactose or N-acetyl-galactosamine one of the component
      sugars. The ventral epithelium showed two types of mucous cells, one with neutral
      GCs and the other with neutral and acidic GCs. The connective tissue contained
      many mast cells showing highly acid GCs both sulfated and carboxylic with some
      neutral GCs. The extracellular connective matrix showed scanty neutral and acid
      GCs. Glycogen was present in the cytoplasm of glandular epithelial cells and of
      the striated muscle fibers. Additionally, the obtained results suggest the
      presence of a type of GC with a carboxylic acid (sialic acid) resistant to
      neuraminidase of Clostridium perfringens used in this study.

PMID- 9279024
TI  - Effect of glucose-dependent insulinotropic polypeptide (GIP) on insulin response
      to glucose in acromegalics.
AB  - The pancreatic beta-cell response to stimulation with glucose and GIP, single and
      combined, was studied in acromegalics and in normal subjects. Acromegalics had
      higher IRI and GIP basal values with glucose levels and glucose disposal in the
      normal range. Further, acromegalics showed a greater IRI response to glucose, GIP
      and glucose combined with GIP. The results suggested that high growth hormone
      levels cause a greater activity of the entero-insular axis both in the basal
      state and after meal ingestion, as mimicked by GIP infusion. From these and
      previous observations, it can be assumed that growth hormone induces a
      facilitation of the IRI response to metabolite substrates and hormones.

PMID- 9279025
TI  - [Lectin histochemistry of the Bufo marinus L. toad tongue].
AB  - Lectin histochemistry at light microscope level was used in the tongue of the
      cane toad Bufo marinus to determine the distribution of sugar residues in
      glycoconjugates (GCs) previously localized and characterized by conventional
      histochemical techniques. Five horseradish-peroxidase (HRP) labeled-lectins,
      namely Con A, PNA, SBA, UEA-1 and WGS were used. Additionally, neuraminidase (N)
      treated sections before the staining procedures were used in order to dilucidate
      the presence of terminal sialic acid (SA). Sugar residues in GCs of the taste
      organ (TO) associated mucous cells stained more intensely with WGA than with Con
      A and UEA-1. All the sensory cells reacted with Con A and WGA but one type of
      them were characteristically labeled by UEA-1. The glycocalix (gc) of the TOs
      resulted intensely stained with Con A and with WGA and UEA-1 before and after N
      treatment. The GCs in the mucous-supporting cells of dorsal mucosae filiform
      papillae and folds reacted intensely with WGA and weakly with Con A. The ciliated
      cells (cic) were intense and characteristically stained with UEA-1 and WGA and
      moderately with Con A. The gc reacted more intensely with WGA than with Con A.
      Dorsal mucosae glands secretory cells mucins were characteristically stained with
      PNA, SBA and WGA besides Con A, while glandular ciliated cells showed the same
      staining pattern as in the filiform papillae. In the ventral mucosa all
      epithelium cells resulted stained with WGA and Con A, while differentiated goblet
      cells only reacted as well with UEA-1 and PNA before and after neuraminidase
      treatment. Unexpectedly, ciliated ventral mucosae cells did not react with UEA-1
      but only with WGA and Con A. The results have shown that lectin histochemistry is
      an interesting tool to characterize similarities and differences in the lingual
      GCs sugar residues composition and distribution, particularly those located in
      epithelial cells.

PMID- 9279026
TI  - [Natural products from the tropical rain forest of Venezuela as inhibitors of HIV
      1 replication].
AB  - More than 100 plant extracts from the Amazonian rain forest of Venezuela were
      evaluated for their cytotoxicity and inhibitory activity against the human
      immunodeficiency virus type-1 (HIV-1). Aqueous extracts from Fomitella supina (S
      # 0389-4), Phellinus rhabarbarinus (S # 0389-7), Trichaptum perrottetti (S # 0389
      8) and Trametes cubensis (S # 0389-13), Polyporaceae exhibited strong anti-HIV-1
      activity, without toxicity for Molt-4 lymphocytic cells. Our results
      demonstrated, that the compound(s) acted by mechanism of direct virion
      inactivation and by inhibition of syncytium formation in an in vitro culture
      system. These results support the suggestion that the test extracts specifically
      act at the level of CD4-gp120 binding. The active components of these extracts is
      at present unknown, but anti-AIDS agents, such as those found in this study,
      individually or in combination, may be of therapeutic relevance.

PMID- 9279027
TI  - [Nutritional value and antinutritional factor content of precooked flours
      prepared from Canavalia ensiformis].
AB  - Precooked flours obtained five Canavalia ensiformis varieties were prepared by
      dehydration in double drums. On a dry matter basis, significant differences (P <
      0.05) among varieties were detected for crude protein content (25 to 30%), starch
      (36 to 40%) and dietary fiber (13 to 15%). Hemagglutinins were eliminated as
      result of the high temperature (146 degrees C/4 min) employed during the drying
      process. Similar results were not obtained for trypsin inhibitors and canavanine
      considering that small amounts of these compounds remained in the precooked
      flours prepared from canavalia seeds. A 10% decrease in available lysine was
      observed. Biological assays yielded Protein Efficiency Ratio (PER) values of 0, 8
      1 and Neat Proteic Relation (NPR) values of 2-3-2.6. True digestibility of
      protein values were improved from 87 to 90%. All cultivars had similar starch
      digestive utilization coefficient (96%) and starch fraction (4%) resistant to
      enzymatic hydrolysis in the rat digestive tract.

PMID- 9279029
TI  - [Production of an acid extract of rice straw].
AB  - The chemical composition of rice straw was determined by means of standard
      analytical procedures. The material showed an adequate content of potentially
      assimilable carbohydrates for the growth of microorganisms. The optimum result of
      the rice straw treatment corresponds to a particle size of 60 mesh mixed with 5%
      H2SO4 in a weight: volume relation of 1:10 and submitted to a temperature of 121
      degrees C. Under these conditions a rice straw's acid extract was obtained,
      containing 20 g/lt of total sugars and 15 g/lt of reducing sugars. This content
      of sugars is enough to support the growth of microorganisms in aerobic
      conditions.

PMID- 9279028
TI  - [Optimization of the pertussis vaccine production process].
AB  - The production of Pertussis Vaccine was reevaluated at the Instituto Nacional de
      Higiene "Rafael Rangel" in order to optimise it in terms of vaccine yield,
      potency, specific toxicity and efficiency (cost per doses). Four different
      processes, using two culture media (Cohen-Wheeler and Fermentacion Glutamato
      Prolina-1) and two types of bioreactors (25 L Fermentador Caracas and a 450 L
      industrial fermentor) were compared. Runs were started from freeze-dried strains
      (134 or 509) and continued until the obtention of the maximal yield. It was found
      that the combination Fermentacion Glutamato Prolina-1/industrial fermentor,
      shortened the process to 40 hours while consistently yielding a vaccine of higher
      potency (7.91 +/- 2.56 IU/human dose) and lower specific toxicity in a mice
      bioassay. In addition, the physical aspect of the preparation was rather
      homogeneous and free of dark aggregates. Most importantly, the biomass yield more
      than doubled those of the Fermentador Caracas using the two different media and
      that in the industrial fermentor with the Cohen-Wheeler medium. Therefore, the
      cost per doses was substantially decreased.

PMID- 9279030
TI  - [Comparison of the environmental radioactivity in soils and sediments from Los
      Roques Archipelago with values of the Margarita Island and the Venezuelan
      continental coast].

PMID- 9279031
TI  - Successful aging.
AB  - Substantial increases in the relative and absolute number of older persons in our
      society pose a challenge for biology, social and behavioral science, and
      medicine. Successful aging is multidimensional, encompassing the avoidance of
      disease and disability, the maintenance of high physical and cognitive function,
      and sustained engagement in social and productive activities. Research has
      identified factors predictive of success in these critical domains. The stage is
      set for intervention studies to enhance the proportion of our population aging
      successfully.

PMID- 9279032
TI  - Values in health care professional socialization: implications for geriatric
      education in interdisciplinary teamwork.
AB  - The development of an identity and pattern of practice in the health care
      professions is based on a process of socialization into the roles and norms of a
      particular discipline and has important implications for clinical practice with
      elderly persons. Presented is a model for understanding the socialization process
      of physicians, nurses, and social workers as the development of professional
      meaning ("voice") based on the acquisition of value orientations or themes
      intrinsic to their education and training. The implications of these patterns for
      the abilities of different professions to work together collaboratively in the
      care of older persons are highlighted as a framework for developing new
      interdisciplinary curricular models in gerontological and geriatric education.

PMID- 9279033
TI  - Gender, the state, and constructing the old as dependent: lessons from the
      economic transition in Poland.
AB  - To critically examine the notion of the old as a "burden" to society, we use a
      political economic and gender-sensitive approach to explore the impact of the
      economic transition in Poland on retirement. Poland is an especially useful case
      for analyzing ways that divergent political economies shape the aging experiences
      of men and women, as differences between the two systems cannot be attributed to
      cultural variations. Overall, we find that old-age dependence in Poland is not
      inevitable; it is not created in a uniform manner for men and women; and it is
      not passively accepted by the old. Further, by examining economic activities in
      general, we show that retired men and women have been and are critical to the
      viability of both economic systems, albeit in different ways.

PMID- 9279034
TI  - The escape from poverty among rural and urban elders.
AB  - Do poor elders really leave poverty? We explore the prevalence and nature of
      exits from poverty among poor elders, with special attention to rural-urban
      differences in this regard. Analyzing twenty years of data from the Panel Study
      of Income Dynamics, we find that 40% of poor elders leave poverty after one year.
      However, descriptive data suggest many of these exits resulted from small
      increases in income that merely nudged elders over the poverty line.
      Nonmetropolitan elders are less likely to exit poverty than their metropolitan
      counterparts, and this disadvantage widened when statistical controls were
      applied in multivariate models.

PMID- 9279036
TI  - The financial burden of prescription drug use among elderly persons.
AB  - Expenditures for prescription drugs are not covered by Medicare and are thus a
      potential source of large out-of-pocket expenditures for elderly persons. This
      study, using a new data source, the 1990 Elderly Health Supplement to the Panel
      Study of Income Dynamics (PSID), demonstrates that, among elderly persons,
      insurance coverage for drugs reduces the fraction of household income spent on
      prescription drugs by 50 percent. Groups most likely to benefit from insurance
      coverage are elderly women and those with common chronic conditions, low incomes,
      and rural residences.

PMID- 9279035
TI  - Risk factors for reported elder abuse and neglect: a nine-year observational
      cohort study.
AB  - To determine longitudinal risk factors for elder abuse and neglect, an
      established cohort of community-dwelling older adults (n = 2,812) was linked with
      elderly protective service records over a 9-year follow-up period. Protective
      services saw 184 (6.5%) individuals in the cohort for any indication, and 47
      cohort members were seen for corroborated elder abuse or neglect for a sampling
      adjusted 9-year prevalence of 1.6% (95% CI 1.0%, 2.1%). In pooled logistic
      regression, age, race, poverty, functional disability, and cognitive impairment
      were identified as risk factors for reported elder mistreatment. Additionally,
      the onset of new cognitive impairment was also associated with elder abuse and
      neglect. Because the mechanism of elder mistreatment case-finding in this study
      was a social welfare system (protective services), the influence of race and
      poverty as risk factors is likely to be overestimated due to reporting bias.

PMID- 9279037
TI  - Factors predicting survival, changes in activity limitations, and disability in a
      geriatric post-stroke population.
AB  - This study is based on data for individuals with a history of stroke taken from
      the NIA-sponsored Longitudinal Study of Aging (LSOA), 1984-1990. It provides
      information on the factors predicting survival and changes in disability and
      activity limitations in this cohort with stroke or cerebrovascular accident over
      the period of two years, 1984 to 1986. The results indicate that individuals who
      were less than 80 years old had higher chances of survival and were likely to
      show reduced activity limitations and disabilities. It was also observed that the
      individuals who were in excellent health were more likely to survive despite a
      history of stroke. Individuals with severe activity limitations had a very low
      incidence of survival over the two-year period. Further, the results of this
      study support the contention that the increased use of health care resources in
      the form of visits to physicians, hospitals, and nursing homes results in
      improved survival and lower disability and activity limitations among the
      elderly.

PMID- 9279038
TI  - A cross-cultural validation of coping strategies and their associations with
      caregiving distress.
AB  - Coping strategies were compared among family caregivers of Alzheimer's disease
      patients in Shanghai, China (n = 110) and San Diego, California (n = 139). Four
      coping factors were reliably consistent in both samples, supporting their
      widespread relevance to life adversity; behavioral confronting, behavioral
      distancing/social support, cognitive confronting, and cognitive distancing.
      Shanghai and San Diego caregivers endorsed similar rates of coping, but Shanghai
      caregivers reported fewer symptoms of depression and anxiety. Although coping
      strategies were similar, cultural ideals promoting family interdependence,
      veneration of elderly family members, and acceptance of traditional family roles
      may have reduced the psychological impacts of caregiving in the Shanghai sample.

PMID- 9279039
TI  - New burdens or more of the same? Comparing grandparent, spouse, and adult-child
      caregivers.
AB  - This study compares the health of 42 grandparent, 44 spouse, and 130 adult-child
      caregivers with 1,669 noncaregivers in 1994 and 1974. In 1994, all three
      caregiver groups had poorer mental health than the noncaregivers; grandparent
      caregivers also had poorer physical health and greater activity limitations.
      Spouse and adult-child caregivers had not differed from the noncaregivers 20
      years prior, but grandparent caregivers had experienced poorer health than the
      noncaregivers and more stressful life events than the other caregivers.
      Caregiving appears to add new burdens to otherwise normal lives for spouse and
      adult-child caregivers, while being yet another aspect of a difficult life course
      for grandparent caregivers.

PMID- 9279040
TI  - Findings from a statewide program of respite care: a comparison of service users,
      stoppers, and nonusers.
AB  - This study compared respite users with stoppers and nonusers in the Health
      Resources and Services Administration-funded Alzheimer's disease demonstration
      grant in the State of Maryland. Of those accepted into the program, only 54%
      participated for at least 6 months. The primary reasons for stopping were the
      death or institutionalization of the relative, while those not using respite
      services felt they didn't really need them. Determinants of program use included
      the poorer cognitive status of the relative and less anxiety and greater burden
      among the caregivers. After 6 months, users reported fewer hours of informal
      assistance, less burden, and that the relative had fewer behavioral problems
      although cognitive status and activities of daily living (ADLs) had deteriorated.

PMID- 9279041
TI  - Criteria for placing older adults in public conservatorship: age as proxy for
      need.
AB  - This study was conducted on a sample of 589 adult public conservatees in Los
      Angeles County, California, to determine whether the process used to assign them
      into conservatorship is age-blind, as California law suggests. Findings indicate
      that age is not associated with the amount of time spent evaluating adults for
      conservatorship but that increasing age, rather than need, is associated with
      assignment into Probate conservatorship. The association of age with Probate
      conservatorship appears to result from the vagueness of the criteria for Probate
      conservatorship-unable to manage-resulting in the use of age as a proxy for need
      in the case of decisionally impaired older adults.

PMID- 9279042
TI  - Policy without technology: a barrier to improving nursing home care.
AB  - Standards of care are written for nursing homes without a realistic assessment of
      whether there is an intervention protocol or resources to meet these standards.
      This situation produces unfair pressures on nursing home providers, who react
      with paper compliance strategies, and creates a barrier to implementing new
      interventions that do meet care standards once they are developed. This article
      explores this barrier and illustrates examples of interventions that have been
      attempted in nursing homes using a continuous quality improvement model. The
      development of quality indicators based on assessment data available in all
      nursing homes is a step toward making the survey process more focused on outcomes
      rather than on paper compliance. Much more research is needed to design effective
      clinical interventions and to provide nursing homes with the technologies
      necessary to target them. Internal nursing home quality assurance programs based
      on principles of continuous quality improvement, with reinforcement from the
      external survey process, are suggested as a strategy to maintain clinically
      effective interventions. Applied research centers based in long-term care
      facilities should be supported in order to accomplish such research designed to
      improve the care and quality of life our increasing frail nursing home
      population.

PMID- 9279043
TI  - The influence of community context on the preferences of older adults for
      entering a nursing home.
AB  - Previous research has established that rural elders are more likely to enter a
      nursing home than elders living in suburban and urban areas. This research
      examined preferences for long-term care alternatives using a telephone survey of
      community-dwelling elders (age 65+). In contrast to admission patterns, urban
      elders were more likely to prefer nursing home care if unable to live
      independently. This difference persisted in multinomial logit models that
      included other predictors of nursing home use. Thus, rural elders may be more
      likely to experience discrepancies between their preferred mode of long-term care
      and the actual outcomes that they may ultimately experience.

PMID- 9279045
TI  - The Wellness Group: a novel intervention for coping with disruptive behavior
      among [corrected] elderly nursing home residents.
AB  - Elderly nursing home residents face the challenge of coping with the loss of
      independence, reduced physical abilities, feelings of isolation, anxiety,
      depression, and helplessness. Maintaining one's integrity within the nursing home
      is a challenge easily lost. Issues of coping with disability, change in body
      image, the promotion of self-empowerment, and autonomy are critical to preserving
      the personhood of a nursing home resident. Current emphasis on the management of
      behavior has focused entirely on the control of disruption rather than the
      promotion of resident strengths and abilities. We developed a group therapy
      program designed to enhance self-awareness, self-esteem, and body awareness among
      the demented elderly. Techniques of meditation, relaxation, sensory awareness and
      guided imagery were introduced and reinforced. This group is easily reproducible
      and offers benefits to both residents and interdisciplinary staff.

PMID- 9279044
TI  - Selecting nursing home residents for satisfaction surveys.
AB  - Many cognitively impaired nursing home (NH) residents are excluded from
      interviews measuring quality of life or care based on the belief that these
      residents cannot accurately answer questions. These exclusions are based on
      subjective criteria and ignore individual differences among cognitively impaired
      NH residents. This study describes a screening rule based on four minimum data
      set (MDS) indicators that provides an objective method for identifying residents
      capable of accurate report. Sixty percent of a sample of 83 NH residents who
      could answer yes or no questions about their care could do so accurately. Eighty
      one percent of the sample was correctly classified by the MDS indicators.

PMID- 9279046
TI  - Optometric co-management: a paradigm for pediatric eye care delivery.

PMID- 9279047
TI  - Corneal responses to lens transmissibility.
AB  - BACKGROUND: Lens transmissibility (Dk/L) and corneal relief from hypoxia are not
      linearly related. We describe graphically and by equations the relationship
      between corneal relief (scaled in oxygen shortfall units) and Dk/L across the
      transmissibility range of 1.2 to 189 x 10(-9) (cm/sec)(ml O2/ml mmHg). METHODS:
      Corneal responses to 28 Dk/L levels across the transmissibility range were
      expressed in oxygen shortfall units (osus), a relative scale of 100 steps bounded
      by each cornea's normal oxygen uptake rate with no contact lens in place (set =
      to 0 osus), and its maximum uptake rate for the open eye due to static PMMA lens
      wear (set = to 100), thus allowing the degree of hypoxic stress exhibited by all
      corneas to be compared on the same relative scale. RESULTS: Responses of 11 human
      corneas to each of those 28 Dk/L steps were recorded across that entire
      transmissibility range, and their collective relationship described graphically.
      CONCLUSION: The graphic composite of all corneal responses to transmissibility
      steps across the Dk/L range of 1.2 to 189 X 10(-9) (cm/sec)(ml O2/ml mmHg) was
      found to be monotonic and continuous. While no single equation was found that
      optimally described (predicted) corneal responses across that entire spectrum,
      equations of the quadratic form fit limited domains of Dk/L (r2 values exceeding
      90%) adequately for most laboratory and clinical applications.

PMID- 9279048
TI  - Optometric management of patients with Alzheimer's disease.
AB  - BACKGROUND: The earliest symptoms of Alzheimer's disease (AD) may be visual. AD
      is an age-related, progressive dementia. At least 7% of Americans over 65 years
      of age are afflicted, and it ranks as the fourth leading cause of death in the
      United States. A review of the literature was performed to delineate the visual
      manifestations of Alzheimer's disease. RESULTS: Abnormal visual perception and
      visuospatial processing are common among patients with AD Visual acuity,
      pupillary light reflexes, and the ocular fundus do not appear to be specifically
      affected by AD. Whether AD impairs color vision is controversial. Stereopsis may
      also be affected. True visual-field defects are rarely found. Although not
      universally reported, some studies of contrast sensitivity functions show
      abnormal sensitivity possibly at low spatial frequencies. The electroretinogram
      is normal, while the visual evoked response is frequently abnormal. CONCLUSIONS:
      As primary eye care providers, optometrists must properly identify and refer
      individuals with suspected Alzheimer's disease to the appropriate specialist, as
      well as manage their visual welfare.

PMID- 9279049
TI  - Prescribing for the moderate-to-advanced ametropic presbyopic VDT user. A
      comparison of the Technica Progressive and Datalite CRT trifocal.
AB  - BACKGROUND: Use of video display terminals (VDTs) is expected to dramatically
      increase. This clinical study was performed to examine the moderate-to-advanced
      ametropic presbyopic VDT user to determine the most prevalent visual or physical
      symptoms incurred while working at a VDT, and to develop a comparative benefit
      analysis of two currently available occupational lens designs. METHODS: Twenty
      four symptomatic VDT users who were currently wearing a non-occupational lens
      design were selected from a pool of 100 applicants. The non-occupational lens
      distribution included 17 bifocals, 3 trifocals and 4 progressives lenses. The
      subjects compared two occupational lens designs. RESULTS: Statistical analyses
      indicated that the frequency and severity of seven of 10 symptoms reported were
      significantly reduced by wearing the occupational lenses, including the three
      most frequently reported pre-existing symptoms of neck/shoulder aches, eyestrain,
      and blurred intermediate vision. CONCLUSION: Study results suggest that
      symptomatic moderate-to-advanced ametropic presbyopic VDT users may benefit from
      an occupational progressive lens when work involves prolonged or exclusive
      viewing of a VDT screen. An occupational trifocal may benefit VDT users also
      required to perform other viewing tasks.

PMID- 9279050
TI  - Transient and sustained processing: effects of varying luminance and wavelength
      on reading comprehension.
AB  - BACKGROUND: Reading disability (RD) is a serious epidemiologic problem and may
      affect up to 15% to 20% of elementary school children. This study addresses
      whether the reading comprehension skills of children with RD improve as
      wavelength and contrast of light are altered. METHODS: Fifty-six children,
      identified as either normal or reading disabled, were required to read a series
      of standardized 300-word passages under four conditions: no filter (baseline);
      light gray filter, dark gray filter, and blue filter. Each reading selection was
      timed, reading comprehension was measured, and data were processed. RESULTS:
      Initial standardized reading comprehension test scores significantly
      differentiated average from poor readers. Using reading selection levels
      consonant with each subject's ability, no significant differences were measured
      in baseline comprehension scores between good and poor readers. Comprehension
      scores of poor compared to good readers were significantly better using blue
      filters (p < 0.01). CONCLUSIONS: Our study suggests an association between
      wavelength of light, luminance, and reading performance. Blue filters were found
      to improve reading comprehension in poor readers. The results support the concept
      of a transient system deficit involving wavelength of light and reading
      performance.

PMID- 9279051
TI  - Causes of blindness among Navajo Indians: an update.
AB  - BACKGROUND: The causes of blindness among Navajo Indians, an ethnically distinct
      community within the United States, were last studied in 1982. This article
      presents an updated report on the causes of blindness among the Navajo. METHODS:
      Staff optometrists at each of the hospitals and clinics on the Navajo Reservation
      collected information for each affected eye: date of onset, cause, blinding
      process, and best visual acuity. In terms of the total number of eyes affected,
      it was found that the most frequently encountered etiology was trauma, followed
      by congenital causes, diabetes mellitus, primary open-angle glaucoma, age-related
      macular degeneration, and trachoma. CONCLUSIONS: Considering raw numbers as well
      as preventability, it is suggested that trauma, diabetes mellitus, and primary
      open-angle glaucoma be targeted for a focused intervention of patient-as well as
      public-education aimed at reducing blindness from these causes.

PMID- 9279053
TI  - Herpes zoster ophthalmicus and the immunocompromised host: a case report and
      review.
AB  - BACKGROUND: Herpes zoster is the secondary form of varicella zoster virus
      disease, caused by the reactivation of the dormant virus in the sensory ganglia.
      It manifests as a unilateral cutaneous dermatitis with a prodromal fever and
      malaise. Herpes zoster ophthalmicus occurs when the ophthalmic division of the
      trigeminal nerve becomes afflicted. CASE REPORTS: This case represents a middle
      aged female with breast carcinoma. Cancer radiotherapy and chemotherapy created
      an immunosuppressed state, which allowed the development of herpes zoster
      ophthalmicus. Most patients who manifest zoster are immunocompetent. However,
      with the increased incidence of immunodeficient states (e.g., chemotherapy, organ
      transplantation and acquired immunodeficiency syndrome), clinicians are faced
      with a greater number of cases of zoster. In the immunodeficient population,
      especially, dissemination of the zoster and potentially damaging complications
      can occur. CONCLUSIONS: In the light of these facts, clinicians must be well
      versed in all aspects of herpes zoster disease, including the clinical and
      laboratory diagnosis, as well as the incidence and presentation of herpes zoster.
      Current treatments, such as the use of famciclovir, acyclovir, valcyclovir, and
      prednisone, must also be understood.

PMID- 9279052
TI  - Traumatic porencephalic cyst of the brain.
AB  - BACKGROUND: A porencephalic cyst is a cavity within the cerebral hemisphere,
      filled with cerebrospinal fluid, that communicates directly with the ventricular
      system. It is a rare condition probably caused by vascular occlusion resulting
      from an insult during fetal development or an injury occurring later in life.
      Porencephaly is often associated with various ophthalmic and neurologic signs,
      including visual-field defects, abnormal pupillary responses, optic nerve
      hypoplasia, decreased vision, nystagmus, strabismus, hemi-inattention, seizures,
      and mental deficiencies. CASE REPORTS: Two cases are presented of patients in
      whom porencephalic cysts developed as a result of traumatic head injuries. Both
      had demonstrable visual-field defects, with diagnosis of porencephaly verified by
      computed tomography scans of the head. CONCLUSIONS: Visual-field defects
      resulting from porencephalic cysts can mimic those observed with strokes or brain
      tumors. A thorough case history and complete neurologic workup can assist with
      differential diagnosis. The clinical features of porencephaly, different theories
      of brain recovery after trauma, and treatment options are discussed.

PMID- 9279054
TI  - Strategies of the Pan American Health Organization/World Health Organization for
      the control of iron deficiency in Latin America.
AB  - Iron deficiency anemia is one of the major micronutrient deficiencies in the
      world. Its etiology is well understood, and inexpensive solutions to the problem
      have been identified. Nevertheless, the problem persists. This paper estimates
      the magnitude of iron deficiency anemia and presents strategies suggested by the
      Pan American Health Organization of the World Health Organization (PAHO/WHO) for
      adoption by individual countries.

PMID- 9279055
TI  - Preventing iron deficiency in infants and preschool children in Argentina.
AB  - This paper summarizes the results of most major studies of iron deficiency and
      anemia in infants and children in Argentina. Possible reasons for high
      prevalences of iron deficiency and anemia in certain population groups are given,
      and plans for future interventions, based on these data, are discussed.

PMID- 9279056
TI  - Iron supplementation for the control of iron deficiency in populations at risk.
AB  - Iron supplementation, mostly with a therapeutic orientation, has been a key
      strategy for the short-term control of iron deficiency and ferropenic anemia. It
      has been used almost exclusively in antenatal clinics, but in spite of its
      confirmed efficacy in supervised trials, it has proven ineffective in practice in
      most developing countries. Poor effectiveness has been attributed to various
      factors including insufficient dose and time of supplementation and poor
      adherence. These problems have led to the administration of high iron doses,
      which have proven equally ineffective in practice. This paper introduces four
      concepts: (1) that iron supplementation targeted to pregnant women should cover
      the full reproductive cycle, from prepregnancy to at least the end of lactation
      instead of only the pregnant women; (2) that entering pregnancy with iron
      deficiency contributes to the failure of antenatal iron supplementation and that
      prepregnancy iron reserves increase the effectiveness of antenatal
      supplementation; (3) that medium- to long-term weekly ingestion of proper iron
      folate supplements, with a preventive aim and directed to all risk groups, should
      be community based rather than health service based but supervised by the latter
      (in this sense, preventive supplementation is equal to targeted iron
      fortification); and (4) that preventive supplementation, based on weekly dosing,
      has proven efficacious. Problem-oriented research to evaluate the sustainability
      and medium- to long-term efficacy of these concepts is called for. The bases for
      the concepts and suggestions are summarized in this paper.

PMID- 9279057
TI  - Preventing iron deficiency through food fortification.
AB  - One way to prevent iron deficiency anemia in developing countries is through the
      fortification of food products with iron. In addition to avoiding undesirable
      color and flavor changes, the main challenge is to protect the fortification iron
      from potential inhibitors of iron absorption present in commonly fortified foods.

PMID- 9279058
TI  - Hookworm control as a strategy to prevent iron deficiency.
AB  - The hookworms Necator americanus and Ancylostoma duodenale infect approximately 1
      billion people worldwide. The prevalence of hookworm infection increases with age
      in children, typically reaching a plateau in late adolescence, whereas the
      intensity of infection may continue to increase throughout adulthood. Hookworms
      cause intestinal blood loss in amounts proportional to the number of adult worms
      in the gut. The relationship between hookworm infection intensity and hemoglobin
      concentration is evident in epidemiologic studies, but may be apparent only above
      a threshold worm burden that is related to the iron stores of the population.
      Current hookworm control efforts are focused on reducing infection load and
      transmission potential through periodic anthelminthic chemotherapy. Several
      controlled trials have demonstrated a positive impact of anthelminthic treatment
      on hemoglobin levels, with best results obtained in settings where iron intakes
      were also increased. Evidence suggests that anthelminthic programs will have
      modest impacts on iron deficiency anemia in the short term, with greater impacts
      on more severe anemia. Hookworms are an important cause of anemia in women, who
      are often overlooked by current helminth control programs. Current WHO
      recommendations for use of anthelminthics in schoolchildren and women are
      reviewed. There is a need to clarify whether hookworms are an important etiology
      of iron deficiency anemia in preschool children.

PMID- 9279059
TI  - Strategies for the prevention of iron deficiency through foods in the household.
AB  - Iron deficiency can be caused not only by diets deficient in iron but by poor
      absorption of available dietary iron. Extrinsically tagging foods with radioiron
      allows the exact measurement of iron absorbed from heme and nonheme iron foods.
      It has furthered the study of the effect of enhancers and inhibitors of iron
      absorption. As a result, we have a greater understanding of why iron deficiency
      and iron deficiency anemia are prevalent in populations of low socioeconomic
      status and of which food vehicles and iron compounds are most suitable for iron
      fortification.

PMID- 9279060
TI  - A new procedure to fortify fluid milk and dairy products with high-bioavailable
      ferrous sulfate.
AB  - The behavior of SFE-171 used for food fortification was studied. The biological
      and nutritional properties of this new iron source are discussed in this work.

PMID- 9279061
TI  - Definition and prevalence of anemia in Bolivian women of childbearing age living
      at high altitudes: the effect of iron-folate supplementation.
AB  - This paper discusses the effect that high altitudes have on iron metabolism and
      summarizes the results of an iron-folate supplementation trial. The two main
      objectives of the trial were to determine hemoglobin cut-off values for the
      diagnosis of anemia in Bolivian women of childbearing age living at high
      altitudes, and to estimate the prevalence of anemia in this population. The study
      showed that nutritional anemia is an important public health problem in such
      populations and that many methods of assessing it lead to an underestimation of
      prevalence. The cut-off values defined through this study, one of the few iron
      supplementation trials conducted at high altitudes, confirm the need to establish
      revised hemoglobin values for the diagnosis of anemia in populations living at
      high altitudes.

PMID- 9279062
TI  - Retinoyl beta-glucuronide: a biologically active form of vitamin A.
AB  - Retinoyl beta-glucuronide is a naturally occurring, biologically active
      metabolite of vitamin A. Although retinoyl beta-glucuronide is regarded as a
      detoxification product of retinoic acid, it plays several roles in the functions
      of vitamin A. It can serve as a source of retinoic acid, and it may be a vehicle
      for transport of retinoic acid to target tissues. Topically applied retinoyl beta
      glucuronide is comparable in efficacy to retinoic acid in the treatment of acne
      in humans, without the same side effects. Retinoyl beta-glucuronide may or may
      not be teratogenic, depending on the mode of administration and the species in
      which it is used. It may be a valuable therapeutic compound for the treatment of
      skin disorders and certain types of cancers.

PMID- 9279063
TI  - Women, food, and mood.
AB  - Associations between food intake and mood greatly interest both lay and
      scientific audiences, although scientific support for many observed associations
      is sparse. Of particular interest are issues surrounding food intake, food
      cravings, and mood in women throughout the menstrual cycle. Further research is
      necessary to support or disprove current hypotheses about the relationship
      between food intake and mood. Meanwhile, health professionals should be prepared
      to inform the public about the complexity of factors that influence the
      relationship between food intake and mood.

PMID- 9279064
TI  - Dietary selenium repletion may reduce cancer incidence in people at high risk who
      live in areas with low soil selenium.
AB  - Studies examining the relationship between dietary selenium intake and risk of
      various cancers have shown that low selenium intake is associated with higher
      cancer rates. A recent well-controlled intervention trial studied whether
      selenium supplementation can prevent cancer in subjects who have a history of
      skin cancer and live in areas of the United States with low soil selenium levels.
      Selenium supplementation did not reduce skin cancer rates, but the incidence of
      total, lung, colorectal, and prostate cancers was significantly reduced by the
      intervention. Although these data need confirmation, they suggest that adequate
      selenium intake is essential for cancer prevention.

PMID- 9279065
TI  - Enteral nutrition in acute pancreatitis.
AB  - A recent prospective and randomized study comparing enteral nutrition with total
      parenteral nutrition has shown that enteral nutrition may be a cost-effective
      alternative to total parenteral nutrition in patients with acute pancreatitis.

PMID- 9279066
TI  - Skeletal functions of vitamin K-dependent proteins: not just for clotting
      anymore.
AB  - Osteocalcin and matrix Gla protein (MGP) are two vitamin K-dependent proteins
      present in bone and cartilage. Transgenic mice models were recently developed to
      isolate the function of each of these proteins. While osteocalcin-deficient mice
      have increased bone formation, MGP-deficient mice have abnormal calcification
      leading to osteopenia, fractures, and premature death owing to arterial
      calcification.

PMID- 9279067
TI  - High bone mass as a marker for breast cancer risk.
AB  - Postmenopausal women in the highest quartile for metacarpal bone mass were found
      to have an increased risk of developing breast cancer, after adjusting for age
      and other variables known to influence breast cancer risk. Although the
      mechanisms responsible for this relationship have not been identified,
      postmenopausal bone mass may serve as an indicator of cumulative estrogen
      exposure.

PMID- 9279068
TI  - [Discoveries of oncogenes and tumor suppressor genes].

PMID- 9279069
TI  - [A flow of oncogene research: from oncogene to signal transduction].

PMID- 9279070
TI  - [Tumor angiogenesis and Flt tyrosine kinase].

PMID- 9279071
TI  - [The function of receptor protein tyrosine kinases: cell growth and more].

PMID- 9279072
TI  - [Signal transduction through SH2, SH3 and PH domains].

PMID- 9279073
TI  - [An adapter molecule, Cas, is involved in cell attachments].

PMID- 9279074
TI  - [Functions and modes of action of Ras and Rho small GTP-binding proteins].

PMID- 9279075
TI  - [Signal transduction pathways by MAP kinase cascades].

PMID- 9279076
TI  - [TGF-beta signaling].

PMID- 9279077
TI  - [Cytokine signaling].

PMID- 9279078
TI  - [Interaction between a transforming protein tax and cellular factors].

PMID- 9279079
TI  - [Cell to substratum adhesion signaling].

PMID- 9279080
TI  - [Tumor suppressor genes and cell cycle control].

PMID- 9279081
TI  - [G1-cyclin/Cdk and cancer].

PMID- 9279082
TI  - [CDK inhibitors].

PMID- 9279083
TI  - [p53 mutations and their role in tumorigenesis].

PMID- 9279084
TI  - [Induction of the p53 response].

PMID- 9279085
TI  - [Regulation of cell growth by the transcription factor p53, a tumor suppressor
      gene product].

PMID- 9279086
TI  - [Cell-cycle regulation via phosphorylation of RB protein by cyclin-dependent
      kinase].

PMID- 9279088
TI  - [The Wilms' tumor suppressor gene WT1].

PMID- 9279087
TI  - [Cell growth control by the E2F transcription factor].

PMID- 9279089
TI  - [Interaction of viral transforming gene products and tumor suppressor gene
      products].

PMID- 9279090
TI  - [Cancer and apoptosis].

PMID- 9279091
TI  - [Caspase family proteases and apoptosis].

PMID- 9279092
TI  - [Fatty acids-induced apoptosis].

PMID- 9279093
TI  - [Regulation of cell death by Bcl-2 family].

PMID- 9279094
TI  - [Regulation of apoptosis during lymphocyte development].

PMID- 9279095
TI  - [p53-mediated apoptosis].

PMID- 9279097
TI  - [Cadherin superfamily: structural and functional properties of cadherins].

PMID- 9279096
TI  - [Cell adhesion and tumor metastasis].

PMID- 9279098
TI  - [Molecular organization and functions of tight junction].

PMID- 9279099
TI  - [Molecular mechanisms of integrin-ligand interaction].

PMID- 9279100
TI  - [Cell transformation by Src kinase: role of cell adhesion system as a signal
      transducer].

PMID- 9279101
TI  - [Matrix metalloproteinases and cancer cell invasion and metastasis].

PMID- 9279102
TI  - [Invasion and metastasis of cancer and nuclear oncogenes].

PMID- 9279103
TI  - [Genetic alterations and genetic diagnosis of human cancer].

PMID- 9279104
TI  - [Hereditary tumor].

PMID- 9279105
TI  - [Colorectal cancers].

PMID- 9279106
TI  - [Lung cancer].

PMID- 9279107
TI  - [Stomach cancer].

PMID- 9279108
TI  - [Hepatocellular carcinoma].

PMID- 9279109
TI  - [Breast cancers].

PMID- 9279111
TI  - [Gene therapy of cancer: an overview].

PMID- 9279110
TI  - [Gynecologic malignancies].

PMID- 9279112
TI  - [Current status of cancer gene therapy research].

PMID- 9279113
TI  - [The strategy of cancer gene therapy].

PMID- 9279114
TI  - [Gene therapy vector: retroviral vector].

PMID- 9279115
TI  - [Gene therapy vector: adenovirus vector].

PMID- 9279116
TI  - [Liposome-mediated gene delivery].

PMID- 9279117
TI  - [Polysemous codon found in Candida species].

PMID- 9279118
TI  - [Representational difference analysis: its principle and versatile applications].

PMID- 9279119
TI  - [Triplet repeat disorders: from the clinical view].

PMID- 9279120
TI  - [Metabolism of Alzheimer's amyloid precursor protein].

PMID- 9279121
TI  - [Expression patterns and functions of plant homeobox genes during embryogenesis].

PMID- 9279122
TI  - [Analyses of neuronal function, gene expression and chromosome structure using
      micro-sensor probes].

PMID- 9279123
TI  - Secondary structure dependent on metal ions of copper,zinc superoxide dismutase
      investigated by Fourier transform IR spectroscopy.
AB  - Copper, zinc superoxide dismutase (Cu2Zn2-SOD) from bovine erythrocyte and its
      metal ion free derivatives, E2Zn2-SOD, Cu2E2-SOD, and E2E2-SOD (E: empty) were
      prepared and their secondary structures were investigated by Fourier transform ir
      spectroscopy. In 20 mM deuterated phosphate buffer (pD 7.5) solution at room
      temperature, the native Cu2Zn2-SOD contains about 34% beta-strand, 17% beta-turn,
      and 49% unordered structures, which is similar to the content determined by x-ray
      crystal structural analysis. The metal ion free derivatives decrease the
      component of beta-strand and increase the unordered structure component in trend.
      Especially in the cases of zinc-free derivatives, Cu2E2-SOD and E2E2-SOD, about
      24% beta-strand, 20% beta-turn, and 57% unordered structures are obtained. The
      result indicates that the zinc ion plays an important role in determining the
      secondary structure of copper,zinc superoxide dismutase.

PMID- 9279124
TI  - Structure determination and synthesis of lysine isopeptides influencing on cell
      proliferation.
AB  - The clavicepamines are lysine-rich basic proteins isolated from saprophytic
      culture of ergot (Claviceps purpurea), having human pharmacological importance.
      Based on structure determinations, it was demonstrated that the epsilon-lysine
      (poly)peptides are the fundamental structural units of clavicepamines. To study
      the relationship between chemical structure and biological effect, solution and
      solid-phase synthesis of lysine isopeptides were performed. Poly-epsilon-lysines
      were synthesized with polycondensation via application of p-nitrophenylester
      temporarily protecting groups together with simultaneous activation. The
      biological investigations of poly-epsilon-lysines showed a cell-proliferation
      retarding effect, so they inhibit growth of some animal tumors, practically
      without toxic side effects.

PMID- 9279126
TI  - Tyrosine mutant helps define overlapping CD bands from fd gene 5 protein.nucleic
      acid complexes.
AB  - We used a mutant gene 5 protein (g5p) to assign and interpret overlapping CD
      bands of protein nucleic acid complexes. The analysis of overlapping protein and
      nucleic acid CD bands is a common challenge for CD spectroscopists, since both
      components of the complex may change upon binding. We have now been able to more
      confidently resolve the bands of nucleic acids complexed with the fd gene 5
      protein by exploiting a mutant gene 5 protein that has an insignificant change in
      tyrosine optical activity at 229 nm upon binding to nucleic acids. We have
      studied the interactions of the mutant Y34F g5p (Tyr-34 substituted with
      phenylalanine) with poly[r(A)], poly[d(A)], and fd single-stranded DNA (ssDNA).
      Our results showed the following: (1) The 205-300 nm spectrum of poly[r(A)]
      saturated with the Y34F mutant (P/N = 0.25) was essentially the sum of the
      spectra of poly[r(A)] at a high temperature plus the spectrum of the free
      protein, except for a minor negative band at 257 nm. (2) The spectra of
      poly[d(A)] and fd ssDNA saturated with the mutant protein at a P/N = 0.25, minus
      the spectra of the free nucleic acids at a high temperature, also essentially
      equaled the spectrum of the free protein in the 205-245 nm region. (3) While the
      overall secondary structure of the Y34F protein did not change upon binding to
      any of these nucleic acids, there could be changes in the environment of
      individual aromatic residues. (4) Nucleic acids complexed with the g5p are
      unstacked (as if heated) and (in the cases of the DNAs) perturbed as if part of a
      dehydrated double-stranded DNA. (5) Difference spectra revealed regions of the
      spectrum specific for the particular nucleic acid, the protein, and whether g5p
      was bound to DNA or RNA.

PMID- 9279127
TI  - Enzymes that regulate ethylene levels--1-aminocyclopropane-1-carboxylic acid
      (ACC) deaminase, ACC synthase and ACC oxidase.
AB  - The plant enzymes, 1-aminocyclopropane-1-carboxylic acid (ACC) synthase and ACC
      oxidase, catalyze essential steps in the biosynthesis of the phytohormone
      ethylene; the microbial enzyme ACC deaminase catalyses the hydrolytic cleavage of
      ACC, the immediate precursor of ethylene, and is therefore an inhibitor of
      ethylene biosynthesis. In this manuscript, the biochemical properties and
      mechanisms of these three enzymes and the genes that encode them are examined and
      compared. Despite the fact that ACC oxidase and ACC deaminase both act on the
      same substrate, i.e., ACC, these two enzymes and the mechanisms that they employ
      are quite different. Conversely, although ACC synthase catalyses the synthesis of
      ACC and ACC deaminase catalyses its hydrolysis, these enzymes share a number of
      important physical and biochemical properties.

PMID- 9279125
TI  - Substrate binding and catalytic mechanism in phospholipase C from Bacillus
      cereus: a molecular mechanics and molecular dynamics study.
AB  - For the first time a consistent catalytic mechanism of phospholipase C from
      Bacillus cereus is reported based on molecular mechanics calculations. We have
      identified the position of the nucleophilic water molecule, which is directly
      involved in the hydrolysis of the natural substrate phosphatidylcholine, in
      phospholipase C. This catalytically essential water molecule, after being
      activated by an acidic residue (Asp55), performs the nucleophilic attack on the
      phosphorus atom in the substrate, leading to a trigonal bipyramidal
      pentacoordinated intermediate (and structurally similar transition state). The
      subsequent collapse of the intermediate, regeneration of the enzyme, and release
      of the products has to involve a not yet identified second water molecule. The
      catalytic mechanism reported here is based on a series of molecular mechanics
      calculations. First, the x-ray structure of phospholipase C from B cereus
      including a docked substrate molecule was subjected to a stepwise molecular
      mechanics energy minimization. Second, the location of the nucleophilic water
      molecule in the active site of the fully relaxed enzyme-substrate complex was
      determined by evaluation of nonbonded interaction energies between the complex
      and a water molecule. The nucleophilic water molecule is positioned at a distance
      (3.8 A) from the phosphorus atom in the substrate, which is in good agreement
      with experimentally observed distances. Finally, the stability of the complex
      between phospholipase C, the substrate, and the nucleophilic water molecule was
      verified during a 100 ps molecular dynamics simulation. During the simulation the
      substrate undergoes a conformational change, but retains its localization in the
      active site. The contacts between the enzyme, the substrate, and the nucleophilic
      water molecule display some fluctuations, but remain within reasonable limits,
      thereby confirming the stability of the enzyme-substrate-water complex. The
      protocol developed for energy minimization of phospholipase C containing three
      zinc ions located closely together at the bottom of the active site cleft is
      reported in detail. In order to handle the strong electrostatic interactions in
      the active site realistically during energy minimization, delocalization of the
      charges from the three zinc ions was considered. Therefore, quantum mechanics
      calculations on the zinc ions and the zinc-coordinating residues were carried out
      prior to the molecular mechanics calculations, and two different sets of partial
      atomic charges (MNDO-Mulliken and AMI-ESP) were applied. After careful assignment
      of partial atomic charges, a complete energy minimization of the protein was
      carried out by a stepwise procedure without explicit solvent molecules. Energy
      minimization with either set of charges yielded structures, which were very
      similar both to the x-ray structure and to each other, although using AMI-ESP
      partial atomic charges and a dielectric constant of 4, yielded the best protein
      structure.

PMID- 9279128
TI  - Recent advances in diagnosis of filarial infections.
AB  - Improved diagnostic methods for human filariasis are needed to facilitate
      surveillance activities, to monitor control efforts and to evaluate new drugs and
      vaccines. Currently, diagnosis of filarial infections largely depends upon
      detection of worms themselves, principally of microfilariae in blood or skin. In
      many infected people with lymphatic filariae, microfilariae (MF) are not
      detectable in blood, and removal of skin snips for detection of microfilariae in
      onchocerciasis seems a rather primitive technique. In addition, because the
      clinical manifestations of filariae vary greatly between individuals, an ideal
      diagnostic test would not only reveal individuals that are infected or have been
      exposed to infection, but would also differentiate between various clinical
      manifestations that the lymphatic-dwelling parasites, in particular, induce in
      the infected population. This is important because the pathological reactions
      induced following treatment with diethylcarbamazine vary with the clinical
      picture induced by the lymphatic filariae. They are certainly a major problem in
      onchocerciasis. Recent advances in biotechnology have started revolutionizing the
      diagnosis of filarial parasites not only in the host but also in their vectors.
      Monoclonal antibodies have been developed that are specific for detection of
      circulating antigens in lymphatic filariasis. Species-specific DNA probes have
      been developed for Brugia malayi, Wuchereria bancrofti, Onchocerca volvulus, and
      Loa loa. Diagnostic antigens have been obtained by cloning parasite DNA that
      codes for proteins recognized by infected individuals with only certain species
      of filariae. Recombinant antigens (rAgs) are available today which detect
      prepatent infections in onchocerciasis. Several laboratories developing new
      diagnostic tests for filariasis are currently evaluating these tests in the field
      with the collaboration of parasitologists, epidemiologists, and vector
      biologists.

PMID- 9279129
TI  - Regulatory role of cortisone and dietary carbohydrate energy in prepubertal rat
      mammary gland growth and development.
AB  - Role of cortisone and regulated carbohydrate energy in mammary gland growth,
      based on studies of morphometric and certain growth and energy related
      biochemical parameters has been evaluated in the adrenalectomized prepubertal
      female rat. Results showed improvement or restoration of mammary features like
      fat pad weight, area, duct system and sprouting of end and lateral buds by
      cortisone treatment from adrenalectomy induced suppressed state. Similarly the
      hormone rectified the gland nucleic acids, glycogen and rate of tissue oxidation
      of glucose levels, reduced under adrenalectomy. Adrenalectomy caused loss of
      appetite (33.5% less than normal intake). This amount of diet restriction to
      normal intact did not affect the gland morphology but reduced nucleic acids,
      protein, glycogen and glucose oxidation rate. Provision of dextrose mixed diet to
      the adrenalectomized rats showed variable improvements of these biochemical
      parameters except the gland protein level in association with increase in
      appetite. However, cortisone therapy under provision of dextrose supply, restored
      gland protein level and increased further in nucleic acids, glycogen and glucose
      oxidation rate. The morphological growth parameters with dextrose and cortisone
      also showed further improvements. Results suggested that glucocorticoid was
      essential mammary growth factor during prepubertal ages. The hormone appeared to
      operate via tissue metabolism and stimulating energy intake through appetite
      stimulation.

PMID- 9279130
TI  - Interrelationship between tumour virus receptors, A and C, coded by host cell
      genes in fowl.
AB  - Bryan Standard strain of Rous Sarcoma Virus (BS-RSV) of subgroup A and pseudotype
      of Bryan high titre RSV(RAV-49) of subgroup C and an equal mixture of subgroup A
      and subgroup C virus were inoculated to 11-day old embryos of white leghorn (WL),
      Australorp (AL) and f1 and f2 generations of crosses between WL and AL breeds of
      fowl to detect and estimate the interrelationship between tumour virus receptor
      coding host cell genes of tva and tvc loci. Linkage values estimated on a pooled
      sex basis were 0.08 +/- 0.03 and 0.10 +/- 0.03 for WL and AL breeds respectively
      and 0.09 on pooled breed basis. This clearly indicates that the tva and tvc loci
      are indeed closely linked in WL and AL breeds of fowl and supports the concept of
      using subgroup C virus to raise stocks resistant to subgroup A virus infection.

PMID- 9279131
TI  - Blackgram mottle virus RNA and its in vitro translation.
AB  - In vitro translation of blackgram mottle virus RNA in rabbit reticulocyte lysate
      resulted in synthesis of five major virus specific polypeptides with mol wt
      90,000(p90), 82,000(p82), 42,000(p42), 39,000(p39) and 32,000(p32), respectively.
      The polypeptide p39 was identified as coat protein based on its electrophoretic
      mobility and immunoprecipitation with BMoV-antiserum.

PMID- 9279132
TI  - Interrelationship of dietary lipids and ascorbic acid with hepatic enzymes of
      cholesterol metabolic pathway.
AB  - Effect of unsaturated and saturated fats on cholesterol metabolism was studied in
      ascorbate sufficient and deficient guineapigs. Experimental animals were made
      chronic ascorbic acid deficient by allowing oral intake of 0.5 mg ascorbic
      acid/day/animal. Elevation in serum and liver cholesterol and triglyceride along
      with depression in cholesterol oxidation and 7 alpha-hydroxylation in liver was
      observed in unsaturated fat fed guineapigs with ascorbate deficiency. Liver
      microsomal cytochrome P-450 level was found to be low in ascorbate deficient
      animals. Polyunsaturated fat intake could not lower the serum cholesterol level
      in ascorbate deficiency. Today polyunsaturated fat in the diet is encouraged all
      over the world for its hypocholesterolemic effect. This study indicates that
      polyunsaturated fat intake with ascorbic acid deficiency may produce
      hypercholesterolemia.

PMID- 9279133
TI  - Effect of inducers on hepatic microsomal mixed function oxidase system of male
      rats during food restriction.
AB  - Phenobarbital (PB; 80 mg/kg, ip) or 3-methylcholantrene (3-MC; 20 mg/kg, ip) was
      administered to Wistar male rats at the end of the feeding period of 30 days and
      the effects of food restriction (FR) and FR followed by inducer treatment on
      hepatic drug metabolizing enzymes, microsomal electron transport components,
      NADPH dependent lipid peroxidation and glutathione-s-transferase activities were
      studied. In both, PB and 3-MC treatment, the magnitude of increase in microsomal
      protein content, cytochrome b5 and aminopyrine N-demethylase (APND) activity was
      less in FR animals than in ad libitum fed; while cytochrome P-450 levels and
      activities of cytochrome c reductase and acetanilide hydroxylase (ACOH) were
      higher in FR animals. NADPH dependent lipid peroxidation and cytosolic
      glutathione-s-transferase activity were also enhanced due to PB and 3-MC
      treatment but the magnitude of increase was less in FR animals. The ACOH activity
      increased to a greater extent than APND activity in FR animals following PB and 3
      MC treatment. It is suggested that the response to inducers in the FR animals
      differ from that in the ad libitum fed rats.

PMID- 9279134
TI  - Protective effect of Liv.52 and Liv.100, ayurvedic formulations on lipid
      peroxidation in rat liver homogenate--an in vitro study.
AB  - Liv.100 is an improvised herbal formulation of Liv.52. Liv.52 is an important
      component of the ayurvedic system of medicine. This report highlights on the
      protective effect of Liv.52 and Liv.100 against in vitro peroxidation induced by
      hydrogen peroxide in rat liver homogenate. Addition of the two herbal
      formulations reduced the peroxidation effect of hydrogen peroxide in the dose-
      and time-dependent manner. The protective effect of the drugs is attributed to
      the enhanced supply of reduced glutathione that inhibit the deleterious process
      of lipid peroxidation. The results suggest on the antioxidant potential of Liv.52
      and Liv.100.

PMID- 9279135
TI  - An experimental model to produce partial thickness burn wound.
AB  - Simple burn wound models are always warranted. In view of this a partial
      thickness reproducible 2 degrees C burn wound has been produced using hot molten
      wax. This model is simple, convenient, and could be used to monitor wound
      contraction and epithelization in burn wounds.

PMID- 9279136
TI  - Optimization of test conditions for development of MTT as in vitro screen.
AB  - The quick and easy method of tetrazolium based colorimetric assay with MTT [3
      (4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] was used to test the
      viability of the adult parasites of a rodent filariid Acanthocheilonema viteae in
      vitro. The ideal conditions required for antifilarial screening were determined
      by correlating the MTT reduction ability of worms with their size and age in the
      vertebrate host, also the duration of incubation and temperature of the in vitro
      culture. It was observed that the worms collected from the host after 90 days of
      L3 (infective larvae) exposure were not suitable for in vitro screen as they
      could not reduce MTT to that extent as the worms of early infection. Healthy and
      full grown worms and also those incubated at 37 degrees C for 16 hr or more
      caused maximum MTT reduction. Thus, it is recommended to select healthy adult
      filariids of proper age and size (male > 3.5 cm; female > 7.0 cm). The incubation
      temperature of the in vitro culture system needs to be adjusted to 37 degrees C
      and parasites might be exposed to drugs upto 24 hr without much alteration in MTT
      reduction of untreated controls.

PMID- 9279137
TI  - Role of lipids in ethanol tolerance of Candida lambica.
AB  - Candida lambica with a moderate ethanol tolerance could grow in presence of
      ethanol up to 8% (v/v). In presence of increasing concentrations of ethanol,
      fatty acids were increased while phospholipids were decreased in lipid samples
      extracted from the organism. Supplementation of different lipids to the growth
      medium enabled the yeast to restore its growth in presence of 9% (v/v) ethanol.

PMID- 9279138
TI  - Cloning of PCR synthesized 191 bp DNA overlapping lac promoter for plasmid
      construction.
AB  - E coli genomic DNA was amplified by polymerase chain reaction (PCR) using two 5'
      and 3' oligonucleotide primers (27-mer). Amplified DNA was 191 bp. The region of
      amplified DNA on lac operon in E coli was 14 bp upstream from the transcription
      initiation site and 177 bp downstream. Amplified DNA was cloned into a phagemid
      vector for construction of plasmid, suitable for use as template for making
      strand-specific probe to detect initiated lac transcript by RNase protection
      assay, labelling for Southern and Northern hybridization. Another use of this
      probe made from this construct is to detect strand-specific DNA repair. The
      construct was verified by DNA sequencing.

PMID- 9279139
TI  - 66th Annual meeting of the Royal College of Physicians and Surgeons of Canada.
      Vancouver, British Columbia, September 25-28, 1997. Abstracts.

PMID- 9279140
TI  - 17th International Congress of Biochemistry and Molecular Biology in conjunction
      with 1997 annual meeting of the American Society for Biochemistry and Molecular
      Biology. San Francisco, California, August 24-29, 1997. Abstracts.

PMID- 9279141
TI  - Annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery
      Foundation, Inc. San Francisco, California, September 7-10, 1997. Abstracts.

PMID- 9279142
TI  - Recombinant human DNase (rhDNase) in cystic fibrosis: is it cost effective?

PMID- 9279143
TI  - Extensively and partially hydrolysed infant formulas for allergy prophylaxis.
AB  - The allergy preventive effect of extensively (N) and partially (PH) hydrolysed
      cows' milk formulas compared with a regular formula (RM) was assessed in 155
      infants with a family history of allergy. No cows' milk was given during the
      first nine months of life and no egg and fish up to 12 months of age. Breast
      feeding mothers avoided the same foods. At weaning the infants were randomised to
      one of the formula groups. The cumulative incidence of atopic symptoms at 18
      months was 51, 64, and 84% in the N, PH, and RM groups, respectively. From 6 to
      18 months there were significantly less cumulative atopic symptoms in the N group
      compared with the RM group, and significantly less than the PH group up to 6 (N =
      25%; PH = 46%) and 9 months (N = 34%, PH = 58%). At 9 months significantly fewer
      infants in the N group (10%) than in the PH group (33%) had a positive skin prick
      test to eggs. The findings support an allergy preventive effect of an extensively
      hydrolysed formula, but not of a partially hydrolysed formula, during the first
      18 months of life of high risk infants.

PMID- 9279145
TI  - Mutation analysis in 46 British and Irish patients with Gaucher's disease.
AB  - DNA from 46 unrelated patients with Gaucher's disease was analysed for 10 known
      mutations: 84GG(c84 G 85ins), N370S (c1226G), L444P (c1448C), R463C (c1504T),
      R496H (c1604A), IVS2+1, D409H (c1342C), RecNcil (c1448C-1498C), RecTL (c1342C
      1498C), and c1263del (c1264-1318del). Fifty four mutations (90%) were identified
      in 30 patients with type I disease. These included a previously undescribed
      recombinant mutation RecA456P (c1448C-1484C). Thirteen (54%) of 24 type II
      alleles were identified, including one new point mutation N462K (c1503G) and one
      new 55bp deletion also incorporating the RecTL mutations c1263del+RecTL (c1264del
      1498C). All four type III patients were homozygous for the L444P point mutation.
      Generally, patients with one copy of the N370S mutation had mild adult onset
      disease, regardless of the nature of their second mutation. Three exceptions had
      childhood onset disease and genotypes N370S/R463C, N370S/RecA456P, and N370S/?.
      The L444P/L444P genotype was thought to be associated with neurological disease.
      Two type I patients with this genotype who exhibited no central nervous system
      disease were identified, however. The R463C and c1263del mutations were found to
      be present at a higher frequency than reported in other populations and they
      should be included in any mutation screen of this population. The recombinant
      mutations RecA456P and c1263del+RecTL have not been previously described and are
      the fourth and fifth recombinant mutations identified in the glucocerebrosidase
      gene.

PMID- 9279144
TI  - Nitric oxide activity in childhood hypertension.
AB  - OBJECTIVES: To investigate nitric oxide (NO) activity in childhood hypertension
      using nitrite and nitrate (NOx) concentrations in plasma as an index of nitric
      oxide generation. DESIGN: Cross sectional study. SETTING: Tertiary care
      paediatric centre and district general hospitals in the UK. PATIENTS: Children
      attending the above centre for treatment of hypertension. The control subjects
      were normotensive healthy children attending district general hospitals for minor
      medical and surgical disorders. INTERVENTIONS: None. MAIN OUTCOME MEASURES:
      Plasma (P) and urinary (U) NOx concentrations, blood pressure, and glomerular
      filtration rate. RESULTS: Sixteen normal children (mean age 6.9 years), 13
      children with renovascular hypertension (mean age 7.8 years), and 25 children
      with hypertension associated with renal parenchymal disease (mean age 10.7 years)
      were studied. Mean (SD) PNOx values of children with hypertension with
      renovascular disease (15.3 (11.4) mumol/l) and renal parenchymal disease (18.3
      (11.4) mumol/l) were significantly above that of normal children (11.9 (5.9)
      mumol/l) after accounting for age and glomerular filtration rate influences.
      Higher concentrations of PNOx in normal children were associated with younger
      age, but not in the children with hypertension. Higher PNOx concentrations were
      also associated with a lower glomerular filtration rate in normal children and
      children with hypertension with renal parenchymal disease, but not in the
      children with hypertension with renovascular disease. UNOx excretion expressed as
      a ratio against urine creatinine (Ucreat) excretion was not statistically
      different among the study groups. CONCLUSIONS: PNOx is increased in children with
      hypertension even after statistical elimination of the glomerular filtration rate
      and age influences. This suggests a normal or increased NO synthase activity in
      childhood hypertension in contrast with adults with hypertension in whom it is
      described as reduced.

PMID- 9279146
TI  - The epidemic of SIDS in Norway 1967-93: changing effects of risk factors.
AB  - Time trends on the association of maternal age, birth order, and marital status
      with the risk of sudden infant death syndrome (SIDS) and non-SIDS deaths in
      Norway were analysed: 2356 postperinatal SIDS deaths and 4069 postperinatal non
      SIDS deaths were ascertained during 1967-93. The SIDS incidence was 1.25 per 1000
      in 1967, reached a peak of 2.69 in 1988, and fell to 1.22 in 1990 after the
      initiation of an intervention programme to avoid prone sleeping. In the entire
      period, young maternal age, high birth order, and unmarried motherhood were
      associated with SIDS. The adverse effects of young maternal age and high birth
      order increased continuously with time. From 1967-71 to 1990-93, the relative
      risk for maternal age < 20 years v maternal age 25-29 changed from 2.5 (95%
      confidence interval 2.0 to 3.2) to 7.0 (95% CI 4.2 to 11.9) (p < 0.0001), and for
      birth order 4+ nu birth order 1 from 3.2 (95% CI 2.5 to 4.2) to 14.4 (95% CI 8.3
      to 24.9) (p < 0.0001). Effects on non-SIDS deaths were far weaker and no secular
      trends were observed. The strong association of young maternal age, high birth
      order, and marital status in SIDS, but not in non-SIDS, provides evidence that
      SIDS is an epidemiological entity. The increasing effects of young maternal age
      and high birth order, which continued after the sudden drop in the SIDS rate in
      1990, suggest that further efforts to prevent SIDS should be aimed particularly
      at identifying causal mechanisms in high risk groups.

PMID- 9279147
TI  - Accidental injury: risk and preventative interventions.
AB  - OBJECTIVE: To evaluate the relation between risk factors for childhood
      unintentional injury and requests for injury prevention interventions as part of
      the Nottingham Safe at Home project, a primary care based controlled intervention
      study assessing the effectiveness of a package of injury prevention
      interventions. SETTING: 17 practices in Nottingham randomly selected from 55
      practices volunteering to take part in the study. METHODS: Postal questionnaire
      to all parents of children aged 3 to 12 months registered with the intervention
      practices (n = 1124) to assess risk factors for injury and to elicit requests for
      three injury prevention interventions: free home safety checks, low cost safety
      equipment, and free first aid training. RESULTS: 73% of parents responded to the
      questionnaire. The distribution of sociodemographic variables among responders
      was similar to that for the population of Nottingham. One third of parents (34%)
      requested one intervention, 21% requested two interventions, and 10% requested
      three. Receipt of means tested benefits, ethnicity, and residence in a deprived
      area were independently associated with requesting home safety checks. Non-owner
      occupation, lack of access to a car, receipt of means tested benefits, ethnicity,
      and unemployment were independently associated with requesting low cost safety
      equipment. Non-owner occupants were less likely to request first aid training.
      CONCLUSIONS: Families with risk factors for childhood unintentional injury do
      request home safety checks and low cost safety equipment, but they are less
      likely to request first aid training. Other methods for providing first aid
      advice may be needed to reach such families.

PMID- 9279148
TI  - Reduced levels of growth hormone, insulin-like growth factor-I and binding
      protein-3 in patients with shunted hydrocephalus.
AB  - OBJECTIVE: Children with hydrocephalus are characterised by slow linear growth in
      prepuberty, accelerated physical maturation during puberty, and reduced final
      height. We aimed to study the possible roles of growth hormone, insulin-like
      growth factor-I (IGF-I), and IGF binding protein-3 (IGFBP-3) in this growth
      pattern. STUDY DESIGN: One hundred and fourteen patients with shunted
      hydrocephalus (62 males) aged 5 to 20 years, of whom 17 had spina bifida (six
      males), and 73 healthy controls (38 males) were studied. Anthropometric measures,
      body mass index, and body fat mass were assessed and the stage of puberty was
      determined. Serum growth hormone and plasma IGF-I and IGFBP-3 concentrations were
      measured. RESULTS: The patients comprised 44 (26 males) who were prepubertal and
      70 (36 males) pubertal or postpubertal, while 32 of the controls (19 males) were
      prepubertal and 41 (19 males) pubertal or postpubertal. The prepubertal children
      with hydrocephalus had lower IGF-I (p = 0.002) and IGFBP-3 concentrations (p <
      0.001) than the controls, and the pubertal children had four times lower basal
      growth hormone concentrations (p < 0.001). There was a correlation between height
      SD score and IGF-I levels in the total patient population (r = 0.23; p = 0.01).
      Peripheral IGF-I concentrations peaked at pubertal stages 2-3 in the female
      patients and at stage 4 in the controls. The prepubertal patients on
      antiepileptic treatment, carbamazepine in most cases (73%), had higher IGF-I (p =
      0.01) and IGFBP-3 concentrations (p = 0.03) than those who had never been treated
      with antiepileptic drugs, but still lower IGFBP-3 levels than the controls (p =
      0.01). CONCLUSION: Based on these findings, it can be concluded that reduced
      growth hormone secretion may contribute to the pattern of slow linear growth and
      reduced final height observed in these patients.

PMID- 9279149
TI  - Diffusion weighted magnetic resonance imaging of compromised tissue in stroke.
AB  - Diffusion weighted imaging (DWI) and T2 weighted magnetic resonance imaging were
      performed on at least two occasions in 28 children presenting with stroke. In
      previous reports of DWI in human stroke, eventual infarction was observed (with
      only one exception) in all regions in which early DWI hyperintensity occurred. In
      the present report, two children had regions of DWI hyperintensity which did not
      progress to infarction. One patient who presented with right hemiplegia showed
      extensive high signal on DWI, with T2 evidence of tissue swelling but without
      hyperintensity. DWI changes persisted over weeks, with no imaging indication of
      infarction. This child recovered completely. A second child who had a major
      vessel infarct with concomitant regions of hyperintensity on T2 weighted imaging
      and DWI, also had DWI hyperintensity in an adjacent territory which did not
      develop any subsequent evidence of infarction. Thus in clinical practice DWI can
      demonstrate tissue which is compromised but not irreversibly so.

PMID- 9279150
TI  - Diagnosis of primary human herpesvirus 6 and 7 infections in febrile infants by
      polymerase chain reaction.
AB  - Primary human herpesvirus 6 (HHV-6) and 7 (HHV-7) infections were identified in
      febrile children by qualitative and quantitative polymerase chain reaction (PCR)
      assays. Diagnosis was based on the differential detection of viral DNA in
      peripheral blood mononuclear cells (PBMC), but not in saliva. Six of 41 febrile
      infants, but none of seven non-febrile controls, were identified with primary
      infections (three HHV-6, three HHV-7). These children had significantly higher
      viral loads in PBMC (HHV-6, median 24213 genomes/10(6) PBMC; HHV-7, median
      6,040,000 genomes/10(6) PBMC) than DNA-aemic, saliva PCR positive children (HHV
      6, median 1606 genomes/10(6) PBMC, p < 0.01; HHV-7, median 7089 genomes/ 10(6)
      PBMC, p < 0.05). Viral DNA was detected in serum by PCR in only 50% of primary
      infections. All three children with primary HHV-7 infection had febrile
      convulsions. Thus PCR, including quantitative assays, may identify primary HHV-6
      and HHV-7 infections when an appropriate combination of clinical specimens is
      used.

PMID- 9279152
TI  - Abnormal technetium labelled white cell scan in the colitis of chronic
      granulomatous disease.
AB  - A child with colitis was treated for Crohn's disease, diagnosed on history,
      clinical and colonoscopic findings, radiolabelled white cell bowel scan, and
      colonic histology. After septicaemia caused by an unusual organism, further
      investigation lead to a diagnosis of chronic granulomatous disease (CGD). The
      granulomatous colitis of CGD is clinically, histologically, and on white cell
      scanning, indistinguishable from that in Crohn's disease and should be considered
      in atypical cases. Infection with unusual 'pseudomonads' should prompt the
      exclusion of this disorder.

PMID- 9279151
TI  - Helicobacter pylori infection and growth delay in older children.
AB  - It is thought that Helicobacter pylori infection may influence growth rate in
      children. The aim of this study was to evaluate the prevalence of H pylori
      infection in healthy Italian children, and to look for differences in height
      between infected and non-infected subjects. Two hundred and sixteen children,
      aged 3 to 14 years, were tested for H pylori infection by 13C-urea breath test.
      Centile values for height were calculated. Composite indices for socioeconomic
      class and household crowding were also determined. Forty nine of 216 children
      (22.7%) were H pylori positive. The prevalence of infection increased with age.
      Eight of 49 H pylori positive children (16.3%) were below the 25th centile for
      height, compared with 13 of 167 H pylori negative children (7.8%). This
      difference became significant in children aged 8.5 to 14 years; in this group (n
      = 127), eight of 31 infected children (25.8%) were below the 25th centile for
      height, compared with eight of 96 non-infected children (8.3%). A significant
      correlation was found between socioeconomic conditions, household crowding, and H
      pylori status. By using stepwise logistic regression, only the centile value for
      height was significantly related to H pylori status in older children. Thus H
      pylori infection was associated with growth delay in older children, poor
      socioeconomic conditions, and household overcrowding. This finding is consistent
      with the hypothesis that H pylori infection is one of the environmental factors
      capable of affecting growth.

PMID- 9279153
TI  - SIDS: parental awareness and infant care practices in contrasting socioeconomic
      areas in Cardiff.
AB  - Parental awareness of risk factors for sudden infant death syndrome (SIDS) and
      infant care practices were compared in an area of relative deprivation and one of
      relative affluence in Cardiff. Awareness was high in both areas. More infants
      slept on the side in the deprived area (p < 0.02). One in three babies was
      exposed to cigarette smoking, significantly more in the deprived area (p <
      0.001). Health professionals should discourage side sleeping and smoking,
      especially in areas of deprivation.

PMID- 9279154
TI  - SIDS, illness, and acute medical care. New Zealand Cot Death Study Group.
AB  - One component of the Back to Sleep campaign to reduce the risk of sudden infant
      death syndrome (SIDS) is the recommendation that parents seek medical attention
      if their infant is unwell. The aim of this study was to investigate of SIDS could
      in part be explained by sick infants not getting appropriate medical care. Data
      on symptoms of illness and on acute medical contacts made for infants dying from
      SIDS (n = 390) within two weeks of their death were compared with those from a
      randomly selected group of control infants (n = 1592). SIDS cases had more severe
      illness than controls (odds ratio (OR) = 3.43; 95% confidence interval (CI) =
      1.69 to 5.38), and were more likely to have seen a general practitioner (OR =
      1.37; 95% CI = 1.09 to 1.73) or attended hospital (OR = 3.43, 95% CI = 1.09 to
      1.73). Only 1.3% of all SIDS cases had symptoms suggesting severe illness and had
      not seen a general practitioner. A lack of medical contacts in the two weeks
      before death does not contribute to the risk of SIDS.

PMID- 9279155
TI  - Pearson's syndrome without marrow involvement.
AB  - A child with a mitochondrial DNA deletion who presented with pancreatic exocrine
      insufficiency is reported. Though she developed many other features of Pearson's
      syndrome, there was no bone marrow involvement. Syndromes associated with
      mitochondrial DNA defects are highly variable and absence of one feature should
      not inhibit investigation.

PMID- 9279156
TI  - Central venous catheter use in UKCCSG oncology centres. United Kingdom Children's
      Cancer Study Group and the Paediatric Oncology Nursing Forum.
AB  - A cross sectional audit of central venous catheter (CVC) use was performed in
      United Kingdom Children's Cancer Study Group oncology centres. There were wide
      variations in choice of line, insertion technique, aftercare practice, and
      diagnosis of CVC related sepsis. These variations highlight the difficulty in
      interpretation of published data on CVC efficacy.

PMID- 9279157
TI  - Bone marrow trephine biopsy in infants. European Neuroblastoma Study Group.
AB  - Central review of bone marrow trephine biopsies obtained between January 1990 and
      July 1996 from 282 children with neuroblastoma showed that 18% of cores from
      older children and an unacceptably high 36% from infants were inadequate (p =
      0.0002). Centres should choose their operators for this invasive investigation of
      infants with more care in order to reduce the failure rate.

PMID- 9279158
TI  - Asthma--time for a change of name?

PMID- 9279159
TI  - Is fibrosing colonopathy an immune mediated disease?
AB  - Fibrosing colonopathy, a recently described complication of patients with cystic
      fibrosis, manifests clinically approximately 7-12 months after starting high dose
      pancreatic enzyme treatment. Although the pathogenesis of fibrosing colonopathy
      is unknown, it is highly correlated with pancreatic enzyme dose. In this study,
      immune mediated factors which may be associated with fibrosing colonopathy were
      explored. Sera from 14 patients with cystic fibrosis and meconium ileus were
      collected at diagnosis and then longitudinally for four to five years after
      enzyme treatment. Sera were analysed for total IgG and antiporcine trypsin IgG
      using an ELISA assay. Before enzyme treatment, serum antiporcine trypsin IgG
      concentrations were negligible, at 2.9 (SD 0.3) micrograms/ml. Thirteen patients
      (93%) developed a significant antibody response to porcine trypsin after starting
      enzyme treatment, reaching a peak concentration of 69.4 (20.1) micrograms/ml 7-12
      months after the introduction of enzymes. Since peak IgG concentrations coincided
      with published reports of time of onset of symptoms of fibrosing colonopathy,
      local injury by protease or by immune mediated mechanisms may be responsible for
      the pathological changes in this iatrogenic disease.

PMID- 9279160
TI  - Non-inflammatory musculoskeletal disorders in childhood.

PMID- 9279161
TI  - Imported malaria in children in the UK.

PMID- 9279163
TI  - A psychiatric perspective of epilepsy.

PMID- 9279162
TI  - Minor head injury.
AB  - Head injury is common in children, although the incidence of brain injury is much
      lower. Most children who sustain an injury to the head will only have a minor
      injury. Careful history, examination, and judicious use of radiology will
      identify those children at risk of brain injury. Children with no significant
      risk of brain injury may be safely discharged home to the care of responsible
      adults. Further work is needed to address sequelae after minor head injury.

PMID- 9279164
TI  - Polycystic ovary syndrome.

PMID- 9279165
TI  - Dental enamel defects and coeliac disease.

PMID- 9279166
TI  - Iridoplegia in severe Guillain-Barre syndrome.

PMID- 9279167
TI  - Predictive value of preschool surveillance in detecting learning difficulties.

PMID- 9279168
TI  - Bisphosphonates in osteogenesis imperfecta.

PMID- 9279169
TI  - White matter attenuation and megalencephaly.

PMID- 9279170
TI  - Salmonella meningitis acquired from pet snakes.

PMID- 9279171
TI  - Randomised controlled trials.

PMID- 9279172
TI  - Plasma E-selectin and ICAM-1 in acute Henoch-Schonlein purpura.

PMID- 9279173
TI  - Acquired rectovaginal fistulae in South Africa.

PMID- 9279174
TI  - Changing impact of fetal diagnosis of congenital heart disease.

PMID- 9279176
TI  - Randomised controlled trial of acetate in preterm neonates receiving parenteral
      nutrition.
AB  - AIMS: To determine whether by partly replacing chloride with acetate in
      parenteral nutrition, hyperchloraemia, metabolic acidosis, and the subsequent use
      of interventions such as colloid infusion, alkali treatment, increased assisted
      ventilation, would be reduced. METHODS: Fifty eight neonates of less than 32
      weeks gestation, receiving parenteral nutrition from days 3 to 10, were given
      either standard parenteral nutrition or a novel formulation with replacement of
      any chloride dose > 3 mmol/kg/day as acetate. RESULTS: Acetate (0 to 14.2
      mmol/kg/day) reduced the incidence of hyperchloraemia from 77% to 25%, and caused
      an increase in base excess from day 5 onwards (mean intergroup difference 3.6 to
      9.9 mmol/l), an increased pH (day 8, 7.34 vs 7.26), with an increased pCO2 (1
      kPa). The acetate group received less bicarbonate (median 0 mmol vs 4.8 mmol) and
      less colloid (41 ml/kg vs 204 ml/kg). There was no difference in any parameter of
      assisted ventilation. CONCLUSION: Acetate in neonatal parenteral nutrition
      reduces metabolic acidosis and hyperchloraemia.

PMID- 9279175
TI  - Randomised controlled trial of an aggressive nutritional regimen in sick very low
      birthweight infants.
AB  - AIMS: To improve energy intake in sick very low birthweight (VLBW) infants; to
      decrease growth problems, lessen pulmonary morbidity, shorten hospital stay, and
      avoid possible feeding related morbidity. Morbidity in VLBW infants thought to be
      associated with parenteral and enteral feeding includes bronchopulmonary
      dysplasia, necrotising enterocolitis, septicaemia, cholestasis and osteopenia of
      prematurity. METHODS: A prospective randomised controlled trial (RCT) comparing
      two types of nutritional intervention was performed involving 125 sick VLBW
      infants in the setting of a regional neonatal intensive care unit. Babies were
      randomly allocated to either an aggressive nutritional regimen (group A) or a
      control group (group B). Babies in group B received a conservative nutritional
      regimen while group A received a package of more aggressive parenteral and
      enteral nutrition. Statistical analysis was done using Student's t test, the Mann
      Whitney U test, the chi 2 test and logistic regression. RESULTS: There was an
      excess of sicker babies in group A, as measured by initial disease severity (P <
      0.01), but mean total energy intakes were significantly higher (P < 0.001) in
      group A at days 3 to 42 while receiving total or partial parenteral nutrition.
      Survival and the incidences of bronchopulmonary dysplasia, septicaemia,
      cholestasis, osteopenia and necrotising enterocolitis were similar in both
      groups. Growth in early life and at discharge from hospital was significantly
      better in babies in group A. There were no decreases in pulmonary morbidity or
      hospital stay. CONCLUSION: Nutritional intake in sick VLBW infants can be
      improved without increasing the risk of adverse clinical or metabolic sequelae.
      Improved nutritional intake resulted in better growth, both in discharge, but did
      not decrease pulmonary morbidity or shorten hospital stay.

PMID- 9279178
TI  - Doppler assessment of pulmonary artery pressure in neonates at risk of chronic
      lung disease.
AB  - AIM: To evaluate the pulmonary artery pressure (PAP) change in very low birth
      weight (VLBW) infants at risk of chronic lung disease (CLD). METHODS: The time to
      peak velocity:right ventricular ejection time (TPV:RVET) ratio calculated from
      the pulmonary artery Doppler waveform, which is inversely related to PAP, was
      used. The TPV:RVET ratio was corrected for different heart rate (TPV:RVET(c)).
      Seventy three VLBW infants studied on days 1, 2, 3, 7, 14, 21 and 28 were
      enrolled for the analysis. RESULTS: Twenty two infants developed CLD with a
      characteristic chest radiograph at day 28. Fifty one did not, of whom 17 were
      oxygen dependent on account of apnoea rather than respiratory disease, and 34
      were non-oxygen dependent. The TPV:RVET(c) ratio rose progressively in all three
      groups over the first three days of life, suggesting a fall in PAP. In the oxygen
      and non-oxygen dependent groups, the mean (SD) ratio rose to 0.53 (0.09) and 0.57
      (0.09), respectively, on day 7, then remained relatively constant thereafter. The
      CLD group rose more slowly after day 3 and had a significantly lower mean ratio
      from day 7 onwards compared with the other two groups (day 7: P < 0.001, days 14
      28: P < 0.0001), and fell significantly from 0.47 (0.11) on day 7 to 0.41 (0.07)
      on day 28 (P = 0.01), suggesting a progressive rise in PAP. The mean (SD) ratios
      at day 28 of all infants were: CLD group 0.41 (0.07); oxygen dependent group 0.66
      (0.15); and the non-oxygen group 0.67 (0.11). The CLD group had a significantly
      lower ratio than the oxygen dependent group and the non-oxygen group (P <
      0.0001). Using the TPV:RVET(c) ratio of < 0.46, infants at risk of developing CLD
      could be predicted on day 7 (predictive value 82.8%, sensitivity 54.5%,
      specificity 94.1%). CONCLUSION: The non-invasive assessment of PAP using the
      TPV:RVET(c) ratio may be useful in the longitudinal monitoring of PAP change in
      VLBW infants, and for prediction of chronic lung disease.

PMID- 9279179
TI  - Influence of respiratory distress syndrome on body composition after preterm
      birth.
AB  - AIM: To observe changes in body composition during the first week after birth, in
      preterm neonates with and without respiratory distress syndrome (RDS), so as to
      be able to provide optimal fluid and energy intake. METHODS: Twenty four babies
      with RDS and 19 healthy preterm babies, with gestational ages ranging from 26-36
      weeks, were studied daily for the first week after birth. Total body water (TBW)
      was measured using bioelectrical impedance analysis. The babies were weighed
      daily and a record made of fluid and energy intake. Body solids were calculated
      as the difference between body weight and TBW. RESULTS: There was a highly
      significant reduction in body weight by the end of the week, with the RDS babies
      losing more than the healthy babies (RDS 7.6%; non-RDS 3.7%). There was no
      significant difference in the amount of TBW at birth in the babies with and
      without RDS (RDS 85.1%; non-RDS 85.5%) and both groups lost the same amount of
      body water (RDS 10.9%; non-RDS 9.9%) by the end of the first week. The amount of
      total body water lost was unrelated to the volume of fluid administered. There
      was a loss of body solids during the first day in the RDS group, but, overall,
      there was a highly significant increase in both groups between birth and day 7,
      which was greater in the healthy babies (RDS 13.0%; non-RDS 42.7%). CONCLUSIONS:
      Loss of body water after birth occurs to the same extent in healthy preterm
      neonates and in babies with RDS and is unrelated to the volume of fluid
      administered. Given adequate nutritional support, an increase in body solids can
      accompany early postnatal weight loss and begins almost immediately after birth,
      in both healthy preterm babies and babies with RDS.

PMID- 9279177
TI  - Endothelial nitric oxide synthase in hypoxic newborn porcine pulmonary vessels.
AB  - AIMS: To determine if the failure of neonatal pulmonary arteries to dilate is due
      to a lack of nitric oxide synthase (NOS). METHODS: A monoclonal antibody to
      endothelial NOS was used to demonstrate the distribution and density of NOS in
      the developing porcine lung after a period in hypobaric hypoxia. Newborn piglets
      were made hypertensive by exposure to hypobaric hypoxia (50.8 kPa) from < 5
      minutes of age to 2.5 days of age, 3-6 days of age or 14-17 days of age. A
      semiquantitative scoring system was used to assess the distribution of
      endothelial NOS by light microscopy. RESULTS: NOS was present in the arteries in
      all hypoxic animals. However, hypoxia from birth caused a reduction in NOS
      compared with those lungs normal at birth and those normal at 3 days. Hypoxia
      from 3-6 days led to a high density of NOS compared with normal lungs at 6 days.
      Hypoxia from 14-17 days had little effect on the amount of NOS. On recovery in
      room air after exposure to hypoxia from birth there was a transient increase in
      endothelial NOS after three days of recovery, mirroring that seen at three days
      in normal animals. CONCLUSIONS: Suppression of NOS production in the first few
      days of life may contribute to pulmonary hypertension in neonates.

PMID- 9279180
TI  - Pulmonary function changes after nebulised and intravenous frusemide in
      ventilated premature infants.
AB  - AIMS: To compare the effects of a single dose of frusemide administered either
      intravenously or by nebulisation on pulmonary mechanics in premature infants with
      evolving chronic lung disease. METHODS: The effect of frusemide on pulmonary
      mechanics was studied at a median postnatal age of 23 (range 14-52) days in 19
      premature infants at 24 to 30 weeks gestational age, who had been dependent on
      mechanical ventilation since birth. Frusemide (1 mg/kg/body weight) was
      administered, in random order, intravenously and by nebulisation, on two separate
      occasions 24 hours apart. Pulmonary function studies were performed before and at
      30, 60, and 120 minutes after administration of frusemide. Urine was collected
      for six hours immediately before and for six hours after administration of
      frusemide. RESULTS: Nebulised frusemide increased the tidal volume 31 (SE 11.5)%
      and compliance 34 (SE 12)% after two hours, whereas no change in either was noted
      for up to two hours after intravenous frusemide administration. Neither
      intravenous nor nebulised frusemide had any effect on airway resistance. Six hour
      urine output increased from a mean (SE) of 3.3 (0.4) ml/kg/hour to 5.9 (0.8)
      ml/kg/hour following intravenous frusemide administration while nebulised
      frusemide had no effect on urine output. Urinary sodium, potassium, and chloride
      losses were also significantly higher after intravenous frusemide, whereas
      nebulised frusemide did not increase urinary electrolyte losses. CONCLUSION:
      Single dose nebulised frusemide improves pulmonary function in premature infants
      with evolving chronic lung disease without adverse effects on fluid and
      electrolyte balance.

PMID- 9279181
TI  - Echocardiographic assessment of patent ductus arteriosus shunt flow pattern in
      premature infants.
AB  - AIMS: To identify the patent ductus arteriosus (PDA) shunt flow pattern using
      Doppler echocardiography; and to assess whether it could be used to predict the
      development of clinically significant PDA. METHODS: Premature infants weighing
      under 1500 g, who required mechanical ventilation, and in whom daily
      echocardiography could be performed from day 1 until the ductus closed, and on
      day 7 to confirm closure, were studied. The PDA shunt flow was identified from
      four Doppler patterns, and the closed pattern of a closed duct was also
      presented. Clinically significant PDA was diagnosed when there was colour Doppler
      echocardiographic evidence of left to right ductal shunt associated with at least
      two of the following clinical signs: heart murmur (systolic or continuous);
      persistent tachycardia (heart rate > 160/min); hyperactive precordial pulsation;
      bounding pulses; and radiographic evidence of cardiomegaly or pulmonary
      congestion. RESULTS: Of 68 infants enrolled into this study, clinically
      significant PDA developed in 31. The most recordable sequence of transition
      change of shunt flow pattern for clinically significant PDA was: pulmonary
      hypertension pattern, to growing pattern, to pulsatile pattern, to closing
      pattern, to closed pattern. And that for non-clinically significant PDA was:
      pulmonary hypertension pattern, to closing pattern, to closed pattern. The
      growing and the pulsatile patterns were mostly documented in infants with
      clinically significant PDA. The first documented growing pattern to predict
      clinically significant PDA gave a sensitivity of 64.5% and a specificity of
      81.1%; the first documented pulsatile pattern gave a sensitivity of 93.5% and a
      specificity of 100%. CONCLUSION: Doppler echocardiographic assessment of PDA
      shunt flow pattern during the first 4 days of life is useful for predicting the
      development of clinically significant PDA in premature infants. At that stage,
      the closing or closed Doppler pattern indicates that infants are not at risk of
      developing clinically significant PDA; the growing or pulsatile Doppler pattern
      indicates a continuing risk of developing clinically significant PDA.

PMID- 9279182
TI  - Outcome of fetuses with heart disease diagnosed in utero.
AB  - OBJECTIVE: To review the outcomes of 193 fetuses with cardiac abnormalities
      detected by echocardiography. METHODS: A total of 422 fetuses between 16 and 41
      gestational weeks, referred to paediatric cardiologists for detailed
      echocardiography, were included in this study. RESULTS: Structural heart defects
      were found in 55 (28%), isolated arrhythmia in 105 (54%), and other non
      structural abnormalities (dilated cardiomyopathy, hypertrophic cardiomyopathy,
      aneurysm of the foramen ovale, isolated pericardial effusion or echogenic foci)
      in 33 (17%) of 193 fetuses. Total mortality was 26%. The prognosis was poor in
      fetuses with structural heart defects; 37 of 55 cases (67%) died in utero or
      postnatally. Chromosomal abnormality was associated with structural heart defect
      in 38% of fetuses, of whom 38% died. Among fetuses with isolated arrhythmia
      survival was 95%. Poor outcome was associated with complete heart block (n = 14)
      in 2 (14%) fetuses with hydrops and heart rate of less than 55 per minute, and
      with supraventricular tachycardia (n = 21) in three (14%) neonates delivered
      prematurely at a mean gestational age of 33 weeks. Furthermore, nine of 12
      fetuses (75%) with structural heart defects and arrhythmia died. Among fetuses
      with non-structural cardiac abnormalities, survival was 73%. Poor outcome was
      evident in fetuses with dilated cardiomyopathy in eight of 13 (62%) and with
      hypertrophic cardiomyopathy in one of eight (13%) of cases. CONCLUSIONS: Factors
      associated with a poor prognosis were: structural heart defect associated with
      chromosomal abnormality or arrhythmia, congestive heart failure associated with
      supraventricular tachycardia or complete heart block, especially if delivery
      occurs preterm; and fetal hydrops with congestive heart failure and
      atrioventricular valve regurgitation.

PMID- 9279183
TI  - Long-term hepatitis B vaccine in infants born to hepatitis B e antigen positive
      mothers.
AB  - Neonates of hepatitis B surface antigen (HBsAg) positive and hepatitis B encoded
      antigen (HBeAg) positive mothers received 10 micrograms of recombinant hepatitis
      B vaccine at months 0, 1, 6, or 0, 1, 2, 12, with or without immunoglobulin at
      birth, and were followed up to the age of 8 years for HBsAg, anti-HBc, and anti
      HBs. Some were boosted at month 60. The overall vaccine protection at month 12
      was 96.2%. No child became a chronic carrier beyond the age of 3 years, showing
      that this vaccine provides immediate protection against HBsAg carriage, and long
      term protection against fetally acquired HBsAg. After month 60 hepatitis B
      serological markers without disease, indicating re-exposure to HBV, reappeared in
      comparable numbers among boosted and non-boosted children (5 for a total of 167
      children). This vaccine provides long-term protection against hepatitis B chronic
      carriage and infection in high risk neonates with or without a month 60 booster.
      A booster at the age of 5-6 years or 11-12 years would reduce HBV infection,
      viral circulation and transmission, while ensuring long-term antibody
      persistence.

PMID- 9279184
TI  - Developmental pattern of 3-oxo-delta 4 bile acids in neonatal bile acid
      metabolism.
AB  - AIMS: To investigate whether a fetal pathway of bile acid synthesis persists in
      neonates and infants. METHODS: 3-oxo-delta 4 bile acids were determined
      qualitatively and quantitatively in the urine, meconium, and faeces of healthy
      neonates and infants, using gas chromatography-mass spectrometry. RESULTS: The
      mean percentage of 3-oxo-delta 4 bile acids in total bile acids in urine at birth
      was significantly higher than that at 3 or 7 days, and at 1 or 3 months of age.
      The concentration of this component in meconium was significantly higher than
      that in faeces at 7 days and at 1 or 3 months of age. CONCLUSIONS: The presence
      of large amounts of urinary 3-oxo-delta 4 bile acids may indicate immaturity in
      the activity of hepatic 3-oxo-delta 4-steroid 5 beta-reductase in the first week
      of postnatal life. Large amounts of this component in meconium may be due to the
      ingestion of amniotic fluid by the fetus during pregnancy.

PMID- 9279185
TI  - Indices of renal tubular function in perinatal asphyxia.
AB  - AIMS: To determine and compare two urinary indices of renal tubular function, N
      acetyl-glucosaminidase (NAG) and beta 2-microglobulin (beta 2 M), in healthy term
      neonates and babies with perinatal asphyxia. METHODS: In a prospective case
      control study using asphyxiated (n = 35) and normal control (n = 55) infants,
      urinary NAG and beta 2 M were assayed at 24-48 hours of life, 4-6 days, and 4-6
      weeks. RESULTS: NAG and beta 2 M were significantly increased at 24-48 hours and
      4-6 days in the asphyxiated infants compared with the controls. Increased NAG
      values reflect the degree of perinatal asphyxia more than do beta 2 M. Gentamicin
      also increased NAG excretion, but to a lesser extent than did perinatal asphyxia.
      CONCLUSIONS: NAG (+/- beta 2 M) may be a useful marker of perinatal asphyxia.
      Urinary NAG concentrations correlate with the severity of perinatal asphyxia.

PMID- 9279186
TI  - Use of methohexital for elective intubation in neonates.
AB  - The effectiveness and safety of a short acting barbiturate, methohexital, was
      assessed for its use at the time of elective intubation in 18 newborn infants
      with severe respiratory or cardiac conditions. Evaluation included the speed of
      action and the degree of relaxation, sedation, and sleep in the first five
      minutes after administration. All newborn infants were intubated in a fully
      relaxed and somnolent state. In most infants recovery was completed within five
      minutes. A slight to moderate oxygen saturation drop was observed during the
      period of intubation, especially in patients with cyanotic heart disease. The
      side effects of the drug were twitching and a slight drop in blood pressure. In
      conclusion, methohexital seems to be a useful drug for short term anaesthesia in
      neonates, during which, short procedures like elective intubation can be safely
      performed.

PMID- 9279187
TI  - Neonatal encephalopathy with a pungent body odour.
AB  - A neonate had transient unexplained bleeding into the gut, severe encephalopathy,
      and an abnormal pungent body odour. An inherited metabolic defect was excluded.
      The malodour was due to methanethiol and hydrogen sulphide, identified in urine.
      These sulphur compounds may have contributed to encephalopathy. Colonic bacteria
      were the probable source.

PMID- 9279188
TI  - Level of conus medullaris in term and preterm neonates.
AB  - AIMS: To compare the levels of conus medullaris in preterm and term neonates; to
      show the time of ascent to normal; and to evaluate the babies with low conus
      medullaris levels for tethered cord syndrome. METHODS: Levels were assessed using
      ultrasonography in 41 preterm and 64 term neonates. RESULTS: In the preterm group
      the conus medullaris level in one infant (2.4%) was below L4. In three infants
      (7.2%) it was between L2 and L3 and in 37 infants (90.4%) it was above L2. In the
      term group it was below L4 in one baby (1.6%), between L2 and L3 in four (6.3%),
      and above L2 in 57 babies (92.1%). The difference in the conus medullaris levels
      between term and preterm neonates and genders was not significant. Two patients,
      one with a conus medullaris level at L4-L5, and the other at L2-L3, had Down's
      syndrome. CONCLUSION: The ascent of conus medullaris seems to occur early in
      life. It is important to follow up patients with conus medullaris levels at or
      below the 4th lumbar vertebra for the development of tethered cord syndrome.

PMID- 9279189
TI  - Systematic review of prophylactic vs rescue surfactant.

PMID- 9279190
TI  - Avicenna (AD 980-1037) and Arabic perinatal medicine.

PMID- 9279191
TI  - Recent secular trends in multiple birth rates.

PMID- 9279192
TI  - Maternal and fetal infection with Mycobacterium tuberculosis.

PMID- 9279193
TI  - Surfactant abnormalities in infants with severe viral bronchiolitis.

PMID- 9279194
TI  - Hypoxic-ischaemic encephalopathy: MRI findings.

PMID- 9279195
TI  - New exanthematous disease with thrombocytopenia in neonates.

PMID- 9279196
TI  - 13C-urea breath test for Helicobacter pylori: cut-off point determination by
      cluster analysis.
AB  - 1. This study was performed on a large set of 13C-urea breath test results to
      determine the optimal cut-off point of the test for the diagnosis of Helicobacter
      pylori (Hp) infection. 2. The following steps were applied to three sets of urea
      breath test results obtained in three groups of subjects (696 adults before anti
      Hp treatment, 1056 adults after anti-Hp treatment and 173 children under 17 years
      of age): (1) demonstrate the distribution of urea breath test results as a mix of
      two normal populations (Hp negative and Hp positive) by logarithmic
      transformation of the results in each group of subjects; (2) apply statistical
      cluster analysis to determine the separation point between Hp-negative and 
      positive populations; (3) calculate the mean and SD of each population, and use
      these parameters in the equation of the normal distribution to establish the
      frequency curves of Hp-negative and -positive populations; and (4) determine the
      cut-off point of the urea breath test as the intersection of the two curves, and
      the risks of error related to it. 3. The optimal cut-off point was found at +3.00
      delta/1000, with a risk of false-negative or -positive response of the urea
      breath test of less than 3%. From this, a cut-off point of +3.00 delta/1000 for
      the 13C-urea breath test is recommended, with an indetermined zone between +2.5
      and +3.5 delta/1000 to account for the spontaneous variation of 13CO2 in breath
      and the limits of GC-isotope ratio-MS analytical precision.

PMID- 9279197
TI  - Clinical and haemodynamic sequelae of deep venous thrombosis: retrospective
      evaluation after 7-13 years.
AB  - 1. In contrast to the extensive documentation on diagnosis and treatment of deep
      venous thrombosis (DVT), information about long-term complications, like the post
      thrombotic syndrome (PTS), is scarce. Most studies report on clinical examination
      only, whereas adequate haemodynamic investigation is lacking. Therefore 81
      patients with venographically confirmed lower extremity DVT were clinically and
      haemodynamically reexamined 7-13 years after DVT (mean 10 years) to assess PTS.
      Interest was focused on the relation between clinical and haemodynamic PTS and
      the relation between location of the initial DVT and incidence of PTS. 2.
      Clinical signs and symptoms of PTS were classified according to the latest
      consensus of the international consensus committee on chronic venous disease. Non
      invasive venous vascular laboratory tests were performed to assess the venous
      outflow resistance and calf muscle pump function (CMP). CMP was determined by the
      supine venous pump function test (SVPT). 3. Clinically only 20 of 81 patients
      (25%) were asymptomatic, 34 (42%) had mild PTS (class 1-3), 25 (31%) moderate PTS
      (class 4) and 2 (2%) severe PTS (class 5-6); 57% had an abnormal CMP. Both the
      severity of clinical symptoms and the haemodynamic abnormalities were related to
      the location of the initial thrombus. Of the patients with distal DVT 11%
      developed moderate clinical PTS and 39% developed an abnormal CMP. CMP and
      difference in CMP between post-thrombotic and non-thrombotic leg were
      significantly related to the different classes of PTS. 4. This study indicates
      that 7-13 years after DVT 31% of the patients had moderate and 2% had severe
      clinical PTS, while 57% of the patients had abnormal haemodynamic findings (both
      related to the initial site of the thrombosis). Secondly, it reveals that the
      risk of PTS after distal DVT is not negligible, which causes concern about not
      diagnosing and treating patients with distal DVT. Thirdly, we have demonstrated
      that a functional test, such as the SVPT, is a sensitive test to assess post
      thrombotic damage. Therefore its use as a screening tool after a period of DVT
      should be investigated to select patients at risk of PTS.

PMID- 9279198
TI  - Changes in pulmonary venous return during head-up tilting in man.
AB  - 1. In a supine position, the heart fills to close to the limits of pericardial
      constraint and the pericardium may act to redistribute central blood volume from
      the left side of the heart back to the more compliant lung. 2. We probed whether,
      and through which mechanisms, a redistribution of blood from the lungs to the
      left heart occurs during vertical displacement and compensates for reduced venous
      return. 3. We investigated 16 normal volunteers with Doppler-echocardiography
      during 20 degrees, 40 degrees and 60 degrees head-up tilting. Tilting was stopped
      at 10 min in 10 subjects (group 1) and at 45 min in 6 subjects (group 2). 4. At
      10 min we observed a reduction in right ventricular diastolic dimension and left
      ventricular end-diastolic pressure, as estimated by the difference between the
      duration of the pulmonary venous flow during atrial contraction (Z wave) and that
      of the mitral A wave. We also recorded a decrease during systole (X wave) and an
      increase during diastole (Y wave) of the pulmonary venous forward flow velocity.
      These variations were evident at 20 degrees and became progressively greater with
      increasing degrees of tilting. In group 2, changes at 10 min and at 45 min for
      any degree of displacement were similar. 5. A decrease in right ventricular
      dimensions (ventricular interdependence) and underfilling of the lung compartment
      due to volume redistribution to the periphery (diminished lung contribution to
      pericardial constraint) augment compliance within the pericardial space, reduce
      downstream pressure for pulmonary venous return and move the pulmonary venous
      flow predominantly to ventricular diastole, allowing diastolic filling. 6. During
      head-up tilting a favourable interaction between heart and lungs increases
      compliance within the pericardial space and facilitates redistribution of blood
      from the lungs, resulting in a sustained compensation for the reduced venous
      return.

PMID- 9279199
TI  - Repeatability of spectral components of short-term blood pressure and heart rate
      variability during acute sympathetic activation in healthy young male subjects.
AB  - 1. Changes in the low-frequency (LF) components of blood pressure and heart rate
      variability and in the ratio of LF to high-frequency (HF) components of heart
      rate variability (LF/HF ratio) are used to assess acute changes in sympathetic
      control of blood pressure or heart rate and in sympathovagal balance that occur
      in response to physiological or pharmacological stimuli. Before these spectral
      indexes can be used to assess the effects of drug therapy or other clinical
      interventions on reflex sympathetic activity, their repeatability must be
      evaluated. 2. Intra-observer repeatability was studied by analysing changes in
      the LF components (expressed as absolute or normalized units) of cardiovascular
      variability and in the LF/HF ratio during sympathetic activation induced by
      nitroglycerin infusion (n = 10 subjects) or 60 degrees head-up tilt (n = 13
      subjects) repeated on two occasions, 2 days and 1 week apart respectively, in
      healthy young male volunteers. Repeatability was estimated as recommended by
      Bland and Altman. 3. Bland and Altman's plots of the repeatability of changes in
      the LF components and LF/HF ratio showed that measurements were sufficiently
      repeatable to be used over periods of time of up to 1 week in clinical studies.
      4. The sample-size tables derived from our results show that expression of
      spectral components as normalized units, and use of a cross-over design, minimize
      the number of subjects to be included in clinical studies conducted using similar
      designs and LF component changes as endpoints.

PMID- 9279200
TI  - Catamenial variations in erythrocyte sodium-lithium countertransport and blood
      pressure.
AB  - 1. We undertook a temporal study of external sodium-stimulated lithium efflux
      (sodium-lithium countertransport) in erythrocytes and blood pressure by measuring
      these two parameters in three phases of the menstrual cycle (menstrual, midcycle
      and luteal phases) in 22 healthy, non-medicated females with regular menstrual
      cycles. Plasma oestradiol and progesterone levels were also determined. 2. Sodium
      lithium countertransport activity (activity in 140 mmol/l external NaCl) in the
      midcycle phase (0.176 +/- 0.017 mmol h-1 l-1 of cells) was lower than in the
      menstrual (0.192 +/- 0.016 mmol h-1 l-1 of cells, P < 0.030) and luteal (0.203 +/
      0.018 mmol h-1 l-1 of cells, P < 0.030) phases. The Vmax of the transporter
      changed similarly but the K(m) was unaltered. 3. The plasma oestradiol level was
      628.9 +/- 39.1 pmol/l in the midcycle phase, higher than in the menstrual (232 +/
      18.5 pmol/l, P < 0.001) and luteal (372.5 +/- 28.1 pmol/l, P < 0.001) phases.
      The progesterone level was 28.6 +/- 2.1 nmol/l in the luteal phase, and values
      were lower in the menstrual (2.5 +/- 0.3 nmol/l, P < 0.001) and midcycle (2.8 +/-
      0.4 nmol/l, P < 0.001) phases. 4. There was no correlation between plasma
      oestradiol and sodium-lithium countertransport activity or Vmax during the
      menstrual cycle, but plasma progesterone was positively correlated with sodium
      lithium countertransport activity (r = 0.478, P < 0.025, n = 22) and Vmax (r =
      0.551, P < 0.045, n = 14) in the luteal phase. 5. Systolic blood pressure did not
      change significantly during the menstrual cycle. However, the diastolic pressure
      showed variation similar to that in sodium-lithium countertransport
      activity/Vmax, its midcycle value of 66.6 +/- 1.4 mmHg being lower than that in
      the luteal (71.6 +/- 1.3 mmHg, P < 0.025) and menstrual (70.6 +/- 1.4 mmHg, P <
      0.025) phases. 6. We conclude that sodium-lithium countertransport activity
      exhibits catamenial variation. Therefore we suggest, given this observation, that
      blood sampling for the assessment of the state of activity of the transport
      system be standardized in relation to a phase of the menstrual cycle in future
      studies involving females.

PMID- 9279201
TI  - Elevated plasma and urinary endothelin-I levels in human salt-sensitive
      hypertension.
AB  - 1. The behaviour of the potent vasoconstrictive endothelium-derived peptide
      endothelin-1 was evaluated in salt-sensitive hypertension. 2. Circulating and
      urinary endothelin-1 levels were evaluated in 30 men (mean age 44.6 +/- 3.1
      years) with uncomplicated essential hypertension after three consecutive 2-week
      periods on an intermediate (120 mmol), low (20 mmol) and high (240 mmol) NaCl
      diet. On the same occasions, blood pressure was measured to identify salt
      sensitive patients (n = 16), i.e. those patients showing a mean blood pressure
      increase > 10 mmHg when switching from a low to a high NaCl diet, and salt
      resistant patients (n = 14), i.e. those who did not show such mean blood-pressure
      variations. 3. Plasma endothelin-1 levels were higher (P < 0.005) in salt
      sensitive than in salt-resistant hypertensive patients after intermediate-, low-
      and high-NaCl diets. Urinary endothelin-1 excretion was similar in both groups
      after an intermediate-NaCl diet, whereas it was significantly higher in salt
      sensitive than in salt-resistant hypertensive subjects after low (P < 0.002) and
      high (P < 0.007) NaCl diets. High NaCl intake induced a significant increase in
      plasma endothelin-1 levels (P < 0.002) as compared with intermediate and low NaCl
      diet levels in salt-sensitive patients, but did not in salt-resistant subjects.
      No significant NaCl intake-related variations of urinary endothelin-1 excretion
      were observed in either group. 4. Salt-sensitive hypertensives are characterized
      by increased levels of endothelin-1 in both plasma and urine. This fact suggests
      that blood-pressure sensitivity to NaCl intake could be associated with an
      increased risk of developing both renal and cardiovascular damage.

PMID- 9279202
TI  - Inhibition of neutral endopeptidase, the degradative enzyme for natriuretic
      peptides, in rat kidney after oral SCH 42495.
AB  - 1. Inhibition of neutral endopeptidase (NEP), the degradative enzyme for atrial
      natriuretic peptide, was studied in vitro and in vivo using a previously
      characterized NEP inhibitor radioligand, 125I-labelled RB104. 2. SCH 42354, the
      active di-acid of the ethylester prodrug, SCH 42495, caused a concentration
      dependent displacement of 125I-labelled RB104 from rat renal NEP. The
      concentration of SCH 42354 that displaced 50% of radioligand bound to the enzyme
      NEP (IC50) was 3.3 +/- 0.1 nmol/l (mean +/- SEM). Enalaprilat, an angiotensin
      converting enzyme inhibitor, did not displace 125I-labelled RB104 in
      concentrations up to 10 mumol/l. 3. In adult normotensive Sprague-Dawley rats,
      oral SCH 42495 (3-300 mg/kg) caused significant inhibition of renal NEP (P <
      0.001). SCH 42495 had no effect on renal or plasma angiotensin converting enzyme
      activity, but high-dose SCH 42495 (300 mg/kg) caused a significant increase in
      plasma renin activity (P < 0.01). 4. In a time course study, oral SCH 42495 (30
      mg/kg) caused rapid (within 30 min) and significant inhibition of renal NEP for
      up to 48 h (P < 0.001). No changes in plasma atrial natriuretic peptide or plasma
      angiotensin converting enzyme activity were seen. 5. These data provide evidence
      that short-term administration of the NEP inhibitor SCH 42495 results in
      inhibition of renal NEP and does not inhibit the circulating or the tissue renin
      angiotensin system. The NEP inhibitor radioligand 125I-labelled RB104, is a
      useful tool to study tissue NEP inhibition after administration of NEP
      inhibitors.

PMID- 9279203
TI  - Reduction of placental nitric oxide synthase activity in pre-eclampsia.
AB  - 1. The role of the potent vasodilator nitric oxide in the pathogenesis of pre
      eclampsia is unclear. We have tested the hypothesis that placental activity of
      the enzyme which synthesizes nitric oxide (nitric oxide synthase) is reduced in
      pre-eclampsia. 2. Placentae were obtained after vaginal delivery or Caesarean
      section from women who had been assigned to the following groups according to
      standard obstetric criteria: term non-pre-eclamptic control, term pre-eclamptic,
      preterm non-pre-eclamptic control and preterm pre-eclamptic. Nitric oxide
      synthase activity of placental tissue homogenates was assessed by measuring
      conversion of [3H]L-arginine into [3H]L-citrulline in the presence of NADPH, FAD,
      tetrahydrobiopterin, calmodulin, CaCl2, magnesium acetate and a range of L
      arginine concentrations. Michaelis Menton constants (K(m)) amd maximum velocities
      of reaction (Vmax) were calculated using Lineweaver-Burk analysis. 3. Vmax was
      significantly reduced in both term and preterm pre-eclamptic placentae compared
      with placentae from corresponding gestation-matched controls. There were no
      significant differences in the K(m) values for nitric oxide synthase between any
      of the four groups, nor were Vmax or K(m) values significantly influenced by mode
      of delivery. 4. These results provide evidence that human placental nitric oxide
      synthase activity is significantly reduced in pre-eclampsia. Such a reduction was
      evident at both term and preterm gestations. Reduced placental nitric oxide
      synthase activity may have an adverse effect on placental haemodynamic function
      in pre-eclampsia, and could be involved in the pathogenesis of this important and
      common obstetric complication.

PMID- 9279204
TI  - Transport of L-arginine and the nitric oxide inhibitor NG-monomethyl-L-arginine
      in human erythrocytes in chronic renal failure.
AB  - 1. Transport of L-arginine and the nitric oxide synthase inhibitors NG-monomethyl
      L-arginine and NG-nitro-L-arginine was investigated in human erythrocytes from
      healthy donors and uraemic patients on haemodialysis. 2. Although K(m) values for
      total L-arginine influx were not significantly different in erythrocytes freshly
      isolated from controls or uraemic patients, uraemia was associated with an
      increase in the Vmax for transport (826 compared with 1176 mumol h-1 l-1 of
      cells) which was reduced to control values after dialysis. 3. Saturable influx of
      L-arginine was mediated by the classical cationic amino acid transport system y+
      and system y+L, known to transport cationic and neutral amino acids with higher
      affinity. 4. Under zero-trans conditions, the Vmax for L-arginine transport via
      system y+increased from 271 to 700 mumol h-1 l-1 of cells in uraemia, while K(m)
      values increased from 44 to 94 mumol/l. Dialysis had no significant effect on the
      kinetic parameters altered by uraemia. 5. Under zero-trans conditions, and with
      system y+ inhibited by N-ethylmaleimide (0.2 mmol/l), transport of L-arginine via
      system y+L was unaffected by uraemia. 6. Saturable influx of NG-monomethyl-L
      arginine was also mediated by systems y+ (K(m) = 56 mumol/l, Vmax = 353 mumol h-1
      l-1 of cells) and y+L (K(m) = 17 mumol/l, Vmax = 51.3 mumol h-1 l-1 of cells)
      and, as with L-arginine, uraemia increased the transport capacity for NG
      monomethyl-L-arginine. 7. Influx of the neutral nitric oxide synthase inhibitor
      NG-nitro-L-arginine was not readily saturable. 8. Intracellular concentrations of
      L-arginine and NG-monomethyl-L-arginine were significantly increased in
      erythrocytes from uraemic patients when compared with controls, consistent with
      an increased transport capacity for L-arginine and NG-monomethyl-L-arginine. 9.
      The present study provides evidence that system y+ mediates the increased
      transport of L-arginine and NG-monomethyl-L-arginine in human erythrocytes from
      patients with chronic renal failure. Our findings may have implications for the
      activity of the L-arginine-nitric oxide signalling pathway in vascular
      endothelial and smooth-muscle cells in uraemia.

PMID- 9279205
TI  - Protein degradation during renal passage in normal kidneys is inhibited in
      experimental albuminuria.
AB  - 1. Tritium labelled proteins, namely bovine serum albumin ([3H]BSA), rat serum
      albumin ([3H]RSA), anionic horseradish peroxidase ([3H]aHRP) and immunoglobulin
      present in urine fractions from rat filtration studies in vivo and isolated
      perfused rat kidneys (IPKs) have been shown by gel chromatographic analysis to be
      severely degraded to small peptides. The degradation of RSA and BSA in vivo has
      been shown to be similar. 2. Degradation of proteins in the urine from IPK
      experiments was inhibited by including 150 mmol/l lysine in the perfusate.
      Similarly, [3H]BSA and [3H]aHRP excreted from rats with puromycin aminonucleoside
      nephrosis was again essentially intact for both IPK and in vivo experiments. 3.
      It appears that the degradation of proteins observed in urine obtained from
      control kidneys is due, in part, to proteolytic activity associated with the
      proximal tubule. Inhibition of proximal tubule function, which occurs for both
      lysine and puromycin aminonucleoside treatments (as calibrated by lysozyme
      uptake), results in inhibition of the degradation observed. Glomerular epithelial
      cells could also contribute to the degradation. 4. There was no generation of low
      molecular-weight material in the perfusate or plasma arising from breakdown of
      circulating proteins or recycling of potential degradation products from the
      tubules.

PMID- 9279206
TI  - Determination of urea kinetics by isotope dilution with [13C]urea and gas
      chromatography-isotope ratio mass spectrometry (GC-IRMS) analysis.
AB  - 1. Stable urea isotopes can be used to study urea kinetics in humans. The use of
      stable urea isotopes for studying urea kinetic parameters in humans on a large
      scale is hampered by the high costs of the labelled material. We devised a urea
      dilution for measurement of the distribution volume, production rate and
      clearance of urea in healthy subjects and renal failure patients using the
      inexpensive single labelled [13C]urea isotope with subsequent analysis by
      headspace chromatography-isotope ratio MS (GC-IRMS) of the [13C]urea enrichment.
      2. The method involves measurement of the molar percentage excess of [13C]urea in
      plasma samples taken over a 4 h period after an intravenous bolus injection of
      [13C]urea. During the sample processing procedure, the plasma samples together
      with calibration samples containing a known molar percentage excess of [13C]urea
      are acidified with phosphoric acid to remove endogenous CO2, and are subsequently
      incubated with urease to convert the urea present in the plasma samples into CO2.
      The 13C enrichment of the generated CO2 is analysed by means of GC-IRMS. This
      method allows measurement of the molar percentage excess of [13C]urea to an
      accuracy of 0.02%. 3. Reproducibility studies showed that the sample processing
      procedure [within-run coefficient of variation (CV) < 2.8% and between-run CV <
      8.8%] and the GC-IRMS analysis (within-day CV < 1.3% and between-day CV < 1.3%)
      could be repeated with good reproducibility. 4. In clinical urea kinetic studies
      in a healthy subject and in a renal failure patient without residual renal
      function, reproducible values of the distribution volume, production rate and
      clearance of urea were determined using minimal amounts of [13C]urea (25-50 mg).
      5. Because only low [13C]urea enrichments are needed in this urea dilution method
      using GC-IRMS analysis, the costs of urea kinetic studies are reduced
      considerably, especially in patients with renal failure.

PMID- 9279207
TI  - Hepatic preservation with histidine-tryptophan-ketoglutarate solution in living
      related and cadaveric liver transplantation.
AB  - 1. Living-related liver transplantation has some advantages in the evaluation of
      novel clinical protocols, since many complicated factors affecting initial graft
      function are almost uniform in grafts obtained from healthy donors. 2. To compare
      histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW)
      solution in terms of tissue oxygenation in living-related liver transplantation,
      oxygen saturation of haemoglobin (SO2) in hepatic tissue and its heterogeneity
      (CV, coefficient of variation) were measured by near-infrared spectroscopy. The
      HTK and UW groups consisted of 15 and 49 successful transplants respectively, in
      which no statistical differences in background were observed. 3. In the HTK
      group, hepatic SO2 after portal vein reflow was higher (P < 0.01) than that in
      the UW group, as was that after hepatic artery reflow (P < 0.05). In the UW
      group, hepatic SO2 remained at the lower level at the end of the operation. 4.
      Furthermore, the increase in CV after portal vein reflow was normalized after
      hepatic artery reflow in the HTK group. However, the CV remained at a high level
      at the end of the operation in the UW group. 5. Postoperative peak aspartate
      aminotransferase level in the HTK group was lower than that in the UW group (P <
      0.05). 6. In cadaveric liver transplantation, higher hepatic SO2 and lower CV of
      hepatic SO2 in the early phase after reperfusion compared with the UW group (n =
      18) were also observed in the HTK group (n = 30) (P < 0.05). 7. In conclusion,
      recovery of tissue oxygenation and its heterogeneity after reperfusion in HTK
      preserved livers were more rapid and homogeneous than in UW-preserved livers in
      living-related liver transplantation. Accordingly, HTK solution may be a
      potential alternative to UW solution.

PMID- 9279208
TI  - Compound heterozygote for both rare apolipoprotein E1 (Gly127-->Asp, Arg158-
      >Cys) and E3(Cys112-->Arg, Arg251-->Gly) alleles in a multigeneration pedigree
      with hyperlipoproteinaemia.
AB  - 1. A French multigeneration pedigree with hyperlipoproteinaemia was investigated
      for the transmission of the rare apolipoprotein E1(Gly127-->Asp, Arg158-->Cys)
      variant. The proband, a 46-year-old male carrying the rare apoE1 variant,
      presented a severe type III hyperlipoproteinaemia like his three brothers and his
      sister. 2. ApoE phenotyping and genotyping showed a discrepancy in the second
      allele carried by the proband's wife and two of her children, thus suggesting
      another apoE gene mutation. Cloning and sequencing of the entire exon 4
      demonstrated a point mutation at codon 251, leading to an apoE3(Cys112-->Arg,
      Arg251-->Gly) allele. The proband's wife was normolipaemic and heterozygous for
      this rare isoform and the common apoE3 protein. The rare apoE3(Cys112-->Arg,
      Arg251-->Gly) allele has been transmitted to her two daughters. The first, aged
      19, was normolipaemic and heterozygous for this allele and the common apoE2
      allele. The second, carrying both the rare isoforms apoE1(Gly127-->Asp, Arg158-
      >Cys) and apoE3(Cys112-->Arg, Arg251-->Gly), presented a hypertriglyceridaemia at
      the age of 10. 3. The exploration of apoE status associated with plasma lipid
      levels and lipoprotein profiles in this three-generation pedigree made it
      possible to describe a compound heterozygote for two mutated alleles, one
      mutation being located in the N-terminal domain of the apoE protein and the other
      arising in the C-terminal domain.

PMID- 9279209
TI  - Oxidative stress in chronic obstructive pulmonary disease. Oxidative Stress Study
      Group.

PMID- 9279210
TI  - Expression of mRNA for gastrin-releasing peptide receptor by human bronchial
      epithelial cells. Association with prolonged tobacco exposure and responsiveness
      to bombesin-like peptides.
AB  - Bombesin-like peptides (BLPs) are important regulators of lung development and
      may also act as autocrine growth factors in lung tumors. We have previously
      demonstrated expression of mRNA for the three BLP receptor subtypes (neuromedin B
      [NMB]) receptor, gastrin-releasing peptide [GRP] receptor, and bombesin receptor
      subtype 3 [BRS-3]) in human non-small cell lung carcinoma (NSCLC) cell lines and
      bronchial biopsies using the reverse transcription-polymerase chain reaction (RT
      PCR; DeMichele, et al. Am. J. Respir. Cell Mol. Biol. 1994; 11:66-74). We have
      also previously found that growth responses to BLPs could be elicited in some,
      but not all, cultures of human bronchial epithelial (HBE) cells (Siegfried, et
      al. Anat. Rec. 1993; 236:241-247). In this report, we utilized RT-PCR to
      demonstrate mRNA expression of BLP receptor subtypes in cultured HBE cells and
      also assessed the response of these cultures to BLPs in proliferation assays. The
      pattern of mRNA expression was correlated with proliferative response, and the
      results were also analyzed in relation to smoking history and pulmonary function
      of the subjects studied. Our results suggest that expression of mRNA for the GRP
      receptor is associated with a long smoking history (> 25 pack-years [PY], p =
      0.02). This association was related to past tobacco exposure, regardless of
      whether the subjects were still active smokers at the time of tissue procurement.
      Responsiveness to GRP and NMB in proliferation assays was also found only in
      those HBE cultures with expression of mRNA for at least one of the known
      receptors for BLPs, and there was a significant association between expression of
      mRNA for the GRP receptor and proliferative response to both GRP and NMB (p =
      0.048). HBE cultures from subjects with a greater than 25 PY smoking history were
      also more likely to respond to BLPs in the proliferation assays than cells from
      subjects with less than a 25 PY history (10 of 16 versus 1 of 7, p = 0.06).
      Cultures of HBE cells from four of the five subjects with severe obstructive lung
      disease gave a positive response to GRP and NMB in proliferation assays, compared
      to five of fifteen without severe obstructive lung disease, but this difference
      was not significant (p = 0.13). These results suggest there is an increased
      likelihood of expression of the GRP receptor mRNA in the respiratory epithelium
      of some individuals with a history of prolonged tobacco exposure, and that
      expression of the GRP receptor mRNA is accompanied by responsiveness to the
      mitogenic effects of BLPs. These effects appear to persist after smoking
      cessation.

PMID- 9279211
TI  - Role for neurokinin-2 receptor in interleukin-5-induced airway
      hyperresponsiveness but not eosinophilia in guinea pigs.
AB  - In the guinea pig, interleukin-5 (IL-5) has been shown to induce airway
      hyperresponsiveness as well as eosinophilia, which are important symptoms in
      asthma. IL-5 seems to be a critical cytokine since it selectively affects
      eosinophil functions. The mechanism of action by which IL-5 leads to airway
      hyperresponsiveness may be important for our understanding of the pathogenesis of
      asthma. Neurogenic inflammation, which is mediated by nonadrenergic
      noncholinergic nerves (NANC), may play a role in the IL-5-induced effects in
      guinea pig airways. In this study, the role of neuropeptides in the IL-5-induced
      airway hyperresponsiveness and eosinophilia in the guinea pig was examined using
      selective neurokinin receptor antagonists. Intra-airway application of IL-5 (1
      microgram, twice) induces a selective eosinophil migration (control: 12 [8-22] x
      10(5) cells and IL-5: 90 [67-187] x 10(5) cells, p < 0.05) and activation
      (control: 6.3 +/- 0.9 ng eosinophil peroxidase [EPO]/ml bronchoalveolar lavage
      [BAL] fluid and IL-5: 29.3 +/- 4.9 ng EPO/ml BAL fluid, p < 0.05) and a
      pronounced airway hyperresponsiveness in vivo. The maximal responses to histamine
      are increased by 160 +/- 16% (p < 0.05) after IL-5. Treatment of guinea pigs with
      either the nonselective neurokinin (NK)-receptor antagonist, FK224, or the
      selective NK2-receptor antagonist, SR48968, results in a complete inhibition of
      the in vivo hyperresponsiveness found after application of IL-5. Vice versa,
      intra-airway administration of substance P (10 micrograms, twice) results in an
      airway hyperresponsiveness (increased maximal response after substance P: 166 +/-
      15% [p < 0.05]) without inducing migration or activation of eosinophils. All
      examined NK-receptor antagonists do not influence the IL-5-induced eosinophil
      accumulation. In addition, no effect of the NK-receptor antagonists is observed
      on the IL-5-induced eosinophil activation, as determined by BAL fluid EPO levels.
      The release of NK2-receptor active tachykinins plays an important role in the
      development of IL-5-induced airway hyperresponsiveness. This feature appears to
      be a step following eosinophil infiltration and activation since there are no
      effects on eosinophil function by pretreatment of the used NK-receptor
      antagonists.

PMID- 9279212
TI  - Lactoferrin, a potent tryptase inhibitor, abolishes late-phase airway responses
      in allergic sheep.
AB  - Tryptase, a serine protease released exclusively from activated mast cells, has
      been implicated as a potential causative agent in asthma. Enzymatically active
      tryptase is comprised of four subunits, and heparin stabilizes the associated
      tetramer. Lactoferrin, a cationic protein released from activated neutrophils,
      binds tightly to heparin, therefore we investigated lactoferrin as an inhibitor
      of tryptase and found that it is both a potent (Ki' is 24 nM) and selective
      inhibitor. Size exclusion chromatography studies revealed that lactoferrin
      disrupted the quaternary structure of active tryptase. Lactoferrin was tested in
      an allergic sheep model of asthma; aerosolized lactoferrin (10 mg in 3 ml
      phosphate-buffered saline, 0.5 h before as well as 4 and 24 h after inhalation
      challenge by Ascaris suum) abolished both late-phase bronchoconstriction (no
      significant increase in specific lung resistance 4 to 8 h following provocation,
      p < 0.05 versus vehicle treatment) and airway hyperresponsiveness (no detectable
      increase in airway sensitivity to carbachol challenge 24 h after antigen
      challenge, p < 0.05 versus vehicle). These data suggest tryptase involvement in
      both late-phase bronchoconstriction and airway hyperreactivity and furthermore
      suggest that a physiological function of neutrophil lactoferrin is the inhibition
      of tryptase released from mast cells.

PMID- 9279213
TI  - Endothelin-1-induced bronchoconstriction in asthma.
AB  - Endothelin-1 (ET-1) has been indirectly implicated in the pathophysiology of
      asthma, and it is a potent bronchoconstrictor both in vitro and by inhalation in
      animal models in vivo. We examined the effect of inhaled ET-1 on airway tone in
      comparison with methacholine in eight asthmatics and five healthy volunteers in a
      double-blind randomized fashion. After a screening methacholine challenge each
      asthmatic had two ET-1 (doubling dose range, 0.96 to 15.36 nmol) and one
      methacholine (doubling dose range, 0.33 to 21.0 mumol) challenge, and normal
      subjects had a single ET-1 challenge. Inhalations were delivered using a
      dosimeter, and lung function measurements were made using constant-volume body
      plethysmography, with end points being a 35% fall in specific airway conductance
      (SGaw) and a 15% fall in FEV1. Samples for plasma ET-1 were taken before and
      after the inhalations, and pulse, blood pressure and oxygen saturation were
      monitored throughout the inhalations. All the asthmatic subjects displayed rapid
      onset (< 5 min) dose-dependent bronchoconstriction to ET-1 across the dose range
      used, with mean (range) ET-1 PC35SGaw values of 5.15 (1.4 to 13.9) nmol, and 4.3
      (1.2 to 8.3) nmol for the two ET-1 inhalations, and 0.42 (0.2 to 0.7) mumol for
      methacholine. Albuterol completely and rapidly reversed ET-1-induced
      bronchoconstriction, and in two patients not given albuterol, bronchoconstriction
      lasted 60 to 90 min. No significant bronchoconstriction was observed in any of
      the healthy volunteers across the ET-1 dose range used (mean PC35SGaw > 15.36
      nmol). Oxygen saturation did not alter in either group, and plasma ET-1 did not
      change after ET-1 inhalation. Noninvasive blood pressure measurements revealed a
      fall in systolic blood pressure in normal subjects, with no change in asthmatics.
      Endothelin-1 is a potent bronchoconstrictor in asthma, with a bronchoconstrictor
      potency around 100 times that of methacholine in asthma. Asthmatics exhibit
      bronchial hyperreactivity to ET-1, and inhaled ET-1 can safely be given to
      asthmatics and normal subjects in the nebulized dose range 0.96 to 15.36 nmol.

PMID- 9279214
TI  - Acetylcholine via muscarinic receptors inhibits histamine release from human
      isolated bronchi.
AB  - Human bronchi were incubated in organ baths to measure histamine release. The
      calcium ionophore A23187 (10 mumol/L; 1 min) stimulated histamine release by 148
      +/- 28% (n = 11) above the prestimulation level but was ineffective in epithelium
      denuded bronchi. Neither bradykinin (0.1 mumol/L) nor compound 48/80 (10
      micrograms/ml) triggered the release of histamine from epithelium-intact bronchi.
      Acetylcholine did not affect spontaneous histamine release (about 2 nmol/g x 5
      min) but inhibited A23187-evoked histamine release in an atropine-sensitive
      manner. Already a concentration as low as 0.1 nmol/L acetylcholine was effective,
      the maximal inhibition (by 89%) occurred at 100 nmol/L, whereas a concentration
      of 10 mumol/L acetylcholine was ineffective. Oxotremorine (1 nmol/L), a stable
      agonist at muscarinic receptors, suppressed stimulated histamine release
      completely. Physostigmine (0.1 mumol/L), an acetylcholinesterase inhibitor,
      reduced A23187-evoked histamine release by 58%. Antihuman IgE antibody stimulated
      histamine release by 127 +/- 30% (n = 6) above the prestimulation level.
      Acetylcholine (100 nmol/L) inhibited also the immunologically evoked histamine
      release by 70%. In conclusion, the present experiments provide a model to
      characterize mast cells that are localized in or close to the airway surface
      epithelium. Acetylcholine via muscarinic receptors strongly inhibits the
      releasability of these mucosal mast cells being among the first cells to interact
      with inhaled antigens and environmental agents. The inhibitory action of
      physostigmine indicates the involvement of endogenous, probably non-neuronal
      acetylcholine expressed in airway epithelial cells.

PMID- 9279215
TI  - Quality control of peak flow meters for multicenter clinical trials. The Asthma
      Clinical Research Network (ACRN).
AB  - Although peak expiratory flow (PEF) measurements are recommended for monitoring
      and assessing treatment of asthmatic patients, and widely employed to assess
      outcome in clinical trials and epidemiologic studies, information about
      performance of peak flow meters (PFM) under field conditions is lacking. We
      describe a simple testing system consisting of a testing chamber, a spirometer,
      and a calibration syringe to evaluate the relative accuracy or median relative
      bias (MRB), precision, or inter-quartile range (IQR) of the mini-Wright PFM. The
      relative accuracy ranged from -4.4 to 13.2% (mean, 4.1%) and the precision from
      0.06 to 11.5% (mean, 1.2%). Durability of this PFM was assessed during a 26-wk
      clinical trial in 255 asthmatic subjects at five centers. Seventy-one PFM (19.9%)
      were identified as having failed to meet acceptance criteria, predominantly
      because of loss of relative accuracy, by the clinics at follow-up visits (n =
      36), and by the Data Coordinating Center on retrospective review of quality
      control measurements submitted by the clinics (n = 35). This study indicates that
      a simple device can be used to evaluate the relative accuracy and precision of a
      given PFM and to ensure the quality of PEF measurements during a clinical trial.
      To the extent that one can extrapolate these data to other devices, our findings
      indicate that the failure rate of PFM over time can be high, indicating that
      quality control of a PFM over time is absolutely essential in clinical trials as
      well as in routine clinical care.

PMID- 9279216
TI  - Asymptomatic airway hyperresponsiveness: a three-year follow-up.
AB  - The physiopathology and significance of asymptomatic airway hyperresponsiveness
      (AHR) are still to be defined. Over a 3-yr period, we compared clinical,
      immunologic, and physiologic features of 30 subjects who had asymptomatic AHR
      with those of 30 symptomatic asthmatic subjects and 30 normoresponder subjects
      (age: 31.9 +/- 1.4 yr [mean +/- SEM]; n = 90). Each subject completed a
      respiratory questionnaire and underwent spirometry, measurement of bronchodilator
      response and peak expiratory flows, an allergy skin-prick test, blood eosinophil
      count, assay for total serum IgE level, and methacholine challenge. These tests
      were repeated annually, at the same period of the year, for 3 yr. Subjects with
      asymptomatic AHR had greater bronchodilator responses (p = 0.001), variability of
      peak expiratory flow rate (PEFR) (p = 0.02), and prevalence of atopy (p = 0.02)
      than did the normoreactive subjects. Compared with asthmatic subjects, subjects
      with asymptomatic AHR had a lower blood eosinophil count (p = 0.004), higher mean
      FEV1 (p = 0.006), and weaker bronchodilator response (p = 0.02), but an even
      greater perception of bronchoconstriction (p < 0.001). After 3 yr, the
      concentration of methacholine provoking a 20% decrease in FEV1 (PC20) had
      decreased significantly in the asymptomatic AHR subjects (p < 0.0001) as compared
      with the other two groups, and of the 28 subjects studied at this time, four
      (14.3%) had developed asthma symptoms. These last four subjects were atopic and
      exposed to animals when they developed asthma, had a familial history of asthma,
      and had an increased baseline AHR as compared with the subjects who did not
      develop symptoms. In conclusion, this study shows that over a 3-yr period,
      subjects with asymptomatic AHR had a greater increase in airway responsiveness
      and frequency of development of asthma symptoms than did normoresponsive
      subjects. Allergen exposure in sensitized subjects at the time of the study, and
      genetic predisposition, seemed the main risk factors for the development of
      symptomatic asthma in this population.

PMID- 9279217
TI  - Positive human health effects of dust suppression with canola oil in swine barns.
AB  - A crossover trial was conducted to evaluate the acute human health effects of a
      dust control technology in a swine confinement facility. Twenty lifetime
      nonsmoking male subjects, with no evidence of allergy or asthma and no previous
      swine barn exposure, participated in the study, which included a laboratory
      session (baseline), 5-h exposure in a swine room sprinkled with canola oil
      (treatment) and 5-h exposure in a traditional swine room (control). Mean values
      of inhalable dust concentrations and endotoxin levels in the control room were
      significantly greater than those observed in the treatment room. Mean shift
      changes in FEV1 from preexposure to end of exposure were 1.1% (standard error,
      0.63%) on baseline day, -1.9% (0.63%) on treatment day, and -9.9% (1.12%) on
      control day; the differences in the shift changes were statistically significant.
      Mean value of methacholine concentration that reduced the FEV1 by 20% (PC20) in
      bronchoprovocation tests on baseline day was significantly different from that on
      treatment day (p = 0.04) and that on control day (p < 0.001). Significant
      increases were also observed in white blood cell counts and nasal lavage cell
      counts on the control day in comparison with the other two days. Blood neutrophil
      counts after control room exposure were twice those observed on baseline and
      after exposure to the treatment room. Significant differences were also observed
      in IL-1 beta, IL-6, and IL-8 nasal lavage cytokines and in IL-6 serum cytokine.
      These results suggest that the canola oil dust control method is effective in
      improving indoor air quality in swine barns and reducing acute health effects in
      naive healthy subjects.

PMID- 9279218
TI  - The inflammatory effects of 2 ppm NO2 on the airways of healthy subjects.
AB  - Nitrogen dioxide (NO2) is a free radical and a common oxidant in polluted air.
      Here we present data on the time course of inflammation after NO2 exposure, as
      reflected in bronchial biopsy and airway lavage specimens. Healthy, nonsmoking
      subjects were exposed to air or 2 ppm NO2 for 4 h in random order on separate
      occasions. Endobronchial biopsies, bronchial washing (BW), and bronchoalveolar
      lavage (BAL) were done at 1.5 h (n = 15) or 6 h (n = 15) after exposure. In BW,
      exposure to NO2 induced a 1.5-fold increase in interleukin-8 (IL-8) (p < 0.05) at
      1.5 h and a 2.5-fold increase in neutrophils (p < 0.01) at 6 h. In BAL fluid
      (BALF), small increases were observed in CD45RO+ lymphocytes, B-cells, and
      natural killer (NK) cells only. Immunohistologic examination of bronchial biopsy
      specimens showed no signs of upregulation of adhesion molecules, and failed to
      reveal any significant changes in inflammatory cells at either time point after
      NO2 exposure. In summary, NO2 induced a neutrophilic inflammation in the airways
      that was detectable in BW at 6 h after NO2 exposure. The increase in neutrophils
      could be related to the enhanced IL-8 secretion observed at 1.5 h after exposure.
      The absence of adhesion-molecule upregulation or cellular inflammation in mucosal
      biopsy specimens indicates that the major site of inflammation following exposure
      to NO2 may be in the smaller airways and not in the alveoli.

PMID- 9279219
TI  - Nebulized glutathione induces bronchoconstriction in patients with mild asthma.
AB  - To assess the effects on bronchial responsiveness of nebulized glutathione (GSH),
      one of the most efficient scavengers of oxidant substances in the airways, we
      studied eight patients with mild asthma (FEV1, 88 +/- 11% predicted [SD]) in a
      randomized, double-blind, cross-over, placebo-controlled fashion. Bronchial
      challenge was measured using both FEV1 and total pulmonary resistance (Rrs) by
      the forced oscillation technique. Patients received nebulized GSH (600 mg with 4
      ml of 0.9% sodium chloride) or placebo (identical saline solution) over a period
      of 25 min, 1 wk apart. Placebo provoked subclinical mild bronchoconstriction
      (changes from baseline: FEV1, -1%; Rrs, +17%); by contrast, GSH caused major
      airway narrowing (changes from baseline: FEV1, -19%; Rrs, +61%) and induced cough
      (four patients) or breathlessness (three patients). Differences between placebo
      and GSH after challenge were also noticeable in both FEV1 (p = 0.03) and Rrs (p =
      0.02). Neither osmolarity (660 mosm.kg-1) nor pH (3.0) of the GSH solution
      accounted for these effects. Nebulized salbutamol (5.0 mg) given before the GSH
      challenge blocked GSH-induced bronchoconstriction. Furthermore, GSH-induced FEV1
      falls were inversely correlated with metabisulfite bronchoprovocation
      (provocative dose [PD20], 1.49 +/- 1.83 mumol) but not with methacholine
      challenge. The detrimental effects of nebulized GSH on the airway bronchial tone
      in patients with mild asthma strongly suggests bronchoconstriction provoked by
      sulfite formation.

PMID- 9279220
TI  - Soluble E-selectin levels in sepsis and critical illness. Correlation with
      infection and hemodynamic dysfunction.
AB  - E-selectin, an early mediator of leukocyte-endothelial adhesion, is expressed on
      activated endothelium. Soluble E-selectin is present in the supernatant of
      cytokine-activated endothelial cells and elevated serum levels are found in a
      variety of inflammatory conditions. We documented elevated E-selectin serum
      levels in 119 critically ill medical ICU patients (log transformed mean E
      selectin level, measured by ELISA, was 5.28 ng/ml) compared to normal volunteers
      (1 ng/ml). Forty-three patients with culture-positive sepsis had higher (p <
      0.05) E-selectin levels (15.39 ng/ml) than 24 patients with culture-negative
      sepsis (4.87 ng/ml), 44 with noninfectious SIRS (2.33 ng/ml), and eight without
      SIRS (1.97 ng/ml). E-selectin levels related strongly to the degree of
      hemodynamic compromise (p < 0.0001). Further analysis demonstrated
      microbiological status and hemodynamic status to be independent variables related
      to E-selectin level. Day 1 E-selectin levels correlated positively with peak
      organ failure score over the course of ICU hospitalization (r = 0.30, p = 0.001)
      and were higher (p < 0.05) for nonsurvivor (10.61 ng/ml, n = 26) than survivors
      (4.35 ng/ml, n = 93). We conclude that soluble E-selectin levels are higher in
      serum of patients with microbiologically documented sepsis than in other
      critically ill medical ICU patients. Day 1 E-selectin levels correlate highly
      with hemodynamic compromise and modestly with subsequent organ dysfunction and
      survival.

PMID- 9279221
TI  - Dobutamine increases alveolar liquid clearance in ventilated rats by beta-2
      receptor stimulation.
AB  - Although it is well known that beta-adrenergic agonist stimulation increases
      alveolar epithelial sodium and fluid transport, it is not known whether the beta
      1 or the beta-2 receptor mediates this effect. Two clinically relevant beta
      adrenergic agonists, dopamine (beta-1 agonist) and dobutamine (beta-1 and beta-2
      agonist) were used to define the contribution of these two beta-receptors to beta
      adrenergic stimulated fluid clearance from the air spaces of the lungs. Alveolar
      fluid clearance was measured in anesthetized, ventilated rats over one hour after
      instilling an isosmolar 5% albumin solution in Ringer's lactate with 3 microCi
      125I-albumin. The concentrations of the labeled and unlabeled albumin were used
      to quantify alveolar liquid clearance. Dopamine, whether given intra-alveolar
      (10(-4) M) or intravenously (5-10 micrograms/kg/min), had no effect. However,
      both intra-alveolar (10(-4) M) and intravenous (5 micrograms/kg/min) dobutamine
      increased alveolar liquid clearance by approximately 50% over one hour compared
      to controls. ICI 118,551, a potent and specific beta-2 antagonist, blocked the
      effect of dobutamine. The dobutamine effect was blocked by amiloride (10(-3) M),
      an inhibitor of sodium uptake. In summary, the beta-2 receptor mediates beta
      adrenergic stimulation of alveolar epithelial sodium and fluid transport.

PMID- 9279222
TI  - Ultrasonic nebulization for efficient delivery of surfactant in a model of acute
      lung injury. Impact on gas exchange.
AB  - We investigated the effect of ultrasonic nebulization versus instillation of
      exogenous surfactant on gas exchange abnormalities provoked by detergent
      inhalation in perfused rabbit lungs. Ventilation-perfusion (VA/Q) distribution
      was assessed by the multiple inert gas elimination technique. For nebulization of
      natural bovine surfactant (Alveofact), an ultrasonic device was placed in line
      with the inspiratory gas flow tubing, manufacturing particles with a mass median
      aerodynamic diameter of approximately 4.5 microM and high aerosol concentration.
      In vitro studies demonstrated biochemical and biophysical integrity of
      postnebulization surfactant. Lung aerosol deposition was monitored by a laser
      photometric technique. In lungs with sham inhalation of saline, tracheal
      instillation of surfactant (approximately 11 mg/kg body weight, infused over 50
      min) provoked substantial VA/Q mismatch and limited shunt flow, whereas lung
      surfactant deposition by ultrasonic nebulization (approximately 7 to 9 mg/kg body
      weight; nebulization time, 50 min) did not interfere with physiologic gas
      exchange. Tween 20 inhalation provoked severe VA/Q mismatch with predominant
      shunt-flow (approximately 21%). This was not reversed by "rescue" application of
      instilled surfactant, but largely reversed by nebulized surfactant (shunt reduced
      to 5.5%; p < 0.01). Analysis of postaerosol lavage fluid demonstrated partial
      reconstitution of surface activity by nebulized surfactant. We conclude that
      ultrasonic nebulization may be employed for efficient delivery of functionally
      intact natural surfactant to the distal bronchoalveolar space. This approach
      effects rapid improvement of gas exchange in a model of acute homogeneous lung
      injury.

PMID- 9279223
TI  - Effects of various timings and concentrations of inhaled nitric oxide in lung
      ischemia-reperfusion. The Paris-Sud University Lung Transplantation Group.
AB  - Experimental studies reveal that inhaled nitric oxide (NO) can prevent, worsen,
      or have no effect on lung injury in the setting of ischemia-reperfusion (I-R). We
      tested the hypothesis that these disparate effects could be related to
      differences in the timing of administration and/or concentration of inhaled NO
      during I-R. Isolated rat lungs were subjected to 1-h periods of ischemia followed
      by 1-h periods of blood reperfusion. We investigated the effects of NO (30 ppm)
      given during ischemia, NO (30 or 80 ppm) begun immediately at reperfusion, or NO
      (30 ppm) given 15 min after the beginning of reperfusion, on total pulmonary
      vascular resistance (PVR), the coefficient of filtration (Kfc), the lung wet/dry
      weight ratio (W/D) of lung tissue, and lung myeloperoxidase activity (MPO). A
      control group did not receive NO. NO given during ischemia had no effect on Kfc
      or MPO, but decreased PVR. NO (30 ppm) during reperfusion (early or delayed)
      decreased PVR, W/D, Kfc and MPO. NO at 80 ppm decreased PVR and MPO but not W/D
      or Kfc. In conclusion, NO at 30 ppm, given immediately or in a delayed fashion
      during reperfusion, attenuates I-R-induced lung injury. NO at 30 ppm given during
      ischemia or at 80 ppm during reperfusion is not protective.

PMID- 9279224
TI  - Extubation outcome after spontaneous breathing trials with T-tube or pressure
      support ventilation. The Spanish Lung Failure Collaborative Group.
AB  - A 2-h T-tube trial of spontaneous breathing was used in selecting patients ready
      for extubation and discontinuation of mechanical ventilation. However, some doubt
      remains as to whether it is the most appropriate method of performing a
      spontaneous breathing trial. We carried out a prospective, randomized,
      multicenter study involving patients who had received mechanical ventilation for
      more than 48 h and who were considered by their physicians to be ready for
      weaning according to clinical criteria and standard weaning parameters. Patients
      were randomly assigned to undergo a 2-h trial of spontaneous breathing in one of
      two ways: with a T-tube system or with pressure support ventilation of 7 cm H2O.
      If a patient had signs of poor tolerance at any time during the trial, mechanical
      ventilation was reinstituted. Patients without these features at the end of the
      trial were extubated. Of the 246 patients assigned to the T-tube group, 192
      successfully completed the trial and were extubated; 36 of them required
      reintubation. Of the 238 patients in the group receiving pressure support
      ventilation, 205 were extubated and 38 of them required reintubation. The
      percentage of patients who remained extubated after 48 h was not different
      between the two groups (63% T-tube, 70% pressure support ventilation, p = 0.14).
      The percentage of patients falling the trial was significantly higher when the T
      tube was used (22 versus 14%, p = 0.03). Clinical evolution during the trial was
      not different in patients reintubated and successfully extubated. ICU mortality
      among reintubated patients was significantly higher than in successfully
      extubated patients (27 versus 2.6%, p < 0.001). Spontaneous breathing trials with
      pressure support or T-tube are suitable methods for successful discontinuation of
      ventilator support in patients without problems to resume spontaneous breathing.

PMID- 9279225
TI  - Mechanical ventilation with or without daily changes of in-line suction
      catheters.
AB  - The purpose of this study was to determine the safety and cost-effectiveness of
      not routinely changing in-line suction catheters for patients requiring
      mechanical ventilation. Patients were randomly assigned to receive either no
      routine in-line suction catheter changes (n = 258) or in-line suction catheter
      changes every 24 h (n = 263). The main outcome measure was the incidence of
      ventilator-associated pneumonia. Other outcomes evaluated included hospital
      mortality, acquired organ system derangements, duration of mechanical
      ventilation, lengths of intensive care and hospital stay, and the cost for in
      line suction catheters. Ventilator-associated pneumonia was seen in 38 patients
      (14.7%) receiving no routine in-line suction catheter changes and in 39 patients
      (14.8%) receiving in-line suction catheter changes every 24 h (relative risk,
      0.99; 95% CI, 0.66 to 1.50). No statistically significant differences for
      hospital mortality, lengths of stay, the number of acquired organ system
      derangements, death in patients with ventilator-associated pneumonia, or
      mortality directly attributed to ventilator-associated pneumonia were found
      between the two treatment groups. Patients receiving in-line suction catheter
      changes every 24 h had 1,224 catheter changes costing a total of $11,016;
      patients receiving no routine in-line suction catheter changes had a total of 93
      catheter changes costing $837. Our findings suggest that the elimination of
      routine in-line suction catheter changes is safe and can reduce the costs
      associated with providing mechanical ventilation.

PMID- 9279226
TI  - Effect of 48 hours of nitric oxide inhalation on pulmonary vasoreactivity in
      rats.
AB  - Nitric oxide (NO) has been shown to down regulate its own synthesis in vitro. We
      tested the hypothesis that NO inhalation (30 ppm under normoxic conditions) could
      decrease the release of endogenous endothelial NO, and thus alter pulmonary
      vasoreactivity. Pulmonary vasoreactivity was assessed in isolated perfused rat
      lungs immediately or 6 h after a 48 h NO inhalation period, and compared with a
      control group. NO inhalation resulted in an increase in pulmonary vasoconstrictor
      reactivity to angiotensine II and U-46619, a reduction in the potentiation by the
      eNOS inhibitor L-NAME of the angiotensine II response, a decrease in endothelium
      dependent vasodilation to arginine vasopressin, whereas non-endothelium-dependent
      vasodilation to sodium nitroprusside remained unaltered. These alterations
      returned to control values in the group studied 6 h after the end of NO
      inhalation, and were not prevented by inhibition of the prostanoid synthesis, or
      by pretreatment with the endothelin receptors antagonist Bosentan. These results
      indicate that NO inhalation over 2 d induces a reversible alteration of pulmonary
      vasoreactivity in relationship with a decrease in endogenous NO release.
      Inhibition of eNOS could be involved.

PMID- 9279227
TI  - Dilatory effect of furosemide on rat tracheal arterioles and venules.
AB  - Furosemide pretreatment greatly reduces the severity of an asthmatic response to
      several types of bronchoconstrictor challenge. Indirect evidence suggests that
      furosemide exerts its protective effects by dilating the airway vasculature
      during thermal stress. To test the hypothesis that furosemide dilates airway
      microvessels, the tracheas of anesthetized rats were surgically exposed and
      continuously suffused with Krebs Ringer bicarbonate warmed to 37 degrees C.
      Tracheal adventitial arterioles (13.0 to 41.0 microns initial diameter, n = 47)
      and venules (50.0 to 99.0 microns initial diameter, n = 46) were visualized with
      a videomicroscope, and vessel diameters were measured using videocalipers. When
      vessels were preconstricted with 10(-4) M phenylephrine, a selective alpha 1
      adrenergic agonist, and then treated with 10(-4) M furosemide, significant (p <
      0.05) dilation was observed in both arterioles (from 64.6 to 79.5% of their
      initial diameter) and venules (from 52.1 to 65.4% of their initial diameter).
      When vessels were preconstricted with 10(-4) phenylephrine, after pretreatment
      with the cyclooxygenase inhibitor indomethacin (5.0 mg/kg), 10(-4) M furosemide
      significantly dilated arterioles (from 77.5 to 93.0% of their initial diameter)
      and venules (from 58.5 to 80.1% of their initial diameter). In vessels
      preconstricted with 10(-3) M L-NAME, an inhibitor of nitric oxide synthesis,
      addition of 10(-4) M furosemide to the suffusion still caused significant
      dilation in arterioles, from 77.4 to 88.8% of their initial diameter, and in
      venules from 79.5 to 86.7% of their initial diameter. These data confirm that
      furosemide, when applied topically, dilates tracheal arterioles and venules by
      cyclooxygenase- and nitric oxide-independent mechanisms.

PMID- 9279228
TI  - Effects of inhaled nitric oxide on gas exchange in lungs with shunt or poorly
      ventilated areas.
AB  - Inhaled nitric oxide (NO) is a selective pulmonary vasodilator with beneficial
      effects on some lung diseases, yet conflicting results, particularly in chronic
      obstructive pulmonary disease, have been reported. We hypothesized that although
      inhaled NO would improve gas exchange in the presence of shunt (by increasing
      blood flow to normal areas), it could worsen gas exchange when areas of low
      ventilation-perfusion (VA/Q) ratio were present since these areas could be
      preferentially vasodilated by NO. We examined how approximately 80 ppm inhaled NO
      altered pulmonary gas exchange in anesthetized ventilated dogs with the
      following: (1) normal lungs (n = 8), (2) shunt (n = 9, 24.7% shunt) produced by
      complete obstruction of one lobar bronchus, and (3) VA/Q inequality (n = 8)
      created by partial obstruction of one lobar bronchus resulting in a bimodal VA/Q
      distribution with 13% perfusion of low VA/Q areas (0.005 < VA/Q < 0.1) without
      shunt. Inhaled No significantly reduced pulmonary arterial (p < 0.001) and wedge
      pressures (p < 0.01) and pulmonary vascular resistance (p < 0.01) without
      changing cardiac output in each group. In normal lungs, NO did not alter PaO2 or
      VA/Q inequality. However, with complete obstruction, shunt fell slightly (p <
      0.001) with NO. In lungs with VA/Q inequality, NO variably affected VA/Q
      matching, which was improved in some dogs and worsened in others. In these lungs,
      changes in pulmonary vascular resistance of the abnormal area of the lung were
      negatively correlated with changes in VA/Q dispersion (logSDQ) (R = -0.85, p <
      0.01) and positively correlated with PaO2 (R = 0.79, p < 0.05). We conclude that
      NO has net effects on pulmonary gas exchange, depending on the underlying lung
      pathology consistent with competing vasodilatory effects on the normal and
      abnormal areas that receive the gas.

PMID- 9279229
TI  - D-dimer testing for suspected pulmonary embolism in outpatients.
AB  - The plasma level of D-dimer, a fibrin degradation product (FDP), is nearly always
      increased in the presence of acute pulmonary embolism (PE). Hence, a normal D
      dimer level (below a cutoff value of 500 micrograms/L by enzyme-linked
      immunosorbent assay [ELISA]) may allow the exclusion of PE. To assess the
      negative predictive value of a D-dimer concentration below 500 micrograms/L in
      outpatients with suspected PE, and the safety of withholding anticoagulant
      treatment from such patients, we performed D-dimer assays, lower limb venous
      compression ultrasonography, and lung scans in 671 consecutive outpatients
      presenting in the Emergency Center of the Geneva University Hospital with
      suspected PE. Pulmonary angiography was reserved for patients with an
      inconclusive noninvasive workup. Patients with a normal D-dimer concentration
      were discharged without anticoagulant treatment and followed for 3 mo. The
      prevalence of PE was 29%, and D-dimer (using a cutoff of 500 micrograms/L) had a
      diagnostic sensitivity for PE of 99.5%. Overall diagnostic specificity of D-dimer
      was 41%, but it was lower among older patients. Of the 198 patients with a D
      dimer concentration below the cutoff value, 196 were free of PE, one had a PE,
      and one had incomplete information because of loss to follow-up. Thus, the
      negative predictive value of D-dimer concentration fell between 197 of 198 and
      196 of 198 cases of PE (99% [95% CI: 96.4 to 99.9]). Using a cutoff value of
      4,000 micrograms/L, the overall specificity of D-dimer concentration for PE was
      93.1%. In conclusion, a plasma D-dimer concentration below 500 micrograms/L
      allows the exclusion of PE in 29% of outpatients suspected of having PE.
      Withholding anticoagulation from such patients is associated with a conservative
      1% risk of thromboembolic events during follow-up.

PMID- 9279230
TI  - Differential inspiratory muscle pressure contributions to breathing during
      dynamic hyperinflation.
AB  - During dynamic hyperinflation, the ventilatory pump is facing increased demand
      because it must overcome the intrinsic positive end-expiratory pressure (PEEPi)
      and decreased capacity since it must operate at a dynamically increased end
      expiratory lung volume (EELV). The aim of this study was to evaluate the relative
      pressure contribution by the diaphragm and inspiratory rib cage muscles (RCMs)
      during dynamic hyperinflation. In six healthy subjects, dynamic hyperinflation
      was induced by limiting expiratory flow. The global inspiratory muscle pressure
      (delta Pmus,i) and transdiaphragmatic pressure (delta Pdi) were partitioned into
      the portion used to overcome PEEPi and the portion used to inflate the
      respiratory system. The delta Pdi/delta Pmus,i ratio was used to estimate the
      pressure contribution of RCMs relative to that of the diaphragm. Our results
      suggest that (1) with increasing severity of dynamic hyperinflation, there is a
      significant increase in the inspiratory pressure contribution of RCMs relative to
      that of the diaphragm for inflating the respiratory system; (2) during dynamic
      hyperinflation, especially at high EELV, the major pressure contribution of the
      diaphragm is to overcome the PEEPi-imposed inspiratory threshold load, whereas
      the inspiratory pressure needed for the subsequent task of inflating the
      respiratory system is largely contributed by RCMs. This arrangement is consistent
      with the change in mechanical advantages of RCMs and the diaphragm during the
      development of dynamic hyperinflation.

PMID- 9279231
TI  - Effect of chronic hyperinflation on diaphragm length and surface area.
AB  - We have used three-dimensional reconstructions obtained with spiral computed
      tomography to measure total diaphragm length (Ldl) and surface area (Adl), the
      length (Ldo) and surface area (Ado) of the dome, and the length (Lap) and surface
      area (Aap) of the zone of apposition in 10 hyperinflated patients with severe
      chronic obstructive pulmonary disease, or COPD (FEV1 = 27% predicted: FRC = 225%
      predicted) and 10 normal subjects matched for age, sex, and height. Measures of
      Ldl, Adl, Lap, and Aap decreased linearly between FRC and TLC in the two groups,
      but Ldo and Ado did not change. On average, patients' Adl and Aap at FRC were
      reduced to 73% and 54% of normal values, whereas Ado was unaffected. When
      compared at similar absolute lung volumes, mean diaphragm dimensions were similar
      in patients with COPD and normal subjects, but individual values were very
      variable in both groups. This variability was partly accounted for by differences
      in body weight: i.e., the greater the weight, the longer the diaphragm. We
      conclude that (1) patients with COPD have marked reductions in Adl and Aap at FRC
      but have diaphragm dimensions similar to those of normal subjects when compared
      at similar absolute lung volumes, and (2) normal subjects and patients with COPD
      show substantial intersubject variability in diaphragm dimensions that is partly
      explained by differences in body weight.

PMID- 9279232
TI  - Influence of neck muscles on mouth pressure response to cervical magnetic
      stimulation.
AB  - Measurement of mouth pressure (Pm) in response to electrical phrenic nerve
      stimulation (Es) provides a simple noninvasive means to assess diaphragm
      function. An even simpler measure would be to use the Pm twitch response (Pm,t)
      to cervical magnetic stimulation (CMS) rather than to Es. Because CMS coactivates
      the diaphragm and inspiratory neck muscles (INM), CMS-Pm,t accurately reflects
      diaphragm function only if the corresponding INM contraction does not produce
      inspiratory pressures by itself. In patients with recent-onset bilateral
      diaphragm paralysis, it has been demonstrated that CMS-Pm,t was indeed zero;
      however, INM hypertrophy could change this situation and lead CMS-Pm,t to
      overestimate the performance of the diaphragm. To address this issue, we studied
      nine patients with amyotrophic lateral sclerosis (ALS) who had evidence of
      diaphragmatic paralysis and compensatory hypertrophy and hyperactivity of
      inspiratory neck muscles. The response to CMS was described in terms of diaphragm
      electromyogram (EMG), Pm, and abdominal (AB) and rib cage (RC) motion. No EMG
      response to CMS could be observed in most cases, and CMS was always associated
      with AB paradox. Nevertheless, a negative Pm,t swing was recorded with an
      amplitude of -2.6 +/- 1.0 cm H2O (mean +/- SD). We conclude that inspiratory neck
      muscle hypertrophy can significantly influence the Pm response to CMS. This
      should be taken into account when using the CMS-Pm combination in patients with
      possible chronic diaphragm dysfunction.

PMID- 9279233
TI  - Neuromuscular activity and upper airway collapsibility. Mechanisms of action in
      the decerebrate cat.
AB  - We have shown that tracheal and tongue displacement represent two basic
      mechanisms by which upper airway collapsibility can be altered. In this study, we
      investigated whether hypercapnia, which activates upper airway muscles, alters
      upper airway collapsibility by a mechanism similar to tracheal or tongue
      displacement. To answer this question, we utilized a feline isolated upper airway
      preparation in which maximal inspiratory airflow (Vimax), the pharyngeal critical
      pressure (Pcrit) and the nasal resistance (Rn) upstream to the flow-limiting site
      (FLS) were measured. In protocol #1, upper airway airflow dynamics were studied
      at two levels of trachea displacement under either hypo- or hypercapnic
      conditions. We found that the increase in Vimax with 1 cm of caudal tracheal
      displacement was attenuated by hypercapnia (44 +/- 12 ml/s versus 81 +/- 7 ml/s
      during hypocapnia, p = 0.048), as was the decrease in Pcrit (-2.4 +/- 1.1 cm H2O
      versus -5.2 +/- 1.1 cm H2O, p = 0.001). In protocol #2, we investigated the
      effect of transecting the cervical strap muscles and hypoglossal nerves on
      airflow dynamics during hypercapnia. Vimax, Pcrit, and Rn did not change after
      transecting either the strap muscles or the hypoglossal nerves. We conclude that
      the primary mechanism for changes in Pcrit during hypercapnia is similar to
      trachea displacement and is mediated by muscles other than the straps or tongue.

PMID- 9279234
TI  - Pulmonary function in obese snorers with or without sleep apnea syndrome.
AB  - We evaluated pulmonary function abnormalities associated with the sleep apnea
      syndrome (SAS) in 170 habitual snorers without SAS (n = 62, apnea-hypopnea index
      [AHI] < 10 per hour of sleep), with moderately severe SAS (n = 56, 10 < or = AHI
      < 30) or with severe SAS (n = 52, AHI > or = 30). The three groups were similar
      regarding obesity (BMI approximately 30 kg.m-2) and smoking history
      (approximately 20 pack-years). Pulmonary function was assessed by spirometry,
      forced oscillation mechanics, and gas exchange studies. Forced expiratory flows
      decreased as the SAS severity increased (p < 0.001, p < 0.02, and p < 0.05 for
      FEF50, FEV1, and FEV1/VC, respectively). Multiple regression analysis showed that
      the correlation between FEV50 and the AHI persisted when smoking history was
      taken into account (p < 0.05), suggesting that SAS may be an independent risk
      factor for small airway disease. A highly significant correlation was found
      between specific respiratory conductance (sGrs) and the AHI (p < 0.0001). In a
      multiple regression analysis (p < 0.0001), variables that influenced sGrs were
      distal airway obstruction as assessed by FEV50 (p < 0.05), morphological upper
      airway abnormalities as assessed by cephalometric parameters (p < 0.02), and the
      AHI (p < 0.0005). SAS appears to be highly correlated to lower and upper airway
      obstruction, as demonstrated by a reduction in specific respiratory conductance,
      which adds to the increase in breathing load due to obesity.

PMID- 9279236
TI  - Validation of the St. George's Respiratory Questionnaire in bronchiectasis.
AB  - There is no disease-specific instrument available for health status assessment in
      bronchiectasis. We examined the stability, validity and responsiveness of a
      measure designed for asthma and COPD, the St. George's Respiratory Questionnaire
      (SGRQ), in this condition. One hundred and eleven patients were studied on 2
      separate d 6 mo apart. On both days each patient completed the SGRQ and measures
      of general and disease-specific health, mood, and fatigue. They also performed a
      shuttle walking test and comprehensive lung function tests. Repeatability was
      tested over 2 wk in 23 patients. The intraclass correlation (ri) for the SGRQ
      Total score was 0.97. The SGRQ component scores correlated well with relevant
      markers of disease activity. Examples include: SGRQ Symptoms score versus MRC
      Wheeze score, r = 0.634, p < 0.0001; Activity score versus shuttle walking test,
      r = -0.659, p < 0.0001; and impacts score versus physical fatigue, r = 0.610, p <
      0.0001. Changes in the SGRQ Total score from entry to follow-up also correlated
      with changes in other measures of the patients' health. There were significant
      differences in the SGRQ total score between patients who improved and those who
      deteriorated over the 6 mo in respect to wheeze (F = 5.6, p < 0.01) and
      breathlessness (F = 6.05, p < 0.01). We conclude that the SGRQ reflects impaired
      health in bronchiectasis patients.

PMID- 9279235
TI  - Interstitial lung disease in recent onset rheumatoid arthritis.
AB  - Interstitial lung disease (ILD) is associated with rheumatoid arthritis (RA);
      however, the prevalence and natural history are undefined. Our aim was to
      determine the prevalence of ILD associated with RA using a number of sensitive
      techniques in patients with joint disease of less than 2-yr duration. Patients
      who met ARA criteria for RA were recruited from community-based and hospital
      rheumatologists and assessed using the following measures: clinical, lung
      physiology, radiology (chest X-ray, high resolution CT [HRCT]), bronchoalveolar
      lavage (BAL) and 99mTc-DTPA nuclear scan. Thirty-six patients (25 female and 11
      male) of joint disease duration of (mean +/- SD) 13.2 +/- 8.6 mo were studied.
      Abnormalities consistent with ILD were found in one or more investigations in 21
      of 36 (58%), which were in lung physiology in 22%, CXR in 6%, HRCT in 33%, BAL in
      52%, and 99mTc-DTPA nuclear scan in 15%. Based on the results, they were
      categorized as having clinically significant ILD (Group 1), abnormalities
      compatible with ILD, but no clinically significant ILD (Group 2) and no
      abnormalities compatible with ILD (Group 3). Five of 36 (14%) were in Group 1, 16
      of 36 (44%) in Group 2, and 15 of 36 (42%) in Group 3. The only risk factor for
      the presence of abnormalities compatible with ILD was male gender (p < 0.04,
      Student's t test). In conclusion, changes consistent with ILD in early RA are
      frequent. The significance of these changes is being determined in a longitudinal
      study.

PMID- 9279237
TI  - Redefining end of test (EOT) criteria for pulmonary function testing in children.
AB  - In order for an individual FVC maneuver to be considered acceptable according to
      the 1994 American Thoracic Society (ATS) standards it must meet end of test (EOT)
      criteria of a minimum expiration time of 6 s with minimal volume change (0.03 L)
      over 1 s. We have found that while these criteria are often not met in children,
      most of the tests do meet the ATS criteria for reproducibility with repeated
      efforts. We, therefore, sought to develop new EOT criteria that would be more
      appropriate for children and in keeping with the findings for reproducibility.
      Using an exponential curve fitting of the volume time tracing, we determined a
      theoretical curve that closely approximated the actual curve (mean difference
      between actual and derived FEV1 0.01 +/- 0.04 L). The theoretical FVC (FVCFULL)
      at the point where the curve reached its asymptote was then determined using the
      fitted curve. Since this point could be difficult to reach for some patients, 95%
      of FVCFULL (FVC95) was proposed as the new EOT in children. Data from 382
      patients were reviewed. Their ages ranged from 5 to 18 yr and their FEV1s from 21
      to 120% of predicted. Only 19% of the patients met current ATS EOT requirements
      despite the fact that 91% met the reproducibility criteria for both FEV1 and FVC.
      However, 90% of them reached their FVC95. When this was broken down by age, 37%
      of those < or = 7 yr failed to reach FVC95 whereas only 4% of the older children
      failed to do so. It is proposed that patients be coached to obtain maximal effort
      and that the curves be individually fitted to an exponential equation to
      determine whether the patient has achieved EOT as defined by FVC95.

PMID- 9279238
TI  - Air pollution and respiratory health among children with asthmatic or cough
      symptoms.
AB  - During the winter of 1994, the association between daily changes in air pollution
      and in the respiratory health of children 7 to 12 yr of age were studied in
      Kuopio, Finland. Seventy-four children with asthmatic symptoms and 95 children
      with cough only, living either in urban or suburban areas, were followed for 3
      mo. During the study period, the mean daily concentration of particulate air
      pollution (PM10) was 18 micrograms/m3 in the urban area and 13 micrograms/m3 in
      the suburban area. Lagged concentrations of PM10, black smoke, and NO2 were
      significantly associated with declines in morning peak expiratory flow (PEF)
      among asthmatic children. The regression coefficient (x10) for a 2-d lag of PM10
      was -0.911 (SE, 0.386) in the urban and -1.05 (0.596), in the suburban area.
      Among children with cough only, PM10, black smoke, and NO2 were not significantly
      associated with PEF. In the urban area, there was a significant association
      between SO2 and morning and evening PEF and incidence of upper respiratory
      symptoms among children who cough only. No other associations between air
      pollution and evening PEF or respiratory symptoms were observed. This study
      suggests that particulate air pollution is associated with respiratory health,
      especially among children with asthmatic symptoms.

PMID- 9279239
TI  - Effect of surgical lung volume reduction on breathing patterns in severe
      pulmonary emphysema.
AB  - Surgical lung volume reduction may improve pulmonary function and dyspnea in
      advanced pulmonary emphysema. To investigate mechanisms of these beneficial
      effects we studied breathing patterns before and after surgery. Nineteen patients
      with diffuse pulmonary emphysema (FEV1 < 35% of predicted, total lung capacity >
      130% predicted) were studied within 1 mo before, and 1.5 to 7 mo after
      thoracoscopic volume reduction. Changes of rib cage and abdominal volumes were
      monitored with calibrated respiratory inductive plethysmography for 20 to 60 min
      during natural breathing at rest. Pulmonary function and dyspnea were also
      assessed. Postoperative tidal volumes, respiratory cycle times, and minute
      ventilation were not significantly different from preoperative values. The
      contribution of abdominal volume changes to tidal volumes increased from a mean
      +/- SD of 43 +/- 17% preoperatively to 58 +/- 14% postoperatively (p = 0.03). The
      fraction of inspiratory time with abdominal paradoxical motion decreased from
      12.3 +/- 8.3% preoperatively to 5.1 +/- 5.1% postoperatively (p = 0.02). The
      phase shift between rib cage and abdominal motion was reduced postoperatively.
      Hyperinflation, airway obstruction, and subjective ratings of dyspnea were
      significantly improved. The better synchronization of rib cage-abdominal motion
      and the greater contribution of abdominal volume changes to tidal volumes are
      consistent with a reduction of inspiratory loading and a greater force-generating
      capacity of the diaphragm after surgery.

PMID- 9279240
TI  - Lung volume reduction surgery improves maximal O2 consumption, maximal minute
      ventilation, O2 pulse, and dead space-to-tidal volume ratio during leg cycle
      ergometry.
AB  - Early experience suggests that lung volume reduction surgery improves exercise
      tolerance as measured by the 6-min walk distance in patients with emphysema. To
      identify the physiologic mechanism(s) by which lung volume reduction surgery
      improved exercise, we performed progressive cardiopulmonary exercise testing,
      including rest and peak exercise blood gas determinations, on 21 consecutive
      patients before and 3 mo after lung volume reduction surgery. Maximal work
      (median, range, % change) increased 17.5 watts (-13 to +44 watts, 46%, p < 0.05),
      maximal oxygen consumption increased 0.16 L/min (-0.17 to +0.48, 25%, p < 0.05),
      maximal ventilation increased 6.6 L/min (-7 to +26 L/min, 27%, p < 0.05), and the
      dead space/tidal volume ratio at peak exercise decreased 0.07 (-0.22 to +0.09,
      12%, p < 0.05), exclusively as a result of an increase in the tidal volume. After
      lung volume reduction surgery heart rate decreased at the point of isowatt
      exercise, from 115 to 111 beats/min (p < 0.05). No difference was observed in the
      other physiologic variables measured at isowatt exercise. In 13 patients
      exercised while breathing room air, the alveolar-to-arterial O2 difference
      increased, and the arterial O2 tension decreased from rest to peak exercise both
      before and after the operation, but significant changes in this response were not
      observed after surgery. The primary problem limiting exercise performance in
      these patients was the limited ventilatory capacity as 16 and 13 of the 21
      subjects developed acute respiratory acidemia at peak exercise before and after
      surgery, respectively. Lung volume reduction surgery in patients with severe
      emphysema improved maximal ventilation, thereby improving maximal exercise
      performance.

PMID- 9279241
TI  - Effects of early surfactant treatment persisting for one week after lung
      transplantation in rats.
AB  - We investigated whether pulmonary surfactant in rat lung transplants recovered
      during the first week post-transplantation, along with symptoms of the
      reimplantation response, and whether this recovery was affected by early
      surfactant treatment. The severity of pulmonary injury was varied by
      transplanting left lungs with 6-h and 20-h ischemia (n = 12 and 19,
      respectively). Half of the transplants were treated by instillation of surfactant
      before reperfusion. Lungs from sham operated, and normal rats (n = 4 and 5,
      respectively) served as controls. The pulmonary injury severely impaired lung
      transplant function; 10 of the worst affected animals died. After 1 wk, symptoms
      of reimplantation response and properties of pulmonary surfactant were assessed.
      If untreated, the reimplantation response had almost resolved in the 6-h but not
      in the 20-h ischemia group; pulmonary surfactant, however, continued to be
      deficient in both ischemia groups (low amounts of surfactant phospholipids and
      surfactant protein A [SP-A]). Surfactant treatment improved the recovery from
      injury in the 20-h ischemia group resulting in normal lung function and amounts
      of surfactant phospholipids. Amounts of SP-A were not improved by surfactant
      treatment. In conclusion, early surfactant treatment enhances recovery from
      transplantation injury and is persistently beneficial for pulmonary surfactant in
      lung transplants.

PMID- 9279242
TI  - Tuberculosis prevention among foreign-born persons in Seattle--King County,
      Washington.
AB  - The purpose of this study was to evaluate the outcomes of classified immigrant
      and refugee (I&R) screening and of contact investigation (CI) of foreign-born TB
      cases in Seattle--King County (SKC), Washington. We reviewed I&R evaluations from
      the SKC TB clinic for 1992-1994 and contact evaluation records for 54 randomly
      selected U.S.-born and foreign-born pulmonary TB patients from 1993. Among 942
      I&R evaluated, 693 (74%) had positive tuberculin skin tests (TST). Preventive
      therapy (PT) was prescribed for 324 (34%) and treatment for 49 (5%). The
      remaining 377 were dismissed, of whom 96% did not meet American Thoracic Society
      PT criteria. Contacts of foreign-born cases were more numerous (6.0 versus 3.4
      per case, p = 0.04), and significantly more likely to be TST-positive (50% versus
      18%) and to be started on PT (40% versus 23%). The large number of I&R eligible
      for treatment or PT emphasizes the benefit of prompt evaluation of new arrivals.
      CI provides an excellent opportunity to screen foreign-born persons at high risk
      for active TB.

PMID- 9279243
TI  - Pneumonia with serological evidence of acute infection with the Chlamydia-like
      microorganism "Z".
AB  - "Z" is a recently discovered microorganism that may belong to a new genus in the
      family Chlamydiaceae. Using an ELISA test we developed, we measured levels of
      serum antibody against "Z" for 308 paired sera obtained from adult patients
      hospitalized with community-acquired pneumonia (CAP). In 114 patients (37%),
      serological evidence of past infection with "Z" was found. In eight patients
      (2.6%) there was serological evidence of acute infection with this pathogen. In
      four of these eight patients, no other pathogen for CAP was identified despite an
      intensive serological investigation encompassing 13 etiological agents. The four
      patients were about 30 yr old, and three of them had no history of chronic
      illness. Their illness was characterized by high fever, a nonproductive cough,
      gastrointestinal symptoms, a shift to the left in the white blood cell count, and
      a prompt, dramatic response to erythromycin therapy. We conclude that the
      microorganism "Z", or a close variant, is infectious for humans, in some cases
      causing CAP. In these cases the disease is mild and responds quickly to treatment
      with erythromycin.

PMID- 9279244
TI  - Significance of the isolation of Candida species from respiratory samples in
      critically ill, non-neutropenic patients. An immediate postmortem histologic
      study.
AB  - The diagnosis of pulmonary candidiasis is still controversial. We undertook a
      prospective study on 25 non-neutropenic, mechanically ventilated (> 72 h)
      patients who died in our ICU with the aim of assessing the incidence and
      significance of the isolation of Candida species from quantitative cultures of
      immediate postmortem lung biopsies and different respiratory sampling techniques.
      Immediate postmortem respiratory samples (endotracheal aspirate, protected
      specimen brush [PSB], bronchoalveolar lavage [BAL], blind biopsies [average
      14/patient], and bilateral bronchoscopically guided biopsies [two per patient])
      were taken from all patients. Lung tissue specimens were histologically examined.
      Respiratory samples were classified as having Candida or otherwise. Ten (40%)
      patients had at least one pulmonary biopsy yielding Candida spp. Among these 10
      patients with Candida isolates, only two had definite pulmonary candidiasis. A
      total of 470 microorganisms were isolated from 280 of 375 (77%) lung biopsy
      samples in all 25 patients. Candida species represented 9% (n = 40) of the
      isolates, corresponding to 10 patients (40%). In the 10 patients in whom Candida
      species was isolated from pulmonary biopsies, this was always associated with the
      isolation of the same microorganism from one of the sampling methods.
      Quantitative cultures of Candida species from different sampling methods
      correlated well among each other but could not discriminate the presence from
      absence of Candida pneumonia. A logistic regression model adjusted for the
      presence of antibiotics, days of antibiotic treatment, mechanical ventilation
      period, age, ARDS, parenteral nutrition, and gender did not show any independent
      risk factor for developing positive pulmonary samples for Candida species. The
      incidence of Candida isolation from pulmonary biopsies in critically ill
      mechanically ventilated, non-neutropenic patients who die is high (40%). However,
      the incidence of definite Candida pneumonia was 8%. We also found that Candida
      colonization is uniform throughout the different lung regions, and that the
      presence of Candida in respiratory samples, independently of quantitative
      cultures, is not a good marker of Candida pneumonia in critically ill, non
      neutropenic, non-AIDS patients.

PMID- 9279245
TI  - Transforming growth factor-beta expression in mucosal biopsies in asthma and
      chronic bronchitis.
AB  - We assessed whether transforming growth factor-beta (TGF-beta), a fibrogenic
      growth factor, may be involved in remodeling of asthma and chronic bronchitis;
      its expression was compared with that of epidermal growth factor (EGF) and
      granulocyte macrophage colony-stimulating factor (GM-CSF) in bronchial mucosal
      biopsies from 13 normal subjects, 24 asthmatics, and 19 patients with chronic
      bronchitis. TGF-beta immunoreactivity was highly increased in epithelium and
      submucosa of those with bronchitis and to a lesser extent in asthmatics. By
      comparison, with normal subjects, EGF immunoreactivity was significantly
      increased in the epithelium of bronchitic subjects and submucosa of asthmatics,
      and, GM-CSF immunoreactivity was increased in both epithelial and submucosal
      cells of asthmatics and to a lesser extent in submucosa of bronchitics. A
      significant correlation was found between the number of epithelial or submucosal
      cells expressing TGF-beta in both asthma and chronic bronchitis and basement
      membrane thickness and fibroblast number. No such correlation was found for EGF
      or GM-CSF. in situ hybridization for TGF-beta 1 mRNA confirmed the results
      obtained by immunohistochemistry. By combining in situ hybridization and
      immunohistochemistry, it was found that eosinophils and fibroblasts were
      synthetizing TGF-beta in asthma and bronchitis. These data suggest that TGF-beta,
      but not EGF or GM-CSF, is involved in airways remodeling in asthma and chronic
      bronchitis.

PMID- 9279246
TI  - Increased endothelin-1 in bleomycin-induced pulmonary fibrosis and the effect of
      an endothelin receptor antagonist.
AB  - Idiopathic pulmonary fibrosis (IPF) is characterized by an alveolitis with
      epithelial and endothelial damage progressing to fibrosis. Numerous mediators
      have been implicated in this complex process. Studies in humans have shown that
      endothelin-1 (ET-1), a vasoconstrictor and mitogenic peptide, is a mediator in
      IPF. To determine the role of ET-1 and endothelin-converting enzyme (ECE)-1 and
      the effect of Bosentan, an ET receptor antagonist, in an animal model of IPF, we
      studied three groups of rats (n = 6 each): Group 1, control, received saline;
      Group 2, fibrosis, received 1.5 U bleomycin intratracheally; Group 3, fibrosis
      Bosentan treated, received bleomycin and Bosentan daily by gavage. After 28 d,
      right upper lobes were fixed for immunohistochemistry (IHC) and sections were
      stained with antisera to ET-1 and ECE-1 and graded semiquantitatively. Sections
      from left lungs were embedded in paraffin and stained for light microscopic
      morphometry to quantitate the fibrosis. By IHC, we found increased ET-1
      immunoreactivity (ir) in airway epithelium and inflammatory cells, and ECE-1-ir
      in airway epithelium, type II pneumocytes and endothelial cells (p < 0.05). By
      morphometry, the volume fraction (Vv) of connective tissue (CT) increased and the
      Vv of air decreased in the fibrosis group compared with that in the control
      group. Bosentan reduced the Vv of CT and increased the Vv of air compared with
      that in the fibrosis group (p < 0.05). These results indicate that ET-1 is
      involved in the pathogenesis of pulmonary fibrosis in the rodent model and that
      blockage of its receptors reduces the fibrosis.

PMID- 9279247
TI  - Experimental rhinovirus 16 infection. Effects on cell differentials and soluble
      markers in sputum in asthmatic subjects.
AB  - Asthma exacerbations are often associated with respiratory virus infections,
      particularly with rhinovirus. In the present study we investigated the effect of
      experimental rhinovirus 16 (RV16) infection on airway inflammation as assessed by
      analysis of hypertonic saline-induced sputum. Twenty-seven nonsmoking atopic,
      mildly asthmatic subjects participated in a placebo-controlled parallel study.
      RV16 (n = 19) or its diluent (n = 8) was nasally administered. Sputum inductions
      were performed at entry and on Days 2 and 9 after inoculation, and airway
      responsiveness to histamine (PC20) was measured on Days 4 and 11. Cell
      differentials and levels of albumin, eosinophil cationic protein (ECP), IL-8, and
      IL-6 were determined. The cellular origin of IL-8 was investigated by
      intracellular staining. RV infection was confirmed by culture and/or by antibody
      titer rise in each of the RV16-treated subjects. There were no significant
      changes in the sputum differentials of nonsquamous cells (MANOVA, p > or = 0.40).
      In the RV16 group, there was a significant increase in the levels of ECP, IL-8,
      and IL-6 at Day 2 after infection (p < 0.05), whereas the albumin levels did not
      change (p = 0.82). The levels of IL-8 and IL-6 remained elevated for as long as 9
      d after infection (p < 0.05). The increase in the percentage of IL-8 positive
      cells at Day 2 after infection could be attributed to the increase in IL-8
      positive neutrophils (p < 0.02). There was a significant decrease in PC20 at Day
      4 (p = 0.02), which was no longer significant at Day 11 (p = 0.19). The decrease
      in PC20 correlated significantly with the increase in ECP in the first week (r = 
      0.60) and with the change in the percentage eosinophils in the second week after
      inoculation (r = -0.58). We conclude that experimental RV16 infection in atopic
      asthmatic subjects increases airway hyperresponsiveness in conjunction with
      augmented airway inflammation, as reflected by an increase in ECP, IL-8, and IL-6
      in sputum. Our results suggest that the RV16-enhanced airway hyperresponsiveness
      is associated with eosinophilic inflammation.

PMID- 9279248
TI  - Alterations of the endogenous surfactant system in septic adult rats.
AB  - Sepsis is the most common factor leading to the acute respiratory distress
      syndrome (ARDS) and is associated with the highest mortality rate. It has been
      suggested that the pulmonary surfactant system is altered and contributes to the
      lung dysfunction associated with ARDS. The objective of this study was to
      characterize the lung injury, specifically the endogenous surfactant system in
      septic adult rats. Sepsis was induced in male Sprague-Dawley rats by cecal
      ligation and perforation and resulted in significant increases in heart rates,
      respiratory rates, and lactate levels along with positive blood cultures in
      septic animals compared with a sham control group. Two distinct septic groups
      were developed, a septic group and a sepsis with lung injury (septic+LI) group.
      The septic group had no significant differences in oxygenation compared with the
      sham group, whereas the septic+LI group had significantly lower PaO2 and higher A
      a gradient values compared to both the sham and septic groups. The total
      surfactant pool size was significantly lower in the septic+LI group compared with
      the sham group. The small surfactant aggregate to large surfactant aggregate
      ratio was significantly lower in the septic group and was further reduced in the
      septic+LI group. There were also significantly higher levels of surfactant
      protein A (SP-A) in both septic and septic+LI groups compared to the sham group.
      These results demonstrated that the endogenous surfactant system was altered in
      systemic sepsis without lung dysfunction and is further altered when a lung
      injury is present.

PMID- 9279249
TI  - Prenatal glucocorticoid and T4 effects on lung morphology in preterm lambs.
AB  - Prenatal glucocorticoid plus T4 treatment of fetal sheep results in improvements
      in oxygenation, gas exchange, lung mechanics, and lung volumes after preterm
      delivery. We have evaluated the morphometric changes in the lungs of lambs
      exposed to betamethasone and T4 48 h before preterm delivery at 121 and 135 d
      gestation and related those changes to the physiologic improvements in lung
      function. The lungs used for the morphometric studies were from lambs with
      postnatal physiologic responses similar to those of the entire group of lambs
      reported previously (16). At both 121 and 135 d gestation, lung gas volumes and
      fixed tissue volumes increased, the percent of collapsed (nonaerated) parenchyma
      decreased, and the percent of perilobular connective tissue decreased with both
      gestational age and prenatal hormone exposure. Alveolar size, as estimated by
      mean linear intercept length, did not change with gestation or hormone exposure,
      but there was a decrease in alveolar wall thickness with advancing gestation and
      at each gestation with hormone exposure. The major anatomic effect of prenatal
      hormone exposure was a decrease in alveolar wall thickness and an increase in
      aerated parenchyma, effects that were consistent with the physiologic
      improvements in postnatal lung function.

PMID- 9279250
TI  - Tissue factor expression and fibrin deposition in the lungs of patients with
      idiopathic pulmonary fibrosis and systemic sclerosis.
AB  - Although abnormalities of alveolar fibrin turnover have been reported to play a
      role in the development of idiopathic pulmonary fibrosis (IPF), the
      pathophysiological relevance remains unclear. We therefore investigated the
      localization of tissue factor (TF) and fibrin deposition in patients with IPF
      using immunohistochemistry and compared the results with those from patients who
      had interstitial pneumonia associated with systemic sclerosis (IP-SSc) and
      idiopathic bronchiolitis obliterans with organizing pneumonia (BOOP). Expression
      of TF-mRNA was also assessed, using in situ hybridization with a digoxigenin
      labeled cRNA probe. In patients with IPF, IP-SSc, and idiopathic BOOP, the TF
      antigen was positively stained in type II pneumocytes and in some alveolar
      macrophages. The fibrin antigen was stained in the type II pneumocytes and the
      adjacent area. Tissue factor-mRNA was expressed in the type II pneumocytes and in
      some alveolar macrophages. Neither TF antigens nor TF-mRNA were detected in the
      normal lung. These results indicate that type II pneumocytes are a major source
      of TF, suggesting that TF production in these cells is closely related to fibrin
      deposition in the lungs of people with these diseases.

PMID- 9279251
TI  - CD4-positive T-lymphocytes infiltrate the bronchial mucosa of patients with
      Sjogren's syndrome.
AB  - To investigate the degree and the type of inflammation in the bronchial mucosa in
      patients with Sjogren's syndrome, we examined lobar bronchial biopsies obtained
      from 10 patients with Sjogren's syndrome (six with primary and four with
      secondary) and eight control subjects. Histochemistry with hematoxylin-eosin was
      performed both to identify the number of mononuclear cells and eosinophils and to
      measure the thickness of the basement membrane. Immunohistochemistry was
      performed to identify neutrophils (neutrophil-elastase), macrophages (CD68), and
      T-lymphocyte subpopulations (CD4 and CD8) in the submucosa. Subjects with
      Sjogren's syndrome presented a greater number of CD4-positive T-lymphocytes than
      did the normal control subjects (p = 0.0129). Instead, eosinophils, neutrophils,
      macrophages, CD8 positive T-lymphocytes, and basement membrane thickness were
      similar in the two groups. There were no differences in cell counts between
      patients with primary and those with secondary Sjogren's syndrome and between
      symptomatic and asymptomatic patients. No correlation was found between cell
      counts, symptoms, lung volumes, and disease duration. This study has shown that
      patients with Sjogren's syndrome have an increased number of CD4 positive T
      lymphocytes in the bronchial mucosa outside of the bronchial glands, supporting
      the concept that, in the airways. Sjogren's syndrome involves also extraglandular
      tissues.

PMID- 9279252
TI  - Transforming growth factor-beta 1 in asthma. Measurement in bronchoalveolar
      lavage fluid.
AB  - Airway wall remodeling is an established pathological feature in asthma. Its
      causes are not well understood, but one mediator of potential relevance is
      transforming growth factor-beta 1 (TGF-beta 1). We have measured levels of
      immunoreactive TGF-beta 1 in bronchoalveolar lavage (BAL) fluid from clinically
      stable atopic asthmatics and healthy control subjects. We have also examined the
      influence of allergen exposure on TGF-beta 1 release in the airways using a
      segmental bronchoprovocation model, with BAL performed at two time points
      following endobronchial allergen and sham saline challenges. Basal concentrations
      of TGF-beta 1 were significantly higher in asthmatics than control subjects
      (median 8.0 versus 5.5 pg/ml, p = 0.027). Following segmental bronchoprovocation,
      concentrations of TGF-beta 1 at the allergen- and saline-challenged sites were
      not significantly different after 10 min, (31.3 versus 25.0 pg/ml, p = 0.78), but
      after 24 h there were significantly higher TGF-beta 1 concentrations at the
      allergen-challenged sites (46.0 versus 21.5 pg/ml, p = 0.017). We conclude that
      basal TGF-beta 1 levels in the airways are elevated in atopic asthma and that
      these levels increase further in response to allergen exposure. These findings
      are consistent with the hypothesis that TGF-beta 1 is implicated in airway wall
      remodeling in asthma.

PMID- 9279253
TI  - Increase in pulmonary ventilation-perfusion inequality with age in healthy
      individuals.
AB  - Arterial oxygen tension (PaO2) is known to decrease with age, and this is
      accompanied by a number of changes in mechanical properties of the lungs,
      including loss of elastic recoil and increase in closing volume. The changes in
      respiratory mechanics with age could induce greater ventilation/perfusion (VA/Q)
      mismatch and thus explain the decrease in PaO2. In 64 normal subjects aged 18 to
      71 yr (lifetime nonsmokers with normal spirometry), we measured VA/Q inequality
      and arterial respiratory blood gases (PaO2 and PaCO2) at rest in the seated
      position. VA/Q mismatch, represented by the second moments of the blood flow and
      ventilation distributions (log SDQ and log SDV) increased with age, but only
      slightly (mean log SDQ was 0.36 at age 20 yr and 0.47 at age 70 yr). PaO2 fell by
      a correspondingly small amount of 6 mm Hg. Previously established upper 95%
      confidence limits for log SDQ (0.60) and log SDV (0.65) in subjects at age 20 yr
      were confirmed. At age 70 yr, the upper limits of reference for log SDQ are 0.70
      and for log SDV 0.75. The study shows that an increased alveolar-arterial O2
      gradient with age is due to VA/Q inequality rather than to shunting.

PMID- 9279255
TI  - Effect of upper respiratory tract infection in patients with neuromuscular
      disease.
AB  - Respiratory muscle strength during acute upper respiratory tract infection (URI)
      was assessed in patients with various forms of neuromuscular disease. Vital
      capacity (VC), oxygen saturation, end-tidal PCO2, maximal inspiratory pressure
      (MIP), and maximal expiratory pressure (MEP) were determined in 25 stable
      patients with various forms of neuromuscular disease. Thirteen episodes of URI
      developed in 10 patients. Respiratory parameters were reassessed within 24-36 h
      following the onset of symptoms in each patient. In patients with URI, mean
      baseline VC, MIP, and MEP were 1.16 L +/- 0.14, 49.2 cm H2O +/- 6.8, and 35.5 cm
      H2O +/- 3.8 and fell to 1.01 L +/- 0.15, 37.1 cm H2O +/- 6.2, and 25.5 cm H2O +/-
      3.0 during URI (p < 0.05 for each), respectively. Mean baseline PCO2 and oxygen
      saturation were 39.1 mm Hg +/- 1.1 and 95.1% +/- 1.0, and during URI, 43.9 mm Hg
      +/- 2.1 (p < 0.05) and 95.0% +/- 1.0 (NS), respectively. Five episodes of
      significant hypercapnia were observed in 4 patients. All parameters returned to
      near baseline values following recovery. We conclude that patients with various
      forms of neuromuscular disease develop reductions in respiratory muscle strength
      in association with URI. Unlike normal subjects, however, these decrements in
      respiratory muscle function may result in symptoms of shortness of breath,
      reductions in vital capacity, and acute hypercapnia in this patient population.

PMID- 9279254
TI  - In vivo treatment with endotoxin increases rat pulmonary vascular contractility
      despite NOS induction.
AB  - Pulmonary hypertension is a feature of clinical and experimental acute lung
      injury. Nitric oxide (NO) synthesis is increased in hyporesponsive systemic and
      pulmonary conductance arteries after endotoxin (LPS) injection in the rat. We
      examined the effects of NO synthase (NOS) induction by LPS on vascular reactivity
      of the isolated perfused rat lung (IPL) using the selective inducible (iNOS)
      inhibitor aminoguanidine (AG). Baseline pulmonary artery pressures (Ppa) were
      higher in the LPS compared with the sham-treated rats and were further increased
      only in the LPS-treated group by AG. Increased NOS activity in whole lung and the
      vasopressor effect of AG suggested that iNOS was active in pulmonary resistance
      vessels after LPS treatment. Vasoconstriction to hypoxia, angiotensin II (AII),
      and prostaglandin F2 alpha (PGF2 alpha) was enhanced or unchanged in LPS-treated
      rats despite NOS induction. Hence, iNOS activity counterbalances increased
      pulmonary vascular contractility in this model.

PMID- 9279256
TI  - Bronchiolitis obliterans and IgA nephropathy. A new cause of pulmonary-renal
      syndrome.
AB  - IgA nephropathy is a common form of glomerulonephritis, classically manifested by
      asymptomatic hematuria. Although the exact pathophysiologic mechanism is still
      unknown, renal damage has been related to mesangial deposition of IgA-containing
      immune complexes. In recent years, some lung diseases have been associated with
      IgA nephropathy, including pulmonary hemorrhage and sarcoidosis. We report a
      patient with idiopathic bronchiolitis obliterans who developed a rapidly
      progressive glomerulonephritis due to IgA deposits. Extensive deposits of IgA
      were also found in the lungs, thus suggesting a pathogenetic role for IgA in
      tissue injury at both organ levels. To our knowledge this association has not
      been previously described in the literature.

PMID- 9279257
TI  - Passive mechanics of lung and chest wall in patients who failed or succeeded in
      trials of weaning.

PMID- 9279258
TI  - Lymphangioleiomyomatosis: new insights.

PMID- 9279259
TI  - Genetic screening and public health.

PMID- 9279260
TI  - Adolescent HIV testing--who says who signs?

PMID- 9279261
TI  - The accurate measurement of gestational age--a critical step toward improving
      fetal death reporting and perinatal health.

PMID- 9279262
TI  - Public participation in medical policy-making and the status of consumer
      autonomy: the example of newborn-screening programs in the United States.
AB  - OBJECTIVES: State newborn-screening programs collectively administer the largest
      genetic-testing initiative in the United States. We sought to assess public
      involvement in formulating and implementing medical policy in this important area
      of genetic medicine. METHODS: We surveyed all state newborn-screening programs to
      ascertain the screening tests performed, the mechanisms and extent of public
      participation, parental access to information, and policies addressing parental
      consent or refusal of newborn screening. We also reviewed the laws and
      regulations of each state pertaining to newborn screening. RESULTS: Only 26 of
      the 51 state newborn-screening programs reported having advisory committees that
      include consumer representation. Fifteen states reported having used
      institutional review boards, another venue for public input. The rights and roles
      of parents vary markedly among newborn-screening programs in terms of the type
      and availability of screening information as well as consent-refusal and follow
      up policies. CONCLUSIONS: There is clear potential for greater public
      participation in newborn-screening policy-making. Greater public participation
      would result in more representative policy-making and could enhance the quality
      of services provided by newborn-screening programs.

PMID- 9279263
TI  - Sociometric risk networks and risk for HIV infection.
AB  - OBJECTIVES: This study examined whether networks of drug-injecting and sexual
      relationships among drug injectors are associated with individual human
      immunodeficiency virus (HIV) serostatus and with behavioral likelihood of future
      infection. METHODS: A cross-sectional survey of 767 drug injectors in New York
      City was performed with chain-referral and linking procedures to measure large
      scale (sociometric) risk networks. Graph-theoretic algebraic techniques were used
      to detect 92 connected components (drug injectors linked to each other directly
      or through others) and a 105-member 2-core within a large connected component of
      230 members. RESULTS: Drug injectors in the 2-core of the large component were
      more likely than others to be infected with HIV. Seronegative 2-core members
      engaged in a wide range of high-risk behaviors, including engaging in risk
      behaviors with infected drug injectors. CONCLUSIONS: Sociometric risk networks
      seem to be pathways along which HIV travels in drug-injecting peer groups. The
      cores of large components can be centers of high-risk behaviors and can become
      pockets of HIV infection. Preventing HIV from reaching the cores of large
      components may be crucial in preventing widespread HIV epidemics.

PMID- 9279264
TI  - Job strain and blood pressure in African Americans: the Pitt County Study.
AB  - OBJECTIVES: This report examined whether job strain (or its components, decision
      latitude and job demands) was associated with elevated blood pressure levels in a
      community-based sample of 726 African-American adults. METHODS: Blood-pressure,
      anthropometric, behavioral, demographic, and psychosocial data were collected for
      the current cross-sectional analyses during home interviews conducted for the
      second wave (1993) of the Pitt County Study (North Carolina), a prospective
      cohort study of hypertension among African Americans. RESULTS: Job strain was not
      associated with blood pressure among men or women in this study. However, men in
      the 80th percentile of decision latitude had more than a 50% decrease in the
      prevalence of hypertension compared with men in the 20th percentile (odds ratio =
      .46, 95% confidence interval = .22, .96). CONCLUSIONS: These results indicate
      that decision latitude may be important for hypertension risk among African
      American men. More research is needed on African Americans to determine why job
      strain and its two component variables differ in their associations with blood
      pressure for men and women.

PMID- 9279266
TI  - Youth and violence on local television news in California.
AB  - OBJECTIVES: This study explores how local television news structures the public
      and policy debate on youth violence. METHODS: A content analysis was performed on
      214 hours of local television news from California. Each of the 1791 stories
      concerning youth, violence, or both was coded and analyzed for whether it
      included a public health perspective. RESULTS: There were five key findings.
      First, violence dominated local television news coverage. Second, the specifics
      of particular crimes dominated coverage of violence. Third, over half of the
      stories on youth involved violence, while more than two thirds of the violence
      stories concerned youth. Fourth, episodic coverage of violence was more than five
      times more frequent than thematic coverage, which included links to broader
      social factors. Finally, only one story had an explicit public health frame.
      CONCLUSIONS: Local television news provides extremely limited coverage of
      contributing etiological factors in stories on violence. If our nation's most
      popular source of news continues to report on violence primarily through crime
      stories isolated from their social context, the chance for widespread support for
      public health solutions to violence will be diminished.

PMID- 9279265
TI  - Psychiatric symptoms in adolescence as predictors of obesity in early adulthood:
      a longitudinal study.
AB  - OBJECTIVES: This study examined the longitudinal relationship between
      psychopathology and obesity in young adulthood. METHODS: More than 700 youth in a
      population-based sample were psychiatrically assessed in 1983 (mean age = 14
      years) and 1992 (mean age = 22 years). Self-reported body mass index (BMI) in
      1992 was regressed on measures of depression and conduct disorder as well as a
      set of covariates including indices of physical health, social class,
      intelligence, and cigarette and alcohol use. Associations were examined with BMI
      treated as a continuous variable and with a binary index of obesity derived from
      the BMI distribution in each gender. RESULTS: BMI in young adults was positively
      related to a number of covariates. With all covariates controlled, BMI was
      inversely related to adult depressive symptoms in males but not females. BMI was
      positively related to adolescent symptoms of conduct disorder in both sexes.
      Similar associations were found between psychiatric symptoms and obesity.
      CONCLUSIONS: Conduct disorder symptoms in adolescence predicted BMI and obesity
      in early adulthood. These associations remained after controlling for factors
      that can affect the association between psychopathology and obesity.

PMID- 9279267
TI  - National trends in the mortality of children with sickle cell disease, 1968
      through 1992.
AB  - OBJECTIVES: This paper describes national trends in mortality of children with
      sickle cell disease and the settings in which death occurred. METHODS: United
      States death certificate data from 1968 through 1992 were used to calculate
      mortality rates of Black children with sickle cell disease 1 to 14 years old.
      Deaths from trauma, congenital anomalies, and perinatal conditions were excluded.
      RESULTS: Between 1968 and 1992, mortality rates of Black children with sickle
      cell disease decreased 41% for 1- to 4-year-olds, 47% for 5- to 9-year-olds, and
      53% for 10- to 14-year-olds. During 1986 through 1992, children who died before
      hospital admission accounted for 41% of deaths among 1- to 4-year-olds, 27% among
      5- to 9-year-olds, and 12% among 10- to 14-year-olds. CONCLUSIONS: Survival of
      Black children with sickle cell disease has improved markedly since 1968. A
      substantial proportion of deaths continue to occur prior to hospital admission.
      Trends in sickle cell mortality can be monitored inexpensively with death
      certificate data.

PMID- 9279268
TI  - Quality assessment of fetal death records in Georgia: a method for improvement.
AB  - OBJECTIVES: Although more fetal deaths than neonatal deaths occur, routinely
      collected fetal death data are seldom used for perinatal epidemiologic research
      because of data quality concerns. We developed a strategy for identifying and
      correcting errors in birthweight and gestational age in fetal death records.
      METHODS: Using data from Georgia for 1989 and 1990, we detected singleton fetal
      death records having improbable or missing birthweight or gestational age by
      comparing these values with referent values. To verify the questionable values,
      we contacted 100 reporting hospitals in 1992. RESULTS: In 817 of 2226 records,
      values were either improbable (60.1%) or missing (39.9%). We were able to contact
      the hospitals to verify data for 716 (88%) of these records. Verification
      resulted in corrections to 405 (57%) records, and 48% of unreported birthweights
      were obtained. CONCLUSIONS: Many errors in recorded gestational age and
      birthweight were identified by this method. Rather than deleting or inputting
      problem data for analyses, researchers should consider efforts to verify them.
      Efforts to improve this information should include improved reporting, strict
      quality assurance, and procedures for routine verification and correction of
      records.

PMID- 9279270
TI  - Universal radiographic screening for tuberculosis among inmates upon admission to
      jail.
AB  - OBJECTIVES: This study evaluated the efficacy of radiographic screening for
      tuberculosis in correctional facilities. METHODS: Inmates at an admission
      facility in New York, NY, were screened for tuberculosis by registry cross-match,
      symptom interviews, tuberculin testing, and chest radiography. RESULTS: Thirty
      two cases of tuberculosis were detected among 4172 inmate admissions (767 cases
      per 100,000). Twenty-five inmates (78%) were previously diagnosed but
      incompletely treated; all were identified by registry cross-match. Seven inmates
      (22%) were newly diagnosed, of whom four (57%) were asymptomatic, had negative
      skin tests, and were detected only by their abnormal radiographs. CONCLUSIONS:
      Screening strategies that limit radiographic testing to inmates with either
      positive skin tests or symptoms may result in missed opportunities for diagnosing
      active tuberculosis.

PMID- 9279269
TI  - The effects of a 2-year physical education program (SPARK) on physical activity
      and fitness in elementary school students. Sports, Play and Active Recreation for
      Kids.
AB  - OBJECTIVES: This study evaluated a health-related physical education program for
      fourth- and fifth-grade students designed to increase physical activity during
      physical education classes and outside of school. METHODS: Seven schools were
      assigned to three conditions in a quasi-experimental design. Health-related
      physical education was taught by physical education specialists or trained
      classroom teachers. Students from these classes were compared with those in
      control classes. Analyses were conducted on 955 students with complete data.
      RESULTS: Students spent more minutes per week being physically active in
      specialist-led (40 min) and teacher-led (33 min) physical education classes than
      in control classes (18 min; P < .001). After 2 years, girls in the specialist-led
      condition were superior to girls in the control condition on abdominal strength
      and endurance (P < .001) and cardiorespiratory endurance (P < .001). There were
      no effects on physical activity outside of school. CONCLUSIONS: A health-related
      physical education curriculum can provide students with substantially more
      physical activity during physical education classes. Improved physical education
      classes can potentially benefit 97% of elementary school students.

PMID- 9279271
TI  - The impact of parental consent on the HIV testing of minors.
AB  - OBJECTIVES: This investigation assessed change in use of human immunodeficiency
      virus (HIV) testing by minors after removal of the parental consent requirement
      in Connecticut. METHODS: HIV counseling and testing records for 13- to 17-year
      olds who accessed publicly funded testing sites were analyzed. RESULTS: The
      number of visits increased by 44% from the 12-month period before the statutory
      change (n = 656) to the 12-month period thereafter (n = 965). The number of HIV
      tests increased twofold. Visits and tests of high-risk minors tripled.
      CONCLUSIONS: Minors should have the right to consent to HIV testing.

PMID- 9279272
TI  - Screening for adolescent smoking among primary care physicians in California.
AB  - OBJECTIVES: This study determined how often primary care physicians ask
      adolescents about smoking. METHODS: We surveyed a stratified random sample of
      community-based, board-certified California physicians, using a mailed
      questionnaire. RESULTS: Overall, physicians (n = 343; 77% response rate) screened
      younger adolescents for regular smoking during 71.4% (95% confidence interval
      [CI] = 67.9, 74.9) of routine physical exams and older adolescents during 84.8%
      (95% CI = 82.3, 87.4) of such visits. For acute-care visits, the screening rates
      were 24.4% (95% CI = 20.6, 28.1) for younger and 40.2% (95% CI = 36.4, 44.0) for
      older adolescents. Physicians asked 18.2% (95% CI = 15.2, 21.3) of younger and
      35.6% (95% CI = 32.0, 39.1) of older adolescents about experimental smoking.
      Screening varied by specialty. CONCLUSIONS: These data imply that physicians are
      missing opportunities to screen adolescents for smoking.

PMID- 9279273
TI  - Cigarette smoking attitudes and first use among third- through sixth-grade
      students: the Bogalusa Heart Study.
AB  - OBJECTIVES: This study examined cigarette smoking attitudes, peer and parental
      influence, and first use among children in southeastern Louisiana. METHODS: Data
      from 933 children in grades 3 through 6 in the Bogalusa Heart Study (1993 through
      1994) were analyzed. RESULTS: Fifteen percent of the children had tried smoking.
      Of these, 40% first smoked with a family member, and 46% obtained their first
      cigarette from a family member or from home. Correlates of ever having smoked
      were race, sex, having a best friend or family member who smoked, and attitudes
      that smoking is disgusting and that nonsmokers get better grades. CONCLUSIONS:
      Prevention programs should begin early and focus on family and peer influences as
      well as attitudes.

PMID- 9279274
TI  - Blood lead testing by pediatricians: practice, attitudes, and demographics.
AB  - OBJECTIVES: This study aimed to evaluate adherence and identify ways to improve
      concordance between blood lead testing guidelines and practice. METHODS: One
      hundred fifty-five pediatricians responded to a questionnaire assessing
      demographic, knowledge, and attitudinal factors relating to lead testing.
      RESULTS: Only 27% of the respondents adhered to the guidelines, and less than
      half knew all of the answers to three factual questions about the
      recommendations. Adherence was higher among physicians who knew the guidelines,
      were more recently trained, or had high proportions of Medicaid or minority
      patients. CONCLUSIONS: Physician education and financial incentives hold the most
      promise for increasing adherence to blood lead testing guidelines.

PMID- 9279275
TI  - Elevated blood lead levels in children of construction workers.
AB  - OBJECTIVES: This study examined whether children of lead-exposed construction
      workers had higher blood lead levels than neighborhood control children. METHODS:
      Twenty-nine construction workers were identified from the New Jersey Adult Blood
      Lead Epidemiology and Surveillance (ABLES) registry. Eighteen control families
      were referred by workers. Venous blood samples were collected from 50 children
      (31 exposed, 19 control subjects) under age 6. RESULTS: Twenty-six percent of
      workers children had blood lead levels at or over the Centers for Disease Control
      and Prevention action level of 0.48 mumol/L (10 micrograms/dL), compared with 5%
      of control children (unadjusted odds ratio = 6.1; 95% confidence interval = 0.9,
      147.2). CONCLUSIONS: Children of construction workers may be at risk for
      excessive lead exposure. Health care providers should assess parental occupation
      as a possible pathway for lead exposure of young children.

PMID- 9279276
TI  - The deterioration in children's nutritional status in rural Chad: the effect of
      mothers' influence on feeding.
AB  - OBJECTIVES: This study examined how maternal influence on child feeding modified
      the deterioration of child nutritional status in Chad. METHODS: The pattern of
      height with age was examined in 98 rural Chadian children aged 12 through 71
      months from 64 households randomly chosen. RESULTS: Younger children were more
      stunted than older ones, probably reflecting secular deterioration in weanlings'
      nutritional status from 1982 to 1987. Children of mothers with influence over
      child feeding were taller than children of mothers with less influence, but this
      held only for the youngest children. CONCLUSIONS: Height-for-age can be a useful
      indicator of recent changes in social and environmental effects on child health.
      The mother's influence may have buffered the negative impact of socioeconomic
      conditions on child growth.

PMID- 9279277
TI  - The effect of vitamin A supplementation on the growth of preschool children in
      the Sudan.
AB  - OBJECTIVES: This study assessed the effect of vitamin A supplementation at 6
      month intervals on child growth. METHODS: Sudanese children (n = 28,740) 6 to 72
      months of age were weighed and measured at baseline and at each of three follow
      up visits. RESULTS: Periodic vitamin A supplementation had no effect on the rate
      of weight or height gain in the total population or on the incidence of wasting,
      stunting, or wasting and stunting among children who were normally nourished at
      baseline. CONCLUSIONS: Reducing poverty and improving access to adequate diets
      should remain the goals of programs designed to improve the nutritional status of
      malnourished populations.

PMID- 9279280
TI  - The effect of a community-supported alcohol ban on prenatal alcohol and other
      substance abuse.

PMID- 9279278
TI  - The underreporting of deaths of American Indian children in California, 1979
      through 1993.
AB  - OBJECTIVES: This study linked birth and death certificates to determine
      misclassification of deaths of American Indian children in California. METHODS:
      Birth records for 1979 to 1993 were matched with mortality records through a
      computerized system. RESULTS: The number of deaths to American Indians was
      estimated to be three to four times greater than that reported on death
      certificates. Children in urban counties and those who died before 1987 were more
      likely to be misclassified. CONCLUSIONS: California death certificates identify
      less than one third of the deaths among American Indian children. Adjusting for
      racial misclassification provides a more accurate accounting of child mortality
      among American Indians.

PMID- 9279279
TI  - Mandatory parental involvement in minors' abortions: effects of the laws in
      Minnesota, Missouri, and Indiana.
AB  - OBJECTIVES: This study examined the effects of parental involvement laws on the
      birth rate, in-state abortion rate, odds of interstate travel, and odds of late
      abortion for minors. METHODS: Poisson and logistic regression models fitted to
      vital records compared the periods before and after the laws were enforced.
      RESULTS: In each state, the in-state abortion rate for minors fell (relative to
      the rate for older women) when parental involvement laws took effect. Data
      offered no empirical support for the proposition that the laws drive up birth
      rates for minors. Although data were incomplete, the laws appeared to increase
      the odds of a minor's traveling out of state for her abortion. If one judges from
      the available data, minors who traveled out of state may have accounted for the
      entire observed decline in the in-state abortion rate, at least in Missouri. The
      laws appeared to delay minors' abortions past the eighth week, but probably not
      into the second trimester. CONCLUSIONS: Several empirical arguments used against
      and in support of parental involvement laws do not appear to be substantiated.

PMID- 9279281
TI  - Public and private academic medical partnerships in improving nutritional
      management in phenylketonuria.

PMID- 9279282
TI  - Bottled water use in an immigrant community: a public health issue?

PMID- 9279283
TI  - Outercourse as a safe and sensible alternative to contraceptives.

PMID- 9279285
TI  - The interstitium in renal disease.

PMID- 9279284
TI  - Diagnosis and treatment of disease caused by nontuberculous mycobacteria. This
      official statement of the American Thoracic Society was approved by the Board of
      Directors, March 1997. Medical Section of the American Lung Association.
AB  - Diagnostic criteria of nontuberculous mycobacterial lung disease in HIV
      seropositive and -seronegative hosts. The following criteria apply to symptomatic
      patients with infiltrate, nodular or cavitary disease, or a high resolution
      computed tomography scan that shows multifocal bronchiectasis and/or multiple
      small nodules. A. If three sputum/bronchial wash results are available from the
      previous 12 mo: 1. three positive cultures with negative AFB smear results or 2.
      two positive cultures and one positive AFB smear B. If only one bronchial wash is
      available: 1. positive culture with a 2+, 3+, or 4+ AFB smear or 2+, 3+, or 4+
      growth on solid media C. If sputum/bronchial wash evaluations are nondiagnostic
      or another disease cannot be excluded: 1. transbronchial or lung biopsy yielding
      a NTM or 2. biopsy showing mycobacterial histopathologic features (granulomatous
      inflammation and/or AFB) and one or more sputums or bronchial washings are
      positive for an NTM even in low numbers. COMMENTS: these criteria fit best with
      M. avium complex, M. abscessus, and M. kansasii. Too little is known of other NTM
      to be certain how applicable these criteria will be. At least three respiratory
      samples should be evaluated from each patient. Other reasonable causes for the
      disease should be excluded. Expert consultation should be sought when diagnostic
      difficulties are encountered.

PMID- 9279286
TI  - The emergence of mouse models of atherosclerosis and their relevance to clinical
      research.
AB  - Due to the ability to introduce or mutate genes, the mouse has become the most
      common experimental animal model for atherosclerosis research. Wildtype mice on a
      chow diet do not get atherosclerosis. Three ways to induce atherosclerosis in
      mice are discussed: diet-induced, apoE deficiency-induced, and LDL receptor
      deficiency induced. The atherosclerotic lesions in apoE-deficient mice have been
      well characterized, and they resemble human lesions in their sites of
      predilection and progression to the fibroproliferative stage. These mouse models
      of atherosclerosis are being used to identify genes which modify atherosclerosis
      susceptibility and in the development of antiatherogenic therapies.

PMID- 9279287
TI  - Hyperkalaemia in acute leukaemia: a sign of adrenocortical insufficiency.
AB  - OBJECTIVES: To evaluate adrenal cortical reserve function in hyperkalaemic
      patients with acute leukaemia (AL). DESIGN: In hyperkalaemic AL patients, after
      basal blood collection for cortisol, rapid adrenocorticotropic hormone (ACTH)
      stimulation test was performed with human a1-24-ACTH 0.25 mg, intravenously.
      Sixty minutes following injection, additional plasma was obtained for cortisol.
      Normal response was a peak cortisol level greater than 15 micrograms dL-1 with an
      increment greater than 5 micrograms dL-1. SETTING: Hacettepe University Hospital,
      Ankara, Turkey. SUBJECTS: Newly diagnosed AL patients with plasma K+ values
      exceeding 4.5 mmol L-1, who had never received antileukaemia therapy were
      eligible for entry into the trial. Thirteen patients fulfilled these criteria.
      Twenty AL patients with normal serum K+ levels were studied as controls. RESULTS:
      In six patients with hyperkalaemia, adrenal cortical response to rapid ACTH test
      was inadequate. One patient died during induction chemotherapy due to sepsis.
      Five of the remaining patients entered remission. Repeat ACTH tests during
      remission revealed normalization of the adrenocortical function in these
      patients. However, in only one patient with normal serum K+ level, adrenocortical
      reserve was decreased. CONCLUSIONS: We suggest that in any AL patient with
      hyperkalaemia, adrenal reserve function should be evaluated with rapid ACTH
      stimulation test. In states of resistant hypotension and hyperkalaemia, steroids
      may be life saving.

PMID- 9279288
TI  - Reproducibility of on-line vectorcardiography measurements in patients with and
      without acute ischaemic heart disease.
AB  - OBJECTIVES: The aim of the present study was to determine inter and intraobserver
      variations of measurements with on-line vectorcardiography (VCG). DESIGN: The VCG
      registrations were evaluated by two independent observers. One observer also
      evaluated the VCG registrations on two separate occasions. Monitored VCG
      variables were: ST vector magnitude (ST-VM), ST vector lead X (ST-X), ST change
      vector magnitude (STC-VM) and QRS vector difference (QRS-VD). SUBJECTS: On-line
      VCG was performed for 24 hours in 60 patients (10 with low probability of
      ischaemic heart disease, 25 with unstable angina pectoris and 25 with acute
      myocardial infarction). RESULTS: A close correlation between the two observers
      and small coefficients of variation were found regarding the ST-VM initial value
      (r = 0.99, 4.7), the ST-X maximum depression (r = 0.99, 3.2) and the QRS-VD end
      value (r = 0.98, 5.6). A less close correlation and higher coefficients of
      variation were found regarding the number of QRS-VD episodes (r = 0.94, 41.5), ST
      VM episodes (r = 0.89, 37.8) and STC-VM episodes (r = 0.87, 35.1). Correlation
      coefficients and coefficients of variations for VCG measurements performed on two
      separate occasions by one observer ranged from 0.97 to 0.99 and from 18.1 to 1.8
      respectively. Three (12%) of 25 patients with acute myocardial infarction did not
      meet the VCG infarction criterion (QRS-VD > or = 15 microVs) by both observers.
      In addition, five (20%) of the 25 patients with unstable angina pectoris met the
      VCG infarction criterion by both observers. CONCLUSION: The inter and
      intraobserver variation for VCG interpretations was low, but the number of QRS
      VD, ST-VM and STC-VM episodes varied between the two observers. This finding
      suggests that additional training may improve the results. Caution is also
      recommended in using VCG to rule out or establish the diagnosis of acute
      myocardial infarction.

PMID- 9279289
TI  - Danaparoid: an antithrombotic agent without major impact on triglyceride
      hydrolysis capacity in humans.
AB  - OBJECTIVES: Heparin is a widely used antithrombotic drug. Besides its
      anticoagulant properties, it also has a marked influence on lipid metabolism, by
      decreasing serum lipolytic activity due to lipase depletion from vascular sites
      and stores. Especially in haemodialysis patients who receive heparin during every
      dialysis session, and in hypertriglyceridaemic patients, decreasing lipolytic
      activity can lead to the accumulation of triglyceride-rich lipoproteins, which
      are atherogenic. Replacement of heparin by an antithrombotic drug with less
      lipase releasing activity might reduce this risk. DESIGN: We tested danaparoid, a
      new antithrombotic drug, and compared its ability to displace biotinylated
      heparan sulphate from lipoprotein lipase in vitro with heparin. Furthermore we
      compared the in vivo lipase releasing activity. RESULTS: Danaparoid displaced
      significantly less biotinylated heparan sulphate from triglyceride-rich
      lipoprotein-lipoprotein lipase complexes in vitro than heparin. Intravenous
      injection of danaparoid released less than 20% (P < 0.05) of the lipolytic
      activity released by an equivalent anticoagulant dose of heparin. CONCLUSION:
      Danaparoid is the drug of choice during the antithrombotic therapy of
      hypertriglyceridaemic or haemodialysis patients.

PMID- 9279290
TI  - Health, health care utilization and living conditions in foreign-born diabetic
      patients in southern Sweden.
AB  - OBJECTIVES: To compare foreign- and Swedish-born diabetic subjects regarding
      health care utilization, complications, clinical and socio-economic
      characteristics. DESIGN: Cross-sectional study. SETTING: All known diabetic
      patients living in six defined primary health care districts. SUBJECTS: Of 1861
      identified subjects aged > 25 years 90.1%. 113 foreign- and 1564 Swedish-born
      subjects participated. Mean time of residence in Sweden was 32 +/- 1.2 years, 93%
      > 10 years. MAIN OUTCOME MEASURES: A standardized interview, a physical
      examination and an evaluation of medical records. RESULTS: No differences were
      found regarding living conditions or health care utilization, with the exception
      of higher use of home-care from public authorities in Swedish-born subjects (P <
      0.05) despite no difference in dependency on help according to Katz's ADL index.
      There were no major differences in objective health (glycaemic control and
      complications related to diabetes) with the exception of lower frequency of
      sensory neuropathy (P < 0.01) and peripheral vascular disease (P < 0.05) in
      foreign-born subjects. The prevalence of diabetes was 2.1% (95% CI 1.7-2.5) in
      the foreign-born and 2.6% (95% CI 2.5-2.7) in Swedes. Foreign-born individuals
      were five years younger (P < 0.001), were more often diagnosed > or = 30 years (P
      < 0.05), had a two years' shorter duration of disease (P < 0.001) and were less
      often treated with insulin (P < 0.01). Treatment with insulin was related to the
      duration and presence of complications related to diabetes. CONCLUSIONS: There
      were no major differences in objective health or use of health care in European
      migrants with diabetes mellitus, mainly Scandinavians, with short cultural
      distance and long residence in Sweden compared to Swedish-born diabetic patients.

PMID- 9279291
TI  - Efficacy and safety of human leucocyte interferon-alpha treatment in patients
      younger than 60 years of age with polycythaemia vera.
AB  - OBJECTIVES: To evaluate the therapeutic activity and toxicity of human leucocyte
      interferon-alpha (lIFN-alpha) in patients with polycythaemia vera (PV) aged less
      than 60 years. DESIGN: An open clinical study. SETTING: Department of Medical
      Sciences, Regina Apostolorum Hospital, Albano Laziale, and Chair of Haematology,
      University of Rome 'Tor Vergata', S. Eugenio Hospital, Rome, Italy. SUBJECTS:
      Fourteen patients with PV and aged < 60 years who had active disease as indicated
      by the need for phlebotomy and/or cytoreductive therapy. INTERVENTIONS: lIFN
      alpha administered subcutaneously at the starting dose of 3 MU thrice weekly. The
      interferon dose could be escalated to six MU thrice weekly if it was well
      tolerated and disease was not controlled after three months of treatment at the
      lower dose. MAIN OUTCOME MEASURES: Change in phlebotomy requirements, spleen
      size, pruritus score and haematological parameters after 6 months of treatment.
      Evaluation of lIFN-alpha side effects. RESULTS: Complete or partial disease
      control was achieved in 13 patients. Six patients achieved a complete response
      (CR) and four a partial response (PR) after 3 months of therapy. Dose escalation
      in partial or nonresponders resulted in two patients switching from a status of
      PR to CR, and three other patients achieving a partial response after being
      unresponsive to the lower dosage. Human leucocyte interferon-alpha therapy
      significantly improved (P < 01) phlebotomy requirements, the degree of
      splenomegaly, pruritus scores, iron stores and MCV values, and platelet and
      leucocyte counts. A mild flu-like syndrome (low-grade fever, nausea and myalgias)
      appeared during the early phase of therapy in the majority of patients, but no
      patient had to discontinue lIFN-alpha because of intolerance. CONCLUSIONS:
      Subcutaneous human leucocyte interferon-alpha appears an effective and well
      tolerated therapy in the management of PV-associated myeloproliferation and
      pruritus in patients aged less than 60 years.

PMID- 9279292
TI  - Chronic work stress is associated with atherogenic lipids and elevated fibrinogen
      in middle-aged men.
AB  - OBJECTIVES: To examine the association between a model of chronic work stress
      (high efforts in combination with low rewards) and two risk factors of coronary
      heart disease, low-density-lipoprotein (LDL)-cholesterol and fibrinogen. DESIGN:
      A cross-sectional study in a group of 179 healthy middle-aged (48.5 +/- 4.5) male
      middle managers. SETTING: A large car-producing enterprise in Germany. RESULTS:
      After adjustment for relevant covariates, logistic regression analysis showed
      independent effects of a composite measure of high effort and low reward at work
      on the prevalence of elevated (upper tertile, i.e. > or = 160 mg dL-1) LDL
      cholesterol (prevalence odds ratio (POR) = 3.57; 95% confidence intervals (CI):
      1.24-10.20) and on elevated (upper quintile, i.e. > or = 420 mg dL-1) plasma
      fibrinogen (POR = 6.71 (CI: 1.57-28.76). Apart from this core measure, cigarette
      smoking, overweight and alcohol consumption were the covariates with the
      relatively strongest contributions to the multivariate model. CONCLUSIONS:
      Results give preliminary evidence on an independent association of chronic work
      stress with atherogenic lipids and with elevated fibrinogen in an occupationally
      homogeneous group of healthy middle-aged men.

PMID- 9279293
TI  - Declining autopsy rate in Sweden: a study of causes and consequences in Malmo,
      Sweden.
AB  - OBJECTIVE: In Sweden there has been a continuous decrease in the autopsy rate
      during the last 15-20 years. The autopsy rate in the city of Malmo has declined
      from 81% in 1984 to 34% in 1993. The intention of this study was to improve our
      understanding of the causes of the decline, and to assess its consequences with
      regard to cause of death surveillance and case retrieval in epidemiological and
      clinical research. DESIGN: A retrospective study. SETTING: The University
      Hospital in Malmo, a city in southern Sweden with 230000 inhabitants. SUBJECTS:
      All deceased in 1984 (2900) and 1993 (3198). Cancer incidence 1984 and 1993. MAIN
      OUTCOME MEASURES: Changes in autopsy rate in relation to age, sex, place of death
      and cause of death 1984 and 1993. Changes in the distribution of underlying
      causes of death in cases submitted and not submitted for a post mortem 1984 and
      1993. Changes in cancer incidence and the number of incidentally-detected new
      tumours 1984 and 1993. RESULTS: Patients who died in nursing homes were less
      often sent for a post mortem than were patients who died at the hospital. From
      1984 to 1993 the percentage of people dying in nursing homes increased from 1 to
      29%. Care of the elderly has been reorganized, and the number of terminally ill
      patients who die in nursing homes has increased during the last 20 years in
      Sweden. This shift in place of death seems to be the single major explanation of
      the declining autopsy rate in Malmo. The overall autopsy rate in 1993 remained,
      however, lower than it was in 1984 when a shift in place of death was taken into
      account. During the period of study there was a decline in the autopsy rate at
      all departments within the hospital. The distribution of underlying causes of
      death according to the death certificates was similar in 1984 and in 1993.
      However, in cases not submitted for autopsy in 1993 there were greater
      proportions dying from pulmonary and circulatory diseases, respectively, than
      there were in 1984. The lower autopsy rate in 1993 was for several cancer sites
      also associated with a reduced number of new cancer cases. The percentage of
      tumours incidentally detected at autopsy went down in men from 40 to 19% and in
      women from 39 to 17%. CONCLUSION: Patients submitted for autopsy represented,
      with regard to age, sex, cause and place of death, a selected group of all
      deceased. The declining autopsy rate was associated with a difference in the
      distribution of underlying cause of death and of the incidence of cancer. It is
      concluded that the changes in the autopsy rate have to be taken into account in
      studies dealing with time trends of causes of death and incidence of cancer.

PMID- 9279294
TI  - Bambuterol raises high-density lipoprotein levels in patients with
      hyperlipidaemia.
AB  - OBJECTIVE: The objective of this study was to investigate the effects of
      bambuterol (a prodrug of the beta 2-agonist terbutaline) on lipid and lipoprotein
      levels in patients with hyperlipidaemia. Both these drugs are extensively used in
      the treatment of patients with bronchial asthma. Earlier studies in healthy
      volunteers and in patients with noninsulin dependent diabetes mellitus have shown
      that terbutaline and bambuterol increase HDL cholesterol levels, and therefore
      bambuterol might have beneficial effects on HDL levels in patients with
      hyperlipidaemia. DESIGN: The present study was a randomized, double-blind,
      crossover study, comparing 20 mg of bambuterol with placebo, each one given for 6
      8 weeks with a 3-4 week washout period in between. SETTING: The study was
      performed in an out-patient lipid clinic at Malmo University Hospital. SUBJECTS:
      Thirty-one patients with hyperlipidaemia (S-cholesterol > 6.5 mmol L-1 and S
      triglycerides > 2.0 mmol L-1) were included. MAIN OUTCOME MEASUREMENTS AND
      RESULTS: The results showed that bambuterol increased S-HDL cholesterol levels by
      7% (P = 0.012). Increases were 23% for P-HDL2 and 7% for P-HDL3 fractions, but no
      effect was apparent on S-apolipoprotein A-1 levels. CONCLUSION: This study
      suggests that the beta 2-agonist bambuterol might be used as an alternative or as
      a complement in the treatment of dyslipidemic patients, when an increase in HDL
      cholesterol is desired.

PMID- 9279296
TI  - Protection against cardiovascular collapse in an alcoholic patient with thiamine
      deficiency by concomitant alcoholic ketoacidosis.
AB  - Hyperlactataemia due to thiamine deficiency has so far only been reported in the
      setting of full-blown cardiovascular beriberi with congestive heart failure and
      systemic vasodilatation. Poor tissue oxygenation and impaired lactate clearance
      by the liver are generally accepted as underlying causes of the elevated lactate
      levels. We present an alcoholic patient with thiamine deficiency-induced
      hyperlactataemia and accompanying alcoholic ketoacidosis, who did not display the
      circulatory disturbances that are characteristic of cardiovascular beriberi. The
      hypothesis will be presented that the concomitant presence of alcoholic
      ketoacidosis has prevented haemodynamic deterioration. Putative mechanisms that
      could explain such an effect are discussed in detail, with special reference to
      the role of acetyl-CoA and adenosine.

PMID- 9279295
TI  - Guidelines and reported practice for the treatment of hypertension and
      hypercholesterolaemia.
AB  - OBJECTIVE: To monitor changes in family physicians' reported practice on
      hypertension and hypercholesterolaemia. DESIGN: Random samples of physicians were
      selected for telephone interviews on their practice regarding cut-off levels and
      pharmacological treatment of hypertension and hypercholesterolaemia, related to a
      case scenario of a 48-year-old man, in 1989, 1991 and 1993. SETTING: Primary care
      facilities in southern Sweden. SUBJECTS: Specialists in family medicine, employed
      in public primary health care. Participation rates were in 187/201 (93%) in 1989,
      236/264 (89%) in 1991 and 257/298 (86%) in 1993. MAIN OUTCOME MEASURES: Cut-off
      levels and drug treatment preferences for hypertension and hypercholesterolaemia.
      RESULTS: During the period 1989-1993, decreasing mean cut-off levels for
      pharmacological treatment of hypertension (P < 0.001) were reported, below the
      levels of the guidelines. Although betablockers were first choice drug in all
      three surveys, the proportion preferring this has diminished (P < 0.001), whilst
      the proportions preferring ACE-inhibitors and calcium channel blockers have
      increased (P < 0.001 and P = 0.02, respectively). For drug treatment of
      hypercholesterolaemia, the mean cut-off level remained close to guidelines in all
      three surveys. The proportion of physicians suggesting resins and nicotinic acid
      as first choice drug had decreased (P < 0.001 and P = 0.03, respectively), whilst
      the proportion preferring statins and fibrates had increased (P < 0.001 and P =
      0.048, respectively). CONCLUSION: Practice guidelines on hypertension and
      hypercholesterolaemia have not had the desired impact on physicians' reported
      practice. The reason for this might be that physicians did not value the
      guidelines as adequate tools for practice, or that the methods for dissemination,
      implementation, and maintenance of guidelines were not appropriate.

PMID- 9279297
TI  - Hyperthyroidism and pulmonary hypertension.
AB  - OBJECTIVES: To identify patients with hyperthyroidism and coincidental pulmonary
      hypertension and to document reversibility of pulmonary hypertension after
      treatment of hyperthyroidism. DESIGN: Patients with hyperthyroidism referred for
      transthoracal echocardiography for any reason that showed elevated pulmonary
      arterial pressures were collected. After therapy for the thyreotoxic state with
      documented normalization of thyroid hormone (IT4), pulmonary arterial pressure
      was measured again noninvasively. SETTING: An out-patient tertiary referral
      centre. SUBJECTS: The medical records were used to identify, retrospectively,
      patients with hyperthyroidism and pulmonary hypertension over a three-year period
      (April 1993 to April 1996). INTERVENTIONS AND MAIN OUTCOME MEASURES: Systolic
      pulmonary artery pressure (PAPs) was determined by adding up right ventricular
      systolic pressure (RVSP) and mean right atrial pressure (RAP) measured by
      continuous-wave Doppler echocardiography according to standard techniques. All
      patients were treated for hyperthyroidism to normal IT4 levels. After successful
      therapy. Doppler echocardiography was repeated. RESULTS: Four patients with
      pulmonary hypertension showing elevated PAPs of 40 +/- 11 mmHg were identified.
      After therapy. PAPs decreased in all patients to a mean of 25 +/- 6 mmHg.
      CONCLUSION: The observation of four patients with pulmonary hypertension and
      hyperthyroidism is striking and suggests a possible pathogenetic link of these
      disorders.

PMID- 9279298
TI  - Neurological effects associated with use of the insect repellent N,N-diethyl-m
      toluamide (DEET).
AB  - BACKGROUND: N,N-Diethyl-m-toluamide, an effective tick repellent, when applied to
      the skin, is the major component of essentially all of the products marketed for
      this purpose. It is used by about 30% of the US population, and by 23-29% of
      children in this population. Reports of neurologic adversity and death are rare
      and primarily involve children, but the dose relationship between N,N-diethyl-m
      toluamide exposure and the symptoms reported in the clinical literature is
      difficult to establish. METHODS: Animal toxicology studies, clinical reports of
      neurological adversities in children and adults, and the available Poison Control
      Center records have been reviewed in an effort to understand the relationship
      between the N,N-diethyl-m-toluamide exposure and reported adverse events.
      CONCLUSIONS: Based on (1) the animal toxicology database on N,N-diethyl-m
      toluamide, (2) the reports of adverse events in humans, and (3) the possible
      alternate etiologies for the symptoms reported in most patients, the risk of
      adversity from label-directed use of N,N-diethyl-m-toluamide appears low. Future
      efforts should focus on the prospective collection of adversity data with special
      attention paid to the documentation of clinical effects.

PMID- 9279299
TI  - Commentary--DEET: caution for children still needed.

PMID- 9279300
TI  - Placental transfer of N-acetylcysteine following human maternal acetaminophen
      toxicity.
AB  - OBJECTIVE: To determine whether the antidote for acetaminophen poisoning, N
      acetylcysteine, administered to pregnant women with acetaminophen toxicity,
      crosses the placenta and can be measured in the newborn circulation following
      delivery. DESIGN: Over a 15-month period, four pregnant women with acetaminophen
      toxicity, who delivered their infants while receiving the antidote N
      acetylcysteine, were studied. Maternal and cord blood from three viable infants,
      and cardiac blood sampled during an autopsy on the fourth, were analyzed for the
      presence of N-acetylcysteine using high-performance liquid chromatography.
      Maternal and cord blood aminotransferase activities, and autopsy findings on the
      nonviable infant were used to assess hepatic injury. RESULTS: N-Acetylcysteine
      was detected in the cord blood of three viable infants and in cardiac blood of a
      fourth, sampled at the time of autopsy. The mean N-acetylcysteine concentration
      in cord blood was 9.4 micrograms/mL (+/-1.3). This is well within the range
      associated with therapeutic doses of N-acetylcysteine typically administered to
      adults with acetaminophen poisoning. No adverse sequelae developed in the three
      viable infants. The fourth infant, delivered at 22 weeks gestational age died 3 h
      after birth. All mothers recovered and none of the four infants had evidence of
      acetaminophen-related toxicity. CONCLUSIONS: This is the first study documenting
      placental transfer of N-acetylcysteine in humans and provides impetus for
      research establishing a direct antidotal effect of N-acetylcysteine in the fetus.

PMID- 9279301
TI  - Zolpidem (Ambien): a pediatric case series.
AB  - BACKGROUND: In 1993, the nonbenzodiazepine sedative-hypnotic zolpidem tartrate
      (Ambien) was approved for use in the US. Zolpidem has an imidazopyridine
      structure and possesses a rapid onset of action and a short half-life. The toxic
      threshold and profile have not been well established in the pediatric population.
      METHODS: All pediatric zolpidem exposures reported to a regional poison
      information center over 24 months were reviewed retrospectively from the American
      Association of Poison Control Centers Toxic Exposure Surveillance System data
      collection forms. RESULTS: Twelve pediatric zolpidem exposures were reported.
      Seven were unintentional (ages 20 mon-5 y) and five were intentional
      misuse/suicide (ages 12-16 y). The regional poison information center was
      contacted within 1 h in ten cases with onset of symptoms within 10 to 60 min
      (mean 31.6 min). One child had no effect with 2.5 mg. As little as 5 mg caused
      symptoms with minor outcome in six unintentional ingestions (5-30 mg). Minor to
      moderate symptoms were reported 1-4 h after intentional ingestions (12.5-150 mg).
      The duration of symptoms in the unintentional cases ranged from less than 60 min
      up to 4 h (mean 2.4 h) and 6-10 h (mean 7.5 h) in the intentional exposures.
      Treatment consisted of observation (4), syrup of ipecac (1), lavage and activated
      charcoal (1), activated charcoal alone (5), and unknown (1). CONCLUSION: Due to
      the very rapid onset of central nervous system symptoms in children, emesis is
      not a treatment option. Supportive care, activated charcoal in large ingestions,
      and observation until symptoms resolve may be sufficient in most pediatric cases.

PMID- 9279302
TI  - Hypothermia from azithromycin?

PMID- 9279303
TI  - Do clinical pathways for major vascular surgery improve outcomes and reduce cost?
AB  - PURPOSE: This study was performed to determine whether the implementation of
      clinical pathways for patients who undergo major vascular procedures in a
      community hospital would shorten the length of stay and reduce charges when
      compared with Medicare standards. METHODS: Length of stay, hospital costs, and
      morbidity, mortality, and readmission rates for the four most common vascular
      diagnosis-related group (DRG) categories at our institution were compared with
      Medicare standards. The four categories were DRG 005 (extracranial vascular
      procedures), DRG 110 (aortic and renal procedures), DRG 478 (leg bypass with
      comorbidity), and DRG 479 (leg bypass without comorbidity). Between May 1, 1994,
      and June 30, 1996, 112 patients underwent carotid endarterectomy, 42 patients
      underwent aortic or renal procedures, and 130 patients underwent lower extremity
      bypass procedures (68% with comorbidity). Only Medicare patients were included
      because exact cost/reimbursement data were available. No admissions were
      excluded. RESULTS: The average length of stay was 1.2 days for DRG 005, 6.9 days
      for DRG 110, and 3.2 and 2.1 days for DRGs 478 and 479, respectively. The average
      cost savings when compared with the Medicare reimbursement was $4338 for DRG 005,
      $7161 for DRG 110, $4108 for DRG 478, and $2313 for DRG 479. Readmission was
      necessary for 9% of peripheral bypass patients. Ten percent of patients in DRG
      005 and 86% of patients in DRG 110 needed intensive care, whereas only 2% of
      patients who underwent complicated bypass procedures did. Ninety percent of
      carotid endarterectomy patients and 23% of leg bypass patients were discharged on
      the first postoperative day. There were two postoperative strokes (2%) after
      carotid surgery. Thirty-three percent of aortic/renal patients had complications
      that led to care outside the clinical pathway. Twenty-five percent of leg bypass
      patients required home care to treat open foot wounds. Total inpatient cost
      savings were $1,256,000 when compared with Medicare reimbursement. CONCLUSIONS:
      Clinical pathways significantly improve the length of stay and decrease inpatient
      charges for major vascular surgical procedures while maintaining high standards
      of care. Factors that favorably affected the length of stay and hospital charges
      were outpatient arteriography, same-day admission, early ambulation, physical
      therapy, home care, use of the intensive care unit on a selective basis, and
      early discharge. Factors that adversely affected these outcomes were emergency
      admission, inpatient arteriography, thrombolytic therapy, complications, and the
      need for dialysis or anticoagulation.

PMID- 9279304
TI  - Impact of a critical pathway on the results of carotid endarterectomy in a
      tertiary care university hospital: effect of methods on outcome.
AB  - PURPOSE: A carotid endarterectomy critical pathway (CP) targeting a 3-day
      postoperative course was introduced in March 1994. This retrospective analysis
      assesses its impact on operative results, postoperative length of stay (POD), and
      cost of hospitalization (COH). METHODS: One hundred eighty-six patients who
      underwent 201 carotid endarterectomy procedures from Nov. 1992 to Feb. 1994 (Pre
      CP; n = 67) and from Apr. 1994 to Jul. 1995 (Post-CP; n = 134) at Johns Hopkins
      Hospital, a tertiary care referral center, were evaluated. RESULTS: The Pre-CP
      and Post-CP groups had similar risk factors, postoperative morbidity rates, and
      mortality rates. Furthermore, they had similar mean POD (Pre-CP, 6.0 +/- 0.5
      days; Post-CP, 5.7 +/- 0.6 days; p = 0.79) and COH. However, only 85 of the Post
      CP (63%) patients were actually placed on the CP (CP-starters); the mean POD was
      3.4 +/- 0.3 days among these CP-starters (p < 0.0001) and 2.8 +/- 0.1 days among
      the 74 Post-CP patients (55%) that remained on the pathway (CP-finishers; p <
      0.0001). The mean COH was reduced from $12,881 (Pre-CP) to $9701 for the CP
      starters (p = 0.01) and to $8572 for the CP-finishers (p = 0.0001). However, we
      found that only 47 of the Pre-CP patients (70%) would have been eligible for the
      CP, and the mean POD among those cases was 4.2 +/- 0.4 days, which was not
      different than the mean POD among the CP-starters (p = 0.17). The mean COH of the
      eligible Pre-CP cases, $9508, was not significantly different from the COH of the
      CP-starters (p = 0.97). CONCLUSIONS: This subset analysis emphasizes the
      importance of establishing an accurate "control" group when studying a CP,
      because using all of the Pre-CP cases as the "control" group in the original
      analysis, including patients who would not have been candidates for the CP,
      clearly overstated the beneficial impact of the CP.

PMID- 9279305
TI  - Vascular surgeons' resource use at a university hospital related to diagnostic
      related group and source of admission.
AB  - PURPOSE: To determine whether differences in the conduct of individual practices
      of attending vascular surgeons account for variations in resource use at a
      university hospital. METHODS: The practice patterns of six attending vascular
      surgeons at the University of Michigan Hospital were assessed for patient length
      of stay (LOS), ancillary service use, and the number of nursing hours required.
      Included in the study were 1930 hospitalized patients who had one of the 10 most
      frequently encountered diagnostic related groups (DRGs). Statistical analyses of
      variables that were thought likely to affect resource use included multiple
      regression models. RESULTS: Patient age, sex, insurance, source of admission
      (direct admission or transfer admission), surgeon, and DRG category together
      accounted for 22% of LOS variation, 27.7% of variation in ancillary service use,
      and 29.4% of variation in nursing hours. In no model did the individual surgeon's
      practice significantly effect the LOS, ancillary use, or nursing hours. Patients
      transferred from other hospitals had increased resource use in all models. The
      DRG category alone explained 20.9% of the variance in LOS, 25.2% of the variation
      in ancillary service use, and 21.2% of the variance in nursing hours. CONCLUSION:
      Differences in the conduct of individual vascular surgeons' practices accounted
      for less than 1% variation in hospital resource use. The most important
      influences on resource use were the DRG category and the source of patient
      admission. Modification of the frequency and manner of accepting transfer
      patients to vascular surgery services of a university hospital may have a major
      impact on hospital resource use.

PMID- 9279306
TI  - Endovascular treatment of infrarenal abdominal aneurysms by the Stentor system:
      preliminary results of 79 cases. Stentor Retrospective Study Group.
AB  - PURPOSE: We report the initial French multicenter experience with the Stentor
      system in the endovascular treatment of AAAs. METHODS: Between May 1994 and March
      1996, 79 patients with AAAs were consecutively treated with an endovascular
      technique using the Stentor system. There were 71 bifurcated grafts and eight
      straight grafts. The patients were followed-up from 1 to 18 months (mean, 5.7
      months). Patient data and events were retrospectively analyzed. RESULTS: No
      patients was lost to follow-up. There were no surgical conversions. Four patients
      died after operation (4.8%). Two of them had been considered inoperable by the
      standard technique. Four patients (4.8%) had pulmonary complications, and three
      had colonic ischemia (3.7%). Forty-five patients (57%) had postoperative fever,
      and a transitory thrombocytopenia (10%) developed in eight patients. In 66
      patients (83%) the aneurysm was immediately excluded. The exclusion was
      definitive in 62 (78%). In 17 patients, there were 13 initial and six delayed
      endoleaks. In two of these patients, the initial endoleak sealed temporarily and
      resumed after 1 year of follow-up, requiring an additional straight, covered
      stent. Over all, seven of the leaks were treated successfully by an additional
      endovascular graft, one leak required a lumbar artery embolization, eight leaks
      sealed spontaneously, and one leak was untreated. During follow-up, there was no
      aneurysm rupture. Two patients died of unrelated causes. CONCLUSION: The Stentor
      system can safely and effectively exclude AAAs in the short term. Careful follow
      up is required to detect any delayed endoleak, and long-term results are awaited
      to confirm the efficacy of the method in preventing AAA rupture.

PMID- 9279307
TI  - Endovascular grafts for noninfected aortoiliac anastomotic aneurysms.
AB  - PURPOSE: This report describes our experience with endovascular repair of aortic
      and iliac anastomotic aneurysms. METHODS: Between June 1994 and March 1996, 12
      noninfected aortic or iliac anastomotic aneurysms in 10 patients who had serious
      comorbid medical conditions that precluded or made difficult standard operative
      repair were treated using endovascular grafts. No patient in this study had a
      history of fever, leukocytosis, or computed tomographic evidence of a
      periprosthetic fluid collection that was suggestive of infection of the original
      graft. Endovascular grafts composed of polytetrafluoroethylene and balloon
      expandable stents were introduced through a femoral arteriotomy and were placed
      using over-the-wire techniques under C-arm fluoroscopic guidance. RESULTS:
      Endovascular grafts were successfully inserted in all patients with aortic or
      iliac anastomotic aneurysms. There were no procedure-related deaths, and
      complications included one postprocedure wound hematoma and one perioperative
      myocardial infarction. Graft patency has been maintained for a mean of 16.1
      months, with no computed tomographic evidence of aneurysmal enlargement or
      perigraft leakage. CONCLUSIONS: Endovascular grafts appear to be a safe and
      effective technique for excluding some noninfected aortoiliac anastomotic
      aneurysms in high-risk patients and may become a treatment option in all patients
      who have clinically significant lesions.

PMID- 9279308
TI  - Chronic intraaneurysmal pressure measurement: an experimental method for
      evaluating the effectiveness of endovascular aortic aneurysm exclusion.
AB  - PURPOSE: To evaluate and compare the intraaneurysmal pressure (IAP) after
      exclusion using two different endovascular grafts. METHODS: Eight mongrel dogs
      had a 3 x 3 cm polytetrafluoroethylene (PTFE) aneurysm sewn as an interposition
      graft of the infrarenal aorta. A pressure transducer implanted into the aneurysm
      wall permitted continuous electronic IAP monitoring. Four aneurysms were excluded
      with a transluminally placed endovascular graft made of a PTFE graft and two
      Palmaz stents (PTFE-EG), three were excluded with a tantalum-Dacron endovascular
      graft (TD-EG), and one was surgically treated with a standard PTFE graft (PTFE
      Surg). The dogs were observed for 18 to 50 days (mean, 37.5 days) and were
      evaluated after surgery with duplex and spiral computed tomographic scans.
      RESULTS: All grafts successfully excluded the aneurysms without perigraft
      channels or leaks as documented by arteriogram and duplex and computed
      tomographic scans. The mean IAPs after repair with all PTFE-EGs were
      significantly lower (p < 0.001) than the mean systemic pressures. In addition,
      the mean IAP reduction was significantly greater (p < 0.005) in the PTFE-EG group
      than in the TD-EG group. CONCLUSIONS: Aneurysm exclusion with PTFE-EG
      significantly lowered IAP, did so significantly better than the TD-EG, and
      approached the IAP reduction obtained by standard repair. Such pressure reduction
      is necessary for effective protection against aneurysm rupture.

PMID- 9279309
TI  - Computed tomographic angiographic imaging of abdominal aortic aneurysms:
      implications for transfemoral endovascular aneurysm management.
AB  - PURPOSE: To describe anatomic features pertinent to patient selection and graft
      design for transfemoral endovascular aneurysm management (TEAM) of the infrarenal
      aorta using computed tomographic (CT) angiography. METHODS: A prospective
      noncomparative analysis of 102 spiral CT scans of the abdominal aorta of patients
      with abdominal aortic aneurysms was performed. From the original CT data set,
      slices were reconstructed perpendicular to the vessel axis (central lumen line)
      at a 10 mm interval. In these reconstructed slices, diameter measurements were
      performed. Vessel length was measured along the central lumen line. In each
      patient possibilities for TEAM were analyzed. RESULTS: Because of technical
      reasons, 36 scans were excluded from the analysis. Of the remaining 66 patients,
      18 could potentially be treated with a bifurcated endovascular device. The
      infrarenal aortic diameter-to-iliac artery diameter ratio was less than 2 in most
      patients. The vessel segments judged to be adequate for endovascular graft
      anchoring had a noncylindrical shape in the majority of cases. CONCLUSION: Only a
      minority of patients with abdominal aortic aneurysms can at this stage be treated
      with an endovascular graft. The ideal endovascular graft should be a combination
      of rigid and flexible components. The proximal and distal attachment systems
      should have some flexibility with an intrinsic maximum diameter while the
      midsection of the graft can be relatively rigid.

PMID- 9279311
TI  - Abdominal aortic aneurysm: a general defect in the vasculature with focal
      manifestations in the abdominal aorta?
AB  - PURPOSE: It has been suggested that abdominal aortic aneurysms (AAA) develop as a
      result of an alteration in the systemic connective tissue metabolism. This might
      change wall mechanics and diameter, not only in the AAA but also in the rest of
      the vascular system. This hypothesis was tested by studying the mechanical
      properties of AAAs as well as the common carotid artery (CCA) in the same patient
      population. METHODS: AAA and carotid artery stiffness (beta) was studied in 121
      individuals (101 men, 20 women) who were admitted for elective repair of AAA.
      Stiffness (beta) was calculated from diameter and pulsatile diameter change
      determined noninvasively from an ultrasonic echo-tracking system and blood
      pressure obtained by the auscultatory method. The results were compared with
      those of healthy individuals of corresponding age and gender published elsewhere.
      RESULTS: The stiffness of the AAA was increased in both men and women (p =
      0.0001). The increase was more pronounced in women compared with men (p = 0.0003)
      to a mean of 435% and 189% of the normal predicted values, respectively. In the
      CCA, the stiffness was increased in men (p = 0.027) and in women (p = 0.0001) to
      a mean of 131% and 149% of the normal predicted values, respectively. A
      significant correlation between stiffness in the aneurysm and in the carotid
      artery was seen (p = 0.0031). The carotid diameter was unchanged in men (p =
      0.924) and in women (p = 0.070) if adjusted for the difference in blood pressure
      between the individuals with AAAs and control subjects. There was no correlation
      between stiffness and diameter of the aneurysm in men (r = 0.16, p = 0.119) nor
      in women (r = 0.12, p = 0.598). CONCLUSIONS: This investigation demonstrated
      altered mechanical properties of the aneurysmal wall as well as in the CCA in
      individuals with AAAs. The normal age- and gender-related differences seen in the
      healthy aorta and CCA vanished. The results suggest that AAA is a generalized
      process of the vasculature with focal manifestation in the abdominal aorta.

PMID- 9279310
TI  - Morphologic assessment of abdominal aortic aneurysms by spiral computed
      tomographic scanning.
AB  - PURPOSE: The aim of this study was to seek a relationship between the morphologic
      features of abdominal aortic aneurysms and the feasibility of endoaortic
      grafting. METHODS: Between June 1995 and January 1996, 86 patients were
      prospectively studied with contrast-enhanced spiral computed tomographic scans,
      which provided 35 parameters concerning the aorta and iliac arteries. Four groups
      were established according to the diameter of abdominal aortic aneurysms: group
      A, 40 to 49 mm, 36 patients; group B, 50 to 59 mm, 26 patients; group C, 60 to 69
      mm, 10 patients; and group D, greater than 70 mm, 14 patients. RESULTS: There was
      a correlation between the diameter and length of the aneurysm (p < 0.0001) and
      between aneurysm diameter and length of the proximal neck (p < 0.001). Presence
      of a proximal neck or a distal neck was more frequent in groups A and B than in
      groups C and D (p < 0.01). The feasibility of endovascular grafting was estimated
      at between 50% and 61.6% and was higher in groups A and B than in groups C and D
      (p < 0.01). CONCLUSIONS: This study has shown an inverse relationship between the
      diameter of the aneurysm and the length of the aortic neck (correlation
      coefficient, -0.3640, p < 0.001). The diameter of an aneurysm was the most useful
      of the 31 parameters measured in predicting the feasibility of endoaortic
      grafting, estimated at 71% for aneurysms less than 60 mm in diameter and 37.5%
      for aneurysms greater than 60 mm in diameter (p < 0.01).

PMID- 9279312
TI  - Efficacy of subfascial endoscopy in eradicating perforating veins of the lower
      leg and its relation with venous ulcer healing.
AB  - PURPOSE: The purpose of this study was to investigate the efficacy of subfascial
      endoscopy by use of a mediastinoscope in the identification and ligation of
      incompetent perforating veins in patients with venous ulceration of the lower
      leg. METHODS: All patients who underwent subfascial endoscopy for venous
      ulceration between Jan. 1, 1994, and Mar. 1, 1995, at the Sint Franciscus
      Gasthuis in Rotterdam underwent duplex ultrasound scans of the lower leg before
      and 6 weeks after operation. The number and localization of the perforating veins
      on the mediodorsal side were compared with the findings during subfascial
      endoscopy. RESULTS: In 20 patients, preoperative duplex examination showed 46
      incompetent and six competent perforating veins. During operation the site of 43
      incompetent and all competent perforating veins was confirmed. Five additional
      perforating veins were found at operation (false-negatives). Postoperative duplex
      ultrasound scans showed six incompetent perforating veins (four persisting and
      two recurring perforating veins) in four patients, of which the ulcers did not
      heal in three. The ulcers of the other 17 patients healed. CONCLUSIONS:
      Subfascial endoscopy is an efficient technique in identifying incompetent
      perforating veins in patients with chronic ulceration of the lower leg. The
      persistence of incompetent perforating veins is related to failure of ulcer
      healing.

PMID- 9279313
TI  - Hemodynamic assessment of femoropopliteal venous reflux in patients with primary
      varicose veins.
AB  - PURPOSE: The aim of this study was to assess the anatomic distribution and extent
      of deep venous reflux in patients with primary varicose veins (PVVs) and to
      investigate its influence on venous hemodynamics. METHODS: Femoropopliteal venous
      reflux was examined using duplex color Doppler ultrasonography in 356 limbs with
      PVVs in 240 patients. Photoplethysmography (PPG) was performed using above-knee
      and below-knee tourniquets to determine the contributions of deep and superficial
      venous insufficiency. RESULTS: Of 356 limbs with PVVs, 61 (17.1%) had
      femoropopliteal venous reflux, 42 (11.8%) had superficial femoral venous reflux
      alone, and 57 (16.0%) had popliteal venous reflux alone. Femoropopliteal venous
      reflux was associated significantly with clinical symptoms and shortened the half
      venous refilling time measured by PPG, especially in the presence of incompetent
      perforating veins. These findings were obtained regardless of the presence of
      long saphenous vein reflux. CONCLUSIONS: Femoropopliteal venous reflux associated
      with PVVs plays an important role in the pathophysiologic mechanism of venous
      stasis and influences venous hemodynamics in the presence of incompetent
      perforating veins and short saphenous vein.

PMID- 9279314
TI  - Leukocyte activity in the microcirculation of the leg in patients with chronic
      venous disease.
AB  - PURPOSE: It has been suggested that leukocyte trapping and activation in the
      microcirculation of the leg skin causes lipodermatosclerosis and ulceration in
      patients with chronic venous disease. Ambulatory venous hypertension is accepted
      as the physiologic factor that leads to ulceration. We investigated leukocyte
      endothelial adhesion in patients who were subjected to short-term venous
      hypertension. METHODS: Two groups of patients with venous disease were studied:
      group 1, varicose veins with skin changes (n = 15); and group 2, varicose veins
      without skin changes (n = 15). Blood samples were taken from a foot vein before
      and after standing for 30 minutes to raise the venous pressure in the lower limb,
      and after lying supine again for 10 minutes. The samples were analyzed for
      leukocyte surface CD11b and L-selectin (CD62L) expression using a flow cytometer.
      Plasma-soluble L-selectin was also measured using an enzyme-linked immunosorbent
      assay. RESULTS: In patients with skin changes, median neutrophil CD11b levels
      fell from 4.66 to 3.83 arbitrary units (p = 0.005, Wilcoxon) after 30 minutes of
      venous hypertension, Median monocyte CD11b levels fell from 7.65 to 5.8 arbitrary
      units (p = NS, Wilcoxon) after venous hypertension and then fell further to 5.43
      arbitrary units (p = 0.02 vs baseline; Wilcoxon) when the venous hypertension was
      removed. Neutrophil and monocyte L-selectin levels also fell in response to
      venous hypertension, remaining low even after venous hypertension was removed. A
      similar pattern was seen in patients with uncomplicated varicose veins. There was
      a rise in soluble L-selectin in the plasma of both groups of patients after
      venous hypertension, reflecting leukocyte adhesion to endothelium. In the group
      of patients with skin changes the level of soluble L-selectin rose from 695 ng/ml
      to 836 ng/ml (p = 0.02, Wilcoxon), and in the group without skin changes the rise
      was from 700 ng/ml to 801 ng/ml (p = 0.02, Wilcoxon). CONCLUSION: Venous
      hypertension results in sequestration of the more activated population of
      neutrophils and monocytes in the microcirculation of the leg in patients with
      venous disease. These cells bind to the endothelium, releasing L-selectin, and do
      not emerge from the limb when venous hypertension is reversed. These findings do
      not differ between patients with varicose veins and those with skin changes.

PMID- 9279315
TI  - Hemostatic efficacy of a fibrin sealant-based topical agent in a femoral artery
      injury model: a randomized, blinded, placebo-controlled study.
AB  - PURPOSE: The efficacy of currently available topical hemostatic agents requires
      the formation of fibrin generated from circulating blood. Fibrin sealant, which
      is prepared from high concentrations of thrombin and fibrinogen, has been used in
      liquid form to promote hemostasis during vascular surgery. In a blinded,
      randomized, placebo-controlled fashion, we evaluated a dry dressing of purified,
      viral-inactivated human fibrinogen and human thrombin in a large animal model of
      arterial injury. METHODS: Dressings were prepared by application of a layer of
      lyophilized human fibrin sealant or immunoglobulin G (IgG, control) to a silicone
      backing material. Six anesthetized female Yorkshire pigs (16 to 27 kg) received
      bilateral, 4 mm longitudinal femoral arteriotomies after surgical exposure of the
      arteries. The arteriotomies were not closed. In each animal a fibrin sealant
      dressing was applied to one artery and a control dressing to the other. Each
      dressing was secured on the arteriotomy by a mechanical device. After application
      of the dressings, blood flow was restored to each limb for 1 hour. The
      compressive device was released for 5 seconds at intervals of 15 minutes to
      assess hemostasis. Blood flow was measured distal to each arteriotomy with a dual
      channel flowmeter to adjust equal bilateral compression. RESULTS: Blood loss
      (mean +/- SEM) was significantly less from the arteriotomy treated with the
      fibrin-based dressing compared with the control dressing (4.9 +/- 4.0 ml versus
      82.3 +/- 11.1 ml; p = 0.0005). Complete hemostasis was achieved at the first 15
      minute interval in five of six arteriotomies treated with fibrin sealant and in
      none of the six control arteriotomies during 1 hour of assessment (p = 0.03).
      Blood flow through each femoral artery at baseline was the same in both treatment
      and control arteries (fibrin sealant, 114.2 +/- 17.4 ml/min; control, 106.7 +/-
      16.5 ml/min; p = 0.24) and was not significantly different throughout the
      experiment. CONCLUSIONS: Fibrin-based dressings provide effective hemostasis in a
      large animal model of arterial injury. Further development of these dressings
      will address optimal formulation and configuration for clinical use. Our results
      suggest that fibrin-based dressings will be effective in promotion of hemostasis
      in arterial bleeding, without compromising blood flow.

PMID- 9279316
TI  - Popliteal artery compression and force of active plantar flexion in young healthy
      volunteers.
AB  - PURPOSE: To define the prevalence of popliteal artery occlusion during active
      plantar flexion in normally active and highly trained young volunteers by
      measuring plantar flexion force and to assess the force level associated with
      popliteal artery occlusion. METHODS: Eighty-four limbs of 42 healthy subjects
      were studied. Eighteen subjects were highly trained athletes, and 24 were
      normally active persons. Plantar flexion was progressively performed in prone
      position against a scale. Plantar flexion force was measured in kilograms. After
      determination of the maximum strength (Pmax) of plantar flexion force, the level
      necessary to occlude the popliteal artery (Poccl) was assessed by continuously
      monitoring that vessel using color duplex sonography. RESULTS: Occlusion of the
      popliteal artery during plantar flexion was observed in 88.1% of the subjects and
      77.4% of the limbs. No significant differences in prevalence were found between
      athletes and normally active subjects. The popliteal artery occluded at a mean
      plantar flexion force of 45.1 +/- 11.5 kg, which corresponded with 70.1% +/-
      16.8% of the maximum force exerted during the provocation test. Poccl was not
      significantly different between lower limbs of athletes and nonathletes. Although
      in lower limbs of athletes the popliteal artery occluded at a significantly lower
      relative force as compared with normally active subjects (65.6% +/- 17.4% vs
      74.5% +/- 17.4% of Pmax; p < 0.02), the difference was a result of two extremely
      low values found in a female athlete. CONCLUSION: Positional occlusion of the
      popliteal artery during active plantar flexion is commonly found in young healthy
      volunteers. Prevalence of the phenomenon depends on the force level exerted
      during active plantar flexion. Popliteal artery occlusion during active plantar
      flexion is not more frequent in athletes and occurs at a similar force level than
      in normally active subjects.

PMID- 9279317
TI  - Importance of diastolic velocities in the detection of celiac and mesenteric
      artery disease by duplex ultrasound.
AB  - PURPOSE: To assess the predictive value of ultrasound duplex scanning in the
      detection of superior mesenteric artery (SMA) and celiac artery (CA) occlusive
      disease. METHODS: Thirty-nine patients in whom mesenteric ischemia was suspected
      were examined with duplex scan and arteriography. RESULTS: Duplex scan visualized
      both vessels in all examined patients. An absent Doppler signal from an
      adequately visualized SMA or CA was a pathognomonic sign for total occlusion of
      the arteries. Elevated diastolic velocities (peak diastolic velocity > 70 cm/sec
      for SMA and > 100 cm/sec for CA) were accurate predictors of arteriographically
      confirmed stenoses > or = 50%. Increased blood velocity was occasionally observed
      in a thyrotoxic patient with malabsorption-induced weight loss and abdominal pain
      but arteriographically-normal SMA. Further examinations of hyperthyroid patients
      showed systematic elevation of peak systolic velocity in the SMA greater than 300
      cm/sec but normal diastolic velocities and resistivity indexes. CONCLUSION:
      Duplex ultrasound is a highly selective and specific method for detection of SMA
      and CA occlusive disease. The most accurate predictors of the disease were
      increased diastolic velocities, which in contrast to peak systolic velocity also
      correctly classified thyrotoxic patients. The method can be used before
      arteriographic evaluation as a screening examination of patients in whom
      mesenteric ischemia is suspected.

PMID- 9279318
TI  - Photodynamic therapy inactivates extracellular matrix-basic fibroblast growth
      factor: insights to its effect on the vascular wall.
AB  - PURPOSE: Photodynamic therapy (PDT), the light activation of photosensitizer dyes
      for the production of oxygen and other free radical moieties without the
      generation of heat, has been shown to inhibit the development of experimentally
      induced intimal hyperplasia. The host response to PDT, a form of vascular injury
      that results in complete vascular wall cell eradication, is devoid of
      inflammation and proliferation and promotes favorable vascular wall healing.
      These effects do not result in intimal hyperplasia and are suggestive of PDT
      induced changes in the extracellular matrix (ECM). As a model to better
      understand the biologic consequences of PDT on the vascular wall matrix proteins,
      the effect of PDT was studied on the powerful matrix-resident mitogen basic
      fibroblast factor (bFGF) in vitro. METHODS: PDT (5 to 200 J/cm2, 100 mW/cm2, 675
      nm) was used with the photosensitizer chloroaluminum sulfonated phthalocyanine (5
      micrograms/ml) to inactivate bFGF in vitro while 100 J/cm2 of irradiation was
      administered 24 hours after 5 mg/ml of the photosensitizer was used in vivo. PDT
      was used on bFGF in solution and on endothelial cell-derived ECM. Enzyme-linked
      immunosorbent assay was used to quantitate bFGF in solution after PDT treatment
      or after extraction from the ECM by collagenase and heparin. Functional activity
      of matrix-associated bFGF was assessed by smooth muscle cell mitogenesis by 3H
      thymidine incorporation. To demonstrate the in vivo relevance of these
      observations, immunohistochemical analysis of PDT-treated rat carotid arteries
      was undertaken. RESULTS: PDT eliminated detectable levels of bFGF in solution.
      PDT of ECM significantly reduced matrix-bound bFGF (1.0 +/- 0.6 vs 27.5 +/- 1.3
      pg/ml; p < 0.0001). This reduction in bFGF after PDT of the ECM was associated
      with a decrease in vascular smooth muscle cell mitogenesis (52.4% +/- 4.6%; p <
      0.0001) when plated on PDT-treated matrix compared with nontreated matrix.
      Quantitative replenishment of exogenous bFGF to PDT-treated matrix restored
      proliferation to baseline levels. PDT of rat carotid arteries demonstrated a loss
      of bFGF staining compared with control nontreated arteries. CONCLUSIONS: PDT
      inactivation of matrix-resident bFGF and possibly other bioactive molecules can
      provide a mechanism by which PDT suppresses smooth muscle cell proliferation in
      the vessel wall. This free radical-mediated alteration of matrix may contribute
      to favorable vascular healing when PDT is used for the inhibition of injury
      induced intimal hyperplasia.

PMID- 9279319
TI  - Therapeutic angiogenesis: a comparative study of the angiogenic potential of
      acidic fibroblast growth factor and heparin.
AB  - PURPOSE: Acidic fibroblast growth factor (aFGF) is a potent mitogen for vascular
      and other mesenchymal cells in vitro that can induce angiogenesis in vivo.
      Although heparin has no mitogenic potential of its own, it is an important aFGF
      cofactor in vitro and may also be capable of stimulating angiogenesis. Because
      the development of a collateral vasculature in response to ischemia appears to be
      dependent on angiogenesis, we compared the abilities of aFGF with or without
      heparin and heparin alone to accelerate angiogenesis in a rat hind limb ischemia
      model. METHODS: Daily subcutaneous injections of saline solution (1 ml), heparin
      (0.05 mg), or human recombinant aFGF with or without heparin (1 microgram aFGF,
      0.05 mg heparin) were administered into the hind limb region distal to the point
      of unilateral femoral artery ligation in the rat for the 10 days immediately
      after vascular occlusion. Angiogenicity was determined by histologic assessment
      of treatment outcomes. RESULTS: Histologic assessment of the number of vessels
      per microscopic field 10 days after vascular ligation in the fibrofatty tissues
      distal to the ligation point had the following results: saline solution, 10 +/- 4
      vessels; heparin, 13 +/- 4 vessels (p < 0.05 vs saline solution); aFGF, 26 +/- 8
      vessels; and aFGF/heparin 36 +/- 8 vessels (aFGF, aFGF/ heparin, p < 0.001 vs
      saline solution). Similar increases in vascularization were also noted in the
      skeletal muscle tissues distal to the vascular ligation point.
      Immunohistochemical analysis for the presence of proliferating cell nuclear
      antigen, a marker for mitogenic activity, demonstrated corresponding increases in
      proliferating cell nuclear antigen labeling for each of the treatment groups,
      expressed as a percentage of total vascular cell nuclei, as follows: saline
      solution, 7% +/- 2%; heparin, 21% +/- 8% (p < 0.05 vs saline solution); aFGF, 67%
      +/- 9%; and aFGF/heparin, 83% +/- 5% (aFGF, aFGF/heparin, p < 0.001 vs saline
      solution). CONCLUSIONS: The increased vascularization and mitogenic activity
      demonstrated by these respective studies suggest that angiogenesis is
      significantly accelerated by the administration of heparin alone and is
      accelerated to a greater extent by the administration of aFGF with or without
      heparin. The aFGF/heparin regimen may represent an optimal means of augmenting
      collateral vessel growth to relieve ischemia in the clinical setting.

PMID- 9279320
TI  - Molecular cloning of the complementary DNA for an additional member of the family
      of aortic aneurysm antigenic proteins.
AB  - PURPOSE: We have purified and partially sequenced a protein from the adventitia
      of the human aorta (aortic aneurysm antigenic protein 40 kDa; AAAP-40) that has
      homologies to bovine aortic microfibril-associated glycoprotein (MAGP-36). It is
      immunoreactive with immunoglobulin G (IgGs) purified from the serum and aortic
      wall of patients with abdominal aortic aneurysms. AAAP-40 and MAGP-36 have
      fibrinogen-like and vitronectin-like motifs. Screening an expression library
      constructed from human aortic adventitial messenger RNA has resulted in the
      cloning of three complementary DNAs whose gene products are immunoreactive with
      immunoglobulin G from patients with abdominal aortic aneurysms. Two strongly
      resemble each other and have been described separately. The purpose of this
      article is to report the third clone. METHODS: Messenger RNA from a specimen of
      human aortic aneurysmal adventitia was reverse-transcribed for insertion into the
      phagemid Uni Zap XR (Stratagene). A strain of Escherichia coli, engineered for
      expression (XL 1-Blue MFR', Stratagene), was transfected, and rabbit antihuman
      vitronectin antibody as used to identify positive clones. Sequencing of the
      positive clones was performed by the Core Laboratories at Columbia University.
      RESULTS: The hypothetical protein of rAAAP-CL4 (clone 4) shares sequence motifs
      with known microfibril-associated glycoproteins (MAGPs). The recombinant protein
      (rAAAP-CL4) is immunoreactive with serum from patients (three of four abdominal
      aortic aneurysm sera). In addition, similarities have been detected with
      immunoglobulins of the kappa family and with a protein from cytomegalovirus that
      is a potential molecular mimic. CONCLUSIONS: There may several members of a novel
      family of human aortic autoantigenic proteins implicated in abdominal aortic
      aneurysm disease.

PMID- 9279321
TI  - Nitric oxide mediates hyperglycemia-induced defective migration in cultured
      endothelial cells.
AB  - PURPOSE: To examine the effects of elevated glucose on the migration and
      proliferation of vascular endothelial cells in an in vitro wound model and to
      investigate whether nitric oxide (NO) mediates the effects of elevated glucose.
      METHODS: Migration was investigated in monolayers of bovine aortic endothelial
      cells wounded by scraping and measuring the distance, the number of cells
      migrating, and the area covered by the migrating cells in the presence of various
      concentrations of glucose. The effects of NO were evaluated by adding to the
      cultures NG-monomethyl arginine (NMMA), an inhibitor of NO synthase, or S
      nitrosylated penicillamine, which is a slow-release agent of NO. Proliferation
      was investigated in the presence of various concentrations of serum, glucose, or
      both. RESULTS: Elevated glucose levels (16.5 and 27.7 mmol/L) inhibited
      endothelial cell migration in a dose-dependent manner compared with cells
      cultured in the presence of 5.5 mmol/L glucose. Inhibition of migration was also
      observed when wounded mono-layers cultured in 5.5 mmol/L glucose were treated
      with S-nitrosylated penicillamine, which generates NO. Inhibition of NO synthase
      by NMMA prevented the inhibition of migration observed in media containing 27.7
      mmol/L glucose. Elevated glucose levels did not affect cell proliferation except
      in the presence of 20% fetal bovine serum. CONCLUSIONS: An elevated glucose level
      inhibits endothelial cell migration in an in vitro wound model, and the
      inhibition appears to be mediated by increased levels of NO.

PMID- 9279323
TI  - Gastroesophageal tumor embolization to the popliteal arteries.
AB  - Arterial tumor embolization is an unusual cause of acute arterial occlusion and
      is reported primarily in the oncologic literature. We report a case of acute
      bilateral popliteal artery emboli from adenocarcinoma of the distal esophagus.
      Arterial tumor emboli are infrequent but should be considered in the differential
      diagnosis by the vascular surgeon caring for patients with malignancy.

PMID- 9279322
TI  - Mitogen-activated protein kinase activation: an alternate signaling pathway for
      sustained vascular smooth muscle contraction.
AB  - PURPOSE: The vascular smooth muscle determines the dynamic caliber of the blood
      vessel and hence is the final effector cell in modulating vasomotor tone.
      Although considerable information is available regarding the physiologic agonists
      that induce contraction, less is known about the cellular signaling events that
      lead to long-lasting contractions or vasospasm. We examined the hypothesis that
      activation of mitogen-activated protein (MAP) kinase may be associated with
      sustained smooth muscle contractions. METHODS: Physiologic contractile responses
      were determined in intact bovine carotid artery smooth muscles in a muscle bath.
      Corresponding signaling events were determined with immunoblots using
      antiphosphotyrosine antibodies or immunoprecipitation of whole-cell
      phosphorylated strips of muscle. RESULTS: The tyrosine kinase inhibitor,
      genestein, significantly inhibited the magnitude of contractions induced by
      phorbol ester, endothelin, angiotensin, and serotonin. In addition, genestein
      inhibited the sustained phase of contractions induced by serotonin. Serotonin
      induced vascular smooth muscle contractions were temporally associated with an
      increase in the phosphorylation of MAP kinase. CONCLUSIONS: These data suggest
      that the activation of MAP kinase is associated with sustained vascular smooth
      muscle contractions. Pharmacologic manipulation of MAP kinase activation may lead
      to new approaches to treat pathologic circumstances of increased vasomotor tone
      such as vasospasm.

PMID- 9279324
TI  - Livedo reticularis, rhabdomyolysis, massive intestinal infarction, and death
      after carbon dioxide arteriography.
AB  - In patients with renal insufficiency or hypersensitivity to iodinated contrast
      material, carbon dioxide gas (CO2) is generally considered a safe alternative
      contrast media for digital subtraction angiography. However, we herein report a
      previously undescribed fatal complication of CO2 angiography in a patient with
      acute renal dysfunction and congestive heart failure. The possible pathogenetic
      mechanisms of this complication are discussed.

PMID- 9279326
TI  - Successful controlled limb reperfusion after severe prolonged ischemia.
AB  - Controlled limb reperfusion was performed in two patients who were admitted for
      lower limb-threatening ischemia as a result of embolism. After embolectomy, the
      inflow blood was drained with a cannula and mixed with a crystalloid solution to
      obtain an hyperosmolar, hypocalcemic, alkalotic, and substrate-enriched
      (aspartate, glutamate) reperfusate. This reperfusate was reinjected with a roller
      pump for 30 minutes through two cannulas inserted in the profunda and superficial
      femoral arteries. Temperature, intraarterial pressures, and flow were closely
      controlled. No complications occurred, and complete recovery of motor and sensory
      functions were observed, with restoration of pedal pulses.

PMID- 9279325
TI  - Left atrial myxoma with embolization presenting as an acute infrarenal aortic
      occlusion.
AB  - We present the case of a 42-year-old woman who had acute total infrarenal aortic
      occlusion resulting from embolic implantation from a left atrial myxoma. We
      propose that the small aortic aneurysm that was discovered and repaired in this
      case may be a direct result of invasion and destruction of the aortic elastic
      laminae by implanted myxomatous tissue originating in the primary atrial tumor.
      This behavior has been noted in small vessels of the cerebrum and upper
      extremities with this lesion, but no prior reports of this occurrence in the
      aorta has been noted after extensive review of the literature.

PMID- 9279327
TI  - Secondary rupture of a common iliac artery aneurysm after endovascular exclusion
      and stent-graft infection.

PMID- 9279328
TI  - Regarding "Impact of arterial surgery and balloon angioplasty on amputation: a
      population-based study of 1155 procedures between 1973 and 1992".

PMID- 9279329
TI  - Familial Creutzfeldt-Jakob disease. Codon 200 prion disease in Libyan Jews.
AB  - Creutzfeldt-Jakob disease (CJD) is the most prevalent of the human prion
      diseases, a group of fatal neurodegenerative disorders afflicting both humans and
      animals. The unique characteristic of these diseases, whether sporadic,
      dominantly inherited, or acquired by transmission, is the accumulation in the
      brain of an abnormal isoform (PrPSc) of the cellular prion protein (PrPc).
      Progress has been made in understanding inherited prion diseases by genetically
      linking clusters of familial CJD (fCJD) to mutations of the PrP gene (PRNP). One
      of the largest clusters of fCJD exists among Jews of Libyan origin. The clinical
      and pathologic manifestations of CJD in this community resemble those seen with
      sporadic CJD (sCJD), but the incidence is about 100 times higher than in the
      general population. Initially, this high incidence was attributed to infection
      via consumption of sheep brains or eyeballs, but a mutation at codon 200 in PRNP
      resulting in the substitution of lysine (K) for glutamate (E), designated E200K,
      was identified in this population. The onset of fCJD (E200K) is age dependent and
      shows nearly complete penetrance by age 85 years. fCJD in Libyan Jews is
      invariably associated with accumulation of the pathologic isoform PrPSc in the
      central nervous system. Using mutation-specific antibodies, it was shown that
      most PrPSc in the brain of these patients originated from the mutant protein.
      Some studies suggest that mutant PrP may accumulate in brain and other organs due
      to an impaired degradation, and its accumulation has been postulated to promote
      conversion into PrPSc. fCJD (E200K) has been transmitted to primates and
      transgenic mice, highlighting the need to address ethical and public health
      issues surrounding the possibility of human to human transmission.

PMID- 9279330
TI  - Group A streptococcal bacteremia. A 10-year prospective study.
AB  - In this paper we present a prospective evaluation of 100 patients with Group A
      Streptococcal (GAS) bacteremia evaluated in our hospital over a 10-year period.
      Sixty-two patients were intravenous drug users (IVDU); all but 1 of these had an
      obvious cutaneous portal of entry related to the injection of illicit drugs.
      Twenty-seven patients had infectious metastasis, and the presence of septic
      pulmonary embolism was associated with suppurative phlebitis. Four of these
      patients had endocarditis. In the non-IVDU group, 24 patients had an underlying
      disease, and 12 were immunosuppressed. In 14 cases the infection was of hospital
      acquisition; in 35% infection was related to medical manipulations. Comparing the
      IVDU and non-IVDU groups, GAS bacteremia in IVDU patients is associated with a
      more benign outcome, a longer time of evolution before diagnosis, and a lower
      frequency of septic shock and mortality than in non-IVDU patients. Although in
      the univariate analysis GAS bacteremia was associated with several variables, in
      the multivariate analysis only the presence of shock and nosocomial acquisition
      of the infection were independently associated with a fatal outcome. Fifty-two
      patients were infected with human immunodeficiency virus (HIV); 5 of these were
      in the non-IVDU group. During the last 5 years of study, GAS bacteremia in our
      hospital was 39 times more frequent in HIV-infected patients than in patients
      without HIV. Nine patients presented clinical criteria corresponding to
      Streptococcal toxic shock syndrome (STSS), although its incidence was lower in
      the IVDU group. In the non-IVDU group, STSS was more frequent in patients with a
      necrotizing portal of entry, an age between 20 and 40 years, women, and when the
      origin of the infection was the skin or soft tissue. Six patients with STSS died,
      and death was associated with the presence of necrotizing lesions and lower
      counts of white cells, platelets, or hemoglobin.

PMID- 9279331
TI  - Invasive Aspergillus sinusitis in patients with human immunodeficiency virus
      infection. Report of 2 cases and review.
AB  - Aspergillus sinusitis is an uncommon complication of advanced human
      immunodeficiency virus (HIV) infection. We describe 2 patients with AIDS who
      developed histologically proven invasive Aspergillus sinusitis. We also review
      the findings of 14 histologically documented and 5 probable cases of invasive
      Aspergillus sinusitis. The literature on the prevalence, predisposing factors,
      diagnosis, treatment, and prognosis of the infection is reviewed. Major risk
      factors for the disease are advanced AIDS, chronic sinusitis or otitis,
      neutropenia, use of corticosteroids and prolonged use of broad spectrum
      antibiotics. The most common presenting symptoms are nonspecific and include
      fever, local pain, and swelling. Despite the newer diagnostic and therapeutic
      approaches discussed herein, the infection is usually fatal in HIV-infected
      patients. Early diagnosis and aggressive treatment remain the only available
      means to improve the currently dismal prognosis of Aspergillus sinusitis.

PMID- 9279332
TI  - Deep infections caused by Scedosporium prolificans. A report on 16 cases in Spain
      and a review of the literature. Scedosporium Prolificans Spanish Study Group.
AB  - Scedosporium prolificans, a mold morphologically similar to Scedosporium
      apiospermum, may cause asymptomatic colonization or localized or disseminated
      infection following trauma, surgery, and immunosuppression. S. prolificans is
      normally resistant to available antifungal agents, and prognosis depends largely
      on the host's immune status, extent of infection, and feasibility of surgical
      debridement. We report on 16 patients with deep S. prolificans infections,
      focusing on predisposing factors, clinical characteristics, outcome, postmortem
      findings, and antifungal susceptibility testing to 6 antifungal agents. Between
      1989 and 1994, 16 cases of deep infections by S. prolificans were documented in 6
      clinical centers in Spain (15 adults and 1 child: male/female = 0.77). Fifteen
      patients had underlying hematologic malignancy (14 with neutropenia) and 1 had a
      prosthetic cardiac valve. Syndromes included disseminated infection in 14
      patients (1 with prosthetic valve endocarditis) and fungal pneumonia and
      meningoencephalitis in 1 patient each. S. prolificans was isolated from 2
      specimens in 14 patients and from 1 specimen in 2 patients (blood, n = 12;
      respiratory tract, n = 4; CNS, n = 4; and skin biopsy, n = 3). Antifungal
      susceptibility testing by a micromethod with RPMI-2% glucose medium was performed
      in 8 isolates, all of which were resistant to amphotericin B, flucytosine,
      ketoconazole, fluconazole, itraconazole, and miconazole. All patients received
      antifungal therapy (amphotericin B, n = 9; amphotericin B+ flucytosine, n = 1;
      amphotericin B+ itraconazole, n = 2; liposomal amphotericin B+ itraconazole, n =
      1; amphotericin B+ fluconazole, n = 1 and 2 underwent surgical procedures. Two
      patients survived coinciding with hematologic recovery and 14 (87.5%) patients
      died in a median time of 4 days after the first positive culture (range, 0-60 d).
      Necropsy was performed in 10 patients, and disseminated infection was found in 9.
      In conclusion, S. prolificans is an emerging multiresistant fungal pathogen that
      may cause asymptomatic colonization, localized infection related to trauma or
      surgery, and rapidly fatal disseminated infection in immunocompromised hosts,
      particularly those with neutropenia. This mycosis underscores the urgent need for
      new antifungal agents.

PMID- 9279333
TI  - Long-term effects of bisphosphonates on the growing skeleton. Studies of young
      patients with severe osteoporosis.
AB  - Osteoporosis in children and adolescents is relatively uncommon and usually
      secondary to identifiable causal factors. There are no generally accepted
      therapies for patients with no treatable underlying cause of disease. Any
      treatment of young patients with bone-acting compounds should be not only
      effective but also devoid of adverse effects on bone growth and remodeling. For
      many years we have been studying the effects of bisphosphonates-an effective
      treatment of postmenopausal osteoporosis-on the growing skeleton. We review here
      our experience in the treatment of young patients with osteoporosis with special
      emphasis on issues of skeletal safety and effectiveness, and we discuss the
      available literature data. We studied 12 patients aged between 10.7 and 17.2
      years with symptomatic osteoporosis and multiple fractures treated with the
      bisphosphonates pamidronate or olpadronate for periods between 2 and 8 years
      continuously. Linear growth continued normally on treatment; there was even a
      catch-up growth in prepubertal patients, and there was no excessive suppression
      of bone remodeling, assessed biochemically. Bone biopsies obtained at various
      stages during treatment showed bone of normal lamellar structure without
      mineralization defects. There was an increase in calcium balance, already evident
      within 10 days, the level of which was maintained for at least 3 years of
      treatment. This was associated with progressive increases in bone mineral density
      along a different slope from that of healthy peers as well as correction of
      vertebral deformities on X-rays in patients given bisphosphonates before puberty.
      Treatment was well tolerated and clinical improvement was remarkable. Our
      studies, supported by literature data, strongly suggest that bisphosphonate
      therapy can be beneficial to young patients with osteoporosis for whom no other
      options are currently available, and justify planning controlled studies in more
      common conditions for which no treatment is currently available, such as
      osteogenesis imperfecta.

PMID- 9279334
TI  - Musculoskeletal infections in patients with human immunodeficiency virus
      infection.
AB  - Musculoskeletal infections constitute an unusual clinical manifestation in
      patients with human immunodeficiency virus (HIV) infection. Available information
      about patients' characteristics and their clinical course has been obtained
      mainly from case reports and small retrospective studies. Our retrospective study
      is the largest in the literature providing detailed information about the
      clinical and laboratory characteristics of HIV-infected patients with different
      musculoskeletal infections. We identified 30 patients with various infections of
      the musculoskeletal system during a 5-year period among a cohort of 3,000-4,000
      HIV-infected patients, and we describe them along with all cases of
      musculoskeletal infections in patients with HIV reported in the literature since
      1985. Septic arthritis was the most commonly reported infection of the
      musculoskeletal system. It usually affects young men with a median CD4 count of
      241. The exact contribution of a previous history of intravenous drug abuse in
      the pathogenesis of septic arthritis is unclear from the present and previous
      studies. Staphylococcus aureus was the most commonly isolated agent (31.3%).
      Numerous atypical pathogens were also identified as causes of septic arthritis.
      Approximately 90% of patients recovered with appropriate antibiotic treatment.
      Osteomyelitis was a more serious infection which also affected young individuals
      but with lower CD4 counts (median, 41). Half the cases were due to atypical
      mycobacteria. The mortality rate in the previously reported cases and in our
      series was high (20%). Pyomyositis is an increasingly recognized infection of the
      striated muscles in HIV-infected patients. It affects almost exclusively males
      with advanced HIV infection (median CD4 count, 24). Most cases are due to
      Staphylococcus aureus (67%). Drainage of the involved muscle(s) accompanied by
      proper antibiotic treatment resulted in resolution of the infection in the
      majority of patients (90%). Although the incidence of musculoskeletal infections
      in patients with HIV from this and previous studies appears to be low (0.3%
      3.5%), these infections add a significant morbidity and mortality in the affected
      individuals. Better understanding of their pathogenesis and clinical course would
      aid the proper diagnosis and management of these infections.

PMID- 9279335
TI  - Invasive pneumococcal infections. A comparison between adults and children.
AB  - A similar number of adults and children had invasive pneumococcal infection.
      There was male predominance, and different ethnic distribution between children
      and adults. The majority of adults (78%), had underlying diseases, but this was
      less frequent in children (24%). The presenting illness differed between adults
      and children. Complications of invasive pneumococcal infection occurred more
      frequently in adults than in children. The mortality rate in adults was 21.5%; in
      children, only 3.8%. The rate of penicillin-resistant pneumococci at our hospital
      was 23%, while cefotaxime resistance was 4.2%. Penicillin-resistant pneumococci
      were not isolated more frequently from children than from adults. Patients with
      penicillin-resistant pneumococci had longer duration of hospitalization and more
      nosocomially acquired infections. No difference in the mortality rate was found
      between patients with resistant or sensitive pneumococci. Ninety-five percent of
      strains were included in the current vaccine, but less than 2% of patients had
      been vaccinated. Isolates prevalent in Europe and the United States (19, 5, 1,
      14, 6, 18, 12, 4, 9, 23, 7) were also most prevalent in Jerusalem. The
      distribution of serotypes differed between children and adults, and between
      patients from whom resistant organisms were isolated as opposed to sensitive
      organisms.

PMID- 9279336
TI  - [Chronochemotherapy for cancer].
AB  - The chronomodulation of anticancer drugs arouses our interest as a method for
      cancer chemotherapy. The author reviewed recent clinical studies regarding
      circadian rhythms in 1) target tissues: healthy and cancer tissues; 2)
      chronopharmacology of anticancer drugs; and 3) chronotoxicity of anticancer
      drugs. A brief review is made of the main results of clinical phase II trials.

PMID- 9279337
TI  - [Adjuvant tamoxifen duration: more large-scale randomized evidence is needed].
AB  - The Early Breast Cancer Trialists' Collaborative Group (EBCTCG) overview of
      worldwide evidence has demonstrated that a few years of adjuvant tamoxifen
      produces a moderate but definite benefit in long-term survival. However, there is
      major uncertainty regarding the optimal duration of tamoxifen treatment and in
      particular, as to whether, after a few years on tamoxifen, most women should stop
      or should continue for several years longer. ATLAS (Adjuvant Tamoxifen: Longer
      Against Shorter) is a large international randomized trial designed to assess
      reliably the balance of benefits and risks of prolonging tamoxifen duration by an
      additional five years in women who have already had some years of adjuvant
      tamoxifen and for whom there is uncertainty about whether to stop, or to continue
      for longer. It is important that most of the clinicians are aware of the
      uncertainties regarding the optimal duration of tamoxifen and should consider
      entering their patients into ATLAS, which has the potential to provide reliable
      evidence to answer this question that affects the management of many hundreds of
      thousands of women worldwide and thereby may contribute to the further downward
      trend in breast cancer mortality which is already being seen.

PMID- 9279339
TI  - [Fundamental studies on the surgical adjuvant chemotherapy to support the
      clinical efficacies].
AB  - There have been many evidences for the usefulness of surgical adjuvant therapy of
      human advanced solid malignancies. Experimentally, many studies to support
      efficacies of such adjuvant therapy were reported. In this paper, such studies
      carried out abroard and in Japan were reviewed. Especially, several experimental
      studies in Japan using UFT as the drug used in adjuvant settings were introduced.
      In these reports, UFT was reported as a drug effective experimentally in adjuvant
      treatment. This fact seemed to support the clinical efficacies of UFT in surgical
      adjuvant chemotherapy.

PMID- 9279340
TI  - [Evaluation of clinical trials on adjuvant chemotherapy for curatively resected
      gastric cancer].
AB  - Reports of the results of clinical trials on adjuvant chemotherapy for curatively
      resected gastric cancer in Japan and other countries were reviewed. The efficacy
      of adjuvant chemotherapy outside Japan was not recognized except in two trials.
      Japanese trials did not reveal a significant survival benefit compared with
      surgery alone. However, a consensus was achieved in Japan on its efficacy by
      understanding some results of subset analysis as definite proof. Recently, it has
      been recognized that the re-evaluation of adjuvant chemotherapy should be carried
      out with the control group of surgery alone. The results of the trials of JCOG
      and N.SAS-GC, comparing adjuvant chemotherapy versus surgery alone, are much
      awaited. At the present time, carefully designed randomized controlled trials
      with sufficient sample size, which include surgery alone for control arm, are the
      only way to establish the efficacy of adjuvant chemotherapy.

PMID- 9279342
TI  - [Benefits of adjuvant chemotherapy for breast cancer].
AB  - The main therapy for primary breast cancer is not surgery, but a systemic therapy
      involving administration of cytotoxic chemotherapy or the use of ablative or
      additive endocrine therapy to control disseminated micrometastasis. The results
      of randomized trials and meta-analysis show that CMF, the standard adjuvant
      chemotherapy, is effective regardless of axillar lymph node involvement or
      menopausal status. Effectiveness of adjuvant chemotherapy with an anthracyclin
      based regimen remains controversial. The trial by CUBC and NSAS-BC comparing UFT,
      widely used in the management of patients with breast cancer in Japan, with CMF
      is on-going.

PMID- 9279341
TI  - [The current status of postoperative adjuvant chemotherapy for colorectal
      cancer].
AB  - To evaluate the significance of postoperative adjuvant chemotherapy, randomized
      controlled trials of adjuvant chemotherapy after curative resection for
      colorectal cancer were reviewed. Several multiple-drug systemic chemotherapy
      (MOF, MMC/FT p.o., MMC/5-FU p.o., MMC/ UFT po) were useful as adjuvant treatment
      to improve survival or disease-free survival for patients with colorectal cancer.
      And worldwide meta-analysis found that continuous intraportal 5-FU was suggested
      to improve survival. Recently, combination chemotherapy trials utilizing 5-FU and
      levamisole, or 5-FU and leucovorin, demonstrated significant a survival advantage
      in the patients with high risk colon cancer, and these are widely used as
      adjuvant treatment for patients with Dukes C resected colon cancer. From results
      of many Japanese trials, although the effectiveness of adjuvant treatment for
      colorectal cancer still remain controversial, postoperative adjuvant chemotherapy
      is thought to improve the disease-free survival of patients after resection of
      rectal cancer or Dukes C colon cancer.

PMID- 9279343
TI  - [Adjuvant chemotherapy for non-small cell lung cancer].
AB  - Surgery is the first choice for patients in the early stage of non-small cell
      lung cancer (NSC-LC). But, even for pathologic stage I patients, the post
      operative survival remains unsatisfactory; the five-year survival rate is around
      70 percent, in spite of potential curative resections. Therefore, post-operative
      adjuvant chemotherapy is considered to be necessary to improve the survival.
      Although many prospective randomized studies of post-operative adjuvant
      chemotherapy have been conducted, the efficacy of post-operative chemotherapy for
      NSCLC has not been proved (a consensus report of post-operative adjuvant
      treatment for NSCLC, 3rd IASLC Workshop, Bruges, August 1993). It has been
      recently reported by the West Japan Study Group for Lung Cancer Surgery (WJSG)
      that oral administration of UFT (a mixture of tegafur and uracil) as a post
      operative adjuvant chemotherapy is effective for patients with complete resected
      NSCLC (stage I to III) and that UFT administration is tolerable with mild adverse
      effects in most patients. In order to improve postoperative survival of patients
      with more advanced stage NSCLC (e.g., bulky N2, III b), we has introduced
      biochemical modulation therapy using 5-FU, UFT combined with CDDP.

PMID- 9279344
TI  - [TUT-7 early phase II clinical study for various solid tumors and hematologic
      malignancies].
AB  - An early Phase II study with TUT-7 (menogaril), a new anthracycline antitumor
      antibiotic, was conducted in patients with various malignant tumors at 81
      departments of 65 institutions nationwide. One course of TUT-7 treatment
      consisted of seven (7) or fourteen (14) consecutive days of administration at 75
      or 100 mg/body/day with two-week drug withdrawal; at least two courses of
      treatment were given in principle. Among the 165 patients registered, 145
      patients were eligible and 128 patients were evaluable for antitumor efficacy. In
      11 patients with malignant lymphoma, one (1) had CR and five (5) had PR (54.5%);
      in three (3) patients with prostate cancer, one (1) had PR (33.3%); and in 12
      patients with uterine cervical cancer, two (2) had PR (16.7%). Adverse drug
      reactions frequently observed were digestive organ disorders (anorexia and
      nausea/vomiting) and malaise. The abnormality in laboratory tests observed
      frequently was myelosuppression (leukopenia and neutropenia).

PMID- 9279345
TI  - [Menogaril (TUT-7) late phase II study for malignant lymphoma, adult T-cell
      leukemia and lymphoma (ATLL)].
AB  - A late Phase II multicenter study with menogaril was conducted nationwide in
      patients with malignant lymphoma [non-Hodgkin's lymphoma (NHL), Hodgkin's disease
      (HD)], and ATLL, menogaril was orally administered at 100 mg daily after
      breakfast, for seven consecutive days with two- or three-week drug withdrawal,
      then menogaril administration was repeated. For malignant lymphoma, in 81
      patients with NHL and 5 patients with HD registered, 70 and 5 patients were
      evaluable for efficacy, respectively. The efficacy rates were 32.9% (6 CRs + 17
      PRs/70) for NHL and 20.0% (1 PR/5) for HD, respectively; that for the NHL
      patients with prior anthracycline antibiotic chemotherapy was 30.5% (5 CRs and 13
      PRs/59). For ATLL, among the 16 patients registered, 15 were evaluable for
      efficacy, and the efficacy rate was 40.0% (2 CRs and 4 PRs/15). Adverse drug
      reactions frequently observed in the patients with malignant lymphoma and ATLL
      included bone-marrow suppression and gastrointestinal symptoms such as anorexia,
      and nausea/vomiting. With these results, menogaril was considered to be effective
      for the treatment of non-Hodgkin's lymphoma and ATLL.

PMID- 9279346
TI  - [Evaluation of neo-adjuvant chemotherapy for oral squamous cell carcinoma].
AB  - In the present study, we investigated the clinical and histopathological effects
      of CP therapy consisting of cisplatin (CDDP 50 mg/m2) or carboplatin (CBDCA 300
      mg/m2) and peplomycin (PEP 5 mg/day) for 25 patients with oral squamous cell
      carcinoma. The effects of treatment and associated complications were as follows:
      1) Complete response (CR) was achieved in 8 and partial response (PR) in 14 of
      the 25 cases. The overall clinical response rate was 88%. The histological
      response rate was 64%. 2) The clinical effects were not always consistent with
      the histopathological effects. There were discrepancies between the clinical and
      histopathological effects, especially in PR determined by clinical findings. 3)
      The principal adverse reaction was gastro-intestinal disturbances, but symptoms
      were able to be controlled. Signs of hematologic toxicity and renal disturbance
      were mild and did not preclude the continuance of therapy. The results of this
      study indicated that neo-adjuvant chemotherapy with CDDP and PEP was highly
      effective for the local control of oral squamous cell carcinoma.

PMID- 9279347
TI  - [Efficacy of chemotherapy for clear cell adenocarcinoma of the ovary].
AB  - In line with various protocols for chemotherapy of ovarian carcinoma, we used EP
      (etoposide-cisplatin or carboplatin) therapy in 10 patients with clear cell
      adenocarcinoma as the first line chemotherapy. Four of these cases were in
      advanced stage at IIIc, and had residual tumor after the operation. One of these
      patients with measurable tumor responded to semi-high dose treatment, and 5-days
      of continuous infusion of etoposide resulted in CR. Three cases of a patient at
      the stages of Ic and IIc are in disease free status after two years of standard
      dose EP therapy. Therefore, high-dose EP therapy might be an effective
      chemotherapy for some patients with ovarian clear cell adenocarcinoma.

PMID- 9279348
TI  - [Combination chemotherapy with nedaplatin, bleomycin and ifosfamide for advanced
      cervical cancer of the uterus--a preliminary study for phase III clinical study].
AB  - A preliminary co-operative study by 7 institutes was conducted to determine the
      optimal dosage of the combination regimen with nedaplatin, bleomycin and
      ifosfamide, which is used in a phase III clinical study, to investigate its
      efficacy as neoadjuvant chemotherapy against advanced cervical cancer of the
      uterus. The drug administration consisted of 3 step; in the first step,
      nedaplatin and bleomycin were administered in a single dose at 80 mg/m2 and a 6
      day dose at 7.5 mg/body/day, respectively, and this combination treatment was
      repeated every 4 weeks. After confirming the safety and efficacy of this
      combination regimen, the second-step treatment was started in which a 5-day dose
      of ifosfamide at 600 mg/m2/day was added to the combination regimen of the first
      step. In the third step, this three-drug combination regimen was used with the
      daily dose of ifosfamide increased up to 1,200 mg/m2. The drug administration was
      conducted in a total of 16 cases, consisting of 3 cases in the first step, 7 in
      the second step and 6 in the third step, which were all evaluable for tumor
      response and safety. Regarding tumor response, a 33.3% (1/3) of response rate was
      obtained in the first step, 71.4% (5/7) in the second step and 66.7% (4/6) in the
      third step. As for safety, bone marrow suppression indicated by grade 4 abnormal
      clinical laboratory test values was found in one case each in the second step
      (leukopenia and thrombocytopenia) and the third step (leukopenia). Thus, bone
      marrow suppression, mainly leukopenia and thro mbocytopenia, was regarded as the
      dose limiting factor of this three-drug combination regimen. The leucocyte and
      thrombocyte counts reached their nadirs at two weeks after administration with
      recovery in about two weeks. The other abnormal changes in clinical laboratory
      test values such as those indicating the effects on renal function were slight
      even in the third step. Nausea and vomiting, anorexia and fever were found in
      every step with high incidences. Alopecia was found in all cases of the third
      step. Based on the above results, the dosage of the third step (combination
      regimen with a single dose of nedaplatin at 80 mg/m2, 6-day dose of bleomycin at
      7.5 mg/body/day and 5-day dose of ifosfamide at 1,200 mg/m2/day, repeated every 4
      weeks) was considered to be the optimal dosage in the phase III clinical study
      for advanced cervical cancer of the uterus.

PMID- 9279349
TI  - [Efficacy of combination chemotherapy of cyclophosphamide and 5'-deoxy-5
      fluorouridine in a mammary tumor xenograft model, MX-1].
AB  - Efficacy of long-term combination chemotherapy of cyclophosphamide (CPA) and 5'
      deoxy-5-fluorouridine (5'-DFUR), both of which have been widely used as
      chemotherapeutics against breast cancer patients, was examined in a mammary tumor
      xenograft model, MX-1. 5'-DFUR suppressed the tumor growth over a long period and
      prolonged the survival, although it did not reduce the initial tumor burden, CPA
      induced the disappearance of the tumor burden temporarily. However, CPA became
      inaffective despite continuation of treatment, and induced the recurrence of the
      tumor. The combination of these two drugs dramatically reduced the tumor burden,
      and suppressed the recurrence of the tumor over a long period. The tumor
      recurring during CPA monotherapy was resistant to CPA but susceptible to 5'-DFUR,
      which could be a reason for the long-lasting activity of the combination therapy.
      These results indicate that CPA and 5'-DFUR monotherapies have different modes of
      antitumor activities in the long-term therapy model, and that these drugs in
      combination would have better therapeutic advantage than each drug given
      individually.

PMID- 9279350
TI  - [A nonparametric estimation of survival curve with interval censored data].
AB  - Although survival analysis dealing with right-censored data has enjoyed wide use,
      analysis of data with left-censored and interval censored cases is available only
      to a very limited number of clinical researchers because of the difficulty in
      understanding the concepts and performing the calculations. This paper applies
      Turnbull's self-consistency algorithm, which he applied in his paper on survival
      data with only left-censored cases, for nonparametric estimation of survival
      curve including both left and interval censored data. A difference in the
      estimates of survival rate among different modes of calculation was demonstrated
      using the data from the Hematopoietic Cell Transplantation Registry of the Japan
      Society for Hematopoietic Cell Transplantation, which illustrated the necessity
      of a correct analysis.

PMID- 9279351
TI  - [Combination therapy with 5'-DFUR, MMC and CDDP in patient with far advanced
      gastric cancer: report of a case].
AB  - A 48-year-old man was referred to our hospital for a Borrmann 3 type advanced
      gastric cancer. Endoscopic biopsy disclosed poorly differentiated adenocarcinoma.
      Ultrasonography and CT scan revealed left hydronephrosis. Endoscopic retrograde
      cholangiography detected a stenosis of common bile duct at the hepatic hilum due
      to lymph nodal metastasis, and laparoscopy revealed peritoneal dissemination.
      Because the tumor was diagnosed as not for curative resection, the patient was
      treated by 4 courses of combination therapy with 5'-DFUR, MMC and CDDP. No
      adverse effect of chemotherapy was observed. As a result, lymph nodal metastasis
      and peritoneal dissemination were reduced. Curative intent total gastrectomy was
      performed, together with pancreatico-splenectomy, left hemicolectomy,
      cholecystectomy, and extended lymph nodal dissection. The patient is well and
      alive with no sign of recurrence 2 years after operation.

PMID- 9279352
TI  - [A case of recurrent advanced colon cancer treated with CPT-11 for second-line
      chemotherapy].
AB  - A 59-year old male patient had been operated on for sigmoid colon cancer in July,
      1990. Operative findings were, P0, H0, S1, N (-), Stage I, and histological
      findings were ss, ly 2, v0, n (-). In July 1994, the CEA level elevated, and be
      was diagnoted as having para-aortic LN swelling and stenosis of anastomosis of
      colon. He was admitted for treatment of recurrent colon cancer. Initially, he was
      treated with continuous injection of 5-FU, low-dose CDDP and Leucovorin. His CEA
      level decreased and para-aortic LN diminished in size. But, in December 1995, the
      CEA level and para-aortic LN relapsed. 5-FU, CDDP and Leucovorin were
      administered, but the CEA level became more and more elevated. This regimen was
      not considered responsible for drug resistance. CPT-11 was administered at 60
      mg/week 6 times, and 80 mg/week 3 times. The side effects disappeared, LN sightly
      diminished in size, and the CEA level decreased. Judging by the anticancer effect
      without severe side effect, we found CPT-11 a useful drug for second-line
      chemotherapy.

PMID- 9279353
TI  - [Moderately differentiated adenocarcinoma of the rectum: a case report of
      remarkable response to preoperative administration of FT suppository].
AB  - A 50-year-old man with moderately differentiated adenocarcinoma of the rectum was
      operated upon following preoperative administration of FT suppository. Digital
      examination, colonoscopy, and barium enema showed an elevated lesion with central
      ulcer of the rectum. Microscopically, the biopsy specimen demonstrated moderately
      differentiated adenocarcinoma. FT suppository (1,500 mg/day for 52 days, total 78
      g) was administered on an outpatient basis. Rectal amputation including lymph
      node dissection was performed. The tumor markedly reduced in size and changed
      into a small ulcer in the resected specimen. Microscopically, the tumor
      degenerated and changed into xanthogranulomatous tissue with foamy histiocytes.
      Only two tubules of degenerated adenocarcinoma remained. FT suppository for
      rectal cancer is considered to be safe and effective.

PMID- 9279354
TI  - [A case of a premenopausal woman with advanced breast cancer treated with
      aromatization inhibition in combination with luteinizing hormone-releasing
      hormone agonist].
AB  - A 44-year-old premenopausal woman having local recurrence and pleural and bone
      metastases of breast cancer was treated with aromatization inhibition in
      combination with Luteinizing Hormone-releasing Hormone (LH-RH) agonist. The
      dominant site of metastasis was a painful local lesion invading the chest wall. A
      partial response by reducing the size of the local lesion was attained 3 months
      after initiation of treatment. This result suggested that treatment using
      aromatization inhibition in combination with LH-RH agonist would be effective in
      premenopausal breast cancer. To confirm the effectiveness of this treatment,
      comparative study between aromatization inhibition in combination with LH-RH
      agonist aromatization inhibition alone and anti-estrogen in combination with LH
      RH agonist are needed.

PMID- 9279355
TI  - [A case of breast cancer metastasis to the skin and bone 13 years after, and to
      the brain 17 years after mastectomy].
AB  - A case of breast cancer metastasis to the skin and bone 13 years after, and to
      the brain 17 years after mastectomy in a 54-year-old woman, is reported. In 1978,
      the patient, who was then 37 years old, underwent standard radical mastectomy for
      left breast cancer. In 1991, because of skin and bone metastasis, systemic
      chemotherapy with cyclophosphamide, epirubicin, and 5-fluorouracil (CAF) was
      performed, and she partially responded to CAF therapy. In April 1995, the patient
      was admitted for pain of left hip joint and left knee joint. Computed tomography
      of the head revealed a bleeding tumor with marked peritumoral edema. Serum levels
      of carcinoembryonic antigen (250 ng/ml) and CA 15-3 (810 U/ml) were increased.
      Bone metastases were found elsewhere in the body. Again, systemic chemotherapy
      with CAF was performed. CAF chemotherapy stopped the brain metastasis bleeding.

PMID- 9279356
TI  - [Complete tumor regression obtained by chemoendocrine therapy including
      toremifene in two cases of pulmonary metastasis of breast cancer with a history
      of tamoxifen treatment].
AB  - Two cases of recurrent breast cancer, for which combined therapy using toremifene
      and oral chemotherapeutic agents were effective, are reported. In case 1, high
      dose toremifene (120 mg/day) and 5'-DFUR were administered to a forty-seven-year
      old woman with lung metastasis of estrogen-receptor positive breast cancer, who
      had been previously treated with polychemotherapy and tamoxifen. A complete
      response was obtained after six months of treatment and this condition has
      remained for longer than one year. In case 2, a fifty-year-old woman developed
      liver and lung matastasis of breast cancer with increased tumor marker levels.
      Forty mg/day of toremifene and oral cyclophosphamide was started and
      transarterial embolization of the hepatic artery using lipiodol, adriamycin and
      mitomycin C was performed. Both hepatic and pulmonary metastasis disappeared, and
      the tumor maker level was normalized one month later. No regrowth of the tumors
      has been observed for more than six months. The chemosensitizing effect of
      toremifene might be responsible for the favorable effects on these matastases of
      breast cancer.

PMID- 9279358
TI  - [Effects of TNM extension and histopathological type of the tumor on long-term
      survival rates of parotid and submandibular gland cancer].
AB  - The effects of TNM extension and histopathological type of the tumor on 5 and 10
      year survival rates were analysed in 1,147 cases of parotid cancer and 271 cases
      of submandibular gland cancer which had been registered from 152 institutes
      throughout Japan since 1978. Advance of stage decreased the prognosis
      significantly, and the decrease was more pronounced in submandibular gland
      cancer. Facial paralysis also decreased the prognosis of parotid cancer
      significantly. The prognosis was also affected significantly by the
      histopathological type of the tumor. The 5-year survival rates of adenocarcinoma,
      epidermoid carcinoma and undifferentiated carcinoma were only about 30% in
      parotid cancer and about 20% in submandibular gland cancer. In treatment of
      salivary gland cancer, the therapeutic approach should be individualized in
      accordance with the tumor extension and its histopathological type. Improvement
      of accuracy in preoperative diagnosis of salivary gland cancer is of the utmost
      importance.

PMID- 9279357
TI  - [A case of solitary metastatic splenic tumor of ovarian carcinoma].
AB  - The case was a 67-year-old female. In March, 1993, bilateral oophrectomy + total
      hysterectomy+omentectomy were done, for stage III ovarian cancer with peritoneal
      dissemination, and high CA 125 level (2100 U/ml). As postoperative chemotherapy,
      intraperitoneal injection of CDDP 150 mg (4 courses), and intravenous injection
      of CAP (CPA 500 mg/ m2 + epirubicin 25 mg/m2 + CDDP 50 mg/m2) (10 courses) were
      undertaken. In March, 1995, in abdominal CT scan, a solitary splenic tumor was
      found and the tumor marker (CA 125) was again elevated, and splenic metastasis
      was suspected. In June, 1995, intravenous injection of CDDP 70 mg/m2 + CPT-11 60
      mg/m2 (1 course) was given, and the splenic tumor enlarged gradually. In
      February, 1996, a splenectomy was done. In pathological findings, the tumor
      proved to be poorly-differentiated adenocarcinoma the same as primary ovarian
      cancer, and after splenectomy, CA 125 fell below the normal value. The diagnosis
      was solitary splenic metastasis from ovarian carcinoma.

PMID- 9279359
TI  - Bcl-2 and c-myc expression, cell cycle kinetics and apoptosis during the
      progression of chronic myelogenous leukemia from diagnosis to blastic phase.
AB  - Chronic myelogenous leukemia (CML) has a progressive course but little is known
      about the biologic characteristics of disease progression. This study was
      designed to assess the changes in cell proliferative characteristics, apoptosis,
      the expression of the bcl-2 and c-myc genes between the time of initial diagnosis
      and entrance into the blastic phase of the disease. We observed that the rate of
      cell proliferation decreased and the cell death rate did not significantly change
      as the disease accelerated. The level of bcl-2 expression was significantly
      higher in accelerated/blastic phase cells than in the chronic phase cells in the
      population as a whole, however, the bcl-2 expression level did not change in
      blast cell subpopulation. c-myc Expression was significantly higher in the blast
      cell subpopulation of accelerated/blastic phase than in that of earlier phases of
      the disease. In conclusion, the characteristics of CML cells, namely
      proliferation rate, c-myc and bcl-2 change during the course of the disease. It
      is possible that the change in c-myc expression plays a causative role in
      evolution of the blastic phase from the chronic phase.

PMID- 9279360
TI  - Multiple centrosomal microtubule organising centres and increased microtubule
      stability are early features of VP-16-induced apoptosis in CCRF-CEM cells.
AB  - Microtubular reorganisation contributing to apoptotic morphology occurs in normal
      and neoplastic cells undergoing apoptosis induced by cytotoxic drugs [1-3]. The
      aim of this study was to correlate the changes in the microtubules (MTs) with
      behavior of the centrosome in apoptotic cells, and to see whether post
      translational changes in tubulin occurred with the emergence of apoptotic MT
      bands. Apoptosis was induced in the human T-cell leukaemia line (CCRF-CEM) by
      treatment with 17 microM etoposide over a 4 h period. The time course of changes
      was assessed using flow cytometry (FCM) and immunocytochemistry in cells labelled
      for a centrosomal antigen (CSP-alpha) or alpha-tubulins. One hour following
      treatment we observed multiple centrosomal microtubule organising centres (MTOCs)
      associated with the nucleus and the transient appearance of a subset of stable
      MTs detected with an antibody specific for acetylated alpha-tubulin, as the bands
      of MTs which lobulate the nucleus are formed. The altered properties of the MTs
      thus reflect changes in function as apoptosis progresses.

PMID- 9279361
TI  - The isolation of a DNA synthesome from human leukemia cells.
AB  - In this report we describe, for the first time, the purification and
      characterization of a replication-competent multiprotein form of DNA polymerase
      (designated the DNA synthesome) from the human leukemia cell line (HL-60) using a
      series of centrifugation, ion-exchange chromatography and velocity sedimentation
      steps. The proteins and enzymatic activities thus far identified to co-purify
      with the leukemia cell DNA synthesome include the DNA polymerases alpha and
      delta, DNA primase, proliferating cell nuclear antigen (PCNA), replication factor
      C (RF-C), replication protein A (RP-A), and DNA topoisomerases I and II. We have
      demonstrated that the DNA synthesome is fully competent to replicate simian virus
      40 (SV40) replication origin containing DNA in vitro in the presence of the viral
      large T-antigen. This result implies that all of the cellular activities required
      for large T-antigen-dependent in vitro SV40 DNA synthesis are present in the
      isolated human leukemia cell DNA synthesome. Since SV40 is extensively dependent
      on the host cell's DNA synthetic machinery for its own DNA replication, our
      results indicate that the isolated leukemia cell DNA synthesome may play a role
      not only in viral DNA synthesis but also in human leukemia cell DNA replication.
      We recently proposed a model to represent the DNA synthesome that was isolated
      from HeLa and murine cells. Our data indicate that the organization of the DNA
      synthesome from HL-60 cells also fits this proposed model. The purified DNA
      synthesome will not only allow the further study of the molecular mechanisms
      required to carry out human leukemia cell DNA replication, but may also provide a
      tool for eventually dissecting some of the regulatory controls of the cell's DNA
      synthetic machinery.

PMID- 9279362
TI  - Actin polymerization in neutrophils from patients affected by myelodysplastic
      syndromes--a flow cytometric study.
AB  - In this study F-actin polymerization in neutrophils from 21 patients affected by
      myelodysplastic syndromes (MDS) was evaluated by means of a flow cytometric
      assay. Neutrophils were stimulated with formyl-methionyl-leucyl-phenylanaline
      (fMLP; 10(-8) M final concentration) for 15, 30, 60 and 120 sec, and F-actin
      content was determined using fluorescein-isothiocyanate phallacidin as a specific
      probe. Eight normal subjects were studied as controls. We found that F-actin
      polymerization was defective in ten patients, with very impaired values after 60
      and 120 sec of stimulation with fMLP. The remaining 11 patients showed a
      prevalent neutrophil population with normal F-actin polymerization and neutrophil
      sub-populations with either defective or undetectable F-actin polymerization. In
      the first group, patients with very poor prognosis (refractory anemia with excess
      blasts, refractory anemia with excess blasts in leukemic transformation, trisomy
      8, multiple karyotypic abnormalities) were present, although patients with
      aberrations of karyotype were present in the second group. It is possible that
      defects in neutrophil F-actin polymerization may be responsible for neutrophil
      dysfunction, which has frequently been observed in MDS.

PMID- 9279363
TI  - Suppressed formation of bone marrow adherent layers derived from acute myeloid
      leukemia patients after in vitro exposure to interleukin-4.
AB  - Long-term bone marrow cultures from ten acute myeloid leukemia (AML) patients
      exposed to recombinant human (rhu) interleukin (IL) 4 from culture initiation
      failed to develop adherent layers at 5 weeks as compared to controls. The
      adherent layers from two of our patients expressed IL-1 beta transcripts
      constitutively, and all produced IL-6 and leukemia inhibitory factor (LIF)
      proteins. Our results demonstrate that rhuIL-4 markedly inhibited AML-derived
      adherent layer formation in a time- and dose-dependent manner, and this effect
      was not mediated through enhanced apoptosis and did not correlate with IL-1 beta,
      IL-6 or LIF production.

PMID- 9279364
TI  - Effects of retinoic acid on a new human erythromegakaryocytic cell line AP-217.
AB  - We have characterized a new human cell line AP-217, derived from the peripheral
      blood of a patient with chronic myeloid leukemia in blastic crisis. The analysis
      of cell surface antigens and ploidy showed that AP-217 was an erythro
      megakaryocytic cell line. The effects of inducers of differentiation were studied
      and focused on retinoic acid (RA). Uninduced AP-217 cells produced a low level of
      hemoglobin (Hb) that showed a moderate but significant dose-dependent increase
      after 13 cis-RA induction (four times above the control at 10(-5) M). To outline
      this effect, AP-217 cells were cloned at limiting dilution. A subclone (clone 2)
      was isolated which expressed glycophorin A on 12% of cells, and showed a marked
      sensitivity to RA. After a 4 day induction with increasing concentrations of RA
      (1-10 x 10(-6) M) Hb production by clone 2 cells was enhanced 12 times over the
      control at the highest concentration (10(-5) M). No effect of RA on the Hb
      production of K-562 and HEL was observed. This increased Hb production occurred
      simultaneously with a growth inhibition in clonogenic cultures (20% reduction)
      associated with a drastic reduction of the colony size. Moreover, we demonstrated
      the expression of mRNA for the beta globin gene in clone 2 and AP-217-cells. This
      is the first report of a positive effect of RA on the erythroid differentiation
      of a human leukemic cell line.

PMID- 9279365
TI  - Induction of macrophage colony-stimulating factor receptor up-regulation in THP-1
      human leukemia cells is dependent on the activation of c-fyn protein tyrosine
      kinase.
AB  - We investigated the role of fyn kinase on the expression of macrophage colony
      stimulating factor (M-CSF) receptors (M-CSFR) and macrophage differentiation
      using a human myelomonocytic leukemic cell line THP-1. Treatment of THP-1 cells
      with Bryostatin 1 (bryo 1), a potent protein kinase C (PKC) activator, caused a
      major fraction of them to become adherent (AD) with distinct monocyte/macrophage
      characteristics. The differentiation was associated with an enhanced expression
      of M-CSFR and fyn tyrosine kinase activity, occurring primarily on cells in the
      AD fraction. Scatchard plot analysis showed that the enhanced expression of M
      CSFR binding activity was due to an increase in total receptor number per AD
      cell, rather than an increase in the binding affinity. Fyn antisense (AS)
      phosphorothioate oligonucleotides (s-oligos) inhibited the up-regulation of both
      M-CSFR and c-fms transcripts in bryo 1-treated THP-1 cells. In contrast, fyn
      sense s-oligos did not affect the up-regulation of either M-CSFR or c-fms mRNA in
      bryo 1-treated cells. In addition, fyn AS s-oligos blocked the expression of AD
      capacity in bryo 1-treated THP-1 cells. The efficacy of fyn AS s-oligos as
      macromolecular inhibitors was verified by their ability to lower fyn-associated
      tyrosine kinase and in vitro autophosphorylation activity in bryo 1-treated THP-1
      cells. Taken together, our results show a strong correlation between M-CSFR
      expression and monocytic differentiation in THP-1 cells, and suggest a possible
      role of c-fyn tyrosine kinase in mediating these processes.

PMID- 9279367
TI  - The non-random distribution of point mutations in leukaemia and myelodysplasia--a
      possible pointer to their aetiology.
AB  - A conventional and a computer search of the literature yielded 627 sequenced
      point mutations in the ras and p53 genes in 575 patients with leukaemia and
      myelodysplasia (MDS) out of a total of 4214 investigated. ras Mutations
      predominated in myeloid leukaemia and were more common in the disease in relapse
      than at presentation. There was no clinical, or haematological difference or
      difference in survival between ras positive and ras negative patients with acute
      myeloid leukaemia (AML) in adults or children, but ras mutations carried a poorer
      prognosis in childhood acute lymphocytic leukaemia and an increased risk of
      leukaemia in MDS. p53 mutations predominated in lymphoid leukaemia and were
      several fold more frequent in leukaemia in relapse than in the de novo disease,
      were associated with loss of the normal p53 allele (monosomy 17) in > 50% of
      cases and carried a poor prognosis in AML, MDS and chronic lymphatic leukaemia
      and a 3.8-fold increase risk of death in T cell acute lymphocytic leukaemia.
      There were 163 transitions for every 100 transversions, the expected number being
      ca 50. Consideration of the molecular mechanisms by which nitrous acid produces
      transitions allows transitions resulting from the deamination of cytosine to be
      distinguished from those resulting from the deamination of adenine. The former
      constitute 84.67% and the latter 15.33% of the 372 transitions present. Again
      purine-->pyrimidine and pyrimidine-->purine transversions form 80.35 and 19.65%,
      respectively, of the 228 transversions present. The possible bearing of this
      highly non-random distribution on the aetiology of point mutations in leukaemia
      and myelodysplasia is discussed.

PMID- 9279366
TI  - Shortened survival after relapse in T-cell acute lymphoblastic leukemia patients
      with p16/p15 deletions.
AB  - p16 Alterations were detected in > 60% of 103 primary T-ALL samples. In paired
      diagnosis-relapse patient samples, 80% of the relapse samples with p16 deletion
      were deleted at diagnosis. When p16 was homozygously deleted, p15 gene
      alterations were found in 72% of the diagnosis T-ALL patient samples, increasing
      significantly to 100% at relapse. Alterations of p18 were not detected. No
      clinical significance of p15/p16 gene deletion in diagnosis T-ALL was found with
      respect to white blood cell (WBC) count, incidence of mediastinal mass, rate of
      relapse, duration of first remission or event-free survival. In relapse T-ALL,
      however, patients with p16 deletion experienced a significantly shorter duration
      of post-relapse survival, demonstrating that p16 deletion is clinically
      significant in T-ALL.

PMID- 9279368
TI  - A microgranular variant of acute promyelocytic leukemia with atypical morpho
      cytochemical features and an early myeloid immunophenotype.
AB  - This report describes a unique case of acute promyelocytic leukemia (APL) showing
      elusive morphologic features, an atypical pattern of cytochemical reactions, and
      a previously unreported immunophenotype consistent with a very early myeloid
      form: CD13 (+), CD33 (+), CD9 (+), CD2 (+), HLA-DR (-), CD34 (+), CD117 (+), and
      TdT (+). The diagnosis of AML M3 variant was made only after genotypic analyses
      revealed the PML/RAR alpha rearrangement associated with the typical (15;17)
      (q22;q21) translocation. This example of 'asynchronous differentiation'
      emphasizes the need for a multiparameter approach to the diagnosis of acute
      leukemia.

PMID- 9279369
TI  - Routine fluorescence in situ hybridization analysis for detection of BCR-ABL
      rearrangement in myeloproliferative disorders.

PMID- 9279370
TI  - The Interdependence of Tumor Biology and Clinical Oncology. The 24th meeting of
      the International Society for Oncodevelopment Biology and Medicine. San Diego,
      California, November 17-22, 1996. Abstracts.

PMID- 9279371
TI  - The Chinese hamster Alu-equivalent sequence: a conserved highly repetitious,
      interspersed deoxyribonucleic acid sequence in mammals has a structure suggestive
      of a transposable element.
AB  - A consensus sequence has been determined for a major interspersed
      deoxyribonucleic acid repeat in the genome of Chinese hamster ovary cells (CHO
      cells). This sequence is extensively homologous to (i) the human Alu sequence (P.
      L. Deininger et al., J. Mol. Biol., in press), (ii) the mouse B1 interspersed
      repetitious sequence (Krayev et al., Nucleic Acids Res. 8:1201-1215, 1980) (iii)
      an interspersed repetitious sequence from African green monkey deoxyribonucleic
      acid (Dhruva et al., Proc. Natl. Acad. Sci. U.S.A. 77:4514-4518, 1980) and (iv)
      the CHO and mouse 4.5S ribonucleic acid (this report; F. Harada and N. Kato,
      Nucleic Acids Res. 8:1273-1285, 1980). Because the CHO consensus sequence shows
      significant homology to the human Alu sequence it is termed the CHO Alu
      equivalent sequence. A conserved structure surrounding CHO Alu-equivalent family
      members can be recognized. It is similar to that surrounding the human Alu and
      the mouse B1 sequences, and is represented as follows: direct repeat-CHO-Alu-A
      rich sequence-direct repeat. A composite interspersed repetitious sequence has
      been identified. Its structure is represented as follows: direct repeat-residue
      47 to 107 of CHO-Alu-non-Alu repetitious sequence-A-rich sequence-direct repeat.
      Because the Alu flanking sequences resemble those that flank known transposable
      elements, we think it likely that the Alu sequence dispersed throughout the
      mammalian genome by transposition.

PMID- 9279372
TI  - Biological role of the general control of amino acid biosynthesis in
      Saccharomyces cerevisiae.
AB  - The biological role of the "general control of amino acid biosynthesis" has been
      investigated by analyzing growth and enzyme levels in wild-type, bradytrophic,
      and nonderepressing mutant strains of Saccharomyces cerevisiae. Amino acid
      limitation was achieved by using either bradytrophic mutations or external amino
      acid imbalance. In the wild-type strain noncoordinate derepression of enzymes
      subject to the general control has been found. Derepressing factors were in the
      order of 2 to 4 in bradytrophic mutant strains grown under limiting conditions
      and only in the order of 1.5 to 2 under the influence of external amino acid
      imbalance. Nonderepressing mutations led to slower growth rates under conditions
      of amino acid limitation, and no derepression of enzymes under the general
      control was observed. The amino acid pools were found to be very similar in the
      wild type and in nonderepressing mutant strains under all conditions tested. Our
      results indicate that the general control affects all branched amino acid
      biosynthetic pathways, namely, those of the aromatic amino acids and the
      aspartate family, the pathways for the basic amino acids lysine, histidine, and
      arginine, and also the pathways of serine and valine biosyntheses.

PMID- 9279373
TI  - Cell cycle parameters of Chinese hamster ovary cells during exponential,
      polyamine-limited growth.
AB  - We have previously shown that Chinese hamster ovary cells made polyamine
      deficient by treatment with alpha-methylornithine, an inhibitor of ornithine
      decarboxylase, grow exponentially in culture at low densities at one-half the
      rate observed in untreated (control) cultures. In this study, the cell cycle of
      polyamine-limited cells was examined by using thymidine autoradiography, mitotic
      index analysis, and fraction labeled mitoses analysis. We found that the longer
      doubling time of inhibitor-treated cultures was a consequence of increases in the
      lengths of the G1 and S phases. The expansion of the S phase was proportional to
      the increase in doubling time (twofold), whereas the G1 phase was lengthened by
      slightly more than a factor of 2. The lengths of the G2 and M phases were
      essentially unchanged. Putrescine stimulated the growth of inhibitor-treated
      cultures and restored the cell cycle parameters to those of untreated cells.

PMID- 9279374
TI  - Deoxyribonucleic acid methylation and chromatin organization in Tetrahymena
      thermophila.
AB  - Deoxyribonucleic acid (DNA) of the transcriptionally active macronucleus of
      Tetrahymena thermophila is methylated at the N6 position of adenine to produce
      methyladenine (MeAde); approximately 1 in every 125 adenine residues (0.8 mol%)
      is methylated. Transcriptionally inert micronuclear DNA is not methylated (< or =
      0.01 mol% MeAde; M. A. Gorovsky, S. Hattman, and G. L. Pleger, J. Cell Biol.
      56:697-701, 1973). There is no detectable cytosine methylation in macronuclei in
      Tetrahymena DNA (< or = 0.01 mol% 5-methylcytosine). MeAde-containing DNA
      sequences in macronuclei are preferentially digested by both staphylococcal
      nuclease and pancreatic deoxyribonuclease I. In contrast, there is no
      preferential release of MeAde during digestion of purified DNA. These results
      indicate that MeAde residues are predominantly located in "linker DNA" and
      perhaps have a function in transcription. Pulse-chase studies showed that labeled
      MeAde remains preferentially in linker DNA during subsequent rounds of DNA
      replication; i.e., there is little, if any, movement of nucleosomes during
      chromatin replication. This implies that nucleosomes may be phased with respect
      to DNA sequence.

PMID- 9279375
TI  - Organization and expression of multiple actin genes in the sea urchin.
AB  - A set of at least 11 actin genes has been isolated from genomic recombinant
      deoxyribonucleic acid libraries of the sea urchin Strongylocentrotus purpuratus.
      Most of the isolates derive from a library which represents the genome of a
      single animal. There are at least five distinct types of sea urchin actin gene,
      some of which are represented by multiple copies in the genome. The actin gene
      types are distinguished by nonhomologous flanking sequences and intervening
      sequences, though the protein coding sequences appear in most cases to be quite
      similar. Eight of the 11 genes isolated have been recovered in lambda
      recombinants that contain two actin genes, linked at 5- to 9-kilobase distances.
      Restriction map overlaps suggest that the genome contains an array of at least
      three of these genes spaced over about 30 kilobases of deoxyribonucleic acid. In
      the linkage patterns observed, actin genes of diverse types were linked to each
      other. In early embryos, actin messenger ribonucleic acid (RNA) transcripts of
      1.8 and 2.2 kilobases were found, and the longer of these transcripts was more
      prevalent in the maternal RNA of the egg. From RNA gel blot experiments, we
      conclude that the two transcripts derive from different actin gene types.
      Different repetitive sequences were located to either side of most of the actin
      genes, and in most observed cases the repeat sequences which were adjacent to
      actin genes of a given type were similar. The repeat sequences flanking the actin
      genes belonged to families which were transcribed, but those repeats in the
      neighborhood of the actin genes which have been investigated were not themselves
      represented in the stable RNAs of eggs or early embryos.

PMID- 9279376
TI  - Transcriptional regulation of the Kluyveromyces lactis beta-galactosidase gene.
AB  - We examined the molecular basis for beta-D-galactosidase (EC 3.2.1.23) induction
      in the yeast Kluyveromyces lactis. The protein synthesis inhibitor anisomycin
      effectively blocked both protein synthesis and enzyme induction by lactose.
      Further, hybridization analysis with the cloned beta-galactosidase gene indicated
      coordinate increases in the concentration of beta-galactosidase messenger
      ribonucleic acid and enzyme activity. The half-life of beta-galactosidase
      messenger ribonucleic acid was the same (4.8 +/- 0.4 min) when measured both
      before and at succeeding times during enzyme induction. These results strongly
      support the hypothesis that expression of the yeast beta-galactosidase gene is
      subject to transcriptional regulation.

PMID- 9279377
TI  - Transcription of adenovirus type 2 genes in a cell-free system: apparent
      heterogeneity of initiation at some promoters.
AB  - We examined the transcription of a variety of adenovirus type 2 genes in a cell
      free system containing purified ribonucleic acid polymerase II and a crude
      extract from cultured human cells. The early EIA, EIB, EIII, and EIV genes and
      the intermediate polypeptide IX gene, all of which contain a recognizable TATAA
      sequence upstream from the cap site, were actively transcribed in vitro, albeit
      with apparently different efficiencies, whereas the early EII (map position 74.9)
      and IVa2 genes, both of which lack a TATAA sequence, were not actively
      transcribed. A reverse transcriptase-primer extension analysis showed that the 5'
      ends of the in vitro transcripts were identical to those of the corresponding in
      vivo ribonucleic acids and that, in those instances where initiation was
      heterogeneous in vivo, a similar kind of heterogeneity was observed in the cell
      free system. Transcription of the polypeptide IX gene indicated that this
      transcript was not terminated at, or processed to, the polyadenylic acid addition
      site in vitro. We also failed to observe, using the in vitro system, any
      indication of transcriptional regulation based on the use of adenovirus type 2
      infected cell extracts.

PMID- 9279378
TI  - Sensitivity of a mutator gene in Chinese hamster ovary cell to deoxynucleoside
      triphosphate pool alterations.
AB  - The Thy- mutants of Chinese hamster ovary cells have a 5- to 10-fold elevated
      pool of deoxycytidine 5'-triphosphate (dCTP) and are auxotrophic for thymidine as
      an apparent consequence of a single mutation. thy is also a mutator gene,
      elevating the spontaneous rate of mutation 5- to 200-fold for at least two
      genetic markers. Previous experiments suggested that this mutator activity was
      caused by the elevated pool of dCTP in Thy- cells. To test this, the dCTP and
      deoxythymidine 5'-triphosphate (dTTP) pools were manipulated by altering the
      external concentration of thymidine in the growth medium. The rate of mutation at
      one genetic locus, ouabain resistance, was directly related to cellular dCTP
      content. At the highest level of dCTP the rate in one Thy- strain was
      approximately 200 times that of wild-type cells. However, the relationship
      between dCTP content and the rate of mutation at the ouabain locus was different
      for two mutator strains and wild-type cells. The rate of mutation at a second
      locus, thioguanine resistance, was increased approximately 10-fold over wild type
      regardless of the dCTP-dTTP pools. These experiments suggest that the mutator
      activity of thy is clearly related to dCTP content, but the dCTP level alone does
      not appear to be the cause of the mutator.

PMID- 9279379
TI  - Monocistronic transcription is the physiological mechanism of sea urchin
      embryonic histone gene expression.
AB  - We have examined histone gene expression during the early stages of sea urchin
      embryogenesis. The five histone genes expressed at that time are contained in
      tandem repetitive segments. It has been suggested that adjacent coding regions
      and their intervening spacer sequences are transcribed into large polycistronic
      messenger ribonucleic acid (RNA) precursors. We have subcloned into pBR322
      deoxyribonucleic acid (DNA) sequences mapping either in the coding region, the 5'
      spacer, or the 3' spacer of the H2B histone gene. These clones were used to
      produce radioiodinated hybridization probes. We measured the steady-state
      quantity of H2B messenger RNA as well as spacer-specific RNA in the total RNA
      from embryos taken at various stages of development from fertilization to
      hatching of blastulae (0 to 22 h post-fertilization). Small amounts of RNA
      hybridizing to both spacer probes could be found. However, we show that these
      RNAs form mismatched hybrids with the spacer DNA and therefore cannot originate
      from the spacers present in the histone genes. We conclude that there is no
      detectable transcription of the spacer regions on either side of the H2B histone
      gene. The detection limit for RNA complementary to the 5' spacer sequence
      corresponds to a maximum of about three RNA molecules per cell, an amount shown
      to be far less than the projected steady-state pool size of a putative
      polycistronic transcript, if such a precursor were to be the obligatory
      transcript of the histone genes. (This conclusion was derived by using the known
      rates of production of H2B mRNA throughout early development [R. E. Maxson and F.
      H. Wilt, Dev. Biol., in press].) The physiologically relevant transcript of the
      histone genes in early development is therefore monocistronic and probably
      identical to the messenger RNA itself.

PMID- 9279380
TI  - Yeast L double-stranded ribonucleic acid is synthesized during the G1 phase but
      not the S phase of the cell cycle.
AB  - The cytoplasm of Saccharomyces cerevisiae contains two major classes of protein
      encapsulated double-stranded ribonucleic acids (dsRNA's), L and M. Replication of
      L and M dsRNA's was examined in cells arrested in the G1 phase by either alpha
      factor, a yeast mating pheromone, or the restrictive temperature for a cell cycle
      mutant (cdc7). [3H]uracil was added during the arrest periods to cells prelabeled
      with [14C]uracil, and replication was monitored by determining the ratio of
      3H/14C for purified dsRNA's. Like mitochondrial deoxyribonucleic acid, both L and
      M dsRNA's were synthesized in the G1 arrested cells. The replication of L dsRNA
      was also examined during the S phase, using cells synchronized in two different
      ways. Cells containing the cdc7 mutation, treated sequentially with alpha-factor
      and then the restrictive temperature, enter a synchronous S phase when
      transferred to permissive temperature. When cells entered the S phase, synthesis
      of L dsRNA ceased, and little or no synthesis was detected throughout the S
      phase. Synthesis of L dsRNA was also observed in G1 phase cells isolated from
      asynchronous cultures by velocity centrifugation. Again, synthesis ceased when
      cells entered the S phase. These results indicate that L dsRNA replication is
      under cell cycle control. The control differs from that of mitochondrial
      deoxyribonucleic acid, which replicates in all phases of the cell cycle, and from
      that of 2-micron DNA, a multiple-copy plasmid whose replication is confined to
      the S phase.

PMID- 9279381
TI  - Participation of deoxyribonucleic acid polymerase alpha in amplification of
      ribosomal deoxyribonucleic acid in Xenopus laevis.
AB  - Aphidicolin, a known inhibitor of eucaryotic deoxyribonucleic acid (DNA)
      polymerase alpha, efficiently inhibited amplification of ribosomal DNA during
      oogenesis in Xenopus laevis. DNA polymerase alpha, but not DNA polymerase gamma,
      as isolated from ovaries, was sensitive to aphidicolin. DNA polymerase beta was
      not detectable in Xenopus ovary extracts. Therefore, DNA polymerase alpha plays a
      major role in ribosomal ribonucleic acid gene amplification.

PMID- 9279382
TI  - Selection of specific wheat germ agglutinin-resistant (WgaR) phenotypes from
      Chinese hamster ovary cell populations containing numerous lecR genotypes.
AB  - Three distinct Chinese hamster ovary mutants selected for resistance to wheat
      germ agglutinin were previously described by this laboratory. In this paper,
      evidence is provided that each phenotype occurs at a similar frequency in an
      unmutagenized population of Chinese hamster ovary cells. Two novel wheat germ
      agglutinin resistance phenotypes (WgaR), which also appear to occur at similar
      frequencies were uncovered in the course of these studies. One mutant type
      belongs to a new, recessive complementation group (VIII), and the second belongs
      to a previously defined complementation group (VI). Mutants from each of the four
      WgaR complementation groups (I, II, III, and VIII) exhibited characteristic and
      unique patterns of resistance to the toxicity of a variety of plant lectins.
      These properties were used in developing independent selection protocols which
      were highly specific for the isolation of each of the mutant types.

PMID- 9279383
TI  - Assignment of the chloramphenicol resistance gene to mitochondrial
      deoxyribonucleic acid and analysis of its expression in cultured human cells.
AB  - The mitochondrial deoxyribonucleic acids (mtDNA's) from human HeLa and HT1080
      cells differed in their restriction endonuclease cleavage patterns for HaeII,
      HaeIII, and HhaI. HaeII digestion yielded a 9-kilobase fragment in HT1080, which
      was replaced by 4.5-, 2.4-, and 2.1-kilobase fragments in HeLa. HaeIII and HhaI
      yielded distinctive 1.35- and 0.68-kilobase HeLa fragments. These restriction
      endonuclease polymorphisms were used as mtDNA markers in HeLa-HT1080 cybrid and
      hybrid crosses involving the cytoplasmic chloramphenicol resistance mutation was
      used. mtDNA's were purified and digested with the restriction endonucleases, the
      fragments were separated on agarose gels, and the bands were detected by ethidium
      bromide staining and Southern transfer analysis. Three cybrids and four hybrids
      (four expressing HeLa and three expressing HT1080 chloramphenicol resistance)
      contained 2- to 10-fold excesses of the mtDNA of the chloramphenicol-resistant
      parent. One cybrid, which was permitted to segregate chloramphenicol resistance
      and was then rechallenged with chloramphenicol, had approximately equal
      proportions of the two mtDNA's. Only one hybrid was discordant. These results
      indicated that chloramphenicol resistance is encoded in mtDNA and that expression
      of chloramphenicol resistance is related to the ratio of chloramphenicol
      resistant and -sensitive genomes within cells.

PMID- 9279384
TI  - Actin gene expression in developing sea urchin embryos.
AB  - We show that the synthesis of actin is regulated developmentally during early sea
      urchin embryogenesis and that the level of synthesis of this protein parallels
      the steady-state amounts of the actin messenger ribonucleic acids (RNA). An in
      vitro translation and RNA blotting analysis of embryo RNA from several stages of
      early development indicated that during the first 8 h after fertilization there
      was a low and relatively constant level of actin messenger RNA in the embryo.
      Between 8 and 13 h of development, the amount of actin messenger RNA began to
      increase both in the cytoplasm and on polysomes, and by 18 h the amounts of actin
      message per embryo had risen between approximately 10- and 25-fold in the
      cytoplasm and between 15- and 40-fold on polysomes. Two size classes of actin
      messenger RNA (2.2 and 1.8 kilobases) were identified in unfertilized eggs and in
      all of the developmental stages examined. The amount of each actin message class
      increased over a similar time interval during early development. However, the
      amounts of these size classes in the cytoplasm relative to each other shifted
      between the earliest stages examined (2 to 5 h) and the hatching blastula stage
      (18 h), with the ratio of the 1.8-kilobase actin messenger RNA to the 2.2
      kilobase actin messenger RNA increasing almost threefold during this period.

PMID- 9279385
TI  - Clonal analysis of the late stages of erythroleukemia induced by two distinct
      strains of Friend leukemia virus.
AB  - We observed striking differences between the tumorigenic colony-forming cells
      present in the spleens of mice late after infection with the anemia-inducing
      strain of Friend leukemia virus (strain FV-A) and those present after infection
      with the polycythemia-inducing strain (strain FV-P). Cells within primary
      colonies derived from FV-A- and FV-P-transformed cells (CFU-FV-A and CFU-FV-P,
      respectively) contained hemoglobin and spectrin, indicating that the CFU-FV-A and
      CFU-FV-P were transformed erythroid progenitor cells. The proportion of cells
      containing hemoglobin was relatively high (> 25%) in newly isolated cell lines
      derived from CFU-FV-P colonies, whereas cell lines derived from CFU-FV-A colonies
      had only low levels (0 to 2%) of hemoglobin-containing cells. A high proportion
      of the cell lines derived from CFU-FV-A colonies responded to pure erythropoietin
      and accumulated spectrin and hemoglobin, whereas the cell lines derived from CFU
      FV-P colonies did not. A cytogenetic analysis indicated that primary CFU-FV-P
      colony cells were diploid, whereas chromosomal aberrations were observed in the
      immediate progeny of CFU-FV-A. The presence of unique chromosomal markers in the
      majority of the cells within individual colonies derived from CFU-FV-A suggested
      that these colonies originated from single cells. Finally, leukemic progenitor
      cells transformed by strain FV-A appeared to have an extensive capacity to self
      renew (i.e., form secondary colonies in methylcellulose), whereas a significant
      proportion of the corresponding cells transformed by strain FV-P did not. In
      addition, the self-renewal capacity of both CFU-FV-A and CFU-FV-P increased as
      the disease progressed. From these observations, we propose a model for the
      multistage nature of Friend disease; this model involves clonal evolution and
      expansion from a differentiating population with limited proliferative capacity
      to a population with a high capacity for self-renewal and proliferation.

PMID- 9279386
TI  - Characterization of mouse cellular deoxyribonucleic acid homologous to Abelson
      murine leukemia virus-specific sequences.
AB  - The genome of Abelson murine leukemia virus (A-MuLV) consists of sequences
      derived from both BALB/c mouse deoxyribonucleic acid and the genome of Moloney
      murine leukemia virus. Using deoxyribonucleic acid linear intermediates as a
      source of retroviral deoxyribonucleic acid, we isolated a recombinant plasmid
      which contained 1.9 kilobases of the 3.5-kilobase mouse-derived sequences found
      in A-MuLV (A-MuLV-specific sequences). We used this clone, designated pSA-17, as
      a probe restriction enzyme and Southern blot analyses to examine the arrangement
      of homologous sequences in BALB/c deoxyribonucleic acid (endogenous Abelson
      sequences). The endogenous Abelson sequences within the mouse genome were
      interrupted by noncoding regions, suggesting that a rearrangement of the cell
      sequences was required to produce the sequence found in the virus. Endogenous
      Abelson sequences were arranged similarly in mice that were susceptible to A-MuLV
      tumors and in mice that were resistant to A-MuLV tumors. An examination of three
      BALB/c plasmacytomas and a BALB/c early B-cell tumor likewise revealed no
      alteration in the arrangement of the endogenous Abelson sequences. Homology to
      pSA-17 was also observed in deoxyribonucleic acids prepared from rat, hamster,
      chicken, and human cells. An isolate of A-MuLV which encoded a 160,000-dalton
      transforming protein (P160) contained 700 more base pairs of mouse sequences than
      the standard A-MuLV isolate, which encoded a 120,000-dalton transforming protein
      (P120).

PMID- 9279387
TI  - High-frequency transfer of cloned herpes simplex virus type 1 sequences to
      mammalian cells by protoplast fusion.
AB  - The protoplast fusion technique of Schaffner (W. Schaffner, Proc. Natl. Acad.
      Sci. U.S.A. 77:2163-2167, 1980) has been adapted to introduce cloned herpes
      simplex virus genes into cultured mammalian cells. The technique involves
      digesting bacterial cell walls with lysozyme to produce protoplasts and then
      fusing the protoplasts to mammalian cells by treatment with polyethylene glycol.
      For monitoring transfer, protoplasts were labeled with the fluorescent dye
      fluorescein isothiocyanate before fusion. After fusion, greater than 50% of the
      mammalian cells were fluorescent, demonstrating that bacterial material was
      transferred with high frequency. Transfer of plasmid pBR325 occurred at
      frequencies of 1 to 2%, as measured by in situ hybridization. Fusion transfer of
      a chimeric plasmid consisting of the herpes simplex virus type 1 (strain KOS)
      EcoRI fragment F in pBR325 resulted in expression of some viral genomic sequences
      in about 5% of the mammalian cells, as detected by indirect immunofluorescence.
      One Ltk- cell in 300 to 500 was transformed to the TK+ phenotype after fusion
      with protoplasts carrying the chimeric plasmid pX1, which consists of pBR322 and
      the BamHI fragment coding for the herpes simplex virus type 1 thymidine kinase
      gene.

PMID- 9279388
TI  - Initiation points for cellular deoxyribonucleic acid replication in human
      lymphoid cells converted by Epstein-Barr virus.
AB  - Replicon size was estimated in two Epstein-Barr virus (EBV)-negative human
      lymphoma lines, BJAB and Ramos, and four EBV-positive lines derived from the
      former ones by infection (conversion) with two viral strains, B95-8 and P3HR-1.
      Logarithmic cultures were pulse-labeled with [3H]thymidine, and the
      deoxyribonucleic acid was spread on microscopic slides and autoradiographed by
      the method of Huberman and Riggs. After developing, replication forks were
      visualized as silver grain tracks on the autoradiograms. Average replicon size
      was estimated by scoring the number of replication forks per constant length of
      deoxyribonucleic acid and by measuring distances between centers of adjacent
      tracks, followed by detailed statistical analyses. Three of the four EBV
      converted cell lines, BJAB/B95-8, Ra/B95-8, and Ra/HRIK, were found to have
      significantly shorter replicons (41, 21, 54% shorter, respectively), i.e., more
      initiation points, than their EBV-negative parents. BJAB/HRIK had replicons which
      were only slightly shorter (11%) than those of BJAB. However, analysis of track
      length demonstrated that extensive track fusion occurred during the labeling of
      BJAB/ HRIK, implying that its true average replicon size is shorter than the
      observed value. The results indicate that in analogy to simian virus 40, EBV
      activates new initiation points for cellular DNA replication in EBV-transformed
      cells.

PMID- 9279389
TI  - No activation of new initiation points for deoxyribonucleic acid replication in
      BALB/c 3T3 cells transformed by Kirsten sarcoma virus.
AB  - BALB/c 3T3 cells were transformed by Kirsten sarcoma virus, and five clones were
      isolated in soft agar. Average replicon sizes of the transformed cell lines were
      estimated by the method of fiber-autoradiography (J. A. Huberman and A. D. Riggs,
      J. Mol. Biol.32:327-341, 1968) and found to be the same size as the
      nontransformed 3T3 cells, analyzed in parallel. The results indicate that, unlike
      simian virus 40 and Epstein-Barr virus, Kirsten sarcoma virus does not activate
      new initiation points for cellular deoxyribonucleic acid replication in murine
      sarcoma virus-transformed BALB/c 3T3 cells.

PMID- 9279391
TI  - Striking similarities are exhibited by two small Epstein-Barr virus-encoded
      ribonucleic acids and the adenovirus-associated ribonucleic acids VAI and VAII.
AB  - The nucleotide sequence of the region of the Epstein-Barr virus genome that
      specifies two small ribonucleic acids (RNAs), EBER 1 and EBER 2, has been
      determined. Both of these RNAs are encoded by the right-hand 1,000 base pairs of
      the EcoRI J fragment of EBV deoxyribonucleic acid. EBER 1 is 166 (167)
      nucleotides long and EBER 2 is 172 +/- 1 nucleotides long; the heterogeneity
      resides at the 3' termini. The EBER genes are separated by 161 base pairs and are
      transcribed from the same deoxyribonucleic acid strand. In vitro, both EBER genes
      can be transcribed by RNA polymerase III; sequences homologous to previously
      identified RNA polymerase III intragenic transcription control regions are
      present. Striking similarities are therefore apparent both between the EBERs and
      the two adenovirus-associated RNAs, VAI and VAII, and between the regions of the
      two viral genomes that specify these small RNAs. We have shown that VAII RNA as
      well as VAI RNA and the EBERs exist in ribonucleoprotein complexes which are
      precipitable by anti-La antibodies associated with systemic lupus erythematosus.
      Finally, we have demonstrated that the binding of protein(s) from uninfected
      cells confers antigenicity on each of the four virus-encoded small RNAs.

PMID- 9279392
TI  - Purification of vacuoles from Neurospora crassa.
AB  - The Neurospora crassa vacuole, defined by its content of basic amino acids,
      polyphosphate, protease, phosphatases, and alpha-mannosidase, was purified to
      near homogeneity. The procedure depends upon homogenization of snail gut enzyme
      digested cells in a buffer osmotically stabilized with 1 M sorbitol, differential
      centrifugation of the extract, and sucrose density gradient centrifugation of the
      organellar pellet. Isopycnic centrifugation of vacuoles in 2.25 M sorbitol
      Metrizamide density gradients yielded a peak (density, 1.31 g/cm3) of vacuolar
      markers coincident with 32P-phospholipids, trichloroacetate-insoluble 14C, and
      trichloroacetate-soluble 14C. A trail of macromolecular markers in the lighter
      portions of the gradient reflected, at least in part, heterogeneity of the
      vacuoles. Almost no contamination by mitochondria or glyoxysomes was detected.
      Vacuoles were very heterogeneous in size as estimated by velocity sedimentation,
      but most were larger than mitochondria. Variations of the osmotic strength of the
      medium were found to alter the equilibrium density of vacuole preparations from
      1.06 g/cm3 to over 1.3 g/cm3. This explains the great variation in density
      reported previously for the "vacuole," the "vesicle," and the "protease particle"
      of N. crassa, all of which appear to be the same entity.

PMID- 9279390
TI  - Intracellular monosaccharide and amino acid concentrations and activities and the
      mechanisms of insulin action.
AB  - Current amino acid and monosaccharide transport models are based on an assumption
      which equates the intracellular chemical activity of a solute with its
      concentration. This assumption was tested for alpha-aminoisobutyric acid and 3-O
      methylglucose in a giant cell, the amphibian oocyte, by using recently developed
      cryomicrodissection and internal reference phase techniques. We found the
      following. (i) alpha-Aminoisobutyric acid and 3-O-methylglucose activities were
      much greater in cytoplasm than was suggested by concentration data; i.e.,
      activity coefficients were higher than in ordinary water solutions. This is
      attributable to the inaccessibility of considerable water as solvent (solute
      exclusion). (ii) Solute concentrations varied regionally as follows: nucleus > >
      animal cytoplasm > vegetal cytoplasm. Insulin increased the nucleus/cytoplasm
      concentration asymmetry, apparently by increasing cytoplasmic solute exclusion.
      (iii) Nuclear activity coefficients more closely resembled those of ordinary
      saline solutions so that nucleus/ extracellular concentration ratios reflected
      transmembrane activity gradients better than did cytoplasm (or whole
      cell)/extracellular ratios. (iv) Mediated passive alpha-aminoisobutyric acid and
      3-O-methylglucose transport were constituent oocyte membrane properties. Membrane
      active transport was initiated with time (in the presence of substrate) and by
      insulin. (v) Increased temperature mimicked insulin in enhancing transmembrane
      alpha-aminoisobutyric acid activity gradients and increasing the
      nucleus/cytoplasm concentration asymmetry. These results indicated that
      concentration data are a misleading measure of cellular amino acid and
      monosaccharide activity; some consequences of this observation were explored. A
      model is proposed in which cell water has reduced solvent capacity or is
      compartmentalized (considered less likely) and is susceptible to physiological
      modulation. The model accounts for many observations in small cells, suggesting
      generality of the exclusion phenomenon and a previously unrecognized metabolic
      control mechanism.

PMID- 9279394
TI  - Linkage and evolutionary diversification of developmentally regulated multigene
      families: tandem arrays of the 401/18 chorion gene pair in silkmoths.
AB  - The coordinately expressed silkmoth chorion genes, 401 and 18, are closely linked
      as a pair, in divergent orientation. Analysis of overlapping clones (chromosomal
      "walk") demonstrated that each of the multiple copies of this gene pair is
      embedded within a larger deoxyribonucleic acid unit, which is tandemly repeated
      in a few arrays or possibly a single array. Southern analysis and examination of
      clones from a single individual moth demonstrated that the repeat units are
      extensively polymorphic in restriction sites, length, and possibly number, no
      differential amplification was evident during choriogenesis. Intron and 5'
      flanking sequences were shown to be specific for the 401/18 gene pair and not to
      be present elsewhere in the genome. The spatial distribution of variations in the
      genes and their flanking sequences were examined.

PMID- 9279393
TI  - Control of adenovirus early gene expression: posttranscriptional control mediated
      by both viral and cellular gene products.
AB  - An adenovirus type 5 host range mutant (hr-1) located in region E1A and
      phenotypically defective in expressing viral messenger ribonucleic acid (RNA)
      from other early regions (Berk et al., Cell 17:935-944, 1979) was analyzed for
      accumulation of viral RNA in the presence of protein synthesis inhibitors.
      Nuclear RNA was transcribed from all early regions at the same rate, regardless
      of whether the drug was present or absent. As expected, low or undetectable
      levels of RNA were found in the cytoplasm of hr-1-infected cells compared with
      the wild-type adenovirus type 5 in the absence of drug. When anisomycin was added
      30 min before hr-1 infection, cytoplasmic RNA was abundant from early regions E3
      and E4 when assayed by filter hybridization. In accordance, early regions E3 and
      E4 viral messenger RNA species were detected by the S1 endonuclease mapping
      technique only in hr-1-infected cells that were treated with the drug. Similar
      results were obtained by in vitro translation studies. Together, these results
      suggest that this adenovirus type 5 mutant lacks a viral gene product necessary
      for accumulation of viral messenger RNA, but not for transcription. It is
      proposed that a cellular gene product serves as a negative regulator of viral
      messenger RNA accumulation at the posttranscriptional level.

PMID- 9279395
TI  - Genetic regulation of the qa gene cluster of Neurospora crassa: induction of qa
      messenger ribonucleic acid and dependency on qa-1 function.
AB  - An in vitro protein-synthesizing system (rabbit reticulocyte) was programmed with
      total polyadenylated messenger ribonucleic acid from wild type and various
      mutants in the qa gene cluster of Neurospora crassa. The products of two of the
      qa genes, quinate dehydrogenase (qa-3+) and dehydroshikimate dehydratase (qa-4+),
      were identified by specific immunoprecipitation and sodium dodecyl sulfate-slab
      gel electrophoresis. The results indicated that for both genes induction of a
      specific enzyme activity by quinic acid depends on the de novo synthesis of a
      specific polypeptide and on the de novo appearance of specific messenger
      ribonucleic acid detectable by the in vitro translation assay. Furthermore, the
      results indicated that the appearance of this messenger ribonucleic acid is under
      the control of the qa-1 gene. The simplest interpretation of these results
      appears to be that induction of enzyme activity in the qa system is mediated by
      events at the transcriptional level.

PMID- 9279396
TI  - Genetic complementation of the Saccharomyces cerevisiae leu2 gene by the
      Escherichia coli leuB gene.
AB  - The leucine operon of Escherichia coli was cloned on a plasmid possessing both E.
      coli and Saccharomyces cerevisiae replication origins. This plasmid, pEH25,
      transformed leuA, leuB, and leuD auxotrophs of E. coli to prototrophy; it also
      transformed leu2 auxotrophs of S. cerevisiae to prototrophy. beta-Isopropylmalate
      dehydrogenase was encoded by the leuB gene of E. coli and the leu2 gene of yeast.
      Verification that the leuB gene present on pEH26 was responsible for
      complementing yeast leu2 was obtained by isolating in E. coli several leuB
      mutations that resided on the plasmid. These mutant leuB- plasmids were no longer
      capable of complementing leu2 in S. cerevisiae. We conclude that S. cerevisiae is
      capable of transcribing at least a portion of the polycistronic leu operon of E.
      coli and can translate a functional protein from at least the second gene of this
      operon. The yeast Leu+ transformants obtained with pEH25, when cultured in
      minimal medium lacking leucine, grew with a doubling time three to four times
      longer than when cultured in medium supplemented with leucine.

PMID- 9279397
TI  - Ascorbate induction of collagen synthesis as a means for elucidating a mechanism
      of quantitative control of tissue-specific function.
AB  - Ascorbic acid displays the characteristics of an ideal inducer of tissue-specific
      function in primary avian tendon cells in culture. It is a highly specific,
      potent stimulator of collagen synthesis, it demonstrates slow reversible
      kinetics, and it has no effect on growth rate of the cultured cells. Kinetic
      analysis of ascorbate induction of collagen synthesis was used to determine the
      critical steps in this complex biosynthetic pathway. Full hydroxylation of the
      proline residues in collagen, although probably a necessary step for collagen
      induction, was in itself not sufficient for achieving either increased secretion
      or increased synthesis. On the other hand, an increase in secretion rate, which
      required both the presence of ascorbate and a high cell density, did correlate
      with the later stimulation in procollagen production. The process of procollagen
      secretion, therefore, meets the minimal requirements for the rate-limiting step.
      The fact that the cells maintained a large pool of intracellular procollagen
      despite changes in the rates of translation or secretion led us to postulate a
      possible feedback between the level of the internal procollagen pool and the rate
      of procollagen synthesis.

PMID- 9279399
TI  - Control of initiation and elongation of cilia during ciliary regeneration in
      Tetrahymena.
AB  - Tetrahymena thermophila strain B could regenerate approximately 10% of its
      somatic ciliary mass in concentrations of cycloheximide believed to block all
      cytoplasmic protein synthesis. A quantitative study of the relative numbers and
      lengths of cilia regenerated in the presence and absence of cycloheximide under a
      variety of conditions suggested that specific initiation and elongation protein
      factors are involved in the control of ciliary morphogenesis in Tetrahymena.

PMID- 9279400
TI  - Think link: critically evaluating linkages between conservation projects and
      development.

PMID- 9279398
TI  - Expression of the mouse dihydrofolate reductase complementary deoxyribonucleic
      acid in simian virus 40 vectors.
AB  - A mouse complementary deoxyribonucleic acid segment coding for the enzyme
      dihydrofolate reductase has been cloned in two general classes of vectors
      containing simian virus 40 deoxyribonucleic acid: (i) those that can be
      propagated as virions in permissive cells and (ii) those that can be introduced
      into and maintained stably in various mammalian cells. Both types of vectors
      express the mouse dihydrofolate reductase by using signals supplied by simian
      virus 40 deoxyribonucleic acid sequences. Moreover, plasmid vectors carrying the
      complementary deoxyribonucleic acid segment can complement Chinese hamster ovary
      cells lacking dihydrofolate reductase.

PMID- 9279401
TI  - Plasma alpha-tocopherol, beta-carotene, and lipid levels in semi-free-ranging
      Przewalski horses (Equus przewalskii).
AB  - Circulating concentrations of alpha-tocopherol, beta-carotene, and lipids were
      quantified in 19 Przewalski horses (Equus przewalskii) inhabiting the steppes of
      Ukraine during June 1991. Foals (n = 3) had lower mean plasma alpha-tocopherol
      (4.7 micrograms/ml) and beta-carotene (0.3 microgram/ml) levels than did adults
      (n = 16; 6.6 and 0.7 micrograms/ml, respectively) and higher mean cholesterol
      concentrations (1.42 vs. 0.98 mg/ml). Mean triglyceride levels did not differ
      between foals and adults (0.46 mg/ml). Alpha tocopherol concentrations were
      substantially higher than those considered normal for domestic and zoo equids,
      but beta-carotene, cholesterol, and triglyceride levels were within expected
      ranges. These limited data suggest excellent circulating vitamin E concentrations
      in these horses and may provide useful comparative guidelines for assessment of
      fat-soluble nutrient concentrations and establishment of optimal dietary
      management of Przewalski horses.

PMID- 9279402
TI  - Fecal shedding of Salmonella in exotic felids.
AB  - Two collections of exotic felids were screened for the presence of Salmonella by
      selective fecal culture utilizing selenite broth and Hektoen enteric agar. In >
      90% of the samples, Salmonella was isolated from a single culture. A commercial
      horsemeat-based diet was fed in both collections, and one collection also was fed
      raw chicken. Salmonella was cultured from the raw chicken and the horsemeat diet
      for both collections. Multiple Salmonella serotypes were identified, with S.
      typhimurium and S. typhimurium (copenhagen) isolated most frequently.
      Approximately half of the Salmonella isolates demonstrated multiple antibiotic
      resistance. The ability to harbor Salmonella as normal nonpathogenic bacteria of
      the gastrointestinal tract may be a physiological adaptation to carnivory. The
      high rate of fecal shedding of Salmonella in healthy individuals clouds the
      interpretation of a positive fecal culture in an ill felid, or one with diarrhea.
      All zoo employees having contact with cat feces or raw diets have a high rate of
      occupational exposure to Salmonella and should exercise appropriate hygienic
      precautions.

PMID- 9279403
TI  - Encephalomyocarditis virus infections in an Australian zoo.
AB  - Fatal encephalomyocarditis virus (EMCV) infections in a ring-tailed lemur (Lemur
      catta), a squirrel monkey (Saimiri sciureus), three mandrills (Mandrillus
      sphinx), a chimpanzee (Pan troglodytes), a pygmy hippopotamus (Choeropsis
      liberiensis), and two Goodfellows tree kangaroos (Dendrolagus goodfellowi)
      occurred at Taronga Zoo. This is the first description of EMCV in a zoological
      collection outside of the United States. Regardless of species, the most common
      clinical presentation was sudden death. The gross pathologic changes were diffuse
      or focal pallor of the myocardium with occasional marked pulmonary congestion.
      Necrotizing nonsuppurative myocarditis was consistently present. EMCV was
      isolated from only one of 54 feral rodents examined. No antibodies to EMCV were
      detected with a serum neutralization test in 79 stored sera from a wide variety
      of zoo mammals. Titers of 1:16, 1:16, and 1:4 were recorded for a spider monkey
      (Aeteles geoffroyi), a lion (Panthera leo), and an orangutan (Pongo pygmaeus),
      respectively. Of seven mandrills tested in 1988, six had measurable virus titers.
      Later testing indicated that these titers did not persist, and one mandrill with
      a titer > 1:128 in 1988 subsequently succumbed to EMCV infection in 1991.

PMID- 9279404
TI  - Immobilization of domestic goats (Capra hircus) using orally administered
      carfentanil citrate and detomidine hydrochloride.
AB  - Eight domestic goats (Capra hircus) were anesthetized with a combination of
      carfentanil citrate and detomidine HCl each at a dosage of 60 micrograms/kg,
      mixed with an equal volume of 0.5% saponin, an absorption enhancer. The drug
      combination was delivered by hand directly into the buccal cavity. Physiologic
      parameters were measured prior to drug administration and at 5-min intervals
      after the goats reached sternal recumbency. Depth of anesthesia was assessed at
      the same time intervals following drug administration. Blood was drawn prior to
      drug administration, at initial contact following sustained sternal recumbency,
      and at 15-min intervals thereafter. Serum carfentanil and detomidine levels were
      measured using slightly modified commercial enzyme-linked immunosorbent assay
      kits and techniques. Mean (+/-SD) induction time (time from drug administration
      to sternal recumbency) was 22 +/- 4.3 min (n = 8), and inductions were
      characterized by long excitement phases (9.3 +/- 5.8 min). There was considerable
      variation in the depth of anesthesia. Three goats appeared to be lightly
      anesthetized, two goats showed moderate levels of anesthesia, and three goats
      attained levels of anesthesia adequate for the performance of minor veterinary
      procedures. Physiologic changes caused by the drug combination were minor and
      were consistent with changes seen with parenteral administration of these drugs.
      Serum carfentanil levels were greatest at the time of initial contact for three
      goats and greatest 15 min later for two other goats. Levels then decreased
      slightly during the procedures, suggesting carfentanil absorption in these
      animals was across the oral mucosa. Serum detomidine levels rose gradually
      throughout anesthesia. Reversals with naltrexone and yohimbine or atipamezole
      were rapid and smooth.

PMID- 9279405
TI  - Cardiopulmonary effects of carfentanil in dama gazelles (Gazella dama).
AB  - Sixteen (10 female, six male) captive-born dama gazelles (Gazella dama) weighing
      48 +/- 10 kg (mean +/- SD) were used to evaluate the cardiopulmonary effects of
      i.m. carfentanil and to validate the use of pulse oximetry in immobilized
      gazelles. Carfentanil (18.4 +/- 2.2 micrograms/kg i.m.) produced rapid induction
      (6 +/- 3 min), moderate muscle relaxation, and a significant (P < 0.05) decrease
      in heart rate (87 +/- 12 beats/min) beginning 5 min following induction and
      continuing throughout the immobilization period. A decrease in respiratory rates
      began 15 min following induction (11 +/- 4 breaths/min). Systemic hypertension
      was present throughout the immobilization period. Arterial blood gas analysis,
      performed at 10, 20, and 30 min after induction, showed PaCO2 and PaO2 values
      within normal limits. Arterial blood oxygen saturation (SaO2) was < 95% 10 min
      after induction. Relative arterial oxygen saturation (SpO2) values indicated by
      pulse oximetry were generally lower than SaO2 values but reliably demonstrated
      trends in arterial oxygen saturation as confirmed by arterial blood gas analysis.
      Periods of hypoxemia were usually indicated by the pulse oximeter reading and
      confirmed by SaO2 measurements. There was an increase in creatine phosphokinase
      values (88 +/- 53 U/L to 109 +/- 48 U/L) at 30 min postimmobilization. Naltrexone
      reversal (1.8 +/- 0.3 mg/kg, half i.v. and half s.c.) was rapid and uneventful,
      and time to standing was 2 +/- 1 min.

PMID- 9279406
TI  - Serum chemistry and hematology values for anesthetized American bullfrogs (Rana
      catesbeiana).
AB  - Samples taken from seven male and seven female adult American bullfrogs (Rana
      catesbeiana) were evaluated by complete blood count and serum chemistry to
      establish baseline data on commercially available frogs destined for laboratory
      use. Differences between sexes were analyzed and females had higher plasma
      protein, calcium, and sodium levels.

PMID- 9279407
TI  - Cryptococcosis in tree shrews (Tupaia tana and Tupaia minor) and elephant shrews
      (Macroscelides proboscides).
AB  - Fungal infections due to Cryptococcus neoformans occurred in seven short-eared
      elephant shrews (Macroscelides proboscides), six large tree shrews (Tupaia tana),
      and five lesser tree shrews (Tupaia minor) at the National Zoological Park during
      a 30-mo period in 1991-1993. Clinical signs were absent or included weight loss,
      shivering, dyspnea, and/or neurologic disease. Definitive antemortem diagnostic
      techniques included tracheal lavage and serum cryptococcal antigen latex
      agglutination titers. Thirteen cases were diagnosed solely by postmortem
      examination. The source of infection for these animals was uncertain, but C.
      neoformans is commonly found in soil and other organic material. Two lesser tree
      shrews and one large tree shrew received antifungal therapy and converted to a
      negative serum cryptococcal antigen titer.

PMID- 9279408
TI  - Serial tranquilization of a reticulated giraffe (Giraffa camelopardalis
      reticulata) using xylazine.
AB  - A 5-yr-old captive-born reticulated giraffe (Giraffa camelopardalis reticulata)
      was tranquilized with i.m. xylazine 34 times in a 39-day period to allow nursing
      by her calf. Xylazine administered at approximately 0.16 mg/kg i.m. provided
      adequate sedation of the dam without detrimental side effects to the dam or the
      calf. While the dam was sedated, the calf was able to ingest adequate amounts of
      milk to produce acceptable weight gains until he was consistently eating solid
      foods.

PMID- 9279409
TI  - Mycobacterium avium-intracellulare infection in a white-faced saki (Pithecia
      pithecia).
AB  - Physical examination of an adult female white-faced saki (Pithecia pithecia)
      revealed midabdominal multiple cystic structures. The animal developed a grade
      3/4 reaction to old mammalian tuberculin injected into the right eyelid.
      Significant clinicopathologic findings included marked hyperproteinemia (9.2
      g/dl), hyperglobulinemia (6.1 g/dl), and hypoalbuminemia (3.1 g/dl).
      Ultrasonography revealed multiple abdominal masses of varying echogenicity. The
      animal was euthanized and necropsied. Significant histopathologic findings
      included multifocal lymphadenitis with cystic degeneration of multiple visceral
      lymph nodes. Mycobacterium avium-intracellulare was cultured from a mesenteric
      lymph node.

PMID- 9279410
TI  - Magnetic resonance imaging and computerized tomography of a gravid leopard
      tortoise (Geochelone pardalis pardalis) with metabolic bone disease.
AB  - Secondary nutritional metabolic bone disease was diagnosed in a gravid leopard
      tortoise (Geochelone pardalis pardalis). Diagnosis was based upon history,
      physical examination, hematology, plasma biochemistry, and radiography. Despite
      induced oviposition and treatment of metabolic bone disease for 8 wk, the
      tortoise's condition deteriorated. Repeat radiographs demonstrated gaseous
      intestinal distention. Oral administration of metoclopramide and mineral oil
      failed to stimulate defecation. Persistence of the ileus pattern prompted
      utilization of magnetic resonance imaging (MRI) and computerized tomography (CT).
      MRI demonstrated brightly enhanced loops of mineral oil-filled small bowel and
      preovulatory follicles. CT demonstrated dystrophic calcification of the left
      hepatic lobe and preovulatory follicles and the typical reticular pattern of
      chelonian lung. The interstitial septa were caused by pulmonary vasculature or
      bands of smooth muscle.

PMID- 9279411
TI  - Malignant chromatophoroma in a canebrake rattlesnake (Crotalus horridus
      atricaudatus).
AB  - An adult female canebrake rattlesnake (Crotalus horridus atricaudatus) at Zoo
      Atlanta (Atlanta, Georgia, USA) had a subcutaneous mass on the left lateral
      abdomen. Microscopically, the tumor contained a pleomorphic population of cells
      with abundant intracytoplasmic brown to gold nonrefractile pigment
      (chromatophores), large stellate cells resembling neurons, and small stellate
      cells whose cytoplasmic processes formed a fibrillar matrix. The pigment stained
      black with the Fontana-Masson technique and was positive with the periodic acid
      Schiff technique (prior to and after diastase treatment). Neuron-specific enolase
      was detected in the large stellate cells using an immunohistochemical staining
      technique. In addition, glial fibrillary acidic and S-100 proteins were detected
      in the chromatophores with immunohistochemical staining. The smaller stellate
      cells were strongly S-100 positive. Ultrastructurally, chromatophores contained
      intracytoplasmic structures composed of concentric lamellar membranes bordered by
      a triple-layer outer membrane. The morphology of these structures was compatible
      with pterinosomes. Three fluorescent pigments were isolated from the neoplasm by
      one-dimensional chromatography and characterized by spectrophotometry and
      spectrofluorometry.

PMID- 9279412
TI  - Naturally occurring cerebral nematodiasis due to Baylisascaris larval migration
      in two black-and-white ruffed lemurs (Varecia variegata variegata) and suspected
      cases in three emus (Dromaius novaehollandiae).
AB  - During September and October 1992, two black-and-white ruffed lemurs (Varecia
      variegata variegata) were housed in an outdoor wire enclosure at the Tulsa
      Zoological Park. The following February and April, both lemurs developed head
      tilt and ataxia, and they were euthanized. Necropsy revealed multifocal malacia
      of the white matter of the pons, cerebellum, internal capsule, and cerebral and
      cerebellar peduncles. Nematode larvae consistent with Baylisascaris spp. were
      observed in the brain of one lemur. A retrospective study revealed three cases of
      ataxia in emus (Dromaius novaeholloandiae) that were previously housed in the
      same enclosure. Archival paraffin-embedded tissue from one emu revealed tractlike
      foci of malacia within the white matter of the cerebellum. Circumstantial
      evidence, including the observation of numerous raccoons (Procyon lotor) in the
      vicinity, and the presence of numerous Baylisascaris. procyonis in the intestine
      of a single trapped raccoon implicate this roundworm as the pathologic agent in
      the lemurs.

PMID- 9279413
TI  - Surgical removal of infected phalanges from an Asian elephant (Elephas maximus).
AB  - A 40-yr-old female Asian elephant (Elephas maximus) developed cellulitis and
      became lame in her left front leg. A draining tract behind the lateral nail of
      her left front foot was discovered. This lesion was treated by aggressive
      irrigation using a variety of disinfectant solutions. Radiographically, there was
      degeneration and fragmentation of the distal phalanx of the fifth digit and
      patterns suggestive of osteomyelitis of the second (middle) phalanx. The
      fragments of the distal phalanx and the affected portion of the second phalanx
      were removed surgically. Six months after surgery the incision had healed but a
      fistulous tract remained on the palmar surface of the foot. The tract extended to
      the second phalanx, and there was radiographic evidence of osteomyelitis in the
      second phalanx and the distal portion of the proximal phalanx. The remainder of
      the second phalanx and the distal portion of the proximal phalanx were surgically
      removed. Aggressive aftercare allowed complete wound closure by second intention.

PMID- 9279414
TI  - Chlamydiosis in a fishing cat (Felis viverrina).
AB  - A fishing cat (Felis viverrina) died overnight, within 12 hr of peracute onset of
      depression, slight tremors, pallor, and icterus. Necropsy showed widespread
      hemorrhage and hematomata in the heart, stomach, and kidneys. The lungs were
      hyperemic and edematous. The liver was swollen and yellowish green. The spleen
      was very large and hyperemic. Histologic changes consisted of pneumonia, hepatic
      necrosis, and renal hemorrhage with glomerular fibrin clots. Chlamydia antigen
      was detected in liver and kidney using a direct immunofluorescence assay, and
      Chlamydia were cultured.

PMID- 9279416
TI  - Clinical challenge. Parelaphostrongylus tenuis (meningeal worm) infection of the
      cranial spinal cord and brain stem.

PMID- 9279415
TI  - Treatment of bilateral nasal polyposis and chronic refractory inhalant allergic
      rhinitis in a chimpanzee (Pan troglodytes).
AB  - Over a 15-yr time span, a 30-yr-old female chimpanzee (Pan troglodytes) exhibited
      recurrent upper respiratory disease that was suspected to be allergen induced.
      Until 1993, symptomatic therapy with several different antibiotics and
      antihistamines yielded variable results. In early 1993, the chimpanzee was
      consistently observed to be open-mouth breathing despite medication. Nasal
      polyposis was diagnosed using rigid endoscopy in September 1993, and the polyps
      were removed by loop excision. A fluorescent allergosorbent test was performed to
      differentiate hypersensitivity to specific regional allergens causing chronic
      inhalant allergic rhinitis. Oral immunotherapy was then instituted using standard
      human treatment for Sacramento Valley pollens. This combination of polyp removal
      and immunotherapy resulted in a marked reduction of clinical signs, and
      continuous oral immunotherapy has controlled these signs. Hyposensitization
      therapy will continue for at least 2-3 yr. The chimpanzee continues to breath
      normally following occasional antihistamine treatment.

PMID- 9279417
TI  - Syntactic bootstrapping in children with specific language impairment.
AB  - Syntactic bootstrapping was assessed in six children with normally developing
      language (NL) and six children with specific language impairment (SLI), ages 6
      and 8, respectively. Children earned normal range non-verbal IQs and were matched
      by raw scores on a test of sentence comprehension. They were asked to listen to
      sentences containing novel verbs and to act out the meanings with toys. The SLI
      children earned reliably lower scores, but their errors suggested processing
      limitations rather than deficits in syntactic representation.

PMID- 9279418
TI  - The development of morphology and syntax in a pair of DZ twin boys.
AB  - Twins provide a natural set-up for the study of some of the basic issues that
      concern the field of language acquisition and of developmental language disorders
      and brain pathology, in that they present a unique hereditary and environmental
      situation within which development takes place. Yet, few studies have detailed
      the development of formal aspects of language in twins. This paper reports on a
      prospective, longitudinal study of the acquisition of selected aspects of Hebrew
      syntax and morphology in a pair of DZ twin boys, aged 3;6-4;0, one of whom had a
      congenital brain abnormality. MLU levels suggest a marked delay for both children
      in the onset and progression of language development. However, both the healthy
      and the brain-injured twin followed a normal developmental course. Data to that
      effect concern frequency of sentences of various lengths, distribution of
      sentence types, use of tenses, use of pronouns, correct usage of various
      syntactic markers, variability of verb types and tokens and the distribution of
      errors of morphology and morphophonology. It is argued that this case study
      offers support for claims concerning brain plasticity for language. Furthermore,
      it is in line with previous studies of normal and brain-injured children which,
      rather unexpectedly, pointed at the relative ease with which formal, linguistic
      systems were acquired.

PMID- 9279419
TI  - The Lidcombe Programme of early stuttering intervention: methods and issues.
AB  - The Lidcombe Programme is an operant intervention for early stuttering that
      parents administer to children in their everyday speaking environments. The
      treatment was developed at the Suttering Unit, Bankstown Health Service, Sydney,
      and The University of Sydney. Recently, staff from the Australian Stuttering
      Research Centre. The University of Sydney, toured universities and clinics in the
      UK to present lectures about this treatment. We were encouraged to write this
      paper because an independent survey showed that most speech and language
      therapists who attended the presentations were open to this treatment. Prior to
      and following that lecture tour, publications in the press and professional
      journals in the UK alluded to many positive features of the Lidcombe Programme,
      but also raised several issues about it. The purpose of this paper is to
      summarise the Lidcombe Programme and address the following criticisms of the
      treatment that were raised in the UK: (1) Stuttering is complex but the Lidcombe
      Programme is simple; (2) the Lidcombe Programme is not an operant treatment, but
      invokes positive changes in children's environments; (3) the Lidcombe Programme
      is harmful to children; and (4) the scientific evidence in support of the
      Lidcombe Programme is flawed. Each of these issues is addressed from logical,
      theoretical and empirical viewpoints.

PMID- 9279420
TI  - Commentary on the Lidcombe Programme of early stuttering intervention.
AB  - Dr Onslow's brief articles and his lecture tour in the UK generated interested in
      the UK because the Lidcombe Programme appeared to offer the possibility of a new,
      simple and effective package for use with young stammering children. This
      commentary has sought to examine these aspects more objectively by careful
      consideration of the paper submitted to this Journal and others. It would seem of
      great importance to reflect on the theoretical issues which have been covered as
      well as the relative complexity of the Lidcombe Programme compared with the
      approaches that are in common usage now in specialist centres in the UK. Dr
      Onslow and his colleagues have given us an opportunity to highlight the
      importance of working with young stammering children and we would hope that the
      interest that they have created will inspire colleagues to investigate further
      training opportunities for working with this very rewarding client group.

PMID- 9279421
TI  - Commentary on Onslow, O'Brian and Harrison.

PMID- 9279422
TI  - Bilingualism and specific language impairment in children attending language
      units.
AB  - Bilingual children were found to form a distinct subgroup within a large cohort
      of children with specific language-impairment (SLI) attending language units
      across England. They differed from the cohort as a whole, and from a language
      matched monolingual 'control' group, on measures including language profile on
      entry to the unit, performance on standardised tests, emotional-behavioural state
      and probable future educational placement. This paper sets out the nature of
      these differences in more detail, and suggests some possible explanations for
      them.

PMID- 9279423
TI  - Phonological impairment in dyslexic children with and without early speech
      language disorder.
AB  - This study examines phonological awareness in a group of 10 dyslexic children,
      compared with two groups of children (a reading-equivalent control group and a
      group of beginning readers). Five of the dyslexic children exhibited an early
      speech-language impairement, and five others were not language-impaired. The
      experimental design consisted of a set of 10 tasks involving sensitivity to
      phonological strings, phonetic identification, and phoneme segmentation and
      manipulation. The major findings reveal that (a) the two subgroups of dyslexic
      children exhibit a metalinguistic impairment and (b) dyslexic children with
      speech-language impairment exhibit (besides metalinguistic impairment) a deficit
      concerning early precursors of the phonological awareness (rhyme and syllables).
      These findings provide additional support for including speech-language
      impairment as an operational criterion within the heterogeneous group of dyslexic
      children.

PMID- 9279424
TI  - Evaluating intervention for language impaired children: a review of the
      literature.
AB  - Intervention studies are divided into those which have examined the effectiveness
      of specific techniques and those that have attempted to examine efficacy within
      the clinical context. Of the specific techniques, imitation and recasting or
      expansion have been the most commonly examined. Results suggest that they may be
      equally useful in reaching targets but that input in context has more chance of
      generalising. Combinations of techniques such as 'milieu teaching' seem
      especially promising. Evaluation of general language training strategies has
      tended to show good results relative to controls, although care has to be taken
      to discriminate between changes brought about to interaction skills and those to
      specific linguistic structures. The paper also covers issues associated with
      evaluation including clinical outcomes and methodological considerations. A
      number of research directions are suggested.

PMID- 9279426
TI  - Why pragmatic impairment? A case study in the comprehension of inferential
      meaning.
AB  - This paper discusses a case study of Sarah (aged 9;8-10;3) who is reported to
      have pragmatic difficulties. The focus is on her comprehension of questions,
      which are asked on the basis of pictures and heard stories. Particular focus is
      on the pragmatic (or inferential) demands of the input questions and their
      relationship to the (in)appropriacy of the answer. Data from 16 normally
      functioning 6- and 8-year-old children are also presented for comparative
      purposes. The study shows that Sarah has difficulty with questions which require
      her to go beyond visually presented or verbally stated information. On one set of
      tasks she was to answer questions on the basis of composite pictures: for some of
      the questions, the answer was obvious from the picture (descriptive questions)
      and for others information needed to be inferred beyond the picture (for example,
      by imagining what had happened before and what is likely to happen next). Sarah's
      performance was poorer on the inferential questions than the descriptive
      questions and poorer than the performance of 6- and 8-year-old normally
      functioning control children. Although the control children also found the
      inferential questions more difficult than the descriptive questions, this
      difficulty was not as pronounced as Sarah's. This trend was also apparent in a
      set of tasks which required the children to answer questions on the basis of
      verbally told stories. This study suggests that pragmatically impaired children
      may have difficulty going beyond explicitly presented information and this would
      manifest as pragmatic production and comprehension problems. In cognitive terms,
      this may indicate difficulty with the process of inferencing.

PMID- 9279425
TI  - Verbs in the emergence of word combinations in young children with specific
      expressive language impairment.
AB  - Young children with specific expressive language impairment (SELI) are typically
      first identified by their delay in initial vocabulary learning. When their
      language difficulties persist they often have problems with verb constructions.
      The purpose of the present study was to examine the role of lexical development
      in children with SELI who were moving from the single-word to the multi-word
      stage of language production, with particular attention to verbs. The research
      examined the nature of the developing lexicon (lexicon size and composition) and
      realisation of lexical categories and their combinatorial properties transitivity
      of verbs) as the children began producing word combinations during a nine-week
      period of observation, three weeks of which involved treatment. Results indicated
      a moderate correlation between the developing lexicon, both in size and
      composition of vocabulary, and the emergence of word combinations as measured by
      mean length of utterance. Further, the data revealed the importance of
      intransitive and ditransitive verbs for children who demonstrated the greatest
      change in their language production. The findings are discussed in terms of their
      theoretical and clinical importance.

PMID- 9279427
TI  - Referential communication tasks: performance by normal and pragmatically impaired
      children.
AB  - Two groups of children, a pragmatically impaired (PI) group and a group of
      language-normal (LN) age-matched peers, were compared by use of a referential
      communication task. Experimenter and child both played the roles of listener and
      instructor during the task and, in addition, the experimenter sometimes failed to
      give adequate information when in the role of instructor. Lexical content and
      structural complexity were controlled, and it was hypothesised that difficulties
      for the PI group would arise when in the role of instructor, as a result of
      failing to specify necessary information in order for the experimenter to respond
      appropriately. In fact, the main difference between the two groups arose when the
      experimenter failed to give adequate information to the child; the LN children
      were quick to realise this and to request clarification, whereas the PI children
      requested clarification to a lesser extent and appeared less aware of the need to
      do so. Possible explanations for this pattern of results are explored.

PMID- 9279428
TI  - Enhancing the phonological processing skills of children with specific reading
      disability.
AB  - The present study evaluated the benefits of phonological processing skills
      training for children with persistent reading difficulties. Children aged between
      9-14 years, identified as having a specific reading disability, participated in
      the study. In a series of three experiments, pedagogical issues related to length
      of training time, model of intervention and severity of readers' phonological
      processing skills deficit prior to intervention, were explored. The results
      indicated that improvement in poor readers' phonological processing skills led to
      a dramatic improvement in their reading accuracy and reading comprehension
      performance. Increasing the length of training time significantly improved
      transfer effects to the reading process. Children with particularly severe
      phonological processing skill deficits benefited from an extended training
      period, and both individual and group intervention models for phonological
      processing training proved successful. Implications for speech and language
      therapists are discussed.

PMID- 9279429
TI  - Phonological processing skills in speech and language impaired children.
AB  - Phonological processing has been shown by many researchers to be strongly related
      to the acquisition of reading and spelling skills. Children with speech and
      language impairment appear to be at increased risk for phonological processing
      problems and hence literary difficulties. However, not all children with speech
      and language impairment experience difficulties: the literature is not clear as
      to which groups of speech and language impaired children are most severely
      affected nor which aspects of phonological processing are most likely to be
      impaired. Rigorous subject selection was employed to compare the performance of
      four groups of 20 children, aged approximately 6 years: speech-impaired (Speech);
      language-impaired (Language); speech and language impaired (Mixed); and children
      with normally developing language (Normal), by use of a battery of phonological
      processing tasks. The results supported the research that has shown speech and
      language impaired children to have weaker phonological processing skills than the
      general population. All the subjects in this sample appeared to be at risk: the
      Mixed children demonstrated the most difficulty, followed by the Language group,
      with the Normal group performing the best. Whilst the Speech group as a whole
      performed significantly more poorly than the Normal group, it consisted of two
      levels of performance which, on post hoc analysis were shown to relate to the
      pattern of speech impairment exhibited by the child.

PMID- 9279430
TI  - Autism and meta-representation: the case of epistemic modality.
AB  - This paper investigates the meta-representational abilities of high-functioning
      autistic adults on the basis of their use of linguistic expression forms of
      epistemic modality. The investigation is based on data drawn from natural
      conversations (in Dutch) with four autistic subjects with varying IQ levels.
      Parallel to an existing in-depth corpus study of epistemic modal expression forms
      in normal language use (i.e. the 'control data' for the present study), the
      occurrences in the data of four types of such expression forms--modal adverbs
      (ADV), predicative adjectives (ADJ), mental state predicates (MSP), and
      auxiliaries (AUX)--are analysed in terms of their quantitative and qualitative
      comparability to the normal data. The results show normal usage of these forms
      for three of the subjects. Only one subject, with the lowest general IQ of the
      four, shows problems with particular types of usages. It is argued that these
      results show that although there is some truth to the classical 'Theory of Mind'
      theories of autism, they turn out to be too simple to account for the data.
      Suggestions for an alternative way of thinking about the nature of autism are
      offered.

PMID- 9279431
TI  - Secondary prevention of paediatric language disability: a comparison of parents
      and nurses as screening agents.
AB  - The purpose of this investigation was to compare the ability of nurses and
      parents to detect speech and language disability. The methodology included
      development and validation of a parent questionnaire to detect speech and
      language disability in 398 3-year-old English-speaking children. The parent
      questionnaire and a standard developmental screen administered by child health
      nurses were compared with a gold standard (a speech and language assessment).
      International criteria for screening tools were applied. The tools were
      comparable in performance. A simple parent questionnaire, completed without
      professional assistance, was a viable alternative to professional screening.
      Parents' education and parity had no influence on their ability to detect
      language disorders. Although size of sibship had no association with the
      occurrence of speech and language disability, third-born children were more
      likely to have a speech and language disability than any other birth order.

PMID- 9279432
TI  - Spatial cognition in language-impaired children.
AB  - Limited research evidence is available concerning the spatial abilities of
      children with specific language impairments. This paper reports a study of the
      ability of such children to use plan drawings. The participants were 23 language
      impaired (LI) children (12 from special boarding schools, 11 from language units
      within mainstream primary schools), whose performance was compared with that of
      23 non-language-impaired (NLI) children. The children were matched for age, their
      overall age range being between 7;0-11;11 (mean age 8;6). Tasks involved the
      production and utilisation of plan drawings of a model house. With one exception,
      results indicated that the LI children showed no deficit in ability on such
      tasks, and indeed out-performed their NLI peers on many of them. Implications of
      these findings are discussed.

PMID- 9279433
TI  - Are your minimal pairs too neat? The dangers of phonemicisation in phonology
      therapy.
AB  - Using Conversation Analysis (CA) to look at the interactional dynamics of therapy
      repair sequences, this paper shows exactly what happens for children when
      idealised misrepresentations of their phonology are used in therapy. The primary
      video extract involves a 4-year-old phonologically disordered boy and his
      therapist. It is not new to warn of the dangers of overlooking any subtle
      phonetic distinctions that the phonologically disordered child may have but this
      paper adds something new to the debate. The child's interpretation of the adult's
      prior turn in the sequence is made explicit and the likelihood of the child
      producing phonetic revision following an error is seen to be affected by the way
      the therapist chooses to initiate repair. This is especially true where a
      'redoing' of the error is incorporated into such an initiation, when the child's
      phonetic output is 'tidied up' so that it fits in with the neat minimal pair
      which forms part of the therapy programme. This is one factor that can be seen to
      militate against appropriate phonetic repair by the child, especially when used
      in certain turn structures that are routinely associated with lexical rather than
      phonetic matters. When the adult 'redoing' more accurately reflects the child's
      output phonetic revision is more likely to occur. Implications for assessment and
      therapy are drawn from this evidence, with accurate phonological assessment and
      continuing interactional error analysis being recommended.

PMID- 9279434
TI  - Understanding the potential of occupation: a qualitative exploration of seniors'
      perspectives on activity.
AB  - This article presents the results of a qualitative study that explored the
      characteristics and potential of occupation. Semistructured interviews with 12
      seniors who live in the community followed by member-checking groups were used to
      explore informants' perspectives on the importance and role of occupation in
      their lives by asking them about their activities. Themes pertinent to the
      characterization of activity, the contributions of activity, and a condition
      allowing for the potential of activity emerged from the inductive analysis. These
      themes provide information about how occupation naturally functions in the lives
      of seniors and suggest a tentative conceptualization of the characteristics and
      potential of occupation. The findings have implications for research regarding
      occupation and for clinical practice aimed at enabling occupation.

PMID- 9279435
TI  - Role perceptions of mothers with young children: the impact of a child's
      disability.
AB  - OBJECTIVE: The purpose of this study was to examine and compare the perceived
      past, present, and future occupational roles of mothers of young children.
      Awareness of the role demands placed on mothers will assist occupational
      therapists in addressing the needs of children with disabilities within the
      family context. METHOD: One hundred and thirty-five mothers of children 6 months
      to 5 years of age completed the Role Checklist, which examines participants'
      perceptions of past, present, and future occupational roles. Forty-five
      participants had children with multiple disabilities and major functional
      limitations, 45 had children with Down's syndrome, and 45 had children who were
      typically developing. RESULTS: The group of mothers of children who were
      typically developing was found to have significantly more present roles than the
      other two groups. All three groups lost significant numbers of roles from past
      (before birth of child) to present and anticipated adding significant numbers of
      future roles. There were no significant differences among the three groups in
      value placed on occupational roles. CONCLUSION: Role demands of caring for a
      young child were high for all participants, particularly if the child had a
      disability. Participants seemed to respond to these demands by giving up other
      discretionary roles in order to meet their caregiving obligations. Thus, asking
      mothers of children with disabilities to take on therapy-related caregiving tasks
      may contribute to role strain.

PMID- 9279436
TI  - "Doing" in mental health practice: therapists' beliefs about why it works.
AB  - OBJECTIVE: The purpose of this study was to explore the beliefs of occupational
      therapists working in mental health regarding the therapeutic value of "doing" as
      a treatment modality. Doing was defined as any activity or action-oriented
      approach that was identified and used by the participating therapists. METHOD:
      Eleven occupational therapists working in a variety of mental health areas were
      observed as they conducted 3 to 6 regularly scheduled therapy sessions. They were
      then interviewed about their activity-related beliefs. Audiotapes of the 44
      treatment sessions and 11 interviews were transcribed and then coded to identify
      emergent themes and categories of beliefs about activity. RESULTS: Participants
      used a variety of activities in both task-based and verbally based treatment
      sessions. Multiple reasons for activity use were cited, particularly in relation
      to the task-based sessions. Two main themes related to the value of activity were
      (a) benefits of activity for the client and (b) benefits in facilitating the
      process of therapy. Categories of client-related benefits included skill
      development; impairment reduction; self-awareness; positive self-concept;
      interaction or connection with others; healthy, balanced routines; pleasure; and
      enhancement of occupational role performance. Perceived effects on the
      therapeutic process included creating a therapeutic context, enhancing client
      readiness, facilitating communication, and providing an organizing framework.
      CONCLUSION: Occupational therapists working in mental health hold diverse beliefs
      about the value of doing in treatment. Basing practice on clearly identified and
      evidence-based beliefs will assist in ensuring a viable and valued future for the
      profession in this important domain of health services.

PMID- 9279437
TI  - An overview of professional liability in occupational therapy.
AB  - Occupational therapists occasionally are sued for professional malpractice; thus,
      they need to be aware of the law of malpractice, those areas of practice that
      present the greatest legal challenges, and strategies to reduce client injury and
      liability risks. This article provides an overview of the law of professional
      malpractice, explains the impact of various employment relationships on liability
      risks, reviews specific malpractice actions against occupational therapists, and
      provides suggestions on how to reduce the risk of injuring a client in therapy.
      By increasing one's awareness of the legalities of professional malpractice and
      implementing certain strategies, therapists can improve quality of care and
      reduce their exposure to malpractice liability.

PMID- 9279438
TI  - Skill acquisition and competency testing for physical agent modality use.
AB  - OBJECTIVE: The use of physical agent modalities is not considered an entry-level
      skill and requires postprofessional education, according to the American
      Occupational Therapy Association. The purpose of this survey was to determine how
      occupational therapy practitioners who use physical agents modalities are
      trained. METHOD: Two hundred fifty occupational therapists were randomly selected
      from the American Occupational Therapy Association's Physical Disabilities
      Special Interest Section. The practitioners were surveyed about their use of,
      education in, competency testing for, and opinions on eight physical agent
      modalities. RESULTS: Results were based on 100 responses (40% response rate). Of
      the eight modalities, the most commonly used were hot and cold packs, and the
      least were transcutaneous electrical nerve stimulators. The most common means of
      education was on-the-job training, and the least common was higher level
      accredited education. A majority (71) of respondents reported that no competency
      testing was being performed at their facilities. In the remaining facilities
      (29), the majority performed competency tests with no routine frequency, using no
      particular guidelines for testing and no formal methods for maintaining standards
      for physical agent modality use. Eighty-five respondents indicated they would be
      interested in attending continuing education programs on the use of physical
      agent modalities, and 88 believed that functional activities should follow the
      use of physical agent modalities within the same treatment session. CONCLUSION:
      The occupational therapy profession may need specific educational and competency
      guidelines to assure the qualifications of therapists using physical agent
      modalities.

PMID- 9279439
TI  - Understanding professional behavior: experiences of occupational therapy students
      in mental health settings.
AB  - A phenomenological study explored occupational therapy students' experiences in
      psychiatric fieldwork. Of particular interest was students' understanding of
      professional behavior toward persons who use mental health services. Data were
      gathered from 16 informants via in-depth interviews and participant observation
      on multiple occasions during fieldwork affiliations. Emerging from informants'
      views of professional behavior were difficulties in their reconciling conflicting
      expectations with regard to emotional and social distance from persons who use
      mental health services. Additionally, the informants experienced a need to assume
      authority and maintain control in their dealings with service users. Students'
      encounters with such issues during fieldwork are indicative of challenges they
      may face as health professionals in a changing climate of mental health services.
      These data are stimuli for reflection on features of professional relationships
      with service users, particularly in response to expectations of persons with
      disabilities regarding control over their lives.

PMID- 9279440
TI  - Clinical interpretation of "understanding professional behavior: experiences of
      occupational therapy students in mental health settings".

PMID- 9279441
TI  - Work-related post-traumatic stress disorder: use of exposure therapy in work
      simulation activities.

PMID- 9279442
TI  - Ergonomics in health care.

PMID- 9279443
TI  - Applied scientific inquiry: an answer to managed care's challenge?

PMID- 9279444
TI  - Criticism of Fidler's model debated.

PMID- 9279445
TI  - Cancers of the salivary gland: workplace risks among women and men.
AB  - PURPOSE: The purpose of this study was to assess the risk of salivary gland
      cancers associated with diverse occupations and industries. METHODS: A population
      based case referent study utilized data obtained from a SEER program cancer
      registry for cases and by telephone interview for cases and referents to evaluate
      workplace risks of salivary gland cancer for black and white women and men.
      RESULTS: Significantly elevated odds ratios were observed among women employed as
      hairdressers and those working in beauty shops. CONCLUSIONS: The risk of salivary
      gland cancer is elevated among women employed as hairdressers. Further research
      should assess dyes, sprays, and other inhaled chemicals that may be acting as
      carcinogens.

PMID- 9279446
TI  - Risk factors, lifetime risk, and age at onset of breast cancer.
AB  - PURPOSE: We evaluated the relationship between exposure variables and both
      lifetime risk and mean age at diagnosis of breast cancer in subjects from the
      Adventist Health Study who developed breast cancer before the age of 91 years.
      METHODS: Multiple decrement life-table analysis was used. This study provided
      data from 20,341 women followed for 6 years. RESULTS: In the total population, 30
      year-old women with a parental history of any cancer or a maternal history of
      breast cancer had, respectively, 72% (P < 0.002) and 98% (P < 0.03) higher
      lifetime risks of breast cancer. Thirty-year-old women who had their first
      delivery after age 24 years or body mass indices above the 50th percentile had,
      respectively, 53% (P < 0.007) or 57% (P = 0.01) greater lifetime risk of breast
      cancer. Women who exercised infrequently had a 27% higher life-time risk (P =
      0.09) and an age at diagnosis of breast cancer 6.6 years younger (P < 0.005) than
      other women. CONCLUSIONS: Standard risk factors account for substantial increases
      in lifetime risk of breast cancer and may be associated with differences in age
      at diagnosis.

PMID- 9279447
TI  - Relative weight and mortality in U.S. blacks and whites: findings from
      representative national population samples.
AB  - PURPOSE: To examine the impact of relative weight on mortality in black and white
      men and women. METHODS: Two representative national populations samples were
      used: the NHANES-I Epidemiologic Follow-up Study (NHEFS), and the National Health
      Interview Survey (NHIS). The principal analysis focused on 13,242 participants in
      the NHEFS and 114,954 in the NHIS. Minimum mortality was estimated from both
      categorical analysis and a logistic model. RESULTS: Minimum mortality ranged from
      a body mass index (BMI) of 25 to 32 kg/m2. The model-estimated BMI of minimum
      mortality for NHEFS was 27.1 (24.8-29.4, 95% CI), 26.8 (24.7-28.9, 95% CI), 24.8
      (23.8-25.9, 95% CI) and 24.3 (23.2-25.4, 95% CI); for black men, black women,
      white men and white women, respectively, whereas for NHIS the corresponding
      values were 30.2 (24.8-35.6, 95% CI) 26.4 (24.2-28.7, 95% CI), 27.1 (25.5-28.7,
      95% CI), and 25.6 (24.2-27.0, 95% CI). In all groups the shape of the relative
      risk curve was virtually identical and a broad range of BMI values in the middle
      of the distribution was associated with low relative mortality risk. Averaging
      the results from both surveys, the observed BMI of minimum risk was 3.1 kg/m2
      higher in black men and 1.5 kg/m2 higher in black women than in their white
      counterparts; when adjusted for covariates these differences were only of
      borderline statistical significance, however. CONCLUSIONS: Because of the wide
      range of BMI values associated with low risk, and the consistency of the point of
      the up-turn in risk, group specific definitions of optimal values do not appear
      to be warranted.

PMID- 9279448
TI  - Reliability of proxy reports of parental smoking by elementary schoolchildren.
AB  - PURPOSE: To investigate the reliability of reports of parental smoking by
      elementary schoolchildren aged 9-13 years, and to identify the correlates of
      disagreement between student proxy and parent self-reports. METHODS: As part of
      the evaluation of a school-based heart health promotion program, data on parental
      smoking status were collected from 1240 student-mother pairs and 898 student
      father pairs. RESULTS: Agreement for parental smoking status was 93.1% among
      student-mother pairs and 86.4% among student-father pairs. Among student-mother
      pairs, reports by students aged 9 years were more likely to disagree with
      mothers' self-reports than those of older children (odds ratio (OR) = 3.1). Among
      student-father pairs, the only significant correlate of disagreement was living
      in a single-parent family headed by the mother (OR = 2.6). CONCLUSIONS: Children
      10-years or older can provide reliable reports of the smoking status of
      cohabiting parents.

PMID- 9279449
TI  - Young maternal age and preterm labor.
AB  - PURPOSE: The relationship among young age, biologic immaturity (as indexed by low
      gynecologic age), and the causes of preterm delivery (idiopathic preterm labor
      [PTL], premature rupture of the membranes [PROM], and medical indications) were
      investigated among 605 primigravidas from the Camden Study. METHODS: The sample
      consisted of 366 young adolescents < 16 years at the time of their last menstrual
      period (LMP) and 239 older women, 18-29 years at LMP (controls). The young
      adolescents were significantly shorter, thinner, had younger ages at menarche,
      and over a third (36.3%) were of low gynecologic age, i.e., their chronologic age
      was 2 or fewer years more than their age at menarche. RESULTS: Adjusting for
      ethnicity, cigarettes smoked/day, weight gain rate, height, fetal sex,
      gestational diabetes mellitus, and pregnancy-induced hypertension, young
      adolescents overall had a nearly 75% increased risk of PTL (adjusted odds ratio
      [AOR] = 1.74, 95% confidence interval [95% CI]: 1.07-2.84), and preterm delivery
      with PTL (AOR = 2.08, 95% CI: 1.08-4.00). There was a modest decreased risk of
      preterm delivery among young gravidas attributable to other causes, such as PROM
      or medical indications (AOR = 0.70, 95% CI: 0.28-1.75). This increased risk of
      PTL and preterm delivery with PTL was principally attributable to biologic
      immaturity. Young age with low gynecologic age was associated with a twofold risk
      of PTL (AOR = 2.15, 95% CI: 1.19-3.89) and preterm delivery with PTL (AOR = 2.64,
      95% CI: 1.23-5.65), while the risk associated with young age and higher
      gynecologic age was only increased moderately. CONCLUSIONS: Young adolescents,
      and especially those of low gynecologic age, appear prone to PTL and are at
      increased risk for preterm delivery through this pathway.

PMID- 9279451
TI  - Cross-sectional and longitudinal changes in total and high-density-lipoprotein
      cholesterol levels over a 20-year period in elderly men: the Honolulu Heart
      Program.
AB  - PURPOSE: The purpose of this report is to describe levels of total cholesterol
      and high-density-lipoprotein cholesterol (HDL-C) in a group of elderly men and to
      compare these levels to those that were observed 20 years earlier. METHODS: From
      1965-1968, the Honolulu Heart Program began following 8006 men of Japanese
      ancestry living on the island of Oahu, Hawaii, in a prospective study of coronary
      heart disease and stroke. This report presents data for 971 men who participated
      in a separate fasting study of lipids and lipoproteins that first occurred from
      1970-1972 and in those who received repeat examinations 10 and 20 years later.
      Men were aged 71-93 years at the last examination. RESULTS: Over the 20-year
      period, total cholesterol declined by 1.6-1.8 mg/dL per year (P < 0.001), from
      average baseline values of 219-222 mg/dL. Levels of HDL-C rose 0.2-0.3 mg/dL per
      year (P < 0.001), from average baseline values of 44-46 mg/dL. After adjustment
      for baseline cholesterol levels, men with prevalent coronary heart disease at the
      end of the 20-year follow-up experienced significantly greater reductions in
      total cholesterol levels than men without disease (P < 0.001). Men who developed
      coronary heart disease within the first 10 years of follow-up had the greatest
      yearly decline in total cholesterol (1.9 mg/dL), followed by men who developed
      heart disease later (1.8 mg/dL) and men who remained disease free (1.5 mg/dL).
      Differences between men with recent and earlier disease were not statistically
      significant, although men without coronary disease experienced a significantly
      smaller decrease in total cholesterol than either of these groups (P < 0.05).
      CONCLUSIONS: Changes in total cholesterol and HDL-C levels with advancing age may
      be part of a natural aging process. Some changes, however, such as large
      reductions in total cholesterol, may signal occult disease or declines in overall
      health. Selective survival may contribute to these findings since improvements in
      lipid and lipoprotein levels that are beneficial in younger ages were common in
      this long-lived cohort of men.

PMID- 9279450
TI  - Development of the multiple metabolic syndrome in the ARIC cohort: joint
      contribution of insulin, BMI, and WHR. Atherosclerosis risk in communities.
AB  - PURPOSE: The natural history of the multiple metabolic syndrome (MMS) and its
      predictors has rarely been addressed in population samples. This study evaluated
      the predictive role of fasting serum insulin, body mass index (BMI), and waist-to
      hip ratio (WHR) on the development of incident MMS components (diabetes,
      hypertension, and dyslipidemias) over the course of three years. METHODS: The
      study population comprised the cohort of middle-aged African American and
      European American men and women of the Atherosclerosis Risk in Communities Study
      (1987-1992). RESULTS: Among 6113 individuals free of MMS components at baseline,
      high insulin (> 14 microU/ ml) was independently predictive of the development of
      one or more MMS components (OR:1.5, 95% CI:1.2-1.8), as was a BMI > or = 30
      (OR:1.7, 95% CI:1.4-2.0), and a high WHR (> 0.98) (OR:1.5, 95% CI:1.3-1.8)
      adjusting statistically for age, gender, and ethnicity/center. These associations
      were markedly stronger for combinations of MMS components (two or more) than for
      isolated components. CONCLUSIONS: The findings confirm earlier reports on the
      predictive role of insulin, BMI, and WHR, and suggest that these antecedent
      factors may be integral to the development of combinations of disorders, i.e.,
      the particular clustering identified as the MMS.

PMID- 9279452
TI  - Methylergonovine maleate and risk of breast cancer.

PMID- 9279453
TI  - Geographic trends in prostate cancer mortality: an application of spatial
      smoothers and the need for adjustment.

PMID- 9279454
TI  - Cytomechanics of axonal development.
AB  - Mechanical tension is a robust regulator of axonal development of cultured
      neurons. We review work from our laboratory, using calibrated glass needles to
      measure or apply tension to chick sensory neurons, chick forebrain neurons, and
      rat PC12 cells. We survey direct evidence for two different regimes of tension
      effects on neurons, a fluid-like growth regime, and a nongrowth, elastic regime.
      Above a minimum tension threshold, we observe growth effects of tension
      regulating four phases of axonal development: 1. Initiation of process outgrowth
      from the cell body; 2. Growth cone-mediated elongation of the axon; 3. Elongation
      of the axon after synaptogenesis, which normally accommodates the skeletal growth
      of vertebrates; and 4. Axonal elimination by retraction. Significantly, the
      quantitative relationship between the force and the growth response is
      surprisingly similar to the simple relationship characteristic of Newtonian fluid
      mechanical elements: elongation rate is directly proportional to tension (above
      the threshold), and this robust linear relationship extends from physiological
      growth rates to far-above-physiological rates. Thus, tension apparently
      integrates the complex biochemistry of axonal elongation, including cytoskeletal
      and membrane dynamics, to produce a simple "force input/growth output"
      relationship. In addition to this fluid-like growth response, peripheral neurons
      show elastic behaviors at low tensions (below the threshold tension for growth),
      as do most cell types. Thus, neurites could exert small static forces without
      diminution for long periods. In addition, axons of peripheral neurons can
      actively generate modest tensions, presumably similar to muscle contraction, at
      tensions near zero. The elastic and force-generating capability of neural axons
      has recently been proposed to play a major role in the morphogenesis of the
      brain.

PMID- 9279455
TI  - Regulation of cellular thiol redox status by nitric oxide.
AB  - Nitric oxide (NO) is an important biological molecule that participates in a wide
      range of responses, including vasodilation, platelet regulation,
      neurotransmission, and cytoxicity. NO's most widely known and best understood
      mechanism of action is through its interaction with the heme group in proteins
      such as soluble guanylate cyclase. In addition to heme iron, NO has also been
      shown to react with other functional groups in proteins. However, it is becoming
      clear that many reactions previously attributed to NO are now known to be
      mediated through NO-derived species (NOx) and not directly through NO itself (as
      discussed below). The thiol group of cysteine residues represents one potential
      target of NOx and may be of particular biological relevance since cysteines are
      important for maintaining the native conformation of proteins, are critical to
      the activity of many enzymes, and are the most reactive amino acid residues at
      physiological pH. In fact, modification of protein thiols by NOx alters the
      function and activity of various proteins including enzymes, signaling proteins,
      ion channels, receptors, transcription factors, and antioxidants. These
      alterations in protein function, through modification of thiols, may be critical
      for initiating signaling events or may be detrimental to the cell by disrupting
      essential protein function. This article aims to review the interactions of NOx
      with protein and nonprotein thiols, including mechanisms of thiol modification,
      reversibility of NOx-mediated protein thiol modification, and cellular defense
      mechanisms involved in regulating NOx-mediated modification of protein thiols.

PMID- 9279456
TI  - Cell-cell and cell-ECM interactions in epithelial apoptosis and cell renewal
      during frog intestinal development.
AB  - Amphibian intestinal remodeling during metamorphosis is a developmental system
      that is entirely controlled by thyroid hormone. It transforms a simple tubular
      organ into a complex multiply folded frog intestine similar to that in higher
      vertebrates. This process involves the degeneration of the larval epithelium
      through programmed cell death (apoptosis) and concurrent proliferation and
      differentiation of adult cell types. Earlier morphological and cellular studies
      have provided strong evidence implicating the importance of cell-cell and cell
      ECM (extracellular matrix) interactions in this process. The recent molecular
      characterization of the genes that are regulated by thyroid hormone has begun to
      reveal some molecular clues underlying such interactions. In particular, the
      Xenopus putative morphogen hedgehog appears to be involved in
      regulating/mediating cell-cell interactions during adult epithelial
      proliferation, differentiation, and/or intestinal morphogenesis. On the other
      hand, several matrix metalloproteinases (MMPs) may be involved in remodeling the
      ECM. Of special interest is stromelysin-3, whose spatial and temporal expression
      profile during intestinal metamorphosis implicates a role in ECM remodeling,
      which in turn facilitates cell fate determination, i.e., apoptosis vs
      proliferation and differentiation. Understanding the mechanisms of action for
      those extracellular molecules will present a future challenge in developmental
      research.

PMID- 9279458
TI  - On the role of a mutational database in building artificial intelligence models
      for understanding gene expression.

PMID- 9279457
TI  - Coordinated effects of electromagnetic field exposure on erythropoietin-induced
      activities of phosphatidylinositol-phospholipase C and phosphatidylinositol 3
      kinase.
AB  - Initial studies with the erythropoietin-sensitive human hematopoietic cell line,
      TF1, demonstrated both multifarious effects of pulsed electromagnetic field (EMF)
      exposure on lipid signal transduction and antiproliferative effects of EMF.
      Stimulation of TF1 cells with erythropoietin resulted in increased
      phosphatidylinositol 3-kinase activity within 2 min. Addition of wortmannin, an
      inhibitor of phosphatidylinositol 3-kinase, produced a decrease in cell
      proliferation as measured by accumulation of cells in the G0/G1 phase of the cell
      cycle and suppression of erythropoietin-induced DNA synthesis. Similar effects on
      cell proliferation were seen under EMF treatment. Phosphatidylinositol 3-kinase
      activity in erythropoietin-stimulated TF1 cells, measured in whole-cell extracts,
      increased 34% within 2 min and remained above basal levels for at least 20 min.
      EMF decreased erythropoietin-stimulated phosphatidylinositol 3-kinase activity to
      lower than basal levels. Additionally, translocation of the 85-kDa regulatory
      subunit (p85) of phosphatidylinositol 3-kinase to the membrane was prevented by
      EMF. Phosphatidylinositol-specific phospholipase C was activated, as reflected by
      increases in diacylglycerol and inositol trisphosphate at 15-60 s after EMF
      treatment. These results provide the first evidence of subtle coordinated changes
      by EMF associated with loss of phosphatidylinositol 3-kinase activity, inhibition
      of the translocation of p85 to the membrane, and activation of
      phosphatidylinositol-phospholipase C.

PMID- 9279459
TI  - Sensitivity of rat cortical neurons in distinguishing taste qualities by
      individual and correlative activities.
AB  - To examine the possibility that different taste qualities are represented by the
      correlative activity of cortical gustatory neurons, we made simultaneous
      recordings of neuron pairs during application of four basic tastes into the oral
      cavity of anesthetized rats and the following observations were made: (i) in 30
      of 67 pairs of taste responsive neurons, peaks (troughs in a few cases) were
      produced in the cross-correlograms (CCs) during stimulation with some tastants;
      (ii) the correlative discharges occupied 6-8% of the total spikes discharged by
      individual neurons during taste stimulation and occurred, in a considerable
      number of cases, even during stimulation with tastants to which one or both of
      the component neurons of a pair were apparently non-responding (often sucrose and
      quinine); (iii) the number of tastants to which a neuron pair responded with a
      significant correlative activity was often greater than the number of tastants to
      which the component neurons of the same pair responded with significant changes
      in discharge rate; (iv) there was no significant difference between the
      correlative (formation of peaks or troughs in the CC) and individual (change in
      discharge rate of individual neurons) ways of coding in the sensitivity to
      distinguish between two taste qualities ranked to be adjacent on the basis of the
      number of spikes composing the response; and (v) the peaks or troughs appearing
      in two CCs during stimulations with two kinds of tastants were compared with
      regard to overlapping of their delay ranges and widths. The spikes in the non
      overlapping portion of each peak (suppressed spike number in the case of troughs)
      are supposed to be able to contribute to two-taste discrimination: the correlated
      discharges occurring with a delay time that corresponds to the overlapping
      portion can in no way be judged differently, but the spikes falling in the non
      overlapping portion may contribute to the differentiation. The ratio of the non
      overlapping portion to the entire peak (or trough) was 0.35 on average. It is
      concluded that temporal coding of taste qualities seems to operate effectively in
      the gustatory cortex.

PMID- 9279460
TI  - Visual and chemical release of feeding behavior in adult rainbow trout.
AB  - Feeding behavior of adult rainbow trout (Oncorhynchus mykiss) is released by
      visual and/or chemical stimuli. Detection of either a conditioned visual or a
      conditioned chemical stimulus creates an excitatory feeding state within the
      central nervous system which turns on feeding behavior composed of swimming,
      turning and biting/snapping actions. Particular amino acids that are highly
      effective physiological taste stimuli that are also detected through olfaction
      (e.g. L-proline, L-alanine, L-leucine) release the initial sequence of food
      searching and biting/snapping behaviors; however, an effective olfactory, but
      poor gustatory, stimulus (e.g. L-arginine) is rarely effective behaviorally.
      After bilateral removal of the paired olfactory organs, visual stimuli alone
      release the entire set of feeding behavior patterns. Since amino acids that are
      highly potent physiological taste stimuli do not release either feeding behavior
      or reflex biting/snapping actions in adult anosmic rainbow trout, it is
      postulated that the olfactory system detects potent taste stimuli and provides
      the afferent input for arousal and the release of all feeding activity patterns.

PMID- 9279461
TI  - Three odorant-binding proteins from rabbit nasal mucosa.
AB  - Following the purification of an odorant-binding protein (OBP) from rabbit nasal
      mucosa, we have identified, purified and partially characterized two additional
      OBPs from the nasal tissue of the same animal species. OBP-II is a monomer of 21
      kDa and isoelectric point 4.2; OBP-III is a dimer with subunits of 23 kDa and
      isoelectric point 4.8. Like OBP-I, both these new members bind the odorant 2
      isobutyl-3-methoxypyrazine. The partial amino acid sequences of the three OBPs,
      determined by Edman degradation, confirm that they are members of the OBP family,
      but reveal poor similarity between them. However, higher similarity is found
      between each OBP and other members of the lipocalin family. In particular, OBP-I
      is most similar to bovine OBP (55% identity in the N-terminal region), OBP-II is
      > 50% identical, limited to its first 18 amino acids, to mouse OBP-I and
      porcupine OBP-II, while OBP-III shares 26 out of the first 40 amino acids with
      major urinary protein (MUP) 4, a member of the mouse salivary proteins. The
      possible role of these proteins in olfactory transduction is also discussed.

PMID- 9279462
TI  - Effect of conditioning on discrimination of oilseed rape volatiles by the
      honeybee: use of a combined gas chromatography-proboscis extension behavioural
      assay.
AB  - The coupled gas chromatography-proboscis extension assay technique was used on
      restrained worker bees to study responses to components of an extract of oilseed
      rape floral volatiles. Bees were stimulated with the effluent from the gas
      chromatograph after either paired or unpaired conditioning to the extract, or
      after a control treatment. Proboscis extension activity was elicited in six areas
      of the chromatogram. However, the number of bees responding in two of these areas
      were too low to be considered in the present study. One significant area of
      activity was associated with the major component, (E,E)-alpha-farnesene, whilst
      the others were associated with several minor components. Although all three
      groups of bees, irrespective of the treatments applied, showed some responses to
      the components eluting from the GC column, only bees subjected to paired
      conditioning consistently responded when re-tested to the mixture. In addition,
      paired conditioning increased the responsiveness of individuals in terms of the
      number of bees responding at least once to the effluent from the gas
      chromatograph. This work confirmed the occurrence of key compounds in floral
      volatile mixtures. Possible synergistic/inhibitory effects between components,
      relating to olfactory experience, are discussed.

PMID- 9279463
TI  - Convergence of oropharyngolaryngeal, baroreceptor and chemoreceptor afferents
      onto insular cortex neurons in rats.
AB  - Forty-two neurons that responded to electrical stimulation of at least one of
      four nerves, the chorda tympani (CT), the lingual-tonsillar branch of the
      glossopharyngeal (LT-IXth) nerve, the pharyngeal branch of the glossopharyngeal
      (PH-IXth) nerve and the superior laryngeal (SL) nerve, were identified from the
      insular cortex by using glass microelectrodes in paralysed and anesthetized rats.
      Four, 42, 41 and 40 neurons responded to the CT, LT-IXth, PH-IXth and SL nerve
      stimulation respectively. Of these 42 neurons, most (37/42, 88.1%) responded to
      three nerves (the LT-IXth, PH-IXth and SL), two (4.8%) responded to two nerves
      and the remaining three (7.1%) responded to all four nerves. No neurons responded
      to one specific stimulus. The responsiveness of these 42 neurons to baroreceptor
      and chemoreceptor stimulation by an i.v. injection of three drugs was
      investigated. For baroreceptor stimulation, methoxamine hydrochloride (Mex) and
      sodium nitroprusside (SNP) were used; for chemoreceptor stimulation, sodium
      cyanide (NaCN) was used. Of the 42 neurons, 31 (73.8%) showed an excitatory or
      inhibitory response to baroreceptor and chemoreceptor stimulation with at least
      one of the three drugs, and the remaining 11 (26.2%) showed no response. Of these
      31 baroreceptor and chemoreceptor-sensitive neurons, 19 (61.3%) responded to two
      or all three drugs, and the rest (12; 38.7%) responded to one. Most neurons
      recorded were distributed in the posterior insular cortex. These results indicate
      that the neurons in the posterior insular cortex receive convergent inputs from
      the oropharyngolaryngeal region, the baroreceptors and the chemoreceptors,
      suggesting that the posterior insular cortex may integrate various sensory
      information.

PMID- 9279464
TI  - Effects of trifluoromethyl ketones and related compounds on the EAG and
      behavioural responses to pheromones in male moths.
AB  - Trifluoromethyl ketones (TFMKs) and analogues affect pheromone detection and
      behaviour in male moths. 3-Octylthio-1,1,1-trifluoropropan-2-one (OTFP), one of
      the most effective antiesterase agents, decreased the EAG amplitude and increased
      the repolarization time in Spodoptera littoralis. It also modified EAG responses
      of Mamestra brassicae and Heliothis zea to their pheromones and analogues,
      containing an acetate, an alcohol or an aldehyde function. In addition, OTFP also
      reduced the amplitude of the EAG response to linalool, a monoterpenic alcohol,
      but not its kinetics. The responses of male S. littoralis to the pheromone in the
      wind tunnel were significantly reduced after pre-exposure to vapours of OTFP.
      Comparison of the activity of other TFMKs and analogues with that of OTFP
      revealed a good agreement on EAG and behaviour. The effects of TFMKs on the EAG
      kinetics are discussed considering the hypothesis of an inhibition of the
      pheromone deactivation in the antenna.

PMID- 9279465
TI  - Purification, identification, concentration and bioactivity of (Z)-7-dodecen-1-yl
      acetate: sex pheromone of the female Asian elephant, Elephas maximus.
AB  - In their natural ecosystems, adult male and female Asian elephants, Elephas
      maximus, live separately. For several weeks prior to ovulation, female elephants
      release a substance in their urine which elicits a high frequency of non
      habituating chemosensory responses, especially flehmen responses, from male
      elephants. These responses occur prior to, and are an integral part of, mating.
      Using bioassay-guided fractionation, quantitatively dependent on these
      chemosensory responses, a specific sex pheromone was isolated and purified by an
      alternating series of organic and/or aqueous extractions, column chromatography,
      gas chromatography and high-performance liquid chromatography. Using primarily 1H
      proton nuclear magnetic resonance (NMR) spectrometry and gas chromatography-mass
      spectrometry (GC-MS) of the urine-derived pheromone and its dimethyl disulfide
      derivative, we determined the structure of the active compound to be (Z)-7
      dodecen-1-yl acetate (Z7-12:Ac). Concentrations of Z7-12:Ac in the female urine
      increased from non-detectable during the luteal phase to 0.48 microgram/ml (0.002
      mM) early in the follicular phase and to 33.0 micrograms/ml (0.146 mM) just prior
      to ovulation. Bioassays with commercially available authentic synthetic Z7-12:Ac,
      using 10 Asian male elephants at several locations in the US, demonstrated
      quantitatively elevated chemosensory responses that were robust during successive
      tests, and several mating-associated behaviors. Bioassays with Z7-12:Ac with
      adult male elephants dwelling in more natural social situations in forest camps
      in Myanmar revealed some differing contextual pre-mating behavioral components.
      The remarkable convergent evolution of this compound suggests that compounds
      identified in mammalian exudates that are also present in pheromone blends of
      insects should be re-evaluated as potential mammalian chemosignals.

PMID- 9279466
TI  - Biogenic amines in the vomeronasal organ.
AB  - The vomeronasal organ of frog and mouse was investigated for the presence and
      content of serotonin and catecholamines by means of high-performance liquid
      chromatography. Measurable amounts of serotonin, adrenaline and noradrenaline
      were found in the vomeronasal organ of adult individuals of both species. The
      amine content varied with sex of adult frogs and mice and sexual maturity of
      mice. In preliminary experiments, acute exposure to male urine containing
      pheromone affected the amine content in the vomeronasal organ of adult female
      mice. These data suggest that functional sex dimorphism is present in the
      vomeronasal organ, and biochemical changes therein take place according to stage
      of sexual maturity. The role of biogenic amines in the vomeronasal organ deserves
      further study.

PMID- 9279467
TI  - Trigeminal perception of odorant quality in congenitally anosmic subjects.
AB  - Twenty congenitally anosmic subjects and 50 normosmic controls were tested for
      their ability (i) to assign verbal labels from a list of trigeminal-type
      descriptors to six odorants believed to have a strong trigeminal component; and
      (ii) to discriminate between intensity-matched pairs of these odorants in an odd
      ball paradigm. The following was found: normosmic controls judged menthol and
      cineole as distinctly cool and fresh, acetic acid as pungent and sour, and
      acetone as pungent, but showed no clear descriptive profile for ethanol and
      propanol. The descriptive profiles given by the anosmic subjects correlated
      significantly with those given by the controls for three of the six odorants
      (menthol, cineol and ethanol), confirming that the sensations described may
      indeed be mediated by the trigeminal system. In the odd-ball test, the control
      subjects correctly identified an average of eight out of the nine items
      presented, with most mistakes occurring in response to pairs with a similar
      trigeminal profile. With an average of 7.2 of nine items correct, the performance
      of the anosmic subjects was not significantly different to that of the
      normosmics, except in discriminating between acetic acid and menthol. Although
      additional tests are necessary to decide finally whether differences in stimulus
      intensity may have contributed to this good discriminatory performance, the
      present results suggest that the nasal trigeminal system may contribute
      significantly to the perception of odor quality.

PMID- 9279468
TI  - Olfactory discrimination ability for aliphatic esters in squirrel monkeys and
      humans.
AB  - Using a behavioral paradigm designed to simulate olfactory-guided foraging, the
      ability of five squirrel monkeys to distinguish iso-amyl acetate from n- and iso
      forms of other acetic esters (ethyl acetate to decyl acetate) and from other
      esters carrying the iso-amyl group (iso-amyl propionate to iso-amyl capronate)
      was investigated. We found (i) that all five animals were clearly able to
      discriminate between all odor pairs tested; (ii) a significant negative
      correlation between discrimination performance and structural similarity of
      odorants in terms of differences in carbon chain length of both the aliphatic
      alcohol group and the aliphatic acid group of the esters; and (iii) that iso- and
      n-amyl acetate were perceived as qualitatively similar despite different steric
      conformation. Using a triple-forced choice procedure, 20 human subjects were
      tested on the same tasks in parallel and showed a very similar pattern of
      discrimination performance compared with the squirrel monkeys. Thus, the results
      of this study provide evidence of well-developed olfactory discrimination ability
      in squirrel monkeys for aliphatic esters and support the assumption that human
      and non-human primates may share common principles of odor quality perception.

PMID- 9279469
TI  - Functional expression of odorant receptors of the zebrafish Danio rerio and of
      the nematode C. elegans in HEK293 cells.
AB  - Odorant receptors of zebrafish and C elegans were functionally expressed in
      vertebrate kidney cells (HEK293) using the eucaryotic expression vector pSMyc.
      Receptor-encoding cDNA cloned into this vector was expressed as a fusion protein
      with the N-terminal membrane import sequence of the guinea-pig serotonin receptor
      followed by a myc tag. Immunocytochemical evidence indicates that this strategy
      directs a protein with the predicted immunoreactivity and approximate molecular
      weight to the plasma membrane. Fish food extract (TetraMin) evoked a transient
      increase in intracellular [Ca2+] in HEK293 cells transiently transfected with
      plasmids containing cDNA for three fish odorant receptors and converted to stable
      cell lines. The effect of the extract was concentration dependent and limited to
      the fraction of the extract < 5 kDa. Pretreating the transfected cells with the
      PLC inhibitor U73122 reduced the odor-evoked signal. Fish food extract also
      evoked a transient increase in intracellular [Ca2+] in HEK293 cells transiently
      transfected with plasmids containing cDNA for single fish odorant receptors.
      Diacetyl evoked a transient increase in intracellular [Ca2+] in HEK293 cells
      transiently transfected with plasmids encoding the cDNA of ODR10, an odorant
      receptor of C. elegans suggested in other work to be specific for diacetyl. These
      results strongly imply that odorant receptors can be functionally expressed in
      HEK293 cells using this novel expression protocol.

PMID- 9279470
TI  - Bimodal (taste/tactile) fibers innervate the maxillary barbel in the channel
      catfish.
AB  - Analysis of single fibers isolated from a branch of the facial/trigeminal complex
      innervating the maxillary barbel of the channel catfish, Ictalurus punctatus,
      indicated the existence of bimodal (taste/tactile) fibers. Of the 60 single
      fibers recorded, 14 (23%) responded to both taste (amino acid) and tactile
      stimulation, 43 (72%) were responsive to only tactile stimulation and three (5%)
      responded only to taste stimulation. Quinine hydrochloride at a concentration of
      > or = 1.0 mM suppressed the mechanosensory activity of the bimodal fibers, but
      had no effect on the tactile-only fibers.

PMID- 9279471
TI  - Beta 3-adrenergic receptor gene polymorphism is not a major genetic determinant
      of obesity and diabetes in Japanese general population.
AB  - To assess the contribution of a replacement of Trp at codon 64 of beta 3
      adrenergic receptor by Arg to fat distribution and metabolic disturbances in
      Japanese general population, we examined the missense mutation in 1122 persons
      consisting of 817 men aged 50.0 +/- 8.9 years and 305 women aged 50.8 +/- 8.5
      years in Kyushu, Japan. The incidence of Arg64 allele was 0.21; no age-dependent
      decrease of the allele frequency was observed, suggesting that the mutation was
      not associated with early mortality. The genotype was not significantly
      correlated with body mass index or the thickness of visceral fat estimated by
      ultrasonography. Glucose tolerance and glucose-induced insulin secretion were not
      significantly different among subjects with Trp/Trp, Trp/Arg and Arg/Arg at codon
      64. Although in obese persons the ratio of heterozygotes for the mutation tended
      to be higher in subjects with impaired glucose tolerance than in subjects with
      normal glucose tolerance, the tendency was not observed in non-obese persons.
      Furthermore none of 39 non-obese individuals homozygous for the mutation was
      diabetic, whereas two out of six obese homozygous persons were diabetic. These
      observations suggest that the missense mutation may not be a main determinant of
      obesity in populations taking low fat/low energy Japanese-style diet and it may
      not be deleterious at least in non-obese individuals.

PMID- 9279472
TI  - Failure of high-dose insulin treatment to increase beta-cell insulin content in
      diabetic non obese diabetic (NOD) mice.
AB  - High-dose insulin treatment in the first period after clinical onset of insulin
      dependent diabetes mellitus (IDDM) has been found to reduce diabetic
      manifestations in humans. The aim of the present study was to examine whether
      high-dose insulin treatment of newly diagnosed diabetic non obese diabetic (NOD)
      mice would increase beta-cell insulin content after termination of treatment in
      this experimental IDDM animal model. Newly diagnosed diabetic female NOD mice
      were randomized into three groups composed of a low-dose insulin treated group (n
      = 10) injected subcutaneously with 15 IU/kg per day of NPH for 14 days followed
      by 5 days without insulin, a high-dose insulin treated group (n = 8) injected
      subcutaneously with 150 IU/kg per day of Actrapid for 14 days followed by 5 days
      without insulin and an untreated group sacrificed 3 days after diagnosis (n =
      11). A reference group of age matched non-diabetic untreated female NOD mice (n =
      11) was included in the study and sacrificed at the same time as the untreated
      diabetic mice. No significant difference in the amount of insulin extracted from
      the total pancreas was found by comparison of the three diabetic groups,
      consisting of the newly diagnosed untreated mice, the low-dose insulin treated
      mice and the high-dose insulin treated mice, respectively. The level was about
      100-fold less than in the non-diabetic group. Blood glucose values in the two
      treated diabetic groups were at a high level (median > 18 mM) throughout the
      study. We conclude that no increase in beta-cell insulin content could be
      demonstrated in newly diagnosed diabetic NOD mice after early high-dose insulin
      treatment, at least not in the presence of high blood glucose values.

PMID- 9279473
TI  - Raised erythrocyte polyamine levels in non-insulin-dependent diabetes mellitus
      with great vessel disease and albuminuria.
AB  - Erythrocyte content of polyamines has been previously found increased in insulin
      dependent diabetes mellitus with microalbuminuria. Since increased urinary
      albumin excretion (AER) is associated with the presence of vascular diseases in
      non-insulin-dependent diabetes mellitus (NIDDM) the aim of this study was to
      verify the hypothesis that the presence of increased urinary albumin excretion
      (AER), and of macroangiopathy in NIDDM would be related to a significant
      modification in polyamine erythrocyte levels. The erythrocyte content of spermine
      and spermidine was measured by a HPLC method in 39 patients affected with NIDDM
      and in 24 age- and sex-matched healthy control subjects, evaluating the
      relationship between erythrocyte polyamines of NIDDM patients with the presence
      of macroangiopathy as well as with retinopathy or increased AER (> or = 20
      micrograms/ml). Both spermidine and spermine were not modified in the group of
      NIDDM patients while the presence of raised urinary AER was characterised by an
      increase in erythrocyte spermine (11 +/- 1.7 vs. 7.7 +/- 1.7 nmol/ml packed
      erythrocytes; P = 0.04) and spermidine (18.9 +/- 1.7 vs. 12.6 +/- 1.5 nmol/ml
      packed erythrocytes; P = 0.02), being both polyamines significantly related to
      AER and to metabolic control. Erythrocyte spermidine and spermine were moreover
      significantly higher in the group of patients with macroangiopathy (22.8 +/- 1.5
      vs. 12.3 +/- 1.5 nmol/ml; P = 0.0001 and 11.5 +/- 1.7 vs. 7.8 +/- 1.7 nmol/l
      packed erythrocytes; P = 0.04) and being, moreover, erythrocyte spermidine
      augmented in patients with retinopathy (24.2 +/- 1.5 vs. 12.2 +/- 1.5 nmol/ml
      packed erythrocytes; P = 0.009). In conclusion the levels of erythrocyte spermine
      and spermidine are both associated with the presence of albuminuria and
      macroangiopathy in NIDDM, while spermidine is on the average increased in the
      group of diabetic patients with retinopathy.

PMID- 9279474
TI  - Meformin, plasma glucose and free fatty acids in type II diabetic out-patients:
      results of a clinical study.
AB  - Abnormalities in free fatty acid (FFA) metabolism are an intrinsic feature of
      type II diabetes mellitus and may even play a role in the development of
      glycaemic imbalance. This study investigated whether the anti-diabetic drug
      metformin can reduce FFA levels in clinical practice and whether this correlates
      with its anti-diabetic effect. For 6 months metformin was added to sulfonylurea
      therapy in 68 type II diabetic outpatients with poor glycaemic control, being
      administered before meals and at bed-time. Basal and daily area-under-the-curve
      (AUC) glucose levels dropped (both P < 0.0005) like basal and daily AUC FFA
      levels (P < 0.004 and P < 0.001 respectively) reductions were all correlated (P <
      0.001 and P < 0.003 respectively). Reductions in fasting and daily AUC glucose
      correlated more closely with body fat distribution, expressed by waist-hip ratio
      (WHR) (P < 0.006 and P < 0.004 respectively), than with the body mass index (BMI)
      (P < 0.02 and P < 0.04 respectively). Similarly fasting and daily AUC FFA
      correlated with WHR (P < 0.007 and P < 0.01 respectively) but not with BMI (both
      P = ns). Subdividing male and female diabetic patients into groups with low and
      high WHRs, fasting and daily AUC glucose were reduced in men (P < 0.01 and P <
      0.02) and in women (P < 0.02 and P < 0.04 respectively) with low WHRs less than
      in men and in women with higher WHRs (for each gender P < 0.0001 and P < 0.0002,
      respectively). Decreases in fasting and daily AUC FFA, which did not reach
      significance in either men or women with low WHRs, were statistically significant
      in men (P < 0.03 and P < 0.01 respectively) and in women (P < 0.02 and P < 0.005
      respectively) with high WHRs. These findings suggest that an improvement in FFA
      plasma levels might contribute to metformin's anti-diabetic activity which
      appears to be more marked in patients with high WHRs. Moreover adding a bed-time
      dosage to the standard administration at meal times seems to be an effective
      therapeutical strategy.

PMID- 9279475
TI  - Detection and treatment of hypertension in patients with non-insulin-dependent
      diabetes mellitus: does the 'rule of halves' apply to a diabetic population?
AB  - The extent to which hypertension is detected and adequately treated in the
      general population is often described by the 'rule of halves', but corresponding
      figures for patients with non-insulin-dependent diabetes mellitus (NIDDM), based
      on current American Diabetes Association (ADA) criteria, have not been previously
      reported. This study looked at the detection and management of hypertension among
      2331 consecutive patients with NIDDM attending for annual complications
      assessment. Hypertension was defined according to ADA criteria, i.e. systolic
      blood pressure (sBP) > 140 mmHg and/or diastolic blood pressure (dBP) > 90 mmHg.
      A total of 69% of patients were hypertensive, with proportionately more women in
      the hypertensive group (48 versus 39%, P < 0.002). Among those with hypertension,
      59% were taking antihypertensive drugs but only 31% of treated hypertensives were
      adequately controlled. Thus, hypertension affects roughly two-thirds of patients
      with NIDDM and compared with treatment strategies reported in the literature for
      the non-diabetic population (summarised in the 'rule of halves'), proportionately
      more hypertensive patients with NIDDM are treated with BP-lowering drugs (59%)
      but proportionately less (31%) have adequate BP control.

PMID- 9279476
TI  - Mortality following lower extremity amputation in minorities with diabetes
      mellitus.
AB  - The aim of this study was to identify the age adjusted and level specific
      mortality rate in African-Americans, Hispanics and non-Hispanic whites (NHW)
      during the perioperative period following a lower extremity amputation. We
      identified amputation data obtained from the Office of Statewide Planning and
      Development in California for 1991 from ICD-9-CM codes 84.11-84.18 and diabetes
      mellitus from any 250 related code. Amputations were categorized as foot (84.11
      84.12), leg (84.13-84.16) or thigh (84.17-84.18). Death was coded under discharge
      status. Age adjusted and level specific mortality rates per 1000 amputees were
      calculated for each race/ethnic group. The age adjusted mortality was highest for
      African-Americans (41.39) compared to Hispanics (19.69) and NHW's (34.98).
      Mortality was consistently more frequent for proximal amputations. We conclude
      that mortality rates for persons with diabetes hospitalized for an amputation
      varied by race, gender and level of amputation. Higher prevalence or severity of
      risk factors may explain the excess mortality observed in African-Americans.

PMID- 9279477
TI  - Acute effects of phorbol ester and insulin on insulin-induced glucose uptake and
      protein kinase C activation in rat adipocytes.
AB  - We examined the acute effect of pretreatment with phorbol ester and insulin on
      insulin-induced glucose uptake and protein kinase C (PKC) translocation from
      cytosol to the membrane in rat adipocytes. Adipocytes were preincubated with 1
      microM tetradecanoylphorbol 13-acetate (TPA) and 10 nM insulin for 60 min and
      then stimulated with 10 nM insulin for 10 and 30 min to measure PKC activity in
      cytosol and membrane fractions using a Mono Q column connected onto an HPLC
      system and [3H]2-deoxyglucose (DOG) uptake, respectively. Pretreatment with 1
      microM TPA and 10 nM insulin for 60 min resulted in the marked decreases of
      insulin-induced [3H]2-DOG uptake. Translocation of Mono Q column-purified
      cytosolic PKC enzyme activity and PKC beta immunoreactivity from cytosol to the
      membrane was suppressed by pretreatment with TPA and insulin for 60 min. These
      results indicate that acute treatment with TPA and insulin which are PKC
      activators suppress translocation/activation of PKC, and accordingly inhibit
      insulin-induced glucose uptake. We suggest that a decrease of cytosolic PKC
      activity may mainly-contribute to the impaired responsiveness of the glucose
      transport system after acute TPA and insulin treatment.

PMID- 9279478
TI  - Insulin degradation by Madin-Darby canine kidney cells expressing the insulin
      receptor.
AB  - Prior studies have shown that Madin-Darby canine kidney cells (MDCK)
      overexpressing the human insulin receptor bind and respond normally to insulin
      (T.C. Yeh, R.A. Roth, Diabetes 43 (1994) 1297-1303). Moreover, the insulin
      receptor preferentially localizes to the basolateral membrane of these cells. In
      the present studies, insulin was added to either the apical or the basolateral
      side of these cells and the extent of degradation of the insulin was assessed.
      Radioactive insulin added to either side was bound to its receptor and the
      radioactivity which reached the other side of the cell was to a large extent
      degraded fragments. Insulin added to the apical side was degraded to a larger
      extent (83%) than when added to the basolateral side (49%) although the
      basolateral side has much more insulin receptors than the apical side. This
      degradation process was not inhibitors of either lysosomal enzymes, the
      proteasome complex or cathepsins. The degradation process could however, be
      potently inhibited by the sulfhydryl alkylating agent N-ethylmaleimide. Further,
      cell surface biotinylation study showed that the insulin degrading enzyme was
      preferentially localized on the apical membranes. These results suggest that
      insulin added on the apical side of MDCK cells are more closely linked to the
      degradation process than that added on the basolateral side.

PMID- 9279479
TI  - Effect of an alpha-glucosidase inhibitor on glomerular basement membrane anionic
      sites in streptozotocin induced mildly diabetic rats.
AB  - The present study was conducted in order to examine the effect of acarbose, a
      potent alpha-glucosidase inhibitor, on renal function in rats with mild
      streptozotocin-diabetes. Male Wistar rats were made mildly diabetic by
      intravenous injection of streptozotocin (40 mg/kg) and were supplied a standard
      solid chow containing 0.1% acarbose for 8 weeks. Diabetic rats showed mild
      hyperglycemia under non-fasting condition and their urine albumin excretion (UAE)
      rate was markedly increased compared to non-diabetic control rats, while acarbose
      treatment resulted in a significant suppression of blood glucose level and UAE in
      diabetic rats. Examination by electron microscope revealed that the number of
      anionic sites in the lamina rara externa per 1000 nm of glomerular basement
      membrane (GBM) was significantly decreased in diabetic rats compared to control
      value (15.7 +/- 0.9 vs. 20.9 +/- 0.3 P < 0.001), whereas, significant recovery
      (19.6 +/- 0.6 P < 0.01) was observed after 8 weeks of acarbose treatment. In
      conclusion, acarbose treatment suppressed blood glucose level of mildly-insulin
      deficient animal model without insulin treatment and prevented from a reduction
      in the number of anionic sites in GBM which might ameliorate an increased
      permeability of GBM leading to albuminuria.

PMID- 9279480
TI  - High glucose inhibits effect of ascorbic acid on [35S] sulphate incorporation in
      mesangial cell and matrix proteoglycan.
AB  - Expansion of the glomerular mesangium is a consistent finding of diabetic
      nephropathy. Negatively charged proteoglycans are an integral part of the
      mesangium and their synthesis and degradation is disturbed in many forms of
      glomerulosclerosis. The metabolism of ascorbic acid (AA), which plays an
      important role in extracellular matrix regulation, is known to be abnormal in
      diabetes. The action of AA has also been shown to be inhibited by high glucose
      (HG) concentration. In this study we investigated the effect of AA and HG on
      proteoglycan (PG) synthesis by examining the incorporation of [35S] sulphate into
      PG in the cellular, matrix and media components of rat mesangial cell (MC)
      cultures. MC were grown in 9 or 25 mM glucose for 8 days, with and without the
      addition of AA. Sulphation of PG was measured by adding 50 microCi of [35S]
      sulphuric acid to the culture medium and precipitating 35S-labelled PG with
      cetylpyridinium chloride. In this study AA was shown to have a stimulatory effect
      on the overall incorporation of [35S] sulphate into cell and matrix PG and this
      was inhibited by 25 mM glucose. Correcting for protein synthesis and specific
      activity of [35S] sulphate showed that HG inhibits AA stimulation by decreasing
      sulphation of the individual PG molecules. These findings may be of particular
      importance in the pathophysiology of nephropathy in diabetes, a condition where
      AA concentration is already compromised.

PMID- 9279481
TI  - Endothelin-1 and endothelin-3-like immunoreactivity in the eyes of diabetic and
      non-diabetic BB/W rats.
AB  - Endothelins (ETs) are a family of vasoactive peptides implicated in several
      disorders of the microvasculature. In the present study, the distribution of
      immunoreactive ET-1 and ET-3 was investigated in eyes from 8 month spontaneously
      diabetic BB/W rats and in age matched control animals. Both peptides showed
      similar immunoreactivity. In non-diabetic animals, corneal epithelium and
      endothelium, ciliary epithelium, lens epithelium, iris and the microvasculature
      of the sclera and choroid showed positive immunoreactivity. In the retina,
      photoreceptor inner segments showed positivity. In the inner nuclear layer, cells
      of both neuronal and glial origins showed positive immunoreactivity. Both the
      nuclei and the cytoplasm of the ganglion cells were positively stained. Retinal
      pigment epithelium showed patchy but consistent immunoreactivity. Capillary
      endothelial cells showed inconsistent positive staining. The pericytes were
      uniformly negative. In diabetic animals although overall intensity was increased,
      retinal pigment epithelium and ciliary epithelium showed no immunoreactivity. The
      corneal epithelium showed increased but patchy immunoreactivity. The altered
      intensity and distribution of ETs in diabetes suggest that ETs may be of
      importance in the pathogenesis of chronic occular complications in the diabetic
      BB/W rat.

PMID- 9279482
TI  - Will older sedentary people with non-insulin-dependent diabetes mellitus start
      exercising? A health promotion model.
AB  - Exercise and diet are the cornerstones of management of non-insulin-dependent
      diabetes mellitus (NIDDM). Many older people have difficulty in exercising,
      missing benefits on glycaemic control, weight, cardiac disease and mood. We
      report the outcomes of a 6 month structured exercise and support programme based
      on a health promotion model, on physical activity, glycaemic control and
      parameters of cardiovascular risk in non-exercisers, compared with standard
      outpatient clinic education. A total of 26 non-exercising patients were
      randomised to an intervention or control group (ten men, 16 women; mean age (+/-
      S.D.) 60 +/- 8 years). Programme participation was not associated with any
      significant increase in activity. Glycated hemoglobin (HbAtc) levels tended to
      stabilise in the intervention group during the 6 month programme and to
      deteriorate in the control group (P = 0.03); by 12 months HbA1C levels
      deteriorated to a similar level in both. Programme participation did not cause
      significant change in anthropometric or metabolic parameters. Examining the
      cohort as a whole, increased activity over 6 months was associated with
      improvements in weight, body mass index (BMI), body fat and fasting insulin.
      Activity increases over 12 months were associated with improvements in weight and
      BMI. These changes could not be attributed to changes in energy intake or dietary
      composition. We conclude that while exercise can benefit older people with NIDDM,
      a programme based on a model of health promotion was not effective in increasing
      physical activity.

PMID- 9279483
TI  - Effect of acarbose on glucose intolerance in patients with non-insulin-dependent
      diabetes mellitus.
AB  - We evaluated the effect of acarbose, an alpha-glucosidase inhibitor, on glucose
      intolerance in patients with non-insulin-dependent diabetes mellitus (NIDDM).
      Acarbose was given orally (300 mg/day) for 24 weeks to 20 NIDDM patients. Data in
      an oral glucose tolerance test (OGTT) were evaluated before and after 24 weeks of
      treatment using principal component analysis. Acarbose administration
      significantly reduced the postprandial plasma glucose level over 24 weeks of
      treatment. Principal component analysis suggested that the patients were
      separated into responders and non-responders. There was a significant improvement
      of fasting and postprandial glucose levels after 12 and 24 weeks in the
      responders, but not in the non-responders. Plasma glucose level following the
      OGTT improved significantly after 24 weeks of treatment in the responders
      (Hotelling T2 value = 47.098, P = 0.022500), but not in the non-responders. The
      immunoreactive insulin level did not change in either group. Results thus suggest
      that acarbose improved insulin resistance in some patients with NIDDM (responders
      as classified by principal component analysis).

PMID- 9279484
TI  - Limited joint mobility of the ankle in diabetic patients with cutaneous sensory
      deficit.
AB  - Limited joint mobility (LJM) of the ankle joint was measured in 48 diabetic
      patients classified into three groups: Insulin-dependent diabetes mellitus (IDDM
      = 15), non-insulin diabetes mellitus (NIDDM = 12) and patients with cutaneous
      sensory deficit in the foot (CD = 21). Specifically, plantar flexion,
      dorsiflexion and total range of motion was measured on both feet using
      goniometric techniques during active and passive movement conditions. No
      significant bilateral differences were established, therefore values for the
      right foot were used for statistical analyses. Diabetic patients were matched to
      48 non-diabetic controls for age, weight and gender factors. A Semmes-Weinstein
      monofilament test was used on both feet to assess the integrity of cutaneous
      sensitivity in all patient and control subjects. Cutaneous sensory deficit
      patients (CD) had monofilament values greater than two standard deviations below
      control group mean values. There were no significant differences between the
      monofilament test values for the IDDM and NIDDM patients and control group data.
      LJM results indicated both plantar flexion and range of motion in CD patients
      under active and passive movement conditions were significantly reduced compared
      to control group data. No differences were observed for any pairwise comparisons
      between the IDDM and NIDDM groups compared to controls. The data is discussed in
      terms of the interaction between LJM in the foot and type of diabetic
      classification.

PMID- 9279485
TI  - High proinsulin levels in late PRE-IDDM stage.
AB  - AIM: To analyse the fasting proinsulin levels in first degree relatives of
      patients with insulin-dependent diabetes mellitus (IDDM) with different risk for
      developing the disease. PATIENTS AND METHODS: Non siblings first degree
      relatives, 33, of IDDM patients were separated into three groups with different
      risk for developing IDDM: Group 1, 14 first degree relatives (eight male/six
      female), aged from 18 to 57 years, normal first phase insulin release (FPIR) in
      the intravenous glucose tolerance test, negative ICA; Group 2, 11 first degree
      relatives (six male/five female), aged from 16 to 62 years, normal FPIR and ICA <
      20 JDF U; Group 3, eight first degree (six male/two female), from 16 to 52 years,
      FPIR diminished and ICA > 20 JDF U. All patients had normal oral glucose
      tolerance test at the initiation of the study. We tested fasting proinsulin (PRO)
      and insulin (IRI) levels by radioimmunoassay (RIA) and the PRO/IRI ratio.
      RESULTS: Four first degree from the group 3 developed IDDM after 2-32 months. No
      differences were observed in-fasting PRO levels and PRO/IRI ratio between the
      groups. However, the PRO (21.7 +/- 5.8 pmol/l) and PRO/IRI ratio (0.29 +/- 0.10)
      levels of the subjects who developed IDDM were significantly higher (P < 0.05)
      than those values obtained in subjects who did not developed the disease.
      CONCLUSION: these data indicate that fasting PRO levels and the PRO/IRI ratio may
      be an additional marker in post-puberty first-degree relatives of IDDM patients
      with immunological and metabolic evidence of high risk for developing the
      disease.

PMID- 9279486
TI  - Prevalence of low back pain among physical therapists in Edmonton, Canada.
AB  - Questionnaires were sent to 462 physical therapists in Edmonton, Canada, to
      determine the prevalence of work-related low back pain (LBP) and to characterize
      those who reported pain. Of the 311 (67.3%) valid questionnaires returned. 49.2%
      reported back pain due to work. The occurrence rates of work-related LBP among
      physical therapists in Edmonton was higher than that of the general population
      reported in Canada (27%), Great Britain (27%), and the United States (26-29%).
      There was no significant difference (p < or = 0.05) between those with and
      without work-related LBP. The initial onset of work-related LBP frequently
      occurred within the first 5 years of practice as a physical therapist, and before
      the age of 30. Hospitals and private practices were the most prevalent work
      settings in which injury occurred. Patient handling, bending, stooping, lifting,
      carrying, pushing, and pulling were the commonly described activities causing
      precipitation of injury. The severity of back discomfort had been sufficient to
      require 13.7% of therapists to stop their work. Despite LBP, 35.3% of the pain
      sufferers continued to work. Over half (55.4%) of the respondents with current
      work-related LBP demonstrated little or no disability.

PMID- 9279487
TI  - Prescription pattern for orthoses in The Netherlands: use and experience in the
      ambulatory phase of Duchenne muscular dystrophy.
AB  - In the Netherlands ankle-foot orthoses (AFO), standing frames (SF), knee-ankle
      foot orthoses (KAFO) and orthopaedic footwear are frequently prescribed for
      patients with Duchenne muscular dystrophy. Little is known, however, about the
      prescription pattern and the experience of patients. A questionnaire was sent to
      25 rehabilitation physicians treating 53 patients with Duchenne muscular
      dystrophy. The use of orthoses and the patients' experience was measured during 1
      year of follow-up. Our results show prescription of AFO 91%, of SF 61% and of
      KAFO 22%. Indications were limited passive dorsiflexion and Vignos classification
      6. Patient-related factors were reasons to discontinue or to refrain from using
      orthoses. The prescribed duration for KAFO varied greatly. Patients' experience
      scores for SF and KAFO were high. The time that the orthoses were worn differed
      greatly from the recommended time. Ready-made shoes were prescribed for
      equinovarus during ambulation. Similarly, ready-made shoes or custom-made shoes
      were advised for wheelchair-dependent patients. This study shows no uniform
      prescription pattern for AFO, SF. KAFO and orthopaedic footwear. The prescription
      pattern was influenced by patient-related factors and actual use greatly differed
      from the recommended time.

PMID- 9279489
TI  - Relationship between use of technology and employment rates for people with
      physical disabilities in Australia: implications for education and training
      programmes.
AB  - This study examined the impact of computer and assistive device use on the
      employment status and vocational modes of people with physical disabilities in
      Australia. A survey was distributed to people over 15 years in age with physical
      disabilities living in the Brisbane area. Responses were received from 82 people,
      including those with spinal cord injuries, cerebral palsy and muscular dystrophy.
      Of respondents 46 were employed, 22 were unemployed, and 12 were either students
      or undertaking voluntary work. Three-quarters of respondents used a computer in
      their occupations, while 15 used assistive devices. Using logistic regression
      analysis it was found that gender, education, level of computer skill and
      computer training were significant predictors of employment outcomes. Neither the
      age of respondent nor use of assistive software were significant predictors. From
      information obtained in this study guidelines for a training programme designed
      to maximize the employability of people with physical disabilities were
      developed.

PMID- 9279488
TI  - Effect of manual therapy techniques on the stretch reflex in normal human
      quadriceps.
AB  - The effect of four manual therapy techniques on the quadriceps stretch reflex
      amplitude (elicited by mechanical vibration) was studied in a randomized,
      controlled trial in 120 (20 in each of six groups) healthy human subjects aged 18
      64 years. Passive and active techniques were studied; each under static and
      dynamic conditions. The passive procedures were massage (static) and knee
      oscillation (dynamic) for 5 min. Active techniques involved eight repetitions of
      isometric quadriceps contractions (static) and leg extension (dynamic). The two
      static techniques had no effect on the stretch reflex amplitude. Both dynamic
      techniques caused a reduction (active by 25%, p < 0.00001 and passive 12%, p <
      0.05). Only the active, dynamic technique caused a greater change than in the
      control group (p < 0.005). The effect lasted for less than 1 min. These data
      question the ability of such techniques to make clinically valid changes in
      motoneuron excitability. Further studies are required on those with neuromuscular
      pathology, who may respond differently to normal subjects.

PMID- 9279491
TI  - An estimation of the functional disability burden in elderly Chinese age 70 years
      and over.

PMID- 9279490
TI  - 'Oh, don't you envy us our privileged lives?' A review of the disability culture
      movement.

PMID- 9279492
TI  - Dissociation between subjective and behavioral responses after cocaine stimuli
      presentations.
AB  - This study was designed to explore the relationship between craving and cocaine
      seeking behavior with the use of both subjective and behavioral measures. Five
      males and five females who have used crack at least two times a week for 6
      months, and who reported using 0.5 g of crack within 24 h on at least one
      occasion, participated in an inpatient study. Subjects underwent a total of four
      experimental sessions, during which they were exposed to either neutral (Neutral
      Stimuli Condition) or cocaine-related (Cocaine Stimuli Condition) external and
      internal stimuli. Subjects were exposed to each stimuli condition twice, on
      separate days, in randomized order. External stimuli comprised neutral or cocaine
      related videotapes and paraphernalia, and the internal stimulus was either a 5-mg
      ('placebo') or 0.4 mg/kg delivery of cocaine. At baseline and after each stimulus
      exposure, subjects completed a composite cocaine craving questionnaire. Subjects
      next worked on concurrently-available fixed-ratio tasks either for tokens that
      could be exchanged for money ($2) or for tokens that were exchangeable for
      deliveries of cocaine (0.4 mg/kg). The results show that subjects reported
      significantly greater cocaine craving after exposure to cocaine-related vs.
      neutral stimuli, indicating that craving for cocaine can be successfully modeled
      in a laboratory setting. However, this change in subjective response did not
      predict drug-seeking behavior. The number of cocaine tokens earned following
      exposure to the cocaine-related vs neutral stimuli was similar. These results
      suggest that in a laboratory setting, craving may be unrelated to cocaine-seeking
      behavior in non-treatment-seeking cocaine users.

PMID- 9279494
TI  - Prevalence of youth substance use: the impact of methodological differences
      between two national surveys.
AB  - This study compared two major Federally sponsored surveys of adolescent substance
      use and assessed the impact that methodological differences have on the
      prevalence estimates they generate. The Monitoring the Future Survey, a school
      based survey, was compared to the National Household Survey on Drug Abuse, a
      household survey of the population aged 12 years and older. Response rates were
      higher in the household survey due to high rates of refusal in the school based
      survey. The school survey has a larger overall sample size, but sampling errors
      more similar than one might expect, because of the larger design effects in the
      school survey. Rates of drug use obtained were larger in the school survey than
      in the household survey, possibly because of greater under-reporting in the
      household setting than in the classroom and the different questionnaires used in
      the two surveys.

PMID- 9279493
TI  - Maintenance of HIV risk reduction among injection opioid users: a 12 month
      posttreatment follow-up.
AB  - Study objectives were to examine HIV risk behaviors 12 months following methadone
      maintenance (MM) treatment termination, and to assess the effects of treatment
      tenure, cocaine use, and gender on posttreatment HIV risk. Injection and sex risk
      behaviors were measured at treatment entry and 12 months after leaving treatment
      among 435 injection opioid users. Multi-way contingency tables for treatment
      tenure and HIV risk at treatment intake and at 12 month follow-up were analyzed
      using the GSK weighted least-squares estimation procedure. The effects of
      treatment tenure, gender, and cocaine use on risk behavior at follow-up, while
      controlling for intake risk and background variables were tested using a series
      of multiple logistic regression analyses. Results showed that injection and sex
      risk behaviors were significantly lower at 12 month follow-up than at treatment
      entry. Additionally, increased tenure was related to risk reductions, while
      cocaine use was related to increased risk-taking. Gender was generally unrelated
      to risk changes. These findings support broader use of MM in helping reduce HIV
      risks among injection drug users and highlight the need to explore ways to
      encourage treatment compliance in order to reduce risky practices.

PMID- 9279495
TI  - Processes of change assessment in heroin addicts following the Prochaska and
      DiClemente transtheoretical model.
AB  - The processes of change dimension of Prochaska and DiClemente's transtheoretical
      model of change is tested in a sample of opiate addicts for the first time. A
      self-report (The Processes of Change Inventory for Opiate Addicts, PCI-OA)
      designed to assess the frequency of processes of change was administered in a
      sample of 178 heroin addicts in order to study its reliability, validity and
      discriminative efficiency. An alpha-reliability coefficient of 0.87 was obtained.
      A principal component analysis of the measure revealed a three-component solution
      which accounted for 34% of the variance: 'contemplation and preparation
      processes', 'processes of action', and 'processes of the final part of the action
      phase and maintenance'. Comparisons between abstinent and non-abstinent subjects
      revealed significant differences (P < 0.0001) in two of the ten processes
      considered: counterconditioning and stimulus control. A stepwise discriminant
      analysis yielded a linear combination of eight processes that correctly
      identified 78% of the total sample. Theoretical and clinical implications of the
      results are discussed, suggesting that the PCI-OA can be considered as a useful
      self-report instrument for identifying which processes of change are being used
      by a specific opiate-dependent patient.

PMID- 9279496
TI  - Psychoactive substance abuse among inmates of a Nigerian prison population.
AB  - The objectives of the study were: (1) to assess the prevalence rate of
      psychoactive substance use and dependence among inmates of a Nigerian prison
      population within the past month; (2) to highlight how aware these prisoners
      were, of the various drugs of abuse; (3) to compare the findings with those of
      reports from abroad, and general Nigerian population samples. In mid-1995, 395
      subjects (97.5% males, mean age 30.5 years) were interviewed, with a
      questionnaire that contained DSM-III-R criteria for dependence. About two-thirds
      were those on remand or awaiting trial, and the majority (70%) were accused of
      theft and armed robbery. Compared with Nigerian general population samples, the
      cohort had much higher prevalence rates of awareness and life-time use of
      psychoactive substances. Cannabis was the only drug regularly abused in the past
      month, by 26 (6.6%) subjects (all males); out of whom 11 (42.3%) satisfied DSM
      III-R criteria for dependence. Use of intravenous drugs was not evident. This
      pattern differed markedly from the situation in industrialised countries.
      Cannabis abuse was significantly associated with those in prison for less than
      six months and on a charge of theft/armed robbery.

PMID- 9279497
TI  - A comparison of blood toxicology of heroin-related deaths and current heroin
      users in Sydney, Australia.
AB  - Blood toxicology results for deaths attributed to heroin overdose during 1995 in
      the South Western Sydney (SWS) region (n = 39) were compared with those of a
      sample of 100 current SWS heroin users who had injected within the preceding 24
      h. Heroin-related deaths had a higher median concentration of morphine than
      current heroin users (0.35 versus 0.09 mg/l). However, there was substantial
      overlap between the blood morphine concentrations of the two groups, ranging from
      0.08-1.45 mg/l. This range incorporated 90% of heroin-related deaths. A third of
      current users had morphine concentrations over twice the toxic blood morphine
      concentration employed by the analytical laboratories, and 7% had morphine levels
      higher than the median recorded for fatal cases. Alcohol was detected in 51% of
      fatal cases (median = 0.10 g/100 ml) compared with 1% of current heroin user.
      There was a significant negative correlation among fatal cases between blood
      morphine and blood alcohol concentrations (r2 = -0.41). There was no significant
      difference between groups in the proportions of subjects positive for blood
      benzodiazepines. The results raise questions about the mechanisms of death in
      what are termed overdoses, and about the role of alcohol in these fatalities.

PMID- 9279498
TI  - Treatment outcome of cocaine-alcohol dependent patients.
AB  - Cocaine dependent patients (n = 27) with and without concurrent alcohol
      dependence disorder were compared on measures of substance use, addiction
      severity (ASI), coping, and psychopathology taken before, during, and after
      outpatient relapse prevention treatment for cocaine dependence. At pre-treatment,
      the cocaine-alcohol (CA) group reported more frequent alcohol use, and more
      severe alcohol and family/social problems compared to the cocaine-only (CO)
      group. By the end of treatment, both groups reported significantly fewer days of
      alcohol and cocaine use, with sustained reductions observed at 24 weeks following
      treatment. On most of the addiction severity and psychiatric symptomatology
      scales, results indicated overall improvement as a function of time, however
      scores remained relatively 'worse' in the CA group. Implication of these findings
      and the need for specific programming in the treatment of dual drug use are
      explored.

PMID- 9279499
TI  - Statement on national drug policy. College on problems of drug dependence.

PMID- 9279500
TI  - Drug treatment of non-insulin-dependent diabetes mellitus in the 1990s.
      Achievements and future developments.
AB  - Non-insulin-dependent diabetes mellitus (NIDDM, type 2 diabetes) is a
      heterogeneous disease resulting from a dynamic interaction between defects in
      insulin secretion and insulin action. There are various pharmacological
      approaches to improving glucose homeostasis, but those currently used in clinical
      practice either do not succeed in restoring normoglycaemia in most patients or
      fail after a variable period of time. For glycaemic regulation, 4 classes of
      drugs are currently available: sulphonylureas, biguanides (metformin), alpha
      glucosidase inhibitors (acarbose) and insulin, each of which has a different mode
      and site of action. These standard pharmacological treatments may be used
      individually for certain types of patients, or may be combined in a stepwise
      fashion to provide more ideal glycaemic control for most patients. Adjunct
      treatments comprise a few pharmacological approaches which may help to improve
      glycaemic control by correcting some abnormalities frequently associated with
      NIDDM, such as obesity (serotoninergic anorectic agents) and hyperlipidaemia
      (benfluorex). There is intensive pharmaceutical research to find new drugs able
      to stimulate insulin secretion (new sulphonylurea or nonsulphonylurea
      derivatives, glucagon-like peptide-1), improve insulin action
      (thiazolidinediones, lipid interfering agents, glucagon antagonists, vanadium
      compounds) or reduce carbohydrate absorption (miglitol, amylin analogues,
      glucagon-like peptide-1). Further studies should demonstrate the superiority of
      these new compounds over the standard antidiabetic agents as well as their
      optimal mode of administration, alone or in combination with currently available
      drugs.

PMID- 9279503
TI  - Peripheral diabetic neuropathy. Current recommendations and future prospects for
      its prevention and management.
AB  - One-third of diabetic patients are affected by peripheral neuropathy (PDN) in
      which the main aetiopathogenetic mechanism seems to be the high blood and nerve
      glucose content. The results of some long term trials, such as the Diabetes
      Control and Complications Trial (DCCT) and Stockholm studies, showed clearly that
      the maintenance of near-normal blood glucose levels and haemoglobin (Hb)A1c below
      7.5% with intensive insulin treatment represents the best approach to primary and
      secondary prevention of the late diabetic complications, including PDN. After 5
      years of such treatment DCCT reported that the development of clinical PDN was
      reduced by 64%. On the other hand, various and important problems still exist in
      identifying an efficacious aetiological therapy for PDN. In fact, while on the
      basis of current knowledge we have 2 possibilities for treatment of the pain,
      optimisation of glycaemic and HbA1c values and correct use of tricyclic
      antidepressants, none of the various substances tested has proven to be
      efficacious for PDN. Gangliosides, aldose-reductase inhibitors, including
      tolrestat, gamma-linolenic acid, levacecarnine (acetyl-L-carnitine) and
      antioxidants, were all shown to be of poor efficacy and often with significant
      adverse effects. The maintenance of near-normal glycaemic equilibrium seems
      currently to be the best way not only to prevent PDN but also to treat it. In the
      near future more long term trials, with very clear inclusion and exclusion
      criteria for recruitment, are needed to assist in identifying an efficacious
      treatment for PDN.

PMID- 9279501
TI  - Leukotriene activity modulation in asthma.
AB  - Leukotrienes constitute a class of inflammatory mediators synthesised from
      arachidonic acid, a product of cell membrane metabolism. Synthesis occurs in the
      5-lipoxygenase enzyme pathway, which produces several species of leukotrienes,
      each with characteristic biological activities. With regard to asthma, the
      leukotrienes are particularly important because of their ability to directly and
      potently mediate bronchoconstriction; in addition, they specifically stimulate
      the secretion of mucus into the airways and the extravasation of fluids and
      proteins into the airway tissues, both of which contribute to airway obstruction.
      A number of antileukotriene agents have been developed with the goal of
      modulating the inflammatory process in various disease states. These agents fall
      into 2 general classes: leukotriene receptor antagonists and leukotriene
      synthesis inhibitors. Results of antileukotriene agents in preclinical and
      clinical trials indicate that antileukotriene agents attenuate the response to
      challenges with inhaled leukotrienes, cold air, exercise, aspirin and allergen;
      in addition, they have shown efficacy in clinical asthma and have not been
      associated with serious adverse effects. Although results to date indicate that
      these medications are well tolerated and effective in the treatment of asthma,
      the recent approval by the FDA of 2 antileukotriene agents will give physicians
      further insight into how patients with asthma respond to them.

PMID- 9279505
TI  - Trovafloxacin.
AB  - Trovafloxacin is a fluoroquinolone antibacterial agent with a broad spectrum of
      activity. Trovafloxacin has similar or 2-fold lower activity than ciprofloxacin
      against Enterobacteriaceae and Pseudomonas aeruginosa. Against Haemophilus
      influenzae and Moraxella catarrhalis, trovafloxacin has similar activity to
      ciprofloxacin. Other susceptible Gram-negative pathogens include Neisseria
      gonorrhoeae, Chlamydia trachomatis and mycoplasmas. The drug is active against
      Gram-positive bacteria and consistently displayed greater activity (2- to 8-fold)
      than ciprofloxacin against all staphylococci and streptococci tested; activity
      included methicillin-resistant staphylococci and penicillin-resistant
      Streptococcus pneumoniae. Trovafloxacin has some activity against vancomycin
      resistant enterococci. Anaerobes such as Bacteroides and Clostridium spp. are
      also susceptible to trovafloxacin. Preliminary clinical data suggest that
      trovafloxacin is effective in the treatment of patients with upper and lower
      respiratory tract and uncomplicated urinary tract infections and infections
      caused by C. trachomatis or N. gonorrhoeae. The most frequently noted adverse
      event with trovafloxacin is dizziness which is reported in 11% of patients versus
      3% of those receiving comparator agents. Other commonly reported events (> 1% of
      patients) are nausea, headache, vomiting, vaginitis and diarrhoea.

PMID- 9279504
TI  - Recognition and management of systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an inflammatory systemic disease that
      causes organ damage by the deposition of autoantibodies and complement activating
      immune complexes or by vascular occlusion due to procoagulant states associated
      with antiphospholipid antibodies. The vast majority of cases occur in women of
      childbearing age. SLE is diagnosed on the basis of its clinical manifestations
      and the demonstration of characteristic immunological phenomena, especially anti
      nuclear antibodies. The prognosis in SLE has shown a distinct improvement over
      recent decades, the 5-year survival rate now approaching or exceeding 90%. The 15
      year survival rate of 63 to 79%, on the other hand, underscores the need for
      further advances in diagnosis and treatment of the disease. Management of the
      disease includes regular monitoring of disease activity, avoidance of
      predisposing factors and close supervision of therapy. Drug therapy is guided by
      the activity and severity of the leading organ manifestations and ranges from
      nonsteroidal antirheumatic drugs to intensive treatment with cytotoxic agents.
      Corticosteroids remain irreplaceable for the control of acute flares.
      Antimalarials and azathioprine are important long term drugs for treating mild or
      moderate disease activity. Intravenous pulse cyclophosphamide is safer than other
      regimens and at least as effective as oral cyclophosphamide for severe lupus
      nephritis. It is also effective in the treatment of central nervous disease and
      of other organ-threatening manifestations. Recently, an intensified protocol
      which included cyclophosphamide induced long term treatment-free remission in 60%
      of patients. The toxicity of cyclophosphamide is considerable, but can be
      ameliorated by various measures. The value of several new immunosuppressants and
      other compounds remains to be determined.

PMID- 9279502
TI  - Breast cancer therapies in development. A review of their pharmacology and
      clinical potential.
AB  - Although the management of breast cancer has improved over the past few decades,
      it remains an important challenge for the clinician. Cytotoxic chemotherapy and
      hormonotherapy, when given in the adjuvant setting, have a definitive though
      modest impact on the outcome of early-stage breast cancer. In metastatic disease,
      these therapies help to provide substantial palliation of symptoms but have a
      limited impact on survival. The discovery of vinorelbine and the taxanes,
      paclitaxel and docetaxel, certainly represented the most encouraging clinical
      development of the 1980s in breast cancer therapy. Several other new cytotoxic
      agents have been recognised for their potential in the treatment of this
      disorder. Many of them are only in a very early phase of their clinical
      development and it remains to be proven that they will have a major role in daily
      practice in the near future.

PMID- 9279508
TI  - Changes in ovarian expression of tissue-type plasminogen activator and
      plasminogen activator inhibitor type-1 messenger ribonucleic acids during
      ovulation in rat.
AB  - We investigated the time course and localization of ovarian tissue-type
      plasminogen activator (tPA) and plasminogen activator inhibitor type-1 (PAI-1)
      expression during the ovulatory period in rat by RNase protection assay and in
      situ hybridization. Immature female Wistar rats were injected with 25 IU pregnant
      mare serum gonadotropin (PMSG), followed 50 h later by 25 IU human chorionic
      gonadotropin (hCG). Levels of tPA mRNA were low before hormone treatment and
      after PMSG treatment. After hCG treatment, tPA mRNA levels increased rapidly, the
      first peak at 4 h after hCG treatment and reached a maximum just prior to
      ovulation, 12 h later, before declining again. PAI-1 mRNA was barely detectable
      before hormone treatment but was transiently induced by hCG treatment, reaching
      peak levels after 4 h. Subsequently, PAI-1 mRNA levels decreased until early
      luteinization. The expression of tPA mRNA 4 h after hCG treatment occurred mainly
      in the follicular thecal-interstitial cells, but was barely detectable in the
      granulosa cells, whereas 12 h after hCG treatment it was maximal in the granulosa
      cells of the large follicles destined to ovulate. PAI-1 mRNA was expressed mainly
      in ovarian stromal tissue and in the thecal external interstitial cells
      encapsulating the follicles at 4 h after hCG treatment. These results suggest
      that the temporal regulation of tPA biosynthesis after hCG induction depends on
      the cell types and size classes in the various ovarian compartments. PAI-1 may be
      produced by the stormal tissue and the thecal external interstitial cells and is
      perhaps implicated in structural changes during follicular growth, ovulation and
      luteinization.

PMID- 9279506
TI  - Gemcitabine. A review of its pharmacology and clinical potential in non-small
      cell lung cancer and pancreatic cancer.
AB  - Gemcitabine [2'-deoxy-2',2'-difluorocytidine monohydrochloride (beta isomer);
      dFdC] is a novel deoxycytidine analogue which was originally investigated for its
      antiviral effects but has since been developed as an anticancer therapy.
      Gemcitabine monotherapy produced an objective tumour response in 18 to 26% of
      patients with advanced non-small cell lung cancer (NSCLC) and appears to have
      similar efficacy to cisplatin plus etoposide. Objective response rates ranging
      from 26 to 54% were recorded when gemcitabine was combined with cisplatin, and 1
      year survival duration after such treatment ranged from 35 to 61%. Improvements
      in a range of NSCLC disease symptoms and/or in general performance status
      occurred in many patients who received gemcitabine, with or without cisplatin, in
      3 clinical trials. Gemcitabine appears to be cost effective compared with best
      supportive care for NSCLC. In addition, direct costs associated with
      administration of gemcitabine monotherapy may be lower than those for some other
      NSCLC chemotherapy options, according to retrospective cost-minimisation
      analyses. The combination of gemcitabine plus cisplatin was associated with a
      lower cost per tumour response than cisplatin plus etoposide or cisplatin plus
      vinorelbine, according to a retrospective cost-effectiveness analysis. In a
      single comparative study in patients with advanced pancreatic cancer, gemcitabine
      was more effective than fluorouracil with respect to survival duration and
      general clinical status. It also showed modest antitumour and palliative efficacy
      in patients refractory to fluorouracil. Gemcitabine appears to be well tolerated,
      although further comparisons with other chemotherapy regimens are required. The
      available data indicate that gemcitabine monotherapy is better tolerated than
      cisplatin plus etoposide in patients with NSCLC. Data from noncomparative studies
      suggest that the combination of gemcitabine and cisplatin has an acceptable
      tolerabilty profile. In a single trial in patients with pancreatic cancer,
      fluorouracil was better tolerated than gemcitabine; however, gemcitabine was
      generally well tolerated overall in this study. Thus, gemcitabine (with or
      without cisplatin) may prove attractive to patients with advanced NSCLC, given
      their limited life expectancy and the toxicity associated with many other
      chemotherapy regimens. More detailed characterisation of its risk-benefit profile
      compared with those of current and developing regimens for NSCLC should be
      possible once results from several ongoing studies are available. Gemcitabine is
      a valuable new chemotherapy option for patients with advanced pancreatic cancer,
      a disease considered incurable at present. Its apparent survival and palliative
      benefits over fluorouracil require confirmation, but are encouraging, as the need
      to improve both the duration and quality of survival in these patients is well
      recognised.

PMID- 9279510
TI  - Antidiabetic effects of an oral administration of Lactobacillus casei in a non
      insulin-dependent diabetes mellitus (NIDDM) model using KK-Ay mice.
AB  - The antidiabetic effects of Lactobacillus casei (LC) on a non-insulin-dependent
      diabetes mellitus (NIDDM) model, KK-Ay mice, were investigated. The oral
      administration of LC to male 4-week-old KK-Ay mice, or raising the mice on a
      0.05% LC-containing diet significantly decreased the plasma glucose at 8 to 10
      weeks of age compared with the control group. The body weights of the LC-treated
      groups were lower than those of the control group, although the food intake was
      nearly the same in all groups. Phenotypic analysis of spleen cell surface markers
      revealed that the increase in CD4+ T cells at 12 weeks was significantly
      inhibited by the oral treatment with LC. Cytokine production, especially that of
      interferon-gamma and interleukin 2, was also inhibited in the oral LC-treated
      group. The plasma insulin levels of the LC-treated groups were also lower than
      those of the control group, and the insulin binding potential of red blood cells
      in the LC-treated mice was augmented more than that in the control group. Taken
      together, these findings led us to conclude that the oral administration of LC in
      the NIDDM model mice, KK-Ay, was involved in the decrease in the plasma glucose
      level and modified the host immune responses.

PMID- 9279509
TI  - Detection of interleukin 6-producing cells among various organs in normal mice
      with an improved enzyme-linked immunospot (ELISPOT) assay.
AB  - The enzyme-linked immunospot (ELISPOT) assay is an efficient technique for the
      enumeration of single cells secreting antibodies or cytokines. To assess mice
      interleukin 6 (IL-6)-secreting cells at a single cell level, a highly sensitive
      ELISPOT assay with 5-bromo-4-chloro-3-indolylphosphate p-toluidine salt and
      nitroblue tetrazolium chloride (BCIP/NBT) as a gel-substrate has been developed.
      The IL-6 specific ELISPOT assay thus developed with an ordinary plastic ELISA
      plate is as efficient as the previous IL-6 specific ELISPOT assay system which
      uses a nitrocellulose coated plate, and is much more economic and convenient. We
      demonstrated with this newly devised ELISPOT assay that the ratio of IL-6
      producing cells in the resident peritoneal exuded cells was highest in normal
      BALB/c mice, and a few IL-6 secreting cells were detected in all organs we
      tested, namely the spleen, bone marrow, Peyer's patch, axillary lymph node and
      thymus.

PMID- 9279511
TI  - Psychiatric symptoms, bone density and non-specific symptoms in patients with
      mild hypercalcemia due to primary hyperparathyroidism: a systematic overview of
      the literature.
AB  - To determine (1) the relationship between primary hyperparathyroidism with mild
      hypercalcemia and psychiatric disturbances, bone density, or non-specific
      symptoms, and (2) the effect of parathyroidectomy on these outcomes, a systematic
      and critical review of the literature was conducted. Relevant citations were
      identified using MEDLINE (1966 to August, 1995) and PsycINFO (1967 to August,
      1995). Studies were included for the overview if they described patients with
      mild hypercalcemia (< 12 mg/dl), and if they dealt with at least one of the
      following outcomes: psychiatric disturbances, bone density, joint pain,
      constipation, polyuria/nocturia or weight loss. Either a calculated effect size
      or Z score was used to estimate the effect of the disease or parathyroidectomy on
      these outcomes. Seven studies met the inclusion criteria for this overview. Two
      out of three case-control studies on psychiatric symptoms found a significant
      association between primary hyperparathyroidism with mild hypercalcemia and
      psychiatric disturbances (effect sizes; 0.17, 1.2 and 1.6). One of the three
      studies also examined the effect of parathyroidectomy on psychiatric symptoms,
      and found an effect size of 1.5. All four cross-sectional studies that measured
      bone mass showed significantly reduced bone density in the forearm and the lumbar
      spine. The bone loss ranged from 0.9 to 1.4 standard deviation below the age- and
      sex-adjusted mean value in the forearm, and was 0.5 in the spine. There was no
      relevant study regarding non-specific symptoms. Among the seven studies, five did
      not explicitly indicate whether the patients had classical symptoms of either
      osteitis fibrosa cystica or renal stones. Primary hyperparathyroidism with mild
      hypercalcemia is associated with psychiatric disturbances and reduced bone
      density. Nevertheless, further research is needed to determine the symptoms,
      particularly for a group of patients without either classical bone disease or
      renal stones. The effects of parathyroidectomy on these outcomes also remain to
      be determined.

PMID- 9279507
TI  - Lansoprazole. An update of its pharmacological properties and clinical efficacy
      in the management of acid-related disorders.
AB  - Lansoprazole is a proton pump inhibitor that reduces gastric acid secretion. It
      has proved effective in combination regimens for the eradication of Helicobacter
      pylori and as monotherapy to heal and relieve symptoms of gastric or duodenal
      ulcers and gastro-oesophageal reflux. After initial healing, it may be used to
      prevent recurrence of oesophageal erosions or peptic ulcers in patients in whom
      H. pylori is not the major cause of ulceration and to reduce basal acid output in
      patients with Zollinger-Ellison syndrome. Usual dosages are 15 to 60 mg/day,
      although dosages of < or = 180 mg/day have been used in patients with
      hypersecretory states. In patients with duodenal or gastric ulcer, short term
      lansoprazole monotherapy was similar to omeprazole and superior to histamine H2
      receptor antagonists in achieving healing rates > 90%. Lansoprazole was as
      effective a component of H. pylori eradication regimens as omeprazole,
      tripotassium dicitrato bismuthate (colloidal bismuth subcitrate) or ranitidine.
      Lansoprazole was superior to ranitidine in symptom relief and healing of gastro
      oesophageal reflux disease and tended to relieve symptoms more rapidly than
      omeprazole, although initial healing was similar. As maintenance treatment,
      lansoprazole was similar to omeprazole and superior to ranitidine in relieving
      symptoms and preventing relapse. Lansoprazole was also superior to ranitidine in
      healing and relieving symptoms of oesophageal erosions associated with Barrett's
      oesophagus; healing was maintained for a mean of 2.9 years in > or = 70% of
      patients. Lansoprazole was also superior to ranitidine in prophylaxis of
      redilatation of oesophageal strictures. After > or = 4 years of use in patients
      with Zollinger-Ellison syndrome, lansoprazole 60 to 180 mg/day effectively
      controlled basal acid output. Dosages may be reduced in some patients once
      healing and symptom relief has been achieved. Preliminary studies of lansoprazole
      in patients at risk of aspiration pneumonia or stress ulcers show promise.
      Although studies show lansoprazole is potentially effective in treating
      gastrointestinal bleeding, future studies should assess patients' H. pylori
      status. Lansoprazole has been well tolerated in clinical trials, with headache,
      diarrhoea, dizziness and nausea appearing to be the most common adverse effects.
      Tolerability of lansoprazole does not deteriorate with age and the drug is well
      tolerated in long term use (< or = 4 years) in patients with Zollinger-Ellison
      syndrome or reflux disease. Thus, lansoprazole is an important alternative to
      omeprazole and H2 receptor antagonists in acid-related disorders. In addition to
      its efficacy in healing or maintenance treatment, it may provide more effective
      symptom relief than other comparator agents.

PMID- 9279512
TI  - Role of collagen in retinoic acid-induced differentiation and down-regulation of
      TGF-beta receptors in rat preosteoblastic RCT-1 cells.
AB  - Retinoic acid induces differentiation of preosteoblastic cells. We have
      demonstrated that osteoblastic differentiation and down-regulation of
      transforming growth factor (TGF)-beta receptors requires the interaction of type
      I collagen with alpha 2 beta 1 integrin (J Biol Chem 271: 3938-3944, 1996). The
      purpose of this study was to clarify the role of collagen in retinoic acid
      induced differentiation and down-regulation of TGF-beta receptors using
      preosteoblastic RCT-1 cells. Retinoic acid enhanced the expression of alkaline
      phosphatase and type I collagen, and reduced TGF-beta receptors in these cells.
      Inhibiting collagen synthesis abolished these changes. Because TGF-beta inhibits
      osteoblastic differentiation, the changes described here may contribute to the
      osteoblastic differentiation by retinoic acid.

PMID- 9279513
TI  - Effects of p-chlorophenylalanine on male sexual behavior in female rats with
      mesencephalic raphe nuclei lesions.
AB  - The role of serotonergic neurons in the mesencephalic raphe nuclei in regulating
      male sexual behavior in female rats was examined. The median or dorsal raphe
      nucleus lesions (MRL or DRL) were made in ovariectomized rats and behavioral
      tests were performed after implantation of Silastic tubes containing testosterone
      and treatment with serotonin synthesis inhibitor p-chlorophenylalanine (pCPA).
      Half of the animals in each group received 4 100 mg/kg pCPA injections before the
      behavioral test. As a result, the incidences and frequencies of mounts and
      intromissive patterns in the MRL and DRL groups were comparable to those in
      control females without brain surgery. Mount latency in the MRL females was
      shorter than that in the control females. When pCPA was given, most females with
      or without brain surgery showed mounts and intromissive patterns, and frequencies
      were higher than those in females without pCPA. These results suggest that the
      median raphe nucleus plays an inhibitory role in the onset mechanism for
      mounting. On the other hand, a stronger inhibitory influence in regulating male
      sexual behavior exists in other serotonergic neurons than those in the median and
      dorsal raphe nuclei in female rats.

PMID- 9279515
TI  - The results of transsphenoidal surgery for 44 consecutive acromegalic patients.
AB  - A series of 44 patients with acromegaly underwent transsphenoidal surgery between
      1987 and 1996. The early postoperative mean basal GH level < 5 ng/ml or < 3 ng/ml
      was achieved in 43 (97.7%) or 38 (86.4%) out of 44 patients, respectively.
      Preoperative abnormal GH secretory response to TRH, GnRH and oral glucose
      administration was restored to normal both after surgery and at the time of the
      final follow-up in all patients whose early postoperative mean basal GH levels
      were reduced to < 3 ng/ ml, whereas they remained abnormal in those with mean
      basal GH levels of > or = 3 ng/ml. In contrast, insulin-like growth factor 1 (IGF
      1) levels, when measured by the extraction method, tended to be reduced gradually
      to normal between 6 months and 2 years after surgery in some patients with a
      successful operation. Therefore, 34 (87.1%) out of 39 patients who have been
      followed up longer than 6 months met the following stringent criteria at the time
      of the final follow-up: mean basal GH level < 3 ng/ml, a normal IGF-1 level, and
      normal GH response to TRH, GnRH and oral glucose administration. In this series,
      the most unfavorable preoperative factor influencing operative outcome is tumor
      invasion of the cavernous sinus. Our results clearly indicate that selective
      adenomectomy by transsphenoidal surgery is the therapy of first choice in any
      patient with acromegaly and that the complete biochemical cure of acromegaly can
      be achieved in 87% of patients by surgery alone with an acceptable low surgical
      morbidity.

PMID- 9279516
TI  - The stability of truncated epidermal growth factor receptor mRNA is higher than
      that of the full-length receptor mRNA in rat hepatoma cells.
AB  - Truncated and full-length epidermal growth factor (EGF) receptors are produced in
      rat liver cells. The truncated EGF receptor mRNA is almost identical to the full
      length EGF receptor mRNA except for the lack of a 3' region of the full-length
      receptor mRNA. To understand the stability of rat EGF receptor mRNAs, we analyzed
      the expression of EGF receptor mRNAs in the hepatoma cell line, AH66 and liver
      cells. Ten, 7 and 5 kb full-length and 2.7 kb truncated EGF receptor mRNAs were
      detected in both of them. The half-lives of the 10 and 2.7 kb EGF receptor mRNAs
      were determined in AH66 cells using a transcriptional inhibitor, 5,6
      dichlororibofuranosylbenzimidazole. The half-lives of the 10 and 2.7 kb mRNAs
      were 1.2 and 11 h, respectively. These results indicated that the truncated mRNA
      is 4 times more stable than the full-length mRNA in rat cells. As for the
      stability, the role of a sequence of 3'-untranslated region of the EGF receptor
      mRNA was discussed.

PMID- 9279514
TI  - Impaired guanosine 3',5'-cyclic phosphate production in severe pregnancy-induced
      hypertension with high plasma levels of atrial and brain natriuretic peptides.
AB  - To investigate the activation of particulate guanylate cyclase in pregnant women
      with pregnancy-induced hypertension (PIH), plasma levels of atrial natriuretic
      peptide (ANP), brain natriuretic peptide (BNP), and guanosine 3',5'-cyclic
      phosphate (cGMP) were measured by radioimmunoassays specific to each substance.
      Ten normal nonpregnant women, and 30 normal pregnant women, 17 pregnant women
      with mild PIH and 11 pregnant women with severe PIH in the third trimester were
      included in this retrospective observational study. The diagnosis and
      classification of hypertension were carried out according to the technical
      bulletin (No. 91) of the American College of Obstetricians and Gynecologists. In
      the pregnant women with mild PIH, plasma cGMP levels as well as ANP and BNP
      levels were significantly (P < 0.05) higher than those in gestational age-matched
      normal pregnant or nonpregnant women. But in the pregnant women with severe PIH,
      plasma cGMP levels were significantly lower than those in pregnant women with
      mild PIH (P < 0.05), although plasma ANP and BNP levels were higher than those in
      pregnant women with mild PIH.

PMID- 9279517
TI  - Profiles of insulin-like growth factor binding proteins and the protease activity
      in the maternal circulation and its local regulation between placenta and
      decidua.
AB  - Insulin-like growth factors (IGF) and their specific binding proteins (IGFBPs)
      are believed to be important regulators of fetal growth. IGFBP protease which
      proteolyzes IGFBPs and changes the biochemical properties of IGFBPs is also
      presumed to be involved in fetal growth. The aim of this study is to elucidate
      the physiological significance of IGFBP protease in fetal growth and regulators
      of protease in placenta and decidua. The intact IGFBP-3 was proteolyzed into
      fragments when pregnant serum was incubated with 125I-IGFBP-3. IGFBP-3 protease
      activity showed a marked increase at 5 weeks of gestation and reached a plateau
      in maternal circulation at 15 weeks of gestation. These changes in protease
      activity correlated with the profiles of IGFBPs in the maternal circulation
      analyzed by Western ligand blot, where the IGFBP-1 is only the dominant IGFBP.
      The intact IGFBP-3 was proteolyzed when culture media of decidual cells were
      incubated with 125I-IGFBP-3, but was not proteolyzed when culture media of
      trophoblast cells were incubated with 125I-IGFBP-3. Decidual protease activity
      was slightly increased by IGF-I and completely inhibited by progesterone. The
      protease activity was more increased in the mothers with growth retarded infant
      than in those in the mothers with normal growth infants, suggesting that the
      protease activity is elevated in compensation for the impaired fetal growth.
      These results suggest that increased protease activity in maternal blood may be
      involved in the fetal growth indirectly by reducing the binding activity of IGFBP
      3 to IGF-I, and that protease activity in maternal blood may be derived from
      decidua that is regulated by placental hormones.

PMID- 9279518
TI  - Increased circulating levels of insulin-like growth factor-I and decreased
      circulating levels of insulin-like growth factor binding protein-1 in
      postmenopausal women with endometrial cancer.
AB  - In human endometrium insulin-like growth factor binding protein (IGFBP)-1
      inhibits the mitogenic action of insulin-like growth factor (IGF)-I by inhibiting
      the binding of IGF-I to its receptor. Our purpose was to compare circulating
      levels of IGF-I and IGFBP-1 in women with and without endometrial cancer. We
      assessed circulating levels of IGF-I and IGFBP-1 and IGFBP-3 in 23 patients with
      endometrial cancer, 11 patients with uterine cervical cancer and 27 healthy
      control women. The mean circulating level of IGF-I decreased significantly
      following menopause but was not correlated with age in the control group. The
      body mass index was significantly higher in the endometrial cancer group than in
      the control group. Analysis of covariance showed that even after the data were
      adjusted to eliminate the influence of the body mass index, the circulating IGF-I
      concentration was higher in postmenopausal endometrial cancer patients than in
      postmenopausal control subjects. The mean circulating level of IGFBP-1 was
      significantly lower in postmenopausal cancer patients than in postmenopausal
      control subjects. There were no significant differences in the serum levels of
      IGF-I and IGFBP-1 in the patients with cervical cancer and the control group. In
      conclusion, an increased circulating concentration of IGF-I and a decreased
      circulating concentration of IGFBP-1 are associated with endometrial cancer
      especially in postmenopausal women.

PMID- 9279519
TI  - Effects of apolipoprotein E phenotype on serum cholesterol level and cholesterol
      response to diet therapy in patients with hypercholesterolemia.
AB  - We investigated the association of the apolipoprotein (apo) E isoform phenotype
      with the basal serum cholesterol level and cholesterol response to diet therapy
      in outpatients with primary hypercholesterolemia. The basal levels of serum
      cholesterol, triglyceride and HDL-cholesterol in the 132 subjects were 286 +/- 26
      mg/dl, 154 +/- 83 mg/dl and 54 +/- 14 mg/dl, respectively. The frequencies of apo
      E 3/2, 3/3, 4/2, 4/3 and 4/4 were 1, 104, 2, 24 and 1, respectively. There were
      no differences in serum lipids between subjects with the two most common apo E
      phenotypes, i.e., apoE 3/3 (n = 104) and apoE 4/3 (n = 24). The serum cholesterol
      response to diet therapy was evaluated by measuring the serum lipids of 52
      participants before and 2-3 months after diet therapy. After dietary counselling,
      serum cholesterol values were reduced significantly from 293 +/- 27 to 256 +/- 36
      mg/dl (P < 0.01) in the total group of study subjects. There was no significant
      difference in serum cholesterol reduction in response to diet therapy between
      subjects with apoE4 (E4/2, E4/3 and E4/4, n = 12) and without apoE4 (E3/3 and
      E3/2, n = 40). Following dietary counselling, patients who lost a large amount of
      body weight (BM I > or = 1.0) exhibited a greater reduction in serum cholesterol
      than those who showed less weight loss. In conclusion, the results of our study
      demonstrated the primary importance of diet therapy in the treatment of
      hypercholesterolemia, although other investigators have suggested that apo E
      phenotypes influence the response of serum cholesterol to dietary changes.

PMID- 9279520
TI  - Detection of thyroid-stimulating antibody using frozen stocks of Chinese hamster
      ovary cells transfected with cloned human thyrotropin receptor.
AB  - To measure thyroid-stimulating antibody (TSAb) in sera from patients with Graves'
      disease, we developed a new assay system with using frozen stocks of CHO-K1
      cells. CHO-K1 cells transfected with cloned thyrotropin (TSH) receptor on a 96
      well plate were frozen in Cell Banker and stored at -70 degrees C. Three days
      before the assay, they were thawed in the culture medium and allowed to grow in a
      monolayer until use. The medium was replaced with medium containing IgGs from the
      patients, then after 2 h, it was collected and concentrations of adenosine 3'-5'
      cyclicmonophosphate (cAMP) were measured. This method is sensitive enough to
      detect TSAb and it is simpler and easier than the methods which use FRTL-5 cells.

PMID- 9279521
TI  - Dermatitis herpetiformis cured by hormone replacement for panhypopituitarism.
AB  - Dermatitis herpetiformis is an autoimmune skin disorder frequently associated
      with gastrointestinal diseases. We report a 53-year-old male with a four-year
      history of refractory dermatitis herpetiformis associated with hypopituitarism.
      Endocrine testing, ophthalmological examination and magnetic resonance imaging
      revealed hypopituitarism due to a non-functioning pituitary macroadenoma.
      Following transsphenoidal removal of the pituitary tumor and appropriate hormone
      replacement, complete remission of the skin disorder was obtained. We discuss the
      permissive role of panhypopituitarism in the course of dermatitis herpetiformis.

PMID- 9279522
TI  - Homozygous Q258X mutation in the steroidogenic acute regulatory gene in a
      Japanese patient with congenital lipoid adrenal hyperplasia.
AB  - Congenital lipoid adrenal hyperplasia (CLAH) is an autosomal recessive disorder
      characterized by impaired synthesis of all adrenal and gonadal steroid hormones.
      It has recently been reported that mutations in the steroidogenic acute
      regulatory protein (StAR) gene cause CLAH. We analyzed the nucleotide sequences
      of exon 7 of the StAR gene in a Japanese CLAH patient with a karyotype of 47,XYY,
      and her parents. The patient was homozygous for a nonsense mutation Q258X, which
      changed codon 258 (CAG) encoding Gln to the stop codon TAG, and the her parents
      were heterozygous for the Q258X mutation. Since the Q258X mutation destroys a
      MvaI site normally present in the StAR gene sequence, we confirmed the Q258X
      mutation by means of the restriction endonuclease MvaI digestion of the PCR
      products. Endocrinological examinations of the parents revealed normal responses
      of adrenal steroid hormones to exogenous adrenocorticotropin administration,
      confirming the failure to detect the heterozygous carriers of CLAH by hormonal
      evaluation.

PMID- 9279523
TI  - Gestational thyrotoxicosis manifesting as wernicke encephalopathy: a case report.
AB  - The thyroid gland is physiologically stimulated in normal early pregnancy. This
      stimulated thyroid function is occasionally termed "gestational transient
      thyrotoxicosis". The cause of this thyrotoxicosis has been clarified to closely
      it associate with human chorionic gonadotropin (hCG). We encountered a pregnant
      patient with hyperemesis and thyrotoxicosis, who manifested symptoms of Wernicke
      encephalopathy. Although her serum hCG concentration transiently increased in
      accordance with the thyrotoxicosis, it was within normal limits for the
      gestational week. Both the thyrotoxicosis and a catabolic state due to the
      hyperemesis were thought to have induced a vitamin B1 deficiency, causing the
      Wernicke encephalopathy. This case suggests that pregnant patients with
      hyperemesis should undergo careful endocrinological and neurological evaluations.

PMID- 9279524
TI  - Simultaneously found transient hypothyroidism due to Hashimoto's thyroiditis,
      autoimmune hepatitis and isolated ACTH deficiency after cessation of
      glucocorticoid administration.
AB  - We present a 42-year-old woman with concomitant transient hypothyroidism due to
      Hashimoto's thyroiditis, autoimmune hepatitis and isolated ACTH deficiency. Two
      months after ceasing prednisolone (5 mg/day) for uveitis, she was discovered
      incidentally to have liver dysfunction with hypergammaglobulinemia, later
      diagnosed as autoimmune hepatitis by histological examination of the biopsied
      liver. In addition, primary hypothyroidism due to Hashimoto's thyroiditis and
      secondary hypocortisolism due to isolated ACTH deficiency were revealed by
      endocrinological examination. Although not treated, her liver dysfunction and
      hypothyroid state recovered simultaneously, and the isolated ACTH deficiency was
      restored six months later. We concluded, after a needle-biopsy of the thyroid,
      that the transient hypothyroidism was due to Hashimoto's thyroiditis and the
      reversible ACTH deficiency was probably due to autoimmune hypophysitis. This case
      shows that cessation of steroid treatment may transiently exacerbate the
      polyglandular autoimmune syndrome.

PMID- 9279525
TI  - Somatostatin receptor subtype gene expression in human endocrine gastroentero
      pancreatic tumours.
AB  - Somatostatin and its analogues are now of current use in the management of
      endocrine gastroentero-pancreatic (GEP) tumours for the purpose of inhibiting
      hormone hypersecretion, carrying scintigraphy imaging and attempting to slow down
      tumour growth. Recent molecular studies have revealed the existence of up to five
      membrane somatostatin receptor subtypes termed SSTR1-5. However, whether or not
      scintigraphy imaging and tumour characteristics are correlated with specific
      subtype(s) remains unclear. SSTR1-5 messenger RNA (mRNA) transcripts were
      investigated in 38 endocrine GEP tumours (32 islet cell tumours, six carcinoid)
      using reverse transcriptase polymerase chain reaction (RT-PCR), and their
      distribution was analysed with respect to tumour characteristics and scintigraphy
      imaging. SSTR2, SSTR5 and SSTR4 were detected in most cases of endocrine GEP
      tumours (92%, 84%, and 82% respectively), but SSTR1 and SSTR3 were less
      frequently observed (66% and 50% respectively). No clear-cut correlation was
      found between tumour characteristics and subtype mRNA distribution. Moreover, no
      differences in mRNA subtype distribution were found between the 17 tumours
      detected by scintigraphy and the four tumours not detected by this method.
      Somatostatin receptor mRNA subtypes are widely expressed in endocrine GEP
      tumours, but their distribution is not correlated with tumour characteristics or
      scintigraphy positivity.

PMID- 9279526
TI  - Somatostatin receptor subtype expression in human tissues: a prediction for
      diagnosis and treatment of cancer?

PMID- 9279527
TI  - Increased expression of CD11b/CD18 on phagocytes in ischaemic disease: a bridge
      between inflammation and coagulation.
AB  - The aim of this study was to assess the expression of CD11b/CD18 integrin
      adhesion molecules on the phagocytes of patients with ischaemic diseases, and to
      evaluate the concentration of soluble adhesion molecules that are released from
      endothelium (sICAM-1) and from phagocytes (sL-selectin). A total of 370 patients
      were enrolled: 120 with coronary artery disease (CAD); 50 with peripheral artery
      occlusive disease (PAOD); and 200 control subjects with no clinical
      manifestations of ischaemic disease. CD11b/CD18 integrin was detected by flow
      cytometry, whereas sL-selectin and sICAM-1 concentrations were detected using a
      sandwich-type immunoassay. CD11b/CD18 integrin expression was found to be higher
      in the patients with ischaemic disease than in the control subjects (P < 0.001).
      The PAOD patients had higher values of CD11b/CD18 integrin than the CAD ones (P <
      0.01). The concentration of soluble adhesion molecules did not show any
      significant differences within the three groups (P = NS). The high expression of
      CD11b/CD18 integrin in ischaemic disease patients may depend on the increased,
      but probably stable, cytokine network that has been demonstrated to occur in
      chronic ischaemic diseases: the difference observed between PAOD and CAD patients
      could be the consequence of higher inflammatory activation probably resulting
      from the greater extent of the atherosclerotic process in PAOD, or of the more
      localized ischaemic area in CAD patients. CD11b/CD18 can therefore be considered
      a marker of chronic phagocyte activation during ischaemic disease. On the other
      hand, sICAM and sL-selectin concentrations were found to be within the normal
      range; they have recently been considered as a marker for acute ischaemic events
      and acute inflammatory process activation. Our results confirm that in
      uncomplicated atherosclerosis no acute inflammatory process activation should
      occur.

PMID- 9279528
TI  - Impaired gallbladder and gastric motility and pathological gastro-oesophageal
      reflux in gallstone patients.
AB  - Impaired gallbladder motility is common in gallstone patients and might be
      associated with other gastrointestinal defects. Twenty patients with small stones
      in an opacified gallbladder at oral cholecystography and 20 healthy subjects
      homogeneous for sex, age and body size were studied by ultrasonography to assess
      gallbladder and gastric emptying simultaneously in response to a standard liquid
      meal (120 kcal, 11 g fat, 200 mL). The same subjects underwent ambulatory 24-h
      gastro-oesophageal pH monitoring. Dyspeptic symptoms were specifically
      investigated using a questionnaire. Gallstone patients had a significantly larger
      fasting (P < 0.05) and residual (P < 0.005) gallbladder volume with slower (P <
      0.05) and less complete (ANOVA, 0.001 < P < 0.05) gastric emptying than healthy
      control subjects. The speed of antral emptying was significantly correlated with
      the speed of gallbladder emptying (n = 40, r = +0.31, P < 0.05). Pathological
      gastro-oesophageal reflux was present in 75% and 15% of patients and control
      subjects respectively (P < 0.05). Overall, 95% of gallstone patients had abnormal
      pH profiles resulting from pathological gastro-oesophageal reflux and/or
      prolonged gastric alkalinization. The speed of post-prandial antral emptying was
      significantly correlated with the duration of the longest gastro-oesophageal
      reflux episode (r = +0.30, P < 0.03) and duodeno-gastric reflux episode (r =
      +0.80, P < 0.02). Best predictors for gastric alkalinization were the following
      indices of gallbladder function: large fasting volume (P = 0.03), large ejection
      volume (P = 0.009) and slower emptying (P = 0.032). Gallbladder and gastric
      motility were similar in patients with (n = 12) and without (n = 8) dyspeptic
      symptoms. Pathological gastro-oesophageal reflux was found in 83% of dyspeptic
      patients and in 25% of patients without dyspepsia (P < 0.01). When reflux was
      present, it was significantly less in asymptomatic than in dyspeptic patients
      [time at pH < 4, median (range): 6.4% (3.2-22.6%) vs. 47.8% (2.1-87%), P < 0.05].
      This study shows that a subgroup of gallstone patients with small-mainly
      asymptomatic-stones have impaired gallbladder and gastric motility as well as
      abnormal gastro-oesophageal pH-profiles. These findings point to the existence of
      multiple functional defects of the upper gastrointestinal tract in gallstone
      disease.

PMID- 9279529
TI  - Effect of elevated serum prolactin concentrations on the immunophenotype of human
      lymphocytes, mitogen-induced proliferation and phagocytic activity of
      polymorphonuclear cells.
AB  - It has been suggested that the immune system is an important target tissue of
      prolactin (PRL). We therefore investigated several immune parameters in nine
      patients with chronically elevated serum prolactin concentrations. The
      immunophenotype of lymphocytes, mitogen-induced lymphocyte proliferation and
      phagocytic activity of polymorphonuclear cells were determined under high serum
      prolactin levels and 2 weeks after treatment with dopamine agonists. An increased
      CD4/CD8 ratio in the hyperprolactinaemic patients could be detected compared with
      healthy control subjects, which remained high after treatment and did not seem to
      correlate with serum prolactin concentrations. Peripheral blood B lymphocytes
      showed an increased expression of CD69 in the treated group but not in untreated
      patients compared with healthy control subjects. Interleukin 2 receptor, CD45RO,
      transferrin receptor or HLA-DR expression of CD4 or CD8 cells, as well as
      oxidative burst and phagocytic activity of granulocytes, were not affected in the
      patients with prolactinomas. Lymphocyte transformation response to
      phytohaemagglutinin in vitro was found not to be influenced by elevated prolactin
      levels except at the highest mitogen concentration tested. These data together
      with previous reports suggest that, although PRL is required for lymphocyte
      maturation to achieve normal immune function, elevated PRL levels do not lead to
      an 'overstimulation' of the immune system in men.

PMID- 9279530
TI  - Antibodies to mycobacterial 65-kD heat shock protein cross-react with the main
      mitochondrial antigens in patients with primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease associated
      with autoimmune disorders. The aetiology is unknown, although it has been
      suggested that the disease may be related to infectious agents. Previous studies
      revealed that sera from patients with PBC react against Mycobacterium gordonae.
      This specific reactivity, characterized by a recognition of two membrane
      polypeptides of 70-65 and 55 kD, cross-react with the two major mitochondrial
      autoantigens of PBC. As the most immunogenic components of mycobacteria are the
      heat shock proteins (hsp), which have been associated with autoimmunity, this
      study has been undertaken to characterize whether the reacting polypeptides in
      PBC are hsp from M. gordonae. Cultures of M. gordonae were incubated at 37
      degrees C and 46 degrees C before sonication, protein extraction and separation
      by SDS-PAGE. Exposure of M. gordonae to heat shock treatment resulted in membrane
      protein overexpression, similar to the 70-65-kD polypeptide recognized by the
      sera from patients with PBC. Immunoprecipitation assays with a monoclonal
      antibody directed against the Hsp65 kD of mycobacteria and with sera from
      patients with PBC revealed similar reacting profiles characterized by the
      precipitation of the overexpressed 65-kD polypeptide from M. gordonae.
      Competitive immunoblotting showed that binding of the monoclonal antibody to the
      Hsp65 kD protein was prevented by preincubation with sera from patients with PBC,
      but not with sera from healthy subjects. Furthermore, monoclonal antibody to the
      Hsp65 kD protein recognized the main mitochondrial autoantigens of PBC (PDH-E2
      and BCKDH-E2). These data indicate the existence of cross-reacting epitopes
      contained on M. gordonae Hsp65 kD and the main mitochondrial antigens in patients
      with PBC.

PMID- 9279531
TI  - Comparative effects of nitric oxide synthesis inhibition and catecholamine
      treatment in a rat model of endotoxin shock.
AB  - Catecholamines and volume repletion are currently used for the treatment of
      septic shock. However, the prognosis of patients suffering from this condition is
      very poor. An overproduction of nitric oxide (NO) seems to be related to the
      hypotension and tissue damage of endotoxin shock. Thus, treatment with NO
      synthase inhibitors has been proposed. Using a rat model of septic shock we have
      studied the effects of noradrenaline or the NO synthase inhibitor, NG-nitro-L
      arginine methylester (L-NMMA) on arterial pressure, tissue damage and NO
      production. Anaesthetized rats treated with Salmonella typhosa showed a decrease
      in blood pressure accompanied by an increase in the plasma concentration of
      cytosolic enzymes (transaminases and lactate dehydrogenase, markers of cell
      disruption) and nitrite plus nitrate (NO2-/NO3-, markers of NO production). A
      large proportion of these animals (40%) died before the end of the experiment. Co
      treatment with noradrenaline resulted in temporary maintenance of arterial
      pressure followed by a decline, despite the dose being increased progressively.
      No differences were observed in plasma cytosolic enzymes, NO2-/NO3- or mortality
      compared with animals treated with lipopolysaccharide (LPS) alone. In contrast,
      administration of L-NMMA (10 mg kg-1) to septic animals prevented the fall in
      blood pressure and death caused by endotoxin. This treatment markedly diminished
      cell disruption, as measured by the plasma levels of necrosis enzymes, and
      partially, but significantly, reduced the production of NO as assessed by plasma
      NO2-/NO3-. We conclude that tissue damage in septic shock is related to the
      overproduction of NO and not exclusively to the hypotension that follows this
      increased production. Thus, maintenance of blood pressure with catecholamines
      fails to improve cellular damage. Instead, partial inhibition of NO generation is
      sufficient to ameliorate the haemodynamic and tissue-damaging effects of septic
      shock and improves survival in this model of endotoxaemia.

PMID- 9279532
TI  - Vasoactive substances in early dumping syndrome: effects of dumping provocation
      with and without octreotide.
AB  - In patients after gastric surgery, early dumping symptoms can be provoked by oral
      glucose challenge. Octreotide effectively prevents the occurrence of dumping
      symptoms. We have studied plasma renin activity (PRA), aldosterone and atrial
      natriuretic peptide (ANP) concentrations in nine patients with early dumping, 10
      surgical control subjects and nine healthy control subjects after an oral glucose
      challenge preceded by either placebo or 25 micrograms of octreotide
      subcutaneously (s.c.). In the dumping group, basal PRA was significantly (P <
      0.01) higher (3.9 +/- 0.6 micrograms L-1 h-1) than in either surgical or healthy
      control subjects (1.1 +/- 0.3 micrograms L-1 h-1 and 1.1 +/- 0.2 micrograms L-1 h
      1 respectively) and showed a significant rise after glucose ingestion to 5.4 +/-
      0.9 micrograms L-1 h-1 that did not occur in control subjects. Aldosterone
      concentration showed a concomitant rise. In dumping patients, plasma ANP
      decreased after glucose ingestion from 31 +/- 6 ngL-1 to 21 +/- 5 ngL-1 (P <
      0.05). This decrease did not occur in control subjects. Early dumping is
      associated with an activation of the renin-aldosterone axis and a decrease in
      plasma ANP, reflecting a hypovolaemic state. Octreotide prevents the occurrence
      of these changes.

PMID- 9279533
TI  - Effect of glibenclamide on insulin release at moderate and high blood glucose
      levels in normal man.
AB  - Insulin release occurs in two phases; sulphonylurea derivatives may have
      different potencies in stimulating first- and second-phase insulin release. We
      studied the effect of glibenclamide on insulin secretion at submaximally and
      maximally stimulating blood glucose levels with a primed hyperglycaemic glucose
      clamp. Twelve healthy male subjects, age (mean +/- SEM) 22.5 +/- 0.5 years, body
      mass index (BMI) 21.7 +/- 0.6 kgm-2, were studied in a randomized, double-blind
      study design. Glibenclamide 10 mg or placebo was taken before a 4-h
      hyperglycaemic clamp (blood glucose 8 mmol L-1 during the first 2 h and 32 mmol L
      1 during the next 2 h). During hyperglycaemic clamp at 8 mmol L-1, the areas
      under the delta insulin curve (AUC delta insulin, mean +/- SEM) from 0 to 10 min
      (first phase) were not different: 1007 +/- 235 vs. 1059 +/- 261 pmol L-1 x 10 min
      (with and without glibenclamide, P = 0.81). However, glibenclamide led to a
      significantly larger increase in AUC delta insulin from 30 to 120 min (second
      phase): 16087 +/- 4489 vs. 7107 +/- 1533 pmol L-1 x 90 min (with and without
      glibenclamide respectively, P < 0.03). The same was true for AUC delta C-peptide
      no difference from 0 to 10 min but a significantly higher AUC delta C-peptide
      from 30 to 120 min on the glibenclamide day (P < 0.01). The M/I ratio (mean
      glucose infusion rate divided by mean plasma insulin concentration) from 60 to
      120 min, a measure of insulin sensitivity, did not change: 0.26 +/- 0.05 vs. 0.22
      +/- 0.03 mumol kg-1 min-1 pmol L-1 (with and without glibenclamide, P = 0.64).
      During hyperglycaemic clamp at 32 mmol L-1, the AUC delta insulin from 120 to 130
      min (first phase) was not different on both study days: 2411 +/- 640 vs. 3193 +/-
      866 pmol L-1 x 10 min (with and without glibenclamide, P = 0.29). AUC delta
      insulin from 150 to 240 min (second phase) also showed no difference: 59623 +/-
      8735 vs. 77389 +/- 15161 pmol L-1 x 90 min (with and without glibenclamide, P =
      0.24). AUC delta C-peptide from 120 to 130 min and from 150 to 240 min were
      slightly lower on the glibenclamide study day (both P < 0.04). The M/I ratio from
      180 to 240 min did not change: 0.24 +/- 0.04 vs. 0.30 +/- 0.07 mumol kg-1 min-1
      pmol L-1 (with and without glibenclamide, P = 0.25). In conclusion, glibenclamide
      increases second-phase insulin secretion only at a submaximally stimulating blood
      glucose level without enhancement of first-phase insulin release and has no
      additive effect on insulin secretion at maximally stimulating blood glucose
      levels. Glibenclamide did not change insulin sensitivity in this acute
      experiment.

PMID- 9279534
TI  - Effects of low-dose L-arginine on insulin-mediated vasodilatation and insulin
      sensitivity.
AB  - The present study was carried out to evaluate the effect of a low-dose
      intravenous supplementation of L-arginine on insulin-mediated vasodilatation and
      insulin sensitivity. The study was performed in healthy subjects (n = 7) and
      patients with obesity (n = 9) and non-insulin-dependent diabetes mellitus (NIDDM)
      (n = 9). Insulin-mediated vasodilatation was measured by venous occlusion
      plethysmography during the insulin suppression test, evaluating insulin
      sensitivity. Experiments were performed twice in each subject in the presence or
      absence of a concomitant infusion of L-arginine (0.52 mg kg-1 min-1). L-Arginine
      restored the imparied insulin-mediated vasodilatation observed in obesity (22.4
      +/- 4.1%, P < 0.01 vs. without L-arginine) and NIDDM (20.3 +/- 3.2%, P < 0.01 vs.
      without L-arginine). In healthy subjects, no effect on insulin mediated
      vasodilatation was observed (24.8 +/- 3.1% vs. 21.4 +/- 3.1%). Insulin
      sensitivity was improved significantly (P < 0.001) in all three groups by
      infusion of L-arginine. No effect of L-arginine was observed on insulin, insulin
      like growth factor I (IGF-I), free fatty acids (FFAs) or C-peptide levels during
      the insulin suppression test. Our data indicate that defective insulin-mediated
      vasodilatation in obesity and NIDDM can be normalized by intravenous L-arginine.
      Furthermore, L-arginine improves insulin sensitivity in obese patients and NIDDM
      patients as well as in healthy subjects, indicating a possible mechanism that is
      different from the restoration of insulin-mediated vasodilatation.

PMID- 9279535
TI  - alpha 1-Antitrypsin (AAT) deficiency and ANCA-positive systemic vasculitis:
      genetic and clinical implications.
AB  - A high incidence of alpha 1-antitrypsin (AAT) deficiency has been reported in
      patients with C-ANCA systemic vasculitis in association with antibodies against
      proteinase-3 (PR3). To clarify the role of AAT deficiency in the acute vasculitic
      process as well as in progression of the disease, we studied 84 patients with
      either C-ANCA or P-ANCA vasculitis with special reference to: (a) the AAT gene,
      (b) the phenotypic (Pi) variants and (c) the serum levels during both acute
      illness and remission. The PiZ gene was found in six patients (8% vs. 1.5%
      controls) irrespective of the type of autoantibodies (C-ANCA vs. P-ANCA). All PiZ
      patients displayed the ability to raise their AAT serum levels up to the normal
      range during acute illness. In contrast, 24 patients with the PiM phenotype
      presented low AAT serum levels during acute illness. In all these patients, the
      AAT levels returned to normal values during the remission. Low AAT levels were
      associated with low levels of C-reactive protein (PCR) (P < 0.001), with a less
      severe renal involvement or a minor risk of death, and, in one tested patient,
      with a novel point mutation (TCGA-->TCAA) at the enhancer-promoter region of the
      AAT gene. Low AAT serum levels did not correlate with either type/titre of
      autoantibody or distribution/severity of the vasculitis process. In the case
      control study, high AAT levels emerged as a major determinant of progression
      towards end-stage renal failure [odds ratio 3 (95% CI 1.1-8.4)]. These results
      indicate: (a) a high incidence of the PiZ gene of AAT in systemic vasculitis
      irrespective of the type of autoantibodies; (b) a novel form of AAT deficiency
      associated with the normal PiM phenotype becoming manifest only during acute
      illness; (c) dysregulation of the acute-phase response affecting selectively AAT
      or both AAT and PCR; (d) correlation between low plasma levels of AAT and less
      severe renal involvement or risk of death.

PMID- 9279536
TI  - Is the effect of acute hyperglycaemia on interdigestive antroduodenal motility
      and small-bowel transit mediated by insulin?
AB  - Acute hyperglycaemia inhibits antroduodenal motility. In non-diabetic subjects
      this inhibitory effect may result from reactive endogenous hyperinsulinaemia.
      Therefore, we investigated the effects of hyperinsulinaemia during both
      hyperglycaemia and euglycaemia on interdigestive antroduodenal motility
      (perfusion manometry) and duodenocaecal transit time (DCTT; lactulose breath-H2
      test). Six healthy volunteers (age 20-26 years) were studied for 240 min on three
      separate occasions in random order during: (a) i.v. saline (control); (b) acute
      hyperglycaemic hyperinsulinaemia (HG) with plasma glucose at 15 mmolL-1; and (c)
      euglycaemic hyperinsulinaemia (HI) with plasma insulin at 80 mUL-1 and glucose at
      4-5 mmolL-1, RESULTS: DCTT was significantly (P < 0.05) prolonged during HG (158
      +/- 23 min) compared with control (95 +/- 25 min), whereas HI had no effect (100
      +/- 17 min). Mean duration of complete migrating motor complex (MMC) cycles was
      significantly (P < 0.05) reduced during HG (63 +/- 9 min) compared with control
      (103 +/- 15 min) and HI (105 +/- 16 min), which resulted from a significantly (P
      < 0.05) shorter duration of phase II. Antral motility was significantly (P <
      0.05) reduced during both HI (20 +/- 8 contractions 240 min-1) and HG (9 +/- 5)
      compared with control (43 +/- 7). It is concluded that in healthy subjects
      hyperglycaemia prolongs DCTT, increases duodenal MMC cycle frequency and inhibits
      antral motility. Hyperinsulinaemia reduces antral motor activity but has no
      effect on interdigestive duodenal motility or DCTT. Thus, other factors, apart
      from insulin, mediate the inhibitory effect of hyperglycaemia on interdigestive
      intestinal motility and transit.

PMID- 9279537
TI  - Classification of complex regional pain syndromes. New concepts.
AB  - A new classification system, termed complex regional pain syndromes types I and
      II, has been devised to replace the nomenclature of pain disorders previously
      termed reflex sympathetic dystrophy and causalgia. CRPS type I does not have
      identifiable major nerve injury, whereas CRPS type II has an identifiable major
      nerve injury. The classification is based on clinical symptoms and signs without
      incorporating any mechanistic connotations. These CRPS disorders may have SMP,
      SIP, or both.

PMID- 9279538
TI  - Algodystrophy. A spectrum of disease, historical perspectives, criteria of
      diagnosis, and principles of treatment.
AB  - Algodystrophy describes a group of extremely polymorphic pathological
      manifestations caused by vasomotor disturbances. Clinical expressions of
      algodystrophy are summarized, and principles of treatment are discussed.

PMID- 9279539
TI  - Reflex sympathetic dystrophy of the upper extremity. Clinical features and
      response to multimodal management.
AB  - The weight of available evidence suggests that reflex sympathetic dystrophy (RSD)
      is a complex clinical entity that (1) occurs predominantly in young adult women;
      (2) has five clinical types but presents most frequently as minor traumatic
      dystrophy; (3) has primary signs and symptoms (e.g., pain, edema, stiffness, and
      discoloration) that are expressed highly in each clinical type, whereas secondary
      signs and symptoms are variable; (4) responds well to treatment, regardless of
      its clinical type; and (5) is managed best when treatment is started early. It
      can be concluded that RSD is a multifaceted disease that responds well when
      managed with a multimodal treatment program aimed at the various interacting
      components of the disorder. The recognition and documentation of the variation of
      the clinical features of RSD may allow for its earlier diagnosis and treatment
      and thus significantly improve the chances for a successful outcome.

PMID- 9279540
TI  - Somatic versus sympathetic mediated chronic limb pain. Experience and treatment
      options.
AB  - It has been helpful in our practice to separate somatic from sympathetic-mediated
      peripheral nerve pain. We would recommend application of the new nomenclature of
      type I complex regional pain (sympathetic dystrophy) and type II complex regional
      pain (causalgia) (see Table 1). We believe it is essential that both of these
      conditions be separated into their early and late phases and that the treatment
      alternatives be customized for the individual patient and the peripheral nerve
      involved. If a cast, pin, or external fixation apparatus is associated with
      peripheral nerve pain, the offending apparatus must be removed immediately and
      other forms of treatment initiated for the underlying injury. For acute injury
      and postsurgical pain, narcotic pain medications should be used no longer than 72
      hours and careful patient re-examination must be performed if pain persists.
      Prescription of narcotic pain medications on a continuing basis is often the
      primary reason for the development of chronic pain syndromes. Physical therapy
      for the patient with chronic peripheral limb pain must be performed in a pain
      free environment. "No pain, no gain" does not apply in the treatment of chronic
      limb pain-rather the reverse: "Only gain with no pain." In differentiating
      between sympathetic pain and somatic pain, the use of the reflex sympathetic
      dystrophy (RSD) score can be helpful (Table 4). If the pain is somatic, treatment
      options include: Somatic Pain: Treatment Isolated nerve block Continuous nerve
      block TENS (external) Direct electrical nerve stimulation (internal) Nerve
      ablation If the pain is sympathetic in origin, treatments to be considered are:
      Sympathetic Nerve Pain: Treatment Protection of limb (garment or splint) Combine
      with active use Sympathetic blocks single continuous Sympathectomy In addition,
      the treatment of each of those conditions must be directed at the primary
      condition. Once the two conditions are separated, a careful program of pain
      management is required. In patients who present with late pain dysfunction, the
      more commonly observed phenomenon at our institution, the combination of
      physician, surgeon, and anesthesiologist is essential. The role of physical
      therapist in restoring function to the injured limb must be discussed and planned
      carefully. Initial pain management is organized through a qualified
      anesthesiologist dedicated to this field. Physical therapy follows but only in a
      pain-free environment. The surgeon's role is to assist and direct the pain
      management program. Surgeons can be involved in the placement of percutaneous
      catheters, as well as isolated peripheral nerve blocks. Surgical intervention is
      limited to the release of compressive neuropathies, nerve transfers, and
      revascularization of the peripheral nerve bed. The surgeon occasionally may be
      involved in the manipulation and pinning of contracted joints, as well as release
      of muscle or joint contractures, followed by a supervised program of early range
      of motion. Finally, it is important that both physician and surgeon serve as
      patient advocates when questions of workers' compensation intervene that could
      deter proper treatment programs or when the patient needs the encouragement and
      guidance to continue with treatments that don't always initially appear to have
      immediate results. Finally, requests to the surgeon to find an operative cure
      must be resisted while continued psychological encouragement is provided.

PMID- 9279541
TI  - Psychological aspects of algodystrophy.
AB  - It is important to attempt to classify the symptoms of algodystrophy at an
      epidemiologic level to assess the effective contribution of the psychological
      element. This article discusses a personal approach to dealing with the
      psychological aspects of algodystrophy.

PMID- 9279542
TI  - Post-traumatic upper extremity reflex sympathetic dystrophy. Clinical course,
      staging, and classification of clinical forms.
AB  - RSD is a symptom complex, representing an exaggerated response to injury or
      tissue damage. The amplification of the normal responses probably occurs both in
      the periphery and in the central nervous system. Diagnostic criteria are still
      under discussion, and treatment modalities are still directed toward the symptoms
      because the pathophysiology is not known. The pain of the condition may be
      sympathetically maintained of sympathetically independent (or both), and
      sympathetic blockade is useful in the former category. Treatment modalities must
      be directed toward optimizing both comfort and function of the affected
      extremity. Such treatment programs might occur in a multidisciplinary setting.

PMID- 9279543
TI  - Reflex sympathetic dystrophy. An exaggerated regional inflammatory response?
AB  - Reflex sympathetic dystrophy (RSD) is a syndrome affecting an extremity after a
      minor trauma or operation. Currently, there is no consensus about the
      pathogenesis of RSD. The authors performed various clinical and experimental
      investigations, including studies of the effects of anti-inflammatory treatment,
      that support the hypothesis that RSD is the result of an exaggerated inflammatory
      response to injury or surgery.

PMID- 9279544
TI  - Stenosis of the subclavian vein. An unknown cause of resistant reflex sympathetic
      dystrophy.
AB  - The striking similarity of certain pain symptoms and neurologic changes in RSD
      and the findings of severe thoracic outlet and inlet syndrome were the reason why
      clinical diagnostic studies of this dystrophy were also completed by radiologic
      examinations of the vessel system. Surprisingly, more or less striking and
      differently configurated stenoses in the area of the subclavian vein, with a
      resulting impairment of the venous run-off, were found. Those findings have been
      documented in 20 of 21 patients with RSD since 1984 by functional venography and,
      in the meantime, they were confirmed intraoperatively in nine resistant cases.
      The stenoses led to a lesion-caused disproportion between increased arterial
      inflow and decreased venous outflow, with venous stasis. Consequently, they acted
      as a primary cause of an edema of the hand, with corresponding regional results,
      mainly on the function of the sympathetic nervous system. That shows a primarily
      increased activity in RSD that under the influence of local factors results in a
      pathologic positive feedback mechanism, as already was known. The stenosis of the
      subclavian vein, in my opinion, is the long-searched for cause of the so-called
      "individual predisposition." The use of functional venogram in diagnosis is
      essential because it gives important hints at the diagnostic and prognostic
      outlook for a possible surgical treatment of resistant RSD. It is also very
      important in understanding the pathogenesis. To improve the venous flow and
      diminish or interrupt the sympathetic efferences, we performed transaxillary
      decompression of the neurovascular bundle with additional upper thoracic
      sympathectomy in resistant cases of RSD. Nine patients experienced immediate
      improvement of the pain syndrome and edema, as well as the entire postoperative
      course. After an average follow-up of 7.5 years, we found an excellent result in
      seven patients, a good result in one, and a fair result in one. Intraoperative
      findings and the arteriograms we performed on seven surgically treated patients
      indicate the primarily increased sympathetic activity in RSD is mainly caused by
      irritations and compressions of the lower plexus roots as well as the
      postganglionic fibers in the area of the subclavian artery, mainly by the inner
      rim of the first rib and fibromuscular structures. So the two main pathogenetic
      factors of RSD are known, and now can be localized and documented radiologically.
      It now should be possible to study the pathophysiology of RSD in an appropriate
      animal model.

PMID- 9279545
TI  - Infrequent presentations of reflex sympathetic dystrophy and pseudodystrophy.
AB  - Pseudodystrophy is a condition that in the past was regarded incorrectly as a
      kind of reflex sympathetic dystrophy. The difference between both diseases can be
      ascertained easily by a bone scintigraphy. Other clinical features of
      pseudodystrophy are discussed. Infrequent presentations of reflex sympathetic
      dystrophy are described: radial, parcellar, and zonal cases; vertebral
      localization; and other misleading conditions.

PMID- 9279546
TI  - Clinical value of dynamic bone and vascular scintigraphy in diagnosing reflex
      sympathetic dystrophy of the upper extremity.
AB  - The role of planar dynamic scintigraphy in the diagnosis and staging of reflex
      sympathetic dystrophy (RSD) is presented. Bone and vascular tracers are used for
      this purpose. The bone scan assessment corresponded closely to the clinical
      diagnosis and appeared excellent to exclude RSD. Accurate staging is important
      for therapy decisions. Staging by the early phases of bone and vascular scans
      were concordant in about three quarters of patients, but vascular scintigraphy
      led to a restaging in the remaining quarter of patients. Both scintigraphic
      procedures (bone and vascular) are indicated in diagnosing and monitoring upper
      extremity RSD.

PMID- 9279548
TI  - Physical modalities for complex regional pain syndrome.
AB  - Hand therapy is the backbone of a treatment program for complex regional pain
      syndrome. Various treatment techniques and physical modalities are described in
      the framework of a clear set of treatment goals. Hand therapy is often the only
      treatment necessary for simple cases. Adjunct treatments, such as injections or
      other pharmacologic agents, may be needed when pain control is problematic.

PMID- 9279547
TI  - Imaging in reflex sympathetic dystrophy.
AB  - The diagnosis of reflex sympathetic dystrophy (RSD) relies on clinical
      evaluation, scintigraphy or MR imaging, and routine radiographs. Because RSD has
      variable manifestations with a strong psychogenic overlap, it is desirable to
      have a noninvasive test to determine the presence of RSD to allow for appropriate
      treatment. MR imaging allows a differential diagnosis between RSD and other bone
      lesions. It proves to be a reliable technique in showing and characterizing RSD
      better than radiographic examination and radionuclide study.

PMID- 9279549
TI  - Can algodystrophy be prevented after hand surgery?
AB  - Algodystrophy is characterized initially by an increase in arterial flow, an
      increase in blood pool, a decrease in microcirculatory velocity, and a loss of
      thermoregulatory control. These changes, producing the typical symptomatology,
      associated diffuse hand pain, diminished hand function, edema, and abnormal color
      and temperature, are believed now to correspond in most cases to an exaggeration
      of the normal post-traumatic inflammatory responses and are not the consequence
      of sympathetic damage. Algodystrophy may be prevented in most hand surgery
      patients by minimizing the normal postoperative inflammation, by increasing
      venous return (especially by avoiding plaster casts and constrictive dressings),
      by controlling post-traumatic pain, by promoting early active mobilization, and
      by reassuring the patient. If there is any sign of algodystrophy, three-phase
      bone scintigraphy should be obtained and treatment instituted immediately.

PMID- 9279550
TI  - Medical treatment of reflex sympathetic dystrophy.
AB  - The treatment of reflex sympathetic dystrophy is not delineated clearly, and
      there are few controlled studies regarding rehabilitation as medicine.
      Analgesics, nonsteroidal anti-inflammatory drugs, and intra-articular steroids
      are used widely, but especially in Europe, calcitonin is the primary treatment at
      early stages of the disease. Local intravenous injections are used currently in
      case of failure of the previous treatments. Physical therapy and rehabilitation
      are needed also to decrease pain and to improve stiffness.

PMID- 9279551
TI  - Somatic or sympathetic block for reflex sympathetic dystrophy. Which is
      indicated?
AB  - Patients with reflex sympathetic dystrophy (complex regional pain syndromes) are
      often referred to pain medicine physicians for assistance in providing pain
      control during rehabilitation of their painful upper extremity. When deciding
      which pain control technique to use in an individual patient, physicians must
      consider both somatic and sympathetic blocks. Each of these nerve blocks has
      advantages and disadvantages that may be tailored to an individual patient's pain
      state and rehabilitation program to optimize recovery.

PMID- 9279552
TI  - Regional intravenous sympathetic nerve blocks.
AB  - The assessment of the possible efficacy of regional intravenous blocks or
      sympathetic blocks, in general, raises a number of questions that may be answered
      after studying the techniques of regional pharmacologic segmental blocks and
      their effects on the sympathetic system. The authors present an original clinical
      study evaluating the capacity of regional intravenous guanethidine to induce a
      sympathetic blockade compared with other techniques.

PMID- 9279553
TI  - Electrical stimulation and the treatment of complex regional pain syndromes of
      the upper extremity.
AB  - Clinical, intractable pain in the upper extremity often results from neuroma,
      direct injury to a peripheral nerve, or repetitive operative insults to a
      peripheral nerve that has compressive neuropathy. Electrical stimulation applied
      directly to a single peripheral nerve can provide sufficient relief of pain,
      improve patient outlook, improve lasting sleep, release the individual from
      addictive narcotic pain medication, and restore a psychological sense of well
      being.

PMID- 9279554
TI  - Confocal analysis of the molecular heterogeneity in the pericellular
      microenvironment produced by adult canine chondrocytes cultured in agarose gel.
AB  - Adult articular chondrocytes are each surrounded by a heterogeneous
      microenvironment and together form the chondron. Since little is known of
      chondron development, agarose gel culture, confocal immunohistochemistry and
      image analysis have been used to characterize the molecular anatomy and temporal
      development of the chondrocyte pericellular microenvironment in vitro. Two
      structurally distinct domains were identified during the 12-week culture period.
      The first comprised a narrow glycocalyx, 1-3 microns in width, which consolidated
      over time and was rich in collagen types II, VI, IX and XI, fibronectin, decorin
      and the aggrecan epitopes, 5D4 and HABR. The second region emerged after 4-6
      weeks in culture and progressively developed a broad territorial region up to 12
      microns wide around the chondrocyte and pericellular glycocalyx. Co-localization
      studies confirmed the dominance of aggrecan epitopes 2B6, EFG-4, 5D4 and HABR in
      the territorial domain, whereas surface density mapping with NIH image revealed
      two patterns of staining, one punctate and stippled, the other more uniform in
      distribution. The pericellular differentiation identified appeared analogous to
      the chondrons of adult articular cartilage, and provides an appropriate in vitro
      model for further studies of cell surface receptor function in the orchestration
      of pericellular matrix assembly.

PMID- 9279555
TI  - Immunohistochemical localization of low-affinity nerve growth factor receptor in
      the enteric nervous system of adult rats.
AB  - The localization of low-affinity nerve growth factor receptor in the enteric
      nervous system of adult rats has been studied by immunohistochemistry using a
      monoclonal antibody (clone 192) against the rat receptor. Cryostat and whole
      mount sections were stained. By light and confocal microscopy, positive staining
      in neural structures was found in every part of the gut. In the ganglionic
      plexus, dense staining was detected in the neuropil surrounding neuronal cell
      bodies that were themselves devoid of immunoreactivity. Immunoelectron microscopy
      revealed deposition of reaction products on the outer plasma membranes of both
      perikarya and processes of neuronal as well as glial cells. Such a selective
      localization of the receptor in the plasma membrane, but not the cytoplasm,
      suggests that the mechanisms of receptor-ligand interaction in the gut may differ
      from those in the brain, where internalization of the receptor is observed in
      cholinergic cells. The present study provides the morphological basis for future
      studies designed to elucidate the functional significance of this enteric nervous
      system receptor. Since it is found in both neuronal and glial cells, it is
      probably under the influence of a number of trophic factors, including nerve
      growth factor.

PMID- 9279556
TI  - Neuropeptide-containing nerve fibres in the human parotid gland: a
      semiquantitative analysis using an antibody against protein gene product 9.5.
AB  - The occurrence and distribution of neuropeptide-containing fibres in the human
      parotid gland were examined by the peroxidase-antiperoxidase method with
      attention to the quality of fixation and the condition of patients. Many fibres
      immunoreactive for neuropeptide Y (NPY) and vasoactive intestinal polypeptide
      (VIP) and a moderate number of galanin-positive (GAL) fibres were distributed
      around the acini. A moderate number of NPY and VIP fibres were distributed around
      the intercalated ducts. The semiquantitative mean densities (+/- SD) of
      periacinar NPY, VIP and GAL fibres expressed as a percentage of the total protein
      gene product (PGP) 9.5 immunoreactive fibres were 75.62 +/- 7.25%, 70.52 +/-
      9.33% and 41.76 +/- 5.45%, respectively, whereas those of substance P (SP),
      calcitonin gene-related peptide (CGRP) and FMRF amide (FMRF) fibres were below
      10%. The mean densities of NPY and VIP fibres around the intercalated ducts
      expressed as the percentage of PGP 9.5 fibres associated with these ducts were
      52.37 +/- 6.19% and 59.62 +/- 7.02% respectively. Those of SP, CGRP, GAL, and
      FMRF fibres were below 10%. The densities of NPY, VIP, SP, CGRP, GAL and FMRF
      fibres around the striated and excretory ducts were also below 10%. In the
      vasculature, NPY fibres were the most prominent. Similarly, the mean density of
      perivascular NPY fibres was 93.76 +/- 2.03%. No somatostatin or leucine or
      methionine enkephalin immunoreactivity was detected around the acini, duct system
      or blood vessels. These findings suggest that, in this gland, the periacinar NPY,
      VIP and GAL fibres may participate in regulating the synthesis of saliva and its
      secretion and that perivascular peptidergic fibres, especially NPY fibres, may be
      involved in controlling local blood flow.

PMID- 9279557
TI  - Detection of human papillomavirus DNA in genital lesions by enzymatic in situ
      hybridization with Fast Red and laser scanning confocal microscopy.
AB  - Human papillomavirus (HPV) infection with potentially oncogenic types 16 or 18 is
      common in genital lesions especially in uterine carcinomas. In such lesions, in
      situ hybridization with non-radioactive probes is a powerful tool for the
      histopathologist to detect and type HPV DNA either on cell deposits or on tissue
      sections. The use of an immunohistochemical method involving alkaline phosphatase
      and Fast Red TR salt/naphthol AS-MX phosphate is proposed for use with
      conventional bright-field or fluorescence microscopy as well as by laser scanning
      confocal microscopy. The alkaline phosphatase-Fast Red reaction has the advantage
      of producing a red precipitate that permits the detection of in situ
      hybridization signals by bright-field microscopy, and of obtaining a strong red
      fluorescence characterized by a lack of bleaching when excited by a green light.
      Therefore, the alkaline phosphatase-Fast Red reaction is well adapted for
      observations by fluorescence and confocal microscopy, the latter method allowing
      the detection, in tissue sections of cervical intraepithelial lesions, of small
      punctate and large diffuse hybridization signals, considered as integrated and
      episomal states of HPV DNA respectively. The combination of in situ hybridization
      with the alkaline phosphatase-Fast Red reaction and confocal microscopy is
      particularly convincing when hybridization signals are of small size and/or of
      low fluorescence intensity, especially if they are present in various focal
      planes; in such conditions, infected cells are easily detected by three
      dimensional reconstruction. Therefore, this combination is a suitable method for
      identifying and characterizing HPV DNA in cells and tissue sections.

PMID- 9279558
TI  - Aberrant glycosylation based on the neo-expression of poly-N-acetyllactosamine
      structures in squamous cell carcinomas of the head and neck.
AB  - An immuno- and lectin-histochemical study was performed to investigate the
      aberrant expression of blood group-related antigens and poly-N-acetyllactosamine
      structures in squamous cell carcinomas of the maxillary sinus, the larynx, the
      apipharynx, the hypopharynx, the oral cavity, the parotid gland and the tonsil
      from 52 patients using monoclonal antibodies against A, B and H antigens, and six
      lectins, UEA-I, PNA, VVA-B4, PWM, LEA and DSA. In addition, GSA-II staining
      following endo-beta-galactosidase digestion procedure was also applied. A, B and
      H antigens were expressed in most normal epithelial cells of head and neck
      organs, and depended on the patient blood type. However, in squamous cell
      carcinoma, A antigen was not detected in eight out of 25 individuals of blood
      groups A and AB, although B antigen was consistently expressed in carcinoma cells
      from all the B and AB individuals. On the other hand, H antigen was expressed in
      carcinoma cells not only from all blood group O individuals, but from 32 out of
      35 individuals of blood groups A, B and AB. T and Tn antigens, which are
      recognized by PNA and VVA-B4, were strongly expressed in carcinoma cells from 40
      and 42 out of 52 individuals respectively. Reactivity with GSA-II staining
      following endo-beta-galactosidase digestion, which recognizes linear poly-N
      acetyllactosamine structures, was found in a few malignant cells from 21
      individuals. Staining with anti-A, -B and -H monoclonal antibodies and UEA-I
      lectin was diminished after endo-beta-galactosidase digestion in some cases.
      Lectins specific for poly-N-acetyllactosamine, such as PWM, LEA and DSA,
      exhibited reactivity in some malignant cells from 30, 22 and 32 out of 52
      individuals respectively. These results suggested that the expression of the
      blood group-related antigens is suppressed and immature carbohydrate chains, that
      is H, T and Tn antigens, are accumulated in squamous cell carcinomas of the head
      and neck. The results further suggested that poly-N-acetyllactosamine structures
      are simultaneously synthesized along with the deletion of A antigen and the
      accumulation of precursors.

PMID- 9279559
TI  - Differential expression of alpha 1(IV), alpha 2(IV), alpha 5(IV) and alpha 6(IV)
      collagen chains in the basement membrane of basal cell carcinoma.
AB  - Type IV collagen, the major component of basement membrane, consists primarily of
      alpha 1(IV) and alpha 2(IV) chains. Recently, other types of collagen IV chains,
      i.e. alpha 3(IV), alpha 4(IV), alpha 5(IV) and alpha 6(IV) chains, have been
      identified by protein chemistry and molecular cloning. We have examined the
      diversity of the assembly of alpha (IV) chains of the basement membrane
      surrounding tumour nests of basal cell carcinomas, in tissues from 11 patients,
      by immunohistochemical analysis using specific monoclonal antibodies to six alpha
      (IV) chain. The immunostaining profile of each chain differed with respect to the
      histological subtypes of basal cell carcinoma. In the morphea-like subtype, which
      was more invasive, alpha 1(IV) and alpha 2(IV) chains were discontinuously
      stained, and alpha 5(IV) and alpha 6(IV) chains were entirely absent. However, in
      the superficial subtype, which was non-aggressive, alpha 1(IV), alpha 2(IV),
      alpha 5(IV) and alpha 6(IV) chains were well stained compared with the other
      subtypes of basal cell carcinoma. In addition, in the solid subtype, which showed
      slow growth and ulceration, alpha 1(IV) and alpha 2(IV) chains were continuously
      stained, and alpha 5(IV) and alpha 6(IV) chains were discontinuous or absent. The
      assembly of alpha 5(IV) and alpha 6(IV) chains into the basement membrane was
      inhibited in the solid and morphea subtypes of BCC. This differential expression
      of type IV collagen chains seems to be associated with the invasive potential of
      basal cell carcinoma.

PMID- 9279561
TI  - Histological phenotypes of enteric smooth muscle disease causing functional
      intestinal obstruction in childhood.
AB  - AIMS: Functional intestinal obstruction or chronic idiopathic intestinal pseudo
      obstruction is due to defects either in the enteric innervation or in intestinal
      smooth muscle. We have studied full-thickness intestinal biopsies from 27
      patients with functional intestinal obstruction due to enteric smooth muscle
      disease by routine histology and electron microscopy together with histochemical
      and immunohistochemical techniques to detect changes in the intestinal smooth
      muscle. METHODS AND RESULTS: Two patients appeared to have an acquired intestinal
      myopathy as a result of an autoimmune process. In 25 the disorders were
      congenital, of these seven had segmental abnormalities limited to the rectum and
      distal colon and 18 had a diffuse disease affecting both the small and large
      bowel. We identified five apparent histological phenotypes of enteric muscle
      disease, three of which represent abnormalities in morphogenesis resulting in
      alterations in intestinal muscle layering and two exemplify intrinsic myocyte
      defects and/or changes in the extracellular matrix. CONCLUSIONS: Careful
      phenotyping of these patients is important in devising optimal treatment and in
      understanding the underlying defect as well as the possible genetic mechanisms
      resulting in these abnormalities. Recognition of autoimmune smooth muscle disease
      is helpful, since making the diagnosis influences the patient's management.

PMID- 9279560
TI  - The molecular histology of neoplasia: the role of the cadherin/catenin complex.

PMID- 9279562
TI  - Improved prognosis of solid-type poorly differentiated colorectal adenocarcinoma:
      a clinicopathological and immunohistochemical study.
AB  - AIMS: We rarely encounter solid-type poorly differentiated colorectal carcinoma,
      and their histogenesis and biological behaviour are not fully disclosed. METHODS
      AND RESULTS: A review of 60 poorly differentiated carcinomas of the colorectum
      was undertaken, 36 (59%) of which were located in the right side of the
      colorectum. Although, on the basis of the World Health Organization (WHO)
      classification solid carcinomas are included among undifferentiated carcinomas,
      the poorly differentiated carcinomas were divided into four types; 27 solid
      carcinomas (Sol.), 17 poorly differentiated adenocarcinomas (PDA), six signet
      ring cell carcinomas (Sig,) and 10 mucinous carcinomas (Muc.). Solid carcinomas
      revealed a solid alveolar growth of fairly uniformly sized tumour cells with
      occasional mitotic figures. This type of tumour had a relatively lower percentage
      of lymphatic permeation and lymph node metastasis compared with the other three
      types. The 5-year survival rates were 31% for all poorly differentiated
      carcinomas, 47% for the Sol. type, 32% for the PDA type, and 0% for both the Sig.
      and the Muc. types, with a rate of 72% for well-differentiated adenocarcinomas
      selected as controls. Immunohistochemically, bcl-2 protein expression was
      demonstrated in 38% of the Sol. type, but in only 12% of the other three non
      solid types, this difference being significant (P < 0.05). CONCLUSIONS: These
      findings suggest that solid carcinomas of the colorectum should be regarded as a
      distinct type of poorly differentiated carcinoma, leading to a good prognosis.

PMID- 9279563
TI  - Immunohistochemical assessment of proliferative activity in mammary
      adenomyoepithelioma.
AB  - AIMS: Two cases of adenomyoepithelioma of the breast were examined by
      immunohistochemistry to evaluate proliferative activity of epithelial and
      myoepithelial components. METHODS AND RESULTS: The tumours showed a bicellular
      pattern of gland-forming epithelial cells and proliferative myoepithelial cells
      with clear cytoplasm. They showed foci of monotonous growth of myoepithelial
      cells devoid of glands with low mitotic rate (1-2/10 high-power fields) and mild
      cytological atypia. Immunohistochemically, the glandular cells were positive for
      epithelial membrane antigen, cytokeratin (KL-1 and CAM5.2) and carcinoembryonic
      antigen, whereas tumour cells with clear cytoplasm were reactive with muscle
      specific actin (MSA), alpha smooth muscle actin, vimentin, and S100 protein but
      negative for desmin. Proliferative activities assessed by MIB-1 (Ki-67)/MSA
      positive cell index were greater in myoepithelial cells in both cases (19.2% and
      17.7%) as compared to those in epithelial cells (MIB-1/CAM5.2 index: 10.2% and
      9.5%). CONCLUSIONS: These results might account for the previous findings that
      myoepithelial components predominate over the epithelial ones in an advanced
      stage of this tumour as well as in recurrent or metastatic lesions.

PMID- 9279564
TI  - Anti-cytokeratin 5/6: a positive marker for epithelioid mesothelioma.
AB  - AIMS: Previous studies using frozen material have suggested that cytokeratin 5 is
      expressed by pleural mesothelioma but not by adenocarcinoma. In the present
      study, reactions for cytokeratins 5 and 6 were investigated in 33 pleural
      mesotheliomas and 27 secondary adenocarcinomas of the pleura using formalin
      fixed, paraffin-embedded material and a commercially available antibody (anti
      cytokeratin 5/6). METHODS AND RESULTS: All of the adenocarcinomas originated in
      the peripheral lung. The epithelioid component of the mesotheliomas gave a
      strongly positive reaction: the reaction in sarcomatoid or desmoplastic areas was
      absent or weak. Twenty-two of the adenocarcinomas were negative, in four there
      was a weak, equivocal reaction, and in one there was patchy positivity.
      CONCLUSIONS: We conclude that this antibody is potentially a useful positive
      marker for the identification of the epithelioid variant of mesothelioma in
      formalin-fixed and paraffin-embedded material.

PMID- 9279565
TI  - Expression and prognostic value of c-erbB-2 oncogene product in human
      phaeochromocytomas.
AB  - AIMS: Amplification of c-erbB-2 proto-oncogene has been reported in endocrine
      tumours, but the results were unclear and no predictive prognostic value has been
      established in the case of phaeochromocytoma. We investigated the
      immunohistochemical expression of c-erbB-2 oncogene in 34 cases of human
      phaeochromocytoma (27 sporadic, seven familial type MEN (multiple endocrine
      neoplasm)) in order to find out if it could be used to differentiate sporadic and
      familial forms and whether c-erbB-2 expression is related to tumour biological
      behaviour. METHODS AND RESULTS: All the cases showed diffuse, generally
      heterogeneous, intracytoplasmic granular c-erbB-2 staining. The percentage of
      tumour cells expressing c-erbB-2 was used as the comparative variable. The
      percentage of c-erbB-2 positive cells had a statistically significant (P < 0.001)
      relationship with tumour aggressiveness, as manifested by the presence of distant
      metastasis or association with other malignant neoplasms. We also found
      significantly higher levels (P = 0.007) of c-erbB-2 overexpression in MEN
      phaeochromocytoma than in sporadic cases. CONCLUSIONS: These results clarify the
      important role of c-erbB-2 proto-oncogene in the pathogenesis of human
      phaeochromocytoma and confirm the unfavourable prognostic significance of c-erbB
      2 expression.

PMID- 9279566
TI  - Matrix metalloproteinases and tissue inhibitors of metalloproteinases in thyroid
      C-cells and medullary thyroid carcinomas.
AB  - AIMS: Hyperplastic C-cells of the thyroid and medullary thyroid carcinomas (MTCs)
      were studied immunocytochemically for calcitonin, carcinoembryonic antigen (CEA),
      chromogranin A, matrix metalloproteinase (MMP)-2 and -9, and tissue inhibitor of
      metalloproteinase (TIMP)-1 and -2. METHODS AND RESULTS: Non-neoplastic C-cells
      were positive for all these substances whereas MTC tumour cells were relatively
      weaker stained, and thyroid follicular cells were negative for all the substances
      studied. We have recently reported that pancreatic islet cells and islet cell
      tumours were positive for MMPs and TIMPs, and, in addition, anterior pituitary
      cells and pituitary adenomas and parathyroid gland and its adenomas were also
      positively stained. The MMP- and TIMP-positive endocrine cells correspond to
      Pearse's APUD cells, derived from neural crest and endodermal cells. CONCLUSIONS:
      MMPs and TIMPs may well be added as newly recognized markers for neuroendocrine
      cells. The possible function of MMP-TIMP homeostasis in C-cells and MTCs is
      discussed.

PMID- 9279568
TI  - Angiotropic lymphoma with endocrine involvement.
AB  - AIMS: Two cases of angiotropic high-grade B-cell lymphoma are described in which
      involvement of endocrine glands was a prominent feature. METHODS AND RESULTS: One
      patient had marked unilateral adrenomegally due to lymphoma within adrenal blood
      vessels. He is alive 5 years after presentation following combination
      chemotherapy. The diagnosis was made at autopsy in the second patient who
      presented with pyrexia of unknown origin and had hypothyroidism and a thyroid
      nodule. The thyroid gland and pituitary showed striking involvement by
      angiotropic lymphoma and the thyroid nodule was a cavernous haemangioma heavily
      colonized by lymphoma cells. CONCLUSIONS: Our cases illustrate endocrine organ
      manifestations of this rare disease. The condition may respond to combination
      chemotherapy.

PMID- 9279567
TI  - Islet cell tumour with vacuolated lipid-rich cytoplasm: a new histological
      variant of islet cell tumour.
AB  - AIMS: A previously unreported clear cell variant of islet cell tumour of the
      pancreas is described. METHODS AND RESULTS: By light microscopy, the cytoplasm of
      the clear cells was finely reticulated and vacuolated. Immuno-histochemical and
      electron microscopy studies confirmed the endocrine nature of the tumour.
      CONCLUSIONS: The clear cell morphology was due to the accumulation of lipid in
      the cytoplasm.

PMID- 9279569
TI  - Primary spinal paragangliomas: a clinicopathological and immunohistochemical
      study of 30 cases.
AB  - AIMS: Extra-adrenal paragliomas are neoplasms which have been the subject of much
      debate regarding parameters to establish their biological behaviour. This study
      describes the clinicopathological and immunohistochemical features of 30 cases of
      spinal paragliomas. METHODS AND RESULTS: There were 15 male and 15 female
      patients. The median age at diagnosis was 46 years (range 20-74 years). Fourteen
      patients presented with back pain, two with numbness of the lower extremities,
      one with difficulty in walking and one with spinal cord compression. Nineteen
      tumours were located in the lumbar region, six in the cauda equina, two in the
      filum terminale, two in the thoracic region and one in the cervical region. All
      patients underwent gross total excision. The size of the tumours ranged from 10
      to 50 mm. Histologically, 18 neoplasms showed alveolar (Zellballen) pattern,
      seven a spindle component, two eosinophilic granular cells suggestive of
      oncocytic metaplasia, two melanin pigment and one ganglion cells. Positive
      immunohistochemical results include: neuron-specific enolase 23/23 (100%),
      synaptophysin 21/23 (91%), S100 protein 22/23 (95%, sustentacular cells), leu
      enkephalin 11/23 (47%), somatostatin 8/23 (34%), focal glial fibrillary acidic
      protein 7/23 (30%), focal keratin 5/23 (21%), neurofilament proteins 3/23 (13%)
      and adrenocorticotrophic hormine (ACTH) 1/23 (4%). Follow-up information obtained
      in 20 patients show 17 patients alive over a period of 6-216 months. One patient
      had bone metastases. Two patients died of unrelated causes, including one of
      congestive heart failure and one of myocardial infarction. CONCLUSIONS: In our
      experience, spinal paragangliomas behave as slow-growing tumours susceptible to
      potential cure by total excision. We agree with the current World Health
      Organization (WHO) classification as grade I tumours. Less than 1% may be locally
      aggressive. Spinal paragangliomas immunoreact not only for conventional
      neuroendocrine markers but also for peptides including somatostatin and ACTH and
      focally for the epithelial marker keratin.

PMID- 9279571
TI  - Calcifying fibrous pseudotumour of visceral peritoneum.
AB  - AIMS: Calcifying fibrous pseudotumour, a recently characterized rare but
      distinctive lesion, has been reported previously only in soft tissues and in the
      pleura. We describe four cases of calcifying fibrous pseudotumour which arose in
      the visceral peritoneum of the small bowel and stomach. METHODS AND RESULTS: In
      contrast to the calcifying fibrous pseudotumour of soft tissues which generally
      occurs in children, all four cases in our report occurred in adults. We consider
      the calcifying fibrous pseudotumour to be a distinctive tissue reaction.
      CONCLUSIONS: Its characteristic appearance of concentric whorls of lamellated
      collagen associated with psammoma bodies and other forms of dystrophic
      calcification is entirely different from all other lesions displaying hyaline
      collagenous deposits, such as inflammatory pseudotumour, desmoid, hyalinizing
      granuloma or fibrous plaques of peritoneum.

PMID- 9279570
TI  - Sclerotic lipoma: lipomas simulating sclerotic fibroma.
AB  - AIMS: We report a series of five unusual subcutaneous lipomas characterized by
      prominent stromal sclerosis in a storiform arrangement. METHODS AND RESULTS: All
      lesions occurred in young male adults (23.0 +/- 9.5 years), three lesions were on
      the scalp and two on the hands. Clinically, lipoma, chondroma or some form of
      cyst were suspected. In contrast to sclerotic fibroma ('circumscribed storiform
      collagenoma') a variable number of adipocytes were interspersed within the
      fibrosclerotic background. These cells also showed immunoreactivity for S100
      protein as well as intracytoplasmic lipid deposits ultrastructurally. None of the
      lesions recurred within a follow-up period of between 0.5 and 9 years.
      CONCLUSIONS: Our series suggests that sclerotic lipomas should be classified with
      fibro- and myxolipomas, angiolipomas, spindle cell and pleomorphic lipomas, as an
      additional characteristic subtype of lipoma. Sclerotic lipomas are often
      misdiagnosed as a sclerotic fibroma, but are essentially fatty tumours and are,
      at least in our small series, not associated with Cowden's disease.

PMID- 9279572
TI  - High-grade papillary cystadenocarcinoma of the tongue.
AB  - AIMS: Salivary gland tumours of the tongue are rare. The most common type is low
      grade mucoepidermoid carcinoma followed by adenoid cystic carcinoma. Papillary
      cystadenocarcinoma of salivary glands are uncommon lesions with low-grade
      mucoepidermoid carcinoma followed by adenoid cystic carcinoma. Papillary
      cystadenocarcinoma of salivary glands are uncommon lesions with low-grade
      histological and clinical features. We report a high-grade papillary
      cystadenocarcinoma in an 80-year-old man who presented with a tongue mass and
      metastatic disease in the neck. METHODS AND RESULTS: He was treated with partial
      glossectomy and bilateral neck dissection but developed local and regional
      recurrences 6 months later. The tumour had a prominent cystic appearance and had
      areas of necrosis. The cyst lumen was occupied by numerous papillae lined by
      pseudostratified columnar cells with a high nuclear-cytoplasmic ratio. The
      cytoplasm was eosinophilic, the nuclei were pleomorphic and exhibited irregular
      nuclear membranes, vesicular chromatin and prominent eosinophilic nucleoli. The
      mitotic activity was high and there were occasional abnormal mitotic figures.
      Metastatic carcinoma was present in four lymph nodes. The differential diagnosis
      of this unusual lesion includes cystadenoma, salivary duct carcinoma and
      metastases. CONCLUSIONS: This case and a review of the literature indicates that
      papillary cystadenocarcinomas of salivary gland origin exhibit a wider
      morphologic spectrum than described in the latest World Health Organization (WHO)
      classification which defines these lesions as low-grade neoplasms.

PMID- 9279573
TI  - Angiosarcomas of the breast developing post radiotherapy.
AB  - AIMS: This paper describes two contrasting cases of post-radiotherapy
      angiosarcomas of the breast. They illustrate the spectrum of malignant vascular
      tumours that may occur in the breast. These tumours are extremely rare and
      knowledge of their natural history is limited. The prognosis suggested by the few
      published cases of poorly or moderately differentiated angiosarcomas suggest a
      poor prognosis often with a fatal outcome. METHODS AND RESULTS: This was
      confirmed by our first case a poorly differentiated angiosarcoma, occurring 10
      years after radiotherapy for breast carcinoma with death occurring from
      metastatic angiosarcoma 6 months later. Our second, more recently diagnosed case,
      was a well-differentiated angiosarcoma, occurring 5 years post radiotherapy for
      breast cancer. She remains well 12 months after the diagnosis of sarcoma but her
      long-term outlook is more problematic to predict. Only five previous cases of
      well-differentiated post-radiotherapy angiosarcoma of the breast have been
      reported with limited follow-up (average 2 years). CONCLUSIONS: Communication
      with the authors of four of the papers since their publication has provided
      valuable additional information and indicates a potentially good outlook for this
      woman in the longer term. A second cellular component was also found in these
      malignant vascular tumours. These spindle cells distinct from the malignant
      endothelial cells have not to our knowledge been described previously and their
      possible nature is discussed.

PMID- 9279574
TI  - Diagnostic criteria for pseudomalignant osteoblastoma.
AB  - AIMS: Osteoblastoma is a rare bone tumour and differentiation from osteosarcoma
      is occasionally a diagnostic problem. The difficulty is further compounded when
      such a lesion microscopically shows cytological or architectural atypia. METHODS
      AND RESULTS: A case of pseudomalignant osteoblastoma occurring in the left iliac
      crest of a 34-year-old Chinese woman is presented. Radiographic findings were non
      diagnostic, but favoured a benign yet locally aggressive lesion. Histologically
      the diagnosis was based on the findings of classical osteoblastoma areas
      harbouring pseudomalignant osteoblasts in the absence of mitoses, but there were
      co-existing atypical architectural features also. CONCLUSION: The significance
      and pathogenesis of the 'permeative pattern' are discussed. Difficulties in
      differentiating borderline lesions are emphasized.

PMID- 9279576
TI  - Primary amyloidosis complicated by systemic necrotizing arteritis.

PMID- 9279575
TI  - Amyloid colitis mimicking collagenous colitis.

PMID- 9279577
TI  - Development of effective living vaccines against bovine babesiosis--the longest
      field trial?
AB  - Between 1959 and 1996, research was performed to change a vaccine against
      babesiosis in Australia and to improve it as actual or threatened untoward field
      responses became apparent. The most significant change occurred in 1964 with the
      traditionally used carriers of Babesia being replaced as vaccine donors by
      acutely infected splenectomised calves. This ensured the infectivity of the
      vaccine and was fortuitously associated with a reduction in the virulence of
      Babesia bovis in vaccine. Since then, more than 27 million doses of highly
      infective vaccine have been supplied from the laboratory at Wacol near Brisbane.
      This vaccine reduced serious losses from babesiosis in vaccinated cattle in
      Australia to very low levels and has now gained acceptance worldwide. Research to
      ensure the continuing effectiveness of the vaccine has proved to be essential.

PMID- 9279578
TI  - Population genetic structure of Ixodes ricinus in Switzerland from allozymic
      data: no evidence of divergence between nearby sites.
AB  - Ixodes ricinus is a vector and reservoir of numerous infectious agents,
      especially Borrelia burgdorferi, the agent of Lyme disease. In Switzerland, its
      ecology and physiology have been well studied. Moreover, the foci of some
      infectious agents transmitted by this tick are identified. They can display
      relatively to extremely small geographical size depending on the diseases
      considered. In order to understand how the gene flows occur and to characterise
      the genetic structure of Ixodes ricinus populations, we used an indirect method
      based on genetic markers: allozymes. The sampling was carried out in 5
      localities. Eighteen loci were analysed and 2 appeared polymorphic. This shows
      the low allozymic variability displayed by Ixodes ricinus. Based on these 2 loci,
      the populations appeared panmictic in Switzerland. This may be explained by the
      wide range of vertebrate species this tick can infest, especially birds. However,
      the result is surprising if we consider the extreme localisation of the foci of
      some infectious agents. We conclude that more powerful genetic markers could be
      used in order to better understand the epidemiology of tick-borne diseases in
      Switzerland.

PMID- 9279579
TI  - Zoonotic potential of infection with Fasciola spp. by consumption of freshly
      prepared raw liver containing immature flukes.
AB  - Mice were successfully infected with metacercariae of the Japanese Fasciola sp.,
      resulting in the recovery of a mean number of 110 live immature flukes per mouse
      4-5 days after inoculation. Twenty-four mice were then inoculated orally, each
      with a mean number of 68 freshly recovered immature flukes. The livers of 7 of
      the 24 recipient mice showed migratory lesions of capsular and subcapsular
      granulomatous infiltration and 2 of those mice also had haemorrhagic lesions. The
      lesions were typical of those caused by active migration of early immature
      flukes. However, no flukes were found in the livers of the recipient mice at
      necropsy when the flukes were aged 14 weeks. In another experiment, 10 piglets
      were given fresh livers of mice harbouring approximately 2000 live immature
      flukes aged 3-7 days. Two additional piglets were inoculated with 2000
      metacercariae of Fasciola. All pigs were killed when the flukes were 14 days old.
      Granulomatous lesions were present in all pigs, except in those that were given
      livers containing flukes aged 7 days. The lesions were localized, forming well
      defined foci, different from the typical migratory lesions normally observed in
      mouse or sheep liver at the early stage of fluke migration. From the 10 pigs
      given livers, 65 live flukes were recovered at necropsy, 0.29% of the estimated
      number of immature flukes given. From the 2 pigs which received 2000
      metacercariae each, a total of 198 flukes were recovered (5%). The results of the
      experiments suggest that humans consuming raw liver dishes prepared from fresh
      livers infected with immature Fasciola spp. could become infected with liver
      fluke.

PMID- 9279580
TI  - Albendazole versus ricobendazole (albendazole-sulphoxide) against enteral and
      parenteral stages of Trichinella spiralis in mice.
AB  - Comparison of the anthelmintic activity and pharmacokinetic profiles following
      albendazole (ABZ) and albendazole-sulphoxide (ricobendazole = RBZ) administration
      was made in a mouse model for helminthic infections. Swiss CD-1 mice were
      experimentally infected with Trichinella spiralis and treated with either ABZ or
      RBZ at 3 different stages of the parasite life-cycle: pre-adult (day 1 p.i.),
      migrating larvae (days 13, 14 and 15 p.i.) and encysted muscle larvae (days 34,
      35 and 36 p.i.). Plasma concentrations of albendazole-sulphoxide (ABZSO) were
      measured in age matched non-infected mice by high performance liquid
      chromatography (HPLC), after administration of ABZ or RBZ dosed at 50 mg ABZ
      equivalent kg-1. ABZSO pharmacokinetic profiles following ABZ or RBZ
      administration were similar, although the Tmax (1.83 +/- 0.30 and 0.41 +/- 0.28,
      respectively) were significantly different (P < 0.01). Against pre-adult stages
      ABZ was significantly (P < 0.05) more effective than RBZ when administered at 10
      mg kg-1 (96.5% and 78.0% reduction with respect to the control group). Migrating
      and encysted larvae were less sensitive to both compounds and dose rates had to
      be increased to 100 mg kg-1 to achieve significant efficacies. Against parenteral
      stages, ABZ was significantly more effective than RBZ when both were given at 100
      mg kg-1 (64.0% and 44.2% reduction against migrating larvae and 94.7% and 65.5%
      reduction against encysted larvae, respectively). In conclusion, RBZ was not more
      effective than ABZ against enteral and parenteral stages of Trichinella spiralis.

PMID- 9279581
TI  - Nucleic acid stains as indicators of Cryptosporidium parvum oocyst viability.
AB  - We developed nucleic acid dye staining methodology for untreated, heat-treated
      and chemically inactivated C. parvum oocysts. The nucleic acid staining was
      compared to in vitro excystation and animal infectivity using split samples of
      oocysts. Among the nucleic acid stains tested, SYTO-9, hexidium and SYTO-59
      stained the oocysts consistently, and the staining was related to the infectivity
      of the oocysts to neonatal CD-1 mice but not to in vitro excystation. The nucleic
      acid viability assay was used to determine log-inactivations of the oocysts after
      treatment with ozone, chlorine, chlorine dioxide and combinations of different
      chemical disinfectants, and was found to indicate log-inactivation levels similar
      to that of animal infectivity. A combined immunofluorescence-nucleic acid
      staining assay was developed for the oocysts of C. parvum and this assay will be
      invaluable for the detection and viability of oocysts in the laboratory and in
      environmental samples.

PMID- 9279582
TI  - Pattern of Cryptosporidium parvum oocyst excretion by experimentally infected
      dogs.
AB  - Six 6-week-old Beagle dogs were fed Cryptosporidium parvum oocysts of calf
      origin. All 6 dogs shed oocysts in faeces. Greater numbers of oocysts were
      detected with a Weber concentration technique (formalin-ethyl acetate extraction
      and NaCl centrifugal flotation) stained with either fluorescent antibody or
      modified Ziehl-Neelsen than with other formalin-ether or -ethyl acetate
      extraction methods. Oocyst numbers g-1 of faeces rose from days 3 to 5 to a first
      and highest peak lasting to days 7-9, and 5 of the 6 dogs passed oocysts for at
      least 80 days. However, the numbers of oocysts detected in the dogs' faeces were
      low, only 16.1% of the samples in the first month after infection and 2.5%
      thereafter contained > or = 10000 oocysts g-1 of faeces. Oocyst production was
      cyclical, with 19.3% of samples negative in the first month after infection and
      42.5% thereafter.

PMID- 9279583
TI  - Kinetics of specific immunoglobulin A, M and G production in the duodenal and
      caecal mucosa of chickens infected with Eimeria acervulina or Eimeria tenella.
AB  - The development and appearance of antibody was studied in the intestine and serum
      from histocompatible GB1 chickens orally infected with oocysts of Eimeria
      acervulina (restricted to the duodenum) or Eimeria tenella (restricted to the
      caeca). The local immune response was measured as the specific antibody levels in
      the supernatants of intestinal fragments (duodenum and caecum) maintained in
      culture for 16 h at 41 degrees C, 5% CO2, 95% air. Specific IgM was detected 1
      week after E. acervulina infection, and the specific IgA and IgG contents of the
      duodenum and caecum were significantly elevated (P < 0.001) after 2 weeks. The
      intestinal specific IgG content was raised. E. tenella infection resulted in
      specific IgA only in the parasitized area during the second week post-infection
      (P < 0.05). Specific IgM and IgG were both detected in the duodenum and caecum,
      respectively, 1 and 2 weeks p.i. Production of parasite-specific immunoglobulins
      was always significantly higher in the parasitized than in the unparasitized
      areas (caeca for E. acervulina, duodenum for E. tenella). This ex vivo culture
      assay of intestinal fragments used to measure the mucosal immune response of
      intestinal areas showed a significant production of specific IgA and IgM. In
      addition, high levels of IgG were also measured. The role of this specific IgG in
      Eimeria infection remains to be determined.

PMID- 9279584
TI  - A novel cDNA clone of Schistosoma japonicum encoding the 34,000 Dalton eggshell
      precursor protein.
AB  - A cDNA clone encoding the 34 kDa eggshell protein of Schistosoma japonicum was
      isolated from an adult female cDNA library with a rabbit antiserum raised against
      the 34 kDa female worm fraction. A 230 bp-insert of this clone (Sj23A) was
      introduced in frame into the expression plasmid vector, pMAL-c2, and the
      recombinant fusion protein of the Sj23A transiation product was induced in
      Escherichia coli. The antiserum raised against the recombinant protein reacted
      only with the native 34 kDa protein of mature female worms, which localized in
      the vitelline cells of the vitelline glands. By reverse transcription-polymerase
      chain reaction (RT-PCR) analysis, it was found that the gene corresponding to the
      Sj23A was expressed exclusively in mature female worms. The clone Sj23A showed a
      high degree of homology to the genes for the eggshell precursor proteins of
      Fasciola hepatica. At the deduced polypeptide level, the Sj23A also had
      similarities with the F. hepatica-protein sequence, the amino acid composition
      [high glycine (16%), lysine (12%) and tyrosine (11%)] and the presence of
      tyrosine residues flanked by glycine. The clone Sj23A also shared an extensive
      sequence homology with 3 S. mansoni expression sequence tags (ESTs). The present
      results suggest that the protein encoded by the female-specific Sj23A gene of S.
      japonicum is widely conserved in trematodes and plays a significant role as a
      precursor involved in eggshell formation.

PMID- 9279585
TI  - Pathogenicity of experimental caryosporosis.
AB  - Pathogenicity of the coccidia C. bigenetica and C. simplex was studied in
      experimentally inoculated pigs, goat kids (untreated and immunosuppressed) and
      severe combined immunodeficient (SCID) mice. The major pathological changes of
      caryosporosis were similar in all inoculated animals. In pigs and goat kids,
      caryosporosis was self-limiting, with clinical responses that included focal
      swelling and erythema of the muzzle, snout, jaws, cheeks, eyelids, bases of the
      ears, backs of the necks, scrotum, external genitalia of females, legs and
      footpads. Histopathological changes were characterized by involvement of the
      cutaneous mononuclear phagocyte system with an inflammatory exudate containing
      numerous macrophages, especially around the root sheaths, sensory nervous
      corpuscles of the hair follicles and surrounding dermal free nerve endings. The
      tactile hair follicles in the muzzle, snout and upper jaw were most severely
      changed. In SCID mice, inoculation with C. bigenetica or C. simplex caused a
      severe, fatal, systemic disease characterized by dissemination of numerous
      caryosporan developmental stages into the host mononuclear phagocyte system. This
      study presents evidence that both caryosporan species tested caused similar
      clinical signs and lesions of dermal coccidiosis in the mammalian secondary
      hosts.

PMID- 9279586
TI  - Effects of adult and larval Haemonchus contortus on abomasal secretion.
AB  - Abomasal pH and serum pepsinogen and gastrin were increased in parasite-naive
      sheep by infection with either larval or adult H. contortus. Four sheep received
      10000 larvae intraruminally and 9000 adult worms were given directly via an
      abomasal cannula to another 4 sheep. The latter animals were dosed orally with
      0.4 mg kg-1 ivermectin 4 days after worm transfer and their recovery was
      monitored for a further 8 days. Whereas the presence of adult worms rapidly
      induced changes in the secretory activity of the abomasum, the early larval
      stages had minimal effects up to the 4th day post-infection. After either larval
      or adult infection, the initial hypergastrinaemia began at the same time as the
      increase in abomasal pH, but serum gastrin continued to increase after abomasal
      pH had reached a maximum and returned more slowly to normal values after
      drenching. The increase in serum pepsinogen did not precede those in the other
      parameters, unlike the earlier hyperpepsinogenaemia which occurs with Ostertagia
      infection. Three of the 8 infected sheep had no detectable serum pepsinogen
      increase during the parasitism while showing typical effects on abomasal pH and
      serum gastrin. The rapidity of the responses to the transfer of adult worms and
      to their removal by treatment with anthelmintic supports a role for worm
      excretory/secretory (ES) products which possibly are not produced by the early
      larval stages. The similarity of responses to H. contortus and O. circumcincta
      infection suggests the involvement of the same or very similar ES products.

PMID- 9279587
TI  - False-positive Ascaris suum egg counts in pigs.
AB  - False-positive Ascaris suum egg counts in pig faeces are frequently observed
      under both experimental and natural conditions. Data from 12 experiments with A.
      suum infections in pigs were summarized and showed that the percentage of false
      positive faecal samples ranged from 4 to 36%. False-positive egg count values
      varied greatly between pigs and experiments (range 20-1060 eggs per gram faeces).
      Indoor experiments with pigs housed groupwise in pens generally produced more and
      higher false-positive egg counts, which may reflect differences in surface area
      and hence exposure to infective eggs, compared with pasture experiments. The
      positive predictive value (the number of pigs diagnosed positive by faecal sample
      that actually harboured worms) was low for indoor experiments (45%) compared with
      pasture experiments (89%). Differences in design for indoor experiments, such as
      floor type and use of bedding material, did not influence the positive predictive
      value (44-47%). A positive correlation was found (r = 0.56, P < 0.05) between
      faecal egg counts of true-positive and false-positive pigs that were penned
      together. The results of this survey strongly support previous suggestions that
      false-positive A. suum egg counts in pigs are the result of coprophagia in indoor
      experiments and coprophagia/geophagia in pasture experiments. False-positive A.
      suum egg counts in pig faeces may vary greatly in prevalence and magnitude, and
      depend in part on management/housing factors.

PMID- 9279588
TI  - Detecting genetic differences between groups of sheep during parasite infection.
AB  - When experiments are established to compare parasitological differences between
      genetic groups of animals, sampling of families within groups and individuals
      within families are both important. Many parasitological measurements are quite
      variable, so relatively large numbers of animals are required to detect small
      differences. Calculations are presented which show, for example, that 100 animals
      per genetic group will only have an 80% chance of detecting a difference in
      faecal worm egg counts as significant (P < 0.05) if the real difference between
      the groups is about 3-fold. When sampling genetic groups such as flocks or
      breeds, it is preferable to represent as many families as possible.

PMID- 9279589
TI  - Oral vaccination of mice with recombinant Schistosoma japonicum proteins induces
      specific anti-parasite antibodies and damage to adult worms after a challenge
      infection.
AB  - Mucosal immunisation by the oral route represents a cheap and simple method for
      delivering protective antigens to a host against gastrointestinal and respiratory
      pathogens. In the case of schistosome (bloodfluke) worms, 2 life-cycle stages may
      be exposed to the host's mucosa; the larval schistosomulum is exposed to the
      respiratory mucosa and, depending on the species, the egg may come into contact
      with the intestinal or urinogenital mucosa. Both IgA and some Isotypes of IgG
      have been implicated in protective immunity against schistosomiasis in humans and
      in experimental animal models. We have used a novel approach to determine whether
      schistosome-specific antibodies and protective immunity could be generated in
      mice by oral administration of bacterial lysates containing recombinant
      Schistosoma japonicum proteins. The mice produced specific antibodies to
      paramyosin and GST26, 2 important vaccine candidates for schistosomiasis, but
      there was no significant reduction in worm burdens in groups of mice immunised
      with either protein. Significantly, however, transmission electron microscopy
      revealed damage to the teguments of adult female and male S. japonicum worms
      obtained from mice vaccinated with recombinant paramyosin; there was also
      extensive damage to the tegument of male worms recovered from mice vaccinated
      with recombinant GST26. Our observations that oral vaccination with bacterial
      lysates containing recombinant proteins induced particular classes and subclasses
      of circulating antibodies with resultant damage to the surface of adult worms may
      have important implications for the future development of oral vaccines against a
      systemic infection such as schistosomiasis.

PMID- 9279590
TI  - Cytokine production during infection with Hymenolepis diminuta in BALB/c mice.
AB  - Levels of the cytokines IFN-gamma, IL-2, IL-3, IL-4 and IL-5 were monitored in
      cells from the mesenteric lymph nodes (MLN) of BALB/c mice infected with
      Hymenolepis diminuta after stimulation in vitro with Con-A. Infection was
      associated with an increased production of IL-3, IL-4 and IL-5 and a low
      production of IFN-gamma, indicating the preferential activation of a Th2
      response. It is suggested that this reflects the purely lumenal development of
      this worm. The results are discussed in relation to effector mechanisms known to
      be involved in immunity to intestinal helminths.

PMID- 9279591
TI  - Effect of IL-12 on granuloma formation induced by injected Schistosoma japonicum
      eggs.
AB  - The regulatory functions of IL-12 on granuloma formation by the eggs of S.
      japonicum in the lungs of BALB/c mice were studied. Mice were injected i.v. with
      the eggs to induce the pulmonary granuloma. On days 0, 1, 2, 3, 7, 8 after
      injection, mice were injected i.p. with murine rIL-12 at a dose of 1 microgram
      day-1 (Group I) or 3 micrograms day-1 (Group II) or with PBS as a control (Group
      III). On day 10, all mice were sacrificed. The areas of pulmonary granulomas in
      histological sections were quantitatively measured by image analyser and the
      levels of mRNA for IL-10, IFN-gamma, IL-12 and IL-5 were assayed by reverse
      transcriptase PCR (RT-PCR). The results showed that the mean area per granuloma
      was significantly decreased in Groups I and II as compared with Group III. As for
      cytokine induction, IL-10- and IFN-gamma-specific bands appeared in Groups I and
      II, but not in Group III. Bands for IL-5 appeared in all groups, while bands for
      IL-12 were not detected in any group. It is suggested that IL-12 could inhibit
      the Th2 dominant granuloma formation induced by the eggs of S. japonicum.

PMID- 9279592
TI  - Immunological interactions between Trichinella spiralis and Heligmosomoides
      polygyrus: cross reactivity between muscle larvae and antibodies raised to
      unrelated antigens.
AB  - It is documented that concurrent infections in mice with the 2 unrelated nematode
      parasites, Heligmosomoides polygyrus and Trichinella spiralis, can result in
      delayed rejection of the latter species. The basis of this immunological
      interference is not completely understood, but a possibility exists that
      antibodies induced by 1 species may interact with antigens produced by the other
      parasite. Therefore, it was investigated whether H. polygyrus infections may
      induce the production of antibodies which could cross react with T. spiralis
      muscle larval (m.l.) antigens. The results shown here indicate that this
      assumption is correct, and there is cross reactivity between antibodies produced
      against H. polygyrus, and T. spiralis m.l. antigens. Furthermore, antibodies
      which were not specific for either species were also able to bind to T. spiralis
      m.l. This is in agreement with recent evidence which has shown that antibodies
      that are not specific for H. polygyrus may still be absorbed by an H. polygyrus
      homogenate. It is considered that the binding of these antibodies may be involved
      in manipulation of the host immune response by T. spiralis.

PMID- 9279594
TI  - Aged citizens in the warning phase of disasters: re-examining the evidence.
AB  - While there is a strong consistent empirical literature on older citizens in the
      recovery period of disasters, there is much less research on how the elderly
      respond to disaster warnings. Furthermore, there are conflicting findings among
      these studies, some characterizing the elderly as noncompliant and less likely to
      cooperate with authorities, while others find the elderly no less responsive than
      other age groups. The current article reviews the literature in this area and
      tries to sort out conflicting findings in terms of the timing of the research and
      methodological considerations. Data are analyzed from nine disasters-representing
      flood events, volcanic eruptions, and hazardous materials emergencies-which show
      citizens over sixty-five years old no less likely to comply with disaster
      warnings.

PMID- 9279593
TI  - Wendell H. Krull (1897-1971).

PMID- 9279595
TI  - Self-concepts of low-income older women: not old or poor, but fortunate and
      blessed.
AB  - This article examines the extent to which low-income older women define
      themselves in stigmatizing terms, then explores the strategies they use to
      preserve a positive sense of self. Instead of considering themselves "old" or
      "poor," the sixty-two women interviewed defined themselves as "fortunate" and/or
      "blessed." The ability to see oneself as fortunate may be a significant component
      of successful aging.

PMID- 9279596
TI  - Attitude to aging among different groups in Nigeria.
AB  - Attitude to aging and the aged was surveyed in three groups of Nigerians, 1)
      caregivers living at home with the elderly, 2) various categories of hospital
      workers, and 3) the general public. Based on scores of an eleven-item
      questionnaire the best attitude was in caregivers, and the poorest in hospital
      workers. Years of education had an overall negative effect on attitudinal
      measurement. An inference from this study is that the elderly are still valued,
      but caregivers could be under some stress and would appreciate assistance. It is
      important for developing countries like Nigeria to begin to think seriously of
      what types of public assistance the elderly and their families would need.

PMID- 9279597
TI  - A study of aged population and associated health risks in rural India.
AB  - This article examines the prevalence of age-related diseases in different
      socioeconomic and demographic groups. The study is based on a sample of 267 aged
      persons (> 60 years) collected through a survey entitled "Aging and Health
      Conditions in Rural Area-A Sample Survey, 1990" conducted in the rural areas of
      the Varanasi district of Uttar Pradesh, a northern province of India. Various
      socio-behavioral factors are found to play a significant role in determining the
      health conditions of aged people. Also, illiteracy and poverty are found to have
      their own impact on health during aging. It is also noted that due to adverse
      familial relationships, many stress-related disorders occur which may result in
      the poor health of the elderly. Demands for old age pensions were made by most of
      the elderly people in the sample.

PMID- 9279599
TI  - Epidemiology--future directions.

PMID- 9279598
TI  - Olfactory acuity as a function of age and gender: a comparison of African and
      American samples.
AB  - A frequently reported finding in age-related sensory impairment is that olfaction
      shows consistent and uniform decline with age. In most studies, discerning
      whether loss in olfaction is due to aging per se or to factors extrinsic to the
      aging process (e.g., smoking, chemical exposure, head injury) is difficult.
      Moreover, studies of olfaction have generally relied on data collected from
      samples drawn primarily from Western societies. As such, little is known
      regarding differences in olfaction involving non-Western cultures. Using
      international data from the 1986 National Geographic Smell Survey, responses of
      19,219 American respondents and 3,204 respondents from Africa were analyzed. All
      respondents were screened for factors negatively affecting olfaction. Measures of
      olfactory acuity included odor detection, identification, intensity, and quality.
      The odor of interest was androstenone, a scent produced by bacteria on the human
      body and appearing in sweat. The results indicate that some measures of olfactory
      acuity tend to decline across age groups, but that this decline is less marked
      than reported in previous studies. The most important finding is that loss of
      olfaction is not consistent or uniform between geographic regions of America or
      Africa, between male vs. female respondents, or among the four measures of
      olfactory acuity. African respondents (both men and women) had significantly
      higher percentages of detection than did American respondents, women generally
      reported higher levels of olfactory functioning than did men, and some measures
      of olfaction were stable across age groups, or were higher among older
      respondents (e.g., odor identification).

PMID- 9279600
TI  - Genital herpes infection: a review.
AB  - Genital herpes infection is life-long and may result in painful and recurrent
      genital lesions, systemic complications, serious psychosocial morbidity, and rare
      but serious outcomes in neonates born to infected women, including permanent
      neurological handicap and death. Herpes simplex virus (HSV)-2 is the principal
      cause, with an increasing proportion of first-episode disease caused by HSV-1.
      Genital HSV transmission is usually due to asymptomatic viral shedding by people
      who are unaware that they are infected and clinical screening fails to detect
      most infections. Type-specific serological assays can distinguish the two viral
      subtypes, but these are expensive and currently restricted to a few research
      settings. Most infections are asymptomatic, or cause a mild illness which does
      not lead to health service attendance; but the limited evidence suggests a rise
      in disease incidence, perhaps related to a fall in HSV-1 age-specific
      prevalences. The prevalences of HSV genital infections increase with age and
      numbers of sexual partners, with higher rates in specific ethnic and low
      socioeconomic groups. However, infection is not restricted to high-risk
      populations. Antiviral agents, such as acyclovir, can reduce disease severity,
      prevent recurrences and shorten periods of viral shedding, but currently there
      are no effective population control measures. This may change with the advent of
      HSV vaccines, if their safety and long-term efficacy are confirmed. Possible
      applications for vaccines may include the suppression of disease and recurrences
      in patients with genital infections (immunotherapy), the prevention of viral
      transmission to their seronegative partners, and immunoprevention through
      vaccinating the latter. Economic evaluations of existing and potential control
      strategies, age-specific population HSV-1 and 2 seroprevalence studies for
      targeting future interventions, and cohort studies to elucidate the natural
      history of HSV-2 infections are needed.

PMID- 9279602
TI  - Histological diagnosis of precancerous lesions of the stomach: a reliability
      study.
AB  - BACKGROUND: Within the framework of a chemoprevention trial on stomach cancer,
      two substudies based on repeat measurement were undertaken to evaluate
      reliability of histological diagnoses of gastric precancerous lesions. METHODS: A
      subgroup of 45 subjects received two endoscopies separated by a period of one
      month. The two biopsies were reviewed by a single pathologist. A second subsample
      of 50 subjects had a single endoscopy and the biopsy results were reviewed by two
      pathologists. Agreement between the two diagnoses was assessed by Cohen's Kappa
      and by repeat frequency. RESULTS: When the same samples were reviewed by the
      pathologists involved in the trial, agreement was very high for advanced lesions
      (repeat frequency = 0.96 for intestinal metaplasia and 1.00 for dysplasia) but
      lower for less advanced lesions (repeat frequency = 0.73 for superficial
      gastritis and chronic gastritis, 0.65 for atrophic gastritis). When the same
      pathologist reviewed two sets of biopsies taken less than 2 months apart, the
      combination of random observer error and biopsy sampling error gave rise to quite
      low agreement, especially for early lesions, mainly attributable to biopsy
      sampling error. Comparison of diagnoses made at routine reading and at review by
      the same pathologist and by different pathologists showed substantial overall
      agreement with the exception of one pathologist for whom agreement was moderate.
      CONCLUSIONS: These results confirm that misclassification of histological
      diagnosis may be a relevant problem in chemoprevention trials of stomach cancer,
      more so when baseline diagnosis is taken into account in the analysis to estimate
      progression and regression rates of precancerous lesions. Further, the results
      suggest that misclassification is limited to early lesions, while diagnostic
      reliability of severe lesions is quite high.

PMID- 9279601
TI  - Surgical procedures associated with risk of ovarian cancer.
AB  - BACKGROUND: This historical cohort study was conducted to examine the
      relationship between gynaecological surgery and ovarian cancer risk. METHODS:
      Women were included if they had had tubal ligation, hysterectomy, or unilateral
      ovariectomy in Ontario between March 1979 and April 1993. The cohort was linked
      to the Ontario Cancer Registry and the Ontario mortality file. Person-years in
      the cohort were accumulated until death, the removal of both ovaries, a diagnosis
      of ovarian cancer, or the end of the study period 31 December 1993. Observed
      cancers were compared to expected based on Ontario age- and calendar period
      specific incidence rates. RESULTS: For tubal ligation and hysterectomy, fewer
      ovarian cancers were observed than were expected by age, calendar year of
      procedure, and length of follow-up; the observed/expected ratios were generally
      statistically significant. In contrast, no protective effect was evident for
      unilateral ovariectomy; in fact statistically significant excess cancers were
      seen in early follow-up periods. Observed/expected ratios were nearly identical
      and somewhat protective for the two strata defined by whether or not the ovaries
      were visualized. Disruption of the ovarian pathway conferred a protective effect,
      while no disruption significantly increased risk. CONCLUSIONS: The data do not
      support screening bias although short-term follow-up data indicate the
      possibility of detection bias. The long-term follow-up data, as well as the data
      on pathway disruption, are consistent with the hypothesis that the surgical
      procedures themselves may produce a protective effect against ovarian cancer,
      through alteration of the hormonal environment and/or by physical destruction of
      a carcinogen's route to the ovary.

PMID- 9279603
TI  - Validity of cerebrovascular disease mortality statistics in Bulgaria.
AB  - BACKGROUND: Cerebrovascular disease (CVD) is the leading cause of death in
      Bulgaria but the increasing mortality could be explained by inaccuracy of the
      statistical data and so investigation of the validity of CVD mortality statistics
      is of primary importance. METHODS: The investigation comprised three phases. An
      adequate questionnaire, requiring a reliable decision on the presence/absence of
      CVD in deceased patients was developed. During the first phase the questionnaire
      was validated on the basis of 325 inpatients aged 20 years and over. In the
      second phase the applicability of the questionnaire was proved and verified in
      patients who died outside hospital. This was performed by using 'twin'-copies of
      each questionnaire, completed in the first phase. In the third phase the
      applicability of the questionnaire for evaluation of CVD mortality statistics was
      checked using a sample of 119 death certificates. Statistical analysis of the
      information from each of the three phases was intended to evaluate the
      sensitivity and specificity of the questionnaire and to assess the validity of
      mortality statistics. RESULTS: High sensitivity of the questionnaire was
      established and it remained at the same value during each of the three phases of
      the study. Specificity was considered lower when the questionnaire was applied
      for those who died outside hospital and when used by non-neurologists. An
      underestimation of CVD by 8.9% was obtained in the first phase and it amounted to
      37.81% in the third phase. A high proportion of incomplete or unsystematically
      completed death certificates was found. This represents a potential source of
      inaccuracy in mortality statistics. CONCLUSION: The questionnaire developed for
      presence/absence of CVD in decreased patients proved to be a reliable instrument
      for certifying CVD mortality.

PMID- 9279604
TI  - Chlamydia pneumoniae and acute myocardial infarction in Jerusalem.
AB  - BACKGROUND: A number of studies in European and North American populations have
      reported associations between Chlamydia pneumoniae seropositivity and coronary
      heart disease (CHD). Our objective was to assess the association of IgG and IgA
      antibodies to C. pneumoniae with acute myocardial infarction (MI) in a population
      based case-control study in a Middle Eastern country. METHODS: Eligible cases
      aged 25-64 with a first acute MI were ascertained through an active surveillance
      system in Jerusalem hospitals between 1987 and 1989 (85% response). Controls were
      Jerusalem residents aged 25-64 sampled from the national population registry (83%
      response). Data on sociodemographic variables, CHD history and risk factors were
      collected by interview. Chlamydia serology, available for 93% of eligible
      participants, was performed by microimmunofluorescence on frozen stored samples
      using the TWAR antigen. Altogether, 251 male and 51 female cases, and 324 male
      and 162 female controls were analysed. RESULTS: Overall, high IgG titres (> or =
      128) were not associated with increased risk of acute MI (Odds ratio [OR] = 0.74
      for men [95% confidence interval (CI): 0.47-1.17] and 0.91 for women [95% CI:
      0.43-1.94]); neither were high IgA titres (> or = 80) (OR = 1.11 for men [95% CI:
      0.71-1.73] and 1.15 for women [95% CI: 0.33-4.0]). At IgG and IgA titres of > 32
      and > 20 respectively there was also no relation. CONCLUSIONS: An association of
      C. pneumoniae seropositivity with acute MI was not confirmed in this population
      with a very high IgG seropositivity prevalence of 84% in males and 69% in
      females. However, we cannot exclude the possibility that a postulated recent
      outbreak obscured an association with chronic C. pneumoniae infection.

PMID- 9279605
TI  - Association of leisure time physical activity with the risk of coronary heart
      disease, hypertension and diabetes in middle-aged men and women.
AB  - BACKGROUND: The association of physical activity and the risk of coronary heart
      disease (CHD), hypertension and diabetes has previously been studied mostly in
      separate follow-up studies. The present analysis focuses on the association
      between physical activity and these three metabolic diseases in a representative
      adult cohort. METHODS: The effect of the total amount and intensity of leisure
      time physical activity on the risk of the three diseases was studied in a cohort
      of 1340 men and 1500 women aged 35-63 years. RESULTS: During the 10 years of
      follow-up the incidence rates per 1000 person-years for CHD, hypertension and
      diabetes were 108, 142 and 64 for men and 75, 117 and 54 for women, respectively.
      In the Cox proportional hazards model the men's total amount of activity was
      inversely associated with the risk of CHD and hypertension. An age- and smoking
      adjusted relative risk of 1.98 (95% confidence interval [CI]: 1.22-3.23) for CHD
      and age-adjusted risk of 1.73 (95% CI: 1.13-2.65) for hypertension were found for
      the lowest third total activity group compared with the highest third of total
      activity. Vigorous activity once or more often a week was inversely associated
      with the risk of hypertension. For the women both a higher total amount of
      activity and weekly vigorous activity had an inverse association with the risk of
      diabetes. An age-adjusted relative risk of 2.64 (95% CI: 1.28-5.44) for diabetes
      was found for the lowest third activity group compared with the highest third.
      CONCLUSIONS: The results suggest a preventive effect of leisure time physical
      activity on CHD, hypertension and diabetes. This effect may differ among middle
      aged men and women and the relative importance of the total amount and the
      intensity may vary depending on the outcome measure.

PMID- 9279606
TI  - Short stature and heart disease: nature or nurture? The EARS Group.
AB  - BACKGROUND: Previous studies have demonstrated that short men are at increased
      risk of coronary heart disease (CHD). It has been suggested that the inverse
      relationship between adult height and CHD risk could be attributable to the fetal
      origins of CHD. METHOD: The hypothesis that transmissible factors could partly
      explain the association has been tested in the European Atherosclerosis Research
      Studies (I and II), in which a sample of healthy university students (cases),
      drawn from 18 European countries (male: n = 721; female: n = 330), whose fathers
      had had a documented myocardial infarction before the age of 55 years were
      compared to age- and sex-matched controls (male: n = 1056; female: n = 638).
      Information about lifestyle and birthweight was collected and a fasting blood
      sample was obtained from each subject. RESULTS: In females there was no
      difference in height between cases and controls but male cases were shorter than
      controls, on average by one cm, both in the EARS I (P = 0.02) and the EARS II
      studies (P = 0.01) and this difference was independent of reported birthweight
      and the fathers' educational attainment. In logistic regression the relationship
      was independent of the subjects' apolipoprotein B level, the other major
      biological discriminator of case-control status. CONCLUSION: In men at least,
      height appears to be an independent transmissible risk factor for CHD.

PMID- 9279608
TI  - Cluster versus individual randomization in adolescent tobacco and alcohol
      studies: illustrations for design decisions.
AB  - BACKGROUND: The decision to randomize by clusters of subjects such as a classroom
      or clinic versus individual randomization where some contamination may occur is
      examined within the framework of sample size issues. Estimates for background
      rates and intraclass correlations are also provided for adolescent tobacco and
      alcohol outcomes derived from a recent study using cluster randomization.
      METHODS: A ratio of adjusted sample sizes is derived which is a function of the
      intraclass correlation and cluster size for cluster randomization and total
      amount of contamination for individual randomization. Using estimated incidence
      rates and intraclass correlations, we provide a comparison of sample sizes for
      two plausible study outcomes. RESULTS: Small clusters such as a family or small
      classroom tend to have stronger within cluster dependence and cluster
      randomization would be clearly favoured over individual randomization. For
      moderately sized clusters, if contamination levels are likely to be high then
      cluster randomization would be a better choice. However in some situations where
      lower levels of contamination are expected, individual randomization may be
      preferred. With larger clusters, individual randomization should be considered
      when contamination rates are expected to be low. CONCLUSIONS: Investigators must
      carefully consider the choice of cluster randomization versus individual
      randomization in the context of likely contamination. In this paper we provided a
      basis for making this decision as well as examples to illustrate these decisions,
      and parameter estimates that will be especially useful for investigators in
      adolescent tobacco and alcohol studies.

PMID- 9279607
TI  - Black/white differences in leukocyte subpopulations in men.
AB  - BACKGROUND: Although counts of leukocytes differ substantially between blacks and
      whites, and are predictive of ischaemic heart disease (IHD), racial differences
      in counts of leukocyte subpopulations have received less attention. METHODS: We
      examined black/white differences in leukocyte subpopulations among 3467 white and
      493 black 31-45 year-old-men who had previously served in the US Army. Laboratory
      determinations were performed at a central location during 1985-1986. RESULTS:
      Black men had an 840 cell/microliter (or 15%) lower mean total leukocyte count
      than did white men, largely due to a 960 cell/microliter (or 25%) lower mean
      neutrophil count. Although black men also had a 20% lower mean monocyte count (=
      70 cells/microliter) than did white men, their mean lymphocyte count was 10%
      higher (approximately = 200 cells/microliter). Counts of various leukocyte
      subpopulations were associated with cigarette smoking, haemoglobin levels,
      platelet counts, and several other characteristics, but black/white differences
      in counts of neutrophils, lymphocytes, monocytes and other subpopulations could
      not be attributed to any of the examined covariates. CONCLUSIONS: Despite the
      relatively low counts of leukocytes and neutrophils among black men, their
      lymphocyte counts are generally higher than those among white men. It is possible
      that black/white differences in counts of various cell types may influence race
      specific rates of IHD, and future studies should attempt to assess the importance
      of leukocyte subpopulations in the development of clinical disease.

PMID- 9279609
TI  - Cause-specific mortality trends in The Netherlands, 1875-1992: a formal analysis
      of the epidemiologic transition.
AB  - BACKGROUND: The objective of this study is to produce a detailed yet robust
      description of the epidemiologic transition in The Netherlands. METHODS: National
      mortality data on sex, age, cause of death and calendar year (1875-1992) were
      extracted from official publications. For the entire period, 27 causes of death
      could be distinguished, while 65 causes (nested within the 27) could be studied
      from 1901 onwards. Cluster analysis was used to determine groups of causes of
      death with similar trend curves over a period of time with respect to age- and
      sex-standardized mortality rates. RESULTS: With respect to the 27 causes, three
      important clusters were found: (1) infectious diseases which declined rapidly in
      the late 19th century (e.g. typhoid fever), (2) infectious diseases which showed
      a less precipitous decline (e.g. respiratory tuberculosis), and (3) non
      infectious diseases which showed an increasing trend during most of the period
      1875-1992 (e.g. cancer). The 65 causes provided more detail. Seven important
      clusters were found: four consisted mainly of infectious diseases, including a
      new cluster that declined rapidly after the Second World War (WW2) (e.g. acute
      bronchitis/influenza) and a new cluster showing an increasing trend in the 1920s
      and 1930s before declining in the years thereafter (e.g. appendicitis). Three
      clusters mainly contained non-infectious diseases, including a new one that
      declined from 1900 onwards (e.g. cancer of the stomach) and a new one that
      increased until WW2 but declined thereafter (e.g. chronic rheumatic heart
      disease). CONCLUSIONS: The results suggest that the conventional interpretation
      of the epidemiologic transition, which assumes a uniform decline of infectious
      diseases and a uniform increase of non-infectious diseases, needs to be modified.

PMID- 9279610
TI  - Trends in occupational mortality among middle-aged men in Sweden 1961-1990.
AB  - BACKGROUND: Many European countries have in recent decades reported growing
      socioeconomic differentials in mortality. While these trends have usually
      paralleled high unemployment and increasing income disparities, Sweden had low
      unemployment and narrowing income differences. This study describes trends, 1961
      1990, in total and cardiovascular mortality among men, 45-69 years of age, in
      major occupational classes in Sweden. METHODS: From census data four cohorts were
      created from those enumerated in 1960, 1970, 1980 and 1985. Through record
      linkage with the Swedish cause of death registry the mortality in each cohort was
      followed for 5-10 years. Age-standardized mortality trends 1961-1990 were
      calculated for occupational groups, categorized according to sector of the
      economy. RESULTS: The increase in mortality among middle-aged men in Sweden 1965
      1980 was mainly a result of increasing cardiovascular mortality among industrial
      workers and farmers. In the 1980s the trend for these groups changed into a last
      decrease in mortality similar to that for non-manual occupations for the whole
      period. Consequently the rate ratio for industrial workers in comparison with men
      having a professional/managerial type of occupation increased from 0.98 to 1.43.
      The slowest decrease is now found among unqualified occupations in services and
      transportation. CONCLUSIONS: While Sweden, during the period studied, had
      narrowing income differentials and low unemployment this result points to the
      importance of working conditions in understanding trends and distribution of male
      adult mortality.

PMID- 9279611
TI  - Respiratory effects associated with indoor nitrogen dioxide exposure in children.
AB  - BACKGROUND: The human health effects of exposure to indoor nitrogen dioxide (NO2)
      are unclear, and few studies have examined the effects of short-term peak levels
      of exposure. METHODS: The association between indoor exposure to NO2 and
      respiratory illness was examined in 388 children aged 6-11 years. The NO2 levels
      were monitored during winter in 41 classrooms, from four schools with unflued gas
      heating and four schools with electric heating. Each classroom was monitored
      daily with 6-hour passive diffusion badge monitors over nine alternate weeks, and
      with hourly monitors over two of those weeks. Children living in homes with
      unflued gas appliances were also monitored daily over four evenings during times
      of gas use. RESULTS: Exposure to NO2 at hourly peak levels of the order of > or =
      80 ppb, compared with background levels of 20 ppb, was associated with a
      significant increase in sore throat, colds and absences from school. An increase
      in cough with phlegm was marginally significant. Significant dose-response
      relationships were demonstrated for these four measures with increasing levels of
      NO2 exposure. CONCLUSIONS: Short-term peak levels of exposure are important to
      consider in relation to adverse respiratory effects associated with NO2 exposure.

PMID- 9279612
TI  - Hospitalization of aboriginal and non-aboriginal patients for respiratory tract
      diseases in Western Australia, 1988-1993.
AB  - BACKGROUND: Aboriginal people have lower health standards than other Australians.
      Respiratory tract diseases are prominent causes of high morbidity and mortality
      rates in the Aboriginal population. However, very little is known about the
      patterns of respiratory illnesses which affect these people. METHOD: This paper
      compares Aboriginal and non-Aboriginal age-specific hospitalization patterns for
      respiratory tract diseases from 1988 to 1993 in Western Australia (WA). RESULTS:
      Aboriginal people were admitted for respiratory diseases 2-16 times more
      frequently than non-Aboriginals of the same age with considerable discrepancies
      in hospitalization rates particularly in infants, young children and older
      adults. High admission rates for acute respiratory tract infections, pneumonia
      and asthma occurred in Aboriginal infants. Pneumonia was a disproportionately
      frequent cause of admissions in Aboriginal infants, children and adults.
      Pneumonia is a more frequent cause of admission among non-metropolitan compared
      to metropolitan Aboriginals. Asthma was a frequent cause of admissions of
      Aboriginal children and hospitalization rates for this disease were higher in non
      metropolitan than metropolitan areas. Chronic obstructive airway disease and
      respiratory tract carcinoma were important uses of hospitalization in older
      Aboriginals. CONCLUSIONS: Admission rates for respiratory conditions were
      consistently higher among the Aboriginal population and in non-metropolitan
      areas. The overwhelming importance of infections among Aboriginal admissions has
      significant implications for the prevention and management of respiratory
      diseases among Aboriginal people.

PMID- 9279613
TI  - Deaths and injuries due to the earthquake in Armenia: a cohort approach.
AB  - BACKGROUND: This is the first population-based study of earthquake injuries and
      deaths that uses a cohort approach to identify factors of high risk. As part of a
      special project that collected data about the population in the aftermath of the
      earthquake that hit Northern Armenia on 7 December 1988, employees of the
      Ministry of Health working in the earthquake zone on 7 December 1988, and their
      families, were studied as a cohort to assess the short and long term impact of
      the disaster. The current analysis assesses short term outcomes of injuries and
      deaths as a direct result of the earthquake. METHODS: From an unduplicated list
      of 9017 employees, it was possible to contact and interview 7016 employees or
      their families over a period extending from April 1990 to December 1992. The
      current analysis presents the determinants of 831 deaths and 1454 injuries that
      resulted directly from the earthquake in our study population of 32,743 people
      (employees and their families). RESULTS: Geographical location, being inside a
      building during the earthquake, height of the building, and location within the
      upper floors of the building were risk factors for injury and death in the
      univariate analyses. However, multivariate analyses, using different models,
      revealed that being in the Spitak region (odds ratio [OR] = 80.9, 95% confidence
      interval [CI]: 55.5-118.1) and in the city of Gumri (OR = 30.7, 95% CI: 21.4
      44.2) and inside a building at the moment of the earthquake (OR = 10.1, 95% CI:
      6.5-15.9) were the strongest predictors for death. Although of smaller magnitude,
      the same factors had significant OR for injuries. Building height was more
      important as a factor in predicting death than the location of the individual on
      various floors of the building except for being on the ground floor of the
      building which was protective. CONCLUSIONS: Considering that most of the high
      rise buildings destroyed in this earthquake were built using standard techniques,
      the most effective preventive effort for this disaster would have been
      appropriate structural approaches prior to the earthquake.

PMID- 9279614
TI  - Risk of death from motor-vehicle injury in Brazilian steelworkers: a nested case
      control study.
AB  - OBJECTIVES: In a cohort of 21,816 Brazilian steelworkers we found mortality from
      motor-vehicle injury was twice that in the State population. A nested case
      control study was therefore undertaken to investigate possible socio-demographic,
      medical and occupational risk factors for this increased risk. METHODS: Cases
      were defined as all steelworkers in the cohort who died of motor-vehicle injury
      during employment in the period 1977-1992. For each case, four controls were
      selected at random from workers in the cohort who were employed at the time of
      death of the case, and who were born in the same year as the case. Data on socio
      demographic factors, and medical and occupational histories were obtained from
      personnel, industrial hygiene and medical records, and the relation of these
      factors to risk of motor-vehicle injury was analysed using conditional logistic
      regression. RESULTS: In a multivariate analysis, the risk of death from motor
      vehicle injury was independently associated with being unmarried (odds ratio [OR]
      compared to married = 3.21, 95% confidence interval [CI]: 1.84-5.59), having a
      hearing defect (OR = 2.28, 95% CI: 1.10-4.74) and exposure to moderate (OR =
      1.71, 95% CI: 1.03-2.83) or high (OR = 2.00, 95% CI: 1.18-3.39) levels of noise
      at work. The risk of fatal motor-vehicle injury increased with intensity of
      occupational noise exposure (P = 0.004). CONCLUSIONS: The raised risk of motor
      vehicle injury death associated with single marital status is likely to relate to
      selective factors in the types of individual who remain single, and behaviours
      associated with being unmarried. The raised risks in relation to hearing defects
      and exposure to occupational noise, factors that do not appear to have been
      examined previously, imply that occupational noise exposures might be a cause of
      fatal motor-vehicle accidents outside the workplace. This finding may have
      widespread public health consequences since high levels of noise in the workplace
      and occupationally acquired hearing deficits are prevalent in several
      occupations. Further investigation is needed to confirm the associated and its
      mechanisms and, if it is causal, to develop preventive strategies.

PMID- 9279616
TI  - Incidence and prevalence of primary biliary cirrhosis in the city of Newcastle
      upon Tyne, England.
AB  - OBJECTIVE: To describe the incidence and prevalence of primary biliary cirrhosis
      in an urban population between 1987 and 1994, using stringent inclusion criteria
      and a well-defined study area and population. DESIGN: Descriptive study based on
      a case register compiled by a retrospective and prospective case-finding exercise
      and examination of case notes. SETTING: The city of Newcastle upon Tyne. MAIN
      INCLUSION CRITERIA: (1) Definite cases: fulfilling all three of the following
      diagnostic criteria: positive antimitochondrial antibody (AMA) > or = 1:40;
      cholestatic liver function tests (LFT); diagnostic or compatible liver histology.
      (2) Probable cases: fulfilling two of these criteria. SUBJECTS: All cases of
      primary biliary cirrhosis identified by multiple case-finding methods, alive from
      1 January 1987 to 31 December 1994, in the defined area. MAIN OUTCOME
      MEASUREMENTS: Incidence and point prevalence rates by age and sex. RESULTS: In
      all, 202 potential cases were identified, of whom 160 met at least two inclusion
      criteria. In definite cases annual incidence varied from 14 to 32 (mean 22) per
      million whole population (with no clear trend) and point prevalence rose from 180
      per million in 1987 to 240 in 1994. Mean age at diagnosis in cases incident
      during the study period was 63.2 years (S.D. 11.1 years, range 39.8-85.7 years).
      CONCLUSIONS: Primary biliary cirrhosis is much more common in Newcastle than has
      previously been reported anywhere in the world, and prevalence appears to be
      rising.

PMID- 9279615
TI  - Ten-year survival of Down syndrome births.
AB  - OBJECTIVE: To determine the survival status of children with Down syndrome (DS),
      and to document factors influencing survival. DESIGN: Follow-up study of cases
      identified from the Dublin European Register of Congenital Anomalies and Twins
      (EUROCAT) Register. Follow-up was attempted for each case until death or 1992 or
      until the date last known to be alive. SETTING: Eastern Health Board, Dublin.
      SUBJECTS: In all, 389 DS children, born between 1 January 1980 and 31 December
      1989 were followed up. RESULTS: Survival rates of 88% at one year and 82% at 10
      years were found. There was a non-significant improvement in survival between the
      cohort born in 1980-1984 and that born in 1985-1989. Congenital heart defects
      reduced survival to 72% and complete atrio-ventricular canal defects (CAVD) had
      the poorest prognosis (58% survival at 10 years). Cases with CAVD showed a trend
      towards improved survival when surgically treated. Maternal age mother's county
      of residence, sex of infant, season of birth and presence of additional non
      cardiac congenital anomalies had no impact on survival. CONCLUSIONS: Four out of
      five DS children now survive at least 10 years. Adequate educational and health
      service provision needs to be made for them, especially those with congenital
      heart defects. The need for studies which compare survival and quality of life in
      DS children with CAVD who undergo cardiac surgery versus those who do not, taking
      account of various selection factors, is identified.

PMID- 9279617
TI  - Association between central nervous system infections during childhood and adult
      onset schizophrenia and other psychoses: a 28-year follow-up.
AB  - BACKGROUND: Maternal exposure to influenza epidemics during pregnancy may
      increase the risk of schizophrenia in the offspring. We investigated the
      association between central nervous system (CNS) infections defined prospectively
      up to the age of 14, and later onset of schizophrenia and other psychoses in the
      1966 birth cohort in Northern Finland, which covers 96% of all births in the area
      during that year. METHODS: Data regarding CNS infections were collected 1966
      1980. Registered diagnoses of psychoses in 1982-1993 were validated on DSM-III-R
      criteria. RESULTS: Out of 11,017 subjects, 145 had suffered a CNS infection
      during childhood, 102 of them a viral infection, 76 had DSM-III-R schizophrenia
      and 53 some other psychosis. Four cases of schizophrenia had suffered viral CNS
      infection and two cases of other psychosis bacterial infection. When neurological
      abnormalities and father's social class were adjusted odds ratio (OR) of
      schizophrenia after viral CNS infection was 4.8 (95% confidence intervals [CI] :
      1.6-14.0); the other significant risk factors being intelligence quotient (IQ) <
      85, perinatal brain damage and male sex but not epilepsy. Similarly adjusted OR
      of other psychoses was 6.9 (95% CI: 1.4-32.8) after bacterial CNS infection; the
      other significant risk factors being IQ < 85 and severe hearing defect. Two of
      the live viral infections were caused by Coxsackie B5 during an epidemic in which
      16 neonates were infected together. CONCLUSIONS: Central nervous system
      infections during childhood clearly carried an increased risk of adult onset
      schizophrenia or other psychoses, viral infections being important for
      schizophrenia, particularly Coxsackie B5 during the newborn period.

PMID- 9279618
TI  - Participation bias in a sexuality survey: psychological and behavioural
      characteristics of responders and non-responders.
AB  - BACKGROUND: Few studies of sexual attitudes and behaviour have quantified the
      direction and magnitude of participation bias, primarily because information on
      non-responders is difficult to obtain in cross-sectional surveys. METHOD:
      Australian adult twins (n = 9112) aged 17-52 years enrolled in a national,
      longitudinal research register were asked to participate in a postal survey
      concerning their sexual behaviour and attitudes. Individual consent was
      determined by separate return of a consent form; 27% explicitly refused, 19%
      initially agreed to receive a questionnaire, but subsequently did not return
      consent forms and 52% explicitly consented. Participation data were matched to
      social, psychological and behavioural information in a longitudinal data set.
      RESULTS: People who explicitly consented had higher levels of education, attended
      church less often, had less conservative sexual attitudes and voting preferences,
      were more likely to smoke cigarettes and drank alcohol more often than people who
      explicitly refused. On standard personality scales, responders were more novelty
      seeking and reward-dependent and less harm-avoidant than refusers. Structured
      psychiatric telephone interview data from 3674 individuals showed that, compared
      to refusers, responders had higher lifetime prevalence of major depression,
      alcohol dependence and childhood conduct disorder and also reported an earlier
      age at first sexual intercourse and higher rates of sexual abuse. In general,
      those who had initially agreed to receive the sex questionnaire but were
      subsequently lost were more similar to consenters than to refusers. CONCLUSIONS:
      Effect sizes on most measures were small. The broad profile suggests that postal
      surveys of sexual attitudes and behaviour may overestimate sexual liberalism,
      activity and adversity, although this bias should not seriously compromise
      population estimates.

PMID- 9279619
TI  - Wherein lies the truth? Assessment of agreement between parent proxy and child
      respondents.
AB  - BACKGROUND: The epidemiological study of diseases of childhood presents a special
      situation in that the principal respondent is almost always a person other than
      the index. Use of proxy respondents in paediatric epidemiology has been little
      studied compared with the use of surrogate respondents for adults. METHODS:
      Agreement between responses from children and their parents to identical
      questions about the children was assessed in a case-control study of childhood
      melanoma in Queensland, Australia. Weighted kappa and log-linear modelling
      techniques were used to measure agreement for ordinal data. RESULTS: Highest
      agreement was found for reports of unchanging physical characteristics such as
      eye colour (kappa = 0.88), hair colour (kappa = 0.76), and for history of
      residing on a farm (kappa = 0.84). Moderate agreement was seen for density of
      facial freckling (kappa = 0.62), propensity to sunburn (kappa = 0.46) and tanning
      ability (kappa = 0.47). Variables with low levels of agreement between parent
      proxy and child respondents included density of freckling on the shoulders (kappa
      = 0.28) and degree of moliness of the skin at age 5 years (kappa = 0.24).
      Agreement did not vary according to age or sex of the children. Log-linear
      modelling was performed to determine the type and magnitude of components of
      agreement. CONCLUSIONS: Agreement between responses from children and parent
      proxies depends largely upon the type of information sought, rather than
      characteristics of the respondents.

PMID- 9279620
TI  - Socioeconomic differentials in misclassification of height, weight and body mass
      index based on questionnaire data.
AB  - BACKGROUND: The purpose of this study was to analyse misclassification of height,
      weight and body mass index (BMI), derived from mail questionnaires, and its
      dependency on socioeconomic factors. METHODS: A random sample of 4442 adults aged
      18-84 years, living in Stockholm county, Sweden, were in 1984-1985 asked about
      their height and weight. A few months later 3208 of these adults participated in
      a health examination that included measures of height and weight. In this study
      we have used occupational class as the socioeconomic indicator. We have used
      sensitivity as a measure of misclassification of height, weight and BMI. RESULTS:
      The difference in mean measured height between socioeconomic groups I and III was
      2.7 cm for men and 2.0 cm for women. The mean difference in measured height
      between socioeconomic groups I and III was higher for men than for women in all
      age groups. The mean difference between self-reported and measured height was 0.6
      cm for men and 0.79 cm for women. For weight, the corresponding difference was 
      0.74 kg for men and -1.64 kg for women. Women's BMI was more underestimated than
      men's (-0.85 for women, -0.40 for men). When using self-reported height and
      weight for calculating BMI, 81% of the men and 78% of the women were classified
      correctly, but only 61% of the obese men and 55% of the obese women were
      identified. The BMI was underestimated in all socioeconomic groups. Manual
      workers had a lower proportion of underweight, compared to professionals and
      intermediate non-manual workers, while the objective measure showed the inverse
      relationship. The prevalence of overweight and obesity in men was 42% higher in
      socioeconomic group III compared with group I with self-reported data compared
      with 28% when measured. Underestimation of BMI was highest among women, the
      obese, the elderly, and male non-manual workers and female manual workers.
      CONCLUSIONS: Our study shows that socioeconomic differences in height, when using
      self-reported information, involve an underestimation. This means that the height
      differences between socioeconomic groups in Sweden may actually be higher than
      that reported by individuals in surveys. The socioeconomic differences in
      underweight tend to be underestimated for men, as well as obesity for women, when
      using self-reported information. The socioeconomic differences in overweight and
      obesity are shown to be overestimated for men.

PMID- 9279621
TI  - Average age at first occurrence as an alternative occurrence parameter in
      epidemiology.
AB  - BACKGROUND: Current epidemiological methods focus mostly on incidence rates and
      their ratios as measures of occurrence and effect. Incidence rates and rate
      ratios can be hard to interpret when the outcome disease is common. METHODS: The
      possibilities of using an alternative measure, average age at first occurrence of
      the disease, are discussed. RESULTS: Methods for the analysis of average age at
      first occurrence are illustrated in a study of occupation and disability pension.
      We estimate that the average age at pension among crane drivers is only about 0.8
      that of maintenance workers, regardless of the method, although the confidence
      intervals depend on the method. CONCLUSIONS: Average age at first occurrence is
      easier to interpret than the incidence rate for a very common disease. Because
      estimates are not readily available in software packages, we encourage further
      development of packaged software for this measure.

PMID- 9279622
TI  - Premature mortality in Italy during the first decade of the AIDS epidemic: 1984
      1993.
AB  - BACKGROUND: AIDS has become a leading cause of premature mortality in many
      countries, owing to the decline in other major causes of premature death and the
      increase in AIDS itself. This study was carried out to determine the trends in
      premature mortality due to selected causes in Italy. METHODS: Data from the
      Italian Mortality Data Base, for the ten years from 1984 to 1993 (the first
      decade of the AIDS epidemic) were analysed. Premature mortality was measured in
      terms of years of potential life lost before the age of 70 years (YPLL),
      excluding infant mortality. Trends in premature mortality due to AIDS were
      compared with those of the principal causes of premature death: lung cancer,
      colon-rectum cancer, stomach cancer, leukaemia, female breast cancer, uterine
      cancer, myocardial infarction, stroke, liver diseases, suicide, road accidents
      and overdose. RESULTS: In this period there has been a marked increase in
      premature mortality from AIDS both among males aged 1-69 years (from a rate of
      YPLL of 0.01 per 1000 in 1984 to 3.71 in 1993) and females of the same age group
      (from 0 deaths in 1984 to a rate of YPLL of 1.02). Throughout the same period all
      the other causes of premature death have been declining, with the exception of
      suicide and overdose among males, and overdose and lung cancer among females. For
      people aged 25-44 years, AIDS has become the greatest cause of premature death.
      The increasing trend in premature mortality due to AIDS is most pronounced in the
      northern and central areas of Italy. CONCLUSIONS: AIDS is the leading cause of
      death among males aged 25-44 years in Italy and is having an important impact on
      premature mortality among females in the same age group.

PMID- 9279623
TI  - Epidemiology of Helicobacter pylori infection among 4742 randomly selected
      subjects from Northern Ireland.
AB  - BACKGROUND: Despite the widespread prevalence and serious clinical sequelae of
      infection with Helicobacter pylori, there have been few large population-based
      studies, using randomly selected subjects, examining the epidemiology of this
      infection. AIM: To examine the distribution and determinants of H. pylori
      infection in a developed country. SUBJECTS AND SETTING: Overall 4742 subjects,
      aged 12-64, from Northern Ireland were randomly selected. METHODS: Helicobacter
      pylori specific IgG antibodies were measured by enzyme linked immunosorbent
      assay, using an acid-glycine extract antigen, in stored serum from subjects who
      had participated in three linked population-based surveys of cardiovascular risk
      factors performed in 1986 and 1987. RESULTS: The overall prevalence of H. pylori
      infection was 50.5%. Prevalence increased with age from 23.4% in 12-14 year olds
      to 72.7% in 60-64 year olds: chi 2 for trend 518, P < 10(-4). In subjects aged >
      or = 25, infection was more common in males (60.9%) than females (55.2%): chi 2 =
      9.53, P < 0.01. This relation remained significant after adjusting for age, and
      measures of socioeconomic class: odds ratio (OR) for infection, male versus
      female was 1.19 (95% confidence interval [CI]: 1.02-1.40). Infection was
      associated with social class: the adjusted OR of infection in subjects from
      manual social classes relative to those from non-manual classes was 1.7 (95% CI:
      1.47-1.98). Infection was significantly more common in current smokers and ex
      smokers than in subjects who had never smoked: adjusted OR for infection, ex
      smokers versus never smoked was 1.22 (95% CI: 1.01-1.49); for smokers of > or =
      20/day versus never smoked OR = 1.33 (95% CI: 1.05-1.67). Infection was not
      associated with height in adult males but mean height in infected women was lower
      than in uninfected women after adjusting for age and socioeconomic status:
      difference in mean height (SE), -0.85 cm (0.32), P < 0.01. There was no
      demonstrable relationship between H. pylori infection and current alcohol intake.
      CONCLUSIONS: This study demonstrated a high prevalence of infection in a
      population from a developed country. Previously reported associations between H.
      pylori infection, age, sex, social class, and reduced height in females were
      confirmed and smoking was identified as a possible risk factor for H. pylori
      infection.

PMID- 9279624
TI  - A case-control study of the effectiveness of BCG vaccine for preventing leprosy
      in Yangon, Myanmar.
AB  - BACKGROUND: Five randomized trials, a follow-up study, and six case-control
      investigations of BCG vaccine's effectiveness (VE) for preventing leprosy have
      been conducted internationally, with widely varying estimates of VE. Because of
      the difficulty of generalizing from disparate results, local estimates of VE are
      needed for health planning purposes and are currently particularly relevant,
      given the World Health Organization's (WHO) goal to eliminate leprosy by the year
      2000. METHODS: We conducted a case-control study in Yangon, Myanmar. Residents of
      Yangon between the ages of 6 years and 24 years who were listed in the National
      Leprosy Registry as being on active treatment for leprosy between December 1992
      and April 1993 were eligible to participate in the study as cases. Control
      subjects were matched to the cases on age, sex, and neighbourhood. RESULTS: One
      or more doses of BCG were associated with a VE of 66%. The results show a
      significant trend of increasing VE with increasing number of BCG doses (one dose,
      VE = 55%; two doses, VE = 68%; three doses, VE = 87%). One dose of BCG vaccine
      appeared to provide protection substantially higher than that found in an earlier
      vaccine trial in Myanmar, but consistent with results from case-control studies
      in other countries. CONCLUSIONS: These data suggest that BCG reduces the risk of
      leprosy in Myanmar, and that BCG vaccination of infants, along with early case
      finding and treatment, should be considered an important part of the leprosy
      intervention strategy.

PMID- 9279626
TI  - Theoretical versus 'atheoretical' epidemiology.

PMID- 9279625
TI  - Protective effects of topical antimicrobials against neonatal tetanus.
AB  - BACKGROUND: Case-control studies previously conducted in Pakistan suggested that
      topical antimicrobials might provide protection against neonatal tetanus (NNT)
      when applied to the umbilical cord wound during the first several days of life.
      The present case-control study, the largest such study yet reported, was
      undertaken in Punjab Province, Pakistan and afforded further opportunities to
      evaluate such effects. METHODS: A population-based, matched, case-control study
      was undertaken to assess topical antimicrobials and other factors related to NNT
      risk in rural parts of Punjab Province. RESULTS: Continuous use of antimicrobial
      agents (antibiotics and antiseptics) at delivery and during the first few days
      after delivery was highly protective in univariate testing (matched odds ratio
      0.2 [95% confidence interval: 0.11-0.64], P = 0.003), and remained significantly
      protective when other delivery and cord care practices were controlled. In
      contrast, applying nothing to the wound was risky compared with antimicrobial
      exposures. Hand washing and delivery by a trained birth attendant appeared
      protective. Application of animal dung or ash to the umbilical wound was
      hazardous. Similarly, predelivery cutaneous or intravaginal exposure of mothers
      to ghee (clarified butter) and delivery on a surface prepared with dried cow dung
      were risky, with significant interaction noted between them. Mortality and NNT
      were far more likely among previous births to mothers of cases. CONCLUSIONS:
      Topical antimicrobials offer a new, effective and inexpensive means to prevent
      NNT, and could usefully complement maternal immunization with tetanus toxoid in
      controlling the disease. Special prevention efforts should be directed towards
      mothers of NNT cases.

PMID- 9279628
TI  - Reduction in hospital stay.

PMID- 9279627
TI  - Population-based studies of IBD incidence in Italy and capture-recapture methods.

PMID- 9279629
TI  - Frederich H Epstein and lifestyle.

PMID- 9279630
TI  - Isolated congenital internal auditory canal atresia with normal facial nerve
      function.
AB  - The internal auditory canal forms as a result of mesoderm enveloping the eighth
      cranial nerve in the developing embryo. The mesoderm eventually transforms into
      cartilage and ultimately ossifies around the nerve, forming the internal auditory
      canal. It is theorized that atresia or stenosis of the internal auditory canal
      results from altered cochleovestibular nerve development secondary to faulty
      chemotactic mechanisms or a lack of end organ targets. Unilateral internal
      auditory canal anomalies are frequently seen in conjunction with other inner ear
      anomalies and occasionally with middle or external ear anomalies. Infrequently,
      it will occur as either an isolated or bilateral finding, but rarely
      simultaneously. The few citations of isolated, unilateral or bilateral internal
      auditory canal anomalies that are reported in the literature are usually
      associated with other systemic developmental anomalies, such as, cardiac septal
      defects, polycystic kidney disease, skeletal deformities and duodenal atresia. We
      present a case report of a patient with bilateral, congenital, internal auditory
      canal atresia and cochleovestibular deficits but, normal facial nerve function. A
      review of the literature is discussed as well as diagnostic considerations and
      treatment options including audiologic and communication rehabilitation.

PMID- 9279631
TI  - Complications of frontal sinusitis in adolescents: case presentations and
      treatment options.
AB  - Frontal sinusitis in adolescents can be a serious condition because of the
      severity of potential complications and rapid progression of disease. These
      complications may arise as a result of extension of the infection intracranially,
      to the frontal bone, and to the orbit. Infection may spread hematogenously or by
      direct extension. A series of seven adolescent patients with complications of
      frontal sinusitis is presented. Surgical options are necessitated by the location
      and extent of infection and include trephination, frontal sinus obliteration, and
      craniotomy. Recent advances in endoscopic sinus surgery have provided surgeons
      another access to the frontal recess. However, a combined
      otolaryngological/neurosurgical approach is essential for patients with
      intracranial complications.

PMID- 9279632
TI  - Prevalence of otitis media with effusion amongst pre-school children in Malaysia.
AB  - A cross-sectional screening test was done to determine the prevalence of otitis
      media with effusion amongst, preschool children in two district in Malaysia,
      namely Kuala Lumpur an urban district and Kuala Selangor a rural district. It
      involved 1097 preschool children aged between 5 and 6 years old. Presence of
      otitis media effusion (OME) is based on abnormal otoscopic finding, Type B
      tympanogram and absence of ipsilateral acoustical reflex. The overall prevalence
      rate of OME was 13.8%. The prevalence in Kuala Lumpur was 17.9%, while in Kuala
      Selangor it was 9.48%. Bottle feeding during infancy and high socioeconomic
      status of the parents was statistically associated with higher incidence of OME.
      Other factors such as race, premature delivery, passive smoking, allergy, asthma
      and family size, had no influence on the prevalence of otitis media with
      effusion.

PMID- 9279633
TI  - The risk of postoperative haemorrhage in tonsillectomy as an outpatient procedure
      in children.
AB  - The safety of performing tonsillectomy as an outpatient procedure is still
      questionable. This study determined whether there was an increased risk of
      postoperative bleeding by performing tonsillectomy as an outpatient procedure. A
      six years' retrospective chart review was made of 363 children who underwent
      tonsillectomy. Out of 363 children, 43 had been selected as an inpatient group
      before the operation, 264 patients were discharged home 6 h after the operation
      and were the outpatient group, and 56 children had to be kept overnight because
      of complications that had occurred. We compared the haemorrhage rate in the
      outpatient and the inpatient groups. We found no increase in the postoperative
      haemorrhage rate in the outpatient group. No statistically significant
      correlations were found between the children's ages, indication for surgery, type
      of operation or intra-operative complications and the risk of postoperative
      haemorrhage. Only children who had haemorrhage in the recovery room were
      identified as a high risk subgroup for recurrent bleeding. On the basis of our
      findings we believe that tonsillectomy can be performed as an outpatient
      procedure regardless of age, indication for surgery, or type of procedure, as
      long as good recovery room supervision exists for 4 to 6 h.

PMID- 9279634
TI  - Observer agreement about laryngoscopic assessment of papilloma.
AB  - BACKGROUND: Observer bias may confound the assessment of therapies utilized for
      recurrent respiratory papilloma, a recidivistic fluctuating disease. Any
      convincing change in a patient's disease must exceed the imprecision of the
      measuring system. MATERIALS AND METHODS: Videotapes of ten children, who had
      airway endoscopy for care of laryngeal papilloma, were edited. The videotapes
      were independently reviewed by six otolaryngologists, of whom five repeated their
      assessments 5 to 20 weeks later. The 'reference standard' was the operating
      surgeon's categorization of his patient's videotape. Agreement was calculated by
      the kappa statistic, the observed proportions of positive and negative agreement,
      and the proportion categorized as exact opposites, for each of twelve anatomic
      sites. RESULTS: Moderate agreement was found for both (a) the operative findings
      versus the later-determined 'reference standard', and (b) the 'reference
      standard' versus categorizations by other otolaryngologists. Intra-observer
      agreements were better than inter-observer agreements. Agreement as to whether or
      not papilloma involved each of twelve sites was within about 20% for the five
      pediatric otolaryngologists vs the 'reference standard', and within about 10% for
      the same reviewer. CONCLUSION: Videotapes may add objectivity to the assessment
      of laryngeal papilloma. For changes to be considered significant, an observer
      should identify a 10% change in the number of sites involved, or a 30% change in
      the extent of overall airway obstruction. For different observers, changes would
      have to be even greater to be meaningful.

PMID- 9279635
TI  - Trace elements in children with chronic and recurrent tonsillitis.
AB  - Trace elements are indispensable for life and play a very important role in the
      essential functions. According to some reports in the literature lower trace
      element levels increase the susceptibility to recurrent infections. Since there
      are no reports available in the English literature about the effects of trace
      elements on recurrent and chronic tonsillitis, 37 children with recurrent and
      chronic tonsillitis were evaluated for Zn, Cu and Mg levels. Serum levels of Zn
      in 6 patients were slightly lower than the normal limit. All the other serum
      levels of Zn, Cu and Mg were within the normal range. On the other hand, the mean
      serum level of Zn in the 37 patients was significantly lower than in a control
      group of 28 age and sex matched children. In contrast, the mean serum levels of
      Cu and Mg in the patients were significantly higher than in the control group.
      Whether this alteration in the trace element status causes or fosters recurrent
      and chronic tonsillitis is not clear.

PMID- 9279636
TI  - Acute right heart failure due to adenotonsillar hypertrophy.
AB  - A case is presented in which a child with underlying chronic lung disease,
      developed cor pulmonale and severe pulmonary hypertension as a result of
      adenotonsillar hypertrophy. His cardiac function acutely decompensated with an
      upper respiratory infection which exacerbated his obstructive sleep symptoms. Pre
      and postoperative documentation of cardiopulmonary function was critical in the
      peri-operative management of this patient. His severe pulmonary hypertension was
      stabilized using a nasopharyngeal airway and medications pre-operatively, in
      order to minimize his risk of anesthesia. He continued to require careful
      monitoring and manipulation of his medications after adenotonsillectomy and
      bronchoscopy. Serial echocardiograms documented the effects of the various
      interventions implemented in this patient. Severe acute right heart failure is an
      unusual complication of obstructive sleep apnea. However, this may become more
      common as more children survive prematurity and its associated chronic lung
      disease. These children may have subclinical lung disease and/or chronic
      pulmonary hypertension even after they no longer require supplemental oxygen and
      bronchodilators. Because these children are often tenuous, with regard to their
      cardiopulmonary function, they may be at increased risk to develop significant
      complications related to obstructive sleep apnea. It is important that a
      physician familiar with the management of pulmonary hypertension be involved in
      the care of these patients.

PMID- 9279637
TI  - Persistent cerebrospinal fluid otorrhea: a case of Munchausen's syndrome by
      proxy.
AB  - A case is presented of a young child who initially presented with recurrent
      bacterial meningitis 1 year after significant head trauma and was found to have
      cerebrospinal fluid (CSF) leakage into the middle ear. Surgical procedures were
      devised to attempt to stop this abnormal flow, but inexplicably clear otorrhea
      biochemically identical to CSF persisted for weeks. The child's mother was
      apparently soaking the surgical dressings with CSF obtained through a lumbar
      drain and confessed to this activity after she was found to have tampered with an
      intravenous catheter. This activity resulted in a prolonged hospital stay and
      several presumably unnecessary procedures. Munchausen's syndrome, typified by
      intentional mimicry of symptoms of serious illness backed by plausible medical
      history, is well-described. Rarer is the syndrome by proxy, where parents and/or
      caregivers, by falsifying histories, fabricating laboratory evidence, or
      deliberately generating bodily lesions, cause unneeded diagnostic and therapeutic
      procedures to be performed on their young victims. This form of child abuse is
      hidden by the perpetrator's apparent concern and involvement in the care of the
      victim. The literature is reviewed, this form of abuse is discussed, and the role
      of communication of suspicion between the various health care workers is
      stressed. The medical and social settings in which this disorder is prevalent are
      covered. Early detection of this entity is essential in rescuing the victim from
      life-threatening abuse and in obtaining appropriate therapy for the abuser.

PMID- 9279638
TI  - Antrochoanal polyp--a rare paediatric emergency.
AB  - An antrochoanal polyp, a common clinical entity, with a rare presentation is
      being reported. A 12 year old boy was brought to Accident and Emergency
      department with an unusual sudden presentation of polypoidal mass filling the
      oral cavity up to his incisors as a result of which he could not swallow and
      speak. Prior to this episode he had no complaints of the disease. An emergency
      removal was planned and only during the operation could it be diagnosed as a
      antrochoanal polyp because of its pedicle in the lateral wall of the nose, which
      was confirmed by histopathological examination.

PMID- 9279639
TI  - Infantile subglottic hemangioma: a review and presentation of two cases of
      surgical excision.
AB  - Subglottic hemangioma in infants is a well-defined entity with which
      otolaryngologists should be familiar. Although benign lesions with a natural
      history of regression, they may demand the attention of an otolaryngologist to
      maintain a secure airway. Throughout the years, multiple treatment options have
      been proposed and utilized for subglottic hemangioma. As of yet, however, there
      is no consensus as to the best treatment. Surgical excision is one treatment
      option available to the otolaryngologist which has previously received less
      attention. We review treatment options and report two cases of surgical excision
      of infantile subglottic hemangioma. Both patients were extubated by postoperative
      day number three and have remained symptom free. We support surgical excision as
      a valuable treatment option.

PMID- 9279640
TI  - The aging upper and middle face: an overview for the aesthetic surgeon.

PMID- 9279641
TI  - Clinical anatomy of the upper face.

PMID- 9279642
TI  - Millisecond CO2 laser skin resurfacing.

PMID- 9279643
TI  - Cosmetic botulinum toxin injections.

PMID- 9279644
TI  - The chemical peel.

PMID- 9279645
TI  - Eyebrow ptosis.

PMID- 9279646
TI  - Upper-eyelid blepharoplasty.

PMID- 9279647
TI  - The aponeurotic approach for the correction of blepharoptosis.
AB  - Blepharoptosis results from underaction of the eyelid protractors relative to the
      eyelid retractors causing the eyelid to be lower than its normal anatomic
      position. The lowering of the upper eyelid obstructs the superior visual field.
      Patients suffering from ptosis complain of eyelid asymmetry, fatigue, and
      difficulty reading. Ptosis is classified into categories based on the underlying
      anatomic abnormality. The categories: myogenic, aponeurotic, neurogenic, and
      mechanical may be differentiated based upon the levator function and the clinical
      examination. The type of ptosis and the degree of levator function determine
      which surgical interventions may be considered in an individual patient. The
      aponeurotic approach to the correction of blepharoptosis provides versatility and
      may be used for all degrees of ptosis provided the levator function is adequate.
      The aponeurotic approach allows for concomitant correction of associated
      dermatochalasis and eyelid crease abnormalities. Eyelid height and contour may be
      adjusted intraoperatively to obtain the most consistently favorable post
      operative results. Early postoperative adjustment enables revision of the eyelid
      with minimal additional surgical trauma.

PMID- 9279648
TI  - Minimal ptosis management.

PMID- 9279649
TI  - Lower-eyelid blepharoplasty.
AB  - In summary, the concept of one operation for all patients who present for lower
      eyelid blepharoplasty should be abandoned. Surgical procedures should be tailored
      for each individual, depending on the sources of concern and the anatomical
      defects present. The vast majority of patients are served best by combining
      transconjunctival blepharoplasty with adjunctive procedures. Transcutaneous lower
      lid blepharoplasty has few indications. By combining and choosing the proper
      techniques, the aesthetics surgeon can achieve lower-eyelid rejuvenation while
      preserving function and minimizing complications.

PMID- 9279650
TI  - The suborbicularis oculi fat in aesthetic and reconstructive surgery.

PMID- 9279651
TI  - Asian blepharoplasty.
AB  - Asian blepharoplasty requires an intimate knowledge of the anatomical subtleties
      distinct to the Asian patient. With this knowledge and a thorough understanding
      of patients' expectations, the surgeon confidently can achieve predictable
      results and a preservation of Asian eyelid qualities in those patients who desire
      it.

PMID- 9279652
TI  - Management of complications of blepharoplasty.

PMID- 9279653
TI  - Articular cartilage chondrons: form, function and failure.
AB  - The chondrocyte and its pericellular microenvironment together represent the
      chondron, historically considered the primary structural, functional and
      metabolic unit of articular and other hyaline cartilages. This review summarises
      research over the last 10 years to establish the molecular anatomy, functional
      properties and metabolic contribution of the chondron in articular cartilage
      homeostasis, and its failure during the initiation and progression of
      degenerative osteoarthritis.

PMID- 9279654
TI  - Demonstration of the intralobular lymphatics in the guinea pig pancreas by an
      enzyme-histochemical method.
AB  - Intralobular lymphatics in the guinea pig pancreas were demonstrated enzyme
      histochemically showing the extent, distribution and fine structure by combined
      light and transmission electron microscopy. 5'-nucleotidase(5'-Nase)-positive
      lymphatic vessels were present throughout the pancreas. Intralobular lymphatics
      among the acini were comparatively rare and generally independent of the blood
      capillaries, pancreatic ducts and acini. These lymphatics revealed the usual
      structural features, such as typical intercellular junctions and very tenuous
      vascular walls without continuous basal laminae. Fine precipitates of the cerium
      based reaction product for 5'-Nase activity were found to be associated with cell
      membranes of the lymphatic endothelium and pinocytotic vesicles. Lymphatics were
      not closely related to the endocrine islets, although alkaline
      phosphatase(ALPase)-positive blood capillaries were well developed. Collecting
      lymphatic vessels with valves with weaker 5'-Nase activity were also detected in
      the interlobular connective tissue. ALPase activity, absent in the lymphatics,
      was positive in the blood capillaries, suggesting that it is also a useful way
      demonstrating, histochemically, the blood capillaries in the guinea pig pancreas.

PMID- 9279655
TI  - Angiogenesis at the site of neuroma formation in transected peripheral nerve.
AB  - Investiture of new microvessels within an injured peripheral nerve trunk may
      determine the success that the local environment has in promoting axonal
      sprouting and regeneration. We therefore examined microvessel investment of 24 h
      14 d proximal nerve stump preparations in rat sciatic nerves. The stumps, later
      destined to form neuromas, were created by sciatic nerve transection with
      resection of distal branches to prevent distal reinnervation. Microvessels were
      studied in the proximal stump in semithin whole mount sections of nerve and by
      analysis of India ink perfused microvessel profiles. Quantitative image analysis
      was made of the luminal profiles of vessels perfused with India ink from unfixed
      sections of the stumps, contralateral uninjured nerves and sham-exposed but
      uninjured nerves. Evidence of angiogenesis was observed in stumps 7 d after
      transection, indicated by a rise in the total numbers of perfused microvessels
      and in the numbers of 2-6 microns diameter perfused microvessels. There was a
      shift in the histogram of the percentage of perfused microvessels towards the 2-4
      microns range and a reduction in the mean microvessel luminal area in the stumps.
      By 14 d, new microvessels were larger, indicated by an increase in total luminal
      area. New microvessels were prominent in the epineurial connective tissue or
      between layers of perineurial cells of former fascicles. Microvessels probably
      share a battery of trophic signals with other proliferating cellular elements in
      the milieu of the injured peripheral nerve trunk.

PMID- 9279656
TI  - Suppressive effect of perinatal testes on the differentiation of fetal ovaries
      transplanted into adult males in the rat.
AB  - A 14 d ovarian primordium was transplanted with a fetal testis (13-18 d and 21 d
      of gestation) or a neonatal testis (15, 20, 30 and 45 d after birth) into the
      renal subcapsular position of an adult male rat. Two weeks after transplantation,
      transplants were examined as to the degree of ovarian and testicular
      differentiation. In the combination of a 14 d ovary and a 13 d testis, there were
      3 types of result: either the ovary or the testis alone developed or both gonads
      developed well. Ovaries transplanted in union with 15-18 d testes did not
      develop, although the testes developed normally. Some ovaries in union with 21 d
      testes developed normally. In combination with infantile testes, the incidence of
      developed ovaries increased as the age of testes advanced. These results suggest
      that the 13 d fetal testes begin to suppress the development of cotransplanted 14
      d ovaries, that 14-18 d fetal testes maintain such suppressive effects and that
      this effect gradually diminishes in infantile testes as they progress toward 45 d
      after birth.

PMID- 9279657
TI  - Distribution of matrix metalloproteinases and their inhibitor, TIMP-1, in
      developing human osteophytic bone.
AB  - Connective tissues synthesise and secrete a family of matrix metalloproteinases
      (MMPs) which are capable of degrading most components of the extracellular
      matrix. Animal studies suggest that the MMPs play a role in bone turnover. Using
      specific polyclonal antisera, immunohistochemistry was used to determine the
      patterns of synthesis and distribution of collagenase (MMP-1), stromelysin (MMP
      3), gelatinase A (MMP-2) and gelatinase B (MMP-9) and of the tissue inhibitor of
      metalloproteinases-1 (TIMP-1) within developing human osteophytic bone. The
      different MMPs and TIMP showed distinct patterns of localisation. Collagenase
      expression was seen at sites of vascular invasion, in osteoblasts synthesising
      new matrix and in some osteoclasts at sites of resorption. Chondrocytes
      demonstrated variable levels of collagenase and stromelysin expression throughout
      the proliferative and hypertrophic regions, stromelysin showing both cell
      associated and strong matrix staining. Intense gelatinase B expression was
      observed at sites of bone resorption in osteoclasts and mononuclear cells.
      Gelatinase A was only weakly expressed in the fibrocartilage adjacent to areas of
      endochondral ossification. There was widespread but variable expression of TIMP-1
      throughout the fibrous tissue, cartilage and bone. These results indicate that
      MMPs play a role in the development of human bone from cartilage and fibrous
      tissue and are likely to have multiple functions.

PMID- 9279658
TI  - Morphometric analysis of the postnatal mouse optic nerve following prenatal
      exposure to alcohol.
AB  - Pregnant female mice were divided on day 12 post coitum into a control and an
      experimental group. The experimental group was given a single intraperitoneal
      dose of 0.015 ml/g body weight of 25% solution of alcohol in distilled water
      while the control group was exposed to a similar weight related dose of normal
      saline. The optic nerves were isolated from the offspring of both control and
      experimental groups at wk 2, 3 and 5 (i.e. during the juvenile period of
      postnatal development) and analysed by light and electron microscopy. Although in
      both groups the optic nerve grew in size rapidly during the period studied, the
      rate of growth in the experimental groups lagged behind that of the controls. The
      difference was initially significant but tailed off, so that by wk 5 it was no
      longer significant. The time of initial onset and progression of myelinogenesis
      in the optic nerve of alcohol exposed mice also lagged behind that of controls.
      In both groups the size distribution of the myelinated nerve fibres in the optic
      nerve was unimodal with a positive skewing for all ages. The spectrum of size
      distribution of the nerve fibres was, however, broader in controls than in the
      corresponding experimental groups. With increasing age the proportion of small
      and medium size fibres was greater in the experimental group than in the
      controls, while for the large diameter fibres the reverse was observed. It is
      suggested that this study may shed light on the teratogenic effect of 'binge'
      drinking during pregnancy and that it is the critical period when exposure occurs
      that is more important than the duration of administration.

PMID- 9279660
TI  - An ultrastructural study of cartilage resorption at the site of initial
      endochondral bone formation in the fetal mouse mandibular condyle.
AB  - An ultrastructural study was undertaken on cartilage resorption at the site of
      initial endochondral bone formation in the mouse mandibular condyle on d 16 of
      pregnancy. After resorbing the bone collar, the osteoclasts extended their cell
      processes into the cartilage matrix and made contact with hypertrophic
      chondrocytes. By means of cell processes or vacuolar structures, these
      osteoclasts entrapped the calcified cartilage matrices, cell debris, and the
      degraded uncalcified cartilage matrices. In particular, since the calcified
      cartilage matrices were sometimes seen to be disrupted within the osteoclastic
      vacuolar structures, they were probably disposed of by the osteoclasts. Invading
      endothelial cells giving rise to capillaries also directly surrounded the
      degraded uncalcified cartilage matrices and small deposits of cell debris. In
      addition, hypertrophic chondrocytes that had attached to or were in the process
      of attaching to the invading osteoclasts often enclosed the small calcified
      cartilage matrices. Other cell types that have often been reported in other
      regions of cartilage resorption were not seen at the site of initial endochondral
      bone formation in this study. Our findings in relation to cartilage resorption
      may therefore represent unique features of the site of initial endochondral bone
      formation site. We consider that the manner of cartilage resorption is likely to
      vary by site, age, and species.

PMID- 9279659
TI  - Analysis of fused maxillary incisor dentition in p53-deficient exencephalic mice.
AB  - Out of a total of 21 exencephalic p53-deficient embryonic and newborn mice, 6
      (28.6%) possessed fused maxillary incisor teeth. On histological analysis of the
      5 examples seen on day 19.5 of gestation and newborn mice, 3 varieties were
      observed: an example of 'simple' fusion, 3 examples of simple fusion each of
      which contained a 'dens in dente' ('tooth within a tooth'), and a single example
      in which the fused teeth were associated with a median supernumerary incisor
      tooth which, while deeply indenting the labial surface of the fused teeth, was in
      all locations a completely separate unit. 3-D reconstructions of the fused teeth
      demonstrated that they were all of the fusio subtotalis variety. No gross
      abnormalities were observed in the other dentition in these mice. It is noted
      that in mice fused maxillary incisor teeth are relatively commonly associated
      with both hypervitaminosis A-induced and trypan blue-induced exencephaly. It is
      believed that the presence of dens in dente within fused maxillary incisor teeth
      has only once been reported in mice, and the association between fused maxillary
      incisor teeth and a median supernumerary incisor tooth has not previously been
      reported in this species.

PMID- 9279661
TI  - Morphological and histochemical changes in the epididymis of hamsters
      (Mesocricetus auratus) subjected to short photoperiod.
AB  - The morphological involution and histochemical changes of the Syrian hamster
      (Mesocricetus auratus) epididymis induced by a short light period were
      investigated. Under short-day conditions, the epididymis showed marked
      morphological changes including a decrease in luminal diameter, disappearance of
      spermatozoa, increase of interductal tissue, increase of intraepithelial
      lipofuscin deposits, the presence of phagolysosomes in the principal cells and
      macrophage-like cells, and a considerable modification of most clear cells. With
      lectin histochemistry changes were found in the glycoconjugates of principal
      cells of the regressed epididymis, either a decrease (PNA, WGA, HPA and DBA) or
      an increase (MAA) in the affinity of lectins to the Golgi area, or a decrease
      (HPA) or an increase (PNA) in lectin binding to stereocilia. Both morphological
      and histochemical results showed that, under this light condition, the cauda
      epididymidis presented the most prominent alterations, and that the epididymis
      showed increased absorptive activity and a decreased synthesis of glycoproteins.
      All these changes are probably due to the decrease in testosterone levels.

PMID- 9279662
TI  - Neuron volume in the ventral horn in Wobbler mouse motoneuron disease: a light
      microscope stereological study.
AB  - Previous pathological reports have indicated that swollen and vacuolated
      motoneuron cell bodies are the most predominant feature characterising Wobbler
      mouse motoneuron disease, but there has been little supportive evidence using
      area measurements. The present study focuses on the possible role of changes in
      neuronal nuclear and perikaryal volumes in the cervical spinal cord ventral horn,
      using new and traditional stereological probes which provide unbiased estimates
      of volume. Semithin sections from the ventral horn of Wobbler mice and age and
      sex-matched phenotypically normal littermates were examined at 2 ages (young and
      old). The young Wobbler group had significantly larger volume weighted mean
      perikaryal volumes compared with age-matched controls, reflecting the presence of
      large swollen cells characteristic of this group; this situation was reversed in
      the control group. Number-weighted perikaryal volume estimates in the old Wobbler
      group were smaller than in age-matched controls. The variation in perikaryal
      volume was greatest in the young Wobbler group in which the coefficient of
      variation was 127%. The mean number weighted and volume weighted mean nuclear
      volumes were significantly smaller in the old Wobbler group compared with age
      matched controls and young Wobbler groups. The application of new stereological
      probes has enabled us to document more precisely these changes in neuronal
      structure in the Wobbler mutant mouse.

PMID- 9279663
TI  - Hair follicles of young Wistar strain hairless rats: a histological study.
AB  - The histological changes in hair follicles in hairless rats derived from the
      Wistar strain (hW, hairless Wistar) were examined from birth to maturity and
      compared with those of age-matched normal Wistar rats. In the 1st hair cycle, the
      hair follicles of hW rats were shorter and less well developed than those of
      Wistar rats. In early anagen, eosinophilic bodies were observed in some hair
      follicles which showed immature histological features. By using Tdt-mediated dUTP
      nick end labelling (TUNEL) method and electron microscopic examination, these
      bodies were confirmed to be apoptotic bodies. These follicles seemed to disappear
      by abnormal regression. In late anagen phase, the follicles in which the
      apoptosis did not occur showed enlarged hair roots with hypertrophy of the inner
      root sheath. Subsequently, when the follicles in normal Wistar rats synchronously
      regressed in the catagen phase, most of the follicles in hW rats similarly
      entered the catagen phase, but a few follicles did not regress completely and
      showed aberrant hair root enlargement. Finally, both types of follicle in hW rats
      formed follicular cysts. These abnormalities in follicle development (abnormal
      follicular regression and follicular cyst formation) appear to be associated with
      the hairlessness in this rat strain.

PMID- 9279664
TI  - Stereological estimates of nuclear number in human ventricular cardiomyocytes
      before and after birth obtained using physical disectors.
AB  - Design-based stereology is employed to estimate total numbers of myocyte nuclei
      and mean myocyte volume per nucleus in ventricles of fetal and early postnatal
      human hearts. Organs were collected postmortem from subjects varying in age from
      16 gestational wk to 40 postnatal wk. Numbers of myocyte nuclei per unit volume
      of ventricle were estimated using physical disectors (parallel pairs of
      sections). Absolute numbers were calculated by multiplying nuclear packing
      densities by ventricular volumes estimated from ventricular mass and tissue
      density. Volumes per nucleus were obtained via estimates of the combined volumes
      of all myocytes (or of the myocardium as a whole) and the numbers of myocyte
      nuclei. The findings showed that numbers of myocyte nuclei increase linearly from
      16 wk towards term. They were also consistent with the notion that hyperplasia
      ceases abruptly at birth or soon afterwards. The net rate of production of
      myocyte nuclei was about 38 x 10(7)/wk (2.3 million nuclei/h). The total volume
      of myocytes continued to expand in the same way from 16 wk to at least 35 wk of
      gestation. Published studies on the incidence of binucleate myocytes during early
      postnatal growth of the ventricles of rats suggest that the volume of a myocyte
      doubles prior to nuclear division. Prenatal growth in the human heart is
      consistent with this mechanism. Myocardial hypertrophy after birth must occur by
      cellular hypertrophy without karyokinesis.

PMID- 9279666
TI  - Localised degeneration occurs in aged mouse olfactory epithelium.

PMID- 9279665
TI  - The study of early human embryos using interactive 3-dimensional computer
      reconstructions.
AB  - Tracings of serial histological sections from 4 human embryos at different
      Carnegie stages were used to create 3-dimensional (3D) computer models of the
      developing heart. The models were constructed using commercially available
      software developed for graphic design and the production of computer generated
      virtual reality environments. They are available as interactive objects which can
      be downloaded via the World Wide Web. This simple method of 3D reconstruction
      offers significant advantages for understanding important events in morphological
      sciences.

PMID- 9279667
TI  - Superficial brachial artery continuing as the common interosseous artery.

PMID- 9279668
TI  - The significance of inflammatory reactions following cataract extraction and
      intraocular lens implantation.

PMID- 9279670
TI  - Postoperative inflammatory response to phacoemulsification and extracapsular
      cataract surgery: aqueous flare and cells.
AB  - PURPOSE: To compare the postoperative blood-aqueous barrier (BAB) breakdown
      induced by phacoemulsification with continuous curvilinear capsulorhexis (CCC)
      and by extracapsular cataract extraction (ECCE) with a linear capsulotomy.
      SETTING: Cataract and Refractive Surgery Research Unit, Department of
      Ophthalmology, St. Thomas' Hospital, London, United Kingdom. METHODS: Anterior
      chamber flare and cells were measured preoperatively and 1 day, 1 week, and 1 and
      3 months postoperatively in two parallel groups of 31 consecutive cataractous
      eyes. In Group 1, one surgeon performed ECCE with a linear capsulotomy; in Group
      2, a second surgeon performed divide and conquer phacoemulsification with CCC.
      The preoperative, intraoperative, and postoperative medication regimen was the
      same in both groups. RESULTS: Group 2 eyes had significantly lower anterior
      chamber flare and cell measurements in the first postoperative month than Group 1
      eyes (.01 < P < .00001). CONCLUSIONS: Phacoemulsification with CCC induced a less
      severe BAB breakdown than ECCE with a linear capsulotomy. Phacoemulsification
      with CCC may be preferable in high-risk eyes such as those with glaucoma,
      diabetes, or uveitis, which are prone to complications resulting from
      postoperative BAB breakdown.

PMID- 9279669
TI  - Correlation between intraocular lens hydrophilicity and anterior capsule
      opacification and aqueous flare.
AB  - PURPOSE: To study the correlation between a basic parameter of intraocular lens
      biocompatibility, hydrophilicity, and two clinical parameters, postoperative
      inflammation and anterior capsule opacification. SETTING: Miyake Eye Hospital,
      Nagoya, Japan. METHODS: Three combinations of IOLs that were identical in shape
      but had distinct contact angles of water were used in this prospective double
      masked study: (1) experimental comparison of collagen type IV and poly(methyl
      methacrylate) (PMMA) IOLs in rabbit eyes; (2) clinical comparison of heparin
      surface-modified and PMMA IOLs; (3) clinical comparison of three foldable IOLs,
      silicone, acrylic, and memory. One of the two IOLs being compared in each
      situation was randomly assigned to both eyes of each animal or patient. At 1 and
      3 months postoperatively, the degree of anterior capsule opacification and the
      amount of flare in the anterior chamber were determined. RESULTS: In all three
      comparative situations, greater postoperative inflammation and more rapid
      anterior capsule opacification was seen in the eyes with hydrophobic IOLs.
      CONCLUSION: There was a correlation between the hydrophilicity of an IOL and the
      severity of postoperative inflammation and the speed of anterior capsule
      opacification.

PMID- 9279671
TI  - Laser flare-cell measurement of inflammation after uneventful extracapsular
      cataract extraction and intraocular lens implantation.
AB  - PURPOSE: To prospectively evaluate the inflammation response after uneventful
      extracapsular cataract extraction (ECCE) and intraocular lens (IOL) implantation.
      SETTING: Department of Ophthalmology, University of Alicante, Spain. METHODS:
      Using a Kowa laser flare-cell meter, we measured cell and flare for 3 months
      postoperatively in 550 eyes of 435 consecutive patients who had uneventful ECCE
      and IOL implantation. We compared the results in terms of the type of IOL
      implanted. RESULTS: The amount of inflammation varied, but not significantly,
      according to the IOL type. The highest level of flare and cell always occurred
      the day following surgery regardless of which IOL was used. A small increase in
      flare was observed on the 30th day. CONCLUSION: Inflammation after uncomplicated
      ECCE, as measured with a laser flare-cell meter, resolved by 3 months and was not
      significantly affected by the type of IOL implanted. More sensitive instruments
      should be developed to measure inflammation immediately after surgery.

PMID- 9279672
TI  - Comparison of diclofenac sodium and flurbiprofen for inhibition of surgically
      induced miosis.
AB  - PURPOSE: To compare the efficacy of two topical nonsteroidal anti-inflammatory
      drugs, diclofenac sodium and flurbiprofen, commonly used prior to cataract
      surgery to inhibit surgically induced miosis. SETTING: Department of
      Ophthalmology, Cornell University Medical College, The New York Hospital, New
      York, New York. METHODS: Fifty-one patients having phacoemulsification were
      randomly assigned to receive topical treatment with either diclofenac sodium 0.1%
      or flurbiprofen 0.03% every 15 minutes for four doses along with their dilating
      drops beginning 1 hour before surgery. All surgeries were videotaped, with the
      magnification calibrated. The videotapes were analyzed and the horizontal and
      vertical diameters of the pupil were measured just before the initial
      conjunctival incision (baseline) and then every 5 minutes during the procedure.
      Measurements were also made at the beginning of capsulorhexis, the beginning of
      phacoemulsification, the end of phacoemulsification, the end of cortical cleanup,
      and before and after implantation of an intraocular lens. RESULTS: There was no
      statistically significant difference between the two treatment groups in baseline
      pupil dilation; however, regardless of the drug received, the light irides were,
      on average, more dilated at baseline than the dark ones. After surgery began,
      there were no statistically significant differences between the two groups at any
      time or surgical interval except at the start of phacoemulsification, at which
      point the flurbiprofen-treated eyes were more dilated than the diclofenac-treated
      eyes. CONCLUSION: Diclofenac sodium and flurbiprofen were equally effective in
      maintaining intraoperative mydriasis during cataract surgery.

PMID- 9279673
TI  - Efficacy and tolerance of diclofenac sodium 0.1%, flurbiprofen 0.03%, and
      indomethacin 1.0% in controlling postoperative inflammation.
AB  - PURPOSE: To compare the anti-inflammatory effect of diclofenac sodium 0.1%
      ophthalmic solution, flurbiprofen 0.03% ophthalmic solution, and indomethacin
      1.0%. SETTING: Department of Ophthalmology, University of Koln, and
      Bundesknappschaftskrankenhaus, Sulzbach, Germany. METHODS: One hundred seventeen
      patients enrolled in this prospective, randomized, double-masked, and parallel
      group study had phacoemulsification and intraocular lens implantation and
      received one of the three solutions. Preoperatively at day 1 and postoperatively
      at day 4 or 5 and day 12, 13, or 14, they were examined by slitlamp, applanation
      tonometry, and laser flare meter. RESULTS: Anterior chamber flare reduction from
      baseline was significantly greater in the diclofenac group than in the
      flurbiprofen group (P = .022). Patients in the diclofenac group had significantly
      less burning and stinging than those in the flurbiprofen and indomethacin groups
      at postoperative days 4-5 and 12-14 (P = .001). CONCLUSION: Diclofenac sodium
      appeared to be more potent than flurbiprofen in controlling intraocular
      inflammation after cataract surgery and appeared to be locally tolerated better
      than flurbiprofen and indomethacin.

PMID- 9279674
TI  - Effectiveness of diclofenac eyedrops in reducing inflammation and the incidence
      of cystoid macular edema after cataract surgery.
AB  - PURPOSE: To evaluate the effectiveness of diclofenac eyedrops in reducing
      inflammation and the incidence of angiographic cystoid macular edema (CME) after
      cataract surgery and intraocular lens (IOL) implantation. SETTING: Eye Clinic,
      Institute of Biomedical Sciences, San Paolo Hospital, Milan, Italy. METHODS:
      Eighty-eight patients having cataract extraction were enrolled in a randomized
      clinical trial: 42 were given diclofenac eyedrops and 46, placebo. Postoperative
      inflammation in both groups was graded for 6 months using a dedicated system.
      RESULTS: Eight patients (9%) had evidence of angiographic CME approximately 1
      month after surgery: seven of these were in the placebo group (P = .039). This
      difference was not significant 3 and 6 months postoperatively. The signs of
      ocular inflammation were greater in the eyes receiving placebo; the difference
      was particularly evident up to 1 week after surgery. There was no significant
      difference in visual acuity between the two groups at any follow-up point, but
      the contrast sensitivity of the eyes that received diclofenac improved
      significantly at 10.5 cycles per degree 1 month postoperatively. CONCLUSION:
      Diclofenac eyedrops effectively reduced ocular inflammation and the occurrence of
      angiographic CME after cataract surgery.

PMID- 9279675
TI  - Intraocular lens implantation in eyes with Fuchs' heterochromic iridocyclitis.
AB  - PURPOSE: To evaluate the results of cataract surgery with intraocular lens (IOL)
      implantation in eyes with Fuchs' heterochromic iridocyclitis. SETTING: Saint
      Victor Hospital, Amiens, France. METHODS: We reviewed the charts of 93 patients
      (94 eyes) with heterochromic iridocyclitis who had cataract extraction and IOL
      implantation by the same surgeon. In six patients, the IOL was placed in the
      anterior chamber; 9 received Binkhorst four-loop IOLs sutured at the 12 and 6
      o'clock positions, and 79 received posterior chamber IOLs, 15 in the sulcus and
      64 in the capsular bag. Follow-up was from 6 months to 10 years (mean 41 months).
      RESULTS: Precipitates on the IOL surface and white keratic precipitates were
      detected in 65.5% of eyes. Most eyes had minimal anterior segment activity. No
      severe uveitis was observed. The major problem, observed in 12.3% of the
      patients, was glaucoma. Best corrected postoperative visual acuity was 20/40 or
      better in 76.6% of eyes. CONCLUSION: Eyes with heterochromic iridocyclitis
      responded well to cataract extraction with IOL implantation. The restoration of
      satisfactory binocular vision justifies IOL implantation in patients with Fuchs'
      unilateral syndrome.

PMID- 9279676
TI  - Effect of intraocular sustained release of indomethacin on postoperative
      inflammation and posterior capsule opacification.
AB  - PURPOSE: To assess whether the sustained release of indomethacin significantly
      reduces postoperative inflammation and posterior capsule opacification (PCO).
      SETTING: Nishi Eye Hospital, Jinshikai Medical Foundation, Osaka, Japan. METHODS:
      A 7 mm diameter, 1 mm thick polylactic-polyglycolic acid disk containing 7 mg of
      indomethacin was implanted in five rabbit eyes after continuous curvilinear
      capsulorhexis and phacoemulsification. The disk and an IOL placed above it were
      implanted in the capsular bag. The contralateral eyes, which served as controls,
      received a disk without indomethacin and the same type IOL in the same manner.
      RESULTS: The indomethacin was fully released within 3 weeks in vitro, a release
      rate of about 14 micrograms/h. Postoperatively, aqueous flare intensity was
      significantly lower at days 2, 3, and 4 and at weeks 1, 2, and 3. Prostaglandin
      E2 was not detectable in the aqueous humor of the indomethacin-treated eyes on
      day 3 and at week 4. In the control eyes, mean concentration was 491 pg/ml +/- 54
      (SD) and 990 +/- 243 pg/ml, respectively. Histopathological examination showed no
      significant decrease in PCO. CONCLUSION: Although sustained release of
      indomethacin significantly decreased inflammation, it did not reduce PCO.

PMID- 9279678
TI  - Annexin V-coated intraocular lenses.
AB  - PURPOSE: To assess whether annexin V-coated poly(methyl methacrylate) (PMMA)
      intraocular lenses (IOLs) prevent postoperative inflammation in rabbit eyes.
      SETTING: Department of Ophthalmology, Hopital Purpan, Toulouse, France. METHODS:
      Thirteen IOLs coated with annexin V were implanted in 13 rabbit eyes; the
      contralateral eyes received uncoated IOLs. Postoperative fibrin was quantitated
      by daily slitlamp examination until the anterior chamber was completely clear.
      Results were analyzed using a Wilcoxon test. Ocular toxicity was evaluated by
      light and electron microscopy. RESULTS: Eyes with the annexin V-coated IOLs had
      less severe inflammation on the first postoperative day, and the inflammation
      resolved more quickly than in eyes with uncoated IOLs (P < .05). No annexin V was
      released postoperatively, nor were there signs of ocular toxicity. CONCLUSION:
      Annexin V-coated lenses effectively reduced postoperative inflammation in rabbit
      eyes.

PMID- 9279677
TI  - Cellular reaction on the anterior surface of poly(methyl methacrylate)
      intraocular lenses.
AB  - PURPOSE: To assess the cellular reaction on the anterior surface of poly(methyl
      methacrylate) (PMMA) intraocular lenses (IOLs) implanted by phacoemulsification
      with continuous curvilinear capsulorhexis (CCC) or by extracapsular cataract
      extraction (ECCE) with a linear capsulotomy. SETTING: Cataract and Refractive
      Surgery Research Unit. Department of Ophthalmology, St. Thomas' Hospital, London,
      United Kingdom. METHODS: To document morphology, topography, and severity of the
      cellular reaction, specular microscopy of the anterior IOL surface was performed
      at 1 day, 1 week, and 1 and 3 months postoperatively in two parallel groups of 31
      consecutive cataractous eyes operated on by phacoemulsification with CCC or by
      ECCE with a linear capsulotomy. RESULTS: The local tissue response consisted of a
      nonspecific foreign-body reaction to the IOL and a lens epithelial cell reaction.
      The foreign-body reaction was significantly less severe in the
      phacoemulsification group than in the ECCE group, and the number of IOLs without
      inflammatory cells was significantly higher. CONCLUSION: The foreign-body
      reaction to PMMA IOLs is significantly reduced when the lens is implanted by
      phacoemulsification with CCC. This could be of clinical benefit in high-risk eyes
      prone to the inflammatory complications of cataract surgery.

PMID- 9279679
TI  - In vivo study of cell reactions on poly(methyl methacrylate) intraocular lenses
      with different surface properties.
AB  - PURPOSE: To evaluate the biocompatibility of three poly(methyl methacrylate)
      (PMMA) intraocular lenses (IOLs) with different surface properties. SETTING:
      University Eye Clinic, Vienna, Austria. METHODS: Cell reactions on the surfaces
      of unmodified, heparin-surface-modified (HSM), and surface-passivated (SP) PMMA
      IOLs were documented in vivo using a Zeiss specular microscope. Risk factors for
      such reactions were also determined. RESULTS: During the first postoperative
      days, small round and spindle-shaped cells were found on all IOLs. Cell density
      was higher in eyes with increased postoperative inflammation. After several days,
      epithelioid and foreign-body giant cells were seen on some IOLs. Cells appeared
      significantly less often on the IOLs with hydrophilic surfaces (HSM) than on
      those with hydrophobic surfaces (unmodified, SP). CONCLUSION: The significantly
      lower incidence of foreign-body reactions on hydrophilic than on hydrophobic IOL
      surfaces is consistent with the results of previous studies on hydrogel and
      silicone IOLs.

PMID- 9279680
TI  - Effect of heparin-surface-modified poly(methyl methacrylate) intraocular lenses
      on the postoperative inflammation in an Asian population.
AB  - PURPOSE: To compare the efficacy of heparin-surface-modified (HSM), poly(methyl
      methacrylate) (PMMA) posterior chamber intraocular lenses (IOLs) with that of
      unmodified PMMA IOLs in reducing postoperative complications caused by
      inflammatory reactions after extracapsular cataract extraction in an Asian
      population. SETTING: Departments of Ophthalmology, University of Malaya, Kuala
      Lumpur, Malaysia, and Tan Tock Seng Hospital, Singapore. METHODS: In a
      randomized, double-blind study performed at two centers, 51 patients received an
      HSM PMMA lens and 48, an unmodified PMMA IOL. Cell and pigment deposits were
      evaluated by slitlamp at 1 to 6 days, 2 to 3 weeks, and 3 to 6 months
      postoperatively. RESULTS: Significantly more eyes with unmodified IOLs had
      inflammatory cell deposits than those with HSM IOLs at 3 to 6 months (P < .001)
      and 12 to 14 months (P = .018) postoperatively. The HSM group also had
      significantly fewer cell deposits per patient at these two follow-ups.
      Significantly more eyes in the non-HSM group had pigment deposits 3 to 6 months
      after surgery (P = .049). One year postoperatively, about 85% of patients in both
      groups had a best corrected visual acuity of 0.5 or better. CONCLUSION: Heparin
      surface modification significantly reduced the inflammatory response to PMMA IOLs
      in an Asian population for at least 12 to 14 months.

PMID- 9279681
TI  - Lens epithelial cell outgrowth and matrix formation on intraocular lenses in
      rabbit eyes.
AB  - PURPOSE: To evaluate the presence and distribution of lens epithelial cells
      (LECs) and extracellular matrix on intraocular lenses (IOLs) implanted in the
      capsular bag in rabbit eyes. SETTING: Department of Ophthalmology, Wakayama
      Medical College, Wakayama, Japan. METHODS: Five adult albino rabbits had
      phacoemulsification and IOL implantation in both eyes. Two or 11 months later,
      the animals were killed by intravenous pentobarbital. The IOLs were removed and
      observed under scanning and transmission electron microscopy. RESULTS: In
      addition to the macrophages and giant cells on the IOLs, all eyes had a monolayer
      of flattened cells growing out from the residual anterior lens capsule and a
      fibrous meshwork of extracellular matrix. Unlike those of a macrophagic origin,
      these cells had no central cytoplasmic elevation of nuclei and few cell surface
      microvilli and were considered to be proliferating LECs. CONCLUSION: Lens
      epithelial cells are involved in the eye's cellular reaction to IOLs and in the
      formation of extracellular matrix on IOLs. Further study of LEC behavior on IOLs
      should be done to improve IOL biocompatibility.

PMID- 9279682
TI  - Lens epithelial cell migration onto the posterior capsule in vitro.
AB  - PURPOSE: To investigate lens epithelial cell (LEC) proliferation on the posterior
      capsule in an in vitro model. SETTING: Department of Ophthalmology, Keio
      University School of Medicine, Tokyo, Japan. METHODS: We cultured the cells
      remaining on the postoperative capsular bag and expanded the capsule with an open
      poly(methyl methacrylate) ring to simulate actual postoperative conditions. Using
      human and rabbit cadaver eyes, we monitored the migration and proliferation of
      LECs onto the postoperative capsular bag by time-lapse videomicroscopy. RESULTS:
      The remaining viable cells migrated onto the posterior capsule through the
      equator and directly from the anterior capsule. The cells typically proliferated
      in a monolayer because of contact inhibition of cell movement and division, but
      they proliferated in a multilayer at some regions where nonviable cells had
      accumulated and there were capsular folds. CONCLUSION: A means to block both
      routes of cell expansion must be developed to prevent LEC migration onto the
      posterior capsule.

PMID- 9279684
TI  - Synthesis of interleukin-1, interleukin-6, and basic fibroblast growth factor by
      human cataract lens epithelial cells.
AB  - PURPOSE: To assay the following cytokines in an incubation medium of cultured
      lens epithelial cells (LECs) derived from human cataracts: interleukin-1 alpha
      (IL-1), interleukin (IL-6), basic fibroblast growth factor (b-FGF), tumor
      necrosis factor-alpha (TNF-alpha), and epidermal growth factor (EGF). SETTING:
      Nishi Eye Hospital, Jinshikai Medical Foundation, Osaka, Japan. METHODS: The
      anterior lens capsule with attached LECs was obtained by capsulotomy during
      cataract surgery and cultured. The incubation medium was changed on days 1 and 2
      of culture and thereafter weekly up to 7 weeks. The media collected from a
      specific number of cultures at each medium change were pooled and assayed for
      cytokines by enzyme-linked immunosorbent assay. RESULTS: Interleukin-1 alpha was
      detected in one of the two pools of the 2 week cultures (207 pg/10(6) cells), in
      two of the three pools of the 3 week cultures (120 pg/10(6) and 139 pg/10(6)
      cells), and in one of the two pools of the 4 week cultures (111 pg/10(6) cells).
      Interleukin-6 was detected in one pool of the 1 week cultures (195 pg/10(5)
      cells) and in one pool of the 7 week cultures (81.6 pg/10(5) cells). Basic FGF
      was detected in the incubation media from three series of samples during the
      culture time course: 87 pg/ml in the 1 day cultures in the first series; 478,
      310, and 269 pg/ml in the 1 day, 2 day, and 1 week cultures, respectively, in the
      second series; and 98 and 83 pg/ml in the 1 and 2 day cultures, respectively, in
      the third series. The TNF-alpha and EGF were not detected in any sample.
      CONCLUSION: After cataract surgery, IL-1, IL-6, and b-FGF may be produced in vivo
      by residual LECs, causing postoperative inflammation and LEC proliferation.

PMID- 9279683
TI  - Lens epithelial cell proliferation onto the intraocular lens optic in vitro.
AB  - PURPOSE: To determine how lens epithelial cells (LECs) proliferate onto an
      intraocular lens (IOL) after extracapsular cataract surgery. SETTING: Department
      of Ophthalmology, Keio University School of Medicine, Tokyo, Japan. METHODS: We
      cultured the capsular bags retaining LECs of eight human eye-bank eyes and six
      rabbit eyes that had had extracapsular lens extraction with in-the-bag
      implantation of a poly(methyl methacrylate) (PMMA) IOL and a PMMA ring. Cell
      proliferation onto the IOL optic was monitored by a time-lapse video system.
      RESULTS: Cells proliferated onto the IOL optic via the anterior capsulotomy
      margin, the inner surface of the anterior capsule, and the posterior capsule.
      They formed cell sheets similar to the membranes observed in clinical cases.
      CONCLUSIONS: Since the cells proliferated from the anterior capsule as well as
      from the posterior capsule onto the IOL optic, the membranes observed clinically
      on the IOL optic may be LEC sheets.

PMID- 9279685
TI  - Decreased prostaglandin E2 synthesis by lens epithelial cells cultured on heparin
      surface-modified poly(methyl methacrylate).
AB  - PURPOSE: To evaluate whether heparin surface modification reduces prostaglandin
      E2 (PGE2) synthesis by lens epithelial cells (LECs) after intraocular lens (IOL)
      implantation. SETTING: Nishi Eye Hospital, Jinshikai Medical Foundation, Osaka,
      Japan. METHODS: The prostaglandin E2 (PGE2) concentration was determined in an
      incubation medium of human cataract LECs cultured on heparin-surface-modified
      (HSM) poly(methyl methacrylate) (PMMA) plates at 1, 2, 3, and 4 weeks of culture.
      A medium without heparin served as a control. RESULTS: The PGE2 concentration was
      significantly lower in the HSM than in the control medium at 3 and 4 weeks of
      culture. CONCLUSION: The results are consistent with the clinical observation of
      significantly decreased inflammation in eyes with HSM IOLs, indicating that such
      modification increases PMMA's biocompatibility with LECs.

PMID- 9279686
TI  - Inhibition of migrating lens epithelial cells by sustained release of
      ethylenediaminetetraacetic acid.
AB  - PURPOSE: To evaluate the effect of the sustained-release of
      ethylenediaminetetraacetic acid (EDTA) chelating Ca++ on lens epithelial cell
      (LEC) migration. SETTING: Nishi Eye Hospital, Jinshikai Medical Foundation,
      Osaka, Japan. METHODS: Polylactic-glycolic acid disks containing 10% EDTA were
      placed in saline solution for about 2 weeks in vitro. About 60% (7
      micrograms/hour) of the EDTA was released during that time. The disks with a
      posterior chamber intraocular lens placed above were implanted in the capsular
      bag in five rabbit eyes after continuous curvilinear capsulorhexis and
      phacoemulsification. A disk without EDTA and the same lens type were placed in
      the bag in the contralateral eyes, which served as controls. RESULTS: After 2 to
      3 months, opacification in the central posterior capsule was significantly
      reduced in all eyes that received the disk with EDTA. CONCLUSION: The deprivation
      of Ca++ disrupted interaction between the posterior capsule and migrating LECs by
      inactivating the adhesion molecule integrin synthesized by LECs, significantly
      reducing LEC migration onto the posterior capsule.

PMID- 9279687
TI  - Experimental approaches for the treatment of murine B16 melanomas of various
      sizes. I: Local injection of ethanol with a combination of interleukin-2 or
      microwaval hyperthermia for B16 melanomas with a size of less than 7 mm in
      diameter.
AB  - The effects of local absolute ethanol injection combined with administration of
      interleukin-2 (IL-2) or microwaval hyperthermia in murine B16 melanomas with a
      size of approximately 7 mm in diameter were investigated. The groups of melanoma
      burdened mice treated with both local ethanol injection and local or intra
      abdominal administration of IL-2 showed clear suppression of any recurrence of
      melanoma once the melanomas had been destroyed by ethanol injection and a
      concomitant prolongation of the survival times. Also, local injection of ethanol
      in combination with local microwaval hyperthermia at 43 degrees C for 15 min
      twice a week caused complete cures in B16 melanomas with a size of less than 7 mm
      in diameter. The infiltrations of T lymphocytes and NK cells were augmented in
      the melanomas treated with ethanol injection and local injection of IL-2.
      However, the melanomas treated with ethanol injection and intra-abdominal
      injection of IL-2 hardly showed any infiltration of such immune cells, although
      the growth of melanomas was effectively suppressed. In the case of treatment with
      ethanol and hyperthermia, slight infiltration of NK cells was observed in the
      melanoma nests as well as in the interstitials. Thus, the direct injection of
      absolute ethanol in combination with IL-2 or microwaval hyperthermia is effective
      or even curative in the treatment of murine B16 melanomas with a size of less
      than 7 mm in diameter.

PMID- 9279688
TI  - Experimental approaches for the treatment of murine B16 melanomas of various
      sizes. II: Injection of ethanol with combinations of beta-interferon and
      microwaval hyperthermia for B16 melanomas with a size of greater than 10 mm in
      diameter.
AB  - Although ethanol injection in combination with microwaval hyperthermia and
      systemic administration of interleukin-2 was found to be very effective in
      suppressing the growth of B16 melanoma nodules with a size of less than 7 mm in
      diameter in our previous experiments, the growth of B16 melanomas with a size of
      greater than 10 mm in diameter was very difficult to control with any of the
      therapeutic modalities examined. In subsequent experiments, we investigated
      whether ethanol injection (150 microliters/injection) in combination with local
      injection of beta-interferon (2 x 10(4) IU/injection) and local microwaval
      hyperthermia at 43 degrees C for 15 min was able to suppress the growth of
      melanoma nodules and to prolong survival times of melanoma-burdened mice. The
      results were that we successfully suppressed the growth of melanoma nodules of
      that size for the first time with combinations of the therapeutic modalities
      described above. Infiltration of immunocompetent cells such as T lymphocytes and
      NK cells was clearly observed in the melanoma tissues treated with the
      therapeutic combination. These experimental results should be applied to the
      treatment of human melanomas in advanced stages which have no indications for
      surgical operation.

PMID- 9279689
TI  - Eosinophil cationic protein (ECP) level and its correlation with eosinophil
      number or IgE level of peripheral blood in patients with various skin diseases.
AB  - Eosinophil cationic protein (ECP) is a cationic protein derived from eosinophil
      granulocytes, and has been studied mainly in atopic diseases and considered as a
      useful marker of disease activity in atopic dermatitis. We measured the serum ECP
      levels in patients with various skin diseases (n = 875) and in normal healthy
      controls (n = 79), and evaluated the correlation between ECP level and blood
      eosinophil number, or ECP and IgE levels. Serum ECP levels were significantly
      higher in patients with drug eruption (15.8 +/- 1.7 micrograms/l), psoriasis
      (15.1 +/- 6.0 micrograms/l), acute urticaria (13.9 +/- 1.4 micrograms/l) than in
      healthy controls (4.5 +/- 0.3 micrograms/l) (P < 0.05) and also significantly
      elevated in patients with elevated eosinophil numbers (15.2 +/- 1.0 micrograms/l)
      compared to those in patients with normal eosinophil numbers (8.8 +/- 0.3
      micrograms/l) (P < 0.001). Serum ECP level and eosinophil number in peripheral
      blood were also correlated in patients with psoriasis (gamma = 0.82, P < 0.01),
      drug eruption (gamma = 0.31, P < 0.01) and acute urticaria (gamma = 0.20, P <
      0.05). However, no correlation between ECP and IgE levels in all of the patients
      was found. Among the patients with chronic urticaria, ECP levels showed an
      increasing trend in patients with angioedema, cold urticaria and dermographic
      urticaria as compared with those in healthy controls. Our results suggest that,
      even though the role of ECP released from activated eosinophils is still unknown,
      its measurement might be of help to understand the pathogenesis of some skin
      disorders.

PMID- 9279690
TI  - Differential regulations of matrix metalloproteinases and tissue inhibitors of
      metalloproteinases in dermal fibroblasts by dibutyril cyclic AMP.
AB  - The influence of dibutyril cyclic AMP (dbcAMP) on the gene expression of matrix
      metalloproteinases (MMP)-1, MMP-2, MMP-3, tissue inhibitors of metalloproteinases
      (TIMP)-1 and TIMP-2 was investigated in human skin fibroblasts by northern
      analyses. The treatment of dbcAMP increased MMP-1 and MMP-3 mRNA levels but
      decreased TIMP-1 mRNA levels in time and dose dependent manners. Procollagen
      alpha 1 (I), MMP-2 and TIMP-2 mRNA levels were unaltered by this reagent. Our
      data indicate that dbcAMP potentially enhances the degradation of extracellular
      components of connective tissue.

PMID- 9279691
TI  - Can urinary nitrite results be used to guide antimicrobial choice for urinary
      tract infection?
AB  - Enterococcus is unable to reduce nitrates and is also considered clinically
      resistant to trimethoprim/sulfamethoxazole (TMP/SMX), the drug of choice for
      uncomplicated urinary tract infection (UTI). The purpose of this study was to
      determine whether urinalysis nitrite results can be used to guide antimicrobial
      therapy when treating UTI in the emergency department (ED). A retrospective chart
      review examined 159 university hospital ED outpatients who had signs or symptoms
      of UTI and had a urinalysis with positive culture. Patients were categorized into
      two groups based on nitrite results. The proportion of isolates sensitive to
      TMP/SMX in each group was compared by using a two-sample z-test. Eighty-six
      urinalyses were nitrite positive: 67 (78%) contained TMP/SMX-sensitive isolates.
      Seventy-three urinalyses were nitrite negative; 60 (82%) contained sensitive
      isolates. There was no statistically significant difference in the proportion of
      isolates sensitive to TMP/SMX. Thus, we conclude that emergency physicians should
      not adjust antibiotic therapy for UTI based on nitrite results.

PMID- 9279692
TI  - Fluoxetine versus tricyclic antidepressants: a prospective multicenter study of
      antidepressant drug overdoses. The Antidepressant Study Group.
AB  - This study compares the clinical course of tricyclic antidepressant and
      fluoxetine overdose. The study was a prospective case series of 9 urban hospital
      systems. Consecutive sampling of overdose patients presenting to emergency
      departments provided the participants for the study. The therapy was determined
      by each institution. Clinical, laboratory, economic impact, and coroners'
      information was gathered. Of 622 patients, 482 were excluded because of
      significant coingestants or lack of laboratory confirmation, leaving 124
      tricyclic antidepressant and 16 fluoxetine cases. Twenty-seven percent of
      tricyclic antidepressant patients were alert on arrival to the emergency
      department; only 12.9% remained alert. The following were significantly more
      frequent after tricyclic antidepressant overdose: agitation, tachycardia, QRS
      prolongation, terminal R-wave deviation, intubation, coma, and admission to the
      intensive care unit. The mean tricyclic plus metabolite level was 777.6 ng/mL
      (range = 20-5260 ng/ mL), and the mean fluoxetine plus metabolite level was 496.4
      ng/mL (range = 120-1930 ng/mL). There were two tricyclic antidepressant deaths.
      Of 179 total drug-ingestion deaths from the coroners' records, 38 were from
      tricyclic antidepressants and none from fluoxetine. Thus, tricyclic
      antidepressant overdoses resulted in more toxicity and more frequent admissions
      to the intensive care unit than did fluoxetine overdoses.

PMID- 9279693
TI  - Domestic violence in the emergency department: how do women prefer to disclose
      and discuss the issues?
AB  - The purpose of this study was to survey women presenting to the emergency
      department (ED) and determine from them how best to identify and discuss issues
      of domestic violence (DV). An anonymous 10-question survey was given to
      ambulatory females presenting to the ED. It was conducted at two affiliated
      university hospital EDs, one an urban trauma center (ED 1) and the other an ED in
      an affluent suburban setting (ED 2). Two hundred forty-three women responded (73%
      response), 153 (63%) from ED 1 and 90 (37%) from ED 2. There were 21 women (9%)
      currently being abused, and 109 (45%) were past victims. Of all victims, 40 (36%)
      would only divulge DV if asked directly, 28 (25%) would volunteer this
      information without being asked, and 12 (11%) would not report DV even if asked.
      Of women who would reveal DV only if asked directly, 52 (45%) felt very
      comfortable disclosing this to an ED physician, although only 27 (24%) would
      reveal DV at a triage encounter. Of past or current victims, 43 (39%) would not
      disclose DV if they knew that ED personnel were required to report it. In
      conclusion, the ED is an appropriate setting to discuss DV issues. A significant
      percentage of women will disclose DV only if asked directly about it. Many
      victims of DV feel very comfortable discussing DV with ED physicians and nurses,
      although they may be less likely to reveal DV incidents at a triage encounter.
      Mandatory reporting laws may be an impediment to identifying cases of abuse.

PMID- 9279694
TI  - Utilizing clinical factors to reduce head CT scan ordering for minor head trauma
      patients.
AB  - Our study objective was to determine whether simple clinical criteria can be used
      to safely reduce the number of patients who require cranial computed tomography
      (CT) scan after sustaining minor head trauma. Awake patients (Glascow Coma Scale
      = 15) who presented to the emergency department with acute head injury associated
      with a loss of consciousness were evaluated for clinical predictors of head
      injury prior to CT scan. The studied risk factors included severe headache,
      nausea, vomiting, and depressed skull fracture on physical examination. Patients
      with no risk factors present were compared with patients with one or more risk
      factors with respect to abnormal CT rate and rate of operative intervention for
      head injury. Of the 2143 patients entered into the study, 1302 (61%) had no risk
      factor for head injury, whereas 841 (39%) had one or more risk factors present. A
      total of 138 (6.4%) of those studied had an abnormal CT scan. This number
      included 3.7% of those patients with no risk factors vs. 11% in patients with one
      or more risk factors. The CT scan abnormalities in the no-risk-factor group were
      not clinically significant. All 5 patients who required operative intervention
      had at least one of the risk factors present. The use of four simple clinical
      criteria in minor head trauma patients would allow a 61% reduction in the number
      of head CT scans performed and still identify all patients who require
      neurosurgical intervention and the majority of patients with an abnormal CT scan.
      This method could lead to a large savings in patient charges nationwide. Further
      studies may be helpful in confirming these findings.

PMID- 9279695
TI  - Performance of two clinical decision rules for knee radiography.
AB  - We designed a prospective observational study to attempt to validate two recently
      described clinical decision rules for knee radiography. Consecutive patients aged
      > or = 15 yr with acute knee injuries occurring less than 1 wk prior to
      presentation were included for study. Patients with distracting conditions, open
      knee injuries, or previous surgery were excluded. Each patient was assessed for 7
      historical and 15 physical examination criteria that were recorded on a
      standardized data collection instrument. Radiographs were ordered at the
      discretion of the attending physician and were read by two board-certified
      radiologists. When radiographs were not ordered, structured telephone follow-up
      was performed after 3 wk. The main outcome parameter was the presence or absence
      of a clinically significant fracture. There were 351 patients in the study; 26
      (7%) had knee fractures. Fractures were significantly associated with an
      increased prevalence for two of the three criteria in the rule derived by Bauer:
      inability to weight bear immediately or in the emergency department (ED; 76.9% of
      patients with a fracture vs. 29.8% of patients without a fracture) and effusion
      (53.8% vs. 28.9%, respectively). Ecchymosis was not significantly associated with
      fracture (19.2% with fracture vs. 9% with no fracture). Use of the Bauer rule
      would have led to a radiographic evaluation of 22 of the 26 patients with knee
      fractures (sensitivity = 84.6%, specificity = 48.9%). Fractures were associated
      with a significantly increased prevalence for three of the five criteria in the
      decision rule proposed by Stiell: isolated patella tenderness (30.8% with
      fracture vs. 14.5% with no fracture), inability to flex the knee to 90 degrees
      (42.3% vs. 19.7%, respectively), and inability to weight bear immediately and in
      the ED (57.7% vs. 18.8%, respectively). Age > or = 55 yr (23.1% vs. 12.0%,
      respectively) and fibula head tenderness (11.5% vs. 5.5%, respectively) were not
      significantly associated with fracture. Use of the Stiell rule would have led to
      radiographic evaluation of 22 of the 26 patients with knee fractures (sensitivity
      = 84.6%, specificity = 49.8%). We conclude that neither clinical decision rule is
      100% sensitive. Further refinement will be necessary to identify all patients
      with knee fractures.

PMID- 9279696
TI  - Carbon monoxide poisoning during ice storms: a tale of two cities.
AB  - This is a retrospective case series conducted at two university hospital
      emergency departments of 68 patients with a discharge diagnosis of carbon
      monoxide (CO) poisoning presenting during two different ice storms (March 1991
      and February 1994) in two cities (Rochester, NY, and Nashville, TN). Fifty-five
      patients were seen over 10 d in Rochester and 13 patients over 4 d in Nashville.
      The main sources of CO exposure were the indoor use of gasoline generators (40
      patients), propane or kerosene heaters (9 patients), and charcoal grills (8
      patients). Six patients did not speak English fluently (5 Asian patients in
      Nashville and 1 Greek patient in Rochester). The use of charcoal grills was the
      most common CO source in Nashville, occurring exclusively in patients of Asian
      descent, 5 of whom did not speak English. In Rochester, the use of gas generators
      was the most common CO source. Ice storms represent a significant threat to
      populations affected by prolonged power outages. Different cities will be
      affected in different ways. When ice storms occur, the media should distribute
      information about potential sources of CO exposure. In some cases, the message
      may need to be distributed by alternative methods to populations who do not speak
      English or do not have access to mainstream media.

PMID- 9279697
TI  - Epidemic carbon monoxide poisoning following a winter storm.
AB  - Hospital emergency departments were surveyed to estimate the number of patients
      treated for carbon monoxide (CO) poisoning after a severe winter storm disrupted
      electrical service in western Washington State. At least 81 persons were treated.
      The two main sources of CO were charcoal briquettes (54% of cases) and gasoline
      powered electrical generators (40% of cases). Of the 44 persons affected by CO
      from burning charcoal, 40 (91%) were members of ethnic minority groups; 27 did
      not speak English. All persons affected by CO from generators were non-Hispanic
      Whites. This was the largest epidemic of storm-related CO poisoning reported in
      the United States. This epidemic demonstrated the need to anticipate CO poisoning
      as a possible consequence of winter storms in cold climates and to make
      preventive messages understandable to the entire population at risk, including
      those persons who do not understand written or spoken English.

PMID- 9279698
TI  - Facial nerve paresis involving passenger airbag deployment: a case report.
AB  - The case of a 32-yr-old woman who developed transient facial nerve paresis
      following deployment of the passenger airbag is presented. Although a wide range
      of injuries including fatalities have occurred, this case represents a unique
      type of injury following passenger airbag deployment.

PMID- 9279699
TI  - Multiphasic anaphylaxis: report of a case with prehospital and emergency
      department considerations.
AB  - Anaphylaxis, a multisystem allergic reaction, represents a true medical
      emergency. Anaphylaxis is characterized by a combination of the following
      symptoms: urticaria, angioedema, distributive shock, and respiratory failure.
      Most often, the patient is rapidly treated with prompt resolution of the
      anaphylaxis in either the out-of-hospital or emergency department (ED) setting.
      Infrequently, recurrent or multiphasic anaphylaxis is encountered, involving a
      reappearance of allergic phenomena after complete resolution of the original
      reaction. Recurrence may involve nuisance-level issues such as urticaria;
      alternatively, multiphasic reactions may be characterized by cardiovascular
      collapse or respiratory compromise. Initially aggressive pharmacological therapy
      followed by prolonged observation in either the ED or the in-hospital setting is
      strongly recommended to monitor for potential recurrence.

PMID- 9279701
TI  - Endobronchial cockroach: an unusual foreign body aspiration.
AB  - Foreign-body aspiration is a frequent and potentially lethal occurrence in
      children. It is associated with a variety of symptoms including choking,
      coughing, and wheezing. These symptoms differ in severity and are sometimes
      absent, and chest radiograph findings are often nonspecific. Thus, the diagnosis
      of foreign body aspiration is occasionally missed or delayed. A multitude of
      aspirated objects have been reported in the literature. In the present report, we
      describe the aspiration of a cockroach by a child with a delay in diagnosis of 3
      d.

PMID- 9279700
TI  - Thermal epiglottitis in adults: a new complication of illicit drug use.
AB  - Four cases of acute epiglottitis due to thermal injury were identified in a
      larger study of 407 cases of epiglottitis in Rhode Island from 1975 through 1992.
      All occurred in young adults (aged 22-33 yr) and were caused by the inhalation of
      heated objects when smoking illicit drugs (a tip of a marijuana cigarette in 1
      case and metal pieces from crack cocaine pipes in 3 cases). Symptoms, signs, and
      X-ray and laryngoscopic findings were similar to infectious epiglottitis. All
      recovered with observation and intravenous antibiotics; none required intubation.
      Emergency physicians should be aware of this etiology when managing young adults
      who present with acute epiglottitis.

PMID- 9279703
TI  - Search for a scientific basis for continuous suture closure: a 30-yr odyssey.
AB  - Continuous percutaneous and dermal suture closures have an important role in the
      approximation of long, linear lacerations in the emergency department. This
      report documents the scientific basis for these continuous closure techniques. In
      addition, a detailed description of these surgical closure techniques is
      presented.

PMID- 9279702
TI  - Isolated venlafaxine-induced serotonin syndrome.
AB  - Serotonin syndrome is a potentially fatal complication of serotonergic drug
      therapy. Usually, serotonin syndrome occurs with the concomitant use of two
      serotonergic drugs; this case report describes a patient with a classic
      presentation of serotonin syndrome induced solely by a venlafaxine overdose.
      Emergency physicians need to be aware that the serotonin syndrome may occur not
      only with serotonergic drug combinations but also with overdoses of a single
      potent serotonergic agent such as venlafaxine.

PMID- 9279704
TI  - Technical considerations in knot construction. Part II. Interrupted dermal suture
      closure.
AB  - The purpose of this study was to identify the optimal knot construction for
      interrupted dermal sutures. A synthetic braided absorbable suture, sizes 3-0 and
      5-0, was selected for this evaluation. With reproducible mechanical performance
      tests, we determined that the construction of secure knots without ears required
      one additional throw as compared with secure knots with 3-mm ears. The direction
      of applied tension did not alter knot security, with the exception of granny
      knots, which required an extra throw when tension was applied parallel to the
      suture loop. Because interrupted dermal knot construction is accomplished without
      knot ears and with an applied tension parallel to the wound, one additional throw
      must be added to the knot to ensure knot security.

PMID- 9279705
TI  - Doxapram in hypercapnic chronic obstructive pulmonary disease with respiratory
      failure.
AB  - An 81-yr-old man with severe chronic obstructive pulmonary disease and
      hypercapnia presented to the emergency department (ED) obtunded and in acute
      respiratory distress. He had instructed his family to refuse intubation but
      agreed to all other measures to sustain his life. Treatment measures included the
      administration of intravenous doxapram, which was followed promptly by a marked
      improvement in his respiratory function and mentation. Respiratory stimulants may
      be useful as a temporizing measure in this difficult ED therapeutic problem.

PMID- 9279706
TI  - Intermittent abdominal pain in a middle-aged man.

PMID- 9279707
TI  - Chest pain in an elderly patient.

PMID- 9279708
TI  - Edlich drive: a metaphor for the Edlich tradition.
AB  - Richard F. Edlich, MD, the Raymond F. Morgan Professor of Plastic Surgery and
      Professor of Biomedical Engineering, has been honored with the naming of a new
      road at North Fork Business Park: Edlich Drive. North Fork Business Park is a
      high-technology center for biomedical research, and the designation of this new
      road celebrates Dr. Edlich's instrumental role in the formation of a successful
      partnership between the University of Virginia and private industry. This
      partnership provides a mechanism to move technology from the laboratory to the
      marketplace and, ultimately, to the patient's bedside. Dr. Edlich's unparalleled
      contributions to his community include the establishment of the Emergency
      Department at the University of Virginia, the implementation of a regional
      emergency medical system, and the development of the Pegasus Emergency Flight
      Operations. Other accomplishments include the founding of the Ira DeCamp Regional
      Burn Center and the Department of Rehabilitation Medicine. "Drive" aptly
      characterizes Dr. Edlich's unfailing commitment to his many roles as physician,
      research scientist, community leader, and mentor for medical students and
      residents.

PMID- 9279709
TI  - Winter storms and great imitators.

PMID- 9279710
TI  - Extortion in the emergency department.

PMID- 9279711
TI  - Asthma guidelines--beyond physician behavior.

PMID- 9279712
TI  - Aphorisms.

PMID- 9279713
TI  - Extortion in the emergency department.
AB  - We present the case of a 33-yr-old female patient who, along with members of her
      family, attempted to extort approximately $6000.00 from our institution and her
      insurance company. This attempted extortion was done under the guise of a missed
      retained foreign body. The patient initially presented to our emergency
      department with a laceration to her right forearm; X-ray studies obtained after
      the wound had been sutured revealed no foreign body. Several days later, the
      patient and family members approached our administrative staff demanding
      recompense for metal fragments discovered in the patient's wound at another
      facility. Comparison of radiographs revealed that the metallic fragments were
      placed in the wound after she was treated and released from our emergency
      department, and monetary compensation was denied.

PMID- 9279714
TI  - Management of acute asthma in Canada: an assessment of emergency physician
      behaviour.
AB  - The study objective was to assess Canadian emergency physicians for their
      management preferences and their compliance with recently developed guidelines
      for treatment of acute asthma in adults. The design was a cross-sectional survey
      sent to members of the Canadian Association of Emergency Physicians (CAEP) and to
      the emergency department (ED) directors of all Canadian hospitals with more than
      25 beds in November 1992. ED directors who had not responded were sent a second
      survey in January 1993. The response rates for the survey were 60.1% (362/602)
      for ED directors and 53.4% (302/586) for CAEP members. Respondents were more
      likely to be from larger hospitals and to have completed some training beyond
      general practice level (CCFP, CCFP-EM, ABEM, FRCPC). There were wide variations
      among respondents in the use of objective measurements of asthma severity (forced
      expiratory volume in 1 s [FEV1] and peak expiratory flow rates [PEFR]), dosing of
      bronchodilators, and utilization of systemic corticosteroids. Forty-six percent
      of respondents used the FEV1 "occasionally" (22.3%) or "never" (23.8%), and 26.7%
      used PEFR "occasionally" (15.8%) or "never" (10.9%) in asthma management. Ninety
      seven percent used nebulized beta agonist "always" (71.3%) or "often" (25.6%),
      but only 48.5% used the metered dose inhaler (MDI) "always" (11%) or "often"
      (37.5%). More than a quarter of respondents (27.2%) used doses of beta agonists
      that were less than those recommended (> every 30-60 min). Oral corticosteroids
      were prescribed at discharge only "occasionally" (51.1%), "seldom" (18.9%), or
      "never" (6.5%) in 76.6% of physicians. Physicians with more training were more
      likely to assess and treat patients according to current asthma treatment
      guidelines. The survey shows that many Canadian emergency physicians did not
      follow published recommendations for the care of patients with acute asthma. This
      finding was especially so with regard to objective evaluation of airflow,
      aggressive use of beta-agonists, the use of corticosteroids, and in making
      appropriate arrangements for patient discharge and follow-up.

PMID- 9279715
TI  - Clinical activities during a clerkship rotation in emergency medicine.
AB  - Clinical log books were completed by the 1995-1996 clinical clerks at Queen's
      University, Kingston, Ontario, Canada, during their 2-wk rotation in emergency
      medicine. To determine the clinical activities of the students and assess the
      educational effectiveness of our clerkship program, the information recorded in
      these log books was compared with the results of a survey of the emergency
      department (ED) staff physicians. This survey asked the physicians to identify
      five essential clinical presentations and procedural skills that they felt the
      clerks must observe during their rotation in the ED. To our knowledge, this is
      the first Canadian report using log books as a quality assurance tool for a
      clerkship program in emergency medicine. This study has highlighted specific
      weaknesses in the clinical activities of the clerks and will serve as a valuable
      resource for future assessments of the emergency medicine rotation at our
      institution.

PMID- 9279716
TI  - Low-molecular-weight heparin in the emergency department treatment of venous
      thromboembolism.
AB  - Accepted initial therapy for deep vein thrombosis (DVT) is intravenous heparin
      infusion, which requires hospitalization, inhibits patient ambulation, consumes
      nursing time, and generates laboratory cost. The effects of heparin are
      unpredictable, and maintaining optimal anti-coagulation requires careful
      laboratory monitoring. Many patients are underdosed and 5-20% of heparin-treated
      patients suffer hemorrhagic complications. Low-molecular-weight (LMW) heparins
      have a predictable anticoagulant response, require no laboratory monitoring, and
      can be administered once or twice daily by subcutaneous injection, thus
      facilitating outpatient treatment. LMW heparins are at least as safe and
      effective as standard intravenous heparin for the treatment of uncomplicated DVT.
      LMW heparin use is associated with decreased admission rates, shorter lengths of
      stay, decreased nursing time, better patient quality of life, and lower
      laboratory costs. In our emergency department, we have adopted a LMW heparin
      protocol for the outpatient treatment of suspected or proven DVT.

PMID- 9279717
TI  - Aspects of prosthetic valve endocarditis.

PMID- 9279718
TI  - Serum Aspergillus galactomannan antigen testing by sandwich ELISA: practical use
      in neutropenic patients.
AB  - The double sandwich ELISA detecting Aspergillus galactomannan (GM) was
      prospectively evaluated for the diagnosis of invasive aspergillosis (IA) in 50
      haematological patients at risk for IA. Serum samples were collected once weekly
      as long as the risk factors persisted. Six patients had proven or probable IA (3
      A. fumigatus, 1 A. flavus, 1 A. niger, 1 A. ustus) and the GM titres were
      parallel to the clinical evolution of IA. Six of nine patients with suspected IA
      had at least two consecutive serum GM titres above 1 ng/ml and died with
      increasing titres, whereas the GM-negative patients survived. Positive GM titres
      did not anticipate the isolation of fungi. Unfortunately, positive GM titres did
      not anticipate the initiation of antifungal therapy, based on clinical suspicion.
      Moreover, if a true-positive result was defined as two consecutive positive serum
      samples, four patients out of 35 without proven, probable or suspected IA were
      positive. Then, the rate of false-positive results was high (12%) in the range
      previously reported. Nevertheless, the GM ELISA appears useful to assess IA and
      to follow the efficacy of antifungal treatment.

PMID- 9279719
TI  - Analysis of 5 years of bacteraemias: importance of stratification of microbial
      susceptibilities by source of patients.
AB  - Many factors need to be considered when selecting empiric antimicrobial treatment
      for infections; foremost are the principal pathogens causing the diagnosed
      infection and their antimicrobial susceptibility patterns. These susceptibilities
      are location specific. This study analyses blood cultures of a 5-year period
      (1990-94) at a 550 bed community hospital and stratifies antimicrobial
      susceptibilities by source of patients. Data included: date of culture, patient
      location, number of positive bottles with the same organism over a period of 2
      weeks and results of susceptibility testing. Positive cultures from patients in
      the Emergency Department were deemed to reflect community-acquired strains:
      positive cultures from patients in the Intensive Care Unit were considered
      nosocomial organisms. During the study period 52055 blood cultures were drawn;
      5652 (11%) from 2742 patients grew at least one organism, excluding skin
      contaminants. Organisms cultured most frequently were: Enterobacteriaceae: 1162
      patients (42%); Staphylococcus aureus: 442 (16%); Enterococcus; 429 (16%); and
      Pseudomonas: 196 (7%). Antimicrobial susceptibility percentages of
      Enterobacteriaceae from Emergency Room patients (n = 370) were significantly
      greater to all tested antimicrobials than from ICC patients (n = 161) (P <
      0.001). Overall, 143 isolates of S. aureus from 442 patients (32%) were
      methicillin resistant (MR); stratification by department revealed a range of
      20/142 (14%) MR in community acquired strains to 49/67 (73%) from ICU patients (P
      < 0.001). Detailed tables with antimicrobial susceptibilities according to
      strains, and stratified by source of patients are presented. When selecting
      empiric antimicrobial therapy for patients with bacterial infections, it is
      crucially important to physicians to have access to antimicrobial susceptibility
      percentages, stratified by source of patients.

PMID- 9279720
TI  - Behaviour of IgG antibody avidity for the antigen and of IgA antibody in active
      cytomegalovirus, Epstein-Barr virus, herpes simplex virus and human herpes virus
      6 infections. Adaptation of a commercial test.
AB  - The clinical value of specific IgA and IgG antibody avidity to herpes simplex
      virus, cytomegalovirus, Epstein-Barr virus and human herpes virus 6 for the
      detection of active disease and primary infection, respectively, was evaluated.
      The IgG avidity test, with a break point of 55%, for the detection of primary
      infection, and of the IgA test for the detection of disease, were associated with
      a sensitivity of 97% and 64%, respectively; specificity of 100% and 82%; a
      positive predictive value of 100% and 76%; and a negative predictive value of 96%
      and 72%, respectively.

PMID- 9279721
TI  - The impact of HIV infection on lactose absorptive capacity.
AB  - Forty HIV-infected adult patients at different disease stages and 44 healthy
      volunteers were evaluated for lactose malabsorption using the hydrogen breath
      test after 20 g lactose ingestion. All subjects were previously tested for breath
      hydrogen (H2) excretion after 12 g lactulose ingestion. The presence of
      intestinal superinfections, gastrointestinal symptoms and the intensity of
      clinical intolerance after lactose load were accurately searched in each patient.
      The cumulative H2 excretion after lactulose did not significantly differ between
      the different groups studied. The prevalence of lactose malabsorption turned out
      to be significantly higher (P < 0.001) in HIV-infected patients (70%) than in
      controls (34%). Moreover, in patients in more advanced disease stages the degree
      of lactose malabsorption was significantly greater than in patients at earlier
      disease stages, who did not differ from healthy volunteers. Furthermore the
      degree of lactose intolerance was significantly greater (P < 0.001) in
      symptomatic patients than in those without intestinal symptoms and in healthy
      volunteers, while no significant difference was observed between these latter
      groups. The results here demonstrate the negative impact of HIV infection on
      lactose absorptive capacity in adult patients, particularly marked in more
      advanced stages of the disease, suggesting that, in addition to the presence of
      the virus alone, other factors may contribute to determine the enterokinetic
      alterations responsible for lactase deficiency.

PMID- 9279722
TI  - Early appearance of neutralizing antibodies after vaccination with an inactivated
      hepatitis A vaccine.
AB  - Sera from 30 subjects vaccinated with the Pasteur Merieux Serums & Vaccins (PM)
      inactivated hepatitis A vaccine, and from 30 subjects vaccinated with the
      Smithkline Beecham (SB) inactivated hepatitis A vaccine, were tested in two
      laboratories in order to provide comparative data on neutralizing activities of
      vaccine-induced antibodies. Sera were also evaluated by a modified
      radioimmunoassay (mRIA) and results were compared to neutralization assays
      results. Neutralizing antibody titres provided by the two laboratories correlated
      well (coefficient or correlation 0.42, P < 0.001). Neutralizing antibodies were
      detected after vaccination with both vaccines, and the kinetics of neutralizing
      antibody were the same with both vaccines. The titres gradually increased between
      the second week after the first dose and the post-booster dose (week 28). A
      strong booster effect of the booster vaccine dose on neutralizing titres was
      observed. Significantly higher neutralizing antibody titres with the PM vaccine
      were observed as early immune response on week 2 titres on both series of
      results. Vaccine-induced neutralizing antibody titres and vaccine-induced
      antibody mRIA titres correlated well (coefficient of correlation 0.82 and 0.72,
      respectively, P < 0.0001 in both cases). These results demonstrate early
      appearance of neutralizing antibody at high titre with the PM vaccine.

PMID- 9279724
TI  - The investigation of toxoplasma infection associated with pregnancy.
AB  - An audit was undertaken to determine case compliance with prenatal testing and
      investigation of infants for toxoplasma infection. Subsequently, the effect of
      enhanced reference unit Intervention was studied. The proportion of cases of
      toxoplasma infection associated with pregnancy completing an investigation
      programme was calculated. The effect of continued and short-term additional
      intervention was assessed and reasons for failure to comply were sought. The
      status of the child was established in 30% of cases when acute maternal
      toxoplasma infection was detected. Continuous reference unit intervention
      significantly improved case compliance to 45% over a 3-year period, but the
      effect was lost when the additional measures were withdrawn. Failure to complete
      the investigation procedure was associated with loss of patient-clinician contact
      and clinician/laboratory error. Enhanced intervention did not result in a
      significant improvement in compliance with the investigation programme for babies
      with clinical abnormality. The benefits of testing for toxoplasma infection
      associated with pregnancy are limited by failure to complete necessary
      investigations.

PMID- 9279723
TI  - Procalcitonin as a marker of bacterial sepsis in patients infected with HIV-1.
AB  - Procalcitonin (ProCT) is a recently described marker of severe sepsis. It was
      decided to assess the value of proCT as a marker of secondary infection in
      patients infected with HIV-1. ProCT plasma levels were measured by
      immunoluminometric assay in a prospective study in 155 HIV-infected individuals:
      102 asymptomatic and 53 with lever or suspected secondary infections. The
      baseline plasma level of ProCT was low (0.5 ng/ml +/- 0.37), even in the latest
      stages of the disease, and did not differ from the values of healthy subjects
      (0.54 ng/ml +/- 0.08). EDTA-treated whole blood was collected from patients
      before starting specific antimicrobial therapy. No elevation of ProCT level was
      detected in HIV-infected patients with evolving secondary infections including
      PCP (n = 4), cerebral toxoplasmosis (n = 4), viral infections (n = 9),
      mycobacterial infections (n = 5), localized bacterial (n = 12) and fungal
      infections (n = 4), malignancies (n = 3), and in various associated infectious
      and non-infectious febrile events (n = 13). All these plasma values were lower
      than 2.1 ng/ml. In contrast, high ProCT plasma levels were detected in one HIV
      infected patient with a septicaemic Haemophilus influenzae infection (16.5 ng/ml)
      and another one with a septicaemic Pseudomonas aeruginosa infection (44.1 ng/
      ml), ProCT values decreased rapidly under appropriate therapy. ProCT seems to be
      a specific marker of bacterial sepsis in HIV-infected patients, as no increase in
      other secondary infections could be detected in those patients. A rapid
      determination of ProCT level could be useful to confirm or refute bacterial
      sepsis for a better management of febrile HIV-infected patients.

PMID- 9279725
TI  - Recurrent bacterial meningitis: a 6-year experience in adult patients.
AB  - Ten adult patients with recurrent bacterial meningitis (RBM) of 22 episodes were
      diagnosed and treated at the Dicle University Hospital from January 1990 to
      December 1995. Apart from 22 episodes of RBM these patients had an additional 25
      episodes treated at other hospitals. The RBM attacks developed after closed head
      trauma in four patients, asplenia and chronic otitis media in one patient,
      chronic otitis media and oto-mastoiditis in one patient, chronic maxillary
      sinusitis in one patient, chronic mastoiditis in one patients, and suppurative
      foci of facial bones caused by shrapnel pieces and no predisposing condition in
      one patient. In 10 RBM episodes, Streptococcus pneumoniae was isolated from
      cerebrospinal fluid (CSF) and/or blood culture, and in one episode Proteus
      vulgaris was isolated from CSF and otitis media suppuration. In the four episodes
      both cultures were negative, but direct microscopy showed Gram-positive
      diplococci on Gram-staining. Three of the patients died from meningitis-related
      complications.

PMID- 9279726
TI  - The role of Blastocystis hominis as a possible intestinal pathogen in travellers.
AB  - The role of Blastocystis hominis as a pathogen for man has been controversially
      discussed, while travel history has been implicated as a risk factor of
      infection. Few controlled studies of the association between B. hominis and
      symptomatic diseases have been performed. Therefore, a case-control study among
      795 German tourists returning from tropical countries was conducted. The
      prevalence of the organism among patients with and without symptoms was assessed.
      Blastocystis hominis was detected in 69 of 469 (14.7%) patients with diarrhoea
      and in 21 of 326 (5.7%) controls. However, other organisms causing diarrhoea were
      detected in 18 of the 69 (26.1%) symptomatic patients with B. hominis. Thus, 51
      of 469 (10.8%) symptomatic patients had B. hominis in the absence of other
      pathogens in their stool, significantly more than in the asymptomatic group
      (5.2%; P = 0.005). Irrespective of the development of symptoms, the organism was
      most frequently acquired during journeys to the Indian subcontinent. The results
      of this study suggest that B. hominis is associated with development of diarrhoea
      in travellers to tropical destinations and that frequently concurrent infections
      with other organisms occur.

PMID- 9279727
TI  - Monitoring antiretroviral activity using ICDp24 and CD4 counts in HIV infection.
AB  - The fluctuations of HIV-1 p24 antigen concentration have been monitored in the
      follow-up of 118 subjects in different clinical stages and compared to their CD4
      cell count; 104 patients received antiretroviral therapy. Persistent (65%) or
      sporadic (28%) antigenaemia has been detected in most patients in different
      clinical stages. The variations of the p24 Ag level are significantly correlated
      with the CD4 cell count and therapy administration (P = 0.0001). In patients with
      relatively conserved immune function (CDC II and III), antiretroviral therapy
      shows the best efficacy and can be efficiently monitored by p24 and CD4 surrogate
      markers. The data here suggest that although the informative value of p24 Ag is
      not representative of an AIDS-defining event, it can be used as a short-term and
      relatively inexpensive virological marker of antiviral activity in vivo, to
      support the routine management of patients.

PMID- 9279728
TI  - Outpatient parenteral antimicrobial therapy: experience in a large teaching
      hospital.
AB  - OBJECTIVE: to determine the practicality of treatment of infectious conditions
      requiring prolonged parenteral antimicrobial therapy. METHOD: review of all
      patients admitted to a Regional Infectious Diseases (ID) Unit who received
      outpatient parenteral therapy over a 12-month period. The study identified the
      conditions suitable for outpatient therapy, the organization of treatment and the
      complications and financial implications of the service. RESULTS: fifteen
      patients (age range 32-81) received outpatient parenteral antimicrobial therapy
      during the period of the study. Five patients were HIV-positive and were treated
      for cytomegalovirus retinitis or severe recurrent candida infection with self
      administration of drugs through a Hickman line. HIV-negative patients were
      treated for osteomyelitis, deep-seated abscesses and subacute bacterial
      endocarditis. Eight of the 10 HIV-negative patients were given ceftriaxone once
      daily. The organization and delivery of outpatient drug therapy depended on the
      nature of the underlying infection and the availability of community services.
      Outpatient therapy was associated with considerable financial savings, and no
      serious adverse events were recorded. CONCLUSION: outpatient parenteral treatment
      is a reasonable option for a relatively small number of patients, representing
      less than 2% of patients admitted to the ID Unit over the time course of the
      study. Patients suitable for outpatient treatment have a stable medical condition
      and require prolonged antimicrobial therapy.

PMID- 9279729
TI  - Isolation of Enterococcus avium from bile and blood in a patient with acute
      cholecystitis.
AB  - The isolation of Enterococcus avium from bile fluid and blood of an uncompromised
      patient with acute cholecystitis is reported. As advanced identification of
      Enterococcus sp. by biochemical and physiological tests is not routinely done,
      the occurrence of E. avium infections may be underestimated.

PMID- 9279730
TI  - Cytomegalovirus encephalomyelomeningoradiculitis in acquired immunodeficiency
      syndrome (AIDS).
AB  - Acute inflammatory polyradiculitis represents an uncommon peripheral nerve
      complication during HIV infection. The case of an HIV-seropositive patient who
      was admitted to hospital for a cauda equina syndrome is reported. Despite early
      application of anticytomegalic medication, a cytomegalovrirus (CMV) infection
      spread out to the central nervous system (CNS), causing the patient's death. A
      post-mortem examination confirmed the diagnosis of CMV
      encephalomyelomeningoradiculitis. To the authors' knowledge, such a progress of a
      CMV-related polyradiculitis to an encephalomyelomeningoradiculitis has not yet
      been described. The clinical features of this case will aid in the recognition of
      CMV-related neurological complications, and may permit earlier and perhaps more
      successful treatment.

PMID- 9279731
TI  - A case of recurrent Candida parapsilosis prosthetic valve endocarditis: cure by
      medical treatment alone.
AB  - A patient with recurrent fungal endocarditis on prosthetic mitral valve is
      presented. Candida parapsilosis was the causative agent. The patient was treated
      medically with conventional amphotericin during the first episode. When the
      disease recurred conventional amphotericin B was used again, but had to be
      stopped because of severe side effects. Treatment was continued with amphotericin
      B colloidal dispersion, followed by fluconazole for 8 months. The patient is
      healthy 16 months after discontinuation of fluconazole. Medical treatment of
      fungal endocarditis on prosthetic valves can be successful in selected cases.

PMID- 9279732
TI  - Central nervous system involvement as a relapse of disseminated histoplasmosis in
      an Italian AIDS patient.
AB  - A case of an Italian AIDS patient who developed both meningitis and cerebral mass
      lesion as a final relapse of disseminated histoplasmosis is reported. Central
      nervous system (CNS) involvement occurred while the patient was receiving both
      amphotericin B and itraconazole as maintenance therapy, thus indicating the
      difficulty of eradicating histoplasmosis in patients with AIDS.

PMID- 9279733
TI  - Haemophilus segnis cholecystitis: a case report and literature review.
AB  - Haemophilus segnis is a normal commensal of the human oropharynx which is
      occasionally associated with appendicitis, endocarditis or pancreatic abscess.
      Haemophilus segnis in the gall-bladder from a 58-year-old white female was
      recently encountered. The patient recovered from surgery without incident. This
      case is reported because the gall-bladder is now another site which has become
      infected with this organism. In order to provide guidance to physicians when H.
      segnis organism is identified, microbiologists should be aware of its behaviour
      in different sites.

PMID- 9279734
TI  - Intracerebral sepsis due to intestinal perforation by ventriculo-peritoneal
      shunts: two cases.
AB  - Two cases of ventriculo-peritoneal (V-P) shunt infection attributable to
      intestinal perforation are reported. One patient developed a brain abscess, the
      other ventriculitis. Microbiology consisted of faecal flora and the peritoneal
      catheter was found to be faecally stained in both cases. There were no abdominal
      symptoms or signs. It is likely that infection developed via the ascending route.

PMID- 9279735
TI  - Paradoxical expansion of intracranial tuberculomas during chemotherapy.
AB  - A patient from India with military lung tuberculosis who developed intracranial
      tuberculomas under treatment with tuberculostatics is described. Computed
      tomography (CT) scans of the brain showed a progress of tuberculomas despite
      effective tuberculostatic therapy and adjunctive corticosteroid treatment. This
      phenomenon, termed 'paradoxical response' has rarely been reported. Continuation
      of chemotherapy led to improvement of brain lesions and a recovery of miliary
      tuberculosis. When intracranial tuberculomas develop, therapy should be continued
      for longer than is customary for uncomplicated tuberculosis infections. The use
      of steroids to suppress a 'paradoxical response' is not proven.

PMID- 9279736
TI  - Meningococcal meningitis with Arnold-Chiari malformation.

PMID- 9279737
TI  - Staphylococcus aureus meningitis--a rare complication of iliacus muscle abscess.
AB  - Staphylococcus aureus meningitis is a rare but well recognized condition which
      had a high mortality and incidence of neurological sequelae. It is usually
      associated with chronic underlying conditions. A case is reported of S. aureus
      meningitis in a previously healthy young man. The epidemiology, microbiological
      findings and treatment of this condition are discussed.

PMID- 9279738
TI  - Isospora belli in a patient with AIDS.

PMID- 9279739
TI  - Clinical ethics committees--pros and cons.

PMID- 9279740
TI  - Xenotransplantation.

PMID- 9279742
TI  - Patients' rights in England and the United States of America: The Patient's
      Charter and the New Jersey Patient Bill of Rights: a comparison.
AB  - The Patient's Charter has been in effect for nearly five years. This article
      considers the purpose and value of the document through a comparison with the New
      Jersey Patient Bill of Rights. Patient rights statements have been posted in
      American hospitals for more than twenty years. However, the New Jersey document
      and the patient rights programme it established seven years ago, have proven to
      be economically effective, successful in their representation of patients and
      enforceable, due to the adoption of state legislation and regulation to oversee
      the process. Several examples of how the programme works are included in the
      comparison, with a similar review of The Patient's Charter. In the comparison the
      author argues that for the programme to succeed as it has done in New Jersey, the
      government will need to develop legislative backing to ensure enforcement, and an
      efficient system for monitoring compliance. The programme will need to become
      credible in the eyes of the health service user. The author suggests this may be
      best achieved by developing an efficient, accessible and user-friendly means of
      redress, should the patient consider his or her rights have been violated. A
      "mish-mash" of quality assurance standards and levels of care which patients can
      "expect" from the health service providers only serves to distract the health
      service user from the government's failure to commit the resources that would
      empower the patients rights portion of The Patient's Charter.

PMID- 9279741
TI  - An analysis of CPR decision-making by elderly patients.
AB  - Traditionally clinicians have determined their patients' resuscitation status
      without consultation. This has been condemned as morally indefensible in cases
      where not for resuscitation (NFR) orders are based on quality of life
      considerations and when the patient's true wishes are not known. Such instances
      would encompass most resuscitation decisions in elderly patients. Having
      previously involved patients in CPR decision-making, we chose formally to explore
      the reasons behind the choices made. Although the patients were not upset, and
      readily decided at the time of initial consultation, on later analysing the
      decision-making we found poor understanding of the procedure, poor recall of
      information given and in some cases evidence of harm. This may be attributed to
      impaired decision-making capacity of elderly hospitalised patients as previously
      shown, or to the discomfort precipitated by having to contemplate the apparent
      immediacy of cardiac arrest by these patients. We propose that subscribing to
      autonomy as a general principle needs to be balanced against particular cases
      where distress may be caused by, or result in, diminished competence and limited
      autonomy.

PMID- 9279743
TI  - Existential autonomy: why patients should make their own choices.
AB  - Savulescu has recently introduced the "rational non-interventional paternalist"
      model of the patient-doctor relationship. This paper addresses objections to such
      a model from the perspective of an anaesthetist. Patients need to make their own
      decisions if they are to be fully autonomous. Rational non-interventional
      paternalism undermines the importance of patient choice and so threatens
      autonomy. Doctors should provide an evaluative judgment of the best medical
      course of action, but ought to restrict themselves to helping patients to make
      their own choices rather than making such choices for them.

PMID- 9279744
TI  - Partial and impartial ethical reasoning in health care professionals.
AB  - OBJECTIVES: To determine the relationship between ethical reasoning and gender
      and occupation among a group of male and female nurses and doctors. DESIGN:
      Partialist and impartialist forms of ethical reasoning were defined and singled
      out as being central to the difference between what is known as the "care" moral
      orientation (Gilligan) and the "justice" orientation (Kohlberg). A structured
      questionnaire based on four hypothetical moral dilemmas involving combinations of
      (health care) professional, non-professional, life-threatening and non-life
      threatening situations, was piloted and then mailed to a randomly selected sample
      of doctors and nurses. SETTING: 400 doctors from Victoria, and 200 doctors and
      400 nurses from New South Wales. RESULTS: 178 doctors and 122 nurses returned
      completed questionnaires. 115 doctors were male, 61 female; 50 nurses were male
      and 72 were female. It was hypothesised that there would be an association
      between feminine subjects and partialist reasoning and masculine subjects and
      impartialist reasoning. It was also hypothesised that nurses would adopt a
      partialist approach to reasoning and doctors an impartialist approach. No
      relationship between any of these variables was observed.

PMID- 9279745
TI  - Ethics and law in the field of medical care for the elderly in France.
AB  - The authors discuss law and ethics when medical decisions are to be taken by
      patients who are unable in any valid sense to express their own wishes. The main
      problem in legal terms is to protect an individual's free will as far as possible
      and ensure that his or her wishes, if known, are respected. If a patient's
      independent wishes cannot be known, then we must at least ensure that nothing is
      imposed which is not in his interest. Legal measures, however, are far from
      adequate in resolving all the concrete problems that emerge. The field of ethics
      does bring some better adapted solutions, but none is laid down in law. One such
      approach, involving a multidisciplinary advisory group in a department of
      geriatrics, is discussed.

PMID- 9279746
TI  - The new Italian code of medical ethics.
AB  - In June 1995, the Italian code of medical ethics was revised in order that its
      principles should reflect the ever-changing relationship between the medical
      profession and society and between physicians and patients. The updated code is
      also a response to new ethical problems created by scientific progress; the
      discussion of such problems often shows up a need for better understanding on the
      part of the medical profession itself. Medical deontology is defined as the
      discipline for the study of norms of conduct for the health care professions,
      including moral and legal norms as well as those pertaining more strictly to
      professional performance. The aim of deontology is therefore, the in-depth
      investigation and revision of the code of medical ethics. It is in the light of
      this conceptual definition that one should interpret a review of the different
      codes which have attempted, throughout the various periods of Italy's recent
      history, to adapt ethical norms to particular social and health care climates.

PMID- 9279748
TI  - The relationship between clinical audit and ethics.
AB  - The aim of this paper is to start a debate about ethical issues associated with
      the practice of clinical audit. This is an area that has not received much
      consideration. The role of clinical audit is to raise general clinical standards.
      The ethical issues of clinical audit may have far-reaching consequences for
      clinicians, patients, health care providers and purchasers. Guidance is required
      to provide consistency in approach so that those involved in clinical audit, at
      whatever level, can be confident that they are following good practice.
      Clinicians and managers often think of good practice as being a technical matter.
      The main point of this paper is to bring out important ethical dimensions to good
      practice.

PMID- 9279749
TI  - Medicine, the arts and imagination.

PMID- 9279747
TI  - Paediatrics at the cutting edge: do we need clinical ethics committees?
AB  - OBJECTIVES: To investigate the need for hospital clinical ethics committees by
      studying the frequency with which ethical dilemmas arose, the perceived adequacy
      of the process of their resolution, and the teaching and training of staff in
      medical ethics. DESIGN: Interviews with individuals and three multidisciplinary
      teams; questionnaire to randomly selected individuals. SETTING: Two major London
      children's hospitals. RESULTS: Ethical dilemmas arose frequently but were
      resolved in a relatively unstructured fashion. Ethical concerns included: the
      validity of consent for investigations and treatment; lack of children's
      involvement in consent; initiation of heroic or futile treatments; resource
      allocation. Staff expressed the need for a forum which would provide consultation
      on ethical issues, develop guidelines for good ethical practice, undertake
      teaching and training, and provide ethical reflection outside the acute clinical
      setting. CONCLUSION: Multidisciplinary, accountable and audited clinical ethics
      committees with predominantly advisory, practice development and educational
      roles could provide a valuable contribution to UK clinical practice and perhaps
      in other countries that have not developed hospital clinical ethics committees.

PMID- 9279750
TI  - Localisation of a gene causing endocrine neoplasia to a 4 cM region on chromosome
      1p35-p36.
AB  - The development of some endocrine tumours, such as medullary thyroid carcinomas,
      phaeochromocytomas, anterior pituitary adenomas, and parathyroid adenomas involve
      a putative tumour suppressor gene located on chromosome 1p32-pter, a region that
      represents 111 cM. In order to refine the location of this gene, 93 endocrine
      tumours (39 parathyroid adenomas, 40 anterior pituitary adenomas, seven
      pancreatic islet cell adenomas, and seven carcinoids) were investigated for loss
      of tumour heterozygosity (LOH) using the seven polymorphic loci 1pter-D1S228
      D1S507-D1S234-D1S476-D1S22 0-D1S207-D1S206-1cen. LOH was detected in 27% of the
      parathyroid tumours and in 7.5% of the pituitary tumours, but in none of the
      pancreatic islet cell or carcinoid tumours. In addition, seven of the 10
      parathyroid tumours that showed LOH of chromosome 1p facilitated a more precise
      mapping of this putative tumour suppressor gene; five tumours involved a loss
      only of the telomeric locus D1S228, whereas two other tumours showed LOH at the
      centromeric loci D1S507, D1S234, D1S476, and D1S220, but not D1S228. Thus, our
      results have mapped this tumour suppressor gene implicated in endocrine tumours
      to a 4 cM region flanked by D1S228 and D1S507 on chromosome 1p35-p36.

PMID- 9279751
TI  - RDS/peripherin gene mutations are frequent causes of central retinal dystrophies.
AB  - Patients from 76 independent families with various forms of mostly central
      retinal dystrophies were screened for mutations in the RDS/peripherin gene by
      means of SSCP analysis and direct DNA sequencing. Two nonsense mutations
      (Gln239ter, Tyr285ter), five missense mutations (Arg172Trp, Lys197Glu, Gly208Asp,
      Trp246Arg, Ser289Leu), and one single base insertion (Gly208insG), heterozygous
      in all cases, were detected. Only one of these mutations, Arg172Trp, has been
      reported previously. Cosegregation of the mutation with the disease phenotype
      could be established in selected families. Other missense mutations were excluded
      from a panel of 55-75 control subjects. The patients showed remarkable variation
      in phenotype and disease expression not only between cases with different
      mutations but also between affected members of the same family. This study
      indicates that RDS/peripherin mutations are a frequent cause of various types of
      central retinal dystrophies and that the RDS/peripherin gene exhibits a broad
      spectrum of allelic mutations. Comparative analysis of known mutations allowed us
      to hypothesise that the deleterious effect of RDS/peripherin gene mutations is
      the result of different molecular mechanisms.

PMID- 9279752
TI  - The effect of FMR1 CGG repeat interruptions on mutation frequency as measured by
      sperm typing.
AB  - Fragile X syndrome results from the unstable expansion of a CGG repeat within the
      FMR1 gene. Three classes of FMR1 alleles have been identified, normal alleles
      with 6-60 repeats, premutations with 60-200 repeats, and full mutations with >
      230 repeats. Premutations are exquisitely unstable upon transmission. Normal
      alleles, while generally stable upon transmission, are thought to have different
      intrinsic mutation frequencies, such that some normal alleles may be predisposed
      towards expansion while others may be more resistant to such change. One variable
      that may account for this difference is the occurrence of one or more AGG
      triplets punctuating the normal CGG repeat. The AGG interruptions lead to alleles
      that have equivalent overall length but different lengths of perfect repeats. To
      test the influence of the length of perfect repeats on stability, we examined the
      CGG repeat of single sorted sperm from two males, each with 39 total repeats, but
      distinct AGG interruption patterns. Sorted sperm of each donor showed -15%
      variation in repeat length, consistent with previous studies of sorted sperm at
      other triplet repeat loci. However, when discounting the majority variation of +/
      1 repeat, the male with 29 perfect repeats showed 3% expansion changes while the
      donor with only 19 perfect repeats had none (< 0.9%). Moreover, > 90% of all
      variant sperm, including all those observed with expansions, showed expansion or
      contraction of the 3' end of the repeat array. These data are consistent with the
      hypothesis that perfect repeat tracts influence the repeat stability and that
      changes of the FMR1 repeat exhibit polarity.

PMID- 9279754
TI  - Developmental enamel defects in tuberous sclerosis: a clinical genetic marker?
AB  - Ten probands with tuberous sclerosis (TS) and 20 first degree relatives were
      examined for evidence of pitted enamel hypoplasia; 100% of TS patients had
      pitting, compared to 65% of relatives and 72% of 25 controls. We found that 70%
      of TS cases had more than 14 pits per person compared with only 5% of relatives
      and 4% of controls; 85% of relatives and 84% of controls had fewer than six pits
      per person. Our results confirm that significantly increased numbers of dental
      enamel pits are found in persons with TS compared to controls. These results
      suggest that examination for the presence or absence of dental enamel pits is not
      a useful screening test for first degree relatives to detect otherwise
      unsuspected subjects with tuberous sclerosis. However, the lack of pits in first
      degree relatives in our study is probably largely because none of the relatives
      appeared to carry the TS gene.

PMID- 9279755
TI  - Cryptic terminal rearrangement of chromosome 22q13.32 detected by FISH in two
      unrelated patients.
AB  - Two unrelated patients with cryptic subtelomeric deletions of 22q13.3 were
      identified using FISH with the commercially available Oncor probe, D22S39.
      Proband 1 was found to have a derivative chromosome 22 resulting from the
      unbalanced segregation of a t(1;22)(q44;q13.32) in her mother. Additional FISH
      analysis of proband 1 and her mother placed the breakpoint on chromosome 22 in
      this family proximal to D22S55 and D22S39 and distal to D22S45. We have mapped
      D22S39 to within 170 kb of D22S21 using pulsed field gel electrophoresis. D22S21
      is genetically mapped between D22S55 and D22S45. These data indicate that the
      deletion in proband 1 is smaller than in eight of nine reported del(22)(q13.3)
      patients. Probands 1 and 2 share features of hypotonia, developmental delay, and
      expressive language delay, also seen in previously reported del(22)(q13.3)
      patients, although proband 1 appears to be more mildly affected. Proband 1 is
      also trisomic for the region 1q44-->qter. This very small duplication has been
      previously reported only once and the patient had idiopathic mental retardation.
      This is the first report where 22q13.3 terminal deletion patients have been
      identified through the use of FISH, and the first report of a deletion of this
      region occurring because of missegregation of a parental balanced cryptic
      translocation. We feel that investigation of the frequency of del(22)(q13.3) in
      the idiopathic mentally retarded population is warranted and may be aided by the
      ability to use a commercially available probe (D22S39), which is already
      currently in use in a large number of cytogenetic laboratories.

PMID- 9279753
TI  - Craniosynostosis associated with FGFR3 pro250arg mutation results in a range of
      clinical presentations including unisutural sporadic craniosynostosis.
AB  - Several mutations involving the fibroblast growth factor receptor (FGFR) gene
      family have been identified in association with phenotypically distinct forms of
      craniosynostosis. One such point mutation, resulting in the substitution of
      proline by arginine in a critical region of the linker region between the first
      and second immunoglobulin-like domains, is associated with highly specific
      phenotypic consequences in that mutation at this point in FGFR1 results in
      Pfeiffer syndrome and analogous mutation in FGFR2 results in Apert syndrome. We
      now show that a much more variable clinical presentation accompanies analogous
      mutation in the FGFR3 gene. Specifically, mental retardation, apparently
      unrelated to the management of the craniosynostosis, appears to be a variable
      clinical consequence of this FGFR3 mutation.

PMID- 9279756
TI  - De Lange syndrome: subjective and objective comparison of the classical and mild
      phenotypes.
AB  - Classical de Lange syndrome presents with a striking face, pronounced growth and
      mental retardation, and variable limb deficiencies. Over the past five years, a
      mild variant has been defined, with less significant psychomotor retardation,
      less marked pre- and postnatal growth deficiency, and an uncommon association
      with major malformations, although mild limb anomalies may be present. We have
      evaluated 43 subjects with de Lange syndrome, 30 with classical features, aged
      from birth to 21 years, and 13 with the mild phenotype, aged from 18 months to 30
      years. In addition to assessment of gestalt and facial change with time, detailed
      craniofacial measurements have been obtained on each subject and composite
      pattern profiles compiled. The characteristic face of classical de Lange syndrome
      is present at birth and changes little throughout life, although there is some
      lengthening of the face with age and the jaw becomes squared. In mild de Lange
      syndrome, the characteristic classical appearance may be present at birth, but in
      some subjects it may be two or three years before the typical face is obvious. In
      general, the overall impression is less striking, perhaps because of increased
      facial expression and greater alertness. With age, the face loses the
      characteristic appearance, the nasal height increases, the philtrum does not seem
      as long, and the upper vermilion is full and everted, although the crescent
      shaped mouth with downturned corners remains. Eyebrows may be full and bushy.
      Objective comparison of the face in mild and classical de Lange syndrome, through
      the use of craniofacial pattern profiles, shows marked similarity of patterns at
      4 to 9 years; both groups have microbrachycephaly, but the individual dimensions
      of the mild group are slightly closer to normal than their classical
      counterparts. The correlation coefficient is high (0.83). In the adult groups,
      similarity of patterns remains but is less marked. The normalisation of scores in
      the mild group is more dramatic. The correlation coefficient is lower (0.71).
      These objective findings substantiate clinical impressions of a phenotypic
      dichotomy. Early in life, the craniofacial features in mild de Lange syndrome may
      be indistinguishable from the classical phenotype and alternative discriminators
      must be sought in order to identify those subjects in whom the prognosis is more
      optimistic. Birth weight of more than 2500 g and absence of major limb anomalies
      may help in this regard.

PMID- 9279757
TI  - Counselling dilemmas associated with the molecular characterisation of two
      Angelman syndrome families.
AB  - We report the molecular characterisation of two families with Angelman syndrome
      referred for prenatal diagnosis, in which atypical molecular findings resulted in
      counselling dilemmas. The first is a familial case of Angelman syndrome in which
      the two affected children have mutations which affect the imprinting mechanism,
      as shown by the presence of paternal DNA methylation patterns at D15S63 and SNRPN
      and biparental inheritance of 15q11-q13 markers. DNA prepared from a 21 week
      fetal blood sample detected a fetus with normal maternal and paternal DNA
      methylation patterns at D15S63, but inheritance of the same maternal chromosome
      15q11-q13 as the two affected sibs. This is probably a result of germline
      mosaicism in the mother. The second is a case of Angelman syndrome with an
      atypical deletion of 15q11-q13, which involves both unusual proximal and distal
      breakpoints. The deletion was characterised in order to assess the risk of
      Angelman syndrome in a second pregnancy in the mother of this child.

PMID- 9279759
TI  - Neurogenic chronic idiopathic intestinal pseudo-obstruction, patent ductus
      arteriosus, and thrombocytopenia segregating as an X linked recessive disorder.
AB  - We present a family with three affected males in two generations with congenital
      neurogenic chronic idiopathic intestinal pseudo-obstruction (CIIP), patent ductus
      arteriosus, and large platelet thrombocytopenia apparently segregating as an X
      linked recessive disorder. The pattern of segregation of DNA markers within the
      family is consistent with linkage to the previously described neurogenic CIIP
      (CIIPX) locus at Xq28. This combination may represent a new contiguous gene
      disorder and appears to have a good prognosis with supportive therapy.

PMID- 9279760
TI  - Hydrocephalus and Hirschsprung's disease in a patient with a mutation of L1CAM.
AB  - Abnormalities of the L1CAM gene, a member of the immunoglobulin gene superfamily
      of neural cell adhesion molecules, are associated with X linked hydrocephalus and
      some allelic disorders. We describe a patient with X linked hydrocephalus and
      Hirschsprung's disease (HSCR) with a novel mutation in the L1CAM gene. This is
      the first report of HSCR with a mutant neural cell adhesion molecule. Although
      the disease phenotypes of this patient may well be independent, the alternative
      explanation that L1CAM mutations may contribute to both phenotypes cannot be
      excluded in view of an earlier report on another patient with both X linked
      hydrocephalus and HSCR.

PMID- 9279758
TI  - Waardenburg syndrome.
AB  - Auditory-pigmentary syndromes are caused by physical absence of melanocytes from
      the skin, hair, eyes, or the stria vascularis of the cochlea. Dominantly
      inherited examples with patchy depigmentation are usually labelled Waardenburg
      syndrome (WS). Type I WS, characterised by dystopia canthorum, is caused by loss
      of function mutations in the PAX3 gene. Type III WS (Klein-Waardenburg syndrome,
      with abnormalities of the arms) is an extreme presentation of type I; some but
      not all patients are homozygotes. Type IV WS (Shah-Waardenburg syndrome with
      Hirschsprung disease) can be caused by mutations in the genes for endothelin-3 or
      one of its receptors, EDNRB. Type II WS is a heterogeneous group, about 15% of
      whom are heterozygous for mutations in the MITF (microphthalmia associated
      transcription factor) gene. All these forms show marked variability even within
      families, and at present it is not possible to predict the severity, even when a
      mutation is detected. Characterising the genes is helping to unravel important
      developmental pathways in the neural crest and its derivatives.

PMID- 9279761
TI  - Assessment of French patients with LPL deficiency for French Canadian mutations.
AB  - Mutations in the LPL gene show high levels of allelic heterogeneity between and
      within different populations. Complete LPL deficiency has a very high prevalence
      in French Canadians, where only three missense mutations account for > 97% of
      cases, most consistent with founder mutations introduced early in Quebec by
      French immigrants. In order to determine whether these mutations were present in
      France, 12 unrelated French families with defined LPL deficiency were
      investigated for the presence of the mutations found in French Canadians. Of the
      24 expected alleles, six (25%) represented mutations in French Canadians
      (Gly188Glu four alleles, Asp250Asn and Pro207Leu one allele each). Comparison of
      French Canadian and French alleles identified the same haplotype in all carriers
      of the Gly188Glu and of the Asp250Asn, suggesting a common origin. In contrast,
      the Pro207Leu occurred on different haplotypes in France and Quebec, compatible
      with a different ancestral origin.

PMID- 9279762
TI  - "Cutis tricolor": congenital hyper- and hypopigmented macules associated with a
      sporadic multisystem birth defect: an unusual example of twin spotting?
AB  - An uncommon coexistence of circumscribed hyperpigmentation and hypopigmentation,
      in close proximity to each other, is described in a 17 years old patient with
      various other cogenital defects, such as dysmorphic facial appearance, severe
      kyphoscoliosis, delayed motor development, epileptic seizures, and mental
      retardation. We suggest the combination of hyper- and hypopigmented cutaneous
      lesions is an example of allelic twin spotting. Because the skin of this patient
      showed three different degrees of pigmentation the term "cutis tricolor" is
      proposed.

PMID- 9279763
TI  - Prenatal diagnosis of 22q11 deletions: a series of five cases with congenital
      heart defects.
AB  - We report a series of five patients with congenital heart defects in whom a
      prenatal diagnosis of 22q11 deletion has been made. The accurate cardiac and
      cytogenetic diagnoses were made between 20 and 23 weeks' gestation in all cases
      and the cardiac findings were all confirmed postnatally. The cardiac
      abnormalities included tetralogy of Fallot with absent pulmonary valve, pulmonary
      atresia with VSD, common arterial trunk, and left atrial isomerism with double
      outlet right ventricle. The problems of genetic counselling in these cases are
      discussed. A recommendation is made to test all fetuses with conotruncal heart
      abnormalities detected prenatally for a 22q11 deletion, whereas guidelines for
      other congenital heart disease types are less clear.

PMID- 9279764
TI  - Phenotypic expression of the fibroblast growth factor receptor 3 (FGFR3) mutation
      P250R in a large craniosynostosis family.
AB  - The craniosynostosis syndromes are a heterogeneous group of sporadic, autosomal
      dominant disorders with significant clinical overlap. Recently, we described a
      large family with autosomal dominant craniosynostosis suggestive of Saethre
      Chotzen syndrome, in which linkage to the Saethre-Chotzen syndrome loci on 7p had
      been excluded. We now report the presence of a mutation in the fibroblast growth
      factor receptor 3 (FGFR3) in this family. The mutation, P250R, had been
      previously reported in 10 patients with non-syndromic craniosynostosis. Variable
      expression of this mutation is evident especially in two additional members of
      this family, one of whom is severely affected with pancraniosynostosis. The
      family provides a further example of genetic heterogeneity and variable
      expression of the craniosynostosis syndromes and broadens the phenotypic spectrum
      associated with the FGFR3 mutation P250R. In addition, we found a polymorphism
      (F384L) in the transmembrane domain of FGFR3 which occurs with a frequency of 3%
      in the Turkish population but is uncommon among Germans.

PMID- 9279765
TI  - Genetic heterogeneity in Schwartz-Jampel syndrome: two families with neonatal
      Schwartz-Jampel syndrome do not map to human chromosome 1p34-p36.1.
AB  - Schwartz-Jampel syndrome (SJS) is a rare autosomal recessive disorder
      characterised by the presence of myotonia with a mask-like face, skeletal
      dysplasia, and growth retardation. Two types have been defined by the age of
      manifestation of the symptoms. Linkage of Schwartz-Jampel syndrome to human
      chromosome 1p34-p36.1 has been shown in families where probands presented during
      infancy or early childhood. We have investigated two well documented families
      segregating severe neonatal SJS with microsatellite markers spanning the critical
      region of 1p34-p36. No demonstrable linkage to chromosome 1 was found in either
      family, suggesting that a second locus is responsible for the severe form of
      neonatal Schwartz-Jampel syndrome.

PMID- 9279766
TI  - Monozygotic twins discordant for Aicardi syndrome.
AB  - Aicardi syndrome is a developmental disorder characterised by agenesis of the
      corpus callosum, retinal lacunae, seizures, and developmental delay. It is
      believed to be X linked with lethality in males. We report a set of monozygotic
      female twins one of whom is healthy and intellectually normal while the other has
      the classical Aicardi phenotype with profound retardation. Family history is
      negative. Both had normal karyotypes. Monozygosity was established by blood
      grouping, chromosomal heteromorphisms, and DNA analysis using six hypervariable
      probes (five autosomal and one X linked) and three X linked RFLP probes. We
      tested the hypothesis that preferential inactivation of a different X chromosome
      had occurred in each girl. Methylation sensitive RFLP analysis of DNA from EBV
      transformed B lymphocytes and cultured skin fibroblasts using MspI/HpaII
      digestion and probing with M27 beta showed a very similar pattern of X
      inactivation in both twins with no evidence of preferential expression of one
      particular X chromosome. We conclude that the abnormalities in the affected twin
      are probably the consequence of a postzygotic mutation in early embryonic
      development.

PMID- 9279767
TI  - Interstitial deletion, del(4)(q12q21.1), owing to de novo unbalanced
      translocation in a 2 year old girl: further evidence that the piebald trait maps
      to proximal 4q12.
AB  - A very short, microcephalic, and mentally retarded 2 year old girl showed minor
      anomalies including prominent occiput, delayed closure of the anterior
      fontanelle, high frontal hairline, prominent ears, upward slanting palpebral
      fissures, a small nose with bulbous tip, delayed tooth eruption and bone
      maturation, and short and tapering fingers and toes. She did not have a white
      forelock. Cytogenetic investigation disclosed a de novo unbalanced translocation
      between chromosomes 4 and 18 with deletion of 4q12-->q21.1. Molecular
      investigation showed lack of a paternal allele for the microsatellite markers
      D4S392 and D4S398. This case shows indirect evidence that the piebald gene maps
      to proximal 4q12.

PMID- 9279769
TI  - Juvenile onset Huntington's disease in an Omani child with asymptomatic, at risk
      parents.

PMID- 9279768
TI  - Familial four breakpoint complex chromosomal rearrangement as a cause of monosomy
      9p22-->pter and trisomy 10p11.2-->pter and 11q21 analysed by dual and triple
      colour FISH.
AB  - A familial four breakpoint complex chromosomal rearrangement involving
      chromosomes 9, 10, and 11 was ascertained through a child with dysmorphic
      features, hypertrophic cardiomyopathy, and hypotonia. A cryptic insertion,
      invisible in G banded chromosomes was identified by fluorescence in situ
      hybridisation (FISH) using chromosome specific libraries. Possible mechanisms of
      its formation as well as karyotype-phenotype correlation are discussed.

PMID- 9279770
TI  - Mirror hands and feet.

PMID- 9279771
TI  - A study of brothers with Klinefelter syndrome.

PMID- 9279772
TI  - Isoenzyme-specific cyclooxygenase inhibitors: a whole cell assay system using the
      human erythroleukemic cell line HEL and the human monocytic cell line Mono Mac 6.
AB  - NSAIDs inhibit the conversion of arachidonic acid into Prostaglandin G2 and
      Prostaglandin H2 which is catalyzed by the enzyme cyclooxygenase (COX). Two
      genetically distinct isoforms have been discovered, COX-1 and COX-2. While COX-1
      is thought to account for homeostatic amounts of eicosanoids, COX-2 is induced
      during inflammation leading to pathologic amounts of eicosanoids. Since NSAIDs
      inhibit both COX isoforms, antiinflammatory drug research has refocused to
      discovering COX-2 inhibitors that do not inhibit COX-1. For this purpose, we have
      developed a whole cell assay system using the human erythroleukemic cell line HEL
      as a source for COX-1 and the human monocytic cell line Mono Mac 6 as a source
      for COX-2. Mono Mac 6 cells express high amounts of COX-2 upon stimulation with
      lipopolysaccharide (LPS) in the absence of any detectable COX-1 protein. On the
      other hand, we find HEL cells to naturally express COX-1 protein, but not COX-2.
      Testing of a panel of NSAIDs as well as some COX-2 specific inhibitors showed
      that this assay system is suitable for identifying compounds that selectively
      inhibit either COX-1 or COX-2. This test system offers the advantage of assessing
      COX-1 and COX-2 inhibitors within the human species, within a similar test set
      up, and circumvents the need for tedious purification of either platelets or
      peripheral blood monocytes.

PMID- 9279773
TI  - How to express an effect mean as percentage of a control mean?
AB  - The expression of effects as % of corresponding controls requires to consider the
      variance of these controls. Fieller's Theorem allows the appropriate calculation
      of the deviation of % values. The Zero-Method, which wrongly assumes that the
      variance of controls is zero, may lead to doubtful interpretations, as shown with
      experimental examples on the inhibition of depolarization-evoked transmitter
      release.

PMID- 9279774
TI  - Study of the distribution of albendazole-sulphoxide (ABZ-SO) in fertilized egg
      compartments.
AB  - In order to use the chicken embryo in teratogenic studies, it is necessary to
      know the internal volume in which a xenobiotic distributes. The inoculation of a
      xenobiotic in one of the compartments of the fertilized egg is the usual
      technique used in these studies. Neither the concentration nor the moment in
      which the xenobiotic comes into contact with the chicken embryo have been
      considered. Predicting the internal volume of distribution in the egg from some
      of the external parameters that do not interfere with the normal development is
      necessary. A simple method to calibrate these external parameters and their
      correlation with the different compartments of the fertilized eggs as well as the
      different distribution of the xenobiotic in these compartments has been
      successfully demonstrated. After injection of ABZ-SO, the maximum concentration
      in the embryo is reached by 36 h. The mean AUC for the albumen (sharp and obtuse
      end), yolk, and embryo were 78.4, 40.7, 79.2, and 10.8 micrograms.h/ml
      respectively. The results obtained about the kinetics of the diffusion of ABZ-SO
      indicate that this compound does not have a homogeneous distribution in all the
      compartments of the fertilized egg. These results highlight that whenever
      fertilized eggs are used as a screening for the possible toxicity of a drug or
      other substances, the dose of the xenobiotic to be injected has to be precisely
      determined in accordance with the total volume and the stage of embryonic
      development selected to be affected, starting from the previous knowledge of when
      and how much substance accedes to the embryo.

PMID- 9279775
TI  - Renal function in the noninsulin-dependent diabetic rat: effects of unilateral
      nephrectomy.
AB  - A new model of noninsulin-dependent diabetic (NIDD) is described which exhibits
      more prominent defects in renal function than does the standard neonatal NIDD
      model. To produce this model, 2-day-old neonatal male Wistar Kyoto (WKY) rats
      were injected intraperitoneally with streptozotocin (90 mg/kg; NIDD), while their
      corresponding nondiabetic controls were administered vehicle (citrate buffer, pH:
      4.5; control). At 3 weeks of age, the animals were weaned, and 1 week later,
      under ether anesthesia, the animals underwent a right nephrectomy or a sham
      operation. Diabetes was confirmed by intraperitoneal administration of a glucose
      load (2g/kg), which resulted in significantly higher blood glucose concentration
      in the NIDD, compared to the nondiabetic rats. Surgical reduction of renal mass
      had no effect on the glycemic response to a glucose tolerance test in either
      group. Intravenous administration of an isotonic saline load resulted in a
      similar pattern of enhanced sodium and fluid excretion in the two-kidney sham
      operated nondiabetic and NIDD rats. These responses were significantly higher
      than those observed in their counterparts with one remaining kidney. Yet, the
      natriuretic and diuretic responses to the saline load were significantly lower in
      the nephrectomized NIDD, compared to the nephrectomized nondiabetic rats. The
      glomerular filtration rate was similar in the sham-operated (two kidneys) NIDD
      and nondiabetic rats. In contrast, both the basal and saline-stimulated
      glomerular filtration rate were lower in the nephrectomized NIDD rats compared to
      the nephrectomized nondiabetic group. Mean arterial pressure was similar between
      the two nephrectomized groups, thereby ruling out a significant contribution from
      the pressure-diuresis-natriuresis mechanism to the reduction in sodium and fluid
      excretion in the nephrectomized NIDD rats. Thus, unilateral nephrectomy is an
      effective method of accelerating the manifestation of NIDD-related renal
      alterations. The mild, but progressive, nature of diabetes in this model should
      facilitate the investigation of temporal changes in renal function in NIDDM.

PMID- 9279776
TI  - Positive inotropic effect of angiotensin II. Increases in intracellular Ca2+ or
      changes in myofilament Ca2+ responsiveness?
AB  - Although it is well known that Angiotensin II (Ang II) has a direct positive
      inotropic effect in several species, the mechanisms of this action are still
      poorly understood. The aim of this review is to analyze the possible subcellular
      mechanisms underlying Ang II-induced positive inotropic action. The binding of
      Ang II to its receptor triggers a complex signal transduction cascade that
      stimulates the intracellular formation of two second messengers, inositol 1,4,5
      triphosphate (IP3), and 1,2, diacylglycerol (DAG). IP3 triggers the release of
      Ca2+ from intracellular stores in several cell types and has been shown to
      increase myofilament Ca2+ sensitivity. DAG activates protein kinase C (PKC), an
      enzyme that catalyzes the phosphorylation of different cellular proteins,
      including several proteins of the myofibrils. Distinct ionic transporters, like
      the Na+/H+ antiporter and the Na(+)-independent Cl-/HCO3- exchanger, implicated
      in the regulation of intracellular pH, and the Na+/Ca2+ exchanger which
      contribute to the intracellular Ca2+ homeostasis, have been shown to be activated
      by a PKC-dependent mechanism. Thus, either one of the Ang II-induced second
      messengers, that is, IP3 and DAG, has the potential to affect myocardial
      contractility by modifying either intracellular Ca2+, myofilament Ca2+
      responsiveness, or both. As described herein, the available data do not allow a
      definitive single model to explain the mechanism of the Ang II-induced positive
      inotropic effect. Moreover, it is possible that the final action of Ang II on
      myocardial inotropism is the end product of a complex interaction of several of
      the mechanisms triggered by the hormone.

PMID- 9279778
TI  - Combination of antisense oligonucleotide and low-dose chemotherapy in
      hematological malignancies.
AB  - Current conventional chemotherapy for the treatment of hematological
      malignancies, although quite effective, has associated toxicities to normal
      tissue and organs, which is still a major dose limiting factor. In addition, high
      dose chemotherapy followed by autologous stem cell transplantation is limited by
      tumor cell contamination in the stem cell harvest. The use of conventional
      chemotherapy alone to purge these tumor cell contaminants is known to damage
      normal hematopoietic progenitor cells, resulting in delayed engraftment. The
      combination of antisense oligodeoxynucleotides (ODN) and low doses of
      chemotherapy offer a potential regiment which may lower the doses of conventional
      therapeutics required to effectively combat disease, thus lowering cytotoxicity
      experienced by normal cells. Transient downregulation of genes by ODN treatment,
      which are involved in the transformation or perpetuation of the cancerous disease
      state, can remove the growth and survival advantages exploited by tumor cells.
      Many groups are currently investigating this combination and have produced
      intriguing results. This review article discusses the current research
      investigating the combination of antisense ODN therapy with conventional
      chemotherapy in the treatment of hematological malignancies. Although further
      improvements in this strategy are required, the results thus far support a future
      for this strategy in clinical management of hematological malignancy.

PMID- 9279777
TI  - Morphological and biochemical characterization and analysis of apoptosis.
AB  - Apoptosis is a form of programmed cell death serving physiologic and homeostatic
      functions. However, recent evidence implicating apoptosis in the etiology and
      pathophysiology of known human diseases, such as heart diseases, cancer, AIDS,
      and neurodegenerative and autoimmune diseases are continually surfacing. This has
      spawned the need for identifying which methods are the most effective and well
      accepted to decipher its presence in a variety of research settings. We have
      therefore detailed the morphology and biochemical features of apoptotic cell
      death, with an emphasis on discriminating it from necrosis. In addition, we
      describe specific and selective techniques which are optimal to target hallmark
      apoptotic features, such as microscopy, Annexin V labeling, in situ nick-end
      labeling (TUNEL), and DNA fragmentation analysis by gel electrophoresis and ELISA
      for oligonucleosome-sized DNA. The advantages and disadvantages of each technique
      are discussed, as well as their experimental importance relative to one another.
      The methods have been described in a stepwise fashion, and can readily be applied
      in the majority of cell systems. Whether working on the tissue or single cell
      level, these methods are highly effective in qualifying and quantifying
      apoptosis. The application of these methods in conjunction with molecular
      techniques can further delineate the underlying mechanisms of apoptosis.

PMID- 9279779
TI  - Direct detection of the internal acyl migration reactions of benzoic acid 1-O
      acylglucuronide by 13C-labeling and nuclear magnetic resonance spectroscopy.
AB  - 1-O-Acyl-beta-D-glucopyranuronates can undergo irreversible binding to proteins
      mainly through internal acyl migration reactions, which may have toxicological
      significance. A new method based on the 13C-labeling and nuclear magnetic
      resonance (NMR) spectroscopy has been developed to study the reactivity of the 1
      O-acyl-beta-D-glucopyranuronate of benzoic acid. In phosphate buffer (pH 7.4)
      solution at 37 degrees C, the glucuronide showed apparent first-order degradation
      kinetics (T1/2, 125 min), and concurrent and sequential appearance of 2-, 3- and
      4-O-acyl isomers as both alpha- and beta-anomers was observed. The isomeric
      glucuronides were identified by two-dimensional NMR of the reaction mixture. The
      direct approach using 13C-labeling and NMR could also provide insights into the
      reactivities of other labile drug acylglucuronides and their isomeric
      glucuronides.

PMID- 9279800
TI  - Coming closer: structure and function of calcium-activated K+ channels in
      coronary arteries.

PMID- 9279801
TI  - The effect of tetracaine on spontaneous Ca2+ release and sarcoplasmic reticulum
      calcium content in rat ventricular myocytes.
AB  - 1. The effects of tetracaine were studied on voltage-clamped rat ventricular
      myocytes, which exhibited Ca2+ overload as identified by spontaneous Ca2+ release
      from the sarcoplasmic reticulum (SR) as shown by the associated contractions.
      This Ca2+ release was initially abolished by tetracaine before returning at a
      lower frequency, but greater amplitude, than the control. On removal of
      tetracaine, there was a burst of spontaneous Ca2+ release activity. All these
      effects were dose dependent, from 25 to 200 microM tetracaine. 2. The spontaneous
      Ca2+ release activated an inward Na(+)-Ca2+ exchange current as Ca2+ was pumped
      out of the cell. The integral of this current (i.e. the Ca2+ efflux) was
      increased in the presence of tetracaine. The calcium efflux per unit time was
      unaffected by tetracaine. 3. The SR Ca2+ content was increased by tetracaine, as
      shown by the integral of the caffeine-evoked Na(+)-Ca2+ exchange current. The
      increase of SR Ca2+ content was equal to the extra Ca2+ lost from the cell during
      the burst on removal of tetracaine, and to estimates of the extra calcium gained
      over the quiescent period following addition of tetracaine. 4. It is concluded
      that partial inhibition of calcium-induced calcium release increases SR Ca2+
      content. In the steady state, cell Ca2+ balance is maintained as the lower
      frequency of spontaneous release (that activates efflux) is compensated for by
      their greater size.

PMID- 9279802
TI  - Drastic facilitation by alpha-latrotoxin of bovine chromaffin cell exocytosis
      without measurable enhancement of Ca2+ entry or [Ca2+]i.
AB  - 1. Latrotoxin (LTX, 1-3 nM) caused a gradual increase of the spontaneous
      catecholamine release rate in bovine adrenal chromaffin cells superfused with
      normal Krebs-Hepes solution containing 2.5 mM Ca2+. Ca2+ removal abolished this
      effect. LTX enhanced also the secretory responses to high K+ (35 or 70 mM) and to
      acetylcholine (ACh, 30 microM). 2. The application of Ca2+ pulses to cells
      previously superfused with a 0 Ca2+ solution (Krebs-Hepes deprived of CaCl2)
      induced secretory responses that gradually reached 400-800 nA of catecholamines,
      provided that LTX was present. The responses to ACh or 35 mM K+ pulses (in the
      presence of Ca2+) were also enhanced by LTX, from around 100-200 nA to over 1000
      nA. Though such enhancement remained in the presence of Ca2+ channel blockers, it
      disappeared upon the lowering of [Na+]o or in electroporated cells. 3. Using
      protocols similar to those of secretion, LTX did not enhance basal 45Ca2+ uptake,
      whole-cell Ca2+ currents or basal [Ca2+]i. In fact, LTX attenuated the K(+)- or
      ACh-evoked increases in 45Ca2+ uptake and [Ca2+]i. 4. It is proposed that the
      secretory response to brief periods of Ca2+ reintroductions is triggered by local
      subplasmalemmal Ca2+i transients, produced by the Na(+)-Ca2+ exchanger of the
      plasma membrane working in the reverse mode. This situation might be
      physiologically reproduced during ACh stimulation of chromaffin cells, which is
      followed by the firing of Na(+)-dependent action potentials.

PMID- 9279803
TI  - Activation of small conductance Ca(2+)-dependent K+ channels by purinergic
      agonists in smooth muscle cells of the mouse ileum.
AB  - 1. Whole-cell and single-channel K+ currents were recorded at room temperature
      (22-24 degrees C), from smooth muscle cells enzymatically dispersed from the
      mouse ileum, using variations of the patch-clamp technique. 2. Net outward K+
      currents recorded through amphotericin-B-perforated patches in response to step
      depolarizations positive to -50 mV from a holding potential of -80 mV were
      decreased by up to 70% by external apamin (0.5 microM). Apamin-sensitive whole
      cell currents were also recorded from cells perfused internally with 150 nM Ca2+
      but not from cells perfused internally with 85 nM Ca2+. 3. Three types of non
      inactivating Ca(2+)-sensitive K+ channels were identified in cell-attached and
      excised patches under an asymmetrical K+ gradient: (i) large conductance (BKCa;
      approximately 200 pS) channels blocked by 2 mM external TEA; (ii) intermediate
      conductance (IKCa; approximately 39 pS) channels blocked by 2 mM external TEA and
      inhibited by external apamin (0.5 microM); and (iii) small conductance (SKCa;
      approximately 10 pS) channels that were not blocked by 5 mM external TEA but were
      sensitive to extracellular apamin (0.5 microM). 4. The TEA-resistant SKCa
      channels were activated by an increase in [Ca2+]i with an EC50 of 1.5 microM and
      a Hill coefficient of 1.3. 5. P2 purinoceptor agonists 2-methylthioATP (2
      MeSATP), 2-chloroATP and ATP (10-50 microM) increased an apamin-sensitive whole
      cell outward K+ current. Extrapatch application of 2-MeSATP (20-100 microM)
      stimulated the apamin-sensitive IKCa and SKCa channels and activated an apamin
      sensitive steady outward current at 0 mV. 6. Smooth muscle cells from the mouse
      ileum possess two apamin-sensitive K+ channels (IKCa and SKCa); of these, the
      IKCa channels are TEA sensitive while the SKCa channels are TEA resistant. These
      channels, along with an apamin-sensitive but TEA-resistant steady outward
      current, may mediate membrane hyperpolarization elicited by purinergic agonists.

PMID- 9279804
TI  - Spatial heterogeneity of intracellular Ca2+ signals in axons of basket cells from
      rat cerebellar slices.
AB  - 1. Using tight-seal whole-cell recording and digital fluorescence imaging, we
      studied intracellular calcium (Ca2+i) dynamics in cerebellar basket cells, whose
      dendrites, axon and presynaptic terminals are coplanar, an optimal configuration
      for simultaneous optical measurements of all functional domains. 2. In Cs(+)
      loaded neurones, depolarizing pulses induced large Ca2+i transients in single
      axonal varicosities and synaptic terminals, contrasting with much weaker signals
      between varicosities or in the somato-dendritic domain. 3. Axonal branch points
      consistently displayed [Ca2+]i rises of similar magnitude and time course to
      those in axonal terminals and varicosities. 4. In biocytin-filled basket cells,
      varicosity-like swellings were present along the axon including its branch
      points. Thus, axonal enlargements are not due to fluorescence-induced cell
      damage. 5. The spatial heterogeneity of Ca2+i signals was also observed in K(+)
      loaded cells upon depolarizing trains, suggesting that this behaviour is an
      intrinsic property of Ca2+i homeostasis in basket cells. 6. We conclude that
      depolarization of basket cell axons evokes high local Ca2+i signals in synaptic
      terminals, en passant varicosities and branch points. While high [Ca2+]i in
      presynaptic structures presumably triggers transmitter release, Ca2+i transients
      at branch points may control signal transmission in the axonal arborization.

PMID- 9279805
TI  - Calcium in sympathetic varicosities of mouse vas deferens during facilitation,
      augmentation and autoinhibition.
AB  - 1. The sympathetic nerve terminals of the mouse vas deferens were loaded with the
      calcium indicator Oregon Green 488 BAPTA-1 by orthograde transport along the
      postganglionic nerves. Changes in the calcium concentration in the varicosity
      (delta [Ca2+]v) were determined following single impulses, and short (5-impulse)
      and long (200-impulse) trains at 5 Hz. 2. All varicosities showed a significant
      delta [Ca2+]v in response to every single impulse. The elevated delta [Ca2+]v
      declined in two phases with similar kinetics for all varicosities: a fast phase
      (time constant, 0.42 +/- 0.05 s) and a moderate phase (3.6 +/- 0.4 s). 3. Line
      scanning confocal microscopy revealed that the delta [Ca2+] of a single terminal
      following single impulses was smaller for the intervaricose regions than for the
      varicosities. 4. Blockade of the voltage-sensitive calcium channels with Cd2+ (in
      calcium-free solution) completely blocked the delta [Ca2+]v on stimulation. The
      addition of either nifedipine (10 microM), omega-conotoxin GVIA (100 nM) or omega
      agatoxin TK (100 nM) showed that 47 +/- 6% of the evoked response was mediated by
      N-type calcium channels. 5. Ryanodine (10 microM) did not significantly change
      the amplitude of delta [Ca2+]v in response to short trains. 6. Spontaneous
      increases in delta [Ca2+]v were observed in individual varicosities, with
      coupling in the increase of delta [Ca2+]v between varicosities. 7. The
      presynaptic alpha 2-receptor antagonist yohimbine (10 microM) increased the
      amplitude of delta [Ca2+]v in response to five impulses (5 Hz) by 54 +/- 14%,
      while the alpha 2-receptor agonist clonidine (1 microM) decreased the delta
      [Ca2+]v by 55 +/- 4%. 8. These results are discussed in terms of the hypotheses
      that the increased probability for secretion at sympathetic nerve terminals which
      accompanies facilitation and augmentation is due to the residual delta [Ca2+]v
      remaining after the calcium influx following impulses and that noradrenaline acts
      presynaptically to decrease the probability of secretion by modifying calcium
      influx.

PMID- 9279806
TI  - Amino terminal-dependent gating of the potassium channel rat eag is compensated
      by a mutation in the S4 segment.
AB  - 1. Rat eag potassium channels (r-eag) were expressed in Xenopus oocytes. They
      gave rise to delayed rectifying K+ currents with a strong Cole-Moore effect. 2.
      Deletions in the N-terminal structure of r-eag either shifted the activation
      threshold to more negative potentials and slowed the activation kinetics (delta 2
      190, delta 2-12 and delta 7-12) or resulted in a shift to more positive
      potentials and faster activation kinetics (delta 150-162). 3. The impact of the
      deletion delta 7-12 was investigated in more detail: it almost abolished the Cole
      Moore effect and markedly slowed down channel deactivation. 4. Unlike wild-type
      channels, the deletion mutants delta 7-12 exhibited a rapid inactivation which,
      in combination with the slow deactivation, resulted in current characteristics
      which were similar to those of the related potassium channel HERG. 5. Both the
      slowing of deactivation and the inactivation induced by the deletion delta 7-12
      were compensated by a single histidine-to-arginine change in the S4 segment,
      while this mutation (H343R) only had minor effects on the gating kinetics of the
      full-length r-eag channel. 6. These results demonstrate a functional role of the
      N-terminus in the voltage-dependent gating of potassium channels which is
      presumably mediated by an interaction of the N-terminal protein structure with
      the S4 motif during the gating process.

PMID- 9279807
TI  - Molecular constituents of maxi KCa channels in human coronary smooth muscle:
      predominant alpha + beta subunit complexes.
AB  - 1. Human large-conductance voltage- and calcium-sensitive K+ (maxi KCa) channels
      are composed of at least two subunits: the pore-forming subunit, alpha, and a
      modulatory subunit, beta. Expression of the beta subunit induces dramatic changes
      in alpha subunit function. It increases the apparent Ca2+ sensitivity and it
      allows dehydrosoyasaponin I (DHS-I) to upregulate the channel. 2. The functional
      coupling of maxi KCa channel alpha and beta subunits in freshly dissociated human
      coronary smooth muscle cells was assessed. To distinguish maxi KCa currents
      modulated by the beta subunit, we examined (a) their apparent Ca2+ sensitivity,
      as judged from the voltage necessary to half-activate the channel (V1/2), and (b)
      their activation by DHS-I. 3. In patches with unitary currents, the majority of
      channels were half-activated near -85 mV at 18 microM Ca2+, a value similar to
      that obtained when the human KCa channel alpha (HSLO) and beta (HKV,Ca beta)
      subunits are co-expressed. A small number of channels half-activated around 0 mV,
      suggesting the activity of the alpha subunit alone. 4. The properties of
      macroscopic currents were consistent with the view that most pore-forming alpha
      subunits were coupled to beta subunits, since the majority of currents had values
      for V1/2 near to -90 mV, and currents were potentiated by DHS-I. 5. We conclude
      that in human coronary artery smooth muscle cells, most maxi KCa channels are
      composed of alpha and beta subunits. The higher Ca2+ sensitivity of maxi KCa
      channels, resulting from their coupling to beta subunits, suggests an important
      role of this channel in regulating coronary tone. Their massive activation by
      micromolar Ca2+ concentrations may lead to a large hyperpolarization causing
      profound changes in coronary blood flow and cardiac function.

PMID- 9279808
TI  - Different G proteins mediate somatostatin-induced inward rectifier K+ currents in
      murine brain and endocrine cells.
AB  - 1. Types of G proteins (G protein alpha-subunit subtypes) which mediate the
      activation of inward rectifier K+ currents by somatostatin (somatotrophin release
      inhibiting factor, SRIF) were determined in cultured locus coeruleus neurones
      from newborn rats and in AtT-20 cells (a mouse pituitary cell line). 2. The whole
      cell patch clamp technique was used together with injection of antibodies against
      pertussis toxin (PTX)-sensitive G protein alpha-subunits or with injection of
      antisense (or sense) oligonucleotides against these G proteins. 3. In locus
      coeruleus neurones, the SRIF-induced activation of inward rectifier K+ currents
      was inhibited by anti-G alpha i1/G alpha i2 antibody injection, but not by anti-G
      alpha i3 or by anti-G alpha o/G alpha i3 antibody injection, suggesting that the
      SRIF response is mediated through G alpha i1 and/or G alpha i2. 4. The SRIF
      induced activation of the inward rectifier was suppressed in locus coeruleus
      neurones after injection of antisense oligonucleotides against G alpha i2, but
      not by injection of sense oligonucleotides against G alpha i2. Injection of
      antisense (or sense) oligonucleotides against G alpha i1, G alpha i3 and G alpha
      O (common) had no effect. These results suggest that G alpha i2 is involved in
      this SRIF response. 5. In AtT-20 cells, the SRIF-induced activation of inward
      rectifier K+ currents was suppressed by injection of anti-G alpha i3 antibody,
      but not by injection of anti-G alpha i1/G alpha i2 antibody. 6. The above results
      indicate that Gi mediates the SRIF effects on inward rectifier K+ currents.
      However, different subtypes of Gi are involved in the brain neurones and in the
      endocrine cells: Gi2 in locus coeruleus neurones and Gi3 in AtT-20 cells.

PMID- 9279809
TI  - Calcium dependence and distribution of calcium-activated chloride channels in
      Xenopus oocytes.
AB  - 1. The Ca(2+)-dependent Cl- current (ICl,Ca), expressed in the plasma membrane of
      Xenopus oocytes, was examined in excised inside-out macropatches using a rapid
      perfusion system. 2. Application of Ca(2+)-containing Ringer solution resulted in
      the activation of a current whose reversal potential shifted to the right by 51
      +/- 5.2 mV when Cl- in the pipette solution was lowered from 119.3 to 10 mM. No
      currents were generated when Ca2+ was omitted from the solution. The current is
      therefore a Ca(2+)-activated Cl- one. 3. Following exposure to Ca2+, the half
      time for activation of ICl,Ca was not voltage dependent, whereas deactivation was
      strongly so. 4. ICl,Ca was stable in the continuous presence of Ca2+ and showed
      no sign of inactivation or adaptation. 5. Comparison of the size of the currents
      (normalized to pipette resistance) from the animal and vegetal poles revealed
      that ICl,Ca had a highly polarized distribution. The current density was almost
      10 times higher in the animal pole. 6. The results suggest that Cl- channels
      provide a continuous and reliable indication of submembranous Ca2+, at least in
      an excised patch, and the clustering of the Cl- channels renders it necessary to
      exert caution in interpreting results involving the kinetics of Ca2+ signalling,
      when ICl,Ca is used as the sole monitor of calcium.

PMID- 9279811
TI  - Spatiotemporal patterns of gamma frequency oscillations tetanically induced in
      the rat hippocampal slice.
AB  - 1. We used transverse and longitudinal rat hippocampal slices to study the
      synchronization of gamma frequency (> 20 Hz) oscillations, across distances of up
      to 4.5 mm. gamma oscillations were evoked in the CA1 region by tetanic
      stimulation at one or two sites simultaneously, and were associated with
      population spikes. Tetanic stimuli that were strong enough to induce oscillations
      were associated with depolarization of both pyramidal cells and interneurones,
      largely produced by activation of metabotropic glutamate receptors. 2. Computer
      simulations of gamma oscillations were also performed in a model with pyramidal
      cells and interneurones, arranged in a chain of five cell groups. This model had
      suggested previously that interneurone networks alone could generate synchronous
      gamma oscillations locally, but that pyramidal cell firing, by inducing spike
      doublets in interneurones, was necessary for the occurrence of highly correlated
      oscillations with small phase lag (< 2.5 ms), in a distributed network possessing
      long axon conduction delays. 3. In both experiment and model, pyramidal cell
      spikes occurred in phase with local population spikes, as did the first spike of
      the interneurone doublet. 4. The conductance of the interneurone alpha-amino-3
      hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-mediated conductance
      was manipulated in the model, while the relation between oscillations at opposite
      ends of the chain was examined. When the conductance was large enough for doublet
      firing to be synaptically induced in interneurones, oscillation phase lags were <
      2.25 ms across the chain. As predicted, experimental blockade of AMPA receptors
      resulted in increased phase lags between two sites oscillating simultaneously,
      compared with control conditions. 5. Both in model and in experiment, when
      stimuli to the two ends of the network were slightly different, cross-network
      synchronization occurred with a shorter phase lag at high frequencies than at
      lower frequencies. 6. These data suggest that, while interneurone networks alone
      can generate locally synchronized gamma oscillations, firing of pyramidal cells,
      and the synaptically induced doublet firing in interneurones, contribute to the
      stability and tight synchrony of the oscillations in distributed networks.

PMID- 9279810
TI  - Permeation and block of rat GluR6 glutamate receptor channels by internal and
      external polyamines.
AB  - 1. Polyamine block of rat GluR6(Q) glutamate receptor channels was studied in
      outside-out patches from transiently transfected HEK 293 cells. With symmetrical
      150 mM Na+ and 30 microM internal spermine there was biphasic voltage dependence
      with 95% block at +40 mV but only 20% block at +140 mV. Dose-inhibition analysis
      for external spermine also revealed biphasic block; the Kd at +40 mV (54 microM)
      was lower than at +80 (167 microM) and -80 mV (78 microM). 2. For internal
      polyamines relief from block was most pronounced for spermine, weaker for N-(4
      hydroxyphenylpropanoyl)-spermine (PPS), and virtually absent for philanthotoxin
      343 (PhTX 343), suggesting that permeation of polyamines varies with cross
      sectional width (spermine, 0.44 nm; PPS, 0.70 nm; PhTX 343, 0.75 nm). 3. With
      putrescine, spermidine, or spermine as sole external cations, inward currents at 
      120 mV confirmed permeation of polyamines. For bi-ionic conditions with 90 mM
      polyamine and 150 mM Na+i, reversal potentials were -12.4 mV for putrescine
      (permeability ratio relative to Na+, PPut/PNa = 0.42) and -32.7 mV for spermidine
      (PSpd/PNa = 0.07). Currents carried by spermine were too small to analyse
      accurately in the majority of patches. 4. Increasing [Na+]i from 44 to 330 mM had
      no effect on the potential for 50% block (V1/2) by 30 microM internal spermine;
      however, relief from block at positive membrane potentials increased with [Na+]i.
      In contrast, raising [Na+]o from 44 to 330 mM resulted in a depolarizing shift in
      V1/2, indicating a strong interaction between internal polyamines and external
      permeant ions. 5. The Woodhull infinite barrier model of ion channel block
      adequately described the action of spermine at membrane potentials insufficient
      to produce relief from block. For 30 microM internal spermine such analysis gave
      Kd(O) = 2.5 microM, z theta = 1.97; block by 30 microM external spermine was
      weaker and less voltage dependent (Kd(O) = 37.8 microM and z delta = 0.55); delta
      and theta are electrical distances measured from the outside and inside,
      respectively. 6. Fits of the Woodhull equation for a permeable blocker adequately
      described both onset and relief from block by spermine over a wide range of
      membrane potentials. However, the rate constants and z delta values estimated for
      block by internal spermine predicted much stronger external block than was
      measured experimentally, and vice versa. 7. An Eyring rate theory model with two
      energy wells and three barriers explained qualitatively many characteristic
      features of the action of polyamines on GluRs, including biphasic I-V
      relationships, weaker block by external than internal spermine and low
      permeability.

PMID- 9279812
TI  - Agonist action of taurine on glycine receptors in rat supraoptic magnocellular
      neurones: possible role in osmoregulation.
AB  - 1. To evaluate the implication of taurine in the physiology of supraoptic
      neurones, we (i) investigated the agonist properties of taurine on glycine and
      GABAA receptors of supraoptic magnocellular neurones acutely dissociated from
      adult rats, using whole-cell voltage clamp, (ii) studied the effects of taurine
      and strychnine in vivo by extracellular recordings of supraoptic vasopressin
      neurones in anaesthetized rats, and (iii) measured the osmolarity-dependent
      release of endogenous taurine from isolated supraoptic nuclei by HPLC. 2. GABA,
      glycine and taurine evoked rapidly activating currents that all reversed close to
      the equilibrium potential for Cl-, indicating activation of Cl(-)-selective
      channels. Glycine-activated currents were reversibly blocked by strychnine (IC50
      of 35 nM with 100 microM glycine), but were unaffected by the GABAA antagonist
      gabazine (1-3 microM). GABA-activated currents were reversibly antagonized by 3
      microM gabazine, but not by strychnine (up to 1 microM). 3. Responses to 1 mM
      taurine were blocked by strychnine but not by gabazine and showed no additivity
      with glycine-induced currents, indicating selective activation of glycine
      receptors. Responses to 10 mM taurine were partially antagonized by gabazine, the
      residual current being blocked by strychnine. Thus, taurine is also a weak
      agonist of GABAA receptors. 4. In the presence of gabazine, taurine activated
      glycine receptors with an EC50 of 406 microM. Taurine activated at most 70% of
      maximal glycine currents, suggesting that it is a partial agonist of glycine
      receptors. 5. In vivo, locally applied strychnine (300 nM) increased and taurine
      (1 mM) decreased the basal electrical activity of vasopressin neurones in
      normally hydrated rats. The effect of strychnine was markedly more pronounced in
      water-loaded rats. 6. Taurine, which is concentrated in supraoptic glial cells,
      could be released from isolated supraoptic nuclei upon hyposmotic stimulation.
      Decreases in osmolarity of 15 and 30% specifically enhanced basal release of
      taurine by 42 and 124%, respectively. 7. We conclude that supraoptic neurones
      express high amounts of glycine receptors, of which taurine may be regarded as a
      major natural agonist. We postulate that taurine, which can be released in
      hyposmotic situations, acts on glycine receptors to exert an inhibitory control
      on magnocellular neurones during alterations of body fluid homeostasis,
      implicating an active participation of glial cells in this neuroendocrine
      regulatory loop.

PMID- 9279813
TI  - Rhythmic bursting of pre- and post-inspiratory neurones during central apnoea in
      mature mice.
AB  - 1. Stimulation of pulmonary vagal C fibres (PCFs) inhibits inspiration but the
      response pattern of respiratory rhythm-generating neurones is unknown. This study
      provides the first description of the effects of PCF stimulation on six different
      types of respiratory neurones located in the ventrolateral medulla of the mature
      mouse. 2. Studies were performed in both urethane-anaesthetized (1.5 g kg-1 I.P.)
      mature mice and in an arterially perfused working heart-brainstem preparation
      (WHBP). In both preparations the respiratory motor pattern of phrenic and
      recurrent laryngeal nerves were comparable. Stimulation of PCFs, using
      phenylbiguanide (2-5 micrograms) injected into the right atrium, evoked a similar
      respiratory and cardiac response pattern in both anaesthetized and perfused mice,
      which included: (i) a significant prolongation of the inter-inspiratory interval;
      (ii) an increase in the duration and amplitude of post-inspiratory (PI) activity;
      and (iii) an atropine-sensitive bradycardia (50-260 beats min-1). 3. In the WHBP,
      PCF stimulation evoked a depolarization (11 +/- 1 mV) and high frequency tonic
      discharge (up to 64 Hz) in ten out of twenty-one PI neurones. During the PCF
      induced prolongation of PI activity all other PI neurones (n = 11), as well as
      pre-inspiratory neurones (PreI; n = 11), displayed oscillations in membrane
      potential and/or rhythmic bursting at a similar frequency of 0.7-1.0 Hz. Other
      respiratory neurones recorded, including stage II expiratory neurones (n = 7),
      early- (n = 6), ramp- (n = 16) and late-inspiratory neurones (n = 4), ceased
      firing rhythmically during PCF stimulation. 4. The firing behaviour of PI and
      PreI neurones was assessed after switching to a low Ca2+ (0.2 mM)-high Mg2+ (5.25
      mM) perfusate to block synaptic transmission in the WHBP. In the absence of
      synaptic transmission, PreI neurones (n = 7/8) continued to discharge
      rhythmically, whereas all other respiratory cell types (including PI neurones, n
      = 5) fired tonically. 5. In conclusion, stimulation of PCFs elicits a reflex
      evoked prolongation of the PI phase of the respiratory cycle and excitation of PI
      neurones including rhythmic discharging. It is suggested that this rhythmic
      bursting depends on inhibitory connections from PreI neurones. The functional
      significance of these central 'apnoeic rhythms' are discussed.

PMID- 9279814
TI  - Desensitization shortens the high-quantal-content endplate current time course in
      frog muscle with intact cholinesterase.
AB  - 1. The desensitization induced by bath-applied carbachol or acetylcholine (ACh)
      and potentiated by proadifen (SKF 525A) was studied in the frog sartorius with
      intact synaptic acetylcholinesterase (AChE). 2. The reduction in the density and
      number of postsynaptic receptors produced by desensitization lowered the
      amplitude of the endplate currents (EPCs) and shortened the EPC decay when the
      quantal content (m) of the EPC was about 170 and when multiple release of quanta
      at single active zones was highly probably. The shortening of high-quantal
      content EPCs persisted for at least 15 min after the wash-out of agonists, at a
      time when the amplitude had recovered fully. 3. The decay times of the low
      quantal-content EPCs recorded from preparations pretreated with 5 mM Mg2+ (m
      approximately 70) and single-quantum miniature endplate currents (MEPCs) were not
      affected by carbachol, ACh or proadifen. 4. The desensitization of ACh receptors
      potentiated by proadifen, prevented completely the 6- to 8-fold prolongation of
      EPC which was induced by neostigmine inhibition of synaptic AChE. 5. It is
      assumed that high-quantal-content EPCs increase the incidence of multiple quanta
      release at single active zones and the probability of repetitive binding of ACh
      molecules which leads to EPC prolongation. The shortening which persists after
      complete recovery of the amplitude during wash-out of the exogenous agonist is
      probably due to 'trapping' of ACh molecules onto rapidly desensitized receptors
      and the reduced density of functional AChRs during the quantum action.

PMID- 9279815
TI  - Distribution of sarcomere length and intracellular calcium in mouse skeletal
      muscle following stretch-induced injury.
AB  - 1. The effect on sarcomere organization of stretching intact single skeletal
      muscle fibres by 50% of their optimum length (Lo) during ten consecutive short
      tetani was investigated. Stretch reduced tetanic force to 36 +/- 4% of the pre
      stretch condition. Sarcomere organization was analysed using both electron and
      confocal microscopy. For confocal microscopy the striation pattern was examined
      by fluorescently staining F-actin with rhodamine-phalloidin. 2. Electron
      microscopy revealed that fibres which had been stretched during contraction
      contained areas of severe sarcomere disorganization, as well as adjacent
      sarcomeres of normal appearance. 3. Confocal images of stretched fibres, which
      had been fixed and stained with rhodamine-phalloidin, showed focal regions of
      overstretched sarcomeres and regions where sarcomeres of adjacent myofibrils were
      out of alignment with each other. Analysis of all sarcomeres along the length of
      fibres showed regions of sarcomere inhomogeneity were distributed throughout the
      fibre length and cross-section. 4. Fibres were microinjected with the fluorescent
      [Ca2+]i indicator fura-2 before being stretched. Conventional wide-field
      fluorescence imaging microscopy showed that the tetanic [Ca2+]i was reduced after
      stretching but remained uniformly distributed. 5. This study confirms the finding
      that stretch-induced muscle injury has components caused by disorganization of
      the myofibrillar array and by failure of tetanic Ca2+ release. The structural
      damage is spatially heterogeneous whereas the changes in Ca2+ release appear to
      be spatially homogeneous.

PMID- 9279816
TI  - Dynamics of viscoelastic properties of rat cardiac sarcomeres during the
      diastolic interval: involvement of Ca2+.
AB  - 1. Cardiac sarcomere stiffness was investigated during diastole in eighteen
      trabeculae dissected from the right ventricle of rat heart. The trabeculae were
      stimulated at 0.5 Hz, in a modified Krebs-Henseleit solution (pH, 7.4; 25 degrees
      C). Sarcomere length (SL) was measured using high resolution (+/-2 nm) laser
      diffraction techniques. Force (F) was measured with a silicon strain gauge. 2. SL
      increased exponentially (amplitude, 25 +/- 9 nm; n = 15) throughout diastole.
      This increase occurred even at slack SL, showing that this phenomenon was due to
      an internal expansion. The majority of the muscles showed discrete spontaneous
      fluctuations of SL (amplitude < 20 nm) starting approximately 1 s after the end
      of the twitch. 3. The intracellular free Ca2+ concentration ([Ca2+]i) was
      measured from the fluorescence of microinjected fura-2 salt in seven trabeculae
      under the same experimental conditions. [Ca2+]i continuously declined (from 240
      to 90 nM) during diastole following a monoexponential time course (time constant,
      210-325 ms). 4. The stiffness of the sarcomere was evaluated at 10, 30, 50, 70
      and 90% of diastole using bursts (30 ms) of 500 Hz sinusoidal perturbations of
      muscle length (amplitude of SL oscillations < 30 nm). At 1 nM external Ca2+
      concentration ([Ca2+]o), the average stiffness modulus (Mod) increased from 9.3
      +/- 0.6 to 12 +/- 0.6 nN mm-2 micron-1 (n = 18; P < 0.05), while the average
      phase shift (phi) between F and SL signals decreased from 84 +/- 3 to 73 +/- 4
      deg (n = 18; P < 0.05) between 10 and 90% during diastole. The increase in Mod
      and the decrease in phi reversed when spontaneous activity occurred. When [Ca2+]o
      was raised to 2 mM, the stiffness time course reversed approximately 450 ms
      earlier, simultaneously with the occurrence of spontaneous activity. 5. Our
      results show that diastole is only an apparent steady state and suggest that the
      structural system responsible for the viscoelastic properties of the sarcomere is
      regulated by [Ca2+]i in the submicromolar range. Different possible origins of
      the dynamic changes in viscoelasticity during diastole are discussed.

PMID- 9279817
TI  - Mass spectrometric determination of HCO3- permeability and carbonic anhydrase
      activity in intact guinea-pig colon epithelium.
AB  - 1. A mass spectrometric method originally used in red blood cells was applied to
      suspensions of isolated colonocytes and intact colonic epithelium to measure the
      exchange of 18O between HCO3-, CO2 and H2O to determine intracellular carbonic
      anhydrase activity (Ai) and membrane bicarbonate permeability (P). 2. In
      suspensions of isolated guinea-pig colon epithelial cells, colonocytes, we found
      significantly higher values of Ai and P for cells derived from the proximal colon
      than for cells from the distal colon. In the case of Ai, this confirms earlier
      reports. 3. When the 18O exchange process was observed across the mucosal
      (apical) side of intact colon mucosa, the estimated values of Ai were identical
      to those obtained for isolated colonocytes, for both the proximal and the distal
      part of the colon. This is considered to be strong evidence that this method can
      be applied to a layer of intact epithelium as well as to cell suspensions. 4. The
      values of P obtained from the apical side of intact colon mucosa were 6 times
      higher than those estimated from measurements with isolated colonocytes. This
      indicates that the basolateral membrane of colon epithelium, which participates
      in the 18O exchange process in isolated colonocytes but not in the 18O exchange
      process across the apical side of intact mucosa, has a markedly lower bicarbonate
      permeability than the apical membrane. 5. When the 18O exchange process was
      observed across the serosal (basolateral) side of intact colon mucosa, the P
      values, as expected, were low compared with the apical side of intact mucosa.
      However, rather unexpectedly, the Ai values derived from these measurements were
      2-3 times lower than those obtained with isolated colonocytes. It appears
      possible that the latter finding is an artifact due to the submucosal tissue
      markedly slowing down CO2 diffusion from the bathing medium into the epithelial
      cells, thus causing an apparent fall in Ai. 6. Ai decreased and P increased with
      increasing temperature, as expected, when studied on the mucosal side of intact
      colon. This provides additional support for the validity of the method.

PMID- 9279818
TI  - Control of motor units in human flexor digitorum profundus under different
      proprioceptive conditions.
AB  - 1. Changing the posture of the human fingers can functionally 'disengage' the
      deep finger flexor muscle from its normal action on the terminal phalanx of the
      fourth (or third) finger. This enables the activity of the muscle to be studied
      both with and without its normal proprioceptive inputs. 2. Spike trains of long
      duration from pairs of concurrently active motor units in this muscle were
      recorded in both the engaged and disengaged hand postures. Subjects voluntarily
      kept one of the motor units (the 'controlled' unit) discharging at the same
      target frequency in both postures. The strength of short-term synchrony, the
      strength of common drive, and the variability of discharge of these pairs of
      motor units were determined in both postures. 3. All subjects reported that the
      effort required to activate the motor units in the disengaged hand posture was
      substantially greater than in the normal engaged posture. 4. Short-term
      synchrony, which is a function of common corticospinal inputs to pairs of motor
      units, was similar in both hand postures. However, the strength of common drive
      was significantly decreased when the muscle was disengaged. Although the neural
      substrate for common drive is not known, this observation suggests that
      proprioceptive feedback is involved either directly or indirectly. 5. Although
      the discharge rate of the 'uncontrolled' motor units increased when the muscle
      was disengaged, the variability of discharge of these and the 'controlled' motor
      units increased significantly. This supports the idea that the precision with
      which fine motor tasks can be performed is improved when proprioceptive feedback
      is intact.

PMID- 9279820
TI  - Toxicological correlation between changes in blood biochemical parameters and
      liver histopathological findings.
AB  - The toxicological correlation between blood biochemical parameters and liver
      histopathological findings was summarized mainly in rats and dogs on the basis of
      our experiments and published papers. In rats and dogs with hepatocytic necrosis,
      GPT and GOT increased with a good correlation to necrotic severity. In dogs with
      cholestasis, ALP, gamma-GTP, T.BIL and BSP retention rates increased. In mixed
      types of hepatitis or cholestasis and hepatic necrosis, GPT, GOT and ALP
      increased in rats and dogs and additionally gamma-GTP and BSP retention rates
      increased in dogs. In hepatic steatosis, CHOL and TRIG decreased in rats and
      dogs. In hepatic injury due to accumulation of foreign materials or cell
      components and sinusoidal cell injury, no specific correlation with biochemical
      parameters was noted.

PMID- 9279819
TI  - Anaplerotic processes in human skeletal muscle during brief dynamic exercise.
AB  - 1. This study examined changes in tricarboxylic acid cycle intermediates (TCAIs)
      in human skeletal muscle during 5 min of dynamic knee extensor exercise
      (approximately 80% of maximum workload) and following 2 min of recovery. 2. The
      sum of the seven measured TCAIs (sigma TCAIs) increased from 1.10 +/- 0.08 mmol
      (kg dry weight)-1 at rest to 3.12 +/- 0.24, 3.86 +/- 0.35 and 4.33 +/- 0.30 mmol
      (kg dry weight)-1 after 1, 3 and 5 min of exercise, respectively (P < or = 0.05):
      The sigma TCAIs after 2 min of recovery (3.74 +/- 0.43 mmol (kg dry weight)-1)
      was not different compared with 5 min of exercise. 3. The rapid increase in sigma
      TCAIs during exercise was primarily mediated by large changes in succinate,
      malate and fumarate. These three intermediates accounted for > 90% of the net
      increase in sigma TCAIs during the first minute of contraction. 4. Intramuscular
      alanine increased after 1 min of exercise by an amount similar to the increase in
      the sigma TCAIs (2.33 mmol (kg dry weight)-1) (P < or = 0.05). Intramuscular
      pyruvate was also higher (P < or = 0.05) during exercise, while intramuscular
      glutamate decreased by approximately 50% within 1 min and remained low despite an
      uptake from the circulation (P < or = 0.05). 5. The calculated net release plus
      estimated muscle accumulation of ammonia after 1 min of exercise (approximately
      60 mumol (kg wet weight)-1) indicated that only a minor portion of the increase
      in sigma TCAIs could have been mediated through the purine nucleotide cycle
      and/or glutamate dehydrogenase reaction. 6. It is concluded that the close
      temporal relationship between the increase in sigma TCAIs and changes in
      glutamate, alanine and pyruvate metabolism suggests that the alanine
      aminotransferase reaction is the most important anaplerotic process during the
      initial minutes of contraction in human skeletal muscle.

PMID- 9279821
TI  - Long-term, low-dose, cadmium-induced nephropathy with renal osteopathy in
      ovariectomized rats.
AB  - To establish an animal model of chronic cadmium nephropathy and osteopathy, we
      intraperitoneally administered 0.228 mg CdCl2 (Cd) or normal saline (NS) to 52
      female Sprague-Dawley (S.D.) rats 3 times a week for 16 months following
      ovariectomy (OV) or sham surgery (Sham), dividing the animals into three
      experimental groups (OV-Cd, Sham-Cd and OV-NS). Two groups of male S.D. rats were
      also administered Cd or NS (22 animals; Male-Cd and Male-NS). Cd-administered
      rats gained significantly less body weight than NS rats after 16 months of
      experiments with no signs of emaciation. Serum creatinine levels and Cd contents
      in the kidney had significantly increased in the Cd-administered rats. OV-Cd rats
      showed significant decreases in PTH levels and increases in calcium contents in
      the kidney and other organs. Kidneys of Cd-administered rats showed atrophy,
      dilatation, and interstitial fibrosis of tubules. Sclerosis and collapse of the
      glomeruli were observed in the Cd groups with no proliferation in mesangial cells
      or matrix. The Haversian canal system of the Cd-administered rats disappeared and
      was replaced by a large quantity of degenerated, necrotic, and restorative
      tissues. Bone histomorphometric parameters showed that osteoid volume and osteoid
      surface had significantly increased in the Male-Cd group. In contrast, decreases
      in bone mass and increases in fibrous tissue were found to be more prominent in
      the OV-Cd group. Our results have demonstrated for the first time that long-term,
      low-dose CdCl2 administration to ovariectomized S.D. rats is capable of inducing
      irreversible nephropathy with osteopathy exhibiting pathological and bone
      histomorphometric characteristics that are very similar to those of Itai-Itai
      disease.

PMID- 9279822
TI  - Induction of a sister-chromatid exchange by nitrogen oxides and its prevention by
      SOD.
AB  - Observations were made on the increase in the frequency of sister-chromatid
      exchanges (SCEs) induced by a nitric oxide (NO) releaser (NOR4) and NaNO2 in
      Chinese hamster lung cells (CHL/IU). During these observations, NaNO3 did not
      have any effect on SCE induction. NOR4- and NaNO2- induced SCE frequencies
      decreased due to treatment with bovine serum (10%), bovine serum albumin (BSA,
      0.1%, 1.0%), oxyhemoglobin (Hb, 10 microM), and superoxide dismutase (SOD, 250
      U/ml), but not with glutathione (oxidized and reduced forms), cysteine, cystine
      and catalase. NO2- concentrations decreased with Hb, but not with any other
      agent, indicating that NO and/or NO2- have a strong binding reaction with Hb. The
      mechanism for a decrease in genotoxicity due to SOD is still unclear. However, it
      would appear that S-nitrosothiols in the cells can be stabilized by SOD in
      consideration of the S-nitrosothiols stabilizing effect of SOD reported by
      Kowaluk et al. (1990). In the presence of NO and superoxide anions, genotoxicity
      seemed to be decreased by catalase and SOD, since the former decreases the
      superoxide anion-induced SCE frequency, and the latter, the NO-induced frequency.

PMID- 9279823
TI  - Reproductive toxicity, mutagenicity and antigenicity of pamiteplase (genetical
      recombination).
AB  - Pamiteplase (genetical recombination), YM866, is a novel recombinant modified
      human tissue-type plasminogen activator developed by Yamanouchi Pharmaceutical
      Co. Ltd., Tokyo, Japan. An intended route of administration in the clinical use
      of this drug is intravenous administration. We conducted an intravenous fertility
      and general reproduction studies of this drug in male and female rats and
      teratology study of this drug in rabbits at the dose levels of 0 (vehicle
      control), 0.1, 0.3 or 1 mg/kg/day. In the rat, no treatment-related abnormalities
      were observed up to the maximum dose in parental animals and their offspring. In
      the teratology study in rabbits, prolonged coagulation time at the injection site
      was observed at 0.3 mg/kg or more. One death and one abortion occurred at 1 mg/kg
      on days 22 and 23 of pregnancy, respectively. No toxic effects on the litters
      were observed up to the maximum dose. Results of evaluation of the mutagenicity
      of YM866 and its ability to induce chromosome aberrations using the L5178Y TK+/-
      mouse lymphoma assay, human lymphocyte chromosome aberration assay and the
      micronucleus assay in mice were negative. Evaluation of the immunogenicity of
      YM866 by repeated intravenous injection in chimpanzees elicited no confirmed
      antibody titers.

PMID- 9279824
TI  - Effect of hyperprolactinemia induced by neuroleptic agent, timiperone, on
      porphyrin content of mouse harderian gland.
AB  - The histology and porphyrin content of the Harderian gland and the serum
      prolactin levels were examined in male B6C3F1 mice treated with neuroleptic
      butyrophenones (timiperone and haloperidol) and treated concurrently with
      timiperone and 2-bromo-alpha-ergocryptine (bromocriptine), a potent suppressor of
      prolactin. Light-microscopically, both timiperone and haloperidol increased the
      number of accretions of porphyrin pigment within the Harderian gland lumina.
      Timiperone treatment of mice increased both the porphyrin content of the
      Harderian gland and the serum prolactin levels. Administration of bromocriptine
      to timiperone-treated mice distinctly prevented the rise in both tissue porphyrin
      and serum prolactin levels. In intact mice, bromocriptine also exerted inhibitory
      effects on both the Harderian gland porphyrin content and the serum prolactin
      level. Electron microscopic investigation revealed that the cytoplasm of type A
      cells in the Harderian glands of mice treated with timiperone contained
      trilaminar profiles similar to those seen in the intraluminar pigment masses.
      These results indicate that timiperone accelerates porphyrin secretion from the
      type A cells of the mouse Harderian gland by increasing the serum prolactin
      levels.

PMID- 9279825
TI  - Effect of blood collection imitating toxicokinetic study on rat hematological
      parameters.
AB  - The effect of blood collection imitating a one-month toxicokinetic study on
      hematological parameters was studied in male rats (6 weeks of age at the
      beginning of the experiment). Three groups were established according to blood
      sampling points per day; Group I (3 points), Group II (5 points) and Group III
      (10 points). These repeated blood samplings were carried out on the first and
      last days of this study, and one-point blood sampling was also done every week
      during the experiment. In each sampling, 0.3 ml of blood was collected from the
      jugular vein. There were no changes in Group I, but in other groups, especially
      in Group III, red blood cell counts, hematocrit and hemoglobin concentration
      decreased during repeated blood sampling. On the other hand, white blood cell
      counts also decreased, but recovered within 24 hr. Platelet counts did not show
      any decrement. From the present result, less than 0.9 ml of blood per day is
      conceivable as the volume without causing changes in hematological parameters.
      The baseline of the sampling volume can become one reference for toxicokinetic
      and toxicological studies.

PMID- 9279826
TI  - Results of a 28-month chronic inhalation toxicity study of formaldehyde in male
      Fisher-344 rats.
AB  - Male F-344 rats were exposed by inhalation to gaseous formaldehyde at 0.3, 2, and
      15 ppm 6 h/day, 5 days/week for 28 months. Nasal tumors were macroscopically
      evident in the 15 ppm group from the 14th month and 8 of 32 rats bore such tumors
      at the 24th month. Histopathological examination revealed both squamous cell
      papillomas and carcinomas. No nasal tumors were observed in the lower exposure
      groups (0.3 and 2 ppm groups). In the high exposure group (15 ppm group),
      frequent face washing, coughing and/or crouching position, lacrimation, nasal
      discharge, and yellow discoloration of the haircoat were observed. Significant
      decrease in food consumption and body weight was noted, and 20 (88.3%) rats died
      by the 24th month. Reduced triglyceride levels and liver weights, presumed to be
      related to the drop in food intake, were also seen in the 15 ppm group.
      Epithelial cell hyperplasia, hyperkeratosis, and the squamous metaplasia were
      apparent in all exposure groups. Inflammatory cell infiltration, erosion or edema
      were evident in all groups, including the 0 ppm and room (RC group) controls. In
      this study, a no effect level of formaldehyde vapor could not be obtained because
      toxicological signs were obvious even with the low exposure group. The benchmark
      doses for squamous metaplasia and epithelial hyperplasia were 0.25 and 0.24 ppm,
      respectively.

PMID- 9279827
TI  - A repeated-dose dermal toxicity study of hydrophobically modified hydroxypropyl
      methylcellulose in rats.
AB  - A six-month repeated-dose dermal toxicity study followed by a 30-day recovery
      test of hydrophobically modified hydroxypropyl methylcellulose (HM-HPMC), a new
      cellulose derivative used as a thickener for topical pharmaceuticals, was
      conducted using rats. Aqueous paste of HM-HPMC was applied to the skin of rats
      once daily at dose levels up to 60 mg/kg/day, which was the highest dose that
      could be administered. Items checked included general signs, urinalysis,
      hematology, ophthalmology, and histopathology. One rat died during the
      administration period owing to a malignant tumor in the hemopoietic system, which
      was not attributed to the test substance. Statistically significant differences
      were found in some test results, but those were not dose-dependent and were
      considered to be incidental or spontaneous. It was concluded that the test
      substance was not toxic upon chronic dermal administration at dose levels up to
      60 mg/kg/day.

PMID- 9279828
TI  - Obesity and the diet pill dilemma.

PMID- 9279829
TI  - Women's health care needs and use: data from the National Center for Health
      Statistics.

PMID- 9279831
TI  - Effect of body mass index on activity limitation and mortality among older women:
      the National Health Interview Survey, 1986-1990.
AB  - We assessed the impact of body mass on the association between activity
      limitations due to chronic conditions and mortality among 24,612
      noninstitutionalized white or African American women aged > or = 65 years who
      participated in a National Health Interview Survey between 1986 and 1990. We
      found that more African American women had activity limitations than white women
      (59% vs 46%, respectively). The difference by race was greatest (19% vs 10%) for
      the most severe limitation (unable to perform the major activity). For women aged
      65-69, the major activity was working or keeping house; for those aged > or = 70,
      it was the ability to live independently. For white women in all three categories
      of body mass index (BMI) and for African American women with BMI 15%-85%, the
      risk of dying was significantly higher for those unable to perform the major
      activity than for those with no limitations, controlling for the effects of
      education, marital status, and perceived health. The findings confirm the
      established link between low BMI and mortality and between activity limitations
      and mortality. Additionally, the findings further suggest that activity
      limitations linked to chronic conditions increase the risk of death within each
      stratum of BMI after adjusting for potential confounders.

PMID- 9279830
TI  - Postpartum mood disorders: clinical perspectives.
AB  - Mood disorders are common in women. A prepregnancy personal history of mood
      disorder (bipolar or major depression), premenstrual syndrome, or (possibly)
      postpartum blues places a woman at high risk for a postpartum exacerbation of
      symptoms. Untreated or unrecognized postpartum mood disorders can lead to serious
      psychologic and social consequences, in some cases even leading to suicide or
      infanticide. Women at risk for postpartum mood disorders need to be referred for
      psychiatric consultation before pregnancy and parturition. Informed, professional
      collaboration offers the best opportunities for prevention, as well as the
      earliest recognition and treatment of emergent symptoms.

PMID- 9279832
TI  - Parity, postmenopausal estrogen use, and cardiovascular disease risk factors in
      American Indian women: the Strong Heart Study.
AB  - Studies have suggested that high parity is related to an increased risk of
      cardiovascular disease (CVD). Reasons for an increased risk are unclear but may
      include influences of child-bearing on levels of CVD risk factors. The present
      study examined the associations of parity and CVD risk factors in American Indian
      women, among whom large families are common. Estrogen use and CVD risk factors
      also were assessed. The study included 1982 ever-married, postmenopausal women
      aged 45 through 74 years who participated in the Strong Heart Study (SHS), a
      large study of American Indians in three geographic areas of the United States.
      Information was obtained during a physical examination and interview. Parity
      ranged from 0 to 18 (median 5). Current estrogen use varied from 5% in Arizona to
      21% in Oklahoma. Multivariable analyses found a statistically significant,
      inverse association between parity and high-density lipoprotein (HDL)
      cholesterol, although the difference with increasing parity was small (-0.26
      mg/dl per additional live birth). Estrogen users had significantly lower levels
      of low-density lipoprotein cholesterol (-6.4 mg/dl) and fibrinogen (-26.2 mg/dl)
      and a lower waist/hip ratio (-0.02), and higher values of HDL (5 mg/dl) and
      logarithm (ln) triglyceride (0.13 mg/dl). Current users were slightly more likely
      to be hypertensive (prevalence odds ratio, 1.56). Relations between parity and
      CVD risk factors in American Indian women with high parity suggested only small
      differences with increasing parity. Associations with estrogen use are much
      stronger and are similar to those observed in other groups of women.

PMID- 9279833
TI  - Issues of sexuality in older women.
AB  - The aim of this exploratory research study was to investigate the attitudes of
      women over 60 toward sexuality and intimacy, to elicit which issues concerning
      sexuality and intimacy are important to them, and to gather their perceptions of
      how issues of sexuality and intimacy are addressed by the medical profession.
      Fourteen women aged 60-85 participated in three focus group interviews organized
      in Kingston, Ontario, Canada. We qualitatively measured recurring themes in
      attitudes about sexuality. Although they grew up in a generation when sex and
      sexuality were rarely discussed, these older women did not have any problem
      talking about sex, sexuality, and their attitudes towards these topics within the
      focus group setting. The participants felt on the whole, that sexuality is, and
      will continue to be, an important part of their lives. There was consensus that
      they would feel comfortable talking to their family doctor about their own or
      their partner's problems if asked but might not volunteer the information. Sex
      and sexuality are important issues to these older women. Male impotence is the
      most common problem that affects these older women's sex lives. They need more
      information about normal changes with aging that affect sexuality of older women
      and men. These women have rarely been afforded the opportunity to discuss
      sexuality with their physician. The small sample size of this pilot study
      provided useful information but is not definitive in its conclusions. Further
      research is needed to determine physician attitudes and practices concerning sex
      and sexuality in this age group.

PMID- 9279834
TI  - Women's beliefs and decisions about hormone replacement therapy.
AB  - To examine preventive health practices in older women, we conducted computer
      assisted telephone interviews with 1082 women aged 50-80 who were enrollees of
      Group Health Cooperative of Puget Sound (June-November 1995; 80.3% response
      rate). We sought to describe the women's reasons for initiating, discontinuing,
      or not initiating hormone replacement therapy (HRT). HRT use was categorized as
      current (42.5%), past (20.9%), or never (36.6%) based on the interviews. The
      reasons most frequently cited by current users for initiating HRT were menopausal
      symptoms (47.3%), osteoporosis prevention (32.4%), and physician advice (30.3%).
      The most frequently cited reasons for quitting HRT were side effects (26.6%),
      physician's advice (22.9%), fear of cancer (15.4%), and not wanting menstrual
      periods or bleeding (15.2%). Of past users, 53.8% reported stopping HRT on their
      own, and 46.2% did so at their physician's advice. The reasons most commonly
      cited by never users for not initiating HRT were that hormones were not needed
      (49.9%) and that menopause is a natural event (17.9%). Among never users, 33.1%
      reported considering HRT, only 46.6% discussing it with their provider, and 5.0%
      being given an HRT prescription they did not fill. Many women made decisions
      about HRT independent of interactions with health care providers. Better
      understanding of the beliefs and decisions that influence women's choice to use
      or not use HRT is needed to develop more effective counseling strategies.

PMID- 9279835
TI  - Perceptions of menopausal stage and patterns of hormone replacement therapy use.
AB  - In 1994, as part of their participation in the University of North Carolina
      Alumni Heart Study, 1101 women aged 45-51 years answered questions about their
      menopausal status and current use of hormone replacement therapy (HRT). Little is
      known about the use of HRT in younger women. We were interested in determining
      both patterns of HRT use and patient characteristics associated with HRT use in
      this cohort of women approaching the average age of menopause. After excluding
      women with breast, endometrial, and ovarian cancer, we studied 1080 women. These
      women identified themselves as: "There is no indication that I am near menopause"
      (stage 1, n = 326), "I think I may be close to or in the beginning stages of
      menopause but am not sure" (stage 2, n = 410), "I have begun menopause" (stage 3,
      n = 202), and "I have been through menopause" (stage 4, n = 142). The overall
      rate of HRT use was 22% (0% in stage 1, 8% in stage 2, 52% in stage 3, and 76% in
      stage 4). Both patterns of HRT use and patient characteristics associated with
      HRT use differed based on the woman's perception of her menopausal stage. In
      logistic regression models, where HRT use was the outcome variable, independent
      predictors of HRT use included stage of menopause, having had a hysterectomy,
      having had a bilateral oophorectomy, no family history of breast cancer, having
      had a pelvic examination in the last year, being married, and not participating
      regularly in physical exercise. A woman's perception of her stage in the process
      of reproductive aging correlates with her use of HRT. Informed decision making
      about HRT use should be tailored to the individual's perception of her menopausal
      stage.

PMID- 9279836
TI  - Women's perception of risk of coronary artery disease.

PMID- 9279837
TI  - Tamoxifen and endometrial cancer: tamoxifen effects on the human female genital
      tract.

PMID- 9279838
TI  - Cancer-associated human papillomavirus types are selectively increased in the
      cervix of women in the first trimester of pregnancy.

PMID- 9279839
TI  - Randomized controlled trial of superovulation and insemination for infertility
      associated with minimal or mild endometriosis.

PMID- 9279840
TI  - LiteratureWatch.

PMID- 9279841
TI  - HPV and Pap smears.

PMID- 9279842
TI  - Fibromyalgia: an important diagnosis to consider.

PMID- 9279843
TI  - A cost-effectiveness analysis of earwax softeners.

PMID- 9279844
TI  - Noninvasive evaluation of coronary artery disease and myocardial viability
      through stress echocardiography and myocardial perfusion imaging.
AB  - Today, primary care providers are managing clinical problems that were frequently
      addressed by a "specialist". Consequently, they must keep current with myriad
      state-of-the-art diagnostic modalities. In the case of coronary artery disease,
      knowledge about the reversibility of left ventricular dysfunction conceptualized
      as "hibernating" and "stunned" myocardium has resulted in an increased
      utilization of noninvasive cardiac imaging techniques to facilitate clinical
      decision making. These procedures provide diagnostic and prognostic information
      about coronary artery disease and left ventricular function beyond that provided
      by the conventional exercise stress test. The most commonly employed of these are
      the stress echocardiogram and stress myocardial nuclear perfusion procedures.
      Both modalities can be performed in conjunction with physical or
      pharmacologically induced stress, and may be performed on an outpatient basis.
      Knowledge of how these procedures are performed and the clinical data they
      provide will facilitate primary care providers as they care for this growing
      population.

PMID- 9279845
TI  - Physical activity in the elderly: benefits and intervention strategies.
AB  - In spite of the well-documented evidence that physical activity is beneficial,
      only 30% of individuals over the age of 65 report exercising regularly. Regular
      physical activity can minimize and prevent chronic problems and increase
      functional ability in the elderly. Designing physical activity for the elderly
      requires initial assessment of functional ability, exercise tolerance, physical
      limitations, and psychologic and social support of the individual. The exercise
      prescription should address the intensity, frequency, and duration of the
      exercise. Several factors affect the elderly's initiation and adherence to a
      physical activity program. These include the elder's perception of factors
      preventing physical activity, individual goal setting, and personal and therapist
      support in the effort.

PMID- 9279846
TI  - Infant formulas: practical answers for common questions.
AB  - The pediatric health care provider is often faced with myriad decisions related
      to the use of infant formula. This article compares human milk to cow's milk. It
      addresses the composition, classification, and use of some of the most common
      infant formulas manufactured for use with the term infant in the outpatient
      setting. Common clinical situations are discussed, including the role for low
      iron, goat's milk, and follow-up formulas, and formula use for the infant with
      diarrhea, colic, and atopic disease. The article highlights the poor quality of
      research and the lack of definitive answers available to the clinician when
      managing the infant with atopic disease. It concludes with a review of practical
      aspects of infant formula feeding for use in client education and management,
      including guidelines for formula preparation, calculating necessary formula
      intake, frequency, and quantity of infant feedings, and provisions of the WIC
      program.

PMID- 9279847
TI  - Bell's palsy: an update on idiopathic facial paralysis.
AB  - Patients with Bell's palsy, or idiopathic facial paralysis, present sporadically
      in the primary care setting. New evidence implicates reactivated herpes simplex
      virus (HSV) as the etiologic agent in greater than 70% of cases diagnosed as
      Bell's palsy. Careful evaluation of the patient with facial paralysis, including
      history, physical examination, and diagnostic assessment, may mandate the
      expeditious treatment of facial paralysis to prevent faulty nerve regeneration
      during the recovery period. Using the results of an objective tool for grading
      resting facial symmetry, symmetry of voluntary movement, and synkinesis can
      provide a quantitative measurement for decision making. These data are also
      useful in documenting progression or regression of the patient's facial
      paralysis. Administration of acyclovir with prednisone improves the recovery of
      complete facial functioning following an episode of Bell's palsy. During the
      acute and convalescent stages, the eye on the affected side must be protected
      until function is restored to the facial nerve. Residual effects of Bell's palsy
      lasting more than 6 months may indicate another diagnosis and the need to refer
      the patient to a specialist.

PMID- 9279848
TI  - Employment agreements: clauses that can change an NP's life.
AB  - An employment agreement is a legal contract that spells out the conditions of a
      working relationship between an employer and employee. Nurse practitioners (NPs)
      are being offered employment agreements. These documents are complex, lengthy,
      and require careful analysis. Three clauses commonly found in employment
      agreements are especially difficult to interpret and can have profound effects on
      an NP's life. These clauses are restrictive covenants, bonus formulas, and
      termination clauses. Restrictive covenants require an NP to promise-up front-not
      to compete with an employer when the present employment ends. Bonus formulas
      specify conditions under which an employer rewards an NP for superior
      performance. Termination clauses specify that an employer may end the agreement,
      without cause, with 30 days' notice. This article gives examples of each type of
      clause and advises NPs about how to negotiate reasonable terms.

PMID- 9279849
TI  - Clinical guidelines. Injury and domestic violence prevention.

PMID- 9279850
TI  - Diphtheria, pertussis, and tetanus vaccine (DPT).

PMID- 9279851
TI  - HIV and HAART in 1997. Highly active antiretroviral therapy.

PMID- 9279852
TI  - Medicare reimbursement: for NPs, CNSs, MDs, and Telehealth.

PMID- 9279853
TI  - The fenfluramine/phentermine combination for weight loss.

PMID- 9279854
TI  - Today's students, tomorrow's nurses: the future.

PMID- 9279855
TI  - Spending more through "cost control": our obsessive quest to gut the hospital.

PMID- 9279856
TI  - Overdrugging and undertreatment in primary health care.
AB  - Numerous strategies can be used as substitutes for drug therapy. However, using
      alternative and nonpharmacologic treatments on a routine basis, role modeling,
      and saying "no" to the demand for drugs and to marketing pressures are primary
      approaches. Most importantly, provision of education, counseling, and support
      through HCPs or through appropriate referral is a mainstay of care.

PMID- 9279857
TI  - The effect of managed care on breast cancer detection, treatment, and research.

PMID- 9279858
TI  - Persuasive communication: marketing health promotion.

PMID- 9279859
TI  - Sexual orientation: a cultural diversity issue for nursing.

PMID- 9279860
TI  - A framework for international health care consultations.

PMID- 9279861
TI  - Nurse staffing and quality of care in health care organizations research agenda
      of the Department of Health and Human Services, Agency for Health Care Policy and
      Research, National Institute for Nursing Research, Division of Nursing of HRSA.

PMID- 9279862
TI  - Alteration in capillary permeability of horseradish peroxidase in the stria
      vascularis and movement of leaked horseradish peroxidase after administration of
      furosemide.
AB  - The permeability of horseradish peroxidase (HRP) from the capillaries of the
      stria vascularis and the movement of leaked HRP in this site were investigated
      over time after the administration of furosemide, a loop diuretic, for the
      purpose of clarifying the function of the stria vascularis. Guinea pigs were used
      as experimental animals. The stria vascularis became markedly edematous at 10 min
      after the administration of furosemide, while the vascular permeability of HRP
      was decreased. This edema was thought to result not from the high permeation of
      strial capillaries, but from the blockage of water transport into the ductus
      cochlearis by inhibition of the Na+/2Cl-/K+ cotransport system on the cell
      membrane of the marginal cells and the exudation from the intermediate cells due
      to change of cell membrane permeability. A large amount of the leaked HRP from
      the strial capillaries was taken into vacuoles of marginal cells 1 h after
      furosemide administration. In the present study, no leakage of HRP was observed
      in the ductus cochlearis. Destroyed or degenerated cells were observed in
      vacuoles of marginal cells 2 and 3 h after furosemide administration, suggesting
      that marginal cells have a phagocytic function. Two hours after furosemide
      administration, the vascular permeability of HRP and the function of intermediate
      cells was still at a decreased level, although the stria vascularis was almost
      restored to normal morphology. Three hours after furosemide treatment, the
      vascular permeability of HRP and the intake of HRP into intermediate cell
      vesicles were generally normalized, suggesting near restoration of stria
      vascularis function. In the non-furosemide-treated control group, no vacuolation
      was observed in marginal cells, nor was HRP intake observed in these cells.

PMID- 9279863
TI  - Image analysis of neurofilament immunoreactivity in human spiral ganglion.
AB  - Computer-assisted image analysis was used to study the immunoreactivity to NF-L,
      NF-M and NF-H in human spiral ganglion cells. The concentrations, represented by
      the relative mean grey of NF-L, NF-M and NF-H, were calculated and compared. The
      cell-area mean-grey correlations for NF-L, NF-M and NF-H were analysed and
      calculated, showing that NF-M is more specific to the larger cells (type 1?) and
      NF-H is more specific for the smaller cells (type 2?), while NF-L is non-specific
      for cell size. These findings confirm several previous assumptions by providing a
      quantitative basis. We conclude that image analysis is a useful-even essential
      tool for the analysis of immunostained temporal bone sections.

PMID- 9279864
TI  - Effect of streptomycin on the otoconial layer of the guinea pig.
AB  - The effects of streptomycin on the otoconial layer of the adult guinea pig were
      investigated using scanning electron microscopy. Administration of streptomycin
      induced a reduction of otoconia with formation of giant otoconia. These phenomena
      reached their maximum 4 weeks after the cessation of streptomycin intoxication in
      the utricle and between 2 and 6 weeks after in the saccule. Otoconia began to
      recover in the utricle 4 weeks and in the saccule 6 weeks after the cessation of
      streptomycin intoxication with an increasing number of small otoconia. Eight or
      10 weeks after the cessation of streptomycin intoxication, the otoconial layer
      has completely recovered in both the utricle and saccule.

PMID- 9279865
TI  - Evaluation of the vertical semicircular canal function by the pendular rotation
      test: a study on patients with benign paroxysmal positional vertigo.
AB  - The pendular rotation test (non-damped) in a head-tilted position, 60 degrees
      backward and then rotated 45 degrees either to the right or left, was performed
      in 6 patients with benign paroxysmal positional vertigo. The stimulus mode was
      amplitude = 360 degrees, frequency = 0.1 Hz, and the maximal speed = 114
      degrees/s. By this test procedure, it was possible to evaluate the excitability
      of vertical semicircular canals. Using an infra-red CCD camera and a personal
      computer system, the evoked nystagmus was analysed. A statistically significant
      difference (p < 0.05) in the maximal slow-phase eye velocity of vertical
      nystagmus was found between those from the anterior semicircular canal and those
      from the posterior semicircular canal. The excitability of the posterior
      semicircular canal in the affected ear was found to be lower than that of the
      anterior semicircular canal.

PMID- 9279866
TI  - Intraoperative measurements of auditory-evoked potentials in three patients with
      acoustic neuroma.
AB  - Auditory brainstem responses (ABRs), electrocochleograms and the evoked
      potentials from the internal auditory canal were recorded simultaneously in 3
      acoustic neuroma (AN) patients. The neural conduction in the internal auditory
      canal was examined by recording the compound action potentials of the cochlear
      nerve. In an AN patient with wave I only in the ABR, the neural conduction of the
      excitement in the cochlear nerve was blocked within the internal auditory canal.
      In 2 AN patients with elongated interpeak latency differences between waves I and
      V in ABRs, the neural conduction velocity of the cochlear nerve was lower than
      that of normal subjects. These results provide neurophysiological evidence that
      low neural conduction velocity in the cochlear nerve results in the abnormal ABR.

PMID- 9279868
TI  - The impact of the measuring distance on laser-Doppler measurements of the
      microcirculation in human nasal mucosa. A study of rhinostereometry and
      micromanipulator-guided laser-Doppler flowmetry.
AB  - Fourteen healthy volunteers were examined using rhinostereometry (RSM) and
      micromanipulator-guided laser-Doppler flowmetry (LDF) on the inferior turbinate
      and nasal septum. There were significant differences of the flowmetry readings at
      different distances from the mucosal surface within 0-1.0 mm. Changes in LDF
      values due to a change in distance between probe and mucosa seem to be an
      important artefact that will influence the flowmetry, especially if the probe is
      fixed to the framework of the nose (i.e. the skull) and if the congestive status
      of the mucosa changes. This can be a problem especially during intranasal
      challenges with substances that influence congestion. These artefacts can be
      eliminated by using an RSM-guided micromanipulator that allows the probe to
      follow changes in congestion.

PMID- 9279867
TI  - Dehiscences of the horizontal segment of the facial canal in otosclerosis.
AB  - Dehiscences of the bony horizontal segment of the facial canal are rather common
      in human adults. These facial canal dehiscences occur most often in the region of
      the oval window. This study presents the observations of the facial canal in the
      oval window region in 427 operations for otosclerosis. The incidence of
      dehiscences in the facial canal to the middle ear space in otosclerosis was
      studied. Dehiscences were observed in 14 of the 427 patients (3.27%) who had a
      stapedotomy. This incidence is very low compared to the anatomical studies of the
      facial nerve in human cadaver temporal bones. Dehiscences of the facial canal are
      a variation of the normal anatomy of the facial nerve and these dehiscences occur
      sporadically in otosclerosis.

PMID- 9279869
TI  - Evaluation of the role of adenotonsillar hypertrophy and facial morphology in
      children with obstructive sleep apnea.
AB  - We evaluated the role of adenotonsillar hypertrophy and facial morphology in
      children with obstructive sleep apnea (OSA) and compared these data with an age
      matched control group. We performed cephalometric analysis to evaluate facial
      morphology using lateral facilal roentgenograms. Adenotonsillar and maxillary
      hypertrophy was remarkable in OSA children. Maxillary protrusion was
      significantly smaller in the OSA group than in the control group in older
      children (5-9 years old). Mandibular protrusion was significantly smaller in the
      OSA group even at younger ages (1-2 years old). The hyoid bone was significantly
      lower in the OSA group than in the control group at age 3-6 years. Both
      environmental factors due to upper airway obstruction and genetic factors are
      suspected as causes of abnormal facial morphology in OSA children.

PMID- 9279870
TI  - The possible effect of pregnancy on Meniere's disease.
AB  - There are few reports on the course of Meniere's disease during pregnancy. We
      report here the clinical course of Meniere's disease before, during and after
      pregnancy and discuss the possible effect of pregnancy on Meniere's disease and
      the treatment of Meniere's disease during pregnancy. In the present case, the
      vertigo attacks increased up to 10 times per month during early pregnancy, when
      the serum osmolality was significantly below normal at 268 mosm/kg. As the
      pregnancy proceeded, the serum osmolality normalized and the vertigo attacks
      decreased in frequency. The vertigo attacks were treated by oral isosorbide and
      intramuscular injection of low-dose diazepam. The coincidence of the decline in
      osmolality with the increase in vertigo attacks points to serum osmolality as a
      possible factor in the effect of pregnancy on Meniere's disease.

PMID- 9279871
TI  - Occult thyroid carcinoma manifested as a large mediastinal tumor.
AB  - The authors report a rare case of clinically occult thyroid carcinoma that
      initially manifested as a metastatic mediastinal tumor with tracheal stenosis. A
      curative operation was performed by complete removal of the tumor through a
      median sternotomy approach combined with resection of the tracheal invasion.
      Histopathological examination revealed transition of a well-differentiated
      papillary carcinoma into a poorly differentiated component in the lesion invading
      the trachea, which suggested that this transition might have rendered the tumor
      more aggressive, leading to tracheal invasion.

PMID- 9279872
TI  - Investigation of the nasopharyngeal bacterial flora in children with otitis media
      with effusion.

PMID- 9279873
TI  - Value of pharmaceutical sciences.

PMID- 9279874
TI  - Cmax/AUC, a commentary.

PMID- 9279875
TI  - Rational design of stable lyophilized protein formulations: some practical
      advice.

PMID- 9279876
TI  - Cooperation in pharmacy-drug wholesaler relations.
AB  - OBJECTIVE: The objective of this study was to investigate the associations
      between characteristics of pharmacy-wholesaler relations and cooperation in those
      relations. DESIGN/SAMPLE: Data were obtained from 326 pharmacies about 214
      pharmacy-primary wholesaler relations and 112 pharmacy-secondary wholesaler
      relations. MEASURES: Separate multiple regressions were performed to test the
      hypotheses for both types of pharmacy-wholesaler relationship. For each
      regression, cooperation was the dependent variable, while the independent
      variables were customer service level, trust, pharmacy influence, wholesaler
      influence, and duration of relations. RESULTS: For primary wholesalers (adjusted
      R-square = 0.59), three variables had significant associations with cooperation:
      trust, pharmacy influence, and customer service level. Conversely, the model for
      secondary wholesalers (adjusted R-square = 0.60) showed that only trust and
      pharmacy influence were significantly related to cooperation. CONCLUSIONS: Trust
      and perceived pharmacy influence are important to all wholesalers in fostering
      and maintaining cooperation from their customers. In addition, level of customer
      service is an important variable for primary wholesalers working to develop
      cooperation with their customers.

PMID- 9279877
TI  - Discrimination between rival dosing histories.
AB  - PURPOSE: In population pharmacokinetic studies, the dosing history is sometimes
      recorded in more than one way. The purpose of this study was to develop and
      evaluate a procedure for discriminating between rival dosing histories, i.e., for
      each individual in a data set, identify the dosing history that is the most
      plausible. METHODS: The procedure consists of four steps. In the first step we
      identify individuals whose dosing histories produce predictions that are
      consistent. In the second step these individuals are used to build a population
      pharmacokinetic model which is used, in step three, to select the dosing history
      for the individuals not identified in step one. In step four the population model
      is refined using the best available dosing histories for all individuals. The
      proposed procedure was evaluated using both simulations and a real data set, in
      which two dosing histories, based on patient diaries and electronic monitoring
      devices (MEMS) were available. RESULTS: In the real data set, estimated
      variabilities were almost always lower when the selected dosing histories were
      used compared to when no selection procedure was used. The diary dosing histories
      were selected more often than the MEMS dosing histories. In the simulations, the
      parameter estimates obtained using the selection procedure were closer to the
      true parameter values compared to when only one of the dosing histories was used.
      CONCLUSIONS: The proposed procedure appears to be robust and should be beneficial
      in at least two respects: improved parameter estimation of population
      pharmacokinetic and PK/PD models and objective information by which dosage
      recording methodologies can be compared and patient dose recording behavior can
      be assessed.

PMID- 9279878
TI  - Liposome-mediated therapy of intracranial brain tumors in a rat model.
AB  - PURPOSE: Malignant brain tumors represent a serious therapeutic challenge, and
      survival often is low. We investigated the delivery of doxorubicin (DXR) to rat
      brain tumors in situ via liposomes, to test the hypothesis that intact liposomes
      undergo deposition in intracranial tumor through a compromised blood-tumor
      vasculature. Both therapeutic effect and intra-tumor drug carrier distribution
      were evaluated to identify variables in carrier-mediated delivery having impact
      on therapy. METHODS: The rat 9L gliosarcoma tumor was implanted orthotopically in
      Fischer 344 rats in the caudate-putamen region. The tumor-bearing rats were
      treated with DXR, either free or encapsulated in long-circulating, sterically
      stabilized liposomes. Anti-tumor efficacy was assessed by survival time. In
      parallel, liposomes labeled with a fluorescent phospholipid analog were injected
      into tumor-bearing rats. At predetermined intervals, the brains were perfused
      with fixative, sectioned, and imaged with laser scanning confocal microscope
      (LSCM) to investigate the integrity of the tumor vascular bed and the intratumor
      deposition of liposomes. RESULTS: Free DXR given in 3 weekly iv injections was
      ineffective in increasing the life span of tumor-bearing rats at cumulative doses
      < or = 17 mg/kg, and at the highest dose (17 mg/kg) decreased survival slightly,
      compared to saline-treated controls. In contrast, DXR encapsulated in long
      circulating liposomes mediated significant increases in life span at 17 mg/kg.
      Rats showed a 29% percent increase in median survival, respectively, compared to
      saline-control animals. The delay of treatment after tumor implantation was a
      major determinant of therapeutic effect. Fluorescent liposomes were deposited
      preferentially in tumor rather than normal brain, and were distributed non
      uniformly, in close proximity to tumor blood vessels. CONCLUSIONS: Liposomes can
      be used to enhance delivery of drugs to brain tumors and increase therapeutic
      effect. The therapeutic effect may arise from release of drug from liposomes
      extravasated in discrete regions of the tumor vasculature and the extravascular
      space.

PMID- 9279879
TI  - Pharmacokinetic analysis of benzodiazepine receptor binding of [123I]iomazenil in
      human brain.
AB  - PURPOSE: The purpose of this study is to evaluate the central benzodiazepine
      (BZP) receptor binding of iomazenil (IMZ) by pharmacokinetic analysis and to
      establish a methodology for the diagnosis of CNS disorders with abnormalities in
      BZP receptor binding. METHODS: BZP receptor binding of IMZ was analyzed
      kinetically using plasma concentration-time profiles and dynamic single photon
      emission computed tomography (SPECT) data obtained after the intravenous
      administration of IMZ to patients with neuropsychiatric disease. The analysis was
      based on a 3-compartmental model including the processes of both blood-brain
      barrier (BBB) transport and BZP receptor binding. RESULTS: Hydrolized metabolite
      of IMZ was detected in plasma, indicating the need for separation by HPLC. The
      BBB influx clearance and the receptor binding potential of IMZ in the medial
      temporal region was reduced in the epileptic patient. CONCLUSIONS: Our findings
      suggest the possibility of detecting the epileptic focus by using our method.

PMID- 9279880
TI  - Metabolism of azetirelin, a new thyrotropin-releasing hormone (TRH) analogue, by
      intestinal microorganisms.
AB  - PURPOSE: We evaluated the effect of luminal bacterial metabolism on intestinal
      absorption of azetirelin in rats. In vitro characteristics of bacterial
      metabolism of azetirelin were also investigated with the goal of overcoming the
      low stability of the peptidic drug against luminal microorganisms. METHODS:
      Plasma azetirelin levels after oral administration to antibiotic-pretreated rats
      was examined. In vitro incubation experiments with bacterial suspensions were
      also performed to clarify the location of azetirelin breakdown activity as well
      as the effects of oxygen, pH, and various protease inhibitors on drug metabolism.
      RESULTS: Plasma azetirelin levels were sustained after oral administration to
      antibiotic-treated rats. Incubation with rat luminal contents demonstrated that
      azetirelin was metabolized by anacrobic bacteria, which are predominant in the
      distal intestine. Fecal suspensions from rats, dogs, and humans showed comparable
      metabolic activity. Azetirelin breakdown in the bacterial suspension was pH
      dependent and was inhibited in the presence of bacitracin or puromycin.
      CONCLUSIONS: Bacterial metabolism influences the degree of absorption of
      azetirelin in the distal intestine. Control of the luminal pH environment may be
      a practical method for improving the stability of azetirelin against intestinal
      microorganisms.

PMID- 9279881
TI  - Hepatic extraction of hexarelin, a new peptidic GH secretagogue, in the isolated
      perfused rat liver.
AB  - PURPOSE: To assess the hepatic extraction of hexarelin (HEX), a novel peptidyl GH
      secretagogue, in the isolated perfused rat model and document the in vitro
      binding of HEX to plasma proteins using plasma from rats, dogs, pigs, and humans.
      METHODS: Rat liver was perfused in situ using a recirculating system. The
      recirculating perfusate consisted of a Krebs Henseleit buffer containing 20%
      (v/v) prewashed bovine red blood cells, 1% albumin, and lg/L dextrose. Three HEX
      concentrations of 5, 50, and 500 ng/ml were examined. In vitro plasma binding was
      determined by the ultrafiltration method. RESULTS: The disappearance rate
      constant (K), half-life (t1/2), clearance (Cl), and hepatic extraction ratio (E)
      were: K = 0.013-0.014 min-1, t1/2 = 45-55 min, Cl = 0.345-0.401 ml/min/g liver,
      and E = 19-21% for the different concentrations of HEX. A linear increase in AUC
      (270-24334 min pmol/ml) was observed with increasing concentrations. Binding of
      HEX to plasma proteins of rats, dogs, pigs, and humans was 68.7 +/- 0.8%, 78.7 +/
      0.6%, 67.3 +/- 0.7%, and 65.2 +/- 0.6% respectively. Plasma binding was
      concentration-independent in the range between 0.003-3 microM for the four
      species examined. CONCLUSIONS: These results show that 1) the hepatic extraction
      of HEX is low, 2) the hepatic clearance is concentration independent up to 500 ng
      HEX/ml of perfusate, and 3) the plasma protein binding of HEX is significant over
      the dose range studied. HEX exhibits a low hepatic extraction ratio, allowing us
      to predict that its hepatic clearance may be limited upon HEX protein binding.

PMID- 9279882
TI  - Comparison of the disposition of hepatically-generated morphine-3-glucuronide and
      morphine-6-glucuronide in isolated perfused liver from the guinea pig.
AB  - PURPOSE: Humans and guinea pigs metabolise morphine extensively, forming the
      isomers morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in
      relatively similar ratios. Both metabolites are formed in the liver, and their
      greater polarity relative to the parent aglycone may limit their permeability
      across hepatic membranes. This study compared the disposition of hepatically
      generated M3G and M6G in perfused livers isolated from guinea pigs. METHODS:
      Livers were perfused at 30 ml/min in a non-recirculating manner with Krebs
      bicarbonate buffer containing morphine (6 to 7 microM). Perfusing medium, venous
      perfusate and bile were collected at regular intervals and concentrations of
      morphine, M3G and M6G determined by reversed-phase HPLC. RESULTS: Concentrations
      of morphine, M3G and M6G in perfusate and the rates of biliary excretion of M3G
      and M6G were consistent between 20 and 50 min of perfusion. The mean (+/-s.d.)
      ratio for the rate of formation of M3G relative to M6G was 3.7 +/- 1.5. A mean 33
      +/- 3% of morphine extracted by the liver was recovered as summed M3G and M6G. Of
      the M3G and M6G formed during a single passage, 19 +/- 11% and 9 +/- 9%,
      respectively, was excreted into bile; the values were significantly different (P
      = 0.002). CONCLUSIONS: A greater fraction of hepatically-generated M3G excreted
      into bile compared to that for M6G reflects differences in their relative
      transport across sinusoidal and canalicular membranes of hepatocytes, possibly
      via carrier-mediated systems.

PMID- 9279883
TI  - Comparison of CYP3A activities in a subclone of Caco-2 cells (TC7) and human
      intestine.
AB  - PURPOSE: To compare the activity of the CYP3A enzyme expressed by TC7, a cell
      culture model of the intestinal epithelial cell, to the activity of human
      intestinal CYP3A4, using terfenadine as a substrate. METHODS: The metabolism of
      terfenadine was investigated in intact cells and microsomal preparations from
      TC7, human intestine, and liver. The effect of two CYP3A inhibitors, ketoconazole
      and troleandomycin (TAO), on the metabolism of terfenadine was also examined.
      RESULTS: Only hydroxy-terfenadine was detected in TC7 microsomal incubations. In
      contrast, azacyclonol and hydroxy-terfenadine were detected in human intestinal
      and hepatic microsomal incubations. The Km values for hydroxy-terfenadine
      formation in TC7 cells, intestine and liver microsomes were 1.91, 2.5, and 1.8,
      microM respectively. The corresponding Vmax values were 2.11, 61.0, and 370
      pmol/min/mg protein. Km values for azacyclonol in intestinal and hepatic samples
      were 1.44 and 0.82 microM and the corresponding Vmax values were 14 and 60
      pmol/min/mg protein. The formation of hydroxy-terfenadine was inhibited by
      ketoconazole and TAO in human intestine and TC7 cell microsomes. The Km and Vmax
      values for terfenadine metabolism in intact TC7 cells were similar to those from
      TC7 cell microsomes. CONCLUSIONS: Our results indicate that TC7 cells are a
      potentially useful alternative model for studies of CYP3A mediated drug
      metabolism. The CYP3A expressed by TC7 cells is not CYP3A4, but probably CYP3A5,
      making this cell line suitable for studies of colonic drug transport and
      metabolism.

PMID- 9279884
TI  - Prodrug and analog approaches to improving the intestinal absorption of a cyclic
      peptide, GPIIb/IIIa receptor antagonist.
AB  - PURPOSE: The purpose of this study was to test whether structural modifications
      improve the intestinal absorption of DMP 728 (cyclo(D-Abu-NMeArg-Gly-Asp-Amb)), a
      GPIIb/IIIa receptor antagonist. METHODS: In vitro permeabilities of prodrugs and
      analogs of DMP 728 across excised rat intestinal segments were determined.
      RESULTS: n-Butyl and n-octyl esters of DMP 728 were relatively stable during in
      vitro permeation of rat intestine. Intestinal permeation rates of these compounds
      were no greater than that of DMP 728, even though the octyl ester was much more
      lipophilic. A pivaloyloxymethyl ester, which was hydrolyzed to DMP 728 during
      intestinal permeation, also did not improve permeability. In another approach,
      analogs with an additional methyl substituent on various amide nitrogens were
      evaluated. Cyclo(D-Val-NMeArg-Gly-Asp-NMeAmb), cyclo(D-Abu-diN-MeLys-Gly-Asp
      Amb), and cyclo(NMeGly-NMeArg-Gly-Asp-Amb) each had about 2-fold greater
      permeability than DMP 728. Two other analogs with improved permeability were
      linear Ac-D-Abu-NMeArg-Gly-Asp-Amb and a DMP 728 derivative in which the Asp was
      rearranged. An analog in which the charged amino acids were replaced by neutral
      amino acids had permeability similar to DMP 728. CONCLUSIONS: Within this series
      of peptides, hydrogen bonding tendency and structural constraint influenced
      intestinal permeation, but not always in ways consistent with the literature,
      whereas charge and lipophilicity were not shown to influence intestinal
      permeability. The failure of these approaches to improve permeation more
      significantly could be due to the influence of secretory transport.

PMID- 9279885
TI  - Mechanisms of food effects of structurally related antiarrhythmic drugs,
      disopyramide and bidisomide in the rat.
AB  - PURPOSE: To determine whether the rat is a good animal model for the food effects
      observed with bidisomide but not with the structurally similar antiarrhythmic
      drug, disopyramide in man and to explore a reason for the differences in the food
      effects of these compounds. METHODS: The following effects on the absorption of
      bidisomide and/or disopyramide were examined in the rat: Food effects,
      gastrointestinal transit time under fasting and nonfasting conditions, pH
      effects, hypertonic solution effect of NaCl and glucose, bile effects,
      permeability, inhibitory effects by Gly, Gly-Gly, Gly-Pro, glucose and mannitol
      and drug binding to food. RESULTS: Remarkable food effects were observed with
      bidisomide but not with disopyramide. There was no difference in the GI transit
      time with and without food. The pH effect with and without food was similar.
      Effect of salt concentrations on bidisomide and disopyramide was similar. There
      was no bile effect on absorption of both compounds. Binding of bidisomide and
      disopyramide to food was similarly low. The apparent permeability of bidisomide
      was much lower than disopyramide especially in the ileum and its absorption was
      more inhibited by Gly, Gly-Gly and Gly-Pro. CONCLUSIONS: In the rat, as
      previously seen in humans, the food effect was observed with bidisomide but not
      with disopyramide. This difference was in part due to both lower intestinal
      permeability of bidisomide compared to disopyramide and greater inhibition of
      absorption by the amino acid, Gly and the dipeptides, Gly-Gly and Gly-Pro.

PMID- 9279886
TI  - Consolidation mechanisms of pharmaceutical solids: a multi-compression cycle
      approach.
AB  - PURPOSE: The consolidation behavior of various pharmaceutical solids were
      characterized using compression-cycle profiles. Compression-cycle profiles for
      both uncompacted powder and formed tablets were obtained. These profiles were
      used to qualitatively and quantitatively characterize the consolidation mechanism
      of pharmaceutical solids. METHODS: An Instron Universal Testing apparatus and a
      specially instrumented die coupled with a computerized data acquisition system
      were utilized to measure the upper-punch pressure and the corresponding die-wall
      pressure during the compression cycle. RESULTS: Compression cycle profiles were
      obtained for a variety of pharmaceutical materials. Based on these profiles,
      parameters such as hysteresis areas, loading slopes, and unloading slopes were
      calculated for the materials studied. CONCLUSIONS: Materials that consolidate by
      plastic deformation have similar compression cycle profiles for the first and
      subsequent compression cycles indicating that the plastic deformation process
      occurs to the same extent on the first as well as subsequent compression cycles.
      For brittle materials, the brittle fracture process occurs during the first
      compression cycle. During subsequent cycles the tabletted material does not
      undergo further yield or failure and primarily undergoes elastic deformation. Low
      molecular-weight polyethylene glycol is an excellent model material for
      plastically deforming materials, whereas sucrose or sodium citrate are excellent
      examples of materials that consolidate by brittle fracture.

PMID- 9279887
TI  - Determination of extent of formaldehyde-induced crosslinking in hard gelatin
      capsules by near-infrared spectrophotometry.
AB  - PURPOSE: To predict the degree of crosslinking from formaldehyde-stressed hard
      gelatin capsules (HGCs) using near-infrared spectrophotometry (NIR). METHODS:
      HGCs were exposed to a 150 ppb atmosphere of formaldehyde for 2.25, 4.60, 9.42,
      16.0 and 24.0 hours. The capsules were filled with fresh amoxicillin, placed in a
      90 degrees conical reflector cone, and scanned in a NIR spectrophotometer.
      Principal component regression (PCR) was employed to analyze the spectra of the
      intact capsules. Dissolution profiles were then obtained for each experimental
      group. RESULTS: The dissolution of amoxicillin from the capsules at pH 1.2 was
      found to decrease with increasing time of exposure to the formaldehyde
      atmosphere. A set of principal components (PCs) was formed by a linear
      combination of the absorbance values at each wavelength scanned. A good
      correlation was established (r2 = 0.963) when PC values from the NIR spectra of
      the HGCs were regressed against percentage of amoxicillin dissolved at 45
      minutes, at pH 1.2. Water content of the capsules was found to be the largest
      determinant in the variation between HGC spectra at each exposure time.
      CONCLUSIONS: NIR spectrophotometry, combined with PCR, was successful at not only
      predicting dissolution of HGCs exposed to formaldehyde, but also at determining
      which wavelengths contributed most to spectral variation of these stressed HGCs.

PMID- 9279888
TI  - Circulatory concentrations of fibrinolytic species during thrombolytic therapy
      estimated by stirred-tank reactor analysis.
AB  - PURPOSE: A model for calculating the circulatory concentrations of fibrinolytic
      species is proposed and the findings are compared to reported values where
      available. METHODS: The model uses a CSTR analysis with fourth order Runge-Kutta
      solution of the differential equations to determine concentration profiles of key
      fibrinolytic species as a function of time during fibrinolytic therapy.
      Concentrations of the species are also determined for various dosage regimens of
      streptokinase and plasminogen. RESULTS: Data calculated by the model is in
      agreement with general experimental trends determined in vitro and in vivo.
      CONCLUSIONS: The proposed model can be used to predict concentration profiles of
      key fibrinolytic species during administration of streptokinase.

PMID- 9279889
TI  - Effect of vehicles and penetration enhancers on the in vitro and in vivo
      percutaneous absorption of methotrexate and edatrexate through hairless mouse
      skin.
AB  - PURPOSE: Low-dose methotrexate (MTX) is approved for the treatment of
      recalcitrant rheumatoid arthritis (RA). The objective of this study was to
      determine the effect of vehicles and penetration enhancers on the percutaneous
      absorption of MTX and its analog edatrexate (EDAM), and develop transdermal (TD)
      delivery systems of the drugs for the treatment of RA. METHODS: From previously
      published pharmacokinetic parameters with low-dose MTX therapy, and considering a
      50 cm2 diffusional area, the target steady state in vitro TD flux for MTX was
      calculated to be 35 micrograms/cm2/hr. Modified Franz diffusion chambers and
      hairless mouse skin were used for in vitro skin permeation studies. Hairless mice
      were used for in vivo studies. Delivered amounts of MTX and EDAM were determined
      by assaying the receiver phase fluid (or blood) with validated reversed phase
      HPLC methods. RESULTS: Intrinsic partition coefficient of MTX was low (log P = 
      1.2). Target MTX fluxes of > or = 35 micrograms/cm2/hr were achievable only with
      1-15% (v/v) Azone in propylene glycol (PG). Flux of EDAM (85 micrograms/cm2/hr)
      was higher than MTX from an isopropyl alcohol (IPA)-5% (v/v) Azone system.
      Clinically significant steady state in vivo blood concentration of MTX and EDAM
      was achieved using delivery systems containing > or = 2.5% Azone in PG. Area
      under the drug concentration-time curves (AUC0-24 hr) for MTX were 2379 and 3534
      ng*hr/ml from PG-2.5% Azone and PG-7.5% Azone systems respectively. AUC0-24 hr of
      EDAM was 6893 ng*hr/ml using a PG-2.5% Azone system. CONCLUSIONS: Results of this
      study show the feasibility of using a transdermal delivery system of MTX and EDAM
      for the treatment of rheumatoid arthritis.

PMID- 9279890
TI  - Simultaneous in vivo visualization and localization of solid oral dosage forms in
      the rat gastrointestinal tract by magnetic resonance imaging (MRI).
AB  - PURPOSE: Bioavailability of orally administered drugs is much influenced by the
      behavior, performance and fate of the dosage form within the gastrointestinal
      (GI) tract. Therefore, MRI in vivo methods that allow for the simultaneous
      visualization of solid oral dosage forms and anatomical structures of the GI
      tract have been investigated. METHODS: Oral contrast agents containing Gd-DTPA
      were used to depict the lumen of the digestive organs. Solid oral dosage forms
      were visualized in a rat model by a 1H-MRI double contrast technique (magnetite
      labelled microtablets) and a combination of 1H- and 19F-MRI (fluorine-labelled
      minicapsules). RESULTS: Simultaneous visualization of solid oral dosage forms and
      the GI environment in the rat was possible using MRI. Microtablets could
      reproducibly be monitored in the rat stomach and in the intestines using a 1H-MRI
      double contrast technique. Fluorine-labelled minicapsules were detectable in the
      rat stomach by a combination of 1H- and 19F-MRI in vivo. CONCLUSIONS: The in vivo
      1H-MRI double contrast technique described allows solid oral dosage forms in the
      rat GI tract to be depicted. Solid dosage forms can easily be labelled by
      incorporating trace amounts of non-toxic iron oxide (magnetite) particles. 1H-MRI
      is a promising tool for observing such pharmaceutical dosage forms in humans.
      Combined 1H- and 19F-MRI offer a means of unambiguously localizing solid oral
      dosage forms in more distal parts of the GI tract. Studies correlating MRI
      examinations with drug plasma levels could provide valuable information for the
      development of pharmaceutical dosage forms.

PMID- 9279891
TI  - Spreading and retention of vaginal formulations in post-menopausal women as
      assessed by gamma scintigraphy.
AB  - PURPOSE: In this paper we report on the first scintigraphic evaluation of vaginal
      dosage forms in post-menopausal women. To date, almost nothing is known about the
      in vivo performance of pharmaceutical formulations in the human vagina, which is
      a major deficiency in the rational design of drug delivery systems for both
      existing and new indications. METHODS: The vaginal spreading and clearance of a
      radiolabelled pessary formulation and Replens (polycarbophil) gel, was assessed
      in six healthy, post-menopausal female volunteers over a six hour period using
      the technique of gamma scintigraphy. RESULTS: In five out of the six subjects
      studied, clearance of the two formulations exhibited very little intra-subject
      variation. However, there was considerable inter-subject variability in
      clearance; in Subject 5 circa 80% of the products were retained whilst in Subject
      2 less than 2% was present at the end of the six hour imaging period.
      Importantly, there was no evidence to suggest that either of the formulations
      dispersed material beyond the cervix, into the uterus, in any of the subjects
      studied. CONCLUSIONS: The lack of significant retention of these products in most
      of the volunteers has obvious implications for the delivery of therapeutic
      agents. This study shows that gamma scintigraphy is an invaluable technique with
      which to assess novel formulations aimed at optimising retention in the vagina
      for topical or systemic drug delivery.

PMID- 9279892
TI  - Studies on the mechanism of absorption of depot neuroleptics: fluphenazine
      decanoate in sesame oil.
AB  - PURPOSE: The purpose of the present study was to investigate the pharmacokinetic
      characteristics of fluphenazine (FLU) and its decanoate (FLU-D) after intravenous
      and intramuscular administration to dogs. METHODS: A group of four beagle dogs
      was used in all intravenous and intramuscular experiments, with washout periods
      of no less than three months between doses. RESULTS: After intravenous FLU-D, the
      pharmacokinetics of the prodrug (mean +/- SD) were as follows: Clearance (CL)
      42.9 +/- 6.3 L/h; terminal half-life (t1/2) 3.5 +/- 0.8 h; volume of distribution
      (Vd) 216 +/- 61 L. The fractional availability of FLU was 1.0 +/- 0.2. After
      intravenous FLU, the volume of distribution of FLU (51 +/- 17.8 L) was some 4
      fold less than that of the prodrug. Simulations (Stella II) suggested that the
      rate limiting step was slow formation of FLU from the prodrug in the tissue
      compartment. After intramuscular FLU-D in sesame oil, the apparent t1/2 of FLU
      was 9.7 +/- 2.0 days whereas after intramuscular FLU base in sesame oil, the
      apparent t1/2 was only 7.7 +/- 3.4 h showing that the absorption of FLU itself
      from the intramuscular site and proximal lymph nodes is relatively rapid.
      CONCLUSIONS: The rate limiting step after intramuscular FLU-D appeared to be the
      slow partitioning of the prodrug out of the sesame oil at the injection site and
      in proximal lymph nodes.

PMID- 9279893
TI  - Carboxyl-directed pegylation of brain-derived neurotrophic factor markedly
      reduces systemic clearance with minimal loss of biologic activity.
AB  - PURPOSE: Brain-derived neurotrophic factor (BDNF) was modified by carboxyl
      directed protein pegylation in order to both retain biologic activity of the
      neurotrophin and reduce the rate of systemic clearance of this cationic protein
      in vivo. Since the modification of surface lysine residues of neurotrophins
      results in loss of biologic activity, the present studies examine the feasibility
      of placing polyethyleneglycol (PEG) polymers on carboxyl residues of surface
      glutamate or aspartate residues of BDNF. METHODS: PEG molecules with terminal
      hydrazide (Hz) moieties of molecular weight 2,000 (PEG2000-Hz) or 5,000 (PEG5000
      Hz) Daltons were coupled to BDNF carboxyls using carbodiimide. RESULTS: The
      systemic clearances of the BDNF-PEG2000 and BDNF-PEG5000 were reduced 67% and
      91%, respectively, compared to unconjugated BDNF. The brain volume of
      distribution (VD) of BDNF-PEG5000 was not significantly different from the
      cerebral plasma volume. Cell survival studies and TrkB auto-phosphorylation
      assays showed that the biologic activity of BDNF was not changed following
      pegylation with PEG2000, and was minimally impaired following pegylation with
      PEG5000. CONCLUSIONS: These experiments describe the first carboxyl-directed
      pegylation of a neuropeptide, and show this formulation substantially reduces the
      systemic distribution and elimination of the neurotrophic factor. The biologic
      activity of the neurotrophin is retained with carboxyl-directed pegylation.

PMID- 9279895
TI  - Cocaine pharmacokinetics/pharmacodynamics in awake freely moving rats.

PMID- 9279896
TI  - Can repeated plasma donation by asymptomatic HIV-infected individuals delay the
      onset of AIDS?
AB  - Healthy HIV-positive regular donors of plasma in a programme of passive
      immunotherapy for AIDS patients were studied over a period of about two years.
      None developed symptoms of clinical progression; most seemed to make substantial
      gains of CD4 cells by comparison with asymptomatic individuals who were not
      donating. The effects of donation did not seem to diminish with repetition, and
      donor CD4 counts tended towards stabilizing within normal limits. Asymptomatic
      HIV-positive individuals were compared immunologically with 'normals' and people
      with AIDS, using a battery of 25 measurements on peripheral blood. The
      immunological profiles of donor and non-donor asymptomatics, indistinguishable at
      the start, became dissimilar: donors' profiles resembled AIDS less, non-donors
      became less like 'normal' and a few non-donor results could not be distinguished
      from AIDS. Improvement in the CD4 counts and amelioration of the immunological
      profile in donors provide prima facie evidence that plasmapheresis may be
      therapeutic for asymptomatic HIV-positive people. Further studies are justified.

PMID- 9279894
TI  - Evaluation of genetic stability of recombinant human factor VIII by peptide
      mapping and on-line mass spectrometric analysis.
AB  - PURPOSE: The genetic stability of a recombinant human factor VIII (rhFVIII)
      product expressed in Chinese hamster ovary cells (Recombinate) has been evaluated
      through comparisons of the protein produced at the beginning, middle and end of a
      typical production campaign. METHODS: Recombinant human factor VIII was incubated
      with thrombin, the resulting four polypeptides were isolated by RP-HPLC,
      subjected to proteolysis with trypsin, and the peptide mixtures were resolved by
      RP-HPLC. Tryptic peptide mixtures were subjected to online mass spectrometric
      analysis using an electrospray ionization source interfaced to a quadrupole mass
      analyzer scanning from 1950-200 amu, and the peptide ion data were compared for
      three lots produced from the beginning, middle and end of a production campaign.
      RESULTS: The UV elution profiles for each of the rhFVIIIa polypeptides were
      highly similar for factor VIII isolated from the beginning, middle and end of
      production. Total ion data from the peptide maps derived from three lots of
      rhFVIII were compared by MH1+ values as a function of scan range. A total of 918
      ions were analyzed for the four polypeptides of rhFVIII produced at the
      beginning, middle and end of a production campaign. The ions were detected at the
      same relative retention times, as indicated by the similar scan numbers for the
      three lots. CONCLUSIONS: These observations support that rhFVIII preparations
      produced from the beginning, middle and end of a production campaign were highly
      similar, and demonstrate genetic stability in the manufacturing process of
      Recombinate.

PMID- 9279897
TI  - The epidemiology of BSE in cattle herds in Great Britain. I. Epidemiological
      processes, demography of cattle and approaches to control by culling.
AB  - This paper explores the key epidemiological processes and demographic factors
      that determined the pattern of transmission of the aetiological agent of bovine
      spongiform encephalopathy (BSE) in cattle herds in Great Britain (GB). The
      analyses presented utilize data from published and unpublished experimental
      studies and from the GB central database of confirmed BSE cases. We review the
      experimental and epidemiological evidence that has both confirmed indirect
      horizontal transmission via the consumption of infectious material as the major
      transmission route and provided information on the duration and variability of
      the dose-dependent incubation period of BSE in cattle. The epidemiological and
      genetic data pertaining to the possible existence of maternal transmission and/or
      genetically variable susceptibility to infection is discussed. The demography of
      British cattle is characterized and the impacts of key demographic features on
      the observed epidemic profile are discussed. In the main BSE case database,
      analyses reveal that BSE cases cluster significantly at both the holding and
      county scale. Furthermore, analysis of longitudinal patterns reveal substantial
      temporal within-holding correlation. Such clustering of cases suggests a highly
      heterogeneous infection process. The paper ends with a discussion of how analyses
      of spatio-temporal clustering inform the design of targeted culling programmes
      aimed at reducing future disease incidence. We show how the retrospective
      implementation of culling policies on the BSE case database allows the
      qualitative evaluation of policy performance, but that model predictions of
      future trends in case incidence are required to estimate the precise impact of
      any current or future programme.

PMID- 9279898
TI  - The epidemiology of BSE in cattle herds in Great Britain. II. Model construction
      and analysis of transmission dynamics.
AB  - Mathematical model that describe the key processes determining the pattern of the
      bovine spongiform encephalopathy (BSE) epidemic in British cattle are derived
      that allow for infection from feed as well as maternal and direct horizontal
      transmission. Heterogeneous susceptibility classes are also incorporated into the
      analysis. Maximum likelihood methods are used to estimate parameters and to
      obtain confidence intervals from available experimental and epidemiological data.
      A comprehensive sensitivity analysis of all model parameters and distributional
      assumptions is presented. Additional validation is provided by fitting the model
      to independent data collected in Northern Ireland. Model estimates and
      predictions based on BSE case data for Great Britain and Northern Ireland,
      together with their implications, are reviewed, and future research priorities
      discussed.

PMID- 9279899
TI  - Density-dependent selection on horn phenotype in Soay sheep.
AB  - In the naturally regulated population of Soay sheep (Ovis aries L.) on Hirta (St
      Kilda), 12% of males and 24% of females have scurred horns. This trait reduces
      the competitive ability of males in the mating season but is associated with
      higher overwinter survival rates in both sexes (Moorcroft et al. 1996). In this
      paper, we show that scurred females also show higher conception rates and weaning
      rates than non-scurred ones, and that these differences are associated with
      heavier maternal body weight as well as higher birth weights of offspring.
      Selection pressures favouring scurredness in females vary with population density
      and are generally more pronounced among younger animals than adults. We discuss
      these results with reference to recent suggestions that temporal fluctuation in
      selection pressures may help to maintain genetic diversity within populations. We
      suggest that selection against scurredness operating through male mating success
      is opposed by selection favouring this trait, operating through the breeding
      success of females and the survival of both sexes.

PMID- 9279900
TI  - A technique for the fast calculation of three-dimensional photon dose
      distributions using the superposition model.
AB  - Techniques for reducing computation time in 3D photon dose calculations are
      addressed with specific emphasis given to the convolution/superposition approach.
      A single polyenergetic superposition model calculating absorbed dose per incident
      photon fluence (Gy cm2) was developed in terms of TERMA and a total energy
      deposition kernel (a total point spread function). A novel approach was devised
      for reducing calculation time. The method, named the CF method, was based on the
      use of a conventional, fast model (here a modified power-law method was used) for
      the generation of 3D dose distributions on a fine dose matrix. Superposition
      calculations were carried out on a coarse matrix and calculation speed was
      increased simply by reducing the number of calculations. A set of correction
      factors was derived on the coarse grid from the ratio of the dose values from
      superposition to those from the conventional algorithm. These were interpolated
      onto the fine matrix and used to modify the dose calculation from the
      conventional algorithm. The method was tested in a worst-case example where large
      dose gradients were present and in a clinically relevant irradiation geometry. It
      is shown that the time required for the generation of a 3D matrix with
      superposition can be reduced by at least a factor of 100 with no significant loss
      in accuracy.

PMID- 9279901
TI  - Calculated energy response correction factors for LiF thermoluminescent
      dosemeters employed in the seventh EULEP dosimetry intercomparison.
AB  - Several dosimetry intercomparisons for whole body irradiation of mice have been
      organized by the European Late Effects Project Group (EULEP). These studies were
      performed employing a mouse phantom loaded with LiF thermoluminescent dosemeters
      (TLDs). In-phantom, the energy response of the LiF TLDs differs from free-in-air,
      due to spectral differences caused by attenuation and scatter of x-rays. From
      previous studies, energy response correction factors in-phantom relative to free
      in-air were available for full scatter conditions. In the more recent
      intercomparisons, however, full scatter conditions were not always employed by
      the participants. Therefore, Monte Carlo calculations of radiation transport were
      performed to verify the LiF TLD energy response correction factors in-phantom
      relative to free-in-air for full scatter conditions and to obtain energy response
      correction factors for geometries where full scatter conditions are not met. For
      incident x-rays with HVLs in the 1 to 3.5 mm Cu range, the energy response
      correction factor in-phantom deviates by 2 to 4 per cent from that measured free
      in-air. This is in reasonable agreement with previously published results. The
      energy response correction factors obtained from the present study refer to a
      calibration in terms of muscle tissue dose in-phantom using 60Co gamma rays. For
      geometries where full scatter conditions are not fulfilled, the energy response
      correction factors are different by up to about 3 per cent at maximum from that
      at full scatter conditions. The dependence of the energy response correction
      factor as a function of the position in-phantom is small, i.e. about 1 per cent
      at maximum between central and top or bottom positions.

PMID- 9279902
TI  - Practical approach to electron beam dosimetry at extended SSD.
AB  - This paper presents a practical approach to clinical dosimetry for electron beams
      at extended source-to-surface distance (SSD). Characteristics of electron beams
      from a Siemens MD-2 accelerator are presented at a nominal SSD of 100 cm and an
      extended SSD of 115 cm. Relative output factors are measured at both 100 and 115
      cm SSDs for a range of square field sizes for each beam energy. The change of
      output with SSD does not follow the inverse square law, if the nominal SSD is
      used. This deviation is larger for lower beam energy and smaller field sizes. An
      effective SSD, SSDeff, has been determined at dmax for each beam energy as a
      function of field size. A comprehensive approach to treatment time calculations
      is proposed.

PMID- 9279903
TI  - Tests of the geometrical description of blood vessels in a thermal model using
      counter-current geometries.
AB  - We have developed a thermal model, for use in hyperthermia treatment planning, in
      which blood vessels are described as geometrical objects; 3D curves with
      associated diameters. For the calculation of the heat exchange with the tissue an
      analytic result is used. To arrive at this result some assumptions were made. One
      of these assumptions is a cylindrically symmetric temperature distribution. In
      this paper the behaviour of the model is examined for counter-current vessel
      geometries for which this assumption is not valid. Counter-current vessel pairs
      intersecting a circular tissue slice are tested. For these 2D geometries vessel
      spacing, tissue radius and resolution are varied, as well as the position of the
      vessel pair with respect to the discretized tissue grid. The simulation results
      are evaluated by comparison of the different heat flow rates with analytical
      predictions. The tests show that for a fixed vessel configuration the accuracy is
      not a simple decreasing function of the voxel dimensions, but is also sensitive
      to the position of the configuration with respect to the discretized tissue grid.

PMID- 9279904
TI  - Visibility of microcalcifications in computed and screen-film mammography.
AB  - Due to the clinically and technically demanding nature of breast x-ray imaging,
      mammography still remains one of the few essentially film-based radiological
      imaging techniques in modern medical imaging. There are a range of possible
      benefits available if a practical and economical direct digital imaging technique
      can be introduced to routine clinical practice. There has been much debate
      regarding the minimum specification required for direct digital acquisition. One
      such direct digital system available is computed radiography (CR), which has a
      modest specification when compared with modern screen-film mammography (SFM)
      systems. This paper details two psychophysical studies in which the detection of
      simulated microcalcifications with CR has been directly compared to that with
      SFM. The first study found that under scatter-free conditions the minimum
      detectable size of microcalcification was approximately 130 microns for both SFM
      and CR. The second study found that SFM had a 4.6% higher probability of
      observers being able to correctly identify the shape of 350 microns diameter test
      details; there was no significant difference for-either larger or smaller test
      details. From the results of these studies it has been demonstrated that the
      modest specification of CR, in terms of limiting resolution, does not translate
      into a dramatic difference in the perception of details at the limit of
      detectability. When judging the imaging performance of a system it is more
      important to compare the signal-to-noise ratio transfer spectrum characteristics,
      rather than simply the modulation transfer function.

PMID- 9279905
TI  - Assessment of stenosis severity using a novel method to estimate spatial and
      temporal variations of blood flow velocity in biplane coronarography.
AB  - The authors present a novel method to estimate absolute blood flow velocity in
      coronary arteries from biplane angiograms. Spatial and temporal velocity
      variations are derived giving simultaneously a direct geometric and an indirect
      functional index of stenosis severity, stenosis ratio and coronary flow reserve.
      No prior assumption concerning stenosis geometry is made. Deformable models are
      used to track a coronary artery segment dynamically in three dimensions. A
      densitometric map is obtained by summing densities across sections at every
      position along the previously calculated path and at every time of the cardiac
      cycle. An advection relationship between density and velocity is observed. The
      spatiotemporal velocity map is a solution of a nonlinear least-squares scheme. A
      simulation protocol based on simple geometric conformations and blood flow
      properties is used to assess numerical stability and immunity towards noise.
      Predicted results for temporal velocity variations are compared with the
      intracoronary Doppler recordings to test the model assumptions for basal state
      and hyperaemia examinations of the same patient. The stenosis ratio was accurate
      to within 3% for a simulated additive Gaussian noise with a standard deviation of
      0.14. The limits of agreement between angiographic and Doppler velocities were 
      11.4 and 11.8 cm s-1 for a peak value of 23 cm s-1 (basal state) and -16.8 and
      13.5 cm s-1 for a peak value of 52 cm s-1 (hyperaemia), corresponding to 18 and
      3.5% errors on the average peak values and a 16% error on the coronary flow
      reserve. To summarize, the advection model derivation and its solution are
      presented. Simulated and experimental results corroborate the validity of the
      numerical schemes and support clinical applicability.

PMID- 9279906
TI  - A linear array silicon pixel detector: images of a mammographic test object and
      evaluation of delivered doses.
AB  - We present images of a mammographic test object obtained using a linear array
      silicon pixel detector capable of single-photon counting. The detector pixel size
      was 200 x 300 microns2 and images were acquired by scanning the test object
      between the laminar detector and the x-ray source with a scanning step of 100
      microns. A molybdenum anode tube was used with two different filtrations: 2 mm
      aluminium and 25 microns molybdenum. Conventional film-screen images were also
      obtained in order to compare spatial and contrast resolution. In our digital
      images it is possible to recognize low-contrast details having dimensions smaller
      than or equal to the dimensions of details visible by means of a clinical
      mammographic unit. The detection of microcalcifications smaller than 150 microns
      was possible only when using the Mo filtration. However a copper wire of 50
      microns diameter was detectable when embedded in a simulated tissue. We discuss
      in detail the mean glandular doses (MGDs) delivered during the image acquisition.
      The MGDs necessary to obtain good-quality images are always smaller than at a
      conventional mammographic unit. Since MGDs depend on the x-ray spectrum, the dose
      reduction becomes larger when the applied spectrum is harder than in film-screen
      acquisition (Al filtration and 35 kVp).

PMID- 9279907
TI  - Measurement of the ferric diffusion coefficient in agarose and gelatine gels by
      utilization of the evolution of a radiation induced edge as reflected in
      relaxation rate images.
AB  - A method has been developed to determine the diffusion coefficients of ferric
      ions in ferrous sulphate doped gels. A radiation induced edge was created in the
      gel, and two spin-echo sequences were used to acquire a pair of images of the gel
      at different points of time. For each of these image pairs, a longitudinal
      relaxation rate image was derived. From profiles through these images, the
      standard deviations of the Gaussian functions that characterize diffusion were
      determined. These data provided the basis for the determination of the ferric
      diffusion coefficients by two different methods. Simulations indicate that the
      use of single spin-echo images in this procedure may in some cases lead to a
      significant underestimation of the diffusion coefficient. The technique was
      applied to different agarose and gelatine gels that were prepared, irradiated and
      imaged simultaneously. The results indicate that the diffusion coefficient is
      lower in a gelatine gel than in an agarose gel. Addition of xylenol orange to a
      gelatine gel lowers the diffusion coefficient from 1.45 to 0.81 mm2 h-1, at the
      cost of significantly lower Rl sensitivity. The addition of benzoic acid to the
      latter gel did not increase the Rl sensitivity.

PMID- 9279908
TI  - Chlorine and sodium perfusion and electrolyte balance in human tissue and tumours
      before and during neutron and photon radiotherapy.
AB  - Radiotherapy with nuclear reactor fission neutrons was applied in 49 cases of
      pretreated patients with superficial metastases or relapses from primary
      carcinoma. Measurements of the decay rates of the radiation-induced radioactivity
      of 49Ca, 38Cl and 24Na in the irradiated tissue resulted in values for the
      simultaneous local kinetics of chlorine and sodium, and in approximate data on
      the electrolyte masses. The electrolytes were present in non-exchangeable and
      exchangeable compartments of soft tissue. Exchange times of the intravascular to
      extravascular turnover and the frequencies of the exchange fractions were
      determined for a series of irradiations. The results have been interpreted in
      terms of the mean electrolyte exchange rates, of a standardized functional blood
      flow, and of the supply capacity of the vascular system. In the average of all
      cases, the regional perfusion was reduced by about 30% by irradiation up to 14 Gy
      (equivalent photon dose = 45 Gy) connected with an increase in the non
      exchangeable fractions. After fractionated doses higher than 14 Gy, functional
      blood flow and supply capacity increased to 120%, and fixed electrolytes were
      removed from the irradiated tissue. Data on electrolyte kinetics and vascularity
      are compared with the literature.

PMID- 9279909
TI  - A proposal for minimum detectable compartment in MIRD dosimetry modelling.
AB  - The accuracy of radiation dose estimates from radiopharmaceutical administrations
      has recently become more important for three main reasons: (i) clinical providers
      are demanding more information on diagnostic procedures; (ii) regulatory groups
      are scrutinizing dosimetry for research subjects; and (iii) accurate organ doses
      are crucial in therapeutic administrations. These dose estimates are a sensitive
      function of the residence times. Because most clinical data acquisition protocols
      are limited to the first 24 h after dose administration, the area under the
      remainder of the time-activity curve (TAC) must be estimated. Estimation methods
      range from assuming physical decay only (overly conservative) to extrapolating
      end point physiological kinetics (overly liberal). This study demonstrates how
      much the results from these two methods vary and develops an alternative method
      which more accurately estimates this remainder term. A method, called the minimum
      detectable compartment (MDC), is constructed so that an accurate dose estimate
      can be made with a realistic measure of the remainder term. The method for
      determining MDC uses standard hypothesis testing. Using an analogue of the
      traditional minimal detectable activity calculation, a model with and without
      constant compartments is fitted to the TAC. The size of the constant compartment
      is varied until the relative likelihood of the two models meets the desired
      measure of power and sensitivity. Computer simulations of a simple mono
      exponential are used to demonstrate the MDC as a function of the model, the
      number of data points, the range of the data and the noise in the data. The MDC
      is a very sensitive function of the data range. It falls by more than 50% when
      the data range is increased from two to three half-lives. In addition, the MDC is
      moderately sensitive to the noise in the data and relatively insensitive to the
      number of data points. These findings suggest that the MDC method can also be
      uses a priori to indicate what type of data collection regimen is necessary to
      achieve a certain accuracy.

PMID- 9279910
TI  - Scatter compensation methods in 3D iterative SPECT reconstruction: a simulation
      study.
AB  - Effects of different scatter compensation methods incorporated in fully 3D
      iterative reconstruction are investigated. The methods are: (i) the inclusion of
      an 'ideal scatter estimate' (ISE); (ii) like (i) but with a noiseless scatter
      estimate (ISE-NF); (iii) incorporation of scatter in the point spread function
      during iterative reconstruction ('ideal scatter model', ISM); (iv) no scatter
      compensation (NSC); (v) ideal scatter rejection (ISR), as can be approximated by
      using a camera with a perfect energy resolution. The iterative method used was an
      ordered subset expectation maximization (OS-EM) algorithm. A cylinder containing
      small cold spheres was used to calculate contrast-to-noise curves. For a brain
      study, global errors between reconstruction and 'true' distributions were
      calculated. Results show that ISR is superior to all other methods. In all cases
      considered, ISM is superior to ISE and performs approximately as well as (brain
      study) or better than (cylinder data) ISE-NF. Both ISM and ISE improve contrast
      to-noise curves and reduce global errors, compared with NSC. In the case of ISE,
      blurring of the scatter estimate with a Gaussian kernel results in slightly
      reduced errors in brain studies, especially at low count levels. The optimal
      Gaussian kernel size is strongly dependent on the noise level.

PMID- 9279911
TI  - An attenuation measurement technique for rotating planar detector positron
      tomographs.
AB  - This paper presents a new attenuation measurement technique suitable for rotating
      planar detector positron tomographs. Transmission measurements are made using two
      unshielded positron-emitting line sources, one attached to the front face of each
      detector. Many of the scattered and accidental coincidences are rejected by
      including only those coincidences that form a vector passing within a
      predetermined distance of either line source. Some scattered and accidental
      coincidences are still included, which reduces the measured linear attenuation:
      in principle their contribution can be accurately estimated and subtracted, but
      in practice, when limited statistics are available (as is the case with the multi
      wire Birmingham positron camera), this background subtraction unacceptably
      increases the noise. Instead an attenuation image having the correct features can
      be reconstructed from the measured projections. For objects containing only a few
      discrete linear attenuation coefficients, segmentation of this attenuation image
      reduces noise and allows the correct linear attenuation coefficients to be
      restored by renormalization. Reprojection through the segmented image may then
      provide quantitatively correct attenuation correction factors of sufficient
      statistical quality to correct for attenuation in PET emission images.

PMID- 9279912
TI  - Improved receptor analysis in PET using a priori information from in vitro
      binding assays.
AB  - An accurate determination of non-specific binding is required for the analysis of
      in vitro and in vivo receptor binding data. For some radioligands the non
      specific binding is of the same magnitude as the specific binding. Furthermore,
      in vitro measurements have shown that the non-specific binding can be different
      in different brain regions. If this is the case in a PET study for determining
      Bmax and Kd, a correction for the non-specific binding has to be applied. The aim
      of the present communication is to present a means for determining corrected Bmax
      and Kd with Scatchard analysis using in vitro binding studies. The influence of
      non-specific binding on the free and specifically bound radioligand is expressed
      with the aid of a correction factor, which can be calculated from measurable
      quantities. Introduction of the corrected free and specifically bound radioligand
      should give binding parameters closer to reality than previously obtained
      results.

PMID- 9279913
TI  - Applications of the Italian protocol for the calibration of brachytherapy
      sources.
AB  - The Associazione Italiana di Fisica Biomedica (AIFB; Italian Association of
      Biomedical Physics) has adopted the Italian protocol for the calibration of
      brachytherapy sources. The AIFB protocol allows measurements of the reference air
      kerma rate, Kr, within 1.7% (1 sigma). To measure Kr the AIFB protocol has
      identified a direct and an indirect procedure. The direct procedure is based on
      the use of spherical or cylindrical ionization chambers as local reference
      dosimeters positioned along the transverse bisector axis of the source. Once the
      source is specified by a Kr value, this can be used to calibrate a field
      instrument, such as a well-type ionization chamber, for further source
      calibrations by means of an indirect procedure. This paper reports the results
      obtained by the Physics Laboratory of the Universita Cattolica del S Cuore (PL
      UCSC), in terms of Kr calibration of five types of source, 169Yb, 192Ir and
      137Cs. The role of the Kr determination for a brachytherapy source has been
      underlined when a new source such as the 169Yb seed model X1267 has been proposed
      for clinical use. The Kr values for 137Cs spherical sources differed by 5% from
      the vendor's mean value. The five types of source calibrated in terms of Kr were
      used to obtain the calibration factor. NKrsource, of an HDR-1000 well-type
      ionization chamber.

PMID- 9279914
TI  - Comments on 'dielectric properties of the skin'.

PMID- 9279915
TI  - A reply to "comments on 'MTF evaluation of a phosphor-coated CCD for x-ray
      imaging'".

PMID- 9279916
TI  - Effect of growth rate and body mass on resting metabolic rate in galliform
      chicks.
AB  - In this study, we asked whether within-species variation in chick resting
      metabolic rate was related to variation in growth and whether this relationship
      changed during development in three galliform species (turkey, Meleagris
      gallopavo, guinea fowl, Numida meleagris, and Japanese quail, Coturnix coturnix
      japonica). Resting metabolic rate increased by a bi- or triphasic pattern with
      body mass. For each phase, the relationship between metabolic rate and growth was
      studied by residual analysis, with two measures of growth: growth rate and body
      mass. Chick mass reflects the net result of accumulated growth, while hatchling
      mass reflects embryonic growth. In hatchlings, high metabolic rates coincided
      with low growth rates in turkeys and guinea fowl. These species delay initial
      food intake, and under these circumstances high metabolic expenditure may
      preclude conversion of yolk energy into body mass. No relationship was present
      between residual hatching metabolic rate and residual body mass. In older chicks,
      residual metabolic rate was positively linearly related with residual growth rate
      (turkeys and young quail) or residual body mass (guinea fowl and older quail).
      The similarity of the slopes suggests that growth rate and accumulated growth
      affected maintenance metabolism to the same extent throughout development. These
      findings suggest that growth models must take ontogenetic adjustments of
      metabolic rate into account in addition to costs of maintenance.

PMID- 9279917
TI  - Growth rate and maturation of skeletal muscles over a size range of galliform
      birds.
AB  - The relationship between growth rate and development of function in leg and
      pectoral muscles was studied in four species of galliform birds ranging from 125
      g to 18 kg and, for comparison, in an altricial species, the European starling
      (80 g). An index to neonatal maturity (muscle dry content proportion as a
      fraction of adult value) was higher in leg than in pectoral muscles and lower in
      larger than in smaller galliforms. The maturity index was substantially lower in
      starling neonates. After the first week posthatch, however, the maturity index
      was highest in larger species. Exponential growth rates decreased linearly with
      increasing maturity in both pectoral and leg muscles, following similar
      regressions in all species including the starling. At a particular value of the
      maturity index, the exponential growth rate was higher in pectoral than in leg
      muscles. The exponential growth rates of muscles of neonatal large galliforms
      were lower than expected from their low maturity. This may represent the down
      regulation shortly after hatching of the high exponential growth rate needed to
      reach a large hatching mass in a short incubation period. A slower growth rate
      immediately posthatch may be necessary if the relatively immature neonatal
      digestive system cannot deliver nutrients or metabolized energy required for more
      rapid growth. Smaller species may not be faced with the constraint of rapid
      growth toward the end of the embryonic period.

PMID- 9279918
TI  - Influence of environmental salinity on routine metabolic rate and critical oxygen
      tension of Cyprinodon variegatus.
AB  - We examined the influence of a wide range of environmental salinities on routine
      metabolic rate and critical oxygen tension in Cyprinodon variegatus, a common
      coastal resident of the western Atlantic Ocean and Gulf of Mexico. C. variegatus
      lives in ambient salinities ranging from freshwater to 142/1000, with fish used
      in this study obtained from a Gulf of Mexico salt marsh near Cedar Key, Florida.
      In a steady state experiment, routine metabolic rate and critical oxygen tension
      were determined at salinities ranging from 0/1000 to 100/1000. Measures of
      routine metabolic rate and critical oxygen tension were unaffected by changes in
      salinity between 0/1000 and 40/1000. However, routine metabolic rate declined and
      critical oxygen tension increased progressively at salinities above 40/1000. The
      reduction in routine metabolic rate and rise in critical oxygen tension
      correlates with a reduced ability of C. variegatus to osmoregulate effectively at
      high salinities. The variations in routine metabolic rate and critical oxygen
      tension at high salinities suggest that C. variegatus responds to high salinities
      by reducing energy expenditures, effectively increasing the time that individuals
      can tolerate hypersaline conditions.

PMID- 9279920
TI  - Gas permeability of American alligator eggs and its anatomical basis.
AB  - The barrier to gas flux across the eggs of American alligators (Alligator
      mississippiensis) consists of a calcareous shell and an underlying shell membrane
      of two layers, a limiting membrane facing the embryo and a fibrous membrane
      facing the shell. The limiting membrane is penetrated by an immense population
      (averaging 341,188 cm-2) of tiny pores (averaging 0.51 micron in diameter) and a
      small population (averaging 190 cm-2) of large pores (averaging 34.6 microns in
      diameter). An estimated 6% of these pores are open at the onset of incubation,
      and 22%-24% are open near hatch. The shell membrane is 2.6-10 times less
      permeable to O2 than the shell. Its permeability nearly quadruples during
      incubation, is higher at the equator than elsewhere, increases more rapidly when
      eggs are incubated at 33 degrees C as opposed to 30 degrees C, and appears to
      depend primarily on its water content. In contrast, the shell's permeability to
      O2, as well as its water vapor conductance and the number of open pores in it,
      does not change significantly during incubation.

PMID- 9279921
TI  - Sodium economy in white-tailed deer (Odocoileus virginianus).
AB  - Sodium is considered the mineral most limiting to growth and reproduction of
      mammalian herbivores worldwide. Notwithstanding the large database on
      physiological adaptations to low sodium intake, information on maintenance sodium
      requirements and sodium dynamics of mammals is depauperate. We measured sodium
      intake and output in adult, nonreproductive white-tailed deer (n = 15) over four
      seasons to estimate daily requirements for sodium on a seasonal and an annual
      basis. Dietary sodium content was based on best available predictions of sodium
      requirements. With regression techniques, we estimated metabolic fecal excretion
      and endogenous urinary losses of sodium. Average daily sodium requirement,
      defined as the minimum sodium intake at which intake equaled excretion, was
      estimated to be 3.27 mg kg-1 body mass d-1. Seasonal estimates did not vary. We
      propose that sodium requirements for maintenance in mammalian herbivores scale to
      body mass at an exponent that is similar to that for metabolic rate and forage
      intake (0.71-0.75). Development of an allometric relationship between sodium need
      and body mass would permit stronger inference regarding the role of sodium in
      population regulation, foraging decisions, or distribution and movements of
      mammalian herbivores.

PMID- 9279919
TI  - Flight-muscle polymorphism in the cricket Gryllus firmus: muscle characteristics
      and their influence on the evolution of flightlessness.
AB  - Flight muscles of the cricket Gryllus firmus are polymorphic, existing as pink or
      white phenotypes. White muscles are smaller in size, have reduced number and size
      of muscle fibers, and have reduced in vitro enzyme activities and respiration
      rates relative to pink muscles of newly molted, fully winged adults. G. firmus is
      also polymorphic for wing length. All newly molted long-winged adults exhibited
      the pink-muscle phenotype, while most newly molted short-winged adults exhibited
      the white-muscle phenotype, which resulted from arrested muscle growth. As long
      winged adults aged, fully grown pink muscle was transformed into white muscle via
      histolysis. The substantially higher respiration rate of pink muscle likely
      contributes to the elevated whole-organism respiration rate of long-winged
      females, which has been documented previously and which is thought to divert
      nutrients from egg production. Histolyzed white flight muscle from long-winged
      crickets also exhibited significantly elevated respiration rate and enzyme
      activities compared with underdeveloped white muscle from short-winged adults,
      although these differences were not as great as those between pink and white
      muscles. Fecundity was much more elevated in females with white verus pink flight
      muscles than it was in females with short versus long wings. The fitness gain
      resulting from flightlessness has typically been estimated in previous studies by
      comparing enhanced egg production of short-winged and long-winged females,
      without considering the influence of flight-muscle variation. Our results suggest
      that the magnitude of this fitness gain has been substantially underestimated.

PMID- 9279922
TI  - Effects of arousal from hibernation and plasma androgen levels on mating behavior
      in the male big brown bat, Eptesicus fuscus.
AB  - The effects of arousal from hibernation and presence of plasma androgen on the
      expression of mating behavior in male big brown bats (Eptesicus fuscus) were
      tested in a captive population exposed to seminatural conditions in central
      Alabama. In the mild winter of 1994-1995, flight cage temperatures never fell
      below 10 degrees C. Bats were never observed to enter sustained (over 2 d)
      torpor. They were also never observed to mate. Unmanipulated, sham-operated, and
      gonadectomized males and unmanipulated females were exposed to 6 d of 4 degrees
      C. All individuals appeared torpid, and body temperatures of monitored bats fell
      at least 15 degrees-20 degrees C. Plasma androgen levels of torpid unmanipulated,
      sham-operated, and gonadectomized males averaged 25.4 +/- 9.2, 19.7 +/- 9.1, and
      1.5 +/- 0.25 ng/mL, respectively, and did not differ significantly from levels
      for the same groups 1 mo previous to induced torpor. When animals were returned
      to 23 degrees C, 57% of unmanipulated, 40% of the sham-operated, and 33% of
      gonadectomized males displayed mating behavior upon arousal. Almost all matings
      occurred within 48 h of arousal, the majority in the first 3 h. Males not exposed
      to low temperatures were not observed to mate. Although individuals from all
      three treatments mated, gonadectomized males averaged fewer mounts and
      copulations per individual. Androgen levels declined significantly from torpor
      levels in all groups 48 h after arousal. Thus, an extended period of low body
      temperature and arousal appeared to be a short-term activator of sexual behavior
      in the big brown bat; unmanipulated males were more strongly affected by this
      stimulus than gonadectomized males.

PMID- 9279923
TI  - Epidermal proteinases in the European eel.
AB  - A fluorescent-sensitive assay demonstrated the exhaustive detection of proteinase
      activities in the dorsal skin of the European eel. Two distinct skin extracts
      were prepared from skin mucus and epidermal cell layers with no mutual
      contamination, so that the latter extract contained significant susceptibility of
      all tested substrates. Optimum hydrolysis pH's for susceptible substrates were
      found in acidic and neutral ranges, and optimum hydrolysis temperatures for the
      same substrates fell mainly in the 40 degrees-50 degrees C range. In addition,
      diverse inhibitory influences on these hydrolyses were prompted by several
      proteinase inhibitors and metal chlorides, and some other reagents specifically
      affected the individual hydrolysis; among them, the inhibitions of all activities
      by p-tosyl-L-phenylalanyl-chloromethylketone CdCl2, CuCl2, HgCl2, and ZnCl2 were
      remarkable. Antipain, iodoacetamide, and CoCl2 induced a severe inhibition of all
      except three activities, whereas N-ethylmaleimide markedly inhibited only these
      three activities. These findings suggest that epidermal cell layers of the
      European eel retain a party of proteolytic enzymes, and this party is judged from
      their exhibiting specificities to be composed of four distinct proteinases,
      presumably cathepsins L and B, a serine proteinase, and an aminopeptidase.

PMID- 9279924
TI  - Inefficiency of lactation in primiparous rats: the costs of first reproduction.
AB  - To investigate the energetic costs of lactation in a female mammal in relation to
      previous reproductive history, we compared the performance of adult female Long
      Evans rats that had previously bred (multiparous) with young females that had not
      previously given birth (primiparous). All litters were standardized to 10 +/- 1
      young. We compared maternal production (growth of pups), body mass, and energy
      intake (food consumption) of mothers, as well as their energy expenditure
      (resting oxygen consumption). The mass of litters at birth and the growth of pups
      during lactation did not differ according to reproductive history of the mothers.
      The body mass of primiparous mothers was less than that of multiparous mothers,
      and primiparous mothers showed an increase in mass during early lactation. To
      accomplish the essentially identical production of offspring under these
      circumstances, the primiparous mothers consumed and expended more energy than the
      multiparous mothers. This remarkable performance of first-time mothers results in
      an overall efficiency of energy allocation to reproduction amounting to only 25%,
      compared with 38% in multiparous mothers. The energetic inefficiency of
      primiparous female lactation results largely from the excessive expenditures
      associated with physiological and behavioral performances of first-time
      reproduction, together with a small component of additional expenditure due to
      further growth by the primiparous mothers. We suggest that this inefficiency
      probably contributes to the observed low reproductive success of novice breeders;
      furthermore, active restraint of fecundity may be an evolutionary response to the
      constraints of the energetic inefficiency of primiparous breeding by female
      mammals.

PMID- 9279925
TI  - Sulfide binding in the body fluids of hydrothermal vent alvinellid polychaetes.
AB  - Dissolved H2S is a major environmental factor in hydrothermal vent ecosystems. In
      a study of adaptations to sulfide by alvinellid polychaetes, the sulfide-binding
      capacity of body fluids was examined in Paralvinella palmiformis from northeast
      Pacific ridges and Alvinella species from the East Pacific Rise. Sulfide
      concentrations in vascular blood and coelomic fluid of freshly collected animals
      were notably variable. Separation of P. palmiformis body-fluid components
      revealed that most sulfide (ca. 77%) was accumulated in the dissolved fraction.
      In P. palmiformis, both vascular blood and coelomic fluid could reversibly bind
      sulfide in vitro with a low affinity, saturating only at high dialysate
      concentrations (ca. 2 mmol L-1). No sulfide-binding activity was observed in the
      vascular blood from Alvinella species. A dissolved protein component of greater
      than 90 kDa appears to be involved in sulfide binding in Paralvinella, probably a
      vascular extracellular high-molecular-weight hemoglobin. Some sulfide may also
      adsorb onto a 15.38-kDa intracellular hemoglobin present in the coelomic
      erythrocyte fraction. In the absence of epibiotic bacteria, Paralvinella body
      fluids may function as a sulfide buffer to protect tissues from deleterious
      effects of sulfide exposure.

PMID- 9279927
TI  - Erik Erikson's clinical contributions. A symposium in memorial tribute.
      Introduction.

PMID- 9279926
TI  - Are precocial young cheaper? Lactation energetics in the guinea pig.
AB  - Caviomorphs stand out from other small rodents by producing extremely precocial
      young. Pups begin to nibble solid food right after birth and can survive weaning
      when 5 d old. We tested whether these properties of young lead to a low cost of
      lactation in guinea pigs (Cavia porcellus). In contrast to altricial rodents,
      energy acquisition and expenditure of guinea pig mothers (litter size, three) was
      highest during the first half of the 23-d lactation period. Daily metabolizable
      energy intake at peak lactation was increased by 126% above nonreproducing level
      and was 65% of the predicted maximal intake. Peak daily energy expenditure was
      1.9 times basal metabolic rate, and resting energy expenditure was elevated 26%
      above nonreproductive level. From the third day, young consumed solid food and
      intake increased linearly over the course of lactation. During lactation, total
      intake of litters through solid food consumption (assuming efficient digestion)
      amounted to 86% of the energy intake that mothers allocated to reproduction
      during that period. The pattern of energy expenditure during lactation in guinea
      pigs differs substantially from that of altricial rodents and is made possible
      because pups contribute through solid food intake. Overall energy demand on the
      mothers is not much lower than in altricial rodents, but lower peak energy demand
      during lactation in guinea pigs may reduce the coupling of reproduction to
      periods of high food abundance.

PMID- 9279928
TI  - The legacy of Erik Homburger Erikson.

PMID- 9279929
TI  - Contributions of Erik Erikson.

PMID- 9279930
TI  - Erik Erikson's work: clinical implications and applications.

PMID- 9279931
TI  - Beauty and the beast: a myth of sadness, madness, and hope in anaclitic
      depression.

PMID- 9279932
TI  - Collective will: a reformulation of Otto Rank's theory of personality
      individuation.
AB  - A reevaluation of Otto Rank's theory of personality individuation has been
      proposed which equates collective and individual will as essential and mutually
      facilitative aspects of self-development. Rank's viewpoint regarding social and
      moral development as necessarily normative and, hence, inimical to individuation
      is therefore challenged and disputed. It is further argued that the nature of
      will is not a priori moral and that it should be conceptualized empirically as a
      derivative of the self. The negative will has been defined as the counterposition
      of two wills against each other. It has been proposed that when the individual
      and collective will are in fixed opposition to each other their results can be
      destructive to personality development and to interpersonal and societal
      relations in general. The relative value given to either individual or collective
      aspects of will may be partly a function of the historical and sociopolitical
      environment of both the individuals whose personality development is thereby
      influenced and the theorist whose interest is devoted to understanding and
      remedying their problems.

PMID- 9279933
TI  - The search for the authentic self.

PMID- 9279934
TI  - Arthur Miller's drama from the standpoint of self psychology.

PMID- 9279935
TI  - Audience as analyst: Dennis Potter's The Singing Detective.
AB  - Author Dennis Potter has written an exceptional psychoanalytically informed
      television series in The Singing Detective. Potter succeeds by echewing the usual
      portrayal of psychoanalysis in cinema and television as a therapy which the
      viewer observes but instead creates, by means of the content and structure of the
      series, a production that forces the audience into a role of analyst. The story
      of the current life and the childhood of the protagonist, Philip Marlow, has
      depth and context which allows the audience to examine the personality of Marlow,
      including character pathology and traits, sexuality, fantasy, dreams, and
      delusions from several metapsychological viewpoints. Potter allows the audience
      to use the dynamic, genetic, topographic, and, most unusual in drama, structural
      viewpoints. The audience can experience aspects of an analyst's experience,
      including the process of formulating and evaluating over time analytic hypotheses
      and coping with emotional reactions to the material which at times has
      transferencelike qualities.

PMID- 9279936
TI  - Physiological and behavioral effects of chronic intracerebroventricular infusion
      of corticotropin-releasing factor in the rat.
AB  - The present study was conducted to investigate the long-term effects of chronic
      elevation of centrally circulating levels of corticotropin-releasing factor (CRF)
      on behavior and physiology. For this purpose ovine CRF was infused continuously
      for a period of 10 days into the lateral ventricle of rats with the aid of
      osmotic pumps (calculated CRF delivery was 4.9 micrograms/day). Changes in daily
      rhythms in body temperature and home cage motor activity were recorded
      telemetrically during the infusion period. The most prominent physiological
      findings were a delayed body weight gain and a long-lasting hyperthermia
      following CRF infusion. The peptide treatment furthermore increased adrenal
      weight and suppressed the weight of the thymus at the end of the experiment.
      Behaviorally, CRF administration elicited a short-lasting increase in activity
      during the light phase and an increased anxiety in an elevated plus-maze 1 week
      after the start of infusion. The similarities between the present results and the
      long-term changes previously described in behaviorally stressed rats indicate
      that chronically elevated levels of CRF in the brain might play an important role
      in the induction and persistence of stress-related behavioral and physiological
      disorders.

PMID- 9279937
TI  - Cytokine secretion in squirrel monkeys.
AB  - The squirrel monkey, a non-human New World primate, has several endocrine
      peculiarities, including a 10-fold higher plasma cortisol concentration than Old
      World primates, such as man. Glucocorticoids are known to have immunomodulatory
      properties. We therefore measured cytokine levels in supernatants of in vitro
      cultures of mononuclear cells from the peripheral blood of squirrel monkeys and
      humans. We stimulated monocytes and lymphocytes with lipopolysaccharide (LPS) and
      phytohemagglutinin (PHA) in the presence or absence of hydrocortisone. Squirrel
      monkey monocytes secreted a more than 100-fold lower level of interleukin-1 beta
      (IL-1 beta) but a four-fold higher level of transforming growth factor beta (TGF
      beta) than human monocytes, whereas the secretion of other cytokines, such as
      tumor necrosis factor alpha (TNF-alpha), TNF-beta and interleukin 2 (IL-2), did
      not differ between squirrel monkeys and humans. However, in squirrel monkey
      lymphocytes, the PHA-stimulated secretion of TNF-alpha was much greater than that
      of TNF-beta. Our results support the view that in squirrel monkeys there are
      subtle adaptations in some immune functions, particularly linked to the
      hypothalamic-pituitary-adrenal (HPA) system rather than a global suppression of
      the immune system.

PMID- 9279938
TI  - Lack of ovarian steroid hormone regulation of norepinephrine transporter mRNA
      expression in the non-human primate locus coeruleus.
AB  - Decreases in ovarian steroids can negatively affect mood, and drugs which block
      the norepinephrine transporter (NET) or the serotonin transporter (SERT)
      alleviate depression. However, the respective contribution of the noradrenergic
      and serotonergic systems may vary depending upon the etiology of the depression.
      We previously demonstrated that E and P alter gene expression for tryptophan
      hydroxylase (TPH) and for the serotonin reuptake transporter (SERT) in raphe
      neurons of the rhesus monkey. In this study, we questioned whether the
      noradrenergic system contributes to depression related to the reproductive
      function in women, using a non-human primate model of the menstrual cycle. The
      effect of estrogen (E) or E plus progesterone (P) on the expression of the NET
      gene in the locus coeruleus (LC) was examined with in situ hybridization for NET
      mRNA. In addition, we questioned whether the neurons of the LC contain nuclear E
      or P receptors (ER/PR). Hence, immunocytochemistry for ER and PR were performed
      on adjacent sections. Treatment groups consisted of monkeys (n = 4 per treatment)
      which were ovariectomized/hysterectomized (spayed), E-treated (28 days) and E+P
      treated (14 days E, +14 days E+P). Expression of mRNA for NET was unchanged at
      any level of the LC due to steroid treatment (p > .05). Neither ER nor PR were
      detected in the LC of any treatment group. Therefore, E and P in a treatment
      paradigm which mimics the menstrual cycle do not directly regulate NET mRNA
      expression in the non-human primate LC. In addition, the noradrenergic neurons of
      the primate LC lack nuclear receptors for ovarian steroids. These data suggest
      that the noradrenergic system may not contribute significantly to depression
      related to changes in ovarian hormones.

PMID- 9279939
TI  - Gender but not stimulus parameters influence prolactin response to
      electroconvulsive therapy.
AB  - The post-ictal prolactin (PRL) response represents one of the most consistent
      findings of electroconvulsive therapy (ECT), but correlates variably with the
      gender of the patient, ECT stimulus waveform, dose and electrode placement. Forty
      patients with endogenous depression (29 drug-naive) received either high-energy
      (240 mC) or low-energy (60 mC) bilateral brief-pulse ECT once or three times a
      week. The PRL and growth hormone (GH) levels were estimated using double antibody
      radioimmunoassay. The average post-ECT PRL levels differed significantly from the
      pre-ECT levels, with a seven- to nine-fold increase in PRL at each week of
      treatment. No such difference was observed in the GH levels. All patients showed
      an increase in PRL levels, whereas 42% failed to show an increase in GH levels.
      The delta PRL response (difference between post-ECT and pre-ECT serum hormone
      levels) was not significantly different between the drug-naive and medicated
      patients nor between the high-energy and low-energy groups at first ECT.
      Similarly, no difference was observed between the once-weekly and thrice-weekly
      groups at the third week of ECT. At each week of treatment, the delta PRL was
      significantly higher in females than in males, unlike the GH response.
      Electroencephalographic (EEG) seizure duration did not correlate with either
      delta PRL or delta GH at first ECT and third week ECT. Apart from gender, none of
      the variables, such as age, baseline severity of illness, presence of psychotic
      symptoms, drug-naive status, stimulus dose, seizure duration, seizure strength,
      pattern and symmetry, frequency of ECT and degree of improvement predicted the
      delta PRL response. Neither stimulus energy nor frequency of ECT had a
      significant effect on PRL response. Gender differences in PRL response to ECT
      merit further investigations.

PMID- 9279940
TI  - Diazepam attenuation of restraint stress-induced corticosterone levels is
      enhanced by prior exposure to repeated restraint.
AB  - Prior research has demonstrated that diazepam decreases hypothalamic-pituitary
      adrenal cortex (HPA) axis activity in stressful contexts but, paradoxically, acts
      as a stimulator of basal axis activity. Also, several investigators have reported
      that low doses of diazepam are not effective in reducing stress-induced
      corticosterone (CORT) levels, yet similar doses typically produce anxiolytic
      effects on behavioral measures of fear and anxiety. We have examined the effects
      of diazepam on plasma CORT levels in male Sprague-Dawley rats utilizing a
      repeated restraint paradigm. Consistent with most literature, diazepam
      administered IP (1.5, 3.0, or 6.0 mg/kg) 1 h prior to restraint increased non
      stress, baseline plasma CORT levels in a dose-dependent fashion. During the first
      exposure to the 1 h restraint-stress procedure, CORT levels of diazepam-injected
      rats did not differ from the stress levels of controls except at the 60-min
      stress time point in those subjects receiving 6.0 mg/kg. However, diazepam at all
      three doses was able to attenuate the stress-induced increase in CORT following 5
      days of diazepam+restraint treatment. Using the 3.0 mg/kg dose as a probe, it was
      found that this effect was not dependent on the repeated administration of
      diazepam, but rather on repeated exposure to restraint. These results suggest
      that repeated restraint produces a change in neural sensitivity to
      benzodiazepines.

PMID- 9279941
TI  - A higher rate of hyperandrogenic disorders in female-to-male transsexuals.
AB  - In an effort to elucidate the aetiology of female-to-male transsexualism (FM-TS)
      12 out of an annual sample of 16 untreated female-to-male transsexuals (FMT),
      aged 19 years 7 months (19;7) to 44 years 8 months (44;8) [median age (M) 27;5]
      were assessed by means of sexual-medical questionnaires, physical and
      endocrinological examination. The control group consisted of 15 healthy women
      (CF), aged 19 years 2 months (19;2) to 36 years 1 month (36;1) (M 22;7) without
      gender identity disorder, who were not under hormonal medication (including
      contraceptives). Baseline levels of testosterone (T; ng/dl), androstenedione (A4;
      ng/dl), dehydroepiandrosterone sulfate (DHEAS; ng/ml), luteinizing hormone (LH;
      IU/l), follicle stimulating hormone (FSH; IU/l), and sex-hormone binding
      globuline (SHBG; microgram/dl) were measured. A standard single-dose ACTH
      stimulation test (250 micrograms ACTH IV; Synacthen) was performed with all
      subjects. Aldosterone (ALDO), corticosterone (B), deoxycorticosterone (DOC),
      progesterone (PROG), 17-hydroxyprogesterone (17OHP), 11-deoxycortisol (S),
      cortisol (F), cortisone (E), pregnenolone (PREG) and 17-hydroxypregnenolone
      (OHPREG) were assessed before and 60 min after ACTH stimulation. Transvaginal
      ultrasound was performed in nine out of 12 FMT (20;11 to 44;8, M 27;5; m 29.1 +/-
      7.5) but not in CF. Results showed that 10 FMT (83.3%) and five CF (33.3%) were
      above normal values for at least one of the measured androgens. Baseline levels
      of T and A4 were significantly higher in FMT than in CF (T: 54.0 +/- 13.8 vs.
      41.1 +/- 12.8; A4: 244.8 +/- 73.0 vs. 190.5 +/- 49.3; p < .05), whereas DHEAS,
      SHBG, LH and FSH did not differ between the groups. Unbound T (T/SHBG ratio) was
      higher in FMT (72.0 +/- 67.6) than in CF (26.4 +/- 15.1). Baseline levels of
      17OHP, OHPREG and DOC were higher in FMT than in CF (p < .05). After ACTH
      stimulation 17OHP and OHPREG remained higher in FMT than in CF (p < .05). Single
      case analysis of ACTH stimulation test together with physical examination
      revealed symptoms for non-classical congenital adrenal hyperplasia (NC-CAH) in
      six FMT (50%) and two CF (13.3%). Eight out of nine FMT who were assessed by
      means of transvaginal ultrasound (i.e. 88.9%; 50.0% of 16) had polycystic ovaries
      (PCO). Oligomenorrhoea or menstrual dysregularities (81.7% of 16 FMT vs. 0% of
      CF), hirsutism (56.2% of 16 FMT vs. 13.3% of 15 CF) and adiposity (25.0% vs. 0%)
      were frequent in FMT, but not in CF. Hyperandrogenism with polycystic ovarian
      syndrome (PCOS) and adrenocortical hyperresponsiveness to ACTH seems to be a
      common finding in FMT. This offers support for a hormonal factor in the genesis
      of FM-TS. Because the prevalence of PCOS and NC-CAH in the female population is
      higher than FM-TS, the true nature of this factor and its interaction with
      environmental influences remains unknown.

PMID- 9279942
TI  - Severe ocular trauma managed with primary pars plana vitrectomy and silicone oil.
AB  - PURPOSE: This study evaluated the outcome of severely injured eyes treated with
      early primary vitrectomy with silicone oil filling. METHODS: A total of 435 eye
      injuries, which required surgical intervention, were reviewed retrospectively. In
      13 eyes (3%) pars plana vitrectomy and silicone oil filling were performed as
      primary surgical repair. Silicone oil filling was restricted to cases with
      laceration of the retina larger than 4 disc diameters (nine eyes), primary
      retinal detachment larger than two quadrants (two eyes) and/or persistent
      intrasurgical hemorrhage (12 eyes). All patients underwent surgery within 24
      hours. RESULTS: After a mean follow-up period of 28.7 months (range, 9-70
      months), 11 eyes achieved a visual acuity ranging from 20/25 to 20/200. Silicone
      oil was removed in 11 of 13 eyes after 5.8 +/- 4.6 months. Recurrent
      proliferative vitreoretinopathy developed in two eyes. CONCLUSIONS: Silicone oil
      tamponade after early primary pars plana vitrectomy may be an alternative for
      primary repair after trauma, especially in severely injured eyes with retinal
      lacerations larger than 4 disc diameters, persistent intrasurgical bleeding,
      and/or primary retinal detachments.

PMID- 9279943
TI  - Choroidal findings in the course of idiopathic serous pigment epithelium
      detachment detected by indocyanine green videoangiography.
AB  - PURPOSE: To analyze the choroidal alterations associated with idiopathic serous
      pigment epithelium detachment. METHODS: Twenty-five consecutive patients affected
      by idiopathic serous pigment epithelium detachment underwent ophthalmoscopy,
      fluorescein angiography, and indocyanine green videoangiography. RESULTS: On
      indocyanine green videoangiography an early, complete, and homogeneous filling of
      the pigment epithelium detachment was always observed. In the late phases, the
      indocyanine green pattern depended on the size of the detachment. An idiopathic
      serous pigment epithelium detachment larger than the diameter of one optic disk
      was still hyperfluorescent in the late phases of indocyanine green
      videoangiography and was surrounded by a ring of brighter hyperfluorescence. An
      idiopathic serous pigment epithelium detachment smaller than the diameter of one
      optic disk usually could be visualized in the late phases as a hypofluorescent
      area surrounded by a hyperfluorescent ring. In 30 eyes (83.3%), choroidal
      hyperpermeability was observed. An irregular dilatation of the choroidal veins at
      the site or within an area the size of one disk diameter from the detachments
      could be visualized on indocyanine green videoangiography in 12 of 36 affected
      eyes (33.3%); in three cases an active focus of central serous chorioretinopathy
      with subretinal leakage developed in the follow-up period. CONCLUSION: The
      observation that pigment epithelium detachments frequently are associated with
      choroidal leakage and venous dilatation supports the hypothesis that an
      idiopathic serous pigment epithelium detachment is a variant of central serous
      chorioretinopathy. Moreover, the choroidal permeability alterations detected by
      indocyanine green videoangiography would support the theory of Gass that
      idiopathic serous pigment epithelium detachments could be caused by exudation of
      fluids from the choroidal vessels.

PMID- 9279944
TI  - Autosomal dominant vitreoretinochoroidopathy.
AB  - BACKGROUND: Autosomal dominant vitreoretinochoroidopathy recently has been
      described as a condition characterized by peripheral chorioretinal atrophy and
      areas of hypopigmentation and hyperpigmentation between the equator and the ora
      serrata circumferentially in the ocular fundus. We describe the clinical features
      of a family, some members of which have this disorder. This is the first such
      report of a family outside the United States. METHODS: We examined a family of 15
      individuals, seven of whom were affected. RESULTS: The main clinical findings
      were peripheral pigmentary changes for 360 degrees, with a discrete boundary near
      the equator. In one patient, a partial vitreous detachment was found that was
      creating increasing traction to the macula and to the peripheral retina. Vitreous
      surgery successfully relieved the traction, and vision recovered from 20/100 to
      20/25. One patient lost visual acuity at the age of 10 years when complete
      rhegmatogenous detachment occurred. In two women, a horizontal nystagmus was
      present showing typical signs of a congenital nystagmus. Results of
      electrooculography demonstrated a marked reduction of light rise and a clear
      reduced Arden ratio in one patient. CONCLUSIONS: Autosomal dominant
      vitreoretinochoroidopathy appears clinically as mainly a peripheral tapetoretinal
      disease; patients with this disease have been reported in and outside the United
      States. In addition to the typical peripheral features, significant vitreous
      traction maculopathy and congenital nystagmus associated with the disease were
      found.

PMID- 9279945
TI  - Scanning laser ophthalmoscopy in the early diagnosis of vitreoretinal interface
      syndrome.
AB  - BACKGROUND: The purpose of this study was to estimate if and to what extent
      scanning laser ophthalmoscopy can help in the early diagnosis and follow-up
      management of the vitreoretinal interface syndrome, which includes disorders such
      as cellophane maculopathy, pseudomacular hole, macular pucker, and macular hole.
      METHODS: The 35 fellow eyes of 35 patients with vitreoretinal interface syndromes
      in the first eye underwent scanning laser ophthalmoscopy microperimetry and
      argon, helium-neon, and infrared scanning laser ophthalmoscopy. Fellow eyes were
      defined as clinically positive or negative for vitreoretinal interface syndrome.
      Fellow eyes then were classified based on scanning laser ophthalmoscopy
      techniques. Patients were observed for an average of 18 months (range, 10-26
      months). RESULTS: Thirty-two of the 35 fellow eyes were classified as clinically
      negative, and three of the 35 were classified as clinically positive. Fifteen of
      the 32 clinically negative fellow eyes were redefined as positive on scanning
      laser ophthalmoscopy. None of the clinically positive eyes proved to be negative
      on scanning laser ophthalmoscopy. During the average follow-up period (18
      months), the condition of five of 18 fellow eyes that were positive on scanning
      laser ophthalmoscopy worsened. None of the 17 eyes that were negative on scanning
      laser ophthalmoscopy worsened. CONCLUSION: Scanning laser ophthalmoscopy can
      produce beautifully clear images of structures that are otherwise difficult to
      see and document, such as posterior hyaloid and the inner retinal layers. Despite
      a relatively limited number of cases and the short duration of the follow-up
      period, the present study suggests that scanning laser ophthalmoscopy has good
      sensitivity and specificity for the early diagnosis of vitreoretinal interface
      syndromes.

PMID- 9279946
TI  - Ocular findings in cutis marmorata telangiectatica congenita. Bilateral exudative
      vitreoretinopathy.
AB  - BACKGROUND: Cutis marmorata telangiectatica congenita is a rare, cutaneous,
      reticulated, vascular anomaly characterized by congenital persistent cutis
      marmorata, telangiectasis, and phlebectasis. While systemic abnormalities
      frequently are associated with cutis marmorata telangiectatica congenita,
      ophthalmic abnormalities are quite rare and include congenital glaucoma and
      congenital, bilateral, total retinal detachments with secondary glaucoma.
      METHODS: The authors report a case of bilateral, tractional retinal detachments
      associated with peripheral fibrovascular proliferation simulating familial
      exudative vitreoretinopathy in a female child with cutis marmorata
      telangiectatica congenita. Molecular genetic analysis of the Norrie's disease
      gene was performed. RESULTS: After vitrectomy, the posterior poles of both eyes
      were reattached successfully. No abnormalities of the Norrie's disease gene were
      identified. CONCLUSIONS: Bilateral exudative vitreoretinopathy is a rare
      ophthalmic manifestation associated with cutis marmorata telangiectatica
      congenita.

PMID- 9279948
TI  - Intraocular injection of recombinant hirudin to prevent experimental
      postoperative fibrin.
AB  - PURPOSE: To test the efficacy of a single intraocular injection of various doses
      of recombinant desulphatohirudin variant 1 (Revasc) in a rabbit model after
      lensectomy-vitrectomy surgery. METHODS: Standard fragmatome lensectomies and core
      vitrectomies were performed on Dutch Belted rabbits. In a masked fashion, 17
      control eyes received single intraocular injections of lactated Ringer's
      solution, and the treated eyes, with eight eyes per treatment group, received
      single intraocular injections of hirudin at doses of 0.02 microgram, 2
      micrograms, 10 micrograms, 50 micrograms, or 200 micrograms. RESULTS: Intraocular
      injections of hirudin were effective in preventing postoperative fibrin formation
      at doses of 2 micrograms. There was no notable intraoperative bleeding. With an
      injection of 2.0 micrograms hirudin there was no hemorrhage at any time after
      surgery; with an injection of 200 micrograms hirudin, however, there was notable
      bleeding. CONCLUSION: Hirudin is effective in the prevention of postoperative
      fibrin formation with a single intraocular injection of 2.0 micrograms after
      lensectomy-vitrectomy surgery in the rabbit model. There was no bleeding at the
      effective dose of 2.0 micrograms; at 100 times the effective dose, however, there
      was significant postoperative bleeding.

PMID- 9279947
TI  - Ophthalmomyiasis interna posterior. Report of a case with optic atrophy.
AB  - PURPOSE: The prognosis for patients with ophthalmomyiasis Interna posterior is
      variable. In many patients the larva remains in the eye for years without
      inducing inflammation or loss of vision. Sometimes, however, the migrating larva
      involves the macula and optic nerve and results in permanent visual loss or even
      blindness. METHODS: Our patient presented with sudden painless loss of vision in
      the right eye that was caused by ophthalmomyiasis interna posterior. Hemorrhage
      of the optic nerve head suggested that the fly larva had entered the vitreous
      cavity from the optic nerve head. Subretinal tracts were sequelae of the
      subretinal migration of the organism. Sequential photographs documented the fly
      larva migration into the optic nerve head head from the vitreous cavity. The
      organism was removed by pars plana vitrectomy and retinectomy. RESULTS: In spite
      of the successful removal of the first stage fly larva, the visual acuity
      remained poor because of optic nerve atrophy. CONCLUSION: We suggest early
      removal of fly larvae to prevent damage and visual loss in cases of ocular
      myiasis interna posterior.

PMID- 9279949
TI  - Clinicopathologic correlation of intraretinal microvascular abnormalities.
AB  - PURPOSE: To define the cross-sectional morphology of intraretinal microvascular
      abnormalities, which previously have been described only in terms of trypsin
      digestion. MATERIAL/METHODS: Fourteen vascular lesions of five patients with
      diabetic retinopathy were identified on fundus photographs and/or fluorescein
      angiograms and classified as intraretinal microvascular abnormalities. Eyes of
      these patients were obtained after the patients' deaths. The period between the
      time at which the photographs were taken and that at which enucleation was
      performed was 3-20 months. The duration of autolysis before fixation was 5 hours
      or less. The embedded tissue was evaluated by light and electron microscopy, and
      these findings were correlated with the clinical appearance. RESULTS: The lesions
      consisted of multiple, closely spaced, thin-walled vascular lumina with a caliber
      of 20-70 microns. They were located in the inner retina and surrounded by a wide
      cuff containing randomly oriented collagen fibers. Endothelial cell nuclei were
      numerous. Pericyte degeneration and multiplication of the endothelial and
      pericyte basement membrane had occurred. Endothelial junctions were short, and
      gaping of junctions was not seen. However, occasional fenestrations were present.
      CONCLUSION: The cross-sectional morphology of intraretinal microvascular
      abnormalities is consistent with vascular pathology typical for intraretinal
      diabetic microangiopathy, but also includes features usually seen in new vessels.
      This supports the concept that intraretinal microvascular abnormalities have the
      particular potential for neovascularization.

PMID- 9279950
TI  - The artificial iris diaphragm for vitreoretinal silicone oil surgery.
AB  - BACKGROUND: Silicone keratopathy frequently develops as a complication of
      silicone oil tamponade in the management of severe trauma in eyes with partial or
      complete aniridia. We therefore designed an "open" artificial iris diaphragm to
      prevent silicone oil-endothelial contact. In hypotony, where insufficient
      circulation of aqueous allows silicone in the anterior chamber despite an open
      diaphragm, a new solution became necessary. The "closed" artificial diaphragm was
      developed. METHODS: In this retrospective study, two consecutive series of
      artificial iris diaphragms were compared. Forty-four patients received either an
      open type (20 eyes) or a closed type (24 eyes) and were observed for 409 +/- 421
      days (range, 32-1912). All eyes were aphakic, normotonous, and had a traumatic,
      compromised iris diaphragm or were aphakic and hypotonic as a result of injury,
      proliferative vitreoretinopathy, proliferative diabetic retinopathy, or uveitis,
      with an intact natural iris diaphragm. RESULTS: Silicone oil was retained behind
      the open diaphragm throughout the observation period in 40% of the eyes. Major
      long-term complications were hypotony and fibrous overgrowth. Silicone was
      retained behind the closed diaphragm in 50% of the eyes. CONCLUSION: Because
      proliferative vitreoretinopathy is active for months and multiple surgical
      interventions become necessary to avoid phthisis in eyes with highly pathologic
      changes, longstanding or permanent silicone tamponade is used. The artificial
      diaphragm prevents silicone-corneal contact in approximately 50% of aphakic eyes
      for at least 1 year.

PMID- 9279952
TI  - Diagnostic and therapeutic challenges.

PMID- 9279951
TI  - The effect of retinal cryoapplication on the vitreous.
AB  - PURPOSE: The effect of retinal cryopexy on the vitreous was studied
      morphologically in an animal model. METHODS: The retina and vitreous were frozen
      with single cryolesions on one eye and 24 contiguous cryolesions on the
      contralateral eye in 16 rabbits. The cryoprobe was applied to the sclera from 3
      mm to 6 mm posterior to the limbus at -60 degrees C until ophthalmoscopically
      visible whitening occurred. Two animals were killed on the first day; the third
      day; after 1, 2, and 4 weeks; and after 2, 3, and 6 months after surgery. The
      eyes were enucleated and prepared by the celloidin embedding method. Each 200
      microgram section was examined by light microscopy. Areas of the specimens were
      dissected and studied by scanning and transmission electron microscopy. RESULTS:
      Single cryolesions did not have a significant generalized effect on the vitreous.
      Evidence of local collagen destruction and dispersion of cells was found near the
      area of cryoapplication. Contiguous cryoapplication led primarily to increased
      density in the vitreous and subretinal edema. The vitreoretinal border was
      invaded by mononuclear cells containing pigment granules. Thickened collagen
      fibers were attached to the coagulated retina in a perpendicular manner and
      traversed the whole vitreous body. After 4 weeks the increased vitreous density
      slowly diminished, and preretinal capillaries surrounded by vitreous collagen
      started to proliferate from the vitreoretinal interface. After 6 months central
      vitreous collagen fibers looked normal. In the area of cryoapplication,
      vitreoretinal membrane formation had occurred. CONCLUSION: Single cryolesions
      have no significant effect of the vitreous. Multiple cryolesions lead to
      neovascularization soon after the procedure (1 month) and membrane formation
      later (6 months after the procedure). This supports the concept that the
      extensive use of cryopexy in human retinal surgery could contribute to the
      development of proliferative vitreoretinopathy.

PMID- 9279953
TI  - Choroidal neovascular membrane as a feature of optic nerve glioma.

PMID- 9279954
TI  - White-centered retinal hemorrhages in ocular toxoplasmosis.

PMID- 9279955
TI  - Multiple posttraumatic choroidal ruptures obscured by hemorrhage: imaging with
      indocyanine green angiography.

PMID- 9279956
TI  - Association of ocular toxoplasmosis and thymoma.

PMID- 9279957
TI  - Vitrectomy for macular hole after pneumatic retinopexy.

PMID- 9279958
TI  - An illuminating intraocular magnet for foreign body retrieval.

PMID- 9279959
TI  - Stereoscopic digital fluorescein and indocyanine green videoangiography.

PMID- 9279960
TI  - Front and side fiberoptic illuminator for vitreous surgery.

PMID- 9279961
TI  - Systematic reviews of diagnostic tests--a new challenge for laboratory medicine.

PMID- 9279962
TI  - The accuracy of C-reactive protein in diagnosing acute appendicitis--a meta
      analysis.
AB  - The aim of the study was to review the literature on the accuracy of C-reactive
      protein (CRP) in diagnosing acute appendicitis. All the relevant articles found
      by searching Medline and the Science Citation Index were reviewed. We used
      summary receiver operating characteristic (SROC) curve analysis to describe the
      central tendency of the studies and to assess potential sources of variability.
      We included 22 articles with a total number of 3436 patients. The sensitivity
      ranged from 0.40 to 0.99, and the specificity from 0.27 to 0.90. The cut-off
      values for a positive test varied from 5 to 25 mg l-1. SROC curve analysis showed
      that CRP performed significantly better in acute abdomen populations (11 studies)
      than in populations already selected for appendectomy (11 studies). The
      diagnostic accuracy of CRP tended to be a little inferior to that of total
      leukocyte count (13 studies). CRP is a test of medium accuracy in diagnosing
      acute appendicitis. The formerly distractingly wide range of sensitivity and
      specificity is at least partly due to variations in cut-off values and to
      differences in study populations. However, definitive conclusions on the clinical
      usefulness of the test could not be drawn.

PMID- 9279963
TI  - A mathematical/physiological model of parathyroid hormone secretion in response
      to blood-ionized calcium lowering in vivo.
AB  - The aim of the present study was to test a mathematical model of the biochemical
      processes in the parathyroid glands responsible for the secretion of parathyroid
      hormone resulting from extracellular calcium reduction. A double exponential
      curve described the parathyroid hormone secretion induced by rapid lowering of
      blood-ionized calcium in humans with normal as well as abnormal parathyroid
      tissue. Our data show that it was possible to establish a simple mathematical
      model of the parathyroid hormone response to blood-ionized calcium lowering,
      sufficient to fit experimental data obtained from patients with abnormal and
      normal parathyroid tissue. The fitted parameters showed no significant
      differences between patients with insulin-dependent diabetes mellitus and
      controls. In primary hyperparathyroidism, the parathyroid hormone production and
      steady-state transport across the cell membrane were increased, probably due to
      the larger amount of parathyroid tissue in these patients. These observations
      reveal a striking functional similarity between abnormal and normal parathyroid
      tissue. Furthermore, an apparently linear relationship between the rate of
      parathyroid hormone elimination from the blood plasma and the rate of cellular
      production/secretion was observed. This could be interpreted as an adaptation of
      the parathyroid gland's ability to produce parathyroid hormone depending on the
      average demand from the body.

PMID- 9279964
TI  - 18-Hydroxycortisol and 18-oxocortisol in Cushing's syndrome.
AB  - In patients with primary aldosteronism due to an aldosterone-producing adenoma
      and glucocorticoid-suppressible aldosteronism, 18-hydroxycortisol and 18
      oxocortisol excretions are elevated. Both steroids are synthesized in the
      transitional zone between the zona glomerulosa and zona fasciculata. There are no
      reports concerning production of these steroids in Cushing's syndrome due to
      adrenal adenoma or hyperplasia, as far as we know. We determined the urinary
      excretion and serum concentration of 18-hydroxycortisol and 18-oxocortisol in
      eight patients with Cushing's syndrome (four due to adrenal adenoma, and four due
      to adrenal hyperplasia). Two of the four patients with adrenal adenoma had high
      levels of urinary and serum 18-hydroxycortisol and 18-oxocortisol; on the other
      hand all the patients with adrenal hyperplasia had normal urinary and serum
      levels of both steroids. Patients with high concentrations of 18-hydroxycortisol
      and 18-oxocortisol, however, showed no differences in clinical features, routine
      laboratory findings and hormonal data compared to patients with normal
      concentrations of 18-hydroxycortisol and 18-oxocortisol. Our data suggest that
      some adrenal adenomas causing Cushing's syndrome originate from transitional
      cells.

PMID- 9279965
TI  - Inhibition of serum phospholipase-A2 in acute pancreatitis by pharmacological
      agents in vitro.
AB  - Phospholipase-A2 has been suggested as having a role in the pathophysiology of
      acute pancreatitis. The inhibition of phospholipase-A2 was studied in vitro using
      17 pharmacological agents in the search for a specific therapy for acute
      pancreatitis. The inhibitory effect was tested using an isotopic assay system
      with 2-palmitoyl-(1-14C)-labelled dipalmitoyl phosphatidylcholine as a substrate
      and 10 microliters of serum from patients with acute necrotizing pancreatitis as
      an enzyme source. Among all agents tested, anti-inflammatory drugs inhibited
      enzyme activity most significantly: indomethacin (9.0 x 10(-3) mol l-1) decreased
      the phospholipase-A2 activity to one- tenth. The weak inhibitory effect could
      also be demonstrated using a lower concentration of 2 x 10(-5) mol l-1, which can
      be achieved after intravenous administration of 50 mg of this drug. The other
      drugs inhibited the enzyme activity at concentrations higher than those achieved
      after intravenous injections in clinical use. Diclofenac (3.1 x 10(-2) mol l-1)
      reduced the phospholipase-A2 activity by 93%, ketoprofen (2.0 x 10(-2) mol l-1)
      or chlorpromazine (1.4 x 10(-2) mol l-1) by 90%, tobramycin (1.7 x 10(-2) mol l
      1) by 84%, doxycycline (9.0 x 10(-3) mol l-1) by 61%, dexamethasone (1.7 x 10(-3)
      mol l-1) by 62%, methylprednisolone (3.8 x 10(-2) mol l-1) by 50%, and pindolol
      (1.0 x 10(-4) mol l-1) by 59%. A weak inhibition of phospholipase-A2 activity was
      demonstrated by betamethasone, bupivacaine, digoxin, hydrocortisone, lidocaine,
      metoprolol, propranolol, and vancomycin. Indomethacin proved the most potent of
      the tested agents in inhibiting phospholipase-A2 activity in serum from patients
      with acute pancreatitis and should be further studied in vivo.

PMID- 9279966
TI  - The acute effect of hyperglycaemia on vessel wall properties.
AB  - Arterial distensibility is a marker of functional and structural vessel wall
      properties. A decreased distensibility is an important risk factor for
      cardiovascular disease. In insulin-dependent diabetes mellitus of short duration,
      arterial stiffness has been reported to be increased, decreased or the same as in
      healthy control subjects. The influence of acute hyperglycaemia on arterial
      stiffness is unclear and might be one of the factors responsible for the
      divergent results which have been observed. We investigated arterial
      distensibility locally in the carotid artery during hyper- and normoglycaemia
      using a glucose clamp technique. Eleven healthy normotensive men underwent both a
      hyperglycaemic and a euglycaemic clamp on separate days. Before and after 2 h of
      clamping, arterial diameter (D) and change in arterial diameter during the heart
      cycle (dD) were measured with a non-invasive vessel wall movement detector
      system. Blood pressure (BP), pulse pressure (dP) and heart rate (HR) were
      recorded with a semi-automated device. Distensibility coefficients (DC),
      reflecting the intrinsic vascular wall elasticity, and compliance coefficients
      (CC), reflecting the buffering capacity of the vessel, were calculated from D, dD
      and dP. (DC = 2*dD/ D*dP, CC = pi*dD*D/2*dP). There were no significant
      differences between the hyperglycaemic and the euglycaemic clamp for D, DC and
      CC. These results suggest that an acute systemic hyperglycaemia is not
      responsible for changes in diameter, distensibility and compliance of the carotid
      artery.

PMID- 9279967
TI  - Detection of enteroviral RNA by a new single-step PCR.
AB  - In this study we present a modified diagnostic routine PCR (polymerase chain
      reaction) technique for the detection of specific enteroviral nucleic acid
      sequences in human body fluids, the use of which would reduce the number of false
      positive results, the costs and the concentration of reagents required in PCR.
      Cerebrospinal samples, pharyngeal swabs and faeces were tested. To this end,
      general primers, selected in the highly conserved 5' non-coding region were used,
      with a closed-tube RT semi-nested PCR protocol, and the PCR product was analysed
      using a hybridization in solid phase. A total of 32 patients with suspected
      enteroviral infection, 17 with suspected viral meningitis and 15 with a possible
      acute enteroviral infection different from meningitis were analysed, and 80% of
      the patients with possible acute enteroviral infection were PCR-positive. A broad
      range of enteroviruses can be detected and false-positive results can be reduced.
      The availability of results in less than 12 h and the lack of need for
      radiolabelled probes also increase the convenience of this protocol.

PMID- 9279968
TI  - Effects of dietary fluoride and magnesium supplements on cyclic adenosine
      monophosphate (cAMP), calcium and magnesium levels in aorta of genetically
      hypercholesterolaemic RICO rats.
AB  - Previous observations have suggested that low intakes of fluoride prevent
      pathological calcifications of internal organs, including the aortic wall, in
      experimental animals, fed a basically low magnesium diet. Our group found
      recently that fluoride has some potentially preventive effect against
      atherosclerotic serum lipid profiles in genetically hypercholesterolaemic rats.
      To study whether the apparently positive potential of fluoride against
      atherosclerosis is also reflected in aortic tissue, through its well known
      activation of adenylate cyclase, the aortic cAMP content of the rats used in our
      recent study was determined. Out of a total of 56 male RICO rats, mean weight 160
      g, the control group C was fed an adequate diet, with 44% sucrose, a magnesium
      content of 883 p.p.m. and with 0.5% cholesterol. Group D had the same diet as
      group C except that the magnesium content was reduced to 200 p.p.m. Group E had
      the same diet as group D but with the fluoride content elevated from 1.9 to 12
      p.p.m. Group G had the same diet as group E but with the magnesium content
      elevated from 200 to 300 p.p.m. After a feeding period of 6 weeks, the aortas of
      the animals were removed, cleaned and kept at -70 degrees C until analysed. The
      mean cAMP content of the aortas, measured by radioimmunoassay, in groups C, D E
      and G was 439, 546, 681, and 1394 mumol mg-1 protein, respectively. In group G
      only, the cAMP content was significantly higher than that of the other groups (p
      < 0.001). The mean calcium and magnesium contents of the aortas of different
      groups did not significantly differ from each other. Thus in RICO rats, fed a
      high-sugar low-magnesium diet with cholesterol, supplementation of the diet with
      a small amount of fluoride elevates the cAMP content of the aorta, provided that
      the intake of Mg is not very low.

PMID- 9279969
TI  - Lisinopril improves endothelial dysfunction in hypertensive NIDDM subjects with
      diabetic nephropathy.
AB  - Endothelial dysfunction is a prevalent phenomenon in non-insulin dependent
      diabetic (NIDDM) patients with hypertension and albuminuria, and may contribute
      to the development and progression of cardiovascular disease, which is the main
      cause of the high morbidity and mortality observed in these patients. Therefore
      the aim of our study was to evaluate whether inhibition of angiotensin-converting
      enzyme (with lisinopril 10-20 mg day-1) could ameliorate endothelial dysfunction
      more than reducing blood pressure with conventional antihypertensive treatment
      (atenolol 50-100 mg day-1), usually in combination with a diuretic. We performed
      a 12-month prospective, randomized, double-blind, parallel study in 43
      hypertensive NIDDM patients with diabetic nephropathy (21 treated with lisinopril
      and 22 with atenolol). The following variables were measured: 24-h ambulatory
      blood pressure (ABP); transcapillary escape rate of albumin (TERalb; i.e. initial
      disappearance of intravenously injected 125I-labelled human serum albumin); serum
      concentrations of von Willebrand factor (vWF), using ELISA, and urinary albumin
      excretion rate (UAE). Data are presented for 32 patients (16 lisinopril and 16
      atenolol; age 60 years, SD 8; 25 males) out of 35 who completed the study and had
      valid measurements of TERalb. At baseline the two groups were comparable; TERalb
      (8.5 (SEM 0.6) vs. 7.2 (0.4)%); vWF (2.09 (range 0.82-4.34) vs. 1.97 (0.95-3.86)
      IU ml-1; UAE 916 (x/divided by antilog SEM 1.3) vs. 1444 (1.2), and mean ABP 110
      (SEM 3) vs. 113 (2) mmHg, in the lisinopril and atenolol group, respectively.
      During follow up, the mean ABP was equally reduced in the lisinopril and atenolol
      group, by 12 (SEM 2) vs. 10 (2) mmHg, respectively, TERalb decreased in the
      lisinopril group by 0.6 (SEM 0.7)%, whereas it increased in the atenolol group
      1.5 (0.5)%; the mean difference was 2.2% (95% CI, 0.5 to 3.9; p = 0.015). UAE was
      reduced by 45% (95% CI, 25 to 60) in the lisinopril group vs. 10% (-15 to 30) in
      the atenolol group (p = 0.014). Serum vWF was not changed during follow up in
      either group. Our study suggests that lisinopril has both reno- and
      vasculoprotective properties in hypertensive NIDDM patients with diabetic
      nephropathy.

PMID- 9279970
TI  - Macrolipasaemia in a patient with pancreas divisum and acute abdominal pain: a
      case report.
AB  - This study describes a rapid increase of serum lipase activity during an episode
      of severe abdominal pain in a female patient with macrolipasaemia and pancreas
      divisum. Serum lipase activity was persistently elevated in the patient with
      simultaneously low levels of amylase activity which only increased in association
      with endoscopic retrograde cholangiopancreatography. Polyethylene glycol
      precipitation experiments, as well as the results of exclusion chromatography,
      demonstrated that the high lipase activity was due to a macromolecule of
      approximately 200000 Da. Affinity chromatography and immunological investigations
      further indicated that the atypical time-course of lipase activity was not due to
      alterations of the patient's lipase, but due to lipase-binding autoantibodies
      resulting in the formation of immune complexes between lipase and immunoglobulin
      G lambda. Our results show that macrolipasaemia must be considered as a possible
      cause in patients with unexplained raised serum lipase activity.

PMID- 9279971
TI  - Measurement of fibrinolytic components in human tissue.
AB  - The fibrinolytic system is involved in the resolution of thrombi and in tissue
      repair. Quantitation of the activators and inhibitors of this system at tissue
      level is crucial to further characterise these processes. Hitherto, there have
      been difficulties in measuring the individual components of the plasmin system in
      human vascular and peritoneal tissue. The aim of this study was to develop a
      protocol allowing quantitation of activators and inhibitors of plasmin generation
      at the tissue level. Following a strict protocol in the processing of tissue, the
      efficiency of extraction in tissue homogenisates was compared using buffers
      containing acetic acid, 1% Triton X-100 and thiocyanate. The influence of
      different modalities of normalisation was investigated by normalising to wet
      weight, total protein content, protein content in supernatant or DNA. Using the
      protocol, all buffers extracted components of the plasmin system sufficiently for
      detection. The acetic acid buffer yielded the greatest amount of protein, and in
      extracting plasminogen activators was comparable to the thiocyanate buffer and
      significantly more efficient than the Triton buffer (p < 0.05). The relationship
      between the individual components was unaltered by different means of
      normalisation. The protocol described, using an acetic acid buffer and
      normalising to wet weight, seems to be a simple and efficient technique for
      measuring components of the fibrinolytic system, at least in the tissues
      investigated.

PMID- 9279972
TI  - Plasminogen activator inhibitor-1 (PAI-1) content in platelets from healthy
      individuals genotyped for the 4G/5G polymorphism in the PAI-1 gene.
AB  - We have studied PAI-1 activity and antigen content in platelets and in plasma
      from 37 healthy individuals who were also genotyped for the 4G/5G polymorphism in
      the PAI-1 promoter region. The PAI-1 data obtained were compared with the
      vitronectin and the beta-thromboglobulin contents in platelets from the same
      individuals. A highly significant correlation between PAI-1 activity and PAI
      antigen was obtained, both in the plasma samples (p < 0.0001) and in the platelet
      lysates (p < 0.001). The specific activity of PAI-1 was higher in plasma than in
      the platelet lysates, but interindividual variation was more pronounced among
      platelet lysates (range 159,000-1,190,000 U/mg). The calculated specific activity
      of PAI-1 in platelets seems to be higher than what could be expected from
      theoretical considerations regarding half-life of platelets in the circulation
      and conversion of functional PAI-1 to latent PAI-1. On analysis of the influence
      of the 4G/5G polymorphism, individuals who were homozygous for the 4G allele
      seemed to have higher levels of PAI-1 activity and antigen in the platelet
      lysates, when compared to the other genotypes. In platelet lysates, but not in
      plasma, a strong correlation was observed between the concentrations of PAI-1 and
      beta-thromboglobulin (r2 = 0.70, p < 0.001). Vitronectin could be detected in the
      platelet lysates in low concentrations (497 +/- 334 micrograms/l). However, using
      a newly developed ELISA method for PAI-1-vitronectin complex we failed to
      demonstrate such a complex in the platelet lysates. Therefore, the mechanism
      involved in stabilization of PAI-1 activity in the platelets is at present not
      understood.

PMID- 9279973
TI  - Clear cell tumors of unknown nature and origin: a systematic approach to
      diagnosis.
AB  - Not infrequently, surgical pathologists encounter malignant neoplasms composed of
      clear cells, the sources and natures of which are indeterminate on the basis of
      conventional morphological study. In this context, it is frustrating that tumors
      of completely dissimilar lineage can show strikingly similar microscopic
      appearances; moreover, anatomic location provides few if any definitive clues to
      the likely final diagnosis in many cases of clear cell neoplasia. Because of
      these factors, it is necessary to systematically pursue the same approach to the
      pathological assessment of clear cell tumors, routinely considering not only
      clinical and radiologic details but also the possible application of
      immunohistology, electron microscopy, and cytogenetics. This review provides
      algorithmic schemes by which such techniques can be applied, as well as their
      potential drawbacks and limitations.

PMID- 9279974
TI  - Clear cell tumors of the breast.
AB  - Clear cells are common in both healthy and pathological breast tissue and are
      dependent on processing of the specimen in question. Clear cell mammary tumors
      represent patterns rather than entities because their cytoplasmic lucency is most
      often caused by artifactual extraction of substances stored in the cytoplasm.
      Loss of mucosubstances, glycogen, or lipid in processing will produce clear cell
      alteration. Therefore, this feature may be observed in apocrine, endocrine,
      myoepithelial, and adenomyoepithelial lesions as well as in ordinary types of
      breast carcinoma. The use of immunocytochemistry and electron microscopy allows
      for detailed characterization of cytoplasmic contents and delineation of the
      reasons for optical transparency. Clear cell tumors do not appear to have a
      significantly different biological behavior when matched with their nosological
      nonclear cell counterparts in regard to stage and grade.

PMID- 9279975
TI  - Clear cell neoplasms of the endocrine system and thymus.
AB  - Clear cell tumors of the endocrine system and thymus are rare lesions with which
      surgical pathologists have only infrequent contact. As a result, these neoplasms
      may be misinterpreted and incorrectly classified. This review considers the
      histological, immunohistochemical, and ultrastructural features of clear cell
      pituitary adenomas, parathyroid tumors, pancreatic endocrine neoplasms,
      adrenocortical proliferations, and thymic malignancies. Emphasis is placed
      throughout on differential diagnosis with microscopically-similar lesions. Clear
      cell endocrine tumors and thymic lesions manifest a variety of potential
      lineages, including examples with epithelial, neural, germ cell, and lymphoid
      differentiation. Because of the wide differences in behavior and recommended
      treatment in this group, accuracy in diagnosis is essential.

PMID- 9279976
TI  - Clear cell tumors of the salivary glands, jaws, and oral mucosa.
AB  - Clear cell tumors of the oral mucosa, jaws, and salivary glands constitute a
      heterogeneous group of lesions which may be either odontogenic, salivary gland,
      or metastatic in origin. Clear cells in these proliferations most frequently
      result from fixation artifact but may also be the result of cytoplasmic
      accumulation of water, glycogen, intermediate filaments, or immature zymogen
      granules, or a paucity of cellular organelles. Odontogenic neoplasms that may be
      characterized by a predominantly clear cell component include odontogenic
      carcinoma, ameloblastoma, and calcifying epithelial odontogenic (Pindborg) tumor.
      Clear cell tumors of salivary gland origin are almost invariably malignant in
      nature but they do include two benign lesions; namely, oncocytoma and
      myoepithelioma. Clear cells in acinic cell carcinoma seldom comprise a
      significant portion of the tumor whereas clear cell mucoepidermoid carcinomas can
      readily be identified by an admixture of clear-squamoid, mucous and intermediate
      cells. Lesions previously reported as "clear cell adenoma" "clear cell carcinoma,
      or glycogen-rich carcinoma" can be divided into the distinctive biphasic
      epithelial-myoepithelial carcinoma and monophasic lesions which have been shown
      to be either myoepithelial or ductal in origin. The latter are primarily
      represented by the recently described "hyalinizing clear cell carcinoma." The
      most common metastatic clear cell tumor in the oral mucosa and the jaws is the
      renal cell carcinoma. However, metastases of melanoma and malignant clear cell
      tumors of the prostate, bowel, thyroid, and liver must also be considered.

PMID- 9279978
TI  - HIV and AIDS: can we develop a common framework for analysis and action?

PMID- 9279977
TI  - Clear cell tumors of the alimentary tract and abdominal cavity.
AB  - Clear cell neoplasms of the abdominal organs are represented by a variety of
      epithelial and mesenchymal neoplasms, of varying malignant potential. Several
      varieties of clear cell carcinomas, including those with tubulopapillary,
      hepatoid, colloid, or neuroendocrine features, have been described, as well as
      several benign epithelial neoplasms. These epithelial tumors have been reported
      in the gastrointestinal hollow viscera, as well as the liver, pancreas, and
      biliary tract. A second major consideration is the mesenchymal-derived
      gastrointestinal stromal tumors, which also may feature clear cells, and comprise
      a spectrum of biological behavior. Miscellaneous lesions include clear cell
      variants of melanoma and mesothelioma. This review includes histological details
      of the various entities, as well as important histochemical, immunohistological,
      and ultrastructural features. Pertinent differential diagnostic points are
      stressed, including distinction of the primary clear lesions from relevant
      metastatic neoplasms.

PMID- 9279979
TI  - Assessing the economic impact of a rapid on-site malaria diagnostic test.
AB  - A set of three models has been developed for assessing the economic impact of
      existing and new malaria diagnostic technology, specifically microscopy of blood
      slides and rapid on-site diagnostic tests (RDT). The models allow for phased
      introduction of the new technology in targeted areas. The derived computer
      software program facilitates evaluation of costs to the supplier, to the consumer
      and aggregate costs, with comparison among the three models to give relative
      costs of progressive transition from blood slides to RDT technology. The models
      and the related software program can assist planners in the health sector in
      determining costs of current programs and assessing the potential economic impact
      of introducing rapid on-site diagnosis. Details of the models and the operational
      software program are available on request.

PMID- 9279980
TI  - Pharmacokinetics of proguanil in malaria patients treated with proguanil plus
      atovaquone.
AB  - Clinical studies have shown atovaquone (ATQ), a new blood schizontocidal drug, in
      combination with proguanil (PROG) to be very effective in the treatment of acute
      multidrug-resistant falciparum malaria. The multiple dose pharmacokinetics of
      PROG were determined in Thai patients with acute falciparum malaria given PROG
      alone (200 mg PROG twice a day for 3 days, n = 4) and concurrently PROG and ATQ
      (200 mg PROG and 500 mg ATQ twice a day for 3 days, n = 12). There were no
      statistical differences (p > 0.05) in the area under the plasma drug
      concentration-time curve (AUC), apparent oral clearance (CL/F) and elimination
      half-life (t1/2) of PROG between patients given PROG alone and PROG/ ATQ. The
      median (range) kinetic values of PROG in patients given PROG alone and PROG/ATQ
      were respectively: CL/F = 1.25 l/h/kg (0.99-1.45) and 0.95 (0.73-1.32) l/h/kg,
      and t1/2 = 14.2 hours (9.3-16.8) and 13.6 hours (9.1-17.6). The CL/F and t1/2 of
      PROG in the Thai patients treated with the 2 treatment regimens were also
      comparable to values reported in healthy Thai volunteers given a standard
      prophylactic dose (200 mg PROG). The results of this preliminary study suggest
      that ATQ is unlikely to affect the pharmacokinetics of PROG to a clinically
      important extent at an ATQ dosage of 500 mg twice a day for 3 days in malaria
      infected patients.

PMID- 9279981
TI  - Primary sequence of the envelope glycoprotein of a dengue type 2 virus isolated
      from patient with dengue hemorrhagic fever and encephalopathy.
AB  - Dengue viruses exist in nature as a collection of highly similar but not
      identical members (quasispecies). In order to correlate the presence of viral
      quasispecies with rare occurrence of unusual clinical manifestations in dengue
      infected individuals, a dengue type 2 virus was isolated from the peripheral
      blood of a 12-year-old boy who presented with fever, headache, drowsiness and
      tonic seizure of the left arm, and subsequently manifested symptoms and signs of
      dengue hemorrhagic fever. Analysis of the envelope glycoprotein sequence of the
      encephalopathy-associated virus and two other dengue type 2 viruses from the same
      epidemic season in Chiang Mai, Thailand revealed that all three viruses belonged
      to the subtype IIIa of the five-subtype phylogenetic nomenclature system for
      dengue type 2 virus. The encephalopathy-associated dengue virus was more
      divergent from the others and was characterized by an Ala-->Val substitution at
      the position 173 of the envelope glycoprotein. This substitution mapped to the
      central domain 1 which was not known to be involved directly in envelope-receptor
      interaction.

PMID- 9279982
TI  - Rapid detection and identification of dengue viruses by polymerase chain reaction
      (PCR).
AB  - A polymerase chain reaction (PCR) method using sets of newly designed primers for
      rapid detection and simultaneous identification of dengue virus serotypes was
      developed and tested. The test is based on two sets of primers specific within
      the envelope (E) and non-structural (NS1) regions of the dengue-virus genome. Two
      sets of universal primers that bind to two target sequences which are shared by
      all the four serotypes of the virus within the E and NS1 regions are used. The
      resulting products are further amplified by another pair of inner or nested
      universal primers, which also bind to another set of shared sequences within the
      E and NS1 regions, respectively. The nested PCR of both the E and NS1 regions can
      detect dengue virus of all the four serotypes at a sensitivity of 1 plaque
      forming unit (pfu) or less. For the identification of serotypes, a mixture of
      four pairs of serotype-specific primers, specific to the E region, was used. The
      primers have been designed to bind to serotype specific sequences within the
      regions flanked by the outer universal primers, and giving the amplified products
      of different sizes, each corresponds to one particular serotype (405 bp for Den1,
      346 bp for Den2, 196 bp for Den3, and 143 bp for Den4). A protocol has been
      developed and successfully applied to detect dengue virus in cell-culture
      supernatants and patients sera. The technique is simple and rapid, capable of not
      only detecting the dengue virus but also identifying the serotypes of the virus
      in clinical specimens.

PMID- 9279983
TI  - Improved amplification system for detection of hepatitis C virus genome that
      simultaneously differentiates viral genotypes.
AB  - An improved system for amplification of hepatitis C virus genome (HCV) was
      developed based on a multiplex nested polymerase chain reaction format. Two sets
      of oligonucleotide primers were used simultaneously. One was derived from the
      conserved sequences in the 5' non-coding region of the viral genome which can
      bind to the viral genome of all genotypes. The other set of primers was designed
      from a sequence in the nonstructural-5 region of HCV. HCV genotypes 1 and 3 can
      be differentiated by the banding patterns of amplified DNA products. All of 39
      samples containing the HCV genotype 1 could be amplified with primers in the 5'
      non-coding region only, whereas 92% of those with genotype 3 could be amplified
      by both primer sets. In addition, HCV RNA can be detected in 81% of 84 anti-HCV
      positive blood donors and in 0% of 34 anti-HCV-negative cases. Of the HCV RNA
      positive specimens, 69% showed genotype 1-like patterns while 31% showed genotype
      3-like patterns. The detection rate of HCV RNA in this study was much higher than
      that in our previous report due to the improvement of new primers which can
      detect all genotypes of the virus. In conclusion, this improved amplification
      system is a sensitive method for rapid identification of HCV RNA in clinical
      specimens that can simultaneously differentiate the two most common genotypes of
      HCV found in Thailand.

PMID- 9279984
TI  - Acute hemorrhagic conjunctivitis outbreak in Thailand, 1992.
AB  - The 260 cases of acute hemorrhagic conjunctivitis seen at Siriraj Hospital during
      October to December, 1992 were studied. Evidence of coxsackie virus A24 variant
      (CA24v) infections was demonstrated in 76.8% of 95 cases. The isolation rates
      from conjunctival swabs and throat swabs were 68.2% and 32.8%, respectively. A
      four-fold rising titer of neutralizing antibody was shown in 59.5% of 42 cases.
      The disease was characterized by a short incubation period, sudden onset, a mild
      and self-limited course within 5 days without ocular sequelae. Lacrimation,
      swelling lida, itching, foreign body sensation and periorbital pain were common
      features with bilateral involvement in the majority of cases. Approximately 48%
      of eyes had a mucopurulent discharge. Preauricular lymphadenopathy, keratitis and
      subconjunctival hemorrhage were observed in 16.2%, 12.6%, and 10.1% of affected
      eyes, respectively. Respiratory disturbances accompanied the eye signs in some
      cases. Only one case developed neurological complications: facial palsy was
      observed for three months without recovery.

PMID- 9279985
TI  - Evaluation of a canine rabies vaccination campaign and characterization of owned
      dog populations in the Philippines.
AB  - A mass canine rabies vaccination campaign in Sorsogon Province, the Republic of
      the Philippines, was conducted in April and May 1993. From 1 to 14 days following
      visits by vaccination teams to 30 selected villages (barangays), survey teams
      revisited the barangays to assess vaccine coverage. Modified cluster survey
      methods were used to gather information about vaccine coverage in the owned-dog
      population (210 households) and about characteristics of owned-dogs and factors
      influencing owner willingness to participate in the campaign. Vaccinated dogs
      were identified by asking owners about receipt of certificates given by the
      vaccinating teams and examining each animal for a special collar or paint mark
      placed on the animal at the time of vaccination. Survey results indicated that
      73% (178/243) of eligible dogs were vaccinated and 82% of vaccinated dogs were
      marked with a collar or paint. Dogs were owned by 69% of households and ranged in
      age from 3 days to 13 years (median = 1 year), and the ratio of male to females
      dogs was 1:1. The dog-to-human ratio was 1:3.8, with an average of 1.4 dogs per
      household or 2.1 dogs per dog-owning household. Most dogs were kept as guards
      (83%) and most were free-ranging (85%). The most common reasons dogs were not
      vaccinated included they could not be restrained (11/64), the owner was not home
      (10/64), and fear of injury resulting from vaccination (10/64). The owners of 20%
      of vaccinated dogs reported some adverse reaction in their pet. Improved vaccine
      coverage was significantly associated with restrained dogs kept primarily for
      guard functions by owners who received information about the vaccination campaign
      from multiple sources. Vaccine coverage was sufficiently high to potentially
      control rabies transmission among dogs through herd immunity and indicated a
      successful vaccine campaign.

PMID- 9279986
TI  - Pulmonary tuberculosis in a BCG vaccinated area: relationship of disease severity
      with immunological and hematological parameters and drug resistance patterns.
AB  - Clinical hematological and immunological parameters were studied in a group of
      145 pulmonary patients with active tuberculosis, from a defined area of Karachi
      (Kharadar) belonging to the lower socioeconomic strata. Although clinical
      symptomatology could not differentiate the extent of lung involvement, a majority
      (69.6%) of the patients were diagnosed radiologically as having moderately
      advanced pulmonary disease. The peak number of patients were in their second
      decade of life. No differences were observed in the extent of disease based on
      age or gender. All hematological parameters for the group were in the normal
      ranges except for low levels of hemoglobin (9.58 +/- 1.55 SD; normal range 12-14
      mg/dl) and a high ESR (90 +/- 31 SD; normal range 0-13 mm/hour). A negative
      correlation of PPD skin test induration (r = 0.21, p = 0.02), and a positive
      correlation of total white blood cell (r = 0.20; p = 0.015) was observed with the
      amount of lung tissue involved. The resistance amongst the strains for the four
      first line anti-tuberculosis agents was found to be: isoniazid = 27.4%;
      ethambutol = 14.5%; rifampicin = 11.29% and streptomycin = 12.9%. Multi-drug
      resistance to the most commonly prescribed combination (rifampicin and
      ethambutol) was 8.06%. Drug resistance patterns to individual drugs were
      comparable with resistance patterns observed in strains from greater Karachi at
      The Aga Khan Hospital during the same period. Such studies should provide
      improved rationale for patients diagnosis and treatment.

PMID- 9279987
TI  - Indirect hemagglutination antibodies against Burkholderia pseudomallei in normal
      blood donors and suspected cases of melioidosis in Malaysia.
AB  - Interpretation of the indirect hemagglutination test (IHA) for melioidosis in
      endemic areas is difficult because of the presence of antibodies in apparently
      healthy individuals. Fifty-three out of 200 healthy blood donors in Malaysia
      showed positive antibody titers (> or = 1 : 40) against Burkholderia
      pseudomallei. Seven percent had an IHA titer of 1 : 40, 11% had an IHA titer of 1
      : 80 while 8.5% had a titer > or = 1 : 160. Out of 258 sera sent for melioidosis
      serology, 7% of the patients had an IHA titer of 1 : 40, 9% had an IHA titer of 1
      : 80 while 20% had an IHA titer of > or = 1 : 160. If a titer of > or = 1 : 80 is
      taken as cut off point for positivity, 29% of the patients had positive
      melioidosis serology. Increasing the positivity threshold may jeopardize the
      sensitivity of the test. A more specific and sensitive test is needed.

PMID- 9279988
TI  - Further observations on comparison of immunization coverage by lot quality
      assurance sampling and 30 cluster sampling.
AB  - Lot Quality Assurance Sampling (LQAS) and standard EPI methodology (30 cluster
      sampling) were used to evaluate immunization coverage in a Primary Health Center
      (PHC) where coverage levels were reported to be more than 85%. Of 27 sub-centers
      (lots) evaluated by LQAS, only 2 were accepted for child coverage, whereas none
      was accepted for tetanus toxoid (TT) coverage in mothers. LQAS data were combined
      to obtain an estimate of coverage in the entire population; 41% (95% CI 36-46)
      infants were immunized appropriately for their ages, while 42% (95% CI 37-47) of
      their mothers had received a second/ booster dose of TT. TT coverage in 149
      contemporary mothers sampled in EPI survey was also 42% (95% CI 31-52). Although
      results by the two sampling methods were consistent with each other, a big gap
      was evident between reported coverage (in children as well as mothers) and survey
      results. LQAS was found to be operationally feasible, but it cost 40% more and
      required 2.5 times more time than the EPI survey. LQAS therefore, is not a good
      substitute for current EPI methodology to evaluate immunization coverage in a
      large administrative area. However, LQAS has potential as method to monitor
      health programs on a routine basis in small population sub-units, especially in
      areas with high and heterogeneously distributed immunization coverage.

PMID- 9279989
TI  - Immunity to diphtheria in women of childbearing age in Delhi in 1994: evidence of
      continued Corynebacterium diphtheriae circulation.
AB  - Blood samples from 171 full-term pregnant women (aged 18-38 years) of middle
      socioeconomic status from Delhi were tested for diphtheria antitoxins by indirect
      hemagglutination (IHA) test. History of primary immunization/clinical diphtheria
      during childhood was not ascertainable, but none had been revaccinated against
      diphtheria at any time. About 94% women had very high antitoxin titers (> or =
      0.125 IU/ ml); none had antitoxin titer less than 0.015 IU/ml, the minimum
      protective level. The titers were uniformly high in all age groups. However,
      women having 2 or more children had significantly higher antitoxin titers than
      those having no or one child (p < 0.01). The results from this study and
      historical data on diphtheria in Delhi are compatible with continued transmission
      of C. diphtheriae in recent times in Delhi which is of sufficient magnitude to
      boost the antitoxin levels in adults, especially mothers having two or more
      children. The study highlights the need of increasing the immunization coverage
      with DPT among children to reduce the transmission of Corynebacterium
      diphtheriae.

PMID- 9279990
TI  - Seroprevalence and risk factors of human cysticercosis in a community of
      Shandong, China.
AB  - A community-based seroepidemiologic survey on Taenia solium cysticercosis in
      humans was carried out in Shandong Province, China. Blood specimens from 2,898
      residents were collected and examined for anti-cysticercus antibody. Information
      on demographic and potential risk factors was obtained using a standardized
      questionnaire. The overall seroprevalence of cysticercosis was 3.2%.
      Seropositivity tended to increase with age ranging from 1.8% in children under 6
      years of age to 5.7% in those over 60 years old. Distance between village
      residence and the town of the community was negatively associated with
      seropositivity (Chi-square for trend test p = 0.02). Multivariate logistic
      regression analysis identified four risk factors for cysticercosis infection in
      the community: defecating indiscriminately (OR = 1.35, 95% CI 1.01-1.81), being
      unable to identify diseased pork (OR = 4.09, 95% CI 1.53-10.97), raising pigs (OR
      = 1.36, 95% CI 1.09-1.69), and more than 60 years old (OR = 1.49, 95% CI 1.10
      2.02. These findings have implications for developing appropriate strategies for
      the control of Taenia solium cysticercosis in the community.

PMID- 9279991
TI  - Seroepidemiological study of Toxocara infection in Nepal.
AB  - Seroepidemiological study of Toxocara infection in Nepalese people aged more than
      fourteen years was carried out by enzyme linked immunosorbent assay (ELISA) using
      T. canis soluble embryonated egg antigen. Of the total 200 subjects included in
      this study, 162 (81%) were found to possess antibodies to Toxocara spp. Males
      showed higher (85%) antibody positive rates than females (77%). Inhabitants of
      Kathmandu valley showed higher antibody positive rates (84%) compared with those
      living outside of the valley (78%). These differences, however, were not
      significant statistically (p > 0.05). Ethnically, Newar, Rai/Limbu,
      Tamang/Sherpa, Brahmin/Chhetri, Jha/Yadavs, and others (Kami, Damai) showed
      Toxocara antibody positive rates of 85, 85, 83, 70, 77 and 100%, respectively.
      Half of the Toxocara antibody positive subjects (49%) showed an elevated level
      (two plus) of antibody.

PMID- 9279992
TI  - The evaluation of the 29 and 31 kDa antigens in female Angiostrongylus
      cantonensis for serodiagnosis of human angiostrongyliasis.
AB  - The objective of this study was to evaluate the crude somatic extract of female
      Angiostrongylus cantonensis by ELISA and to evaluate the 29 kDa and the 31 kDa
      components of female worm by EITB for serodiagnosis of human angiostrongyliasis.
      Using ELISA, cross reaction occurred among all sera tested except capillariasis.
      The sensitivity, specificity, positive and negative predictive values of ELISA
      were found to be 100%, 66.8%, 27.1% and 100% respectively. Using EITB, The 29 kDa
      component cross-reacted with most of the heterologous sera while the 31 kDa
      component was recognized by 69.2% (18/26) sera from angiostrongyliasis patients,
      cross-reacted only with trichinellosis, trichuriasis and opisthorchiasis sera.
      This component may possibly used as reliable agents for angiostrongyliasis out of
      other tissue infected helminthiasis. The sensitivity, specificity, positive and
      negative predictive values of EITB for the 31.0 kDa component were 69.2%, 82.4%,
      46.2% and 92.5% respectively.

PMID- 9279993
TI  - Application of local products R-phycoerythrin and monoclonal antibody as a
      fluorescent antibody probe to detect Entamoeba histolytica trophozoites.
AB  - R-phycoerythrin (R-PE) was extracted from red algae, Gracilaria fisheri from
      Pattani Province, Thailand, with 50 mM sodium phosphate buffer, pH 7.0, followed
      by precipitation with 30-50% final concentration of saturated ammonium sulphate
      solution at 0 degree C. The precipitate was further purified by DEAE-cellulose
      (DE-52) column chromatography. The purified R-PE showed a single band of Mr 240
      kDa by polyacrylamide gel electrophoresis with the maximum absorption and maximum
      fluorescence emission at 565 nm and at 573 nm respectively, and the OD ratio of
      565 to 280 nm was 6.7. The IgG fraction of a murine monoclonal antibody (Eh208C2
      2 MIgG) raised against trophozoites of HM-1: IMSS strain of pathogenic E.
      histolytica was conjugated with purified R-PE by using the heterobifunctional
      compound N-succinimidyl3-(2-pyridyldithio)propionate (SPDP). The conjugate was
      shown by direct immunofluorescent antibody (DIFA) assay to stain specifically
      both the culture-derived and stool-derived E. histolytica trophozoites.

PMID- 9279994
TI  - Opisthorchis viverrini: effect of praziquantel on the adult tegument.
AB  - Ultrastructural changes of the tegument of adult liver flukes, Opisthorchis
      viverrini, after in vitro incubation in Minimal Essential Medium containing 0,
      0.1, 1.0 and 10.0 micrograms/ml of anthelminthic praziquantel for 5, 15, 30, 45
      and 60 minutes were investigated by scanning (SEM) and transmission (TEM)
      electron microscopy. SEM observations showed that the surface damage was composed
      of blebbing due to the swelling of microvilli, followed later by the disruption
      of these structures to form lesions that caused the erosion and desquamation of
      the surface. Sensory papillae, by contrast, appeared relatively unaffected. The
      surface changes could be observed at all doses but the extent of damage increased
      with increasing duration of incubation and concentration of the drug. The ventral
      as well as the dorsal surfaces exhibited similar change, whereas the anterior
      part tended to be damaged less than the posterior part. Under TEM observations,
      the earliest sign of changes was the depolymerization of the microtrabecular
      network in scattered foci, which resulted in the formation of non-membrane-bound
      vacuoles under microvilli. The basal infoldings also became dilated, and some
      turned into membrane-bound vacuoles in the basal zone. Subsequently, microvilli
      became enlarged, and eventually formed blebs that later rupture to form lesion
      spots as observed in the SEM. Finally, the microtrabecular network in all regions
      broke down, creating vacuoles of various sizes throughout the tegument, leading
      to its total disintegration and detachment. The sequence of morphological changes
      was generally similar at all doses; however, the changes occurred faster at the
      higher doses and the longer incubation times. In addition, at the longer
      durations myofilaments in most muscle cells also became depolymerized, while
      microtubules were unchanged by the drug. Therefore, it is possible that
      praziquantel, through its induction of Ca2+ influx, causes depolymerization of
      the microtrabecular network that leads to the vacuolization, swelling, blebbing,
      and eventually the disruption and detachment of the tegument, and the breakdown
      of myofilaments in the muscle cells.

PMID- 9279995
TI  - Opisthorchis viverrini: the effects of colchicine and cytochalasin B on the adult
      tegument.
AB  - The roles of the tegumental cytoskeleton were tested by treating adult flukes
      with colchicine and cytochalasin B. Following a short incubation period (10-20
      minutes), colchicine disrupted microtubules in the tegumental cells' processes
      which, in turn, affected the transport of dense granules from the cells' soma to
      the tegument; as a result some of these granules were fused together to form
      membrane-bound vacuoles. In addition, at many spots microtrabeculae were also
      depolymerized, which resulted in the formation of non-membrane-bound vacuoles and
      the distension of microvilli to form blebs, some of which were disrupted. After
      prolonged incubation (120 minutes), general breakdown of the tegumental
      cytoskeleton occurred, and parts of it were sloughed off. In cytochalasin B
      treatment, the responses were similar to those of colchicine but with less
      severity. After a short incubation period (10-20 minutes), the microtrabeculae
      were depolymerized which led to the formation of non-membrane-bound vacuoles in
      the apical and middle zones of the tegument. Later, the tegumental microvilli
      were distended to form blebs but no evidence of tegumental sloughing occurred
      even in prolonged incubation. From these observations, it was concluded that
      microtubules played a role in the translocation of granules from the tegumental
      cells to the tegument which modulated the synthesis of membrane and glycocalyx,
      while microtrabeculae were involved in the maintenance of the structure and
      integrity of the tegument.

PMID- 9279996
TI  - In vitro drug susceptibility of Acanthamoeba castellani to chloroquine,
      ivermectin and fungizon.
AB  - In vitro sensitivity of Acanthamoeba castellani was tested to three drugs:
      Chloroquine, ivermectin and fungizone (amphotericin B). Sensitivity was
      demonstrated to the latter two compounds but not to chloroquine. Thus ivermectin
      and amphotericin B show promise as therapeutic agents against this parasite.

PMID- 9279997
TI  - Utilization of reproductive health services in a mountainous area in Vietnam.
AB  - This study uses data from two surveys performed in 1991 and 1994 in a mountainous
      district of northern Vietnam. The aim was to describe the utilization of family
      planning, antenatal care, delivery and immunization services during a period of
      rapid structural change in the health services in general and implementation of a
      primary health care project in the study area. This project was aimed at
      increasing access to health services and improving the quality of primary health
      care services. Factors influencing the utilization of reproductive health
      services were analyzed. The contraceptive prevalence among women aged 15-49
      increased significantly from 48% in 1991 to 60% in 1994. The most commonly used
      contraceptive method was intra-uterine devices. The BCG coverage among children
      under five years of age increased from 36 to 70%. The proportion of pregnant
      women receiving three antenatal check-ups, as recommended by the health
      authorities was low and increased slightly from 15% in 1991 to 20% in 1994. About
      one third of the pregnant women were delivered in health care institutions during
      this period. The utilization of family planning, antenatal care and delivery
      services varied with ethnicity and was positively related to the mother's
      educational level both in 1991 and 1994. There is a need to strengthen the
      reproductive health services, especially antenatal care and delivery services, in
      terms of improving the quality of care and accessibility to women. Efforts should
      be made to reach women with a low education level as well as those belonging to
      ethnic minorities.

PMID- 9279998
TI  - Impacts of training of village health volunteers in reduction of morbidity from
      acute respiratory infections in childhood in southern Thailand.
AB  - In 1990, the Ministry of Public Health of Thailand started a five-year education
      program on management of cases with acute respiratory infection (ARI). The
      objective of this-study was to test whether such a program could reduce the
      average number of sick days of the target children. 30 villages in the study
      district were randomly allocated into 15 study and 15 control villages. A 2-day
      training workshop for village health volunteers from the study villages was
      conducted. The cohort of children age below 5 years in the two areas were
      followed-up for 19 week in the peak season of the disease. Among the 664 and 649
      target children with 67,083 and 67,984 child-days observed in the study and the
      control villages, 71 and 41 children, respectively, were free from any episode.
      The preventive odds ratio of treatment adjusted for age and village effects =
      0.88, 95% (CI 0.4-1.95). The median of the average sick periods in the
      individuals were 27 and 34 days, respectively. After adjusting for age,
      episodes/month and locality, the ratio of average sick days between children in
      the study and control villages was 0.89 (95% CI 0.76-1.05) or 11% shorter
      duration without statistical significance. The adjusted odds ratios of visiting
      the health center, private clinics, the community hospital and provincial
      hospital were 0.95 (95% CI 0.69-1.25), 1.43 (95% CI 0.98-2.11), 2.01 (95% CI 1.06
      3.82) and 4.71 (95% CI 1.50-14.8), respectively. The training program thus had
      rather little impact on morbidity of the disease but tended to promote
      utilization of higher level of health services by the affected children.

PMID- 9279999
TI  - Prevalance of obesity and overweight in northeastern peninsular Malaysia and
      their relationship with cardiovascular risk factors.
AB  - Height and body weight were measured in 2,284 subjects over 20 years old. The
      subjects were chosen by cluster sampling in 9 districts of Kelantan. Blood was
      drawn after an overnight fast for measurement of cholesterol (chol), triglyceride
      (TG), VLDL and HDL-Chol. Oral glucose tolerance test was performed with 75 g
      glucose. The overall prevalence of overweight [BMI (kg/m2) > or = 25-< or = 30]
      and obesity (BMI > 30) was 21.3% and 4.5% respectively. The overweight and obese
      were significantly younger than the lean subjects. The prevalence of
      hypercholesterolemia (chol > 5.2 mmol/l) in lean, overweight and obese subjects
      was 65.3%, 70.2% and 74.7%, respectively. Impaired glucose tolerance was found in
      16.6% of the lean, 21.6% of the overweight and 32.0% of the obese subjects.
      Diabetes mellitus was found in 7.9% of the lean, 10.5% of the overweight and 6.7
      of the obese subjects. 10.1% of lean, 13.2% of overweight and 23.3% of obese
      individuals were hypertensive. In conclusion, the high prevalence of overweight
      and obesity in Malaysia was associated with adverse lipid and glucose metabolism
      as well as poor blood pressure control.

PMID- 9280000
TI  - Iron status of Filipino infants and preschoolers using plasma ferritin and
      transferrin receptor levels.
AB  - Iron status of 1,861 Filipino infants and preschoolers was evaluated by
      measurements of plasma ferritin (PF), transferrin receptor (TR) and hemoglobin
      (Hb). One group of subjects (Group I) consisted of all anemic subjects together
      with a systematic subsample from the Fourth National Nutrition Survey-Biochemical
      Phase. Results showed that depleted iron stores based on PF (< 12.0 ng/ml) was
      present in 70.0% of infants and 60.5% of preschoolers. Tissue iron deficiency
      based on TR (> 8.5 mg/l) was present in higher proportion (80.0% and 73.7% for
      infants and preschoolers) which was comparable to the proportion of anemia
      (80.3%). In a subgroup of subjects from the Country Program for Children IV
      (Group 2) elevated TR was present in 61.4% of infants and 46.5% of preschoolers.
      A lower proportion of depleted iron stores of 22.7% in infants and 15.2% in
      preschoolers was observed. Correlation test showed that there was a closer
      relationship between Hb and TR (r = -0.42) than Hb and PF (r = 0.20) even if PF
      was expected to give a higher proportion of values below normal. The occurrence
      of anemia in the presence of elevated TR without any decrease in PF values
      suggest that the diagnostic ability of PF could be limited in the presence of
      infection. Therefore, future studies should include biochemical tests such as C
      reactive proteins (CRP) to determine the extent of association between anemia and
      infection.

PMID- 9280001
TI  - Risk factors between analgesic use and chronic nephropathy in Thailand.
AB  - Analgesic abuse is common in Thailand. Heavy use of analgesic may also increase
      risk of chronic nephropathy. However, the extent of this risk remains unclear. We
      carried out a case-control study in three referral hospitals. A total of 84
      patients with newly diagnosed of chronic tubulointerstitial nephritis were
      enrolled as cases. Two control groups were randomly selected, 192 from
      hospitalized patients who had no renal disease and serum creatinine below 1.2
      mg/dl and 166 from relatives of friends visiting the hospitals. Both cases and
      controls were interviewed by a standardized pre-coded questionnaire to obtain
      histories of analgesic use before diagnosis of renal disease. On multiple
      logistic regression analysis, patients whose estimated lifetime use of
      acetaminophen of 1,000 g or more had an increased risk of chronic nephropathy
      compared with non-users, the odds ratio (OR) was 5.9 (95% confidence interval
      (CI) 1.3-25.6, hospital controls) and OR = 5.8 (95% CI 1.04-31.9, visitor
      controls). Also, uses of aspirin showed a similar relationship. Patients who used
      aspirin 1,000 g or more per lifetime had higher risk of chronic nephropathy when
      compared to non-users, the odds ratio were 7.1 (95% CI 2.0-25.8, hospital
      controls) and 20.4 (95% CI 2.4-174.2) for visitor controls. These data indicate
      that analgesic abuse increased risk of chronic nephropathy in Thailand.

PMID- 9280002
TI  - Malnutrition and growth abnormalities in children with beta thalassemia major.
AB  - Abnormal linear growth (stunting) is characteristic of children with beta
      thalassemia major and has been variably and inconsistently attributed to multiple
      different mechanisms. Despite the coexistence of beta thalassemia with deficits
      of several micronutrients, global undernutrition as a principle cause of growth
      abnormalities has not been adequately studied. We prospectively studied 115
      nonsplenectomized children (6 months-6 years, 54 males, 61 girls) with beta
      thalassemia major who has not previously received chelation therapy. Most
      children had abnormal weight-for-age (WAZ) and height-for-age (HAZ) Z scores,
      however female children had lower WAZ (p < 0.0001) and HAZ (p < 0.02) compared to
      males. Mild to moderate degrees of acute wasting was also usual, and two males
      and one female had severe wasting. Severe weight deficits were more prevalent in
      the youngest (p < 0.01) and severe stunting in the older (p = 0.01) children.
      Nearly all children were < 50th percentile for both weight-for-age and height-for
      age, and the majority were < 5th percentile. Of note, children were also
      disproportionately distributed below the 50th percentile for weight-for-height.
      Pre-transfusion hemoglobin was variably associated with anthropometric
      measurements. We conclude that not only is linear growth failure pervasive in our
      population with beta thalassemia major, but varying degrees of wasting are also
      typical. Further, weight deficits occur at an early age and appear to precede
      deficits in linear growth. Abnormal growth is not due to chelation therapy and is
      inconsistently associated with the degree of anemia. These patterns of growth
      abnormalities indicate general malnutrition as an important cause of growth
      failure in children with beta thalassemia.

PMID- 9280004
TI  - Amplification of Bcl I region of the factor VIII gene by PCR.
AB  - A study was initiated to amplify by polymerase chain reaction (PCR), a short
      factor VIII gene fragment containing the Bcl I restriction site from hemophilia
      patients using published primer sequences. Preliminary findings indicated that
      the resulting fragment is 142 bp long. This fragment, when digested with Bcl I
      restriction enzyme produced two fragments, 99 bp and 43 bp in length.
      Polymorphism in the Bcl I region can be used to detect carrier state in the
      family members of the hemophiliacs.

PMID- 9280003
TI  - Frequency of alpha-thalassemia-1 of the Southeast Asian-type among pregnant women
      in northern Thailand determined by PCR technique.
AB  - Five hundred pregnant women were analyzed for the presence of alpha-thalassemia-1
      of the Southeast Asian (SEA)-type by polymerase chain reaction (PCR) technique at
      the Maharaj Nakhon Chiang Mai University Hospital in Chiang Mai during the period
      from April to June 1995. Forty-four of them (8.8%) were recognized as carriers,
      corresponding to a frequency of 0.044. Homozygous alpha-thalassemia-1 of the SEA
      type, the fatal condition of hemoglobin Bart's hydrops fetalis, has an expected
      frequency of 0.00194, or about 2 hydrops fetalis cases per 1,000 births in this
      population.

PMID- 9280005
TI  - Application of deltamethrin-impregnated bednets for mosquito and malaria control
      in Yunnan, China.
AB  - The results of research in China in recent years show that: 1) Different
      laboratory sensitivity of adult Anopheles minimus, An. sinensis and Culex pipiens
      quinquefasciatus to deltamethrin exist in Yunnan. Although the range and duration
      for the use of permethrin and deltamethrin was limited, resistance of An.
      minimus, An. sinensis and Cx. pipiens quinquefasciatus to different extent in
      some areas existed. 2) On walls built with cement and covered with a thin layer
      of lime on which deltamethrin at a dosage of 0.025 g/m2 was sprayed, 100% of the
      mosquitos were stricken down within 3 days, 80% at the 15th day, 50% at the 20th
      day. The residual effectiveness on the bamboo and wood walls was good and could
      last for over 40 days, but on the mud walls a mortality of only 40% on the
      spraying day was observed, indicating that deltamethrin was not suitable for this
      purpose. Deltamethrin spraying reduced total caught mosquitos within 30 days, but
      there was no difference between the effects of deltamethrin (0.025 g/m2) and DDT
      (2 g/m2) at the 60th day. Deltamethrin effect on reducing densities of endophilic
      An. vagus, An. culicifacies and exophilic An. philippinensis was better than that
      of DDT (lasting over 60 days), but its effect on semi-endophilic An. sinensis
      lasted only 15 days. Against An. mininus, it showed good effects within 20 days
      but did not last as long as DDT (60 days). Residual deltamethrin and DDT spraying
      could both control malaria vectors, reduce the infection of infants by malaria,
      and reduce malaria parasite carrier rates (within 50 days). 3) Laboratory
      experiments showed that deltamethrin-impregnated bednets at a dosage of 0.015
      g/m2 had a positive effect on An. minimus. The residual effect of unwashed
      deltamethrin-impregnated bednets at a dosage of 0.015 mg/m2 against An. sinensis
      was apparent and could last for 13 months. When an impregnated bednet was washed
      for the first time at the 12th month, its mortality effect on An. sinensis was
      reduced quickly to lower than 50%. The residual effect could last for 2-3 months
      when washed at the 6th month, but was lost when washed for the second time at the
      12th month. 4) The effects of the impregnated-bednets on An. sinensis were
      different, even opposite, between different investigations. However, the treated
      bednets caused the density of An. minimus in houses to fall by 67.94%, and the
      total density in houses and cattle shelters by 67.91%. Moreover, it could shorten
      the life span of An. minimus. It did not work on the outdoor density of An.
      minimus. It is necessary to integrate with other measures, for achieving the
      desired effect.

PMID- 9280006
TI  - Malaria in Honiara, Solomon Islands: vector studies.
AB  - Adult and larval specimens of anopheline mosquitos were collected throughout
      eastern Honiara during a study into risk factors for malaria illness in adults.
      Species identification was by morphology, DNA probes and by PCR. Only Anopheles
      farauti s.s. were identified from part-night landing catches carried out from
      1900 to 2200 hours. Most mosquitos attracted to humans were culicines. The
      majority of anophelines (85%) were captured between 1900 and 2000 hours. An.
      farauti s.s. larvae were most common but one An. farauti No. 7, and ten An.
      punctulatus larvae were also collected.

PMID- 9280007
TI  - Feeding patterns of Anopheles dirus, the major vector of forest malaria in north
      east India.
AB  - The feeding behavior of Anopheles dirus, the forest breeding, major malaria
      vector in northeast India was studied. The analysis of blood meals collected from
      this mosquito revealed that the species was highly anthropophilic in nature, the
      anthropophilic index being 90.5. The results of bait collection on human and
      cattle bait also confirmed its biting preference for human hosts. The species was
      observed to land on human bait throughout the night, showing prominent biting
      time at 20.00-21.00, 23.00-24.00 and 02.00-03.00 hours during the study period.

PMID- 9280008
TI  - Role of some environmental factors in modulating seasonal abundance of potential
      Japanese encephalitis vectors in Assam, India.
AB  - Temporal changes in the abundance of host-seeking, potential Japanese
      encephalitis (JE) vector mosquitos and the role of some ecological factors that
      are modulating the abundance of vector mosquitos were studied. Vector
      surveillance was conducted for one year in 4 JE prone villages of Dibrugarh,
      Assam. Among potential JE vectors, the most abundant mosquito was Culex vishnui
      s.s. comprising about 22.32%. Maximum density of the mosquito was found during
      the month of April and another peak was observed in the month of September. The
      influence of meteorological factors on the abundance of JE vectors was found to
      vary from species to species. The final multiple regression equations (after
      variables were selected using STEPWISE procedure) consisted of a combination of
      linear, quadratic, cubic and interactive ecological variables and accounted for
      25-98% of the variations in the abundance of JE vector mosquitos. Complex
      interactions among environmental factors, such as minimum and maximum
      temperature, rainfall and flood level are involved in modulating the seasonal
      abundance of mosquitos. A time lag is involved before a cause and effect
      relationship is established between environmental parameters (independent
      variables) and entomological variables (dependent variables). Inundation caused
      by flooding is favorable for mansonioid mosquito species whereas it has an
      adverse effect on non-mansonioid mosquito species.

PMID- 9280009
TI  - Life-cycle, longevity and fecundity of Blomia tropicalis (Acari: Glycyphagidae)
      in a tropical laboratory.
AB  - In the present study on the life-cycle of Blomia tropicalis, freshly laid eggs
      were observed until they developed into adults; the development periods between
      stages were recorded. The eggs took an average of 22.9 +/- 6.4 days to develop to
      adults. For longevity experiments, newly emerged adults were kept at 25 degrees C
      and observed until they died. There was no significant difference in longevities
      of the different sexes (p = 0.053). Production of eggs by mated females were
      monitored until egg production stopped and the female died. Mated females and
      males survived an average of 32.2 +/- 15.4 and 30.9 +/- 17.7 days respectively.
      The difference in longevity of the mated females, and males was not significant
      (p = 0.747). Longevity of the mated females was found to be significantly (p <
      0.05) shorter than unmated females.

PMID- 9280010
TI  - Survival of beta and gamma races of Neotricula aperta snail intermediate hosts of
      Schistosoma mekongi in raw waters.
AB  - Beta and gamma races of Neotricula aperta were exposed to naturally raw waters of
      the Sirindhorn reservoir, Mun River and Mekong River in laboratory conditions and
      non supplement on food. Snails of two races could withstand well in variable
      qualities of water within 48 hours. The survival rates of N. aperta in three
      sources of raw water were 100% for the beta race and 97 to 100% for the gamma
      race.

PMID- 9280011
TI  - Allozyme variation among six populations of the freshwater-snail Oncomelania
      hupensis in Zhejiang, China.
AB  - Thirteen enzymes encoded by 16 loci of six population of Oncomelania hupensis in
      Zhejiang, China, were investigated by means of starch gel electrophoresis. Ten
      loci (AO, 6PGD, ME, AKP, OCT-1, HBDH-1, HBDH-2, XDH, MDH and MPI) were
      monomorphic and 6 loci (OCT-2, PGI, AAT, PGM-1, PGM-2 and ACP) were polymorphic.
      Three enzymes (OCT, HBDH and PGM) were encoded by 2 loci. The results indicated
      that there were allozyme variations in two subspecies, O.h. hupensis and O.h.
      fausti in Zhejiang, China. Nei's multilocus genetic distances (D) between
      subspecies ranged from 0.167 to 0.265. Minor genetic distances were detected
      between populations of the same subspecies. The results indicated that the enzyme
      acid phosphatase (ACP) is a possible marker to measure the degree of
      susceptibility of O. hupensis to S. Japonicum.

PMID- 9280012
TI  - Acute viral hepatitis A: a cause of jaundice in typhoid fever.
AB  - A typhoid patient presenting with fever and jaundice is reported. Investigations
      revealed that the patient had both typhoid fever and acute viral hepatitis A.
      Jaundice is a rare clinical presentation in typhoid fever, therefore hepatitis A
      should be considered in typhoid fever and jaundice because both enterically
      transmitted disease may simultaneously occur.

PMID- 9280013
TI  - A severe case of hemorrhagic fever with renal syndrome in Singapore.
AB  - The incidence of human hantavirus infection in Singapore is low. Hitherto, only 2
      cases of hemorrhagic fever with renal syndrome (HFRS) have been reported. A third
      case is reported here of a ragman who had the classical manifestations of HFRS,
      confirmed by serology. In addition, his condition was complicated by liver
      dysfunction and neurological disturbance. After a protracted stay, the patient
      was finally discharged from hospital 5 months after the onset of his severe
      illness.

PMID- 9280014
TI  - Non-0:1 Vibrio cholerae septicemia in thalassemia patients.

PMID- 9280015
TI  - Significant antenatal factors in the development of lumbar spinal stenosis.
AB  - STUDY DESIGN: Adverse factors during pregnancy may permanently stunt the growth
      of the spinal canal. Subsequently, even in an optimal environment the canal
      cannot catch up in growth with the trunk and long bones because of its early
      maturation. The degree of retardation in canal size depends on the severity and
      timing of the adverse effect. The catch-up growth of the long bones mask the
      narrow canal, because the latter does not have growth potential, resulting in an
      adult of sufficient height and good proportions, but with a canal at risk for
      stenosis. OBJECTIVES: To investigate the influence of the antenatal environment
      on the growth of the lumber spinal canal. SUMMARY OF BACKGROUND DATA: To date,
      little is known about the effects of an adverse environment on the growth of the
      spinal canal, and no data have been reported on antenatal influencing factors.
      METHODS: Lumbar magnetic resonance imaging scans from 58 patients were examined.
      Dimensions of the central spinal canals were measured by computerized image
      analysis and compared with the subjects' obstetric data from their mothers'
      pregnancies. RESULTS: The L3 canal was found to be the most sensitive to the
      influence of the examined factors. Gestational age was the most significant
      factor; if short, it resulted in small adult canal. Small placental weight,
      greater maternal age, primiparity, low socioeconomic class, and low birth weight
      were also found to be significant in affecting the growth of the canal.
      CONCLUSIONS: An adverse antenatal environment does have a permanent, retarding
      effect on the growth of the lumbar spinal canal.

PMID- 9280016
TI  - The quantitative anatomy of the thoracic facet and the posterior projection of
      its inferior facet.
AB  - STUDY DESIGN: This study evaluated the dimensions of the thoracic facet from T1
      to T12 and determined the posterior projection of the inferior facet using
      thoracic spine specimens. OBJECTIVES: To evaluate quantitatively the thoracic
      facet and determine the projection of the inferior facet on the posterior aspect
      of the lamina relative to facet hook placement in the thoracic spine. SUMMARY OF
      BACKGROUND DATA: Anatomic evaluation of the thoracic facet has not been
      extensively addressed. No detailed studies of the thoracic facet relative to
      posterior facet hook fixation exist. METHODS: Forty-three thoracic spines from T1
      to T12 were directly evaluated for this study. Anatomic evaluation of the
      thoracic superior and inferior facets included the facet width, height, and
      angulation relative to sagittal plane. The projection of the inferior facet on
      the posterior aspect of the lamina was constructed and measured. RESULTS: In
      general, the male linear and angular parameters were larger than the female ones.
      The average transverse angle of the facets at T1-T12 for both men and women
      ranged approximately from 74 degrees to 88 degrees for the superior facet and 74
      degrees to 108 degrees for the inferior facet. The average inferior thickness
      from T1 to T12 for both sexes ranged from 3 to 5 mm. The posterior projection
      height of the inferior facet was found to be 9 to 12 mm from T1 to T12 for both
      men and women. The distance between the posterior midline and the inferior facet
      projection ranged from 7 to 11 mm at T1-T12 for both sexes. CONCLUSIONS: This
      study may aid in the understanding of the location, angulation, and dimensions of
      the facet and proper placement of hooks into the thoracic facet joint.

PMID- 9280017
TI  - Preliminary design and experimental studies of a novel soft implant for
      correcting sagittal plane instability in the lumbar spine.
AB  - STUDY DESIGN: A novel soft implant design for resisting the instability of the
      lumbar spine in the sagittal plane was mechanically tested. OBJECTIVES: To
      ascertain whether a soft preformed implant made of differing grades of silicone
      would contribute to stabilizing the lumbar spine in the sagittal plane. SUMMARY
      OF BACKGROUND DATA: Methods of stabilizing the lumbar spine in patients who
      present with chronic low back pain have usually concentrated on rigidly fixing
      the associated segment. This has many inherent problems with both the surgical
      methods and the long-term rigidity at and away from the stabilized site. To the
      authors knowledge, no "soft" interspinous spacer that would allow a certain
      amount of flexion but still stabilize the movements associated with instability
      at the level of the lesion has been investigated mechanically as an alternative
      to rigid fixation or prosthetic replacement. METHODS: The apparatus was designed
      to allow a cadaveric lumbar motion segment to be tested in compression at four
      angles of flexion with loads up to 700 N. The intradiscal pressure and sagittal
      plane stiffness were recorded during loading, with and without various sizes of
      the soft silicone implants placed between the spinous processes. RESULTS:
      Insertion of the silicone implants between the spinous processes reduced the
      intradiscal pressure under load at the angles of flexion tested. The size of the
      interspinous space determines the optimal diameter of the implant that afforded
      sagittal stability, the load-bearing contribution of the implant, and the
      prevention of disc space narrowing at the level investigated. CONCLUSIONS: A
      circular silicone spacer placed between the spinous processes appears to
      contribute to the stability of the cadaveric lumbar spine. There are many
      attractions to using a simple, soft implant that can be placed with minimal
      surgery between the spinous processes.

PMID- 9280018
TI  - Effects of chondroitinase ABC and chymopapain on spinal motion segment
      biomechanics. An in vivo biomechanical, radiologic, and histologic canine study.
AB  - STUDY DESIGN: The biomechanical effects of chondroitinase ABC and chymopapain
      related to spinal segmental instability were investigated using a canine model,
      as well by as radiologic and histologic analyses. OBJECTIVES: To evaluate the
      biomechanical, radiologic, and histologic affects on the lumber intervertebral
      disc of chondroitinase ABC compared with chymopapain. SUMMARY OF BACKGROUND DATA:
      No study on the biomechanical effects of chondroitinase ABC has been reported.
      METHODS: Forty-eight lumbar intervertebral discs in eight beagles were randomly
      assigned to three groups and received one of three materials: chondroitinase ABC,
      chymopapain, or buffered saline, using a lateral percutaneous procedure. One week
      after injection, the animals were killed and the lumbar spinal motion segments
      were removed. Spinal segmental instability after chemonucleolysis was evaluated
      in spinal motion segments without posterior elements. Radiologic and histologic
      changes were also investigated. RESULTS: Spinal segmental instability and disc
      space narrowing were more greater in the chymopapain group than in the
      chondroitinase ABC group. Destruction of nucleus and anulus proteoglycans,
      indicated by loss of safranin-O staining, was less intense in chondroitinase ABC
      injected discs. CONCLUSIONS: Chondroitinase ABC results in less spinal segmental
      instability, disc space narrowing, and destruction of proteoglycans in
      intervertebral disc matrix than chymopapain.

PMID- 9280019
TI  - Multidirectional instability of the thoracic spine due to iatrogenic pedicle
      injuries during transpedicular fixation. A biomechanical investigation.
AB  - STUDY DESIGN: Pedicle fracture was simulated in an in vitro model, and its effect
      on multidirectional stability provided by pedicle instrumentation was quantified.
      OBJECTIVES: To quantify the multidirectional flexibility of padicle
      instrumentation due to different iatrogenic pedicle injuries. SUMMARY OF
      BACKGROUND DATA: Misplacement of the screw and iatrogenic pedicle fracture are
      the main complications of pedicle instrumentation. Despite the increasing number
      of clinical studies dealing with this issue, there is little reliable information
      concerning the biomechanical effects of an intraoperative pedicle fracture.
      METHODS: A burst fracture was created in 10 human cadaveric five-vertebrae spine
      specimens, from the middle and lower thoracic spine regions. The fracture was
      stabilized with a semirigid pedicle screw fixation device. To simulate an
      intraoperative pedicle fracture, the pedicles of the instrumented segments were
      resected in four steps. After each pedicle injury, three-dimensional flexibility
      in the form of range of motion and neutral zone of the construct was determined
      and compared with the intact values. RESULTS: Resection of the pedicles had
      little effect on the multidirectional flexion-extension stability provided by the
      instrumentation. There were significant increases of axial rotation in the middle
      thoracic spine when the lateral wall was resected (range of motion, 8.2 degrees
      vs. 3.6 degrees; neutral zone, 4.2 degrees vs. 1.7 degrees), whereas in the lower
      thoracic spine, significant increases occurred only when all the pedicles were
      resected (range of motion, 3.8 degrees vs. 1.4 degrees; neutral zone, 1.1 degrees
      vs. 0.4 degree). Lateral resection of the pedicle resulted in significant
      increases of range of motion and neutral zone for lateral bending in both the
      middle thoracic spine (range of motion, 19.0 degrees vs. 10.0 degrees; neutral
      zone, 2.4 degrees vs. 1.1 degrees) and the lower thoracic spine (range of motion,
      4.3 degrees vs. 2.5 degrees; neutral zone, 0.9 degree vs. 0.3 degree).
      CONCLUSIONS: Resection of the pedicles results in a significant decrease in axial
      rotation and lateral bending stability provided by the instrumentation. This
      effect was higher in the middle than in the lower thoracic spine and may be
      relevant to pedicle fractures produced by pedicle screws used in these regions.

PMID- 9280020
TI  - Acute axis fractures. Analysis of management and outcome in 340 consecutive
      cases.
AB  - STUDY DESIGN: Retrospective review of acute axis fractures treated at a tertiary
      referral center. OBJECTIVE: To determine the optimal treatment of axis fractures
      based on 340 cases from a single institution. SUMMARY OF BACKGROUND DATA: Axis
      fractures account for almost 20% of acute cervical spine fractures. However,
      their management and the clinical criteria predictive of nonoperative failure
      remain unclear. METHODS: Admission imaging studies and clinical variables were
      obtained for 340 consecutive axis fracture patients. Fractures were classified as
      as odontoid Type I, II, or III with dena displacement on admission
      roentgenograms; hangman's fractures of Francis grade and Effendi type; and
      miscellaneous fractures. Treatment methods were documented, and outcomes were
      based on dynamic lateral roentgenograms, clinical examination, or telephone
      interviews at last follow-up. RESULTS: Follow-up data were available in 92% of
      cases. Type II odontoid fractures comprised 35% of all axis fractures, were the
      most difficult to treat, and had the highest nonunion rate (28.4%). Odontoid
      displacement of 6 mm or more was associated with Type II nonunion (chi-square =
      33.74, P < 0.0001). Patients underwent surgical fusion if fracture alignment
      could not be maintained by an external orthosis, or if they had odontoid
      fractures with transverse ligament disruption, Type II odontoid fractures with
      dens displacement of at least 6 mm, or hangman's fractures of severe Francis
      grade or Effendi type. CONCLUSIONS: Type II odontoid fractures have the highest
      nonunion rate and were associated with dens displacement of 6 mm or greater.
      Early surgical fusion is recommended for acute fracture instability despite
      external immobilization, transverse ligament disruption, Type II odontoid
      fractures with dens displacement of at least 6 mm on admission, or severe Francis
      grade or Effendi-type hangman's fractures. Otherwise, nonoperative management is
      sufficient.

PMID- 9280021
TI  - Pedicle screw fixation for nontraumatic lesions of the cervical spine.
AB  - STUDY DESIGN: This retrospective study was conducted to analyze the clinical
      results in 45 patients with nontraumatic lesions of the cervical spine treated by
      pedicle screw fixation. OBJECTIVES: To evaluate the effectiveness of pedicle
      screw fixation in reconstructive surgery for nontraumatic cervical spinal
      disorders. SUMMARY OF BACKGROUND DATA: Pedicle screw fixation for hangman's
      fracture of the axis and traumatic lesions of the middle and lower cervical spine
      has been reported; however, there have been no reports on pedicle screw fixation
      for nontraumatic lesions of the cervical spine. METHODS: Forty-five patients with
      nontraumatic lesions of the cervical spine underwent reconstructive surgery
      including pedicle screw fixation and fusion. Five patients underwent
      occipitocervical fixation for the lesion of the upper cervical spine, and one
      patient underwent separate occipitocervical fixation and cervicothoracic
      fixation. Cervical or cervicothoracic fixation was performed in 39 patients.
      Twenty-six of these patients underwent simultaneous laminectomy or laminoplasty.
      Supplemental anterior surgery was conducted for 15 patients. RESULTS: Solid
      fusion was obtained in all patients except eight with metastatic vertebral tumors
      who did not receive bone graft. Correction of kyphosis was adequate. There were
      no neurovascular complications, except one case of transient radiculopathy caused
      by screw threads. CONCLUSIONS: Pedicle screw fixation is a useful procedure for
      posterior reconstruction of the cervical spine. This procedure does not require
      the lamina for stabilization, and should be especially valuable for simultaneous
      posterior decompression and fusion. The risk to neurovascular structures,
      however, cannot be completely eliminated.

PMID- 9280022
TI  - Trunk extension strength and muscle activity in standing and kneeling postures.
AB  - STUDY DESIGN: A split-plot experimental design was used to evaluate the influence
      of posture, trunk angle, and rotational velocity on peak torque output and
      myoelectric activity during maximal trunk extension maneuvers. OBJECTIVES: To
      determine whether the kneeling posture alters extension torque capabilities in
      isometric and isokinetic exercises as compared with standing. Also, to ascertain
      whether recruitment of trunk muscles is modified by such a postural change.
      SUMMARY OF BACKGROUND DATA: Factors such as workplace geometry may force workers
      to adopt awkward or unusual postures in the performance of manual tasks. An
      understanding of the limitations placed on strength in unconventional working
      postures is crucial to the proper design of jobs. METHODS: Twenty-one healthy
      male subjects (mean age = 36 years +/- 7 SD) performed 12 trunk extension
      exertions in standing and kneeling postures. Isometric tests were performed at
      22.5 degrees, 45 degrees, and 67.5 degrees of trunk flexion. Isokinetic tests
      were done at three velocities: 30 degrees/sec, 60 degrees/sec, and 90
      degrees/sec. Electromyographic data were collected from eight trunk muscles to
      assess muscle recruitment under each condition. A priori orthogonal contrasts
      were specified for analysis of both torque and electromyographic data. RESULTS:
      The kneeling posture was associated with a 15% decrease in peak torque output
      when contrasted with standing: however, no concomitant change in trunk muscle
      activity was evident. Trunk hyperflexion (isometric tests) and increasing
      rotational velocity (isokinetic tests) were associated with reduced torque in
      both postures. Trunk muscle activity was primarily affected by changes in trunk
      angle and velocity of contraction. CONCLUSIONS: A reduced extensor capability
      exists in the kneeling posture, despite equivalent trunk muscle activity. The
      similar activation patterns in both postures suggest that the strength deficit
      does not result from alterations in trunk muscle function. Rather, it may be the
      consequence of a reduced capability to rotate the pelvis in the kneeling posture,
      due to a disruption of the biomechanical linkage of the leg structures.

PMID- 9280023
TI  - An electromyographic comparison of abdominal muscle synergies during curl and
      double straight leg lowering exercises with control of the pelvic position.
AB  - STUDY DESIGN: This prospective study evaluated the abdominal muscle activity
      during the Isometric bent knee curl and double straight leg lowering exercise.
      OBJECTIVES: To compare the magnitude of the electromyographic activity across the
      curl and double straight leg lowering exercise and determine if the muscle
      synergies were specific to a given exercise. SUMMARY OF BACKGROUND DATA:
      Abdominal muscle strengthening exercises are frequently recommended in the
      prevention and rehabilitation of individuals with low back pain. Previous studies
      comparing the curl exercise with the double straight leg lowering exercise did
      not support the notion that the double straight leg lowering exercise is more
      demanding on the abdominal muscles. No previous study examined these two
      exercises while maintaining a constant pelvic position. METHODS: Fifteen male
      subjects had the electromyographic activity of the rectus abdominis, the external
      oblique, and the internal oblique abdominal muscles evaluated during the curl and
      double straight leg lowering exercise. The same position of the posterior pelvic
      tilt was maintained between each exercise using feedback from an
      electrogoniometer attached to the pelvis. RESULTS: The double straight leg
      lowering exercise resulted in significantly greater activation of the abdominal
      muscles compared with the curl. Two abdominal muscle synergies emerged during the
      double straight leg lowering exercise: synergy I exhibited high rectus abdominis,
      high external oblique, and low internal oblique muscle activity, whereas synergy
      II exhibited low rectus abdominis, high external oblique, and high internal
      oblique. CONCLUSIONS: The results support the use of the double straight leg
      lowering with the posterior pelvic tilt for achieving greater abdominal muscle
      coactivation in an exercise program.

PMID- 9280024
TI  - Pain pattern in pregnancy and "catching" of the leg in pregnant women with
      posterior pelvic pain.
AB  - STUDY DESIGN: A cross-sectional study of symptoms and signs in pregnant women.
      OBJECTIVES: To describe the clinical appearance of back pain in pregnancy and the
      relation between pain distribution and symptoms in women with posterior pelvic
      pain, in order to shed light on etiologic factors. SUMMARY OF BACKGROUND DATA:
      Back pain is common in the general population. During pregnancy, it is even more
      common, and back pain is experienced by about 50% of pregnant women. In the
      pregnant woman, differentiation between common low back pain and posterior pelvic
      pain is believed to be essential because these symptoms should be treated in
      different ways. METHODS: The women were interviewed with a questionnaire. Those
      with back symptoms completed a pain drawing and were examined by an orthopedic
      surgeon. Based on the symptoms and findings, the women were divided into three
      groups: thoracic pain, lumbar pain, and posterior pelvic pain. RESULTS: Of 335
      pregnant women, 51% had back pain at the time of examination. The pain was more
      widespread compared with common low back pain. Seventy-one percent of the 171
      patients examined by the orthopedic surgeon had a positive posterior pelvic pain
      test. These women more often had pain in the gluteal and posterior thigh regions.
      A "catching" feeling of the leg was described when walking by 44 of 122 these
      women, whereas only 1 of 49 women without a posterior pelvic pain test had such
      symptoms. CONCLUSIONS: The higher prevalence of back pain in pregnancy may be due
      to several factors. In women with posterior pelvic pain, there is a specific
      symptom-a catching of the leg when walking. The most probable explanation for the
      catching is that local nociception disturbs muscular function in women with
      posterior pelvic pain because changes in the sacroiliac joint range of motion,
      which is very small, cannot cause this symptom.

PMID- 9280025
TI  - The intravertebral vacuum phenomenon ("vertebral osteonecrosis"). Migration of
      intradiscal gas in a fractured vertebral body?
AB  - STUDY DESIGN: Retrospective cohort. OBJECTIVES: To compare the prevalence of the
      association between contiguous intervertebral disc and vertebral collapses with
      or without an intravertebral vacuum phenomenon. SUMMARY OF BACKGROUND DATA: The
      mechanism of occasional gas accumulation within some vertebral collapses is
      poorly known. The current hypothesis is that this phenomenon is indicative of
      bone ischemia. In fact, avascular necrosis as the main pathologic event remains
      speculative, and should not explain per se the presence of gas within a vertebral
      body. METHODS: Comparison of the prevalence of intervertebral disc vacuum
      phenomenon adjacent to the affected vertebral body in 23 cases of intravertebral
      vacuum phenomenon in 19 patients (intravertebral vacuum phenomenon group) and in
      708 osteoporotic collapses without intravertebral vacuum phenomenon in 199
      patients (control group). RESULTS: There were no differences in sex and age
      between the two groups, and all the patients in the intravertebral vacuum
      phenomenon group had signs of underlying osteoporosis. A vacuum phenomenon in at
      least one intervertebral disc adjacent to the collapses on radiographs,
      conventional tomography, computed tomography, or magnetic resonance imaging was
      found in 19 cases (83%) in the intravertebral vacuum phenomenon group, compared
      with 13% in the control group (P < 0.0001). Considering plain radiographs only,
      this association was found in 50% of the intravertebral vacuum phenomenon group
      and in 9.7% of the control group (P < 0.0001). The intervertebral and
      intravertebral gaseous collections were connected through a fractured endplate in
      six cases. CONCLUSIONS: The high prevalence of the association of contiguous
      intervertebral and intravertebral vacuum phenomenon could have implications in
      the pathogenesis of the intravertebral vacuum phenomenon. We hypothesize that the
      intravertebral vacuum phenomenon could simply be the result of migration of an
      intradiscal-gaseous collection through the fractured endplate of some
      osteoporotic collapses.

PMID- 9280026
TI  - Postoperative pain control after lumbar spine fusion. Patient-controlled
      analgesia versus continuous epidural analgesia.
AB  - STUDY DESIGN: A prospective, randomized, double-blind clinical trial. OBJECTIVE:
      To compare the efficacy of postoperative continuous epidural analgesia versus
      patient-controlled analgesia in patients undergoing lumbar fusion. SUMMARY OF
      BACKGROUND DATA: Controversy remains regarding the optimal strategy for
      postoperative pain control. METHODS: Fifty-four patients were divided into two
      treatment groups. There was no difference between the groups with respect to age,
      levels fused, estimated blood loss, and use of spinal instrumentation. Patient
      controlled analgesia or epidural analgesia was administered in a double-blind
      manner for a 3-day postoperative course. Each patient received both an epidural
      and a patient-controlled analgesia delivery system; 26 received the epidural
      active agent and 28 received patient-controlled analgesia. Postoperative time to
      liquids and solid food, ambulation, length of stay, and side effects was
      recorded. Pain was evaluated by a visual analog scale on postoperative days 1, 2,
      and 3. RESULTS: Results showed no difference between the groups with reference to
      diet, ambulation, length of stay, and visual analog scale scores. Minor side
      effects occurred in 71% of patients in both groups. No major complications
      occurred. Epidural catheter dislodgment occurred in 11% of patients. The total
      cost for epidural analgesia was approximately $550 more than that for patient
      controlled analgesia for a 3-day postoperative course. CONCLUSIONS: These data
      suggest that there is no clinical advantage of epidural opiate/local anesthetic
      analgesia over systemic opiate by patient-controlled analgesia for spinal fusion
      patients. However, possible technical limitations (namely, the low dosage of
      bupivacaine and placement of the catheter tip) may have prevented adequate
      delivery of anesthetic to the involved segments. Although the incidence of side
      effects is similar, cost factors and a high incidence of epidural catheter
      dislodgment favor use of patient-controlled analgesia.

PMID- 9280027
TI  - Clinical analysis of two-level compression of the cauda equina and the nerve
      roots in lumbar spinal canal stenosis.
AB  - STUDY DESIGN: This study is a prospective, clinical study assessing the efficacy
      of selective decompression of the responsible level in two-level stenosis in
      accordance with neurologic findings defined by the gait load test, and functional
      diagnosis based on selective nerve root block. OBJECTIVE: To clarify the clinical
      features of two-level stenosis regarding the neurologic level responsible for the
      symptoms, neurogenic intermittent claudication, and the outcome of selective
      decompression. SUMMARY OF BACKGROUND DATA: Experimental studies have indicated
      that double-level compression of the cauda equina induces a more severe
      impairment of nerve function than does single-level compression. However, few
      studies have focused on the clinical importance of two-level stenosis. The
      clinical effects of two-level stenosis on the cauda equina and nerve roots are
      unknown. METHODS: A total of 81 patients with lumbar spinal canal stenosis due to
      spondylosis and degenerative spondylolisthesis were divided into two groups, two
      level stenosis at L3-L4 and L4-L5, and one-level stenosis at L4-L5, based on
      myelography. The types of neurogenic intermittent claudication, the level
      responsible for neurologic findings, and the postsurgical outcome were compared
      between both groups. The level responsible for the symptoms in two-level stenosis
      was determined in accordance with neurologic findings on the gait load test and
      functional diagnosis based on a selective nerve root block. All patients
      underwent a prospective, selective decompression at the neurologically
      responsible level only. The average follow-up period was 4.6 years (range, 1-8
      years). RESULTS: The patients with two-level stenosis more frequently had cauda
      equina symptoms than those with one-level stenosis, except patients with
      degenerative spondylolisthesis. It was therefore assumed that two-level stenosis
      was associated with cauda equina impairment, Changes in neurologic condition
      before and after the gait test were observed in four patients with two-level
      stenosis. Finally, for 28 patients with two-level stenosis, the levels
      responsible for the neurologic symptoms were the caudal level (L4-L5) in 22
      patients, the cranial level (L3-L4) in 1 patient, and both cranial and caudal
      levels (L3-L4 and L4-L5) in 5 patients. All stenotic levels on the myelogram were
      not always symptomatic in two-level stenosis. However, in one-level stenosis, all
      of the responsible levels completely corresponded to the myelogram. Selective
      decompression only at the neurologically responsible level improved neurogenic
      intermittent claudication in all patients. The asymptomatic levels at which the
      stenotic condition was left unchanged at surgery did not become symptomatic at
      follow-up; in addition, there was no significant difference in the postoperative
      outcome between two-level stenosis and one-level stenosis. CONCLUSIONS: Two-level
      stenosis in patients with lumbar spondylosis is associated with production of
      cauda equina lesions. The gait load test provides information regarding changes
      in symptoms and neurologic condition during exercise. The responsible levels
      should be determined based on neurologic findings after the gait load test and a
      selective nerve root block. It is uncommon for both stenotic levels to be
      symptomatic in patients with two-level stenosis. Less invasive surgery such as
      selective decompression for the responsible level in patients with two-level
      stenosis is a useful technique with a good potential for long-term success.

PMID- 9280028
TI  - Local spread of metastatic vertebral tumors. A histologic study.
AB  - STUDY DESIGN: Nineteen solitary metastatic vertebral tumors obtained by total en
      bloc spondylectomy were analyzed histologically. OBJECTIVES: To determine the
      mechanisms of local spread of vertebral tumors and identity barrier tissues to
      tumor progression in the vertebra. SUMMARY OF BACKGROUND DATA: Histologic studies
      of specimens resected at amputation or en bloc excision have determined the
      pattern of local spread of bone and soft tissue tumors in the extremities and
      identified barrier tissues to tumor spread. However, a similar assessment of
      vertebral malignancies is difficult. The development of total en bloc
      spondylectomy for primary vertebral malignancy and solitary has allowed the
      collection of tissue samples sufficient to analyze the pattern of local spread of
      tumors, using the concept of compartment and barrier. METHODS: Histologic
      sections of all vertebral elements were prepared from specimens collected after
      en bloc spondylectomy. Serial 5-mm sections in the sagittal plane were also
      prepared and examined. RESULTS: Analysis of tumor location showed that metastatic
      tumors reached the vertebral column by invading the bone marrow of the dorsal
      region of the vertebral body. The anterior longitudinal ligament, posterior
      longitudinal ligament, periosteum abutting the spinal canal, ligamentum flavum,
      periosteum of the lamina and spinous process, interspinous ligament, supraspinous
      ligament, cartilaginous endplate and the anulus fibrosus served as barriers to
      tumor progression. The posterior longitudinal ligament was the weakest barrier
      tissue and was gradually destroyed by the tumor at the point of perforating
      vessels. Even after destruction of the barrier tissue, tumor cells were covered
      with a thin, fibrous reactive membrane. Two pathways allowed tumor spread to the
      adjacent vertebrae: 1) from the edge of the vertebral body to the adjacent
      vertebral body beneath the longitudinal ligament, and 2) through the
      paravertebral muscles to the neighboring lamina. CONCLUSIONS: Each vertebra can
      be represented by a compartment surrounded by several barriers. The most common
      path for tumor spread is through the posterior longitudinal ligament to the
      epidural space.

PMID- 9280029
TI  - Intraoperative optoelectronic analysis of three-dimensional vertebral
      displacement after Cotrel-Dubousset rod rotation. A preliminary report.
AB  - STUDY DESIGN: This study analyzed intraoperatively the three-dimensional
      displacement of vertebrae during rotation of the Cotrel-Dubousset rod for
      scoliosis correction, using an optoelectronic method. OBJECTIVE: To evaluate
      three-dimensional transitions and rotations of instrumented and uninstrumented
      vertebrae, produced by the Cotrel-Dubousset instrumentation "derotation"
      maneuver. SUMMARY OF BACKGROUND DATA: Published reports indicate that Cotrel
      Dubousset instrumentation has been more effective in producing spinal derotation
      than vertebral axial derotation, but no study analyzed intraoperatively the
      effects on the vertebrae produced solely by rotation of the rod. METHODS: Eight
      patients with idiopathic scoliosis treated with Cotrel-Dubousset instrumentation
      underwent intraoperative optoelectronic monitoring using infrared cameras
      (Vicon). Markers were implanted in the spinous processes of the lower and upper
      instrumented vertebrae (LIV, UIV), the adjacent uninstrumented vertebrae below
      and above (-LIV, +UIV), and the apical vertebra. During rod rotation, acquisition
      and processing of cameras data were performed to obtain three-dimensional
      displacements of vertebrae. RESULTS: Translations and rotations of LIV and UIV
      were in identical directions to those of -LIV and +UIV, respectively. Orientation
      of the LIV hook influenced the displacement of LIV and -LIV. Posterior
      translation of the apical vertebra was commonly observed in thoracic King II,
      III, or V curvatures (apical vertebra = T9), and anterior translation in King I
      and IV and thoracolumbar curvatures (apical vertebra = T11-T12). Axial rotation
      of the apical vertebra was increased in thoracic curvatures and decreased in
      thoracolumbar and lumbar curvatures. Lateral translation was the major
      displacement observed. CONCLUSIONS: Rotation of the rod produces rotational and
      translational changes along each axis. These results are preliminary, but
      substantial. Technical improvement would allow more accurate results in the near
      future.

PMID- 9280030
TI  - Intermittent distracting rod for correction of high neurologic risk congenital
      scoliosis.
AB  - STUDY DESIGN: Report of three cases of severe congenital scoliosis corrected by a
      new device. OBJECTIVES: To show a new, safe alternative for treatment to achieve
      and maintain correction of the most severe spinal deformity. SUMMARY OF
      BACKGROUND DATA: Because of neurologic risk, severe congenital scoliosis is
      usually not instrumented. Gradual correction seems to be safer for the spinal
      cord and to produce more efficient results because of the viscoelastic properties
      of the spine. METHODS: A new device was used in three patients with congenital
      scoliosis. This device is placed by a posterior approach and permits correction
      of the scoliosis by slow, intermittent distraction. The gear of the elongation
      mechanism is activated by an extender placed subcutaneously. The correction takes
      place in the conscious patient, under rigorous neurologic control. RESULTS: At
      the end of the distraction procedure, corrections of the scolioses in the three
      patients were from 118 degrees to 45 degrees, 104 degrees to 47 degrees, and 137
      degrees to 71 degrees, respectively CONCLUSIONS: The new device has proved useful
      for correcting, efficiently and without neurologic damage, severe scoliosis in
      three patients, and may be helpful in those curves with high neurologic risk.

PMID- 9280031
TI  - Idiopathic avascular necrosis of a vertebral body. Case report and literature
      review.
AB  - STUDY DESIGN: Case report and literature review. OBJECTIVES: To review the
      English literature pertaining to idiopathic avascular necrosis of a vertebral
      body. As an illustrative example, the case of a 60-year-old woman with idiopathic
      avascular necrosis of L4 is presented. SUMMARY OF BACKGROUND DATA: Avascular
      necrosis of a vertebral body is an uncommon entity. Avascular necrosis has been
      described in the context of other underlying lesions, such as with malignancy,
      infection, radiation therapy, and systemic steroid treatment. The intravertebral
      vacuum cleft phenomenon seen on plain films has been strongly associated with
      vertebral body avascular necrosis. METHODS: Literature and chart review was
      carried out. Vertebral body avascular necrosis was initially identified with
      imaging studies and confirmed with biopsy. A comprehensive preoperative
      evaluation did not identify a specific cause of avascular necrosis. The patient
      underwent vertebral body resection with fibula allograft struts. CONCLUSIONS:
      Although vertebral body collapse in an osteoporotic individual is relatively
      common, a case is reported of vertebral body collapse and subsequent necrosis
      without evidence of underlying disease at 48-month follow-up. The current
      findings support the diagnosis of idiopathic avascular necrosis of L4.

PMID- 9280032
TI  - Fracture-dislocation at the thoracolumbar junction in an infant with locked
      vertebrae. A case report.
AB  - STUDY DESIGN: A retrospective, single-patient case report. OBJECTIVES: To report
      on a 9-month-old infant with fracture-dislocation at the thoracolumbar junction
      with locking of vertebral bodies, probably with incomplete neurologic injury and
      partial postoperative recovery. SUMMARY OF BACKGROUND DATA: Fracture-dislocation
      at the thoracolumbar junction is rare in infants, the upper cervical spine being
      the level usually affected. Incomplete neurologic injury is uncommon after such a
      severe shear injury. METHODS: The patient was followed through personal
      examination and chart review from initial presentation to 6 months after the
      injury. RESULTS: Open reduction with posterior spinal fusion was followed by
      partial neurologic recovery and a stable spine over 6-month follow-up.
      CONCLUSIONS: Fracture-dislocation at the thoracolumbar junction is rare in
      infancy. This is probably due to unique anatomic and biomechanical features of
      the spine in infancy.

PMID- 9280033
TI  - Bayesian interim analysis of phase II cancer clinical trials.
AB  - Many popular sequential phase II clinical trial designs optimize some criterion
      subject to constraints on the error probabilities at null and alternative values
      of the response rate. Such designs may forfeit optimality if one fails to conduct
      analyses strictly according to plan. Moreover, a decision, say, to accept the
      experimental therapy at one interim analysis does not necessarily imply the same
      degree of evidence as the same decision when made at another analysis. I propose
      an alternative design that bases decisions on the ability of the data to persuade
      either a sceptic or an enthusiast. My standard of evidence, called the persuasion
      probability, is based on the Bayesian posterior probability that the experimental
      treatment is superior to the standard. The design calls for termination at any
      interim analysis at which an observed persuasion probability exceeds its critical
      value. I investigate the standards of evidence implied by some frequentist
      procedures and calculate frequentist properties of persuasion-probability
      designs.

PMID- 9280034
TI  - A bayesian strategy for evaluating treatments applicable only to a subset of
      patients.
AB  - If we wish to evaluate the efficacy of a proposed treatment applicable only to a
      subset of the patient population, then a comparison of the results of the
      proposed treatment with historical experience may be misleading if the
      applicability of the proposed treatment is itself of prognostic value. We present
      a Bayesian strategy to estimate the response rate of patients eligible for the
      proposed treatment but who receive standard therapy; we can compare the results
      with the experimentally observed response rate of patients who receive the
      proposed therapy. I extend the approach to apply to time to event data that may
      be censored, such as time to disease progression. One can use the information
      obtained in this fashion to evaluate experimental designs for future trials of
      the proposed treatment.

PMID- 9280035
TI  - Grouped random effects models for Bayesian meta-analysis.
AB  - Meta-analysis refers to quantitative methods to combine results from independent
      studies so as to draw overall conclusions. Frequently, results from dissimilar
      studies are inappropriately combined, resulting in suspect inferential synthesis.
      We present a straightforward method to identify and address this problem through
      the development of grouped random effect models for meta-analysis. We examine 15
      comparative studies that investigate the efficacy of a new anti-epileptic drug,
      progabide. The flexibility of this modelling scheme is exemplified by the result
      that the open studies support the efficacy of progabide while the closed studies
      support the reverse hypothesis. Bayesian approaches for meta-analysis are
      preferable because of the small number of studies prevalent in meta-analysis. We
      specify diffuse proper prior and hyperprior distributions to assure posterior
      propriety. We investigate sensitivity of the posterior to choice of prior. We use
      Gibbs sampling and the Metropolis algorithm to generate samples from the relevant
      posteriors. We analyse posterior summaries and plots of model parameters to
      suggest solutions to questions of interest.

PMID- 9280036
TI  - On a non-proportional hazards regression model for repeated medical random
      counts.
AB  - A wholly parametric non-proportional hazards survival model is introduced. The
      model retains Cox's constant of proportionality as the leading term in the
      relative risk but permits additional flexibility by modelling the relative risk
      as a function of time. Covariate effects are modelled on the log odds scale, a
      choice which is more in keeping with the spirit of the multiple logistic
      function, rather than on the logarithmic scale, as in the proportional hazards
      model. Some basic properties of the model are described. A special feature of the
      model is that, when the proportional hazards model applies, Cox's regression
      coefficients are easily recovered and the computation of other time dependent
      quantities of interest is routine. A semi-Markov version of the model is derived
      to analyse recurrent sequential state processes and this is applied to a study of
      valvotomies conducted in the Regional Medical Cardiology Centre in Belfast,
      Northern Ireland. The results obtained are compared with those from the classical
      proportional hazards analysis.

PMID- 9280037
TI  - A truncated poisson regression model with applications to occurrence of
      adenomatous polyps.
AB  - Adenomatous polyps are considered as the dominant precursor lesion of colorectal
      cancer. A phase III colorectal cancer prevention trial, conducted by the Arizona
      Cancer Center, concerns the ability of wheat bran fibre supplement to reduce the
      recurrence of adenomatous polyps. All participants in the study are to have had
      colorectal polyps detected and removed during a baseline (qualifying) colonoscopy
      within three months prior to enrolment. In this paper, our interest focuses on
      occurrence of adenomatous polyps at the baseline colonoscopy. We use a truncated
      Poisson model to fit these types of data. We develop a regression model to assess
      the effects of explanatory factors on the positive counting variable. We fit
      truncated Poisson parameters by a log-linear regression model and estimate
      regression parameters by the maximum likelihood procedure. Finally, we apply it
      to the baseline colonoscopy data from the Wheat Bran Fiber study.

PMID- 9280038
TI  - A test of missing completely at random for longitudinal data with missing
      observations.
AB  - Liang and Zeger proposed a generalized estimating equations approach to the
      analysis of longitudinal data. Their models assume that missing observations are
      missing completely at random in the sense of Rubin. However, when this assumption
      does not hold, their analysis may yield biased results. In this paper, we develop
      a simple and practical procedure for testing this assumption. The proposed
      procedure is related to that of Park and Davis.

PMID- 9280040
TI  - Comparative calibration without a gold standard.
AB  - Comparative calibration is the broad statistical methodology used to assess the
      calibration of a set of p instruments, each designed to measure the same
      characteristic, on a common group of individuals. Different from the usual
      calibration problem, the true underlying quantity measured is unobservable. Many
      authors have shown that this problem, in general, does not have a unique
      solution. Most commonly used assumptions to obtain a unique solution are (i) one
      instrument is the gold standard (that is, unbiased) and (ii) the measurement
      errors of the p instruments are independent. Such constraints, however, may not
      be valid for many clinical applications, for example, the universal
      standardization project for dual X-ray absorptiometry (DXA) scanners. In this
      paper, we propose a new approach to resolve the comparative calibration problem
      when a gold standard is unavailable. Instead of the usual assumptions, we use
      external information in addition to data from the p instruments, to solve the
      problem. We address statistical estimation, hypothesis testing and missing data
      problems. We apply the new method specifically to the universal standardization
      project data where a group of individuals have been measured for bone mineral
      density (BMD) by three DXA scanners. We compare the results of the new method to
      currently used methods and show that they have better statistical properties.

PMID- 9280041
TI  - Natural scrapie and PrP genotype: case-control studies in British sheep.
AB  - Natural scrapie in sheep is associated with polymorphisms of the PrP gene,
      particularly at amino acid codons 136, 154 and 171. This paper reports the
      results of nine scrapie case-control studies in Bleu du Maine, Herdwick, Merino x
      Shetland, Poll Dorset, Scottish Halfbred, Shetland, Soay, Suffolk and Swaledale
      sheep from British flocks affected by scrapie. In some outbreaks, scrapie was
      found to occur only in animals with at least one PrP allele encoding valine at
      codon 136 (V136), usually a relatively rare allele in healthy controls. In other
      outbreaks, the V136, PrP allele was either not found or was not an absolute
      prerequisite for scrapie to develop. Although scrapie had a strong tendency to
      affect sheep with PrP genotypes homozygous for glutamine at codon 171 (QQ171),
      these genotypes (QQ171 but varying at other codon positions) were relatively
      common in healthy controls. The reliable prediction of scrapie susceptibility in
      previously uninvestigated sheep flocks will therefore require information at
      least about PrP genotypes at codons 136 and 171.

PMID- 9280039
TI  - Clustering of leukaemia cases in a city in Israel.
AB  - A temporal cluster of cases may result from exposure to a new carcinogen, but it
      may also occur under stable conditions or as result of another factor, such as
      changes in medical practice. In this study, we used several complementary methods
      to detect a cluster and to conduct an initial investigation regarding its cause.
      The analyses included three stages, and were based on the time interval between
      consecutive diagnoses. First, we applied the sets monitoring technique to detect
      clustering. Following the detection (alarm), a confirmatory analysis was
      conducted in order to confirm or refute it as a true alarm. We applied this
      analysis to the first five cases diagnosed subsequent to the alarm. With a
      graphical display of the temporal pattern of the diagnoses, we considered the
      possible causes leading to the cluster. The data included registered diagnoses of
      leukaemia cases made from 1960 to 1990 among residents of Ashkelon, Israel.
      Clustering was detected for acute lymphatic leukaemia and for chronic myeloid
      leukaemia. We found that the temporal patterns of the diagnoses consistent with
      the possibility that these two clusters are due to exposure to a common local
      carcinogen. We cannot however, rule out the possibility that these clusters are
      due to unknown factors.

PMID- 9280042
TI  - Comparison of three injectable anaesthetic techniques in pigs.
AB  - Forty-six near-adult pigs (mean age 10 months, mean weight 156 kg) were
      anaesthetised for laparoscopy. After intramuscular azaperone (1.0 mg/kg) and
      ketamine (2.5 mg/kg), 14 of the pigs received intravenous etomidate (200
      micrograms/kg) and midazolam (100 micrograms/kg) and 17 were given ketamine (2
      mg/kg) and midazolam (100 micrograms/kg). The other 15 pigs were anaesthetised
      with pentobarbitone (15 to 20 mg/kg) without pre-anaesthetic medication. The
      duration and adequacy of anaesthesia, recovery rate, and seven physiological
      variables (ECG, heart rate, indirect arterial blood pressure, respiratory rate,
      minute volume, mean end-tidal carbon dioxide concentration and percentage oxygen
      saturation of haemoglobin) were compared. Repeated injections were needed in 29
      of the 46 cases. Pentobarbitone was the least satisfactory drug because although
      the haemodynamic variables were greater, it caused more respiratory depression
      and a higher overall complication rate than the other methods. Apnoea occurred in
      two pigs, and was fatal in one, and positive pressure ventilation with oxygen was
      needed in three others. Intubation conditions were poorer and the times to
      standing, walking and rooting were longer in the pigs anaesthetised with
      pentobarbitone.

PMID- 9280043
TI  - Septic tenosynovitis and focal osteomyelitis of the lateral proximal sesamoid
      bone in a thoroughbred gelding.
AB  - Chronic septic tenosynovitis with concurrent, associated focal osteomyelitis of
      the lateral proximal sesamoid bone was diagnosed in a seven-year-old thoroughbred
      gelding. Surgical management of this case consisted of open annular ligament
      desmotomy and curettage of the affected sesamoid. Following lavage of the digital
      sheath the incisional wound was closed but a 2 cm gap was left distally to allow
      for postoperative open drainage. The distal limb was bandaged and the horse
      treated with antibiotics and non-steroidal anti-inflammatories. Sepsis resolved
      and the horse made a gradual return to full work.

PMID- 9280044
TI  - Outbreak of severe fatal orf in lambs.

PMID- 9280045
TI  - Thromboarteritis of a patent ductus arteriosus and pulmonary artery in a four
      year-old cow.

PMID- 9280046
TI  - Rabies and quarantine.

PMID- 9280047
TI  - Quantifying CPD.

PMID- 9280048
TI  - Systematic application of ESWL and percutaneous nephrolithotomy.

PMID- 9280049
TI  - The role of the papilla in idiopathic calcium oxalate nephrolithiasis.
AB  - The complex and multifactorial phenomenon of urinary stone disease remains
      unclear. Anatomical and physiochemical theories do not adequately deal with
      certain aspects of idiopathic calcium oxalate nephrolithiasis in particular or of
      nephrolithiasis. One of the reasons for this could be that nephrolithiasis is not
      only a primary disorder but may also be a symptom of other disorders or various
      pathologic changes in the metabolism of lithogenic substances. Both affirmative
      and contradictory reports have been published since Randall's first description
      of papillary calcifications and their possible active role in the genesis of
      calcium oxalate nephrolithiasis. Our intention is to discuss focal calcified
      lesions as an etiologic factor of renal stone disease as well as the change from
      historical to modern concepts regarding the development of medullary
      calcifications and their relationship to idiopathic calcium oxalate
      nephrolithiasis.

PMID- 9280050
TI  - Intratubular crystallization events.
AB  - Can urolithiasis start as an intratubular event? Under severe hyperoxaluric
      conditions in animal models at least crystal formation can. Recently models have
      been presented that assess the chances of crystal formation under more normal
      conditions. These models describe changes in fluid composition as this passes
      through the nephron, these conditions being simulated in in vitro experiments. It
      appears that under naturally occurring intratubular conditions calcium-salt
      crystallization takes place within the time tubular fluid normally spends in the
      nephron. Precipitation starts with a calcium-phosphate phase under conditions
      found in the thin lambs. This crystalline phase then (partly) dissolves when
      collecting duct conditions are used, thereby inducing formation of calcium
      oxalates. Under these conditions the latter increase in size by way of crystal
      growth and agglomeration. Large particle formation and cell adhesion can
      eventually result in particle retention and subsequent stone formation. Viewing
      urolithiasis as originally an intratubular event has consequences for in vitro
      experiments and treatments, which are discussed in this paper.

PMID- 9280051
TI  - Cell cultures and nephrolithiasis.
AB  - While the physical chemistry of stone formation has been intensively studied
      during the last decade, it has become clear that the pathophysiology of renal
      stone disease cannot be explained by crystallization processes only. In recent
      years, evidence has emerged that the cells lining the renal tubules can have an
      active role in creating the conditions under which stones may develop. Since it
      is difficult to study these mechanisms in vivo, cultured renal tubular cells have
      become increasingly popular for the study of physiological and cell biological
      processes that are possibly linked to stone disease. In this paper, we discuss
      the possible contribution of cellular processes such as transepithelial oxalate
      transport and crystal--cell interaction to the formation of renal stones.
      Experimental studies that have been performed with cultured renal cells to
      elucidate the mechanisms involved in these processes will be summarized.

PMID- 9280052
TI  - Animal models of kidney stone formation: an analysis.
AB  - Calcific kidney stones in both humans and mildly hyperoxaluric rats are located
      on renal papillary surfaces and consist of an organic matrix and crystals of
      calcium oxalate and/or calcium phosphate. The matrix is intimately associated
      with the crystals and contains substances that can promote as well as inhibit
      calcification. Osteopontin, Tamm-Horsfall protein, bikunin, and prothrombin
      fragment 1 have been identified in matrices of both human and rat stones.
      Hyperoxaluria can provoke calcium oxalate nephrolithiasis in both humans and
      rats. Kidney-stone-forming rats are hypomagnesuric and hypocitraturic during
      nephrolithiasis. Human stone formers may have the same disorders. Males of both
      species are prone to develop calcium oxalate nephrolithiasis, whereas females
      tend to form calcium phosphate stones. Oxalate metabolism is considered to be
      almost identical between rats and humans. Thus, there are many similarities
      between experimental nephrolithiasis induced in rats and human kidney-stone
      formation, and a rat model of calcium oxalate nephrolithiasis can be used to
      investigate the mechanisms involved in human kidney stone formation.

PMID- 9280053
TI  - In vitro crystallisation systems for the study of urinary stone formation.
AB  - Various methods and techniques are aimed at modelling crystallisation processes
      of urinary stone formation in vitro. There are considerable differences between
      them in technical and physico-chemical principles, quantification of crystal
      nucleation, growth and agglomeration and the parameters measured. In this paper,
      some important in vitro systems are described as examples. They are compared with
      regard to some of their features and capabilities. Emphasis has been placed on
      evaluation of the physiological relevance of the methods. For that reason, the
      different in vitro models have been related to current views on intrarenal in
      vivo, mechanisms underlying stone formation and other independent experimental
      results. Crystallisation procedures carried out in aqueous solutions are likely
      to mimic crystalluria, corresponding to a free-particle mechanism. However, a
      specifically tailored flow technique of crystallisation in gels seems to be a
      reasonable model of stone formation, in accordance with the generally accepted
      fixed-particle theory.

PMID- 9280054
TI  - Iridium 192 high-dose-rate brachytherapy--a useful alternative therapy for
      localized prostate cancer?
AB  - We report on a novel protocol involving iridium 192 high-dose-rate brachytherapy
      and follow-up of up to 130 months in patients with prostatic carcinoma. Using
      regional anesthesia, five to seven hollow needles are placed within the prostate
      by perineal puncture under ultrasound guidance. A 9-Gy prostate dose is applied
      followed by 30 min of hyperthermia (since 1991). This treatment is repeated once
      after 7 days; 2 weeks later, 18 x 2-Gy external beam radiation (small-field
      prostate) is added as percutaneous dose saturation. Since 1984 we have treated 40
      patients with this protocol. Local tumor control was achieved by means of
      prostatic biopsy at 18 months after therapy and determination of prostate
      specific antigen (PSA) values in about 70% of the patients; after a mean follow
      up period of more than 6 years (16-130 months), 80% of the patients show either
      no evidence of disease or stable disease. We therefore conclude that iridium 192
      high-dose-rate brachytherapy is a useful alternative in the treatment of
      localized prostate cancer in patients who are not eligible for radical
      prostatectomy.

PMID- 9280055
TI  - Can prostate-specific antigen reverse transcriptase-polymerase chain reaction be
      used as a prospective test to diagnose prostate cancer?
AB  - The present study addressed the question as to whether prostate-specific antigen
      reverse transcriptase-polymerase chain reaction (PSA RT-PCR) could be used to
      identify prospectively men who have prostate cancer and to help determine which
      patients with an initially negative biopsy would benefit from rebiopsy. PSA RT
      PCR was performed prospectively on 90 patients who were to have a prostate biopsy
      because of an elevated PSA level, an abnormal digital rectal examination, or
      both. PSA RT-PCR was performed, and the sensitivity of the test was enhanced by
      hybridization of the PCR with a 32P-labeled PSA cDNA probe (exons 3-5). Of the 90
      men, 36 (40%) had prostate cancer on biopsy. Of these 36 men, 5 (13.9%) had a
      positive PSA RT-PCR finding, whereas 31 (84.1%) tested negative. Of 54 men with
      negative biopsies, 8 (14.8%) had a positive PSA RT-PCR result. The sensitivity of
      PSA RT-PCR for the detection of biopsy-proven prostate cancer was 13.9% and the
      specificity was 85.2%. Only 3 of 12 (25%) patients with advanced disease had a
      positive test result. The sensitivity of PSA RT-PCR for the detection of biopsy
      proven prostate adenocarcinoma in men suspected of having prostate cancer is
      poor. Indeed, men without biopsy-proven prostate cancer are just as likely to
      have a positive result in the PSA RT-PCR as are men with cancer. Whether these
      men with negative prostate biopsies and positive PSA RT-PCR findings may
      eventually develop prostate cancer remains to be determined. At this time, PSA RT
      PCR for the prospective detection of prostate cancer should be considered
      investigational.

PMID- 9280056
TI  - Urodynamic abnormalities in two brothers with adrenomyeloneuropathy.
AB  - Adrenoleukodystrophy is an X-linked disorder characterized by loss of adrenal
      function and demyelinating nervous disease. A slowly progressive form,
      adrenomyeloneuropathy, has been described that can mimic multiple sclerosis. Two
      brothers are presented whose contrasting urodynamic findings are compatible with
      upper and mixed (upper and lower) motor neuron disease, respectively.

PMID- 9280057
TI  - The dynamics of the transcriptional response to cyclic adenosine 3',5'
      monophosphate: recurrent inducibility and refractory phase.
AB  - Activation of the cAMP signal transduction pathway results in the transcriptional
      induction of many genes. Several of them are induced with kinetics characteristic
      of the early response. One of these, the cAMP response element modulator (CREM)
      gene, is cAMP-inducible by virtue of an intronic promoter that directs the
      synthesis of the dominant negative inducible cAMP early repressor (ICER). ICER is
      involved in the down-regulation of its own promoter via an autoregulatory loop.
      Thus, while phosphorylation of cAMP response element binding protein (CREB) by
      the cAMP-dependent protein kinase A is the prerequisite for induction, it has
      been proposed that the following attenuation involves both CREB dephosphorylation
      and repression by the inducible repressor ICER. Here we show that ectopic
      expression of sense or antisense ICER in corticotroph AtT20 cells dramatically
      modifies the normal CREM inducibility profile. We have investigated the kinetics
      of CREM inducibility by recurrent stimulation of the cAMP-signaling pathway. We
      define the presence of a refractory phase that follows the first induction cycle.
      Accumulation of cAMP, protein kinase A activity, CREB/CREM phosphorylation, and
      ICER levels contribute to the refractory period. Strikingly, the length of the
      refractory period is determined by the length of the stimulation by cAMP
      responsible for the first cycle of induction.

PMID- 9280058
TI  - Ectopic ICER expression in pituitary corticotroph AtT20 cells: effects on
      morphology, cell cycle, and hormonal production.
AB  - The products of the cAMP response element modulator (CREM) gene play an important
      role in the transcriptional response to cAMP in endocrine cells. By virtue of an
      alternative, intronic promoter within the gene, the inducible cAMP early
      repressor (ICER) isoform is generated. ICER was shown to act as a dominant
      negative regulator and to be cAMP-inducible in various neuroendocrine cells and
      tissues. ICER negatively autoregulates its own expression and has been postulated
      to participate in the molecular events governing oscillatory hormonal
      regulations. To elucidate ICER function in pituitary physiology, we have
      generated AtT20 corticotroph cell lines expressing the sense or antisense ICER
      transcript under the control of the cadmium-inducible human methallothionein IIA
      promoter. Here we demonstrate that changes in the regulated levels of ICER have
      drastic consequences on the physiology of the corticotrophs. Ectopic ICER
      expression induces remarkable modifications in AtT20 morphology. Cells with
      persistent, nonregulated high levels of ICER are blocked in the G2/M phase of the
      cell cycle, while the opposite effect is obtained in cells expressing an
      antisense ICER transcript. We show that the effect of ICER on the AtT20 cell
      cycle is correlated to a direct down-regulation of the cyclin A gene promoter by
      ICER. Finally, we show that ACTH hormonal secretion from the corticotrophs is
      completely blocked by ICER ectopic expression. Interestingly, this effect is not
      due to a direct regulation of the POMC gene, but is mediated by a transcriptional
      control of the prohormone convertase 1 gene. These results point to a key
      regulatory function of CREM in pituitary physiology.

PMID- 9280059
TI  - Expression of the parathyroid hormone-related peptide gene in retinoic acid
      induced differentiation: involvement of ETS and Sp1.
AB  - Differentiation of P19 embryonal carcinoma (EC) and embryonal stem (ES)-5 cells
      with retinoic acid (RA) induces expression of PTH-related peptide (PTHrP) mRNA.
      In this study we have characterized a region between nucleotide (nt) -88 and -58
      relative to the transcription start site in the murine PTHrP gene that was
      involved in this expression. Sequence analysis identified two partially
      overlapping binding sites for the Ets family of transcription factors and an
      inverted Sp1-binding site. Two major specific bands were detected in a bandshift
      assay using an oligonucleotide spanning nt -88 and -58 as a probe and nuclear
      extracts from both undifferentiated and RA-differentiated P19 EC cells. The lower
      complex consisted of Ets-binding proteins as demonstrated by competition with
      consensus Ets-binding sites, while the upper complex contained Sp1-binding
      activity as demonstrated by competition with consensus Sp1-binding sites. The
      observed bandshift patterns using nuclear extracts of undifferentiated or RA
      differentiated P19 cells were indistinguishable, suggesting that the
      differentiation-mediated expression was not caused by the induction of expression
      of new transcription factors. Mutations in either of the Ets-binding sites or the
      Sp1-binding site completely abolished RA-induced expression of PTHrP promoter
      reporter constructs, indicating that the RA effect was dependent on the
      simultaneous action of both Ets- and Sp1-like activities. Furthermore, these
      mutations also abolished promoter activity in cells that constitutively expressed
      PTHrP mRNA, suggesting a central role for the Ets and Sp1 families of
      transcription factors in the expression regulation of the mouse PTHrP gene.

PMID- 9280060
TI  - The short form of the prolactin (PRL) receptor silences PRL induction of the beta
      casein gene promoter.
AB  - The PRL receptor (PRLR) is a member of the cytokine receptor superfamily. Rats
      and mice express two forms of PRLR, short (SPRLR) and long (LPRLR), which differ
      in the length and sequence of their cytoplasmic domains. We have analyzed the
      ability of each form of rat PRLR to transduce lactogenic signals in a bovine
      mammary gland epithelial cell line. The rat PRLR forms were expressed and
      detected by RT-PCR, indirect immunofluorescence, and cell surface ligand binding.
      When the biological activity of each form of PRLR was assessed by transient
      transfection, we found that the long form was able to activate the beta-casein
      gene promoter and that the short form was inactive. Interestingly, the
      coexpression of both forms of PRLR resulted in a block of PRL signal to the milk
      protein gene promoter as a function of the concentration of the SPRLR. Similar
      results were obtained when LPRLR was coexpressed with totally or partially
      inactive tyrosine mutants of either the Nb2 form or the LPRLR form. Thus, these
      results suggest that the SPRLR form has at least one clear biological function,
      i.e. to silence lactogenic signals and to contribute to a differential and acute
      PRL effect in rat tissues. Furthermore, the data derived from coexpression of
      LPRLR and PRLR mutants confirm a crucial role of the C-terminal tyrosine residue
      in lactogenic signaling and the dimerization of PRLRs.

PMID- 9280061
TI  - Identification of a novel sonic hedgehog response element in the chicken
      ovalbumin upstream promoter-transcription factor II promoter.
AB  - Sonic hedgehog (Shh) is a secreted morphogen that regulates dorso-ventral
      patterning within the neural tube during embryonic development. It is well
      established that Shh can induce motor-neuron differentiation that coincides with
      the appearance of specific motor-neuron markers including chicken ovalbumin
      upstream promoter-transcription factor II (COUP-TFII) and Isl1. However, the
      mechanism of Shh-induced signaling pathway in vertebrates is not clearly defined.
      In this report we have identified COUP-TFII as a target gene for Shh. In addition
      we have used a 1.6-kb region of the COUP-TFII promoter to identify a target
      element that mediates the Shh-induced activity. Extensive deletions introduced
      within this region have further enabled us to identify a novel sonic hedgehog
      response element (ShhRE) in the COUP-TFII promoter. Point mutations introduced
      within the ShhRE reveal some key nucleotides that are essential for protein(s)
      binding activity. Finally, the ShhRE is capable of functioning as a true enhancer
      element and can mediate Shh-induced transactivation of reporter gene via a
      heterologous promoter.

PMID- 9280062
TI  - Involvement of the transcription factor IID protein complex in gene activation by
      the N-terminal transactivation domain of the glucocorticoid receptor in vitro.
AB  - HeLa cell nuclear extracts were used to study the mechanism of activation of RNA
      polymerase II-mediated transcription by the N-terminal transactivation domain
      (tau1) of the glucocorticoid receptor in vitro. When fused to the Gal4 DNA
      binding domain, the tau1 domain activated transcription approximately 9-fold in
      HeLa nuclear extracts. Using heat treatment to inactivate transcription factor
      IID (TFIID) in the extract, it was shown that the addition of purified TFIID
      complex, but not the TATA-binding protein alone, was sufficient to restore this
      level of activation. The tau1 domain was shown to interact directly with the
      TFIID complex. This interaction was markedly reduced by a mutation in the tau1
      domain that reduces its activity. Furthermore, the interaction was specific for
      the TFIID complex, since no interaction was seen with TFIIIB, an analogous
      protein complex involved in RNA polymerase III transcription. The tau1 domain was
      further shown to interact with the TATA-binding protein subunit of the TFIID
      complex. These results suggest a mechanism by which the GR tau1 domain might
      contribute to gene activation by recruitment of the TFIID complex to target
      promoters.

PMID- 9280063
TI  - Point mutation in the ligand-binding domain of the progesterone receptor
      generates a transdominant negative phenotype.
AB  - A short conserved alpha-helix in the carboxyl-terminal activation function of the
      ligand-binding domain of steroid hormone receptors, called AF2, is important for
      ligand-dependent transactivation of inducible genes. We have generated two AF2
      mutants of the B isoform of human progesterone receptor (PRB): a point mutant,
      PRBE911A, and a short deletion, PRB delta907-913R. The two mutants are expressed
      at levels comparable to the wild type receptor in transfected cells. The PRBE911A
      mutant showed similar hormone- and DNA- binding affinities as the wild type
      receptor, whereas the PRB delta907-913R mutant was defective in hormone and DNA
      binding. Both mutants were inactive when transiently transfected in CV-1 cells,
      which do not express endogenous PR. However, the point mutant, but not the
      deletion mutant, inhibited transactivation by cotransfected wild type PRB in a
      hormone-dependent fashion. The activity of endogenous PR in T47D cells or of
      endogenous glucocorticoid receptor in HeLa cells was also inhibited by the
      PRBE911A, but not by the deletion mutant. The point mutant was less active when
      introduced into an N-terminal truncated form of PR, where it gave rise to
      proteins that formed homodimers with poor affinity for DNA, but were able to form
      heterodimers with PRB. The negative dominant phenotype of the PRBE911A mutant
      likely originates from competition with wild type receptors for binding to DNA
      and will be useful for mechanistic studies of receptor function.

PMID- 9280064
TI  - Mouse estrogen receptor beta forms estrogen response element-binding heterodimers
      with estrogen receptor alpha.
AB  - The recent discovery that an additional estrogen receptor subtype is present in
      various rat tissues has advanced our understanding of the mechanisms underlying
      estrogen signaling. Here we report on the cloning of the cDNA encoding the mouse
      homolog of estrogen receptor-beta (ER beta) and the functional characterization
      of mouse ER beta protein. ER beta is shown to have overlapping DNA-binding
      specificity with that of the estrogen receptor-alpha (ER alpha) and activates
      transcription of reporter gene constructs containing estrogen-response elements
      in transient transfections in response to estradiol. Using a mammalian two-hybrid
      system, the formation of heterodimers of the ER beta and ER alpha subtypes was
      demonstrated. Furthermore, ER beta and ER alpha form heterodimeric complexes with
      retained DNA-binding ability and specificity in vitro. In addition, DNA binding
      by the ER beta/ER alpha heterodimer appears to be dependent on both subtype
      proteins. Taken together these results suggest the existence of two previously
      unrecognized pathways of estrogen signaling; I, via ER beta in cells exclusively
      expressing this subtype, and II, via the formation of heterodimers in cells
      expressing both receptor subtypes.

PMID- 9280065
TI  - Transcriptional repression of the alpha-subunit gene by androgen receptor occurs
      independently of DNA binding but requires the DNA-binding and ligand-binding
      domains of the receptor.
AB  - The pituitary glycoprotein hormones LH and FSH regulate the reproductive cycle
      and are sensitive to feedback by gonadal steroids. The common alpha-subunit
      shared by these hormones is transcriptionally repressed by androgen receptor (AR)
      in the presence of its ligand dihydrotestosterone. This identifies at least one
      mechanism that contributes to AR-dependent suppression of gonadotropin synthesis.
      Repression of alpha-subunit transcription by AR requires only the sequences
      within the first 480 bp of the promoter. While this region contains a high
      affinity binding site for AR, this element does not mediate the suppressive
      effects of androgens. Instead, two other elements within the promoter-regulatory
      region (alpha-basal element and cAMP-regulatory element), which are important for
      expression of the alpha-subunit gene in gonadotropes, mediate the effects of AR.
      This suggests that AR inhibits activity of the alpha-subunit promoter by
      interfering with the transcriptional properties of the proteins that bind to
      alpha-basal element and the cAMP-regulatory elements. Furthermore, transfection
      analysis of various mutant ARs identified both the DNA-binding and ligand-binding
      domains of the receptor as critical for repression. Comparisons with the MMTV
      promoter revealed distinct structural requirements that underlie the
      transactivation and transrepression properties of AR.

PMID- 9280066
TI  - Evidence for ligand-dependent intramolecular folding of the AF-2 domain in
      vitamin D receptor-activated transcription and coactivator interaction.
AB  - A ligand-dependent transcriptional activation domain (AF-2) exists in region E of
      the nuclear receptors. This highly conserved domain may contact several
      coactivators that are putatively involved in nuclear receptor-mediated
      transcription. In this study, a panel of vitamin D receptor (VDR) AF-2 mutants
      was created to examine the importance of several conserved residues in VDR
      activated transcription. Two AF-2 mutants (L417S and E420Q) exhibited normal
      ligand binding, heterodimerization with retinoid X receptor, and vitamin D
      responsive element interaction, but they were transcriptionally inactive in a VDR
      responsive reporter gene assay. All AF-2 mutations that abolished VDR-mediated
      transactivation also eliminated interactions between VDR and several putative
      coactivator proteins including suppressor of gal1 (SUG1), steroid hormone
      receptor coactivator-1 (SRC-1), or receptor interacting protein (RIP140),
      suggesting that coactivator interaction is important for AF-2-mediated
      transcription. In support of this concept, the minimal AF-2 domain [VDR(408-427)]
      fused to the gal4 DNA binding domain was sufficient to mediate transactivation as
      well as interaction with putative coactivators. Introducing the L417S and E420Q
      mutations into the minimal AF-2 domain abolished this autonomous transactivation
      and coactivator interactions. Finally, we demonstrate that the minimal AF-2
      domain interacted with an AF-2 deletion mutant of the VDR in a 1,25-(OH)2D3
      dependent manner, suggesting a ligand-induced intramolecular folding of the VDR
      AF-2 domain. The L417S mutant of this domain disrupted the interaction with VDR
      ligand-binding domain, while the E420Q mutant did not affect this interaction.
      These studies suggest that the conserved AF-2 motif may mediate transactivation
      through ligand-dependent intermolecular interaction with coactivators and through
      ligand-induced intramolecular contacts with the VDR ligand-binding domain itself.

PMID- 9280067
TI  - Comparison of 6-s-cis- and 6-s-trans-locked analogs of 1alpha,25-dihydroxyvitamin
      D3 indicates that the 6-s-cis conformation is preferred for rapid nongenomic
      biological responses and that neither 6-s-cis- nor 6-s-trans-locked analogs are
      preferred for genomic biological responses.
AB  - The hormone 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] generates biological
      responses via both genomic and rapid, nongenomic mechanisms. The genomic
      responses utilize signal transduction pathways linked to a nuclear receptor
      (VDRnuc) for 1alpha,25(OH)2D3, while the rapid responses are believed to utilize
      other signal transduction pathways that may be linked to a putative membrane
      receptor for 1alpha,25(OH)2D3. The natural seco steroid is capable of facile
      rotation about its 6,7 single carbon bond, which permits generation of a
      continuum of potential ligand shapes extending from the 6-s-cis (steroid like) to
      the 6-s-trans (extended). To identify the shape of conformer(s) that can serve as
      agonists for the genomic and rapid biological responses, we measured multiple
      known agonist activities of two families of chemically synthesized analogs that
      were either locked in the 6-s-cis (6C) or 6-s-trans (6T) conformation. We found
      that 6T locked analogs were inactive or significantly less active than
      1alpha,25(OH)2D3 in both rapid responses (transcaltachia in perfused chick
      intestine, 45Ca2+ influx in ROS 17/2.8 cells) and genomic (osteocalcin induction
      in MG-63 cells, differentiation of HL-60 cells, growth arrest of MCF-7 cells,
      promoter transfection in COS-7 cells) assays. In genomic assays, 6C locked
      analogs bound poorly to the VDRnuc and were significantly less effective than
      1alpha,25(OH)2D3 in the same series of assays designed to measure genomic
      responses. In contrast, the 6C locked analogs were potent agonists of both rapid
      response pathways and had activities equivalent to the conformationally flexibile
      1alpha,25(OH)2D3; this represents the first demonstration that 6-s-cis locked
      analogs can function as agonists for vitamin D responses.

PMID- 9280068
TI  - Insulin-induced mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1)
      attenuates insulin-stimulated MAP kinase activity: a mechanism for the feedback
      inhibition of insulin signaling.
AB  - Insulin signaling involves the transient activation/inactivation of various
      proteins by a cycle of phosphorylation/dephosphorylation. This dynamic process is
      regulated by the action of protein kinases and protein phosphatases. One family
      of protein kinases that is important in insulin signaling is the mitogen
      activated protein (MAP) kinases, whose action is reversed by specific MAP kinase
      phosphatases (MKPs). Insulin stimulation of Hirc B cells overexpressing the human
      insulin receptor resulted in increased MKP-1 mRNA levels. MKP-1 mRNA increased in
      a dose-dependent manner to a maximum of 3- to 4-fold over basal levels within 30
      min, followed by a gradual return to basal. The mRNA induction did not require
      the continuous presence of insulin. The induction of MKP-1 protein synthesis
      followed MKP-1 mRNA induction; MKP-1 protein was maximally expressed after 120
      min of insulin stimulation. MKP-1 mRNA induction by insulin required insulin
      receptor tyrosine kinase activity, since overexpression of an altered insulin
      receptor with impaired intrinsic tyrosine kinase activity prevented mRNA
      induction. Forskolin, (Bu)2-cAMP, 8-bromo-cAMP, and 8-(4-chlorophenylthio)-cAMP
      increased the MKP-1 mRNA content moderately above basal. These agents also
      augmented the insulin-stimulated expression of MKP-1 mRNA. However, in some cases
      the increase in MKP-1 mRNA expression was less than additive. Nevertheless, these
      results indicate that multiple signaling motifs might regulate MKP-1 expression
      and suggest another mechanism for the attenuation of insulin-stimulated MAP
      kinase activity by cAMP. Overexpression of MKP-1 in Hirc B cells inhibited both
      insulin-stimulated MAP kinase activity and MAP kinase-dependent gene
      transcription. The results of these studies led us to conclude that insulin
      regulates MKP-1 and strongly suggest that MKP-1 acts as a negative regulator of
      insulin signaling.

PMID- 9280069
TI  - Inefficient secretion of human H27A-prolactin, a mutant that does not bind Zn2+.
AB  - Human PRL binds Zn2+, but the function of the binding is not known. We
      investigated the effect on PRL production in pituitary cells by obtaining clones
      of GH4C1 cells stably transfected with human H27A-PRL, a mutant that does not
      bind Zn2+. Unexpectedly, clones transfected with the mutant human PRL made little
      rat PRL. Untransfected GH4C1 cells made between 0.5 to 10 microg rat PRL/10(5)
      cells in 24 h. Clones transfected with vector alone (four of four), wild type
      human PRL (six of six), or with human K69A-PRL (two of two) made amounts of rat
      PRL in the same range. Clones transfected with human H27A-PRL (five of five) made
      0.003-0.1 microg rat PRL/10(5) cells in 24 h, and the production of rat PRL mRNA
      was reduced. Human H27A-PRL was not efficiently secreted; 20-40% newly
      synthesized H27A-PRL was degraded by 60 min, and there was usually a delay in
      release of newly synthesized H27A-PRL. Reduction of rat PRL production is not
      mediated through the PRL receptor, because no sequences for the receptor in GH4C1
      cells were detected by RT-PCR. Proteins involved in folding, such as BiP, were
      not specifically elevated in the H27A-PRL clones. In transient transfections, in
      which cells have not undergone selection, we found no evidence for disulfide
      bonded aggregates of the mutant protein. The results indicate that Zn2+ binding
      stabilizes PRL in the secretory pathway; the instablility of the mutant protein
      may trigger effects that suppress rat PRL production directly or that indirectly
      result in selection of clones with low rat PRL production.

PMID- 9280070
TI  - Phosphoinositide 3-kinase is required for insulin-induced but not for growth
      hormone- or hyperosmolarity-induced glucose uptake in 3T3-L1 adipocytes.
AB  - The(1) regulatory mechanism of glucose uptake in 3T3-L1 adipocytes was
      investigated with the use of recombinant adenovirus vectors encoding various
      dominant negative proteins. Infection with a virus encoding a mutant regulatory
      subunit of phosphoinositide (PI) 3-kinase that does not bind the 110-kDa
      catalytic subunit (delta p85) inhibited the insulin-induced increase in PI 3
      kinase activity co-precipitated by antibodies to phosphotyrosine and glucose
      uptake in a virus dose-dependent manner. Overexpression of a dominant negative
      RAS mutant in which Asp57 is replaced with tyrosine (RAS57Y) or of a dominant
      negative SOS mutant that lacks guanine nucleotide exchange activity (delta SOS)
      abolished the insulin-induced increase in mitogen-activated protein kinase
      activity, but had no effect on PI 3-kinase activity or glucose uptake. Although
      GH and hyperosmolarity attributable to 300 mM sorbitol each promoted glucose
      uptake and translocation of glucose transporter (GLUT)4 to an extent comparable
      to that of insulin, these stimuli triggered little or no association of PI 3
      kinase activity with tyrosine-phosphorylated proteins. Overexpression of delta
      p85 or treatment of cells with wortmannin, an inhibitor of PI 3-kinase activity,
      had no effect on glucose uptake or translocation of GLUT4 stimulated by GH or
      hyperosmolarity. Moreover, overexpression of delta SOS or RAC17N also did not
      affect the increase in glucose uptake induced by these stimuli. A
      serine/threonine kinase Akt, a constitutively active mutant of which was
      previously shown to stimulate glucose uptake, is activated by insulin, GH, and
      hyperosmolarity to approximately 4-fold, approximately 2.1-fold, and
      approximately 2.3-fold over basal level, respectively. These results suggest that
      insulin-induced but neither GH- or hyperosmolarity-induced glucose uptake is PI 3
      kinase-dependent, and neither RAS nor RAC is required for glucose uptake induced
      by these stimuli in 3T3-L1 adipocytes.

PMID- 9280071
TI  - Detection and classification of early squamous cell esophageal cancer.
AB  - The authors analyzed 230 cases of T1 cancer of the thoracic esophagus resected in
      our surgical department between 1985 and 1996. This study showed that mucosal
      cancer was superior to submucosal cancer with respect to the 5-year survival rate
      (84% vs 64%), the incidence of lymph node metastasis (2% vs 42%) and the
      incidence of vascular invasion (8% vs 79%); therefore, the true early cancer of
      the esophagus can be defined as mucosal cancer of the esophagus. As for
      endoscopic classification, 93% of the 0-IIb subtype lesion and 80% of the 0-IIc
      subtype were mucosal cancer. Endoscopic staining with Lugol's solution can
      produce more precise information in the diagnosis of such flat lesions. Important
      points in screening for the detection of mucosal cancer of the esophagus include:
      (i) esophagoscopy for patients with only slight esophageal symptoms; (ii) annual
      endoscopic examination for high-risk populations; and (iii) endoscopic staining
      with Lugol's solution for abnormal findings on conventional endoscopy.

PMID- 9280072
TI  - Extent of resection and lymphadenectomy in early squamous cell esophageal cancer.
AB  - To decide the extent of resection and lymphadenectomy in early esophageal cancer,
      accurate diagnosis at the preoperative stage is essential. Because in mucosal
      cancer lymph node metastasis is hardly ever seen, minimal invasive surgery, by
      endoscopic mucosal resection is indicated. On the other hand, for submucosal
      cancer lymph node metastasis the rate is as high as 26-45%, therefore, standard
      resection and systematic lymphadenectomy is indicated, corresponding to that for
      advanced cancer. In Japan the 5-year survival rate after resection is 98-100% for
      mucosal cancer and 67-90% for submucosal cancer.

PMID- 9280073
TI  - Prognosis of early squamous cell carcinoma of the esophagus after surgical
      therapy.
AB  - Between 1980 and 1995, 91 (13.7%) out of 666 patients were determined by
      pathologic staging to have a superficial squamous-cell esophageal carcinoma of
      the thoracic esophagus. The male to female ratio was 3.3:1, and the mean age 60
      years. Postoperative mortality was 4.3%. The median follow-up was 48 months
      (range 3-179). Survival was significantly decreased with increased depth of
      tumour invasion and presence of nodal metastases (P=0.03). Recurrent disease was
      prevalent in patients with submucosal tumours compared to those with mucosal
      tumours (P < 0.05). Only intra-epithelial and intramucosal carcinomas deserve the
      definition of 'early' tumours. Given the relative inaccuracy of current staging
      modalities and the low morbidity and mortality rates associated with surgical
      resection, surgery appears to be the mainstay of treatment of superficial
      squamous-cell esophageal cancer.

PMID- 9280074
TI  - Role of surveillance endoscopy, biopsy and biomarkers in early detection of
      Barrett's adenocarcinoma.

PMID- 9280075
TI  - Extent of resection and lymphadenectomy in early Barrett's cancer.
AB  - The recognition of Barrett's esophagus as a premalignant condition has led to
      aggressive endoscopic screening protocols aimed at detecting adenocarcinoma in
      this organ. This policy has resulted in an increasing number of patients who
      present with 'early Barrett's cancer'. In the existing literature, very little
      data address patients with these lesions and, therefore, no consistent definition
      of early Barrett's cancer currently exists. Additionally, the extent of resection
      and lymphadenectomy that should be performed is not known. We define early
      Barrett's cancer as clinical T1N0M0 adenocarcinoma. We perform en bloc
      esophagectomy with radical lymphadenectomy for these lesions because current data
      suggest that a more radical operation may improve survival in patients with
      esophageal cancer. It is also the only way to stage adequately the tumour and is
      associated with morbidity and mortality rates comparable to less radical,
      'standard' resections in experienced hands. Barrett's esophagus is associated
      with invasive adenocarcinoma in 40% of patients who undergo esophagectomy for the
      preoperative diagnosis of high-grade dysplasia. The existing literature suggests
      these lesions may represent the earliest subset of Barrett's cancer and that a
      standard, less radical resection may suffice for these patients.

PMID- 9280076
TI  - Prognostic differences between early squamous-cell and adenocarcinoma of the
      esophagus.

PMID- 9280077
TI  - Surveillance of Barrett's esophagus: a need for guidelines?
AB  - Barrett's esophagus carries a 10-15% lifetime risk of malignant change, and
      dysplasia may be an early indication of such transformation. Endoscopic
      surveillance is widely practised but guidelines have not been established. A
      questionnaire regarding surveillance protocols was sent to all consultants in the
      Trent Region performing endoscopy (n = 79), of whom 58 (73%) replied.
      Surveillance is performed by 52 clinicians (90%), but the interval varies between
      1 and 3 years. Routine biopsies are only taken by 38 (65%), of which 74% are
      taken randomly. Detection of low-grade dysplasia would lead 32 (62%) to reduce
      the surveillance interval. For high-grade dysplasia, a reduced surveillance
      interval or surgery is advocated by 36 (69%) and 13 (25%), respectively. Most
      clinicians (74%) discontinue surveillance at age 70 or 75. Surveillance of
      Barrett's esophagus is variable, especially in the presence of dysplasia. No
      surveillance guidelines are available, but most respondents (79%) believe these
      would help.

PMID- 9280078
TI  - Prevalence, management and outcome of early adenocarcinoma (pT1) of the esophago
      gastric junction. Comparison between early cancer in Barrett's esophagus (type I)
      and early cancer of the cardia (type II).
AB  - The study compares, in true adenocarcinoma of the cardia and in adenocarcinoma in
      Barrett's esophagus, the prevalence of early cancers and their outcome in those
      patients suitable for resection surgery. From 1980 to 1993, 26 of 350 (7.4%)
      resected adenocarcinomas of the esophago-gastric junction were pathologically
      staged as early cancer or pT1. The prevalence of early cancer was 3.7% (11/294)
      for true cancer of the cardia and 27% (15/56) for cancer in Barrett's esophagus
      (P < 0.001). Ten of the 15 latter cancers were diagnosed during endoscopic
      surveillance for benign Barrett's esophagus. Among early cancers, there were four
      mucosal and 22 submucosal tumours; of the latter, eight had lymph node metastasis
      and seven neoplastic permeation of lympho-hematic vessels. The most frequently
      used surgical procedure was esophago-gastric resection and gastric pull-up.
      Postoperative morbidity was 15.4%, and hospital mortality 3.8%. Excluding
      postoperative deaths, the overall 5-year survival rate was 79% for early cancer
      of the cardia and 83% for early cancer in Barrett's esophagus (log rank test =
      0.0214, P = 0.88). Overall, the survival rate was 100% in the absence of lymph
      node metastasis and 43% in the presence of node metastasis (log rank test =
      15.811, P = 0.0001). Only one of five patients with both node metastasis and
      vessel infiltration survived longer than 5 years. In conclusion, the prevalence
      of early cancer was significantly greater for cancer in Barrett's esophagus than
      for true cancer of the cardia. Prognosis of the two types of tumour after
      resection surgery was the same and depended on lymph node status and neoplastic
      permeation of lympho-hematic vessels.

PMID- 9280079
TI  - Helicobacter pylori colonization of Barrett's esophagus and its progression to
      cancer.
AB  - Helicobacter pylori (HP) plays a crucial role in gastric carcinogenesis. Few
      studies have looked at the relationship between HP and Barrett's
      esophagus/cancer. To further investigate this, a study comparing the prevalence
      of HP and increasing grades of dysplasia was undertaken. Biopsies from 19
      malignant and 94 benign cases of Barrett's esophagus were analysed histologically
      for the presence of HP. 34% of non-dysplastic Barrett's epithelium was colonized
      with HP compared with only 17% of dysplastic/malignant cases (P = 0.04). No
      relationship was found between HP status and: (i) length of Barrett's esophagus;
      (ii) the presence of ulcers or strictures; and (iii) previous anti-reflux
      surgery. HP colonization of Barrett's esophagus is not uncommon. We found that HP
      has a negative correlation with increasing dysplasia which is analogous to
      gastric carcinogenesis. This finding should be investigated in prospective
      studies to elucidate its role in Barrett's adenocarcinoma.

PMID- 9280080
TI  - Early diagnosis of mucosal squamous cell carcinoma of the esophagus: including
      two interesting cases of superficial spreading-type and multicentric-type
      squamous cell carcinomas.
AB  - We reviewed 10 patients with esophageal mucosal carcinoma in order to improve the
      early diagnosis of the disease. Histologically seven of the 14 lesions were
      carcinomas in situ (epithelial cancer), and the other seven lesions were
      carcinomas confined to the mucosa other than epithelial cancer (muscularis
      mucosae cancer), all 14 lesions were squamous cell carcinomas (SCC). One of these
      seven mucosal SCC, which demonstrated an extensive spreading-type SCC in which
      the size of the SCC was 7 cm long while extending entirely around the esophageal
      lumen in circumferential spread, is described in detail, and multiple epithelial
      cancers existed separately in one case. Eleven lesions diagnosed before operation
      showed abnormal findings on conventional endoscopy regardless of the size and
      depth of transmural invasion. An additional lesion was visible with dye endoscopy
      as an unstained area, but it was not visible with radiography or conventional
      endoscopy. Dye endoscopy using Lugol solution is very important because it allows
      detection and evaluation of the extent of esophageal mucosal cancer.

PMID- 9280081
TI  - Flow cytometry in squamous cell esophageal cancer and precancerous lesions.
AB  - Flow cytometry has also been used to study the nuclear DNA content (ploidy) and
      cell cycle kinetics of esophageal cancers. Studies of limited numbers of patients
      with Barrett's esophagus undergoing endoscopic surveillance suggested that
      aneuploidy may be a useful marker to identify subsets of patients at increased
      risk for malignancy. Few studies to date have evaluated premalignant tissues
      associated with the development of squamous-cell cancer of the esophagus. The
      present retrospective study comprises 80 surgical specimens of squamous-cell
      carcinoma of the esophagus from a high-incidence region of Thailand. All patients
      had surgery at the Department of Surgery, Prince of Songkla University, between
      March 1983 and December 1993. Sets of serial sections were cut every 0.5 cm
      starting from the proximal margin and down to the distal margin, and
      histopathology was confirmed to flow cytometric parameters (DNA content, S-phase
      fraction). Aneuploidy was found in 84% of squamous-cell carcinoma, 22.2% of
      carcinoma in situ, 28.6% of severe dysplasia, 11.0% of moderate dysplasia and 0%
      of mild dysplasia and normal esophageal mucosa specimens. The percentage was
      higher according to the level of severity or dysplasia. S-phase fraction was
      found to be 21.0 +/- 0.9% in squamous-cell carcinoma, 20.3 +/- 10.3% of carcinoma
      in situ, 20.9 +/- 5.3% of severe dysplasia, 12.9 +/- 9.7% of moderate dysplasia
      7.6 +/- 0.8% of mild dysplasia and 8.9 +/- 3.2% of normal tissue. Similarly, the
      percentage of S-phase fraction tends to be higher according to the level of
      severity or dysplasia. These findings demonstrate that the aneuploidy and
      percentage of S-phase fraction tend to correlate with progression of esophageal
      premalignant tissues to invasive carcinoma. These measures may be clinically
      useful to identify patients at increased risk for esophageal malignancy.

PMID- 9280083
TI  - Ischemic conditioning of the stomach may reduce the incidence of esophagogastric
      anastomotic leaks complicating esophagectomy: a hypothesis.
AB  - Esophagogastric anastomotic leaks are a major cause of morbidity and mortality
      after esophagectomy. Occult ischemia of the mobilized and partially
      devascularized gastric fundus is an important cause of esophagogastric leaks. The
      author hypothesizes that the vascularity of the gastric fundus can be improved,
      and anastomotic leaks reduced, by a process of ischemic conditioning (delay
      phenomenon). Laparoscopic partial gastric devascularization could be performed 2
      3 weeks before esophagectomy. The gastric fundus would have time to re-establish
      an abundant blood supply before being mobilized and anastomosed to the esophagus.
      Since laparoscopic partial devascularization could be done at the time of
      laparoscopic cancer staging, gastric ischemic conditioning would not necessarily
      add cost or morbidity to the overall treatment of esophageal cancer. Laboratory
      and clinical evidence are presented to support this hypothesis.

PMID- 9280082
TI  - Patient perception and localization of dysphagia -- barium study correlation.
AB  - We assessed the accuracy of patient localization of the site of dysphagia and its
      implications for radiological practice during the barium swallow examination.
      Several current texts dispute the value of such information. Fifty-two
      consecutive patients with dysphagia were asked to localize the site of discomfort
      on the skin surface. The ability of each patient to do so precisely or vaguely
      was noted. A detailed barium examination of the pharynx, esophagus and stomach
      was performed. Results suggested that patients who had symptoms more cranial than
      the sternal notch were highly accurate at localizing disease. Localization became
      less precise as symptoms moved caudally towards the epigastrium. Lateralization
      of symptoms was highly accurate in determining the site of pathology. In
      conclusion, we feel that in certain circumstances the barium examination can be
      usefully tailored to accelerate examination times, thus reducing radiation
      exposure and cost whilst improving diagnostic accuracy.

PMID- 9280084
TI  - Pseudoachalasia: a report of two cases with comments on possible causes and
      diagnosis.
AB  - Pseudoachalasia is a rare entity with symptoms and radiographic and esophageal
      manometric findings that may mimic primary achalasia. Two such cases are
      presented, one of which was associated with gastric carcinoma and the other with
      carcinoma of the lung.

PMID- 9280085
TI  - Intramural esophageal hematoma after cardioversion.
AB  - Intramural esophageal hematoma is a very rare condition. We report a case of a 40
      year-old male, presenting with retrosternal pain and dysphagia. On the day before
      admission tarry stool and minimal vomiting of old blood was noticed. Diagnostic
      procedures showed an intramural esophageal hematoma, which had developed 2 weeks
      and 3 days after cardioversion and anticoagulation therapy. Etiology,
      differential diagnosis, the diagnostic approach and a brief review of the
      literature are discussed.

PMID- 9280087
TI  - The new neonatology: CAC.

PMID- 9280086
TI  - Resection of the paraesophageal hernia sac.
AB  - A simple technique for resection and closure of the paraesophageal hernia sac is
      described.

PMID- 9280088
TI  - Effects of exogenous surfactant on neonates supported by extracorporeal membrane
      oxygenation.
AB  - OBJECTIVE: The purpose of this study was to evaluate the impact of exogenous
      surfactant on the duration of extracorporeal membrane oxygenation needed to
      support neonates. STUDY DESIGN: Retrospective case review. RESULTS: The duration
      of extracorporeal membrane oxygenation decreased from 112 +/- 43.3 hours to 76 +/
      17.9 hours. There was no difference in duration of mechanical ventilation,
      duration of supplemental oxygen, incidence of chronic lung disease, or length of
      hospital stay. CONCLUSION: Surfactant administered soon after initiation of
      extracorporeal membrane oxygenation results in a significant reduction in the
      duration of extracorporeal support for neonates.

PMID- 9280089
TI  - Maternal and neonatal outcome of pregnancies complicated with maternal HELLP
      syndrome.
AB  - Preeclampsia complicated by the HELLP syndrome is associated with poor maternal
      outcome; there is scant information on neonatal outcome. OBJECTIVE: To evaluate
      the outcome of infants born to mothers with HELLP syndrome. STUDY DESIGN: Chart
      review comparing perinatal variables and the clinical course of 23 infants born
      to mothers whose pregnancy was complicated with HELLP syndrome (H) with 23
      infants of mothers with uncomplicated preeclampsia (P). RESULTS: Infants in the H
      group, when compared with those in the P group, had a higher incidence of low
      Apgar scores (52% vs 18%, p < 0.01), lower admission systolic blood pressure (45
      +/- 7 vs 32 +/- 11, p < 0.01), and more frequent need for assisted ventilation
      (61% vs 30%, p < 0.05). There were no differences between the two groups of
      infants in hematocrit, leukocyte and platelet count, or duration of ventilation
      and hospitalization. CONCLUSIONS: These findings suggest that infants born to
      preeclamptic mothers who develop HELLP syndrome have an increased need for
      resuscitation at delivery and a higher incidence of postnatal cardiopulmonary
      instability. Thus mothers with HELLP syndrome should be identified promptly and
      delivered in level II or III centers with appropriate facilities for management
      of these newborn infants at risk for perinatal asphyxia and a potential for long
      term neurologic sequelae.

PMID- 9280090
TI  - Maternal and paternal risk factors and adverse neonatal outcomes among Hispanic
      subgroups in Illinois (1989 through 1993).
AB  - OBJECTIVES: The study purposes were to examine maternal and paternal high-risk
      factors and note associated differences in birth outcomes among Hispanic
      subgroups compared with white and black populations in Illinois. STUDY DESIGN:
      Computerized birth certificate data of 131,768 Hispanic singleton neonates (14.1%
      of all Illinois births from 1989 through 1993) were compared among five Hispanic
      subgroups. Matched infant birth-death computerized files were obtained for
      neonatal and postneonatal mortality (1989 through 1992 birth cohorts) and
      separate fetal mortality tables were also examined. RESULTS: Whereas Puerto Rican
      mothers had higher prevalence rates for various maternal risk factors and higher
      infant morbidity rates among the five Hispanic groups, infants of Cuban mothers
      had significantly higher fetal and infant mortality rates. CONCLUSIONS: Our study
      identified substantial differences during the prenatal period and in birth
      outcomes among the five Hispanic subgroups. Those differences may help us develop
      innovative targeted interventions.

PMID- 9280091
TI  - Optimizing the approach to anemia in the preterm infant: is there a role for
      erythropoietin therapy?
AB  - OBJECTIVE: To define a subset of very low birth weight (VLBW) infants who might
      benefit from recombinant human erythropoietin (r-HuEPO) treatment. STUDY DESIGN:
      We reviewed the records for all VLBW (birth weight (BW) < or = 1500 gm) infants
      who were admitted to our nursery within the first 3 days of life between January
      1991 and December 1994 and discharged alive. RESULTS: These infants received an
      average of 2.02 transfusions, far fewer than the 7 to 11 previously reported for
      VLBW infants. Infants with a BW of 1251 to 1500 gm received very few
      transfusions. More than three quarters of transfused infants received a
      transfusion in the first 2 weeks of life before r-HuEPO would be expected to be
      effective. Assigning units to individual infants and holding the units for 14
      days, a practice adopted in our blood bank in 1993, resulted in a 44% decrease in
      donor exposures in infants receiving more than one transfusion. Holding assigned
      units for 30 days, a practice our blood bank has now adopted, should result in
      56% of all transfused infants having a single donor exposure and 89% having one
      or two donor exposures. Cost-benefit analysis only supports routine use of r
      HuEPO in infants weighing less than 750 gm. CONCLUSION: VLBW infants receive far
      fewer transfusions than the number previously reported. Assigning units to
      individual patients and holding those units for 30 days, together with efforts to
      minimize the need for transfusions make routine use of r-HuEPO unnecessary.

PMID- 9280092
TI  - Parental factors influencing patterns of prenatal care utilization.
AB  - OBJECTIVES: The objectives of this study are to examine the influence of paternal
      and maternal education and marital status on the initiation and adequate use of
      prenatal care services. METHODS: Data were obtained from the 1990-1991 Minnesota
      Live Birth file. Single live births to white resident mothers who were 21 years
      of age or older were selected for investigation. After these selections 102,798
      cases were analyzed. RESULTS: Logistic regression was used to examine the
      association of parental characteristics on the following three measures of poor
      prenatal care use: (1) receiving no prenatal care; (2) initiating care later than
      the first trimester; and (3) given a first trimester start of care, receiving
      less than the recommended number of prenatal care visits. Within each maternal
      education stratum, an increased risk of delayed initiation and less efficient use
      of prenatal care were observed for lower paternal educational attainment.
      Unmarried women, regardless of educational level, exhibited more than a tenfold
      risk of receiving no prenatal care, and unmarried women of low educational
      attainment exhibited the highest risk of delayed care. CONCLUSIONS: A persistent
      positive effect of increasing paternal education on the level of adequacy of
      prenatal care utilization within all maternal marital status and educational
      attainment groups poses further challenges to our understanding of the factors
      that influence prenatal care use.

PMID- 9280093
TI  - Risk factors for febrile, presumed viral illness in the first ten weeks of life.
AB  - OBJECTIVE: We attempted to identify demographic and environmental factors
      associated with development of febrile, presumed viral illness in infants < or =
      10 weeks old. STUDY DESIGN: The study was conducted in a large, urban pediatric
      hospital and outpatient clinics. Infants < or = 10 weeks old admitted to the
      hospital for a febrile illness but discharged with a presumed viral illness as
      the cause of the fever (n = 106) were compared with afebrile infants who came for
      clinic appointments (n = 87). Thirty-three infants found to have a bacterial
      source of illness were dropped from analysis. RESULTS: Recent exposure to an
      acute respiratory illness in the home (p < 0.0001), a previous visit to the
      doctor that was unrelated to the hospitalization (p < 0.002), having a sibling in
      school or day care (p < 0.007), and exposure to two or more smokers in the home
      (p < 0.011) were associated with development of a presumed viral illness with
      fever. CONCLUSION: Families with young infants should be counseled to keep their
      babies away from cigarette smoke or individuals with colds or presumed viral
      illnesses.

PMID- 9280094
TI  - Nonpathologic ventriculomegaly in the premature intrauterine growth retarded
      infant.
AB  - OBJECTIVE: To determine any neurosonographic differences between premature
      intrauterine growth retarded (IUGR) neonates and premature appropriate for
      gestational age (AGA) infants. STUDY DESIGN: We retrospectively reviewed the head
      sonograms of 36 premature IUGR infants and 32 premature AGA matched controls.
      RESULTS: Seven of the 36 (19%) IUGR infant head sonograms revealed mild
      ventriculomegaly with no evidence of hemorrhage or ischemia. Only one of the 32
      control scans (3%) had similar findings. Mild ventriculomegaly in the IUGR infant
      versus the AGA control neonate was statistically significant (p value of 0.05).
      Follow-up head sonograms (4 to 12 weeks after the initial head sonogram) revealed
      resolution of the mild ventriculomegaly in five of the seven IUGR infants.
      Clinically, all of the IUGR infants with mild ventriculomegaly were asymptomatic
      during their stay in the nursery and in clinical follow-up ranging from 3 to 5
      years. CONCLUSION: Mild ventriculomegaly on the head sonograms of asymptomatic
      premature IUGR infants (with no associated hemorrhage or ischemic change) should
      be recognized as a transient, nonpathologic finding.

PMID- 9280095
TI  - Age greater than thirty-four years is an independent pregnancy risk factor in
      nulliparous women.
AB  - OBJECTIVE: To compare quantitative pregnancy risk of nulliparous women 35 years
      and older with nulliparous women 25 to 29 years old. STUDY DESIGN: Maternal
      records for first births at three suburban hospitals from July 1, 1986, to June
      30, 1990, were studied, risk-assessed retrospectively according to a group
      specific risk-scoring system, and compared statistically according to age and
      quantitative pregnancy risk. RESULTS: The older women were more likely to be high
      risk (score > or = 10) prepregnancy (odds ratio [OR] 2.9, 95% confidence interval
      [CI] 1.9 to 4.5), antepartum (OR 1.6, 95% CI 1.3 to 2.0), intrapartum (OR 2.2,
      95% CI 1.8 to 2.6), and cumulatively (OR 2.6, 95% CI 2.2 to 3.2) when compared
      with younger women. They were also more likely to be very high risk (score > or =
      20) antepartum (OR 1.8, 95% CI 1.1 to 2.9), intrapartum (OR 2.1, 95% CI 1.5 to
      2.8), and cumulatively (OR 2.5, 95% CI 2.0 to 3.2). Risk increased progressively
      through pregnancy, revealing the intrapartum period as the time interval of
      maximum risk. Based on cumulative risk scoring, 64.9% of the older women were at
      least high risk, compared with 41.3% of the younger women (OR 2.6, 95% CI 2.2 to
      3.2). CONCLUSION: Nulliparous women 35 years and older from a predominantly
      middle-class, white population had a significantly higher quantifiable pregnancy
      risk than a similar group of women age 25 to 29, suggesting that age greater than
      34 years is an independent pregnancy risk factor.

PMID- 9280096
TI  - Selective second-trimester termination of an abnormal fetus in twin pregnancies.
AB  - The probability of detecting a chromosomal or structural abnormality in one fetus
      of a dizygotic twin gestation is about twice that of the risk for a singleton.
      During the period January 1992 to October 1994 we performed selective termination
      of the abnormal fetus in 14 bichorionic twin gestations. Indications for
      selective termination were 10 structural abnormalities and 4 chromosomal
      abnormalities. The procedure was done at 14, 16, and between 20 and 25 weeks in
      1, 2, and 11 cases, respectively. We had no pregnancy losses before 24 weeks'
      gestation. The mean gestational age at delivery was 34.2 +/- 3.9 (SD) weeks. In
      one case, severe abruptio placentae occurred and the neonate died. Thirteen
      neonates are alive and well. In five cases in which the procedure was done after
      21 weeks' gestation, no decrease in the amount of amniotic fluid in the sac of
      the terminated fetus was observed. Our experience supports the general conclusion
      that selective termination for bichorionic abnormal twins is safe and effective.

PMID- 9280097
TI  - Urinary tract infection in premature infants: the role of imaging studies and
      prophylactic therapy.
AB  - BACKGROUND: The prevalence of urinary tract infection (UTI) in premature infants
      ranges from 4% to 25%. It is surprising, however, that scant information exists
      regarding management of UTI in premature infants, particularly the need for
      radiologic evaluation of the urinary tract and the use of preventive antibiotic
      therapy after the first episode of UTI occurs. The aim of this study was to
      answer these questions. PATIENTS AND METHODS: Twenty-seven (8%) premature infants
      (< 1750 gm birth weight) born during the period from 1990 through 1993 had UTI.
      Eleven of them were of extreme low birth weight (ELBW) (birth weight < 1000 gm).
      Ultrasound examination of the urinary tract was performed in all premature
      infants 7 days after a diagnosis of UTI was made and was repeated 1 month later,
      if disease was detected. Voiding cystography was performed in 21 premature
      infants (8 with ELBW) 6 to 8 weeks after a diagnosis of UTI was made. RESULTS:
      The mean birth weight of premature infants with UTI was 1112 +/- 294 gm. The
      prevalence of UTI was significantly higher (p < 0.01) in infants with ELBW (13%)
      compared with that in premature infants with birth weight >1000 gm (6%). The
      male/female ratio in all premature infants was 2.9:1 and was significantly higher
      in infants with ELBW (10:1; p < 0.01). Organisms involved were Klebsiella (59%),
      Candida albicans (15%), Escherichia coli (15%), and Enterobacter (11%). Only
      premature infants with ELBW had Candida UTI. Five premature infants (four with
      ELBW) had mild transient hydronephronis, and one had persistent hydronephrosis
      and hydroureter. Voiding cystography showed that three premature infants had
      vesicoureteral reflux and that one had a bladder diverticulum. All premature
      infants with pathologic voiding cystography had birth weight >1000 gm and had
      normal ultrasound examination. CONCLUSIONS: Premature infants with birth weight
      1000 to 1750 gm should be given preventive antibiotic therapy at least until
      imaging evaluation (ultrasonography and voiding cystography) is complete.
      Premature infants with ELBW are more susceptible to fungal infection and do not
      seem to have underlying urinary tract abnormalities. Prophylactic therapy and
      voiding cystography may be unwarranted in this population subset.

PMID- 9280098
TI  - Increasing use of antenatal corticosteroid therapy between 1990 and 1993 in
      Vermont Oxford Network.
AB  - OBJECTIVE: The purpose of this study was to determine whether the frequency of
      antenatal corticosteroid treatment changed between 1990 and 1993 and to identify
      patient characteristics associated with the use of this treatment. STUDY DESIGN:
      A total of 17,335 infants born in the years 1990 to 1993 with birth weights of
      1500 gm or less and gestational ages of 24 to 34 weeks who were cared for at one
      of the 94 institutions participating in the Vermont Oxford Network were included
      in the study. Ninety-one infants were excluded from analysis because of missing
      data, resulting in a final sample of 17,244 infants. RESULTS: The percentage of
      infants whose mothers received antenatal corticosteroid treatment increased
      steadily during the 4-year study period (19.3% in 1990, 24.8% in 1991, 28.6% in
      1992, and 34.1% in 1993; p < 0.001 by chi square test for trend in proportions).
      The results of a logistic regression analysis indicated that increasing year of
      birth, inborn location of birth, prenatal care, and multiple birth were
      associated with an increased use of antenatal corticosteroid treatment; black
      race and small size for gestational age were associated with decreased use of the
      treatment. In 1993, the median percentage of infants at an individual institution
      whose mothers received antenatal corticosteroid treatment was 25%; 10% of
      institutions had percentages less than 7% and 10% had percentages higher than
      60%. CONCLUSION: Although the use of antenatal corticosteroid treatment increased
      steadily during the study period, this treatment was still used infrequently at
      many institutions in 1993. Considerable improvements in outcomes for preterm
      infants can be achieved if the recommendations of the National Institutes of
      Health Consensus Development Panel regarding more widespread use of antenatal
      corticosteroid treatment are adopted by health professionals who provide medical
      care to pregnant women.

PMID- 9280099
TI  - Induced early delivery of a fetus with hypoplastic left heart: a moral choice
      when neither surgery nor abortion is an acceptable option.

PMID- 9280100
TI  - Behcet's syndrome associated with intrauterine growth restriction: a case report
      and review of the literature.
AB  - BACKGROUND: Behcet's syndrome is an immune-mediated connective tissue disorder,
      and its primary manifestations are oral and genital ulcerations. To our knowledge
      no cases of adverse fetal outcome have been reported in pregnancies complicated
      by this disease. CASE: A 27-year-old primigravid woman with a diagnosis of
      Behcet's disease came to our institution during the first trimester. Her
      pregnancy was complicated by several exacerbations of her disease including
      vaginal and oral ulcerations and abdominal pain. She was treated with steroids
      throughout her pregnancy. She had ruptured membranes and evidence of fetal
      distress at 361/2 weeks and subsequently delivered a severely growth-restricted
      fetus (< 3rd percentile). CONCLUSION: Pregnancies complicated by Behcet's disease
      should be monitored closely for evidence of intrauterine growth restriction and
      fetal compromise, as are pregnancies complicated by similar connective tissue
      disorders.

PMID- 9280101
TI  - Osteomyelitis pubis occurring after spontaneous vaginal delivery: a case
      presentation.
AB  - BACKGROUND: Osteomyelitis pubis is an uncommon disorder. The clinical
      presentation is similar to that of osteitis pubis, which is a self-limiting
      condition. However, osteomyelitis pubis necessitates intensive intravenous
      antibiotic therapy and, frequently, surgery to effect a cure. CASE: A 33-year-old
      gravida II para 1001, Filipina vaginally delivered a 3802 gm baby on April 5,
      1994. The delivery was complicated by shoulder dystocia. Her postpartum course
      was complicated by an abscessed tooth and pubic pain that was exacerbated by
      ambulation. On the twentieth postpartum day, she came to the emergency department
      with massive cellulitis of the mons veneris and labia majora. The results of an x
      ray examination and bone scan were consistent with osteomyelitis of the pubis.
      The patient did not respond to multiple intravenous antibiotics, and surgical
      debridement was required. CONCLUSIONS: A diagnosis of osteomyelitis pubis should
      be considered for any patient who experiences pubic pain that is exacerbated by
      walking. Proper therapy consists of intravenous antibiotics and surgical
      debridement, as necessary, in patients who do not respond to antibiotics.

PMID- 9280102
TI  - Special imaging casebook. Unilateral renal cystic disease in a horseshoe kidney.

PMID- 9280103
TI  - Placental casebook.

PMID- 9280105
TI  - Managing unexplained anterior knee pain.

PMID- 9280104
TI  - Technical Bulletin 163: A light at the end of the tunnel.

PMID- 9280106
TI  - Scarring of the anterior cruciate ligament to the posterior cruciate ligament
      does not decrease anterior translation.
AB  - Frequently, a patient undergoing anterior cruciate ligament (ACL) reconstruction
      4 to 6 weeks following the acute injury will be noted to have decreased anterior
      translation during a Lachman and anterior drawer testing at the time of surgery
      compared with their examination at the time of their acute injury. Orthopedic
      surgeons frequently attribute this decreased anterior translation to scarring of
      the ACL to the posterior cruciate ligament (PCL). We undertook a cadaver study to
      evaluate this. Four cadaveric lower extremity specimens underwent a midline
      posterior approach to the knee followed by arthrotomy. The ACL then was cut from
      its origin on the lateral femoral condyle. Following its release, the ACL was
      sutured tightly to the PCL. Prior to dissection, the specimens underwent baseline
      KT-1000 knee arthrometer testing. Following the arthrotomy but prior to ACL
      release, the KT-1000 test was repeated. KT-1000 testing then was performed after
      ACL release and repeated after suturing the ACL to the PCL. The results revealed
      no change in KT-1000 testing following arthrotomy. Anterior translation increased
      an average of 5 mm following release of the ACL and after suturing to the PCL. No
      specimen showed a significant decrease in anterior translation following suturing
      of the ACL to the PCL. These results indicate that while decreased anterior
      translation from the time of injury to the time of reconstruction may occur, this
      cannot be explained based on scarring of the ACL stump to the PCL.

PMID- 9280107
TI  - Retropatellar contact stress in simulated patella infera.
AB  - Six fresh-frozen cadaver knee joints were used to study changes in retropatellar
      contact mechanics accompanying patella infera. The knees were tested on a
      servohydraulic testing machine under conditions simulating stair descent at 10
      degrees, 30 degrees, 60 degrees, and 90 degrees of knee flexion. A slotted
      metallic block mechanism embedded in the region of the tibial tubercle allowed
      selective distal offset of the patellar tendon insertion so as to model
      conditions of 0, 6, 13, 19, and 25 mm of patella infera. Patellofemoral and
      quadriceps tendofemoral contact areas and contact stresses were recorded using
      Pressensor contact film and quantitated using digital image analysis. Patella
      infera significantly altered retropatellar contact mechanics. Contact areas
      migrated proximally on the patella and decreased in size with progressive
      severity of patella infera. However, the peak and spatial mean retropatellar
      contact stresses were not elevated correspondingly. Apparently, quadriceps
      tendofemoral contact was initiated at progressively lower angles of knee flexion
      as the patella infera progressed. Under conditions of extreme infera at high
      flexion angles, the magnitude of tendofemoral contact force approached that of
      retropatellar contact force. These data indicate that in patella infera,
      patellofemoral contact stresses are not elevated appreciably. Therefore, the
      disabling symptoms associated with patella infera may be due to factors other
      than local mechanical overload.

PMID- 9280108
TI  - Tensile stress of the lateral patellofemoral ligament during knee motion.
AB  - Abnormal patellar retinacular tension has been considered to result in patellar
      lateral subluxation/dislocation. In this study, an in vitro experimental model
      was developed to determine the tensile stress of the lateral patellofemoral
      ligament, the thickest portion of the retinaculum, under loading conditions
      simulating two knee motion patterns: passive knee motion and unweighted active
      knee extension. The results indicate that the tensile stress increased
      significantly before 30 degrees of knee flexion, which strongly supports the
      clinical findings that patellar subluxation/dislocation occurs at approximately
      20 degrees to 30 degrees knee flexion angles.

PMID- 9280109
TI  - Nonoperative treatment of widely displaced patella fractures.
AB  - Eighteen patients with displaced patellar fractures were treated nonoperatively.
      All of the fractures were displaced by at least 1 cm. Ambulation and knee flexion
      were encouraged as soon as pain permitted. Twelve of the patients were limited in
      their activities by medical illnesses. Six of these patients died, and the
      remaining patients underwent follow-up for 2 years. No patient had severe pain,
      and only three had acquired significant limitations in their activities from
      their fractures. Nine patients had either minimal or moderate activity
      restrictions. There were no complications from treatment. Nonoperative treatment
      is a reasonable option for displaced fractures of the patella, particularly in
      patients whose activities are limited by chronic illness. Better results,
      however, are possible with operative treatment.

PMID- 9280110
TI  - The posterior cruciate ligament: a review.
AB  - The posterior cruciate ligament (PCL) has acquired the attention given to the
      anterior cruciate ligament (ACL) 15 years ago. Although parallels can be drawn
      between the ACL and the PCL in general, PCL deficiency is generally more complex
      in its effect, evaluation, documentation, and treatment. While there has been a
      constant upgrading of the operative techniques, grafting tissue, and material, it
      is the correlation of anatomy and function that still lag behind. Conservative
      treatment, therefore, is the safe approach for a while but is not without limited
      function in many cases, leading to a decrease in activity level or preventing the
      patient from working. This article reviews PCL deficiency and presents our
      approach to this ligamentous deficiency.

PMID- 9280111
TI  - Occult localized osteonecrosis of the patella.

PMID- 9280113
TI  - Anterior knee pain in the adolescent: an anatomical approach to etiology.

PMID- 9280112
TI  - Sporotrichal arthritis of the knee.

PMID- 9280114
TI  - Office evaluation of patients with anterior knee pain.

PMID- 9280115
TI  - The management of anterior knee pain in the adolescent.

PMID- 9280116
TI  - Hypersegmented megakaryocytes and megakaryocytes with multiple separate nuclei in
      dogs treated with PNU-100592, an oxazolidinone antibiotic.
AB  - Megakaryocytes in normal dogs have a variety of nuclear forms. The most common
      variations are a single large multilobed nucleus or a segmented nucleus
      consisting of irregular nuclear lobes joined by strands of chromatin. Exaggerated
      segmentation (hypersegmentation) of the nucleus occurs in a small number of
      megakaryocytes. Megakaryocytes with multiple separate nuclei are infrequently
      observed. In a 1-mo toxicology study in young adult beagle dogs with PNU-100592,
      a new oxazolidinone antibacterial agent, a large increase in the number of
      megakaryocytes with hypersegmented nuclei and multiple separate nuclei was
      observed. The group mean platelet count was slightly decreased for most PNU
      100592-treated groups. Siderocytes were observed on peripheral blood smears, and
      ring sideroblasts were present on bone marrow smears. Minimal to mild toxicologic
      lesions were observed in the large intestine, rectum, kidneys, liver, and testes,
      primarily in the high-dose group. PNU-100592 may be useful in the study of the
      regulation of endomitosis during megakaryocytopoiesis in the dog.

PMID- 9280117
TI  - Toxicity of subacute intravenous manganese chloride administration in beagle
      dogs.
AB  - Manganese (Mn), a naturally occurring essential trace element, is currently being
      used as a metal complex for pharmaceutical and magnetic resonance imaging agents.
      Despite its popularity in these practices, minimal attention has focused on
      possible toxicity of released free Mn ions, which could occur if these agents
      decomplexed. There is especially limited information available regarding acute
      toxicity of Mn in dogs. In this study, we performed an in-depth evaluation of
      acute toxicologic potential of manganese chloride (MnCl2) when administered as a
      4-hr/day intravenous infusion to male beagle dogs. The dose of MnCl2 used (16
      mg/kg/day) was equivalent to approximately 3-5 times the daily dose of Mn
      typically administered in some of the Mn-complexed agents. All routine
      toxicologic endpoints were evaluated, including cardiovascular parameters. This
      dosing regimen resulted in the death or moribund sacrifice of all the animals
      within 4 days of initiation of treatment. Clinical evidence of toxicity included
      loss of appetite, reduction in blood pressure with reflex tachycardia, and a
      marked increase in liver enzymes, beginning with the first dose and increasing in
      severity with successive doses. Gross and histopathologic evaluations confirmed
      severe hepatotoxicity, which was characterized by massive hepatocellular
      necrosis, periportal hemorrhages, and mild biliary epithelial hyperplasia. These
      results indicate that acute treatment of beagle dogs with MnCl2 causes severe
      hepatotoxicity and hypotension with reflex tachycardia and suggest that dogs are
      very sensitive to toxic effects of Mn.

PMID- 9280118
TI  - Single-organism model of host defense against infection: a novel
      immunotoxicologic approach to evaluate immunomodulatory drugs.
AB  - The immunotoxicologic effects of drugs on host defense have been studied widely
      using various animal models of infection. Here we describe a new approach to
      testing host defense by using a single organism (Candida albicans) in CBA/J mice.
      The model is configured to test 3 effector systems via different routes of
      inoculation to stimulate different effector arms of the immune response.
      Nonspecific immunity was evaluated by C. albicans colony-forming unit (CFU) count
      from the spleen at 2 hr (uptake) and > or = 22 hr (clearance) following
      intravenous inoculation. Cell-mediated immunity was assessed by CFU count from an
      intramuscular injection site 6 days postinoculation. Humoral immunity was
      assessed by anti-Candida antibody titer, following multiple subcutaneous
      immunizations with C. albicans. Finally, overall immunity was evaluated following
      intravenous injection using survival as the endpoint. Histopathological,
      immunohistochemical, and electron microscopic evaluation of selected tissues
      revealed the involvement of the expected cell types in the different effector
      systems. Several immunomodulatory drugs--dexamethasone, cyclosporine, liposomal
      muramyltripeptide phosphatidylethanolamine, and SK&F 105685--were evaluated in
      the C. albicans model. Dexamethasone impaired host defense against C. albicans by
      suppressing all endpoints measured. Similarly, cyclosporine showed broad
      immunosuppressive activity, with the exception of yeast uptake from the spleen.
      In contrast, muramyl tripeptide-phosphatidylethanolamine enhanced all but cell
      mediated immunity to C. albicans. SK&F 105685 displayed both stimulatory and
      inhibitory effects on immune responses to the infection. Our studies demonstrate
      that a single organism-based approach can be a useful method for evaluating the
      immunological hazards of drugs on host resistance to infection.

PMID- 9280119
TI  - Experimental model of renal tumors in polycystic kidneys: effects of long-term 2
      amino-4,5-diphenylthiazole administration in rats treated with N-ethyl-N
      hydroxyethylnitrosamine.
AB  - We previously reported that treatment of Fischer-344 rats with 2-amino-4,5
      diphenylthiazole (DPT) results in renal cystic changes. The present study was
      undertaken to examine the effects of long-term DPT treatment after initiation of
      kidney carcinogenesis with N-ethyl-N-hydroxyethylnitrosoamine (EHEN) in Wistar
      rats. One hundred forty-four 6-wk-old male Wistar rats were divided into 6 equal
      receiving groups: 1000 ppm EHEN or normal tap water for 2 wk followed by 1.06%
      DPT or basal diet for the subsequent 14 or 30 wk. Controls were maintained
      without treatment throughout. Subgroups of 6 animals from each group were
      sacrificed after 8, 16, 24, and 32 wk for histopathological assessment of lesion
      development in the kidneys and liver. Animals treated with DPT first developed
      cystic changes of the kidneys (primarily at the corticomedullary border) after 8
      wk of treatment, and these changes progressed with time thereafter. In the groups
      in which DPT treatment was discontinued after 14 wk, cysts then gradually
      decreased in size. All tumors detected in the kidneys were histopathologically
      diagnosed as renal cell adenomas. The tumor multiplicity after 32 wk of treatment
      was significantly higher in Group I, receiving EHEN + DPT for 30 wk (6.33 +/-
      4.46), and Group III, receiving EHEN + DPT for 14 wk (3.83 +/- 1.57), than in
      Group V, EHEN alone (1.00 +/- 0.58) (p < 0.05). Renal cell tumors within cysts
      were only seen in Groups I and III. The general bromodeoxyuridine labeling
      indices for the kidneys at week 32 were significantly higher in Group I (55.94 +/
      21.08 cells/mm2) and Group III (53.75 +/- 12.38 cells/mm2) than in Group V
      (22.38 +/- 6.98 cells/mm2) (p < 0.05). In conclusion, DPT caused cystic changes
      in rat kidneys, which, however, gradually decreased in size after the treatment
      was discontinued, suggesting a reversible nature. DPT clearly also promotes renal
      tumor development after EHEN initiation, and this effect persists, to a certain
      extent, even after the insult is removed.

PMID- 9280120
TI  - Hypertrophy and prolonged DNA synthesis in smooth muscle cells characterize
      pulmonary arterial wall thickening after monocrotaline pyrrole administration to
      rats.
AB  - Monocrotaline pyrrole (MCTP) is a highly reactive pneumotoxic metabolite of the
      pyrrolizidine alkaloid plant toxin monocrotaline. When administered to rats, it
      causes a delayed and progressive lung injury, vascular remodeling, and pulmonary
      hypertension. Structural remodeling consists of endothelial cell swelling
      followed by increased thickness of the vascular media in small pulmonary arteries
      and muscularization of normally nonmuscular arteries. Experiments were performed
      to characterize DNA synthesis and cell proliferation in vascular smooth muscle
      cells (VSMCs) after MCTP and to determine their relationship to changes in the
      thickness of the arterial medial layer of pulmonary resistance vessels. Male
      Sprague-Dawley rats were treated with MCTP (3.5 mg/kg, intravenously) or its
      vehicle (dimethylformamide). To label cells actively synthesizing DNA, rats were
      given the thymidine analog, bromodeoxyuridine (BrdU), 3 times by intraperitoneal
      injection during the 24 hr preceding euthanasia. Using immunohistochemistry, BrdU
      incorporation was quantified as a ratio of labeled nuclei to total nuclei. Within
      5 days after MCTP administration, the thickness of the medial smooth muscle layer
      in arteries 60-250 microm in diameter was increased, prior to evidence of right
      heart hypertrophy. BrdU incorporation by VSMCs in pulmonary arteries was not
      different in vehicle- and MCTP-treated rats for the first 48 hr after treatment.
      However, MCTP caused a significant increase in DNA synthesis in VSMC on days 3-8
      in arteries up to 250 microm in diameter. Although increased DNA synthesis
      precedes cell proliferation, the relative number of medial VSMCs did not increase
      over 8 days, suggesting that hypertrophy alone was responsible for the increased
      thickness of the arterial media. These results demonstrate that MCTP causes
      thickening of the media of pulmonary vessels through VSMC hypertrophy and that
      the prolonged DNA synthesis that accompanies VSMC hypertrophy is not followed by
      proliferation.

PMID- 9280121
TI  - Uranyl nitrate-induced proximal tubule alterations in rabbits: a quantitative
      analysis.
AB  - Naturally occurring uranium in drinking water is a significant health concern in
      several areas of North America. Because the kidney is a known target organ to
      examine the effects of uranium or its compounds, the objective of this study was
      to determine whether kidney repair occurs after exposure to, and withdrawal of,
      uranyl nitrate (UN). This work, part of a larger study to establish safe levels
      of uranium in drinking water supplies, examined the ultrastructural changes in
      proximal tubule cells of New Zealand white rabbits following subchronic exposure
      to UN in water and for 91 days after exposure ended. The rabbit was chosen as the
      experimental animal because of its high sensitivity to uranium. Animals were
      exposed to 24 or 600 mg UN per liter (UN/L) in drinking water for 91 days, with
      no recovery or recovery periods of 45 or 91 days. Ultrastructural changes,
      quantified by a stereological image analysis system based on point counting, were
      observed in renal proximal tubules (PTs). Each electron micrograph was
      statistically considered an experimental unit. The severity of lesions was
      directly proportional to the dose. Animals exposed to 600 mg UN/L had the most
      severe lesions; nevertheless, alterations were remarkable in animals exposed to
      the low dose. At both recovery periods, the lesions were significantly more
      severe than those in animals of the no-recovery group, which may result from the
      kidney's ability to store uranium. The PT cells had increased lysosomal and
      vacuolar mass as well as variations in mitochondrial mass. In addition, there was
      epithelial cell degeneration with a focal loss of brush borders, thickening and
      splitting of tubular basement membrane, and occasionally cell necrosis.
      Interstitial fibrosis of the renal cortex persisted as the recovery period
      increased in the animals of UN-dosed groups. Alterations may be due to disturbed
      fluid transport across the PT and other cells and decreased cell respiration
      resulting from damaged cell constituents. Cell damage caused by UN in drinking
      water persisted throughout the 91-day recovery period. By eventually determining
      the no observable effect level for the kidney by UN, this study may assist in
      devising a model to ascertain the safe levels of uranium in water.

PMID- 9280122
TI  - Histologic lesions associated with intravenous infusions of large volumes of
      isotonic saline solution in rats for 30 days.
AB  - The objective of this study was to characterize the changes associated with
      intravenous infusions of large volumes of isotonic saline solution in rats so
      that effects of the infusion process could be more easily distinguished from
      effects of test articles. Male Sprague-Dawley rats weighing approximately 225-275
      g at the beginning of the study were given intravenous infusions of isotonic
      saline solution once daily for 30 consecutive days at dosages of 40 or 80 ml/kg
      body weight. Saline solution was administered through catheters placed in the
      caudal veins of the tail according to one of the following regimens: 80 ml/kg at
      0.25 ml/min; 80 ml/kg at 0.5 ml/min; 80 ml/kg at 1.0 ml/min; and 40 ml/kg at 1.0
      ml/min. Control rats were catheterized but not administered intravenous fluids.
      One day following the last treatment, all rats were necropsied and major organs
      were collected in 10% formalin. Histologic lesions associated with treatment
      included increased incidence and severity of pulmonary periarterial infiltrates
      of eosinophils, multifocal pulmonary inflammation, pulmonary granulomas that
      often contained hairshaft fragments, endothelial hypertrophy and hyperplasia
      within pulmonary arterial vessels, and pulmonary arterial medial thickening.
      Infiltrates of eosinophils around small pulmonary arteries were more severe in
      rats given intravenous infusions than in untreated rats and were more severe in
      rats given isotonic saline at the 80-ml/kg dosage than at the 40-ml/kg dosage.
      The severity of periarterial infiltrates of eosinophils increased with increasing
      infusion rates in rats that received 80 ml/kg isotonic saline. Pulmonary
      granulomas and multifocal pulmonary inflammation were observed in more rats that
      received intravenous saline than in control rats, but their incidences did not
      appear to vary with the volume or rate of infusion. Multifocal endothelial
      hypertrophy and hyperplasia occurred in most rats given isotonic saline solution
      at all volumes and rates, but not in untreated control rats. Inflammatory lesions
      in the tail near the injection site were considered sequellae of catheter
      insertion that, in some instances, may have been exacerbated by intravenous
      saline infusion. There were no lesions in other organs that were attributable to
      intravenous infusions of isotonic saline solution.

PMID- 9280123
TI  - Relevant exposure to environmental tobacco smoke surrogate does not produce or
      modify secretory otitis media in the rat.
AB  - Parental smoking is a possible risk factor in the development of secretory otitis
      media (SOM) in children. This experiment was designed to determine, using rats as
      an experimental model, whether exposures to environmental tobacco smoke (ETS)
      produce SOM and whether ETS exposure affects the rate of clearance of an
      experimentally induced effusion. Male Sprague-Dawley rats were exposed to 3
      different concentrations of aged and diluted sidestream smoke, a surrogate for
      ETS, from IR4F research cigarettes for 6 hr per day for 5 days. Experimental SOM
      was induced bilaterally in subgroups of animals from each group, by cold air
      exposure to the external auditory canals. Ears of rats were examined during the
      in-life portion of the study. Histopathologic examination of the middle ear was
      conducted at the termination of the 5-day period. The production of SOM was not
      induced by ETS exposure, nor were there differences noted between the groups in
      the rates of clearance of the experimentally induced SOM. Short-term exposure to
      ETS did not affect the acquisition or clearance of SOM in the rat.

PMID- 9280125
TI  - Intraabdominal lymphangiosarcoma in a Fischer-344 rat.
AB  - A Sarcoma arising in the abdominal cavity in an aged Fischer-344 rat was studied
      by immunohistochemistry and electron microscopy. The white-yellow soft mass was
      located on the lumbosacral vertebrae, compressing adjacent parenchymal organs.
      The tumor was made up of spindle shaped cells situated in a background of myxoid
      substance and a small amount of reticulin and collagen fibers. The tumor cells
      grew in a loose storiform pattern and often adhered to each other by their cell
      processes to form ovoid or slitlike spaces. Immunohistochemically, the tumor
      cells were strongly positive for vimentin but negative for keratin, macrophage
      ED1 antigen, alpha-smooth muscle actin, Factor VIII-related antigen, and S100
      protein. Electron microscopy demonstrated the endothelial differentiation of the
      tumor cells, such as occasional luminal spaces, a small number of
      micropinocytotic vesicles, and interdigitating junctions with desmosomes between
      cell processes of adjacent cells. Furthermore, its endothelial origin was
      suggested by the presence of electron-dense rods resembling Weibel-Palade bodies.
      Instead of a definitive basement lamina surrounding the tumor cells, there were
      extracellular thin "anchoring filaments" that were attached to the cell surface
      at areas of increased electron density. These findings indicate that the tumor is
      of lymphatic vessel type rather than blood vessel type.

PMID- 9280124
TI  - Apoptotic cell death of erythrocytes in Xenopus larvae exposed to 2,3,7,8
      tetrachlorodibenzo-p-dioxin.
AB  - Xenopus embryos were exposed to 200 ppb 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) for 5 days from the 2- to 8-cell stage of cleavage to the early larval
      stage. Larvae that developed generalized edema were collected at 7 days after the
      end of TCDD exposure for light and electron microscopic studies. Erythrocytes in
      the peripheral blood of the edematous larvae were examined. Between 0.3 and 33.9%
      of identifiable erythrocytes of exposed larvae had dilated perinuclear cisternae.
      Furthermore, some had extremely condensed nuclear chromatin usually coalesced
      against 1 pole of the nuclear membrane and overall compacted cytoplasm. The
      erythrocytes showing nuclear condensation were phagocytosed by macrophages. These
      features are typical of cells undergoing apoptosis. Anemia is 1 symptom of TCDD
      toxicity in various animal species, including mammals. In this study, we
      demonstrate that TCDD induces apoptotic cell death in circulating erythrocytes of
      Xenopus larvae, which may be 1 cause of anemia in this species.

PMID- 9280126
TI  - HLA-B27 transgenic rats: animal model of human HLA-B27-associated disorders.

PMID- 9280127
TI  - "Have you seen this?" Granular cell uterine tumor in a CD-1 mouse.

PMID- 9280128
TI  - Challenges for editors.

PMID- 9280129
TI  - Veterinary pathology in the United Kingdom.

PMID- 9280130
TI  - Testicular toxicity: regulatory guidelines--the end of formaldehyde fixation?

PMID- 9280131
TI  - Assessment of altered immune status induced by immunomodulatory drugs via an
      apical test in mice.

PMID- 9280132
TI  - Commemoration of the silver anniversary of Toxicologic Pathology and the Society
      of Toxicologic Pathologists.

PMID- 9280133
TI  - A quarter century of Toxicologic Pathology: a personal perspective.

PMID- 9280134
TI  - A personal perspective on the past, present, and future of Toxicologic Pathology.

PMID- 9280135
TI  - Tumor necrosis factor and insulin resistance: specificity of sequence accounts of
      inhibition of insulin action.

PMID- 9280136
TI  - Zinc: an essential and unheralded nutrient.

PMID- 9280137
TI  - The sodium pump and oxidant stress: if only it were so simple.

PMID- 9280138
TI  - Policing function of complement: through the body with gun and camera.

PMID- 9280139
TI  - Regulation of signal transduction through the T cell antigen receptor.
AB  - Considerable work from numerous laboratories has provided important insights into
      the biology of T cell activation. Much has been learned about the most proximal
      signaling events that occur after engagement of the T cell antigen receptor and
      other cell-surface receptors on T lymphocytes. However, our understanding of how
      various signaling pathways are integrated, resulting in cellular proliferation
      and cytokine production or conversely leading to programmed cell death, is far
      from complete. We summarize what is now known about some of the proximal signals
      that result from engagement of the T cell antigen receptor and how some of these
      signals are linked to cellular responses.

PMID- 9280140
TI  - Interactions of parasite and host epithelial cell cycle regulation during
      Pneumocystis carinii pneumonia.

PMID- 9280141
TI  - Identification of specific sites in the TNF-alpha molecule promoting insulin
      resistance in H-411E cells.
AB  - Data from a number of laboratories support a potential role for tumor necrosis
      factor-alpha (TNF-alpha) in the loss of insulin sensitivity and the pathogenesis
      of insulin resistance (IR) in diabetic animal models and human patients. We
      designed experiments to establish a dose-response relationship for TNF-alpha and
      IR in H-411E cells in culture. IR was measured by inhibition of the ability of
      graded amounts of insulin to stimulate expression of calmodulin (CaM) mRNA in
      these cells. This was assessed by autoradiographs of Northern blot(s) of CaM mRNA
      probed with labeled oligonucleotide cDNA for rat CaM. We found that TNF-alpha at
      0.1, 1.0, and 10.0 ng/ml opposed 10,000 microU/ml insulin (i.e., %IR = 20%, 67%,
      and 88%, respectively). At 1.0 ng/ml TNF-alpha, insulin at the concentration of
      1000 microU/ml (0.006 micromol/L) stimulated CaM mRNA at a 41% level and at
      10,000 microU/ml (0.06 micromol/L) at a 63% level. Furthermore, oligopeptide TNF
      alpha homologs (at 1000 x the molar concentration of TNF-alpha) TNF-alpha 69-100
      and TNF-alpha 133-157 conferred 66% and 101% IR, respectively, while all other
      peptide fragments of TNF-alpha were essentially without effect. Studies done with
      both monoclonal and polyclonal antibodies to the TNF-alpha receptor demonstrated
      blocking activity by polyclonal but not by monoclonal anti TNF-alpha receptor
      antibody. This supports the concept that the activity of the peptide fragments
      occurs through the TNF-alpha receptor and not through nonspecific translocation
      across the plasma membrane. These data suggest that the epitopes on TNF-alpha
      that mediate IR reside in two regions of the molecule spanning amino acid
      residues 69-100 and 133-157.

PMID- 9280142
TI  - Decreased expression of CD73 (ecto-5'-nucleotidase) in the CD8+ subset is
      associated with zinc deficiency in human patients.
AB  - We used flow cytometry to observe the changes in T cell populations resulting
      from zinc deficiency in subjects with sickle cell anemia (SCA) and in healthy
      human volunteers without SCA. Zinc deficiency was associated with significant
      decreases in cellular zinc concentration, CD4+/CD8+ ratio, and percentage of
      CD73+ cells in the CD8+ population. The decrease in the percentage of CD73+ cells
      in the CD8+ subset was significantly correlated with lymphocyte zinc
      concentration and was accompanied by essentially no change in the percentage of
      CD11b+ cells in the CD8+ subset. Daily oral zinc supplementation in nine zinc
      deficient human volunteers (25 mg elemental zinc) and in seven zinc-deficient SCA
      subjects (50 mg elemental zinc) resulted in increases in the absolute lymphocyte
      count and significant increases in the CD4+/CD8+ ratio and in the percentage of
      CD73+ cells in the CD8+ subset. In zinc-supplemented subjects, the increase in
      the percentage of CD73+ cells was accompanied by a significant decrease in the
      percentage of CD11b+ cells in the CD8+ subset. Changes in the CD4+/CD8+ and
      CD73+/CD11b- cell ratios in the CD8+ subset after treatment may provide a useful
      diagnostic criterion for zinc deficiency in humans.

PMID- 9280144
TI  - Activation of the alternative pathway of complement by calcium-loaded
      erythrocytes resulting from loss of membrane phospholipid asymmetry.
AB  - The aminophospholipids phosphatidylserine (PS) and phosphatidylethanolamine (PE)
      are exposed on the outer membrane leaflet of deoxygenated and irreversibly
      sickled erythrocytes and senescent normal cells. PS exposure on erythrocytes
      results in the expression of procoagulant activity for the conversion of
      prothrombin to thrombin. Because liposomes or vesicles composed of
      aminophospholipids can activate the alternative pathway of complement, the
      possibility that increased exposure of PS and PE on intact erythrocytes would
      also make them capable of activating the alternative pathway was examined. Loss
      of normal membrane phospholipid asymmetry was induced by incubation of
      erythrocytes with calcium (Ca2+) and the calcium ionophore A23187. PS exposure on
      60% of erythrocytes was confirmed by binding of fluorescein isothiocyanate
      conjugated annexin V. Expression of procoagulant activity, measured with the
      Russell's viper venom clotting assay, was significantly increased on the
      Ca2+/A23187-treated erythrocytes. In addition, the erythrocytes became capable of
      activating the alternative pathway of complement, as judged by an increase in
      cell-bound C3b after incubation with serum and a decrease in alternative pathway
      hemolytic activity of the serum. The effect could be reversed by incubation of
      the Ca2+/A23187-treated erythrocytes under conditions that induced recovery of
      normal membrane phospholipid asymmetry. In contrast, tetrathionate-treated
      erythrocytes showed no increase in binding of annexin V and no procoagulant
      activity and failed to activate the alternative pathway of complement. These
      findings demonstrate that loss of phospholipid asymmetry in erythrocytes not only
      results in expression of procoagulant activity but also renders the cells capable
      of activating the alternative pathway of complement.

PMID- 9280143
TI  - Studies on the mechanism of short-term regulation of pulmonary artery endothelial
      cell Na/K pump activity.
AB  - The Na/K pump is critically important in maintenance of cell homeostasis in the
      face of injury. Little is known about the regulation of endothelial cell Na/K
      pump activity. We previously reported that short-term (30-minute) oxidant-induced
      endothelial cell perturbation increased Na/K-pump activity in intact monolayers
      of bovine pulmonary artery endothelial cells (BPAECs). In this study we
      investigated the mechanism of oxidant-induced increases in endothelial Na/K-pump
      activity, focusing on short-term modulation of alpha1-pump subunit. By using
      immunofluorescence microscopy and confocal scanning laser microscopy, we found
      alpha1 subunit on both apical and basal aspects of BPAECs without polarized
      distribution. Short-term (30-minute) incubation of PAEC monolayers with H2O2 (1
      mmol/L) did not change the relative amounts of alpha1 subunit in membrane
      fractions, as assessed by immunoblotting. Phosphorylation of the alpha1 subunit
      also was not affected by H2O2 treatment. Because protein kinases have been
      reported to alter Na/K-pump activity in several tissues and because H2O2 has been
      reported to increase PKC activity of endothelial cells, we determined the effects
      of inhibition and activation of protein kinase C (PKC) on Na/K-pump activity
      quantitated as ouabain-inhibitable uptake of 86Rb. We also determined the effects
      of PKC activation and inhibition on H2O2-induced increases in Na/K-pump activity.
      Inhibitors of PKC increased Na/K-pump activity over a 30-minute period in intact
      monolayers. Inhibition or depletion of PKC did not prevent H2O2-induced increases
      in pump activity. These results indicate that PKC is an endogenous regulator of
      pulmonary artery endothelial cell Na/K-pump activity but that the effects of H2O2
      are not mediated by activation of PKC or by changes in the expression or
      phosphorylation of alpha1 subunit.

PMID- 9280145
TI  - Red blood cell aggregation in experimental sepsis.
AB  - Red blood cell (RBC) aggregation was investigated in a rat model of sepsis with
      special emphasis on RBC-related factors. Sepsis was produced by cecal
      ligation/puncture, whereas another group had only laparotomy (sham operation);
      blood samples also were obtained from control, unoperated-on animals. RBC
      aggregation was measured in autologous plasma and in 3% dextran 70, 18 hours
      after the operations, by using a Myrenne Aggregometer system and the zeta
      sedimentation ratio (ZSR) method. RBC aggregation in autologous plasma was found
      to be enhanced in both sham-operated and septic animals and was consistent with
      their increased plasma fibrinogen levels. However, RBC aggregation in dextran was
      significantly higher than control only in the sepsis group. RBCs from septic
      animals also aggregated more in septic plasma compared with RBCs from control
      animals. In the sepsis group, RBC deformability was significantly decreased,
      whereas RBC lipid peroxidation was significantly increased. Our results thus
      confirm the known increase of RBC aggregation in septicemia and, in addition,
      demonstrate marked alterations of intrinsic RBC properties that further enhance
      red cell aggregation.

PMID- 9280146
TI  - Platelet-activating factor in plasma of patients with sickle cell disease in
      steady state.
AB  - The role of platelet-activating factor (PAF) in the pathogenesis of microvascular
      vaso-occlusion in sickle cell disease (SCD) is not known. In order to assess a
      role for PAF in vaso-occlusion in patients with SCD in steady state conditions,
      we measured plasma PAF level and plasma PAF acetylhydrolase activity as indices
      of PAF metabolism in vivo. We also studied PAF synthesis, from (3H)-acetate, by
      purified platelets stimulated with A23187. PAF was extracted from plasma of ten
      patients with SCD in steady state and from age-matched controls. PAF, purified by
      thin-layer chromatography, was quantitated by radioimmunoassay. PAF level (mean
      +/- SEM, pg/ml) in plasma of controls was 393 +/- 65, which was significantly
      lower than the 797 +/- 62 measured in plasma of patients with SCD. There was no
      difference in acetylhydrolase activity between the two groups. PAF synthesis
      (mean +/- SEM, nmol/10(6) cells) by platelets of controls without exogenous lyso
      PAF was 1.69 +/- 0.24, higher than the 0.59 +/- 0.038 synthesized by platelets of
      patients with SCD. Incubation of platelets with 1.0 micromol/L lyso-PAF increased
      PAF synthesis by controls to 8.93 +/- 1.76, still higher than the 4.59 +/- 0.98
      synthesized by platelets of patients with SCD. Our data show that patients with
      SCD are susceptible to a higher circulating levels of PAF in vivo during steady
      state conditions. We speculate that higher levels of PAF may be a contributing
      factor to the persistent stress and inflammatory state of the microcirculation of
      patients with SCD.

PMID- 9280147
TI  - Ascorbic acid deficiency in porphyria cutanea tarda.
AB  - Porphyria cutanea tarda (PCT), the most common form of porphyria, is manifested
      as skin photosensitivity caused by excess hepatic production of uroporphyrin and
      heptacarboxylporphyrin. In experimental animal models, ascorbic acid modulates
      chemically induced uroporphyrin accumulation. The purpose of this study was to
      determine whether ascorbic acid is decreased in the plasma of patients with PCT.
      Plasma was obtained after an overnight fast from 21 PCT patients, 16 of whom were
      infected with hepatitis C virus (HCV), and from a separate group of 9 patients
      with HCV infection but not PCT. Thirteen PCT patients were studied when they had
      active disease and 8 after treatment-induced remission. Plasma ascorbic acid was
      low (<23 micromol/L) in 11 (85%) of the 13 untreated PCT patients and deficient
      (<11 micromol/L) in 8 (62%). Two patients with normal ascorbic acid levels (45
      and 62 micrommol/L) had consumed multivitamins. In 2 patients with deficient
      ascorbic acid, plasma levels returned to normal after phlebotomy treatment. Of
      the 8 patients studied during remission, 4 had normal ascorbic acid values and 4
      were deficient (5 to 8 micromol/L). Plasma ascorbic acid values were normal for
      all patients who had HCV but no PCT. These data suggest that plasma ascorbic acid
      concentrations are commonly low in PCT, but this decrease is unrelated to HCV
      infection. Ascorbic acid deficiency may be one of the factors that contributes to
      the pathogenesis of PCT.

PMID- 9280148
TI  - Activated protein C resistance phenotype in patients with antiphospholipid
      antibodies.
AB  - The effect of antiphospholipid antibodies (aPL) on the action of activated
      protein C (APC) was examined in 32 patients: 19 with lupus anticoagulant (LA), 6
      with anticardiolipin antibodies (aCL), and 7 with LA and aCL. Eighteen patients
      had a ratio of activated partial thromboplastin time (APTT) with APC to APTT
      without APC (APTT ratio) <2.06 (cut-off level) and no factor V Leiden mutation;
      these patients showed APC-resistance (APC-R) phenotype. The mean prolongation of
      APTT after addition of APC in a control group was 45.3 seconds, with a lower
      limit of 31.4 seconds. Only 3 of the 18 patients with low APTT ratio had a
      prolongation of <31.4 seconds; they were classified as true APC-R phenotype,
      whereas the other 15 patients were classified as spurious APC-R. Of the 3
      patients with true APC-R, 2 had deep venous thrombosis, 1 with pulmonary
      embolism, and the third had recurrent abortion. Of the other 15 patients, 2 had
      had ischemic stroke, 1 had recurrent abortion, and 12 were asymptomatic.
      Circulating APC level was measured in 14 of the 18 aPL patients with a low APTT
      ratio; it was lower than the normal lower limit in 4 patients and within the
      lower limit in 2. Three of the 4 patients with reduced APC levels had a history
      of thrombosis. We conclude that patients with aPL who show APC-R phenotype due to
      a low APTT ratio without the factor V Leiden mutation can be classified into two
      groups: true and spurious APC-R phenotype. Since those with true APC-R phenotype
      could have greater thrombotic risk, adequate classification of these patients is
      important. Moreover, aPL can sometimes interfere with the activation of protein
      C, thus reducing the circulating levels of APC, and this could constitute another
      thrombotic risk factor.

PMID- 9280149
TI  - Cyclic tensile stretch on bovine articular chondrocytes inhibits protein kinase C
      activity.
AB  - Osteoarthrosis, a common pathway of joint deterioration, is caused by mechanical
      stress loaded on articular cartilage. We previously demonstrated the involvement
      of protein kinase C (PKC) in the development of osteoarthritis in vitro. In this
      study, we examined the effect of mechanical stress on chondrocyte metabolism and
      the activity of PKC in vitro. Low frequency and magnitude of cyclic tensile
      stretch loaded on chondrocytes increased proteoglycan synthesis. However, high
      frequency and magnitude of stress decreased its synthesis. In this condition,
      activity of PKC was reduced. These results suggest an involvement of PKC in the
      stress-mediated inhibition of proteoglycan synthesis.

PMID- 9280150
TI  - Modulatory effects of the colonic milieu on neutrophil oxidative burst: a
      possible pathogenic mechanism of ulcerative colitis.
AB  - An important hallmark of ulcerative colitis (UC) is mucosal neutrophil (PMN)
      infiltration associated with mucosal damage. This suggests that colonic
      chemoattractants such as bacterial products (e.g., N-formyl-methionyl-leucyl
      phenylalanine (fMLP), lipopolysaccharide (LPS)) reach systemic circulation and
      attract PMNs to the colon. PMNs are then activated in the colonic mucosa and
      release their toxic oxidative metabolites. However, bacterial products are also
      present in the systemic circulation of healthy subjects. Thus we hypothesized
      that PMNs develop tolerance to colonic factors in the normal state and that this
      tolerance is absent in UC. We evaluated the PMN respiratory burst in response to
      stimulation with fMLP, LPS, or phorbol 12-myristate 13-acetate (PMA) by measuring
      the production of reactive oxygen species (ROS) with both luminol-enhanced
      chemiluminescence and a cytochrome C reduction assay. PMNs were obtained from
      control subjects, inactive UC patients, patients with UC who had undergone
      colectomies, and non-UC patients with colectomies. All three stimuli induced a
      significant rise in ROS. PMNs from non-UC colectomy subjects produced
      significantly higher ROS than PMNs from control subjects with intact colons in
      response to both fMLP and LPS. In contrast, PMNs from UC colectomy patients
      produced levels of ROS similar to those produced by PMNs from UC patients with
      intact colons in response to fMLP and LPS. Colectomy had no effect on PMA-induced
      ROS production in controls. The observed difference in fMLP-induced ROS
      production in control subjects with intact colons was not due to fMLP receptor
      down-regulation because a competition assay performed with the fMLP blocker BMLP
      showed a similar receptor apparent affinity in all four groups. We conclude the
      following: (1) the normal colonic milieu modulates the PMN respiratory burst,
      resulting in hyporesponsiveness of PMNs to "physiologic" but not "pharmacologic"
      stimulation. This effect is not due to receptor down-regulation. (2) UC colonic
      milieu does not appear to modulate PMN respiratory burst. This loss of PMN
      "tolerance" to colonic factors may have a pathogenic role in the sustained
      inflammation and tissue damage in UC.

PMID- 9280152
TI  - Osteoarthritis/osteoarthrosis.

PMID- 9280151
TI  - Lack of major hypoxia and significant brain damage in rats despite dramatic
      hyponatremic encephalopathy.
AB  - Brain myelinolysis could complicate the excessive correction of chronic
      hyponatremia. Recently it was suggested that hypoxia rather than correction of
      hyponatremia would be responsible for myelinolysis. We analyzed the incidence and
      the severity of potentially associated hypoxia and its consequences on survival
      and on the development of brain damage in rats in which major hyponatremic
      encephalopathy had developed after either pure acute hyponatremia (serum sodium
      concentration: -40 mEq/L/3 hr, group I, n = 8) or acute hyponatremia (serum
      sodium concentration: -30 mEq/L/3 hr, group II, n = 12) superimposed on chronic
      hyponatremia of 3 days' duration (serum sodium concentration: 113 mEq/L). Our
      study revealed the following: (1) Despite dramatic hyponatremic encephalopathy
      (convulsions, coma), hypoxia (PO2 < 70 mm Hg) was present, but the PO2 was not
      decreased below 40 mm Hg. All of these rats died rapidly if they remained
      hyponatremic. (2) In the animals rescued by NaCl, the incidence of brain
      myelinolysis was low (10%), whatever the duration (pure acute or chronic plus
      acute) of the hyponatremia and despite the combination of hypoxia with major
      hyponatremic encephalopathy. (3) When acute hyponatremia is superimposed on a
      chronic preexisting hyponatremic state, the acute component of serum sodium
      concentration decrease could be rapidly corrected (serum sodium concentration:
      +35 mEq/L/21 hr) without fear of permanent brain damage. Our results suggest that
      even in the presence of dramatic hyponatremic encephalopathy and associated
      hypoxia, neuropathologic sequelae are uncommon. Brain lesions related to post
      anoxic encephalopathy probably develop only after respiratory arrest occurs.

PMID- 9280153
TI  - Increased prevalence of the seven-repeat variant of the dopamine D4 receptor gene
      in patients with obsessive-compulsive disorder with tics.
AB  - The polymorphism characterized by a varying number of 48 bp repeats (VNTR) in the
      dopamine D4 receptor (DRD4) gene was examined in 61 obsessive-compulsive disorder
      (OCD) probands with and without tics. Most of the OCD patients with tics showed
      at least one copy of the 7-fold variant compared to those affected subjects
      without tics (91 vs. 48%, respectively, Yates corrected chi2 = 5.54, P = 0.018).
      Similarly, a higher number of copies of this common variant were detected in the
      group of probands displaying tics compared to those OCD's without tics (Yates
      corrected chi2 = 4.66, P = 0.03). Our study suggests that the seven-repeat allele
      of the DRD4 gene could be a factor in the phenotypic variance of tics among OCD
      individuals.

PMID- 9280154
TI  - Modulation of hippocampal acetylcholine release after fimbria-fornix lesions and
      septal transplantation in rats.
AB  - Female Long-Evans rats sustained electrolytic lesions of the fimbria and the
      dorsal fornix causing a partial lesion of the septohippocampal pathway. Two weeks
      later, the rats received intra-hippocampal grafts of fetal septal cell
      suspensions. Nine to twelve months later, the release of acetylcholine (ACh) in
      the hippocampus of sham-operated, lesion-only and grafted rats was measured by
      microdialysis. The extent of cholinergic (re)innervation was determined by
      acetylcholinesterase (AChE) staining and densitometry. In both lesion-only and
      grafted rats, the ratio of ACh release to AChE staining intensity was increased
      as compared to sham-operated rats, indicating a loss of endogenous inhibitory
      mechanisms. Scopolamine (0.5 mg/kg i.p.), a muscarinic antagonist, increased ACh
      release in all treatment groups. 8-OH-DPAT (0.5 mg/kg s.c.), an agonist at
      serotonergic 5HT1A-receptors, induced an increase of hippocampal ACh release in
      sham-operated rats. This effect was lost in lesion-only rats, but was fully
      restored by neuronal grafting. As 8-OH-DPAT influences hippocampal ACh release by
      a postsynaptic action, this finding indicates that the host brain exerts a
      serotonergic influence on the grafted cholinergic neurons.

PMID- 9280155
TI  - p75 neurotrophin receptor immunoreactivity in the aged human hypothalamus.
AB  - Low-affinity p75 neurotrophin receptor (p75NTR) immunoreactivity in the aged
      human hypothalamus was examined in autopsied material. Numerous p75NTR
      immunoreactive cells were found in the paraventricular and supraoptic
      hypothalamic nuclei. The suprachiasmatic nucleus was devoid of p75NTR
      immunostaining. Many p75NTR-immunoreactive fibers extended laterally and
      ventrally from the paraventricular and supraoptic nuclei into the pituitary stalk
      and median eminence. Our results suggest that neurotrophins may be present within
      the human hypothalamo-hypophyseal system.

PMID- 9280156
TI  - Bicuculline methiodide potentiates NMDA-dependent burst firing in rat dopamine
      neurons by blocking apamin-sensitive Ca2+-activated K+ currents.
AB  - Apamin, a bee venom toxin which blocks a Ca2+-dependent K+ current, potentiates N
      methyl-D-aspartate (NMDA)-induced burst firing in dopamine neurons. We now report
      that burst firing is also potentiated by an apamin-like effect of bicuculline
      methiodide (BMI) at the same concentration (30 microM) which blocks GABA(A)
      receptors in vitro. Using microelectrodes to record intracellularly from rat
      dopamine neurons in the midbrain slice, BMI reduced the apamin-sensitive
      afterhyperpolarization in all cells tested. BMI also mimicked apamin (100 nM) by
      potentiating burst firing produced by a concentration of NMDA (10 microM) which
      is too low to evoke burst firing when perfused alone. When recording under
      voltage-clamp, both BMI and apamin reduced a depolarization-activated outward
      current which was also sensitive to perfusate containing no-added Ca2+. Although
      picrotoxin (100 microM) and bicuculline free base (30 microM) blocked the
      inhibition of firing produced by the GABA(A) agonist isoguvacine (100 microM),
      neither had apamin-like effects. We conclude that BMI potentiates burst firing by
      blocking an apamin-sensitive Ca2+-activated K+ current.

PMID- 9280157
TI  - Hydrogen peroxide is selectively toxic to immature murine neurons in vitro.
AB  - Hydrogen peroxide (H2O2) accumulates during hypoxic-ischemic brain injury and may
      mediate neurotoxicity in the immature brain. To determine whether H2O2 causes
      maturation specific neurotoxicity, primary neuronal cultures were exposed to H2O2
      (25, 50, 100 microM) for 5 min or 24 h during in vitro development, and toxicity
      was assessed. Immature neurons incurred marked and dose dependent injury after
      both brief and prolonged H2O2 exposures, and marked dose dependent death
      following prolonged H2O2 exposures. Mature neurons incurred marked injury
      following prolonged but not brief H2O2 exposures, and were relatively resistant
      to H2O2 induced death following both brief and prolonged exposures. Thus, H2O2 is
      selectively toxic to immature neurons in vitro. Neuronal vulnerability to H2O2
      during in vivo development is unknown and warrants investigation.

PMID- 9280158
TI  - Neurotensin and dopamine D2 activation oppositely regulate the same K+
      conductance in rat midbrain dopaminergic neurons.
AB  - Midbrain dopaminergic neurons are excited by neurotensin (NT) and inhibited by
      dopamine. Interactions between these neurotransmitters have been reported, but no
      interaction has yet been identified at the level of ionic and signal transduction
      mechanisms. Using the whole-cell clamp technique, we examined the interaction of
      NT and quinpirole (QUIN) (a dopamine D2 agonist) on midbrain ventral tegmental
      area neurons cultured from the rat. We found that NT could inhibit the K+
      conductance induced by QUIN. By interrupting normal signal transduction with the
      non-hydrolyzable GTP analogue GTPgammaS, we found that this interaction occurred
      downstream of the membrane neurotransmitter receptors. Similar interactions were
      observed between QUIN and tachykinin or metabotropic glutamate agonists.

PMID- 9280159
TI  - Lipopolysaccharide rapidly activates K+ channels at the intracellular membrane
      face of rat cerebral artery smooth muscle cells.
AB  - Lipopolysaccharide (LPS) may accumulate inside mammalian cells through
      endocytotic uptake or during the replication in invasive bacterial strains.
      However, the effects of intracellular LPS on cell function remain unknown. This
      study therefore examined the action of intracellularly applied E. coli LPS on
      large-conductance, Ca2+-dependent K+ channels (BK channels) in the membrane of
      rat cerebrovascular smooth muscle cells (CVSMCs). LPS (10-100 microg/ml) rapidly
      increased the open probability of BK channels when applied to the cytoplasmic
      face of CVSMC membrane patches. This response was reversible, dose-dependent and
      reflected an enhanced rate of channel opening in the presence of LPS. These
      results show for the first time that LPS can alter the gating behavior of ionic
      channels when applied to the cytoplasmic face of a eukaryotic cell membrane.

PMID- 9280160
TI  - Concurrent elevation of the levels of expression of striatal preproenkephalin and
      preprodynorphin mRNA in the rat brain by chronic treatment with caffeine.
AB  - Caffeine is a widely consumed substance that elicits psychomotor stimulant
      effects and also displays addictive properties. In order to assess the effect of
      caffeine on striatal neuropeptide mRNA expression, male rats were injected (i.p.)
      with caffeine at 20, 40 or 80 mg/kg of body weight twice daily for 9 consecutive
      days. Preproenkephalin (PPE), preprotachykinin A (PPT-A) and preprodynorphin
      (PPD) mRNA levels were determined in coronal sections of brain tissue by in situ
      hybridization histochemistry. PPE mRNA levels were increased by chronic caffeine
      in all subdivisions of the striatum at 80 mg/kg (dorsolateral caudate-putamen
      (dlCPu), +139%; dorsomedial CPu (dmCPu), +42%; ventrolateral CPu (vlCPu), +102%;
      ventromedial CPu (vmCPu), +20%; and anterior CPu (aCPu), +75% relative to vehicle
      injected controls that were normalized to 0% change). Similarly, PPD mRNA
      expression was increased in all aspects of the striatum at 80 mg/kg (dlCPu,
      dmCPu, vlCPu, vmCPu and aCPu, +98%, +25%, +104%, +9% and +85%, respectively). In
      contrast to PPE mRNA, PPD mRNA was increased +117% above control in the nucleus
      accumbens (NAc) at 20 mg/kg of caffeine. PPT-A mRNA expression was not
      significantly affected by caffeine treatment in the CPu or NAc. The data
      demonstrate that repeated exposure to caffeine selectively increases opioid
      neuropeptide mRNA expression in the striatum and the NAc of the rat brain by a
      dopamine-independent mechanism.

PMID- 9280161
TI  - Coexpression of heat-evoked and capsaicin-evoked inward currents in acutely
      dissociated rat dorsal root ganglion neurons.
AB  - Noxious heat is able to activate heat-sensitive nociceptors in the skin very
      rapidly, but little is known about the mechanisms by which heat is transduced. We
      used the whole-cell patch-clamp technique to study the effects of noxious heat
      and capsaicin on freshly dissociated rat dorsal root ganglion neurons in vitro.
      Using temperatures between 41 degrees C and 53 degrees C, 8 of 19 small neurons
      (phi < or = 30 microm) exhibited a heat-evoked inward current. All heat-sensitive
      neurons tested were also capsaicin-sensitive. Moreover, the heat response tended
      to be enhanced after capsaicin (360 +/- 150 pA versus 125 +/- 45 pA, P < 0.1, n =
      7). Two of five heat-insensitive neurons were excited by capsaicin; both neurons
      developed a heat response after capsaicin. Large neurons (phi > 30 microm) did
      not respond to heat (0/7), and were not sensitive to capsaicin either. These
      findings indicate that heat stimuli may directly activate capsaicin-sensitive
      primary nociceptive afferents.

PMID- 9280162
TI  - Amelioration of brain edema by topical application of glial cell line-derived
      neurotrophic factor in reperfused rat brain.
AB  - Glial cell line-derived neurotrophic factor (GDNF) was applied topically on the
      brain surface of reperfused rat brain after 90 min of transient middle cerebral
      artery occlusion. In contrast to the cases treated with vehicle, a formation of
      brain edema was greatly reduced at 2 days by the treatment with GDNF. Terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling
      (TUNEL) staining was also markedly reduced in the cases with GDNF treatment both
      at 1 and 2 days of reperfusion. However, amelioration of the induction of
      immunoreactive 70 kDa heat shock protein was only a minimum by the GDNF
      treatment. The present results suggest that the treatment with GDNF has a
      significant effect on ameliorating brain edema formation after transient focal
      brain ischemia, and the effect is greatly associated with the reduction of TUNEL
      staining, but minimally with that of stress response of cells.

PMID- 9280163
TI  - Acute effects of tetrahydrobiopterin on the dynamic characteristics and
      adaptability of of vestibulo-ocular reflex in normal and flocculus lesioned
      rabbits.
AB  - The acute effects of (6R)-5,6,7,8-tetrahydro-L-biopterin (R-THBP) on the dynamic
      characteristics of horizontal vestibulo-ocular reflex (HVOR) were examined in
      chronically prepared alert pigmented rabbits. The HVOR gain was measured by 10
      degrees-0.1 Hz sinusoidal oscillation of the turntable in darkness. In control
      rabbits, intramuscular injection of R-THBP (10 mg/kg) induced an increase of HVOR
      gain by 0.1-0.2, which lasted for 1-3 h. Sustained 10 degrees-0.1 Hz sinusoidal
      oscillation of the turntable and screen in the reversed direction induced an
      adaptive increase of HVOR gain by 0.2 in 3 h, which was not affected by
      applications of R-THBP. In flocculus lesioned rabbits, the HVOR gain reduced by
      23%, and applications of R-THBP no longer induced a HVOR gain increase. These
      experimental observations suggested that the R-THBP affected on the HVOR dynamics
      within the cerebellar flocculus or its related neural areas.

PMID- 9280164
TI  - Changes in NADPH diaphorase reactivity and neuronal nitric oxide synthase in the
      rat retina following constant illumination.
AB  - The distribution of nicotinamide adenine dinucleotide phosphate diaphorase
      (NADPHd) reactivity and neuronal nitric oxide synthase immunoreactivity (nNOS-IR)
      was investigated in the rat retina during photoreceptor regeneration.
      Photoreceptor damage and the disappearance of a NADPHd reactive/nNOS-IR band
      corresponding to inner photoreceptor segments were observed after continuous
      exposure to light irradiation. Both events were reversible after 20 days of total
      darkness. Also a progressive decrease in the number and in the staining intensity
      of NADPHd reactivity in amacrine cells were found along the first 3-6 days of
      darkness stabilizing thereafter in both illuminated and control groups. However,
      staining intensity in the former group remained more elevated than in the latter
      one. NOS activity in the retina varies depending on functional and pathological
      states.

PMID- 9280165
TI  - Human brain potentials observed using the line-motion method: the
      neurophysiological correlates of visual illusory motion perception.
AB  - This study shows the temporal dynamics of neurophysiological activities in
      illusory motion perception. Event-related brain potentials were recorded from 12
      healthy subjects while they performed a two-alternative (motion/no motion),
      forced-choice task using the line motion method. Amplitudes of a late positive
      component at Fz, Cz, Pz, O1 and O2 increased as cue lead time (CLT) increased. At
      a CLT of 50 ms, the amplitudes of the late positive component (the peak latency
      at O1, O2: 310 ms; Fz, Cz, Pz: 360-390 ms) observed during illusory motion
      perception was larger than that observed during no motion perception, even though
      the physical stimuli were the same. These results suggest that the perception of
      illusory motion correlates to a relatively late stage of visual information
      processing.

PMID- 9280166
TI  - Apolipoprotein E epsilon2 allele and early onset schizophrenia.
AB  - To explore the role of apolipoprotein E (ApoE) in schizophrenia, we investigated
      ApoE phenotypes in a group of patients with schizophrenia. Serum samples were
      obtained from 122 schizophrenic patients and 126 controls in Japan and were
      examined using isoelectric focusing/immunoblotting. This experiment showed a
      trend toward a decreased frequency of ApoE epsilon4 in schizophrenia and no link
      between ApoE epsilon4 and familial schizophrenia or early onset schizophrenia. On
      the other hand, a decreased frequency of ApoE epsilon2 in early onset
      schizophrenia was detected. These results suggest that ApoE epsilon2 protects
      against early onset schizophrenia, and that ApoE epsilon4 is not involved in the
      development of schizophrenia in Japanese.

PMID- 9280167
TI  - No association between alpha1-antichymotrypsin polymorphism, apolipoprotein E and
      patients with late-onset Alzheimer's disease.
AB  - Apolipoprotein E (APOE) has been identified as a major susceptibility marker for
      Alzheimer's disease (AD) and it has been proposed that a common polymorphism in
      the alpha1-antichymotrypsin (ACT) gene increases the risk of developing AD, when
      the combination of ACT/AA genotype and APOE epsilon4 allele segregate together.
      The ACT polymorphism was analysed in 218 sporadic late-onset AD patients and 101
      healthy control subjects from Eastern Finland. Samples of the ACT polymorphism
      were divided into three subgroups according to their APOE genotypes and the
      genotyping of samples was done using the polymerase chain reaction (PCR) method.
      Any association between the AD group and the controls was tested with the chi2
      test. Our data failed to detect any effect of polymorphism in the ACT genotypes
      associated with the APOE alleles, suggesting that in this population ACT does not
      increase the risk of AD.

PMID- 9280168
TI  - Apolipoprotein-E genotype in normal aging, age-associated memory impairment,
      Alzheimer's disease and vascular dementia patients.
AB  - Apolipoprotein-E (Apo-E) genotype and allele frequencies were evaluated in
      patients with late-onset probable Alzheimer's disease (LOAD; n = 64), early-onset
      probable Alzheimer's disease (EOAD; n = 32), possible Alzheimer's disease (pAD; n
      = 44), vascular dementia (VD; n = 12), age-associated memory impairment (AAMI; n
      = 15) and 40 healthy age-matched controls. APO-E was performed by polymerase
      chain reaction products digested by the restriction enzyme HhaI. A statistically
      significant increase of epsilon4 frequency was found in LOAD as compared to the
      other groups, and in pAD with respect to controls, while VD and AAMI groups did
      not disclose any difference as regards to control subjects. Multivariate analysis
      showed a significant association of epsilon4 with female gender. Our results
      confirm the increased frequency of epsilon4 in both probable and possible LOAD,
      failing to show a similar trend in VD and AAMI.

PMID- 9280169
TI  - Resting metabolic rate in obese, premenopausal black women.
AB  - In the United States, obesity is more prevalent in black than in non-Hispanic
      white women. Because low resting metabolic rate (RMR) has been suggested as a
      risk factor for weight gain, we compared RMR in 22 black and 20 white obese [body
      mass index (BMI; in kg/m2) range: 28.9-48.6 and 26.9-44.1, respectively], weight
      stable, premenopausal, nondiabetic women. RMR was measured on two or three
      different occasions within a 1-wk period. The black and white groups did not
      differ significantly in age, degree of fitness, BMI, fat mass, or fat-free mass
      (FFM). In each group, RMR was predicted independently by FFM but not by age,
      degree of fitness, body fat mass, or body fat distribution. The slopes of the
      equations predicting RMR from FFM in black and white groups were not
      significantly different. However, the black women had significantly lower RMRs
      than the white women after adjustment for FFM measured by five body-composition
      models: dual-photon X-ray absorptiometry (DXA), hydrodensitometry, total body
      water, a three-compartment model, a four-compartment model, as well as for the
      absolute total-body potassium content as a measure of metabolically active FFM.
      By each analysis, the black women had significantly lower (P < 0.01) FFM-adjusted
      RMR than the white women; this difference ranged from 671 to 889 kJ/d depending
      on the body-composition method used to estimate FFM. This could contribute to the
      difference in the prevalence of obesity in the populations represented by these
      groups.

PMID- 9280170
TI  - Ad libitum intake of a high-carbohydrate or high-fat diet in young men: effects
      on nutrient balances.
AB  - The effect of diet composition [high-carbohydrate, low-fat (HC) and high-fat, low
      carbohydrate (HF) diets] on macronutrient intakes and nutrient balances was
      investigated in young men of normal body weight. Eleven subjects were studied on
      two occasions for 48 h in a whole-body indirect calorimeter in a crossover
      design. Subjects selected their meals from a list containing a large variety of
      common food, which had a food quotient > 0.85 for the HC diet and < 0.85 for the
      HF diet. The average ad libitum intake was 14.41 +/- 0.85 MJ/d (67%, 18%, and 15%
      of energy as carbohydrate, fat, and protein, respectively) with the HC diet and
      18.25 +/- 0.90 MJ/d (26%, 61%, and 13% of energy as carbohydrate, fat, and
      protein, respectively) with the HF diet. Total energy expenditure was not
      significantly influenced by diet composition: 10.46 +/- 0.27 and 10.97 +/- 0.22
      MJ/d for the HC and HF diets, respectively. During the 2 test days, cumulative
      carbohydrate storage was 418 +/- 72 and 205 +/- 47 g, and fat balance was 29 +/-
      17 and 291 +/- 29 g with the HC and HF diets, respectively. Only the HF diet
      induced a significantly positive fat balance. These results emphasize the
      important role of the dietary fat content in body fat storage.

PMID- 9280172
TI  - How much physical activity is needed to minimize weight gain in previously obese
      women?
AB  - Exercise is frequently identified as a predictor of weight maintenance after
      elective weight loss in retrospective studies of treatments for obesity. We
      conducted a prospective study to test whether physical activity measured soon
      after weight loss predicted weight maintenance and to determine how much physical
      activity was required to optimize maintenance. Thirty-two women [mean (+/- SD)
      age, 38 +/- 7 y; body mass index (in kg/m2), 24 +/- 3] were recruited through
      local advertising within 3 mo of reaching their target for weight loss (23 +/- 9
      kg). Total energy expenditure (TEE) was measured by the doubly labeled water
      method. Postabsorptive resting metabolic rate (RMR) and postprandial RMR
      [expressed as thermic effect of a meal (TEM)] were measured by respiratory gas
      exchange. Women in the physically active group (ratio of TEE to RMR = 1.89 +/-
      0.08) gained 2.5 +/- 3.1 kg during the 12 mo after reaching their target for
      weight loss, moderately active women (TEE:RMR = 1.64 +/- 0.05) gained 9.9 +/-
      10.5 kg, and sedentary women (TEE:RMR = 1.44 +/- 0.08) gained 7.0 +/- 5.9 kg (P <
      0.01). Retrospective analyses of weight regain as a function of energy expended
      in physical activity indicated a threshold for weight maintenance of 47 kJ x kg
      body wt(-1) x d(-1). This corresponds to an average of 80 min/d of moderate
      activity or 35 min/d of vigorous activity added to a sedentary lifestyle.

PMID- 9280171
TI  - Hypoenergetic nutrition support in hospitalized obese patients: a simplified
      method for clinical application.
AB  - Nutrition support in obese hospitalized patients is controversial, with some
      practitioners advocating restricted energy or hypoenergetic feedings when
      patients are being actively treated for another disease. To eliminate the need
      for indirect calorimetry, this randomized, double-blind, prospective study was
      undertaken to determine whether obese hospitalized patients given a hypoenergetic
      parenteral regimen administered to provide 2 g protein x kg ideal body wt (IBW)(
      1) x d(-1), could achieve nitrogen balance comparable with that of control
      subjects given isonitrogenous normoenergetic formula. Thirty obese hospitalized
      patients with an average body mass index (BMI; in kg/m2) of 35 were randomly
      assigned to the hypoenergetic [energy (kJ):nitrogen (g) = 314:1; energy
      (kcal):nitrogen (g) = 75:1; n = 16] or control [energy (kJ):nitrogen (g) = 628:1;
      energy (kcal):nitrogen (g) = 150:1; n = 14] formulas. The initial formula volume
      administered provided 2 g protein x kg IBW(-1) x d(-1). Nitrogen balance was
      determined on day 0 and weekly. The total daily energy intake [per kg actual body
      weight (ABW)] was 57 +/- 12 kJ (hypoenergetic) compared with 94 +/- 21 kJ
      (control), P < 0.001, and the nonprotein energy intake was 36 +/- 10 kJ
      (hypoenergetic) compared with 73 +/- 17 kJ (control), P < 0.001. Protein intake
      was the same per ABW, 2.0 +/- 0.2 and 2.0 +/- 0.1 g kg IBW(-1) x d(-1), NS, for
      the hypoenergetic and control formulas, respectively. Mean net nitrogen balance
      was not significantly different between the groups, even after patients were
      subgrouped by illness, nor was the percentage of patients achieving positive
      nitrogen balance. Duration of treatment averaged 10.5 +/- 2.6 d. Weight change
      did not differ significantly between groups. These data indicate that patients
      receiving hypoenergetic feedings providing 2 g protein x kg IBW(-1) x d(-1)
      achieved nitrogen balance comparable with patients given conventional total
      parenteral nutrition regimens, even when critically ill.

PMID- 9280173
TI  - Effects of strength or aerobic training on body composition, resting metabolic
      rate, and peak oxygen consumption in obese dieting subjects.
AB  - Given that resting metabolic rate (RMR) is related largely to the amount of fat
      free mass (FFM), the hypothesis was that strength training, which stimulates
      muscle hypertrophy, would help preserve both FFM and RMR during dieting. In a
      randomized controlled intervention trial, moderately obese subjects (aged 19-48
      y) were assigned to one of three groups: diet plus strength training, diet plus
      aerobic training, or diet only. Sixty-five subjects (25 men and 40 women)
      completed the study. They received a formula diet with an energy content of 70%
      of RMR or 5150 +/- 1070 kJ/d (x +/- SD) during the 8-wk intervention. They were
      seen weekly for individual nutritional counseling. Subjects in the two exercise
      groups, designed to be isoenergetic, trained three times per week under
      supervision. Those in the strength-training group performed progressive weight
      resistance exercises for the upper and lower body. Those in the aerobic group
      performed alternate leg and arm cycling. After 8 wk, the mean amount of weight
      lost, 9.0 kg, did not differ significantly among groups. The strength-training
      group, however, lost significantly less FFM (P < 0.05) than the aerobic and diet
      only groups. The strength-training group also showed significant increases (P <
      0.05) in anthropometrically measured flexed arm muscle mass and grip strength.
      Mean RMR declined significantly, without differing among groups. Peak oxygen
      consumption increased the most for the aerobic group (P = 0.03). In conclusion,
      strength training significantly reduced the loss of FFM during dieting but did
      not prevent the decline in RMR.

PMID- 9280174
TI  - Vitamin A status during the third trimester of pregnancy in Spanish women:
      influence on concentrations of vitamin A in breast milk.
AB  - We examined the relation between the vitamin A status of Spanish women during
      pregnancy and concentrations of vitamin A in breast milk. The subjects were 57
      healthy, lactating women aged 18-35 y. Vitamin A intake was determined during the
      third trimester of pregnancy by using a 5-d dietary record that included a Sunday
      and by recording the quantities provided by supplements. HPLC was used to
      determine vitamin A concentrations in subjects' serum during the third trimester,
      in transitional breast milk (on days 13-14 of lactation), and in mature breast
      milk (on day 40). During the third trimester, 33.3% of subjects had vitamin A
      intakes from diet and supplements < 800 microg/d, the recommended value. These
      subjects had serum and breast milk vitamin A concentrations that were
      significantly lower than those of subjects who consumed greater quantities of the
      vitamin. Furthermore, subjects with serum vitamin A concentrations < 1.05
      micromol/L during the third trimester (22.8%) had lower mean (+/- SD)
      concentrations of the vitamin in mature breast milk than did subjects with higher
      serum concentrations (1.8 +/- 1.2 micromol/L compared with 2.6 +/- 0.8
      micromol/L; P < 0.05). These results show that vitamin A intake and serum vitamin
      A concentrations during pregnancy influence the composition of breast milk. Given
      that 12.3% of subjects had < 1.40 micromol vitamin A/L in mature breast milk, it
      seems advisable to follow and, if necessary, improve vitamin A status during
      pregnancy and lactation.

PMID- 9280175
TI  - Intake and indicators of iron and zinc status in children consuming diets low in
      saturated fat and cholesterol: the STRIP baby study. Special Turku Coronary Risk
      Factor Intervention Project for Babies.
AB  - A low-fat diet may predispose children to low meat consumption, low iron intake,
      and iron deficiency. In the randomized prospective Special Turku Coronary Risk
      Factor Intervention Project for Babies (STRIP baby study), families of 540
      children were counseled to reduce exposure of children > 7 mo of age to known
      environmental risk factors for coronary heart disease. The control group
      consisted of 522 children whose families received no specific counseling
      concerning dietary fat. Iron and zinc intakes of 79 children aged 3-4 y (40 in
      the intervention group and 39 in the control group) were assessed with 4-d food
      records. The children in the intervention group consumed less saturated fat than
      those in the control group and had continuously higher ratios of dietary
      polyunsaturated to saturated fatty acids. Mean (+/- SD) daily iron intakes in the
      intervention and control groups were 8.8 +/- 4.2 mg and 8.6 +/- 2.8 mg,
      respectively. Laboratory findings in the intervention and control groups,
      respectively, were as follows: hemoglobin, 123 +/- 8 and 122 +/- 7 g/L; mean cell
      volume, 81.8 +/- 2.9 and 81.7 +/- 3.2 fL; mean corpuscular hemoglobin, 28.1 +/-
      1.3 and 27.8 +/- 1.4 pg; ferritin, 21.8 +/- 11.6 and 19.2 +/- 12.4 microg/L;
      transferrin, 2.90 +/- 0.30 and 2.85 +/- 0.29 g/L; and transferrin receptor, 2.34
      +/- 0.46 and 2.29 +/- 0.39 mg/L. There were no significant differences between
      the groups. Daily zinc intakes were 7.5 +/- 1.2 mg in the intervention group and
      7.4 +/- 1.3 mg in the control group; respective serum zinc concentrations were
      11.2 +/- 1.9 and 10.5 +/- 1.6 micromol/L (NS). In conclusion, long-term
      supervised use of a diet low in saturated fat and cholesterol did not influence
      intake or serum indicators of iron and zinc in children.

PMID- 9280176
TI  - Maternal energy balance and lactation performance of Mesoamerindians as a
      function of body mass index.
AB  - The effect of maternal energy balance in conjunction with body energy reserves on
      lactation performance has not been fully elucidated in humans. Energy balance was
      computed from changes in weight and body composition over 6 mo postpartum in 21
      Otomi Indian women with relatively low postpartum body mass indexes (BMIs; in
      kg/m2, 21.4 +/- 0.9) and 19 with relatively high BMIs (25.7 +/- 1.9). Body fat
      was determined by deuterium dilution. Milk production was estimated by 24-h test
      weighing. Macronutrient content of human milk was measured by standard
      techniques. In both groups weight declined over the 6 mo postpartum (P = 0.04).
      In the lower BMI group only, body fat (kg, % of wt) decreased significantly (P =
      0.04). Milk fat concentration was positively correlated with body fat at 3 and 6
      mo (r = 0.32 and 0.40; P = 0.04 and 0.01, respectively). Energy balance was not
      associated with milk production or composition, nutrient secretion into milk, or
      infant growth velocity, except at 6 mo, when energy balance was positively
      correlated with milk energy and fat concentration in the lower BMI group (r =
      0.55; P = 0.01). Fat concentration was lower in the lower BMI group (P = 0.04).
      Because of the inverse correlation between milk production and milk fat at 3 and
      6 mo (r = -0.47 and -0.43, respectively; P = 0.01), fat secretion into milk did
      not differ between groups. Infant growth velocities did not differ significantly
      between groups. In conclusion, negative energy balance in conjunction with lower
      energy reserves did not adversely affect lactation performance or infant growth
      in this population of Otomi Indians.

PMID- 9280177
TI  - Long-term effect of soluble-fiber foods on postprandial fat metabolism in
      dyslipidemic subjects with apo E3 and apo E4 genotypes.
AB  - To determine the long-term effect of soluble fiber on postprandial fat
      metabolism, we studied 33 dyslipidemic subjects, 16 with apolipoprotein (apo)
      E3/3 (E3) and 17 with E3/4 or E4/4 (E4) genotypes. They ate preweighed low-fat
      (20% of energy), high-fiber (> 5.7 g/MJ) diets for two 4-mo periods separated by
      a 2-mo washout period according to a randomized, crossover design. One diet
      contained foods rich in insoluble fiber and the other foods rich in soluble
      fiber. On 1 d during the last 2 wk of each diet, subjects ingested a standard,
      fiber-free, fatty liquid meal containing retinyl palmitate as a marker of
      intestinally derived lipoproteins. Plasma samples were obtained at hourly
      intervals for 10 h. Compared with the insoluble-fiber diet, soluble fiber reduced
      fasting plasma total cholesterol in both E3 (6.6 +/- 2.1%, P = 0.007)and E4
      subjects (5.6 +/- 2.1%, P = 0.017). Soluble fiber increased fecal total bile acid
      output in both E3 (76 +/- 18%, P < 0.001) and E4 subjects (85 +/- 19%, P <
      0.001). The incremental area under the chylomicron triacylglycerol response curve
      was significantly greater after soluble fiber than after insoluble fiber in E3
      (3.56 +/- 0.56 compared with 2.87 +/- 0.38 mmol x h/L, respectively, P = 0.046)
      but not in E4 subjects (5.19 +/- 0.78 compared with 4.92 +/- 0.81 mmol x h/L).
      Kinetic analysis suggested an increase in retinyl palmitate absorption in E3
      subjects after soluble fiber, but no difference in E4 subjects. These results
      suggest that a long-term increase in dietary soluble fiber has no effect on
      postprandial fat metabolism in subjects with an apo E3/4 or E4/4 genotype.
      However, soluble fiber enhances apparent fat absorption in E3 subjects, which
      could be due to an increased bile acid pool and increased micelle formation.

PMID- 9280178
TI  - Alpha-linolenic acid and marine long-chain n-3 fatty acids differ only slightly
      in their effects on hemostatic factors in healthy subjects.
AB  - The effects of alpha-linolenic acid (ALA, 18:3n-3), eicosapentaenoic acid (EPA,
      20:5n-3), and docosahexaenoic acid (DHA, 22:6n-3) on hemostatic factors were
      compared. Healthy subjects (29 women and 17 men aged 20-44 y) received either
      linseed oil (average ALA intake: 5.9 g/d) or fish oil plus sunflower oil (average
      EPA + DHA intake: 5.2 g/d) for 4 wk. The supplemented amount of fat was 1.19
      mg/kJ (1 g/200 kcal) calculated energy expenditure. Stability of habitual diets
      was monitored. Blood samples were collected at baseline, at the end of the
      experimental period, and after a 12-wk follow-up period. Different changes in the
      study groups were seen only in serum cholesterol and triacylglycerols, platelet
      fatty acid composition, and ADP-induced platelet aggregation. The treatments did
      not differ in their effects on collagen-induced platelet aggregation and
      thromboxane production, aggregation to the thromboxane A2 mimic I-BOP, urinary
      excretion of 11-dehydro-thromboxane B2 and beta-thromboglobulin, bleeding time,
      plasma fibrinogen concentration, antithrombin III activity, factor VII coagulant
      activity, or activity of plasminogen activator inhibitor 1. The results indicate
      that supplemented ALA from vegetable oil and EPA and DHA from a marine source
      have largely parallel effects on hemostatic factors.

PMID- 9280179
TI  - The effect of short-term fasting, apolipoprotein E gene polymorphism, and sex on
      plasma lipids.
AB  - The effect of 1 wk of supervised fasting on plasma lipid concentrations in
      subjects with different apolipoprotein E (apo E) phenotypes was studied in 58
      healthy free-living volunteers. The participants consumed an 870-kJ(208 kcal)/d
      liquid diet containing fruit and berry juices, tea, and water. The decline in
      plasma total cholesterol during 1 wk of fasting was 0.46 mmol/L in women and 0.35
      mmol/L in men. The decreases were significant in both women and men. The response
      patterns of plasma total cholesterol were not significantly different between the
      sexes. In men, the changes in plasma low-density-lipoprotein cholesterol during
      the fast differed significantly (P = 0.0181) between the apo E phenotypes,
      whereas in women there were no differences due to phenotype (P = 0.695). The
      magnitude of the change in plasma triacylglycerol during the fast was different
      between the sexes (P = 0.0099). The changes in plasma triacylglycerols differed
      significantly between apo E phenotype groups in men (P = 0.0295) but not in women
      (P = 0.0661). Statistical comparison between different apo E phenotypes was
      performed with and without the small apo E3,2+E2,2 group, with essentially
      similar results. During fasting, plasma high-density-lipoprotein cholesterol
      concentrations decreased slightly but not significantly. The study shows
      significant differences in the associations of apo E alleles and sex on plasma
      lipid responses during fasting and illustrates the importance of gene-diet
      interactions in the regulation of lipid metabolism in humans.

PMID- 9280180
TI  - Effect of haptoglobin on the metabolism of vitamin C.
AB  - Haptoglobin is a hemoglobin-binding antioxidant showing a genetic polymorphism
      with three types: Hp 1-1, Hp 2-1, and Hp 2-2. The Hp 2-2 type has been associated
      with an increased risk of atherosclerosis. We investigated vitamin C metabolism
      in vivo and in vitro according to haptoglobin type in a study group of 135
      healthy volunteers. Serum vitamin C concentrations were associated with
      haptoglobin type, showing lowest values in serum from Hp 2-2 subjects (P < 0.01).
      Renal threshold for L-ascorbic acid was within the normal range and
      metabolization to oxalate was not different among haptoglobin-type groups. Serum
      concentrations of other endogenous antioxidants (uric acid, bilirubin, albumin,
      ceruloplasmin, and total antioxidative status) were not different among
      haptoglobin-type groups. In vitro experiments showed a lower stability of L
      ascorbic acid in blood from subjects with the Hp 2-2 type (P < 0.01). L-Ascorbic
      acid depletion in vitro was inversely related to haptoglobin concentration (r = 
      0.738). The results of this study indicate a higher rate of L-ascorbic acid
      oxidation in Hp 2-2 carriers because they have less protection against hemoglobin
      iron driven peroxidation.

PMID- 9280181
TI  - Bone mineral and calcium accretion during puberty.
AB  - We measured bone mineral content (BMC) and estimated calcium accretion in
      children to provide insight into dietary calcium requirements during growth.
      Anthropometric measurements were done semiannually and whole-body BMC was
      measured annually by dual-energy X-ray absorptiometry for 4 y in 228 children
      (471 scans in 113 boys and 507 scans in 115 girls). Mean values for BMC, skeletal
      area, and height were calculated for 1-y age groups from 9.5 to 19.5 y of age.
      Cross-sectional analysis of the pooled data gave peak height velocity and peak
      BMC velocity (PBMCV) and the ages at which these occurred (13.3 y in boys and
      11.4 y in girls). PBMCV did not peak until 1.2 y after peak height velocity in
      boys and 1.6 y after peak height velocity in girls. Within 3 y on either side of
      PBMCV, boys had consistently higher BMC and BMC velocity compared with girls and
      the discrepancy increased steadily through puberty. Three years before PBMCV, BMC
      values in girls were 69% of those in boys; 3 y after peak height velocity this
      proportion fell to 51%. PBMCV was 320 g/y in boys and 240 g/y in girls. Under the
      assumption that bone mineral is 32.2% calcium, these values corresponded to a
      daily calcium retention of 282 mg in boys and 212 mg in girls. Individual values
      could be much greater. In one boy in a group of six subjects for whom there were
      enough data for individual analysis through puberty, PBMCV was 555 g Ca/y or 490
      mg Ca/d. Such high skeletal demands for calcium require large dietary calcium
      intakes and such requirements may not be met immediately in some children.

PMID- 9280182
TI  - Nickel metabolism in humans investigated with an oral stable isotope.
AB  - We report the results of the first complete study of nickel metabolism in human
      subjects using a stable nickel isotope (62Ni) as tracer. Four healthy adult
      subjects (two women and two men) fasted overnight before ingesting 10 microg
      62Ni/kg body wt. Blood samples were drawn after fixed intervals of time and the
      total daily output of urine and feces was collected for the first 5 d after dose
      ingestion. 62Ni in plasma, urine, and feces was determined by isotope-dilution
      inductively coupled plasma-mass spectrometry with 61Ni. The direct measurement of
      the fecal excretion of the tracer allowed a reliable assessment of nickel
      absorption from the gastrointestinal tract and we found no evidence of the
      excretion of absorbed nickel via the gut. The percentage absorption calculated
      from the amount of 62Ni excreted in the feces ranged from 29% to 40%. Urinary
      excretion over 5 d ranged from 51% to 82% of the absorbed dose. Plasma 62Ni
      peaked between 1.5 and 2.5 h after ingestion and decreased by a factor of > 10
      over the next few days. We observed low between-subject variability of nickel
      absorption and excretion. Confounding factors such as contamination and dietary
      intake of nickel, which hampered earlier measurements in subjects dosed with
      naturally abundant nickel, were eliminated by using the tracer isotope 62Ni.

PMID- 9280183
TI  - Prolonged fasting in humans results in diminished plasma choline concentrations
      but does not cause liver dysfunction.
AB  - Choline is a major donor of methyl groups, a precursor for membrane synthesis,
      and a component of the neurotransmitter acetylcholine. Choline-deficient diets
      deplete humans of choline and cause hepatic dysfunction and steatosis. In this
      study we determined whether acute starvation also depletes choline, as indicated
      by changes in plasma choline or phosphatidylcholine. Healthy humans (n = 10)
      fasted for 7 d, ingesting only water and mineral-vitamin supplements. Their mean
      (+/- SEM) plasma choline concentration was 9.5 +/- 0.5 micromol/L at the start of
      the study and dropped to 7.8 +/- 0.3 micromol/L after 1 wk of fasting (P < 0.01).
      The plasma phosphatidylcholine concentration did not change significantly (2.2 +/
      0.1 mmol/L at the start of the study and 2.4 +/- 0.2 mmol/L after 1 wk of
      fasting). Capacity of the liver to secrete lipoproteins was not affected by
      prolonged fasting. The mean plasma concentration of low-density-lipoprotein
      cholesterol was 3.3 +/- 0.2 mmol/L (126 +/- 8 mg/dL) at the start of the study
      and 4.9 +/- 0.5 mmol/L (188 +/- 19 mg/dL) after 1 wk of fasting. Liver damage
      assessed by serum alanine aminotransferase activity occurred in only 1 of 10
      subjects. We conclude that prolonged fasting in humans modestly diminished plasma
      choline but was not associated with signs of choline deficiency, such as
      perturbed lipoprotein secretion and liver damage.

PMID- 9280184
TI  - Measurement of retinoids and carotenoids in breast adipose tissue and a
      comparison of concentrations in breast cancer cases and control subjects.
AB  - A case-control study of the associations of retinoids and specific carotenoids
      with breast cancer using concentrations of these nutrients in breast adipose
      tissue was conducted among women attending a breast clinic in the Boston area in
      1989-1992. Breast adipose tissue was collected during breast biopsy. Cases (n =
      46) were women whose biopsies revealed invasive or in situ breast cancer; control
      subjects (n = 63) were women whose biopsies revealed benign disease. We observed
      inverse associations between breast adipose concentrations of retinoids and
      carotenoids and risk of breast cancer, although not all were statistically
      significant. The multivariate-adjusted odds ratio comparing women above the
      median value of the control group for retinol with those below or equal to the
      median was 0.71 (95% CI: 0.26, 1.93; NS); corresponding odds ratios were 0.61
      (95% CI: 0.23, 1.64; NS) for retinyl palmitate, 0.30 (95% CI: 0.11, 0.85) for
      beta-carotene, 0.32 (95% CI: 0.11, 0.94) for lycopene, and 0.68 (95% CI: 0.27,
      1.73; NS) for lutein/zeaxanthin. There was a nonsignificant positive correlation
      (r = 0.23, P = 0.15) between breast adipose tissue concentrations of retinol and
      dietary intake of preformed vitamin A, including supplements measured by using a
      food-frequency questionnaire. No correlation was found between breast adipose
      concentrations of carotenoids and intake of dietary carotenoids. These data
      suggest that higher breast adipose concentrations of retinoids and some
      carotenoids may be associated with decreased risk of breast cancer and that
      further examination of these relations is warranted.

PMID- 9280185
TI  - Lipolytic sensitivity to catecholamines in patients with human immunodeficiency
      virus infection.
AB  - Lipolysis is higher in patients with acquired immunodeficiency syndrome (AIDS)
      than in healthy control subjects. To evaluate whether this increase in lipolysis
      is related to increased beta-adrenergic sensitivity, we compared the lipolytic
      response to epinephrine (approximately 15 ng x kg(-1) x min(-1)) of six AIDS
      patients with that of six matched control subjects. Lipolysis was measured by
      infusion of [2H2]glycerol and [2H2]palmitate. The baseline rates of appearance of
      palmitate (2.06 +/- 0.21 compared with 1.45 +/- 0.07 micromol x kg(-1) x min(-1))
      and glycerol (2.35 +/- 0.16 compared with 1.35 +/- 0.06 micromol x kg(-1) x min(
      1)) were higher in AIDS patients (P < 0.05). The absolute increase in lipolysis,
      an indicator of the responsiveness to epinephrine, was not different between
      groups for the rate of appearance of palmitate (86 +/- 14 compared with 75 +/- 7
      micromol x L(-1) x min(-1)) or glycerol (79 +/- 13 compared with 59 +/- 6
      micromol x L(-1) x min(-1)). Plasma concentrations of epinephrine were not
      different between groups. Lipolysis was higher whereas the lipolytic response to
      epinephrine was normal in AIDS patients. Increased lipolytic sensitivity to
      catecholamines is not the cause of increased lipolysis in AIDS.

PMID- 9280186
TI  - Short-term zinc supplementation in women with non-insulin-dependent diabetes
      mellitus: effects on plasma 5'-nucleotidase activities, insulin-like growth
      factor I concentrations, and lipoprotein oxidation rates in vitro.
AB  - Non-insulin-dependent diabetes mellitus (NIDDM) may cause vulnerability to
      moderate zinc deficiency. In this study, short-term zinc supplementation (30 mg/d
      as amino acid chelate for 3 wk) elevated plasma zinc and activities of 5'
      nucleotidase, a zinc-dependant enzyme, in 20 postmenopausal women with NIDDM.
      Placebo, given to 20 other women with NIDDM, had no effects on these indexes nor
      on any others taken in this study. Although zinc supplementation doubled the mean
      value for 5'-nucleotidase activity, values were still significantly lower than
      those of age-matched control subjects. Plasma insulin-like growth factor I
      concentrations increased with zinc treatment if starting concentrations were <
      165 microg/L but were unchanged if they were > 165 microg/L. Lipoprotein
      oxidation in vitro, which has abnormal lag times and propagation rates for
      subjects with NIDDM and for moderately zinc-deficient rats, were unchanged by
      zinc supplementation. Possibly, this lack of effect occurred because the zinc
      treatment did not normalize zinc status. In conclusion, this study supports the
      contention that moderate zinc deficiency occurs frequently in subjects with
      NIDDM.

PMID- 9280187
TI  - Whole-body protein kinetics in children with kwashiorkor and infection: a
      comparison of egg white and milk as dietary sources of protein.
AB  - This study tested the hypothesis that during treatment of kwashiorkor (including
      marasmic kwashiorkor) with infection there is a lower rate of amino acid
      oxidation when the dietary intake of amino acids resembles the amino acid
      composition of acute phase proteins (APPs). Twenty-two children in Blantyre,
      Malawi, with kwashiorkor and acute infection were fed an isoenergetic,
      isonitrogenous diet with either egg white or milk as a protein source. The whole
      body amino acid oxidation rate was measured after 24 h by determining the plasma
      urea rate of appearance, and whole-body protein breakdown and synthesis rates
      were determined from the plasma leucine rate of appearance. Plasma concentrations
      of C-reactive protein, alpha1-antitrypsin, tumor necrosis factor alpha (TNF
      alpha), and interleukin 6 (IL-6) were determined on admission and at 24 and 48 h.
      The 11 children who received milk had a lower rate of amino acid oxidation than
      the children who received egg white (x +/- SD: 137 +/- 65 compared with 195 +/-
      66 micromol urea x kg body wt(-1) x h(-1), P < 0.05). No significant differences
      were found between the two groups in the rate of whole-body protein breakdown or
      protein synthesis. The TNF-alpha concentration correlated inversely with whole
      body protein breakdown and synthesis rates, and the IL-6 concentration correlated
      directly with C-reactive protein. We conclude that by making the amino acid
      composition of the diet resemble that of APPs in the treatment of acute
      kwashiorkor, the rate of amino acid oxidation can be decreased.

PMID- 9280188
TI  - Highly purified eicosapentaenoic acid and docosahexaenoic acid in humans have
      similar triacylglycerol-lowering effects but divergent effects on serum fatty
      acids.
AB  - To compare the effects of highly purified ethyl ester concentrates of
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on serum lipids,
      apolipoproteins, and serum phospholipid fatty acids in humans, we conducted a
      double-blind, placebo-controlled, parallel design intervention study. Healthy
      nonsmoking men (n = 234) aged 36-56 y were randomly assigned to dietary
      supplementation with 3.8 g EPA/d, 3.6 g DHA/d, or 4.0 g corn oil/d (placebo) for
      7 wk. Serum triacylglycerols decreased 26% (P < 0.0001) in the DHA group and 21%
      (P = 0.0001) in the EPA group compared with the corn oil group. Although not
      significant, net decreases in serum triacylglycerols were consistently greater in
      the DHA group across all quartiles of baseline triacylglycerol concentrations.
      Serum high-density-lipoprotein cholesterol increased 0.06 mmol/L (P = 0.0002) in
      the DHA group. In the EPA group, serum total cholesterol decreased 0.15 mmol/L (P
      = 0.02) and apolipoprotein A-I decreased 0.04 g/L (P = 0.0003). In the DHA group,
      serum phospholipid DHA increased by 69% and EPA increased by 29%, indicating
      retroconversion of DHA to EPA. In the EPA group, serum phospholipid EPA increased
      by 297% whereas DHA decreased by 15%, suggesting that EPA is not elongated to DHA
      in humans. The serum phospholipid ratio of n-3 to n-6 fatty acids increased in
      both groups, whereas the relative changes in n-6 fatty acids suggested possible
      alterations in liver desaturation activity in the DHA group. We conclude that
      both DHA and EPA decrease serum triacylglycerols, but have differential effects
      on lipoprotein and fatty acid metabolism in humans.

PMID- 9280189
TI  - Nutritional status and cardiac mass and function in children infected with the
      human immunodeficiency virus.
AB  - Malnutrition, skeletal muscle wasting, and changes in cardiac muscle mass and
      function have been described in children infected with the human immunodeficiency
      virus (HIV). This report analyzes the relation of nutritional status to cardiac
      muscle mass and function in HIV-infected children. Thirty-six children with
      symptomatic HIV infection underwent simultaneous anthropometric and
      echocardiographic evaluations before antiretroviral therapy or supplemental
      feedings. Nutritional measurements included weight, height, triceps skinfold
      thickness, and arm muscle circumference. Cardiac measurements included left
      ventricular mass, contractility, end-diastolic dimension, fractional shortening,
      blood pressure, and heart rate. In a cross-sectional analysis, children infected
      with HIV were significantly below age-adjusted standards for height (P = 0.0001),
      weight (P = 0.0001), triceps skinfold thickness (P = 0.001), and arm muscle
      circumference (P = 0.04). Left ventricular mass normalized to body surface area
      was below standard, but contractility was normal. Correlation analyses found an
      inverse relation between left ventricular mass and weight z score (r = -0.45, P =
      0.01), height z score (r = -0.47, P = 0.006), and arm muscle circumference
      percentile (r = -0.51, P = 0.003). An inverse relation was also found between
      heart rate and weight z score (r = -0.47, P = 0.007) and arm muscle circumference
      percentile (r = -0.46, P = 0.007). In malnourished children with HIV infection, a
      paradoxical relation exists between nutritional status and cardiac muscle mass.
      The inverse relation between heart rate and nutritional status may suggest
      altered metabolic rates with possible increased sympathetic tone.

PMID- 9280190
TI  - Serum retinol concentrations and Schistosoma mansoni, intestinal helminths, and
      malarial parasitemia: a cross-sectional study in Kenyan preschool and primary
      school children.
AB  - Parasitic determinants of serum retinol concentrations were studied in 159
      preschool (0.25-5.1 y) and 695 primary school (9.2-17 y) children in western
      Kenya. Mean serum retinol was 0.63 micromol/L in preschool and 0.94 micromol/L in
      primary school children; 62% and 24%, respectively, had serum retinol < 0.70
      micromol/L. Serum retinol was lower in boys than in girls among both preschool (P
      = 0.04) and primary school children (P = 0.0001). Schistosoma mansoni, Ascaris
      lumbricoides, hookworm, and Trichuris trichiura egg output and malarial
      parasitemia were determined and their relation with serum retinol assessed. Among
      preschool children, sex, elevated serum concentrations of C-reactive protein, and
      malarial parasitemia were significant predictors of serum retinol. Among the 63
      children from whom stool samples were available, none of the helminth infections
      were significant predictors of serum retinol. For primary school children, age,
      sex, and S. mansoni egg output were predictors of serum retinol. Malarial
      parasitemia among nonimmune preschool children may contribute to low serum
      retinol, whereas malarial parasitemia did not have any effects in semiimmune
      primary school children. In contrast, the inverse relation between S. mansoni and
      serum retinol found in primary school children could be due to an effect of
      infection on serum retinol or an increased susceptibility to infection among
      children with low serum retinol. Although parasitic infections may contribute to
      poor vitamin A status in children, they do not explain the age and sex
      differences.

PMID- 9280191
TI  - Are genetic determinants of weight gain modified by leisure-time physical
      activity? A prospective study of Finnish twins.
AB  - A large number of studies have shown that obesity is both under genetic control
      and influenced by several environmental factors, including energy expenditure and
      intake. Several studies in animals and humans have furthermore suggested that
      certain environmental factors, such as a high fat intake, may modify the
      expression of the genes responsible for weight gain. The present study examined
      whether physical activity, measured at the baseline examination in 1975, was
      likely to play a differential role in subsequent weight changes in the following
      6 y in 1571 monozygotic and 3029 dizygotic, same-sex twin pairs from the Finnish
      Twin Cohort Study. A hierarchical multiple-regression analysis was used to test
      for gene-environment interactions by identifying significant three-way
      interactions between genetic factors, physical activity, and weight change. The
      results showed that associations between weight change in twin A and twin B were
      significantly stronger for monozygotic than for same-sex dizygotic twins at all
      levels of physical activity. Additionally, in the monozygotic men the strength of
      the association varied with physical activity level, and the association between
      the change in body mass index between the twin pairs with the highest physical
      activity level was about three times stronger (beta = 0.40) than the association
      in twin pairs with the lowest physical activity level (beta = 0.15, P for trend =
      0.002). In pairs of dizygotic men, and in both monozygotic and dizygotic women,
      similarity in body mass index change was independent of physical activity level
      (all P > 0.14). The present study showed that genetic factors may modify the
      effects of physical activity on weight change, and suggests that a sedentary
      lifestyle may have an obesity-promoting effect in men with a genetic
      predisposition.

PMID- 9280192
TI  - Hypoenergetic nutrition support in hospitalized obese patients.

PMID- 9280193
TI  - Is zinc nutriture a problem in persons with diabetes mellitus?

PMID- 9280194
TI  - Nutrition support in clinical practice: review of published data and
      recommendations for future research directions. Summary of a conference sponsored
      by the National Institutes of Health, American Society for Parenteral and Enteral
      Nutrition, and American Society for Clinical Nutrition.
AB  - In the last 30 years, marked advances in enteral feeding techniques, venous
      access, and enteral and parenteral nutrient formulations have made it possible to
      provide nutrition support to almost all patients. Despite the abundant medical
      literature and widespread use of nutritional therapy, many areas of nutrition
      support remain controversial. Therefore, the leadership at the National
      Institutes of Health, The American Society for Parenteral and Enteral Nutrition,
      and The American Society for Clinical Nutrition convened an advisory committee to
      perform a critical review of the current medical literature evaluating the
      clinical use of nutrition support; the goal was to assess our current body of
      knowledge and to identify the issues that deserve further investigation. The
      panel was divided into five groups to evaluate the following areas: nutrition
      assessment, nutrition support in patients with gastrointestinal diseases,
      nutrition support in wasting diseases, nutrition support in critically ill
      patients, and perioperative nutrition support. The findings from each group are
      summarized in this report. This document is not meant to establish practice
      guidelines for nutrition support. The use of nutritional therapy requires a
      careful integration of data from pertinent clinical trials, clinical expertise in
      the illness or injury being treated, clinical expertise in nutritional therapy,
      and input from the patient and his/her family. (Journal of Parenteral and Enteral
      Nutrition 21:133-156, 1997).

PMID- 9280195
TI  - Helicobacter pylori and vitamin A status in children.

PMID- 9280196
TI  - Vitamin E supplementation and plasma ascorbate.

PMID- 9280197
TI  - Fatty acid chain-length designations are important to study conclusions.

PMID- 9280198
TI  - Why are large legs protective?

PMID- 9280199
TI  - trans Fatty acids: infant and fetal development.
AB  - This review evaluates scientific data associated with the possibility that trans
      fatty acids compromise fetal and infant early development. Concerns have been
      triggered by research that has heightened our awareness of the importance of n-3
      and n-6 fatty acids; shown that trans fatty acids inhibit delta6 desaturation of
      linoleic acid; identified trans fatty acid isomers in fetal, infant, and maternal
      tissues; and reported an inverse association between the trans fatty acid content
      of tissue lipids and measures of growth and development. Animal studies provide
      little evidence that trans fatty acids influence growth, reproduction, or gross
      aspects of fetal development. However, these models may not have been appropriate
      for addressing all the subtle effects that influence development of human infant
      retinal, neural, or brain function. Human studies are hampered by the complexity
      of the interrelations among nutritional, genetic, and environmental factors and
      by ethical considerations that constrain the research design. Existing data have
      not established a causal relation between trans fatty acid intake and early
      development. Conclusions cannot be drawn from the possible association found
      between trans fatty acid exposure and lower n-3 and n-6 long-chain
      polyunsaturated fatty acids and growth because of confounding factors. Few
      studies addressed the question of whether trans fatty acids adversely affect
      human fetal growth. One study reported a correlation between the trans fatty acid
      content of plasma and birth weight of preterm infants and one study reported a
      relation between preterm births and the trans fatty acid content of maternal
      plasma. Limited associative data have addressed whether trans fatty acids
      adversely affect fetal and infant neurodevelopment and growth. The interpretation
      of existing research and development of recommendations should be done
      cautiously. Suggestions for research to clarify these issues are made.

PMID- 9280200
TI  - A welcome debate on how to measure the left ventricular mass.

PMID- 9280202
TI  - Calculation of left ventricular mass in man--a comment.

PMID- 9280201
TI  - Measurement of left ventricular mass: methodology and expertise.
AB  - The strong relation between increased left ventricular mass and cardiovascular
      events makes accurate measurement of left ventricular mass a high priority,
      especially in patients with hypertension. M-mode echocardiography is used most
      widely to measure left ventricular mass because of its wide availability,
      moderate expense, anatomic and prognostic validation and lack of radiation or
      claustrophobia; however, this technique is expertise-dependent and may give
      erroneous results in distorted ventricles. Two-dimensional and especially three
      dimensional echocardiography increase the precision with which left ventricular
      mass is measured but they are more time-consuming and difficult to perform on a
      large scale. Magnetic resonance imaging provides highly accurate left ventricular
      mass measurements and permits tissue imaging but its use is limited by expensive,
      fixed facilities and claustrophobia. Cine computed X-ray tomography also measures
      left ventricular mass accurately and permits perfusion assessment with contrast
      injection but it involves radiation and the use of fixed facilities of limited
      availability. Understanding the strengths and limitations of available techniques
      can facilitate selection of the most appropriate method to measure left
      ventricular mass in a particular setting.

PMID- 9280203
TI  - Atrial natriuretic peptide-C receptor and membrane signalling in hypertension.
AB  - Atrial natriuretic peptide (ANP) regulates a variety of physiological parameters,
      including the blood pressure and intravascular volume, by interacting with its
      receptors present on the plasma membrane. ANP receptors are of three subtypes:
      ANP-A, -B and -C receptors. ANP-A and ANP-B receptors are guanylyl cyclase
      receptors, whereas ANP-C receptors are coupled to adenylyl cyclase inhibition or
      phospholipase C activation through inhibitory guanine nucleotide-regulating
      protein. Unlike other G protein-coupled receptors, ANP-C receptors have a single
      transmembrane domain and a short cytoplasmic domain of 37 amino acids, the
      cytoplasmic domain has a structural specificity like those of other single
      transmembrane-domain receptors and 37 amino-acid cytoplasmic domain peptide is
      able to exert is inhibitory effect on adenylyl cyclase. The activation of ANP-C
      receptor by C-ANP(4-23) (a ring-deleted peptide of ANP) and C-type natriuretic
      peptide inhibits the mitogen-activated protein kinase activity stimulated by
      endothelin-3, platelet-derived growth factor and phorbol-12 myristate 13-acetate.
      C-ANP also inhibits mitogen-induced stimulation of DNA synthesis, indicating that
      the ANP-C receptor plays a role in cell proliferation through an inhibition of
      mitogen-activated protein kinase and suggesting that the ANP-C receptor might
      also be coupled to other signal transduction mechanism(s) or that there might be
      an interaction of the ANP-C receptor with some other signalling pathways. ANP
      receptor binding is decreased in most organs in hypertensive subjects and
      hypertensive animals. This decrease is consistent with there being fewer guanylyl
      cyclase-coupled receptors in the kidney and vasculature and selective inhibition
      of the ANP-C receptor in the thymus and spleen. Platelet ANP-C receptors are
      decreased in number in hypertensive patients and spontaneously hypertensive rats.
      ANP-A, -B and -C receptors are decreased in number in deoxycorticosterone acetate
      salt-treated kidneys and vasculature; however, the responsiveness of adenylyl
      cyclase to ANP is augmented in the vasculature and heart and is attenuated
      completely in platelets. These alterations in ANP receptor subtypes may be
      related to the pathophysiology of hypertension. Several hormones such as
      angiotensin II, ANP and catecholamines, the levels of which are increased in
      hypertension, downregulate or upregulate ANP-C receptors and ANP-C receptor
      mediated inhibition of adenylyl cyclase. It can be suggested that the
      antihypertensive action of several types of drugs such as angiotensin converting
      enzyme inhibitors, angiotensin type 1 receptor antagonists and beta2-adrenergic
      antagonists may partly be attributed to their ability to modulate the expression
      and function of the ANP-C receptor.

PMID- 9280204
TI  - Factors affecting the nocturnal decrease in blood pressure: a community-based
      study in Ohasama.
AB  - OBJECTIVE: To investigate factors affecting the nocturnal decrease in blood
      pressure. DESIGN: A cross-sectional study of 823 community-based untreated
      subjects aged > 20 years. Screening and ambulatory blood pressures were measured
      and the effects of age and the ambulatory blood pressure on the nocturnal
      decrease were examined. RESULTS: The magnitude of the decrease and the percentage
      decrease in the nocturnal blood pressure increased with increasing daytime
      ambulatory blood pressure and decreased with increasing night-time ambulatory
      blood pressure. Although the magnitude of the nocturnal decrease in blood
      pressure increased with increasing daytime blood pressure, the nocturnal blood
      pressure levels in hypertensives were still higher than those in normotensive
      subjects. The magnitude decreased with increasing age for men but not for women,
      whereas the percentage decrease decreased with increasing age both for men and
      for women. The SD of the 24 h blood pressure correlated strongly to the magnitude
      of the nocturnal decrease (systolic blood pressure r = 0.62, P < 0.0001;
      diastolic blood pressure r = 0.52, P < 0.0001), suggesting that the SD of the 24
      h blood pressure is representative of the nocturnal decrease. A minimal nocturnal
      decrease was observed frequently in elderly normotensive men but infrequently in
      hypertensive individuals from the general population. A marked nocturnal decrease
      was observed frequently in hypertensive women aged > 70 years. CONCLUSION:
      Although the magnitude of the nocturnal decrease in blood pressure increased with
      increasing daytime blood pressure, the nocturnal blood pressure levels increased
      with increasing daytime ambulatory blood pressure. Therefore, the blood pressure
      in hypertensive subjects should essentially be lowered throughout the 24 h
      period. A marked nocturnal decrease in blood pressure in some elderly
      hypertensive women was observed without treatment. The nocturnal blood pressure
      levels of such subjects should be considered during treatment.

PMID- 9280205
TI  - Psychophysiological reactivity of salt-sensitive normotensive subjects.
AB  - OBJECTIVE: To evaluate the psychophysiological response to mental stress of young
      healthy salt-sensitive normotensive subjects. METHODS: Thirty-two healthy
      volunteers who had previously been phenotyped for salt sensitivity were selected
      for the study. The 16 salt-sensitive and 16 salt-resistant subjects, who were
      matched for age, body mass index and family history of hypertension, underwent a
      mental stress test consisting of an information-processing task performed under
      time pressure (the Manometer test). During the experimental session the blood
      pressure, heart rate and pulse-wave velocity were registered continuously. Before
      and after the mental task subjects were instructed to complete several
      standardized psychological state and trait questionnaires. RESULTS: Mental stress
      resulted in a greater rise in blood pressure (P < 0.05) and in pulse-wave
      velocity (P < 0.01) in salt-sensitive than in salt-resistant individuals. Salt
      sensitive subjects also displayed significantly higher levels of anxiety (P <
      0.01) and a lower level of control of anger (P < 0.01) than did salt-resistant
      subjects. Furthermore, the level of irritation of the salt-sensitive subjects was
      higher both before (P < 0.01) and after (P < 0.05) the stress test CONCLUSIONS:
      An increased responsiveness of the blood pressure to mental stress and an
      increased level of irritation are associated with salt sensitivity in
      normotensive subjects. These findings are in line with the hypothesis that
      psychophysiological traits play a role in the development of salt-sensitive
      hypertension.

PMID- 9280206
TI  - Relationship between ambulatory and resting blood pressure responses to dietary
      salt restriction in normotensive men.
AB  - OBJECTIVE: To examine the relationship between changes in resting and ambulatory
      blood pressures induced by dietary salt restriction in 90 young normotensive men.
      METHODS: Subjects were given a standardized low-salt diet containing 20 mmol
      sodium chloride per day for 14 days. To this diet, a daily supplement of 20
      tablets of slow sodium (10 mmol NaCl per tablet) or placebo was added in a
      randomized single-blind cross-over fashion for 7 days. The ambulatory blood
      pressure was measured on the sixth day and the resting blood pressure was
      measured on the seventh day of each dietary period. RESULTS: Although salt intake
      did not affect blood pressure levels in the whole group, the response of the
      blood pressure was quite variable among individual subjects. Salt-induced changes
      in resting systolic (r = 0.30, P = 0.006) and mean (r = 0.27, P = 0.014) blood
      pressures, but not diastolic blood pressure, were correlated positively to
      changes in daytime ambulatory blood pressure. The changes in resting systolic and
      mean blood pressures were also correlated significantly to the nocturnal falls in
      systolic (r = 0.26, P = 0.015) and mean (r = 0.27, P = 0.012) blood pressure
      levels and heart rate (r = 0.26, P= 0.015) under the high-salt diet. Diet-induced
      changes in resting mean blood pressure were correlated significantly to the
      daytime ambulatory blood pressure (r = 0.30, P < 0.005) and the resting heart
      rate (r = 0.24, P < 0.02) under the high-salt diet. CONCLUSION: Salt-induced
      changes in resting blood pressure in young normotensive men are correlated
      positively to changes in ambulatory daytime blood pressure levels as well as to
      the daytime ambulatory blood pressure and the nocturnal fall in blood pressure
      under a high-salt diet. These findings suggest that dietary salt-intake
      restriction can lower both resting and daytime ambulatory blood pressure levels
      in some normotensive individuals who may be predisposed to the development of
      hypertension.

PMID- 9280207
TI  - Effect of a chronic high-salt diet on whole-body and organ sodium contents of
      Dahl rats.
AB  - OBJECTIVE: To evaluate whether a high-salt diet causes retention of Na in Dahl
      rats. DESIGN: To compare the whole-body and organ (liver, spleen, kidney, heart,
      lung, femur, submaxillary gland and muscle) Na contents in Dahl salt-sensitive
      rats and Dahl salt-resistant rats. METHODS: Rats aged 6-10 weeks of both strains
      were fed a normal-salt (0.4% NaCl) or a high-salt (8% NaCl) diet. The whole-body
      and organs were then ashed and their respective Na contents determined. RESULTS:
      Salt-resistant rats fed the normal-salt diet had a higher whole-body Na content
      than did salt-sensitive rats. The high-salt diet increased the whole-body Na
      content of salt-sensitive rats significantly, but it did not increase that of
      salt-resistant rats. The high-salt diet caused a significant increase in the
      organ weight: body weight ratio for all organs of the salt-sensitive rats, except
      the submaxillary gland, but had no effect on the ratios for salt-resistant rats,
      apart from that for the kidney. The kidney, submaxillary gland and muscle Na
      concentrations were greater in salt-sensitive rats than they were in salt
      resistant rats. Nonetheless, regardless of strain, the high-salt diet had no
      effect on organ and plasma Na concentrations. The high-salt diet increased the
      organ weights (liver, spleen, kidney, heart and lung) and the organ Na contents
      per kg body weight significantly for salt-sensitive rats but not for salt
      resistant rats. CONCLUSIONS: A high-salt diet caused Na retention in salt
      sensitive rats only and this was partially due to enlargement of the organs.

PMID- 9280208
TI  - Elevated blood pressure in spontaneously hypertensive rats consuming a high
      sucrose diet is associated with elevated angiotensin II and is reversed by
      vanadium.
AB  - OBJECTIVE: To determine the changes in serum angiotensin II (Ang II) and
      endothelin-1 levels induced by vanadium treatment of sugar-fed rats in order to
      investigate the relationship between changes in blood pressure and Ang II and
      endothelin-1 levels. METHODS: Male spontaneously hypertensive rats (SHR) were fed
      starch (control), sucrose, and sucrose plus vanadium compounds at various
      concentrations. The systolic blood pressure of the rats was estimated by tail
      cuff plethysmography. Serum Ang II and endothelin-1 levels were measured by
      radioimmunoassay. RESULTS: There were increases in systolic blood pressure (by
      8%) and in serum Ang II (by 20%) in sucrose-fed SHR compared with control. In
      sucrose plus vanadium-fed SHR, the lowering of the systolic blood pressure (by 11
      16% of the sucrose-fed value) was accompanied by a significant decrease in Ang II
      levels (by 25-60% of the sucrose-fed value) and an increase in endothelin-1 level
      (by 61-76% of the sucrose-fed value). CONCLUSION: That Ang II levels are elevated
      in sucrose-induced hypertension and decreased after vanadium therapy suggests
      that the renin-angiotensin system plays a role in the induction of hypertension
      in this model. On the other hand, the elevation of endothelin-1 levels associated
      with a decreased systolic blood pressure might be secondary to vanadium
      stimulation of endothelial cells. The data suggest that endothelin-1 is not
      involved in sugar-induced elevations of the blood pressure.

PMID- 9280209
TI  - Liver microsomal membrane fluidity and microsomal desaturase activities in adult
      spontaneously hypertensive rats.
AB  - OBJECTIVE: The purpose of the present study was to investigate liver microsomal
      membrane fluidity simultaneously with membrane fatty acid composition and
      desaturase activities in spontaneously hypertensive rats (SHR). DESIGN AND
      METHODS: The membrane fluidity was determined, after electron spin resonance
      (ESR) measurement, in SHR compared with normotensive Wistar-Kyoto (WKY) rats, by
      calculating the order parameter S from ESR spectra of 5-nitroxide stearate and 10
      nitroxide stearate, used as spin-labelled fatty acids. Desaturase activities were
      measured by incubating SHR and WKY rat liver microsomes with [14C]-radiolabeled
      fatty acids as substrates for desaturation reactions. The fatty acid composition
      of liver microsomal membranes was determined by gas-liquid chromatography.
      RESULTS: Whereas no significant difference between S of 5-nitroxide stearate was
      observed for SHR and WKY rats, S of 10-nitroxide stearate was significantly lower
      in SHR than it was in WKY rat microsomal membrane, indicating that the core
      microsomal membrane fluidity was higher in SHR. Significant differences between
      fatty acid compositions were observed for SHR and WKY rat microsomal membranes.
      Delta9 and n-6 delta6 microsomal desaturase activities were significantly lower
      in SHR. CONCLUSION: These results suggest that the higher liver core microsomal
      membrane fluidity observed in SHR might be dependent on the increased proportion
      of mono-unsaturated fatty acids. Such observed modifications and the alterations
      in delta9 and n-6 delta6 desaturase activities suggest that an impaired
      polyunsaturated fatty acid biosynthesis is related to changes in microsomal
      membrane fluidity in hypertension.

PMID- 9280210
TI  - Cytosolic calcium changes induced by angiotensin II in human peripheral blood
      mononuclear cells are mediated via angiotensin II subtype 1 receptors.
AB  - OBJECTIVE: To determine the effects of angiotensin II (AII) (1-8) on cytosolic
      free calcium concentrations in the absence and in the presence of the selective
      angiotensin subtype 1 (AT1) receptor antagonist losartan and of the selective
      angiotensin subtype 2-receptor antagonist P-186 in human peripheral blood
      mononuclear cells (PBMC). We also assessed the effect of the AII analogues AII (2
      8), AII (3-8) and AII (4-8) on the cytosolic free-calcium concentration in human
      PBMC. METHODS: The cytosolic free-calcium concentration was assayed in human
      peripheral blood mononuclear cells by measuring the fluorescence of fura-2
      entrapped by these cells. RESULTS: Administration of AII caused a concentration
      dependent increase in the cytosolic free-calcium concentration in human
      peripheral blood mononuclear cells with a half-maximal increase at 5 x 10(-8)
      mol/l. Also administration of the heptapeptide AII (2-8) increased the
      intracellular free-calcium concentration in human PBMC, whereas AII (3-8) and AII
      (4-8) had no effect. The AII (1-8)-induced rise in cytosolic free-calcium
      concentration was blocked completely by losartan but not by P-186. CONCLUSION:
      Our data demonstrate that the effects of AII on the cytosolic free-calcium
      concentration in human PBMC are AT1 receptor-mediated since they were abolished
      by the specific AII AT1 receptor antagonist losartan but not by the specific
      angiotensin subtype 2 receptor antagonist P-186.

PMID- 9280211
TI  - Effect of administered potassium on the renin-aldosterone axis in young blacks
      compared with whites.
AB  - BACKGROUND: We had observed previously that the aldosterone excretion rate and
      plasma aldosterone concentration were lower for black children than they were for
      white children. We did not know whether this was secondary to a lower intake of
      potassium or to suppression of the renin-angiotensin system in blacks. OBJECTIVE:
      To test the hypothesis that the secretion of aldosterone in response to potassium
      would be different in blacks than in a control group of whites. DESIGN: Black and
      white subjects were selected on the basis of their having aldosterone excretion
      rates that were in the lowest quartile for the entire original cohort. Since the
      blacks typically had lower aldosterone excretion rates than did the whites, the
      black participants were represented primarily by those with average rates of
      aldosterone production among blacks, whereas the whites were represented by those
      with the lowest aldosterone production rates among whites. The protocol consisted
      of a placebo-controlled, randomized cross-over study design. METHODS: Twelve
      blacks and 12 whites, aged 14.1 +/- 1.6 (mean +/- SD) and 15.4 +/- 2.1 years,
      respectively, were allocated randomly to double-blind treatment either with
      placebo or with 40 mmol/day potassium chloride for 7 days and then the alternate
      treatment Measurements of the plasma renin activity (PRA), plasma aldosterone
      concentration, and urinary aldosterone excretion were performed in an inpatient
      research unit at the end of the treatment. The blood pressure was monitored for
      24 h. RESULTS: Treatment with potassium increased the plasma aldosterone
      concentration (P = 0.0006) and the urinary excretion of aldosterone (P = 0.0002)
      significantly both for blacks and for whites. There was no significant racial
      difference in the response to potassium. The PRA was overall 1.605-fold lower in
      the blacks than it was in the whites (P = 0.0124). The lowest PRA levels, such as
      those in the blacks when they were supine, tended to be increased with the
      potassium treatment. The blood pressure did not change significantly with the
      potassium supplement for either racial group. CONCLUSIONS: After we had
      supplemented the intake of potassium, aldosterone production increased in the
      blacks and in the control group of whites to the same extent The potassium
      treatment appeared to increase lower PRA levels. A lower intake of potassium
      could at least partially account for the suppression of the renin-aldosterone
      system in blacks.

PMID- 9280212
TI  - Circulating angiotensin converting enzyme levels are increased in concentric, but
      not eccentric, left ventricular hypertrophy in elderly men.
AB  - OBJECTIVE: To study the cross-sectional relationship between circulating
      angiotensin converting enzyme (ACE) activity and echocardiographically determined
      left ventricular geometry in a study of 380 70-year-old men participating in a
      health-survey reexamination and 50 patients with hypertension. METHODS: Two
      dimensional guided M-mode and Doppler echocardiography. Fluorometric assay of
      serum ACE activity. RESULTS: The serum ACE activity was higher in the elderly men
      with left ventricular concentric hypertrophy than it was in men with normal
      geometry and left ventricular eccentric hypertrophy (32, 27, and 26 U/l,
      respectively, P < 0.01 for both comparisons before and after adjustment for the
      24 h mean arterial pressure, body mass index, and use of antihypertensive
      medication). The serum ACE activity correlated with the thickness of the left
      ventricular interventricular septum (r = 0.12, P = 0.0095), the left ventricular
      relative wall thickness (r = 0.13, P = 0.0053 ), and the total peripheral
      resistance (r = 0.16, P = 0.0034), but not with the left ventricular mass (r = 
      0.039, P = 0.45) of these elderly men. The serum ACE activity in the hypertensive
      patients also correlated with the left ventricular interventricular septum
      thickness (r = 0.34, P = 0.020) independently of the 24 h mean arterial blood
      pressure, age, sex, body mass index, and insulin sensitivity. CONCLUSION: Levels
      of serum ACE activity are associated with left ventricular geometry.

PMID- 9280213
TI  - Angiotensin II induces activation of phosphatidylinositol 3-kinase in
      cardiomyocytes.
AB  - BACKGROUND: Phosphatidylinositol 3-kinase phosphorylates membrane lipids at the
      third position of the inositol ring producing phosphoinositides, not on the
      pathway for production of 1,4,5-triphosphate. OBJECTIVE: To test the hypotheses
      that angiotensin II (Ang II) activates phosphatidylinositol 3-kinase in
      cardiomyocytes and that this pathway is involved in Ang II-induced protein
      synthesis. METHODS: Cardiomyocytes, in culture, from 7-day-old chick embryonic
      hearts were treated with Ang II and the activation of phosphatidylinositol 3
      kinase was assessed after immunoprecipitation with antibodies to the p85 subunit
      of phosphatidylinositol 3-kinase by the conversion of PI (phosphatidylinositol)
      to phosphatidylinositol 3-monophosphate (PIP) in the presence of gamma-[32P]-ATP
      and analyzed by thin-layer chromatography. Western blotting was performed after
      antiphosphotyrosine immunoprecipitation with antibodies to the p85 subunit of
      phosphatidylinositol 3-kinase. Protein synthesis was assessed by [35S]-methionine
      incorporation and polyacrylamide gel electrophoresis. RESULTS: Ang II stimulated
      phosphatidylinositol 3-kinase activity dramatically, with 4.5- and 3.5-fold
      increases in PIP formation after 1 and 5 min, respectively. The involvement of
      tyrosine kinases was demonstrated by Western blotting in which Ang II increased
      tyrosine phosphorylation of a protein recognized by antibodies to the 85 kDa
      subunit of phosphatidylinositol 3-kinase. Furthermore, the tyrosine kinase
      inhibitor lavendustin A blocked Ang II-stimulated phosphatidylinositol 3-kinase
      activity and conversion of phosphatidylinositol to PIP. Ang II increased new
      protein synthesis as reflected by the significantly (P < 0.05) greater
      incorporation of [35S]-methionine into cardiomyocytes treated with Ang II. The
      link between Ang II and protein synthesis was mediated in part through
      phosphatidylinositol 3-kinase because the phosphatidylinositol 3-kinase inhibitor
      wortmannin blocked the effect of Ang II on protein synthesis. Increased
      production both of nuclear and of cytosolic proteins was demonstrated by agarose
      gel electrophoresis of these cellular components of Ang II-treated
      cardiomyocytes. Wortmannin produced a general inhibition of the synthesis of
      nuclear and cytosolic proteins, with a greater effect on nuclear proteins. The
      action of wortmannin on nuclear protein synthesis was confirmed by similar
      findings with another phosphatidylinositol 3-kinase inhibitor, LY294002.
      CONCLUSION: Phosphatidylinositol 3-kinase activation by Ang II occurs through a
      pathway utilizing tyrosine phosphorylation. Furthermore, this pathway is involved
      in cardiomyocyte protein synthesis and the possibility that it is operative in
      Ang II-mediated cardiac hypertrophy arises.

PMID- 9280214
TI  - Nitric oxide synthase inhibitors and hypertension in children and adolescents.
AB  - OBJECTIVE: To establish the role played by the circulating nitric oxide synthase
      inhibitors N(G)-monomethyl-L-arginine (L-NMMA), asymmetrical dimethyl arginine
      (ADMA) and symmetric dimethyl arginine (SDMA) and its association with
      hypertension of children and adolescents. DESIGN: We measured plasma
      concentrations of L-NMMA, ADMA and SDMA in 38 hypertensives (median age 7.7
      years) and in nine healthy normotensive controls (median age 8.2 years) using
      high-performance liquid chromatography. In addition, their plasma renin activity
      was determined. The subjects' glomerular filtration rates were calculated from
      plasma creatinine and height measurements. To determine the vasoactive potency of
      the arginine analogues, concentration-response curves were plotted for the
      responses in isolated endothelium-intact and endothelium-denuded mouse aortic
      rings that had been pre-contracted by administration of a threshold concentration
      of phenylephrine. RESULTS: Plasma ADMA and SDMA concentrations in members of the
      hypertensive group [0.23 +/- 0.03 and 1.37 +/- 0.06 micromol/l, respectively
      (means +/- SEM)] were significantly higher than those in members of the control
      group (ADMA 0.10 +/- 0.01 micromol/l and SDMA 1.18 +/- 0.06 micromol/l). Plasma
      concentrations of L-NMMA were similar in members of the hypertensive (0.21 +/-
      0.01 micromol/l) and control (0.18 +/- 0.02 micromol/l) groups. The glomerular
      filtration rate of the hypertensive group was below normal [70.4 +/- 5.4 ml/min
      per 1.73 m2 (mean +/- SEM)] and was significantly associated with elevated plasma
      concentrations of ADMA (r = -0.77, P < 0.001), SDMA (r = -0.38, P = 0.02) and L
      NMMA (r = 0.35, P = 0.03). Higher plasma ADMA concentrations were associated with
      a lower plasma renin activity (r = -0.36, P = 0.04). The vasoactive potencies of
      ADMA (concentration for half-maximal effect with the endothelium intact 25.4 +/-
      7.1 micromol/l) and L-NMMA (concentration for half-maximal effect with the
      endothelium intact 8.2 +/- 2.9 micromol/l) was significantly (P < 0.05) greater
      than that of SDMA. Both ADMA and L-NMMA (at 3 micromol/l concentrations)
      initiated a significant vasocontractile response from baseline (P = 0.03 and P <
      0.001, respectively). These effects were absent after the endothelium had been
      removed. SDMA had no effect. CONCLUSIONS: Plasma ADMA and SDMA levels are
      increased in hypertensive children. By inference from in-vitro data, ADMA appears
      to attain sufficient concentrations to produce a significant change in vascular
      tone and hence might play a role in the pathophysiology of childhood
      hypertension.

PMID- 9280215
TI  - Differential effects of vasopressin and endothelium-1 on vascular contractile and
      calcium responses in pressurized small arteries from spontaneously hypertensive
      rats.

PMID- 9280216
TI  - Does high-dose chemotherapy have a defined role in the treatment of solid tumors
      in 1997?

PMID- 9280218
TI  - The biology of lung cancer.
AB  - Lung cancer is the most common cause of cancer death in the United States among
      both men and women, with an estimated 177,000 new cases and 159,000 deaths in
      1996. Its overall incidence is increasing, particularly in women, and despite
      many complex and aggressive approaches to therapy, and great strides in
      understanding its biology and etiology, corresponding improvements in outcome are
      not yet apparent. This article will summarize the state of knowledge of the
      biology and genetics of lung cancer. These and future advances in our knowledge
      will certainly provide the foundation for future advances in therapeutics.

PMID- 9280220
TI  - Imaging of lung cancer: old and new.
AB  - Lung cancer is the leading cause of cancer death in the United States. Lung
      cancer is frequently encountered by the radiologist, whether the lung cancer is
      detected on a chest radiograph obtained in a symptomatic patient, or is an
      incidental finding. The radiologic workup of pulmonary lesions suspected of being
      lung carcinoma has evolved as new technology has become available. Current
      imaging modalities which are useful in the workup of suspected lung cancers
      include plain radiography, computed tomography, magnetic resonance imaging, with
      the recent addition of positron emission tomography and endoscopic ultrasound.
      The following article discusses the merits of these imaging modalities and their
      role in the workup of patients with lung cancer.

PMID- 9280219
TI  - Lung cancer chemoprevention and management of carcinoma in situ.

PMID- 9280221
TI  - Surgery for early stage non-small cell lung cancer.

PMID- 9280222
TI  - Radiation therapy in the management of patients with unresectable stage IIIA and
      IIIB non-small cell lung cancer.
AB  - Treatment of patients with unresectable stage IIIA and IIIB non-small cell lung
      cancer with conventional radiation therapy has resulted in poor local control, a
      high rate of systemic failure, and 5-year survival of less than 10%. Recent
      modification in radiation treatment planning, dose delivery, and fractionization
      has demonstrated significantly improved median and 2-year survival, comparable in
      some trials to that achieved with induction chemotherapy followed by radiation.
      Current trials focus on combining systemic therapy with dose-intense radiation
      therapy to improve with local and systemic control.

PMID- 9280223
TI  - Combined modality therapy of non-small cell lung cancer.
AB  - Combined modality therapy of locally advanced non-small cell lung cancer has
      become a widely used means of treatment with several reports of benefit found in
      randomized phase III trials. Progress in this area may, however, be less
      substantive than it appears. Phase III trials routinely take the better part of a
      decade to initiate, complete, and analyze, and the flood of phase II trials are
      largely unable to be compared because of a widespread failure to systematically
      use readily available staging techniques.

PMID- 9280225
TI  - Management strategies for recurrent non-small cell lung cancer.
AB  - Because the benefit of first-line chemotherapy for non-small cell lung cancer
      (NSCLC) may be marginal, the use of chemotherapy in the second-line setting for
      the patient who has failed primary platinum-containing chemotherapy (PCC) is
      similarly debatable. The most experience with second-line chemotherapy for NSCLC
      is with docetaxel. Two identical studies enrolled 88 good performance status (PS)
      patients with NSCLC resistant or refractory to prior PCC. The partial response
      rate was 17%, median survival was 39 weeks, and the 1-year survival rate was 40%
      (compared with historical controls who had median and 1-year survivals of 16
      weeks and 16% [P = .003]). Second-line activity of paclitaxel is less clearly
      defined: three trials are negative, two are equivocal, and one is positive.
      Comparison of these studies is difficult, however, because of varying drug
      doses/schedules, small sample sizes, and/or incomplete data. Median and 1-year
      survivals (available in two studies) were 17 weeks and 16%. Other agents active
      against NSCLC have been disappointing in the secondline setting, including
      vinorelbine, irinotecan, vindesine, mitomycin, and etoposide. In conclusion,
      docetaxel (and perhaps paclitaxel) may offer some benefit to NSCLC patients whose
      disease has failed initial PCC. However, the routine use of second-line
      chemotherapy with a taxane should probably be limited to patients with PS of 0 or
      1 only.

PMID- 9280224
TI  - Chemotherapy for advanced non-small cell lung cancer: past, present, and future.
AB  - Until recently, chemotherapeutic intervention in advanced and metastatic non
      small cell lung cancer (NSCLC) has been viewed with a certain degree of nihilism.
      Although meta-analysis of randomized clinical studies from the 1970s and 1980s
      comparing cisplatin-based chemotherapy to best supportive care in metastatic
      NSCLC showed improvement in survival, it was modest at best. A number of novel
      agents have been developed with significant activity against NSCLC in the past 5
      to 6 years and are being incorporated into the therapy of this disease. These
      agents include paclitaxel, docetaxel, vinorelbine, gemcitabine, and irinotecan.
      Clearly there has been improvement in response rates, and in some cases the
      responses have been durable with an increase in the number of 1- and 2-year
      survivors. The next generation of studies has evaluated combinations of these
      novel agents with either cisplatin or carboplatin for patients with NSCLC and the
      results have been provocative, with 1-year survival rates as high as 54%. A
      randomized phase III study of the Eastern Cooperative Oncology Group has shown
      the superiority of paclitaxel-cisplatin regimens over etoposide-cisplatin for
      patients with advanced and metastatic NSCLC. The vinorelbine-cisplatin regimen
      has also proven to have significant, albeit modest benefit in survival when
      compared with cisplatin alone. These combination regimens have now become the
      reference regimens in ongoing randomized studies. There is continued interest in
      developing new agents, or selective approaches that effect novel targets with the
      hope of showing improved therapeutic activity. Some of these approaches include
      gene therapy, monoclonal antibodies, and introduction of antisense
      oligodeoxynucleotides. With better understanding of the molecular and cellular
      biology of lung cancer, the hope for the future is to combine the mechanistic
      approaches with new drug development to define an effective, optimal, and
      definitive regimen for NSCLC.

PMID- 9280226
TI  - Current management of small cell lung cancer.
AB  - There will be approximately 45,000 new cases of small cell lung cancer (SCLC)
      this year. Despite the initial sensitivity to chemotherapy, only 10% of all SCLC
      patients will have significant long-term survival. Studies have yet to show
      significant survival advantage for maintenance chemotherapy, and it appears that
      four to six cycles of chemotherapy is as effective as longer durations of
      chemotherapy. There is as yet no defined role for dose increase in the treatment
      of SCLC. In extensive disease no one chemotherapy combination has shown a
      definitive survival advantage, although it appears that single-agent oral
      etoposide may be inferior to combination intravenous chemotherapy. In limited
      disease, however, cisplatin plus etoposide alone or in alternation with
      cyclophosphamide, doxorubicin, and vincristine is superior to other approaches.
      Also, in limited disease, chemotherapy plus radiotherapy is superior to
      chemotherapy alone and it appears that early concurrent radiotherapy may be the
      ideal approach. Myeloid growth factors should not be given concurrently with
      thoracic radiotherapy. There are several new agents with significant activity in
      SCLC awaiting further study.

PMID- 9280227
TI  - Prophylactic cranial irradiation in small cell lung cancer: rationale, results,
      and recommendations.
AB  - The utility of prophylactic cranial irradiation (PCI) in patients with small cell
      lung cancer (SCLC) constitutes one of the longest running debates in oncology.
      Despite dozens of prospective and retrospective studies and decades of individual
      experience, a consensus has been reached on only two issues: (1) when
      administered to all patients with SCLC, PCI decreases the likelihood of
      developing brain metastases by about half, but (2) PCI does not significantly
      prolong survival. Uncertainty persists over many critical questions, including
      whether, when, and how to administer PCI; whether identifiable subgroups of
      patients benefit more tangibly from PCI; how frequent and severe the long-term
      side effects of PCI are; whether withholding treatment until brain metastases are
      diagnosed is clinically responsible and cost effective; and how newer forms of
      treatment for brain metastases should be integrated into the picture. In this
      review, we discuss the epidemiology and natural history of brain metastases in
      patients with SCLC, the results of studies examining the efficacy of PCI, data on
      the early and late toxicities of PCI, and the status of alternative therapies for
      patients with brain metastases from SCLC. Based on this information, an approach
      to newly diagnosed patients is suggested, and recommendations for future study
      are made.

PMID- 9280228
TI  - Small cell lung cancer in the elderly patient.
AB  - Small cell lung cancer (SCLC) is primarily a disease of older individuals. Many
      physicians and patients believe that lung cancer is less treatable in the elderly
      because of the presence of comorbid illnesses and an unwarranted concern for the
      patient's psychological well being. In reality, the prognostic relevance of age
      is not well defined. Older patients who are able to tolerate standard doses of
      chemotherapy appear to experience survival that is not substantially different
      from that achieved in younger patients. However, older patients who cannot
      tolerate the rigors of standard chemotherapy do less well for reasons that are
      still incompletely understood. Based on these observations, it has been suggested
      that specific therapeutic regimens that result in less toxicity but maintain
      adequate efficacy are needed for older SCLC patients, especially those who have a
      poor performance status. Single agents such as oral etoposide or carboplatin have
      been advocated in this setting because of their perceived efficacy and lower
      toxicity. However, recent randomized studies indicate that older patients should
      be treated with the same regimens that are used for their younger counterparts.
      Single agents may be inadequate to achieve optimal results. A more prudent
      strategy may be one based on an estimate of the individual's likelihood of
      experiencing toxicity. Parameters for selecting patients who are at high risk for
      treatment-related complications are reviewed in this article.

PMID- 9280229
TI  - Second lung cancers in patients successfully treated for lung cancer.
AB  - The rate of developing second lung cancers and other aerodigestive tumors in
      patients who have been treated for both small cell lung cancer (SCLC) and non
      small cell lung cancer (NSCLC) is approximately 10-fold higher than other adult
      smokers. The risk of second lung cancers in patients surviving resection of NSCLC
      is approximately 1% to 2% per year. The series reported show that the patients
      who develop second NSCLCs tend to have early-stage NSCLC (predominantly stage I
      and II). The survival of patients after the second resection of lung cancer is
      similar to that of patients presenting with initial NSCLC. The risk of second
      lung cancers in patients surviving SCLC is 2% to 14% per patient per year and
      increases two- to seven-fold with the passage of time from 2 to 10 years. The
      risk of second lung cancers in patients treated for SCLC appears to be higher
      than that found in patients with NSCLC who were treated only with surgical
      resection. In addition, the chances of successful resection of second primary
      NSCLCs in patients who were treated for SCLC is much less than that for patients
      with metachronous lung cancers after an initial NSCLC. Patients treated for SCLC
      who continue to smoke cigarettes increase their rate of developing second lung
      cancers. The contribution of chest radiation and chemotherapy administration to
      the risk of developing second lung tumors remain to be defined but may be
      responsible for some of the increased risk in patients treated for SCLC compared
      to patients undergoing a surgical resection for NSCLC.

PMID- 9280230
TI  - The future of vascular and interventional radiology.

PMID- 9280231
TI  - Chest radiography.

PMID- 9280232
TI  - 1996 RSNA Eugene P. Pendergrass New Horizons Lecture. Image-guided procedures and
      the operating room of the future.

PMID- 9280233
TI  - Lung volume reduction surgery: let the trials begin.

PMID- 9280234
TI  - Peripherally inserted central catheters: experience in 523 children.
AB  - PURPOSE: To evaluate prospectively the use of peripherally inserted central
      catheters in a large pediatric population. MATERIALS AND METHODS: During a 3-year
      period, data were collected prospectively on 523 consecutive attempts to place
      peripherally inserted central catheters in children. Patients underwent
      radiologically guided placement because attempts were unsuccessful on the
      inpatient units or a patient request was made. Fluoroscopy with use of contrast
      material and venography were used to place catheters and document the position of
      the catheter tip. Follow-up data were collected until treatment cessation or
      catheter removal. RESULTS: Among 523 attempts, 486 (92.9%) catheters were
      successfully placed. In the 37 (7.1%) unsuccessful cases, more than half of these
      children were younger than 24 months of age or weighed less than 5 kg. Ages of
      patients in whom 523 placement attempts were made ranged from 3 weeks to 18 years
      (mean, 6.9 years). Catheters were in place from 1 to 390 days (mean, 20 days).
      Frequency of infection was 1.9% (nine cases); incidence of infection was 0.93 per
      1,000 catheter-placement days. There were two cases (0.4%) of central venous
      thrombosis. Most patients were discharged within 2 days of catheter placement.
      CONCLUSION: Fluoroscopically guided placement of peripherally inserted central
      catheters is a safe and effective method for establishing intermediate- and long
      term central venous access in the pediatric population.

PMID- 9280235
TI  - Peripherally inserted central catheters in infants and children.
AB  - PURPOSE: To determine prospectively the feasibility, complications, and mid- and
      long-term advantages of peripheral insertion of central catheters in infants and
      children. MATERIALS AND METHODS: During a 15-month period between March 1995 and
      June 1996, a total of 285 catheter placement attempts were made to peripherally
      insert central catheters in 183 pediatric patients (89 boys, 94 girls).
      Phlebographic guidance was used, and the catheters were inserted below the elbow
      in 99% of cases. Catheter insertion was indicated for prolonged antibiotic
      therapy in 108 patients (158 catheter placement attempts), hematologic or
      oncologic care in 24 patients (40 attempts), total parenteral nutrition in 16
      patients (46 attempts), and venous access for fluid or blood in 35 patients (41
      attempts). The success rate and complications were recorded along with the
      indication, patient age, and duration of catheter placement. RESULTS: One hundred
      fifty-two of 158 (96%) catheter placement attempts were successful in outpatients
      (n = 108), 124 of 127 (98%) in hospitalized patients (n = 75), and 70 of 73 (96%)
      in patients aged less than 1 year. Infection and pericatheter venous thrombosis
      were the main complications and were seen in 17 of 276 (6%) and one of 276 (0.3%)
      catheter placement attempts, respectively. Catheter occlusion occurred in 23 of
      276 (8%) catheter placement attempts. CONCLUSION: Peripheral insertion of central
      catheters was highly feasible in infants and children with this protocol. Such
      catheters were well tolerated in the pediatric population with a low frequency of
      complications.

PMID- 9280236
TI  - Wilms tumor imaging: patient costs and protocol compliance.
AB  - PURPOSE: To evaluate the patient costs for imaging and compliance with imaging
      protocols in pediatric patients in the National Wilms Tumor Study (NWTS) IV.
      MATERIALS AND METHODS: The medical and imaging records of 60 patients (28 male,
      32 female; aged 3 days to 12.6 years) in NWTS IV were reviewed. Initial imaging
      and follow-up imaging were evaluated separately. Three levels of follow-up
      compliance were evaluated. RESULTS: The total patient cost for imaging was
      $442,180: $94,212 for initial and $347,968 for follow-up studies. Many areas of
      potential cost savings were identified. Protocol compliance was variable. Seventy
      five percent of patients underwent studies in full compliance with the initial
      protocol requirements. For follow-up, compliance was 0%-80% for different studies
      at different compliance levels. For no study was compliance 100%. CONCLUSION:
      Imaging costs in pediatric patients with Wilms tumor are substantial. Protocol
      compliance was not optimal.

PMID- 9280237
TI  - Fetal central nervous system anomalies: MR imaging augments sonographic
      diagnosis.
AB  - PURPOSE: To evaluate fetuses with sonographically suspected central nervous
      system anomalies to determine the frequency with which obstetric magnetic
      resonance (MR) imaging adds clinically useful information to that provided by
      ultrasonography (US). MATERIALS AND METHODS: US and MR images and diagnoses in 18
      pregnant women were reviewed and compared by two radiologists. Postnatal physical
      examination and imaging findings and fetal autopsy results were standards.
      Referring physicians were questioned as to how the additional information
      provided by MR imaging changed patient counseling. RESULTS: In 10 (55%) patients,
      MR imaging demonstrated 11 additional findings. These findings were agenesis of
      the corpus callosum (n = 4), cerebellar hypoplasia (n = 2), cortical cleft (n =
      2), polymicrogyria (n = 1), porencephaly (n = 1), and partial agenesis of the
      septi pellucidi (n = 1). In seven (39%) patients, additional information provided
      by MR imaging altered counseling. In one case of suspected agenesis of the corpus
      callosum, diagnosis at MR imaging was at least partially incorrect. CONCLUSION:
      US and MR imaging are complementary imaging methods in the evaluation of high
      risk pregnancy. When a central nervous system anomaly is suspected at US, MR
      imaging may demonstrate additional findings that can alter patient counseling.

PMID- 9280238
TI  - Pulmonary complications in children with hematologic malignancies: accuracy of
      diagnosis with chest radiography and CT.
AB  - PURPOSE: To determine the diagnostic accuracy of chest radiography and computed
      tomography (CT) in patients with complications during treatment for hematologic
      malignancies. MATERIALS AND METHODS: CT scans were obtained 1 week or less before
      bronchoscopic sampling or biopsy in 48 pediatric patients (age range, 8 months to
      18 years at diagnosis) undergoing treatment for leukemia, lymphoma, or
      myeloproliferative disease. Radiographs were obtained less than 1 week before CT.
      Pulmonary complications comprised fungal (n = 11), viral (n = 4), and bacterial
      (n = 5) pneumonias; cryptogenic organizing pneumonia ([COP] n = 4); and pulmonary
      tumor (n = 4). Chest radiographs and CT scans were rated independently by three
      radiologists who were unaware of these diagnoses. RESULTS: Satisfactory
      diagnostic accuracy, defined by the area under the receiver operating
      characteristic (ROC) curve, was noted for fungal pneumonia (radiography, ROC area
      = 0.82; CT, ROC area = 0.78), COP (radiography, ROC area = 0.75; CT, ROC area =
      0.75), and pulmonary tumor (radiography, ROC area = 0.73; CT, ROC area = 0.83).
      Generalizability was good for fungal pneumonia (radiography, generalizability
      coefficient [GC] = 0.84; CT, GC = 0.84) and COP (radiography, GC = 0.75; CT, GC =
      0.99). There was no statistically significant difference in diagnostic accuracy
      between radiography and CT for any of the diagnoses. CONCLUSION: Radiography and
      CT have satisfactory accuracies for fungal pneumonia and COP. For these
      conditions, CT identified more true-positive cases than did radiography.

PMID- 9280239
TI  - Lymphangiomas in children: percutaneous sclerotherapy with an alcoholic solution
      of zein.
AB  - PURPOSE: To determine the efficacy of percutaneous sclerotherapy with an
      alcoholic solution of zein in lymphangiomas in pediatric patients. MATERIALS AND
      METHODS: Fourteen patients with macrocystic and mixed lymphangiomas were treated
      with use of Ethibloc as a sclerosing agent. The procedure was performed with
      ultrasonographic and/or fluoroscopic guidance. Follow-up clinical and sequential
      computed tomographic examinations were performed to evaluate regression of the
      lesion. RESULTS: Regression was excellent in nine (64%) of the 14 lesions:
      Regression was complete in four lymphangiomas and was to less than 5% of the
      initial volume in five. Satisfactory results were obtained in the remaining five
      (36%) of 14 lesions. The most frequent complication was leakage of Ethibloc
      without important sequelae in 10 of the 14 lymphangiomas. CONCLUSION:
      Percutaneous sclerotherapy with Ethibloc was a safe and effective procedure in
      the treatment of macrocystic and mixed lymphangiomas.

PMID- 9280240
TI  - Intradecidual sign: is it effective in diagnosis of an early intrauterine
      pregnancy?
AB  - PURPOSE: To determine if the intradecidual sign at sonography is effective in the
      diagnosis of early intrauterine pregnancy. MATERIALS AND METHODS: In 102 pregnant
      patients, transvaginal sonography revealed an intrauterine fluid collection
      without a yolk sac or embryo. Four observers (experienced sonologist, body
      imaging fellow, 1st-year radiology resident, and premedical student) determined
      independently whether the intradecidual sign was absent, present, or
      indeterminate. Interpretations were limited to visualization of only the uterus.
      RESULTS: Follow-up revealed intrauterine pregnancy in 91 patients (outcome normal
      in 48 and abnormal in 43) and ectopic pregnancy in 11 patients. Among the four
      reviewers, sensitivity for diagnosis of an intrauterine pregnancy was 34%-66%,
      specificity was 55%-73%, accuracy was 38%-65%, positive predictive value was 91%
      93%, and negative predictive value was 12%-16%. Three to five ectopic pregnancies
      were categorized incorrectly as demonstrating the intradecidual sign, depending
      on the reviewer. CONCLUSION: The intradecidual sign does not appear to be
      sensitive or specific in diagnosis of an early intrauterine pregnancy. When an
      intrauterine fluid collection is present without an embryo or yolk sac (with
      positive pregnancy test results), a follow-up sonogram should be obtained unless
      contraindicated clinically.

PMID- 9280241
TI  - Fine-needle biopsy specimens of benign breast lesions distinguished from invasive
      cancer ex vivo with proton MR spectroscopy.
AB  - PURPOSE: To determine whether invasive breast cancer can be distinguished from
      benign lesions with proton magnetic resonance (MR) spectroscopy ex vivo on the
      basis of altered cellular chemistry. MATERIALS AND METHODS: Two hundred eighteen
      fine-needle biopsy specimens were obtained in 191 patients undergoing surgery and
      were analyzed with proton MR spectroscopy. MR spectroscopic and histopathologic
      findings were compared. RESULTS: Invasive carcinoma produced increased signal at
      3.25 ppm, attributable to choline-containing metabolites. Discrimination between
      invasive carcinoma (n = 82), benign lesions (n = 106), or carcinoma in situ (n =
      17) was based on the resonance intensity at 3.25 ppm standardized to the
      resonance at 3.05 ppm (P < .001). The ratio of peak height intensities of
      resonances at 3.25 to those at 3.05 ppm was less than 1.7 in 102 of the 106
      normal or benign lesions. All carcinoma in situ specimens with comedonecrosis or
      a microinvasive component (n = 6) were categorized at MR spectroscopy with
      invasive carcinoma, while others with in situ disease alone were categorized with
      benign lesions (n = 11). The sensitivity and specificity of MR spectroscopy in
      fine-needle biopsy specimens in distinguishing benign lesions from invasive
      cancer were 95% and 96%, respectively. CONCLUSION: Proton MR spectroscopy of fine
      needle biopsy specimens provides objective diagnostic information that
      complements findings of conventional preoperative investigations of breast
      lesions.

PMID- 9280242
TI  - Interventional breast MR imaging: clinical use of a stereotactic localization and
      biopsy device.
AB  - PURPOSE: To evaluate the usefulness of preoperative magnetic resonance (MR)
      imaging-guided stereotactic localization and core biopsy of suspicious breast
      lesions that are visible at breast MR imaging alone (ie, that are clinically,
      mammographically, and ultrasonographically occult), with the goal of integrating
      this technique into the diagnostic and therapeutic work-up of MR-suspicious
      lesions in a clinical setting. MATERIALS AND METHODS: A stereotactic breast
      biopsy device was used for needle placement in and guide wire localization of 97
      lesions in 66 patients or core biopsy of five lesions in five patients; all
      lesions were visible at MR imaging. Interventions were performed with MR guidance
      on a 0.5- or 1.5-T system. RESULTS: Lesion localization and resection were
      successful in 95 of the 97 lesions; two of the lesions were not resected in spite
      of correct guide wire localization. In this series, 53 (55%) of 97 lesions proved
      malignant (11 [21%] in situ; 42 [79%] invasive). Lesions were 4-19 mm (mean, 8.7
      mm); all invasive cancers corresponded to a pT1 tumor stage. Location of the
      lesion in the parenchyma (retroareolar or prepectoral) did not interfere with
      accessibility. CONCLUSION: MR imaging-guided stereotactic hook-wire placement and
      excisional biopsy are accurate and effective in managing lesions identified at
      only breast MR imaging. MR imaging-guided core biopsy holds promise for allowing
      a definite work-up of these lesions.

PMID- 9280243
TI  - Needle-localized breast biopsy: why do we fail?
AB  - PURPOSE: To determine what factors are associated with unsuccessful needle
      localized breast biopsy (NLBB). MATERIALS AND METHODS: Findings in 280
      consecutive nonpalpable breast lesions in 262 women (age range, 27-87 years; mean
      age, 55 years) who underwent nonstereotactic, mammographically guided,
      standardized NLBB were retrospectively analyzed according to mammographic lesion
      type, lesion size, number of lesions per breast, needle type, proximity of needle
      to lesion, radiologist, specimen size, surgeon, and histologic findings. RESULTS:
      Biopsy failed in seven (2.5%) of 280 lesions. Failures were related to lesion
      type, lesion size, number of lesions per breast, accuracy of needle placement,
      and volume of tissue removed. Removal of more than one tissue specimen converted
      failure to success in 14 (67%) of 21 initially missed lesions, all
      microcalcifications. CONCLUSION: Unsuccessful NLBB was more likely with two
      lesions per breast, small lesions, small specimens, and microcalcifications.
      Piercing such lesions with the localizing needle led to successful biopsy.
      Removal of more tissue was helpful with missed microcalcifications.

PMID- 9280244
TI  - Lung volume reduction surgery: comparison of preoperative radiologic features and
      clinical outcome.
AB  - PURPOSE: To examine the relationship between preoperative radiologic findings and
      clinical outcome after lung volume reduction surgery. MATERIALS AND METHODS: In
      50 consecutive patients, preoperative chest radiographs and computed tomographic
      (CT) scans were scored by four radiologists for features related to the severity
      and distribution of emphysema and compared with clinical improvement in forced
      expiratory volume in 1 second (FEV1), arterial partial pressure of oxygen, and
      exercise tolerance 6 months after surgery. RESULTS: In the 47 surviving patients,
      follow-up data showed greater postoperative improvement in function in patients
      with a global pattern of predominantly upper-lobe emphysema (P < .05) and in
      patients with a more heterogeneous distribution of emphysema, compressed lung,
      and a larger percentage of normal and mildly emphysematous lung (P < .05 for
      improvement in FEV1). Radiographic scores for individual features were more
      strongly correlated with outcome than CT scores. The combination of upper-lobe
      severity and percentage of normal and mildly emphysematous lung at CT were the
      strongest predictors of improvement in FEV1 (r2 = .49). The three patients who
      died were older (P = .05) and had more severe, diffuse emphysema compared with
      other patients. CONCLUSION: Imaging studies may help predict the degree of
      improvement and therefore should be considered an integral part of an objective
      patient selection process. Radiography alone may be adequate for initial
      screening.

PMID- 9280245
TI  - Chronic thromboembolism: diagnosis with helical CT and MR imaging with
      angiographic and surgical correlation.
AB  - PURPOSE: To evaluate the accuracy of identification of central and segmental
      chronic thromboembolic disease on helical computed tomographic (CT) scans and on
      magnetic resonance (MR) images. MATERIALS AND METHODS: Radiologic findings in 55
      patients suspected of having chronic thromboembolic pulmonary hypertension were
      analyzed; these included findings from angiography (n = 55), helical CT (n = 47),
      and MR imaging (n = 26). Forty patients underwent thromboendarterectomy. CT and
      MR images were independently interpreted by two readers for the presence of
      thromboembolic material in central and segmental vessels. Surgical findings and
      angiographic findings were the reference standards for disease in central and
      segmental vessels, respectively. RESULTS: Central vessel disease was determined
      more accurately with helical CT scans (accuracy of 0.79 for each of the two
      readers) than with angiograms (accuracy of 0.74) or with MR images (accuracy of
      0.39 and 0.46 for two readers). Segmental vessel disease was also more accurately
      determined with CT scans (accuracy of 0.75 and 0.76 for two readers) than with MR
      images (accuracy of 0.61 and 0.57 for two readers). CONCLUSION: Helical CT is a
      useful alternative to conventional angiography for diagnosis of chronic
      thromboembolism but may not be sufficient for selecting candidates for surgery in
      all cases.

PMID- 9280246
TI  - Depiction of pulmonary emboli with spiral CT: optimization of display window
      settings in a porcine model.
AB  - PURPOSE: To determine optimal spiral computed tomographic (CT) image display for
      depiction of pulmonary emboli (PE). MATERIALS AND METHODS: Autologous PE detected
      in 10 pigs with contrast material-enhanced spiral CT were displayed with six
      display window settings (standard mediastinal window and five modified windows
      referenced to attenuation values in pulmonary artery [PA] branches). The thrombus
      gray level and gray level contrast and separability of PE versus those of the
      local PA branch were computed for each window setting; results were compared with
      repeated measured analysis of variance. RESULTS: Of 114 PE detected
      pathologically, 28 were visible with spiral CT. Two of the 28 PE were not
      detectable with standard mediastinal windows. Statistically significantly
      improved gray level contrast and separability were noted with modified windows
      referenced to the second-order PA branch and the local PA branch than with the
      standard mediastinal and other modified window settings (P < .05). However,
      thrombus gray level was statistically significantly higher with the standard
      mediastinal window (P < .05). CONCLUSION: PE are best depicted as filling defects
      when displayed with a modified window referenced to the right or left main PA
      attenuation. Standard mediastinal windows are useful for identifying vessels that
      are occluded completely with PE.

PMID- 9280247
TI  - Distal appendicitis: CT appearance and diagnosis.
AB  - PURPOSE: To determine the appearance of appendicitis in the distal part of the
      organ (distal appendicitis) on computed tomographic (CT) scans and to evaluate
      the accuracy of diagnosis based on CT findings. MATERIALS AND METHODS: CT scans
      and medical records in 180 consecutive patients with proved appendicitis were
      reviewed. Fourteen had distal appendicitis with at least a 3-cm length of normal
      proximal appendix. Appendiceal CT scans and initial reports were reviewed
      retrospectively. RESULTS: The proximal appendix was collapsed (n = 6) or was
      filled with contrast material (n = 6) or air (n = 2). Inflamed distal appendices
      averaged 13.2 mm in diameter and were associated with periappendiceal fat
      stranding (n = 14), adenopathy (n = 6), appendolith(s) (n = 4), or fluid (n = 2).
      Transition points consisted of a progressively narrowed appendiceal lumen and
      thickened wall (n = 5) or appendiceal diameter enlargement (n = 9). No cecal
      apical changes were seen. Scans in all 14 patients were prospectively interpreted
      as indicative of appendicitis, including 12 (86%) interpreted as indicative of
      distal appendicitis. CONCLUSION: CT findings are useful for the accurate
      diagnosis of distal appendicitis. Visualization of the proximal appendix alone is
      insufficient to exclude distal appendicitis.

PMID- 9280248
TI  - Primary epiploic appendagitis: evolutionary changes in CT appearance.
AB  - PURPOSE: To determine the changes in the computed tomographic (CT) appearance of
      primary epiploic appendagitis. MATERIALS AND METHODS: Clinical records and CT
      scans were reviewed in 10 patients who were initially suspected of having
      diverticulitis or appendicitis but were later determined to have primary epiploic
      appendagitis. The scans were obtained at the time of presentation and at follow
      up 1-84 weeks later. RESULTS: Initial CT characteristics included mean size of 14
      x 21 mm, oval (n = 9) or round (n = 1) shape, mean attenuation of -53 HU,
      visceral (n = 10) or parietal (n = 7) peritoneal thickening, periappendageal fat
      stranding (n = 10), adjacent bowel wall thickening (n = 4) or compression (n =
      2), and central high-attenuating dot (n = 2). Follow-up CT characteristics
      included residual abnormality (n = 9); mean size of 10 x 15 mm; oval (n = 6),
      round (n = 2), or indistinct (n = 1) shape; mean attenuation of -68 HU; visceral
      (n = 5) or parietal (n = 3) peritoneal thickening; periappendageal fat stranding
      (n = 1); and central high-attenuating dot (n = 1). CT characteristics of the
      remnant lesion included smaller lesion with fat attenuation (n = 6), nugget with
      soft-tissue attenuation (n = 2), and nondescript fat stranding (n = 1).
      CONCLUSION: Awareness of the CT appearance of acute and healing primary epiploic
      appendagitis may help in the differential diagnosis of pericolonic abnormality.

PMID- 9280249
TI  - Liver hemangioma: US-guided 18-gauge core-needle biopsy.
AB  - PURPOSE: To assess the clinical usefulness of ultrasound (US)-guided, 18-gauge
      core-needle biopsy of liver hemangiomas performed with a one-hand automatic
      sampling technique. MATERIALS AND METHODS: In 491 US-guided core-needle biopsies
      of the liver, hemangioma was suspected at US in 51 cases. Hemangiomas were
      confirmed histologically in 29 cases, a malignant lesion was revealed in six
      cases, and no specific diagnosis could be made in 16 cases. Hemangioma was
      diagnosed in 18 lesions that appeared malignant at US. The hemangiomas were 7-114
      mm in diameter (mean, 45 mm). RESULTS: The histologic diagnosis of hemangioma was
      unequivocal in 47 biopsy specimens. A cuff of normal hepatic parenchyma could be
      interposed between the capsule and the margin of the hemangioma in all procedures
      but one, in which two direct punctures were made of a protruding giant
      hemangioma. An average of 1.4 punctures were performed at each biopsy session.
      There were no false-positive findings and 15 or perhaps 16 false-negative
      findings. There were no serious complications. CONCLUSION: US-guided core needle
      biopsy seems to be a safe procedure when the diagnosis of hemangioma must be
      ascertained. Conclusive biopsy findings may shorten the diagnostic work-up,
      benefiting the patient and the hospital.

PMID- 9280250
TI  - Gallbladder disease: appearance of associated transient increased attenuation in
      the liver at biphasic, contrast-enhanced dynamic CT.
AB  - PURPOSE: To evaluate the frequency, location, and appearance of transient
      increased attenuation in the liver during arterial-phase helical or incremental
      computed tomography (CT) in patients with gallbladder disease without hepatic
      extension. MATERIALS AND METHODS: Findings in dynamic CT examinations in 31
      patients with surgically proved gallbladder disease not extending into the liver
      and in 31 control patients without gallbladder disease were retrospectively
      reviewed and correlated with findings in other imaging examinations. RESULTS:
      Areas of transient increased hepatic attenuation (n = 27) were identified in 22
      of 31 patients with gallbladder disease and in only one of 31 control patients.
      The difference in these findings was statistically significant (P < .001). In the
      27 areas of transient increased hepatic attenuation, these findings were
      categorized as curvilinear or nodular attenuation adjacent to the gallbladder
      fossa in 13 (48%), segmental or subsegmental attenuation in segment IV and/or V
      in seven (26%), lobar attenuation in the left lobe (segments II-IV) in four
      (15%), and nodular attenuation seen as an early enhancing "pseudolesion" in
      segment IV in three (11%). Hepatic angiography performed in 10 of the 22 patients
      showed early depiction of the dilated cystic vein (n = 8) and direct
      communication with the portal branches (n = 2). CONCLUSION: Transient increased
      attenuation in the liver had a variable appearance at dynamic arterial-phase CT
      in most patients with gallbladder disease. This attenuation was most likely due
      to increased blood flow from the hepatobiliary system.

PMID- 9280251
TI  - Hepatic lesions: discrimination of nonsolid, benign lesions from solid, malignant
      lesions with heavily T2-weighted fast spin-echo MR imaging.
AB  - PURPOSE: To determine whether the combined use of heavily and moderately T2
      weighted fast spin-echo magnetic resonance (MR) images improves differentiation
      of non-solid, benign hepatic lesions from solid malignancies. MATERIALS AND
      METHODS: Three radiologists reviewed moderately (n = 133) and heavily (n = 133)
      T2-weighted and multiphasic dynamic contrast material-enhanced (n = 93) MR images
      in 133 patients with proved focal hepatic lesions (95 benign, 38 malignant). The
      radiologists used a five-point scale to rate their confidence in determination of
      malignancy. RESULTS: All three reviewers were statistically significantly better
      able to differentiate small (diameter less than 3 cm; n = 84) benignancies from
      small malignancies with the combination of moderately and heavily T2-weighted
      images (area under the receiver operating characteristic curve, 0.99 for each
      reader) than with moderately T2-weighted images alone (area, 0.88-0.90; P < .05).
      Confident diagnoses were rendered in 69 (82%) patients, with 100% accuracy for
      the combined use of moderately and heavily T2-weighted images. For larger lesions
      (diameter 3 cm or larger; n = 49), accurate differentiation was possible with
      moderately T2-weighted images alone. Additional use of multiphasic images did not
      improve the sensitivity, specificity, or accuracy of image interpretation.
      CONCLUSION: The combined use of moderately and heavily T2-weighted fast spin-echo
      MR images improves differentiation of small benign hepatic lesions from small
      malignant lesions.

PMID- 9280252
TI  - Focal liver masses: characterization with diffusion-weighted echo-planar MR
      imaging.
AB  - PURPOSE: To evaluate diffusion-weighted echo-planar magnetic resonance (MR)
      imaging for improving the specificity of characterization of liver tumors.
      MATERIALS AND METHODS: Diffusion-weighted echo-planar imaging was performed with
      a 1.5-T whole-body imager with use of a body phased-array coil in 51 patients
      with 59 hepatic masses (41 malignant tumors, nine hemangiomas, and nine cysts).
      Apparent diffusion coefficient (ADC) values were obtained with two motion-probing
      gradients (b = 30 and 1,200 sec/mm2) during each of the breath-hold periods, and
      an ADC map was constructed. The T2 was derived from spin-echo echo-planar images
      with echo times of 47 and 99 msec. RESULTS: The ADC value of malignant masses
      (1.04 x 10(-3) mm2/sec) was significantly lower (P < .01) than that of benign
      masses (hemangiomas [1.95 x 10(-3) mm2/sec] and cysts [3.05 x 10(-3) mm2/sec]),
      although the T2s showed considerable overlap. A small amount of overlap in ADC
      values occurred among malignant tumors, hemangiomas, and cysts. ADC values of two
      cystic masses from ovarian carcinomas were within the range of those of
      hemangiomas. CONCLUSION: These preliminary results indicate that diffusion
      weighted MR imaging can be useful in characterizing focal liver masses. With the
      exception of cystic metastatic tumors, the technique may be especially useful in
      tumors that appear markedly hyperintense on T2-weighted images due to a long T2.

PMID- 9280253
TI  - Duodenal gangliocytic paraganglioma: CT, MR imaging, and US findings.
AB  - PURPOSE: To determine the imaging features of duodenal gangliocytic paraganglioma
      that can be used to differentiate this mass from other lesions. MATERIALS AND
      METHODS: Imaging, histopathologic, and surgical findings in five patients with
      proved gangliocytic paraganglioma were reviewed. The most common symptom at
      presentation was abdominal pain (n = 3). All patients underwent computed
      tomography (CT), two underwent ultrasonography (US), and one underwent magnetic
      resonance (MR) imaging. Imaging findings were correlated with findings from
      surgical resection specimens in all cases. RESULTS: All lesions were located
      around the second portion of the duodenum and were 3-13 cm in diameter (mean, 6.5
      cm). Two extended laterally to the duodenum, two extended medially, and one was
      intraluminal. All appeared solid and homogeneous on US, CT, and MR images and had
      homogeneous contrast material enhancement on CT and MR images. All were solid,
      with a prominent vascular network, but no cystic hemorrhage or necrosis was noted
      at pathologic examination. CONCLUSION: The imaging features of gangliocytic
      paraganglioma are suggestive enough for the prospective diagnosis and
      differentiation of this benign mass from other lesions.

PMID- 9280254
TI  - MR imaging of the liver with Resovist: safety, efficacy, and pharmacodynamic
      properties.
AB  - PURPOSE: To evaluate the safety, efficacy, and pharmacodynamic properties of a
      new superparamagnetic parenteral iron oxide contrast agent for magnetic resonance
      (MR) imaging. MATERIALS AND METHODS: Thirty-six patients with liver lesions
      received a bolus injection of Resovist (SH U 555 A; Schering, Berlin, Germany) at
      a dose of 4, 8, or 16 micromol iron per kilogram body weight (micromol Fe/kg).
      Fast low-angle shot, spin-echo, and turbo gradient spin-echo MR images were
      obtained before and 10, 40, and 70 minutes after injection. Blood samples were
      obtained, vital signs were monitored, and adverse events were recorded. Lesion
      detection was assessed by two independent, blinded readers. RESULTS: No drug
      related adverse events occurred. Serum iron and ferritin levels were increased at
      all dose levels. Partial thromboplastin time increased and factor XI level
      decreased 4 hours after injection of 16 micromol Fe/kg. Lesion detection and
      diagnostic confidence were increased in patients who received 4 or 8 micromol
      Fe/kg, with no further increase with a 16-micromol dose. CONCLUSION: Resovist is
      safe and effective. The best MR imaging results were obtained 40 minutes after
      injection of 8 micromol Fe/kg.

PMID- 9280255
TI  - Perigraft inflammation due to Dacron-covered stent-grafts in sheep iliac
      arteries: correlation of MR imaging and histopathologic findings.
AB  - PURPOSE: To evaluate with magnetic resonance (MR) imaging the inflammatory
      perigraft response after implantation of Dacron-covered and noncovered arterial
      endovascular prostheses in sheep. MATERIALS AND METHODS: Four prosthesis types-
      two Dacron-covered nitinol stent-grafts (plain and heparin-coated) and two
      noncovered nitinol stents (Memotherm and Cragg)--were each inserted into the
      external iliac arteries of eight sheep. MR imaging before and after gadolinium
      enhancement was performed 5-8 days and 1 month after implantation (before the
      animals were killed). Macroscopic and microscopic examinations of the vessels
      were performed, and findings were correlated with those on MR images. RESULTS:
      Severe inflammatory perigraft responses to the heparin-coated Dacron-covered
      stent-grafts were found; MR images demonstrated contrast enhancement and edema.
      Macroscopic examination showed marked vascular wall thickening and adhesions
      around the Dacron fabric; microscopic examination showed a pronounced
      inflammatory foreign-body response. There was a moderate inflammatory response to
      the plain Dacron-covered stent-grafts and almost no response to noncovered
      stents. CONCLUSION: In sheep, MR imaging findings of perigraft soft-tissue edema
      and contrast enhancement correlated well with histopathologic findings of severe
      perigraft inflammation due to heparin-coated Dacron-covered stent-grafts.

PMID- 9280256
TI  - Abdominal aortic aneurysm: rupture associated with the high-attenuating crescent
      sign.
AB  - PURPOSE: To determine the histopathologic features of the ruptured abdominal
      aortic aneurysm associated with the high-attenuating crescent sign on computed
      tomographic (CT) scans and to suggest a possible mechanism for the rupture.
      MATERIALS AND METHODS: Histopathologic examination was performed with specimens
      from six patients with a ruptured aneurysm associated with the high-attenuating
      crescent sign and from eight patients with a nonruptured aneurysm and in whom the
      high-attenuating crescent sign was not present. RESULTS: Acute hemorrhage in the
      mural thrombus or aneurysmal wall coincident with the high-attenuating crescent
      sign was present in all six patients with a ruptured aneurysm. Clefts with
      seeping blood in the mural thrombus were seen in four patients with a ruptured
      aneurysm; intact specimens of the mural thrombus were not obtained in two
      patients because the hemorrhagic thrombus was fragile. Clefts with seeping blood
      were scattered from the inner to the outer layers of the mural thrombus. In the
      eight patients with uncomplicated aneurysm, no hemorrhage in the mural thrombus
      or aneurysmal wall was noted, and no clefts were seen. CONCLUSION: The cause of
      high-attenuating crescents in a ruptured aneurysm may be attributed to hemorrhage
      in the mural thrombus or in the aneurysmal wall.

PMID- 9280257
TI  - Intravascular MR imaging of atherosclerotic plaque: ex vivo analysis of human
      femoral arteries with histologic correlation.
AB  - PURPOSE: To assess the potential role of intravascular magnetic resonance (MR)
      imaging with receiver coils mounted to an inflatable balloon in characterizing
      atherosclerotic plaque. MATERIALS AND METHODS: Twelve human harvested segmental
      femoral arteries with atherosclerotic changes were studied with a 5-F imaging
      balloon catheter equipped with a single-loop wire receiver coil. Imaging was
      performed with an open-configuration 0.5-T (n = 6) or a 1.5-T (n = 6) MR system,
      with T1- and T2-weighted sequences. Histologic analysis was the reference
      standard, and MR images were analyzed with regard to vessel wall thickness,
      plaque area, and components. RESULTS: Images acquired at 1.5 T were characterized
      by better in-plane resolution (117 x 104 microm). Resolution at 0.5 T (234 x 178
      microm) was sufficient to discriminate the wall layers. On T2-weighted images,
      adventitia, media, and thickened intima could be discriminated. T1-weighted
      images did not permit differentiation between wall layers. There was good
      correlation between MR and histologic measurements of wall thickness (r = .97)
      and plaque area (r = .98). Plaque characterization was possible on T2-weighted
      images. Calcified plaque was identified as areas of low signal intensity (134 +/-
      98) and could be differentiated from fibrous structures containing collagen
      (1,968 +/- 680) or fatty components (762 +/- 394). CONCLUSION: Intravascular MR
      imaging on the basis of the balloon catheter design enables differentiation of
      wall layers and plaque components.

PMID- 9280258
TI  - Superior mesenteric arterial embolism: local fibrinolytic treatment with
      urokinase.
AB  - PURPOSE: To evaluate the efficacy of intraarterial urokinase in the treatment of
      superior mesenteric arterial (SMA) embolism. MATERIALS AND METHODS: Within 3
      years, 10 patients (six men, four women; aged 62-82 years) with angiographically
      proved SMA emboli were selected on the basis of absence of peritoneal signs of
      intestinal necrosis at physical examination and normal abdominal plain
      radiographs to undergo local lysis with urokinase. RESULTS: The procedure was
      performed without complications in all 10 patients. The embolus was successfully
      lysed in nine patients (90%). Clinical success was achieved in seven patients
      (70%); however, in one patient laparotomy was required to confirm the clinical
      finding. None of these patients had recurrent embolism or postischemic intestinal
      stenosis during follow-up (mean, 11.2 months). The three remaining patients (30%)
      underwent laparotomy subsequent to failure of intraarterial treatment with
      urokinase. CONCLUSION: Fibrinolytic treatment with urokinase may be an effective
      alternative to surgical embolectomy in patients with SMA embolism without
      clinical or radiologic signs of intestinal infarction. In this small series,
      abatement of abdominal pain in the 1st hour of fibrinolytic treatment was the
      best indicator of clinical success. Pain persisted in patients with intestinal
      infarction.

PMID- 9280259
TI  - Left hepaticogastrostomy for biliary obstruction: long-term results.
AB  - PURPOSE: To evaluate the long-term results of peripheral biliary diversion by
      means of anastomoses of the left lobe of the liver to the stomach. MATERIALS AND
      METHODS: Transhepatic perforation of the left lobe of the liver into the lesser
      curvature of the stomach was performed in 35 patients with a presumed diagnosis
      of malignant obstructive jaundice. Jaundice was found to be caused by a malignant
      stricture in 32 patients and a benign stricture in three. Perforation was
      performed under fluoroscopic, endoscopic, and laparoscopic guidance in 33
      patients and without laparoscopy in the other two. The hepaticogastric
      anastomosis was secured with a gastrostomy tube; patency of the tract was
      maintained with placement of a metallic stent. Kaplan-Meier analysis was used to
      evaluate survival, anastomosis patency rate, and jaundice recurrence. RESULTS:
      Technical success was achieved in all patients. Two (6%) patients had anastomotic
      obstruction. The actuarial survival rate was 91%, 80%, 59%, and 26% at 1, 3, 6,
      and 12 months. The mean patency was 234 days +/- 252. The jaundice-free rate
      among surviving patients was 100%, 96%, 93%, and 80% at 1, 3, 6, and 12 months.
      The reintervention rate was 14%. Late cholangitis occurred in seven (20%)
      patients. CONCLUSION: This peripheral diversion procedure appears to be safe and
      shows good long-term patency.

PMID- 9280261
TI  - Obstetric embolotherapy: effect on menses and pregnancy.
AB  - PURPOSE: To determine the long-term effects of uterine embolotherapy with gelatin
      sponge pledgets on menses and fertility. MATERIALS AND METHODS: Between June 1990
      and December 1995, 17 women (aged 20-44 years) with obstetric hemorrhage
      underwent selective gelatin sponge pledget embolization of uterine vessels.
      Gynecologic information in the 12 women who did not undergo hysterectomy was
      obtained by means of direct communication or from the patients' physicians.
      RESULTS: In 11 (92%) of the 12 women, normal menses resumed within 2-5 months of
      the procedure. There were no complications related to embolotherapy. The follow
      up period was 1-6 years. All three patients who desired to conceive had full
      term, healthy newborns. The only patient who is amenorrheic is currently
      receiving medroxyprogesterone acetate; her ultimate menstrual and fertility
      status cannot yet be determined. CONCLUSION: Selective embolization of the
      uterine vessels with gelatin sponge pledgets is a safe and effective method of
      managing pregnancy-related hemorrhage. Our results suggest that women who undergo
      this procedure can expect to have a return of normal menses with no adverse
      effect on fertility.

PMID- 9280260
TI  - Hepatocellular carcinoma with portal vein tumor thrombus: embolization of
      arterioportal shunts.
AB  - PURPOSE: To evaluate transcatheter arterial embolization in patients with
      hepatocellular carcinoma, portal vein tumor thrombus, and arterioportal shunts.
      MATERIALS AND METHODS: Ten patients with hepatocellular carcinoma, portal vein
      tumor thrombus, and severe arterioportal shunting were identified; in these
      patients, portal blood flow before embolization was hepatofugal. Embolization of
      arterioportal shunts was performed with steel coils that were introduced through
      a catheter during arteriography. After embolization, changes in portal
      hemodynamics and clinical signs and performance status of patients were
      evaluated; survival rates of patients with and patients without severe
      arterioportal shunting were compared. RESULTS: In all patients after
      embolization, angiography showed resolution of arterioportal shunting, and
      portography showed hepatopetal blood flow in the portal vein trunk. After
      embolization, performance status of five patients with initial scores of 2 or 3
      improved. Ascites resolved in four patients and improved in four patients. One
      patient died of hepatic failure caused by rupture of esophageal varices 7 days
      after embolization. Median survival was 4.3 months, and the 6-month and 1-year
      survival rates were 45% and 12%, respectively. There were no significant
      differences between survival rates in patients with and patients without severe
      arterioportal shunting. CONCLUSION: Transcatheter arterial embolization of
      arterioportal shunts is a useful treatment for improving quality of life in
      patients with hepatocellular carcinoma.

PMID- 9280262
TI  - Fibroma and fibrothecoma of the ovary: MR imaging findings.
AB  - PURPOSE: To describe the morphologic and signal intensity characteristics on
      magnetic resonance (MR) images of fibromas and fibrothecomas. MATERIALS AND
      METHODS: MR images of 11 female patients with histologically proved fibromas or
      fibrothecomas were reviewed, and morphologic and signal intensity characteristics
      of the lesions were analyzed. MR imaging findings were correlated with histologic
      findings. RESULTS: All fibromas and fibrothecomas showed homogeneous low signal
      intensity on T1-weighted images. On T2-weighted images, the two smallest lesions
      showed homogeneous low signal intensity, and eight of the other nine lesions
      showed predominantly low signal intensity. Edema was noted only in larger
      lesions, and cystic degeneration was noted only in three of the largest lesions.
      On T2-weighted images, the percentage of low signal intensity in the lesion was
      not found to be related to lesion size, and the percentage of low signal
      intensity in fibromas was not significantly different from that in fibrothecomas
      (P = .55). Many lesions showed heterogeneous signal intensity; the solid
      component was distributed peripherally, and the cystic component was located
      centrally or eccentrically. Free intraperitoneal fluid was noted in 10 of 11
      lesions and was not significantly correlated with lesion size (r = .52 and P =
      .10). CONCLUSION: Because of their predominantly low signal intensity on T2
      weighted images, fibromas and fibrothecomas display a relatively specific
      appearance on MR images.

PMID- 9280264
TI  - Collateral ligaments of the elbow: conventional MR imaging and MR arthrography
      with coronal oblique plane and elbow flexion.
AB  - PURPOSE: To determine the best plane and position of the elbow for optimal
      visualization of normal and abnormal collateral ligaments with conventional
      magnetic resonance (MR) imaging and MR arthrography, to determine the normal
      appearance of the collateral ligaments at MR arthrography and to assess use of MR
      arthrography in evaluation of collateral ligamentous lesions. MATERIALS AND
      METHODS: Nine cadaveric elbow specimens were imaged with and without
      intraarticular administration of gadolinium-containing solution in several planes
      that were identified as potentially useful in a pilot study in two specimens. MR
      imaging findings were compared with anatomic findings. RESULTS: Normal and
      abnormal ligaments were best depicted in a 20 degrees posterior oblique coronal
      plane in relation to the humeral shaft with the elbows extended and a coronal
      plane aligned with the humeral shaft with the elbows slightly flexed (20 degrees
      30 degrees of flexion). Gadolinium enhancement improved the delineation of normal
      and abnormal ligaments on T1-weighted images in each case. CONCLUSION: The
      posterior oblique coronal plane with the elbows extended or the coronal plane
      aligned with the humeral shaft with the elbows slightly flexed allows accurate
      assessment of the collateral ligaments. Gadolinium-enhanced MR arthrography of
      the elbow seems to be a promising technique.

PMID- 9280263
TI  - Acutely injured knee: effect of MR imaging on diagnostic and therapeutic
      decisions.
AB  - PURPOSE: To assess the effect of knee magnetic resonance (MR) imaging on the
      diagnosis and management of acute knee injury. MATERIALS AND METHODS: Two
      orthopedic knee surgeons prospectively completed pre- and post-MR imaging
      questionnaires on 84 of 91 consecutive patients with acute knee injury. The pre-
      and post-MR imaging clinical diagnoses, certainty regarding these diagnoses,
      other diagnostic tests, and subjective impression of the usefulness of MR imaging
      were determined. RESULTS: Seven hundred thirty-one of 840 pre- and post-MR
      imaging diagnoses agreed. Agreement was lowest for medial meniscal injuries (54
      of 84). Significantly fewer meniscal injuries were suspected after MR imaging (P
      < .05). In 60 patients, the orthopedist changed at least one of the 10 potential
      diagnoses after MR imaging. Clinical diagnostic certainty increased by a mean of
      14% for all diagnoses. The increase in diagnostic certainty was greatest for
      medial meniscal injuries (30%), followed by lateral meniscal injuries (21%). The
      proposed management changed in 41 patients, resulting in significantly fewer
      arthroscopic procedures (P < .01). The post-MR imaging management plans included
      37% (27 of 73) fewer arthroscopic procedures. CONCLUSION: MR imaging affects the
      diagnosis and management of acute knee injury by decreasing the number of
      arthroscopic procedures, improving clinician diagnostic certainty, and assisting
      in management decisions.

PMID- 9280266
TI  - Acute cervical spine trauma: diagnostic performance of single-view versus three
      view radiographic screening.
AB  - PURPOSE: To compare the diagnostic accuracy of single-view and three-view
      cervical spine radiographs in acute trauma. MATERIALS AND METHODS: Radiographs of
      97 patients with acute cervical spine fractures were matched with those of 92
      proved normal cases. Fourteen radiologists, including three senior attending
      radiologists each with more than 20 years of post-residency experience, four
      junior attending radiologists each with less than 5 years of practice experience,
      three senior radiology residents in their 3rd or 4th year of radiology residency,
      and four junior radiology residents at the end of their 1st year of radiology
      training, interpreted each case twice: once as a lateral-only study and again as
      a three-view study. Multireader-multicase receiver operating characteristic
      analysis was performed. Difficult cases were reviewed for trends in the errors.
      RESULTS: Eight of 14 readers detected fractures better with the three-view
      series. Among junior attending radiologists, the differences were statistically
      significant. Most improvements were in fractures of the dens and fractures and
      unilateral dislocations of the articular mass. Overall, sensitivity increased
      from 81.8% to 83.3%. The reliability of fracture classification improved. Less
      experienced readers performed better with the three-view series. CONCLUSION: A
      three-view screening radiographic series will allow most readers to detect a few
      more fractures than a single-view series. The improvements occur primarily in a
      subset of difficult-to-diagnose injuries.

PMID- 9280265
TI  - Early chronic lymphocytic leukemia: prognostic value of quantitative bone marrow
      MR imaging findings and correlation with hematologic variables.
AB  - PURPOSE: To determine the frequency of abnormal findings from quantitative bone
      marrow magnetic resonance (MR) imaging in patients with early-stage chronic
      lymphocytic leukemia, to correlate these findings with clinical parameters, and
      to compare spontaneous outcome in patients with normal or abnormal MR imaging
      findings. MATERIALS AND METHODS: In 21 patients with Binet stage A (Rai stage 0
      I) disease, bulk T1 values of the vertebral bone marrow were determined and
      correlated with initial clinical, laboratory, histopathologic, and cytogenetic
      findings and with treatment-free survival. RESULTS: Bulk T1 values were normal (<
      600 msec) in 14 patients and prolonged in seven. Patients with increased T1 had
      significantly higher blood (P = .017) and bone marrow (P = .015) lymphocytosis.
      None of the 14 patients with normal T1 values required specific therapy after a
      median follow-up of 13 months. Of the seven patients with abnormal T1 values,
      five required treatment after progression to Binet stage B or C disease at a
      median of 10 months. CONCLUSION: In patients with abnormal quantitative MR
      imaging findings, treatment-free survival appears to be significantly shorter (P
      < .001) than in patients with normal MR imaging findings.

PMID- 9280267
TI  - Arthritic temporomandibular joint: correlation of macromolecular contrast
      enhanced MR imaging parameters and histopathologic findings.
AB  - PURPOSE: To assess the utility of macromolecular contrast material-enhanced
      magnetic resonance (MR) imaging parameters for determining the histopathologic
      severity of temporomandibular joint (TMJ) arthritis. MATERIALS AND METHODS:
      Ovalbumin was used to induce arthritis in the TMJs of 10 previously sensitized
      adult white rabbits. Five rabbits composed the sham-treated control group.
      Dynamic spin-echo imaging was performed immediately before and for 30 minutes
      after injection of macromolecular contrast medium. Histologic specimens of TMJ
      were assessed quantitatively for arthritis. Changes in MR signal intensity were
      derived from the synovial and subsynovial tissues of the TMJ, and plasma volume
      (PV) and permeability surface area product (PS) were calculated. These MR
      parameters and the arthritic scores were compared between sham-treated and
      antigen-challenged TMJs. The relationships between MR parameters and
      histopathologic indexes were also determined. RESULTS: Arthritic TMJs showed
      marked enhancement of the synovial and subsynovial tissues over the imaging
      period. PS and all histopathologic indexes of arthritis were significantly
      greater (P < .005) in antigen-challenged than in sham-treated TMJs. PS
      demonstrated strong positive relationships with all histologic parameters of
      arthritis, indicating its utility for assessing the severity of joint
      inflammation. CONCLUSION: Macromolecular contrast-enhanced MR imaging enables
      quantification of PS and PV in inflamed joints. This technique may provide
      insights into the pathogenesis of joint inflammation and noninvasive monitoring
      of disease severity and treatment response in arthritis.

PMID- 9280269
TI  - Postoperative changes in the brain: MR imaging findings in patients without
      neoplasms.
AB  - PURPOSE: To determine the time course of postoperative changes in the brain by
      using magnetic resonance (MR) imaging. MATERIALS AND METHODS: Contrast material
      enhanced MR images (32 preoperative, 161 postoperative) in 95 patients who
      underwent temporal lobectomy for treatment of nonneoplastic epilepsy were
      evaluated for enhancement pattern at the surgical margin and for the presence of
      dural enhancement, fluid, and air. Images were obtained 9 hours to 5.6 years
      after surgery. RESULTS: Surgical margin contrast enhancement was present and
      increased from 20 hours to 29 days after surgery. The predominant early (days 0
      5) pattern was thin linear enhancement (16 of 18 [89%] images). The later (days 6
      29) pattern was thick linear or nodular (tumorlike appearance) (11 of 18 [61%]
      images). Surgical margin enhancement was absent after day 30, although few data
      were collected 1-5 months after surgery. Dural enhancement was seen on 96 of 97
      (99%) postoperative MR images. Extraaxial fluid was seen on all 46 images
      obtained during the first 30 days and was absent by day 51. Intracranial air was
      present on 31 of 35 (89%) images obtained during the first 4 days but was absent
      after day 5. CONCLUSION: Knowledge of the evolution of contrast enhancement
      patterns on postoperative MR images of the brain can help in differentiating
      benign from neoplastic changes.

PMID- 9280268
TI  - Functional MR imaging during odor stimulation: preliminary data.
AB  - PURPOSE: To determine the locations and extent of activation in areas of the
      brain at functional magnetic resonance (MR) imaging with olfactory stimulation
      and to determine whether accommodation or amplification of brain activation
      occurs with sequential olfactory stimulation. MATERIALS AND METHODS: Five adult
      men with normal senses of smell underwent multisection, gradient-echo, echo
      planar imaging according to a blood-oxygen-level-dependent experimental paradigm.
      Odorants that nearly exclusively stimulate the olfactory system and odorants that
      stimulate the olfactory and trigeminal nerves were compared by using repetitive
      imaging procedures. RESULTS: Activation with olfactory nerve-mediated odorants
      was demonstrated in the orbitofrontal cortex (Brodmann area 11) with a right
      sided predominance. Mild cerebellar stimulation was also observed. With repeated
      testing, overall activation with olfactory nerve-mediated odorants declined.
      Odorants that also stimulated the trigeminal nerve produced additional cingulate,
      temporal, cerebellar, and occipital activation. Activation with combined
      trigeminal and olfactory system odors increased more than sixfold with repeated
      testing. CONCLUSION: Olfactory nerve-mediated and combined olfactory and
      trigeminal nerve-mediated odorants activate different regions of the brain.
      Orbitofrontal stimulation spreads to all parts of the brain when a trigeminal
      component is added. Habituation (deactivation) occurs with repeated testing of
      olfactory nerve-mediated odorants, while, paradoxically, activation increases
      with repeated exposure to odors that also stimulate the trigeminal nerve.

PMID- 9280270
TI  - Degeneration of the ipsilateral substantia nigra after striatal infarction:
      evaluation with MR imaging.
AB  - PURPOSE: To evaluate the degeneration of the ipsilateral substantia nigra after
      striatal infarction by using magnetic resonance (MR) imaging. MATERIALS AND
      METHODS: Twenty-five adult patients with embolic cerebral infarction of the
      middle cerebral artery distribution underwent MR imaging 0-4, 5-9, 12-15, and 27
      29 days after the stroke. Sixteen of them also underwent follow-up MR imaging 2
      12 months after the stroke. RESULTS: Ten patients had an infarct in the striatum
      with or without a cortical infarct (striatal infarction group); the other 15
      patients had an infarct in the cerebral cortex of the middle cerebral artery
      distribution without a striatal infarct (cortical infarction group). In all 10
      patients with striatal infarction, a hyperintense spot appeared in the
      ipsilateral substantia nigra on T2-weighted fast spin-echo images 7-12 days after
      the onset. This area became less intense and smaller 3 months later. In the
      cortical infarction group, no hyperintense spot in the ipsilateral substantia
      nigra was observed at any time. CONCLUSION: Degeneration of the substantia nigra
      ipsilateral to the striatal infarction was clearly demonstrated at MR imaging.
      This finding should not be mistaken for further cerebral infarction.

PMID- 9280271
TI  - Pseudarthrosis: US evaluation after posterolateral spinal fusion: work in
      progress.
AB  - PURPOSE: To determine the value of ultrasound (US) in evaluation of
      pseudarthrosis after posterolateral spinal fusion. MATERIALS AND METHODS: In 10
      patients who had undergone bilateral posterolateral thoracic or lumbar fusion
      with autologous bone graft and instrumentation more than 9 months previously, US
      was performed within 1 week before second-look surgery. A total of 20 sites each
      side of midline were evaluated for the presence of bone graft, solid fusion,
      clefts, fluid collections, and hardware visibility. US findings were compared
      with those at surgery. In three patients, standard radiographs were reviewed
      before US; blinded US evaluation was performed in the remaining seven patients.
      RESULTS: At US, all 10 sites of pseudarthrosis seen at surgery were identified
      correctly. Of 10 sites with solid fusion at surgery, US depicted six. At four
      sites (two patients), fusion was mistaken for or obscured by hardware. Overall,
      sensitivity was 100%, specificity was 60%, and accuracy was 80%. CONCLUSION: US
      can play a valuable role in the detection of posterolateral bone graft
      pseudarthrosis, especially when hardware is present.

PMID- 9280272
TI  - Invasive thymoma: treatment with postoperative radiation therapy.
AB  - PURPOSE: To assess radiation therapy and chemotherapy in the treatment of
      invasive thymoma and thymic carcinoma. MATERIALS AND METHODS: In 1981-1995, 43
      patients received irradiation after total (n = 23) or subtotal (n = 20)
      resection. Tumors were thymic carcinoma (n = 10) or invasive thymoma (n = 33).
      Masaoka stage was II in 10 patients, III in 14, and IV in 19. Median total dose
      applied was 50 Gy (range, 10-72 Gy). Seventeen patients (five with stage III and
      12 with stage IV) also received chemotherapy. RESULTS: Patients with thymic
      carcinoma had a median survival of 9.5 months, compared with 50 months for
      patients with invasive thymoma (P = .008). Patients' median survival and 5-year
      survival rates were 97 months and 90% for stage II, 65 months and 67% for stage
      III, and 32.5 months and 30% for stage IV tumors (P = .024). Overall control rate
      within the radiation field was 81% (35 patients) and overall local control rate
      within the thorax was 74% (32 patients). Of the 17 patients who received
      chemotherapy and radiation therapy, nine had thymic carcinoma and a median
      survival of 12 months (range, 1.4-23.0 months). CONCLUSION: With total doses of
      45-50 Gy, local control is achievable after radical resection. Whether patients
      with completely resected stage II thymomas should receive radiation after surgery
      remains uncertain, as does the role of chemotherapy in the treatment of thymoma.

PMID- 9280273
TI  - Superior vena cava stents: Doppler US of the internal mammary veins to detect
      collateral flow--preliminary observations.
AB  - In 12 patients with superior vena cava syndrome secondary to malignant disease,
      duplex Doppler ultrasound (US) was performed in the internal mammary veins. In
      all patients, flow was retrograde. After stent placement, flow direction was
      again antegrade on one side (17%) or both sides (83%). During follow-up in the
      internal mammary veins, blood flow remained unchanged in 10 patients and
      retrograde flow recurred in two patients at 2 and 5 months, respectively. In
      these two patients, helical computed tomography showed stent failure. Successful
      treatment in one patient normalized the direction of flow in the internal mammary
      vein. Doppler US in the internal mammary veins allowed accurate evaluation of
      function of superior vena cava stents.

PMID- 9280274
TI  - Hemodynamic imaging with pulsatility-index and resistive-index color Doppler US.
AB  - Pulsatility index and resistive index were mapped with color Doppler ultrasound
      (US) and compared with spectral Doppler US findings. In the carotid arteries
      and/or kidneys in 12 healthy subjects, the pulsatility index and resistive index
      were estimated from mean frequency shifts and mapped into "cool-warm" or
      "rainbow" color scales. Surveys that depicted intervessel variations in a complex
      vascular field were useful in deciding where to perform spectral Doppler US.
      Intravessel variations were consistent with fluid dynamic theory.

PMID- 9280275
TI  - Umbilical vein nomenclature.

PMID- 9280276
TI  - Meniscal flounce or buckling.

PMID- 9280277
TI  - Uveal melanoma.

PMID- 9280278
TI  - Control of massive hemoptysis due to pulmonary tuberculosis with bronchial
      arterial embolization.

PMID- 9280279
TI  - Drosophila alcohol dehydrogenase: evaluation of Ser139 site-directed mutants.
AB  - Drosophila alcohol dehydrogenase (DADH) belongs to the large and highly
      heterogeneous (15-30% residue identity) short-chain dehydrogenase/reductase
      family (SDR). It is the only reported member that oxidizes mainly ethanol and 2
      propanol among other alcohols. To confirm the role of Ser139 we constructed two
      site-directed mutants, Ser139Ala and Ser139Cys, which show no enzymatic activity.
      Molecular replacement and data from crystallographically refined 3D structures
      confirm the position of Ser139, whose hydroxyl group faces the cleft of the
      presumed catalytic pocket, very close to Tyr152 and Lys156. Thus, consistent with
      the constitution of the catalytic triad of other SDR, our results suggest that
      Ser139 of DADH is directly involved in the catalytic reaction.

PMID- 9280280
TI  - Unexpected influence of a C-terminal-fused His-tag on the processing of an enzyme
      and on the kinetic and folding parameters.
AB  - The addition of a poly-His C-terminal extension, designed to facilitate the
      purification of the protein, to the beta-lactamase of a thermophilic Bacillus
      licheniformis strain modified the site of action of the signal peptidase. This
      resulted in the secretion of a protein with a different N-terminus, showing that
      this type of protein engineering might not always be as 'neutral' as generally
      assumed.

PMID- 9280281
TI  - Vinculin gene is non-essential in Drosophila melanogaster.
AB  - Vinculin is thought to be an important cytoskeletal protein in the linkage
      between actin cytoskeleton and integrin transmembrane receptors. We identified
      Vinculin (Vinc) gene in the X chromosome of D. melanogaster. Drosophila vinculin
      is highly homologous in its N- and C-terminal domains both to mammalian and
      nematode vinculins, and contains internal repeats and proline-rich region typical
      for vinculins. The X chromosome rearrangement In(1LR)pn2a was found to disrupt
      Vinc so that the coding sequence is interrupted by the (AAGAG)n satellite DNA.
      Northern analysis revealed that the Vinc transcript is completely absent in the
      In(1LR)pn2a homozygous flies. Surprisingly, these Vinc flies are viable and
      fertile. This finding highlights plasticity and adaptive capacity of cellular
      cytoskeletal and anchorage system.

PMID- 9280282
TI  - Possible involvement of radical reactions in desialylation of LDL.
AB  - The role of oxidatively modified LDL in the pathogenesis of atherosclerosis has
      been well documented. These studies have focused on modifications of lipid and
      protein parts of LDL. Recently desialylated LDL has received attention in
      relation to atherosclerosis and coronary artery disease. We examined the possible
      involvement of radical reactions in desialylation of LDL. Human LDL was subjected
      to oxidative damage using Cu2+ ion. As the conjugated dienes monitored by
      absorption at 234 nm increased, the content of sialic acid decreased steadily.
      Both the elevation of conjugated diene and the decrease of sialic acid were
      inhibited by beta-mercaptoethanol, a typical radical scavenger. Besides, both
      butylated hydroxytoluene and a nitrogen atmosphere inhibited the decrease of
      sialic acid. These inhibition experiments suggested that sialic acid moieties in
      LDL were reactive toward radicals.

PMID- 9280284
TI  - Mutational analysis eliminates Glu64 and Glu94 as candidates for 'catalytic
      carboxylate' in the bacterial ATP-binding-cassette protein MalK.
AB  - MalK is the ATP-hydrolyzing subunit of the binding protein-dependent ATP-binding
      cassette (ABC) transport system for maltose from Salmonella typhimurium. In a
      recent hypothesis, Glu64 and Glu94 of MalK were proposed as candidates for
      'catalytic carboxylate', common to ATP- and GTP-hydrolyzing proteins [Yoshida and
      Amano (1995) FEBS Lett. 359, 1-5]. Substitution of both residues and,
      additionally, Glu74 by either glutamine or glycine and valine, respectively, had
      no deleterious effect on maltose transport. Thus, our data disprove the above
      notion.

PMID- 9280285
TI  - Sequence of two gonadotropin releasing hormones from tunicate suggest an
      important role of conformation in receptor activation.
AB  - The primary structure of two forms of gonadotropin releasing hormone (GnRH) from
      tunicate (Chelyosoma productum) have been determined based on mass spectrometric
      and chemical sequence analyses. The peptides, tunicate GnRH-I and -II, contain
      features unprecedented in vertebrate GnRH. Tunicate GnRH-I contains a putative
      salt bridge between Asp5 and Lys8. A GnRH analog containing a lactam bridge
      between Asp5 and Lys8 was found to increase release of estradiol compared with
      that of the native tunicate GnRH-I and -II. Tunicate GnRH-II contains a cysteine
      residue and was isolated as a dimeric peptide. These motifs suggest that the
      conformation plays an important role in receptor activation.

PMID- 9280283
TI  - Missense mutations affecting a conserved cysteine pair in the TH domain of Btk.
AB  - Tec family protein tyrosine kinases have in their N-terminus two domains. The PH
      domain is followed by Tec homology (TH) domain, which consists of two motifs. The
      first pattern, Btk motif, is also present in some Ras GAP molecules. C-terminal
      half of the TH domain, a proline-rich region, has been shown to bind to SH3
      domains. Mutations in Bruton's tyrosine kinase (Btk) belonging to the Tec family
      cause X-linked agammaglobulinemia (XLA) due to developmental arrest of B cells.
      Here we present the first missense mutations in the TH domain. The substitutions
      affect a conserved pair of cysteines, residues 154 and 155, involved in Zn2+
      binding and thereby the mutations alter protein folding and stability.

PMID- 9280287
TI  - Natural hidden antibodies reacting with DNA or cardiolipin bind to thymocytes and
      evoke their death.
AB  - Both free and hidden natural antibodies to DNA or cardiolipin were obtained from
      immunoglobulins of a normal donor. The free antibodies reacting with DNA or
      cardiolipin were isolated by means of affinity chromatography. Antibodies
      occurring in an hidden state were disengaged from the depleted immunoglobulins by
      ion-exchange chromatography and were then affinity-isolated on DNA or cardiolipin
      sorbents. We used flow cytometry to study the ability of free and hidden
      antibodies to bind to rat thymocytes. Simultaneously, plasma membrane integrity
      was tested by propidium iodide (PI) exclusion. The hidden antibodies reacted with
      65.2 +/- 10.9% of the thymocytes and caused a fast plasma membrane disruption.
      Cells (28.7 +/- 7.1%) were stained with PI after incubation with the hidden
      antibodies for 1 h. The free antibodies bound to a very small fraction of the
      thymocytes and did not evoke death as compared to control without antibodies. The
      possible reason for the observed effects is difference in reactivity of the free
      and hidden antibodies to phospholipids. While free antibodies reacted
      preferentially with phosphotidylcholine, hidden antibodies reacted with
      cardiolipin and phosphotidylserine.

PMID- 9280286
TI  - Isolation and characterization of mutations affecting expression of the delta9-
      fatty acid desaturase gene, OLE1, in Saccharomyces cerevisiae.
AB  - Expression of the delta9- fatty acid desaturase gene, OLE1, of Saccharomyces
      cerevisiae is negatively regulated transcriptionally and post-transcriptionally
      by unsaturated fatty acids. In order to isolate mutants exhibiting irregulation
      of OLE1 expression, we constructed an OLE1p-PHO5 fusion gene as a reporter
      consisting of the PHO5 gene encoding repressible acid phosphatase (rAPase) under
      the control of the OLE1 promoter (OLE1p). By EMS mutagenesis, we isolated three
      classes of mutants, pfo1, pfo2 and pfo3 positive regulatory factor for OLE1)
      mutants, which show decreased rAPase activity under derepression conditions
      (absence of oleic acid). Analysis of the transcription of OLE1 in these pfo
      mutants revealed that pfo1 and pfo3 mutants have a defect in the regulation of
      OLE1 expression at the transcriptional level while pfo2 mutants were suggested to
      have a mutation affecting OLE1 expression at a post-transcriptional step. In
      addition, four other classes of mutants, nfo1, nfo2, nfo3 and nfo4 (negative
      factor for OLE1) mutants that have mutations causing strong expression of the
      OLE1p-PHO5 fusion gene under repression conditions (presence of oleic acid), were
      isolated. Results of Northern analysis of OLE1 as well as OLE1p-PHO5 transcripts
      in nfo mutants suggested that these mutations occurred in genes encoding global
      repressors. We also demonstrated that TUP1 and SSN6 gene products are required
      for full repression of OLE1 gene expression, by showing that either tup1 or ssn6
      mutations greatly increase the level of the OLE1 transcript.

PMID- 9280288
TI  - Peroxynitrite-induced hemolysis of human erythrocytes and its inhibition by
      antioxidants.
AB  - It was found that human erythrocytes underwent hemolysis when incubated with
      peroxynitrite at 37 degrees C under air. The extent of hemolysis increased with
      increasing peroxynitrite concentration and decreasing hematocrit. The
      peroxynitrite-induced hemolysis was suppressed only partially by a radical
      scavenging antioxidant such as uric acid and Trolox, a water-soluble vitamin E
      analogue, but reduced glutathione, N-acetylcysteine and albumin efficiently
      inhibited the hemolysis. A selenium-containing organic compound, ebselen, also
      suppressed the hemolysis. On the other hand, nitric oxide and superoxide
      generated concomitantly from 3-morpholinosydnonimine (SIN-1) did not induce
      appreciable hemolysis, while it converted hemoglobin to methemoglobin
      extensively.

PMID- 9280289
TI  - Singlet oxygen is an early intermediate in cytokine-dependent ultraviolet-A
      induction of interstitial collagenase in human dermal fibroblasts in vitro.
AB  - Ultraviolet (UV) A irradiation of human dermal fibroblasts elicits an increase in
      specific mRNA amounts and bioactivities of the cytokines IL-1alpha, IL-1beta, and
      IL-6. These effects are enhanced in deuterium oxide-based medium and are
      diminished in the presence of non-toxic concentrations of sodium azide.
      Furthermore, generating singlet oxygen outside the cells by irradiation of rose
      bengal-coated resin particles with visible light (lambda > 450 nm) results in the
      induction of interstitial collagenase, IL-1 and IL-6, similar to the response
      observed with UVA irradiation. These observations suggest that singlet oxygen is
      an early intermediate in the signaling pathway of IL-1 and IL-6 mediating UVA
      induction of interstitial collagenase (E.C. 3.4.24.7). Furthermore, singlet
      oxygen appears to initiate this complex UV response at the cell membrane.

PMID- 9280290
TI  - Molecular characterization of a novel human PDZ domain protein with homology to
      INAD from Drosophila melanogaster.
AB  - PDZ domains are thought to act as protein-binding modules mediating the
      clustering of membrane and membrane-associated proteins. The INAD protein has
      been shown to interact via a PDZ domain with the calcium channel TRP which
      contributes to capacitative calcium entry into Drosophila photoreceptor cells. We
      have cloned the cDNA of a human INAD-Like protein (hINADL) of 1524 amino acids in
      length containing at least five PDZ domains. Additionally, two truncated versions
      hINADL(delta304) and hINADL(delta853) were identified. hInadl transcripts of
      differing size are expressed in various tissues including brain, where
      transcripts are abundant in the cerebellum.

PMID- 9280291
TI  - Detection of secretory phospholipase A2s related but not identical to type IIA
      isozyme in cultured mast cells.
AB  - We previously reported that BALB/cJ mouse-derived bone marrow-derived mast cells
      (BMMC) exhibited two sequential phases of prostaglandin D2 (PGD2) generation in
      response to Fc(epsilon) receptor I (Fc(epsilon)RI) crosslinking and cytokine
      stimulation, the late phase of which was suppressed by an antibody raised against
      type IIA secretory phospholipase A2 (sPLA2). Here we report that BMMC derived
      from C57BL/6J mice, which are genetically deficient in type IIA sPLA2, display
      both immediate and delayed PGD2 generation normally. Lysates of C57BL/6J-derived
      BMMC contained a Ca2+-dependent PLA2 that was absorbed to a column conjugated
      with anti-type IIA sPLA2 antibody and had a similar molecular mass of 14 kDa, as
      assessed by immunoblotting. Therefore we speculate that a sPLA2 similar to, but
      distinct from, type IIA sPLA2 would compensate for type IIA sPLA2 deficiency in
      C57BL/6J-derived BMMC. We found that the two type IIA-related sPLA2 family
      members, type V and type IIC sPLA2s, were expressed in BMMC as well as in rat
      mastocytoma RBL-2H3 cells.

PMID- 9280292
TI  - Glycoprotein VI is the collagen receptor in platelets which underlies tyrosine
      phosphorylation of the Fc receptor gamma-chain.
AB  - We have recently shown that collagen activates platelets through a pathway
      dependent on the Fc receptor gamma-chain and the tyrosine kinase Syk. We report
      here that the Fc receptor gamma-chain and the candidate collagen receptor
      glycoprotein VI (GPVI) co-associate. Furthermore, cross-linking GPVI stimulates a
      similar pattern of tyrosine phosphorylation to that stimulated by collagen,
      including tyrosine phosphorylation of Fc receptor gamma-chain. These results
      support a model where GPVI couples collagen-stimulation of platelets to
      phosphorylation of the Fc receptor gamma-chain leading to activation of Syk and
      phospholipase Cgamma2.

PMID- 9280293
TI  - Identification of a 48-kDa prenylated protein that associates with microtubules
      as 2',3'-cyclic nucleotide 3'-phosphodiesterase in FRTL-5 cells.
AB  - In an effort to study the nature of tubulin attachment to membranes, we have
      previously observed that after blocking prenylation in FRTL-5 thyroid cells, the
      microtubules become disconnected from the plasma membrane region [Bifulco M. et
      al. (1983) J. Cell. Physiol. 155, 340-348]. In this study we show that several
      [3H]mevalonate labeled proteins in FRTL-5 cells associate with membrane and
      cytoskeleton and, among these, we describe the presence of a 48-kDa prenylated
      protein, identified by immunoprecipitation as 2',3'-cyclic nucleotide 3'
      phosphodiesterase (CNP), that associates with microtubules. This latter
      association persists through several polymerization/depolymerization cycles,
      whereas other prenylated proteins are lost. It is suggested that CNP can be a
      novel microtubule-associated protein (MAP) and a promising candidate as a
      membrane anchor for microtubules.

PMID- 9280294
TI  - The use of recombinant vaccinia virus to generate monoclonal antibodies against
      the cell-surface glycoprotein endoglin.
AB  - Characterization of novel cell-surface protein molecules, initially identified by
      cDNA cloning techniques, usually requires the generation of specific antibodies
      to further analyze their biochemical and/or functional properties. Here we report
      a simple method, using recombinant vaccinia virus, for the generation of
      monoclonal antibodies (mAb) to the cell-surface antigen endoglin. A recombinant
      vaccinia virus carrying a cDNA encoding human endoglin was inserted into the
      thymidine kinase locus under the control of the 7.5k vaccinia virus promoter.
      Infection of Balb/c mice with this recombinant virus led to the generation of
      specific polyclonal antibodies, as demonstrated by the antisera reactivity
      against human endoglin transfectants. The spleen cells of these infected animals
      were fused to myeloma cells, allowing efficient generation of several hybridomas
      which secrete mAbs to human endoglin, as evidenced by their reactivity with
      purified endoglin as well as with endoglin transfectants. Some of the mAbs
      selected seem to be specific for regions of endoglin conserved among different
      species as evidenced by their cross-reactivity with chicken endoglin. These
      results underline the utility of recombinant vaccinia virus to generate
      antibodies with novel properties to new cell surface proteins such as endoglin.

PMID- 9280295
TI  - Nitric oxide inhibits enterocyte mitochondrial phospholipase D.
AB  - Mitochondrial damage is one of the prominent features of cell death in oxidative
      stress and related pathological conditions. Alteration in membrane lipid
      composition may be responsible for the mitochondrial damage. In this study, we
      have shown that intestinal mitochondria contain an active phospholipase D (PLD)
      which is activated by oxidants, Ca2+ or polyamines and this results in
      degradation of phosphatidylethanolamine (PE) and formation of phosphatidic acid
      (PA). This PLD activity is inhibited by nitric oxide (NO) which prevents the
      lipid alteration in mitochondria when exposed to these agents. This can be
      reversed by the NO scavenger, haemoglobin. This suggests that alteration of
      mitochondrial membrane lipid composition by activation of PLD in certain
      pathological condition such as oxidative stress may be prevented by the
      simultaneous presence of nitric oxide.

PMID- 9280296
TI  - The 14-3-3 protein binds its target proteins with a common site located towards
      the C-terminus.
AB  - The 14-3-3 protein family binds a variety of proteins in cell-signaling pathways,
      but the structural elements necessary for the ligand binding are poorly
      understood. Here we demonstrate that the 'box-1' region, which spans residues 171
      213 in the eta-isoform and was previously identified as the binding site of 14-3
      3 to the phosphorylated tryptophan hydroxylase, plays a critical role in the
      interaction with many target proteins. Using a series of truncated 14-3-3
      mutants, we show that the mutant 167-213 carrying box-1 binds bacurovirus
      expressed Raf-1 and Bcr protein kinases to the similar extent as the full-length
      14-3-3 in a phosphorylation-dependent manner, while the mutants lacking this
      region abolish the binding activity. Furthermore, the box-1 region also appears
      essential for binding of 14-3-3 to more than 40 phosphoproteins found in the
      brainstem extract. These results suggest that the box-1 region, consisting of
      helices 7 and 8 in the tertiary structure, is a common structural element whereby
      the 14-3-3 protein binds many, if not all, target proteins.

PMID- 9280298
TI  - NMR characterization of the full-length recombinant murine prion protein, mPrP(23
      231).
AB  - The recombinant murine prion protein, mPrP(23-231), was expressed in E. coli with
      uniform 15N-labeling. NMR experiments showed that the previously determined
      globular three-dimensional structure of the C-terminal domain mPrP(121-231) is
      preserved in the intact protein, and that the N-terminal polypeptide segment 23
      120 is flexibly disordered. This structural information is based on nearly
      complete sequence-specific assignments for the backbone amide nitrogens, amide
      protons and alpha-protols of the polypeptide segment of residues 121-231 in
      mPrP(23-231). Coincidence of corresponding sequential and medium-range nuclear
      Overhauser effects (NOE) showed that the helical secondary structures previously
      identified in mPrP(121-231) are also present in mPrP(23-231), and near-identity
      of corresponding amide nitrogen and amide proton chemical shifts indicates that
      the three-dimensional fold of mPrP(121-231) is also preserved in the intact
      protein. The linewidths in heteronuclear 1H-15N correlation spectra and 15N[1H]
      NOEs showed that the well structured residues 126-230 have correlation times of
      several nanoseconds, as is typical for small globular proteins, whereas
      correlation times shorter than 1 nanosecond were observed for all residues of
      mPrP(23-231) outside of this domain.

PMID- 9280297
TI  - Recombinant full-length murine prion protein, mPrP(23-231): purification and
      spectroscopic characterization.
AB  - The cellular prion protein of the mouse, mPrP(C), consists of 208 amino acids
      (residues 23-231). It contains a carboxy-terminal domain, mPrP(121-231), which
      represents an autonomous folding unit with three alpha-helices and a two-stranded
      antiparallel beta-sheet. We expressed the complete amino acid sequence of the
      prion protein, mPrP(23-231), in the cytoplasm of Escherichia coli. mPrP(23-231)
      was solubilized from inclusion bodies by 8 M urea, oxidatively refolded and
      purified to homogeneity by conventional chromatographic techniques. Comparison of
      near-UV circular dichroism, fluorescence and one-dimensional 1H-NMR spectra of
      mPrP(23-231) and mPrP(121-231) shows that the amino-terminal segment 23-120,
      which includes the five characteristic octapeptide repeats, does not contribute
      measurably to the manifestation of three-dimensional structure as detected by
      these techniques, indicating that the residues 121-231 might be the only
      polypeptide segment of PrP(C) with a defined three-dimensional structure.

PMID- 9280299
TI  - Antioxidant role of melatonin in lipid peroxidation of human LDL.
AB  - The antioxidant effect of melatonin on LDL oxidation was studied in vitro using
      either a thermolabile initiator or copper ions to induce lipid peroxidation.
      Loading of LDL with melatonin showed only weak protection against oxidative
      damage as compared to alpha-tocopherol. In the presence of high concentrations of
      melatonin (1000 mol/mol LDL) in the medium a clear protective effect was found
      during lag- and propagation phase, albeit weaker than after loading with alpha
      tocopherol. It is concluded that melatonin is not incorporated into LDL in
      sufficient concentrations to prevent lipid peroxidation effectively. When
      melatonin is present in the incubation medium during oxidation, a partitioning
      equilibrium between aqueous and lipid phase is established. Only under these
      conditions can melatonin act as a chain breaking antioxidant. The concentrations
      required, however, are far beyond those found in human plasma. Therefore, the
      data in this study do not support a direct physiological relevance of melatonin
      as an antioxidant in lipid peroxidation processes.

PMID- 9280301
TI  - An AU at the first base pair of helix 3 elevates the catalytic activity of
      hepatitis delta virus ribozymes.
AB  - A mutational analysis of the helix 3 (H3) region of hepatitis delta virus (HDV)
      ribozymes disclosed that an AU at the first base pair of H3 elevates the
      catalytic activity of various cis- and trans-acting HDV ribozymes. A GC to AU
      substitution at this position of H3, which is located at the junction of three of
      the four helices of the pseudoknot-like structure model, altered the structure of
      HDV ribozymes. This substitution in the H3 did not change the independence of the
      cleavage rate to pH nor the sensitivity to formamide treatment of the ribozymes.

PMID- 9280300
TI  - Over-expression of plant 14-3-3 proteins in tobacco: enhancement of the
      plasmalemma K+ conductance of mesophyll cells.
AB  - Two cDNA clones encoding 14-3-3 homologous proteins were isolated from Vicia
      faba. Deduced amino acid sequences share different degrees of homology with other
      plant 14-3-3 proteins. Both clones, under the control of the CaMV 35S promoter,
      were transformed into tobacco plants. Immunoblotting showed three different forms
      of ca. 31, 34, and 37 kDa, indicating a covalent modification of the expressed 14
      3-3 proteins. These forms were mainly present in the microsomal fraction. Patch
      clamp studies of mesophyll protoplasts of the transformants revealed a strongly
      enhanced K+ conductance compared to the wild type. This indicates the involvement
      of 14-3-3 proteins in ion channel regulation, presumably by modulating kinase
      activities or binding the channel.

PMID- 9280302
TI  - Impaired expression of transcription factor IUF1 in a pancreatic beta-cell line
      derived from a patient with persistent hyperinsulinaemic hypoglycaemia of infancy
      (nesidioblastosis).
AB  - Persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI), or
      nesidioblastosis, is a rare disorder which may be familial or sporadic, and which
      is characterized by unregulated secretion of insulin and profound hypoglycaemia
      in the neonate. The defect has been linked in some patients to mutations in the
      sulphonyl urea receptor gene (SUR). The present study investigated potential
      defects in the regulation of the insulin gene by glucose in a beta-cell line (NES
      2Y) derived from a patient with PHHI. The results show that the insulin promoter
      is unresponsive to glucose in PHHI, and that this defect can be attributed to
      impaired expression of the transcription factor IUF1. Because IUF1 is involved
      not only in linking glucose metabolism to the control of the insulin, but is also
      a major regulator of beta-cell differentiation during embryogenesis, we propose
      that impaired expression of IUF1 contributes to beta-cell dysfunction in PHHI by
      leading to abnormal beta-cell differentiation.

PMID- 9280303
TI  - Characterization of three cDNA species encoding plastid RNA polymerase sigma
      factors in Arabidopsis thaliana: evidence for the sigma factor heterogeneity in
      higher plant plastids.
AB  - By database search analysis, we identified three Arabidopsis EST (Expression
      Sequence Tag) entries having similarity to eubacterial RNA polymerase sigma
      factors. cDNA clones corresponding to these partial sequences were isolated, and
      the complete nucleotide sequences were determined. All three sequences encode
      proteins highly homologous to cyanobacterial and plastid sigma factors, and the
      gene products have N-terminal extensions which are assumed to function as plastid
      targeting transit peptides. Thus we have concluded that the gene products are RNA
      polymerase sigma factors of plastids, and named sigA, sigB and sigC,
      respectively. Expression of these genes was analyzed by RNA gel-blot analysis and
      shown to be induced by illumination after a short-term dark adaptation. This
      strongly suggests that light regulation of the nuclear encoded sigma factor genes
      is involved in light-dependent activation of plastid promoters.

PMID- 9280304
TI  - Prostaglandin E2 synthesis is differentially affected by reactive nitrogen
      intermediates in cultured rat microglia and RAW 264.7 cells.
AB  - We studied the effects of nitric oxide (NO) on prostanoid production,
      cyclooxygenase (COX-2) expression and [3H]arachidonic acid (AA) release in RAW
      264.7 macrophagic cells and rat microglial primary cultures. Inhibition of NO
      synthesis enhanced microglial prostanoid production without affecting that of RAW
      264.7 cells. Both 3-morpholinosydnonimine (SIN-1), (which, by releasing NO and
      superoxide, leads to the formation of peroxynitrite), and S-nitroso-N
      acetylpenicillamine (SNAP), (which releases only NO), inhibited microglial
      prostanoid production, by preventing COX-2 expression. In contrast, in RAW 264.7
      cells, SIN-1 enhanced both basal and LPS-stimulated prostanoid production by
      upregulating COX-2, while SNAP stimulated basal production and slightly inhibited
      the LPS-induced production, as a cumulative result of enhanced AA release and
      depressed COX-2 expression. Thus, reactive nitrogen intermediates can influence
      prostanoid production at distinct levels and in different way in the two cell
      types, and results obtained with RAW 264.7 cells can not be extrapolated to
      microglia.

PMID- 9280305
TI  - Clathrin interacts specifically with amphiphysin and is displaced by dynamin.
AB  - Amphiphysin is an SH3 domain protein that has been implicated in synaptic vesicle
      endocytosis. We have recently cloned a second amphiphysin isoform, Amph2
      (sequence submitted to GenBank, Y13380). Proteins capable of forming a complex
      with amphiphysin were isolated from rat brain by using recombinant GST-Amph2 for
      binding experiments. As well as interacting with dynamin I, the full-length
      protein bound to a weaker 180-kDa band. Immunoblotting demonstrated this protein
      to be clathrin. To address whether this is a direct interaction, the clathrin
      binding to amphiphysin was reconstituted in vitro with purified proteins. The N
      terminal domain of Amph2 is sufficient for clathrin binding. Dynamin, which
      interacts with the SH3 domain of Amph2, displaces clathrin from the N-terminus.
      We propose a model that may explain how clathrin and dynamin are recruited to non
      overlapping sites of the coated pit.

PMID- 9280306
TI  - Role of protein kinase C and carboxyl-terminal region in acute desensitization of
      vasopressin V1a receptor.
AB  - The role of protein kinase C activation and carboxyl-terminal region in rapid
      desensitization of the vasopressin V1a receptor was investigated in Xenopus
      oocytes. Preincubation of the oocytes with vasopressin or with the diacylglycerol
      analog 1-oleoyl-2-acetyl-sn-glycerol (OAG), or direct injection of active protein
      kinase C, all blunted the calcium response of the V1a receptor. Truncation of the
      51 terminal amino acids (S374STOP) modified neither the intracellular calcium
      response to vasopressin nor its desensitization by vasopressin or OAG. These data
      suggest that desensitization of the V1a receptor is mediated by PKC activation
      and that its carboxyl-terminal domain is not required for signal transduction and
      rapid desensitization.

PMID- 9280307
TI  - Functional analysis of a rat sodium channel carrying a mutation for insect knock
      down resistance (kdr) to pyrethroids.
AB  - Pyrethroid insensitivity in resistant (kdr) insects has been correlated with a
      leucine to phenylalanine replacement in the S6 transmembrane segment of domain II
      of the axonal sodium channel alpha(para)-subunit. An alpha-subunit of rat brain
      type II sodium channel containing this mutation has been expressed and its
      sensitivity to permethrin compared with that of the wild-type channel. The steady
      state activation curve of the mutant was shifted 14 mV in the depolarizing
      direction. We propose that an equivalent shift of the sodium current activation
      curve in kdr insects could account for their low sensitivity to permethrin
      toxicity.

PMID- 9280308
TI  - The cytochrome oxidase subunit 1 gene (cox1) from the dinoflagellate,
      Crypthecodinium cohnii.
AB  - To date, no genes have been characterized from dinoflagellate mitochondrial DNA.
      Here we present the complete sequence of the gene (cox1) encoding subunit 1 of
      cytochrome c oxidase in the dinoflagellate, Crypthecodinium cohnii. Analysis of
      nucleotide and deduced amino acid sequences predicts a protein of 523 amino acids
      that is translated using universal initiation, stop and tryptophan codons. COX1
      amino acid identity and phylogenetic tree analyses strongly support a close
      evolutionary relationship between dinoflagellates and apicomplexans; however,
      inclusion of the ciliates in this clade is less well supported, a result likely
      due to the highly derived nature of ciliate COX1 sequences.

PMID- 9280309
TI  - The catalytic domain of dihydrolipoyl acetyltransferase from the pyruvate
      dehydrogenase multienzyme complex of Bacillus stearothermophilus. Expression,
      purification and reversible denaturation.
AB  - A sub-gene encoding the catalytic (acetyltransferase) domain (E2pCD) comprising
      residues 173-427 of the dihydrolipoyl acetyltransferase (E2p) chain of the
      pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus was
      expressed in Escherichia coli. The product assembled to form the characteristic
      icosahedral (60-mer) core structure with full catalytic activity. The Km values
      for dihydrolipoamide and acetyl-CoA were 1.2 mM and 13 microM, respectively.
      Dissociation of the icosahedral E2pCD into monomers by exposure to guanidine
      hydrochloride and the subsequent reassociation by gradual removal of the
      denaturing agent demonstrated the ability of the polypeptide chain to fold and
      reassemble in the absence of chaperonins.

PMID- 9280310
TI  - Modulation by (iso)flavonoids of the ATPase activity of the multidrug resistance
      protein.
AB  - The multidrug resistance protein (MRP) is an ATP-dependent transport protein for
      organic anions, as well as neutral or positively charged anticancer agents. In
      this study we report that dinitrophenyl-S-glutathione increases ATPase activity
      in plasma membrane vesicles prepared from the MRP-overexpressing cell line
      GLC4/ADR. This ATPase stimulation parallels the uptake of DNP-SG in these
      vesicles. We also show that the (iso)flavonoids genistein, kaempferol and
      flavopiridol stimulate the ATPase activity of GLC4/ADR membranes, whereas
      genistin has no effect. The present data are consistent with the hypothesis that
      certain (iso)flavonoids affect MRP-mediated transport of anticancer drugs by a
      direct interaction with MRP.

PMID- 9280311
TI  - Cloning and characterization of subtracted cDNAs from a human ciliary body
      library encoding TIGR, a protein involved in juvenile open angle glaucoma with
      homology to myosin and olfactomedin.
AB  - A group of cDNAs isolated from a subtractive ciliary body library of a normal
      human eye donor revealed 100% identity with TIGR a candidate gene responsible for
      juvenile open zangle glaucoma [Science 275 (1997) 668-670]. Several structural
      features of the deduced human protein have been noted: a cleavable N-terminal
      signal peptide, a periodic repetition at the N-terminus of leucine and arginine
      residues at every seventh and eleven position respectively in helix conformation
      (leucine zipper-like motif) exhibiting homology with myosin, and with
      olfactomedin in the C-terminus. The mRNA for TIGR is abundantly expressed in the
      ciliary body, iris, heart and skeletal muscle.

PMID- 9280312
TI  - Cyclosporine A is an uncompetitive inhibitor of proteasome activity and prevents
      NF-kappaB activation.
AB  - Cyclosporine A is an immunosuppressive agent that is used clinically in the
      prevention of transplant rejection and development of graft-versus-host disease.
      Recently, cyclosporine A has been shown to possess anti-inflammatory properties
      and is capable of inhibiting lipopolysaccharide-induced NF-kappaB activation.
      Ubiquitin-mediated proteasomal proteolysis plays a critical role in signal
      induced NF-kappaB activation since it regulates both IkappaB degradation and p105
      processing, it is also involved in the production of peptides for the assembly of
      MHC class I molecules. We report here that cylcosporine A acts as an
      uncompetitive inhibitor of the chymotrypsin-like activity of the 20S proteasome
      in vitro and that it suppresses lipopolysaccharide-induced IkappaB degradation
      and p105 processing in vivo demonstrating that inhibition of proteasome
      proteolysis is the mechanism by which cyclosporine A prevents NF-kappaB
      activation. A structurally unrelated immunosuppressant, rapamycin, did not
      inhibit the 20S proteasome in vitro.

PMID- 9280313
TI  - Characterization of the interaction between the light chain of factor VIIa and
      tissue factor.
AB  - Factor VIIa (fVIIa) consists of a heavy chain (serine protease domain) and a
      light chain (gamma-carboxyglutamic acid (Gla)-rich and epidermal growth factor
      (EGF)-like domains). The light chain, primarily the first EGF-like domain,
      appears to provide most of the binding energy in the interaction with tissue
      factor (TF). The Ca2+-binding sites in the protease domain and in the first EGF
      like domain influence activity and interaction with TF, but the contribution from
      the Ca2+-binding sites in the Gla domain has not been established. We have
      compared the soluble TF (sTF)-binding properties of intact fVIIa to those of a
      fragment comprising almost the entire light chain and a small disulphide-linked
      peptide from the protease domain. Half-maximal binding of fVIIa and the light
      chain to sTF occurred around 0.3 and 1 mM Ca2+, respectively. The Ca2+ dependence
      of light-chain binding indicates an influence of Ca2+ binding to the Gla domain
      on the interaction between fVIIa and sTF. Comparison of the sTF-binding
      properties of fVIIa and a truncated variant lacking the Gla domain suggests that
      this domain interferes with sTF association at suboptimal Ca2+ concentrations.
      The light chain of fVIIa associated 5-fold slower with sTF than did fVIIa at
      saturating Ca2+ concentrations, whereas the dissociation of its complex with sTF
      was at least 100-fold faster than that of fVIIa:sTF. This gave a dissociation
      constant of 1-2 microM for the interaction between the light chain and sTF
      compared to about 3 nM for the fVIIa:sTF interaction.

PMID- 9280314
TI  - Identification of potential ferric binding residues in the iron-binding protein
      of pathogenic Neisseria meningitidis through structure-based multiple sequence
      alignments.
AB  - The ferric iron-binding proteins of pathogenic Neisseria display structural and
      metal-binding properties characteristic of the transferrin family. In the absence
      of structural data for the ferric iron-binding proteins, spacial folding
      templates have been derived for the meningococcal protein from complete and
      partial structure-based multiple sequence alignments with structurally related
      proteins. The templates have been used to identify a number of potential iron
      binding residues. These include four residues that are identical with the iron
      coordinating ligands of transferrin, but only two reside within equivalent
      structural elements.

PMID- 9280315
TI  - The mouse filensin gene: structure and evolutionary relation to other
      intermediate filament genes.
AB  - Filensin and phakinin are two lens-specific members of the intermediate filament
      (IF) superfamily of proteins. They coassemble to form a beaded submembraneous
      filamentous network, the beaded filaments (BFs). The low sequence homology and
      differences in assembly compared to other IF proteins do not allow their
      classification in any of the five IF subgroups. The organization of the phakinin
      gene exon/intron boundaries provides evidence that this partner may be sharing a
      common origin with type I cytokeratin genes. Here we report the molecular
      cloning, sequence and characterization of the mouse filensin gene. The filensin
      gene consists of 8 exons and 7 introns, with 6 introns interrupting its rod
      domain in a highly conserved manner characteristic of type III IF genes, like
      vimentin, desmin, or peripherin. Of the two tail domain exons the one adjacent to
      the rod domain, compares to exon 7 of the non-neuronal cytoplasmic IF gene of
      helix aspersa and to the lamin region bridging the end of the rod domain to the
      nuclear localization signal. Altogether, these observations indicate that the
      lens beaded filaments form an independent class of IF.

PMID- 9280316
TI  - Design of sensitive fluorogenic substrates for human cathepsin D.
AB  - Cathepsin D is a lysosomal aspartic proteinase that has been implicated in
      several pathological processes such as breast cancer and Alzheimer's disease. We
      designed and synthesized a number of quenched fluorogenic substrates with P2
      variations in the series AcEE(EDANS)KPIXFFRLGK(DABCYL)E-NH2, where X=cysteine,
      methylcysteine, ethylcysteine, tert-butylcysteine, carboxymethylcysteine,
      methionine, valine or isoleucine. Most of the fluorogenic substrates exhibited
      greater k(cat)/Km ratios than the best cathepsin D substrates described so far.
      Differences in kinetic constants, which were rationalized using structure-based
      modeling, might make certain substrates useful for particular applications, such
      as active site titrations or initial velocity determination using a fluorescent
      plate reader.

PMID- 9280317
TI  - The soluble hyaluronidase from bull testes is a fragment of the membrane-bound PH
      20 enzyme.
AB  - The membrane-bound PH-20 hyaluronidase is known to be essential for
      fertilization. Here we addressed the question whether the soluble hyaluronidase
      from bull teste is related to the PH-20 polypeptide. The sequence of the membrane
      bound PH-20 hyaluronidase from bovine sperm was determined via cDNA cloning. In
      parallel, from a commercial preparation of bovine hyaluronidase the major 60-kDa
      form was purified to apparent homogeneity. The soluble enzyme was digested with
      two different proteases and with cyanogen bromide and the amino acid sequence of
      44 different fragments was determined. All the peptide sequences could be aligned
      to the sequence deduced from the cloned cDNAs. Our results thus show that the
      soluble 60-kDa hyaluronidase from bovine testes is a glycoprotein derived from
      the sperm PH-20 enzyme. As compared to the primary translation product of the PH
      20 mRNA, it lacks the signal peptide at the amino terminus and 56 amino acids at
      the carboxyl end. These results demonstrate that the soluble 60-kDa enzyme is a
      fragment of the PH-20 hyaluronidase. It is currently not known whether the
      soluble testes hyaluronidase has a distinct biological function.

PMID- 9280319
TI  - Validity of statistical techniques in assessing conclusions drawn from serologic
      tests.

PMID- 9280318
TI  - The biochemical consequences of alpha2,6(N) sialyltransferase induction by
      dexamethasone on sialoglycoprotein expression in the rat H411e hepatoma cell
      line.
AB  - Previous studies have demonstrated sialyltransferase (ST) enzyme activity to be
      induced in hepatic cells by corticosteroids. In this study, we used the H411e rat
      hepatoma cell line to further characterise this induction with particular
      reference to the subsequent changes in the pattern of sialoglycoprotein (SGP)
      expression. The induction of total ST activity by dexamethasone was concentration
      dependent with maximum induction occurring 12 h subsequent to drug addition.
      Western blot analysis demonstrated that the induction was associated with an
      increase in the expression of the alpha2,6(N) ST enzyme with no change in the
      expression levels of the alpha2,3(N) enzyme. While the induction resulted in an
      increase in the reaction velocity (Vmax) of the enzyme for both the sugar donor
      (CMP-Neu5Ac) and the asialofetuin acceptor protein, there was no significant
      change in the enzyme affinity (Km) for the substrates, suggestive of either an
      increase in the expression or efficiency of the existing enzyme(s) rather than an
      induction of novel ST enzymes. Lectin blot analysis of cellular glycoprotein
      expression demonstrated no change in the expression patterns of either alpha2,3
      or alpha2,6-linked SGP following enzyme induction. These results suggest that the
      available acceptor sites for the terminal sialic acid group(s) may be fully
      occupied in the control cells and therefore there are no further sites onto which
      the sialic acid can be transferred following induction of ST enzyme activity.
      This may be due to the high basal enzyme levels in the control cells already
      exhausting endogenous acceptor sites.

PMID- 9280320
TI  - Quantification of CD34+ cells: comparison of methods.
AB  - BACKGROUND: Quantification of CD34+ stem and progenitor cells is predominantly
      performed by flow cytometric analysis of cells prepared by whole blood staining
      and red cell lysis. This method also includes cell washing, which is thought to
      cause the destruction and loss of some of the nucleated cells (NCs). To address
      this cell loss and its influence on the outcome of enumeration, three techniques
      for preparing cells for quantification of CD34+ cells were compared. STUDY DESIGN
      AND METHODS: Blood (n = 179), bone marrow (n = 60), and leukapheresis components
      (n = 64) were examined by the use of density separation of mononuclear cells
      (MNCs) and two red cell-lysis procedures (wash and no-wash). Cell counts were
      determined in the original materials and after cell preparation. Absolute CD34+
      cell counts were calculated using the flow cytometry-analyzed proportions of
      CD34+ cells and the various white cell counts. RESULTS: Depending on the cell
      source and the cell preparation chosen, the loss of NCs ranged between 12 percent
      and 89 percent of the original white cell number. This loss of NCs was
      exclusively due to cell washing and predominantly affected granulocytic cells.
      Analysis of the flow cytometry data revealed that the relative CD34+ values in
      blood and bone marrow were roughly threefold higher in density separated MNCs
      than in those that underwent the lyse-and-wash procedure. Calculation of absolute
      CD34+ cell counts confirmed that the MNC procedure underestimated the CD34+ cell
      content by a median of 26 percent (blood), 21 percent (bone marrow), and 5
      percent (leukapheresis component) when compared with the median yield from
      analysis and cell counting performed after the lyse-and-wash procedure. On the
      other hand, the conventional lysis procedure, which applies the original white
      cell counts for CD34+ quantification, was shown to overestimate the CD34+ cell
      content by a median of 1.2-fold, 1.33-fold, and 1.13-fold, respectively.
      CONCLUSION: Neither density separation nor the whole-blood lysis procedure seems
      appropriate for optimal CD34+ quantification.

PMID- 9280321
TI  - Hemostasis in patients with severe von Willebrand disease improves after normal
      platelet transfusion and normalizes with further correction of the plasma defect.
AB  - BACKGROUND: A defective hemostatic effect of plasma concentrate infusion in
      patients with severe von Willebrand disease (vWD) has been ascribed to the
      absence of platelet von Willebrand factor (vWF) STUDY DESIGN AND METHODS: The
      role of platelet vWF in hemostasis of severe vWD was investigated. A
      plateletpheresis unit (4-5 x 10(11) platelets) from a normal compatible donor was
      transfused before any cryoprecipitate infusion to three type 3 vWD patients and
      to one patient with severe type 1 vWD with low levels of platelet vWF who
      required replacement therapy for bleeding episodes. Autologous platelets were
      transfused to one of the patients with type 3 vWD. RESULTS: Partial corrections
      of bleeding times (14-17 min vs. baseline >30 min) were observed in all patients
      after the transfusion of normal platelets. During cryoprecipitate infusion,
      bleeding times were normalized (<6 min), and bleeding episodes stopped when
      plasma levels of vWF activity ranged from 14 to 18 U per dL. Platelet
      interactions with the subendothelium increased in parallel with the correction of
      bleeding times. These results indicate that if approximately 20 percent of the
      total number of platelets have normal vWF antigen and if plasma vWF levels are at
      least 14 U per dL, then bleeding times will normalize and mucosal hemorrhages
      will stop. Transfusion of autologous platelets in one patient with type 3 vWD did
      not modify bleeding times or platelet adhesion on the subendothelium. CONCLUSION:
      The hemostatic effect of normal platelets in type 3 vWD seems to be related to
      the platelet vWF in the transfused platelets.

PMID- 9280322
TI  - Automated blood component collection with the MCS 3p cell separator: evaluation
      of three protocols for buffy coat-poor and white cell-reduced packed red cells
      and plasma.
AB  - BACKGROUND: Automated collection of blood components with a cell separator (MCS
      3p, Haemonetics), was performed according to three protocols. STUDY DESIGN AND
      METHODS: The first protocol provided 2 units of fresh-frozen plasma (FFP); and
      one buffy coat-poor red cell (RBC) concentrate in additive solution. The second
      protocol included an additional in-line filtration of the RBC in a closed system
      after storage at 4 degrees C for 24 hours. In the third protocol, an additional
      platelet concentrate (PC) was recovered from the buffy coat. Cell counts and
      biochemical characterization of the RBCs (n = 20 each) were determined on Days 0,
      1, 14, 28, and 49. RESULTS: The RBC volume was 336 +/- 9 mL (first protocol), 337
      +/- 7 mL (second protocol) and 293 +/- 12 mL (third protocol) with a hematocrit
      of 59 +/- 2, 53 +/- 3, and 61 +/- 5, percent respectively. On Day 49, hemolysis
      was 0.24 +/- 0.1 percent (first protocol), 0.33 +/- 0.32 percent (second
      protocol), and 0.38 +/- 0.1 percent (third protocol). The filtered RBC
      concentrate met the international standards for white cell-reduced RBCs.
      Filtration resulted in a clinically irrelevant increase of hemolysis. The in
      vitro RBC values (lactate dehydrogenase, 2-hydroxybutyrate dehydrogenase,
      hemolysis, potassium, 2,3 DPG, ATP) were at least equal to those in RBCs
      collected by conventional whole-blood donation. There is a trend toward extended
      preservation of 2,3 DPG in RBCs collected by apheresis. Two units of FFP could be
      collected with each donation (first protocol: 420 +/- 55 mL, 5.4 +/- 7
      WBCs/microL, 6.5 +/- 5 x 10(3) platelets/microL; second protocol: 440 +/- 33 mL,
      3 +/- 5.2 WBCs/microL, 32 +/- 12 x 10(3) platelets/microL; third protocol: 398 +/
      32 mL, 5 +/- 12 WBCs/microL; 3.4 +/- 3.5 x 10(3) platelets/microL). PCs prepared
      from the buffy coat collected by the third protocol contained 90 +/- 30 x 10(9)
      platelets in 88 +/- 14 mL of plasma. In vitro test results in these PCs were
      superior to those in PCs collected by conventional whole-blood donation. The
      procedure was well tolerated by all donors. No adverse reactions appeared.
      CONCLUSION: Erythroplasmapheresis with the MCS 3p cell separator is a useful
      alternative to conventional whole-blood donation and separation.

PMID- 9280323
TI  - Anaphylatoxins in fresh-frozen plasma.
AB  - BACKGROUND: Fresh-frozen plasma (FFP) is widely used in patients with coagulation
      disorders and simultaneous complement activation. Complement activation in FFP
      itself is poorly investigated. STUDY DESIGN AND METHODS: The concentration of
      anaphylatoxins C3a and C5a, the complement precursors C1q and factor B, and
      complement function were measured in 40 consecutively administered FFP units in
      two pediatric neonatal intensive care units. In 12 samples, the measurements were
      also performed after incubation with inulin. RESULTS: In 15 of 40 FFP units, both
      anaphylatoxin concentrations were below the upper cutoff levels reported for
      healthy humans (C3a, 500 microg/L; C5a, 5 microg/L). Anaphylatoxin levels were
      higher in FFP units produced by apheresis than in those from blood donation.
      Complement activation of FFP by inulin increased anaphylatoxin concentration,
      whereas C1q and factor B levels, and complement function remained unchanged.
      CONCLUSION: Elevated concentrations of anaphylatoxin are frequently found in FFP
      units produced by apheresis. Studies are necessary to investigate the reasons for
      complement activation and the possibilities of prevention during apheresis. As
      the concentrations of complement precursors and complement function did not
      change with activation in FFP, these studies should include measurement of the
      anaphylatoxins C3a and C5a.

PMID- 9280324
TI  - Effects of gamma irradiation on red cells from donors with sickle cell trait.
AB  - BACKGROUND: Transfusion-associated graft-versus-host disease can be prevented by
      gamma irradiation of blood components. Red cells (RBCs) from sickle cell disease
      patients may exhibit oxidative changes of RBC membranes due to the instability of
      hemoglobin (Hb) S. Persons with sickle cell trait are eligible to donate blood,
      and 35 to 45 percent of their total Hb is Hb S. The effect of gamma irradiation
      on RBCs from such persons is of interest. STUDY DESIGN AND METHODS: RBCs from 12
      donors with sickle cell trait (Hb AS) and from 12 with normal Hb (Hb AA) were
      studied. Each of the 24 RBC units was divided equally into two transfer bags via
      a sterile connecting device. One bag from each RBC unit received a 2500-cGy dose
      of gamma irradiation at its mid-plane and was stored at 4 degrees C; the second
      set of bags was stored without irradiation. For RBCs from 6 donors with Hb AS and
      6 donors with Hb AA, units were irradiated on Day 7 and studied on Day 35 of
      storage (Group 1). For the RBCs from the other 6 donors with Hb AS and the other
      6 donors with Hb AA, units were irradiated on Day 28 and studied on Day 42 of
      storage (Group 2). RESULTS: For Group 1 and Group 2, plasma potassium and plasma
      Hb concentrations were significantly higher and RBC ATP concentrations were
      slightly lower in the irradiated units than in the nonirradiated units. In Group
      1 and Group 2, there were no significant differences in the plasma potassium or
      RBC ATP concentrations in either the irradiated or the nonirradiated units of
      RBCs from donors with Hb AS and donors with Hb AA. Plasma Hb concentrations were
      consistently lower in the units from donors with Hb AS, whether or not they were
      irradiated. However, in both groups, proportionally similar changes in plasma Hb
      concentration were detected when the irradiated Hb AS and Hb AA units were
      compared to nonirradiated Hb AS and Hb AA units. CONCLUSION: Gamma irradiation of
      RBCs from donors with Hb AS or with Hb AA resulted in comparable changes in
      plasma potassium, RBC ATP, and plasma Hb concentrations, although donors with Hb
      AS had lower plasma Hb. RBCs from donors with Hb AS subjected to 2500 cGy of
      gamma irradiation did not evidence a storage lesion greater than that seen in
      RBCs from donors with Hb AA.

PMID- 9280325
TI  - Flow cytometric analysis of platelet membrane antigens during and after
      continuous-flow plateletpheresis.
AB  - BACKGROUND: The influence, extent, and duration of changes in platelet antigen
      expression caused by blood-biomaterial interaction in plateletpheresis were
      assessed. STUDY DESIGN AND METHODS: Twenty-two apheresis donors were studied by
      using two automated continuous-flow apheresis devices. Blood samples were taken
      before, during, and for 4 days after extracorporeal circulation. The platelet
      surface expression of glycoproteins CD41a, CD42b, CD62p, and CD63 was analyzed by
      flow cytometry. RESULTS: Over the course of plateletpheresis, there was a
      significant increase in mean channel fluorescence intensity (MCFI) of CD62p, from
      25.1 +/- 7.9 (mean +/- SD) to 50.4 +/- 28.9, and of CD63, from 22.3 +/- 6.5 to
      33.3 +/- 13.2. There was a significant decrease in CD41a expression as measured
      by the MCFI, from 1129.8 +/- 125.0 to 1066.6 +/- 102.2, and in CD42b MCFI, from
      329.6 +/- 49.4 to 321.4 +/- 52.0. The two apheresis devices showed different
      platelet activation kinetics, but the overall MCFI of CD62p and CD63 did not
      significantly diverge after 60 minutes of apheresis. CD62p and CD63 expression as
      measured by the MCFI returned to preapheresis levels during the follow-up period
      in 25 and 25 of 44 procedures, respectively, within 24 hours; in 10 and 13 of 44
      procedures after 48 hours; in 7 and 3 of 44 procedures after 72 hours; and in 2
      and 3 of 44 procedures on Day 5. CONCLUSION: The varying kinetics of expression,
      as measured by the MCFI, of platelet antigens CD62p, CD63, CD41a, and CD42b
      during extracorporeal circulation may be useful for biocompatibility testing.
      Activated platelets continue to circulate in donors for several days after
      cytapheresis, which suggests that a sufficient interval between apheresis
      procedures is necessary to avoid the collection of activated platelets.

PMID- 9280326
TI  - Misinterpretation and misapplication of p values in antibody identification: the
      lack of value of a p value.

PMID- 9280328
TI  - A pilot study of continuous ambulatory electrocardiography in patients donating
      blood for autologous use in elective coronary artery bypass grafting.
AB  - BACKGROUND: A pilot study was conducted to evaluate the impact of a single
      autologous blood donation on the presence or absence of myocardial ischemic
      episodes in patients with coronary artery disease. STUDY DESIGN AND METHODS:
      Fifty patients scheduled for elective coronary artery bypass grafting underwent
      two 24-hour periods of ambulatory electrocardiogram monitoring, one before and
      one after their first autologous blood donation. The presence or absence and the
      number, duration, and integral area of episodes of ST segment depression for each
      24-hour monitoring period were determined. RESULTS: Forty-two patients had
      legible electrocardiogram recordings for both monitoring periods. Of these, 36
      patients (86%) had at least one episode of ST segment depression during any
      monitoring period. The number of patients who had at least one episode of ST
      segment depression before donation was not significantly different from the
      number of those who had at least one episode after donation (31 and 33 patients,
      respectively; p = 0.73). CONCLUSION: Donating a unit of blood had no demonstrable
      effect on the presence or absence of myocardial ischemic episodes in this sample
      of 42 autologous blood donors with coronary artery disease. The results of this
      study should be validated in further trials.

PMID- 9280327
TI  - Maternal immunization to Gov system alloantigens on human platelets.
AB  - BACKGROUND: Immunization to platelet alloantigens can occur during pregnancy or
      after the transfusion of blood components. Platelet alloantibodies can cause
      neonatal alloimmune thrombocytopenia and posttransfusion purpura. Transfusion
      induced alloimmunization to a novel platelet alloantigen system, Gov, expressed
      on the 175-kDa glycosyl phosphatidylinositol-anchored platelet glycoprotein,
      CD109, was previously described. This report describes three unrelated patients
      who were alloimmunized to Gov(a) or Gov(b) during pregnancy. STUDY DESIGN AND
      METHODS: Platelets were typed by using radioimmunoprecipitation for HPA-1a, -3a, 
      5a, -5b, Gov(a), and Gov(b) and by polymerase chain reaction-restriction fragment
      length polymorphism for HPA-1a, -1b, -3a, and -3b. Maternal sera were screened
      for platelet antibodies by using radioimmunoprecipitation and the antigen capture
      assay. RESULTS: Patients 1 and 2 were investigated after the diagnosis of
      neonatal alloimmune thrombocytopenia in their children, and alloantibodies
      specific for Gov(b) and Gov(a), respectively, were detected in maternal serum.
      Serum from patient 3, who had mild idiopathic thrombocytopenia purpura with no
      detectable autoantibody, was found to contain alloantibodies to Gov(b) and to HPA
      5b, presumably as a result of immunization during pregnancy. Platelet typings
      confirmed that the patients were at risk for alloimmunization to the respective
      antigen. CONCLUSION: This report of three cases of maternal alloimmunization to
      antigens in the Gov system indicates that immunization can occur via placental
      transfer of antigen and that Gov system alloantibodies may be associated with
      neonatal alloimmune thrombocytopenia.

PMID- 9280329
TI  - Serologic test for syphilis as a surrogate marker for human immunodeficiency
      virus infection among United States blood donors.
AB  - BACKGROUND: This study evaluated the usefulness of the serologic test for
      syphilis (STS) in preventing the transmission of human immunodeficiency virus
      (HIV), hepatitis B and C viruses, and human T-lymphotropic virus via the
      transfusion of seronegative, infectious window-period blood. STUDY DESIGN AND
      METHODS: Demographic and laboratory information on blood donations made between
      January 1992 and June 1994 in 18 American Red Cross regions was analyzed. It was
      assumed that the same proportion of HIV-positive and HIV-infectious window-period
      donations reacted on STS and were negative on other screening tests (hepatitis B
      and C viruses and human T-lymphotropic virus). This proportion multiplied by the
      estimated number of HIV-infectious window-period donations is the number of post
      screening HIV-infectious donations removed by STS. RESULTS: Of 4,468,570
      donations, 12,145 (0.27%) were STS positive and 377 (0.008%) were HIV positive.
      Among donations that were negative on other screening tests, STS-reactive
      donations were 12 times more likely to be HIV positive (odds ratio = 11.9; 95% CI
      = 5,26). However, of an estimated 13 infectious window-period donations, 0.2
      would have been removed because of a reactive STS, at a cost of over $16 million.
      CONCLUSION: STS is a poor marker and a costly strategy for preventing post
      screening HIV infections and other blood-borne diseases.

PMID- 9280330
TI  - Human immunodeficiency virus (HIV) antibodies detected by new assays that are
      enhanced for HIV-1 subtype O.
AB  - BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) subtype O infections are
      not reliably detected by commonly used anti-HIV-1/2 screening assays. Therefore,
      anti-HIV-1/2 assays have been modified to increase their sensitivity in detecting
      antibodies to HIV-1 subtype O. STUDY DESIGN AND METHODS: Two new anti-HIV-1/2
      enzyme-linked immunosorbent assays (ELISAs) (Abbott Plus and Ortho Enhanced) were
      compared with a currently used anti-HIV-1/2 ELISA (Abbott Recombinant) in various
      serum panels: 91 Western blot-confirmed anti-HIV-1-positive samples, 20 samples
      from Western blot-confirmed HIV-1-infected patients in log3 serial dilutions, and
      1463 samples from consecutive, volunteer, nonremunerated blood donors. RESULTS:
      Among 91 anti-HIV-1 Western blot-positive samples, 2 (2.2%) were missed by the
      Abbott Recombinant ELISA, but all 91 were detected by the Abbott Plus and Ortho
      Enhanced ELISAs. In contrast, two discrepant samples were found to react in viral
      lysate-based assays. In serial dilutions, Ortho Enhanced ELISA was significantly
      less sensitive than the Abbott Recombinant and Abbott Plus ELISAs, with the
      latter two being of comparable sensitivity. The specificities of Abbott
      Recombinant, Abbott Plus, and Ortho Enhanced ELISAs in 1463 blood donors were
      100, 99.93, and 99.86 percent, respectively. Routine testing of 29,102 donations
      with the enhanced Abbott Plus ELISA revealed a specificity of 99.93 percent.
      CONCLUSION: Two Western blot-confirmed anti-HIV-1-positive samples were missed by
      the Abbott Recombinant ELISA but detected by the Abbott Plus and Ortho Enhanced
      ELISAs. The analytic sensitivity of the Ortho Enhanced ELISA was inferior to that
      of both Abbott ELISAs. The specificities of the Abbott Recombinant, Abbott Plus,
      and Ortho Enhanced ELISAs were comparable.

PMID- 9280331
TI  - Performance of three generations of anti-hepatitis C virus enzyme-linked
      immunosorbent assays in donors and patients.
AB  - BACKGROUND: Prevention of posttransfusion non-A,non-B hepatitis in recipients of
      blood components improved considerably with the introduction of the second
      generation of hepatitis C virus (HCV) antibody tests. In 1993, third-generation
      HCV antibody assays were introduced in Europe. STUDY DESIGN AND METHODS: The
      performance of three generations of anti-HCV enzyme-linked immunosorbent assay
      (ELISA) (ELISA-1, -2, -3) was compared in routine blood donor screening (99,394
      donations were tested with ELISA-1, 167,999 donations with ELISA-2, and 262,090
      donations with ELISA-3) and in serial samples from nine patients with documented
      acute posttransfusion HCV infection. RESULTS: Eight (0.01%) repeat donors,
      previously negative in ELISA-1, were found positive in ELISA-2 and were confirmed
      as positive in second-generation recombinant immunoblot assay and/or cDNA
      polymerase chain reaction. In the donor population, no difference in the
      sensitivity of ELISA-2 and -3 was observed. The specificity of the three
      generations of ELISAs was comparable (99.8, 99.7, and 99.7%). In seroconversion
      samples, ELISA-2 and -3 detected HCV antibodies at the same time in seven
      patients, but in two patients, ELISA-3 found HCV antibodies, respectively, 63 and
      77 days earlier than ELISA-2 did. In the seroconversion samples, ELISA-2 and -3
      were significantly more sensitive than second- and third-generation recombinant
      immunoblot assays. CONCLUSION: ELISA-3 did not detect more HCV-infected
      individuals in a donor population that previously tested negative in ELISA-2, but
      it did detect HCV antibodies earlier in some patients with acute HCV infection.
      ELISA-2 and -3 were significantly more sensitive than second- and third
      generation recombinant immunoblot assays.

PMID- 9280332
TI  - A highly sensitive and specific chemiluminescent enzyme-linked immunosorbent
      assay for diagnosis of active Trypanosoma cruzi infection.
AB  - BACKGROUND: Chagas' disease is transmitted to man either by the bite of insects
      harboring Trypanosoma cruzi or by the transfusion of blood from infected donors.
      The conventional serologic testing as presently used in blood banks in South
      America is unsatisfactory, because of a high number of inconclusive and false
      positive results. Other methods such as polymerase chain reaction and enzyme
      linked immunosorbent assay (ELISA) with recombinant antigens have been proposed,
      but inherent difficulties have so far precluded their adoption in the large-scale
      screening required by blood banks. STUDY DESIGN AND METHODS: A highly sensitive
      and specific chemiluminescent ELISA using a purified trypomastigote
      glycoconjugate antigen and a complex epimastigote antigen was devised for the
      diagnosis of active T. cruzi infection. RESULTS: Chemiluminescent ELISA was 100
      percent sensitive in the diagnosis of 100 cases of confirmed Chagas' disease.
      Inconclusive results and false-positive reactions were eliminated in a panel of
      115 sera. The specificity of the chemiluminescent ELISA was 100 percent with a
      purified trypomastigote glycoconjugate antigen and 99.7 percent with a complex
      epimastigote antigen when applied to 1000 normal human sera and 288 heterologous
      sera from patients with other infections, including leishmaniasis, and vaccinated
      individuals. CONCLUSION: The chemiluminescent ELISAs provide a test that is
      highly sensitive (purified trypomastigote glycoconjugate and complex epimastigote
      antigens) and specific (purified trypomastigote glycoconjugate antigen) for
      Chagas' disease diagnosis. It can be used in blood bank screening and to monitor
      the treatment of patients undergoing chemotherapy.

PMID- 9280333
TI  - Immunologic events during the incubation period of hepatitis C virus infection:
      the role of antibodies to E2 glycoprotein. Multicentre Hemodialysis Cohort Study
      on Viral Hepatitis.
AB  - BACKGROUND: The study of the sensitivity of screening assays is greatly
      facilitated by testing the sequential changes in seroconverting individuals. The
      aim of this study was to investigate the early immunologic response after
      hepatitis C virus (HCV) infection and to evaluate whether HCV envelope (E2)
      recombinant antigen would provide a significant increase in sensitivity for
      detection of anti-HCV. STUDY DESIGN AND METHODS: Twenty hemodialysis patients who
      were seroconverting to anti-HCV were included in this study. They were followed
      up for a mean period (+/- SD) of 10.5 +/- 3.3 months, in which 13 to 46 serum
      samples per case were collected. Each sample was tested for anti-HCV by second-
      and third-generation enzyme immunoassay (EIA-2 and EIA-3) and recombinant
      immunoblot assay (RIBA-3). E2 antibodies were tested by a prototype EIA in which
      E2 was expressed as a recombinant antigen in Chinese hamster ovary cells.
      RESULTS: Alanine aminotransferase elevation was observed in 18 of 20 cases.
      Reactivity against c100, c33c, c22, NS5, and E2 was detected in 15 (75%), 19
      (95%), 15 (75%), 2 (10%), and 17 (85%) patients, respectively; c33c was the most
      immunogenic antigen, followed in descending order by E2, c22, c100, and NS5. E2
      antibody reactivity resolved the two RIBA-3-indeterminate cases. However, there
      was no case in which E2 reactivity preceded all other HCV antigens. Anti-E2 was
      found to react in all patients of genotypes 1a, 1b, and 3a but in only 2 of 4
      patients of genotype 4a. CONCLUSION: In this group of seroconverting individuals,
      E2 antigen was shown to be highly immunoreactive and did resolve some RIBA-3
      indeterminate samples as being positive, on the basis of reactivity to multiple
      antigens, but it did not improve early detection of seroconversion.

PMID- 9280334
TI  - Transfusion: the first decade: volume 8.

PMID- 9280335
TI  - Frozen platelets and platelet substitutes in transfusion medicine.

PMID- 9280336
TI  - On the high probability that a perceived lack of value of obtaining a p value
      will be detrimental to patient care.

PMID- 9280337
TI  - Testing of immunoglobulin products for hepatitis C virus by polymerase chain
      reaction: importance of an internal control.

PMID- 9280338
TI  - Gamma radiation does not prevent transfusion-induced HLA alloimmunization.

PMID- 9280339
TI  - Temporary deferral of blood donors after administration of hepatitis B vaccine.

PMID- 9280340
TI  - Loss of D and C expression in chronic myelomonocytic leukemia.

PMID- 9280341
TI  - Activators and repressors: making use of chromatin to regulate transcription.
AB  - Metazoans and yeast use enzymes that modulate histone acetylation and nucleosomal
      integrity in order to regulate transcription. Repressor complexes deacetylate
      histones and stabilize nucleosomes. Activator complexes acetylate histones and
      disrupt nucleosomes. Variation in chromatin structure makes a major contribution
      to gene regulation. Here we discuss the enzymatic complexes and molecular
      machines that make use of chromatin to control transcription.

PMID- 9280342
TI  - The duplex DNA is very underwound in the three-stranded RecA protein-mediated
      synaptic complex.
AB  - BACKGROUND: The RecA protein is a central player in bacterial homologous
      recombination. It promotes two key events: the search for homology between two
      DNA molecules and the subsequent formation of the synaptic complex composed of
      RecA and three DNA strands (two from one duplex and one single strand). In spite
      of numerous studies, the architecture of the synaptic complex is still far from
      clear. RESULTS: We have exploited two approaches to study the structure of
      Escherichia coli RecA protein-mediated DNA synapsis: chemical modification with
      potassium permanganate and treatment of synaptic complexes of different lengths
      with topoisomerase I. The linking number difference values, obtained after
      separation of the individual sets of topoisomers in an agarose gel, were used to
      determine the number of bases per helical turn. We were able to show that the
      topology of the three-stranded complexes containing RecA is quite different from
      that expected for deproteinized D-loops. The original duplex in the synaptic
      complex is unwound, but not necessarily unpaired, to a structure topologically
      equivalent to DNA with approximately 27 bp per turn. Despite the fact that the
      patterns of reactivity towards potassium permanganate cannot be interpreted
      unambiguously, the results of chemical footprinting can be explained in terms of
      a synaptic complex as an extended and unwound three-stranded helical structure.
      CONCLUSIONS: This work provides the first quantitative topological parameters for
      the RecA protein-mediated three-stranded synaptic complex. Furthermore, the
      structure of synaptic complexes is different from that of a simple D-loop.

PMID- 9280343
TI  - Identification of an extended half-site motif required for the function of
      peroxisome proliferator-activated receptor alpha.
AB  - BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) belong to the
      nuclear hormone receptor superfamily and regulate many genes of the proteins
      involved in lipid metabolism, including peroxisomal acyl-CoA oxidase (AOX).
      Through heterodimerization with retinoid X receptors (RXRs), PPAR was believed to
      recognize the sequence elements consisting of two directly repeating 6-bp half
      sites spaced by one nucleotide (DR-1), located in the regulatory regions of these
      genes. RESULTS: Employing the peroxisome proliferator-responsive enhancer of the
      rat AOX gene, we analysed the minimal sequence requirements for enhancer activity
      and PPARalpha/RXRalpha binding. We found that the sequence just downstream of the
      DR-1 motif is indispensable for both functions. By a direct selection procedure
      of high-affinity binding sites from a random sequence pool, we identified a
      consensus sequence at the four positions next to DR-1. We also suggest that
      PPARalpha binds to the downstream half-site, whereas RXRalpha binds to the
      upstream half-site of the AOX DR-1. CONCLUSIONS: An extended half-site of 10-bp,
      but not a simple 6-bp half-site, is required for the PPARalpha binding, upon
      heterodimer formation with RXRalpha. The binding polarity of PPARalpha/RXRalpha
      seems to be opposite to that of other RXR-involving heterodimers.

PMID- 9280344
TI  - Xenopus cyclin A1 can associate with Cdc28 in budding yeast, causing cell-cycle
      arrest with an abnormal distribution of nuclear DNA.
AB  - BACKGROUND: Cyclins play a regulatory role in cell cycle progression, associated
      with cyclin-dependent kinases. We have investigated the structure-function
      relationships of cyclin A, mainly using Xenopus egg extracts in vitro. To further
      analyse the function and structure of cyclin A in vivo, we expressed Xenopus
      cyclin A1 in the budding yeast Saccharomyces cerevisiae. RESULTS: We herein show
      that vertebrate cyclin A1 can associate with endogenous Cdc28 to form histone H1
      kinase. The growth of the yeast was inhibited by the expression of indestructible
      cyclin A1, but not by a non-Cdk binding cyclin A1 mutant. The induction of cyclin
      A1 expression in yeast caused cell cycle arrest with an abnormal distribution of
      nuclear DNA to the daughter bud. Suppressors of the cyclin A1-mediated growth
      arrest were identified as new alleles of the cdc28 mutation that reduced the
      binding of cyclin A1 and possessed different affinities for the cyclin-Cdc28
      complexes. The temperature-sensitivity of the cdc28 mutation was thus
      preferentially suppressed by the endogenous cyclins CLN2 and CLB2. CONCLUSIONS:
      These results suggest that the Cdc28 protein kinase activity mediated by
      vertebrate cyclin A1 may be involved in the process of nuclear movement in the
      yeast, and thereby affect the dependence of the M phase on the completion of the
      S phase through a preferential binding affinity of the cyclin-Cdc28 complex.

PMID- 9280345
TI  - A complete NotI restriction map covering the entire long arm of human chromosome
      11.
AB  - BACKGROUND: Human chromosome 11 is one of the autosomes on which many disease
      genes have been mapped. Many different types of map, including a radiation hybrid
      map, a genetic map, and an STS-content YAC map, have been constructed for the
      chromosome. However, a physical map providing accurate physical distances has not
      yet been established. A chromosome-wide NotI restriction map was constructed to
      understand the overall feature of the genome organization and to facilitate the
      positional cloning of disease genes. RESULTS: A complete NotI restriction map of
      the entire long arm of human chromosome 11 was constructed using linking-clone
      mapping. This physical map covers 77.6Mb, from a pericentromeric NotI site to the
      terminus, and provides the most accurate ordering and distance estimation to
      date. We also mapped 138 sequence markers in the q13 region that have been poorly
      mapped previously. CONCLUSIONS: The restriction map of the entire long arm of
      human chromosome 11 is the longest restriction map of the human genome. This
      mapping has disclosed unique features regarding the organization of the
      chromosome, indicating that restriction sites of NotI, a CpG-recognition enzyme,
      are primarily distributed in R (or T) bands and that genetic distance is
      considerably longer in R (or T) bands than in G bands. The mapping, as well as
      the dense concentration of mapped markers within the q13 region, should help with
      positional cloning of the genes associated with various diseases.

PMID- 9280346
TI  - Comparison of food intake, rate of consumption, pecking activity and behaviour in
      layer and broiler breeder males.
AB  - 1. The food intake, rate of food consumption (g/min) and behavioural time budgets
      of individually caged broiler and layer (white egg) males were compared in the
      early morning (1.5 to 3.5 h after onset of photoperiod) and afternoon (5.5 to 7.5
      h after photostimulation) on 4 different days at 11 to 12 weeks of age.
      Correlations among rate of consumption, the proportions of time on different
      activities and previously estimated scores for fearfulness were calculated. 2.
      Food intake and rate of consumption were two-fold greater in broilers than in
      layers. The proportion of time spent feeding in the morning was lower in layers
      compared with broilers and was similar in the afternoon. Rate of consumption was
      higher in the morning than in the afternoon in both lines. 3. Overall, a similar
      proportion of time was spent feeding, standing and sitting in both lines. The
      birds were more likely to be sleeping (eyes closed) in the afternoon than in the
      morning. 4. The proportions of time spent on preening, pecking and stereotypic
      pacing were greater in layers than in broiler breeders. The proportion of time
      spent drinking tended to be higher in broiler breeders than layers. 5. Two
      measures of fearfulness, aversion to a looming human and a novel rod were
      respectively positively and negatively correlated to time drinking and
      stereotypic pacing. 6. The time spent in stereotypic pacing was negatively
      related to rate of consumption and time spent preening. 7. The results suggest
      that low food intake is associated with increased arousal, fear and frequent
      feeding and drinking. There was no evidence that beak related activity was
      related to fearfulness.

PMID- 9280347
TI  - Distribution of blastodermal cells transferred to chick embryos for chimera
      production using windowed eggs.
AB  - 1. To improve the production of chimeras, the distribution of donor blastodermal
      cells after transferring into recipient embryos was examined morphologically. 2.
      Donor blastodermal cells were distributed near the site of injection in the
      epiblast and in the subgerminal cavity and yolk. Some filled the hole made by the
      micropipette and were distributed outside the epiblast. Many were buried in yolk.
      In some cases, more donor blastodermal cells were located in the yolk than in the
      subgerminal cavity and some were located 800 microm below the under-surface of
      the epiblast. 3. It is recommended that injection should be as shallow as
      possible to increase the proportion of chimeras produced, and that some means is
      needed to prevent blastodermal cells from escaping from the hole produced by
      injection.

PMID- 9280348
TI  - Inheritance of wing feather development rate in guinea fowl (Numida meleagris).
AB  - 1. A study of primary wing feather development rate in guinea fowl revealed
      genetic control through a single pair of sex-linked alleles. The allele for slow
      feathering (K) was dominant over that for rapid feathering (k+). 2. Wing feather
      sexing showed 94% accuracy in 10-d-old keets. 3. Incidence of rapid feathering
      allele (k+) was higher in the population selected for high body weight compared
      to the unselected population.

PMID- 9280349
TI  - Comparison of selection based on phenotype, selection index and best linear
      unbiased prediction using data from a closed broiler line.
AB  - 1. Selection based on three methods of estimating breeding values, Best Linear
      Unbiased Prediction (BLUP), selection index (SI), and phenotype (SP) were
      compared for three traits, juvenile body weight (JW), percentage breast meat
      yield (BM) and hen-day rate of egg production (EP) using records provided by a
      commercial broiler breeding company. 2. Product moment correlations were
      calculated between breeding values estimated by each method and averaged across
      sexes. A mean correlation of 0.69 was obtained between selection on SP and BLUP
      for JW. Mean correlations of 0.88 and 0.68 and 0.87 were obtained between SI and
      BLUP for the traits JW, EP and BM, respectively. 3. A mean estimated genetic
      response of 77.7% was obtained with SP for JW relative to BLUP in the absence of
      restrictions on the selection of close relatives. Estimated genetic responses of
      90.7%, 66.9% and 88.4% were obtained by SI relative to BLUP for JW, EP and BM,
      respectively. 4. Applying restrictions on the selection of close relatives
      resulted in slight decreases in estimated responses but not in the respective
      ranking of the selection methods. 5. The results indicate that BLUP could provide
      commercial breeders with increased selection responses compared to index
      selection, in particular for traits of low heritability and where relatively few
      animals possess performance records.

PMID- 9280350
TI  - Effect of vitamin A on the oxidative stability of broiler meat during storage:
      lack of interactions with vitamin E.
AB  - 1. An experiment was carried out with male broiler chicks to evaluate the
      combined effect of two concentrations of vitamin A (1.032 and 10.32 mg retinyl
      acetate/kg diet) and two concentrations of vitamin E (0 and 150 mg alpha
      tocopheryl acetate/kg diet) on the oxidative stability of the drumstick meat of
      broiler chickens. The experimental diets were fed from 1 to 42 d of age. The
      oxidative stability, evaluated by thiobarbituric acid reactive substances (TBARS)
      values, was determined after 125 d of storage at -18 degrees C. 2. TBARS values
      were very low and not significantly affected by dietary vitamins A and E or their
      combinations. However, the TBARS values in the meat of birds fed on the vitamin E
      free diets, but not on the vitamin E-supplemented diets, were markedly increased
      after using an accelerated test of oxidation of the meat lipids by incubation.
      This resulted in a significant (P<0.001) difference from vitamin E
      supplementation. Vitamin A, alone or in combination with vitamin E, did not
      affect TBARS values found after incubation. 3. It is concluded that vitamin A at
      the concentrations used had no effect on the oxidative stability of the meat, in
      contrast to the protective effect of vitamin E, and that there is no interaction
      between the effect of these two vitamins on meat stability.

PMID- 9280351
TI  - Comparative studies on the histochemical properties of M. iliotibialis lateralis
      from Kumamoto Cochin crossbred roaster and broiler chickens.
AB  - 1. Histochemical properties of M. iliotibialis lateralis were compared between
      Kumamoto Cochin (a Japanese native breed) crossbred roasters (KC roasters, 112 d
      of age) and normal broilers (56 d of age). 2. Myofibres were divided into Types
      II-R, II-I and II-W showing high, moderate and low reduced nicotinamide adenine
      dinucleotide dehydrogenase (NADH-DH) activities, respectively. 3. Subsarcolemmal
      formazan granules indicating very strong NADH-DH activity in Type II-R fibres
      were observed only in KC roasters. In both sexes the percentage of Type II-R
      fibres present was greater in KC roasters than in broilers. 4. These results
      indicated marked differences in histochemical properties and meat quality between
      KC roasters and broilers.

PMID- 9280352
TI  - Utilisation of squilla meal (a novel animal protein source) by broilers.
AB  - 1. The nutritive value of squilla meal, which contained 339 g crude protein, 18.6
      g ether extract, 72.8 g calcium, 17.2 g phosphorus and 7.13 MJ of apparent
      metabolisable energy/kg, was examined in 5 experiments with broilers. 2. Squilla
      meal contained less lysine (3.45 vs 6.74 g/16g nitrogen) and methionine (1.02 vs
      1.86/16 g nitrogen) than fish meal, had a lower protein digestibility coefficient
      (0.66 vs 0.72) and a lower gross protein value (68% vs 74%). 3. By gradually
      replacing the fish meal with squilla meal in isocaloric, isonitrogenous broiler
      diets it was shown that there was a linear decrease in broiler weight gain;
      efficiencies of food utilisation were also lower at all squilla meal substitution
      rates. Inclusion of squilla meal in the diets increased intestinal lengths. 4.
      Addition of a proteolytic enzyme to the diets containing squilla meal restored
      broiler weight gain and efficiency of food utilisation to that of birds fed on
      the control diet. 5. Diets containing autoclaved squilla meal resulted in reduced
      weight gain although efficiency of food utilisation was not affected.

PMID- 9280353
TI  - Influence of caecectomy and dietary protein concentration on apparent excreta
      amino acid digestibility in adult cockerels.
AB  - 1. The influence of caecectomy and dietary crude protein content (50, 100, 150,
      200 and 250 g/kg diet) on the apparent excreta amino acid digestibilities in
      adult cockerels fed on semi-purified diets containing soyabean meal (SBM) or
      cottonseed meal (CSM) as the sole source of protein was investigated. 2.
      Caecectomy had no influence on the apparent digestibilities of most amino acids
      in SBM, the exceptions being histidine, arginine and lysine, but lowered the
      apparent digestibility of amino acids in CSM. 3. The protein content in assay
      diets has a strong influence on the apparent amino acid digestibility values for
      poultry. Apparent values are lower when the dietary protein content is low. 4.
      The use of a single endogenous amino acid output value, generated by regression
      analysis or protein-free diets, for true digestibility adjustments across a wide
      range of protein intakes is questioned. In particular, such an application will
      penalise estimates of apparent digestibility when the dietary protein content is
      high.

PMID- 9280354
TI  - Utilisation of U-14C-lysine by young turkeys.
AB  - 1. U-14C-lysine was administered by tube into the crop to turkey poults fed on
      assay diets (maize + sesame + maize gluten meal) containing varying
      concentrations of lysine, and partition of the label into body components, carbon
      dioxide, and excreta was measured. 2. Deposition of 14C label into breast and
      heart muscles responded positively to dietary lysine concentration. There was no
      apparent relationship between dietary lysine intake and deposition of label into
      carbon dioxide or excreta. 3. Efficiency of lysine retention, above maintenance,
      was estimated to be 0.523 +/- 0.034. 4. Turkeys exhibited variable metabolic
      efficiency in the use of lysine as indicated by loss of U-14C-lysine label to
      expired carbon dioxide and to excreta by individual turkeys.

PMID- 9280355
TI  - Effects of sex, age and food intake upon metabolisable energy values in broiler
      chickens.
AB  - 1. Nitrogen-corrected apparent metabolisable energy (AME[n]) values of 2 diets
      with different energy:protein ratio were estimated in an experiment with 8 groups
      of female and 8 of male chickens in 15 sequential 3-day balance periods from the
      12th to the 56th d of age. 2. The effect of sex on AME(n) values was not
      significant. 3. The effect of age was highly significant. AME(n) values of the
      mixture with the narrower energy:protein ratio increased with age. The dependence
      of AME(n) of the diet with the wider energy:protein ratio on age was parabolic,
      AME(n) values increasing only until the 37th day of life. 4. Under conditions of
      ad libitum feeding, AME(n) of the mixture with the wider energy:protein ratio
      given to female chickens decreased significantly with increasing food intake.

PMID- 9280357
TI  - Compensatory growth of broiler chickens is associated with an enhanced pulsatile
      growth hormone (GH) secretion: preferential amplification of GH secretory burst
      mass.
AB  - 1. The present study was conducted to establish the effect of compensatory growth
      of broiler chickens on pulsatile growth hormone (GH) secretion. 2. Exposing male
      broiler chickens to intermittent lighting (IL) at 10 d of age was associated with
      a transient reduction in body weight gain which was followed by compensatory
      growth from 4 weeks of age onwards. At 34 d of age, cannulated IL broiler
      chickens manifesting compensatory growth and control chickens reared under
      continuous illumination (CL) were serially sampled at 10 min intervals over 5
      consecutive hours and plasma GH concentrations measured. The resultant GH time
      series were analysed by deconvolution analysis. 3. The overall mean GH
      concentration was higher for IL than for CL broilers. The burst frequency did not
      differ between lighting treatments, but during each GH surge, IL broilers
      released a higher GH mass which resulted in higher GH amplitude values. As a
      consequence, GH production rates of IL broilers during the entire sampling
      session were markedly elevated compared to those of their age-matched CL
      broilers. There were no differences in the monoexponential GH half-life. 4.
      Compensatory growth in broiler chickens is associated with an amplification of GH
      secretory burst mass. The underlying causal mechanisms remain to be elucidated.

PMID- 9280356
TI  - Ileal amino acid digestibility assay for the growing meat chicken--effect of the
      imposition of a fasting period and the nature of the test diet.
AB  - 1. The objective of this study was to investigate the effects of cold-pelleting,
      the length of the fasting period before feeding of the test diet and the nature
      of the test diet on apparent ileal nitrogen (N) digestibility in the broiler
      chicken. 2. Four-week-old broiler chickens were given a pelleted or non-pelleted
      maize/soyabean meal (basal) diet. The birds were starved for 24 h, given a single
      test meal (25 g) by intubation and killed 4 h after the start of feeding by
      administration of a barbiturate, to allow sampling of ileal digesta (terminal 15
      cm). Cold-pelleting did not affect apparent ileal N digestibility. 3. Four-week
      old broiler chickens were fasted for 12 or 24 h and then received a test meal (1
      h free access) of either a pelleted soyabean meal or a pelleted meat-and-bone
      meal diet or were continuously fed on one of the two diets. The imposition of a
      fast did not affect apparent ileal N digestibility. However, a 24 h fasting
      procedure was preferred, as the between animal variation for apparent ileal N
      digestibility was lower than for the 12 h fast or for continuous feeding. 4. Four
      week-old broiler chickens were given either semi-synthetic starch-based diets
      containing maize, wheat bran, meat-and-bone meal or fish meal as the sole sources
      of protein or each of these diets in combination with the basal diet (50:50 on a
      dry matter basis). With the exception of the maize diet, the apparent ileal N
      digestibility values calculated by correcting for the digestibility of the basal
      dietary component were significantly lower than when digestibility was determined
      directly using a diet in which the respective proteins were the sole protein
      source. This implies that interactions between the dietary ingredients influence
      estimates of apparent ileal N digestibility.

PMID- 9280358
TI  - Effect of novelty and restraint on catecholamines in plasma of laying hens.
AB  - 1. The present study describes the effects of novelty (experiment 1) and
      restraint (experiment 2) on the catecholamine responses in laying hens. 2. Manual
      restraint caused a higher catecholamine response than mere visual exposure to a
      human being wearing yellow gloves and swinging his hand in the bird's home cage.
      3. A relationship could be shown between adrenaline concentrations in plasma
      after a novel stimulus and the duration of tonic immobility.

PMID- 9280359
TI  - Effects of early heat exposure on thermoregulatory responses and blood viscosity
      of broilers prior to marketing.
AB  - 1. This study was to determine the effects of heat load early in life on
      thermoregulatory responses and whole blood viscosity of broilers during a
      subsequent exposure to high environmental temperature later in life. 2. The
      birds, which had been subjected to exposure to 38 degrees C for 24 h at 5-d-old,
      served as prior exposure group (group A). Both group A and control group B were
      exposed to 33 degrees C for 3 h when near marketable weight. 3. On exposure to 33
      degrees C, although there were no significant differences in the increases in
      heat production (HP) between the two groups, abdominal temperature (Ta),
      temperature of external ear tract (Tee), shank skin temperature (Tss), standing
      lying frequency and lying time were lower in group A than in group B. Heart rate
      (HR) and comb surface temperature (Tcs) did not differ but increased in both
      groups during exposure to 33 degrees C. Respiration rate (RR) was greater in
      group A. 4. Blood viscosity decreased markedly in both groups after exposure to
      33 degrees C; the decrease was greater in group A. 5. These results suggest that
      early exposure may promote broilers' ability to cope with the subsequent heat
      load by altering thermoregulatory physiological responses and behavioural
      patterns, resulting in an alleviation of heat stress.

PMID- 9280360
TI  - Transport of L-valine by the chicken caecum.
AB  - 1. We have studied L-valine transport by the caecal segments of 6- to 8-week-old
      chickens. Isolated enterocytes from the proximal caecum incubated with 0.1 mM L
      valine can accumulate the substrate against a concentration gradient. After 50
      min incubation, the intracellular L-valine concentration reached 0.53 mM, a value
      higher than that observed in enterocytes from the jejunum (0.34 mM; P< 0.01). 2.
      Enterocytes from the medial and distal caccal regions are unable to transport L
      valine uphill (cell concentration: 0.1 mM). 3. Amino acid accumulation by
      proximal caecal cells was Na+ -dependent and was inhibited by ouabain and 2,4
      dinitrophenol. L-methionine inhibits L-valine uptake and a 2.5 mM concentration
      abolishes the capacity of enterocytes to accumulate the substrate. 4. The high
      accumulation ratios shown by the proximal caecum for L-valine suggest a role for
      this intestinal segment in the absorption of neutral amino acids present in the
      caecal chamber.

PMID- 9280361
TI  - A comparative study between mature ostriches (Struthio camelus) and adult
      cockerels with regard to the true and apparent digestibilities of amino acids.
AB  - 1. A study was conducted to compare apparent and true digestibility of amino
      acids in a high protein experimental diet between young ostriches (7 months of
      age) and cockerels. 2. A mean value for true digestibility of amino acids (TAAD)
      of 0.837 +/- 0.0073 (range 0.780 to 0.862) was derived for ostriches, compared
      with a mean value of 0.795 +/- 0.0258 (range 0.723 to 0.825) for cockerels. 3.
      True retention of dietary protein was 0.646 +/- 0.0114 and 0.609 +/- 0.0643 for
      ostriches and cockerels respectively. 4. Results in the present study produced
      evidence that the method for determining metabolisable energy values of
      ingredients for ostriches is also suitable for measuring the digestibility of
      amino acids. 5. It was concluded that accurate diet formulation for ostriches
      requires the assessment of amino acid digestibilities for individual ingredients,
      because values derived from poultry would underestimate digestibilities for
      ostriches.

PMID- 9280362
TI  - Growth rate of different sexes of the European quail (Coturnix coturnix).
AB  - 1. The Gompertz equation was used to described the growth of the European quail
      (Coturnix coturnix) from hatching until 107 d of age. 2. Differences (P< 0.05) in
      growth existed between sexes. Mature mass values of 148.0 +/- 3.00 and 191.9 +/-
      5.35 g respectively were found for males and females. Males reached maximum
      growth at 13.4 +/- 0.33 d while a value of 16.4 +/- 0.46 d was found for females.
      3. A plateau in daily food intake was reached when the time of mature mass was
      approached.

PMID- 9280363
TI  - Pharmacokinetics of flumequine in sheep after intravenous and intramuscular
      administration: bioavailability and tissue residue studies.
AB  - The pharmacokinetic properties of flumequine and its metabolite 7
      hydroxyflumequine were determined in six healthy sheep after single intramuscular
      (i.m.) and intravenous (i.v) injections at a dose of 6 mg/kg body weight. The
      tissue residues were determined in 20 healthy sheep after repeated i.m.
      administration with a first dose of 12 mg/kg and nine doses of 6 mg/kg. The
      flumequine formulation used was Flumiquil 3% Suspension Injectable. The mean
      plasma concentrations of flumequine after i.v. administration were described by a
      three-compartment open model with a rapid distribution and a relatively slow
      elimination phase. The low value of volume of distribution at steady state (Vdss)
      (0.52 +/- 0.24 L/kg) and high value of volume of distribution (Vdlambda3) (5.05
      +/- 3.47 L/kg) emphasized the existence of a small compartment with a slow rate
      of return to the central compartment. The mean elimination half-life was 11.5 h.
      The 7-hydroxyflumequine plasma levels represented 2.3% of the total area under
      the curve. The mean plasma concentrations of flumequine after i.m. administration
      were characteristic of a two-compartment model with a first order absorption. The
      mean maximal plasma concentration (1.83 +/- 1.15 microg/mL) was obtained rapidly,
      i.e. 1.39 +/- 0.71 h after the i.m. administration. The fraction of dose absorbed
      from the injection site was 85.00 +/- 30.13%. The minimal concentrations of
      flumequine during repeated treatment were significantly lower in females than in
      males. Eighteen hours after the last repeated i.m. administration, the highest
      concentration of flumequine was observed at the injection sites followed by
      kidney, liver, muscle and fat. The highest concentration of 7-hydroxyflumequine
      was observed in the kidney and was ten times lower than the flumequine
      concentration. The longest flumequine elimination half-life was observed in the
      fat.

PMID- 9280364
TI  - Pharmacokinetics of penicillin-G in ewes and cows in late pregnancy and in early
      lactation.
AB  - Concentrations of penicillin-G in serum were determined after single intravenous
      doses of potassium penicillin-G (10 mg/kg body wt) to ewes and cows in late
      pregnancy and in early lactation. Penicillin-G in serum was analysed by a
      microbiological method and pharmacokinetic parameters were calculated by model
      independent methods. Serum concentrations were lower in early lactation than in
      late pregnancy in both ewes and cows. The differences were statistically
      significant at most sampling times in ewes but only during the first hour in
      cows. Weight corrected values of clearance and volume of distribution were
      significantly higher in early lactation than in late pregnancy in both ewes and
      cows. Mean residence time and elimination-half life were shorter in lactating
      than in pregnant ewes, however for the latter parameter the difference was not
      statistically significant. Neither of these parameters changed in cows. It is
      concluded that in both ewes and cows pharmacokinetic parameters of penicillin-G
      are altered from late pregnancy to early lactation but that these changes have
      little practical impact and do not call for a revised dosage regime of the
      studied drug.

PMID- 9280365
TI  - Comparative pharmacokinetics of ampicillin trihydrate, gentamicin sulphate and
      oxytetracycline hydrochloride in Nubian goats and desert sheep.
AB  - In this investigation the pharmacokinetics of three commonly used antibiotics,
      ampicillin trihydrate (10 mg/kg), gentamicin sulphate (3 mg/kg) and
      oxytetracycline hydrochloride (5 mg/kg), given intravenously, were each studied
      in five Nubian goats and five desert sheep. The pharmacokinetic parameters were
      described by a two-compartment open model. The results indicated that there were
      significant differences between the two species in some kinetic parameters of
      ampicillin and oxytetracycline but not gentamicin. Ampicillin elimination half
      life (t[1/2beta]) in goats (1.20 h) was shorter than that in sheep (2.48 h), and
      its clearance (Cl) significantly higher in goats (2921 mL/h x kg) compared to
      sheep (262 mL/h x kg) (P < 0.01). Ampicillin volume of distribution (Vd[area])
      was found to be significantly larger in goats (5673 mL/kg) than in sheep (992
      mL/kg) (P < 0.01). For oxytetracycline, the t(1/2beta) in goats (3.89 h) was
      significantly shorter than that in sheep (6.30 h) and the Cl value in goats (437
      mL/h x kg) was significantly higher than in sheep (281 mL/h x kg). The results
      suggest that when treating sheep and goats, the pharmacokinetic differences
      between the two species must be considered in order to optimize the therapeutic
      doses of ampicillin and oxytetracycline.

PMID- 9280366
TI  - Pharmacokinetics of oxolinic acid in sea-bass, Dicentrarchus labrax (L., 1758),
      after a single rapid intravascular injection.
AB  - The pharmacokinetics of oxolinic acid was studied in sea-bass (Dicentrarchus
      labrax). The fish were kept in seawater at 15.2 degrees C with a 12 h/12 h
      photoperiod. Oxolinic acid was injected in the caudal vein of anaesthetized sea
      bass in a single rapid intravascular administration at a dose of 10 mg/kg of body
      weight. Plasma concentrations of oxolinic acid were determined using two
      analytical methods, a classic plate diffusion bioassay using Escherichia coli and
      a high performance liquid chromatography (HPLC) using solid phase extraction with
      an internal standard and a U.V. detection. The mean recoveries were 99.6% and
      110.8% and determination limits were 0.04 microg/mL and 0.02 microg/mL, for the
      bioassay and the HPLC respectively. Compared to other fish species, the oxolinic
      acid was rapidly (absorption half life, t(a1/2) = 0.69 h) distributed to body
      tissues outside the blood volume (volume of central compartment, Vc = 0.4 L/kg)
      and presented a large volume of distribution (Vdss = 2.55 L/kg). Considering its
      disappearance from the central compartment (rate constant: central-eliminated,
      k10 = 0.16 h[-1]) and its total body clearance (Cl[t] = 0.066 L/kg x h), the
      elimination phase of the oxolinic acid in sea-bass was shorter than in trout kept
      in freshwater, and longer than in salmon in seawater. Consequently, the area
      under the concentration-time curve (AUC = 157 microg x h/mL) and the mean
      residence time (MRT = 42 h) were relatively low and short, respectively.

PMID- 9280367
TI  - Structure-activity relationships between antibacterial activities and
      physicochemical properties of sulfonamides.
AB  - Relationships between the antimicrobial activities of sulfonamides and
      physicochemical properties including the acid dissociation constant (pKa) and the
      hydrophobicity constant (pi) were determined. The minimal inhibitory
      concentrations (MIC) of sulfonamides against Actinobacillus pleuropneumoniae, a
      gram-negative veterinary pathogen, were used. High performance liquid
      chromatography was applied for the determination of the electronic and
      hydrophobic parameters. Empirically determined relationships pointed out the
      dominant role of the degree of ionization on the antimicrobial activity. The data
      indicate that hydrophobic properties of sulfonamides, characterized by pi, are of
      minor importance for the in vitro antibacterial activity. Because of the
      restricted pKa range (4.9-7.7) it could not be established whether the
      relationship between pKa and activity was linear or bilinear. Whenever o,m
      disubstituted sulfonamides were included correlations decreased substantially.
      Relationships based on multicompartment equilibrium models were derived and
      indicated a bilinear relation between pKa and MIC. Model-based equations showed
      that the antibacterial activity was governed by the extracellular ionic
      concentration of the sulfonamides whenever different intra and extracellular pH
      values were assumed in the equilibrium model. The antimicrobial activities of the
      sulfonamides against gram-positive organisms were also related to the degree of
      ionization of the sulfonamides in the agar medium.

PMID- 9280368
TI  - A comparison of preoperative morphine and buprenorphine for postoperative
      analgesia for arthrotomy in dogs.
AB  - The aim of this study was to compare morphine with the partial agonist,
      buprenorphine, for postoperative analgesic effects, when administered
      preoperatively for elective arthrotomy in dogs. Fifty two dogs were anaesthetized
      for stifle, elbow, or hock arthrotomy. The dogs were premedicated 30 min prior to
      induction of anaesthesia with 0.03 mg/kg acepromazine intramuscularly, and either
      0.3 mg/kg morphine or 0.01 mg/kg buprenorphine intramuscularly (allocated
      randomly). Anaesthesia was induced with thiopentone and maintained with halothane
      in an oxygen/nitrous oxide mixture. Pain and sedation were assessed
      preoperatively, and 0.5, 1, 2, 3, 5, and 7 h after the halothane was switched
      off, with a visual analogue scale scoring system. Pain scores did not differ
      significantly (morphine group median postoperative score from 30 to 40 mm,
      buprenophine group median postoperative score from 36 to 43 mm) and analgesia was
      considered adequate in the majority of cases (score less than 40 mm). Morphine
      produced significantly more sedation at 0.5 h after anaesthesia only. It was
      concluded that both opioids are equally suitable analgesics for postoperative
      analgesia for the elective arthrotomy in dogs.

PMID- 9280369
TI  - The effects of medetomidine and xylazine on gastrointestinal motility and gastrin
      release in the dog.
AB  - The effect of medetomidine, a potent and highly selective alpha2-adrenoceptor
      agonist, on the motility of the gastric antrum, duodenum, mid-jejunum and ileum
      was investigated in ten dogs. Its effect on the release of gastrin was also
      determined. Administration of medetomidine intramuscularly (i.m.) at a dose of 40
      microg/kg inhibited the motility of the gastric antrum, duodenum, mid-jejunum and
      ileum significantly, in comparison to administration of xylazine intramuscularly
      at a dose of 2.0 mg/kg. The release of gastrin was also significantly decreased
      in dogs receiving medetomidine. It was found to inhibit the motility in the
      gastric antrum and duodenum longer than in the mid-jejunum and ileum, presumably
      by acting specifically on alpha2-adrenoceptors, likely at the peripheral level.
      Medetomidine also inhibited the gastric contraction associated with gastrin
      secretion.

PMID- 9280370
TI  - Pharmacology of the 5-lipoxygenase inhibitors BAY Y 1015 and BAY X 1005 in the
      horse.
AB  - Calcium ionophore A23187 induced time and concentration dependent production of
      immunoreactive leukotriene (LT) B4 by equine heparinized whole blood in vitro.
      Time dependent production of immunoreactive LTB4 by equine neutrophils and
      immunoreactive LTC4 by equine eosinophils in vitro was also demonstrated. The 5
      lipoxygenase activating protein (FLAP) inhibitors, BAY X 1005 and BAY Y 1015,
      produced concentration dependent inhibition of ionophore-induced LTB4 synthesis
      by equine whole blood (mean +/- SEM IC50s n = 5; 6.14 +/- 0.28 microM vs. 12.30
      +/- 0.75 microM for BAY Y 1015 and BAY X 1005, respectively) and neutrophils
      (mean +/- SEM IC50s n = 5; 0.003 +/- 0.001 microM vs. 0.045 +/- 0.021 microM for
      BAY Y 1015 and BAY X 1005, respectively) and LTC4 synthesis by equine eosinophils
      (mean +/- SEM IC50s n = 5; 0.0036 +/- 0.0002 microM and 0.108 +/- 0.023 microM
      for BAY Y 1015 and BAY X 1005, respectively) in vitro. In all three assays, BAY Y
      1015 was more potent than BAY X 1005, and for both compounds much higher
      concentrations were required to inhibit LT synthesis by whole blood compared to
      isolated neutrophils and eosinophils. Plasma concentration-time relationships and
      pharmacokinetic parameters for BAY Y 1015 administered intravenously and orally
      to six horses at a dosage of 10 mg/kg in a two period cross-over study were
      established. The study also evaluated the anti-inflammatory properties of BAY Y
      1015 and its ability to inhibit ex vivo whole blood LTB4 synthesis and in vivo
      LTB4 synthesis in a tissue cage model of acute inflammation. At this dosage, BAY
      Y 1015 failed to significantly inhibit immunoreactive LTB4 synthesis or the
      oedema produced by intradermal injection of the mild irritant, carrageenan.

PMID- 9280371
TI  - Alpha-adrenoceptors in equine digital veins: evidence for the presence of both
      alpha1 and alpha2-receptors mediating vasoconstriction.
AB  - Rings of equine digital vein examined under conditions of isometric tension
      recording constricted to alpha-adrenoceptor agonists with an order of potency of
      5-bromo-6-[2-imidazolin-2-yl-amino]-quinoxaline bitartrate (UK 14304) =
      noradrenaline > 6-Allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-(4,5-d) azepine
      (BHT-920) > phenylephrine > dopamine > methoxamine. The maximum force generated
      was greatest for the non-selective agonist noradrenaline and lowest for the
      alpha2-selective agonist BHT-920 with the other agonists between these two
      extremes. Selective inactivation of alpha1-adrenoceptors (achieved by treating
      yohimbine-protected tissues with phenoxybenzamine) reduced the maximum responses
      of all agonists, the EC50 values of UK 14304, BHT-920 and noradrenaline and
      increased the EC50 values of phenylephrine and methoxamine. Prazosin (30 nM) had
      no inhibitory effect on responses to low concentrations of BHT-920 and UK 14304
      and caused competitive inhibition of responses to phenylephrine and noradrenaline
      giving pKb values of 8.49 +/- 0.18 and 8.23 +/- 0.14, respectively. Yohimbine
      (0.1 microM) caused significant competitive inhibition of responses to BHT-920
      and noradrenaline with calculated pKb values of 8.43 +/- 0.11 for BHT-920 and
      7.43 +/- 0.31 for noradrenaline and non-competitive inhibition of responses to UK
      14304. 2-[2-methoxy-1,4-benzodioxan-2-yl]-2-imidazoline (RX 821002; 10 nM) caused
      competitive inhibition of responses to BHT-920 (pKb 9.04 +/- 0.27) and dopamine
      (pKb 8.2 +/- 0.2). These data indicate that equine digital veins possess both
      post-synaptic alpha1 and alpha2-adrenoceptors.

PMID- 9280372
TI  - Pharmacokinetics of ampicillin and sulfadimidine in pigs infected experimentally
      with Streptococcus suum.
AB  - Twenty-three hybrid pigs (23 +/- 3 kg body wt) were assigned to three groups to
      investigate the pharmacokinetics of ampicillin (APC, 10 mg/kg) administered
      intravenously (i.v.) and intramuscularly (i.m.), and sulfadimidine (SDM, 50
      mg/kg) administered intravenously as a bolus injection. In the first series of
      experiments the animals remained healthy. Subsequently, the pigs were infected
      with Streptococcus suum by subcutaneous (s.c.) inoculation and the experiments
      were repeated. The total apparent distribution volume of APC given intravenously
      was increased from 0.512 +/- 0.026 L/kg in uninfected pigs to 0.68 +/- 0.06 L/kg
      (P < 0.01) in infected pigs, whereas there were no significant changes in the
      same parameter for SDM (P > 0.05). The clearance of APC was increased markedly
      from 0.52 +/- 0.07 L/kg/h in uninfected pigs to 0.62 +/- 0.10 L/kg/h in infected
      pigs. In contrast, SDM clearance was decreased markedly from 0.023 +/- 0.003
      L/kg/h to 0.017 +/- 0.003 L/kg/h (P < 0.05). As a result, the biological half
      lives of the drugs were altered to varying degrees in infected pigs. The half
      life of SDM was increased from 15.0 +/- 3.0 h in uninfected pigs to 20 +/- 7h in
      infected pigs (P < 0.05), but differences in APC half-lives between uninfected
      and infected animals were not observed (P > 0.05). There were no statistically
      significant differences in pharmacokinetic parameters of APC administered by
      intramuscular injection between the healthy and the diseased status, although its
      half-life was shortened from 0.76 +/- 0.22 h in the healthy to 0.57 +/- 0.23 h in
      the diseased. The results suggest that blood concentrations of APC and SDM are
      affected differently by the same disease due to its specific effects on their
      distribution and elimination.

PMID- 9280373
TI  - Effect of cisapride on myoelectrical activity of the antrum pylori in the
      conscious miniature pig.

PMID- 9280374
TI  - Pharmacokinetics of ciprofloxacin following intravenous and oral administration
      in broiler chickens.

PMID- 9280375
TI  - Disposition of flunixin after intramuscular administration of flunixin meglumine
      to horses.

PMID- 9280376
TI  - Commentary: gender, disability, and abuse.

PMID- 9280377
TI  - Gender differences in abused children with and without disabilities.
AB  - OBJECTIVE: Two questions were posed: (1) What are the proportions of boys and
      girls in various categories of substantiated child abuse? (2) Do the gender
      proportions differ for children with and without disabilities? METHOD: Data
      collected by previous researchers from a demographically representative sample of
      U.S. child abuse reporting districts was analyzed. This included 1,249 case files
      involving 1,834 children. The number of girls and boys who did and did not have
      disabilities was identified for three age categories and for several categories
      of abuse. Chi-square analyses were used to determine whether there was a
      relationship between disability and gender for the various age and abuse
      categories. RESULTS: More boys were physically abused and neglected, but more
      girls were sexually abused. Boys with disabilities, however, were over
      represented in all categories of abuse. Moreover, gender proportions among abused
      children with disabilities differed significantly from those found among other
      abused children. Although slightly more than half of abused children without
      disabilities were girls, 65% of abused children with disabilities were boys.
      CONCLUSIONS: Boys represented a significantly larger proportion of physically
      abused, sexually abused, and neglected children with disabilities than would be
      expected from their respective proportion of abused and neglected children
      without disabilities. Several possible explanations for the observed gender and
      disability status interaction are discussed.

PMID- 9280378
TI  - The prediction of child maltreatment in Greek families.
AB  - OBJECTIVE: The study had two aims: First, to identify characteristics of
      physically maltreating families in the Attica region of Greece; and second, to
      produce a checklist of high risk predictors which may be used for screening, as
      an assessment, to enable secondary prevention of physical abuse and neglect.
      METHOD: A case control design was used with individual matching. The sample
      comprised 197 physically abused and neglected children and their families
      referred to a multidisciplinary team. These were compared with 163 control
      children and their families attending a community health center. RESULTS: The
      findings suggest that abusing families differ from controls on a number of
      variables related to child, parental, and family characteristics. The statistical
      analysis produced a checklist of 15 Predictors. Their classification into High,
      Medium, and Low Predictors pointed out that the most prominent characteristics
      were those associated with parents' own adverse life experiences, mental health
      problems, bad quality of relationship between spouses, and parental neglect of
      the child's hygiene. The predictive ability of the checklist produced a
      sensitivity of 92% and a specificity of 96% (logistic regression) and a
      sensitivity of 86.8% and a specificity of 96.3% (discriminant function). The use
      of this checklist for screening is discussed with emphasis on methodological and
      ethical issues. Special emphasis is given on the cultural relevance of such an
      application within the Greek cultural milieu. CONCLUSION: The findings indicate
      that secondary prevention of child maltreatment in Greece is feasible by using a
      checklist of risk factors as predictors. Such screening should be accompanied by
      clinical assessment based on qualitative aspects of mother-infant interaction.
      Special emphasis should be given to the cultural relevance of this approach while
      ethical issues should be considered.

PMID- 9280379
TI  - The impact of war on the mental health of children: a Salvadoran study.
AB  - OBJECTIVE: This ecologically conceptualized, intensive study assesses the mental
      health impact of the Salvadoran Civil War on 54 12-year-olds, born into the war,
      exposed to different levels of war violence. METHODS: Half of the students came
      from a repopulated country village and half from an industrial neighborhood near
      the capital city. Children, their mothers or caretakers, and their teachers
      responded to interviews and some instruments. RESULTS: Children from the
      repopulated village reported higher war experience and lower mental health. The
      personal/social impact of the war was more important than family togetherness or
      war intensity in determining the mental health of the children. Children's
      intelligence was highly related to surviving with higher mental health. Higher
      socioeconomic status (SES) and education of parents was related to better mental
      health. Controlling for intelligence, children who experienced the highest
      personal-social impact of war showed the poorest mental health. Children with
      high war experience were most likely to have difficulty in imagining the future.
      CONCLUSIONS: Intelligence and the foreshortening of future vision are variables
      that should be controlled for and investigated in outcome studies of trauma.
      Treatment for survivors should include aid in planning for the future.

PMID- 9280380
TI  - Outcome and cost of child abuse.
AB  - OBJECTIVE: To compare the cases of child abuse (CA) with other admissions in a
      pediatric intensive care unit (PICU) for differences in patient-specific health
      care costs, severity of illness (SI) and mortality, and describe their outcome.
      METHOD: A retrospective cohort study of all patients admitted to the PICU between
      January 1991 and August 1994. Discharge diagnosis, age, SI, mortality rate,
      length of stay, hospitalization charges ($Hosp), and mortality were retrieved.
      RESULTS: There were 937 admissions; 13 were secondary to CA. Cases of CA
      represented 1.4% of admissions and 17% of deaths. CA patients had the highest SI
      (61%), $Hosp ($30,684), daily charges ($5,294) and mortality rates (53%) than any
      other group. In our patients, SI is a factor that affects charges. Even when
      compared to a cohort group with SI, child abuse patients had higher daily
      hospitalization charges (p < .05). The medical bills for the acute care of a CA
      patient averaged $35,641 per case. Even with these expenditures, 70% died and 60%
      of the survivors had severe residual morbidity. CONCLUSION: These results confirm
      that interventional medical care in response to severe CA is very costly and the
      ultimate outcome is significantly worse than other diseases. Therefore, we
      believe it is imperative to allocate resources to prevention.

PMID- 9280381
TI  - Victims of child abuse and neglect in the U.S. Army.
AB  - OBJECTIVE: The two main objectives of the study were: (1) to contrast child
      maltreatment victim rates in U.S. Army and civilian populations; (2) to identify
      the demographic characteristics of Army children at increased risk for the
      following types of child maltreatment: major physical abuse, minor physical
      abuse, emotional maltreatment, sexual maltreatment, and neglect. METHOD: This
      study presents a descriptive analysis of child maltreatment victims in the United
      States Army during the years 1992 and 1993. Data on all substantiated child
      maltreatment cases in the Army Family Advocacy Central Registry were obtained
      from the Army Medical Department's Patient Administration System and
      Biostatistics Activity. Rates of abuse for demographic subsets of the population
      were calculated and compared. RESULTS: Major findings include the following: The
      overall rate of child maltreatment appears to be lower in the Army than in the
      general population. Rates of neglect were markedly lower in the Army population.
      Young children and children with lower ranking sponsors were at greatest risk for
      major physical abuse and neglect. Boys were neglect victims more frequently than
      girls. Teenage girls were the highest risk group for minor physical abuse,
      emotional abuse, and sexual abuse. At younger ages, boys had greater risk of
      minor physical abuse, while girls again had greater risk of sexual abuse.
      CONCLUSIONS: The Department of the Army sponsors an extensive program of child
      abuse prevention initiatives. This program may be strengthened by emphasizing
      prevention services to the identified high risk groups.

PMID- 9280382
TI  - Prevalence, characteristics, and impact of childhood sexual abuse in a
      Southwestern American Indian tribe.
AB  - OBJECTIVE: There were two objectives; first, to investigate the prevalence and
      characteristics of child sexual abuse in an American Indian community, and
      second, to determine whether persons with histories of child sexual abuse are at
      greater risk to develop psychiatric disorders and behavioral problems than
      persons who report no such history. METHOD: A sample of 582 Southwestern American
      Indian tribal members was collected for a genetic and linkage study on alcoholism
      and psychiatric disorders in three large and interrelated pedigrees. Subjects
      were recruited from the community without knowledge of their clinical histories
      or those of their relatives. Child sexual abuse and psychiatric disorders were
      assessed using a semi-structured psychiatric interview. RESULTS: Females were
      more likely to be sexually abused as children (49%) than were males (14%).
      Intrafamilial members accounted for 78% of the reported child sexual abuse.
      Sexually abused males and females were more likely to report childhood and adult
      behavioral problems than were nonabused subjects. There was a strong relationship
      between multiple psychiatric disorders and child sexual abuse, with sexually
      abused males and females more likely to be diagnosed with > or = 3 psychiatric
      disorders, both including and excluding alcohol dependence or abuse, than were
      nonabused subjects. CONCLUSION: Child sexual abuse in this population is both an
      index of family dysfunction and community disorganization as well as a predictor
      of later behavioral patterns and psychopathology.

PMID- 9280383
TI  - Childhood sexual abuse, adolescent sexual behaviors and sexual revictimization.
AB  - OBJECTIVE: The aims of this study were to examine the extent to which exposure to
      childhood sexual abuse (CSA) was associated with increased rates of sexual risk
      taking behaviors and sexual revictimization during adolescence. METHOD: A birth
      cohort of 520 New Zealand born young women was studied at regular intervals from
      birth to the age of 18. At age 18 retrospective reports of CSA were obtained from
      sample members. Over the course of the 18 year study information was gathered on:
      (a) childhood, family, and related circumstances; and (b) the young women's
      history of sexual experiences from 14 to 18 years. RESULTS: Young women reporting
      CSA, and particularly severe CSA involving intercourse, had significantly higher
      rates of early onset consensual sexual activity, teenage pregnancy, multiple
      sexual partners, unprotected intercourse, sexually transmitted disease, and
      sexual assault after the age of 16. Logistic regression analyses suggested that
      the associations between CSA and sexual outcomes in adolescence arose by two
      routes. First, exposure to CSA was associated with a series of childhood and
      family factors including social disadvantage, family instability, impaired parent
      child relationships, and parental adjustment difficulties that were also
      associated with increased sexual vulnerability in adolescence. Second, there
      appeared to be a causal chain relationship between CSA and sexual experiences in
      which CSA was associated with early onset sexual activity which, in turn, led to
      heightened risks of other adverse outcomes in adolescence. CONCLUSIONS: The
      findings of this study suggest that those exposed to CSA have greater sexual
      vulnerability during adolescence. This appears to arise because: (a) the
      childhood and family factors that are associated with CSA are also associated
      with increased sexual risks during adolescence; and (b) exposure to CSA may
      encourage early onset sexual activity which places those exposed to CSA at
      greater sexual risk over the period of adolescence.

PMID- 9280385
TI  - Recognizing child maltreatment in Bangladesh.

PMID- 9280384
TI  - Teaching personal safety skills to young children: an investigation of age and
      gender across five studies.
AB  - OBJECTIVE: To determine the extent to which preschool-aged boys and girls can
      benefit from instruction in personal safety. METHOD: Data compiled from five
      previous studies were employed. Four hundred and six preschoolers were pretested
      and participated in either the Behavioral Skills Training program (BST; Wurtele,
      1986) or a control program. Children were posttested on skill and knowledge
      gains. RESULTS: Preschoolers who had participated in the BST program demonstrated
      greater knowledge and higher levels of personal safety skills compared with
      controls. Boys and girls reacted similarly to the program, as did children from
      younger and older age groups. CONCLUSIONS: These results provide support for the
      assertion that most preschool-aged children can benefit from participating in a
      developmentally appropriate personal safety program. Suggestions for expanding
      the efforts to prevent child sexual abuse are offered, so that children do not
      shoulder the full responsibility for prevention.

PMID- 9280386
TI  - The immune and inflammatory response to orf virus.
AB  - Orf virus is a zoonotic, epitheliotropic DNA parapox virus that principally
      infects sheep and goats. The fact that the virus can repeatedly reinfect sheep
      has provoked an interest in the underlying cellular, virological and molecular
      mechanisms for its apparent escape from the host protective immune response. The
      local immune and inflammatory response in skin and the cell phenotype and
      cytokine response in lymph analysed around a single lymph node are characteristic
      of an anti-viral response. An unusual feature is the dense accumulation of MHC
      Class II+ dendritic cells in the skin lesion. The function of these cells is not
      known. Orf virus virulence genes and activities have been identified that may
      interfere with the development of the host protective immune and inflammatory
      response.

PMID- 9280387
TI  - Isolation and identification of avian rotavirus from pheasant chicks with signs
      of clinical enteritis.
AB  - Three rotaviruses were isolated from intestinal contents obtained from a flock of
      6-8-day-old pheasant chicks showing diarrhoea and increased mortality. The
      isolates were characterized as avian group A rotavirus by immunoenzymatic
      technique (ELISA) and polyacrylamide gel electrophoresis (PAGE).

PMID- 9280388
TI  - Serogrouping and topotyping of Sudanese and United States strains of epizootic
      hemorrhagic disease virus using PCR.
AB  - The potential use of the recently reported polymerase chain reaction (PCR)
      protocol for detection of United States epizootic hemorrhagic disease virus
      (EHDV) serotype 1 (EHDV-1) and serotype 2 (EHDV-2) ribonucleic acid in cell
      culture and clinical specimens was evaluated for detection of Sudanese EHDV
      strains. EHDV serotype 5 (EHDV-5) and EHDV, isolate 318 (untyped) designated
      (EHDV-318), recovered from sentinel calves at the Khartoum University farm
      (Sudan) were studied. RNA from EHDV-5 and EHDV-318 and a number of EHDV field
      isolates, propagated in cell cultures, were detected by the described PCR-based
      assay. The specific 387 bp PCR products were visualized on ethidium-bromide
      stained agarose gel. Specificity of the PCR products was confirmed by
      chemiluminescent hybridization with non-radiolabeled internal probe.
      Amplification product was not detected when the PCR-based assay was applied to
      RNA from blutongue virus (BTV) prototypes serotypes 2, 10, 11, 13, 16 and 17;
      total nucleic acid extracts from uninfected BHK-21 cells. The results of this
      study indicated that the previously described EHDV-PCR assay could be applied for
      detection of Sudanese as well as United States strains of EHDV serogroup. In
      addition, the described EHDV-PCR assay could be used as a supportive diagnostic
      assay to the current conventional virus isolation procedures used for detection
      of EHDV infection in susceptible ruminants.

PMID- 9280389
TI  - The role of cell-mediated immunity in the pathogenesis of bluetongue virus
      serotype 11 in the experimental infection of vaccine/sensitized calves.
AB  - The cellular immune response of cattle to virulent and avirulent (inactivated)
      bluetongue virus (BTV) was studied. Each of three calves received three
      vaccinations (sensitizations) with binary ethyleneimine (BEI)-inactivated BTV, 3
      weeks apart. The sensitized animals were challenged with BTV-11 strain UC8 3
      weeks after the last vaccination. BTV-seropositive and BTV-seronegative calves
      were used as controls. The animals were bled weekly for virus isolation and for
      evidence of cell-mediated immunity (CMI) as determined by the lymphocyte
      stimulation test (LST). Peripheral blood mononuclear leukocytes (PBM L) cultures
      were induced with purified BTV antigen; the phytomitogens phytohemagglutinin
      (PHA), Concanavalin A (ConA) and pokeweed (PKW) mitogen, and combinations of
      phytomitogens and BTV antigen. LST data were analysed by ANOVA and reported as
      counts per minute (CPM) and stimulation index (SI). Following BTV challenge
      exposure, significant SI to mitogens were found in PBML cultures for all animals.
      BTV antigen induced a weak CMI response. There was evidence of perturbations in
      lymphocyte response as characterised by a sharp decrease in lymphocyte response
      to mitogens following combined BTV-antigen and mitogen PBML induction. The SI
      diminished in PBML cultures after a 4 day incubation period, except for ConA.
      These results provide evidence that the cell-mediated immune response could be
      affected by BTV and that inhibitory mediators might play an important role in the
      pathogenesis of BTV in cattle.

PMID- 9280390
TI  - The polymerase chain reaction for the identification of different species of
      Mycobacterium.
AB  - The polymerase chain reaction (PCR) was performed to identify reference and field
      strains of mycobacteria. PCR was able to identify all the reference strains of
      the Mycobacterium genus and sub-divide them into no Tuberculosis-no Avium
      complex, Tuberculosis complex and, partially, Avium complex. The primers used for
      the last recognised only some strains of the different types of M. avium and M.
      intracellulare. A number of field strains were identified as belonging to the
      Mycobacterium genus, but further research is required for a complete sub-division
      into Tuberculosis complex and Avium complex.

PMID- 9280391
TI  - Monoclonal antibodies to a tumour-associated antigen isolated from circulating
      immune complexes of bovine leukemia virus-infected cattle.
AB  - From circulating immune complexes (ICs) of BLV-infected cattle, an antigen
      preparation was produced that contained some virus-specific proteins and a tumour
      associated antigen. Eleven hybridoma clones were produced that secreted
      monoclonal antibodies (MoAbs) to this tumour-associated antigen, and two of them,
      MoAbs 1B4 and 1E9, were used in further studies. Most antibodies were of IgG1
      subclass and showed no cytotoxic activity towards lymphocytes of BLV-positive
      cattle or to certain tumour cells. The MoAbs 1B4 and 1E9 recognized an antigen of
      about 75 kD on the cell surface of bovine lymphosarcoma cells and circulating
      lymphocytes from BLV-infected cattle with persistent lymphocytosis. The results
      presented indicate that the circulating immune complexes from BLV-positive cattle
      contain a tumour-associated antigen that is expressed on tumour cells and on
      lymphocytes from cattle with persistent lymphocytosis.

PMID- 9280392
TI  - IgG concentration in mammary secretions of goats throughout lactation in healthy
      and coagulase-negative staphylococci infected udders.
AB  - Radial immunodiffusion was used to determine immunoglobulin (Ig)-G concentrations
      in 16 mammary secretions from uninfected udder halves and in 10-14 secretions
      from halves subclinically infected with coagulase-negative staphylococci in goats
      throughout lactation. IgG concentrations in samples from uninfected halves
      decreased rapidly during the first week after parturition (P < 0.001 ),
      henceforth falling slowly up to 30 d post-partum (P < 0.001). From 30 d post
      partum to 180 d of lactation, IgG concentration showed a continuous decline to
      the end of the experiment but these changes were not statistically significant
      until 150 d after kidding (P < 0.01). IgG concentrations in lacteal secretions of
      halves harbouring coagulase-negative staphylococci showed a similar pattern, from
      the first month of lactation, to that observed in healthy udder halves, but
      concentrations were always lower. These differences were significant from 2
      months after parturition (P < 0.001). IgG concentrations were compared with
      somatic cell counts obtained using an automatic counter (Fossomatic).

PMID- 9280393
TI  - Enhancement of the resistance of tilapia and grass carp to experimental Aeromonas
      hydrophila and Edwardsiella tarda infections by several polysaccharides.
AB  - Efficacies of eleven polysaccharides including Bar (glycan extracted from
      Barley), curdlan, Dex (dextran sulfate), inulin, krestin, laminaran, levan, PO
      (glycan extracted from Pleurotus ostreatus), scleroglucan, YG (yeast glucan), and
      zymosan, in the protection of tilapia, Tilapia aureus P., and grass carp,
      Ctenopharyngodon idellus, against bacterial infections in vivo were examined.
      Four glycans. namely, Bar, krestin, scleroglucan, and zymosan were observed to
      significantly increase the survival rates of tilapia (80, 60, 70, and 60%) and
      grass carp (60, 70, 90, and 60%) (p < 0.05) after injection with Aeromonas
      hydrophila. The above mentioned four glycans were also found to raise the
      survival rates of tilapia (70, 60, 80, and 50%) and grass carp (50, 50, 70, and
      50%) (p < 0.05) significantly after infection with Edwardsiella tarda. Moreover,
      Bar, curdlan, krestin, scleroglucan, and zymosan were also found to significantly
      increase the number of NBT-positive staining cells (p < 0.05), which might
      indicate that to activate non-specific phagocytes in fish is one of the
      antibacterial mechanisms of polysaccharides.

PMID- 9280394
TI  - Isolation of verotoxigenic Escherichia coli from the Tasmanian environment.
AB  - Growing concerns on the emergence of verotoxin producing Escherichia coli (VTEC)
      in Australia have focused our attention on the possible sources of VTEC within
      the island state of Tasmania. An analysis of 156 food samples and 194 water
      samples obtained from various areas revealed evidence of eight possible sources.
      Six strains, with serotypes Ont:Hnt, O86:H-, O88:H-, O126:H21 and O134:H-, were
      isolated from water samples. Two VTEC of serotypes Ont:H8, 081:H- were isolated
      from raw meat samples. The waterborne isolates produced verocytotoxin. VT1, while
      both foodborne isolates were strong producers of VT2. Three VTEC isolates
      produced haemolysins, only one produced enterohaemolysin (EntHly) and the
      remaining were reported with alpha-haemolysin (alpha-Hly) activity. An important
      feature in the majority of isolates from water was their lack of ability to
      ferment lactose these isolates are routinely overlooked in public health
      laboratories.

PMID- 9280395
TI  - Interaction of epizootic hemorrhagic disease virus with bovine erythrocytes in
      vitro: electron microscope study.

PMID- 9280396
TI  - Scaling factors to relate drug metabolic clearance in hepatic microsomes,
      isolated hepatocytes, and the intact liver: studies with induced livers involving
      diazepam.
AB  - Microsomal protein recovery and hepatocellularity have been determined and
      investigated as scaling factors for interrelating clearance by hepatic
      microsomes, freshly isolated hepatocytes and whole liver from untreated (UT) rats
      and rats treated with either the cytochrome P450 inducer phenobarbital (PB) or
      dexamethasone (DEX). Hepatocellularity in UT rats (1.1 x 10(8) hepatocytes/g
      liver) was not significantly different after either PB or DEX induction (1.1 and
      1.3 x 10(8) hepatocytes/g liver, respectively). However the microsomal protein
      recovery index, which provides a scaling factor that is inversely related to the
      efficiency of the microsomal preparation procedure, was 47 mg/g liver in both PB
      and DEX microsomes and differs from UT rats (60 mg/g liver). These contrasting
      findings are consistent with the interlaboratory trends in the literature,
      indicating that, although hepatocellularity estimates are in good accord,
      microsomal recovery can vary 2-fold; this has implications for scaling. The
      oxidation of diazepam to its three primary metabolites was measured in PB and DEX
      microsomes and hepatocytes and the scaling factors were applied to these data and
      previously reported UT data. Marked changes in kinetics occur on induction
      resulting in a shift in the major pathway. In particular, 3-hydroxylation is
      induced over 20-fold by DEX. Diazepam CL(int) was determined in vivo after
      administration of a bolus dose into the hepatic portal vein of UT, PB, and DEX
      rats; values of 127, 191, and 323 ml/min/SRW (where SRW is a standard rat weight
      of 250 g), respectively, were obtained. Using these scaling factors, the
      hepatocyte predictions of CL(int) were excellent (99, 144, and 297 ml/min/SRW for
      UT, PB, and DEX, respectively), whereas only the DEX prediction (248 ml/min/SRW)
      was accurate for the microsomal system, with a substantial underprediction for UT
      and PB (46 and 68 ml/min/SRW, respectively). Evidence is presented for product
      inhibition, resulting from accumulation of primary metabolites within the
      microsomal preparation, as the mechanism responsible for this underprediction.
      These results illustrate that the scaling factor approach is applicable to
      induced livers in which both cytochrome P450 complement and zonal distribution
      are altered. These data, together with our previous studies, demonstrate that
      CL(int) in cells (2.4-297 ml/min/SRW), microsomes (2.7-248 ml/min/SRW), and in
      vivo (1.5-323 ml/min/SRW) are related in a linear fashion and hence inherently
      both in vitro systems are of equal value in predicting in vivo CL(int).

PMID- 9280397
TI  - Effects of tauroursodeoxycholate solutions on cyclosporin A bioavailability in
      rats.
AB  - Cyclosporin A (CsA) exhibits poor bioavailability after oral administration of
      Sandimmune, with wide intra- and interindividual variations. Our study sought to
      determine the effect of the coadministration of CsA standard oily formulation and
      tauroursodeoxycholate (TUDC) and that of an aqueous micellar solution containing
      TUDC, monoolein, and CsA in promoting and regulating CsA bioavailability in the
      rat Pharmacokinetic parameters of CsA were determined in fasted rats after either
      an intravenous administration (5 mg/kg) or a single oral CsA dose of 10 mg/kg.
      Compared with oral Sandimmune, the CsA micellar solution significantly improved
      the CsA bioavailability by 160% and decreased the interindividual variability in
      bioavailability expressed as percent coefficient of variation from 32% to 15%.
      The concentration-time profile was modified with a 3.5-fold increase in C(max), a
      reduction of t(max), and an increased trough concentration. Bioavailability
      slightly improved in rats receiving standard oily solution plus concomitant TUDC,
      although not significantly. Data indicate that the structure of the CsA carriers
      greatly affect drug bioavailability and that aqueous micellar solutions of CsA
      TUDC-monoolein constitute efficient vehicles, thus providing for CsA high
      absorption with low variability.

PMID- 9280398
TI  - Pulmonary delivery of intratracheally instilled and aerosolized cyclosporine A to
      young and adult rats.
AB  - The delivery and pharmacokinetics of cyclosporine A (CyA) given locally to the
      airways or iv was evaluated in young and adult rats. After intratracheal (i.t.)
      instillation of saline suspended CyA to adult rats, the CyA plasma levels peaked
      at 30 min with a bioavailability of 78.1 +/- 6.9%. After the i.t. instillation of
      CyA with micelles forming surfactant, Cremophor EL, in adult and young rats, the
      plasma levels peaked at 5 min with a bioavailability of 77.5 +/- 7.2% and 66.3 +/
      4.5%, respectively. The bioavailability of aerosolized CyA was 80.1 +/- 4.1% in
      adults. Thus, CyA is absorbed by the lungs into the systemic circulation of the
      rat in high amounts, independent of age and type of delivery system. Long-term
      treatment with i.t. instillations did not affect body weight gain in young and
      adult rats, and no histopathological changes were found in the lungs. It is
      important to emphasize that CyA plasma clearance in young rats was lower and
      elimination half-life longer than in adults. The slow elimination of CyA in young
      rats indicated profound pharmacokinetic age differences for this species.

PMID- 9280399
TI  - Pharmacokinetics of a potential human cytomegalovirus therapeutic, a
      phosphorothioate oligonucleotide, after intravitreal injection in the rabbit.
AB  - The disposition of ISIS 2922, a phosphorothioate oligonucleotide for treatment of
      cytomegalovirus associated retinitis, was evaluated in rabbits. Vitreous humor
      and retina samples were collected from rabbits that received a single
      intravitreal injection of 66 microg [14C]-labeled ISIS 2922 and were analyzed
      using anion exchange HPLC. Four hr postdosing, the concentration of ISIS 2922 in
      vitreous humor was 3.3 microM. The elimination of ISIS 2922 from the vitreous
      humor exhibited first-order kinetics with a t1/2 of 62 hr. By 10 days postdosing,
      the mean concentration of ISIS 2922 in rabbit vitreous humor had decreased to
      0.17 microM, which represented 22% of the total radioactivity remaining in the
      vitreous. The remaining 78% coeluted on anion exchange HPLC with shorter
      oligonucleotides. In retina, ISIS 2922 accumulated over the first 5 days
      postdosing, reaching a maximum concentration of 3.5 microM, and then declined
      thereafter with an estimated t1/2 of 79 hr. By 10 days postdosing when only 24%
      of the total radioactivity in the retina was parent compound, the concentration
      of ISIS 2922 remained at 1.6 microM, which was 10 times higher than the
      concentration in the vitreous humor. Whereas the elimination of full-length ISIS
      2922 and total radioactivity from the vitreous humor occurred at nearly equal
      rates, ISIS 2922 disappeared more rapidly than did total radioactivity from the
      retina, suggesting a greater role for metabolism in the clearance process from
      retina than the vitreous. Alternatively, the results are consistent with
      metabolites being cleared from the vitreous at approximately the same rate as
      parent compound while in the retina metabolites may be cleared more slowly. The
      data were analyzed with a user-defined pharmacokinetic model, which was then used
      to predict the potential for accumulation of ISIS 2922 during clinical dosing.

PMID- 9280400
TI  - Stability of commercial formulations and aqueous solutions of ifosfamide: a
      reply.
AB  - This study is a reply to a paper in this journal reporting on the chemical
      instability of ifosfamide (IF) (Drug Metab. Dispos. 23, 433-437, 1995). The
      authors describe chloroethylamine as a major degradation product of IF in both
      the powder and aqueous solutions. In the present study, we show that: i) IF
      powder remains pure up to 3-5 years after its expiration date; ii) solutions of
      IF at pH 7 are stable for at least 12 hr at 40 degrees C; and iii) solutions of
      IF at pH 4 or pH 10 are only slightly degraded (approximately 1%) after standing
      for 6 hr at 37 degrees C. We also demonstrate that the reported IF instability
      depends on the analytical procedure used. The trifluoroacetylation procedure used
      by the authors, which is conducted in dichloromethane, led to low derivatization
      yields and to the formation of several degradation compounds of IF, among them
      chloroethylamine. In contrast, when the trifluoroacetylation reaction is
      conducted in ethyl acetate, there is high yield of trifluoroacetylated IF, and
      degradation compounds are minor. In conclusion, we believe that the large amounts
      of chloroethylamine reported by the authors in both powder and aqueous solutions
      of IF stemmed from degradation linked to the method of derivatization. Because IF
      is not readily derivatized by trifluoroacetic anhydride in dichloromethane, the
      combination of heating with possible uncontrolled evaporation of solvent and the
      presence of trifluoroacetic acid in the medium lead to degradation of IF and
      formation of chloroethylamine.

PMID- 9280401
TI  - Orally active inhibitors of human leukocyte elastase. II. Disposition of L
      694,458 in rats and rhesus monkeys.
AB  - The disposition of L-694,458, a potent monocyclic beta-lactam inhibitor of human
      leukocyte elastase, was studied in male Sprague-Dawley rats and rhesus monkeys.
      After iv dosing, L-694,458 exhibited similar pharmacokinetic parameters in rats
      and rhesus monkeys. The mean values for its plasma clearance, terminal half-life,
      and volume of distribution at steady state were 27 ml/min/kg, 1.8 hr, and 4.0
      liters/kg in rats and 34 ml/min/kg, 2.3 hr, and 5 liters/kg in rhesus monkeys.
      The bioavailability of a 10 mg/kg oral dose was higher in rats (65%) than in
      rhesus monkeys (39%). In both species, concentrations of L-694,458 in plasma
      increased more than proportionally when the oral dose was increased from 10 mg/kg
      to 40 mg/kg. In monkeys a protracted plasma concentration-time profile was
      observed at 40 mg/kg, characterized by a delayed T(max) (8-24 hr) and a long
      terminal half-life (6 hr). [3H]L-694,458 was well absorbed after oral dosing to
      rats at 10 mg/kg, as indicated by the high recovery of radioactivity in bile
      (83%) and urine (6%) of bile duct-cannulated rats. Only approximately 5% or less
      of the radioactivity in bile, urine, and feces was a result of intact L-694,458,
      indicating that the compound was being eliminated by metabolism, followed by
      excretion of the metabolites in feces, via bile. Demethylenation of the
      methylenedioxyphenyl group resulting in the catechol was the primary metabolic
      pathway in human and rhesus monkey liver microsomes. In rat liver microsomes, the
      major metabolite was the N-oxide of the methyl-substituted piperazine nitrogen.
      In rats dosed iv and orally with [3H]L-694,458, concentrations of radioactivity
      were highest in the lung (the primary target tissue), adrenals, and liver. L
      694,458 was unstable in rat blood and plasma, degrading via a pathway believed to
      be catalyzed by B-esterases and to involve cleavage of the beta-lactam ring and
      loss of the methylpiperazine phenoxy group. In vitro studies indicated that in
      human liver, L-694,458 was metabolized by CYP3A and 2C isozymes, and in both
      monkey and human liver microsomes the compound acted as an inhibitor of
      testosterone 6beta-hydroxylation.

PMID- 9280402
TI  - Orally active inhibitors of human leukocyte elastase. III. Identification and
      characterization of metabolites of L-694,458 by liquid chromatography-tandem mass
      spectrometry.
AB  - The in vitro and in vivo metabolism of N-[1(R)-(1,3-benzodioxol-5-yl)butyl]-3,3
      diethyl-2(S)-[4-[(4-methy l-1-piperazinyl)carbonyl]phenoxy]-4-oxo-1
      azetidinecarboxamide (L-694,458) was studied in male Sprague-Dawley rats and
      rhesus monkeys. Analysis by LC-MS/MS and NMR revealed that the major metabolite
      generated in incubations with rat liver microsomes resulted from N-oxidation of
      the piperazine group, while the major metabolite generated in monkey liver
      microsomes was the catechol that resulted from O-dealkylation of the
      methylenedioxyphenyl group. Other metabolites observed in these incubations
      include the piperazine N-desmethyl, several monohydroxylated derivatives of the
      parent compound, and three products that resulted from cleavage of the beta
      lactam ring. Incubations of parent compound with rat hepatocytes in culture
      generated two major metabolites that resulted from cleavage of the piperazine
      ring with the loss of an ethylene group from one side of the ring; one of these
      metabolites retained the piperazine N-methyl group, while the other did not. The
      metabolite profiles in vivo were similar to those observed in vitro, but they
      were much more complex owing to secondary and, in some cases, tertiary
      biotransformations of many of the primary metabolites. Bile obtained from orally
      dosed rats contained more than 40 parent-related components, and many of these
      metabolites had arisen from piperazine ring cleavage.

PMID- 9280403
TI  - Characterization of carbamazepine metabolism in a mouse model of carbamazepine
      teratogenicity.
AB  - The disposition of carbamazepine (CBZ) was investigated in the SWV mouse. A 14C
      CBZ dose was administered to CBZ pretreated mice, and the distribution of
      radiolabeled material was determined. Twenty-four hours after the 14C-CBZ dose,
      92.5% of the dose was accounted for in urine (56%), in the visera and carcass
      (22%), in feces (11%), and expired as 14CO2 (2%). CBZ metabolites present in
      hydrolyzed urine were also identified using a combination of spectroscopic
      techniques. CBZ, CBZ-10,11-epoxide (CBZE), 2- and 3-hydroxy-CBZ, methylsulfonyl
      CBZ, and glucuronides of CBZ and CBZE accounted for 64% of total urinary
      radioactivity (0-24 hr) in CBZ pretreated mice. Minor metabolites of CBZ included
      novel cysteine and N-acetylcysteine conjugates of CBZ, as well as a
      methylsulfonyl conjugate of CBZE not previously reported. The urinary excretion
      of these thioether conjugates was increased in CBZ/phenobarbital pretreated mice
      and decreased in CBZ/stiripentol pretreated mice in comparison with CBZ-only
      treated mice. Preliminary studies of the effects of phenobarbital and stiripentol
      on the urinary abundance of these metabolites are consistent with the modulation
      of teratogenicity in the SWV mouse by the same pretreatments. These data suggest
      the formation of thioether metabolites of CBZ may be related to CBZ
      teratogenicity in the SWV mouse.

PMID- 9280404
TI  - Isolation and identification of major urinary metabolites of rifabutin in rats
      and humans.
AB  - The antimycobacterial drug rifabutin is extensively metabolized in humans and
      laboratory animals. About 40% of the dose is excreted in urine as unchanged drug,
      and lipophilic (extractable with 1-chlorobutane) and polar metabolites. Polar
      metabolites accounted for 59.1 +/- 2.5% and 88.8 +/- 4.4% of radioactivity in
      urine collected over 96 hr after intravenous administration of 25 and 1 mg/kg of
      [14C]rifabutin to Sprague-Dawley rats, respectively. After 48 hr, all urinary
      radioactivity consisted of polar metabolites. The most abundant polar metabolite,
      identified by electrospray ionization-MS, collision-induced dissociation-MS, and
      comparison of HPLC retention times with the synthetic standard, was N-isobutyl-4
      hydroxy-piperidine. Lipophilic metabolites accounted for <20% of urinary
      radioactivity. Major lipophilic metabolites, 25-O-deacetyl-rifabutin, 27-O
      demethyl-rifabutin, 31-hydroxy-rifabutin, 32-hydroxy-rifabutin, and 20-hydroxy
      rifabutin were isolated from both human and rat urine by HPLC and identified by
      electrospray ionization-MS, collision-induced dissociation-MS, and NMR
      spectrometry. In addition, two metabolites formed by the oxidation of the N
      isobutyl-piperidyl group of rifabutin were found in the urine of rats, but not
      humans.

PMID- 9280405
TI  - In vitro identification of the human cytochrome P450 enzymes involved in the
      metabolism of R(+)- and S(-)-carvedilol.
AB  - Both the R(+) and the S(-) enantiomers of carvedilol were metabolized in human
      liver microsomes primarily to 4'- (4OHC) and 5'-(5OHC) hydroxyphenyl, 8-hydroxy
      carbazolyl (8OHC) and O-desmethyl (ODMC) derivatives. The S(-) enantiomer was
      metabolized faster than the R(+) enantiomer although the same P450 enzymes seemed
      to be involved in each case. A combination of multivariate correlation analysis,
      the use of selective inhibitors of P450, and microsomes from human lymphoblastoid
      cells expressing various human P450s enabled phenotyping of the enzymes involved
      in the oxidative metabolism of carvedilol. CYP2D6 was primarily responsible for
      4OHC and 5OHC production, although considerable activity was observed in a CYP2D6
      poor metabolizer liver and the variability of these activities across a human
      liver bank was not high. There was some evidence that CYP2E1, CYP2C9, and CYP3A4
      were also involved in the production of these metabolites. CYP1A2 was primarily
      responsible for the 8OHC pathway with additional contributions from CYP3A4. The
      ODMC was clearly associated with CYP2C9 with some evidence for the partial
      involvement of CYP2D6, CYP1A2, and CYP2E1. With its complex P450 phenotype
      pattern and the known contribution of non-oxidative pathways of elimination, the
      activity (or lack of activity) of any particular P450 would have a limited
      influence on the disposition of carvedilol in an individual.

PMID- 9280406
TI  - In vitro and in vivo evaluations of the metabolism, pharmacokinetics, and
      bioavailability of ester prodrugs of L-767,679, a potent fibrinogen receptor
      antagonist: an approach for the selection of a prodrug candidate.
AB  - The present study demonstrates the utility of an in vitro-in vivo correlative
      approach in the selection of an optimum prodrug candidate of L-767,679 (N-([7
      (piperazin-1-yl)-3,4-dihydro-1(1H)-isoquinolinone-2-yl]acetyl)-3(S)-(ethynyl)
      beta-alanine), a potent fibrinogen receptor antagonist. As an initial screening
      step, a comparative in vitro hepatic metabolism study was conducted for L-767,679
      and a series of aliphatic and aromatic ester prodrugs in dogs, monkeys, and
      humans. In all species, the active acid L-767,679, but not the ester prodrugs,
      was resistant to metabolism. Only the methyl, ethyl, and isopropyl esters were
      converted exclusively to the active acid in liver microsomal preparations from
      dogs and humans, and thus were selected for further studies. In the preparations
      from monkeys, all of the esters investigated were metabolized efficiently to both
      the active acid and several other products. The absolute formation rates of L
      767,679 from the esters followed the rank order: methyl approximately ethyl >
      isopropyl in all species, and in humans > dogs for the three esters. The three
      ester prodrugs did not undergo appreciable hydrolysis in blood or upon incubation
      with intestinal S9 from any of the studied species. In vivo evaluation of the
      previous three aliphatic esters in dogs and monkeys supported the in vitro
      findings. L-767,679 was metabolically stable in both dogs and monkeys. After
      intravenous administration of the prodrugs to either species, the extent of acid
      formation was higher in dogs than in monkeys. In addition, the extent of L
      767,679 formed from these prodrugs followed the rank order: methyl approximately
      ethyl > isopropyl. Similar results were obtained after oral dosing of the
      prodrugs, such that the bioavailability of L-767,679 was higher in dogs than in
      monkeys, and the bioavailability was higher after the ethyl ester than after the
      isopropyl prodrug in both species. In either species, both ethyl and isopropyl
      ester prodrugs were better absorbed than L-767,679. Overall, the results
      suggested that the bioavailability of the active acid after administration of an
      ester prodrug was dictated primarily by two factors, viz.:1) the relative rates
      of ester hydrolysis versus competing metabolic reactions and 2) the absolute
      rates of ester hydrolysis. In the case of L-767,679 prodrugs, absorption was not
      a limiting factor. Consequently, the bioavailability of L-767,679 after oral
      administration of the ester prodrugs would likely be greater in humans than in
      dogs, and in humans would be higher with the ethyl ester than with the isopropyl
      ester. On this basis, the ethyl ester was considered as a promising candidate for
      clinical evaluation as a fibrinogen receptor antagonist prodrug.

PMID- 9280408
TI  - Effect of ovariectomy and androgen on phenobarbital induction of hepatic CYP2B1
      and CYP2B2 in Sprague-Dawley rats.
AB  - The purpose of this study was to investigate the impact of prepubertal
      ovariectomy and postpubertal administration of testosterone on inducibility of
      rat hepatic CYP2B1 and CYP2B2 by phenobarbital. Intact adult male and female
      Sprague-Dawley rats were injected ip with sodium phenobarbital (10 mg/kg) or
      saline (control) once daily on days 129-135 of age and sacrificed one day after
      the last dose. Hepatic microsomal androstenedione 16beta-hydroxylase activity,
      benzyloxyresorufin O-dealkylase activity, pentoxyresorufin O-dealkylase activity,
      and CYP2B1 protein levels were lower in phenobarbital-treated female rats than in
      phenobarbital-treated male rats. In contrast, there was no sex difference in
      inducibility of CYP2B2. The lesser inducibility of CYP2B1 in adult female rats
      was attributed to the presence of an intact ovary because prepubertal ovariectomy
      (day 25 of age) resulted in increased induction of CYP2B1 and its associated
      activities (androstenedione 16beta-hydroxylase, benzyloxyresorufin O-dealkylase
      and pentoxyresorufin O-dealkylase) by phenobarbital. By comparison, postpubertal
      administration of testosterone enanthate (5 micromol/kg sc once daily on days 80
      94 of age) did not enhance the inducibility of CYP2B1 or its associated
      activities in prepubertally ovariectomized adult (136-day-old) rats administered
      phenobarbital (10 mg/kg/day on days 129-135 of age). However, the androgen
      treatment did increase CYP2C11-dependent testosterone 2alpha-hydroxylase activity
      in the same microsomal samples. Overall, the results show a sex difference in
      phenobarbital induction of hepatic CYP2B1 but not CYP2B2 in adult Sprague-Dawley
      rats. They also indicate that prepubertal ovariectomy enhances the effect of
      phenobarbital on CYP2B1, whereas administration of testosterone enanthate
      postpubertally does not influence the inducibility of either CYP2B1 or CYP2B2 in
      prepubertally ovariectomized adult rats.

PMID- 9280407
TI  - Human cytochrome P4502B6: interindividual hepatic expression, substrate
      specificity, and role in procarcinogen activation.
AB  - The level of expression and interindividual variation in human hepatic microsomal
      cytochrome P450 (CYP) 2B6 was characterized using a polyclonal antibody (WB-2B6)
      raised against rat CYP2B1. Immunoblot analysis using cDNA-expressed human CYPs
      revealed strong cross-reactivity of this antibody with CYP2B6 (limit of detection
      < 0.05 pmol) and only minor cross-reactivities with human CYP2A6, CYP2D6, and
      CYP2E1, all of which could be resolved from CYP2B6 by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. Analysis of human liver microsomes using this
      antibody revealed immunodetectable CYP2B6 protein in a majority of individual
      liver samples, with levels up to 74 pmol/mg protein in the CYP2B6-positive
      samples. Kinetic analysis of cDNA-expressed CYPs identified many of these enzymes
      as catalysts of 7-ethoxy-4-trifluoromethylcoumarin (7EFC) O-deethylation, but
      with significantly different apparent K(M) values (CYP1A2 < CYP2B6 approximately
      CYP1A1 < CYP2C19 < CYP2C9 < CYP2E1 < CYP2A6). By assaying liver microsomal 7EFC O
      deethylase activity at a low 7EFC concentration (5 microM) and preincubating
      human liver microsomes with anti-CYP1A, anti-CYP2C, and anti-CYP2E1 antibodies,
      we were able to monitor CYP2B6-dependent 7EFC O-deethylase activity in a panel of
      17 human liver microsomes and observe a significant correlation (r2 = 0.80)
      between this activity and CYP2B6 protein content. The ability of CYP2B6 to
      activate prodrugs and procarcinogens was examined using gene locus mutation
      assays in CYP2B6-expressing human lymphoblast cells. CYP2B6-expressing cells were
      found to be more sensitive than control cells to the cytotoxicity and
      mutagenicity of cyclophosphamide, aflatoxin B1, and 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone. CYP2B6 is thus a widely expressed human liver microsomal CYP
      that can contribute to a broad range of drug metabolism and procarcinogen
      activation reactions.

PMID- 9280409
TI  - Characterization of two human flavin-containing monooxygenase (form 3) enzymes
      expressed in Escherichia coli as maltose binding protein fusions.
AB  - To examine the possibility for drug metabolism polymorphism, adult human flavin
      containing monooxygenases (form 3) (EC 1.14.13.8) that differ at one amino acid
      were expressed in Escherichia coli as maltose binding protein fusions. The cDNA
      that was first reported during the cloning of adult human flavin-containing
      monooxygenase was designated the wild type lys158 enzyme. A second cDNA has been
      identified as a common polymorphism in some human populations and was designated
      the glu158 enzyme. The cDNA that encodes both enzymes was subcloned into a high
      yield protein fusion expression system, expressed, and the protein was partially
      purified by affinity chromatography and characterized for enzyme activity with
      selective functional substrate probes. N- and S-oxygenation activity of both
      enzymes was determined with 10-(N,N-dimethylaminopentyl)-2
      (trifluoromethyl)phenothiazine and methyl p-tolyl sulfide, respectively. It was
      found that expression of both lys158 and glu158 enzymes of the human flavin
      containing monooxygenase form 3 as fusions with the maltose binding protein
      resulted in an enzyme that was soluble and greatly stabilized and had a reduced
      requirement for detergent during enzyme purification and during the assay for
      activity. Expression of the fusion proteins has allowed the preparation of stable
      and highly active enzyme at greater purity than was readily possible in the past.
      With the exception of the stability and solubility characteristics, the physical
      and chemical properties of lys158 and glu158 maltose binding fusion proteins of
      human flavin-containing monooxygenase form 3 variants resembled that of flavin
      containing monooxygenase enzyme activity associated with human liver microsomes
      and enzyme isolated from a previous Escherichia coli expression system that
      lacked the protein fusion. Comparison of the catalytic activity of the two fusion
      proteins showed that while both forms were active, there were differences in
      their substrate specificities. Expression of the adult human flavin-containing
      monooxygenase form 3 as a maltose binding protein has allowed considerable
      advances over the previously reported cDNA-expressed enzyme systems and may
      provide the basis for examining the role of the flavin-containing monooxygenase
      in human xenobiotic or drug metabolism.

PMID- 9280410
TI  - Improved separation and immunodetection of rat cytochrome P450 4A forms in liver
      and kidney.
AB  - In the study of tissues that contain several forms of one cytochrome P450
      subfamily, it is useful to develop immunoblotting techniques so that the various
      individual members of the family can be distinguished. This paper describes
      improvements in the immunoblotting technique to distinguish members of the rat
      cytochrome P450 4A subfamily, 4A1, 4A2, and 4A3, as they are present in Sprague
      Dawley rat liver microsomes. This procedure was used to investigate differences
      in the cytochrome P450 4A forms observed under various conditions such as:
      untreated versus peroxisome proliferator treated rats, Sprague-Dawley versus
      Fischer 344 male versus female rats, and liver versus kidney microsomes. In liver
      microsomes of male Sprague-Dawley rats, forms 4A1, 4A2, and 4A3 were induced by
      the peroxisome proliferators, clofibrate, di-(2-ethylhexyl) phthalate,
      dehydroepiandrosterone, aspirin, and ibuprofen. Expression of the 4A forms shows
      strain specificity. A comparison of the cytochrome P450 4A forms in male Sprague
      Dawley and Fischer 344 rats treated with peroxisome proliferators demonstrated
      that three distinct protein bands are visible on immunoblots of liver microsomes
      of Sprague-Dawley rats, whereas only two distinct protein bands are detectable in
      liver microsomes of Fischer 344 rats. The two protein bands in liver microsomes
      of male Fischer 344 rats migrate in positions corresponding to the 4A2 and 4A3
      bands in male Sprague-Dawley rats. There did not appear to be a protein band
      corresponding to the 4A1 band of Sprague-Dawley rats. Expression of the 4A forms
      also shows gender specificity. In liver microsomes of female Sprague-Dawley rats,
      expression of the P450 4A2 form was not observed after treatment with a
      peroxisome proliferator. Expression of the 4A forms also shows tissue
      specificity. In kidney, 4A2 is the major protein band in male Sprague-Dawley rats
      with minor amounts of the 4A3 protein, whereas two prominent protein bands (4A2
      and 4A3) are seen in male Fischer 344 rats.

PMID- 9280411
TI  - Epoxide hydrolase-dependent metabolism of butadiene monoxide to 3-butene-1,2-diol
      in mouse, rat, and human liver.
AB  - Incubations of butadiene monoxide (BMO) with mouse, rat, and human liver
      microsomes or cDNA-expressed human microsomal epoxide hydrolase led to 3-buten
      1,2-diol (BDD) detection; the BDD peak exhibited a GC/MS fragmentation pattern
      similar to that of reference material. Incubations with rat liver cytosol did not
      lead to BDD detection; however, when mouse or human liver cytosol was used, BDD
      was detected but at levels lower than those detected with the liver microsomes.
      The catalytic efficiency (V(max)/K(m) ratio) of BDD formation in rat liver
      microsomes was nearly 3-fold higher than the ratio obtained with mouse liver
      microsomes. Among two human liver microsomal samples, one sample exhibited a
      ratio that was nearly 3-fold higher than that of rat liver microsomes, and the
      second sample exhibited a ratio that was similar to that of rat liver microsomes.
      Although these results suggest epoxide hydrolases may play a role in BMO
      metabolism in vivo, rats and mice given BMO (71.3-285 micromol/kg) excreted <1%
      of the dose as BDD into urine within 24 hr. Thus, further studies into the role
      of epoxide hydrolases in BMO metabolism and disposition and the fate of BDD are
      warranted.

PMID- 9280412
TI  - [Reconstruction of various nasal areas, here: reconstruction of the columella].

PMID- 9280413
TI  - [Early and long-term results of rehabilitation of cochlear implant patients]].
AB  - BACKGROUND: Cochlear implantation is nowadays a reliable and well-accepted method
      of auditory rehabilitation in selected adults and children. METHODS: We present
      rehabilitation data on 21 adult patients provided with the Nucleus CI22 M
      cochlear implant using the SPEAK strategy. RESULTS: Results of first tune-up show
      an open set speech understanding in approximately 50% of patients. Long-term
      results also reveal further improvement in patients who had no open set speech
      understanding. Our data seem to indicate similar results in comparison to other
      groups using the CIS strategy. CONCLUSIONS: In adults, open set speech
      understanding can be achieved even at the first tune-up. Results of early
      rehabilitation seem to be influenced by duration and etiology of deafness,
      experience with hearing aids, and other factors.

PMID- 9280414
TI  - [Contralateral modification of transitory evoked otoacoustic emissions].
AB  - BACKGROUND: In recent publications the influence of contralateral white noise on
      transient evoked otoacoustic emissions (TEOAE) is discussed with regard on
      contributions of the efferent auditory system. METHODS: In the present study the
      effects have been investigated with regards to middle-ear muscles, efferents and
      cross hearing. TEOAE to monaural 40-80 dB SPL clicks were recorded in normal
      hearing adults under simultaneous presentation of 20-60 dB SPL broadband noise to
      the contralateral ear. Control runs were performed before, during a short break
      of, and after contralateral stimulation. The control run before contralateral
      stimulation was used as a reference. RESULTS: Decrease in TEOAE, and increase in
      accompanying noise floor, were found to follow the contralateral stimulation. In
      particular a 1-3 dB decrease was found for contralateral noise levels of 40 and
      60 dB SPL, even though the readings at 60 dB only were statistically significant
      (paired-samples t test, p = 0.05). For both TEOAE and noise floor no systematic
      dependence on click intensity was seen. The control runs during temporary break
      and after contralateral noise revealed an increase in both TEOAE and noise floor.
      As a rule, the TEOAE adapted to the reference within 2-3 min following the
      cessation of contralateral stimulation, whereas the increased noise floor level
      was still noted after 10 min. CONCLUSIONS: Traditionally, suppressing effects of
      contralateral stimulation on TEOAE have been attributed to cochlear efferents
      (CEs). Occasionally, the middle-ear muscle and cross hearing involvement have
      been considered as well. Substantially, the present results and findings of other
      workers are inconsistent with the basic knowledge of CE functioning: (I) The
      decrease in TEOAE under contralateral stimulation is in conflict with an increase
      in cochlear microphonics and summating potentials observed during activation of
      CEs: (II) contralateral suppression of TEOAE exhibited no significant dependence
      on the test-stimulus level while the CEs are known to be efficient in the range
      of the low signal intensities only, and (III) acoustic activation of the CEs can
      hardly be expected to reach levels sufficient to influence the TEOAE mechanism.
      The present findings, i.e. decrease in TEOAE and increase in noise floor level,
      can more reasonably be explained as being mainly attributable to activation of
      the middle-ear muscles.

PMID- 9280415
TI  - [Treatment of cavernous hemangiomas with the neodymium:YAG laser].
AB  - BACKGROUND: Cavernous hemangiomas are benign vascular lesions which are apparent
      at birth or soon thereafter. Although hemangiomas involute spontaneously,
      cosmetically unacceptable results or life-threatening complications may occur,
      necessitating early therapy. METHODS AND PATIENTS: Thirty-four patients with
      facial cavernous hemangiomas were treated with a cw-neodymium:YAG laser. Before,
      during, and after the treatment the skin was cooled with ice. The quartz fiber
      was used in contact or non-contact technique, and in very large hemangiomas we
      used interstitial treatment. RESULTS: In all patients a clear reduction of the
      tumor size was achieved. In 26 cases the tumor disappeared completely. Usually
      there is considerably swelling of the tumor immediately after treatment which
      decreases within some days. Side effects include local hyperemia and slight
      burns. Scarring was seen in only two cases. CONCLUSIONS: Facial cavernous
      hemangiomas can be treated satisfactory by the neodymium:YAG laser. Safe, active
      intervention with this laser is possible in most, if not in all, cases and it
      provides an alternative to other treatment modalities including the neglect of
      these lesions.

PMID- 9280416
TI  - [Mucous membrane melanomas of the upper aerodigestive tract. An analysis of 34
      cases].
AB  - BACKGROUND: Malignant mucosal melanoma of the upper aerodigestive tract is a rare
      disease. The prognosis is expected to be significantly worse than the prognosis
      of cutaneous melanoma and so far no uniform therapeutic concept exists.
      Publications about mucosal melanoma are scarce and reported patient groups are
      usually small. PATIENTS: Thirty-four patients have been registered at the ENT
      Department of the University of Kiel Medical Center with the diagnosis mentioned
      above. Clinical data were obtained from the patient's charts, the minimum follow
      up was three years. RESULTS: Most common site of the tumor was the nasal cavity
      and paranasal sinuses with 28 of 34 patients. Less frequently affected was the
      nasopharynx (three cases), oropharynx, larynx, and middle ear (one case each).
      All patients were caucasians and most of them were of an advanced age (66.9 years
      +/- 12.3). Treatment of choice was surgical resection in 27 cases, in four cases
      it was combined with radiation therapy, in one case with radiation therapy and
      chemotherapy, and in three cases with chemotherapy. Six patients received solely
      radiation therapy, one patient was only treated by chemotherapy. Patients who
      were treated by a combined approach had a more favourable outcome than patients
      who were treated by a monotherapy of surgery, radiation therapy, or chemotherapy.
      A high number of recurrences were observed, which occurred on an average of 16.6
      months after the diagnosis of the primary tumor. Overall 5-year survival was
      45.8%, the 10-year survival rate was 22.3%. CONCLUSIONS: Optimized combined
      therapeutical approaches might possibly improve the prognosis of mucosal melanoma
      of the upper aerodigestive tract. Intervals between follow-ups should be short to
      render detection of relapses at an early stage. Repeated therapy of recurrent
      disease might lengthen survival.

PMID- 9280417
TI  - [Detection of differentially expressed genes in head-neck carcinomas].
AB  - BACKGROUND: Carcinogenesis is generally considered a multistage process based on
      many alterations of the genetic substance. These alterations lead to many
      qualitative and quantitative changes in gene expression with subsequent malignant
      transformation of the cell. Only a few of these genetic alterations are
      identified yet. METHODS: The differential display reverse transcriptase
      polymerase chain reaction was employed to detect differentially expressed genes
      in head and neck cancer. The mRNA expression of cultivated keratinocytes of the
      upper aerodigestive tract was compared to the one of cultivated squamous cell
      carcinoma cells of the larynx, hypopharynx, and floor of the mouth. RESULTS: A
      total of 116 differentially expressed gene fragments were identified. They were
      either solely expressed by the malignant cells or the keratinocytes or in just
      one carcinoma cell entity. Forty-three of the 116 DNA fragments were sequenced
      successfully. In four cases the specific differential expression was confirmed by
      Northern blot hybridisation in comparison to keratinocytes, normal mucosa, and 3
      benign tumors from the head and neck region. A gene bank search revealed in three
      cases a homology of less than 20% to already known human, animal, bacterial or
      viral gene sequences and in one case a homology of 98% with a human gene
      sequence. CONCLUSIONS: The detected for squamous cell carcinoma of the head and
      neck specific genes or gene fragments are the basis for further investigations to
      better understand carcinogenesis.

PMID- 9280418
TI  - [Tuberculosis of the parotid gland: a rare differential diagnosis of parotid
      tumor].
AB  - BACKGROUND: Mycobacterial infection of the parotid gland is rare even in
      countries where the disease is rife. Because patients do not have specific
      symptoms of tuberculosis and tuberculosis of the parotid gland frequently
      presents as a neoplasm, most patients undergo parotidectomy. PATIENTS: In this
      text we present a case report and the review of 20 well documented cases from the
      literature. The problems of diagnosis and therapy, especially the problem of
      distinguishing tuberculous infection from another parotid swelling such as a
      benignoma or a granuloma, are analyzed. RESULTS: Eighty percent of the patients
      we reviewed in our investigation originated from Asian or African countries. In
      most cases the history of the parotid swelling was shorter than one year, often
      even shorter than six months. In 17 of the 20 patients tuberculosis presented as
      a solid mass corresponding to the infection of a parotid lymph node. In three
      cases a diffuse infection of the whole gland was described. It was frequently
      impossible to distinguish tuberculosis from swelling of the parotid gland due to
      other causes by clinical or sonographical investigations. History of tuberculosis
      was given in two cases: the patients underwent an antituberculous therapy one and
      five years ago. The chest radiograph was normal in all but one cases. In two
      cases pretherapeutic diagnosis was made by biopsy, in two cases by fine needle
      aspiration cytology, which was performed in a total of seven cases. CONCLUSION:
      Tuberculosis is a rare cause for parotid swelling. Nationality of the patient and
      a short history of the swelling may suggest a mycobacterial infection. Diagnosis
      by fine needle aspiration cytology may be difficult. Other investigations should
      be added, if necessary. Antituberculous therapy has to be done also in cases of
      organ tuberculosis after surgery. If the right diagnosis is known before therapy,
      parotictomy can be avoided.

PMID- 9280419
TI  - [A case of sarcoidosis of the mastoid].
AB  - BACKGROUND: Sarcoidosis is a common granulomatous systemic inflammatory disease
      mainly affecting the interstitial lung tissue and perihilar lymph nodes. Since
      its first description by Bernier 1889 its etiology has remained obscure. METHOD:
      Sarcoidosis of the right middle ear in a 38-year-old woman was diagnosed by
      biopsy. RESULT: After mastoidectomy and treatment with prednisolone the patient
      has been free of relapse for two years. CONCLUSION: According to our knowledge
      this is the second reported case of sarcoidosis of the middle ear. In both cases
      the interstitial lung tissue has been involved as well. This finding increases
      the importance of excluding sarcoidosis in differential diagnosis of chronic
      otitis media.

PMID- 9280420
TI  - [Sarcoidosis of the paranasal sinuses as the etiology of therapy refractory
      dacryocystitis].
AB  - BACKGROUND: Sarcoidosis is a chronic systemic disease of unknown etiology
      characterized by non-caseating granulomatous inflammation of various organs. The
      clinical findings when nasal mucosa is involved include nasal crusting,
      epistaxis, pain and/or anosmia, nasal polyps, or submucosal nodularity. CASE
      REPORT: We describe a case of sarcoidosis of the paranasal sinuses. In a 33-year
      old man, the first symptom was therapy resistant putrid dacryocystitis. Further
      there had been symptoms of chronic sinusitis. A CT scan revealed swelling of the
      mucosa in the anterior ethmoid, frontal recess, and maxillary sinus. As the
      disease obviously affected the region of the nasolacrimal duct with consecutive
      stenosis of this canal, we opted for endoscopic sinus surgery. A few days after
      this endoscopic procedure, the dacryocystitis had healed. RESULTS: The
      histopathological examination showed the typical picture of sarcoidosis that had
      its primary manifestation in the paranasal sinuses. According to these findings
      further explanation of the patient was necessary. The diagnosis of sarcoidosis
      was confirmed by lavage and biopsy material of bronchoscopically suspect lung
      areas. Consequently, the patient underwent a long-term corticoid therapy and
      today, 10 months after the surgical intervention, the patient is free of
      symptoms. Follow-up endoscopy of the paranasal sinuses showed no further
      pathological findings. CONCLUSION: Our case demonstrates that the first
      manifestation of sarcoidosis can be in the paranasal sinuses.

PMID- 9280421
TI  - [History of the tuning fork. II: Evolution of the classical experiments by Weber,
      Rinne and Schwabach].
AB  - BACKGROUND: Since the 17th centrury it was known that sounds could be perceived
      via air conduction and bone conduction and that this provided a means of
      differentiating between hearing disorders located in the middle ear and those
      located in the acoustic nerve. For a long time to come, however, there was no
      need for such a differential diagnosis. After the invention of the tuning fork in
      1711 this instrument had soon become widely used in music, but it took well over
      100 years until it was introduced into physiology and otology. FROM DIRECTIONAL
      HEARING TO WEBER'S TEST: J. B. Venturi, a physicist in Modena, Italy, in 1802 had
      shown that the perception of the direction from which a sound is coming is
      governed by the fact that one ear is hit by the sound more intensely than the
      other ear. C. T. Tourtual, a physician in Munster, Germany, demonstrated in 1827
      that this also holds true for sound conducted via the skull bones. He used a
      watch as sound source. He found that occlusion of both ear canals would increase
      the sensation in both ears equally, but that occlusion of only one ear would
      increase the sensation only in the occluded ear, thus giving the impression that
      the sound were coming from that side. He was interested in a comparison between
      vision and audition, and he concluded that with regard to recognizing the
      direction of a sensory signal vision was superior to audition. In the same year
      1827 C. Wheatstone, a physicist in London, investigating the mode of vibration of
      the tympanic membrane and using a tuning fork found the same phenomena as
      Tourtual and some more effects. E. H. Weber, an anatomist and physiologist in
      Leipzig, Germany, described the very same phenomena as Tourtual and Wheatstone
      once more in 1834. He wanted to prove that airborne sound is perceived by the
      vestibulum and the semicircular canals, bone conducted sound by the cochlea. None
      of these investigators was thinking of a clinical use of their findings and made
      no such suggestion. E. Schmalz, an otologist in Dresden, Germany, in 1845
      introduced the tuning fork and the test later named after Weber into otology and
      explained in great detail all possibilities of a diagnostic evaluation of the
      test. His grand achievement, however, passed unnoticed at his time. THE RINNE
      TEST: A. Rinne, a physician in Gottingen, Germany. In 1855 described the test
      which later was named after him, in an elaborate treatise on the physiology of
      the ear. He wanted to demonstrate that in man and animals living in the air, as
      opposed to those living in water, the conduction of sound via the bones of the
      skull is just an unavoidable side effect of sound perception. He mentioned a
      clinical application of his test only in a footnote and obviously never used it
      himself in a systematic way. His test was made generally known by Lucae in Berlin
      only after 1880. The value of Weber's and Rinne's tuning fork tests was much
      disputed even at the turn of the century and only gradually became generally
      accepted.

PMID- 9280423
TI  - [Interesting case no. 2. Right glomus caroticum tumor].

PMID- 9280422
TI  - [Voice disorders. Emphasis in diagnosis and therapy].
AB  - The knowledge required in this field exceeds by far the area of traditional
      laryngology. The paper provides an overview of some basic measures, concentrating
      on functional aspects that are considered indispensible for the competence of the
      ENT doctor prescribing voice therapy to be carried out by non-medical therapists.

PMID- 9280424
TI  - [Meningococcal meningitis].

PMID- 9280425
TI  - [Nerve enlargement in a girl with Charcot-Marie-Tooth disease type 1A].

PMID- 9280426
TI  - [Primary cerebral tumors: the reality and the molecular basis of future
      treatment].

PMID- 9280427
TI  - [Isolated vasculitis of the peripheral nervous system].
AB  - We present a patient with a subacute asymmetrical sensorimotor polyneuropathy.
      The pathological features were predominantly loss of nerve fibers, axonal
      degeneration and healed vasculitis. The epineural vessels were involved, while
      endoneurial capillaires were preserved. Muscle biopsy revealed neurogenic
      features with normal blood vessels. After three years, motor and sensory function
      was almost normal, without any specific treatment. No abnormal findings
      suggesting collagen diseases or other underlying immunological disorders were
      obtained by various laboratory tests. In conclusion, the present case strongly
      suggests that the vasculitis was confined to the peripheral nerves.

PMID- 9280428
TI  - [Methotrexate in the treatment of inflammatory intestinal diseases].

PMID- 9280429
TI  - [Familial visceral myopathy].
AB  - We report a patient with intestinal pseudo-obstruction in which both the
      histopathological findings and the clinical history strongly suggest a visceral
      myopathy of familial type. Reviewing the clinicopathological descriptions of the
      different families appearing in the literature, is evident that both the
      presentation (severity, distribution of lesions, etc) and the inheritance pattern
      seem not to be clearly delimitated, and it has been recently suggested that it
      may be related to the mitochondrial myopathies. The useless of conventional
      biopsy procedures (due to the almost exclusive affectation of the external muscle
      layer of the intestinal wall); the frequently patchy distribution of the lesions
      (which might be overlooked in a routine histological handling of a resection
      specimen) and the extensive range of symptoms of the disease, support the
      paramount importance of a high index of suspicion (obviously, the clinical
      history plays a fundamental role). In this setting, it is also interesting to
      emphasize the utility of manometric studies for the correct diagnosis and
      management of these patients; as well their possible application to identify
      asymptomatic heterozygotes.

PMID- 9280430
TI  - [Treatment with recombinant interferon alfa-2b of a patient with chronic
      hepatitis C and concomitant ulcerative colitis].
AB  - The case of a patient ulcerative colitis involving an autoimmune base who was
      treated with recombinant alpha-2b interferon for presenting chronic active
      hepatitis in relation to virus C is reported. Such treatment was achieved in
      addition to improving the hepatic disease normalizing the transaminases control
      the outbreak of ulcerative colitis that the patient was presenting from some days
      before beginning the treatment. Various aspects are discussed related to the
      autoimmunity in the ulcerative colitis and in the chronic C hepatitis and the
      exarcebation of autoimmune phenomena which may lead to interferon therapeutic. As
      a basis for the above and the review of the literature, we concluded that the
      existence of ulcerative colitis does not contraindicate the use of alpha-2b
      interferon in patient with chronic hepatitis, although special control of the
      disease should be carried out during the treatment period.

PMID- 9280431
TI  - [Anisakidosis of the colon as a cause of acute abdomen].
AB  - We report a case of acute abdomen caused by the invasion of the ascending colon
      by larvae of Anisakis simplex in a 57 year-old-woman whose initial symptoms were
      colic abdominal pain, diarrhea and fever. The diagnosis was done by the
      histological study of the surgical specimen in which two parasites were
      morphologically identified in the submucosa. Although a causal relationship of
      the disease with the ingestion of crude fish could not be established initially,
      there were antecedents of ingestion of anchovy in vinegar (Engraulis
      encrasicholus) and dyspeptic symptoms for several months.

PMID- 9280432
TI  - [Leiomyosarcoma of the inferior vena cava: therapeutic and clinical
      considerations].
AB  - We report a case of leiomyosarcoma of the lower segment of the inferior vena cava
      in a fifty nine year old man who presented with bilateral leg edema on physical
      exploration. Ultrasonography, computed tomography scan and intravenous urography
      demonstrated the existence of a retroperitoneal tumour. The tumour and the
      affected venous fragment were resected. Postoperative radiotherapy was given. The
      patient was re-operated on three years later because of extra-local recurrence.
      Two years later the patient is assymptomatic and without radiological evidence of
      recurrence and/ or metastasis.

PMID- 9280433
TI  - [Obstructive jaundice from an adenomyoma of the ampulla of Vater].

PMID- 9280434
TI  - [Intrafamilial transmission of the hepatitis C virus].

PMID- 9280436
TI  - [Intrahepatic lithiasis].

PMID- 9280437
TI  - Changes in the regiospecificity of aromatic hydroxylation produced by active site
      engineering in the diiron enzyme toluene 4-monooxygenase.
AB  - Pseudomonas mendocina KR1 toluene 4-monooxygenase is a multicomponent diiron
      enzyme. the diiron center is contained in the tmoA polypeptide of teh hydroxylase
      component [alphabetagamma)2,Mr approximately 212 kDa]. Product distribution
      studies reveal that the natural isoform is highly specific for para hydroxylation
      of toluene (kcat approximately 2 s-1 with respect to an alphabetagamma promoter),
      o-xylene (kcat approximately 0.8 s-1), m-xylene (kcat approximately 0.6 s-1), and
      other aromatic hydrocarbons. This degree of regioselectivity for methylbenzenes
      is unmatched by numerous other oxygenase enzymes. However, during the T4MO
      catalyzed oxidation of p-xylene (kcat approximately 0.4 s-1), 4-methyl benzyl
      alcohol is the major product, showing that the enzyme could catalyze either
      aromatic or benzylic hydroxylation with the appropriate substrate. Site-directed
      mutagenesis has been used to study the contributions of tmoA active site residues
      Q141, I180, and F205 to the regiospecificity. Isoforms Q141C and F205I yielded
      shifts of regiospecificity away from p-cresol formation, with F205I giving an
      approximately 5-fold increase in the percentage of m-cresol formation relative to
      that of the natural isoform. The kcat of purified Q141C for toluene oxidation was
      approximately 0.2 s-1. Isoform Q141C also functioned predominantly as an aromatic
      ring hydroxylase during the oxidation of p-xylene, in direct contrast to the
      predominant benzylic hydroxylation observed for the natural isoform, while
      isoform F205I gave nearly equivalent amounts of benzylic and phenolic products
      from p-xylene oxidation. Isoform I180F gave no substantial shift in product
      distributions relativeto the natural isoform for all substrates tested. Upon the
      basis of a proposed active site model, both Q141 anf F205 are suggested to lie in
      a hydrophobic region closer to the FeA iron site, while I180 will be closer to
      FeB. These studies reveal that changes in the hydrophobic region predicted to be
      nearest to FeA can influence the regiospecificity observed for toluene 4
      monooxygenase.

PMID- 9280435
TI  - [Gastric emptying in patients with morbid obesity treated with a duodenal
      switch].

PMID- 9280438
TI  - Structures of active conformations of UMP kinase from Dictyostelium discoideum
      suggest phosphoryl transfer is associative.
AB  - UMP/CMP kinase from Dictyostelium discoideum (UmpKdicty) catalyzes the specific
      transfer of the terminal phosphate of ATP to UMP or CMP. Crystal structures of
      UmpKdicty with substrates and the transition state analogs AlF3 or BeF2 that lock
      UmpKdicty in active conformations were solved. The positions of the catalytic
      Mg2+ and the highly conserved lysine of the P loop are virtually invariant in the
      different structures. In contrast, catalytic arginines move to stabilize charges
      that develop during this reaction. The location of the arginines indicates
      formation of negative charges during the reaction at the transferred phosphoryl
      group, but not at the phosphate bridging oxygen atoms. This is consistent with an
      associative phosphoryl transfer mechanism but not with a dissociative one.

PMID- 9280439
TI  - Orientation of the phylloquinone electron acceptor anion radical in photosystem
      I.
AB  - The photosynthetic reaction center of photosystem I (PS I) contains a
      phylloquinone molecule (A1) which acts as a transient electron acceptor. In PS I
      form the cyanobacterium Synechocystis PCC 6803 under reducing conditions, we have
      photoaccumulated an EPR signal assigned to the phylloquinone radical anion. The
      phylloquinone EPR spectrum has been studied in oriented multilayers of PS I using
      EPR at 9 GHz. In addition, the phyllosemiquinone spectrum has been obtained at
      283 GHz using high-field, high-frequency EPR spectroscopy. From the orientation
      dependence of the spectrum at 9 GHz and the resolved g values obtained at 283
      GHz, the phyllosemiquinone ring plane was determined to be almost perpendicular
      to the membrane (76 degrees) while the oxygen-oxygen (O-O) axis of the quinone
      was found to make an approximate 63 degrees angle to the membrane plane. The
      orientation of the ring plane is similar to that determined for the quinone
      electron acceptor (QA) in the purple bacterial reaction center, while the
      orientation of the O-O axis is significantly different. The new orientation
      information, when taken with data in the literature, allows the position of the
      phylloquinone in the reaction center to be better defined.

PMID- 9280440
TI  - [Present and future of specialized training in family medicine].

PMID- 9280441
TI  - [Grief for loss of a spouse: a study with discussion groups in primary care].
AB  - OBJECTIVE: To understand the grieving process after the loss of a spouse and to
      find the opinion of the person grieving about the best intervention under the
      circumstances. DESIGN: Qualitative, with discussion groups. SETTING: Primary
      care. PATIENTS AND OTHER PARTICIPANTS: Widowers/widows between 30 and 70, who
      suffered their loss between 3 months and 2 years before the study. MEASUREMENTS
      AND MAIN RESULTS. The data were obtained from recordings and transcriptions, and
      the main ideas analysed. Two groups were defined: 11 widows between 49 and 68
      years old and 6 widowers between 36 and 70. The majority of deaths had followed a
      previous terminal illness. Four phases of grief were found: 1) anticipated grief,
      2) early grief, 3) intermediate grief and 4) delayed grief. There were
      differences between widows and widowers. An intervention could involve: pre
      arranged appointments, home visits, and groups and, in general, spaces to be able
      to "talk". CONCLUSIONS: The results, in so far as they refer to the grieving
      process and similarities and differences of type, coincide with other authors.
      The participants highlighted the importance of psychological support from health
      workers during the last moments of the illness and the importance of this in how
      grieving developed. Similarly, they evaluated their own support to the dying
      spouse as an additional factor which helped them.

PMID- 9280442
TI  - [Reliability of 3 sources of information about medication excipients].
AB  - OBJECTIVE: To find how reliably three sources of therapeutic information record
      the composition of excipients: the Vademecum, the pharmaceutical catalogue and
      the instructions sheets of pharmaceutical products. DESIGN: Descriptive study.
      SETTING: Primary care. PATIENTS AND OTHER PARTICIPANTS: Initially, 658 orally
      taken products were selected. Whether four excipients (saccharine, saccharose,
      lactose and ethanol) appeared in these products' composition formulas was
      compared. RESULTS: In 70.6% +/- 5.11 there was discordance on the excipients in
      the composition formulas in one of the three sources of therapeutic information.
      The instructions sheets contained information on the number of excipients in
      98.7% +/- 1.3 of the products, the pharmaceutical catalogue in 87.2% +/- 3.7 and
      the Vademecum in 65.7% +/- 5.3. So the Vademecum was the source of therapeutic
      information containing the highest percentage of products with no kind of
      information about excipients, followed by the catalogue and the instructions
      sheets. The instructions sheets were the best source of therapeutic information
      for 289 products. 10.3% of laboratories did not quantify their excipients in any
      of the three sources under study. CONCLUSIONS: The Vademecum and pharmaceutical
      catalogue do not include very reliable information about these four excipients in
      the composition formulas of pharmaceutical products. It is important to make
      available to doctors straightforward texts which provide more reliable and up-to
      date information.

PMID- 9280444
TI  - [Evaluation of a community experience of social interaction and promotion of
      exercise and leisure time: subjective impact and participant's satisfaction].
AB  - OBJECTIVE: To evaluate an experiment in social interaction, physical exercise and
      use of leisure time of 50 to 75-year old women using a health centre. DESIGN: An
      observational and descriptive study of a qualitative nature. SETTING: A Health
      District in the city of Jaen. PARTICIPANTS: 40 women between 50 and 75 chosen by
      their G.P. because they suffered conditions which could be improved by physical
      exercise, had adverse social conditioning factors and/or non-specific symptoms
      which were probably psychosomatic. INTERVENTION: The programme developed between
      October '94 and June '95 included three activities. Two groups of 20 women were
      formed. 100% completed the programme. MEASUREMENTS AND MAIN RESULTS: 94% of the
      participants thought that their health had improved; 89%, their family life; and
      97%, their social and personal life. On completing the programme, 71% considered
      their health "good or very good". 83% attended the physical exercise sessions
      with less than three absences; all of them stayed on for the 95-96 course. Their
      reasons for beginning the course corresponded fully with the benefits perceived
      on completing it. CONCLUSIONS: In line with the opinions of the participants in a
      programme of intersector activity (community social services and the health
      service), group physical exercise, with socializing and amusement components, has
      positive effects on health and social and family well-being.

PMID- 9280443
TI  - [Comparative study of normal and over-users of a health center].
AB  - OBJECTIVE: To compare normal users (NU) and over-users (OU), examining social and
      demographic features, family characteristics, presence of psychological problems
      or family dysfunction and the existence of chronic pathologies. DESIGN: An
      observational crossover study, lasting one year (1994). SETTING: Health centre.
      PATIENTS AND OTHER PARTICIPANTS: Randomised sampling of 12,092 patients > 14
      years old. OU (n = 260) was defined as someone who had a percentage point for
      attendance without an appointment at the Centre, excluding bureaucratic reasons,
      of above 75%; and NU (n = 260), in the 25 and 75% band. 65 individuals (240 OU
      and 225 NU) took part. MEASUREMENTS AND MAIN RESULTS: Average age of OU was
      higher than that of NU. 88 OU (36.7%) finished their education above primary
      level, whereas 115 NU (51.1%) did so (OR 1.81). 37.5% OU (90) belonged to small
      families, against 24.9% NU (56). 34.6% OU (83) were in an advanced family vital
      cycle, against 24% NU (54. 26.7% OU (64) and 17.8% NU (40) had psychological
      problems. There was family dysfunction in 32 OU (13.3%) and 23% NU (10.2%). 186
      OU (77.5%) had some chronic pathology, against 96 NU, of whom 70.3% OU and 87.2%
      NU attended appointments arranged to monitor these pathologies. CONCLUSIONS: Over
      use of our health centre is related to being older, a low level of education,
      belonging to small families in an advanced vital cycle, having psychological
      problems, suffering chronic pathologies and not attending appointments when they
      are arranged.

PMID- 9280445
TI  - [Use of inhaled bronchodilators by primary care patients].
AB  - OBJECTIVE: To find how widespread incorrect inhalation techniques are in patients
      on long-term inhalation treatments, comparing different methods and the health
      control standard. DESIGN: A descriptive crossover study. SETTING: Three Health
      Centres in Burgos. PATIENTS: People over 15 with at least a month on inhalation
      treatment. MEASUREMENTS AND MAIN RESULTS: A questionnaire was composed to find
      the characteristics of the patients and their illness. Then their inhalation
      method was qualified as correct, acceptable or incorrect, using a scale based on
      Newman's classic criteria. Average age was 63.8 +/- 15.6, with 66.5% men. 11.6%
      of patients were active smokers. The most common diagnosis was COPD (61.6%). 65%
      of the patients were monitored within primary care (PC). The most common
      inhalation method was pressurised aerosol (61%); 26.2% of patients used two or
      more different methods. Only 21.3% of patients correctly performed the technique
      of inhalation, with better results for patients under specialist care (SC) than
      PC. 10.5% of patients had never received instruction on an inhalation technique.
      The method with the best results was the dry dust one, with differences close to
      statistical significance. CONCLUSIONS: There is widespread incorrect use of
      methods of inhalation. Most people use a pressurised aerosol. There are a large
      number of patients who have never been shown the correct way to inhale.

PMID- 9280446
TI  - [Mental health in primary care: a bibliometric study].
AB  - OBJECTIVE: The quantification and analysis of the studies published in the
      journal Atencion Primaria on mental health since it first came out up to the
      present. DESIGN: A descriptive study based on the review of the journal's tables
      of contents. SETTING: All the studies published in the journal between 1984 and
      1995. MAIN RESULTS: A total of 151 studies on themes connected with mental health
      have been published since the journal first came out. Most belonged to the
      sections "Original articles" (57), "Short reports" (17) and "Letters to the
      editor" (39). Many of the studies concerned disorders arising from substance
      abuse (76, of which 32 deal with alcohol and 37 tobacco dependency). Only 31
      studies dealing with other mental disorders were found. Among these, disorders as
      important as affective and demential disorders only had three articles each. The
      proportion of studies was similar in different years. CONCLUSIONS: Despite the
      importance of mental disorders in primary health care, very few studies on this
      question have appeared in the journal Atencion Primaria, and even fewer if
      anecdotical and administrative articles are excluded. It is to be hoped that, in
      the future, interest in mental health and the publication of articles on this
      question will increase.

PMID- 9280447
TI  - [Non-steroid anti-inflammatory agents and gastrointestinal protection: adequate
      prescription in primary care?].
AB  - OBJECTIVES: To find the frequency of prescription of gastro-intestinal protectors
      (GIP) at the same time as non-steroidal anti-inflammatory drugs (NSAID). To find
      certain characteristics linked to their use in primary care. To evaluate how
      correctly they are prescribed. DESIGN: A crossover descriptive study. SETTING: A
      base urban health area. PATIENTS: Patients over 14, who attended in 1994, who had
      a medical history and were treated with NSAID. MEASUREMENTS AND INTERVENTIONS:
      1,115 medical histories were obtained by simple randomised sampling, of whom 205
      were under treatment with NSAID. A questionnaire was used to evaluate: age, sex,
      NSAID treatment, GIP, history of peptic ulcer, corticoid or acenocoumarol
      treatment, tobacco, alcohol and related pathology. After a complete bibliographic
      review, some criteria were fixed for when it is correct to give GIP-NSAID.
      RESULTS: The prevalence of NSAID prescription was 18.39%. 34 patients treated
      with NSAID received GIP at the same time. Aceclophenac was the most widely
      prescribed NSAID; and H2 antihistamines, the drugs most commonly used as GIP.

PMID- 9280448
TI  - [Outbreak of an epidemic of conversion disorder].

PMID- 9280449
TI  - [The necessary elimination of well-being status from going from public health to
      beneficence].

PMID- 9280450
TI  - [Practical considerations in the treatment of patients with AIDS and
      tuberculosis].

PMID- 9280451
TI  - [Evaluation of the Accutrend GC for cholesterol determination].

PMID- 9280452
TI  - [Notification of cancer diagnosis].

PMID- 9280453
TI  - [Patho- and morphogenesis of alcoholism].

PMID- 9280454
TI  - [The effect of adrenaline and 17beta-estradiol sulfate on transmembrane
      potentials of guinea pig cardiomyocytes].

PMID- 9280455
TI  - [The effect of liposomal form of L-Dopa on the level of dopamine, its
      metabolites, and phospholipid metabolism in the striatum of mice with
      experimental parkinsonian syndrome].

PMID- 9280456
TI  - [Potentiating and delaying effect of dalargin analogs on the duration of
      experimental nembutal-induced sleep].

PMID- 9280457
TI  - [Adaptation to physical exertion increases activity of prostaglandins E and I2
      and reduces the stress-reaction].

PMID- 9280458
TI  - [Evaluation of the level of lipid peroxidation during acute poisoning with
      organophosphorus pesticide in cats and the effect of antioxidants on their
      survival].

PMID- 9280459
TI  - [Characteristics of specific binding sites for high density lipoproteins on the
      surface of rat hepatocytes; the effect of estradiol and testosterone].

PMID- 9280460
TI  - [Binding ability of rat serum albumin during tetrachloromethane intoxication and
      administration of anti-oxidants, anti-hypoia agents, and actoprotectors].

PMID- 9280461
TI  - [Comparative study of the antioxidant properties of pharmacological agents
      blocking histamine receptors in an in vitro model system].

PMID- 9280462
TI  - [Comparative evaluation of the effect of dimebon, obzidan, finoptin, and
      cordarone on the functional state of the ischemic focus and the size of necrosis
      zone during experimental myocardial infarction].

PMID- 9280463
TI  - [Immunoreactivity of nuclear protein p53 in differentiated thyroid cancers].

PMID- 9280465
TI  - [Factors of resistance of ovarian cancer to combined chemotherapy with the use of
      platinum derivatives].

PMID- 9280464
TI  - [Mechanism of the transport of novel nitrosoalkylurea derivative, nitrulline,
      into tumor and normal cells].

PMID- 9280467
TI  - [The effect of hydrolipophilic balance of muramyl dipeptide derivatives on their
      interaction with biomembranes and incorporation into cells].

PMID- 9280466
TI  - [Metastatic phenotype of a substrain of human melanoma Mel-7 transplanted into
      various immunodeficient mice].

PMID- 9280468
TI  - [Determination of the concentration of the cardioprotective drug cardiochrome in
      the plasma of patients].

PMID- 9280470
TI  - [Prolactin receptors in bile duct cells during rat ontogenesis].

PMID- 9280469
TI  - [Comparative anti-arrhythmia activity of befol, lidocaine, and bonnecor].

PMID- 9280471
TI  - [Development of the chemosensory apparatus of human tongue in postnatal
      ontogenesis].

PMID- 9280472
TI  - [Ultrastructural organization of the hemato-C-cellular interactions in the
      thyroid gland of 4-week-old rats desympathectomized with guanethidine].

PMID- 9280473
TI  - [Ultrastructural and stereological characteristics of epitheliocytes from the
      stomach of wild microtinae rodents during anthropogenic environmental pollution].

PMID- 9280474
TI  - [Structural organization of bone minerals].

PMID- 9280475
TI  - [Changes in the ultrastructure of epitheliocytes of large intestine of
      conventional and gnotobiotic minipigs after exposure to choleragen].

PMID- 9280476
TI  - [The type of changes in the histone/DNA ratio during ontogenesis of multicellular
      organisms].

PMID- 9280477
TI  - [New accents of the classical concept of stress].

PMID- 9280478
TI  - [Melatonin biosynthesis in the epiphysis during early postnatal ontogenesis in
      healthy persons and in patients with hereditary retinal degeneration].

PMID- 9280480
TI  - [Disorders of REM sleep during experimental depressive syndrome induced by
      systemic administration to rats of 1-methyl-4-phenyl-1,2,36-tetrahydropyridine
      (MPTP)].

PMID- 9280479
TI  - [The role of dopaminergic mechanism in the realization of immunostimulating
      effect of substance P and its analog].

PMID- 9280481
TI  - [The role of thrombin in the activation of heparin secretion by mast cells during
      immobilization stress in rats].

PMID- 9280482
TI  - [Permeability of blood-brain barrier in newborn rats during hyperthermia-induced
      seizures].

PMID- 9280483
TI  - [The effect of prolonged parenteral administration of liposomes and L-Dopa
      incorporated into liposomes on metabolism of dopamine and its metabolites in the
      striatum of mice with experimental parkinsonian syndrome].

PMID- 9280484
TI  - [Effect of opiate receptor ligands on the morpho-functional state of the
      sympathico-adrenal system and electrical stability of the heart in acute exposure
      to cold].

PMID- 9280485
TI  - [Reactions of the erythropoietic progenitor cells in various types of neurotic
      actions].

PMID- 9280486
TI  - [Toxic effect of glutamate on cultured cerebellar granular cells reduces the
      intracellular level of ATP. The role of Ca2+ ions].

PMID- 9280487
TI  - [Regulation of 14C-cholesterol capture from mixed micelles in the organ culture
      of epithelial explants of human small intestine mucosa: effects of selective
      inhibitors of ACAT].

PMID- 9280488
TI  - [Changes in the level of met-enkephalin in various brain structures during
      formation of immune response].

PMID- 9280489
TI  - [Effect of amiridine on the state of conditioned reflex in rats with injured
      hippocampus].

PMID- 9280490
TI  - [The role of pathological process in the formation of variability of
      microbiological phenotype in human intestines].

PMID- 9280491
TI  - [Kinetics of hematopoietic clones in reconstituted mice].

PMID- 9280492
TI  - [Isolation and characteristics of recombinant ligand-binding domain of human low
      density lipoprotein receptor].

PMID- 9280494
TI  - [A method of restoration of bile loss during acholia].

PMID- 9280495
TI  - [Comparative study of structural transitions in erythrocyte membranes in donors
      and newborns].

PMID- 9280493
TI  - [Sex steroid-binding globulin, free serum testosterone, and androgen receptors in
      the skin during papulo-pustulosa and conglobate forms of acne vulgaris].

PMID- 9280497
TI  - [Ultrastructural stereological analysis of monkey lungs during experimental Ebola
      fever].

PMID- 9280496
TI  - [Experimental evaluation of the use of recombinant prourokinase and its
      immobilized forms in the treatment of postoperative fibrinoid syndrome in
      ophthalmology].

PMID- 9280498
TI  - [Interaction of erythrocyte and tissue insulin receptors].

PMID- 9280499
TI  - [The effect of mu-opioid receptor agonist tetrapeptide A10 on the DNA synthesis
      in the myocardium and liver of albino rats during early stages of postnatal
      ontogenesis].

PMID- 9280500
TI  - [Cytological analysis of histone component of chromatin from hepatocyte nucleus
      during disorders of vagus innervation of the rat liver].

PMID- 9280501
TI  - [Specific binding of triiodothyronine with nucleoplasma].

PMID- 9280502
TI  - [Ultrastructure of blood and lymphatic capillaries of bronchi during their
      inflammation and endobronchial laser therapy].

PMID- 9280503
TI  - [Morphology of stomach endocrine glands of the porcupine].

PMID- 9280504
TI  - [Pathomorphology of rat lungs during postradiation period].

PMID- 9280505
TI  - [Reaction of popliteal lymph node during its transcutaneous irradiation with
      helium-neon laser].

PMID- 9280506
TI  - [Common clinical manifestations of serotonin deficiency and intoxication
      syndromes].

PMID- 9280507
TI  - [Effect of erythropoietin on protein permeability of rats abdominal aortic wall].

PMID- 9280508
TI  - [Changes of diaphragmatic nerve activity during stimulation of rostral parts of
      ventral surface of rat's medulla oblongata].

PMID- 9280510
TI  - [Effect of donor CSF on restoration of motor function after partial cerebral
      decortication].

PMID- 9280509
TI  - [Effect of estradiol on behavioral reactions of female non-mature rats].

PMID- 9280511
TI  - [Role of mast cells in regulation of erythropoiesis during inflammation].

PMID- 9280513
TI  - [Effect of lidocaine on ultrastructural changes in jejunum, kidney medulla and
      lungs of suckling rabbits, caused by vibrio cholerae].

PMID- 9280512
TI  - [Adaptogen ADAPT modulates synthesis of inducible stress protein HSP 70 and
      increases organism resistance to heat shock].

PMID- 9280514
TI  - [Adrenergic dependence of hematopoietic precursors proliferation under cytostatic
      effect].

PMID- 9280515
TI  - [Antioxidant effect of cytochrome C during prolonged immobilization stress].

PMID- 9280516
TI  - [Adrenal glands catecholamines of August and Wistar rats in acute emotional
      stress].

PMID- 9280517
TI  - [Palmitoylcarnitine-important component of lipid bilayer synaptosome membranes
      reparation system in oxidative stress].

PMID- 9280518
TI  - [Role of intracellular signal systems in regulation of erythrocytes potassium
      channels activated by Ca2+].

PMID- 9280519
TI  - [Central K1-opiate receptors and mechanisms of arrhythmogenesis].

PMID- 9280520
TI  - [Energizing and antihypoxic effects of energostime].

PMID- 9280521
TI  - [Early stages in mechanisms of glucocorticoids action on human thrombocytes:
      effect of hydrocortisone on intracellular cAMP and Ca2+].

PMID- 9280522
TI  - [Comparative characteristic of sodium blocking properties of anti-arrhythmia
      agents on isolated rats cardiomyocytes].

PMID- 9280523
TI  - [Investigation of diabetogenic action of xanthurenic acid].

PMID- 9280524
TI  - [Estimation of fast reversible effects of ethanol and pharmacokinetic prognosis].

PMID- 9280525
TI  - [Effect of hydrocortisone on levels of amines in thymus].

PMID- 9280526
TI  - [Cytokines therapy of purulent wounds in experiment].

PMID- 9280527
TI  - [Activity of benzamide and it's derivatives against botulinum intoxication].

PMID- 9280528
TI  - [Ultraviolet photo-modification of leukocyte's functional state in experimental
      endotoxemia].

PMID- 9280530
TI  - [Effect of combined treatment with hydroxyapatite and estrone on tooth alveolus
      healing in experiment].

PMID- 9280531
TI  - [Role of human fetal tissue transplantation in rheumatoid arthritis].

PMID- 9280529
TI  - [Calmodulin in osteogenic sarcoma].

PMID- 9280532
TI  - [Metabolism of sialic compounds in pathogenesis of chronic osteomyelitis].

PMID- 9280534
TI  - [Specific binding of 3n-melatonin with plasma cell membrane in rats thyroid
      gland].

PMID- 9280533
TI  - [Age-related vagal regulation features of chronotropic heart function in
      sympathectomized and intact rats].

PMID- 9280535
TI  - [Ontogenetic dynamics of blood pressure and characteristics of EKG in rats of
      NISAG line with congenital arterial hypertension].

PMID- 9280536
TI  - [Morphological changes in dogs liver during altitude adaptation].

PMID- 9280537
TI  - [Effect of laser radiation on rats uterine capillaries during folliculin
      injections].

PMID- 9280539
TI  - Protocol for the rehabilitation after hip fractures in the elderly.

PMID- 9280540
TI  - Biomarkers, low-dose carcinogenesis and dietary exposures.

PMID- 9280541
TI  - Annual meeting of the Hungarian Biochemistry Society, Drug Biochemistry Section.
      May 29-31, 1996. Abstracts.

PMID- 9280542
TI  - [In utero cellular therapy].

PMID- 9280543
TI  - [Super radical surgery of advanced ovarian cancers (stages III and IV)].

PMID- 9280544
TI  - [Severe anal incontinence: treatment by implantation of an artificial anal
      sphincter].

PMID- 9280545
TI  - [Pregnancy in women over forty years old].

PMID- 9280546
TI  - [Should fetal reduction be used in triplet pregnancies?].

PMID- 9280547
TI  - [Antibiotics in obstetrics].

PMID- 9280548
TI  - [Preoperative examinations: the essential and the superfluous].

PMID- 9280549
TI  - [GnRH analog protocols revisited I--advantages and doubts].
AB  - During the last decade, the introduction of GnRH analogs in ovarian stimulati on
      protocols has greatly improved the outcome of IVF cycles. Through a suppressive
      effect of hypophyseal secretion, GnRH analogs have allowed to prevent cycle
      cancellation related to endogenous LH surge and/or premature luteinization.
      Nevertheless, apart from this beneficial effect, little information has been done
      about consequences of their administration on residual gonadotroph secretion,
      ovarian responsiveness to gonadotrophins, quality of oocyte and conceptus,
      endometrial receptivity. The extreme diversity of long-term and short-term
      protocols used in clinical practice makes this analysis more difficult. In the
      first part of this review, the authors examine the several ways of GnRH analogs
      prescription in order to separate their specific effects on each reproductive
      function component.

PMID- 9280550
TI  - [Ectopic pregnancy recurrence: role of gynecologic, obstetric, contraceptive and
      smoking history].
AB  - The purpose of this study, based on data from the register of ectopic pregnancy
      in Auvergne (centre of France), is to identify risk factors of recurrence of
      ectopic pregnancy (EP). The social characteristics, gynaecological, surgical and
      reproductive history and conditions of the conception of 96 women with a previous
      EP were compared to those for 566 women without previous EP. Risk factors
      associated with the management of the first EP could not be analysed with the
      data available. Several factors increased the risk of recurrence: previous proved
      or suspected salpingitis (OR = 3.6), maternal smoking (OR = 1.7 to 2.0 according
      to the consumption level), maternal age greater than 30 (OR = 2.0), and previous
      recurrent spontaneous abortions (SA) among childless women (OR = 3.4 to 11.9
      according to the number of SA). The last of these factors may reflect another
      unknown risk factors common to recurrent SA and recurrent EP (for example
      hormonal or karyotype factors). Previous use of intra uterine device is
      associated with a decrease in the risk of recurrence of EP (OR = 0.27), but this
      contraceptive method should be considered as an indicator of good fertility
      rather than as a protective factor for EP recurrence.

PMID- 9280551
TI  - [Controlled hyperstimulation in intra-uterine inseminations: hMG-hCG protocol
      (204 cycles)].
AB  - OBJECTIVE: to evaluate the results of superovulation, protocol hMG-hCG,
      associated to IUI for treatment of infertility. PATIENTS AND METHODS: this
      prospective study, includes 77 couples who underwent 204 consecutive cycles of
      homologous IUI. The same protocol was applied for all the couples. hMG was
      administrated from cycle days 2 to 5 (3 then 2 ampuls per day). Patients were
      monitored daily, by evaluation of serum oestradiol. Insemination was done 36 to
      38 hours after hCG injection. RESULTS: 2.6 cycles were done per couple. We
      observed 16.2% pregnancy per cycle. The best results were obtained in female
      indications, in the first cycle, with more than 500,000 spermatozoide and with a
      level of E2 between 500 and 1500 pg/ml. Multiple pregnancy was observed in 18.2%.
      CONCLUSION: controlled ovarian stimulation should be associated to all IUI.

PMID- 9280553
TI  - [Beautifying the breast].
AB  - Preoperative, psychoanalytically oriented evaluation can reveal hidden needs
      behind the request for esthetic breast surgery. When this become evident for the
      patient, the surgical project is modified considerably by the evaluation, or
      afterwards by way of psychotherapy. Sometimes the desire of surgery is replaced
      by psychotherapy and the projet of mammaplasty is abandonned.

PMID- 9280552
TI  - [Comparative study of the acceptability of a new estradiol Tx 11323 (A) gel and a
      transdermal matrix system].
AB  - OBJECTIVE: to compare the acceptability of a new estradiol gel TX 11323 (A) and a
      transdermal matrix system. METHOD: this randomised open crossed study was
      conducted on 80 healthy menopausal female volunteers treated successively with
      1.5 mg of estradiol per day in gel form (Estreva Gel, Theramex, Monaco) and by a
      transdermal matrix twice-weekly system delivering 50 micrograms/24 h of estradiol
      (Oesclim 50, Fournier, Dijon-France). The treatment was applied for 25 days with
      an interval of 6 days between the 2 administration cycles. Acceptability was
      evaluated and compared by a self-questionnaire given on D1 and D25 of each
      therapeutic cycle. RESULTS: the 2 treatments, after 25 days of use, were judged
      convenient, easy and fast to use by more than 90% of subjects. There was,
      nevertheless, a significant difference in favour of the gel in respect of the
      estimation of the "visual aspect" of the treatment, reported skin problems,
      problems with application technique, as well as discomfort during intimacy found
      in 11% of cases using the transdermal system. It is noted that 80% of the women
      consider the gel treatment more feminine (p < 0.001) and that 61.3% prefer this
      treatment compared to 32.5% preferring the transdermal system studied (p =
      0.005). CONCLUSION: this study shows a better acceptability of the estradiol gel
      TX 11323 (A) compared to that of the transdermal matrix system studied.

PMID- 9280554
TI  - [Practical gynecology in the African bush: from humanitarianism to humanism].

PMID- 9280555
TI  - SGOT, LDH, HBD, CPK, CK-MB, MB1MB2, cTnT, cTnC, cTnI.
AB  - The troponin assay is the "new kid on the block." cTnI is currently the most
      sensitive, specific marker for cardiac damage and will replace the other less
      specific cardiac markers. This is a result of continued search for measures that
      provide the earliest diagnosis, which in turn ensures the greatest positive
      influence on morbidity and mortality in acute MI. Is the cTnI assay the ultimate
      marker for cardiac injury? It is doubtful. Only time will tell.

PMID- 9280556
TI  - [Platelet activating factor and bronchial asthma. Is it relevant?].

PMID- 9280557
TI  - [Comparative study of acute and chronic forms of pleural tuberculosis].
AB  - To analyze whether a characteristic pattern distinguishes acute forms (symptoms
      starting no more than one week earlier) and subacute or chronic forms (symptoms
      lasting more than one week) of pleural tuberculosis (PT) in our practice.
      Retrospective analysis of 102 cases of PT diagnosed between 1986 and 1992,
      comparing the findings of case histories, imaging, pleural biochemistry and
      cytology, microbiology of sputum, pleural biopsy and fluid, anatomy and pathology
      studies of the biopsy specimens, course of disease, response to treatment and
      sequelae after one year and a half. Thirty-two patients (31.4%) had acute PT and
      70 (68.6%) had chronic forms. LDH levels and the percentage of pleural nuclear
      polymorphism were higher in acute cases, while the concurrence of systemic
      involvement and lymphocytic predominance was more often seen in chronic cases.
      Other data analyzed were similar in both groups. No specific clinical or X-ray
      profiles or differences in course of disease and response to treatment
      distinguishes between acute and chronic forms of PT after 7 days. Only LDH levels
      and cytology results differentiated acute forms and, occasionally, such cases
      were indistinguishable from pneumonia-like effusion.

PMID- 9280558
TI  - [Chylothorax secondary to blunt thoracic trauma. Report of 6 cases].
AB  - Chylothorax is a rare condition that even more rarely arises as a result of
      closed thoracic trauma. We report a series of 6 patients who suffered chylothorax
      after closed trauma, who were diagnosed early and treated conservatively. Either
      total parenteral feeding or adjusted enteral feeding, depending with
      circumstances, was started early such that complications from chylothorax were
      few. Surgery was required in only one case, and outcomes were satisfactory in all
      patients, none of whom died.

PMID- 9280560
TI  - [Treatment of asthmatic crises at a hospital emergency service. Are the protocols
      followed?].
AB  - Improper assessment and treatment of asthma attacks have been identified as
      causes of increased morbidity and mortality: several pneumological societies have
      therefore created and published guidelines for facilitating decision making and
      for preventing unnecessary failures of therapy. The objective of this study was
      to examine emergency department compliance with such guidelines in our hospital,
      comparing the performance of pneumologists and other specialists. We reviewed the
      records of 117 patients treated for acute asthma attacks in 1994 (87 women and 30
      men, mean age 46 years); 37 patients were treated by pneumologists and 80 by
      other specialists. The two physician groups differed significantly with respect
      to initial assessment of severity, particularly in the recording of vital signs
      (p < 0.05) and in the examination of some signs such as the use of accessory
      musculature (38% versus 10%, for pneumologists and other specialists,
      respectively) or the presence of cyanosis (81% versus 55%). Other factors
      associated with risk of death were noted only occasionally. Peak flow meters were
      used with only 5 patients, all examined by pneumologists; on the other hand,
      arterial blood samples for gasometric measurements were taken from 97%, although
      only 24% met the criteria stipulated in the guidelines. Treatment evaluated
      against the guidelines was incorrect in 24%, with no significant differences
      between pneumologists and other specialists. We conclude that: 1) the emergency
      clinical assessment and treatment of patients presenting with acute asthma attack
      is inadequate for a large proportion of patients, as the recommendations of
      consensual guidelines are habitually ignored, and 2) although there are
      differences in the management of these patients by pneumologists and other
      emergency room specialists, the former do not generally do a better job of
      following the guidelines.

PMID- 9280559
TI  - [Long-term effects of nasal continuous positive airway pressure on ventilatory
      patterns of patients with obstructive sleep apnea syndrome].
AB  - We studied 20 patients with obstructive sleep apnea syndrome (OSAS)
      prospectively, before and after administering continuous positive airway pressure
      through a nasal mask (CPAPn) at night for 10 months, with the aim of determining
      the effects of ventilatory pattern of long-term treatment with CPAPn in OSAS
      patients. The following data were collected for all patients: anthropometric
      variables, lung function test results, arterial gasometric readings at rest,
      oxygen alveolar-arterial differential [Dif(A-a)O2)], central respiratory function
      variables at rest and during hypercapnic stimulus. Mean duration (range) of
      treatment with CPAPn was 12.5 (10-18) months. We observed a significant increase
      in PaO2 (p = 0.01) and a decrease in PaCO2 (p = 0.02) with slight variations in
      body weight and no changes in lung mechanics or in Dif(A-a)O2. The ventilatory
      pattern at rest showed an increased in VE and in respiratory frequency (p =
      0.0003 and p = 0.033, respectively) with non significant changes in VT. The VT/Ti
      ratio increased (p = 0.015) and P0.1 decreased slightly (p = 0.025). We found no
      significant changes in the CO2 response slopes of VE or P0.1. In conclusion,
      CPAPn improves hypoxemia and hypercapnia in OSAS patients, above all by
      increasing baseline basal ventilation. The exact mechanisms implicated are poorly
      understood, but our data suggest a certain direct or indirect effect on
      respiratory muscles, reducing muscle fatigue, thus favoring greater availability
      during sleep.

PMID- 9280562
TI  - [New prospects in cystic fibrosis treatment].
AB  - Only a few years ago, cystic fibrosis (CF) was considered the most frequent
      genetic disease in childhood, although survival has increased considerably in
      recent years owing to improved treatment. We discuss treatments that are still
      relevant as well as others that are under investigation now, aiming for better
      understanding of the disease and the therapies that have improved quality of life
      for CF patients.

PMID- 9280561
TI  - [Hospital admissions related to lung disease in Andalucia: 1993-1994].
AB  - To determine the pneumological causes for hospital admission in Andalucia (Spain)
      and thereby improve knowledge of respiratory morbidity. From the Combined Minimum
      Data Base on admissions to Andalusian hospitals for 1993 and 1994, adjusted to
      the CIE-9-MC coding system, we analyzed main diagnoses registered. Cases with
      respiratory involvement were obtained, excluding patients under 7 years of age.
      Admissions for pneumological causes accounted for 6.3% of all admissions, with a
      total of 314 diagnostic categories, although 98.5% of all admissions were related
      to only 139 diagnoses. The 53 most frequent diagnostic categories accounted for
      93% of patients and 55.2% of admissions were related to only 10 causes and led to
      54.16% of all stays for pneumological diseases. Categories 486 and 481
      (pneumonias), along with 496, 491.2 and 491.21 (diseases involving chronic air
      flow obstruction) were the most often used. Respiratory problems account for
      6.23% of all hospital admissions in Andalucia, with lung infections and
      conditions falling under the category of chronic obstructive pulmonary disease
      being by far the most frequent pneumologically related reasons for
      hospitalization. The precise interpretation of diagnostic categories needs to be
      better defined in the coding system.

PMID- 9280563
TI  - [The use of arsenic in various respiratory diseases].

PMID- 9280564
TI  - [Skin tumor as presentation form of lung actinomycosis].
AB  - We report three cases of thoracic actinomycosis whose symptoms were cutaneous
      tumors on the thorax. Clinical signs and images are described, along with
      diagnostic procedures. The excellent outcome after antibiotic treatment, which
      must last at least 6 months, is emphasized as well as the need to keep this
      disease in mind when certain symptoms and images coincide.

PMID- 9280565
TI  - [Intrabronchial foreign body in adults: usefulness of computerized tomography].
AB  - The diagnosis of intrabronchial solid foreign body is recorded less often in
      adults than in children and becomes increasingly difficult to make as time passes
      after aspiration. Three cases of intrabronchial foreign body in adults with no
      history of loss of consciousness are reported. Clinical and radiological features
      are discussed, with special mention of the diagnostic role of computed
      tomography, a technique that has not often been mentioned in the literature on
      foreign body aspiration, but that is more sensitive and specific than the simple
      X-ray. In patients with symptoms inconsistent with X-ray images, computed
      tomography can be a useful, noninvasive technique for guiding diagnosis and
      assessing the need for bronchoscopy.

PMID- 9280566
TI  - [Hydropneumothorax in Eikenella corrodens infection].

PMID- 9280567
TI  - [Ambulatory oxygen therapy via transtracheal catheter].

PMID- 9280568
TI  - [The exercise bronchoconstriction test in the hyperreactive sports players and
      its report].

PMID- 9280569
TI  - Controversies in palliative radiotherapy. Proceedings of a meeting. Toronto,
      Canada, April 1995.

PMID- 9280570
TI  - Urogynaecology proceedings of the joint RCOG/BAUS urogynaecology meeting. 19
      September 1996.

PMID- 9280571
TI  - Despite progress women in academic medicine find glass ceiling still in place.

PMID- 9280572
TI  - [Medical and social problems of the disabled and persons of retirement age in the
      Perm region].
AB  - The parameters of the health status of residents of the Perm region are analyzed.
      The number of invalids was found to increase annually. The activities of the
      administration of the region aimed at solution of problems related to disease
      prevention, therapy, and rehabilitation of disabled subjects are discussed.

PMID- 9280573
TI  - [State and prospects of demographic processes in the Udmurt Republic].
AB  - Analyzes the time course of demographic indices in Udmurtia in recent years.
      Socioeconomic measures are offered, aimed at deceleration and arrest of the
      depopulation process.

PMID- 9280574
TI  - [Health status and life styles of young people].
AB  - Comprehensive sociohygienic investigation of the health status and life style of
      young people in the town of Chelyabinsk showed numerous unfavorable tendencies
      and serious defects in the present-day health status, life style, reproductive
      function and readiness of young people to work, this having a negative impact on
      the "quality" of working resources of the country and on the formation of the
      demographic situation in the country. A state program of health support and
      formation of healthy life style and reproductive purposes in young people is
      necessary, the more so that the growing socioeconomic instability in the country
      creates conditions for the intensification of negative tendencies.

PMID- 9280575
TI  - [Current problems of health protection of inhabitants of a large industrial
      center in West Siberia].
AB  - Presents the results of three-year study of the factors determining population
      health under new conditions of market relations and transfer to the medical
      insurance system in West Siberia. Offers recommendations aimed at improvement of
      organization of medical care at the present-day status of economy and health
      care.

PMID- 9280576
TI  - [Consumer of health services as a subject of the public health system].

PMID- 9280577
TI  - [Differential criteria and classification of traumatisms at home].
AB  - Communal traumatism represents a heterogeneous phenomenon in whose structure
      latent, outpatient, hospital, invalidating, and lethal communal traumatism should
      be distinguished. The said types of traumatism differ by the incidence, share,
      mean age of the victims, predominating type of injuries, share of multiple
      injuries, time of application for primary health care, share of ambulance calls,
      percent share of invalidity, type and duration of invalidity, and outcome of
      injury. The severity of communal traumatism gradually increases from the first to
      the last named type and depends on the type of injury and development of
      complications.

PMID- 9280578
TI  - [Morbidity of athletes].

PMID- 9280579
TI  - [Ways of improving the organization and management of regional public health].

PMID- 9280580
TI  - [Experience in organizing hospice service in a large city].
AB  - Analyzes the current models of the hospice service organization in St.
      Petersburg. Critical analysis of the service permits a conclusion that model 2 of
      this service organization is preferable.

PMID- 9280581
TI  - [Mechanism of differentiated work payment under conditions of intensified medical
      activities].
AB  - A mechanism of differentiated payments to all categories of workers of forensic
      medical expert evaluation bureaus with consideration for the final results of
      expert activity has been developed. The quality and terms of expert evaluations
      have markedly improved at the expense of differentiation in work payment.

PMID- 9280583
TI  - [Continuous system of postgraduate education of physicians in Udmurt Republic].
AB  - Presents the experience gained by the Izhevsk Medical Institute in two-year
      training of general practitioners (family physicians): versatile training
      programs have been developed, as well as individual legislative problems. The
      program is supplied with training and therapeutic base.

PMID- 9280582
TI  - [Experience, problems and prospects in training of bioengineer personnel].

PMID- 9280584
TI  - [Public health institutions under conditions of market economics].

PMID- 9280585
TI  - [Analysis of history of medicine].

PMID- 9280586
TI  - [Works of G. A. Batkis and current problems of social medicine (on the 100th
      anniversary of the birth of the scientist)].

PMID- 9280587
TI  - [Medical staff: from the history of medicine in Russia in the 18th century].

PMID- 9280588
TI  - [Morbidity and characteristics of medical care of disabled persons].

PMID- 9280589
TI  - [Pages from the history of Russian military-field surgery].

PMID- 9280590
TI  - [Hospital for Russian soldiers on the island of Kefallinia (1802-1807)].

PMID- 9280591
TI  - [Perinatal encephalopathy: leading disease of children in the 1st year of life
      and its medical-social consequences].
AB  - The morbidity of infants during the first year of life as regards individual
      states developing in the perinatal period varies in some towns within 100
      200/1000. One of the major conditions of this class is perinatal encephalopathy.
      The total morbidity among infants of the first year of life suffering from
      perinatal encephalopathy is two times higher than that of infants without
      abnormalities of the central nervous system. At the age of 4 the morbidity values
      in these two groups are 3230.9 and 2194.2/1000, respectively.

PMID- 9280592
TI  - [Features of present-day contraception behavior (according to the data of the
      Tver district)].
AB  - Presents the results of a random social hygienic study devoted to family
      planning, carried out in the town of Tver and its region. The objects of this
      study were medical and university students and physicians specialized in
      obstetrics and gynecology engaged in family planning problems. Contraception
      behavior of young people was analyzed and the structure of contraception in
      Russia compared with that in countries with well-developed economy. Family
      planning problems viewed by present-day young people are discussed: the optimal
      marriage age and time of appearance of the first baby, the desired number of
      children, intergenetic intervals, and pregnancy outcomes. The attitude of
      obstetricians and gynecologists to contraception, their knowledge and skills in
      this sphere are analyzed. Shortcomings in the activities of obstetrical and
      gynecological service in family planning and contraception are discussed.

PMID- 9280593
TI  - [Organization of staff and its and management in public health: postgraduate
      training].
AB  - Validates the necessity of specialized postgraduate training of public health
      administrators and staff managers in the sphere of public health staff
      management. Presents methods of organizing courses for advanced training of head
      workers and staff managers in public health and the experience gained in training
      at specialized courses.

PMID- 9280594
TI  - [New social contract in the countries of former Soviet Union].

PMID- 9280595
TI  - [Characteristics of medical-demographic processes in rural regions of Russia].
AB  - The serious medico-demographic problems of the last decade had a most negative
      impact on the rural population. A negative natural increment and a high level of
      aging of the rural population were evident as long ago as in the seventies. The
      number of children born to unmarried mothers is traditionally higher in villages,
      and the expected life span is lower there than in towns. Mortality caused by
      injuries, respiratory diseases, and infections, including the mortality of
      infants aged under one, is higher in the country than in towns. Urgent reasonable
      sociodemographic policy is needed to preserve the population of Russia, including
      its rural population.

PMID- 9280596
TI  - [Comments on the article by James A. Rice, "New social contract in the countries
      of former Soviet Union"].

PMID- 9280597
TI  - [On the way to public health reform].

PMID- 9280598
TI  - [New role of public health administration organs].

PMID- 9280599
TI  - [Public health under conditions of transition to market economics].

PMID- 9280600
TI  - [Development of health care of the urban population under new economic
      conditions].
AB  - Presents a model of reorganization of medical service for the urban population
      under novel economic conditions, which is effective from economic, medical, and
      social viewpoints. The model is based on the family medicine principle and
      provides the creation of an effective system of disease prevention, consisting in
      dynamic follow-up of the health status of the population in the Ukraine.

PMID- 9280601
TI  - [Diagnosis-related groups: a comparative analysis of hospital activity in
      different countries].
AB  - Comparative study of hospital activities in the Novgorod district and nine
      countries of the European Community, carried out within the framework of the
      International Project CAMISE (Case Mix and Severity) of the European Community on
      the basis of the classification system for diagnosis-related groups, showed a
      lower Case Mix Index, a longer hospital stay for all major disease, and a lower
      surgical activity in the hospitals of the Novgorod district in comparison with
      other European countries. The detected differences are largely due to specific
      features in the organization of hospital service in Russia (no special hospitals
      for acute and chronic patients, no nursing homes) and insufficiently intensive
      therapeutic and diagnostic process.

PMID- 9280603
TI  - [Development of obligatory health insurance in the Kemerovo district].
AB  - Analysis of published data, foreign experience, and consultations with prominent
      foreign experts helped create the legislative basis for budget and insurance
      provision for the formation of medical insurance structure in the town of
      Kemerovo and helped develop instructions and recommendations on interactions
      between treatment-and-prophylactic institutions, public health organs, and
      medical insurance organizations.

PMID- 9280602
TI  - [Assessment of the indicators of organizational activities of dental polyclinics
      in Moscow].
AB  - Presents the method of comprehensive probability assessment of a number of
      indexes calculated on the basis of the data derived from annual reports of 36
      dental clinics of Moscow for 1994. Correlations between the indexes and their
      signal deviations from the mean values were assessed and their integration and
      ranging carried out. This confirmed the possibility of a more effective
      utilization of reported data in adopting the managerial solutions and improvement
      of the medical and technological process.

PMID- 9280604
TI  - [The date of foundation of the Medical Department of the Moscow University].

PMID- 9280605
TI  - [Social-hygienic problems of family in the Extreme North].
AB  - Comprehensive socio-hygienic study of the health status and communal conditions
      carried out in the families in the Sakha Republic (Yakutia) which is
      characterized by specific economic and geographic features, uneven density of
      population in various regions, and peculiar medico-demographic tendencies brought
      the authors to a conclusion that a staged approach is needed to transfer to the
      family doctor organization of therapeutic and prophylactic care of the
      population.

PMID- 9280606
TI  - [Clinical application of interleukin-6 receptor antibody].
AB  - Interleukin-6 (IL-6) is a pleiotropic cytokine which shows multiple biological
      functions. Pathological significance of IL-6 has been elucidated in various
      diseases including multiple myeloma, Castleman's disease, and rheumatoid
      arthritis. Thus the blockade of IL-6 signal transduction may be therapeutically
      effective for these diseases. For this purpose, humanized anti-IL-6 receptor
      antibody was prepared, and its therapeutic efficacy has been examined.
      Immediately after administration of humanized anti-IL-y receptor antibody to the
      patients with multiple myeloma, fever and systemic edema disappeared followed by
      the stability of M-protein which had been rapidly increased before the treatment.
      Humaniged anti-IL-6 receptor antibody also improved not only the chronic
      inflammatory symptoms but also laboratory findings such a hemoglobin, C-reactive
      protein, erythrocyte sedimentation rate observed both in Castleman's disease and
      in rheumatoid arthritis. The data suggest that the blockade of IL-6 signal
      transduction can be a new therapeutic approach based on the pathological
      significance of IL-6 in these diseases.

PMID- 9280607
TI  - A review of interferon immunogenicity. Based on a roundtable workshop held in
      London, United Kingdom, 9 February 1996.

PMID- 9280608
TI  - [Class I and II histocompatibility antigens and severity of the alcoholic liver
      lesion].
AB  - The association between the class I and class II histocompatibility antigens
      (HLA) and the severity of alcoholic liver disease was studied in 102 alcoholic
      patients (64 males and 38 females) with liver disease. According to histologic
      diagnosis 41 patients had a mild hepatic lesion (12 with minimum changes, 15 with
      steatosis and 14 with fibrosis) and 61 patients had severe hepatic lesion (13
      with alcoholic hepatitis, 35 with cirrhosis and 13 with cirrhosis and alcoholic
      hepatitis). No differences were found between the two groups in regards to sex,
      quantity and length of alcohol consumption, although the patients with mild
      hepatic lesion were younger than those with severe hepatic lesion (41.2 +/- 8.2
      and 47.8 +/- 11.6 years, respectively). The prevalence of the A30, B16, B47,
      Bw56, Cw1, Cw5 and Cw7 antigens was higher in the alcoholics than in the
      controls, although only the A30 (12.7% vs. 4.4%, p < 0.04) and the Bw56 antigens
      (3.9% vs 0.1%, p < 0.001) remained significant when the p value was corrected by
      the number of antigens studied. These differences were due to a greater
      prevalence of the A30 antigens (17.0% vs. 4.4%, p < 0.001), B16 (24.3% vs. 7.5%,
      p < 0.01) and Bw56 (7.3% vs 0.1%, p < 0.001) in patients with mild hepatic lesion
      versus the controls. In contrast, these antigens were present in similar numbers
      in patients with severe hepatic lesion and in the controls. On the other hand, no
      differences were observed regarding the prevalence of the class II HLA antigens
      between the alcoholics and the controls, or between the two alcoholic groups.
      These data suggest that the alcoholics with A30, B16 and Bw56 antigens are less
      susceptible to developing severe liver disease.

PMID- 9280609
TI  - [Prevalence of monosymptomatic celiac disease in patients with iron deficiency
      anemia].
AB  - A prospective study of the prevalence of monosymptomatic celiac disease presented
      as ferropenic anemia in patients admitted for study such complication of was
      carried out. All the patients were evaluated by gastroscopy and biopsy of the
      distal duodenal segment, regardless of endoscopic appearance. Patients presenting
      an endoscopic lesion clearly suggestive as the origin of the chronic bleeding
      were excluded from the study. The prevalence of celiac disease, the only
      manifestation of which was ferropenic anemia, was 3.3% in this series. What is
      important to note in this study is the importance of duodenal biopsy in the study
      of ferropenic anemia, with the aim of avoiding diagnostic delay of a possible
      monosymptomatic celiac disease as the cause of the anemia.

PMID- 9280611
TI  - [Thromboembolic complications in inflammatory bowel disease].
AB  - Thromboembolic complications during the course of inflammatory bowel disease are
      infrequent but are mainly found in young patients and are associated with a high
      morbimortality. The etiopathogenesis of these complications has been widely
      debated and the existence of coagulation alterations and fibrinolysis have been
      suggested. Nonetheless, the mechanism must be complex since not only do not all
      the patients with these alterations present this complication but neither do all
      the patients with thromboembolism have recognized coagulation disorders. The most
      common clinical presentation is deep vein thrombosis with pulmonary embolism with
      arterial thrombosis being rare. Five patients with Crohn's disease and two with
      ulcerative colitis who presented a total of new thromboembolic episodes, six
      arterial (1 in primitive iliac artery, 1 in common femoral artery, 1 in humeral
      axillary artery, 2 in internal carotid and 1 in superior mesenteric artery) and
      three of venous localization (1 in brachyocephalic-subclavian trunk, 1 axillary
      and 1 iliac-femoral/pulmonary thromboembolism) are reported. An updated review of
      the etiopathogenesis, presentation, treatment and prophylaxis of the
      thromboembolic complications of inflammatory bowel disease is presented.

PMID- 9280610
TI  - [Menetrier disease associated with ulcerative colitis. Response to the treatment
      with octreotide. Review of the diagnostic criteria and etiopathogenesis].
AB  - The case of a patient with Menetrier's disease in association with inactive
      ulcerative colitis of 7 years of evolution is presented. Diagnosis was confirmed
      by exploratory laparotomy and the symptoms of anemia and hypoproteinemia improved
      following treatment with octreotide. On review of the literature this was found
      to be the third case of Menetrier's disease associated with ulcerative colitis
      described in the world literature. A possible relationship with an increase in
      alpha TGF is suggested. The diagnostic criteria and the possible etiopathogenic
      factors of the disease are herein reviewed.

PMID- 9280612
TI  - [Duodenal adenocarcinoma in celiac disease with late diagnosis and treatment].
AB  - It seems to be a link between small intestine cancer and celiac disease. We
      describe here a patient who developed a duodenal carcinoma fifteen years after
      the celiac disease diagnosis. Tumor endoscopic study and biopsy sampling are the
      more useful diagnostic approach. This is usually difficult because the lesion is
      very small or there are rests of food biding the lesion. Poor clinical layout and
      a later diagnosis favour the development of metastasis. A wide segmental
      resection including lymph nodes is the best therapy for tumors of the second and
      third duodenal segments.

PMID- 9280613
TI  - [Cholestatic hepatitis caused by amoxycillin-clavulanic acid. Report of a new
      case].
AB  - Toxic hepatitis is an infrequent secondary effect of amoxycillin-clavulanic acid
      with fewer than 30 well documented cases in the literature. Presentation is
      usually that of acute cholestasis several weeks after the initiation of treatment
      with this antibiotic. A new case of hepatic toxicity by amoxycillin-clavulanic
      acid is reported in a 47-years-old male who had taken this drug for a diarrhea
      syndrome. A brief review of the literature is made with special emphasis on the
      anatomopathologic aspects.

PMID- 9280614
TI  - [Histologic diagnosis of chronic hepatitis, grading and staging].

PMID- 9280615
TI  - [Cryoglobulinemia and hepatitis C virus].

PMID- 9280616
TI  - [Defense mechanisms of the gastric mucosa: functional bases and pharmacologic
      action].

PMID- 9280617
TI  - [Bone metabolic disease associated with celiac disease].
AB  - Patients with celiac disease present a high prevalence of osteopenia and
      osteoporosis which globally jeopardize the skeleton. The pathogenesis of this
      bone disease is related to an accelerated bone change in which catabolism
      predominates. The metabolic studies coincide in a negative calcium balance with
      consequent secondary hyperparathyroidism. Diagnosis requires evaluation of bone
      mineral density by precise, reliable methods to which all adult celiac patients
      should be submitted. Finally, specific treatment with a gluten-free diet leads to
      significant bone remineralization.

PMID- 9280618
TI  - [Non-alcoholic steatohepatitis: a controversial cause of liver cirrhosis].

PMID- 9280619
TI  - [A case of acute hepatitis E in Seville].

PMID- 9280620
TI  - [Jejunal perforation caused by a fish bone].

PMID- 9280621
TI  - [A case of primary hemochromatosis with normal blood ferritin].

PMID- 9280622
TI  - [Cerebrovascular disease in young women].
AB  - INTRODUCTION: Cerebrovascular disease is an important cause of morbi-mortality.
      Although its incidence is maximal in older groups, its incidence in young people
      cannot be forgotten, even more if we consider the socioeconomic and personal
      consequences derived from it. There are several works on this subject but few of
      them analyze the specific problem of stroke in women. There is some degree of
      controversy in this subject, specially about the role of several factors which
      are more prevalent or either exclusive for women. OBJECTIVES: We wanted to
      analyze the risk factors and clinical characteristics in a group of women under
      45 who suffered a stroke and also to compare these risk factors between women
      under 35 and those from 35 to 45. MATERIAL AND METHODS: We have carried out a
      descriptive study, including 61 women under 45 admitted to our centre
      consecutively between January 1989 and October 1996. RESULTS: Among the most
      prevalent factors we have found hypertension (27.8%), tobacco consumption (24.5%)
      and the presence of cardiac abnormalities (22.9%), specially associated to
      valvular pathology, as well as a higher incidence of contraceptives consumption
      in women under 35 (80%). CONCLUSIONS: These factors are similar to those found in
      studies on the general population of young people. Our data indicate that the
      relevance of the main factors for stroke is common for both sexes and is also
      significant in young patients.

PMID- 9280623
TI  - [Epidemiology of cerebrovascular diseases in Sabaneta, Colombia (1992-1993)].
AB  - INTRODUCTION AND OBJECTIVES: In Columbia the epidemiology of cerebrovascular
      illness (ECV) is unknown. For this reason a study was made to determine the
      prevalence, incidence and annual mortality, and to identify the different types
      of ECV and the demographic characteristics of the population. MATERIAL AND
      METHODS: In the urban area of Sabaneta, Columbia 13,588 door to door interviews
      were carried out among the inhabitants. A cutoff study carried out between April
      and June 1992 showed the prevalence of ECV. One year follow-up of persons without
      ECV between June 1992 and June 1993, enabled the incidence and annual mortality
      to be evaluated. A structured interview was used to identify the demographic
      characteristics of the population and classify people as healthy or as possibly
      having ECV. The latter were examined by neurologists to confirm or rule out the
      presence of ECV and to determine the type of ECV involved. Of the total urban
      population, 76.9% agreed to participate in the study. During the follow-up year,
      8.4% were lost trace of. RESULTS AND CONCLUSIONS: The prevalence of ECV was
      559.3/ 100,000 inhabitants, increasing with age (15). In the 15-40 year old
      group, the incidence of ECV was 44 times higher in women than in men. The annual
      incidence rate was 88.9/100,000 inhabitants: thromboembolic disease was the most
      frequent. Of a total of 87 cases of ECV, 12 (13.98%) died of various causes
      during the year in which they were being observed. The annual mortality rate for
      ECV was 16.2/100,000 inhabitants, all being primary cases.

PMID- 9280624
TI  - [Mental deficiency preceded by transitory hypertonic cerebral motor disorder].
AB  - OBJECTIVE: To analyse clinical and outcome features of patients with mental
      retardation and transient hypertonia in early life which lead to the diagnosis of
      hypertonic cerebral palsy. MATERIAL AND METHODS: We study six patients that
      presented with the above features in our neuropediatric out patients clinic.
      Clinical data related with the hypertonic signs and its evolution were collected.
      All the patients were assessed to find their present cognitive and development
      state. RESULTS: Clinical and radiological signs of a possible prenatal
      neurological damage were found in all the patients. Structural anomalies were
      presented in neuroimaging in five cases. Agenesia or hypoplasia of corpus
      callosum was the most common finding. The pattern of progression of this cases
      were: 1. Improvement of hypertonia with almost normal tone by the age of two
      years. 2. Despite of the resolution of motor signs, persistence of different
      degrees of mental retardation. CONCLUSIONS: Our reported patients presented a
      peculiar pattern of progression within the wide variability of the cerebral palsy
      group.

PMID- 9280626
TI  - [Measurement of intracranial pressure as a factor in the prognosis of the course
      of serious cranio-encephalic injuries].
AB  - We have analyzed the course and outcome in 100 consecutive cases with severe head
      injuries, all were treated in a uniform manner. Surgery was performed immediately
      in patients with extracerebral or intracerebral hematomas. Intracranial pressure
      (ICP) was monitored in all. Forty-five patients recovered with no or minimal
      neurological deficit, fifteen patients are moderately disabled, four are severely
      disabled and eight remain in a persistent vegetative state. The mortality was
      28%. The favourable outcome in this series suggests that control of intracranial
      hypertension with careful attention to medical complication can improve the
      outcome in patients with severe head injuries.

PMID- 9280625
TI  - [Clinical identification of hereditary ataxias. A study of 38 cases in Colombia].
AB  - INTRODUCTION: Hereditary ataxias are a complex group of degeneratives diseases of
      the CNS. Material and methods. We studied 38 patients who were diagnosed
      inherited ataxia according to recent classification and radiologic criteria. We
      proposed flow sheet in order to reduce the cost of the studies. RESULTS: The most
      frequent findings we encountered were the congenital ataxias and the late onset
      ataxia forms, olivopontocerebellar ataxias (OPCA) and the late cortical
      cerebellar ataxias (CCA), following were the Friedreich ataxias, the intermittent
      ataxias, and cerebellar ataxias with myoclonus. We found finally two
      multisystemic atrophies. We didn't find dominant inheritance in the late onset
      ataxias, some of these were recessive forms and the others could be the novo
      mutations or idiopathic cerebellar ataxias of adult onset. CONCLUSION: It would
      be appropriate to enlarge the studies in the metabolic and treatable forms and
      try to define the forms that have a known genetic mutation.

PMID- 9280627
TI  - [Contribution of thalamic somatosensory evoked potentials to stereotaxic
      thalamometry].
AB  - INTRODUCTION: In order to use short latency somatosensory thalamic evoked
      potentials (PES) to locate therapeutic targets in functional surgery, thalamic
      PES were recorded during stereotactic thalamotomy in 25 patients with Parkinson's
      disease, using a concentric bipolar semi-micro-electrode, 4 mm in diameter. In
      the 72 trajectories planned. 628 registers were made, obtaining 314 PES in 55
      trajectories. These recordings were divided into 5 groups, according to the
      electrical variables evaluated in each case (absolute latency, inter-peak
      latency, absolute amplitude and number of phases). MATERIAL AND METHODS: The
      electrophysiological characteristics of the PES groups obtained, and the spatial
      representation of these in a tridimensional system of coordinates, is shown. We
      analyze the sequence of the groups of potentials in each of the trajectories
      followed. CONCLUSIONS: We consider that the limit between adjacent nuclear edges,
      ventral intermediate (Vim)-ventro-caudal (Vc), may be represented by the
      transition of potentials in group 1 to potentials in group 4 and/or potentials of
      group 3 to those of group 2. This study shows that thalamic PES are useful for
      locating targets during stereotactic thalamotomy.

PMID- 9280628
TI  - [The clinical significance of auditory evoked potentials of the brainstem in
      neonates].
AB  - INTRODUCTION: Brainstem auditory evoked potentials (BAEP) are an objective test
      that provides an early detection of hearing losses and a functional evaluation of
      the auditory pathway. MATERIAL AND METHODS: All neonates born between November
      1989 and December 1994 presenting some factor of audiologic or neurologic failure
      were tested by ABR, in order to determine the prognostic significance of
      abnormalities on follow-up. RESULTS: Of 40 selected babies 17 did not pass the
      former test and were classified as follows: eleven in a peripheral hearing loss
      group of mild-moderate degree and 6 in groups of severe peripheral hearing loss
      or central disorder of the auditory pathway. CONCLUSIONS: On follow-up an ABR
      test was included disclosing that many of the mild-moderate peripheral
      abnormalities has a transitory nature. Infants included in the other two groups
      had a very poor outcome from the point of view of life expectancy and psychomotor
      development.

PMID- 9280629
TI  - [Clinical features of daily chronic headache].
AB  - INTRODUCTION: Although the International Headache Society considers chronic
      tension headache to be a chronic headache, patients with daily chronic headache
      may have pain which is not only due to tension but also has migrainous features.
      OBJECTIVE: To evaluate the clinical differences and abuse of drugs in a group of
      patients with chronic daily headache who were consecutively evaluated in the
      Neurology Clinic. MATERIAL AND METHODS: We consider the patients to have daily
      chronic headache when they have had pain at least 6 days a week for the past 6
      months. Using this criterion, we studied 112 patients, of whom 90 (80.4%) were
      women and 22 (19.6%) men. Results. Sixty nine (61.6%) had transformed migraine
      and 43 (38.4%) tension headache. There were no differences in their current ages
      but the age of onset of the headaches varied (p = 0.000,t). Unilateral pain,
      trigger factors and a family history were more frequent in the cases of
      transformed migraine. Eighty four patients (75%) abused analgesics. Although we
      found different pain intensities (p = 0.000, chi 2) there was no difference in
      the weekly consumption of analgesics (p = 0.64, t) in the mg/week of ergotamine
      (p = 0.96, t) nor in absence from work between the two types of headache.
      CONCLUSIONS: In spite of clinical differences between transformed migraine and
      tension headache, which may help diagnosis, in our series abuse of analgesics
      (including ergotamine) was a common characteristic.

PMID- 9280631
TI  - [Epileptic syndromes which show continuous spike and wake complexes during slow
      wave sleep].
AB  - INTRODUCTION AND OBJECTIVE: The association of cognitive and/or behavioral
      disturbances, epileptic seizures and continuous discharges spike-waves during
      slow sleep in the EEG, has been described in three epileptic syndromes:
      continuous spike-wave during slow sleep syndrome (CSWS), Landau-Kleffner syndrome
      (LKS) or acquired epileptic aphasia, and atypical benign partial epilepsy of
      childhood (ABPE). MATERIAL AND METHODS: We report 13 patients; two of these have
      been diagnosed of CSWS. four of LKS and seven of ABPE, according to the
      definition criteria. RESULTS: The main clinical features in each patient are
      presented here. In all patients, continuous spike-wave discharges were observed
      for more than > 80% of the total sleep period at some time during the course of
      the illness. There are many similarities at the age of onset, the occurrence of
      several types of seizures, the evolution and the electroencephalographic findings
      in awake state and sleep. CONCLUSIONS: It suggests that the CSWS, LKS and ABPE
      have probably the same pathophysiology and that they are the severe, moderate and
      benign forms of a single epileptic syndrome, age-related, with continuous spike
      waves and various neuropsychological and behavioral disturbances. The
      neuropsychological manifestations depend probably on the localization of the
      original epileptic focus.

PMID- 9280630
TI  - [Evaluation of the effect of long term valproic acid treatment on plasma levels
      of carnitine, ammonia and amino acids related to the urea cycle in pediatric
      epileptic patients].
AB  - INTRODUCTION: Valproic acid (VPA) is an antiepileptic drug widely used in
      paediatrics. In spite of being a safe and effective anticonvulsant, VPA has been
      involved in the onset of changes in the metabolism of ammonia and carnitine,
      although few prospective studies have been made of this. OBJECTIVES: To evaluate
      the effect of long-term VPA administration, particularly on the metabolism of
      carnitine, ammonia and plasma amino-acids and the possible clinical repercussions
      of this in a group of epileptic patients studied prospectively and
      retrospectively. MATERIAL AND METHODS: A study was made of 102 epileptic children
      on long term anticonvulsant treatment mainly with VPA. These patients were
      divided into two groups: group I (n = 25) were studied prospectively (basal
      sample, after one, six and twelve months of treatment) and group II (n = 77) or
      long term treatment group (a single sample extraction). In each epileptic patient
      and in 56 children from a control group (group III) studies were made of free
      plasma carnitine, ammonia and amino-acids related to the urea cycle and the
      plasma levels of each anticonvulsant drug. RESULTS: It was observed that in group
      I there was a fall in plasma carnitine concentrations with time and a progressive
      rise which was statistically significant (p = 0.001) in plasma levels, mainly of
      ammonia, glutamine, glycine and ornithine, from the basal levels to those after a
      year of treatment in practically 100% of the children studied. In group II
      children on antiepileptic drugs, mainly VPA, were seen to have lower plasma
      carnitine levels than those in the control group and higher serum ammonia,
      glutamine and glycine levels than the healthy population not treated with
      anticonvulsants. These differences were statistically significant (p = 0.001). No
      relationship was found between the parameters studied and the plasma levels of
      the drug, type of epilepsy or presence of side effects. CONCLUSIONS: These
      changes show the negative effects of VPA on the metabolism of carnitine and
      ammonia. It would therefore seem advisable to monitor these parameters in
      epileptic children on long term antiepileptic treatment.

PMID- 9280632
TI  - [Idiopathic partial epilepsy with occipital paroxysms].
AB  - INTRODUCTION: Partial benign epilepsy of childhood with occipital paroxysms (EPBI
      O) described by Gastaut in 1982, has been recognized in the latest Classification
      of Epilepsy and Epileptic Syndromes as being a form of idiopathic partial
      epilepsy. In 1989 Panayiotopoulos described a different form of idiopathic
      occipital epilepsy. OBJECTIVE: We analyzed the electro-clinical characteristics
      of EPBI-O in order to identify the different forms of idiopathic occipital
      epilepsy. MATERIAL AND METHODS: This prospective study included 74 patients who
      fulfilled the diagnostic criteria of EPBI-O. The patients were evaluated between
      January 1990 and June 1996 by means of clinical and electro-encephalic
      examinations during a follow-up period of between 6 months and 6.5 years.
      RESULTS: We identified two groups. Group I: eighteen patients with visual crises
      and post-ictal migrainous episodes, with or without motor crises, predominantly
      when awake and with the onset of these crises at 8.7 years old. On EEG there were
      P-O occipital paroxysms which reacted to eyelid opening and group II: fifty-six
      patients with crises of vomiting followed by oculo-encephalic version,
      predominantly during sleep and with an average age of 4.9 years when these crises
      started to occur. On EEG there were occipital spikes with identical morphology to
      that of the benign epilepsy of childhood with spikes of Roland (EPBI-R). Two
      patients had associated crises of EPBI-O of Group II and EPBI-R with independent
      occipital and Roland spikes. These formed a third group. CONCLUSIONS: This study
      confirms the existence of two variantes of EPBI-O; the 'Gastaut' type and the
      'Panayiotopoulos' type with a more benign and more frequent course.

PMID- 9280633
TI  - [A particular type of epilepsy in patients with congenital hemiparesis associated
      with polymicrogyria or unilateral pachygyria].
AB  - INTRODUCTION: Magnetic resonance has permitted the recognition of cortical
      dysplasias in patients with congenital hemiparesia and epilepsy. OBJECTIVE: To
      study the clinic-EEG characteristics and course of epilepsy in patients with
      congenital hemiparesia and unilateral polymicrogyria. METHODS AND RESULTS: We
      analyzed the clinical histories of 11 patients seen between 1990 and 1996. We
      studied 6 girls and 5 boys aged between 5 and 13 years, with a follow-up period
      of from 1 to 6 years. The epilepsy began at between 1 and 6 years old with
      partial motor seizures. On EEG there were frontotemporal spikes in 9 cases,
      temporooccipital in 1 and parieto-occipital in another. All 11 patients had
      hemiparesia, with slight mental retardation in 9 patients and moderate mental
      retardation in 2. The CT/MR brain scan showed unilateral polymicrogyria. At
      between 2 and 8 years of age, all 11 patients developed subintrant atonic crises
      with a pseudo-ataxic gait, absences in 7 patients and myoclonia in 3. Awake EEG
      showed bilateral asymmetrical spikes. During sleep 7 patients had continuous
      spikewave discharges and 4 had frequent asymmetrical bilateral spikes. Four
      patients relapsed. Five patients are free of crises, five have sporadic crises
      and one continues to have daily crises. CONCLUSIONS: These patients had
      hemiparetic cerebral paralysis, slight mental retardation and epilepsy. At about
      the age of 6 a peculiar electro-clinical condition developed. Response to
      treatment was satisfactory, although the follow-up period is still not long.

PMID- 9280634
TI  - [Cytomegalovirus retinitis in a pediatric AIDS patient].
AB  - INTRODUCTION: Cytomegalovirus retinitis (CMV) is the most frequently found
      opportunistic eye infection in adults with AIDS, with mean incidence of 20%-50%.
      However, only 5% of children with AIDS have this infection. CLINICAL CASE: We
      present the case of a six year old girl with stage C3 AIDS diagnosed at the age
      of 20 months, who developed unilateral diffuse retinitis due to CMV. The
      infection involved the posterior pole of the right eye, with retinal atrophy
      along the temporal vascular arcodes, and an active advance front in the temporal
      macula. The optic nerve was not found to be involved although the peripheral
      areas of the retina were involved leading to rhegmatogenous detachment of the
      superotemporal retina. In view of the systemic deterioration of the patient, no
      specific anti-CMV treatment was given. The patient died of respiratory
      insufficiency a few weeks later. CONCLUSIONS: CMV retinitis in paediatric AIDS
      patients is usually associated with more severe illness and a poorer general
      health than the adult population. In view of the absence of symptoms in these
      patients, periodic ophthalmoscopic examinations should be done in those who have
      severe immunological deterioration.

PMID- 9280635
TI  - [Internal ophthalmoplegia: a rare complication of varicella].
AB  - INTRODUCTION: Internal ophthalmoplegia complicating Chickenpox is rare. Fifteen
      cases have been reported so far. CLINICAL CASE: We reported a new case of this
      neurological complication in a 3 1/2 year old girl that 6 days after the onset of
      the typical rash, the right pupil was dilated and fixed to light and
      accommodation. Pupillary dilatation and accommodative paralysis persist after
      five years, but spectacle correction has restored the visual acuity.

PMID- 9280636
TI  - [Fragile X syndrome and mental retardation].
AB  - INTRODUCTION: Fragile-X syndrome is characterized by the presence of a fragile
      site (gap) on Xq 27.3 and the transcriptional inhibition of a mRNA protein
      binding gene called FMR-1. Neuropsychological features include cognitive
      impairment, attention deficit disorder with and without hyperactivity, and
      impairment of visuospatial functions, language and frontal executive functions.
      In the present paper, other cytogenetic and phenotype characteristics, associate
      disorders, neurological and neuroimaging studies are revised. CLINICAL CASES: We
      describe two siblings that illustrate the pattern of neurocognitive and
      behavioural trends of the Fragile X syndrome, and sex differences. DISCUSSION AND
      CONCLUSIONS: These two cases emphasize the need for performing a cytogenetic
      diagnostic in patients with mental retardation, of unknown etiology, and with a
      familiar history of mental retardation.

PMID- 9280637
TI  - [Carcinomatosis of the choroid plexus: clinical case and necropsy findings].
AB  - INTRODUCTION: Carcinomas of the choroid plexus are a rare malignant variety of
      papillary tumours which originate in the choroid plexus. Their occurrence in
      adults has been questioned because of the difficulty in differentiating them from
      the metastases of adenocarcinomas. CLINICAL CASE AND CONCLUSIONS: We present the
      case of a 57 year old man with a rapidly progressive illness characterized by
      disorientation, behaviour changes and amnesia, progressive deterioration of the
      level of consciousness until he was in deep coma and died (all within one month).
      There was no clinical evidence of the presence of a primary extra-cranial tumour.
      On magnetic resonance there was obliteration of the ventricular system with a
      protein material and thickening and increased marking of the ependyma walls,
      compatible with ventriculitis. Necropsy, limited to the skull, showed the
      presence of a malignant infiltrating tumour with papillary morphology, which
      affected the choroid plexuses of the whole ventricular system, infiltrated the
      adjacent nervous tissue and extended to the leptomeninges. These findings suggest
      a differential diagnosis between carcinoma of the choroid plexus and metastatic
      meningeal carcinoma.

PMID- 9280638
TI  - [Neurological manifestations of Paget's disease: presentation of one case and
      review of the literature].
AB  - INTRODUCTION: Paget's disease is a frequent metabolic disease. It is usually
      diagnosed as a accidental finding. Initial symptoms usually consist of
      generalized pain in bones. When it affects the Central Nervous System, symptoms
      usually appear in advanced cases and are due mainly to compression of the spinal
      cord. Neurological problems as the first manifestation of the disease are
      exceptionally found. CLINICAL CASE: We report the case of a woman affected by
      Paget's disease who presented as a triventricular obstructive hydrocephalus. The
      patient was 72 years old and consulted first to the emergency ward due to
      headache, gait disorders and cognitive abnormalities. COMMENTS: The most
      remarkable data about this patient are the indolent course of the disease which
      caused its debut as hydrocephalus associated to basilar impression, its
      favourable evolution after ventricular drainage and the almost absolute absence
      of previous similar cases reported in literature all over the last years.

PMID- 9280639
TI  - [Sarcoidosis: the presentation of a case with clinical features limited to the
      nervous system].
AB  - INTRODUCTION: Neurological pathology as the initial form of sarcoidosis is
      exceptional. Neurosarcoidosis represents 5% of all cases. Central nervous system
      involvement is more frequent in the acute forms of this illness, whilst myositis
      and peripheral neuropathy are more common in chronic sarcoidosis. CLINICAL CASE:
      A 60 year old woman presented with peripheral facial diplegia, diminished visual
      acuity and bilateral papilloedema, dysarthria and unsteady gait with left
      lateropulsion and paresia and dysesthesia of the distal parts of the limbs. X-ray
      and laboratory findings were normal. Gammography with Gallium 67 citrate showed
      mediastimal adenopathy. Neurographic study was compatible with mixed
      polyneuropathy and lumbar puncture showed aseptic meningitis. The diagnosis of
      neurosarcoidosis was confirmed by histopathological study of the skin and sural
      nerve. DISCUSSION AND CONCLUSIONS: When the presenting features of sarcoidosis
      are neurological, as in this case, diagnosis is difficult and pathology studies
      showing the presence of non-caseous granulomas are essential. Biopsy of the sural
      nerve may be very useful. Although the pathogenesis of sarcoid neuropathology is
      not completely clear, finding non-caseous granulomas associated with vasculitis
      in the nerve biopsy indicates that both disease processes may be involved in the
      peripheral nerve lesion.

PMID- 9280640
TI  - [Subarachnoid hemorrhage associated to subhyaloid hemorrhage: "Terson syndrome"].
AB  - INTRODUCTION: The combination of subarachnoid hemorrhage (SAH) and subhyaloid
      hemorrhage is known as 'Terson syndrome'. Retinal hemorrhage is commonly observed
      clinically in the optic fundi of patients with SAH, however, subhyaloid
      hemorrhage of the globe in the setting of SAH has been rarely on CT of the brain.
      Several mechanisms of subhyaloid hemorrhage have been proposed: a. A sudden
      increase in intracranial pressure (ICP) forces blood from the subarachnoid space
      directly into the preretinal space. b. A sudden rise in ICP is thought to
      decrease venous return to the cavernous sinus from the veins draining the globe.
      The increased retinal venous pressure results in stasis followed by vessel
      rupture. c. A sudden rise in ICP obstructs both the retinochoroidal anastomoses
      and the central retinal vein due to a rapid effusion of CSF through the
      communication of the subarachnoid space with the optic nerve sheat. This produces
      an acute decrease in venous drainage from the retina and results in stasis and
      hemorrhage. CLINICAL CASE: A 35 year old man, with a history of a non controlled
      arterial hypertension, dilated cardiopathy and 'agitation episodes'. He had a
      spontaneous intracranial hemorrhage, consistent in a parenchymal hematoma
      ruptured into ventricles and subarachnoid space. The CT showed through optic
      nerve sheath this hemorrhage extended to subhyaloid space. The patient came in
      coma 'depasse' and brain death. CONCLUSIONS: We report a case of Terson syndrome
      demonstrated by CT. This CT allow see the blood from the subarachnoid space erupt
      directly into the preretinal space through optic nerve sheath, confirming one the
      proposed mechanism for this syndrome.

PMID- 9280641
TI  - [Stiff-man syndrome. Presentation of a new case].
AB  - INTRODUCTION: The stiff-man syndrome (SPR) is a rare neurological condition
      characterized by the presence of marked, involuntary rigidity of the axial
      muscles and limbs, together with intense painful muscle spasms which
      characteristically occur following external stimuli such as sudden noises,
      brusque movements or emotional stimuli. Symptoms are markedly improved by sleep
      and by diazepam. The aetiology is unknown, although it is associated with certain
      auto-immune disorders, particularly diabetes mellitus (DM) and others such as
      thyroid disease, vitiligo, pernicious anaemia, adrenal insufficiency, etc. The
      presence of high titres of glutamate-decarboxylase (GAD) antibodies seems to
      indicate an auto-immune aetiology. CLINICAL CASE: We describe a 59 year old woman
      who complained of an illness starting seven years previously with progressive
      pain and contractions of the dorso-lumbar muscles, which later spread to the
      cervical and abdominal muscles and to the upper limbs. From the time of onset,
      there were exacerbations of the condition following external stimuli. Also there
      was generalized vitiligo and whilst this progressed, DM developed (which finally
      required insulin to control it). On EMG there was continuous muscular activity
      and absence of muscle relaxation. The presence of high titres of anti-nuclear
      antibodies, gastric parietal cell antibodies and anti-GAD was very marked. There
      was a spectacular response to treatment with diazepam, with progressive
      improvement although ever increasing dosage was required. CONCLUSIONS: A new case
      of the 'stiff-man' syndrome is presented and aspects of aetiopathology and
      treatment are reviewed.

PMID- 9280642
TI  - [Andermann syndrome: presentation of a case].
AB  - INTRODUCTION: Peripheral neuropathy with agenesis of the corpus callosum (or
      Andermann's syndrome) is a hereditary autosomal recessive disorder rarely found
      outside certain regions of Quebec Province (Canada). It is associated with mental
      retardation and various dysmorphic changes. Deterioration is usually progressive
      with loss of motor skills, development of scoliosis during adolescence, tendency
      to behaviour disorders and death during the third decade (approximately).
      CLINICAL CASE: We present a 13 year old girl diagnosed as having the spastic
      tetraparesic type of PCI, who was sent to us so that we could reconsider the
      diagnosis in view of the atypical course of the illness. The patient had an
      unusual phenotype with dysmorphic changes (mainly facial), axial hypotonia with
      flexion-retraction of the hands, generalized arreflexia, neurogenic bladder, skin
      changes with ulcers on the legs and mental retardation. Neurophysiological
      studies showed a predominantly motor polyneuropathy. There were signs of axonal
      neuropathy on both sural nerve and skeletal muscle biopsies. The clinical
      features, phenotype, microcephaly with agenesis of the corpus callosum and a
      posterior fossa cyst, associated with spinal atrophy indicated the diagnosis of
      Andermann's syndrome. CONCLUSIONS: This case is of interest in view of the
      exceptional rarity of Andermann's syndrome in our population.

PMID- 9280643
TI  - ["Locked-in" syndrome due to hyperglycemia].
AB  - INTRODUCTION: Hypoglycemia can cause a diffuse brain malfunction and sometimes a
      focal neurological deficiency, that could lead to a mistaken diagnosis of
      cerebrovascular disease. CLINICAL CASE: We describe the case of a 67 year old
      man, with diabetes mellitus type II treated with glibenclamide, that was referred
      to our hospital due to worsening of his chronic obstructive pulmonary disease. On
      the fifth day following admission he developed acute weakness in the right
      extremities and experienced difficulty in talking: six hours later he was
      conscious, with normal eye movements, but there was an absence of spontaneous
      facial motility and to pain; he showed complete cuadraplegia and bilateral
      Babinski. A determination of glycemia was made with the result of 24 mg/dl; after
      immediate treatment with glucose solution intravenously the patient recovered in
      a few minutes. CONCLUSION: This clinical observation reminds us of the importance
      of determining blood glucose in the assessment of any acute neurological
      dysfunction.

PMID- 9280644
TI  - [Mandibular neuropathy due to infiltration of the Gasser ganglion].
AB  - INTRODUCTION: The numb chin syndrome is characterized by oral and facial numbness
      restricted to the distribution of the mental nerve. This uncommon neuropathy has
      been described in association with a number conditions including malignant
      disease even in the patients no known to have cancer. Numb chin syndrome may be
      caused by metastatic involvement of the mental nerve, by involvement of the
      proximal mandibular root at the base of the skull or by intracranial
      leptomeningeal spread. CLINICAL CASE/DISCUSSION: We described a case of
      neuropathy of the chin as the initial symptom of the breast cancer. We suggested
      that the lesion was in the trigeminal ganglion based on enlargement and
      gadolinium enhancement of the trigeminal ganglia on MRI. A mental neuropathy
      should initiate a search for cancer that includes MRI of the head.

PMID- 9280645
TI  - [Intraventricular arachnoid cyst in the adult].
AB  - INTRODUCTION: Intracranial arachnoid cysts are benign, congenial cystic lesions
      found in infancy. The commonest sites are the lateral fissure and the posterior
      fossa. Exceptionally they may be found in the ventricular system. CLINICAL CASE:
      We describe a 69 year old patient with a clinical history of headache and
      tingling of the face for 24 hours. Diagnosis of a lateral ventricle arachnoid
      cyst was made on computerized tomography and magnetic resonance. Treatment was
      surgical with excision of the wall of the cyst and the communication with the
      ventricle. CONCLUSION: We review 14 cases previously described (9 adults and 5
      children), analyzing their clinical and radiological features, type of treatment
      given and the different theories proposed as to pathogenesis.

PMID- 9280647
TI  - [Admission to a hospital with a stroke: the situation at the present time].
AB  - OBJECTIVE: Patients with ictus spend a long time in hospital. This is partly to
      the fact that it is a severe condition. In which complications frequently
      develop, in elderly patients with social problems due to their subsequent
      disability. Also this prolonged hospital stay may be the result of misconceptions
      as to the object of hospitalization in cases of stroke. DEVELOPMENT: Whether to
      admit to hospital for stroke depends on the type of hospital, availability of
      other centres for chronic cara and the existence of satisfactory social services.
      During the acute phase of the illness, medical and neurological stability of the
      process is necessary together with minimization of cerebral damage. Hospital stay
      may be prolonged to study other secondary medical conditions and because of the
      uncertain prognosis using evolutionary criteria. This cases additional medical
      complications in these patients. Findings of the 'Grupo de Estudio de
      Enfermedades Cerebrovasculares de la SEN', show that prolonged hospital stay in
      cases of intracerebral haemorrhage cannot be justified by either the severity of
      the clinical picture, the mortality whilst in hospital or the functional capacity
      of the patient. CONCLUSION: The objectives of hospitalization in cases of ictus
      must be defined to optimize care, reduce complications and improve use of health
      care resources.

PMID- 9280646
TI  - [Subacute combined degeneration of the spinal cord: manifestations of esophageal
      epidermoid carcinoma].
AB  - INTRODUCTION: Subacute combined degeneration of the spinal cord associated with
      vitamin B12 deficit is well known. However a paraneoplastic induced
      cyanocobalamin malabsorption responsible for either subacute combined
      degeneration of the spinal cord, has not been reported. Moreover, the possibility
      of either subacute combined degeneration of the spinal cord may be manifestation
      of a cancer, it's unknown. CLINICAL CASE: We present the case of a 73-year-old
      woman with cutaneous paleness and clinical manifestations of a subacute combined
      degeneration of the spinal cord. Laboratory analysis showed a megaloblastic
      anemia and Schilling test showed cyanocobalamin malabsorption corrected by
      intrinsic factor. Anti-intrinsic factor antibodies were positive. Chronic
      atrophic gastritis and immunological diseases associated with pernicious anemia
      or with anti-intrinsic factor positive, were excluded. A hidden esophageal
      squamous cell carcinoma was discovered. Necropsy confirmed both, subacute
      combined degeneration of the spinal cord and esophageal carcinoma in the absence
      of chronic atrophic gastritis. CONCLUSIONS: Anti-intrinsic factor antibodies were
      the only found factor which could explain cyanocobalamin malabsorption. A
      esophageal squamous cel carcinoma was discovered. In our case, vitamin B12
      malabsorption had a paraneoplastic origin mediated by anti-intrinsic factor
      antibodies. Subacute combined degeneration of the spinal cord may be the
      manifestation of a hidden esophageal squamous cell carcinoma.

PMID- 9280648
TI  - [Is a transitory ischemic accident diagnosed during inpatient or outpatient
      care?].
AB  - Both transient ischemic attacks (AIT) and minor strokes are common clinical
      findings in cerebro-vascular disease. They are warnings of the presence of a high
      risk that a more serious ictus may subsequently occur and cause irreversible
      lesions. Although only 40% of all strokes are preceded by AIT, and a first ictus
      may itself be serious, there are now available effective methods of treatment
      which can reduce the risk of a serious ictus in patients who have had AIT. There
      is also a higher death rate and greater risk of ischaemic cardiopathy in these
      patients. Since this risk is higher during the first month, all patients with
      recent AIT should be treated as emergency cases. If delay in diagnosis and
      treatment of cerebro-vascular disease may be costly for both the patient and the
      health system, in AIT this is particularly so.

PMID- 9280649
TI  - [Is hospital admission urgent in stroke?].
AB  - OBJECTIVE: To review the evidence that strokes need urgent hospital admission.
      DEVELOPMENT: The need for urgent hospitalization varies with stroke type.
      Immediate hospital admission it is unquestionable for subarachnoid hemorrhage and
      probably also for intracerebral hemorrhages. An acute CT can disclose non
      vascular pathology, an hemorrhage or early infarct signs. Being examined by a
      neurologist within six hours from onset improves outcome. How early should a
      cardioembolic stroke be anticoagulated is still a matter of debate. Aspirin and
      nadroparine given within 48 hours improve acute ischemic stroke outcome. A 10%
      benefit on functional outcome was obtained by IV rtPA, given within three hours.
      The majority of acute stroke trial with neuroprotectors have a six hours windows
      design, but the percentage of patients arriving hospital within that interval is
      variable. CONCLUSION: Early hospital admission of acute stroke is beneficial. An
      educational effort is needed to increase early hospital referral of acute stroke
      patients.

PMID- 9280650
TI  - [Duration and objectives of hospital admission to stroke units].
AB  - OBJECTIVE: The epidemiological importance of Acute Cerebrovascular Disorders
      (ECVA) has led to a need for specific units to care for these patients. We review
      the effect of these units on Neurology Departments. Development. In the 1970s
      Stroke Intensive Care Units were created. In the 1980s these units were replaced
      by Non-intensive or Intermediate Care Units (Acute Stroke Units). These Acute
      Stroke Units are more efficient than the previous units and were found to reduce
      mortality, morbidity, hospital stay and costs. Care was complemented by specific
      Rehabilitation Units. The design we propose takes into consideration the
      integration of a Stroke Unit in the Neurology Department, in the Hospital and in
      the Health Area. After one year results were compared with those of the previous
      year, when a specific team cared for such patients. There was an 18.5% reduction
      in total hospital stay and a 23.5% reduction for ECVA patients, with a 21%
      increase in admissions. The number of complications was reduced by 40.91%.
      CONCLUSIONS: Stroke Units are extremely useful in Neurology Departments. They
      lead to reduced morbi-mortality, sequelae, average hospital stay and costs. The
      functional condition of the patients also improves.

PMID- 9280652
TI  - [Hospital stay after cerebral hemorrhage].
AB  - INTRODUCTION AND OBJECTIVES: Patients with intracerebral haemorrhage (ICH) make
      up 10-12% of the total number of patients admitted to hospital. In this paper we
      evaluate the period of time during which the maximum benefit is obtained by a
      patient with this type of ictus. DEVELOPMENT AND CONCLUSIONS: We therefore review
      the aetiology, physiopathological course and complications of HIC in order to
      better understand the circumstances which affect the average hospital stay and
      identify the factors which can be acted upon and when to do so. We conclude that
      the average hospital stay does not depend on the type of ictus, in the sense of
      whether it is ischaemic or haemorrhagic, but on its severity which mainly depends
      on the size of the lesion. We find no justification for a patient with ICH
      spending more time in hospital than one with an ischaemic ictus, except where it
      is suspected that a cerebral aneurysm is the cause of the haemorrhage.

PMID- 9280651
TI  - [Morbidity in hospital admission for stroke].
AB  - INTRODUCTION: In spite of advances in the prevention and treatment of ischemic
      vascular disease, this continues to be one of the main causes of disablement and
      prolonged hospitalization in developed countries. Also, hospitalization itself
      leads to complications which have a negative effect on the morbi-mortality of
      these patients during the time spent in hospital. OBJECTIVE: We decided to study
      the effect of systemic complications during the period of hospital stay, on the
      functional recovery of patients which ictusl. MATERIAL AND METHODS: A prospective
      study was made of 47 patients admitted to our unit for neurological deficit of
      more than 24 hours evolution and of cerebrovascular aetiology. Functional
      recovery was evaluated by means of the index of Barthel on discharge and after a
      period of 3 months with respect to the degree of neurological involvement
      (Canadian scale on admission), glycemia on admission, time spent in hospital and
      the occurrence of systemic complications in hospital. RESULTS: These were no
      differences between the groups of patients with and without systemic
      complications regarding age, glycemia and Canadian scale on admission. Nor wes
      there any difference between the groups regarding the number of patients with
      significant deterioration of their neurological condition (decrease > 20% in the
      EC). Functional recovery on hospital discharge was worse in the group with
      systemic complications (IB: 43.05 +/- 34.1: as compared with IB: 72.8 +/- 22.7 in
      the group without complications). This difference persisted after 3 months.
      CONCLUSIONS: Systemic complications related to hospitalization have a negative
      effect on the functional recovery of patient with ictus and also prolong the time
      spent in hospital.

PMID- 9280653
TI  - [Admission to hospital versus home care for stroke].
AB  - The incidence and prevalence of cerebrovascular disease is very high. This is a
      major sanitary problem. There are no studies comparing the management of acute
      stroke as inpatient or outpatient, publications about each of these items are
      analyzed. General Practitioners may play a very important role, not only at the
      first step in the attention of stroke patients. Admission criteria for stroke and
      hospitalization span for its different ethiopathogenic types are revised.

PMID- 9280654
TI  - [The effect of clinical trials on hospital admission for stroke].
AB  - OBJECTIVE: To analyze the contribution of clinical trials in the hospital
      treatment of acute ischaemic cerebrovascular disease. DEVELOPMENT: In recent
      studies many trials have been designed for the treatment of the acute phase of
      this illness. Based on experimental studies, the drugs used in the trial need to
      be given within a 'therapeutic window' of less than six hours from the onset of
      the illness. This time factor has led to a radical change in the organization of
      hospital services dealing with this illness. In order to run clinical trials the
      medical staff have had to be organized into functional stroke units for the swift
      protocolized diagnosis of the condition. Also information has to be given to
      health workers regarding the need for urgent specialized treatment. Several
      studies have shown that early, specialist treatment reduces morbi-mortality, time
      spent in hospital and financial cost in these patients. CONCLUSION: Clinical
      trials in acute cerebrovascular pathology have formed the basis for the creation
      of stroke units, led to the drawing up of protocols for the diagnosis and
      guidelines for treatment. It has also made the medical profession more aware of
      the importance of early diagnosis and specialized treatment in acute cerebral
      ischaemia.

PMID- 9280655
TI  - [Admission to hospital for subarachnoid hemorrhage].

PMID- 9280656
TI  - [Long or short hospital stay in cerebral vascular diseases].

PMID- 9280657
TI  - [Duration and objectives of admission to hospital with a cerebral infarct].

PMID- 9280659
TI  - [Preventive medicine for the aged].

PMID- 9280658
TI  - [Individualization of retrograde amnesias. On the basis of autobiographical and
      semantic forms].

PMID- 9280660
TI  - [Clinical and molecular pathology in brain aging].

PMID- 9280661
TI  - [Cerebral vascular pathology in aging].

PMID- 9280662
TI  - [In vitro and in vivo techniques for the location of the receptors in human
      brain: methodological basis and general applications].

PMID- 9280663
TI  - [Receptors localization in human brain: contribution to neurochemistry of normal
      aging and neurodegenerative diseases].

PMID- 9280664
TI  - [Motor disorders of vascular origin in aged people].

PMID- 9280665
TI  - [Drug-related motor disorders in aged people].

PMID- 9280666
TI  - [Epidemiology of dementias].

PMID- 9280667
TI  - [Molecular mechanisms in Alzheimer's disease].

PMID- 9280668
TI  - [Dementias by prions: a new pathogenic paradigm].

PMID- 9280669
TI  - [Pharmacotherapeutical perspectives in Alzheimer's disease].

PMID- 9280670
TI  - [Introduction: cerebral diseases in aging].

PMID- 9280671
TI  - [Tacrine in Alzheimer's disease].

PMID- 9280672
TI  - [Epidemiology of drugs intake in aged people].

PMID- 9280673
TI  - The pharmaceutical industry faced with the double challenge of aging.

PMID- 9280674
TI  - [The impact of pharmaceutical expenses].

PMID- 9280675
TI  - [Demographic perspectives of Communidad Autonoma Vasca and the OCDE's countries].

PMID- 9280676
TI  - [Morphological and neurochemical dysfunctions in normal cerebral aging].

PMID- 9280677
TI  - [Political urban and architectonic reflections suitable to new population
      setting].

PMID- 9280678
TI  - [Functional anatomy of the basal ganglia].
AB  - Basal ganglia comprises several subcortical nuclei which have different
      neurochemical and physiological characteristics. This article reviews the actual
      knowledge about the anatomy and physiology of the basal ganglia as well as its
      role in motor control.

PMID- 9280679
TI  - [Dopaminergic system and neuronal death].
AB  - The mechanism involved in dopaminergic neuronal death remains unknown. Increased
      oxidative stress, inhibition of mitochondrial respiratory chain and apoptosis
      have been suggested as possible factors mediating cellular death. This article
      reviews the most important findings reported in parkinsonian brains related to
      nigral neuronal death.

PMID- 9280680
TI  - [Neurochemistry of Parkinson's disease and parkinsonism plus].
AB  - The neurochemistry of Parkinson's disease and other degenerative parkinsonisms is
      reviewed, emphasizing the changes described in the dopaminergic system.
      Presynaptic dopaminergic markers are reduced over the striatum in all these
      degenerative parkinsonisms, dopamine receptor changes being more heterogeneous.
      While in Parkinson's disease D1 and D2 receptors remain preserved as compared to
      controls, in progressive supranuclear palsy there is a loss of nigral D1
      receptors and of striatal D2 receptors. This finding has also been described in
      striatonigral degeneration. There are no clear data about the status of D3, D4
      and D5 dopamine receptors in these conditions. The alterations in other
      neurotransmission systems, cholinegic, adrenergic, serotoninergic and peptidergic
      are, in general, less dramatic, although they have not been studied in detail. To
      conclude, further studies are necessary in these field, in these moment, however,
      the preservation of striatal D2 dopamine receptors is the neurochemical finding
      with the best correlation with the response to levodopa or other dopaminergic
      agonists.

PMID- 9280681
TI  - [PET and SPECT in Parkinson's disease].
AB  - Positron emission tomography (PET) with [18F] fluorodopa (FD) assesses
      nigrostriatal function in vivo. Measurements deriving from FD PET have direct
      lineal relationship to the nigral cell count in normal ageing and in Parkinson's
      disease (PD), although in PD the progression of the decline in nigrostriatal
      dopaminergic function is faster than the controls. The functional anatomy of the
      movements has been studied using PET and SPECT. The supplementary motor area
      (SMA) dysfunction is responsible for bradykinesia in Parkinson. The SMA is
      undereactive in PD during self-generated movements, and this underactivation is
      reversed by the administration of apomorphine and modulate by the stereotaxic
      ventral pallidotomy. PET has been used, also, to attempt the differentiation of
      PD, multiple system atrophy (MSA) and PSP, in vivo, using a number of different
      radioligands (opiod, dopamine receptor binding). [11C] raclopride PET and [123I]
      IBF SPECT seemed a promising agents to assessing D2 receptor status in humans.
      Studies of D2 status have demonstrated normal or increased D2 receptor density in
      PD and decreased receptor density in PSP and MSA. Using SPECT has been
      demonstrated marked differences of the DA transporters located on dopaminergic
      terminals in the striatum in healthy controls and PD patients. Also the
      correlation of SPECT measures of transporters of DA and motor severity suggests
      that this may be a useful marker of disease severity in PD.

PMID- 9280682
TI  - [Physiopathology of the dyskinesias induced by L-dopa].
AB  - Dyskinesias are one of most frequent motor complications of parkinsonian patients
      on chronic levodopa treatment. This article reviews their clinical
      characteristics, risk factors, pathophysiology and possible therapeutical
      approaches.

PMID- 9280683
TI  - [Psychiatric complications of L-dopa: physiopathology and treatment].
AB  - This review article deals with the psychiatric complications of L-dopa in
      Parkinson's disease. There is a 20% incidence of these complications with
      estimations varying in the different publications between 10% and 50%. They
      usually occur after several years of treatment. The complications are varieds and
      include anxiety states, affective disorders, psychoses, disorders of recognition
      and other mental disorders. They may be explained in physio-pathological terms as
      an alteration of the dopaminergic system of the mesolimbic and mesocortical
      circuits. Treatment should be adjusted individually. In most cases the dosage of
      levodopa should be lowered or stopped altogether. In other patients treatment
      with benzodiazepines, neuroleptic antidepressants and even electric shock
      treatment may be necessary.

PMID- 9280684
TI  - [Initial treatment of Parkinson's disease].
AB  - The initial treatment of Parkinson's disease should be addressed to improve
      symptoms, slow down the progression of the illness and avoid long and short term
      complications. Drugs currently available for symptomatic treatment are levodopa,
      dopaminergic agonists, anticholinergics and amantadine. Levodopa is still the
      goldstandard. Both the standard preparations of carbidopa/levodopa or
      benserazide/levodopa and the slow release preparations are suitable for initial
      treatment. However, when to start levodopa remains controversial. Dopaminergic
      agonists are useful symptomatic drugs. They can be used in monotherapy, but
      usually require the addition of levodopa to obtain a satisfactory long term
      therapeutic response. Used as adjuvant treatment to levodopa, they help lowering
      the dosage of levodopa. Anticholinergic drugs effectively improve symptoms such
      as tremor and rigidity but their use is limited by their side effects,
      particularly in older people. Amantadine may be a useful drug for initial
      treatment of Parkinson's disease when symptoms are not severe. Symptomatic
      treatment should be considered individually in each patient. If there is only
      slight disability, treatment may be started with amantadine alone or with a
      dopaminergic agonist. If there is greater disability, levodopa or the
      simultaneous use of levodopa and a dopaminergic agonist should be considered.
      Anticholinergic drugs should be reserved for young patients with tremor as the
      main symptom. The newer dopamine agonists and inhibitors of catachol-o
      methyltransferase (COMT) are coming therapeutic options. Selegiline, a MAOB
      inhibitor with a possible neuroprotective effect, should also be considered as
      initial option for Parkinson's disease.

PMID- 9280686
TI  - [Surgical therapy of Parkinson's disease].
AB  - The high incidence of motor and psychiatric complications in patients on chronic
      levodopa treatment has lend to the renaissance of the surgery for the treatment
      of Parkinson's disease. The globus pallidus medialis (GPM) and the thalamic Vim
      constitute the main surgical targets. At present, their acute location is
      guaranteed by the development of new neuronal recording systems. Other
      therapeutical approaches include Vim electrical stimulation for parkinsonian
      patients with tremor. Chronic electrical stimulation of GPM and subthalamic
      nucleus (STN) are under evaluation, but preliminary results suggest that this
      treatment could be of great value in the treatment of patients with Parkinson's
      disease.

PMID- 9280685
TI  - [Pharmacological therapy of complicated Parkinson's disease].
AB  - The progression of Parkinson's disease, and the increase in the time under
      therapy with levodopa of this disease, leds to development of several
      complications, including loss of efficacy of the therapy, motor fluctuations,
      dyskinesias, psychiatric disorders, etc. These complications cause serious
      limitations to the management of the advanced disease. This article reviews the
      current status of the therapeutic approaches to the management of complicated
      Parkinson's disease.

PMID- 9280687
TI  - [Neuroprotective and neurorestorative therapy in Parkinson's disease].
AB  - It has been suggested a possible role of oxidative stress, neuromelanin,
      mitochondrial dysfunction, calcium-binding protein deficiency, nitric oxide,
      trophic factors deficiency, and cytokines, in the pathogenesis of Parkinson's
      disease. Based on these mechanisms it might be established neuroprotective
      therapies but, up to date, the results reported are inconsistent. Many
      experimental data suggest the usefulness of some restorative therapy, such as
      neural grafts, genic therapies, etc. This article reviews the current knowledge
      on the possible neuroprotective and restorative treatments in Parkinson's
      disease.

PMID- 9280688
TI  - [Which objective of triglyceridemia should be researched during treatment of non
      insulin-dependent diabetes?].

PMID- 9280689
TI  - The challenges ahead.

PMID- 9280690
TI  - International Congress VIII on Endovascular Interventions. Scottsdale, Arizona,
      February 12-16, 1995. Abstracts.

PMID- 9280691
TI  - Circulatory Biomechanics and Cardiovascular Pathologies. Marseille, France, July
      7-8, 1995. Abstracts.

PMID- 9280693
TI  - Recent literature on cell stress & chaperones.

PMID- 9280692
TI  - Vascular aneurysms: a side-splitting affair.

PMID- 9280694
TI  - [The extent of diastolic dysfunction and its correlation with subjective
      impairment of physical capacity in dilated cardiomyopathy].
AB  - OBJECTIVE: To find out whether in patients with dilated cardiomyopathy (DCM)
      there is a correlation between subjective reduction in physical capacity and the
      transmitral Doppler profile as a measure of left ventricular (LV) filling.
      PATIENTS AND METHODS: 30 consecutive patients (24 men, six women; average age 55
      +/- 2 years) with chronic primary DCM were examined by Doppler echocardiography
      to determine possible differences in LV filling pattern, in correlation with
      subjective impairment of physical capacity graded according to the New York Heart
      Association (NYHA) classification. RESULTS: Mean LV ejection fraction was 34 +/-
      1%. All patients were in sinus rhythm. Eight patients, in NYHA class I had nearly
      normal LV filling (E wave 79 m/s, A wave 0.76 m/s); 11 patients in class II had
      impaired relaxation (E wave 0.77 m/s. A wave 0.82 m/s) and 11 in class III/V had
      a restricted filling pattern (E wave 0.98 m/s. A wave 0.57 m/s). There was a
      significant difference between class II and class III/IV patients with regard to
      E wave deceleration time (0.15 and 0.11 s, respectively; P < 0.05), as well as
      between class I and class III/IV patients (0.18 and 0.11 s, respectively; P <
      0.05). The A wave deceleration time was clearly shorter in class III/IV than
      class II (0.08 s and 0.11 s; P < 0.05) and class I patients (0.08 s and 0.10 s; P
      < 0.05). CONCLUSIONS: The extent of LV diastolic dysfunction correlated with
      subjective physical capacity. The more the LV filling pattern had changed from
      normal towards restricted, the greater the patient's symptoms.

PMID- 9280695
TI  - [Nail polish allergy. An important differential diagnosis in contact dermatitis].
AB  - HISTORY AND CLINICAL FINDINGS: Case 1. A 34-year-old woman presented with a
      recurrent, itching and erythematous plaque on her right cheek. Case 2. A 27-year
      old woman reported itching erythema on her fingertips from time to time recently.
      Inspection revealed dyshidrosiform blisters. Both patients had been using nail
      varnish and varnish remover. Case 3. A 49-year-old woman had, for about 5 years,
      repeatedly experienced itching erythema at the perionychium of several fingers on
      which she had placed artificial nails. Marked oedema and erythema was noted.
      INVESTIGATION: Extensive epicutaneous tests were performed on these patients.
      They showed sensitisation against important allergens in nail varnish
      (toluolsulphonamide-formaldehyde resin), nail varnish remover (benzophenone-2)
      and artificial nails (ethylacrylate), respectively. The three patients also
      showed type IV sensitisation against other substances. DIAGNOSIS, TREATMENT AND
      COURSE: Epicutaneous tests documented type IV allergies to important constituents
      of nail varnish, nail varnish remover and artificial nails. Symptoms and skin
      changes disappeared when these three items were no longer used. CONCLUSION:
      Allergies against nail varnish and its remover and against artificial nails
      should be included in the differential diagnosis of skin allergies, even when
      patients have additional type IV sensitizations against common allergens. As the
      causative allergen can be easily avoided, knowledge of the particular problems
      associated with these allergies is of a great practical significance.

PMID- 9280696
TI  - [The Churg-Strauss syndrome with cerebral seizures and terminal kidney failure].
AB  - HISTORY AND CLINICAL FINDINGS: A 67-year-old man with known bronchial asthma was
      admitted to hospital because of deteriorating general state of health, fever,
      progressive renal failure and confusional states. INVESTIGATIONS: Erythrocyte
      sedimentation rate was 70/95 mm and the concentration of C-reactive protein
      raised to 30 mg/dl. WBC count was 19,000/microliter with 39% eosinophilia.
      Anticytoplasmatic antibodies (cANCA) had a high titre (1:160). On admission the
      creatinine level was 5.6 mg/dl. Renal biopsy indicated marked glomerular and
      tubulo-interstitial scarring. Chest radiograms showed transient pulmonary
      infiltrates. Churg-Strauss syndrome (CSS) was diagnosed on the basis of the
      clinical and biochemical findings. TREATMENT AND COURSE: Haemodialysis was
      instituted to counteract the renal failure with water retention. Inflammatory
      parameters and clinical symptoms rapidly responded to administration of
      corticosteroids (prednisolone, initially 250 mg/d for 3 days, then 150 mg/d for 5
      days followed by slowly decreasing doses). Two weeks after starting prednisolone
      he had secondary generalised seizures. Magnetic resonance imaging (MRI) of the
      skull demonstrated marked hyperintense focal changes which in their pattern were
      characteristic of cerebral vasculitis. As a steroid-refractory condition had to
      be assumed, cyclophosphamide was also given (100 mg/d). Within 6 weeks the
      clinical symptoms gradually regressed and the MRI changes became practically
      normal. CONCLUSION: Early combined immunotherapy should be given if CSS runs a
      complicated course, rather than the usually recommended corticosteroid
      monotherapy.

PMID- 9280697
TI  - [Diagnostic criteria for the indication of growth hormone substitution in adults.
      The Hypophysis and Hypophyseal Tumor Working Group of the German Society for
      Endocrinology].

PMID- 9280699
TI  - [Explanation and agreement (informed consent) in clinical practice].

PMID- 9280698
TI  - [Antimicrobial therapy in neutropenia].

PMID- 9280700
TI  - [The enlistment of the owners of a day clinic in medical emergency service. The
      judgement of the Federal Social Court of 18 October 1995].

PMID- 9280701
TI  - [Pancreatic elastase 1 in the stool].

PMID- 9280702
TI  - [The therapy of systemic lupus erythematosus].

PMID- 9280703
TI  - [The advantages of protease inhibitors in the battle against HIV].

PMID- 9280704
TI  - [Epidemiological and prognostic data from 2054 patients of an internal medicine
      intensive care unit].
AB  - BACKGROUND: Computer-based data collection and objective gathering of degree of
      illness severity and risk of death with a prognostic scoring system make it
      possible to obtain, in addition to epidemiological and aetiological data, risk
      related outcome values for patients in an intensive care unit. PATIENTS AND
      METHODS: All 2054 patients who during a 2-year period (1995-1996) had stayed in a
      medical intensive care unit (MICU) for more than 4 hours were studied
      prospectively. The simplified acute physiology score II (SAPS II), risk of death,
      duration of stay in the MICU and in the hospital, and death rates during MICU and
      hospital stay were determined. Mean and median values and histograms of the
      various parameters as well as the standardized mortality index (SMI: observed/
      predicted death rate with 99% confidence limits) were calculated for each of the
      patients and certain defined subgroups (basic disease, age, risk). Receiver
      operating characteristics curves (discrimination) and calibration curves were
      obtained for SAPS II. RESULTS: Mean age for the cohort was 59.8 years, duration
      of stay in the MICU 3.1 days, in hospital 14.7 days, SAPS II was 30.3 points,
      death risk 0.17, death rate during ICU stay was 8.3%, during hospital stay 13.9%
      and the SMI 0.8% (0.74-0.88). Cardiac disease was the most common underlying
      condition (60%), while the small group of neurological conditions was remarkable
      for the high degree of severity and unfavourable prognosis. Both death rate and
      degree of disease severity increased with age. But the SMI was not significantly
      higher than 1.0 in both the elderly patients and the high-risk group of patients
      (on ventilator, renal replacement procedures, death risk > 0.5). CONCLUSIONS:
      Most patients in a MICU have underlying cardiac disease. Permanently available
      neurological consultation is essential. The high hospital death rate for elderly
      patients and those requiring respiratory support is a problem of disease
      severity, not of the quality of treatment. The risk of death is high on transfer
      to a general ward. Determination of the SMI is recommended for internal quality
      control in an ICU.

PMID- 9280705
TI  - [Stenosis of the terminal ileum. Endometriosis as the differential diagnosis of
      Crohn's disease].
AB  - HISTORY AND CLINICAL FINDINGS: A 25-year-old woman had for 5 years complained of
      lower and mid-abdominal pain, at first monthly but later continuous and gradually
      increasing in severity. At the same time she had diarrhoea associated with
      nausea, vomiting and weight loss. Physical examination showed a markedly
      distended abdomen, diffuse pain on pressure over the whole abdomen, most marked
      in the left middle and lower part, and high pitched peristalsis, but was
      otherwise unremarkable. INVESTIGATIONS: Abdominal radiography indicated small
      intestinal ileus, while ultrasound revealed absent peristalsis in the small
      intestine and a 10 cm stenosis in the terminal ileum. Coloscopy demonstrated a
      fibrosed stenosis of the terminal ileum but a biopsy showed no specific changes.
      TREATMENT AND COURSE: Under suspicion of Crohn's disease with stenosis of the
      terminal ileum a partial resection of the ileum was performed. The ileum was on
      inspection thickened with scar tissue but no inflammation. Histology revealed
      florid chronic mucosal and submucosal inflammation, haemorrhages and ulcers, as
      well as numerous islands of endometriosis in the subserosa and muscularis
      propria. CONCLUSION: Endometriosis is a rare disease in women of the reproductive
      age, but should be considered in the differential diagnosis of Crohn's disease of
      the terminal ileum.

PMID- 9280706
TI  - [Bradycardiac atrial fibrillation after consuming herbal tea].
AB  - HISTORY AND CLINICAL FINDINGS: One day after drinking what she thought to be a
      tea made from borage leaves a 72-year-old woman developed nausea, vomiting and
      diarrhoea, later also flickering in her eyes and palpitations. She was in a good
      general state with a blood pressure of 120/75 mm Hg and an irregular heart rate
      of 52/min. Physical examination was otherwise unremarkable. She had not been on
      any medication. INVESTIGATIONS: The usual laboratory tests were normal. The
      electrocardiogram showed atrial fibrillation with a slow ventricular rate with
      pauses of up to 1.5s. intermittently type I and II 2 degrees AV block, and
      depressed concave ST segments. The level of digoxin was 3.93 ng/ml, that of
      digitoxin 133.5 ng/ml. TREATMENT AND COURSE: The patient's symptoms quickly
      improved under symptomatic treatment. Further questioning suggested that she had
      probably mistaken foxglove leaves for those of borage when picking them to make a
      brew. CONCLUSION: If cardiac arrhythmias have occurred after intake of self
      picked herbal leaves one should consider digitalis intoxication resulting from
      misidentification.

PMID- 9280707
TI  - [The diagnosis and therapy of familial adenomatous polyposis coli].

PMID- 9280708
TI  - [The effective therapy of the hot flashes during hormone withdrawal treatment in
      patients with advanced prostatic carcinoma].

PMID- 9280709
TI  - [An additional 10% tax in the hospital area for head physicians with old
      contracts. The judgement of the Federal Labor Court of 22 January 1997].

PMID- 9280710
TI  - [The value of the lymphocyte transformation test (LTT) in allergological
      diagnosis].

PMID- 9280711
TI  - [Hypothyroidism and creatine kinase].

PMID- 9280712
TI  - [Latex allergy].

PMID- 9280713
TI  - [Immune protection and injury after viral infection].

PMID- 9280714
TI  - [Renal hemodynamics and proteinuria in chronic glomerulonephritis treated with
      beta-receptor blockers or ace inhibitors].
AB  - BACKGROUND AND OBJECTIVE: In patients with chronic glomerular nephropathy
      associated arterial hypertension and proteinuria are considered to be cardinal
      risk factors in the progressive deterioration of renal function. Treatment
      regimens which reduce proteinuria and hypertension improve prognosis. The effect
      of the new beta-receptor blockers compared to common ACE-Inhibitors is of special
      interest. PATIENTS AND METHODS: The studied cohort consisted of 11 patients with
      CGN, hypertension and proteinuria > 400 mg/24 h. Four drugs were given for 4
      weeks, doubly blinded and randomized according to a "Latin-square design":
      Celiprolol (beta-1-antagonist, beta-2-agonist, 200 mg/d), Atenolol (selective
      beta-1-antagonist, 50 mg/d), Ramipril (ACE-inhibitor, 2.5 mg/d) and placebo.
      There was a two-week wash-out phase between each of the four treatment phases. At
      the end of each treatment phase glomerular filtration rate (GFR) and effective
      renal plasma flow (ERPF) were measured by inulin and para-amino-hippuric acid
      (PAH) clearance. Proteinuria was determined in the course of a three-day
      collection period at the end of each treatment phase. During this period blood
      pressures were measured with a continuous 24-hour blood pressure monitor.
      RESULTS: Mean arterial blood pressure (MAP) was significantly reduced, compared
      with placebo, by all three antihypertensives (108 +/- 9 mm Hg with placebo, 98 +/
      12 mg Hg with atenolol, 101 +/- 11 mm Hg with celiprolol and 98 +/- 8 mm Hg with
      ramipril; P < 0.01). Celiprolol produced a significant rise In ERPF (322 +/- 109
      ml/min with placebo, 391 +/- 110 ml/min with celiprolol: P < 0.05). GFR was
      slightly, but not significantly, reduced by celiprolol and atenolol. Filtration
      fraction remained unchanged with atenolol and celiprolol, while it was slightly,
      but not significantly, reduced with ramipril. Compared with the placebo, all
      three drugs significantly reduced proteinuria (P < 0.05): 1.8 +/- 1.3 g/24 h with
      placebo, 1.2 +/- 1.2 g/24 h with atenolol, 1.2 +/- 1.1 g/24 h with celiprolol and
      1.4 +/- 1.4 g/24 h with ramipril. CONCLUSION: These data indicate that, in
      addition to ACE inhibitors, the new generation of beta-receptor blockers in
      particular, because of their vasodilator action, favourably influence proteinuria
      and renal blood flow in patients with CGN and arterial hypertension.

PMID- 9280715
TI  - [Secondary resistance to coumarin derivatives in a patient with a
      hypercoagulability syndrome].
AB  - HISTORY AND CLINICAL FINDINGS: A 23-year-old woman with deep (leg) vein
      thrombosis was hospitalised because the Quick value had not decreased despite
      administration of phenprocoumon. Two years previously she had sustained an
      anterior wall myocardial infarction and a scar on her right kidney had been an
      incidental sonographic finding. There was bluish, fine reticular discoloration
      over the toes of both legs. Physical examination was otherwise unremarkable
      except for obesity. INVESTIGATIONS: The concentration of creatine kinase was
      raised to 250 U/l and that of lactate dehydrogenase to 300 U/l. The platelet
      count was decreased to 75/nl. The level of IgG anti-cardiolipin antibodies was
      raised (204 U/l) and the test for lupus anticoagulant positive. A biopsy of the
      skin from a toe revealing livedoid vasculitis, primary antiphospholipid syndrome
      (PAPS) was diagnosed. TREATMENT AND COURSE: Noncompliance, excessive vitamin K
      ingestion, drug interaction and malabsorption were excluded as cause of the
      lacking action of phenprocoumon. Despite anti-coagulation with high-dosage low
      molecular heparin and inhibition of platelet aggregation with ticlopidine and
      finally also immunosuppressive treatment with cyclophosphamide, skin necroses
      developed on the toes and she had recurrent pulmonary embolisms of which she
      died. CONCLUSION: Standard treatment of PAPS is effective anti-coagulation with
      coumarin derivatives. Secondary resistance to coumarin is a rare occurrence: its
      cause remains unknown.

PMID- 9280716
TI  - [Successful lysis of iliofemoral and inferior vena cava thrombi in heparin
      induced type-II thrombocytopenia].
AB  - HISTORY AND CLINICAL FINDINGS: After 10 days of intravenous heparin treatment of
      a 25-year-old woman with recurrent pulmonary emboli, thrombocytopenia occurred
      with a platelet drop from 1.52 x 10(5)/microliter to 3.6 x 10(4)/microliter.
      Heparin-induced platelet activation assays confirmed the diagnosis of heparin
      induced thrombocytopenia (HIT). The detected heparin-dependent antibodies
      exhibited in vitro cross-reactivity with low-molecular-weight heparins, but not
      with danaparoid. TREATMENT AND COURSE: After heparin was stopped and platelet
      counts were normal, a massive thrombosis of the iliofemoral veins and the
      inferior vena cava occurred. Under protection of a temporary vena cava filter,
      systemic anticoagulation with danaparoid (anti-factor Xa-activity 0.4-0.8 U/ml)
      and transcatheter thrombolysis with urokinase (70,000 U/h) was initiated. Within
      8 days of treatment a complete recanalisation of the occluded iliofemoral and
      caval veins was achieved. Oral anticoagulation with phenprocoumon was started and
      the patient has since then been free of symptoms. CONCLUSION: The case
      demonstrates successful treatment of massive iliofemoral and caval thrombosis in
      the HIT syndrome achieved by combined transcatheter administration of urokinase
      and systemic infusion of danaparoid.

PMID- 9280717
TI  - [Diagnosis and therapy of chlamydia infections].

PMID- 9280718
TI  - [Stomach cancer and MALT lymphoma: prevention with Helicobacter pylori
      eradication].

PMID- 9280719
TI  - [Hypercalcemia].

PMID- 9280720
TI  - [Minimally invasive therapy for gallbladder stones].

PMID- 9280721
TI  - [Stomach wall necrosis after endoscopic sclerotherapy].

PMID- 9280722
TI  - Ribozyme-mediated cleavage of the MDR-1 transcript restores chemosensitivity in
      previously resistant cancer cells.

PMID- 9280723
TI  - [Repair in rheumatic mitral valve insufficiency].
AB  - OBJECTIVES: Emerging evidence indicates that etiology plays an essential role in
      the results of mitral valve repair. In this study, we examined the long-term
      performance of this procedure in 61 consecutive patients with pure rheumatic
      mitral insufficiency. PATIENTS: Patient ages ranged from 4 to 74 years (mean:
      51.7 +/- 16). Preoperatively, 94% of the patients were in NYHA class II or III.
      RESULTS: There was no hospital mortality. According to actuarial methods 94.1% of
      the patients were alive 7 years postoperatively and 83.3% were reoperation free.
      Freedom from reoperation was significantly higher in patients who received a
      prosthetic ring than in those who had other types of annuloplasty (96.7% vs
      59.3%; p = 0.001). As opposed to the literature, in our series there was no
      relationship between valve failure and age at the time of reoperation. There were
      only two cases of thromboembolism and one of infective endocarditis. CONCLUSIONS:
      This study confirms that mitral valve reconstruction in rheumatic valve
      insufficiency can yield satisfactory long-term clinical results, although they
      are less than optimum compared with those obtained in patients with degenerative
      disease. Favourable results depend on routine use of a prosthetic ring as well as
      adequate patient selection. Attention should be focused on improved detection and
      suppression of rheumatic activity at the time of operation.

PMID- 9280724
TI  - [Differences in pharmacologic treatment after acute myocardial infarction. The
      role of treatment effectiveness].
AB  - BACKGROUND: Despite growing interest concerning the prescription of different
      drugs in different clinical settings, no explanatory variables have been
      determined. The aim of this study was to verify if there are any differences in
      drug prescription at the time of hospital release following myocardial infarction
      and if any of these differences can be explained by scientific evidence
      concerning treatment efficacy. METHODS: All drugs prescribed to 430 patients
      discharged from three different cardiology departments after acute myocardial
      infarction were analyzed. Based on current scientific evidence, it has been,
      ascertained that aspirin, beta-blockers and ACE-inhibitors can be prescribed
      unless contraindicate whereas anticoagulants, nitrates and calcium antagonists
      should be prescribed only in specific clinical conditions. The odd ratio of
      prescription of each drug among the three cardiology departments was calculated
      and adjusted for any clinical and test result variables that can specifically
      affect drug prescription. RESULTS: Different clinical characteristics of the
      patients discharged from the three cardiology departments are the following: mean
      age ranges from 60 to 66 years (p < 0.001), the incidence of non-Q myocardial
      infarction ranges from 23 to 45% (p < 0.001), post infarction angina ranges from
      6 to 15% (p = 0.016), left ventricular failure ranges from 6 to 13% (p = 0.003)
      and arrhythmia ranges from 5 to 18% (p = 0.007). The adjusted odd ratio for
      clinical and test results variables showed that prescriptions were similar for
      ACE-inhibitors (odd ratio 1.3; 95% confidence interval from 0.6 to 3.2), aspirin
      (OR 2.2; 95% confidence interval from 0.8 to 5.5), beta-blockers (OR 2.2, 95%
      confidence interval from 0.9 to 5.5) and oral anticoagulants (1.6; 95% confidence
      interval from 0.6 to 4.5). Instead, there is a statistically significant
      difference in the prescription of nitrates (OR 4.4; 95% confidence interval from
      1.6 to 12.3) and of calcium antagonists (OR 5.4%, 95% confidence interval from
      1.0 to 12.5). CONCLUSIONS: Evidence based drug efficacy after acute myocardial
      infarction seems to establish a uniform pattern of drug prescription in different
      cardiology departments.

PMID- 9280726
TI  - [Long-term follow-up on ventricular pre-excitation in pediatric age].
AB  - AIM: Little is known yet about the clinical aspects of ventricular pre-excitation
      in pediatric age. In order to define clinical course, assess the risk of
      malignant arrhythmia and evaluate indications for ablative therapy, we studied 82
      consecutive pediatric patients (pts) with this affection (61 males-21 females;
      mean age at diagnosis 5.1 years, range 1 day-15 years). RESULTS: Mean follow-up
      time was 66 months (range 3-252). Fifty-six pts (68.3%) were asymptomatic. One
      patient, who was affected with hypertrophic cardiomyopathy and died suddenly when
      she was 2 while her cardiac rhythm was being monitored, had an EKG pattern of
      asystolia. In 28 pts (19 m - 9 f, 34.1%), episodes of reentrant atrio-ventricular
      tachycardia, ranging from 160 to 320 beats/minute, were documented. Five pts,
      four of whom were less than 1 year old, had syncope or cardiac failure due to
      tachyarrhythmia. As far as maximum incidence of symptoms is concerned, two peaks
      were observed: within the first year and between 14 and 16 years of age. A
      transesophageal electrophysiologic study was performed in 22 pts,
      tachyarrhythmias were induced in 15, and risk criteria were satisfied in 3/22
      (13.6%). Five pts underwent catheter ablation of an accessory pathway and this
      was successful in three of them. CONCLUSIONS: The clinical course in this series
      of patients has been benign. Nevertheless, during the first year of life cardiac
      failure or syncope may occur because of high heart rates. The transesophageal
      electrophysiologic study, which is also easy to perform in pediatric patients,
      has been sensitive in assessing the risk of malignant arrhythmia, but it shows
      low predictive accuracy. Lastly, ablative therapy has shown lower efficacy in
      children than in adult patients.

PMID- 9280725
TI  - [The Registry for Angioplasty in Infarction (RAI): brief preliminary report on
      the main indicators and process of acute outcome].
AB  - BACKGROUND: Emergency coronary angioplasty can be the treatment of choice in
      selected patients with acute myocardial infarction in centers with adequate
      facilities and organization. METHODS: A multicenter observational study in
      patients with high-risk acute myocardial infarction was conducted to evaluate the
      quality of emergency angioplasty treatment according to process, acute and long
      term outcome, and use of resources. RESULTS: The RAI registry included 345
      patients with high-risk acute myocardial infarction who were admitted to six
      participating centers over a thirteen-month period. Emergency coronary
      angiography was performed in 261 patients (76%) and was followed by immediate
      angioplasty in 236 of them (68%). Mean door-to-procedure time was 58 +/- 47 min.
      Severe left ventricular failure was present at admission in 35 (13%) of the 261
      patients with emergency coronary angiography; and 29 of them were in cardiogenic
      shock (11%). Overall, in-hospital mortality for patients with angioplasty was
      7.6%; i.e., 43% and 3.7% for patients with and without shock, respectively.
      CONCLUSIONS: Despite logistical limitation, in centers with emergency angioplasty
      programs this treatment can be performed with favorable process and acute outcome
      characteristics in patients with high-risk myocardial infarction.

PMID- 9280727
TI  - [Differential types of pulmonary flow in bidirectional cavo-pulmonary anastomosis
      with an additional flow source].
AB  - While Fontan operation is considered a palliative procedure for the treatment of
      complex congenital heart disease, its morbidity and mortality are certainly not
      negligible, especially in high-risk patients. In our opinion, a bidirectional
      cavo-pulmonary anastomosis with an additional source of blood flow to the lungs
      (Blalock-Taussig shunt, pulmonary artery banding, native pulmonary stenosis)
      represents a valuable surgical option in this subset of patients. From November
      1992 to September 1994, sixteen patients with complex congenital heart disease
      underwent bidirectional cavo-pulmonary anastomosis, leaving an additional source
      of blood flow in place (modified Blalock-Taussig shunt in 9 cases, pulmonary
      artery banding in 6 cases, native pulmonary stenosis in 1 case). Eight of these
      patients (50%) were reinvestigated after a mean follow-up of 15.7 months (range 1
      26 m). It has been possible to differentiate two types of pulmonary blood flow,
      according to the nature of the additional flow source; in the case of cavo
      pulmonary anastomosis and pulmonary artery banding or pulmonary stenosis,
      pulmonary blood flow was pulsatile and evenly distributed to both lungs, while in
      the case of bidirectional cavo-pulmonary anastomosis and Blalock-Taussig shunt,
      pulmonary flow was non pulsatile and asymmetric (angiographic criteria). There
      were no hospital deaths. Late mortality was 12.5% (2 pts) due to worsening of
      atrioventricular valve regurgitation. In one of these two patients, prolonged
      pleural and pericardial effusion occurred. In conclusion, bidirectional cavo
      pulmonary anastomosis with an additional flow source is a good alternative to
      classic or fenestrated Fontan operation in the treatment of complex congenital
      heart disease. The best results are obtained with an additional flow source
      represented by pulmonary artery banding or pulmonary stenosis, due to pulsatility
      and uniform distribution of blood flow in the pulmonary district. Morbility and
      mortality compare favorably with the rates observed in classic or fenestrated
      Fontan operation.

PMID- 9280728
TI  - [Tardive pseudo-ischemic presentation of cardiac rhabdomyoma].
AB  - Rhabdomyoma (RBD) is the commonest cardiac tumour in early childhood. This
      tumour, which is asymptomatic in most patients, is often associated with tuberous
      sclerosis, a multisystem disease that involves mainly the central nervous system.
      RBD, which is generally considered a hamartoma rather than true tumour, often
      regresses spontaneously by age of 2. We present the case of a 19 year-old male
      affected with an RBD diagnosed through transthoracic and transesophageal
      echocardiography and nuclear magnetic resonance imaging, and characterized by
      late cardiac manifestations, including intermittent left bundle branch block and
      a pseudo-ischemic electrocardiographic pattern. These findings may depend on the
      anterobasal septal localization of the RBD.

PMID- 9280729
TI  - [Pulmonary embolism and cerebral stroke from paradoxical embolism in a young
      woman].
AB  - We describe a case of pulmonary embolism and ischemic stroke due to paradoxical
      embolism in a healthy young woman taking oral contraceptives to treat an ovarian
      cyst. It was not possible to identify the site of the thromboembolus. Ultrasound
      techniques played an important role in identifying the peripheral arterial
      obstructions and in diagnosing acute pulmonary hypertension. Transesophageal
      echocardiography provided detailed information on both the morphology and the
      evolution of the atrial thrombus straddling the foramen ovale within the
      aneurysmal interatrial septum. The patient was given anticoagulant treatment,
      initially with heparin and subsequently with warfarin over a period of six
      months. Repeated ultrasound controls showed no thrombus, regression of the signs
      of pulmonary hypertension and, lastly unchanged systemic arterial obstruction.

PMID- 9280730
TI  - [Skeletal musculature modifications and mechanisms of fatigue in chronic heart
      failure].
AB  - The majority of patients with chronic heart failure (CHF) have a decreased
      exercise tolerance. It has not been well established if muscle fatigue is related
      to a peripheral myopathy with specific metabolic, histologic and biochemical
      abnormalities. CHF patients demonstrate depressed oxidative capacity and
      activation of anaerobic glycolysis, leading to a reduction in the energy
      substrates. In addition, the skeletal muscles of the lower limbs demonstrate a
      shift toward type IIb fibers. Many factors, such as prolonged immobilization,
      reduced blood flow and neuroendocrine activation, can be cited in order to
      explain the origin of this myopathy. Recent studies show that immobilization is
      not the only reason for modifications in skeletal muscle composition, since
      patients with disuse atrophy show an increased percentage in myosin heavy chain
      I, while IIb is decreased. The opposite pattern is observed in CHF. It would
      appear that several factors such as deconditioning, prolonged immobilization and
      reduced blood flow, may produce muscular atrophy. The reasons behind specific
      changes in fibre composition may be found in metabolic factors such as insulin
      resistance, TNF levels and dysfunction of the ergo-metabolo muscle receptors.

PMID- 9280731
TI  - [Lights and shadows in the new classification of cardiomyopathy].

PMID- 9280733
TI  - Evolution of transcription-regulating proteins: a brief, critical appraisal.

PMID- 9280732
TI  - [Berengario da Carpi: he illustrates papillary muscles, chorda tendinaeae and
      heart valves].

PMID- 9280734
TI  - [Cervico-uterine cancer and age].
AB  - A retrospective study of 182 cases of invasive squamous cell carcinoma of the
      uterine cervix and 133 cases cases of in situ carcinoma, based on histological
      classification studies and their relation with mean age, during 1985-1994, is
      reported in a second level Hospital in Rio Blanco, Veracruz, Mexico. The mean age
      of invasive cervix carcinoma is 50.2 years and the mean age is not the same in
      the different clinical stages, stage I 45.1 years; stage II 48.6 years; stage III
      54.9 years and stage IV 57.4 years. This finding maybe has clinical importance.
      The mean age of in situ carcinoma is 43.9 years, late when compare with other
      series in the literature. Plan some considerations about mass screening cervical
      cancer program in Mexico.

PMID- 9280735
TI  - [The peritoneal environment: physiopathogenesis of endometriosis].
AB  - In this report an hypothetical model of the pathophysiology of endometriosis is
      reviewed based on recent literature, focusing a variety of factors within the
      specific environment confined by peritoneum, whose alteration has repercussion
      among endometriotic and immune response cells relationships. At this point
      vasoactive substances, cytokines (interleukines and growth factors), and
      menstrual cycle hormones may act as soluble mediators that are able to induce
      several effects over cellular proliferation, growth and differentiation; and
      expression of new antigenic epitopes and cell adhesion molecules. This
      interactions are evident through inflammatory and immune responses, wound repair,
      fibrosis and pelvic adhesion formation, producing an adequate peritoneal
      environment for the initiation, maintenance, and progression of endometriotic
      implants. These finally leads to endometriosis-associated symptoms as pelvic
      pain, dysmenorrhea, dyspareunia and infertility.

PMID- 9280736
TI  - [Delivery after a previous cesarean in the Gyneco-Obsteric Hospital Garza Garcia,
      N.L].
AB  - One hundred and four patients who delivered after a previous cesarean section, at
      Hospital de Ginecoobstetricia de Garza Garcia, N.L., from February 1, 1994 to
      January 31, 1995, were reviewed. The objective for this study was to know materno
      fetal morbi-mortality at our hospital. Age, parity weeks of gestation, cause for
      previous section, delivery culmination, weight and Apgar of products, as well as,
      materno-fetal morbi-mortality, were analyzed. Average age group was 21 to 30
      years with 68.5%. As to parity nulliparae predominated with 48.1%. As to weeks of
      gestation, the most frequent was 37 to 40 weeks, 85.5%. Previous section
      indication was: 1. Pelvic presentation, 2. Fetal stress, 3. Cefalo-pelvic
      disproportion, 4. Premature rupture of membranes, 5. Toxemia. As to deliveries
      outcome, there was dystocia in 86.5%, by profilactic low forceps application in
      81.7%; and mid low in 4.8%. Eutocic delivery, 13.5%. Product weight was 3,000 to
      3,500 g, with 51%. Apgar in 94 products was 8 and 9 at one minute. Maternal
      morbidity was 15.3% being most frequent vaginal tears. There was one case of
      uterine atonia, and one case of dura mater adverted puncture. There were no
      uterine dehiscence nor rupture. Perinatal morbidity was 5.6%. There was no
      perinatal death.

PMID- 9280737
TI  - [Treatment of adnexal tumors with laparoscopy].
AB  - This article shows the experience in 61 patients with adnexal tumors studied from
      June 1988 to June 1994; the origin of the patients in private and semiprivate, to
      whom we practiced a diagnostic and operative laparoscopy (56/61) at the same
      time. The inclusion and exclusion criteria were determined by clinical history
      (past history, age, symptoms, size, etc.), vaginal ultrasonography scan (ascites,
      papillas, cyst's content, etc.), laboratory tests (Ca 125 in postmenopausal
      patients), the macroscopic assessment during the diagnostic laparoscopy,
      transoperative biopsy (19/61) was made in order to confirm the benign findings
      seen before laparoscopy; and the results were accordingly on the 61 cases. The
      cause of consult was infertility in 24/61; 18/61 were primary infertility; 6/61
      were secondary infertility. We did 22 cystectomies and 2 oophorectomies; 10 of
      them became pregnant. 37 from 61 had pain, nine of this group we did an
      oophorectomy (2 by torsion, 3 had hemorrhagic cysts that were ruptured and 4 were
      residual ovary), the rest 28 we performed cystectomy with frank improvement of
      their symptoms. The postoperative diagnosis of the tumors were: luteomas 13/61;
      functional cysts 17/61, Hemorrhagic cysts 8/61; endometriomas 9/61; serous
      cystoadenoma 3/61; mucinous cystoadenoma 1/61; ovaric fibroma 1/61; mature cystic
      teratoma 2/61; residual ovaries 4/61; paraovaric cysts 2/61 and Morgagni's
      hydatide 1/61. It is concluded that if one follows all the correct parameters for
      the evaluation of adnexal tumors, the endoscopic procedure could be safe with the
      benefits of the laparoscopic procedure.

PMID- 9280738
TI  - [Shock in obstetrics. Institutional experience].
AB  - Shock is one of the most difficult problems an obstetrician can face. Hemorrhage
      is the main reason of shock. A descriptive and retrospective research was
      conducted at Instituto Nacional de Perinatologia, from January 1992 to May 1996,
      including all patients admitted to the intensive care unit with diagnosis of
      shock. There were found 90 cases with diagnosis of shock, 82 were hipovolemic,
      and 8 cases had the septic kind of shock. The average of age was 32.2 years, with
      a gestational age between 6.2 to 41.4 weeks . There were 71 healthy patients,
      hypertension was associated to pregnancy in 9 cases, infertility in two,
      myomatosis in 2, and diabetes in 2 more patients. Other 5 cases reported
      different pathologies. The most frequent cause for hipovolemic shock resulted to
      be placenta acreta (40 cases), followed by uterine tone alterations in 37
      patients, ectopic pregnancy in 7, uterine rupture or perforation in 4, and
      vaginal or cervical lacerations in 2. The estimated blood loss varied from 2200
      cc to 6500 cc, and the minimal arterial pressure registered during shock was
      between 40/20 mmHg to 90/60 mmHg. Medical initial assistance consisted in volume
      reposition with crystalloids, globular packages, and plasma expansors in 73
      patients (81.1%). The rest of the patients received in addition coloids,
      platelets and cryoprecipitates. A total of 76 patients required surgical
      intervention consisting in total abdominal hysterectomy. In 5 cases the previous
      surgical procedure was done and ligation of hypogastric vessels was needed.
      Salpingectomy was performed in 5 patients, and rupture or perforation repair in
      3. The average surgery time was 2 hours and 33 minutes. The observed
      complications were 7 cases with abscess of the cupula, consumption coagulopathy
      in 2, 1 vesical quirurgical injury, 1 intestinal occlusion, and 11 vesico-vaginal
      fistula. The average days of hospitalization resulted to be 5. The most frequent
      kind of shock seen by obstetricians is the hipovolemic type, followed by septic
      shock, Volume reposition and restoration of adequate tissue oxygenation is the
      main goal in treatment, and so the rapid and opportune decision for surgery shall
      prevent the patients decriment and maternal mortality.

PMID- 9280739
TI  - [Infection with HTLV virus type I-II in patients with cervico-uterine cancer in
      the Yucatan peninsula, Mexico].
AB  - Southwestern Japan is an endemic zone with high prevalence of HTLV-I infection.
      In addition, a relation between cancer of the cervix and this retrovirus has been
      described. A recent study has demonstrated a low prevalence of HTLV-I/II
      infection in Yucatan, Mexico. However, cancer of the cervix is the most frequent
      oncological disease in this region. The objective of this study was to determine
      the relationship between cancer of the cervix and the HTLV-I/II infection. Sera
      from 123 patients with cancer of the cervix and 662 healthy women were screened
      for antibodies against HTLV-I/II by ELISA and agglutination test (PA). Results
      were confirmed by Western blot (WB). In the confirmed cases the differentiation
      between HTLV-I and HTLV-II was made by synthetic peptides. Only one woman (0.8%)
      had positive results in the patients group and two women (0.3%) had reactivity in
      the control group. In all these cases the antibodies were positive for HTLV-II.
      The prevalence in the group of patients with cancer of the cervix was similar to
      that of the control group. We therefore concluded that in Yucatan, Mexico there
      is no relation between HTLV-I/II infection and cancer of the cervix.

PMID- 9280740
TI  - [Postmenopausal metabolic effects of a synthetic estrogen (tibolone) with a
      characteristic estrogenic action].
AB  - Life expectancy in women has nearly reached 80 yr old, therefore the
      postmenopausal period is considered very important, particularly regarding the
      benefits of hormone replacement therapy. At the present there are several
      therapeutic options in order to protect against the long term complications
      resulting from chronic hypoestrogenism and avoiding some of the side effects
      associated with estrogens medication, tibolone is a synthetic steroid possessing
      mild estrogenic effect and some progestagenic and androgenic actions; moreover
      this steroid does not require to be converted to estradiol. We studied the effect
      of administering tibolone 2.5 mg daily orally during six months to 11
      postmenopausal women in order to analyze any changes on several biochemical
      markers. Estradiol concentrations were not modified although FSH, total
      cholesterol, low density lipoproteins and triglycerides levels decreased.
      Collaterally there was observed an increment in high density lipoproteins and
      sexual hormone binding globulin. It is concluded that tibolone exerts its effect
      directly on specific receptor tissues without being converted to estradiol so
      that this finding may help to understand some of the clinical effects,
      particularly upon mammary gland, endometrium and body weight.

PMID- 9280741
TI  - [The transcendence of prolactin and its relation to the immune response].
AB  - Prolactin is a hormone involved in a variety of physiological processes in male
      and female of several vertebrates species. In mammalian included the human, it
      has been suggested that prolactin plays a role in immunoregulatory mechanism.
      There are some evidence in the sense that exists a notable bidirectional
      interaction between prolactin and the immune systems. This finding has stimulated
      the research on this area. Prolactin has stimulative effects on the lymphocytes
      and on the immune responses, and the cytokines production changes the prolactin
      concentration, so modifying its biological action. These reciprocal effects
      involve the presence of specific receptors. The prolactin receptors have been
      demonstrated on lymphocytes and other accessory cells. This review tries to
      summarize the interaction between immune and neuroendocrine systems and the
      importance of neuroimmune endocrinologic study.

PMID- 9280743
TI  - [Cervical labor induction with prostaglandin E2 in patients with fetal death].
AB  - The objective was to compare the effectiveness and efficacy of prostaglandin E2
      (prepidil gel) plus oxitocin with that of intravenous oxitocin in the treatment
      of delivery induction in patients complicated with fetal death. Fifteen patients
      received prepidil gel plus oxitocin and 15 patients oxitocin. In the treatment
      group only one dosage of 0.5 ng in 2 ml of prepidil gel was administered
      intracervically and simultaneously oxitocin by intravenous infusion, dosage was
      increased 2 mUI/min every 30 minutes. In the control group only intravenous
      oxitocin was administered at the same dosage. The mean duration in hours of
      delivery in the treatment group was 13.1 +/- h and in the control group was 30.9
      +/- 9.1 h. There were statistically significant differences between the groups in
      reduction of delivery duration (p = 0.0007). It is concluded that prostaglandin
      E2 plus oxitocin provide better short-term outcomes than oxitocine treatment and
      gave more short periods of labor in patients with fetal death.

PMID- 9280742
TI  - [Tramadol chlorhydrate in the management of gyneco-obstetric pain].
AB  - An open prospective and longitudinal study was carried out including 102 female
      patients whose pain was due to gyneco-obstetric surgery. The average age was 31.5
      years and the average weight was 67 kg. The tramadol hydrochloride was
      administered as a single 100 mg dose p.o. or i.m., when moderate to intense pain
      was present. At the beginning of the trial, 96.1% of the patients presented
      moderate to very intense pain. At the end of the period of the trial, 74%
      reported none or mild pain. The analgesia began after an average of 17 minutes
      i.m. and 28 minutes p.o. The identified adverse effects were: nausea 1%, vomiting
      5% and somnolence 8%. In accordance with the obtained results, we conclude that
      tramadol chlorhydrate is a good alternative for the treatment of moderate-to
      severe acute pain of obstetric and gynecological origin.

PMID- 9280745
TI  - [Prognosis depends on viral load. AIDS: frequently too much time is wasted].

PMID- 9280744
TI  - [Perinatal conditions of newborns of adolescent mothers in the state of Sinaloa,
      Mexico].
AB  - The objective was to compare perinatal conditions of newborns and obstetric
      complications between a group of adolescent mothers and one of adult mothers. It
      is a retrolective comparative survey, at the General Hospital "Bernardo J.
      Gastelum" SSA and General Hospital IMSS, Sinaloa, Mexico. PATIENTS: 10634
      clinical records of patients in labour at obstetric unit from 1990 to 1994. A
      randomized sample of 215 adolescent pregnant patients and 215 adult pregnant
      patients were selected and the following data were analysed regarding to the
      mother: age, pregnancy outcome and obstetric complications; in regard to the
      newborn: gender, weight, height, cefalic circumference and Apgar score. The mean
      adolescent mother's age was 16 years, and 25 in adult mothers; mean adolescent
      mother newborn birthweight was 3.297 SD 0.414 kg. and in adult mothers was 3.393
      SD 0.591 kg. (p = 0.09), adolescent mothers newborns with Apgar score less than 7
      at first minute was 20% and 5% for adult mothers newborns. Statistically
      significant difference was observed (p = 0.02). There were not statistically
      significant differences between the groups in obstetric outcome and
      complications, birthweight. It was concluded that pregnancy in adolescence it's
      not a risk factor for the mother and the newborn.

PMID- 9280746
TI  - [Therapy of heart failure. I. Definition, pathophysiology, therapy of acute heart
      failure].
AB  - Acute cardiac insufficiency is often the result of acute or chronic overloading
      of the heart due to arterial hypertension, coronary heart disease and/or a
      reduction in ventricular muscle mass following myocardial infarction. Whenever
      possible, treatment should be causal (e.g. treatment of hypertension, operative
      correction of valvular disease). While the incidence of heart failure continues
      to increase, morbidity and mortality associated with the disease process have
      remained essentially unchanged. About 30% of the patients die within the first 12
      months. The prognosis and outcome of heart failure patients strongly correlate
      with markers of neuroendocrine activation. While numerous drugs are capable of
      improving hemodynamics at rest or physical performance, they fall to prolong
      survival. It is hoped, that new pathophysiological information might lead to the
      development of new, effective therapeutic approaches.

PMID- 9280747
TI  - [Therapy of heart failure. II. Therapy of chronic heart failure].
AB  - Current medical treatment of chronic heart failure makes use of a combination of
      diuretics, cardiac glycosides and ACE inhibitors. The latter have improved the
      chances of survival of patients with chronic cardiac insufficiency. The
      combination of hydralazine hydrochloride and isosorbide dinitrate also improves
      survival, but direct comparison of both regimens provided evidence for a less
      favourable effect than that of the ACE inhibitors. Inhibition of neuroendocrine
      activation has been demonstrated only for ACE inhibitors and cardiac glycosides.
      The use of beta blockers represents a new therapeutic strategy that over the long
      term improves cardiomyocyte function, cardiac output at rest, and physical
      performance. For this indication, however, beta blockers should be used with
      extreme caution and at very low initial doses. New approaches in the area of
      clinical research are, for example, calcium sensitizers, modulators of
      intracellular calcium and/or sodium homeostasis, imidazolin receptor antagonists
      with an action on the central nervous system and AT1 receptor antagonists.

PMID- 9280748
TI  - [Heart failure patients are often on the verge of decompensation. Methods for
      reliable management in general practice].

PMID- 9280749
TI  - [Infectiology of the urogenital tract. 5. Therapy of complicated and nosocomial
      urinary tract infections and of unusual pathogens--selection of antibiotics].

PMID- 9280750
TI  - [Noninvasive ventilation in respiratory insufficiency. Indications--methods-
      limits].
AB  - Non-invasive ventilation (NIV) supports alveolar ventilation and represents an
      alternative to conventional invasive mechanical ventilation in suitable cases of
      respiratory failure. It usually takes the form of positive airway pressure
      ventilation, either continuous (CPAP) or bilevel positive airway pressure
      (BiPAP), applied via a nasal or face mask. NIV is capable of increasing arterial
      oxygen saturation and lowering pCO2. Initial controlled studies involving
      patients with severe COLD have shown that, in comparison with conventional
      invasive ventilation, NIV significantly reduces morbidity, mortality and the
      duration of hospitalisation. It has also been used successfully to treat
      respiratory failure due to other pulmonary disorders, neuromuscular diseases,
      during weaning from invasive ventilation, and as "bridging" therapy in patients
      awaiting lung transplantation. However, further studies on indications and
      technique are needed to define more clearly the role of NIV in the clinical
      setting. For the time being, therefore, NIV should be considered to be
      experimental, and conventional mechanical ventilation should always be available
      on standby.

PMID- 9280751
TI  - [Hope for delaying demise].

PMID- 9280752
TI  - Germinal center development.
AB  - Using a set of surface markers including IgD and CD38, human tonsillar B cells
      were classified into discrete subpopulations. Molecular and functional analysis
      allowed us to identify: i) two sets of naive B cells (Bm1 and Bm2); ii) germinal
      center founder cells (Bm2'); iii) an obscure population of germinal center B
      cells, displaying a high load of somatic mutations in IgV genes, C mu to C delta
      switch and preferential Ig lambda light chain usage: these cells may represent
      the precursors of normal and malignant IgD-secreting plasma cells; iv) the
      centroblasts (Bm3) in which somatic mutation machinery is activated; v) the
      centrocytes (Bm4) in which isotype switch occurs; vi) the memory B cells. The
      characterization of these subpopulations showed that: i) programmed cell death is
      set before somatic mutations, possibly providing an efficient way for affinity
      maturation; ii) only high affinity centrocytes are allowed to switch isotype;
      iii) CD40-ligation inhibits plasmacytic differentiation of mature B lymphocytes;
      iv) memory B cells preferentially differentiate into plasma cells; v) IgD isotype
      switch occurs in normal B cells; vi) receptor editing may be induced by somatic
      mutations in germinal centers. We also characterized two types of antigen
      presenting cells in germinal centers: follicular dendritic cells that select high
      affinity B cells, and a new subset of germinal center dendritic cells that
      activate germinal center T cells.

PMID- 9280753
TI  - Differential expression of fibroblast growth factor-2 and receptor by glial cells
      in experimental autoimmune encephalomelitis (EAE)

PMID- 9280754
TI  - Ophthalmomyiasis interna posterior and pigmentary retinopathy of Guam.
AB  - BACKGROUND: Ophthalmomyiasis is ocular invasion by a fly larva. In the United
      States, only two cases of bilateral subretinal ophthalmomyiasis have been
      reported in the literature. Subretinal invasion by the fly larva results in
      characteristic ophthalmoscopic and angiographic findings. Recently, similar
      subretinal changes have been associated with amyotrophic lateral
      sclerosis/Parkinsonism dementia complex (ALS-PDC) in the Chamorro population of
      Guam. This pigmentary retinopathy of Guam (PROG) is generally bilateral in
      presentation, whereas ophthalmomyiasis is generally unilateral. While PROG has
      been associated with neurologic findings, ophthalmomyiasis interna posterior
      (OIP) has not. CASE REPORT: A case of a 65-year-old Asian man with bilateral
      subretinal changes is described. Similarities and differences between
      ophthalmomyiasis and the pigmentary retinopathy of Guam are discussed.
      CONCLUSIONS: Because PROG has been associated with ALS-PDC, a neurologic
      evaluation should be included in the workup of patients suspected of having OIP
      or PROG.

PMID- 9280755
TI  - [Asymptomatic cerebrovascular disorders: their definition and diagnosis].

PMID- 9280757
TI  - [Pathology of asymptomatic cerebrovascular disorders. 2. Cerebrovascular
      lesions].

PMID- 9280756
TI  - [Pathology of asymptomatic cerebrovascular disorders. 1. Lesions involving the
      cerebral parenchyma--pathology and imaging of asymptomatic cerebral infarction].

PMID- 9280758
TI  - [Diagnosis of asymptomatic cerebrovascular disorders. 1. Diagnostic imaging of
      the lesions of the cerebral parenchyma].

PMID- 9280759
TI  - [Diagnosis of asymptomatic cerebrovascular lesions. 2. Non-invasive diagnosis of
      cerebrovascular lesions and cervical vessels].

PMID- 9280760
TI  - [Clinical aspect of asymptomatic cerebral infarction. 1. Risk factors].

PMID- 9280761
TI  - [Clinical aspects of asymptomatic cerebral infarction. 2. Cerebral circulatory
      metabolism].

PMID- 9280762
TI  - [Clinical aspect pf asymptomatic cerebral infarction. 3. Prevention and
      management, with special reference to blood pressure control].

PMID- 9280763
TI  - [Management of asymptomatic cerebrovascular lesions. 1. Surgical indication in
      intact cerebral aneurysm--with special reference to intact, asymptomatic cerebral
      aneurysm].

PMID- 9280764
TI  - [Management of asymptomatic cerebrovascular lesions. 2. Treatment of carotid
      artery diseases].

PMID- 9280765
TI  - [Significance and the current status of examinations of brain diseases
      (multiphasic screening of brain diseases)].

PMID- 9280766
TI  - [Diagnosis and treatment of diseases related to cerebrovascular disorders. 1.
      Vascular parkinsonism--physiopathology and problems].

PMID- 9280767
TI  - [Diagnosis and treatment of diseases related to asymptomatic cerebrovascular
      diseases. 2. Cerebrovascular dementia].

PMID- 9280768
TI  - [Diagnosis and treatment of diseases related to asymptomatic cerebrovascular
      diseases. 3. Binswanger disease].

PMID- 9280769
TI  - [Diagnosis and treatment of diseases related to asymptomatic cerebrovascular
      diseases. 4. Chronic cerebrovascular insufficiency].

PMID- 9280770
TI  - [Asymptomatic cerebrovascular disorders. Discussion].

PMID- 9280771
TI  - [Attrition of goiter and elimination of autoantibody to the thyroid caused by
      treatment of acromegaly: a case study].

PMID- 9280772
TI  - [Giant hepatic cyst successfully treated with injection of a small amount of
      minocycline chloride: study of 3 cases].

PMID- 9280773
TI  - [Case of dilated cardiomyopathy with marked improvement of the cardiac function
      with beta block treatment and exacerbation with the interruption of the
      treatment].

PMID- 9280776
TI  - [Therapeutic guideline for myasthenia gravis].

PMID- 9280774
TI  - [Case of primary postural hypotension without somatic neural symptoms and showing
      a marked reduction in the cardiac isotope uptake in 123 I MIBG scintigraphy].

PMID- 9280775
TI  - [Case of bilateral renal artery stenosis with successful weaning from
      hemodialysis following percutaneous transluminal angioplasty].

PMID- 9280777
TI  - [Treatment of anorexia nervosa].

PMID- 9280778
TI  - 1st International Symposium on Decision Support in Anaesthesia and Intensive
      Care. Mainz, Germany, September 25-28, 1996. Abstracts.

PMID- 9280779
TI  - Forensic autopsies from 1984 to 1993 in Vienna, Austria.
AB  - In Austria every death is subject to an examination by a medical doctor
      authorized by the local health authority. If death is suspected to be natural
      and/or perpetrated by another person, this doctor has to report it to the police.
      Depending on the investigation results, the examining magistrate in charge
      demands a judicial autopsy at the Institute of Forensic Medicine. In 1989, 41
      murders of old patients by nursing assistants in a Viennese public hospital were
      disclosed. The main aim of this retrospective study was to determine any change
      in the demand for forensic autopsies by the Viennese health authority, as well as
      by the criminal court, after 1989. Furthermore, it was of interest to analyze the
      reporting practices of medical doctors examining corpses, as well as thr reaction
      of the criminal court during the study period. After 1989, there was a
      significant increase of non-judicial and judicial autopsies, performed by
      Viennese forensic pathologists. In addition, there was a significant increase of
      reports to the police by coroners as well as by forensic pathologists, paralleled
      by a higher rate of forensic autopsies demanded by the examining magistrate. This
      increase of forensic autopsies took place even though the overall rate of deaths
      in Vienna significantly decreased during the 10-year study period. Thus, the
      disclosure of 41 murders in the Viennese hospital in 1989 can be assumed as a
      turning point in the reporting practices of Viennese coroners, as well as the
      autopsy rate handled by Viennese forensic pathologists.

PMID- 9280781
TI  - Radial keratotomy for low myopia.

PMID- 9280780
TI  - Proceedings of the National Cooperative Growth Study 10th Annual Investigators
      Meeting. San Francisco, California, October 17-20, 1996. Dedicated to the memory
      of Dr. Michael J. Cronin.

PMID- 9280782
TI  - [Some medical remembrances].

PMID- 9280783
TI  - [The Society of Physicians: from yesterday to tomorrow. The missions of the
      Society of Physicians and ordinal elections].

PMID- 9280784
TI  - [Necessity to adapt the functioning of the Society of Physicians to medical and
      social change].

PMID- 9280785
TI  - [Physicians' and scientists' relations with the press].

PMID- 9280786
TI  - [Pioneers in medicine in Lebanon and the first medical associations].

PMID- 9280787
TI  - [Influence of paid work on the perceived health state in women].
AB  - BACKGROUND: Several studies show that paid work has a positive effect on women's
      health, although few studies have shown this relationship in Southern-European
      countries. The aim of this paper was to analyze the self-perceived health status
      of women of Barcelona, Spain according to their type of work (homemaker or
      worker). PATIENTS AND METHODS: Cross sectional study using the 1992 Barcelona
      Health Interview Survey data. SUBJECTS: 1194 women aged 25 to 64 years old.
      Bivariate analysis of women's perceived health status by all other variables. A
      logistic regression model was performed with the dependent variable being women's
      self-perceived health status and the independent variables: type of work
      (homemaker or worker), age, number of chronic diseases, medical care visits,
      children under 12 years and elderly over 65 years living at home and social class
      based on occupation. RESULTS: 15.8% of workers and 31.4% of homemakers reported
      poor self-perceived health status (p < 0.05). This same distribution was
      maintained when adjusting for all independent variables. Social class had an
      important relationship with health, with women from lower social classes
      reporting poorer self-perceived health status than homemakers from upper social
      classes. CONCLUSIONS: The 1992 Barcelona Health Interview Survey analysis
      confirms that in Barcelona as well, paid work has a positive relationship on
      women's self-perceived health status.

PMID- 9280788
TI  - [Factors associated with chronic drug consumption in the elderly].
AB  - BACKGROUND: To determine chronic drug intake in the non-institutionalised elderly
      population and identify factors associated with polypharmacy. PATIENTS AND
      METHODS: Cross-sectional study by means of home interview. 1,015 elderly
      individuals were selected systematically from the 1991 municipal electoral list
      of Albacete, Spain (level of confidence 95%, precision 3%, response rate 93.8%).
      The questionnaire included, disability scales (Minimental test, index of Katz and
      Lawton-Brody, Yesavage scale and DUKE-UNC questionnaire), a self-preceivement of
      health, demographic data and qualitative and quantitative information about drug
      intake. We employed the anatomic classification of drugs to obtain a profile of
      consumption. RESULTS: 75% of those interviewed admitted to taking medication
      chronically (CI 95%: 72.6-78.6). The mean number of drugs was 3.17 +/- 1.94 SD.
      Intake was significantly higher in women (p = 0.01), widows (p = 0.04), those of
      lower social status (p = 0.01), greater age (p < 0.02), and a greater number of
      illnesses (p < 0.001), more frequent users of health resources (p < 0.001), those
      physically dependent (p < 0.001) and those suffering from depression or cognitive
      impairment (p = 0.001). The most commonly taken drugs were: cardioactive drugs
      (22.1%), diuretics (19.4%) and vasodilators (14.2%). Using logistic regression
      analysis we found that the factors associated with higher drug intake were: three
      or more ilnesses (OR = 2.24), poor self-assessed status of health (OR = 1.45),
      physical dependence (OR = 1.59), age greater than 74 years (OR = 1.63),
      depression (OR = 1.68), > or = 4 contacts with health providers over a three
      month period (OR = 2.73) and previous hospital admissions (OR = 2.67).
      CONCLUSIONS: The high intake of drugs by the elderly is determined, among other
      factors, by sociodemographic considerations, the subject's perceived status of
      health and different forms of disability. These factors should be taken into
      account by health professionals when planning a rational use of drugs. There is a
      high consumption of peripheral vasodilators despite their scanty therapeutic
      value.

PMID- 9280789
TI  - [Chronic fatigue syndrome. To be or not to be?].

PMID- 9280790
TI  - [Out-of-home work. Does women's health improve?].

PMID- 9280791
TI  - [Medical education in the threshold of the 20th century].

PMID- 9280792
TI  - [Mad cows, prions, and dementia].

PMID- 9280793
TI  - [Acute hepatitis associated with treatment with minocycline].

PMID- 9280794
TI  - [Bone marrow aplasia and ticlopidine].

PMID- 9280795
TI  - [Does it make sense to use the term senile dementia?].

PMID- 9280796
TI  - [Prevention of infective endocarditis: does the risk population know the
      preventive measures?].

PMID- 9280797
TI  - [Kawasaki syndrome or Q fever?].

PMID- 9280798
TI  - [Lansoprazole-induced hepatitis].

PMID- 9280799
TI  - [Risk factors of arteriopathy of the lower extremities: lipid and not lipid
      factors].
AB  - BACKGROUND: The role of lipoproteins as markers of peripheral arterial disease
      (PAD) is not well defined. METHODS: We measured both lipid and non-lipid risk
      factors in 51 male patients with angiographically proven PAD and in 56 control
      subjects. The independent association of risk factors with PAD was evaluated by
      means of a multiple logistic regression analysis. RESULTS: The levels of
      cholesterol bound to high density lipoprotein (HDLc) and to its subfraction HDL2
      were lower and triglycerides were higher in patients than in control subjects
      (1.0 +/- 0.3 vs 1.2 +/- 0.3, p < 0.003; 0.4 +/- 0.2 vs 0.5 +/- 0.3, p < 0.03; and
      1.8 +/- 1.2 vs 1.3 +/- 0.7, p < 0.02, respectively). Total cholesterol and LDLc
      levels were similar in both groups. In the multiple logistic regression analysis
      that was done with lipid parameters, a statistically significant association of
      triglycerides (OR = 1.73; CI95% = 1.06-2.80) and HDLc (OR = 0.15; CI95% = 0.05
      0.50) with PAD was observed, while HDL subfractions and apolipoproteins were not
      significantly associated. In the multiple logistic regression analysis that was
      done with non-lipid parameters, hypertension (OR = 5.35; CI95% = 1.86-15.4) and
      smoking (packs-year) (OR = 1.04; CI95% = 1.10-1.06) were the only significantly
      associated with PAD. When lipid and non-lipid parameters were included in the
      regression analysis, a statistically significant association between
      hypertension, smoking and HDLc with PAD was observed. CONCLUSIONS: Among lipid
      risk factors, a low HDLc and high triglycerides, and among non-lipid risk factors
      hypertension and smoking, are significantly and independently associated with
      lower limb arteriopathy.

PMID- 9280800
TI  - [Lost opportunities for preventing tuberculosis and derived costs; comment].
AB  - BACKGROUND: We determined the extent to which opportunities for prevention were
      missed among patients with tuberculosis and the costs derived from the lack of
      prevention. METHOD: Descriptive study of patients with active tuberculosis were
      studied in the hospital ward of tuberculosis at the A. Marcide-Novoa Santos
      Centre (Ferrol, Spain), from September of 1991 to August of 1995. Risk factors to
      develop tuberculosis, vaccination with BCG, previous tuberculin skin test and
      previous history of drug prophylaxis or tuberculosis therapy were determined.
      Then, we determined whether they had undergone prevention procedures in
      accordance with current recommendations of the American Thoracic Society. An
      evaluation of the direct and indirect derived costs was carried out in patients
      with any missed opportunity for tuberculosis prevention. RESULTS: Out of 433
      studied patients, 167 (38.6%) got missed any opportunity for prevention. Out of
      167, 29 patients (6.7%) did not complete a previous treatment; 9 (2.1%) did not
      complete drug prophylaxis; 12 (2.8%) with known previous positive tuberculin skin
      test and an indication for drug prophylaxis never received it, and 117 (27%) with
      known indications for screening never received a skin test. 62 patients (53%)
      with known exposure to active pulmonary tuberculosis, and 65 (55.6%) with
      predisposing medical conditions. From the missed opportunities for prevention we
      calculated some direct costs of 116,909,911 pesetas and some indirect costs
      derived from the absence to work (141.9 +/- 114.3 days) and from the death of 6
      patients for tuberculosis. CONCLUSIONS: A large percentage of missed
      opportunities to prevent the disease was found among patients with tuberculosis.
      This means a considerable expense that could have been avoided.

PMID- 9280801
TI  - [Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome (TTP/HUS).
      Description of a series of 35 patients].
AB  - BACKGROUND: Delay in application of massive plasmapheresis is the main
      unfavorable prognostic factor in TTP/HUS, and it is mainly due to difficulties in
      diagnosing this rare illness. The aim of our study is to analyze the clinical
      presentations of TTP/HUS. METHODS: The clinical and laboratory data of 35
      patients with TTP/HUS were analyzed, as well as the treatment used and the
      patients outcome. Time intervals between the beginning of symptoms, the diagnosis
      and the start of treatment were also recorded. RESULTS: The median age was 37
      (range: 11-77) years old and there were 19 (54%) women. The more frequent
      antecedent was chemotherapy with mitomycin C and 5-fluorouracil (7 cases). The
      diagnosis of TTP/HUS was reached after a median of 5 (interval 0-293) days, and
      only 11 (31%) patients were correctly diagnosed in the first medical attendance.
      Hemolytic anemia and thrombocytopenia was the most frequent clinical presentation
      (80% of patients). Neurologic signs or symptoms were found initially in 14
      patients, and oligoanuria in 4. No patient presented initially with the so called
      "clinical pentad" considered to be typical of TTP/HUS. Plasmapheresis was used in
      33 cases. A complete remission was attained in 16, a partial remission in 6, and
      13 patients died. CONCLUSION: Due the fickleness of some clinical manifestations
      considered to be typical of TTP/HUS, these disorders should be considered in
      patients presenting with acute-onset hemolytic anemia and thrombocytopenia.

PMID- 9280802
TI  - [Arteriopathy of the lower limbs].

PMID- 9280803
TI  - [In search of lost opportunities: priorities in the control of tuberculosis].

PMID- 9280804
TI  - [WHO at the cross-road].

PMID- 9280805
TI  - [Anti-retrovirals].

PMID- 9280807
TI  - [Hereditary progressive dystonia (dystonia responding to L-dopa) in a Spanish
      family].

PMID- 9280806
TI  - [A 38-year-old male with progressive tetraparesis].

PMID- 9280808
TI  - [Treatment of enterozoic delirium in a non-psychiatric setting].

PMID- 9280809
TI  - [The evolution of internal medicine in the context of the current health system.
      Chiefs of the Internal Medicine Service of the County Hospitals of Catalonia].

PMID- 9280811
TI  - [Multi-resistant tuberculosis of fatal outcome in a patient without HIV
      infection].

PMID- 9280810
TI  - [IgA nephropathy associated with human immunodeficiency virus infection.
      Description of a case].

PMID- 9280812
TI  - [Cardiac tamponade caused by a rhabdomyosarcoma in the right atrium].

PMID- 9280813
TI  - Beating the malaria parasite at its own game.

PMID- 9280814
TI  - Risk attitude and time discounting.

PMID- 9280815
TI  - Low-molecular-weight heparin in the treatment of patients with venous
      thromboembolism.
AB  - BACKGROUND: Low-molecular-weight heparin is known to be safe and effective for
      the initial treatment of patients with proximal deep-vein thrombosis. However,
      its application to pulmonary embolism or previous episodes of thromboembolism has
      not been studied. METHODS: We randomly assigned 1021 patients with symptomatic
      venous thromboembolism to fixed-dose, subcutaneous low-molecular-weight heparin
      (reviparin sodium) or adjusted-dose, intravenous unfractionated heparin. Oral
      anticoagulant therapy with a coumarin derivative was started concomitantly and
      continued for 12 weeks. Approximately one third of the patients had associated
      pulmonary embolism. The outcome events studied over the 12 weeks were symptomatic
      recurrent venous thromboembolism, major bleeding, and death. We sought to
      determine whether low-molecular-weight heparin is at least equivalent to
      unfractionated heparin in patients with venous thromboembolism. RESULTS: Twenty
      seven of the 510 patients assigned to low-molecular-weight heparin (5.3 percent)
      had recurrent thromboembolic events, as compared with 25 of the 511 patients
      assigned to unfractionated heparin (4.9 percent). The difference of 0.4
      percentage point indicates that the two therapies have equivalent value according
      to our predetermined definition of equivalence. Sixteen patients assigned to low
      molecular-weight heparin (3.1 percent) and 12 patients assigned to unfractionated
      heparin (2.3 percent) had episodes of major bleeding (P= 0.63), and the mortality
      rates in the two groups were 7.1 percent and 7.6 percent, respectively (P=0.89).
      CONCLUSIONS: Fixed-dose, subcutaneous low-molecular-weight heparin is as
      effective and safe as adjusted-dose, intravenous unfractionated heparin for the
      initial management of venous thromboembolism, regardless of whether the patient
      has pulmonary embolism or a history of venous thromboembolism.

PMID- 9280816
TI  - Exercise and breast cancer.

PMID- 9280817
TI  - Exercise and breast cancer.

PMID- 9280818
TI  - Exercise and breast cancer.

PMID- 9280819
TI  - Exercise and breast cancer.

PMID- 9280820
TI  - Ibuprofen in patients with sepsis.

PMID- 9280821
TI  - Autologous bone marrow transplantation versus MACOP-B in B-cell lymphoma.

PMID- 9280822
TI  - Autologous bone marrow transplantation versus MACOP-B in B-cell lymphoma.

PMID- 9280823
TI  - Short-term effects of pamidronate in patients with Gaucher's disease and severe
      skeletal involvement.

PMID- 9280824
TI  - Continuous hemofiltration.

PMID- 9280825
TI  - Continuous hemofiltration.

PMID- 9280826
TI  - Continuous hemofiltration.

PMID- 9280827
TI  - Bedside presentations and patients' perceptions of their medical care.

PMID- 9280828
TI  - Bedside presentations and patients' perceptions of their medical care.

PMID- 9280829
TI  - Bedside presentations and patients' perceptions of their medical care.

PMID- 9280830
TI  - Further cases of valvular heart disease associated with fenfluramine-phentermine.

PMID- 9280832
TI  - Dietary patterns and blood pressure.

PMID- 9280831
TI  - Valvular heart disease associated with dexfenfluramine.

PMID- 9280833
TI  - Dietary patterns and blood pressure.

PMID- 9280834
TI  - Dietary patterns and blood pressure.

PMID- 9280835
TI  - Arguments about tossups.

PMID- 9280837
TI  - Arguments about tossups.

PMID- 9280836
TI  - Arguments about tossups.

PMID- 9280838
TI  - Genetic screening of adolescents.

PMID- 9280839
TI  - Cerebral microsporidiosis due to Encephalitozoon cuniculi.

PMID- 9280840
TI  - Interferon alfa treatment of a patient with eosinophilic cellulitis and HIV
      infection.

PMID- 9280841
TI  - Isolated deficiency of follicle-stimulating hormone re-revisited.

PMID- 9280842
TI  - Human costs of economic sanctions.

PMID- 9280843
TI  - Human costs of economic sanctions.

PMID- 9280844
TI  - Human costs of economic sanctions.

PMID- 9280845
TI  - Human costs of economic sanctions.

PMID- 9280846
TI  - [Structural magnetic resonance tomography in diagnosis and research of Alzheimer
      type dementia].
AB  - One of the most widely used neuroimaging procedures in Psychiatry and Neurology
      is magnetic resonance imaging (MRI). MRI has gained the position of a standard
      investigation in the differential diagnosis of dementia syndromes. In the
      clinical diagnosis of Alzheimer's disease (AD) MRI helps to improve the
      diagnostical accuracy. Recently new MRI-based techniques for performing
      volumetric measurement of cortical and subcortical structures have been
      developed. First reports indicate that MRI-based volumetric measurements can be
      accurate in differentiating AD patients from cognitively normal elderly
      individuals. These new techniques may be useful adjunct in assessing the clinical
      diagnosis of AD. Results could also yield insight in the fundamental pathology of
      the degenerative disease. It is the objective of this chapter to summarize and
      comment on the significance of MRI in the diagnosis and research of AD. Future
      directions are outlined, including the use of microscopic MRI, the
      differentiation of white matter signal hyperintensities and the combined
      evaluation of structural MRI and functional imaging techniques.

PMID- 9280847
TI  - [Reflections on the psychobiology of depression].
AB  - Our present understanding of the disorder "depression" undergoes a changing
      process. Together with the appearance of empirical studies on epidemiology,
      genetics and therapy, the hypothesis of "endogenous" depression has vanished. The
      search for "markers" has been replaced by a growing interest for functional
      connections, thereby generating a variety of possible etiological factors instead
      of the "depressogenic" synapse. Therapy has been revolutionized by the invention
      and the empirical proof of new, short-term psychotherapies. However, the lack of
      a theoretical basis warrants its development as a major endeavor for future
      research.

PMID- 9280848
TI  - [Criminal acts leading to commitment according to psychiatric jurisprudence].
AB  - The analysis of the delinquency bringing disordered offenders into a hospital
      order institution reveals a lot of very conscious and well organized behavior
      during the criminal activity. This must be taken into account in therapy and
      prognosis.

PMID- 9280849
TI  - [Differentiation and therapy of delinquent behavior in borderline disorders.
      Psychodynamic approach].
AB  - In the literature about borderline patients, self-destructive dependency needs
      are described, as well as oral-aggressive root conflicts. Using case studies, the
      author points out that in persons with borderline personality organisation, self
      destructive forms of delinquency are as likely to manifest themselves as
      aggressive forms are. The first form is connected with sexual abuse, the second
      with physical abuse. Therefore, delinquency should be differentiated according to
      the traumatic experiences. Finally, depending on the direction of delinquency
      either directed against oneself or against others-various therapy requirements
      are outlined: delinquency in the sense of self-mutilation primarily requires the
      team to perform a holding function, while aggressive delinquency primarily
      demands a firm setting. The author concludes that the outcome of therapy for
      borderline personality disorders depends on the assessment of the direction of
      the delinquency.

PMID- 9280850
TI  - [The psychiatric illness of Vincent van Gogh].
AB  - Vincent van Gogh's illness has been the object of much speculation. Explanations
      as disparate as acute intermittent porphyria, epilepsy and schizophrenia have
      been proposed. Many of the diagnostic hypotheses, however, are based on partial
      or incomplete consideration of the biography and of the reports of his subjective
      experience in his letters to his brother. Karl Leonhard showed, in a detailed
      analysis of Vincent's biography, that both the course and symptoms of the
      disorder were consistent with the diagnosis of a cycloid psychosis (anxiety
      elation psychosis). In the present paper, the diagnostic judgement of Leonhard is
      described and discussed in the light of independent research on van Gogh's
      letters, his works and biography. The bibliographical sources were investigated
      for information consistent with a cycloid psychosis, but also for information
      that might contradict this hypothesis. The course and symptoms of the disorder
      are presented as comprehensively and systematically as possible and are
      documented with the respective citations. Furthermore, the most important
      diagnoses proposed in the literature are critically discussed. Based on this
      investigation, it was possible to show that only the diagnosis of a cycloid
      psychosis allowed us to connect all the available information to a typical
      psychiatric syndrome.

PMID- 9280851
TI  - [Electroconvulsive therapy in clinical practice].
AB  - Between September 1st, 1994, and the end of August, 1995, 3% of all inpatients
      (21 of 731) were treated with electroconvulsive therapy (ECT) at the Department
      of General Psychiatry at the University Hospital for Psychiatry in Vienna. These
      patients suffered from psychotic and/or therapy-resistant depression (n = 15),
      therapy-resistant schizoaffective psychosis (n = 3), and catatonic schizophrenia
      (n = 3). ECT was administered in short-time anaesthetised and muscle relaxed
      patients. On average, each patient was treated with ECT on 9 non-consecutive
      days. As a rule, electrodes were placed unilaterally over the non-dominant
      hemisphere at the beginning. In four cases electrodes were placed bifronto
      temporally. To be considered as effective the seizure had to last for at least 25
      s. In shorter seizure duration ECT was repeated up to a maximum of three times in
      one session. With this procedure a reduction in clinical global impressions of 
      3.7 points was achieved in ECT-treated patients, who had been considered to be
      "severely" to "most severely" ill according to CGI before starting ECT. ECT
      proved to be effective for treating severe depression and catatonic
      schizophrenia, with only minor and reversible side effects. For establishing a
      favorable relation between good clinical outcome and remarkable few side effects,
      the following factors seem to be of importance, in accordance with the
      literature: (1) application of biphasic short-impulse stimuli in anaesthetised
      and muscle relaxed patients; (2) measurement of static impedance to avoid high
      skin impedance and short circuits. (3) at the beginning of each ECT series
      unilateral electrode placement over the non-dominant hemisphere; (4) ECT three
      times weekly on non-consecutive days.

PMID- 9280853
TI  - [Possibilities for psychotherapy treatment of Alzheimer disease patients in the
      early stage of the disease].
AB  - Psychological changes may precede the neuropsychological symptoms of Alzheimer's
      disease (AD). In addition, early stages of AD are often accompanied by a
      depressive disorder. Therefore, we reasoned whether AD patients might profit from
      psychotherapy. The aim would be to alleviate anxiety, discouragement, and
      inactivation of patients suffering from the early stages of AD. According to
      preliminary experience with a small number of treated cases, interpersonal
      psychotherapy, modified for application in "late-life" (IPT-LL), has been found
      to be useful for the treatment of AD patients. The case of an AD patient is
      presented who underwent psychotherapy for two years. Besides describing the
      special features of such treatment, we address the question of how the next
      relative (e.g., the spouse) may be included in the therapeutic process.

PMID- 9280852
TI  - [Comorbidity of schizophrenia and bulimic anorexia. A case with forensic
      implications].
AB  - We are reporting about a 35 year old female forensic patient who has a double
      diagnosis of anorexia nervosa, bingeeating/purging type, and schizophrenia,
      paranoid type. She repeatedly attacked her therapists and physicians violently.
      Her aggressive state is a result of her psychotic interpretation of her constant
      preoccupation with her body image. We discuss problems concerning antipsychotic
      medication in her case specifically. Furthermore epidemiological aspects of the
      comorbidity of eating disorders and schizophrenia are considered; the incidence
      of schizophrenia in eating disorders seems to be 1-3%, affective and transient
      psychosis being more common; the comorbidity of schizophrenia and bulimia nervosa
      is very rare.

PMID- 9280855
TI  - ["Psychiatric criminal commitment according to section 63 StGB." Comment on the
      contribution by N. Nedopil and R. Muller-Isbern. Legal principles--current status
      -treatment concepts--perspectives].

PMID- 9280854
TI  - [Pathogenicity of Borna disease virus in psychiatric and neurologic disorders of
      humans. Current status of research and critical comments].
AB  - Demonstration of BDV-specific serum antibodies, the isolation of BDV from
      cerebrospinal fluid of neuropsychiatric patients, and the recent demonstration of
      BDV antigen and BDV-RNA in human brain tissues strongly suggest that BDV can
      infect humans. Isolation of BD virus from brain tissue is needed for final proof.
      There is still great controversy about the question of whether BDV antigen, BDV
      RNA or BDV can be detected in peripheral blood monocytes or not. Overall, the
      question of pathogenicity of BDV infection for humans is wide open.
      Investigations of human cerebrospinal fluid indicate that BDV might cause human
      lymphocytic meningoencephalitis and so-called symptomatic psychoses in rare
      cases. Seroepidemiological studies suggest a widely non-specific but possibly
      pathogenic role of BDV in a spectrum of psychiatric disorders.

PMID- 9280856
TI  - ["Serious crimes during treatment in legal psychiatric commitment (section 63
      StGB)."Comment on the contribution by R. Freese et a].

PMID- 9280857
TI  - ["Primary and secondary negative symptoms: a reliable differentiation?" Comment
      on the contribution by W. Barnett et al].

PMID- 9280858
TI  - [Graduate and continuing education seminars in psychiatry and psychotherapy].

PMID- 9280859
TI  - Cortical and subcortical circuits for perception and memory. Special issue in
      honour of Brenda Milner.

PMID- 9280860
TI  - [Patients with carotid stenosis and clinical history negative for coronary
      disease. Usefulness of the ergometric test for the identification of ischemic
      myocardial disease].
AB  - BACKGROUND: The purpose of this study was to evaluate, by Stress-Exercise
      Electrocardiography (SE), the presence of Coronary Artery Disease (CAD) in
      patients with asymptomatic or symptomatic carotid stenosis, who had no history of
      myocardial ischemia. MATERIALS, METHODS AND RESULTS: 133 patients with
      significant carotid stenosis (> = 50%) were consecutively studied according to an
      established vascular protocol. Of 92 patients with no history of CAD, 3 were
      excluded, 4 with bilateral carotid occlusion underwent an Echocardiography-Stress
      Test with Dipyridamole (ED) with negative result. 85 patients underwent a SE. The
      result was negative in 50 patients, positive in 21. In 14 patients the SE was
      uncertain so that they underwent an ED or stress thallium-201 myocardial
      scintigraphy with positive result in 2. No correlation between the degree of
      carotid stenosis and the positive SE in patients with significant carotid artery
      atherosclerosis was found. CONCLUSIONS: Our study demonstrates that about 25% of
      patients with significant asymptomatic and symptomatic carotid stenosis and no
      history of CAD had a latent myocardial ischemia and that the screening of these
      patients with SE is easy, inexpensive and safe and allow us to detect those who
      need a more active treatment.

PMID- 9280861
TI  - [The hepatitis C virus].
AB  - Since 1989, when Choo and coworkers identified a new virus, i.e. virus C, as the
      responsible for most cases of hepatitis non-A, non-B, an impressive number of
      articles upon the biology, epidemiology and physiopathology of this virus has
      been published. The aim of this review is to summarize the most important and
      recent progress on C hepatitis virus such as the genotype heterogeneity,
      phenotype-genotype correlations, infection diffusion and pathology. Moreover, the
      clinical history of the illness, diagnostic methods, correlation between
      different clinical syndromes, such as autoimmune disorders, porphyria,
      cryoglobulinemia and finally the therapeutic strategies based on interferon
      supply, are pointed out.

PMID- 9280862
TI  - [The complement system in kidney diseases].
AB  - The multifaceted relations between complement system and immune-mediated
      nephropathies are reviewed. Several conditions in which either the complement
      activation induces renal damage without hypocomplementemia or hypocomplementemia
      occurs in the absence of circulating IC are reported as well as disorders in
      which immune complexes promote hypocomplementemia. The complement system is
      involved in the clearance of immune complexes, both modifying the immune complex
      size and favouring the physiologic neutralization by the erythrocyte transport
      system. In certain pathological conditions the immune complex intrinsic
      characteristic or genetic abnormalities prevent efficient removal from the blood
      stream. The purpose of the present review is to summarize these conditions,
      briefly describing their pathological consequences, and indicate a simple scheme
      to correctly interpret the biochemical abnormalities of the complement system in
      nephropathology.

PMID- 9280863
TI  - [Role of free radicals, telomeres, and telomerases in aging and cancerogenesis].
AB  - After a rapid examination of a few basic concepts concerning cellular aging and
      programmed cell death, the aging of the tissues and organs, the authors discuss
      the principal theories on senescence. They underline that it is necessary to
      agree in considering the various genetic and epigenetic, endogenous and exogenous
      mechanisms that lead to the complex aging phenomenon multiple and interrelated.
      In particular they stress the hypothesis that senescence can be due to a sum of
      molecular damages caused by free radicals, and to the loss of telomeric DNA.
      Radical reactions can cause mutations, inactivation or a decrease in the turnover
      of mitochondrial DNA which is more vulnerable than the nuclear genoma to the
      attack of mutagenic agents, acting also as a continuous source of initial and/or
      promoting factors of the carcinogenetic process. The somatic cells become
      senescent because during cell division, they lose the mechanisms for the
      lengthening of the telomere. The telomerase prevents the shortening of telomeres
      in neoplastic cells and therefore renders them immortal. Paradoxically the
      protection of the telomere is exactly what must be avoided in the case of tumor
      cells. Recently the demonstration that telomerase is not always involved in the
      restoration of telomere length shows the complexity of the problems connected to
      the cause of senescence.

PMID- 9280864
TI  - [A case of arterial hypertension after use of oral contraceptives].
AB  - It is known that oral contraceptives may induce high blood pressure that usually
      returns to normal values a few weeks after interruption of the drugs, and without
      any specific treatment. The precise mechanism by which oral contraceptives cause
      hypertension is not clear. A severe hypertension and mild heart failure in a
      young woman using oral contraceptives has been observed in the case described.
      The patient needed a careful and prolonged therapy to maintain a normal blood
      pressure.

PMID- 9280865
TI  - [Intracranial meningiomas in the elderly].
AB  - BACKGROUND: Since the introduction of CT and then MRI in the clinical practice,
      the number of elderly patients with intracranial meningiomas observed in
      neurosurgical departments has increased to three/four times. Considering that
      some patients die because of their meningioma and others die with their
      meningioma, the neurosurgeon should not only be able to eradicate surgically the
      lesion, but also to decide if that benign tumor should be treated or not.
      MATERIALS AND METHODS: Forty-three patients with intracranial meningioma, aged
      over 65 were operated upon between 1989 and 1995. They constitute about one
      fourth of all the meningioma-patients operated upon in that period at our
      Department. Main symptoms were focal deficits, psychorganic syndrome, and
      seizures. Mean duration of symptoms was 15 months, with 30% of the histories
      lasting less than 3 months. Associate pathologies were those typical of the
      elderly population with hypertension and senile cardiopathy at the first places.
      Two patients had insulin-dependent diabetes, 2 prostatic carcinoma, and 8 were
      obese. MRI was useful either in depicting the location of the tumor or in helping
      the surgeon to give a correct operative indication and risk evaluation. MRI
      criteria for risk evaluation were severe edema and venous vascular infiltration.
      Forty-five operations were performed. Their duration was not a risk factor by
      itself, it only reflected the difficulty of the removal, due to the location of
      the tumor. Dissection of tumor remnants from main arteries or veins was never
      attempted in this group of patients; total removal was achieved in 75.5% of the
      cases. RESULTS: Immediate postoperative results were good in 71% of cases. Four
      patients died (9%). Long term results were evaluated in 29 patients (mean follow
      up period: 35 months). Twenty-two patients (76%) had excellent or good results, 5
      (17%) fair, and 2 (7%) had severe neurological dysfunctions and needed continuous
      assistance. CONCLUSIONS: Surgical risk factors typical of this age group were
      identified: cranio-spinal location, damage to the cortical or deep venous system,
      severe peritumoral edema, and poor neurological preoperative conditions. Systemic
      risk factors were insulin-dependent diabetes and obesity.

PMID- 9280866
TI  - [Assessment of a patient satisfaction scale in rehabilitation].
AB  - BACKGROUND: A new scale is presented, measuring patients' satisfaction with
      respect to the quality of care during stay in a rehabilitation unit. The
      questionnaire is self-administered and anonymous, and it includes 15 items,
      scored 1 to 4. The cumulative score may thus range 15-60; the higher the score,
      the higher the patient's satisfaction. MATERIALS AND METHODS: The instrument was
      proposed to 175 disabled patients, admitted to a free-standing Centre for
      rehabilitation following neurological or orthopedic impairments. RESULTS: One
      hundred and forty questionnaires were completed. Of these, 131 could be analyzed.
      The mean score was > 3 in every item. Factor analysis disclosed that the
      questionnaire comprises 5 factors, which may be defined as "medical care",
      "physiotherapy", "nursing care", "food" and "physical environment and
      facilities". A satisfactory internal consistency of the items was found (item
      remainder correlations > 0.5, Cronbach alpha > 0.9). This suggests that the scale
      is sufficiently unidimensional to permit cumulative summing of the item scores.
      CONCLUSIONS: The results suggest the content and construct validity of the scale.
      The questionnaire thus merits further psychometric investigation.

PMID- 9280867
TI  - [Horton's giant cell arteritis].
AB  - Giant cell arteritis (GCA) is a spontaneous vasculitic syndrome specifically
      involving the walls of medium and large arteries. While involvement of other
      arterial beds is occasionally identified, this syndrome is most frequently
      recognized when symptomatic involvement of the temporal arteries occurs. Vascular
      lesions are characterized by patchy granulomatous infiltrates composed of T
      cells, macrophages, histiocytes, and giant cells. A better prognosis depends on
      early recognition of the clinical symptoms and prompt treatment. Diagnosis was
      based on the 5 clinical criteria previously used by the American College of
      Rheumatology (1990): 1) age 50 years or older; 2) new localized headache; 3)
      temporal artery tenderness or decrease in temporal artery pulse; 4) erythrocyte
      sedimentation over 50 mm/ hour; 5) abnormal result on artery biopsy. Giant cell
      arteritis was considered a rare disease under age 50; however, it is now known to
      be an important and significant cause of morbidity and mortality in elderly
      people. Therefore early recognition and treatment with corticosteroid are very
      important. There is no general agreement concerning the initial dosage, 40-65
      mg/day are commonly recommended. After a few months the majority of patients can
      be treated with a low maintenance dosage of prednisolone (5 to 7.5 mg/day). The
      mean duration of treatment is about 5 years. The literature is reviewed and the
      clinical implications of this disease are discussed.

PMID- 9280868
TI  - [Extraintestinal Salmonella typhi infection].

PMID- 9280869
TI  - [Local administration of somatostatin in joint diseases in athletes].
AB  - Somatostatin is a hormone produced by the hypothalamus, and is widely diffused
      outside the CNS. It inhibits the secretion of many glands. Recently it has been
      shown that somatostatin has been proposed in the treatment of phlogistic diseases
      of the joints by intra-articular administration. The authors show the results of
      a study conducted in 16 patients (athletes) with arthrosynovitis or tendinitis of
      the knee or of the ankle, in which somatostatin was administered (250
      mg/treatment, 1 treatment/week). Somatostatin significantly reduced pain,
      improved movement function and decreased the effects of pain on daily activities.
      The treatment was very well tolerated locally and generally. In conclusion,
      somatostatin may be considered useful in the treatment of articular and
      tendineous phlogistic diseases, almost in athletes.

PMID- 9280870
TI  - [Severe necrosis during treatment with interferon beta-1b].

PMID- 9280871
TI  - Nonimmune hydrops fetalis, preliminary sequestration++, and favorable neonatal
      outcome.

PMID- 9280872
TI  - [Use of erythropoietin in pregnancy: review of the literature in connection with
      2 cases].
AB  - Recently a growing number of case reports has been published about successful
      pregnancy outcome of dialysed women on recombinant human erythropoietin therapy.
      During pregnancy the maternal demand for erythropoietin may undergo changes, with
      consideration of recombinant human erythropoietin therapy in the early stage of
      renal insufficiency, as is shown by our two reported cases. The use of
      recombinant human erythropoietin seems to be safe for the foetus: it does not
      cross the placental barrier, and therefore lacks any direct foetal effect. The
      treatment of anaemia with recombinant human erythropoietin carries benefits for
      both the mother and foetus. One of the most important preconditions for
      successful recombinant human erythropoietin therapy is adequate iron
      supplementation. Due to the increased risk of pregnancy induced hypertension or
      preeclampsia, there is a need for slow and gradual correction of anaemia, and an
      individually tailored target hematocrit. A close follow up of he patient by the
      obstetrical-nephrological team is essential, with the intensive monitoring of the
      fetuses. In some cases with normal renal function the stimulation of
      erythropoiesis with recombinant human erythropoietin may also be needed during
      the pregnancy.

PMID- 9280873
TI  - [Prolonged oral etoposide therapy in advanced stage lung cancer].
AB  - Authors discuss results of the prolonged oral etoposide treatment of 79 patients
      with advanced stage lung cancer. Thirty patients with small-cell lung cancer were
      treated with Cisplatin in combination with prolonged oral etoposide. Response
      rate was nearly 100%. Most of the patients (24) were in partial remission, and
      the mean survival time was 15 months. Forty-nine patients with non-small cell
      lung cancer were divided at random into two groups: patients in the first group
      (n = 25) were treated with Cisplatin in combination with prolonged oral
      etoposide. In the second group (n = 24) was used only prolonged oral etoposide
      therapy for 14-, or 21 days. Encouraging response rate have been observed with
      long-term daily administration of oral etoposide to treat non-small cell lung
      cancer. In both groups there was a response rate nearly 80%. Most of the patients
      in these two subgroups got into partial remission, and a rest were in stable
      clinical stage (median duration was 5 months). Besides alopecia, which occurred
      in all patients, myelosuppression (agranulocytosis) was the predominate toxicity
      (agranulocytosis in 5 cases), which was affectively treated with combined
      supportive care. Etoposide given by this dose and schedule (100 mg/d for 14 days)
      has activity as first-line systemic therapy in combination with Cisplatin for
      advanced small-cell lung cancer and, has a moderate activity for treatment of non
      small cell lung cancer.

PMID- 9280874
TI  - [Aorto-bi-subclavian bypass in the treatment of left subclavian steal syndrome
      and stenosis of the innominate artery].
AB  - Authors report a case of a left side subclavian steal syndrome, caused by
      occlusion of the subclavian artery, combined with a high grade stenosis of the
      innominate artery. The rare combination of arteriosclerotic lesions of the
      supraaortic arteries have been treated by an aorto-bisubclavian bypass procedure
      performed from a median sternotomy. This is the first publication of this method
      in the Hungarian surgical literature.

PMID- 9280875
TI  - [Cancer screening in Hungary: World Bank supported model programs].
AB  - Since 1995, a model cancer screening program has been in operation in Hungary,
      the overall purpose of which is to promote the establishment of effective and
      efficient screening programs by means of adapting the internationally agreed
      principles of organized screening to the needs and opportunities in Hungary. The
      establishment and operation of a national population-based cancer registration
      system is an other aim of the Program. The model program--financed partly from a
      loan from the World Bank, partly from local funds provided by the Government of
      Hungary--is to develop standard procedure for cervical, breast and colorectal
      screening and to end up with tested recommendations for introduction of organized
      screening of proved effectiveness, integrated into the health care system, on
      country-wide service bases in Hungary.

PMID- 9280876
TI  - [Late onset type I tyrosinemia].
AB  - The authors present a case of tyrosinemia type 1, 3 years old girl at the time of
      diagnosis. The presenting symptoms were 3 times colic, obstipation, acute
      encephalopathy, hypertension, hyponatremia, according to the porphyric crisis.
      Her kidney function tests gave normal results during illness, only once an
      increased calcium turnover was observed. She has no singe of rachitis. Cirrhosis
      of the liver was proved by biopsy because of progressively rising gammaGT and
      alfa-fetoprotein levels. A new ensime-blocker (NTBC) treatment was started in an
      international collaboration. The authors compare the history of this case to that
      of others published in the literature. They summarize the pathomechanism of the
      disease.

PMID- 9280877
TI  - [History of the Kaposi Mor Hospital of Kaposvar].

PMID- 9280878
TI  - [Famous French surgeon from the time of Louis XIV].

PMID- 9280879
TI  - [The concept of spina bifida occulta].

PMID- 9280880
TI  - [Cefaclor allergy and Epstein-Barr virus infection].

PMID- 9280881
TI  - [Determination of dihydropyrimidine dehydrogenase in the prediction of toxic side
      effects of 5-fluorouracil].
AB  - In the chemotherapy of colorectal cancers the most frequently given drug is 5
      fluorouracil, which in certain cases reduces or delays the appearance of the
      local recurrence or metastasis. It is well known that the patient's response to 5
      fluorouracil is very different concerning both, effects and side effects. More
      than 80% of the infused drug is catabolised in the first 20 minutes after the
      treatment. The first and rate limiting enzyme of the catabolism is
      dihydropyrimidine dehydrogenase, which has the highest activity in the liver and
      lymphocytes. The activity of this enzyme shows correlation with the blood level
      of 5-fluorouracil. The deficiency of this enzyme caused severe, in some cases
      lethal toxicity, its congenital deficiency is responsible for familial
      pyrimidinaemia. Authors intended to collect data about the dihydropyrimidine
      dehydrogenase activity of colorectal cancer patients, in order to screen enzyme
      deficiency or very low enzyme activity, which might be in connection with the
      appearance of severe side effects, moreover to determine the optimal dose of 5
      fluorouracil before the treatment. Dihydropyrimidine dehydrogenase activity was
      determined in the lymphocytes of 48 colorectal cancer patients, treated by 5
      fluorouracil, at the beginning of each cytostatic cycle. The enzyme activity of
      the patients was between 1.2 and 24.4 pmol/min/10(6) lymphocyte. The value of the
      enzyme activity fluctuated in a range, characteristic for the individual patients
      and this value was not modified by the 5-fluorouracil treatment. Dividing the
      patients in two groups, low (lower than 5 pmol/min 10(6) lymphocyte) and high
      (higher than 15 pmol/min 10(6) lymphocyte) dihydropirimidine dehydrogenase
      activity, we found that decrease in the white blood cell number and appearance of
      the side effects occurred with much higher frequency in the low activity group
      which resulted in the reduction of the dose or in more serious cases interruption
      of the treatment. Authors conclude that the determination of the
      dihydropyrimidine dehydrogenase activity in the lymphocytes is a valuable method
      in the prediction of the toxic side effects of 5-fluorouracil, in the screening
      of the congenital enzyme deficiency and in the individualization of the 5
      fluorouracil dosage.

PMID- 9280882
TI  - [Lipid lowering treatment in secondary prevention following myocardial infarct].
AB  - 1081 patients treated with myocardial infarction between 1990-1995 were
      investigated retrospectively, 652 (60.3%) of the patients were male and 429
      (39.7%) were female. 154 (14.2%) patients had an early, while 927 (85.5%)
      patients had late myocardial infarction. Of the patients with early myocardial
      infarction 52.3% were smokers, 45.2% had positive family history for ischaemic
      heart disease or acute myocardial infarction. The lipid parameters were analysed
      in detail, because 83.3% of the patients were hyperlipoproteinaemic. The mean
      cholesterol level was 6.91 +/- 1.2 mmol/l, the HDL-C level was 1.19 +/- 0.38
      mmol/l, the triglyceride level was 2.66 +/- 1.8 mmol/l, the LDL-C level was 4.71
      +/- 1.2 mmol/l. The serum LDL-C and the HDL-C levels of the patients with early
      myocardial infarction were compared to the desirable levels suggested for
      secondary prevention. Only 7.2% of the male patients had a cholesterol level
      below 5.2 mmol/l, while all female patients cholesterol levels were above 5.2
      mmol/l. Of the male patients 53.6%, while 78.6% of females had lower triglyceride
      levels than 2.3 mmol/l 78,6% of the male patients had higher protective HDL-C
      level in the optimal range (> 1.1 mmol/l). 12.5 percent of the male patients had
      an LDL-C level lower than the value targeted by secondary prevention (3.0
      mmol/l), while all of the female patients LDL-C levels were higher. The authors
      emphasize the importance of secondary prevention and a more widespread use of
      lipid lowering treatment for patients after acute myocardial infarction.

PMID- 9280883
TI  - [Mandibular reconstruction using a microvascular method in the transplantation of
      a fibular flap].
AB  - The best results in mandibular reconstruction are achieved by transplantation of
      vascularised bone. This transplant has an own blood supply therefore its
      surviving is not influenced by the non-sterile environment of the oral cavity and
      the insufficient blood supply of the operated area (caused by scar or radiation).
      A new promising method for reconstruction of a wide segmented defect of the
      mandible is vascularised fibular flap transplantation. Eight consecutive patients
      treated with fibular flap transplantation in 1993 and 1994 were reviewed. Osteo-
      and osteo-cutan flaps were used for reconstruction of the composite tissue
      defects. The authors report on the surgical technique and their first
      experiences. The authors consider the application of the fibular flap the most
      successful procedure of all types of reconstruction of segmented mandibular
      defect.

PMID- 9280884
TI  - [A specific antidote for the treatment of digitalis poisoning in uremic
      patients].
AB  - Two chronic haemodialyzed patients with digitalis intoxication are reported. One
      of them took digoxin 0.25 mg three times daily for an unknown period and the
      other took digitoxin 0.1 mg twice daily for two weeks. The symptoms of
      intoxication were mainly concealed by uremic syndrome. The diagnosis was
      established by noticed sinus bradycardia, first- and second-degree
      atrioventricular block in ECG and the determination of sera levels of glycosides
      (serum digoxin concentration was 7.36 ng/ml, serum digitoxin concentration was
      46.5 ng/ml) in both cases. Considering the probable long elimination period of
      digitalis and the potentially life-threatening situation the patients were given
      digoxin-specific antibody (Fab) fragments with potassium replacement therapy. The
      symptoms disappeared within a few hours after therapy, side effects and rebound
      toxicity did not develop. In connection with these cases the aim of this report
      is to publish a method which can reverse the life-threatening digitalis
      intoxication in patients suffering from renal failure as well. As to the above
      method, the authors have not found any similar case reports in the Hungarian
      medical literature.

PMID- 9280885
TI  - [Management of diabetes induced by nearly total (95%) pancreatectomy with
      autologous transplantation of Langerhans cells].
AB  - The present report concerns a patient who had undergone nearly total
      pancreatectomy (95%) with pancreatic islet autotransplantation for intractable
      pain caused by obstructive chronic pancreatitis. Islets were prepared by a
      modified collagenase digestion and were cultured in vitro in Eagel's medium in 5%
      CO2 in air at 37 degrees C for 5 days. The resultant preparation, containing
      about 150,000 islets, was injected into the recipient's liver via the umbilical
      vein. No complication occurred from the pancreatectomy or transplant.
      Postoperatively, the patient had complete relief of the abdominal pain, and the
      insulin-independent condition remained with normal fasting blood glucose, and
      hemoglobin A1c for 11 months. Subsequently the fasting hyperglycemia was evident,
      and the patient began oral antidiabetic medication, but 2 year after
      transplantation the insulin-dependent condition demanded exogenous insulin (24
      U). At present the fasting serum C-peptide level is 0.6 ng/ml and the HbA1c of
      5.8% confirms the normoglycemic condition at the same insulin dose. Islet auto
      transplantation should be considered as an adjunct procedure to prevent or
      ameliorate diabetes after total or nearly total pancreatic resection.

PMID- 9280886
TI  - [Comparative study of verapamil and bisoprolol in the secondary prevention of
      myocardial infarction].
AB  - The effect of Ca-antagonist, long-acting verapamil and the selective beta-1
      blocking bisoprolol were investigated and compared in the secondary prevention
      after myocardial infarction. Eighty-seven patients were enrolled, 27 patients
      were not included because of the exclusion criteria, 30 patients were treated
      with verapamil and 30 patients with bisoprolol. During the 540 days of follow up
      period treadmill ergometry and dobutamine stress-test with SPECT investigation
      were performed two times. Both clinically and the data of our investigations the
      effect of the two drugs in the secondary prevention was good, and even at the
      540th day the protective effect was still excellent.

PMID- 9280888
TI  - [Final body height affecting factors in Turner syndrome].
AB  - The treatment with growth hormone of girls with Turner syndrome can only be
      improved further if the factors promoting growth are identified and the treatment
      is adjusted to the patient's special needs. From among these factors the authors
      have examined the correlation of age, bone age, target height and height SDS
      existing at the beginning of the treatment on the one hand, and the projected
      final height determined at the beginning of the treatment on the other.
      Relationship of data were determined with linear regression analysis. According
      to the recent scientific literature early initiation and correct dosage of growth
      hormone treatment is emphasized.

PMID- 9280887
TI  - [Cerebral positron emission tomographic study in systemic lupus erythematosus].
AB  - The cerebral glucose metabolism in eight patients with systemic lupus
      erythematosus (SLE) and in five healthy controls were examined by positron
      emission tomography (PET) using 18-F-labeled deoxy-glucose (FDG) as tracer. One
      of the eight patients had no abnormality by magnetic resonance imaging (MRI),
      three of them had cerebral atrophy and four patients had multiple white matter
      hyperintensities and vascular infarcts in the striatum as assessed by MRI. With
      FDG-PET, inhomogeneous multifocal cerebral glucose hypometabolism was detected,
      more frequently in the temporal lobe of right hemisphere. The PET findings did
      not correlate always with the neurological symptoms. Abnormalities in brain
      metabolism can be detected more frequently by PET, than morphological changes by
      MRI, indicating the involvement of the central nervous system.

PMID- 9280889
TI  - [Histopathological variations in the vitelline duct in heterotopic gastric mucosa
      with special reference to inflammatory changes. (Study of resected specimens from
      1956-1995)].
AB  - Cases of resected vitellointestinal duct remnants (including Meckel's
      diverticula, fistulae and a cyst) diagnosed at the Histopathology Department of
      our hospital between 1956 and 1995 were reviewed for the presence of heterotopic
      gastric mucosa. The review of the files included the whole archives of the Bacs
      Kiskun County Hospital. The files contained 166 records of vitellointestinal duct
      remnant; of these 151 were evaluated and 28 were shown to involve ectopic gastric
      mucosa. Seven of these latter had no assessable surface mucosa, and therefore
      only 21 specimens were evaluated for "gastric" histopathologic changes.
      "Gastritis" was seen in all cases, however the pattern that predominated was that
      of chemical gastritis, which has not yet been documented at this location. It was
      present in 57% of cases and could also account for some symptoms leading to the
      removal of appendices with no histopathologic signs of inflammation. Chronic and
      chronic active gastritis-like inflammation were also demonstrated in some cases.
      Those with moderate or severe activity were associated with peptic ulceration or
      macroerosions. No Helicobacter pylori like organisms were detected with the
      modified Giemsa stain and haematoxylin & eosin stain. No conclusions could be
      drawn regarding the role nonsteroidal anti-inflammatory drugs played in erosive
      gastritis-like diverticulitis because of the lack of information on the use of
      such agents; however erosions were rare (14%). The fact that the proportion of
      ectopic gastric mucosa found in several studies (including this one) is about
      half that suggested by textbooks indicates a need for a more detailed work up of
      resected Meckel's diverticulum and a search for all kinds of gastric pathology if
      gastric heterotopia is present. The identification of chemical gastritis like
      inflammation, which is often viewed and documented as normal mucosa is also
      important in this process.

PMID- 9280891
TI  - The roles of temperature, pH and mosquito factors as triggers of male and female
      gametogenesis of Plasmodium berghei in vitro.
AB  - Developmentally arrested malarial gametocytes undergo gamete formation in the
      mosquito midgut immediately after ingestion of the infected bloodmeal. In the
      rodent malaria parasite Plasmodium berghei male gametogenesis (exflagellation)
      can be induced in vitro by a temperature decrease (from 39 degrees C in the
      vertebrate host to 20 degrees C) and a concomitant pH increase (from 7.3 in mouse
      blood to 8.0). We report the presence of additional Gametocyte Activating
      Factor(s) (GAF) present in Anopheles stephensi tissue extracts, which induce both
      male and female gametogenesis at the otherwise nonpermissive pH of 7.3 in vitro
      but are unable to overcome the low temperature requirement. All constituent
      cellular events of microgametogeneis studied here are induced by the same
      triggers in vitro. A temperature decrease is also required for exflagellation in
      the mosquito midgut. The possible role of GAF as a second obligatory natural
      trigger of gametogenesis is discussed.

PMID- 9280890
TI  - [Pancreatogenic panniculitis based on 2 cases].
AB  - The rarest and hardly known complication of pancreas diseases is the subcutaneous
      nodular fat necrosis, a special type of panniculitides. It is mostly associated
      with pancreatitis and adenocarcinoma of pancreas. Its diagnostic criteria are (1)
      red painless or occasionally painful nodules showing a tendency of coalescence,
      emolition and fistulation on the lower extremities and later anywhere on the
      body, (2) alcoholic case-history, (3) tense, painful joints, (4) elevated
      pancreatic enzyme levels in the blood and urine. Since the underlying pancreas
      diseases may be asymptomatic, the pancreatogen panniculitis should be considered
      as a noteworthy marker of them. The histologic findings are pathognomic. In
      pancreatogen panniculitis in all likelihood the remote foci of adiponecrosis are
      due to the local action of pancreatic lipolytic enzymes carried by the blood. The
      question has not been settled yet. In this article there are presented two cases
      of pancreatogen panniculitis, recognized by the consultant dermatologist.
      Referral diagnoses of both cases were misleading: "erythema nodosum" in the first
      case and "drug eruption" in the second one. The determinant underlying pancreas
      disease in both cases was pancreatitis with pseudocyst resulted from alcoholic
      toxicomany.

PMID- 9280892
TI  - Induction of protective immunity and modulation of granulomatous hypersensitivity
      in mice using PIII, an anionic fraction of Schistosoma mansoni adult worm.
AB  - This study was performed in order to define Schistosoma mansoni antigens that are
      able to function as modulator agents in the granulomatous hypersensitivity to
      parasite eggs in BALB/c and C57BL/6 mice. A fraction of S. mansoni, designated
      PIII, derived from adult worm antigen preparation (SWAP) was obtained using anion
      exchange chromatography on an FPLC system. Immunization of mice with PIII in the
      presence of Corynebacterium parvum and Al(OH)3 as adjuvant induced an immune
      response in this animals as determined by ELISA and spleen cell proliferation
      assays against S. mansoni antigens SEA, SWAP and PIII. In addition, PIII caused a
      significant degree of protection against a challenge infection in immunized mice
      as observed by the decrease on worm burden recovered from the portal system. We
      also showed that PIII profoundly inhibited the vigorous anamnestic granulomatous
      response to eggs in the liver and lungs. This suppression correlated with a
      significant decrease in granuloma size. From these results we conclude that the
      PIII preparation contains antigens that can mediate protective anti-parasite
      immunity and downregulate granulomatous hypersensitivity to S. mansoni eggs.

PMID- 9280893
TI  - Immunolocalization of the fatty acid-binding protein Sj-FABPc within adult
      Schistosoma japonicum.
AB  - This paper describes the first localization study of the 14.7 kDa fatty acid
      binding protein in Schistosoma japonicum (SjFABPc) using transmission electron
      microscopy. A polyclonal antibody raised against recombinant Sj-FABPc was used in
      combination with a colloidal gold marker to determine the distribution of the
      protein within adult parasites. Sj-FABPc was localized within lipid droplets
      below the subtegumental region of the male parasite. Additionally, Sj-FABPc was
      present in the vitelline droplets of the vitelline glands of female parasites.
      There were no detectable levels of Sj-FABPc on the surface or within the tegument
      of male or female parasites. Possible functions of Sj-FABPc within S. japonicum
      and the relevance of these immunolocalization findings in light of the recent
      reports that the homologue Sm-FABPc is an important anti-S. mansoni vaccine
      target molecule are also discussed.

PMID- 9280894
TI  - Molecular karyotype and schizodeme analyses of Trypanosoma cruzi stocks from
      Chilean triatomines.
AB  - Forty-one Trypanosoma cruzi stocks isolated from the Chilean vectors Triatoma
      infestans and Triatoma spinolai were characterized by pulse-field gel
      electrophoresis and Southern blotting with the cruzipain gene, and by schizodeme
      analysis of kinetoplast DNA with EcoRI and Msp I. Seven parasite groups were
      found by molecular karyotype which correlate with schizodeme and multilocus
      enzyme electrophoresis, supporting the concept of clonal propagation for
      Trypanosoma cruzi. A predominant T. cruzi stock was isolated from domiciliary T.
      infestans in several geographical areas of Chile. In contrast, other frequently
      found genotypes were circulating in the sylvatic and domestic transmission cycles
      of specific geographical areas. The greatest heterogeneity of T. cruzi stocks was
      found among sylvatic T. spinolai where at least 4 genotypes were obtained from a
      sample of 16 T. cruzi stocks.

PMID- 9280895
TI  - Cytoskeletal architecture and components involved in the attachment of
      Trypanosoma congolense epimastigotes.
AB  - Scanning and transmission electron microscopy of Trypanosoma congolense
      epimastigotes attached to a plastic substratum shows them to elaborate a complex
      flagellum filament system and plaque with a highly organized structure. Non-ionic
      detergent extraction of these cells shows that the resulting cytoskeletons remain
      attached to the plaque. The subpellicular corset of microtubules can be removed
      by salt or Ca2+ treatment leaving the axoneme, paraflagellar rod, associated
      filaments and the plaque. Neither of these treatments therefore removed the
      plaque-associated material from the substratum. Analysis of these fractions by
      SDS-polyacrylamide gel electrophoresis reveals an abundant 70 kDa protein that is
      highly enriched in the salt extracted 'minimal plaque' structures and appears
      likely to be a major constituent of this structure. These studies reveal that the
      complex filament and microtubule systems of the cytoskeleton involved the
      attachment of trypanosomes to substrata and have established a method of
      biochemical fractionation of the structures and components involved.

PMID- 9280896
TI  - Effects of inhibitors of serine protease, phenoloxidase and dopa decarboxylase on
      the melanization of Dirofilaria immitis microfilariae with Armigeres subalbatus
      haemolymph in vitro.
AB  - The melanization of Dirofilaria immitis microfilariae in Armigeres subalbatus
      haemolymph in vitro is a two-step process. Firstly, the microfilariae are encased
      in a transparent capsule, then the capsule material is melanized later.
      Benzamadine HC1 and p-amidinophenylmethanesulfonyl fluoride, both serine protease
      inhibitors, inhibited the deposition of the transparent capsule material and
      melanization. Diethyldithiocarbamate, a phenoloxidase inhibitor, did not prevent
      the deposition of the transparent capsule material but it did inhibit
      melanization. m-Hydroxybenzylhydrazine, a dopa decarboxylase inhibitor, had no
      inhibitory action on the deposition of the transparent capsule material. However,
      the time for the transparent capsule to become melanized was delayed due to the
      presence of m-hydroxybenzylhydrazine in the test system. Immmunocytochemical
      localization showed that propheoloxidase and/or phenoloxidase was present in the
      transparent capsule material. These results suggest (1) that prophenoloxidase
      cascade is essential in the melanization of microfilariae in mosquitoes and its
      putative activation behaviour is similar to that of other insects and (2) that
      the deposition of transparent capsule material is the result of the activation of
      prophenoloxidase by serine proteases and the melanization of the transparent
      capsule material is due to the presence of active phenoloxidase in capsule.

PMID- 9280898
TI  - Evaluation of an in vitro method to measure behavioural diapause in the tick
      Rhipicephalus appendiculatus (Acarina: Ixodidae) in the laboratory.
AB  - A new method has been developed to investigate behavioral diapause in adult
      Rhipicephalus appendiculatus ticks. It is based on a system of gauze columns in
      which the activity of the ticks can be monitored in the laboratory. An experiment
      was conducted, involving different photoperiodic conditions during the nymph-to
      adult moulting and pre-questing periods, with the aim of comparing the results
      obtained by the in vitro method with those of the standard in vivo method.
      Comparable results were obtained with both methods.

PMID- 9280897
TI  - Ectoparasites of the whitespotted rabbitfish, Siganus sutor (Valenciennes, 1835)
      off the Kenyan Coast: distribution within the host population and site selection
      on the gills.
AB  - Different populations of the whitespotted rabbitfish, Siganus sutor, were
      examined for ectoparasites: adults from the Mombasa area (sampled in December
      1990) and different age classes (adult, subadult and juveniles) from Gazi Bay
      (sampled in December 1992 and August 1993). The most common gill parasites were:
      the monogeneans Pseudohaliotrema sp., Tetrancistrum sigani and Microcotyle
      mouwoi, the copepods Hatschekia sp., Pseudolepeophtheirus sp. and juvenile
      Caligidae, and prazina larvae of the isopod Gnathia sp. Adult siganids had a
      higher parasite load than subadults. Juvenile rabbitfish did not harbour any gill
      parasites. Temporal differences in the parasite load of subadult rabbitfish were
      observed for M. mouwoi (highest in the December samples) and for juvenile
      Caligidae (highest in August). The microhabitat of the 5 most common gill
      parasites was species specific. Most parasite species showed distinct site
      preferences with respect to both gill arches and gill sectors, within the gill
      arches. Niche breadth of the different gill parasite species was independent of
      the abundance of any of the other species present. However, niche breadths of M.
      mouwoi, Tetrancistrum sp. and Hatschekia sp. increased with their own abundance.
      This suggests that interspecific competition for space is low and that
      intraspecific factors could play an important role in the microhabitat choice of
      these gill parasites. The hypothesis that niche restriction leads to higher
      intraspecific contact and an enhancement of chances to mate was tested on 2
      monogenean species, Pseudohaliotrema sp. and Tetrancistrum sigani. Their highly
      aggregated distribution over the gill filaments, leading to increased
      intraspecific contact, is consistent with the hypothesis.

PMID- 9280899
TI  - The telomere binding protein of Euplotes crassus prevents non-specific
      transcription initiation but has no role in positioning transcription initiation
      complexes.
AB  - Model substrates mimicking the telomeric as well as the 5'-untranslated regions
      in front of a 5'-terminal part of a macronuclear gene of Euplotes crassus were
      transcribed in vitro using cellular extracts. The obtained transcripts were
      characterized by primer extension and shown to start at the natural initiation
      points. The situation changed in the absence of telomere binding protein or with
      substrates lacking functional telomeric sequences. In these cases non-specific
      transcription was observed. Since it had been previously found that transcription
      starts are frequently located at an apparently fixed distance from the telomere,
      a model substrate was constructed which carried a duplication of the non
      transcribed region. This resulted in only one transcription start site, the
      position of which was conserved relative to the start of the open reading frame
      but moved away from the telomere by the distance of the duplication.

PMID- 9280900
TI  - [Hypoxic-ischemic brain damage in the newborn].
AB  - The condition referred to as "birth asphyxia" occurs as the result of a hypoxic
      ischaemic insult during the process of labour and delivery. There is no standard
      clinical definition for birth asphyxia, but its incidence in term infants has
      been differently reported to be between 2.9 and 9.0 cases per 1000 deliveries. In
      term infants the risk of death appeared to be closely related to the duration
      that the Apgar score is severely depressed. The best predictor of disability in
      surviving infants is abnormal neurological behavior in the neonatal period
      referred to as hypoxic-ischaemic encephalopathy. Unfortunately, there are no
      generally accepted treatment regimens for birth asphyxia and traditional methods
      for treating hypoxic-ischaemic encephalopathy have not been shown to improve
      outcome.

PMID- 9280903
TI  - [Course of mother-child relations in cases of maternal HIV infection].
AB  - 32 children born from HIV infected mothers (8 HIV infected and 24 seroreverted
      uninfected) were followed up from 1990 to 1995 at the Neurological Institute "C.
      Mondino" in Pavia to study the mother and baby relationship. At the end of the
      follow-up period, from the birth to the end of the second year of age, all
      children had psychosomatic disorders (repeated rejections, anorexia, sleep
      disturbances characterised by difficulty in falling asleep and frequent wake-ups,
      gaseous colics many times during the day). The psychosomatic disorders are
      considered as the result of an early distortion of the mother and baby
      relationship. Thus children born from HIV positive mothers are exposed to the
      possibility of developing psychological problems related to a distorted
      relationship with their mother.

PMID- 9280901
TI  - [Fetal obstructive uropathies: prenatal diagnosis, prenatal and postnatal
      management].
AB  - The urinary tract obstruction may depend by: ureteropelvic junction obstruction,
      vesicoureteric reflux, posterior urethral valves, megacystis-microcolon syndrome.
      Hydronephrosis accounts for 75% of prenatally diagnosed fetal renal abnormalities
      with, in many cases, renal dysplasia, oligohydramnios and Potter's sequence. With
      ultrasound is possible to diagnose most urinary tract obstructions that occurs in
      1% of all pregnancy, but only 0.2% have clinical relevance. We have conceived an
      ultrasonographic protocol to evaluate the renal and urinary tract morphology, the
      cystis, the amniotic fluid and the external genitalia for a more easy
      ultrasonographic diagnosis and for the exact pre and postnatal management.

PMID- 9280902
TI  - [Helicobacter pylori infection as a cause of recurrent abdominal pain in
      children].
AB  - Several reports indicate that Helicobacter pylori plays a role in recurrent
      abdominal pain in children and adolescents. The aim of our study is to determine
      the prevalence of H. pylori among Verona children with and without recurrent
      abdominal pain. 309 patients were tested for the presence of anti-H. pylori IgG
      in a blood sample. Among 43 children with recurrent abdominal pain, the
      prevalence of H. pylori infection was 25.58%, while the prevalence of H. pylori
      infection in children without abdominal symptoms was 4.88%. Sensitivity and
      specificity of serology were respectively 81.8% and 87.5%. We conclude that
      endoscopic examination cannot be replaced by serological test.

PMID- 9280905
TI  - [Management of acute renal failure in hospital practice].
AB  - The incidence of ARF in pediatric population varies according to the definition
      of the syndrome. If the diagnosis is based on a decrease of glomerular filtration
      rate (GFR), possibly accompanied by a decrease of urinary output and the sudden
      change of renal function indexes, then the number of patients which can be
      considered affected by ARF in hospital practice is high, as it comprises all the
      cases with functional impairment of renal function. The availability of tables
      with normal values of serum creatinine for different gender and age and the
      knowledge of the minimal urine output compatible with the normality allows a
      precise diagnosis of ARF. The differential diagnosis of ARF must take into
      account prerenal, renal and postrenal causes. Prerenal and renal ARF may be
      sometimes difficult to differentiate. Indexes such as sodium fractional
      excretion, utilizing urinary to plasma ratios of sodium and creatinine, can be
      helpful: values less than 1 indicate prerenal ARF, more than 2 renal ARF. The
      management of ARF is dependent on the causes of ARF. Prerenal ARF is normally
      treated by measures of volume expansion and/or removal of the underlying cause.
      Renal ARF requires an accurate control of water and electrolyte balance and of
      nutritional status and the prevention or treatment of numerous complications,
      which may worsen the course of the syndrome. Indications to dialysis must be
      evaluated every day and an assessment of nutritional status performed. All the
      factors which may cause hypercatabolism, such as infections, hemorrhage, low
      calorie intake, must be recognized and treated. This approach allows a better
      control of serum urea, potassium, phosphate and acidosis. Nutrition must be
      implemented and an adequate protein and calorie intake must be obtained, through
      spontaneous oral route and, whenever required, enteral and parenteral nutrition.
      In conclusion, patients with mild-degree, mostly of prerenal origin, ARF
      represent a common finding in hospital practice. Identification and prompt
      treatment of the underlying cause is the best prevention of acute tubular
      necrosis. Patients with ARF of renal origin require, in particular, daily
      nutritional assessment and dietary treatment to delay the onset of dialysis.

PMID- 9280904
TI  - [Concentration of blood ICAM-1s in the newborn at risk of infection. A
      prospective study in the first 2 weeks of life].
AB  - We prospectively determined serum concentrations of soluble intercellular
      adhesion molecule 1 (sICAM-1) in the first 2 weeks of life in 32 preterm newborns
      in an attempt to assess whether these concentrations are reliable markers of
      sepsis in newborns at risk of infection. Ten of the study group were normal and
      had been hospitalized only for low birth weight. The remaining 22 presented
      respiratory distress (RDS) and were at even higher risk of infection because they
      required assisted mechanical ventilation and central venous catheterisation for
      parenteral feeding and infusion therapy. Sepsis was diagnosed in 11/22 newborns
      with RDS: in 3 on day 3 and in 8 on day 7. Circulating sICAM-1 concentrations
      were significantly elevated in neonates with RDS (group II) and associated
      infection (group III) compared with normal newborns (group I). However, after day
      3 of life sICAM-1 values were significantly higher in group III than in group II.

PMID- 9280906
TI  - [Evaluation of pediatric patients hospitalized for acute diarrhea from 1990 to
      1996].
AB  - Infectious diarrhea is a common disorder in children in Italy, which may lead to
      hospitalization especially during infancy. In order to obtain data about
      epidemiology and clinic pictures of acute diarrhea, the carts of 1295 paediatric
      outpatients, hospitalized for this pathology in the time between 1990-1996 at the
      Children's Hospital "Meyer" of Florence, were analyzed. An offending organism
      could be isolate in 43.3% of patients; Rotaviruses are the leading cause of
      diarrhea, followed by salmonella spp. Furthermore the role of Campylobacter as
      common bacterial pathogen worldwide has been clarified.

PMID- 9280907
TI  - [The abused child].

PMID- 9280908
TI  - [Head injuries in the pediatric emergency department: a 5-year experience at the
      Pediatric Clinic of Modena].
AB  - We re-evaluated the cases of 436 children with minor head injury admitted in the
      paediatric department of Modena University Hospital in the years 1991-1995 in
      order to revise diagnostic and therapeutic protocols. The external lesions, the
      presence of loss consciousness, vomiting, vegetative reactions, late
      complications, skull X ray, TC scan and EEG were considered. Signs and symptoms
      at admission have been faced with instrumental findings and eventual late
      complications to evaluate the prognostic significance. External lesions and
      vomiting did not correspond to TC scan and EEG positivity or significant
      sequelae. A more close connection to these parameters was found when an history
      of immediate loss of consciousness after trauma, or presence of vegetative
      reactions. Skull X ray appeared useless both to judge the seriousness of the
      lesion and to formulate a prognosis. EEG appeared a sensible tool to evaluate the
      gravity of the trauma and its late consequences. TC has confirmed to be the
      unique instrument able to solve any diagnostic or prognostic doubt. When symptoms
      suggest a bad prognosis, diagnostic procedures should be limited to TC and EEG.
      By our point of view, patients that at admission have a normal neurological
      examination at the Glasgow Coma Scale, no significant symptoms and signs, an
      history of a minor impact dynamic and no signs of child abuse, can be discharged
      from the emergency department; in this case parents should be instructed how to
      do an observation at home in order to evaluate eventual complications.

PMID- 9280909
TI  - [Emergency laboratory in the pediatric module].
AB  - The emergency in the laboratory is a serious problem. The Authors, starting from
      management evaluations, try to analyse the problems related to the urgent
      examinations in the Laboratory of a Pediatric Hospital. They propose executive
      ways for the best working of the same laboratory.

PMID- 9280910
TI  - [Urine analysis in a pediatric laboratory using reagent strips read visually
      (visual dip sticks)].
AB  - The Authors studied the possibility of using some dip sticks visual for
      urinalysis. One hundred of urine samples have been analyzed at the beginning with
      the instrumental laboratory analytical system and then with the dip sticks
      visual; the results put in evidence that there is a real discrepancy as far as
      glucose is concerned. Glucose is overestimated in dip sticks visual method.
      Bilirubin, blood and proteins are in a decreasing order the most different items.
      Concerning to pH the results have been comparable. Specific weight cannot be
      compared to the laboratory method, on the other hand it can be used for
      screening. On the whole the Authors are quite satisfied about dip sticks visual
      method; it can be used in order to accelerate diagnosis and avoid pre-analytical
      mistakes.

PMID- 9280911
TI  - [Ectopia cordis and Cantrell's pentalogy: personal experience and considerations
      on the surgical treatment].
AB  - Clefts of the sternum have always attracted attention whether for pathological
      and physiological features or for research of surgical correction. Two cases of
      sternal cleft, one with partial ectopia cordis, the other with Cantrell's
      pentalogy, are presented. Embryology, strategies and several surgical techniques
      are discussed on the grounds of personal experience. The pediatric surgeon can
      make a choice among a lot of surgical techniques, because the ectopia cordis and
      Cantrell's pentalogy are very uncommon and the surgical treatment has a difficult
      codification. The knowledge of several methods of surgical correction is
      necessary to reduce high mortality of ectopia cordis and Cantrell's pentalogy.
      Primary repair in the neonatal period is the best type of management for these
      rare conditions, because simple closure of the sternal defect during the first
      month of life avoids the more complex reconstruction necessary in older children.

PMID- 9280913
TI  - [Benign paroxysmal torticollis in childhood].
AB  - The Author describes one case of a male infant aged 12 months with recurrent
      short lasting episodes of torticollis, accompanied by vomiting, pallor, vacuous
      stare, sudden cry, without any electroencephalographical or neuroradiological
      alterations. At first torticollis attacks appeared with monthly frequency,
      afterwards they began to become less frequent and at last they disappeared at the
      age of about 30 months.

PMID- 9280912
TI  - [Empty sella syndrome: 2 cases to show its polymorphism].
AB  - Magnetic resonance imaging has proved to be the best technique to visualise the
      sella and juxtasellar area and it is used successfully to evaluate children with
      hypopituitarism or other endocraniological disorders in this area. The Authors
      present two cases of "empty sella syndrome", both characterized by growth hormone
      deficiency associated with precocious puberty in one case and with delayed
      puberty in the other one. The Authors stress the importance of magnetic resonance
      imaging in defining the morphological aspects of the hypothalamo-pituitary region
      and that empty sella can be associated either with pituitary hypofunction or
      hyperfunction.

PMID- 9280914
TI  - [Chronic renal failure secondary to vesicoureteral reflux: is the prevention
      possible?].
AB  - Vesicoureteral reflux (VUR) is the commonest cause of end-stage renal failure
      reported by the ITALKID (Italian Register of Chronic Renal Failure) (CRF) in
      children (0-15 years). Herein we report 131 children (53 M and 78 F) with a
      diagnosis of VUR made in our Centre between 1987 and 1994. Diagnosis was made in
      69% of cases (85/131) during the 1st year of life and in 31% of cases (47/131)
      afterwards. VUR was demonstrated following a prenatal ultrasonography suspicion
      in 24/131 and after symptoms such as urinary tract infection (94/131) and poor
      growth (6/131). 75/131 of patients were treated conservatively (continuous
      chemoprophylaxis) while 56/131 underwent an antireflux surgery. CRF was found in
      14% (19/131) of cases even though the diagnosis of VUR was performed in most of
      the cases (79%) during the 1st year of life. In conclusion prenatal
      ultrasonography has a low sensibility in the diagnosis of VUR. In addition, an
      early diagnosis made during the 1st year of life do not prevent CRF. The study
      was carried out in a Centre where patients with urological problems are referred
      from a large part of Northern East of Italy and this may explain the high
      prevalence of CRF and of children receiving a surgical treatment.

PMID- 9280915
TI  - [Colles' fracture in a girl after fulguration].
AB  - In the present study we describe the case of a 11 years old child, female, who
      was accidentally fulgurated by the left arm and after has presented an episode of
      pallor, shaking, confusion, throbbing and tingle of the arms. For this reason she
      was admitted in our Department of Pediatrics, University of Rome "La Sapienza".
      The child presented also a moderate pain at the left wrist. For this reason was
      performed a wrist X Ray which showed an incomplete fracture of the distal
      extremity of the radial diaphysis, with a small ulnar infraction of the same
      side. Life parameters and the ECG were normal so as the blood exams, in
      particular the CPK and the LDH (in fact, they can be indication of muscular
      necrosis). In summary the Authors with this study would like to remark the
      necessity of to suspect a fracture in the place of admittance of the electric
      current, even if not immediately appear clean signs of oedema, pain and
      functional impotence.

PMID- 9280917
TI  - [Comprehensive psychiatry and the graduate education at Kitasato University].

PMID- 9280916
TI  - [Reality and task of psychiatry education at Matsuzawa Hospital in Tokyo].

PMID- 9280918
TI  - [Problems in establishment of psychiatry specialty certification--viewed from an
      experience at Musashi National Hospital in Japan].

PMID- 9280919
TI  - [Psychiatry specialty board certification and graduate medical education at a
      university hospital in Japan].

PMID- 9280922
TI  - [Treatment of the herniated lumbar disk. Presentation of 182 operated patients].
AB  - We have reviewed the signs and symptoms of a herniated lumbar disc and the
      indications for medical an/or surgical treatment. We have also considered the
      different surgical options. The author presents his own statistics: 182 patients
      operated (210 surgical Interventions); in 167 patients (91.8%) the herniated disc
      was in the L4-5, L5-S1 space or in both, in eight (4.4%) in L3-4, in seven (3.8%)
      in L2-3 and L3-4.

PMID- 9280921
TI  - [Analysis of reality in psychiatry specialty certification--viewed from
      experience in pediatrics (discussion)].

PMID- 9280920
TI  - [Survey on physicians' attitude toward specialty certification-- report by
      specialty board].

PMID- 9280923
TI  - [Immunologic aspects related to hemoglobinopathic diseases].
AB  - The records of 96 patients with sickle cell disease were studied in relation to
      various immunological parameters. Age, sex, levels of total and fractionated
      serum protein and immunoglobulins, serum complements, antierythrocytic
      antibodies, circulating immune complexes, antiviral antibodies and lymphoid
      populations were taken into account. No major alterations in humoral immunity
      were found in this group of panamanian sickle cell patient.

PMID- 9280924
TI  - [Workshop on sexuality and its effectiveness as an alternative to sexual
      education directed to adolescents].
AB  - We present the experience accumulated during 3 years of having performed 10
      workshops related to the topics of Sexuality and Affection, offered to 175
      adolescents between the ages of 13 and 19 years, from public schools within the
      Panama, City Metropolitan Area and who correspond to different socioeconomical
      strata. Analytical information provided from the results of two questionnaires
      related to knowledge about the two topics, applied prior to and after the
      workshops is also offered.

PMID- 9280925
TI  - [Treatment of focal dystonia with botulinic toxin].
AB  - Dystonia is a neurologic disease characterized by involuntary repetitive muscular
      contractions which frequently causes torsion, spasmodic movements or abnormal
      postures. Pharmacologic and surgical treatment had been unsatisfactory in the
      majority of the cases. Intramuscular botulinic toxin application in focal
      dystonia disorders, achieve relief in approximately 90% of the cases by
      quimiodenervation. We included 35 patients with focal dystonia treated between
      November 1994 through June 1996: 14 facial hemispasm, nine blepharospasm, five
      cervical dystonia, two writer's cramps, one oromandibular dystonia and four
      patients with mixed focal dystonia. Improvement between 50-90% was observed in
      32/34 (94%) of the patients; one case (2.8%) with therapeutic failure and one
      case (2.8%) never returned to quantify the response. Actually, botulinic toxin is
      the first choice treatment of focal dystonia and other diseases related to
      involuntary muscle spasm.

PMID- 9280926
TI  - [Re-emergence of dengue in Panama].
AB  - The dengue surveillance system in Panama during the 1994 and 1995 epidemics shows
      the following results: In 1994 we registered 793 dengue cases and a year after
      3,083 dengue cases, with three dengue haemorrhagic cases (one death). To estimate
      the accumulated incidence rates in 1994-1995 period, we consolidated the cases.
      The highest risk of dengue and the highest dengue haemorrhagic propension were
      observed in: West Panama (709.49 per 100,000 persons), Los Santos (405.74 per
      100,000 persons), Herrera (337.62 per 100,000), Metropolitana (126.98 per
      100,000) and San Miguelito (125.10 per 100,000 persons).

PMID- 9280927
TI  - [Bilateral Wilms' tumor. Current treatment].
AB  - Partial nephrectomy combined with chemotherapy has been the most effective
      treatment in bilateral Wilms tumors. We present two cases. The bilateral
      synchronous tumor are present in 4.2% and the metachronous tumor in 1.6%, in the
      world statistics. The synchronous bilateral Wilms tumor, Stage V, have an
      excellent prognosis: over 87% survival, compared to 40% of the metachronous
      bilateral Wilms tumors.

PMID- 9280928
TI  - [AIDS in children: diagnostic imaging of pulmonary and abdominal lesions. Review
      of the literature and personal experience].

PMID- 9280930
TI  - [Static functional study with magnetic resonance of anterior shoulder
      instability].
AB  - We studied the glenohumeral joint, in its different components, with cine MRI.
      Ten asymptomatic volunteers and 6 patients with recurrent shoulder instability
      were examined with T2-weighted GE MR sequences on the axial plane with the
      subjects' arms rotated in different positions. The sections corresponding to the
      subcoracoid space and bicipital groove were recorded in closed-loop video format
      for cine display. Normal morphological glenoid labrum changes were demonstrated
      in different degrees of humerus rotation. The subscapularis tendon and the
      capsule were redundant and infolded toward the joint on internal rotation in 4/6
      patients. We found capsular detachment in 2 patients, humeral head subluxation in
      3 and subcoracoid impingement in 2 patients. Cine MRI permitted the accurate
      study of the changes in the glenoid labrum, capsule and subscapularis tendon in
      all patients and it also showed narrowed coracohumeral distance (< 11 mm) on
      internal rotation.

PMID- 9280929
TI  - [Comparison of magnetic resonance Spin-echo sequences and fat-suppressed
      sequences in bone diseases].
AB  - Thirty-two patients affected with skeletal conditions were examined with MRI
      using Short TI Inversion Recovery sequence and Spectral Presaturation with
      Inversion Recovery (SPIR) sequence as well as Spin-Echo (SE) T1-weighted sequence
      and Fast Spin-Echo (FSE) T2-weighted sequence to compare their value in the
      assessment of skeletal lesions. SPIR sequence was performed after intravenous
      injection of Gd-DTPA. The lesions included primary bone tumors (10 cases: 1
      osteosarcoma, 1 periosteal sarcoma, 1 Ewing's sarcoma, 1 chondrosarcoma, 2 non
      ossifying fibromas, 1 chondroma, 1 chondromyxoid fibroma, 1 desmoplastic fibroma
      and 1 bone cyst), metastases (7 cases: 3 prostate, 3 breast, 1 lung-squamous cell
      carcinoma), infections (12 cases: 9 osteomyelitis, 3 spondylodiscitis),
      sacroiliitis (1 case) and posttraumatic bone bruise (2 cases of bone marrow
      edema). The four sequences were compared by using both qualitative and
      quantitative evaluation. Qualitative evaluation showed that STIR sequence was
      better than SPIR sequence (performed with Gd-DTPA) for lesion conspicuity (p <
      .016) and for signal intensity uniformity (p < .03). Compared with SE T1 and FSE
      T2 sequences, fat-suppressed sequences were superior for conspicuity, margins,
      and extension of the lesions (range of p < .001-.017). Only SPIR with Gd-DTPA
      sequence, compared with SE T1 sequence for lesion conspicuity was not
      statistically significantly different. Quantitative evaluation showed
      statistically significant higher values of percent contrast (%C) and contrast-to
      noise ratio (C/N) for STIR sequence compared with SPIR sequence (%C p < .004; C/N
      p < .040). This study suggests that STIR sequence and SE T1-weighted sequence
      provide high sensitivity in lesion detection and good anatomical definition. The
      use of a fat-suppressed sequence with Gd-DTPA can be useful for lesion
      characterization.

PMID- 9280931
TI  - [Magnetic resonance of the brain: comparative assessment of conventional
      sequences versus fast sequences].
AB  - The conventional Spin-Echo sequences have been the most used acquisition
      techniques on Magnetic Resonance Imaging (MRI) of the brain, since the beginning
      of 1990s. Recently, however, technological developments proposed such new fast
      acquisition techniques, with a dramatic reduction in acquisition time as Gradient
      Echo, Turbo Spin Echo, Gradient Spin Echo ed Echo Planar sequences. We
      investigated the comparative adequacy of the new fast sequences, in brain MR
      studies versus conventional sequences, on medium field strength MR equipment (.5
      T). On in vitro exams S/N ratio was evaluated and on in vivo study C/N ratio
      between white substance grey substance and fluid were evaluated, in 15 healthy
      volunteers. All the exams were carried out on Philips NT5 Gyroscan MR unit
      operating at .5 T, with 15 mT/m power gradients. Both conventional and fast
      sequences Spin-Echo (SE), Inversion Recovery (IR), Gradient-Echo (GE), Turbo Spin
      Echo (TSE), Gradient Spin-Echo (GRASE) and Echo Planar (EPI), all optimized to
      obtain T1, T2 and T1-IR weighted images, were performed. The sequences were
      evaluated separately comparing different acquisition techniques relative to the
      same type of contrast (T1, T2, and T1-IR). The results indicate the superiority
      of the fast acquisition techniques, both in terms of quality and acquisition
      times, except for T1-weighted images, where the conventional Spin-Echo sequences
      confirmed to be superior. In conclusion, the present study suggests that fast
      acquisition techniques can improve the conventional protocol of sequences, in the
      anatomical representation of the normal brain even with medium field strength
      equipment only on T2 and T1-IR weighted images. On T1-weighted imaging
      conventional SE acquisition technique is still the best choice. The time saving
      obtained with fast sequences can therefore be used for an overall improvement in
      the quality of images, and to apply accessory acquisition plans on routine exams.

PMID- 9280932
TI  - [Slow-resolution pneumonia: radiologic and tomodensitometric features].
AB  - To assess the radiologic findings of unresolving pneumonias (radiologic signs not
      normalized at the end of the fourth week of antibiotic therapy), the radiologic
      (192) and CT examinations (33) of 50 patients were reviewed, for a total of 64
      pulmonary parenchymal lesions. These lesions presented as masses (3; 4.6%),
      parenchymal thickenings with aerial bronchogram (41; 63.7%), sometimes escavated
      (4; 10%), alveolar ground glass alterations (4; 6.2%), more frequent on the right
      side (49; 73%), mostly in the upper lobe (21; 32.8%). Pleural effusion was
      demonstrated in 16 patients (32%) and lymphadenopathies were shown in 8 patients
      (8%). When possible, the responsible germ was isolated with microbiological
      expectoration test (14; 35.3%), bronchoscopy associated with bronchoalveolar
      lavage (7; 37.5%) and needle biopsy in the mass (2; 5%). The germs were Candida
      (9), haemophilus influentiae (1), Klebsiella (1), pneumococcus (1), Pseudomonas
      (3), Staphylococcus aureus (4), streptococcus alpha hemoliticus (6). There are no
      typical radiologic and CT findings for the described lesions in different
      patients and different germs can produce the same changes. Therefore, pulmonary
      inflammations must be followed to their complete resolution, to rule out the
      chance of a neoplastic process (obstructive pneumonia). The first radiologic
      control must be made at least 15 days after the beginning of therapy for the
      anatomo-pathologic processes of recovery to show radiographically. CT can be
      fundamental in the differential diagnosis with neoplasm, in unresolving
      pneumonia, to study the tracheobronchial tree, to study lymphadenopathies and to
      guide needle biopsy.

PMID- 9280933
TI  - [Lung tuberculosis in HIV positive patients. Clinico-radiologic correlations].
AB  - We investigated the radiologic features of pulmonary tuberculosis in HIV+
      patients. SUBJECTS AND METHODS: 24 cases of pulmonary tuberculosis in HIV+
      patients were studied (17 men and 7 women, average age: 38 years). The study
      includes 19 drug addicts, 3 homosexuals, 1 polytransfused subject and 1 patient
      not belonging to the categories considered at risk). Three subgroups were
      identified by the CD4/mm3 cell count (< 200, 200-500, > 500). RESULTS: In our 24
      patients, we identified 37 radiologic manifestations (in 13 cases associated in
      the same patient), with 6 cases of bilateral pulmonary and 9 atypical
      localizations. In detail: 10 consolidations, 7 productive (miliary) cavitations,
      8 mediastinal lymphadenitis, 3 extrapulmonary forms and 4 cases with no chest X
      ray alterations. There is a major frequency of consolidations and cavitations in
      the patients with CD4 > 200 and a major frequency of productive forms,
      lymphadenitis and extrapulmonary localizations in the subjects with CD4 < 200. We
      observed no cases of tuberculosis in patients with CD4 > 500. The medical therapy
      is usually more effective in the more immunocompetent subjects and, anyway, in
      the exudative forms, improving in 35% of cases, than in the productive and
      disseminated forms improving in 6% of cases only. DISCUSSION AND CONCLUSIONS:
      Only the severely immunodeficient HIV+ patients (CD4 < 500) are affected with
      tuberculosis. There exists a significant rate of parenchymal consolidations and
      tisiogenic forms in subjects with CD4 > 200 and a high rate of miliary forms,
      lymphadenitis and extrapulmonary localizations in patients with low cell count (<
      200). The medical therapy is more effective in the more immunocompetent subjects
      and, anyway, in the exudative forms, than in the productive and disseminated
      forms. Finally, atypical localization of pulmonary tuberculosis are frequent in
      HIV patients.

PMID- 9280934
TI  - [Diagnostic imaging and therapeutic implications in lung infections in patients
      with HIV-1 infection].
AB  - We studied retrospectively 132 episodes of infectious pneumonias in 89 patients
      examined from 1990 to 1995. Pneumocystis carinii was found to be the most common
      cause of pneumonia (33 patients). The other causes were: Streptococcus pneumoniae
      (15), Mycobacterium tuberculosis (14), Pseudomonas aeruginosa (8), Staphylococcus
      aureus (5), Cytomegalovirus (4), Haemophilus influentiae (4), Mycobacterium avium
      intracellulare (2), Klebsiella pneumoniae (2), E. coli (2), Serratia marcescens
      (1). No etiologic agent was found in 40 cases. We stress the need of a more
      frequent use of invasive diagnostic procedures in the study of focal lung
      consolidations because this radiologic sign is highly aspecific and may be caused
      by too many different pathogenic agents, needing different therapies-i.e.,
      Streptococcus pneumoniae (15 cases), Pseudomonas aeruginosa (8), Staphylococcus
      aureus (5), Klebsiella pneumoniae (2), Escherichia coli (2), Pneumocystis
      carinii, Serratia marcescens and Haemophilus influentiae (1). Since there is an
      increase in mortality among patients treated with empiric antibiotic therapy, we
      stress the need of the routinary use of bronchoalveolar lavage in HIV+ patients
      with lung consolidation to perform specific therapy. Moreover, Pneumocystis
      carinii is by far the most frequent cause of diffuse interstitial infiltrates,
      and PCP has very suggestive clinical (dyspnea), radiologic (diffuse perihilar
      interstitial infiltrates; ground glass opacities; pneumatoceles) and laboratory
      (CD3+CD4 < 200/mcl; LDH > 600 UI/dl; PO2 < 70 mmHg) patterns, always related to
      the discovery of Pneumocystis carinii in escreatum. Thus, we decided to treat 15
      patients with specific therapy for Pneumocystis carinii pneumonia with the above
      diagnostic algorithm, obtaining in all of them complete clinical and radiologic
      recovery. To conclude, in critical patients, invasive procedures should be
      performed only in the cases in which PCP is clinically improbable.

PMID- 9280935
TI  - [Assessment of contrast enhancement in solitary pulmonary nodules studied with
      spiral computerized tomography. Preliminary results].
AB  - This study was aimed at assessing the clinical usefulness of measuring the
      contrast enhancement (CE) of solitary pulmonary nodules (SPN) in distinguishing
      benign from malignant lesions. We used spiral CT to study prospectively 35
      pulmonary lesions presenting as SPNs < 30 mm phi; we evaluated the CE of the
      nodules 120 minutes after the administration of 100 mL of nonionic contrast
      material (= 30 grams of iodine), at 2 mL/s. The final diagnosis of the 35 SPNs
      was made at surgery (27 cases); positive sputum cytology (2 cases), 12 months'
      follow-up (5 cases) or fine-needle aspiration biopsy and 6 months' follow-up (1
      case). Thus, 25 of 35 SPNs proved malignant (11 adenocarcinomas, 5 squamous cell
      carcinoma, 2 large cell carcinomas, 2 carcinoids, 1 small cell carcinoma, 2 cases
      with positive sputum cytology, 2 metastases) and the extant 10 of 35 proved
      benign. Malignant nodules enhanced markedly more (mean value: 36.8 HU) more than
      benign lesions (mean value: 18.6 HU). CE exceeded 20 HU in 23/25 malignant
      nodules and did not in 2/25; it did not exceed 20 HU in 6/10 benign nodules and
      did in 4/10. With 20 HU as the threshold value for a positive test (malignancy),
      sensitivity was 92%, specificity 60% and accuracy 83%; positive and negative
      predictive values were 85% and 75%, respectively. In conclusion, CE evaluation is
      a sensitive, although not very specific, indicator of malignancy in SPNs.

PMID- 9280936
TI  - [Description and preliminary clinical assessment of a digital chest radiographic
      system with selenium detector (Thoravision)].
AB  - The authors describe an innovative digital chest imaging system (Thoravision,
      Philips Medical System) based on a selenium detector directly converting X-rays
      in electric charges detectable by electrometers, amplified and digitalized to be
      sent to the imaging processor. The study was performed on a series of up to 7000
      digital chest X-ray examinations and a sample of 173 cases was selected on the
      basis of particular diseases and pathologic patterns. In the latter case, digital
      and conventional radiographic techniques were compared. According to this
      analysis, the digital system was slightly superior in detecting anatomical
      details, small pleural effusions (3 cases) and slight low contrast interstitial
      pathologic changes, mainly in apical (12 cases) and retrocardiac (19 cases) lung
      areas. The conventional screen-film system better showed small hilar
      calcifications (2 cases). From the protection viewpoint, at equivalent entrance
      doses, .15-.26. Gy/cm2 of dose-area product (DAP) values were reported with the
      digital system, using a tension of 150 kV in orthogonal projections, which are
      considerably lower than .25-.70 Gy/cm2 measured with the conventional technique.
      Moreover, Thoravision permitted to perform up to 100 exposures/hour, using a
      phantom, and 15-20 digital chest examinations/hour, versus the average 12-15 with
      the conventional screen-film system. The initial results are very encouraging
      from the clinical and cost-effectiveness viewpoints, thanks to higher Thoravision
      productivity and to exam optimization, even though wider and prolonged experience
      plus a careful study of diagnostic accuracy, sensitivity and specificity in each
      group of chest conditions is advisable, to assess the real innovative impact of
      this digital chest imaging system.

PMID- 9280937
TI  - [Vein patency in patients with pacemaker implanted via subclavian vein: digital
      phlebography assessment].
AB  - Venous thrombosis is a well-known complication of permanent cardiac pacemaker
      implantation, particularly, chronic occlusion of the subclavian vein is reported
      to occur in 20-33% of the cases where the percutaneous approach is performed. We
      examined 135 asymptomatic patients with digital venography to asses the frequency
      of venous thromboses causing stenosis and occlusion of the subclavian or
      anonymous arteries in pacemaker carriers. We considered both one- (44) and two
      chamber (91) pacemakers and investigated a possible statistically significant
      difference between them: we found 21 venous thromboses (15%), seven of them in
      one-chamber pacemakers (15.9%) and 14 two-chambers pacemakers (15.3%). None of
      our 94 male and 41 female patients was on anticoagulants or had any evidence of
      coagulation disorders. Venography was performed 39.3 months (mean) after
      pacemaker implantation (range: 3-120 months). We conclude that digital venography
      is a simple and relatively noninvasive method permitting better depiction of
      subclavian, anonymous and caval veins than Doppler US and also showing some
      vascular abnormalities which may complicate pacemaker implantation.

PMID- 9280938
TI  - [Combined conventional magnetic resonance, magnetic resonance angiography, and
      magnetic resonance cholangiopancreatography in the diagnosis and staging of
      pancreatic carcinoma].
AB  - PURPOSE: This study was aimed to integrating MR CholangioPancreatography (MRCP)
      and MR Angiography (MRA) to conventional MR images in the diagnosis and
      resectability assessment of pancreatic adenocarcinoma. MATERIAL AND METHODS:
      Twenty-three consecutive patients with pancreatic adenocarcinoma (16 in the head
      and 7 in the body-tail region) were examined with MR. Conventional MR, 3D MRCP
      and venous and arterial MRA images were acquired to assess biliary and vascular
      involvement. Acquisition time never exceeded 40-45 minutes. The images were
      independently studied by two radiologists and the final reading was decided upon
      consensus among readers. Sixteen patients underwent surgery. RESULTS: The
      diagnosis was confirmed at surgery in 16 patients and at percutaneous biopsy in
      7. Interreader agreement was considered high, with .83 interobserver variability.
      Pancreatic adenocarcinoma was found in all patients examined. Unresectability
      because of vascular involvement was correctly assessed in all patients but 1.
      Biliary obstruction was demonstrated in 13 patients, involving the biliary and
      pancreatic ducts in 9 and the biliary ducts only in 4. CONCLUSION: Technical
      advances now permit the extensive application of MRI to the study of abdominal
      conditions. The combination of MRI, MRCP and MRA can provide most of the
      information needed for the diagnosis and resectability assessment of pancreatic
      adenocarcinoma, which can otherwise be obtained only performing three different
      exams.

PMID- 9280939
TI  - [Choledocholithiasis: semeiotic and diagnostic accuracy of cholangiography with
      magnetic resonance].
AB  - The authors report their experience in the optimization of the diagnostic
      accuracy of Magnetic Resonance Cholangiography (MRC) to detect choledochal
      stones; pre- and post-MIP post-processing images were compared. Thirty patients
      with dilated biliary ducts (mean age: 55.6 years) were examined with MRC; two of
      them had stones in the intrahepatic biliary ducts. The gold standard and the
      inclusion criterion was ERCP. MRC was carried out with a 1.5 T superconductive
      magnet (Signa) with T2-weighted FAST SE sequences (TR/TE; 10000/256, matrix: 256
      x 128, slice thickness: 3 mm, TA: 6 min 28 s). Coronal MR images were blindly
      studied before and after MIP post-processing; Friedman's test was used for
      statistical analysis (p < .05). ERCP showed 92 cases of choledocholithiasis, with
      the stones ranging .2 to 3.4 cm; MRC before MIP post-processing had 97.1%
      diagnostic accuracy, 97.8% sensitivity and 95.8% specificity. These values are
      significantly different from those obtained after MIP (91.4%, 86.9% and 95.8%
      respectively). In our experience, pre- and post-MIP post-processing MRC can be
      considered a reliable and accurate noninvasive technique to detect choledochal
      stones.

PMID- 9280940
TI  - [Assessment of varicocele recurrence with ultrasonography, color and power
      Doppler].
AB  - To study the postoperative recurrences of varicocele and the relationship between
      recurrences and sperm variables, we reexamined postoperatively 48 patients aged
      14-56 years (mean: 25 years); the patients returned within a time range of 4 to
      36 months. All the patients underwent physical examination, B-mode, color and
      power Doppler sonography (US); the images were acquired with the patient both
      supine and upright, both at rest and during Valsalva maneuver. We studied the
      incidence of recurrences and their bilaterality, the presence of reflux with or
      without functional maneuvers, associated conditions, surgical complications and
      the improvement of sperm variables; color and power Doppler findings were
      compared. The incidence of recurrences (28) and that of major complications (2)
      were related to the type of surgery: thus, no complications but 26 recurrences
      were found in the patients with spermatic vein ligation, versus only 2
      recurrences but also 2 major complications (1 testicular ischemia and 1
      hydrocele) in the patients with ligation of the spermatic cord venous channels. A
      right varicocele was found in 12 patients, which confirmed the frequent
      bilaterality of this condition; 8 patients with recurrences had improved sperm
      variables and 6 presented associated conditions. Our trial confirms that B-mode
      US, combined with color and power Doppler, can show recurrences, bilaterality,
      surgical complications and associated conditions and emphasize the role of these
      exams in the postoperative follow-up of varicocele. However, no method alone,
      without the evaluation of sperm variables, permits to select the patients to be
      reoperated on.

PMID- 9280942
TI  - [Radiology information system project at the National Tumor Institute of Milan].

PMID- 9280943
TI  - [Embryo-fetal development in the early stages of pregnancy].
AB  - The introduction of high resolution transvaginal US in obstetrical clinical
      practice permits earlier and more detailed visualization of embryo-fetal
      structures in early pregnancy. A transvaginal US examination with a high
      resolution probe (5.0-6.0 MHz) was performed in 1246 pregnant patients between 9
      and 16 weeks of gestation and known gestational age. Ten embryo-fetal biometric
      parameters were measured (crown-rump length, biparietal diameter, head
      circumference, transverse cerebellar diameter, thoracic circumference, mean
      abdominal diameter, abdominal circumference, femur length, humerus length and
      foot length). Reference ranges with 5 degrees and 95 degrees percentile intervals
      were constructed for all biometric parameters in relation to gestational age.
      Only one scan per patient was considered for this study. All the parameters
      evaluated demonstrated a high correlation with gestational age at polynomial
      regression analysis. The mean coefficient of determination (r2) ranged from 97.15
      for biparietal diameter to 88.17 for transverse cerebellar diameter. The data are
      useful as reference range for the assessment of normal embryofetal development by
      transvaginal US in the early stages of pregnancy.

PMID- 9280941
TI  - [Embolization of iatrogenic renal vascular lesions with coaxial catheters and
      microcoils].
AB  - INTRODUCTION: We report our experience with the superselective embolization of
      iatrogenic vascular injuries. We used new coaxial catheters and new microcoils to
      assess their technical features and efficacy. MATERIALS AND METHODS: Diagnostic
      angiography by catheterization of the main renal artery was performed in 7
      patients with suspected renal vascular injury to detect injury presence and site.
      After super-selective catheterization of the feeding arteries with a coaxial
      catheter (Tracker 18), we performed embolization with platinum microcoils
      inserted using a coil pusher. The procedure efficacy was assessed at angiography
      and by comparing serum hemoglobin and hematocrit levels before and after
      embolization; posttreatment renal function was also studied. RESULTS: Selective
      embolization permitted complete occlusion of the arteries feeding the vascular
      injury in all patients, preserving as much parenchyma as possible. Hemoglobin and
      hematocrit levels were improved or unchanged after the maneuver (average
      hemoglobin level before embolization: 9.01 mg/dl versus 9.95 mg/dl after
      embolization; average hematocrit level before embolization: 27.3% versus 30.06%
      after embolization). We had no difficulty during microcoil insertion and the
      coaxial catheter was always stable. CONCLUSION: Superselective embolization of
      iatrogenic vascular injuries is an effective and definitive treatment. We
      recommend it in the patients with renal bleeding due to iatrogenic vascular
      injury after percutaneous diagnostic or therapeutic procedures.

PMID- 9280944
TI  - [Diagnostic accuracy of teleradiology in thoracic and abdominal diseases].
AB  - For one year now, teleradiology has linked the "S. Marcello" Hospital to the
      Department of Radiology of "Del Ceppo." Hospital in Pistoia, 30 kilometers away.
      Plain films are digitized (Lumiscan 50, Philips), transmitted over a dedicated
      standard telephone line and displayed at 1024 x 1024 x 8 bits. To study the
      diagnostic accuracy of teleradiology in chest and abdominal conditions, we
      digitized and transmitted to the Pistoia Dept. of Radiology, a sample of 156 (96
      chest and 60 abdominal) emergency examinations made in "S. Marcello" Hospital
      from January through November, 1995. The patients were 81 women (mean age: 69
      years) and 75 men (mean age: 66 years); the age range was 17-93 years. Three
      radiologists independently reviewed the images in the Pistoia Dept. of Radiology
      on a digital workstation enabled to manipulate images. They filled in some given
      forms specific for chest and abdominal radiography, which were compared with the
      same forms filled in by the radiologist in "S. Marcello" Hospital who reviewed
      plain films. The differences were never clinically important; they concerned
      emphysema (4 false positives and 2 false negatives), congestion of the hila (2
      false positives and 2 false negatives) and abnormal air in small bowel and colon
      (2 false positives and 2 false negatives). We believe these differences to be
      related to interobserver variability. The diagnostic accuracy of monitor image
      interpretation by the three radiologists who reviewed digitized radiographs
      exceeded 96% for both chest and abdominal examinations, which figure compares
      with literature data on high resolution workstations.

PMID- 9280946
TI  - [Comparison between measured and computed absorbed dose values in the tangential
      treatment of the breast].
AB  - The calculated absorbed dose values to the reference point of the breast
      tangential irradiation, obtained by 2-dimensional (2D) Treatment Planning Systems
      (TPS), were compared with the measured absorbed dose values obtained with a
      ionization chamber in an anthropomorphic phantom treated with two opposed photon
      beams of 60Co, 6 MV and 10 MV. This comparison was aimed at assessing the 2D
      algorithm dose overestimation due to the effect of missing tissue in the
      irradiated field. The ratio between the computed dose, Dc, and the measured dose,
      Dm, reached 1.08 for 60Co beams and 1.04 for X-ray beams of linacs. The Clarkson
      method gives an adequate correction factor for the calculated absorbed dose value
      in the reference point. The portal films of some patients were studied to
      estimate the correction factor for the treatment time or monitor units evaluated
      by TPS using tomographic breast central plane. The values of the correction
      factors reached 1.10 for 60Co photon beams and 1.04 for X-ray beams. The
      measurements were carried out with TLDs positioned in the central plane of the
      breast, covered by a special bolus, of a second anthropomorphic phantom. The dose
      homogeneity as well as the accuracy of the relative computed dose values in the
      breast phantom irradiated with 10 MV X-ray beams were assessed.

PMID- 9280945
TI  - [Factors affecting the contralateral dose for the non-treated breast in
      irradiation following quadrantectomy].
AB  - We evaluated, with a treatment planning system, the maximum and the mean
      contralateral breast doses, and, with thermoluminescent dosemeters LiF100; the
      skin dose during radiation therapy after conservative surgery. The doses were
      correlated with technical parameters through statistical analysis. Since 1995,
      100 patients have been considered, all of them treated with two 60Co tangential
      beams after quadrantectomy. The mean dose to the contralateral breast exhibited a
      statistically significant correlation with the gantry angle of the lateral
      (Pearson, p < .02) and medial beams (p < .01); the maximum dose was correlated
      with the gantry angle of the lateral (p < .002) and the medial beams (p < .002).
      In the last 50 patients, the skin dose (measured with TLDs) was correlated with:
      distance from beam edge (Pearson, p < .02), breast thickness (p < .01), gantry
      angle of the lateral beam (p < .005), gantry angle of the medial beam (p < .002).
      Furthermore, only the gantry angle of the lateral (p < .02) and of the medial
      beams (p < .01) exhibited statistically significant Spearman's correlation with
      skin dose. Wilcoxon's signed rank sum test for paired data was performed to study
      wedge dependence. The average contralateral breast dose using two wedges was
      statistically reduced with respect to the dose without wedges (p < .02). These
      results suggest that the dose to the contralateral breast could be significantly
      decreased by careful attention to the treatment details, which implies that the
      procedures related to the technical aspects of the therapy should be submitted to
      careful quality control.

PMID- 9280948
TI  - [Computerized tomography imaging of the infraorbital canal on the axial plane].

PMID- 9280947
TI  - [Intracavitary brachytherapy in esophageal neoplasms. Experience at the Radiology
      Institute of Brescia].
AB  - We investigated the role of brachytherapy in the management of esophageal cancer.
      From March, 1990, to December 1994, seventy patients, with biopsy-proved
      esophageal carcinoma, were treated with brachytherapy +/- external beam
      radiotherapy. According to the TNM staging system, 24 patients were graded as T1,
      24 as T2, 10 as T3, 9 as T4, and 3 as Tx. Median Karnofsky score was 80.
      Dysphagia was the major symptom in 68% of cases. Treatment consisted of low dose
      rate first, and then high dose rate brachytherapy, with progressive optimization
      of doses and fractions, up to total doses of 15-30 Gy in low dose rate and 7-21
      Gy in high dose rate. When associated, external beam radiotherapy was delivered
      with conventional schedules. Tolerance to treatment was good with slight acute
      toxicity. Symptoms were markedly improved, with reduction of dysphagia in 100% of
      cases. Overall survival was 75%, 47%, 23% and 18% at 6, 12, 24, 36 months; no
      significant difference was found between low and high dose rate groups.
      Furthermore, no difference was shown in the overall survival of the group treated
      with brachytherapy alone and the one with associated external beam radiotherapy.
      Late toxicity occurred in 10% of patients and was managed by endoscopic
      procedures in all cases. In our opinion, brachytherapy appears to be an effective
      palliative treatment; its role as radical treatment remains to be defined.

PMID- 9280950
TI  - [Hemorrhage secondary to developmental cerebral venous anomaly. A case report].

PMID- 9280949
TI  - [Magnetic resonance imaging of a case of spontaneous resolution of syringomyelia
      associated with type I Chiari malformation].

PMID- 9280951
TI  - [Traumatic lens dislocation. Magnetic resonance imaging of 2 cases].

PMID- 9280952
TI  - [Neurinoma of the vagus nerve in the parapharyngeal space. Magnetic resonance and
      magnetic resonance angiography of a case].

PMID- 9280953
TI  - [Rhabdomyosarcoma of the middle ear. Report of a case].

PMID- 9280954
TI  - [Pseudoaneurysm of the lingual artery. Report of a case treated with
      embolization].

PMID- 9280955
TI  - [Mammographic and echographic findings in a case of bifocal fat necrosis of the
      breast].

PMID- 9280956
TI  - [Agenesis of the right pulmonary artery. Magnetic resonance and computerized
      tomography features of a case].

PMID- 9280957
TI  - [Unusual case of pulmonary artery compression caused by aortic arch aneurysm].

PMID- 9280958
TI  - [The phenomenon of corrugated arteries. Report of 3 cases].

PMID- 9280959
TI  - [Description of an unusual case of hepatic leishmaniasis in AIDS].

PMID- 9280960
TI  - [Apparent double echogenicity of the splenic parenchyma: a sign of perisplenic
      elongation of the left hepatic lobe. Report of 3 cases].

PMID- 9280962
TI  - [New perspectives in obesity].

PMID- 9280961
TI  - [Pancreas divisum: demonstration of a case with cholangiopancreatography with
      magnetic resonance].

PMID- 9280963
TI  - [Replacement treatment of chronic renal insufficiency. Current perspectives].

PMID- 9280965
TI  - [Hemorrhagic complications and thrombotic phenomena in oral anticoagulation of
      elderly patients].
AB  - OBJECTIVE: To retrospectively analyze the hemorrhagic complications and
      thrombotic events associated with aging and the degree of anticoagulation in a
      series of ambulatory patients treated with acenocumarol and controlled in a
      specialized anticoagulant therapy unit. PATIENTS AND METHODS: A total of 1,613
      ambulatory patients were studied. Patients were divided into two groups (group 1,
      645 patients > 65 years old, mean age 71.7 +/- 4.5 years; INR, 2.1-2.8; group 2,
      968 patients < or = 65 years, mean age 53.7 +/- 10 years; INR, 2.8-4.2) for a
      time period of twelve months. The prevalence of hemorrhagic complications and
      severity according to a validated international index (Bleeding Severity Index),
      as well as the thrombotic events occurred despite anticoagulation therapy.
      RESULTS: Fifty-two hemorrhagic events (8/100 patients-year) were recorded in the
      older group (group 1). Twenty-six cases were considered banal episodes, 24 minor
      hemorrhages and two major hemorrhages. Ten patients (1.5/100 patients-year) had
      thrombotic complications. In the younger group (group 2) 150 bleeding episodes
      were recorded (15 patients-year), of which 11 were banal, 39 minor hemorrhages
      and no major hemorrhages. Only eight patients 0.8/100 patients-year) had
      thrombosis. The presence of local factors predisposing to bleeding was more
      common in group 1 (p < 0.001). Older patients had in general more complications
      than younger patients (p < 0.001), but no significant differences were observed
      between the occurrence of hemorrhages or thrombosis independently analyzed
      between both groups. The rate in the therapeutic range was greater among the
      youngest individuals (p < 0.05). CONCLUSIONS: Our results support the idea that
      patients with advanced age can benefit from a less aggressive anticoagulation. A
      statistical trend was observed, although not significant, towards the presence of
      major hemorrhages and thrombosis in this group of patients. The presence of local
      or predisposing factors to hemorrhage (underlying disease and NSAIDs use) is more
      relevant in patients with advanced age.

PMID- 9280964
TI  - [Pravastatin increases the activity pf the LDL receptors in lymphocytes of
      individuals with heterozygous familial hypercholesterolemia].
AB  - An investigation was conducted on the effects of pravastatin, an inhibitor of the
      HMG CoA reductase, on lipoproteins concentrations and degradation of LDL (low
      density lipoproteins) in 14 patients with familial hypercholesterolemia (FH).
      Therapy with pravastatin for twelve weeks, 20 mg every 12 hours, and a low fat
      (30% calories) and cholesterol (less than 300 mg/daily) diet decreased serum
      concentrations of LDL cholesterol and apolipoprotein B by 35.5% and 24%,
      respectively (p < 0.001 for both parameters). On the other hand, apolipoprotein A
      1 concentrations increased by 15.1% (p < 0.05) and HDL cholesterol (high density
      lipoproteins) by 6.8%; concentrations of apolipoprotein A-II did not change. LDL
      degradation in peripheral lymphocytes increased by 41.3% (p < 0.05) and a
      correlation was observed (p < 0.05) between percentage of LDL degradation and
      percentage in the LDL cholesterol decrease. Likewise, a positive trend (p =
      0.057) was observed between increases in LDL degradation and aging. These
      findings indicate that pravastatin favorably influences the lipoprotein profile
      and that this effect is mediated, at least partly, by an increase in cellular
      capacity of LDL degradation.

PMID- 9280966
TI  - [Clinical expression of systemic lupus erythematosus with anti-U1-RNP and anti-Sm
      antibodies].
AB  - The frequency of anti-U1-RNP and anti-Sm antibodies in systemic lupus
      erythematosus (SLE) varies according to the technique used for their detection.
      OBJECTIVE: To study the clinical manifestations associated with anti-U1-RNP and
      anti-Sm antibodies identified by different techniques. METHODS: 112 patients
      diagnosed with SLE were studied. Anti-U1-RNP and anti-Sm antibodies were detected
      by ELISA with a mixture of recombinant antigens, antigens obtained by
      immunoaffinity and by immunoblotting and counterimmunoelectrophoresis (CIE) with
      a saline extract of rabbit thymus. RESULTS: Anti-U1-RNP antibodies were detected
      in 70 (62.5%), 37 (33%) and 16 (14.2%) patients, and anti-Sm antibodies in 43
      (38.3%), 36 (32.1%) and 10 (8.9%) patients by ELISA, immunoblotting, and CIE,
      respectively. Anti-U1-RNP antibodies are associated with edema in the dorsal hand
      region, sclerodactylia, Raynaud phenomenon and pericarditis (CIE); arthritis,
      hand edema, Raynaud phenomenon and sclerodactylia (anti-70 KD-U1-RNP and anti-A
      U1-RNP by immunoblotting); and a lower incidence of discoid lupus and chronic
      renal insufficiency by lupus renal disease (ELISA). Anti-Sm antibodies are
      associated with Raynaud phenomenon and renal disease (CIE); cutaneous vasculitis,
      Raynaud phenomenon and thrombosis (anti-BB'-Sm immunoblotting); and arthritis and
      lower incidence of chronic renal insufficiency (ELISA). CONCLUSIONS: Anti-U1-RNP
      and anti-Sm antibodies detected by ELISA do not have the same clinical
      significance than those detected by immunoblotting or CIE. The clinical
      manifestations associated with such antibodies in the same SLE population vary
      according to the detection technique used.

PMID- 9280967
TI  - [Detection of cognitive deterioration in elderly patients attending an emergency
      hospital service].
AB  - BACKGROUND: An increasing proportion of patients attended at hospital emergence
      departments (HED) are elderly people. OBJECTIVES: a) To check the reliability of
      the usual medical assessment to detect the cognitive deterioration in elderly
      people attended at HED, compared with that performed systematically by means of
      an evaluation test of cognitive functions; b) to study the applicability of such
      a test in HED, on the basis of the time necessary for its administration, and c)
      to describe the deterioration prevalence in that group of patients and identify
      the possible associated risks for its detection in patients. PATIENTS AND
      METHODS: Prospective study including patients aged > or = 60 years attended at a
      HED, using the orientation, memory and concentration test (OMC) to perform the
      cognitive assessment. RESULTS: A total of 352 patients who had no exclusion
      criteria out of the 536 attended during the study period were included. Cognitive
      deterioration was not detected in 111 patients (31.5%); it was mild in 147
      (41.8%), moderate in 71 (20.2%) and severe in 23 (6.5%). In patients with
      moderate-severe deterioration according to the OMC test, such a deterioration was
      detected by the usual medical evaluation in 7% of cases. The mean time in
      completing the test was 2.6 +/- 0.9 minutes. An age > or = 80 years was
      associated with an increased relative risk for detecting moderate-severe
      cognitive deterioration (1.98; 95% CI, 1.42-2.78; p < 0.001), whereas the
      discharge diagnosis of respiratory disease was associated with a decrease of the
      relative risk (0.41; 95% CI, 0.19-0.89; p < 0.05). No association was observed
      with other factors, such as gender, home residence or final destination from the
      emergency department. CONCLUSIONS: The prevalence of cognitive deterioration in
      elderly people attended at HED is high and increases with age. The OMC test can
      be administered at HED to detect cognitive deterioration, which is not frequently
      detected by the usual medical assessment.

PMID- 9280969
TI  - [Epileptic crisis and cerebral vascular disease].

PMID- 9280968
TI  - [Clinical and evolutive study of plasma cell leukemia. Apropos of 9 cases].
AB  - Nine patients were diagnosed with plasma cell leukemia (PCL) from 1982-1995 at
      our hospital. Seven patients had primary PCL and the other two patients a
      secondary from. In this study the clinical and analytical features are reported,
      as well as the therapy and response obtained in these patients. Also, the
      karyotype findings in bone marrow of four of these patients are reported. At
      diagnosis, the most common symptom was bone pain which was associated with
      osteolytic lesions or diffuse bone demineralization. Analytical features were
      similar to those reported in other series of patients with PCL. Different
      therapeutical regimens were used, and VAD was the most commonly employed. Two
      patients underwent consolidation therapy with autologous transplantation of
      hemopoietic stem cells. The mean survival time was 5.5 months. Although PCL
      prognosis associated with chemotherapy is still poor, myeloablative therapy with
      hemopoietic support can increase the survival length in these patients.

PMID- 9280970
TI  - [Advances in the pathogeny of obesity: the physiology of leptin].

PMID- 9280971
TI  - [Alpha blockers in the treatment of benign hyperplasia of the prostate].

PMID- 9280972
TI  - [Dorsalgia in a young man].

PMID- 9280973
TI  - [28-year-old woman with multiple intracranial lesions].

PMID- 9280974
TI  - [Pain in the groin of a young female sportsman].

PMID- 9280975
TI  - [Progressive dyspnea in a patient with a preceding carcinoma of the breast].

PMID- 9280976
TI  - [A 45-year-old patient with fever of unknown origin].

PMID- 9280977
TI  - [MALT-type thyroid lymphoma].

PMID- 9280978
TI  - [Cholangitis with hepatosplenomegaly caused by Xanthomonas maltophilia in a
      patient with AIDS].

PMID- 9280979
TI  - [Polycythemia in a patient with HIV].

PMID- 9280980
TI  - [Benign peritoneal multicystic mesothelioma as a cause of ascites].

PMID- 9280981
TI  - [Monoclonal gammapathy of uncertain significance].

PMID- 9280982
TI  - [Inaugural conference given on the occasion of the Revue d'Epidemiologie et de
      Sante Publique 20th anniversary on the theme: how does a disease become a public
      health problem?].

PMID- 9280983
TI  - [Morbidity estimates of beneficiaries of national health insurance for seven
      chronic conditions].
AB  - This work is aimed at providing improved coefficients applicable to the
      statistics of Health Insurance concerning the long-lasting conditions in order to
      assess morbidity of Health Insurance members concerning diseases invoked
      legislation on long-lasting conditions. To reach this objective, we have applied
      the consequences of successive equivalence (between diseases and their specific
      treatment, and between the use of special prescriptions for exempting diseases
      and the acknowledgment of long-lasting conditions by Health Insurance) to the
      results of a survey on medicines carried out by the Caisse Nationale d'Assurance
      Maladie des Travailleurs Salaries in 1993 on the basis of a representative
      sample. Improved coefficients were equal to the inverse of the proportion of
      special prescriptions within the whole of the prescriptions including specific
      treatment. Those coefficients and their confidence intervals have been calculated
      for seven affections: non-insulin dependent diabetes [1.56-1.67], coronary
      disease [1.51-1.61], Parkinson's disease [1.51-1.85], manic-depressive psychosis
      [1.49-1.89], haemorrhagic rectocolitis and Crohn's disease [1.49-2.04], insulin
      dependent diabetes [1.10-1.20] and tuberculosis [1.61-3.33]. The critical
      analysis of our work and its comparison with the rare literature on the same
      subject confirms the value of our results. The application of those improved
      coefficients to the figures of prevalence and incidence provided by Health
      Insurance makes it possible to set confidence bounds to the statistics of
      morbidity concerning the people who are affiliated to that system of Health
      Insurance and treated for these diseases however serious they are.

PMID- 9280984
TI  - [Predictive factors for institutionalization in the context of geriatric planning
      in the Gironde department (France)].
AB  - The objective of this study was to investigate the predictive factors over five
      years follow-up of institutionalization, relevant for starting interventions in
      the area of Gironde (South Western France). This study deals with a longitudinal
      study of community residents aged 65 years and older. Of the 2792 subjects
      initially included in the cohort in year 1988, 2493 were selected for this study,
      leading to the subjects whose type of housing was known at least once over the
      five year follow-up (1989-1993). The statistical analysis was made with a
      discrete Cox proportional hazard model. Of the 2493 subjects, 150 entered an
      institution during the five years of follow-up, leading to a cumulative incidence
      of 7.1%. In the multivariate analysis, the predictive factors found in this study
      were age, absence of phone in the house, living in home for the aged, cognitive
      decline evaluated with the Mini-Mental-Status-Examination (MMSE), dependency for
      one item of the Lawton's scale (Instrumental Activities of Daily Living or
      IADLs), namely the inability to do shopping, and limited social contact with the
      family. These different indicators are a basis for decision making to target home
      care services fitted to the needs of the area.

PMID- 9280985
TI  - [Infant mortality trends compared with trends in handicapped children in Isere,
      1976-1985].
AB  - Since 1960 progress in obstetric and neonatology modified the survival chance of
      babies and the pattern of mortality causes. With the information available in the
      death certificates the aim was to analyse the trends in infant mortality for all
      0-1 year children deaths occurring from 1976 to 1991, and to look at its
      influence on disabled children prevalence rates. The study was conducted in Isere
      (France) and include 1702 infant deaths. A part from death groups with perinatal
      disease and/or with congenital defects, a group of deaths with risk factor of
      disability was identified. This group represented 43% of all the infantile deaths
      and showed a significant decreasing trend, very similar to the decrease of the
      early neonatal mortality component (until 1983). However, during the same period,
      for the disabled children prevalence and for the other infant mortality
      components, no significant variation was found. The decrease of the deaths with
      risk factor of disability suggests some influence on the disabled children
      prevalence.

PMID- 9280986
TI  - [Association between air pollen concentrations and seasonal allergies: synthesis
      of epidemiological studies published between 1978 and 1995].
AB  - Many clinical studies have shown a causal link between exposure to pollens and
      clinical symptoms of atopy. However knowledge regarding the dose-response
      relationship between airborne pollen counts and the occurrence of clinical
      symptoms of seasonal pollinosis in the population, are not well known. The review
      of epidemiological studies published in this field for the last 15 years
      indicates that most epidemiological studies were carried out using a panel study
      design of well documented pollinosis subjects. These studies aim at estimating
      the correlation between daily airborne pollen counts measured by an aeropollinic
      surveillance network and clinical indicators characterising the health condition
      of the studied population. Nevertheless, because of many methodological
      weaknesses, especially regarding the methods of statistical analysis, the results
      of these studies do not allow to conclude that there is a short term association
      between airborne pollen counts and the incidence of symptoms of seasonal
      pollinosis. This field of research is a priority in order to assess the public
      health impact of pollens, and to use with efficacy the data collected by
      monitoring networks.

PMID- 9280987
TI  - [Use of a logistic regression model at two levels in the analysis of medical
      practice variations: the prophylactic cesarean].
AB  - We show the use of a hierarchical logistic model to study the variations of the
      prophylactic cesarean section rate between the maternity hospitals of the Rhone
      Alpes region. These variations are analyzed according to the women
      characteristics at first level, and the maternity hospital characteristics at
      second level. We present the two-level hierarchical logistic model and the method
      of estimation of the fixed and random parameters. Then, we compare and discuss
      the results obtained with those of the usual logistic model. The usual logistic
      model underestimates the standard error of the regression parameters. In our
      example however, the results obtained with the hierarchical model do not modify
      the conclusions concerning the effect of the women characteristics. All the women
      characteristics increase significantly the probability for a woman to have a
      prophylactic cesarean section. Nevertheless, the hierarchical model reveals the
      effect of the maternity hospital characteristics and shows that the maternity
      hospitals which receive many "at risk" women tend to perform fewer prophylactic
      cesarean sections than the others, in women with the same characteristics. It
      permits to estimate the residual variance of second level linked to the
      unobserved characteristics of the maternity hospitals. It permits to show that
      the effect of the main characteristics of the women (previous cesarean section,
      dystocia, chronic fetal distress) vary between maternity hospitals.

PMID- 9280988
TI  - [Linking of individual data. Methods of linkage].
AB  - This paper gives an overview of linking methods of personal data computed in
      different files as registers and administrative or medical records.
      Epidemiological and demographic examples are studied, then the successive steps
      of record linkage are described:definition and choice of identifiants, searching
      and comparing pairs of records to determine whether they should be linked. A
      special mention is made to probability matching and methods optimizing the
      matching procedures. The discussion envisages the advantages of record
      linkage:better use of health statistics, new types of epidemiologic studies. The
      ethical problems and the need for evaluation are also discussed.

PMID- 9280989
TI  - [Cancer incidence in Mauritius (1989-1993)].

PMID- 9280990
TI  - [One year follow-up of methadone maintenance patients].

PMID- 9280991
TI  - [Women's health].

PMID- 9280993
TI  - [Anesthesia with low flow of fresh gases and closed circuit].

PMID- 9280992
TI  - [Socioeconomic categories and mortality].

PMID- 9280994
TI  - [Respiratory changes during laparoscopic cholecystectomy. A comparative study of
      three techniques].
AB  - OBJECTIVES: To analyze the repercussions of CO2 pneumoperitoneum on the
      ventilation of healthy patients undergoing laparoscopic cholecystectomy; to
      assess the influence of anesthetic technique and determine whether duration of
      procedure or CO2 volume are relevant factors. PATIENTS AND METHOD: Prospective
      study of 132 patients undergoing laparoscopic cholecystectomy. The patients were
      selected based on disease and level of anesthetic risk and then randomly assigned
      to three groups to receive anesthesia with oxygen/nitrous oxide (group I),
      isoflurane in O2 and air (FIO2 0.4) (group II) or propofol in continuous infusion
      with O2 and air (FIO2 0.4) (group III). Analgesia and muscle relaxation were the
      same in all groups. Monitoring included blood pressure (BP), heart rate (HR),
      electrocardiography (ECG), central venous pressure (CVP), capnography (PETco2),
      pulse oximetry (SaO2), peak airways pressure (PAP), FIO2, intra-abdominal
      pressure (IAP), volume in insufflated CO2 and serial gasometry. Readings were
      taken before pneumoperitoneum after 20 minutes and every 30 minutes until end of
      surgery. After surgery parameters were recorded four more times at intervals of
      30 minutes. RESULTS: The groups were homogeneous. pneumoperitoneum caused a
      decrease in PaO2 (p < 0.001) and SaO2 and increases in PaCO2, PETco2 and CVP,
      although levels later stabilized. No relation was found between duration of
      pneumoperitoneum or CO2 volumen and any of the changes observed. Group I had the
      lowest mean PaO2 before pneumoperitoneum and 60 minutes later (p < 0.05). Group
      II had the smallest increase in PaCO2, although the difference was non
      significant. CONCLUSIONS: CO2 pneumoperitoneum caused ventilatory changes
      dependent on uptake and increased abdominal pressure. The duration and volume of
      CO2 used did not influence the parameters studied. The clinical significance of
      these changes is slight in the healthy patient. The anesthetic agents used did
      not have substantial effects.

PMID- 9280995
TI  - [Postoperative analgesia with epidural methadone in patients operated for hernia
      of the lumbar disc].
AB  - OBJECTIVES: To determine whether the direct application of a single dose of
      methadone on the dura mater at the end of surgery to repair a lumbar disk hernia
      provides effective analgesia over the next 24 hours. PATIENTS AND METHODS: We
      conducted a randomized double blind study in 40 ASA I patients undergoing
      elective herniated disk repair under general anesthesia. The sample was divided
      into two groups (A and B). Group A patients received a solution of methadone in
      saline solution (5 mg methadone/5 ml saline) applied to the dura before the end
      of surgery. Group B patients (controls) received only 5 ml of saline. Pain
      intensity was assessed on a visual analog scale (VAS) during the postoperative
      period. Also recorded were the observer's impression and the amount of analgesia
      (ketorolac) consumed through a system providing patient controlled analgesia.
      RESULTS: Each group contained 20 patients. Group A patients needed significantly
      less postoperative analgesia (64.2 +/- 14.3 mg) than group B patients (109.6 +/-
      16.5 mg). The VAS scores were significantly lower in group A during the first two
      hours after surgery and were correlated with the observer's impression. No
      patients suffered serious complications during the study. CONCLUSIONS: Topical
      administration of 5 mg of methadone on the dura mater at the end of herniated
      lumbar disk repair is an easy, safe and effective technique for providing
      postoperative analgesia.

PMID- 9280996
TI  - [Quantification of dehydration of soda lime in clinical circumstances].
AB  - HYPOTHESIS AND OBJECTIVES: When the CO2 absorbents, soda lime and baralime, have
      lost their normal level of hydration, they may react with certain halogenated
      anesthetics to produce appreciable levels of carbon monoxide. The degree of
      absorbent desiccation has been considered the limiting factor for this
      phenomenon. This study quantifies the level of dehydration of lime produced under
      clinical conditions and the influence of several factors. MATERIAL AND METHOD:
      Desiccation was determined: 1) at set periods of time (3, 7 and 14 days) after
      clinical use of fresh soda lime in general anesthesia using a fresh gas flow
      (FGF) of 6 l/min, and 2) after gas had been crossing the continuous flow (CF)
      oxygen reservoir at 7 l/min for 17 and 65 hours. Two anesthetic systems were
      used: a) the Ohmeda Excel-210, in which the continuous FGF did not cross the
      reservoir and b) the Siemens Ventilator 710, in which the FGF did cross the
      reservoir. The experiments were repeated with three types of lime. RESULTS: The
      clinical use of lime for 3, 7 and 14 days caused different levels of desiccation,
      with decreases in hydration of up to 50% and 14 days. Nevertheless, water content
      was always over 5%, a level at which no reaction with halogenated agents takes
      place. After 17 and 65 hours of CF in the circuit where continuous FGF did not
      pass through the canister, the water content did not change. With the Siemens 710
      circuit, in which the continuous FGF crossed the canister, the dehydration level
      was 1.2 +/- 0.3% after 17 hours and 0.7 +/- 0.3% after 65 hours, a level that can
      produce CO upon reaction between lime and halogenated gases. The type of lime
      used had little effect. CONCLUSIONS: Lime does not desiccate to levels able to
      produce CO in daily use, regardless of the FGF system used. The phenomenon of
      desiccation depends on two factors: 1) use of anesthetic equipment in which
      continuous FGF conditions require gas to pass through the canister, and 2) the
      maintenance of CF for a sufficient period of time.

PMID- 9280997
TI  - [Postoperative cognitive dysfunction].
AB  - Although postoperative behavioral anomalies were first reported more than one
      hundred years ago, only in the past ten years has the profile for postoperative
      cognitive dysfunction (POCD) been defined. POCD is reversible and it has been
      suggested that the disorder has implications for increased mortality and
      morbidity if it is not diagnosed and treated early. At present the clinical
      presentation of POCD is thought to be variable and fluctuating, ranging from
      slight disorientation to coma. POCD can develop soon after surgery or appear
      several days later and its incidence is unknown as a result of the methodological
      difficulties involved in studying this entity. Of the various etiological factors
      that have been named, many can be modified during the period surrounding surgery.
      Once symptoms have developed,whether in the recovery unit or later, it is
      important to eliminate organic factors and begin treating the cause. The most
      important drugs for treatment are neuroleptics and benzodiazepines. We review the
      definition, epidemiology, etiology, pathophysiology and treatment of POCD and
      include a list of diseases and drugs associated with its development, as well as
      a description of psychological tests used for diagnosis.

PMID- 9280998
TI  - [Late ischemia and carpal tunnel syndrome secondary to catheterization of the
      radial artery].
AB  - Invasive measurement of blood pressure has many advantages. Although arterial
      canalization is a low-risk technique of great benefit to the patient,
      complications must be looked for. We report the case of a man who underwent
      triple coronary bypass with arterial canalization requiring several punctures to
      achieve. Two weeks after the procedure the patient showed signs of hand ischemia
      and acute carpal tunnel syndrome, which evolved favorably after treatment with
      heparin sodium and prostaglandin E1. We emphasize the importance of an earlier
      wrist fracture as the predisposing factor for both conditions and the need to
      examine collateral circulation in the hand and look for carpal tunnel syndrome
      before canalization.

PMID- 9281000
TI  - [Obstruction with a flexometallic light tube: an unexpected complication].

PMID- 9280999
TI  - [Subarachnoid anesthesia with minimal doses of lidocaine in ambulatory
      arthroscopic surgery of the knee].
AB  - The objective is demonstrate that subarachnoid anesthesia with 2% isobaric
      lidocaine at low doses (0.5 mg/kg) is safe and effective for outpatient
      arthroscopic surgery of the knee. This was a prospective study of 150 ASA I-III
      patients undergoing arthroscopic knee surgery as outpatients under subarachnoid
      anesthesia. With no prior vascular filling, we provided blockade by administering
      2% isobaric lidocaine at a dose of 0.5 mg/kg through a Sprotte 25G needle without
      vasoconstrictor. We assessed effectiveness and degree of sensory-motor blockade,
      cardiovascular repercussions, recovery time (until reversal of blockade,
      ambulation, micturition and discharge) as well as side effects observed. The mean
      dose of lidocaine used was 33.44 +/- 4.16 mg. The sensory-motor blockade achieved
      provided optimum conditions for prevention of ischemia and the practice of the
      surgical procedure in all cases. Surgery lasted a mean 38 +/- 10 min. Hemodynamic
      changes were not clinically significant and no patients additional fluids,
      atropine or vasopressors. Time from start of blockade until ambulation,
      micturition and discharge from the recovery unit were 123 +/- 8.3, 175 +/- 12.4
      and 194 +/- 13.4 min, respectively. Micturition was spontaneous in all cases.
      Complications recorded were cephalea and backache. In conclusion, subarachnoid
      anesthesia at low doses of 2% isobaric lidocaine provides excellent conditions
      for practicing arthroscopic surgery of the knee on outpatients, with minimum side
      effects.

PMID- 9281001
TI  - [Fiberoptic bronchoscopy through a laryngeal mask].

PMID- 9281002
TI  - [The laryngeal mask in fiber optic bronchoscopy in pediatric therapy].

PMID- 9281003
TI  - [Combined intradural-epidural anesthesia in a case of Steinert's disease].

PMID- 9281004
TI  - [Fatty liver in pregnancy. Presentation of a case].

PMID- 9281005
TI  - [A neonate with a large cystic hygroma: management of the airway].

PMID- 9281006
TI  - [Practical clinical implications of megastudies for primary prevention].
AB  - The results of different meta-analyses conducted in primary prevention have shown
      an insignificant difference in total mortality or coronary heart disease (CHD)
      mortality; and only two studies have shown differences in the incidence of CHD.
      The WOS study, the first study in primary prevention done with statines, observed
      a 20% reduction in the total cholesterol, a relative risk reduction of 31%, an
      absolute risk reduction of 2.4% and the number of patients who needed to be
      treated, to prevent coronary disease during a five year period, was 42. Subgroup
      analyses showed a greater benefit for high risk patients: smokers and those with
      peripheral vascular disease. This is why the utilization of a cardiovascular risk
      estimation, instead of isolated cholesterol levels or other risk factors, is
      currently recommended. However, it is important to bear in mind that the results
      of the WOS study cannot be easily extrapolated to Spain because the rates of CHD
      are much lower here than the ones observed in Scotland. Promotion of treatment of
      high risk patients with statines must be accompained by a promotion of a healthy
      lifestyle at both the individual and the community level.

PMID- 9281007
TI  - [Beta-blockers in cardiac insufficiency: should they always be considered in the
      therapeutic strategy? Arguments in favor].
AB  - Congestive heart failure is an increasing cause of mortality among the aging
      population. The current management approaches have increased the survival of
      patients with congestive heart failure, although the mortality rate remains high.
      Thus, any effort to reduce mortality in this condition seems justified. Beta
      adrenergic blocking agents have shown to improve functional class and the
      ventricular function of heart failure patients; the use of these agents should be
      considered in congestive heart failure patients unless an increase in mortality
      with betablockers can be demonstrated. In fact, beta-blockers reduce mortality,
      as the recent study of carvedilol has demonstrated. Therefore, beta adrenergic
      blocking agents should be incorporated into the strategies of management of
      patients with congestive heart failure.

PMID- 9281008
TI  - [Beta-blockers in cardiac insufficiency: should they always be considered in the
      therapeutic strategy? Arguments against].
AB  - The evidence supporting the use of beta-adrenergic blockers in the treatment of
      heart failure secondary to systolic dysfunction is reviewed. Up to date, seven
      controlled trials of carvedilol in patients with heart failure have been
      published. It has been concluded that the use of the non-selective, third
      generation beta-adrenergic blockers, with alpha-adrenergic (vasodilator) and
      antioxidant properties, carvedilol, is only justified in patients with mild or
      moderate heart failure without contraindications to beta-adrenergic blockers.
      There are not data to support the use of carvedilol in patients with severe or
      unstable heart failure. It seems logical to wait for the results of the ongoing
      trials (BEST Trial, CIBIS II Trial, COMET Trial, and MERIT Trial) to more
      precisely define the role that beta-adrenergic blockers should play in the
      treatment of patients with heart failure. The information presently available
      suggests that carvedilol should be considered a therapeutic agent for the
      prevention of progressive clinical heart failure rather than for the treatment of
      refractory heart failure.

PMID- 9281009
TI  - [Tendencies in mortality from cardiovascular diseases in the Valencian community
      (1976-1992)].
AB  - INTRODUCTION AND OBJECTIVES: Age-adjusted cardiovascular mortality has
      experienced a sharp decrease in Spain and, also, in the Valencian Community since
      approximately the mid-seventies. The objective of the present study is to
      describe the evolution of mortality due to cardiovascular and cerebrovascular
      diseases in the Valencian Community and their provinces, during 1976-1992.
      MATERIAL AND METHODS: The annual series of raw, specific and age-standardized
      mortality rates have been constructed and analyzed for the Valencian Community
      and provinces, from 1976 to 1992, fitting subsequently Poisson regression models
      to the rates. RESULTS: There exists a significant descendent trend of
      cardiovascular mortality, with an even more marked decrease for cerebrovascular
      disease. Mortality rates are higher in the Valencian Community than in general
      population of Spain. There is a rise in mortality rates with the increase of age.
      The female gender has a significant protective effect. Valencia and Alicante
      present higher risks than Castellon. CONCLUSIONS: Cardiovascular mortality in the
      Valencian Community during the period 1976-1992 decreased in all age groups,
      especially for cerebrovascular mortality. A greater magnitude in the masculine
      rates is observed. Castellon is the province associated with the lowest risk of
      death by cardiovascular disease.

PMID- 9281010
TI  - [Long-term prognosis of patients with syncope of unknown origin in prolonged
      asystole induced by the head-up tilt test].
AB  - INTRODUCTION AND OBJECTIVES: Prognosis and therapeutic assessment of patients
      with syncope and prolonged asystole during head-up tilt test remain unclear. The
      aim of the present study was to analyze the clinical evolution of patients with
      syncope of unknown origin, no heart disease and severe cardioinhibitory response
      induced by head-up tilt. METHODS: A prospective follow-up study was performed in
      12 patients (6 male and 6 female, mean age 31 +/- 20 years) with recurrent
      syncope, no heart disease and affected by severe cardioinhibitory syncope induced
      by head-up tilt test. This was defined as syncope or near-syncope induced by
      baseline or isoproterenol tilt with asystole of > or = 3 seconds. All patients
      were re-tilted twice: with salt and fluid and with metoprolol (25 mg/b.i.d).
      According to the results of these tests, 5 patients were discharged with dietetic
      measures (salt & fluid) and 5 with metoprolol. In 2 patients who showed recurrent
      prolonged asystole a DDD pacemaker was implanted. RESULTS: After follow-up of 34
      +/- 20 months all patients ae alive. The number of recurrences was small (2
      syncopes and 2 near-syncopes). No relationship was observed between the number of
      syncopal recurrences and the applied treatment. CONCLUSIONS: We conclude that
      prolonged asystole induced by head-up tilt test does not confer an adverse
      prognosis in patients with syncope of unknown origin and no heart disease, thus,
      the clinical evolution of these patients is benign.

PMID- 9281011
TI  - [Evaluation of myocardial viability with technetium-99m isonitrile and thallium
      201. Results of a Spanish multicenter trial].
AB  - BACKGROUND: Regions with severe impaired function in patients with chronic
      coronary artery disease may have improved contractility after coronary
      revascularization procedures. This multicentric trial was undertaken to assess
      the yield of rest technetium-99-isobutil-isonitrile (99mTc-MIBI) and thallium-201
      (201Tl) single photon emission tomography in the prediction of functional
      recovery. PATIENTS AND METHODS: 116 patients (mean age 59 +/- 10, 12 women) with
      severe impairment of regional contractility who underwent coronary artery bypass
      grafting (n = 84) or percutaneous coronary angioplasty (n = 32) were studied.
      Rest 99mTc-MIBI and 201Tl single photon emission tomography and three views
      radionuclide ventriculography were performed before and 3-6 months after
      revascularization. Regional contractility and radiotracer uptake were evaluated
      in 9 left ventricular segments. RESULTS: No change was observed in mean left
      ventricular ejection fraction pre- and post-revascularization (41.1% +/- 14.5% vs
      41.8% +/- 15.7%). 28% of patients increased > 5 ejection fraction units, 50% did
      not change and in 22% of patients ejection fraction decreased > 5 units. Only
      34.4% of segments with severe impairment of regional contractility improved after
      revascularization. Using 30% uptake as the lower limit of myocardial viability,
      sensitivity of 79% and specificity of 40% for 99mTc-MIBI and 80% and 46%
      respectively for 201Tl were obtained. There was a significantly inverse relation
      (p = 0.04) between the number of segments with less than 30% of radiotracer
      uptake and the probability of increasing ejection fraction after
      revascularization. CONCLUSIONS: No differences were observed in the sensitivity
      or specificity of 99mTc-MIBI and 201Tl single photon emission tomography in the
      prediction of functional recovery after revascularization in patients with
      coronary artery disease and severe impairment of regional contractility. The
      probability of increased ejection fraction after revascularization is inversely
      related to the extent of the regions with less than 30% of uptake.

PMID- 9281012
TI  - [Angiographic correlation of ST segment depression in exercise test in precardial
      electrocardiography leads after inferior wall acute myocardial infarction].
AB  - OBJECTIVES: This study was aimed to establish the angiographic correlation of the
      exercise-induced ST segment depression in precordial leads after an uncomplicated
      inferior wall myocardial infarction. METHODS: We studied retrospectively 67
      patients with a recent inferior wall acute myocardial infarction who took an
      exercise stress test following Bruce protocol and a coronary angiography within 3
      months. Four groups were defined according to the ST segment response to
      exercise: group I, no ST segment changes; group II, ST depression in leads V1-V4;
      group III, ST depression in leads V5-V6; and group IV, ST depression in leads V1
      V6. RESULTS: There were no significant differences among the groups for clinical
      and exercise variables, except for age (groups I and II were significantly
      younger than groups III and IV). The prevalence of multivessel coronary artery
      disease (two- and three-vessel disease) was 21%, 18%, 52% and 72% for group I to
      IV respectively (p = 0.007). The prevalence for left anterior descending coronary
      artery disease was 5%, 9%, 35% and 50% for group I to IV respectively (p = 0.01).
      By multivariate logistic regression analysis, only age > 60 years (p = 0.002) and
      exercise group III and IV (p = 0.02) were independent predictors for the presence
      of multivessel coronary disease. Whereas an ST exercise response type I or II in
      a patient < or = 60 years virtually excluded the presence of multivessel disease
      (negative predictive value, 0.90), an ST exercise response type III or IV in a
      patient > 60 years strongly suggested the presence of multivessel disease
      (positive predictive value, 0.72). CONCLUSIONS: Age and exercise-response of ST
      segment in precordial leads are useful variables for predicting the presence or
      absence of multivessel coronary artery disease after an uncomplicated inferior
      wall acute myocardial infarction.

PMID- 9281013
TI  - [The significance of the elevation of basal and exercise segments on Q-leads
      after acute myocardial infarct].
AB  - INTRODUCTION: ST segment elevation on Q-leads has been related to a greater
      infarct size and to the existence of ventricular aneurysm. On the other hand, ST
      elevation during exercise testing has been related to the presence of myocardial
      viability. OBJECTIVES: In the present study we investigated the relation between
      ST segment elevation on infarct-related electrocardiographic leads at rest and
      during exercise with: a) the extension and severity of the regional dysfunction;
      b) the presence of myocardial viability (response to dobutamine), and c) the
      residual stenosis in the culprit artery. MATERIAL AND METHODS: The study group
      was composed of 51 patients; cardiac cathetherism (8 +/- 3 days) and exercise
      testing (8 +/- 2 days) were performed during the pre-discharge period. In
      contrast ventriculography (centerline method) we determined the circumferential
      extension (rads) and the severity (SD/rad) of the regional dysfunction at rest
      and after dobutamine (10 micrograms/kg/min). The minimal luminal diameter (MLD)
      in the culprit artery was also measured. Results are expressed as median [Q1-Q3]
      and the differences among the groups were assessed by Mann-Whitney U. RESULTS:
      Patients with ST segment elevation in two or more leads at rest (n = 36) showed a
      greater (41 [30-51] rads vs 20 [14-41] rads; p = 0.007) and more severe regional
      dysfunction (1.9 [1.5-2.5] SD/rad vs 0.6 [0.5-2.4] SD/rad; p = 0.01), less
      response to dobutamine (% of reduction of the dysfunction extension after
      dobutamine) (17 [0-42]% vs 50 [24-100]%; p = 0.004) and smaller MLD (0.5 [0-0.9]
      mm vs 0.8 [0.6-1.1] mm; p = 0.03). Likewise, patients with exercise-induced ST
      segment elevation (n = 28) showed less response to dobutamine (15 [0-45]% vs 40
      [21-57]%; p = 0.03) and smaller MLD (0.5 [0-0.7] mm vs 0.9 [0.5-1] mm; p = 0.02).
      There were non significant differences between patients with and without ST
      elevation during exercise in the extension or severity of the regional
      dysfunction. ST segment elevation both at rest (RR 0.2; CI 95% 0.04-0.85) and
      during exercise (RR 0.19; CI 95%: 0.05-0.69) decreased the probability of
      improvement with dobutamine. CONCLUSIONS: We conclude that ST segment elevation
      on Q-leads at rest is related to a more extended and severe dysfunction. Patients
      with ST segment elevation (at rest or during exercise) show less response to
      dobutamine (myocardial viability less likely) and a more severe residual coronary
      stenosis.

PMID- 9281015
TI  - [The use of transesophageal echocardiography in the diagnosis of aortic hematoma
      after an aortic recoarctation angioplasty].
AB  - Transesophageal echocardiography is a very useful technique in studying thoracic
      aorta diseases, particularly aortic dissection and aortic intramural hematoma. In
      this report, we describe a case of aortic intramural hematoma after balloon
      angioplasty of a recoarctation. This case illustrates the importance of
      transesophageal echocardiography in the diagnosis and subsequent management of
      possible complications following this technique.

PMID- 9281014
TI  - [Methods of investigation in clinical cardiology. VIII. Meta-analysis and
      systematic reviews in cardiology].
AB  - Over the last 20 years, the development of meta-analysis has been aimed at
      obtaining objective synthesis of the available results on specific research
      questions. The main achievements of meta-analysis include the application of
      techniques to perform systematic literature searches and to obtain unbiased
      selection of studies, data extraction and pooled estimates of effect. This paper
      discusses the methodologic steps to follow when conducting a meta-analysis, with
      emphasis on study selections, data collection and statistical methods to combine
      the results from individual studies. We also present a set of guided questions as
      an aid to critically evaluate the conclusions of published meta-analyses. The
      application of meta-analytic techniques to cardiology is illustrated using a meta
      analysis of the randomized controlled trials of angioplasty versus bypass surgery
      in the management of patients with ischemic heart disease.

PMID- 9281017
TI  - [Prosthetic endocarditis and splenic abscess caused by Clostridium
      clostridiformis].
AB  - We report the first case of Clostridium clostridiformis endocarditis in a 71 year
      old man with an aortic prosthetic valve. He was febrile with left upper quadrant
      pain and left lower lobe infiltrate in chest X ray. The diagnosis was made by
      gram-positive bacilli grown from three blood cultures. Transthoracic and
      transesophageal echocardiogram showed a paraaortic abscess. A computed
      tomographic scan of the abdomen revealed a large splenic abscess. He received
      penicillin G 4 million units every 4 hours intravenously. A successful
      percutaneous drainage guided computed tomographic scan was performed. The patient
      remained febrile and a new computed tomographic scan of the abdomen revealed
      residual splenic abscess. A splenectomy was performed. The patient defervesced on
      the second day of surgery and remained afebrile during the remainder of his
      hospitalization. He has returned for medical follow-up and two years later the
      patient is asymptomatic.

PMID- 9281016
TI  - [Heart transplantation in a patient with rheumatoid arthritis].
AB  - A 56 year-old woman with rheumatoid arthritis was diagnosed with idiopathic
      dilated cardiomyopathy. She developed progressive heart failure that was
      refractory to conventional medical management. Heart transplantation was
      performed bearing in mind the controversy that surrounds its use in patients with
      a systemic disease. Transplant and rheumatoid arthritis were favorable at 33
      month evolution. The immunosuppressive therapy required for the transplant helped
      the control of her articular disease.

PMID- 9281019
TI  - [Emergency medicine for the practitioner].

PMID- 9281018
TI  - [Occlusion of the left main coronary artery with silent ischemia and syncope].
AB  - Mortality in the total occlusion of the left main coronary artery is very high,
      and the few cases who lived reported were very ill and symptomatic patients. We
      present a case with angiographic documentation of total occlusion of the left
      main coronary artery in a patient without angina and with a normal rest
      electrocardiogram in which a syncope was the only symptom. Severe isolated silent
      ischemia was induced during an exercise test. Total occlusion of the left main
      coronary artery associated to silent myocardial ischemia without cardiac failure
      has never been previously reported.

PMID- 9281020
TI  - [Emergency medicine for the practitioner: abdominal pain].

PMID- 9281022
TI  - [Emergency medicine for the practitioner: fever at the end of a voyage].

PMID- 9281021
TI  - [Emergency medicine for the practitioner: coma and confusional states].

PMID- 9281023
TI  - [Emergency medicine for the practitioner: chest pains].

PMID- 9281025
TI  - [Emergency medicine for the practitioner: suicidal crisis].

PMID- 9281026
TI  - [Emergency medicine for the practitioner: neurological emergencies].

PMID- 9281024
TI  - [Emergency medicine for the practitioner: headaches].

PMID- 9281027
TI  - [Emergency medicine for the practitioner: emergencies in the alcoholic patient
      and the drug addict].

PMID- 9281028
TI  - [Emergency medicine for the practitioner: urological emergencies].

PMID- 9281029
TI  - [Emergency medicine for the practitioner: palpitations and cardiac arrhythmia].

PMID- 9281030
TI  - [Emergency medicine for the practitioner: shock].

PMID- 9281031
TI  - [Emergency medicine for the practitioner: management of patients who are victims
      of a smoky fire].

PMID- 9281032
TI  - [Role of endoluminal ultrasonography in the treatment of rectal carcinoma].
AB  - Endoluminal sonography is an excellent technique in preoperative staging of
      rectal carcinoma. This minimally invasive technology makes individual planning of
      therapy possible and is a very good tool in postoperative follow-up and
      documentation. In comparison with the techniques of CT and MRI it is less
      expensive and the mobile unit can easily be moved e.g. into the operating
      theatre. There are no contraindications for this examination, postoperative
      tissue scars and metal implants will not disturb the imaging. We think that
      endoluminal sonography will be able to facilitate individual decision making in
      the treatment of rectal carcinoma.

PMID- 9281033
TI  - [Small intestine transplantation].
AB  - Since the development of new immunosuppressive agents, as FK506, the results of
      small bowel transplantation have greatly improved. The patient survival at one
      year has increased from 25% during the cyclosporin era to 65% in 1995 and the
      graft survival from 19% to 57% respectively. Clearly, the postoperative
      complications are still frequent and severe and do not allow a wide
      generalisation of this method. However, total parental nutrition is not an
      appropriate solution for the long term management of patients with terminal
      intestinal insufficiency. In Switzerland, these patients survive for several
      years and finally die of problems that small bowel transplantation could already
      successfully overpass.

PMID- 9281035
TI  - [Bursitis of the iliopsoas bursa].

PMID- 9281034
TI  - [Colonic perforation due to fecaloma. Apropos of 3 case reports].

PMID- 9281036
TI  - [Solitary nodule of the thyroid: diagnostic tests and surgical treatment].

PMID- 9281037
TI  - [The virtues of grapes].

PMID- 9281038
TI  - [Professor Maurice Roch (1878-1967); in memoriam].

PMID- 9281039
TI  - [Re H. Duruz' article on injuries of the pelvis and femur (Vol 117, pp. 77-80,
      1997)].

PMID- 9281041
TI  - [Asthma induced by exercise].
AB  - Exercise induced-asthma (EIA) is a frequent symptom concerning about 12% of the
      general population and at least 90% of asthmatics. It is often the first
      manifestation of asthma and is underestimated both by the patient and the
      practitioner. The pathophysiological mechanism is dealing with thermodynamic
      changes of bronchial mucosa, however it is not completely elucidated. Rapid
      cooling of bronchial mucosa and rewarming of expired air induces bronchial hyper
      circulation, hyperosmolarity and mast cell infiltration with release of mediators
      responsible for the bronchial narrowing after exercise. The diagnosis of EIA is
      usually historical. The measurement of peak flow after the exercise is the
      easiest way to confirm the diagnostic. Provocation tests in laboratory are
      sometimes useful. Warm-up protocoles are insufficient to prevent EIA in athletes.
      The beta-2-mimetics are the first choice drugs and may be associated with
      nedocromil-cromolyn if necessary. Inhaled corticosteroids are effective in long
      term administration, but it is a treatment of third choice. When corticosteroids
      are necessary, "unstable" asthma should be suspected.

PMID- 9281040
TI  - [Exertional intolerance in respiratory insufficiency: principal mechanisms].

PMID- 9281043
TI  - [Lungs and underwater diving].

PMID- 9281044
TI  - [Assisted ventilation in chronic neuromuscular diseases. The Vincre Group].

PMID- 9281042
TI  - [Acute altitude pulmonary edema].

PMID- 9281045
TI  - [Osteopenia: a consequence of anorexia nervosa].
AB  - The bone density in the spine and femoral neck was measured by dual-energy X-ray
      absorptiometry in 24 female with anorexia nervosa 14 to 34 y.o. (20.6 +/- 5.5
      y.o.). Osteopenia or osteoporosis were always present. All the cases presented
      with hypogonadotrophic hypogonadism and secondary amenorrhea between 4 and 194
      months (40.6 +/- 53.8 months) and with low levels of oestradiol and
      gonadotrophins. The anorectic patient cumulates hypogonadism and a low intake of
      calories, calcium and vitamin D, which causes a low body mass index. These
      factors are more important when present before peak bone mass is reached. The
      gonadotrophic deficit in the young anorectic male is less obvious clinically than
      in the young female with amenorrhea but can be however documented with hormonal
      data. The osteopenia of the anorectic girl can be at least partially corrected
      with the hormonal and nutritional treatment. In order to reach an adequate peak
      bone mass in late adolescence or early adulthood and to prevent the development
      of osteopenia, the male and female anorectic patients should receive a hormonal
      substitution and an adequate nutritional supply of calcium and vitamin D, as soon
      as the diagnosis has been made.

PMID- 9281046
TI  - [Psychosomatic consequences of sexual abuse: a case of Bartter pseudo-syndrome in
      an anorexic patient].

PMID- 9281047
TI  - [Autotransfusion: reflections on the preparation prior to donation].

PMID- 9281048
TI  - [Criteria for choosing a hearing aid].

PMID- 9281049
TI  - [A look at neurology].

PMID- 9281050
TI  - [Quality assurance in the Psychogeriatric Day Hospital of Lausanne: the admission
      procedures].

PMID- 9281051
TI  - [Sects, sectarisms and authentic spiritual pathways: can we learn to discern
      between them in order to counsel?].

PMID- 9281052
TI  - [The dental doctor].

PMID- 9281053
TI  - [Pemphigus and pemphigoid. A review and case reports].

PMID- 9281055
TI  - [WHO: cooperation with other specialist organizations. Interview by Roger D.
      Weill].

PMID- 9281054
TI  - [Stomatology in private practice. A field study in the catchment area of the
      University of Bern].

PMID- 9281056
TI  - [A large dental study of recruits in Thun: a general staff exercise under
      Lieutenant Colonel Niklaus P. Lang].

PMID- 9281057
TI  - [Cysts in the maxillofacial and neck areas. The annual meeting of the Swiss
      Association for Oral Surgery and Mouth Diseases (SAKM) on 23 March 1996 in
      Lucerne].

PMID- 9281058
TI  - [The orodental health program of the World Health Organization].

PMID- 9281059
TI  - [Cerec--an undisputed success of tooth-color CAD/CIM esthetic restorations. The
      Scientific Cerec Symposium of 15/16 March in Zurich].

PMID- 9281060
TI  - [Length of gestation of Freiberger mares with mule and horse foals].
AB  - In a retrospective study the gestation lengths of two groups, each consisting of
      193 "Freiberger" mares, were compared. The mares of the first group were bred by
      a donkey, those of the second group by a stallion of the "Freiberger" breed. On
      average, the gestation length of mares with "Freiberger" foals lasted 336.5 days,
      and that of mares with mule foals 343.1 days. The difference between both groups
      was significant (p < 0.001). The shortest and longest observed gestation length
      of mares with "Freiberger" foals was 307 and 361 days, and that of mares with
      mule foals 315 and 369 days, respectively. Additionally, we examined if the
      stallion, the mare, the age of the mare, the sex of the foal and the time of
      mating during the breeding season influenced gestation length of mares with mule
      foals and if the age of the mare, the sex of the foal and the time of breeding
      influenced gestation length of mares with "Freiberger" foals. The time of
      breeding and the mare had a significant (p < 0.05) influence on gestation length.

PMID- 9281061
TI  - [Veterinary services on the Internet].
AB  - The world wide web (www) on the internet is already a rich source of veterinary
      informations and offers several world wide discussion fora for problems of
      veterinary practice. With this article, we provide practical tips for first-time
      users of the www and encourage exploration of this new information technology for
      continuing education. The Swiss Drug Compendium is now accessible on www and-in
      the near future-the exchange and interpretation of laboratory results and
      diagnostic images via internet seems feasible.

PMID- 9281062
TI  - [Retropharyngeal abscess in cattle. A case report].
AB  - This case report describes history, clinical, laboratory, radiographic, and
      endoscopic findings, therapy, and outcome of a 5-year-old cow, suffering from
      retropharyngeal abscessation. Clinical findings at admission included elevated
      body temperature, head and neck held in extended position, excessive salivation,
      swelling of the retropharyngeal area, and slight inspiratory noise. Radiographic
      and endoscopic examination confirmed the tentative diagnosis of retropharyngeal
      abscessation. Treatment consisted of parenteral application of procaine
      penicillin for 10 days and local application of linseed rubefacients for 2 weeks.
      At that time, abscessation had developed. The abscess was subsequently
      surgically, approached by a modified Whitehouse approach. During this procedure,
      the abscess drained into the oropharynx, allowing interruption of surgery. Five
      months later, clinical, radiographic, and endoscopic follow-up examination
      revealed complete healing of the retropharyngeal abscess.

PMID- 9281063
TI  - [Urinary incontinence in castrated bitches. 2. Diagnosis and treatment].
AB  - Urinary incontinence due to spaying is caused by a sphincter incompetence of the
      urethra. In practice the diagnosis is established by ruling out other causes of
      incontinence such as neurological disease, bacterial cystitis, urinary tract
      malformation, iatrogenic ureterovaginal fistula and neoplasia of the urinary
      tract. An accurate diagnosis of urethral sphincter incompetence is made by
      urethral pressure profilometry. A urethral closure pressure of 7.4 cm H2O allowed
      the differentiation of bitches with urinary incontinence, due to spaying, from
      healthy control dogs with a diagnostic accuracy of 91%. For therapy alpha
      adrenergic drugs (Ephedrine or Phenylpropanolamine) are recommended, which result
      in continence in 74% and improvement in 24% of incontinent patients. In the
      absence of response estrogens may be used. If the medical therapy fails to
      achieve urinary continence, the endoscopic injection of collagen into the
      submucosa of the proximal urethra can be performed. This is a simple and
      minimally invasive procedure. It rarely leads to complications and may be
      repeated when necessary. The method is successful in 75% of cases.

PMID- 9281064
TI  - Corn genome initiative.

PMID- 9281065
TI  - Corn genome initiative.

PMID- 9281066
TI  - Telomerase activity of reverse transcriptase.

PMID- 9281067
TI  - Science and God: a warming trend?

PMID- 9281068
TI  - Panel calls falsification in German case 'unprecedented'.

PMID- 9281069
TI  - Worm longevity gene cloned.

PMID- 9281070
TI  - Schizophrenia clues from monkeys.

PMID- 9281071
TI  - Drug firms back move to link databases.

PMID- 9281072
TI  - The chameleon within: improving antigen delivery.

PMID- 9281073
TI  - Telomerase and retrotransposons: which came first?

PMID- 9281074
TI  - Expression cloning in the test tube.

PMID- 9281075
TI  - Laser-controlled cells.

PMID- 9281076
TI  - Selecting the needle.

PMID- 9281077
TI  - Success in breast-feeding.

PMID- 9281078
TI  - A novel way to identify a cobra bite.

PMID- 9281079
TI  - [Diagnostic difficulties in renal leiomyosarcoma. Case report and review of the
      literature].
AB  - The authors report a case of renal leiomyosarcoma and a review of the literature,
      underlining the difficulties of making a correct differential diagnosis with the
      benign neoplasms of the kidney and in performing correct surgical therapy.

PMID- 9281080
TI  - [Detection of the human papillomavirus in hyperplastic and cancerous prostatic
      tissue with PCR].
AB  - Human papillomavirus (HPV) infections are frequently associated with benign, pre
      malignant and malignant lesions of the female genital region and male anogenital
      tract. Recently several studies have been performed to evaluate the presence of
      HPV in the adenomatous and carcinomatous prostatic tissue for the epidemiological
      implications due to the sexual transmission, and for the possible etiologic role
      in the development of prostatic carcinoma, first cause of death from neoplasia in
      men over 60 years in the developed countries. The role of HPV is still
      controversial since some authors evidenced the virus in prostatic tissue others
      did not detect its presence. We investigate the presence of HPV in 60 prostatic
      benign hyperplasias and in 5 prostatic carcinomas in surgically resected
      prostates by PCR technique using consensus and type specific primers. The
      analyzed specimens were negative for HPV DNA, although appropriate amplimers were
      present for beta-globin and positive controls. We therefore conclude that HPV
      infections are not commonly found in the human prostate.

PMID- 9281081
TI  - [Etiologic, prognostic and social health aspects of urinary infections in
      hospitalized elderly with an indwelling urinary catheter].
AB  - The aim of the study is to evaluate, in a short case-report, the concomitant
      urinary tract infections in a group of institutionalized elderly people with
      urinary indwelling catheter. Mental, functional and sanitary status was
      determined. 61 subjects over 65 years old (23 male and 38 female) were recruited
      and subdivided into three groups. Streptococcus faecalis was the main cause of
      urinary tract infections, Gram negative infections were overall predominant. High
      levels of dysautonomia with strong, global cognitive ability compromise were
      present in 75% of pattern. DMI and RSS test showed a marked not self-contained in
      77% of recruited people and a high stress in the relatives. A significant
      statistical correlation among functional, sanitary, status and outcome
      institutionalization was present.

PMID- 9281082
TI  - [The role of transdermal anesthesia with EMLA in urologic surgery].
AB  - The review of 50 cases of urologic diseases has allowed us to show the utility of
      EMLA; even if it has been limited by some practical factors, it has permitted
      alone or as a first step in local and loco-regional anesthesia, to carry out
      surgical urologic procedures, with good surgical conditions, both for the surgeon
      and for the patient.

PMID- 9281083
TI  - [Follow-up of testicular tumors in the metastatic diffusion phase. Current
      orientation].
AB  - Lymphadenectomy in germinal tumors of the testis, in spite of the immediate
      morbility (postoperative complications) and of the permanent morbility
      (unejaculation), is still, as regards the group of non-seminoma neoplasms, the
      most suitable for survival. However, groups of oncologists are seeking the
      possibility of avoiding this technique at stage I and II of the lesions, with the
      help, of course, of careful observation by CT, NMR, markers. The use of combined
      therapies (chemotherapy and radius therapy) has increased survival and the
      patients' life, allowing a highly satisfying percentage of recovery also in the
      non-initial stages.

PMID- 9281084
TI  - [Perirenal immunoblastic lymphoma. Description of a case].
AB  - The primary perirenal localization of non-Hodgkin lymphomas is rare and normal
      methods of image diagnosis do not enable a reliable preoperative diagnosis. In
      the majority of cases renal function is not affected and this pathology is often
      presented as an occasional finding. The pathologies included in the differential
      diagnosis are renal neoplasias, abscess and inflammatory processes in a perirenal
      site. Echotomography shows the lesion as an hypoanechoic zone surrounding the
      kidney. Computed tomography show it as isodense with the renal parenchyma.
      Histological tests together with immunohistochemical tests identified a malignant
      large B cell immunoblastic-type lymphoma in the case described here, with
      plasmoblastic-plasmocytic differentiation and high malignancy according to the
      Working Formulation. The pathogenesis of this rare localisation is controversial.
      We maintain that lymphomatous proliferation may be triggered off by lymphatic
      follicles present in the perirenal space. The concomitant presence of other
      clinical signs, such as splenomegalia and adenopathies, may contribute to the
      diagnosis. On the contrary, monolateral involvement in the absence of other
      signs, as in this case, raises considerable problems of differential diagnosis.
      Perirenal lymphoma must therefore always be borne in mind in the diagnosis of
      renal or perirenal masses.

PMID- 9281085
TI  - [Veterinary dentistry (13). The use of the combination medetomidine/ketamine in
      dogs for anesthesia in dental procedures: evaluation of its clinical
      application].
AB  - The use of a combination of medetomidine and ketamine as anaesthetic for dental
      surgery was investigated in 60 dogs. The nature of the interventions varied from
      inspection of the teeth with cleaning of the teeth or simple tooth extraction to
      extraction of one or more dental elements or endodontic treatment. The operations
      lasted between 20 and 70 minutes, with an average of 34 +/- 15 minutes.
      Medetomidine, 1000 m g/m2 body surface administered intramuscularly, was used as
      premedication. Anaesthesia was induced with intravenously administered ketamine
      at a dose of 2-3 mg/kg body weight. The effect of premedication was 'good' in
      79.5% of patients, 'moderate' in 12%, and 'poor' in 8.5%. Seven patients were
      given additional 50% medetomidine, which caused the proportion of animals with
      'good' premedication to increase to 91.5%. Twelve of the 60 patients showed
      convulsion-like symptoms of varying severity directly after the administration of
      ketamine. In 4 patients the tonic cramps were considered severe enough to warrant
      once-only administration of midazolam. The quality of anaesthesia in the
      maintenance phase was considered 'good' in 88% of the patients and 'moderate' in
      12%. Recovery was 'good' in 74% of the patients, 'moderate' in 11%, and 'poor' in
      15%. Heart rate after premedication with medetomidine was 53 +/- 3 beats per
      minute and increased to 86 +/- 4 beats per minute (P < 0.05) after administration
      of ketamine. It thereafter decreased, over a period of 20 minutes, to 60 +/- 3
      beats per minute. The respiration rate was 15 +/- 1 per minute and remained
      unchanged throughout the operation. After completion of surgery, medetomidine was
      antagonized with atipamezole (2500 m g/m2) given intramuscularly. In 13% of the
      animals the recovery period was characterized by tremors and restlessness. It can
      be concluded that the combination medetomidine and ketamine provides adequate
      analgesia, hypnosis, and muscle relaxation for various dental surgical
      interventions to be performed.

PMID- 9281086
TI  - [Pioneers: veterinarians from earlier times (21). Johann Jacob Rychner (1803
      1878)].

PMID- 9281087
TI  - [Bovine spongiform encephalopathy (BSE): clinical aspects, duty of notification
      and consequences of positive findings].

PMID- 9281088
TI  - [Pig farmer and veterinarian: a pair apart].

PMID- 9281089
TI  - [Medicated fodder with or without A, D and K additives].

PMID- 9281090
TI  - [Inspections of veterinary practices by the Veterinary Inspection and the General
      Inspection Service].

PMID- 9281091
TI  - [Proceedings of the 3rd session of the (all-Russian) Dental Association. Moscow,
      9-13 September 1996].

PMID- 9281093
TI  - [The development of science under current economic conditions].

PMID- 9281094
TI  - [The development of principles for performing the certification of dentists and
      the expert assessment of dental institutions and enterprises in licensing and
      accreditation].

PMID- 9281092
TI  - [The stomatological morbidity of the population of Russia and the planning
      principles for prevention programs].

PMID- 9281095
TI  - [Professional standards].

PMID- 9281096
TI  - [The unresolved problems in the certification of medical dental personnel].

PMID- 9281097
TI  - [Pressing tasks in the computerization of the dental service of Russia].

PMID- 9281098
TI  - [The organization of the work of the dental institutions in Samara Province under
      the conditions of the new mechanism in public health and the system of obligatory
      medical insurance].

PMID- 9281099
TI  - [The organization of primary prevention in the prophylaxis of lesions of the hard
      dental tissues in persons having occupational contact with cadmium salts].

PMID- 9281100
TI  - [The organization of the primary prevention of dental caries among young children
      under the new socioeconomic conditions].

PMID- 9281101
TI  - [Problems of price formation in the organization of specialized orthodontic care
      for adult patients under cost accounting].

PMID- 9281102
TI  - [An analysis of the organization of consultative care for the adult population of
      the Soviet District in the city of Omsk].

PMID- 9281103
TI  - [Organizational problems in the instruction and advanced training of
      orthodontists].

PMID- 9281104
TI  - [The results of the medical economics quality control of dental care in the
      system of obligatory medical insurance based on data from the treatment
      institutions of Rostov Province].

PMID- 9281105
TI  - [The combined treatment of periodontal diseases at a periodontics office].

PMID- 9281106
TI  - [A comprehensive informational-instructional program for the prevention of
      stomatological diseases in school: The Day of Stomatological Disease Prevention].

PMID- 9281107
TI  - [The organization of dental care for patients with concomitant somatic diseases
      at a day hospital in the city of Saint-Petersburg].

PMID- 9281108
TI  - [A model outline of the organizational and medical measures for the introduction
      of milk fluoridation projects in different regions of Russia].

PMID- 9281110
TI  - [The socioeconomic efficiency of using low-intensity laser radiation in pediatric
      dental practice].

PMID- 9281109
TI  - [Validation of the need for performing the prophylaxis of mouth diseases among
      the workers of a chemical plant putting out complex liquid fertilizers].

PMID- 9281111
TI  - [Dental care for children during the transition to market relationships].

PMID- 9281112
TI  - [The economic basis for the work of the dental service in an agricultural
      region].

PMID- 9281114
TI  - [The organization of a quality control system in dental care].

PMID- 9281113
TI  - [The materials and equipment basis of an orthodontic clinic].

PMID- 9281116
TI  - [The economic and organizational bases of the treatment of patients by law making
      use of free dental prosthesis].

PMID- 9281117
TI  - [The organizational problems of individualized prophylaxis in a dental
      polyclinic].

PMID- 9281115
TI  - [The needs of the population of Omsk Province for different designs of dentures].

PMID- 9281118
TI  - [The organization of orthodontics instruction for students and the postgraduate
      training of specialists in this field].

PMID- 9281119
TI  - [The functions of professional standards].

PMID- 9281121
TI  - [The principle of cost accounting for the conventional unit of man-hours per job
      in delivering paid services in dentistry].

PMID- 9281120
TI  - [The social and professional orientation of dental graduates in the Urals and
      Siberia].

PMID- 9281123
TI  - [The treatment of periodontitis--the status of the problem and the outlook for
      improvement].

PMID- 9281122
TI  - [The status and outlook for the prevention and treatment of suppurative
      inflammatory diseases of the maxillofacial area].

PMID- 9281124
TI  - [The diagnosis and treatment of complications in acute odontogenic infection].

PMID- 9281125
TI  - [Dental care for the pediatric population in the city of Moscow with inflammatory
      diseases].

PMID- 9281126
TI  - [The use of lasers and a plasma surgical unit in the combined treatment of
      patients with inflammatory diseases of the maxillofacial area].

PMID- 9281127
TI  - [Drug stimulation of the healing of suppurative wounds of the maxillofacial
      area].

PMID- 9281128
TI  - [The experimental evaluation of the efficacy of using a Rhodiola rosea extract
      for treating odontogenic inflammatory diseases].

PMID- 9281129
TI  - [The differentiated surgical treatment of odontogenic maxillary sinusitis].

PMID- 9281130
TI  - [The organization of specialized care for patients with diseases and traumatic
      lesions of the salivary glands].

PMID- 9281131
TI  - [The treatment of foci of chronic odontogenic infection by using the pulsed
      periodic CO2 laser scalpel].

PMID- 9281132
TI  - [Means for preventing odontogenic inflammatory diseases in servicemen of the
      Armed Forces].

PMID- 9281134
TI  - [The treatment of patients with odontogenic maxillary sinusitis at a dental
      polyclinic].

PMID- 9281135
TI  - [The procedure for removing the lower third molar and the prevention of
      inflammatory complications].

PMID- 9281133
TI  - [The basic treatment aspects of suppurative-inflammatory diseases via the
      regulated activity of wound enzymes].

PMID- 9281137
TI  - [The role of body reactivity in choosing the treatment strategy and procedure in
      acute inflammatory processes in the maxillofacial area].

PMID- 9281136
TI  - [Cardiolipin antibodies in patients with chronic parenchymatous parotitis,
      Sjogren's syndrome and disease and tumors of the parotid salivary glands].

PMID- 9281138
TI  - [The urease activity of the saliva in patients with acute odontogenic infection
      of the maxillofacial area].

PMID- 9281139
TI  - [Methods of efferent therapy in the combined treatment of contact odontogenic
      mediastinitis].

PMID- 9281140
TI  - [The enhancement of osseointegration with hydroxyapol in the surgical treatment
      of chronic periodontitis and periapical cysts].

PMID- 9281141
TI  - [The use of a radiosurgical method in the surgical treatment of inflammatory
      periodontal diseases].

PMID- 9281142
TI  - [The development and creation of a new generation of superoxide dismutase-based
      antioxidant preparations].

PMID- 9281143
TI  - [The use of dental elixirs based on natural biologically active substances in the
      treatment and prevention of periodontal diseases].

PMID- 9281145
TI  - [The use of extraoral compression-distraction osteosynthesis in treating patients
      with mandibular fractures with posttraumatic defects and complicated by a
      suppurative process].

PMID- 9281144
TI  - [The evaluation of the root canal microflora in periapical periodontitis in Saint
      Petersburg residents in different years].

PMID- 9281146
TI  - [Hemodynamic disorders and their correction in the treatment of patients with
      suppurative septic diseases of the face and neck].

PMID- 9281148
TI  - [The use of pulsed complexly modulated electromagnetic fields in treating the
      inflammatory mucosal manifestations of the denture bed].

PMID- 9281147
TI  - [The treatment of inflammatory suppurative-destructive processes of the
      maxillofacial area and neck by laser exposure of the carotid sinus].

PMID- 9281149
TI  - [The functional status of the kidneys in patients with phlegmons of the face and
      neck].

PMID- 9281150
TI  - [The characteristics of managing and treating patients with suppurative
      inflammatory processes of the maxillofacial area and diabetes mellitus].

PMID- 9281151
TI  - [The use of physiotherapeutic factors in the combined treatment of patients with
      diseases of the maxillofacial area].

PMID- 9281152
TI  - [The clinico-immunological diagnosis, prognosis and treatment follow-up in
      odontogenic abscesses, phlegmons and lymphadenitis].

PMID- 9281153
TI  - [The efficacy of using ozone in the combined treatment of disseminated
      odontogenic phlegmons of the maxillofacial area].

PMID- 9281155
TI  - [Postoperative complications in dental implantation].

PMID- 9281154
TI  - [The structural and etiological characteristics of inflammatory diseases of the
      maxillofacial area].

PMID- 9281156
TI  - [The role of the microflora infecting the dentin in caries and its complications
      in the development and spread of acute odontogenic and cross infectious
      diseases].

PMID- 9281157
TI  - [The apitherapy of apical periodontitis].

PMID- 9281158
TI  - [The use of ozonized solutions in the combined treatment of odontogenic
      putrefactive-necrotic phlegmons of the maxillofacial area and neck].

PMID- 9281159
TI  - [The importance of the immunogram for the prognosis of the course of odontogenic
      inflammatory diseases and of the performance of immunotherapy].

PMID- 9281160
TI  - [The evaluation of the status of the body's protective mechanisms in the clinical
      picture of odontogenic inflammatory diseases].

PMID- 9281162
TI  - [The pathogenetic treatment of chronic apical periodontitis].

PMID- 9281161
TI  - [The clinico-genetic diagnosis and prognosis of the inflammatory complications of
      mandibular fractures].

PMID- 9281163
TI  - [An experimental study of the use of Yag: Nd and YAG: Cr, Tm, Ho lasers in
      endodontics].

PMID- 9281164
TI  - [The therapeutic efficacy of probiotics for the correction of microfloral
      imbalance in periodontitis].

PMID- 9281165
TI  - [High-information symptoms in the diagnosis of phlegmon of the floor of the
      mouth].

PMID- 9281166
TI  - [Physical factors in the combined treatment of acute suppurative-inflammatory
      processes of the maxillofacial area].

PMID- 9281167
TI  - [The dental service under the new management conditions in light of the
      realization of the program of the Stomatology Association (All-Russian), A
      Strategy for the Development of Stomatology in Russia].

PMID- 9281168
TI  - [Mediastinitis--a severe complication of acute odontogenic inflammatory processes
      of the maxillofacial area].

PMID- 9281169
TI  - [A comparative evaluation of the autoimmune processes in inflammatory periodontal
      diseases].

PMID- 9281170
TI  - [The corrective treatment of patients with complicated mandibular fractures and
      defects using the kinesiology method of Gordon Stokes and Daniel Whiteside].

PMID- 9281171
TI  - [The x-ray diagnosis of sinusitis in patients with posttraumatic deformities of
      the middle and upper third of the visceral cranium].

PMID- 9281172
TI  - [The local immunity characteristics of the mouth in athletes during a period of
      intensive training].

PMID- 9281173
TI  - [The diagnosis of disseminated phlegmons and their complications and a strategy
      for their combined treatment].

PMID- 9281174
TI  - [The use of an electromagnetic field in the diagnosis of diseases of the apical
      periodontium].

PMID- 9281175
TI  - [The development of a complex of medical rehabilitative measures in acute
      pulpitis of the deciduous teeth].

PMID- 9281176
TI  - [One-step replacement of the fragmentary mandibular defects during the removal of
      suppurating benign formations].

PMID- 9281177
TI  - [Odontogenic inflammatory processes in children based on data from the Pediatric
      Dentistry Clinic of the Perm State Medical Academy].

PMID- 9281178
TI  - [The role of locally acting factors in the development of gingivitis in young
      people].

PMID- 9281179
TI  - [The local treatment of suppurative wounds of the maxillofacial area].

PMID- 9281181
TI  - [Bone brephoplasty in the treatment of periodontitis patients].

PMID- 9281182
TI  - [The prevention of odontogenic inflammatory diseases in children by improving the
      diagnosis and treatment of deep caries].

PMID- 9281180
TI  - [The role of opportunistic microflora in the development of postoperative
      suppurative-inflammatory complications in patients with cancer of the oral
      mucosa].

PMID- 9281183
TI  - [The development of a complex of preventive measures against hospital infections
      in surgical-type dental institutions].

PMID- 9281184
TI  - [A comparative evaluation of the efficacy of endolymphatically administered
      antibiotics in the combined treatment of phlegmons of the maxillofacial area].

PMID- 9281185
TI  - [Our experience with the treatment and prevention of acute suppurative
      complications in different surgical interventions in the oral cavity].

PMID- 9281186
TI  - [The problem of the antibacterial therapy of inflammatory diseases of the
      maxillofacial area].

PMID- 9281187
TI  - [Active detoxication methods in the combined treatment of torpid and chronic
      suppurative-inflammatory diseases of the maxillofacial area].

PMID- 9281188
TI  - [The atypical and chronic course of suppurative inflammatory diseases of the
      maxillofacial area and the diagnostic and treatment methods].

PMID- 9281189
TI  - [Homeostatic disorders and their correction in a program of combined treatment in
      odontogenic sepsis].

PMID- 9281190
TI  - [The combined treatment of suppurative wounds of the maxillofacial area and neck
      in children].

PMID- 9281191
TI  - [The immunomodulating therapy of odontogenic phlegmons with complexes of
      antibacterial preparations and water-soluble polymers for medical use].

PMID- 9281192
TI  - [Chronic stomatologic endotoxicosis].

PMID- 9281193
TI  - [A comprehensive method for the early detection and differential diagnosis of the
      intracranial complications of suppurative diseases of the face and neck].

PMID- 9281194
TI  - [Osteoplasty and ozone therapy in the treatment of a severe degree of generalized
      periodontitis].

PMID- 9281195
TI  - [The prevention of suppurative processes in gunshot fractures of the mandible].

PMID- 9281196
TI  - [The simultaneous sanative treatment of foci of odontogenic and cardiogenic
      infections during the surgical treatment of septic endocarditis].

PMID- 9281197
TI  - [Generalized periodontitis in the Ehlers-Danlos syndrome type VIII (a familial
      case)].

PMID- 9281198
TI  - [The organizational problems of preventing cross infection in orthodontic
      departments and offices].

PMID- 9281200
TI  - [The genetic effects in the somatic cells of persons working under chronic
      irradiation of different intensities after the accident at the Chernobyl Atomic
      Electric Power Station].
AB  - A complex genetic study of two groups from of Chernobyl NPP personnel (from
      "Shelter" unit and 3rd Block) has been carried out using classical cytogenetic
      and GPA methods. The first group was the most vulnerable from the viewpoint of
      accumulated dose (exceeding 25 cGy for the moment of study). Positive correlation
      between individual and group frequencies of cytogenetic markers of irradiation
      (stable and unstable chromosomes aberrations) and NO mutations in the GPA locus
      was found.

PMID- 9281201
TI  - [Free radicals in the origin and clinical manifestation of Down's syndrome].
AB  - The high level of free radicals and antioxidant protection disbalancing cause the
      chromosome nondisjunction in meiosis, appearance of trisomy 21 and fetuses with
      Down's syndrome, age-dependent pathology, of parent's mosaic clone, clinical
      manifestations of the syndrome, diseases in relatives, recurrent cases of trisomy
      21. The comparative analysis of clinical traits of Down's syndrome and
      pathological changes in families with after-effects of radiation exposure was
      carried out. The factors causing an increase in the level of free radicals were
      considered.

PMID- 9281199
TI  - [A comparative study of the effects of laser and light-emitting diode radiations
      in the red spectrum on the clinical course of periodontal diseases and on
      microcirculatory processes in an experiment].

PMID- 9281203
TI  - [Genetic differences in breeds in milk quality indices].

PMID- 9281202
TI  - [A diagnostic analysis of a genetic mutation associated with a deficiency of
      leukocyte adhesion in cattle].
AB  - Bovine leukocyte adhesion (BLAD) is a recessive autosomal disease in Holstein
      Friesian cattle caused by point mutation in CD18 gene encoding neutrophil-surface
      glycoprotein. To determine BLAD carriers, the convenient primers were chosen to
      amplify the mutant region of gene with the following restriction analysis. A
      screening program for BLAD has been initiated. Among 190 animals from different
      Ukrainian farms 6 were heterozygous according to the tested trait, i.e., BLAD
      deficient. No homozygous BLAD carriers were detected.

PMID- 9281204
TI  - [Chromosomal polymorphism: the biological and medical aspects].
AB  - The review on the problem of human chromosomal polymorphism is presented.
      Biological nature of polymorphism of heterochromatin as well as its different
      phenotypes were considered. Prospects of chromosomal polymorphism study in the
      future for investigation of different forms of pathology were also discussed.

PMID- 9281206
TI  - [Medical genetics in Ukraine: reflections after a congress].

PMID- 9281205
TI  - [The genetic bases of the lipid metabolic disorders in atherosclerosis].
AB  - The development of dyslipoproteinemia is to a large extent genetically
      determined. The mutations in gene controlling receptor to lipoproteids of low
      density, the genes Apo B, Apo A-1, and Apo E have a dominant role in the
      disturbance of lipid metabolism. The development of atherosclerosis at young age
      is apparently associated with the mutations in gene of receptors, in the gene Apo
      B and some mutations in a cluster of the genes A-I--CIII--AIV.

PMID- 9281207
TI  - [Adverse effect of tobacco smoking on wound healing].

PMID- 9281208
TI  - [Adverse effects of drugs--25 years later].

PMID- 9281209
TI  - [Tension headache].

PMID- 9281210
TI  - [Challenges and therapeutic results of ear surgery].

PMID- 9281211
TI  - [Effects of tobacco smoking on the incidence of flap necrosis after mastectomy].
AB  - One hundred and fifty-nine women undergoing mastectomy (simple or modified
      radical) were followed for the development of flap necrosis. The incidence of
      flap necrosis was found to 14%. The only significant risk factor for the
      development of flap necrosis was found to be smoking, which increased the risk by
      4.9 times. The effects of nicotine and carbon monoxide, the two principal known
      detrimental factors in tobacco smoke, are described. Prophylactic efforts are
      advised.

PMID- 9281213
TI  - [Bone loss and oral health status in patients on home parenteral nutrition].
AB  - The mandible and forearm bone mineral content and dental and periodental state
      were studied in 15 patients, aged 26 to 65 years, on home parenteral nutrition
      due to short bowel syndrome and compared to the findings in a normal population.
      The bone mineral content was measured by dual-photon absorptiometry. All patients
      were on free oral intake as a supplement to the parenteral nutrition. Forty-seven
      percent of the patients showed mandibular osteoporosis. Thirty-three percent had
      osteoporosis in the forearm and also radiographic signs of osteoporotic fractures
      of the columna. The dental and periodental state did not differ from that of the
      normal Danish population of the same age. Thus, patients on home parenteral
      nutrition due to short bowel syndrome seem to have a high risk of developing
      systemic osteoporosis, including the jaws, but apparently do not have a higher
      risk for deterioration of the dental or periodental state.

PMID- 9281214
TI  - [Diabolic hiccup].
AB  - Hiccup is a brief involuntary inspiratory movement followed by glottal closure.
      Transitory hiccup is usually caused by epigastric irritation. Rarely, hiccup may
      last for a long time, and is known as diabolic hiccup. A case is described of
      diabolic hiccup due to a unilateral lesion of nucleus tractus solitarius in the
      brainstem. This probably resulted in release of inhibition of the hiccup reflex.
      Therapeutic suggestions in diabolic hiccup are chlorpromazine, baclofen,
      valproate and nifedipine.

PMID- 9281212
TI  - [Randomized population study of screening for intestinal cancer with Hemoccult
      II].
AB  - The aim of the randomised study was to compare mortality rates from colorectal
      cancer (CRC) in persons screened with faecal occult-blood tests every two years
      during a 10-year period with those of unscreened similar controls. Thirty
      thousand nine hundred and sixty-seven persons aged 45-75 years in 1985 were
      allocated to screening and another 30,966 to a control group. Only participants
      who completed the first round with Hemoccult-II were invited for further
      screening. Participants with positive tests were offered colonoscopy. The primary
      endpoint was death from CRC. Sixty-seven percent completed the first screening
      round, and of these more than 90% accepted repeated screenings. During the 10
      year study, 481 persons in the screening group had a diagnosis of CRC, compared
      with 483 unscreened controls. CRC mortality was significantly lower in the
      screening group (205 deaths) than in controls (249 deaths) (mortality ratio 0.82
      [95% conf. lim. 0.68-0.99], p = 0.03). Our findings indicate that biennial
      screening by faecal occult-blood tests can reduce CRC mortality.

PMID- 9281215
TI  - [Pancreatic fracture diagnosed by ultrasound].
AB  - A case of complete fracture of the pancreas diagnosed preoperatively by
      ultrasound is reported. The diagnosis was confirmed intraoperatively and a Roux
      en-Y-pancreaticojejunostomy was performed. A prominent role of ultrasound in the
      acute evaluation of the abdomen following blunt trauma is recommended.

PMID- 9281216
TI  - [Screening for colorectal cancer with fecal occult blood--an offer to the
      population?].

PMID- 9281217
TI  - [Sunscreens should not be used to prolong exposure to sun].

PMID- 9281218
TI  - [Volume of synovial membrane and synovial fluid determined by MR-imaging].

PMID- 9281219
TI  - [Connection between reading disability/dyslexia and hyperactivity].

PMID- 9281220
TI  - [Electrophoretic characteristics of integrin++ beta1 subunit from human smooth
      muscles].
AB  - Total fraction of beta 1 integrin family was isolated from human smooth muscle by
      affinity chromatography on immobilized anti-beta 1 monoclonal antibodies. SDS
      PAGE analysis and subsequent immunoblotting demonstrated that integrin samples
      contain unknown before high molecular mass (205 kD-nonreduced and 230 kD-reduced)
      material immunologically related to beta 1 integrin subunit. One dimensional
      peptide mapping showed that the 205 kD protein is not a novel beta 1 related
      integrin subunit, but a beta 1 integrin subunit dimer. Reduction of
      electrophoretic samples with dithiothreitol led to the removal of the major part
      of the beta 1 immunoreactive material from 205 kD to 130 kD region, indicating a
      disulfide nature of B1 integrin subunit dimer. The 230 kD protein turned out to
      be an only partly reduced beta 1 integrin disulfide bonded dimer. Possible in
      vivo existence of the disulfide bonded dimer and oligomer integrin forms is
      discussed.

PMID- 9281221
TI  - [Miniature thin layer biosensors which are sensitive to glutamate and glutamine].
AB  - Integrated thin film biosensors for simultaneous measurement of L-glutamine and L
      glutamate in a micro-flow cell were developed. Due to a novel glutaminase with an
      activity optimum in the neutral pH range a direct monitoring of glutamine in
      mammalian cell culture medium could be performed. The glutamine bienzyme sensor
      was prepared by coimmobilization of glutaminase with glutamate oxidase within a
      photo patterned poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogel membrane. The
      sensor response is linear in the concentration range of 55 mmol to 10 mmol
      glutamine/l. Additionally a glutamate biosensor is integrated on the sensor chip
      for difference measurement of possible glutamate interferences. The sensor chip
      can be used for at least 300 measurements without any alteration in the
      performance of its sensors. A new sensor chip with an integrated flow cell
      provides the possibility of simultaneous measurement of four different parameters
      at a cell volumina of 1 ml. Completing the microsystem a battery operated surface
      mounted device (SMD) potentiostat was developed to get a "lab on chip".

PMID- 9281222
TI  - [Relation between the energy state and permeability of cardiomyocyte sarcolemma
      during "calcium paradox" and activity of glycolysis].
AB  - Reperfusion by Ca(2+)-containing solution after 10 minutes of Ca(2+)-depletion
      resulted in the loss of myoglobin, depletion of ATP and phosphocreatine (calcium
      paradox). Exhaustion of high energy phosphates exacerbated when glucose was
      substituted by pyruvate or acetate. Iodoacetate (30 mcM) elevated loss of
      myoglobin due to calcium paradox. Addition of 120 mM glucose reduced loss of
      myoglobin and depletion of high energy phosphates after induction of the calcium
      paradox. There is a close correlation between concentration of lactate and ATP in
      the hearts subjected to calcium paradox. Elevated activity of glycolysis
      protected hearts against the calcium paradox.

PMID- 9281223
TI  - [Nonviral methods of gene transfer in gene therapy].
AB  - A number of viral and non-viral vector systems have been developed nowadays for
      gene therapy applications. The advantages and shortcomings of the following non
      viral methods of transfection are discussed in this review: calcium phosphate
      technique, ballistic transfection using "gene gun", electroporation,
      microinjection into the nucleus, receptor-mediated gene transfer, and artificial
      macromolecular complexes (polycations, hydrophobic polycations, polymers,
      cationic and neutral liposomes). Special attention is paid to methods of
      lipofection based on the usage of cationic and neutral liposomes as well as
      targeted gene delivery with the emphasis on the works which were out in author's
      laboratories.

PMID- 9281224
TI  - [Immunochemical correlates of the severity of Parkinson's disease].
AB  - The serum samples from 29 patients with Parkinson's disease were analysed for the
      levels of the autoantibodies (a-AB) and antiidiotype antibodies (AIAB) to the
      proteins of nervous system S-100, GFAP, NKP and MP-65. High levels of a-AB or
      AIAB to at least 3 proteins were seen in patients with severe course of the
      disease. No significant changes of these levels were observed in patients with
      light course of the disease. The plasmapheresis was carried out to some patients
      with severe course of the disease. After this procedure the decrease of
      neurological deficit from number 21 +/- 2 to 8 +/- 1 on Webster's scale and
      decrease of a-AB and AIAB levels to normal values (in some cases it became lower
      than normal values) were observed. It can be concluded that the levels of the a
      AB to the nervous tissue proteins correlate with clinical condition of the
      patient.

PMID- 9281225
TI  - [The search for new antiulcer agents using a computer system for predicting the
      antiulcer activity].
AB  - Specialised system for computer assisted prediction of antiulcer activity of
      chemical compounds on the basis of their structural formulae is described.
      Predicted activity spectrum includes antiulcer activity, antisecretory and
      gastroprotective effects; H2- and M1-receptors blockade, H+, K(+)-ATPase
      inhibition as the mechanisms of antisecretory effect. It is shown that the
      average prediction accuracy is 83% in leave-one-out cross validation and 82% for
      the independent test set. Prediction made for about 300 new chemical compounds
      provides the selection of 20 potential antiulcer agents, 9 of them were
      synthesised and tested, 5 compounds have potent antiulcer activity. The
      discovered antiulcer agents are classified as New Chemical Entry because
      antiulcer and close effects have not been earlier for any compound of this
      chemical series.

PMID- 9281226
TI  - [Sleep disorders: disease entities, symptoms or playing field of specialists?].

PMID- 9281227
TI  - [Amylin/IAPP (islet amyloid polypeptide)--physiology and clinical significance].
AB  - Amylin or islet amyloid polypeptide (IAPP) is the protein component of amyloid
      deposits commonly seen in pancreatic islets of patients with type 2 diabetes
      mellitus. In in vitro and in animal studies amylin has been shown to decrease
      insulin secretion and induce insulin resistance. Amylin is stored in the beta
      cells and released together with insulin. Circulating amylin is increased in
      obesity, hypertension and pregnancy, while it is absent in type 1 diabetes
      mellitus. In type 2 diabetes mellitus the secretion of amylin is impaired prior
      to that of insulin. Infusion of amylin in man in doses leading to pharmacological
      levels did not cause any decrease of insulin sensitivity but an impairment of
      insulin secretion occurred. The recent availability of an amylin antagonist
      confirmed the effect of amylin on the decrease of insulin secretion in man. The
      kinetic pattern of amylin, which is presumably excreted by the kidneys, closely
      resembles that of C-peptide. Subcutaneous administration of the amylin agonist,
      pramlintide, delays gastric emptying in patients with type 1 diabetes mellitus
      and, thus, reduces postprandial hyperglycemia. In summary, there is evidence that
      amylin is able to regulate insulin secretion and gastric emptying in man, but
      further proof is required.

PMID- 9281228
TI  - [Gene transfer into the patellar tendon of rabbits: a preliminary study of
      locoregional expression of growth factors].
AB  - Growth factors have the potential to enhance native repair responses in
      ligamentous and meniscal lesions. However, methods for applying these cytokines
      to sites of injury for extended periods are lacking. We suggest that local
      transfer of genes which encode the relevant healing factors merits investigation
      as a potential solution to this problem. In the present study different viral
      vectors and liposomes were evaluated for their ability to deliver genes to cells
      of ligamentous and meniscal origin. The anterior (ACL) and posterior (PCL)
      cruciate ligaments and the medial collateral ligament (MCL), semitendinosus
      tendon, patellar tendon, and menisci were removed from New Zealand white rabbits
      Cells grown from these tissues were then investigated for their susceptibility to
      genetic alteration by these vectors. Based upon the ability of these vectors to
      convert cells in culture to a lacZ(+) phenotype, adenovirus was the most
      effective vector in short-term experiments. However, expression was transient.
      Although retrovirus gave lower initial transduction efficiencies, the percentage
      of transduced cells was increased by the use of the selectable marker gene
      neo(r). Cells infected with adeno-associated virus containing the neo(r)-gene
      were also selected in this way. Liposomes showed low efficiency of gene transfer
      and expression. In an in vivo marker study we injected adenovirus into the rabbit
      patellar tendon. Transduced cells were observed mainly in the subsynovial layer
      at a declining frequency over a 6-week period. The allogeneic transplantation of
      retrovirally-transduced fibroblasts into the patellar tendon resulted in a
      greater number of transduced cells. Although the number of lacZ(+) cells declined
      with time, positive cells were still present 6 weeks after transplantation.
      Furthermore, the transplanted cells, unlike cells transduced in situ with
      adenovirus, migrated from the injection site and integrated into the crimp of the
      tendon.

PMID- 9281229
TI  - [Clinical aspects of sleep disorders--experiences with 817 patients of an
      ambulatory sleep clinic; comment].
AB  - Between 1992, the year in which the Sleep Out-Patient Clinic at the Department of
      Psychiatry, University of Vienna, Allgemeines Krankenhaus (General Hospital)
      Vienna, was established, and 1996, 817 patients (58% females, average age 52
      years; 42% males, average age 48 years) were treated for sleep disorder.
      According to the International Statistical Classification of Diseases and Related
      Health Problems (ICD-10) of the World Health Organization (WHO), 70% of the
      patients presented with a non-organic sleep disorder and 30% with an organic
      sleep disorder as main diagnosis. Non-organic insomnia was by far the most
      frequently diagnosed sleep disorder (48%), while within the organic sleep
      disorders sleep apnea was dominant (12%). In regard to the additional non-organic
      (mental disorder) diagnoses rounding off the clinical picture, neurotic, stress
      related, and somatoform disorders were the most common (41%), followed by
      affective disorders (31%) and mental and behavioural disorders due to intake of
      psychoactive substances, e.g. alcohol, drugs (15%). Additional organic diagnoses
      related to sleep disorders involved primarily endocrine disorders such as
      adipositas (23%), followed by cardiovascular disorders (19%), and primary snoring
      (17%). The sleep out-patient clinic has at its disposal a supportive diagnostic
      armamentarium such as all-night sleep polysomnography, 24-hour polysomnography,
      the Multiple Sleep Latency Test, EEG and EEG-mapping in the affiliated sleep
      laboratory, the evaluation of event-related potentials (P300) and actometry in
      the psychophysiological laboratory, as well as psychological and
      psychophysiological tests in the clinical psychodiagnostic laboratory, in order
      to determine the right treatment or preventive measures for the individual
      patients.

PMID- 9281230
TI  - [Cardiopulmonary resuscitation already in Egypt 5,000 years ago?].
AB  - In light of the medically relevant features of the ancient Egyptian mouth-opening
      ceremony, the question of the effectiveness of medical practices in Egypt
      thousands of years ago is examined, whereby the religious and cultural framework
      also plays a significant role. In the Land on the Nile myth and reality clearly
      generated special conditions which favoured the systematic treatment of questions
      of resuscitation. Numerous examples show that this had practical consequences in
      the area of everyday medicine. In addition, rebirth and resurrection were central
      elements of the cult of the dead which had exact medical equivalents. These
      equivalents may demonstrate the advanced state of resuscitation practices in
      Egypt at that time. In this context, a reconstruction of an ancient Egyptian
      mouth-opening instrument is presented. In the cult of the dead, this instrument
      played a role which can be compared to the function of a modern laryngoscope. It
      appears possible that at the time of the pyramids the Egyptians already had an
      understanding of the technology required to perform instrument-aided artificial
      respiration. Whether or not they actually possessed a fundamental knowledge of
      the principles of cardio-pulmonary resuscitation remains unclear. Nevertheless,
      the astonishingly functional characteristics of the reconstructed mouth-opening
      instrument suggest that it was developed for more than purely symbolic purposes.

PMID- 9281231
TI  - [Insulin therapy: an ongoing topic].

PMID- 9281232
TI  - [Insulin therapy: basic principles and strategy].
AB  - Proper insulin therapy requires close interaction between the patient and his
      doctor. The still used strategy of conventional insulin treatment employing 1 to
      2 insulin injections per day does not suffice to avoid diabetes associated
      complications. Intensified forms of insulin treatment, however, permit in part
      "near-normalization" of blood glucose and delay the development of late diabetic
      complications. Intensified insulin replacement derives its strategy from
      knowledge about physiological insulin release and requires the patient, and this
      applies in particular to "Functional Insulin Therapy (FIT)", to measure his blood
      glucose frequently and to correct aberrant blood glucose values by additional
      insulin or glucose as necessary. To reach the goal of good metabolic control
      needs medical guidance of the appropriately trained patient, who, as well as the
      attending team, requires continuous remotivation to co-operate.

PMID- 9281233
TI  - [Insulin therapy of type I diabetes].
AB  - Type 1 diabetes is a disease due to hormone deficiency. Therefore treatment with
      insulin is hormonal substitution and should be done according to physiological
      data with 4 injections NPH-insulin and 3 preparandial injections of regular
      insulin before the main meals. Intensified insulin treatment should be separate
      substitution of basal and prandial insulin need. The basal insulin substitution
      should be tested by a fasting day over 24 h giving only basal insulin. Insulin
      treatment has to be supplemented by diabetes education, blood glucose self
      control and regulation of diet and exercise. Target values are blood glucose
      concentrations of 80 to 120 mg/dl fasting and before the main meals, 110 to 160
      mg/dl at bedtime and above 65 mg/dl after midnight. A written plan with the
      algorithms of insulin substitution is helpful for the care of the diabetic
      patient. A successful insulin treatment is assessed by a HbA1c of 7.x without
      hypoglycemias.

PMID- 9281234
TI  - [Insulin therapy in type II diabetes].
AB  - The results of conventional intensified insulin therapy (4 injections per day) in
      type II diabetics correspond more to those of conventional therapy (2 injections
      per day). Compared to a conventionally treated collective with strict dietetic
      regimen the intensified treated type II diabetics did not lead to an improved
      metabolic control. The frequency of hypoglycemic episodes did not differ in both
      collectives. Intensified insulin therapy is associated with subjectively
      increased comfort and increased life quality despite the seldom use of the
      advantages of the therapy. The management of the intensified therapy probably has
      to be learned in an earlier stage of life and requires repeated and more
      intensified education in elderly patients. The regression of typical late
      complications of diabetes mellitus as seen in the DCCT may possibly be achieved
      by a greater effort in therapy and empowerment of the patient.

PMID- 9281236
TI  - [Insulin therapy and sports].
AB  - Physical work effects a transitory enhanced affinity of insulin to its receptor
      in the stressed muscles and thereby a better efficiency. Therefore, in sports
      lasting for 30 min and more the basal and/or bolus doses of insulin have to be
      reduced in order to prevent hypoglycemia. An alternative supply of additional
      carbohydrates prior to physical work is often not practicable. Injections of
      insulin into areas of the body not involved in muscular work do not give
      sufficient warranty against hypoglycemic reactions. A new short-acting insulin
      analogue (Lispro) shows a reduced effect on blood glucose levels after 3 h as
      compared to regular insulin. Therefore, it could be of advantage for insulin
      dependent diabetics doing their exercise at this time.

PMID- 9281235
TI  - [Functional insulin therapy and pregnancy].
AB  - Pregnant type-I diabetic women have to be treated in an experienced diabetes
      center where optimal cooperation and exchange of knowledge between obstetrician,
      diabetologist and neonatologist is guaranteed. Given optimal preconceptional
      metabolic control and thorough guidance throughout pregnancy maternal and fetal
      risk of type-I diabetic patients without severe diabetic late complications is
      similar to that of healthy pregnant women. "Near-normoglycemic" metabolic control
      and meticulous prevention of severe and long-standing hypoglycemic episodes can
      be achieved throughout pregnancy by functional insulin therapy employing a basis
      bolus regime of insulin administration with frequent blood glucose self control
      (more than 6 times a day). Non-compliant diabetic patients and those with severe
      diabetic late complications represent a high-risk group for complications in
      pregnancy. To avoid such risks special care and preconceptional information is
      mandatory.

PMID- 9281237
TI  - [Risks and side effects of intensified insulin therapy].
AB  - Diabetes mellitus may be accompanied by severe long-term microvascular,
      neurological and macrovascular complications. Prevention of these complications
      represents an enormous challenge for the diabetic patients and their doctors.
      However, if diabetic long-term complications occur, affecting one or more organ
      systems, it is a major goal to prevent their progression. Both, primary and
      secondary prevention require a good metabolic control striving for near-normal
      blood glucose values. Intensified insulin therapy (three or more daily injections
      or external insulin pump) has been shown to achieve a glycemic control as close
      to the normal range as possible.

PMID- 9281238
TI  - [Interventional endoscopic therapy of chronic pancreatitis].
AB  - BACKGROUND AND AIM: Complications in chronic pancreatitis, such as duct occlusion
      due to stenosis or stones can be treated by interventional endoscopic procedures.
      The benefit of such procedures and the effect on the clinical course is still
      under debate. Therefore, it was the aim of this study to analyze the effect of
      endoscopic interventional procedures in more detail with respect to technical and
      clinical benefit. PATIENTS AND METHODS: 100 patients with chronic pancreatitis
      (cP) were studied retrospectively. In 58 patients an indication for
      interventional endoscopic therapy was given (45 +/- 12 yrs; 46 M, 12 F; cP 1
      degree: n = 1, cP II degree: n = 8, cP III degree: n = 49). The patients were
      allocated to three groups: stenosis (n = 18), pancreatic duct stones (n = 18) and
      stenosis and pancreatic duct stones (n = 20). In two patients no visualization of
      the main pancreatic duct was performed due to cholestasis that was treated
      primarily. In total, 295 endoscopic procedures were performed (EPT, duct
      dilatation, plastic endoprothesis, ESWL, mechanical lithotripsy). Technical
      success was 95%. All stenoses could be dilated or bridged by plastic stents.
      Fragmentation of main pancreatic duct stones was achieved in 92%. The overall
      complication rate of all 319 endoscopies (fever, bleeding, stent dislocation) was
      15.8%. Five patients had to undergo surgery, however, not as a direct consequence
      of complications from or unability of endoscopic procedures. 86% of the patients
      reported complete pain relief after the endoscopic-interventional procedures and
      62% during the follow-up interval (7.4 +/- 6.3 months). 59% of the patients with
      weight loss and 58% of the patients with initially stable weight experienced a
      weight gain following endoscopic-interventional therapy. Individual patients
      showed improvement of endocrine or exocrine pancreatic function. 82% of the
      patients did not require inhouse treatment or emergency admission to the hospital
      whereas three admissions on average were recorded prior to endoscopic
      interventional treatment. Therefore, we conclude that a subset of patients does
      benefit from endoscopic interventional therapy of complications of chronic
      pancreatitis. However, a controlled prospective study is still mandatory.

PMID- 9281239
TI  - [Do ultrasound parameters allow diagnosis of biliary sphincter of Oddi
      dysfunction?].
AB  - A noninvasive test to prove sphincter of Oddi dysfunction is desired, because
      endoscopic manometry is technically demanding and not without risks. METHODS: 40
      consecutive patients (n = 20 patients with, and n = 20 patients without enzymatic
      cholestasis) with suspected SOD were investigated both by ultrasonography (US;
      3.5 MHz) and by endoscopic manometry. SOD was suspected at US if the extrahepatic
      bile duct diameter was > or = 9 mm and a further increase (at least > 0.5 mm) was
      observed after intravenous ceruletide (0.3 micrograms/kg b.w.). SOD was verified
      manometrically by a sphincter of Oddi basal pressure > or = 40 mmHg. Endoscopic
      sphincterotomy was performed if SOD was diagnosed by manometry. Thereafter, all
      patients were enrolled in a prospective follow-up (median: one year). RESULTS: At
      US SOD was suspected in eleven of 20 patients with cholestasis. SOD was confirmed
      manometrically in all of them but also in two further patients (13 of 20 patients
      with proven SOD). After EST twelve of 13 patients remained free from biliary
      symptoms. In the 20 patients without cholestasis SOD was suspected at US in five
      patients only. However, endoscopic manometry revealed SOD in eleven of 20
      patients and proved sonographically presumed SOD in only three of five patients.
      After EST only three of eleven patients remained asymptomatic during follow-up (p
      < 0.05 vs. patients with cholestasis). Clinically important side effects were not
      observed after ceruletide administration, whereas postmanometry pancreatitis was
      observed in three of 40 patients. CONCLUSION: In patients with recurrent symptoms
      after cholecystectomy and enzymatic cholestasis SOD was reliably diagnosed by
      ultrasonography (sensitivity: 85%, specificity: 100%), and this finding may guide
      endoscopic sphincterotomy.

PMID- 9281240
TI  - [Argon plasma coagulation in endoscopic therapy of CREST syndrome associated
      upper gastrointestinal hemorrhage].
AB  - We report on the case of a 55-year-old patient suffering from progressive
      systemic sclerosis (PSS). The patient was sent to our department when clinical
      symptoms of an acute upper gastrointestinal hemorrhage occurred. Upper endoscopy
      showed a watermelon stomach and fresh blood in the stomach. The presence of
      teleangiectasias in the antrum could be proved histologically. Since the
      teleangiectasias found in the antrum were the only possible source of the
      hemorrhage three sessions of endoscopic argon plasma coagulation were performed.
      Macroscopically, a nearly complete disappearance of teleangiectasias could be
      achieved. After a follow-up of six months, there have been no clinical signs of
      another hemorrhage episode. This case shows that the existence of
      gastrointestinal teleangiectasias should be considered when chronic anemia or
      acute gastrointestinal hemorrhage occur in patients with PSS. Further it is
      demonstrated that even extended gastrointestinal teleangiectasias can be
      successfully treated by endoscopically performed argon plasma coagulation.

PMID- 9281241
TI  - [Tumor suppressor gene p53--function and significance in gastroenterology].
AB  - The p53 gene is a tumor suppressor gene. The encoded p53 protein directly induces
      the expression of genes that are involved in cell cycle regulation. p53 was named
      "guardian of the genome" for its prevention of an otherwise fatal outcome under
      DNA damaging conditions. Under these conditions p53 inhibits cell cycle
      progression or induces apoptosis. The p53 protein has been structurally and
      functionally divided into four domains, two of which are of crucial importance:
      The sequence specific DNA-binding domain and the aminoterminal transactivation
      domain. They are both required to trigger the downstream processes following p53
      expression. Mutations and inactivation of p53 by oncogenes are frequent events in
      the development of human neoplasia. That includes gastrointestinal tumors with
      their mutational spectra reflecting tissue-specific influences of endogenous and
      exogenous factors in carcinogenesis. Despite considerable progress in molecular
      biology, clinical applicability of p53 in both diagnostic and therapeutic
      strategies has not yet been validated.

PMID- 9281242
TI  - [Transjugular intrahepatic portasystemic shunt (TIPS)--indications and outcome].
AB  - The use of the use of the transjugular intrahepatic portosystemic shunt (TIPS)
      and its indication for treatment of the various symptoms of portal hypertension
      is till under debate. This paper presents guidelines for its application based on
      randomized studies, case reports, and own experience. TIPS is indicated in acute
      variceal bleeding not responding to endoscopic treatment and medication. In this
      emergency situation TIPS has probably a lower early mortality rate than surgical
      shunts. The prophylactic treatment of first variceal bleeding is a domain for
      medical therapy. Due to its increased incidence of hepatic encephalopathy TIPS
      may only be indicated in very selected cases with a high risk of bleeding and
      associated severe complications. Five randomized trials including 402 patients
      exist comparing endoscopic treatment and TIPS. Except one study the results are
      conclusive demonstrating comparable survival of the groups. Despite these
      results, in view of the high rate of shunt-induced encephalopathy with its
      negative effect on life quality, TIPS may better be a secondary treatment as long
      as studies on life quality are lacking. However, im many patients additional
      complications, e.g., accompanying ascites or intolerance to bleedings, may
      justify the primary use of TIPS. TIPS is also effective in the treatment of
      refractory ascites. Conclusive randomized studies are not available, therefore,
      TIPS should be restricted to patients who are intolerant to or who fail
      paracentesis. In addition to the leading indications mentioned, rare indications
      for TIPS and the role of surgical shunts are discussed.

PMID- 9281243
TI  - [Immune function in the early stage of acute pancreatitis].

PMID- 9281245
TI  - [Drug-induced esophagitis: can stringent indications help prevent this disease
      picture?].

PMID- 9281244
TI  - [Lymphadenectomy in treatment of stomach carcinoma].

PMID- 9281252
TI  - [Significance of stem cell-supported high-dose chemotherapy in the treatment of
      gynecological malignancies: indications and current clinical trials in the
      Federal Republic of Germany].
AB  - The use of hematopoetic growth factors and stem cell support reduces the dose
      limiting hematopoetic toxicity's, resulting in a remarkable increase in dose
      intensity of chemotherapy. As far as data from phase I/II trials are available
      high dose chemotherapy (HDC) may be integrated in the systemic treatment of
      breast and ovarian cancers. In metastatic breast cancer HDC may induce fairly
      high but short response rates. Long term survival is expected in 20% of the
      cases. Patients with limited metastatic disease, without significant prior
      chemotherapy, partial or complete response to induction chemotherapy and complete
      remission after HDC may benefit from HDC. In phase I/II trials HDC improved
      recurrence free survival in high risk patients (e.g. > 9 positive LN) compared to
      historic controls and may therefore be a curative approach. Ovarian cancer is
      very chemosensitive. Conventional chemotherapies induce multidrug resistance
      rapidly. Just as in breast cancer-Phase I/II trials demonstrated high response
      rates to HDC, which again were short of duration.

PMID- 9281253
TI  - [Rhesus prophylaxis--history and current status].
AB  - The varying symptoms of rhesus incompatibility were recognized and described
      approximately sixty years ago. Jorg Schneider, then at the Freiburg University
      Hospital in Germany, had been the very first investigator to perform rhesus
      prophylaxis in pregnant women. The exact date of this achievement is August 9,
      1963. One year later, Schneider could report on nine women, who-following
      delivery of a rhesus-positive child-did not develop rhesus antibodies during a
      subsequent pregnancy with a rhesus-positive fetus. Since the late sixties, rhesus
      prophylaxis has been an integral part of prenatal care in Germany. In the
      meantime, the role of ante-partum prophylaxis has also been established. Since
      the introduction of post-partum rhesus prophylaxis, fetal morbidity and mortality
      has been reduced by 90 percent.

PMID- 9281254
TI  - [Adjuvant CMF chemotherapy in patients with breast cancer--results on blood
      coagulation and fibrinolysis].
AB  - Breast cancer disease and as well as CMF-chemotherapy are associated with an
      increased risk for thromboembolic complications. There is evidence that effects
      on the hemostatic system may play an important role. To minimize the impact of
      tumor associated hypercoagulability, we choose to study CMF-associated effects on
      the hemostatic system within an adjuvant setting. Blood coagulation and
      fibrinolysis were examined before and 24 hours after intravenous application of
      CMF-therapy at 17 patients with breast cancer. 16 parameters of coagulation and
      fibrinolysis were studied. In a longitudinal analysis covering the complete 6
      month treatment period we found a decrease of thromboplastin time (TPZ) factor
      VII (FVII) and protein C antigen (PC Ag) and activity (PC Act). Clinically
      relevant pathological results and cumulative effects were observed only for PC Ag
      and Act, while the mean values of TPZ and FVII returned to pre-treatment levels
      after each course of treatment. These data suggest a potential impact of CMF
      chemotherapy on synthesis and activation of vitamin-K-dependent coagulation
      factors thus providing a possible explanation for the increased risk for
      thrombosis during CMF-chemotherapy.

PMID- 9281255
TI  - [Psychosocial acceptance of surgical interventions of the breast in oncological
      gynecology].
AB  - In a retrospective analysis of 197/600 women (33%) treated for primary breast
      cancer at the Department of Obstetrics and Gynecology at the University of
      Munster (1984 to 1994) the psycho-social acceptance of mastectomy vs. breast
      conservative treatment (BET) was evaluated. Mean age was 59 years (range, 31-87
      yrs.). BET was performed in 58% (n = 114), modified radical mastectomy (MRM) in
      42% (n = 83). Reconstructive surgery after MRM was performed in 40% (n = 33)
      either as primary procedure in 39% (n = 14) or as secondary procedure in 61% (n =
      20). In addition to somatic patterns, features of pre- and postoperative coping,
      individual psycho-social burden, cosmetic results, contentment of treatment,
      social rehabilitation and quality of life were evaluated. Performance status and
      quality of human relations are discussed. In terms of psycho-social acceptance
      the results of BET are in general not superior to MRM at a mean follow-up of six
      years. Coping and postoperative quality of life are almost similar within the two
      groups. Although the alteration of body image after BET is less compared to MRM,
      the psychologic burden of postoperative radiotherapy and the fear of local
      recurrence are experienced worst compared to all other features analyzed after
      BET.

PMID- 9281256
TI  - [Ultrasound-guided transvaginal puncture of ovarian cysts].
AB  - Ultrasound-guided transvaginal aspiration of ovarian cysts offers a simple
      outpatient strategy for immediate pain relief and effective treatment but bears
      the risk of an iatrogenic spread of malignant cells. This study evaluated the
      cellular composition of the cyst fluids in a group of 26 sterility patients, in
      all of whom one or more ovarian cysts had been diagnosed and punctured. None of
      the patients had complications or evidence of malignant cells on cytological
      examination after the puncture. Only in one case dyskariotic cells were diagnosed
      causing an operative exploration that revealed a benign tumour. In 9 patients the
      ovarian cysts recurred and therefore 2 patients finally underwent an exploratory
      operation. In our opinion transvaginal ultrasound aspiration of functional cysts
      is an easy and safe procedure and may be undertaken in sterility patients in the
      context of specific criteria.

PMID- 9281257
TI  - [Hormone substitution following transcervical endometrial ablation].
AB  - The transcervical endometrium ablation is more and more used for the treatment of
      therapy refractory bleeding disorders. Since in 70% of the patients, even with a
      postoperative amenorrhoea, a residual endometrium can be found a hormone
      replacement therapy should in any case include a sequential or continuous
      application of progestagen. For the prevention of a hematometra by using a
      hormone replacement therapy the cervix should be spared during endometrium
      ablation. With recurrent therapy-refractory bleeding disorders during hormone
      replacement therapy an indication for endometrium ablation can also be given. In
      these patients a postoperative amenorrhoea can be reached by a continuous hormone
      replacement therapy.

PMID- 9281258
TI  - [Hygroma colli (cervical neck edema) as an ultrasonographic parameter of fetal
      chromosome anomalies].
AB  - A two year retrospective study of 57 women with fetal hygroma colli between 2 and
      15 mm was carried out at the University Women Hospital in Heidelberg. In this
      study maternal age, week of gestation, thickness of the nuchal oedema and the
      genetic results of amniocentesis were documented. Chromosomal abnormalities were
      found in 20 cases (35%), monosomy X in eleven, trisomy 21 in five and trisomy 18
      in four. No connection between an individual syndrome and a particular week of
      gestation could be found. An increase of the thickness of the nuchal oedema
      showed a significant correlation to the incidence of aneuploidies. Chromosomal
      abnormalities were not observed in cases of less than 3 mm thickness (0/5).
      Between 3 and 4.9 mm one abnormal karyotype (4 mm) was found (1/18) whereas in
      the group of 5-6.9 mm approximately one third (6/15) of all fetuses showed
      chromosomal abnormalities. Aneuploid karyotypes were found in two thirds of cases
      (14/20) with a fetal nuchal translucency of 7 mm and more. Surprisingly, a
      correlation between maternal age and incidence of fetal chromosomal abnormality
      could be seen, but it was not significant. While a chromosomal aberration could
      be connected to age in 50% of mothers under the age of 25 and over 34, only a
      third of women aged 25-29 and only one fifth aged 30-34 showed chromosomal
      abnormalities in combination with hygroma colli. Our results confirm the
      recommendation of previous studies for extensive ultrasound examination during
      the first and second trimester in order to improve early detection of fetal
      chromosomal abnormalities particularly in women not normally covered by the age
      related indication for amniocentesis.

PMID- 9281259
TI  - [Primary dedifferentiated leiomyosarcoma of the fallopian tube].
AB  - Between 1960 and 1995 the University of Leipzig Women's Hospital encountered 44
      cases of primary malignant tumors of the Fallopian tube, including four malignant
      Muller mixed tumors and one sarcoma. The sarcoma, a dedifferentiated
      leiomyosarcoma, was found incidentally in a 57-year-old woman. Treatment
      encompassed total abdominal hysterectomy and bilateral salpingo-oophorectomy with
      omentectomy and pelvic and para-aortic lymph node dissection, followed by
      telecobalt irradiation of the pelvis (Hd 52 Gy). One year after treatment, no
      evidence of disease recurrence, is found. Literature documents only 34 cases of a
      primary uterine tube sarcoma. Even with RO-resection, the early, high rate of
      local recurrence (most often within the first two years after treatment) and
      hematogenous metastasis to the lungs, liver and bones compose this tumor's
      clinical course. The prognosis is poor despite the use of radiotherapy and/or
      combination chemotherapy.

PMID- 9281260
TI  - [Ovarian Leydig cell tumor].
AB  - A case report on a 73 year old woman with an Leydig cell tumor of the right ovary
      accidentally discovered after hysterectomy with bilateral salpingo-oophorectomy
      is given. Signs of virilization existed for many years, but no diagnostic
      investigations had been performed. Histologically a well-differentiated Leydig
      cell tumor was found as the reason of the androgenic changes which regressed
      after extirpation of the tumor.

PMID- 9281261
TI  - [Futile intra-amnion Rivanol administration and prostaglandin labor induction in
      uterus unicornis unicollis with a noncommunicating right-sided horn].
AB  - We report on the futile use of labour-inducing agents in a patient with a
      Mullerian duct abnormality. In the 20th week of gestation, foetal death had been
      diagnosed in the rudimentary right horn. It is suggested that induction as well
      as continuation of effective contractions depends on the intact uterus (cervix,
      lower uterine segment, and corpus).

PMID- 9281262
TI  - [Chronic ascending encephalomyelitis of herpetic etiology (a clinico
      morphological study)].

PMID- 9281263
TI  - [The paradoxical regulation of growth hormone release in syringomyelia patients].

PMID- 9281264
TI  - [The effect of enkorat on the course of epilepsy in children].

PMID- 9281265
TI  - [The effect of verbal reinforcement on visual-space perception in chronic
      alcoholism].

PMID- 9281266
TI  - [The problems of borderline psychiatry in English medicine of the 16th-18th
      centuries].

PMID- 9281267
TI  - [Modern concepts of the pathogenesis of phakomatoses].

PMID- 9281268
TI  - [The structure and permeability of the hemato-encephalic barrier and the
      prospects for drug delivery across it].

PMID- 9281270
TI  - [The classification of the late period in closed spinal trauma].
AB  - 154 patients in the late period of closed trauma of spinal cord were followed up,
      40 patients were examined by means of MRT method. There was a progredient course
      of disease in 20.3% of cases, mainly in patients with compression of spinal cord.
      The main syndromes of the late period of disease, which was usually characterised
      by progressive course, were limited adhesive process (arachnoiditis) or
      progressive myelopathy. The latter manifested with myelomalacia, atrophy, cystic
      spinal cord's degeneration, discirculatory myelopathy. The classification of the
      late period of spinal trauma was elaborated. It is of essential importance for
      medical and social rehabilitation of patients.

PMID- 9281269
TI  - [Hereditary spastic paraplegias: a comparative study of Russian populations].
AB  - 15 families (27 patients) with hereditary spastic paraplegia (HSP) were found in
      the course of monogenic disorders investigation in 6 Russian populations. High
      HSP prevalence (7.21+1.61) x 10(-5) was found in Kirov Province [the frequency of
      the gene of autosomal-dominant form was (3.61 +/- 1.14) x 10(-5), autosomal
      recessive-(64.5 +/- 9.74)- 10(-6)]. The pronounced interfamilial polymorphism of
      HSP was observed. Two families with rare autosomal-recessive variation of "clear"
      HSP as well as two families with HSP associated with peroneal amyotrophies were
      revealed. Accumulation of cases with unusual combination of autosomal-dominant
      HSP together with mental deficiency was remarkable in Kirov Province.

PMID- 9281271
TI  - [Chronic inflammatory demyelinating polyneuropathies].
AB  - A chronic inflammatory demyelinating polyneuropathy (CIDP) is described both on
      the basis of authors' own observations and literary data. The disease is
      characterised by delayed onset with progredient, progredient-remittent and stable
      course of flaccid paresis of extremity together with mild distal sensitive
      disturbances, albumino-cytologic dissociation and dysimmunoglobulinemia. Cranial
      nerves damages and vestibulo-cerebellar disturbances were observed in a number of
      patients. This confirms the involvement of CNS in CIDP. The common character of
      clinical, immunological, laboratory and electrophysiological findings permits to
      consider CIDP and Guillain-Barre syndrome as autoimmune diseases. Meanwhile some
      recent findings on the formation of antibodies to peripheral nerves structures as
      well as high titers of antisulfamide and antigangliosides antibodies permit to
      suggest CIDP as separate nosological unit. Additional clinical data and the
      evaluation of the role of etiological and pathogenetic mechanisms are necessary
      for the final conclusion.

PMID- 9281272
TI  - [Clinico-pathogenetic variants of the piriform muscle syndrome].
AB  - The method of diagnosis of pathogenetic variations or musculus piriformis
      syndrome (MPS) by means of computer tomography is described. 24 patients with
      early signs of lumbar osteochondrosis and MPS were examined. Two variations of
      MPS with specific clinical and tomographic features were revealed, namely: an
      early spastic (functional) type and degenerative-dystrophic one. The
      peculiarities of muscles (diameter, location, density) and of adjacent pelvic
      structures were investigated in 15 healthy controls. Differentiated treatment of
      MPS permitted to control the pain and to promote other clinical signs regression
      faster than conventional therapy.

PMID- 9281273
TI  - [The restoration of the sensitive function of the nerves in replanted upper
      extremities].
AB  - The investigation of both dynamics and peculiarities of restoration of sensitive
      functions of radial, ulnar and median nerves was performed in terms of dependence
      upon the time after trauma in 76 patients which underwent replantation of large
      upper limbs' segments associated with traumatic amputation. Some delay behind was
      revealed in restoration of ulnar nerve's sensitive function during the second and
      the third half-years after operation as compared with radial and median nerves'
      functions. These differences disappeared one and a half-two years after trauma.
      It is necessary to take this into consideration. In of rehabilitation on the
      patients either with new traumas or after replantation of large segments of upper
      limbs.

PMID- 9281274
TI  - [The function of the hypothalamo-hypophyseal-gonadal system in patients with
      Friedreich's ataxia].
AB  - Both the decrease of reproductive adaptation and effect of reproductive
      compensation were revealed in 19 cases of Friedreich's ataxia (FA). Retardation
      of sexual development was observed, the degree of which correlated with the age
      of disease manifestation. By means of radioimmunoassay basal and stimulated
      secretion of hypophysial and peripheral sex hormones were examined in 6 males and
      9 females (17-30-years). The gonadal hypofunction was observed as the consequence
      of hypothalamo-hypophysial insufficiency. The decrease of follicle stimulating
      hormone and prolactin levels was found. The conclusion was made that pathological
      process in FA involves hypothalamus that causes in turn insufficiency of
      norepinephrine and epinephrine hypothalamic neurotransmission.

PMID- 9281275
TI  - [The syndrome of drive pathology in children and adolescents (the age-related and
      nosological aspects)].
AB  - 43 children and adolescents, 27 boys and 16 girls aged 7 to 15, with the drive
      disorders syndrome were investigated. The diagnosis of schizophrenia was in 30
      patients (the first group), residual organic brain damage in 13 (the second
      group). In the first group an onset of disease coincided with the first age
      crisis (3-4 years). Among the variants of the drive disorders such disorders as a
      runaway from home and wandering, that had irresistible and impulsive character
      were dominant. Near the puberty, the sexual and aggressive-sadistic drives
      prevailed. The drive disorders were accompanied with effective, neurotic-like and
      some other psychopathological symptoms. In the second group the first
      manifestations of the drive disorders coincided with the young school-age (7-9
      years) period and these disorders occurred in the prepuberty (10-12 years) more
      frequently. The drives to the theft, runaway from home and wandering, aggression,
      increased sexual drive were dominant. The signs of psychic infantilism and
      immature emotional-will sphere come forward in the patients on this group. It was
      determined that inherited-constitutional as well as social factors are very
      significant for formation of the drive disorders syndrome.

PMID- 9281277
TI  - [Clinical computed tomographic correlations in children from a group at high risk
      for schizophrenia].
AB  - Computed tomography (CT) was performed in 189 individuals: in 44 children of
      schizophrenic parents (high risk group, HRG), in 39 parents with schizophrenia or
      with schizophrenic disturbance, in 56 children with schizophrenia, in 50 children
      with consequences of early organic damages of central nervous system (mental
      retardation syndrome and generalized tic syndrome). The frequency of CT changes
      was equal in the mentioned groups but their character was quite different. The
      widening of brain's liquor system (89.7%), the signs of frontal and temporal
      atrophia (31%), foci of decreased density of cerebral brain's matter, closer in
      subcortical ganglia and periventricular zone, and different anomalies of brain
      were observed in HRG children.

PMID- 9281276
TI  - [Mental disorders in patients who abuse homemade opiates].
AB  - 194 male patients with narcomania caused by home-made opiates' abuse were
      observed. The age of patients was 18-45 years, narcotization period lasted 3-22
      years. In all the patients psychopathological symptoms were observed during all
      stages of disease. There were both affective and psychopathic-like disorders as
      well as the changes of personality. The psychic disorders were especially
      pronounced in the acute period of abstinence syndrome but were also observed
      during the remote stages of disease as well as during remission. There were
      different variations and types of affective disorders in different stages of
      disease. The two types of remissions were recognised with prevalence of
      depression at the first type and emotional lability and psychopathy at the
      second. The formation of psychopathic-like defect was quite typical for this type
      of opiate narcomania.

PMID- 9281278
TI  - [Debatable issues in the problem of somatoform and related disorders].
AB  - The questions of including into ICD-10 and DSM-III-R of extranosological category
      -somatoform disorders is discussed. Some positive moments were considered, but
      inexpediency of the limitation of somatoform disorders to psychological
      disturbances only, doubtfulness of both including psychosomatic diseases in this
      category and age limitations in beginning and duration of the disease were
      stressed. The concept of somatopsychic diseases was proposed with three main
      variations: 1) with relatively independent rise of somatic and psychic disorders,
      2) with prevailing etiopathogenic role of psychic factor (psychosomatic
      disorders, somatized psychic disturbances, somatoform neurotic and psychosomatic
      disturbances), 3) with prevailing etiopathogenic role of somatic factors
      (somatogenic psychic disorders). The actual distribution of somatopsychic
      disturbances are presented on the syndromal, nosologic and personal levels using
      data of prophylactic medical examination of one big enterprise's employees.

PMID- 9281279
TI  - [The effect of low doses of nakom on the hormonal secretion of the hypothalamo
      hypophyseal-adrenal system in patients with infantile cerebral palsy].
AB  - The levels of hormones of hypothalamo-hypophyseal-adrenal system were measured in
      14 10-14 year old children with infantile cerebral paralysis (ICP) with central
      catecholaminergic motor insufficiency. Contents of adrenocorticotropic hormone
      (ACTH), hydrocortisone (HC), somatotropic hormone, prolactin (P) were examined
      before and during Nacome administration (62.5 mg once daily in the morning). 110
      patients of the same age with ICP and 18 children with acquired encephalopathy
      (EP) formed the control group. The elevations of ACTH, HC and P were revealed in
      spastic forms of ICP. Meanwhile nearly normal hormonal levels were observed in
      hyperkinetic forms of ICP and EP. The more pronounced effect was noted in
      "dopamine-dependent" children in which the drug's administration resulted in
      normalization of clinical and biochemical indices. Hyperkinetic phenomena
      revealed the connection between the character of neuromotor dyskinesias and the
      state of hypothalamo-hypophyseal-adrenal axis which is regulated by dopamine. The
      data obtained show hypofunction of dopaminergic neurotransmitter cerebral systems
      in patients with ICP that plays important pathogenetic role in development of
      disease with systemic manifestations.

PMID- 9281280
TI  - [The use of the amitriptyline analog amizol in depressions].

PMID- 9281281
TI  - [The psychophysiological aspects of treating obesity with Izolipan].
AB  - 20 patients with obesity were examined. Their weight was increased as compared
      with ideal values by 30-140%. The patients were characterized by anxious or
      depressive disturbances (Spilberger's and Beck tests) and alterations of
      alimentary behaviour in form of prevalence of emotional and external alimentary
      behaviour (EMAB and EAB, respectively). The study of cognitive negative
      variations (CNV) revealed the decrease of late wave's area, which correlated
      reversely with levels of anxiety, depression and EMAB expression. The Isolipan
      administration (15 mg, 2 times/daily during 3 months) together with hypocaloric
      diet resulted in average weight loss equal to 12.3 kg in the whole group. These
      changes correlated well with normalization of both alimentary behaviour (in the
      form of decrease of EMAB and EAB indices) and emotional state, and increase of
      decreased late CNV with disappearance of pathological psycho-physiological
      correlations between CNV and emotional state.

PMID- 9281282
TI  - [The neuromotor functional status of patients with circulatory encephalopathy].
AB  - The aim of this study was to reveal the secondary neuromuscular disorders in 104
      patients with spondylogenic discirculatory encephalopathy and to study the
      influence of different methods of combined physiotherapy (laser irradiation,
      troxevasin vacuum-phonophoresis, vacuum-message) on dynamics of
      electroneuromyographic (ENMG) indices. The application of electroneuromyography
      (ENMGST-01 apparatus) permitted to establish that pathological neurophysiological
      phenomena developed in patients progrediently and were qualitatively unstable. It
      was also determined that combined usage of laser-photobiostimulation and
      troxevasin vacuum-phonophoresis promoted more steadfast liquidation of
      neurological signs of the disease as well as the improvement of functional state
      of neuromotor system. Moreover, the usage of combined ENMG methods significantly
      contributed to understanding of pathological processes underlying the evaluated
      neurophysiological syndromes. The authors made the conclusion about high
      effectiveness and good perspectives of craniocaudal coefficient's application for
      determination of correlations between clinical state of patients and diagnostic
      tests' data.

PMID- 9281283
TI  - [The electrophysiological diagnosis of carpal tunnel syndrome].
AB  - Electrophysiological investigations were carried out both in patients with carpal
      tunnel syndrome (CTS) and in healthy individuals. The evoked potentials were
      examined during stimulation of sensitive branches of n. medianus and of other
      nerves. The most sensitive and important for diagnosis appeared to be the
      electrophysiological test of alteration of responsive reaction to the stimulation
      of the sensitive branch of n. medianus for 4 finger and the considerable
      difference of evoked reactions on stimulation of skin palm branch and branch of
      the 1-st finger of n. medianus. The diagnostic importance of these indices
      corresponds well to anatomical and pathophysiological characteristics of CTS.

PMID- 9281284
TI  - [Autoantibodies to brain tissue antigens in epilepsy patients].
AB  - The observation of 38 patients with different forms of epilepsy was carried out
      in terms of autoantibodies (aAB) to nervous tissue proteins: p16, p30 and S-100.
      The pathological increase or decrease of aAB titers to at least one of the
      antigens (AG) mentioned above was found in 31 cases. The qualitatively new
      approach was further used for the revelation of aAB to S-100. Not the very
      protein was adsorbed on the plates for immunoenzyme assay but antiidiotypic Abs
      which were the "mirror reflection" of corresponding protein molecules'
      determinants. The authors suggested that the method permitted to estimate the
      level of aAB to the whole complex of AG determinants. Thus, the percent of
      positive tests was approximately twice higher. The index of aAB binding by
      corresponding anti-idiotypes was decreased in 29 patients. It's quite possible
      that it formed some conditions for brain tissue damages by aAB.

PMID- 9281285
TI  - [Antibodies to brain galactocerebrosides in the serum and cerebrospinal fluid of
      patients with disseminated sclerosis].
AB  - The titers of antibodies (AB) to myelin's glycolipids galactocerebrosides (GC) as
      well as some other immunological indices were measured in 63 patients with
      multiple sclerosis (MS), in 14 patients with other similar neurological diseases
      and in 9 individuals with cerebellospinal ataxias. The correlation between the
      frequency of revelation of high serum AB titers and MS stage was observed. Thus
      the highest frequency was observed at primary progredient current of MS and at
      decline of its aggravation while the latter was found in steady remission. The
      correlation between level of AB to blood serum GC and blood immune complexes
      concentrations (complement and antistreptolysin O) was established too. Meanwhile
      these were not bound in patients with cerebellospinal ataxias and with other
      neurologic diseases or the titers of AB to GC were quite low in such cases. The
      titers of AB to GC in liquor were rather high in 2 patients with MS and in 1
      patient with viral encephalitis while there were no AB to GC in other cases. That
      may be caused by determination of immunoglobulins of M class in reactions of
      complement binding. The determination of AB to GC in blood serum may be quite
      usefull in differential diagnosis of MS and other similar clinical conditions.

PMID- 9281286
TI  - [Neurotransmitter changes in amyotrophic lateral sclerosis].
AB  - The results of investigation concerning both total and cerebral catecholamine
      metabolism indices in 78 patients with amyotrophic lateral sclerosis (ALS) are
      presented. The considerable elevation of both blood and liquor norepinephrine
      level as well as of blood epinephrine concentration was observed together with
      acute decrease of platelet MAO B activity. The conclusion was made about the
      participation of catecholamines in exitotoxic mechanisms of motor neurons systems
      death which was quite characteristic for ALS development. A short literary review
      was presented concerning the role of neurotransmitters in regulation of motor
      functions. The neurochemical disturbances which may result in release of
      exitotoxic mechanisms of ALS were considered too. The consideration of data
      obtained as well as the analysis of modern conceptions of ALS pathogenesis enable
      both to determine some ways of ALS pathogenetic therapy and to define the basic
      directions of further investigations.

PMID- 9281287
TI  - [The system of psychiatric care in Canada (the province of British Columbia)].

PMID- 9281289
TI  - [The Russian antidepressant tetrindole].

PMID- 9281291
TI  - [Neuropathy of the superior cutaneous nerve of the ischium].

PMID- 9281290
TI  - [Pediatric absence epilepsy].

PMID- 9281288
TI  - [The problem of the "settlement" of the mentally ill elderly in psychiatric
      hospitals].
AB  - The gerontopsychiatric contingent of long-term stayers (LTS) (the patients who
      had permanently continued to stay in hospital for more than 5 years) was studied
      in two mental hospitals of Tver Province. There were 27.6% and 20.2% of LTS cases
      of overall geriatric contingents in these hospitals which included the patients
      older than 60 years old. The study covered different demographical, clinical and
      social aspects of this problem. In both groups it was established that more than
      half of the patients suffered from chronic schizophrenia (in the state of
      hallucinatory-delusional psychosis or in schizophrenic defect). The residual
      organic defect prevailed in the remaining patients. The factor furthering a long
      term stay in hospitals was unfavorable social status of patients, namely most of
      the patients were lonely, more than half of them hadn't got any own habitation.

PMID- 9281292
TI  - [Leprosy and infection by the human immunodeficiency virus (HIV)].

PMID- 9281293
TI  - [Evaluation of the campaign against leprosy in Tunisia].

PMID- 9281294
TI  - [Survey of leprosy disabilities in patients treated with multiple drug therapy in
      Ivory Coast].
AB  - Between 1990 and 1995, twenty thousand cases of leprosy were treated with WHO
      recommended multiple drug therapy (MDT) in Ivory Coast. A disability survey was
      conducted in April 1996 with a half-randomized sample of five hundred patients.
      This survey showed that 28.73% of the patients had got grade two disabilities in
      WHO scale. 12.9% of the non disabled patients at detection had developed leprosy
      impairments during or after treatment. Plantar ulcers (12.2% of the patients)
      appeared very frequent comparatively to the findings of a similar survey in
      Burkina Faso in 1995 (0.9% of plantar ulcers). With these results, the authors
      estimated the needs for disabilities care to enable the reinforcement of the
      prevention of disabilities and physical rehabilitation (POD and PR) in Ivory
      Coast.

PMID- 9281295
TI  - [Simplification and codification of treatment for leprous plantar ulcers].
AB  - Practically leprous plantar ulcers (PU) are difficult to treat and heal under
      field condition. Considering the important number of patients showing a PU, the
      directors of national leprosy control programmes are determined, within the
      programmes on prevention of disabilities (POD), to treat the PU in the field.
      Therefore it appears to be essential to codify and simplify their treatment thus
      enabling it to be effective. The healing of PU being the only criteria of
      effectiveness of the technique. Four clinical stages were defined, each
      corresponding to a precise way of treatment using only essential and basic
      products at low cost. During the trainings about the treatment techniques and
      attitudes much emphasize is given on the discharge of the PU, on the trimming of
      the wound and on the products to use according to PU's evolutionary stage.

PMID- 9281296
TI  - Biological Significance of Mono- ADP-ribosylation in Animal Tissues. Proceedings
      of an international workshop. Hamburg, Germany, May 19-23, 1996.

PMID- 9281297
TI  - [The frequency of various types of disk displacement and its relation to
      occlusion].
AB  - The aim of this study is to observe the frequency of the different types of disc
      displacements (d.d.) of the TMJ (ATM) and to evaluate if these types are related
      or not with malocclusions. One hundred patients and 13 asymtomatic volunteers
      underwent full clinic examination. sagittal MRI (mouth open and closed) and
      coronal MRI (mouth closed). The different types of disc displacements were noted
      and cumulated in frequency and in relation with several occlusal criteria. Unlike
      the general opinion stating that the antero-medial d.d. (d.d. a-m) are the most
      frequent amongst the internal derangements, the result of this study reveals that
      the antero-lateral d.d. (d.d. a-l) are more frequent amongst the patients (35.1%)
      and the asymptomatic volunteers in general and particularly in view of a
      malocclusion (exagerated anterior overlapping and posterior cross bite). The
      study gives rise to the question of the etiology of a antero-lateral d.d. and
      sets back the hypothesis of the lateral pterygoid muscle fundamental role in the
      disc displacements.

PMID- 9281299
TI  - [Is it necessary to reform the laws of compensation in the matter of medical
      professional responsibility?].

PMID- 9281298
TI  - [Necrotizing sialometaplasia: apropos of a case and review of the literature].
AB  - Necrotizing Sialometaplasia is an inflammatory, self-healing, reactive process of
      probable vascular origin, that most commonly involves the minor salivary glands
      of the palate but can bee seen in all salivary glands. As its clinical and
      pathological features may suggest malignancy, knowledge of histologic criteria
      indicating the benign nature of the lesion and the integration of clinical and
      pathologic elements are required to obviate this mistake. We review the
      literature reporting to one case.

PMID- 9281300
TI  - Vector autoregressive modeling for analyzing feedback regulation between heart
      rate and blood pressure.
AB  - We present a noninvasive technique for analyzing the feedback relationship
      between short-term fluctuations in blood pressure (BP) and heart rate (HR) in
      humans. Beat-to-beat BP was monitored for several minutes with a noninvasive BP
      measuring device, i.e., arterial tonometry, in 16 healthy subjects and 15
      patients on hemodialysis (HD), and the recorded systolic BP (SBP) and the pulse
      wave interval (R-R interval) were fitted to vector autoregressive models
      according to Akaike's method. The impulse-response function was then simulated to
      determine the contribution of changes in R-R interval or SBP to the fluctuation
      of SBP or R-R interval along a time scale. In healthy subjects, when a simulated
      1-mmHg impulse was applied to SBP, the R-R interval increased to approximately
      3.5 ms with a delay of several beats. In HD patients the same impulse caused
      essentially no response in the R-R interval. A 1-ms impulse applied to the R-R
      interval decreased SBP, and the response was not different in healthy subjects
      and HD patients. In the R-R interval-to-R-R interval response and the SBP-to-SBP
      response, the exponential-like decay after the initial jump was more rapid in the
      HD patients than in the healthy subjects. The results demonstrated that this
      technique can provide information on the feedback regulation between fluctuations
      in BP and HR in patients with or without autonomic nervous system dysfunction.
      This technique provides a simple and practical way to estimate autonomic function
      in clinical medicine.

PMID- 9281301
TI  - [Study of the bioequivalence of a new isosorbide dinitrate tablet formulation
      compared with the standard preparation].
AB  - An investigation in the bioequivalence of a new tablet formulation with 5 mg
      isosorbide dinitrate (CAS 87-33-2, ISDN 5 von ct) was performed in a two-way
      cross-over study with 18 subjects. The relative bioavailability with respect to a
      reference preparation for AUC related to isosorbide dinitrate was 107.5% and for
      Cmax 112.5%. A positive decision for bioequivalence derived from the usual
      confidence intervals for both parameters related to isosorbide dinitrate and the
      metabolites isosorbide-2-nitrate and isosorbide-5-nitrate, respectively. The
      difference in tmax showed no clinical relevance. The new formulation was
      bioequivalent to the reference.

PMID- 9281302
TI  - [Studies on the protective effect of lansoprazole on human gastric mucosa against
      low-dose acetylsalicylic acid. An endoscopic controlled double-blind study].
AB  - In a randomized double-blind parallel study the gastroduodenal tolerability of
      300 mg acetylsalicylic acid (ASA) daily has been evaluated in the presence of
      placebo, 15 mg lansoprazole (CAS 103577-45-3, Agopton) and 300 mg ranitidine
      daily (8 a.m.) in 30 healthy volunteers using upper gastrointestinal tract
      endoscopy. The treatment periods lasted 14 days. Endoscopic controls were
      performed at entry and repeated at day 14. At entry, the mean endoscopic score
      averaged 1.0 +/- 0.0 (+/- SEM) in the ASA/placebo (n = 10), in the ASA/
      lansoprazole 15 mg (n = 10) and the ASA/300 mg ranitidine group. In the placebo
      experiments 300 mg ASA daily induced marked gastroduodenal lesions at day 14
      (lesion score of 10.1 +/- 1.4) (+/- SEM). Concomitant administration of 15 mg
      lansoprazole daily offered significant protection against 300 mg ASA daily on day
      14 (3.6 +/- 1.2) (p < 0.05), 300 mg ASA plus 300 mg ranitidine daily reduced the
      damaging score to 5.8 +/- 1.3 (p n.s. vs ASA/placebo). Our data suggest that co
      administration of 15 mg lansoprazole daily reduces significantly gastroduodenal
      lesions evoked by 300 mg ASA.

PMID- 9281303
TI  - Transcription factors and the down-regulation of G1/S boundary genes in human
      diploid fibroblasts during senescence.
AB  - The hallmark of cellular aging is the failure of senescent cells to initiate the
      DNA synthesis during the progression of cell cycle. Since most, if not all, of
      the G1/S genes exhibit a significant down-regulation during aging, an alteration
      of gene regulation at late G1/S boundary could be a major contributing factor for
      the loss of dividing potential during cell senescence. The underlying cause for
      the apparent global attenuation of gene expression at late G1/S boundary is not
      clear. Since we have shown that thymidine kinase (TK) and dihydrofolate reductase
      (DHFR) are transcriptionally regulated during aging, we suspect that a similar
      mechanism may be operative in the age-dependent down-regulation of other G1/S
      genes. DNA binding activities using Y-box containing sequence in TK promoter or
      E2F containing sequence in DHFR promoter show prominent serum-responsiveness in
      low passage cells and dramatic attenuation in senescent cells. Promoter analysis
      using GCG program reveals striking similarities in promoter organization of
      twelve age-dependent G1/S genes. Specifically, these genes can be divided into
      two groups, one group contains tandem multiple CCAAT element, similar to that in
      TK promoter and the other contains E2F site, similar to that in DHFR promoter.
      Further analysis shows that the promoter of transcription factor, NF-Y, which
      recognizes CBP/tk site contains a tandem, two Y-box motif, similar to that in TK
      promoter and that the promoter of E2F1 contains four E2F motifs and two tandem
      CCAAT elements. Thus, these two important transcription factors could undergo
      autoregulatory control themselves. It is possible that regulation of only a few
      of transcription factors such as CBP/tk (NF-Y) and E2F1 may be sufficient to
      cause a global attenuation of most of G1/S genes in human diploid fibroblasts
      during senescence.

PMID- 9281304
TI  - In situ PCR. Overview of procedures and applications.
AB  - The evaluation of gene expression in the context of cellular morphology is
      essential to the full understanding of cell biology. A variety of methods for
      detection of nucleic acids are currently available. Solution PCR requires
      disruption of the sample and detection of the amplified material by
      electrophoresis in agarose gels. In situ Hybridization methods, on the other
      hand, permit morphological correlation and provide a high sensitivity that is
      sufficient for many applications. In some instances, however, the amount of
      target in the sample is below the limit of detection of this technique. In situ
      PCR allows the detection of minimal amounts of nucleic acids with exquisite
      sensitivity and specificity, while the integrity of the cells and the morphology
      of tissues remains preserved. This technique, although not exempt from
      difficulties, is undergoing methodological simplifications that will make it
      suitable for an increasing number of basic science and clinical applications. The
      following is a review of the principles, methods and applications of In situ PCR.

PMID- 9281305
TI  - Farnesol as a regulator of HMG-CoA reductase degradation: characterization and
      role of farnesyl pyrophosphatase.
AB  - We have recently reported that the isoprenoid compound farnesol accelerates
      degradation of the cholesterologenic enzyme 3-hydroxy-3-methylglutaryl coenzyme A
      (HMG-CoA) reductase, when added to cultured cells. We have thus proposed that
      farnesol is a required nonsterol regulator of this degradation event (T. E.
      Meigs, D. S. Roseman, and R. D. Simoni, 1996, J. Biol. Chem. 271, 7916-7922). In
      this report, we have studied the enzyme farnesyl pyrophosphatase (FPPase) in
      Chinese hamster ovary cells. We demonstrate that FPPase activity increases under
      conditions of increased metabolic flow through the isoprenoid pathway. Also, we
      show that a nonhydrolyzable analog of farnesyl pyrophosphate, an isoprenoid
      (phosphinylmethyl)phosphonate, inhibits FPPase in vitro, and when added to cells
      this inhibitor blocks the mevalonate-dependent, sterol-induced degradation of HMG
      CoA reductase. Furthermore, exogenous farnesol overcomes the effect of this
      inhibitor. These results suggest an isoprenoid-mediated regulatory mechanism
      governing intracellular farnesol production and support the hypothesis that
      farnesol is a nonsterol regulator of reductase degradation.

PMID- 9281306
TI  - Thrombin regulates interleukin-6 synthesis through phosphatidylcholine hydrolysis
      by phospholipase D in osteoblasts.
AB  - We previously reported that thrombin stimulates Ca2+ influx and activates
      phosphatidylcholine-hydrolyzing phospholipase D in osteoblast-like MC3T3-E1
      cells. In this study, we investigated the effect of thrombin on interleukin-6 (IL
      6) synthesis in these cells. Thrombin stimulated IL-6 synthesis dose-dependently
      in the range between 0.01 and 1 U/ml. The depletion of extracellular Ca2+ by EGTA
      suppressed the thrombin-induced IL-6 synthesis. TMB-8, an inhibitor of
      intracellular Ca2+ mobilization, also inhibited the IL-6 synthesis by thrombin.
      Propranolol, a phosphatidic acid phosphohydrolase inhibitor, enhanced the IL-6
      synthesis by thrombin. Calphostin C, a highly potent and specific inhibitor for
      protein kinase C, significantly amplified the IL-6 synthesis by thrombin. The
      thrombin-induced IL-6 synthesis was enhanced in PKC down-regulated MC3T3-E1
      cells. These results strongly suggest that thrombin stimulates IL-6 synthesis,
      which depends on intracellular Ca2+ mobilization mainly from extracellular space
      in osteoblasts, and that the IL-6 synthesis by thrombin is regulated due to
      thrombin-activated protein kinase C through phosphatidylcholine-hydrolyzing
      phospholipase D.

PMID- 9281307
TI  - Identification of the nonsubstrate steroid binding site of rat liver glutathione
      S-transferase, isozyme 1-1, by the steroid affinity label, 3beta
      (iodoacetoxy)dehydroisoandrosterone.
AB  - 3beta-(Iodoacetoxy)dehydroisoandrosterone (3beta-IDA), an analogue of the
      electrophilic substrate, Delta5-androstene-3,17-dione, as well as an analogue of
      several other steroid inhibitors of glutathione S-transferase, was tested as an
      affinity label of rat liver glutathione S-transferase, isozyme 1-1. A time
      dependent loss of enzyme activity is observed upon incubation of 3beta-IDA with
      the enzyme. The rate of enzyme inactivation exhibits a nonlinear dependence on
      3beta-IDA concentration, yielding an apparent Ki of 21 microM. Upon complete
      inactivation of the enzyme, a reagent incorporation of approximately 1 mol/mol of
      enzyme subunit or 2 mol/mol of enzyme dimer is observed. Protection against
      inactivation and incorporation is afforded by alkyl glutathione derivatives and
      nonsubstrate steroid ligands such as 17beta-estradiol-3,17-disulfate but,
      surprisingly, not by Delta5-androstene-3,17-dione or any other electrophilic
      substrate analogues tested. These results suggest that the site of reaction is
      within the nonsubstrate steroid binding site of the enzyme, which is
      distinguishable from the electrophilic substrate binding site, near the active
      site of the enzyme. Two cysteine residues, Cys17 and Cys111, are modified in
      nearly equal amounts, despite an average reagent incorporation of 1 mol/mol
      enzyme subunit. Isolation of enzyme subunits indicates the presence of
      unmodified, singly labeled, and doubly labeled subunits, consistent with mutually
      exclusive modification of cysteine residues across enzyme subunits; i.e.,
      modification of Cys111 on subunit A prevents modification of Cys111 on subunit B
      and similarly for Cys17. Molecular modeling analysis suggests that Cys17 and
      Cys111 are located in the nonsubstrate steroid binding site, within the cleft
      between the subunits of the dimeric enzyme.

PMID- 9281308
TI  - Mechanism of differential catalytic efficiency of two polymorphic forms of human
      glutathione S-transferase P1-1 in the glutathione conjugation of carcinogenic
      diol epoxide of chrysene.
AB  - The kinetics of the conjugation of glutathione (GSH) with anti-1, 2-dihydroxy-3,4
      oxy-1,2,3,4-tetrahydrochrysene (anti-CDE), the activated form of the widespread
      environmental pollutant chrysene, catalyzed by two naturally occurring
      polymorphic forms of the pi class human GSH S-transferase (hGSTP1-1), has been
      investigated. The polymorphic forms of hGSTP1-1, which differ in their primary
      structure by a single amino acid in position 104, exhibited preference for the
      GSH conjugation of (+)-anti-CDE, which is a far more potent carcinogen than (-)
      anti-CDE. When concentration of anti-CDE was varied (5-200 microM and the GSH
      concentration was kept constant at 2 mM, both hGSTP1-1(I104) and hGSTP1-1(V104)
      obeyed Michaelis-Menten kinetics. However, the Vmax of GSH conjugation of anti
      CDE was approximately 5.3-fold higher for the V104 variant than for the I104
      form. Calculation of catalytic efficiency (kcat/Km) thus resulted in a value for
      hGSTP1-1(V104), 28 mM-1 s-1, that was 7.0-fold higher than that for hGSTP1
      1(I104), 4 mM-1 s-1. The mechanism of the differences in the kinetic properties
      of hGSTP1-1 isoforms toward anti-CDE was investigated by molecular modeling of
      the two proteins with GSH conjugation products in their active sites. These
      studies revealed that the enantioselectivity of hGSTP1-1 for (+)-anti-CDE and the
      differential catalytic efficiencies of the V104 and I104 forms of hGSTP1-1 in the
      GSH conjugation of (+)-anti-CDE were due to the differences in the active-site
      architecture of the two proteins. The results of the present study, for the first
      time, provide evidence for the toxicological relevance of GSTP1-1 polymorphism in
      humans and suggest that the population polymorphism of hGSTP1-1 variants with
      disparate enzyme activities may, at least in part, account for the differential
      susceptibility of individuals to environmental carcinogens such as anti-CDE and
      possibly other similar carcinogens.

PMID- 9281309
TI  - Oxidative interaction of unpaired hemoglobin chains with lipids and proteins: a
      key for modified serum lipoproteins in thalassemia.
AB  - We searched for a biochemical explanation to the modification of lipoproteins
      like low-density lipoproteins (LDL) observed in patients with the severe
      hemolytic anemia beta-thalassemia. Because a large fraction of the LDL surface is
      composed of phospholipids, we first explored the possible involvement of
      phospholipids in the oxidative interaction of LDL with hemoglobin (Hb), using
      brain extract phospholipid liposomes as a model. The relative binding affinity
      and oxidative interaction of three hemoglobin variants (intact Hb A and isolated
      beta- and alpha-chains) with LDL and liposome were compared. Studies carried out
      at low pH/ionic strength and under physiological conditions revealed that
      association of hemoglobin variants with the phospholipid liposomes is driven by
      electrostatic forces but their binding is not a prerequisite for oxidative
      interaction. Unlike phospholipid liposomes, LDL underwent only a negligible
      association with the Hb variants under all pH/ionic strength conditions.
      Nevertheless, LDL induced oxidation of Hb variants, mostly alpha-chains. The
      dissimilar behavior of the liposomes and LDL indicated that LDL protein apo B
      rather than phospholipids is the actual LDL surface component which interacts
      with the hemoglobin variants. This agrees with the finding that apo B protein
      underwent oxidative crosslinking by the hemoglobin variants among which alpha
      chains were most active. We concluded from these results that the ability of
      hemoglobin to undergo autooxidation is the key to its oxidative reactivity toward
      LDL. The results of the present study indicate that the modified LDL particles
      observed in beta-thalassemia may reflect lipoprotein oxidation by alpha-chains in
      circulation.

PMID- 9281310
TI  - Pancreatic exocrine secretion is blocked by inhibitors of methylation.
AB  - A number of early experiments suggested a relationship between methyl group
      metabolism and the exocrine secretion of the pancreas. These included nutritional
      studies showing that ethionine, the ethyl analog of methionine which inhibits
      cellular methylation reactions, is a specific pancreatic toxin. Other studies
      indicated that protein carboxymethylation might be involved. We now show that in
      vivo ethionine inhibits amylase secretion from freshly isolated rat pancreatic
      acini, while in vitro ethionine inhibits amylase secretion from the AR42J
      pancreatic cell line. S-Adenosylhomocysteine (SAH) is a product inhibitor of all
      methyltransferase reactions involving S-adenosylmethionine (SAM), and treatments
      that elevate cellular levels of SAH such as inhibition of S-adenosylhomocysteine
      hydrolase and the in vitro addition of adenosine and homocysteine result in the
      inhibition of amylase secretion in both isolated pancreatic acini and AR42J
      cells. Measurement of SAM and SAH levels in AR42J cells shows that inhibition of
      secretion is more closely related to elevation of SAH levels than to a decrease
      in the SAM/SAH ratio. Small G-proteins are carboxymethylated on the C-terminal
      prenylated cysteine and inhibitors of membrane-associated prenylcysteine
      methyltransferase, N-acetylfarnesylcysteine, N-acetylgeranylgeranylcysteine, and
      farnesylthioacetic acid (FTA), block secretion in AR42J cells. N
      Acetylgeranylcysteine is not an inhibitor of the methyltransferase and does not
      inhibit amylase secretion. FTA inhibits membrane-associated prenylcysteine
      methyltransferase from AR42J cells with a Ki in the 45-69 microm range. These
      results suggest that a methylation event is needed for pancreatic exocrine
      secretion which may be the reversible methylation of a G-protein involved in
      signal transduction or membrane trafficking.

PMID- 9281312
TI  - Genistein sensitivity of calcium transport pathways in serotonin-activated
      vascular smooth muscle cells.
AB  - Recent studies showed that serotonin-activated increases in intracellular Ca2+ in
      vascular smooth muscle cells are associated with enhanced protein tyrosine
      phosphorylation. These responses were blocked by inhibition of tyrosine kinase
      activity with genistein, suggesting that the increases in Ca2+ and tyrosine
      phosphorylation are functionally coupled. Therefore, we sought to characterize
      genistein-sensitive Ca2+ transport pathways in rat aortic A10 cells loaded with
      fura-2. In the presence of extracellular Ca2+, serotonin evoked a transient
      increase in [Ca2+]i that was followed by a smaller sustained increase. The
      transient was inhibited 25-40% by L-type Ca2+ channel antagonists and inhibited
      90-95% by genistein. The sustained response was unaffected by L-channel
      antagonists and only slightly inhibited by genistein. In the absence of
      extracellular Ca2+, the transient was reduced by 50%, while the sustained
      component was virtually abolished. These results suggest that influx and release
      pathways are major contributors to the transient component, whereas the lower
      sustained component is largely limited to influx pathways. The influx pathway
      during the transient probably involves an L-type Ca2+ channel that is regulated
      by tyrosine kinase activity. The pathways that participate in the sustained
      response are different because they are insensitive to l-channel antagonists and
      only slightly inhibited by genistein. The transient evoked in Ca2+-free media was
      blocked by genistein, inhibited by caffeine, and prevented by thapsigargin.
      Ionomycin-induced release of Ca2+ was unaffected by genistein, reduced by
      caffeine, and essentially eliminated by thapsigargin. Therefore, thapsigargin
      mediated suppression of serotonin-activated release probably reflects depletion
      of Ca2+ from the sarcoplasmic reticulum, whereas genistein-mediated suppression
      probably reflects inhibition of tyrosine kinase linked release. Caffeine-mediated
      suppression appears to involve both partial depletion of Ca2+ and interference
      with release. Each A10 cell expressed at least two different ryanodine receptors
      and two different receptors for inositol 1,4,5-trisphosphate.

PMID- 9281311
TI  - Purification and characterization of a cytochrome P450 from liver microsomes of
      Xenopus laevis.
AB  - A new cytochrome P450 (P450) has been purified to near homogeneity from Xenopus
      laevis liver microsomes. Two steps of column chromatographies (n-octylamino
      Sepharose 4B and Mono Q) and fast protein liquid chromatofocusing were performed
      consecutively, and the final preparation containing 19 nmol P450/mg protein gave
      a single band of 52 kDa on SDS-PAGE at an isoelectric point of 6.7. This enzyme
      had a common feature of microsomal P450s in NH2-terminal region, and some of the
      internal sequences were similar to the corresponding sequences of reported P450s.
      The purified Xenopus P450 cross-reacted with antibodies against CYP2B1, rat
      CYP2E1, and CYP2C13, but not with rat CYP1A1, CYP3A2, or CYP4A1. Upon
      reconstitution with rat NADPH-cytochrome P450 reductase and phospholipid, the
      Xenopus P450 catalyzed aniline hydroxylation and N-nitrosodimethylamine N
      demethylation. Cytochrome b5 enhanced these reactions. This P450 did not catalyze
      the hydroxylation of either hexobarbital or testosterone. Thus, the catalytic
      activities of this P450 were comparable with those of mammalian CYP2E1.
      Expression of this P450 was observed in liver, kidney, lung, and testis, and the
      level was highest in kidney. Tissue specificity of expression was the same in
      both male and female frogs.

PMID- 9281313
TI  - Purification, characterization, and hydrodynamic properties of arginine kinase
      from gulf shrimp (Penaeus aztecus).
AB  - Arginine kinase from the tail muscle of the Gulf shrimp (Penaeus aztecus) was
      purified to apparent homogeneity, using a rapid, high-yield method. The protein
      exhibits a molecular weight of 40 kDa according to the methods of gel filtration
      and gel electrophoresis in sodium dodecyl sulfate, also indicating that arginine
      kinase from shrimp is a monomer. The amino acid content of arginine kinase from
      shrimp is similar to arginine kinases from several species and to creatine kinase
      from rabbit muscle. Arginine kinase derivatized at the reactive sulfhydryl with 2
      (4'-(iodoacetamido)anilino)naphthalene-6-sulfonic acid exhibits significant
      changes in fluorescence anisotropy only in the presence of the guanidino
      substrate and the so-called "dead-end complex" containing arginine + MgADP.
      Several compounds structurally similar to arginine, e.g., ornithine do not
      interact with arginine kinase, suggesting a narrow specificity for substrate
      binding. The most suitable description of the decay of the fluorescence of
      arginine kinase derivatized with 5-[(((acetyl)-amino)ethyl)amino]naphthalene-1
      sulfonate (AEDANS-AK), from among discrete and distributed models, is a triple
      exponential discrete decay. The presence of the dead-end complex only marginally
      increases the rate of decay, but significantly shifts the magnitude of the
      preexponentials (amplitudes) between the two major decay components. One
      interpretation of these results is that multiple conformational isomers may
      occur, in which the relative concentrations are dependent upon the presence of
      the dead-end complex. Measurement of the time-dependent anisotropy decay of
      AEDANS-AK reveals a two-term decay law with rotational correlation times of 0.88
      and 15.2 ns. The slower component is close to the theoretical value of 16.7 ns
      for an isotropic rotator of the molecular mass of arginine kinase. This finding
      suggests that the overall conformation of arginine kinase may differ considerably
      from the prolate ellipsoidal subunits of the functionally analogous creatine
      kinase.

PMID- 9281314
TI  - Active site analysis of P450 enzymes: comparative magnetic circular dichroism
      spectroscopy.
AB  - Recent structural studies indicate that the substrate- and O2-binding distal
      pocket of the P450 enzymes are not identical. Thus, P450terp (CYP108) from the
      alpha-terpineol-metabolizing Pseudomonad differs from P450cam (CYP-101) (C. A.
      Hasemann et al., J. Mol. Biol. 236, 1169, 1994). In contrast, the distal pockets
      of P450terp and P450BMP (CYP102 heme domain; Bacillus megaterium) are more
      closely similar, including novel hydrogen-bonding interactions between the distal
      H2O ligand and the I helix (C. A. Hasemann et al., Structure, 3, 41-62, 1995). To
      evaluate the significance of these differences, we have compared solution
      magnetic circular dichroism (MCD) spectra of P450terp with spectra of other P450
      enzymes (e.g., P450cam, P450BMP, P450BM-3holo, and P450BM1), as well as with
      spectra of chloroperoxidase and NO synthase. Spectra of native P450terp are more
      similar to those of P450BMP and those of mammalian P450LM-2 than to those of
      P450cam. Upon substrate-binding, the MCD spectra of ferric P450terp and all other
      thiolate-ligated heme systems examined to date display a strong Soret band that
      is distinctly unique relative to the typical Soret MCD pattern(s) of catalases or
      other 5-coordinate ferric heme systems. This intense negative MCD feature thus
      appears diagnostic for cysteinate-linked ferric hemes. In the case of ferrous
      P450s, the intensity of the Soret-region MCD trough varies between substrate
      bound and substrate-free enzymes (despite the fact that the substrate is NOT in
      direct contact with the heme moiety). A novel finding of particular interest is
      the clear spectral shifts of the Soret MCD band between the substrate-bound and
      substrate-free forms of ferrous-CO-P450terp. No such observation has been made
      previously. Furthermore, the band positions for BOTH types of P450terp are red
      shifted from known bands of ferrous-CO-P50cam. These data thus indicate a
      surprising sensitivity of MCD spectra to active-site polarity and to H2O
      occupancy, concurring with reports of distal pocket effects on CO-binding rates
      and equilibrium constants. Comparative analysis of the spectral properties of
      P450terp with MCD spectra of other P450 enzymes, as well as with chloroperoxidase
      and NO synthase, demonstrates both the expected similarities and the significant
      differences that reflect active-site structural features. The detailed spectral
      analysis of P450terp relative to other P450 enzymes presented herein includes the
      first observation of a substrate-induced spectral shift for a ferrous-CO-P450.
      Furthermore, testable structural predictions for P450-BM-1 and for the novel NO
      synthase enzyme (neither of which has been crystallized to date) are made herein.
      This work thus provides insights into structurally defined P450s and may also
      lead to understanding of other P450 enzymes.

PMID- 9281315
TI  - Direct electrochemistry of the flavin domain of assimilatory nitrate reductase:
      effects of NAD+ and NAD+ analogs.
AB  - Direct electrochemical studies, utilizing two voltammetric methods-square-wave
      voltammetry (SWV) and cyclic voltammetry (CV)-have been performed on recombinant
      forms of the flavin domain of spinach assimilatory nitrate reductase in the
      presence of NAD+ analogs. The reduction potentials (E degrees ') of the flavin
      domains have been determined at an edge pyrolytic graphite electrode utilizing
      MgCl2 as a redox-inactive promoter. Under identical experimental conditions (pH
      7.0, 25 degrees C), the two-electron reduction potential for the FAD/FADH2 couple
      has been determined to be -274 and -257 mV by SWV and CV, respectively. In
      contrast, the reduction potentials of free FAD have been determined to be -234
      and -227 mV by SWV and CV, respectively. The reduction potentials of the complex
      formed between the FAD prosthetic group in the recombinant flavin domain and
      various NAD+ analogs have been determined to be as follows: NAD+ (E degrees ' = 
      192 mV), 5'-ADP ribose (E degrees ' = -199 mV), ADP (E degrees ' = -154 mV), AMP
      (E degrees ' = -196 mV), adenosine (E degrees ' = -192 mV), adenine (E degrees '
      = -220 mV), and NMN (E degrees ' = -208 mV). In contrast to these positive shifts
      in reduction potential, nicotinamide (E degrees ' = -268 mV) had very little
      effect on the reduction potential of this flavin complex. Moreover, addition of
      NAD+ to the FAD prosthetic group in a variety of mutant forms of the recombinant
      flavin domain resulted in positive shifts in the reduction potential of the
      complex, although the magnitude of the shifts varied from a minimum of 6 mV
      obtained for the C240A mutant to a maximum of 79 mV obtained for the C62S mutant.
      These results represent the first extensive application of direct
      electrochemistry to examine the redox properties of assimilatory nitrate
      reductase and indicate that complex formation with NAD+, or various NAD+ analogs,
      results in a positive shift in the flavin reduction potential, with the magnitude
      of the shift correlating well with the efficiency of the inhibitor.

PMID- 9281316
TI  - Inhibition of methionine adenosyltransferase by the polyamines.
AB  - The effect of the polyamines, putrescine, spermine, and spermidine, on the
      activity of extrahepatic methionine adenosyltransferase (MAT II) was studied. The
      polyamines inhibited MAT II activity at concentrations equal to or greater than 5
      mm. Combinations of polyamines were more effective than individual polyamines in
      inhibiting MAT activity; maximum inhibition approached 80% with combinations of
      all three polyamines. S-Adenosylmethionine (AdoMet), Pi, and PPi, the products of
      the MAT reaction, are known to be synergistic inhibitors of the nonhepatic form
      of the enzyme. Combinations of polyamines plus Pi and/or PPi induced an additive
      inhibition of the enzyme. AdoMet plus polyamines also resulted in significant
      inhibition, but inhibition plateaued at about 80%, indicating the presence of a
      protective mechanism to maintain AdoMet synthesis. Extrahepatic MAT from human
      and rat tissues was inhibited by the polyamines, indicating that this phenomenon
      is not species specific. In addition, we examined the effect of polyamines on MAT
      activity in resting and activated human lymphocytes that were shown to differ in
      the relative expression of MAT II subunits. Although MAT from mitogen
      (phytohemagglutinin, PHA)- and superantigen (Staphylococcal enterotoxin B, SEB)
      stimulated lymphocytes were similarly inhibited by 10 mM polyamines, at lower
      concentrations of polyamines (1-5 mM), MAT from SEB-stimulated cells appeared to
      be more susceptible to inhibition by the polyamines. Inasmuch as SEB is a more
      physiological stimulator of T cells than PHA, the data suggest a possible role of
      polyamines in regulating MAT activity.

PMID- 9281317
TI  - A new function for phospholipase C-gamma1: coupling to the adaptor protein GRB2.
AB  - Epidermal growth factor (EGF)-induced autophosphorylation of the EGF receptor
      results in high-affinity binding of the adaptor protein GRB2, which serves as a
      convergence point for multiple signaling pathways. Present studies demonstrate
      that EGF induces the co-immunoprecipitation of phospholipase C (PLC)-gamma1 with
      the adaptor protein GRB2 and the guanine nucleotide exchange factor Sos, but not
      with the adaptor protein SHC, in WB cells. Inhibition of PLC-gamma1 tyrosine
      phosphorylation by phenylarsine oxide reduces the co-immunoprecipitation of PLC
      gamma1 with GRB2. Furthermore, angiotensin II, a G protein-coupled receptor
      agonist, also induces the tyrosine phosphorylation of PLC-gamma1 and its co
      immunoprecipitation with GRB2 in WB cells. Interestingly, angiotensin II
      stimulation also causes tyrosine phosphorylation of the EGF receptor, suggesting
      that angiotensin II-induced PLC-gamma1 tyrosine phosphorylation in WB cells may
      be via EGF receptor tyrosine kinase activation. In addition, there is some level
      of association between PLC-gamma1 and GRB2 that is independent of the tyrosine
      phosphorylation of PLC-gamma1 in both in vivo and in vitro studies. In vitro
      studies further demonstrate that the Tyr771 and Tyr783 region of PLC-gamma1 and
      the SH2 domain of GRB2 are potentially involved in the tyrosine phosphorylation
      dependent association between PLC-gamma1 and GRB2. The association of PLC-gamma1
      with GRB2 and Sos suggests that PLC-gamma1 may be directly involved in the Ras
      signaling pathway and that GRB2 may be involved in the translocation of PLC
      gamma1 from cytosol to the plasma membrane as a necessary step for its effect on
      inositol lipid hydrolysis.

PMID- 9281319
TI  - Haloperoxidase activity of manganese peroxidase from Phanerochaete chrysosporium.
AB  - Manganese peroxidase (MnP) from Phanerochaete chrysosporium exhibits
      haloperoxidase activity at low pH. In the presence of hydrogen peroxide, MnP
      oxidizes bromide and iodide as measured by the formation of tribromide and
      triiodide complexes and the halogenation of various organic substrates. The
      optimum pHs for bromide and iodide oxidation are 2.5 and 3.0, respectively.
      Transient-state kinetic studies show that the reaction between MnP compound I and
      bromide or iodide occurs via a single two-electron step process, obeying second
      order kinetics. The second-order rate constants for MnP compound I reduction by
      bromide and iodide are (4.1 +/- 0.2) x 10(3) and (1.1 +/- 0.1) x 10(5) m-1 s-1,
      respectively, at pH 3.0. MnP brominates a variety of aromatic substrates,
      including veratryl (3,4-di-methoxybenzyl) alcohol (I) to produce of 2-bromo-4,5
      dimethoxybenzyl alcohol (II). MnP also hydrobrominates cinnamic acid (VI) to
      produce 2-bromo-3-hydroxyphenylpropionic acid (VII). With 3,4-dimethoxycinnamic
      acid (III) as the substrate, two bromination products are identified: trans-2
      bromo-1-(3, 4-dimethoxyphenyl) ethylene (IV) and 2-bromo-3-(3, 4-dimethoxyphenyl)
      3-hydroxypropionic acid (V). MnP also brominates 1,3-dicarbonyl compounds such as
      monochlorodimedone and malonic acid. Incubation of MnP with bromide and H2O2 in
      the absence of organic substrates results in enzyme inactivation. MnP binds
      halides to produce characteristic optical difference spectra. From these spectra,
      apparent dissociation constants at pH 3.0 are determined to be 0.13, 20, and 45
      mm for fluoride, chloride, and bromide, respectively.

PMID- 9281318
TI  - Structural determinants for the intracellular localization of the isozymes of
      mammalian hexokinase: intracellular localization of fusion constructs
      incorporating structural elements from the hexokinase isozymes and the green
      fluorescent protein.
AB  - Fusion constructs incorporating structural elements from mammalian isozymes of
      hexokinase, Types I-IV, in frame with sequence encoding the green fluorescent
      protein (GFP) have been made and expressed in hexokinase-deficient M + R 42
      cells. Fusion proteins incorporating catalytically active regions from the Type
      II isozyme, or the entire Type IV sequence, were expressed in catalytically
      active form. The intracellular localization of the fusion proteins was determined
      using confocal microscopy. Fusion proteins including the N-terminal halves of the
      Type I or Type II isozymes were targeted to mitochondria, while the N-terminal
      half of the Type III isozyme did not confer mitochondrial targeting. The
      mitochondrial targeting signal was represented by the hydrophobic sequence at the
      extreme N-termini ("binding domain") of the Type I and Type II isozymes.
      Inclusion of the binding domain from the Type I isozyme was sufficient to confer
      mitochondrial binding on GFP itself as well as on constructs including the N
      terminal half of Type III hexokinase. However, the Type I hexokinase binding
      domain was not sufficient to cause mitochondrial targeting of a construct
      containing the Type IV sequence. These results suggest that, although the binding
      domain is critical for mitochondrial targeting, other interactions involving an
      adjacent structure might also play a role. Fusion proteins including the N
      terminal half of Type I hexokinase became dissociated from mitochondria under
      conditions favorable for accumulation of intracellular Glc-6-P. The 2-deoxy
      analog was much less effective than Glc in causing mitochondrial dissociation of
      the fusion construct, in accord with previous studies showing 2-deoxy-Glc-6-P to
      be much less effective than Glc-6-P at promoting release of Type I hexokinase
      from mitochondria. Dissociation, induced by formation of Glc-6-P or 2-deoxy-Glc-6
      P, did not occur with the fusion protein including only the binding domain of
      Type I hexokinase. This is consistent with previous studies indicating that Glc-6
      P-dependent dissociation results from binding of this ligand to a site in the N
      terminal half of the enzyme, but which is not likely to be present in the small
      segment represented by the binding domain. These studies demonstrate the
      usefulness of this approach in defining structural elements involved in targeting
      hexokinase isozymes to specific subcellular locations and modulation of that
      intracellular location by perturbations of metabolic status.

PMID- 9281320
TI  - Expression, purification, and initial characterization of human Yes protein
      tyrosine kinase from a bacterial expression system.
AB  - Protein tyrosine kinase Yes is a cellular homolog of v-Yes, the oncogenic protein
      product of avian sarcoma virus Y73. Yes is a member of the Src family and its
      activation has been associated with several types of human cancer. Human Yes has
      not been previously characterized enzymatically. To carry out biochemical
      characterizations of this enzyme, we expressed it as a fusion protein with
      glutathione S-transferase in Escherichia coli, to allow purification in a single
      step. The affinity-purified GST-Yes has a specific activity of 1.3 nmol min-1 mg
      1 with polyE4Y as substrate and Km values of 100 microg ml-1 for polyE4Y and 70
      microM for ATP-Mg. The enzyme has a preference for magnesium over manganese ion
      for maximal activity. The divalent metal cation serves two essential functions
      for the activity of Yes: one as a part of the phosphate-donating substrate ATP-Mg
      and the other as an essential activator. The enzyme undergoes autophosphorylation
      without apparent activation. Finally, we show that the enzyme is inactivated by
      incubation with protein tyrosine kinase Csk in an ATP-Mg-dependent manner,
      indicating that cellular Yes can be regulated by Csk phosphorylation. These
      represent the first biochemical characterization of human Yes protein tyrosine
      kinase.

PMID- 9281321
TI  - Enzymatic properties of human Na,K-ATPase alpha1beta3 isozyme.
AB  - Recent results of a wide-scale human cDNA sequencing project have identified a
      cDNA which encodes a hitherto unknown human protein sequence exhibiting
      structural similarities with beta-subunits of the Na,K- and H,K-ATPase family and
      with the amphibian Na,KATPase beta3-subunit, in particular. In this study the
      ability of the putative human beta3-subunit to assemble with the human alpha1
      subunit in functionally active Na,KATPase was examined using the baculovirus
      expression system. The recombinant baculovirus simultaneously expressing both
      alpha1 and beta3 human proteins was produced using the dual-promoter transfer
      vector p2Bac. The expression of both human proteins in baculovirus-infected Sf-9
      cell membranes detected with specific antibodies resulted in the formation of a
      catalytically competent alpha1beta3 ATPase complex. Characterization of the
      recombinant ATPase complex involved the analysis of Na+, K+, and ATP dependencies
      of enzyme activity and its sensitivity toward ouabain. Preparations of HeLa cell
      membranes containing alpha1beta1 isozyme of human Na,K-ATPase were used as
      control. The data obtained clearly demonstrated that alpha1beta3 ATPase exhibits
      enzymatic properties which are characteristic of Na, K-ATPase. The recombinant
      alpha1beta3 isozyme displayed significantly lower sensitivity to ouabain than
      native alpha1beta1. These findings indicate that the hitherto unknown alpha1beta3
      isozyme of human Na,K-ATPase is likely to exist in vivo, thus suggesting further
      expansion of human Na,K-ATPase isozyme diversity. The present studies are the
      first in which heterologous expression has been used for the characterization of
      an isozyme of human Na, K-ATPase.

PMID- 9281322
TI  - Isolation from fetal bovine serum of a fragment b of complement factor B-like
      protein improving a long-term survival of human endothelial cells.
AB  - It is known that serum is a most important factor supporting cell survival and
      growth. Particularly, the deprivation of serum would result in the death of human
      endothelial cell. Our previous paper reported an endothelial cell-viability
      maintaining factor (EC-VMFa) purified from fetal bovine serum and identified as
      an apolipoprotein. In the present further study, it is demonstrated that another
      potent serum factor (refer as EC-VMFb) is also possessed of the endothelial cell
      viability maintaining activity, improving a long-term survival of human
      endothelial cells in serum-free medium. EC-VMFb has a molecular weight of 66,000
      (reduced and nonreduced), pI of 4.5 and has been identified as fragment b of
      complement factor B (Bb)-like protein by amino-terminal amino acid sequence.

PMID- 9281323
TI  - Effect of Val 73 --> Trp mutation on the reaction of "cambialistic" superoxide
      dismutase from Propionibacterium shermanii with hydrogen peroxide.
AB  - The H2O2 inactivation of the "cambialistic" superoxide dismutases from
      Propionibacterium shermanii, which is active with either iron or manganese at the
      active site, has been studied in the native and Val 73 --> Trp mutant enzymes.
      The wild-type iron-containing form of this enzyme is much more resistant to
      treatment with H2O2 with respect to the other metal-specific Fe superoxide
      dismutase isoenzymes. After incubation with high amounts of H2O2 the enzyme
      maintains more than 40% of the initial activity. The activity of the Val 73 -->
      Trp mutant drastically decreases to less than 5% of the initial activity after
      incubation with hydrogen peroxide. Amino acid analysis of the H2O2-treated mutant
      enzyme evidenced the loss of the Trp 73 residue which is shown to play a critical
      role in the stabilization of the monomer fold of the enzyme. On the other hand,
      the manganese-containing wild-type and mutant enzymes were completely resistant
      toward H2O2 demonstrating the specific role of iron in the inactivation process.

PMID- 9281324
TI  - Carbon dioxide modulation of hydroxylation and nitration of phenol by
      peroxynitrite.
AB  - We have examined the formation of hydroxyphenols, nitrophenols, and the minor
      products 4-nitrosophenol, benzoquinone, 2,2'-biphenol, and 4,4'-biphenol from the
      reaction of peroxynitrite with phenol in the presence and absence of added
      carbonate. In the absence of added carbonate, the product yields of nitrophenols
      and hydroxyphenols have different pH profiles. The rates of nitration and
      hydroxylation also have different pH profiles and match the trends observed for
      the product yields. At a given pH, the sum of the rate constants for nitration
      and hydroxylation is nearly identical to the rate constant for the spontaneous
      decomposition of peroxynitrite. The reaction of peroxynitrite with phenol is zero
      order in phenol, both in the presence and absence of added carbonate. In the
      presence of added carbonate, hydroxylation is inhibited, whereas the rate of
      formation and yield of nitrophenols increase. The combined maximum yield of o-
      and p-nitrophenols is 20 mol% (based on the initial concentration of
      peroxynitrite) and is about fourfold higher than the maximal yield obtained in
      the absence of added carbonate. The o/p ratio of nitrophenols is the same in the
      presence and absence of added carbonate. These results demonstrate that
      hydroxylation and nitration occur via two different intermediates. We suggest
      that the activated intermediate formed in the isomerization of peroxynitrous acid
      to nitrate, ONOOH*, is the hydroxylating species. We propose that intermediate 1,
      O=N-OO-CO2-, or secondary products derived from it, is (are) responsible for the
      nitration of phenol. The possible mechanisms responsible for nitration are
      discussed.

PMID- 9281325
TI  - Betaine-homocysteine methyltransferase expression in porcine and human tissues
      and chromosomal localization of the human gene.
AB  - We have prepared antibodies against porcine liver betaine-homocysteine
      methyltransferase (BHMT; EC 2.1.1.5) and recently cloned cDNAs encoding the
      porcine and human liver enzymes. Porcine tissues were evaluated for BHMT
      expression by measuring catalytic activity and Western analysis. Liver and kidney
      were the only organs tested that had immunodetectable levels of BHMT, and these
      organs expressed high levels of enzyme activity. BHMT was expressed in the kidney
      cortex and not the medulla. Porcine pancreas, brain, heart, lung, and spleen were
      devoid of BHMT activity and immunodetectable protein. Human tissues were tested
      for BHMT expression by Northern analysis. Human liver and kidney were the only
      organs tested that expressed BHMT mRNA. Human pancreas, brain, heart, skeletal
      muscle, spleen, and placenta were devoid of BHMT mRNA. The human BHMT gene has
      been mapped to chromosome 5q13.1-q15.

PMID- 9281326
TI  - Visualization-based analysis of multiparameter models using environment for N
      dimensional model analysis.
AB  - We present a methodology, based on N-dimensional computer visualization, for
      analyzing multiparameter models. This approach originally consisted of three
      steps: behavior analysis, sensitivity analysis, identifiability analysis. We have
      now developed a new way of calculating sensitivity based on the statistical
      measure of the coefficient of variation. Furthermore, we extended the methodology
      through the addition of an extra step, visual regression. Visual regression
      allows the user to visualize the process of actual parameter identification and
      presents a combined, empirical view of the first three steps in a single image.
      Next we applied this methodology to pulmonary capillary-transport models.
      Finally, we implemented the model analysis process as a stand-alone program. EN
      DIMAN, the resulting software, allows researchers to carry out model analysis in
      a graphical user interface (GUI)-based environment.

PMID- 9281327
TI  - Detecting chaos in HRV signals in human cardiac transplant recipients.
AB  - A statistical approach to chaos identification in time series is presented. The
      method is applied to numerical data generated by chaotic systems and to heart
      rate variability (HRV) signals of normal subjects and heart transplant
      recipients. This method compares the short-term predictability for a given time
      series to an ensemble of random data which has the same Fourier spectrum as the
      original time series. The short-term prediction error is computed as a
      discriminating statistic for performing statistical hypothesis testing. The
      results suggest that HRV signals of the transplant recipients recorded 3 months
      after the transplantations show the same signature of chaos as that of the HRV
      signals for normal subjects.

PMID- 9281328
TI  - Evaluation of QRS morphological classifiers in the presence of noise.
AB  - This paper analyzes the performance of four similarity measures (distances: d1,
      d2, and dinfinity, as well as correlation coefficient), when they are employed
      for morphological classification of QRS complexes by means of linear cluster
      formation. An important characteristic that any morphological classification
      method for QRS complexes should possess is the ability to perform waveform
      recognition despite the wide variety in which these could appear, as well as the
      diverse types of noise that could contaminate the signal. Evaluation of these
      classifiers constitutes an important problem for their selection. Evaluation was
      performed using electrocardiographic signals selected from the MIT-BIH database.
      These signals were contaminated with several noise types that are found in the
      environment where electrocardiograms are usually registered and processed, and
      the different noise waveforms were combined in an appropriate way to simulate
      practical situations, including some with severe noise contamination. Results are
      expressed in terms of probabilities of correct classification for different
      signal to noise ratios, allowing a comparison between the different distance
      measures in terms of their effectiveness.

PMID- 9281330
TI  - Use of computer interview data to test associations between risk factors and
      pregnancy outcomes.
AB  - Computer interviews have been used in a variety of settings as a means of
      gathering data and providing health education information. The objective of this
      study was to determine whether data gathered from a computer interview have
      predictive validity in determining pregnancy outcomes. Pregnant women (N = 190)
      completed a computer-assisted interview to provide risk factor information.
      Medical records were reviewed to obtain prenatal and birth outcome information.
      Twenty-nine percent experienced prenatal complications and nearly half
      experienced problems related to labor and delivery. After known risk factors were
      controlled for, self-reported psychosocial problems, low social support, and
      substance abuse by the father were associated with pregnancy complications. An
      unbalanced diet and low social support were associated with lower infant birth
      weight. Findings suggest that data collected via computer interviews can provide
      useful risk factor screening information.

PMID- 9281329
TI  - Combining tabular, rule-based, and procedural knowledge in computer-based
      guidelines for childhood immunization.
AB  - IMM/Serve is a computer program which implements the clinical guidelines for
      childhood immunization. IMM/Serve accepts as input a child's immunization
      history. It then indicates which vaccinations are due and which vaccinations
      should be scheduled next. The clinical guidelines for immunization are quite
      complex and are modified quite frequently. As a result, it is important that
      IMM/Serve's knowledge be represented in a format that facilitates the maintenance
      of that knowledge as the field evolves over time. To achieve this goal, IMM/Serve
      uses four representations for different parts of its knowledge base: (1)
      Immunization forecasting parameters that specify the minimum ages and wait
      intervals for each dose are stored in tabular form. (2) The clinical logic that
      determines which set of forecasting parameters applies for a particular patient
      in each vaccine series is represented using if-then rules. (3) The temporal logic
      that combines dates, ages, and intervals to calculate recommended dates, is
      expressed procedurally. (4) The screening logic that checks each previous dose
      for validity is performed using a decision table that combines minimum ages and
      wait intervals with a small amount of clinical logic. A knowledge maintenance
      tool, IMM/Def, has been developed to help maintain the rule-based logic. The
      paper describes the design of IMM/Serve and the rationale and role of the
      different forms of knowledge used.

PMID- 9281331
TI  - A system for analysis of arterial blood pressure waveforms in humans.
AB  - Recent developments in arterial hemodynamics have indicated that the human
      arterial pressure waveform contains more information than is available from
      conventional sphygmomanometry. This information includes indices describing left
      ventricular systolic function and arterial properties. A cheap and reliable
      system was designed and implemented using readily available hardware for
      recording, analysis, and storage of arterial pressure waveforms. The system
      embodies an online technique for synthesizing ascending aortic pressure waveform
      from recordings made at different peripheral sites of the human arterial system.
      Eighteen indices are then derived from arterial pressure waveforms. This system
      can be used in an outpatient clinic for assisting in current pharmacological
      management of cardiovascular disease. It can also be extended to the critical
      care area, where the extra information provided aid in assessing the patient's
      condition.

PMID- 9281332
TI  - Role of FGF and noggin in neural crest induction.
AB  - A study of the molecules noggin and fibroblast growth factor (FGF) and its
      receptor in the induction of the prospective neural crest in Xenopus laevis
      embryos has been carried out, using the expression of the gene Xslu as a marker
      for the neural crest. We show that when a truncated FGF receptor (XFD) was
      expressed ectopically in order to block FGF signaling Xslu expression was
      inhibited. The effect of XFD on Xslu was specific and could be reversed by the
      coinjection of the wild-type FGF receptor (FGFR). Inhibition of Xslu expression
      by XFD is not a consequence of neural plate inhibition, as was shown by analyzing
      Xsox-2 expression. When ectoderm expressing XFD was transplanted into the
      prospective neural fold region of embryos Xslu induction was inhibited. The
      neural crest can also be induced by an interaction between neural plate and
      epidermis. As this induction is suppressed by the presence of XFD in the neural
      plate and not in the epidermis, it suggests that the neural crest is induced by
      FGF from the epidermis. However, treatment of neural plate with FGF was not able
      to induce Xslug expression, showing that in addition to FGF other non-FGF factors
      are also required. Previously we have suggested that the ectopic ventral
      expression of Xslu produced by overexpression of noggin mRNA resulted from an
      interaction of noggin with a ventral signal. Overexpression of XFD inhibits this
      effect, suggesting that FGF could be one component involved in this ventral
      signaling. Overexpression of FGFR produced a remarkable increase in the
      expression of Xslu in the posterior neural folds and around the blastopore.
      Injections in different blastomeres of the embryo suggest that the target cells
      of this effect are the ventral cells. Finally, we proposed a model in which the
      induction of the neural crests at the border of the neural plate requires
      functional FGF signaling, which possibly interacts with a neural inducer such as
      noggin.

PMID- 9281333
TI  - Cell cycle length affects gene expression and pattern formation in limbs.
AB  - The relationship between growth and pattern specification during development
      remains elusive. Some molecules known to function as growth factors are also
      potent agents of pattern formation. This raises the possibility that growth
      factors could act in pattern formation via an effect on the cell cycle. We have
      tested the significance of the length of the cell cycle for gene expression and
      pattern formation in developing chick limb buds by locally slowing the cell
      cycle. When anterior cell cycles are lengthened by reversible inhibition of DNA
      replication or by other means, some genes characteristic of the posterior
      polarizing region are expressed, and digit duplication is observed. Conversely,
      when posterior cell cycles are slowed, expression of some posterior-specific
      genes is inhibited, but the pattern is normal. These results indicate that
      control of the length of the cell cycle could play a primary role in pattern
      formation by influencing the complement of genes expressed in a particular region
      of the embryo.

PMID- 9281334
TI  - Specific inhibition of hair follicle formation by epidermal growth factor in an
      organ culture of developing mouse skin.
AB  - Embryonic mouse skin undergoes a drastic morphological change from 13 to 16
      gestational days, i.e., formation of rudiments of hair follicles and
      stratification and cornification of interfollicular epidermis. To investigate
      underlying molecular mechanisms of the morphogenesis, we established an organ
      culture system that allows skin tissues isolated from 12.5- or 13.5-days
      postcoitus embryos to develop in a manner that is histologically and temporally
      similar to the process in vivo. Expression of differentiation markers of
      epidermal keratinocytes including cholesterol sulfotransferase and cytokeratin K1
      was induced in culture, as it occurs also in vivo. The morphogenic process was
      observed by time-lapse videomicrography. In this culture system, epidermal growth
      factor (EGF) and transforming growth factor alpha specifically and completely
      inhibited the hair follicle formation with marginal effects on interfollicular
      epidermis. The inhibitory action by EGF was reversible and stage specific, i.e.,
      at an early stage of the development of hair rudiments. Among known ligands to
      the EGF receptor, Schwannoma-derived growth factor and heparin-binding EGF were
      expressed in in vivo epidermis during the period of the initial formation of hair
      follicles. EGF receptor is expressed in epidermis throughout the developing
      period examined. Using an adenovirus vector, we demonstrated that the lacZ gene
      was transduced into the epidermal and dermal cell layers without appreciable
      toxicity. These results indicate that the present culture system provides a
      unique opportunity to investigate molecular mechanisms of skin morphogenesis
      including the role of EGF signaling under defined experimental conditions.

PMID- 9281336
TI  - Equalization of unequal first cleavage in the Tubifex egg by introduction of an
      additional centrosome: implications for the absence of cortical mechanisms for
      mitotic spindle asymmetry.
AB  - The first cleavage in the Tubifex egg is unequal and involves a monastral mitotic
      apparatus (MA), which remains at the egg's center from metaphase through
      telophase. The monastral form of the MA is thought to arise due to the
      involvement of a single maternal centrosome in the MA assembly (R. Ishii and T.
      Shimizu, Dev. Growth Differ. 37, 687-701, 1995). To investigate the mechanisms
      that generate asymmetry in this division, we have examined the cleavage patterns
      in eggs that are manipulated to inherit two centrosomes during the first mitosis.
      When eggs are prevented from extruding polar bodies, centrosomes located at both
      poles of the first meiotic spindle persist into the first mitosis without showing
      any sign of duplication and generate astral spindle poles. Eggs that inherit
      these centrosomes exhibit two types of MA configurations, viz., an amphiastral MA
      and twin monastral MAs. We found that eggs with amphiastral MAs undergo bipolar
      equal divisions, while those with twin MAs divide into three cells simultaneously
      (tripolar divisions). The amphiastral MAs are located at the egg's center and
      their astral poles are organized symmetrically, suggesting that Tubifex eggs are
      unable to generate asymmetry in the amphiastral MAs during the first mitosis.
      These results suggest that inheritance of a single centrosome during the first
      mitosis is critical for Tubifex eggs to undergo unequal cleavage. We propose that
      the cortical mechanisms for MA asymmetry are lacking in the Tubifex egg during
      the first mitosis.

PMID- 9281335
TI  - Growth-promoting interaction of IGF-II with the insulin receptor during mouse
      embryonic development.
AB  - Genetic analyses of dwarfing phenotypes resulting from targeted mutagenesis of
      the genes encoding the insulin-like growth factors (IGF-I and IGF-II) and their
      cognate type 1 IGF receptor (IGF1R) have demonstrated that this signaling system
      is a major determinant of mouse embryonic growth. Of the two IGF ligands, IGF-I
      interacts exclusively with IGF1R, whereas IGF-II recognizes an additional
      receptor (XR), because the growth retardation of embryos lacking both IGR1R and
      IGF-II (30% of normal birthweight) is more severe than that manifested in either
      class of single Igf1r or Igf2 null mutants (45 and 60% of normal, respectively).
      To determine whether XR is the insulin receptor (IR), we examined embryos
      nullizygous for both Igf1r and Insr. While the growth of embryos lacking solely
      IR is affected very mildly and only at the end of gestation, concomitant absence
      of IGF1R results in a severe growth-deficiency phenotype (30% of normal size at
      birth) that is first detected at Embryonic Day 13.5 and is also characterized by
      transient edema, curly tail, generalized organ hypoplasia, including the muscles,
      developmental delays in ossification, and thin epidermis. The Igf1r/Insr double
      nullizygotes are phenotypically indistinguishable from double mutants lacking
      IGF1R and IGF-II and from other double and triple mutants in which all of the IGF
      ligand/receptor interactions have been eliminated. Therefore, these results
      provide genetic evidence that the growth-promoting function of IGF-II during
      mouse embryogenesis is mediated in part by signaling through the insulin
      receptor.

PMID- 9281337
TI  - Left/right patterning signals and the independent regulation of different aspects
      of situs in the chick embryo.
AB  - Recently, a pathway of genes which are part of a cascade regulating the side on
      which the heart forms during chick development was characterized (M. Levin et
      al., 1995, Cell 82, 1-20). Here we extend these previous studies, showing that
      manipulation of at least one member of the cascade, Sonic hedgehog (Shh), can
      affect the situs of embryonic rotation and of the gut, in addition to the heart.
      Bilateral expression of Shh, which is normally found exclusively on the left,
      does not result in left isomerism (a bilaterally symmetrical embryo having two
      left sides) nor in a complete situs inversus phenotype. Instead, misexpression of
      Shh on the right side of the node, which in turn leads to bilateral nodal
      expression, produces a heterotaxia-like condition, where different aspects of
      laterality are determined independently. Heart situs has previously been shown to
      be altered by ectopic Shh and activin. However, the most downstream gene
      identified in the LR pathway, nodal, had not been functionally linked to heart
      laterality. We show that ectopic (right-sided) nodal expression is able to affect
      heart situs, suggesting that the randomization of heart laterality observed in
      Shh and activin misexpression experiments is a result of changes in nodal
      expression and that nodal is likely to regulate heart situs endogenously. The
      first defined asymmetric signal in the left-right patterning pathway is Shh,
      which is initially expressed throughout Hensen's node but becomes restricted to
      the left side at stage 4(+). It has been hypothesized that the restriction of Shh
      expression may be due to repression by an upstream activin-like factor. The
      involvement of such an activin-like factor on the right side of Hensen's node was
      suggested because ectopic activin protein is able to repress Shh on the left side
      of the node, as well as to induce ectopic expression of a normally right-sided
      marker, the activin receptor cAct-RIIa. Here we provide further evidence in favor
      of this model. We find that a member of this family, Activin betaB, is indeed
      expressed asymmetrically, only on the right side of Hensen's node, at the correct
      time for it to be the endogenous asymmetric activin signal. Furthermore, we show
      that application of follistatin-loaded beads eliminates the asymmetry in Shh
      expression, consistent with an inhibition of an endogenous member of the activin
      BMP superfamily. This combined with the previous data on exogenous activin
      supports the model that Activin betaB functions in the chick embryo to initiate
      Shh asymmetry. While these data extend our understanding of the early signals
      which establish left-right asymmetry, they leave unanswered the interesting
      question of how the bilateral symmetry of the embryo is initially broken to
      define a consistent left-right axis. Analysis of spontaneous chick twins suggests
      that, whatever the molecular mechanism, left-right patterning is unlikely to be
      due to a blastodermal prepattern but rather is initiated in a streak-autonomous
      manner.

PMID- 9281338
TI  - Organizer induction determines left-right asymmetry in Xenopus.
AB  - Vertebrates appear bilaterally symmetrical but have considerable left-right (LR)
      asymmetry in the anatomy and placement of internal organs such as the heart.
      Although a number of asymmetrically expressed genes are known to affect LR
      patterning, both the initial source of asymmetry and the mechanism that correctly
      orients the LR axis remain controversial. In this study, we show that the
      induction of dorsal organizing centers in the embryo can orient LR asymmetry.
      Ectopic organizing centers were induced by microinjection of mRNA encoding a
      variety of body axis duplicating proteins, including members of the Wnt signal
      transduction pathway. The ectopic and primary body axes form side-by-side
      conjoined twins, with the secondary axis developing as either the left or right
      sibling. In all cases, correct LR asymmetry was observed in the left twin,
      regardless of whether it was derived from the primary axis or induced de novo by
      injection of Xwnt-8, beta-catenin, or Siamois mRNA. In contrast, the right twin
      was generally unbiased, regardless of the origin of the left body axis, as seen
      in many instances of experimentally induced and spontaneous conjoined twins. An
      unanticipated exception was that right twins induced by beta-catenin and Siamois,
      two downstream effectors of Wnt signaling, exhibited predominately normal heart
      looping, even when they formed the right twin. Taken together, these results
      indicate that LR asymmetry is locally oriented as a consequence of Wnt signaling
      through beta-catenin and Siamois. We discuss the possibility that signals
      upstream of beta-catenin and Siamois might be required in order for a right
      sibling to be randomized.

PMID- 9281339
TI  - Spectrosomes and fusomes anchor mitotic spindles during asymmetric germ cell
      divisions and facilitate the formation of a polarized microtubule array for
      oocyte specification in Drosophila.
AB  - In the Drosophila ovary, membrane skeletal proteins such as the adducin-like Hts
      protein(s), spectrin, and ankyrin are found in the spectrosome, an organelle in
      germline stem cells (GSC) and their differentiated daughter cells (cystoblasts).
      These proteins are also components of the fusome, a cytoplasmic structure that
      spans the cystoblast's progeny that develop to form a germline cyst consisting of
      15 nurse cells and an oocyte. Spectrosomes and fusomes are associated with one
      pole of spindles during mitosis and are implicated in cyst formation and oocyte
      differentiation. Here we show that the asymmetric behavior of the spectrosome
      persists throughout the cell cycle of GSC. Eliminating the spectrosome by the
      htsl mutation leads to randomized spindle orientation, suggesting that the
      spectrosome anchors the spindle to ensure the asymmetry of GSC division;
      eliminating the fusome in developing cysts results in defective spindles and
      randomized spindle orientation as well as asynchronous and reduced cystocyte
      divisions. These observations suggest that fusomes are required for the proper
      formation and asymmetric orientation of mitotic spindles. Moreover, they
      reinforce the notion that fusomes are required for the four synchronous divisions
      of the cystoblast leading to cyst formation. In htsl cysts which lack fusomes and
      fail to incorporate a hts gene product(s) into ring canals following cyst
      formation, polarized microtubule networks do not form, the dynamics of
      cytoplasmic dynein is disrupted, and oskar and orb RNAs fail to be transported to
      the future oocyte. These observations support the proposed role of fusomes and
      ring canals in organizing a polarized microtubule-based transport system for RNA
      localization that leads to oocyte differentiation.

PMID- 9281340
TI  - Cloning and characterization of chicken Paraxis: a regulator of paraxial mesoderm
      development and somite formation.
AB  - To investigate the molecular regulation of embryonic somite formation and
      development, we have cloned the full-length cDNA and characterized the embryonic
      expression profile of chicken Paraxis, a member of a novel family of basic helix
      loop-helix (bHLH) proteins, which has been suggested to play a role in paraxial
      mesoderm development. Chicken Paraxis encodes a 1.35-kb mRNA and contains a 53
      amino-acid residue bHLH domain, identical in sequence to that found in the
      mammalian Paraxis genes of mouse, hamster, and human. Northern analysis revealed
      significant Paraxis expression in the early embryo up to the 30- to 35-somite
      stage, declining from Incubation Day 4 on and becoming undetectable by Day 5. By
      whole-mount in situ hybridization, Paraxis expression is first seen distinctly in
      the emerging paraxial mesoderm of the primitive streak stage chick embryo. During
      gastrulation, Paraxis expression in the mesoderm defines bilaterally symmetric
      crescents located immediately rostral to Hensen's node and appears to pre
      configure the emerging somitic mesoderm. During somite development, Paraxis
      expression is evident in the rostral segmental plate and the newly formed
      somites, although the level of expression clearly decreases in the more mature
      somites. By the 10-12th pair of somites, counting from the caudal end, Paraxis
      expression appears to be preferentially localized to the medial aspect of
      individual somites. Histological analysis showed that Paraxis expression is
      evenly distributed in the newly formed caudal epithelial somites, then localized
      to the medial portion of maturing somites, and preferentially localized in the
      dermomyotome of more rostral somites before diminishing to undetectable levels in
      the most cranial somites. The functional involvement of Paraxis in somite
      development was assessed by perturbing its expression in somitic stage chick
      embryos using a Paraxis-specific antisense oligonucleotide. Disruption of somite
      formation from the paraxial mesoderm was observed in 67% of the surviving
      topically treated embryos, whereas control embryos treated with sense or random
      sequence oligonucleotides did not show similar effects. In addition, direct
      injection of Paraxis-specific antisense oligonucleotide into the paraxial
      mesoderm produced discrete segmentation anomalies which correlated spatially with
      the site of injection. Whole-mount in situ hybridization revealed that the
      regions defective in somite formation displayed perturbed Paraxis expression and
      a reduction of Pax-1 expression, a marker for epithelial somites and sclerotome.
      Histological analysis indicated poor condensation and/or epithelization of the
      somitic mesoderm. Finally, embryos treated with valproic acid, a known teratogen
      which affects somite segmentation, showed perturbed Paraxis expression,
      suggesting that the mechanism of action of this teratogen involves a pathway(s)
      requiring Paraxis activity. These data provide evidence that Paraxis acts as an
      important regulator of paraxial mesoderm and somite development and functions in
      axial patterning of the chick embryo.

PMID- 9281341
TI  - Regulation of epidermal induction by BMP2 and BMP7 signaling.
AB  - The specification of neural fate in Xenopus embryos has been shown to be under
      regulation by negative factors. The secreted protein bone morphogenetic protein-4
      (BMP4) has been identified as one of these factors: in the early gastrula
      ectoderm, BMP4 can both inhibit neural fate and induce epidermis. In this study,
      we show that two other Xenopus BMP genes, BMP2 and BMP7, are endowed with the
      same types of activities. First, we show that expression of a dominant negative
      form of the BMP2 ligand, which blocks normal processing of the wild-type ligand,
      causes neuralization of Xenopus ectoderm. Second, we have isolated the Xenopus
      BMP2/7 receptor (XALK2) and generated a constitutively active mutant that signals
      in a ligand-independent manner. We show that signals from the activated BMP2/7
      receptor also inhibit neuralization and induce epidermis in dissociated ectoderm
      cells. Consistent with both findings we show that secreted BMP2 and BMP7 ligands
      can also mediate neural inhibition and epidermal induction. These results suggest
      that both BMP2 and BMP7 may be involved independently or together with BMP4 in
      the inhibition of the neural fate and the onset of the epidermal induction
      pathway in vivo. This further supports the idea that epidermal induction is due
      to the effects of multiple signals from heterogeneous BMP genes.

PMID- 9281342
TI  - An intrinsic dominant negative activity of serrate that is modulated during wing
      development in Drosophila.
AB  - The Serrate and Delta genes of Drosophila encode two transmembrane proteins that
      act as ligands for the Notch receptor. Both have been shown to promote Notch
      activity during wing development and the specification of cell fate during
      neurogenesis. This observation has led to the suggestion that Serrate and Delta
      are functionally equivalent ligands for Notch. In this study we compare the
      activities of these proteins during wing development. Our results show that
      Serrate can activate or inactivate Notch in a concentration-dependent manner.
      While the inactivation is likely to be mediated by a dominant negative effect
      over Notch, the activation is similar to that elicited by Delta and requires the
      product of the Suppressor of Hairless gene. These results indicate that
      regulation of the concentration of Serrate during development must be an
      important way of regulating its activity.

PMID- 9281343
TI  - Effect of fibroblast growth factors on outgrowth of facial mesenchyme.
AB  - The ectoderm is required for outgrowth of facial prominences and facial ectoderm
      from all facial prominences is interchangeable. Signals provided by the ectoderm
      may include members of the fibroblast growth factor family (FGF). In order to
      test whether FGFs could replace facial ectoderm and promote outgrowth, stage 24
      frontonasal mass or mandibular mesenchyme was grafted to a host chick limb and a
      bead soaked in FGF-2 or FGF-4 was placed on top of the mesenchyme. Following 7
      days of incubation, the amount of outgrowth was quantified by measuring the rods
      of cartilage that formed from the grafts. FGF-2 and FGF-4 stimulated an increase
      in length of cartilage rods in mandibular grafts compared to mandibular
      mesenchyme grafted without ectoderm (P < 0.05). FGF-4 stimulated a small increase
      in length of frontonasal mass mesenchyme (P < 0.05) and both FGFs increased the
      frequency of egg tooth formation in frontonasal mass mesenchyme compared to
      frontonasal mass mesenchyme grafted without ectoderm. FGFs can partially but not
      completely replace facial ectoderm since homotypic recombinations of frontonasal
      mass and mandibular tissues were significantly longer than mesenchyme grafts
      treated with FGF-soaked beads (P < 0.05). The addition of a second FGF-soaked
      bead did not significantly increase the length of the frontonasal mass or the
      mandibular mesenchyme. We have determined that FGF-2 protein is expressed in
      facial ectoderm and could be an endogenous signal for outgrowth. In contrast, FGF
      8 transcripts are not expressed in the ectoderm covering the areas of the face
      that were grafted; thus, it is less likely that FGF-8 is required for outgrowth.
      Our results indicate that FGFs are part of an endogenous signaling pathway
      involved in distal outgrowth and chondrogenesis of the facial prominences.

PMID- 9281344
TI  - Routes of Cl- transport across the trophectoderm of the mouse blastocyst.
AB  - The blastocyst stage of embryo development is characterized by a fluid-filled
      cavity called the blastocoel. Blastocoel formation requires vectorial Na+ and Cl-
      transport and the accompanying osmotic accumulation of fluid. We found under
      conditions of low external Cl- that inhibitors of Cl- transport mechanisms
      inhibited blastocoel expansion, indicating a possible transcellular route for Cl-
      uptake across the outer epithelial layer (the trophectoderm). Using the Cl-
      sensitive fluorophore, N-(6-methoxyquinolyl)acetoethyl ester, we found that Cl-
      efflux from the blastocoel can occur via pathways with properties that resemble
      both HCO-3/Cl- exchange and Cl- channels, as well as by another yet
      uncharacterized pathway. In contrast, Cl- re-uptake into Cl--depleted blastocoels
      (the physiologically relevant direction for Cl- transport during blastocoel
      expansion) occurred only via the channel-like mechanism. Patch-clamp recordings
      detected a component of current carried by apical Cl- channels. Intracellular pH
      measurements during external Cl- removal detected HCO-3/Cl- exchange activity in
      collapsed blastocysts but little in intact blastocysts, suggesting predominantly
      basolateral HCO-3/Cl- exchange activity. This was corroborated by the
      immunolocalization of the AE2 isoform of HCO-3/Cl- exchanger to the basolateral
      surface of the trophectoderm. Thus, it appears that Cl- transport into the
      blastocoel may occur via apical Cl- channels, while efflux also involves a
      basolateral HCO-3/Cl- exchanger.

PMID- 9281346
TI  - Expression of OCI-5/glypican 3 during intestinal morphogenesis: regulation by
      cell shape in intestinal epithelial cells.
AB  - OCI-5, the rat homologue of human glypican 3 (GPC3), is believed to be involved
      in morphogenesis and growth control during development. The finding that GPC3 is
      mutated in patients with the Simpson-Golabi-Behmel overgrowth syndrome is
      consistent with this idea. In this report, using RNA in situ hybridization,
      expression of OCI-5 in the developing intestine is detected in both endoderm- and
      mesenchyme-derived cells in a phased manner related to age and proximal/distal
      position. To investigate the mechanism of its regulation during intestinal
      development, OCI-5 expression was studied in the primitive rat intestinal
      epithelial cell line IEC-18. The expression of the OCI-5 transcript is increased
      in IEC-18 cells at confluence, in low calcium media, and during spheroid culture,
      all conditions which result in the cells acquiring a more rounded cell shape. In
      contrast, cytoskeletal disruption with colchicine causes cells to flatten and
      spread and abolishes both the confluence- and the low calcium-dependent induction
      of OCI-5. Treatment with vanadate, a phosphatase inhibitor, causes cells to
      acquire a spindle-shaped morphology and prevents OCI-5 induction in all
      situations. Nuclear run-on analysis demonstrates that the rate of OCI-5
      transcription is increased at confluence, in low calcium media, and during
      spheroid culture of IEC-18, and decreased by treatment of cells with colchicine.
      Together, these data suggest that OCI-5 expression is regulated in IEC-18 by cell
      shape. The pattern of expression of OCI-5 in the developing intestine is
      consistent with it playing a role in epithelial-mesenchymal interactions during
      intestinal morphogenesis, when cell shape changes are likely to occur.

PMID- 9281347
TI  - Human intervertebral disc cells from the annulus: three-dimensional culture in
      agarose or alginate and responsiveness to TGF-beta1.
AB  - Cell culture procedures were developed for use with surgical and normal control
      specimens of the annulus of the human intervertebral disc. Cells were established
      in monolayer explant culture and seeded into three-dimensional growth
      environments of alginate or agarose; under these growth conditions cells assumed
      a rounded phenotype and formed colonies. A novel method of layering suspensions
      of cells onto cell well inserts proved technically much easier than the microbead
      culture method. Immunohistochemistry was utilized to demonstrate in vitro
      production of the following extracellular matrix components: types I, II, III,
      and VI collagen, 4-S-chondroitin sulfate, and keratan sulfate. Young and old age-
      and gender-matched cells grown in the presence of TGF-beta1 showed significant
      enhancement of proliferation after 4 days of exposure to TGF-beta with a lessened
      mitogenic response present after 10 days. Molecular studies of proteoglycan gene
      expression showed that at 4 days young normal cells had increased biglycan, but
      not decorin, message levels. Decorin expression was unchanged at Day 4 and
      decreased or shut off by Day 10. Results support the use of three-dimensional
      culture systems for in vitro evaluation of human disc cell function and expand
      our understanding of the in vitro behavior of these cells.

PMID- 9281348
TI  - Cell-matrix interactions induce tyrosine phosphorylation of MAP kinases ERK1 and
      ERK2 and PLCgamma-1 in two-dimensional and three-dimensional cultures of human
      fibroblasts.
AB  - Using immunoprecipitation and phosphotyrosine detection by Western blotting,
      intracellular signaling intermediates were analyzed in human primary dermal
      fibroblasts, either seeded as monolayers on collagen I coats (2D) or seeded
      within three-dimensional collagen I lattices (3D). Previous results demonstrated
      that integrin activation in these systems resulted in a cascade of protein
      tyrosine phosphorylation, including focal adhesion kinase (D. Roeckel and T.
      Krieg, 1994, Exp. Cell Res. 211, 42-48). Further downstream signaling events are
      now shown to include coordinate activation of ERK1 and ERK2 at 2 h after cell
      collagen contact, irrespective of 2D or 3D culture conditions. Applying U-73122,
      an inhibitor of PLC, inhibits collagen lattice contraction in a dose-dependent
      fashion. Immunoprecipitation identified the isoform PLCgamma-1 as playing a role
      as signaling intermediate in fibroblast-collagen interactions. PLCgamma-1 becomes
      phosphorylated within 10 min after culture initiation and declines after 2 h. So
      far, no qualitative differences in signaling intermediates between 2D and 3D
      cultures have been identified.

PMID- 9281349
TI  - A factor with a zinc- and phorbol ester-binding domain is necessary for endosome
      fusion.
AB  - An inhibitory effect of several zinc chelators on endosome fusion reconstituted
      in an in vitro system has been recently reported (A. Aballay et al., 1995,
      Biochem. J. 312, 919-923). The factor that requires zinc for its activity is
      still unknown. Since the regulatory domain of protein kinase C (PKC) contains
      cysteine-rich motifs which coordinate zinc, we suspected that PKC or a PKC-like
      protein might be that factor. To test this hypothesis, we studied the effect of
      calphostin C, a specific inhibitor of PKC that interacts with the cysteine-rich
      motif, and PMA (phorbol 12-myristate 13-acetate), an activator of several PKC
      isoforms that bind to the same region, on endosome fusion. Calphostin C inhibited
      endosome fusion in a zinc-regulated manner, whereas PMA enhanced endosome fusion.
      Moreover, fusion was strongly stimulated when both PMA and zinc were added
      together to zinc-depleted fusion reactions. Inhibitors of the catalytic domain of
      PKC had no effect on the assay suggesting that the kinase activity is not
      required. In contrast, a glutathione S-transferase fusion protein containing a
      cysteine-rich region of the regulatory domain of PKCgamma inhibited endosome
      fusion in a PMA-dependent manner. Western blot analysis demonstrated the presence
      of proteins containing PKC-like cysteine-rich regions that are released from
      endosomal fractions by zinc chelators. These results indicate that the previously
      proposed zinc-dependent factor required for endosome fusion could be either a PKC
      isoform or a protein containing the phorbol ester-binding domain of PKC.

PMID- 9281350
TI  - Characteristics of 25-hydroxycholesterol-induced apoptosis in the human leukemic
      cell line CEM.
AB  - Cholesterol and related compounds can give rise to oxygenated sterol molecules
      (oxysterols) which are potent regulators of lymphoid cell growth. Oxysterols
      added exogenously cause cell death of several lines of cultured cells, and on the
      basis of limited criteria, it has been suggested that this death is apoptosis. In
      the present study, we show definitive evidence that 25-hydroxycholesterol (25OHC)
      kills cells of the clone CEM-C7 by apoptosis and establish the temporal sequence
      of related cellular and biochemical events. Cell shrinkage was evident as early
      as 12 h, while cell death was not evident until after 24 h. It mounted rapidly
      after that, and by 72 h, virtually all cells were dead. Electron microscopic
      analysis shows that by 24 h after treatment and before the onset of cell death,
      early ultrastructural features typical of apoptosis were present. DNA breaks were
      detected by TUNEL assay prior to the onset of cell death. Two types of specific
      DNA pieces often associated with apoptosis were found as increasing numbers of
      cells died. DNA fragments of 300 and 50 kbp were not appreciable until 42 h, and
      internucleosomal cleavage was observed by 48 h after oxysterol addition. None of
      these effects were seen in an oxysterol-resistant CEM subclone, establishing the
      specificity for apoptosis of the biochemical and morphological events. z-VAD.FMK,
      a peptide inhibitor of ICE-related proteases delayed but did not prevent the
      apoptosis of CEM-C7 cells induced by 25OHC. The addition of mevalonate partially
      protected CEM-C7 cells from apoptosis but did not restore cell growth.

PMID- 9281351
TI  - Induction of apoptosis and potentiation of TNF- and Fas-mediated apoptosis in
      U937 cells by the xanthogenate compound D609.
AB  - Apoptosis induced by ligation of either the tumor necrosis factor (TNF) p55
      receptor or the Fas/APO-1/CD95 receptor has been suggested to require ceramide as
      a signaling molecule. Ceramide is formed as a result of sphingomyelinase (SMase)
      activation in the sphingomyelin cycle, and ligation of TNF and Fas receptors has
      been reported to stimulate SMase activity. We have studied the effects of D609, a
      xanthogenate compound with antitumoral properties, on TNF- or Fas-induced
      apoptosis of monocytic U937 cells. First, the effects of D609 on SMase activity
      were assessed using in vitro assays for neutral and acidic SMase, and the results
      suggested that D609 caused a modest stimulation of the activity of both SMases in
      U937 cells. Exposure of U937 cells for 6 h to TNF or anti-Fas mAb induced
      apoptosis in 40-45% of the cells, as measured by fluorescent staining of nuclear
      chromatin. Cotreatment with D609 potentiated TNF- as well as Fas-mediated
      apoptosis up to 70 and 90%, respectively. Furthermore, in incubations with D609
      alone, 60% of the cells became apoptotic within 16 h. Since D609 has been
      reported to inhibit protein kinase C (PKC) activity, the effect of phorbol 12
      myristate 13-acetate (PMA) on D609-induced apoptosis was investigated. PMA was
      found to inhibit D609-induced apoptosis in U937 cells as well as cell death
      induced by TNF and anti-Fas mAb. Thus, PKC inactivation may play an important
      role in the regulation of apoptosis in U937 cells. In summary, the present
      results show that D609 stimulates SMase activity, potentiates TNF- and Fas
      induced apoptosis, and induces apoptosis on its own in U937 cells.

PMID- 9281352
TI  - Retinoic acid receptors alpha and gamma mediate the induction of "tissue"
      transglutaminase activity and apoptosis in human neuroblastoma cells.
AB  - All-trans retinoic acid (RA) reduces human neuroblastoma growth by inducing
      either differentiation or apoptosis. The apoptotic program in these cells is
      regulated by RA and is paralleled by the transcriptional induction of "tissue"
      transglutaminase (tTG). tTG is a protein cross-linking enzyme, which specifically
      accumulates in cells undergoing apoptosis in various in vivo and in vitro
      systems. In neuroblastoma cells, tTG is detected exclusively in the cells
      expressing the S-type phenotype and showing an increased apoptosis. The present
      study was undertaken to identify the retinoid receptors which are involved in the
      regulation of tTG and apoptosis as well as in the in vitro neuronal
      differentiation of the human SK-N-BE(2) neuroblastoma cell line. We have
      previously characterized the retinoid acid receptors expressed in this cell line.
      In the present study, by using synthetic retinoids selectively activating RAR/RXR
      isoforms, we have identified the RAR/RXR receptors involved in the induction of
      either apoptosis or differentiation. We have also studied the effect of the
      selective RA analogs on tTG activity. We observed that while RARalpha- and
      RARgamma-selective retinoids alone were able to induce tTG activity, only the
      combined stimulation of both RARalpha and RARgamma induced apoptosis. Conversely,
      several combinations of RAR/RXR closely mimicked the differentiation effects
      observed with all-trans retinoic acid. These results indicate that, at variance
      with differentiation, the induction of apoptosis in human SK-N-BE(2)
      neuroblastoma cells is under the specific control of RARalpha and RARgamma. These
      data seem relevant for the reported ability of RARgamma to suppress the
      clinically malignant tumor phenotype in patients.

PMID- 9281353
TI  - Thyroid cell transformation inhibits the expression of a novel rat protein
      tyrosine phosphatase.
AB  - We have isolated a rat thyroid cDNA encoding a novel rat receptor-type tyrosine
      phosphatase protein. This gene, on the basis of its homology to another tyrosine
      phosphatase, the recently isolated human DEP-1/HPTPeta, has been named r-PTPeta.
      In rat thyroid cells the r-PTPeta gene acts as a differentiation marker. Indeed,
      the block of thyroid cell differentiation induced by viral and cellular oncogenes
      is associated with the inhibition or marked reduction of the expression of this
      gene, and its expression is positively regulated by thyrotropin, the
      physiological stimulator of thyroid cell growth.

PMID- 9281355
TI  - MHC class II-associated invariant chain-induced enlarged endosomal structures: a
      morphological study.
AB  - The major histocompatibility complex class II-associated invariant chain is
      believed to direct newly synthesized class II to endocytic compartments.
      Invariant chain synthesized at high levels in transiently transfected cells
      induces formation of large vesicular structures. We have examined the effect of
      stable expression of invariant chain in human fibroblasts by light and electron
      microscopy. Invariant chain expression dramatically modified endocytic
      compartments and induced the formation of greatly enlarged structures. These
      modifications were not lethal. Ultrastructurally, at least three morphologically
      distinct enlarged compartments could be discerned in the cells. These three
      compartments may represent early and late endosomes and lysosomes.
      Internalization of anti-invariant chain antibodies shows that invariant chain may
      reach the large endosomes via rapid internalization from the plasma membrane.
      Internalized protein remained in the enlarged vesicles for 4-6 h, indicating an
      invariant chain-induced delay in the pathway to lysosomes. Although the large
      invariant chain-induced vesicles have not yet been seen in professional antigen
      presenting cells, the invariant chain-induced effects may play a role in
      regulating the endocytic pathway, creating a special environment for MHC class II
      to bind antigen.

PMID- 9281354
TI  - Molecular cloning and characterization of a novel mitochondrial phosphoprotein,
      MIPP65, from rat liver.
AB  - A novel 65-kDa protein (designated MIPP65), which was phosphorylated by PKN in
      vitro in a manner highly dependent on arachidonic acid, was partially purified
      from the heat-stable proteins extracted from a 30,000g precipitate of rat liver.
      The cDNA clones were obtained by polymerase chain reaction using oligonucleotides
      based on partial amino acid sequences. The complete amino acid sequence deduced
      from the cDNAs contained two homologous regions with the mitochondrial NADH
      ubiquinone oxidoreductase 9-kDa subunit precursor at the amino- and carboxyl
      termini, whereas the central region was not related to any known proteins and
      contained a serine cluster. Northern blotting and immunoblotting analyses
      indicated that MIPP65 was expressed ubiquitously in rat tissues.
      Immunofluorescence analysis of the endogenous MIPP65 using polyclonal antiserum
      against MIPP65 showed a predominantly mitochondrial localization in C6 glioma
      cells. The recombinant MIPP65 expressed in COS7 cells showed a similar pattern of
      localization to that in C6 glioma cells. On the other hand, deletion of the amino
      terminal region of MIPP65 abrogated such localization, indicating that the amino
      terminal region contained a mitochondrial-targeting signal. From
      [32P]orthophosphate-labeled C6 glioma cells, the endogenous MIPP65 could be
      immunoprecipitated as a phosphoprotein with antiserum against MIPP65. These
      results suggest that MIPP65 is a novel mitochondrial phosphoprotein that is a
      candidate substrate for PKN.

PMID- 9281356
TI  - Natural occurrence of fast- and fast/slow-muscle chimeric fibers in the
      expression of troponin T isoforms.
AB  - Rhomboideus, one of the back muscle tissues, and its single fibers were studied
      in chickens by immunostaining with antisera against fast- and slow-muscle-type
      troponin T isoforms. Nonuniform distribution of slow-muscle-type isoforms was for
      the first time detected in single fibers isolated from the muscle, although fast
      muscle-type troponin T isoforms were distributed over the whole length of the
      fiber. Based on these observations, we conclude that fast- and fast/slow-muscle
      chimeric fibers exist in normal skeletal muscle tissue and that the existence of
      chimeric fibers is direct evidence showing that myonuclei subjected to different
      determination in troponin T isoform expression can together form a single muscle
      fiber.

PMID- 9281357
TI  - O-Glycosylation and cellular differentiation in a subpopulation of mucin
      secreting HT-29 cell line.
AB  - Malignant transformation of epithelial cells is associated with abnormal
      glycosylation of mucins. The aim of this work was to evaluate the changes in the
      O-glycosylation processes during differentiation of tumor cells by performing in
      vitro reactions using crude microsomal preparations obtained from a subpopulation
      of HT-29 cells capable of differentiating into mucin-secreting cells (HT-29 MTX
      cells). The reactions of O-glycosylation were carried out at different times of
      culture: before confluence (Day 5), when cells are still undifferentiated, and
      after confluence (Day 21), when cells display a mucin-secreting phenotype. As
      acceptor for the UDP-N-acetylgalactosamine:polypeptide
      Nacetylgalactosaminyltransferase (GalNAc transferase), the peptide motif TTSAPTTS
      (tandem repeat deduced from MUC5AC human gastric gene, expressed in HT-29 MTX
      cells) was used. A higher rate of enzyme activity was observed in preconfluent
      cells, and analysis by capillary electrophoresis and electrospray mass
      spectrometry showed a different pattern of galactosaminylation in pre- and
      postconfluent cells. Core 1 UDP-galactose:N-acetyl-alpha-galactosaminyl-R 3-beta
      galactosyltransferase (3-beta-galactosyltransferase) activityalso decreased with
      the differentiation, whereas CMP-neuraminic acid:galactose-beta-1, 3-N-acetyl
      alpha-galac- tosaminyl-R 3-alpha-sialyltransferase activity increased. In
      comparison, the evolving process of mucin biosynthesis was tested by the analysis
      of purified mucins of HT-29 MTX cells, in amino acid and carbohydrate
      composition, and immunoreactivity assays using several antibodies and lectins.
      The results suggested that (i) no mucins were detected at Day 5, while the GalNAc
      transferase and 3-beta-galactosyltransferase activities were already at high
      rates; (ii) the mucins purified from postconfluent cells showed a high content of
      sialic acid in an alpha-2,3-linkage to galactose residues; and (iii) cellular
      differentiation seemed to be accompanied by more regulated processes of
      glycosylation. This study of the O-glycosylation in HT-29 MTX cells is thus an
      interesting approach to analyzing the regulation of mucin biosynthesis during
      cellular differentiation.

PMID- 9281358
TI  - Priming of mouse macrophages with the macrophage colony-stimulating factor (CSF
      1) induces a variety of pathways that regulate expression of the interleukin 6
      (Il6) and granulocyte-macrophage colony-stimulating factor (Csfgm) genes.
AB  - Recent data have indicated that resident mouse peritoneal macrophages (PMo)
      transcribed the interleukin 6 (Il6) and granulocyte-macrophage colony-stimulating
      factor (Csfgm) genes in response to stimulation with the monocyte-macrophage
      colony-stimulating factor (CSF-1) but only Il6 mRNA was translated into secreted
      protein. In this paper, we extend these observations. It is shown that resident
      PMo incubated with protein kinase (PK)C inhibitors, staurosporine (SP) and its
      derivative GF109203-X, showed a several fold increase in the levels of Il6 mRNA
      in control and CSF-1-primed PMo and a parallel release of large amounts of
      protein. In contrast, SP was shown to have no effect on the release of GM-CSF
      from control or CSF-1-primed PMo, although it increased by approximately twofold
      the amount of Csfgm mRNA in CSF-1-primed Mo. When SP was added 4 h after CSF-1
      priming to block CSF-1-induced protein kinase pathways, an increased amount of IL
      6 release was again seen but without any increase in Il6 mRNA levels. Under these
      conditions, Csfgm gene expression was relatively unaffected. Activation of PKC by
      phorbol myristate acetate (PMA) also resulted in increased Il6 gene expression by
      control and CSF-1-primed PMo. PMA had no apparent effect on Csfgm transcription
      but appeared to influence translation at a low level, as measured by the release
      of small amounts of GM-CSF protein. The addition of lipopolysaccharide (LPS) to
      CSF-1-primed PMo resulted in a synergistic increase in the expression of both
      genes at the levels of transcription and protein release. The addition of SP to
      CSF-1-primed Mo before LPS, however, further enhanced IL-6 release but not GM-CSF
      release from the cells. The data indicate that CSF-1-priming drives a number of
      pathways involved in the regulation of expression of both genes and renders PMo
      highly susceptible to appropriate secondary stimulatory agents that transform the
      PMo into secretory inflammatory cells.

PMID- 9281359
TI  - The Ras Guanine nucleotide Exchange Factor CDC25Mm is present at the synaptic
      junction.
AB  - CDC25Mm, a mouse Ras-Guanine nucleotide Exchange Factor, is specifically
      expressed as a product of 140 kDa (p140) in the postnatal and adult brain.
      Immunohistochemical analysis indicates that it is present throughout the brain
      particularly concentrated in discrete punctate structures. Subcellular
      fractionation of the mouse brain shows that p140 is present in synaptosomes but
      not in highly purified synaptic vesicles. Moreover, isolated postsynaptic
      densities (PSDs) are largely enriched in CDC25Mm. This protein can be
      phosphorylated by calcium/calmodulin kinase II, the most abundant protein in
      PSDs. Altogether these results suggest that CDC25Mm is present at synaptic
      junctions and that it may be involved in synaptic signal transduction leading to
      Ras activation.

PMID- 9281360
TI  - Inhibitors of protein kinases abolish ECM-mediated promotion of neuronal
      polarity.
AB  - Different extracellular matrix (ECM) molecules, when presented to hippocampal
      neurons in culture in a substrate-bound form, exert strikingly similar effects on
      the establishment of neuronal polarity, i.e., the growth of axon-like major
      neurites is favored, whereas extension of dendrite-like minor neurites is
      inhibited. To gain insight into the underlying signal transduction processes, we
      have investigated the effects of modulators of protein kinase activity on the
      morphology of neurons cultured on tenascin-R, tenascin-C, and laminin-entactin
      substrates. We found differential effects of broad-spectrum protein kinase
      inhibitors: H-7 promoted the growth of minor neurites, whereas H-8 reduced the
      growth of major neurites on ECM but not control substrates. In contrast,
      chelerythrine, a specific inhibitor of protein kinase C, selectively affected
      growth of both minor and major neurites on control, but not on ECM substrates.
      Finally, reagents which elevate intracellular cAMP levels facilitated growth of
      minor neurites and inhibited growth of major neurites and thus interfered with
      the establishment of a polarized phenotype on both ECM and control substrates.
      Our results suggest that protein kinases mediate the effects of ECM molecules on
      neuronal polarity and that different kinases control extension of axons and
      dendrites.

PMID- 9281361
TI  - The cleavage of nuclear DNA into high molecular weight DNA fragments occurs not
      only during apoptosis but also accompanies changes in functional activity of the
      nonapoptotic cells.
AB  - In this paper we demonstrate that apoptosis in primary culture of murine
      thymocytes and in continuously growing human cells is associated with the
      progressive disintegration of nuclear DNA into high molecular weight (HMW)-DNA
      fragments of about 50-150 kb. We also show that the formation of similarly sized
      HMW-DNA fragments takes place in the same cells in the absence of apoptotic
      inducers. Unlike an apoptotic fragmentation of nuclear DNA, the formation of HMW
      DNA fragments in nonapoptotic cells is rapidly induced, has no correlation with
      the cell death, and is not associated with the development of oligonucleosomal
      "ladder" or apoptotic changes in nuclear morphology. The disintegration of DNA
      into HMW-fragments is also observed in nuclei isolated from healthy,
      nonapoptosizing tissues of various eukaryotes. We show that the formation of HMW
      DNA fragments in the absence of apoptotic inducers is strongly dependent on the
      ionic detergents, is responsive to the topoisomerase II-specific poison,
      teniposide, and is completely reversible under conditions that favor
      topoisomerase II-dependent rejoining reaction. Also, we demonstrate that the
      formation of HMW-DNA fragments in continuously growing cell lines caused either
      by serum deprivation or monolayer establishment is of a transient nature and
      rapidly reverses to the control level following serum addition or dilution of
      monolayer. The results suggest that the cleavage of nuclear DNA into HMW-DNA
      fragments is associated not only with apoptosis but also accompanies changes in
      functional activity of nonapoptotic cells.

PMID- 9281362
TI  - Apoptosis-resistant phenotype selected by alternating exposure to camptothecin
      and etoposide.
AB  - We selected an apoptosis-resistant subline (VC-33) in a human promyelocytic
      leukemia cell line, HL-60, by alternating exposure to camptothecin (CPT) and
      etoposide (VP-16). When wild-type (WT) and VC-33 cells were incubated with
      various concentrations of either CPT or VP-16 for 4 h, VC-33 showed several-fold
      resistance to apoptosis induced by these agents in comparison with WT cells. VC
      33 cells also exhibited cross-resistance to apoptosis induced by 1-beta-d
      arabinofuranosylcytosine, hydroxyurea, a calcium ionophore (A23187),
      cycloheximide, or UV irradiation. The levels of protein-DNA cross-linking induced
      by CPT or VP-16, and the amounts of ara-CTP generation, tended to be smaller in
      VC-33 cells, but the difference was not sufficient to explain the difference in
      the sensitivity to apoptosis. The initial rise of intracellular calcium ions with
      A23187 and the expression of P-glycoprotein, Bcl-2, and Bcl-Xl were comparable
      between WT and VC-33 cells. This mutant may represent a new phenotype of
      resistance to apoptosis induced by a variety of agents, and may thus be useful in
      the study of the mechanisms of apoptosis.

PMID- 9281363
TI  - N-Myristoyltransferase overexpression in human colorectal adenocarcinomas.
AB  - Modification of proteins by myristoylation has been proposed as a
      chemotherapeutic target against colon cancer because it is important in the
      function of various signal transduction proteins. Recently we reported that the
      enzyme that catalyzes this modification, N-myristoyltransferase (NMT), is
      elevated in colorectal adenocarcinomas [Magnuson, B. A., Raju, R. V. S., Moyana,
      T. N., and Sharma, R. K. (1995) J. Natl. Cancer. Inst. 87, 1630-1635]. The
      purpose of the present study was to investigate whether the elevated activity of
      NMT in colorectal adenocarcinomas is due to an increase in the production of NMT
      or a change in the structure of the preexisting enzyme. The expression of NMT in
      normal colonic mucosa and adenocarcinomas from human colorectal surgical
      specimens was studied by immunoblotting, and its localization was confirmed by
      immunohistochemistry. The molecular weight of NMT was determined by fast protein
      liquid chromatography. In both normal mucosa and colorectal adenocarcinomas, NMT
      with a molecular mass of 48.5 kDa was identified with anti-human NMT and anti
      peptide antibody. However, the expression of NMT was found to be higher in the
      colorectal tumors. This finding was further confirmed by immunohistochemical
      studies which showed stronger cytoplasmic staining in the tumors. These findings
      represent the first description of NMT overexpression in colorectal
      adenocarcinomas. This has implications with regard to (i) the design of
      chemotherapeutic drugs and (ii) prognosis, for instance, in monitoring colorectal
      cancer recurrence or metastases.

PMID- 9281364
TI  - Pressure-induced apoptosis in human lymphoblasts.
AB  - The viability of human lymphoblasts was investigated after compression at 37
      degrees C for 30 min. Immediately after decompression, necrotic cells were
      observed and the viability decreased sigmoidally to 0 with increasing pressure
      from 85 to 200 MPa. Apoptotic cells began to be observed from 8 h after
      decompression in the case of compression at 100 MPa for 30 min at 37 degrees C.
      The apoptosis was confirmed to be pressure-induced by the Tunel method and by
      optical and electron microscopy. Cell death by both necrosis and apoptosis due to
      compression was accelerated in the S phase of the cell cycle.

PMID- 9281365
TI  - A longitudinal study of human age-related chromosomal analysis in skin
      fibroblasts.
AB  - Previous chromosomal analyses related to human aging used mainly cross-sectional
      data on metaphase chromosomes. However, it is difficult to directly relate the
      cross-sectional results to the specific type(s) of chromosomal mutations possibly
      occurring within a specific individual with advancing age, because the unique
      genetic endowment of each individual for longevity might be a modulating factor.
      We therefore have performed, for the first time, a longitudinal study of both
      numerical and structural chromosome analyses of skin fibroblasts at interphase
      and at metaphase derived from eight donors participating in the Baltimore
      Longitudinal Study. We have used the FISH method with chromosome-specific DNA
      probes and the data on total aneuploidy of 17 different chromosomes in each of
      the 16 cell cultures (2 from each of eight individuals) indicate that
      significantly higher percentages of aneuploid cells are detected at interphase
      than at metaphase. Mostly, the levels of chromosome-specific aneuploidy increase
      with the donor's advancing age and, in most individuals, chromosomes 1, 4, 6, 8,
      10, and 15 show significantly higher frequencies of aneuploidy at interphase than
      those of the 11 other chromosomes studied. Although the significance of
      relatively higher levels of aneuploidy of certain chromosomes with aging remains
      unclear, it is intriguing to note that some of these chromosomes, such as 1, 4,
      and 6, have already been assigned to harbor senescence genes and chromosome 8 is
      known to house the gene for Werner Syndrome (progeroid syndrome), which shows
      very limited proliferative capacity of fibroblasts. It is conceivable that the
      degree and/or type of chromosome-specific aneuploidy might have some gene dosage
      effects in the control of cellular proliferation and selection during aging. We
      also show that a combination of both interphase and metaphase aneuploidy analyses
      provides more comprehensive and insightful information on intraindividual
      cellular dynamics and chromosomal aneuploidy as a function of age. Occasionally,
      very small proportions of cells in two individuals showed age-related structural
      chromosome aberrations, such as an acentric fragment derived from an X chromosome
      and an achromatic gap in chromosome 7. Thus, a comparative analysis of both intra
      and interindividual longitudinal studies is very useful in detecting the
      pattern(s) of chromosome-specific alterations with increasing age.

PMID- 9281366
TI  - Growth and differentiation factors inhibit the migratory phenotype of cultured
      neonatal rat hepatocytes induced by HGF/SF.
AB  - Previous studies have demonstrated that neonatal rat hepatocytes cultured in a
      serum-free medium adopt a fibroblast-like morphology and form a well-developed
      vimentin network. By immunoblotting, phase-contrast microscopy, and
      immunolocalization studies we report here that hepatocyte growth factor (HGF)
      induces a pronounced migratory/scatter phenotype in neonatal hepatocytes in
      primary culture. These fibroblast-like cells are highly elongated and adopt a
      pronounced spindle shape in the presence of this growth factor. Most of them
      coexpress vimentin and cytokeratin intermediate filaments. Both EGF and TGF-beta1
      also induced vimentin expression in cytokeratin-positive cells but this effect
      was not correlated with a change of epithelial phenotype. Only in DMSO
      supplemented cultures was vimentin expression of hepatocytes inhibited and no
      coexpression was observed in the presence of this factor. Remarkably, the effect
      induced by HGF was totally inhibited when DMSO, TGF-beta1, or EGF was added to
      HGF-supplemented cultures. Epithelial sheets of well-defined hepatocytes were
      observed with these combinations although the complete epithelial morphology was
      achieved by combining DMSO with a growth factor. Taken together these results
      suggest that growth and differentiation factors modulate the migratory effect of
      HGF/SF in hepatocytes.

PMID- 9281367
TI  - Fibroblasts can modulate the phenotype of malignant epithelial cells in vitro.
AB  - An organotypic, tridimensional cell culture, also called a raft system, was used
      to study the influence of fibroblasts on epithelial carcinogenesis in a cell line
      derived from laryngeal squamous cell carcinoma and harboring a mutated p53.
      Differences between the effects of normal fibroblasts and those of tumor-derived
      fibroblasts were compared by means of fibroblasts taken from the normal skin and
      from the tumor of a cancer patient and cultivated with epithelial carcinoma cells
      in an organotypic culture. To study cell contact-mediated changes, the
      fibroblasts were either simply embedded in collagen matrix or additionally
      brought into direct contact with epithelial cells. Control epithelial cells were
      cultivated without any fibroblasts in an organotypic model. A protein panel [p53,
      p21, PCNA, bcl-2, Ki67, total cytokeratin (CK), CK 8, CK 10, CK 17, CK 18, CK 19,
      vimentin] involved in cell cycling and epithelial differentiation was assessed
      immunocytochemically in all organotypic cultures with fibroblasts, in tumor cells
      cultivated as a monolayer, and in the original tumor sample. The most dysplastic
      phenotype was obtained when tumor-derived fibroblasts were used in direct contact
      with epithelial cells, whereas the most benign phenotype was seen when skin
      fibroblasts had no contact with them. The intensive staining seen for p53 can be
      explained by p53 mutations also reflecting the weak expression of p21 and
      abundant expression of PCNA. The intensive Ki67 staining seen in all sections
      paralleled that of PCNA and marked active cellular proliferation. The CK staining
      pattern seen in cultured epithelia toward embryonic CKs, CK 8 and CK 18,
      suggested a simple epithelial phenotype. CK 19 was found only in the epithelium
      where no direct contacts had occurred. Vimentin expression increased when the
      raft epithelium was shifting toward a more benign phenotype. The results stress
      the importance of the origin of fibroblasts as well as the role of direct
      cellular contacts in modifying the epithelial phenotype even when the epithelial
      cells are malignant.

PMID- 9281368
TI  - v-Ras and v-Raf block differentiation of transformable C3H10T1/2-derived
      preadipocytes at lower levels than required for neoplastic transformation.
AB  - To investigate the functional relationship between the transforming ability of
      Ras and its role as an integral component of the differentiative insulin
      signaling pathway, we introduced a leu61-activated ras gene into a Ras
      transformable, C3H10T1/2-derived preadipocytic cell line. The results demonstrate
      that rasleu61 expression in this line blocks differentiation and that this block
      appears at lower levels than required for full neoplastic transformation. In
      addition, to examine whether the inability of Rasleu61 to induce differentiation
      by replacing the insulin signal could be attributed to its transforming effect in
      this system, we examined the effect of Rasleu61 at levels below the baseline, by
      expressing rasleu61 in a series of preadipocytes which were rendered deficient in
      endogenous c-Ras activity. The results show that even very low Rasleu61 levels,
      insufficient to restore the growth rate of these cells to normal, blocked rather
      than enhanced differentiation, indicating that rasleu61 expression alone is not
      sufficient to promote adipocytic differentiation in this system, even in the
      absence of neoplastic transformation. Consistent with its established role as a
      downstream effector of Ras, v-Raf expression mirrored the v-Ras effects upon
      adipocytic differentiation and transformation.

PMID- 9281369
TI  - Insulin-like growth factor-1 receptor and its ligand regulate the reentry of
      adult ventricular myocytes into the cell cycle.
AB  - To determine whether insulin-like growth factor-1 (IGF-1) stimulation in vitro of
      ventricular myocytes isolated from infarcted hearts is characterized by the
      reentry of cells into the cell cycle, the expression and kinase activity of
      cyclins E, A, and B and DNA synthesis were evaluated 5 days after coronary artery
      occlusion and 24 and 48 h following the addition of IGF-1. Myocytes surviving an
      acute myocardial infarction were employed because of their increase in surface
      insulin-like growth factor-1 receptors (IGF-1R). Western blot analysis documented
      that IGF-1 resulted in an upregulation of cyclins D1, E, A, and B in viable
      postinfarcted myocytes. Cyclin E- and A-associated histone H1 kinase activity and
      cyclin D1-associated retinoblastoma protein-associated kinase activity also
      increased, but cyclin B kinase activity was not enhanced by IGF-1. These changes
      in cyclins and kinase activities were characterized by a significant increase in
      the number of cells labeled by bromodeoxyuridine, from approximately 630/10(6) to
      nearly 9, 000/10(6) myocytes. This latter value was reduced by more than 50% by
      antisense oligodeoxynucleotide to IGF-1R mRNA. However, IGF-1 stimulation did not
      induce nuclear mitotic division and cytokinesis. In conclusion, the growth
      promoting effect of IGF-1 on adult myocytes is regulated by the density of IGF
      1R, which conditions the activation of the replicatory machinery of the cells.
      The failure of IGF-1 to enhance cyclin B kinase activity may be responsible for a
      block in the cell cycle and the inability of myocytes to progress through the M
      phase and subsequently divide.

PMID- 9281371
TI  - Growth/differentiation factor-5 induces angiogenesis in vivo.
AB  - Bone morphogenetic proteins (BMPs) are multifunctional cytokines, which induce
      bone and cartilage formation and exert various other effects on many tissues.
      Since angiogenesis is involved in the bone formation process, certain members in
      the BMP family may induce angiogenesis. We examined the in vivo angiogenic
      activity of BMP family members, i.e., growth/differentiation factor (GDF)-5 and
      BMP-2. GDF-5 induced angiogenesis in both chick chorioallantoic membrane and
      rabbit cornea assays. In contrast, BMP-2 did not induce angiogenesis. In order to
      elucidate the mechanism of angiogenesis, we examined the effects of GDF-5 on
      cultured bovine aortic endothelial cells (BECs). GDF-5 induced plasminogen
      activator activity and accelerated the migration of BECs in a chemotactic
      fashion, which may contribute to the process of angiogenesis in vivo. These
      results suggest that GDF-5 is one of the molecules which induce angiogenesis in
      the bone formation process.

PMID- 9281372
TI  - Antibody cross-linking of the thymocyte-specific cell surface molecule CTX causes
      abnormal mitosis and multinucleation of tumor cells.
AB  - The thymocyte-specific cell surface molecule CTX is a developmentally regulated
      type I transmembrane protein of the immunoglobulin superfamily which, in the
      amphibian Xenopus, is exclusively expressed by a large fraction of cortical
      thymocytes and by different cell lines derived from independent spontaneous
      thymic tumors. Antibody cross-linking of CTX in vitro inhibits the growth of
      tumor cells and causes morphological alterations. Cells divide abnormally,
      accumulate in the G2/M phase of the cell cycle, and become multinucleated. This
      demonstrates, for the first time, that multinucleation can be induced by
      specifically cross-linking a cell surface molecule.

PMID- 9281370
TI  - Antiapoptotic action of 1,25-dihydroxyvitamin D3 is associated with increased
      mitochondrial MCL-1 and RAF-1 proteins and reduced release of cytochrome c.
AB  - Release of mitochondrial cytochrome c has been recently linked to the activation
      of the "executioner" phase of the cellular programs for death by apoptosis. This
      release is known to be negatively regulated by Bcl-2 and Bcl-XL proteins. We show
      here that treatment of human leukemia cells HL60 with 1,25-dihydroxyvitamin D3
      (1,25D3) results in progressive increases in the levels of cellular antiapoptotic
      protein Mcl-1, a transient increase in Al protein level, but no increases in Bcl
      2 or Bcl-XL proteins. The increase in Mcl-1 protein levels correlates with a
      reduced extent of apoptotic cell death induced by etoposide or the calcium
      ionophore A23187. The Mcl-1 protein is primarily localized in the mitochondria,
      and etoposide- or A23187-induced cytochrome c release is reduced in cells in
      which the mitochondria contain the Mcl-1 protein demonstrable by immunoblots. Raf
      1 protein can also be detected in the mitochondrial fractions that contain Mcl-1
      protein but not in the Mcl-1-negative fractions. These findings suggest that in
      these promyelocytic leukemia cells Mcl-1 has a function analogous to that of Bcl
      2 in other cells, i.e., to target Raf-1 to mitochondria and to reduce cell damage
      induced release of mitochondrial cytochrome c. Our findings provide a potential
      mechanism for the antiapoptotic action of 1,25D3 and show that differentiation
      and apoptosis signaling pathways not only interact but involve a proliferation
      associated gene, Raf-1.

PMID- 9281373
TI  - Nitric oxide and cGMP regulate endothelial permeability and F-actin distribution
      in hydrogen peroxide-treated endothelial cells.
AB  - We have previously reported that hydrogen peroxide (H2O2) has a concentration
      dependent effect on endothelial permeability and F-actin distribution. In the
      present study, we considered the involvement of endogenous production of nitric
      oxide (NO) in the indicated effect of H2O2. This was done by measuring
      endothelial permeability to sodium fluorescein (MW 376 Da, Na-F) and to different
      sized fluorescein-isothiocynate-labeled dextrans (FITC-dextrans) and by staining
      F-actin with rhodamine-labeled phalloidin in cultured bovine aortic endothelial
      cells growing on filters. A low concentration of H2O2 (10(-5) M) had no effect on
      either dense peripheral bands of F-actin (DPBs) or permeability. When N-nitro-l
      arginine methylester (l-NAME), an inhibitor of NO production, was coadministrated
      with 10(-5) M H2O2, DPBs were disrupted and the permeability to FITC-dextran 40
      and FITC-dextran 70, but not to Na-F and FITC-dextran 20, was increased.
      Combining of 10(-5) M H2O2 with l-arginine, a substrate for nitric oxide
      synthase, caused an increase in DPBs and a decrease in permeability to FITC
      dextran 40 and FITC-dextran 70. l-arginine or l-NAME alone had no effect on
      either F-actin structure or endothelial permeability. A 10-fold higher
      concentration of H2O2 caused a disruption of DPBs and an increase in
      permeability; this could be prevented by adding l-arginine. An analogue of cGMP,
      i.e., 8-Br-cGMP, maintained DPBs and abolished the increase in permeability
      induced by the treatment with either 10(-4) M H2O2 or a combination of H2O2 and l
      NAME. These results suggest that the endogenous production of NO is involved in
      maintaining endothelial junctions in H2O2-treated cells and that this involvement
      occurs via a cGMP-dependent mechanism.

PMID- 9281374
TI  - Genomic instability and telomerase activity in human bronchial epithelial cells
      during immortalization by human papillomavirus-16 E6 and E7 genes.
AB  - Human papilloma virus types 16 and 18 contribute to the development of cervical
      carcinomas in which the E6 and E7 genes are frequently retained and expressed in
      the tumors. Our study explored the ability of the E6 and/or E7 genes to
      immortalize normal human bronchial epithelial (NHBE) cells and to reactivate
      telomerase expression in these cells. We have introduced the human papillomavirus
      type 16 E6 or E7 genes alone or in combination (E6/E7) into NHBE cells using the
      retroviral construct pLXSN. Cells expressing either the E6 or the E7 oncoproteins
      alone displayed an increased colony-forming efficiency and a slightly extended in
      vitro life span before entering a crisis, from which immortalized cell lines were
      not obtained. Telomerase activity was not detected in cells expressing either E6
      or E7 individually. Cells expressing the E6/E7 oncoproteins in combination had a
      substantially increased life span before entering crisis. A subpopulation of
      these cells escaped from crisis and achieved 130 population doublings, suggesting
      immortalization. Telomerase activity was detected in these postcrisis cells, but
      was not detected prior to crisis. In addition, karyotypic analysis showed
      evidence of genomic instability in mass cultures as well as clones expressing E6,
      E7, or E6/E7. Abnormalities included numerous monosomies and trisomies, chromatid
      gaps and breaks, double minutes, and aberrant chromosomes. These results
      demonstrate that expression of E6 and/or E7 is sufficient to induce genomic
      instability and an extended life span to NHBE cells, but the presence of both E6
      and E7, along with at least one additional genetic or epigenetic event achieved
      during crisis, was required for reactivation of telomerase and the
      immortalization in this human cell type.

PMID- 9281375
TI  - A central segment of the NG2 proteoglycan is critical for the ability of glioma
      cells to bind and migrate toward type VI collagen.
AB  - Previous studies have established that the NG2 proteoglycan binds directly to
      type VI collagen. To further our understanding of the biochemical and functional
      significance of this interaction we have used NG2 cDNA to construct a series of
      NG2 mutants with deletions spaced throughout the entire length of the 260-kDa NG2
      core protein. Following transfection of these mutant cDNAs into B28 glioma cells,
      we determined the ability of mutant NG2 molecules to anchor type VI collagen on
      the cell surface. Eight of 11 transfectant populations were able to anchor type
      VI collagen. The three NG2 variants incapable of anchoring type VI collagen have
      deletions clustered within the central one-third of the NG2 ectodomain. These
      deletions identify a 469-amino-acid domain of NG2 responsible for binding of type
      VI collagen. Functional consequences of the NG2-type VI collagen interaction were
      explored by testing the relative ability of NG2-transfected and untransfected
      glioma cells to migrate toward type VI collagen. NG2-expressing cells exhibited a
      greater migratory response toward type VI collagen than their NG2-negative
      counterparts. This enhanced migration could be specifically inhibited with NG2
      antibodies. Furthermore, glioma cells expressing NG2 in which the collagen
      binding domain was deleted failed to exhibit this enhanced migration, whereas NG2
      mutants in which non-collagen-binding regions were deleted continued to exhibit
      increased chemotaxis toward the type VI collagen. These comparisons confirm the
      importance of the central collagen-binding domain in mediating functionally
      important interactions between NG2 and type VI collagen.

PMID- 9281376
TI  - Nuclear accumulation of the U1 snRNP-specific protein C is due to diffusion and
      retention in the nucleus.
AB  - The U1 small nuclear ribonucleoprotein particle (snRNP) has an important function
      in the early formation of the spliceosome, the multicomponent complex in which
      pre-mRNA splicing takes place. The nuclear localization signals of two of the
      three U1 snRNP-specific proteins, U1-70K and U1A, have been mapped. Both proteins
      are transported actively to the nucleus. Here we show by microinjection of
      Xenopus laevis oocytes that the third U1 snRNP-specific protein, U1C, passively
      enters the nucleus. Furthermore, we show that in both X. laevis oocytes and
      cultured HeLa cells mutant U1C proteins that are not able to bind to the U1 snRNP
      do not accumulate in the nucleus, indicating that nuclear accumulation of U1C is
      due to incorporation of the protein into the U1 snRNP.

PMID- 9281378
TI  - Effect of the insulin-like growth factor I receptor on ionizing radiation-induced
      cell death in mouse embryo fibroblasts.
AB  - We have investigated the effect of the insulin-like growth factor I receptor (IGF
      IR) on ionizing radiation (IR)-induced cell death using the following two mouse
      embryo fibroblast cell lines: (i) R- cells with a null mutation of the IGF-IR
      gene, therefore expressing no endogenous IGF-IR; (ii) R+ cells derived from R-
      cells, a stable transfectant overexpressing the human IGF-IR. Numbers of R- cells
      began to detach from dishes and float into the medium about 48 h after 10 Gy of X
      irradiation. Internucleosomal DNA fragmentation detected by agarose gel
      electrophoresis, which is characteristic of apoptosis, was observed in the
      floating R- cells, but not in the attached cells. Unexpectedly, morphological
      analysis of the floating cells 72 h after irradiation revealed that only about
      half of them showed apoptotic death and the rest showed a nonapoptotic,
      presumably necrotic, one. On the other hand, R+ cells retained more than 90%
      viability even 4 days after irradiation, and very few floating cells were
      observed. The G2 arrest was induced in both cell lines following irradiation and
      G2/M fractions similarly returned to normal levels by around 20 h after
      irradiation, indicating that the cell death which appeared thereafter in R- cells
      is mediated through mitosis. Significant induction of p53 following irradiation
      was not detected by Western blot analysis in either R- or R+ cells. Collectively,
      these results demonstrate that signal transduction pathways originating from the
      IGF-IR may be involved in preventing IR-induced apoptosis and necrosis without
      affecting cell cycle arrest or p53 pathways.

PMID- 9281377
TI  - The alpha7beta1 integrin mediates adhesion and migration of skeletal myoblasts on
      laminin.
AB  - Many aspects of myogenesis are believed to be regulated by myoblast interactions
      with specific components of the extracellular matrix. For example, laminin has
      been found to promote adhesion, migration, and proliferation of mammalian
      myoblasts. Based on affinity chromatography, the alpha7beta1 integrin has been
      presumed to be the major receptor mediating myoblast interactions with laminin.
      We have prepared a monoclonal antibody, O26, that specifically reacts with both
      the X1 and the X2 extracellular splice variants of the alpha7 integrin chain.
      This antibody completely and selectively blocks adhesion and migration of rat
      L8E63 myoblasts on laminin-1, but not on fibronectin. In contrast, a polyclonal
      antibody to the fibronectin receptor, alpha5beta1 integrin, blocks myoblast
      adhesion on fibronectin, but not on laminin-1. The alpha7beta1 integrin also
      binds to a mixture of laminin-2 and laminin-4, the major laminin isoforms in
      developing and adult skeletal muscle, but O26 is a much less potent inhibitor of
      myoblast adhesion on the laminin-2/4 mixture than on laminin-1. Based on affinity
      chromatography, we suggest that this may be due to higher affinity binding of
      alpha7X1 to laminin-2/4 than to laminin-1.

PMID- 9281379
TI  - Changes in actin filament organization during pseudopod formation.
AB  - Fluorescent phalloidin has been introduced into Dicytostelium amoebae in order to
      visualize dynamic changes in the localization of F-actin during pseudopod
      extension. Phalloidin was initially localized to the peripheral cortex of the
      cell. Newly formed pseudopods were not fluorescent, indicating that phalloidin
      was tightly bound to existing F-actin filaments and could not rapidly relocalize
      to newly formed filaments. As pseudopod extension proceeded, the fluorescent
      signal disappeared from the region directly underlying the expansion zone,
      leaving a gap in the actin cortex. Similar results were obtained in both wild
      type cells and those lacking myosin II heavy chain. The disappearance of the
      fluorescent signal from the cortical region underlying the new pseudopod is
      presumed to be due to breakdown of the actin cortex and dispersion of the
      remnants. These results suggest that new pseudopods are not built upon the
      existing actin cortex but rather that the cortex is locally solated as part of
      the construction of the new actin network.

PMID- 9281380
TI  - Sequence determinants for hnRNP I protein nuclear localization.
AB  - hnRNP I, also referred to as polypyrimidine tract binding protein, is one of the
      proteins associated with nascent pre-mRNA in the heterogeneous nuclear
      ribonucleoprotein (hnRNP) complexes. As for all karyophilic proteins, the nuclear
      import of hnRNP proteins requires specific sequence determinants that in many
      instances differ from the canonical import signal. In order to identify the
      sequences responsible for the nuclear localization, various hnRNP I portions were
      fused to a reporter protein (bacterial chloramphenicol acetyl transferase) and
      used in transient transfection assay. By this approach we identified a 60-amino
      acid sequence located at the amino terminus of hnRNP I (designated NLD-I) that is
      both necessary and sufficient for nuclear localization. NLD-I represents a novel
      bipartite type of nuclear localization signal that bears no resemblance to other
      nuclear localization determinants so far identified in hnRNP proteins.

PMID- 9281381
TI  - Epidemiology and estimated population burden of selected autoimmune diseases in
      the United States.
AB  - Autoimmune diseases cause significant and chronic morbidity and disability. The
      actual number of persons in the United States that are affected by autoimmune
      diseases and the resultant magnitude of their impact on the public's health are
      limited to a few specific diseases. In order to understand the clinical, public
      health and economic importance of these diseases it is necessary to have
      estimates of incidence and prevalence rates in the population. In this analysis,
      we estimate the number of persons affected by 24 autoimmune diseases in the
      United States by applying mean weighted prevalence and incidence rates obtained
      from published articles to U. S. Census data. The study was restricted to 24
      autoimmune predefined diseases for which there was direct or indirect evidence
      for autoimmune pathogenesis. Subsequently, we used computerized search software
      and ancestry searching (bibliographies) to conduct a comprehensive search of
      articles published from 1965 to the present. Eligible studies included those
      which adhered to standard disease definitions and which included population-based
      estimates of incidence or prevalence rates. Mean weighted incidence and
      prevalence rates were calculated from eligible published studies with greater
      weight proportionately given to larger studies. The mean rates were then applied
      to the U.S. Census population figures to estimate the number of persons currently
      afflicted with each disease and the number of new cases occurring each year in
      the United States. Only U.S. and European studies were used to estimate
      prevalence and incidence rates when there were at least six eligible studies
      available for a disease. When there were fewer than six studies, all available
      studies were included, regardless of country of origin. The number of eligible
      incidence and prevalence studies found in the literature varied considerably
      between the 24 autoimmune diseases selected. The largest number of eligible
      prevalence studies were conducted on multiple sclerosis (MS), rheumatoid
      arthritis, and systemic lupus erythematosus (SLE) (>/=23), followed by insulin
      dependent diabetes (IDDM), myasthenia gravis, primary biliary cirrhosis, and
      scleroderma (>/=7). There were only one to four eligible studies done on 11 other
      diseases, and no prevalence studies on 6 diseases. Incidence studies were less
      frequent but the largest number of studies were conducted on IDDM (n = 37) and MS
      (n = 28), followed by Graves' disease/hyperthyroidism, glomerulonephritis,
      primary biliary cirrhosis, rheumatic fever, rheumatoid arthritis, scleroderma,
      and SLE (>/=9). On the other 11 diseases, there were one to six eligible studies,
      and no studies on 5 diseases. There were no eligible incidence or prevalence
      studies on Goodpasture's syndrome, idiopathic thrombocytopenia purpura, or
      relapsing polychondritis. Overall we estimate that 8,511,845 persons in the
      United States or approximately 1 in 31 Americans are currently afflicted with one
      of these autoimmune diseases. The diseases with the highest prevalence rates were
      Graves'/hyperthyroidism, IDDM, pernicious anemia, rheumatoid arthritis,
      thyroiditis, and vitiligo, comprising an estimated 7,939, 280 people or 93% of
      the total number estimated. Glomerulonephritis, MS, and SLE added an estimated
      323,232 people. The prevalence of the other diseases reviewed were rare, less
      than 5.14/100,000. Most diseases were more common in women. From the incidence
      data we estimate that 237,203 Americans will develop an autoimmune disease in
      1996 and that approximately 1,186,015 new cases of these autoimmune diseases
      occur in the United States every 5 years. Women were at 2.7 times greater risk
      than men to acquire an autoimmune disease. After reviewing the medical literature
      for incidence and prevalence rates of 24 autoimmune diseases, we conclude that
      many autoimmune diseases are infrequently studied by epidemiologists. As a result
      the total burden of disease may be an underestimate. (ABSTRACT TRUNCATED)

PMID- 9281382
TI  - TGF-beta: a critical modulator of immune cell function.

PMID- 9281383
TI  - 131I dose-dependent thyroid autoimmune disorders in children living around
      Chernobyl.
AB  - We assessed the major lymphocyte subsets in the peripheral blood, thyroid
      ultrasonography, levels of serum autoantibodies to thyroglobulin (AbTg), thyroid
      hormones, and thyroid-stimulating hormone (TSH) in 53 children without any
      chronic diseases living continuously around Chernobyl. The subjects ranged in age
      from 7 to 14 years and had different doses of 131I to their thyroid. Healthy
      children living on noncontaminated areas were assessed as controls. The majority
      of children with doses of 131I had normal levels of thyroid hormones. However,
      the percentages of positive sera for AbTg, TSH levels, ultrasonographic thyroid
      abnormalities, and abnormal echogenicity were significantly higher in children
      with doses of 131I than in controls. The dose of 131I to thyroid correlated
      positively with serum AbTg levels, percentage of CD3+CD4+ cells, and
      CD3+CD4+/CD3+CD8+ cell ratio and negatively with number of CD3+CD8+ and CD3
      /CD16, CD56+ cells. Thus, our study demonstrates an association between dose of
      131I and autoimmune thyroid disorders in this population of children.

PMID- 9281385
TI  - Natural killer cells in the late decades of human life.
AB  - We examined the lymphocyte subsets and indices of natural killer (NK) cell
      activity (lytic unit (LU), index of absolute NK cell activity in vivo (ALU), and
      NK cell activity on a per-cell basis (PCNK)) in 82 people (age, 30-99 years) who
      were immunologically normal. Although the number of NK cells was maintained
      throughout the examined age range, the ALU and PCNK values correlated negatively
      with age. We then examined whether any of the various immunologic parameters,
      including the function and cell counts of NK cells, T cells, and neutrophils,
      related to past infectious episodes and death in the follow-up period in 44
      elderly subjects (age, 63-98 years). Only low ALU and PCNK values correlated with
      a past history of severe infection, while low LU, ALU, and PCNK values were the
      only parameters which correlated with death due to infection during the follow-up
      period. We propose that human NK cells do not escape the aging process and that a
      low NK cell function relates to the development of severe infections, which may
      be fatal, in elderly subjects.

PMID- 9281384
TI  - Cytokine mRNA expression in the B/W mouse model of systemic lupus erythematosus-
      analyses of strain, gender, and age effects.
AB  - To gain a better understanding of inherent gender-related effects on
      autoimmunity, cytokine genes were examined in female and male New Zealand Black X
      New Zealand White (B/W) mice, which are a murine model of systemic lupus
      erythematosus (SLE). In preliminary studies, semiquantitative reverse
      transcriptase-polymerase chain reaction analysis showed a trend for B/W spleen
      cell interferon gamma (IFN-gamma) mRNA in B/W female spleen cells to exceed that
      of males. This difference was obliterated following concanavalin A (Con A)
      stimulation. Spleen cells from B/W mice of both sexes were then examined at 6,
      18, and 27 weeks of age, and results were compared with matched groups of
      nonautoimmune DBA/2 mice. Pooled splenocytes from all 12 groups of animals were
      compared simultaneously for expression of mRNA specific for IFN-gamma,
      interleukin 4 (IL-4) and interleukin 6 (IL-6). Strain was a potent influence on
      cytokine transcripts. In unstimulated splenocytes from female and male B/W mice,
      there was a notable trend for IFN-gamma and IL-6 mRNA expression to exceed
      transcripts from nonautoimmune DBA/2 mice. When comparisons were carried out by
      gender, a highly significant increase of IFN-gamma transcripts was apparent in
      B/W females compared to B/W males at the age of 27 weeks. Following Con A
      incubation, strain and gender differences were eliminated. IL-4 transcript
      expression was similar in all pools of cells, and age was not an important factor
      in expression of any transcript. This study represents the first examination of
      multiple cytokine transcripts in lymphoid cells from B/W mice. In this hormone
      sensitive model of SLE, strain and gender determined in vivo expression of IFN
      gamma and IL-6 mRNA.

PMID- 9281387
TI  - Cytotoxicity of murine B lymphocytes induced by human VH4-34 (VH4.21) gene
      encoded monoclonal antibodies.
AB  - We have previously described specific binding and cytotoxicity of human B
      lymphocytes by VH4-34 gene-derived anti-i cold agglutinin (CA) mAbs. Here we
      demonstrate that the carbohydrate ligand recognized by human VH4-34 anti-i CA
      mAbs is also expressed on murine B lymphocytes. Similar to human B cells, binding
      of murine B lymphocytes by VH4-34-derived anti-i CA mAbs leads to rapid
      cytotoxicity of target cells as tested both in vitro and in vivo. Moreover, the
      mechanism leading to murine B cell death is also similar to human B cells, since
      morphologically identical membrane pores were detected within 15 min of mAb
      exposure by scanning electron microscopy. The conservation of the carbohydrate
      ligand across species provides an ideal system to study the function of human VH4
      34 gene derived Abs in immune regulation.

PMID- 9281386
TI  - Umbilical cord blood lacks circulating B lymphocytes expressing surface IgG or
      IgA.
AB  - In vitro umbilical cord blood B lymphocytes fail to form IgG and IgA secreting
      plasma cells when stimulated with Pokeweed mitogen. Since previous investigators
      have found percentages of B lymphocytes expressing surface IgG or surface IgA
      comparable to those seen in adults, this implies a defect in umbilical cord blood
      B-lymphocyte function. We have examined surface Ig expression on umbilical cord
      blood B lymphocytes by flow cytometry under conditions in which serum derived Ig
      are rigorously excluded. Under these conditions no B lymphocytes expressing
      surface IgG or IgA, which should serve as precursors for IgG and IgA secreting
      plasma cells, were observed. This finding was confirmed by comparing the ratio of
      mRNA levels for immunoglobulin gamma-chain to mu-chain in mononuclear cells by
      quantitative mRNA-based PCR. The ratio in umbilical cord mononuclear cells was 10
      fold less than that seen in adult cells. The inability of newborn peripheral
      blood to form IgG and IgA plasma cells may result from an absence of appropriate
      precursor cells and not a defect in B lymphocyte maturation.

PMID- 9281388
TI  - Differential influences of gold sodium thiomalate and bucillamine on the
      generation of CD14+ monocyte-lineage cells from bone marrow of rheumatoid
      arthritis patients.
AB  - An adequate supply of peripheral blood monocytes, granulocytes, and platelets is
      necessary for an optimal inflammatory process. We have previously demonstrated
      that the generation of CD14(+) monocyte-lineage cells from the bone marrow is
      accelerated in patients with rheumatoid arthritis (RA). The current studies
      examined the influences of gold sodium thiomalate (GST) and bucillamine (BUC),
      two potent disease-modifying antirheumatic drugs (DMARDs), on the capacity of
      bone marrow progenitor cells to generate CD14(+) cells in patients with RA, in
      order to delineate their mechanisms of action. CD14(-) cells purified from bone
      marrow specimens of 13 patients with active RA who were not taking DMARDs were
      cultured in the presence or absence of pharmacologically attainable
      concentrations of GST (25 microM) or intramolecular disulfide form of bucillamine
      (BUC-ID, 3 microM), a major metabolite of BUC. After incubation for 14 days, the
      cells were analyzed by flow cytometry for expression of CD14, HLA-DR, and CD54.
      The generation of CD14(+) cells from RA bone marrow CD14(-) progenitor cells was
      significantly suppressed by GST, but not by BUC-ID. The expression of HLA-DR on
      the bone marrow-derived CD14(+) cells was also significantly inhibited by GST,
      but not by BUC-ID. Of note, neither GST nor BUC-ID influenced the expression of
      CD54 on the bone marrow-derived CD14(+) cells, indicating that the expression of
      HLA-DR and CD54 on the bone marrow-derived CD14(+) cells is regulated by
      different mechanisms. The results are consistent with the hypothesis that one of
      the effects of DMARDs may involve the interference with monocyte differentiation
      in the bone marrow. Moreover, the data emphasize that in contrast with BUC, GST
      is a potent inhibitor of monopoiesis in RA patients.

PMID- 9281389
TI  - Immunoregulatory changes in Kawasaki disease.
AB  - Kawasaki disease (KD) is an acute vasculitis of unknown etiology, occurring in
      young children and treated with intravenous gamma globulin (IVIG) to prevent
      significant cardiac morbidity and mortality. We studied KD patients pre- and post
      IVIG therapy and at >40 days posttherapy, additionally comparing them with
      matched pediatric control patients and parents. Using three-color flow cytometry,
      we examined immune changes in KD, especially previously unassessed markers of T
      lymphocyte activation, memory, and adhesion. The percentage of cells positive for
      CD19, CD25, CD38, and CD71 was significantly lower during convalescence compared
      with pre-IVIG (medians: CD19, 18% vs 26%, P = 0.0004; CD25, 6% vs 9% for CD3(+)
      cells, P = 0.0074; CD38, 78% vs 89% for CD8(+) cells, P = 0.0015; CD71, 1% vs 6%
      for CD4(+) cells, P = 0.0024). The proportion of CD3(+) cells increased (medians:
      CD3, 66% vs 45%, P < 0.0001). Values for all parameters varied greatly pre- and
      post-IVIG, but not in a consistent direction. The sole patient with cardiac
      abnormalities had the greatest pre-/post-IVIG variability. These changes support
      the involvement of T-lymphocytes in the acute KD vasculitic process. They also
      suggest that T-lymphocytes involved in endothelial damage during acute KD may be
      subsequently removed or eliminated from the peripheral blood.

PMID- 9281390
TI  - Analysis of the molecular basis of synovial rheumatoid factors in rheumatoid
      arthritis.
AB  - The objective of this study was to better understand the molecular basis of IgM
      rheumatoid factor in rheumatoid arthritis (RA). We recently generated 10
      different monoclonal IgM RF (mRF) molecules isolated from the synovium of a
      single patient with RA. The heavy (H) and light chain (L) variable region (V)
      genes of these 10 mRFs were cloned and sequenced. Six mRFs used kappa light
      chains and 4 mRFs used lambda light chains. Of particular interest, 8 of 10 heavy
      chains used the JH4 joining region gene, and all five VH4 heavy chains used the
      DK4 diversity region gene with the JH4. Four of the VH4 clones used the same
      germline gene, likely representing a novel but closely related germline gene to
      VH4.18, and may be clonally related because of the extensive homology in their
      heavy chain sequence. Two VH4 clones shared the same light chain gene, VkappaIIIb
      kv325 (99% homology) and the same JK4 joining region gene, while three VH4 clones
      used two different light chain genes, an uncommon Vkappa4 and a Vlambda4 gene,
      respectively. In this RA patient, there was recurrent utilization of VH4-DK4
      21/10-JH4 genes and a recurring association with gene elements Vkappa3 and
      Vlambda4. Recurring usage of Vkappa3 (kv325) and Vlambda4 (lv418) gene elements
      may result from a light chain editing process whereby immature autoreactive B
      cells encountering self-antigen attempt, and often succeed, in altering their
      specificities through secondary Ig light chain gene rearrangement. Moreover, the
      oligoclonality of these RFs suggest clonal relatedness secondary to an antigen
      driven response.

PMID- 9281391
TI  - Autoantibody production and cytokine profiles of MHC class I (beta2
      microglobulin) gene deleted New Zealand black (NZB) mice.
AB  - We established a colony of MHC class I deleted (knockout) NZB mice, which lack
      the beta2 microglobulin gene (NZB.beta2m-/-), to characterize the contribution of
      MHC class I to the thymic microenvironment abnormalities, autoantibody production
      and lupus-like disease of NZB mice. Using an extensive panel of well
      characterized monoclonal antibodies defining thymic epithelial and other stromal
      elements, we demonstrated that deletion of MHC class I molecules does not change
      the thymic abnormalities, including the presence of a cortical epithelial cell
      free region, ectopic expression of medullary epithelial antigens, and the
      irregular shape of the medullary epithelial network of NZB mice. Moreover, the
      decreased staining of MTS 33(+) cells, a marker of premature thymocyte
      maturation, was also seen in NZB.beta2m-/-. However, although NZB.beta2m-/- mice
      had approximately the same levels of IgM and IgG anti-ss and dsDNA antibodies
      when compared to control NZB mice, there were significant alterations in the
      incidence and onset of anti-erythrocyte antibody levels. NZB.beta2m-/- had a
      lower incidence and a delayed onset of anti-erythrocyte autoantibody production
      compared to that seen in NZB mice. We also compared constitutive and PHA-P-driven
      levels of IFN-gamma, IL-4, IL-6, and IL-12 in cells from NZB, NZB.beta-/-2, and
      control C57BL/6 mice. Mitogen stimulated cells showed a decreased IFN-gamma, and
      a marked increase in IL-6 and IL-12 in NZB and NZB.beta2m-/- mice.

PMID- 9281392
TI  - Class II haplotype differentially regulates immune response in HgCl2-treated
      mice.
AB  - One of the most striking features of exposure to low doses of mercury in mice is
      the high-titer haplotype-linked anti-nucleolar (ANoA) autoantibody response. Mice
      of H-2(s) haplotype have been high responders, while H-2(b) mice have been low.
      This pattern has been attributed to the class II molecule itself, but the poor
      response of F1 crosses between high and low responders raised the possibility
      that the anti-fibrillarin specificity was actually due to a closely linked
      dominant negative gene. To test the role of class II explicitly, F1 crosses
      between congenic B6.SJL (H-2(s)) and C57BL/6 (H-2(b)) mice with a targeted
      deletion of I-AbAbeta were generated, creating mice heterozygous for all MHC
      loci, but expressing only I-As. In comparison with B6.SJL, no diminution of ANoA
      titers was found, proving that I-As itself was responsible for susceptibility and
      I-Ab for downregulation. Unlike I-A, expression of the I-E class II molecule
      could not downregulate the response in an otherwise susceptible mouse. These
      results suggest a complicated role for class II in the regulation of a novel,
      environmentally induced autoimmune response.

PMID- 9281393
TI  - Anti-MIP-1alpha and anti-RANTES antibodies: new allies of HIV-1?
AB  - The human immunodeficiency virus type 1 was recently found to use several
      chemokine receptors in addition to the CD4 molecule for attachment to, and fusion
      with, CD4+ cells. The interaction between macrophage-tropic HIV-1 strains and one
      of these chemokine receptors, CCR5, was shown to involve the V3-loop of the viral
      envelope glycoprotein gp120. Physiological ligands of CCR5, namely the beta
      chemokines MIP-1alpha, MIP-1beta, and RANTES, were found to competitively inhibit
      the V3-loop-CCR5 interaction. We therefore hypothesized that the V3-loop of gp120
      of macrophage-tropic HIV-1 may share a binding site on CCR5 with MIP-1alpha, MIP
      1beta, and RANTES and that the V3-loop therefore might have some homology with
      these beta-chemokines. In the present study, we could demonstrate that affinity
      purified anti-V3-loop antibodies isolated from serum of an HIV-1-infected patient
      bound to MIP-1alpha and RANTES. Furthermore, sera of HIV-infected hemophilia
      patients without AIDS or ARC had significantly higher anti-MIP-1alpha and anti
      RANTES antibody activities than sera of HIV-infected hemophilia patients with
      AIDS. We speculate that the higher activities of anti-MIP-1alpha and anti-RANTES
      antibodies in asymptomatic HIV-1 infected individuals might be due to a cross
      reaction of beta-chemokines with anti-V3-loop antibodies raised against gp120 of
      macrophage-tropic HIV-1 strains, known to be prevailing in the asymptomatic stage
      of HIV infection. Such anti-chemokine antibodies may play a deleterious role in
      the pathogenesis of AIDS by reducing the chemokines' potential to inhibit HIV-1
      entry into CD4+ cells.

PMID- 9281394
TI  - The Proteases of American Foulbrood Scales
AB  - The gross protease activity of pathological samples of American foulbrood
      infected cadavers from several UK sources was studied. In all cases the bulk of
      the activity is caused by neutral protease(s) (optimum pH ca. 6.8) that are
      inhibited by chelating agents such as EDTA and 1,10 phenanthroline (indicating
      metalloproteases) but not by inhibitors of other classes of proteolytic enzymes.
      The proteases, which derive from the infectious agent of AFB, Paenibacillus
      larvae, were unusual in being insensitive to phosphoramidon and in not degrading
      FAGLA, the artificial substrate specific for most Bacillus metalloproteases. The
      enzymes in AFB ropes and scales had temperature optima of 60-65&deg;C and were
      inactivated quickly on incubation at 80&deg;C. Activity at moderate temperatures
      (37&deg;C) was great on general substrates such as casein, gelatin, and hide
      powder azure, slight on elastin-Congo red, and nonexistent on collagen. In SDS
      polyacrylamide gels the enzymes from the various sources all had molecular
      weights about 24 kDa. The proteases could be detected only zymographically after
      brief washing to remove SDS. On silver-stained gels no bands corresponding to the
      enzymes' activities could be detected. On native polyacrylamide gels enzyme
      activity was resolved zymographically as at least three metalloprotease bands
      with samples from different sources showing a variety of patterns.

PMID- 9281395
TI  - Replication of a Gonad-Specific Insect Virus in TN-368 Cells in Culture
AB  - A newly discovered, nonoccluded, insect virus, known as gonad-specific virus
      (GSV) was found to replicate in Trichoplusia ni (TN-368) tissue culture cells.
      Light-microscope observations indicated that 90% of the infected cells showed
      cytopathic effects by 2 days postinoculation. Electron-microscopic observations
      revealed the productive replication of this nonoccluded virus with enveloped
      virus particles clearly visible in the nucleus of infected cells. These particles
      had approximately the same size and shape reported for GSV recovered from the in
      vivo host, Helicoverpa zea (corn earworm). Southern blot analysis indicated that
      the EcoRI restriction enzyme profiles of viral DNA from GSV-infected TN-368 were
      nearly identical to that of viral DNA from insects. Inoculation of healthy
      female, H. zea adults with cell-culture-derived virus yielded progeny moths with
      the same symptoms as insects inoculated with GSV propagated in vivo. These
      studies clearly demonstrate the ability of GSV to replicate in TN-368 cells in
      culture.

PMID- 9281396
TI  - Enzymes Involved in Defense Functions of Hemocytes of Mussel Mytilus
      galloprovincialis
AB  - Mytilus galloprovincialis hemocytes contain phosphatases, esterases, proteases,
      and glucosidases as revealed by a semiquantitative colorimetric method. The
      activity levels of some enzymes changed throughout the months of the experiment
      without a seasonal pattern. No differences in the enzyme levels were found
      between the two groups of mussels of different age (cultivated 11 and 19 months
      on ropes hung from the same raft). Light microscopy study of hemocyte enzymes
      showed that hyalinocytes and granulocytes had reaction of acid phosphatase, beta
      glucuronidase, alpha-naphthyl butyrate esterase, naphthol AS-D chloroacetate
      esterase, and alpha-naphthyl acetate esterase. Phenoloxidase and peroxidase
      activities were also detected in monolayers of hemocytes. Ultrastructural study
      revealed that the granules of hemocytes contained acid phosphatase, beta
      glucuronidase, nonspecific esterases, peroxidase, and NADH oxidase. Products of
      beta-glucuronidase and peroxidase reaction were also localized in the plasma
      membrane. Lysozyme activity level was higher in hemocytes than in serum.
      Comparison between the two groups of different age showed a higher activity level
      of lysozyme in younger mussels.

PMID- 9281397
TI  - Sugar Acquisition during the Development of Microsporidian (Microspora:
      Nosematidae) Spores
AB  - Helicoverpa zea larvae were infected with Vairimorpha necatrix. The fat body was
      triturated and sporulation stages were fractionated according to buoyant density
      by Ludox density gradient centrifugation. Spores and sporulation stages formed
      two minor bands with buoyant densities of 1.072 and 1.121 g/ml, and two major
      bands with buoyant densities of 1.150 and 1.198 g/ml. The higher bands of less
      dense sporoblastic stages first appeared 96 hr following infection and the band
      containing the heaviest (1.198 g/ml) and most refringent mature spores appeared
      last, ca. 24 hr after the appearance of the other bands. Although the bands
      remained in the same relative positions regardless of the time after inoculation,
      the percentage of spores in Band 4 increased with time. The concentration of
      sugar in the spores from the 1.198-g/ml band was more than four times the
      concentration found in spores in the 1.150-g/ml band and accounted for more than
      60% of the increase in spore weight between the two density classes. Similar
      tests with Nosema algerae yielded similar results, with sugars accounting for 88%
      of the increased spore weight. Sugar acquisition appears to occur during the
      attainment of the final spore density and perhaps signals spore maturation.

PMID- 9281398
TI  - Suitability of 30 Agricultural Products and By-Products as Nutrient Sources for
      Laboratory Production of Bacillus thuringiensis subsp. aizawai (HD133)
AB  - Bacillus thuringiensis subsp. aizawai (HD133) was grown in culture media in which
      dextrose was a common carbon source and 30 different agricultural products and by
      products were tested as the main nitrogen sources. These products included
      legumes, cereals, animal proteins, leaf proteins, yeasts, oilseeds, tubers, and
      casamino acid. Of the 30 products tested, cottonseed meal, defatted soy flour,
      and corn gluten meal were the most efficient substrates for the production of
      spore-crystal biomass and endotoxin potency. The carbohydrate/nitrogen ratios for
      these additives ranged from 0.3 to 0.5 and the glutamic acid content of their
      proteins from 9.2 to 16.0%. There was no close relationship between the estimates
      of the amounts of endotoxin produced and the potency of the product when fed to
      bertha armyworm, Mamestra configurata.

PMID- 9281400
TI  - The Effect of Pathogen Dosage on the Pathogenicity of Neozygites floridana
      (Zygomycetes: Entomophthorales) to Mononychellus tanajoa (Acari: Tetranychidae)
AB  - How the pathogen inoculum size affects the pathogenicity of Neozygites floridana
      to Mononychellus tanajoa was studied at 28&deg;C, 12L:12D photoperiod and 90-100%
      RH. All inoculum sizes tested (one, two, four, six, and eight capilliconidia per
      mite) were lethal. Dead mites started to appear 48 hr after exposure to the
      conidia. Inoculum size significantly affected time to mortality. All mites
      exposed to six or eight capilliconidia died of mycosis 57.1 and 62.9 hr,
      respectively, after infection. At smaller doses, infection rates were lower, dead
      mites started to appear later, and time to mortality was significantly longer
      (between 68.7 and 89.4 hr). Most mites died within the first 6 hr of the dark
      phases of the photoperiod.

PMID- 9281399
TI  - A nuclear polyhedrosis virus from the obliquebanded leafroller, Choristoneura
      rosaceana (Harris) (Lepidoptera:Tortricidae).
AB  - A nuclear polyhedrosis virus (CrMNPV) has been isolated from larvae of the
      obliquebanded leafroller Choristoneura rosaceana (Harris) collected near St.
      Quentin in northwest New Brunswick, Canada. Restriction endonuclease digestion
      gel electrophoresis of this virus, using a number of different endonucleases and
      whole CrMNPV genome Southern hybridization, have shown it to be different but
      similar to the equivalent virus from the spruce budworm Choristoneura fumiferana
      (Clem.) (CfMNPV). The polyhedrin gene of CrMNPV has been isolated, cloned, and
      sequenced and shown to have a predicted amino acid sequence only two amino acids
      different from the CfMNPV polyhedrin. In bioassays against spruce budworm larvae,
      CrMNPV had little pathogenicity to that host.

PMID- 9281402
TI  - Bacillus thuringiensis delta-Endotoxin Binding Sites in Two Lepidoptera, Wiseana
      spp. and Epiphyas postvittana
AB  - Proteins from the midguts of the light-brown apple moth Epiphyas postvittana
      (Walker) and the porina caterpillars Wiseana cervinata (Walker), W. copularis
      (Meyrick), and W. jocosa (Meyrick) which bind the Bacillus thuringiensis delta
      endotoxin Cry1Ba were characterized using Cry1Ba labeled with Bolton and Hunter
      reagent. A comparison of two iodine labeling techniques on the toxicity of B.
      thuringiensis delta-endotoxins showed that labeling using chloramine-T
      substantially decreased Cry1Ba toxicity against the light-brown apple moth E.
      postvittana, whereas labeling using the Bolton and Hunter reagent had no effect
      on the toxicity of either Cry1Ac or Cry1Ba to this insect. The characteristics of
      Cry1Ac binding sites from E. postvittana midguts were determined by competitive
      binding assays using toxin labeled with 125I by both methods. The difference in
      values of binding site characteristics found by the two methods was shown to be
      caused by modification of the toxin by the conditions of chloramine-T labeling.
      The relationship between number and affinity of the binding sites and the
      toxicity of the delta-endotoxins is discussed.

PMID- 9281401
TI  - Evaluation of the fungus Beauveria bassiana as a potential biological control
      agent against phlebotomine sand flies in Colombian coffee plantations.
AB  - In Colombia, the entomopathogenic fungus Beauveria bassiana (Deuteromycotina:
      Hyphomycetes) is widely used to control the coffee berry borer Hypothenemus
      hampei (Coleoptera: Scolytidae) in coffee plantations. Recent studies suggested
      that this fungus is also pathogenic to several important vectors of disease,
      including Phlebotomus papatasi and Lutzomyia longipalpis (Diptera: Psychodidae).
      The present study evaluated the use of B. bassiana as a potential biological
      control agent against phlebotomine sand flies in Colombian coffee plantations.
      Histopathologic examination indicates that B. bassiana is unable to infect sand
      flies under natural conditions, although dead sand flies were shown to be readily
      infected. In addition, laboratory bioassays where flies were exposed to the
      fungus applied onto coffee plants (though not filter paper) showed lower mean
      survival times than the control.

PMID- 9281404
TI  - Presence and Histopathological Effects of the Copepod Pseudomyicola spinosus in
      Mytilus galloprovincialis and Mytilus californianus
AB  - The copepod Pseudomyicola spinosus (Cyclopoidea, Myicolidae) was found in the
      mantle, gills, intestine, stomach, and connective tissue of the digestive gland
      of the blue mussel Mytilus galloprovincialis and the California mussel Mytilus
      californianus from Baja California, northwestern Mexico. The copepod can move
      from the mantle and gills to the digestive gland and vice versa. In M.
      galloprovincialis, copepod prevalence was 93% and its number ranged from 0 to 20
      (mean, 5) in the mantle and gills and from 0 to 5 (mean, 1.1) in the digestive
      gland. In M. californianus, copepod prevalence was 43% and its number ranged from
      0 to 2 (mean, 0.4) in the mantle and gills and from 0 to 1 (mean, 0.1) in the
      digestive gland. In the epithelium of the stomach and intestine of both mussel
      species studied, the appendages of P. spinosus may produce a loss of epithelial
      cells. Occasionally there was a light increase of hemocytes at the basal region
      of the stomach and intestinal epithelia where copepod was attached. In the lumen
      of the stomach and intestine copepods may be surrounded by mucus. P. spinosus was
      also found among the connective tissue of the digestive gland, apparently as a
      result of penetration through the wall of the stomach or other digestive organs.
      A granuloma-like structure engulfing the copepod in the connective tissue of the
      digestive gland was found. This is the first description of histopathological
      effects of P. spinosus in mussels.

PMID- 9281403
TI  - Infection of the gonads of the SimES strain of Drosophila simulans by the
      hereditary reovirus DSV.
AB  - The S character of Drosophila simulans SimES-st strain undergoes a non-mendelian
      transmission. It has been postulated that a virus, Drosophila S virus (DSV),
      could be the causative agent. Electron microscopy analysis of gonads of flies
      showing a strong S phenotype revealed the presence of virus in or near the germ
      cells. The S character transmission rate is greater in females than that in
      males. Similarly, the level of infection by DSV is higher in ovaries than that in
      testes. Flies treated at a nonpermissive temperature do not present the S
      phenotype and appear to be cured from the virus. This information, taken together
      with previous work, makes the hypothesis that DSV is the causative agent of the S
      phenotype more than likely.

PMID- 9281405
TI  - Ultrastructures of Nosema typographi Weiser 1955 (Microspora: Nosematidae) of the
      Bark Beetle Ips typographus L. (Coleoptera; Scolytidae)

PMID- 9281406
TI  - Avoidance of Encapsulation by Heterorhabditis spp. Infecting Larvae of Tipula
      oleracea

PMID- 9281407
TI  - Ingestion Time Does Not Influence the Susceptibility of Trichoplusia ni to a
      Nuclear Polyhedrosis Virus

PMID- 9281408
TI  - Virus-like Particles Detected from Juvenile Abalones (Nordotis discus discus)
      Reared with an Epizootic Fatal Wasting Disease

PMID- 9281409
TI  - Urinary inhibitors of polymerase chain reaction and ligase chain reaction and
      testing of multiple specimens may contribute to lower assay sensitivities for
      diagnosing Chlamydia trachomatis infected women.
AB  - In a comparison of commercial ligase chain reaction (LCR; Abbott) and polymerase
      chain reaction (PCR; Roche) assays, measuring plasmid genes of Chlamydia
      trachomatis, some specimens were found to be negative by either or both assays
      but positive in traditional culture or antigen detection tests. Of 767 women, 35
      were found to be infected by cervical or urine testing. Twenty three specimens
      from 16 women may have contained inhibitors in six cervical swabs (CS) and 15
      first void urines (FVU). By performing dilution and 'spiking' experiments on five
      FVU, inhibitors of PCR, LCR or both, which disappeared by dilution, were
      demonstrated. Confirmatory assays were used which amplified segments of the major
      outer membrane gene by PCR or LCR. When comparisons of assays were made on a
      single specimen type, the sensitivities of the amplification assays, compared to
      an expanded reference standard, were as follows: on CS, PCR was 93.8% (30/32) and
      LCR was 96.9% (31/32); on FVU, PCR was 76.6% (23/30) and LCR was 93.3% (28/30).
      When a combined calculation was made to determine the ability of the assays to
      detect patients infected in the cervix or urethra by testing FVU, the
      sensitivities dropped to 71.4% (25/35) for PCR and 80.0% (28/35) for LCR: CS
      sensitivity was 88.6% (31/35) for both amplified tests. There were two CS and
      five FVU false-positives by PCR which reduced to one CS and three FVU in the
      combined analysis. There were no false-positives by LCR. Inhibitors and low
      levels of chlamydial plasmid nucleic acids may have contributed to lower than
      expected sensitivities, suggesting a possible need for internal positive
      controls, especially for PCR, when testing urine. More studies with multiple
      sampling and more than one amplification assay are needed to confirm these
      findings and to identify and remove inhibitors of amplification assays.

PMID- 9281410
TI  - Cloning of the antigen 85A from Mycobacterium gordonae and its use for the
      specific PCR identification of these mycobacteria.
AB  - The complete nucleotide sequence of 85A antigen of Mycobacterium gordonae was
      determined. This gene encodes 339 amino acids, including 43 amino acids for the
      signal peptide, followed by a mature protein of 296 amino acids. A polymerase
      chain reaction (PCR) assay for the rapid detection of M. gordonae DNA using two
      pairs of oligonucleotide primers, derived from our sequence, is described. This
      one-step PCR has been used successfully to amplify 38 strains of M. gordonae.
      Conversely, the primers did not amplify DNA from any of the 25 mycobacterial
      species tested. The results suggest that this PCR assay could be a good
      alternative to existing commercial assays for the specific identification of M.
      gordonae on early culture on solid medium or on early BACTEC broth culture.

PMID- 9281411
TI  - PCR detection of Ruminococcus spp. in human and animal faecal samples.
AB  - Polymerase chain reaction (PCR) procedures for Ruminococcus spp. were developed
      and used for the detection of Ruminococcus spp. in human and animal faeces. The
      PCR specificity was established for Ruminococcus albus, R. bromii, R. obeum, R.
      callidus and R. flavefaciens. The PCR sensitivity ranged from 4 to 100 cells of
      the pure cultures, depending on the species. Ruminococcus albus, R. bromii, R.
      obeum and R. callidus were detected in human faeces. R. bromii, R. albus and R.
      obeum were also detected in animal faeces. R. flavefaciens was not detected in
      most of the samples tested, except for a weak positive in monkey faecal
      specimens. The PCR appears to be a specific and efficient method for the
      detection of Ruminococcus spp. in faecal specimens.

PMID- 9281412
TI  - Rapid PCR with nested primers for direct detection of Campylobacter jejuni in
      chicken washes.
AB  - Rapid detection of Campylobacter jejuni by PCR directly from foods, without prior
      growth steps, would be beneficial for the poultry industry. We have previously
      reported a PCR assay that allows detection of this bacterium after 48 h growth on
      Campy cefex agar. We have now developed a more rapid nested PCR assay that
      specifically detects C. jejuni in chicken washes that have not undergone any
      lengthy growth steps prior to PCR. For the nested reaction, an external set of
      primers, C-1 and C-4, are used for 24 cycles. At this time, 1 microl of the PCR
      product is removed and added to a second reaction. The second PCR assay is run
      with C-1 and an internal primer, C-2, for 24 cycles. A single band on a 4%
      NuSieve agarose gel at 122 bp was apparent with C. jejuni cells at a sensitivity
      of 10(2) cfu ml-1. With this method chicken carcasses can be washed and C. jejuni
      identified all within 1 day. We detected C. jejuni in approximately 80% of four
      groups of chickens using this method. The identifications have been confirmed by
      standard microbiological techniques.

PMID- 9281414
TI  - Detection of Mycobacterium tuberculosis by PCR analysis of urine and other
      clinical samples from AIDS and non-HIV-infected patients.
AB  - A number of different clinical specimens, such as sputum, cerebrospinal fluid and
      blood, have been reported to be good substrates for the detection of
      Mycobacterium tuberculosis by PCR assay. We wanted to search for the presence of
      mycobacteria in other body fluids, such as urine. Urine samples and other samples
      obtained from AIDS patients and non HIV-infected patients were analysed by PCR.
      The results were compared with those obtained using conventional methods (Bactec
      460 TB and AFB (acid fast bacilli strain)). We analysed 412 urine samples and 210
      different other samples (sputum and cerebrospinal fluid) obtained from AIDS
      patients by PCR; almost identical levels of PCR-positive (14-17%) results were
      observed in all samples analysed. The results were then compared with those
      obtained with the Bactec 460 TB and AFB. PCR, Bactec 460 TB and acid fast stain
      were also used to analyse 190 urine samples and 230 other samples from non-HIV
      infected patients in the consumption ward of Sassari Hospital. The number of
      urine samples positive by PCR (6.3%) and Bactec 460 TB (2.1%) was half that
      obtained from samples taken from the AIDS patients. As expected, an increase in
      the number of positive sputum samples was observed with all methods. The results
      indicate that PCR analysis of urine samples represents a valid alternative for
      fast and sensitive detection of M. tuberculosis. This method can be routinely
      used in the clinical laboratory, especially in HIV-infected patients.

PMID- 9281413
TI  - Rapid in situ hybridization technique for the detection of ribonucleic acids in
      tissues using radiolabelled and fluorescein-labelled riboprobes.
AB  - In situ hybridization (ISH) is a useful diagnostic and research tool, but is also
      time consuming. This study was conducted to determine if a rate enhancement
      hybridization (REH) buffer, developed for membrane hybridization, could be used
      to decrease hybridization time for ISH. Tissue from swine with an enteric disease
      produced by a swine coronavirus, transmissible gastroenteritis virus (TGEV), was
      used as a model to standardize hybridization conditions for a rapid ISH
      technique. Small intestinal sections from pigs experimentally and naturally
      infected with TGEV were hybridized for various times at 52 degrees C and 70
      degrees C with a radiolabelled or a fluorescein-labelled RNA probe in a standard
      hybridization or a REH buffer. Viral RNA was detected in intestines from as early
      as 30 min of hybridization by using both buffers with the radiolabelled probe;
      however, the signal was stronger with the REH buffer. With the fluorescein
      labelled probe, viral RNA was detected in virus-infected cells of the intestines
      after 30 min of hybridization by using the REH buffer. Signal intensity was
      greater with the REH buffer than with the standard hybridization buffer when
      compared at each hybridization time and hybridization temperature using both
      radiolabelled and fluorescein-labelled probes. With the REH buffer, hybridization
      signal intensity was greater at 70 degrees C than at 52 degrees C for both
      probes. The best results were obtained when small intestinal sections were
      hybridized at 70 degrees C for 2 h using a radiolabelled or a fluorescein
      labelled probe diluted in the REH buffer. The fluorescein-labelled RNA probe with
      REH buffer resulted in a minimal non-specific signal when compared with the
      radiolabelled probe. These studies demonstrated that the REH buffer can be used
      to decrease the time of ISH for the detection of viral RNA. This rapid ISH
      technique should have broad applications in the utilization of probe technology
      in diagnostics and research for the detection of target ribonucleic acids in situ

PMID- 9281415
TI  - Combined SSCP/heteroduplex analysis in the screening for PAX6 mutations.
AB  - We demonstrate the use of combined SSCP and heteroduplex analysis in the
      detection of PAX6 mutations using non-radioactive silver staining. A panel of
      aniridia patients was screened by this approach and we show that a greater number
      of mutations was detected than would have been found by running each technique
      alone. Six previously unreported aniridia mutations in PAX6 are also described..

PMID- 9281416
TI  - Acute intermittent porphyria: the in vitro expression of mutant
      hydroxymethylbilane synthase.
AB  - Acute intermittent porphyria (AIP) is an inborn error of haem biosynthesis caused
      by a variety of mutations in the gene coding for hydroxymethylbilane synthase
      (HMB-S). The entire coding sequence of this gene, from each of three South
      African AIP patients, was therefore screened for mutations using chemical
      cleavage mismatch (CCM) analysis and any changes detected characterized by DNA
      sequencing. Three single base changes were identified; a G77 to A in exon 3, a
      C346 to T in exon 8 and a G518 to A in exon 10. These missense mutations,
      previously reported to be present in other populations, are known to be
      responsible for the structurally deleterious amino acid replacements R26H, R116W
      and R173Q, respectively. The in vitro expression of the enzymes containing these
      mutations and the subsequent measurement of their specific activities revealed a
      reduction to approximately 4% of normal activity.

PMID- 9281417
TI  - Rapid, sensitive, microbial detection by gene amplification using restriction
      endonuclease target sequences.
AB  - The use of primers synthesized to eight class II restriction endonuclease target
      sequences, from Haemophilus parainfluenzae, Escherichia coli, Staphylococcus
      aureus, Salmonella infantis, Rhodobacter sphaeroides, Klebsiella pneumoniae,
      Bacillus amyloliquefaciens and Proteus vulgaris for single and multiplex PCR
      identification of the organisms is discussed. Results indicate that the method is
      sensitive and specific enough to detect single cells and attogram amounts of
      target DNA. It has also been demonstrated that the primers can be used in whole
      cell PCR for identification and whole cell PCR product recovery could be enhanced
      by the addition of gelatin or DMSO to PCR reaction mixtures. Other results have
      indicated that the method can be used for the definite identification of specific
      individuals present in mixed cultures or suspensions of organisms. The
      applicability of the method for detection of a specific strain within a group of
      closely related organisms has also been investigated and for that
      sequence/organism the results suggest that the proposed method is indeed very
      specific and discriminative. It is suggested that as more information becomes
      available regarding such sequences and their distribution, this approach could
      form the basis of a widescale, rapid, simple and cheap identification and/or
      typing system for bacteria.

PMID- 9281418
TI  - PstI RFLP in the GABA rho1 receptor gene on human chromosome 6q.

PMID- 9281419
TI  - A frequent polymorphism in the 5' region of the BCMA gene.

PMID- 9281420
TI  - DNA typing of HLA-B27 by polymerase chain reaction.
AB  - To find a specific method for HLA-B27 typing, we tested an HLA-B27-specific
      polymerase chain reaction. This method was used for screening 100 randomly
      selected blood donors, 10 of them being HLA-B27 positive. A flow cytometric
      method and this PCR method were compared.

PMID- 9281421
TI  - Reported translational bypass in a trpR'-lacZ' fusion is accounted for by unusual
      initiation and +1 frameshifting.
AB  - I. Benhar and H. Engelberg-Kulka reported that a 55 nucleotide translational
      bypass occurs in decoding a fusion of the Escherichia coli tryptophan repressor,
      trpR, and lacZ genes. The start of the bypass occurred in the trpR gene and
      coding resumed in the lacZ gene. It was considered that bypassing likely occurred
      in expression of trpR itself to produce an additional 10 kDa product which may be
      biologically important. We report here that bypass is undetectable in the same
      and related trpR'-lacZ' fusions. The beta-galactosidase activity derived from the
      fusions is accounted for by unusual internal initiation and +1 frameshifting,
      both of which occur in the lacZ part of the fusion. The 10 kDa product reportedly
      encoded by the trpR gene was not detectable to a level of 1% of the full-length
      12 kDa tryptophan repressor product, at least when expressed from a T7 promoter.

PMID- 9281422
TI  - Long-range effects in a supercoiled DNA domain generated by transcription in
      vitro.
AB  - The translocation of a transcription complex can transiently introduce positive
      and negative superhelical windings into the template DNA. To gain further insight
      into this dynamic DNA supercoiling mechanism and its possible involvement in
      biological processes, we employed an in vitro system in which site-specific
      recombination by gammadelta resolvase is topologically coupled to transcription
      induced negative supercoiling. Our kinetic experiments suggest that recombination
      is closely linked to the process of supercoiling by transcription. We utilized
      the known high speed at which two resolvase-bound recombination sites can pair to
      form a synaptic complex in kinetic experiments with DNA substrates containing
      three recombination sites. Our data provide evidence for the existence of a
      transient gradient of negative supercoiling. Such a gradient seems to be
      predominantly a consequence of DNA double helix rotation behind a translocating
      RNA polymerase and originates within a broad region up to two kilobase-pairs
      upstream of the transcriptional start site. We further demonstrate that the
      topological coupling between transcription and recombination is not affected when
      the DNA-bending protein integration host factor from E. coli is bound to multiple
      sites within the phage lambda attachment region. We discuss implications of our
      in vitro findings with respect to possible in vivo functions of the dynamic
      nature of transcription-induced supercoiling.

PMID- 9281423
TI  - Correlated mutations contain information about protein-protein interaction.
AB  - Many proteins have evolved to form specific molecular complexes and the
      specificity of this interaction is essential for their function. The network of
      the necessary inter-residue contacts must consequently constrain the protein
      sequences to some extent. In other words, the sequence of an interacting protein
      must reflect the consequence of this process of adaptation. It is reasonable to
      assume that the sequence changes accumulated during the evolution of one of the
      interacting proteins must be compensated by changes in the other. Here we apply a
      method for detecting correlated changes in multiple sequence alignments to a set
      of interacting protein domains and show that positions where changes occur in a
      correlated fashion in the two interacting molecules tend to be close to the
      protein-protein interfaces. This leads to the possibility of developing a method
      for predicting contacting pairs of residues from the sequence alone. Such a
      method would not need the knowledge of the structure of the interacting proteins,
      and hence would be both radically different and more widely applicable than
      traditional docking methods. We indeed demonstrate here that the information
      about correlated sequence changes is sufficient to single out the right inter
      domain docking solution amongst many wrong alternatives of two-domain proteins.
      The same approach is also used here in one case (haemoglobin) where we attempt to
      predict the interface of two different proteins rather than two protein domains.
      Finally, we report here a prediction about the inter-domain contact regions of
      the heat- shock protein Hsc70 based only on sequence information.

PMID- 9281424
TI  - A new model for the three-dimensional folding of Escherichia coli 16 S ribosomal
      RNA. I. Fitting the RNA to a 3D electron microscopic map at 20 A.
AB  - Recently published models of the Escherichia coli 70 S ribosome at 20 A
      resolution, obtained by cryo-electron microscopy (cryo-EM) combined with
      computerized image processing techniques, exhibit two features that are directly
      relevant to the in situ three-dimensional folding of the rRNA molecules. First,
      at this level of resolution many fine structural details are visible, a number of
      them having dimensions comparable to those of nucleic acid helices. Second, in
      reconstructions of ribosomes in the pre- and post-translocational states, density
      can be seen that corresponds directly to the A and P site tRNAs, and to the P and
      E site tRNAs, respectively, thus enabling the decoding region on the 30 S subunit
      to be located rather precisely. Accordingly, we have refined our previous model
      for the 16 S rRNA, based on biochemical evidence, by fitting it to the cryo-EM
      contour of ribosomes carrying A and P site tRNAs. For this purpose, the most
      immediately relevant evidence consists of new site-directed cross-linking data in
      the decoding region, which define sets of contacts between the 16 S rRNA and
      mRNA, or between 16 S rRNA and tRNA at the A, P and E sites; these contact sites
      can be correlated directly with the tRNA positions in the EM structure. The model
      is extended to other parts of the 16 S molecule by fitting individual elements of
      the well-established secondary structure of the 16 S rRNA into the appropriate
      fine structural elements of the EM contour, at the same time taking into account
      other data used in the previous model, such as intra-RNA cross-links within the
      16 S rRNA itself. The large body of available RNA-protein cross-linking and foot
      printing data is also considered in the model, in order to correlate the rRNA
      folding with the known distribution of the 30 S ribosomal proteins as determined
      by neutron scattering and immuno-electron microscopy. The great majority of the
      biochemical data points involve single-stranded regions of the rRNA, and
      therefore, in contrast to most previous models, the single-stranded regions are
      included in our structure, with the help of a specially developed modelling
      programme, ERNA-3D. This allows the various biochemical data sets to be displayed
      directly, in this and in the accompanying papers, on diagrams of appropriate
      parts of the rRNA structure within the cryo-EM contour.

PMID- 9281425
TI  - A new model for the three-dimensional folding of Escherichia coli 16 S ribosomal
      RNA. II. The RNA-protein interaction data.
AB  - The map of the mass centres of the 21 proteins from the Escherichia coli 30 S
      ribosomal subunit, as determined by neutron scattering, was fitted to a
      cryoelectron microscopic (cryo-EM) model at a resolution of 20 A of 70 S
      ribosomes in the pre-translocational state, carrying tRNA molecules at the A and
      P sites. The fit to the 30 S moiety of the 70 S particles was accomplished with
      the help of the well-known distribution of the ribosomal proteins in the head,
      body and side lobe regions of the 30 S subunit, as determined by immuno electron
      microscopy (IEM). Most of the protein mass centres were found to lie close to the
      surface (or even outside) of the cryo-EM contour of the 30 S subunit, supporting
      the idea that the ribosomal proteins are arranged peripherally around the rRNA.
      The ribosomal protein distribution was then compared with the corresponding model
      for the 16 S rRNA, fitted to the same EM contour (described in an accompanying
      paper), in order to analyse the mutual compatibility of the arrangement of
      proteins and rRNA in terms of the available RNA-protein interaction data. The
      information taken into account included the hydroxyl radical and base foot
      printing data from Noller's laboratory, and our own in situ cross-linking
      results. Proteins S1 and S14 were not considered, due to the lack of RNA-protein
      data. Among the 19 proteins analysed, 12 (namely S2, S4, S5, S7, S8, S9, S10,
      S11, S12, S15, S17 and S21) showed a fit to the rRNA model that varied from being
      excellent to at least acceptable. Of the remaining 7, S3 and S13 showed a rather
      poor fit, as did S18 (which is considered in combination with S6 in the foot
      printing experiments). S16 was difficult to evaluate, as the foot-print data for
      this protein cover a large area of the rRNA. S19 and S20 showed a bad fit in
      terms of the neutron map, but their foot-print and cross-link sites were
      clustered into compact groups in the rRNA model in those regions of the 30 S
      subunit where these proteins have respectively been located by IEM studies.

PMID- 9281426
TI  - A new model for the three-dimensional folding of Escherichia coli 16 S ribosomal
      RNA. III. The topography of the functional centre.
AB  - We describe the locations of sites within the 3D model for the 16 S rRNA
      (described in two accompanying papers) that are implicated in ribosomal function.
      The relevant experimental data originate from many laboratories and include sites
      of foot-printing, cross-linking or mutagenesis for various functional ligands. A
      number of the sites were themselves used as constraints in building the 16 S
      model. (1) The foot-print sites for A site tRNA are all clustered around the
      anticodon stem-loop of the tRNA; there is no "allosteric" site. (2) The foot
      print sites for P site tRNA that are essential for P site binding are similarly
      clustered around the P site anticodon stem-loop. The foot-print sites in 16 S
      rRNA helices 23 and 24 are, however, remote from the P site tRNA. (3) Cross-link
      sites from specific nucleotides within the anticodon loops of A or P site-bound
      tRNA are mostly in agreement with the model, whereas those from nucleotides in
      the elbow region of the tRNA (which also exhibit extensive cross-linking to the
      50 S subunit) are more widely spread. Again, cross-links to helix 23 are remote
      from the tRNAs. (4) The corresponding cross-links from E site tRNA are
      predominantly in helix 23, and these agree with the model. Electron microscopy
      data are presented, suggestive of substantial conformational changes in this
      region of the ribosome. (5) Foot-prints for IF-3 in helices 23 and 24 are at a
      position with close contact to the 50 S subunit. (6) Foot-prints from IF-1 form a
      cluster around the anticodon stem-loop of A site tRNA, as do also the sites on 16
      S rRNA that have been implicated in termination. (7) Foot-print sites and
      mutations relating to streptomycin form a compact group on one side of the A site
      anticodon loop, with the corresponding sites for spectinomycin on the other side.
      (8) Site-specific cross-links from mRNA (which were instrumental in constructing
      the 16 S model) fit well both in the upstream and downstream regions of the mRNA,
      and indicate that the incoming mRNA passes through the well-defined "hole" at the
      head-body junction of the 30 S subunit.

PMID- 9281427
TI  - Solution scattering structural analysis of the 70 S Escherichia coli ribosome by
      contrast variation. I. Invariants and validation of electron microscopy models.
AB  - Solutions of selectively deuterated 70 S Escherichia coli ribosomes and of free
      30 S and 50 S subunits were studied by neutron scattering using contrast
      variation. The integrity of the partially deuterated particles was controlled by
      parallel X-ray measurements. Integral parameters of the entire ribosome, of its
      subunits and of the protein and rRNA moieties were evaluated. The data allow an
      experimental validation of the two most recent electron microscopy
      reconstructions of the 70 S ribosome presented by the groups of J. Frank (Albany)
      and of M. van Heel & R. Brimacombe (Berlin). For each reconstruction, integral
      parameters and theoretical scattering curves from the 70 S and its subunits were
      calculated and compared with the experimental data. Although neither of the two
      models yields a comprehensive agreement with the experimental data, Frank's model
      provides a better fit. For the 50 S subunit of van Heel & Brimacombe's model the
      fit with the experimental data improves significantly when the internal channels
      and tunnels are filled up. The poorer fit of the latter model is thus caused by
      its "sponge"-like structure which may partly be due to an enhancement of high
      frequency contributions in some of the steps of the three-dimensional image
      reconstruction. It seems therefore unlikely that the ribosome has a "sponge"-like
      structure with a pronounced network of channels.

PMID- 9281428
TI  - Solution scattering structural analysis of the 70 S Escherichia coli ribosome by
      contrast variation. II. A model of the ribosome and its RNA at 3.5 nm resolution.
AB  - Selectively deuterated 70 S E. coli ribosomes and isolated 30 S and 50 S subunits
      were analyzed by X-ray and neutron solution scattering. The resulting contrast
      variation data set (42 curves in total) was proven to be consistent in describing
      the ribosome as a four-phase system composed of the protein and rRNA moieties of
      both subunits. This data set thus provides ten times more information than a
      single scattering curve. A solid body four-phase model of the 70 S ribosome at
      low resolution was built from the envelope functions of the 30 S and 50 S
      subunits and of those of the corresponding RNA moieties. The four envelopes were
      parameterized at a resolution of 3.5 nm using spherical harmonics and taking into
      account interface layers between the phases. The initial approximation for the
      envelopes of the subunits was taken from electron microscopic data presented
      recently by J. Frank and co-workers (Albany); the rRNA envelopes were initially
      approximated by spheres. The optimization and the refinement of the model
      proceeded by non-linear least squares minimization fitting the available
      experimental data. The refined envelopes of the subunits differ by about 10% from
      the starting approximation and the shape of the final 70 S model lies between the
      outer envelopes of the models by Frank and by M. von Heel & R. Brimacombe
      (Berlin). The rRNA moiety in the 30 S subunit is more anisometric than the
      subunit itself, whereas the rRNA of the 50 S subunit forms a compact core. The
      rRNAs protrude to the surfaces of the subunits and occupy approximately 30 to 40%
      of the corresponding surface areas. X-ray scattering curves of the two main
      functional elongation 70 S complexes (pre- and post-translocational) differ only
      marginally from those of the non-programmed ribosomes, suggesting that the low
      resolution four-phase model is also valid for the elongating 70 S ribosome.

PMID- 9281429
TI  - Crystal structures of a mutant maltotetraose-forming exo-amylase cocrystallized
      with maltopentaose.
AB  - The three-dimensional structures of the catalytic residue Glu219-->Gln mutant of
      Pseudomonas stutzeri maltotetraose-forming exo-alpha-amylase, and its complex
      with carbohydrate obtained by cocrystallization with maltopentaose were
      determined. Two crystal forms were obtained for the complexed enzyme, and a bound
      maltotetraose was found in each. The structures were analyzed at 2.2 A and 1.9 A
      resolution, respectively for the uncomplexed and complexed mutant. These
      structures were compared with the wild-type enzyme structure. In the complexed
      crystals, the maltotetraose was firmly bound, extensively interacting with the
      amino acid environments in the active cleft. The non-reducing end glucose unit
      was hydrogen bonded to the side-chain of Asp160 and the main-chain nitrogen of
      Gly158, which seem to be predominantly required for the recognition of the non
      reducing end of the substrate that determines the exo-wise degradation of this
      enzyme. The reducing end glucose unit of bound maltotetraose showed clear
      deformation, adopting a half-chair conformation with extensive hydrogen bonds to
      surrounding polypeptides. The C1-atom of this deformed glucose unit lies very
      close to Asp193OD1 with a distance of 2.6 A. The catalytic residue Asp294 is
      firmly hydrogen-bonded to the O2 and O3-hydroxyl groups of the deformed reducing
      end glucose unit. Upon binding of the carbohydrate, small but significant induced
      fits were observed in the regions of Asp294, Phe156, Ile157, and Asp160. Possible
      roles of the three catalytic residues are also discussed.

PMID- 9281430
TI  - Thermus thermophilus cytochrome-c552: A new highly thermostable cytochrome-c
      structure obtained by MAD phasing.
AB  - The three-dimensional structure of cytochrome-c552 from Thermus thermophilus has
      been determined by the multiple anomalous dispersion technique using synchrotron
      radiation and refined to a resolution of 1.28 A. Data collection at 90 K and the
      recording of three data sets (f'-minimum: 7125 eV, f"-maximum: 7138 eV and
      reference for scaling: 10,077 eV) resulted in an initial electron density of very
      high quality at 2.1 A, which was readily interpretable for model building. The
      model was refined to an R value of 19.1% (Rfree=22.4%) at 1.28 A resolution using
      a fourth data set collected at a photon energy of 11,810 eV. Comparison of this
      thermophilic cytochrome with its mesophilic mitochondrial or bacterial
      counterparts reveals significant structural differences which are discussed with
      respect to their importance for thermostability and binding between this
      cytochrome and its corresponding ba3-oxidase. Amino acid sequence similarities to
      other class I cytochromes are very weak and entirely limited to the region around
      the CXXCH motif close to the N terminus. The N-terminal two-thirds of cytochrome
      c552 cover spatial regions around the heme prosthetic group that are similar to
      those observed for other cytochromes. The actual secondary structural elements
      that are responsible for that shielding do not, however, correlate well to other
      structures. Only the N-terminal helix (containing the heme binding cysteine
      residues) aligns reasonably well with other class I cytochromes. The most
      striking differences that distinguish the present structure from all other class
      I cytochromes is the C-terminal one-third of the molecule that wraps around the
      remainder of the structure as a stabilizing clamp, the existence of an extended
      beta-sheet covering one edge of the heme and the lack of any internal water
      molecule.

PMID- 9281431
TI  - Ca2+-loaded spherulin 3a from Physarum polycephalum adopts the prototype gamma
      crystallin fold in aqueous solution.
AB  - Spherulin 3a is the most abundantly expressed cytosolic protein in spherulating
      plasmodia of the slime mold Physarum polycephalum. High yields of unlabeled,
      uniformly 15N and uniformly 13C/15N-labeled recombinant spherulin 3a from
      Escherichia coli could be produced by a simple protocol described here. The three
      dimensional solution structure of Ca2+-loaded spherulin 3a was determined by homo
      and heteronuclear NMR spectroscopy. The structure of monomeric spherulin 3a
      consists of two pleated beta-sheets plus a short alpha-helix arranged into the
      gamma-crystallin fold. The beta-sheets comprise two intertwined Greek-key motifs.
      An additional N-terminal beta-strand is unique to spherulin 3a. Complexation of
      calcium ions greatly enhances overall conformational stability of the protein.
      The average atomic root-mean-square deviations (r.m.s.d.) for heavy atoms in beta
      strands were 0.34(+/-0.16) A for the backbone atoms and 0.73(+/-0.40) A for all
      atoms. The corresponding r.m.s.d. values for heavy atoms in the whole protein
      were 0.62(+/-0.42) A for the backbone atoms and 0.99(+/-0.65) A for all atoms. We
      show the structural relationship between spherulin 3a, a myxomycete dormancy
      protein, and crystallins from the vertebrate eye lens. Since spherulin 3a has a
      structure corresponding to one domain of bovine gammaB(II)-crystallin, it
      represents a hypothetical ancestral gamma-crystallin precursor structure.

PMID- 9281433
TI  - Regulation of the Na+/H+ exchanger in the mammalian myocardium.

PMID- 9281432
TI  - Consideration of the pH-dependent inhibition of dihydrofolate reductase by
      methotrexate.
AB  - Poisson-Boltzmann calculations were used to determine the pKa of protein
      functional groups in the unliganded dihydrofolate reductase enzyme, and the pKa
      of protein and ligand groups in methotrexate-enzyme complexes. The results
      reported here are in conflict with two fundamental tenets of dihydrofolate
      reductase inhibition by methotrexate: (1) Asp27 is not expected to be protonated
      near pH 6.5 in the apoenzyme as previously proposed based on fitting of empirical
      equations to binding data, and (2) the calculated pKa for the pteridine N1 of the
      inhibitor while bound to the protein is significantly lower than that estimated
      for this group from interpretation of NMR data (>10). In fact, the electrostatic
      calculations and complementary quantum chemical calculations indicate that Asp27
      is likely protonated when methotrexate is bound, resulting in a neutral dipole
      dipole interaction rather than a salt-bridge between the enzyme and the
      inhibitor. Reasons for this discrepancy with the experimental data are discussed.
      Furthermore, His45 and Glu17 in the Escherichia coli enzyme are proposed to be in
      part responsible for the pH dependence of the conformational degeneracy in the
      inhibitor-enzyme complex.

PMID- 9281434
TI  - Fibrous tissue and angiotensin II.
AB  - Myofibroblasts (myoFb) are cells responsible for fibrous tissue formation in
      injured systemic organs such as the heart. Cultured myoFb, obtained from rat
      cardiac scar tissue, express genes that encode components requisite for
      angiotensin (Ang) II generation, which in turn regulates myoFb collagen turnover
      in an autocrine/paracrine manner. In this study, we tested the hypothesis that
      these wound-healing fibroblast-like cells and locally generated Ang II are
      involved in other repairing tissue. To test this hypothesis, we used a granuloma
      pouch model, where a subcutaneous air sac is created followed by injection of
      croton oil. Pouch tissue was collected at days 4, 7, 14 and 21. The presence of
      myoFb was determined by immunohistochemical alpha-smooth muscle actin (alpha-SMA)
      labeling and collagen accumulation by picrosirius red staining. Angiotensin
      converting enzyme (ACE) and Ang II receptor binding were detected by in vitro
      quantitative autoradiography using 125I-351A and 125I[Sar1, Ile8]Ang II,
      respectively, while Ang II receptor subtype was defined by displacement studies
      using either an AT1 (losartan) or AT2 (PD123177) receptor antagonist. Cells
      expressing ACE were determined by immunohistochemistry. Ang II content in pouch
      tissue was measured by radioimmunoassay following HPLC separation while its
      capacity to generate Ang II was assessed in tissue bath, with and without
      exogenous Ang I or lisinopril, an ACE inhibitor. Collagen accumulation in pouch
      tissue was examined by determining hydroxyproline content in response to
      lisinopril, AT1 or AT2 receptor antagonists (losartan or PD123177). In pouch
      tissue, we found: (1) myoFb at day 4 which became more extensive at days 7, 14
      and 21; (2) morphologic evidence of collagen deposition evident at day 4, which
      gradually became more extensive thereafter; (3) ACE and Ang II receptor binding
      was evident at day 4 and remained invariant on days 7, 14 and 21; (4) the
      predominant Ang II receptor subtype expressed was AT1; (5) myoFb express ACE and
      AT1 receptors; (6) picogram quantities of Ang II (per g tissue) was evident on
      days 7, 14 and 21; and (7) Ang II was generated from Ang I substrate. Lisinopril
      and losartan, but not PD123177, significantly attenuated pouch weight and
      accumulation of collagen. Thus, in this model of cutaneous repair, the appearance
      of myoFb is associated with Ang II generation that regulates fibrogenesis by AT1
      receptor binding. Signals involved in the appearance of myoFb remain uncertain.
      Further studies are required to address the regulation of Ang II generation in
      pouch tissue of the rat.

PMID- 9281435
TI  - The effect of CY1503, a sialyl Lewisx analog blocker of the selectin adhesion
      molecules, on infarct size and "no-reflow" in the rabbit model of acute
      myocardial infarction/reperfusion.
AB  - CY1503, an analogue of sialyl-Lewisx, is an inhibitor of the selectin adhesion
      molecules. CY1503 has been found to limit myocardial infarct size in canine and
      feline models. However, the effect of CY1503 on the "no-reflow" phenomenon is
      still unknown. Anesthetised rabbits were subjected to 30 min of coronary artery
      occlusion and 4 h of reperfusion. Protocol 1: after 27 min of ischemia, rabbits
      were randomised to an iv bolus of either CY1503 (30 mg/kg) (n=9) or saline (n=9).
      Protocol 2: rabbits were randomly given two iv boluses of CY1503 (30 mg/kg) (n=6)
      or saline (n=6), administered after 10 and 25 min of ischemia. Protocol 3: after
      27 min of ischemia rabbits were randomly given an iv bolus of CY1503 (30 mg/kg)
      (n=6) and infusion of 20 mg/kg over 4 h or saline bolus+infusion (n=6). Regional
      myocardial blood flow (RMBF) was assessed after 30 min and 4 h of reperfusion.
      The risk zone (RZ) was assessed by blue dye and the necrotic zone (NZ) by
      tetrazolium staining. RMBF: protocol 1: RMBF in the RZ was 2.19+/-0.33 v 2. 34+/
      0.34 ml/g/min in CY1503 and controls at 30 min (P=0.75), and 0. 43+/-0.07 v
      0.41+/-0.08 at 4 h of reperfusion (P=0.85). The corresponding results for
      protocol 2 were 1.77+/-0.29 v 1.53+/-0.34 at 30 min (P=0.61) and 0.53+/-0.16 v
      0.91+/-0.55 at 4 h (P=0.53). RMBF in RZ in protocol 3 were 1.52+/-0.25 v 1.32+/
      0.20 at 30 min (P=0.56) and 0.30+/-0.05 v 0.29+/-0.09 (P=0.90) after 4 h of
      reperfusion. The RZ was similar in both groups in all protocols. The NZ/RZ ratio
      was comparable in the CY1503 and control group in all three protocols (0.32+/
      0.04 v 0.37+/-0.06, 0.37+/-0.08 v 0.33+/-0. 07, and 0.51+/-0.05 v 0.38+/-0.05 in
      protocols 1, 2, and 3, respectively). CY1503 did not limit infarct size or
      prevent the "no-reflow" phenomenon in the rabbit.

PMID- 9281436
TI  - IGF-I and bFGF differentially influence atrial natriuretic factor and alpha
      smooth muscle actin expression in cultured atrial compared to ventricular adult
      rat cardiomyocytes.
AB  - In the present study, we compare expression, storage and secretion of the atrial
      natriuretic factor (ANF) in atrial and ventricular adult rat cardiomyocytes (aARC
      and vARC) in long-term culture. The influence of insulin-like growth factor-I
      (IGF-I) and of basic fibroblast growth factor (bFGF) on ANF production and
      secretion, as well as on the expression of a structural component, alpha-smooth
      muscle actin (alpha-sm actin), was studied in the two cell types. Antibodies
      against alpha-ANF were used for immunocytochemical localization of ANF. aARC
      contained more ANF-granules than vARC, and they were distributed throughout the
      cell bodies. Quantitative determination of ANF storage and secretion was done by
      radioimmunoassay (RIA; 125I), and it was demonstrated that aARC stored and
      secreted ANF 18- and 16-times more, respectively, when compared to vARC. Immuno
      electron microscopy confirmed that ANF storing secretory granules were present in
      both types of cardiomyocytes. Expression of ANF and alpha-sm actin in aARC and
      vARC responded differently to treatment with either IGF-I or bFGF. In aARC,
      neither IGF-I nor bFGF had an influence on expression of ANF. In vARC, expression
      of ANF was downregulated by IGF-I and upregulated by bFGF with regard to both
      immunoreactivity and message. In contrast to vARC, expression of alpha-sm actin
      was not affected by IGF-I in aARC, whereas bFGF produced a strong upregulation
      similar to that found in vARC. Mitogen-activated protein kinases (MAPK) 42 and
      44, though, were equally activated by bFGF and IGF-I in both aARC and vARC.

PMID- 9281437
TI  - Vinculin is an essential component for normal myofibrillar arrangement in fetal
      mouse cardiac myocytes.
AB  - Vinculin is a cytoskeletal protein that is believed to be an essential component
      in the linkage of cytoskeletal actin filaments to the plasma membrane. To
      investigate the precise function of vinculin in the development of cardiac
      myofibrils, antisense oligodeoxynucleotides complementary to vinculin mRNA were
      used to perturb the expression of the protein during myofibril assembly and
      arrangement in mouse cardiac myocytes. Fetal (day 18-20 post-conception) mouse
      cardiac myocytes were isolated by collagenase digestion, separated by Percoll
      density gradient centrifugation, and plated on aligned collagen gels. By 72 h of
      culture, mouse myocytes displayed an elongated in vivo-like phenotype in parallel
      with the aligned fibrils of the collagen gels with polarized arrays of
      myofibrils. Two different antisense oligonucleotides (20-mer) altered the
      formation of the tissue-like phenotype of myocytes. These antisense
      oligonucleotides suppressed vinculin protein expression at 43.5+/-26.8% and
      48.7+/-20.9% when compared to myocytes that were not treated. Examination of
      these myocytes by confocal scanning laser and transmission electron microscopy
      revealed a disruption of the aligned in vivo-like phenotype, assembly of thick
      and thin filaments, and formulation of Z-bands. Random sequence 20-mer
      oligonucleotides used as controls had little detectable effect on vinculin
      protein expression (94.2+/-14.8%), cell shape, normal alignment or assembly of
      myofibrils. These results indicate that vinculin is a critical cytoskeletal
      component, that functions in the determination of cell shape and the arrangement
      and organization of developing myofibrils.

PMID- 9281438
TI  - Different responses of non-ischemic and post-ischemic myocardium towards Ca2+
      sensitization.
AB  - We tested whether decreased Ca2+ sensitivity is a major cause for dysfunctional
      stunned myocardium. The experiments employed a novel Ca2+ sensitizing agent: the
      thiadiazinone derivative EMD 60 263. Experiments were done on 14 isolated, blood
      perfused rabbit hearts. After control, seven hearts were subjected to 20 min no
      flow ischemia, and then allowed to recover during 30 min reperfusion. Thereafter,
      EMD 60 263 was administered (3, 10 and 30 microm). For comparison, the effect of
      the same doses was investigated in seven non-ischemic hearts. At the low dose,
      the agent improved ventricular systolic function in the post-ischemic group
      significantly (LVPmax: 65+/-13 v 91+/-17 mmHg; dP/dtmax: 845+/-235 v 1300+/-350
      mmHg/s), and non-significantly in the non-ischemic group (LVPmax: 115+/-35 v
      132+/-39 mmHg; dP/dtmax: 1415+/-545 v 1885+/-720 mmHg/s). Early relaxation
      (dP/dtmin) was slightly improved in both groups (800+/-225 v 1050+/-220 mmHg/s
      post-ischemic; 1120+/-315 v 1205+/-285 mmHg/s non-ischemic). Heart rate was
      increased (151+/-35 v 175+/-45 beats/min) in the post-ischemic group and was
      unaffected in the non-ischemic group. At the higher dose, systolic ventricular
      function in the post-ischemic group was further improved (LVPmax: 109+/-17 mmHg,
      dP/dtmax: 1330+/-180 mmHg/s), but tended to decrease in the non-ischemic group
      (LVPmax: 121+/-40 mmHg, dP/dtmax: 1605+/-680 mmHg/s). This dose decreased heart
      rate in both groups (133+/-34 and 134+/-23 beats/min). 30 microm EMD 60 263 had
      deleterious effects in both groups. The different responses towards Ca2+
      sensitization suggest that a decrease in Ca2+ sensitivity might play a role in
      dysfunctional stunned myocardium. Therefore, Ca2+ sensitizing agents of the
      thiadiazinone type could be useful to recruit a positive inotropic reserve in
      stunned myocardium.

PMID- 9281439
TI  - In vivo and in vitro inhibition of the L-type calcium current in isolated guinea
      pig cardiomyocytes by the immunosuppressive agent cyclosporin A.
AB  - Cyclosporin A (CsA), an immunosuppressive agent used to reduce rejection after
      organ transplantation, induces secondary effects in heart tissue. We have studied
      the effects in vivo and in vitro of CsA on L-type Ca2+ current (ICa) and the
      associated gating currents of isolated guinea-pig ventricular myocytes using the
      whole-cell patch-clamp technique. For in vivo experiments, a group of animals
      (n=28) was treated for 21 days by subcutaneous injection of CsA (15 mg/kg/day).
      Blood level of CsA was 1191+/-221 ng/ml (n=9). In cells from these animals (n=65,
      19 animals), ICa was reduced to about 75% of that recorded from control cells
      (n=32, six animals). CsA decreased the availability of Ca2+ channels at
      potentials more positive than +30 mV. Isoproterenol (100 nM) was still able to
      increase ICa but only by 30+/-6% (n=9), whereas in control it increased ICa by
      290+/-22% (n=5). Gating currents related to L-type Ca2+ channels were not altered
      in cells from CsA-treated animals. In in vitro experiments, CsA reduced ICa when
      applied directly to cardiomyocytes. CsA affected the kinetics of ICa
      inactivation, slowing down the rapid phase and accelerating the slow phase (n=4).
      The steady-state inactivation curve of ICa was shifted to more negative voltages
      and the degree of availability at -80 mV decreased by in vitro application of
      CsA. The half inactivation potential (V1/2) changed from -23+/-0.6 mV in control
      to -31+/-2 mV, -48+/-0.6 mV and -49+/-0.6 mV, in 1, 50 and 80 microM CsA,
      respectively. In these cells, the gating currents related to L-type Ca2+ channels
      were also not altered by CsA. CsA does not modify the Ca2+ channel density,
      although it induces a decrease in the beta1-adrenergic stimulation of ICa. The
      results are explained by a direct effect on the calcium channel inactivation of
      CsA and a non specific indirect effect.

PMID- 9281441
TI  - Purification of endothelin from a conditioned medium of cardiac fibroblastic
      cells using beating rate assay of myocytes cultured in a serum-free medium.
AB  - A conditioned medium from cardiac fibroblastic cells stimulated the beating of
      quiescent cardiac myocytes cultured in a serum-free medium. The aim of this study
      was to isolate and characterize the myocyte beat-stimulating activity of the
      conditioned medium of fibroblastic cells. Cardiac myocytes and fibroblastic cells
      were isolated individually from neonatal rats. The fibroblastic cells were grown
      in a growth medium until they became confluent, then serum-free conditioned
      medium was obtained from them. For the beating-rate assay, the cardiac myocytes
      were cultured in a completely serum-free medium. The beat-stimulating factor of
      myocytes in the conditioned medium was purified by reverse-phase liquid
      chromatographies and gel filtration, and was characterized by measuring the
      molecular weight of the activity and a pharmacological antagonistic study. The
      beat-stimulating activity in the conditioned medium was purified into two active
      fractions. Both of the activities have a molecular weight of 2.5 kDa, and the
      activities were abolished similarly by FR139317, an endothelin type-A receptor
      antagonist. These results indicate that cardiac fibroblastic cells secrete
      endothelin and that this may contribute in part to the functional abnormalities
      of the heart in patients with myocardial fibrosis.

PMID- 9281440
TI  - Ethylisopropylamiloride diminishes changes in intracellular Na, Ca and pH in
      ischemic newborn myocardium.
AB  - Numerous studies suggest that in adult hearts myocardial ischemic injury is in
      part the result of proton stimulation of Na/H exchange which increases
      intracellular Na (Nai) and thus leads to increases in intracellular Ca
      concentration ( [Ca]i) due to changes in Na/Ca exchange flux. Corollary to the
      hypothesis, inhibition of Na/H exchange diminishes Na and Ca accumulation and
      improves heart function after ischemia. To test this hypothesis and its corollary
      in newborn hearts, NMR spectroscopy was used to measure intracellular pH (pHi),
      Nai, [Ca]i, and high energy phosphates in isolated, 4-7-day-old rabbit hearts,
      Langendorff-perfused with Krebs-Henseleit solution at pH 7.4+/-0.5 equilibrated
      with 95% O2/5% CO2 at 36+/-1 degrees C. Control hearts were perfused for 30 min
      before initiating 40 min of global ischemia followed by 40 min of reperfusion. In
      a second group of hearts ethylisopropylamiloride (EIPA-10 microM) was added to
      the perfusate 20 min before global ischemia to inhibit Na/H exchange. After 15
      min ischemia, pHi in EIPA-treated hearts (6.41+/-0.04) was higher than that of
      the control hearts (6.20+/-0.08; P<0.05). EIPA also limited the increase in Nai
      and [Ca]i during ischemia and improved Nai and [Ca]i recovery during reperfusion
      (P<0.05). Nai (mEq/kg dry weight) rose from 18. 1+/-3.2 to 110.6+/-14.0 and
      recovered to 53.3+/-12.3 in the control group. The corresponding Nai values for
      EIPA-treated hearts were 16. 2+/-2.4, 39.6+/-9.6 and 12.6+/-3.5, respectively. In
      control hearts [Ca]i (nM/l) rose from 332+/-42 to 1157+/-89 and recovered to
      842+/-55, whereas in EIPA-treated hearts the values were 255+/-32, 616+/-69 and
      298+/-34, respectively. EIPA also preserved cellular ATP during ischemia and
      reperfusion and diminished inorganic phosphate during reperfusion (P<0.05).
      Finally, EIPA treatment improved recovery of left ventricular developed pressure
      (68.2+/-8.9 v 16.2+/-3.6% of control) and limited myocardial injury as indicated
      by decreased total creatine kinase release during reperfusion (348+/-132 v 2432+/
      639 IU/g dry weight). Thus, as in adults, the results from newborn hearts are
      consistent with the hypothesis.

PMID- 9281442
TI  - Cloning and cellular distribution of a group II phospholipase A2 expressed in the
      heart.
AB  - Phospholipase A2 has been considered to play a role in physiological membrane
      turnover in cardiac tissue and in the degradation of membrane lipids under
      pathophysiological conditions, such as ischemia and reperfusion. We report the
      cloning of a cDNA encoding a member of the Ca2+-dependent, low molecular mass
      phospholipase A2 (PLA2) present in rat heart. The cDNA predicts a mature protein
      of 146 amino acid residues including a 21 amino acid sequence at the N-terminal
      end, which has the features characteristic of eukaryotic secretory signal
      peptides. The deduced amino acid sequence constitutes an enzyme of the group II
      class of PLA2s, and resembles PLA2s from other mammalian sources. A Northern blot
      analysis performed to determine the tissue distribution showed that rat ileum
      contains the largest amount of the PLA2 transcript among the tissues examined, a
      weaker signal was present in heart, spleen and soleus muscle, and no signal could
      be detected in EDL muscle, stomach, liver, kidney, brain and lung. Northern blot
      analysis and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques
      indicate the presence of this enzyme in neonatal and adult rat cardiomyocytes and
      in a cultured rat cardiac fibroblast-like cell line, but not in rat cardiac
      derived endothelial cell lines. Transcription levels of rat heart group II PLA2
      in isolated neonatal rat cardiomyocytes were found to increase after stimulating
      the cells with tumor necrosis factor-alpha (TNF-alpha) or the alpha1-adrenergic
      agonist phenylephrine.

PMID- 9281443
TI  - Null mutation in the desmin gene gives rise to a cardiomyopathy.
AB  - A null mutation in the desmin gene has been introduced into the germ line of
      mice. Such mice develop and reproduce normally proving that desmin is not needed
      either for the formation of the heart or the alignment of functioning myofibrils.
      However, cardiovascular lesions and a skeletal myopathy were observed in growing
      and adult mice. In the present study we have carried out a detailed analysis of
      these cardiac lesions. Homozygous mutant mice, which were confirmed to lack
      expression of desmin mRNA and desmin protein in the heart, were revealed by
      electron microscopy to contain degenerating cardiomyocytes as early as 5 days
      post-partum. At 10 days post-partum and onwards the degeneration of
      cardiomyocytes gave rise to areas with an accumulation of macrophages, fibrosis
      and calcification preferentially in the inter-ventricular septum and the free
      wall of the right ventricle. The localization of the lesions mainly to these
      sites suggested that it is not the work load and contractions per se which were
      the pathogenic events leading to the cardiomyopathy. It might be that stress
      related to lengthening of the myocytes occur more in the right ventricle than in
      the left. At the ultrastructural level changes in the intercalated discs,
      disruption of the sarcolemma and supercontraction of myofibrils seemed to be the
      key events leading to cardiomyocyte death. Thus, the intermediate filaments are
      required to maintain the basic integrity of cardiomyocytes and especially the
      link between the intermediate filaments and the sarcolemma appear more important
      than previously realized.

PMID- 9281444
TI  - Dexamethasone-induced up-regulation of adrenomedullin and atrial natriuretic
      peptide genes in cultured rat ventricular myocytes.
AB  - To determine whether adrenomedullin (AM), a novel 51-residue vasodilator peptide
      originally isolated from human pheochromocytoma, is expressed by the heart, and
      whether the expression of cardiac AM gene is regulated by glucocorticoids, the
      effect of dexamethasone (DEX) on the expression of protein and mRNA of AM and
      atrial natriuretic peptide (ANP) was tested in cultured ventricular myocytes
      prepared from the neonatal rats. Northern blot analysis of rat ventricular
      myocytes with cDNAs for rat AM and ANP as probes revealed distinct bands
      corresponding to the sizes of rat AM mRNA (1. 6 kb) and rat ANP mRNA (1 kb),
      respectively. Dexamethasone increased steady-state levels of both AM and ANP mRNA
      as well as secretion of both AM and ANP immunoreactivity in a time- and dose
      dependent manner. The stimulatory effects of dexamethasone were completely
      abolished by a glucocorticoid antagonist (RU38486) and a RNA synthesis inhibitor
      (actinomycin D). The approximate half-lives of basal and dexamethasone-induced AM
      mRNA were about 4 h, suggesting that dexamethasone-induced up-regulation of AM
      mRNA was unlikely due to its decreased degradation. These data suggest that
      glucocorticoids directly stimulate gene expression of AM as well as ANP in rat
      ventricular myocytes.

PMID- 9281445
TI  - Phosphorylation of connexin43 and the regulation of neonatal rat cardiac myocyte
      gap junctions.
AB  - The functional state of gap junctions and the state of phosphorylation of
      connexin43 (Cx43), the major gap junction protein in rat heart, were evaluated in
      primary cultures of neonatal rat cardiocytes. Functional coupling was greatly
      reduced after treatment with staurosporine (ST), a protein kinase inhibitor. The
      ST-induced reduction in cell coupling was reversed by activation of protein
      kinase C (PKC) with 12-O-tetradecanoylphorbol 13-acetate (TPA). The cellular
      distribution of Cx43, as detected by immunofluorescence, was not grossly affected
      by either ST alone or ST plus TPA. Although immunoblot analysis did not detect
      significant changes in the relative amounts of the unphosphorylated and
      individual phosphorylated forms of Cx43 after each treatment, the level of 32P
      incorporation into Cx43 of radiolabeled cells was significantly affected.
      Consistent with their known properties, treatment with ST reduced, and combined
      treatment with TPA and ST increased, the level of 32P-incorporation into Cx43.
      Two-dimensional tryptic phosphopeptide maps of 32P-labeled Cx43 indicated that a
      distinct subset of the phosphopeptides that are present under basal conditions
      were affected by ST or ST/TPA treatments, with TPA-induced phosphorylation
      occurring at the ST-sensitive sites. However, the ST/TPA-sensitive tryptic
      phosphopeptides did not comigrate with others that were derived from in vitro
      phosphorylation by PKC of a recombinant C-terminal Cx43 peptide (Cx43[243-382]).
      Although a PKC-dependent mechanism appears to be involved in the regulation of
      functional coupling between neonatal rat cardiocytes, PKC itself may not be the
      final mediator of Cx43 phosphorylation.

PMID- 9281447
TI  - High expression and activation of MAP kinase-activated protein kinase 2 in
      cardiac muscle cells.
AB  - Recently, three mammalian mitogen-activated protein (MAP) kinases, ERK, SAPK/JNK,
      and p38/HOG-1 have been identified, each with apparently unique signal
      transduction pathways. The p38 MAP kinase mediates an intracellular stress
      activated signaling pathway by regulating down-stream molecules, such as MAP
      kinase-activated protein (MAPKAP) kinase 2. To study the tissue specificity of
      MAPKAP kinase 2, mRNA blots containing multiple human tissues were hybridized
      with a specific oligonucleotide probe corresponding to human MAPKAP kinase 2. The
      Northern blot analysis revealed that two mRNA species of MAPKAP kinase 2, with
      sizes of 4.8 and 3.3 kb, were expressed in high levels in both human heart and
      skeletal muscle tissues. To better understand how MAPKAP kinase 2 is regulated in
      myocardium, cultured rat cardiac myoblast (H9c2) cells were stimulated with heat
      shock, H2O2-induced oxidative stress, or phorbol ester (PMA). Enzymatic activity
      of cellular MAPKAP kinase 2 in the cell lysates was evaluated using an in vitro
      kinase assay. Exposure of H9c2 cells to heat shock or oxidative stress induced a
      transient increase of cellular MAPKAP kinase 2 activity, which reached its peak
      level within 5 min. In contrast, stimulation of H9c2 cells with PMA, a potential
      myocardial hypertrophic factor, induced a sustained increase of cellular MAPKAP
      kinase 2 activity that was detectable for over 1 h. In addition, in vitro protein
      phosphorylation analysis with recombinant MAPKAP kinase 2 showed that small heat
      shock protein (hsp25) served as a major substrate molecule for the kinase in H9c2
      cells and the protein phosphorylation of cellular hsp25 was stimulated by H2O2
      induced oxidative stress or PMA treatment in intact H9c2 cells. Moreover,
      exposure of H9c2 cells to H2O2-induced oxidative stress or PMA rapidly activated
      cellular p38 MAP kinase as detected by the induced protein phosphorylation of the
      kinase. Taken together, these results strongly suggest that MAPKAP kinase 2 may
      be involved in stress-activated signal transduction in myocardium.

PMID- 9281448
TI  - Infarct size measurement by triphenyltetrazolium chloride staining versus in vivo
      injection of propidium iodide.
AB  - Infarct size delineation by triphenyltetrazolium chloride (TTC) staining is
      dependent on sufficient reperfusion. We therefore evaluated the possibility of
      using propidium iodide (PI), a reagent conventionally used in flow cytometry to
      fluorescently stain dead cells, for infarct size analysis after short periods of
      reperfusion. Forty-five rabbits were subjected to either 15 min, 2 h or 4.5 h of
      coronary artery occlusion without reperfusion, or to 15 min, 30 min and 2 h of
      coronary artery occlusion followed by 30 min, 1 h and 3 h of reperfusion. Fifteen
      min before terminating the experiment, PI was injected into the left atrium.
      Patent blue violet was used to delineate the area at risk. Following incubation
      in TTC, the area at risk was excised and cross sections obtained for
      microscopical infarct size quantification by PI fluorescence. PI fluorescence was
      absent after permanent occlusion and in control areas. Infarct sizes measured by
      TTC staining were significantly smaller after 1 h of reperfusion as compared to 3
      h of reperfusion (30 min occlusion: 1+/-1 v 34+/-9%; P<0.05; 2 h occlusion: 9+/-6
      v 47+/-8%; P<0.01). In contrast, infarct sizes determined by PI fluorescence
      reached values comparable to those measured by TTC staining or conventional
      histology after longer times of reperfusion already after 30 min of reperfusion
      (30 min occlusion: 35+/-16.5%; 2 h of occlusion: 61+/-8%). Therefore, after short
      times of reperfusion infarct size measurement by PI fluorescence is more reliable
      than by TTC staining.

PMID- 9281446
TI  - Angiotensin II-mediated growth and antigrowth effects in cultured neonatal rat
      cardiac myocytes and fibroblasts.
AB  - Angiotensin II (Ang II) stimulates cardiovascular growth and remodeling via AT1
      receptors. Recent experiments have shown that Ang II may also exert
      antiproliferative effects via AT2 receptors. We studied the effects of Ang II on
      protein and DNA content and synthesis rate in unstimulated and endothelin-1 (ET
      1)-stimulated neonatal rat cardiomyocytes and fibroblasts, isolated from 1-3-day
      old Wistar strain pups. Total protein and total DNA, as well as [3H]leucine and
      [3H]thymidine incorporation were measured following incubation with either
      vehicle, Ang II, ET-1 or Ang II+ET-1, both in the presence or absence of the AT1
      receptor blocker losartan or the AT2 receptor blocker PD123319. In myocytes, ET-1
      increased total protein (+38% relative to control) as well as [3H]leucine (+66%)
      and [3H]thymidine (+77%) incorporation. Ang II did not affect any of these
      parameters, nor did it influence the ET-1-induced responses. However, in the
      presence of PD123319 Ang II stimulated [3H]leucine (+24%) and [3H]thymidine
      (+30%) incorporation. In fibroblasts, ET-1 and Ang II did not significantly
      affect total DNA and [3H]thymidine incorporation. Ang II tended to increase total
      protein in these cells, an effect which was significant only in the presence of
      PD123319 (+17%). Ang II stimulated [3H]leucine incorporation (+24%) in
      fibroblasts. This effect was absent with losartan and enhanced in the presence of
      PD123319. These data demonstrate that AT1 receptor-mediated proliferative effects
      of Ang II in neonatal cardiac cells may become apparent only when its AT2
      receptor-mediated antigrowth effects are blocked. The net growth effect of Ang II
      therefore depends on the cellular AT1/AT2 receptor ratio. Ang II does not appear
      to interfere with ET-1-induced effects.

PMID- 9281449
TI  - Novel smooth muscle cell lines from transgenic mice harboring temperature
      sensitive SV40 large T-antigen gene. Temperature-dependent expression of smooth
      muscle myosin heavy chain-1 and calponin genes.
AB  - We have established novel vascular smooth muscle cell lines (SVS30 and SVS24
      cells) which retain the expression of specific markers for smooth muscle cells,
      such as alpha-actin, smooth muscle myosin heavy chain-1, and calponin, from
      transgenic mice harboring the temperature-sensitive SV40 large T-antigen gene.
      SVS cell lines showed temperature-dependent growth and the expression of SV40
      large T-antigen. Interestingly, protein and mRNA levels of smooth muscle myosin
      heavy chain-1 and calponin seen in culture at the non-permissive temperature (39
      degrees C) were higher than those at the permissive temperature (33 degrees C).
      These results suggest that SV40 large T-antigen affects the expression of smooth
      muscle-specific markers in SVS cell lines, and that some of the characters in SVS
      cell lines can be controlled by culture temperature. SVS cell lines should be
      quite valuable tools with which to study the regulation of phenotypic modulation
      of smooth muscle cells, and to identify smooth muscle specific transcription
      factors which involve the expression of smooth muscle myosin heavy chain-1 and
      calponin genes.

PMID- 9281450
TI  - Ischemic preconditioning and morphine-induced cardioprotection involve the delta
      (delta)-opioid receptor in the intact rat heart.
AB  - Several investigators have demonstrated that the opioid pathway is involved in
      tissue preservation during hypoxia or ischemia and that this protection is
      mediated via the delta (delta)-opioid receptor. Subsequently, we have shown that
      opioid receptors are involved in ischemic preconditioning (PC) in the rat heart
      and that morphine produces a cardioprotective effect; however, the class of
      opioid receptors involved in mediating these effects is still unknown. Therefore,
      the purpose of the present study was to test the hypothesis that ischemia- and
      morphine-induced cardioprotection are mediated via stimulation of the delta
      opioid receptor in the rat heart. Anesthetized, open-chest Wistar rats were
      subjected to one of six protocols. The control group was subjected to 30 min of
      occlusion and 2 h of reperfusion. Ischemic PC was elicited by three 5 min
      occlusion periods interspersed with 5 min of reperfusion. Morphine-induced
      cardioprotection was produced by three 5 min morphine infusions (100
      microg/kg/infusion, i.v.) interspersed with a 5-min drug-free period. To
      determine if the delta-opioid receptor has a role in ischemic PC and morphine
      induced cardioprotection, naltrindole (NTI), a selective delta-opioid receptor
      antagonist, was utilized. NTI (5 mg/kg, i.v.) was given 10 min prior to ischemic
      PC (NTI+PC) or morphine infusion (NTI+MOR). Also, NTI (5 mg/kg, i.v.) was given
      10 min before the 30 min occlusion period in untreated rats. Infarct size (IS) as
      a percent of the area at risk (AAR) was determined by 2,3,5-triphenyltetrazolium
      chloride staining. Ischemic PC and morphine infusions resulted in similar
      reductions in IS/AAR from 51+/-4 to 11+/-3 and 15+/-4% (*P<0.05), respectively.
      NTI completely abolished the cardioprotective effect induced by ischemia and
      morphine. The results of the present study suggests a role of delta;-opioid
      receptors in ischemic PC or morphine-induced myocardial protection in the rat.

PMID- 9281451
TI  - Calcium induced contracture stimulates Na,K-pump rate in isolated sheep cardiac
      Purkinje fibers.
AB  - By keeping intracellular Na+ (aiNa) low, the Na,K-pump can prevent Ca2+ overload
      of cardiomyocytes. We therefore examined whether Ca2+ stimulates Na,K-pump
      activity in sheep cardiac Purkinje fibers. By removing Ca2+, Mg2+ and K+, the
      fibers depolarized and aiNa rose to 70 mM. After addition of 6 mM Mg2+ and
      lowering extracellular Na2+ to 29 mM, 30mM Rb+ was added, and over 10-15 min aiNa
      recovered to 3-7 mM. Two load-recovery cycles were conducted in 10 fibers. During
      one of the cycles Ca2+ (0.1-1.0 mM) was added before Rb+, causing a contracture.
      During recovery aiNa fell faster during Ca2+ contracture than in control cycles.
      Between 30 and 20 mM the rates were -10.0+/-1.6 and -5.4+/-0.6 mM/min,
      respectively (P<0.05). In Ca2+-exposed fibers tension fell almost parallel with
      aiNa. Na, K-pump reactivation caused membrane potential (Vm) to hyperpolarize
      transiently to -70 mV. Ca2+ did not affect membrane conductance. For a given aiNa
      during reactivation, Vm was more negative during Ca2+ contracture and depolarized
      faster (P<0.05). Intracellular pH (pHi) fell from 7.11+/-0.05 to 6.92+/-0.08
      (n.s.) during control load-recovery cycles and was 6.83+/-0.14 at the end of the
      Ca2+ cycles. ATP content of the fibers did not change significantly through two
      complete load-recovery cycles, but creatine phosphate (CrP) fell by about 40%. By
      fitting the data to a model incorporating the Hill equation we show that during
      Ca2+-induced contracture maximum Na,K-pump rate (Vmax) was increased by about 40%
      and aiNa that causes 50% pump activation (k0.5) was lowered from 21. 2+/-1.6 to
      15.5+/-1.4 mM.

PMID- 9281452
TI  - Differential protein expression and subcellular distribution of TGFbeta1, beta2
      and beta3 in cardiomyocytes during pressure overload-induced hypertrophy.
AB  - The transforming growth factor beta (TGFbeta) superfamily plays an important role
      in the myocardial response to hypertrophy. We have investigated the protein
      expression of TGFbeta1, beta2 and beta3 in left ventricular tissue, and
      determined their subcellular distribution in myocytes by immunoblotting and
      immunocytochemistry during the development of left ventricular hypertrophy (LVH),
      using isoform specific antibodies to TGFbeta1, beta2 and beta3. LVH was produced
      in rats by aortic constriction (AC) and LV tissue was obtained at days (d)0, 1,
      3, 7, 14, 21 and 42 following operation. Compared with age matched sham-operated
      controls (SH), TGFbeta1 levels in LV tissue of AC rats increased significantly
      from d1-d14 (P<0.03) concomitant with the adaptive growth of LV tissue. In
      contrast, TGFbeta3 levels decreased in LV tissue of AC rats from d3 post
      operation (significant from d14-d42, P<0.03). No significant difference in
      TGFbeta2 levels were observed from SH and AC rats after operation. Antibodies to
      TGFbeta1 stained intercalated disks, sarcolemmal membranes and cytoplasm, but not
      nuclei, of cardiomyocytes on LV sections from untreated and SH rats. However, a
      trans-localisation of TGFbeta1 to the nuclei of cardiomyocytes was observed in AC
      hearts. Antibodies to TGFbeta3 stained T tubules, cytoplasm and the nuclei of
      cardiomyocytes from untreated and SH rats. However, by d7 post-AC operation,
      TGFbeta3 expression was lost rapidly from nuclei of cardiomyocytes followed by a
      reduction in total TGFbeta3 immunofluorescence in myocytes. Antibodies to
      TGFbeta2 stained sarcolemmal membranes of cardiomyocytes from both SH and AC rats
      without significant difference between groups. Thus, the differential pattern of
      protein expression and subcellular distribution of TGFbeta1, beta2 and beta3 in
      myocytes during the development of LVH suggests that these molecules play
      different roles in the response of cardiomyocytes to LVH.

PMID- 9281453
TI  - Cytoplasmic redox potential affects energetics and contractile reactivity of
      vascular smooth muscle.
AB  - Variations in the cytoplasmic redox potential (Eh) and NADH/NAD ratio as
      determined by the ratio of reduced to oxidized intracellular metabolite redox
      couples may affect mitochondrial energetics and alter the excitability and
      contractile reactivity of vascular smooth muscle. To test these hypotheses, the
      cytoplasmic redox state was experimentally manipulated by incubating porcine
      carotid artery strips in various substrates. The redox potentials of the
      metabolite couples [lactate]/[pyruvate]i and [glycerol 3
      phosphate]/[dihydroxyacetone phosphate]i varied linearly (r=0.945), indicating
      equilibrium between the two cytoplasmic redox systems and with cytoplasmic
      NADH/NAD. Incubation in physiological salt solution (PSS) containing 10 mm
      pyruvate ([lact]/[pyr]=0.6) increased O2 consumption approximately 45% and
      produced anaplerosis of the tricarboxylic acid (TCA cycle), whereas incubation
      with 10 mm lactate-PSS ([lact]/[pyr]i=47) was without effect. A hyperpolarizing
      dose of external KCl (10 mM) produced a decrease in resting tone of muscles
      incubated in either glucose-PSS (-0.8+/-0.8 g) or pyruvate-PSS (-2.1+/-0.8 g),
      but increased contraction in lactate-PSS (1.5+/-0.7 g) (n=12-18, P<0.05). The
      rate and magnitude of contraction with 80 mm KCl (depolarizing) was decreased in
      lactate-PSS (P=0.001). Slopes of KCl concentration-response curves indicated
      pyruvate>glucose>lactate (P<0.0001); EC50 in lactate (29. 1+/-1.0 mM) was less
      than that in either glucose (32.1+/-0.9 mm) or pyruvate (32.2+/-1.0 mM), P<0.03.
      The results are consistent with an effect of the cytoplasmic redox potential to
      influence the excitability of the smooth muscle and to affect mitochondrial
      energetics.

PMID- 9281455
TI  - Antibodies against stress proteins in sera of patients with dilated
      cardiomyopathy.
AB  - The pathogenesis of dilated cardiomyopathy (DCM) is as yet unknown. However, it
      is widely believed that autoimmune mechanisms contribute to the manifestations of
      the disease. In sera of patients with dilated cardiomyopathy, antibodies against
      different antigens, including heat shock protein (hsp) 60, were found. Antibodies
      against other stress proteins have not yet been reported. The aim of this study,
      therefore, was to screen sera of patients with DCM for the presence of antibodies
      against the major stress proteins. Lysate of stressed human endothelial cells was
      used as antigenic substrate in 1- and 2-dimensional immunoblot, since this cell
      type has recently been shown to express the major stress proteins. Antibodies
      against hsp60, hsp70, and heat shock cognate protein (hsc) 70 were detected in
      sera of patients with dilated cardiomyopathy as compared to healthy controls.
      Interestingly, antibodies against hsp70 and hsc70 were found in sera of patients
      younger than 30 years significantly more often than in older individuals. A
      correlation between the presence of antibodies against stress proteins and
      disease activity, clinical status, or histological findings was not detected.
      These findings support the view that DCM might be a consequence of an infectious
      disease, because stress proteins are immunodominant antigens in microbial agents
      and antibodies against stress proteins were detected in sera of patients with
      infectious diseases. Whether these antibodies are of pathogenetic significance or
      may be used as a disease marker will have to be elucidated in future experiments.

PMID- 9281454
TI  - Hypoxia regulates basal and induced DNA synthesis and collagen type I production
      in human cardiac fibroblasts: effects of transforming growth factor-beta1,
      thyroid hormone, angiotensin II and basic fibroblast growth factor.
AB  - Analysis of post-infarct ventricular remodeling consistently shows the
      accumulation of collagen in failing heart. The goal of this study was to gain
      insights into the underlying mechanisms of this event. We determined the effect
      of hypoxia, caused as the result of ischemia, on biological responses including
      cell viability, basal and growth factor-stimulated proliferative capacity and
      collagen type I production in cardiac fibroblasts obtained from adult human
      heart. The cell viability, as examined by light microscopy and analysis of DNA,
      did not change by hypoxia (2% oxygen). Basal level of protein synthesis, as
      determined by measuring the incorporation of 3H-leucine, decreased (30%, P<0.05)
      under hypoxia. Transforming growth factor-beta (TGF-beta1)- and thyroid hormone
      (T3)-induced increases in protein synthesis did not change under hypoxia. In
      contrast, basic fibroblast growth factor (bFGF)-stimulated protein synthesis
      enhanced significantly under hypoxia. Angiotensin II (Ang II)-treatment, which
      did not induce significant changes in protein synthesis under ambient conditions,
      led to moderate but significant increase under hypoxia. Basal level of DNA
      synthesis, as determined by measuring the incorporation of 3H-thymidine into DNA,
      decreased (32%, P<0.05) under hypoxia. The TGF-beta1-induced inhibition of DNA
      synthesis which was observed under ambient conditions was reversed [61% (P<0.005)
      increase under hypoxia]. Under ambient conditions, T3, Ang II and bFGF stimulated
      DNA synthesis and their effects were enhanced under hypoxia. Northern analysis
      showed a 46% (P<0.05) increase in the level of pro alpha1(l) collagen mRNA under
      hypoxia. The TGF-beta1-induced increase in the level of pro alpha1(l) collagen
      mRNA, under ambient conditions, was not observed under hypoxia. On the other
      hand, the T3-induced decrease in pro alpha1(l) collagen mRNA was reversed under
      hypoxia. Ang II- and bFGF-treatment of human cardiac fibroblasts did not cause
      detectable changes in the level of pro alpha1(l) collagen mRNA under ambient
      conditions or hypoxia. At the protein level, the amount of immunoreactive
      collagen type I, as determined by immunoslot blot analysis, was increased (33%,
      P<0.05) under hypoxia. Treatment of human cardiac fibroblasts with TGF-beta1 and
      T3 under ambient conditions led to diminished level of collagen type I. Under
      hypoxia, however, effect of both factors was reversed. The level of
      immunoreactive collagen type I in Ang II- and bFGF-treated cells, which was
      comparable to that in untreated cells under ambient conditions, remained
      unchanged under hypoxia. Together, these results provide evidence that hypoxia
      regulates growth, proliferative capacity and collagen type I production in human
      cardiac fibroblasts, and that although hypoxia alone may not be a stimulus for
      human cardiac fibroblast proliferation, it enhances growth factor-induced DNA
      synthesis in those cells. Furthermore, hypoxia by increasing the basal levels of
      collagen type I and by reversing the TGF-beta1- and T3-induced inhibition of
      collagen type I gene expression in human cardiac fibroblasts can enhance overall
      collagen type I production. Combinatorial effects of hypoxia on proliferation and
      collagen type I production in cardiac fibroblasts contribute to the post-infarct
      remodeling of the collagen matrix in failing human heart.

PMID- 9281456
TI  - Inhibition of glycogenolysis by a glucose analogue in the working rat heart.
AB  - The effects of BAY o 1248, an inhibitor of alpha-amylo-1, 6-glucosidase, on
      glycogenolysis and post-ischemic functional recovery were investigated in
      isolated perfused rat hearts. Working rat hearts were perfused during 30 min with
      11 mm glucose (controls) and, in some hearts, with 1 microM insulin or 5 mM
      lactate to increase their glycogen concentration. The hearts were then submitted
      to 10 min of no-flow ischemia and reperfused during 15 min with 11 mM glucose
      alone. Glycogen content was increased by 50% in hearts perfused with insulin or
      lactate. During ischemia, glycogen breakdown was similar in the control and
      lactate groups, but was abolished in the insulin-group. At reperfusion,
      functional recovery was improved in glycogen-loaded hearts compared to controls.
      When hearts were perfused with 1 mM BAY o 1248, added before ischemia,
      glycogenolysis was inhibited in the three groups and functional recovery was
      hampered in both the control and lactate groups. In the insulin group, however,
      the functional recovery was barely affected by BAY o 1248. We conclude that: (i)
      BAY o 1248 is an inhibitor of heart glycogen breakdown; (ii) the consequences of
      inhibition of ischemic glycogenolysis on post-ischemic functional recovery depend
      on the conditions; and (iii) the protective effect of insulin does not result
      from ischemic glycogenolysis.

PMID- 9281457
TI  - Expression and activities of cyclins and cyclin-dependent kinases in developing
      rat ventricular myocytes.
AB  - The molecular mechanisms responsible for the alterations in proliferative
      capacity of cardiac myocytes during development remain unknown; however, cell
      cycle dependent molecules may be involved. We have determined the expression of
      cyclins A, D1-3 and E, and cyclin-dependent kinases (CDKs) 2, 4, 5 and 6 and cdc2
      in freshly isolated rat cardiac myocytes from fetal (18 days gestation), neonatal
      (2 days post-natal) and adult animals by immunoblotting. Our results show a
      dramatic decrease in expression of these proteins during normal cardiac
      development, such that levels are highest in fetal myocytes but are significantly
      down-regulated in adult cells (P<0.05, in each case). We also have determined the
      in vitro kinase activities of cdc2, CDK2, CDK4, CDK5 and CDK6 immunocomplexes in
      fetal, neonatal and adult myocytes. There was a consistent and significant loss
      of cdc2, CDK2, CDK4 and CDK6 kinase activities in adult cardiac cell lysates (5.3
      , 10.6-, 1.5- and 1.9-fold decreases, respectively) when compared to neonatal
      samples (P<0.05); CDK5 activity showed a similar trend but failed to reach
      significance. In conclusion, our results show that the expression and activities
      of various positive regulators of the cell cycle are down-regulated significantly
      during development of the cardiac myocyte, concomitant with the loss of
      proliferative capacity in adult myocytes. Down-regulation of these proteins may
      be pivotal in the withdrawal of the cardiac myocyte from the cell cycle.

PMID- 9281458
TI  - Phorbol ester, but not ischemic preconditioning, activates protein kinase D in
      the rat heart.
AB  - The signal transduction pathways that mediate the cardioprotective effects of
      ischemic preconditioning remain unclear. Here we have determined the role of a
      novel kinase, protein kinase D (PKD), in mediating preconditioning in the rat
      heart. Isolated rat hearts (n=6/group) were subjected to either: (i) 36 min
      aerobic perfusion (control); (ii) 20 min aerobic perfusion plus 3 min no-flow
      ischemia, 3 min reperfusion, 5 min no-flow ischemia, 5 min reperfusion (ischemic
      preconditioning); (iii) 20 min aerobic perfusion plus 200 nmol/l phorbol 12
      myristate 13-acetate (PMA) given as a substitute for ischemic preconditioning.
      The left ventricle then was excised, homogenized and PKD immunoprecipitated from
      the homogenate. Activity of the purified kinase was determined following
      bincubation with [gamma32P]-ATP+/-syntide-2, a substrate for PKD. Significant PKD
      autophosphorylation and syntide-2 phosphorylation occurred in PMA-treated hearts,
      but not in control or preconditioned hearts. Additional studies confirmed that
      recovery of LVDP was greater and initiation of ischemic contracture and time-to
      peak contracture were less, in ischemic preconditioned hearts compared with
      controls (P<0.05). Our results suggest that the early events that mediate
      ischemic preconditioning in the rat heart occur via a PKD-independent mechanism.

PMID- 9281459
TI  - Preconditioning of isolated rabbit cardiomyocytes: no evident separation of
      induction, memory and protection.
AB  - Cardiomyocytes isolated from rabbit hearts were preconditioned in vitro by 10 min
      of ischemia or treatment with 100 microM adenosine. Protection was assessed as
      average integrated mortality following osmotic swelling and determination of
      viability by trypan blue exclusion over 60-180 min ischemia. Repetitive sub
      maximal stimulations with 1 microM adenosine amplified the protective response.
      Treatment with adenosine only at the onset of prolonged ischemia afforded a dose
      dependent protection. The PKC inhibitor calphostin C (500 nm) blocked
      preconditioning and, when added during ischemic incubation of non-preconditioned
      cells, significantly increased injury. The memory of adenosine-induced
      preconditioning decayed over a 60 min post-incubation period. Light activation of
      calphostin C initially added to preconditioned ischemic cells in the dark
      indicated that a 10 min period of PKC activity at the onset of ischemia affords
      full protection. The reversible PKC inhibitors chelerythrine (5 microM) or
      staurosporine (100 nM) added only to bracket induction of ischemia, reduced but
      did not abolish protection. Protection was abolished when either drug was present
      during induction and a subsequent 30 min post-incubation period. Staurosporine
      included during initiation and post-incubation but washed out in the final 5 min
      of post-incubation allowed significant protection to occur. It is concluded that
      a single adenosine receptor-stimulation induces protection as it preconditions,
      and PKC activity appears to be required for both induction and protection. Memory
      may reside in post-receptor amplification of an initial protective response.

PMID- 9281460
TI  - Angiotensin II receptor type 1 mRNA is upregulated in atria of patients with end
      stage heart failure.
AB  - There is increasing evidence that pathological changes in the myocardium during
      chronic heart failure (CHF) are partly regulated through the activation of the
      renin-angiotensin system (RAS), an effect mediated by the angiotensin II type 1
      receptor (AT1R). We examined the expression of cardiac AT1R mRNA in normal
      (atria, n=7; ventricle, n=3) and end-stage CHF human hearts (atria, n=8;
      ventricle, n=14). Tissue was snap-frozen immediately after explantation during
      orthotopic cardiac transplantation; control specimens were obtained from healthy
      donor hearts rejected for technical reasons. Northern blots of purified total
      mRNA from each tissue were hybridized with a random primed radiolabeled probe for
      the coding sequence of AT1R. Stringent conditions were used for both
      hybridization (5X SSC, 65 degrees C) and washing (0.5X SSC, 0.1% SDS, 65 degrees
      C) of the membrane. Left and right atrial tissue showed low levels of AT1R mRNA
      expression in the controls, with statistically significant upregulation of
      expression in tissue from pathological hearts; CHF atria 1.28+/-0.86 optical
      density (OD) units, control atria 0.56+/-0.31 OD units, P=0.05 (mean+/-s.d.).
      There were undetectable levels in ventricles from either control (2/2) or dilated
      hearts (7/7). The results were independent of the etiology of the heart failure
      and suggest that increased levels of atrial AT1R mRNA may occur in response to
      elevated atrial pressures in heart failure.

PMID- 9281461
TI  - Monophosphoryl lipid A protects adult rat cardiac myocytes with induction of the
      72-kD heat shock protein: a cellular model of pharmacologic preconditioning.
AB  - We examined the in vitro preconditioning effect of non-toxic derivative of
      endotoxin, monophosphoryl lipid A (MLA) in adult rat cardiac myocytes. Cultured 5
      7-day-old myocytes were preconditioned for 4 h by treatment with 200 ng/ml MLA.
      Twenty h later, cells were subjected to simulated ischemia by incubation in 0.75
      mm sodium hydrosulfite, 12 mM KCl, 20 mM dl-lactic acid and 10 mM 2-deoxy-D
      glucose (pH 6.5) for 2 h. MLA caused a significant reduction in the levels of LDH
      from 286+/-8 units/l in controls to 165+/-5 units/l (mean+/-s.e.m.; P<0.0001).
      Similarly, CK significantly decreased from 104+/-3.1 in controls to 85+/-1.4 U/l
      (P<0.001). Western blot analysis indicated a significant accumulation of 72 kD
      heat shock protein in MLA treated as compared to control cells. No changes in 27,
      32, and 90 kD heat shock proteins were discernible in the MLA treated group.
      These data suggest a significant "anti-ischemic" effect of MLA in myocytes that
      is accompanied by induction of 72 kD heat shock protein.

PMID- 9281464
TI  - In vivo diagnostic procedures: skin testing, nasal provocation, and bronchial
      provocation.
AB  - In vivo challenge procedures can be very useful in the analysis of allergic
      symptoms. Skin testing has a high degree of sensitivity and specificity for
      determining antigens that cause allergic disease. However, positive skin tests do
      not necessarily indicate that a specific allergen causes symptoms specific for a
      certain organ. Nasal and whole lung provocation testing can help define relevant
      allergens that cause rhinitis or asthma symptoms. These tests are safe when
      performed properly under close medical supervision and have predictive values
      that make them useful diagnostic tools.

PMID- 9281463
TI  - Allergen source materials and quality control of allergenic extracts.
AB  - Allergen extracts are prepared from a wide variety of source materials including
      pollens, fungi, arthropods, animal danders, foods, and dusts. The composition of
      allergen extracts can vary depending on the allergen source, manufacturing
      process, and storage conditions. Allergen-specific immunoglobulin E (IgE) assays
      and skin tests employ a variety of allergen-containing reagents that confer
      specificity on the test. Given that the allergen source materials are
      heterogenous mixtures of proteins, glycoproteins, carbohydrates, and other
      substances that are not allergenic, it is not unexpected that variability exists
      between test results obtained with different allergen-containing reagents.
      Variability within a single manufacturer's allergen product can be controlled by
      using reproducible extraction and processing procedures, single large lots of
      allergen source materials, and solid-phase supports. These controls do not,
      however, ensure the consistency of products between manufacturers or laboratories
      because allergen source materials, manufacturing procedures, and acceptance
      criteria for allergen reagents may vary.

PMID- 9281465
TI  - Laboratory analyses in the diagnosis of human allergic disease.
AB  - The clinical immunology laboratory provides support to the allergist in the
      diagnosis and management of human allergic diseases. Following a clinical
      history, the detection of allergen-specific immunoglobulin E (IgE) in serum can
      be useful in the definitive diagnosis of an IgE antibody-mediated
      hypersensitivity. Total serum IgE, the multiallergen screen, and mast cell
      tryptase are less commonly measured analytes in the work-up of the allergic
      patient. More recently, the clinical laboratory has employed monoclonal antibody
      based-enzyme immunoassays to quantify dust mite, cat, dog, and cockroach
      indicator aeroallergen levels in indoor home and work environments. Levels of
      allergenic proteins in environmental and medical/consumer products are measured
      by other assays such as the competitive inhibition radioallergosorbent test.
      Methods of quantification, internal quality control, and external proficiency
      testing programs are emphasized in this report.

PMID- 9281466
TI  - Diagnostic allergy laboratory external proficiency testing in Europe.
AB  - As with all diagnostic laboratory testing, some form of external proficiency
      testing is required both for the laboratory undertaking the testing and for the
      safety of the requesting clinician and his patient. Allergen Specific
      immunoglobulin E antibody testing in serum can produce different results
      depending on the method. Originally External Quality Assessment schemes in Europe
      were run on a National basis but 5 years ago a cooperation scheme was adopted
      whereby each National scheme adopted common serum pools for distribution, common
      distribution dates, and a common report format. The EUROEQAS circulates a common
      report to each of the participants throughout Europe. This article describes the
      organization of such a scheme and the results produced over the past 12 months.

PMID- 9281468
TI  - Environmental allergen analyses.
AB  - Environmental specimens (dust) from indoor home, school, and work-place
      environments can be evaluated for the content of aeroallergens produced by dust
      mite, cat, dog, cockroach, and molds, as a means of determining exposure risk and
      facilitating avoidance therapy. This article examines the variables that
      influence the levels of these allergens in indoor environments, methods for
      sampling, clinical laboratory assays used for testing, and interpretation of
      aeroallergen results for making decisions about remediation.

PMID- 9281467
TI  - Markers of mast cell degranulation.
AB  - Mast cells are the primary effector cells of immediate hypersensitivity reactions
      in humans. Upon mast cell activation both preformed and newly synthesized
      mediators are secreted. Histamine can be measured by fluorometric assays,
      radioenzymatic assays, and immunoassays. These methods have been applied to
      plasma and urine to detect histamine that had been released in vivo and to
      release histamine in vitro from basophils and mast cells. Another mast cell
      constituent is tryptase, which is a more selective marker of mast cells, because
      negligible amounts are found in basophils. beta-Tryptase is stored in secretory
      granules and is actively released when mast cells degranulate. alpha-Protryptase
      remains in the proenzyme form and is constitutively released from mast cells, and
      consequently its level in serum reflects total numbers of mast cells. alpha
      Protryptase levels are elevated in serum at baseline in subjects with systemic
      mastocytosis, whereas beta-tryptase is elevated in serum from subjects with
      systemic anaphylaxis. These markers serve as precise clinical indicators of the
      involvement of mast cells in human disease.

PMID- 9281469
TI  - Studies of cell adhesion and flow cytometric analyses of degranulation, surface
      phenotype, and viability using human eosinophils, basophils, and mast cells.
AB  - Products derived from eosinophils, basophils, and mast cells are considered
      critical to the development of allergic diseases. Studies of the selective
      recruitment, accumulation, and/or activation of these cells during human allergic
      inflammatory reactions in vitro and in vivo have been facilitated by a wide
      variety of methods. Some have been developed to identify and isolate these cells
      from a variety of sites, including blood, airway secretions, and surgical or
      autopsy tissues. Once enriched in purity, assays of cell adhesion to endothelium,
      epithelium, matrix proteins, and purified, immobilized counterligands for
      integrins, selectins, or immunoglobulin gene superfamily structures can be
      performed in vitro under both static and flow conditions. Techniques involving
      flow cytometry, utilizing characteristics of cellular light scatter and
      immunofluorescence, have permitted the elucidation of cell surface phenotype and
      have aided in quantification of cellular degranulation and viability. These
      approaches have yielded new information on the function of human eosinophils,
      basophils, and mast cells and have suggested unique cell-specific pathways of
      cell recruitment, activation, and survival that may contribute to the
      pathogenesis of allergic diseases.

PMID- 9281470
TI  - Immunologic investigations of T-cell regulation of human IgE antibody secretion
      and allergic responses.
AB  - The pathophysiology of allergic disease is multifactorial, involving an intricate
      network of interactions among cells, mediators, and cytokines. Substantial
      progress has been made in defining the role of antigen-specific T cells and
      cytokines in the regulation of immunoglobulin E (IgE) synthesis and the atopic
      diseases. The development of antigen-specific T-cell lines and clones has
      facilitated efforts to characterize human T-cell subsets and their cytokine
      repertoires. Molecular methods currently available include techniques for the
      quantitative analysis of cytokine gene expression and secretion from activated T
      cells ex vivo as well as in tissues. The availability of these newly developed
      techniques has become essential to the investigation of the pharmacologic
      regulation of T cells and cytokines both in vitro and in vivo. Future
      investigations will contribute to our understanding of the differential
      regulation of T-cell subsets and their relationships to allergic diseases,
      ultimately leading to a better understanding of the molecular pathogenesis of
      allergic diseases and the design of more effective therapeutic interventions.

PMID- 9281471
TI  - Establishment of a Streptococcus pneumoniae nasopharyngeal colonization model in
      adult mice.
AB  - Human nasopharyngeal carriage of Streptococcus pneumoniae constitutes the major
      natural reservoir of pneumococci and is thought to be the prelude to virtually
      all pneumococcal disease. If carriage could be greatly reduced, pneumococcal
      transmission and disease could be largely eliminated. To facilitate the studies
      of mechanisms important in carriage and to identify immunogens that can elicit
      protection against carriage, we characterized an adult mouse model of
      nasopharyngeal carriage. Non-anaesthetized mice were inoculated intranasally with
      pneumococci in 10 microl of fluid. Nasopharyngeal carriage was observed with
      strains of capsular types 3, 4, 6A, 6B, 14, 19, and 23. Carriage was stable over
      time, and the numbers of pneumococci carried were relatively independent of
      inoculation dose; findings which indicate that the recovery of pneumococci from 1
      day to 2 weeks post inoculation was dependent on colonization, rather than just
      temporary contamination. To ensure carriage in the largest percentage of mice,
      without causing sepsis or death, inoculations of 10(7) colony forming units (cfu)
      should be used. In this model, carriage was generally observed without
      concomitant bacteremia or sepsis and carriage was observed even with strains that
      were avirulent when injected i.v. The model should be useful for the
      identification of protection-eliciting antigens, since intranasal immunization
      with heat-killed pneumococci or lysates of pneumococci protected against
      carriage.

PMID- 9281472
TI  - Lipopolysaccharide heterogeneity and escape mechanisms of Neisseria meningitidis:
      possible consequences for vaccine development.
AB  - We wanted to compare the potential protective capacity of antibodies to
      meningococcal lipopolysaccharides (LPS). The frequency of occurrence and degree
      of expression of the epitopes recognized by murine monoclonal antibodies (MAbs)
      to immunotypes L3,7,9 (9-2-L379) and L8 (2-1-L8) and to the LPS inner core (216
      Lc and 217-Lc), were determined among 77 consecutive Norwegian meningococcal
      patient isolates from 1995. The immunotype L3,7,9 was strongly expressed by 95%
      of the isolates, whereas L8 was weakly to moderately expressed by 9%. The inner
      core epitopes, were widely distributed among the serogroup B organisms, but were
      proved weakly expressed. The bactericidal activity of the four MAbs to various
      selected strains, was found to correlate positively with the quantity of the LPS
      epitopes recognized by these four MAbs in the bacteria. When tested in the serum
      bactericidal assay (SBA), often a few percent of the colonies of the inocula
      survived high concentrations of the MAbs. The results indicate that escape from
      the bactericidal action could be achieved through: (i) selection of variants not
      expressing the LPS-epitope of the actual MAb, (ii) a relative reduction in the
      density of the LPS-epitope achieved by dilution with another LPS structure or
      (iii) other factors, not yet understood. In conclusion, antibodies to the L3,7,9
      epitope seem to be of importance for protection, whereas antibodies to the
      epitopes of the LPS inner core or immunotype L8, are not likely to offer
      protection alone. However, in order to prevent escape through alteration of the
      LPS pattern of the microbes, various LPS structures should probably be present in
      the OMV vaccine.

PMID- 9281473
TI  - Adherence of non-typeable Haemophilus influenzae promotes reorganization of the
      actin cytoskeleton in human or chinchilla epithelial cells in vitro.
AB  - Non-typeable Haemophilus influenzae (NTHi) are opportunistic mucosal pathogens
      which adhere to epithelial cells via a variety of non-specific and specific
      interactions. Several adhesins have been identified and while the complimentary
      receptor(s) for each of these adhesins has not yet been fully characterized, it
      is widely accepted that adherence is an absolute prerequisite for disease.
      Several reports have indicated that NTHi can also be internalized and reside
      intracellularly. For this to occur, NTHi must be taken up by mucosal epithelial
      cells lining the respiratory tract. We have noted, by TEM, that adherent NTHi
      overlie an electron dense area in the cell membrane of human epithelial cells
      which is associated with a localized complex assembly of cytoskeletal fibers in
      the eukaryotic cytoplasm. We thus examined the potential involvement of
      cytoskeletal actin in this phenomenon via FITC-phalloidin labeling of respiratory
      tract epithelial cells which had been incubated with several clinical isolates of
      NTHi. Strong punctate fluorescence was coincident with adherent NTHi to both
      human oropharyngeal and chinchilla middle ear epithelial cells. This reactivity
      was similar to the discrete fluorescent spots observed with enteropathogenic
      Escherichia coli which were adhered to HeLa cells. In contrast, none of the NTHi
      isolates tested induced actin polymerization in cells of endothelial origin.
      While the exact mechanisms involved are yet to be elucidated, our data indicated
      that actin nucleation was coincident with NTHi adherence.

PMID- 9281474
TI  - Expression of an F1/V fusion protein in attenuated Salmonella typhimurium and
      protection of mice against plague.
AB  - A novel approach to making fusions of F1 and V antigens, which may be
      incorporated into a live recombinant vaccine for plague, was developed. The
      nucleotide sequences encoding Yersinia pestis V antigen (lcrV) and the mature
      form of F1 antigen (caf1) were amplified by PCR with primers which included
      tails. At the 3' end of caf1 and the 5' end of lcrV, the tails encoded one of
      three six- or eight-amino acid linkers or their complementary sequences. The DNA
      overlap in each linker region was used to prime a second PCR to generate three
      F1/V fusions, which were cloned into pUC18. The resulting plasmids expressed
      fusion proteins consisting of F1 and V antigens, separated by the linkers Gly-Ser
      Ile-Glu-Gly-Arg, Ser-Ala-Pro-Gly-Thr-Pro or Ser-Ala-Pro-Gly-Thr-Pro-Ser-Arg. As
      shown by Western blotting of bacterial cell lysates with anti-V and anti-F1 sera,
      the level of expression and degree of degradation of the three fusion proteins
      was similar. To investigate the immunogenicity of F1/V, one of the plasmids,
      placFV6 which encoded the Gly-Ser-Ile-Glu-Gly-Arg linker, was electroporated into
      the attenuated Salmonella typhimurium strain SL3261 (aroA). Mice receiving two
      intravenous doses of 5 x 10(6) cfu SL3261/placFV6 developed serum anti-V and anti
      F1 IgG titres, with similar IgG1:IgG2a isotype ratios, and T cell responses
      specific for V and F1 antigens. Six weeks after vaccination, mice were challenged
      subcutaneously with 7.4 x 10(2) or 7.4 x 10(4) LD50s of Y. pestis strain GB, and
      a significant degree of protection was demonstrated. These results demonstrate
      the potential of co-expressing Y. pestis antigens as fusion proteins to develop a
      live recombinant vaccine against plague.

PMID- 9281476
TI  - A comparison of the experimental and ab initio values of the 17O NMR chemical
      shifts in the carbonyl group.
AB  - New experimental and theoretical results are presented for the NMR shielding of
      oxygen in the carbonyl group. The experimental values clearly demonstrate that
      the solvent effects are very significant. The new results for the chemical shifts
      are in better agreement than the previous literature data with the corresponding
      ab initio values calculated for isolated molecules.

PMID- 9281475
TI  - Pathogenicity of Serpulina hyodysenteriae: in vivo induction of tumor necrosis
      factor and interleukin-6 by a serpulinal butanol/water extract (endotoxin).
AB  - Lipopolysaccharide (LPS) of Gram-negative bacteria is a classic inducer of
      inflammatory cytokines. In the present experiments, LPS-like (phenol/water
      extract) or endotoxin-like (butanol/water extract) preparations from Serpulina
      hyodysenteriae were examined for their ability to induce serum tumor necrosis
      factor (TNF) or interleukin (IL)-6 bioactivity in mice and swine. Serpulina
      hyodysenteriae endotoxin (butanol/water extract) elicited increased serum TNF
      activity in mice, although serpulinal endotoxin was at least 10 times less potent
      than the LPS preparations of E. coli or S. typhimurium on a weight basis for
      induction of TNF bioactivity. S. hyodysenteriae LPS induced lower levels of serum
      TNF in mice than S. hyodysenteriae endotoxin. In contrast, pigs injected with S.
      hyodysenteriae endotoxin demonstrated no increase in serum TNF activity. However,
      an induction of IL-6 bioactivity was observed in serum samples from pigs injected
      with serpulinal endotoxin. In pigs, the serpulinal preparations were five times
      less potent (on a weight basis) than E. coli or S. typhimurium LPS for induction
      of IL-6 bioactivity. These data indicate that serpulinal endotoxin, although less
      bioactive than E. coli or S. typhimurium LPS, is nonetheless capable of inducing
      the in vivo production of specific pro-inflammatory cytokines.

PMID- 9281477
TI  - Comparative studies of phase-cycling schemes for multiple pi-pulse sequences.
AB  - Recently, a new phase cycling scheme was introduced by this laboratory for use in
      biological solid-state NMR experiments involving multiple pi-pulses with
      characteristics that suggested it may enhance the sensitivity of these kind of
      experiments (Y. Li and J. N. S. Evans, 1995, Chem. Phys. Lett. 241, 79 and
      Erratum, 1995, ibid. 246, 527; Y. Li and J. N. S. Evans, 1996, J. Magn. Reson. B
      111, 296). The new sequence followed the supercycled concept proposed a decade
      ago for heteronuclear decoupling experiments. In this paper, more detailed
      experiments demonstrate that the claim of enhanced sensitivity was unfounded, and
      in fact the supercycle proposed differs little from the established XY-8 and XY
      16 based supercycles.

PMID- 9281478
TI  - REDOR dephasing by multiple spins in the presence of molecular motion.
AB  - Closed-form, numerical algorithms are presented for calculating REDOR dephasing
      for three general cases: (i) collections of isolated I-S spin pairs; (ii) many S
      spins coupled to an I spin; and (iii) an I-S spin pair in relative motion. For
      the case when more than one S spin is dipolar coupled to an I spin, the
      calculation assumes that the S-S homonuclear interaction does not affect REDOR
      dephasing. Full numerical simulations show that this assumption is true if the S
      spin lineshapes are inhomogeneously broadened, the S-spin chemical shifts are far
      from rotational resonance, and a version of REDOR is used which minimizes the
      number of S-spin pi pulses. For the rapidly rotating -CF3 group of
      poly(trifluoroethyl methacrylate), the formalisms of (ii) and (iii) are combined
      to calculate the dephasing. The experimentally measured dephasing matches theory
      when the wiggling motion of the -OCH2CF3 moiety of the polymer is taken into
      account.

PMID- 9281479
TI  - Multifrequency two-dimensional Fourier transform ESR: an X/Ku-band spectrometer.
AB  - A two-dimensional Fourier Transform ESR (2D FT ESR) spectrometer operating at
      9.25 and 17.35 GHz is described. The Ku-band bridge uses an efficient heterodyne
      technique wherein 9.25 GHz is the intermediate frequency. At Ku-band the
      sensitivity is increased by almost an order of magnitude. One may routinely
      collect a full 2D ELDOR spectrum in less than 20 min for a sample containing 0.5
      5 nmol of nitroxide spin-probe in the slow-motional regime. Broad spectral
      coverage at Ku-band is obtained by use of a bridged loop-gap resonator (BLGR) and
      of a dielectric ring resonator (DR). It is shown that an even more uniform
      spectral excitation is obtained by using shorter microwave pulses of about 3 ns
      duration. The dead-time at Ku-band is just 30-40 ns, yielding an improved SNR in
      2D ELDOR spectra of nitroxide spin-probes with T2 as short as 20-30 ns. A
      comparison of 2D ELDOR spectra obtained at 9.25 and 17. 35 GHz for spin-labeled
      phospholipid probes (16PC) in 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG)
      membrane vesicles showed that both spectra could be satisfactorily simulated
      using the same set of model parameters even though they are markedly different in
      appearance. The improved sensitivity and shorter dead-time at Ku-band made it
      possible to obtain orientation-dependent 2D ELDOR spectra of the Cholestane (CSL)
      spin-probe in macroscopically aligned lipid bilayers of egg yolk PC using samples
      containing only 1 mg of lipid and just 5 nmol of spin-probe.

PMID- 9281480
TI  - Analysis of spin diffusion and cross correlation on the net nuclear Overhauser
      effect in NMR.
AB  - The effect of dipole-dipole cross correlations on the net nuclear Overhauser
      effect (NOE) has been analyzed here for realistic systems by extending the three
      spin calculations to four and five spins in order to account for additional cross
      correlations and spin diffusion. These have been compared with the addition of
      leakage terms to the three-spin system. The additional spins enhance cross
      correlation effects on one hand but on the other act as supplementary relaxation
      pathways for the magnetization to diffuse. This analysis shows that for a linear
      array of spins in the long-correlation limit, dipole-dipole cross correlations
      increase net NOE, while spin diffusion decreases it, and that the cumulative
      effect is a reduced effect of cross correlations. In other geometries and
      correlation limits, the effect of cross correlations on net NOE is generally
      small.

PMID- 9281481
TI  - Modeling NMR lineshapes using logspline density functions.
AB  - Distortions in the FID and spin echo due to magnetic field inhomogeneity are
      proved to have a representation as the characteristic function of some
      probability distribution. In the special case that the distribution is Cauchy,
      the model reduces to the conventional Lorentzian model. A more general and
      flexible representation is presented using the Fourier transform of a logspline
      density. An algorithm for fitting the model is described, the performance of the
      model and algorithm is investigated in applications to real and simulated data
      sets, and the logspline approach is compared to a previous Hermitian spline
      approach and to the Lorentzian model. The logspline model is more parsimonious
      than the Hermitian spline model, provides a better fit to real data, and is much
      less biased than the Lorentzian model.

PMID- 9281482
TI  - Model-free approach beyond the borders of its applicability.
AB  - Model calculations presented in this article show that commonly used methodology
      of 15N relaxation data analysis completely fails in detecting nanosecond time
      scale motions if the major part of the molecule is involved in these motions. New
      criteria are introduced for the detection of such cases, based on the dependence
      of the apparent overall correlation time, derived from the T1/T2 ratio, on the
      spectrometer frequency. Correctly estimating the overall rotation correlation
      time tauR was shown to play the key role in model-free data analysis. It is
      found, however, that in cases of slow internal motions with characteristic times
      of more than 3-4 ns, the effective tauR provided by the T1/T2 ratio for
      individual amide nitrogens can be used for the characterization of the fast
      picosecond internal dynamics.

PMID- 9281483
TI  - Theory of multiple NMR spin echoes of HD impurities in solid para-H2.
AB  - The theory of the formation of NMR multiple echoes for isotopic impurities (HD)
      in solid para-H2 has been developed for the case of weak quantum tunneling of the
      impurities. The results show that even for low tunneling rates (100-1000 Hz), NMR
      multiple echoes can be observed for experimentally accessible nuclear spin
      polarizations and can be used to provide an independent test for the existence of
      tunneling in the solid hydrogens.

PMID- 9281484
TI  - Magnetic equivalence between nuclei of spin greater than 1/2 in presence of
      relaxation.
AB  - Both formal reasoning and numerical calculations of spectral lineshape functions
      confirm that magnetic equivalence between nuclei of spin greater than (1/2) is
      generally broken in presence of relaxation. This results in a dependence of the
      lineshape functions on the values of J-couplings between the nuclei that would be
      equivalent in absence of relaxation. Effects of this sort may be of practical
      importance for systems AnX, where the A nuclei are relaxed by quadrupolar
      interactions which are highly cross-correlated at different A sites.

PMID- 9281485
TI  - Selective homonuclear polarization transfer in the tilted rotating frame under
      magic angle spinning in solids.
AB  - An application of the R2TR method (1995, Chem. Phys. Lett. 232, 424) to selective
      homonuclear polarization transfer under magic angle spinning is proposed. It is
      shown that, for a spinning speed fast enough to remove the maximum homonuclear
      dipolar coupling constant omegaD involved, the flip-flop and flop-flop mechanisms
      are suitable for recoupling the spins with a chemical shift difference larger
      than omegaD and a difference comparable to or smaller than omegaD, respectively.
      It is also shown that, for fast polarization transfer, the off-resonance
      frequencies should be much higher than the RF intensity in the flip-flop
      condition, while for the flop-flop condition, the off-resonance frequencies
      should be much lower than the RF intensity. Some one- and two-dimensional
      experiments are proposed by utilizing the capability of the R2TR method to
      abruptly switch on and off the recoupling condition, and are demonstrated for
      triply 13C-enriched l-alanine. The mixing time required for population transfer
      was found to be ca. 0.5 ms for the methine and methyl 13C spins separated by 1.5
      A and ca. 5 ms for the methyl and the carboxyl carbons separated by 2.5 A. The
      experimental results and theoretical simulations show that selective polarization
      transfer is achieved when the difference in the isotropic chemical shifts between
      the relevant pair of spins and a neighboring spin is more than 1000 Hz.

PMID- 9281486
TI  - Multiple nonlinear stimulated echoes.
AB  - Three-pulse sequences in the presence of magnetic field gradients at high
      magnetic fields produce multiple nonlinear stimulated echoes (NOSE) at times
      ntau1 after the third pulse, where n is an integer and tau1 the interval between
      the first two pulses. These phenomena are due to the demagnetizing field produced
      by the spatial modulation of the nuclear magnetization arising in the sample
      after the first two pulses. The theory is presented and compared with
      experiments. The dependence of the NOSE amplitudes on the flip angles and on the
      pulse intervals is described. Implications for multidimensional NMR experiments
      based on sequences of three or more pulses in the presence of field gradients are
      discussed.

PMID- 9281487
TI  - Fresh spins for NMR signal enhancement through programmed sample translation
      cycles.

PMID- 9281488
TI  - Fast automatic adjustment of on-axis shims for high-resolution NMR.
AB  - A one-dimensional approach for fast, robust, automatic adjustment of on-axis
      shims on high-resolution NMR spectrometers based on polynomial fitting of field
      inhomogeneity is described. Spherical harmonic and nonspherical harmonic terms of
      the field distribution of shim coils are precalibrated as polynomial coefficients
      by successively changing shim settings. This method greatly simplifies the shim
      precalibration and optimization procedures and is readily to be extended to three
      dimensions to include off-axis shims.

PMID- 9281489
TI  - Compact MRI magnet design by stochastic optimization.

PMID- 9281490
TI  - Influence of proton chemical-shift anisotropy on magic-angle spinning spectra of
      hydrate crystals.
AB  - It is shown that the proton chemical-shift anisotropy of hydrate crystals affect
      dipolar powder pattern at 7.0 T. This may be clearly observed via an asymmetric
      envelope of dipolar spinning sidebands in magic-angle spinning proton spectra.

PMID- 9281491
TI  - Requirement of a limited segment of the sog gene for plasmid R64 conjugation.
AB  - The sog gene of the IncI1 plasmid R64 was sequenced and characterized. The sog
      gene was shown to express two acidic proteins, SogL and SogS, with 1255 and 844
      amino acid residues, respectively. The SogS protein was expressed by
      translational reinitiation within the SogL reading frame. Analysis of dnaG
      suppression activity using the Escherichia coli dnaG strain indicated that the
      domain for this activity was located within the N-terminal one-third segment of
      the SogL protein. A Deltasog mutation was constructed by replacing most of the
      sog coding sequence with a DNA fragment encoding a tetracycline resistance gene.
      Introduction of the Deltasog mutation into an R64 derivative resulted in
      approximately a 50-fold reduction in transfer frequency. It was observed that
      only a limited portion of the SogL or SogS protein corresponding to an internal
      0.94-kb EcoRV-SnaBI segment of the sog gene was required for the conjugal
      transfer of R64.

PMID- 9281492
TI  - Molecular analysis of a mobilizable theta-mode trimethoprim resistance plasmid
      from coagulase-negative staphylococci.
AB  - The Staphylococcus epidermidis plasmid pSK639 is the prototype of a newly
      described family of small plasmids identified in clinical staphylococcal
      isolates. pSK639 is 8 kb in length and possesses a composite structure consisting
      of an IS257-flanked segment mediating trimethoprim resistance (Tpr), and regions
      responsible for replication and mobilization of the plasmid. Comparative sequence
      analysis suggests that a pSK639-like plasmid may represent a progenitor of
      previously identified staphylococcal Tpr determinants related to the transposon
      like structure, Tn4003. In contrast to the small staphylococcal plasmids
      characterized to date that all utilize a rolling circle mode of replication, the
      replication region of pSK639 was found to contain features typical of an iteron
      controlled theta-mode replicon. pSK639 is the first small plasmid of this type to
      be identified in the staphylococci.

PMID- 9281493
TI  - A novel retron that produces RNA-less msDNA in Escherichia coli using reverse
      transcriptase.
AB  - Bacterial retroelements, or retrons, use reverse transcriptase (RT) to produce a
      multicopy single-stranded DNA (msDNA) molecule that is covalently linked to RNA.
      In these studies we show that a retron from Escherichia coli 110, a clinical
      isolate, produces a novel RNA-less msDNA with a 5' phosphate residue. The msDNA
      is a 74-nucleotide single-stranded DNA molecule with a stable stem-loop structure
      without a mismatched base pair. Only the genes encoding msDNA (msd), msdRNA
      (msr), and RT (ret) are required to produce the msDNA molecule. The organization
      of these genes on the retron was similar to that of other elements producing
      branched msDNA-RNA. The conserved guanine, which is the branched residue in msDNA
      RNA complexes and is essential for branch formation, is also present. Site
      directed mutagenesis showed that this guanine is essential for the production of
      RNA-less msDNA. We postulate that the RNA-less msDNA in strain 110 is produced by
      nucleolytic cleavage of the branched msDNA-RNA compound.

PMID- 9281494
TI  - Improved broad-host-range RK2 vectors useful for high and low regulated gene
      expression levels in gram-negative bacteria.
AB  - This report describes the construction and use of improved broad-host-range
      expression vectors based on the previously constructed pJB137 and pJB653 plasmids
      (Blatny et al., 1997). These vectors contain the minimal replicon of RK2 and the
      inducible Pu or Pm promoters together with their regulatory xylR or xylS genes,
      respectively, from the Pseudomonas putida TOL plasmid pWWO. A set of ATG vectors
      were derived from pJB653, and these vectors are characterized by the relatively
      small size, the presence of multiple cloning sites downstream of Pm, the
      establishment of their nucleotide sequence, the presence of RK2 oriT, and
      different antibiotic selection markers. The copy numbers of all the vectors can
      easily be modified by using copy-up mutations of the trfA gene, required for
      initiation of replication of RK2 replicons. The vectors were used to study the
      expression levels of the Acetobacter xylinum phosphoglucomutase gene celB and the
      two commonly used reporter genes luc and cat in Escherichia coli, Pseudomonas
      aeruginosa, and Xanthomonas campestris. Good induction properties and tight
      regulation of Pm were achieved in all three species tested, and higher gene
      expression levels were obtained by using the ATG vectors compared to pJB653. By
      introducing different trfA copy-up mutations into the vectors, a wide range of
      gene expression levels from Pu and Pm were obtained in E. coli. Induced
      expression levels of luc, cat, and celB from Pm were found to be comparable to or
      higher than those from the Ptrc and PT7 promoters located on high copy number
      plasmids. The induced levels of Luc activity were higher in P. aeruginosa than in
      E. coli, indicating that these vectors may be useful for maximization of gene
      expression in strains other than E. coli. We believe that the well-characterized
      vectors described here are useful for gene expression studies and routine cloning
      experiments in many Gram-negative bacteria.

PMID- 9281495
TI  - Complete nucleotide sequence of the replicator region of Paracoccus
      (Thiobacillus) versutus pTAV1 plasmid and its correlation to several plasmids of
      Agrobacterium and Rhizobium species.
AB  - The complete nucleotide sequence of the replicator region of pTAV1, a cryptic,
      low copy number plasmid of Paracoccus versutus, was determined. The minimal
      replicon sequence (3149 bp) included in pTAV203/18 contains two open reading
      frames with coding capabilities for putative polypeptides of 23.8 (RepX) and 46
      kDa (RepC'). The two genes have the same transcriptional polarity and both seem
      to be essential for replication of pTAV203. The predicted amino acid sequence of
      RepC' shows significant homology with the major replication-associated proteins
      of several Agrobacterium and Rhizobium plasmids. A probable origin of replication
      (oriV) was proposed to be localized at the 3' terminal end of the repC' gene.

PMID- 9281496
TI  - Cryptic plasmid pKA22 isolated from the naphthalene degrading derivative of
      Rhodococcus rhodochrous NCIMB13064.
AB  - Cryptic plasmids were found in Rhodococcus rhodochrous NCIMB13064 derivatives
      which had lost the ability to utilize short-chain 1-chloroalkanes (chain length
      C3-C10) and had acquired the ability to degrade naphthalene. The reversions of
      these derivatives to the original phenotype were accompanied by the loss of the
      cryptic plasmids. The 4969-bp pKA22 plasmid was cloned in Escherichia coli and
      sequenced. This plasmid encodes a putative 33,200-Da protein which contains
      motifs typical of theta replicase proteins and shows a high degree of similarity
      to a putative theta replicase from Brevibacterium linens plasmid pRBL1 and to a
      putative protein encoded by ORF1 of the plasmid pAL5000 from Mycobacterium
      fortuitum. Two sets of long direct repeats were found in pKA22 which may be
      involved in the replication of the plasmid and recombination processes.

PMID- 9281497
TI  - Unwelcomed guests with master keys: how HIV uses chemokine receptors for cellular
      entry.

PMID- 9281498
TI  - Structure of Broadhaven virus by cryoelectron microscopy: correlation of
      structural and antigenic properties of Broadhaven virus and bluetongue virus
      outer capsid proteins.
AB  - The three-dimensional structure of Broadhaven virus (BRDV) has been determined to
      23 A resolution by cryoelectron microscopy and image processing. As predicted
      from sequence homology, the BRDV structure resembles that of bluetongue virus
      (BTV) with the notable exception of one of the outer shell proteins. The cores of
      BRDV and BTV are identical at medium resolution; they have a diameter of 710 A
      and the VP7 trimers are arranged on a T = 13 icosahedral lattice. The outer shell
      proteins, VP5 of BRDV and BTV, have roughly the same molecular weight while VP4
      of BRDV is only half the molecular weight of the corresponding VP2 of BTV. This
      size difference allows unambiguous determination of the identity of the
      triskelion shape as trimers of VP4 of BRDV (VP2 of BTV). The VP4 of BRDV sits on
      the VP7 trimers and projects outwards 40 A, giving the capsid an overall diameter
      of 790 A. This contrasts with VP2 of BTV, which projects outwards 95 A to give
      the capsid a diameter of 900 A. The difference in accessibility of the outer
      shell proteins of BRDV and BTV correlates with the difference in antigenic
      properties of these viral proteins. The shape of the BRDV VP5 indicates that it
      too is a trimer, thus implying that there are 360 copies of VP5 and 180 copies of
      VP4 per virion.

PMID- 9281499
TI  - How lysophosphatidylcholine inhibits cell-cell fusion mediated by the envelope
      glycoprotein of human immunodeficiency virus.
AB  - We have investigated the effect of lysophosphatidylcholine (LPC) on fusion of
      cells expressing the envelope glycoprotein of HIV-1, gp120/gp41, with cells
      expressing the receptor for this virus, CD4. Fusion was inhibited by micromolar
      concentrations of LPC added from an aqueous stock solution, but not by membrane
      associated LPC or LPC produced in the membrane by the action of phospholipase A2.
      No inhibition was found for LPCs with acyl chain lengths shorter than 12 carbon
      atoms, and the inhibitory effect of longer molecules increased with their length.
      gp120-CD4 specific cell-cell binding was inhibited with a chain length dependence
      corresponding to that of fusion, but with palmitoyl-LPC, fusion was more strongly
      affected than binding. These data indicate that gp120/gp41-induced fusion is
      inhibited by LPC because LPC affects viral protein-host cell binding and not
      because LPC prevented the formation of lipid intermediates required for fusion.

PMID- 9281500
TI  - The three subunits of the polymerase and the nucleoprotein of influenza B virus
      are the minimum set of viral proteins required for expression of a model RNA
      template.
AB  - The genes encoding the nucleoprotein, PB1, PB2, and PA proteins of the influenza
      virus strain B/Panama/45/90 have been cloned under control of the T7 RNA
      polymerase promoter of plasmid pGEM-3. Transfection of the recombinant plasmids
      obtained into mammalian cells, which had been infected with a vaccinia virus
      encoding the T7 RNA polymerase, resulted in expression of the expected influenza
      B virus polypeptides. Moreover, it is shown that coexpression of the four
      recombinant core proteins in COS-1 cells reconstituted a functional polymerase
      capable of expressing a synthetic influenza B virus-like CAT RNA. By using the
      influenza B virus recombinant plasmids and a set of pGEM-derived plasmids
      encoding the homologous core proteins of the influenza A virus A/Victoria/3/75
      (I. Mena et al. (1994). J. Gen. Virol. 75, 2109-2114), the capabilities of homo-
      and heterotypic mixtures of the four core proteins to express synthetic type A
      and B CAT RNAs were analyzed. Both the influenza A and B virus polymerases were
      active in expressing, albeit with reduced efficiencies, the heterotypic model CAT
      RNAs. However, none of all possible heterotypic mixtures of the core proteins
      reconstituted a functional polymerase. In order to fully characterize the
      recombinant plasmids obtained, the nucleotide sequences of the cloned genes were
      determined and compared to sequences of other type B virus isolates. The results
      obtained from these latter analyses are discussed in terms of the conservation
      and evolution of the influenza B virus core genes.

PMID- 9281501
TI  - In vitro reconstitution of an intermediate assembly stage of vaccinia virus.
AB  - A novel method is described which facilitates the in vitro assembly of one step
      in the life cycle of vaccinia virus, the formation of the spherical immature
      virus (IV). For this, advantage was taken of the ability of rifampicin to
      reversibly block the assembly of the IV. Rifampicin-treated, vaccinia virus
      infected HeLa cells were permeabilized with streptolysin O (SLO) and the
      endogenous cytosol was allowed to exit the cells at 4 degrees . Subsequently,
      exogenous cytosol from infected or uninfected HeLa cells as well as an ATP
      regenerating system were added and the cells were incubated for different times
      at 37 degrees in the absence of rifampicin. The preparations were then evaluated
      by thin section EM. Our data show that in the presence of infected or uninfected
      cell cytosol and ATP a significant fraction of cells could reconstitute IV
      assembly in vitro. Under no conditions were we able to reconstitute any later
      stages of assembly. The potential of this system for the in vitro reconstitution
      of viral assembly in general is discussed.

PMID- 9281502
TI  - A cottontail rabbit papillomavirus strain (CRPVb) with strikingly divergent E6
      and E7 oncoproteins: An insight in the evolution of papillomaviruses.
AB  - We previously observed that warts induced by an isolate of cottontail rabbit
      papillomavirus (CRPV) showed incomplete instead of systemic regression in some
      domestic rabbits. We report that the viral isolate contained, as a major
      component, a CRPV strain (CRPVb) showing an unexpectedly high divergence in the
      E6 and E7 open reading frames (ORFs), compared to the prototype CRPVa present in
      the isolate as a minor component. The E6 and E7 oncoproteins of CRPVa and -b
      disclosed only 87.5% identical amino acids and differed in size by three and two
      amino acids, respectively. This divergence involved (i) a great number (4.4%) of
      nucleotide substitutions and a high rate (83.3%) of nonsynonymous mutations; (ii)
      mutations changing the E6 and E7 stop codons; and (iii) in-frame sequence
      insertions in the E6 ORF (18 nucleotides) and downstream of the mutated E7 stop
      codon (6 nucleotides), both likely to result from a duplication of adjacent
      sequences. These extensive differences could account for distinct biological and
      antigenic properties. Strikingly, only four (0.8%) amino acids of the L1 major
      capsid protein were variable. Thus, it seems likely that sequence duplications
      and mutations affecting stop codons exert a strong selection pressure on the
      fixation of nonsynonymous mutations and that phylogenetic calculations based only
      on point mutations may misevaluate the time scale of the evolution of
      papillomaviruses.

PMID- 9281503
TI  - Methyltransferase activity of the insect orbivirus JKT-7400: photoaffinity
      labeling of a minor virion protein, VP4, with S-adenosylmethionine.
AB  - JKT-7400 virus is an orbivirus originally isolated from Culex mosquitoes. In
      earlier work we had described the viral structural proteins and presented
      evidence suggesting that a minor protein, VP6, located in the viral core was the
      viral guanylyltransferase. We now show that gradient-purified JKT-7400 virions
      possess a methyltransferase (MTase) activity which can use GTP or GDP as the
      methyl acceptor. The apparent Km of the MTase for S-adenosylmethionine (AdoMet)
      was 25 microM. Photoaffinity labeling experiments in which 3H-[methyl]-AdoMet was
      incubated with virions or viral cores demonstrated labeling of VP4, a minor
      protein present in the viral core, suggesting that this protein is the viral
      MTase. Labeling of VP4 was inhibited by addition of unlabeled AdoMet or S
      adenosylhomocysteine (AdoHcy).

PMID- 9281504
TI  - The immunoreceptor tyrosine-based activation motif of Epstein-Barr virus LMP2A is
      essential for blocking BCR-mediated signal transduction.
AB  - The Epstein-Barr virus (EBV) latent membrane protein 2A (LMP2A) blocks B-cell
      receptor (BCR) signal transduction in EBV-immortalized B lymphocytes in vitro.
      The cytoplasmic amino-terminal domain of LMP2A contains an immunoreceptor
      tyrosine activation motif (ITAM). ITAMs consist of paired tyrosine and leucine
      residues and play a central role in signal transduction of the BCR and the T-cell
      receptor (TCR). To investigate the importance of the LMP2A ITAM, two EBV
      recombinants were constructed, each containing a tyrosine-to-phenylalanine point
      mutation at amino acid 74 or 85 within the ITAM of LMP2A. Tyrosine
      phosphorylation, calcium mobilization, and induction of BZLF1 expression were no
      longer blocked in the LMP2A ITAM mutant LCLs following BCR cross-linking. In
      addition, the Syk protein tyrosine kinase (PTK) was unable to bind LMP2A in
      unstimulated LCLs infected with either of the LMP2A ITAM mutants. Analysis of Syk
      phosphorylation before and after BCR cross-linking in the LMP2A mutant ITAM LCLs
      compared with wild-type EBV LCLs indicates a specific role of the LMP2A ITAM on
      the LMP2A-mediated negative effect on the Syk PTK. These data indicate the
      importance of the LMP2A ITAM motif in the LMP2A-mediated block on BCR signal
      transduction and position the role of the Syk PTK as being central to the
      function of LMP2A.

PMID- 9281506
TI  - The Sendai virus C protein binds the L polymerase protein to inhibit viral RNA
      synthesis.
AB  - The Sendai virus nested set of C proteins which are expressed in an alternative
      open reading frame from the P mRNA has been shown to downregulate viral RNA
      synthesis. Utilizing a glutathione S-transferase (gst) C fusion protein (gstC),
      we have shown that C protein forms a complex with the L, but not the P, subunit
      of the viral RNA polymerase. When P, L, and gstC are coexpressed, an oligomer of
      P, through its interaction with L, is also bound to beads. Since binding of C to
      L in the P-L complex does not disrupt P binding, the C and P binding sites appear
      to be different. GstC binding to L occurs only when the proteins are coexpressed
      in the same cell. The gstC, but not gst, protein inhibits viral transcription in
      vitro, showing that the fusion protein retains biological function. Pulse-chase
      experiments of the various complexes show that L protein synthesized alone has a
      half-life of 1. 2 hr, which is increased 12.5-fold by binding P, but is not
      significantly increased by binding gstC. Analyses of complex formation with
      truncations of L protein show that the C-terminal 1333 amino acids of L are not
      required for binding C. The dose-response curves show that replication of the
      genomic DI-H RNA is more sensitive to inhibition by C protein than is the
      synthesis of DI leader RNA, suggesting that the downregulation of RNA synthesis
      may be more complex than just the inhibition of the initiation of RNA synthesis.

PMID- 9281505
TI  - Baculovirus expression of a human G2-specific, neutralizing IgG monoclonal
      antibody to Puumala virus.
AB  - We amplified by polymerase chain reaction the heavy- and light-chain antibody
      genes of a human hybridoma secreting a neutralizing, IgG monoclonal antibody to
      the G2 protein of Puumala virus. The heavy- and light-chain genes were cloned and
      sequenced and the deduced amino acids were aligned with those of other human
      antibodies to identify the constant and variable regions. The genes were cloned
      into the baculovirus plasmid transfer vector pACUW51 such that the heavy-chain
      and light-chain genes were under control of the baculovirus polyhedrin or p10
      promoters, respectively. The transfer vector plasmid was cotransfected into
      cultured Spodoptera frugiperda (Sf9) cells with linearized DNA of the baculovirus
      Autographa californica nuclear polyhedrosis virus, and recombinant baculoviruses
      were selected by plaque formation on monolayers of Sf9 cells. Expression and
      secretion of an IgG monoclonal antibody was confirmed by assay of recombinant
      infected Sf9 cell supernatants for the presence of the heavy and light chains.
      Specificity of the expressed human antibody was determined by immune
      precipitation of radiolabeled Puumala virus proteins and by ELISA with Puumala
      virus-infected cell lysates. Similar quantities of the expressed IgG and the
      authentic monoclonal antibody neutralized Puumala virus in plaque-reduction
      neutralization assays. Neither the authentic nor the recombinant antibody could
      passively protect hamsters from challenge with Puumala virus; however, our
      results demonstrate the potential of this methodology for production of
      biologically active neutralizing antibodies.

PMID- 9281507
TI  - Isolation of sooty mangabey simian T-cell leukemia virus type I [STLV-I(sm)] and
      characterization of a mangabey T-cell line coinfected with STLV-I(sm) and simian
      immunodeficiency virus SIVsmmPBj14.
AB  - It has been postulated that dual infections of humans with human immunodeficiency
      virus (HIV) and human T-cell leukemia/lymphotropic virus (HTLV) may potentiate
      disease progression. Counterparts of both of these pathogenic human retroviruses
      have been identified in various simian species indigenous to Asia and Africa,
      including sooty mangabey monkeys (Cercocebus atys). Using peripheral blood
      mononuclear cells (PBMC) from a mangabey naturally infected with both SIV and
      STLV-I, T-cell lines were established and maintained continuously for more than 3
      years; these cell lines harbored only a newly identified mangabey STLV-I(sm) or
      both STLV-I(sm) and the acutely lethal variant SIVsmmPBj14. The dually infected
      cell line (FEd-P14) was established by de novo infection of mangabey PBMC with
      SIVsmmPBj14. This cell line was characterized by multiple assays which showed
      that structural proteins encoded by both viruses were produced in large
      quantities, but that the predominant viral glycoprotein on the cell surface was
      the STLV-I(sm) Env. Unusual interactions of the two retroviral glycoproteins were
      suggested by the formation of syncytia between Raji and the FEd-P14 cells, but
      not between Raji and simian cells infected with only one retrovirus or human
      cells infected with HTLV-I. The STLV-I(sm) strain obtained from the sooty
      mangabey was transmitted to normal macaque and mangabey PBMC and was shown to be
      unique by sequencing of the entire env gene. STLV-I(sm) from this African species
      was more closely related to "cosmopolitan" HTLV-I strains than to the prototypic
      STLV-I from an Asian pig-tailed macaque. In vitro and in vivo studies of STLV
      I(sm) and SIVsmm, both isolated from a naturally infected mangabey monkey, may
      provide insight into disease induction and manifestations associated with
      coinfection by their human counterparts.

PMID- 9281509
TI  - Persistent echovirus infection of mouse cells expressing the viral receptor VLA
      2.
AB  - Mouse cells are not susceptible to infection with echovirus 1 (EV-1) because they
      lack the viral receptor, human VLA-2. Two mouse fibroblast cell lines, L cells
      and 3T3 cells, were made susceptible to EV-1 infection after transformation with
      cDNAs of human VLA-2. After EV-1 infection, L cell transformants of human VLA-2
      (alpha2beta1 L cells) develop cytopathic effect (CPE) as expected, while 3T3 cell
      transformants of human VLA-2 (alpha2beta1 3T3 cells) or the alpha2 subunit of
      human VLA-2 (alpha2 3T3 cells) become persistently infected. The distinct outcome
      is not a result of differential virus growth on these transformants because one
      step growth curve analysis reveals little difference in EV-1 replication in both
      cell lines. In addition, 3T3 cell transformants expressing the poliovirus
      receptor (Pvr 3T3 cells) are lysed during poliovirus infection, suggesting that
      3T3 cells are not intrinsically resistant to CPE caused by enterovirus infection.
      The results of limit dilution assays indicate that all EV-1-infected alpha2 3T3
      cells produce infectious virus. All EV-1-infected alpha2 3T3 cells remain viable
      after EV-1 infection, and the kinetics of cell growth were not altered. FACS
      analysis reveals that receptor down-regulation is not involved in the
      establishment of persistent infection. Furthermore, inhibition of host protein
      synthesis was not observed in EV-1-infected alpha2 3T3 or alpha2beta1 L cells.
      Since alpha2beta1 L cells are lysed by EV-1 infection, these findings suggest
      that virus-induced translation inhibition is not a determinant of cell killing.

PMID- 9281508
TI  - Characterization of an overlapping CD8+ and CD4+ T-cell epitope on rubella capsid
      protein.
AB  - A synthetic peptide corresponding to rubella virus capsid protein residues 263 to
      275 which contains an epitope recognized by a cloned CD4+ cytotoxic T-lymphocyte
      (CTL) line was used to induce CD8+ T-cell lines specific to this peptide. A
      peptide-specific CD8+ CTL clone was derived and characterized. This peptide
      specific CD8+ CTL clone exhibited cytotoxicity against target cells infected by a
      vaccinia recombinant virus expressing rubella virus capsid protein, but not by
      target cells infected by vaccinia recombinant virus expressing rubella virus E1
      or E2 envelope proteins. Analysis of HLA class I restriction of the CD8+ CTL
      clone revealed that A11 and A3 were restrictive elements. Fine mapping with
      truncated and overlapping peptide analogs revealed a nonamer sequence, C(264
      272), as the T-cell epitope eliciting stronger cytotoxicity. Two anchor residues
      for binding to HLA A11 and A3 were identified at position 2 (isoleucine) and at
      position 9 (histidine) or at position 8 (arginine) of the epitope sequence. The
      identification of overlapping CD4+ and CD8+ T-cell epitopes within the capsid
      protein sequence C(263-275) implicates a strategy for using such epitopes in a
      candidate peptide-based rubella vaccine.

PMID- 9281510
TI  - Histones as a target for influenza virus matrix protein M1.
AB  - Matrix protein M1 purified from influenza A and B viruses has been analyzed for
      its ability to specifically interact with cellular proteins by immune
      coprecipitation and by an in vitro binding assay on nitrocellulose on PVDF
      membranes. When M1 was mixed with lysates of uninfected cells there was selective
      binding of histones H2A, H2B, H3, and H4. Week binding of H1 was also observed.
      The binding specificity of M1 was confirmed by using purified histones. The M1
      histone complexes were dependent on pH and ionic strength, indicating
      electrostatic interactions. Chemical cleavage of M1 by formic acid into an N
      terminal 9-kDa fragment and a C-terminal 18-kDa fragment did not abolish
      interaction with histones. However, after treatment with 1 M sodium chloride
      cleaved M1 no longer bound to histones, whereas uncleaved M1 showed an increased
      binding activity after salt treatment. These findings suggest that both N- and C
      terminal domains of M1 are involved in histone binding and that conformation of M
      is an important factor in this interaction. The data support the notion that
      there is specific interaction of M1 with nucleosomes during the nuclear phase of
      influenza virus replication.

PMID- 9281511
TI  - In situ localization of the putative movement protein (pr17) from potato leafroll
      luteovirus (PLRV) in infected and transgenic potato plants.
AB  - The potato leafroll virus (PLRV) 17-kDa protein (pr17), the putative movement
      protein for this phloem-limited luteovirus, was localized on ultrathin sections
      of leaves from PLRV-infected and transgenic potato plants. The transgenic plants
      expressed the entire viral genome from a full-length cDNA copy (PLRVfl) or only
      the gene encoding pr17 (ORF4) under the control of the cauliflower mosaic virus
      35S promoter. Virus-infected and PLRVfl-transgenic plants developed symptoms
      typical of virus infection, whereas pr17-transgenic plants did not display
      symptoms or ultrastructural alterations. Immunogold electron microscopy using an
      anti-pr17-serum detected pr17 in plasmodesmata, in virus-induced vesicles, in
      mitochondria, and in chloroplasts of phloem cells, in PLRV-infected as well as
      PLRVfl-transgenic plants. In addition, in transgenic plants, pr17 was expressed
      in mesophyll cells (which are not infected by PLRV under natural conditions) and
      localized to the same sites as in phloem cells, except in plasmodesmata. In
      contrast, in pr17-transgenic plants the protein was never observed on organelles,
      but was almost exclusively associated with plasmodesmata of all leaf cell types,
      indicating that the targeting of pr17 to plasmodesmata is an intrinsic property
      of the protein. These results support the role of pr17 in PLRV movement.

PMID- 9281512
TI  - Recovery of infectious human parainfluenza virus type 3 from cDNA.
AB  - Infectious HPIV3 was produced by the intracellular coexpression of four plasmid
      borne cDNAs. These separately encoded a complete HPIV3 genome (negative-sense),
      the HPIV3 nucleocapsid protein N, the phosphoprotein P, and the polymerase
      protein L. The cDNA-encoded HPIV3 genome differed from the JS wildtype (wt)
      strain of HPIV3 used in its construction by seven point mutations: four of these
      are silent mutations in the HN or L gene coding regions that serve as markers of
      a cDNA-derived virus, two were introduced to create an amino acid substitution
      that ablates an epitope recognized by the HN-specific monoclonal neutralizing
      antibody 423/6, and the remaining point mutation results in an incidental amino
      acid substitution in the HN protein at amino acid position 263. The four plasmids
      were transfected into HEp-2 cell monolayers and their expression was driven by T7
      RNA polymerase supplied by a vaccinia virus recombinant. The titer of virus
      present in the harvested transfection supernatant was low (<5 PFU/ml), and the
      recovered recombinant virus (rJS) retained each of the seven mutations present in
      the cDNA from which it was derived. Despite the introduced and incidental
      mutations, rJS retained the wt phenotypes as regards replication at elevated
      temperature in vitro and efficient replication in the upper and lower respiratory
      tract of hamsters. rJS was also recovered from a cDNA encoding a complete
      antigenome (positive-sense) with slightly greater efficiency than from the
      negative-sense construct. The ability to generate infectious HPIV3 from cDNA
      should greatly enhance our ability to develop new live-attenuated parainfluenza
      virus vaccines, including chimeric PIV1 and PIV2 vaccines, and to understand the
      genetic basis of attenuation of PIV3 candidate vaccines.

PMID- 9281513
TI  - Comparison of the role of 5' terminal sequences of alfalfa mosaic virus RNAs 1,
      2, and 3 in viral RNA replication.
AB  - The 5' untranslated regions (UTRs) of the genomic RNAs 1, 2, and 3 of alfalfa
      mosaic virus (AMV) are 100, 54, and 345 nucleotides (nt) long, respectively, and
      lack extensive sequence similarity to each other. RNA 3 encodes the movement
      protein P3 and the coat protein and can be replicated in transgenic tobacco
      plants expressing the replicase proteins P1 and P2 (P12 plants). 5' Cis-acting
      sequences involved in RNA 3 replication have been shown to be confined to the 5'
      UTR. When the 5' UTR of RNA 3 was replaced by the 5' UTRs of RNAs 1 or 2, the
      recombinant RNA was not infectious to P12 plants. Also, when the P3 gene in RNA 3
      was put under the control of a subgenomic promoter and the 5' UTR of this RNA was
      replaced by 5' terminal RNA 1 sequences of 103 to 860 nt long or RNA 2 sequences
      of 57 to 612 nt long, no accumulation of the hybrid RNAs was observed. Deletion
      of the 5' 22 nucleotides of RNA 3 resulted in the accumulation of a major progeny
      that lacked the 5' 79 nt. However, when the 5' 22 nucleotides of RNA 3 were
      replaced by the complete 5' UTR of RNA 1 or 5' sequences of RNAs 1, 2, or 3 with
      a length of 5 to 15 nt, accumulation of the full-length mutant RNAs was observed.
      The effect of mutations in the 5' viral sequences of 5 to 15 nt was analyzed. It
      is concluded that although elements within nucleotides 80-345 of the 5' UTR of
      RNA 3 are sufficient for replication, a specific sequence of 3 to 5 nt is
      required to target the replicase to an initiation site corresponding to the 5'
      end of the RNA.

PMID- 9281515
TI  - Intracisternal A-type particles express their proteinase in a separate reading
      frame by translational frameshifting, similar to D-type retroviruses.
AB  - Intracisternal A-type particles (IAP) are defective endogenous retroviruses that
      accumulate in the endoplasmic reticulum of rodent cells. IAP genomes share
      extensive sequence homologies with D-type retroviruses, but were presumed to
      express the viral proteinase (PR) as part of the gag open reading frame (ORF)
      while D-type retroviruses express PR in a separate ORF. Here we show that
      expression of the murine IAP element MIA14 yields three major translation
      products, corresponding to the Gag, Gag-PR, and Gag-PR-Pol polyproteins. Sequence
      analysis revealed that MIA14 PR is encoded in its own reading frame, separate
      from gag and pol. Frameshifting occurred with an efficiency of approximately 25%
      between the gag and pro ORFs and 35% between pro and pol. The region containing
      the putative gag-pro frameshift signal consists of a heptanucleotide slippery
      sequence (A6C) and a stem-loop structure probably forming a pseudoknot. Deletion
      of this structure element almost completely abolished frameshifting. Insertion of
      an additional base next to the frameshift signal placed gag and pro in the same
      ORF and resulted in predominant formation of Gag-PR and Gag-PR-Pol polyproteins
      which were not processed following in vitro translation. Expression of a similar
      construct in tissue culture cells, on the other hand, led to efficient
      intracellular processing of the mutant polyproteins.

PMID- 9281514
TI  - Membrane permeability changes induced in Escherichia coli by the SH protein of
      human respiratory syncytial virus.
AB  - The small hydrophobic (SH) protein of human respiratory syncytial virus (HRSV)
      has been efficiently expressed in Escherichia coli. In analogy to small
      hydrophobic proteins encoded by other RNA viruses, membrane permeability changes
      to low-molecular-weight compounds were detected in bacteria expressing HRSV SH
      protein. These changes implied, at least, the entry of both the protein synthesis
      inhibitor hygromycin B and the beta-galactoside substrate o-nitrophenyl-beta-d
      galactopyranoside and the exit of preloaded [3H]uridine from bacterial cells.
      Site-directed mutagenesis indicated that the C-terminal end of SH is needed for
      induction of membrane permeability changes. In addition, amino acid substitution
      at residue 32 (Ile to Lys) abolished that activity. This was correlated with a
      drastic increase in SH electrophoretic mobility and a decrease of the predicted
      values of alpha-helix for all residues of the SH transmembrane domain. Other
      sequence changes have either partial effect or no effect on the membrane
      permeability changes induced by the SH protein. However, none of the mutations
      abrogated the association of SH protein with bacterial membranes, indicating that
      incorporation of SH protein to membranes is not sufficient to induce the observed
      changes. Membrane permeability changes then might provide a useful test for the
      identification of key amino acid residues in this unique HRSV gene product.

PMID- 9281516
TI  - Phosphorylation of the Sendai virus M protein is not essential for virus
      replication either in vitro or in vivo.
AB  - A large proportion of intracellular Sendai virus (SeV) M proteins is
      phosphorylated, but in mature virions the M protein is not phosphorylated or
      dephosphorylated. Phosphorylated M protein in cells is bound to the cytoskeletal
      components more firmly than unphosphorylated M protein. Thus it has been
      hypothesized that M protein phosphorylation plays an important role in the virus
      life cycle, especially in the step of maturation. Here, a transient expression
      mutation experiment of the M gene demonstrated that a change of the Ser residue
      at the 70th position from the N-terminus to Ala (S70A) totally abolished M
      protein phosphorylation, strongly suggesting that this residue is phosphorylated.
      The mutated M gene was then placed in the corresponding region in the cDNA
      plasmid which generates a full-length antigenome SeV RNA, and a mutant SeV M-S70A
      was successfully recovered from the cDNA. This mutant virus was indeed defective
      in M protein phosphorylation but did not differ at all from the wild-type SeV
      recovered from the parental cDNA either in the replication kinetics and plaque
      morphology in cultured cells or in in vivo replication and pathogenicity for
      mice. We thus concluded that no phosphorylation of the M protein was required for
      SeV replication either in vitro or in vivo.

PMID- 9281517
TI  - Field and vaccine strains of fowlpox virus carry integrated sequences from the
      avian retrovirus, reticuloendotheliosis virus.
AB  - For baculoviruses and herpesviruses, integration of transposons or retroviruses
      into the virus genome has been documented. We report here that field and vaccine
      strains of fowlpox virus (FPV) carry integrated sequences from the avian
      retrovirus, reticuloendotheliosis virus (REV). Using PCR and hybridization
      analysis we observed that vaccine and field strains of FPV carry REV sequences
      integrated into a previously uncharacterized region of the right 1/3 of the FPV
      genome. Long-range PCR, hybridization, and nucleotide sequence determination
      demonstrated that one vaccine strain (FPV S) and recently isolated field strains
      carry a near-full-length REV provirus. For another vaccine strain (FPV M) a
      rearranged remnant of the LTR was found at the same insertion site. By Western
      blotting and reverse transcriptase assays we were unable to demonstrate free REV
      in supernatants of FPV S cultures. The near-full-length REV provirus integrated
      into the FPV genome is infectious since FPV S DNA gave rise to REV upon
      transfection into chicken embryo fibroblasts. Upon infection of chickens with FPV
      S, all chickens developed high-titered antibodies to REV, and REV was isolated
      from the blood of half of the inoculated chickens. Our observations add to the
      list of targets for retrovirus integration into DNA virus genomes. The
      integration of a near-full-length, and apparently infectious, REV provirus into
      FPV provides additional transmission routes for the retrovirus by way of the
      infectious cycle of FPV, including the possibility of mechanical transmission by
      biting insects since FPV is believed to be transmitted by this route. For large
      DNA viruses, including the poxviruses, retrovirus integration with attendant
      possibilities of gene transduction may be an important mechanism for virus
      evolution, including the acquisition of cellular genes with the potential to
      modify virus virulence and pathogenicity.

PMID- 9281519
TI  - Use of synthetic peptides to identify measles nucleoprotein T-cell epitopes in
      vaccinated and naturally infected humans.
AB  - Recombinant measles nucleoprotein (N) and synthetic peptides spanning the length
      of the N-protein-coding region were used with a proliferation assay to identify
      human T-cell epitopes in vaccinated and naturally infected adults. A number of
      epitopes were mapped to specific regions of the measles virus N. The
      proliferative response of at least two donors was mediated by CD4(+) T cells in
      association with HLA DR antigens. Over 70% of all donors tested responded to
      peptides representing amino acids 271-290, 367-386, 400-420, and 483-502,
      suggesting that these peptides may be broadly recognized within an HLA diverse
      population. The most frequently recognized T-cell epitopes in both naturally
      infected and vaccinated donors were located in the genetically heterogeneous
      carboxy-terminal half of the N. Analysis of patterns of peptide reactivity among
      vaccinated and naturally infected subjects identified several regions of
      potential difference between these two groups. Peptides 221-240 and 237-256 were
      recognized among 100% of naturally infected donors but among only 37.5% of
      vaccinated donors and therefore may be of further interest in studies to
      investigate induction of lifelong versus transient immunity to measles. Use of
      chimeric molecules containing multiple well-characterized T- and B-cell epitopes
      or genetic alteration of attenuated vaccine virus to enhance critical T-cell
      responses may eventually lead to the development of a vaccine candidate that can
      more closely model the patterns of immune response elicited by wild-type virus.

PMID- 9281518
TI  - A conserved African swine fever virus IkappaB homolog, 5EL, is nonessential for
      growth in vitro and virulence in domestic swine.
AB  - An African swine fever virus (ASFV) gene with similarity to the cellular
      inhibitor of NFkappaB (IkappaB) was described in the pathogenic African isolate
      Malawi Lil-20/1 (ORF 5EL) and a cell-culture-adapted European virus, BA71V (ORF
      A238L). Recently, this gene was shown to be a functional IkappaB homolog capable
      of downregulating NFkappaB-regulated gene expression. This observation suggests
      the gene may be of significance to aspects of ASFV pathogenesis and virulence in
      domestic swine by interfering with a normal antiviral host response. Here we
      show, using nucleotide sequence analysis, that 5EL is highly conserved among
      various African and European pathogenic field isolates and that in all cases its
      similarity to IkappaB genes is limited to the presence of four low complexity
      ankyrin repeats in the ASFV gene. The 5EL gene of Malawi Lil-20/1 encodes a 28
      kDa protein which was expressed early in virus-infected macrophage cell cultures
      with maximum levels observed at 3 to 5 hr postinfection. To study gene function,
      a Malawi Lil-20/1 5EL gene deletion mutant (Delta5EL) was constructed. Growth
      characteristics of Delta5EL in porcine macrophage cell cultures were
      indistinguishable from those of the parental virus. And, Delta5EL exhibited an
      unaltered parental Malawi Lil-20/1 disease and virulence phenotype in domestic
      swine. Thus, although highly conserved among ASFV isolates, 5EL is nonessential
      for growth in porcine macrophages in vitro and for viral virulence in domestic
      swine. A possible role for this gene in transmission of ASFV in nature, a setting
      which involves the cycling of ASFV between two highly adapted hosts, Ornithodoros
      ticks and warthogs or bush pigs, in sub-Saharan Africa is discussed.

PMID- 9281521
TI  - The UL13 protein kinase and the infected cell type are determinants of
      posttranslational modification of ICP0.
AB  - The herpes simplex virus infected-cell protein 0 (ICP0) acts as a promiscuous
      transactivator of genes introduced into eukaryotic cells by transfection or
      infection. The protein is highly posttranslationally modified by phosphorylation
      and nucleotidylylation. We have examined the electrophoretic mobility and
      phosphorylation of ICP0 in Vero and rabbit skin cells infected with wild-type
      virus or viruses from which the UL13 gene (DeltaUL13) encoding a protein kinase
      or the alpha22/US1.5 genes (Deltaalpha22/DeltaUS1.5) encoding putative
      transcriptional factors has been deleted. We report the following: (i) The
      accumulation of ICP0 and the electrophoretic mobility of ICP0 were dependent on
      the nature of the infected cell type and the presence of UL13. ICP0 encoded by
      wild-type virus accumulated to maximum levels earlier in infected Vero cells and
      its electrophoretic mobility was slower than that made in rabbit skin cells. In
      both Vero and rabbit skin cells infected with the DeltaUL13 virus, the prevailing
      ICP0 form migrated faster than that accumulating in the corresponding cells
      infected with wild-type virus. (ii) The alteration in electrophoretic mobility of
      ICP0 made in cells infected with DeltaUL13 virus was due to the absence of the
      UL13 protein and not to failure of posttranslational modification of
      Deltaalpha22/DeltaUS1.5 proteins inasmuch as the mobility of ICP0 in cells
      infected with Deltaalpha22/DeltaUS1.5 virus could not be differentiated from that
      of wild-type infected cells. (iii) ICP0 is extensively phosphorylated in infected
      cells even in the absence of UL13 protein. ICP0 is, however, a substrate for the
      UL13 kinase inasmuch as ICP0 was phosphorylated in mixtures of immune complexes
      of ICP0 and UL13. Complexes containing ICP0 only or infected cell lysate proteins
      reacting with preimmune serum from the rabbit immunized with UL13 protein failed
      to phosphorylate ICP0. (iv) In the absence of UL13, ICP22 is overproduced-an
      imbalance attributed to UL13. Thus, ICP22 regulates both the utilization of
      splice acceptor sites and the longevity of ICP0 mRNA (K. L. Carter and B.
      Roizman, 1996, Proc. Natl. Acad. Sci. USA 93, 12535-12540); UL13 is involved in
      the posttranslational modification of ICP0 and is required for both
      posttranslational processing and control of abundance of ICP22.

PMID- 9281522
TI  - Completion of the Lassa fever virus sequence and identification of a RING finger
      open reading frame at the L RNA 5' End.
AB  - Lassa (LAS) fever virus is a highly pathogenic arenavirus with large (L) and
      small (S) RNA genomic segments. The 5' end of the LAS L segment is described
      here, thereby completing the sequence of the most virulent arenavirus analyzed to
      date. In keeping with the ambisense gene structure of the arenaviruses, the LAS L
      RNA encodes a 250-kDa protein and an 11-kDa protein in opposite senses with
      respect to each other. The 11-kDa protein, defined previously in arenaviruses
      lymphocytic choriomeningitis (LCM), Tacaribe (TAC), and Pichinde (PIC), contains
      a RING type of zinc-binding structure. Expression of the 11-kDa protein in LAS
      virus-infected cells has been confirmed by binding to peptide-specific antibody.

PMID- 9281520
TI  - Use of herpes simplex virus thymidine kinase to improve the antiviral activity of
      zidovudine.
AB  - Many antiviral drugs must be metabolized to their active form by cellular
      enzymes. Their antiviral activity may therefore be limited by an inefficient
      metabolism, leading to low intracellular concentration of the active form or to
      the accumulation of toxic intermediate metabolites. Gene transfer might be used
      to overcome such limitations by transducing a gene able to increase intracellular
      drug metabolism. To prove such a concept, we chose the well-studied paradigm of
      zidovudine (AZT) metabolism and anti-HIV activity. AZT-triphosphate is the active
      form of AZT, acting through inhibition of HIV reverse transcription. In human
      cells, the rate-limiting step for AZT phosphorylation is catalyzed by the
      thymidylate kinase. We thus tested the capacity of herpes simplex virus type 1
      thymidine kinase, which possesses a thymidylate kinase activity, to improve AZT
      metabolism and antiviral activity. Our results show enhanced AZT phosphorylation
      in HSV-1 TK-expressing lymphoid and monoblastoid cells, which correlated with
      significantly improved antiviral activity against different strains of HIV-1. The
      antiviral activity of Foscarnet, another reverse transcriptase inhibitor that
      does not require phosphorylation, remained unchanged. These results suggest that
      gene transfer might be envisioned for genetic pharmacomodulation of antiviral
      drugs.

PMID- 9281523
TI  - L-Selectin--a signalling receptor for lipopolysaccharide.
AB  - The activation of leukocytes by bacterial cell-wall lipopolysaccharide
      contributes to the pathogenesis of septic shock. We propose that in neutrophils,
      and possibly other leukocytes, L-selectin can act as a low-affinity
      lipopolysaccharide receptor. Inhibitors of L-selectin may therefore be of
      therapeutic value in treating this life-threatening condition.

PMID- 9281524
TI  - On the pairing rules for recognition in the minor groove of DNA by pyrrole
      imidazole polyamides.
AB  - BACKGROUND: Cell-permeable small molecules that target predetermined DNA
      sequences with high affinity and specificity have the potential to control gene
      expression. A binary code has been developed to correlate DNA sequence with side
      by-side pairings between N-methylpyrrole (Py) and N-methylimidazole (Im)
      carboxamides in the DNA minor groove. We set out to determine the relative
      energetics of pairings of Im/Py, Py/Im, Im/Im, and Py/Py for targeting G.C and
      A.T base pairs. A key specificity issue, which has not been previously addressed,
      is whether an Im/Im pair is energetically equivalent to an Im/Py pair for
      targeting G.C base pairs. RESULTS: Equilibrium association constants were
      determined at two five-base-pair sites for a series of four six-ring hairpin
      polyamides, in order to test the relative energetics of the four aromatic amino
      acid pairings opposite G.C and A.T base pairs in the central position. We
      observed that a G.C base pair was effectively targeted with Im/Py but not Py/Im,
      Py/Py, or Im/Im. The A.T base pair was effectively targeted with Py/Py but not
      Im/Py, Py/Im, or Im/Im. CONCLUSIONS: An Im/Im pairing is energetically disfavored
      for the recognition of both A.T and G.C. This specificity will create important
      limitations on undesirable slipped motifs that are available for unlinked dimers
      in the minor groove. Baseline energetic parameters will thus be created which,
      using the predictability of the current pairing rules for specific molecular
      recognition of double-helical DNA, will guide further second-generation polyamide
      design for DNA recognition.

PMID- 9281525
TI  - Surprising fidelity of template-directed chemical ligation of oligonucleotides.
AB  - BACKGROUND: Nucleic acid replication via oligonucleotide ligation has been shown
      to be extremely prone to errors. If this is the case, it is difficult to envision
      how the assembly and replication of short oligonucleotides could have contributed
      to the origin of life and to the evolution of a putative RNA world. In order to
      assess the fidelity of oligonucleotide replication more accurately, chemical
      ligation reactions were performed with constant-sequence DNA templates and random
      sequence DNA pools as substrates. RESULTS: In keeping with earlier results,
      constant-sequence hairpin templates were not faithfully copied by random-sequence
      substrates. Linear templates, however, showed exceptional replication fidelity,
      particularly when random hexamers were ligated at 25 degrees C. Surprisingly, at
      low temperatures the formation of G.A base pairs was common and sometimes
      occurred even more readily than the formation of the corresponding Watson-Crick A
      T and G-C base pairs. CONCLUSIONS: The fidelity of ligation reactions increases
      with temperature and decreases with the length of the random-sequence substrates.
      Oligonucleotides with a defined sequence can be copied faithfully in the absence
      of enzymes. Thus, to the extent that short oligonucleotides could readily have
      been generated by prebiotic mechanisms, it is possible that the earliest self
      replicators arose via oligonucleotide ligation.

PMID- 9281526
TI  - Evidence for the metal-cofactor independence of an RNA phosphodiester-cleaving
      DNA enzyme.
AB  - BACKGROUND: RNA and DNA are polymers that lack the diversity of chemical
      functionalities that make proteins so suited to biological catalysis. All
      naturally occurring ribozymes (RNA catalysts) that catalyze the formation,
      transfer and hydrolysis of phosphodiesters require metal-ion cofactors for their
      catalytic activity. We wished to investigate whether, and to what extent, DNA
      molecules could catalyze the cleavage (by either hydrolysis or
      transesterification) of a ribonucleotide phosphodiester in the absence of
      divalent or higher-valent metal ions or, indeed, any other cofactors. RESULTS: We
      performed in vitro selection and amplification experiments on a library of random
      sequence DNA that incorporated a single ribonucleotide, a suitable site for
      cleavage. Following 12 cycles of selection and amplification, a 'first
      generation' of DNA enzymes (DNAzymes) cleaved their internal ribonucleotide
      phosphodiesters at rates approximately 10(7)-fold faster than the spontaneous
      rate of cleavage of the dinucleotide ApA in the absence of divalent cations. Re
      selection from a partially randomized DNA pool yielded 'second generation'
      DNAzymes that self-cleaved at rates of approximately 0.01 min-1 (a 10(8)-fold
      rate enhancement over the cleavage rate of ApA). The properties of these selected
      catalysts were different in key respects from those of metal-utilizing ribozymes
      and DNAzymes. The catalyzed cleavage took place in the presence of different
      chelators and ribonuclease inhibitors. Trace-metal analysis of the reaction
      buffer (containing very high purity reagents) by inductively coupled plasma
      optical emission spectrophotometry indicated that divalent or higher-valent metal
      ions do not mediate catalysis by the DNAzymes. CONCLUSIONS: Our results indicate
      that, although ribozymes are sometimes regarded generically to be metalloenzymes,
      the nucleic acid components of ribozymes may play a substantial role in the
      overall catalysis. Given that metal cofactors increase the rate of catalysis by
      ribozymes only approximately 10(2)-10(3)-fold above that of the DNAzyme described
      in this paper, it is conceivable that substrate positioning, transition-state
      stabilization or general acid/base catalysis by the nucleic acid components of
      ribozymes and DNAzymes may contribute significantly to their overall catalytic
      performance.

PMID- 9281527
TI  - Isolation of novel ribozymes that ligate AMP-activated RNA substrates.
AB  - BACKGROUND: The protein enzymes RNA ligase and DNA ligase catalyze the ligation
      of nucleic acids via an adenosine-5'-5'-pyrophosphate 'capped' RNA or DNA
      intermediate. The activation of nucleic acid substrates by adenosine 5'
      monophosphate (AMP) may be a vestige of 'RNA world' catalysis. AMP-activated
      ligation seems ideally suited for catalysis by ribozymes (RNA enzymes), because
      an RNA motif capable of tightly and specifically binding AMP has previously been
      isolated. RESULTS: We used in vitro selection and directed evolution to explore
      the ability of ribozymes to catalyze the template-directed ligation of AMP
      activated RNAs. We subjected a pool of 10(15) RNA molecules, each consisting of
      long random sequences flanking a mutagenized adenosine triphosphate (ATP)
      aptamer, to ten rounds of in vitro selection, including three rounds involving
      mutagenic polymerase chain reaction. Selection was for the ligation of an
      oligonucleotide to the 5'-capped active pool RNA species. Many different ligase
      ribozymes were isolated; these ribozymes had rates of reaction up to 0.4
      ligations per hour, corresponding to rate accelerations of approximately 5 x10(5)
      over the templated, but otherwise uncatalyzed, background reaction rate. Three
      characterized ribozymes catalyzed the formation of 3'-5'-phosphodiester bonds and
      were highly specific for activation by AMP at the ligation site. CONCLUSIONS: The
      existence of a new class of ligase ribozymes is consistent with the hypothesis
      that the unusual mechanism of the biological ligases resulted from a conservation
      of mechanism during an evolutionary replacement of a primordial ribozyme ligase
      by a more modern protein enzyme. The newly isolated ligase ribozymes may also
      provide a starting point for the isolation of ribozymes that catalyze the
      polymerization of AMP-activated oligonucleotides or mononucleotides, which might
      have been the prebiotic analogs of nucleoside triphosphates.

PMID- 9281528
TI  - Copper-binding motifs in catalysis, transport, detoxification and signaling.
AB  - Copper is required for many biological processes but is toxic at high cellular
      concentrations, so levels in the cell must be strictly controlled. Copper-binding
      motifs have been identified and characterized in many proteins. The way in which
      copper is coordinated by these motifs is important for the transport and
      distribution of intracellular copper and for the effective functioning of copper
      dependent enzymes.

PMID- 9281529
TI  - An unusual pH-independent and metal-ion-independent mechanism for hairpin
      ribozyme catalysis.
AB  - BACKGROUND: Hairpin ribozymes (RNA enzymes) catalyze the same chemical reaction
      as ribonuclease A and yet RNAs do not usually have functional groups analogous to
      the catalytically essential histidine and lysine sidechains of protein
      ribonucleases. Some RNA enzymes appear to recruit metal ions to act as Lewis
      acids in charge stabilization and metal-bound hydroxide for general base
      catalysis, but it has been reported that the hairpin ribozyme functions in the
      presence of metal ion chelators. This led us to investigate whether the hairpin
      ribozyme exploits a metal-ion-independent catalytic strategy. RESULTS:
      Substitution of sulfur for nonbridging oxygens of the reactive phosphate of the
      hairpin ribozyme has small, stereospecific and metal-ion-independent effects on
      cleavage and ligation mediated by this ribozyme. Cobalt hexammine, an exchange
      inert metal complex, supports full hairpin ribozyme activity, and the ribozyme's
      catalytic rate constants display only a shallow dependence on pH. CONCLUSIONS:
      Direct metal ion coordination to phosphate oxygens is not essential for hairpin
      ribozyme catalysis and metal-bound hydroxide does not serve as the general base
      in this catalysis. Several models might account for the unusual pH and metal ion
      independence: hairpin cleavage and ligation might be limited by a slow
      conformational change; a pH-independent or metal-cation-independent chemical
      step, such as breaking the 5' oxygen-phosphorus bond, might be rate determining;
      or finally, functional groups within the ribozyme might participate directly in
      catalytic chemistry. Whichever the case, the hairpin ribozyme appears to employ a
      unique strategy for RNA catalysis.

PMID- 9281531
TI  - Subverting the cell cycle.

PMID- 9281530
TI  - Protein templates for the biosynthesis of peptide antibiotics.
AB  - Peptide synthetases of microbial origin can act as protein templates for the
      biosynthesis of unusual, often pharmacologically active, peptides of diverse
      structure and biological activity. Specific repeated modules in the synthetases
      each contain at least two distinct domains, required for substrate adenylation
      and thiolation, that define the sequence and length of the peptide product. The
      first crystal structure of an adenylation domain has provided insights into the
      mechanism of substrate recognition and activation.

PMID- 9281574
TI  - Pathways of spindle pole formation: different mechanisms; conserved components.

PMID- 9281575
TI  - Motoring to the finish: kinesin and dynein work together to orient the yeast
      mitotic spindle.

PMID- 9281576
TI  - Osmotic balance regulates cell fusion during mating in Saccharomyces cerevisiae.
AB  - Successful zygote formation during yeast mating requires cell fusion of the two
      haploid mating partners. To ensure that cells do not lyse as they remodel their
      cell wall, the fusion event is both temporally and spatially regulated: the cell
      wall is degraded only after cell-cell contact and only in the region of cell-cell
      contact. To understand how cell fusion is regulated, we identified mutants
      defective in cell fusion based upon their defect in mating to a fus1 fus2 strain
      (Chenevert, J., N. Valtz, and I. Herskowitz. 1994. Genetics 136:1287-1297). Two
      of these cell fusion mutants are defective in the FPS1 gene, which codes for a
      glycerol facilitator (Luyten, K., J. Albertyn, W.F. Skibbe, B.A. Prior, J. Ramos,
      J.M. Thevelein, and S. Hohmann. 1995. EMBO [Eur. Mol. Biol. Organ.] J. 14:1360
      1371). To determine whether inability to maintain osmotic balance accounts for
      the defect in cell fusion in these mutants, we analyzed the behavior of an
      fps1Delta mutant with reduced intracellular glycerol levels because of a defect
      in the glycerol-3-phosphate dehydrogenase (GPD1) gene (Albertyn, J., S. Hohmann,
      J.M. Thevelein, and B.A. Prior. 1994. Mol. Cell. Biol. 14:4135-4144): deletion of
      GPD1 partially suppressed the cell fusion defect of fps1 mutants. In contrast,
      overexpression of GPD1 exacerbated the defect. The fusion defect could also be
      partially suppressed by 1 M sorbitol. These observations indicate that the fusion
      defect of fps1 mutants results from inability to regulate osmotic balance and
      provide evidence that the osmotic state of the cell can regulate fusion. We have
      also observed that mutants expressing hyperactive protein kinase C exhibit a cell
      fusion defect similar to that of fps1 mutants. We propose that Pkc1p regulates
      cell fusion in response to osmotic disequilibrium. Unlike fps1 mutants, fus1 and
      fus2 mutants are not influenced by expression of GPD1 or by 1 M sorbitol. Their
      fusion defect is thus unlikely to result from altered osmotic balance.

PMID- 9281577
TI  - Structure of L-A virus: a specialized compartment for the transcription and
      replication of double-stranded RNA.
AB  - The genomes of double-stranded (ds)RNA viruses are never exposed to the cytoplasm
      but are confined to and replicated from a specialized protein-bound compartment
      the viral capsid. We have used cryoelectron microscopy and three-dimensional
      image reconstruction to study this compartment in the case of L-A, a yeast virus
      whose capsid consists of 60 asymmetric dimers of Gag protein (76 kD). At 16-A
      resolution, we distinguish multiple domains in the elongated Gag subunits, whose
      nonequivalent packing is reflected in subtly different morphologies of the two
      protomers. Small holes, 10-15 A across, perforate the capsid wall, which
      functions as a molecular sieve, allowing the exit of transcripts and the influx
      of metabolites, while retaining dsRNA and excluding degradative enzymes. Scanning
      transmission electron microscope measurements of mass-per-unit length suggest
      that L-A RNA is an A-form duplex, and that RNA filaments emanating from disrupted
      virions often consist of two or more closely associated duplexes. Nuclease
      protection experiments confirm that the genome is entirely sequestered inside
      full capsids, but it is packed relatively loosely; in L-A, the center-to-center
      spacing between duplexes is 40-45 A, compared with 25-30 A in other double
      stranded viruses. The looser packing of L-A RNA allows for maneuverability in the
      crowded capsid interior, in which the genome (in both replication and
      transcription) must be translocated sequentially past the polymerase immobilized
      on the inner capsid wall.

PMID- 9281578
TI  - Dynamics of ATP-induced calcium signaling in single mouse thymocytes.
AB  - Extracellular ATP (ATPo) elicits a robust change in the concentration of
      intracellular Ca2+ ([Ca2+]i) in fura-2-loaded mouse thymocytes. Most thymocytes
      (60%) exposed to ATPo exhibited a biphasic rise in [Ca2+]i; [Ca2+]i rose slowly
      at first to a mean value of 260 nM after 163 s and then increased rapidly to a
      peak level of 735 nM. In many cells, a declining plateau, which lasted for more
      than 10 min, followed the crest in [Ca2+]i. Experiments performed in the absence
      of extracellular [Ca2+]o abolished the rise in thymocyte [Ca2+]i, indicating that
      Ca2+ influx, rather than the release of stored Ca2+, is stimulated by ATPo. ATPo-
      mediated Ca2+ influx was potentiated as the [Mg2+]o was reduced, confirming that
      ATP4- is the active agonist form. In the absence of Mg2+o, 3'-O-(4
      benzoyl)benzoyl-ATP (BzATP) proved to be the most effective agonist of those
      tested. The rank order of potency for adenine nucleotides was BzATP4->ATP4
      >MgATP2->ADP3-, suggesting purinoreceptors of the P2X7/P2Z class mediate the ATPo
      response. Phenotyping experiments illustrate that both immature (CD4-CD8-,
      CD4+CD8+) and mature (CD4+CD8-, CD4-CD8+) thymocyte populations respond to ATP.
      Further separation of the double-positive population by size revealed that the
      ATPo-mediated [Ca2+]i response was much more pronounced in large (actively
      dividing) than in small (terminally differentiated) CD4+CD8+ thymocytes. We
      conclude that thymocytes vary in sensitivity to ATPo depending upon the degree of
      maturation and suggest that ATPo may be involved in processes that control
      cellular differentiation within the thymus.

PMID- 9281579
TI  - Kinesin- and myosin-driven steps of vesicle recruitment for Ca2+-regulated
      exocytosis.
AB  - Kinesin and myosin have been proposed to transport intracellular organelles and
      vesicles to the cell periphery in several cell systems. However, there has been
      little direct observation of the role of these motor proteins in the delivery of
      vesicles during regulated exocytosis in intact cells. Using a confocal
      microscope, we triggered local bursts of Ca2+-regulated exocytosis by wounding
      the cell membrane and visualized the resulting individual exocytotic events in
      real time. Different temporal phases of the exocytosis burst were distinguished
      by their sensitivities to reagents targeting different motor proteins. The
      function blocking antikinesin antibody SUK4 as well as the stalk-tail fragment of
      kinesin heavy chain specifically inhibited a slow phase, while butanedione
      monoxime, a myosin ATPase inhibitor, inhibited both the slow and fast phases. The
      blockage of Ca2+/calmodulin-dependent protein kinase II with autoinhibitory
      peptide also inhibited the slow and fast phases, consistent with disruption of a
      myosin-actin- dependent step of vesicle recruitment. Membrane resealing after
      wounding was also inhibited by these reagents. Our direct observations provide
      evidence that in intact living cells, kinesin and myosin motors may mediate two
      sequential transport steps that recruit vesicles to the release sites of Ca2+
      regulated exocytosis, although the identity of the responsible myosin isoform is
      not yet known. They also indicate the existence of three semistable vesicular
      pools along this regulated membrane trafficking pathway. In addition, our results
      provide in vivo evidence for the cargo-binding function of the kinesin heavy
      chain tail domain.

PMID- 9281580
TI  - Heterotrimeric kinesin-II is required for the assembly of motile 9+2 ciliary
      axonemes on sea urchin embryos.
AB  - Heterotrimeric kinesin-II is a plus end- directed microtubule (MT) motor protein
      consisting of distinct heterodimerized motor subunits associated with an
      accessory subunit. To probe the intracellular transport functions of kinesin-II,
      we microinjected fertilized sea urchin eggs with an anti-kinesin-II monoclonal
      antibody, and we observed a dramatic inhibition of ciliogenesis at the blastula
      stage characterized by the assembly of short, paralyzed, 9+0 ciliary axonemes
      that lack central pair MTs. Control embryos show no such defect and form swimming
      blastulae with normal, motile, 9+2 cilia that contain kinesin-II as detected by
      Western blotting. Injection of anti-kinesin-II into one blastomere of a two-cell
      embryo leads to the development of chimeric blastulae covered on one side with
      short, paralyzed cilia, and on the other with normal, beating cilia. We observed
      a unimodal length distribution of short cilia on anti-kinesin-II-injected embryos
      corresponding to the first mode of the trimodal distribution of ciliary lengths
      observed for control embryos. This short mode may represent a default ciliary
      assembly intermediate. We hypothesize that kinesin-II functions during
      ciliogenesis to deliver ciliary components that are required for elongation of
      the assembly intermediate and for formation of stable central pair MTs. Thus,
      kinesin-II plays a critical role in embryonic development by supporting the
      maturation of nascent cilia to generate long motile organelles capable of
      producing the propulsive forces required for swimming and feeding.

PMID- 9281581
TI  - Kinesin-related KIP3 of Saccharomyces cerevisiae is required for a distinct step
      in nuclear migration.
AB  - Spindle orientation and nuclear migration are crucial events in cell growth and
      differentiation of many eukaryotes. Here we show that KIP3, the sixth and final
      kinesin-related gene in Saccharomyces cerevisiae, is required for migration of
      the nucleus to the bud site in preparation for mitosis. The position of the
      nucleus in the cell and the orientation of the mitotic spindle was examined by
      microscopy of fixed cells and by time-lapse microscopy of individual live cells.
      Mutations in KIP3 and in the dynein heavy chain gene defined two distinct phases
      of nuclear migration: a KIP3-dependent movement of the nucleus toward the
      incipient bud site and a dynein-dependent translocation of the nucleus through
      the bud neck during anaphase. Loss of KIP3 function disrupts the unidirectional
      movement of the nucleus toward the bud and mitotic spindle orientation, causing
      large oscillations in nuclear position. The oscillatory motions sometimes brought
      the nucleus in close proximity to the bud neck, possibly accounting for the
      viability of a kip3 null mutant. The kip3 null mutant exhibits normal
      translocation of the nucleus through the neck and normal spindle pole separation
      kinetics during anaphase. Simultaneous loss of KIP3 and kinesin-related KAR3
      function, or of KIP3 and dynein function, is lethal but does not block any
      additional detectable movement. This suggests that the lethality is due to the
      combination of sequential and possibly overlapping defects. Epitope-tagged Kip3p
      localizes to astral and central spindle microtubules and is also present
      throughout the cytoplasm and nucleus.

PMID- 9281582
TI  - Mitotic spindle positioning in Saccharomyces cerevisiae is accomplished by
      antagonistically acting microtubule motor proteins.
AB  - Proper positioning of the mitotic spindle is often essential for cell division
      and differentiation processes. The asymmetric cell division characteristic of
      budding yeast, Saccharomyces cerevisiae, requires that the spindle be positioned
      at the mother-bud neck and oriented along the mother-bud axis. The single dynein
      motor encoded by the S. cerevisiae genome performs an important but nonessential
      spindle-positioning role. We demonstrate that kinesin-related Kip3p makes a major
      contribution to spindle positioning in the absence of dynein. The elimination of
      Kip3p function in dyn1Delta cells severely compromised spindle movement to the
      mother-bud neck. In dyn1Delta cells that had completed positioning, elimination
      of Kip3p function caused spindles to mislocalize to distal positions in mother
      cell bodies. We also demonstrate that the spindle-positioning defects exhibited
      by dyn1 kip3 cells are caused, to a large extent, by the actions of kinesin-
      related Kip2p. Microtubules in kip2Delta cells were shorter and more sensitive to
      benomyl than wild-type, in contrast to the longer and benomyl-resistant
      microtubules found in dyn1Delta and kip3Delta cells. Most significantly, the
      deletion of KIP2 greatly suppressed the spindle localization defect and slow
      growth exhibited by dyn1 kip3 cells. Likewise, induced expression of KIP2 caused
      spindles to mislocalize in cells deficient for dynein and Kip3p. Our findings
      indicate that Kip2p participates in normal spindle positioning but antagonizes a
      positioning mechanism acting in dyn1 kip3 cells. The observation that deletion of
      KIP2 could also suppress the inviability of dyn1Delta kar3Delta cells suggests
      that kinesin-related Kar3p also contributes to spindle positioning.

PMID- 9281583
TI  - Mitotic spindle poles are organized by structural and motor proteins in addition
      to centrosomes.
AB  - The focusing of microtubules into mitotic spindle poles in vertebrate somatic
      cells has been assumed to be the consequence of their nucleation from
      centrosomes. Contrary to this simple view, in this article we show that an
      antibody recognizing the light intermediate chain of cytoplasmic dynein (70.1)
      disrupts both the focused organization of microtubule minus ends and the
      localization of the nuclear mitotic apparatus protein at spindle poles when
      injected into cultured cells during metaphase, despite the presence of
      centrosomes. Examination of the effects of this dynein-specific antibody both in
      vitro using a cell-free system for mitotic aster assembly and in vivo after
      injection into cultured cells reveals that in addition to its direct effect on
      cytoplasmic dynein this antibody reduces the efficiency with which dynactin
      associates with microtubules, indicating that the antibody perturbs the
      cooperative binding of dynein and dynactin to microtubules during spindle/aster
      assembly. These results indicate that microtubule minus ends are focused into
      spindle poles in vertebrate somatic cells through a mechanism that involves
      contributions from both centrosomes and structural and microtubule motor
      proteins. Furthermore, these findings, together with the recent observation that
      cytoplasmic dynein is required for the formation and maintenance of acentrosomal
      spindle poles in extracts prepared from Xenopus eggs (Heald, R., R. Tournebize,
      T. Blank, R. Sandaltzopoulos, P. Becker, A. Hyman, and E. Karsenti. 1996. Nature
      (Lond.). 382: 420-425) demonstrate that there is a common mechanism for focusing
      free microtubule minus ends in both centrosomal and acentrosomal spindles. We
      discuss these observations in the context of a search-capture-focus model for
      spindle assembly.

PMID- 9281584
TI  - Domains of neuronal microtubule-associated proteins and flexural rigidity of
      microtubules.
AB  - Microtubules are flexible polymers whose mechanical properties are an important
      factor in the determination of cell architecture and function. It has been
      proposed that the two most prominent neuronal microtubule-associated proteins
      (MAPs), tau and MAP2, whose microtubule binding regions are largely homologous,
      make an important contribution to the formation and maintenance of neuronal
      processes, putatively by increasing the rigidity of microtubules. Using optical
      tweezers to manipulate single microtubules, we have measured their flexural
      rigidity in the presence of various constructs of tau and MAP2c. The results show
      a three- or fourfold increase of microtubule rigidity in the presence of wild
      type tau or MAP2c, respectively. Unexpectedly, even low concentrations of MAPs
      promote a substantial increase in microtubule rigidity. Thus at approximately 20%
      saturation with full-length tau, a microtubule exhibits >80% of the rigidity
      observed at near saturating concentrations. Several different constructs of tau
      or MAP2 were used to determine the relative contribution of certain subdomains in
      the microtubule-binding region. All constructs tested increase microtubule
      rigidity, albeit to different extents. Thus, the repeat domains alone increase
      microtubule rigidity only marginally, whereas the domains flanking the repeats
      make a significant contribution. Overall, there is an excellent correlation
      between the strength of binding of a MAP construct to microtubules (as
      represented by its dissociation constant Kd) and the increase in microtubule
      rigidity. These findings demonstrate that neuronal MAPs as well as constructs
      derived from them increase microtubule rigidity, and that the changes in rigidity
      observed with different constructs correlate well with other biochemical and
      physiological parameters.

PMID- 9281585
TI  - Transport and localization elements in myelin basic protein mRNA.
AB  - Myelin basic protein (MBP) mRNA is localized to myelin produced by
      oligodendrocytes of the central nervous system. MBP mRNA microinjected into
      oligodendrocytes in primary culture is assembled into granules in the perikaryon,
      transported along the processes, and localized to the myelin compartment. In this
      work, microinjection of various deleted and chimeric RNAs was used to delineate
      regions in MBP mRNA that are required for transport and localization in
      oligodendrocytes. The results indicate that transport requires a 21-nucleotide
      sequence, termed the RNA transport signal (RTS), in the 3' UTR of MBP mRNA.
      Homologous sequences are present in several other localized mRNAs, suggesting
      that the RTS represents a general transport signal in a variety of different cell
      types. Insertion of the RTS from MBP mRNA into nontransported mRNAs, causes the
      RNA to be transported to the oligodendrocyte processes. Localization of mRNA to
      the myelin compartment requires an additional element, termed the RNA
      localization region (RLR), contained between nucleotide 1,130 and 1, 473 in the
      3' UTR of MBP mRNA. Computer analysis predicts that this region contains a stable
      secondary structure. If the coding region of the mRNA is deleted, the RLR is no
      longer required for localization, and the region between nucleotide 667 and 953,
      containing the RTS, is sufficient for both RNA transport and localization. Thus,
      localization of coding RNA is RLR dependent, and localization of noncoding RNA is
      RLR independent, suggesting that they are localized by different pathways.

PMID- 9281586
TI  - Nerve growth factor-specific regulation of protein methylation during neuronal
      differentiation of PC12 cells.
AB  - Protein methylation is a posttranslational modification that can potentially
      regulate signal transduction pathways in a similar manner as protein
      phosphorylation. The role of protein methylation in NGF signaling was examined by
      metabolic labeling of PC12 cell proteins with L-[methyl-3H]methionine and by in
      vitro labeling of cell proteins with L-[methyl-3H]S-adenosylmethionine. Effects
      of NGF were detected within 15 min. Methyl-labeled proteins were resolved by one
      and two dimensional SDS-PAGE. NGF affected the methylation of several 68-60-kD
      proteins (pI 5.8-6.4) and 50-kD proteins (isoelectric point pH 6.7-6.8 and 5.8
      6.2). Several NGF-induced changes in methylation increased over several hours and
      through 4 d. Moreover, methyl labeling of several specific proteins was only
      detected after NGF treatment, but not in nontreated controls. The effects of NGF
      on protein methylation were NGF specific since they were not observed with EGF or
      insulin. A requirement for protein methylation for neurite outgrowth was
      substantiated with either of two methylation inhibitors: dihydroxycyclopentenyl
      adenine (DHCA) and homocysteine. DHCA, the more potent of the two, markedly
      inhibits protein methylation and neurite outgrowth without affecting cell growth,
      NGF-induced survival, cell flattening, or several protein phosphorylations that
      are associated with early signaling events. Removal of DHCA leads to rapid
      protein methylation of several proteins and concurrent neurite outgrowth. The
      results indicate that NGF regulates the methylation of several specific proteins
      and that protein methylation is involved in neurite outgrowth from PC12 cells.

PMID- 9281588
TI  - Vascular bed-specific expression of an endothelial cell gene is programmed by the
      tissue microenvironment.
AB  - The endothelium is morphologically and functionally adapted to meet the unique
      demands of the underlying tissue. At the present time, little is known about the
      molecular basis of endothelial cell diversity. As one approach to this problem,
      we have chosen to study the mechanisms that govern differential expression of the
      endothelial cell-restricted von Willebrand factor (vWF) gene. Transgenic mice
      were generated with a fragment of the vWF gene containing 2,182 bp of 5' flanking
      sequence, the first exon and first intron coupled to the LacZ reporter gene. In
      multiple independent lines of mice, beta-galactosidase expression was detected
      within endothelial cells in the brain, heart, and skeletal muscle. In isogeneic
      transplantation models, LacZ expression in host-derived auricular blood vessels
      was specifically induced by the microenvironment of the heart. In in vitro
      coculture assays, expression of both the transgene and the endogenous vWF gene in
      cardiac microvascular endothelial cells (CMEC) was upregulated in the presence of
      cardiac myocytes. In contrast, endothelial cell levels of thrombomodulin protein
      and mRNA were unchanged by the addition of ventricular myocytes. Moreover, CMEC
      expression of vWF was not influenced by the addition of 3T3 fibroblasts or mouse
      hepatocytes. Taken together, the results suggest that the vWF gene is regulated
      by vascular bed-specific pathways in response to signals derived from the local
      microenvironment.

PMID- 9281587
TI  - A dual-specificity phosphatase Cdc25B is an unstable protein and triggers
      p34(cdc2)/cyclin B activation in hamster BHK21 cells arrested with hydroxyurea.
AB  - By incubating at 30 degrees C in the presence of an energy source,
      p34(cdc2)/cyclin B was activated in the extract prepared from a temperature
      sensitive mutant, tsBN2, which prematurely enters mitosis at 40 degrees C, the
      nonpermissive temperature (Nishimoto, T. , E. Eilen, and C. Basilico. 1978. Cell.
      15:475-483), and wild-type cells of the hamster BHK21 cell line arrested in S
      phase, without protein synthesis. Such an in vitro activation of p34(cdc2)/cyclin
      B, however, did not occur in the extract prepared from cells pretreated with
      protein synthesis inhibitor cycloheximide, although this extract still retained
      the ability to inhibit p34(cdc2)/cyclin B activation. When tsBN2 cells arrested
      in S phase were incubated at 40 degrees C in the presence of cycloheximide,
      Cdc25B, but not Cdc25A and C, among a family of dual-specificity phosphatases,
      Cdc25, was lost coincidentally with the lack of the activation of
      p34(cdc2)/cyclin B. Consistently, the immunodepletion of Cdc25B from the extract
      inhibited the activation of p34(cdc2)/cyclin B. Cdc25B was found to be unstable
      (half-life < 30 min). Cdc25B, but not Cdc25C, immunoprecipitated from the extract
      directly activated the p34(cdc2)/cyclin B of cycloheximide-treated cells as well
      as that of nontreated cells, although Cdc25C immunoprecipitated from the extract
      of mitotic cells activated the p34(cdc2)/cyclin B within the extract of
      cycloheximide-treated cells. Our data suggest that Cdc25B made an initial
      activation of p34(cdc2)/cyclin B, which initiates mitosis through the activation
      of Cdc25C.

PMID- 9281589
TI  - Fibroblast growth factor 4 directs gap junction expression in the mesenchyme of
      the vertebrate limb Bud.
AB  - Pattern in the developing limb depends on signaling by polarizing region
      mesenchyme cells, which are located at the posterior margin of the bud tip. Here
      we address the underlying cellular mechanisms. We show in the intact bud that
      connexin 43 (Cx43) and Cx32 gap junctions are at higher density between distal
      posterior mesenchyme cells at the tip of the bud than between either distal
      anterior or proximal mesenchyme cells. These gradients disappear when the apical
      ectodermal ridge (AER) is removed. Fibroblast growth factor 4 (FGF4) produced by
      posterior AER cells controls signaling by polarizing cells. We find that FGF4
      doubles gap junction density and substantially improves functional coupling
      between cultured posterior mesenchyme cells. FGF4 has no effect on cultured
      anterior mesenchyme, suggesting that any effects of FGF4 on responding anterior
      mesenchyme cells are not mediated by a change in gap junction density or
      functional communication through gap junctions. In condensing mesenchyme cells,
      connexin expression is not affected by FGF4. We show that posterior mesenchyme
      cells maintained in FGF4 under conditions that increase functional coupling
      maintain polarizing activity at in vivo levels. Without FGF4, polarizing activity
      is reduced and the signaling mechanism changes. We conclude that FGF4 regulation
      of cell-cell communication and polarizing signaling are intimately connected.

PMID- 9281590
TI  - Nuclear-cytoplasmic shuttling of the focal contact protein, zyxin: a potential
      mechanism for communication between sites of cell adhesion and the nucleus.
AB  - Integrin-dependent cell adhesion to specific extracellular matrix molecules has
      been demonstrated to trigger dramatic changes in gene expression that can affect
      cell fate. However, little is understood about the molecular mechanism by which
      events at sites of cell- substratum adhesion are communicated to the cell
      interior to regulate the transcriptional apparatus. By analogy to classical
      mechanisms of cell surface receptor function, it seems likely that some
      components of the integrin-activated signal transduction machinery will be
      colocalized with cell adhesion molecules. Zyxin is a low abundance phosphoprotein
      that accumulates with integrins at sites of cell-substratum attachment. Here we
      show that zyxin exhibits a functional nuclear export signal that is required to
      keep zyxin concentrated in the cytoplasm and is sufficient to direct nuclear
      proteins to the cytosol. Furthermore, we demonstrate that native zyxin shuttles
      between the nucleus and sites of cell adhesion in fibroblasts and is thus an
      excellent candidate for relaying information between these two compartments.

PMID- 9281591
TI  - ICAP-1, a novel beta1 integrin cytoplasmic domain-associated protein, binds to a
      conserved and functionally important NPXY sequence motif of beta1 integrin.
AB  - The cytoplasmic domains of integrins are essential for cell adhesion. We report
      identification of a novel protein, ICAP-1 (integrin cytoplasmic domain-
      associated protein-1), which binds to the 1 integrin cytoplasmic domain. The
      interaction between ICAP-1 and beta1 integrins is highly specific, as
      demonstrated by the lack of interaction between ICAP-1 and the cytoplasmic
      domains of other beta integrins, and requires a conserved and functionally
      important NPXY sequence motif found in the COOH-terminal region of the beta1
      integrin cytoplasmic domain. Mutational studies reveal that Asn and Tyr of the
      NPXY motif and a Val residue located NH2-terminal to this motif are critical for
      the ICAP-1 binding. Two isoforms of ICAP-1, a 200-amino acid protein (ICAP
      1alpha) and a shorter 150-amino acid protein (ICAP-1beta), derived from
      alternatively spliced mRNA, are expressed in most cells. ICAP-1alpha is a
      phosphoprotein and the extent of its phosphorylation is regulated by the cell
      matrix interaction. First, an enhancement of ICAP-1alpha phosphorylation is
      observed when cells were plated on fibronectin-coated but not on nonspecific poly
      L-lysine-coated surface. Second, the expression of a constitutively activated
      RhoA protein that disrupts the cell-matrix interaction results in
      dephosphorylation of ICAP-1alpha. The regulation of ICAP-1alpha phosphorylation
      by the cell-matrix interaction suggests an important role of ICAP-1 during
      integrin-dependent cell adhesion.

PMID- 9281592
TI  - Integrin alpha2beta1 is a receptor for the cartilage matrix protein
      chondroadherin.
AB  - Chondroadherin (the 36-kD protein) is a leucine-rich, cartilage matrix protein
      known to mediate adhesion of isolated chondrocytes. In the present study we
      investigated cell surface proteins involved in the interaction of cells with
      chondroadherin in cell adhesion and by affinity purification. Adhesion of bovine
      articular chondrocytes to chondroadherin-coated dishes was dependent on Mg2+ or
      Mn2+ but not Ca2+. Adhesion was partially inhibited by an antibody recognizing
      beta1 integrin subunit. Chondroadherin-binding proteins from chondrocyte lysates
      were affinity purified on chondroadherin-Sepharose. The beta1 integrin antibody
      immunoprecipitated two proteins with molecular mass approximately 110 and 140 kD
      (nonreduced) from the EDTA-eluted material. These results indicate that a beta1
      integrin on chondrocytes interacts with chondroadherin. To identify the alpha
      integrin subunit(s) involved in interaction of cells with the protein, we
      affinity purified chondroadherin-binding membrane proteins from human
      fibroblasts. Immunoprecipitation of the EDTA-eluted material from the affinity
      column identified alpha2beta1 as a chondroadherin-binding integrin. These results
      are in agreement with cell adhesion experiments where antibodies against the
      integrin subunit alpha2 partially inhibited adhesion of human fibroblast and
      human chondrocytes to chondroadherin. Since alpha2beta1 also is a receptor for
      collagen type II, we tested the ability of different antibodies against the
      alpha2 subunit to inhibit adhesion of T47D cells to collagen type II and
      chondroadherin. The results suggested that adhesion to collagen type II and
      chondroadherin involves similar or nearby sites on the alpha2beta1 integrin.
      Although alpha2beta1 is a receptor for both collagen type II and chondroadherin,
      only adhesion of cells to collagen type II was found to mediate spreading.

PMID- 9281594
TI  - Molecular cloning and pharmacological characterization of a new galanin receptor
      subtype.
AB  - Galanin, a 29-30-amino acid neuropeptide, is widely distributed in central and
      peripheral systems and mediates a variety of physiological functions.
      Pharmacological studies have suggested the existence of multiple receptor
      subtypes but only the type I (GalR1) galanin receptor has been cloned. Now we
      report the cloning by a combination of sib selection and rapid amplification of
      cDNA ends of a cDNA encoding a new galanin receptor (GalR2) from rat
      hypothalamus. The receptor is 372 amino acids in length and shares only 40%
      homology with the rat GalR1 receptor. It contains seven putative transmembrane
      domains with the amino and carboxyl termini being least identical to GalR1.
      Northern blot analyses revealed a 2-kilobase pair mRNA species distributed in
      several tissues, suggesting a broader functional spectrum than GalR1. 125I
      Labeled human galanin binding to rat GalR2 receptor expressed in COS-1 cells was
      saturable (Kd = 0.59 nM) and could be displaced by galanin, several galanin
      fragments, and chimeric peptides. The pharmacological profiles of GalR1 and GalR2
      receptors were distinguishable by galanin fragment(2-29), which bound the cloned
      GalR2 receptor with markedly higher affinity than the GalR1 receptor. Activation
      of the cloned receptor by galanin led to inhibition of forskolin-stimulated
      intracellular cAMP production. The cloning of this new receptor subtype should
      provide further insights into the mechanisms by which galanin mediates its
      diverse physiological functions. The identification of galanin(2-29) as a
      receptor-specific ligand should enhance the understanding of specificity of
      galanin-receptor interactions.

PMID- 9281593
TI  - The kinetics of L-selectin tethers and the mechanics of selectin-mediated
      rolling.
AB  - Two mechanisms have been proposed for regulating rolling velocities on selectins.
      These are (a) the intrinsic kinetics of bond dissociation, and (b) the reactive
      compliance, i.e., the susceptibility of the bond dissociation reaction to applied
      force. To determine which of these mechanisms explains the 7.5-11.5-fold faster
      rolling of leukocytes on L-selectin than on E- and P-selectins, we have compared
      the three selectins by examining the dissociation of transient tethers. We find
      that the intrinsic kinetics for tether bond dissociation are 7-10-fold more rapid
      for L-selectin than for E- and P-selectins, and are proportional to the rolling
      velocities through these selectins. The durations of pauses during rolling
      correspond to the duration of transient tethers on low density substrates.
      Moreover, applied force increases dissociation kinetics less for L-selectin than
      for E- and P-selectins, demonstrating that reactive compliance is not responsible
      for the faster rolling through L-selectin. Further measurements provide a
      biochemical and biophysical framework for understanding the molecular basis of
      rolling. Displacements of tethered cells during flow reversal, and measurements
      of the distance between successive pauses during rolling provide estimates of the
      length of a tether and the length of the adhesive contact zone, and suggest that
      rolling occurs with as few as two tethers per contact zone. Tether bond lifetime
      is an exponential function of the force on the bond, and the upper limit for the
      tether bond spring constant is of the same order of magnitude as the estimated
      elastic spring constant of the lectin-EGF unit. Shear uniquely enhances the rate
      of L-selectin transient tether formation, and conversion of tethers to rolling
      adhesions, providing further understanding of the shear threshold requirement for
      rolling through L-selectin.

PMID- 9281595
TI  - Pharmacological characterization of the murine and human orthologs of multidrug
      resistance protein in transfected human embryonic kidney cells.
AB  - Overexpression of the human multidrug-resistance protein (MRP) causes a form of
      multidrug resistance similar to that conferred by P-glycoprotein, although the
      two proteins are only distantly related. In contrast to P-glycoprotein, human MRP
      has also been shown to be a primary active transporter of a structurally diverse
      range of organic anionic conjugates, some of which may be physiological
      substrates. At present, the mechanism by which MRP transports these compounds and
      mediates multidrug resistance is not understood. With the objective of developing
      an animal model for studies on the normal functions of MRP and its ability to
      confer multidrug resistance in vivo, we recently cloned the murine ortholog of
      MRP (mrp). To assess the degree of functional conservation between mrp and MRP,
      we directly compared the drug cross-resistance profiles they confer when
      transfected into human embryonic kidney cells, as well as their ability to
      actively transport leukotriene C4, 17beta-Estradiol 17beta-(D-glucuronide), and
      vincristine; mrp and MRP conferred similar drug resistance profiles, with the
      exception that only MRP conferred resistance to the anthracyclines tested.
      Consistent with these findings, accumulation of [3H]vincristine and [3H]VP-16 was
      decreased, and efflux of [3H]vincristine was increased in both murine and human
      MRP-transfected cell populations, whereas only human MRP-transfected cells
      displayed decreased accumulation and increased efflux of [3H]daunorubicin.
      Membrane vesicles derived from both transfected cell populations transported
      leukotriene C4 in an ATP-dependent manner with comparable efficiency, although
      the efficiency of 17beta-estradiol 17beta-(D-glucuronide) transport was somewhat
      higher with MRP transfectants. ATP-dependent transport of vincristine was also
      observed with vesicles from mrp and MRP transfectants but only in the presence of
      glutathione. These studies reveal intrinsic differences between the murine and
      human MRP orthologs with respect to their ability to confer resistance to a major
      class of chemotherapeutic drugs.

PMID- 9281596
TI  - DNA modifications by antitumor trans-[PtCl2(E-iminoether)2].
AB  - Recent findings that an analogue of clinically ineffective transplatin, trans
      [PtCl2(E-iminoether)2], exhibits antitumor activity has helped reevaluation of
      the empirical structure-antitumor activity relationship generally accepted for
      platinum(II) complexes. According to this relationship, only the cis geometry of
      leaving ligands in the bifunctional platinum(II) complexes, should be
      therapeutically active. Global modifications of natural DNAs in cell-free media
      by trans-[PtCl2(E-iminoether)2] were studied through various molecular
      biophysical methods and compared with modifications by cis-[PtCl2(E
      iminoether)2], transplatin, cisplatin, and monofunctional
      chlorodiethylenetriamineplatinum(II) chloride. Thus, the results of this study
      have extended our recent finding, indicating that the prevalent lesion occurring
      in double-helical DNA on its modification by trans-[PtCl2(E-iminoether)2] is a
      monofunctional adduct at guanine residues. The modification by trans-[PtCl2(E
      iminoether)2] has been found to induce local distortions in DNA, which have a
      character differing fundamentally from those induced by both clinically
      ineffective or antitumor platinum complexes tested in this study. The different
      character of alterations induced in DNA by the adducts of trans-[PtCl2(E
      iminoether)2] and transplatin has been suggested to be relevant to the unexpected
      observation that the new complex with leaving chloride groups in trans position
      exhibits antitumor efficacy. In addition, the results support the idea that
      platinum drugs that bind to DNA in a manner fundamentally different from that of
      cisplatin can exhibit altered biological properties, including differing spectra
      and intensities of antitumor activity.

PMID- 9281597
TI  - Developmentally regulated expression of the CYP4A genes in the spontaneously
      hypertensive rat kidney.
AB  - The CYP4A enzymes catalyze the formation of 20-hydroxyeicosatetraenoic acid (20
      HETE), which has potent effects on the renal vasculature and tubular ion
      transport. Based on an increased 20-HETE formation in renal microsomes from
      spontaneously hypertensive rats, it has been proposed that increased expression
      of the CYP4A genes is an early event in the development of hypertension in these
      animals. To test this hypothesis, we developed RNase protection assays for
      specific detection of the individual CYP4A genes in the kidneys of spontaneously
      hypertensive and Wistar-Kyoto rats. Distinct age-dependent patterns of expression
      were observed for the individual CYP4A genes, with only CYP4A3 mRNA measurable in
      the kidneys of 1-week-old rats. CYP4A1 and CYP4A8 mRNA were detectable by 3 weeks
      of age and CYP4A2 mRNA at 5 weeks of age. The expression of CYP4A1 and CYP4A3
      varied 4-5-fold throughout development and was highest between 3 and 5 weeks of
      age, declining steadily thereafter to 20% of their maximal level by 9 weeks of
      age. CYP4A2 mRNA levels increased steadily between 5 and 9 weeks of age, whereas
      CYP4A8 mRNA levels were relatively constant throughout development. The CYP4A3
      mRNA level was significantly increased 1. 6-2-fold in the cortex and outer
      medulla of 1-4-week-old spontaneously hypertensive rat kidneys relative to the
      corresponding level in the Wistar-Kyoto. A similar 1.4-1.7-fold increase in
      CYP4A8 mRNA was also found in 3- and 4-week-old spontaneously hypertensive
      kidneys. Accompanying the increased expression of CYP4A3 and CYP4A8 mRNA in the
      prehypertensive rats were corresponding changes in functional CYP4A measured as
      either arachidonic acid or lauric acid omega-hydroxylase activity (1.4-2.0-fold
      increases) and CYP4A protein levels. After 4 weeks of age, the level of CYP4A
      mRNA, enzyme activity, and protein were similar in the kidneys of Wistar-Kyoto
      and spontaneously hypertensive rats. The findings suggest that the expression of
      CYP4A3 and CYP4A8 may be critical to the early changes in eicosanoid formation
      and renal function in the young spontaneously hypertensive rat.

PMID- 9281598
TI  - Ionizing radiation and teniposide increase p21(waf1/cip1) and promote Rb
      dephosphorylation but fail to suppress E2F activity in MCF-7 breast tumor cells.
AB  - Ionizing radiation and the topoisomerase II inhibitor, teniposide (VM-26) both
      increase levels of the cyclin dependent kinase inhibitor, p21(waf1/cip1) and
      promote dephosphorylation of the retinoblastoma tumor suppressor protein, Rb, in
      MCF-7 breast tumor cells, perturbations associated with suppression of the
      activity of the transcription factor, E2F. However, studies using an E2F binding
      site-luciferase reporter plasmid transfected into MCF-7 cells failed to
      demonstrate a reduction in E2F activity in response to VM-26 or to ionizing
      radiation. In contrast, E2F activity (both basal and E1A stimulated) could be
      suppressed by transfection with a plasmid expressing Rb, indicating that the
      capacity of E2F to bind to Rb and to be inactivated by Rb is functionally intact
      in MCF-7 cells. These findings in MCF-7 breast tumor cells suggest that E2F
      activity may not be directly susceptible to modulation by endogenous
      p21(waf1/cip1) and Rb.

PMID- 9281599
TI  - Cerebellar gamma-aminobutyric acid type A receptors: pharmacological subtypes
      revealed by mutant mouse lines.
AB  - The vast molecular heterogeneity of brain gamma-aminobutyric acid type A (GABAA)
      receptors forms the basis for receptor subtyping. Using autoradiographic
      techniques, we established the characteristics of cerebellar granule cell GABAA
      receptors by comparing wild-type mice with those with a targeted disruption of
      the alpha6 subunit gene. Cerebellar granule cells of alpha6(-/-) animals have
      severe deficits in high affinity [3H]muscimol and [3H]SR 95531 binding to GABA
      sites, in agonist-insensitive [3H]Ro 15-4513 binding to benzodiazepine sites, and
      in furosemide-induced increases in tert-[35S]butylbicyclophosphorothionate
      binding to picrotoxin-sensitive convulsant sites. These observations agree with
      the known specific properties of these sites on recombinant alpha6beta2/3gamma2
      receptors. In the presence of GABA concentrations that fail to activate alpha1
      subunit-containing receptors, methyl-6,7-dimethoxy-4-ethyl-beta-carboline (30
      microM), allopregnanolone (100 nM), and Zn2+ (10 microM) are less efficacious in
      altering tert-[35S]butylbicyclophosphorothionate binding in the granule cell
      layer of the alpha6(-/-) than alpha6(+/+) animals. These data concur with the
      deficiency of the cerebellar alpha6 and delta subunit-containing receptors in the
      alpha6(-/-) animals and could also account for the decreased affinity of
      [3H]muscimol binding to alpha6(-/-) cerebellar membranes. Predicted additional
      alterations in the cerebellar receptors of the mutant mice may explain a surplus
      of methyl-6,7-dimethoxy-4-ethyl-beta-carboline-insensitive receptors in the
      alpha6(-/-) granule cell layer and an increased diazepam-sensitivity in the
      molecular layer. These changes may be adaptive consequences of altered GABAA
      receptor subunit expression patterns in response to the loss of two subunits
      (alpha and delta) from granule cells.

PMID- 9281600
TI  - The growth-promoting effect of low-density lipoprotein may Be mediated by a
      pertussis toxin-sensitive mitogen-activated protein kinase pathway.
AB  - Low-density lipoprotein (LDL) is known to be a mitogenic factor for vascular
      smooth muscle cells (VSMCs), fibroblasts, and endothelial cells. In the current
      study, we describe possible intracellular mechanisms by which LDL elicits its
      mitogenic effects. Stimulation of VSMCs with LDL resulted in a pertussis-toxin
      (PTX)-sensitive stimulation of the 44-kDa mitogen-activated protein (MAP) kinase
      (p44(mapk)) and 42-kDa MAP kinase (p42(mapk)) isoforms as well as in a PTX
      sensitive increase in intracellular free Ca2+ concentration ([Ca2+]i). Binding of
      the LDL-induced increase in [Ca2+]i to the intracellular Ca2+ chelator bis(2
      amino-5-methylphenoxy)ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester
      resulted in a 2-fold increase in the phosphorylated p44(mapk) and p42(mapk)
      isoforms but did not influence the LDL effect of VSMC DNA synthesis. PD 98059, a
      MAP kinase kinase inhibitor, remarkably attenuated the LDL-induced activation of
      MAP kinases and DNA synthesis. Treatment of normal human skin fibroblasts and
      human fibroblasts isolated from patients with familial hypercholesterolemia
      homozygote class 1 mutations, which are not able to produce the classic LDL
      receptor, resulted also in a PTX-sensitive increase in cell DNA synthesis and
      stimulation of the p44(mapk) and p42(mapk) isoforms in both cell types. These
      results demonstrate that the mitogenic effect of LDL is mediated by a PTX
      sensitive Gi-coupled receptor that is independent of its classic receptor and
      involves activation of MAP kinase isoforms. Furthermore, the mitogenic effect of
      LDL may be mediated by the activation of the MAP kinase pathway. In contrast, the
      LDL-induced increase in [Ca2+]i may be implicated in this process only in
      conjugation with other signaling components.

PMID- 9281601
TI  - Effects of aspirin on nitric oxide formation and de novo protein synthesis by
      RINm5F cells and rat islets.
AB  - Aspirin and aspirin-like drugs are the most commonly indicated agents for the
      treatment of inflammation. Mechanisms of action for these drugs, however, are not
      clearly understood. In this study, we examined the effects of aspirin on
      production of nitric oxide (NO), a proinflammatory mediator, and show that
      aspirin inhibits NO production by transformed pancreatic beta cells (RINm5F) and
      rat islets in a concentration-dependent manner with an IC50 value of
      approximately 3 mM. Therapeutic concentrations of aspirin (1-5 mM) that block NO
      production affected neither nuclear factor-kappaB activation nor inducible NO
      synthase (iNOS) mRNA transcription but potently inhibited iNOS protein expression
      by both RINm5F cells and rat islets. The effects of aspirin on islet function
      were examined by measuring glucose-stimulated insulin secretion in the presence
      of various concentrations of aspirin. Aspirin (1-5 mM) did not affect insulin
      secretion at basal or glucose-stimulated conditions, whereas higher
      concentrations of aspirin (10-20 mM) significantly increased basal insulin
      secretion. Aspirin at high concentrations of 10 and 20 mM inhibited de novo
      protein synthesis as demonstrated by inhibition of [35S]methionine incorporation
      into total islet protein and by inhibition of rabbit reticulocyte expression by
      Brome mosaic virus mRNA, suggesting that inhibition of iNOS expression at these
      high concentrations of aspirin may be due to the impairment of the translational
      machinery. These findings indicate that inhibition of iNOS expression and NO
      production may explain, in part, the beneficial effects of aspirin as an anti
      inflammatory agent at therapeutic concentrations, whereas inhibition of de novo
      protein synthesis may possibly explain clinical and side effects of aspirin in
      the inflamed tissues and organs such as stomach and kidney that may accumulate
      high concentrations of aspirin.

PMID- 9281602
TI  - Enhanced type 1alpha metabotropic glutamate receptor-stimulated phosphoinositide
      signaling after pertussis toxin treatment.
AB  - The regulation of phosphoinositide hydrolysis by the type 1alpha metabotropic
      glutamate receptor (mGluR1alpha) was investigated in stably transfected baby
      hamster kidney (BHK) cells. Incubation of the cells with L-glutamate,
      quisqualate, and 1-aminocyclopentane-1S, 3R-dicarboxylic acid resulted in a
      marked accumulation of [3H]inositol monophosphate (InsP1) and inositol-1,4,5
      trisphosphate [Ins(1,4,5)P3] mass in a time- and concentration-dependent manner.
      Pretreatment of BHK-mGluR1alpha cells with pertussis toxin [ 100 ng/ml, 24 hr]
      led to a dramatic 12-16-fold increase in the accumulation of [3H]InsP1 and a 2
      fold increase in Ins(1,4,5)P3 in the absence of added agonist. Although only very
      low levels (</=1 microM) of L-glutamate could be detected in medium taken from
      control and PTX-treated cell monolayers, the PTX-elicited effect on basal
      [3H]InsP1 was fully reversed by preincubation of cells in the presence of
      glutamic-pyruvic transaminase and pyruvate, suggesting that an increased
      sensitivity to endogenous glutamate was responsible for the apparent agonist
      independent activation of phosphoinositidase C (PIC) after PTX treatment.
      Consistent with this hypothesis, in the presence of glutamic-pyruvic
      transaminase/pyruvate, the maximal [3H]InsP1 response to quisqualate was
      increased by >/=75%, and the EC50 shifted leftward by 65-fold [-log EC50 values
      (molar), 7.26 +/- 0.23 versus 5.45 +/- 0.07; n = 4) in PTX-treated compared with
      control cells. In contrast, antagonist effects on agonist-stimulated [3H]InsP1
      responses were similar in control and PTX-treated BHK-mGluR1alpha cells. These
      changes in the concentration-effect curves for mGluR agonists are consistent with
      a model in which the receptor associates with PTX-sensitive inhibitory (Gi/o) and
      PTX-insensitive stimulatory (Gq/11) G proteins that can each influence PIC
      activity. The present observations are consistent with a dual regulation of
      mGluR1alpha-mediated PIC activity that could be fundamental in controlling the
      output of phosphoinositide-derived messengers.

PMID- 9281603
TI  - Studies of dual promoters of mouse kappa-opioid receptor gene.
AB  - Dual promoters were identified in the mouse kappa-opioid receptor (KOR) gene. The
      distal promoter was located in the 5'-upstream region of exon 1 and the proximal
      promoter was located in the first intron of this gene. The transcription
      initiation site of the proximal promoter was mapped to the -93rd nucleotide
      position from the ATG codon in a primer extension experiment. The expression of
      KOR mRNAs transcribed from these two promoters in mouse central nervous system
      and an embryonal carcinoma cell line P19 was confirmed in a ribonuclease
      protection assay. In non-neuronal tissues, only the transcripts initiated from
      the distal promoter were detected. The biological activities of these two
      promoters were determined in transient transfection of P19 cells with a series of
      reporters, each truncated at various 5'-upstream regions. It was concluded that
      the distal promoter was located between nucleotide positions -990 and -570, and
      the proximal promoter was located between nucleotide positions -330 and -93,
      relative to the translation initiation codon. The presence of dual promoters in
      the KOR gene suggested potential regulation of KOR expression by using different
      promoters.

PMID- 9281604
TI  - Aspirin inhibits tumor necrosis factoralpha gene expression in murine tissue
      macrophages.
AB  - Aspirin has been reported to inhibit the activation of nuclear factor-kappaB (NF
      kappaB) through stabilization of inhibitor kappaB (IkappaB). This observation led
      us to investigate the role of aspirin in suppressing the activation of the NF
      kappaB-regulated tumor necrosis factor-alpha (TNF-alpha) gene expression in
      primary macrophages. We now report that therapeutic doses of aspirin suppress
      lipopolysaccharide-inducible NF-kappaB binding to an NF-kappaB binding site in
      the TNF-alpha promoter, lipopolysaccharide-induced TNF-alpha mRNA accumulation,
      and protein secretion. IkappaB is also stabilized under these conditions. The
      aspirin-initiated stabilization of IkappaB, suppression of induced TNF-alpha
      mRNA, and NF-kappaB binding to the TNF-alpha promoter are blocked by pretreatment
      with pertussis toxin. These studies suggest that aspirin may exert significant
      anti-inflammatory effects by suppressing the production of macrophage-derived
      inflammatory mediators.

PMID- 9281605
TI  - Enhanced release of secreted form of Alzheimer's amyloid precursor protein from
      PC12 cells by nicotine.
AB  - There is mounting evidence indicating that overexpression or aberrant processing
      of amyloid precursor protein (betaAPP) is causally related to Alzheimer's
      disease. betaAPP is principally cleaved within the amyloid beta protein domain to
      release a large soluble ectodomain (betaAPPs) that has been known to have a wide
      range of trophic and protective functions. Activation of phospholipase C-coupled
      receptors has been shown to increase the release of betaAPPs through protein
      kinase C and calcium. Here we have examined whether nicotine can modulate the
      expression and processing of betaAPP in PC12 cells. Treatment of PC12 cells with
      nicotine increased the release of a carboxyl-terminally truncated, secreted form
      of betaAPP into the conditioned medium without affecting the expression level of
      betaAPP mRNA. The effect of nicotine on the secretion of betaAPPs is
      concentration (>50 microM)- and time (>2 hr)-dependent and attenuated by
      cotreatment with either mecamylamine, a specific nicotinic receptor antagonist,
      or EGTA, a calcium chelator, indicating calcium entry through the neuronal
      nicotinic acetylcholine receptor is essential in enhanced betaAPPs release by
      nicotine. However, nicotine did not significantly change the amyloid beta protein
      secretion from Swedish mutant betaAPP-transfected PC12 cells. These results imply
      that nicotinic receptor agonist might be beneficial in the treatment of
      Alzheimer's disease by not only supplementing the deficient cholinergic
      neurotransmission but also stimulating the release of betaAPPs.

PMID- 9281606
TI  - Inhibition of mitosis and microtubule function through direct tubulin binding by
      a novel antiproliferative naphthopyran LY290181.
AB  - The mechanism of action of a novel antiproliferative compound LY290181 [2-amino-4
      (3-pyridyl)-4H-naphtho(1,2-b)pyran-3-carbonitrile] was characterized. LY290181 is
      a potent inhibitor of cell proliferation, producing 50% inhibition of vascular
      smooth muscle, endothelial, Chinese hamster ovary, HeLa, and human
      erythroleukemia cells at concentrations of 8-40 nM. Cell cycle analysis showed
      that LY290181 caused accumulation of smooth muscle cells at the G2/M phase and
      induced mitotic arrest in Chinese hamster ovary cells and HeLa cells. At low
      concentrations (3-30 nM), LY290181 blocked transition of cells from metaphase to
      anaphase and disrupted mitotic spindle organization. At high concentrations
      (>/=100 nM), LY290181 produced a concentration-dependent loss of cytoplasmic and
      spindle microtubules. LY290181 inhibited the polymerization of purified bovine
      brain microtubule protein into microtubules, and it depolymerized preformed
      microtubules. Using tubulin-1-anilino-8-naphthalene sulfonate complex
      fluorescence, we have shown that LY290181 directly interacted with tubulin in a
      unique manner. These studies show that LY290181 induces cell growth arrest in
      prometaphase/metaphase, and tubulin appears to be its molecular target.

PMID- 9281607
TI  - Human recombinant apolipoprotein E-enriched liposomes can mimic low-density
      lipoproteins as carriers for the site-specific delivery of antitumor agents.
AB  - Progressive hypocholesterolemia is a feature associated with a number of cancers
      of different origin, and it is caused by the high expression of low-density
      lipoprotein (LDL) receptors (LDLrs) on many tumor cell types. Selective delivery
      of chemotherapeutics using LDL as a carrier has therefore been proposed, but the
      endogenous nature of LDL hampers its pharmaceutical application. In the current
      study, we explored the possibility of synthesizing liposomes that mimic LDL from
      commercially available lipids and proteins. Small unilamellar liposomes were
      created (28.9 +/- 0.9 nm) and complexed with 5.8 +/- 0.7 molecules of human
      recombinant apolipoprotein E (apoE). On intravenous injection into rats, the
      liposomes retained their aqueous core, structural integrity, and the majority of
      the preassociated apoE. [3H]Cholesteryl oleate-labeled apoE-enriched liposomes
      showed a relatively long serum half-life (>5 hr), and a low uptake by cells of
      the reticuloendothelial system was observed (<0.8% of the injected dose at 30 min
      after injection). Pretreatment of rats with 17alpha-ethinyl estradiol, which
      induces the expression of the LDLr on the liver and adrenals, led to a 2.5-fold
      accelerated serum clearance (t1/2 = 123 +/- 10 min) and a selectively increased
      uptake of liposomes by the liver (2.0-fold) and adrenals (3.8-fold). The liver
      association of the liposomes was coupled to the lysosomal uptake route, similarly
      as for LDL. In vitro studies using B16 melanoma cells showed that the liposomes
      bound exclusively to the LDLr via their apoE moiety (90,000 liposomes/cell), with
      a 14-fold higher affinity (Kd = 0.77 +/- 0.09 nM) than LDL itself. Because of
      their favorable properties, we anticipate that these apoE-enriched liposomes are
      advantageous compared with native LDL in the development of a selective LDLr
      targeted antitumor therapy.

PMID- 9281608
TI  - Short term desensitization of the A1 adenosine receptors in DDT1MF-2 cells.
AB  - Previous studies have indicated that desensitization of the A1 adenosine receptor
      (A1AR), unlike other adenosine receptor subtypes and G protein-coupled receptors,
      required prolonged exposure to agonists. We more closely studied this observation
      by focusing on changes in the A1AR signal transduction pathway after short term
      agonist exposure (0.5-4 hr) in the hamster vas deferens smooth muscle cell line
      (DDT1MF-2 cells). Incubation of these cells with 1 microM (R)
      phenylisopropyladenosine [(R)-PIA] produced a time-dependent loss in binding of
      the agonist radioligand [125I]N6-2-(4-amino-3-iodophenyl)ethyladenosine but not
      of the antagonist radioligand [3H]8-cyclopentyl-1,3-dipropylxanthine. This was
      accompanied by a reduction in the high affinity (G protein-coupled) state of this
      receptor from 63 +/- 8% to 37 +/- 12% after treatment for 4 hr. Moreover, cells
      treated with (R)-PIA demonstrated reduced agonist-stimulated GTPase activity and
      diminished inhibition of adenylyl cyclase activity but no change in expression of
      alphai and beta subunits. The decreases in agonist binding in the desensitized
      cells were reversible after treatment of DDT1MF-2 cell membranes with alkaline
      phosphatase or protein phosphatases 1 and 2A, suggesting a role of
      phosphorylation in the uncoupling and desensitization of the A1AR. Incubation of
      cells with (R)-PIA led to rapid translocation of G protein-coupled receptor
      kinase (GRK) from the cytosol to the plasma membrane within 1 hr of exposure. In
      addition, purified preparations of the A1AR that were phosphorylated with
      purified recombinant GRK-2 demonstrated enhanced affinity for arrestin over
      Gi/Go. These results indicate rapid and functional desensitization of the A1AR by
      brief exposure to agonist. The mechanism underlying this event seems to involve
      phosphorylation of the A1AR, presumably by the GRK or GRKs.

PMID- 9281609
TI  - (-)-Epigallocatechin-3-gallate blocks the induction of nitric oxide synthase by
      down-regulating lipopolysaccharide-induced activity of transcription factor
      nuclear factor-kappaB.
AB  - Nitric oxide (NO) plays an important role in inflammation and multiple stages of
      carcinogenesis. We investigated the effect of various tea polyphenols and
      caffeine on the induction of NO synthase (NOS) in thioglycollate-elicited and
      lipopolysaccharide (LPS)-activated peritoneal macrophages. Gallic acid (GA), (-)
      epigallocatechin (EGC), and (-)-epigallocatechin-3-gallate (EGCG), the major tea
      catechin, were found to inhibit inducible NOS (iNOS) protein in activated
      macrophages. EGCG, a potent antitumor agent with anti-inflammatory and
      antioxidant properties, inhibited NO generation, as measured by the amount of
      nitrite released into the culture medium. Inhibition of NO production was
      observed when cells were cotreated with EGCG and LPS. iNOS activity in soluble
      extracts of lipopolysaccharide-activated macrophages treated with EGCG (5 and 10
      microM) for 6-24 hr was significantly lower than that in macrophages without EGCG
      treatment. Western blot, reverse transcription-polymerase chain reaction, and
      Northern blot analyses demonstrated that significantly reduced 130-kDa protein
      and 4.5-kb mRNA levels of iNOS were expressed in lipopolysaccharide-activated
      macrophages with EGCG compared with those without EGCG. Electrophoretic mobility
      shift assay indicated that EGCG blocked the activation of nuclear factor-kappaB,
      a transcription factor necessary for iNOS induction. EGCG also blocked
      disappearance of inhibitor kappaB from cytosolic fraction. These results suggest
      that EGCG decreases the activity and protein levels of iNOS by reducing the
      expression of iNOS mRNA and the reduction could occur through prevention of the
      binding of nuclear factor-kappaB to the iNOS promoter, thereby inhibiting the
      induction of iNOS transcription.

PMID- 9281610
TI  - Nucleotide regulation and characteristics of potassium channel opener binding to
      skeletal muscle membranes.
AB  - [3H]P1075 binding to membrane preparations of rabbit skeletal muscle were
      observed in the presence of nucleotide triphosphates or diphosphates but not AMP,
      cAMP, adenosine, tripolyphosphate, or pyrophosphate. Nonhydrolyzable or poorly
      hydrolyzable ATP analogs inhibited MgATP-supported binding. The EC50 value for
      MgATP-supported binding (0.4 mM) was decreased approximately 10-fold in the
      presence of an ATP-regenerating system, and significant metabolism by membrane
      nucleotidases was confirmed by high performance liquid chromatographic analysis.
      [3H]P1075 bound to skeletal muscle with a Kd value of 37 +/- 3 nM and a Bmax
      value of 280 +/- 14 fmol/mg of protein. [3H]P1075 binding to subcellular
      fractions was highest in membranes enriched in T tubules. Specific binding was
      reversible, trypsin-sensitive, maximal at pH 8, and stereoselective for the
      (3S,4R)-enantiomer of cromakalim. Potassium channel openers exhibited a rank
      order of potency of P1075 > pinacidil > levcromakalim = BMS-180448 > nicorandil >
      diazoxide = BRL 38226. Fluorescein analogs (ethyleosin, phloxine B, and rose
      bengal) were relatively potent inhibitors of binding (Ki = 200-300 nM). The
      potassium channel openers cromakalim and BMS-180448 were competitive inhibitors
      of [3H]P1075 binding. In contrast, rose bengal and the ATP-regulated potassium
      channel antagonist glyburide increased the rate of [3H]P1075 dissociation in a
      manner consistent with noncompetitive interaction.

PMID- 9281611
TI  - Methylene blue is a muscarinic antagonist in cardiac myocytes.
AB  - We studied the mechanism of action of methylene blue (Mblue), a putative guanylyl
      cyclase inhibitor, on the L-type calcium current (ICa) and the muscarinic
      activated K+ current (IK,ACh) in rat ventricular and atrial myocytes,
      respectively, and on the binding of [3H]quinuclidinyl benzylate in rat
      ventricular membranes. Superfusion, but not internal dialysis, with 30 microM
      Mblue antagonized the inhibitory effect of acetylcholine (ACh, 1 microM) on beta
      adrenergic stimulation of ICa with isoprenaline (Iso, 10 nM or 1 microM).
      However, Mblue had no effect on the basal ICa or on the stimulation of ICa by Iso
      in the absence of ACh. The activation of IK,ACh by 3 microM ACh was also
      antagonized by Mblue in a dose-dependent manner. In contrast, Mblue had no effect
      on the activation of IK,ACh by either guanosine-5'-O-(3-thio)triphosphate or
      guanosine-5'-(beta,gamma-imido)triphosphate. Chlorpromazine (CPZ), a piperazine
      derivative like Mblue, also inhibited the muscarinic activation of IK,ACh in a
      dose-dependent manner. The specific binding of [3H]QNB, a muscarinic ligand, to
      rat ventricular membranes was displaced in a dose-dependent manner by Mblue and
      CPZ. The piperazine derivatives behaved like competitive antagonists of [3H]QNB
      binding, exhibiting equilibrium dissociation constant (Ki) values of 187 nM for
      Mblue and 366 nM for CPZ. In conclusion, Mblue exerts antimuscarinic effects on
      ICa and IK,ACh in rat cardiac myocytes that are best explained by the binding of
      Mblue to the M2 subtype of muscarinic receptors. This property probably
      contributes to the antimuscarinic effect of the putative guanylyl cyclase
      inhibitor reported in previous studies.

PMID- 9281612
TI  - Persistent activation by and receptor reserve for an irreversible A1-adenosine
      receptor agonist in DDT1 MF-2 cells and in guinea pig heart.
AB  - The p- and m-isothiocyanate adenosine derivatives N6-[4-[[[4-[[[[2-[[[(p-(m)
      isothiocyanatophenyl)amino]thiocarbonyl ]am
      ino]ethyl]amino]carbonyl]methyl]anilino]carbonyl]methyl]phenyl] adenosine (p- and
      m-DITC-ADAC) were examined for irreversible agonist effects at the A1-adenosine
      receptor (A1-AdoR) in DDT1 MF-2 (DDT) cells and a functional A1-AdoR response in
      the guinea pig isolated heart. The p- and m-DITC-ADAC inhibited (-)-isoproterenol
      stimulated cAMP accumulation in DDT cells in the low nanomolar range, and the
      maximal responses elicited by both compounds were similar to that for N6
      cyclopentyladenosine. Once established, the p-DITC-ADAC-mediated inhibition of
      cAMP accumulation in DDT cells was not affected by the addition of the AdoR
      antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX). Pretreatment of DDT cells
      with p-DITC-ADAC (1 microM), followed by washing, reduced [3H]CPX binding to the
      A1-AdoR by 44% without altering the Kd value for the radioligand to the remaining
      receptors. The relationship between irreversible A1-AdoR occupancy by p-DITC-ADAC
      and inhibition of cAMP accumulation revealed a relatively large receptor reserve
      (64%) for the maximal response. In guinea pig isolated hearts, m-DITC-ADAC (5
      microM) prolonged the stimulus to His bundle (SH) interval by 2.1-fold; this
      response could be prevented by the antagonist 8-cyclopentyltheophylline (5
      microM). However, after the SH interval prolongation was established, extensive
      washout or the addition of 8-cyclopentyltheophylline had little reversal effect
      on the m-DITC-ADAC response. Binding of [3H]CPX to the guinea pig ventricular
      membranes after m-DITC-ADAC treatment and washing was reduced by 35%. The A1-AdoR
      occupancy response relationship for m-DITC-ADAC to prolong the SH interval
      indicated a small (10-20%) receptor reserve. Both p -and m-DITC-ADAC seem to be
      irreversible full agonists at the A1-AdoR and may prove to be useful probes to
      further investigate A1-AdoR structure-function relationships.

PMID- 9281613
TI  - A mutational analysis of residues essential for ligand recognition at the human
      P2Y1 receptor.
AB  - We conducted a mutational analysis of residues potentially involved in the
      adenine nucleotide binding pocket of the human P2Y1 receptor. Mutated receptors
      were expressed in COS-7 cells with an epitope tag that permitted confirmation of
      expression in the plasma membrane, and agonist-promoted inositol phosphate
      accumulation was assessed as a measure of receptor activity. Residues in
      transmembrane helical domains (TMs) 3, 5, 6, and 7 predicted by molecular
      modeling to be involved in ligand recognition were replaced with alanine and, in
      some cases, by other amino acids. The potent P2Y1 receptor agonist 2-methylthio
      ATP (2-MeSATP) had no activity in cells expressing the R128A, R310A, and S314A
      mutant receptors, and a markedly reduced potency of 2-MeSATP was observed with
      the K280A and Q307A mutants. These results suggest that residues on the exofacial
      side of TM3 and TM7 are critical determinants of the ATP binding pocket. In
      contrast, there was no change in the potency or maximal effect of 2-MeSATP with
      the S317A mutant receptor. Alanine replacement of F131, H132, Y136, F226, or H277
      resulted in mutant receptors that exhibited a 7-18-fold reduction in potency
      compared with that observed with the wild-type receptor. These residues thus seem
      to subserve a less important modulatory role in ligand binding to the P2Y1
      receptor. Because changes in the potency of 2-methylthio-ADP and 2-(hexylthio)
      AMP paralleled the changes in potency of 2-MeSATP at these mutant receptors, the
      beta- and gamma-phosphates of the adenine nucleotides seem to be less important
      than the alpha-phosphate in ligand/P2Y1 receptor interactions. However, T221A and
      T222A mutant receptors exhibited much larger reductions in triphosphate (89- and
      33-fold versus wild-type receptors, respectively) than in diphosphate or
      monophosphate potency. This result may be indicative of a greater role of these
      TM5 residues in gamma-phosphate recognition. Taken together, the results suggest
      that the adenosine and alpha-phosphate moieties of ATP bind to critical residues
      in TM3 and TM7 on the exofacial side of the human P2Y1 receptor.

PMID- 9281614
TI  - Selective inhibition of adenylyl cyclase type V by the dopamine D3 receptor.
AB  - Despite a great deal of research, the second messenger coupling of the dopamine
      D3 receptor has not yet been clearly established. The closely related D2 and D4
      receptors have been shown to inhibit adenylyl cyclase activity in a variety of
      cell types, but the D3 receptor has little or no effect on this second messenger
      system. We now demonstrate that when the D3 receptor and adenylyl cyclase type V
      are coexpressed in 293 cells, the agonist quinpirole causes 70% inhibition of
      forskolin-stimulated cAMP levels. This effect seems to be selective for this
      adenylyl cyclase isoform because the D3 receptor does not inhibit adenylyl
      cyclase types I or VI and only weakly stimulates adenylyl cyclase type II. In
      contrast, the D2 receptor inhibits cAMP accumulation in 293 cells in the absence
      of cotransfected adenylyl cyclases and stimulates adenylyl cyclase type II to a
      greater extent than the D3 receptor. The inhibition of adenylyl cyclase type V by
      the D3 receptor is sensitive to pertussis toxin, suggesting the involvement of G
      proteins of the Gi family. Guanosine-5'-O-(3-thio)triphosphate binding studies
      indicate that the D3 receptor weakly activates all three Gialpha subunits,
      whereas the D2 receptor activates these G proteins to a substantially greater
      extent. However, despite its relative inability to promote G protein activation,
      the D3 receptor is capable of substantial and consistent inhibition of adenylyl
      cyclase type V. The robust second messenger coupling of the D3 receptor in a
      heterologous system with defined components provides a system for further studies
      of the function of this receptor and should facilitate the development and
      characterization of new D3 receptor ligands.

PMID- 9281615
TI  - Regulation of human alpha4beta2 neuronal nicotinic acetylcholine receptors by
      cholinergic channel ligands and second messenger pathways.
AB  - The alpha4beta2 nicotinic acetylcholine receptors (nAChRs), a major subtype in
      the brain, have been shown to be modulated by chronic treatment with nicotine. In
      this study, the regulation of recombinant human alpha4beta2 nAChR subtype by (-)
      nicotine and other cholinergic channel modulators was studied using human
      embryonic kidney 293 cells stably expressing this subunit combination. The
      treatment of transfected cells with (-)-nicotine and other activator ligands,
      including (-)-cytisine, 1,1-dimethyl-4-phenylpiperazinium, (S)-3-methyl-5-(1
      methyl-2-pyrrolidinyl)isoxazole, and (+/-)-epibatidine, resulted in concentration
      dependent increases in the levels of alpha4beta2 nAChRs. The increase in
      [3H]cytisine binding sites was initiated by low concentrations of (-)-nicotine
      (<100 nM); was maximal at 10 microM (15-fold), rapid (t0.5 = 4.0 +/- 0.5 hr), and
      totally reversible (t0.5 = 11.7 +/- 0.1 hr); and occurred with no change in
      ligand binding affinity. Antagonists, including dihydro-beta-erythroidine, d
      tubocurarine, and methyllycaconitine, also elicited significant increases in
      receptor levels. A good correlation was observed between the Ki values for
      binding inhibition and the EC50 values for receptor up-regulation. Treatment of
      cells with mecamylamine, a noncompetitive antagonist, did not change receptor
      levels or alter (-)-nicotine-evoked up-regulation. (-)-Nicotine-evoked up
      regulation was blocked by cycloheximide, suggesting a role for protein synthesis.
      Treatment of cells with (-)-nicotine or dihydro-beta-erythroidine differentially
      modulated the efficacy of acetylcholine to activate cation efflux. Both 6-beta
      [beta'(piperidino)propionyl]forskolin and phorbol-12-myristate-13-acetate
      increased [3H]cytisine binding sites and nAChR function and enhanced the effects
      of chronic (-)-nicotine treatment in a synergistic manner. These results
      collectively demonstrate that human alpha4beta2 nAChRs can be differentially up
      regulated by chronic treatment with nAChR ligands and activation of protein
      kinase A- and protein kinase C-dependent mechanisms.

PMID- 9281616
TI  - The role of Src kinase in the potentiation by ethanol of cytokine- and endotoxin
      mediated nitric oxide synthase expression in rat hepatocytes.
AB  - This study demonstrates that exposure of primary rat hepatocytes or mouse BNL
      Cl.2 liver cell line to ethanol causes potentiation of tumor necrosis factor
      alpha (TNF-alpha)- and lipopolysaccharide (LPS)-stimulated nitrite accumulation.
      The potentiating effect of ethanol (0.02-2 mM) appears to be time and
      concentration dependent. Consistent with nitrite production, the amount of
      inducible nitric oxide synthase (iNOS) mRNA and protein is initially detected at
      4 hr after treatment with TNF-alpha/LPS/ethanol. Furthermore, the capability of
      these agents to induce iNOS expression is primarily determined by the age of the
      animals. Interestingly, antioxidants such as N-acetylcysteine (NAC), ascorbic
      acid, or alpha-tocopherol fail to inhibit TNF-alpha/LPS/ethanol-induced increase
      in iNOS protein. In addition, several kinase inhibitors, including staurosporine,
      genistein, curcumin, and herbimycin A, were used to examine their effects on this
      induction. Among them, only herbimycin A potently inhibits the accumulation of
      nitrite and iNOS expression. In vitro kinase assay verifies that Src tyrosine
      kinase is rapidly activated with a peak at 1 hr after treatment with TNF
      alpha/LPS/ethanol but is not activated by these agents singly or doubly. As
      expected, herbimycin A can block Src kinase activity under circumstances in which
      iNOS expression is also inhibited. However, our results do not indicate that the
      mitogen-activated protein kinase is activated after treatment with these agents.
      The study results suggest that Src tyrosine kinase plays a prominent role in
      transducing the signal to induce iNOS expression in hepatocytes treated with TNF
      alpha/LPS/ethanol.

PMID- 9281617
TI  - Beneficial effects of a novel thyromimetic on lipoprotein metabolism.
AB  - Although L-triiodothyronine (L-T3) lowers cholesterol, this hormone is not used
      to treat hypercholesterolemia because of its cardiotoxic effects. Thyromimetics,
      such as the novel compound CGS 23425, that mimic the beneficial but lack the
      detrimental effects of T3, may be useful in the treatment of
      hypercholesterolemia. To show that CGS 23425 has no cardiotoxicity, atrial
      contractility and force were both measured and found to be unchanged in rats
      treated with up to 10 mg/kg drug. The lipid lowering actions of this drug
      resulted in a 44% decrease in low-density lipoprotein (LDL) cholesterol in
      hypercholesterolemic rats treated with 10 microg/kg of the compound. Normal rats
      required a higher dose of 1000 microg/kg to elicit a similar 50% reduction in LDL
      cholesterol. Both CGS 23425 or T3 (10 nM) increased the specific binding of 125I
      labeled LDL to Hep G2 cells and increased LDL receptor number by 44 and 49%,
      respectively. These data indicate that CGS 23425 enhances hepatic clearance of
      serum LDL cholesterol. Normal and fat-fed animals treated with the drug showed a
      dose-dependent increase in apolipoprotein AI, a protein that promotes the efflux
      of cholesterol from peripheral tissues. Transient transfection of a rat
      apolipoprotein AI promoter-chloramphenicol acetyltransferase construct, in human
      hepatoma cells, showed a dose-dependent increase in chloramphenicol
      acetyltransferase activity with EC50 values of 2 x 10(-12) M and 10(-10) M for
      thyroid hormone receptors beta1 and alpha1, respectively, with maximal responses
      at 10(-7) M. These data indicate that CGS 23425 is a thyromimetic that increases
      apolipoprotein AI expression via thyroid hormone receptor. In summary, CGS 23425
      ameliorates hypercholesterolemia by increasing apolipoprotein A1 and the
      clearance of LDL cholesterol. Therefore, a compound like CGS 23425 may be useful
      for the prevention and reversal of atherosclerosis.

PMID- 9281812
TI  - Does ovarian granulosa and theca cell interaction in co-culture affect the
      cytoplasmic microtubule organization?
AB  - Theca (T) cells modulate steroid secretion by granulosa (G) cells in vitro. This
      investigation was undertaken to see whether the cytoskeleton is involved in this
      process. Monocultures of G cells alone, T cells alone and GT co-cultures were
      viewed by light microscopy. Microtubules were visualized using monoclonal Ab
      against tubulin. The specificity of the Ab was checked by Western blotting. One
      group of cells was treated with colchicine, a microtubule disrupting drug, to
      show its influence on oestradiol secretion by cultured cells. Microtubule
      arrangement was monitored using a fluorescence microscope. In monoculture of G
      cells a diffuse pattern of immunocytochemical staining of tubulin was noted while
      in T cells cultured alone the microtubule were arranged in a network of delicate
      fibres. In co-culture the microtubule arrangement changed in G cells and became
      very fine and less numerous than in theca fibres. Oestradiol secretion by
      colchicine-treated cultures different from control secretions. The E2 secretion
      declined in cultures of G cells (48.9 pg/10(5) cells in control vs 19.4 pg/10(5)
      cells in colchicine cells), and in T cells cultures alone (490 pg i n control vs
      171 pg/10(5) cells in colchicine treated cells) while in co-culture a dose
      dependent increase of this steroid was detected after the addition of colchicine
      (2,008 pg vs 1,269 pg/10(5) cells in control). It is conceivable that
      microtubules affect transport of androgens from their production site in T cells
      to G cells where this substrate is aromatized resulting in increased preovulatory
      oestradiol secretion.

PMID- 9281813
TI  - Comparison of slime production under aerobic and anaerobic conditions.
AB  - A total of sixteen clinical isolates of coagulates-negative staphylococci were
      investigated for slime production by the test tube and Congo red agar method. In
      order to determine the role of oxygen in slime production, Staphylococcus
      epidermidis culture plate assay was performed under aerobic and anaerobic
      conditions. Findings revealed that the slime production was less under the
      anaerobic conditions.

PMID- 9281814
TI  - Preliminary observations on the induction of triploidy in Abramis brama by cold
      shock.
AB  - Cold shock (2 degrees C) lasting for 45 or 60 min was applied to eggs from bream
      (Abramis brama), beginning at 2, 3, 4, 5, 6, 7 and 8 min after fertilization. The
      lowest survival rate was observed in those groups treated in which a cold shock
      started at 4 or 5 min after fertilization. Groups exposed to cold shock lasting
      for 60 min showed a higher percentage of triploids than in groups shocked for 45
      min. The highest yield of triploid embryos was produced by the cold shock which
      started 8 min after egg fertilization and which lasted for 45 min.

PMID- 9281815
TI  - Subcellular distribution of jacalin in Artocarpus integrifolia seed.
AB  - Seeds of Artocarpus integrifolia (jack fruit) contain large amounts of the anti-T
      lectin, jacalin. The mature seeds of jack fruit were homogenized in 0.25 M
      sucrose and separated by differential centrifugation into four fractions, viz
      wall, intermediate, and microsomal pellets and soluble supernatant. The lectin
      activity was associated with the wall pellet collected at low speed
      centrifugation. The other three fractions obtained by centrifugation at gradually
      higher speeds contained a similar lectin but of very low specific activity. The
      distribution pattern of jacalin remained unchanged in the presence of EDTA and/or
      Triton X-100 indicating that the lectin was not membrane bound. Immunofluorescent
      staining of jack fruit seeds showed that jacalin was localized in the cell wall
      in the intracellular space, which corroborated the results of fractionation
      studies. The possible relevance of these results to the function of lectin in the
      plant cell is discussed.

PMID- 9281816
TI  - Note: genetic and biochemical characterization on nisin Z produced by Lactococcus
      lactis ssp. lactis biovar. diacetylactis UL 719.
AB  - The bacteriocin produced by Lactococcus lactis ssp. lactis biovar. diacetylactis
      UL 719 was purified and characterized. Two peaks exhibiting antimicrobial
      activity were obtained after purification. Primary structure of the peptide of
      major peak 2 was identical to that of nisin Z when determined by Edman
      degradation and confirmed by DNA sequence analysis. The molecular mass as
      determined by mass spectrometry was 3346.39 +/- 0.40 Da for peak 1 and 3330.39 +/
      0.27 Da for peak 2, which suggests that peak 1 may correspond to an oxidized
      form of nisin Z. The two purified peaks exhibiting antimicrobial activity appear
      to correspond with oxidized and native forms of nisin Z.

PMID- 9281817
TI  - Proteolytic enzyme activity in lactococci grown in different pretreated milk
      media.
AB  - Lactococcus lactis ssp. lactis MG1363, harbouring plasmid pNZ521, which encodes
      the extracellular serine proteinase (PrtP) from strain SK110, was used to study
      the effect of two different treatments of the growth medium milk on the activity
      levels of PrtP and the intracellular localized aminopeptidase PepN and X-prolyl
      dipeptidyl aminopeptidase PepXP. All three proteolytic enzymes showed lower
      activity levels in cells grown in high heat-treated milk as compared to cells
      grown in non-heat-treated milk. Highest activity levels of the three studied
      enzymes were found in cells grown in milk heat treated for 30 min at 63 degrees
      C. Using cells of strain L. lactis ssp. lactis MG1363, harbouring plasmid pNZ544,
      which encodes reporter gene gusA under control of the prtP promoter, it was
      demonstrated that the regulation of PrtP takes place at the transcription
      initiation level. After separation of the pH 4.6 soluble fraction of high heat
      treated milk with reverse phase HPLC, it was found that the hydrophilic small
      peptide fraction of the milk was responsible for this regulation. Amino acid
      analysis of this fraction confirmed that this fraction consisted of peptides
      only. Ultrafiltration of milk, which increases the dry matter of the milk
      specifically through increase of its protein content, only significantly affected
      the levels of PrtP and PepN in cells of strain MG1363. Highest activity was found
      during growth in unconcentrated milk, and the lowest level was found during
      growth in four times concentrated retentate. Using cells of strain
      MG1363(pNZ544), it was demonstrated that also in this case regulation of PrtP
      takes place at the level of transcription initiation. Approximately 40% of the
      decrease in activity of PrtP and PepN could be explained by the presence of
      higher amounts of purified whey proteins and higher amounts of dry mass. This
      suggests the presence of another factor, concentrated by ultrafiltration, which
      controls the production different proteolytic enzymes in concentrated retentate.

PMID- 9281818
TI  - Metabolic fingerprinting and fermentative capacity of the intestinal flora of
      pigs during pre- and post-weaning periods.
AB  - We used the Phene Plate generalized microplates to investigate the metabolic
      activities of faecal flora of pigs during pre- and post-weaning periods. Weekly
      samples were collected from four sows and their litters (four piglets from each)
      during 5 months. The metabolic fingerprints obtained from faecal floras of sows
      and their litters in the first sampling occasion was very similar, suggesting
      that sows were the initial source of flora for piglets. This similarity, however,
      was lost in week 2 and piglets developed new types of flora which, although
      similar among the litter-mates, differed from those of the sows. The metabolic
      fingerprints of pigs' floras during the post-weaning period also differed from
      those of the suckling period. On day 70 pigs were transferred to a fattening
      stable. The faecal flora of the animals during this period was unstable in each
      individual and differed among litter-mates. A pattern of successive changes was
      observed in the fermentative capacity (FC) of pigs' floras reaching the highest
      value before weaning (day 34). An overall decrease in the FC value of faecal
      floras was observed as a consequence of dietary shifts from milk to solid food to
      high energy fattening diet. The mean FC value of pig floras on the first sampling
      occasion (mean +/- S.D. = 0.41 +/- 0.02) was significantly higher than that
      obtained in the last sampling occasion (day 145) (0.31 +/- 0.04) (P < 0.001).
      Faecal floras of sows also had lower FC values (0.25 +/- 0.01) than those of
      piglets suggesting that loss of FC by the faecal flora of young pigs will
      continue as they age.

PMID- 9281819
TI  - Plasmids and bacterial resistance to biocides.
AB  - Plasmid-encoded bacterial resistance to antibiotics and to anions and cation
      (including important mercurial and silver compounds) has been widely studied.
      Plasmid-mediated resistance to organic cationic agents which are important
      biocides has been described for chlorhexidine and quaternary ammonium compounds
      (and also for the less important acridine, diamidines and ethidium bromide) in
      antibiotic-resistant Staphylococcus aureus and Staph. epidermidis strains.
      Plasmids may also encode reduced biocide susceptibility of Gram-negative
      bacteria, but intrinsic resistance is likely to be of greater significance.
      Antibiotic resistance and biocide resistance may be linked but this is not always
      found clinically.

PMID- 9281821
TI  - Carbenicillin-hydrolysing penicillinase mediated by a plasmid of Proteus
      mirabilis and its relationship to the PSE-type enzymes of Pseudomonas aeruginosa.
AB  - The nucleotide sequence of a carbenicillin-hydrolysing (carbenicillinase) gene
      occurring in an endogenous plasmid, pCS229, of Proteus mirabilis was determined.
      The amino acid sequence of the mature enzyme, comprising 271 amino acids with a
      molecular mass of 29,506 Da, was deduced. The pCS229 carbenicillinase showed only
      46.4% similarity, in the overall amino acid sequence, to the chromosomal
      carbenicillinase of Pr. mirabilis GN79; however, the enzyme showed about 98%
      similarity to a Pseudomonas-specific plasmid-encoded carbenicillinase, PSE-4,
      that was isolated from Pseudomonas aeruginosa. Only five of 271 amino acids
      differed from those of PSE-4. This study proved the close relationship between
      the carbenicillinase genes distributed in Pr. mirabilis and Ps. aeruginosa.

PMID- 9281820
TI  - Formate and ethanol are the major products of glycerol fermentation produced by a
      Klebsiella planticola strain isolated from red deer.
AB  - The rumen contents of red deer (Cervus elaphus) were used to isolate bacterial
      capable of fermenting glycerol. The biochemistry, physiology, morphology and
      phylogeny of one isolate were studied in detail. The isolate (DR3) was
      tentatively identified as a strain of the species Klebsiella planticola as based
      on phenotypic characterization. The data obtained from 16S rRNA sequence analysis
      showed that the deer rumen isolate DR3 was 99.7% similar to the type strain of
      Kl. planticola (DSM 3069T), thus confirming the results of the phenotypic
      characterization. During cell growth, it was established that glycerol
      dissimilation by Kl. planticola DR3 led to the production of formate and ethanol
      at equimolar levels of 32 mmol 1(-1) and 30 mmol 1(-1), respectively. As a result
      of the data obtained, a closed carbon balance was constructed for Kl. planticola
      DR3. This finding represented the first report of the complete end-product
      profile for glycerol dissimilation by a strain of Kl. planticola isolated from
      cervine rumen contents.

PMID- 9281822
TI  - The effect of high hydrostatic pressure on Listeria monocytogenes in phosphate
      buffered saline and model food systems.
AB  - Three strains of Listeria monocytogenes (NCTC 1194, a poultry isolate and the
      Scott A strain) were exposed to a range of pressures (300, 350, 375, 400 and 450
      MPa) in 10 mmol 1(-1) phosphate-buffered saline (PBS) at pH 7.0 for up to 30 min
      at ambient temperature. Generally, increasing the magnitude and duration of
      compression resulted in increasing levels of inactivation, although the
      inactivation kinetics varied depending on the strain and pressure applied. The
      three strains also exhibited a wide variation in their resistance to high
      pressure. The resistance of the three strains to high pressure (375 MPa) was also
      assessed in a series of model food systems containing one of each of the three
      main food constituents: protein (1, 2, 5 and 8% w/v bovine serum albumin in PBS),
      carbohydrate (1, 2, 5 and 10% w/v glucose in PBS) and lipid (olive oil (30% v/v)
      in PBS emulsion). Overall, increasing the concentrations of bovine serum albumin
      (BSA) and glucose in the suspending medium resulted in decreasing levels of
      inactivation of all three strains; however, the minimum concentration of BSA and
      glucose required to increase survival to a level greater than that observed in
      PBS alone varied depending on the strain and on the duration of the treatment.
      The survival of all three strains was greater in the olive oil/PBS emulsion than
      in PBS alone at all treatment times.

PMID- 9281823
TI  - A study of the microflora of some recycled fibre pulps, boards and kitchen rolls.
AB  - Current methodology used for studying the microflora of pulps and boards was
      assessed and some improvements are recommended. Microbiological quality of 37
      samples including recycled fibre pulps, boards, kitchen rolls, virgin fibre
      sheets and circulating process water were investigated. The papermaking process
      had drastically reduced the total microbial counts. The dominant microflora in
      all the samples were aerobic bacteria. The amounts in boards were only 10(3)
      10(6) cfu g-1 d.w., whereas the untreated pulps contained 10(8)-10(10) cfu g-1
      d.w. Aerobic, anaerobic and facultatively anaerobic spore-forming bacteria formed
      a large group in the bacterial flora of pulp samples (10(3)-10(6) and 10(2)-10(4)
      cfu g-1 d.w., respectively). In the boards the maximum numbers of aerobic spore
      forming bacteria were about 10(4) cfu g-1 d.w. and the numbers of anaerobic and
      facultatively anaerobic spore formers were negligible. Moulds were common in the
      untreated pulp sampled at 10(2)-10(6) cfu g-1 d.w., but their occurrence in
      boards was close to the detection limit. Yeasts were common only in the pulps of
      one mill, and were found to be present in the circulation process water. Both
      mesophilic and thermophilic actinomycetes were detected in pulps at levels up to
      10(2)-10(5) cfu g-1 d.w. However, no mesophilic actinomycetes were detected in
      boards, although some boards contained up to 10(2) cfu g-1 d.w. of thermophilic
      actinomycetes. The virgin fibre sheets were practically free of microbes. Only a
      few bacterial colonies were detected from the kitchen rolls.

PMID- 9281824
TI  - Rapid quantitative analysis of binary mixtures of Escherichia coli strains using
      pyrolysis mass spectrometry with multivariate calibration and artificial neural
      networks.
AB  - Pyrolysis mass spectrometry (PyMS) and multivariate calibration were used to show
      the high degree of relatedness between Escherichia coli HB101 and E. coli UB5201.
      Next, binary mixtures of these two phenotypically closely related E. coli strains
      were prepared and subjected to PyMS. Fully interconnected feedforward artificial
      neural networks (ANNs) were used to analyse the pyrolysis mass spectra to obtain
      quantitative information representative of level of E. coli UB5201 in E. coli
      HB101. The ANNs exploited were trained using the standard back propagation
      algorithm, and the nodes used sigmoidal squashing functions. Accurate
      quantitative information was obtained for mixtures with > 3% E. coli UB5201 in E.
      coli HB101. To remove noise from the pyrolysis mass spectra and so lower the
      limit of detection, the spectra were reduced using principal components analysis
      (PCA) and the first 13 principal components used to train ANNs. These PCA-ANNs
      allowed accurate estimates at levels as low as 1% E. coli UB5201 in E. coli HB101
      to be predicted. In terms of bacterial numbers, it was shown that the limit of
      detection of PyMS in conjunction with ANNs was 3 x 10(4) E. coli UB5201 cells in
      1.6 x 10(7) E. coli HB101 cells. It may be concluded that PyMS with ANNs provides
      a powerful and rapid method for the quantification of mixtures of closely related
      bacterial strains.

PMID- 9281825
TI  - Identification of sites of injury in Lactobacillus bulgaricus during heat stress.
AB  - Heat resistance of Lactobacillus bulgaricus in skimmed milk at 62 degrees, 64
      degrees, 65 degrees and 66 degrees C was studied. The response to increasing
      temperatures in this range was not linear, with temperatures at 65 degrees C and
      above giving a lower survival rate than would be predicted from experiments at
      lower temperatures. To identify sites of injury at these temperatures, chemical
      markers were used. Heating at 64 degrees C and below resulted in damage to the
      cytoplasmic membrane. At temperatures of 65 degrees C and above chemical markers
      also indicated damage in the cell wall and proteins. Using differential scanning
      calorimetry analysis of whole cells of Lact. bulgaricus seven main peaks were
      observed (1-51, m1-61, m2-73, n-80, p-89, q-100, r-112 degrees C). Three of these
      peaks (l(r), m(r) and p(r)) were the result of reversible reactions. Analysis of
      cell fractions identified the cell structure involved in giving rise to each of
      the three reversible peaks; l(r), cell membrane lipids, m(r), ribosomes, and
      p(r), DNA. The evidence presented in this paper shows that irreversible reactions
      in the cell ribosomes are a critical site of damage in Lact. bulgaricus during
      heat stress in liquid media at 65 degrees C and above.

PMID- 9281826
TI  - Diversity and partial characterization of putative virulence determinants in
      Pasteuria penetrans, the hyperparasitic bacterium of root-knot nematodes
      (Meloidogyne spp.).
AB  - Antigens recognized by monoclonal antibodies (Mabs) raised to the surface of the
      obligate nematode hyperparasite Pasteuria penetrans were characterized. Using the
      attachment of spores of the bacterium to host nematodes to determine the
      biological variability present on the spore surface greatly underestimated the
      amount of surface heterogeneity present compared with estimates from
      immunological techniques. This heterogeneity differed not only between different
      individual spores from the same population but also between different spore
      populations. None of the Mabs completely inhibited any spore population from
      attaching to the nematode cuticle, suggesting that the mechanism of attachment
      may be more complex than previously supposed. Chemical degradation of one
      particular epitope recognized by monoclonal antibody PP1/117, and designated
      ep117, occurred after treatment with NaOH, periodate or Proteinase K, suggesting
      that an O-linked glycoprotein may be involved. Fibronectin, which had been found
      to bind to Pasteuria spores through hydrophobic interactions, also prohibited the
      Mab from recognizing ep117. However, SDS-PAGE of spore extracts followed by
      immunoblotting showed that none of the Mabs could detect this epitope and so
      ep117 may be conformational in nature. Thus, the conformation of any particular
      epitope recognized by a Mab may be important in determining to which nematode a
      particular spore will attach. The distribution of a particular epitope within a
      population of spores will in turn therefore determine its virulence on a
      particular nematode.

PMID- 9281827
TI  - In vitro 14C-amino acid fermentation by CF3, a characterized continuous-flow
      competitive exclusion culture of caecal bacteria.
AB  - Competition for growth-limiting nutrients by broiler caecal bacteria and
      Salmonella has been suggested as one factor associated with decreased Salmonella
      caecal colonization. The amino acids arginine, aspartic acid, serine and
      threonine have been indicated as Salmonella growth-limiting nutrients. Broiler
      caecal bacteria maintained in a continuous-flow culture (CF3) were used as
      inoculum for media containing 14C-arginine, 14C-aspartic acid, 14C-serine or 14C
      threonine. The 14C-labelled amino acids, except 14C-arginine, were metabolized to
      lactic, formic, acetic, propionic and butyric acids. In glucose-based media, 72%,
      72% and 33% of the radiolabel from aspartic acid, serine and threonine,
      respectively, were detected in organic acids. Fermentation without glucose
      resulted in 48%, 50% and 71% of the radiolabel from aspartic acid, serine and
      threonine, respectively, being detected in organic acids. Results indicated that
      the early establishment of CF3 in young chicks may result in the depletion of
      growth-limiting amino acids and, therefore, reduction of Salmonella colonization.

PMID- 9281828
TI  - A non-intrusive method for the measurement of water vapour sorption by bacterial
      spores.
AB  - Single particle levitation (SPL) is used to measure the sorption and desorption
      of water vapour from microparticles comprising of Bacillus spores. Water gain is
      determined from increases in the weight-balancing levitation voltages. Spore
      water isotherms are compared to values previously reported using bulk gravimetric
      methods. Two salient differences are found between the SPL and bulk data: (1)
      greater osmotic swelling is observed in the SPL data; and (2) the SPL data
      exhibit open loop hysteresis while bulk data exhibit closed loop hysteresis.

PMID- 9281829
TI  - Detection of bacteriocins of lactic acid bacteria isolated from foods and
      comparison with pediocin and nisin.
AB  - A total of 663,533 colonies from 72 dairy and meat sources showed a detection
      rate of 0.2% for bacteriocin producers using direct plating techniques. A further
      83,000 colonies from 40 fish and vegetable sources showed a detection rate of
      3.4% for bacteriocin producers using selective enrichment procedures. A
      collection of seven purified isolates showing a different host spectrum of
      bacteriocin activity and with the ability to produce bacteriocins in broth
      culture were compared with nisin and pediocin (with respect to their inhibitory
      activity, determined by the critical dilution method), against various indicator
      bacteria in agar and broth. The sensitivity of Listeria species to various
      bacteriocins was influenced by the agar and broth test systems used. A
      Lactobacillus curvatus strain was found to be the most suitable indicator for
      quantitating antimicrobial effects of all the bacteriocins investigated in both
      agar and broth test systems. The bacteriocin-producing isolates were
      characterized by biochemical reactions and DNA restriction enzyme profiles and
      taxonomic identification revealed species of Lactobacillus, Carnobacterium and
      Lactococcus assigned on the basis of 16S rDNA sequences.

PMID- 9281830
TI  - The use of bacteriophage-based systems for the separation and concentration of
      Salmonella.
AB  - Techniques for the separation/concentration of micro-organisms from background
      food matrices can be applied to increase the speed of analysis and ease of
      isolation and detection of target micro-organisms. One recent example of such a
      technique is the immunomagnetic separation (IMS) procedure that has been used for
      the separation of specific micro-organisms from foods. This paper describes the
      use of a novel biosorbent consisting of a Salmonella-specific bacteriophage
      (phage) immobilized to a solid phase that was used for the separation and
      concentration of Salmonella from food materials. This work has shown that a
      Salmonella-specific phage-based biosorbent could remove Salmonella from culture
      fluid and separate Salmonella from suspensions of other Enterobacteriaceae. The
      ease of production of phage, high affinity of phage-cell interaction and the
      ability of phage to infect host cells in heterogeneous environments indicates the
      potential of such a biosorbent as the basis for a reliable separation system in
      food microbiological analysis.

PMID- 9281831
TI  - The role of working memory capacity in retrieval.
AB  - The verbal fluency task requires generation of category exemplars and appears to
      be an example of what M. Moscovitch (1995) calls a strategic test of memory
      retrieval. Four experiments explored the role of individual differences in
      working memory (WM) capacity on verbal fluency under various secondary load
      conditions. High WM participants consistently recalled more exemplars. However,
      load conditions caused a decline in recall only for high WM participants. Low WM
      participants showed no effect of secondary workload on exemplar generation. WM
      group differences and load effects were observed even in the 1st min of
      retrieval, which suggests that differences were not due to differences in
      knowledge. A model of retrieval is supported that relies on cue-based-automatic
      activation, monitoring of output for errors, controlled suppression of previously
      recalled items, and controlled strategic search.

PMID- 9281832
TI  - Effects of varying levels of expertise on the basic level of categorization.
AB  - Six experiments were conducted on the effects of expertise on basic-level
      categorization. Individuals with varying levels of knowledge about songbirds
      generated lists of attributes, named objects, identified and discriminated among
      object silhouettes, verified category membership at 4 hierarchical levels, and
      visually identified songbirds primed either by species-specific, related, or
      unrelated birdsong. Results indicated that the original basic level never lost
      its privileged status. Expertise increased access to categorical information at
      the subordinate level for intermediate exports and at both the subordinate and
      sub-subordinate levels for advanced experts, causing these sublevels to function
      as basic. Throughout the continuum of expertise, conceptual knowledge interacted
      with perception. Accordingly, experts attended to different and more subtle
      perceptual features than novices.

PMID- 9281835
TI  - Chemistry and biosynthesis of clavulanic acid and other clavams.

PMID- 9281836
TI  - Biosynthesis of fatty acids and related metabolites.

PMID- 9281837
TI  - The biosynthesis of plant alkaloids and nitrogenous microbial metabolites.

PMID- 9281838
TI  - Steroids: reactions and partial synthesis.

PMID- 9281839
TI  - beta-Phenylethylamines and the isoquinoline alkaloids.

PMID- 9281840
TI  - The impact of chronic radioactive stress on the immuno-physiological condition of
      small mammals.
AB  - The mass of internal organs and cellularity index of thymus and spleen were
      measured in small mammals inhabiting territories with a low level of chronic
      irradiation caused by the Chernobyl accident. Comparing with uncontaminated
      territories from the same region, bank voles (Clethrionomys glareolus)
      demonstrated an increase in liver and thymus mass and cellularity index of
      thymus, while sub-adult shrews (Sorex araneus) at contaminated territories had
      larger body mass, heavier spleen, kidney, and liver. These changes reflect an
      increase of tension in physiological and immunological processes in the small
      mammal populations in response to chronic irradiation, which have a non-specific,
      stress-causing nature. Laboratory mice, exposed to a single dose of irradiation
      equal to the annual dose received by wild animals at contaminated territories
      (0.07 Gy), in contrast, showed decreased mass of kidney, spleen and thymus, and
      cellularity of thymus and spleen compared to the control group. This shows a
      direct and specific impact of a single dose of irradiation.

PMID- 9281841
TI  - Intake of 226Ra, 210Pb and 210Po with food in Poland.
AB  - Intake with food and water of 226Ra, 210Pb and 210Po was determined for an adult
      population in regions of central, northern and northeastern Poland. The content
      of radionuclides was determined in the daily diet and, in the central region,
      also in foodstuffs and drinking water. The annual intake with foodstuffs was
      estimated on the basis of their average annual consumption. The 226Ra intake in
      northeastern Poland was approximately 17% higher than the overall average,
      correlating well with the higher concentration of this radionuclide in the soil.
      The 210Po/210Pb ratio was close to unity in the continental regions, whereas at
      the Baltic Sea coast it was approximately 1.5. The latter value can be ascribed
      to a larger consumption of fish for which the 210Po/210Pb ratio was found to be
      approximately 10. In central Poland the largest intake of 226Ra was with flour
      and vegetables (contribution approx. 60%), the largest intake of 210Pb was with
      flour and meat (approx. 50%) and the largest intake of 210Po was with fish
      (approx. 34%). From the intake and dose coefficient, annual effective doses were
      calculated. The dose from 210Pb and 210Po was approx. 54 mu Sv year-1, and the
      dose from 226Ra was approx. 4 mu Sv year-1.

PMID- 9281843
TI  - Sequential histology of the adult chimpanzee epididymis.
AB  - The chimpanzee epididymis consists of three gross anatomical regions: caput (Cp),
      corpus (Cr), and cauda (Cd). During epididymal transit, chimpanzee sperm undergo
      maturational changes (affecting motility, capacitation, and the acrosome
      reaction), which enable fertilization. Elucidation of the sequential histology of
      the chimpanzee epididymis is preliminary to determining the role of each region
      of epididymal duct in the process of sperm maturation. We report the histology,
      in the adult male chimpanzee, of sequential segments of epididymis from the
      proximal efferent ductules through the Cp, Cr, and Cd regions of the epididymis
      proper to the proximal ductus deferens. These data illustrate the gross
      architecture of the tissue and reveal the histology characteristic of the diverse
      epithelia composing the epididymal ducts at each level. The tubules composing the
      epididymis of the adult male chimpanzee present at least 16 histologically
      distinct epithelia and their transitional forms. Such diversity of epithelia
      suggests a corresponding diversity of function. Although there are some clear
      differences, the histological appearance of the ducts, and of the component
      epithelia of the chimpanzee epididymis, is remarkably similar to that reported
      for the human.

PMID- 9281842
TI  - Urinary excretion of ethylenethiourea in five volunteers on a controlled diet
      (multicentric study).
AB  - Urinary excretion of ethylenethiourea (ETU) was monitored for 8 days in a group
      of five male non-smoker volunteers on a diet, the items of which were assayed for
      ETU and carbon sulphide. Urinary excretion of ETU reflected the consumption of
      wine, fruit and vegetables. Urinary ETU concentrations ranged from 0.6 to 6.7
      micrograms/g creatinine. ETU concentrations in the food eaten by the volunteers
      were generally below the detection limit whereas in wine 8.8 micrograms/l ETU was
      detected. Evolution of carbon sulphide by food samples ranged from 0.03 to 0.17
      mg/kg. Mean (+/- S.D.) daily intake of ETU in wine was 3.5 +/- 0.2% of the
      acceptable daily intake (ADI): 0.070 +/- 0.004 micrograms/kg body wt. During the
      8 days of the study, an average of 48.3% of the ETU ingested in wine was excreted
      unmodified by the kidneys. Twenty-four hour urinary excretion of ETU was
      significantly correlated with daily intake of ETU (r = 0.768) and CS2 evolved by
      the daily food items (r = 0.414).

PMID- 9281844
TI  - Apoptosis is coordinately regulated with osteoblast formation during bone
      healing.
AB  - The ultimate fate of the expanded pool of osteoblasts formed following a typical
      bone injury is unclear. Since necrosis has not been described in the latter
      stages of bone healing, there must be some other mechanism by which obsolete
      osteoblasts are cleared from an injury site. We therefore evaluated the
      possibility that their removal is pre-programmed, by investigating the occurrence
      of apoptosis in rats that received a standardized bone injury. Histological
      evidence identical to that found in tissues known to exhibit apoptosis was
      obtained, thereby showing that programmed cell death was a normal concomitant of
      fracture healing. The concentration of apoptotic bodies reached its maximum after
      the differentiative response had peaked, suggesting that the two processes were
      coordinated. The same result was found in a second group of rats that received
      the same bone injury plus a simultaneous standardized soft-tissue injury. The
      combined injuries resulted in more osteoblasts and more apoptotic bodies, but an
      identical temporal relationship between the peak responses in the two parameters.
      The results suggested that osteoblasts were removed from the injury site via
      apoptosis, and that the process was coordinately regulated with differentiation.
      Since the number of apoptotic bodies per osteoblast varied during healing, it is
      likely that apoptosis was associated with healing and not merely with osteoblast
      concentration.

PMID- 9281845
TI  - Exosporial membrane plasticity of Clostridium sporogenes and Clostridium
      difficile.
AB  - This investigation examines the morphological alterations of the exosporial
      membranes of Clostridium sporogenes ATCC 3584 and Clostridium difficile ATCC
      43594 and 9689 endospores in relation to their possible function during
      germination in the attachment/colonization process of these pathogenic bacteria.
      There is no reported function for the exosporial membrane, nor exosporial
      appendages, of clostridial endospores. Advances in high resolution, scanning
      electron microscopy (SEM) permit the examination of these delicate, morphological
      projections on intact spores in the process of attachment. The morphological
      plasticity of the exosporial membrane projections during activation and
      germination was examined to determine whether the appearance of these exosporial
      projections coincided with attachment of the spores to the nutritive substrate,
      and whether this attachment could be altered by physical agitation, cation
      competition with Ba2+, chelation with EDTA, or treatment with colchicine.
      Following incubation, activated spores could not be removed from the agar surface
      by agitation in water (pH 7.2 or 9.1), nor by agitation in buffer or colchicine,
      indicating that some form of adherence or attachment to the agar had taken place.
      When agitated in the presence of Ba2+ or EDTA in phosphate buffered saline or
      EDTA in water, all activated spores detached from the agar and exhibited
      decreased exosporial projections and minimal, if any, attachment structures to
      the agar surface. Activated clostridial spores were found to attach to agar by
      delicate extensions of the exosporium that could be disrupted by EDTA or Ba2+
      exposure, but were unchanged when shaken in buffer or water.

PMID- 9281847
TI  - Separation of germ cell apoptosis from toxin-induced cell death by necrosis using
      in situ end-labeling histochemistry after glutaraldehyde fixation.
AB  - In situ end-labeling of fragmented DNA is routinely being used to detect
      apoptotic cells in various tissues including the testis. In this study, we
      examined the influence of various fixatives (neutral buffered formalin,
      paraformaldehyde, and glutaraldehyde) on the testicular structural integrity and
      immunoreactivity of fragmented DNA in apoptotic germ cells of the adult rat.
      Accelerated apoptosis of germ cells was induced in the adult rate by gonadotropin
      deprivation. Visualization of apoptotic DNA fragmentation in individual germ
      cells was achieved by direct immunoperoxidase detection of digoxigenin-labeled
      genomic DNA. Glutaraldehyde fixation significantly improved the in situ detection
      of apoptotic germ cells while maintaining excellent morphological preservation.
      The labeling is also specific for apoptosis since necrotic germ cells show no
      specific signals. Fixed tissues could be processed for electron microscopy for
      further characterization of germ cell death using morphological criteria. Thus,
      glutaraldehyde fixation is advantageous for recognition of apoptotic germ cells
      with high sensitivity and specificity on a cell-by-cell basis. It should also be
      applicable to detect apoptosis in other cells and tissues.

PMID- 9281846
TI  - Further observations on carbendazim-induced abnormalities of spermatid morphology
      in rats.
AB  - The effects of a microtubule poison, carbendazim, on rat spermiogenesis were
      examined for abnormalities of nuclei, acrosome and manchette in round and
      elongating spermatids in Stages VII-XII on days 7.5, 9.5, 10.0 and 10.5 post
      treatment using routine electron microscopy. Spermatid nuclear abnormalities were
      observed in Stages IX-XI on day 9.5 and at greater post-treatment intervals.
      Nuclear abnormalities included nuclear distortions, various types of nuclear
      invaginations and abnormal positioning of the modified nuclear envelope.
      Acrosomal abnormalities were noted on day 7.5 and at greater intervals.
      Discontinuous, multiple granular and fragmentary acrosomes were observed in
      Stages VII-XI. In addition, spermatids with complete absence of acrosome
      (acrosome-deficient spermatids) were observed in Stages VII-X. Poorly-formed and
      absent ectoplasmic specializations were seen in the cytoplasm of Sertoli cells
      next to the acrosome-deficient spermatids. A major abnormality of the manchette
      was irregular positioning of the manchette microtubules in steps 9-11 spermatids
      on day 9.5 and at greater intervals, which resulted in nuclear invagination. The
      results indicate that carbendazim induces abnormalities in spermatid morphology
      that are common to those reported in testes treated with several chemical
      compounds and in testes of mutant animals.

PMID- 9281848
TI  - Ethanol production from spent cherry brine.
AB  - Spent cherry brine is an acidic byproduct of maraschino cherry processing and
      typically consists of variable amounts of glucose and fructose of up to 11%
      fermentable solids, 0.5-1.5% CaCl2, up to 0.4% sulfur dioxide, sorbitol, and
      lesser amounts of other cherry constituents. Disposal of brine represents a
      significant cost to processors because of its high biological oxygen demand. As
      an alternative, brine was tested as a substrate for ethanol production.
      Initially, the toxic level of sulfur dioxide was reduced by raising brine pH to
      8.0 to precipitate calcium sulfite. Because alkalinization was subsequently found
      to result in a 10-fold reduction in phosphorous, brines were titrated with
      phosphoric acid to pH 6.0 prior to inoculation with Saccharomyces cerevisiae. All
      strains of Saccharomyces cerevisiae tested were able to ferment all lots of
      Ca(OH)2-treated and phosphorous-enriched brines efficiently. One lot of brine
      containing 10% (w/v) fermentable sugar yielded 4.7% (w/v) ethanol in 4 days.

PMID- 9281849
TI  - Analysis of a commercially improved Penicillium chrysogenum strain series:
      involvement of recombinogenic regions in amplification and deletion of the
      penicillin biosynthesis gene cluster.
AB  - Several commercially improved strains of Penicillium chrysogenum have been shown
      to carry amplifications of the entire penicillin biosynthesis gene cluster.
      Analysis previously carried out using the strain BW 1890 has here been extended
      to the characterisation of other members of the SmithKline Beecham strain
      improvement series. We have determined the length of the amplicon to be 57.4 kb
      and shown a general increase in copy number and penicillin titre through the
      series. Sequence analyses of the promoter regions of the acvA, ipnA and aat genes
      in the high titre strain BW 1901, and comparisons with wild-type sequences have
      not identified any potentially titre-enhancing mutations. In addition, cDNA
      screening has failed to identify any further transcribed elements within the co
      amplified region. The homogeneity of hybridisation patterns and the
      identification and analysis of a single copy revertant has shown that the
      amplification is of a direct tandem nature and we propose a model of chromatid
      misalignment and recombination as its mode of generation. Hybridisation analysis
      of penicillin non-producing mutants has indicated the loss, in all those
      investigated, of the entire penicillin biosynthesis gene cluster, similarities
      between the deletion junctions in these strains and comparison with previously
      published data indicating the presence of recombinogenic regions flanking the
      penicillin biosynthesis gene cluster.

PMID- 9281850
TI  - Detection and partial characterization of a bacteriocin produced by
      Carnobacterium piscicola 213.
AB  - BLIS 213, is a bacteriocin-like inhibitory substance produced by Carnobacterium
      piscicola 213. It is active against Carnobacterium, Enterococcus and Listeria
      spp. No activity was observed against tested Lactobacillus, Lactococcus,
      Leuconostoc and Pediococcus strains, nor against Gram-negative bacteria. The BLIS
      213 activity was inactivated by several proteolytic enzymes. It was heat
      resistant (121 degrees C for 20 min), and stable over a pH range of 2-8. Activity
      was determined by a dilution micromethod; it was increased after SDS treatment. A
      mutant strain which lacks bacteriocin production was isolated and designated as
      Carnobacterium piscicola 213a. It had the same phenotypic and biochemical
      properties as the parent strain, and was not sensitive to bacteriocin activity.
      The apparent molecular weight of the bacteriocin in the crude extract was greater
      than 10 kDa. It was about 6 kDa after SDS-PAGE of a partially purified
      bacteriocin by adsorption on producer cells. The isoelectric point of the BLIS
      213 was around 9.3.

PMID- 9281851
TI  - Microbial production of a novel trihydroxy unsaturated fatty acid from linoleic
      acid.
AB  - A bacterium isolated from a dry soil sample collected from McCalla, AL, USA,
      converted linoleic acid to a novel compound, 12,13,17-trihydroxy-9 (Z)
      octadecenoic acid (THOA). The organism is a Gram-positive, non-motile rod (0.5
      microns x 2 microns). It was identified as a species of Clavibacter ALA2. The
      product was purified by high pressure liquid chromatography, and its structure
      was determined by 1H and 13C nuclear magnetic resonance and Fourier transform
      infrared spectroscopies, and by mass spectrometer. Maximum production of THOA
      with 25% conversion of the substrate was reached after 5-6 days of reaction. THOA
      was not further metabolized by strain ALA2. This is the first report of a
      12,13,17-trihydroxy unsaturated fatty acid and its production by microbial
      transformation. Some dihydroxy intermediates were also detected. THOA has a
      structure similar to those of known plant self-defense substances.

PMID- 9281852
TI  - Peptide epitope mapping in vaccine development: introduction.
AB  - Protection from infectious disease by the host immune response requires specific
      molecular recognition of unique antigenic determinants of a given pathogen. An
      epitope is an antigenic determinant which: 1) specifically stimulates the immune
      response (either B or T cell mediated); and 2) is acted upon by the products of
      these protective mechanisms. In B cell immunity, antibodies produced from
      stimulation by specific epitopes recognize and bind to these same antigenic
      structures. Identification of protective epitopes is extremely valuable to
      successful vaccine development. In order to be protective these antibodies must,
      in addition to recognition and binding, interfere with some vital step in
      pathogenesis such as adherence or toxin action. Protein B cell epitopes are
      frequently composed of the side chains (R-groups) of the amino acids found at
      solvent-exposed surfaces. These epitopes are classified as continuous (also
      linear or sequential) if composed of a single antibody-recognizing element
      located at a single locus of the primary structure. They are discontinuous (or
      assembled) if more than one physically separated entity is involved. T cell
      epitopes are peptides on the surface of antigen-presenting cells (macrophages,
      dendritic cells, and B cells) that are bound to major histocompatibility
      proteins; the T cell recognizes this peptide-MHC complex.

PMID- 9281853
TI  - Linear epitope mapping of humoral responses induced by vaccination with
      recombinant HIV-1 envelope protein gp160.
AB  - To enhance utility of the linear epitope mapping (Pepscan) technique for assay of
      humoral responses linked to vaccination, two modifications were tested. First,
      peptides were incubated with serum contained in baths rather than individual
      wells. Second, a rigorous statistical model was developed to determine which
      peptide/antibody-binding interactions were significant. The modifications
      increased the ability to detect signal in these experiments by 15- to 45-fold.
      These two modifications were applied to linear epitope mapping of HIV
      seropositive volunteers under treatment with recombinant HIV gp160 and also to
      rabbits immunized with the same product. Changes in fine specificity of response
      were observed in animal models and human vaccine recipients over the course of an
      immunization series with this antigen.

PMID- 9281854
TI  - Linear epitopes of colonization factor antigen I and peptide vaccine approach to
      enterotoxigenic Escherichia coli.
AB  - Enterotoxigenic Escherichia coli (ETEC) cause diarrhea in infants and in
      travelers to developing countries. The bacteria utilize colonization factors (CF)
      for adherence to intestinal epithelia, then release toxins causing diarrhea. CF
      are strong immunogens as well as protective antigens. While 20 ETEC CF have been
      described in the literature, 11 CF are prominent enough to be considered for
      vaccine targeting. Of this group, six of the members fall into the CFA/I family
      of CF. Geysen pin (peptide) linear epitope analysis demonstrated that three
      regions containing linear epitopes exist in CFA/I, and that both B- and T-cell
      linear epitopes of CFA/I were concentrated at the N-terminus of the protein. We
      have determined N-terminal sequence of the CFA/I family members not previously
      sequenced. Comparison of the protein sequence of the six members of the family
      showed a strong homology up to residue 36. A peptide of 36 amino acids
      representing a consensus of the six sequences was synthesized and used to
      immunize animals. The antibody induced to the peptide was reactive to the peptide
      as well as cross-reactive to each member of the CFA/I family in Western blots. In
      addition, this antibody agglutinated three of the six members of the CFA/I family
      when added to whole cells expressing the native CF. We are currently evaluating
      different carriers and conjugation methods to maximize production of high titer,
      agglutinating antibody. It is hoped that this and related research will result in
      an effective and inexpensive cross-reactive and cross-protective ETEC vaccine.

PMID- 9281855
TI  - Mapping epitopes of neutralizing monoclonal antibodies using phage random peptide
      libraries.
AB  - Identification of protective determinants from microbial proteins is a necessary
      step in the rational design of subunit vaccines. We have previously used a
      synthetic peptide scan (Pepscan) assay to map a panel of eight neutralizing
      monoclonal antibodies (mAb; designated as C1.1 to C1.8) to a common motif
      sequence from Chlamydia trachomatis. In the present study, five of the eight mAbs
      were used to screen phage random peptide libraries. mAbs C1.1 and C1.3 selected a
      motif sequence of G-L-X-N-D from a pIII-based phage random peptide library and a
      motif sequence of G-X-X-N-D from a pVIII-based random peptide library while mAbs
      C1.6 to C1.8 failed to select recognizable motifs from either of the phage
      libraries. However, C1.6 to C1.8 bound to the same motif sequence displayed on
      phage when the appropriate conformational constraints were imposed onto the motif
      sequence. Thus the specificity of the mAbs identified on Pepscan assays
      correlates with the mAbs' dependence on local epitope constraints displayed on
      the phage surface.

PMID- 9281856
TI  - Influence of various bile salts on beta-glucuronidase activity of intestinal
      bacteria.
AB  - While the decrease of the beta-glucuronidase activity of sonicated cells of
      Clostridium perfringens and Escherichia coli was obvious for sodium deoxycholate
      (DC), it was not so obvious for other bile salts (sodium glycocholate and sodium
      cholate). The enzyme activity of intact cells of these bacteria was significantly
      enhanced by the presence of DC, but not by the other bile salts in the buffer.
      These results suggest that the permeability of the bacterial cells is increased
      more by the presence of DC than by other bile salts.

PMID- 9281857
TI  - Effects of extracellular products of Vibrio alginolyticus on penaeid prawn plasma
      components.
AB  - The effects of both crude extracellular products (ECP) and a partially purified
      protease of Vibrio alginolyticus on the plasma components of kuruma prawn
      (Penaeus japonicus) and tiger prawn (P. monodon) were studied using crossed
      immunoelectrophoresis (CIE). A component of the plasma, tentatively identified as
      coagulogen, apparently disappeared after incubation with the ECP, while the
      amount of a component tentatively identified as haemocyanin decreased. The
      coagulogen and an unknown component (component 1) in the penaeid plasma showed an
      increased migration rate after incubation with a partially purified 33 kDa
      protease of the bacterium. In contrast, incubation with protease had no
      detectable effect on the amount of haemocyanin. These events may significantly
      contribute to the pathogenicity of Vibrio alginolyticus in penaeids.

PMID- 9281858
TI  - Effect of non-target cells on the sensitivity of the PCR for Escherichia coli
      O157:H7.
AB  - The sensitivity of a multiplex PCR for the virulence factors VT1, VT2 and eaeA
      specific for enterohaemorrhagic Escherichia coli (target cells, T) was adversely
      affected when non-pathogenic E. coli (non-target, NT) cells were present. In the
      absence of NT cells the sensitivity, obtained by decimally diluting the T cell
      culture, was T-10 (< 10 cfu ml-1) for eaeA and VT2, and T-5 (ca 10(4) cfu ml-1 T)
      for VT1 virulence factors. When approximately 10(9) cfu ml-1 NT cells (NT0
      dilution) were present, the sensitivity dropped to T-1, T-3 and T-1 (ca 10(7),
      10(6) and 10(8) cfu ml-1 T) for eaeA, VT2 and VT1, respectively. At NT-1 (ca
      10(8) cfu ml-1 NT) or higher dilutions the sensitivity of eaeA and VT2 was the
      same as when no NT cells were present. In respect of VT1 the sensitivity
      gradually increased until at NT-4 the sensitivity was the same as when NT cells
      were completely absent. This work indicates that caution should be exercised when
      interpreting PCR results particularly when substantial non-target cell
      populations are suspected.

PMID- 9281859
TI  - Utilization of an auxotrophic strain of the yeast Yarrowia lipolytica to improve
      gamma-decalactone production yields.
AB  - gamma-Decalactone is an aroma compound with a pleasant peachy odour. Most
      industrial processes use the bioconversion of ricinoleic acid by yeasts to
      produce gamma-decalactone. Peroxisomal beta-oxidation activity is responsible for
      the bioconversion. Some yeasts, Yarrowia lipolytica in particular, grow during
      the bioconversion, yielding a low bioconversion rate. Auxotrophy for uracil of a
      genetically engineered Y. lipolytica strain was used to prevent growth in the
      bioconversion medium. beta-Oxidation activities and gamma-decalactone production
      of the auxotrophic strain were measured and compared with a wild-type strain in
      media supplemented or not. Induction of beta-oxidation was observed in the non
      supplemented medium, although to a lesser extent than in supplemented medium.
      Aroma productivity of the auxotrophic strain in the supplemented medium was
      similar to that observed for the wild-type strain in both media. However, in the
      non-supplemented medium the productivity of the auxotrophic strain was 10-20-fold
      higher.

PMID- 9281860
TI  - Isolation of Actinomyces viscosus strain GA: characteristics of its cellular
      biological retardant(s).
AB  - Actinomyces viscosus strain GA produces an exocellular biological retardant(s)
      that prevents certain vegetable plants from becoming overgrown. The biological
      retardant(s) was assayed using the etiolated wheat coleoptile assay, and
      fractionation of culture supernatant fluid resulted in a partial purification of
      the retardant(s). The biological retardant(s) was most active around pH 7 in the
      bioassay and when applied to sterile soil mixture. The biological retardant(s)
      was tentatively identified as a derivative of a rare hexose carbohydrate (but not
      an amino sugar) but an exact structure was not determined. In a sterilized
      synthetic soil system, the biological retardant(s) has an effect on tomato
      cultivars similar to that observed by the synthetic plant growth regulators Alar
      (succinic acid 2,2,-dimethylhydrazide) and Bonzi (paclobutrazol).

PMID- 9281861
TI  - Detection of Xylella fastidiosa in potential insect vectors by immunomagnetic
      separation and nested polymerase chain reaction.
AB  - A sensitive and specific assay for detecting Xylella fastidiosa in potential
      insect vectors was developed. This assay involves immunomagnetic separation of
      the bacteria from the insect, followed by a two-step, nested polymerase chain
      reaction (PCR) amplification using previously developed oligonucleotide primers
      specific to X. fastidiosa. A total of 347 leafhoppers representing 16 species
      were captured and sampled from American elm (Ulmus americana L.) trees growing in
      a nursery where bacterial leaf scorch caused by X. fastidiosa occurs. Two of
      these leafhopper species, Graphocephala coccinea and G. versuta, regularly tested
      positive for X. fastidiosa using this technique. These insects are therefore
      potential vectors of X. fastidiosa. Using immunocapture and nested PCR, it was
      possible to detect as few as five bacteria per sample.

PMID- 9281862
TI  - Lipases in autolysed cultures of filamentous fungi.
AB  - Fifty-one fungi from different genera and strains were checked in plate to
      determine lipase activity in protein precipitates from their autolysed cultures.
      Each of them was then analysed at 3.5, 6.5 and 9.2 pH units and, as a
      consequence, basic lipases with high activity at 9.2 pH were found after 1 h of
      incubation. Only 25% of the studied fungi showed this lipase activity, among them
      the best producers were fungi from genus Fusarium (47% of fungi had lipase
      activity). In addition to lipase activity, Fusaria showed a low hydrolytic
      activity on cutin and suberin. The genus Aspergillus produced lipase and cutinase
      activity to a similar extent. Aspergillus nidulans 2544 also showed suberinase
      activity in a considerable amount. Penicillium species had very low activities.
      Other species and strains from genus Trichoderma, order Mucorales and class
      Basidiomycetes, did not show lipase activity in their degradative processes.

PMID- 9281863
TI  - Survey of retail cheeses, dairy processing environments and raw milk for
      Escherichia coli O157:H7.
AB  - Escherichia coli was isolated from 58% (11/19) of retail soft and semi-soft
      cheeses tested, but E. coli O157:H7 was not detected. The presence of E. coli in
      retail cheeses and the lack of baseline data on the prevalence of serotype
      O157:H7 strains prompted us to survey ingredients and the environment in 15
      cheese and dairy plants. Escherichia coli O157:H7 was not detected in any of the
      1104 samples tested, including 42 raw milk samples. These results suggest that
      serotype O157:H7 is not prevalent within dairy product ingredients and processing
      environments.

PMID- 9281864
TI  - The sensitivity of Escherichia coli O157 to some antimicrobials by conventional
      and conductance assays.
AB  - A range of sensitivities exhibited by Escherichia coli O157 to cefixime and
      potassium tellurite are demonstrated. The sensitivity was shown by growth on
      cefixime tellurite sorbitol MacConkey agar and by the effect on the metabolic
      activity in glucuronate trimethylamine-oxide conductance broth. These
      antimicrobials are regularly used in the isolation of this pathogen from food and
      clinical specimens, and such sensitivity may lead to the reporting of false
      negative samples.

PMID- 9281865
TI  - Influence of sporulation medium and divalent ions on the heat resistance of
      Alicyclobacillus acidoterrestris spores.
AB  - The influence of divalent cations on the heat resistance of spores of the
      thermoacidophilic spoilage bacterium Alicyclobacillus acidoterrestris was
      studied. The heat resistance of A. acidoterrestris spores was not affected by the
      presence of the different divalent cations (Ca2+, Mg2+, Ba2+, Mn2+ and Sr2+) in
      the sporulation medium, and by the demineralization or remineralization. And the
      Ca and Mn contents in A. acidoterrestris spores were scarcely changed by these
      treatments. However, the heat resistance of Bacillus subtilis spores was affected
      with the changes of Ca content in the spores. The Ca contents in A.
      acidoterrestris spores of the different forms were greater than the DPA content.
      In contrast, the DPA content in the B. subtilis spores was greater than the Ca
      content. These findings suggest that the presence of constant amount of Ca-DPA
      and a stronger binding characteristic of divalent ions, especially Ca and Mn, is
      reflected in the specific heat resistance of A. acidoterrestris spores.

PMID- 9281866
TI  - Resistant organisms: a dilemma for primary care?

PMID- 9281867
TI  - Aspirin use in middle-aged men with cardiovascular disease: are opportunities
      being missed?
AB  - BACKGROUND: Since the 1980s, clinical trial evidence has supported aspirin use in
      the secondary prevention of cardiovascular disease (CVD). AIM: To explore aspirin
      use among British men with known CVD in a population-based study. METHOD:
      Longitudinal study (British Regional Heart Study), in which subjects have been
      followed up for cardiovascular morbidity and mortality since 1978-1980. Aspirin
      use was assessed by questionnaires to study participants in November 1992 (Q92);
      cardiovascular diagnoses are based on general practice notifications to October
      1992. A total of 5751 men aged 52-73 years (87% of survivors) completed questions
      on aspirin use. RESULTS: Overall, 547 men (9.5%) were taking aspirin daily, of
      whom 321 (59%) had documented CVD. Among men with pre-existing disease, 153 out
      of 345 (44%) men with myocardial infarction, 42 out of 109 (39%) with stroke, and
      75 out of 247 (29%) with angina were taking aspirin daily. Among men with angina
      (54% versus 26%) or myocardial infarction (59% versus 42%), those who had
      undergone coronary artery bypass surgery (CABG) or angioplasty were more likely
      to be receiving aspirin. Higher rates of aspirin use were also found in those
      whose last major event occurred after January 1990 (47% versus 34%). There was no
      association between aspirin use and social class or region of residence.
      CONCLUSION: Despite strong evidence of its effectiveness, many patients with
      established CVD were not receiving aspirin. Daily aspirin treatment was less
      likely in men with less recent major CVD events and in those who had not received
      invasive treatment.

PMID- 9281868
TI  - Assessing the performance of general practices caring for patients with asthma.
AB  - BACKGROUND: General practitioners (GPs) have had to record information about
      chronic disease management and send this to the health authorities since the
      introduction of the new contract in 1990. AIM: To discover the relationship
      between practice emergency admission rates for asthma and the characteristics of
      the practice's patients and chronic disease management programme. METHOD: This
      was an ecological study comparing practice emergency admission rates of asthma by
      general practice with the practice's performance in measuring the prevalence,
      peak flow, and number of patients on regular prophylaxis. In addition,
      prescribing analysis and costing (PACT) data and census linkage were used to
      assign social class to patients and, when aggregated, to practices. The practice
      admission rate was correlated against each of these variables and then the
      relationships were explored in multiple linear regressions. RESULTS: A high rate
      of admission in practices was correlated with deprivation of the patients, in the
      form of a practice Townsend score (r = 0.33, P = 0.003), and also with poorer
      prescribing, measured by the preventer-reliever ratio (r = -0.38, P = 0.001).
      Regression analysis showed that the relationship between good prescribing and low
      admission rates was not explained by confounding variables. Only 32% of the
      variation in admission rates between practices was explained by the regression
      equation. None of the variables recorded in the annual report were significantly
      related to admission rates. CONCLUSION: Annual reports from the practice to the
      health authority are unhelpful in monitoring general practice performance, but
      prescribing, as measured by the preventer-reliever ratio, and hospital admission
      rates have limited usefulness.

PMID- 9281869
TI  - Older people's perceptions about symptoms.
AB  - BACKGROUND: Little is known of the nature and origins of the attitudes that older
      people have towards ageing, disease, and medical treatments. Several studies on
      older people in the community have suggested under-reporting of symptoms. There
      may be several reasons for this, including the possibility that some older people
      regard disease processes as a natural feature of ageing and, consequently, feel
      that medical intervention may have little to offer. AIM: To investigate the
      perceptions of older people about the significance of symptoms and what action
      they would take in response to particular symptoms. METHOD: Thirty-three men and
      77 women attending social clubs (median age 78 years) were opportunistically
      selected and assessed using a supervised questionnaire. RESULTS: Many symptoms
      classically associated with common diseases were often considered to represent
      disease as well as to be normal for old people. Most would consult a doctor if
      they were to experience them. Some important symptoms, such as blackouts or
      paralysis of a limb, were not considered to be normal. Non-specific symptoms of
      psychiatric disturbances were also frequently considered normal but were not
      considered to represent disease. Whether or not a doctor would be consulted was
      often, but not always, related to whether a symptom was thought to represent a
      disease. Consulting a pharmacist was seldom considered appropriate. CONCLUSIONS:
      Doctors working with elderly people need to consider how beliefs about health and
      disease might affect what is reported to them. Specific enquiry needs to be made
      about symptoms of psychiatric disturbances. These findings suggest that there is
      a case for increased health education at retirement age.

PMID- 9281870
TI  - Use of betel quid and cigarettes among Bangladeshi patients in an inner-city
      practice: prevalence and knowledge of health effects.
AB  - BACKGROUND: Betel quid chewing, often combined with tobacco chewing, is a common
      habit in the Indian subcontinent. It is associated with the development of
      malignancy of the oral mucosa and foregut. Among Asian communities in the United
      Kingdom (UK), Bangladeshis are particularly likely to retain this habit. AIM: To
      investigate the prevalence of betel quid chewing, smoking, and knowledge of
      health hazards associated with these habits among the Bangladeshi population in
      an east London general practice. METHOD: A bilingual postal questionnaire to all
      306 adults (25 years and over) identified as being of Bangladeshi origin within
      one practice in east London. RESULTS: The questionnaire response rate was 46%.
      The prevalence of betel quid chewing was over 80% with no sex difference. Men
      were more likely to smoke tobacco than women (men = 57%, women = 11%, X2 = 33.3,
      P < 0.001), but over half the women added tobacco to their quid for chewing.
      Whereas over 80% of both male and female respondents identified the health risk
      of smoking, only one third identified oral cancer as a risk. In all, 25% of
      respondents started chewing in the UK. CONCLUSIONS: The low response rate is
      discussed. The findings indicate that the majority of Bangladeshi respondents are
      unaware of the health risks of a common social habit, although well informed
      about smoking risks. A government health warning should be introduced for betel
      quid sold in the UK.

PMID- 9281871
TI  - Dog bites in Bosnia.
AB  - BACKGROUND: Rabies is a zoonosis that remains endemic in most parts of the world.
      Primary care physicians are in the first line of defence against the disease. An
      increasing number of British practitioners and medical students are being exposed
      to the dangers of rabies through humanitarian work on overseas attachments.
      Rabies is enzootic throughout Bosnia-Herzegovina and presents a hazard to the
      multinational troops currently deployed there. AIM: To describe the British
      Army's experience of animal bites and rabies prevention in Bosnia during the
      first six months of its current peace enforcement mission, and to make general
      recommendations on the good management of any rabies hazard at primary care level
      and under field conditions. METHODS: Routine data from the Army's epidemiological
      database (ARRC 97) were reviewed, and theatre issues of rabies vaccine and immune
      globulin were used as a proxy measure for administered post-exposure prophylaxis.
      RESULTS: A total of 62 animal bites were reported in British troops between
      December 1995 and May 1996, of which 28 were unprovoked bites and resulted in the
      administration of a course of rabies vaccine. Ten of these were severe bites and
      rabies immune globulin (RIG) was administered in addition. The total cost of
      rabies post-exposure prophylaxis was US$6914.00. CONCLUSION: The prevention of
      rabies has major human and resource implications, and primary care staff involved
      in rabies post-exposure management need to be well supported in their clinical
      decision-making. Rabies protocols should be clear and unambiguous. The effective
      medical surveillance of military or humanitarian missions in rabies-enzootic
      areas must include the prompt reporting of animal bites. The predeployment
      training of medical teams should include an up-to-date assessment of the local
      rabies threat.

PMID- 9281872
TI  - Accuracy of routinely collected clinical data on acute medical admissions to one
      hospital.
AB  - Despite the rapid growth in routine computerized data collection within the
      National Health Service (NHS), and the increased use of such data for generating
      hospital statistics and doctor activity rates, few validation studies exist.
      During a study of 158 acute medical admissions, and examination of hospital data
      revealed numerous and systematic inaccuracies. If general practitioner (GP)
      performance statistics are to be reliably based on such sources, data validation,
      staff training, and protocols for data entry should form a routine part of NHS
      practice.

PMID- 9281873
TI  - Postpartum HELLP syndrome after a normotensive pregnancy.
AB  - Severe pre-eclampsia, associated with HELLP syndrome, can occur after a normal
      delivery and birth in a woman whose blood pressure has remained normal throughout
      the antenatal period. Although rare, the syndrome can lead to pulmonary oedema or
      renal failure, and should be borne in mind when a woman develops epigastric or
      right upper-quadrant pain after a normal pregnancy and delivery. A significant
      fall in the platelet count in the antenatal period may be a useful indicator of
      risk.

PMID- 9281874
TI  - The grieving adult and the general practitioner: a literature review in two parts
      (Part 1).
AB  - This article is the first of a two-part literature review on bereavement. In part
      1, those psychological theories that have improved the understanding of the
      bereavement process are summarized. In addition, the research examining the
      mortality and morbidity following a bereavement is critically analysed.

PMID- 9281875
TI  - Evidence-based medicine and general practice.
AB  - Evidence-based medicine (EBM) aids clinical decision making in all fields of
      medicine, including primary care. General practice is characterized by particular
      emphasis on the doctor-patient relationship and on biomedical, personal and
      contextual perspectives in diagnosis. Most evidence available to general
      practitioners (GPs) addresses only the bio-medical perspective and is often not
      directly applicable to primary care, as it derives from secondary or tertiary
      care. Emphasis on the biomedical domain and the randomized controlled trial (RCT)
      alone reflects a reductionist approach that fails to do justice to the philosophy
      of general practice. The art of medicine is founded on context, anecdote, patient
      stories of illness and personal experience, and we should continue to blend this
      with good quality and appropriate research findings in patient care.

PMID- 9281877
TI  - Towards effective mentoring in general practice.
AB  - In South Thames, a three-year feasibility study was designed to explore the
      potential contribution of mentors in furthering professional development and
      increasing a sense of well-being among general practitioners. The study led to
      the establishment of an ongoing mentor project as a South Thames (West) Regional
      initiative, funded by the Postgraduate Dean of General Practice. This paper
      outlines the project's structure and administration. The concept of the holistic
      mentor model, together with a strategy (the reflective cycle) for purposeful
      intervention, is also described. The findings from the evaluation of the study
      illustrate the response of doctors to their mentor training, their early
      experience of taking on the role of mentor, and their reporting of the experience
      of those being mentored (the mentees). The issues relevant to the future of
      mentoring are commented on, to inform and encourage further discussion.

PMID- 9281876
TI  - Training for systemic general practice: a new approach from the Tavistock Clinic.
AB  - A new course at the Tavistock Clinic offers general practitioners (GPs) and
      primary care nurses a training based on family therapy principles but directed at
      developing skills and conceptualization across the whole range of general
      practice work. The course may point to a new way forward for postgraduate
      training in general practice, creating links with the social sciences and giving
      doctors and nurses appropriate training for the 'postmodern' world.

PMID- 9281878
TI  - Topical chloramphenicol: have GPs cried halt?

PMID- 9281879
TI  - Six months' experience of the new practice-based patients' complaints procedure.

PMID- 9281880
TI  - Evidence-based general practice.

PMID- 9281881
TI  - Hormone replacement therapy for osteoporosis prevention.

PMID- 9281882
TI  - Mental health care training priorities.

PMID- 9281883
TI  - Mental Health care training priorities.

PMID- 9281884
TI  - OTC prescribing.

PMID- 9281885
TI  - Assessing for audit.

PMID- 9281887
TI  - Management of hypertension.

PMID- 9281886
TI  - Assessing for audit.

PMID- 9281888
TI  - General practice: additional services.

PMID- 9281889
TI  - Ethnicity and paediatric referral in Amsterdam.

PMID- 9281891
TI  - Pharmacokinetics of [14C] BBR 3053, an alkylating bisphosphonate, after single
      i.v. and multiple s.c. administration in rats.

PMID- 9281890
TI  - The in vitro binding kinetics of cisplatin to human plasma proteins is not
      affected by glutathione.

PMID- 9281892
TI  - Lipid peroxidative markers of inflammation in synovial fluid from rheumatoid
      patients.

PMID- 9281893
TI  - Simultaneous determination of ITF 296 and two metabolites in plasma by a
      validated HPLC method.
AB  - A simple and sensitive HPLC validated method was developed for the simultaneous
      determination of ITF 296 (a new orally active nitrate) and its metabolites ITF
      1124 and ITF 1577 in biological samples. Quantitation was performed by peak
      height ratios between the three compounds and the internal standard (ITF 1721).
      Detection limit of the method was 0.005 microgram/ml using 1 ml of plasma. The
      results indicated that the method is reproducible, accurate, precise, sensitive
      and specific for the measurement of the three compounds in plasma samples. Those
      characteristics allowed us to conclude that the method is suitable for analysing
      samples obtained after administration of ITF 296 to humans at therapeutic dosage
      and to animals for formulation studies.

PMID- 9281894
TI  - Chloroquine therapy reduces oestrogen production in females.
AB  - In this study: it has been shown that chloroquine therapy reduces both
      testosterone and oestradiol secretion in females. This reduction was marked the
      longer the duration of exposure to the drug. The animals did not regain the
      pretreatment sex hormone levels even after they were left for one month to
      recover without chloroquine intake. It seems that the inhibitory effect of
      chloroquine is mediated through the production of epidermal growth factor (EGF).
      This latter exerts an inhibitory effect on the LH Lutenzing hormone receptors in
      ovarian granulosa cells. EGF has also got a suppressive effect on 17 a
      hydroxylase enzyme; a key enzyme which is necessary for the hydroxylation of
      pregnenolone and progesterone in the ovary Hydroxy pregnenolone is a precursor of
      androstendione, while 17 a-hydroxyprogesterone is a precursor of testosterone.
      Both androgens (androstendione and testosterone) are aromatized to oestrogens in
      the gonadal and extragonadal tissues. This study draws the attention to prolonged
      chloroquine therapy in collagen disorders. In such diseases as the drug is used
      on long term basis, it should be used with utmost care specially in old female
      patients who are already candidates for oestrogen hormonal replacement therapy to
      protect their fragile status.

PMID- 9281895
TI  - Isolation and characterization of Guiera senegalensis J.F.Gmel. active
      principles.
AB  - A combination of thin-layer chromatography, high-performance liquid
      chromatography, UV spectroscopy and NMR spectrometry techniques for analysis of
      flavonoid content of Guiera senegalensis J.F.Gmel. (Combretaceae) leaves is
      described. Four components, catechin, myricitrin, rutin and quercetin were
      evidenced and determined by HPLC.

PMID- 9281896
TI  - The influence of additives on physical properties of emulsions prepared using
      lecithins and non-ionic surfactants.
AB  - Several oil-in-water submicron emulsions stabilized with unsaturated and
      saturated lecithins or non-ionic surfactants and were prepared in presence of
      various tonicity agents and related substances used as cryoprotectants. Their
      physical properties before and after thermal stress was investigated. Egg yolk
      lecithins required glycerol as tonicity agent when the emulsions will be heated,
      while soy bean lecithin stabilized emulsions could be isotonized by various non
      electrolytes. The addition of co-surfactants e.g. oleic acid and deoxycholic acid
      did not improve the heat resistance of emulsions prepared with egg yolk lecithin
      and sorbitol.

PMID- 9281897
TI  - The relaxant effect of diazepam on rat tracheal strips.
AB  - The effect of diazepam was studied on the rat isolated trachea precontracted with
      acetylcholine 10-3M. Diazepam induced a dose dependent relaxant effect EC50
      values 2.02 +/- 0.28.10(-4)M in controls (n = 38). The effect of diazepam was not
      modified by flumazenil (10-(6) to 10-(4) M) or RP 52028 (10-(6) to 10-(4)M) which
      are antagonists of central and peripheral benzodiazepines receptors respectively.
      No antagonism was observed between diazepam and nucleotides or endogenous ligands
      (adenosine 10(-6) to 10(-4)M, UTP 10(-6) to 10(-4)M, hematoporphyrin 10(-5) and
      10(-4)M or nicotinamide 10(-5) and 10(-4)M). These results excluded an endogenous
      ligand-mediated interaction between nucleotides and diazepam. Propranolol (10(
      7)M) did not modify the diazepam-induced relaxation, which excluded an
      involvement of beta receptors in diazepam relaxation. Theophylline (10(-7) and
      10(-6)M), IBMX (10(-5) and 10(-4)M) rolipram (10(-5) and 10(-4)M) and siguazodan
      (10(-6) to 10(-4)M) displayed to the left the concentration-response curves to
      diazepam. The adenylcyclase activator forskolin (10(-7) to 10(-5)M, the beta
      adrenor stimulant isoprenaline (3.10(-5)M) and the direct acting G stimulant NaF
      (10(-3)M) also produced a leftward shift in the diazepam concentration-response
      curve. The relaxant concentration-effect curves to isoprenaline and to sodium
      nitroprusside were shifted to the left in a concentration-related manner by
      diazepam. Diazepam was more potent on the isoprenaline than on nitroprusside
      induced relaxation. These results suggest that the diazepam-induced relaxation in
      the rat isolated trachea is mediated by an inhibition of cyclic nucleotide
      phosphodiesterases.

PMID- 9281898
TI  - History of therapy of plant viral diseases.
AB  - Sixty years of therapy of virus-infected plants have been examined by analyzing
      the development of therapeutic techniques which have been successful, i.e.
      thermotherapy, chemotherapy and meristem tip culture. The reasons that gave rise
      to the practice of combining techniques have also been investigated. The results
      have only slightly improved our knowledge of virus biology, but have made
      possible the micropropagation of marketable virus-free germoplasm.

PMID- 9281899
TI  - Simulation of protein evolution: evidence for a non-linear aminoacidic
      substitution rate.
AB  - Protein evolution is characterized by several processes. In the theory of neutral
      evolution the rate of mutation is considered a linear process in which the amount
      of aminoacidic substitutions in proteins is constant in time. A simulation
      approach has been developed by using a model of amino-acidic substitution. The
      frequency of spontaneous mutations has been assumed to be equal to about 10(
      9)/base/year. The aim of the present work is to show that starting from a
      constant mutation rate (nucleotide substitutions) the corresponding process of
      aminoacidic substitutions becomes non-linear if some criteria of mutation
      selection are introduced. The basic criteria used are the physical-chemical
      characteristics of aminoacids, the same criteria that have made it possible to
      classify aminoacids. Different classifications based on differences in such
      criteria give different results, indicating that the degenerate nature of the
      genetic code determines a non-linear behaviour of protein evolution. Simulations
      have been performed on short protein subsequences of five aminoacids. A further
      analysis has been made to verify, on the basis of the code structure and of
      accepted selection criteria, the mechanisms of aminoacidic substitutions and the
      existence of preferential paths. We have concluded that aminoacidic substitution
      is not a simple stochastic process, but that complex Markov's chains are
      involved. The consequences are important, although generally ignored.

PMID- 9281900
TI  - Delayed luminescence from simple biological systems.
AB  - Photoinduced ultraweak photon emission in the seconds time range from several
      living organisms is described. Some characteristics of this phenomenon and its
      dependence on some physical parameters are discussed. Some experimental evidence
      of the connection between this phenomenon and the functional state of the
      biological systems is reported.

PMID- 9281901
TI  - The "Nobel": Prize and swindle. The betrayed testament.

PMID- 9281902
TI  - Penetration of host cell lines by bacteria. Characteristics of the process of
      intracellular bacterial infection.
AB  - A model which describes the characteristics of the penetration of the cells by
      bacteria is presented. Since the process of invasion is preceded necessarily by
      the step in which the bacteria adhere to the cells, the proposed model is based
      on the expressions previously derived for the process of adhesion, which allow us
      to determine the number of attached bacteria under different conditions. Thus,
      the model considers that invasion occurs irreversibly from attached bacteria to
      specific receptors located on the cell surface with a rate coefficient = ki so
      that the invasive capacity in a given bacterium-host cell system is mainly
      determined by the value of this coefficient. Once internalized, the bacteria can
      follow three different time courses, namely: 1) intracellular growth is hindered
      so that the bacteria remain in stationary phase, 2) there is a lag phase during
      which the bacteria stay in stationary phase before they are able to grow
      exponentially with a rate coefficient = kc, and 3) the bacteria exhibit a growth
      exponential phase as they enter the cells. In turn, the time course followed by
      extracellular bacteria also has a decisive influence on the process of invasion
      and, in this regard, unbound bacteria are considered either in stationary or in
      exponential phase. Expressions for these different situations have been derived,
      and from them, procedures to determine the levels of bacterial infection and for
      quantitative invasive data analysis are presented.

PMID- 9281903
TI  - Virus load and antigenic diversity.
AB  - In this paper, we analyse mathematical models for the interaction between virus
      replication and immune responses. We show that the immune system can provide
      selection pressure for or against viral diversity. The paper provides new
      insights into the relationship between virus load (=the abundance of virus in an
      infected individual) and antigenic diversity. Antigenic variation can increase
      virus load during infections, but the correlation between load and diversity in
      comparisons among different infected individuals can be positive or negative,
      depending on whether individuals differ in their cross-reactive or strain
      specific immune responses. We derive two models: our first model applies to any
      replicating parasite that can escape from immune responses; our second model
      includes immune function impairment, and specifically describes infections with
      the human immunodeficiency virus (HIV).

PMID- 9281904
TI  - A new measure of xenobiotic toxicity to the fist-line human defence system from
      the time-resolved phagocyte luminescence.
AB  - A new measure of toxicity based on stochastic modelling of single photon-counting
      processes, representing time-resolved phagocyte luminescence of xenobiotic
      perturbed human neutrophils, has been constructed. The stochastic measure of
      toxicity has been verified by the QSAR method, and then compared and contrasted
      with the traditional toxicity measure used in bio- and chemiluminescent research.
      Phenol and benzene homologues were chosen as perturbers due to their importance
      from the viewpoint of ecotoxicity and occupational medicine.

PMID- 9281905
TI  - On the validity of the dispersion model of hepatic drug elimination when
      intravascular transit time densities are long-tailed.
AB  - The dispersion model with mixed boundary conditions uses a single parameter, the
      dispersion number, to describe the hepatic elimination of xenobiotics and
      endogenous substances. An implicit a priori assumption of the model is that the
      transit time density of intravascular indicators is approximately by an inverse
      Gaussian distribution. This approximation is limited in that the model poorly
      describes the tail part of the hepatic outflow curves of vascular indicators. A
      sum of two inverse Gaussian functions is proposed as an alternative, more
      flexible empirical model for transit time densities of vascular references. This
      model suggests that a more accurate description of the tail portion of vascular
      reference curves yields an elimination rate constant (or intrinsic clearance)
      which is 40% less than predicted by the dispersion model with mixed boundary
      conditions. The results emphasize the need to accurately describe outflow curves
      in using them as a basis for determining pharmacokinetic parameters using hepatic
      elimination models.

PMID- 9281906
TI  - Dynamics of human milk extraction: a comparative study of breast feeding and
      breast pumping.
AB  - We describe a mathematical model of the flow and deformation in a human teat. Our
      aim is to compare the theoretical milk yield during infant breast feeding with
      that obtained through the use of a breast pump. Infants use a peristaltic motion
      of the tongue, along with some suction, to extract milk, whereas breast pumps use
      a cyclic pattern of suction only. Our model is based on quasi-linear
      poroelasticity whereby the teat is modelled as a cylindrical porous elastic
      material saturated with fluid. We impose a cyclic axial suction pressure
      difference across the teat and impose a radial compressive force moving along the
      teat which mimics infant suckling. This is compared to the case of cyclic and
      steady pumping only which models the action of breast pumps. The results
      illustrate that there is an optimal time to apply the compressive force during
      the suction cycle that will increase the flow rate in our theoretical teat. The
      model and results may be of use in the future design of effective breast pumps.

PMID- 9281907
TI  - The "clustered structure" of the purines/pyrimidines distribution in DNA
      distinguishes systematically between coding and non-coding sequences.
AB  - A method allowing to measure the inhomogeneous distribution of
      purines/pyrimidines in nucleotide sequences is developed. We show that this
      measure relates to the coding or non-coding character of the considered sequence.
      Coding sequences present a near to the random Pu or Py distribution. This
      property is shared by both protein-coding DNA and functional RNA-coding DNA. Non
      coding sequences present a highly clustered inhomogeneity. We propose the
      hypothesis, corroborated with appropriate computer simulations, that this is due
      to the action of various transposition events accumulated for long time periods.

PMID- 9281908
TI  - The effect of shear stress on solitary waves in arteries.
AB  - In the present work, we study the propagation of solitary waves in a prestressed
      thick walled elastic tube filled with an incompressible inviscid fluid. In order
      to include the geometric dispersion in the analysis the wall inertia and shear
      deformation effects are taken into account for the inner pressure-cross-sectional
      area relation. Using the reductive perturbation technique, the propagation of
      weakly non-linear waves in the long-wave approximation is examined. It is shown
      that, contrary to thin tube theories, the present approach makes it possible to
      have solitary waves even for a Mooney-Rivlin (M-R) material. Due to dependence of
      the coefficients of the governing Korteweg-deVries equation on initial
      deformation, the solution profile changes with inner pressure and the axial
      stretch. The variation of wave profiles for a class of elastic materials are
      depicted in graphic forms. As might be seen from these illustrations, with
      increasing thickness ratio, the profile of solitary wave is steepened for a M-R
      material but it is broadened for biological tissue.

PMID- 9281909
TI  - A left-ear advantage for forced-choice judgements of melodic contour.
AB  - Listeners heard a sequence of five tones presented monaurally, and then made a
      forced-choice judgement about the sequence's contour (i.e., its pattern of upward
      and downward shifts in pitch between successive tones). The forced-choice method
      ensured that contoured judgements were independent of absolute-pitch an interval
      cues. Performance was better for sequences presented to the left ear (right
      hemisphere) than it was for sequences presented to the right ear (left
      hemisphere). This finding provides support for claims of a right-hemisphere bias
      for the processing of melodic contour.

PMID- 9281910
TI  - A lateralized comparison of handedness and object proximity.
AB  - This study was motivated by the emerging hypothesis that right-handers are more
      strongly lateralized and perform better on various aspects of functional
      asymmetry than do left-handers. Right- and left-handers were observed for hand
      selection responses to a unimanual task of reaching for a small cube in positions
      of right- and left hemispace, prompting hemispheric decision-making related to
      hand dominance and attentional (visuospatial) stimuli. As predicted, left-handers
      did not respond with their preferred limb as consistently across positions as did
      right-handers. Additional inspection of the task suggests that being lateralized
      may not be a disadvantage in this context, and that environmental influence may
      play a significant role in hand selection for a particular motor event.

PMID- 9281911
TI  - Freedom of Information Acts and healthcare.

PMID- 9281912
TI  - Coalition building in the legislative arena.

PMID- 9281913
TI  - From this point in time: some memories of my part in the history of anesthesia-
      John S. Lundy, MD.

PMID- 9281914
TI  - Benchmarking: friend or foe.

PMID- 9281915
TI  - A process: development of a model multiculturalism curriculum designed for
      mobility across geographic borders.
AB  - The Council on Accreditation Project, Nurse Anesthesia Educational Requirements
      and Mobility Between North American Free Trade Agreement (NAFTA) Countries, has
      as one of its outcomes the development of a model curriculum that would minimize
      educational barriers for mobility of nurse anesthetists across NAFTA geographical
      borders with a focus on the blending of professional and technical expertise with
      issues of human diversity and/or cultural differences. The overall long-term
      outcome of the project is to test a process. The manuscript discusses the process
      used in year III of the project to integrate cultural concepts into a nurse
      anesthesia model curriculum.

PMID- 9281916
TI  - The utilization of automated ST segment analysis in the determination of
      myocardial ischemia.
AB  - Perioperative cardiac morbidity is a recognized complication of anesthesia and
      surgery. Morbidity includes myocardial infarction, new onset of unstable angina,
      congestive heart failure, and arrhythmias. Almost one third of all patients
      undergoing noncardiac surgery may be at increased risk of cardiac complications
      by virtue of age, coronary artery disease (CAD), or presence of two or more risk
      factors for CAD. Although postoperative ischemia has been identified as a
      significant risk factor for morbidity, automated ST segment analysis systems
      available with the new generation bedside monitors have not been used to identify
      ischemic episodes in patients recovering from anesthesia. Twenty-eight patients,
      age 41 to 80 years, were monitored in the postanesthesia care unit for ST segment
      changes (mean monitoring period, 97 minutes). Four patients had ischemic episodes
      from 7 to 44 minutes, and two of these patients had subsequent postoperative
      morbidity. All episodes were clinically silent. Automated ST segment analysis is
      an easily used technology that shows promise as a means of early detection of
      clinically silent perioperative myocardial ischemia.

PMID- 9281917
TI  - Anesthesia providers' interventions during cataract extraction under monitored
      anesthesia care.
AB  - In 1993 Medicare paid more money to anesthesia providers for cataract surgery
      than for any other surgical procedure. Patients undergoing cataract surgery often
      receive monitored anesthesia care (MAC). Thus, cuts in anesthesia payments from
      Medicare for cataract surgery may be forthcoming. If few interventions were being
      done after a retrobulbar block was placed, then a registered nurse might be a
      safe alternative to an anesthesia provider to monitor the patient. The goal of
      this study was to describe interventions of anesthesia providers during cataract
      extraction after the placement of a retrobulbar block. Anesthetic records were
      reviewed for 560 consecutive cases of cataract extraction using MAC at a large
      tertiary medical center. Anesthesia providers performed interventions (e.g.,
      administration of drugs) on 33% of patients after the retrobulbar block was in
      place (95% confidence bound, < 36%). In conclusion, insufficient evidence exists
      for managed care organizations or other groups to justify a change in practice
      toward a registered nurse monitoring patients undergoing cataract extraction with
      a retrobulbar block. Furthermore, until a prospective randomized study has been
      done, such organizations lack justification for decreasing the amount of time
      that anesthesia providers spend caring for such patients undergoing cataract
      extraction.

PMID- 9281918
TI  - The effect of acrylic nails on the measurement of oxygen saturation as determined
      by pulse oximetry.
AB  - Pulse oximetry (Spo2) is a simple, noninvasive method that is widely used to
      determine oxygen saturation in patients undergoing surgical procedures.
      Artificial acrylic nails have recently become fashionable to strengthen and
      lengthen nails. This study investigates the effect of unpolished acrylic nails on
      the measurement of oxygen saturation by pulse oximetry. Data were collected
      during a 3-month period. Thirty women, average age 32 years (range 18 to 61
      years), were recruited at a high-volume nail salon in northwestern Pennsylvania.
      A baseline pulse oximetry reading was obtained on each subject's natural,
      unpolished fingernail using a Nellcor N-20/N-20P portable pulse oximeter (Nellcor
      Incorporated, Hayward, California). A licensed nail technician applied the
      acrylic compound to the same finger. After the compound had hardened in
      approximately 5 minutes, a second reading was obtained on the unpolished acrylic
      nail. The mean pulse oximetry reading at baseline was 97.33% and after acrylic
      nail application, 97.58%. Using a paired Student's t test, no statistically
      significant differences existed between readings. This study demonstrates that
      unpolished acrylic nails do not affect pulse oximetry measurements of oxygen
      saturation. Patients may not need to remove unpolished acrylic nails before
      surgery.

PMID- 9281919
TI  - The laryngeal mask airway and the emergency airway.
AB  - The laryngeal mask airway (LMA) is an important new tool for managing the
      emergency airway. In a variety of emergency situations, the LMA may be considered
      instead of the face mask or the endotracheal tube. Furthermore, the LMA can be
      used as an aid to intubation and as a bridge to more secure means to control the
      airway. The primary risk with the LMA is aspiration of gastric contents.
      Anesthetists should be familiar with its advantages, risks, indications, and
      uses.

PMID- 9281920
TI  - AANA journal course: update for nurse anesthetists-improving the safety of
      subarachnoid and epidural blocks--Part A.
AB  - Hypotension caused by reduced venous return to the heart is a common hazard
      during subarachnoid and epidural anesthesia. Reduced venous return can also cause
      severe bradycardia and even cardiac arrest. The infusion of a crystalloid
      intravenous preload prior to the injection of local anesthetic helps prevent
      these complications. Unfortunately, intravenous fluid preloading prior to
      subarachnoid or epidural block is neither appropriate for all patients nor is it
      always effective. Vasopressor infusions and lower extremity compression, though
      not completely studied, may allow for further decreases in the incidence of
      hypotension and bradycardia. When dosing an epidural catheter, making each dose a
      test dose and observing for signs of subarachnoid or intravascular injection
      decreases the incidence of hypotension, seizure, and cardiotoxicity. The
      pathophysiology of cardiac arrest and resuscitation is different during major
      conduction block due primarily to changes in peripheral vascular tone and venous
      return to the heart. Neural injury associated with regional anesthesia is due to
      needle trauma, hematoma, injectate toxicity, ischemia, and compression. Though
      neural injury is rare, it is more commonly associated with blocks performed in
      the lumbar region (spinals and epidurals) than in other types of blocks.

PMID- 9281921
TI  - Ethical analysis of arguments supporting the use of certain exclusion criteria in
      organ transplantation.
AB  - The author analyses the arguments put forward by Eike Henner Kluge, in a paper
      entitled "Drawing the Ethical Line Between Organ Transplantation and Lifestyle
      Abuse" (CMAJ, 150 (5), 1994), supporting the idea that nicotine and alcohol
      abusers should not have an equal access to organ transplantation. Referring to an
      egalitarian justice, Kluge argues that one who has caused one's bad health
      condition should not be permitted to compete on the same basis as other
      candidates in order to have access to a scarce health care resource because in
      doing so one penalizes those who are not responsible for their bad health
      condition, diminishing their own chances of obtaining an available organ. After
      considering certain empirical facts in scarce health care resources, particularly
      in organ transplantation, the author defines the main characteristics of a just
      treatment in terms of an equal access to health care and demonstrates that
      Kluge's arguments are not supported by an egalitarian conception of justice. In
      fact, the proposed distribution of services is based on individual merit.

PMID- 9281923
TI  - Canadian Council of Cardiovascular Nurses. Position statement on tobacco and
      health.

PMID- 9281922
TI  - Knowledge and attitudes of critical care nurses regarding organ donation.
AB  - The purpose of this study was to describe the knowledge, attitudes, personal
      commitment, and professional involvement of Canadian critical care nurses in
      organ donation. This was part of a larger study of 4900 Canadian nurses and
      physicians. 50% of nurses receiving questionnaires responded. Of the 147 critical
      care nurses who responded to the survey, over 92% supported organ donation in
      principle. However, only 65.3% had completed organ donor cards. Nurses responded
      correctly to 71.2% of the questions testing knowledge. Attitudes regarding organ
      donation tended to be positive, but 85% of nurses indicated reluctance to
      approach potential organ donors. Critical care nurses scored higher than other
      groups of nurses on the knowledge, attitude, and professional involvement in
      organ donation subscales.

PMID- 9281924
TI  - Informed consent.

PMID- 9281925
TI  - Accessing patients, patient records, and patient databases: the "confidentiality
      access maze", Part I.

PMID- 9281926
TI  - Elderly patients' experiences with nurses guided by Parse's theory of human
      becoming.
AB  - The purpose of this study was to describe the experience of being cared for by
      nurses who are guided by Parse's theory of human becoming from the perspective of
      hospitalized elderly patients. Open-ended interviews were used to collect data
      from a sample of 10 patients. The descriptions obtained from the interviews were
      analyzed using Colaizzi's phenomenological method. Three common themes
      constituted an exhaustive description of patients' experiences of relating to
      their nurses: coming together around instrumental tasks, nurses being there for
      patients, and nurses' pleasing way. These patterns of relating with nurses
      signify that patients felt both cared for and looked after. The findings suggest
      that Parse's theory of human becoming may provide one framework to ensure that
      caring takes place between nurses and their patients. The study has implications
      for nursing practice and research.

PMID- 9281927
TI  - An evaluation of a self-management program for adults with asthma.
AB  - The purpose of this study was to evaluate the impact of a self-management program
      for adults with moderate to severe asthma on compliance with inhaled, prescribed,
      nonemergency medications; asthma symptoms; and airway obstruction. In this
      controlled experimental study, 55 subjects from a rural community were randomized
      to one of two groups. Self-efficacy theory served as the framework for this
      study. Primary measures included the Metered Dose Inhaler (MDI) Chronolog, a
      journal of daily asthma concerns, and a peak-flow meter to appraise airway
      obstruction. Secondary measures included the Asthma Self-Management Assessment
      Tool (ASMAT) and the Self-Efficacy for Asthma Management Scale (SEAMS). These
      measures were completed pre- and post-intervention. Data analysis using
      descriptive and inferential statistics revealed that subjects receiving the self
      management program increased compliance with inhaled medications (U = 271, p =
      .043).

PMID- 9281928
TI  - Diary reports of nausea and vomiting during pregnancy.
AB  - Nausea and vomiting during pregnancy can have a profound effect on the lives of
      some women. Symptoms have been reported across cultures and throughout recorded
      history, but interventions that consistently relieve symptoms have not been
      documented. As part of a larger study, strategies or situations that stimulate or
      relieve nausea and vomiting or retching were evaluated qualitatively.
      Participants (n = 124) who experienced nausea during pregnancy with or without
      vomiting/retching kept a diary for 7 days, recording any interventions or symptom
      relief measures that they used, evaluating the effectiveness of these measures,
      and recording activities or situations that exacerbated their symptoms. Data from
      the diaries were categorized using content analysis. Rest, particularly napping,
      was a measure that was universally employed to relieve symptoms. Participants
      reported that almost any type of sensory perception could stimulate symptoms.
      Sensory stimuli were often exaggerated or altered, with perceptions of odors
      being profoundly affected. Implications for nursing practice are discussed.

PMID- 9281929
TI  - Nurses and the administration of medications. Broadening the focus.
AB  - Nurses administer medications every day as part of their practice. Consequently,
      many studies have explored nurses and the part they play in medication
      administration. The focus of these studies has often been limited, concentrating
      on nurses and drug errors, rather than on incorporating a broader view of nurses
      and the medication administration process in general. In an attempt to broaden
      the focus of the discussion about nurses and medication administration, this
      study used Critical Incident Technique (C.I.T.) to identify registered nurses'
      perceptions of factors affecting the quality administration of medications in
      their practice setting. Five categories of themes emerged as having an impact on
      nurses and the administration of medications: the context, the procedures, the
      groups of professionals involved, the personal attributes of individual staff,
      and the client. Implications of the research for nursing education and practice
      are discussed.

PMID- 9281930
TI  - Improving eating behaviors in dementia using behavioral strategies.
AB  - The purpose of this experimental pilot study was to determine the short- and long
      term efficacy of directed verbal prompts and positive reinforcement on the level
      of eating independence (LEI) of elderly nursing home patients with dementia.
      Twenty-four subjects from a dementia unit were randomly selected and randomly
      assigned to three experimental groups and three control groups. The LEI scale was
      used to measure eating frequency and task performance at six consecutive meals
      during pretest and posttests, T2 and T3. During the treatment phase, which
      consisted of nine consecutive meals, prompts were administered to each
      experimental group and positive reinforcement was given when a subject completed
      eating tasks. Short-term effects were assessed on 2 consecutive days following
      treatment (T2) and long-term effects on 2 consecutive days, 7 days following
      treatment. Significant differences were found in eating performance but not in
      frequency. Experimental groups retained treatment at both posttests. The dementia
      diagnosis should not preclude the possibility that eating skills may be
      reacquired.

PMID- 9281931
TI  - Anticipated outcomes of accidental occupational exposure to HIV.
AB  - This descriptive study surveyed a random sample of 60 registered nurses (R.N.s)
      regarding their perceptions of nine possible consequences of an HIV infection
      resulting from occupational exposure. Areas of highest concern were financial:
      adequacy of workers' compensation and ability of the employer to cover all health
      care costs. Nurses were also concerned about confidentiality and ability to trace
      the event of the occupational exposure. These nurses felt the least threatened in
      the areas of maintaining their housing and the support of family and friends.
      Overall, the responses indicate a great deal of uncertainty surrounding the
      anticipated outcomes of an accidental occupationally derived infection. The
      results suggest clearer communication is needed between nurses and their
      employers regarding their benefits and existing support services.

PMID- 9281932
TI  - Response to Moore's commentary on "Urinary continence changes after hip fracture
      repair".

PMID- 9281933
TI  - The Frontier Nursing Service.

PMID- 9281934
TI  - One-day mastectomy.

PMID- 9281935
TI  - Enteral feeding in the home environment.
AB  - Nutritional status has a major influence on wound healing, immunity, and quality
      of life for home care patients. This article presents the rationale, guidelines,
      and troubleshooting strategies home care nurses can use in caring for patients
      receiving enteral nutrition.

PMID- 9281936
TI  - The Joint Commission on Accreditation of Healthcare Organizations clinical record
      review process.

PMID- 9281937
TI  - Restless legs syndrome in home healthcare.
AB  - Restless legs syndrome affects millions, but most healthcare providers don't know
      it exists. Its sleep-deprived victims are plagued by indescribable crawling
      sensations in their legs that occur at night and that are only relieved by moving
      the legs. Many home healthcare clients, already challenged by their primary
      illness, are also affected by the persistent symptoms of Restless Legs Syndrome.
      It is important that home care nurses learn about Restless Legs Syndrome-what it
      is, how to assess it, and what can be done about it.

PMID- 9281938
TI  - A case of fecal incontinence.

PMID- 9281939
TI  - Humor with hospice clients: you're putting me on.
AB  - The changing healthcare environment is challenging home healthcare nurses to
      rethink what they do and how they do it, and explore innovative approaches to
      improve client satisfaction. This article describes how the nursing intervention
      of humor can be implemented by home healthcare and hospice nurses to provide more
      cost-effective, yet creative, holistic nursing care.

PMID- 9281940
TI  - Communities and home care practice.

PMID- 9281941
TI  - Creative inservices to meet mandatory education requirements.
AB  - To meet the mandates of federal and accreditation bodies, home care organizations
      must be prepared to conduct required education. There is a need to be creative
      and heighten the interest of the staff while doing more with shrinking education
      dollars. This article presents one agency's approach to the annual mandatory
      inservice program that allows the staff to have fun while learning.

PMID- 9281942
TI  - "Real lives": community health nursing practice in today's managed-care
      environment.

PMID- 9281943
TI  - National council recruits CST pilot study participants. Groundbreaking pilot
      study begins next year.

PMID- 9281944
TI  - Using nurse practitioner certification for state nursing regulation: an update.

PMID- 9281945
TI  - Content development of CST cases reinitiated.

PMID- 9281946
TI  - Ask me about CST! A case development committee member's perspective.

PMID- 9281947
TI  - Progress continues on development of the nurse information system database,
      electronic licensure verification information system.

PMID- 9281948
TI  - National council compares two regulatory approaches to the management of
      chemically impaired nurses: an interim report.

PMID- 9281950
TI  - Education and practice: what is the board of nursing role in
      approval/accreditation of nursing education programs?

PMID- 9281949
TI  - National council identifies the functional abilities essential for nursing
      practice.

PMID- 9281951
TI  - Assessing the quality of life of our end-stage renal disease client population.

PMID- 9281952
TI  - Nurse abuse in the Southwestern Ontario Regional Self-Care Dialysis Centre.

PMID- 9281953
TI  - Does flush before fill decrease the incidence of peritonitis in our cycler
      population?

PMID- 9281954
TI  - Presidential report. Chart your course.

PMID- 9281955
TI  - Make the connection.

PMID- 9281956
TI  - Peripherally inserted central catheters. Intravenous Nurses Society.
AB  - The Intravenous Nurses Society (INS) recognizes the need for uniform terminology
      for peripherally inserted central catheters (PICCs) to encourage standardization
      for indications, care, and maintenance strategies for these devices. It also
      recognizes the need for recommendations regarding the choice, use, management,
      and discontinuation of PICCs to promote positive patient outcomes and enhance
      patient comfort, safety, and satisfaction.

PMID- 9281957
TI  - Midline and midclavicular catheters. Intravenous Nurses Society.
AB  - The Intravenous Nurses Society (INS) recognizes the need for uniform terminology
      for midline and midclavicular catheters to encourage standardization for
      indications, care, and maintenance strategies for these devices. It also
      recognizes the need for recommendations regarding the choice, use, management,
      and discontinuation of midline and midclavicular catheters to promote positive
      patient outcomes and enhance patient comfort, safety, and satisfaction.

PMID- 9281958
TI  - Risk management strategies for home transfusion therapy.
AB  - Transfusion therapy has been performed safely in the home setting for the past 15
      years; however, it is not free of risks. Legal liability and risks can be reduced
      when transfusions are performed according to the accepted standards of care.
      Strategies to reduce transfusion risks through administrative, patient care, and
      quality control activities will be discussed. Methods to assure high-quality home
      care services also are provided.

PMID- 9281959
TI  - Management of infectious waste in the home care setting.
AB  - Adaptation of infection control into practical protocol for the home care setting
      continues to present a challenge for home care nurses. Most information published
      on the management of infectious waste in home care is based on hospital
      protocols, and does not apply to home practice. Reasonable practices for disposal
      of infectious waste are not addressed by any authoritative resources. This
      presentation will identify principles of infection control, requirements, laws of
      regulating bodies, and steps that are measured chronologically to write
      administrative waste control policies.

PMID- 9281960
TI  - Controversies in hydrating the terminally ill patient.
AB  - It is a common practice in healthcare to provide comfort and relief from
      distressing symptoms with the use of intravenous fluids when the patient is no
      longer able to ingest an adequate amount of fluid. If hydration is not provided
      to a patient, the medical professional is thought to be negligent of the
      patient's needs, to consign the patient to a horrible death, and even to shorten
      the patient's life. On the contrary, dehydration in terminal illness has not been
      found to produce distressing symptoms or to shorten life span; it may even be
      beneficial.

PMID- 9281961
TI  - Impact of dressing materials on central venous catheter infection rates.
AB  - Transparent, semipermeable, polyurethane dressings have become widely accepted
      for dressing central venous catheter (CVC) insertion sites. However, there have
      been differing results in terms of their association with microbial growth under
      the dressing and the risk of subsequent CVC-associated infection. This study
      describes our positive experience in terms of the impact of a highly permeable
      transparent dressing on CVC-associated infection among patients at our facility.

PMID- 9281963
TI  - Celebrating fathers: it should be more than Father's Day.

PMID- 9281964
TI  - Violence prevention: a community approach.
AB  - Violence among children and adolescents has been elevated to the status of a
      public health problem in the United States today. Pediatric nurse practitioners
      are in a unique position to play a major role in violence prevention. This
      article describes the impact of violence on the preschool child including
      developmental and behavioral issues. Violence prevention must be all-inclusive as
      a routine component of anticipatory guidance for preschool children and their
      families. Ways to integrate violence prevention into a primary care approach are
      addressed. Community-based outreach programs that further buffer the impact of
      violence on these children are discussed.

PMID- 9281965
TI  - Coping with marital separation: smoothing the transition for parents and
      children.
AB  - Divorce is a stressful multistage process that can have long-lasting negative
      outcomes for parents and children. Pediatric nurse practitioners are often the
      first health care professionals to be informed of family transitions. Therefore
      they must be knowledgeable of the impact of divorce on parents and children to
      implement appropriate interventions to enhance coping outcomes in this
      population. This article discusses the effects of divorce on parents and children
      and identifies intervention strategies that can be used by nurse practitioners
      when dealing with separated families. Description of the COPE Program, an
      intervention program recently implemented with parents and young children
      experiencing marital separation, is also highlighted.

PMID- 9281966
TI  - Internet sites of interest to pediatric nurse practitioners.
AB  - This article describes the internet and outlines information on the World Wide
      Web. Connecting to the internet is covered briefly. An evaluation tool for World
      Wide Web sites is described. Selected Internet sites of interest to pediatric
      nurse practitioners are reviewed applying the evaluation tool. A general nurse
      practitioner e-mail discussion group is explained with examples of how electronic
      forums can aid in nurse practitioner practice.

PMID- 9281967
TI  - Eye trauma in children: epidemiology, management, and prevention.
AB  - Eye injuries in children are frequently evaluated by nurse practitioners. The
      child with serious eye trauma is quickly assessed and referred to an
      ophthalmologist. However, many of the cases are managed in the ambulatory
      setting. Appropriate and swift management of eye trauma is essential to ensuring
      optimal outcome for the child. In addition, pediatric nurse practitioners play a
      critical role in educating children, families and the public about the prevention
      of eye trauma, particularly the use of protective eyewear. This article discusses
      the epidemiology, assessment, and prevention of eye trauma in children.

PMID- 9281968
TI  - Tourette syndrome.

PMID- 9281969
TI  - Exercise-induced leg pain.

PMID- 9281970
TI  - Genetic testing: how it is transforming the role of health Professionals and the
      implications for pediatric nurse practitioners.

PMID- 9281971
TI  - Preparing pediatric nurse practitioners for roles in specialty practice.

PMID- 9281972
TI  - Breastfeeding and the employed mother.

PMID- 9281973
TI  - Primary health care in South Africa: private practice nurse practitioners and
      traditional healers form partnerships.

PMID- 9281974
TI  - Quick reference guide for clinicians. Smoking cessation: information for
      specialists. U.S. Department of Health and Human Services.
AB  - This Quick Reference Guide for Smoking Cessation Specialists contains strategies
      and recommendations from Smoking Cessation Clinical Practice Guideline No. 18,
      designed to assist clinicians, smoking cessation specialists, and health care
      administrators/insurers/purchasers in identifying tobacco users and supporting
      and delivering effective smoking cessation interventions. These recommendations
      were made as a result of an exhaustive and systematic review and analysis of the
      scientific literature. The primary analytic technique used was meta-analysis.

PMID- 9281975
TI  - Disorders of the adrenal glands.

PMID- 9281976
TI  - Computer-assisted primary care: stops along the information superhighway.

PMID- 9281977
TI  - Antiretroviral therapy in adults.

PMID- 9281978
TI  - Fetal alcohol syndrome: the nurse practitioner perspective.
AB  - Fetal alcohol syndrome is the leading cause of mental retardation in the United
      States. The tragedy is that while FAS is irreversible, it is 100% preventable.
      FAS is caused by maternal consumption of alcohol during pregnancy. Alcohol is a
      teratogen and acts in different ways to produce physical and central nervous
      system malformations and defects in the developing embryo and fetus. FAS is
      characterized by a history of maternal alcohol ingestion, central nervous system
      dysfunction, growth deficiencies, and specific physical anomalies. Adolescents
      and adults with FAS have behavioral problems that differentiate them from other
      mentally disabled individuals. Nurse practitioners can have an impact on the
      prevalence of FAS by educating clients about FAS and its relationship to alcohol
      consumption. NPs need to carefully identify high-risk women and their partners
      before a pregnancy occurs and assist with interventions to stop active alcoholism
      or alcohol use during pregnancy. NPs have the capability to decrease the severity
      of alcohol's effects during pregnancy through education, counseling, and
      intervention. NPs have the skills to work with case-finding and early
      identification of infants and children who display signs and symptoms of FAS.
      With such case-finding, early identification, and prompt referral to the
      appropriate diagnostic and/or supportive community agencies, individuals with FAS
      can receive timely intervention to minimize the effects of FAS. Adults with
      behavioral problems can be assessed for FAS and referred for appropriate
      assistance as well. Finally, NPs can facilitate public awareness of FAS through
      educational efforts with individuals, families, and communities.

PMID- 9281979
TI  - Managing latex allergy in hospital patients and health-care workers.

PMID- 9281980
TI  - The role of gloves in wound care.

PMID- 9281981
TI  - [Qualitative analysis of nursing care skills].

PMID- 9281983
TI  - [Nursing skills for monitoring patients].

PMID- 9281982
TI  - [Nursing care skills for pain alleviation].

PMID- 9281985
TI  - [Nursing assessment and skills in promoting self-care activities of the
      patients].

PMID- 9281984
TI  - [Nursing skills for family care].

PMID- 9281986
TI  - [Nurses' skills for creating an interdisciplinary cooperative environment].

PMID- 9281988
TI  - [Survey methods for developing nursing research (1)].

PMID- 9281987
TI  - [Interpersonal interactions between demented elderly and family caregivers in
      their home].
AB  - The objective of this study was to clarify the actual status of interactions
      performed at home between demented elders and their family caregivers. An
      inductive qualitative study was conducted by using a grounded theory approach.
      Subjects were 25 elderly individuals with dementia of Alzheimer type, and 28
      caregivers in their family. The study was performed using the participant
      observation and interviews in their homes. Based on a constant comparative
      analysis, results revealed the levels of "certainty" and "maintenance of self" of
      the elders as core variables in interactions between the elders and the
      caregivers. Characteristic interactions were found to fall into three categories.
      The interactions in Category 1 showed caregiver's persistence in potential
      "certainty" of the demented elders. Category 2 was the interactions when the
      uncertainty of demented elders was unquestionable, and category 3 was
      interactions when certainty of demented elders was clear: In the category 1,
      subcategories named "looking for the holes", "digging the holes" and "filling in
      the holes" were found. In the category 2, phenomena named "protection",
      "friction", "harmony" and "resistance" were observed. And the category 3
      contained "equality." The researcher examined and clarified behavioral
      characteristics, the backgrounds, topics and the results of the interactions as
      components of each subcategory. The triggers the transition of categories of the
      interactions were examined. This study also treated the differences produced
      according the levels of dementia and role relations of the caregivers for each
      category. This study revealed a part of actual interactions between the demented
      elders and their caregivers, and a part of the world which demented elders may
      experience in interaction with their caregivers.

PMID- 9281990
TI  - [A study concerning economic evaluation of visiting nursing stations].

PMID- 9281989
TI  - [Time perception, maternal tasks, and maternal role behavior among pregnant
      Japanese women].
AB  - The relationship of time perception, maternal tasks, and maternal role behavior
      was examined in 140 pregnant Japanese women with a short-term longitudinal
      design. A model developed by Rubin provided the conceptual framework for this
      research. The Time Perception Scale. Time Production Method, and the Prefatory
      Maternal Response measured the study variables. Study results revealed
      significant differences in duration of time, time production, maternal-fetal
      attachment, and maternal role behavior before and after quickening(fetal
      movement)occurred. Medium to strong positive relationships among time
      orientation, maternal-fetal attachment, gratification, and maternal role behavior
      were found before and after movement. After quickening, a weak relationship
      between time orientation and duration was found. After controlling maternal-fetal
      attachment and gratification in pregnancy and maternal role, orientation in time
      perception accounted for significant amounts of variance in maternal role
      behavior before and after fetal movement. Results show that the process of
      becoming a mother, which started before quickening, increased in magnitude after
      fetal movement. The function of fetal movement is important in developing
      motherhood. In the process of becoming a mother, cognitive, emotional, and
      behavioral aspects in becoming a mother are inseparable from each other. Future
      orientation of time perception contributes to development of maternal role
      behavior. Having a future orientation during pregnancy may indicate hope or
      positive expectation. Based on these findings, several recommendations were
      proposed: (a)to study further the general process of becoming a mother and the
      role of time perception in developing motherhood, (b)to disseminate information
      to the general public about the process in development of motherhood, (c)to
      construct theory to explain the process of becoming a mother, and(d)to conduct
      future research to clarify the construct of time perception and attachment.

PMID- 9281991
TI  - [Studies on the life course and career development of university hospital's nurse
      executives in Japan].

PMID- 9281993
TI  - [The concept of body image--its expansion and complications].

PMID- 9281992
TI  - [Findings on maternal-fetal attachment and recommendations].

PMID- 9281994
TI  - [Surveys and research (2)--Design of survey research (1)].

PMID- 9281995
TI  - [A comparative study of caregivers of the elderly with dementia between 1982 and
      1991].
AB  - The purpose of this study is to clarify the changes of the caregivers'status with
      comparison of two cross-sectional studies. The subjects were 658 (primary, in
      1982) and 705 (secondary, in 1991) group members of "The Association of Families
      Caring for Elderly Persons with Dementia". The summary of results are as follows:
      1) The mean life span of a person suffering dementia was found to be longer in
      1991 than 1992. 2) In 1991, about 30 percent of the patients in all age groups
      were hospitalized and about 70 percent of the patients were treated at home.
      These facts indicated that the medical facilities had expanded their capacities
      during the 9 year period for receiving the elderly with dementia. 3) Family
      members who wished to live independently supported the idea that care should be
      given by a decreased number of individuals within the family. In that sense, the
      family's power of caregiving was decreased. 4) The range of main caregivers'
      informal social-support-network was remarkably expanded. 5) The more the service
      were expanded, the more the service were utilized by the caregivers. However, the
      quality and the quantity of the services provided are still not sufficient to
      meet the caregivers' need. 6) In balance, the difficulties caregivers used to
      face, seemed to be decreased in 1991.

PMID- 9281996
TI  - [Caregiving situations of families caring for older persons with cognitive
      impairment].

PMID- 9281997
TI  - [Developmental process--family caregivers of demented elderly persons].

PMID- 9281998
TI  - [Analysis of wandering behavior among institutionalized demented elderly].

PMID- 9281999
TI  - [The effects of reminiscence groups for elderly persons with dementia].

PMID- 9282000
TI  - [Communication behavior in demented elderly].

PMID- 9282001
TI  - [Interventions for decreasing agitation in persons with dementia].

PMID- 9282002
TI  - [Surveys and research (3): steps in the survey research process for nursing
      practice].

PMID- 9282003
TI  - [Interpersonal interactions between demented elderly and their caregivers].

PMID- 9282004
TI  - [Practice of activity care for demented elderly patients].

PMID- 9282005
TI  - [Therapeutic drama activity for cognitively impaired elderly persons in a nursing
      home--defining the activity and examining its structure and effects].

PMID- 9282006
TI  - [Actual status of patients showing delirium in the general hospital].

PMID- 9282007
TI  - [Issues in nursing research of body image].

PMID- 9282008
TI  - [Analysis of information services on the Internet developed by 2 nursing
      universities].

PMID- 9282009
TI  - [Infection control systems in the United States: its history and problems].
AB  - The purpose of this study is to review recent literature regarding the role of
      the infection control nurse in the United States. Recent relevant literature,
      published between 1982 and 1995, was selected by using a computerized literature
      search, cumulative index to nursing and allied health literature (CINAHL). Four
      major points in the development of infection control practitioners (ICPs) were
      identified from the literature review: (1) Since the late 1960s the number of
      ICPs had increased continuously, through the Center for Disease control training
      programs, and through training programs developed by members of the Association
      for Professionals in Infection Control and Epidemiology (APIC) at the national,
      regional and local chapter levels. (2) The ICPs became certified upon receiving
      satisfactory results on the infection of 2 years of work in the field of
      infection control, and then are authorized to use the title "CIC". The
      certification was valid for five years and is renewed after the ICP passed a re
      examination. (3) Six duties of the ICP were identified: management, prevention,
      surveillance, identification, education, and research. (4) The cost of health
      care was constantly restructuring the health care delivery system in the United
      States. The ICPs also were influenced by these changes. New challenges facing
      ICPs today were, a) the integration of resources to be shared by infection
      control and quality assurance, b) the change of role from specialist to
      generalist, c) the expansion of their roles in the area of epidemiology.

PMID- 9282010
TI  - [Surveys and research (4). Steps in the survey process for nursing practice (2)].

PMID- 9282011
TI  - [Behavior therapy in urinary incontinence in adults].

PMID- 9282012
TI  - [Developing process of an assessment tool for urinary incontinence].

PMID- 9282013
TI  - [Development of a questionnaire to measure the effect of urinary incontinence on
      female sexuality: a reliability and validity study].
AB  - OBJECTIVES: This study developed a measure of the degree of the effect of urinary
      incontinence on female sexuality and tested the reliability and validity of the
      developed measure. Effect of Urinary Incontinence on Sexuality Questionnaire
      (EISQ). METHODS: The EISQ was developed from a thorough literature review and
      interviews of 20 individuals with urinary incontinence who said their
      incontinence had affected their dyadic relationship. These items were submitted
      to an analysis of content validity. This work resulted in a 28 items
      questionnaire that used a 4-point Likert-type response scale. The reliability and
      validity of the EISQ was tested with 144 women with incontinence who visited out
      patient clinic in six hospitals. RESULTS: Cronbach's alpha as the index of
      internal consistency was high. The EISQ total was 0.90 and alpha ranged from 0.70
      to 0.93 for the six subscales. Six factors each with an eigenvalue greater-than
      or-equal-to-one were extracted from a principal components factors analysis with
      varimax rotation. The cumulative percentage of variance explained by this
      solution was 69.0%. Concurrent validity analyses confirmed our predictions that
      the EISQ scores were related to Patient Incontinence Stress (ISQ-P) scores.
      CONCLUSION: The EISQ proved to be reliable and valid as a self-administered
      measure for assessing the effect of urinary incontinence on female sexuality. The
      EISQ has demonstrated sufficient psychometric properties to warrant continued
      study of other samples and to explore the relationship between EISQ and other
      outcome variables.

PMID- 9282014
TI  - [A study of endogenous-exogenous factors in urinary incontinence and home care
      nursing of the elderly at home].
AB  - The present study was made not only to clarify endogenous factors (physical and
      psychological factor of the subjects) and exogenous factors (caregiver
      residential environment, social assistance) in the urinary incontinence of
      elderly persons at home undergoing public visiting nursing, both by sexes and by
      age-groups [65-74 years (young old), 75-84 years (middle old), more than 85 years
      (old old)], but also to examine nursing care problems at home. The subjects were
      252 elderly persons > 65 years (46.8% of all subjects), who were detected for
      urinary incontinence by incontinence screening examination from among 538
      subjects (224 males, 314 females), who underwent visiting nursing by Public
      Health Centers, and the health and welfare department of intra-metropolitan S
      Ward from April 1992 to August 1994. The screening examination was made via
      visiting interview and hearing by Public Health Nurses in charge, about items for
      examination such as disease, treatment, degree of independency for ADL,
      residence, utilization of social resources. nursing burden sensation, etc. The
      analysis was made comparatively by age-groups and by sexes, as mentioned above.
      The following information was obtained; 1) In terms of the incidence of urinary
      incontinence, female subjects showed higher incidence for higher age-grade
      (36.5%, for YO group, 45.1% for MO group and 61.4% for OO group), and male
      subjects showed higher incidence than female subjects (56.8% for YO group, 54.4%
      for MO group and 74.5% for OO group). 2) A few subjects were found within 3
      months of the onset of urinary incontinence. Incontinence-favorite time zone was
      predominantly the midnight zone of 0-6 o'clock a.m. (23.5-52.2%). Care approach
      by caregiver was predominantly "use of diaper" (52.2-90.2%) and "use of diaper
      even with micturition" represented 30-50%. 3) Endogenous factors involved onset
      of cerebrovascular disease or dementia, narrow range of ADL, symptoms such as
      numbness and pain, bedsores, constipation, low social activity, etc. 4) Exogenous
      factors involved elderly caregiver persons, residual care fatigue sensation,
      inconvenient toilet and other housing condition, etc. 5) Endogenous-exogenous
      compound factors in possible urinary incontinence involved paralysis, contrature,
      social activity, start of visiting for morbid state observational nursing,
      guidance and utilization of social services for YO group, suggesting strong
      factor involving the care rather than physical problems of the subject concerned
      for elder group. From the above, suggestions for the subject concerned were made
      as follows; 1) start of visiting aiming at the prevention and improvement of
      urinary incontinence in early stage of onset of cerebrovascular disease
      (especially for males) or dementia (especially for females) and 2) promotion of
      rehabilitation for tension provocation of pelvic muscular group and enlargement
      of ADL and walking distance, and suggestions for caregiver were made as follows;
      1) giving appropriate advice for excretory nursing at home and 2) assessment of
      the relationship with the subject concerned. From the viewpoint of housing
      environment, reconstruction of such a toilet as is easily usable by both an
      elderly person and its nursing person and from the viewpoint of regional system,
      necessary preparation of 24-hour approach to diminution of nocturnal excretory
      nursing burden was suggested.

PMID- 9282015
TI  - [A study of coping in middle-aged women with urinary incontinence].
AB  - The purpose of this study is to clarify the coping patterns of women with urinary
      incontinence (UI) who visited an incontinence special unit. Nineteen patients
      ranging from 42 to 86 in age were interviewed. When they had met the accidents or
      daily occurrences with UI, their attitudes toward UI were classified into six
      coping patterns. They were "managing of UI", "keeping UI in secret", "asking for
      medical treatment for UI", "asking for support", "accepting UI as a fact or being
      resigned to UI, and "avoiding the fact with UI". All these six coping patterns
      reflect their desire to keep themselves in normal status. They concentrated
      themselves on maintain the normalization so as to keep their self-esteem from the
      threat of UI.

PMID- 9282016
TI  - [An interdisciplinary approach to the assessment and behavioral treatment of
      urinary incontinence in geriatric outpatients].

PMID- 9282017
TI  - [Assessing older women's experience with urinary incontinence].

PMID- 9282018
TI  - [Surveys and research (5): Steps in the survey research process for nursing
      practice (3)].

PMID- 9282019
TI  - [Empowerment in nursing concept analysis and application].

PMID- 9282020
TI  - [Empowerment for the people concerned].

PMID- 9282021
TI  - [Issues in empowerment of individual nurses and nursing team].

PMID- 9282022
TI  - [Self presentation of patients disfigured by head and neck cancer].
AB  - Surgery for maxilofacial cancer is often radical and disfiguring, and therefore
      can have an influence on patient's interpersonal relationship and social
      activities. However, little is known about self-presentation of disfigured
      patients during rehabilitation. This is an inductive and qualitative study based
      on 26 extensive interviews. The results demonstrate that patients with
      disfigurement cope actively with problems in their interpersonal relationship and
      even go through the empowerment process. Self-presentation of the disfigured
      patients consisted of four dimensions: (1)self-evaluation: (2)judgment of others'
      reactions; (3)intention of personal relations and style of self-presentation; and
      (4) concrete self-presentation using six "strategies". Each of the dimensions 1-3
      included several processes that were generally taken in sequence according to
      time after surgery, but also strongly influenced by behaviors of family members
      or medical staff. "Strategies" chosen in dimension 4 depending upon the
      situations in dimensions 1-3 corresponded to the five type of "self-presentation"
      reported by Goffman (1959), except for "letting others be used to the patients",
      which was one of the continuous efforts to overcome their chronic disfigurement.
      Importantly, the patients became confident by focusing upon their chronic
      disfigurement. Importantly, the patients became confident by focusing upon their
      healthy parts such as maxiofacial functions recovered to some degree, and this
      confidence led to the acceptance of disfigurement and further to the expansion of
      their social behaviors.

PMID- 9282023
TI  - [Empowerment in support groups for mothers with small children].
AB  - The purpose of this study was to describe the experiences of new mothers in peer
      support groups. The subjects were 14 mothers, each with children under 12 months
      of age. The mothers were members of one of three support groups either organized
      by public health nurses in a health center or midwives in two birthing centers.
      The data was collected through participant observations and interviews. Analysis
      of the data-the group experiences of mothers-allowed for categorization into
      three areas of support: 1) reassurance of oneself as a mother, 2) gaining power
      to form a relationship with the baby, and 3) reconstruction of one's own personal
      life. Results of the study showed that the support group was a source of
      empowerment for the new mothers. The elements of empowerment are indicated in the
      listed categories.

PMID- 9282025
TI  - [Characteristics of psychosocial nursing care--the dimensions of psychosocial
      nursing care to promote empowerment among patients].
AB  - Nurses provide the psychosocial nursing care to promote the patients'
      empowerment. In spite of recognizing the importance of psychosocial nursing. The
      research reported here is part of a large study designed to explore the
      psychosocial nursing intervention strategies. This part of the study is focused
      on characteristics of psychosocial nursing care as identified by nurses. Research
      design was descriptive and qualitative. Subjects were a convenient sample of
      nurses who have more than 5 years experience and agreed to participate in this
      research. Data was collected through semistructured interviews. Data was recorded
      on a tape and transcribed, then analyzed based on Grounded Theory Approach.
      SUBJECTS: The number of subjects consisted of 39 nurses. The average age and
      duration of clinical experience was 36.6 years old and 12.6 years. RESULT:
      Sixteen of the characteristics of psychosocial nursing to promote the empowerment
      among the patients were identified; 1) respect the patients' decision making, 2)
      clinical judgment from multiple perspectives, 3) predictability, 4) flexibility,
      5) classification of the patients by comparison, 6) monitoring, 7) relief from
      reality, 8) relief from pain and suffering, 9) enhancement of the patients' ego
      strength, 10) nurture of hope, 11) support individualized daily living styles,
      12) encouragement of the patients'own problem solving abilities, 13) respect of
      individuality, 14) self-utilization, 15) self-control based on professional
      identity, 16) utilization of team power. DISCUSSION: Nurses choose from the
      sixteen dimensions of psychosocial nursing and organizing them in order to
      stabilizing the patients' conditions.

PMID- 9282026
TI  - [Surveys and research (6). Steps in the survey research process for nursing
      practice (4)].

PMID- 9282024
TI  - [Empowerment and the nursing administration system].

PMID- 9282028
TI  - Independence day: welfare-to-work partnerships.

PMID- 9282027
TI  - Interview with Dr. Doris N. Starks: nurse managed clinics.

PMID- 9282030
TI  - Work locus of control: the intrinsic factor behind empowerment and work
      excitement.
AB  - A positive focus on empowerment explores the relationship between locus of
      control, work excitement, and receptivity to new information. Concepts related to
      control, mastery, and stress management are explored as they relate to an
      individual's affinity for generative learning, as opposed to adaptive learning.
      Internally oriented, proactive individuals perceive their jobs to be more
      enriched and intrinsically motivating than externally oriented, reactive
      individuals who report low levels of job satisfaction and higher levels of
      perceived powerlessness. Those whose jobs are being changed should be offered
      active participation in those redesign efforts. Internally oriented individuals
      will be more likely to volunteer, and thus to both seek and share information.
      Participation in such change efforts will enhance perceptions of control and
      offer the best chances for job satisfaction and successful redesign outcomes,
      including sustained work excitement among internally motivated employees.

PMID- 9282031
TI  - The role of the nurse manager in ambulatory care: results of a national survey.
AB  - Increasing complexity in ambulatory care settings requires nurse managers who can
      function at higher levels. Little agreement currently exists regarding the role
      expectations and academic preparation needed for nurse managers in ambulatory
      care settings. The majority of surveyed ambulatory care nurse managers (40%) have
      an AD or diploma as their highest level of academic preparation, and have thus
      acquired the majority of their management skills in the practice setting. The
      authors express concern that there are pressures to employ non-nurses as managers
      in ambulatory health care settings and that ambulatory nurse managers are often
      seen as not needing advanced academic preparation. A wide variety of settings
      including university and community hospitals, outpatient departments, physician
      group practices and HMOs, currently employ nurse managers in their
      multidisciplinary ambulatory care sites. The majority of ambulatory care nurse
      managers describe their model of care as either the medical model or the
      functional model.

PMID- 9282032
TI  - Assessing contributors to cost of care in nursing homes.
AB  - In 1994 12.7% of the population was 65 and over, while 10.6% were 85 and over.
      Expenditures for nursing homes reached $72.3 billion in 1994 (much of which is
      tax-supported) accounting for 8.7% of all personal health money spent. Data from
      the 1993 Missouri Medicaid cost reports for 403 nursing homes were reviewed to
      determine differences in costs per resident day (PRD) and discover which factors
      most influenced these differences. Mid-sized facilities with 60-120 beds reported
      the lowest resident-related PRD costs. PRD expenses for aides and orderlies were
      higher in tax-exempt facilities, which was thought to be related to their "more
      altruistic" mission. Investor-owned facilities showed significantly greater
      administrative costs PRD, which may relate to higher administrative salaries and
      fancier offices. The authors suggest further study that would incorporate
      location, occupancy rate, quality of care, case mix, and payer mix data.

PMID- 9282029
TI  - Measuring nursing workload: understanding the variability.
AB  - The authors present a new multifactorial intensity and complexity of care model
      and meta-paradigm that is designed to examine costs, nursing work, and the
      variability in resource use across patients and environments. Relationships were
      observed among four key variables which included patient-nursing condition,
      medical condition, caregiver characteristics and the environment. Patient-nursing
      complexity and medical complexity are commonly measured by nursing diagnosis and
      DRG or Canadian case mix groupings (CMG) respectively. The complexities
      associated with the work environment had been the least previously studied
      factors. Environmental complexity factors include both supply and demand
      dimensions: scheduling and coordination of procedures, multiple and long
      procedures, and characteristics and composition of the caregiver team.

PMID- 9282033
TI  - Determining the cost of care through clinical pathways.
AB  - Using the steps from the first approach, the costing of clinical pathways is
      useful to both the clinical and administrative teams. With knowledge of pathway
      cost, clinicians can plan cost-effective changes in the pathway or consider cost
      factors when deliberating on different approaches to care. Using the patient
      classification system to unbundle the nursing component and using the number of
      nursing hours per day of care provides an opportunity to describe the intensity
      of the pathway in its entirety, and by each day of care. One is provided with an
      opportunity to learn from the cost variances by reviewing the standardized costs
      for the pathway, and the actual cost of care of patients on the pathway provides
      an opportunity to learn from the cost variances. This learning, coupled with the
      clinical variance analysis, can suggest new opportunities for improving care and
      potential cost savings. Lastly, the cost associated with a pathway is useful
      knowledge in negotiating managed care contracts.$

PMID- 9282034
TI  - Collaboration--in a variety of ways--creates health care value.
AB  - This is an opportune time for physician/nurse partnerships as the health care
      community moves from systems that treat sickness to systems that are responsible
      for the health of the community. No one profession has all the answers to the
      problems facing health care today. Providers working collaboratively have the
      potential to find solutions as long as they keep in mind that the patient is the
      ultimate purpose for their being. Value will be added by health care
      professionals who allow consumers better access to information and more
      involvement in their care.

PMID- 9282036
TI  - Taking a fresh look at career planning.

PMID- 9282035
TI  - Leadership principles: lessons learned.

PMID- 9282037
TI  - Pioneering new ways to ensure quality health care.

PMID- 9282038
TI  - Strategies for patient and staff education maximize learning time during an era
      of cost containment and staff reduction.

PMID- 9282039
TI  - ONS strives to ensure and promote multiculturalism.

PMID- 9282040
TI  - Getting started: consumers should know the basics before buying a personal
      computer system.

PMID- 9282041
TI  - How does your institution orient new graduates?

PMID- 9282042
TI  - "Pressure ulcers: collaboration in wound care. Is there a reasonable approach?".

PMID- 9282043
TI  - Heel blood perfusion responses to pressure loading and unloading in women.
AB  - Heel pressure ulcers are significant and costly problems causing suffering and
      potential limb loss from infection and compromised blood flow. Heel blood
      perfusion (HBP) deficits accompanying loading likely affect the skin breakdown
      process, but little is known about the loading and off-loading changes. To
      clarify this issue, combined laser-Doppler Imaging (LDI) and Fluxmetry were used
      to assess HBP before, during, and after 40 minutes of continuous heel loading in
      11 female volunteers (32-60 years). During loading, an initial decrease in HBP
      was followed by a gradual small recovery (p < 0.001). Off-loading resulted in a
      significant hyperemic response with HBP exceeding baseline by a factor of 4.72 +/
      0.63 (p = 0.001) and remaining elevated for about 10 minutes. Spatial LDI data
      showed that hyperemic responses are maximum near the pressure center and diminish
      radially. These results suggest a localized, pressure-related tissue trauma,
      which is compensated for by a substantial hyperperfusion. The dependence (and
      adequacy) of this response on clinical variables including heel pressure and
      duration, limb vascular status, and patient health are unknown. The present
      seminal data and associated methods provide a platform from which these and other
      important clinical parameters can be systematically studied and compared.

PMID- 9282044
TI  - A temporary solution to reverse staging: the skin care evaluation sheet.
AB  - The National Pressure Ulcer Advisory Panel (NPUAP) has published recommendations
      over the last several years against the use of reverse staging to describe the
      healing of a pressure ulcer. Clinical studies have shown that as Stage IV
      pressure ulcers heal to more shallow depths, they do not replace lost muscle,
      subcutaneous fat, and dermis before they re-epithelialize. Instead the defect is
      filled with granulation tissue composed of endothelial cells, fibroblasts,
      collagen, and an extracellular matrix. The Minimum Data Set-2 (MDS-2) is a
      comprehensive assessment tool required to be completed on a quarterly basis in
      all long term care facilities that provide care to Medicare patients. Section M
      of the MDS-2 addresses skin condition and requires that pressure ulcers be staged
      as assessed within seven days of documentation, using the guidelines in that
      section. No mechanism currently exists to document progression of ulcer healing,
      leaving the practitioner no alternative but to restage the ulcer. This article
      presents one facility's effort to acknowledge the NPUAP recommendations, while
      complying with reimbursement screening methods.

PMID- 9282046
TI  - Topical wound product ingredient guide.

PMID- 9282045
TI  - Effect of practice guidelines on therapeutic bed use.
AB  - Therapeutic beds, though clinically beneficial, can prove to be costly if their
      use is not directed. In this research utilization project, the use of therapeutic
      beds in five patient care units and one intensive care unit in a 300-bed acute
      care hospital were evaluated before and after the implementation of practice
      guidelines. Usage time and cost for each patient were measured and compared over
      the same four-month period in 1994 and 1995. Our findings indicated there were no
      significant differences between the two groups with regard to the time patients
      spent on therapeutic beds and the total cost of these beds. The mean time on the
      bed and the mean cost per patient were, however, lower for the practice guideline
      group. It was concluded that even without demonstrating significant differences,
      practice guidelines are a useful tool in providing a standard for nursing
      practice when caring for patients in the acute care setting.

PMID- 9282047
TI  - NANDA nursing diagnoses identification and validation in a neonatal unit.
AB  - OBJECTIVE: To identify the problems nurses encounter in a Neonatal Unit and adapt
      them to the corresponding NANDA (North American Nursing Diagnosis Association)
      diagnostic categories for their validation in our environment. DESIGN: A Nominal
      Group Technique (NGT) was developed to identify the problems that nurses detect
      and solve. Identified problems were catalogued with their corresponding
      diagnostic label using the NANDA diagnostic taxonomy. A concordance study was
      carried out between two observers, using the Kappa coefficient. RESULTS: During
      the study period, 36 different NANDA diagnostic categories were identified for
      use. From these, 5 have been validated with an excellent or good concordance (K >
      0.70) and 2 with an average concordance (0.70 > K > 0.40). The remaining
      categories did not occur with enough frequency during the study period to apply
      statistical treatment. CONCLUSIONS: The diagnostic categories validated in our
      Unit occur frequently, are easily identified by the nurses, and can be used in
      patient care plans. Non-validated categories may become valid in subsequent
      studies.

PMID- 9282048
TI  - Parents' experience of hospitalization: different strategies for feeling secure.
AB  - Twenty parents of boys (ages 2-14 years) hospitalized for hypospadias repair in a
      pediatric surgery department in Sweden, were interviewed concerning their
      experience when their child was hospitalized. A qualitative analysis of the
      interviews indicated that the most important issue to the parents was finding
      security at the hospital. Parents manifested one of three different strategies
      that enabled them to feel secure at the hospital; (a) relinquishing the care of
      their children to the nursing staff; (b) obtaining a measure of control over
      their children's care; and (c) relying on knowing their child best. The parental
      strategy adopted to feel secure was found to correspond with the way parents
      experienced the hospitalization. Differences were found in their children's
      experiences of pain and the alleviation of the pain during the hospitalization.

PMID- 9282050
TI  - Health beliefs and behaviors in rural high school juniors.
AB  - This descriptive study investigated the health beliefs and behaviors of 709 high
      school juniors in two rural counties of Pennsylvania. The Adolescent Wellness
      Appraisal (AWA) was utilized to survey this population in an attempt to
      understand rural adolescent health so that appropriate interventions could be
      implemented. Results demonstrated the presence of the usual adolescent problems,
      such as violence, substance usage, and poor nutritional and exercise habits. It
      also established the presence of a striking number of stressful events, such as
      parental loss and relocation, experienced in just a one year period of time. The
      results of this survey are discussed in relation to those from earlier surveys
      conducted by the AWA, tool creators at the University of Michigan. Overall
      implications suggest the need for greater availability of health promotion in
      rural areas, as well as suggestions for future research specific to needs of
      rural adolescents.

PMID- 9282049
TI  - The experience of the family of children with chronic illness at home in China.
AB  - The increasing prevalence of the nuclear family in China challenges the cultural
      ideal and tradition of the extended family caring for children with chronic
      illness at home. This study examined and documented the caregiving experiences in
      a sample of this population of children and their families. A descriptive survey
      with both quantitative and qualitative questions was developed and used to
      interview a total of 75 families in three urban areas of China. Factors such as
      the severity of illness, physical symptoms, the amount of assistance the child
      needed for daily living, and the emotional and social impact on the child were
      identified. Descriptions of the family's living circumstances, caregiving
      situations, and the child's experiences are illustrated through the use of three
      case studies.

PMID- 9282051
TI  - Organization and development of a pediatric end stage renal disease teaching
      protocol for peritoneal dialysis.
AB  - Peritoneal dialysis is one of the treatments for end stage renal disease that
      requires considerable expertise. When neonates or children develop end stage
      renal disease, both the patient and family members must be provided with
      substantial education and training. The organization of education and training is
      paramount, especially as length of stay is limited with managed care. The
      development of an organized interdisciplinary approach for this instruction and
      pediatric patient teaching protocol for management of home peritoneal dialysis
      therapy is discussed in this article. The protocol provides learning content,
      methodologies and patient/family outcomes and is accompanied by a documentation
      tool that serves as communication for directing team member reinforcement of
      content until outcomes are met. Since completion of the protocol, eight pediatric
      patients have been placed on this teaching plan with extremely positive outcomes.

PMID- 9282052
TI  - Family Voices: building voices for our children with special health care needs.
AB  - Family Voices is a national grassroots clearing-house for information and
      education concerning the health care of children with special health needs.
      Through the collective efforts of volunteer Coordinators in each state, 10
      Regional Coordinators, and a small staff, Family Voices keeps aware of and
      involved in public and private sector health care changes that affect children
      and families. Family Voices, over 10,000 members strong, works in partnership
      with health care providers in public and private hospitals, public health
      programs, in state capitals, and Washington, DC to bring the family perspective
      to policy discussions and decisions. Pediatric nurses are invited to work in
      partnership with Family Voices to advocate for children and families.

PMID- 9282053
TI  - Pediatric management problems. Kawasaki disease.

PMID- 9282054
TI  - ASPEN recommendations to conserve intravenous multivitamins in United States.

PMID- 9282055
TI  - Effect of kangaroo care on sleep time for neonates.
AB  - PURPOSE: To determine the change in behavioral state and physiologic parameters
      due to Kangaroo Care (K Care). METHOD: A quasi-experimental design using a
      pretest-posttest with neonates serving as their own controls for 4 episodes of 1
      hour each: Pre K Care, K Care and Post K Care. Twenty neonate-parent dyads
      participated. RespiTrace PT Non-invasive Monitoring system was used to record
      heart and respiratory rate and oxygen saturation. Behavioral state was derived
      from analyzing RespiTrace PT cardiorespiratory data as well as observation
      criteria. FINDINGS: There was a significant increase in sleep time for the
      neonates during K Care as compared to when they were not receiving K Care. The
      neonates exhibited less agitation, apnea, and bradycardia episodes and maintained
      stable oxygen saturation during K Care. CONCLUSION: K Care is safe even for very
      small neonates and is well tolerated. The stability of the preterm infants
      receiving K Care documents the need to incorporate it into standards of care.

PMID- 9282056
TI  - Dilemmas facing nurses who care for Munchausen syndrome by Proxy patients.
AB  - Diagnostic practices, including video surveillance, in Munchausen Syndrome by
      Proxy can lead to multiple nursing dilemmas. A case study with discussion of
      these dilemmas and suggestions to deal with them is presented to help nurses cope
      more effectively with this difficult diagnosis.

PMID- 9282058
TI  - Cast changes: synthetic versus plaster.
AB  - A review of the changes in casting since the introduction of improved synthetic
      casting materials in the 1970s is presented. There is very little in the
      literature on nursing implications regarding the newer casting materials.
      Improvements in synthetic materials used in the casting of children include a
      fiberglass-free, latex-free casting polymer, with child-friendly prints now
      available. Though the use of synthetic casting predominates the market, plaster
      of Paris is still the mainstay for serial casting and casting requiring superior
      moldability and conformability. The advantages and disadvantages of synthetic and
      plaster of Paris casting, as well as nursing care of the child in each type of
      cast are summarized.

PMID- 9282059
TI  - State legislatures expand children's health coverage.

PMID- 9282060
TI  - Article on UTIs provided key assessment and diagnosis information.

PMID- 9282062
TI  - The opportunities and challenges of geriatric rehabilitation--a success story.
AB  - The rehabilitation philosophy of promoting function and independence should be
      the backbone of gerontological nursing practice. The attitudes and skills of
      nurses determine the rehabilitation climate for geriatric patients. Nurses need
      to be aware of the principles of geriatric rehabilitation nursing. The Geriatric
      Rehabilitation Program at Joseph Brant Memorial Hospital has not only
      acknowledged and enhanced the knowledge and skills of nursing staff, but has also
      raised awareness that geriatric rehabilitation is possible. It has also provided
      a structure in which nurses can practise geriatric rehabilitation nursing. Mrs.
      C. is a wonderful example of what this kind of program can do for patients. The
      face of rehabilitation nursing is changing, and it is time to turn the challenges
      of geriatric rehabilitation into opportunities for our patients, their families,
      and ourselves.

PMID- 9282061
TI  - Attitudes training issues and barriers for community nurses implementing an
      advance directive program.

PMID- 9282063
TI  - Foot care clinics and primary health care.

PMID- 9282064
TI  - A qualitative study to determine the impact of caregiver education and support
      groups.

PMID- 9282065
TI  - Excellence in respiratory nursing practice: exemplars and commentaries.

PMID- 9282066
TI  - RNS president's message.

PMID- 9282067
TI  - Comparison of nurses' and patients' perceptions about patients' functional levels
      after discharge.

PMID- 9282068
TI  - Advances in the respiratory system treatment of cystic fibrosis.

PMID- 9282069
TI  - Sexual harassment.

PMID- 9282070
TI  - Nursing career structure. Nursing practice coordinator.

PMID- 9282071
TI  - WorkCover Queensland Act 1996.

PMID- 9282072
TI  - Issues of recruitment and retention.

PMID- 9282073
TI  - Health (drugs and poisons) regulation 1996. The implications for nurses.

PMID- 9282074
TI  - [Poisoning from spider bites. How to treat].
AB  - Three types of poisonous spiders that inhabit the Iberian Peninsula are
      discussed. How to identify these spiders and the type of venom they inject are
      described. Symptoms and specific treatments, both in the field and in the
      hospital, are listed.

PMID- 9282075
TI  - [Insulin combinations: improving the treatment of juvenile diabetes].
AB  - In order to establish some general insulin therapy norms, a study was performed
      on a group of 77 young diabetics (average age 11.7) over the course of a 14 day
      stay at a summer camp. The children were placed on an appropriate diabetic diet
      and received twice daily insulin injections. 83.1% of the group (N = 64) ended up
      using a mixture of Regular and NPH insulin while the other 16.9% used only NPH
      insulin. Daily, two-thirds of the total dosage was given before breakfast (63.4
      +/- 9.6%) and the other one-third (36.6 +/- 9.6%) was given before dinner. The
      proportion of mixed insulins were the following: before breakfast 10.3 +/- 6.6%
      Regular, 89.7 +/- 6.6% NPH; before dinner 12.5 +/- 7.3% Regular, 87.5 +/- 7.3%
      NPH, 14.9% of the blood glucose tests showed hypoglycemia. The majority of these
      results were after some physical activity (37.8% before breakfast, 20.7% before
      dinner) and a few (18.3%) become so at night. Thus, this work reflects the
      importance of proportion and regularity of insulin use, as well as the need for
      bedtime blood glucose levels in children with diabetes.

PMID- 9282076
TI  - [Standardizing care. When the intervention is valid].
AB  - The objectives of this study were: A) to assemble a Standard Care Plan Guide
      taken from both nursing care records as well as data from a bibliography review;
      B) to know the number of nursing interventions and evaluate their suitability
      according to the stated nursing diagnosis. These results can then be compared
      before and after using the Standard Care Plan Guide. An analysis of 1827 nursing
      care records was performed. The first phase, after studying 1255 records,
      consisted of standardizing the care to correspond with 36 nursing diagnoses
      previously selected from the NANDA taxonomy. The second phase saw the standard
      care practice incorporated by the nursing staff. And finally, a comparison was
      made of the results between phase one and three (before and after the
      incorporation of the Standard Care Plan Guide.) The number of nursing
      interventions notably increased, jumping from 3263 in the first phase up to 4271
      in the third. The average nursing action per patient rose from 3.03 to 9.09.
      Also, the diagnostic categories increased, going from 930 in the first phase up
      to 1624 in the third. The average number of correctly stated diagnoses per
      patient climbed from 1.56 to 2.78. The authors state that better nursing care and
      attention to the patient can occur if the nurses are given the conceptual
      instruments and training that will facilitate their daily tasks.

PMID- 9282079
TI  - [Urinary incontinence in a unit of a medium to large facility. Clinical and
      nursing implications].

PMID- 9282078
TI  - [Another year of the Ausonia Prize for Incontinence Nursing. The awards landed in
      the cities of San Sebastian and Barcelona].

PMID- 9282080
TI  - [Urinary incontinence and travel in the elderly].

PMID- 9282081
TI  - [A basic health care center. Care oriented at the community].
AB  - Principle problems of a basic health care area (Lerida) are identified. This
      area, which has a patient case load of 22,244 people, was studied during the
      winter of 1993-94 by using information from various sources. Results indicate
      that the population of this community are basically young, urban, have a high
      cultural and social level, and are mostly employed. The principle causes of
      mortality are the same as in the rest of Cataluna. Diseases that cause the most
      working days lost to illness are: respiratory, mental and bone-joint problems.
      The most frequent diseases seen in the clinic are: hypertension, respiratory
      infections, endocrine and mental. An overall look at the state of health of these
      patients show that the principle problems are: tobacco use, high blood pressure,
      arthritis, lumbago, depression, stroke, diabetes and breast cancer.

PMID- 9282083
TI  - [Amputation of a lower extremity. Nursing care].
AB  - Explored here are the types of nursing interventions that have been used for
      patients with lower limb amputations. A general discussion of why amputations are
      performed, as well as types and levels, is presented. The phases of pre-op., post
      op., and discharge are explained, with special emphasis on patient positioning
      and prosthesis care.

PMID- 9282082
TI  - [Breast-feeding].
AB  - In order to promote maternal lactation it is necessary to know what problems
      prevent it. With this in mind, a survey of 202 mothers who had children between
      the first of October and the end of November in 1992 was conducted. 91.5% of
      these mothers began normal lactation, yet 30.7% were incapable of giving milk
      after one month. A high frequency of lactating failure correlated with women from
      disadvantaged income groups. Factors that influenced the duration and difficulty
      of breast feeding were: lactating problems with the previous child, family
      opinions, rigid feeding schedules, excessive maternal preoccupation, working out
      of the home. Once the problems were recognized, a second objective of this study
      was to design a plan that would create positive attitudes toward maintaining
      natural lactation. After putting this plan to work, a three month study showed
      that 70.2% of the mothers in a experimental group continued to breast feed,
      whereas only 39.5% of the control group did. After four months 55% of the
      variable group was still nursing their children, while the control group fell to
      30.2%.

PMID- 9282084
TI  - [Teacher education. Experience at Argentina University].

PMID- 9282085
TI  - [Fear to speak in public or fear of place].

PMID- 9282086
TI  - [Percutaneous surgery for renal calculi].

PMID- 9282087
TI  - [Extracorporeal lithotripsy].

PMID- 9282088
TI  - [The mobile lithotripsy unit].

PMID- 9282089
TI  - [The emergency cart].

PMID- 9282090
TI  - [Testing outside of the laboratory: stakes and perspectives].

PMID- 9282091
TI  - [Anesthesia in urology. General review].

PMID- 9282092
TI  - [Care at the end of life].

PMID- 9282093
TI  - [Emergencies in psychiatry and in geriatric psychiatry].

PMID- 9282094
TI  - [Geronto-psychiatric emergencies].

PMID- 9282095
TI  - [Emergencies in a geriatric-psychiatric day hospital].

PMID- 9282096
TI  - [Emergencies, crisis and geriatric psychiatric hospitalization].

PMID- 9282097
TI  - [Emergencies in a general hospital. Acute psychiatric problems in the elderly].

PMID- 9282098
TI  - [General psychiatric services. Response to emergencies in the aged].

PMID- 9282099
TI  - [Emergencies and the elderly. Short loss of consciousness].

PMID- 9282100
TI  - [Knowing more in order to help. Thyroid disorders in the elderly].

PMID- 9282101
TI  - [Dietetics. Evaluation of the nutritional status].

PMID- 9282102
TI  - [Relations between nurses, families and the elderly].

PMID- 9282103
TI  - [Comfort and quality of care. Hydrating a dependent patient. Analyzing your daily
      practice].

PMID- 9282104
TI  - [Facilitating communication for the elderly. Small useful gadgets].

PMID- 9282105
TI  - [The disability identification card].

PMID- 9282106
TI  - [Volunteers in a residence for the aged].

PMID- 9282107
TI  - [Architecture. HOTELIA, an innovative concept].

PMID- 9282108
TI  - The biology of replicative senescence.
AB  - Most cells cannot divide indefinitely due to a process termed cellular or
      replicative senescence. Replicative senescence appears to be a fundamental
      feature of somatic cells, with the exception of most tumour cells and possibly
      certain stem cells. How do cells sense the number of divisions they have
      completed? Although it has not yet been critically tested, the telomere
      shortening hypothesis is currently perhaps the best explanation for a cell
      division 'counting' mechanism. Why do cells irreversibly cease proliferation
      after completing a finite number of divisions? It is now known that replicative
      senescence alters the expression of a few crucial growth-regulatory genes. It is
      not known how these changes in growth-regulatory gene expression are related to
      telomere shortening in higher eukaryotes. However, lower eukaryotes have provided
      several plausible mechanisms. Finally, what are the physiological consequences of
      replicative senescence? Several lines of evidence suggest that, at least in human
      cells, replicative senescence is a powerful tumour suppressive mechanism. There
      is also indirect evidence that replicative senescence contributes to ageing.
      Taken together, current findings suggest that, at least in mammals, replicative
      senescence may have evolved to curtail tumorigenesis, but may also have the
      unselected effect of contributing to age-related pathologies, including cancer.

PMID- 9282109
TI  - Multiple pathways to cellular senescence: role of telomerase repressors.
AB  - Telomeres progressively shorten with age in somatic cells in culture and in vivo
      because DNA replication results in the loss of sequences at the 5' ends of double
      stranded DNA. Whereas somatic cells do not express the enzyme, telomerase, which
      adds repeated telomere sequences to chromosome ends, telomerase activity is
      detected in immortalised and tumour cells in vitro and in primary tumour tissues.
      This represents an important difference between normal cells and cancer cells,
      suggesting that telomere shortening causes cellular senescence. Hybrids between
      immortal cells and normal cells senesce, indicating that immortal cells have
      lost, mutated or inactivated genes that are required for the programme of
      senescence in normal cells. Genes involved in the senescence programme have been
      mapped to over ten different genetic loci using microcell fusion to introduce
      human chromosomes and restore the senescence programme. Multiple pathways of
      cellular senescence have also been demonstrated by chromosome transfer,
      indicating that the functions of the mapped senescence genes are probably
      different. One possibility is that one or more of these senescence genes may
      suppress telomerase activity in immortal cells, resulting in telomere shortening
      and cellular senescence. To test this hypothesis, telomerase activity and the
      length of terminal restriction fragments (TRFs) have been examined in microcell
      hybrids. Re-introduction of a normal chromosome 3 into the renal cell carcinoma
      cell line RCC23, which has the short arm of chromosome 3, restored cellular
      senescence. The loss of indefinite growth potential was associated with the loss
      of telomerase activity and shortening of telomeres in the RCC cells containing
      the introduced chromosome 3. However, microcell hybrids that escaped from
      senescence and microcell hybrids with an introduced chromosome 7 or 11 maintained
      telomere lengths and telomerase activity similar to the parental RCC23. Thus,
      restoration of cellular senescence by chromosome 3 is associated with repression
      of telomerase function in RCC cells. This evidence suggests that telomerase
      suppression is one of several pathways involved in immortalisation.

PMID- 9282110
TI  - Proliferative lifespan checkpoints: cell-type specificity and influence on tumour
      biology.
AB  - Lifespan checkpoints are viewed here as intrinsic mechanisms which desensitise
      cells to external growth signals as a programmed response to proliferative age,
      as distinct from externally-triggered differentiation. This review focuses on the
      role of tumour suppressor gene products as essential mediators of cell cycle
      arrest at lifespan checkpoints, concentrating in particular on p53. Although
      drawing inevitably on fibroblast senescence and telomere erosion paradigms, other
      lifespan clocks and signal pathways are discussed. Particular emphasis is placed
      on cell-type diversity in the nature, number and timing of lifespan checkpoints
      and its importance for tumour biology. Breast and thyroid cancer are used to
      illustrate the concept that the "choice" of checkpoint(s) in a given normal cell
      may have a determining influence on the mutational spectrum and clinical
      behaviour of its tumours.

PMID- 9282112
TI  - The DNA structures at the ends of eukaryotic chromosomes.
AB  - The sequence organisation of the telomeric regions is extremely similar for all
      eukaryotes examined to date. Subtelomeric areas may contain large sequence arrays
      of middle repetitive, complex elements that sometimes have similarities to
      retrotransposons. In between and within these complex sequences are short,
      satellite-like repeats. These areas contain very few genes and are thought to be
      organised into a heterochromatin-like domain. The terminal regions almost
      invariably consist of short, direct repeats. These repeats usually contain
      clusters of 2-4 G residues and the strand that contains these clusters (the G
      strand) always forms the extreme 3'-end of the chromosome. Thus, most telomeric
      repeats are clearly related to each other which in turn suggests a common
      evolutionary origin. A number of different structures can be formed by single
      stranded telomeric G strand repeats and, as has been suggested recently, by the G
      strand. Since the main mechanism for the maintenance of telomeric repeats
      predicts the occurrence of single-stranded extensions of the G strand, the
      propensity of G-rich DNA to fold into alternative DNA structures may have
      implications for telomere biology.

PMID- 9282113
TI  - The implications of telomerase biochemistry for human disease.
AB  - The replication of linear chromosome termini (telomeres) cannot be completely
      replicated by conventional DNA polymerases. Telomerase is a special DNA
      polymerase used by most eukaryotes to solve the telomere and replication problem.
      Telomerase is necessary for indefinite cell division in most immortal cells, but
      apparently unnecessary for the normal function of most somatic tissues.
      Telomerase may play a critical role in some genetic diseases, in regulating the
      lifespan of normal cells, and in tumorigenesis. This article reviews the
      structure and reaction mechanism of mammalian telomerase and how it may be
      exploited to control some human diseases.

PMID- 9282111
TI  - The genetic basis of human keratinocyte immortalisation in squamous cell
      carcinoma development: the role of telomerase reactivation.
AB  - Normal human keratinocytes have a finite replicative lifespan which culminates in
      senescence. Chromosomal telomere length may act as a mediator of replicative
      senescence, signalling cell cycle arrest in G1 when one or more telomeres become
      too short. Telomeric attrition in normal keratinocytes may be due to inadequate
      levels of telomerase activity and possibly also to oxidative damage. In advanced
      squamous cell carcinoma replicative senescence breaks down to yield immortal
      variants, in which several dominantly acting genes are functionally compromised,
      including p53 and the cyclin D-Cdk4/6 inhibitor CDKN2A/p16. The increased
      activity of both of these proteins would be expected to contribute to the G1
      arrest in senescence and we have shown that levels of p16 are dramatically
      increased in senescent keratinocytes. In addition, two other genes which control
      a cell cycle G1 checkpoint independently of p53 and pRb appear dysfunctional.
      These genes are uncloned but map to chromosome 4q and 7q31.1 and appear to
      represent senescence complementation groups B and D, respectively. In immortal
      neoplastic keratinocytes, telomerase is strongly upregulated and there is
      evidence for a suppressor of the enzyme on the short arm of chromosome 3 mapping
      to 3p21.2-p21.3. We have also mapped the human telomerase RNA gene to 3q26.3 and
      found it to be overrepresented or amplified in a proportion of squamous cell
      tumours and cell lines. These observations may explain why isochromosome 3q is so
      common in human squamous carcinoma. None of these genetic alterations are seen in
      carcinomas which senesce and suggest that multiple genetic alterations are
      required for keratinocyte immortality.

PMID- 9282115
TI  - Telomere dynamics and telomerase activity in in vitro immortalised human cells.
AB  - This article reviews the current understanding of the involvement of telomerase
      in in vitro immortalisation of human cells. In vitro immortalisation with DNA
      tumour viruses or chemicals usually occurs in two phases. The first stage is an
      extension of lifespan beyond that at which cells would normally senescence, after
      which the culture enters a period of crisis. The second stage involves the escape
      from crisis of a rare cell in the culture, which goes on to proliferate
      indefinitely. The hypothesis that telomere shortening acts as a signal for
      senescence and crisis, and that cells need to activate telomerase to survive
      these states, gained support from early studies examining telomere behaviour and
      telomerase activity in immortalised cell lines. In many cases, telomeres were
      found to continue to shorten during the phase of extended lifespan, and no
      telomerase was detectable. Cells which survived crisis had activated telomerase
      and had stable or lengthened telomerase. However, it is now clear that this model
      does not apply to all cell lines. Approximately a quarter of in vitro
      immortalised cell lines so far examined have no detectable telomerase activity,
      yet have very long and heterogeneous telomeres. These cell lines have acquired a
      novel mechanism for lengthening their telomeres, named ALT (Alternative
      Lengthening of Telomeres). The nature of ALT is not yet understood, but may
      involve non-reciprocal recombination between telomeres. ALT is not merely a
      phenomenon of in vitro immortalised cell lines, but has also been found in
      tumours and tumour-derived cell lines. Furthermore, there are a number of cell
      lines which have been shown to have low levels of telomerase prior to crisis
      while telomere shortening is still occurring, and the function of these low
      levels of telomerase activity is unknown.

PMID- 9282114
TI  - Multiple pathways for the regulation of telomerase activity.
AB  - The ends of vertebrate chromosome are composed of large tracts of a repeated
      sequence, TTAGGG, which are known as telomeres. Normal somatic cells
      progressively lose telomeric repeats with each successive cell division due to
      incomplete replication. Immortal and cancer cells compensate for telomeric loss
      by expressing the enzyme telomerase, an RNA-dependent DNA polymerase that
      maintains telomere length. Telomerase activity has been detected in almost 90% of
      all human cancers. Telomerase activity is generally absent in normal somatic
      tissues but is detected in adult testes, activated lymphocytes, and lower levels
      are expressed in proliferative cells of renewal tissues. Telomerase activity is
      downregulated in cells that exit the cell cycle via either terminal
      differentiation or (reversible) quiescence. Inhibition of telomerase activity in
      tumour cells may provide an effective way to treat cancer by potentially reducing
      the recurrence of tumours due to occult micro-metastases. An understanding of the
      pathways involved in telomerase regulation will be important for determining the
      most practical means of inhibiting its activity.

PMID- 9282116
TI  - Telomeres and telomerase in normal and malignant haematopoietic cells.
AB  - The normal haematopoietic system harbours telomerase-competent cells with a
      capacity to upregulate the activity to notable levels in a telomere length
      independent manner. Strong telomerase activity is found in progenitor stem cells
      and activated lymphocytes in vitro as well as in vivo, indicating that cells with
      high growth requirements can readily upregulate telomerase. Despite detection of
      telomerase activity, a gradual telomere erosion occurs in stem cells and
      lymphocytes, with significantly shortened telomeres at higher ages, a phenomenon
      that might be of importance for developing immunosenescence and exhausted
      haematopoiesis. In malignant haematopoietic disorders telomerase activity is a
      general finding with large differences in activity levels. The strongest
      telomerase expression has been shown in acute leukaemias and non-Hodgkin's
      lymphomas, especially high grade cases. There are indications that the level of
      activity might parallel tumour progression and be of prognostic relevance, but
      studies of larger patient materials are needed. An association between the cell
      cycle and telomerase activity exists, especially for normal haematopoietic cells,
      and induction of a differentiation programme in immortalised cell lines
      downregulates telomerase activity. The expression of telomerase activity seems to
      be regulated at different levels, since for immature bone marrow cells the level
      of activity seemed to parallel better the phenotype than the proliferation state.
      The frequent expression of telomerase in leukaemias and lymphomas makes these
      disorders interesting targets for future anti-telomerase therapy.

PMID- 9282117
TI  - Clinical implications of telomerase in cancer.
AB  - Cellular immortality is believed to be a critical step in tumorigenesis. As an
      important component of the telomere maintenance mechanism, the activation of the
      enzyme telomerase is tightly associated with cellular immortality and cancer.
      Telomerase expression is detected in a majority of tumours, but is absent in most
      somatic tissues and correlates to clinical outcome in a number of cancer types.
      Telomerase expression is associated with the stage of differentiation but not
      necessarily with the rate of cell proliferation. Data also indicate that
      inhibition or absence of telomerase may result in cell crisis in cancer cells and
      tumour regression in cancer patients. These results suggest that cancer therapy
      based on telomerase inhibition could be a more effective and safer treatment for
      cancer, as well as provide a more accurate means for diagnosing and predicting
      clinical outcome in cancer. Complete understanding of the role of telomerase in
      tumorigenesis through well-designed clinical studies will have a significant
      clinical impact on the treatment and diagnosis of cancer.

PMID- 9282118
TI  - A survey of telomerase activity in human cancer.
AB  - Research on the association of the ribonucleoprotein enzyme, telomerase, with
      human cancer has expanded rapidly in recent years. Essentially all major types of
      cancer have been screened and the presence of telomerase activity has been
      detected in the vast majority of cases. In this article we provide a summary, in
      table form, of the current data.

PMID- 9282119
TI  - Telomere structure and telomerase expression during mouse development and
      tumorigenesis.
AB  - Mouse telomeres are on average longer than those of man, raising questions
      regarding the link between telomere loss and replicative senescence in mice and
      the requirement for telomerase activity for mouse cell immortalisation. However,
      the emerging data on telomerase activity during tumorigenesis in the mouse must
      be interpreted in the context of the very different structure of mouse telomeres.
      It will be argued here that the evidence for a casual link between telomere loss
      and replicative senescence is weak in the mouse, with the observed upregulation
      of telomerase activity in mouse tumours perhaps instead reflecting co-ordinated
      regulatory changes in tumour cells. Its absence would be consistent with
      evolutionary considerations, which hypothesise that such a link is an additional
      layer of control against tumour formation that has evolved in man. The very
      different genomic substrates for telomerase in humans and mice mean that the
      initial phenotype of a telomerase knock-out mouse does not necessarily critically
      address the existence of a link between telomerase and tumorigenesis in man.

PMID- 9282120
TI  - Lung function testing: methods and reference values for forced expiratory volume
      (FEV1) and transfer factor (TL).

PMID- 9282121
TI  - Occupational exposure to dust: inflammation and ischaemic heart disease.
AB  - OBJECTIVES: To review the possible association between occupational exposure to
      dust and ischaemic heart disease (IHD). METHODS: A literature search was
      performed of relevant studies regarding IHD in specific exposures to dust. The
      chosen exposures were arsenic, asbestos, beryllium, lead, polycyclic aromatic
      hydrocarbons, and quartz. The chosen occupations were farmers, paper and paper
      pulp workers, sawyers, and welders. DISCUSSION: A theory was launched in 1995
      that urban particulate air pollution may provoke alveolar inflammation, with
      release of mediators capable of increasing blood coagulability in susceptible
      people and cause cardiovascular deaths. The present review expands this
      hypothesis and links occupational exposure to inhaled particles with the
      occurrence of ischaemic heart disease. CONCLUSION: This hypothesis should be
      tested by comparing the concentrations of fibrinogen in workers exposed and
      nonexposed to particles with control for other possible confounders such as
      smoking habits.

PMID- 9282122
TI  - Mortality of workers exposed to methylene chloride employed at a plant producing
      cellulose triacetate film base.
AB  - OBJECTIVE: To study mortality among 1785 employees of a factory that produced
      cellulose triacetate film base at Brantham in the United Kingdom. Also, to
      investigate patterns of mortality after exposure to methylene chloride; in
      particular, mortality from liver and biliary tract cancer, lung cancer,
      pancreatic cancer, and cardiovascular disease. SUBJECTS AND METHODS: All male
      employees with a record of employment at the film factory in 1946-88. A total of
      1473 subjects worked in jobs that entailed exposure to methylene chloride. The
      mean duration of exposure was nine years at 19 ppm (eight hour time weighted
      average). RESULTS: In the cohort, 334 deaths were identified up to 31 December
      1994. Mortalities for the cohort were compared with national and local rates and
      expressed as standardised mortality ratios (SMR). In the subcohort of workers
      exposed to methylene chloride, substantially reduced mortalities compared with
      national and local rates were found for all causes, all cancers, and the
      principal cancer sites of interest. The significantly reduced lung cancer
      mortalities in exposed workers (SMR 48) seemed to reflect the restrictions on
      smoking at the workplace. In contrast, mortality from ischaemic heart disease in
      exposed workers, although lower than national rates (SMR 92), was slightly
      increased compared with local rates. However, mortality from ischaemic heart
      disease was lower in active employees (SMR 83) where a direct effect of exposure
      to methylene chloride should be concentrated. No in service mortality due to
      ischaemic heart disease was found in workers with the highest cumulative exposure
      (> or = 800 ppm-years). CONCLUSIONS: The study provided no indication that
      employment at the plant, or exposure to methylene chloride, had adversely
      affected the mortalities of workers.

PMID- 9282123
TI  - Laryngeal and hypopharyngeal cancer and occupation: results of a case control
      study.
AB  - OBJECTIVES: To ascertain whether certain occupations are associated with
      laryngeal or hypopharyngeal cancer. METHODS: A hospital based case-control study
      was carried out in 15 hospitals in France. It included 528 male cases diagnosed
      between January 1989 and April 1991, and 305 male controls with various other
      types of cancer. Interviews were carried out to obtain lifetime job histories and
      information on potential confounders. Logistic regression was used to compute the
      odds ratios (OR) for each of about 80 occupations and industries. RESULTS: There
      was an excess risk of laryngeal and hypopharyngeal cancer among service workers
      (OR 2.2, 95% confidence interval (95% CI) 1.3 to 3.9), agricultural and animal
      husbandry workers (OR 1.6, 95% CI 0.9 to 2.8), miners and quarrymen (OR 2.0, 95%
      CI 0.9 to 4.3), plumbers and pipe fitters (OR 2.6, 95% CI 0.8 to 8.1), glass
      formers and potters (OR 4.3, 95% CI 1.0 to 18) transport equipment operators (OR
      1.5, 95% CI 1.0 to 2.5), and unskilled workers (OR 1.7, 95% CI 1.0 to 2.9).
      Analysis by industrial branch showed an excess risk for coal mining (OR 2.1, 95%
      CI 1.1 to 4.1), manufacture of metal products (OR 1.9, 95% CI 1.0 to 3.3), and
      administration and sanitary services (OR 1.7, 95% CI 1.1 to 2.5). CONCLUSION:
      These results suggest that occupational exposure might have a role in generating
      laryngeal and hypopharyngeal cancer, and indicate the need for further evaluation
      of these findings, an for the identification of the carcinogens which might
      account for the excess risks found for certain occupations.

PMID- 9282124
TI  - Contrast sensitivity measurement in evaluations of visual symptoms caused by
      exposure to triethylamine.
AB  - OBJECTIVES: To determine whether blurred vision caused by exposure to
      triethylamine (TEA) can be detected by the measurement of contrast sensitivity.
      METHODS: 41 cold box core makers of three foundries and 82 control workers were
      examined. A detailed ocular and medical history was obtained from the subjects.
      The contrast sensitivity of the core makers was measured on Monday and Friday of
      the same week both before and immediately after work and also on a third day,
      when air samples of TEA were collected. Contrast sensitivity and visual acuity
      were measured by optotype figures at full contrast, 2.5% contrast, and 0.6%
      contrast. The changes in contrast sensitivity were used for the analysis. The
      results of binocular vision and the results of the dominant eye were analysed.
      Urine specimens for the analysis of TEA were collected on every occasion when
      contrast sensitivity was measured. RESULTS: 78% of the core makers had had
      symptoms of blurred vision, and 31% had had trouble driving or working. The
      breathing zone eight hour time weighted average TEA concentrations were 0.3-60
      mg/m3. The mean urinary TEA concentration after the shift was 35 mmol/mol
      creatinine. Continuous monitoring showed high peaks of TEA leakage at a core
      making machine. Changes in binocular visual acuity did not differ between the
      exposed and unexposed workers. The contrast sensitivity decreased in 49% of the
      core makers and 21% of the controls (P = 0.002). CONCLUSIONS: The blurred vision
      caused by exposure to TEA can be documented by measuring contrast sensitivity.
      The mechanism by which TEA produces symptoms remains an issue of further study.

PMID- 9282125
TI  - Effects of low level exposure to lead on neurophysiological functions among lead
      battery workers.
AB  - OBJECTIVES: Assessment of neurophysiological functions in workers with low level
      exposure to lead and evaluation of the efficacy of bone lead measurements in the
      prediction of effects of lead. METHODS: Exposure to lead of 60 workers from a
      lead battery battery factory was estimated from historical blood lead
      measurements and analysis of lead in the tibial and calcaneal bones with x ray
      fluorescence. Peripheral and central nervous system functions were assessed by
      measuring conduction velocities, sensory distal latencies, sensory amplitudes,
      and vibration thresholds as well as by quantitative measurement of the absolute
      and relative powers and mean frequencies of different electroencephalograph (EEG)
      channels. RESULTS: Sensory amplitudes, and to a smaller degree sensory or motor
      conduction velocities, showed a negative correlation with long term exposure to
      lead, most clearly with integrated blood lead concentration and exposure time.
      Vibration thresholds measured in the arm were related to recent exposure to lead,
      those measured in the leg to long term exposure. The alpha and beta activities of
      the EEG were more abundant in subjects with higher long term exposure to lead.
      Calcaneal lead content reflected short term exposure, tibial lead content
      reflected long term exposure. Blood lead history showed a closer relation with
      effects of lead than the tibial or calcaneal lead concentrations. CONCLUSIONS:
      Vibratory thresholds, quantitative EEG, and to a smaller extent the sensory
      amplitude, provide sensitive measures of effects of lead in occupationally
      exposed adults. Most accurate estimates of health risks induced by lead can be
      obtained from a good history of blood lead measurements. If such a history of
      blood lead concentrations is not available, analysis of bone lead may be used for
      the assessment of health risks.

PMID- 9282127
TI  - Medical insurance claims associated with international business travel.
AB  - OBJECTIVES: Preliminary investigations of whether 10,884 staff and consultants of
      the World Bank experience disease due to work related travel. Medical insurance
      claims filed by 4738 travellers during 1993 were compared with claims of non
      travellers. METHODS: Specific diagnoses obtained from claims were analysed
      overall (one or more v no missions) and by frequency of international mission (1,
      2-3, or > or = 4). Standardised rate of claims ratios (SSRs) for each diagnostic
      category were obtained by dividing the age adjusted rate of claims for travellers
      by the age adjusted rate of claims for non-travellers, and were calculated for
      men and women travellers separately. RESULTS: Overall, rates of insurance claims
      were 80% higher for men and 18% higher for women travellers than their non
      travelling counterparts. Several associations with frequency of travel were
      found. SRRs for infectious disease were 1.28, 1.54, and 1.97 among men who had
      completed one, two or three, and four or more missions, and 1.16, 1.28, and 1.61,
      respectively, among women. The greatest excess related to travel was found for
      psychological disorders. For men SRRs were 2.11, 3.13, and 3.06 and for women,
      SRRs were 1.47, 1.96, and 2.59. CONCLUSIONS: International business travel may
      pose health risks beyond exposure to infectious diseases. Because travellers file
      medical claims at a greater rate than non-travellers, and for many categories of
      disease, the rate of claims increases with frequency of travel. The reasons for
      higher rates of claims among travellers are not well understood. Additional
      research on psychosocial factors, health practices, time zones crossed, and
      temporal relation between travel and onset of disease is planned.

PMID- 9282126
TI  - No increased DNA damage in peripheral lymphocytes of sewage workers as evaluated
      by alkaline single cell gel electrophoresis.
AB  - OBJECTIVES: To study whether sewage workers are exposed to genotoxic substances.
      An increased risk of cancers among sewage workers has been noted. If this
      increased risk is due to an exposure to genotoxic agents, primarily DNA damage
      could be used as a biological marker of exposure. METHODS: In a cross sectional
      study, DNA damage in peripheral lymphocytes from 35 sewage workers and 30
      controls was compared with alkaline single cell gel electrophoresis, a technique
      for detecting single strand breaks and alkali labile sites in DNA. The controls
      were selected from among municipal workers matched for age and smoking habit.
      Information about occupational exposures and possible confounders was collected
      by means of a questionnaire. RESULTS: No increase in DNA damage was found among
      the sewage workers when compared with the unexposed controls. CONCLUSIONS: The
      failure to detect increased damage to DNA in peripheral lymphocytes by alkaline
      single cell gel electrophoresis suggests that the sewage workers studied here
      were not exposed to genotoxic agents to a greater extent than other municipal
      workers. It may be, however, that the lymphocyte is not the appropriate target
      cell to study, or that sewage workers are exposed to carcinogens which do not
      damage the genetic material.

PMID- 9282128
TI  - Priorities in occupational health research: a Delphi study in The Netherlands.
AB  - OBJECTIVES: To achieve a coherent programme of topics for research in
      occupational health and safety, with well founded priorities and to relate them
      to perceived gaps and needs in The Netherlands. METHODS: In the first phase of
      the study 33 key informants were interviewed. In the second phase questionnaires
      were sent to 150 Dutch experts (including the key informants). Four groups were
      recruited, originating from: occupational health and safety services; scientific
      research institutes; governmental and other administrative bodies; and companies.
      Using the Delphi technique, the experts were asked to prioritize several topics,
      which were placed under different headings. In the third phase five workshops
      were organised to elaborate on the highly prioritized topics. RESULTS: The
      response rates were 86% for the first and 81% for the second questionnaire. In
      the second round consistency was reached and consensus proved to be satisfactory;
      so that the Delphi process was stopped. There were surprisingly few differences
      in opinion between the four groups. The most important heading was
      "design/implementation/evaluation of measures", in which the topic cost-benefit
      analysis of measures had the highest score. "Assessment of relations between
      exposure and effect" was the second most important heading. Under this heading,
      topics on work stress were generally judged to be more important than topics on
      safety and biological, chemical, and physical hazards. The headings "occupational
      rehabilitation/sociomedical guidance" and "occupational health care/occupational
      health services" had about the sam priority, closely following the heading
      "assessment of relations between exposure and effect". CONCLUSIONS: The general
      agreement on priorities should provide a sufficiently broad basis for decision
      makers to initiate a long term programme for occupational health research and
      development in The Netherlands.

PMID- 9282130
TI  - Carpal tunnel syndrome: what is attributable to work? The Montreal study.
AB  - OBJECTIVE: To estimate the fraction of carpal tunnel syndrome (CTS) that is
      attributable to work in the total adult population of the island of Montreal.
      METHODS: The population consisted of 1.1 million people 20-64 years of age, with
      73.2% of men and 60.6% of women employed. The rates of first surgery for CTS were
      compared between occupational groups and the total adult population with the
      standardised incidence ratio (SIR) method. Rates of surgery for the island of
      Montreal were obtained from the provincial data base of payments. The
      occupational history was obtained from telephone interviews of a sample of
      surgical cases. The attributable fractions in exposed people were calculated with
      odds ratios (ORs) obtained from logistic regressions with non-manual workers as
      the control group. RESULTS: The surgical incidence of CTS was 0.9/1000 adults.
      SIRs for all manual workers were 1.9 (95% confidence interval (95% CI) 1.4-2.5)
      in men and 1.8 (95% CI 1.4-2.2) in women, and the fractions attributable to work
      were 76% (95% CI 47-88) and 55% (95% CI 33-69), respectively. Seven occupational
      groups were identified as having excess risk of surgical CTS, with fractions
      attributable to occupation ranging from 75% to 99%. CONCLUSION: Among manual
      workers on the island of Montreal, 55% of surgical CTS in women and 76% in men
      was attributable to work. Increased risk of surgical CTS was found in seven
      occupational groups.

PMID- 9282131
TI  - In vitro percutaneous penetration of methyl-parathion from a commercial
      formulation through the human skin.
AB  - OBJECTIVE: To compare in vitro percutaneous absorption of methyl-parathion
      dissolved in an acetone vehicle and in the form of a commercial formulation.
      METHODS: Penetration through the human skin was measured in Franz diffusion cells
      with full thickness skin from a human cadaver as the membrane. The two tailed non
      parametric Mann-Whitney U test was used to compare the cumulative diffusion of
      methyl-parathion in the receptor fluid of the cells at various time intervals.
      RESULTS: In vitro skin penetration of methyl-parathion was significantly higher
      with the commercial formulation. The percentage of the applied dose absorbed
      after 24 hours was 5.20% v 1.35%. The mean lag time was < 8 hours. CONCLUSION:
      Assessments of uptake and internal dose after exposure to pesticides should be
      based on the commercial products rather than active ingredients, because of the
      crucial role of the vehicle, as shown in this study.

PMID- 9282132
TI  - One program already offering managed care training.

PMID- 9282129
TI  - Risk of stillbirth from occupational and residential exposures.
AB  - OBJECTIVES: To analyse the risk of stillbirth from 12 residential and
      occupational maternal exposures during pregnancy. METHODS: Stillbirths and
      neonatal deaths in 1984 within 24 hours of birth from 10 California counties were
      identified from death certificates. Controls were randomly selected from live
      births born in 1984 and frequency matched to cases by maternal age and county.
      Data sources included vital statistics and a self-administered postal
      questionnaire. Logistic regression and proportional hazards modelling were
      performed; the proportional hazards considered the truncated opportunity for
      exposure among cases. Special focus was given to two cause of deaths groups:
      congenital anomalies (12% of deaths) and complications of the placenta, cord, and
      membranes (37% of deaths). RESULTS: Occupational exposure to pesticides during
      the first two months of gestation was positively associated with stillbirths due
      to congenital anomalies (odds ratio (OR) 2.4, 95% confidence interval (95% CI)
      1.0 to 5.9), and during the first and second trimesters with stillbirths due to
      all causes of death (risk ratios (RR) 1.3-1.4, 95% CI 1.0 to 1.7) and stillbirths
      due to complications of the placenta, cord, and membranes (RR 1.6-1.7, 95% CI 1.1
      to 2.3). Occupational exposure to video display terminals in the third trimester
      was found to have a modest inverse association with stillbirths (RR 0.7, 95% CI
      0.6, 0.9). Home pesticide exposure was positively associated with stillbirths due
      to congenital anomalies (OR 1.7, 95% CI 1.0 to 2.9). CONCLUSIONS: Occupational
      exposure to pesticides, especially during early pregnancy, had a clear positive
      association with stillbirths regardless of cause of death. Methodologically, this
      study of stillbirths is unique in its analysis of specific causes of death and
      use of time specific exposure windows.

PMID- 9282133
TI  - Debt and career choices of underrepresented minorities.

PMID- 9282134
TI  - Alleviating students' anxieties about PBL.

PMID- 9282135
TI  - Israel's unique approach to licensing immigrant physicians.

PMID- 9282136
TI  - Medical students' views on the teaching of immunology.

PMID- 9282137
TI  - Medical education and the needs of the public.

PMID- 9282138
TI  - Mechicare--a parable for the future.

PMID- 9282139
TI  - Florence Nightingale and medical statistics.

PMID- 9282140
TI  - A national survey to define a new core curriculum to prepare physicians for
      managed care practice.
AB  - All levels of medical education will require modification to address the
      challenges in health care practice brought about by managed care. Because
      preparation for practice in a managed care environment has received insufficient
      attention, and because the need for change is so great, in 1995 the authors
      sought information from a variety of sources to serve as a basis for identifying
      the core curricular components and the staging of these components in the medical
      education process. This research effort consisted of a survey of 125 U.S. medical
      school curriculum deans (or equivalent school representatives); four focus groups
      of managed care practitioners, administrators, educators, and residents; and a
      survey of a national sample of physicians and medical directors. Findings
      indicate that almost all the 91 responding school representatives recognized the
      importance of revising their curricula to meet the managed care challenge and
      that the majority either had or were developing programs to train students for
      practice in managed care environments. The focus groups identified a core set of
      competencies for managed care practice, although numbers differed on whether the
      classroom or a managed care setting was the best place to teach the components of
      a new curriculum. Although medical directors and staff physicians differed with
      respect to the relative levels of importance of these competencies, the findings
      suggest that before medical school, training should focus on communication and
      interpersonal skills, information systems, and customer relations; during medical
      school, on clinical epidemiology, quality assurance, risk management, and
      decision analysis; during residency, on utilization management, managed care
      essentials, and multidisciplinary team building; and after residency, on a review
      of customer relations, communication skills, and utilization management. The
      authors conclude that a core curriculum and its sequencing can be identified,
      that the majority of curricular components exist but in s some cases needed to be
      modified to more clearly relate to managed care practice, and that their findings
      may provide a useful starting point for making decisions about curricular reform.

PMID- 9282141
TI  - Tapping the power of information: an orientation for academic medical centers.
AB  - In September 1994 the Association of American Medical Colleges' (AAMC's) Advisory
      Panel on the Mission and Organization of Medical Schools (APMOMS) established a
      working group to address both the long-term and the immediate implications of the
      expanding capacity of and need for information technology (IT) within academic
      medical centers (i.e., medical schools and teaching hospitals). Over a two-year
      period, group members assessed the utilization of IT through surveys of current
      practices and interactions with acknowledge leaders in the field. They also had
      discussions with deans and other institutional leaders. The group developed the
      consensus that proper use of currently available IT is crucial to virtually every
      aspect of academic medicine's clinical, educational, and research missions.
      Moreover, current IT technology will be further enhanced by the powerful new
      applications that are nearing deployment. All group members agreed that IT must
      become a core competency of academic and medical centers (AMCs), the profession,
      and individual physicians and scientists to ensure the survival of AMCs in the
      current highly competitive environments. The authors outline their arguments for
      the development of strong information systems within AMCs and present basic
      characteristics of systems that show promise for successful implementation. The y
      review some of the major institutional obstacles that have hindered the planing
      and implementation of IT. They conclude with a list of practical institution
      strategies for success in planning and implementing IT systems, and suggestions
      for how the AAMC can help members achieve success in these activities.

PMID- 9282142
TI  - The outcome of medical outcomes assessment: it's not necessarily academic.
AB  - The outcomes assessment movement has the potential to significantly enhance the
      practice of medicine by enabling physicians to identify and implement what works.
      It represents a rich wellspring of material for investigation and is already
      proving to be an important source of research support. As such, it also
      represents a boon to academic medicine, whose activities in patient care,
      research, and education it may enrich. Yet outcomes research may also prove
      itself a threat to academic medicine insofar as the "outcomes" of the academic
      medical center are not adequately represented in its deliberations and
      recommendations. Ultimately, the results of the outcomes movement will be defined
      -both now and in the generation to come--by medicine's guiding vision. It
      behooves those who care about academic medicine to recall that this vision itself
      is a highly prized outcome.

PMID- 9282143
TI  - The importance of preparing medical students to manage different types of
      uncertainty.
AB  - Price competition and other aspects of the changing health care environment are
      threatening many academic health centers (AHCs) and causing them to reassess
      their education and research missions. In order to design effective AHCs for the
      next century, medical leaders must define the unique competencies needed by
      tomorrow's physicians and describe the educational enterprises required to
      produce physicians with these competencies. Two of the most important of these
      competencies are the ability to manage the uncertainty associated with creating
      clinical paradigms and the ability to manage the uncertainty associated with
      managing care delivery. Creating clinical paradigms involves (1) developing
      knowledge about disease categories and (2) developing knowledge about the most
      appropriate therapy for a disease in a particular category. Both these tasks
      involve uncertainty. The second type of uncertainty is associated with managing
      care delivery and is largely a matter of optimizing current clinical paradigms.
      The challenges are (1) to correctly assign patients' diseases to existing disease
      categories, and (2) to correctly choose and manage the delivery of the most
      appropriate therapies to these patients. Currently, AHCs are more competent in
      managing--and educating students to manage--the uncertainty involved in creating
      clinical paradigms. But there is an increasing demand for physicians who manage
      the second type of uncertainty associated with care delivery. The authors
      conclude that in order to remain viable, AHCs, and particularly their medical
      schools, must broaden their educational goals so that students can learn to
      manage both forms of uncertainty.

PMID- 9282144
TI  - Protecting time for teaching in the ambulatory care setting.
AB  - The current drive for efficient clinical teaching threatens the educational
      mission of academic medical centers. With pressures to increase clinical
      productivity, protected time and compensation for teaching have become scarce
      resources for clinical teachers in all settings. Although it may yield new
      approaches to education, the push for efficiency may ultimately result in
      insufficient time for teaching and may cause some clinical preceptors to stop
      teaching completely. Further, it may lead to the illusion that comprehensive
      teaching truly requires little time. Since the future of American health care
      depends upon the provision of high-quality clinical education to young
      physicians, this situation presents a potential national crisis. In this article,
      the authors discuss the complex nature of teaching, its time requirements, and
      the special challenges of teaching in outpatient settings. To avoid
      overemphasizing efficiency to the detriment of education they recommend adhering
      to two principles: (1) academic medical centers are educational as well as
      training institutions, and therefore should provide a broad-based education as
      well as training in clinical skills; and (2) the clinical teaching process is
      complex and adequate time must be provided for its many phases, including
      planning, instructing, and reflecting. Finally, the authors make recommendations
      for ensuring the delivery of high-quality education in ambulatory care settings.

PMID- 9282145
TI  - A pilot course as a model for implementing a PBL curriculum.
AB  - Many medical schools are shifting to a problem-based learning (PBL) curriculum,
      some without any transition period, others using periods of parallel-track
      curricula. The authors report on and discuss a third strategy for implementing
      PBL: using a pilot course as a model to facilitate the transition. After the
      Universite de Montreal Faculty of Medicine chose to switch PBL, one course in the
      third year of the traditional curriculum was changed to PBL format 11 months
      before the new curriculum was to start in September 1993. This was done to
      develop local expertise, to gain confidence, to test the feasibility of the
      method, to produce a showcase, to assess more accurately the resources required,
      and to provide a practice ground for the curriculum planners and managers and the
      faculty-development training team. The authors discuss the planning of the pilot
      course, the training of the faculty in various aspects of PBL (writing problems,
      tutoring methods, etc.), the course implementation, and the course evaluation.
      Overall, the pilot course was well received by both the faculty and the students
      and provided much beneficial information that assisted the university in its
      transition to a new PBL curriculum.

PMID- 9282146
TI  - Dying patients need better doctoring.

PMID- 9282147
TI  - We need federal standards for managed care plans.

PMID- 9282148
TI  - Stress and depressed mood in medical students, law students, and graduate
      students at McGill University.
AB  - PURPOSE: To investigate stress in medical students, law students, and graduate
      students at McGill University using a well-validated measure, the Derogatis
      Stress Profile (DSP). METHOD: The DSP was administered to the medical students in
      November and December 1994. For comparison, the DSP was also administered to the
      undergraduate law students and the graduate students. In November 1995 the DSP
      was administered to the first- and second-year medical students. Results were
      analyzed with a number of statistical methods. RESULTS: The response rates for
      the medical students, the law students, and the graduate students in 1994-95 were
      70%, 96%, and 43%, respectively. The response rate for the first- and second-year
      medical students in 1995-96 was 57%. The medical students had subjective feelings
      of stress that are marginally above population norms, but their total-stress
      scores (related to environmental factors, personality mediators, and emotional
      responses) were below those of the general population, the law students, and the
      graduate students. Elevated depression scores in a minority of the students did
      not seem to be related directly to the stresses associated with medical school.
      The transition from basic science training to clinical training was associated
      with an increase in stress and depressed mood. CONCLUSION: Medical students are
      not greatly stressed relative to other groups, hence other explanations must be
      sought for the elevated levels of depression in some students. One situation in
      which stress appears to be particularly important is in the transition from basic
      science training to clinical training. Targeted interventions may be an effective
      way of dealing with this problem.

PMID- 9282150
TI  - The educational value of an OSCE in a family practice residency.
AB  - PURPOSE: To assess the educational value of an objective structured clinical
      examination (OSCE) administered in three consecutive years (1992-93 to 1994-95)
      to first-year residents in a family practice residency. METHOD: Each year an OSCE
      was administered early in a family practice residency based at the University of
      North Carolina at Chapel Hill School of Medicine. The OSCE encompassed eight to
      ten stations, each 15 minutes long: ten minutes for tasks and five minutes for
      feedback. After the OSCE, focus groups with participating faculty and residents
      assessed the strengths and weakness of specific stations as well as the overall
      OSCE structure. Each year the residents' OSCE scores were correlated with their
      scores on the American Board of Family Physicians In-Training Examination (ITE).
      Pearson product--moment correlation coefficients were calculated for both the
      composite ITE scores and the clinical set problem scores. Test reliability was
      measured by Cronbach's alpha. In the spring of 1995 the faculty completed global
      evaluations of all the residents in the program at the time, including 16 of the
      17 residents who had participated in the OSCEs. The faculty rated the residents
      in four areas, and a four-point scale was based on the percentile ranges a
      resident's rating could fall into for each area. Correlation coefficients were
      calculated for the OSCE scores and the faculty's perceptions of the residents'
      overall performance. RESULTS: The OSCE scores correlated significantly with the
      faculty's global assessments of knowledge and clinical skills, but not with in
      training examination scores. Concurrent validity and reliability estimates did
      not support using an OSCE for decisions about the residents' competency. The
      faculty valued the opportunity to observe basic skills for the whole group of
      residents; the residents found the experience educational but stressful and
      valued the immediate performance feedback included at each station. CONCLUSION:
      The OSCE is a useful tool for teaching basic clinical skills and for forming
      initial impressions of interns' clinical styles and abilities, but it should be
      used with caution for summative assessments.

PMID- 9282149
TI  - An objective structured clinical examination for evaluating psychiatric clinical
      clerks.
AB  - PURPOSE: To assess the feasibility, reliability, and validity of an objective
      structured clinical examination (OSCE) for psychiatric clinical clerks. METHOD:
      In 1995 two parallel forms of a ten-station OSCE (eight clinical stations, two
      writing stations) were developed at the University of Toronto Faculty of Medicine
      Each 12-minute performance-based clinical station was assessed by a faculty
      psychiatrist using both a checklist for each student's performance content and a
      global-rating scale of the performance process. The students' clinical-station
      scores were calculated as the average of their content and process scores
      (expressed as percentages). Examiners also recorded an overall judgment of each
      students' performance (pass, borderline, or fail) and wrote [in collaboration
      with the standardized patient (SP) at that station] comments on each student's
      performance. There were two criteria for a passing grade: a total mark of 60% or
      higher across all ten stations and a "pass" or "borderline" mark in at least five
      of the eight clinical stations. Each OSCE form was administered three times.
      RESULTS: The first form was used to examine 94 clerks, the second form to examine
      98 clerks. The students' mean scores for the two forms were 70.47% (SD, 6.33%)
      and 67.66% (SD, 7.05%), respectively. In addition to the standard evaluation
      information collected on the students, several critical incidents occurred (e.g.,
      a student's loss of control of emotions) that may identify potential problems in
      professional conduct. The direct cost for one administration of the examination
      was approximately Can$3,300: the largest portion of this was for the SPs' time
      spent in training and performing their roles. CONCLUSION: Preliminary evidence
      suggests that a psychiatry OSCE is feasible for assessing complex psychiatric
      skills. However, careful attention must be paid to SP training, examination
      monitoring, detection of critical incidents, and provision of feedback to
      students, faculty, and SPs. The university's previous system of oral examinations
      required approximately 600 faculty hours per year. The OSCE requires
      approximately 450 faculty hours, and the 150 hours saved almost cover the
      Can$20,000 that the examination costs each year. In all, the OSCE is an
      evaluation system that has demonstrable reliability and is more enjoyable for
      both the faculty and the students.

PMID- 9282152
TI  - Assessing medical students' perceptions of mistreatment in their second and third
      years.
AB  - PURPOSE: To study medical students' perceptions of mistreatment in their second
      and third years of training. METHOD: A questionnaire was distributed at Wayne
      State University School of Medicine to the class of 1993 at the end of its third
      year and to the class of 1994 at the end of its second and third years. The
      students were asked if they had been subjected to various forms of mistreatment;
      the third-year students were asked to rate their perceptions of each clinical
      department's response to them on the basis of gender and race-ethnicity, as well
      as their overall treatment. The students also completed demographic information
      about age, gender, and marital status, number of children, and race-ethnicity.
      Results were analyzed using chi-square statistics, multivariate statistical
      analyses, analyses of variance, and Duncan's post-hoc comparisons. RESULTS: The
      response rate for the class of 1993 was 71.5%; response for the class of 1994
      were 66.9% in their second year and 75.2% in their third year; 41.7% were women,
      and the racial-ethnic breakdown was 71.2% white/Caucasian, 11.7% black/African
      American and 16.8% other. There was a significant difference between the
      percentages of second-year and third-year students reporting any experience of
      mistreatment (37.2% vs 75.8%, p < .001). Canonical correlation analysis revealed
      bias in the third year based on gender (p < .0001) and race-ethnicity (p <
      .0002); both variates were related to sexual humor. The students' perceptions of
      mistreatment were lowest for family medicine and highest for obstetrics
      gynecology and surgery. Perceptions of mistreatment in departments varied
      significantly by gender and race-ethnicity. The nonwhite males reported the least
      favorable treatment in most departments. CONCLUSION: Marked variability in the
      students' perceptions of mistreatment within departments suggest that a variety
      of approaches will be required to improve the medical training environment.

PMID- 9282151
TI  - A comparison of two methods to teach smoking-cessation techniques to medical
      students.
AB  - PURPOSE: To evaluate two smoking-cessation practice exercises, one using
      standardized patients (SPs), the other using role playing by medical students.
      METHOD: In the spring of 1994 all 120 first-year University of California, San
      Francisco, School of Medicine Students were given lectures on the health effects
      of smoking and how physicians can help patients quit. Afterward some of the
      students were randomly assigned to two groups in which to practice counseling
      patients: Group 1 (n = 35) used SPs, Group 2 (n = 37) used role playing. Each of
      the Group 1 students practiced smoking-cessation techniques with an SP; the SP
      evaluated the student on cognitive and communication skills, assigned an overall
      rating, and provide feedback using a standardized form. The Group 2 students (as
      well as the 48 students not assigned to a group) role-played in pairs and used
      the same form to provide feedback. All the students evaluated their respective
      practice practices. Two weeks later 24 Group 1 and 31 Group 2 students
      participated in a clinic-skills-assessment exercise using SPs. As in the Group 1
      practice exercise, each student was evaluated by an SP on cognitive and
      communication skills and assigned an overall rating. Data were analyzed through a
      number of statistical methods. The cost of the SP program was determined.
      RESULTS: The Group 1 students rated their practice exercise much more favorably
      than did the Group 2 students. However, there was no significant difference
      between the groups in their ratings by the SPs on the clinical-skills-assessment
      exercise. The use of SPs cost a great deal more than did the use of role playing.
      CONCLUSION: Although the students rated the SPs higher than they did the role
      playing, the two tools produced similar levels of skills attainment. The data
      suggest that having students practice smoking-cessation techniques through role
      playing may be as effective as using the more extensive SPs.

PMID- 9282153
TI  - The performance of students selected through a special program at St. Louis
      University School of Medicine.
AB  - PURPOSE: To compare the performances of students selected through a special
      program, the Medical Anatomy Preparatory Program (MAPP), at St. Louis University
      School of Medicine with those of students admitted at the traditional way.
      METHOD: The students were members of the classes of 1993-1996 at the St. Louis
      University School of Medicine (N = 654). Of these, 52 (8%) were MAPP students.
      The MAPP students and the non-MAPP students were compared on the basis of various
      test scores and grades obtained from the admission office, the registrar's
      office, and the office of curricular affairs. Means and standard deviations were
      computed for each group, and the MAPP students and the non-MAPP students were
      compared using analysis of variance to assess the statistical significance of any
      differences. RESULTS: The non-MAPP students were significantly better than were
      the MAPP students in terms of Medical College Admission Test scores,
      undergraduate gradepoint averages, grades for three major second-year courses,
      and performances on Steps 1 and 2 of the U.S. Medical Licensing Examination (all
      p < .001). There was no significant difference between the groups in grades for
      three major first-year courses or five major third-year courses. None of the MAPP
      students has been dropped for academic reasons. CONCLUSION: The MAPP program
      takes medical school applicants who have been rejected because of their
      preadmission performances, given them the opportunity to show that they can
      perform at the medical school level by taking the anatomy courses with the
      regular medical students, and accepts those who are successful. The results
      suggest that those chosen can satisfactorily complete the requirements for the MD
      degree.

PMID- 9282154
TI  - Liver transplantation: review of the literature. Part 2: Vascular and biliary
      complications.
AB  - The first attempted human orthotopic liver transplantation, in 1963, involved a
      child with biliary atresia, who died on the operating table as a result of
      uncontrollable coagulopathy. Improvements in immunosuppression, surgical
      technique, medical imaging and postoperative care, as well as more stringent
      patient selection, have allowed the development of liver transplantation and its
      universal acceptance as the treatment for a variety of liver diseases. The
      radiologist plays a major role in the multidisciplinary transplantation team and
      must be familiar with each stage of orthotopic liver transplantation and its
      associated complications. In the first article of this series (Can Assoc Radiol J
      1997;48[3]:171-178), the authors reviewed the anatomic features and current
      concepts relevant to orthotopic topic liver transplantation. In this, the second
      article, they discuss the vascular and biliary complications of the operation,
      and the third article will cover the medical complications.

PMID- 9282155
TI  - Malignant stromal cell tumor of the duodenum: clinico-radiologic-pathologic
      conference.

PMID- 9282156
TI  - Spiral spin-echo magnetic resonance imaging of the pelvis with spectrally and
      spatially selective radiofrequency excitation: comparison with fat-saturated fast
      spin-echo imaging.
AB  - OBJECTIVE: The authors describe their initial clinical experience in comparing a
      spiral spin-echo technique with a fat-saturated fast spin-echo technique for
      imaging the pelvis. METHODS: A total of 18 patients were imaged with both spiral
      spin-echo and fat-saturated fast spin-echo magnetic resonance imaging. The spiral
      spin-echo technique combines a spectrally and spatially selective radiofrequency
      excitation with a spiral k-space trajectory. This technique permits rapid
      acquisition of T2-weighted water-only images. RESULTS: The spiral spin-echo
      images were judged superior to the fat-saturated fast spin-echo images in terms
      of uniformity of fat suppression and absence of flow-related artifacts. However,
      the overall image quality of the spiral spin-echo images was inferior to that of
      the fat-saturated fast spin-echo images, as a result of blurring caused by off
      resonance effects. The two techniques were judged equivalent in terms of
      conspicuity of the abnormality and diagnostic information. CONCLUSION: The
      authors conclude that the spiral spin-echo technique holds promise, particularly
      if combined with a deblurring algorithm.

PMID- 9282157
TI  - Stratification of prostate-specific antigen level and results of transrectal
      ultrasonography and digital rectal examination as predictors of positive prostate
      biopsy.
AB  - OBJECTIVE: To determine which of several variables--age, serum level of prostate
      specific antigen (PSA), findings of transrectal ultrasonography (TRUS) and
      findings of digital rectal examination (DRE)--are the best predictors of positive
      prostate biopsy results. SETTING: An urban, university-affiliated tertiary care
      hospital. PATIENTS: a cohort of 1330 consecutive men referred to the diagnostic
      imaging department for TRUS and TRUS-guided prostate biopsy. Each patient was
      referred after examination by a urologist because of clinical suspicion of
      prostate cancer. METHODS: All of the men had undergone prior determination of
      serum level of PSA. Repeat DRE was performed at the time of imaging. The
      variables age, PSA level, TRUS findings and DRE findings were tested aline and in
      combination as predictors of positive biopsy results by means of logistic
      regression analysis. A summary of percentage risk for positive biopsy results was
      constructed for each combination of statistically significant variables,
      stratified for age. RESULTS: Cancer was detected in 541 men (40.7%). A strong
      correlation was observed between serum PSA level and the likelihood of positive
      biopsy result (p < 0.001). Of 402 men with normal age-specific PSA, 109 (27.1%)
      had positive biopsy results. Of 403 men with PSA of 10 ng/mL or more, 233 (57.8%)
      had cancer. The level of serum PSA was also related to the number of prostate
      sextants harbouring cancer (p < 0.001). TRUS findings at the time of biopsy were
      a strong predictor of cancer of the PSA level was abnormal (p < 0.001). DRE
      results alone did not correlate with positive biopsy results, regardless of age,
      PSA level of TRUS findings. CONCLUSIONS: Men in whom there is a clinical concern
      for prostate cancer should undergo prostate biopsy if there is any elevation of
      age-specific PSA, particularly if the findings of TRUS are also abnormal. Because
      DRE alone was not predictive of biopsy outcome, algorithms for prostate cancer
      detection that rely on abnormal DRE results to identify men who should undergo
      biopsy will miss a significant number of cancers.

PMID- 9282158
TI  - Complications after gastric transposition in children.
AB  - BACKGROUND AND OBJECTIVE: Esophagogastrostomy with gastric transposition, a
      procedure for replacement of the esophagus in cases of esophageal atresia, is
      increasing in popularity among pediatric surgeons. This study was undertaken to
      document the differences between postoperative complications in children and
      those reported in adults. PATIENTS AND METHODS: The authors reviewed the medical
      records and radiologic images for details of complications in 6 children (5 boys
      and 1 girl) who underwent esophagogastrostomy with gastric transposition for
      esophageal atresia. Follow-up ranged from 18 months to 12 years. The observations
      were compared with complications in adults, as reported in the literature.
      RESULTS: The complications of gastric transposition were classified as early (up
      to 1 month after surgery) of late (more than 1 month after surgery). They
      included anastomotic leak (in 1 patient), hernia (in 1) and recurrent structure
      (in 3). In 1 patient mediastinal abscess developed secondary to esophageal
      perforation, which occurred during a dilation procedure for stricture.
      CONCLUSIONS: Postoperative complications of gastric transposition occur less
      commonly in children than in adults. Benign stricture, which may occur both early
      and late, is the most common problem.

PMID- 9282159
TI  - The radiographic prevalence of hilar and mediastinal adenopathy in adult cystic
      fibrosis.
AB  - BACKGROUND: It has been stated that the hilar and mediastinal lymph nodes in
      adults with cystic fibrosis are invariably enlarged from chronic inflammation.
      However, until correlation with computed tomography and magnetic resonance
      imaging became possible, the visualization of this feature on plain chest
      radiographs received very little attention, and even the advent of these
      modalities, little has been written on the subject. OBJECTIVE AND METHODS: To
      determine the frequency of positive radiographic evidence of hilar and
      mediastinal adenopathy, the chest radiographs of 48 adult patients with cystic
      fibrosis were reviewed. RESULTS: Adenopathy was found in a total of 25 (52%) of
      the patients hilar in 22 (46%) and mediastinal in 21 (44%). The adenopathy was
      chronic and slowly progressive in all of the patients, and in no case did it
      resolve. The distribution of the adenopathy resembled sarcoidosis in 19 of the 25
      patients and lymphoma in another patient. CONCLUSIONS: The diagnosis of
      adenopathy was thought to be acceptably accurate: among patients for whom CT
      scans were also available, CT confirmed the radiographic diagnosis of abnormality
      in 22 of 24 sets of hilar lymph nodes and all 14 sets of mediastinal lymph nodes.
      When observed on chest radiography, mediastinal adenopathy was invariably
      widespread throughout the mediastinum. The presence of adenopathy was correlated
      with more severe pulmonary involvement, as assessed by the Brasfield scoring
      system. However, the importance of observing adenopathy radiographically lies in
      allaying concerns about the development of sarcoidosis or systemic lymphatic
      disease in these patients and preventing unnecessary concern and investigation.

PMID- 9282160
TI  - Ascending aortic pseudoaneurysm masquerading as pulmonary embolus: case report.

PMID- 9282162
TI  - [Proceeding of the 30th annual musculoskeletal tumor meeting of the Japanese
      Orthopedic Association. Nagoya, Japan. July 18-19, 1997. Abstracts].

PMID- 9282161
TI  - Residents' corner. Answer to case of the month #50. Exogenous lipoid pneumonia.

PMID- 9282163
TI  - Why: gene therapy?

PMID- 9282164
TI  - HVJ (Sendai virus)-cationic liposomes: a novel and potentially effective liposome
      mediated technique for gene transfer to the airway epithelium.
AB  - We designed a novel technique for targeted gene transfer into the airway
      epithelium. This was constructed using multilamellar cationic liposomes,
      containing N-(alpha-trimethylammonioacetyl)-didodecyl-D-glutamate chloride,
      phosphatidylcholine and cholesterol and fused with haemagglutinating virus of
      Japan (HVJ), namely HVJ cationic liposomes. Single aerosol delivery of this novel
      vector to the airway of rats led to a highly efficient and widespread
      transduction of fluorescein isothiocyanate-labeled oligonucleotides or lacZ gene
      into the bronchial epithelium and alveolar macrophages, but not into the alveolar
      epithelium. The efficiency of gene transfer to the airway epithelium with a
      single administration of the lacZ gene was about 47.6% in the trachea, 39.0% in
      the bronchi and proximal bronchioli, and 2.9% in the terminal bronchioli,
      respectively (mean value, n = 6). Expression level of the luciferase gene
      delivered with this novel system was much higher than that without HVJ, in both
      the trachea and lung tissue. Two pretreatment HVJ-cationic liposome vehicles
      every other week resulted in minimal inflammatory infiltration in the sub
      epithelial layer with no significant reduction in efficiency of the following
      gene transfer. We propose that this novel HVJ cationic liposome-mediated gene
      transfer system may be suitable for clinical gene therapy to treat subjects with
      lethal lung diseases such as cystic fibrosis.

PMID- 9282165
TI  - Ex vivo adenovirus-mediated gene transfer and immunomodulatory protein production
      in human cornea.
AB  - One attractive strategy to prevent or control allograft rejection is to
      genetically modify the donor tissue before transplantation. In this study, we
      have examined the feasibility of gene transfer to human corneal endothelium,
      using a number of recombinant adenovirus constructs. Ex vivo infection of human
      corneas with adenoviral vectors containing lacZ, under transcriptional control of
      either cytomegalovirus (CMV) or Rous sarcoma virus (RSV) promoters, provided high
      level gene expression, which was largely restricted to endothelium. Expression of
      the reporter gene persisted at relatively high levels for up to 7 days, followed
      by a decline to indetectable levels by 28 days. RT-PCR analysis of lacZ
      transcription showed a similar picture with a short period (3-7 days) of RNA
      transcription after infection. In contrast, adenoviral DNA persisted for at least
      56 days. Subsequently, we examined the expression of a potential therapeutic
      gene, CTLA-4 Ig fusion protein. Following infection of human corneas with
      adenoviral vectors encoding CTLA-4 Ig protein, high levels of the fusion protein
      were detected in corneal culture supernatants for up to 28 days. This protein was
      functionally active, as determined by binding to B7.1 (CD80)-expressing
      transfectants. This study suggests that genetic alteration of donor cornea before
      transplantation is a feasible approach for preventing or controlling allograft
      rejection. Similar gene-based strategies might also be feasible to prevent
      rejection of other transplanted tissues or organs.

PMID- 9282166
TI  - Spatial-temporal patterns of gene expression in mouse skeletal muscle after
      injection of lacZ plasmid DNA.
AB  - Gene therapy for muscular diseases requires the efficient transfection of a large
      proportion of myofiber cells within a given muscle. In the present experiments,
      patterns of beta-galactosidase expression were examined in mouse rectus femoris
      muscles at various time-points after a single injection of lacZ encoded plasmid
      DNA. beta-Galactosidase expression was detected 3 h after injection and rose to
      peak levels at 3-14 days, and then stabilized at lower levels. beta-Galactosidase
      staining was detected in an average of about 6% (up to 15%) of the total 4000
      myofiber cells, and in about 70% of those myofibers located in the discrete area
      containing the greatest proportion of transfected cells. Soon after injection of
      DNA encoding cytoplasmic or nuclear-targeted beta-galactosidase, expression was
      noted predominantly in the myotendinous junction areas, after which beta
      galactosidase activity progressed toward the central parts of the myofibers. This
      preferential transgene expression at the myotendinous junction may result from
      some unique, local property of the myofiber cells and/or from a restricted
      diffusion or binding of the injected plasmid DNA at tendinous surfaces. A better
      understanding of the reasons for this pattern of reporter gene expression in
      muscle may suggest procedures for increasing the number of myofiber cells
      transfected by direct DNA injections.

PMID- 9282167
TI  - Selection and use of ligands for receptor-mediated gene delivery to myogenic
      cells.
AB  - Identification of myogenic cell targeting ligands is a critical step in the
      development of synthetic vectors for gene delivery to skeletal muscle. Here we
      describe the screening of six potential targeting ligands (insulin, insulin-like
      growth factor I, iron transferrin, gallium transferrin, alpha-bungarotoxin and
      carnitine) for their ability to bind dystrophin-deficient myotubes in vitro.
      Those ligands showing high levels of binding to myotubes were then tested on
      fully differentiated, isolated, viable myofibers. Of the ligands tested,
      transferrin showed the most promise based on high levels of binding to myogenic
      cells, high levels of receptor observed in regenerating fibers of patients with
      Duchenne muscular dystrophy and the ability to direct a large enzyme conjugate to
      the cytoplasm of myotubes. Finally, we show that incorporation of transferrin
      into an artificial virus consisting of poly-L-lysine-condensed DNA coated with a
      lipid shell (LPDII formulation) results in ligand-directed delivery of DNA to
      myogenic cells. This is the first report of gene transfer to myogenic cells using
      a ligand-directed synthetic vector. These results suggest that rational design of
      ligand-directed, fully synthetic, gene delivery vehicles is a viable approach to
      skeletal muscle vector development.

PMID- 9282168
TI  - Cancer gene therapy using a novel adeno-associated virus vector expressing human
      wild-type p53.
AB  - Previous studies have indicated that transfer of wild-type (wt) p53 cDNA into
      cancer cells can suppress the tumor phenotype in vitro and in vivo. In this study
      we examined the effects of wt p53 transduction in the human cancer cell line H
      358 (that bears a homozygous deletion of p53) using a novel recombinant adeno
      associated viral vector engineered to express wt p53 (rAAVp53). Western blot
      analysis demonstrated the expression of wt p53 in H-358 cells following infection
      with rAAVp53. Furthermore, rAAVp53 inhibited the growth of the neoplastic cells
      and also mediated cytotoxicity. Cell cycle analysis of rAAVp53-infected cells
      showed a significant increase in the percentage of cells arrested at the G1-S
      checkpoint. H-358 cells infected with rAAVp53 underwent apoptosis as demonstrated
      by the morphological appearance of DAPI-stained nuclei. Direct injection of
      rAAVp53 into H-358 tumors implanted subcutaneously in immunodeficient nu/nu mice
      inhibited tumor growth completely in three of the five animals tested. Mock
      infected and rAAV control treated tumors showed no growth inhibition. In situ
      staining in nu/nu mice detected the presence of wild-type p53 protein in residual
      tumor cells following rAAVp53 administration. The impressive in vivo efficacy of
      the rAAVp53 suggests a bystander effect. We conclude that rAAV may be effective
      as a gene transfer vector in the delivery of p53 to cancer cells.

PMID- 9282169
TI  - Rescue of photoreceptor function by AAV-mediated gene transfer in a mouse model
      of inherited retinal degeneration.
AB  - Knowledge of the mutations leading to inherited retinal degenerations provides a
      foundation for the development of somatic gene therapy in which potentially
      corrective genes are transferred to the target photoreceptor cells. Towards this
      end, we have evaluated the efficacy of a recombinant adeno-associated virus (AAV)
      vector to deliver and express the correct form of the cGMP phosphodiesterase-beta
      (PDE-beta) gene in the retinas of rd mice, which suffer rapid retinal
      degeneration due to recessive mutation in the endogenous gene. A truncated murine
      opsin promoter was used to drive expression of the PDE-beta cDNA. Following
      intraocular injection of AAV. PDE-beta, increased retinal expression of
      immunoreactive PDE protein was observed, including within photoreceptor cell
      bodies. Compared with age-matched controls, treated eyes showed increased numbers
      of photoreceptors and a two-fold increase in sensitivity to light as measured by
      in vitro electroretinography. These findings provide evidence that rescue of
      functional photoreceptor neurons can be achieved by somatic gene therapy.

PMID- 9282170
TI  - Enhanced immune costimulatory activity of primary acute myeloid leukaemia blasts
      after retrovirus-mediated gene transfer of B7.1.
AB  - Gene modification of malignant cells to express immune stimulators (cytokines and
      immune costimulators) has provided the basis for a novel form of immunotherapy.
      Using a MPSV-based retroviral vector with hygromycin resistance gene as a
      selectable marker, we have studied retrovirus-mediated gene transfer of an immune
      costimulator, B7.1, into primary human acute myeloid leukaemia (AML) cells and
      the subsequent induction of immune costimulatory function. AML blasts from 10
      patients were transduced by co-culture for 48 h with or without haemopoietic
      growth factors (HGFs). In the absence of HGFs, transduction efficiency (TE), as
      judged by % B7.1 expressing cells, was low, varying from 0.3 to 8.2% (median
      1.5%). Addition of HGFs increased the median TE 1.8-fold with stem cell factor
      alone and 2.6-fold with SCF, interleukin-3 and GM-CSF. Effects on cell cycling
      alone could not explain this difference, suggesting other factors such as virus
      binding and promoter activity, are also involved. CFU-AL assays indicated a
      higher transduction efficiency of clonogenic cells, which was not improved by
      growth factors. Limited duration of cell growth prevented significant expansion
      of transduced populations by culture in the presence of hygromycin. Although not
      increasing transduction efficiency, CD34 enrichment enhanced drug selection, by
      targeting cells with the greatest self-renewal capacity. Immunoselection of B7.1
      expressing cells produced transduced populations with 30-60% expressing B7.1. In
      an allogeneic mixed leukaemic cell/T lymphocyte reaction (MLLR) transduced AML
      cells enriched by immunoselection were able to stimulate allogeneic T cells (CD4
      and CD8 positive), which could be inhibited by a solubilised B7 receptor,
      CTLA4.Ig. Our results demonstrate that using a replication incompetent retroviral
      vector, it is possible to introduce the immune costimulator B7.1 into primary AML
      blasts and by immunoselection, enrich the transduced cells, which may be used for
      subsequent administration as an autologous cellular vaccine.

PMID- 9282171
TI  - Efficient gene targeting in mouse embryonic stem cells.
AB  - We developed methods to improve the efficiency of gene correction in mouse
      embryonic stem cells using homologous recombination of a replacement vector. The
      absolute frequency of homologous recombination in mouse embryonic stem (ES)
      cells, defined as the frequency of homologous recombination per electroporated
      cell, is approximately 10(-5) to 10(-6) by current procedures. Our method for
      gene targeting in mouse ES cells produces an absolute frequency of 10(-1). The
      protocol uses micro-electroporation chambers and a modified electroporation
      procedure that does not cause significant cell death. Plating and growth of the
      electroporated cells at an optimum density to maintain viability significantly
      increased the recovery of targeted cells. Due to the high frequency of targeting,
      corrected cells could be isolated by screening colonies obtained after growth
      without selection. Alternatively, colony formation and the absolute frequency
      could be increased by co-plating the electroporated cells with nonelectroporated
      ES cells before the addition of selective medium. These parental cells were
      nonirradiated but were killed in the selective medium. Plating density and
      efficiency of colony formation are therefore critical factors for obtaining a
      high absolute frequency of homologous recombination. Because this frequency is
      extremely high, these methods can be used to perform gene targeting without the
      use of selectable markers.

PMID- 9282172
TI  - Shock wave permeabilization as a new gene transfer method.
AB  - Uptake of naked functional DNA into mammalian cells can be achieved by a number
      of physical methods. However, for most of these techniques possibilities for
      therapeutic in vivo applications--especially to solid organs--are often limited.
      In this report, we describe shock wave permeabilization as a new physical gene
      transfer method, which can be easily applied, provides great flexibility in the
      size and sequence of the DNA molecules to be delivered, and which should exhibit
      an advantageous security profile in vivo. Upon exposure to lithotripter-generated
      shock waves eukaryotic cells display a temporary increase in membrane
      permeability. This effect was shown to be caused by cavitation resulting in the
      transient generation of cell pores which allows the direct transfer of naked
      plasmid DNA. Shockwave transfection of a variety of cell lines was demonstrated.
      Since shock waves can be well focused within particular body regions, future
      applications of extracorporally generated shock waves to tissues simultaneously
      perfused with DNA solutions might open up the possibility of achieving a
      regionally enhanced in vivo gene transfer.

PMID- 9282173
TI  - Effect of co-lipids in enhancing cationic lipid-mediated gene transfer in vitro
      and in vivo.
AB  - Complexes of DNA and cationic lipids are promising vectors for gene transfer.
      Most cationic lipid formulations contain both a cationic component and a neutral
      co-lipid. We found that the co-lipid could influence DNA uptake in COS-1 cells,
      but processes subsequent to uptake were even more important in determining gene
      expression. We compared dioleoylphosphatidylethanolamine (DOPE) and structural
      analogs of DOPE combined with cationic lipids and found that DNA uptake and
      transgene expression did not always correlate. Transgene expression was dependent
      on DNA uptake into the cell, on entry of DNA into the cytoplasm, and on release
      of DNA from the lipid complex. We found that some co-lipids had a greater effect
      on DNA uptake, whereas others had a greater effect on steps subsequent to entry.
      Based on those results, we tested the hypothesis that co-lipids conferring
      different properties could be combined to enhance gene transfer. The results
      showed that a combination of co-lipids had a synergistic effect on expression. We
      also found that structural analogs of DOPE were more effective than DOPE in
      enhancing gene transfer to mature human airway epithelia studied in vitro and to
      mouse lung studied in vivo. These data provide insight into the mechanism by
      which co-lipids influence cationic lipid-mediated gene transfer and show that
      optimization of the effects of co-lipids can enhance gene transfer both in vitro
      and in vivo.

PMID- 9282174
TI  - Gene transfer of the costimulatory molecules B7-1 and B7-2 into human multiple
      myeloma cells by recombinant adeno-associated virus enhances the cytolytic T cell
      response.
AB  - Gene transfer of the costimulatory molecules B7-1 and B7-2 induces a potent
      antitumor immune response in a variety of tumor models. B cell neoplasms
      including multiple myeloma (MM) often show little or no expression of B7
      antigens; they are therefore a potential target for this approach. To increase
      the expression of human B7 genes in MM cells, both genes and the neomycin
      phosphotransferase gene were packaged into recombinant adeno-associated virus
      vectors (rAAV). The resulting recombinant viruses rAAV/B7-1, rAAV/B7-2 and
      rAAV/Neo were used to transduce the MM cell lines LP-1 and RPMI 8226. This
      allowed the transduction of up to 80% of LP-1 cells 4 days after infection with
      purified rAAV particles. The response of human allogeneic T cells to rAAV/B7-1
      and rAAV/B7-2 transduced, gamma-irradiated LP-1 cells was assessed by
      [3H]thymidine incorporation, by RT-PCR-based detection of immunostimulatory
      cytokine transcripts and by ELISA quantification of cytokines in the supernatant.
      Stimulation of T cells with rAAV/B7-1 or rAAV/B7-2 transduced LP-1 cells resulted
      in an up to 10-fold increase of T cell proliferation when compared with LP-1
      cells transduced with rAAV/Neo. Similar results were obtained with RPMI 8226
      cells. Both rAAV/B7-1 and rAAV/B7-2 transduced LP-1 cells stimulated the T cell
      secretion of IL-2 and IFN-gamma. Furthermore, [51Cr] release assays showed that
      rAAV/B7-1 or rAAV/B7-2 transduced LP-1 cells induced a cytolytic T cell (CTL)
      response, in contrast to LP-1 cells transduced with rAAV/Neo. In all assays, the
      effects of rAAV/B7-1 and rAAV/B7-2 were similar. Taken together, the results show
      that rAAV-mediated transfer of B7 genes into MM cell lines is able to enhance the
      antitumor T cell response and to elicit a cytolytic T cell response.

PMID- 9282175
TI  - Intracellular application of hairpin ribozyme genes against hepatitis B virus.
AB  - HBV, a partially double-stranded DNA virus, replicates through a pregenomic RNA
      (pgRNA) intermediate, which provides a therapeutic opportunity for a novel
      antiviral gene therapy based on ribozyme RNA cleavage. Three hairpin ribozymes
      (Rzs) were designed which have the potential to disrupt HBV replication by
      targeting the pgRNA as well as specific mRNAs encoding the HBV surface antigen
      (HBsAg), the polymerase and the X protein. The ability of each ribozyme to cleave
      approximately 0.3 kb HBV subgenomic RNA fragments was tested in vitro. Two of the
      three Rzs tested (BR1 and BR3) were capable of cleaving their respective RNA
      substrates, while their catalytically disabled mutated counterpart Rzs were not.
      Structural modifications were performed on these two Rzs, with the goal of
      increasing catalytic efficiency both in vitro and in cells. To determine the Rz
      activities in liver cells, the cDNAs for each of the anti-HBV Rzs (and their
      catalytically disabled negative controls) were cloned into retroviral vectors.
      Unmodified ribozymes co-expressed with HBV in human liver Huh7 cells reduced the
      level of viral particle production by up to 66% based on the endogenous
      polymerase assay, while the structurally modified ribozymes inhibited HBV
      production up to 83%. These encouraging results indicate the feasibility of
      ribozyme-mediated gene therapy for the treatment of HBV infections.

PMID- 9282176
TI  - A rapid screening procedure for the identification of high-titer retrovirus
      packaging clones.
AB  - We have developed a viral RNA (vRNA) dot blot assay for rapid identification of
      high-titer retrovirus vector production by packaging cell clones. The procedure
      employs Trizol LS reagent to purify vRNA from packaging cell supernatants, a
      sensitive dot blot assay, and Phosphorlmager technology to quantify packaged
      viral genomes in 2 days. Experiments performed on viral supernatants of known
      biological titer demonstrated that the vRNA dot blot assay was extremely
      sensitive and that dot intensity correlated directly with viral titer. It is
      often necessary to analyze approximately 100 virus producing cell clones, making
      this method useful as a rapid screen to identify the highest virus producing
      clones. The vRNA dot blot assay consistently identified a subset of candidate
      high-titer producer cell clones. In three independent screens the supernatant
      with the highest biological titer was produced by one of the previously defined
      candidate high-titer producer clones. Our procedure greatly facilitates virus
      titration by: (1) rapidly eliminating the vast majority of low-titer producer
      cell clones; (2) accurately identifying the subset of candidate high-titer
      producer clones for further biological titration and assessment of the proviral
      genomic structure; and (3) reducing laborious tissue culture manipulations to a
      minimum. Furthermore, the reliance of this method on molecular detection makes it
      ideally suited for the isolation of high-titer clones lacking a drug selection
      marker.

PMID- 9282177
TI  - Intra-articular fractures of the calcaneum: why such controversy?

PMID- 9282178
TI  - The value of physical examination in the diagnosis of patients with blunt
      abdominal trauma: a retrospective study.
AB  - Between 1 January 1993 and 1 January 1994, 204 consecutive patients with possible
      blunt abdominal injury were analysed retrospectively. All patients underwent a
      standardized diagnostic approach on admission to the emergency room. Abdominal
      ultrasound (AUS) was performed in all cases. If there was evidence of intra
      abdominal injury on physical examination or AUS, without signs of persistent
      hypovolaemia after initial assessment, contrast-enhanced computed tomographic
      scanning (CECT) of the abdomen was carried out without exception. Physical
      examination was equivocal in 13 and 3 per cent, respectively, of patients with
      'isolated' abdominal trauma (N = 23) or with fractures of lower ribs 7-12 as a
      sole diagnosis (N = 30). In multiple injury patients (N = 95) or those with
      suspected 'isolated' head injury (N = 56), these figures reached 45 and 84 per
      cent, respectively. AUS (N = 204) revealed intra-abdominal injury in 20 per cent
      of patients, and CECT (N = 43) resulted in additional information in 49 per cent.
      Patients with 'isolated' head injury showed 9 per cent abnormalities on abdominal
      evaluation versus 32 per cent in multiple injury patients. In lower rib fractures
      (7-12) in multiple injury patients abdominal injury was diagnosed in 67 per cent
      of the cases. We conclude that: (1) negative findings following reliable physical
      examination of patients with 'isolated' head injury show very high values (NPV
      100 per cent), but reliable physical examination is very infrequent (16 per
      cent); (2) NPV in lower rib fractures due to low energy impact is very high (100
      per cent), with a reliable physical examination in most patients (97 per cent);
      (3) in patients with isolated abdominal trauma 87 per cent have a reliable
      physical examination with a moderately high NPV (71 per cent); (4) almost half
      the multiple injury patients have an unequivocal physical examination (45 per
      cent), with a high NPV following reliable physical examination for abdominal
      injury (85 per cent); (5) abdominal ultrasonography should be the first step in
      the radiological assessment of all patients with possible blunt abdominal injury;
      (6) in multiply injured patients with fractures of their lower ribs (7-12) due to
      high energy impact the incidence of abdominal injury is very high and CECT might
      be indicated even in the case of normal AUS findings.

PMID- 9282179
TI  - Bicycle-spoke injuries: a prospective study.
AB  - A prospective study of bicycle-spoke injuries was undertaken to assess the
      severity of soft tissue damage and the incidence of skeletal injuries. During a
      12 month period, 59 children with spoke injuries were examined. Soft tissue
      damage was divided into three categories: bruising without laceration (four),
      bruising and superficial abrasions (49) and full thickness skin defects (six).
      Seventeen children had skeletal injuries: nine tibial fractures (five greenstick
      fractures and four spiral fractures) and eight epiphyseal injuries of the distal
      fibula. All fractures were treated non-operatively. The mean time for soft tissue
      healing was 16.5 days and the mean time for regaining full weight-bearing was 8.5
      days. Soft tissue damage is the most important prognostic factor in the healing
      of a bicycle-spoke injury.

PMID- 9282180
TI  - Revascularization of degloving injuries of the limbs.
AB  - Between 1990 and 1994 a study was carried out of 32 patients who had degloving
      injuries of the limbs. There were three types of injuries: type I, nine patients
      with severely damaged skin and subcutaneous tissue; type II, 13 patients whose
      skin and subcutaneous tissue were moderately damaged, but subcutaneous veins were
      still identifiable; and type III, 10 patients whose skin and subcutaneous tissue
      were moderately damaged and venous back flow was observed. The patients in type I
      were treated by extensive debridement and the flaps were used for free full and
      split thickness skin grafting. In type II, arterialization of the venous system
      of the flaps was performed and successful perfusion was observed in nine
      patients. In type III, venous anastomoses were performed and all had good
      results. Revascularization of the flaps in types II and III degloving injuries of
      the limbs gave good results. The raw surface which needed skin grafting was
      minimized and the course of treatment and morbidity were decreased.

PMID- 9282181
TI  - The fate of the syndesmosis in type C ankle fractures: a cadaveric study.
AB  - Ankle fractures that involve a fracture of the fibula above the syndesmosis (AO
      type C) associated with a medial lesion are always said to indicate rupture of
      the inferior tibiofibular syndesmosis. This study shows that fresh cadaver ankles
      subjected to a combination of abduction and direct lateral force over the shaft
      of the fibula consistently produce displaced bimalleolar ankle fractures without
      disruption of the inferior tibiofibular syndesmosis. The results of this study
      suggest that the presence of an AO type C ankle fracture does not necessarily
      indicate diastasis of the inferior tibiofibular joint and, therefore, internal
      fixation of the syndesmosis of the fracture may not be indicated.

PMID- 9282182
TI  - A more stable posterior approach for hemiarthroplasty of the hip.
AB  - The dislocation rate following the insertion of a hemiarthroplasty of the hip via
      the posterior approach is variously quoted as between 8 per cent and 15 per cent.
      We set out to determine if this could be reduced by preserving the labrum and
      capsular structures at the time of surgery. We used a modification of the
      posterior approach, in which the labrum and capsule are preserved which appears
      not to have been widely reported. This increases the stability of the joint by
      adding to the depth of the acetabulum. We look prospectively at a series of 150
      patients who were treated with an Austin Moore hemiarthroplasty using this
      technique. There were only two dislocations within 1 year of surgery in the
      series (one of these being in a patient with a dysplastic acetabulum) making our
      dislocation rate 1.3 per cent. We conclude that preserving the labrum
      significantly increases the stability of a hemiarthroplasty when it is inserted
      via a posterior approach.

PMID- 9282183
TI  - Is manipulation of moderately displaced Colles' fracture worthwhile? A
      prospective randomized trial.
AB  - Thirty elderly patients with moderately displaced Colles' fractures were randomly
      assigned to manipulation under Bier's block or plaster immobilization alone.
      Moderately displaced was defined as 10 degrees to 30 degrees of dorsal angulation
      and less than 5 mm of radial shortening compared with the uninjured side. The
      groups were well matched for age, sex, fracture type and displacement;
      immobilization time and rehabilitation were standardized. The outcome measures
      were: radiological position at union, the functional score of Gartland and
      Werley, grip strength, cosmesis and algodystrophy assessment. There was no
      detectable difference between the groups in any of the outcome measures. Two
      thirds of the correction of dorsal angulation achieved by manipulation was lost
      by 5 weeks. We conclude that up to 30 degrees of dorsal angulation and 5 mm of
      radial shortening may be accepted in selected elderly patients.

PMID- 9282184
TI  - An audit of the combined non-operative and orthotic management of ruptured tendo
      Achillis.
AB  - At this institution we have introduced combined non-operative and orthotic
      treatment for ruptured tendo Achillis. An outcome audit was performed to assess
      this treatment. Patients were treated in a short-leg cast in the equinus
      position. After a cast period of 4 weeks, the patient was placed in orthoses for
      a further 4 weeks, after which they returned to normal activities as was
      appropriate. We performed a retrospective review including visual analogue scores
      of patient satisfaction and physical examination. Thirty-two patients were
      reviewed. The average time from injury to review was 2 years (range 6 months to
      5.5 years). There were no significant complications following treatment with no
      re-ruptures to date. Average visual analogue scores (0-10) were for casts 5.9,
      orthoses 8.5 and overall outcome 8.3. Of those wishing to return to sporting
      activities 62 per cent did so within 6.6 months (average). Clinical examination
      showed no significant difference (P, 0.05) between normal and injured leg in
      terms of ankle range of movement, tone and subtalar movement. The maximum calf
      circumference was significantly reduced on the affected side (36.84 cm versus
      38.2 cm) as was ankle plantar flexion power. This treatment was liked by patients
      and is at least as effective as other established methods. Calf power and muscle
      bulk were reduced in the affected leg and may be improved by including a
      physiotherapy protocol in the treatment.

PMID- 9282185
TI  - Ipsilateral proximal and shaft femoral fractures: spectrum of injury involving
      the femoral neck.
AB  - Medical records and radiographs of 52 patients were studied after
      inclusion/exclusion criteria were met. The anatomical location of proximal
      femoral fractures that involved the femoral neck were examined after the primary
      fracture planes were drawn onto templates of the proximal femur. The AO
      classification is comprehensive and widely accepted. It has not been used in this
      injury combination in a large series of patients. Therefore, we classified each
      fracture by the AO method and then the AO classes were tabulated and analysed.
      Only three patterns of proximal femoral fractures appeared. The inferior aspect
      of the fracture line clustered in the inferomedial aspect of the femoral neck
      above an intact lesser trochanter in each separate pattern: 55 per cent were AO
      B2.1 (basilar); 35 per cent AO B2.3 (intracapsular); and 10 per cent AO A1.2
      (pertrochanteric) fractures). Eleven fractures (21 per cent) were not detected
      initially. None of these were A1.2, eight were B2.1 and three were B2.3. Despite
      many proximal femoral fracture types reported in the literature only three
      fracture patterns were noted in this large study group. A new finding of
      clustering of these fractures in the inferomedial femoral neck was noted. AO
      class B2.1 fractures were the most common fractures missed at initial
      presentation and were the most common type seen.

PMID- 9282186
TI  - Delayed diagnosis of femoral neck fractures.
AB  - To determine the causes and consequences of any delay from the onset of symptoms
      to diagnosis, 1108 consecutive patients with an acute proximal femoral fracture
      were prospectively studied. In 154 cases (13.9 per cent) the diagnosis was
      delayed more than 24 h from the onset of symptoms. The reason for this was due to
      failure to seek medical help in 63 patients. For the 91 patients who were seen by
      a medical practioner, 60 were not X-rayed straight away. For those cases where a
      radiographic examination was requested, the fracture was invisible in only nine
      cases, of which six subsequently displaced. The diagnosis was more likely to be
      delayed if the fracture occurred spontaneously, the patient fell inside, or the
      fracture was intracapsular. Delay in diagnosis was not associated with an
      increase in mortality but there was a significant increase in the risk of
      pressure sores.

PMID- 9282187
TI  - MRI findings in simultaneous bilateral meniscal lesions.
AB  - This study investigates concurrent lesions of the knee that may be associated
      with bilateral simultaneous meniscal lesions. The MRI images of the knees of 22
      patients with this condition were examined in detail. The results suggest a
      degenerative cause.

PMID- 9282188
TI  - Distal radius fractures: a prospective randomized comparison of fibreglass tape
      with QuickCast.
AB  - Cast immobilization remains the most commonly employed method in the treatment of
      distal radius fractures. In an effort to test a new shrinkable polymer-coated
      casting material (QuickCast), a prospective randomized study was performed on 30
      consecutive distal radius fractures. Fractures were divided into three groups
      based on the severity of fracture and treated with either a conventional short
      arm fibreglass tape cast or a QuickCast. Results showed no significant
      differences in minor cast complications or maintenance of fracture reduction
      between conventional fibreglass tape and the QuickCast material. The shrinkable
      QuickCast, however, resulted in an average of one less cast change in all groups.
      This reduction in time and labour must be weighed against the slightly increased
      cost of the QuickCast immobilizer.

PMID- 9282189
TI  - The incidence of Achilles tendon rupture in Copenhagen.
AB  - The incidence of Achilles tendon rupture in Copenhagen during an 18 year period,
      from 1978 to 1995 was studied. A total of 209 patients sustained 213 Achilles
      tendon ruptures (55 in women and 158 in men). The median age was 41 years. The
      overall incidence was 13.4/100000 inhabitants/year.

PMID- 9282191
TI  - Floating clavicle--simultaneous dislocation of both ends of the clavicle.

PMID- 9282190
TI  - Injury of the cervical spine associated with carotid and vertebral artery
      occlusion: case report and literature review.

PMID- 9282192
TI  - Irreducible Lisfranc's injury: the 'toe up' sign.
AB  - A new physical sign (the 'toe up' sign) is described in relation to an
      irreducible Lisfranc injury, the cause being the interposed lateral slip of the
      tibialis anterior tendon. Surgical exploration is advocated.

PMID- 9282193
TI  - Intramedullary locked nailing of femur and tibia: insertion of distal locking
      screws without image intensifier.

PMID- 9282194
TI  - Neoplastic chemotherapy and head and neck cancer.

PMID- 9282195
TI  - Trends in randomized controlled trials in ENT: a 30-year review.
AB  - There is a growth in the demand for clinical practice to be evidence based.
      Recent years have seen a rise in the number of randomized controlled clinical
      trials (RCTS). Such trials while acknowledged as the gold standard for evidence
      can be difficult to perform in surgical specialities. We have recently identified
      a low proportion of RCTS in the otolaryngology literature. Our aim was to
      identify any trend in the number of published RCTS within the ENT literature over
      a 30-year period and to identify which areas of our speciality lend themselves to
      this form of study design. A Medline search of 10 prominent journals published
      between 1966 and 1995 was performed. Two hundred and ninety-six RCTS were
      identified. Only five were published before 1980. Two hundred (71 per cent) of
      RCTS were in the areas of otology and rhinology. An encouraging trend is seen in
      RCTS within ENT literature.

PMID- 9282196
TI  - Bacterial colonization of pacifiers of infants with acute otitis media.
AB  - The presence of aerobic and facultative anaerobic bacteria on the surface of
      pacifiers used by children with acute otitis media was investigated. The surface
      of 40 recently used pacifiers was swabbed after they were allowed to dry for five
      to six minutes. The swabs were processed quantitatively for the presence of
      aerobic bacteria. The antibacterial activity of the pacifier material was tested
      in vitro. Microorganisms were isolated from 21 (52.5 per cent) pacifiers. The
      number of colonies per pacifier varied between one and 35 (average six). The
      isolates included eight alpha-haemolytic streptococci, six Staphylococcus
      epidermis, five Candida albicans, five alpha-haemolytic streptococci, three
      Neisseria spp. and two Staphylococcus aureus. The pacifier material was shown to
      be inhibitory against S. aureus. This study illustrated that pacifiers do not
      contain high numbers of organisms and therefore are not likely to serve as a
      source of persistence of transfer of organisms.

PMID- 9282198
TI  - Laryngeal tuberculosis at the end of the 20th century.
AB  - Despite the dramatic reduction in the incidence of laryngeal tuberculosis after
      the 1950s, the topic has now gained new interest due to claims that the disease
      has changed its clinical pattern. In the past, the typical patient was 20-40
      years old with ulcerated laryngeal lesions, perichondritis, and advanced cavitary
      lung disease. We studied nine cases of laryngeal tuberculosis confirmed by
      histological examination. The microlaryngoscopy revealed tumour-like lesions
      and/or chronic non-specific laryngitis. There were no significant ulcerations or
      signs of perichondritis. The patients' ages ranged from 48.5 years to 69.3 years
      (mean, 59.4 years). In three of our patients (33 per cent) we did not find any
      pulmonary involvement, thus suggesting primary laryngeal tuberculosis or
      haematogenous spread. In conclusion, the numerous physicians who deal with the
      various laryngeal symptoms and diseases should be aware of the existence of
      laryngeal tuberculosis and the changing patterns of the disease (at least in the
      developed countries).

PMID- 9282197
TI  - Flexible transnasal endoscopy: is local anaesthetic necessary?
AB  - Prior to flexible transnasal endoscopy (FTE) topical intranasal agents such as
      cocaine or combinations of a local anaesthetic and vasoconstrictor agent are
      generally recommended for local anaesthesia, easier access, and better
      examination of the interior of the nose, especially the middle meatus. This
      double-blind study involved 60 patients. Each had five per cent cocaine sprayed
      in one nostril and normal saline in the other. The pain/discomfort and gag scores
      showed no statistical difference. Forty-two (70 per cent) patients had a
      moderate/marked deviation of the nasal septum. A significant pain score (3-5) was
      obtained in 33.3 per cent of cases with the deviation towards the cocaine side
      and in 37 per cent of cases with the deviation towards the saline side. Ease of
      procedure scores for both sides were also comparable, when deviation of the nasal
      septum was taken into account.

PMID- 9282199
TI  - Cyclin D1 protein expression is related to clinical progression in laryngeal
      squamous cell carcinomas.
AB  - The expression of cyclin D1 gene was investigated in 74 laryngeal squamous cell
      carcinomas (LSCCs) in order to determine its clinical and prognostic value.
      Overexpression of cyclin D1 was detected immunohistochemically using DCS6
      monoclonal antibody on formalin-fixed, paraffin-embedded tissue sections. Cyclin
      D1 expression was detected in 22 of the 74 cases investigated (30 per cent),
      thirteen of which presented nodal metastases (59 per cent); of the patients
      without any detectable cyclin D1 protein expression, six presented nodal
      metastases (12 per cent). Cyclin D1 protein expression was found in five per cent
      of the specimens of normal mucosa, eight per cent of those with low-grade
      dysplasia and 20 per cent of those with high-grade dysplasia. A statistically
      significant association was found between cyclin D1 expression and the
      supraglottic site (p < 0.05), tumour extension (p < 0.001), the presence of lymph
      node metastases (p < 0.001), and advanced clinical stage (p < 0.001). Cyclin D1
      expression analysis is an important tool in the selection of LSCC patients with
      an aggressive clinical course.

PMID- 9282200
TI  - Endoscopic laser myotomy in the treatment of pharyngeal diverticula.
AB  - The endoscopic approach is a simple and cost-effective option in the treatment of
      hypopharyngeal diverticula. Whereas almost a third of all endoscopic myotomies
      performed by UK otolaryngologists are carried out with the stapling technique,
      CO2 laser diverticulotomy has not been given as much consideration (Koay et al.,
      in press). We report on the first British series of 15 patients treated between
      1985 and 1993 with microscopic laser diverticulotomy. The follow-up period was
      four to 11 years. Complications occurred in three patients, two patients required
      a repeat myotomy and 11 patients have been satisfied with their swallow since the
      operation. Our results are similar to those of larger studies. The laser
      technique is more established than the stapling gun myotomy and it has the
      advantage of superior visualization. It may also be used in small pouches which
      do not admit the insertion of a stapling gun.

PMID- 9282201
TI  - Cephazolin and metronidazole prophylaxis in head and neck surgery.
AB  - A seven-day course of cephazolin and metronidazole chemoprophylaxis for clean
      contaminated head and neck oncological procedures is compared to results with
      previously published antibiotic regimens. Aetiological factors associated with
      increased rates of wound complications are analyzed. Retrospective analysis of
      procedures over a six-year period was performed. The overall wound complication
      rate was 28.1 per cent, comparing favourably with previously published results. A
      major fistula was the most common complication with a rate of 9.2 per cent.
      Factors statistically associated with increased rates of wound complications
      included: radical neck dissection, extended surgical procedures requiring flap
      reconstruction, previous tracheotomy, and race. This is the largest single
      institutional study to show that a seven-day course of cephazolin and
      metronidazole is an effective chemoprophylactic regimen in head and neck surgery.

PMID- 9282202
TI  - Combined approach intranasal endoscopic and external Lothrop procedure in chronic
      frontal sinus disease.
AB  - The endoscopic approach to the fronto-ethmoidal recess (FER) in the treatment of
      chronic frontal sinus disease is now widely accepted. The Lothrop procedure was
      first described in 1914, but was largely replaced with more invasive open frontal
      sinus procedures until the advent of the rigid Hopkins' rod, since when it has
      enjoyed renewed popularity. We describe a modification of this technique which
      allows both transnasal endoscopic and external direct visualization of the FER
      and frontal sinus and a direct approach to the anterior buttress (or "nasofrontal
      beak") which allows its quick and simple removal.

PMID- 9282203
TI  - Haemangioma of the maxillary sinus.
AB  - Haemangiomas of the maxillary sinus are very rare. In this paper we present one
      case with an inaccurate preoperative diagnosis which was treated by entire
      excision of the tumour. One year after surgery there is no evidence of
      recurrence. The literature on the topic is reviewed.

PMID- 9282204
TI  - A case of a large dentigerous cyst containing a canine tooth in the maxillary
      antrum leading to epiphora.
AB  - A case of a large dentigerous cyst containing a canine tooth in the maxillary
      antrum is presented. This case is of interest due because of its extensiveness
      and the presence of a canine tooth in the roof of the maxillary sinus. In
      addition, this caused a right-sided epiphora. Enucleation of the cyst containing
      the ectopic tooth was made.

PMID- 9282205
TI  - Unilateral abducens nerve palsy: a presenting sign of sphenoid sinus mucocoeles.
AB  - Sphenoid sinus mucocoeles can stimulate a variety of pathological conditions and
      patients can present to a range of specialists. Because of the relative rarity of
      sphenoid sinus mucocoeles, diagnosis is often delayed and these lesions can
      progressively expand and cause direct mechanical compression on adjacent
      structures. We present three cases which presented with an abducens nerve palsy.
      Early surgical intervention is advocated and these patients' symptoms resolved
      following surgery. Although several conditions can present with an abducens nerve
      palsy, it is important to consider a sphenoid sinus mucocoele in the differential
      diagnosis.

PMID- 9282206
TI  - Metastatic follicular thyroid carcinoma to the paranasal sinuses: a case report
      and review.
AB  - Thyroid carcinoma metastatic to the paranasal sinuses is extremely rare, with
      only 11 cases reported in the English and European literature. We report a case
      of metastatic follicular thyroid carcinoma to the clivus with extension into the
      sphenoid and posterior ethmoid sinuses. Pathological diagnosis was obtained using
      an intranasal endoscopic biopsy. As with our patient, metastatic thyroid
      carcinoma may present with symptoms related to distant metastases rather than the
      primary lesion. Distant metastases in differentiated thyroid carcinoma portends a
      poor prognosis. Our case of metastatic thyroid carcinoma to the paranasal sinuses
      is summarized in the context of the 11 additional cases, and treatment options
      are discussed.

PMID- 9282207
TI  - Laryngeal foreign body: an unusual complication of percutaneous tracheostomy.
AB  - Impaction of a foreign body in the larynx is a serious event. While inhaled
      foreign bodies may occasionally impact in the larynx especially in children, a
      laryngeal foreign body as a complication of percutaneous tracheostomy has not
      been reported in the literature. We describe the case of a fragment of a
      Seldinger wire retained in the larynx for two years following a percutaneous
      tracheostomy and review the literature on the complications of this procedure.

PMID- 9282208
TI  - Multiple cutaneous metastases from laryngeal carcinoma.
AB  - A case of laryngeal squamous cell carcinoma recurrence presenting as multiple
      cutaneous metastases is presented. Such metastases are rare and are associated
      with a poor prognosis. Treatment is usually aimed at providing pain relief in
      these patients with a limited life expectancy.

PMID- 9282209
TI  - Pharyngeal lipoma with cartilaginous metaplasia (chondrolipoma): a case report
      and literature review.
AB  - The relative rarity of pharyngeal lipomas and paucity of clinical manifestations
      in the early stages of tumour growth conspire to task the diagnostic acumen of
      the clinician. A high index of suspicion and meticulous examination are essential
      in order to arrive at the diagnosis, which may be achieved pre-operatively by
      computerized axial tomography, revealing a mass lesion with a characteristic low
      attenuation value. A case of pharyngeal chondrolipoma in a 25-year-old male is
      reported. It is suggested that this conceptually intriguing and rarely
      encountered lesion can be explained on the basis of neoplastic transformation of
      the second to fourth pharyngeal cleft mesenchymal rests displaying both adipose
      and cartilaginous differentiation. Alternatively, the cartilage could represent
      vestigial remnants of non-neoplastic pharyngeal cleft tissue entrapped within a
      primarily lipomatous neoplasm. Slow growth may occur over a period of several
      years, prior to overt clinical manifestation.

PMID- 9282210
TI  - Tracheoesophageal speech following transmucosal pharyngeal myotomy with the
      potassium-titanyl-phosphate laser.
AB  - Successful communication following laryngectomy usually involves an electrolarynx
      or oesophageal speech. Only within the past decade has tracheoesophageal puncture
      been advocated for alaryngeal speech and evolved into the procedure of choice.
      Successful production of speech after total laryngectomy using tracheoesophageal
      speech may be impaired secondary to anatomical and functional difficulties. The
      primary limitation of tracheoesophageal speech is pharyngoesophageal spasm
      occurring in the upper oesophageal sphincter impeding airflow through this
      segment. Our report presents four patients who underwent a pharyngeal myotomy
      with the potassium-titanyl-phosphate (KTP) laser. Post-operatively, each patient
      was able to communicate with functional alaryngeal speech. A transmucosal
      pharyngeal myotomy may represent an alternative for patients with speech failure
      after tracheoesophageal puncture.

PMID- 9282211
TI  - Posterior tracheal wall diverticula-an unexpected finding.
AB  - Two cases of asymptomatic posterior tracheal wall diverticula, one single and one
      multiple, found unexpectedly at laryngectomy are described. The embryonal
      development and pathogenesis of tracheal abnormalities are discussed, and
      possible clinical implications speculated upon.

PMID- 9282212
TI  - Lateral neck abscess caused by Streptococcus bovis in a patient with undiagnosed
      colon cancer.
AB  - Bacteraemia or endocarditis caused by Streptococcus bovis, a non-enterococcal
      group D streptococcus, is a very common finding in patients suffering from
      intestinal tumours or other colon diseases. A case of a patient with a laternal
      neck abscess caused by S. bovis is reported. During the treatment the patient was
      found to have colonic malignant lesions. The problems in the appropriate
      diagnosis and the possible correlation between these two clinical entities are
      presented and discussed.

PMID- 9282213
TI  - Infantile (desmoid-type) fibromatosis of the parotid gland.
AB  - Infantile fibromatosis, one of the fibrous tumours of infancy and childhood, is a
      fibroproliferative lesion characterized by aggressive local invasion without any
      tendency to metastasize, the absence of cytological evidence of malignancy and a
      high rate of local recurrence when incompletely excised. We report a case of
      infantile (desmoid-type) fibomatosis in a seven-year-old girl arising from the
      deep lobe of the parotid gland that was treated by complete surgical excision
      with preservation of the facial nerve. The clinical features, pathology and
      treatment are briefly discussed.

PMID- 9282214
TI  - Oncocytoma of the nasal cavity: report of a case and review of the literature.
AB  - The authors present a case of oncocytoma of the nasal cavity in a 60-year-old
      woman. The tumour shows the same histological and ultrastructural characteristics
      of oncocytomas arising in minor salivary glands of other sites and major salivary
      glands. The authors stress that the biological behaviour of oncocytomas of the
      nasal cavity seems related to their local growth rather than to the cytological
      characteristics of the tumour. The extreme rarity of this tumour in the nasal
      cavity is particularly emphasized. The few cases reported previously in
      literature are briefly reviewed.

PMID- 9282215
TI  - Microcystic adnexal carcinoma.
AB  - Microcystic adnexal carcinoma (MAC) is a rare adnexal tumour which has only
      recently been recognized as a separate clinicopathological entity. It typically
      affects the face of the middle-aged and often requires extensive surgical
      excision, due to its locally invasive nature. Its clinical significance is that,
      despite being locally invasive, MAC is typified by a lack of metastatic spread.
      We present a case and review of the literature.

PMID- 9282216
TI  - Hemifacial spasm associated with external carotid artery compression of the
      facial nerve.

PMID- 9282217
TI  - Abductor vocal fold palsy in the Shy-Drager syndrome presenting with snoring and
      sleep apnoea.

PMID- 9282218
TI  - Illusory recall of vocal affect.
AB  - Illusions of memory occur when a person recalls something that did not take
      place, and may result from processes that systematically bias recall. This paper
      reports three experiments exploring a novel form of memory bias that can occur
      when a person is attempting to recall the affective tone of voice in which
      someone spoke previously. Subjects first studied photographs of faces while
      listening to sentences spoken in a positive or negative tone of voice. At test,
      subjects saw brief presentations of faces and were asked to recall the tone of
      voice in which the pictured person had spoken earlier. Across a variety of study
      and test conditions a strong recall bias was observed: when faces conveyed either
      subtle positive or negative affect, subjects tended to recall the pictured person
      as having spoken with a matching affective tone, regardless of the tone of voice
      in which the person had actually spoken. It is proposed that this affective
      recall bias may be the product of a retrieval mechanism that relies on a
      combination of information from the memory trace and retrieval environment to
      guide responding.

PMID- 9282219
TI  - The effect of item and relational processing on incidental long-term memory for
      order.
AB  - Although stimulus similarity and levels of processing are often manipulated in
      long-term episodic tasks that test item memory, little attention has been paid to
      how these variable affect long-term memory for temporal order. The effects of
      these variables on order memory was tested using a task that required the
      reconstruction of the initial presentation order of short lists after a filled
      delay. Initial learning of the lists always involved incidental processing
      procedures ranging from low-level item processes to high-level relational
      processes. In all experiments, changes in stimulus similarity and processing
      tasks had similar effects on order memory to the effects found in tasks involving
      long-term item memory. An interpretation of the data is proposed, based on the
      joint contribution of distinctive item and relation processing, and poor encoding
      of order information with shallow processing. It is concluded that item
      information must play a significant role in the long-term order reconstruction
      task.

PMID- 9282220
TI  - What brings intentions to mind? An in situ study of prospective memory.
AB  - In a naturalistic study, we aimed to uncover the relationship between thinking
      about and remembering intentions. Electronic badges allowed us to track the
      activities of subjects within their work environment. Over two weeks, subjects
      were asked to respond using a button on their badges (1) every two hours (Time
      task); (2) whenever they were in a particular room (Place task). In addition,
      whenever they thought about the task, they were asked to indicate this with their
      badges. Although subjects thought about the Time task more, they forgot to
      respond more often than in the Place task. In the Time task, there was a marked
      absence of thoughts about the task following successful remembering. When
      subjects remembered the Place task, thoughts increased with proximity to the
      target location. In both tasks, thoughts about intentions occurred more in places
      such as stairwells than in locations where people tended to settle. On the basis
      of these findings, possible mechanisms for prospective memory are discussed.

PMID- 9282221
TI  - Indexing events in memory: evidence for index dominance.
AB  - Research on narrative comprehension and autobiographical memory converge on three
      hypotheses which make different predictions about event organisation. The
      availability of different event components as indexes may explain the convergence
      on three hypotheses rather than one. In this paper, three experiments assessed
      event indexing in narratives with different available indexes. In Experiment 1,
      participants read event descriptions organised by character or time. In
      Experiment 2, event descriptions were organised by character or location. In
      Experiment 3, participants read event descriptions where events were grouped by
      activity. In each experiment, memory could be organised by any of the available
      components alone, by both components, or by using the organisation imposed by the
      discourse. Participants indexed events by character in Experiment 1, re-indexing
      information when necessary. Results of Experiment 2 indicated equal use of
      character and location indexes. In this case, participants used the discourse
      organisation. In Experiment 3, participants indexed events using activity
      groupings, again re-indexing events when necessary. Results are interpreted as
      indicating reliance on a single organising index with flexibility in the
      selection of different event components as indexes.

PMID- 9282222
TI  - Brains of ants and elephants.

PMID- 9282223
TI  - Glass patterns: some contrast effects re-evaluated.
AB  - The relative contrast of features is known to be important in determining if they
      can be grouped. Two manipulations of feature contrast have previously been used
      to criticise models of visual grouping based on spatial filtering: high-pass
      filtering and reversal of contrast polarity. The effects of these manipulations
      are considered in the context of the perception of Glass patterns. It is shown
      that high-pass filtering elements, whilst destroying structure in the output of
      low-pass filters, do not significantly disrupt the output of locally band-pass
      filters. The finding that subjects can perceive structure in Glass patterns
      composed of high-pass features therefore offers no evidence against such spatial
      filtering mechanisms. Band-pass filtering models are shown to explain the
      rotation of perceived structure in Glass patterns composed of opposite contrast
      features. However, structure is correctly perceived in patterns composed of two
      'interleaved' opposite contrast patterns, which is problematic for oriented
      filtering mechanisms. Two possible explanations are considered: nonlinear
      contrast transduction prior to filtering, and integration of local orientation
      estimates from first-order and second-order mechanisms.

PMID- 9282224
TI  - Can illusory motion disrupt tracking real motion?
AB  - When rotating stripes or other periodic stimuli cross the retina at a critical
      rate, a reversal in the direction of motion of the stimuli is often seen. This
      illusion of motion perception was used to explore the roles of retinal and
      perceived motion in the generation of optokinetic nystagmus. Here we show that
      optokinetic nystagmus is disrupted during the perception of this illusion. Thus,
      when perceived and actual motion are in conflict, subjects fail to track the
      veridical movement. This observation suggests that the perception of motion can
      directly influence optokinetic nystagmus, even in the presence of a moving
      retinal image. A conflict in the neural representation of motion in different
      brain areas may explain these findings.

PMID- 9282225
TI  - Suppressive effect of multimodal surface representation on ocular smooth pursuit
      of invisible hand.
AB  - A human observer can smoothly pursue her/his own voluntarily moved hand with the
      eyes in total darkness. The effects of a perceived stationary surface during
      ocular pursuit of the invisible hand were investigated. The task was to track the
      invisible hand smoothly with the eyes in a Ganzfeld (experiment 1), with a
      stationary visual surface in the light (experiment 2), or with a solid stationary
      surface in total darkness (experiment 3). It was found that smooth pursuit of the
      invisible hand occurred in the Ganzfeld as well as in total darkness, but was
      replaced by frequent saccades when a stationary surface was perceived through
      either the visual or the tactile sense. The results obtained with a Ganzfeld
      suggest that light alone does not prevent smooth pursuit of the invisible hand,
      and those obtained with a stationary surface suggest that perception of such a
      surface prevents smooth pursuit of the invisible hand and evokes saccades,
      regardless of the sense modality.

PMID- 9282226
TI  - Effect of size and frame of visual field on the accuracy of an aiming movement.
AB  - The aim of this study was to analyse the effects of manipulating the size and
      contour of the visual field on the accuracy of an aiming task. Subjects were
      required to perform pointing movements without seeing their moving hand. The
      target was displayed in either a wide structured visual field (control
      condition), a narrow visual field with orthogonal frame, or a narrow visual field
      with circular frame. The visual information surrounding the target was always
      provided prior to movement onset, but during the execution of the movement on
      only half of the trials. Overall, the results showed that undershooting was a
      common performance characteristic in all of the conditions. In comparison to the
      control performance, an increase of the degree of undershoot was found when the
      target was displayed inside a narrower visual field. An additional radial error
      was found when the contour of the visual scene was circular, but only when the
      visual context was available during the movement. The same pattern of results was
      observed for variable error. However, angular errors were not found to vary over
      the different conditions. Overall, the findings suggested that the visual context
      contributed to the assessment of the target locations, and the subsequent motor
      programming. Furthermore, visual information aided the on-line control of the
      unseen hand, but the extent of this was dependent on the size and shape of the
      frame denoting the visual scene. Finally, in the absence of any unexpected
      perturbation, the en-route amendment of the arm trajectory, based on visual
      information processing, seemed to be more related to distance than azimuth
      control.

PMID- 9282227
TI  - Homing in virtual environments: effects of field of view and path layout.
AB  - Triangle completion (ie homing to the starting point after completing two legs of
      a triangle) is a widely used method for examining path-integration abilities in
      animals and humans. Two experiments are reported in which homing was used to
      examine the efficiency of purely visual mechanisms (eg optical flow) for spatial
      information coding and integration. Adult observers had to complete triangles in
      an interactively simulated three-dimensional environment which consisted of two
      critical objects and a homogeneous set of white cylinders serving as background.
      Each participant completed twenty-seven triangles corresponding to a factorial
      combination of three geometrical fields of view (40 degrees, 60 degrees, or 80
      degrees) and nine triangle layouts (with variations of the first turning angle
      and the second leg). Homing performances revealed strong effects of triangle
      layout, but no effect of geometrical fields of view: variations in the amount of
      simultaneous visible spatial information did not influence the acquisition of
      spatial knowledge in the environments used. Applying the encoding-error model to
      the data revealed severe systematic errors of picking up directional information
      while moving through visually simulated environments. These results are discussed
      with respect to informational differences between situations of purely visual and
      nonvisual navigations in space.

PMID- 9282228
TI  - Large scale differences between haptic and visual judgments of curvature.
AB  - Large systematic scale differences show up when subjects are asked to match the
      curvature of a haptically presented surface with a visually presented cross
      section. Scaling factors ranging from 0.3 to 3.0 were found. Most often (for five
      out of six subjects) haptically estimated curvature was overestimated relative to
      visual curvature. We conclude that mutually inconsistent representations of
      surface curvature coexist in a single observer in the haptic and visual
      modalities. Another conclusion can be drawn with certainty, namely that at least
      one of the two modalities does not provide the observer with veridical
      information. The results for the left and the right hand of a subject were very
      similar, though for two subjects there existed a small significant difference in
      scaling. It seems likely that the curvature representations of the two hands are
      not independent of one another, but our data do not permit us to be conclusive.

PMID- 9282229
TI  - Global precedence in visual search? Not so fast: evidence instead for an oblique
      effect.
AB  - The evidence from an earlier report of global precedence in visual search is
      reexamined. Two new experiments are reported. The results of the first experiment
      indicate that the confusability of oblique orientations (a class-2 oblique
      effect) rather than global precedence was responsible for the earlier results.
      The results of the second experiment show that the effect critically depends on
      the presence of heterogeneous distractors rather than on differences in raw
      processing speed for different spatial scales. The possible role of symmetry is
      discussed.

PMID- 9282230
TI  - Preschoolers' perception of other people's looking: photographs and drawings.
AB  - Children aged 3-4 years were tested for their ability to decide which of two
      photographs or drawings of a face depicted the act of fixating on a target
      object; in each control photograph or drawing the same face and object were
      present without fixation. Performance was above chance on both stimulus types,
      but low enough to call into question conclusions from previous research. The same
      children were also tested on their ability to discriminate between
      photographs/drawings depicting two faces fixating the same object (joint visual
      attention) and the same two faces fixating different objects. While
      discrimination of joint visual attention depicted in drawings was as good as
      discrimination of fixation in the single-face tasks, the ability to reliably
      choose between a photograph of two people attending to a common object and a
      control photograph was significantly poorer. The results suggest that, while
      young infants and children may be highly sensitive to face-on gaze, even well
      into the fourth year of life children are unable consistently to interpret (1)
      direction of non-self-directed gaze in static faces and (2) joint visual
      attention by others.

PMID- 9282231
TI  - Early-blind subjects' spatial representation of manipulatory space: exploratory
      strategies and reaction to change.
AB  - The present study was aimed at analysing the effects of a lack of visual
      experience in human subjects on the detection and identification of a spatial
      change brought about to a configuration of objects displayed in manipulatory
      space. Exploratory patterns and performance levels were recorded. Learning
      effects were observed in different types of change and condition of presentation
      only in the early-blind and blindfolded sighted groups, but not in the late-blind
      group. Early blindness affected both exploratory patterns and performance levels.
      In addition, significant correlations were found between performance level and
      the use of systematic patterns of exploration. These data are discussed in
      relation with the importance of early vision during the development of spatial
      cognition.

PMID- 9282232
TI  - Note: half-a-million basic colour words: Berlin and Kay and the usage of colour
      words in literature and science.
AB  - Berlin and Kay have proposed that the order of evolution of colour words is
      highly conserved across languages. Previously I have suggested that the same
      order of colour words, with black, white, and red first, and pink, purple,
      orange, and grey last, is found in the rate of usage of colour words within
      languages. That hypothesis is now further supported by the frequencies of the
      eleven English basic colour words in 507,256 cases in eight large computerised
      data bases, there being a rank correlation of 0.802 with the Berlin and Kay
      order.

PMID- 9282233
TI  - Inflammatory changes in proximal and peripheral airways of asthmatic patients.

PMID- 9282234
TI  - Effects of high-dose ipratropium bromide and oral aminophylline on spirometry and
      exercise tolerance in COPD.
AB  - Exercise tolerance in chronic obstructive pulmonary disease (COPD) patients
      treated with oral aminophylline may be different from those treated with high
      dose inhaled ipratropium bromide. The purpose of this study was to compare the
      effects of therapeutic doses of oral aminophylline with high-dose ipratropium
      bromide on spirometry and exercise tolerance. The study was conducted on three
      consecutive days in a double-blind, randomized, crossover fashion. Baseline
      studies obtained on each study day included vital signs, simple spirometry and a
      symptom-limited maximal cardiopulmonary stress test, after which patients
      received one of the following treatments on each day: Treatment 1, inhaled
      ipratropium (total dose of 144 micrograms) with placebo tablets; Treatment 2,
      inhaled placebo with oral aminophylline (400 mg); Treatment 3, inhaled placebo
      and placebo tablets. Simple spirometry was repeated at 60 and 120 min after
      baseline. Vital signs and cardiopulmonary stress testing was repeated at 120 min.
      Eighteen patients were enrolled in the study, and 17 of these completed the
      study. There was a significant (P < 0.05) increase in both forced expiratory
      volume in 1 s (FEV1), from 0.75 (0.21) to 0.92 (0.3), and forced vital capacity
      (FVC), from 1.8 (0.79) to 2.11 (0.84), with high-dose ipratropium despite prior
      beta-agonist therapy. Lack of improvement in exercise capacity was noted with
      ipratropium despite improvement in spirometry. These results suggest that elderly
      patients with severe COPD may have exercise limitation that is not directly
      dependent on severity of airflow obstruction. Ipratropium bromide and
      aminophylline demonstrated no acute effects on exercise capacity.

PMID- 9282235
TI  - Lack of effect of nitric oxide inhibition on bronchial tone and methacholine
      induced bronchoconstriction in man.
AB  - The role of nitric oxide (NO) as a bronchodilator has been studied in humans with
      controversial results. The aim of the present study was to investigate the role
      of endogenous NO on bronchial tone by studying whether nitric oxide synthase
      (NOS) inhibition with NGnitro-L-arginine-methyl-ester (L-NAME) influences basal
      bronchial tone, or potentiates methacholine-induced bronchoconstriction. In a
      preliminary experiment in five subjects, a significant reduction in exhaled NO
      was found after delivering L-NAME (15 mg in saline) (from 3.9 +/- 1.2 to 2.4 +/-
      1.1 nmol min-1, P < 0.05). In nine healthy non-smokers, specific airway
      conductance (SGAW), as a measure of airway calibre, was recorded after
      delivering, in a double-blind, controlled vs. placebo fashion, both nebulized L
      NAME and saline, at baseline and after methacholine-induced bronchoconstriction.
      There was no significant difference between the baseline SGAW values before and
      after delivering L-NAME (0.264 +/- 0.04 and 0.267 +/- 0.05 cm H2O-1 s-1,
      respectively). After pre-treatment with L-NAME, SGAW values during methacholine
      induced bronchoconstriction were not different in comparison to values obtained
      after saline inhalation. It is concluded that decreased endogenous NO does not
      influence bronchial tone in healthy people, nor does it modify methacholine
      induced bronchoconstriction.

PMID- 9282236
TI  - Influence of inspiratory capacity on bronchodilatation via Turbuhaler or
      pressurized metered-dose inhaler in asthmatic children: a comparison.
AB  - This study was designed to compare the bronchodilatatory effect of terbutaline
      inhaled through Turbuhaler (TH) or pressurized metered-dose inhaler (pMDI) in
      young asthmatics, and to assess the possible relationship between patients'
      inspiratory capacity and bronchodilatation for both devices. One hundred and
      eighteen asthmatics (aged 4 10/12-20 6/12 years) with bronchial obstruction (mean
      Vmax 50%: 59.5% pred, SD 17.8% pred) were allocated at random to two groups of 59
      patients to inhale 0.5 mg terbutaline either by TH or by pMDI (and placebo by
      dummy of the other device). In- and expiratory spirometry and bodyplethysmography
      were conducted before and 10 min after inhalation. Bronchodilatation was
      effective [change in airways resistance (delta RAW) -50%, change in forced
      expiratory volume in 1 s (delta FEV1)+15%, delta Vmax 50% or 25% + 25% of
      baseline] in 41 of 59 patients with pMDI (69.5%) and 33 of 59 patients with TH
      (55.9%). The effect on Vmax 50% was significantly better with pMDI than with TH.
      Turbuhaler users with higher inspiratory flow [forced inspiratory volume in 1 s
      (FIV1), forced inspiratory flow at 50% vital capacity (FIF50)] reached better
      bronchodilatation, while bronchodilatatory effect was not correlated with
      inspiratory performance in MDI users. Peak inspiratory flow (PIF) did not
      correlate well with bronchodilatation by TH. When using TH for bronchodilatation,
      the effectiveness of terbutaline depends upon the degree of inspiratory capacity.
      This can lead to impaired bronchodilatatory effect in subgroups of obstructive
      young asthmatics with low inspiratory flow. In contrast, when using a pMDI,
      inspiratory capacity does not seem to influence the effectiveness of terbutaline.

PMID- 9282237
TI  - Seasonal variation in serum eosinophilic cationic protein (S-ECP) in a general
      population sample.
AB  - The aim of this investigation was to study the seasonal variation in the serum
      levels of eosinophil cationic protein (S-ECP). The study population comprised a
      general population sample of 379 individuals (range: 20-45 years) who were
      investigated with blood sample for the measurement of S-ECP, skin prick test and
      methacholine challenge. The examination took place between May and October 1991.
      Of the 379 subjects investigated, 137 (36%) were atopic. A significant seasonal
      variation in S-ECP was found in the group of birch-pollen-positive subjects (P <
      0.05), but not in the non-atopic or birch-negative atopic group. The mean level
      of S-ECP in birch-positive subjects was about twice as high in June as in birch
      atopic subjects examined during other months. It is concluded that seasonal
      variation in birch-pollen-positive subjects must be taken into account when using
      S-ECP clinically or in epidemiological research.

PMID- 9282238
TI  - Pulmonary microvascular injury following general anaesthesia with volatile
      anaesthetics--halothane and isoflurane: a comparative clinical and experimental
      study.
AB  - Pulmonary microvascular injury has become a recently studied phenomenon that may
      be responsible for most of the complications associated with the lungs. Thirty
      patients undergoing partial hemilaminectomy or discectomy due to hernia of
      nucleus pulposus underwent Tc-99m HMPAO lung clearance as well as Tc-99m
      pertechnetate lung scintigraphy pre-operatively, and following general
      anaesthesia with halothane and isoflurane (third, fourth and tenth post-operative
      days). The results were compared with conventional techniques and haemodynamic
      parameters during the peri-operative period. In order to demonstrate acute phase
      changes under general anaesthesia and to perform pathological examinations, 21
      New Zealand rabbits underwent radionuclide studies with Tc-99m HMPAO or Tc-99m
      pertechnetate. Lung biopsies were also performed. Despite no significant
      differences in any of the conventional diagnostic techniques, Tc-99m
      pertechnetate lung scintigraphy was performed for both the halothane and
      isoflurane groups, and Tc-99m HMPAO lung clearance was performed for the
      isoflurane group pre- or post-operatively. Tc-99m HMPAO lung clearance was
      impaired significantly in the halothane group on the third post-operative day
      (half time: 6.4 +/- 1.6 pre-operative and 13.76 +/- 3.3 s, P < 0.001) decreasing
      to pre-operative levels on the tenth post-operative day. Acute phase exposure to
      halothane was characterized with extremely abnormal Tc-99m HMPAO lung clearance
      in rabbits with respect to isoflurane, diminishing to control levels on the third
      day (half time: 8.7 +/- 86 control and 28.65 +/- 4.6, P < 0.001). Pathological
      examinations also demonstrated endothelial damage on acute exposure in the
      halothane group. General anaesthesia with halothane may give rise to alveolar
      microvascular injury, which generally seems to be underdiagnosed and may lead to
      serious post-operative complications.

PMID- 9282239
TI  - Evaluation of response to chemotherapy in patients affected with non-small cell
      lung cancer by means of three tumour markers elaborated by discriminant analysis.
AB  - Chemotherapy is the most effective treatment for inoperable patients (70%)
      affected with non-small cell lung cancer (NSCLC). The early detection of tumour
      progression is mandative in order to promptly shift these patients towards
      salvage or supportive therapy. The present authors investigated the clinical
      value of a panel of tumour markers, elaborated by means of discriminant analysis,
      as a follow-up indicator for the detection of tumour progression. The serum
      levels of tissue polypeptide antigen (TPA), CYFRA-21.1, neuron-specific enolase
      (NSE) and carcino-embryonic antigen (CEA) were determined before chemotherapy and
      after three cycles of treatment. Discriminant analysis generated a formula
      (canonic variable) which correctly classified the 87.8% of the 74 subjects (86.1%
      of the 36 progressive diseases and 89.5% of 38 non-progressive diseases). This
      approach produces an algorithm able to calculate a progression score in NSCLC
      patients which can be helpful for following-up care and therapy control of these
      patients.

PMID- 9282240
TI  - Evaluation of a pocket-sized turbine spirometer for clinical use with children.
AB  - The results of pulmonary function testing with a turbine spirometer (TS) and a
      bell spirometer (BS) of a randomized group of 275 patients aged 4-18 years were
      compared. In the TS, an inexpensive device without graphical display was used.
      The difference BS minus TS (d) for forced expiratory volume in 1 s (FEV1) was
      calculated. The results indicate that the FEV1 might be overestimated by the TS,
      and that the difference of the readings of FEV1 between the spirometers increases
      with airway obstruction. The TS should be used with caution in young patients
      with asthma.

PMID- 9282241
TI  - Post-traumatic pleural effusion: demonstration of local complement consumption.
AB  - The present case report describes a 27-year-old patient who presented with post
      traumatic pleural effusion. Analysis of the pleural fluid showed
      hypereosinophilia (990 mm-3), a decreased level of total complement, and
      decreased levels of C3 and C4 fractions (less than 50% of normal serum levels),
      indicating a local consumption mechanism for complement. Complement serum levels
      (CH50, C3, C4) were normal. All other aetiologic possibilities were eliminated.
      This case suggests that the immunopathological mechanism of post-traumatic
      pleural effusion may involve activation of the classical pathway of complement
      and a recruitment of inflammatory cells such as eosinophils.

PMID- 9282243
TI  - Inflammatory pseudotumour of the lung presenting as an airway obstructive
      syndrome.
AB  - The inflammatory pseudotumour of the lung is a rare and non-malignant neoplasm,
      which can be asymptomatic or characterized by variable clinical expressions. This
      report refers to a case occurring in a young woman and presenting as a persistent
      airway obstructive syndrome. With regard to histopathologic characterization, the
      present case can be classified as a fibrous histiocytic subtype.

PMID- 9282242
TI  - A case of rapidly expanding tuberculous lung cavity after bronchoscopy.
AB  - A non-smoking Asian woman with previously treated pulmonary tuberculosis
      presented with a recent onset unproductive cough and cavitating mass lesion on
      her chest X-ray which rapidly developed into a large tuberculous cavity after
      bronchoscopy. Acid-fast bacilli were isolated from the cavity and she responded
      very rapidly to standard anti-tuberculous chemotherapy. This unusual condition
      must be considered in patients who deteriorate after bronchoscopy.

PMID- 9282244
TI  - Vitamin D: an antiproliferative agent with potential for therapy of squamous cell
      carcinoma.

PMID- 9282246
TI  - A method to evaluate upper airway mechanics following intervention in snorers.
AB  - PURPOSE: To describe a method that measures multisegment upper airway changes
      following intervention for snoring and obstructive apnea that controls for
      physiological fluctuations during sleep. PATIENTS AND METHODS: Retropalatal,
      retroglossal, and retrohyoid airway segments were evaluated before and after
      application of an oral appliance (OA) in four snoring subjects. Twelve airway
      segments were evaluated. Physiological fluctuations during sleep were controlled
      with variably applied nasal continuous positive pressure (CPAP), benzodiazepam
      induced sleep, and obtaining measures at zero flow on the first test breath.
      Airway area was measured endoscopically. RESULTS: The methodology identified that
      following intervention with an OA, maximum retroglossal airway size increased
      23.3% +/- 7.5% (P < .05) and retrohyoid size decreased -63.5% +/- 16.0% (P <
      .05). No changes in retropalatal area (-2.5% +/- 3.0%) or closing pressure were
      observed. The level of primary obstruction shifted inferiorly in one patient.
      Airway measures prior to intervention showed small alterations of applied
      pressure (1 cm H2O) changed retropalatal and retroglossal area an average of 10%
      +/- 0.9%/cm H2O. CONCLUSION: The mechanical effects of limited airway
      intervention can be measured with a hypotonic, pressure-controlled methodology.
      At small airway areas, the airway is highly collapsible and airway size
      fluctuates. Small changes in applied or physiological forces may alter the airway
      as significantly as the effects of the intervention being evaluated. The
      hypotonic upper airway method provides a method to control airway collapse and
      evaluate interventions, such as OA or surgery, for snoring and obstructive sleep
      apnea syndrome.

PMID- 9282245
TI  - Conservative management of T1-T2N0 supraglottic cancer: a retrospective study.
AB  - PURPOSE: Evaluate the results of conservative management of early-stage
      supraglottic cancer. PATIENTS AND METHODS: A retrospective analysis of 166
      consecutive T1-T2N0 cases of squamous cell carcinoma of the supraglottic larynx,
      treated conservatively between 1983 and 1992, was performed. Sixty-six patients
      received conservative surgery (CS), whereas 100 patients received definitive
      radiation therapy (RT). Surgical procedures included horizontal supraglottic
      laryngectomy in 38 patients, extended supraglottic laryngectomy in 16 patients,
      and reconstructive laryngectomy with cricohyoidopexy in 12 patients. Elective
      bilateral neck dissection was always performed. Radiotherapy was delivered with
      60Co or 6 MV photons to the primary laryngeal tumor and the upper and mid neck
      nodes (level II and III), whereas supraclavicular nodes (level IV) were
      electively irradiated only in 54 patients with T2N0 tumors. Fifty-two patients
      received conventional fractionation, whereas 31 patients were irradiated
      according to a twice-a-day fractionation regimen. The median total tumor dose was
      67 Gy (range, 64 to 72 Gy). RESULTS: The 5-year overall survival of the whole
      series was 72.7% +/- 4.5. In patients treated with CS, the 5-year disease-free
      survival was 88.4% +/- 4.5 versus 76.4% +/- 6.1 for patients who received RT.
      Salvage surgery was effective in rescuing 2 of 3 CS failures and 12 of 25 RT
      failures. The overall incidence of secondary tumors (11%) and distant metastases
      (5%) was relatively low, although together they account for 15% of all deaths.
      Complications of CS were significantly correlated to the extent of surgical
      procedure. A multivariate analysis performed in the RT group showed that
      performance status, tumor grade, and fractionation regimen significantly
      influenced disease-free survival. CONCLUSION: Conservative management of T1-T2N0
      supraglottic cancer, either by CS or RT, can achieve good cure rates with larynx
      preservation for the majority of the patients (82% overall; 95% in the CS group
      and 72% in the RT group). The decision between different conservative treatment
      modalities may be influenced by the patient's conditions, tumor characteristics,
      treatment modalities, and also economic costs.

PMID- 9282247
TI  - Porcine model of airway mucosal injury.
AB  - PURPOSE: The development of a reliable animal model of laryngeal or tracheal
      stenosis has been limited by lack of reproducibility, high morbidity and
      mortality, and cumbersome technique. The small size of previously proposed models
      has limited the development of innovative reconstructive techniques. MATERIALS
      AND METHODS: Eleven of 15 post-weanling commercial piglets underwent injury by a
      sharpened metal rod to the anterior half of the subglottic region at repeated
      intervals under endoscopic guidance. Four of 15 animals did not undergo injury
      and served as control for normal subglottic growth over time. Each airway was
      sized by endotracheal tube (ETT) passage and endoscopic photography over time,
      and the degree of total stenosis was estimated in comparison to the control
      animals. RESULTS: The first two animals underwent daily injury and expired from
      copious granulation tissue. Eight additional animals developed symptomatic
      subglottic stenosis manifested by audible stridor and intercostal retractions
      while undergoing injury every third day. Photographs documented the size of the
      stenosis to be greater than 50% (40% by ETT sizing) with a mean of three injuries
      in a mean time of 18 days. CONCLUSION: The porcine model shows a high degree of
      tolerance with minimal morbidity and consistent reliable results in an animal
      model of airway stenosis that is suitable for further innovative studies.

PMID- 9282249
TI  - Risk factors for otitis media with effusion in children 0 to 2 years of age.
AB  - PURPOSE: To determine the possible risk factors associated with the occurrence of
      otitis media with effusion. PATIENTS AND METHODS: Two hundred eighty-nine
      children born between July 1987 and October 1988 were studied up to the age of 24
      months. The enrollment of the children took place during their regular check-up
      visits at three different health-care centers. RESULTS: Having older sibling was
      the most important risk factor, for both the time elapsed until the first
      occurrence and for the probability of otitis media with effusion at each visit.
      Other significant risk factors for the probability at each visit were: having had
      acute otitis media before the visit or before the previous visit, age, a positive
      family history of otitis media, and upper respiratory tract infections (URTI).
      CONCLUSION: Having older siblings is the most important risk factor for otitis
      media with effusion in this age group.

PMID- 9282250
TI  - Submandibular malignant myoepithelioma.

PMID- 9282248
TI  - Lyme disease and seventh nerve paralysis in children.
AB  - PURPOSE: This study was undertaken to determine the frequency of Lyme disease
      (LD) as a cause of transient facial nerve palsy (FNP) in children. Acute onset
      FNP in children has been primarily associated with acute otitis media (AOM).
      Recently, LD has emerged in regions where the deer-tick vector is present and has
      been associated with multiple cranial neuropathies. PATIENTS AND METHODS: Fifty
      children with transient FNP were evaluated and treated at our institution over a
      5.5-year period. RESULTS: The rank of etiologies confirmed LD to now be the most
      common (50%), followed by AOM (12%), varicella (6%), Herpes zoster (4%), and
      coxsackievirus (2%). Thirteen children (26%) had idiopathic FNP consistent with
      Bell's palsy. CONCLUSION: We conclude that transient FNP in children is most
      commonly caused by LD for regions with endemic infections caused by Borrelia
      burgdorferi.

PMID- 9282251
TI  - Extraction of a large tracheal foreign body through a tracheotomy.

PMID- 9282252
TI  - Carotid artery hemorrhage resulting from temporal bone fracture.

PMID- 9282253
TI  - Endoscopic resection of a recurrent sinonasal hemangiopericytoma.

PMID- 9282254
TI  - Idiopathic central vocal fold adhesion.

PMID- 9282255
TI  - Temporal bone histopathology of Niemann-Pick disease type A.

PMID- 9282257
TI  - Effect of cadmium on antioxidant status in alloxane-induced diabetic rats.
AB  - Fifty-two healthy Swiss Male Albino rats aged two mo were used in this study.
      They were divided into four groups: control (C), diabetic (D), cadmium (Cd), and
      diabetic + Cd (D + Cd) groups. Diabetic condition was induced in D and D + Cd
      groups by administration of alloxane (5 mg/100 g). After this treatment, Cd and D
      + Cd groups were injected with CdCl2 i.p. (2 mg/kg/wk). At the end of the 2-mo
      experimental period, thiobarbituric acid reactive substances (TBARS), plasma and
      erythrocyte selenium (Se), plasma ceruloplasmin (Cp), and vitamin E (vit E) were
      determined in four groups of rats. The erythrocyte Se was lower in the
      experimental groups than in the controls. Plasma Se was significantly decreased
      in the D and D + Cd groups compared with the control group. Plasma Cp was
      unaltered. Plasma vit E was significantly decreased in Cd group in comparison
      with the C, D, and D+Cd groups.

PMID- 9282258
TI  - Erythrocyte metallothionein in relation to other biochemical zinc indices in
      pregnant and nonpregnant women.
AB  - Erythrocyte metallothionein (E-MT) is considered a promising index of zinc status
      in humans, since it may be more sensitive than other biochemical indices to
      changes in dietary zinc. However, conditions of high zinc demand with substantial
      redistribution of tissue zinc and specific changes in hormone profile, such as
      pregnancy, may have an influence on E-MT levels in addition to dietary zinc. In
      this study, we compared E-MT concentrations in relation to other biochemical zinc
      indices in healthy pregnant women at delivery (n = 40) and non-pregnant women (n
      = 22) with similar habitual dietary zinc intakes (average 13.3 mg/d). Pregnant
      women had lower serum zinc and albumin-bound serum zinc, but higher levels of
      alpha 2-macroglobulin-bound serum zinc than the nonpregnant women. Erythrocyte
      zinc (E-Zn) was similar in both groups, but E-MT (mean +/- SE) was slightly but
      significantly (p < 0.05) higher in the pregnant women (2.9 +/- 0.09 nmol/g
      protein) compared to nonpregnant women (2.6 +/- 0.06 nmol/g protein). A
      significant correlation was observed between E-MT and E-Zn in the nonpregnant
      women (r = 0.70; p < 0.001), consistent with the role of intracellular zinc in
      the regulation of metallothionein synthesis. However, such correlation was not
      observed in the pregnant women, suggesting that E-MT levels in pregnancy may be
      influenced by factors related to the pregnant state.

PMID- 9282256
TI  - Unchanged iron and copper and increased zinc in the blood of obese children after
      two hypocaloric diets.
AB  - Serum iron (sFe), and ferritin (sFert), transferrin saturation index (TSI),
      plasma zinc and copper (pZn, pCu), and erythrocyte zinc content (eZn) were
      measured in 55 obese children and adolescents (28 males and 27 females) before
      and after a 13-wk treatment with a hypocaloric balanced diet (HCBD, 22 subjects)
      or a 10-wk treatment with a protein sparing modified fast diet (PSMF, 33
      subjects). The energy intake provided by the HCBD and PSMF diet was calculated to
      be 60 and 25%, respectively, of the recommended dietary allowances (RDAs) for age
      and sex. Neither diet was supplemented with trace elements or calcium. Using a
      visual memory system, all subjects had a 24-h dietary intake recall before
      starting the weight-loss program. Iron, zinc, and copper intakes from the 24-h
      recall were compared with those from prescribed diets. Both diets produced a
      significant (p < 0.001) weight reduction with a significant reduction in the arm
      muscle area of the PSMF group. After treatment, no significant change was
      observed in sFe, sFert, and TSI of either group, whereas eZn increased
      significantly in the HCBD and the PSMF groups (p = 0.001 and p < 0.006,
      respectively), with an improvement of the erythrocyte index (E.I.). A significant
      increase in pZn was also observed in the PSMF group (p = 0.007).

PMID- 9282260
TI  - Calcium, magnesium, and zinc status in experimental hyperthyroidism.
AB  - In this study, experimental hyperthyroidism was established and used to
      investigate possible alterations in the calcium (Ca), magnesium (Mg), and zinc
      (Zn) homeostasis by assessing their concentrations in plasma and erythrocytes. In
      the L-thyroxine-induced hyperthyroidism condition, the experimental animals show
      a significant decrease in erythrocyte Ca, Mg, and Zn concentrations, and a
      significant decrease in plasma Mg concentration. Significant positive
      correlations were found for Mg and Zn both in plasma and in erythrocytes. The
      results suggest that the homeostasis of Ca, Mg, and Zn is altered during
      experimental hyperthyroidism.

PMID- 9282259
TI  - Oral aluminum administration and oxidative injury.
AB  - For a long time, aluminium (Al) has been considered an indifferent element from a
      toxicological point of view. In recent years, however, Al has been implicated in
      the pathogenesis of several clinical disorders, such as dialysis dementia, the
      fulminant neurological disorder that can develop in patients on renal dialysis.
      In the present study, the effect of chronic oral administration of Al on certain
      biochemical parameters of brain homogenate has been investigated. The feeding of
      test diet for 6 wk resulted in a decrease of thiols, glutathione reductase (GR),
      and adenosine Triphosphatase (ATPase). A nonsignificant decrease in peroxidation
      and glutathione-S-transferase (GST) was also detected in the Al-treated rats.
      From this study, it can be concluded that oxidative stress is produced by the
      metal.

PMID- 9282261
TI  - Zinc attenuation of GDP binding to brown adipocytes mitochondria in genetically
      obese (ob/ob) mice.
AB  - In this study, we investigate the in vitro effect of zinc addition on guanosine
      diphosphate (GDP) binding to mitochondria in brown adipocytes of genetically
      obese (ob/ob) mice. Interscapular brown adipocytes of male mice (obese; lean) at
      4 and 12 wk of age were incubated with 0, 50, 100, or 200 microM zinc sulfate.
      Mitochondria were then isolated and their GDP binding capacities were measured.
      The GDP-binding capacities of ob/ob mice were lower than lean mice, with or
      without zinc addition, in both age groups (p < 0.05). Zinc addition did not have
      any significant effect on GDP binding in lean mice. GDP binding decreased with
      increasing zinc addition in ob/ob mice, and this attenuation was more predominant
      in 12-wk old ob/ob mice. Moreover, we found that high magnesium addition (5 mM)
      increased GDP binding in lean mice, but this effect was not significant in ob/ob
      mice. This study reveals that brown adipose tissue thermogenesis in ob/ob mice
      could be greatly attenuated by zinc addition, suggesting that zinc may play a
      regulatory role in obesity.

PMID- 9282262
TI  - The decrement of carcinogenesis by dietary selenium and expression of placental
      form of glutathione-S-transferase in rat glioma.
AB  - Supranutrition dietary levels of the element selenium (Se) that have been shown
      to reduce or retard tumor development resulting from transplantation. The rat
      placental form of glutathione-S-transferase (GST-p) has been reported to be a
      good marker for pre-neoplastic or neoplastic lesions. Four groups of rats with
      glioma were exposed to Se-free, 0.05, 2.0, and 4.0 ppm sodium selenite GST-p was
      investigated. Normal brain tissue did not differ significantly in all groups. In
      contrast, GST-p in tumor was significantly higher in Se-free and 4.0-ppm groups
      compared to 0.5- and 2.0-ppm groups. The concentration of Se in normal brain
      tissue did not differ significantly in Se-supplement groups. By contrast, Se in
      tumors was significantly higher in the 0.5- and 2.0-ppm groups compared to the Se
      free and 4.0-ppm groups. Mean group survival at 30 d after treatment was
      determined and compared with previous dietary Se. Survival was significantly
      longer in the 0.5- and 2.0-ppm groups than in the Se-free and 4.0-ppm groups. The
      2.0-ppm group had enhanced survival, similar to the 0.5-ppm group. The Se-free
      and 4.0-ppm groups might have no protection against carcinogenesis.

PMID- 9282263
TI  - Influence of selenium deficiency on the acute cardiotoxicity of adriamycin in
      rats.
AB  - The influence of selenium (Se) deficiency on the acute cardiotoxicity induced by
      the anticancer drug adriamycin (ADR) has been studied in rats by
      electrocardiography. Two categories were formed by feeding groups of rats a Se
      supplemented and a Se-deficient diet. The supplemented animals were taken as
      normals. The two categories were treated with iv injections of saline solution
      containing ADR at doses of 0, 7.5, and 15 mg/kg body wt. The cardiac Se
      concentration and glutathione peroxidase (GSH-Px) activity in the Se-deficient
      groups were < 2% lower than in the normals. The normal groups showed significant
      widening of the SaT and QaT durations when given 15 mg/kg ADR. The Se-deficient
      groups exhibited a dose-dependent widening of the SaT and QaT duration at 7.5 and
      15 mg/kg and narrowing of the PQ duration at 15 mg/kg ADR. No heart rate or QRS
      duration changes were detected in both categories. Our results suggest that an
      imbalance of the antioxidant system is associated with Se deficiency and that Se
      plays a role in preventing the cardiac functional disorder attributable to oxygen
      free radical formation induced by ADR.

PMID- 9282264
TI  - Water metabolic parameter changes in rhesus monkeys during exposure to prolonged
      restriction of motor activity.
AB  - The objective of this investigation was to determine the effect of prolonged
      restriction of motor activity (hypokinesia [HK]) on several parameters of water
      metabolism in primates. The studies were performed on 12 rhesus monkeys aged 4-5
      yr (5.10-6.85 kg) during the hypokinetic period of 90 d and during the
      prehypokinetic period of 30 d. They were divided into two equal groups: the first
      group was placed under ordinary vivarium conditions (vivarium control animals)
      and the second group was subjected to 90 d of HK (hypokinetic animals). For the
      simulation of the hypokinetic effect, the primates were immobilized on their
      abdomens in special tables. The legs of the monkeys were immobilized with hip and
      knee joints extended. The primates retained freedom of movement at elbow, wrist,
      and ankle. During the pre-experimental period of 30 d and during the experimental
      period of 90 d, the following variables were determined: body weight, total body
      fluid content, specific total body fluid, mean fluid consumed and eliminated in
      urine, specific plasma resistance, hematocrit level, and plasma concentrations of
      sodium (Na) and potassium (K). In the hypokinetic primates, body weight decreased
      significantly when compared to the controls. Mean fluid intake, total body fluid,
      and specific total body fluid decreased, whereas mean daily fluid loss and
      specific mean daily fluid elimination increased significantly. Specific plasma
      resistance, hematocrit level, and plasma electrolyte concentrations increased
      significantly when compared to the control primates. It was concluded that
      prolonged restriction of motor activity induces significant changes in water
      metabolic parameters of primates leading in decreased total water content of the
      body.

PMID- 9282266
TI  - Formulation for transfollicular drug administration: some recent advances.
AB  - The percutaneous administration of drug products is of current therapeutic
      interest, mainly with regard to reduction of hepatic metabolism and systemic
      toxicity, and delivery to specific sites. Hair follicles and sebaceous glands can
      be privileged pathways for some molecules or formulations, which enter faster
      into these shunts than they do through the stratum corneum. The aim of this paper
      is to outline some examples of recent formulation methodologies that allow
      administration of a drug product through the follicular pathway (1) when the
      common, localized diseases of the pilosebaceous unit could benefit from specific
      delivery; and (2) to shunt the stratum corneum barrier.

PMID- 9282265
TI  - Selenium and antioxidant vitamin and lipidoperoxidation levels in preaging French
      population. EVA Study Group. Edude de vieillissement arteriel.
AB  - Selenium (Se) and antioxidant vitamins might play an important role in the
      etiology of free radical-related diseases and aging. In the Edude de
      vieillissement arteriel (EVA) study, we have determined the plasma thiobarbituric
      acid reacting substances (TBARS) as an indicator of free radical-induced lipid
      peroxidation, plasma selenium and carotenoids, and erythrocyte vitamin E levels
      in 1389 subjects aged 59-71 years. We also looked for an association between
      these parameters and cardiovascular risk factors in early elderly. The results
      show that plasma TBARS were significantly increased in elderly in comparison with
      values reported in younger adults. However, plasma Se and carotenoids as well as
      erythrocyte vitamin E in elderly people are close to those reported in adult
      people. If plasma Se showed no difference between men and women, the three other
      parameters were significantly higher in women than in men. With regard with
      cardiovascular risk factors, plasma TBARS were highly positively correlated with
      total and low-density lipoprotein (LDL) cholesterol in men and women. Plasma
      carotenoids were also positively correlated with plasma total cholesterol and LDL
      cholesterol in both sexes. Finally, plasma TBARS were highly correlated with
      smoking and alcohol consumption. In conclusion, this part of the EVA study shows
      that some cardiovascular risk factors, like smoking and cholesterol level, are
      associated with high free radical-induced TBARS levels in the preaging
      population, although plasma Se and carotenoids as well as erythrocyte vitamin E
      levels in elderly people were close to those reported in adult younger people.

PMID- 9282267
TI  - A human colonic cell line sharing similarities with enterocytes as a model to
      examine oral absorption: advantages and limitations of the Caco-2 model.
AB  - Caco-2 cell monolayers mimic intestinal absorptive epithelium and represent a
      very useful tool for studying transepithelial transport. The literature on Caco-2
      cells is controversial regarding transepithelial resistance and permeabilities of
      different marker compounds across monolayers. This paper discusses probable
      causes for these discrepancies. First, we present the role of culture conditions,
      such as the nature of the support or the passage number, on cell biology and
      transport properties. Further, we compare the presence of transport proteins in
      Caco-2 cells to mammalian intestinal tissue and discuss their implication for
      drug absorption. We also examine the advantages and disadvantages of systems such
      as Transwell and side-by-side diffusion chambers. A summary of comparisons
      between permeabilities across Caco-2 monolayers and mammalian intestinal tissues
      is provided. We conclude that the origin of Caco-2 cells and the culture
      conditions are in part responsible for the discrepancies encountered in the
      literature.

PMID- 9282268
TI  - Targeted delivery of peptides, proteins, and genes by receptor-mediated
      endocytosis.
AB  - Receptor-mediated endocytosis (RME) is one type of delivery system by which
      therapeutic agents can be specifically transported to their target. Although many
      successful studies have been performed at a preclinical level, its clinical
      application is restricted by a number of factors, including the low targeting
      efficiency that stems from the characteristics of RME. One important approach to
      overcome this is to improve the drug delivery system by a series of chemical
      modifications and evaluate the drug targeting efficiency from a kinetic point of
      view.

PMID- 9282269
TI  - Current laparoscopic approaches to pancreatico-biliary disease.
AB  - Biliary-enteric anastomoses to duodenum or jejunum are a laparoscopic reality and
      will find a place in the management of complicated choledocholithiasis or
      malignant strictures of the bile duct. Staging by laparoscopy in pancreatic
      malignancy is an ideal strategy, with some operators able to complete a
      definitive laparoscopic palliative bypass in the same sitting. Intraoperative
      laparoscopic sonography is an advancing technique and has great potential in the
      evaluation of choledocholithiasis, hepatic metastases and staging of pancreatic
      cancer. Innovative options exist to deal with bile duct calculi, including
      antegrade sphincterotomy and intraoperative stent placement.

PMID- 9282270
TI  - Laparoscopic surgery for treatment of splenic disorders: an update.
AB  - Laparoscopic splenectomy is a feasible and safe technique in the hands of skilled
      laparoscopic surgeons. The special characteristics of the spleen, a fragile solid
      organ with a rich vascularization, pose a number of technical questions (patient
      position, organ mobilization and retrieval) which have been successfully resolved
      during the last few years and permit the advantages of laparoscopic surgery to
      become available to patients that need splenectomy.

PMID- 9282271
TI  - Laparoscopic surgery for hiatal hernia and peptic ulceration.
AB  - Antireflux and peptic ulcer surgery are ideally suited for the minimal access
      approach. There is no need for tissue retrieval, nor any compromise of surgical
      principles. Over the last five years there has been a tremendous expansion in
      both the number and types of these laparoscopic procedures and there is little
      doubt that minimal access antireflux surgery is here to stay. Medical therapy is
      expensive and laparoscopic surgery, with a reduction in pain, hospital stay and
      rehabilitation, has become an economic alternative, with the most commonly
      performed procedure being the Nissen fundoplication. Peptic ulcer surgery has
      been slower to develop. The economic argument is not as powerful and it is
      unlikely that we will see much increase in laparoscopic surgical treatment except
      for complications such as perforation, stenosis and bleeding. As yet, series are
      relatively small with early results and we await with interest the long-term
      results.

PMID- 9282272
TI  - Endoscopic surgery of the oesophagus.
AB  - Conventional surgical access to the oesophagus often requires a thoracotomy. The
      application of techniques borrowed from laparoscopic surgery allows transthoracic
      dissection of oesophagus without thoracotomy. These techniques are useful in
      treatment of oesophageal leiomyomas, motility disorders and iatrogenic
      perforations. Oesophageal resection for cancer can be accomplished using minimal
      access, either thoracoscopically or with the aid of an operating mediastinoscope.
      Whether these techniques should replace transthoracic or transhiatal
      oesophagectomy for most patients with cancer remains to be seen.

PMID- 9282273
TI  - Laparoscopic colorectal surgery.
AB  - Laparoscopic surgery has been readily adapted to the management of patients with
      colorectal disease without any large-scale randomized clinical studies to support
      its use, particularly in patients with colorectal cancer. This overview analyses
      the currently available data and highlights the areas where caution is merited
      and optimism encouraged.

PMID- 9282274
TI  - Helicobacter pylori infection and tumour necrosis factor-alpha increase gastrin
      release from human gastric antral fragments.
AB  - OBJECTIVES: To investigate the mechanism of the hypergastrinaemia associated with
      Helicobacter pylori infection by examining the effect of H. pylori infection and
      the cytokine tumour necrosis factor-alpha (TNF-alpha) on gastrin release from
      human antral fragments. DESIGN: In-vitro experimental study. METHODS: Human
      antral biopsy fragments were cultured for 6 h with and without TNF-alpha (20
      ng/ml) and the gastrin released over the following 2-h stimulation period
      measured by radioimmunoassay. The integrity of the paracrine feedback loop
      inhibiting gastrin release was tested by concurrent administration of
      cholecystokinin (CCK). RESULTS: H. pylori-positive fragments were associated with
      significantly greater bombesin-stimulated gastrin release (increased by 40%, P <
      0.05) and less inhibition produced by CCK administration (decreased by 55%, P <
      0.05), than H. pylori-negative fragments. TNF-alpha treatment of H. pylori
      negative fragments significantly enhanced bombesin-stimulated gastrin release (by
      82%, P < 0.01) and diminished inhibitory feedback by CCK (by 53%, P < 0.05).
      CONCLUSION: H. pylori infection is associated with enhanced gastrin release from
      human antrum and TNF-alpha produces a similar effect. Proinflammatory cytokines
      generated in the antrum in response to the infection are likely to play a
      significant role in the hypergastrinaemia of H. pylori infection.

PMID- 9282275
TI  - Reliability of symptom assessment in dyspepsia.
AB  - OBJECTIVE: To examine the variation between doctors in their clinical assessment
      of dyspeptic symptoms. DESIGN: Simulated presentation of three dyspeptic symptom
      complexes to a total of 27 general practitioners, who each interviewed the
      'patient' in accord with their own clinical practice A structured record form was
      used to record details of the history elicited. SETTING: Simulation of a primary
      care consultation. RESULTS: Although overall agreement in symptom assessment was
      reasonable for each of the three symptom complexes, both the accuracy and
      consistency of assessment varied considerably for individual symptoms.
      Inconsistency and inaccuracy in the assessment of epigastric pain were
      unexpectedly large, demonstrating that neither the nature nor severity of pain
      were communicated reliably. CONCLUSION: The findings illustrate the feasibility
      of quantitative appraisal of patient-doctor communication in respect of symptoms
      and show that there is much variation in the reliability with which different
      symptoms are communicated. Difficulty in characterizing abdominal pain reliably
      may contribute to the well recognized inadequacy of a conventional clinical
      history in identifying the cause of a patient's dyspepsia.

PMID- 9282276
TI  - Body composition at the bedside.
AB  - OBJECTIVE: To evaluate the use of an inexpensive hand-held bioelectric impedance
      analysis machine which measures lean body mass, by technical comparisons against
      standard instruments and techniques (an in-house bioelectric impedance machine
      and dual energy X-ray absorptiometry), and by performing body composition
      analyses in groups of potentially malnourished patients. DESIGN: Prospective
      simultaneous comparison of measurements made by the hand-held and in-house
      bioelectric analysis machines and dual energy x-ray absorptiometry. SETTING:
      Medical Physics Department and Gastrointestinal Unit in a university teaching
      hospital. SUBJECTS/METHODS: One hundred and sixty subjects were recruited into
      the study. Data from 58 adolescent and 14 adult volunteers and from 42 adult
      patients were used for technical comparisons (n = 114). Body composition
      information was evaluated (n = 102) for 60 adult volunteers and 42 patients (17
      with eating disorders, 7 with chronic alcoholic pancreatitis and 18 with
      inflammatory bowel disease). OUTCOME MEASURES: Estimation of bias, limits of
      agreement and correlations on data from the three machines. Relationships between
      percentage body mass as lean, absolute weights and body mass index, in the adult
      subjects. RESULTS: Both resistance and calculated impedance measured by the hand
      held machine significantly correlated with the impedance measured by the in-house
      machine (r = 0.996; P < 0.0001). An estimation of the level of agreement in
      percentage lean measurement between dual energy x-ray absorptiometry and hand
      held bioelectrical impedance analysis machine by the Bland and Altman method
      showed a bias of -0.07% and satisfactory limits of agreement from -7.97% to
      7.76%. Body mass index was similar in the groups of healthy men and women, but
      proportion of weight as lean was significantly higher in men than women. In
      underweight patients with eating disorders, the ratio of lean to fat varied
      widely; in inflammatory bowel disease patients, proportions of lean and fat were
      similar to controls; however patients with alcoholic pancreatitis had values for
      body mass index similar to controls, but had significantly lower proportion of
      their body weight as lean (P < 0.05). CONCLUSION: In non-obese and thin adults,
      an accurate two-compartment (lean, fat) measurement of body composition can be
      made in 10 min by using an inexpensive, hand-held, bioelectric impedance analysis
      machine.

PMID- 9282277
TI  - Distribution of cell populations with DNA aneuploidy and p53 protein expression
      in ulcerative colitis.
AB  - OBJECTIVE: Patients with ulcerative colitis are at an increased risk for
      developing colorectal neoplasms. p53 mutations and the occurrence of DNA
      aneuploidies are common events in the development of sporadic colorectal
      neoplasias. This study tried to determine the frequency of these events during
      the development of colitis-associated colorectal neoplasms. DESIGN/METHODS: Four
      colectomy specimens with a total of 124 biopsies were investigated. DNA content
      was measured by flow cytometry and p53 protein expression was detected by
      immunohistochemistry. These results were correlated with histological findings.
      RESULTS: DNA aneuploidies were found in 58 (46.8%), and p53 protein expression in
      30 samples (24.2%). The presence of DNA aneuploidy as well as of p53 protein
      expression correlated with the histological characteristics of neoplastic
      transformation. In areas without dysplasias or with indefinite dysplasias, 31.5%
      of the samples showed DNA aneuploidies and in about 9% of the samples p53 protein
      expression could be detected; 33.7% of samples without or with indefinite
      dysplasias showed p53 protein expression and/or DNA aneuploidies. CONCLUSION:
      These results show that the occurrence of DNA aneuploidies and nuclear p53
      protein expression is a common event in the development of colitis-associated
      colorectal neoplasias. p53 protein expression seems to be an early event in this
      process. DNA aneuploidies occur even earlier and more frequently in the absence
      of p53 protein expression. Therefore, other genetic alterations besides p53 gene
      mutations might be involved in colitis-associated tumour development.

PMID- 9282278
TI  - The changing epidemiological pattern of hepatitis A in Lisbon, Portugal.
AB  - OBJECTIVE: To evaluate the prevalence of anti-hepatitis A virus (HAV) in an urban
      population, in order to assess the changing epidemiological pattern of hepatitis
      A. SUBJECTS: We studied 325 health care workers from Santa Maria Hospital and 201
      students of the Medical School of Lisbon. RESULTS: The prevalence of anti-HAV was
      lower in the younger age groups: 29% in the first 3 years of Faculty compared to
      46% in the last 3 years, P < 0.001. The overall prevalence for students was 35%,
      whereas in health care workers of less than 30 years it was 65%, P < 0.001. These
      findings show a declining prevalence of anti-HAV, particularly in younger age
      groups, when compared with the results obtained in 1983, which showed a
      prevalence of 85%. CONCLUSION: The epidemiological pattern of hepatitis A in
      Lisbon, Portugal, is changing in some urban groups, with prevalences approaching
      those of more developed countries.

PMID- 9282279
TI  - Relationship between splanchnic, peripheral and cardiac haemodynamics in liver
      cirrhosis of different degrees of severity.
AB  - OBJECTIVE: To investigate the relationships between changes in splanchnic and
      systemic haemodynamics in liver cirrhosis. DESIGN AND METHODS: Abdominal and
      peripheral duplex-Doppler sonography and Doppler echocardiography were performed
      in 42 cirrhotic patients with (group A, ascitic) or without ascites (group NA,
      non-ascitic) and in a control group of 36 healthy volunteers. RESULTS: There were
      significant differences (P < 0.05 at ANOVA) between the three groups in portal
      vein flow velocity (controls, groups NA and A, respectively, 29.2, 21.4 and 20.0
      cm/s), portal diameter (9.3, 12.2 and 12.0 mm), superior mesenteric artery (SMA)
      resistance index (RI) (0.889, 0.854 and 0.816), femoral artery RI (0.988, 0.974
      and 0.945), mean arterial pressure (MAP) (101.4, 102.0 and 87.3 mmHg), peripheral
      vascular resistance (1579, 1404 and 1094 dyn/cm5/s) and cardiac index (CI) (2.91,
      3.46 and 3.77 l/min/m2). Multiple regression analysis identified renal
      interlobular- and SMA RI (respectively, r = -0.58 and r = 0.51) in group A as the
      two regional vascular beds correlated to MAP. CONCLUSION: The deterioration of
      the cirrhotic hyperdynamic circulation in the presence of ascites and the
      correlation between MAP and mesenteric and renal resistances are consistent with
      the peripheral arterial vasodilation hypothesis. The positive correlation between
      MAP and SMA RI in ascitic patients shows a link between this region and the
      general circulation. This seems to suggest that splanchnic hyperafflux plays a
      part in the formation of ascites.

PMID- 9282280
TI  - Circulating intercellular adhesion molecule-1 in patients with hepatocellular
      carcinoma.
AB  - BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is thought to play an
      important role in cellular immunological reactions. Expression can be induced by
      inflammatory cytokines in a wide variety of cells, including hepatocytes.
      OBJECTIVE: To compare the behaviour of ICAM-1 in liver diseases. PATIENTS AND
      METHODS: We assayed serum ICAM-1 (sICAM-1) in patients with hepatocellular
      carcinoma-associated liver cirrhosis, and compared them with a group of cirrhotic
      patients and controls. sICAM-1 values were also correlated with some biochemical
      parameters of liver function. Moreover, immunohistochemical localization of ICAM
      1 was performed on liver tissue sections of patients with hepatocellular
      carcinoma, liver cirrhosis and a sample of normal liver. RESULTS: sICAM-1 levels
      were significantly higher in the hepatocellular carcinoma patients than in
      controls (P < 0.0001) and the cirrhosis group (P < 0.001). sICAM-1 values
      directly correlated with alanine aminotransferase, total bilirubin, alkaline
      phosphatase and gamma-glutamyltranspeptidase serum values (P < 0.05), with an
      inverse correlation with albuminaemia values (P < 0.05). There was no correlation
      with alpha-fetoprotein values, but sICAM-1 values were higher in hepatocellular
      carcinoma patients with large tumours (> 3 cm) than in those with small tumours
      (< 3 cm) (P < 0.04). Immunohistochemical localization of ICAM-1 was negative in
      normal liver tissue; positive staining for endothelial cells was found in chronic
      liver disease, while in hepatocellular carcinoma tissues, positive membrane
      staining was observed in hepatocytes and, to a lesser extent, at the cytoplasmic
      level. CONCLUSION: These results suggest that high serum levels of sICAM-1 are
      associated with severe liver disease, such as liver cirrhosis and hepatocellular
      carcinoma, and that they tend to increase with deteriorating hepatic function and
      tumour size.

PMID- 9282281
TI  - Omeprazole induces a long-term clinical remission of protein-losing gastropathy
      of Menetrier's disease.
AB  - We report a patient with Menetrier's disease presenting with extensive
      subcutaneous oedema, ascites and pleural effusion due to hypoalbuminaemia.
      Gastric secretory studies showed no free basal and stimulated acid secretion. The
      gastric juice contained significant amounts of albumin (0.2 g/dl) and
      immunoglobulin G (IgG) (1.11 mg/dl), corresponding to an estimated daily loss of
      9.7 g and 45 mg, respectively. Protein-losing gastropathy was initially
      unsuccessfully treated with famotidine (80 mg/day) for 17 months, but a long-term
      (25 months) clinical remission was subsequently achieved with omeprazole (20
      mg/day). We suggest that excellent clinical remission of Menetrier's disease and
      the associated protein-losing gastropathy may be obtained with long-term
      omeprazole maintenance treatment, possibly due to Helicobacter pylori
      suppression.

PMID- 9282282
TI  - Idiopathic hypereosinophilic syndrome presenting as cholestatic liver disease.
AB  - We report the case of a 34-year-old white man with recurrent episodes of
      abdominal pain, cholestasis and eosinophilia. The diagnosis of idiopathic
      hypereosinophilic syndrome (IHS) was made after exclusion of all known causes of
      eosinophilia. Liver biopsy revealed an eosinophilic infiltrate with biliary
      damage. The patient recovered after prednisolone treatment. We review the
      literature on the association between IHS and liver disease.

PMID- 9282283
TI  - Collagenous colitis and cimetidine.
AB  - We report a case of a 62-year-old man who developed watery diarrhoea after
      starting treatment with cimetidine for dyspepsia. Macroscopically, sigmoidoscopy
      and colonoscopy were normal. Histology revealed features consistent with a
      diagnosis of collagenous colitis. The diarrhoea is responding to treatment with
      prednisolone and withdrawal of cimetidine. We conclude that the collagenous
      colitis may have been drug induced.

PMID- 9282284
TI  - Coronary restenosis after optimal (stent-like) initial angiographic results
      obtained by traditional balloon angioplasty.
AB  - BACKGROUND AND OBJECTIVE: Elective native coronary artery stenting has shown its
      efficacy in lowering restenosis rates (RR) usually occurring after balloon
      angioplasty (PTCA). However ability of conventional PTCA to consistently provide
      low RR, through the achievement of large acute stent-like angiographic results,
      has not been investigated. This study was conducted to: (1) assess ability of
      optimal initial dilatation (OID), defined by residual lumen narrowing < or = 20%,
      significantly reduce current high RR following traditional PTCA; (2) evaluate the
      efficacy of OID obtainable by conventional PTCA in influencing adverse effects of
      single variables predisposing to restenosis. METHODS: Of consecutive 601 patients
      who underwent PTCA, 569 (94.6%), 483 men and 86 women, aged 38-76 years, had a
      successful procedure on 645/678 lesions (95.1%). After a plaque fracture was
      obtained by the first inflation, step-increases in pressure of 1 atm and 60
      second-inflation-times were applied, until a large lumen (the nearest to normal)
      and smooth contours were seen, or any wall damage detected by using step-by-step
      angiographic tests. Acute optimal results (group A) were 450 (69.7%) and sub
      optimal results (group B) were 203 (30.3%). After a mean time of 9 +/- 1.8
      months, 543 patients (95.4%) had angiographic restudy on 611 (94.7%) successfully
      treated lesions. RESULTS: Restenosis (> 50% stenosis at restudy) occurred in
      27.1% of patients and in 24.5% of lesions. RR was 18.8% in group A and 37.8% in
      group B (p < 0.0001). Significant lower RR were observed in group A in comparison
      with group B, for single variables examined, except for length > 10 mm. By
      multivariate analysis of all treated lesions, sub-optimal initial dilatation,
      unstable angina, lesion length > 10 mm and eccentricity emerged as major
      determinants of restenosis. Following OID only length > 10 mm was highly
      predictive of this event and, in the absence of this adverse variable, RR was
      only 13.6%. CONCLUSION: Counterbalancing adverse effects of many variables
      predisposing to restenosis, OID obtained by traditional PTCA seem to
      significantly reduce the risk of recurrence, particularly in lesions no longer
      than 10 mm.

PMID- 9282285
TI  - Intracoronary stenting for thrombus-containing lesions in the setting of acute
      ischemic syndromes.
AB  - AIM: The presence of intracoronary thrombus was considered a contraindication for
      stent deployment. Recently, many investigators have demonstrated that the use of
      stents for thrombus-laden lesions under both elective and bail-out conditions is
      effective and safe, even in the setting of acute myocardial infarction (AMI).
      METHODS AND RESULTS: In this study Palmaz-Schatz stents were implanted to treat
      suboptimal results and complications of percutaneous transluminal coronary
      angioplasty (PTCA) in 41 thrombus-containing lesions. Clinical presentation was
      unstable angina in 24 and AMI in 17 patients. Stents were deployed because of
      suboptimal result (n = 27), coronary dissection with threatening occlusion (n =
      13) or abrupt closure (n = 1). An angiographic successful deployment was obtained
      in all but one lesions (98%). Four patients (9.8%) suffered from in-hospital
      complications: three developed a non fatal non-Q wave AMI and one died. There was
      no need for emergency coronary artery bypass graft surgery, repeat PTCA or blood
      transfusion for vascular complications. At six-months follow-up one patient
      (2.6%) developed a non-Q wave AMI and two (5.1%) underwent a repeat coronary
      angioplasty. CONCLUSIONS: Our experience confirms that adequately dilated Palmaz
      Schatz stent might be safe and effective for thrombus-containing lesions in the
      setting of acute ischemic syndromes.

PMID- 9282286
TI  - Incidence of major coronary heart disease events: the experience of the Project
      "Community Control of Chronic Diseases".
AB  - Data on incidence of first major coronary heart disease (CHD) event have been
      collected in a population sample studied in the control area, the municipality of
      Priverno in Central Italy, 100 km South-East of Rome as part of a Community
      Control Project of Chronic Diseases run in nearby communities. Men and women aged
      40-69 years, examined in population screenings, were followed-up for variable
      periods of time ranging from 1 month to 11 years, after exclusion of those
      already carrier of a previous major CHD event. A total of 1427 men and 1675 women
      corresponding to a maximum of 9590 and 11499 person/years respectively were
      followed-up. Diagnostic criteria were based on a number of different items
      including history and ECG data, from screening examinations; discharge records
      from local hospitals; causes of death from death certificates; and information
      from mail questionnaires. Four hundred and forty-six men and 501 women were
      considered partially non respondent since they were examined only once, they did
      not answer the postal questionnaire, although they were surely alive at the end
      of the observation period. Incidence estimates were based on different
      denominators, including or excluding these non respondents. The age adjusted
      lower incidence estimate was of 40.7 per 10000 person/years among men and 19.7
      among women; the higher estimate was of 51.3 and 24.4 per 10000 person/years
      respectively. Rates were higher among men than among women and were increasing
      with aging. These incidence rates were slightly lower than those reported from
      other population studies conducted in Italy in the 1970's and the 1980's, but
      were in line with the hypothesis of a declining incidence paralleling the decline
      in CHD mortality. These data, including also estimates in women, represent a
      reference point for the early 1990's of the frequency and distribution of major
      CHD events.

PMID- 9282288
TI  - A closed hole.

PMID- 9282287
TI  - Transcatheter repair of a large coronary pseudoaneurysm using ultrasound guidance
      and vein-covered stents.
AB  - This case-report describes a large pseudoaneurysm of the proximal left anterior
      descending coronary artery, fissured in the pericardium, developed 4 days after
      rotational and directional atherectomy followed by stent implantation. A
      successful percutaneous repair was obtained with 2 vein-covered stents implanted
      and expanded under ultrasound guidance.

PMID- 9282289
TI  - Doppler tissue imaging in the new era of digital echocardiography.
AB  - Doppler tissue imaging is one of the most recent technical achievements of
      clinical echocardiography. Different Doppler modes are encompassed by Doppler
      tissue imaging: tissues velocity, pulsed wave-doppler, acceleration, phase,
      synchronicity and energy modes. With the exception of the energy mode, all modes
      are based on the Doppler shift, according to the strength of the Doppler signals
      from the tissues. The most widely used mode is tissue velocity, in which the
      velocity of moving tissue is calculated in relation to the transducer from the
      Doppler shift and is displayed as colour-encoded velocity maps in M-mode and two
      dimensional imaging formats. Both curved M-mode, applied on two-dimensional
      images, and three-dimensional reconstruction appear among the most promising
      applications of velocity mode for the quantitative assessment of regional left
      ventricular function. A second Doppler mode, pulsed wave-doppler tissue imaging,
      displays the velocity profile of a region of interest versus time. The velocity
      data are displayed with a high temporal resolution, but with the disadvantage of
      a low spatial resolution. A third Doppler mode, tissue acceleration, displays the
      differences in velocity between subsequent frames in colour-encoded maps. A
      clinical application has been found in the electrophysiologic field. Other
      Doppler modes, phase and synchronicity, still require clinical assessment.
      Lastly, the tissue energy or power mode displays the strength of the Doppler
      signal from the tissues as gradations of the colour intensity in colour-encoded
      maps. One of its fields of application appears to be the study of myocardial
      perfusion with contrast agents. The development of new dedicated algorithms for
      colour quantification, along with the beginning of the new era of digital
      echocardiography, should help bring Doppler tissue imaging into the clinical
      arena.

PMID- 9282290
TI  - [Clinical results of extracorporeal shock wave lithotripsy for upper urinary
      tract stone using Siemens Lithostar2].
AB  - Between May 1994 and March 1996, a total of 427 cases of upper urinary tract
      stones were treated by extracorporeal shock wave lithotripsy (ESWL) using a
      Siemens Lithostar2. Of 427 patients, 167 had renal stones and 260 had ureteral
      calculi. A double J stent was inserted preoperatively for patients with stones >
      or = 20 mm in diameter. The success rate after 3 months, defined as complete
      disappearance of stone or partial disintegration with residual stones < or = 4 mm
      in diameter, was 82.4% and 88.1% for the renal and ureteral calculi,
      respectively. Additional treatments were required in 9 cases (transurethral
      ureterolithotripsy in 5, percutaneous nephrostomy in 2, nephrolithotripsy and
      ureterolithotomy in 1 each). There were no serious side effects requiring
      surgical treatment or blood transfusion, although perirenal hematoma developed in
      5 patients, who were treated conservatively. It is concluded that ESWL using
      Simens Lithostar 2 is safe and useful for treating upper urinary tract stones.

PMID- 9282291
TI  - [Clinical investigation of prostatic cancer patients who underwent radical
      prostatectomy: analysis of patients in the Tokai Urological Cancer Registry].
AB  - Between 1989 and 1991, 815 cases of prostatic carcinoma were registered in the
      Tokai Urological Cancer Registry. We investigated the clinical features and
      prognosis of 69 patients who underwent radical prostatectomy. The median age and
      clinical stage, were 65.9 +/- 4.7 years and A in 7 patients, 66.3 +/- 5.8 years
      and B in 31, 68.2 +/- 2.7 years and C in 26, 63.4 +/- 13.5 years and N(+) in 5.
      Neoadjuvant therapy consisting of endocrine therapy and chemoendocrine therapy
      was administered to 28 and 14 patients, respectively. In comparison to the
      clinical stage, pathologically, 4 cases (9.5%) showed downstaging or overstaging,
      15 (35.7%) understaging and 23 (54.8%) accurate staging in the neoadjuvant
      therapy group, and, respectively, 2 (7.4%), 12 (44.4%) and 13 (48.2%) in the non
      neoadjuvant therapy group. There was a significant difference in the pretreatment
      prostatic antigen (PA) value between pT0 and pT3 (p < 0.05), between pT0 and
      pN(+) (p < 0.01) and between pT2 and pN(+) (p < 0.05). In addition, the
      pretreatment PA value in the recurrence group was higher than that in the non
      recurrence group in both neoadjuvant and non-neoadjuvant groups, with a
      significant difference (p < 0.01) in the neoadjuvant group. Cancer recurrence was
      noticed in 2 patients given non-neoadjuvant therapy and 3 given neoadjuvant
      therapy. There was no significant difference in the non-recurrence rate with the
      pathological stage either with or without neoadjuvant therapy. However, the non
      recurrence rate in the neoadjuvant therapy group was higher than that in the non
      neoadjuvant therapy group.

PMID- 9282292
TI  - [Transurethral electrovaporization of the prostate (TUV-P): comparative study
      with transurethral resection (TUR-P)].
AB  - A total of 27 patients with benign prostatic hyperplasia were treated by
      transurethral electrovaporization of the prostate (TUV-P). A roller bar electrode
      was used for 13 patients and a roller loop electrode for 14. Therapeutic efficacy
      and complications of TUV-P were compared with those of transurethral resection of
      the prostate (TUR-P) performed before TUV-P was started (24 patients). The
      improvements in subjective symptom scores and objective voiding parameters after
      3 months were not significantly different between the TUV-P and TUR-P groups.
      Furthermore, the improvements were similar between TUV-P using the roller bar and
      the roller loop. No patients treated by TUV-P had TUR syndrome or received blood
      transfusion, while blood transfusion was performed in 4 patients treated by TUR
      P. Postoperative duration of urethral catheterization and hospital stay was
      significantly shorter in the TUV-P group than in the TUR-P group. The operative
      time for TUV-P (roller bar) was 1.6 min per g. preoperative prostate volume,
      while that for TUV-P (roller loop) and TUR-P was 2.1 and 1.9 min/g, respectively.
      From our experience, TUV-P was as effective as TUR-P for relieving bladder outlet
      obstruction with fewer complications. Furthermore, the operative time could be
      shortened with a roller loop.

PMID- 9282293
TI  - [Clinical results of transurethral electrovaporization of prostate (TVP)].
AB  - Transurethral electrovaporization of prostate (TVP) is a new minimally invasive
      procedure to treat enlargement of prostate. From April 1996 to the end of
      October, TVP was carried out in 37 cases (mean age, 71.0) with symptoms of
      urethral obstruction. Standard transurethral resection equipment was utilized.
      This included a Stortz 26F resectoscope with a Conmed SABRE 2400 electrical
      current generator. A Stortz 3 mm Spike Electrode was used as the vaporization
      electrode. The average setting was 250 W for cutting and 80 to 100 W for
      coagulation. Efficacy parameters evaluated included International Prostate
      Symptom Score, peak uroflow and postvoid residual volume. By the end of January
      1997, 28 cases could be followed up for more than three months after surgery and
      evaluated. Postvoid residual volume decreased from 68 to 10 and 17 ml at 1 and 3
      months. Peak uroflow increased from 8.5 to 15.1 and 17.9 ml/sec at 1 and 3
      months. All 28 cases were categorized as effectively treated cases at 1 and 3
      months postoperatively. TVP was found to have several advantages, particularly
      minimal bleeding and the low incidence of postoperative morbidity. The technique
      is simple and symptoms improve at an early stage following surgery. We intend to
      continue longer follow up with larger numbers of patients.

PMID- 9282294
TI  - [A case of retroperitoneal fibrosarcoma in the perirenal space].
AB  - A case of retroperitoneal fibrosarcoma is reported. A 52-year-old man with the
      complaint of left abdominal mass was referred to our hospital. Computed
      tomography showed a left retroperitoneal tumor surrounding the left kidney in the
      perirenal space. Angiography showed some feeding vessels from the branch of the
      posterior segmental artery of the left kidney. The tumor was completely resected
      with the left kidney, but para-aortic lymph node metestases were found.
      Histopathological diagnosis was a retroperitoneal fibrosarcoma with lymph node
      metastases. The patient died of the disease 3 months after the operation.

PMID- 9282295
TI  - [Renal cell carcinoma diagnosed by ring-like growth of preexistent calcification:
      a case report].
AB  - A 53-year-old woman was referred for further examination of a left renal cyst
      detected ultrasonographically during a health checkup. Computerized tomography
      (CT) scan and magnetic resonance imaging revealed an irregular cystic mass at the
      center of the left kidney as well as a calcified lesion at the left upper pole.
      Angiography and cyst puncture confirmed the cystic mass to be unilocular and
      benign. However, followup CT scan after 22 months demonstrated enlargement of the
      calcification into a ring-like configuration 3 cm in diameter. Since the lesion
      showed neovascularity on angiography, radical nephrectomy was performed.
      Histopathological diagnosis was renal cell carcinoma, alveolar type, common type
      at the center, but solid type, spindle cell type at the periphery.

PMID- 9282296
TI  - [A case of transitional cell carcinoma of renal pelvis with extremely high serum
      levels of CA19-9 and CEA].
AB  - We report a case of transitional cell carcinoma of the renal pelvis with
      extremely high serum levels of carbohydrate antigen 19-9 (CA19-9) and
      carcinoembryonic antigen (CEA). A 69-year-old woman was admitted with gross
      hematuria. Imaging diagnosis revealed a tumor in the left renal pelvis and
      multiple liver and bone metastases. Serum levels of CA19-9 and CEA were 2,557
      U/ml (normal < 36) and 523 ng/ml (normal < 3.8), respectively. She died of cancer
      progression 3 weeks after admission. An autopsy diagnosis was transitional cell
      carcinoma of the left renal pelvis. No abnormal findings were recognized in the
      gastrointestinal organs. Cancer cells showed a positive immunohistochemical
      staining for both CA19-9 and CEA.

PMID- 9282297
TI  - [A case of bilateral upper urinary tract tumors after radical cystectomy].
AB  - We report a case of bilateral upper urinary tract tumors after total cystectomy.
      A 67-year-old male with multiple bladder tumors underwent total cystectomy and
      ileal conduit urinary diversion. Pathological diagnosis was transitional cell
      carcinoma, grade 3 (G3), pT1b. Followup urinary cytology continued to be
      negative. Percutaneous antegrade pyelography revealed multiple bilateral upper
      urinary tract tumors 21 months post-operatively. Bilateral nephroureterectomy and
      resection of ileal conduit were performed. Pathological examination revealed
      transitional cell carcinoma, G3 in bilateral pelvis and ureter. Routine careful
      examination is necessary after total cystectomy.

PMID- 9282298
TI  - [A case of spontaneous repair of the ureteral rupture caused by ureteral
      carcinoma].
AB  - We report a 47-year-old male patient with a spontaneous ureteral rupture caused
      by ureteral carcinoma. Drip infusion pyelography (DIP) and computerized
      tomography (CT) demonstrated the extravasation of contrast medium around the
      dilated upper ureter. Nephrostography showed the extinction of extravasation 4
      days after the DIP. A total nephroureterectomy with the excision of a cuff of
      bladder was performed for the transitional cell carcinoma of the right lower
      ureter. Meticulous pathological examination of the specimen revealed
      discontinuity of the muscle layer, edema and fibrin deposition in the submucosal
      layers in the upper ureter indicating the site of the rupture. These findings
      suggest that the spontaneous rupture of the ureter caused by the ureteral
      carcinoma could be spontaneously repaired in a short period.

PMID- 9282299
TI  - [Primary carcinoma of ureter with glandular metaplasia of transitional cell
      carcinoma: a case report].
AB  - A case of primary mixed carcinoma of the right ureter in a 62-year-old woman is
      reported. Histopathology following a nephroureterectomy revealed well
      differentiated adenocarcinoma with a component of transitional cell carcinoma at
      the base of the tumor, suggesting glandular metaplasia of transitional cell
      carcinoma.

PMID- 9282300
TI  - [Spontaneous rupture of the urinary bladder in a woman with radiation cystitis: a
      case report].
AB  - A 79-year-old woman was admitted to our hospital with gross hematuria and
      abdominal pain. She had had a uterine cancer 11 years previously and received 56
      Gy 60Co external irradiation combined with 129 Gy 137Cs internal irradiation. She
      had a sign of pan-peritonitis. An emergency operation revealed an intraperitoneal
      rupture of the dome of the urinary bladder 8 cm in length. Because a primary
      suturing of the bladder wall was unsuccessful, bilateral cutaneous ureterostomy
      was performed. Histologically, the ruptured bladder wall showed a mucosal erosion
      and fibrosis of the muscle layer.

PMID- 9282301
TI  - [A case of infant testicular tumor diagnosed ultrasonographically in the prenatal
      period].
AB  - We report a case of testicular tumor detected by ultrasonography during the
      prenatal period. Ultrasonography performed at 32 weeks of gestation showed that
      one testis was larger than the other. The right testis was markedly enlarged at
      38 weeks of gestation. The heterogeneous echo pattern of the right testis
      suggested a testicular tumor. Right high orchiectomy was performed 3 months after
      birth. Pathological findings of the tumor were teratoma with mature and immature
      components according to the histological classification of testicular tumor. In
      Japan, this is the second case diagnosed in the prenatal period using
      ultrasonography.

PMID- 9282302
TI  - [Simultaneous bilateral testicular tumors with different cell types: a case
      report].
AB  - A 26-year-old man presented with a painless mass in the right scrotum. Physical
      examination revealed another smaller mass in the left testis. The patient
      underwent right radical orchiectomy and enucleation of the tumor in the left
      testis, followed by radiotherapy for right iliac and para-aortic lymph nodes up
      to a total dose of 30 Gy. Histology proved typical seminoma of the right testis
      and mature teratoma in the left testis. Imaging study including abdominal CT and
      chest X-ray and prompt lowering of beta-HCG level within the normal limit after
      surgery confirmed the diagnosis of stage I disease. Human leukocyte antigen (HLA)
      A24 was identified in this case, suggesting its potential association with
      bilateral testicular tumor. He is now leading an uneventful life without
      recurrence of the disease at 30 months after surgery.

PMID- 9282303
TI  - [Clinical phase III study of cimetropium bromide (DA3177) on the pain with upper
      urinary calculus: a double-blind study in comparison with scopolamine
      butylbromide. DA3177 Study Group].
AB  - A double-blind study was conducted to evaluate the efficacy, safety and
      usefulness of cimetropium bromide (DA3177) in the patients with pain caused by
      upper urinary calculus at a daily dose of 75 mg t.i.d. (Group D, 97 patients) in
      comparison with scopolamine butylbromide at a daily dose of 60 mg t.i.d. (Group
      B, 101 patients). According to patient's impression, the rate of "moderately
      improved" or better was significantly higher in Group D (68.7%) than in Group B
      (53.5%; Wilcoxon 2 sample test: p = 0.0044). For pain, the rate of "moderately
      improved" or better was 69.1% in Group D and 60.4% in Group B. In global
      improvement, the rate of "moderately improved" or better was significantly higher
      in Group D (70.1%) than in Group B (61.4%; Wilcoxon 2 sample test: p = 0.0469).
      The rate of "no problem in safety" showed no significant difference between Group
      D (91.5%) and Group B (93.3%). Adverse reactions occurred in 8.5% in Group D and
      6.7% in Group B. The major adverse reactions were "dry mouth", "abdominal
      distension", "constipation" and "nausea". The rate of "useful" or better was
      68.7% in Group D, and 60.4% in Group B. In conclusion, DA3177 was confirmed to be
      a useful drug for patient with pain caused by upper urinary calculus.

PMID- 9282304
TI  - c-myc, c-H-ras, and IP3 elevation in 18:2 n-6 dependent proliferation of lung
      cells.

PMID- 9282305
TI  - Virus susceptibilities of new cell lines from embryos of the whitemarked tussock
      moth.

PMID- 9282306
TI  - A stable transfected line of human glomerular epithelial cells.

PMID- 9282307
TI  - Responses of HUVEC and EAhy926 to heparin and fibroblast growth factors.

PMID- 9282308
TI  - Environmental chemical carcinogens induce transformation of breast epithelial
      cells from women with familial history of breast cancer.

PMID- 9282311
TI  - An insect cell line discrimination method by RAPD-PCR.
AB  - RAPD-PCR with a tenmar single primer for discrimination of insect cell lines was
      devised. The base sequence of the primers used were TTCGAGCCAG, CGGCATCTAC,
      GAACGGACTC, and TGAGTGGGTG (GC contents were 60%). Genome DNA was extracted by
      modified Landry et al. (1993) method. The reaction mixture consisted of 10
      microliters buffer, 8 microliters dNTP mixture (2.5 mM each), 4 microliters
      primer (50 microM), Taq DNA polymerase (2.5 units), 1 microliter template DNA;
      and the reaction was run at 94 degrees C for 2 min (denaturation), followed by 31
      cycles of 94 degrees C for 1 min, 42 degrees C for 1 min (annealing), and 72
      degrees C for 2 min (extension) and terminated with 72 degrees C for 7 min. By
      developing the reaction products with agarose gel electrophoresis, it became
      evident that DNA fragments were amplified with all the primers used. Among four
      primers, the second primer was selected as a suitable primer for distinguishing
      cell lines. With this method, cell lines derived from different species were
      clearly distinguished.

PMID- 9282309
TI  - Recoverin expression in the R28 retinal precursor cell line.

PMID- 9282310
TI  - Enhanced growth of canine bone marrow stromal cell cultures in the presence of
      acidic fibroblast growth factor and heparin.
AB  - The ex vivo establishment, expansion, transduction, and reintroduction of
      autologous bone marrow stromal cells offers a potential efficacious system for
      somatic cell gene therapy. It is likely that any ex vivo system will require the
      use of large numbers of cells which express high levels of transgene products. We
      present a method for routine expansion of canine bone marrow stromal cells,
      established from initial 10-20 ml marrow aspirates, to greater than 10(9) cells.
      This high level expansion of cell cultures uses the stimulatory effect of acidic
      fibroblast growth factor (aFGF) and heparin. In the absence of these factors,
      stromal cell cultures grow actively for only 1 to 2 passages, become flattened in
      morphology, and expand to only 10(8) cells. In the presence of heparin (5 U/ml),
      aFGF exerts its effect over a wide range of concentrations (0.1-10 ng/ml) in a
      dose-dependent manner. The stimulatory effect is dependent on the presence of
      both aFGF and heparin. Immunocytochemical and cytochemical analyses
      phenotypically characterize these stromal cells as bone marrow stromal
      myofibroblasts. Stromal cells grown in the presence of aFGF and heparin grow
      actively and maintain a fibroblast-like morphology for a number of passages,
      transduce efficiently with a human growth hormone (hGH) expression vector, and
      express and secrete high levels of hGH. Human marrow stromal cells were also
      established and expanded by the same culture method. This culture method should
      be of great value in somatic cell gene therapy for the delivery of secreted gene
      products to the plasma of large mammals.

PMID- 9282312
TI  - Cadmium (Cd2+) disrupts E-cadherin-dependent cell-cell junctions in MDCK cells.
AB  - Previous studies from our laboratory have shown that Cd2+ can selectively disrupt
      E-cadherin-dependent cell-cell junctions in the porcine renal epithelial cell
      line, LLC-PK1. The objective of the present studies was to determine whether or
      not Cd2+ could produce similar effects in Madin-Darby canine kidney (MDCK) cells,
      an immortal epithelial cell line derived from dog kidney. This is an important
      issue because MDCK cells have been used extensively as a model system to study
      the basic mechanisms of E-cadherin-dependent cell-cell adhesion. MDCK cells on
      permeable membrane supports were exposed to Cd2+ by adding CdCl2 to either the
      apical or the basolateral compartment. The integrity of cell-cell junctions was
      assessed by morphologic observation of the cells and by monitoring the
      transepithelial electrical resistance. The results showed that exposure to 10-40
      microM Cd2+ for 15 min-4 h caused the cells to separate from each other without
      detaching from the growing surface. The separation of the cells was accompanied
      by a marked drop in the transepithelial electrical resistance, a loss of E
      cadherin from the cell-cell contacts, and a reorganization of the actin
      cytoskeleton. These effects were much more pronounced when Cd2+ was added
      basolaterally than when it was added apically. Moreover, the effects of Cd2+ were
      qualitatively similar to those observed when the cells were incubated in Ca(2+)
      free medium. These results show that Cd2+ can disrupt E-cadherin-dependent cell
      cell junctions in MDCK cells, and they indicate that this cell line would be an
      appropriate model for further mechanistic studies in this area.

PMID- 9282313
TI  - Effects of iron chelates on the transferrin-free culture of rat dermal
      fibroblasts through active oxygen generation.
AB  - Effects of nonchelating and chelating agents at 10 mM on the serum-free culture
      of rat dermal fibroblasts were investigated. A strong iron-chelating agent,
      iminodiacetic acid (IDA), and a weak one, dihydroxyethylglycine (DHEG), decreased
      iron permeation into preconfluent fibroblasts. A weak iron-chelating agent,
      glycylglycine (GG), a nonchelating agent, N-2-hydroxyethylpiperazine-N'-2
      ethanesulfonic acid (HEPES), and human apotransferrin (10 micrograms/ml)
      increased the permeation with time. Iron may be essential for survival of
      fibroblasts because subconfluent fibroblasts exposed to 100 microM FeSO4 in
      combination with transferrin, HEPES, or GG significantly decreased to release
      lactate dehydrogenase into the medium. Superoxide dismutase and dimethyl
      sulfoxide blocked the enzyme release, suggesting that superoxide and hydroxyl
      radical induce cellular damage but hydrogen peroxide (H2O2) generated by
      superoxide dismutation does not. GG significantly reduced H2O2 cytotoxicity. DHEG
      acted as a potent promoter of the iron-stimulated cellular damage if ascorbate or
      H2O2 was added to the medium. FeSO4 and FeCl3 (50 to 100 microM) individually
      combined with IDA maximally promoted fibroblast proliferation. Ascorbate
      increased formation of thiobarbituric acid-reactive substances from deoxyribose
      in the medium supplemented with FeSO4 and either IDA or DHEG. Conversely,
      ascorbate decreased the formation in the medium with FeSO4 and with or without
      other agents. Fibroblast proliferation may thus be stimulated through the active
      oxygen generation mediated by a redox-cycling between Fe3+ and Fe2+, which are
      dissolved in the medium at a high concentration, rather than through delivery of
      iron into the cells.

PMID- 9282314
TI  - Isolating and maintaining highly polarized primary epithelial cells from normal
      human duodenum for growth as spheroid-like vesicles.
AB  - A method is described for the three-dimensional (3-D) in vitro culture of
      nontransformed gastrointestinal epithelial cells from the human duodenal mucosa.
      Biopsies obtained from human duodenum were finely minced. The tissue fragments
      were suspended in culture medium supplemented with 5% fetal calf serum and the
      appropriate antibiotics. The suspended mucosal fragments generated spheroid-like
      multicellular vesicles consisting of highly prismatic absorptive and goblet cells
      retaining most of the histological features of the tissue in vivo. We performed
      immunocytochemical studies to determine the origin of the vesicles using
      monoclonal antibodies against EP4. The histochemistry of the vesicles showed
      alkaline phosphatase activity. Ultrastructural studies revealed that these cells
      exhibit characteristics of normal duodenal cells in vivo: apical microvilli,
      glycocalyx, tight junctions and desmosomes, lateral membrane interdigitations,
      mucous droplets, and a well-developed Golgi apparatus. An overgrowth of the
      vesicles by fibroblasts was not seen during cultivation. In contrast with the two
      dimensional cell cultures grown on artificial supports, the vesicle cells show
      organization similar to that of natural epithelia. The polarization and
      cytoarchitecture of normal gastrointestinal epithelial cells cultured as 3-D
      vesicles are comparable to those known for the native tissue. This study was
      undertaken to provide a morphological baseline for subsequent infection
      experiments.

PMID- 9282315
TI  - Functional and morphological differentiation of nonpigmented ciliary body
      epithelial cells grown on collagen rafts.
AB  - We have examined the effect of alteration in cell shape on promoting
      differentiated morphology and physiology in cultured nonpigmented epithelial
      cells from the ciliary body. We have grown pure populations of nonpigmented cells
      on collagen gels released from the culture dish to create collagen rafts. Shortly
      after the gels were detached, the cells shrank in diameter and increased in
      height while they contracted the gel. Concurrently, the actin cytoskeleton
      reorganized to the cell cortex as found in vivo. After this differentiated
      morphology developed, large changes in intracellular Ca2+ could be elicited by
      simultaneous activation of acetylcholine and epinephrine or acetylcholine and
      somatostatin receptors as seen in intact tissue. Explant cultures of isolated
      nonpigmented cell layers maintained their actin distribution and also showed
      synergistic Ca2+ increases. Spread cells, grown on rigid substrates, had a
      disorganized cytoskeleton and rarely showed synergism. These data suggest that
      the mechanism underlying synergistic Ca2+ responses in the ciliary body is
      functional in nonpigmented cells grown on collagen rafts. In addition, this
      pathway appears to be sensitive to the disposition of the cell's
      cytoarchitecture.

PMID- 9282317
TI  - Modulation of mitogen-independent hepatocyte proliferation during the perinatal
      period in the rat.
AB  - Late gestation fetal rat hepatocytes can proliferate under defined in vitro
      conditions in the absence of added mitogens. However, this capacity declines with
      advancing gestational age of the fetus from which the hepatocytes are derived.
      The present studies were undertaken to investigate this change in fetal
      hepatocyte growth regulation. Examination of E19 fetal hepatocyte primary
      cultures using immunocytochemistry for 5-bromo-2'-deoxyuridine (BrdU)
      incorporation showed that approximately 80% of these cells traverse S-phase of
      the cell cycle over the first 48 h in culture. Similarly, 65% of E19 hepatocytes
      maintained in culture under defined mitogen-free conditions for 24 h showed
      nuclear expression of proliferating cell nuclear antigen (PCNA). These in vitro
      findings correlated with a high level of immunoreactive PCNA in immunofluorescent
      analyses of E19 liver. In contrast, E21 (term) liver showed little immunoreactive
      PCNA. The in vivo finding was recapitulated by in vitro studies showing that E21
      hepatocytes had low levels of BrdU incorporation during the first day in culture
      and were PCNA negative shortly after isolation. However, within 12 h of plating,
      E21 hepatocytes showed cytoplasmic staining for PCNA. Although maintained under
      mitogen-free conditions, PCNA expression progressed synchronously to a nucleolar
      staining pattern at 24 to 48 h in culture followed by intense, diffuse nuclear
      staining at 60 h which disappeared by 72 h. This apparently synchronous cell
      cycle progression was confirmed by studies showing peak BrdU incorporation on the
      third day in culture. Whereas DNA synthesis by both E19 and E21 hepatocytes was
      potentiated by transforming growth factor alpha (TGF alpha), considerable mitogen
      independent DNA synthesis was seen in hepatocytes from both gestational ages.
      These results may indicate that fetal hepatocytes come under the influence of an
      exogenous, in vivo growth inhibitory factor as term approaches and that this
      effect is relieved when term fetal hepatocytes are cultured.

PMID- 9282316
TI  - Secretion of ribonucleases by normal and immortalized cells grown in serum-free
      culture conditions.
AB  - The requirement of serum in cell culture is a major limitation for studies on
      secreted ribonucleases (RNases) because serum contains a high amount of
      ribonucleolytic activity. Defined culture condition is thus of interest to
      improve our knowledge of the RNase biology. We report here that cells from three
      different types and origins, Chinese hamster lung fibroblasts, bovine smooth
      muscle cells, and human endothelium-derived EA.hy926 cells, proliferate
      consistently in the presence of a basal medium supplemented with bovine serum
      albumin, high-density lipoproteins, basic fibroblast growth factor, insulin, and
      transferrin. Using a new quantitative radio-RNase inhibitor assay, two distinct
      ribonucleolytic assays, and a radioimmunoassay against angiogenin, it is shown
      that RNases became apparent in media conditioned by cell monolayers. Both the
      hamster lung fibroblast and the EA.hy926 cell lines secreted larger amounts of
      RNase inhibitor-interacting factors and RNase activity than normal smooth muscle
      cells. The serum-free medium represents an alternative way to grow these cells
      and allows investigation of biosynthesis and functions of RNases in culture. It
      should be useful to identify and quantitate unambiguously specific members of the
      RNase family secreted by normal versus tumor cells in culture.

PMID- 9282318
TI  - Modulation of hepatocyte function by changing the cell shape in primary culture.
AB  - To study the role of cell shape in control of hepatocyte function, we have
      developed a system that can quantitatively control the spreading of cultured rat
      hepatocytes using poly[2-hydroxyethyl methacrylate]. When hepatocytes were
      cultured in a dish coated with high concentration of poly[2-hydroxyethyl
      methacrylate] solution, formation of stress fibers were suppressed and they
      continued to have a compact shape. In the compact-shaped hepatocytes, the ability
      to induce tyrosine aminotransferase with dexamethasone remained high for longer
      periods of time, as compared to the hepatocytes that spread following culture in
      the polystyrene dish. Conversely, the hepatocytes showed more active DNA
      synthesis when they assumed a flat shape as a result of spreading. When the
      hepatocytes that had spread following long-term culture in the polystyrene dishes
      were treated with cytochalasin to induce depolymerization of F-actin, the ability
      of the cells to induce tyrosine aminotransferase upon stimulation with
      dexamethasone improved markedly. This effect was not altered by treatment with
      actinomycin D but was completely suppressed by cycloheximide, suggesting that
      microfilaments are involved in the post-transcriptional process of tyrosine
      aminotransferase induction. Thus, there is a possibility that F-actin rather than
      cell shape might regulate cellular function in primary cultured hepatocytes.

PMID- 9282319
TI  - Stable transformation of insect cells to coexpress a rapidly selectable marker
      gene and an inhibitor of apoptosis.
AB  - We have constructed several plasmid expression vectors to express foreign genes
      in stably transformed insect cells. Unlike baculovirus-based expression vectors
      by which genes of interest are expressed transiently before lysis of the virus
      infected cells, genes can be expressed continuously over many passages in a
      stable cell line. Furthermore, the function of a gene or genes expressed in a
      stable cell line from an insect-specific promoter that is constitutively
      expressed can be studied in the absence of virus infection and viral gene
      expression. In this study, we have expressed a novel, selectable marker gene,
      puromycin acetyltransferase, under the control of the Drosophila melanogaster hsp
      70 promoter or under the control of the AcMNPV ie-1 promoter which is active in
      Spodoptera frugiperda cells in the absence of virus infection. In addition, we
      have constructed expression vectors which coexpress two genes from separate
      promoters, the pac gene which confers resistance to puromycin and a baculovirus
      gene which inhibits apoptosis, derived from Orygia pseudotsugata nuclear
      polyhedrosis virus. Both genes were expressed in stable populations of S.
      frugiperda cells in the absence of continuous drug selection.

PMID- 9282320
TI  - Kips off to Myc: implications for TGF beta signaling.
AB  - Loss of sensitivity to the negative growth regulator transforming growth factor
      beta (TGF beta) is a feature of many different tumor types and is likely involved
      in tumor progression. In some cases this loss of sensitivity to TGF beta has been
      shown to be manifest in the absence of membrane-associated TGF beta receptor
      complexes, thus preventing initiation of antiproliferative signals from the cell
      surface. In others, loss of sensitivity to TGF beta-induced inhibitory signals
      has been attributed to loss of function of intracellular effectors of TGF beta
      induced inhibitory signals due to mutation or allelic loss of effector genes and
      their products. The intracellular effectors of TGF beta inhibitory signals have
      been shown to be involved in the normal regulation of progression through the
      cell cycle, specifically during G1 phase. In this manner, elucidation of the
      mechanisms by which TGF beta inhibits cell growth not only helps us identify
      steps involved in tumor progression, but also allows us to better understand how
      cells regulate progression through the cell cycle.

PMID- 9282321
TI  - Presence of an unusually high concentration of an ubiquitinated histone-like
      protein in Trypanosoma cruzi.
AB  - The conjugation of ubiquitin to histones H2A and H2B has been established in
      higher eukaryotes and has been related to changes in chromatin organization. In
      Trypanosoma cruzi, no condensation of chromatin occurs during mitosis. In order
      to determine the presence of histone ubiquitination in T. cruzi epimastigotes,
      histones were extracted from chromatin and analyzed by three electrophoretic
      systems: acid-urea, triton-acid-urea and sodium-dodecyl-sulphate polyacrylamide
      gel. The immunochemical detection of ubiquitin-histone conjugates by Western
      blotting showed a strong reaction with a slow migrating band of M(r) 19 kDa. The
      high percentage of ubiquitin-histone conjugates present in T. cruzi chromatin may
      be related to the inability of this parasite to condense chromatin into a 30 nm
      fiber.

PMID- 9282322
TI  - Carboxyl terminus of mitosin is sufficient to confer spindle pole localization.
AB  - Mitosin is a nuclear protein of 3,113 amino acids which has been shown to
      associate with the mitotic apparatus, especially the kinetochore, during mitosis.
      In this paper we further confirmed its association with the spindle poles in
      normal monkey kidney CV1 cells by indirect immunofluorescence microscopy. When
      the carboxyl portion of mitosin containing amino acids 2,094-3,113 (named mitosin
      pTN) was stably expressed in rat fibroblast Rat2 cells using a tetracycline
      inducible system, strong spindle pole association was observed in addition to
      expected centromere localization. The same results were achieved in Chinese
      hamster ovary (CHO) cells. On the other hand, mitosin-pTC containing amino acids
      2,756-3,113 was not targeted to spindle poles. Use of the FLAG epitope [Hopp et
      al., 1988] genetically fused to each amino terminus of these mutants eliminated
      possible artifacts due to antibody cross-reaction, since the spindle pole
      localization of wild-type mitosin was confirmed with a FLAG-tagged mutant by an
      antibody (anti-FLAG M2 monoclonal antibody) irrelevant to antibodies to mitosin.
      Our data also suggested a possible interaction of mitosin with the spindle
      microtubules. Interaction of mitosin with the major parts of the mitotic
      apparatus further implies an important role in mitosis.

PMID- 9282323
TI  - Regulation of adenylyl cyclase isoforms by N-alkanols.
AB  - We examined the effect of n-alkanols on adenylyl cyclase isoforms (types II and
      V) overexpressed in insect cells. Ethanol stimulated the type II isoform but not
      the type V isoform. Ethanol stimulated type II adenylyl cyclase greater than GTP
      gamma S, and the treatment of the membrane with GDP beta S or cholera toxin did
      not affect this stimulation. Other n-alkanols inhibited type V adenylyl cyclase
      activity in proportion to their lipophilic potency. In contrast, type II adenylyl
      cyclase was stimulated by weakly lipophilic n-alkanols and inhibited by strongly
      lipophilic n-alkanols. When solubilized membranes and purified preparations were
      used, all the n-alkanols inhibited type II adenylyl cyclase. Our data suggest
      that n-alkanols regulated adenylyl cyclase isoform-dependently. Stimulation of
      the type II isoform was independent from the interaction with Gs alpha but
      required the presence of an intact membrane structure. Our study may provide
      another step to understanding how membrane protein subtypes are differentially
      regulated by n-alkanols.

PMID- 9282324
TI  - Hybrid structural analogues of 1,25-(OH)2D3 regulate chondrocyte proliferation
      and proteoglycan production as well as protein kinase C through a nongenomic
      pathway.
AB  - 1,25-(OH)2D3 and 24,25-(OH)2D3 mediate their effects on chondrocytes through the
      classic vitamin D receptor (VDR) as well as through rapid membrane-mediated
      mechanisms which result in both nongenomic and genomic effects. In intact cells,
      it is difficult to distinguish between genomic responses via the VDR and genomic
      and nongenomic responses via membrane-mediated pathways. In this study, we used
      two hybrid analogues of 1,25-(OH)2D3 which have been modified on the A-ring and
      C,D-ring side chain (1 alpha-(hydroxymethyl)-3 beta-hydroxy-20-epi-22-oxa-26,27
      dihomo vitamin D3 (analogue MCW-YA = 3a) and 1 beta-(hydroxymethyl)-3 alpha
      hydroxy-20-epi-22-oxa-26,27-dihomo vitamin D3 (analogue MCW-YB = 3b) to examine
      the role of the VDR in response of rat costochondral resting zone (RC) and growth
      zone (GC) chondrocytes to 1,25-(OH)2D3 and 24,25-(OH)2D3. These hybrid analogues
      are only 0.1% as effective in binding to the VDR from calf thymus as 1,25
      (OH)2D3. Chondrocyte proliferation ([3H]-thymidine incorporation), proteoglycan
      production ([35S]-sulfate incorporation), and activity of protein kinase C (PKC)
      were measured after treatment with 1,25-(OH)2D3, 24,25-(OH)2D3, or the analogues.
      Both analogues inhibited proliferation of both cell types, as did 1,25-(OH)2D3
      and 24,25-(OH)2D3. Analogue 3a had no effect on proteoglycan production by GCs
      but increased that by RCs. Analogue 3b increased proteoglycan production in both
      GC and RC cultures. Both analogues stimulated PKC in GC cells; however, neither
      3a nor 3b had an effect on PKC activity in RC cells. 1,25-(OH)2D3 and 3a
      decreased PKC in matrix vesicles from GC cultures, whereas plasma membrane PKC
      activity was increased, with 1,25-(OH)2D3 having a greater effect. 24,25-(OH)2D3
      caused a significant decrease in PKC activity in matrix vesicles from RC
      cultures; 24,25-(OH)2D3, 3a, and 3b increased PKC activity in the plasma membrane
      fraction, however. Thus, with little or no binding to calf thymus VDR, 3a and 3b
      can affect cell proliferation, proteoglycan production, and PKC activity. The
      direct membrane effect is analogue-specific and cell maturation-dependent. By
      studying analogues with greatly reduced affinity for the VDR, we have provided
      further evidence for the existence of a membrane receptor(s) involved in
      mediating nongenomic effects of vitamin D metabolites.

PMID- 9282325
TI  - Substance P stimulates vascular endothelial cellular reducing capacity in the
      presence of insulin and human plasma factors.
AB  - Substance P (SP) is an important tachykinin in vascular wall biology. In previous
      studies [Villablanca et al. (1994): Circ Res 75:1113-1120], the authors have
      demonstrated that SP is a stimulus for endothelial cell growth and proliferation
      in serum-free culture conditions with cell quiescent in the G0-G1 phase of the
      cell cycle. As mitogenic and metabolic activity may interrelate, the purpose of
      this study was to determine the effects of the vasoactive perivascular
      neuropeptide SP on changes in the metabolic function of endothelial cells, and to
      characterize the response, by studying cellular reducing capacity in aortic
      vascular endothelial cells. In addition, interactions between SP and other growth
      factors (insulin and non-platelet plasma factors) were investigated and compared
      to the responses to SP alone. Metabolic effects were determined by evaluating
      cellular reducing capacity by the conversion of (3-[4,5-dimethylthiazole-2-yl]
      2,5-diphenyltetrazolium bromide) to formazan (the MTT assay). The findings
      demonstrated that SP alone (10 pg/ml-25 micrograms/ml) inhibited cellular
      reducing capacity in vascular endothelial cells. In contrast, SP in the presence
      of insulin (10 micrograms/ml) stimulated endothelial reducing capacity, as
      compared to SP alone, by twofold on average. The effect of SP and insulin was
      additive at < or = 0.001 microgram/ml SP, and synergistic at SP concentrations
      ranging within 0.01-1.0 microgram/ml. SP in the presence of human platelet-poor
      plasma (HPPP, 5%) stimulated endothelial reducing capacity, as compared to SP
      alone, by threefold on average. The effect of SP and HPPP was additive at < or =
      0.01 microgram/ml SP and synergistic at SP concentrations of 0.1-25
      micrograms/ml. Lastly, SP in the presence of insulin and HPPP stimulated
      endothelial metabolic activity, as compared to SP alone, by 14-fold on average.
      An additive response to SP, insulin, and HPPP was observed at the lowest SP
      concentration studied (10 pg/ml). At all other SP concentrations studied (0.0001
      25 micrograms/ml), the responses to insulin, HPPP, and SP were synergistic. Our
      studies indicate that the vasoactive neuropeptide substance P may synergize with
      insulin and HPPP in regulating endothelial cell metabolism. In addition, our
      findings suggest that the mechanisms by which SP stimulates cellular metabolism
      are different from the mechanisms by which it stimulates cell growth.

PMID- 9282326
TI  - Electromagnetic field exposure induces rapid, transitory heat shock factor
      activation in human cells.
AB  - Stimulation of human promyelocytic HL60 cells by a 60Hz magnetic field at normal
      growth temperatures results in heat shock factor 1 activation and heat shock
      element binding, a sequence of events that mediates the stress-induced
      transcription of the stress gene HSP70 and increased synthesis of the stress
      response protein hsp70kD. Thus, the events mediating the electromagnetic field
      stimulated stress response appear to be similar to those reported for other
      physiological stresses (e.g., hyperthermia, heavy metals, oxidative stress) and
      could well be the general mechanism of interaction of electromagnetic fields with
      cells.

PMID- 9282327
TI  - Reciprocal modulation between Sp1 and Egr-1.
AB  - Many ubiquitously expressed genes, including oncogenes, lack a proximal TATA or
      CAAT box but have a region of G + C-rich sequences that appears to replace the
      usual promoter initiation site. The zinc-finger protein Sp1 is one of the
      prevalent activators of these genes. The Egr-1 zinc-finger protein has a similar
      binding site and if the two sites occur in the same region, a variety of
      activation or inhibitory responses may be obtained. We show that competition
      between the two factors for overlapping sites on growth-promoting genes could
      explain why the overexpression of Egr-1 suppresses transformed growth in a number
      of cell types [Huang et al. (1995): Cancer Res 55:5054-5062; Huang et al. (1997):
      Int J Cancer]. We demonstrate here that Egr-1 and Sp1 can bind to the same G + C
      rich sites and that Egr-1 can displace Sp1 and hence inhibit its activity. We
      measured the responses of synthetic consensus binding sites and natural promoter
      sequences linked to a reporter gene and showed that Egr-1 inhibited the
      activation of transcription by Sp1 on overlapping Sp1/Egr-1 sites. In contrast,
      Sp1 activity could be augmented by Egr-1 at nonoverlapping sites in the Egr-1
      gene promoter, in transient reporter gene studies in Drosophila SL2 cells. In
      addition, over-expression of exogenous Sp1 in mammalian cells, also leads to
      increased Egr-1 protein expression, which further inhibits Sp1 transactivation of
      numerous genes. Therefore, we can account for some of the complex responses of G
      + C-rich enhancer/promoters by a form of "facilitated inhibition" of Sp1 by Egr-1
      at overlapping sites.

PMID- 9282328
TI  - Epitope conservation and immunohistochemical localization of the guanylin/stable
      toxin peptide receptor, guanylyl cyclase C.
AB  - The heat-stable enterotoxins (ST) are a family of cysteine-rich low-molecular
      weight peptides produced by pathogenic bacteria, and are one of the major causes
      of watery diarrhea all over the world. These toxins mediate their action by
      binding to an intestinal cell surface receptor that is a membrane-associated
      guanylyl cyclase (GCC). This receptor also serves as the receptor for the
      recently characterised endogenous ligand, guanylin. We have expressed various
      domains of the receptor in Escherichia coli and used purified proteins for the
      generation of both polyclonal and monoclonal antibodies. While polyclonal
      antibodies were able to partially inhibit ST binding to the native receptor
      present in the T84 human colonic cell line, GCC:B10 monoclonal antibody did not
      interfere with ligand binding. Western blot analysis, using membranes prepared
      from human colonic T84 cells, detected two bands of size 160 and 140 kDa,
      representing alternately glycosylated forms of the receptor. Using the
      recombinant proteins, we could map the epitope of GCC:B10 monoclonal antibody to
      the intracellular domain of the receptor. We used the antibody to localize the
      receptor throughout the rat intestine, and in the porcine and bonnet monkey
      colon. We could detect receptor expression in the villus and the crypts of the
      duodenum, jejunum, ileum, and caecum, and in the crypts of the colon. Receptor
      expression was observed in cells that had earlier been shown to express cGMP
      dependent kinase, but not the cystic fibrosis transmembrane regulator, a known
      downstream target of cGMP/G-kinase, which suggests that GCC/ cGMP could regulate
      additional cellular signal transduction machinery.

PMID- 9282329
TI  - Cell cycle-dependent modifications in activities of pRb-related tumor suppressors
      and proliferation-specific CDP/cut homeodomain factors in murine hematopoietic
      progenitor cells.
AB  - The histone H4 gene promoter provides a paradigm for defining transcriptional
      control operative at the G1/S phase transition point in the cell cycle.
      Transcription of the cell cycle-dependent histone H4 gene is upregulated at the
      onset of S phase, and the cell cycle control element that mediates this
      activation has been functionally mapped to a proximal promoter domain designated
      Site II. Activity of Site II is regulated by an E2F-independent mechanism
      involving binding of the oncoprotein IRF2 and the multisubunit protein HiNF-D,
      which contains the homeodomain CDP/cut, CDC2, cyclin A, and the tumor suppressor
      pRb. To address mechanisms that define interactions of Site II regulatory factors
      with this cell cycle control element, we have investigated these determinants of
      transcriptional regulation at the G1/S phase transition in FDC-P1 hematopoietic
      progenitor cells. The representation and activities of histone gene regulatory
      factors were examined as a function of FDC-P1 growth stimulation. We find
      striking differences in expression of the pRb-related growth regulatory proteins
      (pRb/p105, pRb2/p130, and p107) following the onset of proliferation. pRb2/p130
      is present at elevated levels in quiescent cells and declines following growth
      stimulation. By contrast, pRb and p107 are minimally represented in quiescent FDC
      P1 cells but are upregulated at the G1/S phase transition point. We also observe
      a dramatic upregulation of the cellular levels of pRb2/p130-associated protein
      kinase activity when S phase is initiated. Selective interactions of pRb and p107
      with CDP/cut are observed during the FDC-P1 cell cycle and suggest functional
      linkage to competency for DNA binding and/or transcriptional activity. These
      results are particularly significant in the context of hematopoietic
      differentiation where stringent control of the cell cycle program is requisite
      for expanding the stem cell population during development and tissue renewal.

PMID- 9282331
TI  - Induction of intracellular ceramide by interleukin-1 beta in oligodendrocytes.
AB  - The sphingomyelin pathway has been implicated in mediating the effect of several
      extracellular agents leading to important biochemical and cellular changes. The
      aim of this investigation is to study interleukin-1 beta (IL-1 beta) signaling in
      oligodendrocytes. For this purpose, the CG4 oligodendrocyte cells were
      differentiated and incubated with IL-1 beta. This treatment induced a time- and
      dose-dependent increase of the endocellular ceramide. To mimic the effect of the
      elevation of endogenous ceramide, the CG4 cells were treated with the ceramide
      analogue C2-ceramide. Cell survival, measured with the MTT assay, showed that, by
      increasing the concentration of ceramide, up to 40% of CG4 cells were dying
      within 6 h, similar data were obtained with the primary differentiated
      oligodendrocytes. Condensation of chromatin, nuclear fragmentation, and formation
      of apoptotic bodies indicated that apoptosis was the cause of death.
      Surprisingly, long-term exposure (72 h) to increasing concentrations of IL-1
      beta, which increases intracellular ceramide, did not induce oligodendroglial
      cell death. These results show that an increase of intracellular ceramide is not
      sufficient to induce apoptosis in oligodendrocytes and that IL-1 beta signaling
      through the ceramide pathway in these cells can mediate functions other than
      programmed cell death.

PMID- 9282330
TI  - Evidence for inhibition of MyEF-2 binding to MBP promoter by MEF-1/Pur alpha.
AB  - Myelin basic protein (MBP) is a major component of the myelin sheath whose
      production is developmentally controlled during myelinogenesis. Earlier studies
      have indicated that programmed expression of the MBP gene is regulated at the
      level of transcription. Evidently, the MB1 regulatory motif located between
      nucleotides -14 to -50 plays an important role in transcription of the MBP
      promoter in both in vivo systems. The MB1 element contains binding sites for the
      activator protein MEF-1/Pur alpha and the repressor protein MyEF-2. In this study
      we use bandshift assays with purified MEF-1/Pur alpha and MyEF-2 and demonstrate
      that binding of MyEF-2 to its target sequence is inhibited by MEF-1/Pur alpha.
      Under similar conditions, MyEF-2 enhances the association of MEF-1/Pur alpha with
      MB1 DNA. MEF-1/Pur alpha binds to MB1 in mono- and dimeric forms. Inclusion of
      MyEF-2 in the binding reaction increases the dimeric association of MEF-1/Pur
      alpha with the MB1 sequence. The use of MEF-1/Pur alpha variants in the bandshift
      assay suggests that two distinct regions of this protein may be involved in its
      binding to the MB1 sequences, and its ability to block MyEF-2 interaction with
      the MB1 sequence. Based on previous studies on the programmed expression of MEF
      1/Pur alpha and MyEF-2 during myelination and the current findings on their
      interplay for binding to the MB1 motif, a model is proposed for their involvement
      in transcriptional regulation of the MBP gene during the course of brain
      development.

PMID- 9282332
TI  - Development and characterization of a conditionally immortalized human
      osteoblastic cell line stably transfected with the human androgen receptor gene.
AB  - Androgens have significant beneficial effects on the skeleton. However, studies
      on the effects of androgens on osteoblasts are limited due to the absence of
      appropriate model systems that combine completeness of the osteoblastic
      phenotype, rapid proliferation rate, and stable expression of the androgen
      receptor (AR). Thus, we stably transfected the conditionally immortalized human
      fetal osteoblastic cell line (hFOB) with the human wild-type AR (hAR) cDNA.
      Compared to nontransfected hFOB cells, constitutive hAR mRNA expression in three
      independent hAR-transfected hFOB clones (hFOB/AR) was 15-fold higher in hFOB/AR
      16, 62-fold higher in hFOB/AR-2, and 72-fold higher in hFOB/AR-6 cells,
      respectively, as assessed by semiquantitative reverse transcriptase-polymerase
      chain reaction (RT-PCR). Detectable constitutive levels of hAR mRNA by Northern
      blot analysis were present in hFOB/AR-2 and hFOB/AR-6 cells, but not in hFOB/AR
      16 or hFOB cells, respectively. Treatment with 5 alpha-dihydrotestosterone (5
      alpha-DHT) (10(-8) M) for 24 h did not alter hAR mRNA steady state levels in the
      hFOB/AR cell lines. Nuclear binding studies demonstrated 152 +/- 73 (mean +/-
      SEM) functional hARs/nucleus in non-transfected hFOB cells, 3,940 +/- 395
      functional hARs/nucleus in hFOB/AR-2 cells, and 3,987 +/- 823 hARs/nucleus in
      hFOB/AR-6 cells, respectively. Treatment with 5 alpha-DHT increased the
      expression of a transiently transfected androgen response element-chloramphenicol
      acetyltransferase (ARE-CAT) reporter construct in hFOB/AR-6 cells in a dose- and
      time-dependent manner; no such effect was observed in transiently transfected
      hFOB cells lacking exogenously transfected hARs. Moreover, 5 alpha-DHT-induced
      ARE-CAT expression was inhibited by the selective androgen receptor antagonist,
      hydroxyflutamide. In summary, we have developed and characterized androgen
      responsive osteoblastic cell lines derived from normal human fetal bone that
      express physiological levels of functional hARs. These cell lines should provide
      a suitable model for further studies on the effects of androgens on osteoblast
      function, including the identification of potential androgen-regulated growth
      factors and cytokines.

PMID- 9282333
TI  - Sensitive induction of apoptosis in breast cancer cells by a novel 1,25
      dihydroxyvitamin D3 analogue shows relation to promoter selectivity.
AB  - The biologically active form of vitamin D3, the nuclear hormone 1 alpha,25
      dihydroxyvitamin D3 (VD), is an important regulator of cellular growth,
      differentiation, and death. The hormone mediates its action through the
      activation of the transcription factor VDR, which is a member of the superfamily
      of nuclear receptors. In most cases the ligand-activated VDR is found in complex
      with the retinoid X receptor (RXR) and stimulates gene transcription mainly from
      VD response elements (VDREs) that are formed by two hexameric core binding motifs
      and are arranged either as a direct repeat spaced by three nucleotides (DR3) or
      as an inverted palindrome spaced by nine nucleotides (1P9). The two VD analogues
      CB1093 and EB1089 are both very potent inhibitors of the proliferation of MCF-7
      cultured breast cancer cells displaying approximately 100-fold lower IC50 values
      (0.1 nM) than the natural hormone. In addition, CB1093 is even more potent in
      vivo than EB1089 in producing regression of experimental mammary tumors.
      Moreover, both VD analogues induce apoptosis in MCF-7 cells, but CB1093 is
      effective at concentrations approximately 10-fold lower than EB1089. In
      accordance, the reduction of Bcl-2 protein expression showed CB1093 to be more
      potent than EB1089. This suggests that the antiproliferative effect of CB1093 may
      be related mainly to its apoptosis inducing effect, whereas EB1089 may
      preferentially have effects on growth arrest. EB1089 is known to result in a
      selectivity for the activation of IP9-type VDREs, whereas CB1093 shows a
      preference for the activation of DR3-type VDREs. This promoter selectivity
      suggests that the effects of VD and its analogues on growth arrest and the
      induction of apoptosis may be mediated by different primary VD responding genes.
      In conclusion, CB1093 was found to be a potent inhibitor of rat mammary tumor
      growth in vivo. CB1093 also displayed a high potency in vitro in the induction of
      apoptosis, a process that may be linked to a promoter selectivity for DR3-type
      VDREs.

PMID- 9282334
TI  - Hormonal, secretory and morphological alterations in gastric mucosa in the course
      of Helicobacter pylori eradication in patients with duodenal ulcer and non-ulcer
      dyspepsia.
AB  - Changes in endocrine and secretory functions and in the morfology of gastric
      mucosa in the course of quadruple H. pylori eradication regimen in 50 H. pylori
      positive patients: 25 with duodenal ulcer (DU) and 25 with non ulcer dyspepsia
      (NUD) were studied and compared to 10 healthy controls. Therapy resulted in ulcer
      healing in all DU patients and in 92% eradication of H. pylori in both groups of
      patients-DU and NUD. In DU and NUD patients in the course of eradication
      significant decrease in plasma gastrin was observed. Somatostatin concentration
      in gastric juice increased significantly in DU patients after anti-H. pylori
      therapy. EGF in gastric content of DU and NUD patients has risen statistically
      significantly in the course of H. pylori eradication. Gastric acid output and
      volume flow decreased insignificantly in both groups. The elimination of H.
      pylori from gastric mucosa in both DU and NUD patients led to significant
      decrease in the density and activity of gastritis.

PMID- 9282335
TI  - Microchipping: the evolution of a global standard.

PMID- 9282336
TI  - What is your diagnosis? Multiple myeloma.

PMID- 9282338
TI  - Effect and mechanisms of the anti-prolactin drug cabergoline on pseudopregnancy
      in the bitch.
AB  - A potent anti-prolactin drug, cabergoline, administered orally for five days, was
      clinically successful in treating three different clinical manifestations of
      pseudopregnancy in referred bitches. The clinical conditions treated were
      categorised as standard pseudopregnant bitches (n = 8), those previously
      unsuccessfully treated with hormones (n = 10) and those which had behavioural
      pseudopregnancy following ovariohysterectomy (n = 8). The number of bitches whose
      owners reported a 'good' response was seven out of eight, six out of 10 and six
      out of eight, respectively. There were very few side effects in that only one
      bitch vomited following treatment. The clinical response did not necessarily
      appear to be related to an alteration in circulating prolactin concentrations,
      suggesting that the drug may have a direct effect on the tissues as well as in
      most cases reducing the plasma prolactin concentrations.

PMID- 9282339
TI  - Reference ranges for gastrointestinal transit of barium-impregnated polyethylene
      spheres in healthy cats.
AB  - Commercial barium-impregnated polyethylene spheres (BIPS) were administered to 12
      healthy adult cats according to the manufacturer's instructions (30 small BIPS
      and 10 large BIPS to each cat) together with 60 g of a canned food. Radiographs
      were taken at hourly intervals until seven hours after feeding, and then at
      eight, 10, 12, 14, 17, 23 and 30 hours or until all the BIPS had left the stomach
      and at least 50 per cent had entered the colon. Six cats were sedated immediately
      after being fed the BIPS and six cats remained unsedated. For small BIPS (1.5 mm
      diameter), the gastric transit time (first exit of BIPS from the stomach) in the
      sedated cats had a median of 6 hours (range 3 to 8) and in the unsedated cats a
      median of 2.5 hours (range 2 to 6). Values for other transit times were not
      significantly different between the two groups, and the pooled data revealed a
      median 50 per cent gastric emptying time of 6.4 hours (range 2.5 to 10.9), a
      complete gastric emptying time of 12 hours (range 6 to 27), an orocaecal transit
      time (first appearance of BIPS in the colon) of 6.5 hours (range 4.0 to 12.0) and
      a 50 per cent orocaecal transit time of 8.8 hours (range 4.6 to 12.8). The
      gastrointestinal transit of large BIPS (5 mm diameter) was significantly
      correlated with the passage of small BIPS but, except for the complete gastric
      emptying time, was significantly slower.

PMID- 9282337
TI  - Visual disturbance: where do I look?
AB  - Visual disturbances often signal serious ophthalmic disease. Comprehensive
      general medical and ophthalmic histories are most helpful. Information about the
      animal's vision, based on its performance in familiar and unfamiliar
      environments, should be obtained from the owner. As bilateral involvement and
      visual disturbances are often associated with systemic diseases, a complete
      physical examination is indicated. The ophthalmic examination consists of a
      series of diagnostic procedures to isolate and define the ophthalmic disorder.
      Several clinical tests can be performed easily in the examination room, including
      the light-induced pupillary reflex, the dazzle or photic reflex, the menace
      reflex, the obstacle course test and, if indicated, the flash electroretinogram,
      the visual evoked response and, recently, the pattern electroretinogram.
      Ophthalmic diseases that produce visual disturbances in dogs often affect the
      cornea, aqueous pathways, lens and ocular fundus; in cats, they usually affect
      the uveal tract and are associated with serious systemic diseases. Orbital
      diseases are not usually associated with visual disturbance unless the optic
      nerve is involved. Corneal diseases and cataract formation that involve the
      visual axis and pupillary aperture often cause visual disturbance. Inflammations
      of the Iris and ciliary body can produce both acute and long-term visual
      disturbance and even blindness. Diseases of the retina and optic nerve usually
      present as visual disturbances in the absence of pain.

PMID- 9282340
TI  - Metacarpal and metatarsal fractures in dogs.
AB  - Metacarpal fractures were more common than metatarsal fractures in this
      retrospective study of 37 dogs. Fractures of one metacarpal or metatarsal bone
      occurred in 24 per cent of the dogs, two metacarpal bones in 16 per cent, three
      metacarpal or metatarsal bones in 19 per cent, and four metacarpal or metatarsal
      bones in 41 per cent. Eighty-seven per cent of the dogs with fractures of four
      bones had fracture displacement or malalignment of at least one digit.
      Progressive fracture healing usually occurred irrespective of stabilisation
      method. For malaligned fractures, however, external coaptation did not
      consistently improve alignment. Fracture alignment was consistently improved by
      open reduction and internal fixation of acute fractures with bone plates.
      Fractures of four bones occurred most often in the distal metacarpus as opposed
      to the proximal metatarsus. Therefore, open reduction and internal fixation may
      be more commonly indicated for severe metacarpal fractures, because fracture
      displacement or axial malalignment was significantly associated with fractures of
      the mid or distal regions of the metacarpus or metatarsus (P = 0.052).

PMID- 9282341
TI  - Heritability of epileptic seizures in the Belgian tervueren.
AB  - Survey data were collected on the incidence of epileptic seizures in 997 Belgian
      tervuerens. The heritability of this disorder was estimated as 0.77 (with a 95
      per cent confidence interval spanning from 0.65 to 0.88) using a Bayesian
      analysis in an ordered categorical threshold model. Single locus models do not
      appear adequate as an explanation for this inherited seizure disorder. The high
      heritability estimate suggests that breeders can wage a successful battle against
      this disorder by breeding unaffected individuals, particularly those from
      families with no history of seizures.

PMID- 9282342
TI  - Normative auditory brainstem response data for bone conduction in the dog.
AB  - Auditory brainstem response (ABR) is a valuable tool for the diagnosis of hearing
      disorders in dogs, but is hampered by the lack of published normative data. The
      aim of the present study was to obtain normative data for bone conduction,
      without masking, under clearly defined conditions. Subjects comprised 20
      Dalmatians and 20 Jack Russell terriers. Two methods were investigated: holding
      the bone vibrator against the head by hand or by applying a 500 g weight. The
      results revealed no difference in hearing threshold between the two breeds or for
      the two methods of applying the bone vibrator to the head. The mean hearing
      threshold was close to 0 decibels re normal hearing level (dB nHL), which is the
      biological norm for humans. Hence, bone conduction thresholds can be used for
      confirmation of conductive hearing impairment in the dog, in the same way as in
      humans.

PMID- 9282345
TI  - Special neutering campaign.

PMID- 9282343
TI  - Cranioplasty after en bloc resection of calvarial chondroma rodens in two dogs.
AB  - The clinical features of chondroma rodens in two dogs and the treatment using
      radiation therapy, en bloc resection of the tumours and cranioplasties with a
      bone allograft (case 1) and a polymethylmethacrylate implant (case 2) are
      described. The dogs were still alive with no local recurrence of the tumours 30
      and 18 months, respectively, after surgery. En bloc resection and calvarial
      reconstruction in the treatment of chondroma rodens are discussed.

PMID- 9282346
TI  - The new ISO standard. Which microchip should I use?

PMID- 9282344
TI  - Tetraparesis due to vertebral physeal fracture in an adult dog with congenital
      hypothyroidism.
AB  - A four-year-old male affenpinscher was referred for evaluation of hindlimb
      weakness that had progressed to tetraparesis over a period of four weeks.
      Neurological examination was suggestive of a cervical spinal cord lesion.
      Radiographic examination revealed diffuse skeletal immaturity with open physes
      and epiphyseal dysplasia in long bones and vertebrae, consistent with a diagnosis
      of congenital hypothyroidism. Total and free serum T4 concentrations were very
      low, indicative of hypothyroidism. Survey radiographs of the cervical spine
      revealed a dorsally displaced Salter-Harris type I fracture of the cranial
      portion of the fourth cervical vertebra with the endplate present in the
      vertebral canal. Although signs of transverse myelopathy are uncommon in dogs
      with congenital hypothyroidism, they may be associated with either intervertebral
      disc protrusion or endplate displacement into the vertebral canal secondary to
      the epiphyseal abnormalities associated with congenital hypothyroidism.

PMID- 9282347
TI  - Salmonellosis.

PMID- 9282348
TI  - The effect of ultrasound frame rate on perfluorocarbon-exposed sonicated dextrose
      albumin microbubble size and concentration when insonifying at different flow
      rates, transducer frequencies, and acoustic outputs.
AB  - The purpose of this article was to compare the effects of 1 and 30 Hz frame rates
      on perfluorocarbon-exposed sonicated dextrose albumin microbubble size and
      concentration in a flow cell containing either saline or blood at 37 degrees C.
      Microbubble size and concentration of perfluorocarbon-exposed sonicated dextrose
      albumin were measured after insonation at different acoustic outputs, transducer
      frequencies, and flow rates with the use of the two different frame rates and
      compared with no ultrasound exposure. At 2.0 MHz insonation frequency,
      microbubble concentration was significantly reduced with the use of a 30 Hz frame
      rate and peak negative pressures of 1.1 megaPascal (mPa). This destruction did
      not occur when using a lower acoustic output, a 1 Hz frame rate, or when flow
      rate was increased to 100 cc/min. One-hertz frame rates at 2.0 MHz resulted in a
      significantly larger mean microbubble size than 30 Hz or no ultrasound in both
      saline and blood, which was in part due to selective destruction of smaller
      microbubbles. These findings indicate that 30 Hz frame rates destroy
      perfluorocarbon-exposed sonicated dextrose albumin microbubbles only at higher
      diagnostic acoustic outputs. A 1 Hz frame rate prevents this destruction,
      especially destruction of larger (> 5.0 microns) microbubbles.

PMID- 9282349
TI  - Benefits of reducing the cardiac cycle-triggering frequency of ultrasound imaging
      to increase myocardial opacification with FSO69 during fundamental and second
      harmonic imaging.
AB  - BACKGROUND: Recent work has shown significant enhancement in myocardial contrast
      intensity with brief ultrasound pulsing gated to a discrete portion of the
      cardiac cycle over conventional 30 Hz imaging. We hypothesized that limiting
      ultrasound imaging to less than every cardiac cycle would further intensity the
      myocardial echo-contrast effect. We therefore sought to determine the best
      pulsing frequency for ultrasound imaging to achieve optimal myocardial perfusion
      after the intravenous administration of FSO69 using fundamental and second
      harmonic imaging. METHODS AND RESULTS: In 13 male mongrel dogs, myocardial
      contrast opacification was determined while varying the cardiac cycle-triggering
      frequency of ultrasound imaging after intravenous injections of FSO69. Resulting
      myocardial echo-contrast intensities with a cardiac cycle-triggering frequency of
      every beat during end-diastole were compared with those with a cardiac cycle
      triggering frequency of every third and fifth beat. Myocardial opacification,
      measured by background-subtracted peak intensity and visual scoring, was
      significantly greater when ultrasound imaging was triggered to every third and
      fifth beats compared with every beat. These benefits were seen with imaging in
      both the fundamental and second harmonic modes. Optimal myocardial opacification
      with FSO69 was achieved with injections as low as 0.1 ml, a dose that produced
      significant acoustic shadowing in only 24% of the injections. The degree of
      myocardial opacification was not significantly affected when the images were
      acquired during end-systole or end-diastole. CONCLUSIONS: Electrocardiogram-gated
      ultrasound imaging to every third or fifth cardiac cycle greatly improves
      myocardial opacification compared with imaging each cardiac cycle. This benefit
      was increased twofold to threefold with the use of second harmonic imaging as
      compared with fundamental imaging.

PMID- 9282350
TI  - Improved transvalvular continuous-wave Doppler signal intensity after intravenous
      Albunex injection in patients with prosthetic aortic valves.
AB  - A lung-crossing contrast agent, sonicated albumin (Albunex), has been reported to
      enhance left-sided Doppler signals in patients with native valvular diseases. The
      purpose of this study was to clarify the ability of Albunex to enhance
      transvalvular Doppler signals in patients with prosthetic aortic valves. Forty
      five consecutive patients were studied after they underwent aortic valve
      replacement. Transvalvular flow signals were recorded from the apical long-axis
      view with the use of continuous-wave Doppler echocardiography before and after
      intravenous injection of Albunex (0.04 to 0.08 ml/kg). Continuous-wave Doppler
      signal quality was graded as follows: 1, none; 2, poor; 3, suboptimal; and 4,
      optimal. RESULTS: Grade 4 continuous-wave Doppler signal could be detected in 64%
      of the cases (29 of 45). After contrast injection, continuous-wave Doppler signal
      quality improved in all, and grade 4 continuous-wave Doppler signal could be
      detected in 93% (0.04 ml/kg) and 100% (0.08 ml/kg), respectively. The
      transvalvular maximal velocities derived from contrast-enhanced, continuous-wave
      Doppler signals were well correlated with the highest available unenhanced.
      Doppler maximal velocities (y = 0.90x + 0.27, r = 0.93, p < 0.01, standard error
      of estimate = 0.08 m/sec). CONCLUSION: Intravenous Albunex injection improves
      transvalvular continuous-wave Doppler signal intensity in patients with
      prosthetic aortic valves.

PMID- 9282351
TI  - Understanding continuous-wave Doppler signal intensity as a measure of
      regurgitant severity.
AB  - Continuous-wave Doppler signal intensity is commonly expected to reflect the
      severity of mitral regurgitation. Physical principles predict that alignment of
      the imaging beam, flow velocity, and turbulence can also be important or even
      dominant determinants of continuous-wave Doppler signal intensity. The
      reliability of tracking regurgitant severity with continuous-wave Doppler signal
      intensity was assessed in vitro with varying volume, velocity, turbulence, and
      beam alignment. The conditions wherein continuous-wave Doppler signal intensity
      increased with regurgitant volume were specific but poorly predictable
      combinations of orifice size, flow volume, and perfect beam alignment. Under
      other conditions flow velocity and turbulence effects dominated, and continuous
      wave Doppler signal intensity did not reflect changing regurgitant volume.
      Continuous-wave Doppler signal intensity-based impressions of regurgitant
      severity may be unreliable and even misleading under some circumstances.

PMID- 9282352
TI  - In vitro evaluation of forward and reverse volumetric flow across a regurgitant
      aortic valve using Doppler power-weighted mean velocities.
AB  - To determine the accuracy of using power-weighted mean velocities for
      quantitating volumetric flow across a cardiac valve, we equipped pulsatile flow
      tank systems with a 25 mm porcine or a 27 mm mechanical valve with various sizes
      of regurgitant orifices. Forward and reverse volumetric flows were measured over
      a range of hemodynamic conditions using two insonating angles (0 and 45 degrees).
      Pulsed Doppler power-weighted mean velocity measurements were obtained
      simultaneously with electromagnetic or ultrasonic transit-time probe
      measurements. For the porcine valve, Doppler measurements correlated well with
      electromagnetic flow measurements for all (r = 0.75 to 0.97, p < 0.05) except the
      smallest (2.7 mm) orifice (r = 0.19). For the mechanical valve, power-weighted
      mean velocity measurements correlated well with ultrasonic transit-time
      measurements for each hemodynamic condition defined by pulse rate, mean arterial
      pressure, and insonating angle (r = 0.93 to 0.99, p < 0.01), but equations varied
      unpredictably. Thus, although power-weighted mean velocity volumetric flow
      measurements correlate well with flow probe measurements, equations vary widely
      as hemodynamic conditions change. Because of this variation, power-weighted mean
      velocity data are not useful for quantitation of volumetric flow across a cardiac
      valve at this time. Further investigation may show how different hemodynamic
      conditions affect power-weighted mean velocity measurements of volumetric flow.

PMID- 9282353
TI  - Normal echocardiographic characteristics of the Sorin Bicarbon bileaflet
      prosthetic heart valve in the mitral and aortic positions.
AB  - Doppler echocardiographic characteristics of normally functioning Sorin Bicarbon
      prostheses were prospectively assessed in 226 consecutive patients (135 male and
      91 female patients, mean age 61 +/- 10 years) with 233 valves in the mitral (n =
      67) and aortic (n = 166) positions whose function was considered normal by
      clinical and echocardiographic evaluation. Patterns of "normal" transprosthetic
      leakage were assessed with transthoracic echocardiography in all valves and with
      transesophageal echocardiography in six selected mitral valve prostheses. For the
      mitral valve prostheses, we found that peak and mean gradient, as well as
      pressure half-time, were not significantly different in either the 25 or the 31
      mm valves (median values from 15 to 10 mm Hg, from 4 to 4 mm Hg, and from 70 to
      83 ms; p = Not significant for all). On transthoracic study, 12 patients (17%)
      with a Sorin Bicarbon valve in the mitral position showed minimal transprosthetic
      leakage. On transesophageal study, all patients showed a transprosthetic leakage
      whose spatial distribution had a complex pattern: in planes orthogonal to the
      leaflet axis, two to four jets arising from the hinge points and converging
      toward the center of the valve plane could be visualized; in planes parallel to
      the leaflet axis, there were three jets, the two lateral ones diverging and the
      central one perpendicular to the valve plane. For the aortic valve prostheses,
      there was a significant decrease in transprosthetic gradients and an increase in
      effective orifice areas as prosthesis size increased. Peak and mean gradients
      decreased from a median value of 25 and 13 mm Hg in the 19 mm valves to 9 and 5
      mm Hg in the 29 mm valves, respectively. Effective prosthetic valve area
      calculated with the continuity equation increased from a median value of 0.97 cm2
      for the 19 mm size valves to 3.45 cm2 for the 29 mm size. With analysis of
      variance, effective prosthetic aortic valve area differentiated various valve
      sizes (F = 40.9, p < 0.0001) better than peak (F = 10.3, p < 0.0001) or mean (F =
      8.04, p < 0.0001) gradients alone did. Furthermore, effective prosthetic aortic
      valve area correlated better than peak and mean gradients with prosthetic size (r
      = 0.76, r = -0.45, and r = -0.39, respectively). On transthoracic study, 109
      patients (66%) showed minimal transprosthetic leakage. These normal values,
      obtained in a large number of patients with normofunctioning mitral and aortic
      Sorin Bicarbon valves, may help to identify Sorin Bicarbon prosthesis
      dysfunction.

PMID- 9282354
TI  - Atrial septal aneurysm: a new classification in two hundred five adults.
AB  - Atrial septal aneurysm is a localized "saccular" deformity, generally at the
      level of the fossa ovalis, which protrudes to the right or the left atrium or
      both. For 39 months we prospectively analyzed 205 consecutive patients in whom
      atrial septal aneurysm was diagnosed echocardiographically. The direction and
      movement of atrial septal aneurysms were carefully studied in multiple views,
      and, according to our findings, we now propose a new classification: type 1R if
      the bulging is in the right atrium only, type 2L if the bulging is in the left
      atrium only, type 3RL if the major excursion bulges to the right atrium and the
      lesser excursion bulges toward the left, type 4LR if the maximal excursion of the
      atrial septal aneurysm is toward the left atrium with a lesser excursion toward
      the right atrium, type 5 if the atrial septal aneurysm movement is bidirectional
      and equidistant to both atria during the cardiorespiratory cycle. We found an
      incidence of 1.9%, a mean age of 63 years (25 to 97 years), a female/male ratio
      of 2:1, valvular regurgitation 74%, hypertension 64%, left ventricular
      hypertrophy 38%, coronary heart disease 32%, patent foramen ovale 32%, pulmonary
      hypertension 31%, stroke 20%, dysrhythmias 16%, valvular prolapse 15%, and atrial
      septal defect 3%. No differences were found between mobile and motionless types
      of atrial septal aneurysm. However, differences were found between predominantly
      left bulging or right bulging atrial septal aneurysm (134 versus 57 patients), as
      well as other variables. All types of atrial septal aneurysm have particular
      clinical or echocardiographic characteristics. The new classification is a
      complete, simple, and practical form. Atrial septal aneurysm is associated with
      congenital and acquired heart diseases but also can present as an isolated
      abnormality.

PMID- 9282355
TI  - Echocardiographic patterns of myocardial fibrosis in hypertensive patients:
      endomyocardial biopsy versus ultrasonic tissue characterization.
AB  - Echocardiographic image texture has been demonstrated to reflect the physical
      properties of the tissue under examination. To evaluate the role of collagen in
      determining the echo pattern of the left ventricular wall, we studied nine
      hypertensive patients with left ventricular hypertrophy (left ventricular mass
      index > 125 gm/m2) and biopsy-proven different degrees of myocardial fibrosis by
      analyzing the echocardiographic examinations performed before the biopsy.
      Myocardial tissue was sampled under fluoroscopy and two-dimensional echo guidance
      in the interventricular septum. Collagen volume fraction (CVF; normal range up to
      2%) was taken as an index of fibrosis. The echo patterns were assessed by
      analyzing standard two-dimensional parasternal long-axis echocardiograms recorded
      on videotape. Images were color-coded at 256 levels (0 = yellow, 256 = black) and
      digitized off-line onto a personal computer. The region of analysis was set using
      a selection tool (20 x 10 mm) in the general area of septum where the specimen
      was taken. For each selection a color-level histogram, representing the frequency
      distribution, was derived with estimates of the average pixel intensity (mCS),
      skewness (SK), kurtosis (K), and the broad band (Bb) of the echoes about the
      distribution. Echo-derived parameters in each patient were compared with
      corresponding CVF values. CVF was out of range in all patients, ranging from 2.6%
      to 7.6% (mean 4.3% +/- 1.6%). No correlation was found between CVF and mCS,
      whereas a significant correlation was found at end diastole between CVF and the
      parameters describing histogram morphology, respectively, SK (r = 0.73), K (r =
      0.69), Bb (r = 0.72). These findings for the first time demonstrate in vivo in
      hypertensive patients with left ventricular hypertrophy an agreement between echo
      amplitude and histologically assessed collagen volume. Thus in our studied
      patients collagen content appears to be the major determinant of regional echo
      intensity, its increase resulting in a significant and progressive wider
      asymmetrical left shift (yellow) of the color histogram.

PMID- 9282356
TI  - Assessment of left ventricular wall motion abnormalities with the use of color
      kinesis: a valuable visual and training aid.
AB  - Accurate interpretation of left ventricular segmental wall motion by
      echocardiography is an important yet difficult skill to learn. Color-coded left
      ventricular wall motion (color kinesis) is a tool that potentially could aid in
      the interpretation and provide semiquantification. We studied the usefulness of
      color kinesis in 42 patients with a history of congestive cardiomyopathy who
      underwent two-dimensional echocardiograms and a color kinesis study. The expert's
      reading of the two-dimensional wall motion served as a reference for comparison
      of color kinesis studies interpreted by the expert and a cardiovascular trainee.
      Correlation between two-dimensional echocardiography and the expert's and
      trainee's color coded wall motion scores were r = 0.83 and r = 0.67,
      respectively. Reproducibility between reviewers and between operators was also
      assessed. Interobserver variability for color-coded wall motion showed a
      correlation of r = 0.78. Correlation between operators was also good; r = 0.84.
      Color kinesis is reliable and appears promising as an adjunct in the assessment
      of wall motion abnormalities by echocardiography. It is both a valuable visual
      aid, as well as a training aid for the cardiovascular trainee.

PMID- 9282357
TI  - Spontaneous echocardiographic contrast in the true lumen of a dissected aortic
      aneurysm.
AB  - Spontaneous echocardiographic contrast may be seen in the false and true lumens
      of dissecting aortic aneurysms. Using transesophageal echocardiography, we
      identified the false lumen as the source of spontaneous echocardiographic
      contrast in the true lumen of a patient with an aortic dissection.

PMID- 9282358
TI  - Transesophageal echocardiography in the presence of left atrial calcification.
AB  - Calcification of left atrial walls is a rare finding that has been reported to
      hamper visibility of intracardiac structures during transesophageal
      echocardiography because of the posterior location of the left atrium. We report
      a case of severe mitral stenosis associated with heavy left atrial calcification
      in which we could obtain good quality transesophageal imaging in spite of such a
      calcification. We conclude that calcification of left atrial walls does not
      necessarily imply a limitation of transesophageal echocardiography.

PMID- 9282359
TI  - Postinfarction atrioventricular septal rupture.
AB  - Postinfarction communication between a left ventricular aneurysm and the right
      atrium is a rare acquired disease. We report a case of a 72-year-old man who
      recently had dyspnea on minimal exertion and was found to have left ventricle-to
      right atrial shunt by two-dimensional transthoracic echocardiography. This
      diagnosis was confirmed with transesophageal echocardiography, cardiac
      catheterization, and angiography. The patient underwent successful repair but
      died of multisystem failure. This case shows the importance of transthoracic
      echocardiography for the adequate diagnosis and management of such cases.

PMID- 9282360
TI  - Detection of thrombotic cuspal obstruction of an aortic bioprosthesis with
      transesophageal echocardiography.
AB  - Bioprosthetic thrombotic obstruction is a rare complication which occurs
      relatively early after implantation. We present the transesophageal
      echocardiographic findings in a case of cuspal thrombosis of a Hancock aortic
      prosthesis which required valve replacement.

PMID- 9282361
TI  - [Gene mutation and pathology in human prion disease].

PMID- 9282362
TI  - [Prion disease in animals and experimental prion disease].

PMID- 9282364
TI  - [Clinical management of prion disease].

PMID- 9282363
TI  - [Clinical features of Creutzfeldt-Jakob disease and Gerstmann-Straussler
      syndrome].

PMID- 9282365
TI  - [Destructive spondyloarthropathy of the cervical spine in hemodialyzed patients].
AB  - To assess the prevalences and neurological symptoms of destructive
      spondyloarthropathy (DSA) and other cervical spinal diseases in long-term
      hemodialysis, a questionnaire survey of the medical histories and subjective
      sensory-motor symptoms was taken on 191 patients undergoing dialysis for 0.2-23
      years (mean 8.6 +/- 6.3) with a mean age of 56.6 +/- 11.8 years (range 23-86).
      Furthermore, plain radiographic examinations of the cervical spine were carried
      out in 90% of the patients, and neurologic examinations were also performed on 29
      patients. DSA was diagnosed in 18 cases (10%): moderate narrowing of the
      intervertebral space (NIS-I) in 8, severe narrowing (NIS-II) in 18, ossification
      of posterior longitudinal ligaments (OPLL) in 6, cervical spondylosis (CS) in 12
      and other abnormalities in 6; 104 cases were normal. NIS-I was considered to
      reflect an early stage of DSA. The age of patients with DSA (mean 61.5 +/- 10.2
      years), as well as with CS, was significantly higher than the normal group (52.2
      +/- 10.6; p < 0.001), but younger than CS (68.5 +/- 10.0). The duration of
      dialysis in DSA patients (mean 12.1 +/- 6.0 years) was the longest and
      significantly longer than normal (7.7 +/- 6.5; p < 0.01) and (:S patients (3.8 +/
      3.0; p < 0.001). Through comparative evaluations of prior histories of the
      diseases, such as diabetes mellitus, carpal tunnel syndrome, amyloid
      osteoarthropathy (AOA) and parathyroidectomy, along with large calcification of
      the nuchal soft tissues on plain films, it was found that DSA, in conjunction
      with NIS-I, correlated with only AOA (p < 0.05). Subjective sensory symptoms,
      which consisted chiefly of arthralgic type followed by polyneuritic type, were
      noted in 60% of all patients and 56% of DSA patients. No significant differences
      were evident between any two particular groups. The score of subjective motor
      symptoms of the lower extremities in 5 patients with myelopathy was significantly
      higher than that in 5 other patients without neurological disorders (p < 0.05).
      Thirty-eight percent of DSA patients showed myelopathy; the frequency was higher
      than those of previous similar studies (0 = 5%). In conclusion, this study
      demonstrated that 1) DSA occurred in 10% of dialysis patients, which was also
      evident in previous reports (9 = 10%); this prevalence was higher than those of
      CS or OPLL, 2) DSA correlated with the duration of dialysis and AOA, 3)
      subjective motor symptoms of the lower extremities could indicate presence of
      myelopathy whereas subjective sensory symptoms contributed little to differential
      diagnosis, and 4) a careful neurologic examination can more frequently disclose
      myelopathy in patients with DSA than so far believed.

PMID- 9282367
TI  - [Surgical management of intractable epilepsy in patients with ganglioglioma].
AB  - Long-standing intractable seizures are common manifestation of cerebral
      gangliogliomas. There is much controversy regarding the most appropriate surgical
      treatment (lesionectomy vs resection of the epileptogenic cortex with the lesion)
      for patients with intractable epilepsy associated with gangliogliomas. We
      reported 2 cases, in which the favorable seizure outcome was obtained following
      lesionectomy alone. (Case 1) Nine-year-old female developed attack of abnormal
      sensation in her left upper limb followed by motor seizure in her left limbs
      since 5 years old. MRI revealed hyperintense tumor in the right medial frontal
      lobe. Chronic invasive subdural recording showed that ictal onset zone was
      located in the hand motor area. Following lesionectomy alone, she became free
      from seizures. (Case 2) Eight-year-old girl had intractable generalized seizure
      since 6 years old. MRI revealed a cystic tumor in the right parietal lobe. She
      had multiple spike foci on electroencephalography and magnetoencephalography, and
      intraoperative electrocorticography failed to reveal the paroxysm. Following
      lesionectomy, she had good relief with less than one minor seizure per 1-3
      months. Thus, lesionectomy, even without resection of the epileptogenic cortex,
      may improve seizure outcome in patients with ganglioglioma-associated epilepsy.

PMID- 9282366
TI  - [Cooperative multicentre study on posttraumatic epilepsy].
AB  - A multicentre cooperative prospective study have been conducted to investigate
      the factors influencing posttraumatic epilepsy (PTE) and to evaluate the
      prophylactic effect of anticonvulsants. Since April 1994, patients with head
      injury have been observed following our protocol as follows; anticonvulsants are
      administered only to the patients with brain parenchymal injury for one month
      just after head trauma and no anticonvulsants are administered after one month
      after trauma to any patients except those with posttraumatic epilepsy (PTE).
      Brain parenchymal injury included traumatic subarachnoid hemorrhage, acute
      subdural hematoma, contusion, intracerebral hematoma, and diffuse axonal injury.
      To April 1996, 635 patients with head injury have been registered and analyzed.
      During the follow-up period, 14 patients (2.2%) developed PTEs, which had only
      been observed in patients with brain parenchymal injury. Multiple regression
      analysis revealed that two factors, early epilepsy and brain parenchymal injury,
      could contribute to the prediction of PTE. The frequency of PTE in this study was
      compared with that in our previous retrospective study (Nakamura, 1995), in which
      anticonvulsants were administered to the patients with head injury. There was no
      significant difference in the percentage of patients having PTE between the group
      treated without anticonvulsants in this study and the untreated group in previous
      retrospective study. Anticonvulsants treatment after head injury was not likely
      to have a prophylactic effect against the development of PTE.

PMID- 9282368
TI  - [Non-uremic neuropathy in hemodialysis patients].
AB  - We have reviewed 20 clinical records of hemodialysis patients with neuropathy
      admitted to the Department of Neurology during 1978 april through 1995 march. The
      clinical diagnosis was made based on clinical findings, neurophysiological
      examinations, and histopathological findings of sural nerve and peroneal muscle
      biopsies. Four out of twenty hemodialysis patients with neuropathy were non
      uremic neuropathy. The diagnosis of neuropathy of four patients were chronic
      inflammatory demyelinating polyneuropathy, neuropathy with graft versus host
      disease, Guillain-Barre syndrome, and subacute combined degeneration of the
      spinal cord. All patients improved after the treatment. It is important to
      consider the possibility of association of non-uremic neuropathy in hemodialysis
      patients.

PMID- 9282369
TI  - [Similarities in calcium and magnesium metabolism between amyotrophic lateral
      sclerosis and calcification of the spinal cord in the Kii Peninsula ALS focus].
AB  - Current epidemiological surveys in the Western Pacific area and Kii Peninsula
      have suggested that low calcium (Ca), magnesium (Mg) and high aluminum (Al) and
      manganese (Mn) in river, soil and drinking water may be implicated in the
      pathogenetic process of amyotrophic lateral sclerosis (ALS) and parkinsonism
      dementia (PD). The condition of unbalanced minerals was experimentally mimicked
      in this study using rats. Male Wistar rats, weighing 200 g, were maintained for
      90 days on the following diets: (A) standard diet, (B) low Ca diet, (C) low Ca-Mg
      diet, (D) low Ca-Mg diet with high Al. In the groups maintained on unbalanced
      mineral diets, calcium and magnesium contents of the bones were lower than those
      fed with standard diet. On the other hand, Ca content of CNS showed higher values
      in the unbalanced diet groups (especially in spinal cord of the low Ca-Mg plus
      high Al diet group) than those in the standard diet group. This was determined by
      neutron activation analysis (NAA) at Research Reactor Institute, Kyoto
      University. Also, Ca content in soft tissues of rats given unbalanced mineral
      diets was higher than those on standard diet. Mg content of soft tissues and
      spinal cord of rats was markedly lower in the low Ca-Mg plus high Al diet group
      than the other three groups as determined by inductively coupled plasma emission
      spectrometry (ICP). Six Kii cases with amyotrophic lateral sclerosis (ALS) also
      showed higher Ca and lower Mg contents in the CNS tissues than those of
      neurologically normal controls. As of today, calcification of the spinal
      ligaments (CSL) has been reported in only 120 cases in the world and 28 cases of
      CSL in the Kii Peninsula have been found in the same foci as ALS. We analyzed Mg
      content of 7 spinal bones and 10 ligaments of the CSL and Ca content of 5 spinal
      bones compared with controls. The CSL showed lower values of Mg contents in bones
      and ligaments compared to controls. The Ca content in bones of CSL was
      significantly lower than that of controls. These results suggest that the
      environmental factor may contribute to the pathogenesis of CSL due to low Ca and
      Mg intake as well as for ALS.

PMID- 9282370
TI  - [Acute necrotizing encephalopathy with horizontal gaze palsy].
AB  - Acute necrotizing encephalopathy (ANE) of childhood is a newly proposed disease
      entity characterized by symmetrically distributed necrotic brain lesions in the
      thalamus, cerebral white matter, brainstem, and cerebellum. We report a 4-year
      old girl with severe psychomotor delay and horizontal gaze palsy as sequelae of
      ANE at 17 months of age. The computed tomography showed bilaterally symmetrical
      low density areas in the thalamus and low density areas in the left middle
      cerebral artery (MCA) region and the posterior cerebral artery (PCA) region. MRI
      (T 1-weighted) revealed unevenly distributed small low signal intensity areas
      with scattered high intensity regions in the thalamus bilaterally. The T2
      weighted images showed multiple small low intensity areas around high intensity
      areas, and low signal intensity areas in the left middle cerebral artery (MCA)
      region and the posterior cerebral artery (PCA) region. In addition to severe
      psychomotor delay, the patient exhibited a peculiar eye movements. Horizontal
      ocular movement was impaired, but vertical ocular movement was almost completely
      normal. As clearly shown by MRI of the brain, the pontine tegmentum, including
      bilateral abducens nucleus, paramedian pontine reticular formation (PPRF), medial
      longitudinal fasciculus (MLF), and the facial nerve were affected, but the
      thalamo-mesencephalic junction, including the rostral interstitial medial
      longitudinal fasciculus (riMLF) and the nucleus of Cajal, was spared. To our
      knowledge, this is the first case of ANE associated with this selective ocular
      movement disorder ever reported. Because of the multiple symmetrical lesions and
      pons and the asymmetrical lesions of the MCA and PCA regions in the present case,
      occlusion of a single vessel could not account for the pathology. The
      pathophysiological mechanism of ANE is unknown. We postulate that some toxic or
      vasoactive agent caused vasospasm and subsequent breakdown of the blood-brain
      barrier, especially in the thalamus and pons, resulting in the unique
      distribution of the lesions and the rare eye movement disorder observed in the
      present case.

PMID- 9282372
TI  - [Mixed transcortical aphasia due to multiple deep white matter infarction in the
      dominant cerebral hemisphere: a case report].
AB  - We report a case of mixed transcortical aphasia (MTA) due to multiple cerebral
      infarction in the dominant hemisphere in an 80-year-old right-handed woman
      without hemiplegia. Her spontaneous speech was markedly reduced and auditory
      comprehension, reading and writing were severely disturbed. Although the
      repetition of sentences (at most 3 words) was relatively preserved, her speech
      was echolalic. Brain MRI showed bilateral multiple deep white matter infarction
      and subcortical infarction of the left parietal lobe, including left angular
      gyrus, but no abnormal signal intensities were detected in either Wernicke's or
      Broca's area. SPECT indicated a significant decrease in mean cerebral blood flow
      in both hemispheres, but there was no focal hypoperfusion in either speech area.
      We thought that the focal hypoperfusion observed in the right cerebellum
      indicated crossed cerebellar diaschisis. Electroencephalogram showed a diffuse
      reduction in the incidence of alpha waves in the left cerebral hemisphere. From
      these findings, we suggest that widespread hypofunction in the dominant
      hemisphere was important for the occurrence of MTA.

PMID- 9282371
TI  - [Autobiographical memory loss following herpes encephalitis].
AB  - We report a patient with prominent autobiographical memory (ABM) impairment, and
      discussed possible mechanisms of her deficits. The patient was a 36-year-old
      woman who suffered from herpes simplex encephalitis in November 1994. Four months
      after the onset, the neuropsychological examination disclosed that her
      intelligence, attention, language and frontal lobe functions were normal.
      Moderate anterograde amnesia was evident for visual materials, and she showed
      difficulties in retrieving visual images. Deficits in verbal learning were
      minimal. In contrast, her retrograde amnesia (RA) was severe. Further analyses
      clarified that memory for public events and personal semantic memory were
      relatively well preserved whereas ABM was severely impaired with no evidence of
      temporal gradient. Her performance on the ABM questionnaire was even worse than
      that of alcoholic Korsakoff patients. Interestingly, however, deficits in memory
      for public events also emerged when questions were presented with pictures
      instead of ordinary verbal questionnaires. The results suggest that her principle
      deficits consisted in utilizing visual information of the past events. Her access
      to and manipulation of the past visual representation/images were impaired.
      Consequently, her deficits were almost exclusive to ABM because visual
      information is most crucial for ABM. This material specific ABM impairment
      demonstrated in the present patient could be differentiated from nonspecific
      retrograde amnesia observed in typical focal RA patients. MRI, SPECT and PET
      demonstrated that the present patient had lesions basically in the right
      hemisphere, specifically in the medical temporal area including the hippocampus.

PMID- 9282373
TI  - [Oculomotor palsy].

PMID- 9282374
TI  - [A 76-year-old man with loss of vision and dementia].
AB  - We report a 76-year-old man who developed blurred vision and dementia. He was
      apparently well until April 4, 1990 (70-year-old at that time) when he had a
      sudden onset of bilateral loss of vision. Corrected vision was 0.1 (right) and
      0.09 (left). He was admitted to the ophthalmology service of our hospital on
      April 9, 1990, and neurological consultation was asked on April 11. Neurologic
      examination revealed alert and oriented man without dementia. Higher cerebral
      functions were intact. He had bilateral large visual field defects with loss of
      vision; he was only able to count the digit number with his right eye and to
      recognize hand movement with his left eye. Otherwise neurologic examination was
      unremarkable. General physical examination was also unremarkable; he had no
      hypertension. Cranial CT scan was normal on April 11; lumber spinal fluid
      contained 1 cell/microliter, 63 mg/dl of sugar, and 97 mg/dl of protein; myelin
      basic protein was detected, however, oligoclonal bands were absent. He was
      treated with methylprednisolone pulse therapy and oral steroid, however, no
      improvement was noted in his vision. He started to show gaze paresis to left,
      ideomotor apraxia, agnosia of the body, and dementia. Cranial CT scan on June 11
      revealed a low density area in the deep left parietal white matter facing the
      trigonal area of the lateral ventricle. He was discharged on July 2, 1990.
      Hasegawa dementia scale was 2/32.5 upon discharge. In the subsequent course, he
      showed improvement in his mental capacity and Hasegawa dementia scale was
      22.5/32.5 in 1991, however, no improvement was noted in his vision. In 1994, he
      started to show mental decline in that he became disoriented, and showed
      delusional ideation of self persecution and depersonalization with occasional
      confusional state. He also showed unsteady gait. Cranial MRI on February 13, 1996
      revealed a T2-high signal intensity lesion on each side of the parietal deep
      white matter more on the left and another T2-high signal intensity lesion in the
      left pons as well as in the right thalamus. He complained of right hypochondrial
      pain and was admitted to another hospital on April 22, 1996. He was markedly
      confused and demented. He continued to show bilateral loss of vision, but no
      motor palsy was noted. Cranial CT scan on April 23, 1996 revealed diffuse
      cortical atrophy and ventricular dilatation in addition to the low density areas
      in both parietal deep white matter. He developed jaundice in the middle of May.
      Abdominal CT scan revealed multiple low-to iso-density areas in the liver and
      marked iso-to high-density swelling of the right kidney. The patient expired on
      June 9th, 1996. The patient was discussed in a neurological CPC and the chief
      discussant arrived at the conclusion that the patient had had a carcinomatous
      limbic encephalitis with optic neuropathy and a choleduct carcinoma. Other
      opinions entertained included acute disseminated encephalomyelitis with optic
      neuritis, and granulomatous angiitis of the central nervous system. Some
      participants thought the primary site of the carcinoma was the right kidney with
      metastasis to the liver. Post mortem examination revealed a mixed type carcinoma
      in the right kidney with liver metastases. Neuropathologic examination revealed
      an incomplete softening in the optic chiasm and the left optic nerve, and in the
      left parieto-occipital areas. (The right hemisphere was frozen for future
      biochemical assay.) One of the adjacent cortical arteries had an organized
      thrombus. Other arteries and arterioles also showed sclerotic changes. Some of
      the leptomeningeal arteries were positive for Congored staining as well as for
      beta-amyloid immunostaining. Many senile plaques were seen diffusely in the
      cerebral cortex and neurofibrillary tangles were seen in the CA1 area and the
      parahippocampal gylus. No cellular infiltrations or demyelinated foci were seen.
      The neuropathologic features were consistent with circulatory disturbance based
      on the amyloid angiopa

PMID- 9282375
TI  - Nausea and vomiting, quality of life, and the oncology nurse.

PMID- 9282376
TI  - Physiologic mechanisms of nausea and vomiting in patients with cancer.
AB  - PURPOSE/OBJECTIVES: To review the current literature describing the multiple
      etiologies of nausea and vomiting in patients with cancer. DATA SOURCES: Reports
      of pertinent research, clinical articles, and book chapters. DATA SYNTHESIS: As a
      result of knowledge gained about the important role of serotonin in mediating the
      initial emetic response to antineoplastic drug administration, nurses have made
      tremendous strides in controlling acute chemotherapy-induced nausea and vomiting.
      The role of neurotransmitters other than serotonin in mediating the response of
      delayed or persistent nausea and vomiting remains unclear. Efforts continue to
      further describe the mechanisms and management of nausea and vomiting that occur
      as a result of other cancer-related conditions or treatments. CONCLUSIONS: A
      rational, often combinational approach to antiemetic therapy is derived from a
      working knowledge of the physiologic mechanisms associated with nausea and
      vomiting in patients with cancer. Assessment of the individual's precancer
      history and current physiologic and psychosocial status is the corner-stone of
      designing and providing effective therapies. IMPLICATIONS FOR NURSING PRACTICE:
      Understanding the physiologic mechanisms responsible for the cause and control of
      nausea and vomiting in patients with cancer facilitates creative use of drugs and
      nonpharmacologic strategies that are more likely to result in control of these
      distressing symptoms.

PMID- 9282377
TI  - Criteria for assessment of nausea, vomiting, and retching.
AB  - PURPOSE/OBJECTIVES: To promote accurate patient assessment, effective patient
      teaching, and useful research design and outcomes by defining the concepts of
      nausea, vomiting, and retching; to review the usefulness of self-care guides in
      assessing the patient's symptom experience. DATA SOURCES: Journal articles, the
      author's clinical experiences. DATA SYNTHESIS: The concepts of nausea, vomiting,
      and retching may be difficult for patients to describe and for nurses to assess.
      Measurement and assessment methods that accurately reflect the patient's
      experience are critical. CONCLUSION: Management of the individual symptoms of
      nausea, vomiting, and retching requires expert ongoing assessment of the
      patient's symptom experience that extends beyond the clinic or hospital visit.
      Information about symptom occurrence and distress and about self-care strategies
      used can play a crucial role in the identification, prevention, and management of
      symptom experience, with the good of improving the patient's quality of life.
      IMPLICATIONS FOR NURSING PRACTICE: Effective management of the patient's symptom
      experience depends on the oncology nurse's ability to differentiate occurrence
      and distress of the individual symptoms and to implement current knowledge not
      only of chemotherapy, antiemetic drugs, and nonpharmacologic interventions but of
      unerring ongoing assessments that lead to cost-effective, clinically useful
      patient outcomes. Basic scientific knowledge for research, practice, and
      education necessitates reliable, valid measurement tools that differentiate the
      components and dimensions of the individual symptoms.

PMID- 9282378
TI  - Risk factors and antiemetic management of chemotherapy-induced nausea and
      vomiting.
AB  - PURPOSE/OBJECTIVES: To review the emetic potential of chemotherapeutic agents and
      the specific factors that may help to identify patients who are most vulnerable
      to nausea and vomiting following chemotherapy. To review the classes of
      antiemetic drugs that effectively control nausea and vomiting associated with
      chemotherapeutic regimens. DATA SOURCES: Journal articles, abstracts, and
      clinical experience. DATA SYNTHESIS: The trend toward outpatient care requires
      aggressive antiemetic therapy from the outset, with clear recognition of the risk
      factors for chemotherapy-induced nausea and vomiting. The basic categories of
      antiemetics include 5-hydroxytryptamine, (5-HT3)-receptor antagonists,
      phenothiazines, butyrophenones, substituted benzamides, and cannabinoids.
      Additional agents often used in combination with these antiemetics include
      corticosteroids and benzodiazepines. CONCLUSIONS: The 5-HT3-receptor antagonists
      offer enhanced control of emesis while causing few side effects. For highly
      emetogenic chemotherapy regimens, the combination of 5-HT3-receptor antagonists
      and dexamethasone appears superior to other single agents or combinations in
      preventing nausea and vomiting. IMPLICATIONS FOR NURSING PRACTICE: Nursing care
      involves educating patients about self-care initiatives for effective management
      of chemotherapeutic side effects, including compliance with prescribed antiemetic
      regimens to prevent nausea and vomiting.

PMID- 9282380
TI  - Nonpharmacologic management of chemotherapy-induced nausea and vomiting.
AB  - PURPOSE/OBJECTIVES: To review the nonpharmacologic interventions indicated to
      prevent or control chemotherapy-induced nausea and vomiting. DATA SOURCES:
      Journal articles. DATA SYNTHESIS: Despite improvements in antiemetic drug
      therapy, as many as 60% of patients with cancer who are treated with
      antineoplastic agents experience nausea and vomiting. Anticipatory nausea and
      vomiting are thought to be caused by the behavioral process of classical
      conditioning. Most nonpharmacologic interventions that are used to prevent or
      control nausea and vomiting in patients with cancer are classified as behavioral
      interventions. Behavioral interventions involve the acquisition of adaptive
      behavioral skills to interrupt the conditioning cycle. CONCLUSIONS:
      Nonpharmacologic interventions appear to be effective in reducing anticipatory
      and post-treatment nausea and vomiting. IMPLICATIONS FOR NURSING PRACTICE: These
      behavioral interventions can be effective in reducing anticipatory and post
      treatment nausea and vomiting. Oncology nurses must learn these nonpharmacologic
      techniques and teach their patients to use them in combination with their
      prescribed antiemetic therapy.

PMID- 9282379
TI  - 5-HT3-receptor antagonists: a review of pharmacology and clinical efficacy.
AB  - PURPOSE/OBJECTIVES: To review the role of serotonin in chemotherapy-induced
      emesis and the mechanism by which 5-hydroxytryptamine3 (5-HT3)-receptor
      antagonists block the action of serotonin; to review the pharmacology and
      clinical efficacy of the 5-HT3-receptor antagonists in controlling nausea and
      vomiting induced by highly emetogenic chemotherapy regimens, including a
      comparison of agents in this class. DATA SOURCES: Journal articles and
      proceedings of clinical oncology conferences. DATA SYNTHESIS: Prior to the
      availability of 5-HT3-receptor antagonists, metoclopramide was the therapy of
      choice for prevention of cisplatin-associated emesis. Several randomized, double
      blind, comparative trials have established that a 5-HT3-receptor antagonist used
      alone is more effective than metoclopramide and equal to or better than the
      combination of metoclopramide and dexamethasone. CONCLUSION: 5-HT3-receptor
      antagonists contribute significantly to the current armamentarium of antiemetic
      agents. Clinical trials consistently have demonstrated a benefit with these
      agents that exceeds the previously established antiemetic standards. IMPLICATIONS
      FOR NURSING PRACTICE: 5-HT3-receptor antagonists have had a profound impact on
      the clinical management of acute chemotherapy-induced nausea and vomiting. Based
      on their unique mechanism of action and low toxicity profile, the 5-HT3-receptor
      antagonists offer a relatively new approach to controlling nausea and vomiting
      associated with highly emetogenic chemotherapy.

PMID- 9282381
TI  - Food safety: a commonly underestimated public health issue.

PMID- 9282382
TI  - Global estimation of foodborne diseases.
AB  - Foodborne diseases are one of the most widespread health problems, but because of
      weaknesses in foodborne disease surveillance and variation in reporting systems
      between countries, it is difficult to make an estimation of their true incidence.
      This paper describes the constraints in the collection of information on the
      incidence and/or prevalence of foodborne diseases, including investigation and
      reporting at national and international levels. It also makes an attempt to
      semiquantify the occurrence of foodborne diseases of microbial and parasitical
      origin in different regions of the world.

PMID- 9282383
TI  - Surveillance of foodborne diseases: what are the options?
AB  - Epidemiological data are needed for a variety of reasons, namely, informing
      public health authorities about the nature and magnitude of foodborne illnesses
      and their epidemiology, for the early detection of foodborne disease outbreaks,
      and for the planning, implementation and evaluation of food safety programmes.
      Thus, epidemiological surveillance of foodborne diseases is fundamental to any
      food safety programme. Various methods of foodborne surveillance may be utilized:
      (i) records for registration of deaths and hospital discharges; (ii) disease
      notification, (iii) sentinel surveillance, (iv) laboratory surveillance, (v)
      outbreak investigation and (vi) epidemiological research. This article reviews
      each method, its advantages and disadvantages, and its relevance for meeting the
      various objectives and needs.

PMID- 9282384
TI  - Epidemiology of foodborne diseases: tools and applications.
AB  - Food safety is a complex matter that depends on a number of interrelated
      environmental, cultural, and socioeconomic factors. The purpose of epidemiology
      and surveillance is to define these factors, how they interact, and their
      relative importance in foodborne infections. The tools epidemiologists use to
      study foodborne disease include surveillance of specific infections in humans,
      monitoring of contamination with specific pathogens in foods and animals,
      intensive outbreak investigations, collecting reports of outbreaks at the
      regional or national level, and studies of sporadic infections. With sufficiently
      elaborate systems of surveillance and investigation, it is possible to provide
      quantitative risk data for foodborne diseases that will permit the wisest
      allocation of food safety resources.

PMID- 9282385
TI  - Epidemiology of foodborne diseases: a worldwide review.
AB  - Acute foodborne disease infections and intoxications are much more of a concern
      to governments and the food industry today than a few decades ago. Some of the
      factors that have led to this include the identification of new agents that have
      caused life-threatening conditions; the finding that traditional agents are being
      associated with foods that were of no concern previously: an increasing number of
      large outbreaks being reported; the impact of foodborne disease on children, the
      aging population and the immunocompromised; migrant populations demanding their
      traditional foods in the countries of settlement; the ease of worldwide shipment
      of fresh and frozen food; and the development of new food industries, including
      aquaculture. However, to meaningfully monitor increases or decreases in foodborne
      disease requires an effective surveillance system at the local, national and
      international levels. To date, resources have been limited for most countries and
      regions to do this, and our current knowledge is based, for the most part, on
      passive reporting mechanisms. Laboratory isolation data and reports of notifiable
      diseases have some value in observing timely changes in case numbers of some
      enteric diseases, but they usually do not indicate the reasons for these trends.
      Special epidemiological studies are useful for the area covered, but it is often
      questionable whether they can be extrapolated to other areas or countries.
      Outbreak investigations tell us that a certain set of circumstances led to
      illness and that another outbreak may occur under similar but not necessarily
      identical conditions. Control programmes have often been triggered by the
      conclusions from investigations of specific outbreaks. Unfortunately, the agent/
      food combination leading to illness in many of the reported incidents were not
      predicted from existing databases, and no doubt foodborne agents will continue to
      surprise food control agencies in the foreseeable future. Nevertheless, data from
      around the world do show some common elements. Salmonella is still the most
      important agent causing acute foodborne disease, with Salmonella enteritidis and
      S. typhimurium being of most concern. Foods of animal origin, particularly, meat
      and eggs, were most often implicated. Desserts, ice cream and confectionery items
      were products also mentioned, but some of these would have egg as a raw or
      incompletely cooked ingredient. Incidents most frequently occurred in homes or
      restaurants, and the main factors contributing to outbreaks were poor temperature
      control in preparing, cooking and storing food. Clostridium botulinum, Salmonella
      and VTEC are more frequently documented in industrialized than in developing
      countries. ETEC, EPEC, Shigella, Vibrio cholerae and parasites are the main
      scourges in developing countries, but it is uncertain how many cases are
      attributed to food, to water or to person-to-person transmission. The apparent
      decrease of S. aureus and C. perfringens outbreaks in industrialized countries
      may be related to improved temperature control in the kitchen. An increasing
      number of illnesses are international in scope, with contamination in a
      commercial product occurring in one country and affecting persons in several
      other countries, or tourists being infected abroad and possibly transmitting the
      pathogen to others at home. For Salmonella, a rapid alert and response
      coordination is being encouraged through Salm-Net and other international
      programs. However, unless such a network is worldwide, tracking clusters of
      illnesses is going to fall on the countries where the first cases occur, and some
      of these have very limited resources for investigation and control. It was
      heartening to see funds recently being allocated to foodborne disease
      surveillance and control in several industrialized countries, but the same
      commitment is required by the World Health Organization for the international
      community.

PMID- 9282386
TI  - Chronic health effects of microbial foodborne disease.
AB  - The acute effects of foodborne disease are sometimes not the end of the illness.
      Several significant foodborne pathogens are capable of triggering chronic
      disease, and even permanent tissue or organ destruction, probably via immune
      mechanisms. Arthritis, septic and reactive, inflammatory bowel disease,
      haemolytic uraemic syndrome, Guillain-Barre syndrome, and possible several
      autoimmune disorders can be triggered by foodborne pathogens or their toxins.
      Research is needed to more fully understand the mechanisms by which the immune
      system is inappropriately activated by these common foodborne disease-causing
      agents.

PMID- 9282387
TI  - Economic costs and trade impacts of microbial foodborne illness.
AB  - This article presents the economic costs of foodborne diseases for selected
      countries, the approaches used to calculate these costs, and a discussion on the
      interaction between microbial food safety issues and international trade in food.
      The human illness costs due to foodborne pathogens are estimated most completely
      in the United States of America, where, each year, 7 foodborne pathogens
      (Campylobacter jejuni, Clostridium perfringens, Escherichia coli O157:H7.
      Listeria monocytogenes, Salmonella, Staphylococcus aureus, and Toxoplasma gondii)
      cause an estimated 3.3-12.3 million cases of foodborne illness and up to 3900
      deaths. These 7 pathogens are found in animal products and cost the United States
      an estimated $6.5-$34.9 billion (1995 US$) annually. The presence of foodborne
      pathogens in a country's food supply not only affects the health of the local
      population, but also represents a potential for spread to pathogens to visitors
      to the country and to consumers in countries which import food products. With
      more complete data on foodborne illnesses, deaths, costs and international trade
      rejections in each country, indicators could be developed by which changes in
      food safety can be monitored.

PMID- 9282388
TI  - Foodborne listeriosis.
AB  - Various epidemiological investigations of outbreaks and sporadic cases have
      clearly demonstrated that the consumption of contaminated food is responsible for
      a high proportion of listeriosis cases and Listeria monocytogenes has been
      increasingly recognized as an important foodborne pathogen over the last 15
      years. The emergence of listeriosis is the result of complex interactions of
      different factors: medical progress which increases the lifespan and allows
      immunodeficient people to survive, expansion of the food industry and cold
      storage systems as well as changes in food habits. None of these factors on its
      own is entirely responsible. Considerable research has attempted to characterize
      the organism, define the magnitude of the public health problem and its impact on
      the food industry, identify the risk factors associated with the disease, and
      devise appropriate control strategies. Nevertheless, a number of crucial
      questions remains incompletely elucidated (extent of the foodborne transmission
      of listeriosis, health status of apparently "healthy patients" with the possible
      role of an intercurrent infection or genetic susceptibility, how to distinguish
      highly virulent from less virulent strains of L. monocytogenes, factors
      contributing to the emergence of outbreaks, the possible role of healthy carriers
      in the epidemiology of listeriosis, etc.). To investigate the complexity of
      listeriosis requires the close collaboration of clinicians, epidemiologists,
      clinical and food microbiologists, food scientists and the food industry. A large
      amount of data has been accumulated during the past 10 years but more research is
      required to elucidate the epidemiology of the disease and the virulence of the
      causative agent.

PMID- 9282389
TI  - Enterohaemorrhagic Escherichia coli.
AB  - Enterohaemorrhagic Escherichia coli produces Verotoxins (Shiga-like toxins) and
      causes diarrhoea, haemorrhagic colitis and haemorrhagic uraemic syndrome. The
      mode of action of the Shiga toxin family has been well characterized in numerous
      studies which have demonstrated that the toxin has RNA N-glycosidase activity,
      which inhibits the binding of EF-1-dependent aminoacyl-tRNA to the 60S ribosomal
      subunit of eukaryotic cells, thus resulting in an inhibition of protein synthesis
      of the cells. In 1996, an unexpectedly large number of outbreaks of food
      poisoning due to E. coli O157:H7 occurred in Japan. In addition, many sporadic
      cases of E. coli O157:H7 were also reported and a total of about 8400 patients
      were recorded during that year. In most of these cases, the food vectors could
      not be identified. The possibility of developing a candidate vaccine is also
      discussed in this article.

PMID- 9282390
TI  - Foodborne salmonellosis.
AB  - Foodborne diseases caused by non-typhoid Salmonella are a very important public
      health problem and an economic burden in many parts of the world. Salmonellosis
      data from the WHO Global Databank on Foodborne Disease, from the literature and
      from the WHO Surveillance Programme in Europe were reviewed for the years 1985
      1995, showing an apparent increase in the incidence of salmonellosis in many
      parts of the world. In industrialized countries, this increase may be due to the
      emergence and increase of S. enteritidis and S. typhimurium DT104. In order to
      reduce the incidence of human foodborne salmonellosis, measures should be taken
      simultaneously during the production, processing, distribution, retail marketing
      and handling/preparation of food to prevent the introduction of Salmonella and
      its multiplication. These control measures need to be supported by effective
      foodborne disease surveillance programmes which make it possible to recognize and
      investigate outbreaks and emerging pathogens, and to assess the need for and
      evaluate interventions by monitoring longer term trends.

PMID- 9282391
TI  - Virus transmission via food.
AB  - Viruses are transmitted to humans via foods as a result of direct or indirect
      contamination of the foods with human faeces. Viruses transmitted by a faecal
      oral route are not strongly dependent on foods as vehicles of transmission, but
      viruses are important among agents of foodborne disease. Vehicles are most often
      molluscs from contaminated waters, but many other foods are contaminated directly
      by infected persons. The viruses most often foodborne are the hepatitis A virus
      and the Norwalk-like gastroenteritis viruses. Detection methods for these viruses
      in foods are very difficult and costly; the methods are not routine. Indicators
      that would rapidly and reliably suggest the presence of viral contamination of
      foods are still being sought. Contamination can be prevented by keeping faeces
      out of food or by treating vehicles such as water in order to inactivate virus
      that might be carried to food in this way. Virus cannot multiply in food, but can
      usually be inactivated by adequate heating. Other methods of inactivating viruses
      within a food are relatively unreliable, but viruses in water and on exposed
      surfaces can be inactivated with ultraviolet light or with strong oxidizing
      agents.

PMID- 9282392
TI  - Foodborne diseases in travellers.
AB  - It is encouraging that the problem of food- and waterborne disease in travellers
      is being increasingly recognized, but it is disappointing that to a large extent
      there is little effective action being taken. It is essential that the problem be
      recognized across government departments and joint programmes developed,
      particularly between ministries of health and tourism. Foodborne disease will
      always be a risk to travellers but this risk can be reduced by relatively simple
      programmes. The initial stage is to recognize the problem not just as an
      inconvenience to travellers but as an important economic factor which, unless
      controlled, can have severe effects on local, national and international trade.

PMID- 9282393
TI  - The role of food in the epidemiology of cholera.
AB  - Cholera is an acute dehydrating diarrhoeal disease, traditionally caused by
      vibrio cholerae O1, and also more recently by V. cholerae O139 (Bengal).
      Traditionally, water was recognized as the primary vehicle for transmission of
      cholera, but in the past 30 years, outbreaks of cholera associated with eating
      contaminated food have demonstrated that food also plays an important role,
      although in many instances water is the source of contamination of foods. Most
      commonly associated with cholera is seafood, both molluscan shellfish and
      crustaceans. Seafood may be contaminated in its natural environment or during
      preparation. Other food items associated with outbreaks are fruit and vegetables,
      meat, cooked grains, etc. Vegetables are usually contaminated by contact with
      sewage in soil and fruits when injected with contaminated water to increase
      weight and turgor. Food items initially free from V. cholerae organism may become
      contaminated when mixed with water, or other contaminated food, or through
      handling by infected persons who have not observed proper hygiene. Refrigeration,
      freezing, alkaline pH, high concentration of carbohydrate, humidity and absence
      of competing flora enhance the survival of V. cholerae in food. Survival of V.
      cholerae is shorter in food with acidic pH. Foodborne cholera can be averted by
      the hygienic preparation of food and its consumption. However, since the vehicles
      of transmission vary markedly from place to place, being affected by local
      customs and practices, selected control and preventive measures that are most
      important locally must be implemented. To this end, application of the Hazard
      Analysis and Critical Control Point system to food preparation is essential in
      order to identify the practices which may present a risk. Restrictions on
      importation of foods which do not present a risk of being contaminated from areas
      where cholera is endemic is not warranted.

PMID- 9282394
TI  - Establishment of microbiological safety criteria for foods in international
      trade. International Commission on Microbiological Specifications for Foods.
AB  - Microbiological safety is achieved by applying good hygienic practices throughout
      the food chain, "from farm to fork". Governmental food control is traditionally
      based on inspection of the facilities where foods are handled, and on testing
      food samples. Testing is usually applied to imported foods, when no information
      concerning the safety of a consignment is available. The microbiological safety
      is judged by means of microbiological criteria. Such criteria should, in the
      context of the WTO/SPS measures, be scientifically justified, and established
      according to the principles described by the Codex Alimentarius. However,
      microbiological testing is not a very reliable tool for consumer protection; the
      emphasis is currently shifting to the application of food safety management tools
      such as the Hazard Analysis Critical Control Point system (HACCP).

PMID- 9282395
TI  - Improving the safety of street-vended food.
AB  - An integrated plan of action for improving street food involving health and other
      regulatory authorities, vendors and consumers should address not only food
      safety, but also environmental health management, including consideration of
      inadequate sanitation and waste management, possible environmental pollution,
      congestion and disturbances to traffic. However, WHO cautions that, in view of
      their importance in the diets of urban populations, particularly the socially
      disadvantaged, every effort should be made to preserve the benefits provided by
      varied, inexpensive and often nutritious street food. Therefore, authorities
      concerned with street food management must balance efforts aimed at reducing the
      negative aspects on the environment with the benefits of street food and its
      important role in the community. Health authorities charged with responsibility
      for food safety control should match risk management action to the level of
      assessed risk. The rigorous application of codes and enforcement of regulations
      more suited to larger and permanent food service establishments is unlikely to be
      justifiable. Such rigorous application of codes and regulations may result in
      disappearance of the trade with consequent aggravation of hunger and
      malnutrition. Moreover, most codes and regulations have not been based on any
      systematic identification and assessment of health hazards associated with
      different types of foods and operations as embodied in the HACCP approach which
      has been recognized by Codex as the most cost-effective means for promoting food
      safety. WHO encourages the development of regulations that empower vendors to
      take greater responsibility for the preparation of safe food, and of codes of
      practice based on the HACCP system.

PMID- 9282396
TI  - Monitoring and assessment of dietary exposure to chemical contaminants.
AB  - The results of the Global Environment Monitoring System/Food Contamination
      Monitoring and Assessment Programme (GEMS/Food) and other monitoring programmes
      for priority contaminants in the diet, including lead, cadmium, mercury,
      polychlorinated biphenyls, organochlorine and organophosphorus pesticide residues
      and aflatoxin, are presented. These results are assessed with respect to
      established acceptable or tolerable intakes for these contaminants. While the
      assessments generally confirm the effectiveness of government efforts to prevent
      or reduce food contamination in industrialized countries, better exposure
      estimates for infants and children and other vulnerable groups should be
      calculated. In developing countries, little reliable information is available on
      the occurrence of food contamination. Without such information, the health of
      hundreds of millions of people may be threatened. For these countries, and
      especially those that employ older agricultural and industrial technologies,
      basic food contamination monitoring and assessment programmes should be
      established for at least those contaminants of priority concern. These programmes
      form an essential basis for developing effective intervention strategies and for
      efficient management of health and environment resources. In all countries,
      accidental and sporadic contamination is an ever present danger and continual
      vigilance is necessary to protect public health. All countries should identify
      institutions with the analytical capability to support epidemiological
      investigations of outbreaks of disease that may be associated with consumption of
      chemically contaminated food. All countries should participate in GEMS/Food to
      promote health-oriented, population-based monitoring at the national level.

PMID- 9282397
TI  - Modernizing food control systems: the experience of Thailand.
AB  - Food control is essential for the benefit of local consumers as well as
      international trade, which impacts on the overall social and economic concerns of
      the nation. Nevertheless, success in food control implementation will not be
      achieved by a single agency. Concerned agencies as well as food industries have
      to be fully aware of and be responsible for the production of good quality and
      safe foods. Efficient cooperation and coordination among the agencies concerned,
      therefore, is indispensable in the development of food safety. The Thai FDA has
      recently attempted to modernize its food control system by various approaches,
      including the establishment of a national food safety scheme and the introduction
      of modern technology as well as restructuring and changing the working system. It
      is anticipated that control along new directions may enhance better consumer
      protection in this country.

PMID- 9282398
TI  - [The 67th annual meeting of the Japanese Society for Hygiene. Tokyo, Japan. April
      2-5, 1997. Abstracts].

PMID- 9282399
TI  - [The 56th annual meeting of the Japan Radiological Society. Yokohama, Japan.
      April 4-6, 1997. Abstracts].

PMID- 9282400
TI  - Determination of iodine in milk and oyster tissue samples using combustion and
      peroxydisulfate oxidation.
AB  - Two methods are described for the preparation of samples for total iodine
      measurement in biological matrices. In the first method, the samples were
      combusted in a stream of oxygen to release iodine that, subsequently, was trapped
      in a solution as iodide. The second method is a new approach in which the samples
      were oxidized in a basic solution of peroxydisulfate. In this case, the iodine
      was retained in solution as iodate. Total iodine was measured by gas
      chromatographic analysis of the 2-iodopentan-3-one derivative. The methods were
      tested using Standard Reference Materials (SRMs) 1549 Non-Fat Milk Powder, and
      1566a and 1566 Oyster Tissue. Also, KI and KIO3 were used for testing the
      procedures. The results obtained for the SRMs, given as average +/- standard
      deviation in micrograms g-1, were: 3.39 +/- 0.14 and 3.40 +/- 0.23 for SRM 1549;
      4.60 +/- 0.42 and 4.51 +/- 0.45 for SRM 1566a; and 2.84 +/- 0.16 and 2.76 +/-
      0.06 for SRM 1566; values corresponding to combustion and wet oxidation,
      respectively. Overall, the absolute recoveries varied between 91 and 103%. These
      methods can also be used in the preparation of targets for the measurement of
      129I using accelerator mass spectrometry.

PMID- 9282401
TI  - Slurry sampling for hydride generation atomic absorption spectrometric
      determination of arsenic in cigarette tobaccos.
AB  - The development of a slurry sampling hydride generation atomic absorption
      spectrometric (HGAAS) method for the determination of arsenic in cigarette
      tobacco samples is described. The method is relatively simple and has been shown
      to give values of total arsenic close to those obtained using methods requiring
      total dissolution and decomposition of all vegetable matter before analysis. Pre
      treatment of samples slurried in nitric acid by ultrasonication permitted the
      extraction of about 90% of the total arsenic from tobacco samples. Further
      improvement in the recovery efficiency (up to 93-94%) was accomplished by the use
      of an additional step of short microwave-accelerated treatment. L-Cysteine was
      used as a pre-reduction agent. The accuracy and precision of the slurry sampling
      HGAAS method were studied using the certified reference material (CRM) CTA-OTL-1
      Oriental Tobacco Leaves. Under the optimum conditions, as little as 2.6 ng of
      arsenic can be detected. The relative standard deviation of the overall procedure
      was calculated to be below 7.6% at arsenic concentration levels of 0.5-0.9 mg kg
      1 and the analytical results obtained for the CRM agreed with the certified
      value. The main factors that influenced the reliability of the method were sample
      homogeneity, particle size and slurry concentration.

PMID- 9282402
TI  - Phosphorimetric determination of indomethacin in pharmaceutical formulations.
AB  - A simple, rapid and sensitive method for the determination of indomethacin was
      developed based on solid-surface room-temperature phosphorimetry. Phosphorescence
      emission was induced by the indomethacin hydrolysis reaction in a basic medium.
      Chromatography paper treated for background reduction was employed as a solid
      substrate. The use of four heavy-atom salts and sodium dodecyl sulfate was
      optimized to estimate an absolute limit of detection at the subnanogram level. A
      calibration curve with a linear dynamic range extending over two orders of
      magnitude (3.0 x 10(-7)-1.0 x 10(-4) mol dm-3) was obtained. The recovery of the
      method (98.4 +/- 6.8%) was tested using commercial formulations containing
      indomethacin as the only anti-inflammatory agent.

PMID- 9282403
TI  - Quantitative studies of aluminium binding species in human uremic serum by fast
      protein liquid chromatography coupled with electrothermal atomic absorption
      spectrometry.
AB  - Fast protein liquid chromatography (FPLC) was used with electrothermal atomic
      absorption spectrometric (ETAAS) detection for quantitative studies of aluminium
      binding species in unspiked human uremic serum. A rapid and reproducible
      separation of human serum proteins and other aluminium binders (citrate and
      desferroxiamine) was achieved on a Mono Q (HR 5/5) anion-exchange column using a
      sodium chloride gradient (0-0.25 mol l-1) at the physiological human serum pH of
      7.4 (0.05 mol l-1 buffer TRIS-HCl). The aluminium distribution in the column
      fractions was determined by ETAAS. Aluminium contamination was avoided by using
      an inert chromatographic system equipped with an on-line aluminium-chelating
      scavenger column (Kelex 100-impregnated silica C18). The sensitivity of the
      proposed method (detection limit for Al in serum = 5 micrograms l-1) allowed
      aluminium speciation studies at clinically relevant concentrations (unspiked
      serum from dialysis patients). The results obtained confirmed that transferrin is
      the only serum protein binding aluminium and it contains about 90% of total serum
      aluminium (post-elution aluminium recovery = 105 +/- 5%). It was also confirmed
      that in the presence of the chelating drug desferrioxamine (DFO) most of the
      serum aluminium (80%) is bound to DFO.

PMID- 9282405
TI  - Determination of aflatoxin B1-DNA adduct in rat liver by enzyme immunoassay.
AB  - A simple, rapid and highly sensitive indirect competitive enzyme-linked
      immunosorbent assay (ELISA) to determine aflatoxin B1 (AFB1)-DNA adducts is
      reported. Polyclonal antibodies specific to the aflatoxin B1-N7-guanine adduct
      were produced using a novel synthetic antigen, bovine serum albumin (BSA)-guanine
      AFB1. The antibodies were characterized by the Ouchterlony double diffusion
      technique and by antibody capture assay. The working range of the indirect
      competitive assay developed was between 0.45 and 330 ng of the analyte [calf
      thymus (CT)-DNA-AFB1]. A 50% inhibition was attained at 15 ng of the analyte (CT
      DNA-AFB1). The antibody capture assay indicated that the antibody produced cross
      reacted 100, 92 and 110% with BSA-guanine-AFB1, CT-DNA-AFB1 and CT-DNA
      formamidopyrimidine-AFB1, respectively. When free AFB1 and guanine were used as
      competing analytes, the antibodies showed < or = 5% and zero cross-reactivity at
      the 50% inhibition level. Spiking studies indicated a recovery in the range 96-97
      and 74-78% when standard CT-DNA-AFB1 was added to 10 mM phosphate buffer (pH 7.2)
      and control rat liver tissue, respectively. Rats exposed to a single oral dose of
      1 mg kg-1 body mass of pure AFB1 were used to validate the method. The AFB1-DNA
      adduct formed in the liver tissue after 48 h of exposure was determined using the
      ELISA method developed. The liver AFB1-DNA adduct ranged between 6.06 and 7.94
      micrograms mg-1 DNA. The proposed method may find application in the biological
      monitoring of aflatoxin B1 in molecular epidemiological studies to assess the
      dietary exposure of aflatoxins.

PMID- 9282404
TI  - Evaluation of tryptamine in an impinger and on XAD-2 for the determination of
      hexamethylene-based isocyanates in spray-painting operations.
AB  - Tryptamine was evaluated as a reagent for derivatizing hexamethylene diisocyanate
      (HDI) monomer and oligomers during actual spray-painting operations. In one side
      by-side sampling study, an impinger filled with 1-(2-methoxyphenyl)piperazine in
      toluene was compared with a second impinger filled with tryptamine in dimethyl
      sulfoxide (DMSO). The amount of HDI monomer obtained was below the limit of
      quantification for both impingers. The amount of HDI oligomer obtained when using
      1-(2-methoxyphenyl)piperazine in toluene was comparable to the amount obtained
      when using an impinger filled with tryptamine in DMSO. In a second side-by-side
      sampling study, a tryptamine-coated XAD-2 resin was used as a sorbent. The
      relative collection efficiency of the tryptamine-coated XAD-2 resin was on
      average 60% of the value obtained using an impinger filled with tryptamine in
      DMSO. The results indicate that using an impinger filled with tryptamine in DMSO
      gives higher concentrations of isocyanate than a tryptamine-coated XAD-2 sorbent
      for HDI monomer and oligomer.

PMID- 9282406
TI  - The concept of uncertainty as applied to chemical measurements.
AB  - The calculation of uncertainty as recommended for physical measurements cannot be
      transferred readily to chemical measurements. Physical measurements and chemical
      measurements have entirely different error patterns that behave differently on
      replication. Correctable local bias predominates in physical systems and random
      error is minor; random error predominates in chemical systems and bias is
      difficult to identify and eradicate. Therefore bias must be monitored by
      randomizing in the interlaboratory environment, a concept not handled by the
      conventional ISO treatment of uncertainty.

PMID- 9282408
TI  - Controlled-release budesonide in Crohn's disease.
AB  - Budesonide is a glucocorticoid with high local activity but much lower systemic
      availability than prednisolone. Topical formulations have long been licensed for
      use in asthma and rhinitis. Here we discuss a new orally active controlled
      release preparation of budesonide (Entocort CR-Astra) formulated specifically for
      treating patients with Crohn's disease affecting the ileum and/or ascending
      colon. The manufacturer claims that the preparation "targets the ileum and
      ileocaecal area, achieving rapid results equivalent to prednisolone" with a "low
      level of systemic steroid side effects".

PMID- 9282407
TI  - Major advances in the treatment of HIV-1 infection.
AB  - Eight drugs are now marketed in the UK for the treatment of human
      immunodeficiency virus (HIV) infection. Here we discuss these drugs and review
      the evidence that they delay HIV disease progression and prolong survival.

PMID- 9282409
TI  - Using beta 2-stimulants in asthma.
AB  - Beta 2-selective adrenoceptor agonists (beta 2-stimulants) have been used for 30
      years for the relief of symptoms in patients with all grades of asthma. They can
      also be used before activities likely to precipitate airway narrowing and are
      sometimes taken as regular treatment by patients with chronic asthma. The first
      beta 2-stimulants to be introduced were shorter-acting drugs such as salbutamol
      and terbutaline. The longer-acting beta 2-stimulants, salmeterol and eformoterol
      were developed more recently and their role in treating asthma is not yet fully
      defined. In this article we review the current place of beta 2-stimulants in
      asthma management.

PMID- 9282410
TI  - The management of primary open angle glaucoma.
AB  - Glaucoma is one of the commonest causes of blindness in the world. In the UK,
      about 7% of people over the age of 75 years have primary open angle glaucoma, the
      most common type of glaucoma and the cause of visual impairment in about 13% of
      those registered blind. Early detection and treatment can usually prevent
      blindness. However, half of all patients with primary open angle glaucoma in the
      UK do not present until vision has begun to deteriorate. Here we consider ways of
      improving detection and management.

PMID- 9282411
TI  - Which prophylactic aspirin?
AB  - Low doses of aspirin are now a standard part of the management of patients with
      thromboembolic disease. One risk of taking even low doses is bleeding from the
      gut, and various aspirin formulations are marketed with claims that they reduce
      this problem. In this article we review the formulations available and consider
      their relative safety.

PMID- 9282412
TI  - Generic medicines--can quality be assured?
AB  - Generic prescribing is steadily increasing, a change which we and others
      encourage. The proportion of prescriptions written in general practice in England
      using the generic (approved) name increased from 35% in 1985 to 55% in 1995.
      Where a product is prescribed generically, the alternatives that could be
      supplied should be equivalent, to ensure that patients are not put at risk. In
      this article, were view how the equivalence and quality of generic drugs are
      assured and consider whether the process is adequate.

PMID- 9282413
TI  - Riluzole for amyotrophic lateral sclerosis.
AB  - Around one in 20,000 adults in the UK will develop amyotrophic lateral sclerosis,
      the commonest variant of motor neurone disease. Riluzole (Rilutek-Rhone-Poulenc
      Rorer) was launched in the UK in August 1996 as "the first anti-excitotoxic agent
      proven to extend life in amyotrophic lateral sclerosis". We review the clinical
      data on the effectiveness of riluzole and assess its place in the management of
      amyotrophic lateral sclerosis, a condition that is invariably fatal and has a
      median survival time from symptom onset of about 2.5 years.

PMID- 9282414
TI  - Late complications of radiotherapy.
AB  - Radiotherapy is a standard part of cancer management. Irradiation often causes
      acute unwanted reactions, such as nausea, diarrhoea or redness of the skin,
      which, although troublesome, normally resolve within a few weeks. Acute bone
      marrow depression can also occur, particularly following irradiation of the whole
      body, but this too may be transient. In some patients, unwanted reactions develop
      months or years after treatment is completed. Here we review these late
      complications and consider how they can be prevented or managed.

PMID- 9282415
TI  - Managing post-term pregnancy.
AB  - The optimal management of post-term pregnancy (gestation lasting 42 weeks or
      more) is not resolved. The risk to the fetus increases as pregnancy continues
      post term and this has to be balanced against the risks associated with
      induction. Here we consider whether routine induction at around 42 weeks has any
      advantages over expectant management, in which pregnancy is allowed to run its
      natural course unless the fetus (or mother) develops features of distress.

PMID- 9282416
TI  - Helping patients who misuse drugs.
AB  - The number of people with problems related to drug misuse has risen since we last
      discussed this topic 12 years ago. New drugs such as 'crack' (the smokeable form
      of cocaine) and ecstasy have appeared, while the abuse of diamorphine (heroin),
      amphetamines and benzodiazepines has become more widespread. By sharing needles
      and syringes, those injecting drugs are at risk of infection with hepatitis B,
      hepatitis C and the human immunodeficiency virus (HIV). Here we discuss the drugs
      that are commonly misused and the priorities in management. We consider the
      potential role of GPs and the primary care team in that management.

PMID- 9282417
TI  - Helicobacter pylori testing kits.
AB  - Eradication of Helicobacter pylori helps prevent ulcer recurrence in patients
      with duodenal or gastric ulcers but its value is less clear in those with other
      causes of dyspepsia. A quick and reliable test for diagnosing infection should
      simplify management. Several testing kits are now being used and in this article
      we assess their validity.

PMID- 9282418
TI  - Moxonidine for hypertension.
AB  - Moxonidine (Physiotens-Solvay) was introduced last year as the first of a new
      class of centrally-acting antihypertensive agents, the selective imidazoline
      receptor agonists. The manufacturer claims that moxonidine "accurately targets
      imidazoline receptors at the cardiovascular control centre in the brainstem" and
      is "as effective as current first-line therapies for essential hypertension".
      Other claims suggest that it causes fewer unwanted effects than older centrally
      acting antihypertensive drugs such as clonidine and methyldopa. Is moxonidine a
      useful addition to the growing number of antihypertensives on the market?

PMID- 9282419
TI  - Aminoglycosides once daily?
AB  - Six aminoglycosides (amikacin, gentamicin, kanamycin, netilmicin, streptomycin
      and tobramycin) are licensed for parenteral use in the UK. As a group, they
      remain effective against infections caused by aerobic gram-negative organisms and
      Staphylococcus aureus, including species commonly resistant to beta-lactam
      antibiotics. However, their use is limited by the severity of their unwanted
      effects and by their route and frequency of administration; traditionally, they
      have been given intravenously two to four times daily. Increasingly, they are
      being given once daily in an attempt to simplify treatment without reducing
      efficacy or increasing toxicity. Here we evaluate the advantages and
      disadvantages of this once-daily approach.

PMID- 9282420
TI  - Mycophenolate mofetil for the transplanted kidney?
AB  - Mycophenolate mofetil (CellCept-Roche) is a new immunosuppressant indicated "in
      combination with cyclosporin and corticosteroids for the prophylaxis of acute
      transplant rejection in patients receiving allogeneic renal transplants". Here we
      review mycophenolate mofetil and assess whether it offers any additional benefits
      to conventional therapy.

PMID- 9282421
TI  - Managing self-harm: the legal issues.
AB  - Each year about 100,000 people present to UK hospitals with deliberate self-harm,
      the most common form of which is poisoning with medicines or other
      pharmacologically active substances. As may as 95% of self-poisonings are
      intentional drug overdoses but only around 40% of patients who poison themselves
      express a wish to die. In many instances, the final outcome is determined by the
      speed with which treatment is started. Here we concentrate on the legal issues
      facing doctors when patient declines treatment.

PMID- 9282422
TI  - Paclitaxel and docetaxel in breast and ovarian cancer.
AB  - Three years ago we reviewed paclitaxel (Taxol-Bristol-Myers Squibb), the first
      taxoid cytotoxic drug to be marketed. At that time it was licensed for the
      treatment of women with metastatic ovarian cancer resistant to standard platinum
      containing therapy; we concluded that any benefits of paclitaxel were unproven.
      Since then the licence has been extended to include first-line treatment (in
      combination with cisplatin) of advanced ovarian cancer and treatment of
      metastatic carcinoma of the breast in patients who have failed, or are not
      candidates for, standard anthracycline-containing therapy. A second taxoid,
      docetaxel (Taxotere-Rhone-Poulenc Rorer) was launched in 1996. It is licensed for
      the treatment of patients with breast cancer that is locally advanced or
      metastatic, and which is either resistant to, or has recurred after, cytotoxic
      therapy, or has relapsed during adjuvant cytotoxic therapy. In each case, the
      previous cytotoxic therapy should have included an anthracycline drug (such as
      doxorubicin). Here we review the place of the two taxoids in the treatment of
      ovarian and breast cancer.

PMID- 9282423
TI  - Key dilemmas in prescribing and the provision of health.
AB  - Decision-making in health provision is rarely straightforward. Choices are
      probably easiest when trial data are clear and the consequences essentially
      trivial. As information becomes more speculative, outcomes more critical and the
      environment more hostile, dilemmas arise. These and related issues were addressed
      in the fifth annual Drug and Therapeutics Bulletin symposium 'Key Dilemmas in
      Prescribing and the Provision of Health,' which was held in March. Here we
      summarise the key views raised in the talks and subsequent discussion.

PMID- 9282424
TI  - Drug-induced agranulocytosis.
AB  - Drug-induced agranulocytosis is a rare, potentially fatal idiosyncratic reaction
      that can occur unpredictably with a wide variety of drugs when taken in a
      conventional dose. In this article, we discuss its diagnosis and management and
      we consider the drugs most commonly involved and ways of minimising risk. We do
      not consider the dose-related granulocytopenia that commonly complicates
      treatment with cytotoxic and other myelosuppressant drugs, nor the rarer
      reaction, aplastic anaemia.

PMID- 9282425
TI  - Peak flow meters and spirometers in general practice.
AB  - Since peak flow meters were first made available on FP10 prescription in 1990,
      they have become widely used in general practice for the diagnosis and monitoring
      of asthma. Patients can also use them at home as part of a self-management plan.
      Now there is increasing interest in the use of spirometers in general practice
      for diagnosing chronic obstructive pulmonary disease and monitoring patients'
      progress. We consider how peak flow monitoring and spirometry can be used to
      greatest advantage in general practice.

PMID- 9282426
TI  - New aromatase inhibitors for breast cancer.
AB  - Anastrozole (Arimidex-Zeneca) and letrozole (Femara-Novartis) are the first
      selective, oral, non-steroidal aromatase inhibitors. They are licensed for the
      treatment of advanced breast cancer in postmenopausal women where tamoxifen or
      other anti-oestrogen therapy has failed. The manufacturers of both drugs claim
      that their products are more effective, less toxic and better tolerated than the
      progestogen megestrol acetate, the standard therapy in this clinical situation.
      We assess these claims.

PMID- 9282427
TI  - A notable anniversary in the history of medical illustration.
AB  - The author argues that medical illustration is not a cross-cultural phenomenon
      known since ancient times, but a modern tradition born out of the intellectual
      climate of 18th century Europe. In this climate, photography was always desirable
      in theory, and medical illustrators grasped photographic technology as soon as it
      became available in the 1840s, quickly adapting it to their own purposes. The
      earliest surviving clinical photograph can be identified as that of a woman with
      a goitre taken by Hill and Adamson ca. 1847, in which case medical photography
      has this year reached its 150th anniversary. The author also offers a revised
      account of the speed and enthusiasm with which early medical illustrators
      recognized the opportunities afforded by new forms of technology.

PMID- 9282428
TI  - A new screening tool for diabetic retinopathy: the Canon CR5 45NM retinal camera
      with Frost Medical Software RIS-lite digital imaging system.
AB  - The introduction of the Canon CR5 45NM non-mydriatic retinal camera with the
      Frost Medical Software RIS-Lite digital imaging system provides a new screening
      tool for diabetic retinopathy with potential for remote diagnosis and
      telemedicine. This paper presents a description and early evaluation of the
      system.

PMID- 9282429
TI  - Copyright protection of images in the digital environment.
AB  - All creators of copyright-protected works are re-assessing the protection and
      exploitation of their works in the digital environment. This article attempts to
      define 'digital' in a copyright context. It reminds artists and photographers of
      the essentials of copyright as they already apply in the UK before it looks at
      how those essentials may apply to images circulating in the digital environment.
      Finally it covers some of the key issues which artists and other creators are now
      having to address in their day to day work.

PMID- 9282430
TI  - Photography of operative techniques and pathology during arthroscopy using a
      second arthroscope.
AB  - The use of two arthroscopes is recommended to reduce the time needed for
      photography eliminating the need to remove video control from the main
      arthroscope, to record pathology and operative techniques for teaching without an
      additional light source.

PMID- 9282431
TI  - Should clinical lecturers produce their own CAL material?
AB  - Clinical lecturers may embark upon the task of creating CAL material unaware of
      the effort required to produce the simplest of programs. This study aimed to
      measure the effort involved in such a task in order that those contemplating such
      development might make a judgement which is well informed. The study entailed a
      computer literate, yet non-programming clinical lecturer producing a ten-minute
      CAL program using three different authoring templates. A diary and time log were
      kept. The resulting pleces of software are discussed as well as the process by
      which they were created.

PMID- 9282432
TI  - Through the keyhole.

PMID- 9282433
TI  - Recertification--time to bite the bullet.

PMID- 9282434
TI  - Aeromedical evacuation in Bosnia.
AB  - The objective of this study was to assess the value of aeromedical evacuation
      when compared to road ambulance transportation in predominantly trauma patients
      in a rural area. Uniquely, trauma was the most common presenting condition (75%),
      distances to secondary care facilities were long and road routes were poor with a
      risk of being mined. Data were collected of all British aeromedical flights in
      Multi-National Division Southwest, Bosnia-Herzegovina, over a six-month period,
      and benefit to the patient was assessed by a panel of experts when compared to
      calculated road ambulance evacuation. Sixty-nine patients were evacuated by air
      on 57 flights and transported to a secondary care facility for further
      management. The panel of experts found that only 15 of the 69 patients (22%) had
      benefited from aeromedical evacuation. This study again shows the low benefit to
      the patient from indiscriminate use of aeromedical evacuation, despite the air
      ambulance being operated in apparently ideal conditions of a high percentage of
      trauma, a rural setting and poor road communications. Crew safety and the high
      costs further highlight the need to devise a system that can screen out
      unnecessary flights and identify those patients who would benefit most.

PMID- 9282435
TI  - The Sir James Watt Hyperbaric Medicine Unit--an asset to the Royal Hospital
      Haslar and the defence medical services.

PMID- 9282436
TI  - Telemedicine--'toys for the boys' or an essential tool?

PMID- 9282437
TI  - The mortality of Royal Naval submariners 1960-1989.
AB  - The mortality pattern of 15,318 Royal Naval submariners has been examined to
      asses the long term effects on health of serving in submarines. The main outcome
      measures used were standardised mortality ratios (SMRs) which present the
      submariners' mortality rates as a percentage of those for men in England and
      Wales. The SMR for all causes of death combined was low at 86, this being
      comparable to findings in other studies of Armed Forces personnel. Cancer
      mortality was particularly low with an SMR of 69 and there was no particular
      cancer site which showed an excess. Raised mortality from digestive diseases was
      seen: the excess was attributable to cirrhosis of the liver which gave rise to an
      SMR of 221 based on 12 deaths, alcohol being a contributory factor in eight. This
      excess mortality from cirrhosis was concentrated in the period 1970-79 and
      occurred in men who had left the Royal Navy. Deaths from accidents and violence
      were also higher than expected with an SMR of 115, but this was due to high
      levels of accidents occurring after discharge from the Navy.

PMID- 9282438
TI  - Prevention of heat strain by immersing the hands and forearms in water.
AB  - The effectiveness of hand immersion in water at 10 degrees C, 20 degrees C and 30
      degrees C as a technique for reducing heat strain in Royal Navy (RN) personnel
      has been investigated at the Institute of Naval Medicine (INM). Four subjects
      exercised at a moderate work rate, whilst wearing fire fighting clothing in an
      environmental chamber at 40 degrees C. The subjects reached heat strain safety
      limits within 45 minutes of commencing work at which point they rested in the
      heat for 30 minutes whilst they underwent one of four experimental conditions:
      without intervention (control); or with their hands immersed in water at 10
      degrees C, 20 degrees C or 30 degrees C. The experiment was repeated on a further
      three days so that the subjects undertook each experimental condition in a
      balanced randomised order. During the control condition without hand immersion
      the subjects were unable to cool. Immersion of the hands in water (at 10 degrees
      C, 20 degrees C or 30 degrees C) significantly (P < 0.05) lowered body core
      (auditory canal) temperature within ten minutes. Assessing the effectiveness of
      this technique by the initial rates of core temperature reduction, revealed that
      immersion of the hands was more effective the colder the water. Following 20
      minutes of hand immersion mean core temperature had dropped from 38.5C to:
      36.9(standard deviation 0.19) degrees C, 37.3(0.18) degrees C, and 37.8(0.10)
      degrees C, in 10 degrees C, 20 degrees C and 30 degrees C water respectively.
      Cooling powers estimated from changes in mean body temperature were 334, 307 and
      113 watts using 10 degrees C, 20 degrees C and 30 degrees C water respectively.
      These results indicate that hand immersion in water at a temperature of between
      10 degrees C and 30 degrees C is an efficient means of cooling heat stressed
      personnel who have been exercising. This simple and effective technique may be
      applied to many industrial and military tasks to reduce heat strain, lower the
      risk of heat injury, and increase safe total work times in the heat. For the RN,
      hand immersion could be used in fire fighting, damage control and NBC operations
      where personnel alternately work and rest.

PMID- 9282439
TI  - Emesis research: a concise history of the critical concepts and experiments.

PMID- 9282440
TI  - Singular experiences--the early history of anaesthesia in the Royal Navy 1847 to
      1854.

PMID- 9282441
TI  - [Gaucher's disease in pregnancy].
AB  - A case of Gaucher's disease associated with pregnancy is reported. Although
      clinical symptoms were not present, portal hypertension was detected by
      ultrasound in the 13th week of pregnancy. Maternal anemia implied the use of
      erythropoietin from the 33rd week onwards. Good perinatal and maternal outcomes
      were achieved and there were no hemorrhagic complications.

PMID- 9282442
TI  - [Scoliosis of sudden evolution due to lumbar osteoblastoma].
AB  - The clinical presentation and treatment of a case of osteoblastoma of the lumbar
      spine (L4) is described, with a notable delay between the onset of symptoms and
      the definitive diagnosis (2 years). Besides scoliosis, the usual roentgenograms,
      bone scans, CAT and MRI, did not show any relevant abnormality, which is a
      possibility that does not allow us to exclude the diagnosis of this tumor in a
      young patient with lower back pain and a rigid scoliosis.

PMID- 9282443
TI  - Evidence-based dentistry.

PMID- 9282445
TI  - New impression technique.

PMID- 9282446
TI  - Evidence-based dentistry.

PMID- 9282444
TI  - Evidence-based dentistry.

PMID- 9282447
TI  - An unusual radiographic finding.

PMID- 9282448
TI  - Treating oral candidiasis: potentially fatal.

PMID- 9282449
TI  - Effectiveness of periodontal treatments on cyclosporine-induced gingival
      overgrowth in transplant patients.
AB  - OBJECTIVE: Evaluation of the effectiveness of periodontal treatments on
      cyclosporine-induced gingival overgrowth. DESIGN: Longitudinal study between
      months 6 and 12 after transplant, in 80 cyclosporine-treated heart, liver and
      kidney transplant patients. SETTING: Madrid Puerta de Hierro Hospital. SUBJECTS
      AND METHODS: The 37 patients who had developed overgrowth in the sixth month were
      randomly split into three study groups. The remaining 43 were split into two
      additional groups. INTERVENTIONS: The first group underwent professional
      cleaning; the second underwent, additionally, scaling and root planing, and the
      third group received no treatment. The fourth and the fifth groups received no
      treatment and professional cleaning, respectively. MAIN OUTCOME MEASURES: O'Leary
      plaque index, Lenox and Kopczyk gingival index, and average gingival overgrowth.
      RESULTS: A significant (P = 0.008) increase in overgrowth was found in the third
      group that did not undergo treatment. Significantly (P = 0.002) less was found in
      the first and second groups. Highly significant (P = 0.001) reductions in the
      plaque and gingivitis indices were also found in these two groups. The fifth
      group showed a highly significant (P = 0.0001) decrease in the plaque and
      gingivitis indices. CONCLUSIONS: Professional cleaning is effective in reducing
      both gingivitis and cyclosporine-induced gingival overgrowth; the combination
      with scaling and root planing reinforces its effectiveness.

PMID- 9282450
TI  - Effectiveness of battery powered light activation units.
AB  - OBJECTIVE: To investigate the effectiveness of chargeable light curing units and
      their ability to sustain a high radiant output following successive discharge
      cycles. SETTING: University based research investigation assessing the output
      intensity of three battery powered light activation units and the effect of
      successive discharge cycles, without intervening periods of recharging, on light
      output and depth of cure of resin composite. MATERIALS AND METHODS: Mean light
      intensity (mW/cm2), through a 4 mm aperture, was measured with a computer based
      radiometer. Two commercially available resin composites (one hybrid and one
      microfilled resin) were used for the depth of cure determinations using a digital
      penetrometer. RESULTS: Depths of cure were significantly greater for the hybrid
      resin composite. Output intensity diminished over the period of battery discharge
      for two of the three units and this finding was paralleled in the depth of cure
      results. The battery light units tested varied significantly with regard to their
      length of discharge cycle and recharge times from complete discharge.
      CONCLUSIONS: Output intensity diminishes over the period of battery discharge for
      some makes of battery light units. However, many other factors including
      handpiece size and weight and unit cost and reliability are important
      considerations when choosing a unit.

PMID- 9282451
TI  - Bacterial endocarditis: results of a survey in a children's hospital in France.
AB  - OBJECTIVE: To identify and analyse the risk factors for infective endocarditis.
      DESIGN: Retrospective survey over a 12-year period. SETTING: Department of
      Paediatric Cardiology, Nancy, France. SUBJECTS: 43 children attending during 1970
      1992 who were diagnosed with infective endocarditis in accordance with Von Reyn's
      classification. RESULTS: 45 episodes of infective endocarditis were recorded (2
      children had 2 episodes). Congenital cardiac disease was the most frequent
      predisposing factor for infective endocarditis. The causes of bacteraemia found
      were frequently, but not exclusively, of dental origin (30.5%). Among the dental
      causes were: poor oral health, inappropriate treatments and lack of antibiotic
      prophylaxis. CONCLUSIONS: Children diagnosed with a cardiac disorder should be
      examined by a dentist. Modern principles of antibiotic therapy and accepted
      dental procedures must be performed as soon as possible and parents informed of
      the current preventive recommendations.

PMID- 9282452
TI  - Instant photography.

PMID- 9282454
TI  - Radiological diagnosis and therapy of pulmonary arteriovenous fistulae in a
      patient with an atypical clinical history: a case report.
AB  - Pulmonary arteriovenous fistulae were first managed nonsurgically by Porstmann in
      1977 with homemade metallic coils (1). During the intervening twenty years better
      catheterization techniques have been developed and our understanding of the
      clinical outcomings of these lesions has improved. This report discusses the
      natural history of pulmonary arteriovenous fistulae, including the neurological
      and other complications, the importance of family screening in the detection of
      asymptomatic family members, the diagnostic strategy and the description of
      improved techniques for embolotherapy with stainless steel coils.

PMID- 9282453
TI  - CASES--clinical audit; scenarios for evaluation and study.
AB  - CASES, an audit and continuing education programme, evaluated aspects of current
      orthodontic practice and allowed orthodontists to identify areas where their
      practice differed from regional and national results. Evaluation of the CASES
      programme verified its value in audit and continuing education and the authors
      hope it will encourage similar projects in other disciplines too.

PMID- 9282455
TI  - Attic cholesteatoma and polyp with a blue ear drum.

PMID- 9282457
TI  - Superiorly-based maxillary sinus polyp.

PMID- 9282458
TI  - Nasal septal anatomy and its importance in septal reconstruction.

PMID- 9282456
TI  - Laryngeal foreign body in a former tracheotomy patient.

PMID- 9282460
TI  - Quality of life analysis of patients undergoing immunotherapy for allergic
      rhinitis.
AB  - Allergic rhinitis has been conservatively estimated to affect 35 million
      Americans, with an annual US expenditure of more than $2 billion for treatment.
      Immunotherapy is generally administered to patients with allergic rhinitis when
      avoidance is impossible or impractical, when pharmacotherapy provides
      insufficient relief, and/or symptoms span more than one season. Immunotherapy
      based on quantified testing (e.g., dilutional intradermal testing [SET] or in
      vitro methods [RAST, ELISA]) allows administration of antigens in a manner that
      achieves therapeutic antigen doses more rapidly, yet more safely than
      immunotherapy administered through a schedule that mixes all antigens at the same
      concentration and advances on an empirical basis. Sixty patients who received at
      least one year of quantified testing-based immunotherapy were evaluated using a
      quality of life questionnaire and individual interviews. Changes in physical,
      social and emotional well-being were determined. Also investigated were changes
      in productivity and medication usage. The majority of patients noted significant
      improvement in all areas within four to six months of initiating immunotherapy,
      and an overwhelming majority felt that such treatment represented a worthwhile
      investment of their time and money.

PMID- 9282459
TI  - Meniere's disease of syphilitic etiology.
AB  - Congenital or acquired syphilis is the cause of Meniere's disease in six percent
      of all cases. The pathogenesis is endolymphatic hydrops and osteitis of the otic
      capsule which produces the characteristic fluctuating hearing loss, tinnitus and
      ear pressure associated with episodic spells of vertigo. The ear symptoms are, at
      first, typical of Meniere's disease of other etiologies. Failure to establish the
      specific etiologic diagnosis can result in unnecessary surgical treatment or
      inappropriate medical therapy. In some cases, if a steroid, the specific
      treatment, is not given promptly, hearing can be quickly and permanently lost.
      The etiology is confirmed by obtaining a reactive fluorescent treponema antibody
      absorption (FTA-abs) test. The clinical features and natural history of Meniere's
      disease of syphilitic etiology are unique. Ear symptoms often begin in the fifth
      decade of life, first in one ear and, after a few years, involving the second
      ear. Reduced or absent caloric responses are characteristic. When hearing loss is
      severe and sudden, this condition represents a true medical emergency and should
      be treated with prompt administration of steroids. An endolymphatic subarachnoid
      shunt operation is occasionally necessary as adjunctive management. An analysis
      of 34 cases shows that long-term use of steroids can maintain effective hearing
      for more than 20 years.

PMID- 9282461
TI  - Pediatric ethmoid mucoceles in cystic fibrosis: long-term follow-up of reported
      cases.
AB  - Ethmoid mucocele, a condition that usually affects adults, can be found in both
      children and infants with cystic fibrosis. We have cared for two patients with
      cystic fibrosis and ethmoid mucoceles. Because we could find no references to the
      prognosis or any long-term follow-up data for this disorder, we contacted the
      physicians and families of six of the seven patients with this condition
      previously reported in the English literature to determine how they were managed
      surgically and the incidence of recurrence. Regardless of the mode of therapy,
      none of the mucoceles recurred.

PMID- 9282462
TI  - Benign pleomorphic adenoma of the larynx: report of a case and review and
      analysis of 20 additional cases in the literature.
AB  - Among the benign pleomorphic adenomas of the minor salivary glands, those that
      develop in the larynx are very rare. One such case of benign pleomorphic adenoma
      of the larynx in an adult female is described. The patient was treated with
      epiglottectomy with a lateral pharyngotomy approach. Review of the literature
      showed an additional 20 well-described cases of benign pleomorphic adenoma of the
      larynx. These patients usually present with hoarseness, dyspnea or dysphagia, or
      any combination of these depending on the site of origin and the size of the
      tumor. Occasionally the tumor may be discovered incidentally. The tumor can occur
      in any part of the larynx with the epiglottis being the most common site.
      Clinically they are indistinguishable from other benign laryngeal neoplasms, as
      surface mucosal lining remains intact. Histopathological examination is used to
      make the definitive diagnosis, but rarely, misinterpretation may occur.
      Conservative surgery provides a lasting cure.

PMID- 9282463
TI  - Effect of basic fibroblast growth factor on perforated chinchilla tympanic
      membranes.
AB  - Basic fibroblast growth factor (bFGF) is a polypeptide mitogen which stimulates
      proliferation of epidermal and connective tissue cells. When applied to tympanic
      membrane perforations it has been reported to enhance healing and produce
      connective tissue hyperplasia. Previous work with animal models has shown that
      hyperplastic alterations of the tympanic membrane play an essential role in
      cholesteatoma development. This study was designed to further investigate the
      hyperplastic effects of bFGF and to determine if it might induce cholesteatoma
      formation during the healing process. Ten chinchillas received bilateral tympanic
      membrane perforations. In each animal, three doses of bFGF (400 nanograms per
      dose) were applied to the perforated tympanic membrane on one side; the opposite
      (control) ear received saline alone. The animals were terminated at either two or
      four weeks and studied histologically. Although the dosage and administration
      schedule used were consistent with previous studies utilizing other rodent
      species, there was little evidence that bFGF affected tympanic membrane healing
      in chinchillas. In both control and bFGF-treated ears, dense connective tissue
      occupied the lamina propria of the tympanic membrane, providing an effective
      barrier against ingrowth of skin toward the middle ear. No cholesteatomas
      developed in any animals included in the study. The results of this work indicate
      that the risk of cholesteatoma formation following administration of bFGF is
      minimal when it is applied short-term to acute perforations.

PMID- 9282464
TI  - A totally implantable drug delivery system for local therapy of the middle and
      inner ear.
AB  - Local therapy of middle and inner ear diseases is being used, but is restricted
      to cases of ear drum perforation or to repeated invasive intratympanic drug
      application by the physician. In accordance with the Medical Device Directive
      (class III), a bone-anchored, totally implantable drug delivery system (TI-DDS)
      has been developed. It includes a micropump for subcutaneous, patient-controlled
      activation, a drug reservoir and a septum port. A thin guide-wired catheter leads
      from the pump outlet to the point of application in the mastoid or middle ear
      cavities. Local inner ear therapy with suitable drugs is possible by positioning
      the catheter's end near the round window membrane. The system requires no battery
      and will offer a wide range of patient-controlled bolus applications (25
      microliters per activation). We first analyzed the three-dimensional implantation
      geometry of the mastoid cavity. Basic micromechanical problems have been solved
      in order to create several prototypes. The TI-DDS has already undergone extensive
      in vitro testing. Recent results of pump rate precision and digital pressure
      force testing are promising. Local drug treatment for conditions such as
      lidocaine-sensitive tinnitus, secretory otitis media, Meniere's disease,
      localized pain and intralesional cancer is under discussion. Furthermore, local
      application of future biotechnological trophic factors for inner ear treatment is
      anticipated. The basic engineering is completed and initial animal tests are in
      preparation.

PMID- 9282466
TI  - Pseudoaneurysm of the right lingual artery: an unusual cause of severe hemorrhage
      during tonsillectomy.
AB  - Profuse intraoperative hemorrhage is an uncommon complication of tonsillectomy.
      We present a three-year-old girl who underwent a routine adenotonsillectomy
      during which massive bleeding occurred from a large vessel in the right tonsillar
      fossae. Angiography revealed an aberrant right lingual artery with a
      pseudoaneurysm. The right lingual artery was embolized with multiple coils and
      the bleeding was halted. The causes and treatment of extracranial carotid artery
      pseudoaneurysms are discussed.

PMID- 9282465
TI  - Subglottic stenosis in Wegener's granulomatosis limited to the head and neck
      region.
AB  - Subglottic stenosis as a complication of Wegener's granulomatosis (WG) is a
      relatively rare lesion and is difficult to treat surgically once stenosis becomes
      sufficiently severe to cause inspiratory dyspnea. Thus, it is important to
      diagnose WG in its early stages to prevent troublesome subglottic stenosis from
      developing by initiating immunosuppressive therapy. The authors report on a 30
      year-old woman suffering from subglottic stenosis of sudden onset due to
      protracted WG limited to the head and neck region. She had had exudative otitis
      media for 13 years and saddle nose and nasal crusting for five years. Repeated
      biopsies of the nasal mucosa and enzyme-linked immunosorbent assays for
      cytoplasmic patterns of antineutrophil cytoplasmic autoantibody (cANCA) had
      failed to establish the diagnosis. However, further histologic examination of the
      nasal mucosa showed vasculitis, and indirect immunofluorescence detected the
      presence of cANCA. Thus, the diagnosis of WG was confirmed 13 years after the
      appearance of the initial symptoms in the ear. The patient was given prednisolone
      (60 mg/day for five days), which greatly relieved the subglottic stenosis. The
      prednisolone dosage was then tapered to 5 mg/day.

PMID- 9282467
TI  - Retrolabyrinthine vestibular nerve section: a current appraisal.
AB  - We report our experience (1987-1993) with Meniere's disease patients treated with
      a retrolabyrinthine vestibular neurectomy. The current literature was reviewed
      and our results have been compared with those of previous reports. The overall
      success rate for vertigo relief was 96.7%, with no serious or permanent
      complications resulting from the procedure. The technical elements of the
      operation, as they apply to our approach and those of others, have been analyzed,
      with special attention given to the anatomical features of the region and their
      influence on success or failure. We conclude that the retrolabyrinthine approach
      for vestibular nerve section remains a safe and highly successful technique which
      merits continued use.

PMID- 9282468
TI  - Immunologic evaluation of the child with recurrent otitis media.

PMID- 9282469
TI  - A multifactorial analysis of facial nerve results in surgery for cerebellopontine
      angle tumors.

PMID- 9282471
TI  - Modeling and estimation of single evoked brain potential components.
AB  - In this paper, we present a novel approach to solving the single-trial evoked
      potential estimation problem. Recognizing that different components of an evoked
      potential complex may originate from different functional brain sites and can be
      distinguished according to their respective latencies and amplitudes, we propose
      an estimation approach based on identification of evoked potential components on
      a single-trial basis. The estimation process is performed in two stages: first,
      an average evoked potential is calculated and decomposed into a set of
      components, with each component serving as a subtemplate for the next stage;
      then, the single measurement is parametrically modeled by a superposition of an
      emulated ongoing electroencephalographic activity and a linear combination of
      latency and amplitude-corrected component templates. Once optimized, the model
      provides the two assumed signal contributions, namely the ongoing brain activity
      and the single evoked brain response. The estimator's performance is analyzed
      analytically and via simulation, verifying its capability to extract single
      components at low signal-to-noise ratios typical of evoked potential data.
      Finally, two applications are presented, demonstrating the improved analysis
      capabilities gained by using the proposed approach. The first application deals
      with movement related brain potentials, where a change of the single evoked
      response due to external loading is detected. The second application involves
      cognitive event-related brain potentials, where a dynamic change of two
      overlapping components throughout the experimental session is detected and
      tracked.

PMID- 9282470
TI  - Micromodular implants to provide electrical stimulation of paralyzed muscles and
      limbs.
AB  - We describe the design, fabrication, and output capabilities of a microminiature
      electrical stimulator that can be injected in or near nerves and muscles. Each
      single-channel microstimulator consists of a cylindrical glass capsule with
      hermetically sealed electrodes in either end (2-mm diameter x 13-mm overall
      length). Power and digital control data can be transmitted to multiple implants
      (256 unique addresses) via a 2-MHz RF field created by an external AM oscillator
      and inductive coil. In vitro testing demonstrated accurate control of output
      pulsewidth (3-258 microseconds in 1-microseconds steps) and current (0-30 mA in
      two linear ranges of 16 steps each, up to 8.5 V available compliance voltage).
      Microstimulators were used successfully for chronic stimulation in hindlimb
      muscles of cats. Design and fabrication issues affecting yield and reliability of
      the packaging and electronics are discussed.

PMID- 9282472
TI  - New finite difference formulations for general inhomogeneous anisotropic
      bioelectric problems.
AB  - Due to its low computational complexity, finite difference modeling offers a
      viable tool for studying bioelectric problems, allowing the field behavior to be
      observed easily as different system parameters are varied. Previous finite
      difference formulations, however, have been limited mainly to systems in which
      the conductivity is orthotropic, i.e., a strictly diagonal conductivity tensor.
      This in turn has limited the effectiveness of the finite difference, technique in
      modeling complex anatomies with arbitrarily anisotropic conductivities, e.g.,
      detailed fiber structures of muscles where the fiber can lie in any arbitrary
      direction. In this paper, we present both two-dimensional and three-dimensional
      finite difference formulations that are valid for structures with an
      inhomogeneous and nondiagonal conductivity tensor. A data parallel computer, the
      connection machine CM-5, is used in the finite difference implementation to
      provide the computational power and memory for solving large problems. The finite
      difference grid is mapped effectively to the CM-5 by associating a group of nodes
      with one processor. Details on the new approach and its data parallel
      implementation are presented together with validation and computational
      performance results. In addition, an application of the new formulation in
      providing the potential distribution inside a canine torso during electrical
      defibrillation is demonstrated.

PMID- 9282473
TI  - Imaging of fluorescence in highly scattering media.
AB  - Two one-speed radiation transport equations coupled by a dynamic equation for the
      distribution of fluorophore electronic states are used to model the migration of
      excitation photons and emitted fluorescence photons. The conditions for producing
      appreciable levels of fluorophore in the excited state are studied, with the
      conclusion that minimal saturation occurs under the conditions applicable to
      tissue imaging. This simplifies the derivation of the frequency response and of
      the imaging operator for a time-harmonic excitation source. Several factors known
      to influence the fluorescence response-the concentration, mean lifetime and
      quantum yield of the fluorophore, and the modulation frequency of the excitatory
      source-are examined. Optimal sensitivity conditions are obtained by analyzing the
      fluorescence source strength as a function of the mean lifetime and modulation
      frequency. The dependence of demodulation of the fluorescent signal on the above
      factors is also examined. In complementary studies, transport-theory-based
      operators for imaging fluorophore distributions in a highly scattering medium are
      derived. Experimental data were collected by irradiating a cylindrical phantom
      containing one or two fluorophore-filled balloons with continuous wave laser
      light. The reconstruction results show that qualitatively and quantitatively good
      images can be obtained, with embedded objects accurately located and the
      fluorophore concentration correctly determined.

PMID- 9282474
TI  - A method of ultrasonic 3-D computed velocimetry.
AB  - A method of ultrasonic three-dimensional (3-D) vector velocimetry, which is
      derived by extending the previously proposed two-dimensional (2-D) vector
      velocimetry, is presented. In the proposed method, the three vector components of
      velocity to be measured are defined as the velocity in the beam axial direction,
      and angle velocities in two transverse directions. To derive the three components
      of velocity, signals detected by a 2-D array transducer are first 2-D Fourier
      transformed in the spatial domain parallel to the 2-D array transducer and then
      are one-dimensional (1-D) Fourier transformed in the time domain. The advantage
      of the proposed method is that it uses a linear signal processing, so it can
      simultaneously measure individual velocities of multiple scatterers. Computer
      simulations clearly demonstrate the effectiveness of the proposed method.

PMID- 9282475
TI  - A spark counter as a control unit of a radio frequency surgery device.
AB  - A new approach in radio frequency (rf) electrosurgery, used for tissue treatment,
      is achieved by using a new process control method. An external control unit
      allows a commonly available rf-generator to automatically supply the appropriate
      power for differing tissue types, thus ensuring best cutting quality. The sparks,
      generated during the scalpel electrode interaction with the tissue, appear
      statistically distributed. The spark rate depends on various factors and is
      monotonic with the supplied electrical power. This allows it to be used as the
      controlled variable in the cutting process. The ac current passing through the
      tissue is evaluated by an external control unit using an analyzation algorithm to
      determine the number of sparks. The external unit is comprised of a system, which
      measures the spark rate, and a subsequent proportional integral (P.I.)
      controller. The functionality of the control method as well as the electrical
      circuitry is verified through cuts with different degrees of carbonization and
      cuts through tissue heterojunctions.

PMID- 9282477
TI  - MSE behavior of biomedical event-related filters.
AB  - The mean-squared error (MSE) behavior for Fourier linear combiner (FLC)-based
      filters is analyzed, using the independence assumption. The advantage of this
      analysis is its simplicity compared with previous results. The MSE transient
      behavior for this kind of filters is also presented for the first time. Moreover,
      a time-varying sequence for the least mean square (LMS) algorithm step-size is
      proposed to provide fast convergence with small misadjustment error. It is shown
      that for this sequence, the MSE behaves better as the input signal-to-noise ratio
      (SNR) decreases, but increases with the number of harmonics. Lastly, we make a
      brief analysis on the nonstationary behavior of these filters, and again we find
      simple expressions for the MSE behavior.

PMID- 9282476
TI  - Noise covariance incorporated MEG-MUSIC algorithm: a method for multiple-dipole
      estimation tolerant of the influence of background brain activity.
AB  - This paper proposes a method of localizing multiple current dipoles from spatio
      temporal biomagnetic data. The method is based on the multiple signal
      classification (MUSIC) algorithm and is tolerant of the influence of background
      brain activity. In this method, the noise covariance matrix is estimated using a
      portion of the data that contains noise, but does not contain any signal
      information. Then, a modified noise subspace projector is formed using the
      generalized eigenvectors of the noise and measured-data covariance matrices. The
      MUSIC localizer is calculated using this noise subspace projector and the noise
      covariance matrix. The results from a computer simulation have verified the
      effectiveness of the method. The method was then applied to source estimation for
      auditory-evoked fields elicited by syllable speech sounds. The results strongly
      suggest the method's effectiveness in removing the influence of background
      activity.

PMID- 9282478
TI  - Wavelet image extension for analysis and classification of infarcted myocardial
      tissue.
AB  - Some computer applications for tissue characterization in medicine and biology,
      such as analysis of the myocardium or cancer recognition, operate with tissue
      samples taken from very small areas of interest. In order to perform texture
      characterization in such an application, only a few texture operators can be
      employed: the operators should be insensitive to noise and image distortion and
      yet be reliable in order to estimate texture quality from the small number of
      image points available. In order to describe the quality of infarcted myocardial
      tissue, we propose a new wavelet-based approach for analysis and classification
      of texture samples with small dimensions. The main idea of this method is to
      decompose the given image with a filter bank derived from an orthonormal wavelet
      basis and to form an image approximation with higher resolution. Texture energy
      measures calculated at each output of the filter bank as well as energies of
      synthesized images are used as texture features in a classification procedure. We
      propose an unsupervised classification technique based on a modified statistical
      t-test. The method is tested with clinical data, and the classification results
      obtained are very promising. The performance of the new method is compared with
      the performance of several other transform-based methods. The new algorithm has
      advantages in classification of small and noisy input samples, and it represents
      a step toward structural analysis of weak textures.

PMID- 9282479
TI  - Localization of brain electrical activity via linearly constrained minimum
      variance spatial filtering.
AB  - A spatial filtering method for localizing sources of brain electrical activity
      from surface recordings is described and analyzed. The spatial filters are
      implemented as a weighted sum of the data recorded at different sites. The
      weights are chosen to minimize the filter output power subject to a linear
      constraint. The linear constraint forces the filter to pass brain electrical
      activity from a specified location, while the power minimization attenuates
      activity originating at other locations. The estimated output power as a function
      of location is normalized by the estimated noise power as a function of location
      to obtain a neural activity index map. Locations of source activity correspond to
      maxima in the neural activity index map. The method does not require any prior
      assumptions about the number of active sources of their geometry because it
      exploits the spatial covariance of the source electrical activity. This paper
      presents a development and analysis of the method and explores its sensitivity to
      deviations between actual and assumed data models. The effect on the algorithm of
      covariance matrix estimation, correlation between sources, and choice of
      reference is discussed. Simulated and measured data is used to illustrate the
      efficacy of the approach.

PMID- 9282480
TI  - Analysis of pattern reversal visual evoked potentials (PRVEP's) by spline
      wavelets.
AB  - In this study, the pattern-reversal visual evoked potentials (PRVEP's) collected
      from normal and demented subjects are investigated by applying the quadratic
      spline wavelet analysis. The data are decomposed into six octave frequency bands.
      For quantitative purposes, the wavelet coefficients in the residual waveform
      representing the delta-theta band activity (0-8 Hz) are explored to characterize
      the (N70-P100-N130) complex. Specifically, the coefficients corresponding to the
      location of N70, P100, and N130 peaks are investigated for their sign in order to
      test whether they represent a consistent (N70-P100-N130) complex in the averaged
      waveform. Waveforms with normal latency (N70-P100-N130) complex are observed to
      have positive second, negative third, and positive fourth coefficients in
      amplitude in their residual scale standing for the delta-theta (0-8 Hz) band
      activity. The method allows for the analysis of oscillatory-phase behavior of the
      normal and pathological PRVEP's in their delta-theta band based on a few
      quantitative measures consistent with the time-frequency occurrence of the major
      components of the evoked potential.

PMID- 9282481
TI  - A patient-adaptable ECG beat classifier using a mixture of experts approach.
AB  - We present a "mixture-of-experts" (MOE) approach to develop customized
      electrocardiogram (ECG) beat classifier in an effort to further improve the
      performance of ECG processing and to offer individualized health care. A small
      customized classifier is developed based on brief, patient-specific ECG data. It
      is then combined with a global classifier, which is tuned to a large ECG database
      of many patients, to form a MOE classifier structure. Tested with MIT/BIH
      arrhythmia database, we observe significant performance enhancement using this
      approach.

PMID- 9282482
TI  - Designing better adaptive sampling algorithms for ECG Holter systems.
AB  - Let psi be any adaptive sampling algorithm that can run in real time on a
      tapeless multichannel electrocardiogram (ECG) Holter system. Simple methods which
      can significantly improve psi's fidelity are described and their results are
      compared in this paper. It is shown that by adding some simple tests to psi, the
      signals reconstructed by psi can be improved as much as 5.45 dB. It is also shown
      that under the same data rate, a good data compressor with slowly sampled input
      ECG is preferable to a bad data compressor with highly sampled input ECG.

PMID- 9282483
TI  - Elimination of interference component in Wigner-Ville distribution for the signal
      with 1/f spectral characteristic.
AB  - A new technique for interference-term suppression in Wigner-Ville distribution
      (WVD) is proposed for the signal with 1/f spectrum shape. The spectral
      characteristic of the signal is altered by f alpha filtering before time
      frequency analysis and compensated after analysis. With the utilization of the
      proposed technique in smoothed pseudo Wigner-Ville distribution, an excellent
      suppression of interference component can be achieved.

PMID- 9282484
TI  - ICDS--past, present and future.

PMID- 9282485
TI  - Juvenile dermatomyositis in north India.
AB  - OBJECTIVE: To determine the clinical profile and therapeutic response of patients
      with juvenile dermatomyositis (JDM). DESIGN: Hospital based descriptive follow-up
      study. SAMPLE: 12 patients attending the Pediatric Rheumatology and Immunology
      Clinic over last five years. RESULTS: The patients were aged between 3 1/2 years
      to 12 years with a male to female ratio of 2:1. All patients had proximal muscle
      weakness at presentation. Distal muscle weakness and masseter atrophy was seen in
      2 patients and neck flexor weakness and pharyngeal weakness was seen in 1 case.
      Muscle pain, tenderness or swallowing difficulties were not observed. Classical
      skin manifestations of JDM were present in all except one patient. Vasculitic
      lesions were not noted. One patient had diffuse lipoatrophy. Two patients
      developed calcinosis cutis while on treatment. All patients were put on oral
      corticosteroids (prednisolone 2 mg/kg/day) initially which were gradually tapered
      while monitoring clinical response. Early initiation of steroid therapy resulted
      in an excellent response. Two patients who did not show significant improvement
      even with prolonged steroid therapy were given oral weekly methotrexate (10
      mg/m2/week). CONCLUSIONS: Most of the children with JDM showed good response to
      steroid therapy which needs to be continued for a prolonged period. Children who
      do not respond to this therapy may be given oral weekly methotrexate.

PMID- 9282486
TI  - Brainstem auditory evoked response in neonates with birth asphyxia.
AB  - OBJECTIVE: To determine the brainstem auditory evoked response (BAER)
      abnormalities and their reversibility in neonates with birth asphyxia. DESIGN:
      Prospective case control study. SETTING: Tertiary care teaching hospital.
      METHODS: 30 term Neonates with 5-min Apgar < 6 and hypoxic ischemic
      encephalopathy (HIE) underwent BAER testing with follow up at 3 months. An equal
      number of normal term neonates served as controls. RESULTS: 13 out of 30 (43.3%)
      neonates with birth asphyxia showed some abnormality in BAER wave form. The
      commonest type of BAER abnormalities seen were transient prolongation of
      latencies of various waves (69.2%) and prolonged interside latency difference
      (69.2%). Other abnormalities observed were prolonged interwave interval (23.1%)
      and prolonged interside interval difference (7.7%). Abnormalities in BAER were
      significantly associated with stages of HIE and duration of neurological
      abnormalities more than 5 days. On follow up of 16 cases at 3 months of age, BAER
      abnormalities reverted back to normal in all the neonates. The Denver
      Developmental Screening Test (DENVER II) was suspect in 4 cases but the BAER was
      normal. CONCLUSION: BAER abnormalities in asphyxic neonates are transient and
      revert back to normal at 3 months of age. BAER does not appear to be a useful
      tool for early detection of neurological handicaps.

PMID- 9282487
TI  - Perinatal asphyxia: multivariate analysis of risk factors in hospital births.
AB  - OBJECTIVE: To determine risk factors for perinatal asphyxia. DESIGN: Cohort
      study. SETTING: Teaching hospital. METHODS: All consecutive hospital births were
      evaluated during the study period. Asphyxia was defined on intrapartum and
      neonatal resuscitation criteria. Maternal, intrapartum and neonatal variables
      were recorded in all births. Data was analyzed after stratifying for live and
      stillbirths by univariate and logistic regression analyses. RESULTS: Amongst 2371
      births (55 fetal deaths and 2316 live births), there were 86 cases of perinatal
      asphyxia (35 fetal deaths and 51 live births), providing an asphyxia rate of
      36.3/1000 births. On multivariate analysis, risk factors significantly associated
      with asphyxia included prolonged second stage labor (OR 9.4), vaginal breech
      delivery (OR 6.6), elective cesarean delivery (OR 4.6), pregnancy induced
      hypertension (PIH) (OR 2.7) and fetal growth retardation (SFD) (OR 2.4). Amongst
      stillborn, the significant univariate factors associated with asphyxia were
      prolonged second stage labor (RR 1.7) and cord prolapse (RR 1.7). CONCLUSIONS:
      There is a need to strengthen intrapartum management and early identification of
      mothers with PIH or intrauterine growth retardation to reduce asphyxial morbidity
      and mortality.

PMID- 9282489
TI  - Infantile spasms.

PMID- 9282490
TI  - Options: academic and/or otherwise.

PMID- 9282488
TI  - Predictors of mortality in subjects hospitalized with acute lower respiratory
      tract infections.
AB  - OBJECTIVE: To identify the predictors of mortality due to acute lower respiratory
      tract infection (ALRI). DESIGN: Prospective cohort study. SETTING: Urban tertiary
      care teaching hospital. METHODS: 201 cases with ALRI between 2 weeks to 5 years
      of age were prospectively enrolled and followed up to determine outcome. Detailed
      history and clinical evaluation were recorded on a pretested proforma.
      Significant independent predictors of mortality were determined by comparison of
      dead subjects (n = 21) with surviving children (n = 180) in a multiple logistic
      analytic framework. RESULTS: The case fatality rate (CFR) was 10.45%. Significant
      independent predictors of mortality were (OR, 95% CI) age less than 1 year (23.1,
      2.7-197.5), inability to feed (6.2, 1.3-30.7), associated loose stools (5.1,1.2
      27.3), weight for age Z score < -3 (3.9,1.01-9.7), short duration of fever
      (1.2,1.0-1.5) and bandemia (1.1,1.05-1.2). The WHO guidelines identified 91% of
      children diagnosed as ALRI by clinical and investigative criteria. The CFR was
      related to severity of WHO classification ("pneumonia"-0%, "severe pneumonia"
      8.7% and "very severe pneumonia"-47.0%). However, 2 of the 18 subjects with a
      diagnosis of "no pneumonia" expired (CFR 11.1% and 10% of total mortality).
      CONCLUSION: Even in settings of high case fatality, predictors of mortality can
      be identified in under five children suffering from ALRI. In this context, age
      below 1 year, inability to feed, presence of loose stools and severe malnutrition
      merit attention for interventional purposes.

PMID- 9282491
TI  - Endemic fluorosis with genu valgum syndrome in a village of district Mandla,
      Madhya Pradesh.

PMID- 9282493
TI  - Relevance of performing a 'sepsis screen' in a surgical neonate.

PMID- 9282492
TI  - Zinc supplementation in severe malnutrition.

PMID- 9282495
TI  - Post transfusion purpura in a thalassemic child.

PMID- 9282494
TI  - General and reproductive health of adolescent girls in rural south India.

PMID- 9282496
TI  - Melanotic neuroectodermal tumor of infancy.

PMID- 9282497
TI  - Achalasia cardia in an infant.

PMID- 9282498
TI  - Juvenile diabetes mellitus masquerading as disseminated candidiasis.

PMID- 9282499
TI  - Recurrent pain abdomen due to biliary calculus.

PMID- 9282501
TI  - Parenteral iron therapy: indications and safety.

PMID- 9282500
TI  - Beckwith-Wiedemann syndrome.

PMID- 9282502
TI  - Micronutrient malnutrition--half of the world's population affected.

PMID- 9282503
TI  - Disseminated BCG infection.

PMID- 9282504
TI  - Sucrose: is it not only sweet, but also an analgesic?

PMID- 9282505
TI  - Efficacy of sodium antimony gluconate and ketoconazole in the treatment of kala
      azar--a comparative study.
AB  - The present study was undertaken to determine the efficacy of ketoconazole in
      comparison to sodium antimony gluconate (SAG) in the treatment of kala-azar. The
      study was conducted at two centres: All India Institute of Medical Science, New
      Delhi and Calcutta School of Tropical Medicine, Calcutta. A total of 180 patients
      with proven kala-azar were recruited. After preliminary investigations, the
      patients were randomly divided into 2 groups: One group received ketoconazole in
      a dose of 600 mg/ day in 3 divided doses for 4 weeks while the other group was
      treated with SAG at a dose of 20 mg/kg/day up to a maximum of 850 mg/day for 4
      weeks. The patients were followed up by clinical examination, liver functions,
      haemogram and the bone marrow/splenic aspiration. Responders were followed up at
      3 and 9 months of intervals. Of 90 cases in SAG, 78 (81.7%) got cured initially
      while under ketoconazole group, only 26 (33.3%) of 78 patients responded
      initially (p < 0.001). After 3 months of follow up, 75 of 78 SAG-responders
      (96.2%) and 24 of 26 ketoconazole-responders (92.3%) continued to be in
      remission. Despite the fact that 2 patients in each group were lost to follow up
      at 9 months, similar observations were noted with only one relapse in SAG group.
      The response to SAG was comparable at the two centres. However, the response to
      ketoconazole was better at Delhi centre as compared to that at Calcutta. There
      were no significant side effects or hormonal changes in any of the patients in
      ketoconazole group at Delhi centre. Significantly higher side effects were
      reported at Calcutta centre in ketoconazole group (P < 0.05). No satisfactory
      explanation can be given for this difference in response to ketoconazole at two
      centres. However, it is known that leishmanial parasites of different
      geographical origin differ in their response to different drugs and this could be
      one of the reasons for difference observed in response rate to ketoconazole as
      the study involved different populations of people.

PMID- 9282506
TI  - Seroprevalence of cytomegalovirus antibodies in patients attending STD and
      antenatal clinics.
AB  - Sera from 368 patients attending sexually transmitted disease (STD) and antenatal
      clinics were screened for cytomegalovirus (CMV) specific IgG and IgM by indirect
      ELISA. IgG was detected in 94% of patients tested. CMV IgM seropositivity was
      found in 8.5% of normal pregnant females and in none of the normal asymptomatic
      males. CMV-IgM was detected in higher number of patients with STD than in those
      without STD. There was slightly higher association of CMV IgM antibodies mainly
      with syphilis in males and chlamydial endocervicitis in females.

PMID- 9282508
TI  - Some pathogenic fungi involved in serious cases of urinary tract infections in
      Nigeria.
AB  - Three hundred early morning midstream urine samples collected from 200 females
      and 100 males between the ages of 20 and 60 years, suffering from urinary tract
      infections (UTI) were studied to determine the etiologic agents. The caliberated
      loop-direct method used for culturing each sample on both bacterial and fungal
      media showed significant microbial growth in 117 of the 300 samples. Bacteria
      were the sole agents of infection in 30% of the cases while pathogenic yeasts
      were the sole agents of infection in 8% of the cases. Only 1% showed mixed
      infection. The bacterial pathogens identified from the culture were Escherichia
      coli (12.7%), Staphylococcus aureus (8.0%), Proteus mirabilis (4.3%), Klebsiella
      aerogenes (2.7%), Streptococcus faecalis (2.0%) and Pseudomonas aeruginosa
      (0.3%). The fungal pathogens isolated were Candida albicans (0.3%). While
      patients between the ages of 20 and 40 years were significantly more susceptible
      to UTI caused by bacteria (P = 0.05), patients between the ages of 41 and 60
      years were more prone to UTI caused by fungi. Also females appeared to contact
      UTI more often than males.

PMID- 9282507
TI  - In vitro antiviral activity of indigenous glycyrrhizin, licorice and glycyrrhizic
      acid (Sigma) on Japanese encephalitis virus.
AB  - Glycyrrhizin, a triterpenoid glycoside and Licorice from Glycyrrhiza glabra and
      Ammonium salt of Glycyrrhizic acid (Sigma) were tested for antiviral activity on
      three strains of Japanese encephalitis virus (JEV), Nakayama, P-20778 and 821564
      XY48. Purified glycyrrhizin (M.w. 822.92) inhibited plaque formation in all the
      three strains of JEV at a concentration of 500 micrograms/ml at 96 hrs, Similar
      effect was observed at 1000 micrograms/ml concentration with Licorice and
      Ammonium salt of glycyrrhizic acid. The minimal inhibitory concentrations were
      not toxic to porcine stable kidney (PS) and human cervical carcinoma (HeLa) cell
      lines. Cyctotoxicity of these chemicals was evaluated by trypan blue dye
      exclusion test which indicated subtoxic concentrations at 5,000 micrograms/ml at
      96 hrs and toxic concentrations were 10,000 micrograms/ml at the same time period
      for the host cells PS. Thus the indigenously purified glycyrrhizin seems to be
      more potent antiviral agent than Licorice and ammonium salt of glycyrrhizic acid
      (Sigma) for JEV 'in vitro'.

PMID- 9282509
TI  - Biting behaviour and biting rhythm of potential Japanese encephalitis vectors in
      Assam.
AB  - Studies on biting behaviour and biting cycles of medically important mosquitoes
      were carried out in Madhupur village and Tarajan tea estate of upper Assam.
      Collections were made off human baits outdoors and indoors and off cattle bait
      outdoors from August 1991 to July 1992. Human bait collections were performed
      using the 'stationary direct bait' technique. A total of 9,072 adult host seeking
      female mosquitoes representing 26 species and 5 genera were collected off baits
      of which 36.9% were collected off human baits and the rest from cattle. All
      mosquitoes were primarily zoophilic, although significant numbers were collected
      biting man outdoors. Biting preferences of important Japanese encephalitis (JE)
      vectors for man and cattle were studied using outdoor man:outdoor cattle ratio
      (attraction ratio = AR). Culex quinquefasciatus was attracted towards human baits
      the most (AR = 8.1:1), followed by Cx. bitaeniorhynchus (AR = 1.6:1) and Mansonia
      annulifera (AR = 1.3.1). The hourly biting activity of important JE vectors
      throughout the night on two bait types was also studied using three point moving
      averages. Hierarchical agglomerative cluster analysis was used to compare and
      classify mosquitoes on the basis of their similarity in biting rhythms.

PMID- 9282510
TI  - V. cholerae 01 outbreak in remote villages of Shimla district, Himachal Pradesh,
      1994.
AB  - An outbreak of V. cholerae 01 occurred in remote villages of Rohru tehsil,
      district Shimla, Himachal Pradesh, during June-July 1994. Seven villages were
      affected. Overall attack rate was 16.4 per cent in surveyed villages. Attack rate
      in children < 5 was significantly high. Suspected source was spring water
      contaminated from open air defaecation. V. cholerae was resistant to co
      trimoxazole and streptomycin.

PMID- 9282512
TI  - Sero-prevalence of brucellosis among abattoir personnel of Delhi.
AB  - A total of 165 serum samples of abattoir personnel of Delhi were tested by Rose
      Bengal Plate test (RBPT), Standard tube agglutination test (STAT), Complement
      fixation test (CFT) and Dot-Enzyme linked immunosorbent assay (Dot-ElISA). The
      Seroprevalence was 20.60, 12.75, 50.30 and 25.45 percent, respectively on the
      basis of RBPT, STAT, CFT and Dot-ELISA. Seroprevalence was highest among blood
      collectors (99.77%) followed by miscellaneous group (72%), animal handlers
      (68.96%), butchers (68.00%) and sweepers (57.14%). Among veterinarians,
      Seroprevalance was 28.57%. The Seroprevalence was more among persons of higher
      age group. The study indicates that abattoir personnel are at high risk to
      infection with brucellosis.

PMID- 9282511
TI  - Immunization coverage among urban and rural children in the Shimla hills.
AB  - A cross sectional study was carried out to assess immunisation coverage among 257
      urban and 339 rural children aged 13-36 months who were vaccinated at pulse polio
      booths in Shimla hills. 84.37% urban children and 57.59% rural children were
      fully vaccinated. BCG scar was negative in a large number of children, especially
      from rural areas. Increasing maternal education was associated with complete
      immunisation. OPV I-III dropouts were 3% among urban children and 15% among
      rural. The corresponding dropout rates for DPT I-III were 1% and 8% respectively.
      The immunisation coverage in this region was higher than others. Sustained
      efforts are required to achieve full immunisation coverage and eradicate polio
      and measles.

PMID- 9282513
TI  - Knowledge and attitudes of pregnant women regarding AIDS in a semi arid area of
      Rajasthan.
AB  - A total of 792 pregnant women from three hospitals of Jaipur were surveyed to
      assess and compare their knowledge and attitudes regarding various aspects of
      AIDS. Observations revealed that level of knowledge was significantly higher in
      pregnant women from upper income group than low income group (P < 0.05). The
      misconceptions regarding various aspects of AIDS viz. symptoms and signs,
      transmission and prevention and opinion towards the AIDS patients, indicate that
      there is strong need of AIDS education compaign in pregnant women too.

PMID- 9282514
TI  - Status of Plasmodium falciparum resistance to chloroquine in Orissa.
AB  - Orissa is known for its contribution of 15-20% of malaria cases to the national
      total. Deaths due to malaria in the state are also not uncommon. Proportion of P.
      falciparum cases have reached to 85%. In the recent years over 0.3 million
      confirmed malaria cases have been reported each year. Annual consumption of
      chloroquine in the state is over 170 lakh tablets. A 17 year study on monitoring
      of choloroquine resistance in P. falciparum in Orissa revealed that out of a
      total of 1165 tests conducted in vivo, in 12% of the cases RI level of resistance
      was detected. And 4.4% cases were of RII and 1.9% RIII level. 51% of the sample
      tested in vitro showed P. falciparum resistance to chloroquine. P. falciparum
      resistance to chloroquine appears to have been developed by the parasite over the
      length and breadth of the state. Strengthening of the monitoring of drug
      resistance in P. falciparum in the state is indicated.

PMID- 9282515
TI  - Breeding habitats of vector sandflies and their control in India.
AB  - In India Phlebotomus argentipes and Phlebotomus papatasi are the proven and
      suspected vectors of visceral leishmaniasis respectively. In the past, only a few
      samples from the field yielded sandfly immatures though there were many adults in
      the vicinity. This might be because of dearth of information on the various
      factors influencing the oviposition of the gravid females as well as survival and
      development of immatures. Therefore, available information on these aspects has
      been reviewed so as to highlight the imperative of undertaking further studies on
      the ecology of immatures in field conditions.

PMID- 9282516
TI  - Human distomatosis due to Fasciola hepatica infection in Assam, India.
AB  - A seven year old girl in a rural area of Upper Assam was found to be infected
      with Fasciola hepatica. The girl gave history of eating watercress. Besides the
      presence of eggs in the stools, her liver was enlarged and tender. Liver function
      tests revealed hepato-biliary involvement with increase in serum AKP and ALT.
      Ultrasonography revealed presence of adult fluke in gall bladder, and a marginal
      thickening of gall bladder wall. However, the echo pattern of her liver
      parenchyma was normal. The case is reported for its public health significance
      and is a maiden report from north eastern India.

PMID- 9282518
TI  - First outbreak of Dengue fever in a typical rural area of Haryana state in
      northern India.

PMID- 9282517
TI  - An outbreak of acute conjunctivitis due to coxsackie A24 virus in Delhi.

PMID- 9282519
TI  - A study to evaluate the impact of different dose/frequency of temephos 50% ec for
      control of Cx. quinquefasciatus vector of bancroftian filariasis.

PMID- 9282520
TI  - Changing malaria endemicity--a village based study in Sonitpur, Assam.

PMID- 9282521
TI  - Malaria epidemic in Lamta PHC of Balaghat district--a rice cultivating ecosystem.

PMID- 9282522
TI  - HCV activity in Calcutta--a serological study.
AB  - HCV infection, a global public health problem is quite prevalent in India. In the
      present study conducted during February-July 1996 a total of 153 samples of
      different age groups and of both sexes were tested by ELISA for detection of Anti
      HCV antibody. Anti-HCV was found in 13% of multi-transfused cases and in 8.8%
      cases with multiple needle-stick injury. Maximum seropositivity (20%) could be
      observed amongst males between 31-40 yrs. age group. HCV activity was noted more
      in males (13%) than in females (8.2%) and more relatively in subjects without a
      history of jaundice (11.5%) than those having the features of jaundice (10.5%).
      An increasing trend has also been observed amongst the multi-transfused cases in
      Calcutta.

PMID- 9282524
TI  - Changing patterns of Vibrio cholerae isolation over three consecutive cholera
      seasons (1992-1994) in east Delhi.
AB  - The emergence of new strains of Vibrio Cholerae has added a new dimension to the
      variability in pathogenicity and potential virulence of the organisms
      precipitating diarrhoeal diseases. Considering the shifting patterns of V.
      cholerae 01 there is a continuous need to monitor the strain characteristics. In
      this study total 541 stool specimens of acute secretory diarrhoea were
      investigated between May 1992 and November 1994 for strains of Vibrio Cholerae
      and anti-microbial susceptibility testing of all the confirmed V. Cholerae
      strains. In 1992, 50 of the 125 strains (40%) were positive for V. cholerae 01
      predominantly biotype El Tor serotype ogawa, and 10 (80%) of non 01 type, with
      most strains susceptible to tetracycline (100%), chloramphenicol (98%) and
      Cotrimoxazole (98%), but all resistant to polymyxin B and furazolidine. In 1993,
      44 (43.6%) of the 010 strains were positive for V. cholerae 0139 and the rest V.
      cholerae 01. In 1994, another sero group of V. cholerae 010 emerged, with 42
      (13.3%) being positive. Isolates did not agglutinate with any of these antisera
      and have been labelled as 'other than non-01 vibrio cholerae'.

PMID- 9282525
TI  - Five-year longitudinal study of efficacy and safety of purified Vero cell rabies
      vaccine for post-exposure prophylaxis of rabies in Indian population.
AB  - Three hundred and nine (309) persons, vaccinated against rabies with Purified
      Vero-cell Rabies (PVR) vaccine from 1991-1995, were included in this five-year
      longitudinal study. This study was conducted to observe the consistency,
      immunogenicity, inocuity, safety and efficacy of this vaccine under field
      conditions. All the 309 persons attended our centre after taking post-exposure
      vaccination following bites by suspected rabid animals or contact with
      hydrophobia patients for antirabies antibody titre estimation. The vaccine was
      very well tolerated by vaccinees with only 7 per cent, complaining of mild to
      moderate side reactions. On an average, every year 70-100 vaccinees reported at
      this centre after PVR vaccination. The epidemiological characteristics of rabies
      based on above data are also discussed in this paper. Serological response, i.e.,
      antirabies antibody titre following vaccination in all these persons were found
      to be satisfactory with mean antibody titre of 4.25 I.U./ml.

PMID- 9282523
TI  - Risk behavioural practices of rural mothers as determinants of childhood
      diarrhoea.
AB  - Maternal behaviours related to certain child care practices which possibly have a
      contributory role in causation of diarrhoea in children were studied. Comparison
      was made between behaviours of mothers in 108 families having diarrhoeal children
      (Case families) with mothers of 72 families having age and neighbourhood matched
      non diarrhoeal children (control families) using a logistic regression model.
      Five risk behaviours were identified and these are bottle feeding (OR-2.87; CI
      1.30 to 6.34), non-use of soap for cleaning feeding container (OR-2.61; CI-1.30
      to 5.23), water storage in wide-mouthed container (OR-2.75; CI-1.27 to 5.96), use
      of pond water for the same (OR-2.36; CI-1.15 to 4.84) and indiscriminate disposal
      of children's stool (OR-1.99; CI-0.97 to 4.08). Around 83 per cent of diarrhoeal
      families could be predicted using these five variables only. The first three of
      these five risk behaviours were responsible for occurrence of significantly
      higher incidence (3 or more episodes) of diarrhoea in the case families. All
      these risk behaviours are amenable to change if suitable intervention is
      initiated. The result of this study would be helpful in reducing diarrhoea
      associated morbidity to a substantial level.

PMID- 9282526
TI  - Cryptosporidium in AIDS patients in south India: a laboratory investigation.
AB  - Faecal samples from 108 AIDS patients submitted for parasitological examination
      were screened for Cryptosporidium oocysts. Twenty-four were symptomatic patients
      (Group I), 40 mildly symptomatic (Group II) and 47 asymptomatic (Group III).
      Cryptosporidium was present in faecal samples of four out of twelve diarrhoeic
      AIDS patients. None in other groups were positive for Cryptosporidium.
      Concentration of faeces may not be necessary for the oocyst detection. The study
      highlights the occurrence of Cryptosporidium in AIDs patients of South India.

PMID- 9282527
TI  - Domiciliary health counselling in patients with sexually transmitted diseases.
AB  - To improve treatment compliance, follow-up and attendance of STD patients and
      their contacts, a programme, based on domiciliary visits was attempted. The
      programme was limited to male defaulters not responding to written and telephone
      calls. House visits to 79 out of 169 defaulters were made. Approximately half the
      number of houses were found locked. Fourteen defaulting patients reported for
      completion of their treatment and follow-up. Of these 11 were directly
      interviewed. None of the 14 patients agreed to disclose the addresses of their
      extramarital partners. During the study period 51 female sex contacts reported
      for treatment as compared to 27 in the control group. Though the numbers were
      small the study revealed that direct contact with the patient yielded the best
      results. It is suggested that to make the system cost-effective the health
      workers should spend time with STD patients in the clinic to mark out the correct
      location and time for meeting the patient either in the work place or at home in
      case of a follow-up.

PMID- 9282528
TI  - Validity of using slide positivity rate (SPR) in identification of high risk
      malarious segments in rural areas.
AB  - The Expert Committee Report-1995, recommended various parameters for identifying
      worst malaria affected segments in rural areas, which are mainly based on slide
      positivity rate (SPR). A analysis of the epidemiological data of Uttar Pradesh
      was carried out in different settings to study the sensitivity of SPR in
      identifying high risk areas. The validity of using SPR in the entire range in all
      settings is examined and appropriate corrective measures suggested.

PMID- 9282529
TI  - Measles vaccine efficacy in India: a review.
AB  - Different workers have used different designs to assess effectiveness of live,
      further attenuated measles vaccine i.e., seroconversion studies, outbreak
      investigations, field trials and coverage survey methods. The results were often
      contradictory. We reanalyzed data from these studies to find out optimum vaccine
      efficacy (VE) and its determinants in the Indian context. Although nutritional
      status and sex of the subjects did not affect seroconversion rates, the rates
      were greater among initially seronegative and older children. Overall
      seroconversion rates in 9-11 months children ranged between 56 and 96%. Studies
      showing poor seroconversion had an inadequate sample size and/or technical flaws
      that detracted from the reliability of results. However, appropriately designed
      studies demonstrated seroconversion rates of more than 90% in 9-11 months
      children who were initially seronegative. Since 5-10% of 9-11 months old infants
      had persistent measles maternal antibody, measles vaccine may be around 85-90%
      effective in this age group. These results are in agreement with the findings
      observed in outbreak investigations. These outbreaks fulfilled all the criteria
      which are considered necessary for optimum estimation of VE in such settings; VE
      was found to be more than 90% in outbreak settings. Conversely, retrospective
      coverage surveys grossly under estimated VE (about 60%) which was probably due to
      misclassification of vaccination status of enrolled children. The surveys were
      undertaken in areas where immunization records were grossly incomplete and only
      few mothers retained immunization cards. Unfortunately, VE was also under
      estimated in field trials which were neither randomized nor blind, and no placebo
      injections were used in control children; many observations were on record which
      could explain the under estimation of VE. Reanalysis of data from different types
      of studies indicates that efficacy of measles vaccine given at 9-11 months of age
      is of the order of 85-90% in the Indian context.

PMID- 9282530
TI  - Optic neuroretinitis, a rare manifestation of herpes zoster ophthalmicus: a case
      report.

PMID- 9282531
TI  - Comparison of parasitological and serological data in evaluating malaria.

PMID- 9282532
TI  - Incidence of cryptosporidiosis in children with acute and persistent diarrhoea in
      and around Shimla.

PMID- 9282533
TI  - Outbreak and control of dengue in a village in Dharmapuri, Tamil Nadu.

PMID- 9282535
TI  - Joining education and service in exploring discharge needs.
AB  - Continuity of care beyond the walls of the acute hospital setting has always been
      a major emphasis in nursing. There is concern that the care needs of older adults
      at the time of discharge have been increased by shortened hospital stays. Yet
      little is known about the specific and changing health care needs of older adults
      during the early days at home following discharge from acute care, particularly
      those who are discharged without community referrals. To learn more about the
      experiences of this population, the College of Nursing at the University of
      Southern Maine, in collaboration with the Nursing Service Department at Maine
      Medical Center, conducted a demonstration project. This project involved follow
      up home visits to older adults who were discharged to their homes from an acute
      care setting.

PMID- 9282534
TI  - The emerging recognition of cryptosporidium as a health hazard.
AB  - Cryptosporidium is the leading cause of waterborne disease in the United States.
      Cryptosporidiosis occurs as a result of this pathogen and is potentially fatal to
      the immunosuppressed population. Current water treatment standards will not
      eradicate the pathogen, resulting in a potential public health hazard. Congress
      recently passed legislation addressing cryptosporidium, and health policies are
      pending approval with strong support from the Centers for Disease Control. The
      implication for community health nursing is that nurses should take on expanded
      roles as social, political, and economic advocates and educators to support
      community actions to eradicate this pathogen.

PMID- 9282536
TI  - Family planning experiences of Vietnamese women.
AB  - The increasing Vietnamese population in the United States and the high fertility
      rate seen in this group warrant studies about Vietnamese cultural beliefs. The
      purpose of this qualitative study was to examine sociocultural factors that
      influence family planning practices of Vietnamese refugee women. Findings reveal
      that the stresses associated with starting over in a new land, such as concern
      about finances and learning English, influenced younger Vietnamese women in this
      study to use family planning methods that would limit the number of future
      pregnancies. The meaning of children and the importance of their educational
      future were also influential in determining the number of children desired and
      family planning practices. Cultural and religious beliefs also directed the
      women's choice of method. Results from this study can be used to educate health
      care professionals, increase appropriate educational material for Vietnamese
      women, and assist in the development of appropriate family planning programs.

PMID- 9282537
TI  - Prenatal care for low-income women and the health belief model: a new beginning.
AB  - Low-income women are among those at risk for delivering low-birth-weight babies
      (Lia-Hoagberg et al., 1990; Miller, Magolis, Schwethelm, & Smith, 1989; St.
      Clair, Smeriglio, Alexander, Connell, & Niebyl, 1990). These women tend to use
      prenatal care less often, perceive more barriers to care, have less positive
      reinforcement for receiving care, have less access to care, have lower education
      levels, maintain less healthy lifestyles, and have lower compliance with
      recommendations (Henderson, 1994; Koska, 1990; Lia-Hoagberg et al., 1990; Miller
      et al., 1989). This article will highlight three attributes of the problem of low
      income women and prenatal care. First, low-income pregnant women are at risk for
      delivering low-birth-weight and preterm babies, which usually leads to expensive
      subsequent care. Second, an unhealthy maternal lifestyle increases the risk of
      delivering a low-birth-weight or preterm baby. Third, there are social,
      programming, and lifestyle barriers that low-income women face in receiving
      prenatal care. Finally, this article examines the use of the Health Belief Model
      as a theoretical basis for future prenatal care programming for low-income women.

PMID- 9282538
TI  - Insomnia, alcohol, and over-the-counter drug use in old-old urban women.
AB  - Insomnia is a common complaint of older adults. Historically, alcohol and over
      the-counter (OTC) medications have been used as sedatives. Yet, there is a lack
      of information regarding the use of these substances by old-old urban women. A
      volunteer sample of 155 urban women over the age of 85 participated in a two-part
      structured interview to obtain data related to their health, sleep patterns, use
      of alcohol and OTC medication to improve sleep, awareness of hazards associated
      with use of these substances, and reason for seeking health care for insomnia.
      Findings indicate that all of the women had health problems and difficulty in
      sleeping. The majority used alcohol, OTC medication, or both on a regular basis
      in an effort to improve their sleep. Nurses who work with very old women need to
      assess clients' use of these substances and the side effects associated with
      them.

PMID- 9282539
TI  - Infant feeding practices of low-income African American women in a central city
      community.
AB  - It is a well-established fact that nutrition is central to the growth and
      development of all infants. Yet it has been observed that health care
      professionals are frequently unfamiliar with the most typical infant feeding
      practices of the clients within the communities they attempt to serve. This
      observation was apparent during the development of a program in an inner-city
      community of Wisconsin to support the feeding practices of low-income African
      American women with low-birth-weight infants. As a result of initial encounters
      with prospective clients and health care and social service professionals from
      the targeted community, it was apparent that professionals and staff involved in
      this project needed to gain an understanding of common infant feeding practices
      of low-income African American women; a greater awareness of the values, beliefs,
      and health care practices of the population; and a greater understanding of the
      impact of poverty on the families within the targeted community. To assist the
      staff in gaining a better understanding of the influence of culture and economics
      on infant feeding practices, a study of the infant feeding practices of a select
      group of low-income African American women was undertaken. The study aimed to (a)
      gather information that could be used to describe common infant feeding practices
      of low-income African American women in an inner-city community of Wisconsin and
      (b) determine the influence of cultural and economic variables on the decisions
      made by low-income African American women regarding infant feeding. This article
      presents an analysis and summary of the data collected during the course of the
      study.

PMID- 9282540
TI  - Maximal sweating rate in humans.
AB  - We reviewed the literature concerning the maximal sweating rate (SRmax) during
      heat acclimatization, walking in desert heat and marathon running, and analyzed
      it from the viewpoint of sex, age, level of maximal oxygen uptake, and
      experimental conditions, i.e., ambient temperature, relative humidity, work
      intensity, work type, working duration, seasonal factors and the techniques of
      heat acclimatization. Exercise simulation, walking, running or bicycling, to
      induce the SRmax was conducted in a hot climatic chamber or in the desert. The
      SRmaxs due to marathon running were 1,000 to 1,200 g.h-1 in the cold season and
      1,500 to 2,000 g.h-1 in the hot season. After several days of heat
      acclimatization, sweating capacity in the exercise simulation reached a maximum
      rate, over 2,000 g.h-1. There was a sexual difference in the SRmax, and the
      sweating capacity in the female was less than that in the male. Thus, the maximal
      sweating capacity in human was observed by prolonged moderate muscular exercise
      under thermal stress and internal and/or external heat loads.

PMID- 9282541
TI  - Neurobehavioural changes in workshop painters of a public transport network.
AB  - To determine alterations in functional capacities due to exposure to solvents in
      painters, a battery of psychological tests consisting of associative recall,
      critical flicker fusion, letter cancellation, Muller-Lyer illusion and card
      sorting was administered before their work day schedule starting at 0800 h, 16 h
      after cessation of their work the previous day. Simultaneously a reference group
      of diesel worker and a control group were also tested at the same time of day.
      Age-adjusted performance scores were calculated for the painter group and diesel
      worker group based on the linear age trend of the control group. Analysis of
      variance suggested significant degradation in performance on tests of critical
      flicker fusion (alternate), letter cancellation, Muller-Lyer illusion and card
      sorting (by design configuration). Persistence of solvent exposure effects
      through visual and motor function impairments is reflected.

PMID- 9282543
TI  - Characteristics of Roman character input in Japanese word processing on keystroke
      interval time.
AB  - This study clarifies the characteristics of the time keys that are taken to enter
      Roman letters for Japanese sentences. First, test the appearance frequency of two
      consecutive characters of the alphabet in the input of English sentences and in
      the input of the Roman characters of Japanese sentences. Based on these results,
      we analyzed the features of stroke frequency of the keys in the Roman character
      input. Based on the result of the analysis, we clarified the features of the
      keystroke interval time for two consecutive characters in the Roman character
      input. Then, keys were struck to enter Japanese sentences for a fixed period of
      time and a test was made for the characteristics. As a result, the following
      points were clarified: 1) The time keys struck were divided into two large
      groups. One for two consecutive alphabet letters that corresponded to Kana, or
      the Japanese syllabary, and the other with no correspondence. The former had
      smaller values for the mean time and deviations, and the latter had larger values
      for them. 2) The subjects who struck a larger number of keys per unit time took
      less time in typing two consecutive letters which did not correspond to Kana.

PMID- 9282542
TI  - Physical workload during selected farm operations.
AB  - An investigation was conducted to determine the physical workload on agricultural
      workers during selected farm operations in paddy fields in Thailand. Four male
      and four female agricultural workers were randomly selected. Four common farm
      operations, i.e. ploughing, planting, weeding and harvesting, were selected. The
      physical responses in terms of heart rate, oxygen consumption and pulmonary
      ventilation were determined as a function of physical work capacity on a
      laboratory bicycle ergometer. During different field operations, heart rate,
      oxygen consumption and pulmonary ventilation were recorded and energy
      expenditure, oxygen pulse and relative cost were estimated. The postural
      discomfort was also assessed during different farm operations. It was observed
      that the physical workload for ploughing, planting, wedding and harvesting
      operations, expressed in percent of physical work capacity, was 44, 41, 33 and
      44%, respectively. Ploughing was found to be the heaviest work and other
      operations were moderate. Postural discomfort was higher for ploughing than for
      other operations.

PMID- 9282544
TI  - Comparative study on the muscular load of the arms using hair driers.
AB  - The purpose of the present study was to evaluate the muscular load of the arm
      when combing the hair using different "kuru-kuru" type of hair driers. Ten female
      students (20-24 years old) volunteered as subjects. Five combing patterns were
      conducted as follows: 1) comb outer layer of right side of hair using right hand,
      2) comb outer layer of left side of hair using right hand, 3) comb inner layer of
      left side of hair using right hand, 4) comb outer layer of back hair using right
      hand, and 5) comb inner layer of right side of hair using left hand. Surface EMGs
      were recorded from M. flexor carpi ulnaris, M. brachioradialis, M. biceps
      brachii, M. triceps brachii, M. deltoideus and M. trapezius of both sides of
      body. Integrated EMGs (iEMGs) were used to evaluate muscular load for each of the
      seven different types of hair driers used. The relationship between iEMGs and
      weight, center of gravity, diameter, length, and circumference of each hair drier
      were examined. The weight of hair driers tended to be the effective factor on the
      muscular load. Muscular load also had a tendency to be affected by the shape of
      the grips. With regard to the hand size, the longer the thumb length, the smaller
      is the muscular load. It was suggested that a relatively large diameter of the
      bulb-shaped grip of the drier gave a smaller muscular load among the hair driers
      examined in the present experiment.

PMID- 9282545
TI  - Third order tooth movements with straight wire appliances. Influence of
      vestibular tooth crown morphology in the vertical plane.
AB  - 1. The labial surface in the vertical plane was investigated in 3 sections:
      center, mesial, and distal edge of an ideally positioned bracket. The material
      consisted of 28 casts taken from 14 female and male individuals with a mean age
      of 26.8 years. 2. After trimming each cast, the resulting surface was
      photocopied, enlarged 8 times, then digitized under a 2.0 mm grid (corresponding
      to 0.25 mm of the original size). 3. Using a statistical computer program, mean
      curves including standard deviations and non-linear regression curves were
      calculated from the individual data. In accordance with their anatomy 3 groups of
      teeth were formed in each jaw: front teeth, premolars, and molars. The curves,
      including the comparison of the squared regression curves, provide an accurate
      mathematical description of the labial tooth crown in the above-stated sections.
      4. The angle differentials between a reference tangent and 20 other tangents were
      calculated. From a practical standpoint, information is obtained on the extent to
      which the torque of a tooth would be changed if a bracket was to be positioned
      vertically (in 0.5 mm increments) from its ideal position. These changes of
      torque fluctuate on average between 1.3 degrees (mandibular front teeth) and 3.3
      degrees (mandibular molars) for every 0.5 mm of vertical deviation. 5. The
      calculated comparisons of the curves permitted the construction of bracket bases
      filling-at least in the vertical dimension-the tooth surface most accurately in
      the "optimal" position.

PMID- 9282546
TI  - Continuous arch wire technique using the bending art system.
AB  - The bending art system (BAS) enables computerized production of individual arch
      wires for the multiband technique. Treatment planning using the continuous arch
      technique as part of the bending art system has been described. Planning of the
      arch wires follows an initial camera picture taken in the patient's mouth, and is
      divided into the following steps: ideal arch, target arch and course of
      treatment. The ideal arch establishes the individual shape of the arch wires in
      the horizontal plane. Based on the input of various small adjustments, the ideal
      arch is transformed into the target arch which represents the final arch of the
      treatment. Finally, the sequence of the various arches is established. The
      geometry of the intermediate arches is calculated on the assumption that each
      tooth is moved the shortest possible distance during transformation from the
      initial arch to the target arch. This procedure, called the direct method, is
      compared with the newly developed indirect method. With the indirect method, the
      camera picture is taken of the initial cast and the target arch is produced in
      accordance with a setup model in ideal occlusion. In contrast to the straight
      wire technique, treatment with the BAS is not finalized with a straight arch wire
      since the occlusion of the individual patient rarely complies with the straight
      wire norm.

PMID- 9282548
TI  - Premolar child-to-parent grafting within the framework of orthodontic serial
      extraction.
AB  - While allografting of human teeth holds all the risks and problems of
      immunological reactions or host-versus-graft reactions encountered in any organ
      transplantation, root resorption and thus the loss of the grafted tooth may be
      delayed by several decades if the transfer is between close relatives and minimum
      histocompatibility is 50%. In 2 cases premolars with incomplete root growth,
      which had to be extracted because of considerable crowding, were transplanted
      from child to mother and child to father, respectively. The grafts healed without
      complications and after a retention time of several weeks the teeth were
      attached. Three years after transplantation the teeth show only minor signs of
      root resorption and are fully functional.

PMID- 9282547
TI  - Antimicrobial effect of a chlorhexidine-thymol varnish (Cervitec) in orthodontic
      patients. A prospective, randomized clinical trial.
AB  - The aim of the present investigation was to study the effect of combined
      application of a fluoride varnish (Fluor Protector) and an antimicrobial varnish
      (Cervitec) on the oral microflora, caries and gingival condition in patients
      receiving treatment with fixed orthodontic appliances. A total of 198 individuals
      (12 to 15 years old), scheduled for fixed orthodontic treatment, were randomized
      into 2 groups. Prior to bonding, the Cervitec and the control group received one
      application with Cervitec or a placebo every week for 3 weeks, respectively. In
      the Cervitec group. Fluor Protector was applied at bonding and Cervitec at the
      next visit, 6 weeks later. Each varnish was then applied every 12 weeks for 24
      weeks. In the control group, the fluoride varnish was applied only at bonding and
      every 12 weeks. The Visible Plaque Index (VPI), the Gingival Bleeding Index
      (GBI), the White Spot Lesion Index (WSL) and the level of mutans streptococci in
      plaque and saliva were recorded 3 weeks prior to bonding and after 24 weeks. At
      bonding and after 12 weeks, only VPI, GPI, plaque and salivary mutans
      streptococcus counts were recorded. During the 3-week prebonding period, the mean
      VPI, GBI and mutans streptococci in plaque decreased in both groups. At bonding,
      the mean level of mutans streptococci in plaque was significantly lower in the
      Cervitec group than in the control group. The mean level of mutans streptococci
      was significantly lower after 12 weeks' bonding in the Cervitec group than in the
      control group. No effects on the other parameters were found during the 24 weeks.

PMID- 9282549
TI  - Dentistry and speech production. Correlations between the morphology of the
      articulation zone and acoustics exemplified in /s/ articulation.
AB  - Many factors are thought to be responsible for misarticulation. Maxillomandibular
      or dental irregularities play an important role as one of these factors.
      Correlations between morphological changes in dental status and speech disorders
      are well known, but different opinions are discussed in the literature. A
      reciprocal relationship between dysfunction and various dental irregularities is
      assumed. The objective of our review and experimental investigations was to
      document the influence of dental irregularities on speech articulation as
      exemplified by the second articulation zone and /s/ articulation. The second
      articulation zone was experimentally changed by application of dental cement to
      the palatal surface of the upper incisors. Various words were spoken before and
      just after the change to the frontal teeth. The /s/ articulations were
      acoustically analyzed by means of sonography and compared with each other.
      Although this modification of the teeth, which was identical in all probands,
      leads to /s/ misarticulation from the standpoint of auditory analysis,
      interindividual differences were recorded by acoustic means. It is thus possible
      to differentiate objectively between acoustically correct and incorrect /s/
      articulation. Speech and articulation are, however, such complex mechanisms that
      it is impossible to characterize them by simple causal connections with
      maxillomandibular or dental irregularities.

PMID- 9282551
TI  - Subacute hepatic failure--unresolved issues?

PMID- 9282550
TI  - Combined intrusion and retraction generated by cantilevers with helical coils.
AB  - Combined retraction and intrusion of the anterior teeth is often needed as part
      of orthodontic treatment. The use of a statically determinate force system has
      many advantages over statically indeterminate systems. In the case of the
      cantilevers the orthodontist can evaluate the line of action of the delivered
      force directly in the clinical situation. In the present paper the force system
      delivered by stainless steel and beta titanium cantilevers with an eccentrically
      placed helix was evaluated. The cantilever consisted of a straight piece of wire
      bent to form a helix with an external diameter of 3 mm. The wire was fixed into a
      bracket of sensor 1, touching sensor 2 of a test bench with a 1-point contact to.
      Activation was induced by rotating sensor 1 into which the wire was tightly
      fixed. This was done in 2 different modes, one in the direction in which the
      helix was bent and one in the opposite direction. With an interval of 5 degrees
      the force system generated with respect to sensor 1 and the direction of the
      force delivered to sensor 2 (the other bracket) were registered. The results were
      expressed graphically and the influence of material and activation mode were
      evaluated statistically by comparing the coefficient of regression. As expected,
      the influence of the material reflected the relative stiffness of the 2 alloys.
      As TMA is monocrystalline (i.e. consists of homogeneous crystals) the mode of
      activation did not reflect any significant Bauschinger effect as seen in the case
      of stainless steel. Analysis of the force direction confirmed that the suggested
      wire configuration is useful for delivery of a predetermined combination of
      horizontal and vertical force. This was confirmed by a finite element analysis.

PMID- 9282552
TI  - Sepsis.

PMID- 9282553
TI  - Clinicopathological profile of subacute hepatic failure.
AB  - Twenty two patients of subacute hepatic failure (SAHF), diagnosed when jaundice
      progressed for more than 8 weeks with appearance of ascites, with or without
      encephalopathy, along with biochemical evidence of hepatocellular damage, were
      studied. The male and female ratio was 4.5:1 and majority (45.4%) of cases were
      between the age group of 41-50. The mean biochemical values were: S.bilirubin;
      9.2 +/- 3.8 mg/dl SGOT; 94.4 +/- 25.0 I.U./lit., SGPT; 107.8 +/- 32.7 I.U./lit.,
      S.Protein; 5.2 +/- 3.5 secs. Ascitic fluid analysis showed transudate in 16
      (72.7%) and exudate in 6 (27.2%) patients. Bacterial peritonitis was found in 5
      (22.7%) patients. Liver biopsy showed bridging and submassive necrosis. The
      complications developed in the hospital were: renal failure (36.3%), infection
      (27.2%), G.I. bleeding (18.1%) and encephalopathy (13.6%). The mortality was
      (86.3%). Out of 3 (13.6%) patients who survived, only two recovered completely
      and one had biochemical evidence of hepatocellular necrosis after 6 months of
      follow up.

PMID- 9282555
TI  - Intercostal tube drainage of pleura: urosac as chest drainage bag.
AB  - Chest drainage bags are an alternative to underwater seal drainage. Urosac
      functions on the same principles and therefore can be used as a cheap and easily
      available substitute. 40 patients requiring intercostal tube drainage (ICD) were
      included in the study. 29 pneumothoraces and 11 pleural effusions of various
      etiologies were treated with intercostal drain attached to urosac bag. The period
      of ICD ranged from 4 days to 106 days. 2 patients were treated at home for
      prolonged periods without any complications. Urosac used as a chest drainage bag
      is safe and effective and can be used as an alternative to underwater seal
      drainage with several advantages.

PMID- 9282554
TI  - Balloon dilatation of inferior vena cava stenosis in Budd-Chiari syndrome.
AB  - Percutaneous balloon angioplasty was used to dilate inferior vena cava (IVC)
      stenosis in 12 patients with Budd Chiari syndrome. There were seven men and five
      women, aged 32.8 +/- 8.5 years. Angioplasty was performed using balloon 18-20 mm
      in diameter. In eleven (91.6%) patients, IVC could be successfully dilated. In
      these eleven patients, the caval diameter at the site of stenosis increased from
      2.3 +/- 1.5 to 13.1 +/- 2.8 mm (p < 0.001), the mean IVC pressure decreased from
      28.2 +/- 4.1 to 10.5 +/- 3.4 mmHg (p < 0.001) and the gradient across the
      stenosis decreased from 23.1 +/- 2.2 to 4.2 +/- 1.9 mmHg (p < 0.001). There was
      appreciable clinical improvement after angioplasty. On a mean followup of 10.8 (3
      18) months four (36.4%) patients had restenosis which could be successfully
      dilated again. These results suggest that balloon dilatation of inferior vena
      cava stenosis is safe and effective, however, recurrence is common and needs
      redilatation.

PMID- 9282556
TI  - Clinical and etiological profile of ataxic hemiparesis.
AB  - We studied the clinical profile and etiology of 28 cases of ataxic hemiparesis.
      After a detailed neurological examination, CT scan brain (plain and after IV
      contrast) was done in all. Age ranged from 18 to 80 years. Acute onset of
      symptoms was in 22, while 6 had insidious onset. 18 patients had major infarct,
      while 4 patients had lacunar infarct. 2 patients were found to have haematoma (1
      following head injury) and 1 each had tuberculoma, meningioma, glioma and
      toxoplasma granuloma. The lesions were seen in various parts of brain stem,
      thalamus, basal ganglion, internal capsule and frontal, parietal and temporal
      region. Heterogeneity as regards to etiology and localisation is being
      highlighted.

PMID- 9282557
TI  - Correlation of rainfall with upsurge of malaria in Rajasthan.
AB  - There has been a recent increase in malaria cases in Rajasthan. To determine
      whether environmental factors such as rainfall explain the upsurge we performed a
      study correlating the amount and duration of rainfall with annual malaria
      incidence. Data of annual incidence of malaria and Plasmodium falciparum malaria,
      annual and monthly rainfall and cultivated land area in Rajasthan were acquired
      from government sources from 1980 to 1994. The mean annual malaria incidence was
      277 +/- 90 cases/100,000 population and falciparum malaria 70 +/- 43
      cases/100,000 population per year. There was rising trend in total malaria and
      specially falciparum malaria incidence (r = 0.50, p = 0.057) over these years.
      The mean annual rainfall in the state was 541 +/- 144 mm/year and the mean
      cultivated land area was 15.5 +/- 1.2 million hectares/year with a significant
      interrelationship (r = 0.66, p = 0.008). The overall malaria incidence showed a
      moderate correlation (r = 0.48, p = 0.069) with annual rainfall while the
      incidence of falciparum malaria showed a significant correlation (r = 0.61, p =
      0.016). Rainfall in the months of June, July and August did not show any
      significant correlation with annual malaria incidence. Rainfall in the month of
      September showed significant correlation with the incidence of overall malaria (r
      = 0.62, p = 0.015) as well as falciparum malaria (r = 0.71, p = 0.003). This
      relationship remained significant after adjustment for years of study and
      cultivated land-area (standardised regression coefficients: total malaria (b =
      0.72, p = 0.060), falciparum malaria (b = 0.64, p = 0.059). There is a positive
      correlation of rainfall with incidence of malaria. Prolonged rains as suggested
      by rainfall extending to the month of September are associated with significantly
      higher incidence of total as well as falciparum malaria.

PMID- 9282558
TI  - Heart in hypothyroidism--an echocardiographic study.
AB  - 55 individuals, 44 of whom served as patients and 11 as controls were included in
      this study. Patient group was further divided into overt and subclinical
      hypothyroid group each having 22 patients. Patients were examined in a
      prospective manner and results compared with control group with an aim to
      evaluate the effect of hypothyroidism subclinical and overt on cardiac status by
      echocardiography. Variables of heart structure and function were assessed by
      cross sectional and Doppler echocardiography. IVS dimensions were significantly
      raised in moderate subclinical and in severe overt hypothyroidism (mean 0.911 +/-
      0.038 and 0.973 +/- 0.217 cm). LVPW thickness was significantly increased only in
      overt hypothyroidism (mean 1.378 +/- 0.246). However RVW and LVID showed no
      definite pattern of change. Pericardial effusion and Diastolic dysfunction was
      seen in significant cases only in overt hypothyroidism. To conclude,
      hypothyroidism both subclinical and overt is associated with cardiovascular
      alteration both structural and functional. IVS and LVPW thickness are markedly
      affected, as well as there is impairment of left ventricular function more in
      diastole.

PMID- 9282559
TI  - Video--EEG monitoring in intractable attacks of uncertain etiology.
AB  - Video-EEG monitoring was done in 26 patients with paroxysmal intractable attacks
      of uncertain etiology to determine the nature and cause. Two broad categories
      were identified: Those with prominent motor activity and those with attacks of
      collapse/limpness. Events were recorded in 16 patients of which 11 showed no
      abnormality on the simultaneously recorded EEG, thus helping to confirm their
      diagnosis of pseudoseizures.

PMID- 9282560
TI  - Audiovisual aids: guidelines for the use of overhead projector.
AB  - The overhead projector is a versatile audio-visual (AV) aid. When used
      effectively, it can render a presentation very impressive. It is easy to maintain
      and operate, and offers considerable flexibility of text and image projection. It
      is the most commonly used AV aid in teaching institutions and an appreciation of
      its strengths and weaknesses can be useful to teachers and students alike.

PMID- 9282561
TI  - Intraventricular conduction disturbances.

PMID- 9282562
TI  - Septic shock: pathogenesis and treatment.

PMID- 9282563
TI  - Mediastinal dermoid presenting as extrapleural sign.

PMID- 9282565
TI  - Sinus histiocytosis with massive lymphadenopathy.

PMID- 9282564
TI  - Myocardial contusion.

PMID- 9282566
TI  - Pneumomediastinum--a clinical dilemma.

PMID- 9282567
TI  - Magnetic resonance imaging findings in a patient with sporadic motor neuron
      disease.

PMID- 9282568
TI  - Spontaneous medullary haemorrhage due to occult vascular malformations.

PMID- 9282569
TI  - Myocarditis in herpes zoster.

PMID- 9282570
TI  - Do corticosteroids influence the disease course or mortality of Guillain Barre
      syndrome?

PMID- 9282571
TI  - Adrenal insufficiency in India.

PMID- 9282572
TI  - Carbamazepine induced sino-atrial block in a young adult.

PMID- 9282573
TI  - A rare presentation of falciparum malaria.

PMID- 9282574
TI  - Platelet adrenoceptors in health and disease.

PMID- 9282575
TI  - Extrahepatic uptake on isotope liver-spleen scan: what it means and what it does
      not.

PMID- 9282576
TI  - Studies on the platelet alpha-adrenoceptor subtypes in diabetes mellitus.
AB  - Studies on the platelet alpha-adrenoceptor subtypes were carried out in 19
      subjects with treated diabetes mellitus and 15 normal age and sex-matched
      controls. By utilising selective antagonists, it was noted that all the normal
      human platelets exhibited the alpha-2 adrenoceptor. 7 diabetics (37%) expressed
      both the alpha-1 and alpha-2 adrenoceptors and diabetic complications along with
      hypertension were most common in this group. Another 7 diabetics (37%) expressed
      the alpha-2 receptor only and diabetic complications were minimum in this group.
      Interestingly, 5 diabetics (26%) did not express either the alpha-1 or alpha-2
      receptor and these patients occupied an intermediate position with regard to
      diabetic complications. Thus, it was concluded that platelet alpha-1
      adrenoceptors perhaps indicated a poor prognosis in diabetes mellitus, opening up
      future scope for work in this area.

PMID- 9282577
TI  - Significance of radioisotope bone marrow uptake on 99m technetium sulphocolloid
      scan in portal hypertension.
AB  - A prospective study of 101 consecutive patients of portal hypertension was
      carried out to study the possible relationships between bone marrow activity on
      99m technetium labelled sulphocolloid scan and severity of liver disease,
      etiology of portal hypertension and cirrhosis, as well as presence and extent of
      collateral circulation, including esophageal varices. The patients were divided
      into 4 etiological groups: alcoholic cirrhosis (ALD), (38) non-alcoholic
      cirrhosis (NALD) (35) non-cirrhotic portal fibrosis (NCPF) (14) and extrahepatic
      portal vein obstruction (EHPVO) (14). Patients of cirrhosis were categorised
      according to modified Child-Pugh's classification. Esophageal varices were graded
      endoscopically as (1) no varix (2) small varices (< 5mm) (3) large varices (>
      5mm). All patients underwent radionuclide imaging using 99m Technetium labelled
      sulphocolloid and bone marrow activity was studied. Evaluation of portasystemic
      collaterals was done ultrasonically. We found that 16.6%, 44.6% and 72.72%
      patients with Child A, B and C cirrhosis respectively, had increased marrow
      activity (p < 0.05). There was no significant difference between marrow activity
      of patients with ALD (52.6%) and NALD (40%). None of the non-cirrhotic patients
      demonstrated bone marrow uptake of radioisotope. There was no significant
      difference between bone marrow uptake presence of lienorenal collaterals and
      presence or size of esophageal varices. We thus conclude the bone marrow activity
      on radioisotope scanning depends only on the severity of liver disease and does
      not vary a according to the etiology of cirrhosis, or presence and extent of
      portasystemic collaterals, including esophageal varices.

PMID- 9282578
TI  - Complications of treadmill testing.
AB  - Complications occurring in 2,400 treadmill tests are reported, out of which 2107
      (87.8%) were on males and 292 (12.2%) on females. The total number of patients
      with complications was 29 (1.2%) and the types were: acute MI in 2, ventricular
      tachycardia (sustained) in 3, nonsustained in 7 with ventricular couplets in 3
      patients, atrial tachyarrhythmias in four of AVNRT in 2, EAT in 2, SVT with
      abberancy in 1, SVT (undifferentiated) in 3, bradyarrhythmias in form of sinus
      bradycardia in 4, hypotension in 4 and AV block in 2. There were no deaths. Only
      8 (0.33%) patients required treatment-2 each of acute MI, sustained VT, AVNRT and
      hypotension, though only 4 of them were hospitalised (2 each of acute MI and VT)
      and subsequently discharged. Highest incidence of complications was seen in post
      MI patients (2.01%) followed by those with typical anginal pain (1.9%) and they
      had more serious problems in form of MI and sustained VT. 55.17% patients with
      complications were positive for provocative ischaemia as compared to 22.75%
      positivity in the total. Although 14 (38.2%) patients developed complications at
      workload of 4-6 METS but 2 achieved load of 10 METS also. Complications were seen
      mostly during exercise and also during recovery only.

PMID- 9282579
TI  - "Orthoryhthmia" or postural cardiac dysrhythmia: clinical significance.
AB  - The objective of present paper is to present results of preliminary observations
      and studies carried out in fifty individuals developing cardiac dysrhythmia on
      assuming a supine posture. Detailed history taking, clinical examination, and
      study of metabolic parameters were carried out. Blood pressure, ECGs and rhythm
      strips were recorded in supine and upright postures, after exercise and DMT,
      after i.v. injection of atropine and after oral administration of probanthine.
      Majority of the individuals studied were asymptomatic. Palpitation was the
      commonest symptom. Bradycardia was observed in all as well as a low blood
      pressure. Supraventricular ectopic rhythm was the commonest dysrhythmia observed.
      Arythmia appeared on assuming a supine posture and tended to disappear in upright
      position and after exercise. I.v. atropine had a similar effect in a majority of
      cases, oral probanthine was not very effective. These observations highlight the
      existence of a hitherto unreported effect of posture on cardiac rhythm. This
      phenomenon appears to be a benign condition and can be termed as "orthorhythmia".

PMID- 9282580
TI  - Normal spirometry in healthy natives of Bhutan.
AB  - We performed spirometry on 333 healthy Bhutanese men and women at Thimpu.
      Prediction equations were derived using age and height as regression
      coefficients. Age had a significant negative correlation while both height and
      weight had positive linear correlation with spirometric indices. The relationship
      of weight with FVC was explained largely on the basis of the "muscularity" effect
      of weight. Bhutanese have lower ventilatory parameters than the Europeans and the
      North Indians. The difference is likely to be ethnic in origin.

PMID- 9282581
TI  - Effect of enalapril on renal profile and right ventricular dimensions in chronic
      cor pulmonale.
AB  - The effect of enalapril in combination with bronchodilators, diuretics,
      antibiotics and/or steroids, was compared with that of conventional treatment
      with diuretics, steroids and antibiotics alone in 30 patients of chronic cor
      pulmonale. The effect was studied on right ventricular dimensions and renal
      profile after a period of 6 weeks treatment. The control patients showed a
      significant decrease of RVIDED and increase in GFR, but the decrease of RVAWT and
      increase of 'a' wave amplitude was insignificant. However when the ACE-inhibitor
      enalapril was added to the treatment, there was a significant decrease of RVIDED,
      RVAWT and an increase of 'a' wave amplitude with a significant improvement in the
      GFR. A comparison between both the groups showed that the increase of GFR and
      decrease of RVIDED was higher in enalapril group than controls. The increase of
      'a' wave amplitude was also greater in enalapril group. Thus enalapril appears to
      be of value in chronic cor-pulmonale, where it decreases pulmonary hypertension
      and thus right ventricular after load. It also decreases renal vascular
      resistance increasing the renal blood flow, thus improving the GFR.

PMID- 9282582
TI  - Newer bacterial pathogens in relation to acute diarrhoeal diseases--an overview.

PMID- 9282584
TI  - Infectious agents and immunological disturbances in relation to chronic fatigue
      syndrome.

PMID- 9282583
TI  - Ramadan fasting--effects on health and disease.

PMID- 9282585
TI  - Cryptococcemia and meningococcemia in a post partum woman.

PMID- 9282586
TI  - Idiopathic dilatation of pulmonary artery.

PMID- 9282588
TI  - Primary systemic amyloidosis--pleural involvement with exudative pleural
      effusion.

PMID- 9282587
TI  - Pyrethroid poisoning.

PMID- 9282589
TI  - Epidermolysis bullosa with esophageal web.

PMID- 9282590
TI  - Disseminated cryptococcosis.

PMID- 9282591
TI  - Early post myocardial infarction pericarditis with delayed resolution.

PMID- 9282592
TI  - Progressive systemic sclerosis with breast cancer.

PMID- 9282593
TI  - Destructive bone lesion in primary amyloidosis.

PMID- 9282594
TI  - Priapism--a rare presentation in chronic myeloid leukaemia.

PMID- 9282595
TI  - Chicken pox with cranial nerve palsy.

PMID- 9282596
TI  - Magnesium replacement in obstructive airway disease.

PMID- 9282597
TI  - Prevalence of HIV infection among renal transplant patients in Madras/India.

PMID- 9282598
TI  - Thrombocytopenia--a rare but serious side effect of rifampicin.

PMID- 9282600
TI  - Mechanics and cardiology.

PMID- 9282599
TI  - More uses of drugs.

PMID- 9282601
TI  - Unusual complications of malaria.

PMID- 9282602
TI  - AIDS in the ICU.

PMID- 9282604
TI  - HIV in intensive care--a 3 years experience.
AB  - A three year prospective study of a total of 62 critically ill HIV patients in
      MICU showed a rising percentage from 0.86 in 1992 to 3.17 in 1994. Four major
      presentations were observed, neurological-20 patients (32.5%), sepsis syndrome-18
      (29%), poisoning-10 (16.1%) and miscellaneous-14 (22.6%). Acute poisoning emerged
      as the most important preventable indication for MICU admissions. Interventions
      like CVP and haemodynamic monitoring-25 patients, endotracheal intubation-18,
      mechanical ventilation-14, tracheostomy-3, haemodialysis-3 were done when
      indicated. The mortality of the 14 ventilated patients was high at 92.9% compared
      to the overall HIV mortality of 46.8%. This study shows that critically ill HIV
      patients do deserve intensive care management with optimum infection control
      precautions. Survival of 53.2% is noteworthy in a resource stretched set up.

PMID- 9282603
TI  - Unusual acute and chronic complications of malaria.
AB  - 32 cases (21 acute severe malaria and 11 chronic malaria syndrome), who developed
      unusual complications and/or manifestations are reported. The acute
      manifestations were unexplained tachypnoea 4, pulmonary oedema 5 and shock due to
      multiple organ dysfunction syndrome 3, melena 2 and E coli septicaemia in one.
      The other features were concomitant salmonellosis 2, meningitis 1, renal failure
      3, hepatorenal syndrome 2, hepatitis like illness 7, neck stiffness with normal
      CSF 3, urticaria and subconiunctival haemorrhage 2 each, apyrexial spell with
      anaemia 4, thromocytopenia 3, and hypoglycaemia 3 (two pretreatment and one while
      on quinine in 5% glucose drip). The chronic syndrome noted were hyperreactive
      malaria syndrome (Tropical splenomegaly) 3, repeated haemolysis 2, chronic simple
      malaria with positive parasitaemia and normal Igm levels 4, and cerebellar ataxia
      with tremors 3. Bone marrow in these cases was hypercullular with increase plasma
      cells. Liver biopsy revealed lymphocytic infiltration. There was no case with
      permanent neurogical deficit. All patients with pulmonary oedema and multiple
      organ dysfunction died but chronic syndrome patients recovered fully. Early
      recoginition of atypical manifestation and prompt treatment will decrease the
      mortality and morbidity due to malaria.

PMID- 9282605
TI  - Prevalence of islet cell antibodies and B cell functional status in insulin
      dependent diabetes.
AB  - As autoimmunity is an important factor in the etiopathogenesis of IDDM, 85
      ketosis prone i.e. insulin dependent diabetes (IDD) were evaluated for
      immunological and beta cell functional status. Islet cell antibodies (ICA)
      against purified islet cells used in Microwell ELISA Method, were detected in
      27.1% of cases (23/85). There was a prevalence of 36.4% of ICA positivity in
      newly diagnosed cases and its prevalence declined with duration. The highest ICA
      positivity was observed in fourth decade of life. 17 of the 23 ICA positive cases
      (73.9%) had a mean duration of 2.1 years whereas the remaining 6/23 (26.1%) had a
      mean duration of 9 years. Females showed a younger age of onset of diabetes. Only
      one female with duration of 10 years tested positive for ICA.ICA positive males
      had later age of onset and longer duration of diabetes as compared to ICA
      positive females. Ten ICA positive cases studied were showing non-significant C
      peptide (CP) release (after glucose load) in comparison to negative cases (14); p
      < 0.05, 8 of these cases were with < 3 months duration. Significantly low delta %
      C-peptide response implies a low residual beta-cell function and further loss of
      beta cell function earlier in ICA +ve cases. Thus this study leads to understand
      in depth the immune mechanism of IDDM.

PMID- 9282606
TI  - Pattern of gall stone disease in Madras city, south India--a hospital based
      survey.
AB  - Gall stone disease profile was studied retrospectively in 346 patients between
      Aug 1986 and 1992. The mean age for men was 51.1 years and for women 46.2 years.
      Male female ratio was 1.3:1. Gall stones were statistically more common in
      nonvegetarian alcoholics. Smoking did not influence its occurrence.
      Cholecystectomy was preferred to medical treatment. Chemotherapy failed to show
      any therapeutic response. Macroscopically 77% of calculi were pigment and 17%
      mixed stones. Rest were cholesterol stones. The demographic pattern of gall stone
      disease, the morphological appearance of calculi and response to medical
      treatment differs from gall stones in North India.

PMID- 9282607
TI  - A study of inferior vena cava obstruction.
AB  - Inferior Vena Cava obstruction as a major cause of hepatic venous outflow block
      is not so common. A prospective study of 20 cases gave us an opportunity to
      device a management protocol for this disorder. Out of 20 cases we had studied,
      12 had only inferior Vena Cava obstruction while rest of the 8 cases had both
      hepatic vein and IVC blockade. However, balloon cavoplasty showed remarkable
      results with substantial clinical and haemodynamic improvement in cases with
      isolated IVC obstruction. Therefore, we suggest that patients with IVC
      obstruction should be actively managed with Vena-cavography followed by
      cavoplasty. Treatment of Hepatic venous obstruction along with IVC obstruction is
      controversial; bypass shunt is usually required and long term follow-up studies
      are required to establish safety and efficacy.

PMID- 9282608
TI  - Cervical spine involvement in rheumatoid arthritis: prevalence and relationship
      with overall disease severity.
AB  - Rheumatoid arthritis (RA) affects the cervical spine in 20-90% of patients in
      Western countries. We report the prevalence of cervical spine involvement in RA
      and its relationship with duration of disease, seropositivity, hand joint
      erosions and symptoms and signs suggestive of cervical spine involvement. 100
      patients with RA criteria were included. Apart from clinical history and
      examination, study included X-rays of the cervical spine in AP, open mouth and
      lateral views and posteroanterior view of hands and rheumatoid factor estimation.
      All X-rays were read by a radiologist who was unaware of the clinical details.
      Cervical spine involvement was seen in 65% of patients. The commonest abnormality
      was erosions of the odontoid process (47%), followed by atlanto-axial dislocation
      and apophyseal joint involvement (24%). Only 5% of patients had abnormalities of
      spinous processes or vertebral bodies. Patients with abnormal cervical spine
      radiographs had higher prevalence of rheumatoid factor and erosions on hand
      radiographs. Severity of cervical spine changes was related to duration of
      disease (> 5 years). No correlation was seen between symptoms and radiological
      abnormalities except when neurological deficit was present. Patients with
      seropositivity, erosive disease and disease duration greater than five years
      should be screened for cervical spine disease.

PMID- 9282611
TI  - The 'small spleen' in malaria.
AB  - A cardinal feature of malaria, splenomegaly, is usually absent in adult patients
      who have already suffered from falciparum malaria or who are natives of an
      endemic falciparum zone. This is an attribute of the past episode of clinical or
      sub-clinical malaria which usually results in regression of the splenic size to
      below-normal. An ultrasonographic evaluation of spleens was done in 90 healthy
      adult males, who had suffered from vivax (n = 28) or falciparum (n = 25) malaria
      in the past, except the controls (n = 22) and natives from an endemic falciparum
      area (n = 15) who never suffered from malaria. Their ultrasonographic details of
      spleens, including the size, were compared. Besides other conspicuous differences
      in the ultrasonographic picture, spleen size was found significantly decreased (p
      < 0.01) in the group who had been affected by P. falciparum malaria; the smallest
      measured 7.8 cms. In P. vivax group the decrease was not significant (p < 0.1),
      but was highly significant in inhabitants of endemic falciparum region (p <
      0.001). The present study establishes the 'Small Spleen' and looks at echotexture
      pattern variations thereof for the first time.

PMID- 9282609
TI  - Post transplant diabetes mellitus in live related renal allograft recipients: a
      single centre experience.
AB  - The incidence of post-transplant diabetes mellitus (PTDM) was evaluated in 250
      patients who underwent live-related renal transplantation at our hospital between
      1978 and 1992. Twelve (4.8%) patients developed PTDM requiring drug therapy. PTDM
      occurred in 4 of 197 (2%) patients on conventional prednisolone-azathioprine
      immunosuppression as compared to 8 of 53 (15.1%) patients receiving cyclosporine
      in addition (triple-therapy). Three patients (25%) developed PTDM during or
      immediately following anti-rejection therapy with intravenous methylprednisolone.
      Eight patients (66.6%) developed PTDM within six months of transplantation.
      Majority of our patients (66.6%) could be managed successfully with oral
      hypoglycemic agents. Two patients (16.6%) showed spontaneous resolution of
      hyperglycemia within six months of onset of PTDM. Eleven patients (91.6%) were
      symptomatic for their hyperglycemia with two patients presenting as
      'pseudorejection' and one with diabetic ketoacidosis. Females were more
      predisposed to develop PTDM in our study (10% vs. 4.1%). HLA-B15 and DR 3 were
      the commonest phenotypes in our PTDM patients. No other known predisposing or
      triggering factors associated with PTDM were found in our patients. The current
      study suggests, that addition of cyclosporine to the conventional
      immunosuppression in live-related renal allograft recipients has contributed to
      an increased incidence of post-transplant diabetes mellitus. Close and regular
      blood sugar monitoring is thus recommended in post-transplant patients especially
      those on triple drug immunosuppression.

PMID- 9282612
TI  - Speaking at medical meetings.

PMID- 9282610
TI  - Nifedipine, captopril, metoprolol and nifedipine with metoprolol in hypertensive
      crisis in non-intensive care setting.
AB  - In 102 cases of severe hypertension (DBP > or = 115 mm Hg), with or without acute
      complications, efficacy and safety of SL Nifedipine 10 mg (NIF), SL Captopril 25
      mg (CAP), IV Metoprolol 15 mg (MET) and SL NIF + IV MET were studied in an
      inpatient trial. Maximum mean percent reduction in SBP was 13.3, 9.7, 15.7 and
      19.9 and in DBP was 21.2, 13.9, 12.5 and 20.4 with NIF, CAP, MET and NIF + MET
      respectively. A safe DBP of < or = 110 mm Hg (Kaplan) was achieved in 90, 61,
      72.2 and 95.2 percent of patients. A statistically significant fall in DBP was
      observed at 5 minutes with all regimens except CAP which was at 15 minutes. Mild
      side effects observed were palpitations and flushing (NIF n = 4), taste
      disturbances (CAP n = 3), heaviness of head (CAP n = 1) and giddiness (MET n = 2,
      NIF + MET n = 2). The trial data suggest that hypertensive crisis can be managed,
      without intensive care facility, with all four regimens; this implies significant
      cost containment.

PMID- 9282614
TI  - Splenic rupture in acute malaria.

PMID- 9282613
TI  - Spontaneous subcutaneous emphysema.

PMID- 9282615
TI  - Chiladiti's syndrome in an adult with chronic obstructive airway disease.

PMID- 9282616
TI  - Normal pregnancy in a case of Noonan syndrome with hypertrophic cardiomyopathy.

PMID- 9282617
TI  - An unusual presentation of chronic granulocytic leukaemia.

PMID- 9282618
TI  - True myotonia in a case of hypothyroidism.

PMID- 9282620
TI  - Carcinocythemia.

PMID- 9282619
TI  - Balint's syndrome.

PMID- 9282622
TI  - Intercostal herniation of the lung.

PMID- 9282621
TI  - An unusual hallucination with norfloxacin.

PMID- 9282623
TI  - Rajasthan malaria epidemic--1994--practical problems in prevention, diagnosis and
      treatment on the field.

PMID- 9282624
TI  - Traube's space percussion for detection of splenomegaly.

PMID- 9282625
TI  - Thrombotic thrombocytopenic purpura.

PMID- 9282626
TI  - Hepatitis B immunization policy for India.

PMID- 9282627
TI  - Meliodosis in India.

PMID- 9282628
TI  - Diabetes and oxidative stress.

PMID- 9282630
TI  - Electrocardiographic manifestations of healthy residents of a tribal Himalayan
      village.
AB  - Electrocardiograms of 984 healthy subjects residing in village Kalpa at the
      height of 9000 feet above sea level were studied. Right ventricular hypertrophy
      (RVH) was observed in 9 (0.914%) subjects. Electrocardiographic evidence of
      ischaemic heart disease was found in 6 (0.609%) subjects.

PMID- 9282629
TI  - Evaluation of oxidative stress in diabetics with or without vascular
      complications.
AB  - An excess of Oxidative Stress can occur either through an increase in the
      generation of free radicals and their metabolites (which overwhelm the protective
      capacity of the normal defence mechanisms of the body) or through a decrease in
      the protective ability of the body to withstand normal Oxidative Stress or both.
      Excessive Oxidative Stress plays an important role in the pathogenesis of
      diabetes and its chronic complications like retinopathy and nephropathy. Through
      various mechanisms, it plays a prominent role in the progression and acceleration
      of atherosclerosis. Free radicals being highly unstable due to their high
      reactivity are very difficult to measure accurately. Recourse is therefore taken
      to measure the compounds that are formed due to the activity of these free
      radicals. These compounds are relatively more stable and therefore can be
      measured as diene congugate and lipid peroxides. Another valuable measurement is
      to measure the levels of reduced glutathione in serum. Measurements of these
      products can be an excellent parameter to judge the metabolic control of
      diabetes.

PMID- 9282631
TI  - The hypoglycemic effect of chloroquine.
AB  - Ten persons were studied to observe the effect of intravenous administration of
      chloroquine on serum glucose level. Ten healthy individuals were given 800 mg of
      chloroquine in three hours infusion. There was a significant (p = 0.001) fall of
      25.86 per cent of initial blood glucose level in test group, while it was only
      10.47 per cent in control group. Therefore, it is emphasized that seriously III
      patients and those who are prore to hypoglycemia should be carefully monitored
      when giving IV chlorquine.

PMID- 9282632
TI  - Percutaneous renal biopsy using Monopty needle.
AB  - Forty six percutaneous renal biopsies (thirty one native and fifteen transplant
      kidneys) were performed using the Monopty needle, compared with equal number of
      biopsies performed using the Travenol Tru-cut needle. The core length of samples
      obtained ranged from 3-16 mm using Monopty and 5-13 mm using Tru-cut. Adequate
      tissue was obtained in 65.5% and 80.4% of cases with the use of Monopty and Tru
      cut respectively. Both the needles gave equal number of reuses. The use of Tru
      cut needle was associated with serious complications like gross haematuria
      requiring blood transfusions and perinephric haematoma in ten cases whereas only
      two cases developed haematuria when the Monopty needle was used. In view of its
      greater safety we have switched over to using the Monopty needle for percutaneous
      renal bipsies.

PMID- 9282633
TI  - Effect of age on P300 wave.
AB  - 30 healthy elderly males (mean age 77.4 +/- 4.3 yrs) were subjects in this study.
      Equal number of young males (mean age 22 +/- 3.5 years) and middle aged subjects
      (mean age 46 +/- 3.2 years) served as control. P300 wave was estimated using a
      Neuropack 4 model of Nihon Kohden EMG machine. We observed a significantly
      increased latency, poorly defined and non reproducible P300 wave in 90% old
      subjects while in young the latency was in normal limits and the wave was well
      defined and reproducible. We presume P300 could serve as a future potential
      marker of the neurophysiological basis of aging.

PMID- 9282634
TI  - Tetralogy of Fallot in adults--107 cases.
AB  - Clinical and haemodynamic profile of 107 adult patients above the age of 15 years
      with TOF was analysed. Cardiac catherization and selective cine-angiography were
      performed in all cases. Infundibular pulmonary stenosis, mal-alignment type of
      ventricular septal defect, mitral-aortic fibrous continuity and equal systolic
      pressures in both the ventricles and aorta were considered mandatory for the
      diagnosis of Tetralogy of Fallot. Aortic regurgitation was seen in 26 cases
      (24%), tricuspid regurgitation in 22 cases (21%), absent pulmonary valve in 3
      cases (3%), branch pulmonary artery stenosis in 9 case (8.4%), major
      aortopulmonary collaterals in 15 cases (14%), right atrial pressure was more than
      10 mmHg in 10 cases (11%) and right ventricular end diastolic pressure more than
      9 mmHg in 73 cases (68%). The left ventricular end diastolic pressure was above
      13 mmHg in 58 cases (54%).

PMID- 9282635
TI  - HLA association with sarcoidosis and diffuse interstitial pulmonary fibrosis.
AB  - HLA typing was performed on 18 patients suffering from sarcoidosis and 30
      patients suffering from diffuse interstitial pulmonary fibrosis. One hundred
      normal healthy people ethnically matched served as the controls. On statistical
      analysis, the corrected 'p' value of all the HLA antigens for both the patient
      groups was non significant. The results therefore suggest that there is no
      particular HLA antigen associated with sarcoidosis and diffuse interstitial
      pulmonary fibrosis.

PMID- 9282636
TI  - An epidemiological study of coronary heart disease in different ethnic groups in
      Delhi urban population.
AB  - A community based epidemiologival survey of coronary heart disease (CHD) was
      carried out on a random urban sample of 13,560 adults of different ethnic groups
      in Delhi. CHD was diagnosed either on the basis of clinical history, supported by
      documentary evidence of treatment in hospital/home or on the ECG evidence in
      accordance with Minnesota Code. The prevalence rate of CHD on clinical basis per
      1000 adults was the highest in Sikhs (47.3), lowest in Muslims (22.8) and
      identical in Hindus (31.8) and Christians (31.2). The prevalence rate/1000 of
      silent CHD on the basis of ECG was high in Muslims (89.5) and Sikhs (87.3), low
      in Christians (25.0) and intermediate in Hindus (60.0). The Sikhs showed the
      highest prevalence rate of myocardial infarct (MI) (15.5) and angina (AP) (31.8)
      compared to other communities. The prevalence rate of CHD on clinical basis was
      higher in males than females in all communities. The prevalence of silent CHD was
      higher in females in Hindus and Sikhs but in Muslims it was higher in men (94.8)
      than in women (85.2). The wide variations in prevalence rates of CHD in different
      ethnic groups cannot be explained satisfactorily on the basis of conventional
      risk factors and support the multifactorial etiological character of CHD.

PMID- 9282637
TI  - Evaluation of amlodipine in mild to moderate hypertension--a clinical report.
AB  - Twenty two patients having mild to moderate hypertension were treated with a
      single daily dose of amlodipine for 4 weeks. Satisfactory response defined as
      final diastolic blood pressure < 90 mm of Hg and a reduction from baseline values
      > 10 mm of Hg could be achieved in 81.8% of patients in supine position and 70%
      of patients in standing position. Thirteen patients responded to 5 mg dose and 9
      patients required 10 mg. Postural hypotension and reflex tachycardia were absent.
      Three patients has mild leg cramps and constipation. No deleterious effects were
      observed on liver, kidney and hemopoetic function, or on E.C.G. Changes.
      Amlodipine given once daily is effective and safe, and is a useful addition to
      the existing armamentarium of antihypertensive drugs.

PMID- 9282638
TI  - Study of ipratropium bromide inhalation in stable asthma.
AB  - An open two weeks short term trial of Ipratropium Bromide (IB) inhalation (0.02
      mg per dose) was carried out in 20 stable asthamatics to study its efficacy and
      safety. Early significant rise in PEFR (P < 0.001) and FEV1 (P < 0.05) was
      observed after 15 min of IB inhalation and reached significant peak (P < 0.01)
      after 1 hour which was persistent beyond three hours after IB inhalation. No side
      effects were observed. It was concluded that Ipratropium Bromide Imhalation is
      safe and has efficient bronchodilatory effect on short term basis in stable
      asthmatics.

PMID- 9282639
TI  - Withdrawal of antiepileptic drugs: a therapeutic dilemma.

PMID- 9282640
TI  - Liposomes as drug delivery system in leishmaniasis.

PMID- 9282641
TI  - HIV and tuberculosis.

PMID- 9282642
TI  - Immunology of AIDS.

PMID- 9282643
TI  - Acute myocardial injury in aluminium phosphide poisoning.

PMID- 9282644
TI  - Organophosphorous compound poisoning : prolonged therapy in absence of
      intermediate neurotoxic syndrome.

PMID- 9282645
TI  - Pulmonary fibroma--a rare tumour.

PMID- 9282646
TI  - HIV-associated staphylococcal pyomyositis.

PMID- 9282647
TI  - Early repolarization variant versus myocardial ischaemia.

PMID- 9282648
TI  - Leucodystrophic CT changes in Wilson's disease.

PMID- 9282649
TI  - Chronic cerebral malaria--is there such a clinical entity?

PMID- 9282650
TI  - Drugs and ECG changes.

PMID- 9282651
TI  - Overcoming the problem of poor inhaler technique.

PMID- 9282652
TI  - Diagnostic aspiration of hydatid cyst of liver--changing view.

PMID- 9282653
TI  - Salmonella bacteremia presenting with visual loss.

PMID- 9282655
TI  - Empirical treatment for PCP in HIV-infected patients--justified?

PMID- 9282654
TI  - Anticoagulants and thyroid.

PMID- 9282656
TI  - Urinary retention: an unusual presentation of rabies.

PMID- 9282658
TI  - Proliferation of medical associations.

PMID- 9282657
TI  - Coexistence of enteric fever with malaria.

PMID- 9282660
TI  - Modified antimalarial treatment for chloroquin resistant plasmodium falciparum
      infection.

PMID- 9282659
TI  - Zinc in rheumatic heart valves.

PMID- 9282661
TI  - Henoch schonlein purpura in adults associated with hepatitis B antigen.

PMID- 9282662
TI  - Safety of thrombolysis during mensturation.

PMID- 9282663
TI  - Pyeloureteritis cystica.

PMID- 9282664
TI  - Chronic amebiasis--treat couples.

PMID- 9282665
TI  - Combined toxicity due to alcohol and aluminium phosphide.

PMID- 9282667
TI  - Vivacitas.

PMID- 9282666
TI  - How can we protect our endothelium?

PMID- 9282668
TI  - Neuroticism and stressful life events in patients with non-ulcer dyspepsia.
AB  - Hindi adaptation of the Middlesex Hospital Questionnaire (MHQ), Brief Psychiatric
      Rating Scale and Presumptive Stressful Life Events Scale were used to measure
      neuroticism, psychiatric morbidity and stressful life events in 35 patients with
      non-ulcer dyspepsia (NUD), 22 cass of peptic ulcer disease (PUD), 65 irritable
      bowel syndrome (IBS) and 45 age and sex matched healthy controls. NUD subjects
      had significantly higher total MHQ scores (28.8 +/- 11.3; p < 0.001) and scores
      in subscales of somatization (7.8 +/- 3.4; p < 0.001) and hysterical personality
      traits (5.5 +/- 2.8; p < 0.01) compared to healthy controls. MHQ scores in IBS
      subjects was significantly higher than in NUD, but in PUD subjects it was in
      between NUD and healthy controls. Psychiatric morbidity, as assessed by Brief
      Psychiatric Rating Scale, was significantly higher in patients with NUD and IBS
      than in normal controls. Stressful Life event score was statistically similar in
      all the groups.

PMID- 9282669
TI  - Comparison of MR angiography with contrast angiography for the diagnosis of
      carotid artery stenosis.
AB  - To assess the accuracy of MR angiography for screening vascular stenosis of the
      extracranial carotid arteries, 20 consecutive patients with suspected
      extracranial carotid atherosclerotic disease were evaluated with time-of-flight
      MR angiography and intra-arterial contrast angiography. Both studies were
      independently reviewed by three observers in a blinded manner. The internal
      carotid arteries were graded as either normal or mildly stenotic (0%-29%),
      moderately stenotic (30%-69%), severely stenotic (70%-99%) or occluded. Results
      of the study indicate that time-of-flight MR angiography has a high rate of
      agreement with contrast angiography and is an accurate screening technique of the
      common carotid bifurcation in patients with suspected carotid stenosis.

PMID- 9282671
TI  - Allergic fungal sinusitis: incidence and clinical and pathological features of
      seven cases.
AB  - Allergic fungal sinusitis, like allergic bronchopulmonary fungal disease, is a
      noninvasive inflammatory process. It manifests as recurrent nasal polyposis.
      Histologically the characteristic feature is the presence of thick mucin with
      dense collections of degenerating eosinophils and Charcot-Leyden crystals
      (allergic mucin). Demonstration of fungal hyphae in allergic mucin is diagnostic
      of the disease. We reviewed 85 cases of nasal polyposis operated upon during a
      period of four years. Allergic fungal sinusitis was diagnosed in seven (8.2%)
      cases on the basis of presence of allergic mucin and fungal hyphae. History of
      previous nasal polypectomy was present in four of the seven cases, and in six of
      the remaining 78. There were no clinical or radiological features that could
      distinguish the cases of allergic fungal sinusitis from the rest. Aspergillus
      fumigatus, Mucor and Cladosporium were cultured from one case each.

PMID- 9282670
TI  - Alterations in circulating thyroid hormones in Indian smokers (bidi and
      cigarette).
AB  - T4, T3 and TSH were estimated in 56 bidi and 50 cigarette smokers and their mean
      estimates were compared with the corresponding values in 25 healthy non-smokers.
      T4, T3 and their ratios were significantly lower in both bidi and cigarette
      smokers (p < 0.001). Circulating TSH in both groups of smokers was similar to
      that in nonsmokers. T4 and T4/T3 were lower in bidi smokers compared to those in
      cigarette smokers (p < 0.05 and < 0.01, respectively). Severity of smoking
      affected T4/T3, and TSH in bidi smokers and T4 in cigarette smokers. Normal TSH
      excluded any significant decrease in thyroid function in smokers. The alterations
      in circulating T4 and T3 might have been influenced by thyroid hormone
      production, protein binding as well as peripheral metabolism of T4 by adverse
      constituents of bidi/cigarette smoke.

PMID- 9282672
TI  - Chloroquine resistant falciparum malaria in the Andamans.

PMID- 9282673
TI  - Autonomic dysfunction with special reference to cardiovascular responses in
      patients with raised intracranial tension.

PMID- 9282675
TI  - Angiopathy in diabetes mellitus.

PMID- 9282674
TI  - Acute myeloblastic leukemia in adults.

PMID- 9282676
TI  - Transjugular intrahepatic portacaval shunt (TIPS).

PMID- 9282677
TI  - Clinical significance of L-arginine--nitric oxide system.

PMID- 9282679
TI  - Nephrotic syndrome--a rare presenting feature in non-Hodgkin's lymphoma.

PMID- 9282678
TI  - Transcatheter indigeneous coil embolization in recurrent massive hemoptysis
      secondary to post-tubercular bronchiectasis.

PMID- 9282680
TI  - Wernicke's encephalopathy: clinical and CT findings.

PMID- 9282681
TI  - Neurocysticercosis--an unusual presentation.

PMID- 9282682
TI  - Fever of unknown cause presenting as Catatonia.

PMID- 9282683
TI  - CMV retinitis and dementia in an Indian with AIDS.

PMID- 9282684
TI  - Intramedullary cysticerci.

PMID- 9282685
TI  - Fibrodysplasia ossificans progressiva.

PMID- 9282686
TI  - Octreotide and ketoconazole for persistent ectopic ACTH Cushing's disease due to
      mediastinal carcinoid.

PMID- 9282687
TI  - Iatrogenic median and femoral neuropathy.

PMID- 9282688
TI  - Non reactive tuberculosis presenting as massive splenomegaly.

PMID- 9282689
TI  - Ventricular tachycardia following organophosphorus poisoning.

PMID- 9282690
TI  - Lymphoma presenting as a chest wall mass.

PMID- 9282691
TI  - Unnecessary emphasis on blast morphology in an inadequately worked up case of
      acute leukemia.

PMID- 9282692
TI  - Limited cutaneous scleroderma induced by pentazocine abuse.

PMID- 9282693
TI  - Acute viral cholecystitis in viral hepatitis.

PMID- 9282694
TI  - Chlorpromazine induced diabetes mellitus.

PMID- 9282695
TI  - Neuropsychiatric manifestations of salmonella infection.

PMID- 9282696
TI  - Phenformin induced lactic acidosis.

PMID- 9282697
TI  - Downs' syndrome with acute myeloid leukemia.

PMID- 9282698
TI  - Chickenpox in adulthood.

PMID- 9282699
TI  - Cranial nerve involvement in meningoencephalitis.

PMID- 9282700
TI  - Food intakes of US children and adolescents compared with recommendations.
AB  - OBJECTIVES: To determine the proportion of youth meeting national recommendations
      for food group intake and to identify food intake patterns. DESIGN: The US
      Department of Agriculture's 1989-1991 Continuing Surveys of Food Intakes by
      Individuals were used to estimate food intake. Intake was determined from 3 days
      of diet by disaggregating foods into their component ingredients and using
      weights that correspond to servings. PARTICIPANTS: The sample included 3307
      youth, 2 to 19 years of age, living in the 48 conterminous United States. Main
      Outcome Measures. Mean number of servings and percentage of individuals meeting
      national recommendations for food group intake according to demographic
      characteristics, patterns of intake, and nutrient profiles associated with each
      pattern. RESULTS: Mean numbers of servings per day were below minimum
      recommendations for all food groups except the dairy group (ages 2 to 11).
      Percentages of youth meeting recommendations ranged from approximately 30% for
      fruit, grain, meat, and dairy to 36% for vegetables. Sixteen percent of youth did
      not meet any recommendations, and 1% met all recommendations. The pattern of
      meeting all recommendations resulted in nutrient intakes above the recommended
      dietary allowances and was high in fat. Conversely, meeting none of the
      recommendations resulted in intakes well below the recommended dietary allowances
      for some nutrients. Total fat and added sugars averaged 35% and 15% of energy,
      respectively, and levels were similar among most demographic groups. CONCLUSION:
      Children and teens in the United States follow eating patterns that do not meet
      national recommendations. Nutrition education and intervention are needed among
      US children.

PMID- 9282701
TI  - Parents can dose liquid medication accurately.
AB  - OBJECTIVE: To determine whether parental errors in dosing liquid medication can
      be decreased through education. DESIGN: Randomized convenience sample stratified
      to three study groups. SETTING: General pediatric clinic, largely indigent and
      Latino. PATIENTS: A total of 45 English-speaking and 45 Spanish-speaking children
      diagnosed with otitis media and treated with an antibiotic suspension.
      INTERVENTION: Group 1 patients received the prescription and verbal instructions.
      Group 2 patients received the prescription and a syringe, then the correct dose
      was demonstrated. Group 3 patients received the prescription, a syringe with a
      line marked at the correct dose, and a demonstration. After returning from the
      pharmacy, parents administered the medication under observation. Parents in group
      1 used a dispensing device similar to that planned for home use. The other groups
      used the syringe. After observation but before discharge, everyone received a
      syringe with a line marked at the correct dose. Patients were seen again at
      approximately 1 month, and parents demonstrated how much medication they had
      administered. MAIN OUTCOME MEASURE: Percent of parents who administered the
      correct dose. RESULTS: Patients in group 1 received between 32% and 147% of the
      correct dose, with only 11 of 30 (37%) receiving the correct dose (+/-0.2 mL). In
      group 2, 25 of 30 (83%) parents administered the correct dose, and in group 3, 30
      of 30 (100%) gave the correct dose. Simultaneous logistic regression indicated
      that accuracy of dosage differed across instructional groups and language. At
      follow-up, 23 of 26 parents demonstrated the correct dose. CONCLUSION: Education
      can decrease medication dosing errors made by both Spanish-speaking and English
      speaking parents. Effectiveness was also shown at follow-up.

PMID- 9282702
TI  - Outpatient management practices associated with reduced risk of pediatric asthma
      hospitalization and emergency department visits.
AB  - OBJECTIVES: Effective outpatient care is believed to prevent hospitalization and
      emergency department (ED) visits resulting from childhood asthma. The aim of this
      study was to suggest priority areas for intervention by identifying outpatient
      management practices associated with the risk of these adverse outcomes in a
      large population. METHODS: This case-control study included children aged 0 to 14
      years with asthma who were members of a regional health maintenance organization.
      Cases were children undergoing either a hospitalization or an ED visit for asthma
      during the study period. Control subjects were children with asthma without a
      hospitalization or an ED visit during the study period who were matched to
      patients on age, gender, and number of asthma-related hospitalizations in the
      past 24 months. Data on provider and parent asthma management practices were
      collected using chart review, closed-ended telephone interviews with parents, and
      computerized use databases. Multivariate analyses were conducted using
      conditional logistic regression models. RESULTS: Data were collected on 508 cases
      and 990 control subjects. A total of 43% of cases were reported by their parents
      to have moderately severe or severe asthma, compared with 20% of control
      subjects. Parents of cases with hospitalization were less likely than control
      subjects to have a written asthma management plan (44% vs 51%) and to report
      washing bedsheets in hot water at least twice a month (77% vs 86%). Cases with
      hospitalization were more likely to have a nebulizer (74% vs 56%). In the final
      multivariate model, race/ethnicity was not associated with having had either a
      hospitalization or an ED visit, as was lower socioeconomic status. Having a
      written asthma management plan [odds ratio (OR): 0.54; 95% confidence interval
      (CI): 0.30, 0.99] and washing bedsheets in hot water at least twice a month (OR:
      0.45; 95% CI: 0.21, 0.94) were associated with reduced odds of hospitalization.
      Having a written asthma management plan (OR: 0.45; 95% CI: 0.27, 0.76) and
      starting or increasing medications at the onset of a cold or flu were associated
      with reduced odds of making an ED visit. CONCLUSIONS: Practices that support
      early intervention for asthma flare-ups by parents at home, particularly written
      management plans, are strongly associated with reduced risk of adverse outcomes
      among children with asthma.

PMID- 9282703
TI  - Predictors of injury mortality in early childhood.
AB  - OBJECTIVE: To study the association between maternal/infant characteristics and
      mortality from injury for children 0 through 4 years of age. DESIGN: Historical
      cohort. SETTING: State of Tennessee. PARTICIPANTS: Children 0 through 4 years of
      age at any time between January 1, 1985 and December 31, 1994. We linked birth
      certificates and US census data to obtain information on maternal age, race,
      education, neighborhood income, parity, use of prenatal care, residence location,
      infant's gender, and gestational age. MAIN OUTCOME MEASURES: The outcome was
      death from injury, as determined from linked death certificates. The incidence
      density rates for each stratum (defined by maternal/child characteristics) were
      calculated by dividing the number of injury deaths by child years in the stratum.
      We used multivariate analysis to assess the independent contribution of each
      characteristic to risk of injury death. RESULTS: There were 1 035 504 children 0
      through 4 years of age who contributed 3 414 436 child years. There were 803
      deaths from injury, ie, 23.5 deaths per 100 000 child years. In the multivariate
      analysis, children had at least a 50% increased risk of injury mortality if they
      were born to a mother who had less than a high school education (relative risk
      [RR] = 2.88; 95% confidence interval [CI]: 1.92-4.34) compared with a college
      education, was <20 years of age (RR = 2.42; 95% CI: 1.76-3.31) compared with >30
      years, or had >2 other children (RR = 2.97; 95% CI: 2.29-3.85) compared with no
      other children. Neither race nor income was significantly associated with
      childhood injury mortality in the multivariate analysis. Classification of
      children by maternal education, age, and parity defined a pronounced risk
      gradient in which high-risk children had an injury mortality rate >15 times that
      of low-risk children. The steep risk gradient was present for both infants (24
      fold increase for high-risk children) and children 1 through 4 years of age (13
      fold increase for high-risk children). If the injury mortality rate for all
      children were equal to that of the low-risk group, 614/803 (76.3%) of injury
      deaths would not have occurred. CONCLUSIONS: For young children, maternal
      education, age, and parity are strongly and independently associated with injury
      mortality. These factors define a steep gradient of risk, suggesting that many
      injury deaths could be prevented.

PMID- 9282704
TI  - Neonatal morbidity after elective repeat cesarean section and trial of labor.
AB  - OBJECTIVE: To evaluate neonatal outcomes after an elective repeat cesarean
      section (ERCS) compared with a trial of labor (TOL). POPULATION AND METHOD: All
      mothers who underwent previous cesarean section and delivered singleton infants
      at term gestation were identified during a 1-year period. Neonatal outcomes were
      compared between infants delivered by ERCS (n = 497) and those delivered by TOL
      (n = 492), and between infants delivered by a successful (n = 336) and a failed
      (n = 156) TOL. A cohort of mothers and their term infants delivered by routine
      vaginal delivery were also identified. RESULTS: Infants delivered by ERCS had an
      increased rate of transient tachypnea compared with infants born by TOL (6% vs
      3%). Compared with routine vaginal deliveries, the adjusted odds ratio of
      developing any respiratory problem after an ERCS was 2.3 (95% confidence interval
      [CI]: 1.4, 3.8), and for developing transient tachypnea was 2.6 (CI: 1.5, 4.5).
      In addition, two infants delivered by ERCS developed respiratory distress
      syndrome. Infants delivered after a TOL had increased rates of suspected and
      proven sepsis (5% vs 2% and 1% vs 0.1%, respectively). Compared with a successful
      TOL, the infants delivered by cesarean section after a failed TOL had more
      neonatal morbidity and had a longer hospital stay (4.8 +/- 2 vs 3.1 +/- 2 days).
      The odds ratio for developing any respiratory illness after a failed TOL was 2.1
      (95% CI: 1.1, 4.1), for suspected sepsis was 4.8 (95% CI: 2.6, 9.0), and for
      proven sepsis was 19.3 (95% CI: 2.0, 187). Neonatal outcomes after a successful
      TOL were similar to routine vaginal births. CONCLUSION: Infants born by ERCS are
      at increased risk for developing respiratory problems compared with those born by
      TOL. However, TOL is associated with increased rates of suspected and proven
      sepsis. This appears to be limited to infants delivered by cesarean section after
      a failed TOL.

PMID- 9282705
TI  - Apnea frequently persists beyond term gestation in infants delivered at 24 to 28
      weeks.
AB  - BACKGROUND: Apnea of prematurity remains among the most commonly diagnosed
      conditions in the Newborn Intensive Care Unit and may prolong hospital stays in
      some infants. Because survival of extremely premature infants has improved
      markedly, the natural history of apnea in this population needs to be reassessed.
      OBJECTIVE: To document the natural history of recurrent apnea and/or bradycardia
      events in infants delivered at 24 to 28 weeks' gestation. METHODS: Medical
      records of all infants delivered at 24 to 28 weeks' gestation admitted to the
      Brigham and Women's Hospital Newborn Intensive Care Unit between January 1989 and
      March 1994 were reviewed to document the clinical course of apnea of prematurity.
      Subjects were included in the study sample if they were discharged home from the
      Brigham and Women's Hospital or after transfer to an affiliated hospital.
      Recordings of apnea and/or bradycardia events were based on nursing observations
      of monitor alarms and assessment of the infant's condition. RESULTS: Of 457
      eligible infants, 226 were included in the study sample and stratified by
      gestational age at birth assigned by the attending neonatologist. The time to
      resolution of recurrent apnea/bradycardia events was longer with lower
      gestational age at birth. Apnea/bradycardia events were frequently observed
      beyond 36 weeks' postconceptional age in all gestational age groups. The
      incidence of apnea persisting beyond 38 weeks postconceptional age was
      significantly higher in the 24- to 27-week infants combined compared with the 28
      week infants. CONCLUSIONS: Apnea of prematurity frequently persists beyond term
      gestation in infants delivered at 24 to 28 weeks' gestational age. These
      persistent apnea and/or bradycardia events may contribute to prolonged
      hospitalization. Programs to promote earlier discharge of premature infants
      should take into account the variability in resolution of apnea and specifically
      address management of persistent apnea.

PMID- 9282706
TI  - Purpuric phototherapy-induced eruption in transfused neonates: relation to
      transient porphyrinemia.
AB  - OBJECTIVE: Blue light phototherapy is commonly administered to neonates as
      treatment of indirect hyperbilirubinemia, often in conjunction with blood
      transfusions to treat hemolytic anemia. We observed a distinctive cutaneous
      complication of phototherapy in six neonates with hyperbilirubinemia.
      METHODOLOGY: We studied the clinical and histologic characteristics of the
      eruption, as well as the porphyrin levels in affected neonates. Five of the
      patients had erythroblastosis fetalis; the other had profound anemia from twin
      twin transfusion. All of the neonates developed purpuric patches at sites of
      maximal exposure to the phototherapy lights, with dramatic sparing at shielded
      sites within 24 hours after initiation of the phototherapy. On discontinuation of
      phototherapy, all eruptions cleared within 1 week. Examination of skin biopsy
      sections showed purpura without significant inflammation or keratinocyte
      necrosis. Plasma porphyrins (copro- and proto-) were elevated in the two patients
      in which they were assessed. CONCLUSIONS: The distribution of the eruption in
      areas exposed to light and presence of circulating porphyrins suggest that
      porphyrinemia may underlie the light-induced purpuric eruption. Additional
      studies will be required to determine definitively the mechanisms of both the
      purpuric phototherapy-induced eruption and the development of increased blood
      porphyrin levels in these transfused neonates.

PMID- 9282708
TI  - Factors associated with HIV testing among sexually active adolescents: a
      Massachusetts survey.
AB  - OBJECTIVE: To assess sexually active adolescents' knowledge, attitudes, and
      behaviors associated with human immunodeficiency virus (HIV) testing and to
      determine the factors important in their decision to obtain voluntary HIV
      testing. DESIGN: Anonymous, random, digit-dial telephone survey undertaken in
      1993. SETTING: Massachusetts households. PARTICIPANTS: Adolescents, 16 to 19
      years of age. RESULTS: Of the 567 adolescents surveyed who had sexual intercourse
      within the past year, 127 (22%) had received HIV testing, with 54 (10%) stating
      that this testing was for personal reasons. A "great deal" or "some" worry about
      getting HIV/acquired immunodeficiency syndrome (AIDS) was expressed by 51%, and
      56% felt that it was at least a little likely that they will get AIDS.
      Misconceptions were common about aspects of HIV testing: 35% did not believe or
      did not know that the HIV test results were kept in confidence, 19% thought that
      AIDS testers informed partners if the results were positive, and 30% did not
      think that the HIV test was very accurate. Although 92% (452/490) had seen a
      physician in the past year, only 30% (136/452) had ever discussed AIDS with a
      doctor. Multivariable analysis identified five factors as independently
      associated with voluntary adolescent HIV testing: 1) having had more than one
      sexual partner within the past year [odds ratio (OR): 2.9; 95% confidence
      interval (CI): 1.5, 5.5]; 2) believing that condoms are only somewhat effective
      at preventing the spread of AIDS (OR: 2. 6; 95% CI: 1.4, 4.8); 3) having
      discussed AIDS with a doctor (OR: 2. 6; 95% CI: 1.4, 4.8); 4) not having had a
      teacher discuss AIDS (OR: 2.2; 95% CI: 1.2, 4.2); and 5) believing that a
      positive test result means one has AIDS as opposed to carrying the virus (OR:
      2.0; 95% CI: 1.1, 3.7). High-risk behavior of infrequent condom use and a history
      of a sexually transmitted disease were not significantly associated with
      voluntary HIV testing. CONCLUSION: Among sexually active Massachusetts
      adolescents, voluntary HIV testing is uncommon. Teens who have had multiple
      sexual partners and who do not believe condoms are effective in preventing
      transmission were most likely to have been tested. Issues requiring clearer
      communication to patients include the testing process, its availability, and
      confidentiality. Physicians can play an influential role in the promotion of HIV
      testing by discussing HIV risk behaviors with patients and offering those at risk
      voluntary HIV counseling and testing.

PMID- 9282707
TI  - In vivo bone lead measurement in suburban teenagers.
AB  - OBJECTIVE: Bone represents a biologically active long-term storage site for lead,
      and bone lead data on teenagers are limited. Therefore, this study was designed
      to identify the distribution of bone lead in a teenage population and to explore
      the environmental and demographic factors associated with bone lead
      concentrations in young, nonoccupationally exposed subjects. DESIGN: A cross
      sectional study of bone lead levels in high school students. PARTICIPANTS: A
      total of 168 students at a suburban Boston high school. Subjects (90 boys, 78
      girls) ranged in age from 13.5 to 19 years and included 40% nonwhite minorities.
      Of the 168 subjects, 45 lived in homes constructed before 1960. None of the
      participants reported a history of lead poisoning. OUTCOME MEASURES: Tibial bone
      lead concentrations were measured in vivo for 60 minutes using K x-ray
      fluorescence. Lead exposure information was obtained by self-administered
      questionnaire. RESULTS: Point estimates of bone lead levels ranged from -7.15 to
      14.23 microg lead/g bone mineral (microg/g), (mean, 4.0 microg/g; standard
      deviation, 4.4 microg/g). The reported measurement uncertainties accompanying
      each of the point estimates ranged from 2.56 to 9.01 microg/g (mean, 3.9
      microg/g; standard deviation, 1.0 microg/g). Bone lead levels were not associated
      with the demographic factors of age, sex, or race. Additionally, current home
      conditions (housing age, traffic level) were not predictive of bone lead levels,
      even though these factors were predictive of in-home lead concentrations.
      CONCLUSIONS: These results demonstrate that although bone lead levels are
      measurable in this age group, the common predictors of blood and bone lead
      concentrations are not explanatory for bone lead levels.

PMID- 9282710
TI  - New lead screening guidelines from the Centers for Disease Control and
      Prevention: how will they affect pediatricians?

PMID- 9282709
TI  - The 1997 AAP guidelines for prevention of early-onset group B streptococcal
      disease. American Academy of Pediatrics.

PMID- 9282711
TI  - Dilution of intravenous N-acetylcysteine as a cause of hyponatremia.

PMID- 9282712
TI  - Juvenile dermatomyositis presenting with rash alone.

PMID- 9282713
TI  - Sarcoidosis presenting as bilateral testicular masses.

PMID- 9282714
TI  - Neurofibromatosis type 1 vasculopathy associated with lower limb hypoplasia.

PMID- 9282715
TI  - Prolonged viremia and immune response to human herpesvirus 7 in an infant with
      liver dysfunction.

PMID- 9282716
TI  - Needle length and injection technique for efficient intramuscular vaccine
      delivery in infants and children evaluated through an ultrasonographic
      determination of subcutaneous and muscle layer thickness.

PMID- 9282717
TI  - Central nervous system infection associated with Bartonella quintana: a report of
      two cases.

PMID- 9282719
TI  - Nonfamilial hypokalemic periodic paralysis and thyrotoxicosis in a 16-year-old
      male.

PMID- 9282718
TI  - Genital papillomavirus infection: clinical progression after varicella infection.

PMID- 9282720
TI  - Description of a painting.

PMID- 9282732
TI  - The oxygen-responsive transcriptional regulator FNR of Escherichia coli: the
      search for signals and reactions.
AB  - The FNR (fumarate and nitrate reductase regulation) protein of Escherichia coli
      is an oxygen-responsive transcriptional regulator required for the switch from
      aerobic to anaerobic metabolism. In the absence of oxygen, FNR changes from the
      inactive to the active state. The sensory and the regulatory functions reside in
      separate domains of FNR. The sensory domain contains a Fe-S cluster, which is of
      the [4Fe-4S]2+ type under anaerobic conditions. It is suggested that oxygen is
      supplied to the cytoplasmic FNR by diffusion and inactivates FNR by direct
      interaction. Reactivation under anoxic conditions requires cellular reductants.
      In vitro, the Fe-S cluster is converted to a [3Fe-4S]+ or a [2Fe-2S]2+ cluster by
      oxygen, resulting in FNR inactivation. After prolonged incubation with oxygen,
      the Fe-S cluster is destroyed. Reassembly of the [4Fe-4S]2+ cluster might require
      cellular proteins, such as the NifS-like protein of E. coli. In this review, the
      rationale for regulation of alternative metabolic pathways by FNR and other
      oxygen-dependent regulators is discussed. Only the terminal reductases of
      respiration, and not the dehydrogenases, are regulated in such a way as to
      achieve maximal H+/e- ratios and ATP yields.

PMID- 9282734
TI  - Arginine boxes and the argR gene in Streptomyces clavuligerus: evidence for a
      clear regulation of the arginine pathway.
AB  - The argR gene of Streptomyces clavuligerus has been located in the upstream
      region of argG. It encodes a protein of 160 amino acids with a deduced M(r) of
      17117 for the monomer. Transformants containing the amplified argR gene showed
      lower activity (50%) of the biosynthetic ornithine carbamoyltransferase (OTC)
      activity and higher levels (380%) of the catabolic ornithine aminotransferase
      (OAT) activity than control strains. Amplification of an arginine (ARG) box
      containing sequence results in a 2- to 2.5-fold derepression of ornithine
      acetyltransferase and OTC, suggesting that the repressor is titrated out.
      Footprinting experiments using the pure homologous arginine repressor (AhrC) of
      B. subtilis showed a protected 38 nt region (ARG box) in the coding strand
      upstream of argC. The protected region contained two tandemly repeated imperfect
      palindromic 18-nt ARG boxes. The repressor-operator interaction was confirmed by
      bandshift experiments of the DNA fragment containing the protected region. By
      computer analysis of the Streptomyces sequences available in the databases, a
      consensus ARG box has been deduced for the genus Streptomyces. This is the first
      example of a clear regulation of an amino acid biosynthetic pathway in
      Streptomyces species, challenging the belief that actinomycetes do not have a
      well-developed regulatory system of these pathways.

PMID- 9282733
TI  - Spontaneous duplication of a 661 bp element within a two-component sensor
      regulator gene causes phenotypic switching in colonies of Pseudomonas tolaasii,
      cause of brown blotch disease of mushrooms.
AB  - Spontaneous sectoring of Pseudomonas tolaasii colonies results in a phenotypic
      switch from the smooth, pathogenic form (designated 1116S) to the rough non
      pathogenic form (designated 1116R). This phenotypic switch can also be induced by
      mutation of the pheN master regulatory locus, which encodes a 99 kDa protein with
      homology to the conserved family of sensor regulator proteins. Southern blot
      analysis of genomic DNA from 1116S and 1116R probed with a 3.4 kb Xhol-BamHI
      fragment containing the pheN gene has revealed restriction fragment length
      polymorphisms in the pheN locus of 1116R. In order to characterize the genetic
      basis of this variation, the pheN locus (designated pheN') was cloned from 1116R
      and its nucleotide sequence determined. A 661 bp duplication was identified
      within pheN' introducing a frameshift mutation in the predicted pheN open reading
      frame (ORF). A resulting predicted ORF of pheN' designated ORF2 encodes a
      polypeptide of 706 amino acid residues, with a predicted molecular weight of 77
      kDa, and which lacks part of the PheN sensor domain. Southern blot analysis of
      genomic DNA using a probe within the duplicated sequence revealed the presence of
      two bands in 1116R but only one band in the 1116S form. Polymerase chain reaction
      (PCR) analysis of 25 independently isolated 1116R sectors using primers flanking
      the duplication site in pheN confirmed the presence of the duplicated 661 bp
      sequence within this region in all of the sectors and the absence of the
      duplicated sequence in spontaneous revertants from 1116R to 1116S. Northern blot
      analysis of RNA from 1116S and 1116R using a pheN probe showed that ORF2 was
      transcribed in the 1116R form. The presence of a truncated PheN protein in 1116R
      was verified by Western blot analysis of total cell protein using a LemA
      antiserum, which revealed the presence of 99kDa and 77kDa cross-reactive bands in
      1116S and 1116R respectively. It is concluded that the spontaneous colony
      sectoring event that results in the 1116R phenotypic variant form of P. tolaasii
      arises owing to a 661 bp DNA duplication within the 5' end of the pheN gene,
      which results in loss of the periplasmic sensor domain of PheN and elimination of
      normal PheN function.

PMID- 9282735
TI  - Beta, a novel repetitive DNA element associated with tRNA genes in the pathogenic
      yeast Candida albicans.
AB  - We have identified a novel 399 bp repetitive DNA element (which we designate
      beta) 9bp upstream of a seryl-tRNA(CAG) gene in the genome of Candida albicans.
      There are two copies of the seryl-tRNA(CAG) gene, one on each homologue of
      chromosome VI, and the beta element is found upstream of one copy of the gene in
      C. albicans strain 2005E. The beta element is not present upstream of either copy
      of the seryl-tRNA(CAG) gene in eight other laboratory strains of C. albicans
      tested, but was detected in this location in several fresh clinical isolates.
      Southern blot analysis indicated that there are approximately eight copies of the
      beta element per diploid C. albicans genome and that it is a mobile element,
      being present on at least two different chromosomes. Three unique genomic DNA
      clones containing the beta element were isolated from strain 2005E; in each case,
      a different tRNA gene was found immediately adjacent to the beta element. Three
      new tRNA genes from C. albicans have thus been identified: tRNA(Asp), tRNA(Ala)
      and tRNA(Ile). The beta element shows no significant sequence homology to other
      known prokaryotic or eukaryotic repetitive elements, although an 8 bp repeat at
      the 3' end of the element is identical to that of the Ty3 retrotransposable
      element of Saccharomyces cerevisiae. We propose that the beta element is a solo
      long terminal repeat (LTR) sequence of a Ty3/gypsy-like transposable element in
      C. albicans that is closely associated with tRNA genes.

PMID- 9282736
TI  - The ssb-113 allele suppresses the dnaQ49 mutator and alters DNA supercoiling in
      Escherichia coli.
AB  - Mutations in the dnaQ gene, which encodes the proofreading epsilon-subunit of the
      DNA polymerase III holoenzyme, lead to a mutator phenotype caused by enhanced
      error rates during DNA replication. In this paper, we studied the influence of
      ssb mutations on the dnaQ49 mutator, because of the involvement of SSB protein in
      DNA replication. We found that the ssb-113 mutation suppresses the mutator
      phenotype of dnaQ49. The suppression effect resulted from an enhanced expression
      of the dnaQ49 allele as determined by experiments with gene fusions. S1 nuclease
      analysis revealed that the increased dnaQ expression is based on transcriptional
      activation of the dnaQP2 promoter. This seems to be the consequence of an
      increased DNA supercoiling in the ssb-113 mutant, which also influenced further
      functions that are sensitive to alterations in DNA supercoiling. These results
      support the hypothesis that the expression of the epsilon-subunit of DNA
      polymerase III may additionally be modulated by DNA supercoiling, and suggest a
      possible role for DNA topology in mutagenesis.

PMID- 9282737
TI  - Interactions of the components of the general secretion pathway: role of
      Pseudomonas aeruginosa type IV pilin subunits in complex formation and
      extracellular protein secretion.
AB  - The general secretion pathway (GSP), found in a wide range of bacteria, is
      responsible for extracellular targeting of a subset of proteins from the
      periplasm. In Pseudomonas aeruginosa, the GSP requires the participation of 12
      proteins, of which XcpT, XcpU, XcpV, XcpW are homologues of PilA, the major
      subunit of type IV pili. The interaction between the pilin-like Xcp proteins was
      investigated using bifunctional crosslinking reagents. Cross-linking analysis of
      whole cells of wild-type P. aeruginosa, followed by immunoblot analysis, revealed
      a 34-kDa XcpT-containing complex. This complex was shown to consist of XcpT/PilA
      heterodimers. The role of PilA in the GSP was examined, using P. aeruginosa
      mutants in the pilA gene, or in rpoN, a gene regulating pilA expression. Each
      mutant showed a significant reduction in the efficiency of extracellular protein
      secretion, and this defect could be restored by expression of the cloned pilA
      gene in the mutant cells. The formation of the PilA/XcpT complex did not require
      XcpR or XcpQ, two other components of the secretion machinery, nor did it require
      the pilus biogenesis factors PilB and PIlC. The dimeric XcpT/PilA complex was
      also formed in a pilD mutant, which lacks the leader peptidase enzyme,
      demonstrating that the leader peptide at the N-terminus or PilA or XcpT did not
      have to be removed for the dimerization to occur. XcpW and XcpU can also be
      crosslinked to form dimeric complexes with PilA. When expression of XcpT is
      increased, its homodimers, as well as XcpT/XcpW heterodimers, can be detected.
      Finally, an oligohistidine-tagged XcpT was shown to form stoichiometric complexes
      with PilA, and with XcpT, U, V and W. These dimers were co-purified by nickel
      affinity chromatography. The results of this study suggest that XcpT can form
      heterodimers with PilA, and Xcp U, V and W, which may be assembly intermediates
      of the secretion apparatus. Alternatively, these may represent dynamic
      intermediates that facilitate protein secretion by continuous association and
      dissociation. The requirement for PilA for efficient protein secretion argues for
      a critical role played by PilA in two related processes during P. aeruginosa
      infections: formation of an adhesive pilus organelle and secretion of exoenzymes.

PMID- 9282738
TI  - Functional analysis of chimerical plasma membrane H+-ATPases from Saccharomyces
      cerevisiae and Schizosaccharomyces pombe.
AB  - The plasma membrane H+-ATPase from the fission yeast Schizosaccharomyces pombe
      does not support growth of H+-ATPase-depleted cells of the budding yeast
      Saccharomyces cerevisiae, even after deletion of the enzyme's carboxy terminus.
      Functional chimerical H+-ATPase proteins in which appropriate regions of the S.
      pombe enzyme were replaced with their S. cerevisiae counterparts were generated
      by in vivo gene recombination. Site-directed mutagenesis of the H+-ATPase
      chimeras showed that a single amino acid replacement, tyrosine residue 596 by
      alanine, resulted in functional expression of the S. pombe H+-ATPase. The reverse
      Ala-598-->Tyr substitution was introduced into the S. cerevisiae enzyme to better
      understand the role of this alanine residue. However, no obvious effect on ATPase
      activity could be detected. The S. cerevisiae cells expressing the S. pombe H+
      ATPase substituted with alanine were enlarged and grew more slowly than wild-type
      cells. ATPase activity showed a more alkaline pH optimum, lower K(m) values for
      MgATP and decreased Vmax compared with wild-type S. cerevisiae activity. None of
      these kinetic parameters was found to be modified in glucose-starved cells,
      indicating that the S. pombe H+-ATPase remained fully active. Interestingly,
      regulation of ATPase activity by glucose was restored to a chimera in which the
      S. cerevisiae sequence spans most of the catalytic site.

PMID- 9282739
TI  - The membrane-bound cell division protein DivIB is localized to the division site
      in Bacillus subtilis.
AB  - The cell division gene divIB of Bacillus subtilis is essential for the normal
      rate of growth and division. The gene product, DivIB, is a membrane-bound protein
      in which the bulk of the protein (at the C-terminal end) is on the exterior
      surface of the cell membrane. DivIB is involved in the early stages of septum
      formation, but its exact role in cell division is unknown. To gain more
      information about the mode of action of DivIB in septum formation, we determined
      the location of DivIB within the cell membrane using immunofluorescence. This
      immunolocalization approach established that DivIB becomes localized to the
      division site before visible septation and remains localized to this site
      throughout the division process. Various DivIB immunostaining patterns were
      observed in immunofluorescence experiments and, together with cell length and
      nucleoid distance measurements, have allowed us to propose two models to describe
      DivIB localization during the cell cycle.

PMID- 9282740
TI  - InlB: an invasion protein of Listeria monocytogenes with a novel type of surface
      association.
AB  - Listeria monocytogenes is an intracellular bacterial pathogen that expresses
      several surface proteins critical for the infectious process. Such proteins
      include InlA (internalin) and InlB, involved in bacterial entry into the host
      cell, and ActA, required for bacterially induced actin-based motility. Although
      the molecular mechanisms of attachment of InlA and ActA have been characterized,
      essentially nothing is known about how InlB is anchored to the bacterial surface.
      Using a genetic approach, we demonstrate that the last 232 amino acids of InlB
      are both necessary and sufficient for anchoring this protein to the bacterial
      surface. An InlB mutant protein deleted for the last 232 amino acids was secreted
      and not detected at the cell surface. A 'domain-swapping' strategy in which these
      232 amino acids were used to replace the normal cell wall-anchoring domain of
      InlA resulted in a chimeric protein that was anchored to the cell surface and
      able to confer entry. Interestingly, surface association of InlB also occurred
      when InlB was added externally to bacteria, suggesting that association may be
      able to occur after secretion. This association was productive for invasion, as
      it conferred bacterial entry into host cells. The C-terminal anchoring region in
      InlB contains 80-amino-acid repeats beginning with the sequence GW that is also
      present in a newly identified surface-associated bacteriolysin of L.
      monocytogenes, called Ami. Addition of GW repeats to the C-terminal of InlB
      improves anchoring of the protein to the cell surface. These and other data
      suggest that such 'GW' repeats may constitute a novel motif for cell-surface
      anchoring in Listeria and other Gram-positive bacteria. This motif may have
      important consequences for the release of surface proteins involved in
      interactions with eukaryotic cells.

PMID- 9282741
TI  - The use of flash photolysis for a high-resolution temporal and spatial analysis
      of bacterial chemotactic behaviour: CheZ is not always necessary for chemotaxis.
AB  - The purpose of this work was to develop a high-resolution analysis of behaviour
      as an assay of the physiological consequences of mutations in the che genes and
      also to examine the role of CheZ in chemotaxis. Recent advances in flash
      photolysis have made it possible to expose cells to an unstable chemical gradient
      created by a square-wave increase in attractant concentration. The response of
      individual cells can be tracked in the order of milliseconds using real-time
      motion analysis. The tumble frequency of wild-type Escherichia coli exposed to
      photoreleased aspartate falls very quickly to smooth-swimming levels, and the
      swimming speed of these cells rises. As a consequence of these behavioural
      changes, there is an increase in the number of bacteria present in the centre of
      the flashed area, that is the bacteria's response to the transient gradient
      generated by flash photolysis was to swim into the centre of the flash area. This
      allowed the rapid quantitative measurement of chemotaxis. Deletion of various che
      genes resulted in predictable changes in chemotactic behaviour. cheZ null mutants
      are non-chemotactic when measured by classical techniques but demonstrate a
      definite chemotactic response to photoreleased attractant.

PMID- 9282742
TI  - FtsN, a late recruit to the septum in Escherichia coli.
AB  - The localization of FtsN in Escherichia coli was inves tigated by
      immunofluorescence microscopy. FtsN is an essential cell division protein with a
      simple bitopic topology, a short N-terminal cytoplasmic segment fused to a large
      carboxy periplasmic domain through a single transmembrane domain. FtsN was found
      to localize to the septum in a ring pattern similar to that observed for FtsZ and
      FtsA, although the frequency of cells with rings was less. A MalG-FtsN fusion was
      also localized to the septum, indicating that the information for FtsN
      localization is supplied by its periplasmic domain. FtsN localization was
      dependent upon the prior localization of FtsZ and FtsA and required the function
      of FtsI and FtsQ. Consistent with FtsN functioning after FtsZ, Z rings were
      observed in a mutant depleted of FtsN.

PMID- 9282743
TI  - Oriented DNA binding by one-armed lambda repressor heterodimers and contacts
      between repressor and RNA polymerase at P(RM).
AB  - Bacteriophage lambda repressor activates transcription from P(RM) by contacting
      the sigma subunit of E. coli RNA polymerase. Although mutations in repressors
      that are defective in activation affect exposed residues in the repressor
      operator co-crystal, the subunit in repressor dimers that is responsible for
      activation has not been determined experimentally. Here, we describe an oriented
      heterodimer approach using one-armed repressor-leucine zipper fusion proteins to
      resolve this question. Protection against methylation of operator DNA in vitro by
      one-armed and two-armed repressor-leucine zipper heterodimers shows that the
      subunit containing the arm in a one-armed repressor heterodimer binds
      preferentially in the consensus half-site of lambda operators. The patterns of
      activation of the P(RM) promoter in vivo by one-armed heterodimers containing the
      pc2 mutation in only one subunit show that RNA polymerase at P(RM) contacts the N
      terminal domain of the promoter-proximal subunit of the repressor dimer.

PMID- 9282744
TI  - Identification of novel chromosomal loci affecting Yersinia enterocolitica
      pathogenesis.
AB  - Pathogenic species of the genus Yersinia have a marked tropism for lymphoid
      tissue during the early stages of infection. Bacterial survival at this site
      determines whether the disease is localized or progresses systemically, leading
      to a high rate of mortality. Several plasmid-encoded virulence genes are known to
      be required for survival and pathogenesis, but the contribution of chromosomal
      genes has been largely unexplored. This study represents the first intensive
      effort to characterize and determine the function of Yersinia chromosomal genes
      expressed in lymphoid tissue after intragastric infection. Strains harbouring cat
      fusions expressed in the host were isolated from Peyer's patch tissue of mice
      intragastrically infected and treated with chloramphenicol (Cm); genes identified
      in this manner were designated hre for host responsive element. The hre::cat
      strains that were Cm resistant in vivo (in mouse tissue) and Cm sensitive in
      vitro (on laboratory media at 26 degrees C) were identified and shown to consist
      of 61 different allelic groups. The hre::cat fusions from 48 of the allelic
      groups were cloned and characterized by DNA sequence analysis. The results
      identified genes necessary for iron acquisition, protection from environmental
      stresses, biosynthesis of cell envelope components and other diverse metabolic
      activities. However, the DNA sequence of many clones had no homology to other
      known genes. Insertion mutations were constructed for four hre genes and the
      resulting Y. enterocolitica mutants were tested in the mouse model for effects on
      pathogenesis. All of the mutant strains were affected for virulence when assayed
      for survival in host tissues and LD50 analysis.

PMID- 9282745
TI  - Transcriptional analysis of the Streptococcus mutans hrcA, grpE and dnaK genes
      and regulation of expression in response to heat shock and environmental
      acidification.
AB  - The dental pathogen Streptococcus mutans persists and causes diseases in highly
      dynamic environments and gains a selective ecological advantage in environmental
      conditions that frequently exceed the limits for growth of the organism,
      particularly with regard to environmental pH. The goal of this study was to begin
      a molecular genetic analysis of a major stress protein, DnaK/Hsp70, to begin to
      understand how stress responses are regulated in this lactic acid bacterium and
      to establish a relationship between dnaK gene expression and exposure to acidic
      environments. Cloning and nucleotide sequence analysis revealed that the dnaK
      gene is preceded by, and is in an operon-like arrangement with, the hrcA and grpE
      genes, although intergenic spacing was unlike that described in other bacteria.
      An inverted repeat (a CIRCE element) was identified by sequence analysis and,
      using primer extensions, a heat shock-responsive, sigmaA-type promoter, P1, 5' to
      the hrcA gene, and a sigmaB-type promoter, 5' to the grpE translational start
      site, were identified. No promoters were detected between grpE and dnaK. A strain
      carrying a strongly polar insertion in the hrcA gene had markedly diminished
      levels of dnaK mRNA, indicating that dnaK was transcribed as part of an operon
      from P1, and to a lesser extent from P2. Results from physiological manipulation
      of S. mutans in continuous chemostat culture demonstrated that steadystate levels
      of S. mutans dnaK mRNA and DnaK protein were (i) increased in response to acid
      shock; (ii) elevated in acid 'adapted' cells; and (iii) induced in response to
      alkali shock of acid 'adapted' cells. In all cases, increased amounts of dnaK
      mRNA could be correlated with enhanced transcription from P1. This study provides
      the first detailed analysis of the expression of a heat shock gene from an oral
      isolate, and the evidence provided suggests that sigmaB-like promoters may also
      be involved in class I heat shock gene expression in some Gram-positive
      organisms.

PMID- 9282746
TI  - The erythrocyte receptor for the channel-forming toxin aerolysin is a novel
      glycosylphosphatidylinositol-anchored protein.
AB  - The plasma membrane of rat erythrocytes contains a 47-kDa glycoprotein that binds
      the channel-forming toxin aerolysin with high affinity and accounts for the
      sensitivity of these cells to the toxin. The receptor was purified so that its N
      terminal sequence could be determined after Western blotting. The sequence did
      not match any sequences in the databases, indicating that the receptor is a novel
      erythrocyte surface protein. However, it exhibited considerable homology to the N
      termini of a group of membrane proteins that are thought to be involved in ADP
      ribosyl transfer reactions. A common property of these proteins is that they are
      attached to plasma membranes by C-terminal glycosylphosphatidylinositol (GPI)
      anchors. The aerolysin receptor was shown to be anchored in the same way by
      treating rat erythrocytes with phosphatidylinositol-specific phospholipase C.
      This caused the selective release of the receptor and a reduction in the rodent
      cells' sensitivity to aerolysin. Human and bovine erythrocytes were shown to
      contain an aerolysin-binding protein with similar properties to the rat
      erythrocyte receptor. Proteins with GPI anchors are thought to have unusually
      high lateral mobility, and this may be an advantage for a toxin, such as
      aerolysin, which must oligomerize after binding to become insertion competent.

PMID- 9282747
TI  - Type III secretion genes identify a putative virulence locus of Chlamydia.
AB  - Four genes of Chlamydia psittaci strain guinea pig inclusion conjunctivitis
      (GPIC), whose predicted products are highly homologous to structural and
      regulatory components of a contact-dependent or type III secretion apparatus,
      were isolated. Related to genes present in several animal and plant bacterial
      pathogens, these genes may represent a section of a previously undetected
      chromosomal virulence locus analogous to several recently described virulence
      associated type III secretion loci. The existence of contact-dependent secretion
      in Chlamydia strongly suggests that these bacteria use pathogenic mechanisms that
      are similar to those of other intracellular bacterial pathogens. Unlike other
      intracellular bacteria, however, chlamydiae are metabolically inactive
      extracellularly and only become capable of global protein synthesis several hours
      after infection. This implies that chlamydial contact-dependent secretion is only
      active from within, uniquely after the bacteria have been internalized by
      eukaryotic cells. The possible role(s) of this pathway in chlamydial pathogenesis
      are discussed.

PMID- 9282748
TI  - The Borrelia burgdorferi circular plasmid cp26: conservation of plasmid structure
      and targeted inactivation of the ospC gene.
AB  - The 26 to 28kb circular plasmid of B. burgdorferi sensu lato (cp26) is ubiquitous
      among bacteria of this group and contains loci implicated in the mouse-tick
      transmission cycle. Restriction mapping and Southern hybridization indicated that
      the structure of cp26 is conserved among isolates from different origins and
      culture passage histories. The cp26 ospC gene encodes an outer surface protein
      whose synthesis within infected ticks increases when the ticks feed, and whose
      synthesis in culture increases after a temperature upshift. Previous studies of
      ospC coding sequences showed them to have stretches of sequence apparently
      derived from the ospC genes of distantly related isolates by homologous
      recombination after DNA transfer. We found conservation of the promoter regions
      of the ospC and guaA genes, which are divergently transcribed. We also
      demonstrated that the increase in OspC protein after a temperature upshift
      parallels increases in mRNA levels, as expected if regulatory regions adjoin the
      conserved sequences in the promoter regions. Finally, we used directed insertion
      to inactivate the ospC gene of a non-infectious isolate. This first example of
      directed gene inactivation in B. burgdorferi shows that the OspC protein is not
      required for stable maintenance of cp26 or growth in culture.

PMID- 9282749
TI  - Inactivation of the 20S proteasome in Mycobacterium smegmatis.
AB  - The 20S proteasome is an essential component of the cytosolic protein turnover
      apparatus of eukaryotic cells. In higher eukaryotes, the 20S proteasome is
      responsible for most cytosolic protein turnover and also generates peptides for
      subsequent presentation by the MHC class I pathway. Structurally, the eukaryotic
      20S proteasome is extremely complex, being composed of 14 different subunits.
      Proteasomes with simplified subunit composition have been identified in certain
      eubacteria and archaebacteria but, in each case, the proteasome-containing
      organism is recalcitrant to further molecular genetic analyses. As a result, no
      in vivo characterization of a simplified eubacterial or archaebacterial
      proteasome has been reported. We have shown that the genetically tractable
      eubacterium Mycobacterium smegmatis contains a 20S proteasome, allowing the first
      in vivo characterization of a simplified 20S proteasome. We use a
      positive/negative selection scheme to inactivate the genes encoding 20S
      proteasome subunits and demonstrate that, in contrast to eukaryotic cells, M.
      smegmatis cells lacking intact proteasome genes are viable and phenotypically
      indistinguishable from congenic strains containing proteasomes. Implications for
      the evolution of the protein turnover apparatus are discussed.

PMID- 9282750
TI  - The highly thermostable arginine repressor of Bacillus stearothermophilus: gene
      cloning and repressor-operator interactions.
AB  - We report here the cloning of the arginine repressor gene argR of Bacillus
      stearothermophilus and the characterization and purification to homogeneity of
      its product. The deduced amino acid sequence of the 16.8-kDa ArgR subunit shares
      72% identity with its mesophilic homologue AhrC of Bacilus subtilis. Sequence
      analysis of B. stearothermophilus ArgR and comparisons with mesophilic arginine
      repressors suggest that the thermostable repressor comprises an N-terminal DNA
      binding and a C-terminal oligomerization and arginine-binding region. B.
      stearothermophilus ArgR has been overexpressed in E. coli and purified as a 48.0
      kDa trimeric protein. The repressor inhibits the expression of a B.
      stearothermophilus argC-lacZ fusion in E. coli cells. In the presence of
      arginine, the purified protein binds tightly and specifically to the argC
      operator, which largely overlaps the argC promoter. The purified B.
      stearothermophilus repressor proved to be very thermostable with a half-life of
      approximately 30 min at 90 degrees C, whereas B. subtilis AhrC was largely
      inactivated at 65 degrees C. Moreover, ArgR operator complexes were found to be
      remarkably thermostable and could be formed efficiently at up to 85 degrees C,
      well above the optimal growth temperature of the moderate thermophile B.
      stearothermophilus. This pronounced resistance of the repressor-operator
      complexes to heat treatment suggests that the same type of regulatory mechanism
      could operate in extreme thermophiles.

PMID- 9282751
TI  - Copper-dependent reciprocal transcriptional regulation of methane monooxygenase
      genes in Methylococcus capsulatus and Methylosinus trichosporium.
AB  - The methanotrophic bacteria Methylococcus capsulatus (Bath) and Methylosinus
      trichosporium OB3b convert methane to methanol using the enzyme, methane
      monooxygenase (MMO). These bacteria are able to express two distinct MMOs: a
      cytoplasmic or soluble form (sMMO) and a membrane-bound or particulate form
      (pMMO). Differential expression of sMMO and pMMO is regulated by the amount of
      copper ions available to the cells; sMMO is expressed at low copper-biomass
      ratios, whereas pMMO is expressed at high copper-biomass ratios. In both
      methanotrophs, transcription of the sMMO gene cluster is negatively regulated by
      copper ions. Data suggest that transcription of the M. trichosporium OB3b sMMO
      gene cluster is directed from a sigma54-like and a sigma70-like promoter. The
      pMMO (pmo) genes of M. capsulatus (Bath) are transcribed into a polycistronic
      mRNA of 3.3 kb. The synthesis of this mRNA was activated by copper ions.
      Activation of pmo transcription by copper ions was concomitant with repression of
      sMMO gene transcription in both methanotrophs. This suggests that a common
      regulatory pathway may be involved in the transcriptional switch between sMMO and
      pMMO gene expression.

PMID- 9282752
TI  - Analysis of cis-acting sequence and structural elements required for
      antitermination of the Bacillus subtilis tyrS gene.
AB  - The Bacillus subtilis tyrS gene belongs to the T box family of aminoacyl-tRNA
      synthetase and amino acid biosynthesis genes, which are regulated by a common
      mechanism of transcriptional antitermination. Each gene is induced by specific
      amino acid limitation; the uncharged cognate tRNA is the effector inducing
      transcription of the full-length message. The leader regions of the genes in this
      family share a number of conserved primary sequence and secondary structural
      elements, the functions of which are unknown. In this study, we examine these
      regions and report the effects of mutations in several of these elements. In
      addition, two alternative basepairings in the F box region were found to be
      necessary for tyrS antitermination.

PMID- 9282753
TI  - Coiled-coil domains in proteins secreted by type III secretion systems.

PMID- 9282755
TI  - Experimental technique for (laparoscopic) bowel anastomosis: transient
      endoluminally stented anastomosis (TESA).
AB  - A new technique for bowel anastomosis is presented. The principle of transient
      endoluminally stented anastomosis (TESA) is based on anastomosing the two bowel
      ends around a resorbable stent of polyglycolic acid (PGA) in seroserosal contact.
      To evaluate the feasibility of TESA for bowel anastomosis, laparoscopic colon
      anastomosis following sigma resection was performed in five juvenile pigs. Three
      animals were sacrificed 2 months postoperatively, and the anastomoses were
      examined radiologically and histologically. One animal was sacrificed at day 2,
      suffering from acute peritonitis due to small bowel leak but with regular colon
      anastomosis. One trial was terminated at the fourth postoperative day because of
      insufficiency of the colon anastomosis. Three animals did not have any
      complications during the 2-month follow-up. In these animals the colon
      anastomoses were not detectable radiologically at the time of death. The
      microscopic examination showed intact mucosal and muscular layers without foreign
      material. Our study demonstrates that laparoscopic application of TESA to colon
      anastomosis is a feasible method. These results will further stimulate our future
      research for an anastomosis technique avoiding remnant foreign material.

PMID- 9282754
TI  - Laparoscopic adrenalectomy: comparison with the conventional approach.
AB  - Laparoscopic adrenalectomy (LA) was performed on 14 patients with adrenal tumors.
      Herein we describe the laparoscopic procedure and the patients' clinical course
      compared with those of patients who underwent the conventional posterior or
      transabdominal approach (PA, TA). The 14 patients included four men and 10 women
      aged 28 to 69 years. Clinical diagnoses in this series were primary aldosteronism
      in seven patients, Cushing's adenoma in four patients, and nonfunctioning tumor
      in three patients. Maximum diameters of the adrenal tumors ranged from 10 to 48
      mm. In all patients, the adrenal tumors were removed successfully. The mean
      operating time was longer for LA- than for PA- or TA-treated patients (185 versus
      99 and 143 min), whereas the mean blood loss was smaller for LA- or PA-treated
      (92 and 126 ml) than for TA-treated patients (407 ml). The patients'
      postoperative condition, as assessed in terms of the number of febrile days,
      leucocytosis, and elevation of C-reactive protein value, was significantly better
      with LA. In addition, the frequency of administration of analgesics was lower and
      the time required until the patient could walk were shorter after LA than after
      PA and TA. In conclusion, laparoscopic adrenalectomy appears to be a minimally
      invasive and safe therapeutic option that may become a standard procedure for
      adrenal surgery.

PMID- 9282756
TI  - Minimally invasive tube gastrostomy.
AB  - With the increasing use of surgically placed enteral feeding tubes, we have seen
      a marked increase in the number of complications related to the tubes and their
      management. This has resulted in an increase in returns to emergency departments,
      readmissions to hospitals, and returns to the operating room. This, in turn, has
      led to a dramatic increase in the cost to society for the aftercare of the
      feeding tubes. This article describes a technique designed to reduce
      complications and revisits to hospitals, while at the same time allowing greater
      flexibility and ease of management in patients who require long-term enteral
      feeding.

PMID- 9282757
TI  - Intestinal obstruction after laparoscopic herniorrhaphy.
AB  - Laparoscopic herniorrhaphy is still a controversial procedure. Two cases of
      intestinal obstruction after laparoscopic herniorrhaphy are reported. The
      clinical features, possible mechanisms, managements, and outcomes were analyzed.
      The results showed that preexisting mesenteric defect, fibrin depositions, and
      longer operation time were predisposing factors for post-laparoscopic
      herniorrhaphy intestinal obstruction. These findings suggest that cleansing of
      fibrin deposition and shorter operation times may be important to avoid
      postoperative intestinal obstruction.

PMID- 9282758
TI  - Giant omental cyst in children presenting as pseudoascites.
AB  - An unusual case of omental cyst is described. During a period of 3 years, a child
      was hospitalized seven times in five different hospitals for evaluation of
      ascites of unknown origin. Extensive and repetitive diagnostic workup did not
      reveal the cause of his problem, and recurrent paracentesis improved his
      condition partially, but for very short periods. A diagnostic laparoscopy,
      followed by explorative laparotomy, led to the correct diagnosis and appropriate
      surgical treatment, with complete relief of his complaints.

PMID- 9282759
TI  - Laparoscopic Roux-en-Y gastric bypass for morbid obesity: a feasibility study in
      pigs.
AB  - According to randomized prospective studies in humans, the Roux-en-Y gastric
      bypass provides more effective weight loss than vertical banded gastroplasty for
      morbid obesity. Ten pigs underwent laparoscopic Roux-en-Y gastric bypass to
      assess the feasibility of this procedure with conventional laparoscopic
      techniques and instruments. The procedure took an average of 4 h 20 min. Of the
      first five pigs killed immediately, four had correct anastomoses. Of the five
      remaining pigs with postoperative follow-up, three survived with an intact
      anastomosis and staple line at autopsy. Two died within 48 h, one from
      peritonitis (perforation of the small bowel), the other from unknown causes. A
      definite learning curve exists for this procedure primarily because of the extent
      of gastrointestinal reconstruction, but there is potential for it to be used in
      humans.

PMID- 9282761
TI  - Video thoracoscopic resection of neurogenic tumor in a superior-posterior
      mediastinum: three case reports.
AB  - Neurogenic tumors of the thorax can originate in any neurogenic structure within
      the chest. Surgical resection is considered the primary treatment of such tumors
      and usually is performed through a thoracotomy. Recently, using a new approach,
      we applied the technique of video thoracoscopic surgery to resection a posterior
      mediastinal tumor. In this paper, we report three patients with superior
      posterior mediastinal neurogenic tumors in which the approach to the tumor is
      technically difficult. Cases 1 and 2 were a 26-year-old man and a 50-year-old
      asymptomatic man, respectively, and case 3 was a 45-year-old asymptomatic woman.
      The sizes of the three tumors were 3.0 x 2.5 x 1.8 cm (case 1), 6.0 x 4.0 x 2.0
      cm (case 2), and 3.0 x 2.0 x 2.0 cm (case 3). In one case (case 2),
      minithoracotomy was added to video thoracoscopic surgery for adhesion to the
      spinal artery and intraspinal extension. A standard thoracotomy was avoided in
      all three cases. All patients had uncomplicated postoperative courses. Video
      thoracoscopic resection of a neurogenic tumor in the superior-posterior
      mediastinum may be a safe and useful approach with improved cosmetic results.

PMID- 9282760
TI  - Laparoscopically treated duodenal hamartoma of Brunner's glands.
AB  - Hamartomas of Brunner's glands are extremely rare lesions, with only about 100
      cases reported to date in the world literature; of these, fewer than 25
      correspond to growths >2 cm in diameter. We report the case of a patient with a
      large (6-cm diameter) duodenal hamartoma of Brunner's glands treated by
      laparoscopic surgery. A review of the literature revealed no other cases via this
      approach.

PMID- 9282762
TI  - Endoscopic retroperitoneal right adrenalectomy with the patient in the lateral
      decubitus position.
AB  - We present a case of a right adrenal aldosterone-producing adenoma resected by a
      novel surgical approach. We describe the technique of an endoscopic
      retroperitoneal adrenalectomy done with the patient in the lateral decubitus
      position.

PMID- 9282763
TI  - Correlation among ultrasonographic and videoscopic findings of the gallbladder:
      surgical difficulties and reasons for conversion during laparoscopic surgery.
AB  - Laparoscopic cholecystectomy is currently the standard procedure for chronic and
      acute cholecystitis. The purpose of this prospective study was to evaluate the
      preoperative ultrasound findings of the gallbladder and correlate those aspects
      with surgical videoscopic and histopathologic findings and the results concerning
      intraoperative complications and the conversion index to open surgery.
      Gallbladder findings were classified into three categories according to the
      gallbladder wall characteristics and the presence of visible lumen and stones.
      Simple chronic cholecystitis (type I) and acute cholecystitis, with gallbladder
      wall thickness <5 mm (type IIa) presented significantly lower intraoperative
      complications without conversion to open surgery. Scleroatrophic (type III) and
      acute cholecystitis with gallbladder wall thickness >5 mm (type IIB) presented
      significantly more surgical difficulties and a higher conversion rate to open
      surgery (p < 0.01). We postulate that this classification will be useful for
      surgeons in predicting potential problems in individual patients, at least at the
      initial laparoscopic cholecystectomy experience, and in advising patients of the
      potential risks of and conversion to open surgery.

PMID- 9282764
TI  - An animal model for teaching subfacial ligation of perforator veins to treat
      venous stasis ulcers.
AB  - Endoscopic subfacial ligation of perforator veins in the lower limb has been
      described in the treatment of venous stasis ulcer. An animal model to enable
      surgeons to become familiar with the surgical technique is presented. The model
      uses the porcine abdominal wall and allows practice in endoscopic dissection and
      ligation using appropriate instrumentation in an environment that is a reasonable
      surrogate for the human calf.

PMID- 9282765
TI  - Laparoscopic pericardial window.
AB  - The creation of a drainage orifice in the pericardium for the release of an
      accumulated effusion has been proven to be an effective means to eliminate the
      physiologic effects of a cardiac tamponade. Numerous surgical approaches have
      been used to create an opening in the pericardium for this purpose. Thoracic and
      thoracoscopic approaches have been found to produce a fair amount of morbidity by
      further compromising an already compromised cardiopulmonary system by
      necessitating an invasion into the hemithorax and the requirement of a
      thoracostomy tube. This report identifies a laparoscopic technique for the
      creation of a pericardial window with low morbidity that has been successfully
      used in 14 patients who presented to the Department of Surgery of the Rapid City
      Medical Center with clinical evidence of pericardial effusion and tamponade.

PMID- 9282766
TI  - Incidence of thromboembolic complications after laparoscopic cholecystectomy:
      review of the literature.
AB  - The purpose of this study was to quantify the risk of thromboembolic
      complications after laparoscopic cholecystectomy by a survey of the literature.
      We reviewed 60 laparoscopic cholecystectomy series consisting of 153,832
      patients. The average mortality was 0.08%. The average rate of fatal pulmonary
      embolism was 0.02% and total pulmonary embolism 0.06%. The average rate of
      reported deep vein thrombosis was 0.03%. We conclude that laparoscopic
      cholecystectomy is a safe procedure, and the rate of clinically evident
      postoperative thromboembolic complications is probably lower than after
      conventional cholecystectomy. A lingering bias due to the overrepresentation of
      young and healthy patients early in the era of laparoscopic cholecystectomy
      could, however, still affect these figures. An underreporting of the lesser
      complications is likely. The risk is not negligible, though, and some authors
      have recommended thromboembolism prophylaxis, although further studies are
      necessary to find the optimal prophylaxis strategy. The true incidence is
      possible to establish only by using objective diagnostic methods for
      surveillance.

PMID- 9282767
TI  - Pneumoperitoneum: its alternatives.
AB  - The purpose of this study was to determine the advantages and disadvantages of
      several techniques for performing the pneumoperitoneum. We studied 75 patients
      divided into three groups of 25 each. In the first group, we used the Veress
      needle technique in the umbilicus. In the second group, the insertion was in the
      upper left quadrant, and in the third group the insertion was direct with a
      disposable trocar in the umbilicus without pneumoperitoneum. In the first group,
      we made 32 attempts, and the time varied from 8 to 35 min. In the second group we
      made 28 attempts and the time was from 3 to 6 min. In both we had complications.
      In the third group, we made 25 direct insertions without complications, and the
      time was from 45 s to 3 min.

PMID- 9282768
TI  - Laparoscopic versus open appendectomy: a prospective randomized trial.
AB  - To study comparative results between laparoscopic and open appendectomy, all the
      patients with suspected acute appendicitis who presented between January 1992 and
      December 1994 (N = 210) were randomized into two groups: laparoscopic (LA, n =
      106) and open appendectomy (OA, n = 104). Patient demographics, pathological
      findings, operative time, postoperative course, and cost were analyzed. Age,
      gender, previous laparotomy, intraoperative diagnosis, and perforated appendix
      rate were comparable between both groups. Mean operative time was longer in the
      LA group (p < 0.05). Earlier resumption of a regular diet, shorter postoperative
      stay, and less postoperative analgesia also were observed in the LA group (p <
      0.05). Postoperative morbidity and hospital readmissions were similar in both
      groups (p > 0.05). Higher operative cost was observed in the LA group, but global
      cost was lower in this group (p < 0.05). Laparoscopic appendectomy shows a more
      comfortable postoperative course (oral resumption, postoperative stay, and
      analgesia) over open appendectomy, with similar postoperative morbidity. The LA
      group showed more operative but less global cost.

PMID- 9282769
TI  - Laparoscopic accessory splenectomy for recurrent idiopathic thrombocytopenic
      purpura.
AB  - This report describes the use of laparoscopic accessory splenectomy in treating
      recurrent idiopathic thrombocytopenic purpura (ITP). The patient presented 36
      months after initial splenectomy with a platelet count of 16,000 cells/microl and
      nontolerance of medical therapy. A technetium-99 labeled, heat-damaged red blood
      cell scan revealed two small foci in the upper left quadrant. This finding was
      confirmed by an abdominal computed tomography scan. After laparoscopic accessory
      splenectomy, the patient was discharged (23 h after surgery) and at 9 months
      showed a platelet count of 234,000 cells/microl with no medical therapy. A
      minimally invasive approach to accessory spleen removal can be beneficial to
      patients with recurrent ITP and documented accessory splenic tissue.

PMID- 9282770
TI  - Trocar incision and closure: daily problems in laparoscopic procedures--a new
      technical aspect.
AB  - A mini-laparotomy as described by Hasson was used in a modified way in 1,500
      laparoscopic procedures. In comparison with the insertion of a Veress needle, we
      find the open approach to be a safer and quicker technique to obtain the
      pneumoperitoneum. A new technique for closure of the trocar incision is
      described. The technique is recommended due to its easy and safe approach
      requiring no additional special equipment.

PMID- 9282771
TI  - Laparoscopic management of small bowel obstruction caused by a retrocaecal
      hernia.
AB  - Laparoscopy is not commonly used in the management of small bowel obstruction
      (SBO). We report the first documented case of laparoscopic diagnosis and
      treatment of a retrocaecal hernia, a type of internal abdominal hernia. An 86
      year-old woman with a chest infection was referred with features of a well
      established SBO. At laparoscopy, the hernia was quickly diagnosed and easily
      reduced, the bowel assessed for viability, and the sac treated by widely laying
      open its neck, thereby marsupializing the defect. A laparotomy was avoided, and
      she recovered promptly and without complication. We conclude that laparoscopy can
      play a useful role in the management of SBO and that its use should be considered
      in patients with no obvious external hernia and a virgin abdomen in whom an
      unusual cause is suspected.

PMID- 9282772
TI  - Transthoracic percutaneous endoscopic gastrostomy (PEG) after esophagectomy and
      gastric pull-up.
AB  - The technique of transthoracic percutaneous endoscopic gastrostomy (PEG) tube
      placement is described as an alternative to standard nasogastric tube drainage
      and inpatient observation for those patients who require gastric decompression
      after esophagectomy with gastric pull-up. Indications for transthoracic PEG tube
      insertion are distention and poor emptying of the intrathoracic stomach conduit
      with or without contained anastomotic leak, especially when it appears as if the
      problem will be slow to resolve. This technique is not advocated for patients
      with free anastomotic leaks. The potential advantages of this technique over
      standard nasogastric drainage are that it permits stable patients to be treated
      successfully as outpatients.

PMID- 9282774
TI  - Stump appendicitis--a potential problem after laparoscopic appendicectomy.
AB  - Appendicitis is now commonly diagnosed and treated using laparoscopic techniques.
      Laparoscopic appendicectomy has the potential to result in incomplete removal of
      the appendix stump and subsequent risk of stump appendicitis. This article
      reports such a case, requiring laparotomy 5 months after the original
      appendectomy.

PMID- 9282773
TI  - Laparoscopic pylorus-preserving gastrectomy with intracorporeal hand-sewn
      anastomosis.
AB  - To prevent stapled stenosis after laparoscopic local gastric resection by using
      autosuturing devices, we developed a technique for laparoscopic pylorus
      preserving gastrectomy with intracorporeal hand-sewn anastomosis. We describe
      this procedure and present two case reports. The intracorporeal hand-sewn
      anastomotic technique is an important advance in the field of minimally invasive
      laparoscopic surgery.

PMID- 9282775
TI  - Endoscopic removal of nasogastric tube sutured unintentionally to
      gastrojejunostomy.
AB  - A nasogastric tube mistakenly sutured to the anastomotic site is a rare surgical
      error during gastrointestinal operation. When it does happen, proper management
      will prevent subsequent complications. If resistance is experienced when pulling
      the nasogastric tube after gastrointestinal surgery, it should never be pulled
      more forcefully. The endoscope should be introduced to document the etiology and
      to provide treatment after 2 weeks postoperation based on the wound healing
      process and strength of suture materials.

PMID- 9282776
TI  - Antigenic features of foot-and-mouth disease virus serotype Asia1 as revealed by
      monoclonal antibodies and neutralization-escape mutants.
AB  - Neutralizable antigenic sites/epitopes of serotype Asial foot-and-mouth disease
      virus (strain IND63/72) were identified using monoclonal antibodies (mabs) and
      their neutralization-escape mutants. Relative affinity/reactivity of the mabs for
      viral (both native and trypsin-cleaved) and subviral antigens in enzyme-linked
      immunosorbent assay (ELISA) showed dominance of trypsin-sensitive and
      conformation-dependent neutralizable antigenic sites. Characterization of
      neutralization escape mutants identified at least four independent trypsin
      sensitive neutralizable antigenic sites on Asial FMD virus. One site was
      identified by mabs B3, 1A, 24, 2A, 40 and 63, second site by mabs 34 and 81,
      third site by mab 72 and fourth site by mab 89. The reaction profile of the mabs
      with selected field isolates in ELISA identified four different neutralization
      epitopes within the site B3/1A/24/2A/40/63.

PMID- 9282778
TI  - Simian foamy virus type 1 (SFV-1) induces apoptosis.
AB  - Foamy virus infection causes cytopathology in several cell types from different
      species. The mechanism of cell killing by foamy viruses is not known. In this
      report, the mechanism of cell death induced by simian foamy virus type 1 (SFV-1)
      infection was investigated in fibroblast and lymphoid derived cells lines.
      Infected L-929 (fibroblast) and Raji (B cell) cells showed chromatin
      condensation, chromatin cleavage into nucleosome oligomers, and ultrastructural
      changes consistent with apoptosis. These data suggest that SFV-1 induced
      apoptotic cell death in different cell lines from different species. The degree
      of apoptotic cell death in both L-929 and Raji cell lines correlated with
      increased virus replication. Apoptosis, therefore, is one mechanism by which SFV
      1 causes cell death.

PMID- 9282777
TI  - Inhibition of HIV-1, HIV-2 and SIV envelope glycoprotein-mediated cell fusion by
      calmodulin.
AB  - Calmodulin, an EF-hand protein, inhibited the fusion between CD4+ human cells and
      cells stably expressing HIV-1 envelope proteins. Fusion was also inhibited when
      HIV-1, HIV-2 or SIV envelope glycoproteins were expressed by vaccinia virus (VV)
      recombinants, but calmodulin did not inhibit syncytia formation induced by
      measles virus glycoproteins. Calmodulin also inhibited fusion induced by vPE17, a
      VV-recombinant expressing a truncated form of HIV-1gp160 which lacks the two
      known calmodulin-binding sites located in the cytoplasmic domain of gp41. The
      inhibitory activity was specific to calmodulin among the EF-hand proteins. These
      observations may be important in understanding the mechanism of retroviral
      envelope glycoprotein-mediated cell fusion. Several possible mechanisms of action
      are discussed.

PMID- 9282779
TI  - Antigenic variation of the Epstein-Barr virus nuclear antigen EBNA1 as revealed
      by monoclonal antibodies.
AB  - The Epstein Barr virus (EBV) nuclear antigen EBNA1 plays an essential role in the
      replication of EBV episomes in latently infected cells and is the only viral
      protein that is consistently expressed in all programs of latent EBV gene
      expression. In this study, four monoclonal antibodies (MoAbs) directed to a
      region (amino acid residues 442-530) of EBNA1 were generated. Competitive enzyme
      linked immunosorbent assay (ELISA) experiments using biotinylated MoAbs showed
      that they recognized distinct epitopes. Reactivity of these MoAbs with various
      laboratory EBV strains and field EBV isolates was shown to be heterogeneous in
      that EBNA1 from certain strains (isolates) was recognized and that from others
      was not. All four MoAbs showed such heterogeneous reactivity, and moreover, each
      MoAb showed a distinct spectrum of reactivity with these EBV strains (isolates).
      These results demonstrate an extensive structural variation in this region of
      EBNA1 as predicted by previous sequencing studies. These MoAbs will be useful as
      probes to dissect this structural heterogeneity of EBNA1.

PMID- 9282780
TI  - Identification and sequence analysis of the integration site of transposon TCp3.2
      in the genome of Cydia pomonella granulovirus.
AB  - Recently, we described the isolation and characterisation of the novel
      lepidopteran transposon TCp3.2, which was found to be inserted into the genome of
      a spontaneous mutant of the baculovirus Cydia pomonella granulovirus (CpGV).
      Transposon TCp3.2, which is a member of the Tcl/mariner superfamily, is an
      apparently defective copy which became stably integrated into the viral genome
      (Jehle et al., 1997. J. Mol. Evol., in press). In this study, we located, cloned
      and sequenced a genomic region of 2.5 kb of CpGV which encompasses the insertion
      site of TCp3.2. The TCp3.2 was inserted at a TA dinucleotide as it is typical for
      many Tcl/mariner-like transposons. The TA insertion site was localised within a
      non-translated region downstream of the homologous gene of baculovirus late
      expression factor 2 (lef-2). Additionally, three other complete open reading
      frames (ORF35Ra, ORF35Rb, and ORF36L) with unknown functions were identified.
      Transposon insertion into intergenic regions of viral genomes may contribute to
      the genotypic variability of baculoviruses without any phenotypic effect.

PMID- 9282781
TI  - High level expression of equine herpesvirus 1 glycoproteins D and H and their
      role in protection against virus challenge in the C3H (H-2Kk) murine model.
AB  - N and C-terminal truncated forms of equine herpesvirus 1 (EHV 1) glycoproteins gD
      and gH were expressed in baculovirus resulting in the production of secreted
      recombinant proteins. A carboxy-terminal histidine tag was included on each of
      the genes for protein isolation by nickel affinity chromatography. Recombinant gD
      was recognized by three gD specific monoclonal antibodies, 20C4, 5H6 and F3132.
      F3132 is a conformationally dependent monoclonal antibody with virus neutralizing
      activity. Expression of gH was confirmed by reacting the protein with the gH
      peptide specific antiserum R319. The truncated gD gene was also expressed as a
      beta-galactosidase fusion protein which was purified from E. coli by nickel
      affinity chromatography. C3H mice were inoculated with purified recombinant gD or
      gH or insect cells which had been infected with recombinant baculoviruses. Mice
      were subsequently challenged with EHV 1. Purified recombinant baculovirus gD
      provided the most protection and produced high levels of virus neutralizing
      antibodies. The gD fusion protein was less effective at protecting mice and
      insect cells infected with either of the recombinant baculoviruses or purified
      recombinant gH were poor at conferring protection. The results emphasize the
      importance of using purified proteins in vaccine formulations and of including
      EHV 1 gD as a component of a subunit vaccine.

PMID- 9282782
TI  - Complete RNA1 sequences of two UK isolates of barley mild mosaic virus: a wild
      type fungus-transmissible isolate and a non-fungus-transmissible derivative.
AB  - The complete RNA1 sequences of two isolates (fungus transmissible and non-fungus
      transmissible) of barley mild mosaic virus (BaMMV) were obtained. The two
      isolates' RNA1 sequences had very high sequence identity (99.3%), and of the 15
      amino acid differences (out of 2258) between the putative polyproteins, 11 were
      conservative and unlikely to affect the structure or function of the protein. The
      remaining amino acid differences were thought unlikely to affect fungus
      transmission because they occur in the CI- and NIb-coding regions. This strongly
      suggests that the P73 protein of RNA2 (which has a 364-aa deletion in the non
      fungus-transmissible isolate) is involved in fungus transmission of BaMMV.

PMID- 9282783
TI  - Peptide-specific CTL induction in HBV-seropositive PBMC by stimulation with
      peptides in vitro: novel epitopes identified from chronic carriers.
AB  - Cytotoxic T lymphocytes (CTL) recognize and destroy virus-infected cells, and it
      has been established that epitope-based peptides could induce such CTL in vivo as
      well as in vitro. In this study attempts were made to define the epitopes that
      are recognized by the CTL, and thus a series of 9- to 10-mer peptides derived
      from the amino acid sequences of hepatitis B virus (HBV) proteins were
      synthesized on the basis of the previously described HLA-A2 peptide binding
      motif. The binding assay of the synthetic peptides using transporter-associated
      with antigen processing (TAP)-deficient human cell line, T2, showed that eight
      out of 11 peptides tested enhanced the expression of HLA-A2 molecules on the T2
      cell surface. Some of these peptides triggered activation of CTL in peripheral
      blood mononuclear cells of HBV-seropositive chronic carriers. The activated CTL
      in turn recognized and killed the T2 cells pulsed with the same peptides. This
      study shows that novel HLA-A2-restricted epitopes exist in the natural repertoire
      of immunity against HBV. These findings can be useful in developing peptide-based
      therapeutics against viral infections.

PMID- 9282784
TI  - Repression of tumor necrosis factor-beta expression by the human immunodeficiency
      virus type-1 tat protein in central nervous system-derived glial cells.
AB  - HIV-1 Tat is a potent transactivator that stimulates expression from the HIV-1
      LTR, from certain cellular gene promoters and from several heterologous viral
      promoters. Previous reports show that HIV-1 Tat transactivates tumor necrosis
      factor-beta (TNF-beta) promoter-directed gene expression in lymphocytic and
      monocytic cell lines and further demonstrate that a 'TAR-like structure'
      downstream of the TNF-beta promoter is essential for Tat activity. The ability of
      Tat to activate TNF-beta may have profound effects as TNF has been shown to be a
      potent activator of HIV-1 gene expression and an important immunomodulatory and
      growth regulatory factor. The studies presented herein demonstrate a novel
      finding where HIV-1 Tat specifically represses (> 10-fold) TNF-beta promoter
      directed gene expression in central nervous system-derived glial cells. Amino
      acid residues 2 to 36 of HIV-1 Tat are required for TNF-beta repression. Tat
      repression of TNF-beta, a factor which upregulates HIV-1 gene expression,
      suggests a novel mechanism whereby HIV-1 is able to establish latent infection of
      glial cells that present no detectable virions and/or viral antigens.

PMID- 9282785
TI  - Antigenic and genetic comparisons of Japanese and Australian Simbu serogroup
      viruses: evidence for the recovery of natural virus reassortants.
AB  - The antigenicity and RNA genome structures of five Simbu serogroup bunyaviruses
      isolated in Japan and Australia were analyzed using monoclonal antibodies (Mabs)
      raised to Akabane (AKA) virus and oligonucleotide fingerprinting. The virion
      surface glycoprotein (G1) and the nucleocapsid (N) protein of heterologous
      viruses showed no reactivity to the Mabs, while the AKA-derived anti-G1 Mab (2F1)
      reacted with Peaton virus and all three AKA anti-N Mabs reacted with Tinaroo
      (TIN) virus at almost the same antibody titers as the homologous virus.
      Oligonucleotide fingerprinting analyses indicated that the three RNA species of
      all the viruses were unique and distinguishable. However, AKA and TIN viruses
      exhibited very similar S RNA oligonucleotide fingerprints, while the L and M RNA
      fingerprints were quite different. The S RNA sequence of TIN virus has been
      determined and compared with that of AKA and Aino viruses. The results revealed
      95.1% S sequence homology between the AKA and TIN viruses. The antigenic and
      genetic comparisons of AKA and TIN viruses suggest that the two viruses may
      represent naturally occurring reassortant viruses.

PMID- 9282786
TI  - The fourth genus in the Orthomyxoviridae: sequence analyses of two Thogoto virus
      polymerase proteins and comparison with influenza viruses.
AB  - The tick-borne Thogoto virus (THOV) is the type species of a newly recognized
      fourth genus, Thogotovirus, in the family Orthomyxoviridae. Because of the
      distant relationship of THOV with the influenza viruses, determination of its
      genomic information can potentially be used to identify important domains in
      influenza virus proteins. We have determined the complete nucleotide sequence of
      the second longest RNA segment of THOV. The molecule comprises 2212 nucleotides
      with a single large open reading frame encoding a protein of 710 amino acids,
      estimated Mr 81,284. The protein shares 77% amino acid similarity with the PB1
      like protein of Dhori virus, a related tick-borne virus, and 50-53% with the PB1
      polymerase proteins of influenza virus A, B and C. All the motifs characteristic
      of RNA-dependent polymerases were identified including the SSDD motif common to
      all RNA-dependent RNA polymerases, indicating that the THOV protein is
      functionally analogous to the influenza virus PB1 proteins and involved in chain
      elongation. We also report the corrected sequence of the third longest RNA
      segment of THOV, encoding a protein which shares 44-47% amino acid similarity
      with the PA-like polymerase proteins of influenza virus A, B and C. The
      biological significance of conserved domains in these orthomyxovirid proteins is
      discussed.

PMID- 9282788
TI  - Comparison of the complete genomic sequence of the border disease virus, BD31, to
      other pestiviruses.
AB  - The genus Pestivirus is composed of hog cholera virus (HCV) [also known as
      classical swine fever virus (CSFV)], bovine viral diarrhea virus (BVDV), and
      border disease virus (BDV). Complete sequences have been published for HCV (or
      CSFV) and the two genotypes of BVDV (BVDV1 and BVDV2). In this study the complete
      sequence of the border disease virus (BDV), BD31, was determined. BD31 was
      isolated from a lamb with hairy shaker syndrome and is the BDV type virus offered
      by ATCC (ATCC VR-996). The genome was 12268 nucleotides long and had a single
      large open reading frame (ORF) beginning at nucleotide 357 and ending at
      nucleotide 12045. The sequence identity of the predicted amino acid sequence of
      BD31 and other published pestivirus sequences varied from 71% to 78%.
      Phylogenetic analysis of available complete genomic sequences segregated
      pestiviruses into two branches. One branch contained BD31 and HCV (or CSFV)
      isolates while the other branch contained BVDV1 and BVDV2 isolates. Pestiviruses
      from the same branch were similar in the length of the 5' and 3' untranslated
      regions (UTR). When complete genomic sequences were compared among BD31, HCV (or
      CSFV), BVDV1 and BVDV2, the highest sequence identity was observed in the 5' UTR.
      Within the ORF, the highest sequence identity was observed in the genomic region
      coding for the nonstructural viral polypeptide p80.

PMID- 9282787
TI  - Generation of an infectious cDNA of a highly cardiovirulent coxsackievirus
      B3(CVB3m) and comparison to other infectious CVB3 cDNAs.
AB  - An infectious cDNA of a highly myocarditic coxsackievirus B3 (CVB3m; Nancy
      strain) was cloned. Sequence data revealed 43 extra non-viral nucleotides
      upstream of the initial 5' sequence. However, the authentic 5' end sequence was
      maintained during replication of viral RNA transfected into HeLa cells,
      suggesting the RNA synthesizing complex edits the picornaviral 5' terminus
      sequence. Nucleotide sequences of the 5' nontranslated region and the capsid
      protein gene sequence of CVB3m were compared with the published sequences of five
      other CVB3 Nancy strains and two main lineages were found. In comparative assays
      for cardiovirulence, three of four CVB3 tested were cardiovirulent in adolescent
      male CD-1 mice. Only one of the three available CVB3 strains was neutralized with
      several anti-CVB3m monoclonal antibodies, suggesting that mutations in the
      surface epitopes of the capsid polypeptides contribute to antigenic drift within
      the serotype, perhaps in part through immunoselective pressures. Thus, phenotypic
      diversity of CVB3 within the prototype Nancy strain is an example of RNA viruses
      adapting to changing environments (cells, mice and humans) through mutations and
      selective pressure.

PMID- 9282789
TI  - Fibrinogen and fibrin polymerization: appraisal of the binding events that
      accompany fibrin generation and fibrin clot assembly.
AB  - Fibrinogen is a complex multifunctional protein comprised of three major domains
      (two outer D and one central E) which contains constitutive binding sites (e.g.
      Da, Db, gammaXL, D:D, gamma', thrombin substrate, platelet receptor) as well as
      binding sites that become exposed or expressed as a result of fibrinogen
      proteolysis by thrombin and/or that are exposed as a consequence of the
      polymerization process itself (tPA binding sites). Fibrin-dependent tPA-mediated
      activation of plasminogen is associated with exposure of polymerization-dependent
      epitopes (Aalpha148-160, gamma312-324) that are expressed in assembled fibrin and
      in crosslinked (polymerized) fibrinogen but not in unpolymerized fibrinogen or
      fibrin. Fibrin polymerization is initiated by thrombin cleavage of fibrinopeptide
      A from fibrinogen Aalpha chains, exposing two E domain E(A) sites. Cleavage of
      fibrinopeptide B from fibrinogen Bbeta chains exposes other E domain
      polymerization sites, termed E(B), that also interact with platelets, fibroblasts
      and endothelial cells. Fibrin generation is followed by an assembly process of
      intermolecular end-to-middle D to E associations to form linear and branched
      double-stranded fibrin fibrils, lateral fibril-fibril associations to form fibers
      and a branched fiber network. Binding sites in fibrinogen play their roles in
      fibrin assembly by self-association (gammaXL to gammaXL and D:D to D:D) or by
      complementary association with exposed sites in fibrin (Da to E(A) and Db to
      E[B]). Other binding sites in fibrinogen include thrombin substrate recognition
      sites in each E domain and a non-substrate high affinity thrombin binding site in
      the carboxy-terminal region of each gamma' chain, which also binds plasma factor
      XIII. Fibrin possesses low affinity thrombin binding sites in each E domain and
      retains the gamma' chain nonsubstrate thrombin-binding site.

PMID- 9282790
TI  - The use of two different APC resistance assay systems provides optimal
      sensitivity and specificity for diagnosing genetic APC resistance.
AB  - We compared the performance characteristics of a commercial dilute Russell's
      viper venom (DRVV)-based APC resistance assay (Gradipore PC Impedance Test) to a
      routinely utilized commercial APTT based assay (Coatest APC Resistance Assay).
      The DRVV based assay offers improved sensitivity and specificity for the factor V
      Leiden mutation. However, the routine use of both assays provides optimum
      reliability for diagnosis of genetic APC resistance. Our results suggest that
      when both tests are either positive or negative, DNA analysis is unnecessary.
      Interference by lupus anticoagulants is dramatically minimized by the
      phospholipid rich DRVV reagent used in the assay and it is insensitive to high
      factor VIII activity. Additionally, discrepant functional assay results allow
      identification of patients who may have an acquired APC resistant phenotype.

PMID- 9282791
TI  - The antithrombotic effects of recombinant human soluble thrombomodulin (rhsTM) on
      tissue factor-induced disseminated intravascular coagulation in crab-eating
      monkeys (Macaca fascicularis).
AB  - We evaluated the antithrombotic effects of recombinant human soluble
      thrombomodulin (rhsTM) in plasma and in a monkey model. rhsTM dose-dependently
      prolonged activated partial thromboplastin time (APTT) in the following order:
      humans > monkeys > rats >> rabbits. The prolongation of APTT by rhsTM was also
      observed in protein C-deficient plasma. rhsTM activated protein C and inactivated
      factor Va in human and monkey plasma, but not in rat plasma. These findings
      suggest that the antithrombotic activities of rhsTM are fully expressed in human
      and monkey. Therefore, to evaluate the whole activity of rhsTM in a clinical
      model, tissue factor (TF) was intravenously infused into crab-eating monkeys to
      induce disseminated intravascular coagulation (DIC). Pretreatment with rhsTM
      reduced fall in fibrinogen with a biphasic and moderate dose-dependency curve,
      and reduced thrombin-antithrombin III (TAT) levels with a flat linear dose
      dependency, while heparin prevented fall in fibrinogen with a steep linear dose
      dependency curve without reducing TAT levels. Further evidence suggesting that
      rhsTM activates protein C in vivo was also obtained. Taken together, the data
      indicate that rhsTM fully expresses its antithrombotic activities in human and
      monkey but not in rat and rabbit, and rhsTM prevents TF-induced DIC in monkeys by
      suppressing thrombin generation.

PMID- 9282792
TI  - HPA-1 genotype in arterial thrombosis--role of HPA-1b polymorphism in platelet
      function.
AB  - Recently, the HPA-1b (PlA2) polymorphism of the platelet glycoprotein IIIa has
      been suggested as a genetic risk factor for coronary artery disease. We conducted
      two case-control studies of 103 patients with ischaemic cerebrovascular disease
      (CVD) and 101 patients with ischaemic heart disease (IHD). The groups were
      matched for age, race and sex. No significant differences regarding selected risk
      factors (hypertension, diabetes mellitus, hypercholesterolaemia and smoking) were
      found between case patients and controls. Moreover, we investigated 286 normal
      individuals from the Mediterranean area. Genotyping of HPA-1 was performed by PCR
      allelic specific restriction and single-strand conformation polymorphism
      analysis. The prevalence of HPA-1b was similar among case patients and controls
      (29.2% vs. 25.3% and 26.7% vs. 34.6% for CVD and IHD case-control studies,
      respectively). The HPA-1b allele was found in 36.4% of the normal population.
      Finally, the analysis of platelet function in nine controls with the three
      possible HPA-1 genotypes (three a/a, three a/b and three b/b) indicates that HPA
      1b genotype does not modify either the in vitro platelet aggregation and
      activation profile, nor the GP IIb/IIIa interaction with fibrinogen or von
      Willebrand factor. Our results do not support the role of HPA-1b polymorphism as
      an inherited risk factor for arterial thrombotic disease.

PMID- 9282793
TI  - Reduction of plasma clot stability by a novel factor XIIIa inhibitor from the
      Giant Amazon Leech, Haementeria ghilianii.
AB  - The blood-sucking leech, Haementeria ghilianii, has evolved a number of agents
      that attenuate haemostasis. Recently we have isolated a potent inhibitor of
      factor XIIIa, tridegin, in the salivary glands which is almost certainly involved
      in feeding. Addition of purified natural tridegin to plasma, prior to clotting
      with thrombin, results in clots that deform more readily as adjudged by the
      greatly reduced development of the storage modulus on application of a shear
      force. The increase in the storage modulus in developing plasma clots is a slow
      process and continues for many hours. The effect of tridegin is particularly
      great when the clots are permitted to age in this way, demonstrating the role of
      factor XIIIa in the process. The IC50 for this inhibition is 138 ng/ml. Clots
      formed in the presence of tridegin are also lysed more rapidly in vitro by the
      leech's own fibrinolytic enzyme, hementin (time for 50% lysis, 16.0 +/- 0.8 h
      versus 22.3 +/- 2.0 h, P < 0.05). The synergy with which these agents act
      together may provide lessons for therapy of thrombosis in man.

PMID- 9282794
TI  - Comparison of new rapid methods for D-dimer measurement to exclude deep vein
      thrombosis in symptomatic outpatients.
AB  - Eighty-seven outpatients consecutively admitted to the emergency unit of our
      hospital with clinically suspected first deep vein thrombosis (DVT) of a leg had
      D-dimer levels measured by the following recently introduced fast methods: VIDAS
      (bioMerieux), LPIA (Mitsubishi), Nephelotex (Biopool), Nycocard (Nycomed) and
      Instant.I.A. (Diagnostica Stago). A latex agglutination test (Minutex, Biopool)
      was also performed and a classical ELISA (Gold EIA, Agen) used as reference.
      Venography was performed in all patients, with DVT diagnosed in 42 (37 proximal).
      All the new methods can be adopted in emergency situations, since they are suited
      for individual tests, are rapid and the reagents ready to use. All the methods
      proved to have a good interassay reproducibility. The new D-dimer and latex
      agglutination tests showed negative (88-96%) and positive (63-81%) predictive
      values similar to those of ELISA (92% and 71%, respectively), though the still
      wide confidence intervals suggest larger patient population series be
      investigated. As regards clinical application, the use of these tests to rule out
      DVT should be tested in prospective clinical follow-up trials where
      anticoagulation is withheld in subjects with negative non-invasive reliable
      vascular tests and normal D-dimer levels.

PMID- 9282795
TI  - Increased soluble fibrin monomer and soluble thrombomodulin levels in non-insulin
      dependent diabetes mellitus.
AB  - We measured the plasma levels of fibrinogen, D-dimer, thrombin-antithrombin
      complex (TAT), plasmin-plasmin inhibitor complex (PPIC), soluble fibrin monomer
      (SFM), tissue-type plasminogen activator (t-PA) and thrombomodulin (TM) in
      patients with non-insulin-dependent diabetes mellitus (NIDDM). There were no
      significant differences in the hemostatic parameters between the 77 patients with
      NIDDM and healthy control subjects, although the plasma levels of fibrinogen, D
      dimer, TAT, and PPIC in the NIDDM patients were slightly higher than those in the
      healthy controls. Among the NIDDM patients divided into three groups by the
      urinary albumin excretion (UAE) level, there was no significant difference in age
      or sex among the normo-, micro-, and macroalbuminuria groups, and the HbA1C level
      in the micro- and macroalbuminuria groups were slightly higher than those in the
      normoalbuminuria group. There was no significant difference in activated partial
      thromboplastin time, prothrombin time, fibrinogen, TAT, PPIC, D-dimer, or t-PA
      among these three groups. The plasma SFM and TM levels in the macroalbuminuria
      group were significantly higher than those in the normo- and microalbuminuria
      groups. The relationships between HbA1C and the hemostatic parameters were poor,
      but the plasma TM and SFM levels were significantly correlated with the urine
      albumin index.

PMID- 9282796
TI  - Factor VII C329R: a variant with a disrupted disulfide bond in the catalytic
      domain.
AB  - We report a novel mutation within the coagulation factor VII gene associated with
      a dysfunctional procoagulant factor VII (12% of normal plasma factor VII
      activity; 50% of normal plasma factor VII antigen level). Using heteroduplex
      analysis and subsequent sequencing, we identified a thymine-10,902 to cytosine
      mutation within exon eight of the factor VII gene, encoding for a substitution of
      arginine for cysteine-329 (factor VII C329R) within the heavy chain of factor
      VII. This substitution disrupts a disulfide bond within the factor VII catalytic
      domain and might cause altered conformation of the active site triad.

PMID- 9282797
TI  - De novo mutation of the platelet glycoprotein Ib alpha gene in a patient with
      pseudo-von Willebrand disease.
AB  - Pseudo (or platelet-type)- von Willebrand disease (vWD) is a very rare autosomal
      dominant bleeding disorder caused by an abnormal hyper-responsiveness of the
      platelet membrane glycoprotein (GP) Ib/IX complex, the receptor for von
      Willebrand factor. We found a heterozygous missense mutation in the GPIb alpha
      gene in a sporadic case with pseudo-vWD: Met (ATG) to Val (GTG) at residue 239.
      The mutation was not detected in either parent. Investigation of three variable
      number of tandem repeat loci, D1S80 (MCT118), vWA and D17S5 (YNZ22), confirmed
      paternity and the de novo origin of the mutation. Furthermore, we have shown by
      the TaqI polymorphism analysis, which is located downstream of the GPIb alpha
      gene, that the mutation occurred in the maternal allele. This is the first
      description of de novo mutation occurred in pseudo-vWD and/or platelet GPIb alpha
      gene.

PMID- 9282798
TI  - A patient homozygous for a mutation in the prothrombin gene 3'-untranslated
      region associated with massive thrombosis.
AB  - We describe the first reported case of a thrombophilia patient genetically
      homozygous for a recently described polymorphism in the 3'-UTR (untranslated
      region) of the prothrombin gene. It has previously been demonstrated that this
      genetic variant due to a G to A transition at nucleotide 20210 is common and
      associated with an almost threefold increased risk of venous thrombosis. This
      polymorphism was also shown to be associated with elevated plasma prothrombin
      (factor II) levels, which in itself was found to be a risk factor for venous
      thrombosis. The patient was a healthy young Mexican male who presented with a
      myocardial infarction and subsequent ileofemoral venous thrombosis and massive
      saddle pulmonary embolus. Testing done during his initial hospitalization
      suggested a congenital protein C deficiency. The patient was found to be
      homozygous for the prothrombin gene polymorphism as well as a carrier for factor
      V Leiden. This case strongly implies a clinically significant role for the factor
      II gene mutation in both arterial and venous thrombosis and demonstrates the need
      to perform diagnostic clotting based assays after resolution of acute thrombotic
      events. These findings further support the 'double hit' theory for thrombophilia
      in young patients.

PMID- 9282799
TI  - Diagnosis of acute lower limb deep venous thrombosis with ultrasound: trends and
      controversies.
AB  - Acute deep venous thrombosis of the lower limb is a common and threatening
      condition whose clinical diagnosis is known to be unreliable. Sonography has
      gradually superseded venography as the primary diagnostic procedure. A review of
      the medical literature shows that sonography offers a high level of sensitivity
      and specificity in symptomatic patients but suffers from a lack of sensitivity at
      the calf level and in asymptomatic patients. Technologic progress, as well as
      increased operator experience, may improve sensitivity. Nevertheless, several
      critical issues remain unresolved, such as the significance of free-floating
      thrombi, the usefulness of calf and bilateral examination, the criteria that are
      essential to the diagnosis, the risk of compression sonography, and sonography's
      role in the direct detection of venous emboli.

PMID- 9282800
TI  - Change in hepatic arterial hemodynamics induced by hepatocellular carcinoma
      detected with Doppler sonography.
AB  - PURPOSE: To understand the hemodynamic differences between the hepatic arterial
      branches that supply hepatocellular carcinomas (HCCs) and those that do not, we
      compared the velocity waveforms of both types of arteries. METHODS: Using duplex
      color Doppler sonography, we examined 38 patients with HCC localized within a
      single lobe of the liver and 34 patients with chronic liver disease but without
      HCC (controls). We measured angle-corrected peak systolic velocity and the
      pulsatility index (PI) of color-coded hepatic arteries along the right anterior
      segmental portal branch and the vertical segment of the left portal vein.
      RESULTS: There was no significant difference in peak systolic velocity and PI
      between the arterial branches tested in the controls. In contrast, we found a
      significantly lower PI and a higher peak systolic velocity in the arterial
      branches supplying the tumor than in those not supplying the tumor in patients
      with an HCC 3 cm or larger in diameter (p < 0.05). The degree of these
      hemodynamic changes correlated with the tumor size and the presence or absence of
      tumor thrombus in the major portal branches. CONCLUSIONS: These results indicate
      that the hepatic arterial branch supplying an HCC has a lower impedance than the
      branch not supplying the tumor.

PMID- 9282801
TI  - Intraobserver variability of pulsatility index measurements in three fetal
      vessels in the first trimester.
AB  - PURPOSE: The intraobserver repeatability of pulsatility index measurements in 3
      fetal vessels in the early weeks of gestation was evaluated. METHODS: The
      pulsatility index was calculated from the flow velocity waveforms from 3 fetal
      vessels in a series of 58 uneventful, low-risk, singleton first-trimester
      pregnancies using transvaginal color Doppler sonography. The intraobserver
      repeatability was expressed as the intraclass correlation coefficient. Mean
      menstrual age at the time of the examination was 10.3 weeks (range, 7.6-13).
      RESULTS: Flow velocity waveforms from the umbilical artery, abdominal aorta, and
      middle cerebral artery were obtained in 100% (58/58), 98.3% (57/58), and 100%
      (34/34) of cases, respectively. The intraclass correlation coefficients for these
      vessels were 0.89, 0.79, and 0.93, respectively. CONCLUSIONS: The intraobserver
      repeatability was acceptable for all the vessels studied.

PMID- 9282802
TI  - Congenital masses of the lung: changes in cross-sectional area during gestation.
AB  - PURPOSE: We assessed the growth of congenital masses of the lung during gestation
      using computer-assisted planimetry. METHODS: The prenatal sonograms of 8 fetuses
      with congenital masses of the lung were reviewed. RESULTS: The cross-sectional
      area of the mass and chest were measured on the same transverse image using
      computer-assisted planimetry, and the percentage of the chest occupied by the
      mass was determined for each study. Four masses had pathologic features of type
      II congenital cystic adenomatoid malformation and intralobar sequestration
      (CCAM/ILS), 2 were type II CCAM, 1 was type I CCAM, and 1 was bronchial atresia
      with bronchiectasis. Four masses increased in cross-sectional area during
      gestation, 1 decreased, 2 were essentially unchanged, and 1 showed an initial
      increase in cross-sectional area followed by a decrease later in gestation. No
      consistent growth pattern was seen among masses with similar histologic
      characteristics. The percentage of the cross-sectional area of the chest occupied
      by the mass decreased in 7 fetuses and was virtually unchanged in 1 during
      gestation. All the fetuses survived to term; the infants had an uncomplicated
      postnatal course and underwent surgical resection of the mass during the first
      year of life. CONCLUSIONS: This study showed that in a fetus with a congenital
      mass of the lung and a favorable clinical outcome, growth of the chest exceeds
      any growth of the mass that may occur and masses with the same pathologic
      diagnosis have different patterns of growth in utero.

PMID- 9282803
TI  - Prediction of fetal macrosomia using sonographically measured abdominal
      subcutaneous tissue thickness.
AB  - PURPOSE: We assessed the usefulness of sonographic measurement of abdominal
      subcutaneous tissue thickness in predicting fetal macrosomia (weight > 4,000 g).
      METHODS: Abdominal subcutaneous tissue thickness was measured sonographically in
      133 term fetuses. All studied fetuses were delivered within 72 hours after the
      measurements were taken. RESULTS: One hundred thirteen fetuses were normal size,
      and 20 were macrosomic. The fetal abdominal subcutaneous tissue thickness ranged
      between 3 and 18 mm in all fetuses, with a mean measurement of 8.4 +/- 2.7 mm
      (standard deviation). The mean tissue thickness differed significantly between
      normal and macrosomic fetuses (7.0 mm versus 12.4 mm, respectively; p < 0.0001).
      There was a significant positive correlation between the abdominal subcutaneous
      tissue thickness and the birth weight (r = 0.67, p < 0.0001). The negative
      predictive value for a range of cut-off points between 8 and 13 mm varied between
      84.3% and 100% (for prevalence rates of macrosomia of 5-25%). However, the
      positive predictive value was less than 50% for cut-off values below 11 mm.
      CONCLUSIONS: Sonographic measurement of the subcutaneous tissue thickness of the
      fetal abdomen is useful for ruling out macrosomia.

PMID- 9282805
TI  - Sonographic findings in tuberculous epididymitis and epididymo-orchitis.
AB  - PURPOSE: This paper presents the sonographic findings in scrotums of patients
      affected with tuberculous epididymitis or epididymo-orchitis. METHODS: Eighteen
      patients with a total of 22 abnormal hemiscrotums (4 patients had bilateral
      lesions) underwent scrotal sonography. Pathologic confirmation was obtained via
      epididymectomy in 10 cases, epididymo-orchiectomy in 7 cases, and scrotal
      exploration and biopsy in 3 cases. The histopathologic diagnosis was tuberculous
      epididymitis in 12 cases and epididymo-orchitis in 8 cases. RESULTS: Lesions
      involved the head of the epididymis in 8 cases, the tail in 5 cases, and the
      entire epididymis in 9 cases. The enlarged epididymis was hypoechoic in 13 cases,
      hyperechoic in 2 cases, and of mixed echogenicity in 7 cases. The echotexture was
      heterogeneous in 17 cases and homogeneous in 5 cases. Testicular involvement in 7
      cases appeared as a diffusely enlarged hypoechoic testis in 2 cases, an ill
      defined hypoechoic lesion in 1 case, a well-demarcated hypoechoic lesion in 2
      cases, and multiple small hypoechoic nodules in an enlarged testis in 2 cases.
      Hydrocele, sinus tract, and extratesticular calcifications were seen in 12, 4,
      and 2 cases, respectively. CONCLUSIONS: The heterogeneous and hypoechoic swelling
      of the epididymis or the concomitant hypoechoic lesion of the testis with
      associated sinus tract or extratesticular calcifications may be helpful in the
      diagnosis of tuberculous epididymitis or epididymo-orchitis, especially in
      patients with known genitourinary tuberculosis.

PMID- 9282804
TI  - Cerebrovascular reactivity in hypertensive patients: a transcranial Doppler
      study.
AB  - PURPOSE: We studied the usefulness of transcranial Doppler sonography for
      assessing changes in vasoreactivity in patients with hypertension and the
      hemodynamic consequences of hypertension. METHODS: The study group comprised 25
      patients with chronic severe hypertension and 25 age- and sex-matched healthy
      subjects. Cerebrovascular reserve capacity was assessed by transcranial Doppler
      recording of the blood flow velocity in both middle cerebral arteries before and
      5, 10, 15, and 20 minutes after intravenous injection of 1 g of acetazolamide
      (Diamox). Blood pressure, blood gases, and other blood parameters were also
      measured before and after acetazolamide injection. The sizes of the left atrium,
      left ventricle, and aortic root were measured by echocardiography and correlated
      with the vasoreactivity after acetazolamide injection. RESULTS: After
      acetazolamide injection, no significant changes in blood pressure were observed
      in either group. The mean blood flow velocity in the middle cerebral arteries of
      hypertensive patients (60.8 +/- 2.6 cm/sec) was not significantly different from
      that of controls (58.8 +/- 1.9 cm/sec) before acetazolamide injection. Ten
      minutes after acetazolamide injection, the percentage change in blood flow
      velocity was significantly lower in the hypertensive group (36.2 +/- 4.5%) than
      in the controls (52.6 +/- 3.7%). A significant negative correlation (p < 0.05)
      between decreased vasoreactivity and increased size of the left atrium and aortic
      root was observed. CONCLUSIONS: Vasoreactivity decreases in hypertensive patients
      without neurologic deficits or computed tomography abnormalities. Enlargement of
      the left atrium correlates well with the severity of the impairment in
      vasoreactivity. Transcranial Doppler sonography can be a sensitive tool in the
      investigation of vascular impairment caused by hypertension and in the follow-up
      of hypertensive patients.

PMID- 9282806
TI  - Imaging characteristics of giant myofibroblastoma of the breast diagnosed by
      ultrasound-guided core biopsy.

PMID- 9282807
TI  - Incisional hernia of gallbladder in a patient with gallbladder carcinoma:
      sonographic demonstration.

PMID- 9282808
TI  - Conservatively treated pelvic arteriovenous malformation: noninvasive sonographic
      monitoring during subsequent pregnancy.

PMID- 9282809
TI  - Prenatal sonographic diagnosis of horseshoe kidney.

PMID- 9282810
TI  - Value of sonography in the workup of patients with tuberous sclerosis.

PMID- 9282811
TI  - Use of a green fluorescent protein as a marker for human immunodeficiency virus
      type 1 infection.
AB  - We constructed a recombinant human immunodeficiency virus type 1 (HIV-1) provirus
      called R7-GFP that expresses a modified form of a green fluorescent protein (GFP)
      from the jellyfish Aequorea victoria by substituting GFP-coding sequences for Nef
      coding sequences. Alanine was substituted for serine at amino acid position 65 in
      the modified GFP, resulting in markedly increased fluorescence at an excitation
      wavelength of 488 nm as compared to wild-type GFP. The replication kinetics of R7
      GFP were identical to that measured with an isogenic, nef-negative strain lacking
      GFP. Expression of GFP by replication-competent HIV-1 allowed simultaneous
      quantitation of viral infection and cell surface CD4 levels, revealing rapid and
      nearly complete CD4 downregulation on R7-GFP-infected PBMCs.

PMID- 9282812
TI  - Didanosine but not high doses of hydroxyurea rescue pigtail macaque from a lethal
      dose of SIV(smmpbj14).
AB  - It has been previously reported that hydroxyurea (HU) displays anti-HIV-1
      activity and potentiates the antiviral effects of didanosine (ddI) in vitro. To
      assess the antiviral efficacy of HU in an animal model, the effects of HU and
      ddI, either individually or as combination therapy, were tested in a model using
      infection of pigtail macaque with the acutely fatal variant SIV(smpbj14). At the
      high dosage used (100 mg/kg/day), HU monotherapy failed to protect the exposed
      animals from viral infection and death, which occurred within 10 days
      postinoculation. However, both of the ddI-treated animals (5 mg/kg/day) survived
      the SIV(smmpbj14) lethal dose and displayed a reduction in viral load
      (undetectable SIV RNA or p27gag) in the primary phase of infection. Of the
      animals treated with the combination of drugs, one died at day 18 after infection
      and failed to seroconvert to viral antigens. These data suggest that a high dose
      of HU monotherapy does not protect against death induced by SIV(mmpbj14).
      However, lower doses of HU as monotherapy or combination therapy deserve further
      evaluation for their therapeutic effects.

PMID- 9282813
TI  - Decrease in phosphocreatine level in skeletal muscle of SIV-infected rhesus
      macaques correlates with decrease in intracellular glutathione.
AB  - Loss of skeletal muscle tissue (cachexia) is one of the hallmarks of HIV
      infection. It has been found (1) that creatine kinase, i.e., an enzyme of pivotal
      importance in muscular mitochondrial energy metabolism, is inhibited by oxidative
      glutathiolation, and (2) that reduced glutathione (GSH) is decreased in skeletal
      muscle of SIV-infected rhesus monkeys. We, therefore, have studied the
      phosphocreatine (P-Cr) levels. Muscle tissue from SIV-infected macaques showed
      significantly decreased P-Cr but normal creatine (Cr), ATP, and ADP when compared
      with uninfected macaques. Individual P-Cr levels were significantly correlated
      with GSH. Our findings may explain the dysregulation of energy metabolism in
      cachexia.

PMID- 9282814
TI  - Antiretroviral effect of combined zidovudine and reduced glutathione therapy in
      murine AIDS.
AB  - A combination of antiretroviral drugs acting at different points in the virus
      replication cycle was evaluated in a murine retrovirus-induced immunodeficiency
      model of AIDS (MAIDS). Intramuscular administration of high doses of reduced
      glutathione (GSH, 100 mg/mouse/day) and AZT (0.25 mg/ml in drinking water) was
      found to reduce lymphoadenopathy (92%), splenomegaly (80%), and
      hypergammaglobulinemia (90%) significantly more than AZT alone. Combined
      treatment resulted in a reduction in proviral DNA content of 69, 66, and 60%,
      respectively, in lymph nodes, spleen, and bone marrow. Furthermore, the
      stimulation index of B cells was also significantly higher in animals receiving
      GSH and AZT whereas additional responses were not observed in the T cell
      stimulation index and blood lymphocyte phenotype analyses. In conclusion, the
      administration of high doses of GSH and AZT, a new combination of antiviral
      drugs, seems to provide additional advantages compared to single-agent therapy.

PMID- 9282815
TI  - Structural and functional analysis of negatively charged milk proteins with anti
      HIV activity.
AB  - Several polyanionic reagents such as dextran sulfates, heparin sulfates, and
      negatively charged proteins have been reported to exhibit anti-HIV activity in
      vitro. Particularly potent inhibition has been reported for the milk protein beta
      lactoglobulin (betaLG) on modification by 3-hydroxyphthalic anhydride (3HP). The
      introduction of multiple negatively charged carboxyl groups along the polypeptide
      backbone obviously leads to repulsion within the protein molecule and this is
      likely to affect the specific tertiary, and perhaps also secondary, structure of
      the protein. We used several biophysical techniques to probe the structural
      changes that occur on 3HP modification of betaLG. The results suggest that the
      protein becomes largely unstructured on chemical modification. Although a
      profound anti-HIV activity was measured for 3HP-betaLG, similar antiviral effects
      were observed with two other 3HP-modified milk proteins, alpha-lactalbumin and
      alpha(S2)-casein, but not with the unmodified proteins. Most potent inhibition of
      HIV-1 replication was obtained with 3HP-modified alpha-lactalbumin, which also
      demonstrated the least cytotoxicity. These combined results indicate that HIV
      inhibition is a general property of negatively charged polypeptides and do not
      support a model in which the negatively charged 3HP-betaLG protein interacts in a
      structure-specific manner with the CD4 cell surface receptor for HIV-1 entry.

PMID- 9282816
TI  - Production and characterization of monoclonal antibodies to simian
      immunodeficiency virus envelope glycoproteins.
AB  - Twelve monoclonal antibodies (MAbs), TB1 to TB12, were produced against a soluble
      vaccinia recombinant envelope glycoprotein (gp140) from simian immunodeficiency
      virus SIVmac251. These MAbs recognized SIV gp140 with a relatively high affinity
      (K0.5 from 6.7 x 10(-8) to 4 x 10(-9) M). All the MAbs except TB9, TB11, and TB12
      cross-reacted with HIV-2 envelope glycoproteins, but none of the 12 MAbs
      recognized those from HIV-1. Using a panel of 87 overlapping synthetic peptides
      containing 20 amino acid residues, with an overlap of 10 amino acids and spanning
      the entire primary sequence of gp140, 3 linear epitopes were identified. The
      first mapped with a neutralizing MAb, TB12, which recognized a linear sequence
      around amino acids 28-31 within the N-terminal end of the external envelope
      glycoprotein. The two other new nonneutralizing MAbs recognized linear epitopes
      around amino acid sequence 380-381 by MAbs TB1, TB2, and TB3, and at the
      transmembrane glycoprotein amino acids 581-600 by MAb TB6. Seven of the 12 MAbs,
      TB4, TB5, TB7-9, TB10, and TB11, failed to bind the linear synthetic peptides in
      ELISA. Moreover, among these seven MAbs only MAbs TB4, TB5, TB9, and TB10 failed
      to recognize SIV envelope glycoproteins in Western blot (WB) or ELISA after
      reduction of disulfide bridges by dithiothreitol (DTT), suggesting that they are
      directed against conformational or discontinuous epitopes. It is of interest to
      note that MAb TB10 can block the binding of gp140 to the CD4 receptor when the
      MAb is previously incubated with gp140. Consistent with this result, MAb TB10
      cannot bind to gp140 that has been previously complexed with the CD4 receptor.
      All these results suggest that MAb TB10 recognizes a conformational or
      discontinuous epitope overlapping or close to the CD4-binding site. These
      properties are probably implicated in the neutralizing activity observed with
      this MAb.

PMID- 9282817
TI  - Most potential linear B cell epitopes of Env glycoproteins of feline
      immunodeficiency virus are immunogenically silent in infected cats.
AB  - A battery of sixty-six 20- to 23-amino acid synthetic peptides, partially
      overlapping by 10-12 amino acids, spanning the entire sequence of the envelope
      (Env) glycoproteins of the Petaluma isolate of feline immunodeficiency virus (FIV
      Pet), has been used to map Env linear B cell epitopes. By screening FIV-infected
      cat sera for anti-peptide reactivity, the existence of two immunodominat domains,
      namely the V3 region of the surface (SU) glycoprotein and the domain including
      the highly conserved sequence QNQFF of the transmembrane (TM) glycoprotein, was
      detected; antibody-binding sites were also mapped in the domain overlapping the
      cleavage site between SU and TM encompassing the V6 variable region. Moreover, at
      least two novel linear B epitopes, the former spanning residues 427M-H446 and the
      latter spanning residues 737N-N756 and likely representing a "type-specific"
      determinant, have been revealed. The battery of synthetic peptides was then used
      to immunize outbred Swiss mice in the attempt to reveal other potential sites of
      immunogenicity of the Env glycoproteins. Analysis of peptide-immunized mouse sera
      for anti-peptide reactivity revealed more numerous B cell epitopes, generally
      mapping in different peptides, as compared with those defined in the feline
      system. None of the mouse anti-peptide sera, however, proved neutralizing for FIV
      Pet.

PMID- 9282818
TI  - Cortical cell loss in asymptomatic cats experimentally infected with feline
      immunodeficiency virus.
AB  - Specific pathogen-free cats experimentally infected with feline immunodeficiency
      virus (FIV) were used to evaluate the development of central nervous system
      changes during the asymptomatic stages of viral infection. The brains of
      asyptomatic cats were examined at postinoculation times ranging from 8 weeks to 3
      years for changes in neuron density, glutamate receptor density, and
      synaptophysin immunoreactivity. At 2-3 years postinoculation a small decrease in
      neuronal density was found in layers 2-3 and layer 5 of the frontal cortex (
      14.4%), parietal cortex (-18.1%), and striatum (-29.5%). The only other
      indications of pathology within these regions were a mild diffuse astrogliosis,
      occasional microglial nodules, and the accumulation of satellite cells around
      selected neurons. An average loss of large neurons of 56-68% was seen in the
      cortex of four random source cats euthanized with AIDS. These values contrasted
      with the absence of any significant cell loss in FIV-infected cats 18 weeks after
      inoculation or FIV-negative controls. The loss of neurons in the asymptomatic
      cats showed a significant positive correlation with a decrease in the blood
      CD4:CD8 ratios. Morphometric evaluation of synaptic terminal densities
      immunocytochemically stained with synaptophysin revealed a significant increase
      in the asymptomatic cats at 2-3 years postinoculation that correlated negatively
      with the CD4:CD8 ratios. Random source AIDS cats showed a 34% decrease in
      synaptophysin-immunoreactive profiles. Glutamate binding in the cortex did not
      change significantly in the asymptomatic cats (4-7% decline). Thus,
      experimentally infected specific pathogen-free cats show a loss of cortical
      neurons similar to what has been observed in postmortem studies of humans
      infected with HIV. The detection of neuronal loss during the asymptomatic stage
      of disease and the correlation with the peripheral CD4:CD8 cell ratios indicate
      that neurodegeneration may progress in parallel with peripheral disease.

PMID- 9282819
TI  - High prevalence of false-negative anti-HTLV type I/II enzyme-linked immunosorbent
      assay results in HIV type 1-positive patients.
AB  - A high frequency of false-negative anti-HTLV-I/II ELISA results has been reported
      by several authors. To verify the possible underestimate of the prevalence of
      HTLV-II infection in subjects infected by HIV-1, we used the PCR to investigate
      the presence of HTLV DNA in peripheral blood mononuclear cells (PBMCs) collected
      from a group of 67 HIV-1-positive anti-HTLV-I/II ELISA-negative individuals; the
      study population included 31 patients with HIV-1-related peripheral neuropathy
      (PN), 15 with non-Hodgkin lymphoma (NHL), and 23 without PN or NHL. Two subjects
      had both PN and NHL. All of the patients who were positive at PCR were
      investigated for the presence of serum anti-HTLV-I/II antibodies by means of
      Western blot (WB). Eighteen (26.9%) of the 67 anti-HTLV-I/II ELISA-negative
      patients had HTLV DNA in their PBMCs and WB-detectable serum antibodies directed
      against one or more HTLV antigens. The individuals affected by predominantly
      sensory polyneuropathy (PSP) had a significantly higher prevalence of HTLV DNA
      than the others. All of the patients in whom HTLV-I/HTLV-II discrimination was
      successful had HTLV-II, with the exception of one patient who was infected by
      HTLV-I. The present study confirms the possibility of HTLV infection in the
      absence of ELISA-detectable serum anti-HTLV-I/II antibodies, especially in the
      particular setting of HIV-1-infected individuals. Moreover, the fact that the
      prevalence of HTLV DNA was significantly higher in the subjects affected by
      predominantly sensory polyneuropathy further supports the possibility of an
      association between HIV-1-related PSP and HTLV-II.

PMID- 9282820
TI  - Detection of simian T cell leukemia virus type I infection in seronegative
      macaques.
AB  - Simian species of Asian and African origin are naturally infected with the simian
      T cell leukemia virus type I (STLV-I). Like the closely related human T cell
      leukemia virus type I (HTLV-I), STLV-I is primarily cell associated, and typical
      infections exhibit low viral burdens. Four macaques experimentally inoculated
      with a new STLV-I strain isolated from a sooty mangabey monkey were examined over
      extended periods of time for signs of infection by (1) commercial enzyme
      immunoassay and immunoblot assay for cross-reactive serum antibodies to HTLV-I,
      (2) commercial HTLV-I p24gag antigen-capture assay on supernatants from
      cocultures of macaque peripheral blood mononuclear cells (PBMCs) with human
      PBMCs, and (3) nested PCR amplification of proviral sequences in macaque PBMC
      DNA. The nested PCR assay was 100% specific and detected a single STLV-I copy in
      150,000 PBMCs. In addition, our data show that experimental infection of macaques
      with STLV-I can be serologically silent for more than 43 months.

PMID- 9282821
TI  - Genetic analysis of HIV type 1 group O p24gag sequences from Cameroon and
      Equatorial Guinea.

PMID- 9282822
TI  - Sequence of chemokine receptor gene CCR5 in chimpanzees, a natural HIV type 1
      host.

PMID- 9282823
TI  - Cytokine-induced cytotoxic function expressed by lymphocytes of the innate immune
      system: distinguishing characteristics of NK and LAK based on functional and
      molecular markers.
AB  - Several molecular events are now identifiable during the activation, recognition,
      and killing by natural killer (NK) cells that are distinct from those
      differentiated in response to cytokines during the generation of lymphokine
      activated killer (LAK) cells or during lymphocyte proliferation. Because LAK and
      MHC-unrestricted killing activities also include the prototypic NK targets as
      part of their broad recognition spectra, accurate identification of the complete
      function being studied is critical. In many publications, past and present, only
      NK-sensitive target cells were used (K562, Molt-4, others), and, therefore, the
      results do not necessarily indicate whether the effectors are NK or have
      differentiated into LAK cells. Such a consideration becomes critical when the
      effectors are grown in interleukin-2 (IL-2), and an attempt is made to define
      receptor recognition, signal transduction pathways, and specificity at the
      molecular level. In some instances, effector cells are likely to have stopped,
      therefore merely expressing NK activity, and have also acquired LAK function. The
      identified receptors may not have been unique to NK cells or NK function. Not
      until the targets employed are also confirmed to be NK sensitive, and the
      effectors do not kill NK-resistant targets can the results of molecular studies
      be proposed to represent aspects unique to NK. Reports of the use of IL-2
      expanded NK clones are most likely providing data concerning the biology of LAK
      and not of classic NK. The classic NK activity surveying our blood apparently
      performs an important function, including the ability to respond rapidly to
      certain cytokines and to acquire additional functions and receptors for use in
      destroying a vast array of target cells. It is critical for scientists to
      appreciate the functional distinctions and to identify the molecules and pathways
      unique to each of these curious cytolytic systems.

PMID- 9282824
TI  - Response of patients with dual hepatitis B virus and C virus infection to
      interferon therapy.
AB  - Patients with dual infection with hepatitis B virus (HBV) and delta virus (HDV)
      responded poorly to interferon (IFN) therapy. Little is known about the effect of
      IFN therapy in patients with HBV and hepatitis C virus (HCV) dual infection. The
      patients in two randomized controlled trials with chronic HBV infection were
      retrospectively assayed for HCV markers. The HBV responses to IFN therapy in
      patients with and without HCV markers were compared. An open trial was conducted
      in 4 patients who had lost their serum HBV surface antigen (HBsAg) but had
      continuing HCV viremia and hepatitis. Of the 15 patients seropositive for HCV
      marker(s), only 1 (6.7%) responded with seroclearance of HBV DNA and HBV e
      antigen, as compared with 46 (28%) of 164 HCV-negative patients (p = 0.058).
      Icteric hepatitis developed in 1 patient on emergence of serum HCV RNA in
      association with seroclearance of HBV DNA. In contrast, good response was
      demonstrated in 3 of the 4 patients who had lost serum HBsAg before therapy. The
      results suggest that IFN therapy is not only of limited value in patients with
      dual infection with HBV and HCV but also has a potential risk of severe hepatitis
      if the clearance of one virus removes its suppressive effect on and facilitates
      the emergence of the other. However, patients with continuing HCV hepatitis after
      termination of the chronic HBsAg carrier state responded well to IFN therapy.

PMID- 9282825
TI  - Secondary cytokines interact in sequence with interleukin-1alpha (IL-1alpha) with
      or without macrophage colony-stimulating factor (M-CSF) to further accelerate
      granulopoietic recovery in myelosuppressed animals.
AB  - Interleukin-1alpha (IL-1), by itself, accelerates both granulopoietic and
      thrombopoietic recovery in the 5-fluorouracil (5-FU) myelosuppressed mouse (FUM).
      As a primary cytokine, IL-1 also interacts in concert with macrophage colony
      stimulating factor (M-CSF) to synergistically enhance hematopoietic recovery in
      the FUM. As part of our continuing interest in cytokine sequencing, studies were
      carried out to determine whether the addition of several secondary cytokines (GM
      CSF, IL-3, and IL-6) to IL-1 (+/-M-CSF) would further enhance the stimulatory
      effects of the primary cytokine(s) on hematopoietic recovery in FUM. Throughout
      these studies, IL-1 (+/-M-CSF) was administered for 2 days to the FUM, and the
      secondary cytokines were given either in concert (days 1 and 2) or in sequence
      (days 3-6) or both with the primary cytokine(s). Based on the magnitude of 7-day
      post-5-FU granulocyte recovery, the results demonstrated that the synergistic
      effects of IL-1 + M-CSF treatment on granulopoietic recovery in FUM could not be
      duplicated by substituting either IL-3, IL-6, or GM-CSF for M-CSF. Nonetheless,
      the secondary cytokines were observed to enhance the stimulatory effects of IL-1
      under the following administration schedules: (1) 2 days of IL-1, followed by a
      sequential treatment (days 3-6) with either IL-3 or IL-6, (2) 2 days of IL-1 + GM
      CSF followed by an additional 4 days of GM-CSF alone, and (3) 2 days of IL-1 + GM
      CSF followed by 3-4 days of a combination of GM-CSF and either IL-3 or IL-6.
      Although these cytokine treatment schedules led to an enhanced granulocyte
      recovery (vs. IL-1 alone) in FUM, the day 7 granulocyte numbers never exceeded
      those observed after 2 days of IL-1 + M-CSF. Similarly, granulocyte recovery in
      FUM receiving 2 days of IL-1 + M-CSF followed by either GM-CSF or IL-3 also was
      significantly greater than that observed with IL-1 + M-CSF alone. In contrast,
      however, the sequential administration of IL-6 with IL-1 + M-CSF, unlike IL-1,
      failed to further enhance granulopoietic recovery, suggesting that there may be
      an antagonism between IL-6 and M-CSF in the FUM. In summary, therefore, the
      secondary cytokines were found to interact more effectively when they were
      administered in sequence, rather than in concert, with both IL-1 and IL-1 + M
      CSF.

PMID- 9282826
TI  - HIV-1 p17 and IFN-gamma both induce fructose 1,6-bisphosphatase.
AB  - The p17 matrix protein of the human immunodeficiency virus type 1 (HIV-1) plays a
      crucial role in AIDS pathogenesis. It orchestrates viral assembly and directs the
      preintegration complex to the nucleus of infected cells. Recently, the three
      dimensional structure of p17 was shown to resemble that of interferon-gamma (IFN
      gamma), suggesting that both proteins might share analogous functions. We
      demonstrate that in monocytes, p17 shares with IFN-gamma the ability to induce
      1alpha-hydroxylase activity and to activate fructose 1,6-bisphosphatase gene
      expression in the presence of 25-hydroxyvitamin D3. However, p17 does not bind to
      the IFN-gamma cell membrane receptor and fails to increase expression of IFN
      gamma-induced proteins, such as tryptophanyl-tRNA synthetase, Fc gammaRI, and HLA
      DR or B7/BB1 antigens. Altogether, our results raise the possibility that the
      structural resemblance between p17 and IFN-gamma causes the selective activation
      of a common pathway resulting in the production of 1,25-dihydroxyvitamin D3. We
      also found that unlike IFN-gamma, p17 increases the intracellular ATP content.
      Since transport of the HIV-1 preintegration complex through the nuclear membrane
      is an ATP-dependent process, our observation suggests that p17 plays a double
      role in this active transport, not only by acting as a chaperone molecule but
      also by recruiting the necessary energy for this process.

PMID- 9282827
TI  - Zinc supplementation reconstitutes the production of interferon-alpha by
      leukocytes from elderly persons.
AB  - The elderly are more prone to virus infections and neoplasias than are young
      adults. During a virus infection, interferon-alpha (IFN-alpha), proteins with
      antiviral, antiproliferative, and immunomodulatory properties, are transiently
      expressed. We here report that peripheral white blood cells from 16 subjects with
      a mean age of 72 years yielded less IFN when stimulated with a virus in vitro
      than those from 16 young adults with a mean age of 28 years. Monocytes are the
      main source of this IFN. However, yields of another monocyte product, interleukin
      6 (IL-6), were greater in cells from the older subjects than from the young
      adults, so there is no general defect in monocytes from the former.
      Immunodeficiency in the elderly has been reported to be associated with a
      deficiency of zinc. When cultures of white blood cells from the elderly were
      supplemented with 15 microM zinc (the physiologic concentration), they produced
      IFN in amounts comparable to those from the younger subjects.

PMID- 9282828
TI  - Cloning and expression of bovine interleukin-15: analysis and modulation of
      transcription by exogenous stimulation.
AB  - The bovine interleukin-15 (IL-15) sequence was cloned from abomasal lymph node
      mRNA by enzymatic amplification of cDNA using human primers proximal to and
      including the translation start and stop sites. The open reading frame is 486
      base pairs in length, and the proposed protein sequence shows 78.4% and 73.5%
      similarity with that predicted for the human and mouse sequences, respectively.
      Expressed and purified recombinant bovine IL-15 in the absence of the 48-amino
      acid leader sequence stimulated the proliferation of bovine lymphoblast cells at
      least 12-fold over background at maximum concentration levels. Competitive
      reverse transcriptase-polymerase chain reaction analysis showed constitutive
      levels of IL-15 mRNA within a broad range of tissues and cell types.
      Lipopolysaccharide addition to adherent lymph node populations caused moderate
      increases in IL-15 transcription, whereas the addition of phorbol 12-myristate 13
      acetate and calcium ionophore failed to induce gene expression for this cytokine.
      Transcription of IL-15 was also downregulated in the presence of low
      concentrations of human recombinant interleukin-2.

PMID- 9282829
TI  - Cytokine profiles of stimulated blood lymphocytes in asthmatic and healthy
      adolescents across the school year.
AB  - T cell cytokines play an important role in mediating airway inflammation in
      asthma. The predominance of a Th2 cytokine profile, particularly interleukin (IL)
      4 and IL-5, is associated with the pathogenesis and course of asthma. The aim of
      this study was to test the hypothesis that a stressful life event alters the
      pattern of cytokine release in asthmatic individuals. Thirteen healthy controls
      and 21 asthmatic adolescents gave blood samples three times over a semester:
      midsemester, during the week of final examinations, and 2-3 weeks after
      examinations. Interferon-gamma (IFN-gamma), IL-2, IL-4, and IL-5 were measured
      from supernatants of cells stimulated with PHA/PMA for 24 h. Cells from asthmatic
      subjects released significantly more IL-5 during the examination and
      postexamination periods, whereas cells from healthy controls released
      significantly more IL-2 during the midsemester and examination periods, thereby
      indicating a bias for a Th2-like pattern in asthmatics and a Th1-like pattern in
      healthy controls. IL-4 and IL-5 production showed a marked decrease during and
      after examinations in healthy controls, whereas this decline was absent in
      asthmatics. The ratios of IFN-gamma:IL-4 and IFN-gamma:IL-5 also revealed
      significant changes in the profile of cytokine release across the semester. These
      results indicate differential cytokine responses in asthmatics that may become
      pronounced during periods of cellular activation.

PMID- 9282831
TI  - Human flavin-containing monooxygenase form 3: cDNA expression of the enzymes
      containing amino acid substitutions observed in individuals with
      trimethylaminuria.
AB  - Trimethylaminuria is an autosomal recessive human disorder affecting a small part
      of the population as an inherited polymorphism. Individuals diagnosed with
      trimethylaminuria excrete relatively large amounts of trimethylamine in their
      urine, sweat, and breath, and this results in a fishy odor characteristic of
      trimethylamine. Activity of the human flavin-containing monooxygenase (FMO) has
      been proposed to be deficient in trimethylaminuria patients causing a decrease in
      the metabolism of trimethylamine that results in a fishy body odor. Cohorts of
      Australian, American, and British individuals suffering from trimethylaminuria
      have been identified. The human FMO3 cDNA was amplified from lymphocytes of
      affected patients. We report preliminary evidence of substitutions detected by
      screening of the cDNA and genomic DNA. The variant human FMO3 cDNA was
      constructed from wild type human FMO3 cDNA by site-directed mutagenesis as
      maltose-binding protein fusions. Five distinct human FMO3 mutants were expressed
      as fusion proteins in Escherichia coli and compared with wild type human FMO3
      maltose-binding proteins (FMO3-MBP) for the N-oxygenation of 10-[(N,N
      dimethylamino)pentyl]-2-(trifluoromethyl)phenothiazine, tyramine, and
      trimethylamine. Human Lys158 FMO3-MBP and, to a greater extent, human Glu158 FMO3
      MBP efficiently N-oxygenated the three amine substrates. Human Lys158 Ile66 FMO3
      MBP, Glu158 Ile66 FMO3-MBP, Lys158 Leu153 FMO3-MBP, and Glu158 Leu153 FMO3-MBP
      were all constructed as mutants identified as possible FMO3 variants responsible
      for trimethylaminuria and were found to be inactive as N-oxygenases. The results
      suggest that mutations at codons 66 and 153 of FMO3 can cause trimethylaminuria
      in humans. We observed a common polymorphism of Lys to Glu at codon 158 of FMO3
      that segregated with almost equal allele frequencies in a number of control
      Australian and North American samples studied. The Lys158 to Glu158 human FMO3
      polymorphism does not decrease trimethylamine N-oxygenation for the cDNA
      expressed enzyme and thus does not appear to be causative of trimethyaminuria.
      The data show that the functional activity of human FMO3 can be significantly
      altered by amino acid changes that have been observed in individuals with
      clinically diagnosed trimethylaminuria.

PMID- 9282830
TI  - Microbial superantigens stimulate T cells by the superantigen bridge and
      independently by a cytokine pathway.
AB  - Superantigens cross-link the MHC II molecule on accessory cells with the Vbeta
      region of the T cell receptor (TCR). In this study, we compared the capacity of
      established superantigens for inducing cytokine release. The experimental
      protocol was generated to answer the question whether all superantigen effects
      are transmitted by the MHC/TCR cross-linkage and induce mainly a T cell response.
      We found that TSST-1, ExFTA, and SEC3 differed from all other superantigens
      tested because they stimulated a stronger monokine release. T cell proliferation
      after challenge with these superantigens was mainly mediated by a cytokine
      pathway and not by the cross-linkage of MHC and TCR. For the other superantigens,
      we were able to demonstrate that major immunomodulatory effect is mediated by the
      superantigen bridge. With the exception of these three superantigens, the
      proliferative response of superantigens correlated with their Vbeta specificity.
      Interleukin-1 (IL-1) and IL-6 were induced in monocytes by all superantigens,
      whereas tumor necrosis factor-alpha (TNF-alpha) was induced in T cells and by
      some superantigens, also in monocytes. IL-2 was always induced by the
      superantigen bridge, whereas interferon-gamma (IFN-gamma) was also induced
      indirectly by monokines. Collectively, our results indicate that not all
      superantigens are suitable for investigating superantigen-specific effects, as
      they show indirect (mitogenic) side effects. Observations for an individual
      superantigen are, therefore, not transferable to all other superantigens.

PMID- 9282832
TI  - Detoxication of tyramine by the flavin-containing monooxygenase: stereoselective
      formation of the trans oxime.
AB  - In the presence of pig or adult human liver microsomes, tyramine was metabolized
      to the corresponding trans oxime through the intermediacy of the hydroxylamine.
      The requisite intermediate, (4-hydroxyphenethyl)hydroxylamine, was retroreduced
      to tyramine or converted stereoselectively to the trans oxime in the presence of
      pig or adult human liver microsomes. Studies of the effect of metabolic
      inhibitors suggested that formation of the trans oxime and retroreduction of the
      hydroxylamine were largely dependent on NADPH and the flavin-containing
      monooxygenase (FMO) and cytochrome P450, respectively. The conclusion that FMO
      was predominantly responsible for trans oxime formation in human liver microsomes
      was based on the effect of incubation conditions on tyramine N-oxygenation and
      the observation that cDNA-expressed human FMO3 also N-oxygenated tyramine to give
      exclusively the trans oxime. The synthetic hydroxylamine and oxime metabolites of
      tyramine were examined for affinity to human and animal dopamine and serotonin
      receptors and the human dopamine transporter. For all of the receptors and for
      the transporter examined, the avidity of the hydroxylamine and oximes was greater
      than 10 microM and beyond the effective concentration for physiological
      relevance. The results suggested that tyramine was sequentially N-oxygenated in
      the presence of pig and human liver microsomes and cDNA-expressed FMO3 to the
      hydroxylamine and then to the di-N-hydroxylamine that was spontaneously
      dehydrated to the trans oxime. This may be facilitated by FMO through a
      nondissociative substrate-enzyme interaction. Based on the biogenic amine
      receptor or transporter affinity for the hydroxylamine and oxime metabolites of
      tyramine, N-oxygenation of tyramine by pig or human liver FMO may represent a
      detoxication reaction that terminates the pharmacological activity of tyramine.

PMID- 9282833
TI  - Anomalous structure-activity relationships of 13-homo-13-oxarotenoids and 13-homo
      13-oxadehyrorotenoids.
AB  - Cube resin, used as an insecticide/miticide and piscicide, contains in decreasing
      amounts rotenone (1), deguelin (2), the 6a,12a-dehydro derivatives of rotenone
      (3) and deguelin (4), and the newly-discovered 13-homo-13-oxa-6a,12a-dehydro
      analogs [referred to as oxadehydrorotenone (5) and -deguelin (6)]. These six
      rotenoids were compared for potency as inhibitors of NADH:ubiquinone
      oxidoreductase activity and for organismal toxicity to mosquito larvae, goldfish,
      and mice and cytotoxicity in three mammalian cell lines (Hepa 1C1C7, MCF 7, and
      NB 41A3). Although rotenoids 3-6 contribute very little to the overall activity
      of cube resin, there were two surprising aspects to the structure-activity
      relationships. First, 1 was 7-15-fold more active than 2 in the cytotoxicity
      assays of 4-day duration but not in the other systems. This difference in
      cytotoxicity is not due to specificity at the oxidoreductase target but instead
      to more extensive cytochrome P450-dependent (piperonyl butoxide-sensitive)
      detoxification of 2 than of 1. Second, the observed potency increase on
      conversion of dehydrorotenone to either rotenone or oxadehydrorotenone suggests
      that combining both structural changes to form cis-13-homo-13-oxarotenone (8)
      might result in maximal activity. Accordingly, 5 was reduced with
      diisobutylaluminum hydride to the trans-isomer 7 and then epimerized with aqueous
      pyridine to the cis-isomer 8 of the same configuration as 1. Surprisingly, 8 was
      much less active than 1. This is rationalized on the basis of conformational
      changes in the B/C ring system and decreasing dihedral angle (determined by X-ray
      crystallography and/or molecular modeling) between the A and D rings that follow
      the potency order, i.e., rotenoids 1 and 2 > oxadehydrorotenoids 5 and 6 > trans-
      and cis-oxarotenoids 7 and 8 > dehydrorotenoids 3 and 4. Thus, the novel
      oxarotenoids and oxadehydrorotenoids help define the conformation optimal for
      NADH:ubiquinone oxidoreductase inhibition and toxicity.

PMID- 9282834
TI  - Identification of quinol thioethers in bone marrow of hydroquinone/phenol-treated
      rats and mice and their potential role in benzene-mediated hematotoxicity.
AB  - Metabolism of benzene is required to produce the classical hematological
      disorders associated with its exposure. After coadministration of hydroquinone
      (0.9 mmol/kg, ip) and phenol (1.1 mmol/kg, ip) to male Sprague-Dawley rats and
      DBA/2 mice, 2-(glutathion-S-yl)hydroquinone was identified in the bone marrow of
      both species. 2,5-Bis(glutathion-S-yl)hydroquinone, 2,6-bis(glutathion-S
      yl)hydroquinone, and 2,3,5-tris(glutathion-S-yl)hydroquinone were also observed
      in the bone marrow of rats but were detected only sporadically in mice. Both
      species produced 2-(cystein-S-ylglycinyl)hydroquinone, 2-(cystein-S
      yl)hydroquinone, and 2-(N-acetylcystein-S-yl)hydroquinone, indicating the
      presence of a functional mercapturic acid pathway in bone marrow. The ability of
      bone marrow to acetylate 2-(cystein-S-yl)hydroquinone and deacetylate 2-(N
      acetylcystein-S-yl)hydroquinone was confirmed in vitro. Total quinol thioether
      concentrations were higher in, and eliminated more slowly from, the bone marrow
      of mice. Intravenous injection of 100 micromol/kg 2-(glutathion-S-yl)hydroquinone
      to rats gave rise to substantially lower bone marrow C(max) and AUC values
      compared to values found following coadministration of hydroquinone/phenol,
      suggesting that the major fraction of the GSH conjugates present in bone marrow
      are formed in situ. Finally, the erythrotoxicity of several of these conjugates
      was determined in rats using the erythrocyte 59Fe incorporation assay.
      Administration of 2,3,5-tris(glutathion-S-yl)hydroquinone (17 micromol/kg, iv),
      2,6-bis(glutathion-S-yl)hydroquinone (50 micromol/kg, iv), and benzene (11
      mmol/kg, sc) significantly decreased 59Fe incorporation into reticulocytes to 45
      +/- 6%, 28 +/- 3%, and 20 +/- 9% of control values, respectively. Although the
      doses of 2,3,5-tris(glutathion-S-yl)hydroquinone and 2,6-bis(glutathion-S
      yl)hydroquinone represented only 0.2% and 0.4% of the dose of benzene, both
      conjugates reduced 59Fe incorporation to the same degree as benzene. 2
      (Glutathion-S-yl)hydroquinone had no effect at the dose tested (200 micromol/kg,
      iv). In summary, these data suggest that hydroquinone-glutathione conjugates are
      erythrotoxic and may contribute to benzene-mediated hematotoxicity.

PMID- 9282835
TI  - Characterization of amino acid and glutathione adducts of cis-2-butene-1,4-dial,
      a reactive metabolite of furan.
AB  - Metabolic activation of the hepatocarcinogen furan yields metabolites that react
      covalently with proteins. cis-2-Butene-1,4-dial is a microsomal metabolite of
      furan. This reactive aldehyde is thought to be the toxic metabolite that is
      responsible for the carcinogenic activity of furan. In order to characterize the
      chemistry by which this unsaturated dialdehyde could alkylate proteins, the
      products formed upon reaction of cis-2-butene-1,4-dial with model nucleophiles in
      pH 7.4 buffer were investigated. N(alpha)-Acetyl-L-lysine (AcLys) reacts with cis
      2-butene-1,4-dial to form N-substituted pyrrolin-2-one adducts. N-Acetyl-L
      cysteine (AcCys) reacts rapidly with cis-2-butene-1,4-dial to form multiple
      uncharacterized products. The inclusion of AcLys in this reaction mixture yielded
      an N-substituted 3-(S-acetylcysteinyl)pyrrole adduct which links the two amino
      acid residues. Related compounds were isolated when cis-2-butene-1,4-dial and
      glutathione (GSH) were combined. In this case, cis-2-butene-1,4-dial cross-linked
      two molecules of GSH resulting in either cyclic or acyclic adducts depending on
      the relative GSH concentration. Incubation of furan with rat liver microsomes in
      the presence of [glycine-2-3H]GSH led to the formation of radioactive peaks that
      coeluted with synthetic standards for the bisgluthathione conjugates. These
      studies demonstrate that the reactive cis-2-butene-1,4-dial formed during the
      microsomal oxidation of furan reacts rapidly and completely with amino acid
      residues to form pyrrole and pyrrolin-2-one derivatives. Therefore, this
      metabolite is a likely candidate for the activated furan derivative that binds to
      proteins. The ease with which cis-2-butene-1,4-dial cross-links amino acids
      suggests that pyrrole-thiol cross-links may be involved in the toxicity observed
      following furan exposure.

PMID- 9282836
TI  - Efficient scavenging of fatty acid oxidation products by aminoguanidine.
AB  - Lipid oxidation leads to the formation of reactive aldehydes that may play an
      important role in atherogenesis by altering the normal pathway of lipoprotein
      metabolism and by exerting toxic effects on vascular wall components. Recent
      studies indicate that advanced glycation end products, which form spontaneously
      from the reaction of reducing sugars with amino groups, may promote oxidative
      damage in vivo. Moreover, the pharmacological inhibitor of advanced glycation
      aminoguanidine has been shown to lower circulating low-density lipoprotein levels
      in human subjects and to inhibit certain oxidative reactions in vitro. To define
      more precisely the potential interaction of AG with oxidized lipids, we have
      studied and identified the major products that form from the reaction of AG with
      the oxidation products 4-hydroxynonenal and malondialdehyde. AG was found to be
      an efficient scavenger of alpha,beta-unsaturated aldehydes when compared to
      nucleophilic amino acids (Cys, Lys, His), suggesting that one of its mechanisms
      of action in vivo is to protect tissue constituents from the damaging effects of
      oxidative stress.

PMID- 9282837
TI  - Identification of subdomain IB in human serum albumin as a major binding site for
      polycyclic aromatic hydrocarbon epoxides.
AB  - Covalent adducts between serum albumin and low molecular weight organic
      electrophiles are formed with a high degree of regioselectivity mostly for
      nucleophilic amino acid residues located in subdomains IIA and IIIA. Previous
      studies have indicated that diol epoxide metabolites of polycyclic aromatic
      hydrocarbons (PAH) may target residues in a different subdomain. The
      regioselectivity of PAH epoxide and diol epoxide binding was examined in this
      study by reaction of human serum albumin in vitro with the racemic trans,anti
      isomers of 7,8-dihydrobenzo[a]pyrene-7,8-diol 9,10-epoxide (1), 2,3
      dihydrofluoranthene-2,3-diol 1,10b-epoxide (2), 1,2-dihydrochrysene-1,2-diol 3,4
      epoxide (5), 6-methyl-1,2-dihydrochrysene-1,2-diol 3,4-epoxide (6), 5-methyl-1,2
      dihydrochrysene-1,2-diol 3,4-epoxide (7), 3,4-dihydrobenzo[c]phenanthrene-3,4
      diol 1,2-epoxide (8), 11,12-dihydrobenzo[g]chrysene-11,12-diol 13,14-epoxide (9),
      and 11,12-dihydrodibenzo[a,l]pyrene-11,12-diol 13,14-epoxide (10) and the racemic
      epoxides cyclopenta[cd]pyrene 3,4-epoxide (3) and benzo[a]pyrene 4,5-epoxide (4)
      followed by determination of the linkage site. Adducted albumin was digested
      enzymatically, and digests were chromatographed by reversed-phase HPLC to purify
      peptide adducts, which were analyzed by electrospray ionization collision-induced
      dissociation (CID) tandem mass spectrometry. Product ion spectra revealed that
      adducts fragmented predominantly by cleavage of the peptide-PAH bond with
      retention of charge by the peptide as well as by the hydrocarbon. Peptide
      sequences were determined by MS/MS analysis of the peptide ions formed by in
      source CID to cleave the adduct bond. Longer peptide sequences established site
      selectivity by virtue of their uniqueness, while shorter sequences revealed the
      reactant amino acid within the site. Epoxide 4 and diol epoxides 1, 2, 5, and 6
      reacted predominantly with His146; epoxide 3 and diol epoxides 7-9 reacted
      predominantly with Lys137. Both residues are situated in subdomain IB. The
      binding site for 10 could not be determined uniquely, but one of the several
      possibilities was Lys159, which is also located in subdomain IB. The results,
      taken together with previous findings, demonstrate that the reaction of
      polycyclic aromatic hydrocarbon epoxides with human serum albumin is highly
      selective for a small number of residues in subdomain IB.

PMID- 9282838
TI  - Oxo substituents markedly alter the phase II metabolism of alpha
      hydroxybutenylbenzenes: models probing the bioactivation mechanisms of tamoxifen.
AB  - The P450-catalyzed hydroxylation of tamoxifen to give alpha-hydroxytamoxifen [(E)
      4-{4-[2-(dimethylamino)ethoxy]phenyl}-3,4-diphenyl-3-buten-2- ol] and subsequent
      formation of reactive sulfate esters which alkylate DNA has been proposed to be a
      potential carcinogenic pathway for tamoxifen. In the present study, the ability
      of alpha-hydroxytamoxifen analogs to form GSH and sulfate conjugates was
      investigated in order to understand the structural features influencing
      reactivity. The para oxo analogs 1 [1-(4-methoxyphenyl)-3-hydroxy-1-butene], 2 [1
      (4-hydroxyphenyl)-3-hydroxy-1-butene], and 4 [1-(4-hydroxyphenyl)-1-phenyl-3
      hydroxy-1-butene] reacted with GSH instantaneously under strong acidic conditions
      to yield GSH conjugates in greater than 90% yields. Interestingly, the meta
      phenolic analogs 3 [1-(3-hydroxyphenyl)-3-hydroxy-1-butene] and 5 [1-(3
      hydroxyphenyl)-1-phenyl-3-hydroxy-1-butene] did not react with GSH to any
      significant extent under similar conditions. Characterization of the GSH
      conjugates with 1H-NMR, electrospray mass spectrometry, and UV showed that all of
      the conjugates resulted from attack of GSH at the alpha-position of the
      substrates with displacement of the hydroxyl group. The formation of a single
      pair of diastereomeric conjugates strongly supported adduct formation to proceed
      through a direct S(N)2 displacement mechanism and not through a quinone methide
      (4-alkyl-2,5-cyclohexadien-1-one) intermediate. At physiological pH and
      temperature only the para hydroxy analogs 2 and 4 gave GSH conjugates, a reaction
      which seems to be catalyzed by isoforms of glutathione S-transferase. Similar
      substituent effects were observed in the sulfotransferase-mediated formation of
      alpha-hydroxy sulfate esters in that only the para hydroxy analogs formed
      conjugates at the aliphatic hydroxyl group. Finally, the present investigation
      showed a remarkable difference in the reactivities of para and meta phenolic
      analogs of alpha-hydroxybutenylbenzenes toward GSH and sulfate conjugation
      reactions.

PMID- 9282839
TI  - Prooxidant-initiated lipid peroxidation in isolated rat hepatocytes: detection of
      4-hydroxynonenal- and malondialdehyde-protein adducts.
AB  - Toxicity associated with prooxidant-mediated hepatic lipid peroxidation is
      postulated to originate from the interaction of the aldehydic end products of
      lipid peroxidation with cellular constituents. The principal alpha,beta
      unsaturated aldehydic products of lipid peroxidation, 4-hydroxy-2-nonenal (4-HNE)
      and malondialdehyde (MDA), are known to modify proteins through covalent
      alkylation of lysine, histidine, and cysteine amino acid residues. To detect and
      characterize the formation of 4-HNE- and MDA-adducted proteins during prooxidant
      initiated lipid peroxidation, rabbit polyclonal antibodies were raised to 4-HNE
      sulfhydryl, dinitrophenylhydrazine (DNPH)-4-HNE-sulfhydryl, and MDA-amine
      conjugates of keyhole limpet hemocyanin (KLH). Each antiserum displayed high
      antibody titers to either 4-HNE-metallothionein, DNPH-albumin, or MDA-albumin
      adducts when measured by ELISA. To study the formation of 4-HNE- and MDA-protein
      adducts during prooxidant-initiated cellular injury, isolated hepatocytes were
      exposed to either carbon tetrachloride or iron/ascorbate for 2 h. Indices of
      hepatocellular oxidative stress (i.e., cell viability and glutathione status) and
      lipid peroxidation (i.e., formation of 4-HNE, protein carbonyls, and MDA) were
      monitored continuously. Hepatocellular viability was affected moderately by
      carbon tetrachloride, while cellular reduced glutathione status was moderately
      affected by both iron/ascorbate and carbon tetrachloride. Levels of MDA and
      protein carbonyls increased dramatically with both prooxidants, whereas 4-HNE
      levels did not change significantly over the time course studied. In addition,
      hepatocellular proteins were immunoprecipitated with each antiserum, and aldehyde
      modified immunopositive proteins were detected by immunoblotting. Prooxidant
      induced increases in MDA corresponded with increases in intensity and number of
      MDA-adducted proteins over the time course studied. A total of 13 MDA-modified
      proteins (20, 25, 28, 30, 33, 38, 41, 45, 80, 82, 85, 130, and 150 kDa) were
      detected with the MDA-amine antiserum. Additionally, both iron/ascorbate- and
      carbon tetrachloride-induced formation of DNPH-derivatizable protein carbonyls
      corresponded quantitatively with the ability to detect specific proteins (80,
      100, 130, and 150 kDa) with the DNPH-4-HNE-cysteine antiserum. Neither CCl4 nor
      iron/ascorbate elicited changes in 4-HNE or induced the formation of 4-HNE
      modified proteins when assessed by immunoprecipitation-immunoblot analysis with
      the 4-HNE-sulfhydryl antiserum. In all instances detection of aldehyde-modified
      proteins was not associated with cell death and may be related to the function of
      these proteins as aldehyde-binding proteins which sequester electrophilic
      molecules during oxidative liver injury.

PMID- 9282840
TI  - Binding of nickel(II) and copper(II) to the N-terminal sequence of human
      protamine HP2.
AB  - A potentiometric and spectroscopic (UV/vis and CD) study of Cu(II) and Ni(II)
      binding to the N-terminal pentadecapeptide of human protamine HP2 (HP2(1-15)) was
      performed. The results indicate that the N-terminal tripeptide motif Arg-Thr-His
      is the exclusive binding site for both metal ions at a metal to HP2(1-15) molar
      ratio not higher than 1. The very high value of protonation-corrected stability
      constant (log *K) for Ni(II)-HP2(1-15) complex, -19.29, indicates that HP2 has
      the potential to sequester Ni(II) from other peptide and protein carriers,
      including albumin. The same is likely for Cu(II) (log *K = -13.13). The CD
      spectra of Cu(II) and Ni(II) complexes of HP2(1-15) indicate that the N-terminal
      metal binding affects the overall conformation of the peptide that, in turn, may
      alter interaction of HP2 with DNA. These results imply HP2 as a likely target for
      the toxic metals Ni(II) and Cu(II).

PMID- 9282841
TI  - Mediation of oxidative DNA damage by nickel(II) and copper(II) complexes with the
      N-terminal sequence of human protamine HP2.
AB  - The potential of Ni(II) and Cu(II) complexes with Arg-Thr-His-Gly-Gln-Ser-His-Tyr
      Arg-Arg-Arg-His-Cys-Ser-Arg-amide (HP2(1-15)), a peptide modeling the N-terminal
      amino acid sequence of human protamine HP2, to mediate oxidative DNA damage was
      studied by measurements of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG)
      generation from 2'-deoxyguanosine (dG) and calf thymus DNA and by formation of
      double-strand breaks in calf thymus DNA. The concentrations of reagents were 0.1
      mM dG and the metal-HP2(1-15) complex, 1 mM H2O2, 1.5 mM DNA (per phosphate
      group), 100 mM phosphate buffer, pH 7.4, ambient O2. Samples were incubated at 37
      degrees C for 16-24 h. The Cu(II)-HP2(1-15) complex was found to be an effective
      promoter of the formation of 8-oxo-dG from both dG and DNA with ambient O2
      (approximately 13- and 3-fold increase versus the oxidant alone, respectively)
      and H2O2 (approximately 25-fold increase in either case). The Ni(II)-HP2(1-15)
      complex was ineffective with O2 versus 8-oxo-dG production from both substrates
      but markedly enhanced the attack of H2O2 on dG and DNA (approximately 5-fold
      increase of 8-oxo-dG production in either case). Both Cu(II)- and Ni(II)-HP2(1
      15) equally promoted double-strand scission by H2O2 in calf thymus DNA. The
      promotion by the complexes of dG and DNA oxidation with H2O2 was accompanied by
      oxidative damage to the complexes themselves, consisting of decreasing contents
      of their His (to approximately 50% of control in either complex) and especially
      Tyr (down to 48% of control in Cu(II)- and 19% in Ni(II)-HP2[1-15]) residues, as
      well as appearance of aspartic acid, the known oxidation product of His residues
      in peptides (up to 22% vs Gly for Cu(II)- and 10% for Ni(II)-HP2(1-15)). The
      above results provide a novel chemical mechanism of Cu(II) and Ni(II) toxicity
      and may have wide implications for reproductive and transgenerational effects of
      metal exposure.

PMID- 9282842
TI  - Endovascular occlusion of the carotid or vertebral artery with temporary proximal
      flow arrest and microcoils: clinical results.
AB  - PURPOSE: To determine the clinical effectiveness of parent artery occlusion of
      the carotid or vertebral artery by means of temporary proximal flow arrest and
      microcoils. METHODS: Nineteen parent artery occlusions (15 carotid, four
      vertebral) were performed in 19 patients who successfully passed a balloon test
      occlusion. In these patients, endovascular occlusion of the carotid or vertebral
      artery was accomplished with the use of temporary proximal flow arrest and
      microcoils. RESULTS: All 19 parent arteries were occluded. Eighteen patients
      (95%) had good outcomes and one (5%) had a poor outcome. Fourteen patients (74%)
      had no complications and five (26%) had complications, of whom only one was left
      with a permanent neurologic deficit. Three (60%) of the complications were the
      result of delayed ischemic events after parent artery occlusion and were not
      predicted by balloon test occlusion. CONCLUSION: Endovascular occlusion with
      temporary proximal flow arrest and microcoils can be done effectively and
      successfully. The predictive value of the balloon test occlusion is the major
      complicating factor, as it is with balloon occlusion. This technique offers an
      additional tool that can be used for endovascular occlusion of the carotid or
      vertebral artery and seems to be less difficult technically. It is our primary
      technique for parent artery occlusion.

PMID- 9282843
TI  - Endovascular treatment of ophthalmic segment aneurysms with Guglielmi detachable
      coils.
AB  - PURPOSE: To evaluate the safety and efficacy of endovascular treatment of
      ophthalmic segment aneurysms with Guglielmi detachable coils (GDCs), as well as
      the primary indications for such treatment. METHODS: We conducted a prospective
      study of 26 patients with 28 aneurysms of the ophthalmic segment in whom
      treatment with GDCs was attempted. Anatomic results were measured by statistical
      analysis of variance for such factors as age, sex, presence of subarachnoid
      hemorrhage, anatomic type (ophthalmic or superior hypophyseal), size of
      aneurysmal sac, and width of aneurysmal neck. Clinical evaluation and control
      angiography were performed at 6 and 18 months. RESULTS: Overall, complete
      occlusion was obtained in 14 aneurysms (50%) and small residual necks were left
      in 11 aneurysms (39%). Three treatment attempts failed (11%). Complete occlusion
      was obtained in 76% of small-necked aneurysms as opposed to 9% of aneurysms with
      a large neck. The best predictor of anatomic result was the size of the
      aneurysmal neck. Complete occlusion was obtained in 85% of superior hypophyseal
      aneurysms of the paraclinoid variant. One permanent complication was related to
      treatment. CONCLUSION: Endovascular treatment with GDCs appears to be a safe and
      efficient alternative approach for ophthalmic segment aneurysms, especially for
      paraclinoid variants of superior hypophyseal aneurysms, which tend to have a
      small neck.

PMID- 9282844
TI  - Dissecting aneurysms of all four cervicocranial arteries in fibromuscular
      dysplasia: treatment with self-expanding endovascular stents, coil embolization,
      and surgical ligation.
AB  - A patient with cervicocranial fibromuscular dysplasia (FMD) presented with
      subarachnoid hemorrhage. A ruptured dissecting distal vertebral artery aneurysm
      required clip ligation of the parent artery; a contralateral dissecting proximal
      vertebral aneurysm was occluded with detachable coils. Progressive dissecting,
      extracranial aneurysms of the internal carotid artery were treated with self
      expanding stents. Subsequent angiography and intravascular sonography revealed
      patent stents, a smooth luminal surface, and total occlusion of the aneurysm.
      Clinical outcome was excellent.

PMID- 9282845
TI  - Relationship between clot location and outcome after basilar artery thrombolysis.
AB  - PURPOSE: To identify factors that predict survival and good neurologic outcome in
      patients undergoing basilar artery thrombolysis. METHODS: Over a 42-month period,
      20 of 22 consecutive patients with angiographic proof of basilar artery
      thrombosis were treated with local intraarterial urokinase. Brain CT scans,
      neurologic examinations, symptom duration, clot location, and degree of
      recanalization were analyzed retrospectively. RESULTS: Overall survival was 35%
      at 3 months. Survival in patients with only distal basilar clot was 71%, while
      survival in patients with proximal or midbasilar clot was only 15%. At 3 months,
      29% of patients with distal basilar clot and 15% of patients with proximal or
      midbasilar clot had good neurologic outcomes (modified Rankin score of 0 to 2 and
      Barthel index of 95 to 100). Complete recanalization was achieved in 50% of
      patients; 60% of those survived and 30% had good neurologic outcomes. Of patients
      with less than complete recanalization, only 10% survived. Neither duration of
      symptoms before treatment (range, 1 to 79 hours), age (range, 12 to 83 years),
      nor neurologic status at the initiation of treatment (Glasgow Coma Scale score
      range, 3 to 15) predicted outcome. Pretreatment CT findings (positive or negative
      for related ischemic changes) did not predict outcome or hemorrhagic
      transformation. CONCLUSION: The single best predictor of survival after basilar
      thrombosis and intraarterial thrombolysis was distal clot location. Complete
      recanalization favored survival. Radiologically evident related infarctions,
      advanced age, delayed diagnosis, and poor pretreatment neurologic status did not
      predict poor outcome and therefore should not be considered absolute
      contraindications for intraarterial thrombolysis in patients with basilar artery
      thrombosis.

PMID- 9282846
TI  - Arteriovenous malformation model for training and research.
AB  - PURPOSE: To develop an arteriovenous malformation (AVM) model for teaching
      embolization techniques and for researching and developing new interventional
      devices. METHODS: Open pore cellulose sponges 2 to 5 cm in diameter were coated
      with a watertight elastomer. One to three afferent tubes (arteries) and one large
      efferent tube (vein) allowed insertion of the model into a circuit of pulsatile,
      flowing, non-Newtonian fluid. Using fluoroscopy and angiographic imaging, five
      neuroradiologists practiced occluding the AVM nidus with a variety of techniques
      and cyanoacrylate mixtures. RESULTS: The model appeared and behaved like a human
      brain AVM. Attempts to teach liquid adhesive techniques were successful, and
      though they were stressful for the trainee, failure had none of the disastrous
      sequelae that attend training with human subjects. CONCLUSION: The AVM training
      and research model is of value in introducing physicians to the techniques needed
      for endovascular cyanoacrylate therapy: it allows users to develop skills at
      their own rates, and permits safe "failure-mode" learning.

PMID- 9282847
TI  - Embolization of cerebral arteriovenous malformations with silk: histopathologic
      changes and hemorrhagic complications.
AB  - PURPOSE: To evaluate the safety of silk as an embolic agent for preoperative
      embolization of cerebral arteriovenous malformations (AVMs) by assessing the
      histopathologic changes and hemorrhagic complications associated with its use.
      METHODS: Histopathologic specimens, medical records, and radiologic records of 73
      patients with AVMs embolized with silk (alone or in combination with other
      agents) were reviewed retrospectively. Forty-eight histologic specimens obtained
      at surgery were analyzed for inflammatory responses and compared with the time
      interval between embolization and surgery. Postembolization angiograms were
      assessed for vasculitis and CT scans were reviewed for evidence of hemorrhage
      after embolization. RESULTS: There was no angiographic evidence of vasculitis.
      Histologic evidence of vasculitis was absent or mild in 92% of cases and
      histologic evidence of perivascular inflammation was absent or mild in 73% of
      cases. The frequency of histologic changes associated with vasculitis,
      perivascular inflammation, and vessel necrosis varied with the time interval
      between embolization and AVM resection. Intracranial hemorrhage, as a direct
      complication of silk use, occurred in one patient. Another patient had
      subarachnoid hemorrhage 24 hours after embolization, caused by rupture of a
      posteroinferior cerebellar artery aneurysm. Intraventricular high-density
      material appeared on routine postembolization CT scans in two other patients who
      had intraventricular AVM extension. This high-density material was thought to be
      contrast extravasation from intrinsically leaky AVM nidus vessels and not frank
      hemorrhage. CONCLUSION: Embolization of AVMs with silk does not result in marked
      inflammation or increased hemorrhagic complications as compared with other
      agents.

PMID- 9282848
TI  - Direct thrombolysis of superior sagittal sinus thrombosis with coexisting
      intracranial hemorrhage.
AB  - We present a case of dural cerebral venous thrombosis with coexisting left
      frontal hemorrhage that was successfully treated with 13.79 million units of
      urokinase over a period of 165 hours.

PMID- 9282849
TI  - Thrombogenicity of hydrophilic and nonhydrophilic microcatheters and guiding
      catheters.
AB  - PURPOSE: To assess in a swine model the in vivo thrombogenicity of various
      microcatheters and guiding catheters as a function of catheter material, catheter
      coating, and duration of implantation. METHODS: Microcatheters (Tracker 18 and
      Fastracker 18, Target Therapeutics, Fremont, Calif; Magic 1.8, Balt, Montmorency,
      France; and Transit, Cordis Endovascular Systems, Miami Lakes, Fla) were placed
      through 6F guiding catheters (Fasguide, Target Therapeutics, and Envoy, Cordis
      Endovascular Systems) into the common carotid arteries of swine for 30 minutes
      (short term), 90 minutes (medium term), and 35 days (long term). Guiding
      catheters were implanted for 5 hours. At the end of the implantation periods the
      catheters were retracted and fixed for scanning electron microscopy. RESULTS: The
      surface of the Fastracker microcatheter was devoid of debris after both short-
      and medium-term implantation. The Tracker microcatheter had minimal accumulation
      of cellular elements whereas the Transit microcatheter showed moderate
      accumulation of nondeformed red blood cells. Neither the Tracker nor the Transit
      microcatheter showed evidence of increasing debris accumulation after medium-term
      implantation as compared with short-term implantation. The Magic microcatheter
      was coated with gross thrombus after both short- and medium-term implantation.
      The Fasguide guiding catheter was nearly devoid of debris, while the Envoy
      guiding catheter had moderate thrombus formation. Long-term implantation of the
      Fastracker microcatheter was well tolerated whereas that of the Transit catheter
      resulted in vessel occlusion. CONCLUSIONS: Hydrophilic microcatheters and guiding
      catheters are less thrombogenic than their nonhydrophilic counterparts, but not
      all hydrophilic coatings are equally hypothrombogenic. Degree of thrombogenicity
      depends on catheter material rather than surface morphology. Medium-term
      implantation did not yield increasing thrombus formation relative to short-term
      implantation.

PMID- 9282850
TI  - Preoperative embolization of anastomoses of the jugular bulb: an adjuvant in
      jugular foramen surgery.
AB  - We describe the technique of preoperative embolization of the inferior petrosal
      sinus/anterior condylar vein complex and the posterior condylar vein in three
      patients undergoing skull base surgery that required opening of the jugular bulb.
      Contrary to the usual situation, essentially no blood was lost during the
      operation, resulting in decreased surgical time and reduced risk to the lower
      cranial nerves.

PMID- 9282851
TI  - Basilar artery rethrombosis: successful treatment with platelet glycoprotein
      IIB/IIIA receptor inhibitor.
AB  - We describe the use of abciximab to prevent rethrombosis of the basilar artery
      after transluminal angioplasty. A 60-year-old patient with vertebral basilar
      insufficiency and acute occlusion of the basilar artery underwent
      revascularization with urokinase and angioplasty. Despite the repeated use of
      urokinase and angioplasty under anticoagulation with heparin, the basilar artery
      immediately rethrombosed. In a final attempt to prevent rethrombosis, abciximab
      was administered before the final angioplasty, resulting in a widely patent
      basilar artery and no rethrombosis.

PMID- 9282852
TI  - Posttraumatic extracranial aneurysm of the internal carotid artery: combined
      endovascular treatment with coils and stents.
AB  - We report a case of a posttraumatic extracranial pseudoaneurysm of the internal
      carotid artery that was treated successfully via embolization with Guglielmi
      detachable coils and placement of a Wallstent after surgical repair failed.

PMID- 9282854
TI  - Neurometabolism of active neuropsychiatric lupus determined with proton MR
      spectroscopy.
AB  - PURPOSE: To determine the neurometabolism of patients with active
      neuropsychiatric systemic lupus erythematosus (NPSLE) by using proton MR
      spectroscopy. METHODS: Thirty-six patients with SLE and eight control subjects
      were studied with proton MR spectroscopy to measure brain metabolites. Peaks from
      N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and at 1.3 parts per
      million (ppm) lipid, macromolecules, and lactate were measured. Patients were
      classified as having major NPSLE (seizures, psychosis, major cognitive
      dysfunction, delirium, stroke, or coma) (n = 15) or minor NPSLE (headache, minor
      affective disorder, or minor cognitive disorder) (n = 21). Patients with major
      NPSLE were severely ill and hospitalized. RESULTS: SLE patients had lower NAA and
      increased metabolites at 1.3 ppm than did control subjects (NAA/Cr(SLE) = 1.90 +/
      0.35, NAA/Cr(Control) = 2.16 +/- 0.26; 1.3 ppm/Cr(SLE) = 0.49 +/- 0.41, 1.3
      ppm/Cr(Control) = 0.27 +/- 0.05). NAA/Cr in patients with current or prior major
      NPSLE was lower than in patients without major NPSLE. Increased peaks at 1.3 ppm
      were present in all SLE subgroups, but particularly in patients with major NPSLE.
      These resonances were not evident at an echo time of 136, indicating that these
      signals were not lactate. CONCLUSION: Major NPSLE, past or present, is associated
      with decreased levels of NAA. Elevated peaks around 1.3 ppm do not represent
      lactate even in severely ill patients, indicating that global ischemia is not
      characteristic of NPSLE. Neurochemical markers determined by MR spectroscopy may
      be useful for determining activity and degree of brain injury in NPSLE.

PMID- 9282853
TI  - Brain MR in chronic fatigue syndrome.
AB  - PURPOSE: To determine the prevalence of MR white matter abnormalities in patients
      with chronic fatigue syndrome (CFS). METHODS: Brain MR studies of 43 patients (29
      women and 14 men, 22 to 78 years old) with a clinical diagnosis of CFS (n = 15),
      CFS with associated depression (n = 14), and CFS with associated other
      psychiatric disorders, namely, anxiety and somatization disorder (n = 14), were
      compared with brain MR studies in 43 age- and sex-matched control subjects.
      RESULTS: MR findings were abnormal in 13 (32%) of the patients in the study group
      (ages 34 to 78 years) and in 12 (28%) of the control subjects (ages 26 to 73
      years). One patient with CFS had multiple areas of demyelination in the
      supratentorial periventricular white matter. Another patient with CFS and
      associated depression had a single focus of probable demyelination in the
      supratentorial periventricular white matter. In four patients with CFS (ages 34
      to 48 years) MR abnormalities consisted of one or several punctate hyperintense
      foci in the corona radiata, centrum ovale, and frontal white matter. The
      remaining seven patients (ages 50 to 78 years) had frontoparietal subcortical
      white matter foci of high T2 signal. The prevalence of white matter
      hyperintensities was not different between the patients and the control subjects.
      CONCLUSIONS: Our findings suggest that no MR pattern of white matter
      abnormalities is specific to CFS.

PMID- 9282855
TI  - Single-dose gadolinium with magnetization transfer versus triple-dose gadolinium
      in the MR detection of multiple sclerosis lesions.
AB  - PURPOSE: To compare the efficacy of single-dose gadolinium with magnetization
      transfer contrast (MTC) with that of triple-dose gadolinium in detecting
      enhancing multiple sclerosis lesions. METHODS: Twenty-one patients with multiple
      sclerosis were examined with MR imaging first with 0.1 mmol/kg gadolinium (single
      dose) and then, after 24 to 72 hours, with 0.3 mmol/kg gadolinium (triple dose).
      T2-weighted fast spin-echo and T1-weighted spin-echo MR images with and without
      MTC were obtained before contrast administration followed by either T1-weighted
      spin-echo images with MTC (single dose) or conventional T1-weighted spin-echo
      images (triple dose), starting 5, 17, and 29 minutes after contrast
      administration. All images were evaluated in a blinded fashion and scored in
      random order by two readers. Outcome parameters included number of enhancing
      lesions, number of active MR examinations (those containing at least one
      enhancing lesion), contrast ratio (signal intensity of enhancing lesion divided
      by signal intensity of normal-appearing white matter), and size of enhancing
      lesions. RESULTS: Eighty-one percent more enhancing lesions and 49% more active
      MR examinations were detected when a triple dose of gadolinium was used as
      compared with a single dose. The level of agreement between readers as to the
      number of enhancing lesions was significantly higher for triple-dose than for
      single-dose gadolinium. With triple-dose gadolinium, contrast ratios and areas of
      enhancement increased by 10% and 33%, respectively. Delayed imaging increased the
      size of the lesion by 11% on single-dose MTC images and by 18% on triple-dose
      images. CONCLUSION: Triple-dose gadolinium is more effective (higher sensitivity
      and interobserver agreement) than single-dose gadolinium in combination with MTC
      in detecting enhancing multiple sclerosis lesions.

PMID- 9282856
TI  - Global volumetric estimation of disease burden in multiple sclerosis based on
      magnetization transfer imaging.
AB  - We report a semiautomated postprocessing method based on magnetization transfer
      MR imaging that can quantify the extent of global disease in patients with
      multiple sclerosis. The technique combines segmentation and quantitative analysis
      of imaging data reflecting the structural integrity of white matter. Applications
      of this technique may include assessment of disease progress and of the efficacy
      of experimental therapeutic intervention. The height of the histogram peak
      corresponding to white matter was found to be lowered in patients with multiple
      sclerosis and the overall distribution of magnetization transfer ratios was
      shifted to lower values.

PMID- 9282858
TI  - Arthur Schuller: pioneer of neuroradiology.

PMID- 9282857
TI  - MR changes in the calcarine area resulting from retinal degeneration.
AB  - PURPOSE: To study MR images for atrophic changes in the calcarine area resulting
      from retinal degeneration. METHODS: MR images from nine patients with retinal
      degeneration confirmed by ophthalmologic examination and from 30 healthy
      volunteers were reviewed. The causes of retinal degeneration were hereditary
      pigmentary degeneration of the retina (four patients), high myopia (two
      patients), and chorioretinal atrophy (three patients); all patients had visual
      disturbances and visual field abnormalities. To estimate the morphological
      changes of the calcarine area, the widths of the right and left calcarine
      fissures were measured on T1-weighted sagittal images and compared with images
      from age-matched control subjects. RESULTS: The calcarine fissures were
      significantly dilated in the patients with retinal degeneration. The anterior and
      middle points, which represent the peripheral visual field center, were more
      dilated than the posterior point. CONCLUSION: The MR findings suggested calcarine
      atrophy related to retinal degeneration. Transneuronal degenerative changes may
      occur in the calcarine area after retinal degeneration.

PMID- 9282859
TI  - Disseminated miliary cerebral candidiasis.
AB  - We present a case of disseminated intracranial infection by Candida albicans in a
      5-year-old girl who had fever and a change of consciousness after surgery for
      complex congenital heart malformation. MR imaging revealed multiple small ring
      enhancing hemorrhagic abscesses. One year after antifungal treatment, the
      abscesses and ventriculomegaly were almost completely resolved. The patient was
      discharged in a stable but vegetative condition.

PMID- 9282860
TI  - Inflammatory pseudotumor of the choroid plexus.
AB  - A case of inflammatory pseudotumor is described, in which CT revealed a
      hyperdense intraventricular lesion with a trapped temporal horn, and MR imaging
      showed decreased T1 and markedly hypointense T2 signal with homogeneously intense
      enhancement. Radiologically and grossly the tumor resembled a meningioma;
      however, histologically it was composed purely of inflammatory, nonneoplastic
      components. The lesion was resected with no evidence of recurrence at 5-month
      follow-up.

PMID- 9282863
TI  - How to review and retrieve information from the AJNR; or, how to read the AJNR
      and still have time to ski.

PMID- 9282861
TI  - Functional MR activation correlated with intraoperative cortical mapping.
AB  - PURPOSE: To evaluate the spatial specificity of functional MR imaging by
      comparing it with intraoperative electrocortical mapping. METHODS: Functional MR
      imaging was performed in 28 patients before awake craniotomy and intraoperative
      electrocortical mapping. Activation was mapped for finger movement, lip movement,
      tongue movement, word generation, and counting paradigms. During surgery, finger
      movement, lip movement, tongue movement, counting, and/or speaking were mapped.
      The functional images and the photographic recordings of the brain functions
      mapped during surgery were converted to bit maps and coregistered by a computer
      program. The distance between the intraoperatively mapped function site and the
      MR activation site for a comparable function was measured. RESULTS: Forty-six
      functions were recorded on MR images and intraoperative maps. In 100% of
      correlations, the intraoperative site and the MR activation site were within 20
      mm; in 87% of correlations they were within 10 mm. For each paradigm, 67% or more
      of the intraoperative stimulation maps correlated within 10 mm of the MR
      activation site. CONCLUSIONS: For the tasks used in this study, the activation
      site on functional MR images correlated well with the site at which
      intraoperative stimulation identified function.

PMID- 9282862
TI  - Test-retest analysis with functional MR of the activated area in the human visual
      cortex.
AB  - PURPOSE: To investigate the intersubject and intrasubject variability of the
      activated area in the visual cortex with functional MR imaging. METHODS: Double
      section gradient-echo MR images were acquired at 1.5 T in 28 healthy volunteers
      using the fast low-angle shot (FLASH) technique. Visual stimulation was obtained
      with light-emitting diode (LED) goggles. Eighteen volunteers were studied twice.
      The size of the activated areas in the visual cortex and the increase in signal
      were measured. A reproducibility ratio for size (R[size]) and for location
      (R[overlap]) was calculated on a scale of 0.0 to 1.0. RESULTS: Activation was
      seen in 89% of the subjects. The size of the activated area was widely variable
      among subjects: mean, 460 +/- 284 mm2; range, 0 to 1029 mm2 in the first study in
      all volunteers. Signal increases ranged from 3.2% to 10.9%, with a mean of 6.6 +/
      1.7%. The mean values of intrasubject variability testing were R(size) = 0.83 +/
      0.16 and R(overlap) = 0.31 +/- 0.11. CONCLUSION: Functional MR imaging with the
      FLASH technique is useful in identifying certain cortical areas that have quite
      variable locations among subjects. This study provides reference data for the
      intrasubject and intersubject variability of the activation pattern of the visual
      cortex.

PMID- 9282864
TI  - Lumbar facet joint tropism does not accelerate degeneration of the facet joints.
AB  - PURPOSE: To study the relationship of lumbar facet joint tropism to degeneration
      of the cartilage and subcortical bone in the facet joints and the effect of
      tropism in intervertebral disk degeneration. METHODS: The orientation of 104
      cadaveric lumbar facet joints with respect to sagittal plane was measured on CT
      scans, and the joints were classified as having no tropism, mild tropism, or
      severe tropism. On MR images, the severity of cartilage degeneration and bony
      sclerosis was measured. The correlation between tropism and degeneration was
      calculated, as was the relationship among age, spinal level, and degeneration.
      RESULTS: We identified four spinal levels with severe tropism, six with moderate
      tropism, and 94 without tropism. Cartilage degeneration was not significantly
      more severe in the joints with tropism than in the joints without. Sclerosis was
      slightly greater in the joints with tropism than in the joints without it.
      Sclerosis and cartilage degeneration were significantly related to age and spinal
      level. CONCLUSION: Age, spinal level, and overall facet joint angle are more
      important factors in facet joint degeneration than is tropism.

PMID- 9282865
TI  - Cervical myelopathy associated with intracranial dural arteriovenous fistula: MR
      findings before and after treatment.
AB  - The MR findings in three patients with intracranial dural arteriovenous fistula
      associated with cervical myelopathy are described. The MR appearance of an
      enlarged cord with associated abnormal signal and enhancement is nonspecific and
      can simulate tumor, demyelination, and inflammation. Enlarged perimedullary
      vessels may not always be identifiable, but if present, should suggest the
      presence of an arteriovenous fistula.

PMID- 9282866
TI  - Ectopic extraspinal meningioma: CT and MR appearance.
AB  - We report a case of an ectopic, extraspinal meningioma that appeared as a midline
      interscapular mass in a 13-year-old girl. The tumor involved the T-2 and T-3
      spinous processes, but was dorsal to the lamina and was entirely extrinsic to the
      spinal canal. Large amounts of tumoral calcification and reactive hyperostosis
      were present, radiologically mimicking an osteogenic sarcoma.

PMID- 9282868
TI  - Extraneous lipid contamination in single-volume proton MR spectroscopy: phantom
      and human studies.
AB  - PURPOSE: To determine the degree of extraneous lipid contamination in defined
      volumes of interest studied with single-volume proton MR spectroscopy. METHODS:
      Single-volume proton MR spectroscopy was performed on a fat/water phantom and in
      three volunteers using the stimulated-echo acquisition mode (STEAM) and point
      resolved spectroscopy (PRESS) localization methods. Three different volumes of
      interest (8, 27, and 64 cm3) were examined at echo times of 20, 135, and 270 for
      the STEAM sequences and 135 and 270 for the PRESS acquisitions in both the
      phantom and the volunteers (volumes of interest were placed adjacent to but not
      encompassing fat-containing structures, such as the scalp and retroorbital fat).
      The degree of lipid contamination was then correlated with measurements of the
      section profiles. RESULTS: The PRESS method resulted in less extraneous lipid
      contamination in both phantom and volunteer studies. The STEAM method had the
      highest level of lipid contamination signal in phantom and human studies. In the
      volunteers, volumes of interest abutting fat-containing structures obtained with
      PRESS or STEAM sequences showed no lipid contamination. However, the STEAM
      sequences showed lipid signal in the volume of interest adjacent to orbital fat
      whereas the PRESS sequences did not. These observations are supported by the
      section profile studies, which showed that the actual volume excited by the STEAM
      sequence was 7% to 32% larger than that originally selected, while with PRESS the
      actual excited volume was 12% to 16% smaller than that originally selected.
      CONCLUSION: In our MR unit, short-echo-time STEAM sequences (< or = 135
      milliseconds) resulted in extraneous lipid contamination in phantom and human
      studies adjacent to the orbits. PRESS sequences showed no lipid contamination in
      volumes abutting fat structures in phantoms or humans. These results correlated
      closely with the configuration of the section profiles. Although these findings
      might be dependent on the MR unit used, our study could help determine extraneous
      lipid contamination for other MR units.

PMID- 9282867
TI  - Segmented three-dimensional echo-planar flow imaging of the cervical carotid
      arteries.
AB  - PURPOSE: To implement and assess the application of segmented three-dimensional
      echo-planar MR imaging time-of-flight flow sequences for studying the anatomy of
      the cervical carotid arteries at 1.5 T. METHODS: The 3-D echo-planar sequences
      were segmented along the in-plane phase-encoding direction. Echo train lengths
      (ETLs) of 3 and 5 and signal bandwidths of +/-25, +/-33, and +/-50 KHz were
      tested along with a conventional (ETL = 1) 3-D MR flow study in six healthy
      volunteers and in five patients with known arteriosclerotic disease involving the
      carotid bifurcation as confirmed by conventional angiography. The volunteer data
      were used to rank the techniques with respect to vessel dimension,
      vessel/background contrast, and quality by four trained neuroradiologists. For
      the patient studies, the percentage of stenoses was measured for all MR studies
      and compared against the conventional angiographic data using the criteria of the
      North American Symptomatic Carotid Endarterectomy Trial. RESULTS: Using
      Wilcoxon's test statistic and a significance level of .05, we found that the
      conventional MR flow examination was better than the segmented techniques and
      that the segmented techniques with ETL of 3 were superior to their counterparts
      with ETL of 5. For the ETL of 3 techniques, the high-bandwidth studies were
      inferior to their lower bandwidth counterparts; however, there was no significant
      difference between the performance of the medium- and low-bandwidth sequences.
      The patient data revealed that the segmented techniques consistently
      overestimated the severity of stenosis; however, in no instance did any of the
      segmented examinations erroneously indicate the presence of disease. CONCLUSIONS:
      The reduction in acquisition time and the zero false-positive rate we obtained
      suggest that segmented 3-D echo-planar MR flow techniques may be used as a
      screening/locating study for cervical carotid artery disease.

PMID- 9282869
TI  - MR of epidermoids with a variety of pulse sequences.
AB  - PURPOSE: To assess the usefulness of fluid-attenuated inversion recovery (FLAIR)
      and constructive interference in steady state (CISS) sequences in depicting
      epidermoid tumors. METHODS: Six patients with surgically confirmed epidermoid
      tumors in the subarachnoid space were examined with T1-weighted MR imaging with a
      spin-echo sequence, and with T2- and proton density-weighted imaging with a fast
      spin-echo sequence, a FLAIR sequence, and a CISS sequence. In the qualitative
      analysis, three observers compared the five sequences for visibility of tumors
      and presence of artifacts. A quantitative analysis was also performed by
      measuring the contrast-to-noise ratio. RESULTS: On visual assessment, the FLAIR
      sequence depicted all tumors as hyperintense relative to cerebrospinal fluid. The
      CISS sequence depicted all tumors as hypointense relative to cerebrospinal fluid
      and was considered to show tumor extension better than the FLAIR sequence. At
      quantitative analysis, the mean contrast-to-noise ratios of tumor to
      cerebrospinal fluid on T1-, T2-, and proton density-weighted images, and on FLAIR
      and CISS sequences were 2.85, 3.41, 4.42, 16.13, and 20.23, respectively. The
      contrast-to-noise ratios for the FLAIR and CISS sequences were significantly
      higher than those for the T1-, T2-, and proton density-weighted sequences. The
      contrast-to-noise ratio was not significantly different between FLAIR and CISS
      sequences, although the CISS sequence was slightly superior. CONCLUSION: CISS and
      FLAIR sequences depicted epidermoid tumors in the subarachnoid spaces better than
      conventional spin-echo images did. The CISS sequence produced a relatively
      constant contrast between the tumors and less artifactual interference.

PMID- 9282871
TI  - Cystlike white matter lesions in tuberous sclerosis.
AB  - PURPOSE: To investigate the presence of small cystlike structures in the cerebral
      hemispheric white matter on MR images of patients with tuberous sclerosis.
      METHODS: The MR images of 18 consecutive patients with tuberous sclerosis were
      reviewed retrospectively. RESULTS: Eight of the 18 patients were found to have
      cystlike structures in the cerebral white matter. The signal intensity of these
      lesions was isointense with cerebrospinal fluid on T1-, proton density-, and T2
      weighted images. Four patients were imaged with a fluid-attenuated inversion
      recovery sequence, which in each case also showed fluid-type signal in these
      areas. Three of the patients had CT for correlation, and these scans supported
      the diagnosis of cystic lesions. Cysts ranged in number from one to 12 per
      patient and were usually smaller than 1 cm. The most common location was adjacent
      to the occipital horn or trigone of the lateral ventricle (six of eight
      patients). Less frequent sites were near the frontal horns, in the corpus
      callosum, and in the deep white matter near the body of the lateral ventricle.
      Cysts in five patients were either immediately adjacent to a cortical tuber or in
      the center of a white matter dysplastic lesion. A cyst in one patient had septa,
      and none of the cysts enhanced. CONCLUSIONS: Cystlike structures in the cerebral
      hemispheric white matter were seen on the MR images of 44% of 18 patients with
      tuberous sclerosis. Whether these findings represent cystic degeneration of
      dysplastic tissue or are unrelated to the disease process of tuberous sclerosis
      is unknown. More than one pathogenesis may exist.

PMID- 9282870
TI  - Desmoplastic medulloblastoma: MR findings.
AB  - In three cases of desmoplastic medulloblastoma, MR findings were varied. We
      report the unusual appearance of this tumor in two children and one adult.

PMID- 9282872
TI  - MR appearance of trigeminal and hypoglossal motor denervation.
AB  - PURPOSE: To illustrate and describe the appearance of both long-standing and
      relatively recently occurring motor denervation of the hypoglossal nerve and of
      the third (mandibular) division of the trigeminal nerve (V3), with emphasis on
      findings particular to MR imaging. METHODS: Findings from 11 patients with V3
      denervation and from seven patients with hypoglossal denervation resulting from a
      variety of abnormalities were reviewed retrospectively. The motor denervation
      appearance and functional compromise of the affected musculature are described in
      terms of the chronicity of the denervation process. RESULTS: The appearance of V3
      and hypoglossal motor denervation varies with the chronicity of the process. Long
      standing denervation results in extensive fatty replacement and a decrease in the
      size of the affected musculature. Relatively recently occurring denervation
      results in abnormal contrast enhancement and edemalike signal changes in the
      denervated musculature. Fatty replacement was observed acutely in hypoglossal
      denervation but did not manifest until the subacute stage in V3 denervation.
      Increased volume of the denervated musculature may also accompany acute
      denervation signal changes. CONCLUSION: V3 and hypoglossal denervation have a
      variable appearance depending on the chronicity of the process. Recognition of MR
      imaging patterns of denervation may allow earlier diagnosis of a denervating
      lesion and may help to distinguish denervation from similar-appearing processes,
      such as infection or neoplasia.

PMID- 9282873
TI  - Vertebrobasilar dolichoectasia: evaluation with CT angiography.
AB  - We present three patients who were admitted to our institution with
      vertebrobasilar dolichoectasia diagnosed at CT angiography. Two patients had
      associated intraarterial thrombi and one patient had basilar artery dissection.
      Shaded surface display images were useful in showing arterial anatomy relative to
      the skull base. Source images and curved-reformatted images were helpful in
      diagnosing thrombi and dissection. CT angiography is a minimally invasive means
      of diagnosing and following up these patients.

PMID- 9282874
TI  - Retrievable versus nonretrievable coils.

PMID- 9282875
TI  - Retrievable versus nonretrievable coils.

PMID- 9282876
TI  - The intravascular mobile structure detected with duplex carotid ultrasound in
      patients with cardioembolic carotid artery occlusion.

PMID- 9282877
TI  - The intravascular mobile structure detected with duplex carotid ultrasound in
      patients with cardioembolic carotid artery occlusion.

PMID- 9282878
TI  - Measuring intraaneurysmal flow: risk of perforation.

PMID- 9282880
TI  - MR techniques for the internal auditory canal.

PMID- 9282879
TI  - Measuring intraaneurysmal flow: risk of perforation.

PMID- 9282881
TI  - MR techniques for the internal auditory canal.

PMID- 9282882
TI  - A plea for proper recognition: the syndrome of Maestre de San Juan-Kallman.

PMID- 9282883
TI  - Annotated bibliography.

PMID- 9282884
TI  - The envelope following response to multiple tone pair stimuli.
AB  - The envelope following response (EFR) is a steady-state evoked response which
      follows the envelope of a stimulating waveform. A tone pair with frequencies f1
      and f2 generates a temporal envelope whose period corresponds to the difference
      in frequency between the constituent tones (f2-f1 = f2,1). EFRs were recorded
      from Mongolian gerbils using amplitude-modulated stimuli comprised of from 1 to 4
      tone pairs. Five stimulus tone pairs were used having center frequencies of
      approximately 0.3, 1, 2, 3, and 5 kHz; their corresponding envelope frequencies
      were approximately 38, 55, 66, 85, and 142 Hz. The magnitude of the EFR to each
      tone pair was measured separately and in combination with other simultaneously
      presented tone pairs. Small decreases (1-3 dB) in response magnitude, relative to
      the single tone pair condition, resulted from the addition of 1-2 tone pairs of
      higher frequencies; this effect was more pronounced with the addition of a third
      and fourth tone pair. However, the addition of the 300 Hz tone pair resulted in
      the significant enhancement of the response to higher frequency tone pairs. These
      data indicate that multiple tone pair EFRs may be a useful technique for the
      rapid acquisition of frequency-specific audiometric information.

PMID- 9282885
TI  - Discrimination of rippled-spectrum noise from flat-spectrum noise by chinchillas:
      evidence for a spectral dominance region.
AB  - Iterated rippled noise having infinite iterations is generated when a flat
      spectrum wideband noise is delayed T ms and the delayed version is added to the
      undelayed noise through positive feedback. The resulting signal has a rippled
      spectrum, and the perceived pitch of this iterated rippled noise by human
      listeners corresponds to a frequency of 1/T. We have previously demonstrated that
      chinchillas can discriminate the rippled-spectrum noise from the flat-spectrum
      noise. In the present study, chinchillas discriminated a bandpass filtered
      rippled-spectrum noise from a bandpass flat-spectrum noise in a psychophysical
      task. The passbands were set to be one octave wide. Psychometric functions were
      obtained for 5 chinchillas and performance was measured as d'. The best
      behavioral performance was obtained when the center frequency of the bandpass
      filter generally corresponded to the 3rd 5th harmonic peak of the rippled noise
      (i.e., at 3/T to 5/T), but the precise location of the dominant region varied
      with the delay of the rippled noise such that the dominance region tended to
      shift to lower harmonics as 1/T increased. These results indicate that not all
      spectral regions are weighted equally in the discrimination task. The spectral
      dominance region found in chinchillas is similar to that described for human
      pitch perception.

PMID- 9282886
TI  - The effects of anesthesia on otoacoustic emissions.
AB  - We have measured transient-evoked and distortion-product otoacoustic emissions
      (OAEs) in the chinchilla and compared them in the awake and anesthetized animal
      (using either ketamine or barbiturate agents). We report a significant increase
      in OAE amplitudes during anesthesia, particularly using ketamine. These effects
      are most evident for transient-evoked otoacoustic emissions (TEOAEs) as measured
      in the non-linear mode. Our data support the hypothesis that tonic activity
      levels in cochlear efferents may be reduced by anesthetic effects, either
      directly or indirectly (e.g., by general reductions in descending pathway
      activity), and that reduced cochlear efferent activity will result in the
      observed increase of OAE amplitudes.

PMID- 9282888
TI  - Organization and connections of octaval and lateral line centers in the medulla
      of a clupeid, Dorosoma cepedianum.
AB  - In the clupeid fishes, the functionally specialized utricle and cephalic lateral
      line respond to sound pressure by virtue of their mechanical coupling to the
      auditory bullae. The cytoarchitecture of, and primary inputs to, the
      octavolateralis area were studied in the gizzard shad, Dorosoma cepedianum, in
      order to determine whether first-order acoustic and lateral line areas of the
      medulla are likewise specialized. The octavolateralis area of Dorosoma is
      composed of the nuclei that have been observed in other teleosts: nucleus
      medialis, the descending and anterior octaval nuclei, nucleus magnocellularis,
      nucleus tangentialis, and a caudal granular-cell region that likely represents
      nucleus caudalis and the posterior octaval nucleus. The descending octaval
      nucleus can be divided into dorsomedial, intermediate, and ventral zones using
      cytoarchitectonic criteria, whereas the anterior octaval nucleus can be divided
      into caudal, rostral, and medial portions. Primary inputs to the octavolateralis
      area were determined by means of in vitro application of horseradish peroxidase
      to nerves from the otolithic endorgans of the inner ear and the lateral line
      neuromasts. These primary inputs are generally organized like those of other
      teleosts: the otolithic endorgans supply the posterior, descending,
      magnocellular, and anterior nuclei, whereas the majority of lateral line fibers
      project to nucleus medialis, nucleus caudalis, and to the magnocellular nucleus.
      However, other characteristics of these projections may be unique to clupeids.
      The medial subdivision of the dorsomedial zone of the descending nucleus is
      dominated by a bilateral projection from at least a portion of the utricle, while
      the lateral subdivison of the dorsomedial zone is supplied by the saccule and
      lagena. This pattern is not present in non-clupeid fishes; in many species, the
      saccule has the most dorsomedial projection zone within the descending nucleus.
      In Dorosoma, both lateral line nerves contribute a light, bilateral projection to
      the medial and lateral subdivisions of the dorsomedial zone. The apparently
      specialized, bilateral utricular and lateral line inputs to the dorsomedial zone
      of the descending nucleus may be related to the specialized sensitivity of the
      utricle and the cephalic lateral line to sound pressure. A prominent group of
      neurons, tentatively identified as a secondary octaval population, is also
      described. Like the secondary octaval population of otophysans, the presumed
      secondary octaval population of Dorosoma is composed of a dorsal, fusiform
      region, an intermediate spherical cell region, and a ventral fusiform cell
      region.

PMID- 9282887
TI  - The effects of crossed olivocochlear bundle section on transient evoked
      otoacoustic emissions.
AB  - The purpose of this study was to investigate the effect of sectioning the crossed
      olivocochlear bundle (COCB) on transient evoked otoacoustic emissions (TEOAEs) in
      anesthetized adult chinchillas. Of particular interest is the role of cochlear
      efferents to the outer haircells (OHCs) and how they control mechanisms
      responsible for otoacoustic emissions. Specifically the experiment addressed
      whether a tonic level of inhibitory control is reduced by COCB section. The
      nonlinear component of TEOAEs was measured before and after COCB section.
      Analysis was made of the 1, 2, 3, 4, and 5 kHz frequency components and of the
      total emission, as quantified by fast Fourier transform (FFT) of the raw (time
      domain) response. After COCB section, the amplitude of the total response and of
      the 2, 3, 4, and 5 kHz components increased whereas the amplitude of the 1 kHz
      component decreased. The results indicate that COCB section reduces inhibitory
      control of the OHC mechanisms responsible for nonlinear TEOAE generation. It is
      not clear whether the nerve section eliminates a spontaneous level of activity in
      COCB efferents, or whether it results in the interruption of a stimulus-evoked
      feedback loop.

PMID- 9282889
TI  - Spontaneous otoacoustic emissions in the barn owl.
AB  - Spontaneous otoacoustic emissions (SOAE) were studied in a bird, the barn owl.
      They were found in 79% of the ears investigated, and each emitting ear generated
      on average 1.9 emissions. Their peak sound-pressure levels lay between -5.8 and
      10.3 dB, and their centre frequencies between 2.3 and 10.5 kHz. The SOAE
      originated primarily in the upper quarter of the animal's hearing range, and
      derived from a specialized area previously described as being within an auditory
      fovea. Indeed, 93% of the emissions had centre frequencies above 7.5 kHz. The
      median of the frequency distances between neighbouring SOAE was 406 Hz (0.058
      oct). The 3 dB bandwidth of the emissions depended on their amplitude above the
      noise: for SOAE whose level exceeded 10 dB above the noise floor, the 3 dB
      bandwidths ranged between 4.5 and 11.4 Hz. SOAE frequencies were temperature
      sensitive. Raising the temperature shifted the emissions to higher frequencies,
      and vice versa (the frequency shifted on average 0.039 oct/degrees C). External
      tones could suppress the level of SOAE, an effect that was highly tuned. For SOAE
      with frequencies between 2.5 and 10.5 kHz, the Q(10dB) values of 2 dB iso
      suppression tuning curves (STC) varied from 1.07 to 10.40. The best thresholds of
      2 dB STC were generally below 15 dB SPL.

PMID- 9282890
TI  - Nitrosoglutathione suppresses cochlear potentials and DPOAEs but not outer hair
      cell currents or voltage-dependent capacitance.
AB  - Biochemical and pharmacological evidence support a role for nitric oxide (NO) and
      glutathione (GSH) in the cochlea. GSH combines with NO in tissue to form
      nitrosoglutathione (GSNO) that can act as a storage form for GSH and NO.
      Therefore, we tested GSNO on sound-evoked responses of the cochlea (cochlear
      microphonic, CM; summating potential, SP; compound action potential, CAP; cubic
      distortion product otoacoustic emission, DPOAE), on the endocochlear potential
      (EP), on isolated outer hair cell (OHC) currents and voltage-dependent
      capacitance, and on Deiters' cell currents. In vivo application of GSNO in
      increasing concentrations reversibly reduced low-intensity sound-evoked CAP, SP
      and DPOAEs starting at about 1 mM (CAP) and 3.3 mM (SP, DPOAE). However, even at
      10 mM, GSNO had little effect on the EP. In vitro, salicylate (10 mM) but not
      GSNO (3 and 10 mM) suppressed the early capacitative transients of OHCs. GSNO (3
      and 10 mM) had no effect on the whole cell currents of OHCs or Deiters' cells.
      Results show that GSNO suppresses cochlear function. This suppression may be due
      to an effect of GSNO on the cochlear amplifier. The actions of GSNO were
      different from those of other NO donors; therefore, the effects of GSNO may not
      be mediated by NO. The mechanisms underlying GSNO effects seem to be different
      from those of salicylate.

PMID- 9282891
TI  - Differences in the distribution of responses to ATP and acetylcholine between
      outer hair cells of rat and guinea pig.
AB  - Adenosine 5' triphosphate (ATP) and acetylcholine (ACh) are neurotransmitters
      (ACh) and/or modulators (ATP) in the mammalian cochlea. In guinea pig, it appears
      that both neurotransmitters have a similar response distribution, with larger
      responses being evoked by the ligands in short hair cells compared to long hair
      cells (e.g., Chen et al., 1995b. Noise exposure alters the response of outer hair
      cells to ATP. Hear. Res. 88, 215-221.; Erostegui et al., 1994. In vitro
      pharmacologic characterization of a cholinergic receptor on outer hair cells.
      Hear. Res. 74, 135 147). The purpose of the present study was to test whether the
      distribution of responses to ACh and ATP in the OHCs of rat is the same as guinea
      pig. The ligand-induced current was monitored using the whole-cell configuration
      of the patch-clamp technique. Results show that in guinea pig OHCs, extracellular
      application of 100 microM ATP induced a current response in a majority of the
      same cells that responded to the application of 100 microM ACh. In contrast in
      rat OHCs, 100 microM ATP did not induce a current in the majority of cells that
      responded to the application of 100 microM ACh. N-methyl-glucamine (NMG+)
      substituted for K+ in the pipette solution failed to unmask an ATP-evoked inward
      current in rat OHCs. In addition, no response was produced in rat or guinea pig
      OHCs by adenosine, adenosine 5'-monophosphate (AMP) or adenosine 5'-diphosphate
      (ADP) at 100 microM. Results suggest that in guinea pig ACh-gated channels are
      present on most of the same OHCs that have ATP-gated ion channels, whereas in rat
      ACh-gated ion channels are present without ATP-gated channels on some OHCs.

PMID- 9282892
TI  - Transcripts encoding three types of guanylyl-cyclase-coupled trans-membrane
      receptors in inner ear tissues of guinea pigs.
AB  - The distribution of membrane-bound guanylyl cyclase (GC) transcription in inner
      ear tissues of the guinea pig was addressed by a reverse transcription-PCR
      approach using consensus primers flanking a region of about 630 bp in the
      intracellular domains in the target sequences. Restriction mapping of such
      amplificates obtained from cochlear and vestibular specimens permitted us to
      demonstrate GC-A, GC-B, and GC-C expression by differentiating overall PCR
      signals. This assay indicated that GC-A was expressed in the cochlea and
      vestibular organ. PCR products resulting from transcripts of the GC-B gene were
      obtained at considerably lower abundance than amplificates typical of the GC-A
      gene. The consensus primer approach with subsequent restriction mapping provided
      the opportunity to examine at the same time expression of GC-C in the inner ear
      and revealed the occurrence of GC-C transcripts in both inner ear compartments
      under investigation. The distribution pattern found by analysing the
      intracellular domains of membrane-bound guanylyl cyclases was confirmed by
      demonstrating transcription of the corresponding extracellular receptor domains.
      In addition, single-strand conformation polymorphism analysis of cDNA
      amplificates comprising the catalytic domain of guanylyl cyclases also indicated
      the presence of GC-C expression in the inner ear tissues examined. The GC-C
      transcripts detected in inner ear tissues appeared to correlate with functional
      receptor expression, since the production of cyclic GMP catalyzed by cochlear and
      vestibular specimens was stimulated by 1 microM of heat-stable enterotoxin to 18
      and 80% above basal levels, respectively. Thus, GC-C may be involved in the fluid
      regulation by typical ligands (e.g., the peptide hormone guanylin or the toxins
      causing travellers' diarrhea), not only in the intestine but also in the organs
      responsible for hearing and gravitational orientation.

PMID- 9282893
TI  - Ultrastructural organization of proteoglycans and fibrillar matrix of the
      tectorial membrane.
AB  - The molecular and supramolecular structure of the tectorial membrane (TM) was
      studied by transmission electron microscopy (TEM). Collagen (type A) fibrils in
      the TM were found associated with proteoglycans (PGs) and type B fibrils. Most
      PGs were orthogonally oriented and attached D-periodically to collagen fibrils.
      Computer averaged projections of PG particles and linear aggregates of PGs in
      crystalline arrays, stained with Cuprolinic blue, showed an elongated, electron
      dense structure 50-65 nm in length and 10 nm in width. Image analysis of type B
      fibrils showed that they are constructed of globular domains arranged with a
      periodicity of 12-14 nm. Each globular domain contains two thin 'arms', extended
      in opposite directions, which contact the 'arms' of adjacent fibrils. Numerous
      type B fibrils were found between collagen fibrils. They are attached to adjacent
      collagen fibrils by the 'arms' of their globular domains. An association of type
      B fibrils and PGs with collagen seems to result in the local ordered arrangement
      of the TM matrix. A hypothetical model of the TM matrix supramolecular structure
      is presented.

PMID- 9282894
TI  - Electrical and physiological changes during short-term and chronic electrical
      stimulation of the normal cochlea.
AB  - In the electrical stimulation (ES) of auditory pathways, the type of stimulus and
      the electrode/tissue interface are critical parameters for the safety and
      efficacy of the protocol. In this study the influence of alternate pulses,
      applied between round window and vertex electrodes in chronically implanted
      guinea pigs, and maintained during 1 and 25 daily periods of 2 h (short-term and
      long-term experiments, respectively), was investigated. ES consisted of
      monophasic current pulses of +/- 70 microA and 300 (micro)s in duration at a rate
      of 167/s, with alternate polarity. Compound Action Potential (CAP) audiograms,
      amplitudes and latencies of click-evoked CAPs, amplitudes and latencies of
      electrically-evoked auditory responses (EARs), and electrode impedances, were
      measured periodically outside or during the ES periods. Short-term ES induced no
      change in CAP thresholds, amplitude and latency in response to clicks at 80 dB
      above normal threshold, but induced a slight latency increase and amplitude
      decrease of the EAR, correlated with an exponential decay of the electrode
      impedance. On a long-term basis, CAP audiograms and latencies did not change
      significantly, whereas CAP amplitudes and electrode impedances increased, in
      correlation with each other. In control guinea pigs receiving no ES, the same CAP
      amplitude and impedance changes were observed over the same long-term period. The
      EAR and CAP changes can be explained by a variation of the electrical impedance
      of the electrode/tissue interface. This is possibly due to a change in
      electrolytes around the electrode under the influence of the ES for the short
      term variation, and to an electrode encapsulation by fibrous tissue independent
      of the ES for the long-term change. In itself, and under the conditions of this
      experiment, the ES demonstrated no adverse effects on the auditory function and
      can be safely used for inner-ear exploration.

PMID- 9282895
TI  - Paracellular transport properties of inner ear barriers do not account for
      cisplatin toxicity in the rat.
AB  - The interindividual variability for the ototoxic effect of the antineoplastic
      drug cisplatin has still to be explained. To examine if the variability can be
      related to differences in drug kinetics, the effect of cisplatin on the
      paracellular transport properties of the inner ear barriers was studied in vivo
      in cisplatin treated Long-Evans rats. The concentration of [3H]mannitol was
      followed in plasma, scala vestibuli perilymph, and endolymph after an intravenous
      infusion of the tracer. Cisplatin had no effect on paracellular transport of the
      inner ear barriers 3 days after administration of 8 mg/kg cisplatin. However, an
      interindividual variability for the transport of [3H]mannitol across the blood
      perilymph barrier was evident, indicating a variability for the passive transport
      of solutes to the inner ear.

PMID- 9282896
TI  - Immunolocalization of anion exchanger 2alpha in auditory sensory hair cells.
AB  - We have previously reported the isolation from a guinea pig organ of Corti cDNA
      library of a cDNA clone that encodes a novel isoform of the anion exchanger 2
      (AE2) protein (Negrini, Rivolta, Kalinec and Kachar, 1995. Cloning of an organ of
      Corti anion exchanger 2 isoform with a truncated C-terminal domain. Biophys.
      Acta, 1236, 207-211). The deduced protein, named AE2alpha, has a conserved
      cytoplasmic domain and a short membrane domain with only two membrane spanning
      regions, as opposed to the fourteen present in the conventional AE2. Now, we are
      showing the immunolocalization and preliminary characterization of this protein
      using an antipeptide antibody specific for this novel AE2 isoform. In Western
      blots, this antibody binds to an approximately 89 kDa polypeptide that
      corresponds to a phosphorylated protein with serines as main phosphate acceptor
      residues. In immunofluorescence experiments, the antibody labels the stereocilia
      and the lateral wall of the outer hair cells and the stereocilia of the inner
      hair cells. Our results suggest that AE2alpha is a membrane-cytoskeletal linker
      in regions of the hair cell, where sensory transduction mechanisms take place.

PMID- 9282897
TI  - Temporal bone analysis of patients with presbycusis reveals high frequency of
      mitochondrial mutations.
AB  - Presbycusis is a histologically and genetically heterogenous group of disorders,
      which lead to progressive, primarily sensorineural hearing loss with aging.
      Acquired mitochondrial DNA defects have been proposed as important determinants
      of aging, particularly in neuro-muscular tissues. The spiral ganglion and
      membranous labyrinth from archival temporal bones of 5 patients with presbycusis
      were examined for mutations within the mitochondrially-encoded cytochrome oxidase
      II gene. When compared to controls, results indicate that mitochondrial mutations
      in the peripheral auditory system occur commonly with age-related hearing loss,
      that there is great individual variability in both quantity and location of
      mutation accumulation, and that at least a proportion of presbycusis patients
      have a highly significant load of mutations in auditory tissue. This work
      supports the hypothesis that acquired mitochondrial mutations are a determinant
      of hearing loss in a subgroup of presbycusis patients.

PMID- 9282898
TI  - Glycinergic and GABAergic inputs affect short-term suppression in the cochlear
      nucleus.
AB  - Most cochlear nucleus (CN) neurons exhibit short-term response suppression to a
      second stimulus in a paired-pulse (click), forward-masking, paradigm. The
      magnitude of suppression, which appears to be greater than that observed in
      acoustic nerve, is dependent on the temporal separation and/or relative
      intensities of the two stimuli. Recent evidence suggests that inhibitory
      circuitry ending on CN neurons may mediate this response suppression. Using
      extracellular recordings from single CN neurons, suppression was evaluated using
      a forward-masking paradigm. Responses to paired acoustic clicks (i.e., a 'masker'
      followed by an identical 'probe' click) were measured while the time interval
      between the masker and probe was varied systematically. The role of inhibitory
      circuitry in forward-masking in the CN was assessed by pharmacologic manipulation
      of the GABA(A) and glycine(I) (strychnine-sensitive) receptors. Blockade of
      glycinergic or GABAergic receptors by iontophoretic application of the
      antagonists, strychnine and bicuculline methiodide, decreased the effects of
      forward-masking by shortening recovery times of the probe response in 2/3 of the
      neurons tested. Conversely, agonist application (glycine, and GABA or muscimol)
      increased the magnitude of suppression and delayed recovery of the probe response
      relative to control values. These findings suggest that known circuits releasing
      glycine and/or GABA mediate short-term response suppression in some CN neurons.

PMID- 9282899
TI  - Enhanced cochlear responses after sound exposure.
AB  - Alternating potentials produced in Hensen's cells of Mongolian gerbils by
      sinusoidal stimuli were enhanced or depressed after exposure to broad-band sound
      of moderately high intensity, depending on exposure- and stimulus intensities.
      Since Hensen's cell responses have been shown to be identical in phase and
      directly proportional in magnitude to outer hair cell (OHC) responses (Oesterle,
      E.C., Dallos, P., 1989, J. Acoust. Soc. Am. 86 (3), 1013-1032.; Zwislocki, J.J.,
      Slepecky, N.B., Cefaratti, L., Smith, R.L., 1992, Hear. Res. 57, 175-194), it was
      assumed that these changes were reflections of changes in OHC receptor
      potentials, which were of main interest. The indirect method of intracellularly
      recording the Hensen's cell potentials rather than OHC potentials was used to
      minimize damage to the organ of Corti and reduce technical difficulties
      associated with repeated recordings from OHCs. Continuous magnitude and phase
      transfer functions (TFs) were obtained before and after the exposure over a range
      of sound pressure levels (SPLs) extending from 40-90 dB by using frequency sweeps
      ranging from 0.125-18 kHz. Cochlear microphonic (CM) TFs were also acquired over
      the same frequency and intensity ranges for monitoring purposes. The exposure
      stimuli were set at 80, 86, 90 or 100 dB SPL for periods ranging from 10-40 min.
      When response enhancement occurred, it was most clearly seen in the peak of the
      transfer function determined at 90 dB SPL. Enhancement ranged from approximately
      12-230% of the original peak. In contrast, control Hensen's cell recordings
      obtained over periods of up to 130 min revealed great response stability. In all
      reliable recordings, response enhancement was associated with a phase lead or no
      phase change. The strongest exposure stimuli tended to produce sensitivity loss
      accompanied by phase lag at the lower SPLs, in agreement with previous work in
      this laboratory (Zhang and Zwislocki, 1995). In some preparations, both
      sensitivity loss at lower SPLs and enhancement at higher SPLs occurred
      simultaneously, suggesting involvement of two different mechanisms.

PMID- 9282900
TI  - Hyperpolarization-activated current (Ih) in primary auditory neurons.
AB  - A hyperpolarization-activated current (termed I[h]) is believed to provide a
      pacemaker depolarization in sinoatrial node cells and in some central and
      peripheral neurons. In the present study, we examined if such an inward cation
      current exists in primary auditory neurons using the whole-cell patch-clamp
      technique. A large inward, non-inactivating current was seen during
      hyperpolarizing steps negative to the resting potential. A depolarizing sag
      occurred during hyperpolarizing current injection, and upon termination of the
      current injection there was an overshoot, or a rebound firing. A low
      concentration of Cs+, but not Ba2+, reversibly blocked the inward current and
      depolarizing sag. The activation of the current showed voltage dependence with
      half-activation occurring at -101 +/- 1 mV. The time course of I(h) activation
      was fitted by double exponential function and was voltage-dependent (time
      constants: tau1 and tau2 = 480 and 3125 ms at -100 mV, and 66 and 404 ms at -160
      mV). The reversal potential of the current was -36 mV measured from tail
      currents. The conductance of the current was decreased in Na+-free solution, and
      increased in high K+ solution. Increases in the levels of intracellular cAMP or
      cGMP enhanced the current. The results suggest that there exists a
      hyperpolarization-activated inward cation current in mammalian primary auditory
      neurons. This current may provide a depolarizing current during the membrane
      hyperpolarization following each firing of the primary auditory nerve.

PMID- 9282901
TI  - Afferent projection patterns in the auditory brainstem in normal and congenitally
      deaf white cats.
AB  - Cochlear implantation in congenitally deaf children is developing to a successful
      medical tool. Little is known, however, on morphology and pathophysiology of the
      central auditory system in these auditory deprived children. One form of
      congenital hearing loss, that seen in the deaf white cat, was investigated to see
      if there are differences in the afferent pathways from the cochlear nuclei to the
      inferior colliculus. The retrogradely transported fluorescent tracer diamidino
      yellow (DY) was injected into different parts of the central nucleus of the
      inferior colliculus (ICC) of normal cats and deaf white cats. It was found that
      the main afferent projection patterns in deaf white cats were unchanged in spite
      of congenital auditory deprivation; minor differences were seen.

PMID- 9282902
TI  - Immunohistochemical localization of neurocan in the lower auditory nuclei of the
      dog.
AB  - Chondroitin sulfate proteoglycans are present at high levels in the lower
      auditory system of mammals. Axon terminals on the principal neurons in the
      superior olivary nuclei contain chondroitin 4- and 6-sulfate, while the broad
      extracellular matrix around axon terminals contains chondroitin sulfate D, a
      highly sulfated chondroitin sulfate rich in the disaccharide unit of
      GlcA(2S)beta1 --> 3GalNAc(6S), in the dog. In the present study, we investigated
      the immunohistochemical staining of neurocan, a brain-specific proteoglycan, in
      the lower auditory tract of the dog, including an analysis by immunoelectron
      microscopy. Immunolocalization of neurocan was conspicuous in the medial and
      lateral superior olivary nuclei and much less intense immunostaining was seen in
      the cochlear nucleus and posterior colliculus. No immunoreactivity were found in
      other nuclei. The immunostaining in the medial and lateral superior olivary
      nuclei was observed as perineuronal nets around large principal neurons at the
      light-microscopic level, while no immunostaining was observed in the upper
      segment of the medial superior olivary nucleus and the medial segment of the
      lateral superior olivary nucleus, in which medium-sized and small neurons were
      located. Immunoelectron microscopy revealed the reaction products of
      immunostaining on cell membranes of the perikarya of principal neurons and on
      cell membranes of presynaptic terminals which made axo-somatic synapses on the
      principal cells. No immunoreactivity was detected at synaptic junctions, in the
      extracellular matrix or within axon terminals. In the cochlear nucleus,
      immunoreactive perineuronal nets were found around a small number of neurons and
      immunoreactive nerve fibers were scattered in the anterior ventral cochlear
      nucleus. In the posterior colliculus, perineuronal nets, which were weakly
      immunostained, were sparsely distributed in the central nucleus. These results
      suggest that different locations of chondroitin sulfate proteoglycans, including
      neurocan, may be associated with focal sites composed of neuronal surface,
      terminal boutons and extracellular matrix in the lower auditory tract of the
      adult dog.

PMID- 9282903
TI  - Changes in F-actin labeling in the outer hair cell and the Deiters cell in the
      chinchilla cochlea following noise exposure.
AB  - It has been found that 'conditioning' noise exposures can render the inner ear
      more resistant to traumatic noise exposures. To explore the possible mechanisms
      underlying this phenomenon, filamentous actin (F-actin), labeled by rhodamine
      phalloidin, was examined in the chinchilla cochlea using confocal fluorescence
      microscopy. The conditioning noise was 0.5 kHz octave band noise (OBN) at 90 dB
      SPL for 6 h/day and the high-level noise was the same noise but at 105 dB SPL for
      4 h. A variety of pathological changes were found in the chinchilla cochlea after
      exposure to noise. Subjects exposed to conditioning noise (1 day or 10 days) and
      only high-level noise showed an increase in F-actin labeling than unexposed
      controls. By contrast, subjects who had 5 days quiet after the 10-day
      conditioning exposure exhibited a decrease in F-actin labeling. Interestingly,
      subjects exposed to high-level noise with prior 10-day conditioning exposure also
      showed a decrease in F-actin labeling in the cuticular plate and the stereocilia.
      The F-actin decreases in the stereocilia and the cuticular plates may decrease
      the mechanical rigidity of the organ of Corti. A more pliable organ of Corti may
      have reduced the possibility of fracture or ripping of cell junctions during the
      motion of the basilar membrane induced by acoustic overstimulation.

PMID- 9282905
TI  - Total ablation of cochlear haircells by perilymphatic perfusion with water.
AB  - Inner and outer haircells are destroyed within one day following perfusion of the
      perilymphatic spaces with water, otherwise the structural integrity of the
      cochlea and the organ of Corti are preserved. This technique is a reliable method
      to create an acute unilateral deafness model for investigations of auditory
      function.

PMID- 9282904
TI  - NMDA-mediated facilitation in the echo-delay tuned areas of the auditory cortex
      of the mustached bat.
AB  - We recorded the responses of single delay-tuned neurons in the dorsal fringe (DF)
      area and the FM-FM area of the auditory cortex of the mustached bat using multi
      barreled carbon-fiber electrodes. An iontophoretic application of N-methyl-D
      aspartate (NMDA) or kainate (KA) to a DF neuron evoked a burst of discharges from
      the neuron. The burst of discharges evoked by NMDA was always smaller than that
      evoked by KA. Simultaneous application of D-2-Amino-5-phosphonovalerate (APV)
      with NMDA and KA abolished the NMDA-evoked but not the KA-evoked discharges. APV
      did not evoke any significant changes in the auditory responses of 43 out of the
      47 delay-tuned neurons studied in the DF area, and in all 20 neurons studied in
      the FM-FM area. In the remaining four DF neurons, however, APV either increased
      the initial discharges of their auditory response or decreased the late
      discharges of their response. These results indicate that in the majority of
      neurons in the DF and FM-FM areas NMDA receptors do not play a significant role
      in the processing of target-distance information, and that their facilitative
      auditory responses are basically created by synaptic interactions occurring in
      the subcortical auditory nuclei.

PMID- 9282906
TI  - Responses of chopper units in the ventral cochlear nucleus of the anaesthetised
      guinea pig to clicks-in-noise and click trains.
AB  - Auditory brainstem responses (ABRs) have been measured with clicks, clicks masked
      by noise, click trains and pseudorandom maximum length sequences (MLS) of clicks.
      To investigate the neuronal populations contributing to the ABR under these
      stimulation conditions, we measured the extracellular responses of ventral
      cochlear nucleus (VCN) units in the urethane-anaesthetised guinea pig. We studied
      23 chopper, 7 primary-like and 7 onset units. This report focuses on the
      responses from chopper units. The probability of discharge for chopper units
      increased with increasing click level reaching nearly 100% in many units, over a
      range of about 20-30 dB. Following each response to a click there was a 5-10 ms
      suppression of the spontaneous or noise evoked activity. As the level of the
      noise was increased over a range of 20-30 dB, the response to the clicks
      gradually decreased leading to a complete abolition of the click response at high
      noise levels. In a few units, low level noise produced a facilitation of the
      response to single clicks. In response to constant level equally spaced click
      trains, discharge probability increased with increasing minimum pulse interval
      (MPI), approaching 100% for MPIs of 4-8 ms in some units. The recovery afforded
      by the gaps in the MLS train often resulted in higher discharge probability for
      MLS than click trains with the same MPI, while response probabilities for MLS and
      click trains were similar when compared at equivalent average click rates. At
      short MPIs (0.5 and 1.0 ms), peri stimulus time histograms in response to click
      trains resembled those to best frequency (BF) tones and noisebursts, with
      chopping peaks unrelated to unit BF. VCN units show highly synchronised and
      reliable responses to click trains, MLS trains and clicks masked by noise. The
      decrease in discharge rate and increase in latency of chopper units with
      decreasing click level, increasing click rate and increasing masker level
      parallel the peak amplitude and latency changes observed in the auditory
      brainstem response.

PMID- 9282908
TI  - Effects of interaural intensity and time disparity on transient evoked
      otoacoustic emissions.
AB  - Monaural and binaural 11/s, 65 dB pe SPL clicks with interaural time and
      intensity disparities known to affect central auditory processing were used to
      study contralateral suppression of transient evoked otoacoustic emissions
      (TEOAEs) in 10 subjects (20 ears). Psychophysical assessment of sound
      lateralization induced by the same stimuli was also conducted. TEOAEs were
      recorded to monaural (ipsilateral to the OAE recording probe) and to binaural
      clicks when clicks to the contralateral ear were synchronous and symmetrical in
      intensity, or, in the binaural intensity disparity conditions, synchronous but 10
      dB higher or 10 dB lower in the ear contralateral to the OAE recording probe.
      When interaural time disparities were studied, the clicks to the contralateral
      ear were of the same intensity throughout, but 400 micros earlier or 400 micros
      later than to the ear with the probe. The TEOAE components at 13-15.8 ms showed
      suppression, relative to monaural responses, under all binaural conditions. This
      contralateral suppression did not correlate with the psychophysical findings.
      Suppression effects were more pronounced with binaural disparity than with
      binaurally symmetrical clicks. Thus, although contralateral click intensity was
      the same with time disparities, suppression was paradoxically enhanced compared
      to the binaurally symmetrical stimulation. To explain these results we propose
      that two factors are involved in TEOAE suppression with binaural clicks: (1)
      contralateral intensity and (2) interaural disparity (time or intensity). The
      latency of the suppressions observed, the effect of interaural disparity on these
      suppressions, coupled with the anatomical origin of the crossed efferent fibers
      and the disparity sensitivity of the superior olivary complex (SOC), all suggest
      SOC involvement in these TEOAE suppressions.

PMID- 9282909
TI  - Steady state EP is not responsible for hearing loss in adult chickens following
      acoustic trauma.
AB  - The steady state DC endocochlear potential (EP) in young chicks shows a large
      decrease after acoustic overstimulation followed by a rapid recovery that
      parallels the recovery of threshold (Poje et al., Hear. Res. 82 (1995) 197-204).
      These results raise a question as to whether or not the EP could account for the
      hearing loss and make a significant contribution to the recovery of the
      threshold. In contrast to results in young chicks, we show that acoustic
      overstimulation, which causes extensive hair cell damage, does not cause a
      decrease in the steady state EP in adult chickens. However, there is a
      significant reduction in the negative EP seen during anoxia which persists even
      after 4 weeks of recovery. Thus, our results indicate that the steady state EP
      cannot account for the hearing loss observed in adult chickens.

PMID- 9282907
TI  - Calmodulin-dependent protein kinases mediate calcium-induced slow motility of
      mammalian outer hair cells.
AB  - Cochlear outer hair cells in vitro respond to elevation of intracellular calcium
      with slow shape changes over seconds to minutes ('slow motility'). This process
      is blocked by general calmodulin antagonists suggesting the participation of
      calcium/calmodulin-dependent enzymatic reactions. The present study proposes a
      mechanism for these reactions. Length changes of outer hair cells isolated from
      the guinea pig cochlea were induced by exposure to the calcium ionophore
      ionomycin. ATP levels remained unaffected by this treatment ruling out depletion
      of ATP (by activation of calcium-dependent ATPases) as a cause of the observed
      shape changes. Involvement of protein kinases was suggested by the inhibition of
      shape changes by K252a, a broad-spectrum inhibitor of protein kinase activity.
      Furthermore, the inhibitors ML-7 and ML-9 blocked the shape changes at
      concentrations compatible with inhibition of myosin light chain kinase (MLCK). KN
      62, an inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII), also
      attenuated the length changes. Inhibitors with selectivity for cyclic nucleotide
      dependent protein kinases (H-89, staurosporine) were tested to assess potential
      additional contributions by such enzymes. The dose dependence of their action
      supported the notion that the most likely mechanism of slow motility involves
      phosphorylation reactions catalyzed by MLCK or CaMKII or both.

PMID- 9282910
TI  - Phospholipase A2 and its role in brain tissue.
AB  - Phospholipase A2 (PLA2) is the name for the class of lipolytic enzymes that
      hydrolyze the acyl group from the sn-2 position of glycerophospholipids,
      generating free fatty acids and lysophospholipids. The products of the PLA2
      catalyzed reaction can potentially act as second messengers themselves, or be
      further metabolized to eicosanoids, platelet-activating factor, and
      lysophosphatidic acid. All of these are recognized as bioactive lipids that can
      potentially alter many ongoing cellular processes. The presence of PLA2 in the
      central nervous system, accompanied by the relatively large quantity of potential
      substrate, poses an interesting dilemma as to the role PLA2 has during both
      physiologic and pathologic states. Several different PLA2 enzymes exist in brain,
      some of which have been partially characterized. They are classified into two
      subtypes, Ca2+-dependent and Ca2+-independent, based on their catalytic
      dependence on Ca2+. Under physiologic conditions, PLA2 may be involved in
      phospholipid turnover, membrane remodeling, exocytosis, detoxification of
      phospholipid peroxides, and neurotransmitter release. However, under pathological
      situations, increased PLA2 activity may result in the loss of essential membrane
      glycerophospholipids, resulting in altered membrane permeability, ion
      homeostasis, increased free fatty acid release, and the accumulation of lipid
      peroxides. These processes, along with loss of ATP, may be responsible for the
      loss of membrane phospholipid and subsequent neuronal injury found in ischemia,
      spinal cord injury, and other neurodegenerative diseases. This review outlines
      the current knowledge of the PLA2 found in the central nervous system and
      attempts to define the role of PLA2 during both physiologic and pathologic
      conditions.

PMID- 9282911
TI  - Thyroid hormone-regulated expression of RC3/neurogranin in the immortalized
      hypothalamic cell line GT1-7.
AB  - The calmodulin-binding, protein kinase C substrate RC3/neurogranin is the product
      of a neuron-specific gene expressed in the forebrain that is under specific
      regional and temporal control by thyroid hormone (3,5,3'-triiodothyronine, T3).
      In vivo, some neuronal populations are sensitive and others are insensitive to
      T3. The goal of this study was to identify neuronal cell cultures that express
      RC3/neurogranin, to check whether they are sensitive to T3, and to examine the
      mechanism of regulation. We found that RC3 is induced by T3 in the hypothalamic
      cell line GT1-7 at the transcriptional level. The half-life of the mature mRNA
      was 20 h and was not affected by the hormone. Addition of T3 to the cell culture
      induces neurogranin mRNA after 6 h in the absence of new protein synthesis. These
      results suggest a direct transcriptional effect of T3 mediated through nuclear
      receptors. Indeed, GT1-7 cells express functional T3 receptors, as shown by
      northern blotting, nuclear T3-binding assays, and transactivation of reporter
      genes. The role of retinoic acid and glucocorticoids on RC3 expression was also
      evaluated, because we have previously noted the presence of consensus response
      elements for these hormones in the RC3 upstream promoter region. In contrast to
      T3, neither retinoic acid nor dexamethasone influences neurogranin expression
      despite the presence of respective functional receptors.

PMID- 9282912
TI  - Structural analysis of the proximal region of the microtubule-associated protein
      1B promoter.
AB  - Microtubule-associated protein 1B (MAP1B) is a major cytoskeletal protein
      expressed early during development of the nervous system. Previous analysis of
      the MAP1B gene has identified two alternative promoters that can independently
      regulate neuron-specific expression of MAP1B. To further characterize the MAP1B
      promoters, we performed DNase I hypersensitivity assays in vivo over a range of
      8.5 kb surrounding the transcription initiation sites. These studies identified a
      DNase I-hypersensitive site that was present in brain but not liver nuclei at the
      proximal region of the MAP1B promoter, located between the two transcription
      initiation sites. Fine mapping by S1 nuclease sensitivity localized two adjacent
      sites in the proximal promoter region that contained three symmetrical inverted
      repeats. Electrophoresis mobility shift assays showed that proteins present in
      nuclear extracts can bind two consensus regulatory elements present within the
      proximal promoter region, Sp1 and cyclic AMP response element. In addition, there
      was a specific nuclear protein binding activity with two common sequences, a
      "neuronal motif " and a TCC repeat motif. This binding activity was much more
      abundant in liver than in brain nuclear extracts, suggesting that it may
      represent a negative control element in the tissue-specific expression of the
      MAP1B gene.

PMID- 9282913
TI  - Association of brain protein phosphatase 1 with cytoskeletal targeting/regulatory
      subunits.
AB  - Protein phosphatase 1 catalytic subunit (PP1C) is highly enriched in isolated rat
      postsynaptic densities. Gel overlay analyses using digoxigenin (DIG)-labeled PP1C
      revealed four major rat brain PP1C-binding proteins (PP1bps) with molecular
      masses of approximately 216, 175, 134, and 75 kDa, which were (1) more abundant
      in brain than other rat tissues; (2) differentially expressed in microdissected
      brain regions; and (3) enriched in isolated cortex postsynaptic densities.
      PP1bp175, PP1bp134, PP1bp75, and PP1C were partially released from forebrain
      particulate extracts by incubation at low ionic strength, which destabilizes the
      actin cytoskeleton. Size-exclusion chromatography of solubilized extracts
      separated two main PP1 activities (approximately 600 and approximately 100 kDa).
      PP1bps and PP1C gamma1 were enriched in the approximately 600-kDa peak, but PP1C
      beta was enriched in the approximately 100-kDa peak. Furthermore, PP1bp175 and
      PP1bp134 exhibited lower binding of recombinant DIG-PP1C beta than recombinant
      DIG-PP1C gamma1 or DIG-PP1C alpha. Solubilized PP1bp175 and PP1bp134 interact
      with PP1C under native conditions, because they both (1) coeluted from size
      exclusion and ion-exchange columns; (2) bound to microcystin-LR-Sepharose; and
      (3) coprecipitated using PP1C antibodies. Trypsinolysis of the approximately 600
      kDa form of PP1 increased phosphorylase a phosphatase activity approximately
      fourfold, suggesting that interaction of PP1C with these PP1bps modulates its
      activity. Thus, brain PP1 activity is likely targeted to the cytoskeleton,
      including postsynaptic densities, by isoform-selective binding of PP1C to these
      targeting/regulatory subunits, contributing to the specificity of its
      physiological roles.

PMID- 9282914
TI  - Evidence for nicotinic receptors potentially modulating nociceptive transmission
      at the level of the primary sensory neuron: studies with F11 cells.
AB  - F11 cells are a dorsal root ganglion (DRG) cell line used to model the function
      of authentic type C, peptidergic, nociceptive neurons. The cellular events
      underlying the antinociceptive effects of (+/-)-epibatidine, a nicotinic
      acetylcholine receptor (nAChR) ligand that is 200-fold more potent than morphine,
      is unknown. The present study investigated the ability of cholinergic channel
      activators (ChCAs) to effect nAChR-gated ion flux and modulate the release of
      substance P (SP), a neuropeptide identified to play a critical role in
      nociception. The prototypical agonists (-)-nicotine and (-)-cytisine, the
      ganglionic stimulant 1,1-dimethyl-4-phenylpiperazinium, the novel ChCA ABT-418
      [(S)-3-methyl-5-(-1-methyl-2-pyrrolidinyl)isoxazole], and (+/-)-epibatidine
      evoked a concentration-dependent stimulation of rubidium (86Rb+) efflux with EC50
      values of 14.2 +/- 1.6, 63.4 +/- 24, 3.8 +/- 2.0, 29.8 +/- 2.6, and 0.019 +/-
      0.001 microM as well as maximal intrinsic activities of 100, 97, 69, 75, and
      102%, respectively. The noncompetitive nAChR antagonist mecamylamine potently
      antagonized (-)-nicotine-evoked ion flux, whereas the competitive antagonist
      dihydro-beta-erythroidine was a weak antagonist, giving support to an alpha3beta4
      nAChR subtype. In addition, concentrations of (+/-)-epibatidine, similar to those
      necessary to induce maximal 86Rb+ efflux, evoked spontaneous release of SP from
      these cells, which was blocked by mecamylamine. Furthermore, prolonged exposure
      to (+/-)-epibatidine desensitized the functional response of the nAChR in this
      cell line (IC50 = 12 +/- 9 nM). These findings in F11 cells provide a model to
      investigate the role nAChRs play in modulating DRG cell function, and may lead to
      insights into the role these receptors have in modulating nociceptive
      transmission.

PMID- 9282915
TI  - Interferon-beta is a potent promoter of nerve growth factor production by
      astrocytes.
AB  - Recent clinical evidence has suggested that interferon-beta is efficacious in the
      treatment of the demyelinating disease, multiple sclerosis. The mechanism of its
      efficacy remains unclear, and suggested modes of action have focused on immune
      modulation. Nonimmune effects of interferon-beta may also contribute to its
      efficacy. Given that astrocytes produce a range of neurotrophic factors, we
      examined the possibility that interferon-beta could increase the astrocytic
      production of nerve growth factor (NGF), which has been reported to cause
      oligodendrocytes to proliferate and to extend their processes; these phenotypes
      can impact favorably on remyelination. When the recombinant form of mouse
      interferon-beta was added to mouse astrocyte cultures, a dose-dependent increase
      in NGF mRNA was obtained. The 40-fold increase in NGF mRNA elicited by 1,000 U/ml
      interferon-beta was far more potent than that produced by other NGF-elevating
      agents in this study. In concordance, the protein for NGF was elevated by
      interferon-beta. The production of NGF by interferon-beta may be relevant to its
      clinical efficacy in multiple sclerosis. Furthermore, we suggest the potential
      utility of interferon-beta in Alzheimer's disease.

PMID- 9282917
TI  - A kinase insert isoform of rat TrkA supports nerve growth factor-dependent cell
      survival but not neurite outgrowth.
AB  - To investigate potential differences between the family of Trk receptors that
      might have differential consequences on cell signaling, we generated a rat TrkA
      homologue of the 14-amino acid kinase insert isoform of TrkC termed TrkAKi.
      Signal transduction by the TrkAKi receptor has been investigated and compared
      with the homologous signaling defective TrkC(Ki14) receptor. Herein, we
      demonstrate that TrkAKi receptors show a decrease in the absolute amount of
      kinase activity relative to wild-type TrkA, yet retain normal patterns of
      receptor tyrosine phosphorylation, as determined by phosphopeptide mapping
      studies, unlike TrkC(Ki14). nnr5 cell clones expressing TrkAKi receptors show a
      decrease in nerve growth factor (NGF)-mediated SHC tyrosine phosphorylation and a
      loss of high-affinity TrkA-SHC interaction comparable to those expressing
      TrkC(Ki14). Moreover, nnr5 cells expressing TrkAKi receptors fail to demonstrate
      NGF-dependent tyrosine phosphorylation of the signaling molecules phospholipase
      Cgamma-1, MAP kinase/ERK-1, and SNT. TrkAKi receptors internalize NGF comparable
      to wild-type TrkA, but do not stimulate neurite outgrowth. It is interesting
      that, unlike TrkC(Ki14), TrkAKi receptors retain phosphatidylinositol 3-kinase
      activity and nnr5 cells stably expressing TrkAKi receptors retain NGF-dependent
      cell survival under serum-free conditions. Lastly, TrkAKi receptors fail to
      stimulate three immediate-early genes (NGF1A, NGF1B, and c-fos), suggesting that
      these gene products are not required for NGF-dependent cell survival responses.

PMID- 9282918
TI  - Rubidium uptake and accumulation in peripheral myelinated internodal axons and
      Schwann cells.
AB  - To study mechanisms of K+ transport in peripheral nerve, uptake of rubidium
      (Rb+), a K+ tracer, was characterized in rat tibial nerve myelinated axons and
      glia. Isolated nerve segments were perfused with zero-K+ Ringer's solutions
      containing Rb+ (1-20 mM) and x-ray microanalysis was used to measure water
      content and concentrations of Rb, Na, K, and Cl in internodal axoplasm,
      mitochondria, and Schwann cell cytoplasm and myelin. Both axons and Schwann cells
      were capable of removing extracellular Rb+ (Rb+(o)) and exchanging it for
      internal K+. Uptake into axoplasm, Schwann cytoplasm, and myelin was a saturable
      process over the 1-10 mM Rb+(o) concentration range, although corresponding
      axoplasmic uptake rates were higher than respective glial velocities.
      Mitochondrial accumulation was a linear function of axoplasmic Rb+
      concentrations, which suggests involvement of a nonenzymatic process. At 20 mM
      Rb+(o), a differential stimulatory response was observed; i.e., axoplasmic Rb+
      uptake velocities increased more than fivefold relative to the 10 mM rate, and
      glial cytoplasmic uptake rose almost threefold. Finally, Rb+(o) uptake rate into
      axons and glia was completely inhibited by ouabain (2-4 mM) exposure or
      incubation at 4 degrees C. These results suggest that Rb+ uptake into peripheral
      nerve internodal axons and Schwann cells is mediated by Na+,K+-ATPase activity
      and implicate the presence of axonal- and glial-specific Na+ pump isozymes.

PMID- 9282916
TI  - Cholinergic control of nerve growth factor in adult rats: evidence from cortical
      cholinergic deafferentation and chronic drug treatment.
AB  - It is well documented that nerve growth factor (NGF) plays an important role in
      maintaining functions of cholinergic basal forebrain neurons. In the present
      study, we tested the hypothesis that cholinergic activity controls NGF levels in
      cholinoceptive neurons of the cerebral cortex and hippocampus. To address that
      question, we used both cholinergic deafferentation of cerebral cortex and
      hippocampus by cholinergic immunolesion with 192IgG-saporin and chronic
      pharmacological treatment of sham-treated and immunolesioned rats with the
      cholinergic agonist pilocarpine and the cholinergic antagonist scopolamine. We
      observed an increase in NGF protein levels in the cortex and hippocampus after
      cholinergic immunolesions and also after muscarinic receptor blockade by chronic
      intracerebroventricular scopolamine infusion in sham-treated rats after 2 weeks.
      There was no further increase in the accumulation of NGF after scopolamine
      treatment of immunolesioned rats. Chronic infusion of pilocarpine had no effect
      on cortical and hippocampal NGF protein levels in sham-treated rats. In rats with
      cholinergic immunolesions, however, pilocarpine did prevent the lesion-induced
      accumulation of NGF. There was no effect of cholinergic lesion and drug treatment
      on cortical or hippocampal NGF mRNA levels, consistent with the importance of NGF
      retrograde transport as opposed to its de novo synthesis. This study provides
      strong evidence for the hypothesis that there is cholinergic control of cortical
      and hippocampal NGF protein but not mRNA levels in adult rats.

PMID- 9282919
TI  - Beta-amyloid-induced neurotoxicity of a hybrid septal cell line associated with
      increased tau phosphorylation and expression of beta-amyloid precursor protein.
AB  - Recent evidence suggests that beta-amyloid peptide (beta-AP) may induce tau
      protein phosphorylation, resulting in loss of microtubule binding capacity and
      formation of paired helical filaments. The mechanism by which beta-AP increases
      tau phosphorylation, however, is unclear. Using a hybrid septal cell line, SN56,
      we demonstrate that aggregated beta-AP(1-40) treatment caused cell injury.
      Accompanying the cell injury, the levels of phosphorylated tau as well as total
      tau were enhanced as detected immunochemically by AT8, PHF-1, Tau-1, and Tau-5
      antibodies. Alkaline phosphatase treatment abolished AT8 and PHF-1
      immunoreactivity, confirming that the tau phosphorylation sites were at least at
      Ser(199/202) and Ser396. In association with the increase in tau phosphorylation,
      the immunoreactivity of cell-associated and secreted beta-amyloid precursor
      protein (beta-APP) was markedly elevated. Application of antisense
      oligonucleotide to beta-APP reduced expression of beta-APP and immunoreactivity
      of phosphorylated tau. Control peptide beta-AP(1-28) did not produce significant
      effects on tau phosphorylation, although it slightly increased cell-associated
      beta-APP. These results suggest that betaAP(1-40)-induced tau phosphorylation may
      be associated with increased beta-APP expression in degenerated neurons.

PMID- 9282921
TI  - A novel gelsolin isoform expressed by oligodendrocytes in the central nervous
      system.
AB  - Two isoforms of the Ca2+-sensitive, actin-binding protein gelsolin have been
      identified thus far; one is an intracellular protein, cytoplasmic gelsolin, and
      the other is a secretory protein called plasma gelsolin. Gelsolin expression in
      the mammalian CNS appears to be localized mainly to oligodendrocytes where it is
      presumed that the cytoplasmic isoform predominates. Here, we show that
      oligodendrocytes not only contain cytoplasmic gelsolin, but they also express a
      novel gelsolin isoform that we have named gelsolin-3. Cytoplasmic gelsolin,
      plasma gelsolin, and gelsolin-3 arise by alternative splicing from the same gene.
      The N-terminal amino acid sequence unique to gelsolin-3 is shown to be encoded by
      a single exon in a region previously thought to be an intron in the human
      gelsolin gene. In situ hybridization analysis confirmed that gelsolin-3 mRNA is
      localized primarily to oligodendrocytes in rat brain. In other tissues, gelsolin
      3 shows a more restricted pattern of expression than cytoplasmic gelsolin. These
      data support the view that the gelsolin isoforms have differential roles in the
      regulation of the actin cytoskeleton.

PMID- 9282920
TI  - Inhibition of glial cell line-derived neurotrophic factor induced intracellular
      activity by K-252b on dopaminergic neurons.
AB  - The c-ret protooncogene encodes Ret, the functional tyrosine kinase receptor for
      glial cell line-derived neurotrophic factor (GDNF). K-252b, a known protein
      tyrosine kinase inhibitor, has been shown earlier to inhibit the trophic activity
      of brain-derived neurotrophic factor on dopaminergic (DAergic) neurons and nerve
      growth factor on basal forebrain cholinergic neurons while potentiating
      neurotrophin-3 activity on central cholinergic and peripheral sensory neurons and
      PC12 cells. We tested whether K-252b would modulate GDNF-induced differentiation
      in DAergic neuron cultures. Exposure to 1 ng/ml GDNF increased dopamine (DA)
      uptake 80% above control, whereas treatment with 5 microM K-252b decreased the
      efficacy of GDNF by 60%. Concentrations of GDNF of <100 pg/ml were completely
      inhibited, whereas concentrations of >100 pg/ml were moderately active, between
      10 and 20% above control. In addition, K-252b shifted the ED50 from 20 to 200
      pg/ml. GDNF treatment increased soma size and neurite outgrowth in tyrosine
      hydroxylase-immunoreactive neurons. K-252b inhibited differentiation of these
      morphological parameters induced by GDNF. Furthermore, GDNF stimulated Ret
      autophosphorylation at maximal levels, whereas the inhibition of DA uptake and
      morphological differentiation by K-252b correlated with a significantly decreased
      level of Ret autophosphorylation. Therefore, K-252b is able to inhibit
      intracellular activities induced by GDNF on mesencephalic DAergic neurons.

PMID- 9282922
TI  - Neuronal nitric oxide synthase and calmodulin-dependent protein kinase IIalpha
      undergo neurotoxin-induced proteolysis.
AB  - Calpain (calcium-activated neutral protease) has been implicated as playing a
      role of neuronal injury in cerebral ischemia and excitotoxicity. Here we report
      that, in addition to extreme excitotoxic conditions [N-methyl-D-aspartate (NMDA),
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and kainate
      challenges], other neurotoxins such as maitotoxin, A23187, and okadaic acid also
      induce calpain activation, as detected by m-calpain autolytic fragmentation and
      nonerythroid alpha-spectrin breakdown. Under the same conditions, calmodulin
      dependent protein kinase II-alpha (CaMPK-IIalpha) and neuronal nitric oxide
      synthase (nNOS) are both proteolytically cleaved by calpain. Such fragmentation
      can be reduced by calpain inhibitors (acetyl-Leu-Leu-Nle-CHO and PD151746). In
      vitro digestion of protein extract from cortical cultures with purified mu- and m
      calpain produced fragmentation patterns for CaMPK-IIalpha and nNOS similar to
      those produced in situ. Also, several other calpain-sensitive calmodulin-binding
      proteins (plasma membrane calcium pump, microtubule-associated protein 2, and
      calcineurin A) and protein kinase C-alpha are also degraded in neurotoxin-treated
      cultures. Lastly, in a rat pup model of acute excitotoxicity, intrastriatal
      injection of NMDA resulted in breakdown of CaMPK-IIalpha and nNOS. The
      degradation of CaMPK-IIalpha, nNOS, and other endogenous calpain substrates may
      contribute to the neuronal injury associated with various neurotoxins.

PMID- 9282923
TI  - Transient association of the phosphotyrosine phosphatase SHP-2 with TrkA is
      induced by nerve growth factor.
AB  - Nerve growth factor (NGF) treatment of rat PC12 pheochromocytoma cells results in
      an increase in the tyrosine phosphorylation of the NGF receptor, TrkA, leading to
      differentiation to a neuronal phenotype. Dephosphorylation by protein tyrosine
      phosphatases (PTPases) is thought to play an important role in regulating this
      signaling pathway. To identify PTPases that are recruited to the activated TrkA
      receptor, we used an in-gel PTPase assay to examine the presence of PTPases in
      TrkA immunoprecipitates. The Src homology 2 domain containing PTPase SHP-2 was
      found to associate transiently with TrkA following receptor activation, reaching
      a peak after 1 min of NGF treatment and then decreasing rapidly. The association
      of SHP-2 with TrkA was accompanied by the tyrosine phosphorylation of SHP-2 and
      an association of SHP-2 with multiple tyrosine-phosphorylated proteins. In
      addition, the PTPase activity in SHP-2 immunoprecipitates increased greater than
      twofold after 1 min of NGF treatment. This is the first demonstration that the
      association of SHP-2 with TrkA is induced by NGF and that this association leads
      to SHP-2 activation and tyrosine phosphorylation. We conclude that SHP-2 plays a
      significant role in early biochemical events in TrkA-mediated signal
      transduction.

PMID- 9282924
TI  - Ceramide selectively decreases tau levels in differentiated PC12 cells through
      modulation of calpain I.
AB  - Ceramide has been recently proposed to be a signal mediator in several important
      physiological processes including apoptosis, cellular growth, and
      differentiation. Because the microtubule-associated protein tau plays an
      important role in the establishment and maintenance of neuronal morphology, the
      effects of ceramide on tau were examined. Treatment of differentiated PC12 cells
      with the cell-permeable ceramide derivative N-acetylsphingosine (C2) resulted in
      a significant reduction in tau levels. Significant decreases in tau levels were
      also observed when the cells were treated with another ceramide derivative, N
      hexanoylsphingosine (C6). In addition, C2 treatment increased the levels of a
      calpain-derived spectrin breakdown product but did not alter the levels of two
      cytoskeletal proteins, alpha-actin and alpha-tubulin. Because both tau and
      spectrin are proteolyzed in vitro by the calcium-activated cysteine protease
      calpain, the effects of ceramide analogues on the activity of this protease were
      examined. Treatment of PC12 cells with C2 enhanced calcium-stimulated proteolytic
      activity significantly, as revealed by monitoring the hydrolysis of the membrane
      permeable calpain-selective fluorescence probe N-succinyl-L-leucyl-L-leucyl-L
      valyl-L-tyrosine-7-amido-4-methylcoumarin . This activity increase was not due to
      a direct effect of C2 on calpains, because C2 did not alter the activities of
      purified calpain I or II. In addition, C2 treatment of PC12 cells resulted in a
      significant increase in the levels of calpain I and, to a lesser extent, the
      levels of calpastatin (an endogenous calpain inhibitor protein), whereas the
      levels of calpain II were not changed. Moreover, treatment of the cells with the
      synthetic calpain-specific inhibitor N-carbobenzoxy-L-leucyl-L-leucyl-L-tyrosine
      diazomethyl ketone blocked the C2-induced decreases in tau levels. These results
      indicate that tau levels are regulated in response to a physiological factor and,
      thus, have implications for ceramide-mediated changes in normal and pathological
      neuronal processes.

PMID- 9282925
TI  - Mianserin-induced down-regulation of human 5-hydroxytryptamine2A and 5
      hydroxytryptamine2C receptors stably expressed in the human neuroblastoma cell
      line SH-SY5Y.
AB  - We have assessed the ability of the serotonergic antagonist mianserin to modulate
      the number and functional activity of human 5-hydroxytryptamine2A (5-HT2A) and 5
      HT2C receptors stably expressed in the human neuroblastoma cell line SH-SY5Y.
      Incubation of cells expressing the 5-HT2A receptor with mianserin (100 nM) for 24
      h caused a significant decrease (48%) in the binding capacity of [3H] ketanserin.
      This receptor down-regulation was associated with a corresponding decrease in the
      maximal production of inositol phosphates induced by 5-HT but not by carbachol.
      Exposure of cells expressing the 5-HT2C receptor to mianserin (100 nM) for 72 h
      but not for 24 h similarly resulted in a significant reduction (44%) in
      [3H]mesulergine binding. Corresponding analysis of inositol phosphate production
      by 5-HT at the 5-HT2C receptor after incubation with mianserin showed no change
      in maximal response after 24 h. No change in the binding capacity of either
      radioligand was seen after incubation with mianserin for 1 h. A decrease in the
      binding affinity of both radioligands was also observed after mianserin
      treatment, but this decrease was similar after 1 h of incubation to that seen
      after 24 or 72 h, and was probably due to the retention of mianserin within the
      tissue. We conclude that antagonist down-regulation is evident at human 5-HT2A
      and 5-HT2C receptors stably expressed in a human neuroblastoma cell line and is
      probably mediated by a direct action of mianserin at the receptor.

PMID- 9282926
TI  - Increased expression of calbindin D28k via herpes simplex virus amplicon vector
      decreases calcium ion mobilization and enhances neuronal survival after
      hypoglycemic challenge.
AB  - Disruption of Ca2+ homeostasis often leads to neuron death. Recently, the
      function of calcium-binding proteins as neuronal Ca2+ buffers has been debated.
      We tested whether calbindin D28k functions as an intracellular Ca2+ buffer by
      constructing bicistronic herpes simplex virus vectors to deliver rat calbindin
      cDNA to hippocampal neurons in vitro. Neurons were infected with vectors
      delivering calbindin or a negative control or were mock-infected. After 12 or 24
      h of hypoglycemia, infected cells were made aglycemic during fura-2 calcium
      ratiometric imaging. In response to this challenge, neuronal overexpressing
      calbindin had less Ca2+ mobilized as compared with negative controls or mock
      infected cells. Cells were assayed for survival after 12- or 24-h hypoglycemia or
      aglycemia. The calbindin vector decreased neuronal death due to hypoglycemia but
      not aglycemia. Here we demonstrate, in response to hypoglycemic challenge, both
      decreased Ca2+ mobilization and increased survival of cells infected with the
      calbindin vector.

PMID- 9282928
TI  - Transient ischemia differentially increases tyrosine phosphorylation of NMDA
      receptor subunits 2A and 2B.
AB  - Activation of the N-methyl-D-aspartate (NMDA) receptor has been implicated in the
      events leading to ischemia-induced neuronal cell death. Recent studies have
      indicated that the properties of the NMDA receptor channel may be regulated by
      tyrosine phosphorylation. We have therefore examined the effects of transient
      cerebral ischemia on the tyrosine phosphorylation of NMDA receptor subunits NR2A
      and NR2B in different regions of the rat brain. Transient (15 min) global
      ischemia was produced by the four-vessel occlusion procedure. The tyrosine
      phosphorylation of NR2A and NR2B subunits was examined by immunoprecipitation
      with anti-tyrosine phosphate antibodies followed by immunoblotting with
      antibodies specific for NR2A or NR2B, and by immunoprecipitation with subunit
      specific antibodies followed by immunoblotting with anti-phosphotyrosine
      antibodies. Transient ischemia followed by reperfusion induced large (23-29-fold
      relative to sham-operated controls), rapid (within 15 min of reperfusion), and
      sustained (for at least 24 h) increases in the tyrosine phosphorylation of NR2A
      and smaller increases in that of NR2B in the hippocampus. Ischemia-induced
      tyrosine phosphorylation of NR2 subunits in the hippocampus was higher than that
      of cortical and striatal NR2 subunits. The enhanced tyrosine phosphorylation of
      NR2A or NR2B may contribute to alterations in NMDA receptor function or in
      signaling pathways in the postischemic brain and may be related to pathogenic
      events leading to neuronal death.

PMID- 9282927
TI  - Stimulation of the sympathetic perimesenteric arterial nerves releases
      neuropeptide Y potentiating the vasomotor activity of noradrenaline: involvement
      of neuropeptide Y-Y1 receptors.
AB  - Neuropeptide Y (NPY) appears to be involved in the sympathetic regulation of
      vascular tone. To assess the putative role of NPY in mesenteric circulation, the
      release and biological effect of NPY were examined after electrical stimulation
      of perimesenteric arterial nerves. Nerve stimulation with trains of 2-30 Hz
      increased the perfusion pressure of the arterially perfused rat mesenteric bed in
      a frequency- and time-dependent fashion. Trains of 15-30 Hz significantly
      displaced to the left, approximately threefold, the noradrenaline (NA)-induced
      pressor concentration-response curve, in addition to increasing significantly its
      efficacy. Perfusion with 10 nM exogenous NPY mimicked the electrical stimulation
      effect, causing a threefold leftward shift of the NA concentration-response curve
      and increasing the maximal NA response. These effects were antagonized by 100 nM
      BIBP 3226, indicating the activity of NPY-Y1 receptors. Electrical stimulation of
      the perimesenteric nerves released immunoreactive NPY (ir-NPY) in a frequency
      dependent fashion; the ir-NPY coelutes with synthetic NPY as confirmed by HPLC.
      Both the electrically induced pressor response and the calcium-dependent release
      of NPY were obliterated in preparations perfused with 1 microM guanethidine or in
      rats pretreated intravenously for 48 h with 6-hydroxydopamine, thus revealing the
      sympathetic origin of these phenomena. Only a small proportion of the total NPY
      content in the perimesenteric arterial nerves is released after electrical
      stimulation. Chromatographic studies of the physiological sources of the ir-NPY
      support that NPY fragments are generated via peptidase degradation. The present
      findings demonstrate that NPY is released from the perimesenteric arterial
      sympathetic nerves and acts, via the activation of NPY-Y1 receptors, as the
      mediator responsible for the potentiation of NA's effect on perfusion pressure in
      the isolated rat mesenteric bed.

PMID- 9282929
TI  - M3 muscarinic receptor-mediated enhancement of NMDA-evoked adenosine release in
      rat cortical slices in vitro.
AB  - Acetylcholine plays an important role in cortical arousal. Adenosine is released
      during increased metabolism and has been suggested to be a sleep-promoting
      factor. To understand the interaction of acetylcholine and adenosine in
      regulating cortical excitability, we examined the effect of carbachol on NMDA
      evoked adenosine release and identified the muscarinic receptor subtype that
      mediated this effect in adult rat cortical slices in vitro. Carbachol (to 300
      microM) alone did not affect the basal release of adenosine. However, carbachol
      (100 microM) induced a 253% increase in NMDA (20 microM)-evoked adenosine release
      in the presence of Mg2+. In the absence of Mg2+, carbachol's potentiating effect
      was less (60% increase). The nonselective muscarinic antagonist atropine (1.5
      microM) blocked the facilitatory effect of carbachol on NMDA-evoked adenosine
      release, and this was mimicked by the M3-selective antagonist 4-diphenylacetoxy-N
      methylpiperidine (1 microM). Neither an M1-selective dose of pirenzepine (50 nM)
      nor the M2-selective antagonist methoctramine (1 microM) affected carbachol's
      action on NMDA-evoked adenosine release. Carbachol had no effect on adenosine
      release evoked by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA).
      These results suggest that acetylcholine does not affect basal adenosine release
      but enhances NMDA receptor-mediated evoked adenosine release by acting at M3
      receptors in the cortex. This interaction may have a role in regulating cortical
      neuronal excitability on a long-term basis.

PMID- 9282931
TI  - Catecholamine secretion from bovine adrenal chromaffin cells: the role of the
      Na+/Ca2+ exchanger and the intracellular Ca2+ pool.
AB  - The role of the Na+/Ca2+ exchanger and intracellular nonmitochondrial Ca2+ pool
      in the regulation of cytosolic free calcium concentration ([Ca2+]i) during
      catecholamine secretion was investigated. Catecholamine secretion and [Ca2+]i
      were simultaneously monitored in a single chromaffin cell. After high-K+
      stimulation, control cells and cells in which the Na+/Ca2+ exchange activity was
      inhibited showed similar rates of [Ca2+]i elevation. However, the recovery of
      [Ca2+]i to resting levels was slower in the inhibited cells. Inhibition of the
      exchanger increased the total catecholamine secretion by prolonging the
      secretion. Inhibition of the Ca2+ pump of the intracellular Ca2+ pool with
      thapsigargin caused a significant delay in the recovery of [Ca2+]i and greatly
      enhanced the secretory events. These data suggest that both the Na+/Ca2+
      exchanger and the thapsigargin-sensitive Ca2+ pool are important in the
      regulation of [Ca2+]i and, by modulating the time course of secretion, are
      important in determining the extent of secretion.

PMID- 9282932
TI  - A multisubstrate kinetic mechanism of dopamine transport in the nucleus accumbens
      and its inhibition by cocaine.
AB  - Kinetic studies of dopamine transport into suspensions of nucleus accumbens
      (NAcc) and effects of Na+ and Cl- as cosubstrates were performed using rotating
      disk electrode voltammetry. To mimic chemical neurotransmission, dopamine was
      added as a rapid pulse, and transporter-mediated clearance of dopamine was
      evaluated kinetically. This paradigm was shown to approximate a zero trans entry
      transport experiment. Dopamine was taken up with apparent Km and Vmax values of
      1.3 microM and 375 pmol/s/g wet weight, respectively. Transport exhibited
      apparent trans acceleration. Substitution of Na+ with choline or Cl- with
      isethionate reduced dopamine transport with reaction orders of two and unity,
      respectively, accompanied by reductions in Vmax with no changes in Km. Apparent
      K(Na) and K(Cl) values were 70.0 and 92.1 mM, respectively. Dopamine transport in
      NAcc was found to follow a partially random, sequential mechanism in which
      dopamine and Na+ bind randomly to the transporter followed by binding of Cl-
      before transport. Cocaine inhibited dopamine transport and the influences of the
      other substrates allosterically with an overall Ki of 0.30 microM. Thus, the
      general kinetic mechanism of the transport of dopamine in the NAcc is identical
      to that previously reported by this laboratory for dopamine transport in the
      striatum. However, the dopamine transporter in the NAcc is more tightly regulated
      by Na+, possesses a higher kinetic turnover rate, is four times more sensitive to
      cocaine than the striatal transporter, and exhibits cocaine inhibition
      independent of [substrate]. These findings suggest that cocaine modulates
      chemical signaling in NAcc differently than in striatum, providing down
      regulation of function irrespective of [substrate], thereby enhancing
      dopaminergic signaling more robustly in the NAcc than in the striatum.

PMID- 9282930
TI  - Lysophosphatidic acid-induced proliferation-related signals in astrocytes.
AB  - Lysophosphatidic acid (LPA) is a potent lipid biomediator that is likely to have
      diverse roles in the brain. Thus, LPA-induced events in astrocytes were defined.
      As little as 1 nM LPA induced a rapid increase in the concentration of
      intracellular free calcium ([Ca2+]i) in astrocytes from neonatal rat brains. This
      increase was followed by a slow return to the basal level. Intracellular calcium
      stores were important for the initial rise in [Ca2+]i, whereas the influx of
      extracellular calcium contributed significantly to the extended elevation of
      [Ca2+]i. LPA treatment also resulted in increases in lipid peroxidation and DNA
      synthesis. These increases in [Ca2+]i, lipid peroxidation, and DNA synthesis were
      inhibited by pretreatment of cells with pertussis toxin or H7, a serine/threonine
      protein kinase inhibitor. Moreover, the LPA-induced increase in [Ca2+]i was
      inhibited by a protein kinase C inhibitor, Ro 31-8220, and a calcium-dependent
      protein kinase C inhibitor, Go 6976. The increase in [Ca2+]i was important for
      the LPA-induced increase in lipid peroxidation, whereas the antioxidant, propyl
      gallate, inhibited the LPA-stimulated increases in lipid peroxidation and DNA
      synthesis. In contrast, pertussis toxin, H7, and propyl gallate had no effect on
      LPA-induced inhibition of glutamate uptake. Thus, LPA appears to signal via at
      least two distinctive mechanisms in astrocytes. One is a novel pathway, namely,
      activation of a pertussis toxin-sensitive G protein and participation of a
      protein kinase, leading to sequential increases in [Ca2+]i, lipid peroxidation,
      and DNA synthesis.

PMID- 9282933
TI  - Cations affect [3H]mazindol and [3H]WIN 35,428 binding to the human dopamine
      transporter in a similar fashion.
AB  - The present study addresses the possibility that there are different cocaine
      related and mazindol-related binding domains on the dopamine transporter (DAT)
      that show differential sensitivity to cations. The effects of Zn2+, Mg2+, Hg2+,
      Li+, K+, and Na+ were assessed on the binding of [3H]mazindol and [3H]WIN 35,428
      to the human (h) DAT expressed in C6 glioma cells under identical conditions for
      intact cell and membrane assays. The latter were performed at both 0 and 21
      degrees C. Zn2+ (30-100 microM) stimulated binding of both radioligands to
      membranes, with a relatively smaller effect for [3H]mazindol; Mg2+ (0.1-100
      microM) had no effect; Hg2+ at approximately 3 microM stimulated binding to
      membranes, with a relatively smaller effect for [3H]mazindol than [3H]WIN 35,428
      at 0 degrees C, and at 30-100 microM inhibited both intact cell and membrane
      binding; Li+ and K+ substitution (30-100 mM) inhibited binding to membranes more
      severely than to intact cells; and Na+ substitution was strongly stimulatory.
      With only a few exceptions, the patterns of ion effects were remarkably similar
      for both radioligands at both 0 and 21 degrees C, suggesting the involvement of
      common binding domains on the hDAT impacted similarly by cations. Therefore, if
      there are different binding domains for WIN 35,428 and mazindol, these are not
      affected differentially by the cations studied in the present experiments, except
      for the stimulatory effect of Zn2+ at 0 and 21 degrees C and Hg2+ at 0 degrees C.

PMID- 9282934
TI  - Roles for protein kinase C and mitogen-activated protein kinase in nicotine
      induced secretion from bovine adrenal chromaffin cells.
AB  - Both the Ca2+/phospholipid-dependent protein kinases (protein kinases C, PKCs)
      and mitogen-activated protein kinases (MAPKs) have been implicated as
      participants in the secretory response of bovine adrenomedullary chromaffin
      cells. To investigate a possible role for these kinases in exocytosis and the
      relationship of these kinases to one another, intact chromaffin cells were
      treated with agents that inhibited each of the kinases and analyzed for
      catecholamine release and MAPK/extracellular signal-regulated kinase (ERK) kinase
      (MEK)/MAPK activation after stimulation with secretagogues of differential
      efficacy. Of the three secretagogues tested, inactivation of PKCs by long-term
      phorbol 12-myristate 13-acetate (PMA) treatment or incubation with GF109203X had
      the greatest inhibitory effect on nicotine-induced catecholamine release and
      MEK/MAPK activation, a moderate effect on KCl-induced events, and little, if any,
      effect on Ca2+ ionophore-elicited exocytosis and MEK/MAPK activation. These
      results indicate that PKC plays a significant role in events induced by the
      optimal secretagogue nicotine and a lesser role in exocytosis elicited by the
      suboptimal secretagogues KCl and Ca2+ ionophore. Treatment of cells with the MEK
      activation inhibitor PD098059 completely inhibited MEK/MAPK activation (IC50 1-5
      microM) and partially inhibited catecholamine release induced by all
      secretagogues. However, PD098059 was more effective at inhibiting exocytosis
      induced by suboptimal secretagogues (IC50 approximately 10 microM) than that
      induced by nicotine (IC50 approximately 30 microM). These results suggest a more
      prominent role for MEK/MAPK in basic secretory events activated by suboptimal
      secretagogues than in those activated by the optimal secretagogue nicotine.
      However, PD098059 also partially blocked secretion potentiated by short-term PMA
      treatment, suggesting that PKC can function in part by signaling through MEK/MAPK
      to enhance secretion. Taken together, these results provide evidence for the
      preferential involvement of MEK/MAPK in basic secretory events activated by the
      suboptimal secretagogues KCl and Ca2+ ionophore and the participation of both PKC
      and MEK/MAPK in optimal, secretion induced by nicotine.

PMID- 9282935
TI  - Influence of cannabinoids on electrically evoked dopamine release and cyclic AMP
      generation in the rat striatum.
AB  - Using the endogenous cannabinoid receptor agonist anandamide, the synthetic
      agonist CP 55940 [[1alpha,2beta(R)5alpha]-(-)-5-(1,1-dimethylheptyl+  ++)-2-[5
      hydroxy-2-(3-hydroxypropyl)cyclohexyl]phenol], and the specific antagonist SR
      141716 [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1H
      pyrazole-3-carboxamide hydrochloride], second messenger activation of the central
      cannabinoid receptor (CB1) was examined in rat striatal and cortical slices. The
      effects of these cannabinoid ligands on electrically evoked dopamine (DA) release
      from [3H] dopamine-prelabelled striatal slices were also investigated. CP 55940
      (1 microM) and anandamide (10 microM) caused significant reductions in forskolin
      stimulated cyclic AMP accumulation in rat striatal slices, which were reversed in
      the presence of SR 141716 (1 microM). CP 55940 (1 microM) had no effect on either
      KCl- or neurotransmitter-stimulated 3H-inositol phosphate accumulation in rat
      cortical slices. CP 55940 and anandamide caused significant reductions in the
      release of dopamine after electrical stimulation of [3H]dopamine-prelabelied
      striatal slices, which were antagonised by SR 141716. SR 141716 alone had no
      effect on electrically evoked dopamine release from rat striatal slices. These
      data indicate that the CB1 receptors in rat striatum are negatively linked to
      adenylyl cyclase and dopamine release. That the CB1 receptor may influence
      dopamine release in the striatum suggests that cannabinoids play a modulatory
      role in dopaminergic neuronal pathways.

PMID- 9282936
TI  - Activating mutations of the serotonin 5-HT2C receptor.
AB  - Site-directed mutagenesis was performed to create a mutant serotonin 5-HT2C
      receptor that would mimic the active conformation of the native receptor.
      Structural alteration of receptor conformation was achieved by changing amino
      acid no. 312 from serine to phenylalanine (S312F) or lysine (S312K). After
      expression in COS-7 cells, the binding affinity of 5-HT for [3H]mesulergine
      labeled 5-HT2C receptors increased from 203 nM (native) to 76 nM for S312F and
      6.6 nM for S312K mutant receptors. 5-HT potency for stimulation of
      phosphatidylinositol (PI) hydrolysis increased from 70 nM (native) to 28 nM for
      S312F and 2.7 nM for S312K mutant receptors. The mutant receptors were
      constitutively active, stimulating PI hydrolysis in the absence of agonist. S312F
      and S312K mutations resulted in twofold and five-fold increases, respectively, in
      basal levels of PI hydrolysis. Mianserin and mesulergine displayed inverse
      agonist activity by decreasing basal levels of PI hydrolysis stimulated by S312K
      mutant receptors. [3H]5-HT and [3H]mesulergine labeled the same number of S312K
      mutant receptors and 5'-guanylylimidodiphosphate had no effect on [3H]5-HT
      binding. These results indicate that serine --> lysine mutation at amino acid no.
      312 produces an agonist high-affinity state of the 5-HT2C receptor that
      spontaneously couples to G proteins and stimulates PI hydrolysis in the absence
      of agonist.

PMID- 9282938
TI  - Glutamate uptake impairment and neuronal damage in young and aged rats in vivo.
AB  - The extracellular concentration of glutamate increases during hypoxia/ischemia
      probably due to deficient uptake. Glutamate might contribute to neuronal damage
      associated with this disorder and to neurodegeneration during aging. In the
      present study, we have tested the effect of two inhibitors of glutamate
      transport, L-trans-pyrrolidine-2,4-dicarboxylate and dihydrokainate, on the
      extracellular levels of glutamate and on neuronal damage, which was
      quantitatively studied by image analysis of histological brain sections. Drugs
      were administered by microdialysis and glutamate concentration was determined by
      HPLC in the striatum and the hippocampus of 3-month-old and 22-24-month-old rats.
      In both regions studied, the basal concentration of extracellular glutamate was
      higher in aged than in young rats. Pyrrolidine dicarboxylate induced a
      substantial elevation of extracellular glutamate in both regions, and although
      this increase was almost twofold higher in old than in young animals, no neuronal
      damage was observed. In contrast, dihydrokainate had a poor effect on glutamate
      levels, but induced clear neuronal damage in the striatum and the hippocampus in
      both groups of rats. The present results suggest that age appears not to be a
      significant factor in the sensitivity of neurons to the toxic effect of
      extracellular glutamate increase via blockade of its transport system.

PMID- 9282937
TI  - Stimulation of interleukin-6 secretion and gene transcription in primary
      astrocytes by adenosine.
AB  - During cerebral ischemia, the expression of interleukin-6 (IL-6), which has
      neuroprotective properties, increases. To understand the underlying mechanism,
      the regulation of IL-6 expression by neurotransmitters that accumulate during
      cerebral ischemia was investigated. Adenosine stimulated IL-6 secretion in
      primary astrocytes four- to 10-fold. The effect was concentration dependent, the
      EC50 being approximately 8 microM. Although the nonselective analogue 2
      chloroadenosine (2CA) increased IL-6 secretion to a similar extent, the A1
      selective agonist N6-cyclopentyladenosine or the A2a agonist CGS-21680 had only a
      marginal effect on IL-6 secretion. IL-6 secretion stimulated by 2CA (10 microM)
      was inhibited by the nonselective adenosine antagonist 8-(p
      sulfophenyl)theophylline, whereas the A1-selective antagonist 8-cyclopentyl-1,3
      dipropylxanthine or the A2a-selective antagonist 8-(3-chlorostyryl)caffeine had
      no effect, to a concentration of 0.1 microM. Transcription of the IL-6 gene was
      investigated by transfecting primary astrocytes with a reporter fusion gene
      containing the human IL-6 promoter (-179/+12). 2CA stimulated IL-6 gene
      transcription 2.5-fold. Mutations of the binding site for NF-kappaB or NF-IL6
      abrogated the response to 2CA. Thus, an increase of extracellular adenosine
      during focal cerebral ischemia may stimulate IL-6 expression via A2b receptors.
      The induction of IL-6 expression appears to involve a transcriptional effect that
      depends on NF-kappaB and NF-IL6.

PMID- 9282939
TI  - The lipid peroxidation product, 4-hydroxy-2-trans-nonenal, alters the
      conformation of cortical synaptosomal membrane proteins.
AB  - Alzheimer's disease (AD) is widely held to be a disorder associated with
      oxidative stress due, in part, to the membrane action of amyloid beta-peptide (A
      beta). A beta-associated free radicals cause lipid peroxidation, a major product
      of which is 4-hydroxy-2-trans-nonenal (HNE). We determined whether HNE would
      alter the conformation of synaptosomal membrane proteins, which might be related
      to the known neurotoxicity of A beta and HNE. Electron paramagnetic resonance
      spectroscopy, using a protein-specific spin label, MAL-6 (2,2,6,6-tetramethyl-4
      maleimidopiperidin-1-oxyl), was used to probe conformational changes in gerbil
      cortical synaptosomal membrane proteins, and a lipid-specific stearic acid label,
      5-nitroxide stearate, was used to probe for HNE-induced alterations in the
      fluidity of the bilayer domain of these membranes. Synaptosomal membranes,
      incubated with low concentrations of HNE, exhibited changes in protein
      conformation and bilayer order and motion (fluidity). The changes in protein
      conformation were found to be concentration- and time-dependent. Significant
      protein conformational changes were observed at physiologically relevant
      concentrations of 1-10 microM HNE, reminiscent of similar changes in synaptosomal
      membrane proteins from senile plaque- and A beta-rich AD hippocampal and inferior
      parietal brain regions. HNE-induced modifications in the physical state of gerbil
      synaptosomal membrane proteins were prevented completely by using excess
      glutathione ethyl ester, known to protect neurons from HNE-caused neurotoxicity.
      Membrane fluidity was found to increase at higher concentrations of HNE (50
      microM). The results obtained are discussed with relevance to the hypothesis of A
      beta-induced free radical-mediated lipid peroxidation, leading to subsequent HNE
      induced alterations in the structure and function of key membrane proteins with
      consequent neurotoxicity in AD brain.

PMID- 9282940
TI  - Regulation of actin and its mRNA by thyroid hormones in cultures of fetal human
      brain during second trimester of gestation.
AB  - The effect of thyroid hormones (THs) on the expression of actin gene during fetal
      human brain development and the period of sensitivity to the hormones have been
      investigated. Developmental profile of actin in the cytoskeletal (CSK) and
      noncytoskeletal (non-CSK) fractions in the fetal cerebra showed a pronounced rise
      in the level of CSK actin at weeks 17-19. Northern blot analysis also revealed a
      sharp rise in the level of actin mRNA at weeks 16-18, temporally coinciding with
      the period of rise of THs and peak expression of TH receptors in the fetal brain.
      In organ cultures of weeks 13-23 fetal cerebra, THs elicited a general
      stimulation of CSK proteins at all ages studied with a preferential effect on
      actin at weeks 17-19. During this period, THs also stimulated the rate of
      synthesis of actin. Kinetics of induction of actin by TH in the non-CSK and CSK
      fractions in organ cultures of week 17 fetal cerebra showed an increased level of
      actin in both fractions within 1 h. Subsequently (at 5 and 18 h), induction was
      evident only in the insoluble CSK fraction, suggesting an effect of the hormone
      on the intracellular distribution of actin between the soluble non-CSK fraction
      and the insoluble CSK fraction. Correspondingly, in cultures of week 17 fetal
      cerebra, THs elicited an increase in actin mRNA level within 30 min of hormonal
      exposure. The overall results suggest that THs regulate the expression of actin
      gene by stimulating the rate of synthesis as well as intracellular distribution
      of actin during the mid phase of the second trimester of gestation.

PMID- 9282941
TI  - The amyloid beta-protein of Alzheimer's disease increases acetylcholinesterase
      expression by increasing intracellular calcium in embryonal carcinoma P19 cells.
AB  - One of the characteristic changes that occurs in Alzheimer's disease is the loss
      of acetylcholinesterase (AChE) from both cholinergic and noncholinergic neurons
      of the brain. However, AChE activity is increased around amyloid plaques. This
      increase in AChE may be of significance for therapeutic strategies using AChE
      inhibitors. The aim of this study was to examine the effect of amyloid beta
      protein (A beta), the major component of amyloid plaques, on AChE expression. A
      beta peptides spanning residues 1-40 or 25-35 increased AChE activity in P19
      embryonal carcinoma cells. A peptide containing a scrambled A beta(25-35)
      sequence did not stimulate AChE expression. To examine the possibility that the
      increase in AChE expression was mediated by an influx of calcium through voltage
      dependent calcium channels (VDCCs), drugs acting on VDCCs were tested for their
      effects. Inhibitors of L-type VDCCs (diltiazem, nifedipine, and verapamil), but
      not N- or P- or Q-type VDCCs, resulted in a decrease in AChE expression. Agonists
      of L-type VDCCs (maitotoxin and S(-)-Bay K 8644) increased AChE expression. As L
      type VDCCs are known to be modulated by cyclic AMP-dependent protein kinase, the
      effect of the adenylate cyclase activator forskolin was also examined. Forskolin
      stimulated AChE expression, an action that was blocked by the L-type VDCC
      antagonist nifedipine. The A beta(25-35)induced increase in AChE expression was
      mediated by an L-type VDCC, as the effect was also blocked by nifedipine. The
      results suggest that the increase in AChE expression around amyloid plaques could
      be due to a disturbance in calcium homeostasis involving the opening of L-type
      VDCCs.

PMID- 9282942
TI  - Inhibition of glutamate transport in synaptosomes by dopamine oxidation and
      reactive oxygen species.
AB  - Dopamine can form reactive oxygen species and other reactive metabolites that can
      modify proteins and other cellular constituents. In this study, we tested the
      effect of dopamine oxidation products, other generators of reactive oxygen
      species, and a sulfhydryl modifier on the function of glutamate transporter
      proteins. We also compared any effects with those on the dopamine transporter, a
      protein whose function we had previously shown to be inhibited by dopamine
      oxidation. Preincubation with the generators of reactive oxygen species,
      ascorbate (0.85 mM) or xanthine (500 microM) plus xanthine oxidase (25 mU/ml),
      inhibited the uptake of [3H]glutamate (10 microM) into rat striatal synaptosomes
      (-54 and -74%, respectively). The sulfhydryl-modifying agent N-ethylmaleimide (50
      500 microM) also led to a dose-dependent inhibition of [3H]glutamate uptake.
      Preincubation with dopamine (100 microM) under oxidizing conditions inhibited
      [3H]glutamate uptake by 25%. Exposure of synaptosomes to increasing amounts of
      dopamine quinone by enzymatically oxidizing dopamine with tyrosinase (2-50 U/ml)
      further inhibited [3H]glutamate uptake, an effect prevented by the addition of
      glutathione. The effects of free radical generators and dopamine oxidation on
      [3H]glutamate uptake were similar to the effects on [3H]dopamine uptake (250 nM).
      Our findings suggest that reactive oxygen species and dopamine oxidation products
      can modify glutamate transport function, which may have implications for
      neurodegenerative processes such as ischemia, methamphetamine-induced toxicity,
      and Parkinson's disease.

PMID- 9282943
TI  - Oxidative DNA damage in the parkinsonian brain: an apparent selective increase in
      8-hydroxyguanine levels in substantia nigra.
AB  - Oxidative damage has been implicated in the pathology of Parkinson's disease
      (PD), e.g., rises in the level of the DNA damage product, 8-hydroxy-2'
      deoxyguanosine, have been reported. However, many other products result from
      oxidative DNA damage, and the pattern of products can be diagnostic of the
      oxidizing species. Gas chromatography/mass spectrometry was used to examine
      products of oxidation and deamination of all four DNA bases in control and PD
      brains. Products were detected in all brain regions examined, both normal and PD.
      Analysis showed that levels of 8-hydroxyguanine (8-OHG) tended to be elevated and
      levels of 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FAPy guanine) tended to be
      decreased in PD. The most striking difference was a rise in 8-OHG in PD
      substantia nigra (p = 0.0002); rises in other base oxidation/deamination products
      were not evident, showing that elevation in 8-OHG is unlikely to be due to
      peroxynitrite (ONOO-) or hydroxyl radicals (OH.), or to be a prooxidant effect of
      treatment with L-Dopa. However, some or all of the rise in 8-OHG could be due to
      a change in 8-OHG/FAPy guanine ratios rather than to an increase in total
      oxidative guanine damage.

PMID- 9282944
TI  - Selective aggregation of endogenous beta-amyloid peptide and soluble amyloid
      precursor protein in cerebrospinal fluid by zinc.
AB  - Zinc added to buffered solutions of synthetic beta-amyloid peptide (A beta) has
      been reported to induce accelerated formation of insoluble aggregates. This
      observation suggests that zinc may play a role in the formation of senile
      plaques, which contain A beta, in Alzheimer's disease. To test this hypothesis
      under conditions more representative of the brain, we investigated the ability of
      zinc to induce aggregation of A beta in freshly drawn canine CSF, which contains
      the same sequence as human A beta. Aggregates were separated from CSF by
      ultracentrifugation before and after incubation with zinc and assayed by
      quantitative western blotting and ELISA. We found that zinc induced the rapid
      aggregation of endogenous A beta in CSF, with an EC50 of 120-140 microM. The
      reaction was specific, because most (> or = 95%) CSF protein remained soluble
      under conditions where most A beta was insoluble, as assayed by scanning
      densitometry of Coomassie-stained gels. Staining of the precipitated material
      resulted in the visualization of punctate regions that were thioflavin positive
      or birefringent when stained with Congo red, suggesting the formation of amyloid
      related structures. These results suggest that zinc could play a role in amyloid
      deposition, because there is overlap between the regions of the brain where zinc
      concentrations are highest and regions with the highest amyloid content. It is
      surprising that zinc induced the aggregation of endogenous soluble APP at lower
      concentrations than required for A beta (EC50 80 microM). The possibility that
      zinc-induced aggregation of APP may precede the deposition of A beta into plaques
      is discussed. Investigation of aggregation of A beta in CSF will aid in assessing
      the biological relevance of other agents that have been reported to accelerate
      amyloid formation.

PMID- 9282945
TI  - Expression of pituitary adenylate cyclase-activating polypeptide (PACAP)
      receptors and PACAP in human fetal retina.
AB  - Specific receptors for pituitary adenylate cyclase-activating polypeptide
      (PACAP), a novel peptide with neuroregulatory and neurotrophic functions, have
      recently been identified in the retinas of different mammalian species. In the
      present study, expression of PACAP receptors and PACAP was investigated in the
      retinas of 12-18-week human embryos. Radioligand binding studies showed that the
      two forms of PACAP with 38 and 27 amino acids (PACAP 38 and PACAP 27,
      respectively) displaced the binding of 125I-PACAP 27 with IC50 values in the
      picomolar range, whereas functional receptor assays demonstrated that the two
      peptides were potent and effective stimulators of adenylyl cyclase activity. In
      contrast, vasoactive intestinal peptide (VIP) and human peptide histidine
      isoleucine, which are homologous to PACAP, displayed lower affinities for the
      125I-PACAP 27 binding site and were much less potent stimulators of cyclic AMP
      formation. Glucagon and secretin were inactive in both receptor assays. The
      expression of specific PACAP receptors was further investigated by reverse
      transcription-polymerase chain reaction technique, which showed the presence of
      mRNAs coding for PACAP type I and for nonselective PACAP type II (both VIP1 and
      VIP2) receptors. By the same technique, expression of PACAP mRNA was also
      detected. These data indicate that the developing human retina synthesizes PACAP
      and that the peptide may act on retinal cells by predominantly stimulating PACAP
      type I receptors coupled to cyclic AMP formation.

PMID- 9282946
TI  - Hyperglycemic damage to mitochondrial membranes during cerebral ischemia:
      amelioration by platelet-activating factor antagonist BN 50739.
AB  - The Pulsinelli-Brierley four-vessel occlusion model was used to study the
      consequences of hyperglycemic ischemia and reperfusion. Rats were subjected to
      either 30 min of normo- or hyperglycemic ischemia or 30 min of normo- or
      hyperglycemic ischemia followed by 60 min of reperfusion. In some animals, 2
      mg/kg BN 50739, a platelet-activating factor receptor antagonist, was
      administered intraarterially either before or after the ischemic insult. The
      changes in mitochondrial membrane free fatty acid levels, phosphatidylcholine
      fatty acyl composition, and thiobarbituric acid-reactive material (TBAR) content
      plus the mitochondrial respiratory control ratio (RCR) were monitored. When the
      platelet-activating factor antagonist was present during normoglycemia, (a) the
      mitochondrial free fatty acid release both during and after ischemia was slowed,
      (b) reacylation of phosphatidylcholine following ischemia was promoted, and (c)
      TBAR accumulation during and following ischemia was decreased. The detrimental
      effects of hyperglycemia were muted when BN 50739 was present during ischemia.
      The RCR was preserved and phosphatidylcholine hydrolysis during ischemia was
      decreased. TBAR levels were consistently higher in hyperglycemic brain
      mitochondria both during and after ischemia. The RCR correlated directly with
      mitochondrial phosphatidylcholine polyunsaturated fatty acid content during
      ischemia and reperfusion. BN 50739 protection of mitochondrial membranes in brain
      may be influenced by tissue pH.

PMID- 9282947
TI  - Adenosine triphosphate degradation products after oxidative stress and metabolic
      dysfunction in cultured retinal cells.
AB  - The alteration in energy metabolic products was analyzed in cultured retinal
      cells submitted to oxidative stress, hypoxia, glucopenia, or ischemia-like
      conditions. Ischemia highly reduced cellular ATP and increased AMP formation,
      without significant changes in ADP. Ischemia induced a significant increase in
      extracellular adenosine (ADO) and hypoxanthine (HYP), and to a lesser extent
      inosine (INO). Glucopenia reduced cellular ATP by about two- to threefold, which
      was not compensated for by AMP formation. Under glucopenia, extracellular ADO and
      HYP were significantly increased, although a major increase in extracellular INO
      was observed. 5-(4-Nitrobenzyl)-6-thioinosine (10 microM) reduced extracellular
      ADO during glucopenia or ischemia by approximately 80%, indicating that ADO
      accumulation occurs mainly via the transporter. Intracellular ATP, ADP, or AMP
      and extracellular ADO, INO, or HYP were not apparently changed after oxidative
      stress or hypoxia. Nevertheless, in the presence of 10 microM erythro-9-(2
      hydroxy-3-nonyl)adenosine, oxidative stress was shown to increase significantly
      the accumulation of ADO, which was reduced in the presence of 200 microM
      alpha,beta-methyleneadenosine 5'-diphosphate, suggesting that ADO accumulation
      after oxidative stress may result from extracellular degradation of adenine
      nucleotides. The increase in ADO accumulation resulting from the depletion of
      cellular ATP was directly related to the release of endogenous glutamate
      occurring through a Ca2+-independent pathway after ischemia. Increased metabolic
      products derived from ATP are suggested to exert a modulating effect against
      excitotoxic neuronal death.

PMID- 9282948
TI  - Brain and spinal cord distribution of biphalin: correlation with opioid receptor
      density and mechanism of CNS entry.
AB  - Biphalin [(Tyr-D-Ala-Gly-Phe-NH)2] is a bivalent, opioid peptide containing two
      pharmacophores linked by a hydrazine bridge. When administered
      intracerebroventricularly, it has been shown to be more potent than morphine and
      etorphine at eliciting antinociception. Biphalin has also been shown to cross
      both the blood-brain and blood-cerebrospinal fluid barriers. To understand the
      basis of biphalin's potency, regional brain and spinal cord distribution studies
      with [125I-Tyr1]biphalin were performed 5, 20, and 40 min after intravenous bolus
      injections. A statistically greater amount of [125I-Tyr1]biphalin was detected in
      the nucleus accumbens compared with other brain regions (p < 0.05). This
      correlates with the high density of delta- and mu-opioid receptor mRNA and
      binding sites shown to be expressed in the nucleus accumbens. Also, a
      statistically greater amount of [125I-Tyr1] biphalin was detected in two other
      circumventricular organs, the choroid plexus and pituitary, when compared with
      other brain regions. These studies provide evidence that biphalin can reach not
      only brain sites, but also spinal sites to elicit antinociception. The overall
      CNS distribution of [125I-Tyr1]biphalin was decreased with naloxone, D-Phe-Cys
      Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2, or naltrindole pretreatment, showing that biphalin
      detected in the brain and spinal cord is binding to delta- and mu-opioid
      receptors. Additional in situ brain perfusion experiments identified a saturable
      component contributing to CNS entry of [125I-Tyr1]biphalin, which could be
      described by Michaelis-Menten kinetics with a Km of 2.6 +/- 4.8 microM, Vmax of
      14.6 +/- 2.89 pmol(-1) x min(-1) x g(-1), and Kd of 0.568 +/- 0.157 microl x min(
      1) x g(-1). Brain entry of [125I-Tyr1]biphalin was sensitive to 2
      aminobicyclo[2.2.1]heptane-2-carboxylic acid and L-phenylalanine, suggesting use
      of the large neutral amino acid carrier. This work provides evidence that
      biphalin is a promising, potent analgesic that has a unique mechanism for
      reaching both spinal and supraspinal opioid receptor sites.

PMID- 9282950
TI  - Oxidant injury in PC12 cells--a possible model of calcium "dysregulation" in
      aging: I. Selectivity of protection against oxidative stress.
AB  - Previous research has suggested that the initial effects of cellular free radical
      neurotoxic insult involve large increases in intracellular Ca2+. However, the
      exact role of oxidative stress on the various parameters involved in these
      increases has not been specified. The present experiments were performed to
      examine these parameters in PC12 cells exposed to 5, 25, or 300 microM H2O2 for
      30 min in growth medium alone or containing either nifedipine (L-type Ca2+
      antagonist), conotoxin (N-type antagonist), Trolox (vitamin E analogue), or alpha
      phenyl-n-tert-butylnitrone (nitrone trapping agent; PBN). The concentrations of
      H2O2 were chosen by examining the degree of cell killing induced by exposure to
      graded concentrations of H2O2. The 5 and 25 microM concentrations of H2O2
      produced no significant cell killing at either 30 min or 24 h after treatment,
      whereas the 300 microM concentration produced a moderate degree of cell killing
      that did not increase between the two times. Fluorescent imaging was used to
      visualize intracellular Ca2+ changes in fura-2-loaded cells. Baseline (pre-30 mM
      KCl) Ca2+ levels were increased significantly by H2O2 treatment (e.g., 300
      microM, 200%), but the rise in the level of free intracellular Ca2+ after KCl
      stimulation (i.e., peak) was decreased (e.g., 300 microM, 50%) and the cell's
      ability to sequester or extrude the excess Ca2+ (i.e., Ca2+ recovery time) after
      depolarization was decreased significantly. All compounds prevented baseline Ca2+
      increases and, with the exception of conotoxin, antagonized the peak decreases in
      Ca2+. It is interesting that after 300 microM H2O2 exposure, only Trolox was
      partially effective in preventing these deficits in recovery. Conotoxin increased
      the decrement recovery in the absence of H2O2. However, in cells exposed to 5 or
      25 microM H2O2, conotoxin as well as the other agents were effective in
      preventing the deficits in recovery.

PMID- 9282949
TI  - Relations between the extracellular concentrations of choline and acetylcholine
      in rat striatum.
AB  - Changes in extracellular levels of acetylcholine (ACh) and choline (Ch) in the
      striatum of rats were examined by in vivo microdialysis after intraperitoneal
      injections of drugs. A dopamine D2 antagonist, sulpiride (20 mg/kg), and a
      muscarinic antagonist, atropine (3.5 mg/ kg), increased ACh levels and decreased
      Ch levels. On the contrary, the D2 agonist (+/-)-2-(N-phenylethyl-N-propyl)amino
      5-hydroxytetralin (N-434; 5 mg/kg) and an anesthetic, pentobarbital (50 mg/kg),
      decreased ACh levels and increased Ch levels. Perfusion of 10 microM
      hemicholinium-3 (HC-3), a Ch uptake inhibitor, through the striatum induced a
      complete inhibition of ACh release and increased Ch levels in all drug-treated
      groups. The degree of relative increase in the level of Ch induced by HC-3
      differed among the drug-pretreated groups; compared with the control group, the
      relative increase was larger in the sulpiride- and atropine-treated groups and
      smaller in the N-434 and pentobarbital-treated groups. Thus, we demonstrated
      reciprocal relations between extracellular concentrations of Ch and ACh after
      treatments by drugs. The data suggest that in the striatum, which is rich in
      cholinergic innervation, the extracellular Ch concentration is to a large extent
      determined by activity of the cholinergic transmission reflected in high-affinity
      choline uptake.

PMID- 9282951
TI  - Oxidant injury in PC12 cells--a possible model of calcium "dysregulation" in
      aging: II. Interactions with membrane lipids.
AB  - In a model recently developed to study the parameters altering vulnerability to
      oxidative stress, it was shown via image analysis that H2O2-exposed PC12 cells
      exhibited increased levels of intracellular Ca2+ (baseline), decreases in K+
      stimulated Ca2+ levels (peak), and decreased poststimulation Ca2+ clearance
      (recovery). The present experiments were performed to determine if the response
      patterns in these parameters to oxidative stress would be altered after
      modification of membrane lipid composition induced by incubating the PC12 cells
      with 660 microM cholesterol (CHL) in the presence or absence of 500 microM
      sphingomyelin (SPH) before low (5 microM) or high (300 microM) H2O2 exposure.
      Neither CHL nor SPH had synergistic effects with high concentrations of H2O2 on
      baseline. However, CHL in the presence or absence of SPH reversed the effect of
      low concentrations of H2O2 on baseline. SPH decreased significantly the cell's
      ability to clear excess Ca2+ in the presence or absence of H2O2 and increased
      significantly the level of conjugated dienes (CDs). It is surprising that in the
      cells pretreated with CHL, the CD levels were not significantly different from
      controls. However, in the presence of SPH, the effects of CHL on CDs were
      altered. These results suggest that the ratios of membrane lipids could be of
      critical importance in determining the vulnerability to oxidative stress and Ca2+
      translocation in membranes. This may be of critical importance in aging where
      there is increased membrane SPH and significant loss of calcium homeostasis.

PMID- 9282952
TI  - Opposite regulation of adenylyl cyclase by protein kinase C in astrocyte and
      microglia cultures.
AB  - We studied the regulation of cyclic AMP responses by protein kinase C (PKC) in
      purified astrocyte and microglia cultures obtained from the neonatal rat brain.
      In astrocytes, a 10-min treatment with the phorbol esters phorbol 12-myristate 13
      acetate (PMA) and 4beta-phorbol 12,13-didecanoate (4beta-PDD) (but not with
      4alpha-PDD) or with diacylglycerol, which activate PKC, dose-dependently enhanced
      cyclic AMP accumulation induced by the beta-adrenergic agonist isoproterenol and
      the adenylyl cyclase activator forskolin. Such enhancement was prevented by the
      PKC inhibitors staurosporine and calphostin-C and by down-regulation of PKC and
      was not related to activation of membrane receptors or Gs proteins or to
      inhibition of Gi proteins or phosphodiesterases. Instead, the activity of
      adenylyl cyclase doubled in PMA-treated astrocytes. In microglia, a 10-min
      treatment with PMA or PKC inhibitors did not affect cyclic AMP accumulation,
      whereas longer treatments with PMA or 4beta-PDD (but not 4alpha-PDD) inhibited
      the cyclic AMP response in a time- and dose-dependent manner. Such inhibition was
      mimicked by staurosporine and calphostin-C. Also, in the case of microglia, the
      modulation of cyclic AMP responses appeared to occur at the level of adenylyl
      cyclase, and not elsewhere in the cyclic AMP cascade. The inhibition of
      microglial adenylyl cyclase was apparently not due to aspecific cytotoxicity. A
      differential regulation of adenylyl cyclase by PKC in astrocytes and microglia
      may help to explain qualitative and quantitative differences in the response of
      these cells to various physiological and pathological stimuli.

PMID- 9282954
TI  - In vivo evidence for the link between L- and D-serine metabolism in rat cerebral
      cortex.
AB  - To obtain an insight into the metabolic pathways of endogenous D-serine in
      mammalian brains, we have investigated in the infant rat the effects of systemic
      administration of L-serine, D-serine, and related amino acids, including glycine
      and threonine, on the amino acid contents in the cerebral cortex. Intraperitoneal
      injection of L-serine induced a rapid and transient elevation of the levels of L
      serine itself in the neocortex, with its peak at 3 h post injection, and a
      delayed and prolonged increase in D-serine contents from 1.5 h to at least 24 h
      thereafter. Similarly, a significant augmentation in cerebral D-serine contents
      was observed 6 h after intraperitoneal administration of glycine, which also
      elevated the cortical L-serine levels. In contrast, L-threonine injection
      affected the concentrations of neither D- nor L-serine in the cortex of the pups.
      D-Serine given systemically, in turn, increased the neocortical contents of L
      serine as well as D-serine itself, but failed to alter those of glycine and L
      threonine. These in vivo data suggest the possible link between metabolic
      pathways of D- and L-serine in the cerebral cortex of the rat.

PMID- 9282953
TI  - Functional coupling of endogenous serotonin (5-HT1B) and calcitonin (C1a)
      receptors in CHO cells to a cyclic AMP-responsive luciferase reporter gene.
AB  - A cyclic AMP-responsive reporter cell line has been established through the
      stable expression of a luciferase reporter plasmid in Chinese hamster ovary (CHO)
      cells. Reporter cells showed a dose-dependent expression of luciferase in
      response to incubation with forskolin. These CHO cells were screened for
      endogenous G protein-coupled receptors capable of stimulating or inhibiting
      adenylyl cyclase, by monitoring changes in luciferase expression. Serotonin (5
      HT) receptor agonist ligands caused an inhibition of forskolin-stimulated
      luciferase expression in the rank order 5-carboxamidotryptamine > 5-HT >
      sumatriptan > 8-hydroxy-2-(di-n-propylamino)tetralin. The response to 5-HT was
      reversed by the 5-HT1 receptor antagonists cyanopindolol and pindolol, but not
      the 5-HT2 receptor antagonist ketanserin. Calcitonin was more potent than
      calcitonin gene-related peptide (CGRP) at stimulating luciferase expression in
      this cell line, and these responses were insensitive to the CGRP receptor
      antagonist, CGRP (8-37). These results were consistent with the presence of 5
      HT(1B-like) and calcitonin (C1a-like) receptors in CHO cells, with the responses
      to 5-HT and CGRP being pertussis and cholera toxin-sensitive, respectively. This
      reporter gene assay gave the expected pharmacological profile for these receptors
      when compared with cyclic AMP accumulation assays, confirming its value as a
      functional assay for G protein-coupled receptors linked to adenylyl cyclase.

PMID- 9282955
TI  - Studies of inositol phosphate export from neuronal tissue in vitro.
AB  - Recent in vivo microdialysis studies have demonstrated the presence of
      extracellular levels of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] that can be
      increased in a concentration-dependent manner by muscarinic receptor activation.
      The aim of the present study was to determine whether extracellular levels of
      Ins(1,4,5)P3 could be measured in vitro. Despite rapid increases in internal
      Ins(1,4,5)P3 levels after stimulation with 1 mM carbachol, there was no change in
      external levels in both rat brain cortical slices and human neuroblastoma SH-SY5Y
      cells. Suprafusion of myo-[3H]inositol-prelabelled hippocampal slices with 1 mM
      carbachol caused an increase in 3H-inositol phosphates over basal levels in the
      perfusate after 10 min, reaching a peak (223 +/- 56% of basal) 20 min after
      suprafusion with carbachol was started. This response to carbachol was
      potentiated in the presence of 30 mM K+. Analysis of the individual 3H-inositol
      phosphates in the perfusate revealed that levels of [3H]inositol monophosphate,
      [3H]inositol bisphosphate, [3H]inositol trisphosphate, and [3H]inositol
      tetrakisphosphate were all significantly increased. A similar increase in
      extracellular 3H-inositol phosphates was demonstrated in SH-SY5Y cells incubated
      with 1 mM carbachol for 30 min. This response was again enhanced by 30 mM K+,
      although the intracellular response was not potentiated. Possible roles for
      extracellular inositol phosphates are discussed.

PMID- 9282957
TI  - Distinct loci mediate the direct and indirect actions of the anesthetic etomidate
      at GABA(A) receptors.
AB  - Most general anesthetics produce two distinct actions at GABA(A) receptors. Thus,
      these drugs augment GABA-gated chloride currents (referred to as an indirect
      action) and, at higher concentrations, elicit chloride currents in the absence of
      GABA (referred to as a direct action). Because a beta subunit appears to be
      required for the direct action of intravenous anesthetics in recombinant GABA(A)
      receptors, site-directed mutagenesis of the beta3 subunit was performed to
      identify amino acid residues that are critical for this action. In HEK293 cells
      expressing a prototypical GABA(A) receptor composed of alpha1beta3gamma2
      subunits, mutation of amino acid 290 from Asn to Ser dramatically reduced both
      etomidate-induced chloride currents and its ability to stimulate
      [3H]flunitrazepam binding. By contrast, the ability of etomidate to augment GABA
      gated chloride currents and GABA-enhanced [3H]flunitrazepam binding was retained.
      The demonstration that the direct, but not the indirect, actions of etomidate are
      dependent on beta3(Asn290) indicates that the dual actions of this intravenous
      anesthetic at GABA(A) receptors are mediated via distinct loci.

PMID- 9282956
TI  - Activation of phosphodiesterase IV during desensitization of the A2A adenosine
      receptor-mediated cyclic AMP response in rat pheochromocytoma (PC12) cells.
AB  - Prolonged activation of an A2A adenosine receptor significantly inhibits the
      cellular response to subsequent stimulation (A2A desensitization). We have
      reported previously that activation of phosphodiesterase (PDE) contributes to A2A
      desensitization in PC12 cells. In the present study, we show that a type IV PDE
      (PDE4)-selective inhibitor (Ro 20-1724) effectively blocks the increase in PDE
      activity in desensitized cells. Thus, PDE4 appears to be the PDE specifically
      activated during A2A desensitization in PC12 cells. Prolonged treatment of PC12
      cells with an A2A-selective agonist (CGS21680) leads to increased PDE4 activity
      in a dose-dependent manner, which can be blocked by an A2A-selective antagonist
      [8-(3-chlorostyryl)caffeine]. Using two PDE4 antibodies, we were able to
      demonstrate that the levels of two PDE4-immunoreactive bands (72 and 79 kDa) were
      increased significantly during A2A desensitization. Prolonged treatment with
      forskolin to elevate intracellular cyclic AMP contents also resulted in increased
      PDE4 activity. In addition, activation of PDE4 activity during A2A
      desensitization could be blocked by a protein kinase A (PKA)-selective inhibitor
      (H89) and was not observed in a PKA-deficient PC12 cell line (A123). Taken
      together, activation of PDE4 via a cyclic AMP/PKA-dependent pathway plays a
      critical role in dampening the signal of the A2A receptor.

PMID- 9282958
TI  - Mast cells contain large quantities of secretagogue-sensitive N-acetylaspartate.
AB  - Mast cells play a central role in both immediate allergic reactions and
      inflammation. A functional nerve-mast cell interaction has been proposed, given
      the morphological association between mast cells and neuropeptide-containing
      peripheral nerves. We now show that purified rat peritoneal mast cells contain
      large quantities of N-acetylaspartate (NAA; 747.50 nmol/mg of protein). Mast cell
      levels of NAA were rapidly reduced, by 64.0 and 86.4%, following treatment with
      compound 48/80 and mastoparan, respectively. These secretagogues strongly
      decreased mast cell histamine content over the same time period, suggesting also
      that NAA is stored in secretory granules. The data are the first to show that NAA
      is present in an immune effector cell type. Because NAA may be involved in myelin
      synthesis and glutamyl peptide metabolism, NAA released from mast cells following
      nervous or other stimuli could participate in neuroimmune interactions. Mast
      cells in multiple sclerosis plaques may contribute to the reported elevations in
      brain NAA in this disease.

PMID- 9282959
TI  - Native serotonin 5-HT3 receptors expressed in Xenopus oocytes differ from
      homopentameric 5-HT3 receptors.
AB  - Efficacies of the 5-hydroxytryptamine (serotonin) 5-HT3 receptor (5-HT3R)
      agonists 2-methyl-5-HT, dopamine, and m-chlorophenylbiguanide on 5-HT3R native to
      N1E-115 cells and on homopentameric 5-HT3R expressed in Xenopus oocytes were
      determined relative to that of 5-HT. Efficacies of 2-methyl-5-HT and dopamine on
      5-HT3R native to differentiated N1E-115 cells are high (54 and 36%) as compared
      with their efficacies on homopentameric 5-HT3R-A(L) and 5-HT3R-A(S) receptors
      expressed in oocytes (4-8%). m-Chlorophenylbiguanide does not distinguish between
      5-HT3R in N1E-115 cells and in oocytes. The distinct pharmacological profile of 5
      HT3R native to differentiated N1E-115 cells is conserved when poly(A)+ mRNA from
      these cells is expressed in oocytes. The results indicate that, apart from the
      known 5-HT3R subunits, N1E-115 cells express additional proteins involved in 5
      HT3R function.

PMID- 9282960
TI  - Dopamine transporter is required for in vivo MPTP neurotoxicity: evidence from
      mice lacking the transporter.
AB  - The neurotoxic effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was
      tested on mice lacking the dopamine (DA) transporter (DAT-/- mice). Striatal
      tissue DA content and glial fibrillary acidic protein (GFAP) mRNA expression were
      assessed as markers of MPTP neurotoxicity. MPTP (30 mg/kg, s.c., b.i.d.) produced
      an 87% decrease in tissue DA levels and a 29-fold increase in the level of GFAP
      mRNA in the striatum of wild-type animals 48 h after administration. Conversely,
      there were no significant changes in either parameter in DAT-/- mice.
      Heterozygotes demonstrated partial sensitivity to MPTP administration as shown by
      an intermediate value (48%) of tissue DA loss. Direct intrastriatal infusion of
      the active metabolite of MPTP, 1-methyl-4-phenylpyridinium (MPP+; 10 mM), via a
      microdialysis probe produced a massive efflux of DA in wild-type mice (>320
      fold). In the DAT-/- mice the same treatment produced a much smaller increase in
      extracellular DA (sixfold), which is likely secondary to tissue damage due to the
      implantation of the dialysis probe. These observations show that the DAT is a
      mandatory component for expression of MPTP toxicity in vivo.

PMID- 9282961
TI  - A generalised increase in protein carbonyls in the brain in Parkinson's but not
      incidental Lewy body disease.
AB  - The degeneration of neurones in Parkinson's disease (PD) may involve oxidative
      stress. Previously, increased lipid peroxidation and oxidative DNA damage have
      been reported in parkinsonian substantia nigra. In the present study the protein
      carbonyl assay was used to assess oxidative protein damage in postmortem brain
      tissue from patients with PD and age-matched controls. In brain areas associated
      with PD, such as substantia nigra, caudate nucleus, and putamen, there was a
      significant increase in carbonyl levels. However, increased carbonyl levels were
      also found in areas of the brain not thought to be affected in PD. This perhaps
      suggests that protein carbonyl formation is related to therapy with L-DOPA, which
      can exert prooxidant properties in vitro. Consistent with this possibility, brain
      regions from individuals with incidental Lewy body disease (putative
      presymptomatic PD) showed no rise in carbonyls in any brain areas. Our data show
      that either oxidative protein damage occurs widely but late in PD brain, and/or
      that L-DOPA treatment contributes to protein oxidation.

PMID- 9282963
TI  - Neurohormonal control of gallbladder motility.

PMID- 9282962
TI  - Lipid peroxidation in brain homogenates: the role of iron and hydroxyl radicals.

PMID- 9282964
TI  - High prevalence of duodenal ulcer and gastric cancer in dyspeptic patients in
      Korea.
AB  - BACKGROUND: Although gastric cancer and duodenal ulcer are both related to
      Helicobacter pylori infection, they are mutually exclusive diseases such that
      patients with a history of duodenal ulcer have a markedly reduced risk of
      developing gastric cancer. It has been hypothesized that different strains of H.
      pylori may be related to the different diseases. Our aim was to study the
      prevalence of duodenal ulcer disease and gastric cancer in dyspeptic patients in
      South Korea, a country with a high incidence of gastric cancer. METHODS: The
      study population consisted of consecutive patients between the ages of 20 and 81
      years referred to Guro Hospital's Endoscopic Unit for evaluation of dyspepsia.
      Patients with a history of peptic ulcer or gastric cancer were excluded. Each
      patient underwent endoscopy and completed a detailed questionnaire. Peptic ulcer
      was defined as the presence of an active ulcer, red scar, or white scar. RESULTS:
      One thousand patients were evaluated, and 867 (43% men and 57% women) met the
      entry criteria. The prevalence of peptic ulcer and gastric cancer were 24% and
      7%, respectively. Among peptic ulcer patients, duodenal ulcer was commoner (75%)
      than gastric ulcer or coexistent duodenal and gastric ulcer (21% and 4%,
      respectively). The mean age of duodenal and gastric ulcer patients (45 +/- 14 and
      48 +/- 12 years, respectively) was significantly lower than that of gastric
      cancer patients (59 +/- 11 years) (P < 0.01). Only 44 (7%) of the 597 remaining
      patients had definite endoscopic abnormalities (for example, erosive esophagitis,
      duodenitis, or pyloric deformity). CONCLUSION: Gastric cancer and duodenal ulcer
      were prevalent diagnoses among Korean patients undergoing endoscopy for
      evaluation of dyspepsia. Korea may be the ideal country to investigate the
      relation between specific H. pylori strains and different H. pylori diseases.

PMID- 9282965
TI  - Ranitidine effectively relieves symptoms in a subset of patients with functional
      dyspepsia.
AB  - BACKGROUND: Acid secretion inhibitors are of dubious value to most patients with
      functional dyspepsia but might be effective in a subset. The aims of the trial
      were to compare the effect of ranitidine with that of placebo in selected subsets
      of patients. METHODS: Two hundred and twenty-six patients with functional
      dyspepsia were included in a double-blind multi-crossover (MCO) trial. After 6
      weeks an effect score (Xs) with a range of 0-5 was calculated. They were then
      stratified in accordance with their score and randomized to 4 weeks' double-blind
      treatment with ranitidine or placebo. Overall symptoms were scored on a 100-mm
      visual analogue scale, and the change in score (measured in millimetres) was the
      primary effect measure. RESULTS: Two hundred and six patients completed the
      study. The effect of ranitidine and placebo in the 'responders' (76 patients with
      Xs of 4-5 after the MCO period) was 28 mm and 5 mm, respectively (P < 0.001), and
      in all patients 19 mm and 12 mm, respectively (P < 0.03). No effect was seen in
      'nonresponders' (130 patients with Xs of 0-3 after the MCO period). The clinical
      improvement, as judged by the patients given ranitidine during the last 4-week
      period was statistically significantly different in favour of responders compared
      with nonresponders. We were unable to characterize the responders on the basis of
      demographics, symptoms, and signs. CONCLUSIONS: Ranitidine has a good and
      clinically significant effect in a subset of patients with functional dyspepsia.

PMID- 9282966
TI  - Endoscopic grading of reflux oesophagitis: what observations correlate with
      gastro-oesophageal reflux?
AB  - BACKGROUND: The recognition of minor endoscopic changes is important in correctly
      diagnosing patients with reflux oesophagitis, but the significance of minor
      lesions and what observations to use in endoscopic classification are disputed.
      Our aim was to relate endoscopic observations in reflux oesophagitis with the
      severity of gastro-oesophageal reflux. METHODS: On endoscopy of 64 consecutive
      untreated patients with uncomplicated reflux oesophagitis, accurate records were
      made prospectively of the following variables: axial extent of endoscopic
      changes, width of the lesions, presence of whitish exudate in the lesions, and
      presence and length of a hiatal hernia. Multiple linear regression analysis
      examined which of these factors were significantly related, at the 5% level, with
      gastro-oesophageal reflux as measured at intraoesophageal 24-h pH-metry. RESULTS:
      Presence of whitish exudate and width of lesions were significantly associated
      with severity of gastro-oesophageal reflux. Median fraction of the recording
      period with pH <4 was 5.9% in patients with narrow red lesions, 12.5% in patients
      with narrow, whitish lesions, and 20.3% in patients with broad lesions (P <
      0.0001). The mean duration of reflux episodes was significantly longer and the
      number of nocturnal episodes lasting more than 5 min was significantly higher in
      patients with broad lesions. CONCLUSION: Red spots and streaks, even without
      whitish exudate, are significantly related to pathologic gastro-oesophageal
      reflux. Whitish exudate is related to more severe reflux, and broad lesions to a
      longer mean duration of the episodes. The presence of whitish exudate in lesions
      and the width of the lesions are important observations to use in the
      classification of reflux oesophagitis.

PMID- 9282967
TI  - Lifetime costs of surgical versus medical treatment of severe gastro-oesophageal
      reflux disease in Finland.
AB  - BACKGROUND: Gastro-oesophageal reflux disease (GERD) can be effectively treated
      pharmacologically or surgically. As GERD is often a chronic condition, we
      compared the long-term costs of medical and surgical management. METHODS: The
      medical regimens were ranitidine (150 or 300 mg/day), omeprazole (20 or 40
      mg/day), and lansoprazole (30 mg/day), with costs calculated for total life
      expectancy after diagnosis and for one-third of that time. Costs for open or
      laparoscopic surgery (Nissen fundoplication) included pre- and post-operative
      investigations, sick leave, and calculated financial loss due to fatal outcome.
      RESULTS: Costs were lowest with ranitidine, 150 mg/day, for one-third of the
      patient's lifetime and highest with lifelong omeprazole, 40 mg/daily. The cost of
      open or laparoscopic operation was less than that of lifelong daily treatment
      with proton pump inhibitors or ranitidine, 300 mg daily. CONCLUSION: In Finland,
      antireflux surgery for GERD is cheaper than lifetime treatment with proton pump
      inhibitors.

PMID- 9282968
TI  - The efficacy of a pectin-based raft-forming anti-reflux agent in endoscopy
      negative reflux disease.
AB  - BACKGROUND: Patients with heartburn as their main complaint but normal
      oesophageal mucosa at endoscopy are classified as having endoscopy-negative
      gastro-oesophageal reflux disease (GORD). They have mainly postprandial reflux
      and low total acid exposure and could possibly be managed with a non-systemic
      drug. In such patients we examined the effect of a pectin-based raft-forming anti
      reflux agent (Aflurax (Idoflux)) on the severity of heartburn. METHODS: Patients
      with heartburn but with normal/erythematous oesophageal mucosa (n = 65) were
      randomized to double-blind treatment with two 1200-mg tablets of Aflurax or two
      placebo tablets four times daily for 4 weeks. The main outcome measure was
      heartburn severity on day 15 and day 29. RESULTS: The number of patients scoring
      heartburn severity on day 15 as none, mild, moderate, and severe were 6, 14, 8,
      and 3, respectively, with Aflurax versus 2, 6, 13, and 11 with placebo (P <
      0.05). No further treatment effect was found on day 29. CONCLUSION: Aflurax
      reduces heartburn in patients with endoscopy-negative GORD.

PMID- 9282969
TI  - Cholestyramine influences meal-stimulated pancreaticobiliary function and plasma
      cholecystokinin independent of gastric emptying and food digestion.
AB  - BACKGROUND: Cholestyramine enhances gallbladder emptying and plasma
      cholecystokinin responses to oral ingestion of a mixed meal. It is not known
      whether this effect occurs independently of alterations in gastric emptying or
      maldigestion of nutrients. METHODS: We perfused 15 g of an amino acid meal
      intraduodenally for 60 min in seven healthy volunteers, once with and once
      without cholestyramine. Intraduodenal perfusion of saline with or without
      cholestyramine (6 g/h) was started 60 min before the amino acid meal and
      continued for 2 h. RESULTS: Cholestyramine markedly enhanced the incremental
      plasma cholecystokinin response to the meal from 36 +/- 12 to 139 +/- 25 pmol/l x
      60 min (P < 0.005), incremental amylase output from 2.4 +/- 0.7 to 5.7 +/- 0.7
      kU/h (P < 0.05), and incremental integrated gallbladder contraction from 1948 +/-
      235 to 2840 +/- 189% x 60 min (P < 0.05). CONCLUSION: The enhancing effect of
      cholestyramine on postprandial gallbladder contraction, pancreatic enzyme
      secretion, and plasma cholecystokinin release is not dependent on gastric
      emptying rates or appropriate digestion of nutrients.

PMID- 9282970
TI  - Differences in decorin and biglycan expression in patients with gastric ulcer
      healing.
AB  - BACKGROUND: The small interstitial proteoglycans decorin and biglycan have been
      shown to interact with various extracellular matrix molecules and with
      transforming growth factor-beta. These interactions are proposed to be important
      for tissue repair, as the former interactions may affect the diameter and spacing
      of collagen fibrils, and the latter interaction the proliferation and
      differentiation of cells embedded in the matrix. The aim of this study is to
      localize these proteoglycans in the stomach and to investigate their suitability
      as potential markers of extracellular matrix activity in gastric lesions.
      METHODS: Immunohistochemical techniques and in situ hybridization were used to
      study the phenotypic expression of these two proteoglycans in routinely processed
      specimens of human stomach tissue from 8 patients with gastric ulcer and 10
      healthy control persons. RESULTS: In normal gastric tissue, immunostaining for
      both proteoglycans was found in the interstitium, with a more pronounced staining
      in the pylorus region than in the corpus area. In addition, biglycan showed a
      strong staining of parietal cells. In specimens of healing gastric ulcers a
      larger deposition of decorin throughout scar tissue could be shown, and a higher
      expression of decorin was also found by in situ hybridization. Biglycan was only
      found at the edges of the lesions. CONCLUSION: This study shows for the first
      time the presence of decorin and biglycan in human gastric mucosa. We also showed
      that these proteoglycans may be involved in the gastric ulcer healing processes.

PMID- 9282971
TI  - Effect of colchicine and bisacodyl on rat intestinal transit and nitric oxide
      synthase activity.
AB  - BACKGROUND: Bisacodyl and colchicine affect smooth-muscle contractility,
      intestinal water, and electrolyte transport. Nitric oxide (NO) stimulates
      intestinal electrolyte secretion and has an important role as a mediator of
      intestinal motility. We therefore studied, in rats, the effects of these agents
      on nitric oxide synthase (NOS) activity and gastrointestinal transit. METHODS:
      Rats were treated with bisacodyl (10 mg/kg intragastrically) or colchicine (5
      mg/kg intraperitoneally) with or without pretreatment with ketotifen (1 mg/kg
      intragastrically). Rats were killed after 1, 2, and 4 h. The intestine was
      isolated and rinsed, the mucosa scraped, and NOS activity determined. In all rats
      small-intestinal transit was measured 15 min after intragastric administration of
      charcoal. RESULTS: Bisacodyl (10 mg/kg) and colchicine (5 mg/kg) induced a
      significant decrease in jejunal NOS activity. Pretreatment with the mast cell
      stabilizer ketotifen, which has been shown to attenuate the increased
      permeability induced by NO inhibition, prevented the decrease in colonic and
      jejunal NOS activity induced by bisacodyl and colchicine. Bisacodyl and
      colchicine significantly decreased intestinal transit time. Their effect on
      transit time was similar to that induced by intravenous administration of NG
      nitro-L-arginine methyl ester (10 mg/kg). CONCLUSIONS: It is suggested that the
      effect of bisacodyl and colchicine on intestinal transport is, at least partly,
      mediated through NO inhibition.

PMID- 9282972
TI  - Duodenal juxtapyloric retroperistalsis in the interdigestive state in humans.
AB  - BACKGROUND: The last part of phase III of the migrating motor complex (MMC) is
      characterized by retroperistalsis in the descending duodenum. This study focused
      on MMC-related juxtapyloric peristalsis. METHODS: Antroduodenal manometry was
      performed in 10 healthy subjects. Pressure was recorded in the distal antrum and
      in four consecutive subsegments (DS1-DS4), 15 mm each, in the juxtapyloric
      duodenum. RESULTS: In the period with ongoing antral phase-III activity (early
      duodenal phase III) the antral pressure waves were antegrade, but in the
      juxtapyloric duodenum (DS1) retrograde waves predominated (median, 66%;
      interquartile range (IQR), 33-83%); that is, most duodenal pressure waves were
      directed against the antral ones. More distally, in DS3 and DS4, only 17% and 25%
      (IQR, 0-17, 0-33%, respectively) of the pressure waves were retrograde in this
      period. After the end of antral phase III--that is, in late duodenal phase III-
      the proportion of retrograde pressure waves increased successively to 91.5% (IQR,
      66-100%) in DS2, 74.5% (IQR, 50-100%) in DS3, and 66% (IQR, 8.2-95.8%) in DS4,
      respectively, before the onset of duodenal motor quiescence. In phase II
      antegrade pressure waves predominated (63-76%, medians) in all four duodenal
      subsegments examined. CONCLUSIONS: During the interdigestive phase III the antral
      perstalsis is antegrade, but most juxtapyloric duodenal pressure waves are
      retrograde; that is, antral and duodenal contractions are on a collision course.
      In the proximal part of the descending duodenum the end of duodenal phase III
      shows retroperistalsis after the onset of phase I in the gastric antrum. These
      motor patterns may be important for regulation of the chemical milieu in the
      juxtapyloric area.

PMID- 9282973
TI  - Evaluation of the lactulose/mannitol and 51Cr-ethylenediaminetetraacetic acid/14C
      mannitol methods for intestinal permeability.
AB  - BACKGROUND: We earlier compared the lactulose/mannitol and 51Cr
      ethylenediaminetetraacetic acid (EDTA)/14C-mannitol methods for intestinal
      permeability We have now investigated an increased number of control subjects,
      with special regard to the influence of urinary volume, sex, age, and smoking on
      marker excretion, and patients with intestinal disorders, with special regard to
      correlations between markers. METHODS: The 0- to 6-h urinary excretion of orally
      administered markers was measured in 65 control subjects and in 70 patients.
      RESULTS: In the control group excretion of mannitol and 14C-mannitol (small-pore
      permeability markers) was strongly correlated to urinary volume, whereas such
      correlation was weak for lactulose and absent for 51Cr-EDTA (large-pore
      permeability markers). No sex difference in marker excretion was found, but
      correlation to urinary volume was more pronounced in males. There was a slightly
      decreasing excretion of markers with increasing age, reaching significance for
      51Cr-EDTA and 14C-mannitol; their excretion ratio was unaffected. Smoking did not
      significantly affect marker excretion. In the patient group the excretion of
      large-pore markers tended to be higher and that of small-pore markers to be lower
      than in the control group; correlation between the large-pore markers, between
      the small-pore markers, and between the large-pore/small-pore marker ratios was
      higher than in the control group. CONCLUSIONS: Correction for urinary volume
      substantially reduces variability in small-pore marker excretion. Excretion of
      both types of markers tends to decrease with age, the large-pore/small-pore
      marker ratio remaining unchanged. Smoking does not affect small-intestinal
      permeability. 14C-mannitol is preferred to chemically determined mannitol owing
      to lower test variability.

PMID- 9282974
TI  - Focal inflammatory infiltrations in gastric biopsy specimens are suggestive of
      Crohn's disease. Crohn's Disease Study Group, Germany.
AB  - BACKGROUND: Crohn's disease is a systemic inflammatory disease that may involve
      all regions of the gut. METHODS: Thirty-six patients with Crohn's disease and 36
      age- and sex-matched control patients were prospectively evaluated by upper
      endoscopy. Biopsy specimens were taken from the oesophagus, duodenum, and 10
      locations in the antrum and corpus. RESULTS: Granulomas were found in four
      patients (11.13%) with Crohn's disease but in none of the control patients (P >
      0.5). In 23 of 36 patients (63.9%) with Crohn's disease focal inflammatory
      infiltrations were found, as compared with 7 of 36 (19.4%) of the controls (P <
      0.001). For focal inflammatory infiltrations, an odds ratio of 7.33 (2.55-21.38)
      was calculated, which increased to 20.04 (4.07-98.45) when only specimens from
      the angulus were considered. Helicobacter pylori infection was present in 13 of
      36 controls (36.1%) and in 3 of 36 patients (8.3%) with Crohn's disease (P =
      0.009). CONCLUSION: These data suggest that Crohn's disease is typically
      associated with focal inflammatory infiltrations of the gastric mucosa.

PMID- 9282975
TI  - A multiplex polymerase chain reaction assay for the detection of Mycobacterium
      paratuberculosis DNA in Crohn's disease tissue.
AB  - BACKGROUND: Mycobacterium paratuberculosis is implicated as a possible cause of
      Crohn's disease. However, due to lack of an appropriate diagnostic method, this
      has been a subject of significant controversy. Our aim was therefore to develop a
      multiplex polymerase chain reaction (MPCR) for the detection of M.
      paratuberculosis DNA in Crohn's disease tissue. METHODS: Biopsy samples were
      collected by endoscopic forceps from terminal ileum, and genomic DNA was
      isolated. M. paratuberculosis-specific marker genes were amplified by using the
      present MPCR method. RESULTS: Here we report a new MPCR for detection of M.
      paratuberculosis DNA in Crohn's disease tissue. In this technique two genetic
      markers, IS900 and a newly described specific marker of MP2, were amplified in a
      single tube simultaneously. The method was evaluated using biopsy specimens from
      10 Crohn's disease patients, 6 ulcerative colitis patients, and 21 irritable
      bowel syndrome patients. The patients were characterized by using standard
      clinical and histologic observations. The present MPCR method could not detect M.
      paratuberculosis DNA in the biopsy specimens. However, the marker genes were
      amplified from the samples that were spiked with M. paratuberculosis before DNA
      extraction. The marker genes were also not detected in 10 closely related
      mycobacterial strains and human genomic DNA. CONCLUSIONS: The present MPCR method
      is highly specific and can detect M. paratuberculosis DNA more reliably. These
      findings do not support an aetiologic role of M. paratuberculosis in Crohn's
      disease.

PMID- 9282976
TI  - Effect of suramin on human esophageal cancer cells in vitro and in vivo.
AB  - BACKGROUND: Suramin disrupts several kinds of growth factor receptors. Since
      human esophageal squamous cell carcinoma expresses abundant epidermal growth
      factor receptors (EGFR) and proliferates in an autocrine and paracrine manner, it
      was expected that suramin inhibits tumor growth by disrupting EGFR. METHODS: We
      studied the effect of suramin on the human esophageal squamous cell carcinoma
      cell line KEsC-II in vitro and in an animal model. RESULTS: Cell proliferation
      was stimulated at a low concentration and inhibited at a high concentration of
      suramin in vitro. Since autophosphorylation of EGFR was stronger at the low
      concentration and weaker at the high concentration of suramin compared with the
      control, the effect of suramin was thought to be via phosphorylation of
      receptors. In the animal model tumor growth was significantly stimulated in the
      suramin-treated group compared with the control group, and the BrdU labeling
      index was also higher in the suramin-treated group. CONCLUSIONS: As it was
      impossible to increase the dose of suramin intravenously because of side effects,
      administration of suramin by another method, such as subcutaneous injection
      around the tumor, may increase the concentration of suramin in the tumor tissue
      and promote the anti-tumor effect of suramin.

PMID- 9282977
TI  - Hyponatremia of cirrhosis: role of vasopressin and decreased 'effective' plasma
      volume.
AB  - BACKGROUND: The mechanism(s) of hyponatremia of cirrhosis is not completely
      clarified. Although increased vasopressin activity has been proposed in some
      studies, there have been reports disputing its role in the pathogenesis of
      profound hyponatremia in patients with decompensated liver disease. Methodologic
      flaws and lack of correlation with indices of circulatory dysfunction may have
      contributed to these discrepancies. The aims of the present study were to measure
      levels of vasopressin both in plasma and in urine and to correlate them with the
      volume-dependent hormonal systems of plasma renin activity (PRA) and atrial
      natriuretic factor (ANF). METHODS: Plasma vasopressin, ANF, and PRA were measured
      by radioimmunoassay in 19 patients with cirrhosis, ascites, and severe
      hyponatremia (mean serum sodium, 121.8 mmol/l) and 11 patients with cirrhosis and
      normal serum sodium (mean, 137.6 mmol/l). Vasopressin levels were also assessed
      by radioimmunoassay in urine. RESULTS: Patients with hyponatremia had higher
      plasma and urine vasopressin levels than patients with normal serum sodium
      concentrations (plasma, 2.9 versus 1.0 pg/ml, P = 0.0009; urine, 38.3 versus 12.3
      ng/g creatinine, P = 0.0008). PRA was higher (4.8 versus 1.0 ng/ml/h, P = 0.0004)
      and plasma ANF lower (111.1 versus 148.7 pg/ml, P = 0.01) in patients with
      hyponatremia. CONCLUSIONS: These results indicate that plasma and urine
      vasopressin levels are inappropriately increased in patients with cirrhosis and
      severe hyponatremia. The concomitant increase of PRA and decrease of plasma ANF
      suggest that decreased 'effective' plasma volume generates nonosmotic stimuli for
      vasopressin hypersecretion in these patients.

PMID- 9282978
TI  - Inhibition of nitric oxide modulates the effect of oral arginine supplementation
      in acute liver injury.
AB  - BACKGROUND: Arginine possesses numerous unique and advantageous biochemical and
      pharmacologic properties. We have previously shown that arginine supplementation
      in an acute liver injury model reduces both the extent of the liver injury and
      bacterial translocation. We therefore studied the role of nitric oxide on the
      effects of oral arginine supplementation in acute liver injury, bacterial
      translocation, ileal and cecal mucosal nucleotides, and RNA and DNA, to
      investigate pathogenetic mechanisms. METHODS: Sprague-Dawley rats were divided
      into normal, liver injury control, N-nitro-L-arginine methyl ester (L-NAME),
      arginine, and L-NAME + arginine supplementation groups. Oral supplementation was
      performed daily through a nasogastric tube for 8 days. Acute liver injury was
      induced on the 8th day by intraperitoneal injection of D-galactosamine (1.1 g/kg
      body weight). Twenty-four hours after the liver injury, liver function tests,
      bacterial translocation, and ileal and cecal mucosal nucleotides, RNA, and DNA
      were evaluated. RESULTS: Bilirubin and liver enzymes increased significantly in
      the L-NAME group compared with the arginine group, whereas the liver enzymes
      increased significantly compared with the liver injury control group. In the L
      NAME group the number of bacteria translocated to the portal and arterial blood
      increased significantly compared with all groups. In the arginine group the
      bacteria translocated to the liver and mesenteric lymph nodes decreased
      significantly compared with the liver injury control and L-NAME groups. The ileal
      and cecal mucosal nucleotides, RNA, and DNA in the arginine group increased
      significantly compared with the normal, liver injury, and L-NAME groups.
      CONCLUSIONS: Nitric oxide plays a role in the beneficial effect of the arginine
      supplementation in acute liver injury. It significantly improves the liver damage
      indicated by the increase of liver enzymes when its production was inhibited by L
      NAME. Nitric oxide has a role in bacterial translocation since the number of
      bacteria significantly increased in arterial and portal blood when L-NAME was
      used to inhibit its production. Furthermore, arginine supplementation improved
      mucosal nucleotides, RNA, and DNA in ileum and colon.

PMID- 9282979
TI  - Hyperdynamic circulation of cirrhotic rats: role of substance P and its
      relationship to nitric oxide.
AB  - BACKGROUND: It has been suggested that excessive formation of nitric oxide (NO)
      is responsible for the hyperdynamic circulation observed in portal hypertension.
      Substance P is a neuropeptide partly cleared by the liver and causes
      vasodilatation through the activation of the endothelial NO pathway. However,
      there are no previously published data concerning the plasma level of substance P
      in cirrhotic rats and its relationship to NO. METHODS: Plasma concentrations of
      substance P and nitrate/nitrite (an index of NO production) were determined in
      control rats and cirrhotic rats with or without ascites using an enzyme-linked
      immununosorbent assay and a colorimetric assay, respectively. In addition,
      systemic and portal hemodynamics were evaluated by a thermodilution technique and
      catheterization. RESULTS: Cirrhotic rats with and without ascites had a lower
      systemic vascular resistance (2.6 +/- 0.2 and 3.9 +/- 0.4 mmHg ml(-1) x min x 100
      g body weight, respectively) and higher portal pressure (14.6 +/- 0.6 and 11.3 +/
      1.8 mmHg) than control rats (6.5 +/- 0.3 mmHg x ml(-1) x min x 100 g BW and 6.8
      +/- 0.2 mmHg, respectively, P < 0.05), and cirrhotic rats with ascites had the
      lowest systemic vascular resistance. Plasma levels of nitrate/nitrite
      progressively increased in relation to the severity of liver dysfunction (control
      rats, 2.7 +/- 0.5 nmol/ml; cirrhotic rats without ascites, 5.6 +/- 1.3 nmol/ml;
      cirrhotic rats with ascites, 8.3 +/- 2.2 nmol/ml; P < 0.05). Cirrhotic rats with
      ascites displayed higher plasma values of substance P (57.7 +/- 5.9 pg/ml) than
      cirrhotic rats without ascites (37.9 +/- 3.1 pg/ml, P < 0.05) and control rats
      (30.1 +/- 1.0 pg/ml, P < 0.05). There was no significant difference in plasma
      substance P values between control rats and cirrhotic rats without ascites (P >
      0.05). No correlation was found between plasma levels of substance P and
      nitrate/nitrite (r = 0.318, P > 0.05). CONCLUSIONS: Excessive formation of NO may
      be responsible, at least partly, for the hemodynamic derangements in cirrhosis.
      Although substance P may not participate in the initiation of a hyperdynamic
      circulation in cirrhosis, it may contribute to the maintenance of the
      hyperdynamic circulation observed in cirrhotic rats with ascites.

PMID- 9282980
TI  - Angle of His in the cardioesophageal junction: is it a primordial factor in
      reflux esophagitis?

PMID- 9282981
TI  - Mammalian fertilization: a carbohydrate-mediated event.

PMID- 9282983
TI  - Localization and quantification of binding sites for follicle-stimulating
      hormone, luteinizing hormone, growth hormone, and insulin-like growth factor I in
      sheep ovarian follicles.
AB  - In sheep, growth and development of ovarian follicles beyond 2 mm in diameter is
      acutely dependent on gonadotropin support. As a consequence, following
      hypophysectomy (HPX) or hypothalamic-pituitary stalk disconnection (HPD), growth
      of follicles beyond 2 mm is arrested and all follicles > 2 mm undergo atresia.
      Although administration of exogenous gonadotropins stimulates follicular growth
      and ovulation in HPD ewes, follicles in HPX ewes remain unresponsive unless
      growth hormone (GH) is also given. To determine whether the difference in
      follicular sensitivity to gonadotropins after HPD (gonadotropin sensitive) or HPX
      (gonadotropin insensitive) is related to the distribution and quantity of binding
      sites for FSH, LH, and/or insulin-like growth factor I (IGF-I), binding sites for
      these hormones were localized and quantified using topical autoradiography in
      healthy follicles from control (pituitary-intact), HPD, and HPX ewes. In
      addition, in situ hybridization was performed to localize mRNA for GH and FSH
      receptors. Irrespective of treatment, binding of FSH and mRNA for FSH receptor
      were greatest (p < 0.05) in the membrana granulosa; LH binding was greatest (p <
      0.05) in the theca interna; and IGF-I binding was greatest (p < 0.05) in the
      theca externa. Although the relative number of binding sites for LH did not
      differ among treatments, those for FSH and IGF-I were lower (p < 0.05) in HPD and
      HPX ewes compared to controls. Attempts to quantify binding sites for GH were
      unsuccessful due to high nonspecific binding. However, mRNA for GH receptor was
      most abundant (p < 0.05) in the membrana granulosa and oocytes of small antral
      and preantral follicles. Compared to levels in controls and HPD ewes, the level
      of GH receptor mRNA was lower (p < 0.05) in follicles obtained from HPX ewes. On
      the basis of these data, failure of small antral follicles in HPX ewes to respond
      to exogenous gonadotropins is not due to a reduction in receptors for FSH, LH, or
      IGF-I. The observed reduction of mRNA for GH receptor in the membrana granulosa
      of follicles from HPX ewes provides evidence that GH may play an important role
      in early stages of folliculogenesis and that it is involved in the maintenance of
      sensitivity to gonadotropins.

PMID- 9282982
TI  - Stromal cell progesterone and estrogen receptors during proliferation and
      regression of the decidua basalis in the pregnant rat.
AB  - This study examines the distribution and abundance of progesterone receptors (PR)
      and estrogen receptors (ER) in the decidua basalis (DB) during proliferation
      (Days 8-12 of gestation) and regression (Days 14-21) in the rat. Stromal cells of
      the DB and metrial gland exhibited strong nuclear immunostaining for PR
      throughout gestation. Nuclear localization of ER was detectable only between Days
      8-12. The heavily granulated natural killer cells were always negative for PR and
      ER. DB were dissected between Days 8 and 17 to measure progesterone (P4)-binding
      sites and receptor proteins by Western blotting. The latter revealed four
      specific PR isoforms: B (110 kDa), A1 (90 kDa), A2 (76-82 kDa), and C (60-64
      kDa). Stromal cell nuclei contained more than 50% of P4-binding sites during DB
      proliferation but less than 22% during regression (p < 0.05). PR-A and PR-B
      expression was greatest at proliferative stages (p < 0.05). PR-C increased in
      relative abundance during DB regression. Two ER isoforms of 66 kDa and 49 kDa
      were revealed. The 66-kDa ER, the most abundant form, was maximally expressed
      during proliferation, declining 71% by Day 12 (p < 0.01), whereas the 49-kDa form
      accounted for up to 90% of ER during regression. Northern blot analysis revealed
      three prominent transcripts of approximately 11, 7, and 4 kilobases (kb) for PR
      mRNA, which declined markedly at Days 14 to 17 (p < 0.05), and one of 6.0 kb for
      ER mRNA, which declined markedly on Day 17 (p < 0.05). Our study establishes that
      the DB expresses heterogeneity of receptor message and proteins. We propose that
      preferential expression of receptor isoforms in late pregnancy limits P4 action
      and promotes DB regression in spite of invariant levels of serum P4, P4-binding
      sites, and total receptor protein.

PMID- 9282984
TI  - Expression of aromatase cytochrome P450 protein and messenger ribonucleic acid in
      human endometriotic and adenomyotic tissues but not in normal endometrium.
AB  - To determine whether local estrogen production takes place in endometriotic or
      adenomyotic tissues, in eutopic endometrium from patients with endometriosis or
      adenomyosis, and in normal endometrium, tissue specimens were examined by
      immunohistochemistry, catalytic activity, and mRNA expression for aromatase
      cytochrome P450 (P450arom). P450arom was immunohistochemically localized in the
      cytoplasm of glandular cells of endometriotic and adenomyotic tissues, and of
      eutopic endometrium from patients with the respective diseases, whereas estrogen
      receptors and progesterone receptors were localized in the nuclei of the
      glandular cells and stroma. Aromatase activity in the microsomal fraction of
      adenomyotic tissues was inhibited by the addition of danazol, aromatase
      inhibitors, and anti-human placental P450arom monoclonal antibody (mAb3-2C2) in a
      manner similar to such inhibition in other human tissues. Reverse transcription
      polymerase chain reaction and Southern blot analysis also revealed P450arom mRNA
      in these tissues. However, neither P450arom protein activity nor mRNA was
      detected in endometrial specimens obtained from normal menstruating women with
      cervical carcinoma in situ but without any other gynecological disease. These
      results suggest that at a local level, endometriotic and adenomyotic tissues
      produce estrogens, which may be involved in the tissue growth through interacting
      with the estrogen receptor.

PMID- 9282985
TI  - Effect of repeated collection on semen characteristics of alpacas.
AB  - Semen characteristics of alpacas were studied after repeated collections. Twelve
      adult males were divided into three groups of four each for semen collection
      once, twice, or three times every other day. The duration of copulation; volume
      of ejaculate; pH; motility; sperm concentration (number of sperm/milliliter
      semen); total number of sperm per ejaculate; and percentages of live, normal, and
      abnormal spermatozoa were analyzed by regression analysis. Semen color and
      consistency were analyzed by the chi-square test. Between the first, second, and
      third ejaculations, there were differences (p < 0.05) in sperm concentration;
      percentages of normal spermatozoa and abnormal spermatozoa; sperm with abnormal
      heads and abnormal tails; and consistency (viscous, viscous, and semi-viscous).
      There were no differences (p > 0.05) in ejaculated volume, percentage of live
      spermatozoa, pH, percentage of cytoplasmic droplets, and duration of copulation.
      Some males from which semen was collected on the three-mating schedule ejaculated
      only seminal plasma during the second and third copulation starting on Day 10 of
      the study. There were differences between males (p < 0.05) for most of the
      characteristics studied. In sum, frequency of mating affected some semen
      characteristics that may be important determinants of the fertility of male
      alpacas.

PMID- 9282986
TI  - Immunologic and molecular characterization of an estrogen-dependent glycoprotein
      in the rhesus (Macaca mulatta) oviduct.
AB  - The objective of this study was to detect and characterize a secreted oviduct
      specific glycoprotein (OGP) in the rhesus macaque (Macaca mulatta) and to compare
      the characteristics of this OGP to those previously characterized in baboons and
      women. Oviducts were obtained from untreated ovariectomized rhesus and from
      ovariectomized rhesus either treated with estradiol (E2) for 14 days or treated
      sequentially with E2 for 14 days and then with E2 plus progesterone (P4) for an
      additional 14 days. Segments of oviducts were either fixed for morphological
      analysis, cultured for OGP synthesis and release, or frozen for RNA analysis. The
      proteins present in the culture media were separated by one-dimensional SDS-PAGE,
      and OGP was detected on Western blots using polyclonal antibodies generated
      against the reduced form of baboon OGP or a 17-amino acid segment of the baboon
      core protein. Cross-reacting antigens were present in the 120-kDa region,
      identical to what was observed for baboon and human OGP. Indirect immunogold
      localization of OGP on thin sections demonstrated specific clustering of gold
      particles over the apical secretory granules of the secretory cells of the
      oviductal epithelium. A cDNA was generated using RT-PCR and 5' and 3' rapid
      amplification of cDNA ends (RACE), and sequenced. The total transcript was 2237
      nucleotides in length plus a poly(A) tail. The largest open reading frame was 624
      amino acids, which would produce a protein of 69.3 kDa. The nucleotide sequence
      was more than 95% identical to the nucleotide sequences of baboon and human OGP.
      Northern blots revealed a single message at 2.4 kilobases (kb) in oviduct samples
      obtained from E2-treated rhesus. This message was absent in oviducts obtained
      from untreated ovariectomized and from sequential E2 plus P4-treated rhesus
      macaques. In summary, the rhesus oviduct synthesizes and secretes an OGP in the
      presence of E2 that is immunologically and structurally similar to the baboon and
      human OGP. The presence of a highly homologous glycoprotein in several primates
      suggests a similar function for OGP in the reproductive process.

PMID- 9282987
TI  - Sequence of complementary deoxyribonucleic acid encoding bonnet monkey (Macaca
      radiata) zona pellucida glycoprotein-ZP1 and its high-level expression in
      Escherichia coli.
AB  - Zona pellucida (ZP) glycoproteins have been proposed as candidate antigens for
      immunocontraception. Studies on this potential use can be facilitated by the
      availability of recombinant proteins. A cDNA lambda gt11 library was constructed
      using poly(A)+ mRNA isolated from bonnet monkey (Macaca radiata) ovaries and was
      screened for bonnet monkey ZP1 using a 404-basepair (bp) human ZP1 fragment
      (nucleotides 818-1221) as probe. Bonnet monkey ZP1 cDNA comprises 1617
      nucleotides and encodes a polypeptide of 539 amino acid residues that share 92.0%
      identity with human ZP1. The major difference between bonnet monkey ZP1 and human
      ZP1 is the deletion of a 28-amino acid domain (amino acid residues 100-127
      corresponding to human ZP1). An internal fragment (1317 bp) of bonnet monkey ZP1,
      excluding the N-terminus signal sequence and the C-terminus transmembrane-like
      domain, was amplified by polymerase chain reaction. The amplified Sac I and Kpn I
      restricted fragment was cloned in a frame downstream of the T5 promoter under the
      lac operator control for expression in the pQE-30 vector. Recombinant ZP1 (r-ZP1)
      was expressed as a polyhistidine fusion protein in Escherichia coli strains
      SG13009[pREP4] and ompT and Ion protease-deficient BL21 (plysS). SDS-PAGE
      analysis and immunoblotting with a murine monoclonal antibody, MA-410 (raised
      against porcine ZP3alpha--a homologue of bonnet monkey ZP1--and cross-reactive
      with bonnet monkey zona pellucida), revealed major bands of 51 and 40 kDa besides
      truncated fragments. Optimum expression of r-ZP1 was observed at 0.5 mM isopropyl
      beta-D-thiogalactopyranoside (IPTG). Immunization of male rabbits with r-ZP1
      purified on nickel-nitrilotriacetic acid (NTA) resin under denaturing conditions
      and of female rabbits with r-ZP1 conjugated with diphtheria toxoid-generated
      antibodies reactive with r-ZP1 in ELISA. Moreover, immune sera, when tested by
      indirect immunofluorescence on bonnet monkey ovarian sections, showed positive
      fluorescence with zona pellucida. The information on the sequence of bonnet
      monkey ZP1 and the availability of the recombinant protein will help toward
      better understanding and evaluation of the contraceptive potential of homologous
      immunization in a nonhuman primate model.

PMID- 9282988
TI  - Reduction of sperm cholesterol:phospholipid ratio is a possible mechanism for
      enhancement of human sperm binding to the zona pellucida following incubation
      with phosphatidylcholine liposomes.
AB  - TEST (TES (N-tris[hydroxymethyl]methyl-2-aminoethanesulfonic acid) and Tris) yolk
      buffer (TYB) has recently been shown to improve the binding capacity of
      spermatozoa to zona pellucidae. The present study had two objectives: 1) to
      elucidate which component(s) of TYB dominates this effect and 2) to define the
      responsible mechanism. Sperm samples obtained from subfertile men were incubated
      for 2 h in either TYB or media containing egg yolk lipoproteins or phospholipids.
      After incubation, sperm binding was tested by the hemizona assay. Yolk
      lipoprotein-treated spermatozoa bound hemizonae with efficiency equal to that of
      the spermatozoa incubated in control medium. Conversely, incubation of
      spermatozoa in media containing either TYB, yolk-phospholipids, or pure
      phosphatidylcholine (PC) resulted in a 2- to 3-fold increased binding capacity (p
      < 0.01). A close correlation was found between the effect of yolk-phospholipids
      and TYB on the binding capacity of the same sperm samples, compared to
      spermatozoa incubated in control medium. Incubation of spermatozoa in yolk
      phospholipid medium caused a dose-dependent increase of sperm binding capacity (p
      < 0.05). Treatment of sperm samples with 1 mg/ml or more of purified PC
      preparation also resulted in a reduction of the sperm cholesterol:phospholipid
      molar ratio. Significant correlations between the effects of the treatments on
      sperm cholesterol: phospholipid molar ratio and sperm binding were obtained with
      yolk-phospholipids (r = -0.55) or 1 mg/ml purified PC (r = -0.61). We conclude
      that 1) the enhanced binding capacity of human spermatozoa following TYB
      treatment is probably due to yolk-phospholipids, mainly egg yolk PC; and 2) it
      appears that the enhanced binding capacity of human spermatozoa following
      treatment with egg yolk-containing media may be a result of the reduction of the
      cholesterol:phospholipid molar ratio in the sperm cells.

PMID- 9282989
TI  - Corticotropin-releasing hormone stimulates the expression of the steroidogenic
      acute regulatory protein in MA-10 mouse cells.
AB  - We have previously demonstrated that corticotropin-releasing hormone (CRH)
      treatment of MA-10 mouse Leydig tumor cells results in a dose-dependent
      stimulation of progesterone production. In view of this observation we wished to
      determine the effects of CRH on the synthesis of the steroidogenic acute
      regulatory (StAR) protein in these cells. StAR is a steroidogenic tissue
      specific, hormone-induced, rapidly synthesized protein previously shown to be
      involved in the acute regulation of steroidogenesis, probably by promoting the
      transfer of cholesterol to the inner mitochondrial membrane and the cytochrome
      P450 side-chain cleavage enzyme. Treatment of MA-10 cells with the cAMP analogue
      dibutyryl cAMP (dbcAMP) resulted in a dose- and time-dependent increase in the
      levels of StAR protein that reached a maximum at 800 microM dbcAMP and within a
      time period of 6 h. Further, treatment of MA-10 cells with CRH also resulted in a
      dose-dependent increase in the synthesis of the StAR protein with a maximal
      response observed at 1 microM. Slightly different from that observed with dbcAMP,
      the maximal response to 1 microM CRH was seen at 4 h following stimulation. These
      results indicate that the observed increase in steroid production in response to
      CRH in MA-10 Leydig tumor cells is similar to that previously seen with trophic
      hormone stimulation acting through the cAMP second messenger pathway, and that it
      occurs as a result of an increase in the synthesis of the StAR protein.

PMID- 9282990
TI  - Ratio of inner cell mass and trophoblastic cells in blastocysts derived from
      porcine 4- and 8-cell embryos and isolated blastomeres cultured in vitro in the
      presence or absence of protein and human leukemia inhibitory factor.
AB  - In this study we investigated effects of developmental stage at onset of
      individual in vitro culture on the progress of development in intact embryos and
      individual blastomeres derived from 4-cell and 8-cell porcine embryos (referred
      to as 1/4 and 1/8, respectively), the necessity of serum or BSA supplementation
      in culture media for embryos and blastomeres (in contrast to development in a
      defined medium), and the role of two concentrations of human leukemia inhibitory
      factor (hLIF) on development of blastomeres and embryos. More (p < 0.05) 1/4
      blastomeres developed to the blastocyst stage than did 1/8 blastomeres. In the
      serum-supplemented medium, the percentage of inner cell mass (ICM)/total cells in
      8-cell- and 1/8-derived blastocysts was higher (p < 0.05) than that in 4-cell-
      and 1/4-derived embryos. Development to blastocysts was similar in BSA
      supplemented and defined medium as compared to that in serum-enriched medium in
      intact 4-cell and 8-cell embryos, and 1/4 blastomeres. More (p < 0.05) 1/8
      blastomeres developed to the blastocyst stage in serum-supplemented medium than
      in defined medium. The high hLIF concentration (1000 IU/ml) decreased (p < 0.05)
      blastocyst development in 1/4 blastomeres in defined medium, but fewer
      blastocysts (p > 0.05) lacked an ICM (blastocyst-like vesicles) than in defined
      medium without hLIF. It is concluded that 1) porcine intact embryos and isolated
      blastomeres can be cultured individually in defined medium up to the blastocyst
      stage from the 4-cell stage onwards; 2) more 1/4 isolated blastomeres develop to
      blastocysts with more total cells but with a lower ratio of ICM to total cells
      than blastocysts derived from 1/8 blastomeres; 3) the effects of hLIF are
      dependent on proteins present in the culture medium and on the embryonic stage;
      and 4) in defined medium, high concentrations of hLIF are inhibitory to
      blastocyst formation, but fewer blastocyst-like vesicles are formed. The defined
      culture system employed in this study allows examination of the effects of growth
      factors or cytokines in porcine early embryonic development.

PMID- 9282991
TI  - Expression of immunoglobulin superfamily cell adhesion molecules on murine
      embryonic stem cells.
AB  - The expression of cell adhesion molecules of the Ig superfamily (Ig-CAM) were
      examined on embryonic stem (ES) cells during culture in vitro. ES cells
      maintained an undifferentiated phenotype when cultured in the presence of
      leukemia inhibitory factor (LIF) or with fibroblast feeder cells; > 90% of cells
      reacted positively to an antibody (ECMA-7) that marks undifferentiated ES cells.
      Using flow cytometry, high concentrations of ICAM-1, VCAM-1, and NCAM antigens
      were detected on undifferentiated ES cells, but their specific receptors, Mac-1,
      LFA-1, and VLA-4, were not detected. There was also no class I or II major
      histocompatibility complex (MHC) antigen expression. The ICAM-1 expressed was
      functional, since anti-ICAM-1 significantly (p < 0.0001) blocked ES cell
      lymphocyte binding. Ig-CAM and MHC-1 expression on undifferentiated ES cells was
      not up-regulated by treatment of cells with interferon-gamma (IFN-gamma), tumor
      necrosis factor alpha, or flavivirus infection, agents that up-regulate these
      molecules in other embryonic cell types. Twelve hours after LIF withdrawal, ICAM
      1 and NCAM expression decreased significantly, while VCAM-1 was undetectable.
      However, morphology and ECMA-7 expression remained unchanged. Similar patterns of
      expression were seen on ES cells maintained on fibroblast feeder cells. This
      suggests that LIF or other cytokines may maintain the expression of Ig-CAMs on
      undifferentiated cells. Differentiation was induced by dimethyl sulfoxide
      treatment for 14 days. Cells changed from a colony-forming to a monolayer
      morphology, and approximately 60% of the cell population no longer expressed ECMA
      7. In these cells, VCAM-1 was undetectable and ICAM-1 and NCAM had declined to
      low levels. In these differentiated cells, ICAM-1 and MHC-1 were inducible by IFN
      gamma. This study suggests that the pattern of expression of the Ig-CAMs in ES
      cells may have a role in defining the phenotype of differentiated and
      undifferentiated cells.

PMID- 9282992
TI  - Regulation of oxytocin receptors in bovine granulosa cells.
AB  - It is reported that oxytocin (OT) receptors in bovine granulosa cells decrease in
      concentration during follicular development. However, the factor or factors that
      regulate OT receptors are not known. In the present study, we evaluated hormonal
      control of OT receptors in bovine granulosa cells obtained from small antral
      follicles (3-5 mm in diameter). Granulosa cells were cultured for 48 h and
      exposed to FSH, LH, progesterone, and/or estradiol-17beta (estradiol) in the
      final 15 h of culture. The relative binding of OT decreased to 63% of the control
      value following treatment with FSH (100 ng/ml). The inhibitory effect of FSH was
      mimicked by an adenylate cyclase activator, forskolin. In contrast, estradiol
      (10(-7) M) increased the number of OT receptors by 77% compared with that in
      untreated controls, without changing binding affinity. The effects of estradiol
      were dose dependent and were diminished by an estradiol antagonist, tamoxifen
      (10(-6) to 10(-5) M). Although tamoxifen (10(-5) M) alone did not change OT
      binding, the stimulatory effects of 10(-9) M and 10(-8) M estradiol were
      inhibited by treatment with tamoxifen (10(-5) M). Furthermore, when the granulosa
      cells were exposed to FSH (10 ng/ml) and estradiol (10(-10) to 10(-7) M) in
      various combinations, estradiol inhibited the reduction of OT receptors by FSH.
      On the other hand, LH and progesterone did not affect OT binding in the cultured
      granulosa cells. Additionally, OT secretion from cultured granulosa cells was not
      changed by any treatment used in the present study. These findings suggest that
      both FSH and estradiol are significant regulators of OT receptors in granulosa
      cells during follicular development. FSH might down-regulate OT receptors in this
      phase, and the inhibitory effects of FSH are mediated by the adenylate cyclase
      cAMP-protein kinase A system. Furthermore, estradiol seems to play a role in
      neutralizing the effects of FSH.

PMID- 9282993
TI  - Evidence for the presence of the platelet-activating factor receptor in the CFW
      mouse preimplantation two-cell-stage embryo.
AB  - Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine; PAF),
      a potent signaling phospholipid, has a significant role in preimplantation embryo
      development. CFW mouse embryos respond to PAF with improved development and
      implantation rates. PAF's signal transduction mechanism in other cell types is
      receptor mediated. However, embryonic mRNA for the PAF receptor has not been
      detected. The study objectives were to determine the presence of PAF receptor
      mRNA in CFW mouse two-cell embryos by reverse transcription (RT)-polymerase chain
      reaction and Northern blot analysis and to ascertain the effect of PAF on
      intracellular calcium levels (a receptor-mediated event). Total RNA was purified
      by acid-phenol extraction and ethanol precipitation. Complementary DNA was
      synthesized by RT. RNA was primed with oligo-dT plus PAF receptor-specific primer
      (3' to 5') at 42 degrees C for 60 min, 95 degrees C for 10 min, and 5 degrees C
      for 5 min. The RT product was amplified with Taq polymerase and PAF receptor
      specific primer (5' to 3') at 94 degrees C for 5 min and 54 degrees C for 5 min
      for one cycle, and at 72 degrees C for 3 min, 93 degrees C for 90 sec, and 61
      degrees C for 150 sec for 30 cycles followed by 72 degrees C for 10 min and then
      holding at 4 degrees C. The product was analyzed by agarose gel electrophoresis,
      producing a single band (610 base pairs [bp]), thus demonstrating the presence of
      PAF-receptor mRNA. Sequence analysis of the cloned 610-bp fragment confirmed that
      it is the PAF receptor. Northern blot analysis also confirmed the expression of
      the PAF receptor in the CFW mouse preimplantation two-cell-stage embryo. PAF
      treatment of the two-cell-stage CFW mouse embryo resulted in a fourfold increase
      in intracellular calcium over background levels.

PMID- 9282994
TI  - Progesterone-induced atresia of the proestrous dominant follicle in the bovine
      ovary: changes in diameter, insulin-like growth factor system, aromatase
      activity, steroid hormones, and apoptotic index.
AB  - The objective was to determine whether there were decreases in insulin-like
      growth factors (IGF)-I and -II and increases in low-molecular-mass IGF-binding
      proteins (IGFBPs) in association with an inhibition of aromatase activity (AA)
      and follicular fluid estradiol (E2) production during progesterone (P4)-induced
      dominant follicle atresia in cattle. Twelve cycling cows received a norgestomet
      ear implant at proestrus for 9 days and were assigned to control (n = 3) or P4
      treated (n = 9) groups. Injections of P4 (150 mg, i.m.) were given on Days 3 and
      4; Days 3, 4, and 5; or Days 3, 4, 5, and 6 of the implant period. Controls
      received injections of corn oil on Days 3, 4, 5, and 6. Ultrasonography of the
      dominant follicle and blood sampling were done daily. Unilateral ovariectomy was
      done one day after the last injection. The experiment was repeated with the
      remaining ovary (6 follicles/treatment group). Granulosa cells were cultured with
      radiolabeled testosterone to measure AA. Steroid hormones, IGF-I, and IGF-II were
      measured in follicular fluid by RIA. The follicular fluid IGFBP profile was
      quantified by Western ligand blotting. P4-treated cows showed a drastic reduction
      in AA in the dominant follicles, and follicular fluid E2 was several times lower
      than in controls. Moreover, in P4-treated groups, concentrations of follicular
      fluid IGF-I and IGF-II were lower than in controls. The quantity of low-molecular
      mass follicular fluid IGFBPs increased in P4-treated groups. Accumulation of low
      molecular-mass IGFBPs with a reduction in IGFs may be a mechanism of dominant
      follicle atresia during the bovine estrous cycle.

PMID- 9282995
TI  - Effects of ovarian steroids on uterine growth, morphology, and cell proliferation
      in ovariectomized, steroid-treated ewes.
AB  - Uterine growth, morphology, and endometrial cell proliferation were evaluated in
      intact estrous (EST; Day 0 of the estrous cycle) or luteal (LUT; Day 10 of the
      estrous cycle) ewes or in ovariectomized ewes receiving no hormone (OVX);
      estradiol-17beta (OVX+E); progesterone for 8 (OVX+P8), 30 (OVX+P30), or 60
      (OVX+P60) days; estradiol followed by progesterone (OVX+E+P); or progesterone
      followed by estradiol (OVX +P+E). Uterine weights were greater for EST than for
      LUT ewes, were reduced 2- to 4-fold in OVX ewes, and were increased in estradiol
      treated (OVX+E, OVX+E+P, and OVX+P+E) ewes. The effects of estradiol treatment on
      uterine growth in OVX ewes were primarily on cellular hypertrophy rather than
      hyperplasia. Endometrial labeling index (LI) was greater for EST than for LUT
      ewes and was low in OVX ewes. Compared with OVX ewes, OVX+E and OVX+P+E ewes had
      increased LI for all endometrial tissues, whereas OVX+P8 and OVX+E+P ewes had
      increased LI only for luminal epithelium. These data will help us determine the
      mechanisms by which ovarian steroids regulate uterine growth in ewes.

PMID- 9282996
TI  - Effect of in vivo estradiol administration to bilaterally ovariectomized rats on
      in vitro myometrial responsiveness to prostaglandin F2alpha and oxytocin.
AB  - Bilaterally ovariectomized, nonpregnant female CD rats were studied to
      investigate the effect of estradiol treatment on in vitro myometrial
      responsiveness to oxytocin and prostaglandin F2alpha. The first study
      investigated dose-dependent effects. Seven days after ovariectomy rats were given
      a single s.c. dose of corn oil (n = 4) or estradiol (5 microg, n = 5; 15 microg,
      n = 5; 50 microg, n = 4). A second identical injection of corn oil or estradiol
      was administered 24 h after the initial injection. Rats were killed 48 h after
      the first injection. A second study investigated time-dependent effects of
      estradiol treatment. A second group of ovariectomized rats received s.c.
      estradiol (50 microg) seven days after ovariectomy. These rats were killed either
      12 h (n = 5) or 24 h (n = 4) after injection. Full-thickness cross-sections of
      uteri were suspended in vitro in the longitudinal direction in a superfusion
      system. Cumulative concentration-response curves were constructed to oxytocin and
      prostaglandin F2alpha. Both the duration and dose of estradiol treatment
      significantly (p < 0.05) attenuated baseline contractile activity, and the
      maximum myometrial response to oxytocin and prostaglandin F2alpha. Estradiol, in
      a dose-dependent manner, significantly reduced myometrial sensitivity (p < 0.05)
      for oxytocin and prostaglandin F2alpha.

PMID- 9282998
TI  - Cultured human decidual stromal cells express B7-1 (CD80) and B7-2 (CD86) and
      stimulate allogeneic T cells.
AB  - The origin and function of decidual stromal cells (DSC), the main cellular
      component of the decidua, are uncertain. Although the general consensus is that
      they are fibroblastic cells involved in fetal trophoblast nutrition, several
      authors have demonstrated that these cells can carry out immunological functions
      and that at least a subpopulation of them may be of hematopoietic origin. Human
      DSC precursors or predecidual cells (preDSC) purified by expansion in culture
      express a surface phenotype recalling that of dendritic cells. In the present
      study, we show by flow cytometry that these cells also express B7-1 (CD80) and B7
      2 (CD86), two antigens involved in the costimulation of T cells by antigen
      presenting cells. Cultured DSC were also able to stimulate allogenic T cells in
      vitro. Using an immunohistochemical technique, we found that in cryostatic
      sections of early human decidua, CD80 and CD86 were expressed mainly by DSC
      located around the decidual vessels, a location compatible with preDSC rather
      than fully differentiated DSC. Our results suggest that preDSC are involved in
      antigen presentation.

PMID- 9282997
TI  - Regulation of luteinizing hormone-receptor and follicle-stimulating hormone
      receptor messenger ribonucleic acid levels during development in the neonatal
      mouse ovary.
AB  - Normal gonadal development is dependent upon stimulation by the gonadotropic
      hormones, and it is likely that control of ovarian development is regulated by
      expression of gonadotropin receptors. In this study, quantitative changes in LH-
      and FSH-receptor mRNA levels were measured in the ovary during development in
      normal mice and in hypogonadal (hpg/hpg) mice, which lack circulating
      gonadotropins. The relative abundance of alternate transcripts encoding LH and
      FSH receptors was also determined. Results show that shortened transcripts of the
      receptors were abundant at all ages. Full-length transcripts of the LH receptor
      were not detectable until postnatal Day 5 although shortened transcripts encoding
      the extracellular domain of the receptor were present from birth. Between Days 5
      and 7, LH-receptor transcript levels showed a marked increase in normal animals
      but no change in hpg/hpg animals. FSH-receptor transcripts encoding all domains
      of the receptor were detectable at low levels at birth, increased in
      concentration between Days 3 and 5, and peaked at Day 10. In hpg/hpg animals, FSH
      receptor mRNA levels were normal up to Day 7 but failed to increase thereafter.
      These results show that early development of both LH- and FSH-receptor mRNA
      levels in the ovary is gonadotropin-independent. This coincides with early
      folliculogenesis to the primary stage. Further development of LH-receptor mRNA
      levels is gonadotropin-dependent although FSH-receptor mRNA levels continue to
      increase independently until early secondary follicles are present.

PMID- 9282999
TI  - Interleukin-8 release from human gestational tissue explants: the effects of
      lipopolysaccharide and cytokines.
AB  - Interleukin (IL)-8 is a chemotactic cytokine that has been implicated in the
      etiology of infection-induced and normal human labor. In particular, IL-8 has
      been implicated in the processes of cervical ripening and rupture of fetal
      membranes because of its role in neutrophil activation and release of cellular
      matrix remodeling enzymes. In this study, we tested the hypotheses that IL-8 is
      released locally in the intrauterine environment from human amnion,
      choriodecidua, and placenta, and that IL-8 release from these tissues is
      increased by bacterial endotoxin, lipopolysaccharides (LPS), and inflammatory
      cytokines. IL-8 was released from human amnion, choriodecidual, and placental
      explants, with choriodecidua demonstrating the most abundant release. IL-8
      release was significantly (multiple analysis of variance, p < 0.05) increased by
      LPS in a time- and dose-dependent manner from both choriodecidual and placental
      explants, but not from amnion explants. In addition, IL-1alpha (0.28 nM) and
      tumor necrosis factor alpha (TNFalpha, 10 nM) significantly (Student's t-test, p
      < 0.05) increased IL-8 release from placental explants 2- to 3-fold. These
      studies establish that the amnion, choriodecidua, and placenta are a source of IL
      8 and demonstrate tissue-specific and differential regulation of IL-8 release by
      LPS, IL-1alpha, and TNF-alpha. These data support a role for IL-8 in a cascade of
      inflammatory events initiated by an intrauterine infection and resulting in
      activation of the labor process.

PMID- 9283001
TI  - Evidence for the presence of sodium- and potassium-dependent adenosine
      triphosphatase alpha1 and beta1 subunit isoforms and their probable role in
      blastocyst expansion in the preattachment horse conceptus.
AB  - The unusual hypotonicity of equine blastocyst fluid has prompted us to
      investigate the role of sodium- and potassium-dependent adenosine triphosphatase
      (Na+,K+-ATPase) in the process of fluid accumulation in the horse conceptus. Nine
      mares were used for the experiments. Reverse transcriptase polymerase chain
      reaction was conducted on two sets of five conceptuses recovered between 12 and
      28 days (+/- 1 day) after ovulation. Messenger RNAs encoding the alpha1 and beta1
      subunit isoforms of Na+,K+-ATPase were detected in all embryonic tissues
      examined. Western blot analysis showed that alpha1 and beta1 subunits are both
      present in Day 15 conceptuses. Trophoblast tissues from 19 conceptuses between 8
      and 31 days after ovulation were stained immunohistochemically using primary
      antibodies against the alpha1 and beta1 subunit isoforms of the Na+,K+-ATPase.
      Both isoforms were detected in all sections. Trophoblastic vesicles, prepared
      from 6 conceptuses between 12 and 14 days after ovulation, were used to
      investigate the inhibition of blastocyst expansion with ouabain after collapse
      induced with cytochalasin D. In normal medium there was a mean 3-fold increase,
      and in ouabain (10(-6) M) a mean 3-fold decrease, in the volume of vesicles that
      had been partially collapsed with cytochalasin D. We therefore conclude that,
      despite the hypotonicity of the blastocyst fluid in the early horse conceptus,
      the Na+,K+-ATPase plays a role in its accumulation, as in other species.

PMID- 9283000
TI  - Effects of exogenous recombinant ovine interferon tau on circulating
      concentrations of progesterone, cortisol, luteinizing hormone, and antiviral
      activity; interestrous interval; rectal temperature; and uterine response to
      oxytocin in cyclic ewes.
AB  - Interferon tau (IFN tau) is the conceptus-produced antiluteolytic signal in
      ruminants. Three experiments examined the effects of s.c. administration of
      recombinant ovine (ro)IFN tau on interestrous interval (IEI), oxytocin (OT)
      induced uterine prostaglandin F2alpha metabolite (PGFM) production, rectal
      temperature (RT), respiration rate (RR), and plasma concentrations of
      progesterone, cortisol, LH, and antiviral activity (AVA) in plasma and uterine
      flushings. In experiment I, 20 ewes were treated s.c. with either 0, 1, 2, or 4
      mg/day roIFN tau (0.7 x 10(8) U/mg; 5 ewes/dosage) from Days 11 to 15 of the
      estrous cycle (estrus = Day 0) and were challenged with OT (30 IU) on Day 15.
      Jugular blood samples were collected at -10, 0, 10, 20, 30, 40, 50, and 60 min
      relative to the OT challenge and assayed for PGFM. Recombinant oIFN tau increased
      IEI (16.7, 18.7, and 22.6 +/- 0.6 days for 0, 2, and 4 mg roIFN tau,
      respectively, p < 0.01). Recombinant oIFN tau did not affect peak PGFM response
      to OT (2309 +/- 172 pg/ml; p > 0.1). However, the 4 mg/day dosage delayed the
      time to peak PGFM (32.4 vs. 47.5 +/- 3.4 min; p < 0.01, 0 vs. 4 mg) and resulted
      in approximately 200% higher concentrations of PGFM at 60 min post-OT (0 vs. 4
      mg/day, p < 0.07). Experiment II was similar to experiment I, except that only
      the 0- and 4-mg/day dosages of roIFN tau were administered. Ewes were
      hysterectomized on Day 16, and assay of uterine flushes detected no AVA from ewes
      treated with either 0 or 4 mg/day roIFN tau. In experiment III, 20 ewes were
      treated s.c. with either 0, 2, 4, or 6 mg roIFN tau on Day 12. Blood samples, RT,
      and RR were obtained at frequent intervals for 24 h, and plasma was assayed for
      progesterone, cortisol, LH, and AVA. Plasma AVA, which increased in a dose
      dependent manner, was detectable within 60 min and remained elevated at 24 h
      compared to control values. RT (elevated 0.5-1.0 degrees C), RR, and cortisol
      increased in response to all dosages of roIFN tau, with peak values occurring 150
      180 min postinjection. For all dosages of roIFN tau, plasma progesterone declined
      from 120 to 360 min posttreatment and then returned to pretreatment values by 24
      h (p < 0.01) as compared to controls. Overall, exogenous roIFN tau altered
      uterine PGFM response to OT from a pulse to a gradual and sustained elevation and
      extended IEI with only a transient decline in progesterone and mild hyperthermia,
      effects that are not expected to compromise pregnancy.

PMID- 9283002
TI  - Interactions between the oocyte and cumulus cells in the ovary of the B6.Y(TIR)
      sex-reversed female mouse.
AB  - The XY (B6.Y(TIR)) sex-reversed female mouse is infertile, primarily because of
      the early death of its embryos. We have previously determined that the XY oocyte
      itself, not the surrounding somatic cells, is responsible for its failure in
      postfertilization development. In the present study, we assessed the ability of
      the XY oocyte to regulate granulosa cell differentiation and functions. Oocyte
      cumulus complexes (OCC) were isolated from antral follicles and were cultured in
      the presence of FSH and testosterone. Microsurgical removal of oocytes prevented
      cumulus cell expansion and suppressed estradiol production while it promoted
      progesterone production. Coculture with denuded oocytes from either XX or XY
      ovaries restored cumulus expansion and the endocrine profile observed in intact
      OCC. Morphology of oocytes and OCC in the preantral and antral follicles in situ
      as well as after isolation was compared for XX and XY ovaries. The average area
      of XY oocytes was smaller by 20% only at the preantral stage, whereas the zona
      pellucida layer was thinner by 20% at all stages. Furthermore, the XY oocyte was
      found to be attached to fewer cumulus cells (60% of XX control) in antral
      follicles and isolated OCC. In conclusion, the XY oocyte develops the normal
      ability of regulating granulosa cell differentiation despite its inferiority with
      respect to some morphometric parameters when compared to the XX oocyte.

PMID- 9283003
TI  - Stimulation of brook trout ovarian steroidogenesis by gonadotropins I and II is
      mediated by the cyclic adenosine 3',5'-monophosphate/protein kinase A pathway.
AB  - In teleosts, ovarian steroidogenesis is under the control of two gonadotropic
      hormones, GTH I and GTH II, that are structurally and functionally homologous to
      FSH and LH. The intracellular mechanisms by which GTH I and GTH II stimulate
      steroidogenesis in the teleost ovary are not well understood. The purpose of this
      study was to investigate the involvement of the cAMP/protein kinase A (PKA) and
      protein kinase C (PKC)/Ca2+ signaling pathways in the steroidogenic actions of
      GTH I and GTH II in the ovary of the brook trout (Salvelinus fontinalis). The
      cAMP/PKA pathway mediated the actions of GTH I before germinal vesicle breakdown
      (preGVBD) and GTH II after GVBD and before ovulation (preOV). Experimental
      increases in intracellular cAMP concentration mimicked the steroidogenic effects
      of GTH I and GTH II, and an antagonistic analog of cAMP partially blocked them.
      In addition, GTH I and GTH II stimulated the production of cAMP in preGVBD and
      preOV follicles, respectively. Activation of the PKC/Ca2+ pathway by a phorbol
      ester or a Ca2+ ionophore blocked the GTH I- and GTH II-induced steroid
      production, whereas inhibition of PKC by specific inhibitors potentiated the
      effects of GTH I. These results suggest that the cAMP/PKA signaling pathway
      mediates the stimulatory effects of GTH I and GTH II on steroidogenesis, and they
      also suggest the additional involvement of the PKC/Ca2+ signaling pathway in
      modulating the actions of gonadotropins in brook trout ovarian follicles.

PMID- 9283004
TI  - Molecular cloning and structural analysis of the gene encoding PERF 15 protein
      present in the perinuclear theca of the rat spermatozoa.
AB  - We have cloned the PERF 15 gene, which encodes the most abundant protein of the
      perinuclear theca of rat spermatozoa. PERF 15 is related to the superfamily of
      lipophilic transport proteins. It has a molecular weight of 15,060 and is present
      exclusively in the subacrosomal region of the sperm head. Northern blot analysis
      demonstrated that this gene transcribed PERF 15 mRNA in meiotic and postmeiotic
      cells. The PERF 15 gene contains four exons and three introns. Exon 1 codes for
      amino acids 1-24, exon 2 for amino acids 25-82, exon 3 for amino acids 83-116,
      and exon 4 for amino acids 117-132. The three introns are composed of 2241, 547,
      and 164 base pairs (bp), respectively. The exon/intron boundaries are identical
      to those found in the mouse myelin P2 gene, but there is no resemblance in size
      and sequence between the corresponding introns of the PERF 15 and myelin P2
      genes. Localization of the initiation transcription site by primer extension
      showed that the 5'-untranslated region of this gene is 67 bp upstream of the
      translation initiation site. Primer extension analysis also suggests that there
      is one transcription start site for this gene. Inverse polymerase chain reaction
      generated a 204-bp fragment, located upstream of the translation initiation
      codon, that has some homology with regions of other mammalian genes.

PMID- 9283005
TI  - Follicle-stimulating hormone and intracellular second messengers regulate
      steroidogenic acute regulatory protein messenger ribonucleic acid in luteinized
      porcine granulosa cells.
AB  - Ligand- and second messenger-regulated expression of the gene for steroidogenic
      acute regulatory protein (StAR) was evaluated in luteinized porcine granulosa
      cells. For comparison, cytochrome P450 side-chain cleavage (P450scc) was
      examined. Northern hybridization with homologous cDNA probes demonstrated three
      StAR mRNA species, of 2.7, 1.6, and 0.8 kilobases (kb), with the smallest
      variably present, and a single P450scc band at 1.9 kb. FSH elevated both STAR and
      P450scc messages in a dose-dependent manner over 6 h and continually stimulated
      both over 24 h (p < 0.001). STAR message induction depended on transcription, as
      did that of P450scc. Over 6 h, actinomycin D eliminated constitutive StAR message
      and reduced that of P450scc by two thirds, indicating briefer persistence of
      StAR. Pretreatment with cycloheximide prevented FSH induction of StAR and P450scc
      mRNA, implicating intermediate protein synthesis in expression of both genes.
      Dibutyryl cAMP caused time-dependent increases in StAR and P450 mRNAs over 24 h
      (p < 0.001), indicating the importance of the protein kinase A (PKA) pathway in
      their gene expression. Activation of the protein kinase C (PKC) pathway by a
      phorbol ester eliminated FSH induction of STAR mRNA increases (p < 0.01) while
      only reducing P450scc induction (p < 0.05). Thus, StAR gene expression, as
      reflected in mRNA abundance, is regulated by FSH via the PKA pathway and is
      dependent on transcription and translation. Conversely, the PKC pathway inhibits
      induction of these important steroid synthetic genes in luteinized granulosa
      cells.

PMID- 9283006
TI  - Changes in plasma gonadotropin II and sex steroid hormones, and sperm production
      of striped bass after treatment with controlled-release gonadotropin-releasing
      hormone agonist-delivery systems.
AB  - Spermiating striped bass, a perciform fish, were treated with two controlled
      release gonadotropin-releasing hormone agonist (GnRHa)-delivery systems, and the
      resulting changes in plasma gonadotropin II (GTH II), testosterone (T), 11
      ketotestosterone (11-KT), 17,20beta-dihydroxy-4-pregnen-3-one (17,20beta-P), and
      17,20beta,21-trihydroxy-4-pregnen-3-one (17,20beta,21-P) were correlated with
      changes in milt production and sperm density. GnRHa-delivery systems induced a
      sustained elevation of plasma GnRHa and GTH II for 14 days. Plasma T levels were
      unchanged after GnRHa treatment, while 11-KT levels increased significantly.
      Plasma 17,20beta-P also increased after GnRHa treatment and remained elevated
      compared to levels in controls, while plasma 17,20beta,21-P levels were
      unaffected. Both GnRHa-delivery systems induced many-fold increases in total
      expressible milt, lasting throughout the 14 days of the study. Sperm density
      decreased 2 days after GnRHa treatment, with a subsequent increase by Day 7. This
      study demonstrates that GnRHa-delivery systems induce a sustained elevation of
      plasma GTH II levels in striped bass, resulting in a long-term enhancement of
      milt production. The endocrine changes observed suggest that 11-KT and 17,20beta
      P, but not 17,20beta,21 -P, are mediating the effects of GTH II on spermiation.

PMID- 9283007
TI  - Expression of the c-kit gene is critical for migration of neonatal rat gonocytes
      in vitro.
AB  - Rat gonocytes migrate to the basement membrane during the first postnatal week, a
      change in position crucial for their survival. These cells express the c-kit gene
      from the day of birth through Day 5 in vivo and develop the ability to migrate in
      Sertoli cell-gonocyte cocultures. In this study, we asked whether c-kit
      expression and synthesis of Kit protein are required for pseudopod production by
      gonocytes in vitro. To determine whether gonocyte migration in vitro is
      invariably accompanied by c-kit expression, we quantified percentages of
      gonocytes expressing c-kit with increasing time in vitro and correlated these
      data with pseudopod development by individual cells. We also determined the
      effect of exposure to Kit antibodies on gonocyte migration in vitro, and,
      conversely, asked whether addition of exogenous stem cell factor (SCF), the Kit
      ligand, stimulates pseudopod development. We found that 1) increasing numbers of
      gonocytes express c-kit with increasing time in vitro; 2) once these cells begin
      migrating in vitro, the appearance of a pseudopod on a gonocyte is absolutely
      correlated with kit expression by that cell; 3) incubating cocultures with Kit
      antibodies significantly reduces the number of cells with pseudopods, without any
      detectable decrease in numbers of gonocytes; and 4) addition of exogenous SCF to
      cocultures prepared on Day 5 results in a transient but significant increase in
      the percentage of gonocytes with pseudopods even though we found that Sertoli
      cells in the cultures produce endogenous SCF. Thus, our findings provide evidence
      to support a role for c-kit expression by neonatal gonocytes and, presumably, SCF
      expression by neonatal Sertoli cells in stimulating migration of these germ cells
      in vitro.

PMID- 9283009
TI  - Identification of glucuronan lyase from a mutant strain of Rhizobium meliloti.
AB  - The Rhizobium meliloti M5N1CS (NCIMB 40472) mutant strain wich induces nodule
      formation on alfalfa roots, produces a (1 --> 4)-beta-D-glucuronan partially
      acetylated. During fermentation under specific conditions, the molecular weight
      of the polymer decrease, the presence of polysaccharide degrading enzyme was
      suspected. A glucuronan lyase was identified, this new bacterial lyase produces
      d.p. 4 oligoglucuronans, substituents (acetates) present on the substrate reduced
      the enzyme activity.

PMID- 9283008
TI  - Interactions between follicle-stimulating hormone and growth factors in
      regulation of deoxyribonucleic acid synthesis in bovine granulosa cells.
AB  - Follicle growth is regulated by the combined actions and interactions of
      pituitary gonadotropic hormones and local intraovarian paracrine and/or autocrine
      agents, including the peptide growth factors, insulin-like growth factor-I (IGF
      I), and epidermal growth factor (EGF). The present study was undertaken to
      determine a) whether the previously demonstrated inhibitory effect of FSH on DNA
      synthesis was related to its ability to cause cumulus mucification as a
      differentiated response incompatible with continued proliferation, and b) whether
      increased IGF-binding proteins (IGFBP) secreted in response to FSH competed with
      IGF receptors, thereby inhibiting response to exogenous IGF-I. To determine the
      effects of cumulus mucification in modulating the mitogenic response to IGF-I,
      two other agents that induce cumulus mucification by different mechanisms, EGF
      and dibutyryl cAMP (dbcAMP), were compared with FSH. To determine the possible
      role of IGFBP in modulating the mitogenic response to IGF-I, an IGF-I analogue
      that does not bind to IGFBP, long arg3-IGF-I (LR3-IGF-I), was compared with
      native IGF-I for efficacy in stimulating DNA synthesis in the absence and
      presence of each of the above agonists. Both IGF-I and LR3-IGF-I stimulated
      [3H]thymidine incorporation in cumulus cells to a much greater extent than in
      mural granulosa cells. Incorporation in mural cells was increased by each of FSH,
      EGF, and dbcAMP acting by itself, and in most instances was considerably enhanced
      by the combined action of these agents with each of the IGF-I forms. In contrast,
      the considerably greater stimulatory effect of both IGF-I and LR3-IGF-I on
      cumulus cells was markedly decreased by each of FSH, EGF, and dbcAMP. These
      findings suggest that the inhibition of IGF-I-stimulated DNA synthesis in cumulus
      cells is a consequence of induction of cumulus cell differentiation
      (mucification) by FSH and EGF rather than through competition between IGF-I
      receptor and IGFBP secretion induced by these agents.

PMID- 9283010
TI  - Cell wall metabolism and autolytic activities of the yeast Saccharomyces exiguus.
AB  - Autolytic activities were measured in cell walls prepared from the yeast
      Saccharomyces exiguus. Walls of yeast cells exhibited higher autolytic activities
      directed toward glucans at the exponential phase of growth when compared to cells
      at the stationary phase, while glucanase activities in the soluble extract
      fraction were higher at the stationary phase when compared to exponential phase,
      suggesting an important role of cell wall glucanases in growth of the yeast
      cells. Yeast cell walls also exhibited a substantially high autolytic activity of
      glycoproteins containing mannose throughout growth. These results illustrate the
      diverse metabolism related to functions of yeast cell walls.

PMID- 9283011
TI  - Regulation of cell wall glucanase activities by non-enzymic proteins in maize
      coleoptiles.
AB  - Auxin stimulates cell wall glucanase activities in isolated segments of maize
      coleoptiles with no detectable change in the amounts of the enzymic peptides. To
      disclose the regulatory mechanism for this enhanced growth, we examined the
      possibility that protein interactions account for stimulating cell wall enzyme
      activities. One putative regulatory peptide, an acidic wall protein (AW), was
      separated from the wall protein fractionation profile, and this non enzymic
      protein was able to stimulate both exo- and endoglucanase activities in vitro.
      The results are consistent with the hypothesis that a pertinent glucanase/glucan
      interaction might be facilitated by AW mobilization within the wall in response
      to auxin-treatment.

PMID- 9283013
TI  - Immunological and functional properties of the exudate gum from northwestern
      Mexican mesquite (Prosopis spp.) in comparison with gum arabic.
AB  - A comparison between the fine structural features of exudate gum from mesquite
      (Prosopis spp.) indigenous to NW Mexico and commercial gum arabic from Acacia
      spp. was achieved by means of immunological techniques. Their functional
      properties were compared from the ability to form oil-in-water emulsions and
      encapsulate cold press orange peel essential oil by spray drying. Fine comparison
      of the antigenic compounds in both materials against polyclonal rabbit
      antibodies, showed that the carbohydrate-rich components with slow mobility of
      mesquite gum are closely related to the faster ones of gum arabic. Also, close
      identity was observed for the components in the proteic fraction of both gums.
      Similar tannin concentrations were found in both materials (approximately 0.43%)
      with only dark coloured samples bearing higher amounts (approximately 1.9%). Gum
      arabic retained nearly 100% of the quantity of orange peel essential oil
      emulsified in water before spray drying, while mesquite gum did so for 90.6% of
      the citrus oil. From these results it is believed that mesquite gum might be a
      suitable replacement of gum arabic in arid regions of the world were Prosopis
      trees have widespread occurrence.

PMID- 9283012
TI  - Developmental regulation of polysaccharide metabolism and growth in the primary
      cell walls of maize.
AB  - During development of the intact maize (Zea mays L.) coleoptile a correspondence
      exists between the rate of change in length and fresh weight but these
      parameters, that reflect growth, are all preceded by the accumulation of dry
      weight by the tissue. Coleoptile dry weight increases rapidly for the first 3-4
      days commensurate with tissue formation with evidence for specific biosynthesis
      including the net incorporation into the cell wall of protein and substantial
      deposition of beta-(1,3)(1,4) glucan. After day 4 the extractable wall protein
      and after day 5 the beta-(1,3)(1,4) glucan begin to decline while the deposition
      of glucuronoarabinoxylan continues. Despite the continued incorporation of
      specific polymers into the wall the accumulated mass does not augment the overall
      dry weight. The shifts in polysaccharide distribution with development are
      consistent with what would be expected in terms of changes in the autolytic
      degradation of the wall. Glucan autolysis in isolated cell walls is relatively
      inactive initially then increases to a maximum by day 4 while arabinoxylan
      autolysis undergoes only relatively minor changes. Changes in the extent of wall
      glucan autolysis is proportional to the levels of glucanase activities extracted
      from the cell wall during the developmental sequence. Glucan in walls of the
      first three leaves of the maize seedlings also reflects dynamic turnover in
      correspondence with growth much like that of the coleoptile, suggesting that
      glucan metabolism coincides with growth in other maize tissues. The acceleration
      of glucan turnover mediated by auxin in situ may result from combinations and/or
      interactions of proteins that promote synergistic polysaccharide hydrolysis.

PMID- 9283014
TI  - Influence of growth conditions on barley starch properties.
AB  - Air equilibrated barley starch comprises amylopectin, amylose, lipid and water.
      The structure of amylose and amylopectin, and the proportion of amylose in
      granules is under genetic control and is therefore subject to genotypic
      variation. The amount of lipid (which is essentially all lysophospholipid) is
      similarly under genetic control. Environment and especially environmental
      temperature do, however, have a regulatory effect on the size of starch granules,
      the amylose to amylopectin ratio and the amount of lipid (which is essentially
      all complexed with amylose) within barley starch. High growth temperatures
      probably facilitate amylopectin crystallisation and increase gelatinisation
      temperatures, (and to some extent the enthalpy of gelatinisation), but delay the
      onset and depress the extent of swelling of granules when heated in water.

PMID- 9283015
TI  - Alginate based new materials.
AB  - Present and future applications of alginates are mainly linked to the most
      striking feature of the alginate molecule; i.e. a sol/gel transition in the
      presence of multivalent cations, e.g. Ca2+, almost independent on temperature.
      These very mild conditions, combined with the fact that alginates are highly
      characterised and understood both in the liquid and in the gel phase, makes this
      biopolymer unique compared to other gelling polysaccharides. Only pectins
      resemble alginate in the sol/gel transition behaviour, but this system can hardly
      be said to be as well characterised and understood as the alginates. The
      properties of alginate solutions and gels suggest biomedical and pharmaceutical
      uses. In this paper, the question of the specifications required by a polymer for
      applications in some biomedical areas will be discussed.

PMID- 9283016
TI  - Release of mixed linkage (1-->3),(1-->4) beta-D-glucans from barley by protease
      activity and effects on ileal effluent.
AB  - The behaviour of barley beta-glucans in the upper gut has been assessed using
      ileal effluents recovered from a barley-based test meal. Results have been
      compared to in vitro treatments used to extract beta-glucans. In vitro, exposure
      to endogenous proteases led to a solubilisation of beta-glucan, ranging from 28%
      in the untreated to 83% following NSP isolation. In ileal effluent 60% of the
      beta-glucan was solubilised, similar to the in vitro treatment. However, the
      viscosity of the ileal effluent was low, comparable to a mucin standard. Although
      beta-glucan can be solubilised in the upper gut its viscosity would appear to
      have only a limited potential to affect nutrient bioavailability.

PMID- 9283017
TI  - Atomic force microscopy of plant cell walls, plant cell wall polysaccharides and
      gels.
AB  - Methods developed for the routine imaging of polysaccharides by atomic force
      microscopy (AFM) have been used to image plant polysaccharides from higher plants
      (pectin) and algae (carrageenan). These methods have been extended to image K
      carrageenan association in hydrated films. Finally, AFM has been used to image
      polysaccharide architecture in moist plant cell walls. Simple experimental and
      image processing methods have been used to enhance molecular structure in 'rough'
      cell wall surfaces.

PMID- 9283018
TI  - Polysaccharide hydrolases in germinated barley and their role in the
      depolymerization of plant and fungal cell walls.
AB  - Cell wall degradation is an important event during endosperm mobilization in the
      germinated barley grain. A battery of polysaccharide and oligosaccharide
      hydrolases is required for the complete depolymerization of the arabinoxylans and
      (1 --> 3,1 --> 4)-beta-glucans which comprise in excess of 90% by weight of these
      walls. The (1 --> 3,1 --> 4)-beta-glucan endohydrolases release oligosaccharides
      from their substrate and are probably of central importance for the initial
      solubilization of the (1 --> 3,1 --> 4)-beta-glucans, but beta-glucan
      exohydrolases and beta-glucosidases may be important additional enzymes for the
      conversion of released oligosaccharides to glucose. The latter enzymes have
      recently been purified from germinated barley and characterized. There is an
      increasing body of evidence to support the notion that the (1 --> 3,1 --> 4)-beta
      glucan endohydrolases from germinated barley evolved from the pathogenesis
      related (1 --> 3)-beta-glucanases which are widely distributed in plants and
      which hydrolyse polysaccharides that are abundant in fungal cell walls.
      Arabinoxylan depolymerization is also mediated by a family of enzymes, but these
      are less well characterized. (1 --> 4)-beta-Xylan endohydrolases have been
      purified and the corresponding cDNAs and genes isolated. While the presence of (1
      --> 4)-beta-xylan exohydrolases and alpha-L-arabinofuranosidases has been
      reported many times, the enzymes have not yet been studied in detail. Here,
      recent advances in the enzymology and physiology of cell wall degradation in the
      germinated barley grain are briefly reviewed.

PMID- 9283020
TI  - NMR and the mobility of water in polysaccharide gels.
AB  - An analysis of the possible modes of motion of water molecules in polysaccharide
      gels indicates that the interpretation of NMR results does not require the
      supposition of a class of 'bound water' with highly perturbed motional states.
      There may, however, be water molecules associated with junction zones in the gels
      whose motions are restricted either by incorporation into the molecular secondary
      structure or as interstitial water in crystallites. Hydration and dehydration
      effects as well as the phenomenon of non-freezing water may all be explained
      within a framework of well understood processes. It is concluded that there is no
      requirement to appeal to 'bound water' to explain any of the properties of water
      in polysaccharide gels.

PMID- 9283019
TI  - Structural characterization of three aldobiuronic acids derived from the capsular
      polysaccharide produced by the thermophilic cyanobacterium Mastigocladus
      laminosus.
AB  - This study deals with the chemical characterization of a capsular polysaccharide
      (CPS) produced by a thermal biomass formed by the cyanobacterium Mastigocladus
      laminosus. Acid hydrolysis performed on the purified polysaccharide has led to
      the isolation of several acid-resistant oligosaccharides. Two of them have
      already been reported and assigned as: alpha - GlcA - (1 --> 2) - alpha - GalA -
      (1 --> 2) - Man. and alpha - GlcA - (1 --> 2) - alpha - GalA - (1 --> 2) - beta -
      Man - (1 --> 4) - beta - Gal(1 --> 2) - Rha. In this report, results on the
      isolation and partial purification of three supplementary oligosaccharidic units
      are presented. Gas chromatography-mass spectrometry (GC-MS) and H-nuclear
      magnetic resonance (NMR) spectroscopy investigations allowed them to be assigned
      as three aldobiuronic acids with the following structures: alpha - GlcA - (1 -->
      3) - Gal alpha - GlcA - (1 --> 3) - Fuc alpha - GalA - (1 --> 3) - Fuc.

PMID- 9283021
TI  - Gelling galactans from the algal community of Furcellaria lumbricalis and
      Coccotylus truncatus (the Baltic Sea, Estonia): a structure-property study.
AB  - Extraction of Furcellaria lumbricalis by potassium hydroxide solution shows that
      the maximum gel strength of polysaccharides separated is attained by extraction
      at concentration 0.16 M KOH. Crude extract from this algal species has a
      complicated monosaccharide composition; a drastic increase of gel strength by
      alkaline extraction of the polysaccharide mixture cannot be explained through the
      composition of a major (kappa) fraction described earlier. Alkaline treatment is
      also suitable for accelerating the extraction of polysaccharides from Coccotylus
      truncatus overlaid with thick epithelium. Viscous galactans from C. truncatus are
      more stable to alkali, their composition is simpler and close to iota
      carrageenan. The formation of mixed kappa and iota carrageenan gels as a result
      of simultaneous extraction of both seaweeds causes levelling of theological
      properties of different extraction fractions.

PMID- 9283022
TI  - Inhibition of reduced DP18-maltodextrin and amylose hydrolysis by acarbose:
      kinetic studies.
AB  - Kinetics of inhibition of porcine pancreatic alpha-amylase by acarbose were
      performed using maltodextrin and amylose as substrates. Similar Lineweaver-Burk
      primary plots were obtained. Two mixed non-competitive models are proposed. X-ray
      crystallographic data (Qian, M., Buisson, G., Duee, E., Haser, R. and Payan, F.
      Biochemistry, 1994; 33: 6284-6294) are in support of the mixed non-competitive
      inhibition model which involves abortive complexes. Secondary plots are different
      indicating that in the maltodextrin hydrolysis, one molecule of acarbose is bound
      per amylase molecule, while using amylose as substrate two molecules of acarbose
      are bound. These two kinetically determined binding sites might correspond to the
      two surface sites shown by X-ray crystallography (Qian, M., Haser, R. and Payan,
      F. Protein Science 1995; 4: 747-755).

PMID- 9283023
TI  - Starch granule surface imaging using low-voltage scanning electron microscopy and
      atomic force microscopy.
AB  - High resolution imaging of wheat and potato starch granule surfaces has been
      performed using low-voltage scanning electron microscopy and atomic force
      microscopy. The complimentary images of uncoated granules demonstrate that the
      two starch types possess substantially different surface topologies; potato
      starch has many protrusions (100-300 nm in diameter), above a flatter surface
      containing 20-50 nm structures, whilst wheat starch possesses far fewer
      protrusions and generally has a smoother surface composed of approximately 20 nm
      structures. The protrusions are believed to be carbohydrate in nature and thus
      represent the ends of amylopectin side-chain clusters at the granule surface.

PMID- 9283024
TI  - Comparative quantitative analysis of sucrose and related compounds using ion
      exchange and reverse phase chromatographic methods.
AB  - Two analytical methods of sugar determination, namely ion exchange chromatography
      on an anionic resin coupled with electrochemical detection, and reverse phase
      chromatography on Nucleosil-NH2 resin equipped with a light scattering detector
      were tested and compared as regards their rapidity, sensitivity and accuracy with
      sucrose, fructose, glucose, raffinose, maltose, arabinose, fucose, rhamnose and
      xylose. Excellent resolution and highly reproducible results were obtained in
      both cases. Greater sensitivity up to the picomolar range was possible however
      only with ion exchange chromatography. Reverse phase chromatography was
      successfully applied to the time course of sucrose hydrolysis under chemical
      (acid) and enzymatic (invertase) conditions. The hydrolysis was monitored by
      determining sucrose degradation and the corresponding formation of glucose and
      fructose.

PMID- 9283025
TI  - Structural studies of CV-70 polysaccharide.
AB  - The goal of this paper is the characterization of the chemical structure of the
      water-soluble polysaccharide, CV-70, produced by bacteria Beijerinckia sp.
      Beijerinckia sp. is a genus of gram-negative, aerobic bacteria, usually found in
      sugar cane root. The CV-70 polysaccharide was produced in a fermentation medium
      containing 5% sucrose as the carbon source, tryptose and salts, at 25 degrees C
      [1]. The polysaccharide was hydrolyzed with 2 N trifluoroacetic acid at 100
      degrees C for 16 h, purified, and analyzed by HPLC. Index of refraction was used
      for the detection of sugars. For GC-MS analysis, the CV-70 polysaccharide was
      derivatized through methylation and acetylation. Together with the GC-MS data,
      periodate oxidation studies were used to determine the possible glucosidic
      linkages. Carbon-13 NMR studies were carried out with hydrolyzed and silylated
      samples. Glucose, galactose and fucose were identified as the components in the
      CV-70 polysaccharide, in a 3:1:3 ratio.

PMID- 9283026
TI  - Rheological and thermal characteristics of gel structures from various agar
      fractions.
AB  - The dynamic rheological properties during gelation, phase transition temperatures
      and the enthalpy (deltaH) for melting of junction zones in gel networks of
      different agar fractions were investigated. The results indicated that both
      gelling (Tgel) and melting (Tm) temperatures, storage moduli (G') and the deltaH
      values of agar gels were mainly correlated with their [eta] values, rather than
      with 3,6-anhydro-galactose (3,6-AG) content. Effects of 3,6-AG content on
      increasing G' were observed only for the gels of low concentrations (e.g. 0.8
      g/dl). The concentration dependences of structural strength and structure
      development rate, which were presented by G' and dG'/dt respectively, were found
      to decrease with increasing 3,6-AG content or [eta] value. It is noteworthy that
      influencing extents of 3,6-AG content and [eta] on the above rheological and
      thermal properties vary not only with the concentration examined, but also with
      the stage of gelation process.

PMID- 9283027
TI  - Enzymic analysis of the structure of oxidized potato starches.
AB  - The possibility to use enzymic methods for the analysis of the positions of
      carboxyl and carbonyl groups in sodium hypochlorite oxidized (HO) and hydrogen
      peroxide oxidized (PO) potato starches was investigated. The HO-starch, that
      contained more modified glucosyl residues, possessed a lower beta-amylolysis
      limit and all of the polymer components were resistant to complete hydrolysis as
      judged from gel-permeation chromatograms. In contrast, the PO-starch contained
      24% of apparently unmodified, linear chains that were hydrolysed by beta-amylase.
      After debranching, approximately 30% of the chains in the HO-sample and
      approximately 20% in the PO-sample remained partly resistant to successive beta
      amylolysis.

PMID- 9283028
TI  - Galactomannan from the seeds of Mimosa scabrella: a scale-up process.
AB  - In view of the wide industrial applications of galactomannans as a thickening
      agent, those of Mimosa scabrella (bracatinga), a leguminous tree abundant in
      Southern Brazil, are under investigation. Seeds of bracatinga were processed on a
      pilot plant scale in order to obtain its galactomannan. The process consisted of
      successive milling, enzyme inactivation, aqueous extraction, precipitation of
      polysaccharide, and drying and milling. The product was obtained in 20% yield,
      with characteristics similar to those obtained on the laboratory scale, namely
      mannose:galactose ratio (M:G) 1.1:1.0 and intrinsic viscosity. Considering the
      seed availability in the metropolitan regions of Curitiba, it should be possible
      to obtain 3000 ton/year of this polysaccharide.

PMID- 9283029
TI  - Organisation and association of kappa-carrageenan helices under different salt
      conditions.
AB  - Mixtures of the added salts NaI and CsI can be used to gradually 'tune' the
      propensity of kappa-carrageenan (KC) helices to aggregate in solution. We show
      that this method can be used to resolve the molecular events by which helix
      formation, under certain conditions, leads to gelation. We also present an
      overview of the various states of aggregation and organisation that appear for
      helical KC (non-degraded or ultrasonically degraded) when the NaI/CsI ratio and
      the concentration of KC are varied. A transition to rigid, superhelical rods is
      found above a well-defined fraction of cesium. This transition is reflected in a
      range of experimental measurements, such as cryo-transmission electron
      microscopy, optical rotation, viscometry and small deformation oscillatory
      measurements. The superhelical-rod state also seems essential for the association
      of KC with locust bean gum, and locust bean gum is found to stabilise this state.
      Novel states of KC alone have been found at cesium contents below the transition
      threshold. Non-degraded KC forms weak gels at sufficiently high concentrations (>
      ca. 1%). In contrast, ultrasonically degraded KC forms a chiral nematic liquid
      crystalline phase at sufficiently high concentrations (> ca. 5%) under these salt
      conditions.

PMID- 9283030
TI  - The xylose-rich pectins from pea hulls.
AB  - The hot acid extract of pea hull, HSP, was rich in galacturonic acid, arabinose
      and xylose. It was fractionated by copper precipitation followed by ion-exchange
      chromatography. The copper-soluble fraction represented 26% of HSP and was mostly
      composed of an arabinan with a low degree of branching, some heteroxylans and a
      glucan, probably starch. The copper-precipitate (74% of HSP) contained pectins
      and some residual arabinan, xylan, glucan and mannan. One of the pectic fractions
      was rich in terminal xylose and fucose; it could be partially degraded by endo
      polygalacturonase but not by endo-xylanase and seemed to contain
      xylogalacturonans.

PMID- 9283031
TI  - Chemical and thermal stability of ferulic acid esterase-III from Aspergillus
      niger.
AB  - The stability of ferulic acid esterase III (FAE-III) from Aspergillus niger was
      examined using chemical and thermal denaturation. Thermal denaturation was
      irreversible and the loss of activity was dependent on pH. At 60 degrees C and pH
      6.0, the rate constant of unfolding was 0.76 10(-3)/s, and the change in free
      energy of irreversible inactivation, deltaG*, was 101.9 kJ/mol. Sinapic acid, a
      product of the reaction of methyl sinapate with FAE-III, reduced the rate of
      unfolding (0.66 10(-3)/s at 0.1 mM sinapic acid). Chemical denaturation was
      performed using guanidine hydrochloride. FAE-III was very sensitive to this
      denaturant, and the midpoint of unfolding was 1.38 M guanidine hydrochloride at
      30 degrees C, pH 6.0. The stability of FAE-III is compared to other enzymes.

PMID- 9283032
TI  - Binding of nascent glucuronoxylan to the cell walls of pea seedlings.
AB  - Glucuronoxylan synthesised in vitro by membrane-bound enzymes from etiolated pea
      epicotyls was found to bind to isolated cell walls from the same tissue in a pH
      dependant manner. The binding was maximum at pH 3.5-4.0, and decreased to zero at
      pH 6. The bound glucuronoxylan could be dissociated from the cell walls by
      washing at pH 6, and the binding appeared to be non-covalent. Extraction
      experiments indicated that the glucuronoxylan was binding to hemicellulose in the
      cell-wall. The observed binding may be significant in the process of cell-wall
      assembly in vivo.

PMID- 9283033
TI  - Integration of inulin determination in the AOAC method for measurement of total
      dietary fibre.
AB  - A suitable modification of the standard AOAC method for the measurement of
      dietary fibre is proposed to quantitatively include beta-fructans in the
      determination of the soluble dietary fibre fraction and as a consequence in the
      related total dietary fibre fraction. The standard AOAC method is modified by
      including a preheated commercial inulinase, Novozym SP 230, to the
      amyloglucosidase incubation step. It was previously outlined that this commercial
      inulinase contains some pectolytic activity. It is now demonstrated that a heat
      pretreatment of this enzyme preparation at 60 degrees C for 2 h eliminates this
      pectolytic activity while keeping sufficient activity to hydrolyse all the inulin
      from the soluble fibre fraction.

PMID- 9283034
TI  - Galactans and cellulose in flax fibres: putative contributions to the tensile
      strength.
AB  - The proton spin-spin relaxation time, T2, measured from solid-state NMR,
      indicates a greater rigidity for cellulose than for the adhesive matrix between
      the microfibrils of flax ultimate fibres. Cytochemical and biochemical analyses
      allow the identification of: (1) EDTA-soluble RG I-polymers in the primary walls
      and cell junctions of fibres; (2) long 1 --> 4-beta-D-galactan chains between
      primary and secondary wall layers; and (3) arabinogalactan-proteins throughout
      the secondary walls. These polymers in the adhesive matrix between microfibrils
      and/or cellulose layers ensure that cracks propagate along the matrix rather than
      across the fibres and play an important role in allowing flax fibres to approach
      the tensile strength of advanced synthetic fibres like carbon and Kevlar.

PMID- 9283035
TI  - Xylose-rich polysaccharides from the primary walls of embryogenic cell line of
      Pinus caribaea.
AB  - Embryogenic cell lines of Pinus caribaea were isolated from somatic embryogenesis
      from zygotic embryos. Previous studies showed that the proteins and glycoproteins
      were characteristic of the embryogenic state. In the present work we were seeking
      typical feature in the polysaccharide from the cell walls of embryogenic calli at
      nine days of culture. Sequential extraction with water, ammonium oxalate,
      dimethyl sulfoxide, sodium borohydride and 4.3 M potassium hydroxide revealed
      that the extracted polysaccharides contained high proportions of arabinose and
      significant amounts of xylose. Fractionation of the hydrosoluble polymers on DEAE
      cellulose afforded a xylose-rich fraction (80% xylose, 24% glucose and lower
      properties of fucose and mannose). Methylation analysis and 13C-NMR spectra
      showed that the glycan backbone consisted of beta 1 --> 4 linked xylosyl residues
      Similar study of the fractions extracted respectively with DMSO and 4.3 M KOH
      showed the presence of polydisperse glycoxylans but excluded the presence of
      xyloglucan in significant amount. This could be a characteristic feature of
      embryogenic cells walls of Pinus caribaea or could be typical of cells grown as
      calluses. In the various fractions obtained from DEAE cellulose chromatography of
      the alkaline extract the infrequent occurrence of fucoxylans beside an
      arabinogalactan showed again the unusual nature of the cell wall polymers of this
      embryogenic lines, which seems to differ greatly from those found in the primary
      wall of cells from suspension cultures.

PMID- 9283037
TI  - Extractibility of structural carbohydrates and lignin deposition in maturing
      alfalfa internodes.
AB  - In the present study, we have performed chemical investigations of the stem cell
      walls during internode maturation in order to study the growth dynamics of
      alfalfa and the deposition of the main cell wall components (polysaccharides and
      lignins). Internode cell walls were analysed by chemical fractionation using a
      mild delignification step aiming at sequential removal of polysaccharides and
      lignins. Delignification facilitated the subsequent removal of the xylose-rich
      polysaccharides by NaOH extraction as previously shown. This trend was more
      pronounced in the case of older internodes which have a larger proportion of
      secondary tissues containing syringyl type lignins in contrast to younger ones
      which are mainly composed of primary tissues containing guaiacyl type lignins and
      pectin rich cell walls.

PMID- 9283036
TI  - Physico-chemical properties of carrageenan gels in presence of various cations.
AB  - Phase separation and gelation induced by addition of monovalent and divalent
      cations in iota and kappa carrageenan solutions were investigated as a function
      of the polymer and cation concentrations. Rheological measurements have also been
      carried out at a given polymer concentration. The storage modulus (G') determined
      at a cation/polymer ratio was always higher for kappa- than for iota-carrageenan.
      For iota carrageenan, G' increased slowly with the monovalent salt concentration
      and more quickly with the divalent salt concentration. At the opposite, for kappa
      carrageenan, G' increased more rapidly in the presence of KCl than with calcium
      or copper. Nevertheless for large salt concentrations, G' became independent of
      the type and concentration of cations in the kappa carrageenan solution.

PMID- 9283038
TI  - Glycaemic index concept and metabolic diseases.
AB  - Glycaemic response is not just a function of a compound belonging to the class of
      simple sugars or to the class of starches, or in other words, the size of the
      molecule. Glycaemic response to carbohydrates depends on several factors,
      particularly the chemical nature of the glucids, their origin, their mode of
      preparation, the physical form under which food is consumed, the presence of
      other nutrients (lipids, proteins) and fiber. Glycaemic and insulinemic indexes
      can be used to semi-quantitatively classify types of food as a function of their
      power to raise glucose and insulin levels. A recent mera-analysis of a dozen
      clinical trials has shown the utility of replacing high glycaemic index
      carbohydrates with low glycaemic index carbohydrates to improve different
      metabolic parameters in patient subgroups at risk (DDM, NIDDM, high triglyceride
      levels, etc.). In addition, this knowledge can eliminate the need to
      systematically forbid all sugars and sweet foods, and thus in an apparent
      paradox, to respect both food behavior and enjoyment alongside compliance with
      dietary advice.

PMID- 9283040
TI  - Heterogeneity of DNA distribution pattern in renal tumours.
AB  - The presence of intratumoural heterogeneity in DNA distribution patterns has been
      accepted. However, most previous studies have not taken this fact into
      consideration. The value of DNA cytometry depends on its reproducibility. This
      could be influenced by heterogeneity failure. The aim of the present study is to
      evaluate intratumoural heterogeneity in renal cell cancer. A sample of 22 tumours
      of the kidney was investigated by means of static DNA cytometry: 21 tumours were
      carcinomas, one was an angiomyolipoma. Probes from seven different locations of
      each tumour were Feulgen-stained and measured. The variability of DNA features
      was determined and correlated with histological grade and type and with tumour
      size. There was considerable intratumoural heterogeneity with respect to DNA
      distribution pattern in 45% of the tumours. Additional non-diploid tumour
      stemlines and deviation of computed DNA features could be found in several cases
      by measuring more than one slide per tumour. A correlation between tumour
      heterogeneity, grading or typing, and tumour size could not be found. Because
      these DNA parameters could serve as the foundation of a risk-adapted treatment,
      tumour heterogeneity could have clinical consequences. Based on the results of
      this study we suggest measuring at least three slides per tumour to avoid
      misinterpretation of DNA measurements in renal cell cancer.

PMID- 9283039
TI  - Lymphoid infiltrates in B cell non Hodgkin's lymphoma: comparing nuclear
      characteristics between lymph node and bone marrow; and evaluating diagnostic
      features of bone marrow infiltrates in paraffin embedded tissues.
AB  - Distinguishing non Hodgkin's lymphoma from benign lymphoid aggregates in bone
      marrow is well recognised to be difficult. Our objective was to evaluate nuclear
      morphology, and to perform morphometry on benign and neoplastic lymphoid
      infiltrates, to establish if objective criteria were of value in the diagnosis of
      neoplasia. By comparing neoplastic infiltrates in bone marrow with infiltrates in
      lymph nodes, the validity of grading non Hodgkin's lymphoma on the basis of bone
      marrow histology alone was assessed. 82 cases of B cell non Hodgkin's lymphoma
      (44 low grade and 38 high grade), known to have both lymph node and bone marrow
      involvement at the time of presentation, were compared with bone marrow trephines
      containing reactive lymphoid infiltrates. The results suggest that in paraffin
      embedded tissue from bone marrow trephines, nuclear morphology, nuclear area and
      the nuclear contour index cannot, in most cases, be used to distinguish reactive
      from neoplastic lymphoid infiltrates although mean nuclear area supports a
      diagnosis of a neoplastic infiltrate if it can be shown that the nuclei are
      larger than would be expected in reactive infiltrates. Such differences are
      subtle and often not appreciable without the use of quantitative techniques. The
      frequent occurrence of discordant infiltrates in high grade lymphomas means
      grading of lymphoma on the basis of bone marrow appearances is often unrealistic.

PMID- 9283042
TI  - Detection of malignancy associated changes in cervical cell nuclei using feed
      forward neural networks.
AB  - Normal cells in the presence of a precancerous lesion undergo subtle changes of
      their DNA distribution when observed by visible microscopy. These changes have
      been termed Malignancy Associated Changes (MACs). Using statistical models such
      as neural networks and discriminant functions it is possible to design
      classifiers that can separate these objects from truly normal cells. The correct
      classification rate using feed-forward neural networks is compared to linear
      discriminant analysis when applied to detecting MACs. Classifiers were designed
      using 53 nuclear features calculated from images for each of 25,360 normal
      appearing cells taken from 344 slides diagnosed as normal or containing severe
      dysplasia. A linear discriminant function achieved a correct classification rate
      of 61.6% on the test data while neural networks scored as high as 72.5% on a cell
      by-cell basis. The cell classifiers were applied to a library of 93,494 cells
      from 395 slides, and the results were jackknifed using a single slide feature.
      The discriminant function achieved a correct classification rate of 67.6% while
      the neural networks managed as high as 76.2%.

PMID- 9283041
TI  - Opening the black box: the relationship between neural networks and linear
      discriminant functions.
AB  - Over the last ten years feed-forward neural networks have become a popular tool
      for statistical decision making. During this time, they have been applied in many
      fields, including cytological classification. Neural networks are often treated
      as a black box, whose inner workings are concealed from the researcher. This is
      unfortunate, since the inner workings of a neural network can be understood in a
      manner similar to that of a linear discriminant function, which is the standard
      tool that researchers use for decision making. This paper discusses feed-forward
      neural networks and some methods to improve their performance for classification
      problems. Their relationship to discriminant functions will be examined for a
      simple two-dimensional classification problem.

PMID- 9283043
TI  - DNA measurement of overlapping cell nuclei in thick tissue sections.
AB  - The paper describes an improved image analysis procedure for measuring the DNA
      content of cell nuclei in thick sections of liver tissue by absorption
      densitometry. Whereas previous methods only permitted the analysis of isolated
      nuclei, the new technique enables both isolated and overlapping nuclei to be
      measured. A 3D segmentation procedure determines whether each object is an
      isolated nucleus or a pair of overlapping nuclei; in the latter case the combined
      optical density is redistributed to the individual nuclei. A selection procedure
      ensures that only complete nuclei are measured. The method has been tested on
      specially-prepared Feulgen-stained 20micro sections of normal liver tissue. The
      overall distribution of the nuclear DNA measurements shows well-defined diploid
      and tetraploid peaks, with coefficient of variations of less than 10%. Similar
      distributions were obtained from both the isolated nuclei and overlapped nuclei
      sub-populations.

PMID- 9283044
TI  - Sequential assessment of cell cycle S phase in flow cytometry: a non-isotopic
      method to measure lymphocyte activation in vitro.
AB  - Lymphocyte multiplication can be induced in vitro by mitogens or specific
      antigens, and is usually measured using isotopic methods involving tritiated
      thymidine. Cellular proliferation can also be analyzed by flow cytometry
      techniques based on cell cycle analysis through the measurement of DNA content.
      We applied this method to lymphocytes from 113 individuals, to evaluate
      lymphocyte proliferation after stimulation in vitro by a mitogen
      (phytohaemagglutinin, PHA) or a recall antigen (tetanus toxoid), using a kinetic
      approach with four points sequential measurements of the S and G2 phases over six
      days of culture. The proportion of cells in S phase after PHA stimulation was
      significantly higher than in controls overall and as early as on day three of the
      culture. Activation with a recall antigen significantly induced increasing S
      phase cell proportions up to day six. These data suggest that flow cytometric
      assessment of the S phase could be a useful alternative to isotopic methods
      measuring lymphocyte reactivity in vitro.

PMID- 9283045
TI  - The interactive language of the hypothalamus for the gonadotropin releasing
      hormone (GNRH) system.
AB  - The enormous diversity in neurochemical signals employed within the network of
      afferents to GnRH neurons is well-documented. An examination of novel and
      accumulating knowledge on the operation of these messengers indicates the
      presence of an interactive language governing GnRH secretion. The basic
      operational structures identified to date to affirm this interactive form of
      communication summarized in this review are the following: (i) the demonstration
      of interconnections within various components of the afferent network; (ii)
      coexistence and possible co-release of excitatory and inhibitory
      neurotransmitters/neuromodulators; (iii) co-action of various messengers at
      synaptic targets, and (4) modulation by gonadal steroids of the synthesis and
      release of signals and their receptors, and induction of synaptic plasticity for
      the timely relay of signals for GnRH secretion. Unraveling the molecular sequelae
      that promote this interactive communication to elicit periodic GnRH secretion is
      now a new challenge.

PMID- 9283046
TI  - Neuroendocrine and behavioral responses and brain pattern of c-fos induction
      associated with audiogenic stress.
AB  - The present study determined simultaneously the behavioural, neuroendocrine and
      regional brain activity, using semi-quantitative analysis of c-fos mRNA
      induction, produced by 30 min of auditory stimulation at different white noise
      intensities (background 60 dB, 70, 80, 90 and 105 dBA), in rats. Only the highest
      noise intensities (90 and 105 dB) significantly increased corticosterone release
      after 30 min stimulation. Behaviourally, the 105 dB noise condition reliably
      reduced overall activity, and moderate noise intensities (70 and 80 dB) increased
      sleeping time. Three distinct patterns of c-fos mRNA induction were observed.
      First, following exposure to the experimental cages, a wide pattern of brain
      activation was obtained in experimental animals irrespective of noise intensity
      presentation, compared to the naive rats. Second, a number of auditory structures
      (cochlear nuclei, superior olivary complex, nuclei of the lateral lemniscus,
      inferior colliculus and the medial division of the medial geniculate body)
      displayed a clear intensity-dependent increase in c-fos induction. Third,
      compared to all other conditions, the stressed rats (90 and 105 dB conditions)
      displayed significantly higher c-fos induction in relatively few areas.
      Particularly intense c-fos induction was observed in the bed nucleus of the stria
      terminalis, especially its anterior medial and ventral aspects, the
      septohypothalamic nucleus, the ventral lateral septum, the ventral portion of the
      dentate gyrus, a number of hypothalamic nuclei including the lateral preoptic
      area, the medial preoptic nucleus and the paraventricular nucleus, the median
      raphe and the pedunculopontine tegmental nucleus. The involvement of a number of
      these structures in a specific audiogenic stress responsive circuit is discussed.

PMID- 9283047
TI  - Facilitation or inhibition of the estradiol-induced gonadotropin surge in the
      immature rat by progesterone: regulation of GnRH and LH messenger RNAs and
      activation of GnRH neurons.
AB  - We have developed and extensively characterized immature female rat models to
      demonstrate inhibition or facilitation of the estradiol (E2)-induced gonadotropin
      surge by progesterone (P). We show here that the surge of free alpha-subunit is
      regulated similarly by P in these models. To investigate the possibility that P
      alters the biosynthesis of GnRH and/or LH, we measured levels of LH subunit mRNAs
      by Northern blot hybridization and GnRH mRNA by a solution hybridization-RNase
      protection assay. In the P inhibition model, alpha-subunit mRNA was significantly
      decreased when P was administered together with E2 for 32 or 48 h, and LHbeta, at
      29 h. In the facilitation model, neither alpha-subunit nor LHbeta mRNA increased
      with premature and enhanced release of LH and free alpha-subunit. Levels of GnRH
      mRNA in E2-treated rats were significantly higher on the afternoon of the LH
      surge than on that or the following morning. There was no effect of P on GnRH
      mRNA levels, however, before, during, or after the LH surge in either paradigm.
      The time course of activation of GnRH neurons in P-facilitated rats was
      determined by double-label immunocytochemistry for GnRH and cFos. When serum LH
      concentrations were basal there was no expression of cFos in GnRH neurons. LH
      secretion in P-facilitated rats was initiated at 14.00 h and remained elevated
      until at least 19.00 h. During this time 63-78% of GnRH neurons were cFos
      positive. Both serum LH concentrations and the percentage of cFos-activated GnRH
      neurons were significantly lower in control rats treated with E2 alone than in
      those treated also with P. IN CONCLUSION: 1) suppression of LH and free alpha
      subunit secretion by P can be accounted for at least partly by suppression of
      alpha-subunit mRNA levels; 2) P facilitation is not associated with changes in LH
      subunit or GnRH mRNA levels; 3) the large proportion of cFos-positive GnRH
      neurons in P-facilitated rats closely parallels increases in serum LH
      concentrations but is not accompanied by changes in GnRH mRNA levels. It is
      likely, therefore, that P acts in the facilitation model to trigger release of
      pre-existing GnRH stores by altering synthesis or activity of neuro
      transmitters/neuropeptides involved in GnRH regulation and/or release of LH
      stores by altering, for example, pituitary responsiveness to GnRH (including self
      priming) and components of the LH secretory apparatus. Similar possibilities may
      also obtain for the blockade of the gonadotropin surge in the inhibition model.

PMID- 9283048
TI  - Dopamine-beta-hydroxylase activity is necessary for hypothalamo-pituitary-adrenal
      (HPA) responses to ether, and stress-induced facilitation of subsequent HPA
      responses to acute ether emerges as HPA responses are inhibited by increasing
      corticosterone (B).
AB  - To determine a role of norepinephrine (NE) in stress-induced HPA function, young
      male rats were treated with diethyldithiocarbamide (DDC) which inhibits dopamine
      beta-hydroxylase, the enzyme that synthesizes NE from dopamine (DA). DDC injected
      5 h prior to ether stress stimulated ACTH and corticosterone (B) during this
      time, and there was no further HPA response to ether. To control for elevated B
      feedback in DDC effects on HPA responses to ether, rats were adrenalectomized
      (Adx) and replaced with no (0% B), moderate (40% B) and high (80% B) levels of
      steroid 5 d prior to DDC or saline with ether stress 5 h later; Sham-Adx rats
      were included. In Adx rats increasing B inhibited thymus weight, median eminence
      CRF content, pituitary and plasma ACTH. In saline-treated rats, ether 5 h later
      caused increased CRF content and plasma ACTH in Sham-Adx and Adx, 0% B, increased
      ACTH in Adx, 40% B, and no response in Adx, 80% B. B treatment did not alter
      catecholamine content, and DDC treatment reduced NE content in the
      paraventricular nuclei by 50-60% in all groups. 5 h after DDC, pituitary ACTH was
      decreased in all rats with B and plasma ACTH was increased in sham-Adx and Adx,
      40% B; thus DDC caused significant, prolonged stress which should facilitate
      subsequent HPA responses to acute stress. There was no HPA response to ether in
      Sham-Adx, Adx, 0% or 40% B groups, but there was a marked ACTH response to ether
      in the Adx, 80% B group treated with DDC. We conclude that: 1) the HPA response
      to ether stress is probably mediated by catecholamines; 2) DDC does not stimulate
      responses in the HPA axis in the absence of B; and, 3) facilitation of HPA
      responses to acute stress depends on increased steady-state B signals.
      Facilitated responses are probably not mediated by catecholamines. The
      consequence of facilitation is that under conditions of chronic stress and
      elevated B concentrations, as in depression or anorexia nervosa in man, or
      adjuvent-induced arthritis in rats, the HPA axis is continually responsive to new
      stimuli.

PMID- 9283049
TI  - Progesterone receptor participates in the stimulatory effect of LHRH,
      prostaglandin E2, and cyclic AMP on lordosis and proceptive behaviours in rats.
AB  - We explored the effect of the antiprogestin RU486 on the estrous behaviour
      (lordosis and proceptivity) induced in sexually experienced ovariectomized
      oestrogen primed rats by: 5 microg luteinizing hormone-releasing hormone (LHRH),
      100 microg prostaglandin E2 (PGE2), or 2 mg dibutyryl cyclic AMP (db cAMP).
      Pretreatment with 5 mg RU 486 (but not with vehicle) 60 min before the injection
      of the above-mentioned agents significantly decreased both lordosis and
      proceptive behaviours normally induced by such agents. Results suggest that the
      estrus-inducing action of LHRH, PGE2 and db cAMP occurs through the activation of
      the progesterone receptor.

PMID- 9283051
TI  - Effect of POMC(1-76), its C-terminal fragment gamma3-MSH and anti-POMC(1-76)
      antibodies on DNA replication in lactotrophs in aggregate cell cultures of
      immature rat pituitary.
AB  - Treatment of aggregate cell cultures of 14-day-old rat pituitary for 40 h with
      purified human (h) POMC(1-76) dose-dependently augmented the number of DNA
      replicating lactotrophs as estimated by autoradiography of [3H]-thymidine (3H-T)
      incorporation in cells immunostained for prolactin (PRL). No such effect was seen
      on the total number of 3H-T labelled cells (the majority of which did not contain
      any pituitary hormone in a detectable amount) or on the total number of
      lactotrophs. The effect of hPOMC(1-76) on 3H-T incorporation in lactotrophs was
      blocked by concomitant treatment with anti-hPOMC(1-76) monoclonal and polyclonal
      antibodies cross-reactive with rat POMC(1-74). The latter anti-hPOMC(1-76)
      antibodies also decreased the number of 3H-T incorporating lactotrophs in the
      absence of hPOMC(1-76). Gamma3-MSH, which is the C-terminal domain of hPOMC(1
      76), mimicked the effect of hPOMC(1-76) on 3H-T incorporation in lactotrophs but
      its potency was lower than that of hPOMC(1-76). Other melanocortin (MC) peptides
      such as alpha- and beta-MSH were also effective but were less potent than gamma3
      MSH. The difference in potency was not due to partial degradation of the
      peptides. hPOMC(1-76) did not affect 3H-T incorporation in other pituitary cell
      types. In contrast gamma3-MSH also augmented the number of 3H-T labelled
      somatotrophs and thyrotrophs. In the embryonic kidney 293 cell line stably
      transfected with the MC-3 receptor, gamma3-MSH (10 nM) augmented cAMP formation
      up to 30 times. In contrast, hPOMC(1-76) (100 nM) was inactive in this test
      system, indicating this peptide is not an agonist at the MC-3 receptor. The
      present investigation further supports the role of rat POMC(1-74) as a paracrine
      growth factor in the development of lactotrophs. The active core of POMC(1-76)
      does not seem to be restricted to its C-terminal domain gamma3-MSH as the latter
      peptide displays a growth promoting effect that is different from that of POMC(1
      76): it is less potent, it is not specific for lactotrophs and whereas the effect
      of gamma3-MSH may be mediated by the MC-3 receptor that of POMC(1-76) is not.

PMID- 9283050
TI  - Growth hormone-releasing hormone (GHRH)-GH-somatic growth and luteinizing hormone
      (LH)RH-LH-ovarian axes in adult female transgenic mice expressing human GH gene.
AB  - We have examined alterations in the hypothalamo-pituitary GH-somatic growth axis
      and the hypothalamo-pituitary LH-ovarian axis in a line of transgenic ICR mice
      expressing human GH (hGH) under the influence of the whey acid protein promoter.
      Transgenic female mice weighed twice as much as control females and were
      infertile. The size of the anterior pituitary (AP) was 1/3 that of the controls.
      In transgenic mice, acinar cells in the mammary and mandibular glands displayed
      hGH-immunoreactivity, and plasma hGH was detected by radioimmunoassay. In the
      medial basal hypothalamus (MBH) of transgenic females, the immunoreactive-GHRH
      level was decreased (P<0.01). There was a corresponding reduction in the number
      of GHRH-immunoreactive neurons in the arcuate nucleus (ARC) and in the
      immunostaining of GHRH nerve terminals in the median eminence. The level of
      somatostatin (SRIH) in the MBH was increased (P<0.05), and SRIH-immunoreactive
      neurons in the periventricular nucleus (PeV) were increased in size and number in
      transgenic mice. The MBH level of LHRH in transgenic animals was greater (P<0.01)
      than in controls, although there was no apparent difference in the number of LHRH
      immunoreactive neurons or in LHRH level in the preoptic area. There are fewer
      SRIH- and LHRH-immunoreactive neurons in the ARC in transgenic mice. Cells in the
      AP for GH, PRL, and LH were fewer in transgenic mice. The ovary suffered
      disturbance of follicular development and of corpora lutea formation. These
      results demonstrate that chronic overproduction of hGH may profoundly affect the
      organization of the GHRH/SRIH-GH-somatic growth axis and the LHRH-LH-ovarian axis
      due to reduction of GHRH-, SRIH- and LHRH-neurons in the ARC and increase of SRIH
      neurons in the PeV.

PMID- 9283052
TI  - Melatonin receptors in the brain and pituitary gland of hypothalamo-pituitary
      disconnected Soay rams.
AB  - In Soay rams in which the pituitary gland has been surgically separated from the
      hypothalamus, blood prolactin concentrations vary in response to changes in
      photoperiod and the administration of melatonin, as in intact animals, providing
      evidence that melatonin acts within the pituitary gland to control prolactin
      secretion. In this study the presence of potentially functional melatonin
      receptors in the pars tuberalis and zona tuberalis (PT/ZT) of hypothalamo
      pituitary disconnected (HPD) Soay rams is confirmed using both in vitro
      autoradiography with the ligand 2-(125I)-iodomelatonin and in situ hybridization
      for the melatonin receptor. There was no effect of the HPD operation on the
      pattern and quantity of 2-(125I)iodomelatonin binding in the brain demonstrating
      that this binding is independent of hypothalamic regulation. The possibility that
      melatonin may control prolactin secretion directly via specific receptors on
      lactotrophs was investigated using dual in situ hybridization with a (35S)
      labelled probe for the ovine melatonin receptor (Mel 1a(b)) and a Digoxigenin
      labelled probe for ovine prolactin. Melatonin receptor gene expression was
      observed in the PT/ZT in both intact and HPD rams, however, there was no
      colocalization with prolactin gene expression; only in the ZT was there a close
      association between cells expressing the melatonin receptor and lactotrophs. The
      results provide strong support for the view that melatonin acts via the PT/ZT to
      mediate the effects of photoperiod on the seasonal cycle in prolactin secretion.

PMID- 9283053
TI  - Can we treat hypertensive menopausal women with hormone replacement therapy?

PMID- 9283054
TI  - Taking the V out of genes V environment.

PMID- 9283055
TI  - The effect of hormone replacement therapy on blood pressure and cardiovascular
      risk factors in menopausal women with moderate hypertension.
AB  - OBJECTIVE: To assess the effect of injectable hormone replacement therapy (HRT)
      vs a placebo in hypertensive menopausal women. DESIGN AND METHODS: Prospective
      randomised double-blind study over 90 days. Fifty-five menopausal women with mild
      to moderate hypertension, stopped their antihypertensive medication and were
      studied for 2 weeks. Diastolic BP increased to over 105 mm Hg in five patients
      who were not included in the study. The remaining patients were randomly
      allocated to three groups: placebo (PL), estradiol valeranate 10 mg (E), and
      estradiol valeranate 4 mg plus prasterone enantate 200 mg (E+P). A further five
      patients were excluded from the study for different reasons. RESULTS: Standing
      and recumbent BP decreased in the PL group but did not change in the E and E+P
      patients. No change was observed in the serum levels of total cholesterol or low
      density lipoprotein (LDL)-cholesterol at the end of the trial. Plasma renin
      activity (PRA), aldosterone and insulin levels decreased during the study; PRA
      fell more significantly in the E+P group, the aldosterone reduction was highly
      significant in both hormone treated groups, specially the E+P group. Plasma
      insulin decreased in all groups and FSH levels were lower in the two treatment
      groups. CONCLUSIONS: In a randomised controlled trial no rise in BP was found
      after 90 days in hypertensive women with two forms of HRT. There was an
      unexpected fall in BP in those women allocated to placebo injections.

PMID- 9283056
TI  - A survey of clinician attitudes and management practices in hypertension.
AB  - In order to determine the compliance of Canadian physicians with evidence-based
      hypertension guidelines, a self-administered questionnaire survey was distributed
      to a stratified random sample of 473 physicians in Central Alberta, Canada in
      December 1995. Excluding non-deliverable questionnaires, a response rate of 67%
      was obtained. Twenty-five per cent of respondents routinely used the fourth
      Korotkoff sound to define diastolic blood pressure (DBP). Investigations
      recommended for the initial workup of a patient with mild hypertension included
      serum creatinine (90%), electrolytes (72%), glucose (50%), cholesterol (44%),
      electrocardiogram (65%), and urinalysis (76%). The non-pharmacologic treatment
      advice routinely advocated for patients with mild hypertension included salt
      restriction (87%), weight loss (100%), and regular aerobic exercise (92%). While
      46% of respondents recommended antihypertensive therapy for an otherwise healthy
      patient with an average DBP of 95 mm Hg, 76% recommended therapy for patients
      with the same BP plus target organ damage or other cardiovascular risk factors.
      Medication choices varied, although angiotensin-converting enzyme inhibitors were
      chosen by 46% for patients with uncomplicated essential hypertension and 67% for
      patients with other cardiovascular risk factors, and beta-blockers were the most
      frequently chosen first-line agents (56%) for the patient with target organ
      damage. There was considerable variability in the self-reported practice
      patterns, and concordance was greater for those recommendations which were
      consistent across the currently available guidelines. Consistent with the
      principle underlying all of the current hypertension guidelines, respondents were
      more aggressive in their treatment of hypertensive patients with other
      cardiovascular risk factors or target organ damage.

PMID- 9283057
TI  - Electrolytes are associated with blood pressure at old age: the Rotterdam Study.
AB  - We examined the association of urinary sodium and potassium excretion with blood
      pressure (BP) in the Rotterdam Study, a population-based study among 7983 men and
      women aged 55 and over. The present analysis included 1006 subjects with complete
      BP and urinary data who did not use antihypertensive drugs and did not report
      themselves to be hypertensive. Electrolyte excretions were assessed in a timed
      nocturnal urine sample and standardized to 24-h values. The association of
      electrolyte excretions with BP was studied in a multiple linear regression model
      with adjustment for age, sex, and body mass index. When sodium and potassium were
      entered simultaneously into the multivariate model, a 100 mmol increase in
      potassium was associated with a 9.4 decrease in systolic (P = 0.01) and a 4.9 mm
      Hg decrease in diastolic BP (P = 0.01). Sodium was directly related to BP, with a
      2.2 mm Hg increase in systolic (P = 0.06) and a 0.8 mm Hg increase in diastolic
      BP (P = 0.14) per 100 mmol. Our findings suggest that an increased intake of
      potassium and a decrease intake of salt may lower BP at old age.

PMID- 9283058
TI  - Blood pressure pattern in urban and rural areas in Isfahan, Iran.
AB  - Hypertension is a serious public health problem in many societies due to its high
      prevalence and the associated increases in the risks of cardiovascular and renal
      disease. Some epidemiologic surveys on hypertension in eastern Mediterranean
      countries have reported prevalence rates among adults of up to 30%, in urban
      areas. To investigate the effects of an urban vs a rural environment on blood
      pressure (BP), this population-based survey was carried out in the city of
      Isfahan and its surrounding villages in Iran. The study sample comprised 8639 men
      and women aged 19-70 years obtained by random cluster sampling. A questionnaire
      was completed and BP was measured three times for each individual by trained
      medical interns using standard methods. Results show significant differences
      between mean systolic and diastolic BP and the prevalence of hypertension among
      urban and rural populations (P < 0.001). BP increased significantly with
      increasing age in both populations (P < 0.001). Total prevalence of hypertension
      (BP > or =160/95 mmHg or using antihypertensive drugs) was 21% for urban
      populations and 7% for rural ones. Urban women had higher and rural women had a
      lower prevalence of hypertension compared to urban and rural men, respectively (P
      < 0.001). Diabetes and hypercholesterolemia were more prevalent among urban
      people (P < 0.001) but no significant difference in relation to smoking among the
      two populations was found (P > 0.05). Although these differences were not
      adjusted for body mass index (BMI), dietary habits and other factors, it seems
      that environmental factors are important determinants of BP, so a change in
      lifestyle may be effective in lowering BP among urban people.

PMID- 9283060
TI  - Race specific altitude effects on blood pressure.
AB  - Altitude affects blood pressure (BP) depending on duration and absolute altitude
      of exposure. Until now changes in BP during exposure to altitude were studied
      only in Caucasians. It is not known whether BP is affected differently in black
      and white people in response to altitude. During a 6-day climb on Kilimanjaro, BP
      was measured in five white and four black people. All participants (mean +/-
      s.d.: age 31 +/- 8 years, body mass index 22 +/- 2 kg/m2, BP 125 +/- 11/84 +/- 9
      mm Hg) had previous similar experience of high-altitude mountaineering. In the
      base camp (3040 m) systolic BP (SBP) was similar in both groups (131 +/- 9 vs 119
      +/- 8 mm Hg). During ascent until 4600 m SBP increased in all whites (6.5 +/- 2.2
      mm Hg) and decreased in all blacks (-7.3 +/- 4.6 mm Hg; P = 0.02, blacks vs
      whites). During descent SBP returned to initial values in whites, whereas it
      decreased further in blacks. Diastolic BP (DBP) and heart rate remained constant
      in all participants. During ascent body weight increased in all whites (1.0 +/-
      0.8 kg) and decreased in all blacks (-1.9 +/- 1.4 kg; P = 0.02, blacks vs whites)
      whereas it returned approximately to initial levels during descent: +0.8 +/- 0.4
      kg in blacks and -1.0 +/- 1.3 kg in whites (P = 0.03, blacks vs whites). In this
      study changes in SBP and body weight during exposure to high altitudes varied
      between whites and blacks. Fluid balance, acclimatisation, physical fitness or
      genetics could explain these findings.

PMID- 9283059
TI  - Lack of association between copper, zinc, selenium and blood pressure among
      healthy children.
AB  - Contradictory results have been published about the relation between copper, zinc
      and selenium and blood pressure (BP). To evaluate the role of these trace
      elements in BP regulation, we analysed the correlations between BP and copper,
      zinc and selenium, measured from serum, diet and hair among 3596 healthy children
      in a 6-year follow up. Fasting blood samples were used in serum copper, zinc and
      selenium analyses. The dietary intake of trace elements and energy were
      determined by the 48-h recall method. The hair copper and zinc analyses were
      performed from the naturally coloured hair samples. Correlation analysis was used
      to show the relation between BP and copper, zinc or selenium in each study year
      and during a 3- or 6-year follow-up period. The zinc-to-copper ratio in serum,
      diet and hair was calculated. In the correlation analyses the data was adjusted
      for weight and the daily intake of energy. Neither serum and diet copper or zinc,
      nor the zinc-to-copper ratio correlated uniformly with BP measured in the same
      year (correlation coefficients varying from -0.12 to 0.18) or in the subsequent
      years. Hair copper and zinc correlated weakly negatively with BP (correlation
      coefficients varying from -0.17 to -0.01). Serum selenium correlated weakly
      positively with systolic and diastolic BP measured in the same year (correlation
      coefficients varying from 0.03 to 0.14), but not with subsequent BP measured in
      the second or third survey. Dietary selenium had an inconsistent effect on BP
      (correlation coefficients varying from -0.14 to 0.26). In conclusion, copper,
      zinc, their ratio or selenium did not associate with BP, nor did they have any
      effect on subsequent BP.

PMID- 9283061
TI  - The influence of cuff size on blood pressure measurement.
AB  - The objective of the study was to determine the effect of the use of cuffs with
      different bladder sizes on the outcome of blood pressure (BP) measurements. Two
      sizes of bladders previously in common use in the study location (13 x 23 cm and
      16 x 23 cm) were compared with the current size (13 x 36 cm). A fully randomised,
      experimental study was carried out on a study population comprising 130 subjects
      (61 men, 69 women, aged between 22 and 70, mean 49) who were not undergoing
      special treatment for cardiovascular disease or hypertension at that time. The
      mean arm circumference was 32.9 cm (range 25-40 cm). BP measurements were carried
      out by one person, using a Hawksley random zero sphygmomanometer under
      standardised conditions. With the smallest bladder (13 x 23 cm) the highest
      systolic and diastolic BP was measured (mean SBP 127.2 mean DBP 77.0 mm Hg),
      followed by the bladder of 13 x 36 cm (125.1 resp. 75.4 mm Hg). The lowest BP was
      measured with the bladder of 16 x 23 cm (123.7 resp. 74.4 mm Hg). Differences
      between bladders were significant for all arm circumferences. Over the entire
      range of arm circumferences in the present study there is a small systematic
      difference in the BP measurements taken by the various bladder sizes. For
      individual readings the difference is less marked, in comparison to other factors
      that can affect BP measurements. However, in longitudinal studies a systematic
      error in BP can occur when measurements are made with different bladders during
      the study.

PMID- 9283062
TI  - High plasma endothelin-1 levels in hypertensive patients with low-renin essential
      hypertension.
AB  - Endothelin-1 (ET-1) is a potent vasoconstrictor peptide derived from endothelial
      cells and may be important in the control of systemic blood pressure (BP) and
      local blood flow. Immunoreactive ET-1 plasma levels may be normal or elevated in
      human arterial hypertension, although the exact pathophysiological role of ET-1
      remains to be established. The aim of our study was to determine the relationship
      between the components of the renin-angiotensin-aldosterone system and plasma ET
      1 levels in patients with low, normal or high-renin essential hypertension. The
      study groups included 13 patients with low-renin essential hypertension (average
      age 43.5 +/- 16.2 years), 16 patients with normal-renin essential hypertension
      (46.5 +/- 13.4 years), 11 patients with high-renin essential hypertension (40.7
      +/- 13.8 years) and 12 healthy subjects (43.1 +/- 11.4 years). Our results
      demonstrated that the mean ET-1 values of all patients with essential
      hypertension were 10.4 +/- 3.4 pg/ml; there was not a statistical correlation
      between plasma renin activity (PRA) and the ET-1 levels of hypertensives; instead
      there was a statistically significant correlation between plasma ET-1 and plasma
      aldosterone (PA) (r = 0.393; P < 0.026). In particular mean plasma ET-1 values in
      patients with low-renin essential hypertension (12.6 +/- 2.1 pg/ml) were
      significantly higher (ANOVA = 0.000, P < 0.05) than those of normotensive
      subjects (7.7 +/- 1.7 pg/ml), patients with normal-renin essential hypertension
      (8.5 +/- 2.8 pg/ml), and patients with high-renin essential hypertension (9.9 +/-
      3.8 pg/ml), respectively. There was a statistical correlation between PA and ET-1
      levels in patients with low-renin essential hypertension (r = 0.619, P < 0.024).
      Our study demonstrated that there was an increase of circulating ET-1 levels in
      patients with low-renin essential hypertension and ET-1 plasma levels correlated
      with PA. The results suggest that ET-1 may play an important role in this
      particular form of human essential hypertension.

PMID- 9283063
TI  - Platelet sodium/hydrogen ion exchange in normal pregnancy and non-proteinuric pre
      eclampsia.
AB  - In non-pregnant individuals, abnormalities in cation transport in vascular
      tissues have been linked to essential hypertension. In the present study, we
      consider whether Na+/H+ exchange (NHE) is affected in non-proteinuric pre
      eclampsia (NPP). Platelet NHE characteristics and plasma cholesterol were
      measured in a cross-sectional study of normal primigravidae at 14 +/- 0.5 (n =
      9), 29 +/- 0.7 (n = 7), 39 +/- 0.4 (n = 8) weeks gestation, in women with NPP (n
      = 15) and in non-pregnant women (n = 8). Amiloride-sensitive 22Na uptake was
      measured in platelets which had been acid loaded, to stimulate NHE, by suspension
      in isotonic potassium propionate buffer (pH 6.7). Intraplatelet radioactivity was
      used to calculate the affinity (Km) and the capacity (Vmax) of Na+ uptake. In
      normotensive women, Vmax (mean +/- s.e.) at 14, 29, 39 weeks gestation and 6
      weeks postpartum were 452 +/- 46, 469 +/- 33, 713 +/- 101 and 562 +/- 77
      pmolNa+/10(6) cells/min respectively; the third trimester values were higher (P <
      0.05) than those in the first and second trimester and were also higher than
      those of non-pregnant women (415 +/- 20). Vmax of patients with NPP in the third
      trimester (712 +/- 44) was not different from gestational age-matched controls.
      Km values were not affected by gestational age or NPP. Plasma cholesterol
      concentration was positively correlated with Vmax values during normotensive
      pregnancy (r = 0.493, P < 0.05). In conclusion, the capacity for amiloride
      sensitive Na+ uptake by platelets correlates positively with gestational age
      during normal pregnancy. However, neither the capacity nor affinity for Na+ was
      altered in NPP platelets suggesting that NHE is not implicated in the
      pathophysiology of this condition.

PMID- 9283065
TI  - Ambiguities in angiotensin-converting enzyme allele genotyping: a comparison of
      three methods.

PMID- 9283064
TI  - The addition of mibefradil to chronic hydrochlorothiazide therapy in hypertensive
      patients is associated with a significant antihypertensive effect.
AB  - OBJECTIVE: To evaluate the antihypertensive efficacy, tolerability, safety, and
      dose-response characteristics of the novel calcium antagonist, mibefradil, in
      combination with a diuretic regimen. DESIGN: A multinational, double-blind,
      randomised, placebo-controlled, parallel-design trial. METHODS: Three hundred and
      seven patients whose mild-to-moderate essential hypertension remained
      uncontrolled after 4 weeks of treatment with hydrochlorothiazide (HCTZ) 25 mg/day
      and placebo were randomised to receive combined treatment with HCTZ and once
      daily doses of 12.5, 25, 50, or 100 mg of mibefradil or placebo. After 8 weeks of
      combined treatment, HCTZ was withdrawn and the mibefradil groups continued on
      their respective doses for an additional 6 weeks. RESULTS: After 8 weeks, the
      addition of once-daily doses of mibefradil to the initial HCTZ regimen resulted
      in clinically relevant, dose-related reductions in sitting diastolic blood
      pressure (SDBP) and sitting systolic blood pressure (SSBP) at trough, which were
      significantly greater in the 50 and 100 mg dose groups compared to the placebo
      group (P < or = 0.003). Placebo-corrected treatment effects on SDBP and SSBP at
      the end of the combined treatment period relative to baseline were, respectively,
      -4.1 and -8.0 mm Hg in the 50 mg mibefradil group and -9.5 and -8.0 mm Hg in the
      100 mg mibefradil group. Therapeutic response rates to combination mibefradil and
      HCTZ therapy were high and dose related, reaching 82% for SDBP in the 100 mg
      group. CONCLUSIONS: The addition of once-daily doses of 50 or 100 mg of
      mibefradil to patients whose hypertension is not controlled by HCTZ alone is well
      tolerated and effective in improving BP control.

PMID- 9283073
TI  - Mapping conformational changes in a protein: application of a protein
      footprinting technique to cAMP-induced conformational changes in cAMP receptor
      protein.
AB  - We have used protein footprinting [Heyduk, E., & Heyduk, T. (1994) Biochemistry
      33, 9643] to detect and map ligand-induced conformational changes in cAMP
      receptor protein (CRP). The binding of cAMP to CRP dramatically increases the
      specific DNA binding activity of the protein and, as has been previously shown,
      induces conformational changes in the protein. Protein footprinting experiments
      with the free CRP, the CRP-cAMP complex, and the CRP-cGMP complex were analyzed
      quantitatively. Binding of cAMP produced measurable differences in the
      susceptibility of CRP to the cleavage by Fe-EDTA. Almost all of these changes
      occurred in the C-terminal domain (DNA binding domain) of the protein. Additional
      changes were observed at the ends of the C alpha-helix, which is involved in
      intersubunit contacts in the CRP dimer, and in the hinge peptide, connecting N
      terminal and C-terminal domains of the protein. The boundaries of the regions in
      the C-terminal domain, which exhibited changes in susceptibility to Fe-EDTA
      cleavage, almost exactly corresponded to D, E, and F alpha-helices which are
      involved directly in the recognition of DNA. The F alpha-helix, which provides
      all base-specific contacts in the CRP-DNA complex, became hypersensitive to Fe
      EDTA-mediated cleavage, whereas the solvent exposure of D and E alpha-helices was
      decreased upon binding of cAMP. These results suggest that a significant part of
      cAMP-induced conformational change in CRP involves a movement of secondary
      structure elements in the C-terminal domain of the protein so that the
      recognition F alpha-helix becomes exposed to the solvent. In contrast to cAMP,
      binding of cGMP produced insignificant changes in susceptibility to Fe-EDTA
      mediated cleavage. This is consistent with the inability of cGMP to induce
      functional conformational changes in CRP. The protein footprinting technique
      appears to be sufficiently sensitive for detection and mapping of ligand-induced
      conformational changes in proteins.

PMID- 9283074
TI  - Structure of the Aspergillus oryzae alpha-amylase complexed with the inhibitor
      acarbose at 2.0 A resolution.
AB  - The three-dimensional structure of the Aspergillus oryzae alpha-amylase (TAKA
      amylase), in complex with the inhibitor acarbose, has been determined by X-ray
      crystallography at a resolution of 1. 98 A. The tetrasaccharide inhibitor is
      present as a hexasaccharide presumably resulting from a transglycosylation event.
      The hexasaccharide occupies the -3 to +3 subsites of the enzyme, consistent with
      the known number of subsites determined by kinetic studies, with the acarbose
      unit itself in the -1 to +3 subsites of the enzyme. The transition state
      mimicking unsaturated pseudo-saccharide occupies the -1 subsite as expected and
      is present in a distorted 2H3 half-chair conformation. Careful refinement plus
      extremely well-resolved unbiased electron density suggest that the hexasaccharide
      represents a genuine transglycosylation product, but the possibility that this
      apparent species results from an overlapping network of tetrasaccharides is also
      discussed. Catalysis by alpha-amylase involves the hydrolysis of the alpha-1,4
      linkages in amylose with a net retention of the anomeric configuration, via a
      double-displacement mechanism, as originally outlined by Koshland [Koshland, D.
      E. (1953) Biol. Rev. 28, 416-336]. The enzymatic acid/base and nucleophile,
      residues Glu230 and Asp206, respectively, are appropriately positioned for
      catalysis in this complex, and the hexasaccharide species allows mapping of all
      the noncovalent interactions between protein and ligand through the enzyme's six
      subsites.

PMID- 9283075
TI  - Probing the non-proline cis peptide bond in beta-lactamase from Staphylococcus
      aureus PC1 by the replacement Asn136 --> Ala.
AB  - A non-proline cis peptide is present between Glu166 and Ile167 in the active site
      of beta-lactamase from Staphylococcus aureus PC1. To examine the role of the
      interaction between the side chain of Asn136 and the main chain of Glu166, the
      site-directed mutant N136A was produced. The enzyme shows no measurable
      hydrolytic activity toward a variety of penicillins or cephalosporins except for
      the chromogenic cephalosporin, nitrocefin. For nitrocefin, the progress curve
      exhibits a fast burst with a stoichiometry of 1 mol of degraded substrate per
      mole of enzyme followed by a slow phase with a hydrolysis rate that is reduced by
      approximately 700-fold compared with that of the wild-type enzyme. Thus, the
      mutant enzyme is deacylation defective. Monitoring the hydrolysis of nitrocefin
      after preincubation with a number of beta-lactam compounds shows that
      cephalosporins form stable acyl complexes with the enzyme, whereas penicillins do
      not. The molecular weight of the mutant was determined by electrospray mass
      spectrometry, and the presence of the stable acyl enzyme adducts with
      cephaloridine and cefotaxime was confirmed by both electrospray and MALDI mass
      spectrometry. Therefore, in addition to impairing deacylation, the acylation
      machinery has been altered compared with the wild-type enzyme to act on
      cephalosporins and not on penicillins. Urea denaturation and thermal unfolding
      studies show that the N136A mutant enzyme is less stable than the wild-type
      enzyme. However, stability against chemical denaturation of the mutant enzyme is
      enhanced in the presence of cephaloridine beyond the stability of the wild-type
      protein. This is attributed to accumulation of favorable interactions between the
      cephaloridine and the protein, which play a role in the folded state and not in
      the unfolded state.

PMID- 9283076
TI  - Identification of essential amino acids in phenylalanine ammonia-lyase by site
      directed mutagenesis.
AB  - The postulated precursor of the prosthetic dehydroalanine of phenylalanine
      ammonia-lyase (PAL), serine 202, was changed to cysteine by site-directed
      mutagenesis. After cloning and heterologous expression in Escherichia coli, the
      gene product was assayed for PAL activity. Mutant S202C showed full catalytic
      activity, and its kinetic constants and the amount of thiol groups were identical
      to those of wild-type PAL. It must be concluded that in a posttranslational
      modification both water and hydrogen sulfide can be eliminated from the amino
      acid in position 202 to form dehydroalanine. In an attempt to identify further
      amino acids essential either for the posttranslational modification or for
      catalysis, arginine 174, glutamine 425, and lysine 499 were changed to
      isoleucine. Analysis of the heterologously expressed mutated gene products
      revealed that only the R174I mutant showed a significantly lower Vmax value
      (1/450) identifying this arginine as important. This finding was supported by
      treatment of wild-type PAL and mutant R174I with phenylglyoxal and 2,3
      butandione. Both react specifically with the guanidino group of arginine. They
      irreversibly inhibited wild-type PAL but had no influence of the Vmax value of
      mutant R174I. Preincubation with l-phenylalanine protected wild-type PAL from
      inhibition by phenylglyoxal indicating that arginine 174 is close to the active
      site. Incubation with KCN irreversibly abolished the remaining activity of mutant
      R174I leading to the conclusion that arginine 174 is important in catalysis.

PMID- 9283078
TI  - Nonmediated flip-flop of anionic phospholipids and long-chain amphiphiles in the
      erythrocyte membrane depends on membrane potential.
AB  - The nonmediated inward translocation (flip) of the anionic fluorescent N-(7
      nitrobenz-2-oxa-1,3-diazol-4-yl)- (NBD-)labeled phospholipid phosphatidylmethanol
      (PM) from the outer to the inner membrane leaflet of human erythrocytes and vice
      versa depends on membrane potential. Interestingly, inside-positive potentials
      due to chloride gradients and the native chloride conductance of the cells
      resulted in an increase of the flip rates. This flip enhancement could be
      suppressed by addition of gramicidin D, which increases cation conductance, or
      4,4'-diisothiocyanatostilbene-2,2'-disufonate (DIDS), which inhibits anion
      conductance. Conversely, inside negative potentials established by an outward
      directed K+ gradient in the presence of gramicidin on DIDS-treated cells resulted
      in a decrease of flip rate. Flip rate exhibited an exponential dependence on
      membrane potential. The opposite effects of the positive and negative potentials
      were obtained for the outward translocation (flop) from the inner to the outer
      membrane leaflet. Similar potential dependencies were found for the nonmediated
      flip of anionic NBD-labeled phosphatidic acid (PA) and 2-(N
      decyl)aminonaphthalene-6-sulfonic acid (2,6-DENSA) following blockage of the band
      3-mediated component of flip. The membrane potential also influences the
      stationary distribution of the anionic lipids between the inner and outer
      leaflets. The distribution is shifted to the inner leaflet by increasingly
      positive potentials and to the outer leaflet by increasingly negative potentials.
      It is concluded that nonmediated flip-flop of the anionic phospholipids and the
      long-chain sulfonate represents electrogenic translocation of the unprotonated
      charged lipids across the hydrophobic barrier.

PMID- 9283077
TI  - Comparison of DNA bending by Fos-Jun and phased A tracts by multifactorial
      phasing analysis.
AB  - Studies of DNA bending by Fos and Jun using different methods have yielded
      contradictory results. Whereas gel electrophoretic phasing analysis indicates
      that Fos and Jun bend DNA, results obtained through X-ray crystallography and
      ligase-catalyzed cyclization suggest that they do not. To test the assumptions
      underlying phasing analysis and to examine DNA bending by Fos and Jun, a
      multifactorial phasing analysis approach based on the distinct electrophoretic
      mobilities of DNA fragments of diverse shapes was developed. In this approach,
      the spacing between the bends, the length of sequences flanking the bends, and
      the acrylamide concentration in the gel are varied. Two closely spaced intrinsic
      bends with long flanking sequences had the same effect on electrophoretic
      mobility as a single bend corresponding to the sum of the bends when they were
      arranged in phase, and the difference between the bends when they were arranged
      out of phase. Based on the phase-dependent electrophoretic mobility variation of
      fragments containing intrinsic DNA bends of different magnitudes, three criteria
      for determination whether the phase-dependent mobility variation of protein-DNA
      complexes is caused by DNA bending were adopted. Complexes formed by the bZIP
      domains of Fos and Jun fulfilled each of these criteria. First, the
      electrophoretic mobility variation induced by Fos and Jun was proportional to
      that caused by an intrinsic bend over a broad range of acrylamide concentrations.
      Second, the mobility difference between fragments containing in phase and out of
      phase bends was reduced by an increase in the separation between the bends. The
      separation between the bends had the same effect on the electrophoretic mobility
      variation caused by Fos and Jun as well as intrinsic bends on long DNA fragments
      at low acrylamide concentrations. Third, on short DNA fragments analyzed at high
      acrylamide concentrations, two intrinsic bends separated by long spacers caused a
      larger decrease in electrophoretic mobility when they were out of phase than when
      they were in phase. This reversal of the phase dependence of the electrophoretic
      mobility variation was also observed for complexes formed by truncated Fos and
      Jun. Thus, the phase-dependent mobility variation of Fos and Jun complexes is due
      to DNA bending.

PMID- 9283079
TI  - Site-directed mutations of the 4Fe-ferredoxin from the hyperthermophilic archaeon
      Pyrococcus furiosus: role of the cluster-coordinating aspartate in physiological
      electron transfer reactions.
AB  - Ferredoxin from the hyperthermophilic archaeon Pyrococcus furiosus is a monomeric
      protein (7.5 kDa) that contains a single [4Fe-4S]1+, 2+ cluster. The protein is
      unusual in that its cluster is coordinated by three Cys and one Asp residue,
      rather than by the typical four Cys residues. Site-directed mutagenesis has been
      used to obtain mutant forms in which the cluster-coordinating Asp was replaced by
      Cys (D14C) and also by Ser (D14S), together with a third mutant (A1K) which
      contained N-Met-Lys at the N-terminus instead of N-Ala. Analyses using UV-visible
      absorption, far-UV circular dichroism, and EPR spectroscopy showed that there
      were no gross structural differences between the native and the three mutant
      forms and that they each contained a [4Fe-4S] cluster. The reduction potentials,
      determined by direct electrochemistry (at 23 degrees C, pH 8.0), of the D14S,
      D14C, and A1K mutants were -490, -422, and -382 mV, respectively, which compare
      with values of -375 mV for native [4Fe-4S]-containing ferredoxin and -160 mV for
      the [3Fe-4S]-containing form. The native, D14C, and A1K proteins functioned as
      electron acceptors in vitroat 80 degrees C for pyruvate ferredoxin oxidoreductase
      (POR) and aldehyde ferredoxin oxidoreductase (AOR) from P. furiosus using
      pyruvate and crotonaldehyde as substrates, respectively. The calculated kcat/Km
      values were similar for the three proteins when ferredoxin reduction was measured
      either directly by visible absorption or indirectly by coupling ferredoxin
      reoxidation to the reduction of metronidazole. In contrast, using the D14S mutant
      and the 3Fe-form of the native ferredoxin as electron acceptors, the activity
      with AOR was virtually undetectable, and with POR the calculated kcat/Km values
      were at least 3-fold lower than those obtained with the native (4Fe-), D14C, and
      A1K proteins. The ability of this 4Fe-ferredoxin to accept electrons from two
      oxidoreductases of the same organism is therefore not absolutely dependent upon
      Asp14, as this residue can be effectively replaced by Cys. However, the
      efficiency of electron transfer is compromised if Asp14 is replaced by Ser, or if
      the 4Fe-cluster is converted to the 3Fe-form, but Asp14 does not appear to offer
      any kinetic advantage over the expected Cys.

PMID- 9283080
TI  - Peptidylglycine alpha-hydroxylating monooxygenase: active site residues,
      disulfide linkages, and a two-domain model of the catalytic core.
AB  - Peptidylglycine alpha-hydroxylating monooxygenase (PHM) is a copper, ascorbate,
      and molecular oxygen dependent enzyme that catalyzes the first step leading to
      the C-terminal amidation of glycine-extended peptides. The catalytic core of PHM
      (PHMcc), refined to residues 42-356 of the PHM protein, was expressed at high
      levels in CHO (DG44) (dhfr-) cells. PHMcc has 10 cysteine residues involved in 5
      disulfide linkages. Endoprotease Lys-C digestion of purified PHMcc under
      nonreducing conditions cleaved the protein at Lys219, indicating that the protein
      consists of separable N- and C-terminal domains with internal disulfide linkages,
      that are connected by an exposed linker region. Disulfide-linked peptides
      generated by sequential CNBr and pepsin treatment of radiolabeled PHMcc were
      separated by reverse phase HPLC and identified by Edman degradation. Three
      disulfide linkages occur in the N-terminal domain (Cys47-Cys186, Cys81-Cys126,
      and Cys114-Cys131), along with three of the His residues critical to catalytic
      activity (His107, His108, and His172). Two disulfide linkages (Cys227-Cys334 and
      Cys293-Cys315) occur in the C-terminal domain, along with the remaining two
      essential His residues (His242, His244) and Met314, thought to be essential in
      binding one of the two nonequivalent copper atoms. Substitution of Tyr79 or
      Tyr318 with Phe increased the Km of PHM for its peptidylglycine substrate without
      affecting the Vmax. Replacement of Glu313 with Asp increased the Km 8-fold and
      decreased the kcat 7-fold, again identifying this region of the C-terminal domain
      as critical to catalytic activity. Taking into account information on the copper
      ligands in PHM, we propose a two-domain model with a copper site in each domain
      that allows spatial proximity between previously described copper ligands and
      residues identified as catalytically important.

PMID- 9283081
TI  - Thermodynamics of metal ion binding and denaturation of a calcium binding protein
      from Entamoeba histolytica.
AB  - The thermodynamics of the binding of calcium and magnesium ions to a calcium
      binding protein from Entamoeba histolytica was investigated by isothermal
      titration calorimetry (ITC) in 20 mM MOPS buffer (pH 7.0) at 20 degrees C.
      Enthalpy titration curves of calcium show the presence of four Ca2+ binding
      sites. There exist two low-affinity sites for Ca2+, both of which are exothermic
      in nature and with positive cooperative interaction between them. Two other high
      affinity sites for Ca2+ exist of which one is endothermic and the other
      exothermic, again with positive cooperative interaction. The binding constants
      for Ca2+ at the four sites have been verified by a competitive binding assay,
      where CaBP competes with a chromophoric chelator 5,5'-Br2 BAPTA to bind Ca2+ and
      a Ca2+ titration employing intrinsic tyrosine fluorescence of the protein. The
      enthalpy of titration of magnesium in the absence of calcium is single site and
      endothermic in nature. In the case of the titrations performed using protein
      presaturated with magnesium, the amount of heat produced is altered. Further, the
      interaction between the high-affinity sites changes to negative cooperativity. No
      exchange of heat was observed throughout the addition of magnesium in the
      presence of 1 mM calcium. Titrations performed on a cleaved peptide comprising
      the N-terminus and the central linker show the existence of two Ca2+ specific
      sites. These results indicate that this CaBP has one high-affinity Ca-Mg site,
      one high-affinity Ca-specific site, and two low-affinity Ca-specific sites. The
      thermodynamic parameters of the binding of these metal ions were used to
      elucidate the energetics at the individual site(s) and the interactions involved
      therein at various concentrations of the denaturant, guanidine hydrochloride,
      ranging from 0.05 to 6.5 M. Unfolding of the protein was also monitored by
      titration calorimetry as a function of the concentration of the denaturant. These
      data show that at a GdnHCl concentration of 0.25 M the binding affinity for the
      Mg2+ ion is lost and there are only two sites which can bind to Ca2+, with
      substantial loss of cooperativity. At concentrations beyond 2.5 M GdnHCl, at
      which the unfolding of the tertiary structure of this protein is observed by near
      UV CD spectroscopy, the binding of Ca2+ ions is lost. We thus show that the
      domain containing the two low-affinity sites is the first to unfold in the
      presence of GdnHCl. Control experiments with change in ionic strength by addition
      of KCl in the range 0.25-1 M show the existence of four sites with altered ion
      binding parameters.

PMID- 9283082
TI  - Role of quaternary structure in the stability of dimeric proteins: the case of
      ascorbate oxidase.
AB  - Equilibrium denaturation experiments have been performed in order to study the
      dissociation into monomers and unfolding of the dimeric copper-containing enzyme
      ascorbate oxidase by urea and guanidine hydrochloride. The process has been
      followed by fluorescence intensity and anisotropy, by optical density, and by
      circular dichroism as a function of denaturant concentration. The noncoincidence
      of the unfolding curves obtained by different techniques suggests that a
      multiphasic process is occurring. The study of enzymatic activity and aromatic
      circular dichroism as a function of denaturant concentration shows that the first
      transition involves a change in the protein tertiary structure which is
      accompanied by the loss of biological function. Gel electrophoresis,
      ultracentrifugation, and protein dilution experiments demonstrate that a large
      fraction of protein molecules is still dimeric during this first transition with
      a stability which is strictly dependent on the denaturant used. The free energy
      change from the native form to this intermediate species was estimated to be
      approximately 3.5 kcal/mol. The binding of 1-anilino-8-naphthalenesulfonic acid
      to the partially unfolded, inactive ascorbate oxidase dimer also suggests a large
      conformational change accompanied by copper release, allowing the probe to
      penetrate deep inside the protein structure. Further denaturation to give a fully
      unfolded form is protein concentration dependent, suggesting that dissociation
      into monomers is occurring. The monomers appear to be very unstable. No evidence
      for structured intermediates was in fact detected in the last step of the
      denaturation process. A three-state model has been used to fit the fluorescence
      data, and the fractions of different species have been calculated as a function
      of denaturant concentration. The total free energy change of the unfolding
      transition using either urea or guanidine hydrochloride is rather small (
      approximately 15-16 kcal/mol) and quite comparable to the value found for smaller
      proteins. The loss of secondary structure which occurs in the second part of the
      unfolding transition may be described by a simple two-state process which is
      characterized by a free energy change of 12-13 kcal/mol. These results suggest
      that the folding process of ascorbate oxidase follows a hierarchical model
      (Jaenicke, 1991). In this context, the assembly of monomers in a dimeric molecule
      plays a fundamental role by enhancing the protein stability and driving the final
      organization of the tertiary structure.

PMID- 9283084
TI  - Deletion of amino acids 261-269 in the brown fat uncoupling protein converts the
      carrier into a pore.
AB  - The uncoupling protein (UCP) from brown adipose tissue mitochondria is a carrier
      that catalyzes proton re-entry into the matrix and thus dissipates the proton
      electrochemical potential gradient as heat. UCP activity is regulated: purine
      nucleotides inhibit while fatty acids activate transport. We have previously
      reported that sequence 261-269 of the UCP has a closely related counterpart in
      the adenine nucleotide translocator, as well as in the DNA binding domain of the
      estrogen receptor. Site-directed mutagenesis of the UCP showed that deletion of
      amino acids 267-269 in the UCP abolished nucleotide inhibition [Bouillaud, F., et
      al. (1994) EMBO J. 13, 1990-1997]. Complete deletion of the homologous domain
      (UCPDelta9) produced a highly deleterious mutant that collapsed the mitochondrial
      membrane potential and halted yeast growth. Since under our growth conditions
      revertants appeared rapidly, it was not possible to characterize this mutant. In
      this article, we have designed conditions to isolate mitochondria containing
      significant amounts of the UCPDelta9 mutant protein. These mitochondria show no
      respiratory control and are insensitive to nucleotides. Investigation of the
      permeability properties revealed that UCPDelta9 mitochondria swell rapidly in
      potassium salts in the absence of valinomycin, thus indicating a loss of
      specificity. The size exclusion properties of this mutant were determined with
      polyethylene glycols of various molecular masses (400-20000 Da), and it was found
      that UCPDelta9 can catalyze permeation of molecules of up to 1000 Da. We conclude
      that the deletion of amino acids 261-269 converts the UCP into an unspecific
      pore.

PMID- 9283083
TI  - Helix propensities are identical in proteins and peptides.
AB  - Our understanding of the factors stabilizing alpha-helical structure has been
      greatly enhanced by the study of model alpha-helical peptides. However, the
      relationship of these results to the folding of helices in intact proteins is not
      well characterized. Helix propensities measured in model peptides are not in good
      agreement with those from proteins. In order to address these questions, we have
      measured helix propensities in the alpha-helix of ribonuclease T1 and a helical
      peptide of identical sequence. We have previously demonstrated excellent
      agreement between peptide and protein for the nonpolar amino acids [Myers, J. K.,
      Pace, C. N., and Scholtz, J. M. (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 2833
      2837]. Most other amino acids also show good agreement, although certain polar
      amino acids are exceptions. Helix propensities measured in the ribonuclease T1
      peptide/protein are compared with those measured in other systems. Reasonable
      agreement is found between most systems; however, our propensities differ
      substantially from those measured in several model peptide systems. Alanine-based
      peptides overestimate the propensity differences by a factor of 2, and host/guest
      experiments underestimate them by a factor of 2-3.

PMID- 9283085
TI  - Oligomycin sensitivity conferring protein (OSCP) of bovine heart mitochondrial
      ATP synthase: high-affinity OSCP-Fo interactions require a local alpha-helix at
      the C-terminal end of the subunit.
AB  - Earlier studies on oligomycin sensitivity conferring protein (OSCP) of bovine
      mitochondrial ATP synthase (F1Fo) indicated that a deletion mutant form (CD-10),
      lacking the last 10 amino acid residues (K181-L190), was unable to bind to the Fo
      segment, or reconstitute energy-linked reactions in OSCP-depleted F1Fo complexes
      [Joshi et al. (1996) Biochemistry 35, 12094-12103]. So far as known, the K181
      L190 region of all mammalian species of OSCP harbors four charged residues at
      positions 181, 184, 187, and 188, while secondary structure predictions suggest
      that the K178-M186 region has a high propensity to form a helix [Ovchinnikov et
      al. (1984) FEBS Lett. 166, 19-22; Higuti et al. (1993) Biochim. Biophys. Acta
      1172, 311-314; Grinkevich et al. ( 1994) Biol. Membr. 11, 310-323; Engelbrecht et
      al. (1991) Z. Naturforsch., C: Biochem., Biophys., Biol.,Virol. 46, 759-764].
      Present studies were undertaken to clarify the role of individual amino acids in
      the K181-L190 region in OSCP-stimulated energy coupling. Our data show that
      simultaneous replacements of all four charged residues by uncharged but polar
      glutamines, or of K181-R184 by apolar alanines, had no significant influence
      either on the total alpha-helix content of the mutant forms or on the ability of
      mutant OSCPs to couple energy-linked reactions. However, a substitution of the
      K181-M186 region by six proline residues led to complete loss in the coupling
      activity of the resultant mutant. A detailed analysis of the 6-proline mutant
      form revealed that the variant was indistinguishable from WT OSCP with respect to
      expression characteristics, affinity for S-Sepharose, and ability to interact
      with F1, but was unable to complex with the Fo segment. These studies suggest
      that the global protein structure was not destabilized. The helix potential
      prediction analyses showed that the 6-proline OSCP displayed a marked decrease in
      the helix-forming propensity in the region corresponding to residues 175-190.
      Quantitative CD analyses to measure helical content demonstrated that both of the
      mutant forms 6-proline-OSCP and CD-10 had a somewhat lower alpha-helical content
      compared to WT protein, while synthetic peptides corresponding in sequence to the
      K178-L190 region displayed a high propensity to form a helix. Taken together,
      these results suggest that the C-terminal end of OSCP encompasses an alpha-helix
      which is crucial for high-affinity interactions of the C-terminal end of this
      subunit with Fo in the F1Fo enzyme.

PMID- 9283086
TI  - On the origin of sphingolipid/cholesterol-rich detergent-insoluble cell
      membranes: physiological concentrations of cholesterol and sphingolipid induce
      formation of a detergent-insoluble, liquid-ordered lipid phase in model
      membranes.
AB  - Detergent-insoluble membrane fragments that are rich in sphingolipid and
      cholesterol can be isolated from both cell lysates and model membranes. We have
      proposed that these arise from membranes that are in the liquid-ordered phase
      both in vivo and in vitro [Schroeder et al. (1994) Proc. Natl. Acad. Sci. U.S.A.
      91, 12130-12134]. In order to detect formation of the liquid-ordered phase while
      avoiding possible detergent artifacts, we have now used fluorescence quenching to
      examine the phase behavior of mixtures of phosphatidylcholines, sphingolipids,
      and cholesterol. Phase separation was found in binary mixtures of either
      dipalmitoylphosphatidylcholine (DPPC) or sphingomyelin (SM) and a nitroxide
      labeled phosphatidylcholine (12SLPC). A DPPC- or SM-enriched solidlike gel phase
      coexisted with a 12SLPC-enriched liquid-disordered fluid phase at 23 degrees C.
      As expected, phase separation was not seen at low concentrations of DPPC or SM.
      Instead, only a uniform fluid phase was present. Including 33 mol % cholesterol
      in model membranes greatly promoted phase separation. Phase separation was seen
      at higher temperatures and/or at lower concentrations of DPPC or SM in the
      presence of cholesterol than in its absence. Mixtures of DPPC or SM and
      cholesterol are known to form the liquid-ordered phase. Therefore, the fact that
      phase separation was observed in the cholesterol-containing membranes shows that
      liquid-ordered and liquid-disordered phase domains coexist. At 37 degrees C, the
      SM-enriched liquid-ordered phase was first seen at a SM/PC ratio of close to
      0.25, when SM made up 17% of the total lipid including cholesterol. (This is
      similar to or less than the SM concentration of the plasma membranes of mammalian
      cells.) Furthermore, the detergent insolubility of cholesterol-containing model
      membranes correlated well with the amount of liquid-ordered phase as detected by
      fluorescence quenching. Thus, the detergent-insoluble membranes isolated from
      cells are likely to exist in the liquid-ordered phase prior to detergent
      extraction. The promotion of liquid-ordered phase formation may be an important
      function of cholesterol and sphingolipids in cells and may be a major distinction
      between the cholesterol- and sphingolipid-rich plasma membrane and most other
      cellular membranes.

PMID- 9283087
TI  - Binding characterization of a putative cGMP transporter in the cell membrane of
      human erythrocytes.
AB  - Cyclic GMP is an intracellular signal molecule whose biological and
      pharmacological role is not well understood. Recent studies with human
      erythrocytes and other cell types (normal and transformed) have shown that the
      extrusion of cGMP is an ATP-dependent and saturable process. In this paper, we
      present our studies on binding of [3H]-cGMP to human erythrocyte ghost and its
      solubilized extracts. At 4 degrees C, an apparent dissociation constant of 0.15
      microM was found in the samples. Maximum specific binding values in ghost and
      solubilized extracts were 9.0 pmol/mg of protein and 1.0 pmol/mg of protein,
      respectively. The low dissociation constant was confirmed by kinetic studies with
      a value of 0.16 microM. Specific [3H]-cGMP binding was inhibited by cAMP, cGMP,
      and cIMP with KD values of 0.22 microM, 0.09 microM, and 0.17 microM,
      respectively. Unlabeled cGMP and cIMP inhibited [3H]-cGMP binding completely
      whereas cAMP inhibited only 70%. The membrane-localized cGMP-binding protein
      discriminates between cyclic and noncyclic nucleotides, since GMP, IMP, and AMP
      were unable to displace [3H]-cGMP. A zwitterionic detergent, CHAPS (3-[(3
      cholamidopropyl)dimethylammonio]-1-propanesulfate), was able to solubilize a
      protein with identical binding affinity. The results of this study show that
      erythrocyte ghosts possess a cGMP-binding protein which is not a kinase (due to a
      similar affinity for cAMP, cGMP, and cIMP) or phosphodiesterase (due to the
      inability of IBMX, 3-isobutyl-1-methylxanthine, to inhibit specific [3H]-cGMP
      binding). We hypothesize that this protein is the cell membrane cGMP transporter.

PMID- 9283088
TI  - Cholesterol as modulator of receptor function.
AB  - The modulatory effect of cholesterol on the function of two structurally related
      peptide receptors, the oxytocin receptor and the brain cholecystokinin receptor
      in plasma membranes as well as in intact cells, was analyzed. Different
      approaches for cholesterol modification were applied: (i) depletion and reloading
      of cholesterol mediated by methyl-beta-cyclodextrin and cholesterol-methyl-beta
      cyclodextrin, respectively, in a reversible manner; (ii) mild treatment of the
      plasma membranes with cholesterol oxidase under control of the membrane fluidity
      as measured by fluorescence anisotropy of diphenylhexatriene; and (iii) filipin
      pretreatment of membranes. The results allowed us to distinguish two mechanisms
      of cholesterol affecting the ligand-binding function of receptors: changes of the
      membrane fluidity as demonstrated for the cholecystokinin receptor, or a
      putatively specific cholesterol-receptor interaction as shown for the oxytocin
      receptor. This was confirmed in a structure-activity analysis with a variety of
      sterol analogues substituting for cholesterol in the membranes. While the agonist
      binding of the cholecystokinin receptor was supported by each of the tested
      steroids and was well correlated with the corresponding fluorescence anisotropy
      values, a stringent and unique requirement of the oxytocin receptor's affinity
      state for structural features of the sterol molecule was found. The molecular
      requirements differ both from those postulated for sterol-phospholipid
      interactions and from those known to be necessary for the functional activity of
      other proteins. The different behavior of both peptide receptors concerning the
      cholesterol dependence of their ligand binding was also present in vivo at the
      level of signal transduction. The results suggest that cholesterol can modulate
      receptor function by two distinct mechanisms, by changes of the membrane
      fluidity, and/or by a highly specific molecular interaction.

PMID- 9283089
TI  - Temperature dependence of backbone dynamics in loops of human mitochondrial heat
      shock protein 10.
AB  - A highly flexible, yet conserved polypeptide loop of Hsp10 mediates binding to
      Hsp60 in the course of chaperonin-dependent protein folding. Previous transferred
      nuclear Overhauser effect (trNOE) studies with peptides based on the mobile loop
      of the Escherichiacoli and bacteriophage T4 Hsp10s suggested that the mobile loop
      adopts a characteristic hairpin turn upon binding to the E. coli Hsp60 GroEL. In
      this paper, we identify the sequence and characterize the nascent structure and
      dynamics of the 18-residue mobile loop in the 15N-enriched human Hsp10. We also
      identify four residues of another flexible loop, the roof beta hairpin. The
      mobile loop and/or roof beta hairpin of several subunits are absent from the X
      ray crystal structure of human Hsp10. NMR data suggest that the mobile loop of
      Hsp10 preferentially samples a hairpin conformation despite the fact that the
      backbone motion resembles that of a disordered polypeptide. Analysis of backbone
      dynamics by measurement of 15N relaxation times, T1 and T2, and the 1H-15N
      nuclear Overhauser effect (1H-15N NOE) indicates that motion is greatest near the
      center of the loop. Inversion of the temperature dependence of the T1 near the
      center of the loop marks a transition to motion with a dominant time scale of
      less than 3 ns. Analysis of the relaxation data by spectral density mapping shows
      that subnanosecond motion increases uniformly along the loop at elevated
      temperatures, whereas nanosecond motion increases near the ends of the loop and
      decreases near the center of the mobile loop. The transition to dominance by fast
      motion in the center of the loop occurs at a distance from the well-structured
      part of Hsp10 that is equal to the persistence length of an unstructured
      polypeptide. Simulation of the spectral density function for the 15N resonance
      and its temperature dependence using the Lipari-Szabo formalism suggests that the
      dominant time scales of loop motion range from 0.6 to 18 ns. For comparison, the
      time scale for molecular rotation of the 70 kDa Hsp10 heptamer is estimated to be
      37 ns. Complex behavior of the T2 relaxation time indicates that motion also
      occurs on longer time scales. All of the modes of loop motion are likely to have
      an impact on Hsp10/Hsp60 interaction and therefore affect Hsp10/Hsp60 function as
      a chaperonin.

PMID- 9283090
TI  - Substrate binding-induced changes in the EPR spectra of the ferrous nitric oxide
      complexes of neuronal nitric oxide synthase.
AB  - A versatile diatomic physiological messenger, nitric oxide (NO), is
      biosynthesized by a group of flavo-heme enzymes, the nitric oxide synthases. We
      have examined the active site of the neuronal isoform by EPR spectroscopy of the
      ferrous nitric oxide complex. The nitric oxide complex of the substrate-free
      enzyme exhibits a cytochrome P450-type EPR spectrum typical of a hexacoordinate
      NO-heme complex with a non-nitrogenous proximal axial heme ligand. The NO complex
      of the substrate-free enzyme is rather unstable and spontaneously converts to a
      cytochrome P420 type pentacoordinate denatured form. Binding of L-arginine (l
      Arg) enhances the stability of the hexacoordinate NO form. The EPR spectrum of
      the NO adduct of the enzyme-substrate complex has an increased g-anisotropy and
      well-resolved hyperfine couplings due to the 14N of nitric oxide. Significant
      perturbations in the NO EPR spectrum were observed upon Nomega-monomethyl-L-Arg
      and Nomega-hydroxy-L-Arg binding. The perturbations in the EPR spectrum indicate
      that L-Arg and its derivatives bind on the distal site of the heme in very close
      proximity to the bound NO to cause alterations in the heme-NO coordination
      structure. Interactions between the bound NO and the substrate or its analogues
      appear to affect the Fe-NO geometry, resulting in the observed spectral changes.
      We infer that analogous interactions with oxygen might be involved in the
      hydroxylation events during enzyme catalysis of nitric oxide synthase.

PMID- 9283091
TI  - Water accessibility to the tryptophan indole N-H sites of gramicidin A
      transmembrane channel: detection of positional shifts of tryptophans 11 and 13
      along the channel axis upon cation binding.
AB  - Gramicidin A analogues, in which one of four Trp residues was selectively
      substituted by carbon-deuterated Trp, were incorporated into phospholipid
      liposomes and their Raman spectra were recorded in the absence and presence of
      Na+. Detailed analyses of the Raman spectra have revealed the conformation,
      strength of hydrophobic interaction, and water accessibility of each individual
      Trp residue of the gramicidin transmembrane channel. The absolute value of the
      torsion angle chi2,1 about the CalphaCbeta-C3C2 linkage is found to be 94 degrees
      +/- 6 degrees in both the cation-free and Na+-bound states. The Trp side chains
      are generally involved in strong hydrophobic interactions with the lipid acyl
      chains of the membrane and/or with another Trp residue. The water accessibility
      to the indole N1H site is in the order Trp-15 > Trp-13 >> Trp-11 > Trp-9 in the
      cation-free state. In the Na+-bound state, however, the water accessibility
      significantly decreases for Trp-13 and increases for Trp-11 without change for
      Trp-15 and -9. The site-specific changes of water accessibility are explained by
      a combination of positional shifts of Trp-13 and -11 toward the channel center
      and the channel mouth, respectively. Model building has shown that such
      positional shifts of Trp indole rings can be linked with deflections of amide
      C&dbd;O bonds toward the channel pore, suggesting a cation-induced conformational
      transition of the channel backbone structure.

PMID- 9283093
TI  - Chromophore-anion interactions in halorhodopsin from Natronobacterium pharaonis
      probed by time-resolved resonance Raman spectroscopy.
AB  - Halorhodopsin of Natronobacterium pharaonis which acts as a light-driven chloride
      pump is studied by time-resolved resonance Raman spectroscopy. In single-beam
      experiments, resonance Raman spectra were obtained of the parent state HR578 and
      the first thermal intermediate HR520. The parent state is structural
      heterogeneous including ca. 80% all-trans and 20% 13-cis isomers. The resonance
      Raman spectra indicate that the all-trans conformer exhibits essentially the same
      chromophoric structure as in the parent states of bacteriorhodopsin or
      halorhodopsin from Halobacterium salinarium. Special emphasis of the resonance
      Raman spectroscopic analysis was laid on the C=C and C=N stretching region in
      order to probe the interactions between the protonated Schiff base and various
      bound anions (chloride, bromide, iodide). These investigations were paralleled by
      spectroscopic studies of retinal Schiff base model complexes in different
      solvents in an attempt to determine the various parameters which control the C=C
      and C=N stretching frequencies. From these data, it was concluded that in the
      parent state the anion is not involved in hydrogen bonding interactions with the
      Schiff base proton but is presumably bound to a nearby (positively charged) amino
      acid residue. On the other hand, the anion still exerts an appreciable effect on
      the chromophore structure which is, for instance, reflected by the variation of
      the isomer composition in the presence of different anions and in the anion
      depleted form. In contrast to the parent state, the intermediate HR520 reveals
      frequency shifts of the C=N stretching in the presence of different anions. These
      findings indicate a closer proximity of the bound anion to the Schiff base proton
      which is sufficient for hydrogen bonding interactions. These changes of the anion
      chromophore interaction upon transition from HR578 to HR520 may be related to the
      coupling of the chromophore movement with the anion translocation.

PMID- 9283092
TI  - Destabilization of the Ca2+-ATPase of sarcoplasmic reticulum by thiol-specific,
      heat shock inducers results in thermal denaturation at 37 degrees C.
AB  - A number of protein reactive compounds, including the thiol reagents diamide and
      arsenite, are known inducers of heat shock protein (HSP) synthesis and
      thermotolerance. These compounds are thought to damage cellular protein, which
      has been proposed to serve as the signal for induction. The specific mechanism of
      protein damage and its relation to thermal denaturation are unknown. The Ca2+
      ATPase of sarcoplasmic reticulum, a membrane protein that contains 24 cys
      residues, was used to determine the effect of diamide, arsenite, N-ethylmaleimide
      (NEM), and the cys-specific probes Br-DMC and IAEDANS, which label one or two
      specific cys residues, respectively, on protein conformation and stability. The
      Ca2+-ATPase was chosen because diamide has been shown to affect the thermal
      properties of a class of membrane proteins of CHO cells (Freeman et al., 1995).
      The labeling of one or two thiols has no effect on activity or conformation,
      while more extensive reaction (but with less than approximately five to eight
      groups titrated) results in destabilization of the Ca2+-ATPase such that it
      denatures thermally at 37 degrees C. Higher levels of titration result in greater
      destabilization such that the protein is no longer stable at room temperature,
      with the production of a state similar to the thermally denatured state as
      assayed by activity, differential scanning calorimetry, ANS binding, and light
      scattering. The fractional denaturation induced by these thiol reagents,
      determined by the decrease in the heat absorbed during thermal denaturation, is
      directly proportional to inactivation of ATPase activity. Thus, inactivation of
      the Ca2+-ATPase by thiol reagents occurs because of denaturation not through
      oxidation of essential thiols. These results indicate that these thiol-specific
      heat shock inducers function by two mechanisms: (1) destabilization of proteins
      such that they thermally denature at 37 degrees C and (2) direct denaturation,
      apparently driven by thermal processes at room temperature, following more
      extensive reaction which results in extreme destabilization. We suggest that
      these are general mechanisms by which heat shock inducers damage proteins.

PMID- 9283094
TI  - Characterization of the chicken telokin heterogeneity by time-of-flight mass
      spectrometry.
AB  - Chicken gizzard telokin was purified to apparent homogeneity by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. This preparation yielded upon mass
      spectrometry analysis seven mass peaks spanning from 15 858 to 17 100 Da. Anion
      exchange-high performance liquid chromatography of the purified telokin revealed
      a high diversity of telokin molecules. By combining protein chemistry to
      chromatography and mass spectrometry, the telokin heterogeneity was analyzed.
      Three acetylated N-termini were found, AMI, MIS, and SGR. Cyanogen bromide
      cleavage of telokin yielded six different C-terminal peptides corresponding to
      the removal of one to six C-terminal glutamyl residues from the protein sequence
      deduced from the cDNA. Phosphorylation of telokin was detected, thus increasing
      the heterogeneity of the telokin preparation. In addition, peptide sequencing has
      shown that telokin contained either an aspartyl or a glutamyl residue at position
      27, probably resulting from chicken polymorphism.

PMID- 9283095
TI  - Troponin T and Ca2+ dependence of the distance between Cys48 and Cys133 of
      troponin I in the ternary troponin complex and reconstituted thin filaments.
AB  - Contraction of vertebrate striated muscle is regulated by the interaction of Ca2+
      with the heterotrimeric protein troponin (Tn), composed of troponin-C (TnC),
      troponin-I (TnI), and troponin-T (TnT). Although much is known about the Ca2+
      induced conformational changes in TnC, the Ca2+-binding subunit of Tn, little is
      known about how TnI, the inhibitory subunit, responds to the binding of Ca2+ to
      TnC. In this work, we used resonance energy transfer to measure the distance
      between probes attached at Cys48 and Cys133 in the N- and C-terminal domains,
      respectively, of TnI. A mutant rabbit skeletal TnI, TnI48/133 (C64S), was
      constructed by converting Cys64 into Ser. The remaining two thiols at Cys48 and
      Cys133 were labeled with the fluorescent donor 1,5-IAEDANS, and the
      nonfluorescent acceptor, DAB-Mal. We found an interprobe distance of
      approximately 41 A for both uncomplexed TnI and TnI in the binary complex with
      TnC. This distance increased to 51 A in the ternary Tn complex with TnT. These
      distances did not change significantly on binding of Ca2+ to TnC. In the
      reconstituted thin filament, this distance remained to be 50 A in the presence of
      saturating Ca2+, but increased to approximately 66 A on removing Ca2+ with EGTA
      in the presence of Mg2+. Our results indicate firstly that while TnC has only
      small effects on the global conformation of TnI, the presence of TnT in the
      ternary Tn complex gives rise to an apparent elongation of TnI. Secondly, whereas
      there is no detectable Ca2+-dependent change in the global conformation of TnI in
      the Tn complex free in solution, the removal of Ca2+ caused a substantial
      separation of the N- and C-terminal TnI regions in the reconstituted thin
      filament, owing to the interaction between the C-terminal region of TnI and actin
      in the relaxed state.

PMID- 9283096
TI  - A kinetically active site in the C-lobe of human transferrin.
AB  - Release of iron from transferrin, the iron-transporting protein of the
      circulation, is a concerted process involving remote amino acid residues as well
      as those at the two specific iron-binding sites of the protein. Previous studies
      of fluoresceinated transferrin have suggested Lys 569 as a kinetically active
      site in the C-terminal lobe of the protein. We have therefore turned to site
      directed mutagenesis to investigate the role of Lys 569 in the release process at
      pH 5.6, the pH of the endosome where iron is transferred from transferrin to the
      iron-dependent cell. Mutation of positively charged Lys 569 to an uncharged Gln
      results in a protein in which release of iron from the mutated lobe to
      pyrophosphate is slowed by a factor of 15-20 and in which release kinetics switch
      from a complex saturation-linear to a simple saturation function. Acceleration of
      release by chloride is also substantially less than in native transferrin. When
      Lys 569 is replaced by a positively charged Arg, in contrast, observed release
      rates and chloride dependence are close to those of the native protein. The
      mechanism of release from the C-lobe site therefore appears to be sensitive to
      positive charge at position 569. Binding of chloride or other simple anion
      accelerates and is essential for release from the C-lobe; a muted response of
      K569Q to chloride concentration suggests that Lys 569 may function as a
      kinetically active anion-binding residue in the C-lobe. Despite the kinetic
      effects of the K569 mutation on iron release, rates of iron uptake by K562 cells
      from the C-lobes of native, K569Q, and K569R proteins are almost identical. In
      contrast to the C-lobe, iron release from the N-lobe is insensitive to charge at
      residue 233, the site in that lobe homologous to residue 569, with chloride
      retarding rather than accelerating release. K233, therefore, is not a kinetically
      active anion-binding site in the N-lobe. Release mechanisms differ substantially
      in the two lobes of transferrin despite the identity of ligands and their nearly
      identical arrangements in the lobes.

PMID- 9283097
TI  - Glutamate-119 of the large alpha-subunit is the catalytic base in the hydration
      of 2-trans-enoyl-coenzyme A catalyzed by the multienzyme complex of fatty acid
      oxidation from Escherichia coli.
AB  - Glu139 of the large alpha-subunit of the multienzyme complex of fatty acid
      oxidation from Escherichia coli was identified as the catalytic residue of enoyl
      CoA hydratase [Yang, S.-Y., He, X.-Y., & Schulz, H. (1995) Biochemistry 34, 6441
      6447]. To determine whether any of the other conserved protic residues is
      directly involved in the hydratase catalysis, the multienzyme complexes with
      either an alpha/Asp69 --> Asn or an alpha/Glu119 --> Gln mutation were
      overproduced and characterized. The catalytic properties of 3-ketoacyl-CoA
      thiolase and l-3-hydroxyacyl-CoA dehydrogenase of the mutant complexes were
      almost unaffected. The amidation of Asp69 and Glu119 caused a 7.6- and 88-fold
      decrease, respectively, in the kcat of enoyl-CoA hydratase without a significant
      change in the Km value of the hydratase as well as a 5.9- and 62-fold increase,
      respectively, in the Km of Delta3-cis-Delta2-trans-enoyl-CoA isomerase with a
      very small decrease in the kcat of the latter enzyme. The data suggest that the
      carboxyl group of Glu119 is particularly important to the catalytic activity of
      enoyl-CoA hydratase. Furthermore, the wild-type hydratase shows a bell-shaped pH
      dependence of the kcat/Km with pKa values of 5.9 and 9.2, whereas the Glu119 -->
      Gln mutant hydratase has only a single pKa of 9.5. A simple explanation for these
      observations is that a deprotonated Glu119 and a protonated Glu139 are required
      for the high kcat of the enoyl-CoA hydratase. The results of site-directed
      mutagenesis studies, together with the structural information about the spatial
      arrangement of two conserved glutamate residues of rat liver enoyl-CoA hydratase
      [Engel, C. K., Mathieu, M., Zeelen, J. P., Hiltunen, J. K., and Wierenga, R. K.
      (1996) EMBO J. 15, 5135-5145] to which Glu119 and Glu139 of the large alpha
      subunit correspond, lead to the conclusion that the gamma-carboxyl group of
      Glu119 serves as the second general acid-base functional group in catalyzing the
      hydration of 2-trans-enoyl-CoA.

PMID- 9283099
TI  - Fractal analysis of striatal dopamine re-uptake sites.
AB  - Spatial variation in regional blood flow, metabolism and receptor density within
      the brain and in other organs is measurable even with a low spatial resolution
      technique such as emission tomography. It has been previously shown that the
      observed variance increases with increasing number of subregions in the
      organ/tissue studied. This resolution-dependent variance can be described by
      fractal analysis. We studied striatal dopamine re-uptake sites in 39 healthy
      volunteers with high-resolution single-photon emission tomography using iodine
      123 labelled 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([123I]beta-CIT). The
      mean fractal dimension was 1.15+/-0.07. The results indicate that regional
      striatal dopamine re-uptake sites involve considerable spatial heterogeneity
      which is higher than the uniform density (dimension=1.00) but much lower than
      complete randomness (dimension=1.50). There was a gender difference, with females
      having a higher heterogeneity in both the left and the right striatum. In
      addition, we found striatal asymmetry (left-to-right heterogeneity ratio of
      1.19+/-0.15; P<0.001), suggesting functional hemispheric lateralization
      consistent with the control of motor behaviour and integrative functions.

PMID- 9283100
TI  - Whole-body positron emission tomography in clinical oncology: comparison between
      attenuation-corrected and uncorrected images.
AB  - The clinical need for attenuation correction of whole-body positron emission
      tomography (PET) images is controversial, especially because of the required
      increase in imaging time. In this study, regional tracer distribution in
      attenuation-corrected and uncorrected images was compared in order to delineate
      the potential advantages of attenuation correction for clinical application. An
      ECAT EXACT scanner and a protocol including five to seven bed positions, emission
      scans of 9 min and post-injection transmission scans of 10 min per bed position
      were used. Uncorrected and attenuation-corrected images were reconstructed by
      filtered backprojection. In total, 109 areas of focal fluorine-18
      fluorodeoxyglucose (FDG) uptake in 34 patients undergoing PET for the staging of
      malignancies were analysed. To measure focus contrast, a ratio of focus (target)
      to background average countrates (t/b ratio) was obtained from transaxial slices
      using a region of interest technique. Calculation of focus diameters by a
      distance measurement tool and visual determination of focus borders were
      performed. In addition, images of a body phantom with spheres to simulate focal
      FDG uptake were acquired. Transmission scans with and without radioactivity in
      the phantom were used with increasing transmission scanning times (2-30 min). The
      t/b ratios of the spheres were calculated and compared for the different imaging
      protocols. In patients, the t/b ratio was significantly higher for uncorrected
      images than for attenuation-corrected images (5.0+/-3.6 vs 3.1+/-1.4; P<0.001).
      This effect was independent of focus localization, tissue type and distance to
      body surface. Compared with the attenuation-corrected images, foci in uncorrected
      images showed larger diameters in the anterior-posterior dimension (27+/-14 vs
      23+/-12 mm; P<0.001) but smaller diameters in the left-right dimension (19+/-11
      vs 21+/-11 mm; P<0.001). Phantom data confirmed higher contrast in uncorrected
      images compared with attenuation-corrected images. It is concluded that, although
      distortion of foci was demonstrated, uncorrected images provided higher contrast
      for focal FDG uptake independent of tumour localization. In most clinical
      situations, the main issue of whole-body PET is pure lesion detection with the
      highest contrast possible, and not quantification of tracer uptake. The present
      data suggest that attenuation correction may not be necessary for this purpose.

PMID- 9283101
TI  - Clinical value of triple-energy window scatter correction in simultaneous dual
      isotope single-photon emission tomography with 123I-BMIPP and 201Tl.
AB  - To improve the image quality in simultaneous dual-isotope single-photon emission
      tomography (SPET) with iodine-123 labelled 15-(p-iodophenyl)-3
      methylpentadecanoic acid (BMIPP) and thallium-201, we applied the triple-energy
      window method (TEW) for correction of the cross-talk and scatter artifact.
      Seventy-one patients with coronary artery disease were included. 201Tl cross-talk
      into the 123I acquisition window (group 1, n = 30) and 123I cross-talk into the
      201Tl window (group 2, n = 41) were studied. In group 1, 123I images were first
      obtained (single-isotope images), followed by 201Tl injection and SPET
      acquisition using dual-isotope windows (dual-isotope images). In group 2, the
      order was reversed. The dual-isotope SPET images with and without TEW were
      compared with the single-isotope images. Qualitative evaluation was performed by
      scoring the segmental defect pattern. Detectability of the mismatched fatty acid
      metabolism on dual-isotope SPET was evaluated by receiver operating
      characteristic (ROC) curve analysis. Segmental defect pattern agreement between
      dual and corrected single images was significantly improved by TEW correction
      (P<0.01). The agreement was particularly improved in segments with absence of
      uptake. There was no significant difference between TEW-corrected dual-isotope
      SPET and corresponding single-isotope SPET with regard to either % defect count
      or background activity. Mismatched fatty acid metabolism depicted by dual-isotope
      SPET predicted abnormal wall motion more accurately with TEW than without TEW.
      With TEW, a practical method for scatter and cross-talk correction in clinical
      settings, simultaneous dual 123I-BMIPP/201Tl SPET is feasible for the assessment
      of myocardial perfusion/metabolism mismatch.

PMID- 9283102
TI  - Attenuation correction by simultaneous emission-transmission myocardial single
      photon emission tomography using a technetium-99m-labelled radiotracer: impact on
      diagnostic accuracy.
AB  - Irregular photon attenuation may limit the diagnostic accuracy of myocardial
      single-photon emission tomography (SPET). The aim of this study was to quantify
      the potential benefit of attenuation correction by simultaneous emission and
      transmission imaging for the detection of coronary artery disease (CAD) of
      vessels supplying the inferoposterior wall segments. In 25 male patients with
      >/=50% stenoses of the right coronary artery and/or circumflex artery but without
      significant narrowing of the left anterior descending artery, stress studies
      using technetium-99m tetrofosmin (400 MBq) were carried out with and without
      attenuation correction. A dual-head camera with L-shaped detector positioning was
      equipped with two scanning gadolinium-153 line sources. Tomograms were
      reconstructed and quantified using circumferential count rate profiles of
      myocardial activity (two in each patient). The profiles were compared with the
      respective normal ranges obtained from a database of 25 male patients with a <10%
      likelihood of CAD. In patients without CAD, the maximal differences in count
      density of different wall segments were reduced from 29.0% in non-corrected (NC)
      studies to 9.5% in attenuation-corrected (AC) studies. In particular, the
      inferoposterior and septal wall segments were represented by significantly
      increased relative count densities after attenuation correction. The effects of
      attenuation correction proved independent of body mass. In patients with CAD,
      segmental count densities were abnormal in 84% of the NC studies and 100% of the
      AC studies. In single-vessel disease the stenotic vessel was identified in 66% of
      cases by NC studies and in 100% by AC studies. In AC studies, the extent and
      depth of defects exceeded those in NC studies. For the detection of CAD of the
      right coronary artery, the receiver operating characteristic (ROC) curves
      relating to the AC studies demonstrated improved discrimination capacity
      (P<0.05). ROC analysis of CAD detection yielded normalcy rates of 82% (NC) and
      94% (AC) for the circumflex artery and 65% (NC) and 97% (AC) for the right
      coronary artery area at a sensitivity level of 95%. It is concluded that
      attenuation correction using the above system may enhance the diagnostic accuracy
      of myocardial SPET when inferoposterior wall segments are to be evaluated.

PMID- 9283103
TI  - A comparison of 99mTc-MIBI myocardial SPET with electron beam computed tomography
      in the assessment of coronary artery disease.
AB  - We compared technetium-99m methoxyisobutylisonitrile (MIBI) myocardial perfusion
      single-photon emission tomography (SPET) (MPS) and electron beam computed
      tomography (EBCT) in order to assess their respective value in the detection of
      coronary artery disease (CAD). 99mTc-MIBI SPET (stress-resting) and EBCT studies
      were performed in 51 patients with suspected CAD who underwent coronary
      angiography (CAG). CAG showed that of the 51 patients, 36 had coronary stenosis
      >/=50% while 15 had normal results. A moderate positive rank correlation was
      found between coronary calcification detected by EBCT and MPS score (rs=0.5283,
      P<0.01). The concordance between EBCT and MPS for the evaluation of CAD was 72.5%
      (37/51). The sensitivity of EBCT in detecting CAD in 51 patients was comparable
      to that of MPS (81% vs 94%, NS). However, the accuracy of EBCT was lower than
      that of MPS (78% vs 94%, P<0.025). As regards the detection of individual
      coronary artery disease, there was no significant difference in sensitivity
      between EBCT and MPS (65% vs 75%, NS); however, the specificity and accuracy of
      EBCT were lower than those of MPS (specificity: 77% vs 95%, P<0.005; accuracy 71%
      vs 85%, P<0.005). The sensitivity, specificity and accuracy of MPS in detecting
      single-vessel disease were higher than those of EBCT (sensitivity: 86% vs 42%,
      P<0.025; specificity: 96% vs 70%, P<0.025; accuracy: 93% vs 61%, P<0.005).
      However, no significant differences in the sensitivity, specificity and accuracy
      of MPS and EBCT were found in respect of multivessel disease. IN CONCLUSION:
      99mTc-MIBI myocardial perfusion SPET and EBCT provide different information in
      the assessment of CAD. The sensitivity of EBCT for the detection of CAD is
      comparable with that of MPS; however, the specificity and accuracy of EBCT are
      lower than those of MPS. More reliable results will be obtained if both
      myocardial perfusion SPET and EBCT are performed.

PMID- 9283104
TI  - Adenosine technetium-99m sestamibi single-photon emission tomography for the
      assessment of jeopardized myocardium early after acute myocardial infarction.
      Paradoxical scintigraphic underestimation of jeopardized myocardium in patients
      with a severe infarct-related stenosis.
AB  - This study investigated the value of technetium-99m sestamibi scintigraphy in
      identifying patients at risk for post-infarct ischaemia (=jeopardized
      myocardium), especially within the reperfused infarct region. In 51 patients with
      a recent (<1 month) myocardial infarction, adenosine 99mTc-sestamibi single
      photon emission tomography (SPET) and dobutamine stress echocardiography (DSE)
      were performed and correlated with the presence of significant coronary artery
      stenosis [% diameter stenosis (DS) >50%] on quantitative coronary angiography.
      Regional perfusion activity was analysed semi-quantitatively (score 0-4) on a 13
      segment left ventricular model. DSE was used for the estimation of the infarct
      size (low-dose DSE) and for concomitant evaluation of ischaemia (high-dose DSE).
      A reversible perfusion defect within the infarct region was observed in 20 of the
      37 patients with a significant infarct-related lesion (sensitivity of 54%) and
      only in one patient without a significant infarct-related lesion (specificity of
      93%). Further analysis revealed that the scintigraphic assessment of jeopardized
      myocardium was fairly good in patients with a moderate (DS 51%-64%) infarct
      related stenosis but was inadequate in patients with a severe (DS>/=65%) infarct
      related stenosis (sensitivity of 80% vs 36%, P<0.01), while the echocardiographic
      detection of ischaemia was not influenced by stenosis severity (sensitivity of
      73% in both subgroups). This scintigraphic underestimation of jeopardized
      myocardium was mainly related to a severely impaired myocardial perfusion under
      baseline conditions, as was evidenced by a significantly more severe rest
      perfusion score in the infarct region in patients with a severe stenosis as
      compared to those with a moderate stenosis (average score: 1.5+/-0.7 vs 2.1+/
      0.6, P<0.01), while infarct size on echocardiography was similar for both
      subgroups. It may be concluded that early after an acute myocardial infarction,
      adenosine 99mTc-sestamibi SPET may underestimate reperfused but still jeopardized
      myocardium, particularly in patients with a severe infarct-related stenosis. In
      these patients the evaluation of the ischaemic burden on rest-stress scintigraphy
      is hampered by the presence of a severely impaired myocardial perfusion in
      resting conditions.

PMID- 9283105
TI  - Myocardial damage assessed by indium-111-antimyosin: correlation with persistent
      enteroviral ribonucleic acid in dilated cardiomyopathy.
AB  - The persistence of enteroviral ribonucleic acid (RNA) in the myocardium has been
      implicated as a pathogenetic factor in idiopathic dilated cardiomyopathy.
      Enteroviral persistence may lead to myocardial cell membrane damage, resulting in
      increased uptake of antimyosin antibodies. To further evaluate this hypothesis, a
      direct comparison of myocardial antimyosin uptake with the presence of
      enteroviral RNA was performed in ten patients (one female, nine male; 53+/-8
      years) with chronic dilated cardiomyopathy. Planar antimyosin images were
      obtained 48 h after the injection of indium-111-labelled antimyosin Fab. Using a
      region of interest technique, the heart to lung uptake ratio (HLR) was calculated
      as a semiquantitative parameter of myocardial tracer uptake. Cardiac
      catheterization was performed to assess left ventricular function and to obtain
      myocardial biopsy samples. In the biopsy samples, gene amplification by
      polymerase chain reaction (PCR) was used to specifically detect enteroviral RNA.
      In the ten patients, the left ventricular ejection fraction was 39%+/-11% and the
      end-diastolic volume 131+/-46 ml/m2. The HLR was 1.72+/-0.21 and showed no
      correlation with functional parameters. In two patients with a positive PCR
      consistent with persisting enteroviral RNA, the HLR was not higher than that in
      eight patients with a negative PCR (1.46+/-0. 18 vs 1.78+/-0.18, respectively).
      These results suggest that increased uptake of 111In-antimyosin in chronic
      idiopathic dilated cardiomyopathy cannot be explained by pure persistence of
      enteroviral RNA. Other pathogenetic factors such as myocardial autoantibodies or
      microvascular spasm may be responsible for myocyte membrane damage detected by
      antimyosin.

PMID- 9283106
TI  - Increased cardiac sympathetic activity in patients with hypothyroidism as
      determined by iodine-123 metaiodobenzylguanidine scintigraphy.
AB  - Clinical manifestations of hypothyroidism, such as bradycardia, suggest decreased
      sympathetic tone. However, previous studies in patients with hypothyroidism have
      suggested that increased plasma noradrenaline (NA) levels represent enhanced
      general sympathetic activity. As yet, cardiac sympathetic activity (CSA) in
      hypothyroidism has not been clarified. To evaluate CSA in patients with
      hypothyroidism, iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy was
      performed in eight patients with hypothyroidism before therapy and in ten normal
      control patients. Planar images were obtained at 15 min and 4 h after injection
      of MIBG. The ratio of early myocardial uptake to the total injected dose (MU) and
      myocardial clearance of MIBG within 4 h p.i. (MC) were calculated. Plasma NA was
      also measured, and echocardiography was performed in all patients. Those patients
      with hypothyroidism in the euthyroid state after medical therapy were also
      evaluated in a similar manner. Left ventricular ejection fraction, measured by
      echocardiography, did not differ significantly between the groups. NA, MU and MC
      were significantly higher in patients with hypothyroidism than in controls, and
      all parameters were decreased after therapy. MC was well correlated with NA in
      hypothyroidism (r=0.86) before therapy. We conclude that CSA is increased in
      patients with hypothyroidism, in parallel with the enhanced general sympathetic
      activity.

PMID- 9283107
TI  - Comparison of fluorine-18 fluorodeoxyglucose positron emission tomography and
      technetium-99m methoxyisobutylisonitrile scintimammography in the detection of
      breast tumours.
AB  - The aim of this study was to compare, in breast cancer patients, the diagnostic
      accuracy of positron emission tomography (PET) using fluorine-18
      fluorodeoxyglucose (FDG) and scintimammography (SMM) using technetium-99m
      methoxyisobutylisonitrile (MIBI). A total of 20 patients (40 breasts with 22
      lesions) were evaluated serially with MIBI and, on the following day, with FDG.
      For SMM, planar and single-photon emission tomography imaging in the prone
      position was performed starting at 10 min following the injection of MIBI (740
      MBq). For PET, scans were acquired 45-60 min after the injection of FDG (370 MBq)
      and attentuation correction was performed following transmission scans. Results
      from SMM and PET were subsequently compared with the histopathology results. True
      positive results were obtained in 12/13 primary breast cancers (mean diameter=29
      mm, range 8-53 mm) with both FDG and MIBI. False-negative results were obtained
      in two local recurrences (diameter <9 mm) with both FDG and MIBI. In benign
      disease, FDG and MIBI did not localize three fibrocystic lesions, two
      fibroadenomas and one inflammatory lesion (true-negative), but both localized one
      fibroadenoma (false-positive). Collectively, the results demonstrate a
      sensitivity of 92%, and a specificity of 86%, for primary breast cancer
      regardless of whether FDG or MIBI was used. In contrast to MIBI scintigraphy, FDG
      PET scored the axillae correctly as either positive (metastatic disease) or
      negative (no axillary disease) in all 12 patients. The tumour/non-tumour ratio
      for MIBI was 1.97 (range 1.43-3.1). The mean standard uptake value (SUV) for FDG
      uptake was 2.57 (range 0.3-6.2). The diagnostic accuracy of SMM was equivalent to
      that of FDG PET for the detection of primary breast cancer. For the detection of
      in situ lymph node metastases of the axilla, FDG seems to be more sensitive than
      99mTc-MIBI.

PMID- 9283108
TI  - Technetium-99m (V)-dimercaptosuccinic acid: normal accumulation in the breasts.
AB  - Technetium-99m (V)-dimercaptosuccinic acid (DMSA) is a tumour-imaging agent which
      has been used to evaluate medullary thyroid cancer and soft tissue tumours.
      Physiological uptake has been demonstrated in the kidneys, nasal mucosa and blood
      pool. In addition to positive accumulation in these sites, uptake in the breasts
      has been noted. The purpose of this retrospective study was to evaluate the
      accumulation of 99mTc (V)-DMSA in the normal breasts of 83 patients. There was no
      accumulation in male breasts. On the other hand, 24 of 51 female patients showed
      bilateral symmetrical accumulation in the breasts. Positive uptake was seen in 16
      of 23 patients (70%) between 15 and 50 years old, but in only 7 of 25 (28%) above
      50 years old. One out of three patients (33%) under 15 years old showed positive
      breast uptake. In conclusion, the female breasts should be included in the
      description of a pattern of normal biodistribution of 99mTc (V)-DMSA.

PMID- 9283109
TI  - Differentiation of clinically non-functioning pituitary adenomas from meningiomas
      and craniopharyngiomas by positron emission tomography with [18F]fluoro-ethyl
      spiperone.
AB  - The differential diagnosis among various types of non-functioning sellar and
      parasellar tumours is sometimes difficult using currently available methods of
      morphological imaging. The aim of this study was to define whether assessment of
      the uptake of [18F]fluoro-ethyl-spiperone (FESP) with positron emission
      tomography (PET) could be helpful for the differential diagnosis of pituitary
      adenomas and other parasellar lesions, and for establishing the appropriate
      therapeutic approach. The population examined comprised 16 patients with the
      diagnosis of primary tumour of the sellar/parasellar region who were waiting to
      undergo surgical treatment. The results demonstrated that PET with [18F]FESP is a
      very specific method for differentiating adenomas from craniopharyngiomas and
      meningiomas. The visual interpretation of images allows such differentiation at
      approximately 70 min after tracer injection. Semiquantitative analysis of the
      dynamic PET data confirmed the results of visual interpretation, demonstrating
      that the uptake of [18F]FESP was consistently (i.e. throughout the series) at
      least two- to threefold higher in non-functioning adenomas than in other
      parasellar tumours as early as 70 min after tracer injection, and that it
      increased still further thereafter. It is concluded that PET with [18F]FESP might
      be of clinical value in those cases in which the differential diagnosis among
      various histological types of sellar tumour is uncertain with conventional
      methods.

PMID- 9283110
TI  - Effect of partial volume correction on muscarinic cholinergic receptor imaging
      with single-photon emission tomography in patients with temporal lobe epilepsy.
AB  - Animal experiments and preliminary results in humans have indicated alterations
      of hippocampal muscarinic acetylcholine receptors (mAChR) in temporal lobe
      epilepsy. Patients with temporal lobe epilepsy often present with a reduction in
      hippocampal volume. The aim of this study was to investigate the influence of
      hippocampal atrophy on the quantification of mAChR with single photon emission
      tomography (SPET) in patients with temporal lobe epilepsy. Cerebral uptake of the
      muscarinic cholinergic antagonist [123I]4-iododexetimide (IDex) was investigated
      by SPET in patients suffering from temporal lobe epilepsy of unilateral (n=6) or
      predominantly unilateral (n=1) onset. Regions of interest were drawn on co
      registered magnetic resonance images. Hippocampal volume was determined in these
      regions and was used to correct the SPET results for partial volume effects. A
      ratio of hippocampal IDex binding on the affected side to that on the unaffected
      side was used to detect changes in muscarinic cholinergic receptor density.
      Before partial volume correction a decrease in hippocampal IDex binding on the
      focus side was found in each patient. After partial volume no convincing
      differences remained. Our results indicate that the reduction in hippocampal IDex
      binding in patients with epilepsy is due to a decrease in hippocampal volume
      rather than to a decrease in receptor concentration.

PMID- 9283111
TI  - Whole-body kinetics and dosimetry of L-3--123I-iodo-alpha-methyltyrosine.
AB  - The synthetic amino acid L-3--123I-iodo-alpha-methyltyrosine (IMT) is currently
      under clinical evaluation as a single-photon emission tomography (SPET) tracer of
      amino acid uptake in brain tumours. So far, dosimetric data in respect of IMT are
      not available. Therefore we investigated the whole-body distribution of IMT in
      six patients with cerebral gliomas and the radiation doses were estimated. Whole
      body scans were acquired at 1.5, 3 and 5 h after i.v. injection of 370-550 MBq
      IMT. The bladder was voided prior to each scan and the radioactivity excreted in
      the urine was measured. Based on the MIRD-11 method and the updated MIRDOSE3, the
      mean absorbed doses for various organs and the effective dose were calculated
      from geometric means of the anterior and posterior whole-body scans using seven
      source organs and the residence time. IMT was predominantly excreted by the
      kidneys (52.8%+/-11.5% at 1.5 h p.i., 63.0%+/-15.7% at 3 h p.i. and 74.6%+/-9.8%
      at 5 h p.i.). No organ system other than the urinary tract showed significant
      retention of the tracer. Early whole-body scans revealed slightly increased
      tracer uptake in the liver and in the bowel. Highest absorbed doses were found
      for the urinary bladder wall (0.047 mGy/MBq), the kidneys (0.010 mGy/MBq), the
      lower large intestinal wall (0.011 mGy/MBq) and the upper large intestinal wall
      (0.008 mGy/MBq). The effective dose according to ICRP 60 was estimated to be
      0.0073 mSv/MBq for adults. This leads to an effective dose of 3.65 mSv in a
      typical brain SPET study using 500 MBq IMT. The MIRDOSE3 scheme yielded similar
      results. Thus, in spite of the relatively high tracer dose required for optimal
      brain scanning, radiation exposure in SPET studies with IMT is in the normal
      range of routine nuclear medicine investigations.

PMID- 9283112
TI  - First experiences with technetium-99m furifosmin as tumour-seeking agent in
      breast cancer and recurrent ovarian cancer.
AB  - Recent in vitro studies suggest that technetium-99m furifosmin may have tumour
      seeking properties. We analysed the diagnostic value of 99mTc-furifosmin
      scintigraphy in nine patients with documented carcinoma of the breast and in
      eight patients with continued recurrent ovarian cancer. In the breast, 99mTc
      furifosmin failed to visualize the primary malignant tumour and the associated
      malignant lymph nodes in all patients. In contrast, multiple sites of increased
      tracer uptake were demonstrated in one patient with acute benign inflammatory
      breast disease. In four of eight patients with recurrent ovarian cancer, 99mTc
      furifosmin scintigraphy demonstrated early (5 min p.i.) localized increased
      uptake corresponding to adhesions to the bowel as diagnosed by computed
      tomography, but failed to reveal further abnormalities in all patients. The
      present study demonstrates that furifosmin is of no value in the imaging of
      breast cancer and recurrent ovarian cancer. These results do not continue the
      pattern observed in cell culture studies and are quite in contrast to the
      findings of mammoscintigraphy using 99mTc-methoxyisobutylisonitrile and 99mTc
      tetrofosmin.

PMID- 9283113
TI  - [123I]beta-CIT single-photon emission tomography in Parkinson's disease reveals a
      smaller decline in dopamine transporters with age than in controls.
AB  - In vivo studies using single-photon emission tomography (SPET) and positron
      emission tomography have shown an age-related decline in the number of striatal
      dopamine transporters in healthy subjects. We examined ten healthy subjects and
      33 de novo patients with Parkinson's disease (PD) using [123I]2beta-carbomethoxy
      3beta-(4-iodophenyl)tropane ([123I]beta-CIT) SPET. A clear age-related loss of
      dopamine transporters was found in the healthy subjects. In the PD group,
      controlling for the contribution of disease severity, we found a small (compared
      with controls) but significant decrease with aging, though only in the
      ipsilateral regions. This aging effect was especially pronounced in younger
      patients. We conclude that the use of age-correct SPET data in PD, based on
      studies with healthy subjects, may lead to an under- or an overestimation of the
      striatal binding measures.

PMID- 9283115
TI  - Frequency of adverse reactions to radiopharmaceuticals in Europe.
AB  - A prospective survey was performed in 17 nuclear medicine departments during 1996
      in an attempt to provide reliable data on the prevalence of adverse reactions to
      radiopharmaceuticals. All adverse events following radiopharmaceutical
      administration were recorded, irrespective of the severity or likelihood of
      causality, and subsequently analysed using an algorithm developed by Silberstein
      et al., designed to establish a cause-effect relationship. A prevalence of 11
      events per 10(5) administrations was obtained (95% confidence limits 3.3-19.2).
      No serious of life-threatening events were reported. This rate is slightly higher
      than that obtained in a larger scale study in the United States (2.3 events per
      10(5) administrations, 95% confidence limits 1.2-3.4). The difference may be due
      to the decision to include or exclude vasovagal events from the analysis, the way
      in which the algorithm was used and the comparative size and time scale of the
      two studies. The prevalence of adverse reactions is approximately 1000-fold than
      less that occurring with iodinated contrast media and drugs.

PMID- 9283114
TI  - The effect of chemotherapy on the uptake of technetium-99m sestamibi in breast
      cancer.
AB  - Technetium-99m sestamibi scintimammography has been used primarily in the
      diagnosis of breast cancer. It has also been suggested that this technique could
      be used to monitor response to chemotherapy and possibly to predict those
      patients in whom no response can be expected. An initial study was performed in
      nine patients with primary breast cancer. All patients underwent prone lateral
      and anterior 99mTc-sestamibi imaging at diagnosis and 4-7 months later, after
      they had received cytotoxic chemotherapy. The uptake of 99mTc-sestamibi in the
      breast was compared with that in normal surrounding breast tissue and this ratio
      was expressed as the target to background ratio. In all patients treated there
      was a reduction in uptake of 99mTc-sestamibi after treatment, such that whilst
      all the tumours could be seen before treatment, only three were visible following
      chemotherapy. There was a significant fall in the mean target to background ratio
      of the patients undergoing chemotherapy: the tumour to background ratio was 2.48
      before chemotherapy and 1.40 after treatment (P<0.001, paired Student's t test).
      This fall in tumour activity was observed both in those patients in whom a
      clinical response was seen and in the two patients in whom the tumour enlarged
      despite chemotherapy. It appears that the reduced uptake of 99mTc-sestamibi seen
      after chemotherapy may be a non-specific change and therefore may not be
      predictive of the clinical response to treatment.

PMID- 9283117
TI  - The author replies

PMID- 9283116
TI  - Radionuclide tracers in the evaluation of resting myocardial ischaemia and
      viability.
AB  - Of all the tracer techniques currently available for the detection of myocardial
      viability, it is the classic pattern of fluorine-18 deoxyglucose-perfusion
      mismatch that is clearest from the conceptual point of view and consistently
      gives good predictive values. Measurements of absolute rates of glucose uptake
      depend on the much criticized lumped constant, never validated for myocardial
      ischaemia, and may provide little additional information or may even be confusing
      because of the bi-directional changes in glucose uptake in response to increasing
      ischaemia. Labelled nitroimidazole compounds are currently of interest because
      they are "ischaemia-avid" and because they can be imaged by a gamma camera.
      Nevertheless, much more work is required to show whether retention of
      nitroimidazole in ischaemic tissue may reflect viability.

PMID- 9283118
TI  - Emerging food-borne diseases.

PMID- 9283119
TI  - Effect of marginal zinc deficiency on human growth and development.
AB  - Growth and development disorders in humans caused by zinc (Zn) deficiency have
      been investigated for a long time. Although marginal Zn deficiency is a common
      nutritional problem around the world, especially in the children of developing
      countries where diets have less Zn available, it is difficult to identify. This
      review provides the progression of studies in the effect of Zn deficiency on
      human growth and development, and also explains the possible mechanisms of how Zn
      promotes these phenomena. These mechanisms involve the effects of Zn on DNA
      synthesis, RNA synthesis, and cell division. The concept of zn-finger proteins
      explains the role of Zn in gene expression and endocrine function. Findings
      indicate that Zn deficiency can result in delayed growth and development which
      can be corrected in part by Zn supplementation.

PMID- 9283121
TI  - Anionic charge abnormalities of red blood cells and proteinuria in
      glomerulonephritides.
AB  - We studied alcian blue (AB) binding to red blood cells (RBC) [ABRBC] in 89
      children and adults with a variety of glomerular diseases. ABRBC was
      significantly reduced in the group as a whole when compared with healthy controls
      (P < 0.001). A moderate correlation between the degree of proteinuria and ABRBC
      was detected in the children with renal disease (r = 0.43, P < 0.001), but not in
      adult patients. A significant reduction in ABRBC was detected in 30 of the above
      children who had Steroid Responsive Nephrotic Syndrome (MCNS) compared to their
      controls (40.57 +/- 16.6 v. 75.09 +/- 7.81, P = 0.001). A similar decrease from
      normal values was observed in other childhood glomerular diseases: focal
      glomerulosclerosis, post-streptococcal glomerulonephritis, membranous nephropathy
      (52.31 +/- 26.07 v. 79.44 +/- 5.88, P = 0.001). Mean ABRBC was lower in MCNS than
      other histological groups (P = 0.0518). ABRBC was age-dependent (r = -0.399, P <
      0.02). These findings provide further indirect evidence of the relative roles of
      charge and size selective filters in glomerular basement membrane (GBM) in renal
      diseases, and suggest that depletion of anionic charge may be a major cause of
      proteinuria in MCNS.

PMID- 9283120
TI  - Clinical correlates of CT abnormality in generalized childhood epilepsy in India.
AB  - The CT scan gives valuable insight into the aetiology of epilepsy. Studies done
      so far in India suggest that the causes are quite different from the West. CT
      scan has become available in larger cities in India, but is expensive.
      Information about clinical features that may 'predict' a CT abnormality would be
      useful to clinicians. The object was to determine which, if any, of 10 clinical
      features predict a CT abnormality in patients presenting with generalized
      epilepsy. Consecutive children with generalized epilepsy were enrolled
      prospectively and clinical features charted. Predetermined clinical variables
      were compared in those with and without CT abnormality. The setting was a
      pediatric in-patients and out-patients of a teaching hospital in northern India.
      One-hundred-and-sixty-two out of 178 consecutive children (age 1 month to 12
      years) presenting with generalized epilepsy; ten clinical features viz seizure
      type, age at onset, number of seizures, duration of epilepsy, family/antecedent
      history, mental/neurological deficit, abnormal EEG and evidence of tuberculosis,
      were studied. Univariate analysis taking (1) CT abnormality/no abnormality and
      (2) ring/disc enhancing lesion/no such lesion on CT as outcomes. An abnormal CT
      scan was found in 79 (49 percent) patients. There were two high yield groups: (1)
      younger children with neurological/mental deficits; (2) older children without
      deficits. When these two groups were combined, odds ratio for CT abnormality was
      3.06 (1.4-6.7). The commonest CT abnormality was a ring/disc like enhancing
      lesion seen in 32 patients. Higher age at onset (> 4 years), absence of
      mental/neurological deficits, generalized tonic-clonic type of seizures and fewer
      episodes of seizures at presentation were significantly associated with this
      finding. In addition to existing indications for CT scan, these results can guide
      physicians when referring patients for this investigation.

PMID- 9283122
TI  - Immunodiagnoses of community-acquired pneumonia in childhood.
AB  - A diagnosis of bacterial pneumonia requires isolation of the pathogen from blood,
      lung or tracheal aspirate; however, cultures of blood and pleural fluid samples
      are usually insensitive. Thus, in the majority of patients the etiology is rarely
      determined. A total of 840 pleural fluid effusion samples from children with
      clinical and laboratory diagnoses of acute bacterial pneumonia were evaluated by
      Dot-ELISA. This method was standardized in order to detect polysaccharide
      capsular bacterial antigen in pleural fluid samples previously treated with 0.1 M
      EDTA and dotted on nitrocellulose membrane strips. Pneumococcal omniserum and H.
      influenzae type b antiserum diluted 1:200 were employed for detection of S.
      pneumoniae and H. influenzae type b antigens, respectively. Dot-ELISA showed
      relative indices of 0.913 for sensitivity and 0.552 for specificity, and a total
      positivity of 75.6 per cent, being 53.21 per cent for S. pneumoniae and of 22.38
      per cent for H. influenzae.

PMID- 9283124
TI  - Protein energy malnutrition and cerebral malaria in Nigerian children.
AB  - Eight (14 per cent) out of 57 consecutive cerebral malaria patients (all < 5
      years old) were malnourished, including one with marasmus and another recovering
      from kwashiorkor. This was significantly lower than among other paediatric
      patients in the same children's emergency ward (112/319, i.e. 35 per cent, P <
      0.01). Poor outcomes (death or recovery with neurological deficits) were commoner
      in the malnourished group (4/8) than the well nourished group (7/49) (P = 0.037,
      Fisher's exact test). Malnourished children should receive malaria
      chemoprophylaxis during nutritional rehabilitation.

PMID- 9283123
TI  - Relactation: an effective intervention to promote exclusive breastfeeding.
AB  - Fifty mothers of hospitalized infants less than 4 months old with partial or
      complete lactation failure (LF) were randomly assigned to two groups of 25 each
      for relactation. Majority of enrolled mothers (86 per cent) had complete LF and
      14 per cent had partial LF. Relactation was attempted in both the groups with
      motivation, support, and repeated suckling. Group II mothers, in addition, were
      given metoclopramide. The characteristics of mothers and babies, and socio
      economic background were comparable in both groups (P > 0.05). The primary
      outcome variables measured included the time of appearance of first breast milk
      secretion (in complete LF), time for partial and complete relactation.
      Relactation attempt was successful in 49 mothers (98 per cent), with complete
      relactation in 46 (92 per cent) and only partial relactation in three mothers (6
      per cent). Nipple confusion and frustration of the baby (4 per cent) in complete
      LF, small/retracted nipples (8 per cent), and sore/fissured nipples (4 per cent),
      which influenced the initiation of relactation, were overcome with drop and drip
      method, lact-aid support and proper positioning of the baby. All the outcome
      variables of the two groups were comparable (P > 0.05). The pattern of weight
      gain, the rate of reduction in the amount of top milk and subsequent weight gain
      in the follow-up was also comparable in both the groups (P > 0.05). Maternal
      factors like breast conditions, nutrition, parity, feeding practices in previous
      babies, lactation gap, and infants' initial refusal to suck at the breast did not
      influence the outcome variables as long as repeated suckling was ensured. We
      conclude that relactation is possible in most of the mothers without the help of
      lactagogues. Apart from educating and motivating the mother for exclusive
      breastfeeding during first 4-6 months, a strong professional support by a skilled
      health worker is needed to overcome the initial problems during relactation.

PMID- 9283125
TI  - Serum and urinary amino acid levels in sickle cell disease.
AB  - Neonates with sickle cell disease (SCD) are of normal size at birth in terms of
      height and weight. However, by the sixth month of life their growth begins to lag
      significantly behind that of non-sicklers. We hypothesize that such growth
      retardation could be explained, at least in part, by the increased excretion of
      free amino acids in the urine of children with SCD. It is well established that
      in SCD there are abnormalities in the proximal tubules where amino acids are
      reabsorbed. We collected serum and urine samples from 13 patients with SCD (age
      range, 10 months to 14 years), and 17 age-and gender-matched controls, and
      analysed these specimens for free amino acids and creatinine. The SCD population
      was less well nourished than the controls, as evidenced by the lower serum
      prealbumin levels in the former group (91.3 v. 127 mg/l, P = 0.01). The serum
      concentrations of all of the essential amino acids were significantly reduced (21
      47 per cent, P < 0.01) in the SCD subjects, as were those of most of the non
      essential amino acids (exceptions: alanine, glutamic acid, proline). The urine
      concentrations of seven of the essential amino acids (indexed to creatinine) were
      increased in the SCD children. The greatest difference in urinary amino acid
      excretion was seen with methionine; the SCD subjects excreted 3.6-fold more
      methionine than the controls. These data indicate that reduced levels of serum
      amino acids resulting from increased urinary loss of these amino acids in
      children with SCD could contribute to the decreased growth rates one sees in
      children with this genetically inherited hematologic disorder.

PMID- 9283126
TI  - Are there social inequities in child morbidity and mortality in rural Vietnam.
AB  - This study was conducted to investigate the relationship between various socio
      economic factors, and child morbidity and mortality during a period of rapid
      social change in Vietnam. One-thousand-one-hundred-and-thirty-two rural mothers
      with children under 5 years of age were interviewed regarding their reproductive
      history, survival of their children, and morbidity of their children under 5
      years of age. Causes of child death were established by a verbal autopsy
      technique. Fifty-seven per cent of the children were reported to have suffered
      from some illness during the preceding 2 weeks. Acute respiratory infection (ARI)
      (46 per cent of all children) was most common. Two-thirds of the sick children
      had been treated with antibiotics. Eighty-one children under 5 years of age had
      died during the 10-year period 1982-1992. Two-thirds of these deaths occurred in
      infancy, most of them were related to prematurity, asphyxia or tetanus. ARI was
      more common in poor families while neither education nor occupation were
      associated with ARI occurrence. No significant relationship between education or
      occupation of the mother and mortality was found. The low under-5 mortality
      (U5MR) in spite of the high morbidity may be related to good child health care
      both by families and by the health care system.

PMID- 9283127
TI  - Systemic and mucosal immune response to polio vaccination with additional dose in
      newborn period.
AB  - Administration of supplementary dose of oral polio vaccine (OPV) during neonatal
      period is recommended by WHO in countries like India, where host response to the
      regular to the regular three-dose schedule is not satisfactory and poliomyelitis
      continues to be a problem. The efficacy of this dose +3, and +5 doses of OPV in
      terms of seropositivity, seroconversion, systemic, and mucosal antibody responses
      were measured in 51 infants in a follow-up study from birth to 30 weeks.
      Administration of the additional dose in the newborn period significantly
      improved seropositivity and seroconversion rates compared to the conventional 3
      or 5 dose schedules. Systemic antibody titres improved with each dose of the
      vaccine and 40-60 per cent of infants had > 1:128 titres to the three types of
      polioviruses that could prevent re-infection of the gut and 50 per cent of them
      had mucosal antibodies as evidenced by specific IgA in nasopharyngeal secretions.
      Therefore, administration of OPV in the neonatal period should be made compulsory
      in countries where poliomyelitis still continues to be a problem.

PMID- 9283128
TI  - Breastfeeding and bloody diarrhoea in young children in Ibadan, Nigeria.

PMID- 9283129
TI  - Growth hormone secretion and serum insulin-like growth factor-I concentration in
      X-linked hypophosphatemic rickets before and after treatment.
AB  - The aetiology of growth retardation in children with X-linked hypophosphatemic
      rickets (HPR) has not been totally defined. We evaluated growth hormone
      (GH)/insulin-like growth factor-I (IGF-I) changes in relation to linear growth
      and biochemical parameters in seven children with X-linked hypophosphatemic
      rickets before and after treatment with 1,25-dihydroxyvitaminD3 and phosphate
      therapy for a year or more. Moreover, we compared patients' growth data and
      GH/IGF-I changes with those for 20 age-matched children with normal variant short
      stature (NVSS)[with normal GH secretion and height standard deviation score
      (HtSDS) before -2]. Before treatment, all children with HPR secreted normal GH in
      response to clonidine provocation (> 10 microgram/l) and their IGF-I
      concentration was significantly lower than those with NVSS. The HtSDS and growth
      velocity (GV) of children with HPR improved significantly after (-3.05, 8.9
      cm/year, respectively) v. before (-3.9 and 4.1 cm/year, respectively) therapy.
      Their serum IGF-I concentration increased significantly from 76.7 ng/ml before to
      99.6 ng/ml after treatment. In summary children with HPR had no abnormality of GH
      secretion but improvement of their linear growth was associated with significant
      increase of circulating IGF-I concentration after treatment.

PMID- 9283131
TI  - Blood pressure measurement in children aged 7-15 years in Sivas region-Turkiye.

PMID- 9283133
TI  - Use of local cost effective diets in the management of persistent diarrhoea.

PMID- 9283132
TI  - Deaths in childhood nephrotic syndrome in Ibadan, Nigeria.

PMID- 9283130
TI  - Calcitonin therapy in vitamin D intoxication.

PMID- 9283134
TI  - News from the regions--newsletter from Italy.

PMID- 9283136
TI  - [Rapid identification of Bilophila wadsworthia].
AB  - Biophila wadsworthia is a recently recognized nonspore-forming anaerobic gram
      negative rod and is reported to be associated with various infections such as
      gangrenous perforated appendicitis, peritonitis, osteomyelitis and bacteremia.
      Although the isolation of B. wadsworthia seems to be facilitated by using
      Bacteroides bile esculin (BBE) agar, the reliable scheme of identification of
      this species has been published. This study was conducted to find simple, rapid,
      and reliable measures for identification of B. wadsworthia. A total of 32 B.
      wadsworthia-suspected clinical isolates as well as B. wadsworthia WAL 7959 and
      Desulfomonas pigra DSM 749, which is the species that shows bacteriological
      characteristics similar to B. wadsworthia, were used. Through the study of
      various biochemical and enzymatic tests and culture on selective media, it is
      indicated that a nonspore-forming, gram-negative anaerobic rod that is nonmotile,
      forms "black-eyed" colonies on BBE agar, and demonstrates strongly positive
      catalase test, positive acid phosphatase test, and no-growth on Bacterides medium
      or to be susceptible to colistin (10 micrograms disk) can be identified as B.
      wadsworthia.

PMID- 9283135
TI  - Genetic analysis of Pseudomonas aeruginosa by pulsed field gel electrophoresis.
AB  - We identified the serotypes and genomes patterns of 100 strains of Pseudomonas
      aeruginosa (P. aeruginosa) that had been isolated from patients who were admitted
      to the hospital of the Fukui Medical School between 1992 and 1995. A monoclonal
      diagnostic kit was used to identify the serotypes. Genome patterns were
      determined by pulsed field gel electrophoresis (PFGE). Serotypes A, B, C, D, E,
      F, G and I exhibited distinct genome patterns. Differences in genome patterns
      were also observed in strains of serotypes E and G, depending on the types of
      clinical samples collected and/or the area of the hospital from which they were
      isolated. Many of the multiple antibiotic-resistant strains of P. aeruginosa
      exhibited serotype E. The genome pattern differed between strains that were
      susceptible vs. resistant to multiple antibiotics. The latter strains exhibited
      similar genome patterns regardless of their origin. These findings suggest that
      analysis of genome patterns is important for identifying the origin of nosocomial
      infection caused by P. aeruginosa, serotype E.

PMID- 9283137
TI  - [Genotyping of clinical isolates of MRSA by PFGE and AP-PCR].
AB  - Genotyping of 67 clinical isolates of methicillin-resistant Staphylococcus aureus
      (MRSA) separated from patients in a hospital in Mizusawa City in 1994 and 1995
      was studied by pulsed field gel electrophoresis (PFGE) and arbitrarily primed
      polymerase chain reaction (AP-PCR). Two main genotypes were observed by PFGE, and
      more than 70% of the 67 MRSA isolates produced coagulase type II. One group
      diverged well and gained higher tolerance in 1994, but was not isolated in 1995.
      The other group was continually isolated during the two-year period and showed
      moderate tolerance in 1994, and higher tolerance in 1995. AP-PCR was able to
      classify the genotypes of MRSA into 6 subgenotypes under the present conditions,
      which supported the results obtained by PFGE. These results suggest that AP-PCR
      could become a convenient and useful typing method by improving both sequence and
      length of a primer.

PMID- 9283138
TI  - [Trial for isolation of Helicobacter pylori form fecal specimen by immunomagnetic
      beads separation].
AB  - In order to clarify the possibility of feco-oral transmission of Helicobacter
      pylori, we have employed an immunomagnetic beads (IMB) separation technique and
      tried to isolate H. pylori from fecal samples. Microaerophilic cultivation and
      PCR of H. pylori were positive when H. pylori (10(3) cfu) was suspended in Hanks'
      balanced salt solution (HBSS) for the IMB separation technique. In contrast, when
      a lower number of H. pylori (10(2) cfu) was suspended in HBSS, 2nd PCR was
      positive but cultivation was negative. After IMB separation technique from fecal
      sample containing H. pylori (2 x 10(4) cfu), 20 cfu of H. pylori was recovered by
      culture. In this case, 1st PCR was negative but 2nd PCR was positive. From a
      fecal sample of a patient infected with H. pylori, H. pylori was detected only by
      combination of IMB separation and PCR, although H. pylori was not recovered by
      culture. These results indicate that IMB separation technique followed by
      cultivation or PCR would be useful for estimation of the presence of H. pylori
      fecal samples.

PMID- 9283139
TI  - [Clinical and diagnostic characteristics of Legionella pneumonia].
AB  - We have characterized clinical and diagnostic features in 18 cases of Legionella
      pneumonia. Age average of patients was 62.0 years old (male:female = 14:4) and
      underlying diseases were observed in 12 patients. Legionella pneumonia were
      diagnosed in 3, 5, 8 and 9 cases by culture, serum antibody measurement, urinary
      antigen detection and PCR, respectively. Sixteen cases were caused by L.
      pneumophila, while the other 2 cases were L. bozemanii pneumonia and L.
      pneumophila or L. dumoffii pneumonia. Chest X-rays of those patients showed
      multiple pneumonia shadows in 14 cases, alveolar shadows in 10 cases, pleural
      effusion in 5 cases. Blood-gas analysis on admission indicated hypoxemia in all
      cases with abnormal A-a DO2. Laboratory findings showed abnormal data in WBC,
      CRP, LDH, CPK and liver function tests (ex. GOT, GPT) in most cases. Serum
      antibody testing showed positive by 5 weeks after onset of pneumonia, but 10
      cases of Legionella pneumonia diagnosed by other techniques were judged to be
      negative. In urinary antigen detection test, 6 and 2 cases showed positive 1 and
      4 weeks after onset of pneumonia, respectively. Macrolide antibiotics were
      administered in all cases during the episode, but delay of macrolide
      administration was observed in 3 of 4 cases of dead outcome. Serum antibody
      measurement, urinary antigen detection and PCR, in addition to culture to
      bacteria, may be required for exact diagnosis of Legionella infection.

PMID- 9283140
TI  - [Bacteriological studies on sporadic diarrhea diseases in Oita District, 1985
      1996].
AB  - Approaching the problem of how close the sporadic diarrhea diseases correlate
      with epidemics of infectious diarrheas, including food poisonings,
      bacteriological studies were made on the characteristics of sporadic diarrheas in
      the past 10 years and analyzed. In collaboration with physicians, mostly
      pediatricians, in Oita district during 1985 to 1986 and 1989 to 1996, a total of
      1707 specimens was obtained from diarrhea patients, suspected of bacterial cause.
      We have isolated 717 strains from 670 specimens (ca 40% of the total). The
      majority were; Campylobacter, Salmonella and EPEC with the rate of about 40, 24
      and 23% respectively. On the other hand, isolation of Vibrio spp. and
      Staphylococcus were very few. The yearly trend of detection rates of such major
      agents were as follows: Campylobacter had the highest rate in the early period,
      1989, but thereafter tended to decrease. In contrast, Salmonella continued to
      increase in rate through the study period until the present when it exceeds that
      of Campylobacter. This alternation is due primarily to the rapid increase of S.
      Enteritidis since its recent appearance. VTEC stays at a low rate with a slow
      increase showing no prevalence so far. From the above results the following may
      meet with attention. Vibrios and Staphylococci, known as popular agents for food
      poisonings, seem unlikely to correlate with sporadic diarrheas. Instead, the
      evidence that recent food poisoning is often represented by Salmonella,
      especially S. Enteritidis, suggests that epidemics of infectious diarrhea may be
      attributed to the background of common sporadic diarrheas.

PMID- 9283141
TI  - [Colonization types of Escherichia coli in experimental urinary tract infection
      in compromised mice treated with hydrocortisone].
AB  - We studied the experimental urinary tract infections (UTIs) on compromised mice
      with Escherichia coli to elucidate the effects of three factors (bacterial
      strains, doses of hydrocortisone, infectious periods) on the bacterial
      colonization in the bladders. We selected three strains from the stock of E. coli
      isolated from the urine or feces of patients with lower UTI, because each of the
      three strains showed a tendency in colonization in previous experiments: One
      strain, which was named H70, showed a relative slight and intracellular
      colonization; the H99, an extracellular and the K88, both intracellular and
      extracellular growths which were large. The rate of bacterial microscopic
      recovery from the bladders of mice inoculated strains H70, H99 and K88 were 25.0,
      41.7 and 79.2% respectively. And the recovery from the mice inoculated cortisone,
      0, 2, 4 and 8 mg/mouse were 38.9, 55.6, 55.6 and 44.4% respectively. The
      detections of various colonizations at 3, 6 and 24 hr after the bacterial
      inoculation were that extracellular types were 45.8, 20.8 and 20.8%,
      intracellular types were 4.2, 16.7 and 12.5%, simultaneous colonizations were
      4.2, 16.7 and 4.2% and the detections of at least one of them were 54.2, 54.2 and
      37.5% respectively. Thus, the global findings were that extracellular growth of
      the bacteria were predominant at first, then the bacteria invaded the mucosal
      cells and the intracellular bacteria stayed after the voiding of extracellular
      bacteria. Intracellular colonizations seemed more strongly interacting with hosts
      than extracellular types, because cortisone enhanced the intracellular
      colonizations more strongly than the others. However, it seemed that urinary
      tract infections were not simple events but the results of the interactions of
      the bacterial strains and hosts, because the locations and degrees of the
      bacterial colonization and the effects of hydrocortisone on them were different
      in each bacterial strain and infectious period.

PMID- 9283142
TI  - [Effects of globulin preparations on phagocytic killing of oral streptococci].
AB  - The phagocytic bacterial activity on Streptococcus intermedius and Streptococcus
      oralis, clinical isolates from patients suffering from severe oral surgical
      infections, was evaluated by using sera and neutrophils of patients who had been
      treated with polyethylene glycal treated human normal immunoglobulin
      (Venoglobulin-IH). The phagocytic function of the neutrophils against the two
      strains, approximately 10 cells/neutrophil, was unrelated to the administration
      of Venoglobulin-IH. The bactericidal function of the serum and neutrophils on the
      third day following Venoglobulin-IH administration, on the other hand, rose to 10
      times that of the sera and neutrophils of patients with mild infections. The
      agglutinin titer of Venoglobulin-IH against S. intermedius and S. oralis were 32
      and 16 times, respectively, indicating an evident rise in these titers against
      the clinical isolates in comparison with the reference strains of the same
      organisms. These findings indicated that the oral streptococci that are isolated
      from patients with grave infections are associated with an antigenicity that is
      different from the normal bacterial flora; and these organisms are more labile to
      phagocytosis by neutrophils that were obtained from patients who have been
      treated with Venoglobulin-IH.

PMID- 9283144
TI  - [An autopsy case of chronic granulomatous disease diagnosed by biopsy].
AB  - This report concerns a male patient aged 25 years, diagnosed at the age of 12
      years as suffering from chronic granulomatous disease. This patient had p47-phox
      deficiency. He was admitted to this hospital because of fever and dyspnea
      accompanied by right spontaneous pneumothorax. He failed to respond to medical
      treatment. He died from respiratory failure four months after admission. Autopsy
      demonstrated pigmented lipid histiocytes characteristic of CGD. These
      characteristic pigmented cells were distributed in the spleen, liver, lymph nodes
      and in the small intestine. As for the nature of the pigment, lipofuschin-like
      compound were identified. Granulomatous component was seen in the mucosa of the
      stomach obtained by operation. The presence and characteristic distribution of
      such pigmented macrophages in tissue in young adults may suggest the diagnosis of
      CGD.

PMID- 9283143
TI  - [Detection of intestinal parasites from main-land raccoon dogs, Nyctereutes
      procyonoides viverrinus, in southeastern Kanagawa Prefecture].
AB  - To obtain the basic data on the route of infection of intestinal parasites as
      zoonosis, we examined the feces from 87 main-land raccoon dogs, all of which were
      kept in the Yokohama Kanazawa Zoo (Kanagawa) between 1994-1996, for detection of
      intestinal parasites and evaluated the detection rates. Intestinal parasites were
      detected from 72 of the 87 raccoon dogs (82.8%). Among the parasites, Ancylostoma
      spp., Trichuris vulpis, Ascaridoidea and Isospora spp. were most commonly
      detected. Of the 72 raccoon dogs with parasites, 43 (59.7%) had mixed infection
      of more than two species of parasites. Since Ancylostoma spp., Ascaridoidea and
      Isospora spp., which are important causes of human diseases, were detected at
      relatively high rates, it was suggested that the raccoon dog could be a source of
      human infection of intestinal parasites.

PMID- 9283145
TI  - Schistosomiasis haematobium--a case imported by a Japanese patient.

PMID- 9283146
TI  - [Prosthetic endocarditis caused by Kingella denitrificans in a patient with
      diabetes mellitus].
AB  - Infective endocarditis caused by Kingella denitrificans occurs rarely. A review
      of the literature reveals only 6 cases of endocarditis caused by the bacillus. K.
      denitrificans is normally a commensal of the upper respiratory airways, may
      exceptionally be responsible for endocarditis. A case of possible prosthetic
      endocarditis caused by K. denitrificans is presented. A 78-year-old male with
      Type II diabetes was admitted to the hospital complaining of fever, a sore throat
      and arthralgia. He underwent replacement surgery of a St. Jude medical prosthesis
      for aortic stenosis at the age of 75. The only physical findings at admission
      were a temperature of 38.2 degrees C and murmurs of mild mitral regurgitation.
      The liver and spleen were not palpable, and there were no skin or eye lesions.
      Laboratory findings were as follows: white blood cell count 9500/microliters with
      77% neutrophils, erythrocyte sedimentation rate 71 mm/h (Westergren), blood urea
      nitrogen 50.2 mg/dl, serum creatinine 1.7 mg/dl and C-reactive protein 22.2
      mg/dl. The Gram-negative bacillus isolated from the blood was identified as K.
      denitrificans by the identification system, namely ID test.FN-20 rapid (Nissui,
      Japan). Although an echocardiogram detected no vegetation, infective endocarditis
      was diagnosed because the same bacillus was detected by separate blood cultures
      and an obvious source of infection was not found other than the prosthetic valve.
      Initial treatment was flomoxef, which was changed to Ampicillin 2 g/day after K.
      denitrificans was identified. Ampicillin continued for 6 weeks. The clinical
      course was good and he did not require further surgery. He has been afebrile for
      2 years after completing treatment. This case represents the first report of
      prosthetic valve endocarditis caused by K. denitrificans in Japan.

PMID- 9283148
TI  - Short-term change of optic nerve head topography after trabeculectomy in adult
      glaucoma patients as measured by Heidelberg retina tomograph.
AB  - Using Heidelberg Retina Tomograph (HRT, Heidelberg Engineering, Heidelberg,
      Germany) we investigated whether reversal of glaucomatous optic disc cupping
      occurs in adult glaucoma patients following intraocular pressure (IOP) reduction
      by trabeculectomy, and whether topographic change in the optic disc differs
      according to region. Thirteen eyes of 13 glaucoma patients in whom IOP reduction
      was 25% or more at postoperative follow-up of 2 months were enrolled in the
      study. Cup/disc area ratio had decreased significantly, while rim area and rim
      volume showed significant increases (p < 0.05, Wilcoxon signed rank test). Among
      the optic disc sectors, rim area in the superior and inferior quadrants,
      especially in the superotemporal and inferotemporal octant, had increased
      significantly. The decrease in maximum cup death correlated significantly with
      the recent IOP reduction (r = 0.698, p = 0.016). Reversal of glaucomatous disc
      cupping after IOP reduction following trabeculectomy in adult patients as
      confirmed by HRT. Furthermore, the regions of selective reversal in the superior
      and inferior quadrants coincided with those parts of the optic nerve head in
      which early functional and structural glaucomatous damage has been known to
      occur.

PMID- 9283147
TI  - [A case of bacterial meningitis induced by strongyloidiasis].
AB  - A 75-year-old female with diabetes mellitus, who was born and lived in West north
      Kyusyu, was admitted to our hospital, because of unconsciousness and loss of
      appetite. The physical examination showed neck stiffness and a high fever. The
      laboratory data showed accentuation of inflammatory reaction and azotemia and
      positive HTLV-1 antibody. The spinal fluid showed increase of cell count and
      amount of protein. A stool and sputum smear revealed rhabditis form larvae of the
      nematode. Antibiotics and ivermectin were administered for the bacterial
      meningitis and hyperinfection of the strongyloides, respectively. Consequently,
      meningitis and strongyloidiasis improved. It was considered that the patient was
      infected with strongyloides from her husband who serve in the army during World
      War II, and hyperinfection of strongyloides resulted from the immunosuppressive
      state of diabetes mellitus. Ivermectin, and anti-strongyloides agent, was
      effective, and no side effects were seen. However, the therapeutic resistance in
      this case was associated with the positive HTLV-1 antibody.

PMID- 9283149
TI  - Circumferential profiles of peripapillary surface height with confocal scanning
      laser ophthalmoscopy.
AB  - The purpose of this study was to compare the circumferential profiles of relative
      peripapillary retinal surface height (RPSH) between normal and glaucoma, with a
      confocal scanning laser ophthalmology (CSLO), and to examine the ability of the
      mean height to distinguish glaucoma from normal. Fifty-three patients with open
      angle glaucoma and forty-three normal subjects matched for age, race and
      refractive error were studied. To extract circumferential profiles, we developed
      software to quantify RPSH from images obtained with a CSLO (Heidelberg Retina
      Tomograph (HRT), Heidelberg Engineering, Germany, Software: IR1-V1.11) outside
      the optic disc margin every 50 microns. Mean heights from circumferential
      profiles were calculated and compared between normal and glaucoma. Receiver
      operating characteristic (ROC) curves were used to evaluate sensitivity and
      specificity of the mean height to discriminate normal from glaucoma subjects. T
      he average (+/- SD) visual field mean deviation in the glaucoma group was -4.8 +/
      3.4dB. The average height of each circumference increased from the disc margin
      to 250 microns away in both normal and glaucoma subjects. There were
      statistically significant differences for the mean height (P < 0.001) between the
      two groups. The largest difference between normal and glaucoma was found in the
      inferior sector compared with the other sectors (p < 0.001). The sensitivity,
      specificity and diagnostic precision of the mean height were 83%, 67% and 76%,
      respectively. The mean height from the circumferential profiles of RPSH can be
      used as a useful marker to identify early glaucoma.

PMID- 9283150
TI  - Management of chronic hypotony following trabeculectomy with mitomycin C.
AB  - Chronic hypotony is marked by decreased vision and late-onset leaking bleb after
      filtration surgery using topical mitomycin C; to manage this condition we
      followed a three-step approach: first, intrableb autologous blood injection;
      second, surgical exploration and additional suturing of the scleral flap; third,
      excision of the cystic bleb and advancement of a fornical conjunctival flap. For
      the avascular flap cystic blebs of five patients. In three of the six eyes, there
      was no increase of intraocular pressure (IOP); two eyes showed massive hyphema
      and were mildly resistant to the injection of autologous blood, and in one, a
      leaking hole was seen in the bleb wall two days after the injection of blood. Two
      eyes of three in which blood injection had failed, and another, in which the bleb
      had spread over more than half the eyeball, and which was the patient's only
      sighted eye, underwent the second step of the procedure. The remaining leaking
      eye, in which blood injection had been complicated, and another, in which
      spontaneous leakage from a thin avascular bleb had occurred, were subjected to
      the third step. After each of the three approaches, IOP increased on average from
      1.67 to 5.67 mmHg, from 2.33 to 11.33 mmHg, and from 1.5 to 7 mmHg, respectively;
      each approach successfully improved vision. Intrableb autologous blood injection
      is a simple procedure for the management of chronic overfiltration and a way of
      determining whether excessive filtration is occurring through the scleral flap,
      in which case additional suturing is required, or in another way. Depending on
      the status of the bleb, additional suturing or excision of the cystic bleb and
      advancement of the fornical conjunctival flap are useful modalities for the
      treatment of late-onset leaking filtration bleb.

PMID- 9283151
TI  - Conjunctival impression cytology of the filtering bleb.
AB  - Impression cytology was used to evaluate the conjunctival surface change after
      filtering surgery and its association with bleb type and mitomycin C. Impression
      cytology were obtained at least ten (mean, 20.4) months after surgery from 22
      eyes of 19 patients who had undergone trabeculectomy, and were graded according
      to a previously described system. Blebs were divided into thin cystic and thick
      diffuse types. Abnormal impressions, demonstrated as disturbed epithelial and
      goblet cell morphology and a decrease in the numbers of both cells, were found in
      nine eyes (40.9%). With regard to the prevalence of abnormal impressions, there
      were statistically significant differences between bleb type and between the use
      or non-use of mitomycin C (p = 0.040, 0.013); these related more to the use of
      mitomycin C than to bleb type. This study reveals that filtering surgery causes
      long-term damage to the conjunctival epithelium overlying a filtering bleb,
      especially in a patient with a thin cystic bleb or one has been treated with
      mitomycin C. This change in the conjunctival surface may lead to the occurrence
      of late hypotony and bleb-related infection.

PMID- 9283152
TI  - The effect of growth factor on antigen and viability of corneal endothelial
      cells.
AB  - The effect of epidermal growth factor (EGF) on corneal endothelial cell of
      rabbit, was evaluated. DNA synthesis of cultured corneal endothelial cells after
      adding EGF to culture medium and major histocompatibility (MHC) antigen
      expression of cornea preserved in EGF added Optisol were measured. EGF increased
      DNA synthesis of corneal endothelial cells at all concentrations tested (0.03
      ng/ml-300 ng/ml) compared with control. The maximum increase of DNA synthesis was
      shown at the concentrations of 3.0-30 ng/ml. The effect of EGF on increase of DNA
      synthesis was more profound in second sub-cultured cells compared with first sub
      cultured cells. In corneas preserved in Optisol for 3 days, 4 degrees C, class I
      antigen expression is decreased while class II antigen expression was slightly
      increased. In corneas preserved in EGF added Optisol for 3 days, 4 degrees C,
      class II antigen expression was more increased compared with those without EGF.

PMID- 9283153
TI  - Species identification and molecular characterization of Acanthamoeba isolated
      from contact lens paraphernalia.
AB  - We applied ribosomal RNA gene (rDNA) polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) to identify Acanthamoeba isolates from
      contact lens paraphernalia, and characterized these on the basis of mitochondrial
      DNA (mtDNA) RFLP and isoenzyme analysis. The 22 Acanthamoeba strains used as
      reference strains were obtained from the American Type Culture Collection. Twenty
      eight isolates were classified into six ribogroups, as follows: Acanthamoeba
      ribogroup (AcRG) 1 consisted of 18 isolates; AcRG 2, of three, AcRG 3, of three;
      AcRG 4, of two; AcRG 5, of one, and AcRG 6, of one. AcRG 1, which was the most
      frequently isolated type, was identified as A. lugdunensis, and AcRG 2 as A.
      hatchetti. AcRG 4 was identified as A. triangularis, while AcRG 3 and AcRG 5 were
      closely related to A. triangularis. AcRG 6 was identified as A. castellanii. The
      mtDNA RFLP patterns and zymograms for five isoenzymes of the isolates belonging
      to a ribogroup were identical to one another. The mtDNA digestion phenotype and
      zymogram for acid phosphatase (AcP) of AcRG 1 were identical to those of A.
      lugdunensis L3a and KA/E2, the type strain and corneal isolates from a Korean
      keratitis patient, respectively. The mtDNA digestion phenotype and zymogram for
      AcP of AcRG 6 were identical to those of A. castellanii Castellani and KA/E3, the
      type strain and another corneal isolate found in Korea, respectively. The mtDNA
      RFLP and zymogram for AcP of AcRG 2 were very similar to those of A. hatchetti BH
      2 and Chang, respectively the type strain and a pathogen. The mtDNA RFLP and
      zymogram for AcP of AcRG 4 were similar to those of A. triangularis SH621, the
      type strain. The mtDNA RFLP patterns of AcRG 3 and 5 were unique. These results
      showed that the riboprints, mtDNA RFLP and zymograms of 22 of 28 Acanthamoeba
      isolates were the same as or very similar to those of the clinical isolates,
      which can probably be regarded as keratopathogens. More attention should be paid
      to the prevention of contamination by Acanthamoeba and to the disinfection of
      contact lens paraphernalia.

PMID- 9283154
TI  - The inflammatory potential of surgical glove lubricants: Biosorb, Keoflo, calcium
      carbonate and Hydrocote after intravitreal injection.
AB  - Surgical glove powders have been implicated in serious postoperative foreign body
      reactions due to contamination of the operative field. Inflammatory responses to
      glove lubricants or mold release agents have to date been studied to a lesser
      extent in ocular tissues than other body tissues, although powder contamination
      of intraocular lenses, with severe postoperative anterior chamber inflammatory
      responses, have been reported. The object of this study was to grade and
      quantitate the inflammatory response of surgical glove lubricants, namely
      Biosorb, Keoflo, calcium carbonate and Hydrocote (a hydrogel polymer film used in
      powderless gloves), as introduced into the posterior chamber on New Zealand white
      rabbits. In a double masked GLP study, a total of 150 eyes were evaluated. For
      each of the four test samples, a dose response curve was obtained at 10
      micrograms (Keoflo only), 125 micrograms, 250 micrograms, 500 micrograms, 1000
      micrograms, and 1500 micrograms. Study parameters were the quantitation of
      inflammatory cells in the aqueous and vitreous, and ocular irritation and
      inflammation, as graded by the rabbit inflammation score system, at 0 and 48
      hours post-injection. A Wilcoxen signed-rank test used to evaluate statistical
      significance (p < 0.05). A test vitreal cell count was less that 50 cells/mm3 and
      the overall mean clinical response was less than 2.0. This study established that
      Keoflo at all concentrations 10 micrograms-1000 micrograms), and Biosorb at
      concentrations greater than 1000 micrograms were inflammatory. Calcium carbonate
      and Hydrocote were non-inflammatory at concentration of 125 micrograms-1500
      micrograms. The unoperated, sham, vehicle and Ocugel controls were all non
      inflammatory. The positive Zymozan A controls were defined as inflammatory. In
      conclusion, no glove powder is totally safe, even small amounts of glove powder
      (10 micrograms) can elicit an inflammatory immune response. If all glove powder
      averages 700mg/pair, this should be removed prior to contact with a patients
      tissue. Powder-free gloves and greatly reduce the potential inflammatory risk
      associated with powdered gloves.

PMID- 9283155
TI  - Preretinal neovascularization induced by experimental retinal vein occlusion in
      albino rats.
AB  - Retinal ischemia and neovascularization have been demonstrated in several animal
      models. To determine 1) whether the retinal or preretinal neovascularization can
      be induced in albino rats by retinal vein occlusion and 2) the type and rate of
      occurrence on neovascularization, we occluded retinal veins in albino rats by
      photodynamic thrombosis. After anesthesia, each of 36 rats received an injection
      of rose bengal photosensitive dye, and their veins underwent argon green laser
      treatment. Half or all the major retinal veins were occluded in 12 eyes and in 24
      eyes, respectively. Ten control rats underwent the same procedures but the laser
      beam was directed between major retinal vessels. In 46 control eyes, rose bengal
      dye was seen to have perfused without laser treatment. Retinal detachment
      developed in most vein occluded eyes within one day of venous occlusion, which
      was confirmed by fluorescein angiography. On follow-up at two weeks, only four of
      24 eyes (16.7%) had undergone occlusion of all retinal veins showed new
      preretinal vessels on the optic disc. In these four eyes, severe disturbance of
      both retinal arterial and venous blood flow was observed, but no other eyes
      showed such severe combined disturbance. These data suggest that preretinal
      neovascularization in albino rats can be induced by this minimally traumatic
      method and that venous occlusion is severe enough to compromise arterial blood
      flow for a certain threshold period, thus inducing the development of preretinal
      neovascularization.

PMID- 9283156
TI  - Four cases of dacryocystocele.
AB  - Dacryocystocele is a rare complication of chronic dacryocystitis. We report four
      such cases in which epiphora and painless cystic mass located inferior to the
      medical canthus were manifested. Computed tomographic scanning of the orbit
      showed a well-demarcated low density mass in the lacrimal sac area, and extending
      to the nasolacrimal duct. We completely or partially excised the mass and
      depending on the condition of the canaliculi and puncta, performed
      dacryocystorhinostomy, canaliculorhinostomy, or conjunctivodacryocystorhinostomy
      using Jones' tube. Operative findings revealed that the lacrimal sac and
      nasolacrimal duct were dilated with obliterated proximal and distal portions the
      cyst. When cysts in the lacrimal sac area develop subsequent to chronic epiphora
      or are accompanied by punctal agenesis, differential diagnosis should consider
      the possibility of dacryocystocele.

PMID- 9283158
TI  - [Evaluation of atherosclerotic changes in the thoracic aorta using
      transesophageal and epiaorta echocardiographies in patients undergoing coronary
      artery bypass graft].
AB  - The aim of this study was to evaluate the atherosclerotic changes of the entire
      thoracic aorta using transesophageal echocardiography (TEE) as well as epiaorta
      echography (epiaorta echo) in CABG surgical patients and to evaluate specifically
      the use of epiaorta echo. A total of 230 consecutive patients were studied (201
      TEE, and 29 both TEE and epiaorta echo examinations). Intra-aortic plaque was
      detected by 70.0 +/- 8.5 years, while that of 73 patients without plaque was 54.5
      +/- 9.2 years. The difference was statistically significant (P < 0.001). The
      plaque was detected as solitary or diffused. By TEE, it was impossible to obtain
      images from the distal ascending aorta to the proximal aortic arch (blind zone).
      By epiaorta echo, clear images from the aortic valve annulus to the first 3 cm of
      proximal ascending aorta was difficult to obtain. However, the rest of the
      ascending aorta to the proximal arch was clearly imaged. Thus, when TEE
      demonstrates diffused plaque in the aortic annulus to the proximal ascending
      aorta, epiaorta echo should be used to examine the distal ascending aorta to the
      proximal arch.

PMID- 9283159
TI  - [Changes in symptom and thermography images after lumbar sympathetic ganglion
      block].
AB  - In 35 lower limbs of 22 patients with peripheral circulation disturbance, we
      evaluated the effects of lumbar sympathetic ganglion block (LSGB) by skin
      temperature difference (delta T) between the two measured by thermography before
      and after LSGB. We divided the patients into two groups; ASO group (n = 15):
      patients with chronic arterial occulusive diseases, and nonASO group (n = 7):
      those with peripheral circulation disturbance partly due to decrease nervous
      function. After LSGB, we recognized a significant increase in delta T and
      remission of ischemic symptoms in all the patients of nonASO group and those in
      early stage of ASO group. This suggests that in ASO group LSGB should be applied
      as soon as possible to obtain good outcome, and thermography is useful to
      evaluate the effects of LSGB in patients with peripheral circulation disturbance
      of the lower limbs.

PMID- 9283157
TI  - Dapsone maculopathy.
AB  - After the injection of about 10 gm of dapsone, a 38-year-old male showed a
      whitish-yellow patch in the macular region of both eyes, with decreased visual
      acuity of the counting finger in the right and 0.04 in the left eye. Two weeks
      after the start of systemic steroid therapy the patch disappeared, and on follow
      up at 11 months, visual acuity was 0.02 in the right and 0.08 in the left eye,
      with macular degeneration and foveal nonperfusion. This retinal damage seems to
      be ischemic in origin and to be caused by a combination of acute severe
      peripheral hypoxemia and the vascular obstructive effect of red cell
      fragmentation resulting from massive hemolysis.

PMID- 9283160
TI  - [Effects of loprinone hydrochloride on hemodynamics and respiratory oxygenation
      in patients after cardiac surgery].
AB  - Loprinone hydrochloride (Lop), a phosphodiesterase fraction III inhibitor and
      positive inotrope, was recently released in Japan. We evaluated its dose-related
      effects on hemodynamics and oxygenation as as well as on plasma levels of Lop in
      ten patients after cardiac surgery. Immediately after admission to the intensive
      care unit, baseline hemodynamics and arterial blood gas data were obtained;
      patients with inotropic support, were given 0.1, 0.2, 0.3 microgram.kg-1.min
      1.lop over 1 hour incrementally, and additional data were obtained. CI increased
      significantly from baseline (2.1 +/- 0.3 l.min-1.m-2) to 3.2 +/- 0.8 at 0.3
      microgram.kg-1.min-1. Systemic vascular resistance decreased significantly from
      baseline (2853 +/- 439 dynes.sec.cm-5.m-2) to 1554 +/- 440 at 0.3 micrograms. kg
      1.min-1, and mean arterial pressure also decreased significantly from baseline.
      There were no significant changes in heart rate (HR), central venous pressure
      (CVP), pulmonary artery occlusion pressure (PAOP), or PaO2.FIO2(-1) in patients
      over the period evaluated. Plasma levels of Lop rapidly increased to 27.8 ng.ml-1
      (effective level; 20 ng.ml-1) at 0.3 microgram.kg-1.min-1. In this study, Lop was
      shown to effectively increase CI in patients after cardiac surgery with no
      significant changes in HR, CVP, PAOP or PaO2/FIO2. Thus, Lop has a beneficial
      effect in the treatment of patients with low cardiac output immediately after
      cardiac surgery.

PMID- 9283161
TI  - [Intrathecal midazolam attenuates renal sympathetic nerve activity in rabbits].
AB  - We hypothetized that intrathecal (IT) midazolam (M) affects renal sympathetic
      nerve activity (RSNA) via benzodiazepine receptors (BZR) at the spinal cord.
      Under alpha-chloralose anesthesia, 26 rabbits underwent surgical procedures for
      the cannulation to femoral artery and vein for measuring blood pressure and
      infusing lactated Ringer solution, respectively. Intrathecal cannulation was
      performed at the 7th thoracic vertebral level. RSNA was recorded from the nerve
      raw between the renal artery and vein using a left flank incision. In the
      neuraxis-intact rabbits, IT administration of low dose M (0.50%) did not affect
      heart rate (HR), mean arterial pressure (MAP), and integrated RSNA (IRSNA). High
      concentration of M (0.5%) increased HR, decreased MAP and attenuated IRSNA
      significantly. In the sino-aortic denervated rabbits, IT administration of 0.5% M
      decreased MAP and IRSNA, but intravenous 0.2 flumazenil rapidly and significantly
      increased MAP and IRSNA. This finding suggests that the decrease in IRSNA
      followed by IT M derives from BZR. In conclusion, IT high concentration of M
      attenuated RSNA through BZR.

PMID- 9283163
TI  - [The effect of preoperative epidural morphine on postoperative pain].
AB  - Postoperative analgesia was assessed by examining nurses' records of 421
      gynecological operative cases between January, 1989 and November, 1990. The
      criterion used in the analysis was the need for analgesics for pain within 24
      hours postoperatively. After receiving morphine (2 mg, 4 mg, 5 mg, 6 mg) with
      local anesthetics or physiological saline solution into the epidural space (lower
      thoracic, lower lumbar, or both regions), the patient was intubated with
      thiopental, diazepam, and a muscle relaxant (vecuronium or pancuronium).
      Anesthesia was maintained with N2O, O2 and vecuronium or a pancuronium
      supplemented with a low concentration of enflurane or without enflurane. In the
      control group, anesthesia was maintained with an epidural block with local
      anesthetics and N2O, O2 supplemented with enflurane or without enflurane. In the
      groups receiving 2 mg or 4 mg of morphine, the percentage of patients with pain
      was 69.4+ (34 out of 49 cases) and 54.5% (30 out of 55 cases), respectively.
      Also, in the groups receiving 5 mg or 6 mg of morphine, the percentage of
      patients with pain was 39.5% (15 out of 38 cases) and 22.4% (51 out of 224
      cases), respectively. In the control group, (with no epidural morphine) 89.1% (49
      out of 55 cases) required analgesics. The percentage of patients without pain was
      significantly larger in the group receiving 6 mg of morphine even in comparison
      with the groups receiving lesser doses. No serious complications occurred
      postoperatively in any group. In conclusion, preoperative morphine administered
      into the epidural space is effective for postoperative analgesia in gynecological
      operation, especially when morphine 6 mg was administered in the lower epidural
      (4 mg) and lower lumbar epidural (2 mg) space.

PMID- 9283162
TI  - [Adrenergic receptor and alpha 2 agonist--4: Applied and clinical pharmacology of
      alpha 2 agonist].
AB  - Alpha 2 adrenergic agonists currently are used in the anesthetic management of
      the surgical patient for their sedative/hypnotic, anesthetic-sparing, analgesic,
      and sympatholytic properties. Experimental and clinical studies have progressed
      to the point where anesthesiologists are now focusing on the use of these agents
      for their analgesic and anesthetic effects. This interest has coincided with the
      development and clinical introduction of dexmedetomidine. Clinical studies using
      existing alpha 2 agonists have revealed a tremendous potential for these agents
      that will be fully realized when more selective and specific compounds become
      available.

PMID- 9283164
TI  - [Continuous epidural morphine for postoperative pain relief after spinal surgery-
      use of an epidural catheter placed at the time of surgery].
AB  - Postoperative analgesia by continuous epidural morphine infusion after spinal
      surgery was investigated in a retrospective study. An epidural catheter was
      placed by surgeons at the time of surgery. Postoperative pain was less intense
      and use of analgesics and sedative was less frequent in patients with continuous
      epidural morphine (n = 41) as compared with patients without continuous epidural
      morphine (n = 41). Among the patients with continuous epidural morphine,
      postoperative pain in patients (n = 16) with the dura opened or dural rent during
      surgery was less intense and the uses of analgesics and sedative was less
      frequent as compared with patients (n = 25) without the dural rent. There were no
      severe complications except for respiratory depression in a patient with chronic
      obstructive pulmonary disease. Our study demonstrated the ease of insertion of an
      epidural catheter at the time of surgery and the good quality of epidural
      analgesia after spinal surgery.

PMID- 9283166
TI  - [Anesthesia for a patient with laryngotracheoesophageal cleft].
AB  - We report anesthetic management of a patient with laryngotracheoesophageal cleft
      which lacks partition between the esophagus and upper airway, a rare congenital
      anomaly with a high mortality. A male baby weighting 2.96 kg was born at 39-week
      gestation. He had respiratory distress, hoarse cry and cyanosis on feeding.
      Gastric cardioplasty was scheduled at the age of 10 days, under the presumptive
      diagnosis of gastroesophageal regurgitation. Endotracheal intubation was
      performed and anesthesia with 1-3% sevoflurane and 100% oxygen was started.
      However, SpO2 dropped suddenly and transiently. Endoscopic examination performed
      transnasally and through the endotracheal tube demonstrated that the septum
      between the trachea and esophagus was absent from the larynx through the entire
      length of the trachea. On the basis of these finding, this case was diagnosed as
      laryngotracheoesophageal cleft (type 3). Esophageal division and gastrostomy were
      performed to prevent regurgitation and aspiration of gastric content.

PMID- 9283165
TI  - [Anesthesia for a patient with heparin-induced thrombocytopenia: a case report].
AB  - A 68 year-old man underwent a femoral-popliteal bypass surgery. He was diagnosed
      as heparin-induced thrombocytopenia (HIT) by platelet aggregation test when he
      underwent CABG 4 years ago. For the present surgery we administered nafamostat
      mesilate and urokinase for anticoagulation during surgery instead of heparin.
      After the operation, laboratory studies showed no thrombocytopenia.

PMID- 9283167
TI  - [General anesthesia for an infant with Rubinstein-Taybi syndrome].
AB  - A 5-year-old girl with Rubinstein-Taybi syndrome (RTS) was scheduled for
      ophthalmic surgery under general anesthesia. RTS is a well-defined syndrome with
      facial abnormalities including a high palate and micrognathia, broad thumbs and
      big toes, and mental retardation as main clinical features, which may be
      complicated with repeated respiratory infections, cardiac anomalies, and so on.
      Anesthesia was uneventfully induced and maintained with the inhalation of oxygen,
      nitrous oxide and sevoflurane. Special attention was paid to the possibilities of
      the difficult airway, aspiration pneumonia and cardiovascular dysfunction during
      anesthesia. No complications were observed throughout the perioperative
      procedures.

PMID- 9283168
TI  - [Heart rate changes in propofol anesthesia--relation with excitatory movements].
AB  - Acceleration of heart rate simultaneously with excitatory movements was observed
      during anesthesia with propofol in four patients. Anesthesia was induced with
      propofol 2.5 mg.kg-1 i.v. and maintained with propofol 10 mg.kg-1.hr-1 i.v. About
      ten minutes after the induction, the patients showed jerking movements such as
      pronation or flexion of their arms, and/or plantar flexion. These movements
      lasted one or two seconds and appeared two or three times a minute. Three
      patients received vecuronium 0.1 mg.kg-1 and even after muscular relaxation
      acceleration of heart rate persisted. In one of two patients who had received
      midazolam 0.8 mg.kg-1, heart rate acceleration ceased. In one patient
      acceleration of heart rate and excitatory movements stopped after reducing the
      infusion rate of propofol from 10 mg.kg-1.hr-1 to 3 mg.kg-1.hr-1. Another patient
      with no involuntary movements showed no heart rate changes. These results suggest
      that heart rate acceleration in four patients was closely related to excitatory
      movements caused by propofol. As it was not influenced by muscular relaxation,
      heart rate monitoring would be useful to detect latent excitatory movements under
      muscular relaxation.

PMID- 9283169
TI  - [Anesthetic and perioperative management of a neonatal vein of Galen malformation
      with multiple organ failure].
AB  - We treated a neonate in intractable cardiac failure due to a vein of Galen
      malformation. She manifested severe multiple organ failure. Perioperative
      problems are cardiac failure, respiratory failure, renal as well as hepatic
      dysfunction, and coagulopathy. Direct clipping of the feeding arteries improved
      her symptoms. Anesthetic problems encountered in this patient are massive
      bleeding and drastic circulatory changes while clipping the feeding arteries,
      increased intracranial pressure and brain ischemia, and other underlying
      complications; hepatic and renal dysfunction, respiratory failure and
      coagulopathy.

PMID- 9283170
TI  - [Anesthetic management of parturients with intracranial arteriovenous
      malformation].
AB  - We have retrospectively analyzed twelve pregnancies in nine patients with
      intracranial arteriovenous malformation (AVM) managed at our hospital from 1984
      to 1995. Following radical excision of AVM before or during pregnancy in 6 cases,
      transvaginal deliveries were performed without untoward sequelae. In three of
      five patients who received non-curative treatments, labor analgesia was provided
      using epidural local anesthetics. One patient who presented with ruptured AVM
      followed by medical therapy, elective cesarean section was performed under spinal
      anesthesia with a favorable outcome. Anesthesia courses in two patients for the
      resection of ruptured AVM during pregnancy were uneventful under enflurane and
      nitrous oxide anesthesia, or balanced anesthesia using fentanyl and nitrous oxide
      in oxygen. Simultaneous cesarean section craniotomy was not performed at our
      hospital.

PMID- 9283171
TI  - [Airway difficulty associated with multiple teratisms of the oral cavity in a
      newborn infant].
AB  - A 13-day-old infant with multiple teratisms of the oral cavity was scheduled for
      resection of the epignathus. Her oral cavity was occupied by large epignathus,
      submandibular tumor, congenital bifid tongue and cleft palate, but she had no
      other congenital abnormalities. We anticipated that an endotracheal intubation
      would be difficult because of the large size of the tumor in relation to the oral
      cavity. Initially, awake intubation using a standard laryngoscope was attempted.
      Although a large elastic epignathus did not interrupt the insertion of the curved
      laryngoscope blade, the hard submandibular tumors protruded from the submaxillary
      ramport interfered with mid-line management of the laryngoscope. After several
      attempts of intubation, a better exposure was obtained and she was successfully
      intubated using a stylet under deep sedation. We recognized that a careful
      observation of anatomical abnormalities in the oral cavity is important to keep
      airway in an infant with multiple abnormalities of the oral cavity.

PMID- 9283172
TI  - [Two cases of anaphylactic shock induced by chlorhexidine].
AB  - We reported two patients who developed skin eruptions and severe hypotension
      immediately after scrubbing their wound in the leg using 4% chlorhexidine
      solution. Both patients were successfully treated by epinephrine administration.
      Patient-1 (a 42-year-old man) had his wound scrubbed using this antiseptic
      several times before the operation. He showed a positive skin scratch test for
      chlorhexidine. Patient-2 (a 74-year-old man) had no prior treatment with
      chlorhexidine. Positive lymphocyte transformation test was not demonstrated in
      these patients. It has been reported that more than 10% of patients with
      anaphylactic shock induced by chlorhexidine use had previous exposure to it and
      80% of them had it used for mucosa or wound washing. From these results, we
      should keep it in mind that chlorhexidine is not likely to be a safe antiseptic
      and can possibly induce anaphylactic shock.

PMID- 9283173
TI  - [A case of transient cortical blindness due to reversible ischemic neurological
      deficit (RIND) after caesarean section under lumbar anesthesia].
AB  - We report a case of 31-year-old woman with pregnant toxicosis, who developed
      transient blindness after caesarean section under lumbar anesthesia. The patient
      was hypoxic due to atelectasis when she developed blindness, but she had no
      ophthalmologic abnormalities. MRI depicted abnormal high intensity areas (HIA)
      with T 2-weighted images (T 2 WI) in the occipital lobes and the basal ganglia.
      CT could not detect any of these MRI findings. The patient regained her vision
      four days after the onset. The HIA disappeared in a follow up MRI (T 2 WI) two
      weeks after the onset. The patient was diagnosed as cortical blindness due to
      RIND. Although most of the transient cortical blindness are accompanied with
      pregnant toxicosis with hypertension, there are some cases without pregnant
      toxicosis. We stress the importance of maintaining the blood pressure within the
      normal range in patients with hypertension who undergo surgery under spinal
      anesthesia.

PMID- 9283174
TI  - [Propofol anesthesia for a schizophrenic patient].
AB  - A 41-year-old man weighing 68 kg was scheduled for bilateral tonsillectomy
      because of palmoplantar pustulosis. The patient had been diagnosed as
      schizophrenic 10 years earlier. Psychotropic agents, mosapramine (75 mg.day-1),
      bromperidol (6 mg.day-1), cloxazolam (3 mg.day-1), biperiden (1 mg.day-1) and
      nitrazepam (5 mg as needed), were administered until the day before surgery. On
      the day of surgery, atropine (0.g mg) and midazolam (4 mg) were administered
      intramuscularly as premedication. Anesthesia was induced by intravenous propofol
      (120 mg) and fentanyl (100 microgram) followed by nasotracheal intubation using
      vecuronium (7 mg). Anesthesia was maintained with inhalation of oxygen and
      nitrous oxide (2 l.min-1 each) and the intravenous infusion of propofol (5-10
      mg.kg-1 x h-1) supplemented by fentanyl (100 microgram). The patient recovered
      from anesthesia uneventfully. Immediately after surgery, intravenous haloperidol
      (5 mg) and intramuscular biperiden (1 mg) were given. The daily oral
      administration of psychotropics was resumed on the first postoperative day. There
      were no complications such as hypotension, arrhythmia, or worsening of the mental
      condition, throughout the course.

PMID- 9283175
TI  - [Automated anesthesia record keeping system in in the United States].
AB  - We have implemented an automated anesthesia record keeping system (AARK) since
      1992. The system stands in need of re-designing to function as a perioperative
      patient's information system. We discussed the issues with anesthesiologists
      who's institutes are implemented with AARK in the United States. We visited the
      following three institutes: St. Luke's Hospital (Kansas City, MO), University of
      Florida (Gainesville, FL), and Burbank Hospital (Fitchburg, MA). All of them are
      implemented with ARKIVE system. Dr. Edsall in Burbank Hospital stressed quality
      assurance (QA), and using ARKIVE's database for QA. University of Florida has a
      big anesthesia and engineering team to develop a new ergonomically sound AARK.
      Some of the members regarded ARKIVE as an "out of date" system. Dr. Tuohy in St.
      Luke's Hospital stressed cost/benefit of AARK. Taking their experience into
      account, we are designing a new perioperative patient's information system
      including AARK.

PMID- 9283176
TI  - Medicine behind bars and other lessons from the AIDS epidemic.

PMID- 9283177
TI  - Mad dogs and Englishmen.

PMID- 9283178
TI  - The Brown University School of Medicine, Class of 1997.

PMID- 9283180
TI  - Where are they now?

PMID- 9283179
TI  - Out of the ivory tower; medical education returns to the community.

PMID- 9283182
TI  - The longest night.

PMID- 9283181
TI  - Physicians newly licensed in Rhode Island during 1996.

PMID- 9283183
TI  - Hospital discharges with asthma, 1991-1995.

PMID- 9283184
TI  - Physicians dumping iron.

PMID- 9283185
TI  - How much does a MCO enrollee need to know about provider financial incentives?

PMID- 9283186
TI  - Monoconjugated bilirubin as a possible factor in cholesterol gallstone
      pathogenesis.
AB  - HPLC determination of bilirubin conjugates in bile demonstrated a subgroup of
      patients with cholesterol gallstones who have more monoconjugated than
      diconjugated bilirubin in their gallbladder bile. None of the patients had
      abnormal liver function tests nor hemolysis. It was shown that this is not due to
      differences in liver secretion of the conjugates. In these patients, the more
      insoluble monoconjugated bilirubin might have provided the nucleus for the
      subsequent crystallization of cholesterol leading to the formation of cholesterol
      gallstones.

PMID- 9283187
TI  - Intracranial epidermoid and dermoid cysts. Results of microneurosurgery.
AB  - The authors present their series of intracranial epidermoid and dermoid cysts.
      Clinical, radiological and anatomopathological features of these tumors are
      analyzed. Appropriate surgical treatment and results are discussed in light of
      the pertinent literature.

PMID- 9283188
TI  - [Recovery of the "instrument-hand" and the "communication-hand" in the
      hemiparetic child].
AB  - BACKGROUND: Rehabilitation techniques have always attached great importance to
      the recovery of hand functions in the different forms of child cerebral palsy.
      The human hand has complex structure and functions, and it can be defined as
      "instrument-hand", "expression-hand", "relation-hand" and "constant challenge to
      rehabilitation programmes. Among the most common techniques used today,
      neuromuscular facilitation allows the recovery only of the instrumental function,
      and cortical facilitation allows only the awareness of the motor learning. The
      psychomotor approach is aimed at a global recovery of the gesture, i.e. at the
      restoration of the movement neurophysiologic, relational and interactive aspects.
      Aim of this paper is to evaluate the possibility of restoring the hand
      communicative function in children with paresis. METHODS: Ten patients (6 males
      and 4 females; age range 20 months-8 years) with hemiparesis not associated with
      other disorders undergoing psychomotor therapy were compared with 10 controls (5
      males and 5 females) undergoing traditional therapy (generally following Bobath).
      RESULTS: The communicative function of the hemiparetic hand was restored in 8
      patients compared to 2 patients in the control group. CONCLUSIONS: Even though
      our series includes few cases and it is not possible to draw any definitive
      conclusion, it is reasonable to hypothesize that the psychomotor approach is a
      therapeutic model able to restore the hand complex functions.

PMID- 9283189
TI  - Mandatory treatment from the family's perspective.
AB  - Families' difficulties in getting treatment for highly disruptive, assaultive, or
      suicidal family members are compounded by patients' resistance, their resentment
      if relative seek forced interventions, and systemic and legal barriers to timely
      care. Consumer services and outreach may be a route to voluntary treatment.

PMID- 9283190
TI  - The mental health service consumer's perspective on mandatory treatment.
AB  - The nature of serious mental illness is such that patients are not always willing
      to accept the treatments providers deem appropriate for them. At times such
      treatment is mandated against the expressed wishes of the client. This chapter
      provides an overview of consumer perspectives on this process.

PMID- 9283191
TI  - Mandatory treatment: an examination of therapeutic jurisprudence.
AB  - Mandatory treatment may have both positive and negative effects on patient
      outcomes. This chapter discusses empirical research and psychological theory
      bearing on the effects of coercion and choice and suggest ways that clinicians
      can apply the law more effectively in mandatory treatment contexts.

PMID- 9283192
TI  - Involuntary treatment of substance abuse disorders.
AB  - The authors argue for the extension of mandatory treatment to persons gravely
      disabled by substance abuse. The problem is examined from ideological, clinical,
      legal, economic, and ethical perspectives.

PMID- 9283194
TI  - Conditional release: court-ordered outpatient treatment for insanity acquittees.
AB  - Experience with involuntary outpatient treatment of individuals conditionally
      released to the community after a finding of nt guilty by reason of insanity
      provides insight into the involuntary treatment of all mental health clients,
      particularly those considered to be high risk.

PMID- 9283193
TI  - What happens when effective outpatient civil commitment is terminated?
AB  - Outpatient civil commitment can be effective in slowing the revolving door for
      selected patients, but it may not be the best mechanism for ensuring treatment
      over time.

PMID- 9283195
TI  - Court-authorized medication for incompetent hospitalized patients.
AB  - The authors provide an overview of recent developments affecting court-authorized
      treatment of incompetent patients, focusing on a state psychiatric system that
      has historically been in the vanguard in this arena in the United States.

PMID- 9283196
TI  - A competency-based approach to court-ordered outpatient treatment.
AB  - A quasi-experimental study of involuntary outpatient treatment in Massachusetts
      is described and analyzed. Results indicate decreased hospital use by the
      involuntarily treated outpatients, which may or may not be due to the involuntary
      intervention itself.

PMID- 9283197
TI  - [Ethics for the welfare of animals on animal experimentation].

PMID- 9283198
TI  - Bupivacaine combined with isoflurane synergistically depressed myocardial
      contractility in rat working heart preparation.
AB  - It is well known that both local and volatile anesthetics depress myocardial
      functions. This study was performed to evaluate the combined effects of commonly
      utilized local anesthetics (bupivacaine, mepivacaine, and lidocaine) and a
      volatile anesthetic (isoflurane) on heart rate and myocardial contractility in an
      isolated rat working heart preparation using each local anesthetic at 0 to 3 x
      10(-4) (mol/L) with or without 1 MAC (minimum alveolar concentration) of
      isoflurane. The three local anesthetics depressed the heart rate and myocardial
      contractility dose-dependent. Bupivacaine depressed the heart rate more than the
      other two local anesthetics. One MAC isoflurane showed significant negative
      inotropic effects, and accelerated the effects of the local anesthetics. By using
      isobolographic analysis, we concluded that the combined effect of isoflurane and
      bupivacaine on myocardial negative inotropism was synergistic, while the effects
      of isoflurane and mepivacaine or lidocaine were additive.

PMID- 9283199
TI  - [Anterior cruciate ligament reconstruction with the patellar tendon augmented by
      absorbable artificial materials. A histological and molecular biological study in
      rabbits].
AB  - An experimental study was performed to investigate the histological and molecular
      biological properties of reconstructed anterior cruciate ligaments (ACL) using
      the patellar tendon augmented by absorbable artificial material in rabbits.
      Thirty rabbits underwent ACL reconstruction with the patellar tendon (non
      augmented group), and 30 with the patellar tendon augmented by a polyglactin 910
      mesh (augmented group). They were respectively sacrificed at at 1, 2, 3, 4, 6, 8
      and 12 weeks after surgery for histological and molecular biological examination.
      Histologically, the fibrocytes were disappeared in deep portion of transplanted
      graft at 2 weeks after surgery in both groups. The graft was replaced with
      granulated tissues at 6 weeks in the augmented group, but it took 8 weeks in the
      non-augmented group. At 12 weeks, the graft showed hypocellularity with regularly
      oriented fibers in the augmented group, while it still showed hypercellularity
      with disoriented fibers in the non-augmented group. Molecular biologically, after
      the reconstruction at one week, the relative radioactivity in the graft was 1.05
      in the non-augmented group, and 2.10 in the augmented group. Additionally the
      level of the alpha 2 (I) collagen mRNA was also significantly higher in the
      augmented group than that in the non-augmented group. These results suggested
      that a polyglactin 910 mesh had an effect on the process of reorganization and
      remodeling in the transplanted patellar tendon during the post-operative period
      in rabbit.

PMID- 9283201
TI  - Threshold of ventral root stimulation to produce the IS-spike without the M-spike
      in the same cat motoneuron.
AB  - In cats, anesthetized with pentobarbital sodium and immobilized with d
      tubocurarine, it was discovered by changing the strength of L 7 or S 1 ventral
      root (VR) stimulation that the stimulation could produce in the same motoneuron
      the IS-spike, i.e., the spike of the initial segment, either via the M-spike or
      without the M-spike, which is believed to be the spike of the node of Ranvier as
      recorded in the soma. It was shown by simultaneously recording the compound
      action potential of the L7 or S 1 ventral root that the threshold of VR
      stimulation to produce the IS-spike via the M-spike was higher than that to
      produce it without the M-spike in all 18 motoneurons in which the threshold was
      studied. With weaker stimulation the M-spike was not produced and the IS-spike
      arose from a potential smaller than the M-spike (the M-potential) or directly
      from the baseline. The M-potential could also trigger the M-spike. These results
      disclose the possibility that the M-spike originates not in the axon, but
      somewhere else such as the dendrite.

PMID- 9283200
TI  - A comparative analysis of the transplant potential of umbilical cord blood versus
      mobilized peripheral blood stem cells.
AB  - Human umbilical cord blood (UCB) is currently considered as a third source of
      hematopoietic stem cells for transplantation, following the bone marrow and
      growth-factor-mobilized peripheral blood (MPB). To evaluate the potential
      benefits of UCB, we performed a comparative study of the properties of the stem
      cells in UCB and MPB samples. CD 34+ cell determination and CFU-GM colony assay
      showed a lower frequency of committed progenitors in UCB than in MPB. In
      contrast, a higher of the CD 34+ CD 38- subset in UCB suggested that more
      primitive, multipotent progenitors are enriched in UCB than in MPB. Phenotypic
      analysis of UCB lymphocytes revealed a reduced level of T cell subsets,
      especially cytotoxic CD 8+ lymphocytes, which might minimize graft versus host
      disease in clinical practice. In conclusion, UCB is an attractive alternative
      source for stem cell transplantation, but ex vivo expansion of stem/progenitor
      cells could be effective for attaining rapid and safer hemopoietic
      reconstruction.

PMID- 9283203
TI  - Evaluation of coronary collateral circulation in early ischemia in rat hearts. A
      morphological study.
AB  - Histological changes were examined in the left ventricular free wall of the heart
      in 40 rats after ligation of the distal anterior descending coronary artery for
      15, 30 minutes and 1, 2, 3, 4, 5, 6 hours. Auto-injection of tracers for light
      microscopy was used to examine the development of collateral circulation.
      Morphological changes of the ischemic myocardium were observed by PAS staining
      and transmission electron microscopy. Fifteen minutes after coronary occlusion,
      the dye was observed in the vein of the ischemic zone; however, 30 minutes after
      coronary occlusion, the dye appeared in the capillaries of the outer-third layer.
      These findings suggested that the collateral circulation becomes functional
      between 15 and 30 minutes after coronary occlusion. Collateral circulation
      increased gradually in the capillaries of the ischemic zone. Thirty minutes after
      coronary occlusion the dye was seen only in the outer-third layer of the
      ventricular ischemic zone. One hour after occlusion, the dye appeared in the
      superficial space and the middle-third layer. Three hours after occlusion, the
      dye was seen in all layers of the ischemic zone. The dye appeared in the ischemic
      zone, where myocardium damage was not homogeneous. The positive reaction obtained
      by PAS staining corresponded with the capillaries, veins and superficial spaces
      in which the dye was evident. These results suggest that collateral circulation,
      verural back flow and superficial space flow are able to prevent myocardial
      infarction in early ischemia.

PMID- 9283202
TI  - Extrasomatic spikes recorded from cat motoneurons. Possible dendritic spikes.
AB  - Extrasomatic (ES-) spikes were recorded in motoneurons in cats anesthetized with
      pentobarbital sodium and immobilized with d-tubocurarine. ES-spikes, 40-79 mV in
      amplitude, were distinguished from intrasomatic spikes by their differences in
      responses to a train of 8 pulses at 500 Hz given to the L 7 or S 1 ventral root.
      In 23 motoneurons 3-6 different spikes could be recorded from the same site in
      the same cell in response to the ventral root stimulation. It was not possible to
      explain these multiple spikes as axon spikes or IS-(initial segment) spikes
      because too many spikes were observed at the same site. Accordingly, it was
      suggested that they were dendritic in origin.

PMID- 9283204
TI  - Reduction in amplitude of the ventral root elicited small spike by dorsal root
      stimulation in cat motoneurons.
AB  - Ventral root stimulation is known to produce two spikes, large and small, in the
      alpha-motoneuron. Since it is the small spike that triggers the outgoing impulse
      from the cell it is regarded as the key potential in information processing of
      the cell and referred to either as the IS-spike or as the A-spike depending upon
      whether one considers it as a purely single spike or as a composite spike. The
      small spike was elicited by stimulating the L 7 or S 1 ventral root in cats
      anesthetized with pentobarbital sodium and immobilized with d-tubocurarine.
      During the later phase of the excitatory prostsynaptic potential and thereto
      following inhibitory postsynaptic potential (IPSP) produced by stimulating the
      corresponding dorsal root the amplitude of the small spike was reduced by about
      20%. This could be either explained as due to reduction in impedance of the
      membrane generating the small spike or interpreted as suggesting that the small
      spike is a composite spike and some of its components were inhibited by the IPSP.
      This interpretation was favored because the reduction occurred not when the
      safety factor for antidromic impulse transmission was high, but when it was low.

PMID- 9283205
TI  - [An investigation of drug abuse and the utility of toxicology screening for use
      in emergency centers].
AB  - The results of toxicology screening of samples from 725 patients admitted to the
      Critical Care Medical Center (CCMC) of Nippon Medical School during a 10-month
      period from 1992-1993 (Group A) and a 4-month period from 1995-1996 (Group B)
      were discussed. We investigated the drug use of emergency patients using
      immunoassay. EMIT and Triage. The results were confirmed by Gas
      Chromatography/Mass Spectrometry (GC/MS). Blood samples were analyzed for ethanol
      (EtOH) by head space gas chromatography. Overall, 18% of the 725 cases tested
      positive for drugs, 13% for EtOH. Recently the positive rates of drugs and EtOH
      have been increasing. The positive rates for drugs in Group A and Group B were
      15% and 23%, and EtOH were 11% and 17%, respectively. False positive cases caused
      by the cross-reactivity to analog were found in both EMIT and Triage. But the
      reliability of both methods was sufficient for clinical use. Rapid in easy
      toxicology screening can provide useful clinical information for patients
      admitted to a CCMC, especially for patients who have been injured, have sustained
      unknown-etiology consciousness disturbances, have CPAOA (Cardio Pulmonary Arrest
      on Arrival) or have committed drug abuse. We conclude that toxicology screening
      using immunoassay methods is suitable for use in an emergency center.

PMID- 9283206
TI  - [Diagnosis and treatment of Helicobacter pylori].

PMID- 9283207
TI  - [Pulmonary hemosiderosis].

PMID- 9283209
TI  - [The role of nitric oxide in mercury chloride-induced vasculitis in the brown
      Norway rat].
AB  - Nitric oxide (NO) is an important factor in tissue trauma, but its detailed role
      in the pathogenesis remains unknown. In autoimmune vasculitis, it is possible
      that NO in one of the factors underlying tissue trauma and induction of
      autoimmune antibodies. To study its role on an animal model using mercury
      chloride (HgCl2), Brown Norway rats (BN rats) were given five injections of]
      HgCl2, each 1 mg/kg, over 10 days. Vasculitis and production of some autoimmune
      antibodies developed after HgCl2 injections. Urine nitrate/nitrite, metabolic
      production of NO, was produced in advance of the production of other autoimmune
      antibodies. To elucidate the role of NO, NG-nitro-L-arginine methyl ester (L
      NAME), which is a nitric oxide synthase (NOS) inhibitor, was given in addition to
      HgCl2, at the daily dose of 30 mg/kg. There was no difference in production of
      autoimmune antibodies between this group and the control group, but urine protein
      excretion was suppressed in the HgCl2 + L-NAME group (p < 0.001). By
      immunohistochemical study, inducible NOS was positive in small vessels and
      mesangial cells in rat kidney. We conclude that in this animal model, over
      production of NO leads to the production of autoimmune antibodies and inhibition
      of NOS production ameliorates proteinuria. These results suggest that NO plays an
      important role in the induction of renal injury in the rat model of autoimmune
      vasculitis.

PMID- 9283208
TI  - Comparison of pre-operative psychological evaluations and clinical results in
      patients with spinal disorders.

PMID- 9283210
TI  - [Effects of high fat diet and a novel antioxidant (BO653) on ischemia reperfusion
      injury of rat kidney].
AB  - The effect of a high fat diet (HFD) on renal function, renal mitochondrial
      function and intrarenal oxygen-free radial scavenging activity were examined in
      the ischemia-reperfusion model of the rat kidney. Whether of not a novel
      lipophilic antioxidant (BO653) could minimize this effect in vivo was also
      investigated. Thirty minutes renal ischemia was introduced by vascular clamp in
      rats with or without HFD (cholesterol 1.25%). Some of the HFD rats received BO653
      by gastric gavage. Creatinine clearance (Ccr) was measured 24 hours following the
      injury. Mitochondrial oxygen consumption and thiobarbituric acid reactive
      substance (TBARS), superoxide dismutase (SOD), glutathione peroxidase (GPX) and
      alpha-tocopherol were measured in the kidney before, 30 min ischemia and 30 min
      after reperfusion. HFD significantly reduced Ccr after ischemia-reperfusion (45%
      decreased compared to normal diet), which was ameliorated by BO653. Thirty-minute
      ischemia deteriorated the mitochondrial function in the normal diet (ND) group,
      high fat diet (HFD) group and high fat diet + BO653 (HFD + BO) group. Thirty
      minute reperfusion ameliorated the mitochondrial function in all those groups.
      The kidney content of TBARS was not increased after the ischemia-reperfusion in
      all these groups. In the HFD group, the kidney content of GPX was higher than in
      the ND group during ischemia-reperfusion, but in the HFD group, the kidney
      content of SOD was significantly decreased after the thirty-minute ischemia.
      Thirty-minute ischemia decreased the kidney content of alpha-tocopherol in the
      HFD group, which was recovered by the thirty-minute reperfusion. In conclusion, a
      high fat diet deteriorates ischemia-reperfusion injury of the rat kidney and
      BO653 ameliorated this effect judged by creatinine clearance and renal
      mitochondrial function. Reperfusion injury could not be confirmed in the present
      model based on the results of lipid peroxidation and oxygen-free radical
      scavenging enzyme activity.

PMID- 9283211
TI  - [Protection afforded by a novel K channel opener (Y-26763), against glycerol
      induced acute renal failure (ARF) in rats].
AB  - Y-26763, a benzopyran derivative, is a newly developed ATp-sensitive K channel
      opener and has been reported to protect against ischemic acute renal failure
      (ARF). We examined the effects of Y-26763 on glycerol-induced myoglobinuric ARF
      in the rats. ARf was induced in 28 adult male Sprague-Dawley rats by hind-limb
      intramuscular injection of 50% glycerol (5 ml/kg) after 18 hrs of water
      deprivation. Y-26763, 7 micrograms/kg (GY group, n = 10) of vehicle (G group, n =
      12) was given intravenously 15 min before glycerol injection. Glibenclamide (20
      mg/kg), a K channel blocker was given prior to Y-26763 injection to see of the
      effects was due to the K-channel opener (GYG group, n = 6). Animals were
      sacrificed 24 or 96 hrs after glycerol injection. Y-26763 partially, but
      significantly, restored renal dysfunction 24 hrs after ARF. Pcr (mg/dl) and Ccr
      (ml/min), respectively were as follows: G group, 5.7 +/- 0.4, 0.015 +/- 0.006; GY
      group, 4.1 +/- 0.4, 0.061 +/- 0.027 (p < 0.05). These favorable effects were
      antagonized by glibenclamide (Pcr in GYG group, 5.4 +/- 0.3 mg/dl, p < 0.05).
      Renal calcium content was not statistically significant (3.5 +/- 1.2 vs. 3.4 +/-
      1.2 micrograms/mg dry weight). Histological examinations revealed that extensive
      tubular necrosis and cast formation seen in the G group were reduced in the GY
      group. At the recovery phase, 96 hrs after glycerol injection, Y-26763
      accelerated the recovery from ARF as shown in Pcr (mg/dl) and Ccr (ml/min): 4.3
      +/- 0.2, 0.05 +/- 0.01 in the G group, 2.8 +/- 0.2, 0.13 +/- 0.02) in the GY
      group (p < 0.01). In conclusion, Y-26763 partially protected against glycerol
      induced ARF.

PMID- 9283212
TI  - [Serum levels of amino acid in patients with purple urine bag syndrome].
AB  - The plastic of urinary catheter drainage bags occasionally turns purple hours or
      days after catheterization and the color becomes increasingly intense the longer
      the same drainage system is left in place. This phenomenon was first reported in
      1978 as "purple urine bag syndrome", and had been known to occur with bacterial
      infection of the urinary tract with chronic constipation. Chronic constipation is
      commonly associated with bacterial overgrowth in the bowel in which tryptophan
      has been converted to indol and yields the high levels of indigo (blue) and
      indirubin (red) in urinary bags of patients with bacterial infection of the
      urine, because indigo-producing bacteria have indoxyl phosphatase or sulfatase
      that can produce indigo and indirubin. We determined the serum levels of amino
      acids in patients with purple urine bag syndrome. The serum level of tryptophan
      and valine were significantly reduced in patients with purple urine bag syndrome.
      This result suggests that absorption of amino acids was affected by disturbances
      of colonic motility and intestinal bacterial overgrowth.

PMID- 9283214
TI  - [A clinicopathological study of 90 children with acute renal failure].
AB  - Clinical presentation, laboratory findings, renal biopsy findings and subsequent
      clinical course were studied retrospectively in 90 children with acute renal
      failure to intrinsic renal damage. The mean age at presentation was 8.1 years.
      Diagnosis and number of patients were as follows: Hemolytic uremic syndrome (HUS)
      in 32 patients, tubulo-interstitial nephritis in 19, idiopathic nephrotic
      syndrome in 10, IgA nephropathy on 9, membranoproliferative glomerulonephritis in
      8, lupus in 5, poststreptococcal glomerulonephritis in 4, cortical necrosis in 1,
      Henoch Schoenlein purpura nephritis in 1 and anti-neutrophil cytoplasmic antibody
      associated glomerulonephritis in 1. Thirty-nine patients needed dialysis, but 36
      of these were able to stop dialysis, 3 patients with HUS without gastrointestinal
      symptoms needed chronic dialysis. The mean follow-up period was 7.3 years from
      onset, and the the latest follow-up 82 patients had normal renal function, 3
      showed chronic renal failure, 2 had regular dialysis, 2 had successful renal
      transplantation, an 1 had died due to heart failure. A poor outcome was
      associated with diffuse crescents and the presence of severe vascular changes.
      The early biopsy findings were very useful for the management of children with
      acute renal failure.

PMID- 9283213
TI  - [Study on coagulation fibrinolytic systems in predialysis patients with chronic
      renal failure--comparison between patients with chronic glomerulonephritis and
      patients with diabetic nephropathy].
AB  - To clarify the abnormalities of coagulation and fibrinolytic systems on
      predialysis patients with chronic renal failure, we measured indices of
      coagulation and fibrinolytic systems in 33 predialysis patients whose creatinine
      (Cr) levels were over 3.0 mg/dl. We termed twenty-four patients with chronic
      glomerulonephritis the "CGN group". We also termed nine patients wit diabetes
      mellitus the "DM group". We measured thrombin.antithrombin III complex (TAT),
      alpha 2-plasmin inhibitor plasmin complex (PIC), D-dimer, protein C, protein S,
      thrombomodulin (TM), vitronectin, tissue plasminogen activator.plasminogen
      activator inhibitor-1 complex (tPAI-C) in theses two groups. Furthermore, we
      measured the same indices after 6 months in the CGN group. As a result, the
      plasma levels of both TAT, PIC, TM/Cr ration in the DM group were significantly
      higher that those in the CGN group, changes in both protein S activities and
      plasma levels of tPAI-C were reduced significantly after 6 months. In conclusion,
      the abnormalities of coagulation and fibrinolytic systems in predialysis diabetic
      patients were stronger than those in predialysis patients with CGN. Furthermore,
      these abnormalities were worsened after 6 months in predialysis patients with
      chronic renal failure.

PMID- 9283215
TI  - [Serum transferrin receptor level as an index of the response to erythropoietin
      therapy for anemia in pre-dialysis patients with chronic renal failure].
AB  - In order to reveal whether serum transferrin receptor (sTfR) can serve as an
      index in erythropoiesis during recombinant human erythropoietin (rHuEpo) therapy
      for anemia in pre-dialysis patients with chronic renal failure, we analyzed
      hematopoietic parameters and sTfR levels in 26 patients who were newly
      administered rHuEpo. sTfR was determined as sTfR transferrin complex (TRC) using
      the enzyme linked immunosolvent assay (ELISA) and the latex agglutination
      nephelometric immunoassay (LA). The therapeutic effect of rHuEpo was expressed as
      the change in the Ht from the start of treatment to 8 weeks later. (delta Ht).
      Ht, RBC and Hb levels were significantly increased at 4 and 8 weeks after
      initiating rHuEpo treatment. Furthermore, sTfR levels were significantly
      increased at 2 and 4 weeks after the start of rHuEpo treatment. Absolute changes
      in the sTfR level (sTfR before - sTfR after) and rates of change (absolute
      change/sTfR before x 100) at, 2, 4 weeks after the start of rHuEpo treatment
      showed a significant positive correlation with delta Ht. These results indicate
      that sTfR is a useful marker as an index of therapeutic effect of rHuEpo for
      anemia in pre-dialysis patients with chronic renal failure.

PMID- 9283217
TI  - [A case of nephrotic syndrome associated with minimal renal amyloidosis--a four
      year follow-up].
AB  - A 61-year-old male had nephrotic syndrome in association with minimal renal
      amyloidosis. The amyloid deposits were inconspicuous and had been initially
      overlooked, and the biopsy specimen was thought to show minimal glomerular
      changes. Accordingly he was diagnosed as having minimal change nephrotic syndrome
      (MCNS). Thereafter, administration of 40 mg/day of prednisolone was started. A
      few weeks after treatment, proteinuria decreased, but did not disappear. Four
      years later, he was readmitted for the treatment of the nephrotic syndrome. The
      second biopsy at 65 years of age revealed typical renal amyloidosis by light
      microscopy. Congo red staining and electron microscopy confirmed the presence of
      amyloid deposits. The serum A protein (SAA) level was 328 micrograms/ml.
      Furthermore, the first biopsy specimen revealed minimal renal amyloidosis by
      Congo red staining. At the time, 40 mg/day of prednisolone proved ineffective for
      the proteinuria. However, after methylprednisolone pulse therapy, the proteinuria
      decreased and the nephrotic syndrome improved. After discharge, administration of
      20 mg/day of prednisolone was maintained. One year later, the patient showed no
      evidence of recurrence of the nephrotic syndrome and the SAA level decreased
      (from 328 micrograms/ml to 74.4 micrograms/ml). Prednisolone proved to have a
      beneficial effect on the reduction of proteinuria and SAA levels. We strongly
      recommend careful examination for amyloid deposits in all kidney biopsy specimens
      with the appearance of MCNS on older patients whose proteinuria does not respond
      to the administration of prednisolone.

PMID- 9283216
TI  - [A prospective controlled study of sairei-to in childhood IgA nephropathy with
      focal/minimal mesangial proliferation. Japanese Pediatric IgA Nephropathy
      Treatment Study Group].
AB  - To determine the effect of the Chinese herbal medicine, Sairei-to (TJ-114) in
      children with newly diagnosed IgA nephropathy showing focal/minimal mesangial
      proliferation, we undertook a prospective controlled study. One hundred and one
      patients were randomly assigned to receive Sairei-to for 2 years (group 1) or no
      drug for 2 years (group 2). Forty-six of the 50 patients in group 1 and 48 of the
      51 patients in group 2 completed their trial. At entry, the two groups of
      patients did not differ in the clinical, laboratory and pathologic findings. At
      the end of the trial, urinary protein excretion and hematuria were significantly
      reduced in group 1, but were unchanged in group 2. Twenty-one group 1 patients
      (46%) had normal urine, but only 5 group 2 patients (10%) had normal urine at the
      end of the trial (p < 0.001). Blood pressure and creatinine clearance were normal
      at the end of the trial in all but one group 2 patient, who developed chronic
      renal failure. The present study demonstrates that 2-year Sairei-to treatment
      early in the course of disease is effective in children with IgA nephropathy
      showing focal/minimal mesangial proliferation.

PMID- 9283218
TI  - [A case of anti-basement membrane (BM) mediated disease presenting renal and
      pulmonary symptoms by divergent timing].
AB  - A case of 49-year-old man with anti-GBM antibody and who manifested pulmonary and
      renal symptoms at divergent times. Thirty-six years previously, renal disease
      with unneglectable degree of proteinuria was noticed. One month before admission,
      he was found by chance to have elevated serum creatine (Scr); 3.4 mg/dl. At
      admission, his Scr was 13.7 mg/dl and Hb 12.7 g/dl, TP 5.2 g/dl with 3+
      proteinuria and no glucosuria. He was a heavy smoker and remained so while
      admitted. Renal biopsy presented fibrocellular crescents in 100% of glomeruli
      with striking tubulointerstitial involvement. Immunofluorescence showed linear
      IgG deposition along the glomerular capillary wall. Hemodialysis was instituted,
      and after 13 hospital days, anti-GBM antibody at admission was high at 128 U,
      with negative PANCA. Plasmapheresis was also performed, but on the next day
      pulmonary hemorrhage occurred with a concomitant rise of anti-GBM to 250 U. Thus,
      steroid pulse therapy was conducted in combination with plasmapheresis. Pulmonary
      hemorrhage subsided along with lowering of anti-GBM (48 U), but renal failure
      persisted. The patient died of septicemia. Based on the clinical course of the
      case, the term "anti-BM mediated disease" may more properly delineate the entity
      of the disease rather than the classical eponym "Goodpasture's disease" which
      requires coexistence of pulmo- and renal manifestations for definition.

PMID- 9283219
TI  - [A case of myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA)-positive
      crescentic glomerulonephritis induced by propylthiouracil (PTU)].
AB  - We have experienced a case of myeloperoxidase-antineutrophil cytoplasmic antibody
      (MPO-ANCA)-related glomerulonephritis induced by propylthiouracil (PTU). A 45
      year-old female had been treated with PTU for 4 years after the diagnosis of
      hyperthyroidism. She was referred to out hospital because of abrupt macroscopic
      hematuria and moderate proteinuria after several days of upper respiratory tract
      infection. On admission, her laboratory findings showed deterioration of renal
      function. Renal biopsy revealed crescentic glomerulonephritis without deposition
      of immune complexes. Her serology was found to be MPO-ANCA-positive and
      cytoplasmic-ANCA-negative. Based of these findings, we diagnosed idiopathic
      crescentic glomerulonephritis. Following the initiation of steroid pulse therapy,
      her urinary protein excretion and renal function gradually improved in parallel
      with a decrease in the MPO-ANCA titer. Although steroid therapy effectively
      responded to their renal function without the withdrawal of PTU, it seems that
      PTU may be closely associated with the development of (MPO-ANCA)-related
      glomerulonephritis in this case. Therefore, hyperthyroidism patients treated with
      PTU should be paced under vigilant observation by monitoring their urinalysis and
      serum creatinine level.

PMID- 9283220
TI  - [Establishment of a laboratory information office in response to the expanding
      need for consultation--actual situation of the laboratory information room,
      Clinical Laboratory Department, Kitasato University Hospital].
AB  - Due to the advancement, segmentation and specialization of the medical care,
      laboratory examinations covered by the National Health Insurance (NHI) tariff
      have exceeded several hundred, and it is not possible for medical staff to be
      familiar with all of these and to utilize them appropriately. There is an urgent
      need for laboratory information for physicians, nurses, and other health
      professionals. Accordingly, our Clinical Laboratory Department, Kitasato
      University Hospital, established a "Laboratory Information (Consultation) Office"
      in July 1995 to provide consultations on clinical laboratory tests to those
      engaged in daily clinical practice and in medical research. The office is
      situated on the second floor of the Laboratory Building of the Kitasato
      University Hospital. One laboratory technician and one laboratory physician
      (clinical pathologist) are stationed there. They are available for telephone
      consultations from 9:00 to 17:00 on weekdays, except for holidays, and from 9:00
      to 13:00 on the first, third and fifth Saturdays. In addition, since January
      1997, this office also has been open to members of medical associations in
      various cities in our area. To cope with requests for laboratory information,
      including whether an examination is covered the NHI tariff, selection of
      appropriate screening examinations and availability of new laboratory tests,
      consultations by fax are accepted at any time, even after regular working hours.
      As a post-graduate education program, the clinical laboratory physicians study
      specimen handling analytical methods and interpretation of results. At medical
      staff meeting, personnel from the Laboratory Information Office provide
      clarification on the types of consultations offered, address complex questions
      and find resolutions for rarely encountered and difficult laboratory issues. At
      these meetings, a summary of new laboratory examinations also is presented. This
      system of an information office where full-time laboratory physicians and
      laboratory technicians are stationed is the first such attempt in Japan. It may
      be considered a pilot project to determine if such a system may be applied to
      other laboratory departments in the future.

PMID- 9283221
TI  - [Our experience with a 24-hour on-call program in Nihon University Hospitals].
AB  - We must recognize that undergraduate clinical training is insufficient in Japan
      and that we need to improve the role of the laboratory medicine, especially in
      the area of communication. Therefore, postgraduate training in clinical
      pathology/laboratory medicine should include; 1. Basic clinical skills
      (Communication skills, physical examination and common laboratory procedures such
      as Gram's stain, Wright-Giemsa stain, etc.), 2. Principles, instrumentation and
      techniques of each discipline of this broad scientific field, 3. How laboratory
      information is used in a medical setting, 4. The role of the clinical
      pathologist/laboratory physician in interacting with laboratory staff, physicians
      and patients. There is an increasing gap between the clinic and the laboratory.
      Current needs require us to make a major attempt to bridge this gap. This effort
      will require new and resourceful means of communication and interaction. A 24
      hour on-call program was established to enrich the training of the clinical
      pathology residents in the USA. Each resident in the program is responsible for
      being on call, which entails learning the day-to-day operation of the laboratory
      and being available to interpret laboratory data when the need arises. Residents
      are expected to refer to the appropriate staff member those situations that he or
      she feels unable to handle. A review of all on-call problems with staff provides
      to be a valuable education tool, both for the residents and the staff. This
      learning strategy was adopted from UCSF Hospital and introduced to Nihon
      University Itabashi Hospital by K. Kumasaka MD in 1984. And that after 12 years
      of actual experience, we conclude the training program provides a readily
      available consultative service for the house staff, and facilitates patient care.
      In addition, we should make rounds with physicians and go to conferences in areas
      of interest and responsibilities. We could be mainly responsible for a number of
      problem-solving areas within the laboratory that would be directly responsive to
      patient problems encountered by physicians.

PMID- 9283222
TI  - [Clinical laboratory consultation in the general hospital].
AB  - The future of laboratory medicine depends not only on quality assurance but also
      on appropriate use of laboratory tests. The clinical laboratory consultation
      system is effective tool for clarifying purpose. As an active laboratory
      initiated consultation, we report patient-oriented "Laboratory Comment" on
      important or abnormal test results of each patient. About one thousand laboratory
      comments have been accumulated over the past eight years. From these comments, we
      discussed the requirements of laboratory consultation skills, establish standards
      for laboratory data check, and a database of reported and accumulated
      consultations or comments.

PMID- 9283223
TI  - [Consultation system in Tenri Hospital from a physician's perspective].
AB  - Tenri hospital is a large hospital with 1,001 beds, and is famous in Japan for
      its unique resident system. Two doctors and more than 120 technicians work in the
      department of clinical pathology. In this paper, the status of the consultation
      system in the field of clinical pathology is described from the perspective of a
      physician. Most physicians do not find it inconvenient to consult about
      laboratory tests and they come to know whom and how to consult. However, some new
      doctors sometimes have difficulties with consulting. As for residents, they can
      rotate in clinical pathology if they wish. All residents who rotated in each of
      the 4 divisions of clinical pathology said that their training was very useful.
      They did not learn procedures in depth because the period was short. However,
      they came to understand the entire departmental system, became acquainted with
      medical technologists and laboratory physicians, and could easily consult
      concerning laboratory tests. Communication and mutual understanding is a very
      important factor in consultation.

PMID- 9283224
TI  - [User's requests (from a practitioner's perspective)].
AB  - As a practitioner, I have to rely on outside clinical laboratories and affiliated
      hospitals to perform laboratory tests. In this abstract, I describe specific
      problems I have encountered with third-party laboratories, and propose solutions
      for these problems to optimize use of laboratory tests. BLOOD TESTS: The most
      frequent problem in ordering blood tests is the lack of detailed information
      regarding sampling conditions. I often have to call laboratories to check whether
      the sample should be serum or plasma, what volume is needed, whether the sample
      should be cooled, etc. I propose that clinical laboratories should provide
      practitioners' manuals that describe specific sampling information.
      ULTRASONOGRAPHY: Most laboratories do not keep the data from ultrasonographic
      tests. The lack of these is most problematic when test results are interpreted
      differently by laboratories and by practitioners. Retaining the data would also
      help private laboratories improve the quality of the test by enabling them to
      compare their interpretations with others'. ANNUAL MEDICAL SCREENING: Even if an
      abnormal finding is detected at medical screening clinics, the final diagnosis is
      usually not sent back to the screening facilities. This is highly recommended to
      establish an official system that mediates the feedback to screening centers.
      MRI: Due to miscommunication between practitioners and radiologists, the test is
      sometimes performed inappropriately. A thorough consultation should occur before
      the test to clarify specific goals for each patient. PATHOLOGICAL TESTS:
      Interpretation of results is often inconsistent among laboratories. Independent
      clinical laboratories tend to report results without indicating sample problems,
      while pathology departments at affiliated hospitals tend to emphasize sample
      problems instead of diagnosis or suggesting ways to improve sample quality.
      Mutual communication among laboratories would help standardize the quality of
      pathological tests.

PMID- 9283225
TI  - [An opinion from a user: a nurse's point of view].
AB  - The focus of this discussion is twofold; to provide an overview patient
      management in the nursing unit in relation to the Department of Examinations and
      to propose some strategies for assuring safe, accurate and effective laboratory
      tests from a nursing perspective. There are four issues identified as weaknesses
      in the environment of our collaboration; a lack of consistent support for anxious
      or frightened patients undergoing laboratory tests due to the low volume of
      information shared by us; a limited clinical laboratory consultation available to
      nurses because of unfriendly and unclear access to the Dept. of Examinations; a
      lack of collaboration and flexibility in responding to individual diversity in
      health problems; a lack of clinical laboratory coordination in scheduling
      laboratory tests, especially, for patients with multiple tests per day or per
      week. Based on those issues, five strategies are proposed. Greater involvement of
      medical technologists in routine laboratory works in the unit such as drawing
      blood and collecting specimens as needed. Clinical Laboratory tests except for
      urgent tests should be scheduled to minimize disturbances of life style for
      inpatients while waiting for the completion of all tests. An information
      processing system that helps nurses maintain advanced knowledge and skills is
      necessary to follow the state of art in the specialized area of clinical
      laboratory tests. It is definitely recommended that effective consultation be
      offered by the Dept. of Examinations. It is beneficial to patients for medical
      technologists to actively participate in the cooperative medicine of our hospital
      by sharing the patient's information with nurses in the unit. Lastly, it would be
      welcome to have direct communication with patients on the unit. This would
      facilitate mutual understanding between technologists and nurses. In conclusion,
      collaboration between the Department of Examinations and nurses of the unit may
      maximize patient benefits brought by the valuable information obtained from
      laboratory work through improved communication and mutual understanding.

PMID- 9283226
TI  - [Viral haemorrhagic fever].
AB  - Viral haemorrhagic fever denotes various kinds of febrile illness caused by
      certain viruses which often presents with bleeding tendency and occasionally
      shock. Out of these, the four maladies, Lassa fever, Ebola haemorrhagic fever,
      Marburg haemorrhagic fever and Crimean-Congo haemorrhagic fever which are
      endemically present in Africa or eastern Europe, are known to be such diseases
      with high man-to-man communicability. These four haemorrhagic fevers are,
      therefore, designated as special conditions requiring isolation during the period
      when the infected patients are shedding the viruses, not only in Japan but also
      in many other countries. We have so far only one such case of Lassa fever who
      returned to Japan from Sierra Leone in 1987. Some haemorrhagic fevers including
      dengue (haemorrhagic) fever and hantavirus infections (e.g. haemorrhagic fever
      with renal syndrome) are not known to be man-to-man transmissible and requiring
      no isolation. We have a number of dengue and dengue haemorrhagic fevers here in
      Japan today among imported febrile cases from tropical or subtropical countries.
      Every physician should take viral haemorrhagic fevers into consideration as one
      of the possibilities in diagnosing patients returning from overseas travel.

PMID- 9283227
TI  - [Evaluation of electrocardiographic left ventricular hypertrophy with both QRS
      voltage and ST-T change using echocardiography].
AB  - The purpose of the present study is to determine whether electrocardiographic QRS
      voltage criteria with ST-T change is useful in the diagnosis of left ventricular
      hypertrophy (LVH) using echocardiography. One hundred men including 59 with
      hypertension (HT), 9 with hypertrophic cardiomyopathy (HCM), and 32 without any
      cardiovascular disease were enrolled in this study. All of them had the
      electrocardiographic evidence of LVH by Sokolow-Lyon voltage criteria (RV5 or RV6
      > 2.6 mV, SV1+RV5 or SV1+RV6 > or = 3.5 mV). They were classified into three
      groups based on ST-T pattern as follows: Normal ST-T (group N): normal ST-T in
      twelve leads; Early strain ST-T (group ES): ST depression, flat T (T/R < 1/10),
      diphasic T or T wave inversion < 0.1 mV in V5 or V6; and Strain ST-T (group S):
      inverted T wave in V5 and V6. Echocardiographic LVH was determined when either
      interventricular septal thickness (IVST) or left ventricular posterior wall
      thickness (LVPWT) > or = 12 mm was present. According to this echocardiographic
      evidence, 31.7%(20/63) of group N, 75.0% (12/16) of group ES, and 100% (21/21) of
      group S were diagnosed. There were significant correlations between QRS voltage
      indices (RV5, RV6, SV1+RV5 and SV1+RV6) and IVST, (IVST+LVPWT)/2, and LV mass in
      group S(r = 0.650 to 0.858, p < 0.05) but not in group N. Values for IVST and LV
      mass were significantly greater in group S than in group ES or N. The
      electrocardiographic diagnosis of LVH with both QRS voltage and ST-T change thus
      appeared to be more useful than that with QRS voltage criteria alone.

PMID- 9283228
TI  - [Usefulness of transcranial magnetic stimulation in the objective assessment of
      therapy for adrenoleukodystrophy].
AB  - Adrenoleukodystrophy (ALD) is a hitherto untreatable, X-linked recessive disorder
      of the central nervous system characterized by the systemic accumulation of very
      long-chain fatty acids. Although various treatments have been proposed, objective
      evidence of their efficacy is insufficient. This is partly due to the absence of
      an appropriate method for evaluating the functions of the central nervous system
      (CNS). In this study, we took up the central motor conduction time (CMCT) as an
      index of the CNS functions, and measured it in two patients with ALD under
      steroid pulse therapy to know if this parameter is useful in assessing the
      effects of therapy. The right and the left motor cortex was stimulated separately
      with a MAGSTIM 200 magnetic stimulator, using a round coil of 9cm mean diameter
      to stimulate the hand area or a double cone coil to stimulate the leg area. CMCT,
      the time an impulse takes to travel from the motor cortex to the anterior horn
      cells in the corresponding region, was measured by a combination of transcranial
      magnetic stimulation (TMS) and F wave technique. Before treatment, CMCT to the
      cervical cord was prolonged slightly in both patients; CMCT to the lumbar cord
      was prolonged slightly in one and moderately in the other. After repeated steroid
      pulse therapy, a definite improvement, although partial and transient, was
      observed in either case. TMS thus seems to be useful not only for detecting
      functional derangement of the pyramidal tract but for evaluating the efficacy of
      therapy for this disease.

PMID- 9283229
TI  - [Effects of head-up tilting on vagal nerve activity in man].
AB  - OBJECTIVES: To evaluate the contribution of the vagal nerve activity in the
      cardiovascular postural adaptation, effects of decremental head-up tilting (90
      degrees, 64 degrees, 53 degrees, 44 degrees, 37 degrees, 30 degrees, 24 degrees,
      17 degrees, 12 degrees, 6 degrees and 0 degree) on time- and frequency-domain
      heart rate variability variables were analyzed in healthy young female.
      BACKGROUND: During head-up tilting, a hydrostatic venous pooling in the
      extremities occurs owing to gravity. To pump up the blood toward the upper body,
      the sympathetic nerve activity has been shown to play an important role. So, to
      date, few studies evaluated the effects of vagal nerve activity to stabilize the
      cerebral blood flow during head-up tilting. METHODS: Eight young female
      volunteers (age, 23.3 +/- 0.8 years; mean +/- SD) were evaluated. The
      electrocardiogram (ECG) by bipolar chest leads was recorded continuously during
      procedures, and the bed was tilted at 0.1 interval of sine function of tilting
      angle from upright position (90 degrees) to supine position (0 degree). The time
      domain measurements of cycle length variability (co-efficient of variance in
      percent for R-R intervals [CVRR], number of differences between adjacent R-R
      intervals that are > 50ms [RR50]) and the frequency domain measurements of low
      (0.08 to 0.15Hz, LF), high (0.15 to 0.40Hz, HF) and total (0.08 to 0.40, TF)
      power were performed to assess the cardiac sympathetic and vagal nerve activity.
      RESULTS: The CVRR showed no significant change during decremental head-up
      tilting, whereas the RR50 and the square root of HF power, more specific indices
      of cardiac parasympathetic tone, showed significant negative linear correlations
      to the sine of the tilting angle. In markers of cardiac sympathetic tone, there
      were significant positive correlations between the sine of the tilting angle and
      the normalized LF power or the LF-to-HF power ratio (LF/HF). CONCLUSION: These
      findings suggest that, in healthy young female, not only cardiac sympathetic
      nervous system but also cardiac vagal nervous system respond linearly to the
      change in body axis component of gravity, and they may contribute reciprocally
      and coordinately to cardiovascular postural adaptation.

PMID- 9283230
TI  - [A study on the role of ultrasonography in antenatal care in Thailand with focus
      on the appropriate technology].
AB  - The authors investigated the state of antenatal care, outcome of deliveries and
      use of ultrasonography at the Maternal and Childhood Health Hospital in Khonkane
      province, Thailand. The study was conducted before (stage I) and after (stage II)
      the introduction of the second ultrasonographic equipment in an attempt to set up
      a proper standard of technological level of clinical laboratory services and to
      investigate the usefulness of introducing ultrasonography into the prenatal care
      in developing countries. As a result, about 60% of first antenatal visits were in
      their second or third trimester, about 80% of pregnancies terminated by normal
      vaginal deliveries, parity, rate of cesareans sections and pre-term labors were
      not significantly different in both stages. Ultrasonography was performed on 16%
      of the first antenatal visits in stage I, while, in stage II, it was performed on
      31.3% of them. Ultrasonography was used most frequently to determine the
      gestational age and presentation of the fetus in both years (70.3% and 79.1%
      respectively in stage I and stage II). In most of the cases, ultrasonography was
      performed only once during the gestation. Thus, it was proved that technical
      training must be provided with introduction of new equipment to medical
      facilities and utilization of medical technologists for ultrasonography was
      another concern in developing countries. Beside, it was important to determine
      the proper period during the gestation when ultrasonography should be applied and
      to adopt an effective public health service including health education and health
      insurance to promote antenatal visits in time during the proper periods.

PMID- 9283231
TI  - [Blood amino acid levels in sarin poisoning patients].
AB  - Since plasma is generally employed for amino acid analysis, we compared amino
      acid levels in plasma with those in serum for healthy individuals and examined
      the influence of separation and storage conditions on the stability of the
      samples. Then, we determined the amino acid levels of frozen serum samples
      obtained from sarin poisoned patients. A. Comparison of Amino Acid Levels in
      Plasma and Those in Serum Blood was collected from 5 healthy individuals. Then,
      heparinated plasma and serum were separated by centrifugation immediately after
      blood collection. Serum was also separated by centrifugation after standing whole
      blood at room temperature for 1 hour. Frozen plasma and serum were store at -40
      degrees C for 5 months. All were subjected to analysis in an amino acid analyzer.
      It was found that the cystine (Cys) and 3-methyl-histidine (3-M-His) levels in
      serum and plasma were affected when stored in a frozen state, that the aspartate
      (Asp) level was changed according to the method of collecting serum, and that the
      taurine (Tau) and ornithine (Orn) levels were affected by standing blood. B.
      Analysis of Blood Taken from Sarin Poisoned Patients Twelve sarin poisoned
      patients were selected as subjects, and serum cholinesterase (Ch-E) and serum
      albumin (Alb) levels were determined. Amino acid analysis was conducted using an
      amino acid analyzer. Serum samples which had been obtained from the 6 patients
      and frozen and stored at -40 degrees C from 5 months were used for amino acid
      analysis. As a result, the serum Ch-E level decreased and the Alb level tended to
      rise. Since the Ch-E/Alb ratio was reduced in the sarin poisoned patients, it is
      considered useful for discrimination from liver cirrhosis in which both Ch-E and
      Alb levels decreased. Amino acid levels in the serum obtained from the sarin
      poisoned patients were compared with those of healthy individuals, both of which
      had been stored under the same conditions. There were significant differences in
      Asp, glutamate (Glu), phenylalanine (Phe), 3-M-His, glutamine (Gln), and Cys
      levels. The Glu, Phe, and Gln levels were not affected by storage of serum in a
      frozen state, while the Glu and Phe levels were elevated and the Gln level was
      reduced. Although Cys exhibited lower values in frozen serum samples, the Cys
      level was elevated with a rise in the serum Ch-E levels. Therefore, we deduced
      that Cys metabolism disorders also occur in sarin poisoning. As stated above, the
      Glu and Phe levels were elevated and the Gln and Cys levels were reduced,
      suggesting the presence of abnormal amino acid metabolism, in patients with sarin
      poisoning.

PMID- 9283232
TI  - [Clinical evaluation of RT-PCR method for detection of HCV-RNA--with special
      reference to Amplicor HCV].
AB  - Detection of the viral genome in serum is the most reliable way to analyze HCV
      viremia. In the present study, we evaluated the availability of a new detection
      kit for HCV-RNA, Amplicor HCV, which is based on the RT-PCR microplate
      hybridization protocol. The procedure of Amplicor HCV is simple, unlike the
      conventional RT-nested-PCR method. Although Amplicor HCV assay exhibited the
      lower sensitivity than the the conventional RT-nested-PCR method (10 x for HCV
      type 1a, 1b and 2b; 10(3) x for type 2a), Amplicor HCV assay could detect the HCV
      RNA in all HCV-RNA positive cases by conventional RT-nested PCR method, except
      for one case who contained low concentration of HCV-RNA (10 copies/ml). The
      coincidence rate was 99.2% in 120 clinical samples between two assays. Amplicor
      HCV assay, moreover, could efficiently evaluate the viremia regardless of anti
      HCV-2 antibody titer. This assay was useful for monitoring the effect of
      interferon therapy during and after administration. These results suggest that
      Amplicor HCV has an excellent availability for the clinical laboratories.

PMID- 9283233
TI  - [Transient hyperphosphatasemia observed in a boy with acute lymphoblastic
      leukemia].
AB  - A detailed time course of alkaline phosphatase (ALP; EC3.1.3.1) activity of
      transient hyperphosphatasemia (TH) in a 9-year-old boy with acute lymphoblastic
      leukemia (ALL) is described. The patient's serum ALP activity rose transiently to
      49 times the upper limit of normal adult, without any evidences of hepatic and
      bone disease. The half-life of ALP activity was calculated about 10 days. We
      characterized ALP isoenzymes by usual electrophoresis using cellulose acetate
      membrane (Titan III iso-vis) and polyacrylamide disc gel (AlkPhor), and
      isoelectric focusing using polyacrylamide slab gel. The former two methods showed
      typical two bands (fast-alpha 2 and alpha 2 beta bands) and the latter one method
      revealed more basic bands of liver and bone, suggesting the extensive
      sialylation. The patient complained fever and diarrhea. Enterococcus faecium was
      detected from his stool. Etiologically, two more patients in the same ward showed
      TH in the same period. It suggested TH would be occurred by infectious states.
      Awareness of such benign forms of hyperphosphatasemia not related to malignancy
      will aid the physician in the differential diagnosis of elevated ALP activity.

PMID- 9283234
TI  - [Eumycotic mycetoma of the lower leg].
AB  - Eumycotic mycetomas are extremely rare diseases in Japan. Only four cases have
      been reported. In the present report, eumycotic mycetoma of right lower leg of a
      44-year-old male of Thai origin, resident in Japan for more than five years, was
      presented. An induration was noticed on the antero-medial side beneath the knee.
      Computed tomography showed slightly high dense subcutaneous mass-like lesion at
      the medial side of the right tibia. Though no draining sinus was formed,
      histologic examination disclosed grains composed of septated hyphae with
      Splendore-Hoeppli material. Since more people from foreign countries tend to
      reside in Japan, physicians and pathologists should be aware of various
      infections which are not commonly found in Japan.

PMID- 9283235
TI  - [Profiles of effects of traditional oriental herbal medicines on central nervous
      systems in humans--assessment of saiboku-to and saiko-ka-ryukotsu-borei-to using
      EEG and pharmacokinetics of herbal medicine-derived ingredients as indices].
AB  - To elucidate usefulness of traditional oriental herbal medicines in psychiatric
      fields, we investigated their influences on central nervous systems in humans by
      using EEG and pharmacokinetics of herbal medicine-derived ingredients as the
      indices. The subjects were 12 healthy male volunteers who received single oral
      administration and after that received repeated oral administrations at a daily
      dose of Saiko-ka-ryukotsu-borei-to or Saiboku-to; EEG was recorded before
      administration, 1, 3, 6 hours and 10 days after administration. On direct
      comparison of global field powers calculated from 19-lead EEG before and after
      administration, it was verified that Saiboku-to possessed effects on central
      nervous systems. For assessment of pharmacokinetics of ingredients derived from
      Saiboku-to, pre- and post-treatment serum samples were assayed by HPLC and two
      ingredients were detected, besides individual differences being observed in their
      pharmacokinetic profiles. Given that these pharmacokinetics could be interpreted
      as the phenomena associated with Sho (traditional physical status classifications
      of patients), the subjects were classified into groups according to individual
      differences whereby quantitative pharmaco-EEG were employed to elucidate
      neurotropic effects of Saiboku-to. As the result, following two groups were
      evidenced: (1) a group demonstrating the mood elevator type after a single
      administration despite of no changes after repeated administrations, and (2) a
      group with a shift from the mood elevator type to the nootropics type being
      observed over time, delineating overt differences in EEG profiles among groups.
      Consequently, individual differences were evidenced to be involved in onset of
      neurotropic effects of Saiboku-to, permitting prediction of possible responses
      following repeated administrations by using EEG profiles. It was also suggested
      that neurotropic effects of respective ingredients could be anticipated by
      monitoring the time-course changes of both EEG and plasma levels of these
      ingredients. In summary, once further studies on oriental herbal medicines might
      progress based on efficacy assessments of respective ingredients with a clue of
      the present study, it is conceivable that these findings would play an important
      role as the objective indices in clinical application of herbal medicines in
      psychiatric fields, resulting in broadening the usefulness of oriental herbal
      medicines.

PMID- 9283236
TI  - [The delusion of theft in elderly with dementia--(1) Statistical data and
      psychopathology of the delusion].

PMID- 9283237
TI  - Immunosuppression--an overview.
AB  - The therapy of immune-mediated diseases in dogs and cats requires effective
      immunosuppressive therapy. The ideal therapy would suppress the abnormal (anti
      self) immune responses while leaving the normal (anti-pathogen) immune responses
      intact. Unfortunately, such a therapy is not readily available. Current
      therapeutic strategies designed to suppress aberrant immune responses include
      combinations of glucocorticoids, cytotoxic drugs, and other immunomodulating
      agents such as cyclosporine and androgens. Glucocorticoids have a multitude of
      effects on the immune response at several levels and are both antiinflammatory
      and immunosuppressive. Cytotoxic drugs such as cyclophosphamide and azathioprine
      suppress the immune response by inhibiting protein (ie, antibody) synthesis, DNA
      replication, and cell division. Some cytotoxic drugs cause lysis of
      immunocompetent cells. Cyclosporine A suppresses production of interleukin-2, a
      cytokine necessary for the amplification stages of the immune response and
      critical for the activation of both T and B lymphocytes. Androgens modulate the
      immune system by as yet poorly defined mechanisms involving alterations in
      lymphocyte numbers and function as well as mononuclear-phagocytic cell function.
      Newer immunosuppressive agents are being studied in laboratory animals and human
      transplant patients that either inhibit do novo synthesis of nucleotides or
      signal transduction in lymphocytes, thereby reducing the number or function of
      immunocompetent cells. These newer agents can be combined with more traditional
      therapies for enhanced immunosuppressive effects.

PMID- 9283238
TI  - Glucocorticosteroids as immunosuppressive agents.
AB  - When administered at pharmacological dosages, glucocorticosteroid hormones alter
      leukocyte kinetics, phagocytic cell function, cell-mediated immunity, and, to a
      lesser extent, humoral immunity. These properties are used to advantage in the
      treatment of immunologically mediated disease. Corticosteroids are used to
      suppress pathological immune responses associated with autoimmunity, inhibit
      rejection of allogenic tissues after organ transplantation, and to diminish
      inflammation associated with a wide variety of hypersensitivity disorders. The
      mechanisms by which corticosteroids relieve these conditions are still not
      completely understood but have recently become more comprehensible. By
      understanding how corticosteroids exert their effects, we can make better
      clinical decisions in the management of immune-mediated disease.

PMID- 9283239
TI  - The use of cytotoxic agents in the treatment of immune-mediated diseases of dogs
      and cats.
AB  - Cytotoxic drugs are often combined with glucocorticoids in the therapy of immune
      mediated diseases. Cyclophosphamide, azathioprine, chlorambucil, and methotrexate
      are cytotoxic drugs used most commonly for the purpose of immunosuppression.
      Cyclophosphamide and chlorambucil are alkylating agents, which cause cross
      linking of DNA resulting in altered protein production, decreased cell division,
      and cell death. Azathioprine and methotrexate are anti-metabolites, which cause
      inhibition of DNA synthesis and a cascade of other effects. These drugs, in
      general, are more effective if administered during the initial phases of disease
      when immunocompetent lymphocytes are in a phase of rapid proliferation. This is
      often impractical in the clinical situation and may explain therapeutic failures.
      This article focuses on the use of these drugs in the treatment of immune
      mediated diseases in dogs and cats and covers mechanisms of action, dosages, and
      side effects of individual cytotoxic agents.

PMID- 9283241
TI  - The use of danazol in the therapy of immune-mediated disease of dogs.
AB  - Currently available therapeutic protocols for immune-mediated diseases in dogs
      and cats can be associated with poor response rates and a high incidence of side
      effects. The development of multidrug protocols often results in a synergistic
      effect that more efficiently suppresses the immune response. One drug that may be
      added to other therapies is danazol, an androgen with immunomodulating
      properties. Androgens are known to suppress aberrant immune responses, and the
      fact that immune-mediated diseases are more common in females supports this.
      Danazol has been used in humans with immune-mediated hemolytic anemia and
      thrombocytopenia with some success. Danazol appears to reduce the binding of
      immuno-globulin and complement to the red blood cell or platelet surface and also
      may alter cytokine concentrations. The use of danazol in dogs with immunemediated
      hemolytic anemia and thrombocytopenia has been reported; however, the small
      number of animals evaluated make it difficult to assess its usefulness in
      veterinary medicine.

PMID- 9283240
TI  - Cyclosporine and tacrolimus.
AB  - Cyclosporine and tacrolimus are potent immunosuppressant agents that have been
      used extensively in humans, primarily for prevention of transplant rejection but
      also for the treatment of autoimmune disorders. Both agents have similar
      mechanisms of action and pharmacokinetic profiles. However, the expected toxicity
      of the agents is dissimilar. Although cyclosporine usage in veterinary medicine
      is limited, it has been used enough for therapeutic guidelines to be established.
      Tacrolimus, however, has undergone limited use in veterinary medicine. The drug
      is too toxic in dogs for its use to be recommended in most clinical situations.
      This article reviews the mechanism of action, pharmacokinetics, expected drug
      interactions and toxicities, and clinical usage of cyclosporine and tacrolimus in
      veterinary medicine.

PMID- 9283242
TI  - Therapeutic plasmapheresis.
AB  - Plasmapheresis is the process by which plasma containing components causing or
      thought to cause disease is removed from the circulation, and the remaining blood
      components are returned with plasma or a harmless plasma substitute to the donor.
      It primarily removes protein-bound solutes or high-molecular-weight solutes such
      as circulating protein-bound toxins, autoantibodies, immune complexes, or other
      abnormally occurring molecules. Plasmapheresis has been used in the treatment of
      more than 100 diseases in human medicine, including immune-mediated diseases,
      neoplasia, infectious diseases, sepsis, hyperlipidemia, thyrotoxicosis, and
      removal of toxins. In immune-mediated disease, it is most useful to rapidly
      decrease plasma concentrations of antibodies or immune complexes, whereas other
      immunosuppressive measures are used to prolong the effect.

PMID- 9283243
TI  - Human intravenous immunoglobulin therapy.
AB  - Human intravenous immunoglobulin (hIVIG) is a preparation of normal polyspecific
      IgG obtained from the plasma of healthy blood donors. Although purified
      immunoglobulins were initially developed for treatment of primary
      immunodeficiency syndromes, they have since been documented to be effective in
      the treatment of some immune-mediated diseases such as immune-mediated
      thrombocytopenia purpura and autoimmune hemolytic anemia. Blockade of Fc
      receptors on mononuclear phagocytic cells has been proposed as the most likely
      mechanism for the rapid early response to hIVIG treatment. Human IVIG has been
      used to treat canine immune-mediated hemolytic anemia (IMHA), anemia with
      myelofibrosis, and immune-mediated thrombocytopenia. Doses from 0.5 to 1.5 g/kg
      may be effective, although most studies have used a dose of 1 g/kg. Human IVIG is
      administered as an intravenous infusion over 6 to 12 hours, and dogs should be
      carefully monitored for adverse reactions during administration. The possibility
      of a increased risk of thromboembolism should be considered when undertaking
      hIVIG treatment. The safety of multiple treatments of hIVIG has not been
      established. In most dogs with IMHA, benefit may be limited to short-term
      improvement in hematocrit, which may allow time for other treatment modalities to
      become effective. Dogs with nonregenerative anemia and associated myelofibrosis
      may have longer-term responses to hIVIG treatment.

PMID- 9283244
TI  - Immunotherapy and cytokines.
AB  - Immunomodulation is now possible in veterinary medicine with the licensure of a
      number of biological products by the United States Department of Agriculture for
      veterinary use. These products activate primarily macrophages, induce the
      production of cytokines, and have various effects on the activity and
      proliferation of B and T lymphocytes. Those products most commonly used are
      inactivated whole bacteria of Propionibacterium acnes, cell wall fractions of
      nonpathogenic Mycobacterium spp, and the lysate derived from lysis of
      Staphylococcus aureus by a bacterial phage. All products have been licensed for
      use against specific diseases, but the literature includes studies for off-label
      usage. These immunomodulators are considered to be nonspecific stimulators of the
      immune system and may affect both humoral and cellular functions of immunity.

PMID- 9283245
TI  - Genetic immunotherapy for cancer.
AB  - The application of gene therapy to the treatment of human and veterinary diseases
      offers an innovative addition to the clinician's treatment options. Gene therapy
      can potentially be used to (1) replace defective or missing genes, (2) treat
      cancer, and (3) deliver drugs. The focus of this paper is the use of gene therapy
      in the treatment of cancer. To be effective, genes must be delivered to target
      cells which can then serve as the factory to produce the gene product. Delivery
      systems include retroviral vectors, adenoviral vectors, and direct introduction
      of plasmid DNA into cells. In the case of cancer immunotherapy, introduced genes
      produce products that enhance tumor immunosurveillance and tumor cell killing by
      immune mechanisms.

PMID- 9283246
TI  - Vaccine adjuvants.
AB  - Vaccine adjuvants provide enhanced immune responses to a variety of antigens.
      Unlike human vaccines that are limited to aluminum-based adjuvants, veterinary
      vaccines may contain a large number of substances either alone or in combination
      that act as vaccine adjuvants. Although the use of adjuvants in veterinary
      vaccines enhances the immunogenicity of vaccines, they have been responsible for
      a number of side effects. This article explores the rationale of currently used
      vaccine adjuvants and some of the adverse events associated with their use in
      veterinary medicine.

PMID- 9283247
TI  - Nutritional modification of inflammatory diseases.
AB  - Regulation of the immune system is extremely complex. We are only starting to
      understand how the immune system coordinates the body's response to a disease or
      invading pathogen. Immunomodulation, as the term implies, can be used to
      designate either a suppression or an augmentation of an immune response.
      Suppressing the function of the immune system may be important in cases of
      inflammation and augmenting the immune response when increased resistance to
      disease is required. Nutrition does and can play an important role in modulation
      of the animal's immune system. The majority of scientific literature published on
      the interaction of nutrition and the immune system correlates the effects of
      nutrient deficiency and modulation of an immune response. These studies have
      evaluated deficiencies of protein; energy; the fat soluble vitamins A, D, and E;
      the B-complex vitamins; vitamin C; and the minerals selenium, iron, zinc, and
      copper and their relationship to immune dysfunction. Most recently, researchers
      have concentrated efforts on evaluating the impact specific fatty acids have on
      modulation of the immune system. Undoubtedly, the nutritional status of the
      animal plays an important role in resistance mechanisms against disease causing
      organisms and may influence the outcome of disease in infected animals. The focus
      of this chapter is to concentrate on the role specific polyunsaturated fatty
      acids have on the immune response of animals and to consider the potential for
      nutritional modification of diseases related to inflammation.

PMID- 9283249
TI  - [Screening for Chlamydia trachomatis?].

PMID- 9283248
TI  - Peptostreptococcal myonecrosis of extraperitoneal origin--a life-threatening
      complication of pelvic ring disruption.
AB  - This report illustrates the clinical and pathological findings of anaerobic
      streptococcal myonecrosis following extraperitoneal rectal injury in a 28-year
      old patient with traumatic pelvic ring disruption. Four days following admission,
      the patient underwent laparotomy, debridement and drainage of the left-sided
      abdominal wall and presacral space for gross surgical emphysema and streptococcal
      anaerobic myonecrosis. The specificity of this infection and its impact on the
      diagnosis and treatment of the condition are briefly discussed. Accent is given
      to early recognition, appropriate medical and surgical management, and hyperbaric
      oxygenation as an additive measure.

PMID- 9283250
TI  - Legionnaires' disease in Europe, 1996. Introduction.

PMID- 9283251
TI  - Monkeypox in the Democratic Republic of the Congo (former Zaire).

PMID- 9283252
TI  - Rural medicine: it's come a long way.

PMID- 9283253
TI  - Encouragement of partnering with non-physician clinicians hurts physician
      members.

PMID- 9283254
TI  - Nurse practitioners cannot replace physicians.

PMID- 9283255
TI  - Farm injuries don't just involve farmers.

PMID- 9283256
TI  - Changes in agriculture bring potential for new health and safety risks.

PMID- 9283257
TI  - Marshfield Clinic'c role in primary care and rural health in Wisconsin.

PMID- 9283258
TI  - Rural EMS: who are you and what do you need?

PMID- 9283259
TI  - Physicians' responsibility to assess patients' ability to operate a motor
      vehicle.

PMID- 9283261
TI  - Domestic abuse: complicated by rural living.

PMID- 9283262
TI  - University of Wisconsin agricultural safety and health activities.

PMID- 9283260
TI  - Life in the country: physicians discuss practicing in rural Wisconsin.

PMID- 9283263
TI  - Cancer screening and prevention in rural Wisconsin: the Greater Marshfield
      Experience.
AB  - BACKGROUND: Providing medical services to rural residents results in unique
      challenges to providers and patients. Cancer screening (CS) and early detection
      services (EDS) are frequently underutilized with rural residents often presenting
      with advanced cancer at diagnosis. A comprehensive approach to determine barriers
      and overcome them constitutes "The Greater Marshfield Experience." METHODS: Focus
      groups with rural residents determined the greatest barriers to receipt of CS and
      EDS were distance, cost, time from work and self-reliant behavior. Directives to
      address these concerns were to keep information simple and provide services at
      the workplace. In response, Marshfield Clinic and its research division developed
      a collaborative research partnership with public health agencies (PHA), federally
      funded government programs and volunteer agencies. RESULTS: In-house activities
      to remove barriers for providing CS and EDS included the development of a
      separate screening unit for these activities. Reminder systems were employed to
      notify patients of the need and availability of preventative services. Co
      payments for health screening services were eliminated from the clinic owned
      health plan. Area residents near poverty level were encouraged to enroll in
      federally subsidized health plans that promoted and paid for CS and EDS.
      Federally funded cancer screening studies were implemented that funded breast and
      cervical cancer screening and evaluated the benefits of screening for prostate,
      lung, colorectal and ovarian cancers (PLCO). Outreach activities included
      developing partnerships with local PHA and minority groups and providing mobile
      screening services to remote areas. CONCLUSION: Concentrated, collaborative
      efforts to develop in-house systems and outreach activities resulted in delivery
      of CS and EDS in remote areas.

PMID- 9283264
TI  - Serum potassium levels in Caucasian and Hmong patients in Wausau, WI, October,
      1996.

PMID- 9283265
TI  - What's new in microbiology ... emerging infections.

PMID- 9283266
TI  - The medical outcomes research project Low Back Pain Study.

PMID- 9283267
TI  - Update on informed consent law: the Johnson V. Kokemoor decision.

PMID- 9283268
TI  - Informed consent: advice from the trenches.

PMID- 9283269
TI  - If a little knowledge is a dangerous thing, what about a lot of knowledge: what
      have we learned from Pandora?

PMID- 9283270
TI  - The Human Genome Project and women.

PMID- 9283272
TI  - The Human Genome Project and breast cancer.

PMID- 9283271
TI  - An overview of the Human Genome Project and its implications for women.

PMID- 9283273
TI  - Genetic accountability and pregnant women.

PMID- 9283274
TI  - Genetic counseling and women.

PMID- 9283275
TI  - Policy implications of the Human Genome Project for women.

PMID- 9283276
TI  - Gender justice in genetics.

PMID- 9283278
TI  - In quest of the perfect analogy for using in vitro fertilization patients as
      oocyte donors.
AB  - Whether painted in totalitarian terror, like the organ farm story and The
      Handmaid's Tale, the science-fiction reality of Make Room! Make Room!, the cinema
      noir urban tragedy of prostitution, or the portrayals of slavery (Afro-American,
      Nazi-European, and Russian), this series of resemblances, I hope, illustrates the
      power of analogy to surface sensitivity to ethical issues in the efficient, and
      possibly entertaining, texture demanded by medical personnel. Although my quest
      was quixotic from the start, I hope that this exercise will encourage your
      consideration of using analogy as an educational tool to heighten the awareness
      in medical personnel to many issues, to allow our better service of patients and
      society.

PMID- 9283277
TI  - Defining and measuring unintended pregnancy: issues and concerns.
AB  - This article of the past and current measures of unintendedness of pregnancy has
      been offered in the hope that investigation into this area can be expanded.
      Current information available from available national surveys is not comparable
      due to different survey questions, inclusion criteria, and timing of interviews.
      What are often reported as rates of unintendedness may be rates of unwantedness-
      a completely different concept. Many studies fail to delineate the distinction
      between those unintended pregnancies that are indeed unintended versus those that
      were mistimed. Potentially, these existing data sets could be reanalyzed by using
      specific inclusion criteria for unintendedness, maternal age, and marital status.
      This information might be helpful in improving the comparability between the
      surveys and in assessing trends in unintendedness. In the future, to accurately
      measure unintendedness of pregnancy, we must use a consistent definition that
      takes into account the complexities of the issue. Valid and reliable scales that
      reflect the value of unintendedness from the mother's perspective need to be
      developed to reflect the potential change in intendedness over time. The adequate
      measurement of unintendedness of pregnancy is the first step in addressing the
      Healthy People 2000 goal and measuring progress in addressing the nation's
      reportedly high rate in the long-term goal of addressing the risk factors of
      unintended pregnancy.

PMID- 9283281
TI  - Learning to ask about domestic violence.

PMID- 9283279
TI  - Women's health education for medical students: an interdisciplinary response.

PMID- 9283280
TI  - Experience and acceptability of medical abortion with mifepristone and
      misoprostol among U.S. women.

PMID- 9283282
TI  - Evaluation of an HIV/AIDS education program in an urban prenatal clinic.

PMID- 9283283
TI  - An immunological approach to the evaluation of welfare in Holstein Frisian
      cattle.
AB  - Clinical immunological and haematological parameters, along with clinical
      conditions and growth rate, were studied in 413 male Holstein Frisian calves
      introduced into a large centre for genetic selection in different seasons of the
      year. Abnormalities were revealed by the laboratory tests in the great majority
      of calves after transportation stress, a general tendency to the restoration of
      physiological values being evident thereafter. Laboratory parameters were highly
      correlated with disease conditions: with three exceptions only, animals showed
      altered laboratory parameters some days before the occurrence of clinical
      symptoms. Eighteen per cent of animals showed altered laboratory parameters with
      no obvious clinical signs of disease; yet they experienced a reduced weight gain.
      Results suggest that clinical immunological and haematological parameters could
      be the foundation of a new, large-scale, robust approach to the control of
      welfare in cattle, which should be integrated preferably by a further range of
      records and measures.

PMID- 9283285
TI  - Antimicrobial sensitivity in microorganisms isolated from canine otitis externa.
AB  - It is important to test the antimicrobial sensitivity of the aetiological agents
      of otitis externa before starting treatment in order to prevent the development
      of antibiotic resistance in the microorganisms. In this study the sensitivity
      patterns in bacteria and yeasts isolated as aetiological agents from otitis
      externa were analysed. Antifungal and antibacterial activity tests were done
      using the automated system ATB Fungus and the classic diffusion test
      respectively. The azole compounds had the greatest antifungal properties, while
      beta-lactams had the strongest antibiotic activity. This study reflects the
      increasing importance of sensitivity tests in chronic otitis externa due to the
      increasing antimicrobial resistances in bacteria and yeasts. If it is necessary
      to initiate an empiric treatment before the results of the antimicrobial test,
      the application of miconazole or econazole for yeasts and oxacillin or
      amoxicillin-clavulanic acid against bacteria is recommended.

PMID- 9283284
TI  - In vivo and in vitro detection of canine distemper virus nucleoprotein gene with
      digoxigenin-labelled RNA, double-stranded DNA probes and oligonucleotides by in
      situ hybridization.
AB  - A single-stranded RNA, two double-stranded (ds) DNA probes and 10
      oligonucleotides labelled with digoxigenin were comparatively evaluated for their
      usefulness to detect canine distemper virus (CDV) nucleoprotein RNA in in vitro
      infected Vero cells and in tissues of dogs with spontaneous CDV infection by in
      situ hybridization (ISH). In addition, results were compared to CDV nucleoprotein
      antigen distribution as demonstrated by immunohistochemistry. The RNA probe was
      derived from the virulent A75/17 strain, the DNA and oligonucleotide probes from
      the avirulent Onderstepoort strain of CDV. The two DNA probes were 287 and 126
      base pairs long. For ISH, various factors including fixatives, proteolytic
      digestion, probe concentration, hybridization conditions and detection systems
      were compared. All probes were suitable for demonstration of CDV RNA in in vitro
      infected cells, regardless of the CDV strain employed. In vivo CDV nucleic acid
      was detected by RNA and the dsDNA probes. However, the probes varied
      substantially with respect to sensitivity and specificity. The CDV RNA probe was
      far superior in sensitivity when compared to the DNA probes. Furthermore, the
      shorter DNA probe displayed a higher sensitivity, indicating that length of the
      probe is an important parameter when selecting probes. Oligonucleotides displayed
      only rarely a positive signal and caused frequently hybridization signals in the
      nucleus, which where considered not specific for CDV. Summarized, the present
      study reveals that RNA probes are currently the most sensitive tool for detection
      of CDV RNA in tissues.

PMID- 9283286
TI  - Coagulase-negative staphylococcal intramammary infections in cows and heifers
      during the nonlactating and periparturient periods.
AB  - Coagulase-negative staphylococci (CNS) are isolated frequently from unbred and
      primigravid heifers and from lactating and nonlactating dairy cows. The
      importance of CNS intramammary infections that occur during the nonlactating
      period has not been adequately delineated. Mammary secretions from udders
      infected with CNS during early lactation and the nonlactating period have
      increased somatic cell counts, CNS have been isolated in mammary secretions from
      cows with clinical mastitis, and a few studies have indicated that CNS infected
      mammary glands produced significantly less milk during lactation than uninfected
      mammary glands. In addition, mammary glands of postpubertal heifers infected with
      CNS were not as well developed as uninfected mammary glands. Consequently, CNS
      intramammary infections in heifers and cows during the nonlactating period could
      impair mammary gland growth and development and ultimately influence mammary
      function during lactation resulting in decreased lactational performance. Some
      CNS IMI detected in heifers and multiparous cows at calving do not persist into
      early lactation. Postmilking teat disinfection with an effective germicide and
      antibiotic therapy during the nonlactating period markedly reduces the prevalence
      of CNS in dairy herds. Methods of controlling CNS infections in primigravid
      heifers based on prepartum intramammary antibiotic therapy have been developed,
      and results have shown that prepartum antibiotic therapy is very effective
      against CNS and other mastitis pathogens as well. Additional research is required
      to determine the influence of CNS infections that occur during the nonlactating
      period on milk yield in the subsequent lactation.

PMID- 9283288
TI  - Passive protection of specific pathogen free chicks against infectious bursal
      disease by in-ovo injection of semi-purified egg-yolk antiviral immunoglobulins.
AB  - In order to develop an experimental model for passive immunity in SPF chickens,
      active neutralizing immunoglobulins (Ig) directed against infectious bursal
      disease virus (IBDV) were extracted from the yolk of eggs laid by conventional
      layers immunized against IBDV. Concentrated Ig extracts were inoculated via the
      intra-vitellin route into 7-day-old embryonated SPF hen eggs. Although
      detrimental to hatchability, Ig inoculation resulted in hatching two series of
      SPF chicks with passive immunity against IBDV. The neutralizing and ELISA
      antibody titres at 1 day-old (respectively 12.64 and 13.15 log2; and 4915 and
      4277), the kinetics of decay of the anti-IBDV antibodies and the protection
      afforded by passive antibodies against highly virulent IBDV challenge proved
      highly consistent with data previously reported on conventional chicks. In-ovo
      inoculation of purified egg-yolk immunoglobulins may hence be a good experimental
      model for anti-IBDV maternally-transmitted immunity. This experimental model
      might possibly be adapted to other pathogens or vaccines for which interference
      with maternally derived antibodies is a matter of concern at 1 day-old.

PMID- 9283287
TI  - Treatment of bovine mastitis with houttuynin sodium bisulphate.
AB  - Houttuynin sodium bisulphate (HSB), alpha hydroxyl-capryl-ethyl-sodium
      sulphonate, is a product formed by reacting sodium bisulphate with houttuynin,
      which is obtained from a medicinal herb Houttuynia cordata Thunb. From HBS an
      aqueous intramammary solution was made for the treatment of bovine clinical
      mastitis. A total of 104 acute and subacute mastitis cases were randomly assigned
      into two groups with 52 cases in each group: 1. an HSB group in which 80 mg HSB
      was infused into an affected gland; and 2. a PS group in which intramammary
      administration of 800,000 i.u. penicillin G in combination with 1 g of
      streptomycin (PS) was conducted. The treatments were administered twice daily
      until the inflammatory signs were eliminated and mammary secretion became normal.
      In acute mastitis, 88.2% (15 of 17) were clinically cured and 52.9% (nine of 17)
      microbiologically cured by HSB; in the PS group, 90.0% (18 of 20) were clinically
      cured and 55.0% (11 of 20) microbiologically cured. In subacute cases, the
      clinical and microbiological cure rates were 94.3% (33 of 35) and 45.7% (16 of
      35) respectively, in the HSB group; and in the PS group the clinical and
      microbiological cure rates were 93.7% (30 of 32) and 43.8% (14 of 32),
      respectively. No statistically significant difference was found between HSB and
      PS groups in the treatment of acute as well as subacute mastitis. In addition, an
      inhibitory effect was found on the growth of lactic streptococcus in the milk
      collected within 48 h of intramammary treatment with penicillin G in combination
      with streptomycin. However, for HSB, a mild inhibitory effect on lactic
      streptococci was detected in the milk within 12 h of treatment.

PMID- 9283290
TI  - Topological chirality of iron-sulfur proteins.
AB  - An examination of x-ray structures of single-cluster [4Fe-4S] proteins in the
      Protein Data Bank has revealed that all redox proteins and the glutamine 5
      phosphoribosyl-l-pyrophosphate amidotransferase from Bacillus subtilis have a
      topological configuration arbitrarily designated as D, whereas the DNA repair
      enzyme endonuclease III from Escherichia coli has the opposite topological
      configuration L. This is the first example in which both senses of topological
      chirality have been observed in a class of proteins.

PMID- 9283289
TI  - DNA-binding studies of XSPTSPSZ, derivatives of the intercalating heptad repeat
      of RNA polymerase II.
AB  - The synthesis, solution conformation, and interaction with DNA of three 8-residue
      peptides structurally related to the heptad repeat unit found at the C-terminus
      of RNA polymerase II are reported. Peptides QQ, XQ, and PQ are derived from the
      parent sequence YSPTSPSY (peptide YY), which was reported to bind to DNA by
      bisintercalation [M. Suzuki (1990) Nature, Vol. 344, pp. 562-565], and contain
      either a 2-quinolyl (Q), 2-quinoxolyl (X), or 5-phenanthrolyl (P) group in place
      of the aromatic side chains of the N- and C-terminal tyrosine residues present in
      the parent sequence. The combined results of linear dichroism and induced CD
      measurements of peptides QQ, XQ, and PQ with calf thymus DNA are consistent with
      weak binding of the peptides to DNA in a preferred orientation in which the
      chromophores are intercalated. Small increases in the melting temperatures of
      poly[d(A-T)2] are also consistent with the peptides interacting with DNA. While
      enzymatic footprinting with DNase I showed no protection from cleavage by the
      enzyme, chemical footprinting with fotemustine showed that the peptides modify
      the reactivity of the major groove, presumably via minor groove binding. Peptide
      QQ inhibited fotemustine alkylation significantly more than either XQ or PQ, and
      slightly more than YY. In aqueous solution, nmr experiments on QQ, XQ, and PQ
      show a significant population of a conformation in which Ser2-Pro3-Thr4-Ser5 form
      both type I and type II beta-turn conformations in equilibrium with open chain
      conformations. Nuclear magnetic resonance titration experiments of PQ with
      (GCGTACGC)2 showed small changes in chemical shifts, consistent with the
      formation of a weak nonspecific complex. Analogous experiments, using peptides QQ
      and XQ with (GCGTACGC)2, and peptide YY with (CGTACG)2, showed no evidence for
      the interaction of the peptides with these oligonucleotides. These results show
      that peptides of general structure XSPTSPSZ are weak nonspecific DNA binders that
      differ significantly from previously characterized S(T)PXX DNA-binding motifs
      that are generally AT-selective minor groove binders.

PMID- 9283291
TI  - Synthesis, conformation, and biological activity of two fMLP-OMe analogues
      containing the new 2-[2'-(methylthio)ethyl]methionine residue.
AB  - The new C alpha-tetrasubstituted alpha-amino acid residue 2-[2'
      (methylthio)ethyl]methionine (Dmt) has been introduced into the reference
      chemotactic tripeptide HCO-Met-Leu-Phe-OMe (fMLP-OMe) in place of the leucine or
      methionine, respectively. The biological activity of the new analogues [Dmt2]fMLP
      OMe (2) and [Dmt1]fMLP-OMe (3) has been determined; whereas 2 is active toward
      human neutrophils, stimulating directed migration, superoxide anion generation,
      and lysozyme release, 3 results practically inactive in all tested assays. A
      conformational analysis on 2 and 3 has been performed in solution by using ir
      absorption and 1H-nmr. The conformation of 2 was also examined in the crystal by
      x-ray diffraction methods. Both 2 and 3 adopt fully extended conformation in
      correspondence with the Dmt residue. Biological and conformational results are
      discussed and compared with related previously studied models.

PMID- 9283292
TI  - The foldability landscape of model proteins.
AB  - Molecular evolution may be considered as a walk in a multidimensional fitness
      landscape, where the fitness at each point is associated with features such as
      the function, stability, and survivability of these molecules. We present a
      simple model for the evolution of protein sequences on a landscape with a
      precisely defined fitness function. We use simple lattice models to represent
      protein structures, with the ability of a protein sequence to fold into the
      structure with lowest energy, quantified as the foldability, representing the
      fitness of the sequence. The foldability of the sequence is characterized based
      on the spin glass model of protein folding. We consider evolution as a walk in
      this foldability landscape and study the nature of the landscape and the
      resulting dynamics. Selective pressure is explicitly included in this model in
      the form of a minimum foldability requirement. We find that different native
      structures are not evenly distributed in interaction space, with similar
      structures and structures with similar optimal foldabilities clustered together.
      Evolving proteins marginally fulfill the selective criteria of foldability. As
      the selective pressure is increased, evolutionary trajectories become
      increasingly confined to "neutral networks," where the sequence and the
      interactions can be significantly changed while a constant structure is
      maintained.

PMID- 9283293
TI  - Comparisons of the conformational biases imposed by trans-2,3-methanomethionine
      and alpha-methylmethionine.
AB  - A comparative study of four peptidomimetics of the sequence Phe-Met-Arg-Phe-amide
      (FMRFa) was performed to compare the conformational bias caused by trans-2,3
      methanomethionine and alpha-methylmethionine stereoisomers. The specific
      compounds studied were {(2S,3S)-cyclo-M} RFa, F{(2R,3R)-cyclo-M} RFa, F{(S)-alpha
      Mem} RFa, and F{(R)-alpha-MeM} RFa. Molecular simulations based on CHARMm 22
      indicate that gamma-turn, inverse gamma-turn, and alpha-helical conformations
      about the cyclo-M residue are accessible to the two F{cyclo-M} RFa stereoisomers.
      Similar calculations for F{(S)-alpha-MeM} RFa, and F{(R)-alpha-MeM}RFa indicate
      that the alpha-methylamino acids tend to favor alpha-helical conformations. The
      nmr data is presented for the four peptidomimetics. Most informative were the
      rotating frame nuclear Overhauser effect cross peaks between the NH protons
      proximal to the methionine surrogates, and the C beta hydrogens. Overall, these
      nmr data indicate F{(2S,3S)-cyclo-M} RFa and F{(2R,3R)-cyclo-M} RFa
      preferentially adopt inverse gamma-turn and gamma-turn conformations,
      respectively, whereas F{(S)-alpha-MeM} RFa and F{(R)-alpha-MeM} RFa tend to form
      partial left- and right-handed helical structures (although energy differences
      between the two turn structures, and between the two helical structures are
      likely to be small). It is suggested that the wider NH-C alpha-CO angle of
      cyclopropane amino acids and their more severe steric requirements around the C
      beta carbons force the peptidomimetic N- and C-termini into the same region of
      conformational space. This favors C7 turns in the cyclopropane amino acid series
      relative to the less constrained alpha-methyl derivatives.

PMID- 9283294
TI  - Comparison of hard-cylinder and screened Coulomb interactions in the modeling of
      supercoiled DNAs.
AB  - A 1000 base pair (bp) model supercoiled DNA is simulated using spherical screened
      Coulomb interactions between subunits on one hand and equivalent hard-cylinder
      interactions on the other. The amplitudes, or effective charges, of the spherical
      screened Coulomb electrostatic potentials are chosen so that the electrostatic
      potential surrounding the middle of a linear array of 2001 subunits (31.8 A
      diameter) closely matches the solution of the nonlinear Poisson-Boltzmann
      equation for a cylinder with 12 A radius and the full linear charge density of
      DNA at all distances beyond the 24 A hard-core diameter. This superposition of
      spherical screened Coulomb potentials is practically identical to the particular
      solution of the cylindrical linearized Poisson-Boltzmann equation that matches
      the solution of the nonlinear Poisson-Boltzmann equation at large distances. The
      interaction energy between subunits is reckoned from the effective charges
      according to the standard DLVO expression. The equivalent hard-cylinder diameter
      is chosen following Stigter's protocol for matching second virial coefficients,
      but for the full linear charge density of DNA. The electrostatic persistence
      length of the model with screened Coulomb interactions is extremely sensitive to
      the (arbitrarily) chosen subunit length at the higher salt concentrations. The
      persistence length of the hard-cylinder model is adjusted to match that of the
      screened Coulomb model for each ionic condition. Simulations for a superhelix
      density sigma = -0.05 using a spherical screened Coulomb interaction plus a 24 A
      hard-cylinder core (SCPHC) potential indicate that the radius of gyration of this
      1000 bp DNA actually undergoes a slight increase as the NaCl concentration is
      raised from 0.01 to 1.0M. Thus, merely softening the potential from hard-cylinder
      to screened Coulomb form does not produce a large decrease in radius of gyration
      with increasing NaCl concentration for DNAs of this size. Radii of gyration,
      static structure factors, and diffusion coefficients obtained using the
      equivalent hard-cylinder (EHC) potential agree well with those obtained using the
      SCPHC potential in 1.0M NaCl, but in 0.1M NaCl the agreement is not as good, and
      in 0.01M NaCl the agreement is definitely unsatisfactory. These conclusions
      differ in significant respects from those obtained in previous studies.

PMID- 9283295
TI  - Secondary structure induction in aqueous vs membrane-like environments.
AB  - The conformational propensity of the 20 naturally occurring amino acids was
      determined in aqueous 3-[N-morpholino]propane-sulfonic acid (MOPS) buffer,
      protein interior-like [nonmicellar sodium dodecylsulfate (SDS)] and membrane-like
      environments (micellar SDS and lysophosphatidylglycerol/lysophosphatidylcholine
      micelles) using a single "guest" position in a polyalanine-based model host
      peptide (Ac-KYA13K-NH2). This model system allows the intrinsic alpha-helical or
      beta-sheet propensity of the amino acids to be determined without intra- and
      interchain side chain interactions. The overall environment dependence observed
      for the conformational propensity for the amino acids studied confirms the
      importance of determining propensity in lipidic environments to better elucidate
      the biological functions of proteins. The hydrophobic interactions between
      peptide side chains and lipids appeared to be the primary forces driving the
      conformational induction in lipidic environments of the model peptides studied.
      Finally, when comparing the results of these studies with those reported in the
      literature, the local environment was found to highly influence 65% of the 20
      naturally occurring amino acids.

PMID- 9283296
TI  - Mild head injury in children and adolescents: a review of studies (1970-1995).
AB  - In this article, the authors provide a comprehensive review of the research of
      mild head injury in children and adolescents from 1970 to 1995. Because of marked
      variability in methodologies across studies, a preliminary box-score tally was
      computed, without regard to studies' scientific or methodological merit. These
      results revealed 13 adverse, 18 null, and 9 indeterminate findings related to
      neuropsychological, academic, or psychosocial outcome. When studies were
      classified based on methodological merit, the stronger studies were generally
      associated with null outcomes across domains. However, a few of the less stronger
      neuropsychological studies (5 of 40) reported subthreshold and transitory
      alterations during the early postinjury period. At the present time, cautious
      acceptance of the null hypothesis is recommended until more definitive studies
      are conducted that address the problems raised in this review.

PMID- 9283297
TI  - Assessment of depression in patients with brain pathology: the case of stroke.
AB  - The assessment of depression in patients with brain pathologies--a topic of
      considerable clinical and research interest--is complicated by a variety of
      factors. Among the most problematic are cognitive consequences of brain injury
      that can diminish the reliability and validity of information used to diagnose
      depression, determine its severity, ascertain its predictors, and evaluate its
      impact. In this article, the authors examine the challenges to depression
      assessment in patients who have had a stroke, the neurologically impaired
      population in which it has been most frequently studied. Focusing on poststroke
      depression research, they describe methodological limitations that may contribute
      to conflicting outcomes and conclusions and offer suggestions for improving the
      specificity, consistency, validity, and reliability of assessment methods and
      procedures when investigating depression in patients with brain pathologies.

PMID- 9283299
TI  - Outcome, attrition, and family-couples treatment for drug abuse: a meta-analysis
      and review of the controlled, comparative studies.
AB  - This review synthesizes drug abuse outcome studies that included a family-couples
      therapy treatment condition. The meta-analytic evidence, across 1,571 cases
      involving an estimated 3,500 patients and family members, favors family therapy
      over (a) individual counseling or therapy, (b) peer group therapy, and (c) family
      psychoeducation. Family therapy is as effective for adults as for adolescents and
      appears to be a cost-effective adjunct to methadone maintenance. Because family
      therapy frequently had higher treatment retention rates than did nonfamily
      therapy modalities, it was modestly penalized in studies that excluded treatment
      dropouts from their analyses, as family therapy apparently had retained a higher
      proportion of poorer prognosis cases. Re-analysis, with dropouts regarded as
      failures, generally offset this artifact. Two statistical effect size measures to
      contend with attrition (dropout d and total attrition d) are offered for future
      researchers and policy makers.

PMID- 9283298
TI  - The role of immaturity in human development.
AB  - The possibility that infants' and young children's immature behaviors and
      cognitions are sometimes adaptive is explored and interpreted in terms of
      evolutionary theory. It is argued that developmental immaturity had an adaptive
      role in evolution and continues to have an adaptive role in human development.
      The role of developmental retardation in human evolution is discussed, followed
      by an examination of the relation between humans' extended childhood and brain
      plasticity. Behavioral neoteny, as exemplified by play, is examined, as are some
      potentially adaptive aspects of infants' perception and cognition that limit the
      amount of information they can process. Aspects of immature cognition during
      early childhood that may have some contemporaneous adaptive value are also
      discussed. It is proposed that viewing immaturity as sometimes adaptive to the
      developing child alters how children and their development are viewed.

PMID- 9283300
TI  - What do nurses feel about end of life decisions?

PMID- 9283301
TI  - Creating a new brand of mental health nurse.

PMID- 9283303
TI  - Establishing a protocol for parental presence in recovery.
AB  - This study aimed to contribute to providing a quality service that is sensitive
      to the needs of children undergoing surgery and their parents. An action research
      approach, focusing on parents' perceptions of coming into recovery, was used. A
      retrospective survey design was utilized to establish parents' views. A response
      rate of 71% (n = 100) was achieved. A short prospective study carried out
      concurrently achieved a 50% (n = 50) response from questionnaires handed out in
      recovery. Almost all the parents (98%) from both studies felt that they and their
      child had benefited from the parents' presence in recovery. When given the
      choice, 100% of parents came to recovery. The structural location and information
      given to parents preoperatively helped to ensure that parents were easy to find
      when the time was right to come to recovery. Communication between recovery
      staff, children and parents before surgery was recognized as a significant
      factor. A protocol for allowing parents into the recovery room has been produced.
      Staff who had preconceived ideas about parents' presence now identified the
      practice as good and considered that it contributed to the quality of the
      service.

PMID- 9283302
TI  - Complications of allergies to latex urinary catheters.
AB  - Latex products are widely used both in our homes and in hospitals. Latex allergy
      is an increasingly worrying problem for health professionals, not least allergy
      to latex urinary catheters. The pathophysiology of latex allergy is discussed
      with reference to catheter allergy. Other known problems of latex catheters are
      also highlighted, including toxicity leading to urethritis and stricture
      formation, and encrustation. Nurses need to be aware of the increasing incidence
      of latex allergy and the importance of screening patients specifically for this
      risk factor.

PMID- 9283305
TI  - The biology of dementia due to Parkinson's disease.
AB  - This article is one of a series focusing on dementias due to an underlying
      biological factor. The reader should refer to the previous articles in the series
      (Delieu and Keady, 1996a,b). This article focuses on the normal structures within
      the brain which are involved in motor control and describes what occurs when this
      system is disrupted by an inappropriate reduction in the neurotransmitter
      dopamine. In time, this reduction in dopamine may have deleterious effects on
      other neuronal systems within the central nervous system, namely the diminished
      acetylcholine neurones which may lead to a dementional state. Possible causes of
      Parkinson's disease are discussed and some treatments briefly outlined.

PMID- 9283306
TI  - Managing patients suffering from acute and chronic fatigue.
AB  - The subjective experience of fatigue is common and debilitating, and affects many
      individuals in various healthcare settings. The condition requires adequate
      assessment, innovative planning and interventions, and patient-centred
      evaluations by the nursing profession. Fatigue, whether acute or chronic, needs
      to be recognized as a true and valid condition in order for treatment to be
      successful. There are many considerations to be taken into account when working
      with the fatigued, and this article suggests how the areas needing most attention
      may be tackled. Chronic fatigue and acute fatigue can be quite different
      conditions, requiring different approaches, of which nurses need to be aware. In
      order to reduce the effects of fatigue on the client, nurses need to fully
      understand the factors surrounding the phenomenon of fatigue to provide expert
      care, to help educate the patient, and improve the quality of life.

PMID- 9283307
TI  - Putting Working Paper 10 into practice: education and training.
AB  - Education and training: working Paper 10 (WP10) (Department of Health (DoH),
      1989a) may prove to be another example of policy implementation whereby the needs
      of nurse education will be dominated yet again by service demands for greater
      resources. Alternatively, there are indications that it could result in the most
      significant change in nurse education since the 1949 Nurse Registration Act. Over
      the last 7 years, there has been relatively little discussion about WP10 in the
      nursing press. The aim of this article, therefore, is to evaluate the impact of
      WP10 on nurse education, highlighting the reasons for its inception and
      discussing its main proposals. The author examines the issues that have arisen
      from its implementation so far, and those which may emerge in the future.

PMID- 9283304
TI  - Expanding the role of the neonatal transport nurse: nurse-led teams.
AB  - Nottingham neonatal service provides a unit-based interhospital transport
      programme for the stabilization and transportation of critically III neonates
      within the Trent region. The transport nurse is responsible and accountable for
      providing optimum care for infants in conjunction with a registrar. The quality
      of care received by the neonate requiring emergency transfer could be further
      enhanced by a team of two specifically trained transport nurses.

PMID- 9283308
TI  - The ABC of committee work 2: How meetings are conducted.
AB  - The first part of this article looked at the roles of the officers in a
      committee. This second part illustrates for nurses how committee meetings should
      be conducted. Rules govern the way meetings are announced and who may be present.
      The opening and closing of meetings need to be properly defined and conducted.
      Most committee meetings adopt the same agenda format. General conduct and the
      order of business are equally universal but latitude is exercised in less formal
      committees. Awareness of proper committee procedures makes it much more
      comfortable and satisfying to participate in meetings.

PMID- 9283309
TI  - Alternating-pressure air mattresses: the Quattro range.
AB  - Alternating-pressure air mattresses (APAMs) have a long history, and after some
      advances in their design, which began in the 1980s, have become widely used for
      pressure sore prevention. A recent variation in the inflation/deflation cycle of
      a 'large-cell' APAM, which allows the use of lower (peak) pressures for inflating
      the air cells, is used in the Quattro range of APAMs. This should make the new
      products more comfortable, more versatile, and more durable than earlier large
      cell APAMs. This article discusses both the theoretical and practical advantages
      and disadvantages of these products. It also suggests a simple method of checking
      the suitability of a given support for promoting a healthy skin for highly
      dependent patients.

PMID- 9283310
TI  - The importance of voting in the UKCC elections.

PMID- 9283311
TI  - Children are receiving inadequate care in A&E.

PMID- 9283312
TI  - Evaluating the success of clinical supervision.

PMID- 9283313
TI  - A nurse-led clinic for patients with peripheral vascular disease.
AB  - Patients with peripheral vascular disease have complex and challenging health
      needs. This article describes an innovative nurse practitioner role in the
      provision of care for patients with intermittent claudication in an acute
      hospital setting. A small-scale evaluative study of patient satisfaction with the
      nurse consultation revealed high levels of satisfaction with the care received.
      It is suggested that experienced nurses can make substantial contributions to
      improving care for patients with chronic disease.

PMID- 9283314
TI  - Efficacy of cardiac rehabilitation 2: Smoking and behaviour modification.
AB  - The first part of this article (Vol 6(12): 697-702) critically reviewed the
      research on the acclaimed beneficial effects of a number of cardiac
      rehabilitation programmes including exercise, stress management and educational
      interventions. This article will examine empirical studies on the efficacy of
      smoking cessation and type A behavioural modification programmes. Lamentably, few
      studies have been conducted on the efficacy of smoking cessation. Caution is
      indicated when establishing conclusions from studies on type A behaviour given
      the conceptual problems of this construct, i.e. its inability to consistently
      predict coronary heart disease, evidence of confusion surrounding the improper
      use of the psychometric measures and the neglect of salient psychosocial baseline
      variables. A number of clinical implications and future directions for research
      are indicated.

PMID- 9283315
TI  - Understanding memory to enhance nursing practice.
AB  - A key aspect of compliance is that the advice given is remembered. Nurses who
      have an understanding of human memory processes are better in formed to offer
      healthcare advice to their patients and may do so in such a way that it is more
      likely to be remembered. They can also enhance their own memory to promote job
      performance and enhance study skills. This article demonstrates that human memory
      is an active information-processing activity. The processes of registration,
      storage and retrieval are explained, and recommendations are made on how an
      awareness of memory function can be used to improve practice.

PMID- 9283316
TI  - Drug administration in day centres for people with learning disabilities.
AB  - A study was made of the problems associated with the need to administer medicines
      at day centres for people with learning disabilities. In Leicestershire, 167
      (13%) of 1317 people with learning disabilities who attended day centres required
      the administration of medicines. The percentage of attenders requiring drug
      administration varied from day centre to day centre (minimum 4%, maximum 23%).
      Antiepileptics were the most commonly administered drugs, followed by
      antipsychotics. The administration of medicines took up a significant amount of
      time for senior members of the day centre staff and had a great potential for
      errors. In only 32 cases was it deemed essential that the drug administration
      occurred at the day centre.

PMID- 9283317
TI  - 'Getting in touch' with people with severe learning disabilities.
AB  - This article explores innovative and interactive ways of working with people who
      have severe learning disabilities, special needs and/or challenging behaviour
      who, despite the efforts of those who support them, are not able to respond to
      attempts to interact with them. It examines the possibilities of communicating by
      using people's own behaviours and outlines how these methods of interaction can
      be developed into a 'language' which people with these disabilities recognize and
      find motivating. Entering into a person's world in a way that is not confusing or
      threatening may allow him/her to move from solitary self-stimulation to shared
      activity. People with these disabilities will then become aware of a world
      outside their own (sometimes they are aware of this but are unable to make a
      connection between what they perceive and themselves), and begin to understand
      their relationship to it. Surprise is an important element as it shifts attention
      from the inner space to the source of the intervention. A number of examples
      illustrate a range of person-centred approaches and the variety of disabilities
      that may be assisted.

PMID- 9283318
TI  - Pressure sores: counting the legal cost of nursing neglect.
AB  - In Vol 4(22): 1298-9, the author discussed the Audit Commission's (1995) report
      on coordinating care for elderly patients which found serious lapses in the way
      pressure sore prevention is carried out. This article discusses recent legal
      cases and complaints made to the Health Service Commissioner or Ombudsman
      regarding pressure sores. It focuses on case reports and complaints. These are
      useful educational tools which illustrate the problems in this area and the steps
      needed to improve the quality of care. The conclusion reached is that most
      pressure area complaints and cases could have been easily avoided at minimum or
      no expense.

PMID- 9283319
TI  - Can data collection during the grieving process be justifiable?
AB  - Research has shown that there are a number of competing theories regarding the
      use of bereaved people for research purposes. One view emphasizes their
      vulnerability, weakness and inability to take part in decision-making. Another is
      that there is an infringement of rights if people are denied the freedom of
      choice to take part in research. This article considers issues concerned with
      data collection from recently bereaved relatives who were at some stage of the
      grieving process. The participants were interviewed as part of the OXMIS study
      which aimed to identify the incidence of myocardial infarction in Oxfordshire. A
      total of 142 interviews took place (59 home visits and 83 telephone interviews).
      Of the cases not interviewed, sufficient information was gained in 94% from other
      sources to fulfil the required criteria. The perceived benefit or apparent risk
      of vulnerable groups participating in research is discussed in light of the study
      results.

PMID- 9283320
TI  - The ABC of committee work. 1: Officers, members and their duties.
AB  - Many nurses will be asked during their career to serve on a committee but will
      have little concept of the work and procedures involved. This article, the first
      of two parts, describes the work of the officers and members of a committee. The
      chairperson controls meetings according to rules which make for the smooth and
      equitable running of the committee. The secretary, who has to work closely with
      the chairperson, is often more experienced regarding the rules and can do
      valuable work in guiding the chairperson. Normally, the secretary's job includes
      duties before, during and after meetings. A treasurer looks after the financial
      affairs of any committee which holds a budget. The vice-chairperson is the
      natural successor of the chairperson and should be groomed to take the chair.

PMID- 9283321
TI  - Medical investigations. 7: Colposcopy.

PMID- 9283323
TI  - Of pedestals, pedagogues and podiums.

PMID- 9283322
TI  - What has happened to morale in nursing?

PMID- 9283324
TI  - Changes in burn patient care.
AB  - Little has changed in the care of patients with burns for many years but nurses
      are now becoming involved in the introduction of innovative treatments. This
      article introduces relevant information about two of these products; cerium
      nitrate-sliver sulphadiazine (Flammacerium) and Integra, a new form of
      'artificial skin'.

PMID- 9283325
TI  - The role of the nurse anaesthetist: a survey of theatre nurses' views.
AB  - This article reports on the views of theatre nurses on the role of the nurse
      anaesthetist, which has received recent attention in the context of changing
      nursing and medical roles. 168 nurses working in 5 major operating departments
      were asked by way of questionnaire, for their views on nurse anaesthetists. 103
      responses were received with 57 (55.3%) in favour of the development and 46
      (44.7%) against. F and G grade nurses were found to be more favourable about
      nurse anaesthetists than their junior colleagues. In view of these findings,
      further investigation and discussion, notably with the medical profession and
      clinical managers, is recommended. The author believes that this proposed
      development must be given due thought and serious consideration before any
      attempts to introduce it are made.

PMID- 9283326
TI  - Perioperative communication in a multicultural society.

PMID- 9283327
TI  - Conference and study day reports.

PMID- 9283328
TI  - PC heaven Part--6. Healthy computing.

PMID- 9283329
TI  - 'Just tell me .... which knob do I press to cancel the alarm?'.

PMID- 9283330
TI  - African diary.
AB  - You may have been wondering why there have been no further installments of
      African Diary. The short answer is that Diana was very ill from the side-effects
      of anti-malaria drugs. She has been back in this country being treated and having
      a spell of rest and recuperation. You will remember that Diana and Colin, her
      husband, had left Mozambique and were very busy building up a new mission
      station, funded by a business man from Liverpool, in Uganda. Before being taken
      ill, Diana had written some notes for the Journal which will be enough for two
      more articles. Diana and Colin have not yet decided whether they will return to
      Africa but we have told Diana how Journal readers enjoyed reading her news. We
      wish her well for the future.

PMID- 9283332
TI  - Bereavement.

PMID- 9283333
TI  - The role of the urology nurse specialist.

PMID- 9283334
TI  - Standards for the management of swabs, needles and instruments in the operating
      theatre.
AB  - The management of swabs, needles and instruments in the operating theatre is a
      high-risk and problem-prone area for the operating theatre nurse. The purpose of
      this research is to formulate specific standards on the management of swabs,
      needles and instruments in the operating theatre to ensure the safety of the
      patient. An exploratory and descriptive research design was used and executed in
      3 hospitals of a private hospital group in Gauteng. A structured two phase
      process was followed, i.e. the development phase and the validation phase. This
      last phase was done by means of deliberate debate. It is recommended that these
      standards be implemented, tested and validated on a national basis and a
      monitoring and evaluation system should be developed to ensure nursing compliance
      with these standards.

PMID- 9283335
TI  - The use of action research as an appropriate method of introducing and evaluating
      change in nursing care in an accident & emergency unit in Durban--Part 2.
AB  - This 2-part article discussed firstly in Curationis 19.3 this year, the general
      characteristics of action research, compares several strategies of approach and
      describes the author's chosen method of applying action research to particular
      aspects of nursing care in an Accident & Emergency Unit in a Durban hospital.
      This second part describes identification of problems within the unit, the
      implementation of change and the limitations and potential of such study to
      nursing practice.

PMID- 9283336
TI  - A study of clinical performance of nurses who recently completed the
      comprehensive basic nursing course.
AB  - A study was conducted to assess clinical performance of registered nurses who had
      recently completed the new comprehensive basic nursing course. This regional
      project was undertaken because of controversy surrounding clinical competence of
      the graduates/diplomates of the new regulation course. Senior qualified nurses
      gave their views according to Likert Scale statements and open-ended questions.
      Findings were that the sample was of the opinion that clinical performance of the
      new graduates/diplomates falls short of expectations.

PMID- 9283337
TI  - [A study of the attainment of program objectives of the 4-year diploma course].
AB  - A descriptive survey was undertaken to determine the the extent to which the
      programme objectives for the Diploma in Nursing Leading to Registration as a
      Nurse (General, Psychiatric, Community) and Midwifery are being met.
      Questionnaires were completed by diplomates and nursing service managers. Various
      problem areas regarding realization of the programme objectives were identified.

PMID- 9283338
TI  - Focus group interview as a data gathering tool: its application to nurses'
      understanding of HIV infection and AIDS.
AB  - The focus group interview (FGI) is a research method not commonly used by nurses.
      It is an effective method if qualitative data are needed and may be used
      independently to get indepth information, but also can be used in conjunction
      with tools such as questionnaires, to elicit information that could not be
      gathered otherwise. For the FGI to be applied correctly the researcher must be
      well versed with its contents, and ensure that the primary reason for using such
      a method is solely to collect data. Other reasons like decision-making or
      reaching a consensus would not be appropriate. The researcher has shown how this
      method was used in a study in a specialised hospital in Durban which examined
      professional nurses' knowledge and understanding of AIDS and HIV infection. The
      results not only illustrated knowledge and understanding, but raised sensitive
      issues and dilemmas related to caring for HIV infected patients. Areas of further
      research were highlighted and recommendations made.

PMID- 9283339
TI  - An investigation into the attitude of professional nurses towards euthanasia.
AB  - The purpose of the study was to identify professional nurses attitudes towards
      euthanasia. A descriptive study of the attitudes of professional nurses towards
      euthanasia was undertaken. The data collecting instrument was a questionnaire,
      which was self-administered to 26 professional nurses working in different wards.
      The majority of professional nurses were against euthanasia in hospitals. It was
      also evident that professional nurses need to be involved in decision making on
      euthanasia. Though professional nurses revealed negative attitudes towards
      euthanasia, there are situations in which they felt passive euthanasia was
      necessary.

PMID- 9283340
TI  - Indigenous healers in the North West Province: a survey of their clinical
      activities in health care in the rural areas.
AB  - The purpose of this study was to explore the clinical conditions brought to
      indigenous healers by people in the rural areas in search of health care. The
      demographic variables and preventive, promotive, curative and follow-up
      activities of indigenous healers were investigated. Data were collected from a
      simple random sample of 35 indigenous healers. A questionnaire designed by Mogoba
      (1984) for investigation of training and functioning of traditional doctors in
      Southern Africa was modified and used to collect data. Findings showed that
      indigenous healers deal with the same health problems confronting formal health
      workers, especially in the paediatric field. Infertility, mental illness problems
      and sexually transmitted diseases ranked high in the adult conditions brought to
      the healers. There seem to be conditions that can be handled only by the
      indigenous healers due to their cultural nature. Findings also show that the
      services of indigenous healers are not confined to any specific group or social
      class within black population.

PMID- 9283341
TI  - Nurses in action--an introduction to Action Research in nursing.
AB  - Action Research is one of the new generation of qualitative research methods in
      the social sciences which has special significance for nurses in South Africa.
      The collaborative, participative and reflective qualities of Action Research
      appeal to practitioners, and lend themselves to joint problem solving activities
      in local contexts. This paper sets out a rationale for Action Research, then
      describes its features, strengths, and limitations, Ways of overcoming the latter
      are suggested. The paper concludes that Action Research has potential
      applications in the field of nursing, not only for the purposes of practical
      problem solving, but also for improving the personal and professional practice of
      nurses, and for emancipating nurses from their subordinate position in the
      hierarchy of health science.

PMID- 9283342
TI  - Codependency: a concomitant field of interest in research into the phenomenon
      caring.
AB  - The growing popularity of caring is evident throughout the nursing profession.
      Research into the phenomenon caring, however, necessitates that caring as an
      ethic be distinguished from pseudo caring actions and experiences. Codependence
      and codependency are proposed as being of a pseudo-caring nature. Research
      interest into this field of study needs to be kindled.

PMID- 9283343
TI  - Adapt or die?
AB  - The worldwide economic recession and the concomitant limited stock of finances
      have had an influence on the available money of every household and have also
      inhibited the improvement of socio-economic conditions and medicine. The
      Reconstruction and Development Programme (RDP) has the objective of improving the
      living conditions of the people with regard to housing, education, training and
      health care. The latter seems to be a major problem which has to be addressed
      with the emphasis on the preventive and promotional aspects of health care. A
      comprehensive health care system did not come into being property in the past
      because of the maldistribution of health care services, personnel and differences
      in culture and health care beliefs and values. The question that now arises, is
      how to render a quality health care service within the constraints of inadequate
      financing and resources. A comprehensive literature study has been done with
      reference to quality health care and financing followed by a survey of existing
      health services and finances. Recommendations are made about minimum requirements
      to be accepted if one were to adapt rather than die in terms of the provision of
      healthcare: the decentralization and rationalization of the administration of
      health care, the stress on and realization of effective and efficient primary
      health care, the acceptance of participative management in health providing
      organizations, the provision of financial management training for health care
      managers and the application of management accounting principles for the
      improvement of the efficiency and effectiveness of management.

PMID- 9283344
TI  - The implications of culture shock for health educators: reflections with Barer
      Stein.
AB  - Culture shock is an intensely personal universal human experience that may emerge
      in any cross cultural social encounter. Therefore, it may be deduced that culture
      shock is an experience that may occur in all spheres of life in which individuals
      are confronted by world views and life styles that differ from their own whether
      in terms of health, education or occupation amongst others. It is a situation
      that calls for adaptation or adjustment on the part of the individual. This
      article explores the relationship between culture shock and culture adaptation as
      an aspect of learning which has been developed by Thelma Barer-Stein. Stress is
      laid on the role of the individual, as health educator, and the choices must make
      if he/she is to gain an understanding of the community in which he/she serves and
      to attribute new meanings to the situation by which he/she is confronted.

PMID- 9283345
TI  - A formative model for student nurse development and evaluation--Part 1-
      Developing the model.
AB  - Preparing student nurses for the profession is a complex task for nurse
      educators; especially when dealing with the development of personal and
      interpersonal skills, qualities and values held in high esteem by the nursing
      profession and the community they serve. These researchers developed a model for
      formative evaluation of students by using the principles of inductive and
      deductive reasoning. This model was implemented in clinical practice situations
      and evaluated for its usefulness. It seems that the model enhanced the standards
      of nursing care because it had a positive effect on the behavior of students and
      they were better motivated; the model also improved interpersonal relationships
      and communication between practising nurses and students. The fact that students
      repeatedly use the model as a norm for self evaluation ensures that they are
      constantly reminded of the standards required of a professional nurse.

PMID- 9283346
TI  - [Knowledge and attitude of nursing students concerning AIDS in 3 educational
      institutes of the West Cape].
AB  - A survey was done by means of a questionnaire to obtain information on the
      knowledge and attitudes of 297 nursing students from three training institutions
      in the Western Cape regarding HIV-infection and AIDS-patients. Results indicated:
      The average knowledge regarding AIDS scored 72.5% They generally had a positive
      attitude regarding the caring for AIDS-patients; 81% of the junior and 54% of the
      senior students were of opinion that their training were inadequate while 91.5%
      of the respondents held the opinion that the training hospital must provide more
      training. It is recommended that the curricula of training institutions make
      adequate provision for relevant training regarding AIDS.

PMID- 9283347
TI  - Quality improvement in health care--a fundamental analysis and South African
      perspective.
AB  - This article is based on the opening address that was delivered at a national
      conference with the launching of the South African Society for Quality in Health
      Care (SASQuaH). The quality improvement process and principles are analyzed, as
      well as an exposition of the South African situation. The concepts regarding
      quality, quality improvement and quality assurance are clarified, the different
      stakeholders in formalised quality improvement explained, as well as the motives
      for and principles of quality improvement in health services. The different
      external and internal mechanisms in quality improvement are analyzed, including
      the principle of community ownership and international collaboration. Continuous
      development and capacity building regarding quality improvement is recommended at
      all levels of health service delivery.

PMID- 9283348
TI  - [Facilitation of respect for rights and responsibilities of people by student
      nurses].
AB  - Events such as strikes by nurses presently focus the attention on human rights in
      health care. During the four year training of the student nurse leading to
      registration the tutor should facilitate the development of respect for rights
      and responsibilities of people. The purpose of this study was to determine the
      extent to which respect for rights and responsibilities of people are facilitated
      with the student nurse, as well as to set guidelines for facilitating respect for
      rights and responsibilities in nursing education practice. A qualitative,
      contextual, exploratory, descriptive study was done at a nursing school. The
      literature concerning rights and responsibilities in health care was explored
      using a conceptual framework from which 10 categories related to rights and
      responsibilities were identified. These categories served as a guideline for the
      data analysis throughout the study. The inclusion of rights and responsibilities
      in the microcurricula of the nursing school were explored and described using
      content analysis. By means of a focus group interview and analysis of the
      transcription of the interview, the lecturers were used as a data source to
      describe how the concepts of rights and responsibilities were taught in practice.
      Subsequently, the respect for rights and responsibilities of people by the fourth
      year students was explored and described. Students were asked to write naive
      sketches about written scenario's of hypothetical situations from the clinical
      practice. After comparing the data from the four sources final interpretations
      were made concerning the extent to which respect for rights and responsibilities
      of people are facilitated with the student. Both facilitating factors and
      limitations were identified. From the interpretations nine guidelines with
      possible ways of operationalisation were set for nursing education.

PMID- 9283349
TI  - Health seeking behaviour by Cape-Townians: a mini-research by first year student
      nurses at a college for nursing in Cape Town.
AB  - The author was asked by a student nurse to use South African examples when
      teaching, as the text books were either American or English, and they wanted
      sociology that applied to their own environment. In the next year of teaching the
      prescribed objectives concerning "Health Seeking Behaviour", it was suggested
      that the students question the populace, and find out for themselves how South
      Africans behaved when they thought they were ill. By doing this it was hoped that
      it would also give deeper insights into the meaning people attributed to
      illness/sickness.

PMID- 9283350
TI  - Canadian Nurses Association Policy Statement. The comprehensiveness of Canada's
      health care system.

PMID- 9283351
TI  - Reaching out: marketing strategies for organ donation awareness.

PMID- 9283352
TI  - An intervention supporting end stage renal disease treatment option decisions.

PMID- 9283353
TI  - ED patients deserve the "work" of nursing.

PMID- 9283354
TI  - Houston fire department pioneers latex-free prehospital environment.

PMID- 9283355
TI  - A trauma patient with sickle cell anemia.

PMID- 9283356
TI  - A survey of violence toward nursing staff in one large Irish Accident and
      Emergency Department.
AB  - INTRODUCTION: Nurses in Ireland are increasingly concerned about the escalating
      incidence of verbal and physical abuse, particularly in Accident and Emergency
      (A&E) Departments. This first detailed survey of violence in A&E departments in
      Ireland was conducted at St. James's Hospital, Dublin, the largest hospital in
      the Republic of Ireland. The aims of the survey included determining the
      following factors: (1) what proportion of staff had experienced physical or
      verbal violence while on duty in the hospital, (2) the frequency of such attacks,
      (3) whether the violence was officially reported and sick leave taken, (4)
      whether age and experience changed attitudes to violence, or the reporting of it,
      and (5) the level of staff training, if any, in dealing with violence. METHODS: A
      wide-ranging questionnaire was designed and confidentially offered to nurses and
      attendants (patient care assistants). Standard definitions of physical and verbal
      violence were framed. RESULTS: Of 36 nurses on staff, 27 responded; nine of 13
      attendants responded. Doctors were not included because only one is a permanent,
      non-contract employee. The responding nurses ranged in experience from newly
      qualified to senior nurses and unit managers with more than 15 years A&E service.
      The survey found that half of the nurses had been assaulted physically, or
      verbally, one third within the past 12 months. Only two of the 27 respondent
      nurses were not worried about being physically assaulted--both were psychiatric
      trained male nurses and neither had ever been assaulted. Most verbal abuse was
      not reported--despite availability of an official report book--and 29% of nurses
      had not even reported their last physical assault. The likelihood of reports of
      verbal violence being made increased with age and experience. Staff criticised
      hospital managers, the police, and the courts for their attitude about assaults
      on nurses. Respondents believed assaults on nurses were treated less seriously
      than similar incidents involving private citizens. DISCUSSION: The results of
      this study mirrored those of similar surveys in Britain and the United States.
      Nonreporting was revealed as a major problem, whereas reporting violence was
      often seen as an empty gesture because of a lack of institutional support for the
      nurse/attendant victims. Staff reported feeling vulnerable to abuse and there was
      a general desire for training in self-protection. Since the survey was first
      presented to hospital managers, St James's Hospital has made a number of changes
      to improve staff security. These include teaching staff breakaway techniques,
      increasing the number of security officers on duty, issuing personal alarms, and
      encouraging staff to officially report all incidents.

PMID- 9283357
TI  - Impact of an education program about domestic violence on nurses and doctors in
      an Australian emergency department.
AB  - OBJECTIVE: To increase the knowledge of nurses and doctors in an emergency
      department about the topic of domestic violence; to change any negative practices
      and attitudes toward victims; to increase knowledge of the referral processes for
      psychosocial aspects of domestic violence; and to increase knowledge of community
      resources for domestic violence victims. METHODS: Identical knowledge, attitude,
      and practice surveys were conducted with nurses and doctors in an emergency
      department before and after an educational intervention program about domestic
      violence. A matched-pair analysis of those respondents who answered both pretest
      and posttest surveys was conducted to measure the impact of the program on nurses
      and doctors. RESULTS: Nurses and doctors had a reasonable knowledge of the topic
      of domestic violence before the education program (correct answers: nurses,
      61.6%; doctors, 63.4%). However, the program had a positive impact on their
      knowledge (correct answers posttest: nurses, 71.5%; doctors, 72.4%), with more
      significant changes for nurses than for doctors. The program affected both
      nurses' and doctors' attitudes (of 10 positive attitudinal statements: pretest,
      7.9; posttest, 8.6). On both the pretest and posttest, nurses and doctors did not
      subscribe to a number of the myths about domestic violence that have been
      described in the domestic violence literature. These findings should be treated
      with caution because of the low response rates to the surveys from doctors
      (28.0%, n = 20) and nurses (53.0%, n = 48). DISCUSSION: Further research is
      needed into the beliefs and practices of nurses and doctors about domestic
      violence. The impact of this education program highlights the necessity for
      introducing training programs for health professionals on domestic violence
      problems.

PMID- 9283358
TI  - A comparative study of hematocrits drawn from a standard venipuncture and those
      drawn from a saline lock device.
AB  - BACKGROUND: Most trauma patients in the emergency department have multiple
      hematocrits drawn to monitor hypovolemia. These venipunctures are painful to the
      patient and frustrating for hospital staff when venipuncture sites are difficult
      to locate. PURPOSE: The purpose of this study was to determine whether the
      hematocrit values of blood samples obtained with saline lock devices agree or are
      different from those blood specimens obtained by standard venipuncture. If they
      agree, can the traditional venipuncture route of blood collection be replaced by
      collection from a saline lock device? METHODS: The study used a
      quasiexperimental, repeated measures design. The research was conducted at a
      teaching, regional level I trauma center with annual ED visits of 65,000. Each
      subject had hematocrit samples obtained by venipuncture (control) according to
      standard trauma protocols. Within 5 minutes of obtaining each control specimen, a
      hematocrit sample was obtained with a saline lock device (experimental) after a 5
      ml discard volume was obtained. RESULTS: Results were analyzed by measures of
      central tendency and paired t test. There were no differences in mean hematocrit
      values in blood obtained by saline locks (41.1 +/- 4.4) and those drawn from
      direct venipunctures (41.0 +/- 3.9). CONCLUSIONS: Obtaining samples for
      determination of hematocrit values from a saline look device is an accurate
      method of obtaining serial hematocrit values.

PMID- 9283359
TI  - Different presentations of cocaine intoxication: four case studies.

PMID- 9283360
TI  - The ED nurse practitioner: pearls and pitfalls of role transition and
      development.

PMID- 9283361
TI  - A rural community hospital's experience with family-witnessed resuscitation.

PMID- 9283362
TI  - Carlos Doe, "just a drunk".

PMID- 9283363
TI  - Interfacility transfer form--COBRA-wise and user-friendly.

PMID- 9283364
TI  - Guide to finding pediatric injury prevention public education materials.

PMID- 9283365
TI  - Syrup of ipecac: appropriate use in the emergency department.

PMID- 9283366
TI  - "Shopping" for EMS protective clothing.

PMID- 9283368
TI  - The need for quick computer response with minimal input: development of an ED
      computer system.

PMID- 9283370
TI  - This nurse educator is "hooked on humor".

PMID- 9283371
TI  - Emergency medical services for children.

PMID- 9283373
TI  - Consent and confidentiality in the care of the sexually assaulted adolescent.

PMID- 9283367
TI  - The development of an educational outreach program by one aeromedical service.

PMID- 9283372
TI  - Warm blankets and p values: philosophy and science coming together.

PMID- 9283374
TI  - Management of severe head injury: new document provides guidelines. Brain Trauma
      Foundation.

PMID- 9283375
TI  - A 72-year-old woman with a hip fracture.

PMID- 9283376
TI  - Nurse's office, health office, or clinic? The importance of a name and a piece of
      real estate.

PMID- 9283377
TI  - Mental health in schools: expanded opportunities for school nurses.
AB  - Emerging trends are reshaping the work of school nurses and other school service
      personnel. With respect to direct service and consultation, school nurses
      increasingly are called upon to deal with psychosocial and mental health
      problems. Beyond that, school nurses must continue to actuate their roles as
      advocates, catalysts, brokers, and facilitators of the type of reforms that can
      effectively address barriers to student learning and promote healthy development.
      Continuing education is seen as key to enabling school nurses to build capacity
      for such roles and functions. The newly formed Center for Mental Health in
      Schools at the University of California, Los Angeles (UCLA) hopes to be of
      assistance in this respect. This presentation highlights the Center's orientation
      to mental health in schools and offers a draft outline for related continuing
      education.

PMID- 9283379
TI  - Newman's theory and insulin dependent diabetes mellitus in adolescence.
AB  - Application of Margaret Newman's theory of Health as Expanding Consciousness is
      presented as beneficial for both the school nurse and the adolescent with Insulin
      Dependent Diabetes Mellitus (IDDM). The tenets of Newman's theory are reviewed
      and application drawn to adolescent development, the management of IDDM, and the
      development of an Individualized Healthcare Plan (IHP). Implications of the
      theory for school nurse case management and the process of identifying an
      adolescent's meaning of health are explored.

PMID- 9283378
TI  - Children's perceptions concerning school injuries.
AB  - This prospective study examined characteristics of school-related injuries in
      grades K-6 and children's perceptions regarding prevention and environmental
      influences. Injuries were most likely to occur on the playground, were most
      frequent for first and second graders, and for boys. Only 30% of the sample
      perceived that they could have prevented their injury. This perception was more
      frequent for children in higher grades. Fifty percent perceived an environmental
      influence. The Health Promotion Model was used as the theoretical framework to
      guide this investigation and provide implications for practice. School nurses are
      in an ideal position to counsel children on taking responsibility for their
      safety through preventive thinking.

PMID- 9283380
TI  - Preventing verbal harassment and violence toward gay and lesbian students.
AB  - School nurses (as well as other school personnel) have a role and a
      responsibility to help prevent verbal harassment and violence toward gay and
      lesbian students. The literature about verbal harassment and violence toward
      students in schools is scant, and there is even less written about the school
      nurse's role in addressing such concerns. This article points out the potential
      role of school nurses in addressing this issue if they will put aside personal
      biases and get involved in, or initiate, homophobia awareness programs and
      advocate for gay and lesbian students.

PMID- 9283381
TI  - Adaptation: a concept analysis.
AB  - The concept of adaptation is historically evident in nursing practice. Florence
      Nightingale showed how the environment required adaptation to meet the needs of
      the patient. Following her lead, several nurse theorists developed models with
      examples of the concept of adaptation: the nurse either adapts to the patient's
      needs, works to help the patient adapt to the environment, or adapts the
      environment to the needs of the patient. Sr. Callista Roy's Adaptation Model of
      Nursing is one such nursing model. Although this model has been applied in many
      clinical and administrative areas, the use of the concept in a school setting
      with special-need's student requires additional definition and clarification. The
      goal of this concept analysis paper is to clarify and explore the definition of
      adaptation in the school setting with application to an Individualized Healthcare
      Plan (IHP).

PMID- 9283382
TI  - Rapunzel's place.
AB  - This paper describes an innovative approach to personal hygiene education and
      intervention and pediculosis management in an elementary school. The three-phase
      project consisted of a hand-washing program, distribution of personal hygiene
      packets, pediculosis education, and intervention which culminated in the
      establishment of a school-based beauty salon.

PMID- 9283383
TI  - Role strain and role ambiguity revisited.

PMID- 9283384
TI  - A personal perspective: returning to a RN completion program.

PMID- 9283385
TI  - Appropriate nursing care for the pregnant male.

PMID- 9283386
TI  - Native American teens in Project Takoja.

PMID- 9283387
TI  - The current story line on terminal illness.

PMID- 9283388
TI  - Health's missing millions.

PMID- 9283389
TI  - Setting the record straight.

PMID- 9283391
TI  - Teenage hotline.

PMID- 9283392
TI  - Keeping bullies at bay.

PMID- 9283393
TI  - Short cuts.

PMID- 9283394
TI  - A largely hidden problem.

PMID- 9283395
TI  - A vision of community care.

PMID- 9283396
TI  - From reflection to reality.

PMID- 9283397
TI  - Community-led services for mental health care: a study.
AB  - This paper reports findings from a study into the effects of relocating untrained
      personnel from the hospital into the community, over a nine-month period. The
      study measured the dependent variables of hospital admissions, length of stay,
      resultant cost savings and community caseloads. Non-significant decreases
      occurred in bed occupancy as well as increases in bed occupancy, more demanding
      community psychiatric nurse (CPN) caseloads and an increasing use of the
      community services by females. Future studies will need to distinguish the most
      appropriate models of service delivery in a community setting. The findings,
      verified nationally, have major ramifications for mental health nurses if they
      are to provide effective care to the seriously mentally ill patient.

PMID- 9283398
TI  - Literature searching for systematic reviews.

PMID- 9283399
TI  - Care of patients undergoing immunoglobulin therapy.
AB  - Immunoglobulin infusion is becoming more widely used as treatment for a variety
      of conditions. This article describes the background and uses of immunoglobulin
      therapy and the nursing care of patients undergoing this treatment.

PMID- 9283400
TI  - Venepuncture.

PMID- 9283401
TI  - Community nurses as purchasers of secondary services for their patients and
      clients.

PMID- 9283402
TI  - Ominous silence on pay.

PMID- 9283403
TI  - Community care choice means radical change.

PMID- 9283404
TI  - Moving the board.

PMID- 9283405
TI  - Mersey killing.

PMID- 9283406
TI  - When bias blinds.

PMID- 9283407
TI  - Ovacoming cancer.

PMID- 9283408
TI  - Any old iron.

PMID- 9283409
TI  - Jobs for the faithful.

PMID- 9283410
TI  - A platform for planning.

PMID- 9283411
TI  - Oil protection.

PMID- 9283412
TI  - Nose relief.

PMID- 9283413
TI  - Setting up and developing clinical supervision.

PMID- 9283414
TI  - Defining the role of assessors, mentors and supervisors: Part 1.
AB  - This study, carried out over a period of four years, aimed to establish what
      happens in nursing practice in relation to assessing clinical competence of
      nursing students during their Common Foundation Programme (CFP). The study was
      based upon the experiences and perceptions of 155 skilled practitioners and 300
      students. Many themes and categories emerged, including role overlap and the lack
      of understanding of the role of the practitioner who is responsible for assessing
      student performance on practice placement during the CFP. This week we look at
      the data relating to the 155 skilled practitioners and next week we will review
      the student data and final data from the assessors, and make some recommendations
      for practice.

PMID- 9283415
TI  - The discharge process for palliative care patients.
AB  - This article describes the response of staff at a specialist palliative care
      service to the need for effective discharge planning. Hospice and community
      nurses were invited to give their views on the discharge of palliative care
      patients. The authors discuss the strategy for change and how it was implemented
      and evaluated.

PMID- 9283417
TI  - Central venous lines.

PMID- 9283416
TI  - Evaluating an osteoporosis service using a focus group.
AB  - Evaluation of any service should determine whether the service meets patients'
      perceived needs as well as their identified medical needs. This article describes
      the use of a focus group to evaluate a service for women with a diagnosis of
      osteoporosis.

PMID- 9283418
TI  - The candidates who are standing in the UK Central Council elections.

PMID- 9283419
TI  - Nursing's big challenge.

PMID- 9283421
TI  - The future of nurse education.

PMID- 9283422
TI  - Beds not bombs.

PMID- 9283420
TI  - Assistance or abuse?

PMID- 9283423
TI  - People not paper.

PMID- 9283424
TI  - Queue busters.

PMID- 9283425
TI  - Under the spotlight.

PMID- 9283426
TI  - Supportive models.

PMID- 9283427
TI  - Emergency IT.

PMID- 9283428
TI  - Nerve stimulation for low back pain--a review.

PMID- 9283429
TI  - Defining the role of assessors, mentors and supervisors: Part 2.
AB  - This is the second part of a study, carried out over four years, which examined
      what happens in nursing practice in relation to assessing the clinical competence
      of nursing students during their Common Foundation Programme (CFP). The study was
      based upon the experiences and perceptions of 155 skilled practitioners and 300
      students. Many themes and categories emerged, including role overlap and lack of
      understanding of the role of the practitioner who has been charged with the
      responsibility of assessing student performance on practice placement during the
      CFP. Last week we reported the data on the skilled practitioners, and this week
      we look at the student and assessor data at the end of the project. Most students
      accepted the dual role and, at times, even the triple role of assessor, mentor
      and/or supervisor forced upon practitioners, provided that the practitioners
      assessing them were well prepared and 'trained' as assessors.

PMID- 9283431
TI  - Wedding rings and hospital-acquired infection.
AB  - Some theatre nurses are reluctant to remove their wedding rings when scrubbing
      up. This article reviews the literature and concludes that keeping rings on may
      put the patient at risk of nosocomial (hospital-acquired) infection.

PMID- 9283430
TI  - Management of systemic lupus erythematosus: Part 1.
AB  - This is the first of two articles examining the management of systemic lupus
      erythematosus. This week's article explores the history, aetiology, symptoms and
      treatment of the disease and next week, the importance of patient education
      programmes is described.

PMID- 9283432
TI  - Leg ulcer assessment by Doppler ultrasound.

PMID- 9283434
TI  - Ending of student grants outrages nursing unions.

PMID- 9283433
TI  - Did Dearing not realise that nursing is now the largest student body in some
      universities?

PMID- 9283435
TI  - Sent from heaven.

PMID- 9283436
TI  - A perfect partnership in practice.

PMID- 9283438
TI  - Swansong for free degrees.

PMID- 9283437
TI  - What is the doctrine of double effect?

PMID- 9283440
TI  - 20 questions.

PMID- 9283441
TI  - Smells like mean spirit.

PMID- 9283439
TI  - First few weeks as a member of parliament.

PMID- 9283443
TI  - In search of perfection.

PMID- 9283442
TI  - Unhappy eater.

PMID- 9283444
TI  - The missing links.

PMID- 9283446
TI  - Due south.

PMID- 9283445
TI  - In it together.

PMID- 9283447
TI  - Times gone by.

PMID- 9283448
TI  - Crying together, laughing together.

PMID- 9283449
TI  - If physiotherapists want to mobilise patients they should do so without expecting
      nurses to carry their burden.

PMID- 9283450
TI  - Using airway pressure.
AB  - This is the third part in the series Care is Critical which looks at the more
      complex technological interventions nurses may now have to deal with on general
      wards or in the community. This article looks at continuous positive airway
      pressure, an oxygen delivery system which can relieve significant respiratory
      distress in some cases. The first two were published on June 25.

PMID- 9283451
TI  - Patient roles in decision-making.
AB  - Participation by patients in making decisions about treatment is widely
      encouraged. However, there is little evidence from patients about their
      preferences with respect to this. This study used a card-sort approach to explore
      the actual and preferred participation in making decisions about treatment among
      a sample of 405 patients with renal disease. The study identified that the
      majority preferred to adopt a passive role in decision-making. The findings
      highlight the need for nurses to identify individual patient preferences with
      respect to participation and to explore why a person may choose to adopt a
      particular decision-making role.

PMID- 9283452
TI  - Palliative care and learning disabilities.
AB  - This article explores the problems nurses may come across when a client with a
      learning disability develops a terminal illness. The client's understanding of
      illness and death is discussed. Also explored is the client's need for
      relationships, as well as the family's needs. Close cooperation between carers
      and all professionals involved is essential for providing maximum and appropriate
      support.

PMID- 9283453
TI  - People choose nursing for love, not money.
AB  - This study looks at the occupational values of nursing students in the mid-1990s
      and compares the findings with a similar survey carried out in 1980 and published
      in Nursing Times. Both sets of respondents were particularly motivated by working
      with, and helping people. Extrinsic motivators, such as earning good money and
      having status and prestige, were not rated so highly.

PMID- 9283454
TI  - Who cares for skin?

PMID- 9283455
TI  - Health surveillance: preventing occupational asthma.

PMID- 9283457
TI  - Dermatological engineering.

PMID- 9283456
TI  - Osteopathy: improving the status of alternative healthcare.

PMID- 9283458
TI  - Aerobic fitness testing: an update.
AB  - This study confirms that all three tests are reliable tools for the assessment of
      cardiorespiratory fitness and the prediction of aerobic capacity. While this
      particular study consisted of active, youthful subjects, subsequent studies at
      University College Chester have found similar findings with larger databases and
      a wider cross-section of subjects. The Astrand cycle test and Chester step test
      are submaximal tests with error margins of 5-15 per cent and therefore, not as
      precise as maximal testing. However, they still give a reasonably accurate
      reflection of an individual's fitness without the cost, time, effort and risk on
      the part of the subject. The bleep test is a low-cost maximal test designed for
      well-motivated, active individuals who are used to running to physical
      exhaustion. Used on other groups, results will not accurately reflect
      cardiorespiratory fitness values. While all three tests have inherent advantages
      and disadvantages, perhaps the most important factors are the knowledge and
      skills of the tester. Without a sound understanding of the physiological
      principles underlying these tests, and the ability to conduct an accurate
      assessment and evaluation of results in a knowledgeable and meaningful way, then
      the credibility of the tests and the results become suspect. However, used
      correctly, aerobic capacity tests can provide valuable baseline data about the
      fitness levels of individuals and data from which exercise programmes may be
      developed. The tests also enable fitness improvements to be monitored, help to
      motivate participants by establishing reasonable and achievable goals, assist in
      risk stratification and facilitate participants' education about the importance
      of physical fitness for work and for life. Since this study was completed,
      further tests have been repeated on 140 subjects of a wider age and ability
      range. This large database confirms the results found in this study.

PMID- 9283459
TI  - Stress management: the five-year plan.

PMID- 9283461
TI  - Heaven-made marriage.

PMID- 9283460
TI  - Occupational health nursing in Germany.

PMID- 9283462
TI  - Personnel managers polled on company drug abuse.

PMID- 9283463
TI  - A multicentre health promotion programme for coronary heart disease.

PMID- 9283464
TI  - Community health education: future skills or a dead-end?
AB  - The introduction of Community PREP was welcomed as a chance for OHNs to become
      part of the community health team. However, recent plans for primary health have
      excluded OH nursing, and the disappearance of diploma level education has raised
      concerns that OHNs are not being provided with the core skills required by
      employers. HELEN KOGAN asks if OHNs are not to be included within the primary
      healthcare team, where do they fit? And if not, are the right skills for
      employment being provided by degree-level education?

PMID- 9283465
TI  - Healthy feet for a productive workforce.

PMID- 9283466
TI  - The road to occupational health in a developing country.

PMID- 9283468
TI  - Dermatitis elicits industry-wide concern.

PMID- 9283467
TI  - The start of a new era for health and safety?

PMID- 9283470
TI  - Alcohol abuse: the hidden diagnosis.

PMID- 9283469
TI  - Sick building syndrome: a suitable case for treatment.

PMID- 9283471
TI  - Drugs and alcohol in the workplace.

PMID- 9283472
TI  - Occupational health and the houseworker.

PMID- 9283473
TI  - Manual handling training and changes in work practices.

PMID- 9283474
TI  - The rationale behind workplace health promotion.

PMID- 9283475
TI  - Audit--and breathe easier.

PMID- 9283476
TI  - Pre-employment medicals and the duty of care.

PMID- 9283477
TI  - Latex glove allergy.

PMID- 9283478
TI  - The Disability Discrimination Act 1995--an OHP challenge.

PMID- 9283479
TI  - Graham Johnson steps down as SOHN chairman.

PMID- 9283481
TI  - Legal aspects of teleworking.

PMID- 9283480
TI  - Health and safety for teleworkers.

PMID- 9283482
TI  - Management skills--going alone.
AB  - Although the most important occasion for the use of the above techniques is early
      on in the call, remember that each time you want to change direction or change
      topic you have to 'gain attention' all over again. In the next article we will
      look at some other selling issues, namely, questioning and listening skills,
      features and benefits, behavioural selling and keeping the 'back door' closed. In
      the meantime, if you have any questions about selling, or a management issue,
      then feel free to contact me through OH magazine-anonymously if you prefer-and I
      will be pleased to answer your questions.

PMID- 9283483
TI  - A case for stress counselling.

PMID- 9283484
TI  - National skin care survey highlights training shortcomings.

PMID- 9283486
TI  - Preventive health screening in Greece.

PMID- 9283487
TI  - [Nursing in Venezuela: an impossible profession].

PMID- 9283485
TI  - EU health and safety. A vision for the future.

PMID- 9283488
TI  - [The bet].

PMID- 9283489
TI  - [Esophageal atresia: caring for the child and its family].

PMID- 9283492
TI  - [The medical contex of hunger strikes].

PMID- 9283490
TI  - [When the child presents...].

PMID- 9283491
TI  - [Assistance to hunger strikers: a current problem].

PMID- 9283494
TI  - [Directives for medical and nursing assistance].

PMID- 9283493
TI  - [Help for hunger strikers].

PMID- 9283495
TI  - [Hunger strike: a legal approach].

PMID- 9283496
TI  - ["Stimulation" at home; it is possible].

PMID- 9283497
TI  - [Palliative care of urinary incontinence].

PMID- 9283498
TI  - [Sterilize your endoscopes carefully].

PMID- 9283500
TI  - [Education by couples and prevention of AIDS].

PMID- 9283499
TI  - [Zona and herpes: current viral diseases].

PMID- 9283501
TI  - [Can one learn to breathe?].

PMID- 9283503
TI  - Impaired color vision in cocaine-withdrawn patients.
AB  - BACKGROUND: The main reinforcing effect of cocaine happens by altering
      dopaminergic neurotransmission in the brain reward systems. Dopamine is found in
      high concentrations in the retina in which it plays an important role in color
      vision. Therefore, we investigated whether cocaine-dependent patients might have
      impaired color vision. METHODS: We compared patients recently withdrawn from
      cocaine (n = 31) with matched normal controls (n = 31) on 2 color vision tests.
      RESULTS: Cocaine-withdrawn patients had significantly higher error scores than
      matched controls on the Farnsworth-Munsell 100-hue and Lanthony desaturated D-15
      color vision tests. Also, 23 of the 31 cocaine-withdrawn patients had blue-yellow
      color vision losses on the Farnsworth-Munsell 100-hue test compared with 3
      controls (P < .001, chi 2 test) and 15 had blue-yellow color vision loss on the
      Lanthony desaturated D-15 test compared with 2 controls (P < .001, chi 2 test).
      CONCLUSIONS: These significantly higher test error scores and blue-yellow color
      vision losses suggest that color vision is impaired in cocaine-withdrawn
      patients. Color vision testing may be useful in future studies of cocaine
      dependent patients.

PMID- 9283502
TI  - Drug abuse and addiction treatment research. The next generation.

PMID- 9283504
TI  - Fluoxetine in depressed alcoholics. A double-blind, placebo-controlled trial.
AB  - BACKGROUND: The selective serotonergic medication fluoxetine has demonstrated
      efficacy in the treatment of major depression and has suggested efficacy in the
      treatment of alcoholism. However, no completed trials with any selective
      serotonergic medication have been reported in patients who display both major
      depression and alcoholism, despite previous observations that both depression and
      alcoholism are associated with low serotonergic functioning. METHODS: Fifty-one
      patients diagnosed as having comorbid major depressive disorder and alcohol
      dependence were randomized to receive fluoxetine (n = 25) or placebo (n = 26) in
      a 12-week, double-blind, parallel-group trial. Weekly ratings of depression and
      alcohol consumption were obtained throughout the 12-week course of the study.
      RESULTS: The improvement in depressive symptoms during the medication trial was
      significantly greater in the fluoxetine group than in the placebo group. Total
      alcohol consumption during the trial was significantly lower in the fluoxetine
      group than in the placebo group. CONCLUSIONS: Fluoxetine is effective in reducing
      the depressive symptoms and the alcohol consumption of patients with comorbid
      major depressive disorder and alcohol dependence. It is unknown whether these
      results generalize to the treatment of less depressed and less suicidal
      alcoholics.

PMID- 9283505
TI  - Prediction of compliance with outpatient referral in patients with schizophrenia
      and psychoactive substance use disorders.
AB  - BACKGROUND: Most patients with concurrent schizophrenia and psychoactive
      substance use disorders may be adequately treated as outpatients. However, many
      do not comply with outpatient referrals and are therefore at heightened risk for
      rehospitalization. METHOD: Drawing on standardized interview data collected
      during an index hospitalization, we developed a logistic regression model to
      predict compliance with outpatient treatment. The model was tested on a
      confirmatory sample, and its sensitivity and specificity were further evaluated
      in a cross-validation study of 1000 random samples. RESULTS: In a reference
      sample, the logistic function distinguished compliant from noncompliant patients
      in 37 (76%) of 49 cases. In a confirmatory sample, compliance status was
      predicted for 11 (78%) of 14 patients with a sensitivity of 1.00 and a
      specificity of 0.67. Women and patients with negative syndrome schizophrenia were
      compliant with outpatient referral, whereas those with mixed syndromes were most
      likely to be noncompliant. Cross-validation supports the stability of the model.
      CONCLUSION: While most persons with schizophrenia and concurrent substance abuse
      comply with integrated outpatient treatment, most who cannot may be predicted in
      advance.

PMID- 9283506
TI  - Buprenorphine vs methadone maintenance treatment for concurrent opioid dependence
      and cocaine abuse.
AB  - BACKGROUND: Buprenorphine, a partial mu-agonist and kappa-antagonist, has been
      proposed as an alternative to methadone for maintenance treatment of opioid
      dependence, especially for patients with concurrent cocaine dependence or abuse.
      This study evaluated whether higher maintenance doses of buprenorphine and
      methadone are superior to lower doses for reducing illicit opioid use and whether
      buprenorphine is superior to methadone for reducing cocaine use. METHODS: A total
      of 116 subjects were randomly assigned to 1 of 4 maintenance treatment groups
      involving higher or lower daily doses of sublingual buprenorphine (12 or 4 mg) or
      methadone (65 or 20 mg) in a double-blind, 24-week clinical trial. Outcome
      measures included retention in treatment and illicit opioid and cocaine use as
      determined by urine toxicology testing and self-report. RESULTS: There were
      significant effects of maintenance treatment on rates of illicit opioid use, but
      no significant differences in treatment retention or the rates of cocaine use.
      The rates of opioid-positive toxicology tests were lowest for treatment with 65
      mg of methadone (45%), followed by 12 mg of buprenorphine (58%), 20 mg of
      methadone (72%), and 4 mg of buprenorphine (77%), with significant contrasts
      found between 65 mg of methadone and both lower-dose treatments and between 12 mg
      of buprenorphine and both lower-dose treatments. CONCLUSIONS: The results support
      the superiority of higher daily buprenorphine and methadone maintenance doses vs
      lower doses for reducing illicit opioid use, but the results do not support the
      superiority of buprenorphine compared with methadone for reducing cocaine use.

PMID- 9283507
TI  - The National Institute on Drug Abuse Collaborative Cocaine Treatment Study.
      Rationale and methods.
AB  - The National Institute on Drug Abuse Collaborative Cocaine Treatment Study is a
      large, multisite psychotherapy clinical trial for outpatients who meet the DSM-IV
      criteria for cocaine dependence. For 480 randomized patients, the outcomes of 4
      treatments are compared for an 18-month period. All treatments include group drug
      counseling. One treatment also adds cognitive therapy, one adds supportive
      expressive psychodynamic therapy, and one adds individual drug counseling; one
      consists of group drug counseling alone. In addition, 2 specific interaction
      hypotheses, one involving psychiatric severity and the other involving degree of
      antisocial personality characteristics, are being tested. This article describes
      the main aims of the project, the background and rationale for the study design,
      the rationale for the choice of treatments and patient population, and a brief
      description of the research plan.

PMID- 9283508
TI  - Problem-service 'matching' in addiction treatment. A prospective study in 4
      programs.
AB  - BACKGROUND: Our initial attempts to "match" substance-abuse patients from an
      employee assistance program to an optimal setting or program failed.
      Scientifically, we found no differential predictors of better outcomes by setting
      or program. From a practical perspective, it was impossible to place patients in
      the intended programs. This led to a second study, designed to identify specific
      patient problems and match professional services to those problems within each of
      the 4 programs. METHODS: Ninety-four new patients admitted to 4 substance-abuse
      treatment programs were randomly assigned to standard treatment and treated in
      the usual manner or were assigned to "matched" services, in which patients
      received at least 3 professional sessions directed at their important employment,
      family, or psychiatric problems. RESULTS: Matched patients stayed in treatment
      longer, were more likely to complete treatment, and had better posttreatment
      outcomes than did the standard patients treated in the same programs.
      CONCLUSIONS: For logistical, financial, and clinical reasons, it is improbable
      that patients will be matched to specific types of programs. However, within any
      program, it is possible and practical to match appropriate services to patients'
      specific treatment problems. This strategy was clinically and administratively
      practical, attractive to patients, and responsible for a 20% to 30% increase in
      the effectiveness of this substance-abuse treatment system.

PMID- 9283509
TI  - Naltrexone and alcohol dependence. Role of subject compliance.
AB  - BACKGROUND: Two previous double-blind, placebo-controlled studies demonstrated
      that naltrexone (50 mg/d) reduces alcohol drinking in alcohol-dependent subjects.
      In both studies, treatment compliance was excellent. However, a robust treatment
      effect size for naltrexone relative to placebo has been shown for compliant
      subjects but not for subjects who missed research visits. The goal of this study
      was to determine the effectiveness of naltrexone in subjects who received
      psychosocial treatment in a more naturalistic setting with respect to the role of
      treatment attendance and medication compliance. METHODS: Ninety-seven alcohol
      dependent subjects were randomly assigned to receive either naltrexone (n = 48)
      or matching placebo (n = 49) for 12 weeks. All subjects received individual
      counseling (twice per week for the first month followed by once per week).
      RESULTS: Overall, naltrexone showed only modest effects in reducing alcohol
      drinking for the 12 weeks of treatment. However, naltrexone treatment efficacy
      improved across a variety of outcome measures for subjects who completed
      treatment and were highly compliant with taking medication. CONCLUSIONS:
      Naltrexone is clinically effective relative to placebo in individuals who comply
      with the treatment protocol and take medication. The modest treatment effects in
      the entire sample suggest that the clinical efficacy of naltrexone could be
      improved by enhancing treatment compliance.

PMID- 9283510
TI  - Double-blindness procedures, rater blindness, and ratings of outcome.
      Observations from a controlled trial.
AB  - BACKGROUND: We determined whether blindness in a double-blind randomized
      controlled trial of alprazolam and exposure therapies in patients with panic
      disorder and agoraphobia was maintained in assessors and patients, what were the
      factors related to "unblinding," and whether unblinding was associated with
      clinical outcome. METHOD: In 129 patients with panic disorder and agoraphobia who
      were randomized to alprazolam-exposure, placebo-exposure, alprazolam-relaxation,
      or placebo-relaxation conditions, blindness was tested at the end of treatment by
      the independent assessors' and patients' classification of the treatment
      condition. RESULTS: Assessors' classifications were correct in 82% of the
      alprazolam group and 78% of the placebo group; corresponding figures for
      patients' classifications were 73% and 70%, respectively. Factors associated with
      unblinding included drug side effects but not assessors' ratings of treatment
      outcome. CONCLUSION: Judgment of the validity of the outcome of a randomized
      controlled trial is easier if the report notes not only the use of a double
      blindness procedure but also details how blind the raters remained and how any
      unblinding affected their ratings of clinical outcome.

PMID- 9283511
TI  - Noradrenergic and serotonergic function in posttraumatic stress disorder.
AB  - BACKGROUND: Yohimbine hydrochloride produces marked behavioral and cardiovascular
      effects in combat veterans with posttraumatic stress disorder (PTSD). In the
      present study, yohimbine was used as a probe of noradrenergic activity, and meta
      chlorophenylpiperazine (m-CPP) as a probe of serotonergic activity. To our
      knowledge, this is the first study to describe the behavioral and cardiovascular
      effects of meta-CPP in patients with PTSD, and to compare these effects with
      those of yohimbine. METHOD: Twenty-six patients with PTSD and 14 healthy subjects
      each received an intravenous infusion of yohimbine hydrochloride (0.4 mg/kg), m
      CPP (1.0 mg/kg), or saline solution on 3 separate test days in a randomized
      balanced order and in double-blind fashion. Behavioral and cardiovascular
      measurements were determined at multiple times. RESULTS: Eleven (42%) of the
      patients with PTSD experienced yohimbine-induced panic attacks and had
      significantly greater increases compared with controls in anxiety, panic, and
      PTSD symptoms, but not in cardiovascular measurements. Eight patients (31%) with
      PTSD experienced m-CPP-induced panic attacks and had significantly greater
      increases compared with controls in anxiety, panic, and PTSD symptoms, and in
      standing diastolic blood pressure. Yohimbine-induced panic attacks tended to
      occur in different patients from m-CPP-induced panic attacks. CONCLUSION: These
      data suggest the presence of 2 neurobiological subgroups of patients with PTSD,
      one with a sensitized noradrenergic system, and the other with a sensitized
      serotonergic system.

PMID- 9283512
TI  - Clozapine withdrawal: serotonergic or dopaminergic mechanisms?

PMID- 9283513
TI  - Anterior paralimbic mediation of procaine-induced emotional and psychosensory
      experiences.

PMID- 9283514
TI  - Methodology, feasibility, safety and diagnostic accuracy of dobutamine stress
      echocardiography.
AB  - Large numbers of patients referred for evaluation of chest pain are unable to
      perform adequate, diagnostic exercise testing. In these patients, dobutamine
      stress echocardiography (DSE) represents an alternative, exercise-independent
      stress modality. Apart from the approximately 5% of patients with an inadequate
      acoustic window, 10% of patients referred for this test have nondiagnostic
      (submaximal negative) test results. Serious side effects during or shortly after
      DSE are uncommon, with ventricular fibrillation or myocardial infarction
      occurring in approximately 1 of 2,000 studies. No deaths have been reported. On
      the basis of a total number of 2,246 patients, reported in 28 studies, the
      sensitivity, specificity and accuracy of the test for the detection of coronary
      artery disease (CAD) were 80%, 84% and 81%, respectively. Mean sensitivities for
      one-, two- and three-vessel disease were 74%, 86% and 92%, respectively. The
      sensitivity for detection of disease in the left circumflex coronary artery (55%)
      was lower, both compared with that for left anterior descending (72%) and right
      coronary artery disease (76%). The sensitivity of predicting multivessel disease
      by multiregion echocardiographic abnormalities varied widely, from 8% to 71%. In
      direct comparisons, DSE was superior to exercise electrocardiography and
      dipyridamole echocardiography and comparable to exercise echocardiography and
      radionuclide imaging. DSE is a useful, feasible and safe exercise-independent
      stress modality for assessing the presence, localization and extent of CAD.

PMID- 9283516
TI  - From research to clinical practice: current role of intracoronary physiologically
      based decision making in the cardiac catheterization laboratory.
AB  - Decisions regarding coronary interventions should be combined with objective
      evidence of myocardial ischemia. The most common physiologic approach utilizes
      hospital facilities outside the catheterization laboratory, requiring additional
      time and cost. With the introduction of sensor-tipped angioplasty guide wires,
      distal coronary flow velocity and pressure can be obtained in the cardiac
      catheterization laboratory, facilitating physiologically based decisions
      regarding the need for intervention. In the catheterization laboratory,
      physiologically significant stenoses can be characterized as having impaired post
      stenotic coronary flow reserve < 2.0 and pressure-derived fractional flow reserve
      < 0.75, both variables related strongly to positive ischemic perfusion imaging or
      stress testing results. Deferring coronary interventions on the basis of normal
      translesional physiology is safe and is associated with a low rate (< 10%) of
      lesion progression over a 10-month follow-up period. Preliminary data indicate
      that excellent physiologic and anatomic end points after balloon angioplasty are
      associated with low (< 20%) restenosis rates at 6-month follow-up. Clinically
      relevant relations of in-laboratory physiology support the insight that
      physiologic, as much as or more than anatomic variables, ultimately determine the
      functional status of a patient. Current data suggest that an intracoronary
      physiologic approach complements coronary lumenology and appears to have
      important clinical and economic implications for patients undergoing invasive
      evaluation and treatment of coronary artery disease.

PMID- 9283515
TI  - Improvement in inducible ischemia during dobutamine stress echocardiography after
      transmyocardial laser revascularization in patients with refractory angina
      pectoris.
AB  - OBJECTIVES: The purpose of this ongoing study is to determine whether
      transmyocardial laser revascularization (TMLR) can lessen inducible ischemia and
      improve contractile reserve in patients with refractory angina pectoris.
      BACKGROUND: TMLR is an emerging surgical technique for the treatment of
      myocardial ischemia and angina pectoris not amenable to conventional percutaneous
      or surgical revascularization. Objective data documentating a reduction in
      ischemia during noninvasive stress testing after TMLR are rare. METHODS: Fifteen
      patients with severe coronary artery disease unsuitable for treatment with
      standard revascularization techniques were studied with dobutamine stress
      echocardiography (DSE) before TMLR. Of the 12 patients who underwent TMLR, DSE
      was repeated at 3 months postoperatively in 11 patients and at 6 months in 9
      patients. Stress echocardiograms were analyzed for inducible ischemia, with
      calculation of the wall motion score index (WMSI). Heart rate and dobutamine dose
      achieved at peak stress were also assessed as indexes of stress tolerance.
      RESULTS: Compared with that before TMLR, wall motion at rest for all myocardial
      segments did not change significantly after TMLR, although there was a mild
      improvement in the WMSI of the lased myocardial regions ([mean +/- SD] 1.64 +/-
      0.34 after vs. 1.78 +/- 0.34 before TMLR, p < 0.05). Overall WMSI at peak stress
      improved markedly after TMLR (1.70 +/- 0.30 after vs. 2.06 +/- 0.31 before TMLR,
      p < 0.002), with the improvement in WMSI limited to the lased segments only (1.47
      +/- 0.31 after vs. 2.15 +/- 0.34 before TMLR, p < 0.0004). The improvement in
      WMSI with stress resulted primarily from a decrease in the percentage of ischemic
      segments (47% before vs. 23% after TMLR, p < 0.0008), with no change in the
      percentage of infarcted segments (23% before vs. 26% after TMLR). Heart rate (83
      +/- 5 beats/min before vs. 102 +/- 21 beats/min after TMLR, p = 0.01) and
      dobutamine infusion rate (26 +/- 9 micrograms/kg body weight per min before vs.
      34 +/- 9 micrograms/kg per min after TMLR) achieved at peak stress also increased
      postoperatively, consistent with improved stress tolerance. The reduction in
      ischemic wall motion abnormalities and improved stress tolerance persisted at 6
      months, without evidence of further improvement or deterioration of function over
      time. CONCLUSIONS: TMLR performed in patients with refractory angina pectoris
      reduces ischemic wall motion abnormalities and improves stress-induced tolerance
      during dobutamine echocardiography. These beneficial effects persist up to 6
      months postoperatively.

PMID- 9283517
TI  - Significance of persistent left ventricular dysfunction during recovery after
      dobutamine stress echocardiography.
AB  - OBJECTIVES: This study sought to determine the duration of new or worsening left
      ventricular regional wall motion abnormalities (RWMAs) after dobutamine stress
      echocardiography (DSE) and their relation to the extent of coronary artery
      disease (CAD). BACKGROUND: Despite extensive reports on DSE, little is known
      about the duration of new or worsening RWMAs during recovery. We hypothesized
      that the persistence of RWMAs during recovery may be associated with the extent
      of CAD and therefore ischemia. METHODS: Sixty-five consecutive patients with
      positive results on DSE and angiographically documented CAD were studied. Each
      patient underwent 12-lead electrocardiography and two-dimensional
      echocardiography at rest, during dobutamine infusion and continuously during
      recovery to assess the recovery time of ischemic myocardial regions. RESULTS: All
      patients had at least one ischemic region during DSE. Complete resolution of
      RWMAs occurred within 25 min in patients with multivessel CAD, within 20 min in
      those with two-vessel disease and within 15 min in those with single-vessel
      disease (p < 0.001). The greater the wall motion score index at peak stress, the
      longer the duration of RWMAs into the recovery phase (p < 0.01). RWMAs persisted
      long after normalization of each patient's symptoms, electrocardiographic (ECG)
      changes, heart rate and rate-pressure product during recovery. CONCLUSIONS: We
      demonstrated that normalization of left ventricular RWMAs occurs after resolution
      of symptoms and ECG changes during recovery. The time to recovery is related to
      the extent of CAD and myocardial ischemia as well as to the presence or absence
      of collateral circulation. These findings may represent stunned myocardium after
      brief period of ischemia.

PMID- 9283518
TI  - Dobutamine stress tele-echocardiography for evaluation of emergency department
      patients with chest pain.
AB  - OBJECTIVES: The practically and accuracy of dobutamine stress tele
      echocardiography (DSTE) were assessed in patients presenting to the emergency
      department with chest pain. BACKGROUND: Many patients evaluated for chest pain in
      the emergency department (ED) are admitted to the hospital needlessly because of
      the difficulty in differentiating noncardiac chest pain from myocardial ischemia.
      METHODS: One hundred sixty-three patients with no evidence of myocardial
      infarction on initial blood studies or the electrocardiogram who were recommended
      for hospital admission to rule out myocardial infarction or myocardial ischemia
      were enrolled in this four-phase study. Rest echocardiography was performed in
      the ED, and the images were transmitted to a cardiologist for interpretation. If
      the results were normal, DSTE was then administered by a trained nurse. In the
      first three phases, all patients were admitted for observation regardless of the
      results of DSTE. In the fourth phase, those having normal DSTE results were able
      to be released. RESULTS: The test was completed within an average of 5.4 h of
      presentation to the ED. The sensitivity and specificity of DSTE versus clinical
      and cardiac catheterization findings were 89.5% and 88.9%, respectively, with a
      negative predictive value for DSTE of 98.5%. Patients experienced frequent mild
      side effects (54.7%), but few (6.3%) caused the test to be discontinued
      prematurely. In phase 4 of the study, 72% of those slated for hospital admission
      because of cardiac risk factors and chest pain suggesting myocardial ischemia
      were discharged after normal DSTE results. CONCLUSIONS: The use of DSTE in the
      evaluation of patients presenting with chest pain may improve screening for those
      who can be safely released from the ED.

PMID- 9283519
TI  - Contractile reserve of dysfunctional myocardium after revascularization: a
      dobutamine stress echocardiography study.
AB  - OBJECTIVES: We sought to investigate the effects of revascularization on the
      contractile reserve of dysfunctional myocardium. BACKGROUND: The improvement in
      dysfunctional but viable myocardium after revascularization is frequently less
      than expected from the amount of contractile reserve detected on dobutamine
      stress echocardiography. The fate of the contractile reserve, when it does not
      result in an adequate contractile recovery, is unknown. METHODS: Basal
      contraction and contractile reserve of infarct zones were assessed by dobutamine
      stress echocardiography in 21 postinfarction male patients before and > 3 months
      after revascularization (30 infarct zones; mean +/- SD left ventricular ejection
      fraction 35 +/- 8%). An infarct zone wall motion score index (WMSI) was
      calculated. RESULTS: Before revascularization, contractile reserve was present in
      14 infarct zones (12 patients) and absent in 16 (9 patients). After
      revascularization, ejection fraction increased by 5 +/- 4% (p < 0.01) in patients
      classified as positive for contractile reserve and remained unchanged in those
      classified as negative. New York Heart Association classification improved in
      58.3% and 22.2% of patients, respectively. Basal contraction improved in eight
      zones with previous contractile reserve (57.1%) and in one zone without (6.3%) (p
      < 0.01). Contractile reserve was still evident in 13 zones with previous
      contractile reserve (93%; 8 with contractile recovery), and it developed in 6
      zones without (38%; none with contractile recovery). WMSI values after
      revascularization were decreased from values before revascularization during low
      dose dobutamine in zones with and without previous contractile reserve (p < 0.01
      and < 0.05, respectively). CONCLUSIONS: After revascularization, contractile
      reserve is maintained or even increases in viable infarct zones that do not
      recover as expected. It may also develop in some infarct zones judged not to be
      viable before revascularization. This increased contractile reserve may play a
      role in the functional improvement of patients after revascularization.

PMID- 9283521
TI  - Recanalization of chronic total coronary occlusions using a laser guide wire: a
      pilot study.
AB  - OBJECTIVES: This study sought to prospectively evaluate the performance of a
      laser guide wire in crossing chronic total coronary occlusions in patients with a
      failed previous mechanical guide wire attempt. BACKGROUND: Despite continued
      refinement of mechanical hardware available for coronary angioplasty, restoration
      and maintenance of blood flow through a chronically occluded coronary artery
      remains a true challenge. METHODS: Fifty patients with a chronic total coronary
      occlusion and a previous failed attempt at recanalization using mechanical guide
      wires were included. A mechanical attempt to cross the occlusion was repeated. In
      case of failure, an additional attempt was made with the laser guide wire.
      RESULTS: The median age of occlusion was 22 weeks (range 5 to 200), and the
      occlusion length was 23 +/- 11 mm (mean +/- SD). A repeat mechanical attempt was
      successful in six cases (12%). Dissection occurred in five other cases, and
      device crossover was not attempted. Thus, in 39 patients an attempt was made with
      the laser guide wire, with successful recanalization in 23 (59%). Thereby the
      overall success rate increased from 12% to 58% (29 of 50 patients). The amount of
      contrast medium used was 515 +/- 154 ml, fluoroscopy time was 99 +/- 43 min, and
      total procedure time was 2 h 48 min (+/- 55 min). Procedural success was achieved
      in 26 cases and clinical success (procedural success without in hospital events)
      in 24. In-hospital events were two non-Q wave myocardial infarctions related to
      subacute reocclusion. In one patient, a balloon dilation after laser guide wire
      perforation resulted in tamponade requiring pericardiocentesis. After a
      successful procedure, the angina class decreased from 2.9 +/- 0.2 to 1.4 +/- 0.7
      at 3 months of clinical follow-up. Six month angiographic follow-up was completed
      in all 24 eligible patients and showed vessel patency in 20 (80%). CONCLUSIONS:
      The use of the laser guide wire for recanalization of chronic total coronary
      occlusions refractory to treatment with mechanical guide wires is feasible and
      relatively safe and was successful in 59% of cases. This device must thus be
      considered a valuable addition to the interventional armamentarium and
      accordingly will be evaluated in a randomized clinical trial.

PMID- 9283520
TI  - Importance of estimated functional capacity as a predictor of all-cause mortality
      among patients referred for exercise thallium single-photon emission computed
      tomography: report of 3,400 patients from a single center.
AB  - OBJECTIVES: We sought to determine the relative influence of estimated functional
      capacity and thallium-201 (Tl-201) single-photon emission computed tomographic
      (SPECT) findings on prediction of short-term all-cause and cardiac-related
      mortality. BACKGROUND: Decreased functional capacity and abnormal Tl-201 SPECT
      findings are predictive of increased cardiovascular risk and mortality. However,
      the relative importance of these variables as predictors of all-cause mortality
      is not well established. METHODS: Analyses were based on 3,400 consecutive adults
      undergoing symptom-limited exercise Tl-201 SPECT testing at the Cleveland Clinic
      Foundation between September 1990 and December 1993; none had previous invasive
      procedures, heart failure or valve disease. Estimated functional capacity,
      classified by age and gender, and thallium perfusion defects, expressed as a
      stress extent thallium score on a 12-segment scale, were analyzed to determine
      their relative prognostic importance during 2 years of follow-up. RESULTS: Of
      3,400 patients, 108 (3.2%) died during follow-up; 32 deaths were identified as
      cardiac related. On univariable analysis, estimated functional capacity was a
      strong predictor of death, with 62 (57%) deaths occurring in patients achieving <
      6 metabolic equivalents (METs) (log-rank chi-square 86, p < 0.0001). On
      multivariable analysis, the strongest independent predictors of all-cause
      mortality were fair or poor functional capacity (adjusted relative risk [RR]
      3.96, 95% confidence interval [CI] 2.36 to 6.64, chi-square 27, p < 0.0001) and
      age (adjusted RR for 10 years 2.25, 95% CI 1.80 to 2.80, chi-square 27, p <
      0.0001). The presence of SPECT thallium perfusion defects was a less powerful
      predictor of death (for each two additional segments with defects, adjusted RR
      1.21, 95% CI 1.03 to 1.43, chi-square 5, p = 0.02). Cardiac mortality was
      predicted by both fair or poor functional capacity (adjusted RR 4.37, 95% CI 1.59
      to 12.00, chi-square 8, p = 0.004) and by stress extent thallium score (adjusted
      RR 1.62, 95% CI 1.25 to 2.11, chi-square 13, p = 0.0003). CONCLUSIONS: In this
      clinically low risk group, estimated functional capacity was a strong and
      overwhelmingly important independent predictor of all-cause mortality among
      patients undergoing exercise Tl-201 SPECT testing. The extent of myocardial
      perfusion defects was of comparable importance for the prediction of cardiac
      mortality.

PMID- 9283522
TI  - Transluminal extraction catheter atherectomy followed by immediate stenting in
      treatment of saphenous vein grafts.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effectiveness of
      transluminal extraction catheter (TEC) atherectomy followed by immediate Palmaz
      Schatz coronary stenting of coronary bypass vein grafts. BACKGROUND: Degeneration
      of saphenous vein coronary bypass grafts has become a common problem. Repeat
      bypass surgery is associated with greater risk and a poorer outcome than the
      initial operation. Moreover, percutaneous interventional procedures in vein
      grafts have been associated with high procedural complication rates, including
      distal embolization, and high restenosis rates. TEC atherectomy may reduce distal
      embolization, and stenting may reduce restenosis rates. METHODS: We evaluated the
      procedural, hospital and clinical outcomes of TEC atherectomy followed by
      immediate Palmaz-Schatz coronary stenting of 53 vein grafts in 49 consecutive
      patients. The strategy was to limit instrumentation to extraction debulking and
      to stabilizing the site with stent deployment before using balloon dilation for
      optimal gain in lumen diameter. RESULTS: Results are shown as mean value (95%
      confidence interval [CI]). The mean graft age was 9.2 years (95% CI 7.9 to 10.5),
      and 1.0 (95% CI 1 to 1) TEC cutter (2.2 mm [95% CI 2.1 to 2.3]) and 1.7 (95% CI
      1.4 to 2.0) Palmaz-Schatz coronary stents/ vein graft were used. The procedural
      success rate was 98%, with a minimal lumen diameter at baseline of 1.3 mm (95% CI
      1.1 to 1.5), increasing to 3.9 mm (95% CI 3.6 to 4.2) (p < 0.05) after the TEC
      stent procedure. Procedural complications occurred infrequently: graft
      perforation in 1 (2%) of 53 patients and distal embolization in 1 (2%) of 53
      (same patient). In-hospital complications included non-Q wave myocardial
      infarction in two patients and death after a successful procedure in three (6%)
      (n = 1 each: massive bleeding from the catheter site; sepsis; and acute
      myocardial infarction with asystole in the distribution of the stented vessel).
      The event-free survival rate to hospital discharge was 90%. Clinical follow-up
      (13 months [95% CI 11 to 15]) was available for all patients. There were five
      (11%) revascularization procedures (three bypass grafts and two percutaneous
      transluminal coronary interventions), four (9%) nonfatal myocardial infarctions
      and five (11%) deaths, for a cumulative rate of 28% for any adverse outcome
      occurring in 13 of 46 patients. CONCLUSIONS: TEC atherectomy followed by
      immediate Palmaz-Schatz coronary stenting of stenoses in old (> 9 years)
      saphenous vein grafts can be successfully performed, with a low incidence of
      procedural and hospital complications. Clinical restenosis rates are low and less
      than those previously reported; however, late morbid cardiac events are still
      frequent in this high risk group of patients. These observational findings
      suggest that this technique may improve percutaneous management of vein graft
      disease, but optimal long-term management strategies remain to be determined.

PMID- 9283523
TI  - Infrapopliteal transcatheter interventions for limb salvage in diabetic patients:
      importance of aggressive interventional approach and role of transcutaneous
      oximetry.
AB  - OBJECTIVES: This study sought to determine whether infrapopliteal transcatheter
      interventions can salvage ischemic limbs in diabetic patients referred for below
      the knee amputation at our institution. BACKGROUND: The value of transcatheter
      interventions in diabetic crural arteries is controversial. Tissue oxygen partial
      pressure (TCO2) levels < 40 mm Hg predict poor wound healing. METHODS:
      Percutaneous interventions were performed in 29 consecutive diabetic patients in
      need of limb salvage. Technical success was defined as < 20% residual vessel
      stenosis. Clinical success was defined as the avoidance of amputation and
      achievement of wound healing. At hospital discharge, patients were treated with
      Coumadin and aspirin. Ankle-brachial index (ABI) and TCO2 measurements were
      obtained before and after the intervention. RESULTS: After 12-month follow-up,
      six patients had presistent wounds, whereas 23 experienced wound healing. Forty
      of the 50 infrapopliteal arteries successfully dilated were occluded, with a mean
      (+/-SD) lesion length of 18.0 +/- 3.5 cm. After the procedure, TCO2 improved from
      27.82 +/- 9.97 mm Hg (95% confidence interval [CI] 23.95 to 31.69) to 54.5 +/-
      14.73 mm Hg (95% CI 48.79 to 60.21, p < 0.0001), whereas the ABI did not (p >
      0.2). TCO2 predicted procedural and clinical success (p < 0.0182). CONCLUSIONS:
      Infrapopliteal transcatheter interventions in diabetic patients may salvage the
      majority of limbs doomed to amputation. Although TCO2 measurements are valuable
      in predicting wound healing and success after interventions, ABI measurements are
      not.

PMID- 9283525
TI  - Clinical outcome of patients undergoing endoluminal coronary artery
      reconstruction with three or more stents.
AB  - OBJECTIVES: We sought to evaluate the outcome of patients undergoing multiple
      (three or more), contiguous stent implantation within a single native coronary
      artery. BACKGROUND: The implantation of multiple stents within a single coronary
      artery is increasing in frequency, although the outcome of such patients is not
      well described. METHODS: Forty-five patients without previous coronary artery
      bypass graft surgery (CABG) undergoing multiple, contiguous stent implantation in
      a single coronary artery were identified. Clinical and angiographic
      characteristics and outcomes were analyzed. RESULTS: The angiographic success
      rate was 97.8%. The procedural success rate was 91.1%; stent occlusion during the
      initial hospital period occurred in four patients (8.9%). Death, myocardial
      infarction (MI), CABG, repeat target vessel intervention or severe angina
      occurred in 10 (23.3%) of 43 hospital survivors at 6-months follow-up. The
      indication for stent placement was threatened or abrupt closure in 30 patients
      (66.7%). Of the 25 patients with abrupt or threatened closure whose clinical and
      angiographic data would have indicated emergent CABG had stents not been
      available, the frequency of in-hospital death and Q wave MI was similar to that
      of a matched consecutive series of patients at our institution who underwent
      emergent CABG after failed angioplasty. At 1 year, the frequency of death, Q wave
      MI, CABG and severe angina at 1 year was similar in the two groups; the need for
      repeat percutaneous intervention was more common in the stent group (25% vs. 0%,
      p = 0.01). CONCLUSIONS: Implantation of multiple, contiguous intracoronary stents
      was associated with a high initial success rate, although the incidence of early
      stent closure was relatively high. Adverse events at 6 months of follow-up were
      more frequent than previously reported for elective single-stent implantation;
      however, adverse angiographic characteristics such as dissection and thrombus
      were frequent in this group. In addition, the strategy of multiple stent
      implantation in the setting of failed angioplasty is a reasonable alternative to
      emergent CABG, although the need for further percutaneous intervention must be
      anticipated.

PMID- 9283524
TI  - Management of 219 consecutive cases of postcatheterization pseudoaneurysm.
AB  - OBJECTIVES: We attempted to evaluate nonsurgical methods of treating
      postcatheterization pseudoaneurysm. BACKGROUND: The value of reapplication of a
      compression bandage, ultrasound-guided compression repair (UGCR) and awaiting
      spontaneous thrombosis in the treatment of postcatheterization pseudoaneurysms is
      unsettled. METHODS: We followed a stepwise treatment strategy of primarily
      conservative management using 1) reapplication of a compression bandage, followed
      by 2) UGCR, if needed, and 3) observation of the natural course. Surgical repair
      was reserved for patients with a rapidly expanding or complicated lesion.
      RESULTS: Reapplication of a compression bandage was performed in 128 patients and
      was successful in 32%. The success rate correlated inversely with anticoagulant
      therapy and the size of the aneurysm. In case of failure this pretreatment with a
      compression bandage significantly enhanced the success rate of subsequent UGCR (p
      = 0.04). UGCR was performed in 124 cases with a success rate of 84%. In 54
      patients with a stable lesion, refraining from any (further) active measures
      resulted in spontaneous thrombosis of the aneurysm in 50 patients (93%) after 1
      to 180 days (median 40 days). The course of the remaining four femoral artery
      aneurysms was uneventful. Definitive repair by operation or collagen plug
      implantation was required in only 20 patients (9%). CONCLUSIONS: The first
      measure performed in the treatment of pseudoaneurysms should be reapplication of
      a compression bandage, followed, if necessary, by UGCR. After failure of UGCR,
      spontaneous healing occurs in the majority of patients. Operation can be reserved
      for progressive and complicated lesions.

PMID- 9283527
TI  - Albumin microbubble adherence to human coronary endothelium: implications for
      assessment of endothelial function using myocardial contrast echocardiography.
AB  - OBJECTIVES: We hypothesized that sonicated 5% human albumin microbubbles
      (Albunex) adhere to disrupted vascular endothelium and that this interaction is a
      marker of endothelial integrity. This study sought to identify sites and
      determinants of Albunex-endothelial cell (EC) attachment. BACKGROUND: Under
      normal conditions, Albunex microbubbles used in myocardial contrast
      echocardiography (MCE) pass unimpeded through the coronary microcirculation.
      During pathophysiologic states associated with endothelial dysfunction, however,
      microbubbles linger in the myocardium despite normal flow. The sites and
      conditions regulating microbubble adhesion are unknown. METHODS: Coverslips with
      cultured human coronary artery ECs were mounted in a parallel plate perfusion
      system and perfused with a suspension of fluorescein-labeled Albunex in culture
      medium, followed by a bubble-free wash at a wall shear rate of 100 s-1. To create
      inflammatory ECs, phorbol myristate acetate was added 4.5 h before perfusion, and
      flow cytometry was used to confirm an inflammatory response. Perfusions were
      performed under normal and inflammatory conditions using surfaces of confluent
      and subconfluent ECs and isolated extracellular matrix. Bubble adherence was
      quantified in 20 random fields per cover-slip using epifluorescent video
      microscopy. RESULTS: No microbubbles adhered to normal confluent ECs, although
      small numbers adhered to inflamed ECs (0.03 +/- 0.01 bubbles/cell, p < 0.01 vs.
      normal cells). Fever microbubbles attached to normal versus inflamed matrix of
      both partially exposed (1,800 +/- 520 vs. 4,100 +/- 1,000 bubbles/mm2, p = 0.05)
      and completely denuded (2,700 +/- 1,300 vs. 7,200 +/- 1,100 bubbles/ mm2, p <
      0.03) endothelium. CONCLUSIONS: Albunex microbubbles preferentially adhere to
      inflammatory endothelial extracellular matrix. These data suggest that MCE can be
      used to noninvasively study endothelial integrity and may have implications for
      the assessment of preclinical atherosclerotic heart disease.

PMID- 9283526
TI  - Coronary vasomotion after percutaneous transluminal coronary angioplasty depends
      on the severity of the culprit lesion.
AB  - OBJECTIVES: This study sought to evaluate coronary vasomotor response to
      percutaneous transluminal coronary angioplasty (PTCA) and its influence on
      proximal and distal vessel diameters with regard to stenosis severity and
      coronary blood flow. BACKGROUND: Coronary vasoconstriction of the distal vessel
      segment has been reported after PTCA. This vasoconstrictive effect was thought to
      be due to balloon-induced injury of the vessel wall, with release of local
      vasoconstrictors or stimulation of the sympathetic system with release of
      catecholamines, or both. METHODS: Thirty-nine patients were prospectively studied
      before and after PTCA. Patients were classified into two groups according to the
      severity of the culprit lesion: group 1 = > or = 70% to < or = 85% diameter
      stenosis (n = 23); and group 2 = > 85% to < or = 95% diameter stenosis (n = 16).
      The coronary vessel diameter of the proximal and distal vessel segments as well
      as the minimal lumen diameter were determined by quantitative coronary
      angiography. In a subgroup of 16 patients, basal and maximal coronary flow
      velocity was measured before and after PTCA with the Doppler FloWire system.
      RESULTS: The groups were comparable with regard to age, gender, serum cholesterol
      levels and medical therapy. The proximal vessel segment remained unchanged after
      PTCA in group 1 ([mean +/- SD] 0.9 +/- 3.5%, p = 0.8) but showed vasodilation in
      group 2 (+13.7 +/- 3.6%, p < 0.05). However, the distal segment showed
      vasoconstriction in group 1 (-6.7 +/- 2.0%, p < 0.01) and vasodilation in group 2
      (+31 +/- 8.0%, p < 0.01). A significant correlation was found between the change
      in distal vessel diameter after PTCA and stenosis severity (r = 0.61, p <
      0.0001). Changes in blood flow were directly correlated to stenosis severity (r =
      0.85, p < 0.002); that is, rest flow increased after PTCA in narrow lesions but
      remained unchanged in moderate lesions. The diameter changes in the distal vessel
      segment after PTCA were significantly related to flow changes (r = 0.90, p <
      0.0001). Coronary distending pressure of the distal vessel segment increased
      significantly in both groups; however, this increase was significantly greater in
      group 2 than in group 1 (55 +/- 4 vs. 14 +/- 3 mm Hg, p < 0.0001). CONCLUSIONS:
      Coronary vasomotion of the proximal and distal vessel segments after PTCA depends
      on the severity of the culprit lesion; that is, vasoconstriction of the distal
      segment is found in patients with moderate lesions and vasodilation in those with
      severe lesions. Thus, vasomotion of the post-stenotic vessel segment depends on
      the severity of the culprit lesion and is influenced by changes in coronary flow
      or distending pressure, or both.

PMID- 9283528
TI  - Pathology of unstable plaque: correlation with the clinical severity of acute
      coronary syndromes.
AB  - OBJECTIVES: The aim of this study was to relate the various clinical
      presentations of acute coronary syndromes to the underlying plaque morphology as
      assessed from histopathologic analysis of plaque fragments obtained by
      directional coronary atherectomy (DCA). BACKGROUND: Autopsy studies have shown
      that unstable angina and infarction are related to plaque instability and involve
      events such as fissure or rupture of the fibrous cap, thrombosis and
      inflammation. The clinical severity and prognosis of acute coronary syndromes can
      be estimated by the Braunwald classification of unstable angina. Whether plaque
      morphology can be related to the Braunwald classification has not been evaluated.
      METHODS: Plaque fragments were obtained by DCA in 75 patients: 38 with unstable
      angina, 19 with stable angina and 18 with no symptoms after infarction. The
      presence of fibrous tissue, thrombus, high cellularity, inflammatory cells,
      atheroma, neovessels and "stellar-shaped" smooth muscle cells was evaluated in 7
      micron thick sections by appropriate staining. The patients were classified
      according to clinical presentation without knowledge of the results of pathologic
      examination, and a plaque instability score was assigned. The risk of further
      cardiac events was classified as low, medium or high. RESULTS: Increasing
      severity of the score of unstable angina was associated with increasing
      prevalence of thrombus, high cellularity, atheroma and neovessels. Plaque from
      patients with unstable angina considered to be at low risk of further events
      appeared very similar to that of patients with stable angina, whereas the
      specific morphologic characteristics of plaque instability were more frequently
      observed as the clinical score and the risk of further events increased. After
      thrombolyzed infarction, plaque morphology depends on the delay between the acute
      event and DCA. Within 1 week after infarction, plaque still showed the
      morphologic characteristics of instability, whereas late DCA provided samples
      with morphologic features similar to those observed in patients with stable
      angina. CONCLUSIONS: The morphologic features of plaque fragments vary at
      different stages of acute coronary disease. The specific features of plaque
      instability correlate with the clinical scoring system of the Braunwald
      classification.

PMID- 9283529
TI  - Increased neopterin in patients with chronic and acute coronary syndromes.
AB  - OBJECTIVES: The aim of our study was to determine neopterin levels in patients
      with chronic and acute coronary syndromes. BACKGROUND: In chronic and acute
      coronary syndromes the release of different cytokines activates cellular defense.
      Infiltration of neutrophils and monocytes/macrophages is detected in the vessel
      wall as well as in the myocardium. Neopterin, which is a by-product of the
      guanosine triphosphate-biopterin pathway, is a marker for those activated
      macrophages. METHODS: We studied 123 subjects: 1) 21 consecutive patients (17
      men, 4 women; mean age +/- SD 66 +/- 15 years, range 31 to 87) with acute
      myocardial infarction (AMI); 2) 62 consecutive patients (50 men, 12 women; mean
      age 61 +/- 8 years, range 43 to 81) with signs and symptoms of clinically stable
      coronary artery disease (CAD); and 3) 40 healthy blood donors (28 men, 12 women;
      mean age 35 +/- 13 years). Neopterin levels were determined with a commercially
      available enzyme-linked immunosorbent assay method. RESULTS: In patients with AMI
      before thrombolytic therapy, neopterin levels were significantly higher than
      levels in patients with CAD and control subjects (13.7 vs. 8.6 and vs. 6.8
      nmol/liter, p < 0.0001). Values also differed significantly between patients with
      CAD and control subjects (p < 0.0001). Neopterin levels in patients with AMI were
      measured seven times during a 72-h period. Within-group comparison showed
      significant differences over this period (p < 0.00001). The lowest value (11.4
      nmol/liter) was observed after 4 h and differed significantly from the initial
      value and values after 24 and 72 h (p < 0.05). After 72 h, neopterin increased to
      14.9 nmol/liter, a value significantly different from all values other than the
      initial one. There was no correlation between neopterin and creatine kinase (CK);
      CK, MB isoenzyme; or lactate dehydrogenase as markers for the extent of the
      myocardial infarction during the observation period. CONCLUSIONS: Our data
      support the hypothesis of an activation of monocytes and macrophages in patients
      with an acute or chronic coronary syndrome. Neopterin as a marker for macrophage
      activation is significantly increased in patients with chronic CAD and more
      pronounced in patients with AMI shortly after the onset of symptoms.

PMID- 9283530
TI  - Use of intraaortic balloon counterpulsation in patients presenting with
      cardiogenic shock: observations from the GUSTO-I Study. Global Utilization of
      Streptokinase and TPA for Occluded Coronary Arteries.
AB  - OBJECTIVES: We sought to examine the use, complications and outcomes with early
      intraaortic balloon counterpulsation (IABP) in patients presenting with
      cardiogenic shock complicating acute myocardial infarction and treated with
      thrombolytic therapy. BACKGROUND: The use of IABP in patients with cardiogenic
      shock is widely accepted; however, there is a paucity of information on the use
      of this technique in patients with cardiogenic shock who are treated with
      thrombolytic therapy. METHODS: Patients who presented within 6 h of chest pain
      onset were randomized to one of four thrombolytic regimens. Cardiogenic shock was
      not an exclusion criterion, and data for these patients were prospectively
      collected. Patients presenting with shock were classified into early IABP
      (insertion within one calendar day of enrollment) or no IABP (insertion on or
      after day 2 or never). RESULTS: There were 68 (22%) IABP placements in 310
      patients presenting with shock. Early IABP use occurred in 62 patients (20%) and
      none in 248 (80%). Most IABP use occurred in the United States (59 of 68 IABP
      placements) involving 32% of U.S. patients presenting with shock. Despite more
      adverse events in the early IABP group and more episodes of moderate bleeding,
      this cohort showed a trend toward lower 30-day and 1-year mortality rates.
      CONCLUSIONS: IABP appears to be underutilized in patients presenting with
      cardiogenic shock, both within and outside the United States. Early IABP
      institution is associated with an increased risk of bleeding and adverse events
      but a trend toward lower 30-day and 1-year all-cause mortality.

PMID- 9283531
TI  - Thrombolytic therapy and proteolysis of factor V.
AB  - OBJECTIVES: We sought to determine the extent of Factor V proteolysis during
      thrombolytic therapy. BACKGROUND: Thrombin- or Factor Xa-activated Factor V is an
      essential cofactor in the prothrombinase complex. In purified systems, plasmin,
      the major product of thrombolytic therapy, is known to first activate then
      inactivate Factor V. METHODS: We used quantitative gel electrophoresis and
      Western blotting to analyze the cleavages in plasma Factor V after thrombolytic
      therapy. RESULTS: The addition of streptokinase to plasma resulted in the
      activation then inactivation of Factor V, confirming previous results using
      purified reagents. We also identified the Factor V fragments resulting from the
      action of thrombin and plasmin. After thrombolytic therapy, there was
      considerable Factor V cleavage. The cleavage patterns were consistent with the
      action of plasmin, with little evidence for the action of thrombin. In the Global
      Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded
      Coronary Arteries trial (n = 17), we observed an average 58% loss of intact
      Factor V at 6 h (range 1% to 91%). Samples from the Thrombolysis in Myocardial
      Infarction trial, Phase II (n = 12), collected on a shorter time scale, showed a
      loss of up to 99% at 50 min, with the loss of intact Factor V associated with the
      plasma concentration of plasminogen activator. Samples from patients with
      bleeding (n = 12) showed extensive Factor V cleavage. CONCLUSIONS: Factor V
      cleavage in thrombolytic therapy is primarily plasmin mediated, rapid and often
      extensive. It is likely that transient increases, as well as longer term losses,
      of Factor V cofactor activity play a role in both ischemic and hemorrhagic events
      subsequent to thrombolytic therapy. The extensive loss of Factor V in some
      patients may affect the estimation of heparinization.

PMID- 9283532
TI  - Impact of a comprehensive heart failure management program on hospital
      readmission and functional status of patients with advanced heart failure.
AB  - OBJECTIVES: To assess the impact of a comprehensive heart failure management
      program, functional status, hospital readmission rate and estimated hospital
      costs were determined and compared for the 6 months before and the 6 months after
      referral. BACKGROUND: The course of advanced heart failure is characterized by
      progressive clinical deterioration reflected in frequent hospital admissions,
      which comprise the major financial cost. METHODS: Over a 3-year period, 214
      patients were accepted for heart transplantation and discharged after evaluation,
      which included adjustments in medical therapy and intensive patient education.
      Patients were in New York Heart Association functional class III or IV (94 and
      120 patients, respectively), with a mean left ventricular ejection fraction of
      0.21, peak oxygen consumption of 11 ml/kg per min and a total of 429 hospital
      admissions in the previous 6 months (average 2.0 per patient). Changes in the
      medical regimen included a 98% increase in angiotensin-converting enzyme
      inhibitor dose and a flexible diuretic regimen after 4.2-liter net diuresis, with
      counseling also regarding diet and progressive exercise. RESULTS: During the 6
      months after referral, there were only 63 hospital readmissions (85% reduction),
      with 0.29/patient (p < 0.0001). Functional status improved as assessed by
      functional class (p < 0.0001) and peak oxygen consumption (15.2 vs. 11.0 ml/kg
      per min, p < 0.001). The same results were seen after excluding the 35 patients
      without full 6-month follow-up (9 deaths, 14 urgent transplant procedures during
      hospital readmission, 12 elective transplant procedures from home); 34 hospital
      admissions occurred after referral, compared with 344 before referral. Even when
      adding in the initial hospital admission after referral for these 179 patients,
      there was a 35% decrease in total hospital admissions in the 6-month period. The
      estimated savings in hospital readmission costs after subtracting the initial
      hospital costs for management was $9,800 per patient. CONCLUSIONS: Comprehensive
      heart failure management led to improved functional status and an 85% decrease in
      the hospital admission rate for transplant candidates discharged after
      evaluation. The potential to reduce both symptoms and costs suggests that
      referral to a heart failure program may be appropriate not only for potential
      heart transplantation, but also for medical management of persistent functional
      class III and IV heart failure.

PMID- 9283533
TI  - Treatment of patients admitted to the hospital with congestive heart failure:
      specialty-related disparities in practice patterns and outcomes.
AB  - OBJECTIVES: This study sought to define specialty-related differences in the care
      and outcome of patients admitted to the hospital with congestive heart failure
      (CHF). BACKGROUND: Congestive heart failure is the leading diagnosis-related
      group (DRG) discharge diagnosis in the United States and accounts for an
      estimated annual hospital cost in excess of $7 billion. The clinical impact of
      aggressive CHF management and the importance of the subspecialist in guiding this
      care have not been evaluated. METHODS: To define differences in physician
      practice patterns, we performed a chart review of consecutive patients admitted
      to a university teaching hospital with a primary DRG discharge diagnosis of CHF.
      We compared treatment and outcome of patients cared for by a generalist (n = 160)
      and those whose care was guided by a cardiologist (n = 138) during their index
      hospital period with CHF and over the next 6 months. RESULTS: At our institution,
      > 50% of patients admitted to the hospital with CHF cared for by generalists
      alone had minimal (New York Heart Association functional class I or II) symptoms,
      compared with < 15% of those cared for by a cardiologist (p < 0.01). Although
      generalists' patients underwent significantly fewer in-hospital diagnostic tests
      and had shorter lengths of stay, they had a 1.7-fold increased risk of
      readmission for CHF within 6 months (p < 0.05). Six-month cardiac and all-cause
      mortality were not significantly different between the groups. The type of
      physician caring for the patient and a history of diabetes, previous CHF or
      myocardial infarction were independent predictors of readmission for CHF.
      CONCLUSIONS: Involvement of a cardiologist in the care of patients admitted to
      the hospital with CHF is associated with increased use of diagnostic testing,
      longer hospital stays and improved clinical outcome. These results substantiate
      practice guidelines that suggest a role for cardiologists in the care of
      symptomatic patients with CHF.

PMID- 9283534
TI  - Effect of continuous positive airway pressure on mitral regurgitant fraction and
      atrial natriuretic peptide in patients with heart failure.
AB  - OBJECTIVES: We sought to determine the effects of continuous positive airway
      pressure (CPAP) on mitral regurgitant fraction (MRF) and plasma atrial
      natriuretic peptide (ANP) concentration in patients with congestive heart failure
      (CHF). BACKGROUND: In patients with CHF, elevated plasma ANP concentration is
      associated with elevated cardiac filling pressures. Secondary mitral
      regurgitation may contribute to elevation in plasma ANP concentration in patients
      with CHF. Because CPAP reduces transmural cardiac pressures and left ventricular
      (LV) volume, we hypothesized that long-term CPAP application would decrease the
      MRF and plasma ANP concentration in patients with CHF and Cheyne-Stokes
      respiration with central sleep apnea (CSR-CSA). METHODS: Seventeen patients with
      CHF and CSR-CSA underwent baseline assessments of plasma ANP concentration and
      left ventricular ejection fraction (LVEF) and MRF by radionuclide angiography.
      They were then randomized to receive nocturnal CPAP plus optimal medical therapy
      (n = 9) or optimal medical therapy alone (n = 8) for 3 months and were then
      reassessed. RESULTS: In the CPAP-treated group, LVEF increased from (mean +/-SEM)
      20.2 +/- 4.2% to 28.2 +/- 5.3% (p < 0.02); MRF decreased from 32.8 +/- 7.7% to
      19.4 +/- 5.5% (p < 0.02); and plasma ANP concentration decreased from 140.9 +/-
      20.8 to 103.9 +/- 17.0 pg/ml (p < 0.05). The control group experienced no
      significant changes in LVEF, MRF or plasma ANP concentration. Among all patients,
      the change in plasma ANP concentration from baseline to 3 months correlated
      significantly with the change in MRF (r = 0.789, p < 0.0002). CONCLUSIONS: In
      patients with CHF, CPAP-induced reductions in MRF and plasma ANP concentration in
      association with improvements in LVEF indicate improved cardiac mechanics. Our
      findings also suggest that reductions in plasma ANP concentration were at least
      partly due to reductions in MRF.

PMID- 9283535
TI  - Optimizing timing of surgical correction in patients with severe aortic
      regurgitation: role of symptoms.
AB  - OBJECTIVES: We sought to determine the independent effect of preoperative
      symptoms on survival after surgical correction of aortic regurgitation (AR).
      BACKGROUND: Aortic valve replacement for severe AR is recommended after New York
      Heart Association functional class III or IV symptoms develop. However, whether
      severe preoperative symptoms have a negative influence on postoperative survival
      remains controversial. METHODS: Preoperative characteristics and postoperative
      survival in 161 patients with functional class I or II symptoms (group 1) were
      compared with those in 128 patients with class III or IV symptoms (group 2)
      undergoing surgical repair of severe isolated AR between 1980 and 1989. RESULTS:
      Compared with group 1, group 2 patients were older (p < 0.0001), were more often
      female (p = 0.001) and more often had a history of hypertension (p = 0.001),
      diabetes mellitus (p = 0.029) or myocardial infarction (p = 0.005) and were more
      likely to require coronary artery bypass graft surgery (p < 0.0001). The
      operative mortality rate was higher in group 2 (7.8%) than in group 1 (1.2%, p =
      0.005), and the 10-year postoperative survival rate was worse (45% +/- 5% [group
      2] vs. 78% +/- 4% [group 1], p < 0.0001). Compared with age- and gender-matched
      control subjects, long-term postoperative survival was similar to that expected
      in group 1 (p = 0.14) but significantly worse in group 2 (p < 0.0001). On
      multivariate analysis, functional class III or IV symptoms were significant
      independent predictors of operative mortality (adjusted odds ratio 5.5, p =
      0.036) and worse long-term postoperative survival (adjusted hazard ratio 1.81, p
      = 0.0091). CONCLUSIONS: In the setting of severe AR, preoperative functional
      class III or IV symptoms are independent risk factors for excess immediate and
      long-term postoperative mortality. The presence of class II symptoms should be a
      strong incentive to consider immediate surgical correction of severe AR.

PMID- 9283536
TI  - Planimetry and transthoracic two-dimensional echocardiography in noninvasive
      assessment of aortic valve area in patients with valvular aortic stenosis.
AB  - OBJECTIVES: The aim of this study was to evaluate the reliability of
      transthoracic two-dimensional echocardiography in measuring aortic valve area
      (AVA) by planimetry. BACKGROUND: Planimetry of AVA using two-dimensional
      transesophageal echocardiographic images has been reported to be a reliable
      method for measuring AVA in patients with aortic stenosis. Recent advances in
      resolution of two-dimensional echocardiography permit direct visualization of an
      aortic valve orifice from the transthoracic approach more easily than before.
      METHODS: Forty-two adult patients with valvular aortic stenosis were examined. A
      parasternal short-axis view of the aortic valve was obtained with transthoracic
      two-dimensional echocardiography. AVA was measured directly by planimetry of the
      inner leaflet edges at the time of maximal opening in early systole. AVA was also
      measured by planimetry using transesophageal echocardiography, by the continuity
      equation and by cardiac catheterization (Gorlin formula). RESULTS: In 32 (76%) of
      the 42 study patients, AVA could be detected by using the transthoracic
      planimetry method. There were good correlations between results of transthoracic
      two-dimensional echocardiographic planimetry and the continuity equation (y =
      0.90x + 0.09, r = 0.90, p < 0.001, SEE = 0.09 cm2), transesophageal
      echocardiographic planimetry (y = 1.05x - 0.02, r = 0.98, p < 0.001, SEE = 0.04
      cm2) and the Gorlin formula (y = 1.02x + 0.05, r = 0.89, p < 0.001, SEE = 0.10
      cm2). CONCLUSIONS: Transthoracic two-dimensional echocardiography provides a
      feasible and reliable method in measuring AVA in patients with aortic stenosis.

PMID- 9283537
TI  - Differences in myocardial velocity gradient measured throughout the cardiac cycle
      in patients with hypertrophic cardiomyopathy, athletes and patients with left
      ventricular hypertrophy due to hypertension.
AB  - OBJECTIVES: We sought to compare the myocardial velocity gradient (MVG) measured
      across the left ventricular (LV) posterior wall during the cardiac cycle between
      patients with hypertrophic cardiomyopathy (HCM), athletes and patients with LV
      hypertrophy due to systemic hypertension and to determine whether it might be
      used to discriminate these groups. BACKGROUND: The MVG is a new ultrasound
      variable, based on the color Doppler technique, that quantifies the spatial
      distribution of transmyocardial velocities. METHODS: A cohort of 158 subjects was
      subdivided by age into two groups: Group I (mean [+/-SD] 30 +/- 7 years) and
      Group II (58 +/- 8 years). Within each group there were three categories of
      subjects: Group Ia consisted of patients with HCM (n = 25), Group Ib consisted of
      athletes (n = 21), and Group Ic consisted of normal subjects; Group IIa consisted
      of patients with HCM (n = 19), Group IIb consisted of hypertensive patients (n =
      27), and Group IIc consisted of normal subjects (n = 33). RESULTS: The MVG (mean
      [+/-SD] s-1) measured in systole was lower (p < 0.01) in patients with HCM (Group
      Ia 3.2 +/- 1.1; Group IIa 2.9 +/- 1.2) compared with athletes (Group Ib 4.6 +/-
      1.1), hypertensive patients (Group IIb 4.2 +/- 1.8) and normal subjects (Group Ic
      4.4 +/- 0.8; Group IIc 4.8 +/- 0.8). In early diastole, the MVG was lower (p <
      0.05) in patients with HCM (Group Ia 3.7 +/- 1.5; Group IIa 2.6 +/- 0.9) than in
      athletes (Group Ib 9.9 +/- 1.9) and normal subjects (Group Ic 9.2 +/- 2.0; Group
      IIc 3.6 +/- 1.5), but not hypertensive patients (Group IIb 3.3 +/- 1.3). In late
      diastole, the MVG in patients with HCM (Group Ia 1.3 +/- 0.8; Group IIa 1.4 +/-
      0.8) was lower (p < 0.01) than that in hypertensive patients (Group IIb 4.3 +/-
      1.7) and normal subjects (Group IIc 3.8 +/- 0.9). An MVG < or = 7 s-1, as a
      single diagnostic approach, differentiated accurately (0.96 positive and 0.94
      negative predictive value) between patients with HCM and athletes when the
      measurements were taken during early diastole. CONCLUSIONS: In both age groups,
      the MVG was lower in both systole and diastole in patients with HCM than in
      athletes, hypertensive patients or normal subjects. The MVG measured in early
      diastole in a group of subjects 18 to 45 years old would appear to be an accurate
      variable used to discriminate between HCM and hypertrophy in athletes.

PMID- 9283538
TI  - Conscious sedation with combined hypnotic agents for implantation of implantable
      cardioverter-defibrillators.
AB  - OBJECTIVES: The objective of this study was to evaluate the feasibility, safety
      and efficacy of placing implantable cardioverter-defibrillators (ICDs) in the
      electrophysiology laboratory using conscious sedation with combined hypnotic
      agents and deep sedation with etomidate. BACKGROUND: Implantable cardioverter
      defibrillators with transvenous leads permit the use of simplified implantation
      techniques similar to those used for the insertion of permanent pacemakers.
      However, implantation of ICDs without general anesthesia has thus far gained
      limited acceptance. METHODS: In 162 patients, conscious sedation during ICD
      placement was achieved with combined intravenous midazolam, morphine and
      promethazine (Phenergan). Intravenous etomidate was administered to induce deep
      sedation for defibrillation threshold testing. First-time implantations were in
      the prepectoral position (n = 142), but some patients with preexisting devices
      received abdominal implants (n = 20). The results were compared with those of
      concurrent patients (n = 56) who received prepectoral implants under propofol
      anesthesia administered by an attending anesthesiologist. RESULTS: The anesthetic
      protocol was implemented without major intraoperative complications. During deep
      sedation with etomidate, episodes of apnea, hypoxia or arterial hypotension
      requiring therapeutic intervention did not occur. During a mean (+/-SD) follow-up
      period of 257 +/- 140 days (median 227, range 14 to 482), there were, among the
      162 patients, a total of two nonsudden cardiac deaths-one 71 days and the other
      157 days after the operation. There were two nonsudden deaths in the concurrent
      control subjects (n = 56)-one 13 days and the other 110 days after the operation.
      CONCLUSIONS: Implantation of ICDs under conscious sedation with combined hypnotic
      agents and deep sedation with etomidate is a safe and effective procedure with
      low perioperative morbidity and low long-term complication rates.

PMID- 9283539
TI  - Electrocardiographic repolarization during stress from awakening on alarm call.
AB  - OBJECTIVES: The present study aimed to characterize the electrocardiographic
      features of cardiac repolarization during an arousal reaction in healthy
      subjects. BACKGROUND: Electrocardiographic ST segments and T waves may indicate
      the activity of cardiac autonomic nervous control. Abnormal dynamics of
      repolarization are considered to reveal susceptibility to cardiac arrhythmias.
      Responses in normal subjects may help to understand the effects on patients'
      arrhythmias. METHODS: Ambulatory electrocardiography was performed in 30 healthy
      physicians during emergency calls while they were on duty in the hospital.
      Samples were taken before and during the 1st 30 s after the calls. Polarity of
      the T wave and ST segment depression were determined. The QT interval and the
      cardiac cycle length (CL) were measured, and their relation (QT/CL slope) was
      calculated. For comparison, the QT interval was also measured in stable
      conditions at specified heart rates of 60 to 110 beats/min. RESULTS: During
      arousal, the T wave was inverted in 19 subjects (63%) and the ST segment
      depressed > or = 0.1 mV in 10 (33%). The proportional duration of the terminal T
      wave also varied. The time course of these alterations followed the change in
      heart rate. During the strongest arousal reaction, the heart rate increased from
      55 +/- 7 to 112 +/- 18 beats/min (mean +/-SD) and reached maximum at 17s on
      average. The QT interval shortened only slightly and was on average 59 to 67 ms
      longer (p < 0.001) than that at similar heart rates during stable conditions. The
      QT/CL slope was almost horizontal, 0.085 +/- 0.061, during arousal and much
      steeper, 0.168 +/- 0.055 (p < 0.001), during stable conditions. CONCLUSIONS:
      Derangements in the T wave and ST segment as signs of sympathetic overactivity
      are common during arousal and are associated with marked inertia in QT interval
      adaptation. These modifications of ventricular repolarization may mediate the
      generation of stress-provoked arrhythmias in electrically unstable hearts.

PMID- 9283540
TI  - Diagnostic accuracy of transesophageal echocardiography during cardiopulmonary
      resuscitation.
AB  - OBJECTIVES: We sought to establish the diagnostic accuracy of transesophageal
      echocardiography (TEE) during cardiopulmonary resuscitation. BACKGROUND: Because
      of its bedside diagnostic capabilities, excellent cardiac images and lack of
      interference with resuscitation efforts, TEE is ideally suited to determine the
      cause of a circulatory arrest that is not due to severe arrhythmia. However, the
      diagnostic accuracy of TEE during resuscitation is unknown. METHODS: TEE was
      performed in patients with prolonged circulatory arrest. The TEE diagnoses were
      compared with diagnoses from autopsy, surgery and clinical follow-up. RESULTS: Of
      the 48 study patients (29 male, 19 female, mean age +/- SD 61 +/- 20 years), 28
      had an in-hospital cardiac arrest and 20 an out-of-hospital onset of arrest.
      Forty-four patients eventually died; four survived to discharge. The diagnoses
      made with TEE were cardiac tamponade (n = 6), myocardial infarction (n = 21),
      pulmonary embolism (n = 6), ruptured aorta (n = 1), aortic dissection (n = 4),
      papillary muscle rupture (n = 1), other diagnosis (n = 2) and absence of
      structural cardiac abnormalities (n = 7). A definite diagnosis from a reference
      standard was available in 31 patients. The TEE diagnosis was confirmed in 27 of
      the 31-by postmortem examination (n = 19), operation (n = 2), angiography (n = 2)
      or clinical course (n = 4). In the other four patients the TEE diagnosis proved
      incorrect by postmortem examination. The sensitivity, specificity and positive
      predictive value of TEE were 93%, 50% and 87%, respectively. In 15 patients
      (31%), major therapeutic decisions were based on TEE findings. CONCLUSIONS: TEE
      can reliably establish the cause of a circulatory arrest during cardiopulmonary
      resuscitation.

PMID- 9283541
TI  - Papillary fibroelastoma: echocardiographic characteristics for diagnosis and
      pathologic correlation.
AB  - OBJECTIVES: We sought to determine the clinical and echocardiographic
      characteristics of papillary fibroelastoma (PFE). BACKGROUND: PFE is a rarely
      encountered cardiac tumor about which relatively little is known. METHODS:
      Institutional records were reviewed for the years 1980 to 1995 for patients with
      pathologic or echocardiographic diagnosis of PFE. Group 1 included 17 patients
      with the pathologic diagnosis of PFE who also underwent echocardiography.
      Echocardiographic features of PFE were established in group 1. Group 2 included
      37 patients with only echocardiographic evidence of PFE. RESULTS: In group 1, 7
      (41.2%) of 17 patients had symptoms related to PFE. Neurologic events occurred in
      5 (29.4%) of 17 patients. All patients had the tumor surgically removed. During
      follow-up, no new embolic events occurred. Echocardiographic characteristics of
      PFE included a small tumor (12.1 +/- 6.5 x 9.0 +/- 4.3 mm), usually pedunculated
      (14 [94%] of 17 patients) and mobile, with a homogeneous speckled pattern and a
      characteristic stippling along the edges. PFEs were most common on valvular
      surfaces (12 [60%] of 20 PFEs) but were not uncommon on other endocardial
      surfaces (8 [40%] of 20 PFEs). The tumor did not cause valvular dysfunction. In
      group 2, 16 (43%) of 37 patients were asymptomatic. Five patients (13.5%) had a
      previous neurologic event. During follow-up (mean 31 months, range 1 to 77), nine
      neurologic events occurred. CONCLUSIONS: PFEs are associated with embolism, can
      be diagnosed with echocardiography, are often an incidental clinical finding and
      do not cause valvular dysfunction.

PMID- 9283542
TI  - Adverse effects of low dose amiodarone: a meta-analysis.
AB  - OBJECTIVES: We sought to assess the odds of experiencing adverse effects with low
      dose amiodarone therapy compared with placebo. BACKGROUND: An estimate of the
      likelihood of experiencing amiodarone-related adverse effects with exposure to
      low daily doses of the drug is lacking in the published reports, and little
      information is available on adverse effect event rates in control groups not
      receiving the drug. METHODS: Data from four published trials involving 1,465
      patients were included in a meta-analysis design. The criteria for inclusion were
      1) double-blind, placebo-controlled design; 2) absence of a crossover design
      between patient groups; 3) mean follow-up of at least 12 months; 4) maintenance
      amiodarone dose < or = 400 mg/day; and 5) presence of an explicit description of
      adverse effects. Data were pooled after testing for homogeneity of treatment
      effects across trials, and summary odds ratios were calculated by the Peto
      modified Mantel-Haenszel method for each adverse effect. RESULTS: The mean
      amiodarone dose per day ranged from 152 to 330 mg; 738 patients were randomized
      to receive amiodarone and 727 placebo. Exposure to amiodarone in this dose range,
      for a minimal duration of 12 months, resulted in odds similar to those of placebo
      for hepatic and gastrointestinal adverse effects, but in significantly higher
      odds than those of placebo (p < 0.05) for experiencing thyroid (odds ratio [OR]
      4.2, 95% confidence interval [CI] 2.0 to 8.7), neurologic (OR 2.0, 95% CI 1.1 to
      3.7), skin (OR 2.5, 95% CI 1.1 to 6.2), ocular (OR 3.4, 95% CI 1.2 to 9.6) and
      bradycardic (OR 2.2, 95% CI 1.1 to 4.3) adverse effects. A trend toward increased
      odds of pulmonary toxicity was noted (OR 2.0, 95% CI 0.9 to 5.3), but this did
      not reach statistical significance (p = 0.07). The unadjusted total incidence of
      drug discontinuation was 22.9% in the amiodarone group and 15.4% in the placebo
      group. The odds of discontinuing the drug in the amiodarone group was
      approximately 1.5 times that of the placebo group (OR 1.52, 95% CI 1.2 to 1.9) (p
      = 0.003). CONCLUSIONS: Compared with placebo, there is a higher likelihood of
      experiencing several amiodarone-related adverse effects with exposure to low
      daily doses of the drug. Thus, although low dose amiodarone may be well
      tolerated, it is not free of adverse effects.

PMID- 9283543
TI  - Adverse effects of amiodarone at low dose: plus ca change.

PMID- 9283544
TI  - Freehand three-dimensional echocardiography for measurement of left ventricular
      mass: in vivo anatomic validation using explanted human hearts.
AB  - OBJECTIVES: We sought to validate freehand three-dimensional echocardiography for
      measuring left ventricular mass and to compare its accuracy and variability with
      those of conventional echocardiographic methods. BACKGROUND: Accurate measurement
      of left ventricular mass is clinically important as a predictor of morbidity and
      mortality. Freehand three-dimensional echocardiography eliminates geometric
      assumptions used by conventional methods, minimizes image positioning errors
      using a line of intersection display and increases sampling of the ventricle.
      Preliminary studies have shown it to have high accuracy and low variability.
      METHODS: Twenty-eight patients awaiting heart transplantation were examined by
      conventional and freehand three-dimensional echocardiography. Left ventricular
      mass was determined by the M-mode ("Penn-cube") method, the two-dimensional
      truncated ellipsoid method and three-dimensional surface reconstruction. The
      ventricles of 20 explanted hearts were obtained, trimmed and weighed.
      Echocardiographic mass by each method was compared with true mass by linear
      regression. Accuracy, bias and interobserver variability were calculated.
      RESULTS: For three-dimensional echocardiography, the correlation coefficient,
      standard error of the estimate, root mean square percent error (accuracy), bias
      and interobserver variability were 0.992, 11.9 g, 4.8%, -4.9 g and 11.5%,
      respectively. For the two-dimensional truncated ellipsoid method they were 0.905,
      38.5 g, 15.6%, 15.4 g and 23.3%. For the M-mode ("Penn-cube") method they were
      0.721, 96.9 g, 53.0%, 109.2 g and 19.5%. CONCLUSIONS: Freehand three-dimensional
      echocardiography for measurement of left ventricular mass has high accuracy and
      low variability and is superior to conventional methods in hearts of abnormal
      size and geometry.

PMID- 9283545
TI  - Balloon angioplasty of recurrent coarctation: a 12-year review.
AB  - OBJECTIVES: This study was undertaken to investigate the long-term outcome of
      balloon angioplasty for recurrent coarctation of the aorta in a large series of
      patients. BACKGROUND: Balloon angioplasty has become the standard treatment for
      residual or recurrent aortic coarctation. Despite the widespread use of this
      treatment modality, there are few data outlining the long-term outcome of a large
      patient cohort. METHODS: Clinical, echocardiographic, hemodynamic and
      angiographic data on 90 consecutive patients who underwent balloon angioplasty
      between January 1984 and January 1996 were reviewed. RESULTS: Mean systolic
      pressure gradients were reduced from 31 +/- 21 to 8 +/- 9 mm Hg after dilation (p
      = 0.0001). The mean diameter of the stenotic site, measured in the frontal and
      lateral views, increased by 38% and 35%, respectively (p = 0.001). Neurologic
      events occurred in two patients, with one death. An aortic tear occurred in one
      patient, requiring surgical intervention. Optimal results were defined as a
      postprocedure gradient < 20 mm Hg and were obtained acutely in 88% of patients.
      At long-term follow-up (12 years), 53 (72%) of 74 patients with an early optimal
      result remained free from reintervention. Transverse arch hypoplasia, defined as
      an arch dimension < 2 SD below the mean for age, was the primary predictor of the
      need for reintervention. CONCLUSIONS: Although the majority of patients
      undergoing percutaneous balloon angioplasty for recoarctation of the aorta will
      achieve long-term benefit, the need for further surgical intervention in those
      with transverse arch hypoplasia remains high.

PMID- 9283546
TI  - Systemic venous collateral channels causing desaturation after bidirectional
      cavopulmonary anastomosis: evaluation and management.
AB  - OBJECTIVES: We sought to characterize the frequency, anatomic details and factors
      associated with the development of collateral channels between the superior and
      inferior vena caval systems after bidirectional cavopulmonary anastomosis.
      BACKGROUND: It is well known that systemic venous collateral channels often
      develop in patients who have undergone a classic Glenn shunt or bidirectional
      cavopulmonary anastomosis and that such collateral channels can lead to profound
      systemic desaturation. However, there have been few reports focusing on this
      problem. METHODS: Fifty-four patients (median age 1.4 years) who underwent
      bidirectional cavopulmonary anastomosis and had preoperative and postoperative
      angiograms available for review were studied retrospectively. Postoperative
      connections between the superior and inferior vena caval systems were identified
      and measured. Sites of collateral origin and entry from the superior and inferior
      venous systems, as well as the course taken in between, were recorded. RESULTS:
      At follow-up angiography performed 17 days to 46 months postoperatively, a total
      of 31 venous collateral channels were observed in 18 patients with a wide variety
      of primary morphologic diagnoses. The majority of these collateral channels (80%)
      originated from the brachiocephalic vein or its junction with the superior vena
      cava, and over half of them drained below the diaphragm. In patients who
      developed venous collateral channels, the mean transpulmonary pressure gradient
      early after bidirectional cavopulmonary anastomosis was higher (p = 0.005), and
      mean arterial oxygen saturation at follow-up was lower (p = 0.009). There were
      trends toward higher superior vena caval pressure early after the operation and
      at follow-up in patients with collateral channels and a higher likelihood of
      absent upper lobe pulmonary blood flow in these patients. Successful coll
      embolization of 10 collateral channels was performed in six patients, with a
      median increase in arterial oxygen saturation of 16%. CONCLUSIONS:
      Angiographically detectable systemic venous collateral channels develop after
      bidirectional cavopulmonary anastomosis in a substantial number of patients (33%
      in the present series) with a variety of forms of a functional univentricular
      heart. Patients with venous collateral channels can be treated successfully with
      coil embolization, but the indications for embolization will depend on individual
      circumstances.

PMID- 9283547
TI  - Impact of volume loading and load reduction on ventricular refractoriness and
      conduction properties in canine congestive heart failure.
AB  - OBJECTIVES: This investigations was undertaken to examine the alteration of
      electrophysiologic properties, including refractoriness, strength-interval
      relations and conduction, with the development of heart failure and to
      characterize the impact of volume loading on these indexes in the cardiomyopathic
      setting. METHODS: Electrophysiologic properties in eight dogs with pacing-induced
      dilated cardiomyopathy were compared with those in six control dogs before and
      after rapid infusion of 800 ml of intravenous saline. RESULTS: The right
      ventricular (RV) and left ventricular (LV) effective refractory period (ERP) and
      absolute refractory period (ARP) were significantly longer in dogs with pacing
      induced cardiomyopathy than in control dogs: RV ERP 181 +/- 11 ms versus 138 +/-
      7 ms (mean +/- SD) (p < 0.0001) and anterior LV ERP 177 +/- 13 ms versus 128 +/-
      11 ms (p < 0.0001), respectively; ARP 159 +/- 14 ms versus 114 +/- 7 ms (p <
      0.0001) at the RV site and 153 +/- 12 versus 117 +/- 5 ms (p < 0.0001) at the
      anterior LV site. After volume loading in cardiomyopathic animals, posterior and
      anterior LV ERPs became prolonged to 178 +/- 5 ms (p = 0.004) and 189 +/- 14 ms
      (p = 0.065), respectively, shifting the strength-interval relation in the
      direction of longer S1S2 coupling intervals. Anterior LV monophasic action
      potential durations at 90% repolarization also became prolonged from 192 +/- 10
      ms to 222 +/- 23 ms (p < 0.012) with volume loading. These findings were not
      altered by subsequent sodium nitroprusside. Local conduction times parallel and
      perpendicular to fiber orientation were not altered by development of
      cardiomyopathy or volume alterations. CONCLUSIONS: The development of dilated
      cardiomyopathy results in significant prolongation of refractoriness and
      repolarization that is increased further by volume augmentation but is not
      reversed by pharmacologic load reduction. Although these abnormalities may
      contribute to the environment needed for a non-reentrant, triggered or stretch
      mediated arrhythmogenic process in cardiomyopathic states, additional studies
      will be required to demonstrate such a focal mechanism conclusively.

PMID- 9283549
TI  - Why would anyone want to become a cardiologist these days?

PMID- 9283550
TI  - Education--the foundation and future of the ACC.

PMID- 9283548
TI  - Calculation of aortic regurgitant volume by a new digital Doppler color flow
      mapping method: an animal study with quantified chronic aortic regurgitation.
AB  - OBJECTIVES: The aim of the present study was to quantitate aortic regurgitant
      volume and regurgitant fraction in a chronic animal model with surgically created
      aortic regurgitation using a new semiautomated color Doppler flow calculation
      method. BACKGROUND: The conventional noninvasive methods for evaluating the
      severity of aortic regurgitation have not been accepted widely nor compared with
      truly quantitative reference standards. METHODS: Eight to 20 weeks after aortic
      regurgitation was surgically induced in six sheep, a total of 22 hemodynamic
      states were studied. Electromagnetic flow probes and meters provided reference
      flow data. Epicardial color Doppler echocardiographic studies were performed to
      image left ventricular outflow tract forward and aortic regurgitant blood flows.
      The new method digitally integrated spatial and temporal color flow velocity data
      for left ventricular outflow tract forward flow and ascending aortic regurgitant
      flow. The pulsed Doppler method using the velocity-time integral was also used to
      obtain regurgitant volumes and regurgitant fractions. RESULTS: Regurgitant
      volumes and regurgitant fractions by the new method agreed well with those
      obtained electromagnetically, whereas the pulsed Doppler method overestimated
      these reference data (mean [+/-SD] difference 0.23 +/- 2.9 ml vs. 11 +/- 5.8 ml,
      p < 0.0001 for regurgitant volume; mean difference 1.2 +/- 7.6% vs. 19 +/- 13%, p
      < 0.0001 for regurgitant fraction). CONCLUSIONS: This animal study, using
      strictly quantified aortic regurgitant volumes, demonstrated that the digital
      color Doppler method provides accurate aortic regurgitant volumes and regurgitant
      fractions without cumbersome measurements.

PMID- 9283551
TI  - Effect of lip adhesion on labial height in two-stage repair of unilateral
      complete cleft lip.
AB  - A lip-adhesion procedure before definitive repair of unilateral complete cleft
      lip has been widely used but rarely analyzed over the past 25 years. This report
      is a quantitative prospective assessment of one possible benefit of lip adhesion,
      an increased vertical height of the cleft labial elements. Lip adhesion was
      performed on 43 consecutive infants with unilateral complete cleft of the primary
      palate. Markings for rotation-advancement repair were placed before lip adhesion
      and again at the time of the complete nasolabial correction. Using a standardized
      caliper, anthropometric measurements of the vertical height of the medial and
      lateral lip elements were made from these markings. The relative increase in
      vertical height of the medial and lateral labial segments during the mean
      interoperative interval of 3.2 months was calculated. Analysis of these
      measurements revealed a small disproportionate increase in vertical lip height of
      the cleft side compared with the normal side after lip adhesion. Discrepancy of
      the lateral lip height between the cleft and noncleft sides decreased from 3.0 to
      2.7 mm (10 percent, p = 0.05), and the prolabial or medial height discrepancy
      decreased from 3.4 to 2.8 mm (17 percent, p < 0.01). Subgroup analysis of infants
      whose adhesion was done either at a young age, without premaxillary orthopedics,
      or with an intact secondary palate, revealed no statistically significant
      improvement in the labial height measures. It is arguable whether the small
      relative increase in height of the medial and lateral cleft elements justifies
      lip adhesion before definitive repair of unilateral complete cleft lip.

PMID- 9283552
TI  - Transantral endoscopic orbital floor exploration: a cadaver and clinical study.
AB  - A cadaver and clinical study was performed to determine the value of transantral
      endoscopy in diagnosis and treatment of orbital floor fractures. Six fresh
      cadaver heads were dissected using a 30 degree, 4-mm endoscope through a 1 cm2
      antrotomy. In the cadaver, the orbital floor and the course of the infraorbital
      nerve were easily identified. The infraorbital nerve serves as a reference point
      for evaluation of fracture size; three zones of the floor are described that are
      oriented relative to the infraorbital nerve. In the clinical study, nine patients
      with orbital floor fracture initially underwent endoscopy at the time of fracture
      repair: three patients had comminuted zygomatico-orbital fractures, five had
      monofragmented tetrapod fractures, and one had an isolated orbital blowout
      fracture. Endoscopic dissection of the orbital fractures revealed seven fractures
      with an area > 2 cm2 and two fractures with an area of < 2 cm2. The isolated
      orbital floor blowout fracture had entrapped periorbital tissue, which was
      completely reduced endoscopically. A separate patient with a < 2 cm2 displaced
      fracture also had stable endoscopic reduction. In the remaining seven patients,
      the endoscopic technique assisted with the floor reconstruction by identifying
      the precise fracture configuration as well as identifying the stable posterior
      ledge of the orbital floor fracture. There have been no complications in any of
      our patients to date. We conclude: (1) Transantral orbital floor exploration
      allows precise determination of orbital floor fracture size, location, and the
      presence of entrapped periorbita. The information obtained through endoscopic
      techniques may be used to select patients who would not benefit from lid
      approaches to the orbital floor and may possibly eliminate nontherapeutic
      exploration. (2) Transantral endoscopic orbital floor exploration assists the
      reduction of complex orbital floor fractures and allows precise identification of
      the posterior shelf for implant placement. (3) Transantral endoscopic techniques
      can completely reduce entrapped periorbital tissue caught in a trapdoor type of
      fracture.

PMID- 9283553
TI  - Arterial anatomy of the oral cavity: an analysis of vascular territories.
AB  - Knowledge of the specific cutaneous or surface regions supplied by constant named
      arterial sources has allowed for increasing clinical application of flap
      transfers of tissue. Despite the routine use of intraoral flaps for
      reconstruction of congenital or acquired defects of the oral cavity and pharynx,
      no previous investigation has centered on understanding the surface or mucosal
      arterial territories of the oral cavity. In a cadaver study, six mucosal
      territories of the intraoral cavity were defined using selective ink and lead
      oxide injections through named arteries. The anatomical boundaries of these
      territories are predictable and constant in location for different cadavers. The
      six contiguous territories are based on the buccal, labial, inferior alveolar,
      ascending palatine, ascending pharyngeal, and lingual arteries. This study
      supports the safe vascular basis of existing clinical procedures of the intraoral
      cavity and may have implications for the design of new intraoral reconstructive
      procedures.

PMID- 9283554
TI  - Sentinel lymph node biopsy in melanoma of the head and neck.
AB  - BACKGROUND: The sentinel lymph node is the first node or nodes to drain a
      cutaneous melanoma. Sentinel lymph node biopsy is performed to determine whether
      regional metastases are present. The authors' experience with the new technique
      of sentinel lymph node biopsy for melanoma of the head and neck is reported.
      PATIENTS AND METHODS: During the period of January of 1992 to December of 1995,
      58 consecutive patients were identified from the melanoma database who had
      localization of the sentinel lymph node for primary cutaneous melanoma of the
      head and neck. Techniques for identification of the sentinel node(s) include
      preoperative lymphoscintigraphy and intraoperative Lymphazurin dye (vital blue
      dye) and technetium-99m-labeled sulfur colloid injection around the primary tumor
      site with Neoprobe mapping. RESULTS: Fifty-eight patients (13 female, 45 male),
      mean age 61 years, with melanoma of the head and neck with a mean Breslow
      thickness of 2.21 mm. (range, 0.82-6.87 mm.) and no regional lymphadenopathy
      underwent sentinel node mapping. The sentinel node was successfully identified in
      55 patients (95 percent). Blue dye was visualized in 85 of 126 sentinel nodes
      excised (67 percent), whereas the remainder of the sentinel nodes were localized
      with the Neoprobe. Forty-nine patients who had successful mapping and sentinel
      node biopsy had no evidence of metastatic disease in the sentinel node or other
      nodes in the basin. Six of the fifty-five patients (11 percent) had evidence of
      micrometastatic disease, and all six had the sentinel node as the only site of
      metastasis. Five of six patients with micrometastases had a subsequent neck
      dissection and/or superficial parotidectomy. None of these patients had evidence
      of "skip metastases" with a negative sentinel node and higher level nodes
      positive for metastases. In total, 6 of the 18 sentinel nodes (33 percent)
      identified in these six patients contained micrometastatic disease, whereas none
      of the 139 other nodes sampled had any evidence of metastases. The exact
      probability that all six unpaired observations would consist of involvement of
      only the sentinel nodes is p = 0.0312. CONCLUSIONS: By combining the two mapping
      techniques in patients with melanoma of the head and neck, the sentinel node(s)
      can be mapped and identified individually, similar to melanoma in other
      locations. The sentinel nodes have been shown to contain the first evidence of
      regional metastatic melanoma. This staging information can be used to plan
      therapeutic node dissections and adjuvant therapy that may have a survival
      benefit in patients with stage III melanoma of the head and neck. Lymphatic
      mapping can be used to make the surgical care of the melanoma patient more
      conservative, so that only those patients with solid evidence of regional node
      metastases are subjected to the morbidity and expense of a complete node
      dissection and the toxicities of adjuvant therapy.

PMID- 9283555
TI  - Outcome study of the psychological changes after silicone breast implant removal.
AB  - INTRODUCTION: The purpose of this longitudinal study is to determine if there are
      changes in psychological well-being after breast implant removal. METHODS: Thirty
      seven women underwent breast implant removal and completed a preoperative
      baseline, early postoperative (4 to 9 months), and late postoperative (> 10
      months) Brief Symptom Inventory, a measure of psychological distress. RESULTS:
      After breast implant removal the mean Global Severity Scores on the Brief Symptom
      Inventory of women undergoing implant removal increased over the three time
      periods, indicating increasing psychological distress. When the group was divided
      into those who had breast reconstruction after implant removal (implant
      replacement with saline-filled implants or TRAM flaps) and those who did not have
      reconstruction, both groups had increasing psychological distress, but the women
      who had reconstruction had slightly higher scores. Women with a history of
      psychiatric treatment showed the greatest increase in psychological symptoms.
      CONCLUSION: Breast implant removal did not have psychological benefits in this
      group of women. Breast reconstruction after removal did not appear to be
      psychologically beneficial to this cohort.

PMID- 9283556
TI  - Anatomical course of the lateral femoral cutaneous nerve and its susceptibility
      to compression and injury.
AB  - The anatomy of the lateral femoral cutaneous nerve was investigated through
      dissection of 52 human anatomic specimens. The variability of its course and
      locations as it exists the pelvis is described and related to soft-tissue and
      bony landmarks. Five different types are identified: type A, posterior to the
      anterior superior iliac spine, across the iliac crest (4 percent); type B,
      anterior to the anterior superior iliac spine and superficial to the origin of
      the sartorius muscle but within the substance of the inguinal ligament (27
      percent); type C, medial to the anterior superior iliac spine, ensheathed in the
      tendinous origin of the sartorius muscle (23 percent); type D, medial to the
      origin of the sartorius muscle located in an interval between the tendon of the
      sartorius muscle and thick fascia of the iliopsoas muscle deep to the inguinal
      ligament (26 percent); and type E, most medial and embedded in loose connective
      tissue, deep to the inguinal ligament, overlying the thin fascia of the iliopsoas
      muscle, and contributing the femoral branch of the genitofemoral nerve (20
      percent). The results of this study suggest that the lateral femoral cutaneous
      nerve is most susceptible to mechanical trauma when the nerve is type A, B, or C.

PMID- 9283557
TI  - Toe-to-hand transfer for traumatic digital amputations in children and
      adolescents.
AB  - In the period from July of 1990 to August of 1994, 45 toe or toe tissue transfers
      were performed in 28 children and adolescents with traumatic amputation of
      digits. The average age at the time of transfer was 12 years (range, 3 to 16
      years), and the median age was 10 years. The methods of reconstruction included
      transfer of 6 trimmed great toes, 2 great toe pulps, 24 second toes, 1
      vascularized metatarsophalangeal joint from the second toe, 2 third toes, 4
      combined second and third toes. and 1 combined third and fourth toes. All of the
      transferred toes, except one second toe, ultimately survived. Exploration and
      reanastomosis were required in three cases owing to arterial insufficiency.
      Partial pulp loss occurred in two digits. Follow-up ranged from 1 to 5 years
      (average, 3 years). Bony union occurred uneventfully in all patients. Two-point
      discrimination averaged 5 mm (static) and 6 mm (moving). Active range of the
      motion averaged 69, 38, and 13 degrees at the metaphalangeal proximal
      interphalangeal and distal interphalangeal joints of the reconstructed fingers,
      respectively, and 15 degrees at the interphalangeal joint of the reconstructed
      thumbs. None of the children required subsequent tenolysis. Pulp plasty was
      performed in nine digits in seven patients. Radiologically, the transferred
      phalanges showed the some growth as the non-transferred ones. Trimming the great
      toe before transfer did not result in premature physeal closure or growth
      retardation. The donor foot maintained a satisfactory appearance. None of the
      patients complained of difficulty in running or jumping. Toe-to-hand transfer in
      children, performed meticulously, can provide a valuable option for
      reconstruction of traumatic digit loss.

PMID- 9283558
TI  - Treatment of irreversible lesion of the radial nerve by tendon transfer:
      indication and long-term results of the Merle d'Aubigne procedure.
AB  - Irreversible radial nerve paralysis should be treated by tendon transfer
      reconstruction to improve wrist and finger extension and stabilization of the
      thumb joints. Many different techniques and modifications are known and used. A
      total of 43 patients, all of whom underwent the Merle d'Aubigne procedure, were
      examined in a long-term follow-up study. Short-term and long-term subjective and
      objective results were evaluated. The improvement of the motions between initial
      and follow-up examinations could be demonstrated. Thirty-eight patients were able
      to return to their former jobs. Interestingly, the majority of the patients were
      able to move their fingers separately. This finding could be proved by the
      electromyography and explained by the counteracting flexor tendons. The overall
      findings indicate that the Merle d'Aubigne procedure is an excellent and reliable
      tendon transfer method.

PMID- 9283559
TI  - Repeated bone repositioning in the growing rabbit calvarium hampers bone segment
      incorporation.
AB  - There has been concern among surgeons that multiple extended craniofacial
      procedures might be detrimental to the viability of the involved skeletal
      structures. This study aimed to explore the result of repeated bone
      repositionings in the growing rabbit calvaria. Seven immature rabbits were
      subjected to a three-stage surgical procedure, implying that four calvarial bone
      segments were originally harvested and repositioned according to a rotational
      scheme; after 6 weeks only three of the bone segments were harvested and
      repositioned and, finally, after an additional period of 6 weeks, two segments
      were repositioned. The results were evaluated by radiographic, histologic (with a
      special scoring system), and histomorphometric analysis. It was found that one or
      two cranioplasties did not markedly affect graft incorporation, but three
      procedures significantly reduced graft revascularization and integration. The
      findings are discussed with special reference to syndromic craniofacial
      disorders.

PMID- 9283560
TI  - Blood flow in mobilized nerves: results in a rabbit sciatic nerve model.
AB  - The purpose of this study was to evaluate the immediate effect on capillary blood
      flow of surgical mobilization of 15 cm of the rabbit sciatic and tibial nerve.
      Capillary nerve blood flow was determined with 16-micron radioactive
      microspheres. Thirty-seven rabbits were divided into six groups. In the control
      group A (n = 7), the in situ nerve blood flow was determined. In group B (n = 7),
      the nerve was mobilized, leaving only the proximal and distal endoneurial
      vascular supplies; blood flow increased compared with in situ values in most
      segments. In group C (n = 5), the nerve was mobilized as in group B, but also
      transected distally; blood flow was markedly decreased in the distal segments but
      was maintained up to a diameter-to-length ratio of 1:63. In group D (n = 6), the
      nerve was not mobilized, but was transected proximally and distally; blood flow
      increased in all segments. In group E (n = 5), the nerve was mobilized and
      transected proximally and distally, leaving only nerve branches intact; blood
      flow was significantly higher in segments of the nerve from which nerve branches
      originated with the nerve receiving blood flow through its branches. In group F
      (n = 6), the nerve was mobilized, all extrinsic vessels except one were
      transected, and the proximal and distal nerve was transected; flow was maintained
      to a diameter:length ratio of 1:41 from the source of blood flow. Therefore, it
      does appear that long lengths of nerve may be mobilized and transposed while
      maintaining sufficient blood flow.

PMID- 9283561
TI  - Transverse carpal ligament: its effect on flexor tendon excursion, morphologic
      changes of the carpal canal, and on pinch and grip strengths after open carpal
      tunnel release.
AB  - A three-part study is described that examines postoperative weakness after open
      carpal tunnel release and investigates the role of the transverse carpal ligament
      in the digital flexor pulley system. The effect of this ligament on flexor tendon
      excursion is evaluated in a cadaver study. Magnetic resonance imaging analysis is
      used to determine whether division of the transverse carpal ligament promotes
      volar migration of the median nerve and flexor tendons. Finally, the effects of
      ligament division and various methods of transverse carpal ligament
      reconstruction on the return of grip and pinch strengths after open carpal tunnel
      release are evaluated. The authors were able to determine that transverse carpal
      ligament reconstruction, particularly the transposition flap repair technique,
      after open carpal tunnel release confers a mechanical advantage and that the
      transverse carpal ligament is an important pulley for flexor tendon excursion.
      Based on the magnetic resonance imaging studies, volar displacement of carpal
      contents is reduced in patients undergoing transverse carpal ligament
      reconstruction by means of a transposition flap compared with those undergoing no
      ligament reconstruction and those undergoing reconstruction using the palmar
      aponeurosis. Postoperative grip and pinch strength values for the transposition
      flap repair group surpassed those of the other two groups at 12 weeks.

PMID- 9283562
TI  - Investigation of silicone oil and fumed silica in an adjuvant animal model.
AB  - Human adjuvant disease is the label given to a syndrome that resembles a
      connective tissue disease such as scleroderma and that has been hypothesized to
      follow augmentation mammoplasty with silicone gel implants or silicone with
      adulerants. To date, there is no proof that pure silicone is the cause of these
      symptoms. The cases presented in the literature suggest a comparison to the
      events seen in the rat adjuvant arthritis model. Male Lew/SsN rats (n = 65) were
      used. To evaluate both the adjuvant and antigenic properties of the gel implant,
      variations of the standard Freund's complete adjuvant inoculum were prepared.
      Tested were the abilities of low molecular weight silicone to act as an adjuvant
      and for fumed silica to act as an antigen by modifying a rat adjuvant arthritis
      model to include silicone and fumed silica. On day 0, 0.25 ml of each inoculum
      was injected intradermally into the plantar aspect of the hindfoot of each rat.
      The foot diameter was recorded at each time period, compared with the
      contralateral hindfoot, and normalized to controls at regular time periods over
      the course of 120 days. Silicone oil did not act as an adjuvant. Furthermore,
      fumed silica alone did not act as an antigen; however, it is capable of eliciting
      a reaction that is both delayed and uncharacteristic of the rat adjuvant
      arthritis model. These results indicate that "human adjuvant disease" may be
      inappropriate and misleading.

PMID- 9283563
TI  - Implementation of parameters in the expansion ratio of mesh skin grafts.
AB  - Expansion of a mesh skin graft depends on factors pertaining to the graft itself
      as well as on parameters of the meshing device. With regard to the graft, we
      examine the efficiency of graft handling and thickness of the skin graft. With
      regard to the parameters of the meshing apparatus, which determine the expansion
      ratio: (1) d equals the distance between the cutting blades, which will become
      the width of the mesh ribbons and is an underestimated parameter for expansion;
      and (2) L equals the length of cut, which determines proportionally the expansion
      ratio. This length defines the maximal distance of the raw square of the expanded
      mesh and therefore the healing time by epithelialization. The authors present a
      mathematical formula of expansion ratio that allows for an objective comparison
      of skin meshing apparatuses. It is concluded that optimal mesh skin grafting is
      based on mathematical principles rather than on inventive instrumentation.
      Furthermore, an analysis of the mechanical parameters as given by the
      manufacturers is important in anticipating healing time per expansion ratio.

PMID- 9283564
TI  - Growth factors in the repair of partial thickness porcine skin wounds.
AB  - In 28 porcine partial thickness excisional wounds, the presence of several growth
      factors was first studied by enzyme-linked immunoadsorbent assay on wound fluid
      collected in sealed wound chambers. Basic fibroblast growth factor (bFGF) peaked
      on day 1 at 31.4 pg/ml; platelet derived growth factor (PDGF)-AB on day 3 reached
      45.2 pg/ml, and transforming growth factor-beta (TGF-beta) on day 7 was 726.1
      pg/ml. The same chamber system was used in 48 partial thickness excisional wounds
      for delivery of nanogram doses of bFGF, PDGF-AB, insulin-like growth factor (IGF)
      1, epidermal growth factor (EGF), and cholera toxin. PDGF and EGF accelerated
      healing (1.1 days and 0.3 days, respectively), whereas bFGF and IGF-1 had no
      effect. Cholera toxin retarded healing by 1.9 days. Furthermore, in 100
      excisional wounds EGF in the concentration range of 10 to 1,000 ng/ml had the
      same stimulating effect on healing. EGF at 10,000 ng/ml significantly delayed
      healing. The wound chamber model is useful for detecting of endogenous growth
      factors as well as for delivering exogenous factors.

PMID- 9283565
TI  - Vascular delay in skeletal muscle: a model for microcirculatory studies.
AB  - Dynamic myoplasty is a relatively new use for muscle flaps and has led us to
      revisit the mechanisms of vascular delay as a means of optimizing blood supply to
      muscle flaps. Despite the well-documented effectiveness of vascular delay in skin
      flaps, vascular delay in muscle flaps has not been widely reported. Regardless of
      the many mechanisms postulated in the literature as contributors to the delay
      effect in skin, the one element common to all these hypotheses is the importance
      placed on changes in the microcirculation. Based on this factor, in the present
      study we developed and validated an animal model in which delay-induced
      microvascular changes could be measured in skeletal muscle flaps. We used the
      hairless mouse latissimus dorsi muscle flap because its vascular distribution is
      similar to that of humans and its thin structure will enable us in future studies
      to directly view and measure its microvasculature using videomicroscopy. In 12
      animals, we found that delay significantly (p < 0.01) reduced necrosis of the
      distal part of the muscle from 57 +/- 9 percent in nondelayed flaps (n = 7) to 22
      +/- 3 percent in delayed (n = 5) flaps. In these studies, we also determined that
      the hairless mouse latissimus dorsi muscle flap will serve as an excellent model
      for defining microvascular changes throughout delay.

PMID- 9283566
TI  - Role of nitric oxide in the regulation of osteoblast metabolism.
AB  - Nitric oxide has recently been shown to inhibit the proliferation of several
      types of cells, including osteoclasts. Both osteoclasts and osteoblasts have
      inducible nitric oxide synthase and produce nitric oxide. Although the direct
      effect of nitric oxide on osteoblasts in general and osteoblast proliferation in
      particular has not been delineated, the authors performed studies to clarify the
      role of nitric oxide on osteoblast proliferation and metabolism. Cultures of
      human osteoblasts were exposed to 0.1, 1.0, and 10 microM of the nitric oxide
      releasing agent 3-morpholino sydnonimine (SIN-1) for 7 days. Cells were evaluated
      for proliferation and production of alkaline phosphatase and osteocalcin.
      Osteoblasts exhibited decreased proliferation relative to control cultures at 1.0
      and 10 microM concentrations of SIN-1 (p < 0.05). Concentrations of 1.0 and 10
      microM of SIN-1 effected a decreased production of osteocalcin and alkaline
      phosphatase (p < 0.05). The results of these studies indicate that nitric oxide
      may play a critical role by which osteoblasts exhibit self-regulation of mineral
      metabolism.

PMID- 9283568
TI  - Supernumerary nostril in association with incomplete naso-ocular cleft.
AB  - Supernumerary nostril is an extremely rare congenital anomaly with sporadic
      reports of its occurrence in the literature. Associated congenital anomalies have
      not been present in the cases described. The treatment is excision of the
      nostril, using the technique of a fistulectomy, and associated procedures to
      correct a bifid nasal tip or wide columella base. We describe our experience with
      this anomaly in an adult male, who had features of an incomplete naso-ocular
      cleft. We treated it by excising the accessory nostril, repositioning the
      displaced alar base, and providing skin and lining, which were both deficient, by
      local flaps.

PMID- 9283567
TI  - Acute and chronic animal models for excessive dermal scarring: quantitative
      studies.
AB  - Excessive scarring in the form of keloids and hypertrophic scars continues to be
      a clinical problem for some patients. The lack of an animal model for such
      scarring has been an obstacle to studying the cellular and molecular biology of
      these entities. Previous observations made by the authors that some surgical
      scars in the rabbit ear remain raised for months after wounding prompted us to
      investigate whether the rabbit ear might provide a model by which to study
      excessive dermal scarring. After establishing the model in preliminary study, 40
      excisional wounds, 6 mm in diameter, were created over the ventral surface of
      rabbit ears. Elevated scars were treated with either intralesional triamcinolone
      acetonide or saline at day 16 postwounding. On day 22, 25 scar wounds were used
      for thorough histomorphometric analysis, 15 wounds were eliminated prior to
      analysis because of invagination of epithelial tissue, which made analysis
      difficult. Total area of scar and Hypertrophic Index, a ratio comparing scar
      prominence with the thickness of adjacent unwounded tissue, were measured for 25
      (62 percent) of the resulting scars. Both total area of scar and Hypertrophic
      Index were found to be significantly decreased in the steroid-treated group (p <
      0.02 and < 0.03, respectively). In a chronic form of this model, in which larger
      excisions were taken, an excessive accumulation of both new collagen and
      cartilage over 9 months was observed. An animal model for excessive dermal
      scarring that allows quantitation of scar formation and, at an early stage, can
      be modulated in a predictable way with intralesional corticosteroid treatment is
      presented. This model may parallel hypertrophic scarring in humans and thus might
      provide a tool by which to study its pathophysiology and objectively evaluate
      therapeutic modalities.

PMID- 9283569
TI  - Reconstruction of the localized eyebrow defect.
AB  - A localized eyebrow defect can be reconstructed with the double-Z rhombic
      technique. A previously unreported characteristic of this technique is its
      ability to maintain relative vertical alignment of anatomic landmarks as the
      defect is collapsed horizontally.

PMID- 9283570
TI  - Free latissimus dorsi myocutaneous flap for secondary breast reconstruction after
      partial loss of a TRAM flap.

PMID- 9283571
TI  - Bidirectional armed needle: a useful surgical tool in plastic surgery.
AB  - We propose the application of a bidirectional armed needle, which facilitates
      suturing and soft-tissue fixation. This device can be used during the "back-and
      forth" suturing method that is often used in centrofacial lift, nasolabial-fold
      correction, malar eminence suspension, submental platysmoplasty, canthopexy, etc.
      It is very useful for performing running mattress sutures and also for mini
      invasive and other sophisticated procedures. The advantages of this needle
      includes a shorter operating time and lower morbidity. It is a useful tool with
      multiple applications in plastic surgery.

PMID- 9283572
TI  - Anatomy of alar cartilages in blacks.
AB  - We conducted a morphologic and anatomic study on 24 alar cartilages in 12 Black
      American male cadavers. Measured parameters included the greatest height and
      width of each lateral crus and the distance of the caudal boarder of the lateral
      crus from the alar rim. The average height of the lateral crura was 1.2 cm and
      the average width was 1.8 cm. These measurements approximate those reported for
      Caucasians. They suggest that contrary to popular impression, the alar cartilages
      in Black Americans as a group may not be significantly smaller than in Caucasian
      Americans. The Black American alar cartilages in our study were found to be
      approximately the same distance from the nostril rim as those in the Caucasians.
      Three morphologic types of alar cartilages were found in our study. The most
      common shape was the convex-concave, found in 50%, followed by the smooth convex
      shape (33.3%). The simple-symmetrical and simple-interlocking (male-female)
      relationships of the medical crura were found in 50% and 41.7% of our specimens,
      respectively. There was one specimen of complex-interlocking (complex
      symmetrical) relationship. These findings were compared with those described in
      Caucasians. The variability in the width of the alar cartilages in our study was
      found to be consistent with our division of the Black American nose into three
      types: type A (African), type B (Afro-Caucasian) and type C (Afro-Indian). The
      clinical significance of the results is discussed.

PMID- 9283573
TI  - Fibrin glue fixation in forehead endoscopy: evaluation of our experience with 206
      cases.
AB  - The endoscopic approach has totally replaced the bicoronal approach for the
      treatment of forehead aging in our practice since November of 1993. The fixation
      in proper position is obtained with fibrin glue. Results of a series of 206
      procedures performed in 196 patients are presented. Eyebrow positioning and
      muscle weakening were rated on a scale of 1 to 4. The evaluation has been made at
      a minimal follow-up time of 6 months. The comparison of the results between the
      first series of 28 patients during the first 6 months of our experience and the
      second series of 69 patients during the following period showed a significant
      increase in the number of excellent results (from 47 to 78 percent). Altogether,
      the satisfactory results (rated excellent or good) increased from 71 to 86
      percent. Fibrin glue provides a stable fixation with the possibility of
      displacement in several directions, including transversal expansion.
      Complications have been minimal. Secondary procedures and association with other
      facial operations have been analyzed.

PMID- 9283574
TI  - Update: lifting the malar fat pad for correction of prominent nasolabial folds.
AB  - The malar fat pad suspension technique is a safe and effective method for
      rejuvenation of the aging midface. When combined with the SMAS-platysma rotation
      flap face-lift as a multi-vector technique, most of the changes that occur with
      aging are addressed and corrected in an anatomic fashion, resulting in an
      aesthetically pleasing result. Careful attention to the tension and position of
      the suspension suture enhances the improvement of the infraorbital flattening as
      well as correcting the excessive prominence of the nasolabial fold.

PMID- 9283575
TI  - Pseudoherniation of the buccal fat pad: a new clinical syndrome.
AB  - The differential diagnosis of cheek masses can include any component that arises
      from the region or that metastasizes to it. Given the array of potential
      anomalies that can present in this area and their clinical implications, an early
      diagnosis is essential. This report describes a condition observed in a series of
      patients with abnormal positioning of the buccal fat pad as the cause of their
      cheek masses. In the appropriate setting, a soft, nontender, walnut-sized mass
      that reduces into the buccal space is pathognomonic for the syndrome referred to
      as pseudoherniation of the buccal fat pad. Magnetic resonance imaging can also be
      used to evaluate the region. Treatment is accomplished by excision or repair of
      the fascial defect.

PMID- 9283576
TI  - Carcinogenic potential of silicone breast implants: a Connecticut statewide
      study.
AB  - To clarify the carcinogenic potential of silicone breast implants, 680 implant
      procedures performed on women in Connecticut with no prior history of cancer were
      correlated with the subsequent development of primary breast and nonbreast
      cancers. Neoplastic events after the placement of silicone breast implants during
      the 13-year interval from October 1, 1980, through September 30, 1993, were
      quantified using a retrospective, linked-registry method. ICD-9-CM discharge
      codes contained in the Uni formed Hospital Discharge Data Sets (UHDDS) from 34
      hospitals across Connecticut were linked to procedure codes for unilateral and
      bilateral implants, and to medical histories for new malignancies after the
      implant procedures. Data were cross-linked to the Connecticut Tumor Registry to
      confirm the clinical history of each cancer. The rates of breast and nonbreast
      cancers in patients with silicone breast implants were compared with those of a
      control population drawn from the UHDDS of 1022 women undergoing sterilization by
      tubal ligation between 1981 to 1985. Ages (mean +/- SD) were similar in the
      implant group (34 +/- 10 years) and in the sterilization group (32 +/- 6 years).
      The mean follow-up in the implant group (4.6 years) was also similar to that of
      the control group (5.4 years). Compared with the control group, the implant group
      demonstrated lower rates of breast cancer (0.59 versus 0.88 percent, p = 0.35)
      and nonbreast cancer (0.59 versus 2.7 percent, p = 0.001). Correspondingly, the
      implant group had a lower relative risk of breast cancer (relative risk = 0.67,
      95 percent, confidence interval = 0.20 to 2.17) and nonbreast cancer (relative
      risk = 0.21, 95 percent, confidence interval = 0.07 to 0.60). Based on these
      data, it was concluded that silicone breast implants are not carcinogenic,
      because they are not associated with increased rates of either breast or
      nonbreast cancers. The validity and threats to the conclusions are discussed, and
      the results are placed into context with similar findings from other studies.

PMID- 9283578
TI  - A simple technique to determine the future location of the umbilicus in
      abdominoplasty.
AB  - We present a new, simple technique for umbilical positioning in abdominoplasty.
      The technique is concluded to be a practical one, especially for staff in
      training.

PMID- 9283577
TI  - Subacute torsion of periprosthetic capsular tissue presenting as a painful breast
      tumor.

PMID- 9283579
TI  - Endoscopically assisted supraorbital nerve neurolysis and correction of eyebrow
      asymmetry.

PMID- 9283580
TI  - The future of plastic surgery in academic medical centers: making the case for
      autonomous departments of plastic surgery.

PMID- 9283582
TI  - Total nose reconstruction--the Converse-Galvao flap.

PMID- 9283581
TI  - History of the American Society of Maxillofacial Surgeons: 1947-1997.

PMID- 9283583
TI  - The necessity for aggressive treatment with Marjolin's ulcers of the scalp.

PMID- 9283584
TI  - The Malaga flap for vaginoplasty in the Mayer-Rokitansky-Kuster-Hauser syndrome:
      experience and early-term results.

PMID- 9283585
TI  - Arteriovenous shunts for hemodialysis: a useful clinical progression from the
      microsurgical laboratory.

PMID- 9283586
TI  - DNA hypomethylation in breast cancer: an independent parameter of tumor
      progression?
AB  - The global DNA methylation status was investigated on a series of 59 breast
      cancers by Southern blotting, using methylation sensitive restriction enzymes. By
      comparison to control DNA, almost all tumor DNAs were found globally
      hypomethylated. However, the demethylation was variable from tumor to tumor.
      Compared to other biological parameters, the methylation did not correlate with
      chromosome alterations, steroid hormone receptor status, or histopathological
      grading. Tumors which appeared to be the most evolved for other parameters were
      only mildly hypomethylated, whereas tumors with strongly hypomethylated DNA
      corresponded to those with slight alterations of the other parameters. Thus, DNA
      hypomethylation is a consistent characteristic of breast cancer, but its
      variations may not correlate with tumor progression of most breast cancers.

PMID- 9283587
TI  - A translocation between 3q21 and 12q24 in a patient with minimally differentiated
      acute myeloid leukemia (AML-M0).
AB  - Only a small number of reports have described the cytogenetic analysis of
      minimally differentiated acute myeloid leukemia (AML, M0). We performed a
      cytogenetic analysis on a patient with AML (M0) with a normal platelet count. It
      revealed a chromosomal translocation between chromosome bands 3q21 and 12q24. 3q.
      Abnormalities in AML are known to be associated with normal or elevated platelet
      counts. 3q21 and 12q24 are common translocation sites in AML patients, but this
      is the first report of translocation t(3;12)(q21;q24) in an AML patient.

PMID- 9283588
TI  - Double minute chromosomes and myelodysplastic syndrome: a case report and
      literature review.
AB  - Double minute chromosomes (dmin) occur in about 3.3-10.6% of acute leukemia,
      especially in the elderly. However, dmins are relatively rare in myelodysplastic
      syndrome (MDS). We describe a case of refractory anemia with excess blasts
      associated with complex cytogenetic abnormalities, dmins, and brief survival.

PMID- 9283589
TI  - Monoallelic p53 deletion in chronic lymphocytic leukemia detected by interphase
      cytogenetics.
AB  - Chromosomal aberrations can be detected in 50% of patients with chronic
      lymphocytic leukemia (CLL). A role for tumor suppressor genes in the genesis of
      lymphoid tumors has been reported. In B-CLL, p53 gene mutations were found in 10
      15% of the patients. We used fluorescence in situ hybridization (FISH) to detect
      p53 deletion in B-CLL. We also correlated the cytogenetic findings with the
      clinical course. In situ hybridization to interphase nuclei showed monallelic p53
      deletion in 6 of 23 patients (26%). The percentage of cells with one p53 signal
      ranged from 12 to 100. A statistically significant correlation between p53
      deletion and progression of CLL was demonstrated. We conclude that FISH is a
      sensitive and reliable method to detect deletion of specific genes (i.e., p53) in
      CLL. The finding of p53 deletion is associated with disease progression.

PMID- 9283590
TI  - Fluorescence in situ hybridization assessment of chromosome 8 copy number in
      stage I and stage II infiltrating ductal carcinoma of the breast.
AB  - A total of 34 cases of infiltrating ductal carcinoma of the breast, not otherwise
      specified (NOS), were selected, based on the clinical stage of the disease (17
      cases stage I and 17 cases stage II). The histologic grade and the DNA content of
      each tumor were evaluated. Each specimen was analyzed and blinded cytogenetically
      for the frequency of chromosome 8 copy number using fluorescence in situ
      hybridization (FISH). Among the informative samples, 16 cases were disomic (47%)
      and 18 cases (53%) were trisomic. Of the 16 disomic tumors, 13 cases (81%) were
      classified clinically as stage I disease and 3 cases (19%) were stage II disease.
      Of the 18 trisomic tumors, 4 cases (22%) were stage I, and 14 cases (78%) were
      stage II. Microscopically, all trisomic tumors were of high histologic grade and
      aneuploid when analyzed by flow cytometry. We inferred from these data that a
      subset of infiltrating ductal carcinomas (NOS) is characterized by chromosome 8
      trisomy. This chromosomal abnormality correlates well with other markers that
      predicate aggressive biological behavior of the tumor. While this observation
      needs to be further extended, the data suggest that chromosome 8 copy number may
      be used as a possible marker to identify a subgroup of patients with infiltrating
      ductal carcinoma associated with a poor prognosis.

PMID- 9283591
TI  - Increased spontaneous formation of micronuclei in cultured fibroblasts of first
      degree relatives of familial melanoma patients.
AB  - The phenomenon of spontaneous increased micronuclei and enhanced UV-sensitivity,
      which is known for familial cutaneous malignant melanoma (CMM) patients, could be
      demonstrated again in fibroblasts of 17 familial CMM patients. In order to
      determine if close relatives of familial CMM patients show both a comparable
      spontaneous chromosomal instability and enhanced UV-sensitivity, cultured
      fibroblasts of 24 healthy, first-degree relatives of patients with familial
      malignant melanoma were investigated. The cytokinesis-block micronucleous
      technique was used to detect enhanced chromosomal instability. Fibroblasts of the
      investigated relatives showed a significantly increased spontaneous formation of
      micronuclei, in comparison to 19 healthy controls, but no enhanced UV-sensitivity
      was evident. We conclude that chromosomal instability might be a hereditary trait
      and a causative factor in developing familial malignant melanoma. This supports
      the concept of a genetic predisposition to familial CMM and may help to identify
      high-risk family members at a cytogenetic level in addition to the common
      clinicopathological traits.

PMID- 9283592
TI  - Klinefelter syndrome and non-Hodgkin lymphoma.
AB  - Patients with a 47,XXY karyotype (Klinefelter syndrome) appear to have an
      increased risk of developing cancer, especially male breast cancer and germ cell
      tumors, but rarely malignant hematologic disorders. We report a patient with a
      low grade B-cell non-Hodgkin lymphoma with a 47,XXY karyotype in both the tumor
      and constitutional cells. This is only the 13th reported case of malignant
      lymphoma in a patient with Klinefelter syndrome. Although some authors postulate
      that the 47,XXY karyotype may be a predisposing factor in the development of
      hematological malignancies, the lack of reported cases suggests that such
      associations may be no more than chance findings.

PMID- 9283594
TI  - A subgroup of breast carcinomas is cytogenetically characterized by trisomy 12.
AB  - Chromosome analysis of short-term cultured breast carcinoma cells revealed
      trisomy 12 in four cases. In one tumor it was the only abnormality. The second
      case showed cytogenetic polyclonality, but the mainline had +12 as the sole
      change. In the remaining two tumors, trisomy 12 was part of more complex
      karyotypes. These findings, especially when coupled with similar information on
      previously published cases, show that gain of chromosome 12 is a recurrent and
      sometimes early event in breast carcinogenesis.

PMID- 9283593
TI  - High incidence of BCL-6 gene rearrangement in diffuse large B-cell lymphoma of
      primary gastric origin.
AB  - The incidence of BCL-6 gene rearrangement was studied in 39 Hong Kong Chinese
      patients with diffuse large B-cell lymphoma. The primary site of involvement was
      nodal in 18 cases and gastric in 21 cases. Clonal BCL-6 gene rearrangement was
      found in 17% of the patients with primary nodal and 48% with primary gastric
      lymphoma (p = 0.05). The clinical characteristics and treatment outcome of the 21
      patients with primary gastric lymphoma were analyzed according to the BCL-6
      status. Significantly more patients in the germline BCL-6 gene group had advanced
      stage (II, III and IV) of disease. Complete remission rate following primary
      therapy appeared to be higher for the positive rearrangement group (70% versus
      36%), but it was not statistically significant. Those with a rearranged BCL-6
      gene also appeared to have better survival at 5 years (58% versus 36%) but the
      difference was also not statistically significant. On the other hand, patients
      being classified as low risk according to the International Prognostic Index had
      significantly better survival at 5 years (89% versus 9%, p = 0.0001). We
      concluded that BCL-6 gene rearrangement was more commonly found in diffuse large
      B-cell lymphoma of primary gastric origin than its nodal counterpart and it may
      be playing a more important role in the pathogenesis of gastric large B-cell
      lymphoma. There was a trend that the BCL-6 gene rearrangement was associated with
      a more favorable outcome in patients with gastric large B-cell lymphoma but the
      difference was not statistically significant.

PMID- 9283595
TI  - Deletion of the long arm of chromosome 7 in myelomonocytic leukemia with bone
      marrow eosinophilia.
AB  - We report a 62-year-old man with acute myelomonocytic leukemia with bone marrow
      eosinophilia (M4Eo), and a deletion of the long arm of chromosome 7. The patient
      presented with pancytopenia, which shortly after evolved to overt leukemia. There
      was no response to the daunorubicin-cytosine arabinoside (Ara-C) regimen, and a
      remission achieved with amsacrine (AMSA)-Ara-C lasted only for a short time. On
      relapse, a peculiar skin rash accompanied the hematologic picture. While ANLL
      with chromosome 7 abnormalities usually carries adverse prognosis, patients with
      M4Eo (which is usually associated with chromosome 16 abnormalities) do better.
      The patient described here examplifies that M4Eo may be associated with
      del(7)(q22), and that it is the chromosomal abnormality rather than the type of
      leukemia that might determine the clinical outcome.

PMID- 9283596
TI  - Chromosomal characteristics of childhood brain tumors.
AB  - In the present cytogenetic analysis of 116 pediatric brain tumors, chromosomal
      abnormalities were demonstrated in 44 cases, 48 cases revealed only 46,XX or
      46,XY cells, and 24 cases were nonproductive. In contrast to studies of adult
      brain tumors in which isolated loss of one X or the Y chromosome is often
      encountered, 45,X,-X and 45,X-Y stemlines or sidelines were not observed in this
      series of childhood tumors. Among the 17 medulloblastomas with cytogenetic
      abnormalities, chromosome 1 was most frequently affected by structural
      deviations; the most prevalent specific alteration (7 of 17 tumors) was loss of
      17p, through i(17)(q10) or unbalanced translocation. The majority of low grade
      astrocytomas had normal stemlines, although one pilocytic astrocytoma and one
      cerebellar astrocytoma had frequent telomeric associations and a second pilocytic
      astrocytoma had a clone with trisomy 11. Thirteen of 19 high-grade and recurrent
      astrocytic tumors had abnormal stemlines that were approximately equally divided
      among cases with chromosomal counts in the near-diploid, hyperdiploid, and near
      triploid-tetraploid ranges. Although no consistent abnormalities were observed,
      subsets of cases had structural abnormalities of chromosome 3, 7q, 9q, or 17p.
      The cases of childhood brain tumors described here demonstrate that 45,X,-X, and
      45,X,-Y stemlines or sidelines are rare in these tumors and confirm frequent loss
      of 17p in medulloblastomas. High-grade astrocytic tumors in children frequently
      have abnormal stemlines, often in the hyperdiploid and polyploid ranges, and they
      differ from high-grade gliomas in the adult by lacking consistent numerical and
      structural deviations.

PMID- 9283597
TI  - Comparative genomic hybridization analysis of human neuroblastomas: detection of
      distal 1p deletions and further molecular genetic characterization of
      neuroblastoma cell lines.
AB  - Deletions of the short arm of chromosome 1 and MYCN amplification are the most
      frequently encountered genetic changes in disseminated neuroblastomas and
      neuroblastoma cell lines. Different strategies have been followed for detection
      of these and other genomic changes in neuroblastoma including karyotyping, FISH,
      and LOH, each with its own limitations. Here we report upon the evaluation of
      comparative genomic hybridization (CGH) in the analysis of neuroblastoma cell
      lines, with the emphasis on the assessment of the reliability of CGH for the
      detection of distal 1p deletions. We have analyzed seven neuroblastoma cell lines
      for which the 1p status was previously studied in detail using FISH and LOH. Our
      results show that CGH allows reliable detection of distal 1p deletions, including
      a small interstitial deletion in cell line SK-N-AS. Furthermore, CGH also allows
      the detection of chromosomal imbalance which would otherwise remain undetected,
      and provides useful information for further molecular characterization of
      chromosomal imbalances.

PMID- 9283598
TI  - Proliferative genes induce somatic pairing defects in Drosophila melanogaster and
      allow replication.
AB  - Drosophila tumor forming lines (malignant brain tumor, lethal giant larvae, discs
      large, brain tumor, and tumor suppressor gene) exhibit incomplete somatic pairing
      of specific regions in the salivary gland chromosomes, indicating that excessive
      cell proliferation correlates with somatic pairing defects in Drosophila. Alleles
      of malignant brain tumor enhancing the frequency of cell divisions exhibit
      melanizing tumors in the larvae. The giant chromosomes are defective in somatic
      pairing, indicating that a functional component of the chromosomes is influenced.
      Genes at different sites are affected, but the similarity of the phenotypes and
      complex complementation pattern reveals that their functions are interrelated. In
      the brain of malignant brain tumor recombinants and mutants in proliferative
      genes, polytene cells appear; wildtype does not amplify DNA in brain tissue
      cells. Thus, mutant proliferative genes induce the S-phase and allow replication
      of DNA.

PMID- 9283600
TI  - Identification of pericentric inversion 12, inv(12)(p13.1q11), by fluorescence in
      situ hybridization in a patient with acute myeloid leukemia (AML-M6).
AB  - Using probes located between 12p12.1 and 12p13.3, we performed fluorescence in
      situ hybridization (FISH) analysis and identified an inv(12)(p13.1q11) in a
      patient with acute myeloid leukemia (AML-M6). Standard cytogenetic analysis had
      identified the rearranged chromosomes 12 as del(12) (p11p13). Although deletions
      and translocations involving band 12p13 are fairly common chromosomal
      abnormalities observed in a broad spectrum of hematologic malignancies, inv(12)
      is a rather rare abnormality. We compare the clinical and cytogenetic findings
      with those of the previous cases reported in the literature.

PMID- 9283599
TI  - Isochromosome 14q in refractory anemia.
AB  - Trisomy 14 in hematologic disease is a rare finding and is almost exclusively
      associated with myeloid cell lineage. We present a case of refractory anemia (MDS
      RA) with the uncommon features of marked elliptocytosis and schistocytosis in the
      peripheral blood and isochromosome 14q. The analysis of the clinical outcome of
      this case and of others of myelodysplastic (MDS)/myeloproliferative syndromes
      with trisomy 14 as the sole abnormality suggests that it does not confer an
      unfavorable prognosis.

PMID- 9283602
TI  - Anomalies of chromosomes 17 and 22 in giant cell fibroblastoma.

PMID- 9283601
TI  - High frequency of trisomy 8 in acute promyelocytic leukemia: a fluorescence in
      situ hybridization study.
AB  - Correct diagnosis of acute promyelocytic leukemia (APL) requires proof of the
      translocation (15;17)(q24;q11), which appears to be absolutely specific for this
      particular type of myeloid disorder. We studied the karyotypes of 29 consecutive
      APL patients at diagnosis: in 5 of them banding techniques failed to detect the
      t(15;17). In these seemingly cytogenetically negative cases, fluorescence in situ
      hybridization (FISH) with a chromosome 17 painting probe detected a high
      percentage of mitoses with 3 hybridization signals: one derived from the intact
      chromosome 17, and 2 from the rearranged chromosomes 15 and 17. Trisomy 8 (+8) as
      a secondary chromosomal abnormality was observed in 8 cases (27.5%), confirming
      that the t(15;17) favors the acquisition of an extra chromosome 8. One of these 8
      cases showed a marker that was interpreted by FISH analysis as der(8) with
      duplication of a segment of the long arm carrying the c-MYC allele. Clinical
      features of patients with t(15;17) and +8 were no different from patients with
      t(15;17) alone. The usefulness of FISH to standard banding techniques in the
      detection of specific structural and/or numerical chromosomal abnormalities is
      confirmed in this report.

PMID- 9283604
TI  - Wilms tumor: summary of 54 cytogenetic analyses.

PMID- 9283603
TI  - Acute lymphoblastic leukemia with a novel t(3;12)(p25;q13)

PMID- 9283605
TI  - Localization of BRCA1 gene expression in adult cynomolgus monkey tissues.
AB  - The breast and ovarian cancer susceptibility gene BRCA1 encodes a phosphoprotein
      of 1863 amino acids containing a highly conserved N-terminal RING finger domain
      and a C-terminal acidic region typical of several transcription factors. BRCA1
      acts as a tumor suppressor that may inhibit the proliferation of breast and
      ovarian cancer cells. To gain knowledge and to further understand the biological
      function of BRCA1, we examined its localization and expression in various tissues
      from 20-year-old male and female cynomolgus monkeys (Macaca fascicularis) by in
      situ hybridization using a 35S-labeled human BRCA1 DNA probe fragment derived
      from exon 11. In mammary glands, BRCA1 expression was primarily located in the
      duct and acinar epithelial cells. In the ovary, strong BRCA1 expression was
      detected in granulosa cells in maturing follicles and in luteal cells of the
      corpus luteum, as well as in the epithelial cells overlying the tunica albuginea.
      Specific signal was also observed in epithelial cells of the oviduct,
      endometrium, cervix, and vagina. Moreover, BRCA1 was strongly expressed in the
      germinal epithelium of the seminiferous tubules as well as over interstitial
      cells of the testis, in the epithelium of the epididymis, and in epithelial cells
      bordering the glandular lumen of the seminal vesicles. Signal was also detected
      in both the anterior and posterior lobes of the pituitary. In the adrenal glands,
      the signal was greater in the zona glomerulosa compared to the two other cortical
      zones, whereas the medullary cells were weakly labeled. In the stomach, and in
      small and large intestine, epithelial cells of the crypts usually exhibited
      stronger positive reaction than that observed over surface epithelial lining
      cells. BRCA1 expression was also found in diverse types of epithelial cells of
      the thyroid, pancreas, salivary glands, trachea, urinary bladder, and kidneys. In
      addition to demonstrating widespread tissue- and cell-specific expression of the
      BRCA1 gene in primate tissues, primarily in the epithelia, we observed a weaker
      but specific signal in various other cell types, suggesting a generalized
      biological function of BRCA1.

PMID- 9283606
TI  - Pre-osteoblastic proliferation assessed with BrdU in undecalcified, Epon-embedded
      adult rat trabecular bone.
AB  - We evaluated bromodeoxyuridine (BrdU) immunohistochemistry in undecalcified adult
      rat tibiae to study cell kinetics in various bone compartments: primary and
      secondary spongiosae, periosteum, and bone marrow. Several regimens of BrdU
      administration were tested (i.p. injections and osmotic minipumps). We compared
      LR White resin, methylmethacrylate, and Epon-araldite embedding, microwave
      irradiation for antigen retrieval, several concentrations of sodium ethoxide for
      deplastification, and various DNA denaturation procedures. Paraffin-embedded
      decalcified tibiae and Epon-embedded bowel were used as positive controls. The
      best results were obtained in rats labeled with 40 mg of BrdU for 72 hr using
      osmotic minipumps. The procedure using a Microprobe system in Eponembedded bone
      tissue with a sodium ethoxide concentration of 50% for two intervals of 20 min
      provided the best staining quality and tissue preservation. Labeled pre
      osteoblastic cells and bone marrow cells could be counted. Epon embedding allowed
      preservation of tetracycline double labeling performed 1 to 5 days before
      sacrifice. The number of labeled pre-osteoblastic cells was correlated with the
      double-labeled surface area measured histomorphometrically.

PMID- 9283607
TI  - Crosslinked plasmalemmal cholesterol is sequestered to caveolae: analysis with a
      new cytochemical probe.
AB  - [symbol: see text]-Toxin (perfringolysin O), a cholesterol-binding toxin, was
      partially proteolyzed and biotinylated (BC theta) to eliminate hemolyzing
      activity and was used as a cytochemical probe. In fixed cells, binding of BC
      theta was intense in the plasma membrane, especially at the base of apical
      microvilli and in lateral processes. The labeling was abolished by pretreatment
      with filipin, digitonin, or tomatin. When living cultured cells were treated with
      BC theta and then with either fluorescein-avidin D or colloidal gold
      streptavidin, the labeling in fine dots was distributed on the cell surface
      without local concentration as long as cells were kept on ice. When the
      temperature was raised to 37 C after treatment, the probe formed discrete large
      patches and became sequestered to caveolae. Binding of BC theta alone without the
      secondary reagents did not cause redistribution even at 37 C. Because the plasma
      membrane maintains integrity even after binding of BC theta, the probe can be
      used not only for cytochemical labelling of fixed cells but for pursuing the
      behavior of crosslinked cholesterol molecules in living cells. By use of this new
      probe, the present study revealed that crosslinked cholesterol in the plasma
      membrane is sequestered to caveolae.

PMID- 9283608
TI  - In vivo modulation of connexins 43 and 26 of human epidermis by topical retinoic
      acid treatment.
AB  - After 14 weeks of topical application of 0.1% all-trans-retinoic acid to the
      napes of volunteers, we observed a 2.5-fold increase in the thickness of
      epidermis, owing to an increase (p < 0.001) in the number and size of
      keratinocytes and the induction of keratin 6. These changes in the
      differentiation of epidermal keratinocytes were paralleled by an increase in the
      amount of Cx43, a connexin that is normally expressed in human epidermis, and by
      the massive induction of Cx26, which is barely detectable in normal
      interfollicular epidermis, as judged at both the transcript (Northern blotting)
      and the protein level (immunolabeling). In contrast, retinoic acid treatment did
      not alter the morphology and connexin pattern of hair follicles or of sebaceous
      and sweat glands, and did not induce the expression of other connexins (C32,
      Cx37, Cx40) in either skin adnexae or epidermis. These observations suggest that
      the expression of two distinct connexins by interfollicular keratinocytes is
      related to selective changes in the differentiation program of epidermis that are
      induced by retinoic acid.

PMID- 9283609
TI  - In situ measurement of glutamate concentrations in the periportal, intermediate,
      and pericentral zones of rat liver.
AB  - We developed a quantitative histochemical assay for measurement of local
      glutamate concentrations in cryostat sections of rat liver. Deamination of
      glutamate by glutamate dehydrogenase (GDH) was coupled to the production of
      formazan and formazan precipitation was used for colorimetric visualization. The
      method was tested and validated with gelatin model sections with known glutamate
      concentrations. Calibration graphs showed linear relationships with high
      correlation coefficients (> 96%) between glutamate concentrations or section
      thickness and absorbance values. The method was reproducible, with a constant
      percentage of 60 +/- 5% of glutamate being converted in gelatin model sections
      containing glutamate concentrations of 2 mM and higher. Glutamate concentrations
      were estimated in periportal, intermediate, and pericentral zones of liver
      lobules that contain low, intermediate, and high GDH activity, respectively. In
      fed adult male rat livers, periportal zones contained the highest concentrations
      of glutamate (approximately 14 mM) and intermediate and pericentral zones
      approximately 13 and 9 mM, respectively. On starvation, glutamate concentrations
      increased only in the small rim of pericentral cells that express glutamine
      synthetase, to approximately 15 mM. In livers of fetal and newborn rats,
      glutamate was homogeneously distributed, with a concentration of approximately 5
      mM. In suckling rat liver, distribution of glutamate was still homogeneous but
      the concentration was increased to approximately 8 mM. These glutamate
      distribution patterns were in agreement with those detected
      immunohistochemically.

PMID- 9283611
TI  - Cellular distribution of the angiogenic factor heparin affin regulatory peptide
      (HARP) mRNA and protein in the human mammary gland.
AB  - The heparin affin regulatory peptide (HARP) growth factor, also known as
      pleiotrophin, is a developmentally regulated protein that displays biological
      functions during cell growth and differentiation. To study the physiological role
      of this protein, we investigated the cellular distribution of HARP mRNA and
      protein in the resting human mammary gland. In situ hybridization histochemistry
      revealed that HARP mRNA was localized in alveolar myoepithelial cells, whereas
      alveolar epithelial cells were negative. In the stroma, HARP mRNA was localized
      in endothelial cells and smooth muscle cells of blood vessels. Interestingly,
      HARP protein and mRNA were not always co-localized. HARP protein
      immunocytochemistry staining was observed in an area including both alveolar
      myoepithelial and epithelial cells, although epithelial cells do not express HARP
      transcript. In contrast, the distribution of HARP protein is parallel to that of
      HARP mRNA in endothelial and vascular smooth muscle cells. In the light of these
      results, the putative role of HARP in controlling the proliferation and/or
      differentiation of the different mammary cell types is proposed and discussed.

PMID- 9283612
TI  - ICAM-1/LFA-1 expression in acute osteodestructive joint lesions in collagen
      induced arthritis in rats.
AB  - Collagen-induced arthritis in rats is a widely used model of rheumatoid arthritis
      (RA). However, the joint immunohistopathology is less well characterized. The
      objective of this study was therefore to analyze whole ankle joints for markers
      known to mediate inflammatory mechanisms in RA. Indirect immunohistochemistry was
      performed on undecalcified cryostat sections for intercellular adhesion molecule
      1 (ICAM-1, clone 1A 29) and leukocyte function-associated antigen-1 (LFA-1, clone
      WT.1) expression, for CD4+ lymphocytes (clone W3/25), B-cells (clone HIS 14), and
      macrophages (clone ED2). Acute, osteodestructive arthritis (n = 8) induced with
      bovine collagen Type II was verified by clinical and radiological measures. LFA-1
      expression was found almost exclusively at sites associated with cartilage
      erosion or osteodestruction. ICAM-1 was similarly expressed in the vicinity of
      tissue degradation but also by blood vessels in peripheral areas of joint
      swelling. CD4+ lymphocytes and macrophages were more ubiquitous. B-cells were
      infrequent. In control animals (n = 4) ICAM-1 was expressed by synovial blood
      vessels. Macrophages were identified at the synovial lining. The results suggest
      that LFA-1 and ICAM-1 mediate important inflammatory events in this model.
      Similar findings in human RA synovium provide further arguments that collagen
      induced arthritis in rats might be regarded as a comparable disease.

PMID- 9283610
TI  - Peptide expression in GABAergic neurons in rat suprachiasmatic nucleus in
      comparison with other forebrain structures: a double labeling in situ
      hybridization study.
AB  - We investigated the characteristics of GABAergic neurons in the rat
      suprachiasmatic nucleus (SCN) in normal untreated rats by examination of co
      expressed peptides. We adopted double labeling in situ hybridization using a
      digoxigenin-labeled glutamic acid decarboxylase (GAD) riboprobe and 35S-labeled
      peptide riboprobes. GAD mRNA-positive neurons were distributed throughout the SCN
      from the rostal to the caudal pole. In the dorsomedial part of the SCN, most GAD
      mRNA-positive neurons co-expressed arginine vasopressin mRNA. In the
      ventrolateral part of the SCN, about two thirds of GAD mRNA-positive neurons co
      expressed vasoactive intestinal peptide (VIP) mRNA. Co-expression of GAD and
      somatostatin mRNA was observed in virtually all neurons of the intermediate part
      of the SCN. In contrast, these peptidergic traits were poorly expressed in
      hypothalamic GABAergic neurons outside the SCN. Vasopressin mRNA-positive cells
      in the supraoptic nucleus did not express GAD mRNA, and co-expression of
      somatostatin mRNA and GAD mRNA was rare in the periventricular hypothalamic
      nucleus. Similarly, the VIP mRNA co-expression ratio of GABAergic neurons in the
      cerebral cortex was far lower than that in the SCN.

PMID- 9283613
TI  - Characterization of acidic vesicles in multidrug-resistant and sensitive cancer
      cells by acridine orange staining and confocal microspectrofluorometry.
AB  - To study the pH gradient status through membranes of acidic vesicles, either in
      sensitive or in multidrug-resistant living cancer cells, we monitored the
      fluorescence-emission spectra of acridine orange. Successive stainings with a pH
      sensitive dye and AO showed that low-pH organelles were stained red by AO. In
      these compartments, high AO concentrations are driven by the pH gradient through
      membrane vesicles. The resulting rise in the dye's oligomeric/monomeric ratio
      induced an increase in the red/green (655-nm/530-nm) emission intensity ratio.
      Therefore, the accumulation of AO in acidic organelles was appraised by
      determination of the contribution of the red emission intensity (R%) in each
      emission spectrum, using laser scanning confocal microspectrofluorometry. In
      vesicles of multidrug-resistant K562-R cells, R% is significantly higher (72 +/-
      10%) than the value (48 +/- 8%) from K562-sensitive cells (p < 0.001). This
      result is interpreted as a more important accumulation of AO in acidic
      cytoplasmic structures of resistant cells, which induces a shift from AO monomers
      (green emission) to self-associated structures (red emission). Equilibration of
      the pH gradient through acidic organelles was performed by addition of weak bases
      and carboxylic ionophores. Ammonium chloride (0.1 mM), methylamine (0.1 mM),
      monensine (10 microM), or nigericine (0.3 microM) all suppressed the initial
      difference of local AO accumulation between both cell lines. These agents
      decreased the red emission intensity for the resistant cell line but not for the
      sensitive one. The same effects were induced by 50 microM verapamil, a
      pleiotropic drug-resistance modulator. Our data allow the hypothesis of a higher
      pH gradient through membranes of acidic organelles, which would be a potential
      mechanism of multidrug resistance via the sequestration of weak bases inside
      these organelles.

PMID- 9283615
TI  - Platinum porphyrins as phosphorescent label for time-resolved microscopy.
AB  - We investigated phosphorescent metalloporphyrins as potential labels for time
      resolved microscopy. On the basis of spectroscopic analysis of their
      physicochemical properties (quantum yield, molar absorption coefficient, decay
      times) the best candidates were selected. Next, we synthesized antibody and
      avidin metalloporphyrin conjugates. The optimal F/P ratio with respect to quantum
      yield, decay time, and retention of biological activity of these immunoreagents
      was determined. The reagents were then evaluated by in situ hybridization and
      immunocytochemical procedures for demonstration of hapten-labeled DNA probes,
      membrane antigens (CD type), and 28S rRNA. All stained samples exhibited bright
      phosphorescence that could be selectively detected using time-resolved
      microscopy, especially when glucose/glucose oxidase was added to the embedding
      medium to deplete oxygen. Applications of time-resolved detection of
      phosphorescent porphyrins in strongly autofluorescent material (histological
      sections) are discussed.

PMID- 9283614
TI  - Expression of RESP18 in peptidergic and catecholaminergic neurons.
AB  - We examined the expression of regulated endocrine-specific protein of 18-kD
      (RESP18) in selected peptidergic and catecholaminergic neurons of adult rat
      brain. In the hypothalamic paraventricular, supraoptic, and accessory nuclei,
      RESP18 mRNA was highly expressed in neurons immunostained for oxytocin and
      vasopressin. RESP18 mRNA was also highly expressed in paraventricular nucleus
      neurons immunostained for corticotropin-releasing hormone, thyrotropin-releasing
      hormone, and somatostatin. RESP18 mRNA was expressed in POMC cells of the arcuate
      nucleus, in neuropeptide Y cells of the dorsal tegmental nucleus, lateral
      reticular nucleus, and hippocampus, and in brainstem catecholaminergic neurons.
      RESP18 mRNA expression was high in all paraventricular and arcuate neurons, but
      RESP18 protein was detectable in the perikarya of a subset of these neurons,
      suggesting an important post-transcriptional component to the regulation of
      RESP18 expression. RESP18 antisera immunostained perikarya but not axon fibers or
      terminals. Sub-cellular fractionation of homogenates of several hypothalamic
      nuclei identified RESP18 protein in fractions enriched in endoplasmic reticulum.
      The presence of 22- and 24-kD RESP18 isoforms in the neural lobe of the pituitary
      indicated that some RESP18 protein exited the endoplasmic reticulum. The post
      transcriptional regulation of RESP18 expression and localization of RESP18
      protein primarily to the endoplasmic reticulum suggests that RESP18 plays a
      regulatory role in peptidergic neurons.

PMID- 9283616
TI  - Murine thymic nurse cells and rosettes: analysis of adhesion molecule expression
      using confocal microscopy and a simplified enrichment method.
AB  - Thymic nurse cells (TNC) and T-cell stromal rosettes (ROS) are two in vivo models
      for stromal cell-thymocyte interactions. We describe a simplified enrichment
      method for TNC and ROS that overcomes the necessity for large amounts of tissue.
      The complexes were further analyzed with confocal microscopy, and three subunits
      of ROS were defined on the basis of their central cell phenotype, i.e.,
      macrophage, dendritic, or epithelial cell rosettes. Because adhesion molecules
      are proposed to play a crucial role in T-cell development, we investigated CD44,
      LFA-1, and ICAM-1 expression in such complexes. The epithelial component of TNC
      expresses CD44 and ICAM-1, whereas intra-TNC thymocytes are LFA-negative. With
      regard to ROS, all subsets expressed CD44, and macrophage and dendritic cell ROS
      were also ICAM-1-positive and LFA-1-positive. The current protocol opens the
      possibility for further in vivo analysis of stromal cell-thymocyte interactions,
      e.g., for studies of scarce gene mutant mice.

PMID- 9283618
TI  - Detection of the receptor for the human urokinase-type plasminogen activator
      using fluoresceinated uPA.
AB  - The urokinase-type plasminogen activator (uPA) is a serine protease that plays a
      crucial role in blood coagulation and in tumor invasion and metastasis. uPA is a
      relatively large polypeptide and binds the uPA receptor (uPAR) with high affinity
      and specificity. Therefore, it was a good candidate for direct labeling with a
      fluorochrome for detection of the uPAR. We have produced a fluorescein (FITC)
      labeled human uPA using a conjugation procedure that did not significantly alter
      its binding characteristics to the uPAR. Thirty nM FITC-uPA efficiently stains 2
      x 10(5) uPAR-transfected mouse cells in suspension, as determined by flow
      cytometric analysis. One microgram of FITC-uPA efficiently stains 2 x 10(5) uPAR
      transfectants grown on slides and analyzed by fluorescence optical microscopy.
      Human cell lines expressing the endogenous uPAR were stained with similar
      efficiency. Fixation in paraformaldehyde only slightly reduced the efficiency of
      staining of both transfectants and cell lines. These characteristics allow the
      use of FITC-uPA in both static and dynamic morphological studies of uPAR
      expressing cells.

PMID- 9283617
TI  - Automated double labeling of proliferation and apoptosis in glutathione S
      transferase-positive hepatocytes in rats.
AB  - Immunohistochemical markers for proliferation (bromodeoxyuridine, BrdU) and
      apoptosis (in situ terminal deoxynucleotide transferase dUTP nick end-labeling,
      TUNEL) were localized within glutathione S-transferase (GSTP)-positive hepatic
      foci in rats. Using the TechMate Automated Staining System (BioTek Solutions:
      Santa Barbara, CA), formalin-fixed, paraffin-embedded sections were run through a
      double-label avidin-blotin-immunoperoxidase protocol in less than 10 hr. Steam
      heat-induced epitope retrieval and/or proteolytic digestion preceded each
      labeling procedure. Color development was achieved using diaminobenzidine (DAB)
      with nickel enhancement for BrdU and TUNEL and VIP for GSTP. Results illustrate
      clear staining, brown-black BrdU-positive nuclei or TUNEL-positive apoptotic
      bodies within purple GSTP-positive hepatocytes. This automated procedure provides
      a method to easily identify and quantitate proliferating or apoptotic cells
      within foci of altered hepatocytes in rat liver and may have general applications
      for studies of cell or tissue kinetics during development, differentiation, and
      various pathological conditions in animals and humans.

PMID- 9283619
TI  - Continuous wavelet transform of aortic pressure oscillations in anesthetized
      dogs: effects of 45 degrees tilting.
AB  - The time-frequency analysis of signals by means of continuous wavelet transform
      (CWT) was applied to blood pressure oscillations recorded from the aorta of
      anesthetized dogs. This method yielded two and three-dimensional representations
      of either the module or phase in function of time, in contrast with the fast
      Fourier transform (FFT) which gives the spectrum in the frequency domain. From
      the CWT of arterial pressure oscillations we obtained visual information on
      aortic valves closure, heart rate, respiratory rate and smooth muscle
      contractions in arterial and arteriolar walls (very low frequency component). The
      objective of this study was to analyze the frequency-time behavior in two and
      three-dimensional cardiovascular changes during 45 degrees head-up and head-down
      tilts, compared with zero degree supine position. In eight pentobarbitone
      anesthetized dogs, the postural changes were repeated for more than ten times in
      each one. Heart rate variability was derived by applying a new mathematical
      procedure. We utilized the pronounced changes of heart rate during each
      respiratory cycle (inspiratory tachycardia and expiratory bradycardia) to
      establish a correlation with the arterial pressure fluctuations during normal and
      tilting conditions. Significant differences in heart rate were observed between
      the 45 degrees head-up and head-down tilts, compared with the supine position.
      The results show that anesthetized dogs might constitute an appropriate model
      where to study orthostatic hypotension and microgravity blood shifts.

PMID- 9283620
TI  - Development of a radioimmunoassay for Cebus apella prolactin.
AB  - Prolactin (PRL) is a pituitary hormone that plays important roles in mammalian
      reproductive physiology, specially lactation. The regulation of PRL secretion
      shows important species differences. To study PRL regulation in a subhuman
      primate, the Cebus apella, we developed an heterologous radioimmunoassay using an
      antibody against rhesus PRL (anti-m5PRL) and a Cebus apella pituitary extract as
      PRL standard. The assay has a sensitivity that allows measurements of cebus PRL
      in small amounts of Cebus apella plasma obtained from animals in different
      physiological conditions. Plasma cebus PRL concentrations (+/-SEM) varied in
      different reproductive stages. PRL concentration in adult Cebus apella females
      that have regular menstrual cycles (161.6 +/- 15.0 mIU/ml) was similar to that
      found in adult (100.3 +/- 7.6 mIU/ml) and prepuberal males (101.2 +/- 3.9
      mIU/ml). PRL concentration was higher in pregnant (677.8 +/- 11.8 mIU/ml) and in
      nursing (625.0 +/- 47.0 mIU/ml) Cebus apella females than in 15-d post-partum non
      nursing (369.0 +/- 19.0 mIU/ml) and cycling females. PRL concentration in Cebus
      apella newborns (719.0 +/- 49.2 mIU/ ml) was similar to that found in pregnant
      and nursing females, and higher than in the other females as well as adult and
      prepuberal males. These differences in PRL concentration in different
      physiological conditions are similar to that observed in humans and other
      primates. A PRL response to thyrotropin releasing hormone (TRH) was demonstrated
      in 2 nursing Cebus apella females, similar to the response found in nursing woman
      and rhesus. Altogether, the data presented support the proposal that the assay
      developed to measure PRL in Cebus apella is an adequate tool to study the
      physiology of PRL in this species.

PMID- 9283621
TI  - Hydrocortisone regulates types I and III collagen gene expression and collagen
      synthesis in human marrow stromal cells.
AB  - Hematopoiesis is the resultant of the orderly molecular and cellular interactions
      between progenitor cells and stroma. In vitro studies (Dexter-type cultures) have
      shown that initiation of hematopoiesis only occurs after establishment of a
      hydrocortisone-dependent layer of stromal cells. Although the molecular basis for
      the requirement of hydrocortisone are not well understood, data have shown that
      synthesis/assembly of extracellular matrix molecules (proteoglycans and
      fibronectin) is regulated by hydrocortisone. Since interstitial collagens are
      abundantly expressed in the marrow stroma, we investigated whether hydrocortisone
      may also modulate the expression of collagen types I and III. For these studies,
      human bone marrow fibroblast cultures were grown in standard culture medium
      either in the absence or presence of 10(-7) M hydrocortisone. Under both
      conditions, bone marrow fibroblasts synthesized collagen types I and III, and
      expressed the respective genes. However, hydrocortisone produced a decrease in
      the synthesis of interstitial collagens and also in the relative abundance of pro
      alpha 1(I) and pro-alpha 1(III) mRNAs. The results of this study are consistent
      with the assumption that glucocorticoids regulate the expression of several
      extracellular matrix molecules in the marrow stroma and thus permit in vitro
      hematopoiesis to occur.

PMID- 9283622
TI  - Localization of NMDA receptors in the cerebral cortex: a schematic overview.
AB  - The fundamental role of N-methyl-D-aspartate (NMDA) receptors in many cortical
      functions has been firmly defined, as has its involvement in a number of
      neurological and psychiatric diseases. However, until recently very little was
      known about the anatomical localization of NMDA receptors in the cerebral cortex
      of mammals. The recent application of molecular biological techniques to the
      study of NMDA receptors has provided specific tools which have greatly expanded
      our understanding of the localization of NMDA receptors in the cerebral cortex.
      In particular, immunocytochemical studies on the distribution of cortical NMDA
      receptors have shown that NMDA receptors are preferentially localized on
      dendritic spines, have disclosed an unknown fraction of presynaptic NMDA
      receptors on both excitatory and inhibitory axon terminals, and demonstrated that
      cortical astrocytes do express NMDA receptors. These studies suggest that the
      effects induced by the activation of NMDA receptors are not due solely to the
      opening of NMDA channels on neuronal postsynaptic membranes, as previously
      assumed, but that the activation of presynaptic and glial NMDA receptors may
      mediate part of these effects.

PMID- 9283623
TI  - Photochemistry and photobiology of actinic erythema: defensive and reparative
      cutaneous mechanisms.
AB  - Sunlight is part of our everyday life and most people accept it as beneficial to
      our health. With the advance of our knowledge in cutaneous photochemistry,
      photobiology and photomedicine over the past four decades, the terrestrial solar
      radiation has become a concern of dermatologists and is considered to be a major
      damaging environmental factor for our skin. Most photobiological effects (e.g.,
      sunburn, suntanning, local and systemic immunosuppression, photoaging or
      dermatoheliosis, skin cancer and precancer, etc.) are attributed to ultraviolet
      radiation (UVR) and more particularly to UVB radiation (290-320 nm). UVA
      radiation (320-400 nm) also plays an important role in the induction of erythema
      by the photosensitized generation of reactive oxygen species (singlet oxygen
      (1O2), superoxide (O2.-) and hydroxyl radicals (.OH)) that damage DNA and
      cellular membranes, and promote carcinogenesis and the changes associated with
      photoaging. Therefore, research efforts have been directed at a better
      photochemical and photobiological understanding of the so-called sunburn
      reaction, actinic or solar erythema. To survive the insults of actinic damage,
      the skin appears to have different intrinsic defensive mechanisms, among which
      antioxidants (enzymatic and non-enzymatic systems) play a pivotal role. In this
      paper, we will review the basic aspects of the action of UVR on the skin: a)
      photochemical reactions resulting from photon absorption by endogenous
      chromophores; b) the lipid peroxidation phenomenon, and c) intrinsic defensive
      cutaneous mechanisms (antioxidant systems). The last section will cover the
      inflammatory response including mediator release after cutaneous UVR exposure and
      adhesion molecule expression.

PMID- 9283625
TI  - Effect of FSH and insulin on lipogenesis in cultures of Sertoli cells from
      immature rats.
AB  - Follicle-stimulating hormone (FSH) and insulin regulate glycide metabolism in
      Sertoli cells, thus stimulating lactate production. These stimulatory effects of
      FSH and insulin do not require protein synthesis, suggesting a modulation of
      enzyme activity and/or regulation of glucose transport. The present investigation
      was performed to characterize the hormonal control of lipid metabolism in Sertoli
      cells. The data indicate that FSH and insulin have a regulatory effect on lipid
      metabolism in Sertoli cells. After 8 h of preincubation with insulin (5
      micrograms/ml), the activity of the enzyme ATP-citrate lyase in cultured Sertoli
      cells was increased from 0.19 to 0.34 nmol NAD+ formed microgram protein-1 min-1.
      FSH (100 ng/ml) had no effect on this enzyme. Glycerol phosphate dehydrogenase
      activity was not affected by any of the hormones tested. When Sertoli cells from
      19-day old rats were incubated with [1,2-14C]acetate for 90 or 360 min, the [14C]
      label was present predominantly in triglyceride and phospholipid fractions with
      minor amounts in other lipids. In Sertoli cells pretreated for 16 h with insulin
      and FSH, an increase in acetate incorporation into lipids was observed. Most of
      the label was in esterified lipids and this percentage increased with the time of
      treatment; this increase was remarkable in triglycerides of control cells (18.8%
      to 30.6%). Since Sertoli cell triglycerides participate in the control of
      spermatogenesis, the present data suggest that the hormonal control of lipid
      metabolism in Sertoli cells is important not only for maintaining the energy of
      the cell itself, but also for the control of the spermatogenesis process.

PMID- 9283624
TI  - Connexin domains relevant to the chemical gating of gap junction channels.
AB  - Most cells exchange ions and small metabolites via gap junction channels. These
      channels are made of two hemichannels (connexons), each formed by the radial
      arrangement of six connexin (Cx) proteins. Connexins span the bilayer four times
      (M1-M4) and have both amino- and carboxy-termini (NT, CT) at the cytoplasmic side
      of the membrane, forming two extracellular loops (E1, E2) and one inner (IL)
      loop. The channels are regulated by gates that close with cytosolic acidification
      (e.g., CO2 treatment) or increased calcium concentration, possibly via calmodulin
      activation. Although gap junction regulation is still unclear, connexin domains
      involved in gating are being defined. We have recently focused on the CO2 gating
      sensitivity of Cx32, Cx38 and various mutants and chimeras expressed in Xenopus
      oocytes and studied by double voltage clamp. Cx32 is weakly sensitive to CO2,
      whereas Cx38 is highly sensitive. A Cx32 chimera containing the second half of
      the inner loop (IL2) of Cx38 was as sensitive to CO2 as Cx38, indicating that
      this domain plays an important role. Deletion of CT by 84% did not affect CO2
      sensitivity, but replacement of 5 arginines (R) with asparagines (N) at the
      beginning of CT (C1) greatly enhanced the CO2 sensitivity of Cx32. This suggests
      that whereas most of CT is irrelevant, positive charges of C1 maintain the CO2
      sensitivity of Cx32 low. As a hypothesis we have proposed a model that involves
      charge interaction between negative residues of the beginning of IL (IL1) and
      positive residues of either C1 or IL2. Open and closed channels would result from
      IL1-C1 and IL1-IL2 interactions, respectively.

PMID- 9283627
TI  - A 28-fold increase in secretory protein synthesis is associated with DNA puff
      activity in the salivary gland of Bradysia hygida (Diptera, Sciaridae).
AB  - When the first group of DNA puffs is active in the salivary gland regions S1 and
      S3 of Bradysia hygida larvae, there is a large increase in the production and
      secretion of new salivary proteins demonstrable by [3H]-Leu incorporation. The
      present study shows that protein separation by SDS-PAGE and detection by
      fluorography demonstrated that these polypeptides range in molecular mass from
      about 23 to 100 kDa. Furthermore, these proteins were synthesized mainly in the
      S1 and S3 salivary gland regions where the DNA puffs C7, C5, C4 and B10 are
      conspicuous, while in the S2 region protein synthesis was very low. Others have
      shown that the extent of amplification for DNA sequences that code for mRNA in
      the DNA puffs C4 and B10 was about 22 and 10 times, respectively. The present
      data for this group of DNA puffs are consistent with the proposition that gene
      amplification is necessary to provide some cells with additional gene copies for
      the production of massive amounts of proteins within a short period of time.

PMID- 9283626
TI  - Aluminum induces lipid peroxidation and aggregation of human blood platelets.
AB  - Aluminum (Al3+) intoxication is thought to play a major role in the development
      of Alzheimer's disease and in certain pathologic manifestations arising from long
      term hemodialysis. Although the metal does not present redox capacity, it can
      stimulate tissue lipid peroxidation in animal models. Furthermore, in vitro
      studies have revealed that the fluoroaluminate complex induces diacylglycerol
      formation, 43-kDa protein phosphorylation and aggregation. Based on these
      observations, we postulated that Al(3+) -induced blood platelet aggregation was
      mediated by lipid peroxidation. Using chemiluminescence (CL) of luminol as an
      index of total lipid peroxidation capacity, we established a correlation between
      lipid peroxidation capacity and platelet aggregation. Al3+ (20-100 microM)
      stimulated CL production by human blood platelets as well as their aggregation.
      Incubation of the platelets with the antioxidants nor-dihydroguaiaretic acid
      (NDGA) (100 microM) and n-propyl gallate (NPG) (100 microM), inhibitors of the
      lipoxygenase pathway, completely prevented CL and platelet aggregation. Acetyl
      salicylic acid (ASA) (100 microM), an inhibitor of the cyclooxygenase pathway,
      was a weaker inhibitor of both events. These findings suggest that Al3+
      stimulates lipid peroxidation and the lipoxygenase pathway in human blood
      platelets thereby causing their aggregation.

PMID- 9283628
TI  - Changes in protein profile during coagulation of latex from Carica papaya.
AB  - We describe the changes in peptide composition by SDS-PAGE analysis of latex from
      Carica papaya collected at various times after incision of the unripe fruit. The
      data show that during latex coagulation several peptides are processed in an
      orderly fashion.

PMID- 9283629
TI  - Release of plasma atrial natriuretic peptide after volume expansion is not
      related to pituitary-adrenal axis diurnal variation in normal subjects.
AB  - The existence of a circadian rhythm of atrial natriuretic peptide (ANP) in humans
      is controversial. We studied the plasma ANP response to isotonic blood volume
      expansion in the morning and in the afternoon and its relationship with
      adrenocorticotropic hormone (ACTH)-cortisol diurnal variation in seven normal
      subjects. Basal plasma ANP level was similar in the morning (19.6 +/- 2.4 pg/ml)
      and in the afternoon (21.8 +/- 4.8 pg/ml). The ANP peak obtained with saline
      infusion (0.9% NaCl, 12 ml/kg) in the morning (49.4 +/- 8 pg/ml) did not differ
      from that obtained in the afternoon (60.3 +/- 10.1 pg/ml). There was no
      correlation between the individual mean cortisol and ACTH levels and the ANP peak
      obtained with saline infusion. These data indicate no diurnal variation in plasma
      ANP secretion induced by blood volume expansion and no relationship between
      plasma ANP peak and ACTH-cortisol diurnal variation.

PMID- 9283630
TI  - Morphometry and acetylcholinesterase activity of the myenteric plexus of the wild
      mouse Calomys callosus.
AB  - The myenteric plexus of the digestive tract of the wild mouse Calomys callosus
      was examined using a histochemical method that selectively stains nerve cells,
      and the acetylcholinesterase (AChE) histochemical technique in whole-mount
      preparations. Neuronal density was 1,500 +/- 116 neurons/cm2 (mean +/- SEM) in
      the esophagus, 8,900 +/- 1,518 in the stomach, 9,000 +/- 711 in the jejunum and
      13,100 +/- 2,089 in the colon. The difference in neuronal density between the
      esophagus and other regions was statistically significant. The neuron profile
      area ranged from 45 to 1,100 microns2. The difference in nerve cell size between
      the jejunum and other regions was statistically significant. AChE-positive nerve
      fibers were distributed within the myenteric plexus which is formed by a primary
      meshwork of large nerve bundles and a secondary meshwork of finer nerve bundles.
      Most of the nerve cells displayed AChE activity in the cytoplasm of different
      reaction intensities. These results are important in order to understand the
      changes occurring in the myenteric plexus in experimental Chagas' disease.

PMID- 9283631
TI  - Contrast sensitivity to angular frequency stimuli is higher than that for
      sinewave gratings in the respective middle range.
AB  - This study compares contrast thresholds for sinewave gratings, or spatial
      frequencies (1/CSF) with contrast thresholds for angular frequencies (1/aCSF) and
      for radial frequencies, or Jzero targets (1/rCSF). Observers had to differentiate
      between one of these frequency stimuli and a stimulus at mean luminance within a
      forced-choice procedure. All measurements were made with the same equipment,
      methods and subjects. Our results show higher sensitivity to, or lower thresholds
      for, angular frequencies when compared to either sinewave gratings or Jzero
      targets. Contrast values in arbitrary units, in the lower threshold range for
      angular frequencies, were about half those required to differentiate sinewave
      gratings from mean luminance in its most sensitive range.

PMID- 9283632
TI  - Circadian time-dependent effects of fencamfamine on inhibition of dopamine uptake
      and release in rat striatal slices.
AB  - Fencamfamine (FCF) is a central stimulant that facilitates central dopaminergic
      transmission through inhibition of dopamine uptake and enhanced release of the
      transmitter. We evaluated the changes in the inhibition of uptake and the release
      of striatal [3H]-dopamine at 9:00 and 21:00 h, times corresponding to maximal and
      minimal behavioral responses to FCF, respectively. Adult male Wistar rats (200
      250 g) maintained on a 12-h light/12-h dark cycle (lights on at 7:00 h) were
      used. In the behavioral experiments the rats (N = 8 for each group) received FCF
      (3.5 mg/kg, ip) or saline at 9:00 or 21:00 h. Fifteen minutes after treatment the
      duration of activity (sniffing, rearing and locomotion) was recorded for 120 min.
      The basal motor activity was higher (28.6 +/- 4.2 vs 8.4 +/- 3.5 s) after saline
      administration at 21:00 h than at 9:00 h. FCF at a single dose significantly
      enhanced the basal motor activity (38.3 +/- 4.5 vs 8.4 +/- 3.5 s) and increased
      the duration of exploratory activity (38.3 +/- 4.5 vs 32.1 +/- 4.6 s) during the
      light, but not the dark phase. Two other groups of rats (N = 6 for each group)
      were decapitated at 9:00 and 21:00 h and striata were dissected for dopamine
      uptake and release assays. The inhibition of uptake and release of [3H]-dopamine
      were higher at 9:00 than at 21:00 h, suggesting that uptake inhibition and the
      release properties of FCF undergo daily variation. These data suggest that the
      circadian time-dependent effects of FCF might be related to a higher
      susceptibility of dopamine presynaptic terminals to the action of FCF during the
      light phase which corresponds to the rats' resting period.

PMID- 9283633
TI  - Rapid eye movement (REM) sleep deprivation reduces rat frontal cortex
      acetylcholinesterase (EC 3.1.1.7) activity.
AB  - Rapid eye movement (REM) sleep deprivation induces several behavioral changes.
      Among these, a decrease in yawning behavior produced by low doses of cholinergic
      agonists is observed which indicates a change in brain cholinergic
      neurotransmission after REM sleep deprivation. Acetylcholinesterase (Achase)
      controls acetylcholine (Ach) availability in the synaptic cleft. Therefore,
      altered Achase activity may lead to a change in Ach availability at the receptor
      level which, in turn, may result in modification of cholinergic
      neurotransmission. To determine if REM sleep deprivation would change the
      activity of Achase, male Wistar rats, 3 months old, weighing 250-300 g, were
      deprived of REM sleep for 96 h by the flower-pot technique (N = 12). Two
      additional groups, a home-cage control (N = 6) and a large platform control (N =
      6), were also used. Achase was measured in the frontal cortex using two different
      methods to obtain the enzyme activity. One method consisted of the obtention of
      total (900 g supernatant), membrane-bound (100,000 g pellet) and soluble (100,000
      g supernatant) Achase, and the other method consisted of the obtention of a
      fraction (40,000 g pellet) enriched in synaptic membrane-bound enzyme. In both
      preparations, REM sleep deprivation induced a significant decrease in rat frontal
      cortex Achase activity when compared to both home-cage and large platform
      controls. REM sleep deprivation induced a significant decrease of 16% in the
      membrane-bound Achase activity (nmol thiocholine formed min-1 mg protein-1) in
      the 100,000 g pellet enzyme preparation (home-cage group 152.1 +/- 5.7, large
      platform group 152.7 +/- 24.9 and REM sleep-deprived group 127.9 +/- 13.8). There
      was no difference in the soluble enzyme activity. REM sleep deprivation also
      induced a significant decrease of 20% in the enriched synaptic membrane-bound
      Achase activity (home-cage group 126.4 +/- 21.5, large platform group 127.8 +/-
      20.4, REM sleep-deprived group 102.8 +/- 14.2). Our results suggest that REM
      sleep deprivation changes Ach availability at the level of its receptors through
      a decrease in Achase activity.

PMID- 9283634
TI  - Role of endothelium in angiotensin II formation by the rat aorta and mesenteric
      arterial bed.
AB  - We investigated the angiotensin II (Ang II)-generating system by analyzing the
      vasoconstrictor effect of Ang II, angiotensin J (Ang I), and tetradecapeptide
      (TDP) renin substrate in the absence and presence of inhibitors of the renin
      angiotensin system in isolated rat aortic rings and mesenteric arterial beds with
      and without functional endothelium. Ang II, Ang I, and TDP elicited a dose
      dependent vasoconstrictor effect in both vascular preparations that was
      completely blocked by the Ang II receptor antagonist saralasin (50 nM). The
      angiotensin converting enzyme (ACE) inhibitor captopril (36 microM) completely
      inhibited the vasoconstrictor effect elicited by Ang I and TDP in aortic rings
      without affecting that of Ang II. In contrast, captopril (36 microM)
      significantly reduced (80-90%) the response to bolus injection of Ang I, without
      affecting those to Ang II and TDP in mesenteric arteries. Mechanical removal of
      the endothelium greatly potentiated (70-95%) the vasoconstrictor response to Ang
      II, Ang I, and TDP in aortic rings while these responses were unaffected by the
      removal of the endothelium of mesenteric arteries with sodium deoxycholate
      infusion. In addition, endothelium disruption did not change the pattern of
      response elicited by these peptides in the presence of captopril. These findings
      indicate that the endothelium may not be essential for Ang II formation in rat
      mesenteric arteries and aorta, but it may modulate the response to Ang II.
      Although Ang II formation from Ang I is essentially dependent on ACE in both
      vessels, our results suggest the existence of an alternative pathway in the
      mesenteric arterial bed that may play an important role in Ang II generation from
      TDP in resistance but not in large vessels during ACE inhibition.

PMID- 9283635
TI  - Partial recovery of erythrocyte glycogen in diabetic rats treated with
      phenobarbital.
AB  - Erythrocytes may play a role in glucose homeostasis during the postprandial
      period. Erythrocytes from diabetic patients are defective in glucose transport
      and metabolism, functions that may affect glycogen storage. Phenobarbital, a
      hepatic enzyme inducer, has been used in the treatment of patients with non
      insulin-dependent diabetes mellitus (NIDDM), increasing the insulin-mediated
      glucose disposal. We studied the effects of phenobarbital treatment in vivo on
      glycemia and erythrocyte glycogen content in control and alloxan-diabetic rats
      during the postprandial period. In control rats (blood glucose, 73 to 111 mg/dl
      in femoral and suprahepatic veins) the erythrocyte glycogen content was 45.4 +/-
      1.1 and 39.1 +/- 0.8 micrograms/g Hb (mean +/- SEM, N = 4-6) in the femoral
      artery and vein, respectively, and 37.9 +/- 1.1 in the portal vein and 47.5 +/-
      0.9 in the suprahepatic vein. Diabetic rats (blood glucose, 300-350 mg/dl)
      presented low (P < 0.05) erythrocyte glycogen content, i.e., 9.6 +/- 0.1 and 7.1
      +/- 0.7 micrograms/g Hb in the femoral artery and vein, respectively, and 10.0 +/
      0.7 and 10.7 +/- 0.5 in the portal and suprahepatic veins, respectively. After
      10 days of treatment, phenobarbital (0.5 mg/ml in the drinking water) did not
      change blood glucose or erythrocyte glycogen content in control rats. In diabetic
      rats, however, it lowered (P < 0.05) blood glucose in the femoral artery (from
      305 +/- 18 to 204 +/- 45 mg/dl) and femoral vein (from 300 +/- 11 to 174 +/- 48
      mg/dl) and suprahepatic vein (from 350 +/- 10 to 174 +/- 42 mg/ dl), but the
      reduction was not sufficient for complete recovery. Phenobarbital also stimulated
      the glycogen synthesis, leading to a partial recovery of glycogen stores in
      erythrocytes. In treated rats, erythrocyte glycogen content increased to 20.7 +/-
      3.8 micrograms/g Hb in the femoral artery and 30.9 +/- 0.9 micrograms/g Hb in the
      suprahepatic vein (P < 0.05). These data indicate that phenobarbital activated
      some of the insulin-stimulated glucose metabolism steps which were depressed in
      diabetic erythrocytes, supporting the view that erythrocytes participate in
      glucose homeostasis.

PMID- 9283636
TI  - Spreading depression is facilitated in adult rats previously submitted to short
      episodes of malnutrition during the lactation period.
AB  - Lactating rat dams were submitted to short episodes (1, 2 or 3 weeks) of
      nutritional restriction by receiving the "regional basic diet" (RBD, with 8%
      protein) of low-income human populations of Northeast Brazil. Their pups were
      then studied regarding the developmental effects on body and brain weights. When
      the rats reached adulthood, cortical susceptibility to the phenomenon of
      spreading depression (SD) was evaluated by performing electrophysiological
      recordings on the surface of the cerebral cortex. SD was elicited at 20-min
      intervals by applying 2% KCl for 1 min to a site on the frontal cortex and its
      occurrence was monitored at 2 sites in the parietal region by recording the
      electrocorticogram and the slow potential change of SD. When compared to control
      rats fed a commercial diet with 23% protein, early malnourished rats showed
      deficits in body and brain weights (10% to 60% and 3% to 15%, respectively), as
      well as increases in velocity of SD propagation (10% to 20%). These effects were
      directly related to the duration of maternal dietary restriction, with pups
      malnourished for 2 or 3 weeks presenting more intense weight and SD changes than
      those malnourished for 1 week. The effects of 1-week restrictions on SD were less
      evident in the pups malnourished during the second week of lactation and were
      more evident in pups receiving the RBD during the third week. The results
      indicate that short episodes of early malnutrition during the suckling period can
      affect body and brain development, as well as the cortical susceptibility to SD
      during adulthood. The data also suggest that the third week of lactation is the
      period during which the brain is most sensitive to malnutrition, concerning the
      effects on SD.

PMID- 9283637
TI  - Monosodium glutamate (MSG)-obese rats develop glucose intolerance and insulin
      resistance to peripheral glucose uptake.
AB  - Different levels of insulin sensitivity have been described in several animal
      models of obesity as well as in humans. Monosodium glutamate (MSG)-obese mice
      were considered not to be insulin resistant from data obtained in oral glucose
      tolerance tests. To reevaluate insulin resistance by the intravenous glucose
      tolerance test (IVGTT) and by the clamp technique, newborn male Wistar rats (N =
      20) were injected 5 times, every other day, with 4 g/kg MSG (N = 10) or saline
      (control; N = 10) during the first 10 days of age. At 3 months, the IVGTT was
      performed by injecting glucose (0.75 g/kg) through the jugular vein into freely
      moving rats. During euglycemic clamping plasma insulin levels were increased by
      infusing 3 mU.kg-1.min-1 of regular insulin until a steady-state plateau was
      achieved. The basal blood glucose concentration did not differ between the two
      experimental groups. After the glucose load, increased values of glycemia (P <
      0.001) in MSG-obese rats occurred at minute 4 and from minute 16 to minute 32.
      These results indicate impaired glucose tolerance. Basal plasma insulin levels
      were 39.9 +/- 4 microU/ml in control and 66.4 +/- 5.3 microU/ml in MSG-obese
      rats. The mean post-glucose area increase of insulin was 111% higher in MSG-obese
      than in control rats. When insulinemia was clamped at 102 or 133 microU/ml in
      control and MSG rats, respectively, the corresponding glucose infusion rate
      necessary to maintain euglycemia was 17.3 +/- 0.8 mg.kg-1.min-1 for control rats
      while 2.1 +/- 0.3 mg.kg-1.min-1 was sufficient for MSG-obese rats. The 2-h
      integrated area for total glucose metabolized, in mg.min.dl-1, was 13.7 +/- 2.3
      vs 3.3 +/- 0.5 for control and MSG rats, respectively. These data demonstrate
      that MSG-obese rats develop insulin resistance to peripheral glucose uptake.

PMID- 9283638
TI  - Bovine serum albumin potentiates caffeine- or ATP-induced tension in human
      skinned skeletal muscle fibers.
AB  - Human skinned muscle fibers were used to investigate the effects of bovine serum
      albumin (BSA) on the tension/pCa relationship and on the functional properties of
      the Ca(2+)-release channel of the sarcoplasmic reticulum (SR). In both fast- and
      slow-type fibers, identified by their tension response to pSr 5.0, BSA (0.7-15
      microM) had no effect on the Ca2+ affinity of the contractile proteins and
      elicited no tension per se in Ca(2+)-loaded fibers. In contrast, BSA (> 1.0
      microM) potentiated the caffeine-induced tension in Ca(2+)-loaded fibers, this
      effect being more intense in slow-type fibers. Thus, BSA reduced the threshold
      caffeine concentration required for eliciting detectable tension, and increased
      the amplitude, the rate of rise and the area under the curve of caffeine-induced
      tension. BSA also potentiated the tension elicited in Ca(2+)-loaded fibers by low
      Mg2+ solutions containing 1.0 mM free ATP. These results suggest that BSA
      modulates the response of the human skeletal muscle SR Ca(2+)-release channel to
      activators such as caffeine and ATP.

PMID- 9283640
TI  - Effect of ventilation on systemic blood flow evaluated by
      echodopplercardiography.
AB  - Systemic blood flow (Q) was measured by echodopplercardiography in 5 normal young
      adult males during apnea, eupnea and tachypnea. Measurements were made in a
      recumbent posture at 3-min intervals. Tachypnea was attained by doubling the
      respiratory frequency at eupnea at a constant tidal volume. An open glottis was
      maintained during apnea at the resting respiratory level. The Q values were
      positively correlated with the respiratory frequency, decreasing from eupnea to
      apnea and increasing from eupnea to tachypnea (P < 0.05). These data demonstrate
      that echodopplercardiography, a better qualified tool for this purpose, confirms
      the positive and progressive effects of ventilation on systemic blood flow, as
      suggested by previous studies based on diverse technical approaches.

PMID- 9283639
TI  - Increased angiotensin-converting enzyme activity in the left ventricle after
      infarction.
AB  - An increase in angiotensin-converting enzyme (ACE) activity has been observed in
      the heart after myocardial infarction (MI). Since most studies have been
      conducted in chronically infarcted individuals exhibiting variable degrees of
      heart failure, the present study was designed to determine ACE activity in an
      earlier phase of MI, before heart failure development. MI was produced in 3-month
      old male Wistar rats by ligation of the anterior branches of the left coronary
      artery, control rats underwent sham surgery and the animals were studied 7 or 15
      days later. Hemodynamic data obtained for the anesthetized animals showed normal
      values of arterial blood pressure and of end-diastolic pressure in the right and
      left ventricular cavities of MI rats. Right and left ventricular (RV, LV) muscle
      and scar tissue homogenates were prepared to determine ACE activity in vitro by
      measuring the velocity of His-Leu release from the synthetic substrate Hyp-His
      Leu. ACE activity was corrected to the tissue wet weight and is reported as nmol
      His-Leu g-1 min-1. No significant change in ACE activity in the RV homogenates
      was demonstrable. A small nonsignificant increase of ACE activity (11 +/- 9%; P >
      0.05) was observed 7 days after MI in the surviving left ventricular muscle. Two
      weeks after surgery, however, ACE activity was 46 +/- 11% (P < 0.05) higher in
      infarcted rats compared to sham-operated rats. The highest ACE activity was
      demonstrable in the scar tissue homogenate. In rats studied two weeks after
      surgery, ACE activity in the LV muscle increased from 105 +/- 7 nmol His-Leu g-1
      min-1 in control hearts to 153 +/- 11 nmol His-Leu g-1 min-1 (P < 0.05) in the
      remaining LV muscle of MI rats and to 1051 +/- 208 nmol His-Leu g-1 min-1 (P <
      0.001) in the fibrous scar. These data indicate that ACE activity increased in
      the heart after infarction before heart failure was demonstrable by hemodynamic
      measurements. Since the blood vessels of the scar drain to the remaining LV
      myocardium, the high ACE activity present in the fibrous scar may increase the
      angiotensin II concentration and decrease bradykinin in the cardiac tissues
      surrounding the infarcted area. The increased angiotensin II in the fibrous scar
      may contribute to the reactive fibrosis and hypertrophy in the left ventricular
      muscle surviving infarction.

PMID- 9283641
TI  - Control of schistosomiasis mansoni in Ravena (Sabara, state of Minas Gerais,
      Brazil) through water supply and quadrennial treatments.
AB  - In this study, the results obtained in a control programme of schistosomiasis in
      Ravena (Sabara, Minas Gerais) between 1980 and 1992 are evaluated. Control
      measures used in this programme were: specific treatment of the people infected
      with Schistosoma mansoni at four year-intervals (1980/84/88) and the supply of
      tap water to 90% of the residences in 1980. A significant reduction of the
      prevalence (36.7% to 11.5%, p < or = 0.05) and of the intensity of the infection
      (228.9 eggs per gram of feces (epg), s = 3.7 to 60.3 epg, s = 3.5, p < or = 0.05)
      was observed. No cases of the severe form of the disease were diagnosed in the
      area. Factors independently associated with the infection were in 1980 daily sand
      extraction and the lack of tap water in residences and in 1992 daily sand
      extraction and fishing and weekly swimming. Concluding, the supply of tap water
      together with quadrennial treatments significantly diminished both the prevalence
      and intensity of the S. mansoni infection, with the additional gain of persistent
      low indices even after four-year intervals between the treatments.

PMID- 9283642
TI  - Isolation of fungi from nature in the region of Botucatu, state of Sao Paulo,
      Brazil, an endemic area of paracoccidioidomycosis.
AB  - In an attempt to isolate Paracoccidioides brasiliensis from nature 887 samples of
      soil from Botucatu, SP, Brazil, were collected cultured in brain heart infusion
      agar supplemented with dextrose, in potato dextrose agar and in yeast extract
      starch dextrose agar, all with antibiotics, at 25 degrees and 37 degrees C. Five
      thermo-dependent dimorphic fungi morphologically resembling P. brasiliensis were
      isolated; two from armadillo holes; further studies of the biology, antigenicity
      and genetic features of the five dimorphic fungi are necessary to clarify their
      taxonomy and their possible relation to P. brasiliensis. In addition, 98
      dematiaceous fungi and 581 different species of Aspergillus spp. were also
      isolated. Our findings emphasize that armadillos and their environment are
      associated with thermo-dimorphic fungi and confirm the ubiquity of pathogenic
      dematiaceous fungi and Aspergillus spp.

PMID- 9283643
TI  - Ecological interactions of visceral leishmaniasis in the state of Bahia, Brazil.
AB  - The laboratory and field observations summarized in this paper on visceral
      leishmaniasis ecology in the State of Bahia, Brazil are based on the author's
      observations over the past 35 years in a number of state's foci, public health
      records and literature citations. The disease is endemic with epidemic outbreaks
      occurring every ten years and its geographical distribution is expanding rapidly
      in the last years. Leishmania chagasi is the main ethiologic agent of the
      visceral leishmaniasis but Le. amazonensis s. lato was the only leishmania
      isolated by other authors from some visceral leishmaniasis human cases in the
      state. Lutzomyia longipalpis (with one or two spots on tergites III and IV and
      two sized different populations) was epidemiologically incriminated as the main
      vector. It was found naturally infected with promastigotes, and it was infected
      with four species of leishmanias in the laboratory. Although the experimental
      transmission of Le. amazonensis by the bite of Lu. longipalpis to hamsters was
      performed, the author was not successful in transmitting Le. chagasi in the same
      way. The dog is the most important domestic source for infection of the vector,
      however it is not a primary reservoir. The opossum Didelphis albiventris was
      found naturally infected with Le. chagasi but its role as reservoir is unknown.
      Foxes and rodents were not found infected with leishmanias in Bahia.

PMID- 9283644
TI  - Intestinal parasites in AIDS and +HIV patients in Uberlandia, Minas Gerais,
      Brazil.

PMID- 9283645
TI  - Simian malaria at two sites in the Brazilian Amazon--II. Vertical distribution
      and frequency of anopheline species inside and outside the forest.
AB  - An anopheline survey was carried out in two simian malaria areas in the Brazilian
      Amazon, Balbina and Samuel, to determine the potential vectors of Plasmodium
      brasilianum. The most abundant and/or acrodendrophilic anophelines in the forest
      and the most likely vector were Anopheles mediopunctatus, An. nuneztovari, An.
      oswaldoi, An. triannulatus and An. shannoni. An. darlingi and An. marajoara were
      captured essentially in anthropic habitats outside the forest and are unlikely to
      be involved in the transmission of P. brasilianum among monkeys within the
      forests and from monkeys to man in their surroundings in the Amazon.

PMID- 9283646
TI  - Phase I and II open clinical trials of a vaccine against Leishmania chagasi
      infections in dogs.

PMID- 9283647
TI  - Wild birds as reservoir of thermophilic enteropathogenic Campylobacter species in
      southern Chile.

PMID- 9283649
TI  - On Simulium (Pternaspatha), with description of a new species (Diptera
      Simuliidae).
AB  - Simulium (Pternaspatha) diamantinum n. sp. is described from females, males,
      pupae and larvae, collected at Mendoza, San Juan and Neuquen. Some specimens of
      this species from Laguna del Diamante were included before by Wygodzinsky and
      Coscaron (1967) in S. strigidorsum Enderlein. The new species is compared with
      closely related species of the S. (Pternaspatha) "nigristrigatum group". The
      following synonym is established: Simulium (Pternaspatha) bachmanni Wygodzinsky &
      Coscaron = Simulium (Pternaspatha) nigristrigatum (Enderlein).

PMID- 9283648
TI  - Infestation by ticks and detection of antibodies to spotted fever group
      rickettsiae in wild animals captured in the state of Sao Paulo, Brazil. A
      preliminary report.

PMID- 9283650
TI  - Description of Warileya lumbrerasi n. sp. (Diptera:Psychodidae) from Peru.
AB  - Warileya lumbrerasi n. sp. is described from the northern Peruvian Andes. This
      species was collected inside houses, and is the seventh species described within
      the genus Warileya Hertig, 1948.

PMID- 9283651
TI  - Occurrence of cystacanths of Centrorhynchus sp. (Acanthocephala:Centrorhynchidae)
      in toads of the genus Eupsophus in Chile.

PMID- 9283652
TI  - The need for an integrated approach to the taxonomy of neotropical Simuliidae,
      with special reference to larval colour.

PMID- 9283653
TI  - Spasskyellina mandi n. sp. (Proteocephalidea:Monticelliidae), parasite of
      Pimelodus ornatus Kner, 1857 (Pisces:Pimelodidae) of the Parana River, Parana,
      Brazil.
AB  - Spasskyellina mandi n. sp. (Proteocephalidea: Monticelliidae) is described from
      the Siluriform fish Pimelodus ornatus Kner, 1857, caught in the Parana River,
      Parana, Brazil. The new species differs from other species of the same genus
      mainly by a fewer number of testes and by a larger osmoregulatory canal. This is
      the second species of proteocephalidean cestode collected in P. ornatus.

PMID- 9283654
TI  - [External morphology of Triatoma rickmani Zeledon & Ponce, 1972 seen under
      scanning electron microscopy].
AB  - A male of Triatoma ryckmani Zeledon & Ponce, 1972, was studied by scanning
      electron microscopy. Only few specimens of this species are known. In this paper,
      some structures from the head, thorax, abdomen and distal region of the second
      leg are shown. Some of them could have taxonomic importance, as the oculo-ocellar
      region, the buccula, the anterolateral angle of the collar, the scutellum with
      the process longer than the main body, the stridulatory sulcus with an unusual
      backward vermiform area, and the tibia-tarsal articulation, with a spongy
      fossula. The last structure was absent in specimens previously studied (Lent &
      Wygodzinsky 1979). Differences between this specimen and others previously
      described by several authors are discussed.

PMID- 9283655
TI  - Dasybasis (Agelanius) cortesi, a new species of horse fly from Chile
      (Diptera:Tabanidae:Diachlorini).
AB  - The female and male of Dasybasis (Agelanius) cortesi, new species, is described
      and illustrated from specimens collected in the National Reserve of Rio Clarillo,
      Cordillera Province, Central Chile. Its relationships to other Dasybasis species
      are discussed.

PMID- 9283656
TI  - A low stringency polymerase chain reaction approach to the identification of
      Biomphalaria glabrata and B. tenagophila, intermediate snail hosts of Schistosoma
      mansoni in Brazil.
AB  - The low stringency-polymerase chain reaction (LS-PCR) with a pair of specific
      primers for the amplification of the 18S rRNA gene was evaluated as a means of
      differentiating between the two Schistosoma mansoni intermediate host species in
      Brazil: Biomphalaria glabrata and B. tenagophila. Individual snails obtained from
      different states of Brazil were used and the amplification patterns obtained
      showed a high degree of genetic variability in these species. Nevertheless, 4 and
      3 clearly defined specific diagnostic bands was observed in individuals from B.
      glabrata and B. tenagophila respectively. The detection of snail specific
      diagnostic bands suggests the possibility of reliable species differentiation at
      the DNA level using LS-PCR.

PMID- 9283657
TI  - HIV-1 isolation from plasma specimens. HEC/FIOCRUZ AIDS Clinical Research Group.

PMID- 9283658
TI  - Reliability of serological methods for detection of leishmaniasis in Portuguese
      domestic and wild reservoirs.
AB  - A direct agglutination test (DAT) and an immunofluorescence technique (IFAT) were
      compared for detection of Leishmania infantum infection in 43 dogs and five foxes
      from Alto-Douro and Arrabida, two known endemic areas in Portugal. In four dogs
      with proved canine leishmaniasis, both DAT and IFAT showed positive readings
      (titres > or = 1:320 and > or = 1:128). Of 34 samples collected from apparently
      healthy dogs, ten were positive by both serological tests and eight were
      serologically positive by one test or the other. Three foxes out of five captured
      in this area, scored titres indicative of leishmaniasis in both DAT and IFAT. The
      concordance between DAT and IFAT in all collected samples (48) was 81.25%.
      Considering these and previous studies in the adjacent Mediterranean areas, the
      seroprevalence of L. infantum infection in the canine and vulpine populations
      appear to be of high magnitude.

PMID- 9283660
TI  - Detection of extracellular proteases from microorganisms on agar plates.
AB  - We present herein an improved assay for detecting the presence of extracellular
      proteases from microorganisms on agar plates. Using different substrates
      (gelatin, BSA, hemoglobin) incorporated into the agar and varying the culture
      medium composition, we were able to detect proteolytic activities from
      Pseudomonas aeruginosa, Micrococcus luteus and Serratia marcescens as well as the
      influence that these components displayed in the expression of these enzymes. For
      all microorganisms tested we found that in agar-BHI or yeast extract medium
      containing gelatin the sensitivity of proteinase detection was considerably
      greater than in BSA-agar or hemoglobin-agar. However, when BSA or hemoglobin were
      added to the culture medium, there was an increase in growth along with a marked
      reduction in the amount of proteinase production. In the case of M. luteus the
      incorporation of glycerol in BHI or yeast extract gelatin-agar induced protease
      liberation. Our results indicate that the technique described here is of value
      for detecting extracellular proteases directly in the culture medium, by means of
      a qualitative assay, simple, inexpensive, straight forward method to assess the
      presence of the proteolytic activity of a given microorganism colony with great
      freedom in substrate selection.

PMID- 9283659
TI  - The serological differentiation of acute and chronic schistosomiasis japonica
      using IgA antibody to egg antigen.
AB  - Two groups of Schistosoma japonicum infected patients (acute and chronic) and non
      infected individuals were studied using IgA antibody to egg antigen (SEA) and IgG
      and IgM antibodies to keyhole limpet haemocyanin (KLH). The means and standard
      deviation of the optical density in ELISA of acute, chronic and negative groups
      for IgA anti-SEA were 583 +/- 124.7, 98.2 +/- 78.8 and 82.2 +/- 39.3,
      respectively. There was a statistically significance between acute patients and
      chronic patients (P < 0.01). The means and standard deviation of IgG and IgM
      antibodies to KLH were 501.5 +/- 150.6, 113.0 +/- 79.1, 28.8 +/- 56.3 and 413.6
      +/- 148.5, 70.2 +/- 14.8, 65.3 +/- 45.3, respectively. The detection results of
      IgA to SEA compared with the IgG and IgM to KLH did not demonstrate a significant
      difference (P < 0.01). The sensitivities of IgA to SEA and IgG and IgM antibodies
      to KLH for the detection of acute infection were 95.24%, 90.48% and 85.71%,
      respectively. Therefore, this study showed that the detection of IgA to SEA is
      also a useful new method for the serological differentiation of acute and chronic
      schistosomiasis japonica in humans.

PMID- 9283662
TI  - Invasion of HeLa cells by Providencia alcalifaciens presumably is plasmid
      encoded.

PMID- 9283661
TI  - The carbohydrate-binding specificity and molecular modelling of Canavalia
      maritima and Dioclea grandiflora lectins.
AB  - The carbohydrate-binding specificity of lectins from the seeds of Canavalia
      maritima and Dioclea grandiflora was studied by hapten-inhibition of
      haemagglutination using various sugars and sugar derivatives as inhibitors,
      including N-acetylneuraminic acid and N-acetylmuramic acid. Despite some
      discrepancies, both lectins exhibited a very similar carbohydrate-binding
      specificity as previously reported for other lectins from Diocleinae (tribe
      Phaseoleae, sub-tribe Diocleinae). Accordingly, both lectins exhibited almost
      identical hydropathic profiles and their three-dimensional models built up from
      the atomic coordinates of ConA looked very similar. However, docking experiments
      of glucose and mannose in their monosaccharide-binding sites, by comparison with
      the ConA-mannose complex used as a model, revealed conformational changes in side
      chains of the amino acid residues involved in the binding of monosaccharides.
      These results fully agree with crystallographic data showing that binding of
      specific ligands to ConA requires conformational chances of its monosaccharide
      binding site.

PMID- 9283663
TI  - Influence of the route of administration of pig-serum in the induction of hepatic
      septal fibrosis in rats.

PMID- 9283665
TI  - Susceptibility of Helicobacter pylori to metronidazole in a Brazilian population.

PMID- 9283664
TI  - Characterization and biological activity of a Brazilian isolate of Bacillus
      sphaericus (Neide) highly toxic to mosquito larvae.
AB  - Primary powders of Bacillus sphaericus strain S2 isolated from soil samples in
      Brazil, and strain 2362 were produced in a 14 liter fermentor. Growth patterns
      and sporulation observed in three trials with strains S2 and 2362 in the
      fermentor were similar. Second-instar larvae of Culex quinquefasciatus, Anopheles
      albimanus, Anopheles quadrimaculatus, and Aedes aegypti exposed for 48 hr to
      strain S2 responded with LC50 values of 0.25, 5.95, 12.28 and 140.0 ppb of
      lyophilized primary powder, respectively. Under the same conditions, strain 2362
      resulted in LC50 values of 0.39, 7.16, 16.93 and 307.0 ppb of lyophilized primary
      powder, respectively, in those mosquito larvae. Statistical analysis of the
      bioassay data did not show significant differences among LC50 values observed in
      B. sphaericus strains S2 and 2362, at the 0.05 level. Toxins of strains S2 and
      2362 were extracted at pH 12 with NaOH. Electrophoresis of the extracts in
      polyacrylamide gel under denaturing conditions revealed the 51 and 42 kDa toxins
      in both S2 and 2362 B. sphaericus strains. The presence of the 42 kDa peptide in
      the extracts was confirmed by Western blot and Elisa, with anti-42 kDa IgG
      previously prepared from strain 2362.

PMID- 9283666
TI  - Chromoblastomycosis murine model and in vitro test to evaluate the sensitivity of
      Fonsecaea pedrosoi to ketoconazole, itraconazole and saperconazole.
AB  - An experimental model of murine chromoblastomycosis and in vitro tests with
      Fonsecaea pedrosoi were used to test the sensitivity of this fungus to three
      different antimycotics. The experimental model was standardized in BALB/c mice
      inoculated intraperitoneally with a 10(6) CFU/ml suspension of a F. pedrosoi
      isolate. Clinical infection was evident after 5 days of inoculation. Three groups
      of 27 mice each were used in the experiment. One group was treated with
      ketoconazole (KTZ), another with itraconazole (ITZ) and the other with
      saperconazole (SPZ). Antimycotic therapy was continued for 21 days. The control
      group consisted of 40 mice which were inoculated, but not treated. Infection was
      documented by macroscopic and microscopic examination of affected tissue in
      addition to culture of tissue macerates. Minimal inhibitory concentrations (MIC)
      and minimal fungicidal concentrations (MFC) for the F. pedrosoi strain used were
      done. The in vitro results showed that SPZ was the most active with MIC 0.01
      microgram/ml and MFC 0.1 microgram/ml, followed by ITZ. SPZ was also the most
      effective in vivo since 63% of the treated animals (p = 0.01) showed a curative
      effect after the observation period. We concluded that SPZ had the best in vitro
      and in vivo activity against F. pedrosoi.

PMID- 9283667
TI  - Temperature requirements of Chrysomya albiceps (Wiedemann, 1819) (Diptera,
      Calliphoridae) under laboratory conditions.
AB  - Chrysomya albiceps specimens were obtained from colonies established with larvae
      and adults collected at the Federal Rural University in Rio de Janeiro,
      Seropedica, State of Rio de Janeiro. The larval stage of C. albiceps was allowed
      to develop in climatic chambers at temperatures of 18, 22, 27 and 32 degrees C,
      and the pupal stage was allowed to develop at 22, 27 and 32 degrees C (60 +/- 10%
      RH and 14 hr photoperiod). The duration and viability of the larval stage of C.
      albiceps at 18, 22, 27 and 32 degrees C were 21.30, 10.61, 5.0 and 4.0 days and
      76.5, 88.5, 98.5 and 99.5%, respectively, with mean mature larval weights of
      45.16, 81.86, 84.35 and 70.53 mg, respectively. Mean duration and viability of
      the pupal stage at 22, 27 and 32 degrees C were 9.36, 4.7 and 3.0 days and 93.8,
      100 and 100%, respectively. The basal temperature for the larval and pupal stage
      and for the larval and adult phase were 15.04, 17.39 and 15.38 degrees C,
      corresponding to 65.67, 44.15 and 114.23 DD.

PMID- 9283668
TI  - Agar dilution method for susceptibility testing of Neisseria gonorrhoeae.
AB  - The antibiotic susceptibilities of Neisseria gonorrhoeae isolates obtained from
      patients attending a clinic for sexually transmitted diseases in Tucuman,
      Argentina, were determined by the agar dilution method (MIC). 3.5% of the
      isolates produced beta-lactamase. A total of 96.5% of beta-lactamase negative
      isolates tested were susceptible to penicillin (MIC < or = 2 micrograms/ml-1);
      14.03% of the tested isolates were resistant to tetracycline (MIC < or = 2
      micrograms/ml-1), and 98% of the tested isolates were susceptible to
      spectinomycin (MIC < or = 64 micrograms/ml-1). The MICs for 95% of the isolates,
      tested for other drugs were: < or = 2 micrograms/ml-1 for cefoxitin, < or = 0.06
      microgram/ml-1 for cefotaxime, < or = 0.25 microgram/ml-1 for norfloxacin, < or =
      10 micrograms/ml-1 for cephaloridine, < or = 10 micrograms/ml-1 for cephalexin,
      and < or = 50 micrograms/ml-1 for kanamycin. Antibiotic resistance among N.
      gonorrhoeae isolates from Tucuman, Argentina, appeared to be primarily limited to
      penicillin and tetracycline, which has been a general use against gonorrhoeae in
      Tucuman since 1960. Periodic monitoring of the underlying susceptibility profiles
      of the N. gonorrhoeae strains prevalent in areas of frequent transmission may
      provide clues regarding treatment options and emerging of drug resistance.

PMID- 9283669
TI  - Characterization of subpopulations (clones and subclones) of the 21 SF strain of
      Trypanosoma cruzi after long lasting maintenance in the laboratory.
AB  - Several studies have shown a clonal structure of Trypanosoma cruzi and its
      possible correlation with the behavioral heterogeneity of the parasite strains.
      In the present study, the 21 SF strain, that have been maintained in laboratory
      by successive passages in mice, for more than 15 years, showing a stability of
      biological and isoenzymic characteristics has been cloned, with the objective of
      establishing the characters of its clones and subclones. With the technique of
      isolation of a single parasite from the blood of infected mice, 5 clones and 14
      subclones have been obtained. After four passages into mice, inoculum of 10(5)
      was obtained for each clone and subclone and inoculated into mice weighing 10 to
      12 g. These were used for the study of the biological behavior of the clones:
      evolution of parasitemia, morphology of blood forms and host mortality. For
      isoenzymic characterization, the clones and subclones were analyzed for ALAT,
      ASAT, GPI and PGM enzymes. Results have shown that the 5 clones and the 14
      subclones disclosed a biological behavior similar to the parental strain, with
      minor variability of the parasitemic profiles and also the same isoenzymic
      patterns. These results confirm the stability of the 21 SF strain and indicate a
      clonal homogeneity of its populations. This is compatible with the hypothesis
      that the T. cruzi strains represent an equilibrium of either homogenous or
      heterogeneous populations.

PMID- 9283670
TI  - Comfort and bleeding after percutaneous transluminal coronary angioplasty:
      comparison of a flexible sheath and a standard sheath.
AB  - BACKGROUND: Patients often have discomfort, especially back pain, after
      percutaneous transluminal coronary angioplasty because they must stay relatively
      flat while the sheath remains in the femoral vessel after the procedure. Flexible
      sheaths are now available, allowing the head of the bed to be raised to 60
      degrees during this period of bed rest. OBJECTIVE: We assessed comfort and the
      frequency of bleeding in patients who had undergone percutaneous transluminal
      coronary angioplasty and compared the findings between patients with a flexible
      sheath and patients with a standard sheath. METHODS: Patients were randomly
      assigned either a flexible sheath or a standard sheath during percutaneous
      transluminal coronary angioplasty. Patients' comfort was assessed by
      administering a comfort questionnaire at two intervals after the procedure, and
      the frequency of bleeding was determined by reviewing the patients' charts.
      RESULTS: One hundred seven patients completed the questionnaire. The patients
      with a flexible sheath showed a significantly higher level of comfort than the
      patients with a standard sheath 5 hours after the procedure. Patients with a
      flexible sheath also received less pain medication than did patients with a
      standard sheath. The frequency of bleeding was comparable in both groups.
      CONCLUSIONS: Results of this study support the use of a flexible sheath to
      increase patients' comfort after percutaneous transluminal coronary angioplasty
      without increasing the frequency of bleeding.

PMID- 9283671
TI  - Six-minute walk test and heart rate variability: lack of association in advanced
      stages of heart failure.
AB  - BACKGROUND: The 6-minute walk and heart rate variability have been used to assess
      mortality risk in patients with heart failure, but their relationship to each
      other and their usefulness for predicting mortality at 1 year are unknown.
      OBJECTIVE: To assess the relationships between the 6-minute walk test, heart rate
      variability, and 1-year mortality. METHOD: A sample of 113 patients in advanced
      stages of heart failure (New York Heart Association Functional Class III-IV, left
      ventricular ejection < 0.25) were studied. All 6-minute walks took place in an
      enclosed, level, measured corridor and were supervised by the same nurse. Heart
      rate variability was measured by using (1) a standard-deviation method and (2)
      Poincare plots. Data on RR intervals obtained by using 24-hour Holter monitoring
      were analyzed. Survival was determined at 1 year after the Holter recording.
      RESULTS: The results showed no significant associations between the results of
      the 6-minute walk and the two measures of heart rate variability. The results of
      the walk were related to 1-year mortality but not to the risk of sudden death.
      Both measures of heart rate variability had significant associations with 1-year
      mortality and with sudden death. However, only heart rate variability measured by
      using Poincare plots was a predictor of total mortality and risk of sudden death,
      independent of left ventricular ejection fraction, serum levels of sodium,
      results of the 6-minute walk test, and the standard-deviation measure of heart
      rate variability. CONCLUSIONS: Results of the 6-minute walk have poor association
      with mortality and the two measures of heart rate variability in patients with
      advanced-stage heart failure and a low ejection fraction. Further studies are
      needed to determine the optimal clinical usefulness of the 6-minute walk and
      heart rate variability in patients with advanced-stage heart failure.

PMID- 9283672
TI  - Outpatient use of left ventricular assist devices: nursing, technical, and
      educational considerations.
AB  - Improvements in technology and in the selection, care, and treatment of patients
      have led to wider clinical use of mechanical circulatory support. Considerable
      progress has been made with the use of left ventricular assist devices. Patients
      are currently maintained in outpatient facilities until a donor heart becomes
      available; recently, left ventricular assist devices have started to be used as
      permanent implants. This article outlines the steps that are taken to prepare the
      patient, the patient's family, and the medical staff for discharge from the
      hospital of a patient supported with a left ventricular assist device. Extensive
      technical and clinical training of the primary caregiver and the patient is
      required to prepare for discharge from the hospital. Data are rapidly
      accumulating that show that left ventricular assist devices are safe and
      efficacious for outpatient use. Similar success is expected in clinical trials of
      permanent left ventricular assist devices, suggesting that many more patients
      will benefit from this technology in the future.

PMID- 9283673
TI  - Mucormycosis in diabetes.
AB  - Mucormycosis is a rare opportunistic infection caused by ubiquitous fungi
      typically found in soil, spoiled foods, bread, and dust. The acute infection most
      commonly is rhinocerebral and is associated with metabolic acidosis. Mucormycosis
      spreads quickly and can progress from the paranasal area to the brain in a few
      days. In the case presented, a young diabetic woman had diabetic ketoacidosis and
      classic signs and symptoms of mucormycosis. Even after aggressive and appropriate
      treatment with surgical debridement and IV administration of amphotericin B, the
      fungus invaded the central nervous system. This article discusses current methods
      of treating mucormycosis and important critical care nursing considerations for
      patients who have the infection.

PMID- 9283674
TI  - Malignant hyperthermia.
AB  - Malignant hyperthermia is a pharmacogenetic disease of skeletal muscle
      characterized by hypermetabolism that occurs on exposure to a triggering agent or
      agents. The most common agents are halogenated inhalational anesthetics and
      succinylcholine, a depolarizing muscle relaxant. Patients who experience
      malignant hyperthermia are generally transferred to the ICU for ongoing treatment
      and monitoring for secondary complications of the disorder. Critical care
      practitioners must be both knowledgeable and competent to prevent and treat
      perioperative episodes of malignant hyperthermia. A thorough preoperative
      interview should be done to determine risk factors and susceptible patients. This
      article provides critical care nurses with sound information on the
      pathophysiology of malignant hyperthermia, the ability to assess the disease
      properly and treat the patient both before and after the crisis, and the ability
      to provide support and teaching to patients and patients' families to prevent the
      recurrence of malignant hyperthermia.

PMID- 9283675
TI  - A comparison of transparent polyurethane and dry gauze dressings for peripheral
      i.v. catheter sites: rates of phlebitis, infiltration, and dislodgment by
      patients.
AB  - BACKGROUND: Before a meta-analysis by Hoffman et al was published, polyurethane
      dressings were used at insertion sites for peripheral i.v. catheters at our
      institution. On the basis of the results of the meta-analysis, we began to use
      gauze dressings. The change from polyurethane dressings to gauze dressings
      limited direct observation of the i.v. insertion site, and i.v. catheters were
      anecdotally reported not to be anchored as securely as before. OBJECTIVES: The
      purpose of this study was to compare the effects of the use of transparent
      polyurethane dressings and gauze dressings at insertion sites for peripheral i.v.
      catheters on the frequency of phlebitis, infiltration, and catheter dislodgment
      by patients. METHODS: Two hundred twenty-nine patients were randomized to receive
      either gauze (n = 121) or transparent polyurethane (n = 108) dressings, and
      observations were recorded. RESULTS: The frequency of catheter dislodgment by the
      patient was significantly higher (P < .05) in patients with the gauze dressing
      (15%) than in patients with the transparent polyurethane dressing (6%). A trend
      toward lower frequencies of phlebitis (1.8% vs 3.3%) and infiltration (17.6% vs
      20.7%) was noted in the patients with the transparent polyurethane dressings.
      DISCUSSION: The clinical advantages of the transparent polyurethane dressings lie
      in the ease of direct visualization of the i.v. insertion site and the securement
      of the i.v. catheter. CONCLUSION: At our institution, given the decreased
      disruption of the i.v. therapy with the transparent polyurethane dressings and
      the lack of differences in the rates of phlebitis or infiltration with the two
      types of dressings, we prefer to use transparent polyurethane rather than gauze
      dressings at insertion sites for peripheral i.v. catheters.

PMID- 9283676
TI  - Administration of medications through enteral feeding catheters.
AB  - BACKGROUND: Enteral feeding catheters are commonly used to administer both
      nutritional feedings and oral forms of medications. Obstruction of the catheters
      is a major concern. OBJECTIVES: To study characteristics of obstruction of
      enteral feeding catheters in ICU patients and current knowledge and practices of
      ICU nurses of administering medications through such catheters. METHODS: A
      postcard invitation to participate in this descriptive survey was mailed to a
      random sample of 12,069 members of the American Association of Critical-Care
      Nurses. The 52-item investigator-designed questionnaire was mailed to the 1700
      critical care nurses who agreed to participate; 1167 (68.6%) returned completed
      survey questionnaires. RESULTS: Nurses estimated that 33.8% of their patients
      received 8.9 doses of medication per day through the enteral feeding catheter.
      The rate of obstruction of the tube by medications was 15.6%. Crushed medications
      contributed to obstruction, although liquid forms of the medications often were
      available. Nurses' primary source of knowledge about administering medications
      through enteral feeding catheters was clinical practice (56.9%) and consultation
      with peers (21.7%); only 19% had had inservice training on the topic. Written
      agency guidelines varied considerably, and 74% of nurses used two or more
      techniques that were contrary to recommendations. Factors significantly
      associated with lower rates of obstruction of enteral feeding catheters included
      (1) assistance from the pharmacy service to ensure liquid forms of medications,
      (2) nurses' attendance at a relevant seminar or inservice training program, and
      (3) not routinely crushing and administering enteric-coated or sustained-release
      medications through the enteral feeding catheter. CONCLUSIONS: Collaboration
      between nursing and pharmacy services to ensure delivery of liquid medications
      and avoid use of crushed medications may reduce the high rate of catheter
      obstruction due to medications. Research-based guidelines and a more formal
      dissemination of information to nurses are needed.

PMID- 9283677
TI  - Nurse-physician collaboration and satisfaction with the decision-making process
      in three critical care units.
AB  - OBJECTIVE: To assess and compare levels of nurse-physician collaboration and
      satisfaction with the decision-making process as reported by critical care
      nurses, resident physicians (residents), and attending physicians (attendings) in
      making decisions to transfer individual patients out of the critical care unit,
      and to assess if satisfaction predicts nurse retention. DESIGN: Longitudinal
      descriptive correlational study using self-reporting instruments. SETTINGS: A
      university hospital's surgical ICU, a community teaching hospital's medical ICU,
      and a community hospital's mixed ICU. SUBJECTS: Eighty-one nurses, 23 residents,
      and 37 attendings from the surgical ICU; 44 nurses and 51 residents from the
      medical ICU; 25 nurses and 45 attendings from the community hospital's ICU,
      reporting on the transfers of 473, 465, and 494 patients, respectively. MAIN
      OUTCOME MEASURES: Healthcare providers' reported levels of collaboration and
      satisfaction with the decision-making process, the correlations between
      collaboration and satisfaction, and nurse retention. RESULTS: Nurses and
      physicians within sites (except attendings from the surgical ICU) reported
      similarly moderate amounts of collaboration, but nurses reported less
      satisfaction with decision making than did physicians in all sites. Collaboration
      was related to satisfaction with decision making for all providers, but more
      strongly for nurses. The strength of the relationship for nurses was similar in
      all sites. Nurses' satisfaction with decision making did not predict their
      retention. CONCLUSIONS: Collaboration between nurses and physicians is a more
      important component of satisfaction with decision making for nurses than for
      physicians. Any interventions to change the amount of collaboration in practice
      must take account of this difference.

PMID- 9283678
TI  - The impact of do-not-resuscitate orders on nursing workload in an ICU.
AB  - BACKGROUND: The meaning of do-not-resuscitate orders and their impact on nursing
      care have been a source of confusion, and the results of the few studies that
      have examined nursing care of ICU patients with these orders have been
      conflicting. OBJECTIVES: To assess nursing workload associated with caring for
      patients with do-not-resuscitate orders and to better understand the patients and
      selected events associated with these orders. METHOD: Sixty patients from
      medical, surgical, and neuroscience ICUs met the criteria for the study. The
      Medicus Systems Corporation InterAct 2000 Workload and Productivity System was
      used to classify patients by type; the results reflected the number of hours of
      nursing care required per 24 hours. Data on patient type for 1 day before and 1
      day after do-not-resuscitate orders were written were available for 31 of the 60
      patients. These data were analyzed. RESULTS: The number of hours of nursing care
      required 1 day before and 1 day after a do-not-resuscitate order did not change.
      The amount of nursing care remained the same or increased for 74% (23/31) of the
      patients after the order was written. Patients were classified as types IV (n =
      8), V (n = 20), and VI (n = 3) after the order was written. CONCLUSIONS: A high
      level of nursing care was required for this group of critically ill patients, and
      the do-not-resuscitate order did not alter the number of hours of nursing care
      required after the order was written.

PMID- 9283680
TI  - Efficacy of preoperative ICU tours for prospective coronary artery bypass
      patients.

PMID- 9283679
TI  - Harnessing the platelet.
AB  - Appreciation of the critical role of platelets in cardiovascular disease came
      when it was shown that aspirin, by virtue of its ability to block platelet
      aggregation, reduced the combined incidence of MI, stroke, and vascular death by
      25%. Understanding the key role played by platelets in acute thrombotic vascular
      events prompted the development of a new class of drugs to control platelet
      action. Platelet aggregation is mediated exclusively by the platelet fibrinogen
      receptor GP IIb/IIIa. The binding of the receptor with fibrinogen is the final
      common pathway leading to platelet aggregation and thrombus formation. Abciximab,
      the first GP IIb/IIIa platelet receptor inhibitor, effectively reduces the
      thrombotic complications in acute coronary vascular events. The newer GP IIb/IIIa
      inhibitors, the synthetic peptide antagonists, have been shown to be more
      specific, to be nonimmunogenic, and to cause less bleeding. It is predictable
      that an oral GP IIb/IIIa inhibitor will become part of the standard repertoire in
      patients with unstable angina. The platelet has taken center stage in the battle
      against arterial thrombosis. The direction of our medical attack on acute
      coronary events is clear: harness the platelet.

PMID- 9283681
TI  - Evidence for the involvement of P2-purinoceptors in the cholinergic contraction
      of the guinea-pig ileum.
AB  - In the isolated ileum of the guinea-pig the P2-purinoceptor antagonists PPADS and
      suramin: (a) strongly inhibited the cholinergic contractile effect of alpha,beta
      methylene ATP, (b) did not influence contractions evoked by exogenous
      acetylcholine (ACh) but, (c) moderately (by about 30%) inhibited cholinergic
      contractions due to electrical field stimulation (EFS), in a non-additive manner.
      These results suggest that an endogenous ligand that stimulates P2-purinoceptors
      (possibly ATP) is involved in the contractile effect of EFS, as a positive
      modulator of ACh release.

PMID- 9283682
TI  - Evidence that anandamide and EDHF act via different mechanisms in rat isolated
      mesenteric arteries.
AB  - The endogenous cannabinoid, anandamide, has been suggested as an endothelium
      derived hyperpolarizing factor (EDHF). We found that anandamide-evoked relaxation
      in isolated segments of rat mesenteric artery was associated with smooth muscle
      hyperpolarization. However, although anandamide-evoked relaxation was inhibited
      by either charybdotoxin (ChTX) or iberiotoxin, inhibition of the relaxation to
      EDHF required a combination of ChTX and apamin. The relaxations induced by either
      anandamide or EDHF were not inhibited by the cannabinoid receptor (CB1)
      antagonist SRI41716A, or mimicked by selective CB1 agonists. Thus, anandamide
      appears to cause smooth muscle relaxation via a CB1 receptor-independent
      mechanism and cannabinoid receptor activation apparently does not contribute to
      EDHF-mediated relaxation in this resistance artery.

PMID- 9283683
TI  - Gabapentin (neurontin) and S-(+)-3-isobutylgaba represent a novel class of
      selective antihyperalgesic agents.
AB  - 1. Gabapentin (neurontin) is a novel antiepileptic agent that binds to the alpha
      2 delta subunit of voltage-dependent calcium channels. The only other compound
      known to possess affinity for this recognition site is the (S)-(+)-enantiomer of
      3-isobutylgaba. However, the corresponding (R)-(-)-enantiomer is 10 fold weaker.
      The present study evaluates the activity of gabapentin and the two enantiomers of
      3-isobutylgaba in formalin and carrageenan-induced inflammatory pain models. 2.
      In the rat formalin test, S-(+)-3-isobutylgaba (1-100 mg kg-1) and gabapentin (10
      300 mg kg-1) dose-dependently inhibited the late phase of the nociceptive
      response with respective minimum effective doses (MED) of 10 and 30 mg kg-1, s.c.
      This antihyperalgesic action of gabapentin was insensitive to naloxone (0.1-10.0
      mg kg-1, s.c.). In contrast, the R-(-)-enantiomer of 3-isobutylgaba (1-100 mg kg
      1) produced a modest inhibition of the late phase at the highest dose of 100 mg
      kg-1. However, none of the compounds showed any effect during the early phase of
      the response. 3. The s.c. administration of either S-(+)-3-isobutylgaba (1-30 mg
      kg-1) or gabapentin (10-100 mg kg-1), after the development of peak carrageenan
      induced thermal hyperalgesia, dose-dependently antagonized the maintenance of
      this response with MED of 3 and 30 mg kg-1, respectively. Similar administration
      of the two compounds also blocked maintenance of carrageenan-induced mechanical
      hyperalgesia with MED of 3 and 10 mg kg-1, respectively. In contrast, R-(-)-3
      isobutylgaba failed to show any effect in the two hyperalgesia models. 4. The
      intrathecal administration of gabapentin dose-dependently (1-100
      micrograms/animal) blocked carrageenan-induced mechanical hyperalgesia. In
      contrast, administration of similar doses of gabapentin into the inflamed paw was
      ineffective at blocking this response. 5. Unlike morphine, the repeated
      administration of gabapentin (100 mg kg-1 at start and culminating to 400 mg kg
      1) over 6 days did not lead to the induction of tolerance to its antihyperalgesic
      action in the formalin test. Furthermore, the morphine tolerance did not cross
      generalize to gabapentin. The s.c. administration of gabapentin (10-300 mg kg-1),
      R-(-) (3-100 mg kg-1) or S-(+)-3-isobutylgaba (3-100 mg kg-1) failed to inhibit
      gastrointestinal motility, as measured by the charcoal meal test in the rat.
      Moreover, the three compounds (1-100 mg kg-1, s.c.) did not generalize to the
      morphine discriminative stimulus. Gabapentin (30-300 mg kg-1) and S-(+)
      isobutylgaba (1-100 mg kg-1) showed sedative/ataxic properties only at the
      highest dose tested in the rota-rod apparatus. 6. Gabapentin (30-300 mg kg-1,
      s.c.) failed to show an antinociceptive action in transient pain models. It is
      concluded that gabapentin represents a novel class of antihyperalgesic agents.

PMID- 9283684
TI  - Effects of beta 2-agonist- and dexamethasone-treatment on relaxation and
      regulation of beta-adrenoceptors in human bronchi and lung tissue.
AB  - 1. Long-term treatment with beta 2-adrenoceptor agonists can lead to a decreased
      therapeutic efficacy of bronchodilatation in patients with obstructive pulmonary
      disease. In order to examine whether or not this is due to beta-adrenoceptor
      desensitization, human bronchial muscle relaxation was studied in isolated
      bronchial rings after pretreatment with beta 2-adrenoceptor agonists.
      Additionally, the influence of pretreatment with dexamethasone on desensitization
      was studied. 2. The effect of beta 2-agonist incubation alone and after
      coincubation with dexamethasone on density and affinity of beta-adrenoceptors was
      investigated by radioligand binding experiments. 3. In human isolated bronchi,
      isoprenaline induces a time- and concentration-dependent beta-adrenoceptor
      desensitization as judged from maximal reduction in potency by a factor of 7 and
      reduction of 73 +/- 4% in efficacy of isoprenaline to relax human bronchial
      smooth muscle. 4. After an incubation period of 60 min with 100 mumol l-1
      terbutaline, a significant decline in its relaxing efficacy (81 +/- 8%) and
      potency (by a factor 5.5) occurred. 5. Incubation with 30 mumol l-1 isoprenaline
      for 60 min did not impair the maximal effect of a subsequent aminophylline
      response but led to an increase in potency (factor 4.4). 6. Coincubation of
      dexamethasone with isoprenaline (120 min; 30 mumol l-1) preserved the effect of
      isoprenaline on relaxation (129 +/- 15%). 7. In radioligand binding experiments,
      pretreatment of lung tissue for 60 min with isoprenaline (30 mumol l-1) resulted
      in a decrease in beta-adrenoceptor binding sites (Bmax) to 64 +/- 1.6% (P <
      0.05), while the antagonist affinity (KD) for [3H]-CGP-12177 remained unchanged.
      8. In contrast, radioligand binding studies on lung tissue pretreated with either
      dexamethasone (30 mumol l-1) or isoprenaline (30 mumol l-1) plus dexamethasone
      (30 mumol l-1) for 120 min did not lead to a significant change of Bmax (160 +/-
      22.1% vs 142.3 +/- 28.7%) or KD (5.0 nmol l-1 vs 3.5 nmol l-1) compared to the
      controls. 9. In conclusion, pretreatment of human bronchi with beta-adrenoceptor
      agonists leads to functional desensitization and, in lung tissue, to down
      regulation of beta-adrenoceptors. This effect can be counteracted by additional
      administration of dexamethasone. Our model of desensitization has proved useful
      for the identification of mechanisms of beta-adrenoceptor desensitization and
      could be relevant for the evaluation of therapeutic strategies to counteract
      undesirable effects of long-term beta-adrenoceptor stimulation.

PMID- 9283685
TI  - Effects of Ca2+ channel blocker neurotoxins on transmitter release and
      presynaptic currents at the mouse neuromuscular junction.
AB  - 1. The effects of the voltage-dependent calcium channel (VDCC) blockers omega
      agatoxin IVA (omega-AgaIVA), omega-conotoxin GVIA (omega-CgTx), omega-conotoxin
      MVIIC (omega-MVIIC) and omega-conotoxin MVIID (omega-MVIID) were evaluated on
      transmitter release in the mouse diaphragm preparation. The effects of omega
      AgaIVA and omega-MVIIC were also evaluated on the perineurial calcium and calcium
      dependent potassium currents, ICa and IK(Ca), respectively, in the mouse levator
      auris preparation. 2. The P- and Q-type VDCC blocker omega-AgaIVA (100 nM) and P-
      Q- and N-type channel blockers omega-MVIIC (1 microM) and omega-MVIID (3 microM)
      strongly reduced transmitter release (> 80-90% blockade) whereas the selective N
      type channel blocker omega-CgTx (5 microM) was ineffective. 3. The process of
      release was much more sensitive to omega-MVIIC (IC50 = 39 nM) than to omega-MVIID
      (IC50 = 1.4 microM). After almost completely blocking transmitter release
      (quantal content approximately 0.3% of its control value) with 3 microM omega
      MVIIC, elevating the external [Ca2+] from 2 to 10 mM induced an increase of
      approximately 20 fold on the quantal content of the endplate potential (e.p.p.)
      (from 0.2 +/- 0.04 to 4.8 +/- 1.4). 4. Nerve-evoked transmitter release in a low
      Ca(2+)-high Mg2+ medium (low release probability, quantal content = 2 +/- 0.1)
      had the same sensitivity to omega-AgaIVA (IC50 = 16.8 nM) as that in normal
      saline solutions. In addition, K(+)-evoked transmitter release was also highly
      sensitive to the action of this toxin (IC50 = 11.5 nM; 100 nM > 95% blockade).
      The action of omega-AgaIVA on transmitter release could be reversed by toxin
      washout if the experiments were carried out at 31-33 degrees C. Conversely, the
      effect of omega-AgaIVA persisted even after two hours of toxin washout at room
      temperature. 5. Both the calcium and calcium-dependent potassium presynaptic
      currents, ICa and IK(Ca), respectively, were highly sensitive to low
      concentrations (10-30 nM) of omega-AgaIVA. The ICa and the IK(Ca) were also
      strongly reduced by 1 microM omega-MVIIC. The most marked difference between the
      action of these two toxins was the long incubation times required to achieve
      maximal effects with omega-MVIIC. 6. In summary these results provide more
      evidence that synaptic transmission at the mammalian neuromuscular junction is
      mediated by Ca2+ entry through P- and/or Q-type calcium channels.

PMID- 9283686
TI  - Influence of metabotropic glutamate receptor agonists on the inhibitory effects
      of adenosine A1 receptor activation in the rat hippocampus.
AB  - 1. Glutamate and other amino acids are the main excitatory neurotransmitters in
      many brain regions, including the hippocampus, by activating ion channel-coupled
      glutamate receptors, as well as metabotropic receptors linked to G proteins and
      second messenger systems. Several conditions which promote the release of
      glutamate, like frequency stimulation and hypoxia, also lead to an increase in
      the extracellular levels of the important neuromodulator, adenosine. We studied
      whether the activation of different subgroups of metabotropic glutamate receptors
      (mGluR) could modify the known inhibitory effects of a selective adenosine A1
      receptor agonist on synaptic transmission in the hippocampus. The experiments
      were performed on hippocampal slices taken from young (12-14 days old) rats.
      Stimulation was delivered to the Schaffer collateral/commissural fibres, and
      evoked field excitatory postsynaptic potentials (fe. p.s.p.) recorded
      extracellularly from the stratum radiatum in the CAI area. 2. The concentration
      response curve for the inhibitory effects of the selective adenosine A1 receptor
      agonist, N6-cyclopentyladenosine (CPA; 2-50 nM), on the fe.p.s.p. slope (EC50 =
      12.5 (9.2-17.3; 95% confidence intervals)) was displaced to the right by the
      group I mGluR selective agonist, (R,S)-3,5-dihydroxyphenylglycine (DPHG; 10
      microM) (EC50 = 27.2 (21.4-34.5) nM, n = 4). The attenuation of the inhibitory
      effect of CPA (10 nM) on the fe.p.s.p. slope by DHPG (10 microM) was blocked in
      the presence of the mGluR antagonist (which blocks group I and II mGluR), (R,S)
      alpha-methyl-4-carboxyphenylglycine (MCPG; 500 microM). DHPG (10 microM) itself
      had an inhibitory effect of 20.1 +/- 1.9% (n = 4) on the fe.p.s.p. slope. 3. The
      concentration-response curves for the inhibitory effects of CPA (2-20 nM) on the
      fe.p.s.p. slope were not modified either in the presence of the group II mGluR
      selective agonist, (2S,3S,4S)-alpha-(carboxycyclopropyl)glycine (L-CCG-I; 1
      microM), or in the presence of the non-selective mGluR agonist (which activates
      both group I and II mGluR), (IS,3R)-1-aminocyclopentyl-1,3-dicarboxylate (ACPD;
      100 microM). L-CCG-I had no consistent effects and ACPD (100 microM) decreased by
      19.4 +/- 1.8% (n = 4) the fe.p.s.p. slope. 4. The concentration-response curve
      for the inhibitory effects of CPA (2-100 nM) on the fe.p.s.p. slope (EC50 = 8.2
      (6.9-9.6) nM) was displaced to the right by the group III mGluR selective
      agonist, L-2-amino-4-phosphonobutyrate (L-AP4; 25 microM) (EC50 = 17.7 (13.1
      21.9) nM, n = 4). The attenuation of the inhibitory effect of CPA (10 nM) on the
      fe.p.s.p. slope by L-AP4 (25 microM) was blocked in the presence of the mGluR
      antagonist (selective for the group III mGluR), (R,S)-alpha-methyl-4
      phosphonophenylglycine (MPPG; 200 microM). 5. Both the direct effect of DHPG on
      synaptic transmission and the attenuation of the inhibitory effect of CPA (10 nM)
      were prevented in the presence of the protein kinase C selective inhibitors,
      staurosporine (1 microM) or chelerythrine (5 microM), and thus attributed to
      activation of protein kinase C. 6. The attenuation by L-AP4 (25 microM) of the
      inhibitory effect of CPA (10 nM) on the fe.p.s.p. slope was also prevented by the
      protein kinase C selective inhibitors, staurosporine (1 microM) or chelerythrine
      (5 microM), and thus attributed to activation of protein kinase C. But this
      effect seemed to be distinct from the direct effect of L-AP4 (25 microM) on
      synaptic transmission, which was not modified by the protein kinase C selective
      inhibitors. 7. We conclude that agonists of metabotropic glutamate receptors
      (Groups I and III) are able to attenuate the inhibitory effects of adenosine A1
      receptor activation in the hippocampus. This interaction may have
      pathophysiological relevance in hypoxia, in which there is marked release of both
      excitatory amino acids and the important endogenous neuroprotective substance,
      adenosine.

PMID- 9283687
TI  - Contribution of phosphodiesterase isozymes to the regulation of the L-type
      calcium current in human cardiac myocytes.
AB  - 1. To determine the contribution of the various phosphodiesterase (PDE) isozymes
      to the regulation of the L-type calcium current (ICa(L)) in the human myocardium,
      we investigated the effect of selective and non-selective PDE inhibitors on
      ICa(L) in single human atrial cells by use of the whole-cell patch-clamp method.
      We repeated some experiments in rabbit atrial myocytes, to make a species
      comparison. 2. In human atrial cells, 100 microM pimobendan increased ICa(L)
      (evoked by depolarization to +10 mV from a holding potential of -40 mV) by 250.4
      +/- 45.0% (n = 15), with the concentration for half-maximal stimulation (EC50)
      being 1.13 microM. ICa(L) was increased by 100 microM UD-CG 212 by 174.5 +/-
      30.2% (n = 10) with an EC50 value of 1.78 microM in human atrial cells. These two
      agents inhibit PDE III selectively. 3. A selective PDE IV inhibitor, rolipram (1
      100 microM), did not itself affect ICa(L) in human atrial cells. However, 100
      microM rolipram significantly enhanced the effect of 100 microM UD-CG 212 on
      ICa(L) (increase with UD-CG 212 alone, 167.9 +/- 33.9, n = 5; increase with the
      two agents together, 270.0 +/- 52.2%; n = 5, P < 0.05). Rolipram also enhanced
      isoprenaline (5 nM)-stimulated ICa(L) by 52.9 +/- 9.3% (n = 5) in human atrial
      cells. 4. In rabbit atrial cells, ICa(L) at +10 mV was increased by 22.1 +/- 9.0%
      by UD-CG 212 (n = 10) and by 67.4 +/- 12.0% (n = 10) by pimobendan (each at 100
      microM). These values were significantly lower than those obtained in human
      atrial cells (P < 0.0001). Rolipram (1-100 microM) did not itself affect ICa(L)
      in rabbit atrial cells. However, ICa(L) was increased by 215.7 +/- 65.2% (n = 10)
      by the combination of 100 microM UD-CG 212 and 100 microM rolipram. This value
      was almost 10 times larger than that obtained for the effect of 100 microM UD-CG
      212 alone. 5. These results imply a species difference: in the human atrium, the
      PDE III isoform seems dominant, whereas PDE IV may be more important in the
      rabbit atrium for regulating ICa(L). However, PDE IV might contribute
      significantly to the regulation of intracellular cyclic AMP in human myocardium
      when PDE III is already inhibited or when the myocardium is under beta
      adrenoceptor-mediated stimulation.

PMID- 9283689
TI  - Fluoroquinolone (ciprofloxacin) secretion by human intestinal epithelial (Caco-2)
      cells.
AB  - 1. Human intestinal epithelial Caco-2 cells were used to investigate the
      mechanistic basis of transepithelial secretion of the fluoroquinolone antibiotic
      ciprofloxacin. 2. Net secretion and cellular uptake of ciprofloxacin (at 0.1 mM)
      were not subject to competitive inhibition by sulphate, thiosulphate, oxalate,
      succinate and para-amino hippurate, probenecid (10 mM), taurocholate (100 microM)
      or bromosulphophthalein (100 microM). Similarly tetraethylammonium and N
      'methylnicotinamide (10 mM) were without effect. 3. Net secretion of
      ciprofloxacin was inhibited by the organic exchange inhibitor 4,4'
      diisothiocyanostilbene-2-2'-disulphonic acid (DIDS, 400 microM). 4. Net secretion
      of ciprofloxacin was partially inhibited by 100 microM verapamil, whilst net
      secretion of the P-glycoprotein substrate vinblastine was totally abolished under
      these conditions. Ciprofloxacin secretion was unaltered after preincubation of
      cells with two anti-P-glycoprotein antibodies (UIC2 and MRK16), which both
      significantly reduced secretory vinblastine flux (measured in the same cell
      batch). Ciprofloxacin (3 mM) failed to inhibit vinblastine net secretin in Caco-2
      epithelia, and was not itself secreted by the P-glycoprotein expressing and
      vinblastine secreting dog kidney cell line, MDCK. 5. Net secretion and cellular
      uptake of ciprofloxacin (at 0.1 mM) were not subject to alterations of either
      cytosolic or medium pH, or dependent on the presence of medium Na+, Cl- or K+ in
      the bathing media. 6. The substrate specificity of the ciprofloxacin secretory
      transport in Caco-2 epithelia is distinct from both the renal organic anion and
      cation transport. A role for P-glycoprotein in ciprofloxacin secretion may also
      be excluded. A novel transport mechanism, sensitive to both DIDS and verapamil
      mediates secretion of ciprofloxacin by human intestinal Caco-2 epithelia.

PMID- 9283688
TI  - Inhibition by cannabinoid receptor agonists of acetylcholine release from the
      guinea-pig myenteric plexus.
AB  - 1. The dose-related inhibition of the twitch responses of the myenteric plexus
      longitudinal muscle preparation of the guinea-pig small intestine by cannabinoid
      (CB) agonists, (+)-WIN 55212 and CP 55940 during stimulation at 0.1 Hz with
      supramaximal voltage was confirmed. These agonists inhibited acetylcholine (ACh)
      release in the presence of physostigmine (7.7 microM) thus indicating a
      prejunctional site of action. 2. Inhibition of twitch responses and ACh release
      by CB agonists was reversed by the CB1-selective cannabinoid receptor antagonist,
      SR141716A. Dose-response curves to (+)-WIN 55212 and CP 55940 were shifted to the
      right, with no reduction of maximal response, by pretreatment with SR141716A
      (31.6-1000 nM), but not its vehicle, Tween 80 (1 microM). However, at very high
      concentrations (25-400 microM), Tween 80 itself caused a dose-related inhibition
      of the twitch response which was significantly reduced in the presence of
      SR141716A (1 microM). The opioid receptor antagonist, naloxone (1 microM) had no
      significant effect on the inhibition by CP 55940 of the twitch response. 3. (+)
      WIN 55212, CP 55940 and Tween 80 (50 microM) had no effect on responses to
      exogenous ACh, confirming that their actions were prejunctional. SR141716A (1
      microM) did not increase the sensitivity of the longitudinal muscle to either ACh
      or histamine, but inhibited the responses to high doses of ACh. 4. The (-)
      enantiomer of WIN 55212, was approximately 300 times less active than the (+)
      enantiomer in inhibiting the twitch response, had no CB1 antagonist activity
      against the active isomer and did not inhibit the release of ACh in the presence
      of physostigmine. 5. The dissociation constant (KD) values for SR 141716A against
      the inhibitory effect of (+)-WIN 55212 and CP 55940 on the twitch response were
      12.07 nM (95% confidence intervals 8.55 and 20.83) and 6.44 nM (95% confidence
      intervals 4.70 and 10.24), respectively. In experiments in which the release of
      ACh was inhibited by (+)-WIN 55212, the KD values were 9.21 nM and 10.53 nM at
      SR141716A concentrations of 31.6 nM and 100 nM, respectively. The KD values for
      the antagonism by naloxone of the inhibition of the twitch responses and the
      inhibition of ACh release by normorphine in this preparation were found to be
      2.38 +/- 0.69 nM and 2.00 +/- 0.9 nM, respectively. 6. During maximal inhibition
      of ACh release by (+)-WIN 55212, the addition of normorphine (400 nM) caused a
      further significant decrease in ACh output. 7. SR141716A alone produced a
      significant increase in ACh release in both the absence and presence of exogenous
      cannabinoid drugs, hence we conclude that it has a presynaptic site of action. We
      also conclude that SR141716A acts either by antagonizing the effect of an
      endogenous CB1 receptor agonist or by having an inverse agonist effect at these
      receptors.

PMID- 9283690
TI  - Activation of microsomal cytochrome P450 mono-oxygenase by Ca2+ store depletion
      and its contribution to Ca2+ entry in porcine aortic endothelial cells.
AB  - 1. We investigated how microsomal cytochrome P450 mono-oxygenase (Cyp450 MO) is
      regulated in cultured porcine aortic endothelial cells. The hypothesis that a
      Cyp450 MO-derived metabolite links Ca2+ store depletion and Ca2+ entry was
      studied further. 2. Microsomal Cyp450 MO was monitored fluorometrically by
      dealkylation of 1-ethoxypyrene-3,6,8-tris-(dimethyl-sulphonamide; EPSA) in
      saponin permeabilized cells or in subcellular compartments. Endothelial Ca2+
      signalling was measured by a standard fura-2 technique, membrane potential was
      determined with the potential-sensitive fluorescence dye, bis-(1,3
      dibutylbarbituric acid) pentamethine oxonol (DiBAC4(5)) and tyrosine kinase was
      quantified by measuring the phosphorylation of a immobilized substrate with a
      horseradish peroxidase labelled phosphotyrosine specific antibody. 3. Depletion
      of cellular Ca2+ pools with inositol 1,4,5-trisphosphate (IP3), thapsigargin or
      cyclopiazonic acid activated microsomal Cyp450 MO. Similar to direct Ca2+ store
      depletion, chelating of intramicrosomal Ca2+ with oxalate stimulated Cyp450 MO
      activity, while changing cytosolic free Ca2+ failed to influence Cyp450 MO
      activity. These data indicate that microsomal Cyp450 MO is activated by depletion
      of IP3-sensitive stores. 4. Besides the common cytochrome P450 inhibitors,
      econazole, proadifen and miconazole, thiopentone sodium and methohexitone
      inhibited Cyp450 MO in a concentration-dependent manner. The physiological
      substrate of Cyp450 MO, arachidonic acid, inhibited EPSA dealkylation. In
      contrast to most other cytochrome P450 inhibitors used in this study, thiopentone
      sodium did not directly interfere with Ca2+ entry pathways, membrane
      hyperpolarization due to K+ channel activation or tyrosine kinase activity. 5.
      Inhibition of Cyp450 MO by thiopentone sodium diminished Ca2+/Mn2+ entry to Ca2+
      store depletion by 43%, while it did not interfere with intracellular Ca2+
      release by IP3 or thapsigargin. 6. Cyp450 MO inhibition with thiopentone sodium
      diminished autacoid-induced membrane hyperpolarization. 7. Induction of Cyp450 MO
      with dexamethasone/clofibrate for 72 h yielded increases in thapsigargin-induced
      Cyp450 MO activity (by 35%), Ca2+/Mn2+ entry (by 105%) and membrane
      hyperpolarization (by 40%). 8. The Cyp450 MO-derived compounds, 11,12 and 5,6
      epoxyeicosatrienoic acids (EETs) yielded membrane hyperpolarization, insensitive
      to thiopentone sodium. 9. These data demonstrate that endothelial Cyp450 MO is
      activated by Ca2+ store depletion and Cyp450 MO produced compounds that
      hyperpolarize endothelial cells. 10. The data presented and our previous findings
      indicate that Cyp450 MO plays a crucial role in the regulation of store-operated
      Ca2+ influx. We propose that Cyp450 MO-derived EETs constitute a signal for Ca2+
      entry activation and increase the driving force for Ca2+ entry by membrane
      hyperpolarization in porcine aortic endothelial cells.

PMID- 9283691
TI  - Evidence that the substance P-induced enhancement of pacemaking in lymphatics of
      the guinea-pig mesentery occurs through endothelial release of thromboxane A2.
AB  - 1. In vitro studies were performed to examine the mechanisms underlying substance
      P-induced enhancement of constriction rate in guinea-pig mesenteric lymphatic
      vessels. 2. Substance P caused an endothelium-dependent increase in lymphatic
      constriction frequency which was first significant at a concentration of 1 nM
      (115 +/- 3% of control, n = 11) with 1 microM, the highest concentration tested,
      increasing the rate to 153 +/- 4% of control (n = 9). 3. Repetitive 5 min
      applications of substance P (1 microM) caused tachyphylaxis with tissue
      responsiveness tending to decrease (by an average of 23%) and significantly
      decreasing (by 72%) for application at intervals of 30 and 10 min, respectively.
      4. The competitive antagonist of tachykinin receptors, spantide (5 microM) and
      the specific NK1 receptor antagonist, WIN51708 (10 microM) both prevented the
      enhancement of constriction rate induced by 1 microM substance P. 5. Endothelial
      cells loaded with the Ca2+ sensing fluophore, fluo 3/AM did not display a
      detectable change in [Ca2+]i upon application of 1 microM substance P. 6.
      Inhibition of nitric oxide synthase by NG nitro-L-arginine (L-NOARG; 100 microM)
      had no significant effect on the response induced by 1 microM substance P. 7. The
      enhancement of constriction rate induced by 1 microM substance P was prevented by
      the cyclooxygenase inhibitor, indomethacin (3 microM), the thromboxane A2
      synthase inhibitor, imidazole (50 microM), and the thromboxane A2 receptor
      antagonist, SQ29548 (0.3 microM). 8. The stable analogue of thromboxane A2,
      U46619 (0.1 microM) significantly increased the constriction rate of lymphangions
      with or without endothelium, an effect which was prevented by SQ29548 (0.3
      microM). 9. Treatment with pertussis toxin (PTx; 100 ng ml-1) completely
      abolished the response to 1 microM substance P without inhibiting either the
      perfusion-induced constriction or the U46619-induced enhancement of constriction
      rate. 10. Application of the phospholipase A2 inhibitor, antiflammin-1 (1 nM)
      prevented the enhancement of lymphatic pumping induced by substance P (1 microM),
      without inhibiting the response to either U46619 (0.1 microM) or acetylcholine
      (10 microM). 11. The data support the hypothesis that the substance P-induced
      increase in pumping rate is mediated via the endothelium through NK1 receptors
      coupled by a PTx sensitive G-protein to phospholipase A2 and resulting in
      generation of the arachidonic acid metabolite, thromboxane A2 this serving as the
      diffusible activator.

PMID- 9283692
TI  - Hypoglycaemic effects of the novel antidiabetic agent repaglinide in rats and
      dogs.
AB  - 1. Repaglinide, a novel compound with a nonsulphonylurea structure, is currently
      being clinically tested as a therapeutic agent. In the present study, the
      hypoglycaemic effects of repaglinide in rats and dogs were investigated. 2.
      Whereas the R-enantiomer, AG-EE 624 ZW, showed only weak hypoglycaemic activity,
      the S-enantiomer, repaglinide, turned out to be a potent hypoglycaemic compound
      in rats after oral as well as after intravenous administration. Only 50% of the
      dose of repaglinide was needed to be equieffective with the racemic mixture AG-EE
      388 ZW. The corresponding ED50 values calculated for the effects after 120 min
      p.a. (intravenous administration) were 3.4 micrograms kg-1 (repaglinide) and 6
      micrograms kg-1 (AG-EE 388 ZW). 3. When compared to glimepiride or glibenclamide,
      repaglinide displayed a 18 to 25 times higher potency in fasted rats. The ED50
      values calculated for the effects after 120 min p.a. (oral administration) were
      10 micrograms kg-1 (repaglinide), 182 micrograms kg-1 (glimepiride) and 255
      micrograms kg-1 (glibenclamide). 4. In glucose loaded rats (0.5, 1.0, 2.0 and 3.0
      g kg-1 glucose, p.o.) repaglinide exerted a very strong antihyperglycaemic
      activity which was even more pronounced than under normoglycaemic conditions. So
      for a reduction in blood glucose of 1 mmol l-1, 10.3, 9.3, 7.0 8.4 and 7.2
      micrograms kg-1 repaglinide were needed after glucose loads of 0.0, 0.5, 1.0, 2.0
      and 3.0 g kg-1, respectively. 5. In beagle dogs repaglinide again showed a
      pronounced hypoglycaemic effect (ED50 28.3 micrograms kg-1) which lasted for up
      to 24 h. However, insulin levels were only transiently increased. 6. The in vivo
      data presented are well supported by recently published in vitro findings. From
      its activity profile, repaglinide appears to be a promising new therapeutic
      agent.

PMID- 9283694
TI  - Investigation of the mechanisms underlying the hypophagic effects of the 5-HT and
      noradrenaline reuptake inhibitor, sibutramine, in the rat.
AB  - 1. Sibutramine is a novel 5-hydroxytryptamine (5-HT) and noradrenaline reuptake
      inhibitor (serotonin-noradrenaline reuptake inhibitor, SNRI) which is currently
      being developed as a treatment for obesity. Sibutramine has been shown to
      decrease food intake in the rat. In this study we have used a variety of
      monoamine receptor antagonists to examine the pharmacological mechanisms
      underlying sibutramine-induced hypophagia. 2. Individually-housed male Sprague
      Dawley rats were maintained on reversed phase lighting with free access to food
      and water. Drugs were administered at 09 h 00 min and food intake was monitored
      over the following 8 h dark period. 3. Sibutramine (10 mg kg-1, p.o.) produced a
      significant decrease in food intake during the 8 h following drug administration.
      This hypophagic response was fully antagonized by the alpha 1-adrenoceptor
      antagonist, prazosin (0.3 and 1 mg kg-1, i.p.), and partially antagonized by the
      beta 1-adrenoceptor antagonist, metoprolol (3 and 10 mg kg-1, i.p.) and the 5-HT
      receptor antagonists, metergoline (non-selective; 0.3 mg kg-1, i.p.); ritanserin
      (5-HT2A/2C; 0.1 and 0.5 mg kg-1, i.p.) and SB200646 (5-HT2B/2C; 20 and 40 mg kg
      1, p.o.). 4. By contrast, the alpha 2-adrenoceptor antagonist, RX821002 (0.3 and
      1 mg kg-1, i.p.) and the beta 2-adrenoceptor antagonist, ICI 118,551 (3 and 10 mg
      kg-1, i.p.) did not reduce the decrease in food intake induced by sibutramine. 5.
      These results demonstrate that beta 1-adrenoceptors, 5-HT2A/2C-receptors and
      particularly alpha 1-adrenoceptors, are involved in the effects of sibutramine on
      food intake and are consistent with the hypothesis that sibutramine-induced
      hypophagia is related to its ability to inhibit the reuptake of both
      noradrenaline and 5-HT, with the subsequent activation of a variety of
      noradrenaline and 5-HT receptor systems.

PMID- 9283693
TI  - NANC transmitters in the female pig urethra--localization and modulation of
      release via alpha 2-adrenoceptors and potassium channels.
AB  - 1. To investigate further the release, localization and identity of a non
      nitrergic mediator of smooth muscle relaxation in the female pig urethra, we
      studied the effects of drugs acting at alpha 2-adrenoceptors or K+ channels, the
      effects of capsaicin and chemical sympathectomy, and the actions of several
      transmitter candidates. 2. Electrical field stimulation (EFS; frequencies above
      12 Hz) of spontaneously contracted smooth muscle strips from the female pig
      urethra evoked long-lasting, frequency-dependent relaxations in the presence of
      prazosin, scopolamine, and NG-nitro-L-arginine. Treatment with the selective
      alpha 2-adrenoceptor agonist UK-14 304 markedly reduced the relaxations evoked by
      EFS at all frequencies tested (16-30 Hz). The inhibitory effect of UK-14 304 was
      completely antagonized by the alpha 2-adrenoceptor antagonist rauwolscine. The
      muscarinic M1 receptor antagonist, pirenzepine, or exogenously administered
      carbachol, did not have any effects on the electrically evoked relaxations. 3.
      Inhibition of high conductance Ca2+ activated K+ channels by iberiotoxin or
      charybdotoxin significantly enhanced the relaxations evoked by EFS at all
      frequencies. However, inhibition of voltage-sensitive K+ channels with 4
      aminopyridine or dendrotoxin-1, treatment with the ATP-sensitive K+ channel
      blocker, glibenclamide, or treatment with the high and low conductance Ca2+
      activated K+ channel blockers, tetraethylammonium chloride and apamin, had no
      effect on the relaxations evoked by EFS. 4. Electrically evoked relaxations were
      not affected by adrenergic denervation with 6-hydroxydopamine (6-OHDA) at any
      frequency. However, treatment with 6-OHDA abolished prazosin-sensitive
      electrically induced contractions, and a long-lasting relaxation was revealed.
      Treatment with capsaicin, believed to damage selectively a subpopulation of
      primary afferent fibres, did not affect basal tone or relaxations evoked by EFS.
      5. Exogenously applied vasoactive intestinal polypeptide (VIP), pituitary
      adenylate cyclase-activating peptide (PACAP)-27, PACAP-38, adenosine, ATP and 5
      hydroxy-tryptamine caused relaxations of the urethral preparations, whereas
      prostaglandin E2 and calcitonin gene-related peptide had no effects. VIP 10-28,
      alpha, beta-methylene-ATP, reactive blue-2, suramin or indomethacin did not
      reduce the electrically-evoked relaxations at any frequency. However, the
      relaxations were slightly reduced by trypsin or alpha-chymotrypsin. 6. The
      present results suggest that the release of the unknown mediator in the female
      pig urethra can be modulated via alpha 2-adrenoceptors and high conductance Ca2+
      activated K+ channels. Furthermore, the mediator does not appear to be localized
      to or released from adrenergic or capsaicin-sensitive sensory nerve-endings. The
      identity of the transmitter remains to be established.

PMID- 9283695
TI  - Involvement of interleukin-1 beta, nerve growth factor and prostaglandin E2 in
      endotoxin-induced localized inflammatory hyperalgesia.
AB  - 1. Intraplantar endotoxin (ET) injection (1.25 micrograms) into the hind paw of
      rats resulted in a localized inflammatory hyperalgesia, as assessed by paw
      pressure (PP), paw immersion (PI), tail flick (TF) and hot plate (HP) tests. 2.
      ET injection resulted in a significant elevation in the levels of interleukin-1
      beta (IL-1 beta) and nerve growth factor (NGF) in the injected foot as compared
      with the non-injected foot. This increase was attenuated by intraperitoneal
      injections of dexamethasone (200 and 400 micrograms kg-1) and to a lesser extent
      by indomethacin (2 and 8 mg kg-1). 3. The tripeptide Lys-D-Pro-Val, which is
      known to antagonize IL-1 beta and prostaglandin E2 (PGE2) reversed mechanical
      hyperalgesia, as assessed by the PP test, and reduced significantly thermal
      hyperalgesia, as assessed by the HP and TF tests. 4. IL-1ra reversed both
      mechanical (PP) and thermal (PI) nociceptive thresholds tested on the injected
      leg and significantly reduced thermal hyperalgesia, as assessed by the HP and TF
      tests. 5. A sheep, anti-mouse NGF antiserum reversed mechanical hyperalgesia (PP
      test) but had little or no effect on thermal hyperalgesia (PI, HP and TF tests).
      6. Our results indicate the importance of IL-1 beta, NGF and prostaglandin E2
      (PGE2) in the development of ET induced hyperalgesia and the possible existence
      of different mechanisms underlying thermal and mechanical as well as central and
      peripheral hyperalgesia.

PMID- 9283696
TI  - Study of the in vivo and in vitro cardiovascular effects of a hydralazine-like
      vasodilator agent (HPS-10) in normotensive rats.
AB  - 1. In this work, the cardiovascular effects of HPS-10, a new vasodilator agent,
      were studied in rats. 2. In conscious normotensive rats, oral administration of
      HPS-10 (4-9 mg kg-1) produced a dose-related and long-lasting fall in systolic
      arterial blood pressure (ED30 of 5.32 mg kg-1), accompanied by an increase in
      heart rate (ED30 of 8.43 mg kg-1). This tachycardia was totally inhibited by
      pretreatment with (+/-)-propranolol (10 mg kg-1, p.o.). 3. In anaesthetized
      normotensive rats, HPS-10 (0.3-0.6 mg kg-1, i.v.) produced a gradual, dose
      dependent and sustained decrease in systolic, diastolic and mean arterial
      pressure (MAP) (ED30 for MAP of 0.41 mg kg-1, i.v.), accompanied by a significant
      bradycardia at high doses (> 0.4 mg kg-1; ED20 of 0.61 mg kg-1, i.v.). HPS-10
      (0.5 mg kg-1, i.v.) did not modify the positive chronotropic effects induced by
      intravenous administration of noradrenaline (NA; 5 micrograms kg-1), angiotensin
      II (AII; 0.2 microgram kg-1) and nicotine (200 micrograms kg-1) but markedly
      inhibited the hypertensive response produced by these agents. 4. In rat isolated
      rubbed aorta, HPS-10 (0.1-1 mM) non-competitively and with almost equal
      effectiveness antagonized the contractions induced by NA, AII (in normal Krebs
      solution) and Ca2+ (in depolarizing Ca(2+)-free high-K+ 50 mM solution). In the
      experiments in Ca(2+)-free medium, HPS-10 (1 mM) considerably inhibited the
      contractions induced by NA, AII and caffeine in rat aorta. 5. Furthermore, in the
      studies with radioactive Ca2+, HPS-10 (1 mM) did not modify the basal uptake of
      45Ca2+ but strongly decreased the influx of 45Ca2+ induced by NA, AII and K+ in
      rat aortic rings. 6. In rat isolated atria, HPS-10 (1 mM) produced a positive
      inotropic/negative chronotropic effect. 7. HPS-10 (0.3 mM) significantly
      inhibited the sustained and transient Ba2+ inward current (IBa) recorded in whole
      cell clamped rat aortic myocytes. 8. These results indicate that the non
      selective vasorelaxant effects of HPS-10 in rat aortic rings can be attributed to
      transmembrane Ca(2+)-antagonist activity and an intracellular action on smooth
      muscle cells. The direct vasodilator action of HPS-10 observed in rat isolated
      aorta may be responsible for the HPS-10 hypotensive activity in anaesthetized
      normotensive rats.

PMID- 9283698
TI  - Capsaicin and neurokinin A-induced bronchoconstriction in the anaesthetised
      guinea-pig: evidence for a direct action of menthol on isolated bronchial smooth
      muscle.
AB  - 1. For many years menthol has been used in the treatment of respiratory disorders
      although, a bronchodilator effect of menthol has yet to be described. Using the
      bronchoconstrictors capsaicin (acting via stimulating the release of
      neuropeptides from sensory afferents) and neurokinin A (NKA) we have raised
      airways resistance in the guinea-pig (GP) and studied the effect of menthol on
      both capsaicin and NKA-induced bronchoconstriction in vivo. In vitro the effect
      of menthol on acetylcholine (ACh) and KCl precontracted GP bronchi was also
      studied. 2. GP (n = 13) were anaesthetized (urethane 1.5 g kg-1, i.p.) and a
      bolus injection of capsaicin (7.5 micrograms ml-1, i.v.) or infusion of NKA (1
      microgram min-1, i.v.) was given either in the presence of air (0.81 min-1) or
      air impregnated with menthol vapour (7.5 micrograms l-1) freely breathed from a
      tracheal cannula via a T-piece. Airways resistance (Raw) and ventilation were
      measured throughout. Bronchi of mean internal diameter (1029 + 73.6 microns; n =
      24) were removed from GP (n = 16) and mounted in the Cambustion myograph.
      Bronchial rings were maximally precontracted with 80 mM KCl or 2 mM ACh.
      Relaxation due to a cumulative dose of menthol (1- 3000 microM) was measured. 3.
      Menthol produced a significant (P < 0.05) 51.3% reversal of the capsaicin-induced
      increase in Raw, and also inhibited the significant (P < 0.05) reduction in
      minute ventilation (Ve) associated with the capsaicin-induced increased in Raw.
      Menthol also caused a significant (P < 0.05) 41% reversal of the NKA-induced
      increase in Raw. The NKA-induced decrease in Ve was again significantly (P <
      0.05) reversed with menthol inhalation. Menthol caused a significant (P < 0.001)
      dose-dependent relaxation of KCl and ACh precontracted bronchi. 4. We have shown
      that menthol attenuates both capsaicin and NKA-induced bronchoconstriction in
      vivo and relaxes KCl and ACh preconstricted bronchi in vitro. Menthol inhibition
      of NKA and capsaicin-induced bronchoconstriction could be, in part, explained by
      a direct action of menthol on bronchial smooth muscle.

PMID- 9283697
TI  - Differential effect of L-NAME and S-methyl-isothiourea on leukocyte emigration in
      carrageenin-soaked sponge implants in rat.
AB  - 1. The role of nitric oxide (NO) in leukocyte (polymorphonuclear cells, monocytes
      and lymphocytes) emigration was studied in a model of carrageenin-sponge implants
      in rats. 2. The subcutaneous implantation of 1% (w/v) of lambda-carrageenin
      soaked sponges elicited an inflammatory response that was characterized by a time
      related increase in leukocyte infiltration in the sponges and increased levels of
      nitrite in the exudate. Total leukocyte infiltration and nitrite production were
      maximal at 24 h and decreased after 48 and 96 h. The mononuclear cell influx was
      maximal at 48 h (21% of the total leukocytes). Therefore, this time point was
      used in the successive experiments. 3. Polymorphonuclear cell (PMN) and
      lymphocyte infiltration in the sponges significantly increased when rats were
      treated with the non-specific NO-synthase (NOS) inhibitor, NG-nitro-L-arginine
      methylester (L-NAME) (1 mg ml-1) in drinking water ad libitum). Monocyte
      emigration was not affected by L-NAME treatment. The nitrite levels in the
      exudate of L-NAME-treated rats were significantly reduced. The concomitant
      ingestion of L-arginine (30 mg ml-1) resulted in a reversion of the L-NAME
      effect, while D-arginine (30 mg ml-1) had no effect, indicating the involvement
      of the L-arginine: NO pathway. 4. Administration of L-NAME resulted also in an
      increased release of tumour necrosis factor-alpha (TNF-alpha) and prostacyclin
      (measured as the stable metabolite, 6-keto-PGF 1 alpha). L-NAME had no effect on
      monocyte chemoattractant protein-1 (MCP-1) release in the exudate. 5. Since L
      NAME may have effects on the local blood flow, phenylephrine (0.034 mg ml-2) in
      drinking water) was used as it has an effect on the local blood flow similar to L
      NAME. Phenylephrine had no effect on either leukocyte emigration, or on nitrite,
      TNF-alpha, prostacyclin or MCP-1 accumulation in the exudate. 6. In contrast, the
      more selective iNOS inhibitor S-methyl-isothiourea (SMT) (10 micrograms ml-1) in
      drinking water) significantly reduced PMNs and lymphocyte influx in the sponge
      having no effect on monocyte influx. Moreover, SMT decreased nitrite production
      in the exudate to a comparable extent as L-NAME. 7. Administration of SMT
      significantly reduced MCP-1 release in the exudate, without an effect on TNF
      alpha or prostacyclin production. Moreover SMT did not produce any changes in
      local blood flow. 8. Our results show that a different outcome of the
      inflammatory process can be obtained depending on the types of NOS inhibitor
      used.

PMID- 9283699
TI  - Induction of neutrophil chemotactic factor production by staurosporine in rat
      peritoneal neutrophils.
AB  - 1. Incubation of rat peritoneal neutrophils in medium containing various
      concentrations of staurosporine (6.4-64 nM) increased the neutrophil chemotactic
      activity in the conditioned medium in a time- and concentration-dependent manner.
      2. Separation of the neutrophil chemotactic activity in the conditioned medium by
      isoelectric focusing revealed that staurosporine (64 nM) stimulated the
      production of basic (pH > 8) neutrophil chemotactic factors, while TPA (12-O
      tetradecanoylphorbol 13-acetate, 49 nM) stimulated the production of both basic
      (pH > 8) and acidic (pH 5) neutrophil chemotactic factors. 3. Determination by
      immunoassay of cytokine-induced neutrophil chemoattractant (CINC)-1, -2 alpha, -2
      beta and -3 in the conditioned medium at 4 h revealed that staurosporine (64 nM)
      and TPA (49 nM) strongly stimulated the production of CINC-3 (staurosporine,
      133.0 +/- 3.8; TPA, 26.7 +/- 1.0; control, 0.32 +/- 0.01 ng ml-1, means +/-
      s.e.mean from four samples) compared to CINC-1 (staurosporine, 55.0 +/- 1.2; TPA,
      12.2 +/- 0.3; control, 0.56 +/- 0.01 ng ml-1), and CINC-2 alpha (staurosporine,
      1.09 +/- 0.03; TPA, 0.90 +/- 0.02; control, < 0.10 ng ml-1). CINC-2 beta was
      below the detectable amount (< 0.078 ng ml-1). 4. The level of CINC-3 mRNA in the
      peritoneal neutrophils was determined by reverse transcription-polymerase chain
      reaction. Staurosporine (64 nM) and TPA (49 nM) enhanced the level of CINC-3 mRNA
      time-dependently, but had no effect on GAPDH mRNA levels. 5. Production of
      staurosporine-induced neutrophil chemotactic factor was inhibited by the protein
      kinase C inhibitors, H-7 (IC50, 12.3 microM), calphostin C (IC50, 0.77 microM)
      and Ro 31-8425 (24.3% inhibition at 10 microM), and by the tyrosine kinase
      inhibitor, genistein (IC50, 68.5 microM). Production of TPA-induced neutrophil
      chemotactic factor was also inhibited by both inhibitors. 6. Both the
      staurosporine- and the TPA-induced increase in CINC-3 mRNA levels were suppressed
      by H-7 and genistein.

PMID- 9283700
TI  - Role of endothelin receptors, calcium and nitric oxide in the potentiation by
      endothelin-1 of the sympathetic contraction of rabbit ear artery during cooling.
AB  - 1. To examine further the potentiation by endothelin-1 on the vascular response
      to sympathetic stimulation, we studied the isometric response of isolated
      segments, 2 mm long, from the rabbit central ear artery to electrical field
      stimulation (1-8 Hz), under different conditions, at 37 degrees C and during
      cooling (30 degrees C). 2. Electrical stimulation produced frequency-dependent
      contraction, which was reduced (about 63% for 8 Hz) during cooling. At 30 degrees
      C, but not at 37 degrees C, endothelin-1 (1, 3 and 10 nM) potentiated the
      contraction to electrical stimulation in a dose-dependent way (from 43 +/- 7% to
      190 +/- 25% for 8 Hz). 3. This potentiation by endothelin-1 was reduced by the
      antagonist for endothelin ETA receptors BQ-123 (10 microM) but not by the
      antagonist for endothelin ETB receptors BQ-788 (10 microM). The agonist for
      endothelin ETB receptors IRL-1620 (0.1 microM) did not modify the contraction to
      electrical stimulation. 4. The blocker of L-type Ca2+ channels verapamil (10
      microM l-1) reduced (about 72% for 8 Hz) and the unspecific blocker of Ca(2+)
      channels NiCl2 (1 mM) practically abolished (about 98%), the potentiating effects
      of endothelin-1 found at 30 degrees C. 5. Inhibition of nitric oxide synthesis
      with NG-nitro-L-arginine (L-NOARG, 0.1 mM) increased the contraction to
      electrical stimulation at 30 degrees C more than at 37 degrees C (for 8 Hz, this
      increment was 297 +/- 118% at 30 degrees C, and 66 +/- 15% at 37 degrees C).
      Endothelium removal increased the contraction to electrical stimulation at 30
      degrees C (about 91% for 8 Hz) but not at 37 degrees C. Both L-NOARG and
      endothelium removal abolished the potentiating effects of endothelin-1 on the
      response to electrical stimulation found at 30 degrees C. 6. These results in the
      rabbit ear artery suggest that during cooling, endothelin-1 potentiates the
      contraction to sympathetic stimulation, which could be mediated at least in part
      by increasing Ca2+ entry after activation of endothelin ETA receptors. This
      potentiating effect of endothelin-1 may require the presence of an inhibitory
      tone due to endothelial nitric oxide.

PMID- 9283701
TI  - The role of cyclic nucleotides in guinea-pig bladder contractility.
AB  - 1. The effects of phosphodiesterase (PDE) inhibition and forskolin pretreatment
      on the contractile responses of guinea-pig urinary bladder strips to electrical
      field stimulation, carbachol, ATP and KCl were studied. 2. Inhibition of cyclic
      AMP-specific PDE4 isozymes by rolipram significantly reduced the contractile
      response of bladder strips to field stimulation. Rolipram also suppressed the
      contractile response to low concentrations of carbachol, but potentiated the
      response to high concentrations. The contractile response to ATP was
      significantly reduced by rolipram treatment, but that to KCl was unaltered. 3.
      Inhibition of cyclic GMP-specific PDE5 isozymes by zaprinast had no effects on
      the contractile response of bladder strips to field stimulation, ATP or KCl.
      Zaprinast suppressed the contractile responses to 1 microM carbachol and
      potentiated the response to high concentrations. 4. Contractile responses to
      field stimulation and to carbachol after pretreatment with the adenylyl cyclase
      activator, forskolin, were qualitatively similar to those caused by rolipram
      treatment. beta-Adrenoceptor blockade with propranolol partially reversed the
      inhibitory effects of rolipram on the response to field stimulation. 5. Rolipram
      significantly reduced the contractile response of bladder strips from sensitized
      guinea-pigs to ovalbumin challenge, but zaprinast was ineffective. PDE inhibition
      had similar effects on the responsiveness of control and of sensitized guinea-pig
      bladder strips to field stimulation, carbachol, ATP and KCl. 6. The data suggest
      that the contractile response of guinea-pig bladder strips can be modified by
      increases in cyclic AMP levels.

PMID- 9283702
TI  - Characterization of [3H]-prostaglandin E2 binding to prostaglandin EP4 receptors
      expressed with Semliki Forest virus.
AB  - 1. The human prostaglandin EP4 receptor has been expressed by use of the Semliki
      Forest virus system. 2. In cell membranes [3H]-prostaglandin E2 ([3H]-PGE2) bound
      to a high affinity site with a Kd of 1.12 +/- 0.3 nM and a Bmax of 3.1 +/- 0.3
      pmol mg-1 protein. 3. In competition studies the rank order of potency for
      prostaglandins was PGE2 = PGE1 > > PGE2 alpha = PGI2. 4. The binding of [3H]-PGE2
      to cell membranes was inhibited by approximately 60% by the addition of
      guanylnucleotides, suggesting that this proportion of the receptors was G-protein
      coupled. 5. [3H]-PGE2 binding was increased by greater than 200% by the addition
      of divalent cations, with little change in the IC50 of PGE2. 6. In saturation
      studies removal of divalent cations and addition of GTP gamma S resulted in a 65%
      reduction in the Bmax with no change in the Kd. These results are consistent with
      the ligand labelling two states of the receptor R*, a high affinity state and
      R*G, a high affinity G protein coupled state.

PMID- 9283703
TI  - Profile of SB-204269, a mechanistically novel anticonvulsant drug, in rat models
      of focal and generalized epileptic seizures.
AB  - 1. Earlier optimization of structure-activity relationships in a novel series of
      4-(benzoylamino)-benzopyrans, led to the discovery of SB-204269 (trans-(+)-6
      acetyl-4S-(4-fluorobenzoylamino)-3,4-dihydro-2, 2-dimethyl-2H-benzo[b]pyran-3R
      ol, hemihydrate), a potent orally-active anticonvulsant in the mouse maximal
      electroshock seizure threshold (MEST) test. 2. Studies have now been undertaken
      to determine the effects of SB-204269 in a range of seizure models and tests of
      neurological deficits in rats. In addition, the compound has been evaluated in a
      series of in vitro mechanistic assays. 3. SB-204269 proved to be an orally
      effective anticonvulsant agent, at doses (0.1-30 mg Kg-1) devoid of overt
      behavioural depressant properties, in models of both electrically (MEST and
      maximal electroshock (MEST)) and chemically (i.v. pentylenetetrazol (PTZ)
      infusion)-evoked tonic extension seizures. However, the compound did not inhibit
      PTZ-induced myoclonic seizures at doses up to 30 mg kg-1, p.o. 4. SB-204269 also
      selectively reduced focal electrographic seizure activity in an in vitro elevated
      K+ rat hippocampal slice model at concentrations (0.1-10 microM) that had no
      effect on normal synaptic activity and neuronal excitability. 5. In all of these
      seizure models, SB-204269 was equivalent or better than the clinically
      established antiepileptic drugs carbamazepine and lamotrigine, in terms of
      anticonvulsant potency and efficacy. 6. Unlike SB-204269, the corresponding trans
      3S,4R enantiomer, SB-204268, did not produce marked anticonvulsant effects, an
      observation in accord with previous findings for other related pairs of trans
      enantiomers in the benzopyran series. 7. In the rat accelerating rotarod test, a
      sensitive paradigm for the detection of neurological deficits such as sedation
      and motor incoordination, SB-204269 was inactive even at doses as high as 200 mg
      kg-1, p.o. This was reflected in the excellent therapeutic index (minimum
      significantly effective dose in the rotarod test/ED50 in the MES test) for SB
      204269 of > 31, as compared to equivalent values of only 7 and 13 for
      carbamazepine and lamotrigine, respectively. 8. At concentrations (> or = 10
      microM) well above those required to produce anticonvulsant activity in vivo
      (i.e. 0.1 microM in brain), SB-204269 did not interact with many of the well
      known mechanistic targets for established antiepileptic drugs (e.g. Na+ channels
      or GABAergic neurotransmission). Subsequent studies have shown that the
      anticonvulsant properties of SB-204269 are likely to be mediated by a novel
      stereospecific binding site present in the CNS. 9. The overall efficacy profile
      in rodent seizure models, together with a minimal liability for inducing
      neurological impairment and an apparently unique mechanism of action, highlight
      the therapeutic potential of SB-204269 for the treatment of refractory partial
      and generalized tonic-clonic seizures.

PMID- 9283704
TI  - Characterization of the binding of [3H]-SB-204269, a radiolabelled form of the
      new anticonvulsant SB-204269, to a novel binding site in rat brain membranes.
AB  - 1. SB-204269 (trans-(+)-6-acetyl-4S-(4-fluorobenzoylamino)-3, 4-dihydro-2,2
      dimethyl-2H-benzol[b]pyran-3R-ol, hemihydrate) shows potent anticonvulsant
      activity in a range of animal seizure models, with a lack of neurological or
      cardiovascular side-effects. The profile of the compound suggests that it may
      have a novel mechanism of action. This study describes the characteristics of a
      binding site for [3H]-SB-204269 in rat forebrain membranes. 2. Specific [3H]-SB
      204269 binding was saturable and analysis indicated binding to a homogenoeous
      population of non-interacting binding sites with a dissociation constant (KD) of
      32 +/- 1 nM and a maximum binding capacity (Bmax) of 253 +/- 18 fmol mg-1
      protein. Kinetic studies indicated monophasic association and dissociation.
      Binding was similar in HEPES or Tris-HCl buffers and was unaffected by Na+, K+,
      Ca2+ or Mg2+ ions. Specific binding was widely distributed in brain, but was
      minimal in a range of peripheral tissues. 3. Specific [3H]-SB-204269 binding was
      highly stereoselective, with a 1000 fold difference between the affinities of SB
      204269 and its enantiomer SB-204268 for the binding site. The affinities of
      analogues of SB-204269 for binding can be related to their activities in the
      mouse maximal electroshock seizure threshold (MEST) test of anticonvulsant
      action. 4. None of the standard anticonvulsant drugs, phenobarbitone, phenytoin,
      sodium valproate, carbamazepine, diazepam and ethosuximide, or the newer
      anticonvulsants, lamotrigine, vigabatrin, gabapentin and levetiracetam, showed
      any affinity for the [3H]-SB-204269 binding site. A wide range of drugs active at
      amino acid receptors, Na+ or K+ channels or various other receptors did not
      demonstrate any affinity for the binding site. 5. These studies indicate that SB
      204269 possesses a specific CNS binding site which may mediate its anticonvulsant
      activity. This binding site does not appear to be directly related to the sites
      of action of other known anticonvulsant agents, but may have an important role in
      regulating neuronal excitability.

PMID- 9283705
TI  - Characterization of the signalling pathways involved in ATP and basic fibroblast
      growth factor-induced astrogliosis.
AB  - 1. A brief challenge of rat astrocytes with either alpha, beta-methyleneATP
      (alpha, beta-meATP) or basic fibroblast growth factor (bFGF) resulted, three days
      later, in morphological differentiation of cells, as shown by marked elongation
      of astrocytic processes. The P2 receptor antagonist suramin prevented alpha, beta
      meATP- but not bFGF-induced astrocytic elongation. Similar effects on astrocytic
      elongation were also observed with ATP and other P2 receptor agonists (beta,
      gamma meATP, ADP beta S, 2meSATP and, to a lesser extent, UTP). 2. Pertussis
      toxin completely abolished alpha, beta-meATP- but not bFGF-induced effects. No
      effects were exerted by alpha, beta-meATP on cyclic AMP production; similarly,
      neomycin had no effects on elogation of processes induced by the purine analogue,
      suggesting that adenylyl cyclase and phospholipase C are probably not involved in
      alpha, beta-meATP-induced effects (see also the accompanying paper by Centemeri
      et al., 1997). The tyrosine-kinase inhibitor genistein greatly reduced bFGF- but
      not alpha, beta-meATP-induced astrocytic elongation. 3. Challenge of cultures
      with alpha, beta-meATP rapidly and concentration-dependently increased [3H]
      arachidonic acid (AA) release from cells, suggesting that activation of
      phospholipase A2 (PLA2) may be involved in the long-term functional effects
      evoked by purine analogues. Consistently, exogenously added AA markedly elongated
      astrocytic processes. Moreover, various PLA2 inhibitors (e.g. mepacrine and
      dexamethasone) prevented both the early alpha, beta-meATP-induced [3H]-AA release
      and/or the associated long-term morphological changes, without affecting the
      astrocytic elongation induced by bFGF. Finally, the protein kinase C (PKC)
      inhibitor H7 fully abolished alpha, beta-meATP- but not bFGF-induced effects. 4.
      Both alpha, beta-meATP and bFGF rapidly and transiently induced the nuclear
      accumulation of Fos and Jun. Both c-fos and c-jun induction by the purine
      analogue could be fully prevented by pretreatment with suramin. In contrast, the
      effects of bFGF were unaffected by this P2 receptor antagonist. 5. It was
      concluded that alpha, beta-meATP- and bFGF-morphological differentiation of
      astrocytes occurs via independent transductional pathways. For the purine
      analogue, signalling involves a Gi/G(o) protein-coupled P2Y-receptor which may be
      linked to activation of PLA2 (involvement of an arachidonate-sensitive PKC is
      speculated); for bFGF, a tyrosine kinase receptor is involved. Both pathways
      merge on some common intracellular target, as suggested by induction of primary
      response genes, which in turn may regulate late response genes mediating long
      term phenotypic changes of astroglial cells. 6. These findings implicate P2
      receptors as novel targets for the pharmacological regulation of reactive
      astrogliosis, which has intriguing implications in nervous system diseases
      characterized by degenerative events.

PMID- 9283706
TI  - Characterization of the Ca2+ responses evoked by ATP and other nucleotides in
      mammalian brain astrocytes.
AB  - 1. This study was aimed at characterizing ATP-induced rises in cytosolic free
      calcium ion, [Ca2+]i, in a population of rat striatal astrocytes loaded with the
      fluorescent Ca2+ probe Fura2, by means of fluorescence spectrometry. 2. ATP
      triggered a fast and transient elevation of [Ca2+]i in a concentration-dependent
      manner. The responses of the purine analogues 2-methylthio-ATP (2-meSATP),
      adenosine-5'-O-(2-thiodiphosphate) (ADP beta S), as well as uridine-5'
      triphosphate (UTP) resembled that of ATP, while alpha, beta-methylene-ATP (alpha,
      beta-meATP) and beta, gamma-methylene-ATP (beta, gamma-meATP) were totally
      ineffective. 3. Suramin (50 microM) had only a minor effect on the ATP response,
      whereas pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (5 microM)
      significantly depressed the maximum response. 4. Extracellular Ca2+ did not
      contribute to the observed [Ca2+]i rise: removing calcium from the extracellular
      medium (with 1 mM EGTA) or blocking its influx by means of either Ni2+ (1 mM) or
      Mn2+ (1 mM) did not modify the nucleotide responses. 5. Furthermore, after
      preincubation with 10 microM thapsigargin, the nucleotide-evoked [Ca2+]i
      increments were completely abolished. In contrast, 10 mM caffeine did not affect
      the responses, suggesting that thapsigargin-, but not caffeine/ryanodine
      sensitive stores are involved. 6. Both application of the G-protein blocker
      guanosine-5'-O-(2-thiodiphosphate) (GDP beta S) (1 mM) and preincubation with
      pertussis toxin (PTx) (350 ng ml-1) partially inhibited the nucleotide-mediated
      responses. Moreover, the phospholipase C (PLC) inhibitor U-73122, but not its
      inactive stereoisomer U-73343 (5 microM), significantly reduced the ATP-evoked
      [Ca2+]i rise. 7. In conclusion, our results suggest that, in rat striatal
      astrocytes, ATP-elicited elevation of [Ca2+]i is due solely to release from
      intracellular stores and is mediated by a G-protein-linked P2Y receptor,
      partially sensitive to PTx and coupled to PLC.

PMID- 9283707
TI  - Influence of AMPA/kainate receptors on extracellular 5-hydroxytryptamine in rat
      midbrain raphe and forebrain.
AB  - 1. The regulation of 5-hydroxytryptamine (5-HT) release by excitatory amino acid
      (EAA) receptors was examined by use of microdialysis in the CNS of freely
      behaving rats. Extracellular 5-HT was measured in the dorsal raphe nucleus (DRN),
      median raphe nucleus (MRN), nucleus accumbens, hypothalamus, frontal cortex,
      dorsal and ventral hippocampus. 2. Local infusion of kainate produced increases
      in extracellular 5-HT in the DRN and MRN. Kainate infusion into forebrain sites
      had a less potent effect. 3. In further studies of the DRN and nucleus accumbens,
      kainate-induced increases in extracellular 5-HT were blocked by the EAA receptor
      antagonists, kynurenate and 6,7-dinitroquinoxaline-2,3-dione (DNQX). 4. The
      effect of infusing kainate into the DRN or nucleus accumbens was attenuated or
      abolished by tetrodotoxin (TTX), suggesting that the increase in extracellular 5
      HT is dependent on 5-HT neuronal activity. In contrast, ibotenate-induced lesion
      of intrinsic neurones did not attenuate the effect of infusing kainate into the
      nucleus accumbens. Thus, the effect of kainate in the nucleus accumbens does not
      depend on intrinsic neurones. 5. Infusion of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolaproprionate (AMPA) into the DRN and nucleus accumbens induced
      nonsignificant changes in extracellular 5-HT. Cyclothiazide and diazoxide, which
      attenuate receptor desensitization, greatly enhanced the effect of AMPA on 5-HT
      in the DRN, but not in the nucleus accumbens. 6. In conclusion, AMPA/kainate
      receptors regulate 5-HT in the raphe and in forebrain sites.

PMID- 9283708
TI  - Evidence that methyl arachidonyl fluorophosphonate is an irreversible cannabinoid
      receptor antagonist.
AB  - 1. Methyl arachidonyl fluorophosphonate (MAFP) (1 microM) significantly
      attenuated the ability of WIN 55,212-2, CP 55,940, (-)-delta 9
      tetrahydrocannabinol (THC), nabilone and (R)-(+)-arachidonoyl-1'-hydroxy-2'
      propylamide (methanandamide) to inhibit electrically-evoked isometric
      contractions of the myenteric plexus-longitudinal muscle preparation of guinea
      pig small intestine. 2. The sizes of the maximal responses to WIN 55,212-2 and CP
      55,940 decreased significantly in the presence of 1 microM MAFP. 3. MAFP (1
      microM) essentially abolished the inhibitory effects on the twitch response of
      the highest concentration of methanandamide used (3.162 microM). The dextral
      shift it induced in the log concentration-response curve of nabilone was non
      parallel. In contrast, the dextral shift in the log concentration-response curve
      of THC produced by MAFP did not deviate significantly from parallelism and was
      relatively small with a mean value of 3.45 and 95% confidence limits of 1.19 and
      13.08. 4. MAFP (1 microM) did not attenuate the effects of normorphine or
      clonidine on the twitch response of the myenteric plexus-longitudinal muscle
      preparation or affect the contractile response of this preparation to
      acetylcholine. 5. When administered by itself at concentrations of 1 to 1000 nM,
      MAFP had no detectable effect on the twitch response of the myenteric plexus
      longitudinal muscle preparation. 6. These results support the hypothesis that
      MAFP is an irreversible cannabinoid CB1 receptor antagonist that possesses some
      degree of selectivity.

PMID- 9283709
TI  - Characterization of alpha 2-adrenoceptors mediating contraction of dog saphenous
      vein: identity with the human alpha 2A subtype.
AB  - 1. In the dog saphenous vein alpha 1- and alpha 2-adrenoceptors mediate
      noradrenaline-induced contractions in vitro. In order to study the alpha 2
      adrenoceptor in isolation, alpha 1-adrenoceptors were inactivated by treatment of
      tissues with the alkylating agent phenoxybenzamine (3.0 microM for 30 min) in the
      presence of rauwolscine (1 microM) to protect alpha 2-adrenoceptors. 2.
      Noradrenaline-induced contractions of tissues treated with phenoxybenzamine were
      antagonized competitively by the selective alpha 2-adrenoceptor antagonist
      rauwolscine, pKB = 8.63 +/- 0.07 (means +/- s.e. mean; n = 3), consistent with an
      interaction at alpha 2-adrenoceptors. 3. Noradrenaline was a full agonist at
      alpha 2-adrenoceptors in dog saphenous vein. By use of the method of partial
      receptor alkylation and analysis of concentration-effect curve data by direct,
      operational model fitting methods, the affinity (pKA) and efficacy (tau) were
      5.74 +/- 0.07 and 7.50 +/- 1.05, respectively (n = 6). Nine other agonists which
      were examined each had affinities higher than noradrenaline, but with the
      exception of the imidazoline, A-54741 (5,6-dihydroxy-1,2,3,4-tetrahydro-1
      naphthyl-imidazoline) had relatively lower efficacies. 4. To compare the alpha 2
      adrenoceptor in dog saphenous vein to the human recombinant subtypes, the
      affinities of twenty-one compounds were estimated in functional studies in the
      dog saphenous vein and in radioligand binding studies for the human alpha 2A,
      alpha 2B and alpha 2C receptor subtypes expressed in Chinese hamster lung (CHL)
      cells. 5. Of twenty-one compounds examined in ligand binding studies, only nine
      had greater than ten fold selectivity for one human receptor subtype over either
      of the other two. These compounds were A-54741, oxymetazoline, guanfacine,
      guanabenz, prazosin, spiroxatrine, tolazoline, WB 4101 and idazoxan. In dog
      saphenous vein, their affinities (pKA and pKB for agonists and antagonists
      respectively) were: A-54741 (pKA = 8.03 +/- 0.05), oxymetazoline (pKA = 7.67 +/-
      0.09), guanfacine (pKA = 6.79 +/- 0.03); guanabenz (pKA = 7.02 +/- 0.13);
      prazosin (pKB = 5.19 +/- 0.08), spiroxatrine (pKB = 6.59 +/- 0.04), tolazoline
      (pKB = 6.21 +/- 0.07), WB 4101 (pKB = 7.42 +/- 0.09) and idazoxan (pKB = 7.11 +/-
      0.08). 6. Comparisons of affinity estimates for these nine compounds at the
      receptor in dog saphenous vein and at the human recombinant subtypes suggest that
      the vascular receptor is most similar to the h alpha 2A subtype; correlation
      coefficients (r) were 0.82 (h alpha 2A), 0.24 (h alpha 2B) and 0.04 (h alpha 2C).

PMID- 9283710
TI  - Long lasting smooth muscle relaxation by a novel PACAP analogue in guinea-pig and
      primate airways in vitro.
AB  - 1. We compared the relaxant effect of pituitary adenylate cyclase activating
      peptide (PACAP) 1-27 with that of a newly developed PACAP 1-27 analogue,
      [Arg15,20,21Leu17]-PACAP-Gly-Lys-Arg-NH2, in the guinea-pig trachea and primate
      bronchi in vitro (n = 4-5). 2. In the guinea-pig trachea precontracted by a
      submaximally effective carbachol concentration (0.1 microM), cumulative
      administration of PACAP 1-27 and the beta 2-adrenoceptor agonist salbutamol (3 nM
      3 microM) caused significant and concentration-dependent smooth muscle
      relaxation, with salbutamol being approximately one log-step more potent in this
      model. However, in primate bronchi precontracted by carbachol (0.1 microM),
      cumulative administration of PACAP 1-27 and salbutamol caused concentration
      dependent smooth muscle relaxation with very similar potencies and maximum
      relaxant effects. 3. In the guinea-pig trachea, non-cumulative administration of
      the PACAP 1-27 analogue and the original PACAP 1-27 (0.3-3 microM) caused
      concentration-dependent relaxation with a very similar maximum relaxant effect
      and potency. However, the onset and offset of action was markedly slower for the
      PACAP 1-27 analogue than for the original PACAP 1-27 (< 90% versus < 10% of peak
      relaxation remaining 6 h after administration). Separate experiments confirmed
      that the PACAP 1-27 analogue also caused significant relaxation with slower onset
      and offset of action than did the original PACAP 1-27 in primate bronchi. 4.
      Peptidase inhibition by captopril (10 microM) and phosphoramidon (1 microM)
      significantly increased the maximum relaxant effect and duration of action of
      PACAP 1-27 but not of the PACAP 1-27 analogue, during the 3 h of observation in
      the guinea-pig trachea. 5. We conclude that [Arg15,20,21Leu17]-PACAP-Gly-Lys-Arg
      NH2 produces significant, concentration-dependent and sustained airway smooth
      muscle relaxation in vitro. The sustained relaxant effect is due, at least in
      part, to the PACAP 1-27 analogue being less susceptible to cleavage by peptidases
      than the original peptide PACAP 1-27.

PMID- 9283711
TI  - Carrier-dependent and Ca(2+)-dependent 5-HT and dopamine release induced by (+)
      amphetamine, 3,4-methylendioxymethamphetamine, p-chloroamphetamine and (+)
      fenfluramine.
AB  - 1. The mechanism underlying 5-hydroxytryptamine (5-HT) and/or dopamine release
      induced by (+)-amphetamine ((+)-Amph), 3,4-methylendioxymethamphetamine (MDMA), p
      chloroamphetamine (pCA) and (+)-fenfluramine ((+)-Fen) was investigated in rat
      brain superfused synaptosomes preloaded with the 3H neurotransmitters. 2. Their
      rank order of potency for [3H]-5-HT-releasing activity was the same as for
      inhibition of 5-HT uptake (pCA > or = MDMA > or = (+)-Fen > > (+)-Amph).
      Similarly, their rank order as [3H]-dopamine releasers and dopamine uptake
      inhibitors was the same ((+)-Amph > > pCA = MDMA > > (+)-Fen). We also confirmed
      that the release induced by these compounds was prevented by selective
      transporter inhibitors (indalpine or nomifensine). 3. [3H]-5HT and/or [3H]
      dopamine release induced by all these compounds was partially (31-80%), but
      significantly Ca(2+)-dependent. Lack of extracellular Ca2+ did not alter uptake
      mechanisms nor did it modify the carrier-dependent dopamine-induced [3H]-dopamine
      release. (+)-Amph-induced [3H]-dopamine release and pCA- and MDMA-induced [3H]-5
      HT release were significantly inhibited by omega-agatoxin-IVA, a specific blocker
      of P-type voltage-operated Ca(2+)-channels, similar to the previous results on
      (+)-Fen-induced [3H]-5-HT release. 4. Methiothepin inhibited the Ca(2+)-dependent
      component of (+)-Amph-induced [3H]-dopamine release with high potency (70 nM), as
      previously found with (+)-Fen-induced [3H]-5-HT release. The inhibitory effect of
      methiothepin was not due to its effects as a transporter inhibitor or Ca(2+)
      channel blocker and is unlikely to be due to its antagonist properties on 5
      HT1/2, dopamine or any other extracellular receptor. 5. These results indicate
      that the release induced by these compounds is both 'carrier-mediated' and Ca(2+)
      dependent (possibly exocytotic-like), with the specific carrier allowing the
      amphetamines to enter the synaptosome. The Ca(2+)-dependent release is mediated
      by Ca(2+)-influx (mainly through P-type Ca(2+)-channels), possibly triggered by
      the drug interacting with an unknown intracellular target, affected by
      methiothepin, common to both 5-HT and dopamine synaptosomes.

PMID- 9283712
TI  - ATP release and contraction mediated by different P2-receptor subtypes in guinea
      pig ileal smooth muscle.
AB  - 1. The present study was addressed to clarify the subtypes of P2-purinoceptor
      involved in ATP release and contraction evoked by alpha, beta-methylene ATP
      (alpha, beta-mATP) and other P2-agonists in guinea-pig ileum. 2. alpha, beta-mATP
      100 microM produced a transient and steep contraction followed by ATP release
      from tissue segments. These maximum responses appeared with different time
      courses and their ED50 values were 5 and 25 microM, respectively. The maximum
      release of ATP by alpha, beta-mATP was markedly reduced by 250 microM suramin, 30
      microM pyridoxal-phosphate-6-azophenyl-2',5'-disulphonic acid (PPADS) and 30
      microM reactive blue 2 (RB-2), P2-receptor antagonists. However, the contractile
      response was inhibited by suramin, tetrodotoxin and atropine, but not by PPADS
      and RB-2. 3. Although the contraction caused by alpha, beta-mATP was strongly
      diminished by Ca(2+)-removal and nifedipine, and also by tetrodotoxin and
      atropine at 0.3 microM, the release of ATP was virtually unaffected by these
      procedures. 4. UTP, beta, gamma-methylene ATP (beta, gamma-mATP) and ADP at 100
      microM elicited a moderate release of ATP. The release caused by UTP was
      virtually unaffected by RB-2. However, these P2-agonists failed to elicit a
      contraction of the segment. 5. The potency order of all the agonists tested for
      the release of ATP was alpha, beta-mATP > UTP > beta, gamma-mATP > ADP. 6. In
      superfusion experiments with cultured smooth muscle cells from the ileum, alpha,
      beta-mATP (100 microM) enhanced the release of ATP 5 fold above the basal value.
      This evoked release was inhibited by RB-2. 7. These findings suggest that ATP
      release and contraction induced by P2-agonists such as alpha, beta-mATP in the
      guinea-pig ileum result mainly from stimulation of different P2-purinoceptors.
      P2Y-like purinoceptors on the smooth muscles and, probably, P2X-purinoceptors on
      cholinergic nerve terminals, respectively. However, the ATP release may also be
      mediated, in part, by P2U-receptors, because UTP caused RB-2-insensitive ATP
      release.

PMID- 9283713
TI  - Involvement of protein kinase C in the UTP-mediated potentiation of cyclic AMP
      accumulation in mouse J774 macrophages.
AB  - 1. We have investigated the effects of nucleotide analogues on cyclic AMP
      formation in mouse J774 macrophages and the mechanisms involved. 2. UTP, in the
      concentration range 0.1-100 microM, induced concentration-dependent potentiation
      of prostaglandin E1 (PGE1)-induced cyclic AMP formation, but had no effect on
      basal cyclic AMP formation. UDP showed an equal potency, while 2-methylthio ATP,
      alpha, beta-methylene ATP and beta,gamma-methylene ATP gave either a slight
      increase or had no effect at concentrations up to 100 microM. ATP, although 100
      fold less effective than UTP, also caused cyclic AMP potentiation, but had no
      effect on agonist-stimulated or basal cyclic AMP levels. 3. The cyclic AMP
      potentiation effect of UTP correlated with increased [Ca2+]i and inositol
      phosphate (IP) formation over the same concentration range. 4. Ionomycin, which
      evokes an increase in [Ca2+]i without affecting IP formation, did not cause an
      increase in cyclic AMP content, indicating that UTP-induced cyclic AMP regulation
      is not due to activation of Ca(2+)-sensitive adenylyl cyclase isoforms. 5.
      Although reduced, UTP potentiation was seen in cells incubated in a Ca(2+)-free
      and/or BAPTA-containing medium. Under these conditions, the UTP-increased IP
      accumulation was similarly reduced. 6. Exposure of cells to phorbol 12-myristate
      13-acetate (PMA) also increased PGE1 stimulation of cyclic AMP levels, and the
      UTP-induced potentiation of cyclic AMP formation was inhibited by either
      staurosporine or Ro 31-8220. Pretreatment of cells with PMA for 4-24 h resulted
      in marked attenuation of UTP-stimulated cyclic AMP potentiation. 7. Pretreatment
      with pertussis toxin (24 h, 100 ng ml-1) did not significantly affect UTP-induced
      cyclic AMP potentiation and IP formation, although it increased the cyclic AMP
      response to PGE1. 8. Analysis of J774 cells by Western blotting with antibodies
      specific for different protein kinase C (PKC) isoforms shows the presence of the
      beta I, beta II, delta, epsilon, eta, mu, lambda and zeta isoforms. Moreover, UTP
      significantly increased the level of PKC beta I, beta II, delta, epsilon, mu,
      lambda and zeta immunoreactivity in the membrane fraction and decreased the
      cytosolic reactivity of PKC beta II, delta, epsilon and zeta. 9. Immunoblot
      studies also indicate the presence of type II adenylyl cyclase. 10. These results
      indicate that PKC is required for the potentiation of adenylyl cyclase activity
      by macrophage pyrimidinoceptors, which exhibit a higher specificity for UTP and
      UDP than for ATP.

PMID- 9283714
TI  - Comparison of the effects of sibutramine and other monoamine reuptake inhibitors
      on food intake in the rat.
AB  - 1. The effects of the potent 5-hydroxytryptamine (5-HT) and noradrenaline
      reuptake inhibitor (serotonin-noradrenaline reuptake inhibitor, SNRI),
      sibutramine, on the cumulative food intake of freely-feeding male Sprague-Dawley
      rats during an 8 h dark period were investigated and compared to those of the
      selective 5-HT reuptake inhibitor (selective serotonin reuptake inhibitor, SSRI),
      fluoxetine; the selective noradrenaline reuptake inhibitor, nisoxetine; the 5-HT
      and noradrenaline reuptake inhibitors, venlafaxine and duloxetine; and the 5-HT
      releaser and 5-HT reuptake inhibitor, (+)-fenfluramine. 2. Sibutramine (3 and 10
      mg kg-1, p.o.) and (+)-fenfluramine (1 and 3 mg kg-1, p.o.) produced a
      significant, dose-dependent decrease in food intake over the 8 h dark period.
      These responses became apparent within the first 2 h following drug
      administration. 3. Fluoxetine (3, 10 and 30 mg kg-1, p.o.), and nisoxetine (3, 10
      and 30 mg kg-1, p.o.) had no significant effect on food intake during the 8 h
      dark period. However, a combination of fluoxetine and nisoxetine (30 mg kg-1,
      p.o., of each) significantly decreased food intake 2 and 8 h after drug
      administration. 4. Venlafaxine (100 and 300 mg kg-1, p.o.) and duloxetine (30 mg
      kg-1, p.o.) also significantly decreased food intake in the 2 and 8 h following
      drug administration. 5. The results of this study demonstrate that inhibition of
      5-HT and noradrenaline reuptake by sibutramine, venlafaxine, duloxetine, or by a
      combination of fluoxetine and nisoxetine, markedly reduces food intake in freely
      feeding rats and suggest that this may be a novel approach for the treatment of
      obesity.

PMID- 9283716
TI  - Reduction of urinary 8-epi-prostaglandin F2 alpha during cyclo-oxygenase
      inhibition in rats but not in man.
AB  - 1. 8-epi-prostaglandin (PG) F2 alpha, a major F2 isoprostane, is produced in vivo
      by free radical-dependent peroxidation of lipid-esterified arachidonic acid. Both
      cyclo-oxygenase isoforms (COX-1 and COX-2) may also form free 8-epi-PGF2 alpha as
      a minor product. It has been recently seen in human volunteers that the overall
      basal formation of 8-epi-PGF2 alpha in vivo is mostly COX-independent and urinary
      8-epi-PGF2 alpha is therefore an accurate marker of 'basal' oxidative stress in
      vivo. 2. To test the validity of this marker in the rat, we evaluated in vivo the
      effect of COX inhibition on the formation of 8-epi-PGF2 alpha vs prostanoids. Two
      structurally unrelated COX inhibitors (naproxen: 30 mg kg-1 day-1; indomethacin:
      4 mg kg-1 day-1) were given i.p. to rats kept in metabolic cages. In vivo
      formation of 8-epi-PGF2 alpha was assessed by measuring its urinary excretion.
      Prostanoid biosynthesis was assessed by measuring urinary excretion of major
      metabolites of thromboxane (TX) and prostacyclin (2,3-dinor-TXB1 and 2,3-dinor-6
      keto-PGF1 alpha). All compounds were selectively measured by
      immunopurification/gas chromatography-mass spectrometry. 3. Naproxen reduced
      urinary excretion of 2,3-dinor-TXB1 and 2,3-dinor-6-keto-PGF1 alpha but,
      unexpectedly, also that of 8-epi-PGF2 alpha (82, 49 and 52% inhibition,
      respectively). Indomethacin had a similar effect (77, 69 and 55% inhibition).
      Esterified 8-epi-PGF2 alpha in liver and plasma remained unchanged after
      indomethacin. 4. These findings prompted us to re-assess the contribution of COX
      activity to the systemic production of 8-epi-PGF2 alpha in man. We gave naproxen
      (1 g day-1) to healthy subjects (four nonsmokers and four smokers). Urinary 8-epi
      PGF2 alpha remained unchanged in the two groups (9.63 +/- 0.99 before vs 10.24 +/
      1.01 after and 20.14 +/- 3.00 vs 19.03 +/- 2.45 ng h-1 1.73 m-2), whereas there
      was a marked reduction of major urinary metabolites of thromboxane and
      prostacyclin (about 90% for both 11-dehydro-TXB2 and 2,3-dinor-TXB2; > 50% for
      2,3-dinor-6-keto-PGF1 alpha). 5. To investigate whether rat COX-1 produces 8-epi
      PGF2 alpha more efficiently than human COX-1, we measured the ex vivo formation
      of 8-epi-PGF2 alpha and TXB2 simultaneously in whole clotting blood. Serum levels
      of 8-epi-PGF2 alpha and TXB2 were similar in rats and man. 6. We conclude that a
      significant amount of COX-dependent 8-epi-PGF2 alpha is present in rat but not in
      human urine under normal conditions. This implies that urinary 8-epi-PGF2 alpha
      cannot be used as an index of near-basal oxidant stress in rats. On the other
      hand, our data further confirm the validity of this marker in man.

PMID- 9283715
TI  - Regulation of bradykinin B2-receptor expression by oestrogen.
AB  - 1. Tissue kallikrein is overexpressed in the kidney of female rats, this sexual
      dimorphism being associated with a greater effect of early blockade of bradykinin
      B2-receptors on female blood pressure phenotype. We evaluated the effect of
      ovariectomy and oestradiol benzoate (50 micrograms kg-1 every two days for two
      weeks) on the vasodepressor response to intra-arterial injection of bradykinin
      (150-900 ng kg-1) and on the expression of bradykinin B2-receptors. 2.
      Ovariectomy reduced the magnitude of the vasodepressor response to bradykinin and
      unmasked a secondary vasopressor effect. Oestrogen replacement restored the
      vasodepressor response to bradykinin in ovariectomized rats. 3. The vasodepressor
      responses to sodium nitroprusside (3-18 micrograms kg-1), acetylcholine (30-600
      ng kg-1), desArg9-bradykinin (150-900 ng kg-1) or prostaglandin E2 (30-600 ng kg
      1) were significantly reduced by ovariectomy. Oestrogen restored to normal the
      responses to desArg9-bradykinin, acetylcholine and prostaglandin E2, but not that
      to sodium nitroprusside. 4. B2-receptor mRNA levels were decreased by ovariectomy
      in the aorta and kidney and they were restored to normal levels by oestrogen.
      Neither ovariectomy nor oestradiol affected receptor expression in the heart and
      uterus. 5. These results indicate that oestrogen regulates B2-receptor gene
      expression and function. Since kinins exert a cardiovascular protective action,
      reduction in their vasodilator activity after menopause might contribute to the
      increased risk of pathological cardiovascular events. Conversely, the
      cardioprotective effects of oestrogen replacement might be, at least in part,
      mediated by activation of the kallikrein-kinin system.

PMID- 9283717
TI  - Investigation into the contractile response of melatonin in the guinea-pig
      isolated proximal colon: the role of 5-HT4 and melatonin receptors.
AB  - 1. The interaction of melatonin (N-acetyl-5-methoxytryptamine) with 5
      hydroxytryptamine4 (5-HT4) receptors and/or with melatonin receptors (ML1, ML2
      sites) has been assessed in isolated strips of the guinea-pig proximal colon. In
      the same preparation, the pharmacological profile of a series of melatonin
      agonists (2-iodomelatonin, 6-chloromelatonin, N-acetyl-5-hydroxytryptamine (N
      acetyl-5-HT), 5-methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT)) was
      investigated. 2. In the presence of 5-HT1/2/3 receptor blockade with methysergide
      (1 microM) and ondansetron (10 microM), melatonin (0.1 nM-10 microM), 5-HT (1 nM
      1 microM) and the 5-HT4 receptor agonist, 5-methoxytryptamine (5-MeOT: 1 nM-1
      microM) caused concentration-dependent contractile responses. 5-HT and 5-MeOT
      acted as full agonists with a potency (-log EC50) of 7.8 and 8.0, respectively.
      The potency value for melatonin was 8.7, but its maximum effect was only 58% of
      that elicited by 5-HT. 3. Melatonin responses were resistant to atropine (0.1
      microM), tetrodotoxin (0.3 microM), and to blockade of 5-HT4 receptors by SDZ
      205,557 (0.3 microM) and GR 125487 (3, 30 and 300 nM). The latter antagonist (3
      nM) inhibited 5-HT-induced contractions with an apparent pA2 value of 9.6 GR
      125487 antagonism was associated with 30% reduction of the 5-HT response maximum.
      Contractions elicited by 5-HT were not modified when melatonin (1 and 10 nM) was
      used as an antagonist. 4. Like melatonin, the four melatonin analogues
      concentration-dependently contracted colonic strips. The rank order of agonist
      potency was: 2-iodomelatonin (10.8) > 6-chloromelatonin (9.9) > or = N-acetyl-5
      HT (9.8) > or = 5-MCA-NAT (9.6) > melatonin (8.7), an order typical for ML2
      sites. In comparison with the other agonists, 5-MCA-NAT had the highest intrinsic
      activity. 5. The melatonin ML1B receptor antagonist luzindole (0.3, 1 and 3
      microM) had no effect on the concentration-response curve to melatonin. Prazosin,
      an alpha-adrenoceptor antagonist possessing moderate/ high affinity for melatonin
      ML2 sites did not affect melatonin-induced contractions at 0.1 microM. Higher
      prazosin concentrations (0.3 and 1 microM) caused a non-concentration-dependent
      depression of the maximal response to melatonin without changing its potency.
      Prazosin (0.1 and 1 microM) showed a similar depressant behaviour towards the
      contractile responses to 5-MCA-NAT. 6. In the guinea-pig proximal colon,
      melatonin despite some structural similarity with the 5-HT4 receptor agonist 5
      MeOT, does not interact with 5-HT4 receptors (or with 5-HT1/2/3 receptors). As
      indicated by the rank order of agonist potencies and by the inefficacy of
      luzindole, the most likely sites of action of melatonin are postjunctional ML2
      receptors. However, this assumption could not be corroborated with the use of
      prazosin as this 'ML2 receptor antagonist' showed only a non-concentration
      dependent depression of the maximal contractile response to both melatonin and 5
      MCA-NAT. Further investigation with the use of truly selective antagonists at
      melatonin ML2 receptors is required to clarify this issue.

PMID- 9283719
TI  - Differential effects of lovastatin on mitogen induced calcium influx in human
      cultured vascular smooth muscle cells.
AB  - 1. In this study the effect of lovastatin, an inhibitor of cholesterol and
      isoprenoid synthesis, on the rises in intracellular calcium concentration
      ([Ca2+]i) induced by platelet derived growth factor BB (PDGF-BB), angiotensin II
      (AII), low density lipoproteins (LDL) and foetal calf serum (FCS) was examined in
      human cultured vascular smooth muscle cells (VSMC) from saphenous vein. Changes
      in [Ca2+]i were measured in cell suspensions by the Ca2+ sensitive probe, fura 2.
      2. Incubation with lovastatin for 24-26 h markedly reduced the peak rise and
      sustained phase of [Ca2+]i elevation in response to PDGF-BB but the responses to
      AII, LDL and FCS were unaffected. Further experiments showed that lovastatin
      pretreatment inhibited PDGF-BB induced Ca2+ influx but not intracellular Ca2+
      release. This inhibition could be overcome by co-incubation with mevalonic acid.
      3. Pretreatment of cells with the heterotrimeric G protein inhibitor pertussis
      toxin for up to 24 h completely abolished AII-induced [Ca2+]i rises but the
      response to PDGF-BB was unaffected. 4. The tyrosine kinase inhibitor genistein
      largely abolished PDGF-BB-induced [Ca2+]i elevation but had no significant effect
      on AII-induced responses. 5. Pre-incubation with lovastatin had no effect on the
      level of tyrosine phosphorylation of PDGF-beta receptors (as measured by Western
      blot) in response to the PDGF-BB ligand. 6. PDGF-BB elicits Ca2+ influx via a
      tyrosine kinase-dependent mechanism distinct from the heterotrimeric G protein
      coupled pathway utilized by AII. Lovastatin most likely acts by inhibition of
      isoprenylation (via blockade of isoprenoid synthesis) of an intermediate molecule
      involved in PDGF-BB-induced Ca2+ influx.

PMID- 9283718
TI  - The involvement of tumour necrosis factor-alpha in the protective effects of 17
      beta oestradiol in splanchnic ischaemia-reperfusion injury.
AB  - 1. Tumour necrosis factor-alpha (TNF-alpha) is a cytokine that is implicated in
      the pathogenesis of ischaemic states and atherosclerosis. We tested the
      hypothesis that the vasoprotective effects of the oestrogens may be mediated in
      vivo by inhibition of the formation of TNF-alpha. 2. Anaesthetized rats,
      subjected to total occlusion of the superior mesenteric artery and the coeliac
      trunk for 45 min developed a severe shock state resulting in a fatal outcome
      within 75-90 min after the release of occlusion. Sham-operated animals were used
      as controls. 3. Splanchnic artery occlusion (SAO) shocked rats had a marked
      hypotension, enhanced levels of TNF-alpha in serum and macrophages, leukopenia
      and increased ileal leukocyte accumulation, studied by means of myeloperoxidase
      activity (MPO). Furthermore, aortae from SAO rats showed a marked hyporeactivity
      to phenylephrine (PE, 1 nM-10 microM), reduced responsiveness to acetylcholine
      (ACh, 10 nM-10 microM) and an increased staining for intercellular adhesion
      molecule-1 (ICAM-1). 4. In vivo administration of 17 beta oestradiol (500
      micrograms kg-1, i.m., three hours before the induction of SAO) increased
      survival rate (100%, 4 h after SAO), enhanced mean arterial blood pressure;
      reduced serum TNF-alpha (25 +/- 5 u ml-1 vs 379 +/- 16 u ml-1), ameliorated
      leukopaenia and reduced ileal MPO (0.7 +/- 0.02 u 10(-3) g-1 tissue vs 4.2 +/-
      0.4 u 10(-3) g-1 tissue). Furthermore aortae from SAO rats treated with 17 beta
      oestradiol exhibited a greater contractile response to phenylephrine, improved
      responsiveness to ACh and a blunted staining of ICAM-1. Finally 17 beta
      oestradiol, added in vitro to peritoneal macrophages collected from untreated SAO
      rats, significantly reduced TNF-alpha production. 5. Our results suggest that
      inhibition of TNF-alpha in vivo may explain, at least in part, the vasoprotective
      effects of oestrogens.

PMID- 9283720
TI  - Inhibitory effect of a new steroidal saponin, OSW-1, on ovarian functions in
      rats.
AB  - 1. This study was undertaken to determine the effects of OSW-1 (3 beta, 16 beta,
      17 alpha-trihydroxycholest-5-en-22-one 16-O-(2-O-4-methoxybenzoyl-beta-D
      xylopyranosyl)- (1-->3)-(2-O-acetyl-alpha-L-arabinopyranoside)) on the pituitary
      ovarian system and the functions of aortic smooth muscle. 2. A single s.c.
      injection of OSW-1 (9 micrograms kg-1) on the morning of pro-oestrus inhibited
      the occurrence of the expected next pro-oestrus, whereas administration of OSW-1
      at a dose of 4.5 micrograms kg-1 did not affect the oestrous cycle. OSW-1
      treatment on the day of dioestrus-1 did not affect the oestrous cycle. 3. At
      doses of 4.5 and 9 micrograms kg-1 OSW-1, the serum oestradiol (E2) levels at the
      expected next pro-oestrus were significantly lower than in control (pro-oestrus).
      The serum luteinizing hormone (LH) levels 4 days after 9 micrograms kg-1 OSW-1
      treatment were also markedly lower than those of control. OSW-1 (4.5 micrograms
      kg-1) did not affect the levels of inhibin, progesterone and gonadotrophins on
      the same day. 4. OSW-1 did not inhibit the preovulatory LH surge which occurs on
      the afternoon of pro-oestrus day. 5. The expression of mRNA coding for the
      cholesterol side chain cleavage cytochrome P-450 (p450scc), an ovarian steroidal
      limiting enzyme, was suppressed at 24 and 96 h after OSW-1 treatment. 6.
      Administration of OSW-1 (9 micrograms kg-1) tended to reduce the relaxation of
      isolated thoracic aorta ring preparations induced by acetylcholine, while there
      was no difference in the relaxation induced by sodium nitroprusside. 7. Our
      results show that OSW-1 inhibits ovarian E2 secretion and that the decrease in E2
      secretion may contribute to its effects on the oestrous cycle and the sensitivity
      of the thoracic aorta to relaxation. The decrease in the levels of ovarian
      steroids induced by OSW-1 may be due to its direct inhibitory action on the gene
      expression of the steroidal enzyme and on the proliferation of granulosa cells in
      the ovary.

PMID- 9283721
TI  - Catecholamine modulatory effects of nepicastat (RS-25560-197), a novel, potent
      and selective inhibitor of dopamine-beta-hydroxylase.
AB  - 1. Inhibitory modulation of sympathetic nerve function may have a favourable
      impact on the progression of congestive heart failure. Nepicastat is a novel
      inhibitor of dopamine-beta-hydroxylase, the enzyme which catalyses the conversion
      of dopamine to noradrenaline in sympathetic nerves. The in vitro pharmacology and
      in vivo catecholamine modulatory effects of nepicastat were investigated in the
      present study. 2. Nepicastat produced concentration-dependent inhibition of
      bovine (IC50 = 8.5 +/- 0.8 nM) and human (IC50 = 9.0 +/- 0.8 nM) dopamine-beta
      hydroxylase. The corresponding R-enantiomer (RS-25560-198) was approximately 2-3
      fold less potent than nepicastat. Nepicastat had negligible affinity (> 10
      microM) for twelve other enzymes and thirteen neurotransmitter receptors. 3.
      Administration of nepicastat to spontaneously hypertensive rats (SHRs) (three
      consecutive doses of either 3, 10, 30 or 100 mg kg-1, p.o.; 12 h apart) or beagle
      dogs (0.05, 0.5, 1.5 or 5 mg kg-1, p.o.; b.i.d., for 5 days) produced dose
      dependent decreases in noradrenaline content, increases in dopamine content and
      increases in dopamine/noradrenaline ratio in the artery (mesenteric or renal),
      left ventricle and cerebral cortex. At the highest dose studied, the decreases in
      tissue noadrenaline were 47%, 35% and 42% (in SHRs) and 88%, 91% and 96% (in
      dogs) in the artery, left ventricle and cerebral cortex, respectively. When
      tested at 30 mg kg-1, p.o., in SHRs, nepicastat produced significantly greater
      changes in noradrenaline and dopamine content, as compared to the R-enantiomer
      (RS-25560-198), in the mesenteric artery and left ventricle. 4. Administration of
      nepicastat (2 mg kg-1, b.i.d, p.o.) to beagle dogs for 15 days produced
      significant decreases in plasma concentrations of noradrenaline and increases in
      plasma concentrations of dopamine and dopamine/noradrenaline ratio. The peak
      reduction (52%) in plasma concentration of noradrenaline and the peak increase
      (646%) in plasma concentration of dopamine were observed on day-6 and day-7 of
      dosing, respectively. 5. The findings of this study suggest that nepicastat is a
      potent, selective and orally active inhibitor of dopamine-beta-hydroxylase which
      produces gradual modulation of the sympathetic nervous system by inhibiting the
      biosynthesis of noradrenaline. This drug may, therefore, be of value in the
      treatment of cardiovascular disorders associated with over-activation of the
      sympathetic nervous system, such as congestive heart failure.

PMID- 9283722
TI  - The effects of neuroleptic and tricyclic compounds on BKCa channel activity in
      rat isolated cortical neurones.
AB  - 1. The actions of several neuroleptic and tricyclic compounds were examined on
      the large conductance Ca(2+)-activated K+ (BKCa) channel present in neurones
      isolated from the rat motor cortex. 2. Classical neuroleptic compounds including
      chlorpromazine and haloperidol applied to the intracellular surface of inside-out
      patches produced a concentration-dependent reduction in BKCa channel activity.
      Similar effects were observed when these compounds were applied to the
      extracellular surface of outside-out patches. 3. In contrast, the atypical
      neuroleptic compounds clozapine and sulpiride did not affect BKCa channel
      activity (100 nM-1 mM) in either inside-out or outside-out patches, while 10
      microM pimozide produced 73% of the inhibition produced by 10 microM
      chlorpromazine. 4. BKCa channel activity was also unaffected by application of
      structurally related tricyclic compounds including the anti-cholinesterase
      tacrine and the anti-epileptic carbamazepine. The tricyclic antidepressant drug
      amitriptyline was found to inhibit BKCa channel activity but was much less
      effective than the classical neuroleptic compounds. 5. It is concluded that
      compounds belonging to the classical neuroleptic group of drugs inhibit BKCa
      channel activity in the rat motor cortex in a structurally-specific manner. This
      observation may be of clinical significance as it may contribute to some of the
      side effects associated with classical neuroleptic drug therapy.

PMID- 9283723
TI  - Agonist and antagonist modulation of [35S]-GTP gamma S binding in transfected CHO
      cells expressing the neurotensin receptor.
AB  - 1. The functional interaction of the cloned rat neurotensin receptor with
      intracellular G-proteins was investigated by studying the binding of the
      radiolabelled guanylyl nucleotide analogue [35S]-GTP gamma S induced by
      neurotensin to membranes prepared from transfected Chinese hamster ovary (CHO)
      cells. 2. The agonist-induced binding of [35S]-GTP gamma S was only detected in
      the presence of NaCl in the incubation buffer. However, it was also demonstrated
      that the binding of [3H]-neurotensin to its receptor was inhibited by NaCl. In
      the presence of 50 mM NaCl, the binding of the labelled nucleotide was about 2
      fold increased by stimulation with saturating concentrations of neurotensin (EC50
      value of 2.3 +/- 0.9 nM). 3. The stimulation of [35S]-GTP gamma S binding by
      neurotensin was mimicked by the stable analogue of neurotensin, JMV-449 (EC50
      value of 1.7 +/- 0.4 nM) and the neurotensin related peptide neuromedin N (EC50
      value of 21 +/- 6 nM). 4. The NT-induced [35S]-GTP gamma S binding was
      competitively inhibited by SR48692 (pA2 value of 9.55 +/- 0.28), a non-peptide
      neurotensin receptor antagonist. SR48692 alone had no effect on the specific
      binding of [35S]-GTP gamma S. 5. The response to neurotensin was found to be
      inhibited by the aminosteroid U-73122, a putative inhibitor of phospholipase C
      dependent processes, indicating that this drug may act at the G-protein level. 6.
      Taken together, these results constitute the first characterization of the
      exchange of guanylyl nucleotides at the G-protein level that is induced by the
      neuropeptide neurotensin after binding to its receptor.

PMID- 9283724
TI  - Intrarenal haemodynamics and renal dysfunction in endotoxaemia: effects of nitric
      oxide synthase inhibition.
AB  - 1. This study investigated the effects of low dose endotoxin (lipopolysaccharide,
      LPS) on (i) systemic haemodynamics, (ii) renal blood flow (RBF), (iii) renal
      cortical and medullary perfusion and (iv) renal function in the anaesthetized
      rat. We have also investigated the effects of nitric oxide (NO) synthase (NOS)
      inhibition with NG-methyl-L-arginine (L-NMMA) on the alterations in systemic and
      renal haemodynamics and renal function caused by endotoxin. 2. Infusion of low
      dose LPS (1 mg kg-1 over 30 min, n = 6) caused a late fall in mean arterial blood
      pressure (MAP, at 5 and 6 h after LPS), but did not cause an early (at 1-4 h
      after LPS) hypotension. The pressor effect of noradrenaline (NA, 1 microgram kg
      1, i.v.) was significantly reduced at 1 to 6 h after LPS (vascular
      hyporeactivity). Infusion of L-NMMA (50 micrograms kg-1 min-1 commencing 60 min
      before LPS and continued throughout the experiment, n = 7) abolished the delayed
      hypotension and significantly attenuated the vascular hyporeactivity to NA (at 2
      6 h). 3. Infusion of LPS (1 mg kg-1 over 30 min, n = 6) caused a rapid (within 2
      h) decline in renal function (measured by inulin clearance) in the absence of a
      significant fall in MAP or renal blood flow (RBF). L-NMMA (n = 7) attenuated the
      impairment in renal function caused by LPS so that the inulin clearance in LPS
      rats treated with L-NMMA was significantly greater than in LPS-rats treated with
      vehicle (control) at 3-6 h after infusion of LPS. 4. Endotoxaemia also caused a
      significant reduction in renal cortical, but not medullary perfusion (measured as
      Laser Doppler flux). Infusion of L-NMMA caused a significant further fall in
      cortical perfusion and a significant fall in medullary perfusion in the absence
      of changes in RBF. 5. Infusion of LPS resulted in a progressive increase in the
      plasma levels of nitrite/nitrate (an indicator of the formation of NO), so that
      the plasma concentration of nitrite/nitrate was significantly higher than
      baseline at 150 to 330 min after LPS. Infusion of L-NMMA attenuated the rise in
      the plasma concentration of nitrite/nitrate (at 270 and 330 min, P < 0.05) caused
      by LPS. 6. Thus, the renal dysfunction caused by injection of low dose of
      endotoxin in the rat occurs in the absence of significant falls in blood pressure
      or total renal blood flow. Inhibition of NOS activity with L-NMMA attenuates the
      renal dysfunction caused by endotoxin (without improving intrarenal
      haemodynamics), suggesting that an overproduction of NO may contribute to the
      development of renal injury and dysfunction by causing direct cytotoxic effects.

PMID- 9283725
TI  - Location of the coronary arterial orifices in the normal heart.
AB  - We examined the coronary arterial orifices in relation to the aortic valve to
      determine the range of normality in 23 normal hearts from autopsied adults. We
      determined the position of the zones of apposition between leaflets, the size of
      the leaflets, the number, position, and shape of the coronary arterial orifices,
      and their relation to the sinutubular junction. The aortic valve had three
      leaflets in all specimens, nearly equally spaced around the aorta. The left
      coronary artery arose within the left posterior aortic sinus (of Valsalva) in 16
      (69%) specimens, above the sinutubular junction in five (22%), and at the level
      of the junction in two (9%). The distance of the left orifice from the zone of
      apposition between the left posterior and anterior aortic leaflets was between
      13% and 61% of the width of the aortic sinus at the sinutubular junction. The
      right coronary artery arose within the anterior aortic sinus in 18 (78%)
      specimens, above the junction in three (13%), and at the level of the junction in
      two (9%). The distance of the orifice from the zone of apposition between the
      leaflets hinged from the anterior and right posterior aortic sinuses was between
      5% and 62% of the width of the aortic sinus at the sinutubular junction. An
      accessory coronary orifice was found in the anterior aortic sinus in 17 (74%)
      specimens, whereas a third orifice in this sinus was found in five hearts. The
      coronary arterial orifices are usually located within the aortic sinuses below
      the sinutubular junction, but are rarely centrally located. Accessory coronary
      arterial orifices are found in the majority of the anterior aortic sinuses.

PMID- 9283726
TI  - Anatomic variant of the posterior interventricular coronary artery: implications
      for coronary angioplasty in acute myocardial infarction.
AB  - Acute thrombotic occlusion of an infarct-related artery is frequently found in
      patients presenting with myocardial infarction. In a patient with acute inferior
      wall myocardial infarction complicated by continuous chest pain and hemodynamic
      instability, emergency diagnostic coronary arteriography demonstrated a patent,
      infarct-related, "pseudo" right coronary artery while, in fact, this vessel was a
      rare anatomic variant of the posterior interventricular branch with very early
      origin from the right coronary artery and the true right coronary artery was
      completely occluded by a thrombotic obstruction. Accurate anatomic-angiographic
      interpretation of the angiogram was crucial for successful performance of
      emergency recanalization and revascularization of the true right coronary artery
      with laser and balloon angioplasty. Once antegrade flow was restored another rare
      coronary variant was discovered, i.e., a sinoatrial node artery arising from the
      middle portion of the newly patent right coronary artery.

PMID- 9283727
TI  - Is there such a thing as the "tendon of the infundibulum" in the heart?
AB  - The fibrous skeleton of the heart has featured prominently in anatomical and
      surgical descriptions, although all its purported components are difficult to
      demonstrate. In descriptions of the skeleton, there have been repeated references
      to the presence of a tendon (or ligament) between the aortic and pulmonary roots.
      Such a tendon is rarely, if ever, discussed in the context of surgical procedures
      being carried out on the ventricular outflow tracts. Our study was undertaken,
      therefore, to investigate the existence and nature of such a tendon or ligament.
      Serial transverse sections were made through roots of aorta and pulmonary trunk
      in an intact fetal heart. In addition, ten normal adult hearts were dissected to
      display the components of the fibrous skeleton of the heart. No discrete fibrous
      or elastic structure could be detected in the tissue plane between the aortic
      sinuses and the subpulmonary muscular infundibulum, although a fascial strand was
      observed in one heart. Apart from this specimen, the space between the free
      standing muscular subpulmonary infundibulum and the sinuses of aorta hearing the
      coronary arteries was occupied only by loose fibroareolar tissue. The initial
      presence of the ligament was described following studies of animal and macerated
      human hearts. Subsequently, it would seem its existence has been passed down
      through generations of morphologists and surgeons without its presence being
      reconfirmed. We have been unable to demonstrate any structure approximating to
      the initial illustrations.

PMID- 9283728
TI  - Anatomy of the peritoneal aspect of the deep inguinal ring: implications for
      laparoscopic inguinal herniorrhaphy.
AB  - There are a number of important structures to be avoided in suturing or stapling
      during laparoscopic inguinal herniorrhaphy, not all of which are easily
      identifiable at laparoscopy. This is particularly so of the ductus deferens.
      Measurements were taken of the angle made by the ductus deferens with testicular
      vessels, and of the thickness of tissue in the vicinity of the internal ring into
      which sutures or staples are likely to be inserted. The angle (mean +/- SD) made
      by the ductus with testicular vessels was 38.6 degrees +/- 4.4 degrees on the
      right, and 48.6 degrees +/- 7.2 degrees on the left (P < 0.05) (measurements for
      right and left sides taken from different cadavers). Thickness of tissue around
      the ring (peritoneum, transversalis fascia and intervening connective tissue)
      varies at different sites, being greatest lateral to the testicular vessels (2.2
      +/- 0.4 mm) and least over the ductus (0.2 +/- 0.1 mm). The angle measured
      constitutes the apex of the "triangle of doom" (Spaw et al., 1991. J.
      Laparoendoscopic Surg. 1:269-277) and with its use the position of the ductus
      deferens may be predicted and the underlying external iliac vessels avoided when
      stapling during herniorrhaphy.

PMID- 9283729
TI  - Prediction of the femoral neck-shaft angle from the length of the femoral neck.
AB  - A total of 171 adult South Indian femora, devoid of gross pathology, are used to
      measure the neck-shaft angle, length of the neck, intertrochanteric apical axis
      length, maximum vertical diameter of the head, kinematic radius, and maximum
      femoral length. The neck-shaft angle ranges from 120 degrees to 136 degrees with
      a mean of 126.7 degrees and no significant side difference. The angle
      significantly and positively correlates with neck length, intertrochanteric
      apical axis length, kinematic radius, and minimum femoral length (P < 0.001) but
      not with the vertical diameter of the head. Regression equations for the neck
      shaft angle against the correlated parameters are derived but only that against
      the length of the neck is strongly significant. From those correlations, 1) the
      neck-shaft angle can be estimated from a proximal femoral fragment, and 2) the
      required size of the length of the neck can be determined to design prostheses
      for the restoration of normal neck-shaft angle. Further, any estimated defective
      angle can be of help for forensic identification of an individual with
      pathological changes leading to an abnormal gait.

PMID- 9283730
TI  - Surgical landmarks of the ureter in the cadaveric female pelvis.
AB  - Our purpose was to delineate the course of the ureter in the female pelvis in
      relationship to several important surgical landmarks. Ten female cadavers with
      undissected pelves were used. The ureter was identified at the pelvic brim and
      traced inferiorly to the bladder. Sets of measurements (+/- 0.1 cm) that help
      define the location of the ureter were obtained at the three landmarks; the
      ischial spine, the obturator canal and the insertion of the arcus tendineus on
      the pubic bone. The mean distances from the ureter to the pelvic floor were
      ischial spine, 3.2 +/- 0.1 cm; obturator canal, 3.2 +/- 0.1 cm; and the insertion
      of the arcus tendineus on the pubic bone, 1.6 +/- 0.1 cm. The mean distances from
      the arcus tendineus to the pelvic floor were ischial spine, 1.9 +/- 0.1 cm;
      obturator canal, 2.8 +/- 0.1 cm; and the insertion of the arcus tendineus on the
      pubic bone, 3.2 +/- 0.1 cm. This study defines the relationship of the ureter to
      the pelvic floor through measurements taken at three landmarks. The data should
      be useful to pelvic surgeons and are important for the development of future
      surgical techniques.

PMID- 9283731
TI  - Variability of the obturator vessels.
AB  - The obturator artery and vein are usually described as branches or tributaries of
      the internal iliac vessels although variations with connections to the external
      iliac or inferior epigastric vessels have been reported. Because these anomalous
      vessels are at risk in groin or pelvic surgeries that require dissection or
      suturing along the pelvic rim, we measured the frequency of these variations in
      105 pelvic walls (45 in the United States and 60 in China). Our data show that 70
      82% of pelvic halves and 83-90% of whole pelves had an artery, vein, or both in
      the variant position. Arteries were most often found in the normal position only
      but normal and anomalous veins were most frequently found together. These data
      show that it is far more common to find a vessel coursing over the pelvic rim at
      this site than not and have implications for both pelvic surgeons and anatomists.

PMID- 9283732
TI  - Introduction to histology through the use of familiar objects: innovative
      teaching module.
AB  - To introduce first-year medical students to fundamental concepts in histology and
      facilitate interpretation of two-dimensional images in the context of the three
      dimensional nature of the object, a simple teaching module consisting of active
      exercises plus group discussions, using familiar objects from everyday use, was
      planned. In the process of mentally reconstructing sections through familiar
      objects, and representing in diagrams the appearance of these sections, students
      learned the use of common histology terms; the value of studying sections in
      series and at different planes; and spatial relationships of a) a nucleus within
      a cell, and b) tissue components within solid and hollow organs. Their
      understanding of these concepts was found to be good when evaluated by a multiple
      choice-questions test, suggesting that this is an effective method for
      introducing beginners to fundamentals of histology.

PMID- 9283733
TI  - Philatelic introduction to the history of anatomy.
AB  - Representative postage stamps reproduced here provide an idea of the scope
      available for introducing the history of human anatomy. Included are ancient
      Greek pioneers, the reformer of human anatomy (Vesalius), the discoverer of the
      circulation of the blood (Harvey), the compound microscope, and well-known names
      in histology, neurohistology, and topographical anatomy.

PMID- 9283734
TI  - Subisthmic accessory thyroid gland in man: a case report and a review of thyroid
      anomalies.
AB  - Morphological variations of the thyroid gland are common and generally occur
      superior to the gland, reflecting its developmental origin. In this report we
      describe an accessory lobe located inferior to both lateral lobes and the
      isthmus. The accessory lobe was supplied by a branch of the right inferior
      thyroid artery and its vein drained via the plexus thyroideus impar. A discussion
      of thyroid anomalies is presented and a system for classifying variations of
      thyroid anatomy is proposed.

PMID- 9283735
TI  - Problem in diagnostic imaging: have you got the nerve?
AB  - This article poses a diagnostic problem commonly encountered in neuroradiology
      and otolaryngology. The solution and ensuing discussion focus on the anatomy of
      the posterior cranial fossa (with emphasis on the cerebellopontine angle) and the
      relevant pathology. Current methods of imaging the posterior cranial fossa are
      explained and their relative merits discussed.

PMID- 9283736
TI  - Problem in diagnostic imaging: behind the left renal vein.
AB  - This study presents, as diagnostic problems, computed tomographic scans from a
      selection of patients with suspected or known tumors, primary or secondary, in
      the retroperitoneal area, at the level of the renal hila. The study emphasizes
      the value of serial CT scans, and of three-dimensional reconstructions made from
      them, in distinguishing between tumor and incidental venous anomalies in this
      region, principally those involving communications between the left renal vein
      and the ascending lumbar vein.

PMID- 9283737
TI  - Play it again Sam.

PMID- 9283738
TI  - Show me the science--a cautionary tale.

PMID- 9283739
TI  - "Gestational age"?

PMID- 9283740
TI  - Hypertensive heart disease syndrome in women in a cardiology practice.
AB  - The authors hypothesized that a population of female patients exist whose
      historical and clinical findings are typical regarding hypertensive heart disease
      syndrome, so they can be readily identified in a clinical practice and benefit
      from specific therapy.

PMID- 9283741
TI  - Alternatives to conventional hormone replacement therapy.
AB  - Alternative medicines have become "mainstream" in their popularity and economic
      size. The most highly promoted and popular types of alterative medicines used for
      menopause are discussed, including mineral and vitamin supplements,
      phytoestrogens, natural hormones, and botanical/plant medicines.

PMID- 9283742
TI  - Chronic lower extremity ischemia.
AB  - With a careful history and physical examination, aided by the judicious use of
      noninvasive tests, the diagnosis of chronic lower extremity ischemia can be
      readily made. The definition and pathophysiology, diagnosis, and treatment of
      chronic lower extremity ischemia are discussed.

PMID- 9283743
TI  - Antiemetic therapy.
AB  - With the increasing prevalence of chemotherapy in the treatment of neoplasia,
      antiemetic therapies have become essential and sophisticated: phenothiazines,
      benzodiazepines, steroids, substituted benzamides, butryphenones,
      anticholinergics and antihistamines, cannabinoids, and the 5-HT 3 receptor
      antagonist are reviewed.

PMID- 9283744
TI  - The primary care physician's role in evaluating the pediatric amputee.
AB  - The clinician must have an understanding of the spectrum of potential problems
      that can occur in the pediatric patient with a limb deficiency. These various
      complications-osseous, nonosseous, infection, phantom limb phenomenon and pain,
      pre-existing conditions, and psychosocial-are discussed.

PMID- 9283745
TI  - Negotiating managed care contracts.
AB  - Physicians currently have a major opportunity to help guide the rapid evolution
      of managed care in the United States. General principles on how physicians can
      successfully negotiate a managed care contract are discussed.

PMID- 9283746
TI  - Troglitazone.

PMID- 9283747
TI  - Identifying distantly related protein sequences.

PMID- 9283749
TI  - Sisyphus and prediction of protein structure.
AB  - The problem of predicting protein structure from the sequence remains
      fundamentally unsolved despite more than three decades of intensive research
      effort. However, new and promising methods in three-dimensional (3D), 2D and 1D
      prediction have reopened the field. Mean-force-potentials derived from the
      protein databases can distinguish between correct and incorrect models (3D).
      Inter-residue contacts (2D) can be detected by analysis of correlated mutations,
      albeit with low accuracy. Secondary structure, solvent accessibility and
      transmembrane helices (1D) can be predicted with significantly improved accuracy
      using multiple sequence alignments. Some of these new prediction methods have
      proven accurate and reliable enough to be useful in genome analysis, and in
      experimental structure determination. Moreover, the new generation of theoretical
      methods is increasingly influencing experiments in molecular biology.

PMID- 9283748
TI  - Linguistic approaches to biological sequences.
AB  - Biologists have long made use of linguistic metaphors in describing and naming
      cellular processes involving nucleic acid and protein sequences. Indeed, it is
      very natural to view the genetic 'text' and its sequential transliterations in
      these terms. However, a metaphor is not a tool, and it is necessary to ask
      whether the techniques used in analyzing other kinds of languages, such as human
      and computer languages, can in fact be of any use in tackling problems in
      molecular biology. This paper reviews the work of the author and others in
      applying the methods of computational linguistics to biological sequences.

PMID- 9283750
TI  - Rapid protein fragment search using hash functions based on the Fourier
      transform.
AB  - MOTIVATION: Since the protein structure database has been growing very rapidly in
      recent years, the development of efficient methods for searching for similar
      structures is very important. RESULTS: This paper presents a novel method for
      searching for similar fragments of proteins. In this method, a hash vector (a
      vector of real numbers) is associated with each fixed-length fragment of three
      dimensional protein structure. Each vector consists of low-frequency components
      of the Fourier-like spectrum for the distances between C alpha atoms and the
      centroid. Then, we can analyze the similarity between fragments by evaluating the
      difference between hash vectors. The novel aspect of the method is that the
      following property is proved theoretically: if the root mean square distance
      between two fragments is small, then the distance between the hash vectors is
      small. Several variants of this method were compared with a naive method and a
      previous method using PDB data. The results show that the fastest one among the
      variants is 18-80 times faster than the naive method, and 3-10 times faster than
      the previous method.

PMID- 9283751
TI  - A method for identifying splice sites and translational start sites in eukaryotic
      mRNA.
AB  - This paper describes a new method for determining the consensus sequences that
      signal the start of translation and the boundaries between exons and introns
      (donor and acceptor sites) in eukaryotic mRNA. The method takes into account the
      dependencies between adjacent bases, in contrast to the usual technique of
      considering each position independently. When coupled with a dynamic program to
      compute the most likely sequence, new consensus sequences emerge. The consensus
      sequence information is summarized in conditional probability matrices which,
      when used to locate signals in uncharacterized genomic DNA, have greater
      sensitivity and specificity than conventional matrices. Species-specific versions
      of these matrices are especially effective at distinguishing true and false
      sites.

PMID- 9283752
TI  - The reversible Hill equation: how to incorporate cooperative enzymes into
      metabolic models.
AB  - MOTIVATION: Realistic simulation of the kinetic properties of metabolic pathways
      requires rate equations to be expressed in reversible form, because substrate and
      product elasticities are drastically different in reversible and irreversible
      reactions. This presents no special problem for reactions that follow reversible
      Michaelis-Menten kinetics, but for enzymes showing cooperative kinetics the full
      reversible rate equations are extremely complicated, and anyway in virtually all
      cases the full equations are unknown because sufficiently complete kinetic
      studies have not been carried out. There is a need, therefore, for approximate
      reversible equations that allow convenient simulation without violating
      thermodynamic constraints. RESULTS: We show how the irreversible Hill equation
      can be generalized to a reversible form, including effects of modifiers. The
      proposed equation leads to behaviour virtually indistinguishable from that
      predicted by a kinetic form of the Adair equation, despite the fact that the
      latter is a far more complicated equation. By contrast, a reversible form of the
      Monod-Wyman-Changeux equation that has sometimes been used leads to predictions
      for the effects of modifiers at high substrate concentration that differ
      qualitatively from those given by the Adair equation.

PMID- 9283753
TI  - Introduction of a distance cut-off into structural alignment by the double
      dynamic programming algorithm.
AB  - Two approximations were introduced into the double dynamic programming algorithm,
      in order to reduce the computational time for structural alignment. One of them
      was the so-called distance cut-off, which approximately describes the structural
      environment of each residue by its local environment. In the approximation, a
      sphere with a given radius is placed at the center of the side chain of each
      residue. The local environment of a residue is constituted only by the residues
      with side chain centers that are present within the sphere, which is expressed by
      a set of center-to-center distances from the side chain of the residue to those
      of all the other constituent residues. The residues outside the sphere are
      neglected from the local environment. Another approximation is associated with
      the distance cut-off, which is referred to here as the delta N cut-off. If two
      local environments are similar to each other, the numbers of residues
      constituting the environments are expected to be similar. The delta N cut-off was
      introduced based on the idea. If the difference between the numbers of the
      constituent residues of two local environments is greater than a given threshold
      value, delta N, the evaluation of the similarity between the local environments
      is skipped. The introduction of the two approximations dramatically reduced the
      computational time for structural alignment by the double dynamic programming
      algorithm. However, the approximations also decreased the accuracy of the
      alignment. To improve the accuracy with the approximations, a program with a two
      step alignment algorithm was constructed. At first, an alignment was roughly
      constructed with the approximations. Then, the epsilon-suboptimal region for the
      alignment was determined. Finally, the double dynamic programming algorithm with
      full structural environments was applied to the residue pairs within the epsilon
      suboptimal region to produce an improved alignment.

PMID- 9283754
TI  - Meta-MEME: motif-based hidden Markov models of protein families.
AB  - MOTIVATION: Modeling families of related biological sequences using Hidden Markov
      models (HMMs), although increasingly widespread, faces at least one major
      problem: because of the complexity of these mathematical models, they require a
      relatively large training set in order to accurately recognize a given family.
      For families in which there are few known sequences, a standard linear HMM
      contains too many parameters to be trained adequately. RESULTS: This work
      attempts to solve that problem by generating smaller HMMs which precisely model
      only the conserved regions of the family. These HMMs are constructed from motif
      models generated by the EM algorithm using the MEME software. Because motif-based
      HMMs have relatively few parameters, they can be trained using smaller data sets.
      Studies of short chain alcohol dehydrogenases and 4Fe-4S ferredoxins support the
      claim that motif-based HMMs exhibit increased sensitivity and selectivity in
      database searches, especially when training sets contain few sequences.

PMID- 9283755
TI  - Visual BLAST and visual FASTA: graphic workbenches for interactive analysis of
      full BLAST and FASTA outputs under MICROSOFT WINDOWS 95/NT.
AB  - MOTIVATION: When routinely analysing protein sequences, detailed analysis of
      database search results made with BLAST and FASTA becomes exceedingly time
      consuming and tedious work, as the resultant file may contain a list of hundreds
      of potential homologies. The interpretation of these results is usually carried
      out with a text editor which is not a convenient tool for this analysis. In
      addition, the format of data within BLAST and FASTA output files makes them
      difficult to read. RESULTS: To facilitate and accelerate this analysis, we
      present for the first time, two easy-to-use programs designed for interactive
      analysis of full BLAST and FASTA output files containing protein sequence
      alignments. The programs, Visual BLAST and Visual FASTA, run under Microsoft
      Windows 95 or NT systems. They are based on the same intuitive graphical user
      interface (GUI) with extensive viewing, searching, editing, printing and
      multithreading capabilities. These programs improve the browsing of BLAST/FASTA
      results by offering a more convenient presentation of these results. They also
      implement on a computer several analytical tools which automate a manual
      methodology used for detailed analysis of BLAST and FASTA outputs. These tools
      include a pairwise sequence alignment viewer, a Hydrophobic Cluster Analysis plot
      alignment viewer and a tool displaying a graphical map of all database sequences
      aligned with the query sequence. In addition. Visual Blast includes tools for
      multiple sequence alignment analysis (with an amino acid patterns search engine),
      and Visual FASTA provides a GUI to the FASTA program.

PMID- 9283756
TI  - Prediction of protein secondary structure using the 3D-1D compatibility
      algorithm.
AB  - A new method for the prediction of protein secondary structure is proposed, which
      relies totally on the global aspect of a protein. The prediction scheme is as
      follows. A structural library is first scanned with a query sequence by the 3D-1D
      compatibility method developed before. All the structures examined are sorted
      with the compatibility score and the top 50 in the list are picked out. Then, all
      the known secondary structures of the 50 proteins are globally aligned against
      the query sequence, according to the 3D-1D alignments. Prediction of either alpha
      helix, beta strand or coil is made by taking the majority among the observations
      at each residue site. Besides 325 proteins in the structural library, 77 proteins
      were selected from the latest release of the Brookhaven Protein Data Bank, and
      they were divided into three data sets. Data set 1 was used as a training set for
      which several adjustable parameters in the method were optimized. Then, the final
      form of the method was applied to a testing set (data set 2) which contained
      proteins of chain length < or = 400 residues. The average prediction accuracy was
      as high as 69% in the three-state assessment of alpha, beta and coil. On the
      other hand, data set 3 contains only those proteins of length > 400 residues, for
      which the present method would not work properly because of the size effect
      inherent in the 3D-1D compatibility method. The proteins in data set 3 were,
      therefore, subdivided into constituent domains (data set 4) before being fed into
      the prediction program. The prediction accuracy for data set 4 was 66% on
      average, a few percent lower than that for data set 2. Possible causes for this
      discrepancy are discussed.

PMID- 9283757
TI  - Objectively judging the quality of a protein structure from a Ramachandran plot.
AB  - MOTIVATION: Statistical methods that compare observed and expected distributions
      of experimental observables provide powerful tools for the quality control of
      protein structures. The distribution of backbone dihedral angles ('Ramachandran
      plot') has often been used for such quality control, but without a firm
      statistical foundation. RESULTS: A new and-simple method is presented for judging
      the quality of a protein structure based on the distribution of backbone dihedral
      angles. Inputs to the method are 60 torsion angle distributions extracted from
      protein structures solved at high resolution; one for each combination of residue
      type and tri-state secondary structure. Output for a protein is a Ramachandran Z
      score, expressing the quality of the Ramachandran plot relative to current state
      of-the-art structures.

PMID- 9283758
TI  - Micado--a network-oriented database for microbial genomes.
AB  - MOTIVATION: We created Micado, a database for managing genomic information, as
      part of the Bacillus subtilis genome programs. Its content will be progressively
      extended to the whole microbial world. RESULTS: A relational schema is defined
      for selective queries. It links eubacterial and archaeal sequences, genetic maps
      for Bacillus subtilis and Escherichia coli, and information on mutants. The
      latter comes from a new functional analysis project of unknown genes in B
      subtilis, and the database allows the community to curate information. To help
      queries from users, a graphical interface is built on SQL access to the database
      and provided through the WWW. We have automated imports of microbial sequences,
      and E. coli genetic map, by programming parsers of flat file distributions. These
      ensure smooth updates from molecular biology repositories on the Internet.
      Hyperlinks are created as a complement, to reference other general and
      specialized related information resources.

PMID- 9283759
TI  - A computer program for the analysis of protein complex formation.
AB  - MOTIVATION: We needed an efficient way to explore the binding reactions leading
      to protein complexes of known composition and structure. RESULTS: A new program
      is described that allows the user to define a set of protein elements and to link
      these elements into an oligomeric 'ball-and-stick' assembly in a graphical
      interface. Once the structure of the oligomer has been defined, the program then
      employs a novel algorithm to deduce the binding reactions and intermediate
      complexes needed to make the oligomer from its starting protein components. The
      program also finds the equilibrium state of the system, using either default
      starting concentrations and Kd values or data supplied by the user.

PMID- 9283760
TI  - DISTREE: a tool for estimating genetic distances between aligned DNA sequences.
AB  - MOTIVATION: Substitution rates estimated from aligned DNA data can be used as
      genetic distances to investigate the phylogenetic relationship of those
      sequences. For this purpose, a Markov model of nucleotide substitution has to be
      assumed that describes this process most adequately. RESULTS: A program is
      presented that estimates substitution rates and their standard errors for a
      variety of Markov models. The model introduced by Hasegawa et al. (J. Mol. Evol.,
      22, 160-174, 1985) is the only one for which distances and standard deviations
      need to be calculated numerically, since analytical formulae cannot be derived.
      Each model is implemented in two different variants: (i) assuming rate
      homogeneity or (ii) starting from Gamma-distributed substitution rates across
      sequence sites. The estimation of heterogeneous substitution rates is based on a
      method suggested by Tamura and Nei (Mol. Biol. Evol., 10, 512-526, 1993). All
      required parameters are estimated from sequence data, hence the user is not asked
      to supply any additional input. One goal of the program is to support the user
      when choosing a particular model that describes most adequately the evolution of
      the given data set. For this purpose, a more detailed analysis of this model fit
      is provided. Phylogenetic trees reconstructed from the inferred distances using
      the neighbor-joining algorithm are also available.

PMID- 9283761
TI  - A new dynamic tool to perform assembly of expressed sequence tags (ESTs).
AB  - MOTIVATION: Expressed Sequence Tags (ESTs) are short single-pass DNA sequences
      obtained from either ends of cDNA clones. To exploit these sequences efficiently,
      a dynamic Web-tool has been developed which uses these data to perform fast
      virtual cloning of cDNAs. RESULTS: Starting with a query sequence, the user is
      able to identify related ESTs and extend the sequence of interest step by step,
      possibly to a full-length transcript. Graphical views of the clustering are used
      to monitor the progress of a particular 'cloning' project. Potential open reading
      frames are detected by positional base preference, and hyperlinks to other
      Worldwide Web sites allows the user to retrieve information relevant to each EST
      in a cluster (e.g. sequence traces, clone size, plate position). Apart from cDNA
      cloning, this tool also provides a mechanism for collating gene families and
      polymorphism sites.

PMID- 9283762
TI  - Predicting RNA H-type pseudoknots with the massively parallel genetic algorithm.
AB  - MOTIVATION: Using the genetic algorithm (GA) for RNA folding on a massively
      parallel supercomputer, MasPar MP-2 with 16,384 processors, we successfully
      predicted the existence of H-type pseudoknots in several sequences. RESULTS: The
      GA is applied to folding the tRNA-like 3' end of turnip yellow mosaic virus
      (TYMV) RNA sequence with 82 nucleotides, the 3' UTRs of satellite tobacco
      necrosis virus (STNV)-2 RNA sequence with 619 nucleotides and STNV-I RNA sequence
      with 622 nucleotides, and the bacteriophage T2, T4 and T6 gene 32 mRNA sequences
      with 946, 1340 and 946 nucleotides, respectively. The GA's results match the
      phylogenetically supported tertiary structures of these sequences.

PMID- 9283763
TI  - DSC: public domain protein secondary structure predication.

PMID- 9283764
TI  - JaMBW 1.1: Java-based Molecular Biologists' Workbench.

PMID- 9283765
TI  - EST_GENOME: a program to align spliced DNA sequences to unspliced genomic DNA.

PMID- 9283766
TI  - Calculation of daylength.

PMID- 9283767
TI  - Sequence analysis of the Methanococcus jannaschii genome and the prediction of
      protein function.

PMID- 9283769
TI  - The sulfites: Part III. Facts about sulfites.

PMID- 9283768
TI  - A simple method for sizing large fragments of bacterial DNA separated by PFGE.

PMID- 9283770
TI  - Xeroderma pigmentosum.

PMID- 9283771
TI  - Sporotrichosis: a case report and successful treatment with itraconazole.
AB  - We report the case of a 51-year-old man who presented with a six-month history of
      a slowly growing plaque on the right ring finger and nodules over the right arm.
      Cultures grew Sporothrix schenckii. He was treated with itraconazole, 100 mg
      daily, with complete resolution of the lesions after five months of therapy. The
      differential diagnoses and the various modalities of treatment are emphasized.

PMID- 9283772
TI  - Lawrence-Seip syndrome: report of a case from Egypt.
AB  - A case of acquired total lipodystrophy (Lawrence-Seip syndrome) is reported in a
      17-year-old Egyptian girl. The patient had generalized lipodystrophy, eruptive
      xanthomas, diabetes mellitus, and severe osteoporosis.

PMID- 9283774
TI  - Submandibular abscess caused by Eikenella corrodens.
AB  - Eikenella corrodens is a slow-growing, facultative, anaerobic, gram-negative
      bacillus that is part of the normal oral flora and is found in dental plaque. It
      has become increasingly recognized as a pathogen in nonimmunocompromised and
      immunocompromised hosts. A case of a submandibular abscess due to Eikenella
      corrodens, which was successfully treated by administration of cefuroxime
      accompanied by incision and drainage, is presented. Dermatologists need to be
      aware of this pathogen is the evaluation of suppurative lesions of the head and
      neck.

PMID- 9283773
TI  - Capnocytophaga canimorsus septicemia in an asplenic patient.
AB  - We present a classic case of Capnocytophaga canimorsus septicemia. C. canimorsus
      (from the Latin canis, dog; and morsus, a bite), formerly called CDC group DF-2,
      is a gram-negative rod that typically causes septicemia with disseminated
      intravascular coagulation in both immunocompromised and immunocompetent hosts.

PMID- 9283775
TI  - To burn or not to burn: use of computer-enhanced stimuli to encourage application
      of sunscreens.
AB  - Skin cancer affects 515,000 Americans every year, causing more than 7,000 deaths.
      Prior studies attempted, with scant success, to increase general knowledge about
      protection of the skin and to encourage use of sunscreens. The failure was
      attributed to the allure of the suntan as a symbol of health and affluence and to
      the "optimistic bias" (belief in one's own invulnerability) displayed by
      sunbathers. The study detailed here sought to increase the use by subjects of
      sunscreen by showing computer-altered images of their own faces, aged and
      disfigured by lesions. That stimulus was designed to counter false impressions
      and illusions of sunbathers about the benefits of the sun by demonstrating,
      immediately and personally, negative effects of sun exposure. Data were collected
      from thirty adolescents in the form of six weekly logs of sunscreen use and time
      spent outdoors between 10 AM and 3 PM. Results showed that the computer-altered
      images motivated increased use of sunscreen in the short term: subjects in the
      experimental groups used sunscreen almost three times as frequently as those in
      the control group during the experimental period (P = 0.000). Images of aging and
      disfiguring by lesions produced a more intense and prolonged modification in
      behavior than images of aging only.

PMID- 9283776
TI  - Treatment of diabetic ketoacidosis using normalization of blood 3-hydroxybutyrate
      concentration as the endpoint of emergency management. A randomized controlled
      study.
AB  - OBJECTIVE: To compare the efficacy of an extended insulin regimen using
      correction of hyperketonemia as endpoint with a more conventional regimen in the
      treatment of diabetic ketoacidosis. RESEARCH DESIGN AND METHODS: A total of 22
      patients admitted to a Belfast teaching hospital with clinical and biochemical
      features of diabetic ketoacidosis (pH < 7.25 and/or bicarbonate < 16 mmol/l) were
      randomized to either conventional or extended insulin regimens. In the
      conventional regimen, insulin was administered at 5 U/h until near-normoglycemia
      (blood glucose < or = 10 mmol/l) and then administered at a reduced rate until
      clinical recovery. In the extended regimen, administration of insulin at 5 U/h
      was continued beyond attainment of normoglycemia, until resolution of
      hyperketonemia (3-hydroxybutyrate < 0.5 mmol/l). Main outcome measures were 3
      hydroxybutyrate and bicarbonate levels during the 24 h after attainment of near
      normoglycemia. RESULTS: After near-normoglycemia, correction of hyperketonemia
      was achieved earlier with the extended treatment (5.9 +/- 0.8 vs. 21.8 +/- 3.4 h,
      P = 0.0004 [mean +/- SD]). The area under the curve of 3-hydroxybutyrate against
      time for 24 h after near-normoglycemia was reduced with the extended treatment
      (24.9 +/- 3.8 vs. 55.9 +/- 6.7 mmol.l-1.h-1, P = 0.001). These differences
      remained statistically significant after adjustment for higher baseline levels of
      3-hydroxybutyrate at near-normoglycemia in the extended treatment group.
      Bicarbonate levels at 6 and 12 h after near-normoglycemia were not significantly
      different between groups. CONCLUSIONS: The extended insulin regimen, which was
      easy to implement at ward level, produced a more rapid resolution of ketosis than
      the conventional regimen.

PMID- 9283777
TI  - Induction of long-term glycemic control in newly diagnosed type 2 diabetic
      patients by transient intensive insulin treatment.
AB  - OBJECTIVE: Type 2 diabetes is a slowly progressive disease, in which the gradual
      deterioration of glucose tolerance is associated with the progressive decrease in
      beta-cell function. Hyperglycemia per se has deleterious effects on both beta
      cell function and insulin action, which are partially reversible by the short
      term control of blood glucose levels. We hypothesized that the induction of
      euglycemia, using intensive insulin therapy at the time of clinical diagnosis,
      could lead to a significant improvement in insulin secretion and action and thus
      alter the clinical course of the disease. RESEARCH DESIGN AND METHODS: Thirteen
      newly diagnosed diet-unresponsive type 2 diabetic patients were treated with
      continuous subcutaneous insulin infusion (CSII) for 2 weeks and followed
      longitudinally while being treated with diet alone. RESULTS: Four patients were
      considered therapeutic failures since CSII failed to induce euglycemia (n = 1) or
      glucose control deteriorated within 6 months after CSII (n = 3). The remaining
      nine patients were maintained on diet alone with adequate control from 9 to > 50
      months (median +/- SE, 26 +/- 4.8 months). In five patients, glycemic control
      deteriorated after 9-36 months, but a repeat 2-week CSII treatment reestablished
      control in four patients. One of these patients underwent a third CSII treatment
      13 months later. At the time this article was written, six patients of the
      initial group were still controlled without medication 16-59 months (median +/-
      SE, 45.5 +/- 6.6 months) after the initiation of treatment. Body weight remained
      unchanged in all patients. CONCLUSIONS: These findings suggest that in a
      significant proportion of type 2 diabetic patients who fail to respond to dietary
      measures, short-term intensive insulin treatment can effectively establish
      responsiveness, allowing long-term glycemic control without medication. Further
      studies are required to establish whether simpler treatment regimens could be
      equally effective. If the hypothesis offered here finds support, present
      approaches to the management of newly diagnosed type 2 diabetes may need to be
      revised.

PMID- 9283778
TI  - Lispro analog for treatment of generalized allergy to human insulin.
AB  - OBJECTIVE: To evaluate the clinical usefulness of the human insulin analog lispro
      in a patient with generalized allergy to human insulin. RESEARCH DESIGN AND
      METHODS: A 34-year-old obese female patient developed systemic allergic reactions
      to human insulin but tolerated insulin lispro. Sequential analyses of the anti
      insulin IgE and IgG immunoglobulins were performed. RESULTS: On intradermal test,
      the lispro insulin produced a 50% less intense wheal-flare response, compared
      with human insulin, which was presumed to be due to lispro's molecular form. The
      intradermal reactivity to both human and lispro insulins decreased with time and
      disappeared by week 25. 125I-labeled lispro and human insulin binding antibody
      titers of both the IgE and IgG immunoglobulins were high initially, but decreased
      progressively, becoming very low by the end of 1 year. In in vitro immunoassay,
      the lispro and human insulins show a complete cross-reactivity. CONCLUSIONS:
      Lispro may be useful for the management of allergy to human insulin. This analog
      of human insulin appears to have a reduced immunogenic potency.

PMID- 9283779
TI  - Comparison of a neurothesiometer and vibration in measuring vibration perception
      thresholds and relationship to nerve conduction studies.
AB  - OBJECTIVE: To compare vibration perception thresholds (VPTs) obtained with two
      different instruments, a neurothesiometer and a vibratron, and to characterize
      variability of repeat measures and correlation with sural nerve conduction
      parameters. RESEARCH DESIGN AND METHODS: A total of 152 patients with diabetic
      peripheral neuropathy received electrodiagnostic evaluation and quantitative VPT
      testing with the Vibratron II and the Horwell Neurothesiometer. Of the patients,
      42 returned for repeat nerve conduction studies and VPT testing with both types
      of equipment on three separate occasions. RESULTS: The variability of repeat
      testing for the vibratron was 34 and 31% in the right and left first toes,
      respectively. Variability for neurothesiometer was 8 and 6% for the right and
      left toes. This variability compares with that of sural nerve conduction velocity
      of 2% and that of sural nerve amplitude of 8% in this series of patients.
      CONCLUSIONS: We conclude that VPT determined with the neurothesiometer is less
      variable than with the vibratron and more reflective of peripheral nerve
      function. Our results indicate that the neurothesiometer can be used reliably in
      clinical research trials.

PMID- 9283781
TI  - Maternal serum ferritin and gestational impaired glucose tolerance.
AB  - OBJECTIVE: To determine if the reported features of decreased iron store in the
      infant of diabetic mother are related to underlying maternal iron deficiency, a
      prospective case-control study was performed on a group of low-risk antenatal
      patients without preexisting anemia or thalassemia trait and before the diagnosis
      of gestational diabetes mellitus (GDM) in the last trimester. RESEARCH DESIGN AND
      METHODS: At the time of routine screening for anemia and GDM at 28-30 weeks of
      gestation, an additional blood sample was collected for the assay of serum
      ferritin, iron, and total iron binding capacity (TIBC). Patients with elevated
      random sugar underwent a 75-g oral glucose tolerance test (OGTT), interpreted by
      the World Health Organization criteria. For each person diagnosed with GDM, a
      control subject matched in maternal age and parity was identified, and their iron
      status and hematological indexes were compared. RESULTS: There were 60 patients
      with gestational impaired glucose tolerance (GIGT), and none had frank GDM. There
      was no difference in the hematological indexes or serum iron and TIBC values, but
      serum ferritin level was significantly increased in the GIGT group, when compared
      with control subjects. CONCLUSIONS: The findings indicate that there was no
      evidence of preexisting iron deficiency in the third trimester before the
      diagnosis of GIGT, while serum ferritin was even increased in the GIGT patients,
      a phenomenon that could have reflected the glucose intolerance. Serum ferritin is
      probably an unreliable index for maternal iron therapy in these patients, and the
      role of iron therapy in GIGT patients remains to be established.

PMID- 9283780
TI  - ACE inhibitor use is associated with hospitalization for severe hypoglycemia in
      patients with diabetes. DARTS/MEMO Collaboration. Diabetes Audit and Research in
      Tayside, Scotland. Medicines Monitoring Unit.
AB  - OBJECTIVE: To evaluate the association between the use of ACE inhibitors and
      hospital admission for severe hypoglycemia and to explore the effects of
      potential confounding variables on this relationship. RESEARCH DESIGN AND
      METHODS: The association between the use of ACE inhibitors and the incidence of
      hypoglycemia is controversial. A recent study reported that 14% of all hospital
      admissions for hypoglycemia might be attributable to ACE inhibitors. We performed
      a nested case-control study, using a cohort of 6,649 diabetic patients taking
      insulin or oral antidiabetic drugs, on the Diabetes Audit and Research in
      Tayside, Scotland (DARTS) database. From 1 January 1993 to 30 April 1994, we
      identified 64 patients who had been admitted to Tayside hospitals with
      hypoglycemia and selected 440 control patients from the same cohort. RESULTS:
      Hypoglycemia was associated with the use of ACE inhibitors (odds ratio [OR] 3.2,
      95% CI 1.2-8.3, P = 0.023), whereas use of beta-blockers and calcium antagonists
      was not associated with an increased risk of hospitalization for hypoglycemia
      with ORs of 0.9 (95% CI 0.3-3.3) and 1.7 (95% CI 0.2-2.1), respectively. There
      were significant differences between case and control patients in type of
      diabetes treatment, diabetes duration, place of routine diabetes care, and
      congestive cardiac failure. These differences did not confound the relationship
      between ACE inhibitors and hypoglycemia (adjusted OR 4.3, 95% CI 1.2-16.0).
      CONCLUSIONS: The results show that the association between ACE inhibitor therapy
      and hospital admission for severe hypoglycemia is not explained by these
      confounding factors. Although ACE inhibitors have distinct advantages over other
      antihypertensive drugs in diabetes, the risk of hypoglycemia should be
      considered.

PMID- 9283782
TI  - Effects of a behavioral intervention on treatment adherence and stress management
      in adolescents with IDDM.
AB  - OBJECTIVE: To evaluate the effects of a behavioral program to increase treatment
      adherence and to improve stress management in adolescents with IDDM. RESEARCH
      DESIGN AND METHODS: A quasi-experimental pretest-posttest design with a
      nonequivalent control group was used. Eighteen subjects were assigned to the
      experimental group, which received the program, while nineteen subjects made up
      the control group, which received routine medical care. During the 12
      intervention sessions with diabetic adolescents, different procedures were
      applied: instruction, blood glucose discrimination training, role-playing,
      relaxation exercises, self-instructions, problem-solving strategies, and
      homework, among others. RESULTS: The results show significant changes in the
      experimental group in variables related to diabetes information (patients and
      their parents), adherence, daily hassles, uneasiness and likelihood of response
      in social interactions, skills and frequency of glycemic analyses, blood glucose
      estimate errors, and negative family support (parents). The program had no effect
      on either dietary and physical exercise or glycemic control. The improvements,
      which were maintained at a follow-up carried out 13 months after finishing the
      program, were: patients' information about physiopathology (P = 0.000), diet (P =
      0.000), physical exercise (P = 0.048), glucose testing (P = 0.030), and insulin
      (P = 0.000), barriers to adherence frequency (P = 0.000), severity of daily
      hassles (P = 0.006), and degree of uneasiness in social interaction (P = 0.000).
      CONCLUSIONS: This research introduces the novelty of integrating several
      behavioral procedures within a wide-ranging package that affects aspects implied
      in diabetes control such as treatment adherence and stress management. The
      testing of similar programs on samples of subjects with glycemic control
      difficulties would be useful.

PMID- 9283783
TI  - The insulin resistance syndrome in native Hawaiians. Native Hawaiian Health
      Research (NHHR) Project.
AB  - OBJECTIVE: To investigate whether fasting hyperinsulinemia is associated with a
      clustering of cardiovascular disease (CVD) risk factors, manifesting as the
      insulin resistance syndrome (IRS), in a population of native Hawaiians. RESEARCH
      DESIGN AND METHODS: A total of 574 native Hawaiians > or = 30 years of age were
      examined for blood pressure, waist-to-hip ratio (WHR), BMI, oral glucose
      tolerance, and fasting lipid, insulin, and C-peptide concentrations. All
      statistical analyses (n = 384) excluded 190 individuals who had NIDDM or who were
      taking hypertension medication. Using logistic regression analysis, fasting
      insulin and C-peptide levels were compared with CVD risk factors (glucose
      intolerance, hypertension, central adiposity, elevated triglyceride levels, and
      low HDL cholesterol levels) after adjusting for age and obesity. RESULTS: Sixty
      six percent of native Hawaiians were overweight or obese, and 70% were found to
      have central adiposity. Fasting insulin concentrations were correlated with BMI,
      WHR, blood pressure, and triglyceride, HDL cholesterol, and glucose
      concentrations. Fasting insulin was also significantly associated with an
      increasing number of CVD risk factors in each participant (P < 0.001). Fasting
      insulin and C-peptide concentrations were independently associated with glucose
      intolerance, high triglyceride levels, and low HDL cholesterol levels. However,
      only fasting C-peptide concentrations were independently associated with
      hypertension and central adiposity. Apparent differences in the correlates of
      fasting insulin and C-peptide may be related to multiple factors and warrant
      further evaluation. CONCLUSIONS: This study provides cross-sectional data
      confirming the existence of the IRS in native Hawaiians. However, further
      longitudinal studies are needed to examine the relationship of insulin resistance
      and/or surrogate markers to increased rates of NIDDM and CVD mortality in native
      Hawaiians.

PMID- 9283784
TI  - Coronary artery disease in diabetic patients with lower-extremity arterial
      disease: disease characteristics and survival. A report from the Coronary Artery
      Surgery Study (CASS) registry.
AB  - OBJECTIVE: Patients who have diabetes and lower-extremity arterial disease (LEAD)
      are at an increased risk of dying from coronary artery disease (CAD). This study
      was undertaken to: 1) define the clinical and arteriographic factors associated
      with LEAD among diabetic patients; 2) determine the long-term survival and
      predictors of mortality of diabetic patients with LEAD, compared to those without
      LEAD; and 3) determine if the presence of LEAD is an independent risk factor for
      mortality among diabetic patients with CAD. RESEARCH DESIGN AND METHODS: A total
      of 263 diabetic patients from the Coronary Artery Surgery Study (CASS) registry
      with LEAD, who were > or = 50 years of age, and who had arteriographically proven
      CAD, were identified and followed for a mean of 12.8 years. A total of 1,349
      comparably aged diabetic patients from the CASS registry with CAD and no evidence
      of LEAD were followed for an equivalent period of time. RESULTS: Compared with
      diabetic patients without LEAD, diabetic patients with LEAD were characterized by
      the presence of cerebrovascular disease, a high rate of current smoking, elevated
      systolic blood pressure, high grades of angina pectoris, and digitalis use.
      Severity of epicardial CAD and extent of CAD were not independent predictors of
      the presence of LEAD. On follow-up, diabetic patients with LEAD had significantly
      higher mortality (mostly cardiovascular) than diabetic patients without LEAD,
      with a median survival of 8.1 and 10.9 years, respectively. On multivariate
      analysis, age, the number of significantly narrowed coronary arteries, and the
      presence of left ventricular dysfunction predicted mortality in both subsets of
      diabetic patients. Among all the diabetic patients with CAD, the presence of LEAD
      was an independent risk factor for mortality. CONCLUSIONS: Diabetic patients with
      LEAD have a higher mortality rate (mostly cardiovascular) than diabetic patients
      without LEAD, despite no apparent anatomic differences in the severity and extent
      of CAD. This suggests that factors associated with the presence of LEAD, other
      than the anatomy of the coronary circulation, may play a role in determining
      survival among diabetic patients with LEAD and CAD.

PMID- 9283786
TI  - Excess costs of medical care for patients with diabetes in a managed care
      population.
AB  - OBJECTIVE: To estimate the excess costs of medical care for patients with
      diabetes in a managed care population and to determine the proportion of costs
      spent on treating the complications of diabetes. RESEARCH DESIGN AND METHODS: A
      comparison of 1-year (1994) costs of medical care in the 85,209 members of the
      diabetes registry of Kaiser Permanente, Northern California, and in 85,209 age-
      and sex-matched nondiabetic control subjects. Costs were obtained from automated
      program databases. Costs specifically related to treating acute and long-term
      complications of diabetes were identified, and the excess costs attributable to
      each complication in individuals with diabetes were calculated. RESULTS: Excess
      expenditures in individuals with diabetes totaled $282.7 million, or $3,494 per
      person. Per person expenditures for members with diabetes were 2.4 times those
      for matched control subjects. The largest proportion of total excess costs was
      for hospitalizations within the health maintenance organization (38.5%). Nearly
      38% of the total excess was spent treating the long-term complications of
      diabetes, predominantly coronary heart disease and end-stage renal disease.
      CONCLUSIONS: Diabetes is a costly condition by virtue of its high prevalence and
      high per person costs. A large proportion of these costs are related to treating
      complications of diabetes. Available evidence indicates that several measures can
      reduce complication rates. Thus, effective disease management programs that aim
      to prevent complications could potentially lead to cost savings in managed care
      settings.

PMID- 9283785
TI  - NIDDM and blood pressure as risk factors for poor cognitive performance. The
      Framingham Study.
AB  - OBJECTIVE: To determine if NIDDM and blood pressure are risk factors for poor
      cognitive performance and if history and duration of NIDDM and blood pressure
      interact such that the risk of poor performance is greater for subjects with both
      NIDDM and hypertension. RESEARCH DESIGN AND METHODS: We used a large prospective
      cohort sample with 187 NIDDM subjects and 1,624 nondiabetic subjects who were
      followed for 28-30 years. Cognitive function was assessed using eight tests of
      learning, memory, visual organization, verbal fluency attention, concept
      formation, and abstract reasoning. A composite score was also calculated. Odds
      ratios were used to estimate the relative risk of performing below the lower 25th
      percentile of z scores on these tests. RESULTS: NIDDM and blood pressure
      interacted such that diagnosis and duration of NIDDM were associated with greater
      risk of poor performance on tests of visual memory and on the composite score for
      hypertensive subjects. Duration of NIDDM was associated with increased risk for
      poor performance on tests of verbal memory and concept formation. Insulin-treated
      NIDDM subjects were at higher risk for poor cognitive performance than those
      NIDDM subjects treated with oral agents or diet. Blood pressure level was
      associated independently with a measure of verbal fluency. CONCLUSIONS: History
      and duration of NIDDM and high blood pressure are significant risk factors for
      poor cognitive performance. Hypertensive people with NIDDM are at greatest risk
      for poor performance on tests measuring visual organization and memory.

PMID- 9283787
TI  - Evaluation of ICA512As in combination with other islet cell autoantibodies at the
      onset of IDDM.
AB  - OBJECTIVE: The ICA512 pancreatic islet autoantigen is a putative tyrosine
      phosphatase that is co-identified with the earlier described 40-kDa autoantigen.
      We report the frequency of autoantibodies to islet cell antigen 512 (ICA512As) in
      recent-onset IDDM and compare this with other islet cell autoantibodies,
      including those to GAD (GADAs), insulin (IAAs), and islet cell cytoplasm (ICAs)
      identified by immunofluorescence. RESEARCH DESIGN AND METHODS: Sera from 232
      children aged between 9 months and 14.9 years collected within 14 days of
      diagnosis were tested for ICA512As by a radioimmunoprecipitation assay. The
      results were compared with previously reported data for GADAs (n = 232), IAAs (n
      = 167), and ICAs (n = 230). RESULTS: The frequency of a positive result for
      ICA512As in children with newly diagnosed IDDM was 60%. The frequency was greater
      for children with an age of onset between 5 and 10 years (69%) than for children
      aged < 5 years (49%) and aged between 10 and 15 years (56%). The frequencies for
      other autoantibody reactivities were 69% for GADAs, 65% for IAAs, and 70% for
      ICAs. A combination of positive results for ICA512As, GADAs, and IAAs gave a
      sensitivity for the diagnosis of childhood IDDM of 95%, which was not
      significantly increased by a positive result for ICAs (96%). CONCLUSIONS: Our
      results further establish that positivity in a combination of tests is more
      valuable for the prediction of IDDM than a result for any single autoantibody and
      that the age of the patient should be considered when selecting the combination
      of tests to use.

PMID- 9283788
TI  - Serum immunoreactive leptin concentrations in a Canadian aboriginal population
      with high rates of NIDDM.
AB  - OBJECTIVE: To better understand the relationship between leptin and the
      anthropometric and physiological variables associated with diabetes, we measured
      this protein in an isolated Canadian aboriginal population with very high rates
      of NIDDM. RESEARCH DESIGN AND METHODS: There were 728 individuals aged 10-79
      years who participated in a population-based survey to determine the prevalence
      of NIDDM and its associated risk factors. Fasting blood samples for glucose,
      insulin, triglyceride, and leptin were collected; a 75-g oral glucose tolerance
      test was administered and a second blood sample drawn after 120 min. Height,
      weight, and waist and hip circumference were determined, and percent body fat was
      estimated using biological impedance analysis. Fitness level was assessed in a
      subsample of individuals using a validated submaximal step test. The relationship
      between serum leptin and the other variables was assessed using Spearman's
      correlation coefficients and multiple linear regression. RESULTS: Serum leptin
      concentration was strongly correlated with adiposity, and levels were
      substantially higher in female subjects in all age-groups. For male subjects,
      percent body fat, fasting insulin level, and waist circumference were significant
      independent predictors of log serum leptin concentration in a multiple linear
      regression model (R2 = 0.582). For female subjects, these variables plus glucose
      tolerance status were included in the final model (R2 = 0.633). Fitness level,
      when included with the main effects of the above models, was a significant
      predictor for male subjects only. CONCLUSIONS: In an isolated aboriginal
      community with high rates of diabetes, we found significant independent
      relationships between leptin and percent body fat and between leptin and fasting
      insulin. As documented in other populations, the higher leptin concentration
      among female subjects may reflect differential leptin production from different
      adipose tissue beds, or leptin resistance. Independent relationships also existed
      among leptin and glucose tolerance status in female subjects and fitness level in
      male subjects.

PMID- 9283789
TI  - Power spectral analysis of heart rate variability in children and adolescents
      with IDDM.
AB  - OBJECTIVE: To investigate power spectral analysis (PSA) of heart rate variability
      (HRV) in children and adolescents with IDDM, its relationship with other measures
      of HRV and standard cardiovascular responses, and factors associated with reduced
      HVR. RESEARCH DESIGN AND METHODS: A total of 130 subjects with IDDM aged 12.8 +/-
      3.2 years and 108 healthy control subjects were studied. Power spectra were
      analyzed from supine electrocardiograph (ECG) recordings by processing into
      consecutive R-R intervals and analysis using fast Fourier transformation.
      Standard cardiovascular responses to deep breathing and standing were performed.
      RESULTS: IDDM subjects had a reduction in total power including both low
      frequency (0.05-0.14 Hz; P = 0.0001) and high-frequency (0.14-0.40 Hz; P =
      0.0002) components. These changes were seen from diagnosis. Other measures of
      HRV, coefficient of variation (CV) and standard deviation (SD) of mean resting
      heart rate, were also significantly lower in IDDM. All 20 (15%) of the 130 IDDM
      subjects with total power less than the 5th percentile in control subjects also
      had reduced HRV when measured by CV of heart rate. There was an independent
      relationship between age and the high-frequency component in IDDM subjects and
      control subjects. Total power correlated with mean heart rate (r = -0.56; P <
      0.0001), CV of heart rate (r = 0.90; P < 0.00001), SD of heart rate (r = 0.91; P
      < 0.00001), heart rate response to deep breathing (r = 0.45; P < 0.0001), and
      duration in IDDM subjects. There was no correlation with short-term or long-term
      metabolic control. Retesting of 27 subjects showed a variability in total power
      and its components comparable to other measures of HRV and standard heart rate
      responses. CONCLUSIONS: Changes in HRV are a sensitive and reproducible measure
      of early autonomic dysfunction in childhood. In this age-group, PSA appears no
      more sensitive a measure of reduced HRV than other closely correlated measures of
      HRV.

PMID- 9283790
TI  - The epidemiology of diabetes in pregnant Native Canadians. A risk profile.
AB  - OBJECTIVE: The purpose of this study was to determine the prevalence of diabetes
      in pregnancy (gestational diabetes mellitus [GDM] and NIDDM) and to identify risk
      factors in the development of GDM in a native population in northwestern Ontario,
      Canada. RESEARCH DESIGN AND METHODS: A retrospective analysis of 1,305 singleton
      deliveries among Ojibwa-Cree women from northwestern Ontario, Canada, was
      conducted from 1990 to 1993 inclusive. GDM was diagnosed using a 3-h oral glucose
      tolerance test (OGTT) and defined according to standard guidelines. RESULTS: The
      overall prevalence of diabetes in pregnancy (NIDDM and GDM) was 11.6% (152 of
      1,305) with a GDM prevalence of 8.4% (110 of 1,305). Among 741 women with
      complete data, prevalence rates increased with age, peaking at 46.9% in the age
      group > or = 35 years. Significant risk factors for GDM included older maternal
      age, multiparity, prepregnancy obesity, a family history of diabetes, and a
      history of GDM in previous pregnancies. CONCLUSIONS: Diabetes in pregnancy among
      Ojibwa-Cree reported here represent the highest rates reported to date in a
      Canadian population. The high rates of maternal obesity and relative young age of
      this population further highlight the urgent need for diabetes screening and
      prevention in this population.

PMID- 9283791
TI  - Dermal interstitial glucose as an indicator of ambient glycemia.
AB  - OBJECTIVE: Using a novel minimally invasive (< or = 1.4 mm) technique to sample
      minuscule (0.5 microliter) amounts of dermal interstitial fluid (ISF), we
      assessed the accuracy of its glucose concentrations in predicting concurrently
      measured venous plasma and capillary plasma glucose concentrations. RESEARCH
      DESIGN AND METHODS: A total of 67 adult (37 male and 30 female) volunteers (57
      with and 10 without diabetes) with venous plasma glucose levels from 1.6 to 28.4
      mmol/l underwent forearm ISF, antecubetal venous, and fingertip capillary
      sampling. RESULTS: Rank correlations were 0.974 for ISF 1 vs. 2, 0.954 for ISF
      vs. venous, 0.935 for ISF vs. capillary, and 0.987 for venous vs. capillary.
      Median absolute differences were 0.53 mmol/l for ISF 1 vs. 2, 1.33 mmol/l for ISF
      vs. venous, 1.06 mmol/l for ISF vs. capillary, and 0.56 mmol/l for capillary vs.
      venous. Equations expressing ISF glucose as a function of venous and capillary
      glucose and equations expressing capillary glucose as a function of venous
      glucose had slopes of 0.995, 0.936, and 1.021, respectively (none significantly
      different from unity), and intercepts of 1.03 mmol/l (P = 0.024), 0.94 mmol/l (P
      = 0.131), and 0.56 mmol/l (P = 0.041), respectively. Error grid analysis of ISF
      vs. venous glucose and of capillary vs. venous glucose showed that 97% of the
      measurements fell within grids A and B. CONCLUSIONS: Dermal ISF sampling is a
      bloodless minimally invasive technique that provides a medium for glucose
      measurement, the concentrations of which closely reflect ambient glycemia to a
      degree comparable with that of capillary glucose measurements.

PMID- 9283792
TI  - Glibenclamide, but not acarbose, increases leptin concentrations parallel to
      changes in insulin in subjects with NIDDM.
AB  - OBJECTIVE: To hypothesize if glibenclamide, which increases insulin levels, also
      increases leptin concentrations. RESEARCH DESIGN AND METHODS: Leptin is a hormone
      that regulates weight in mice. In obese humans, leptin concentrations are
      increased, suggesting resistance to the effects of this hormone. Although short
      term infusion of insulin during the hyperinsulinemiceuglycemic clamp does not
      increase leptin concentration, the effect of oral antidiabetic agents on leptin
      concentration is unknown. Differing effects can be expected, since glibenclamide
      acts via stimulation of insulin secretion, whereas acarbose inhibits alpha
      glucosidases of the small intestine and has no direct effect on insulin levels.
      We examined the effect of acarbose (n = 4), glibenclamide (n = 6), and placebo (n
      = 6) on insulin and leptin levels during 24-h periods before and after 16 weeks
      of therapy. RESULTS: We observed a significant diurnal variation in leptin
      concentrations. This was inversely related to insulin levels during the 24-h
      follow-up with usual diet. Neither the placebo nor acarbose altered leptin
      concentrations. However, glibenclamide increased leptin concentrations parallel
      to insulin levels. There were only minor changes in body weight during the l6
      week follow-up: decrease in the placebo group (change -0.5 kg/m2, P = 0.07) and
      acarbose (change -0.7 kg/m2, P = 0.046) and increase in the glibenclamide group
      (change 0.8 kg/m2, P = 0.27). However, individual subjects who gained weight had
      increases in their leptin concentrations. The diurnal variation in leptin
      concentrations was preserved after glibenclamide. CONCLUSIONS: Glibenclamide
      increases circadian leptin and insulin concentrations, whereas acarbose does not.
      This observation may help to explain weight gain in subjects treated with
      glibenclamide and stable weight in those treated with acarbose in the long run.

PMID- 9283793
TI  - U.K. Prospective Diabetes Study 22. Effect of age at diagnosis on diabetic tissue
      damage during the first 6 years of NIDDM.
AB  - OBJECTIVE: To assess the effect of age at diagnosis on the initial prevalence and
      subsequent risk of the progression of diabetic tissue damage in patients with
      NIDDM. RESEARCH DESIGN AND METHODS: The prevalence of Q-wave myocardial
      infarction, absent dorsalis pedis pulses, retinopathy, absent ankle jerks,
      hypertension, and microalbuminuria were determined at baseline and at 3 and 6
      years of follow-up in five consecutive 6-year age-cohorts of 3,027 newly
      diagnosed white patients aged between 36 and 65 years recruited to the U.K.
      Prospective Diabetes Study. The effect of age at diagnosis on the initial
      prevalence and the risk of progression of these complications and associated
      conditions was analyzed using logistic regression and proportional odds methods,
      respectively. RESULTS: Q-wave myocardial infarction and hypertension were more
      prevalent in older patients at presentation, but age at diagnosis did not have a
      significant effect on the increased risk of either after 6 years of NIDDM. Absent
      dorsalis pedis pulses and ankle jerks were also more prevalent in the older age
      groups at presentation, but age at diagnosis was a significant predictor of the
      increasing prevalence of both during follow-up. The baseline prevalence of
      retinopathy and microalbuminuria was not related to age. The subsequent risk of
      retinopathy, but not microalbuminuria, increased significantly with age at
      diagnosis. CONCLUSIONS: Age at diagnosis has a variable impact on different types
      of diabetic tissue damage and may thus be an important variable in
      epidemiological and intervention studies in NIDDM. Regular ophthalmologic
      surveillance and examination of the feet increase in importance with increasing
      age since the diagnosis of NIDDM.

PMID- 9283794
TI  - Role of IGF binding protein-1 in the dawn phenomenon and glycemic control in
      children and adolescents with IDDM.
AB  - OBJECTIVE: To clarify the involvement of IGF binding protein (IGFBP)-1 in the
      dawn rise in plasma glucose and in the overall glycemic control in patients with
      IDDM. RESEARCH DESIGN AND METHODS: Seventy patients with IDDM were divided into
      three groups according to pubertal development. Blood samples were obtained for
      measuring plasma glucose, IGFBP-1, and free insulin at 2200, 0500, and 0700 over
      a 2-day period. Levels of HbA1c, IGF-1, and IGFBP-3 were determined at 0700.
      Urinary growth hormone (GH) was collected overnight. To examine its frequency,
      the dawn phenomenon was defined on the basis of the following: 1) change in
      plasma glucose from 0500 to 0700, 2) plasma glucose level at 0700, and 3) no
      antecedent hypoglycemia. RESULTS: There was a statistically significant link
      between the dawn changes in plasma glucose and IGFBP-1 (r = 0.37, P < 0.01). The
      former was not related to the change in free insulin or to the overnight urinary
      GH level. In stepwise regression analyses, plasma glucose at 0700 = 0.03 IGFBP-1
      (P < 0.01) + 0.525 HbA1c (P < 0.01) + 3.696 (R2 = 51%). Approximately half of the
      patients in each group exhibited the dawn phenomenon; 38% of patients with HbA1c
      < 8% also showed the dawn phenomenon. CONCLUSIONS: We have demonstrated a
      statistically significant link between the morning risk in IGFBP-1 and plasma
      glucose. The free fraction of IGF-1 modulated by acute changes in IGFBP-1 may
      play a direct role. The dawn phenomenon may occur regardless of pubertal stage or
      glycemic control in children and adolescents with IDDM.

PMID- 9283795
TI  - The use of biothesiometry to detect neuropathy in children and adolescents with
      IDDM.
AB  - OBJECTIVE: To develop clinically useful reference ranges for vibration perception
      thresholds (VPTs), using biothesiometry in children and adolescents and to assess
      the reliability of the technique to identify subclinical neuropathy in subjects
      with IDDM at this age and to examine a large population-based sample of pediatric
      patients. RESEARCH DESIGN AND METHODS: VPTs were measured using a handheld
      biothesiometer at the medial malleolus and hallux in 232 nondiabetic children and
      adolescents aged 7-18 years (12.9 +/- 4.2 years) and a population-based sample of
      307 young IDDM patients (13.3 +/- 4.6 years of age). The mean of three readings
      at each site was correlated with height, pubertal status, and age for all
      subjects and, in addition for the IDDM sample, with the duration of IDDM, ambient
      blood glucose, and mean HbA1c from diagnosis. Those IDDM subjects found to have
      elevated VPTs (> 97th percentile), and a control group of patients with IDDM
      underwent nerve conduction studies to determine the sensitivity and specificity
      of biothesiometry to detect abnormal neural function in children. Interoperator
      reliability was assessed in a separate trial in which two operators measured VPTs
      independently in the same 11 children. RESULTS: In the nondiabetic control
      subjects, height demonstrated the best correlation with VPT measures, and a
      reference range was thus established with percentile charts, using mean VPT and
      height. VPTs were higher in the diabetic sample, compared with the nondiabetic
      sample (P < 0.05). Of the children, 28 (9.1%) had VPT values > 97th percentile
      developed from studies of the nondiabetic subjects; of these, 11 were younger
      than 11 years and 8 were prepubertal. Nerve conduction studies confirmed reduced
      conduction velocity and prolonged distal latencies in those with abnormal VPTs,
      compared with normal control subjects and IDDM patients with normal VPTs.
      Sensitivity of biothesiometry to reflect abnormal nerve function was estimated as
      82% and specificity as 75% at this age. Interoperator variation was small (7.25%
      of total variance). CONCLUSIONS: Biothesiometry is a useful noninvasive tool for
      the detection of subclinical neuropathy in children and adolescents. The use of
      height-related reference ranges may make screening for neuropathy more feasible
      in younger patients and allow large-scale longitudiral analysis of its
      development.

PMID- 9283796
TI  - Glycosylated hemoglobin level and carotid intimal-medial thickening in
      nondiabetic individuals. The Atherosclerosis Risk in Communities Study.
AB  - OBJECTIVE: People with diabetes are at increased risk for cardiovascular events.
      However, questions remain about what role, if any, homeostatic glucose control
      plays in the development of cardiovascular disease among nondiabetic individuals.
      We investigated the relationship between HbA1c level and carotid intimal-medial
      thickening in normoglycemic individuals. RESEARCH DESIGN AND METHODS: We
      conducted a case-control study among 208 normoglycemic individuals (fasting
      glucose < or = 6.4 mmol/l and no history of diabetes) who had carotid initial
      medial thickening (case subjects) and 208 normoglycemic control subjects
      individually matched for age, sex, race, field center, and date of exam. Subjects
      were free-living men and women, aged 45-64 years at baseline, who participated in
      the Atherosclerosis Risk in Communities (ARIC) Study. RESULTS: HbA1c levels,
      expressed as percent of total hemoglobin, ranged from 4 to 7% and correlated only
      modestly with single measurements of fasting glucose (r = 0.16) and fasting
      insulin (r = 0.14). The mean level of HbA1c was 5.18% among case subjects and
      5.07% among control subjects (P = 0.004, paired t test). As compared with the
      first quartile of HbA1c the matched relative odds of being a case were 1.15,
      1.33, and 2.30 for the second, third, and fourth quartiles, respectively (P =
      0.005 for linear trend). After multivariate adjustment for age, fasting glucose,
      fasting insulin, BMI, smoking status, hypertension, LDL cholesterol, HDL
      cholesterol, fibrinogen, and education level, the respective relative odds
      estimates were 0.98, 1.07, and 1.88 (P = 0.16 for linear trend). When modeled
      linearly as a continuous variable and after adjustment for the above-mentioned
      covariates, a 1% point increment in HbA1c level was associated with 1.77 greater
      odds of being a case (95% CI, 0.9-3.5). CONCLUSIONS: These data provide some
      support to the hypothesis that in the absence of diabetes, homeostatic glycemic
      control is a risk factor for atherosclerosis.

PMID- 9283797
TI  - Lack of change of lipoprotein(a) levels by the optimization of glycemic control
      with insulin therapy in NIDDM patients.
AB  - OBJECTIVE: To evaluate the effect of glycemic control improvement with insulin
      therapy on lipoprotein(a) [Lp(a)] levels in patients with NIDDM. RESEARCH DESIGN
      AND METHODS: We performed a longitudinal study in a tertiary referral center to
      compare lipid and Lp(a) levels before and after 3 months of insulin therapy in 60
      poorly controlled NIDDM patients (32 men, 28 women). Patients previously treated
      with oral hypoglycemic agents (n = 50) received one to two insulin doses, and
      those previously treated with insulin (n = 10) received multiple insulin doses.
      Lp(a) levels were measured by the Terumo method. Differences between the two
      periods were assessed by the paired t test and Wilcoxon's test. RESULTS: After 3
      months of insulin therapy, HbA1c decreased from 9.6 +/- 1.9 to 6.0 +/- 1.4% (P <
      0.0005) in all patients and from 9.1 +/- 2.1 to 6.1 +/- 2.9% (P < 0.05) in
      patients under multiple insulin doses, being < or = 6.0% in 59% of patients.
      Total triglyceride and VLDL cholesterol levels decreased (P < 0.01) and HDL
      cholesterol increased significantly (P < 0.0005). However, no changes in Lp(a)
      levels were observed in all patients (25.3 +/- 25.0 vs 25.7 +/- 27.2% mg/dl) and
      in patients with baseline Lp(a) levels above (63.5 +/- 15.5 vs. 65.1 +/- 23.1
      mg/dl) or below 30 mg/dl (11.5 +/- 7.5 vs. 11.5 +/- 7.3 mg/dl). In addition,
      patients reaching HbA1c levels < or = 6.0% or > 6.0% presented similar Lp(a)
      levels (26.0 +/- 29.1 vs 25.3 +/- 25.0 mg/dl). Moreover, no correlations were
      observed between changes in Lp(a) levels and in the glycemic control parameters.
      CONCLUSIONS: This study shows that the improvement of glycemic control by insulin
      therapy does not influence plasma Lp(a) levels, measured by the Terumo method, in
      NIDDM patients, independently of baseline values and the degree of glycemic
      control reached.

PMID- 9283798
TI  - Adherence of mononuclear cells to endothelium in vitro is increased in patients
      with NIDDM.
AB  - OBJECTIVE: To compare the binding to cultured endothelial cells of mononuclear
      cells isolated from healthy volunteers and patients with NIDDM. RESEARCH DESIGN
      AND METHODS: Mononuclear cells were isolated from healthy volunteers (n = 11) and
      patients with NIDDM (n = 14) and incubated with ECV 304 cells, a human umbilical
      endothelial cell-derived transformed cell line. Following a period of incubation,
      the adherence of mononuclear cells to endothelial cells was determined. RESULTS:
      Adherence of mononuclear cells from patients with NIDDM was significantly greater
      (P < 0.05) than that of cells isolated from the healthy volunteers, and this
      difference persisted when adjusted for age, sex, and degree of obesity.
      Mononuclear cell binding to ECV 304 cells correlated significantly with fasting
      plasma glucose (r = 0.52, P < 0.01), insulin (r = 0.51, P < 0.01), triglyceride
      (r = 0.54, P < 0.01), and VLDL (r = 0.54, P < 0.01) and HDL cholesterol (r = 
      0.45, P < 0.05) levels, but not with either total or LDL cholesterol levels or
      blood pressure. CONCLUSIONS: Since the adherence of mononuclear cells to the
      endothelium represents the earliest step in atherogenesis, the observation that
      mononuclear cells from patients with NIDDM bind more avidly to cultured
      endothelial cells may help explain why accelerated atherosclerosis occurs in
      patients with NIDDM. The metabolic abnormality, or abnormalities, present in
      patients with NIDDM that is responsible for the enhanced adhesiveness of
      mononuclear cells requires further examination.

PMID- 9283799
TI  - Effects of glycemic control on plasma 3-deoxyglucosone levels in NIDDM patients.
AB  - OBJECTIVE: To clarify the effects of glycemic control on the level of 3
      deoxyglucosone (3-DG), a reactive dicarbonyl compound, in plasma from diabetic
      patients. RESEARCH DESIGN AND METHODS: Fasting plasma samples were collected from
      15 healthy volunteers and 27 patients with NIDDM. Samples were collected from six
      poorly controlled patients before and after improved glycemic control for at
      least 2 months. Plasma 3-DG was determined by high-performance liquid
      chromatography (HPLC) as a 2,3-diaminonaphthalene derivative. We observed the
      relationship of 3-DG levels with plasma glucose or HbA1c levels and examined
      changes in 3-DG levels after glycemic control in the six patients. RESULTS:
      Plasma 3-DG was significantly more increased in diabetic patients than in
      nondiabetic control subjects (31.8 +/- 11.3 vs. 12.8 +/- 5.2 ng/ml, means +/- SD,
      P < 0.001), but there was an approximately threefold difference in 3-DG levels
      among diabetic patients. 3-DG levels were well correlated with plasma glucose (r
      = 0.56, P < 0.005) and HbA1c levels (r = 0.74, P < 0.001) in diabetic patients.
      The improvement of hyperglycemia in six patients resulted in a significant
      decrease in 3-DG (35.2 +/- 13.2 vs. 21.3 +/- 3.4 ng/ml, P < 0.05). CONCLUSIONS:
      The results indicate that the plasma glucose level is a predominant determinant
      of the plasma 3-DG level in diabetic patients and good glycemic control would be
      important to reduce this reactive metabolite.

PMID- 9283800
TI  - Longitudinal study of carbohydrate metabolism in healthy obese pregnant women.
AB  - OBJECTIVE: To longitudinally characterize changes in insulin sensitivity in obese
      women during and after pregnancy. RESEARCH DESIGN AND METHODS: Six glucose
      tolerant obese women underwent a 4-h euglycemic-hyperinsulinemic (500-600 pmol/l)
      clamping during the second (22.5 +/- 2 weeks [mean +/- SD]) and third trimester
      (36.8 +/- 0.9) of pregnancy and again 15.6 +/- 1.4 weeks after delivery. Rates of
      total body glucose turnover (with [6.6-2H2]glucose) and oxidation (with indirect
      calorimetry) were measured. RESULTS: There were no significant changes with
      respect to the action of insulin on rates of glucose disappearance (GRd),
      carbohydrate oxidation, or endogenous glucose production (EGP), comparing the
      second trimester of pregnancy with the nonpregnant (postpartum) state. The third
      trimester, however, was characterized 1) by reductions in insulin-stimulated GRd
      (-28%, P < 0.05, compared with the second trimester and -40%, P < 0.05, compared
      with postpartum); 2) by even larger reductions in insulin-stimulated carbohydrate
      oxidation (-46%, P < 0.05, compared with the second trimester and -54%, P < 0.02,
      compared with postpartum); and 3) by reduction of insulin suppression of EGP (
      39% compared with -79% at the second trimester and -77% postpartum, P < 0.01).
      CONCLUSIONS: Glucose-tolerant obese women developed peripheral was well as
      hepatic insulin resistance during the third trimester of pregnancy. These
      alterations were reversed after delivery and appeared to be adaptive mechanisms
      to cope with the increased demand for glucose of the growing fetus.

PMID- 9283801
TI  - Evidence that plasma leptin and insulin levels are associated with body adiposity
      via different mechanisms.
AB  - OBJECTIVE: Like insulin, the adipocyte hormone, leptin, circulates at levels
      proportionate to body adiposity. Because insulin may regulate leptin secretion,
      we sought to determine if plasma leptin levels are coupled to body adiposity via
      changes in circulating insulin levels or insulin sensitivity and whether leptin
      secretion from adipocytes is impaired in subjects with NIDDM. RESEARCH DESIGN AND
      METHODS: We used multiple linear regression to analyze relationships between BMI
      (a measure of body adiposity) and fasting plasma levels of leptin and insulin in
      98 nondiabetic human subjects (68 men/30 women) and 38 subjects with NIDDM (27
      men/11 women). The insulin sensitivity index (Si) was also determined in a subset
      of nondiabetic subjects (n = 38). RESULTS: Fasting plasma leptin concentrations
      were correlated to both BMI (r = 0.66, P = 0.0001) and fasting plasma insulin
      levels (r = 0.65, P = 0.0001) in nondiabetic men and women (r = 0.58, P = 0.0009
      for BMI; r = 0.47, P = 0.01 for insulin). While the plasma leptin level was also
      inversely related to Si (r = -0.35; P = 0.03), this association was dependent on
      BMI, whereas the association between insulin and Si was not. Conversely, the
      relationship between plasma leptin and BMI was independent of Si, whereas that
      between insulin and BMI was dependent on Si. The relationship between plasma
      leptin levels and BMI did not differ significantly among NIDDM subjects from that
      observed in nondiabetic subjects. CONCLUSIONS: We conclude that 1) body
      adiposity, sex, and the fasting insulin level are independently associated with
      plasma leptin level; 2) because NIDDM does not influence leptin levels, obesity
      associated with NIDDM is unlikely to result from impaired leptin secretion; and
      3) insulin sensitivity contributes to the association between body adiposity and
      plasma levels of insulin, but not leptin. The mechanisms underlying the
      association between body adiposity and circulating levels of these two hormones,
      therefore, appear to be different.

PMID- 9283803
TI  - Topics in type 2 diabetes.

PMID- 9283802
TI  - The efficacy of self-monitoring of blood glucose in NIDDM subjects. A criteria
      based literature review.
AB  - OBJECTIVE: To determine the efficacy of self-monitoring of blood glucose (SMBG)
      in NIDDM patients from studies published during the years 1976-1996. RESEARCH
      DESIGN AND METHODS: A systematic literature search was conducted. The selected
      studies were assessed for their methodological quality and reviewed on the
      reported efficacy and on the following topics: characteristics of the study
      population, follow-up duration, nature of the efficacy measures, use of a therapy
      decision scheme, nature of the intervention, nature of the SMBG device, patient
      instruction, type of SMBG regime, assessment of the frequency of self
      measurement, and whether feedback was given on the measured glucose levels.
      Studies with positive conclusions on the efficacy of SMBG were compared with
      studies with negative conclusions on the basis of the these characteristics to
      determine which factors could have contributed to the results. RESULTS: Of the 11
      studies identified, only 4 met all quality criteria. Six of the studies were
      randomized controlled trials, of which only one showed positive conclusions
      regarding the efficacy of SMBG. Although the studies differed on most topics, no
      factor could be identified as responsible for the results of the studies.
      CONCLUSIONS: The efficacy of SMBG in NIDDM patients is still questionable and
      should be tested in a rigorous high-quality randomized controlled trial, for
      which some recommendations are given.

PMID- 9283804
TI  - Insulin responses to oral glucose during 4-year treatment with nifedipine retard
      in hypertensive patients with and without NIDDM.

PMID- 9283805
TI  - Retinopathy and type 2 diabetes.

PMID- 9283806
TI  - Involvement of the musculotendinous apparatus in flexion contractures of limited
      joint mobility of the diabetic hand.

PMID- 9283807
TI  - Absolute benefit from cholesterol lowering in diabetic patients with coronary
      heart disease.

PMID- 9283809
TI  - Outcomes in diabetic patients.

PMID- 9283808
TI  - Higher serum sialic acid in women than in men with NIDDM: possible relevance to
      increased cardiovascular risk in NIDDM women.

PMID- 9283810
TI  - Modulation of NCAM polysialylation is associated with morphofunctional
      modifications in the hypothalamo-neurohypophysial system during lactation.
AB  - Post-transcriptional modification of the neural cell adhesion molecule (NCAM) by
      polysialic acid significantly decreases NCAM adhesiveness and more generally
      modifies cell-cell interactions. Polysialic acid-NCAM (PSA-NCAM) is mainly
      expressed in the developing nervous system. In the adult, its expression is
      restricted to regions that retain morphological plasticity, such as the
      hypothalamo-neurohypophysial system during lactation in rats. Since cell-cell
      interactions and synaptic contacts in the hypothalamo-neurohypophysial system are
      greatly increased during lactation, we examined whether PSA-NCAM expression is
      modified during this period. Immunohistochemistry and immunoblotting showed that,
      compared with virgin rats, PSA-NCAM dramatically decreased during lactation in
      both the supraoptic nuclei and the neurohypophysis, and returned to its initial
      level only after weaning. This decrease was progressive and became significant
      only at the end of the first week of lactation. By contrast, modifications in the
      level of NCAM protein or changes in the splicing pattern of NCAM mRNAs could not
      be detected. The decline in polysialic acid on the NCAM molecule could strengthen
      membrane appositions, thereby stabilizing the newly established synapses and
      neurohaemal contacts in the hypothalamo-neurohypophysial system that accompany
      the increased neuronal activity that occurs during lactation. We also studied the
      regulation of the phosphorylated microtubule-associated protein-1B (MAP1B-P),
      whose distribution pattern largely overlaps with that of PSA-NCAM in the adult
      brain. Expression of MAP1B-P was greatly increased during lactation in the
      hypothalamic axons projecting into the neurohypophysis. Thus, the expression
      patterns of both PSA-NCAM and MAP1B-P may reflect the permanent structural
      plasticity characterizing the hypothalamo-neurohypophysial system in the adult.

PMID- 9283811
TI  - Hypothyroidism alters the expression of prostaglandin D2 synthase/beta trace in
      specific areas of the developing rat brain.
AB  - Lipocalin-type prostaglandin D2 synthase is the enzyme responsible for the
      synthesis of prostaglandin D2, a major prostaglandin in the central nervous
      system. We analysed the effects of thyroid hormone deprivation on prostaglandin
      D2 synthase gene expression in the developing rat brain. By in situ
      hybridization, the strongest prostaglandin D2 synthase mRNA signal was detected
      in the leptomeninges and choroid plexus. The signal was greatly reduced in the
      cerebellar interlaminar meninges of hypothyroid rats aged 15 and 25 days.
      Immunohistochemical studies defined changes in the location of the prostaglandin
      D2 synthase protein. In control but not in hypothyroid animals, Cajal-Retzius
      neurons of cortical layer I, and pyramidal cortical plate neurons were intensely
      stained on postnatal day 5. Conversely, prostaglandin D2 synthase protein levels
      were higher in neurons of the CA1 and CA3 regions and the dentate gyrus of the
      hippocampus of hypothyroid animals on postnatal days 5, 15 and 25, and also in
      subplate neurons on postnatal days 15 and 25. In agreement with the in situ
      hybridization and northern blotting data, the major difference was found in the
      cerebellar interlaminar meninges of hypothyroid animals, where the protein was
      clearly down-regulated on postnatal days 15 and 25. These results show that
      hypothyroidism causes both age- and region-specific alterations in the expression
      and location of the prostaglandin D2 synthase during postnatal brain development,
      probably reflecting a cell-specific regulatory effect of thyroid hormone on the
      prostaglandin D2 synthase.

PMID- 9283812
TI  - Overexpression of nerve growth factor in skin increases sensory neuron size and
      modulates Trk receptor expression.
AB  - Sensory neuron development and differentiation is dependent on a family of growth
      factors known as neurotrophins. Neurotrophins modulate neuron development via trk
      tyrosine kinase receptor proteins trkA, trkB and trkC. To determine how elevated
      levels of a target-derived neurotrophin might affect neuronal differentiation, we
      analysed trk expression in the trigeminal ganglion of transgenic mice that
      overexpressed nerve growth factor (NGF) in the skin. Increased levels of NGF
      caused a five-fold increase in neurons expressing trkA mRNA and a two-fold
      increase in neurons expressing trkC. In control mice, cell size distributions of
      neuronal subpopulations expressing each trk mRNA showed the three subpopulations
      distributed over a narrow, overlapping range. In contrast, cell size distribution
      in NGF-transgenic mice was significantly divergent due in large part to
      hypertrophy of trkA neurons and, to a lesser extent, trkC neurons. In addition,
      we examined neurons that bound the isolectin B4 from Bandeiraea simplicifolia (BS
      IB4) because most of these neurons do not express any trk receptor in the adult.
      There was a significant increase in the size of BS-IB4-positive neurons in
      transgenic mice; however, there was no increase in their number. These studies
      indicate that an increased level of target-derived NGF affects the development of
      sensory neurons that in the adult express trkA or trkC, as well as neurons that
      do not express trk receptors.

PMID- 9283814
TI  - Learning-induced changes in rat piriform cortex activity mapped using multisite
      recording with voltage sensitive dye.
AB  - The piriform cortex (PCx) has a potential role in storage and recall of olfactory
      information. This study is a first extensive investigation of the spatiotemporal
      distribution of activity in the PCx induced by learned sensory inputs following
      conditioning. In a conditioned group, rats chronically implanted with four
      electrodes in the olfactory bulb were trained to associate the electrical
      stimulation of a given bulbar electrode with a positive reinforcement, while
      stimulation of a different electrode predicted a negative reinforcement. In a
      familiarized group, rats received the same protocol of daily electrical
      stimulation with no associated reinforcement. At the end of the conditioning or
      familiarization episode, activity evoked in the PCx was optically mapped using a
      144 photodiode array. In the anaesthetized rats, PCx maps were recorded in
      response to stimulation of each of the four bulbar electrodes using either high
      (0.5-1 mA) or low (0.1 mA) test current intensities. Low intensity stimulation
      revealed that conditioning selectively enhanced the probability of occurrence of
      a signal composed of a single late (56-73 ms) component which occurred almost
      simultaneously on a large PCx area. In the conditioned group, high intensity
      stimulation through either of the four electrodes revealed a potentiation of the
      early (17-30 ms) disynaptic component of the PCx response in the most posterior
      part of the PCx as well as a homogeneous increase of the late (39-52 ms)
      component spread over the PCx areas. These data suggest that learning induces
      synaptic changes at different nodes of the PCx circuitry.

PMID- 9283813
TI  - Elimination of motor nerve terminals in neonatal mice expressing a gene for slow
      wallerian degeneration (C57Bl/Wlds).
AB  - Degeneration of motor terminals after nerve section occurs much more slowly than
      normal in young adult mice of the C57Bl/Wlds strain. This observation prompted us
      to re-examine the possible role of degeneration and intrinsic axon withdrawal
      during neonatal synapse elimination. Polyneuronal innervation was assayed by two
      methods: intracellular recording of end-plate potentials in cut-muscle fibre
      preparations of isolated hemidiaphragm and soleus muscles; and in silver-stained
      preparations of triangularis sterni and transversus abdominis muscle fibres. No
      differences in the rate of synapse elimination were detected in unoperated Wlds
      compared with CBA, C3H/HE and BALB/c mice. At 3 days of age, > 80% of fibres were
      polyneuronally innervated. By 7 days this declined to approximately 20% of
      hemidiaphragm, 50% of triangularis sterni and 60% of soleus fibres. Nearly all
      fibres were mononeuronally innervated by 15 days. The mean number of terminals
      per triangularis sterni muscle fibre 7 days after birth was 1.55 +/- 0.07 in Wlds
      and 1.56 +/- 0.09 in wild-type mice. Three to 4 days after sciatic nerve section,
      near-normal numbers of motor units were evident in isometric tension recordings
      of the soleus muscle, and intracellular recordings revealed many polyneuronally
      innervated fibres. Mononeuronally and polyneuronally innervated fibres were also
      observed in silver-stained preparations of soleus and transversus abdominis
      muscles made 3-4 days after sciatic or intercostal nerve section. We conclude (i)
      that the Wlds gene has no direct impact on the normal rate of postnatal synapse
      elimination, (ii) that Wallerian degeneration and synapse elimination must occur
      by distinct and different mechanisms, and (iii) that muscle fibres are able to
      sustain polyneuronal synaptic inputs even after motor axons have become
      disconnected from their cell bodies.

PMID- 9283815
TI  - Short- and long-term plasticity of the hippocampus to nucleus accumbens and
      prefrontal cortex pathways in the rat, in vivo.
AB  - The pathways from the hippocampal formation to the nucleus accumbens and the
      prefrontal cortex are likely to play a role in several aspects of learning and
      memory. In the present study we addressed the question of how plastic changes in
      these structures may occur simultaneously. This question can be studied in an
      appropriate way in the hippocampal/fornix-fimbria to prefrontal cortex/nucleus
      accumbens system, since electrical stimulation of the fornix-fimbria fibre bundle
      evokes characteristic field potentials in the two target areas simultaneously.
      First, we examined the termination field in the nucleus accumbens (medial shell
      and core region with an extension into the ventro-medial caudate-putamen) and the
      prefrontal cortex (deeper layers of the ventral prelimbic and ventral infralimbic
      areas) by recording single unit activity evoked by stimulation of fornix-fimbria
      fibres in halothane anaesthetized rats. Second, we studied short-term plasticity,
      namely paired pulse facilitation, in these two areas upon stimulation of the
      fornix-fimbria fibres. In the nucleus accumbens, paired pulse facilitation was
      encountered for double pulse intervals between 25 and 500 ms, peaking around 100
      ms. In the medial prefrontal cortex it was confined to intervals between 25 and
      200 ms, with a peak around 75 ms. Third, we investigated whether LTP could be
      elicited simultaneously in the two target structures by a single tetanic
      stimulation (50 Hz, 2 s) of the fornix-fimbria fibres. LTP that was sustained for
      more than 90 min in the medial prefrontal cortex, reached levels of 130% of
      control values. In the nucleus accumbens, however, only a transient form of
      potentiation was found which lasted no more than 60 min. These data show that
      synaptic weights can be changed in several target structures of the hippocampal
      formation, simultaneously, in a distributed way.

PMID- 9283816
TI  - Postnatal changes in electrophysiological properties of rat nucleus tractus
      solitarii neurons.
AB  - Whole-cell recordings in brainstem slices revealed postnatal changes in passive
      and firing properties in the rat caudal nucleus tractus solitarii (cNTS) neurons.
      Membrane potential, threshold for Na+ spike and degree of sag were unchanged
      during development. In the adult, the rheobase was twice that found at birth. The
      input resistance decreased over the period studied, while time constants declined
      markedly after the third postnatal week. At all postnatal ages, Na(+)-dependent
      action potentials (APs) were elicited in response to depolarization.
      Nevertheless, AP duration gradually decreased by 40% over the developmental
      period studied. Spike amplitude was smaller at birth than at any other ages and
      reached a peak two weeks after birth. At all ages, Na(+)-dependent APs were
      blocked by application of tetrodotoxin. Full APs were replaced by an initial slow
      oscillation in young cells and by oscillations in older cells. The TTX-resistant
      oscillations were altered by cobalt (2 mM) and cadmium (100 microM). The spike
      afterhyperpolarization (AHP) was not altered during development, but was observed
      in less neurons in adult cells when measured at a holding potential of -60 mV.
      Neurons were subdivided into one of three classes based on their responses to a
      hyperpolarizing prepulse: 1) post-inhibitory rebound (PIR) cells, 2) delayed
      excitation (DE) cells and 3) NON cells expressing neither PIR nor DE. The
      relative proportions of different cell types varied with age. The mean maximum
      duration of DE increased three times. Voltage-clamp experiments revealed that the
      DE was due to the activation of an A-current. In addition, a three-fold increase
      in its inactivation rate was observed postnatally. The physiological significance
      of these results is discussed.

PMID- 9283817
TI  - Interneuron-specific Ca2+ responses linked to metabotropic and ionotropic
      glutamate receptors in rat hippocampal slices.
AB  - Glutamate-mediated regulation of intracellular Ca2+ levels was examined in
      different populations of CA1 interneurons, using confocal microscopy and the Ca2+
      indicator fluo 3-AM in rat hippocampal slices. Interneurons in basal [stratum
      oriens/alveus (OA)] and apical [strata radiatum and lacunosum-moleculare (R/LM)]
      dendritic layers responded heterogeneously to glutamate. In control medium, OA
      interneurons responded mostly with oscillatory Ca2+ responses, which consisted of
      a large Ca2+ transient and successive smaller elevations. R/LM interneurons
      responded mostly with biphasic responses, characterized by an initial large
      transient and a secondary prolonged elevation. Other interneurons in both R/LM
      and OA responded with transient elevations in Ca2+ levels. Ionotropic glutamate
      receptor antagonists (+/-)2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitro
      quinoxaline-2,3-dione reduced peak Ca2+ responses in OA and R/LM cells, and
      blocked biphasic responses in R/LM interneurons. The metabotropic glutamate
      receptor antagonist (RS)-alpha-methyl-4-carboxyphenylglycine reduced peak Ca2+
      responses only in OA interneurons, and prevented oscillatory responses. In low
      Ca2+ medium, peak responses were reduced in R/LM but not in OA interneurons, and
      oscillatory responses were absent. Combination of ionotropic and metabotropic
      receptor antagonists blocked all glutamate-evoked Ca2+ responses. Activation of
      different types of glutamate receptors may thus produce heterogeneous Ca2+
      signals in subpopulations of CA1 interneurons. Ionotropic receptors may generate
      biphasic responses in interneurons in apical dendritic layers, whereas combined
      activation of metabotropic and ionotropic receptors may trigger oscillatory
      responses in interneurons of basal dendritic layers. These heterogeneous Ca2+
      responses indicate that glutamate-mediated Ca2+ processes and second messenger
      systems differ in subpopulations of hippocampal interneurons and suggest possible
      postsynaptic functional specialization of interneurons.

PMID- 9283818
TI  - Sensory-induced plasticity of motor pattern selection in the lobster
      stomatogastric nervous system.
AB  - In a previous study, a bilateral sensory input pathway to the crustacean
      stomatogastric nervous system was reported to induce the functional switching of
      an identified motor neuron (VD) from one rhythm generating neural network (the
      pyloric circuit) to another (the cardiac sac network). In the present in vitro
      study on the spiny lobster, Palinurus vulgaris, we have shown that under certain
      conditions, repetitive trains of phasic stimulation (1 s, 40 Hz) of one of these
      sensory nerves elicits either an increase or a decrease in efficacy of the VD
      switching response. In preparations showing no previous sign either of increase
      or decrease in VD switching, either response can be induced by prior conditioning
      stimulation. The increasing effect can be induced by unpaired conditioning
      stimulation of the contralateral sensory nerve. Conversely, the decrease in
      switching efficacy is obtained by pairing stimulation of the sensory-motor
      pathway with that applied to its contralateral partner. Both the experimentally
      induced increase and decrease in VD switching are long-lasting, remaining
      observable for at least 20 min and in some cases up to 3 h after the original
      conditioning procedure. Our results suggest that this system provides a suitable
      'simple' model for the analysis of experience-related plasticity of the switching
      of a neuron from one network to another.

PMID- 9283819
TI  - Differential developmental expression of the two rat brain glutamate transporter
      proteins GLAST and GLT.
AB  - The extracellular concentration of the excitatory neurotransmitter glutamate is
      kept low by the action of glutamate transporters in the plasma membranes of both
      neurons and glial cells. These transporters may play important roles, not only in
      the adult brain, but also in the developing brain, as glutamate is thought to
      modulate the formation and elimination of synapses as well as neuronal migration,
      proliferation and apoptosis. Here we demonstrate the developmental changes in the
      expression of two glutamate transporters, GLAST and GLT, by quantitative
      immunoblotting and by light and electron microscopic immunocytochemistry. At
      birth, GLT is not detectable, but GLAST is present at significant concentrations
      both in the forebrain and in the cerebellum. GLT is first detected in the
      forebrain and cerebellum in the second and third week, respectively. Both
      transporters reach adult levels by postnatal week 5. The development of the total
      glutamate uptake activity in the forebrain, as determined by solubilization and
      reconstitution of the transporters in liposomes, parallels that of GLT, in
      agreement with the observation that GLT is the predominant transporter in the
      adult brain. The regional distributions of both GLAST and GLT in the tissue are
      similar in young and adult rats. Only GLAST is detectable in the external
      germinal layer of the cerebellar cortex. Electron microscopical investigation
      demonstrated GLAST and GLT exclusively in glial cells in young as well as in
      adult animals.

PMID- 9283820
TI  - Relations between long-term synaptic modifications and paired-pulse interactions
      in the rat neocortex.
AB  - The phenomenon of paired-pulse facilitation (PPF) was exploited to investigate
      the role of presynaptic mechanisms in the induction and maintenance of long-term
      synaptic plasticity in the neocortex. Long-term potentiation (LTP) and depression
      (LTD) were induced without afferent activation by applying tetani of
      intracellular pulses. Our results show that synaptic modifications closely
      resembling LTP and LTD can be induced by postsynaptic activation alone. The
      polarity of these synaptic modifications depends on initial properties of the
      input, as indicated by a correlation between initial PPF ratio and post-tetanic
      amplitude changes: inputs exhibiting strong PPF, which might be associated with
      low release probability tend to be potentiated, while inputs with small PPF are
      more likely to show depression. Maintenance of both LTP and LTD involve
      presynaptic mechanisms, as indicated by changes in PPF ratios and in failure rate
      after LTP or LTD induction. Presynaptic mechanisms could include changes in
      release probability and/or in the number of active release sites. Because
      induction was postsynaptic, this supports the notion of a retrograde signal. The
      relative contribution of pre- and postsynaptic mechanisms in the maintenance of
      long-term synaptic modifications depends on the initial state of the synaptic
      input and on LTP magnitude. PPF changes were especially pronounced in inputs
      which had initially high PPF and underwent strong potentiation. Since LTP and LTD
      are associated with changes of PPF ratios these synaptic modifications do not
      only alter the gain but also the temporal properties of synaptic transmission.
      Because of the LTP associated reduction of PPF, potentiated inputs profit less
      from temporal summation, favouring transmission of synchronized, low frequency
      activity.

PMID- 9283821
TI  - Male faces and odours evoke differential patterns of neurochemical release in the
      mediobasal hypothalamus of the ewe during oestrus: an insight into sexual
      motivation?
AB  - During behavioural oestrus female sheep, like females of many species, become
      both attracted to and sexually receptive towards males, whereas at other times
      they will avoid them. The mediobasal hypothalamus is the main site for the
      feedback action of sex steroids to induce sexual behaviour in the sheep and in
      previous studies we have shown that noradrenaline and serotonin are released in
      this region during sexual interactions with males. The current study investigated
      whether such changes are specific to interactions with males and if visual or
      olfactory cues or somatosensory stimulation during mating are critical. In vivo
      microdialysis sampling was carried out in the mediobasal hypothalamus of
      ovariectomized ewes submitted to artificial oestrous cycles. Release of
      monoamines and amino acid transmitters was first measured in animals during and
      after oestrus when they were exposed to interactions with either males or females
      or presentation of food. Noradrenaline concentrations only increased
      significantly when the females were in oestrus and interacted with males
      irrespective of whether intromissions were permitted. Females were then exposed
      to visual (faces) or odour (a home pen) cues from males or to the males
      themselves. Slide images of male faces increased concentrations of amines,
      glutamate and GABA during early oestrus, when females spent most time looking at
      them. During late oestrus noradrenaline, glutamate and GABA concentrations also
      increased in response to the male faces but no transmitter changes were seen
      during the luteal phase or at any time where the females were exposed to female
      faces, or inverted male faces. Exposure to male odour produced a lower increase
      in noradrenaline concentrations when females were in early oestrus but marked
      increases 20 and 30 min after exposure to male odours in late oestrus. No other
      transmitters were affected. Exposure to a male and mating with him when females
      were in early or late oestrus produced increased noradrenaline concentrations
      similar to those seen with face stimuli alone although other neurotransmitters
      were unaffected. These results show that noradrenaline, and to a lesser extent
      dopamine, serotonin, glutamate and GABA release in the mediobasal hypothalamus,
      can be modulated specifically in the oestrous female by sensory information
      coming from the male during oestrus. The differential effects of male cues during
      early and late oestrus suggest their involvement in (i) proceptive or
      anticipatory sexual responses shown by the female to male cues, and (ii)
      receptive sexual responses, and suggest that the mediobasal hypothalamus plays a
      key role in the integration of hormonal action on sexual motivation and
      processing of sensory information during oestrus.

PMID- 9283822
TI  - Glutamatergic modulation of cortical acetylcholine release in the rat: a combined
      in vivo microdialysis, retrograde tracing and immunohistochemical study.
AB  - The microdialysis technique with one or two probes was used to investigate the
      modulation of cortically projecting cholinergic neurons by glutamatergic input in
      the rat in vivo. Male albino Wistar rats (250-300 g) were used. Under chloral
      hydrate anaesthesia microdialysis membranes were positioned in the parietal
      cortex, nucleus basalis magnocellularis (NBM) or medial septum. Acetylcholine was
      assayed using high-performance liquid chromatography (HPLC) with electrochemical
      detection while GABA was detected using HPLC with fluorimetric detection after
      derivatization of the amino acid with o-phthalaldehyde. Septo-cortical neurons
      were retrogradely labelled with fluoro-gold. Double labelling with choline
      acetyltransferase (ChAT) immunoreactivity was performed to identify these
      neurons. Our main findings were that: (i) i.c.v. administration of the NMDA
      antagonist 3-((R)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, 1-5
      nmol) increased cortical acetylcholine outflow; (ii) local administration of CPP
      (100 microM) to the cortex had no effect on cortical acetylcholine outflow; (iii)
      local administration of CPP (100 microM) to the NBM decreased cortical
      acetylcholine outflow; (iv) local administration of CPP (100-200 microM) to the
      septum increased cortical GABA and acetylcholine outflow; (v) administration of
      muscimol to the septum prevented the effect of CPP on cortical acetylcholine
      outflow; (vi) retrograde tracing with fluoro-gold labelled cell bodies in the
      medial septum; (vii) septal fluoro-gold-positive neurons were not ChAT
      immunoreactive. Our in vivo neurochemical results, in combination with retrograde
      tracing and immunohistochemistry, indicate that the cortically projecting
      cholinergic system is indirectly regulated by a glutamatergic input via a
      polysynaptic GABAergic circuitry located in the septum.

PMID- 9283823
TI  - Epidermal growth factor is a motility factor for microglial cells in vitro:
      evidence for EGF receptor expression.
AB  - Epidermal growth factor (EGF) and its receptor are present in the central nervous
      system and modulate a variety of neural functions. Here we show that microglial
      cells, the brain-intrinsic macrophages, express the receptor for EGF and migrate
      in response to EGF. Transcripts encoding the EGF receptor could be detected in
      purified microglial cultures obtained from newborn mouse cortex. More
      specifically, cDNA fragments derived from EGF receptor mRNA could be amplified
      from 21% of electrophysiologically characterized microglial cells by the use of a
      single-cell reverse transcription-polymerase chain reaction method. Expression of
      the protein was confirmed on rat microglia by flow cytometry. EGF dose
      dependently stimulated chemotactic migration, as revealed with a microchemotaxis
      assay. The dose-response curve peaked-at 10 ng/ml EGF, reaching a 3-fold increase
      in migration over the unstimulated control; migration was about half of that
      induced by complement 5a (10 nM), a previously described microglial
      chemoattractant. Chequerboard analysis showed that EGF-induced motility was
      composed of both chemotaxis and chemokinesis. In contrast to its pronounced
      effect on cell motility, EGF (0.01-10 ng/ml) was not a mitotic signal for
      microglia, as shown by lack of bromodeoxyuridine incorporation. Acute and chronic
      pathological processes within the brain stimulate the synthesis and release of
      immunoregulators and growth factors (including EGF) that play a major role in the
      brain's response to injury. EGF may serve as a paracrine factor to direct
      microglial cells to the lesion site. Moreover, since EGF is secreted by activated
      microglia themselves in vivo, it may act as an autocrine modulator of microglial
      cell function.

PMID- 9283824
TI  - Bone morphogenetic proteins: neurotrophic roles for midbrain dopaminergic neurons
      and implications of astroglial cells.
AB  - Bone morphogenetic proteins (BMPs) are members of the transforming growth factor
      beta (TGF-beta) superfamily that have been implicated in tissue growth and
      remodelling. Recent evidence suggests that several BMPs are expressed in the
      developing and adult brain. Specifically, we show that BMP 2 and BMP 6 are
      expressed in the developing midbrain floor of the rat. We studied potential
      neurotrophic effects of BMPs on the in vitro survival, transmitter uptake and
      protection against MPP+ toxicity of mesencephalic dopaminergic neurons cultured
      from the embryonic midbrain floor at embryonic day (E) 14. At 10 ng/ml and under
      serum-free conditions, most BMPs promoted the survival of dopaminergic neurons
      visualized by tyrosine hydroxylase immunocytochemistry during an 8-day culture
      period, but to varying extents (relative potencies: BMP 6 = 12 > 2, 4, 7). BMPs 6
      and 12 were as effective as fibroblast growth factor-2 (FGF-2) and glial cell
      line-derived neurotrophic factor, promoting survival 1.7-fold compared with
      controls. BMPs 9 and 11 were not effective. Dose-response curves revealed an EC50
      for BMPs 2, 6 and 12 of 2 ng/ml. BMPs 2, 4, 6, 7, 9 and 12 also promoted DNA
      synthesis and astroglial cell differentiation, visualized by 5-bromodeoxyuridine
      (BrdU) incorporation and glial fibrillary acidic protein (GFAP)
      immunocytochemistry respectively. Suppression of cell proliferation and
      subsequent maturation of GFAP-positive cells by 5-fluorodeoxyuridine or
      aminoadipic acid abolished the neuron survival-promoting effect of BMP 2. This
      suggests that BMPs, like other non-TGF-beta factors affecting dopaminergic neuron
      survival, act indirectly, probably by stimulating the synthesis and/or release of
      glial-derived trophic factors. BMP 6 and BMP 7 also increased the uptake of
      [3H]dopamine without affecting the uptake of [3H]5-hydroxytryptamine and
      [3H]GABA, underscoring the specificity of the trophic effect. We conclude that
      several BMPs share a neurotrophic capacity for dopaminergic midbrain neurons with
      other members of the TGF-beta superfamily, but act indirectly, possibly through
      glial cells.

PMID- 9283825
TI  - Electrophysiological evidence for multiple glycinergic inputs to neonatal rat
      sympathetic preganglionic neurons in vitro.
AB  - The time pattern of glycinergic inhibitory postsynaptic currents (IPSCs) in
      sympathetic preganglionic neurons was studied in thin transverse spinal cord
      slices of neonatal (1-10 days postnatal) rats by means of the patchclamp
      technique. Three time patterns could be distinguished: (i) large events [mostly >
      400 pA (30-36 degrees C)] occurring at regular intervals, (ii) small events
      occurring at irregular intervals, and (iii) small events occurring in transient
      (1.5-10 s), high-frequency (> 15 Hz) bursts of synaptic activity. The large
      regular events had uniform kinetics which was consistent with the idea of a
      proximal site of origin for all of these events. They were reversibly inhibited
      in amplitude and frequency by extracellular application of a high concentration
      of acetylcholine (200 microM) or the specific nicotinic acetylcholine receptor
      agonist dimethylphenylpiperazinium iodide (DMPP; 1 mM), but unaffected by
      glutamate (100 microM). IPSCs occurring in bursts had slower and less uniform
      kinetics, suggesting a more diverse site of origin. The frequency of events
      decreased during a burst. Similar bursts could be induced by extracellular
      application of glutamate receptor agonists. These results indicate that
      sympathetic pregnanglionic neurons in a thin, transverse spinal cord slice
      receive at least two different glycinergic inputs.

PMID- 9283826
TI  - Involvement of activation of dopaminergic neuronal system in learning and memory
      deficits associated with experimental mild traumatic brain injury.
AB  - Much evidence has indicated that a disturbance in dopamine neurotransmission
      following mild to moderate traumatic brain injury is involved in the development
      of post traumatic memory deficits. In the present study we examined the effects
      of a dopamine receptor agonist and some antagonists on latent learning and memory
      deficits associated with a concussive traumatic brain injury in mice.
      Anaesthetized animals were subjected to mild traumatic brain injury by dropping a
      weight onto the head, and a single-dose injection of apomorphine (0.3-3.0 mg/kg)
      or haloperidol (0.3-3.0 mg/kg) was made i.p. 15 min after the trauma. One week
      later, a water-finding task consisting of an acquisition trial, a retention test
      and a retest was employed to assess learning and memory functions. Mice that had
      received a traumatic brain injury were impaired in task performance, with
      prolonged latencies for finding and drinking in the retention test and retest.
      Administration of haloperidol but not of apomorphine significantly shortened the
      prolonged latency in both of the tests, indicating that antagonism of dopamine
      receptors is beneficial for the recovery of post traumatic memory deficits. In
      order to evaluate which receptor subtype plays the major role in this model, we
      examined the effects of SCH-23390 (0.03-0.3 mg/kg), a D1 receptor antagonist, and
      sulpiride (3.0-30 mg/kg), a D2 receptor antagonist, in the same experimental
      paradigm. The results showed that administration of sulpiride but not of SCH
      23390 significantly improved the deficits in task performance, indicating that D2
      receptors are the major site of action. However, combined treatment with SCH
      23390 (0.03-0.3 mg/kg) and sulpiride (3.0 mg/kg) at doses that had no effect when
      the antagonists were given alone exerted a significant additive effect in
      improving these deficits, indicating that interaction between D1 and D2 receptors
      is involved in these processes. The present results suggest that a dopaminergic
      mechanism contributes to the memory dysfunction associated with traumatic brain
      injury.

PMID- 9283828
TI  - A thalamic contribution to arousal-induced, non-photic entrainment of the
      circadian clock of the Syrian hamster.
AB  - It is well established that the circadian clock of the suprachiasmatic nuclei
      (SCN) is entrained by light. More recently, the potent effects of arousing, non
      photic cues on the clock have been recognized. The neural mediators of non-photic
      entrainment are yet to be identified. To examine the contribution of the thalamic
      intergeniculate leaflet (IGL) and its NPY-immunopositive projection, the geniculo
      hypothalamic tract to non-photic entrainment by arousal, male Syrian hamsters
      received lesions of the IGL (IGLX) which ablated NPY-immunoreactivity in the SCN.
      Their circadian responses to both photic and non-photic cues were then tested.
      Lesions resulted in a delay in the timing of activity onset following lights out,
      but had no effect on the behavioural or cellular circadian responses to phase
      advancing light pulses presented at circadian time (CT) CT19 (where CT12
      represents the time of activity onset). Injection with a benzodiazepine
      (chlordiazepoxide, 100 mg/kg) at CT6 suppressed wheel-running, increased general
      locomotion of intact controls and induced large phase advances of the circadian
      rhythm of wheel-running. Chlordiazepoxide also inhibited wheel-running in
      lesioned animals, but there was no significant increase in general locomotion and
      the lesioned animals did not phase advance. Serial arousal by injection of saline
      at intervals of 23.5 h for 6 days entrained the circadian rhythm of wheel-running
      of intact hamsters and was associated with an increase in general locomotor
      activity. Entrainment by serial arousal was abolished by IGLX. However, the
      lesioned animals did show a clear behavioural response to every presentation of
      the non-photic cue. These results show that the IGL is a necessary component of
      the neural pathways mediating both arousal- and benzodiazepine-induced non-photic
      entrainment.

PMID- 9283827
TI  - Antidepressant drugs inhibit a glial 5-hydroxytryptamine transporter in rat
      brain.
AB  - We assessed the role of glial cells in the uptake of serotonin (5
      hydroxytryptamine, 5-HT). Primary cultures of rat and mouse cortical astrocytes
      took up and deaminated 5-HT. The antidepressants citalopram, clomipramine,
      fluoxetine, fluvoxamine, paroxetine and sertraline inhibited this process. The
      presence of the mRNAs for the 5-HT transporter and monoamine oxidase-A (MOA-A)
      was established in cultured astrocytes and in adult rat brain areas with
      (midbrain and brainstem) and without (frontal cortex) serotonergic cell bodies
      after reverse transcription-polymerase chain reaction and hybridization with
      probes complementary to the cloned neuronal 5-HT transporter and MAO-A. To
      examine in vivo the role of astrocytes in the elimination of 5-HT from the
      extracellular brain space, 5-HT was perfused through dialysis probes implanted in
      the frontal cortex of conscious rats and its concentration was measured at the
      probe outlet. Tissue 5-HT recovery was dose-dependently inhibited by the
      concurrent perfusion of citalopram, fluoxetine and paroxetine, showing that it
      essentially measured uptake through the high-affinity 5-HT transporter. Rats
      lesioned with 5,7-dihydroxytryptamine (5,7-DHT; 88% reduction of tissue 5-HT)
      displayed tissue 5-HT recovery slightly higher than sham-operated rats (55 +/- 2
      vs. 46 +/- 3%, P < 0.001), a finding perhaps attributable to the astrogliosis
      induced by 5,7-DHT denervation. Rats lesioned with 6-hydroxydopamine showed
      tissue 5-HT uptake similar to controls, suggesting negligible reuptake of 5-HT by
      catecholaminergic terminals. These results are consistent with the presence of a
      glial component of 5-HT uptake in the rodent brain, sensitive to antidepressants,
      which takes place through a 5-HT transporter very similar or identical to that
      present in neurons.

PMID- 9283829
TI  - Glycosaminoglycan supplementation promotes nerve regeneration and muscle
      reinnervation.
AB  - This study shows that treatment of rats with exogenous glycosaminoglycans
      stimulates peripheral nerve regeneration, increases the abundance of mRNAs for
      myelin proteins and promotes muscle reinnervation. After the sciatic nerve had
      been crushed the number of regenerating axons in the distal stump was markedly
      and highly significantly increased by glycosaminoglycan treatment throughout the
      experimental period. The increased number of axons was correlated with increased
      axon and fibre (axon+myelin) diameter. The abundance of mRNAs for P0 protein and
      myelin basic protein of regenerating nerves was also affected by treatment with
      glycosaminoglycans. The increase in mRNA was also observed in the contralateral
      unlesioned nerve. Such a phenomenon did not occur in saline-treated rats.
      Glycosaminoglycan treatment markedly increased the number of muscle fibres
      reinnervated and accelerated the restoration of muscle twitch tension elicited by
      nerve stimulation. The effect was particularly evident during the early stages
      (16 and 21 days after nerve crush) of muscle reinnervation.

PMID- 9283830
TI  - Development of orientation preference maps in area 18 of kitten visual cortex.
AB  - We investigated the development of orientation preference maps in the visual
      cortex of kittens by repeated optical imaging from the same animal. Orientation
      maps became detectable for the first time around postnatal day (P) 17 and
      improved continuously in strength unitl P30, the time at which their appearance
      became adultlike. During this developmental period the overall geometry of the
      maps remained unchanged, suggesting that the layout of the orientation map is
      specified prior to P17. Hence, before the visual cortex becomes susceptible to
      experience-dependent modifications its functional architecture is largely
      specified. This suggests that the initial development and layout of orientation
      preference maps are determined by intrinsic processes that are independent of
      visual experience. This conclusion is further supported by the result that
      orientation maps were well expressed at P24 in binocularly deprived kittens.
      Because the appearance of the first orientation-selective neurons and the
      subsequent development of orientation preference maps correlated well with the
      time course of the expression and refinement of clustered horizontal connections,
      we propose that these connections might contribute to the specification of
      orientation preference maps.

PMID- 9283831
TI  - Up-regulation of Bax protein in degenerating retinal ganglion cells precedes
      apoptotic cell death after optic nerve lesion in the rat.
AB  - Retrograde degeneration of retinal ganglion cells as a consequence of optic nerve
      lesion has been shown to fulfil the criteria of apoptosis. In the present study,
      we investigated the time course of ganglion cell apoptosis following intraorbital
      crushing of the optic nerve in adult rats using morphological criteria and
      applying a terminal transferase technique (TUNEL) for in situ detection of DNA
      strand breaks. In addition, we examined expression patterns of the anti-apoptotic
      proteins Bcl-2 and Bcl-X and the cell death-promoting protein Bax in retinae
      after crushing the optic nerve. Apoptotic nuclei were detected in the ganglion
      cell layer in the first 3 weeks after optic nerve crush, with a peak after 6
      days. Bcl-2 and Bcl-X proteins were expressed in ganglion cells at low levels.
      Expression of Bcl-2 decreased further during the days following crush. Bcl-X
      expression was initially increased, followed by a decline over the following
      days. In contrast, Bax protein, which was expressed in most ganglion cells at
      moderate baseline levels, was sharply increased as early as 30 min after crush,
      reached peak levels after 3 days, and remained up-regulated for at least 1 week
      thereafter. Double labelling for Bax and TUNEL in retinal sections, however, did
      not reveal colocalization of the two signals in individual retinal ganglion
      cells, consistent with the idea that increases in Bax precede apoptosis after
      optic nerve lesion. Thus, retinal ganglion cell death might be prevented by
      ablation of Bax protein in these cells, or by up-regulation of Bax-antagonists
      such as Bcl-2 or Bcl-X.

PMID- 9283832
TI  - Distinct effects of clostridial toxins on activity-dependent modulation of
      autaptic responses in cultured hippocampal neurons.
AB  - Clostridial neurotoxins proteolyse specific proteins implicated in synaptic
      vesicle exocytosis, but their actions on the release machinery in functional
      synapses is not well understood. Here we examine the effects of botulinum toxin A
      (BoNT/A) and tetanus toxin (TeTx) on autaptic transmission in cultured rat
      hippocampal neurons using whole-cell voltage clamp recordings. The proportion of
      cells responding to stimulation with an excitatory postsynaptic current (EPSC)
      and the magnitude of the remaining responses decreased gradually with increasing
      concentration of either toxin. However, the activity-dependent modulation (5 Hz
      repetitive stimulation) of EPSCs remaining after toxin inhibition differed
      markedly between the two toxins. The TeTx inhibition was associated with a
      persistent activity-dependent depression similar to that in control cells. In
      contrast, the BoNT/A inhibition was accompanied by a reversal of the modulation
      into facilitation, resembling that induced by lowering of the calcium
      concentration. These results demonstrate a difference between BoNT/A and TeTx in
      their mode of inhibition of synaptic vesicle exocytosis, which suggests that they
      exert their preferential actions at distinct steps of the release process.

PMID- 9283833
TI  - Chronic loss of glucocorticoids following adrenalectomy down-regulates the
      expression of glucocorticoid receptor mRNA in the rat forebrain.
AB  - In the negative feedback model, loss of endogenous glucocorticoids up-regulates
      the expression of glucocorticoid receptor mRNA. To elucidate further the effect
      of chronic lack of glucocorticoids on the expression of glucocorticoid receptor
      mRNA and protein, in situ hybridization and immunohistochemical methods were used
      to examine the long-term alteration of glucocorticoid receptor mRNA and its
      immunoreactivity in the forebrain of adrenalectomized rats. Constant lack of
      glucocorticoids resulted in marked decrease in the expression of glucocorticoid
      receptor mRNA and disappearance of glucocorticoid receptor immunoreactivity in
      many forebrain structures. In particular, in the suprapyramidal blade of the
      hippocampal granule cell layer and cerebral cortex, many cells showed almost no
      glucocorticoid receptor mRNA signals. These results suggest that long-term loss
      of endogenous glucocorticoids down-regulates the levels of glucocorticoid
      receptor mRNA, leading to reduction in the synthesis of glucocorticoid receptors
      in the rat forebrain. Therefore, the presence of endogenous glucocorticoids is
      vital to the continued expression of glucocorticoid receptor mRNA.

PMID- 9283834
TI  - Neurites of period-expressing PDH cells in the fly's optic lobe exhibit circadian
      oscillations in morphology.
AB  - Circadian rhythms have been shown both in the expression of the period (per) gene
      in 'lateral neurons' and in cells of the outermost neuropil, or lamina, of the
      fly's optic lobe. Some lateral neurons also exhibit PDH peptide-like
      immunoreactivity, arborizing widely throughout the optic lobe. Using confocal
      microscopy in the housefly, we analysed the size and spacing of PDH neurite
      varicosities, sites of possible peptide release exhibiting circadian rhythmicity.
      During the subjective day in constant darkness, there were fewer, larger
      varicosities than during subjective night. The endogenous rhythm was masked by
      the light exposure that occurred under a day-night cycle and continuous light
      conditions. Our findings indicate that PDH neurites convey circadian information
      out from the pacemaker, where they could regulate the circadian rhythms that have
      been described in the lamina, possibly via cyclical release of their peptide.

PMID- 9283835
TI  - Spatial view cells in the primate hippocampus.
AB  - Hippocampal function was analysed by making recordings in rhesus monkeys actively
      walking in the laboratory. In a sample of 352 cells recorded in the hippocampus
      and parahippocampal cortex, a population of 'spatial view' cells was found to
      respond when the monkey looked at a part of the environment. The responses of
      these hippocampal neurons (i) occur to a view of space 'out there', not to the
      place where the monkey is, (ii) depend on where the monkey is looking, as shown
      by measuring eye position, (iii) do not encode head direction, and (iv) provide a
      spatial representation that is allocentric, i.e. in world coordinates. This
      representation of space 'out there' would be an appropriate part of a primate
      memory system involved in memories of where in an environment an object was seen,
      and more generally in the memory of particular events or episodes for which a
      spatial component normally provides part of the context.

PMID- 9283836
TI  - Questions of the handsurgeon to the radiologist--a survey on the most common
      lesions in the hand and the implications of diagnostic tools on their therapy.
AB  - By the rapid development of imaging techniques, a significant gap developed
      between the knowledge of the radiologists and that of the hand surgeons on
      specific indications of the different technical possibilities. The problems to be
      solved by both specialties together are analyzed. Examples of the most common
      lesions in the hand like trauma, reflex sympathetic dystrophy, congenital
      malformation, infection, tumour, rheumatoid and other degenerative processes,
      nerve compression syndromes etc., are given, and the implications of diagnostic
      tools on their therapy are discussed.

PMID- 9283837
TI  - Imaging and staging of avascular osteonecroses at the wrist and hand.
AB  - Avascular ostenecroses (AVN) are unspecific focal sceletal lesions of vascular
      origin. At the wrist, AVNs are mainly seen in the lunate (Kienbock's disease) and
      the proximal scaphoid fragment in the presence of a nonunion disease
      (pseudarthrosis). Other types of osteonecroses are rare. The natural process of
      devitalization proceeds in steps: initially, there is a bone marrow oedema,
      followed by trabecula sclerosis, cystic transformation of the spongiosa, and bone
      fragmentation. End stages include carpal collapse (SLAC wrist) and
      osteoarthritis. For imaging of the sceletal morphology in AVN computed tomography
      is most useful, whereas initial stages and perfusion damages are better detected
      with contrast enhanced magnetic resonance imaging (MRI). In this paper a staging
      classification for Kienbock's disease and the scaphoid nonunion, considering the
      diagnostic and therapeutic consequences, is presented.

PMID- 9283838
TI  - Ligamentous instabilities of the wrist.
AB  - Carpal ligament instabilities are conditions in which the individual carpal bones
      have become unstable due to abnormal ligament support. Early diagnosis of
      ligamentous wrist instabilities is important because late diagnosis or failed
      diagnosis may lead to severe complications such as osteoarthritis. This article
      reviews the most common ligamentous instability patterns of the wrist and focuses
      on how to perform and obtain radiograms which will allow reliable diagnosis of
      wrist instabilities.

PMID- 9283839
TI  - Radiologic imaging of the carpal tunnel.
AB  - Compression neuropathy of the median nerve (carpal tunnel syndrome) is the most
      common nerve compression syndrome of the extremities. Although the disease is
      usually diagnosed on the basis of clinical examination and nerve conduction
      studies, radiologic imaging plays an important role in equivocal cases and
      especially in the assessment of recurrent or unrelieved symptoms after surgical
      carpal tunnel release. While plain radiographs and computed tomography are of
      limited diagnostic value except for the evaluation of osseous carpal stenosis and
      soft tissue calcifications, high-resolution sonography and magnetic resonance
      imaging allow for direct visualization of the compressed median nerve and the
      other soft tissue structures of the carpal tunnel. Due to its excellent contrast
      resolution, magnetic resonance imaging is superior in detecting mild degrees of
      median nerve compression and in identifying potential causes of carpal tunnel
      syndrome, such as tenovaginitis of the flexor tendons or space-occupying lesions.
      However, the low cost and time requirement favor the use of sonography as the
      initial imaging study in evaluating the carpal tunnel.

PMID- 9283840
TI  - Imaging of the hand: degeneration, impingement and overuse.
AB  - Degenerative and overuse diseases as well as impingement syndromes of the hand
      are illustrated and discussed in this review article. Osteoarthritis of the
      interphalangeal joints as described by Heberden and Bouchard is a ubiquitous
      articular disease often associated with synovitis and erosive joint destruction.
      Osteoarthritis of the trapeziometacarpal joint is classified into four stages for
      proper indication of operation. Overuse can result in stenosing tenosynovitis
      around the wrist and in synovitis with or without impingement of the flexor or
      extensor tendons of the digitis or ruptures of the annular and cruciform pulleys.
      Although diagnosis of these entities is usually made by history and clinical
      investigation, ultrasound and MRI can be helpful tools in imaging of these
      diseases. Scapholunate advanced collapse (SLAC) and scaphoid nonunion advanced
      collapse (SNAC) are the characteristic degeneration pattern of the wrist and
      represent the degeneration mechanisms in scapholunate insufficiency and nonunion
      of the scaphoid. SLAC wrist is a gradual degeneration classified in three stages
      and found in posttraumatic scapholunate rupture, calcium pyrophosphate dehydrate
      deposition disease (CPPD), rheumatoid arthritis, neuropathic diseases, trauma,
      and beta 2-microglobulin associated amyloid deposition. Ulna impaction syndrome
      is increasingly recognized as a cause of ulnar sided pain and exhibits a
      characteristic MRI appearance.

PMID- 9283841
TI  - Trauma of the wrist.
AB  - In wrist injury, plain radiographs form the basis of diagnostic imaging, and can
      provide definitive answers in most cases. MR imaging is the method of choice for
      several diagnostic problem cases. These problems can include radiographically
      occult fractures where MRI enables early diagnosis compared to follow-up
      radiographs. Early stage diagnosis of a post-traumatic avascular osteonecrosis
      with high sensitivity and specificity, is only possible with MRI. In these
      instances, radiographs are only sensitive in later stages and scintigraphy is
      quite nonspecific. Stress fractures, invisible with other modalities, are also
      demonstrable with MRI. In addition, MRI is helpful in special circumstances with
      regard to non-union or pseudarthrosis. In wrist instability, radiographs in
      combination with stress views and fluoroscopy are still the initial diagnostic
      step. MRI, with the advantage of direct visualization of the wrist ligaments and
      triangular fibrocartilage complex, offers very promising results in this area.
      Generally, for the evaluation of wrist injury, MRI can be considered the most
      important second-step procedure in patients where radiographs are nondiagnostic.

PMID- 9283842
TI  - MR imaging of the carpal tunnel.
AB  - OBJECTIVE: Investigations were conducted regarding changes of carpal tunnel shape
      during wrist motion and the variations of space for the median nerve as well as
      the preoperative signs of carpal tunnel syndrome (CTS) and the postoperative
      restitution. METHODS: Axial MR images (1.0 T) were performed at the level of the
      distal radioulnar joint, pisiforme bone and hook of hamate level of 20 wrists of
      patients with clinical symptoms of CTS and further 20 wrists of volunteers. This
      was conducted with the wrist in neutral position, 45 degrees extension and 45
      degrees flexion. T2-weighted signal intensity of the median nerve were measured
      in 18 patients pre- and postoperatively. RESULTS: The increase of the cross
      sectional area of the median nerve at the pisiform level and the flattening of
      the median nerve at the hook of hamate level as well as the volar bowing of the
      flexor retinaculum at the pisiform and hook of hamate level were significantly
      greater in patients with CTS than in those with normal wrists (P < 0.05-0.001).
      In postoperative follow-up studies the distal flattening of the median nerve
      recovered in 94%. The signal intensity of the median nerve on T2-weighted images
      decreased in 67%. CONCLUSIONS: Flexion at the pisiform and hamate level as well
      as extension at the pisiform level narrows the space available for the median
      nerve potential leading to compression of the median nerve. MR imaging is
      accurate and reliable for diagnosis and postoperative follow-up of CTS.

PMID- 9283843
TI  - Pleural signs of small peripheral pulmonary masses: pathologic correlation with
      chest radiographs and diagnostic value.
AB  - OBJECTIVE: The current interest in 'cost-effectiveness' of medical imagings means
      that chest radiography is the primary radiological examination of lung diseases.
      We attempted to investigate the pathological basis of different pleural signs,
      and determine their usefulness in differentiating small bronchogenic carcinomas
      from tuberculomas by using chest radiographs. MATERIALS AND METHODS: We
      prospectively studied 30 small solitary pulmonary masses, including 24 carcinomas
      and 6 tuberculomas. All 30 resected lobe specimens were investigated with
      preoperative radiographs, postoperative specimen radiographs, 10-15 microns thick
      whole-mount sections, and 5 microns thick slices for conventional histological
      examination. To evaluate the clinical usefulness of these pleural signs, we also
      retrospectively reviewed 100 chest radiographs and conventional tomographs of 1-3
      cm peripheral pulmonary lesions, including 60 bronchogenic carcinomas and 40
      tuberculomas. RESULTS: The results confirmed that, besides the previously known
      interlobular septal fibrosis with pleural retraction, the pathologic basis also
      included the pleural puckering and adhesion with fluid collection for the 'tail'
      and 'rabbit ears' signs, and pleural dimpling with fluid collection and
      peripheral fibrous hyperplasia for the 'triangular shadow' signs. In the
      retrospective group, the pleural signs with adjacent pleural thickening was
      significantly more frequent in tuberculomas than in carcinomas (P < 0.05, chi 2
      test). CONCLUSION: Pleural signs associated with adjacent pleural thickening
      seems to contribute to differentiating granulomas from carcinomas. The
      pathological basis for this radiological finding includes visceral pleural
      fibrosis with the inflammatory cell infiltration, and the wide and shallow
      pleural dimpling filled with reactive pleural fluid.

PMID- 9283845
TI  - Metaphorically transmitted diseases. How do patients embody medical explanations?
AB  - BACKGROUND: The examination was guided by recent theories on metaphors, holding
      that our conception of the physical world in many ways derives from personal
      bodily experiences. Such experiences are fundamental to the elaboration of
      abstract structures of meaning, which, through metaphorical projections, provide
      a constitutive role in our overall comprehension of the world. It is thus to be
      assumed that patients will bring their own cluster of metaphors into the
      consultation room to structure the doctor's explanations. Our study was an
      attempt to identify some manifestations of this work of structuring and to learn
      about its consequences for interpersonal communication between patient and
      doctor. OBJECTIVE: The aim of this study was to examine how, and to what extent
      patients in a general practice understand pathoanatomical and pathophysiological
      disturbances as explanations of their illness. METHOD: The empirical basis of the
      study comprised interviews with a group of patients from a general practice, who
      were asked to narrate their understanding of medical disturbances. Based on these
      interviews we identified and classified a number of metaphors they used to
      describe bodily problems and relations. A deviating mechanical understanding of
      the body, which we characterize as ethnomechanics, was manifest in all the
      interviews. This understanding is expanded upon and its significance discussed.
      Although patients do not feel qualified to understand scientific explanations of
      their health problems, they do relate to a scientific disease mode of
      understanding. They do not, however, relate to the fine details and professional
      implications of this mode. Instead they will associate medical explanations with
      their pre-established, illness-based system of understanding through imaginative
      projections. CONCLUSIONS: Doctors need to be aware that patients possess such
      imaginative and experiential resources to make sense of medical explanations.
      Attempts to draw patients radically away from these resources may cause confusion
      and undesired breakdowns in the communication between them and their physician.

PMID- 9283844
TI  - Assessment of cervical lymph node status in head and neck cancer patients:
      palpation, computed tomography and low field magnetic resonance imaging compared
      with ultrasound-guided fine-needle aspiration cytology.
AB  - OBJECTIVE: Since the assessment of lymph node metastases in head and neck cancer
      patients remains a major problem, the findings of different imaging methods and
      the role of these methods in the clinical management are compared. MATERIAL AND
      METHODS: Palpation, computed tomography (CT) and low field magnetic resonance
      imaging (MRI; 0.1 T) are evaluated and compared with ultrasound-guided fine
      needle aspiration cytology (US-guided FNAC) prospectively in 105 consecutive
      patients with a primary cancer in the head and neck region. RESULTS: In the
      subgroup of 86 patients with palpable normal necks, CT showed lymph nodes
      fulfilling the radiologic criteria for malignancy in 27% (23/86), MRI in 17%
      (10/60) and US in 14% (12/86) of the patients US guided FNAC usually showed
      malignancy in necks containing lymph nodes with central necrosis on CT, but the
      enlarged lymph nodes that were also common on the contralateral side were often
      benign on cytology. In 5 patients, FNAC under US-guidance showed malignancy
      although none of them had lymph nodes fulfilling the radiologic criteria for
      malignancy. In the other subgroup of 19 patients with palpable metastatic necks,
      2 patients had bilateral metastases detected by all imaging methods but not by
      palpation. CONCLUSION: CT is superior to low field MRI in depicting small
      pathologic lymph nodes. Unlike lymph node structure, lymph node size is not a
      highly reliable criterion for malignancy. The findings must be correlated in
      relation to the primary disease. Since FNAC under US-guidance offers additional
      information about enlarged lymph nodes and since it can show malignancy in small
      lymph nodes not found by other methods, it can be recommended for most head and
      neck cancer patients irrespective of the use of CT or MRI.

PMID- 9283847
TI  - The family history in family practice: a questionnaire study.
AB  - OBJECTIVES: Our aims were to investigate family medical history taking in general
      practice, and to evaluate the value attached to the family medical history as an
      aid to decision making in general practice. METHOD: A postal questionnaire survey
      was conducted among all 291 GPs working within the Calderdale and Kirklees Health
      Authority area. Each questionnaire was followed by a reminder. The main outcome
      measures were answers to questions on routine and opportunistic family history
      taking and a question about transmitting knowledge about genetic risk to other
      members of the family. Questions were also posed about the value attached to the
      family medical history as an aid to decision making. RESULTS: A total of 193 GPs
      returned the questionnaire (response rate 66.3%). On registration, 94.3% of GPs
      indicated that enquiries were made about a family history of coronary heart
      disease. Breast and colorectal cancer were specifically asked about by 48.4% and
      30.7% of GPs, respectively. One-fifth of respondents indicated that they asked a
      general question about family medical history. A little over one-quarter of
      respondents indicated that they made opportunistic enquiries about the family
      history or suggested that the patient should inform other members of the family
      about possible risks. In the scenarios highlighted in this study, the majority of
      respondents felt that the family medical history had value as an aid to decision
      making. This was particularly the case for checking a patient's cholesterol
      (92.1%) and for initiating referrals in younger patients with possible cancer
      related symptoms (three-quarters of respondents). CONCLUSION: GPs value the
      family medical history as an aid to decision making. Unfortunately, apart from
      enquiries about coronary heart disease, routine or opportunistic family history
      taking is not occurring in practice. Mechanisms need to be sought to extract
      information from the family medical history so that it can be more effectively
      used by GPs.

PMID- 9283846
TI  - The impact of the October 1995 'pill scare' on oral contraceptive use in the
      United Kingdom: analysis of a general practice automated database.
AB  - OBJECTIVES: We aimed to measure the change in prescribing of oral contraceptives
      after the October 1995 UK 'pill-scare'. DESIGN: Analysis was undertaken of an
      automated database of 100 general practices (372 doctors) in England, Scotland
      and Wales which use the AAH Meditel computer system. Analysis involved two
      stages. First, we reviewed prescribing of oral contraceptives at three time
      periods: before the scare (18.10.95); the following three months (19.10.95
      18.1.96); and 3-6 months post-scare (19.1.96-18.4.96). Second, we examined the
      cohort of women on the pill at the time of the scare to assess discontinuation
      rates and pill switches after 6 months. RESULTS: Six months after the scare the
      proportion of women between 16 and 50 years of age prescribed any contraceptive
      pill decreased by only 3.5% (95% confidence limits: 2.2%-4.8%). The proportion of
      pill-users prescribed third generation pills decreased from 53.4% to 18.1%, while
      prescribing of second generation pills increased from 20.1% to 48.4%. The
      proportion of women currently on third or second generation pills at the time of
      the scare, who were no longer prescribed any pill after 6 months, was the same as
      for the equivalent period in the previous year. CONCLUSIONS: The number of women
      prescribed the pill did not alter markedly after the pill-scare. The main change
      was a switch from third to second generation pill types. In any future pill-scare
      women should be warned about the risk of pill-failure if the correct procedure
      for switching pills is not followed.

PMID- 9283848
TI  - Impaired vision in the elderly: a preventable condition.
AB  - BACKGROUND: Vision is thought to deteriorate with age as a number of factors in
      later life endanger eyesight. Assessment of the visual acuity of the elderly and
      identification of endangering factors help in detecting those with impaired
      vision which in turn impairs daily activities. OBJECTIVE: This study measured the
      visual acuity of the senior citizens and identified those with impaired vision.
      The probable contributing factors for impaired vision were studied with the aim
      of preventing visual impairment. METHOD: The study was part of a screening
      campaign for elderly glaucoma in the community. A convenience sample of
      ambulatory senior citizens from stratified localities had their visual acuity
      measured with a standard Snellen's chart. The test was repeated with pinholes if
      the visual acuity was less than 0.5. Those without improvement after pinhole were
      considered as having impaired vision. People with elevated intraocular pressure
      by the Pulsair were selected for examination by an ophthalmologist for ocular
      pathology. RESULTS: For the ambulatory population aged > or = 65 the mean visual
      acuity of either eye before pinhole was 0.3. Nearly 72% had impaired vision
      (visual acuity not corrected above 0.5 with pinhole). There was a significant
      association between this impairment and female sex, history of diabetes mellitus
      or glaucoma, cataract, and infrequent eye examination. CONCLUSION: Impaired
      vision is highly prevalent in the elderly ambulatory population, a condition
      which is preventable by tight surveillance of predisposing factors and regular
      simple measurement of visual acuity. The primary care setting is most suitable
      for these activities.

PMID- 9283850
TI  - P-R-A-C-T-I-C-A-L: a step-by-step model for conducting the consultation in
      general practice.
AB  - BACKGROUND: It has been shown that when patients are unable to express all their
      major concerns, they are less likely to follow the physician's prescribed
      treatment plan and they are less satisfied. On the other hand, the GP has a
      limited amount of time to elicit all the appropriate information and must ask
      certain questions about the biological aspects of the illness in order to carry
      out her professional responsibilities. By acting in a patient-centred way, first
      enabling the patient to express himself, the GP can make maximum use of patients'
      ability for problem formulation and solution. METHODS: We describe a model, for
      which the mnemonic, P-R-A-C-T-I-C-A-L, will help the practitioner to remember its
      nine steps. The model uses a chronological succession of strategies during the
      consultation that balances the voices of medicine and the lifeworld. In overview,
      the GP takes the patient, step by step, first through an exploration and
      clarification of his views of the illness, then expands the problem by further
      examination (e.g. the physical examination), a negotiation about the final model
      of the illness that includes both diagnosis and management, a discussion of the
      treatment plan, and finally a moment of reflection to prepare for the next visit.

PMID- 9283849
TI  - Trial of rural practice evaluation: mutual rotation by family physicians.
AB  - OBJECTIVES: We aimed to investigate the usefulness of mutual rotation by family
      physicians in providing an evaluation of rural medical practices. METHODS:
      Between June and October 1994, each of four family physicians rotated to the
      practices of the other three, where they worked as a transient locum for 4-5 days
      and evaluated each practice. They were field faculty physicians of the Department
      of Community and Family Medicine, Jichi Medical School, and based at general
      practices accredited for undergraduate and postgraduate training. Two school
      based faculty physicians also participated in the study as spare members.
      RESULTS: The rotation was conducted four times to complete the mutual rotation
      programme. There was some difference in evaluation among the practices, which
      indicated the characteristics of the practices. The evaluation accorded
      relatively well among the participants. CONCLUSIONS: Mutual rotation by family
      physicians provides an objective and practicable evaluation of general practices
      and contribute to upholding their quality, which is crucial to medical education.

PMID- 9283851
TI  - Complementary medicine: use and attitudes among GPs.
AB  - BACKGROUND: Information about use and attitudes of GPs towards complementary
      medicine is required in order to inform the debate about its place within
      mainstream medicine. There is evidence that public use of complementary medicine
      is particularly high in the South-West of England. OBJECTIVE: This study aimed to
      determine the use of, and attitudes towards, complementary medicine among GPs.
      METHODS: A questionnaire survey was performed of all primary care physicians
      working in the health service in Devon and Cornwall. RESULTS: Replies were
      received from 461 GPs, a response rate of 47%. A total of 314 GPs (68%, range 32
      85%) had been involved in complementary medicine in some way during the previous
      week. One or other form of complementary medicine was practised by 74 of the
      respondents (16%), the two most common being homoeopathy (5.9%) and acupuncture
      (4.3%). In addition, 115 of the respondents (25%) had referred at least one
      patient to a complementary therapist in the previous week, and 253 (55%) had
      endorsed or recommended treatment with complementary medicine. Chiropractic,
      acupuncture and osteopathy were rated as the three most effective therapies, and
      the majority of respondents believed that these three therapies should be funded
      by the health service. A total of 176 (38%) of respondents reported adverse
      effects, most commonly after manipulation. CONCLUSION: Over two-thirds of the GPs
      in Devon and Cornwall who responded to the survey had been involved with
      complementary medicine in some way during the previous week. This figure is
      higher than the national average. The majority of respondents believed that
      acupuncture, chiropractic and osteopathy were effective and should be funded by
      the NHS.

PMID- 9283852
TI  - Qualitative research interviewing by general practitioners. A personal view of
      the opportunities and pitfalls.
AB  - OBJECTIVE: This study looked look at the role of the GP as a qualitative research
      interviewer and aimed to illustrate areas of methodological difficulty using
      personal observations made during a qualitative study in general practice.
      METHODS AND RESULTS: The recently published literature on qualitative research in
      general practice was reviewed by the author to inform her own qualitative study
      looking at how women decide how to feed their babies. Some women in the study
      were patients of the author; some knew that she is a GP but were registered at
      another practice and some did not know that she is a doctor. In-depth and semi
      structured interviews were tape recorded and transcribed. Observations about
      combining general practice and qualitative research were recorded by the author
      in a research diary. CONCLUSION: Qualitative research is being advocated as a
      methodology appropriate for general practice, yet there are many unanswered
      questions about methodological detail. There are no guidelines to help GPs to
      decide whether it is appropriate for them to do the interviewing, the
      practicalities of doing it, and whether they should use their own patients. There
      is clearly a need for more methodological research to look at how these decisions
      influence the data and to inform GPs who are considering a qualitative study.

PMID- 9283853
TI  - A review of recently published qualitative research in general practice. More
      methodological questions than answers?
AB  - OBJECTIVE: This study aimed to review published papers which use qualitative
      interviewing in general practice as their methodology. To look specifically at
      the detail of how the methodology is presented to the reader, with particular
      emphasis on the clarity of detail about recruitment, the relationship of the
      interviewer to the respondents, the setting and how the research was presented to
      the respondents. METHODS AND RESULTS: A systematic search using Medline and hand
      searching the British Journal of General Practice, Family Practice and Social
      Science and Medicine identified 29 recent papers using qualitative interviewing
      techniques in general practice. The papers were analysed for eight methodological
      criteria by the author. A second analysis, blind to the results of the first
      analysis was performed by the author 6 weeks later. An independent assessor
      analysed 12 randomly selected papers. There was 98.3% intra-assessor agreement
      and 89.6% inter-assessor agreement about whether the eight criteria were met.
      Overall 140 of a possible 232 criteria were met (60.3%). CONCLUSION: Published
      papers using qualitative interviewing in general practice often lack explicit
      methodological detail about the relationship between the interviewer and the
      respondents, the setting, who did the recruiting and how the research was
      explained to the respondents. This methodological detail is important for the
      critical appraisal of qualitative research, where the context of the research can
      influence the data.

PMID- 9283854
TI  - Promoting clinically effective practice: general practitioners' awareness of
      sources of research evidence.
AB  - BACKGROUND: Practitioners are being encouraged to base their clinical practice on
      research evidence. In order to do this, they must be aware of and use the sources
      of evidence. METHODS: A questionnaire survey was undertaken to establish GPs'
      awareness of research evidence in their clinical practice and, in fundholding
      practices, its influence on purchasing plans. Questionnaires were sent to 360
      lead fundholders in North Thames Region and 440 of a random sample of the
      remaining general practitioners in the region for comparison. RESULTS:
      Questionnaires were returned by 62% of lead fundholders and 63% of GPs in the
      random sample. There was limited use of the electronic sources of clinical
      effectiveness. There was greater reported awareness of published sources of
      research evidence and fundholding GPs were significantly more likely to have
      referred to publications summarizing research evidence. CONCLUSIONS: GPs seem to
      make more use of published clinical effectiveness sources than the electronic
      databases. Consequently, they need educational and technical support if they are
      to make full use of the available sources of research evidence available in other
      media.

PMID- 9283855
TI  - Empowering research: statistical power in general practice research.
AB  - BACKGROUND: Statistical power is a measure of the extent to which a study is
      capable of discerning differences or associations which exist within the
      population under investigation, and is of critical importance whenever a
      hypothesis is tested by statistics. Conventionally, studies should reach a power
      level of 0.8, such that four times out of five a false null hypothesis will be
      rejected by a study. Statistical power may most easily be increased by increasing
      sample size. OBJECTIVE: We aimed to assess the level of statistical power of
      general practice research. METHODS: A total of 1422 statistical tests in 85
      quantitative original papers in the British Journal of General Practice were
      analysed for statistical power. RESULTS: The median power of tests analysed was
      0.71, representing a slightly greater than two-thirds likelihood of rejecting
      false null hypotheses. Of 85 studies, 37 (44%) attained power of 0.8 or more. Ten
      studies had power of more than 0.99 suggesting 'over-powering'. Twenty-one of the
      papers surveyed (25%) had a likelihood of gaining significant results poorer than
      that obtained by tossing a coin when a null hypothesis is false. CONCLUSION:
      While achieving higher power than studies in similar surveys of other
      disciplines, the power of general practice research falls short of the 0.8
      convention. Adequate power is essential so that effects which exist are not
      missed. Recommendations are made concerning power calculations prior to the start
      of research and reporting of results in journal articles.

PMID- 9283856
TI  - Guidelines for international collaborative research.
AB  - OBJECTIVE: As the global village becomes a reality, there is an increasing need
      to conduct international collaborative studies in family practice. A workshop at
      the WONCA meeting in Hong Kong used international attendees to produce a set of
      guidelines for international research. METHODS: At the workshop four completed
      international projects, each using a different strategy, were presented so that
      common themes might become apparent. The themes were then discussed and
      guidelines emerged from the process. RESULTS: Seven guidelines emerged for
      consideration before embarking on an international collaborative research project
      in family medicine. The guidelines deal with the characteristics of the research
      question and the importance of communication. The need for simple, brief methods
      of data collection, funding and pilot testing were identified. CONCLUSION: The
      question must be relevant to all participants to maintain interest and
      measurement tools must be validated to understand the impact of cultural
      differences in understanding.

PMID- 9283857
TI  - Selections from current literature: homocysteine: a modifiable risk factor for
      cardiovascular disease.

PMID- 9283858
TI  - An economic analysis of patients with active arterial peptic ulcer hemorrhage
      treated with endoscopic heater probe, injection sclerosis, or surgery in a
      prospective, randomized trial.
AB  - BACKGROUND: There are no published, detailed assessments of the direct costs of
      endoscopic hemostasis for actively bleeding peptic ulcers. We compared the direct
      costs of care for patients with active ulcer hemorrhage treated with endoscopic
      or medical-surgical therapies and correlated these costs with patient outcomes.
      METHODS: In a prospective, randomized, controlled trial, 31 patients with active
      ulcer hemorrhage at emergency endoscopy were randomly assigned to heater probe,
      injection, or medical-surgical treatment. For further ulcer bleeding, heater
      probe and injection patients were re-treated endoscopically and medical-surgical
      patients were referred for surgery. Direct costs were estimated using fixed and
      variable costs for resources consumed and Medicare reimbursement rates for
      physician fees. RESULTS: Compared to medical-surgical treatment, the heater probe
      and injection groups had significantly higher primary hemostasis rates (100% and
      90% vs 8%) and lower rates of emergency surgery (0% and 10% vs 75%), blood
      transfusions, and median direct costs per patient ($4153 and $5247 vs $11,149).
      Furthermore, compared to medical-surgical treatment, the heater probe group had a
      significantly lower incidence of severe ulcer rebleeding (11% vs 75%).
      CONCLUSIONS: Heater probe and injection sclerosis are similarly efficacious
      treatments for active ulcer hemorrhage, and both treatments yield significantly
      lower direct costs of medical care and cost savings.

PMID- 9283859
TI  - An assessment of the use of costs and quality of life as outcomes in endoscopic
      research.
AB  - BACKGROUND: Costs and quality of life are increasingly important study outcomes.
      We quantitatively and qualitatively assessed their use in recent endoscopic
      research. METHODS: All Medline-retrieved 1985 to 1995 published gastrointestinal
      endoscopic research using cost and/or quality of life as outcomes were analyzed.
      RESULTS: Sixty-eight (1.2%) of an estimated 5568 publications discussed costs
      and/or quality of life as endoscopic outcomes (24 quality of life, 37 cost
      effectiveness, 7 cost-benefit). Their use did not increase with time. Cost or
      quality of life was infrequently a primary study outcome. Twenty of 24 (83%)
      quality of life papers used an objective scale. However, of these, 15 of 20 (75%)
      used symptom indexes, performance scales, or other nonvalidated quality of life
      instruments. Two of 24 (8%) evaluated quality of life in nonmalignant disease.
      Eight of 40 (20%) papers claimed endoscopy was cost-effective, with no evidence
      of formal cost assessment. Ten of 32 (31%) substituted charges for costs. Of 21
      papers reporting cost data, 4 (19%) specified cost type (e.g., direct vs other),
      6 (29%) specified cost perspective, and 9 (43%) reported sensitivity analysis.
      Sixteen of 27 (59%) cost-effectiveness papers did not correlate costs with
      changes in a health outcome. CONCLUSIONS: The overall cost and quality of life
      assessment in endoscopic research has been limited and must be improved. Accurate
      cost and quality of life assessment will require cooperation between
      gastroenterologists and experts in these fields.

PMID- 9283860
TI  - Follow-up of patients with hyperplastic polyps of the large bowel.
AB  - BACKGROUND: Adenomatous colonic polyps are accepted as premalignant lesions.
      There is controversy regarding the significance of the hyperplastic polyp. The
      aim of this study was to determine the incidence of further polyps in patients
      with only hyperplastic polyps on a first colonoscopy in comparison with patients
      without polyps and with adenomatous polyps. METHODS: Ninety patients had only
      hyperplastic polyps (group I). These patients were paired according to age and
      sex with subjects having no polyps (group II) and with patients having adenomas
      (group III). RESULTS: Fifty-six patients in group I had at least one follow-up
      examination. New polyps were found in 46.4% in group I versus 15.5% in group II
      (p < 0.001) and 50% in group III (NS). In group I, 30.7% of new polyps were
      hyperplastic and 69.3% were adenomas. In fact, 32.2% of group I patients
      developed further adenomas (mean 1.5 +/- 0.8 adenomas). These adenomas occurred 1
      to 4 years after the first polypectomy (mean 2.4 +/- 0.8 years). Most of these
      adenomas were small and tubular, but 16.6% were villous or had severe dysplasia.
      CONCLUSION: Patients with hyperplastic polyps were 2.4 times more likely to have
      further adenomas than were those without polyps.

PMID- 9283861
TI  - Distal hyperplastic polyps do not predict proximal adenomas: results from a
      multicentric study of colorectal adenomas.
AB  - BACKGROUND: The association between distal hyperplastic polyps and proximal
      adenomas is still a matter of debate. We investigated this association while
      taking into account patient characteristics. METHODS: After exclusion of patients
      with inflammatory bowel diseases, familial adenomatous polyposis, or any cancer,
      3088 eligible consecutive subjects aged 18 to 69 years underwent total
      colonoscopy in four gastroenterology units. The odds ratios (OR) of having
      proximal adenomas according to patient characteristics (age, sex, medical center,
      year of endoscopy, reasons for referral, and distal findings) were estimated in
      univariate and multivariate analyses. RESULTS: Patients with distal polyps of any
      type showed an adjusted OR of 2.5 (95% CI [1.9, 3.1] p < .001) of having proximal
      adenomas as compared with those without distal polyps. When distal adenomas and
      distal hyperplastic polyps were included in the multivariate model as independent
      factors, the presence of adenomas significantly increased the risk of proximal
      adenomas (OR = 2.8: 95% CI [2.2, 3.6] p < .001), whereas the presence of
      hyperplastic polyps did not (OR = 1.1: 95% CI [0.8, 1.5] p = .64). No association
      with number, size, or location of distal hyperplastic polyps was seen.
      CONCLUSIONS: Our data show that the presence of hyperplastic polyps should not be
      the sole indication for total colonoscopy because they are not associated with
      proximal adenomas when adjusting for patient characteristics and presence of
      distal adenomas.

PMID- 9283862
TI  - The pigment of melanosis coli: a lectin histochemical study.
AB  - BACKGROUND: The compositional nature of the pigment of melanosis coli is
      essentially unknown. Previous histochemical studies suggested that this pigment
      has certain similarities with lipofuscin (i.e., age-dependent pigment) and
      ceroids (i.e., pathologically derived pigments) and that it may contain,
      therefore, polymerized glycolipids and glycoproteins. However, the saccharide
      composition of this pigment was never explored by lectin histochemical
      procedures, which was the main object of this study. METHODS: Colonoscopic biopsy
      specimens from eight patients with melanosis coli and from three normal control
      subjects were studied by fluorescent microscopy and by standard and lectin
      histochemistry. The number of apoptoses in the lining colonic epithelium was also
      evaluated histologically. RESULTS: Apoptotic bodies were significantly more
      numerous in patients with melanosis coil than in control subjects. The pigment
      that accumulates in macrophages of the lamina propia showed autofluorescence,
      sudanophilia, acid-fastness, and positiveness to PAS and Schmorl's reactions, all
      of which are common to lipofuscin and ceroids, plus an intense argentaffin
      reaction abolished by bleaching, indicative of a melanic substance. Lectin
      histochemistry showed, in decreasing order of frequency, the presence of alpha-D
      mannose, sialic acid, beta-D-galactose (lactose), gal-beta-(1-3)acetyl
      galactosamine, alpha-D-galactose, and alpha-L-fucose, but no terminal alpha-D
      acetyl-galactosaminyl residues. CONCLUSIONS: The significant increase of
      apoptotic bodies in the lining colonic epithelium indicated that this type of
      cell death is not due to the natural programmed cell renewal, but to the action
      of laxatives. Because the autofluorescent pigment of melanosis coli contains
      melanin (as well as glycoconjugates) and is not dependent on age but on the use
      of anthranoid laxatives, it should be categorized as a "melanized ceroid." The
      lectin affinities of this pigment indicated that it contains a substantial number
      of saccharide residues almost similar to those found in the ceroid pigment of
      human aortic atheromas. These findings and considerations on the metabolism and
      pharmacokinetics of anthranoids suggested that the apoptotic epithelial cells,
      rather than the laxatives, may be the source of the pigment saccharides, whereas
      the precursors of the melanic substance may be derived from the anthranoids.

PMID- 9283863
TI  - A prospective, double-blind trial of L-hyoscyamine versus glucagon for the
      inhibition of small intestinal motility during ERCP.
AB  - BACKGROUND: Glucagon is often used to inhibit duodenal motility and enhance
      cannulation during ERCP. Levsin is an antimuscarinic, anticholinergic agent that
      may be as effective as glucagon. METHODS: Three hundred eight patients requiring
      an antimotility agent during ERCP were randomized in a double-blind prospective
      study to intravenous Levsin or glucagon. Parameters recorded included difficulty
      of procedure, predrug and postdrug motility grade, effectiveness of medication,
      patients requiring "crossover" drug, side effects, and cost per case. RESULTS:
      One hundred fifty-three patients were randomized to glucagon and 155 to Levsin.
      The two groups were equally matched with regard to patient and procedure
      characteristics. Of statistical significance were the following: (1) 12 patients
      in the Levsin group required crossover compared to 1 patient in the glucagon
      group, (2) Levsin was slightly less effective in inhibiting motility, but this
      did not adversely influence procedure difficulty, (3) Levsin was associated with
      more minor side effects (nausea, vomiting, and pain) at 2 hours after the
      procedure (Levsin 36 of 143, glucagon 24 of 152, p = 0.045) but there was no
      difference in pancreatitis (glucagon 6, Levsin 8), (4) Levsin was associated with
      a significant cost advantage (Levsin $10.45/case, glucagon $29.51/case, p <
      0.001). CONCLUSION: Levsin may provide a reasonable alternative antimotility
      agent during ERCP. Levsin does not appear to alter the rate of significant
      postprocedure complications. The cost benefit advantage appears to be
      substantial.

PMID- 9283864
TI  - Therapeutic ERCP: a cost-prohibitive procedure?
AB  - BACKGROUND: ERCP is increasingly being performed for therapeutic purposes and
      engenders a proliferation of disposable equipment without a clear indication of
      cost-effectiveness. METHODS: We analyzed the financial impact of ERCP by
      prospectively analyzing ERCPs performed in our institution from June 1, 1994, to
      September 30, 1994, by calculating charges related to indirect costs, disposable
      equipment costs, and overall reimbursement. The data were analyzed according to
      insurance payor as well. RESULTS: Disposable equipment costs a mean of $149 per
      diagnostic ERCP and $532 per therapeutic ERCP. For diagnostic ERCP, disposable
      equipment accounted for 27% of reimbursement; for therapeutic ERCP, disposable
      equipment accounted for 68% of reimbursement. Although overall reimbursement was
      higher for therapeutic ERCP, the very high direct costs related to disposable
      equipment limited the ability of reimbursement to cover indirect costs.
      CONCLUSIONS: Depending on the complexity of cases, quantity of disposable
      equipment used, and patient-insurance mix, therapeutic ERCP may be cost
      prohibitive for a given endoscopy unit. Indirect costs should be more carefully
      and quantitatively analyzed. Disposable equipment should be evaluated in terms of
      cost, safety, and patient outcome.

PMID- 9283865
TI  - High-resolution endoluminal sonography is a sensitive modality for the
      identification of Barrett's metaplasia.
AB  - BACKGROUND: The "gold standard" and only accurate method for diagnosing Barrett's
      esophagus is by esophagogastroduodenoscopy with biopsy. We evaluated the ability
      of high-resolution endoluminal sonography (HRES) to detect the mucosal changes in
      Barrett's esophagus. METHODS: Seventeen patients with documented Barrett's and 12
      normal controls underwent endoscopy with HRES examination using a 20 MHz
      ultrasound transducer to evaluate for mucosal changes. HRES examinations were
      videotaped then reviewed by an unblinded investigator to identify criteria
      possibly diagnostic of Barrett's and then by a blinded investigator to test the
      validity of these criteria. Barrett's was diagnosed by HRES if the second
      hypoechoic layer appeared thicker than the first hyperechoic layer of the mucosa.
      Normal mucosa was defined as having a pencil-thin second hypoechoic layer on
      HRES. Measurements of the second hypoechoic layer were made using a computer and
      compared in patients with Barrett's and patients with normal esophagus. RESULTS:
      All 17 patients with Barrett's were correctly identified by HRES (sensitivity
      100%). Ten of 12 controls were correctly identified as normal (specificity 86%).
      There was good correlation between HRES and pathologic diagnoses (r 0.86). The
      second hypoechoic layer was significantly thicker in Barrett's patients than in
      normal controls (p < .001). CONCLUSIONS: HRES is a sensitive new method for
      identifying Barrett's esophagus. However, dysplasia could not be identified by
      HRES in this study.

PMID- 9283866
TI  - In vitro effects of simulated gastric juice on swallowed metal objects:
      implications for practical management.
AB  - BACKGROUND: Swallowed metal objects often pose a technical challenge for the
      endoscopist. We studied in vitro the effects of simulated gastric juice on metal
      objects commonly encountered in endoscopic practice and measured the physical
      chemical changes. METHOD: Razor blades, disc batteries, and pennies were
      incubated in simulated gastric juice at 37 degrees C. The weights of the objects
      were recorded hourly. When no change could be detected, the solution was
      subjected to mass spectrometry to verify absence of effect. The findings were
      correlated with clinical observation in one patient who swallowed razor blades
      repeatedly. RESULTS: Dissolution of the razor blade was proportional to the
      duration of acid immersion. At 24 hours, the blades weighed 63% of the original
      weight. Double-edged razor blades could be broken with a snare at 15 hours. The
      thickened back of the single-edged blade totally dissolved in 2 hours. No leak of
      contents could be detected with disk batteries. Pennies were unaffected.
      CONCLUSION: Corrosion of razor blades occurs rapidly in the normal stomach.
      Within 24 hours double-edged blades become fragile and can be broken with a
      snare. This observation may guide the timing of endoscopic removal. Modern disk
      batteries are acid resistant for 24 hours.

PMID- 9283867
TI  - Use of the 25 mm flanged esophageal Z stent for malignant dysphagia: a
      prospective multicenter trial.
AB  - BACKGROUND: An initial multicenter study using a 21 mm flanged esophageal Z stent
      demonstrated excellent palliation but an 11% immediate complication rate at
      placement and a 27% migration rate at 1 month. This North American multicenter
      trial prospectively studied a 25 mm flanged Z stent to define its palliative
      ability and whether the increased diameter affected placement or migration
      problems. METHODS: Fifty patients who had esophageal Z stents at seven university
      or regional referral hospitals were prospectively studied. Indications for
      prosthesis placement, previous therapy, patient demographics, incidence of
      concomitant tracheoesophageal fistula, and degree of dysphagia were defined, as
      were procedural and subsequent stent-related problems, survival times, the
      ability to occlude a tracheoesophageal fistula, and subsequent degree of
      dysphagia. RESULTS: Twenty-four patients had infiltrating malignancy (16
      exophytic and 10 extrinsic), 9 of whom had concomitant tracheoesophageal
      fistulas. Ten patients (20%) had misplaced stents requiring retrieval and
      replacement, 12 patients (24%) had subsequent stent-related problems including
      exsanguination (2), aspiration (3), tumor overgrowth (3), and postplacement
      migration (4) (8%). There was statistically significant improvement in prestent
      versus poststent dysphagia and two thirds of patients had complete occlusion of
      their tracheoesophageal fistula. CONCLUSIONS: Redesign of the esophageal Z stent
      has decreased the migration rate without increasing placement or subsequent
      erosion problems. Its efficacy appears comparable to the currently marketed Z
      stent for the palliation of malignant dysphagia and occlusion of
      tracheoesophageal fistula.

PMID- 9283868
TI  - Duodenal obstruction caused by pancreatic head carcinoma: palliation with self
      expandable endoprostheses.
AB  - BACKGROUND: The risks of palliative operative intervention of gastric outlet
      obstruction for advanced pancreatic head carcinoma has been reported to be quite
      high. The present study reports the results of attempted endoscopic palliation of
      duodenal obstruction in these patients. METHODS: Ten patients with endoscopically
      documented malignant duodenal strictures from pancreatic head carcinoma in whom
      self-expandable endoprostheses were placed are retrospectively analyzed. In three
      patients with jaundice, biliary stents were also placed. Standard esophageal type
      (not membrance coated) Wallstent self-expandable endoprostheses were used.
      PATIENTS: Gastric outlet obstruction was relieved in all patients after
      implantation of duodenal endoprostheses, and jaundice was palliated in those with
      additional biliary obstruction after bile duct stenting. One case of gastric
      ulceration was the major complication. No recurrence of gastric outlet
      obstruction was noted in the follow-up period of 1 to 5 months. CONCLUSION: The
      preliminary data suggest that self-expandable duodenal endoprostheses can
      effectively relieve gastric outlet obstruction in patients with advanced
      pancreatic head carcinoma.

PMID- 9283869
TI  - Usefulness of contrast-enhanced endoscopic ultrasonography with intravenous
      injection of sonicated serum albumin.

PMID- 9283870
TI  - A transparent hood simplifies magnifying observation of the colonic mucosa by
      colonoscopy.

PMID- 9283871
TI  - Endocrine neoplasm arising from duodenal heterotopic pancreas: a case report.

PMID- 9283872
TI  - The endoscopic ultrasonographic appearance of Brunner's gland hamartoma.

PMID- 9283873
TI  - Dilation of a difficult benign pancreatic duct stricture using the Soehendra
      stent extractor.

PMID- 9283874
TI  - The whirlpool jet technique for removal of pancreatic duct ascaris.

PMID- 9283875
TI  - Radiation-induced jejunal mucosal vascular lesions as a cause of significant
      gastrointestinal hemorrhage.

PMID- 9283876
TI  - Enteroscopic diagnosis of bleeding jejunal phlebectasia: a case report and review
      of literature.

PMID- 9283877
TI  - Managed care and endoscopy.

PMID- 9283878
TI  - Endoscopy in crisis: the challenge of new technology.

PMID- 9283879
TI  - Feeding jejunostomy button replacement.

PMID- 9283880
TI  - Where does gastric leiomyosarcoma originate?

PMID- 9283881
TI  - Colonoscopic removal of chicken bones impacted in the sigmoid in two patients.

PMID- 9283882
TI  - Balloon extraction of an impacted meat bolus after argon beam coagulation.

PMID- 9283883
TI  - Ring-like elevations in the colon associated with the colonoscopic suction.

PMID- 9283884
TI  - Alterations in pancreatic ductal morphology following polyethylene pancreatic
      stent therapy.

PMID- 9283885
TI  - Injection of fibrin tissue adhesive versus laser photocoagulation in the
      treatment of high-risk bleeding peptic ulcers: a controlled randomized study.

PMID- 9283886
TI  - Collagenous colitis: a retrospective study of clinical presentation and treatment
      in 163 patients.

PMID- 9283897
TI  - Increased expression of c-myc p67 oncoprotein in patients with myelodysplastic
      syndromes in transformation to acute leukaemia.
AB  - Thirty-five patients, 24 males and 11 females, with myelodysplastic syndromes
      were studied for the expression of c-myc encoded p67 oncoprotein. According to
      FAB classification, 5 patients had refractory anaemia (RA). 5 refractory anaemia
      with ringed sideroblasts (RARS), 17 refractory anaemia with excess of blasts
      (RAEB), 4 refractory anaemia with excess of blasts in transformation (RAEB-t),
      and 4 chronic myelomonocytic leukaemia (CMML). The mouse anti-human 9E10 derived
      monoclonal antibody in the standard APAAP technique for immunohistochemical
      analysis was used. A scoring method similar to that routinely used for endogenous
      neutrophil alkaline phosphatase estimation, was applied to obtain parametrically
      comparable results. In all but two MDS patients, the observed c-myc oncoprotein
      score values did not differ statistically from those found in the controls. The
      values did not correlate with peripheral blood or bone marrow blast cell numbers.
      In two out of 17 patients with RAEB in whom very high c-myc score values were
      found, acute non-lymphocytic leukaemia (ANLL) was diagnosed 30 and 45 days later,
      respectively. Furthermore, we found high c-myc score values in three patients
      with RAEB and in two patients with RAEB-t during the ANLL phase which was
      diagnosed six to ten months after the initial study. Our data suggest that c-myc
      activation may be seen in all cases of MDS in overt ANLL phase, and also in some
      RAEB patients a few weeks before diagnosis of overt ANLL. The possible prognostic
      value of c-myc activation in MDS patients remains to be clarified.

PMID- 9283898
TI  - Leukaemia phenotype and ethnicity in children living in the United Arab Emirates.
AB  - Immunophenotyping was carried out in the presentation bone marrow samples of 32
      children with acute lymphoblastic leukaemia (ALL), living in the UAE. Twenty two
      had B-cell precursor ALL, 10 had T-cell precursor leukaemia. Clinical features
      were in accordance with internationally reported series. Analysis of ethnic
      origin showed that children of subcontinental origin (Indian and Pakistani) had a
      significantly higher proportion of T-cell ALL than their Arabic counterparts.
      This may reflect an interim phase in the pattern of ALL, between those of the
      developing and industrialized countries.

PMID- 9283899
TI  - Rare inherited coagulation disorders in India.
AB  - Twenty four cases with rare coagulation disorders were diagnosed over a 4 year
      period. These included 8 patients with factor X deficiency, 7 with factor XIII
      deficiency, 4 each with fibrinogen and factor VII deficiency and 1 with factor V
      deficiency. All these patients had presented with bleeding manifestations. Two
      patients with factor X deficiency showed interesting clinical presentations, one
      patient had recurrent deep vein thrombosis and another patient had a pseudotumor
      of the thigh.

PMID- 9283900
TI  - Angioimmunoblastic lymphadenopathy (AILD) with benign course.
AB  - A group of rare systematic lymphoproliferative disorders have been described
      under the heading of angioimmunoblastic lymphadenopathy with dysproteinaemia
      (AILD), from purely reactive to bona fide malignancies. Some patients exhibit a
      benign form of disease, but most exhibit an aggressive form with high mortality
      rate. We present two elderly patients with prominent constitutional symptoms,
      generalized lymphadenopathy, hepatosplenomegaly, diffuse maculopapular rash,
      polyclonal hypergammaglobulinaemia and immunohaemolytic anaemia. Lymph node
      biopsies showed features consistent with the diagnosis of AILD. The patients were
      treated with steroid and they are in complete remission 3.5 and 2.5 years,
      respectively after the diagnosis has been established.

PMID- 9283901
TI  - Blast colony forming cells in umbilical cord blood: frequency and correlation to
      other haemopoietic progenitors.
AB  - Umbilical cord blood has been suggested as a potential source of haemopoietic
      stem cells for clinical transplantation. Assay of stroma adherent blast colony
      forming cells (CFU-BL), as a cell type that may predict marrow repopulation, has
      already been suggested to predict the outcome of bone marrow transplantation. In
      the present experiments the frequency of CFU-BL in plastic non adherent
      mononuclear cell fraction (PNAMNC) of umbilical cord blood was studied. If PNAMNC
      from cord blood was co-incubated with a pre-established stromal layer from normal
      bone marrow a strict linear correlation between panned PNAMNC and blast colonies
      were observed. Frequency of CFU-BL in cord blood was significantly lower than
      that in bone marrow. In cord blood, CFU-GEMM frequency was found to be comparable
      to that of bone marrow, CFU-GM and BFU-E frequency was reduced. A good
      correlation between CFU-BL and BFU-E frequency was found both in cord blood and
      bone marrow. On the other hand, irrespective of their source, correlation between
      CFU-BL and CFU-GEMM or CFU-GM was weak.

PMID- 9283902
TI  - Methods to measure cell proliferation in haematology.

PMID- 9283903
TI  - The first 15 minutes of hemodialysis does not affect platelets.
AB  - In the study, platelet count and volume, granulocyte number, binding of
      monoclonal antibodies to platelet glycoproteins Ib and IIb/IIIa were evaluated in
      hemodialyzed patients. Exclusively, the granulocyte count dropped significantly
      at 15 minutes after the initiation of dialysis as compared to predialysis
      samples. It seems that contemporary used cuprophane dialyzer membrane is more
      biocompatibile and does not have major impact on platelets.

PMID- 9283904
TI  - Does oxypentifylline reduce the intensity of acute graft-versus-host disease
      following allogeneic bone marrow transplantation?
AB  - From 1988 to 1993, a retrospective analysis of the severity of acute graft-versus
      host disease (GVHD) was carried out in two groups of patients undergoing
      allogeneic bone marrow transplantation for various haematological disorders. One
      group of 23 patients received oxypentifylline in a dose of 400 mg, 6 hourly,
      orally, day -10 to day +35 in addition to other standard management received by
      the control group of 20 patients. Acute GVHD was scored in each patient according
      to the Seattle criteria. Patients receiving oxypentifylline showed a lower GVHD
      score in each organ-specific area and this reached significance with the total
      GVHD score. A significantly smaller proportion of patients in the treatment group
      developed acute GVHD of grade 2 or more. It is concluded that oxypentifylline
      used in the present dosage reduces the intensity of acute GVHD following
      allogeneic bone marrow transplantation and is also well tolerated by the patient.

PMID- 9283905
TI  - The in vitro culture of human bone marrow and peripheral blood cells in the study
      of haemolymphopoiesis. A historical review.

PMID- 9283906
TI  - Xenogeneic transfer of fetal liver and adult bone marrow-derived haemopoietic
      cells in rodents: changes in spleen colony differentials with increased doses of
      cells.
AB  - The effect of very high haemopoietic cell doses were investigated on the
      composition of splenic cell colonies/clusters in irradiated animals under
      xenogeneic circumstances. Differential cluster/colony counts from serial
      histological sections of the spleen were investigated before, and 9-12 days after
      transplantation of fetal liver- or adult bone marrow-derived haemopoietic cells
      following 5.0 to 8.5 Gy total body irradiation. Syngeneic as well as xenogeneic
      (mouse to rat and rat to mouse) transplantations were carried out. Cluster/colony
      differentials changed with the increase of the injected cell mass from 10(5) to
      10(6) and 10(7) or more, i.e. the overwhelming erythroid pattern became trilinear
      even with xenogeneic transplants.

PMID- 9283907
TI  - Fibronectin increases both non-adherent cells and CFU-GM while collagen increases
      adherent cells in human normal long-term bone marrow cultures.
AB  - Normal haematopoietic proliferation and differentiation occur within the human
      bone marrow microenvironment which is comprised of stromal cells including
      fibroblasts, adipocytes, macrophages and endothelial cells as well as the
      extracellular matrix made of collagen, fibronectin, laminin, vitronectin,
      thrombospondin and haemonectin. All haematopoietic progenitor cells including
      primitive LTC-IC, multilineage CFU-mix, myeloid CFU-GM and erythroid BFU-E adhere
      to the heparin-binding domains of the extracellular matrix component fibronectin.
      Human long-term bone marrow cultures (LTHBMC) represent the best available
      approximation for the in vivo marrow microenvironment in which the proliferation
      and differentiation of haematopoietic progenitor cells depend on the presence of
      marrow stromal cells and their attendant matrices. Since extracellular matrix
      components have been shown to promote myelopoiesis in long-term murine bone
      marrow cultures, we have examined the effect of two main components of the
      extracellular matrix: fibronectin and collagen type I on myelopoiesis in LTHBMC
      in an effort to increase the myeloid progenitor cell production. The present
      study revealed different modulatory effects for these two components. Collagen
      significantly increased the adherent fraction of LTHBMC (p < 0.05) but always
      resulted in a decreased myeloid progenitor cell (CFU-GM) production throughout
      the whole 8 weeks of culture. On the other hand, fibronectin significantly
      increased the number of both non-adherent cells. CFU-GMs (p < 0.01) and to a
      lesser extent the number of adherent cells as well as maintaining the LTHBMC up
      to 14 weeks. Fibronectin has been previously shown to stimulate the development
      of CFU-GMs in short-term semisolid cultures and to play an active role in
      haematopoietic progenitor cell-microenvironment interactions. Therefore, the
      presence of fibronectin in LTHBMC could increase both the productivity and
      longevity of myelopoiesis in the system. The integration of fibronectin in the ex
      vivo expansion systems currently undergoing development would ensure a sustained
      effective cumulative production of the myeloid progenitor cells (CFU-GMs), and
      consequently could accelerate the rate of haematological recovery in transplanted
      patients.

PMID- 9283908
TI  - The significance of trilineage myelodysplasia in de novo acute myeloblastic
      leukemia: clinical and laboratory features.
AB  - A prospective study was undertaken to elucidate the clinical and laboratory
      differences between de novo acute myeloid leukemia (AML) and AML with trilineage
      myelodysplasia (AML-TMDS). One hundred and seven patients with AML were diagnosed
      at the University Hospital between January 1987 and July 1992, and were followed
      until July 1995. TMDS was identified in 17 of them (16%). With regard to age and
      sex distribution no difference was found between AML patients with and without
      TMDS (p = 0.43, p = 0.54, respectively). The duration of symptoms at presentation
      in AML-TMDS was similar to those observed in de novo AML (p = 0.29). Hemoglobin
      values and platelet counts were similar in both groups of patients (p = 0.45, p =
      0.44, respectively). However, peripheral white blood cell and neutrophil counts,
      as well as blast counts in AML-TMDS patients were lower than those observed in
      AML without TMDS patients (p < 0.001 for all of them). Bone marrow blast counts
      in de novo AML were higher than the values observed in AML-TMDS patients (p <
      0.001). TMDS occurred predominantly in M2 and M6 FAB types, and was absent in the
      M3 type. Bone marrow histology showed no particular feature that could be of
      diagnostic relevance. The remission rates were similar in both groups of patients
      (p = 0.55). The same was true for the probability of disease-free survival and
      overall survival during the period of study (p = 0.50, p = 0.33, respectively).
      These results suggest that: 1) in AML-TMDS patients, leukemia transformation
      occurs in a more undifferentiated pluripotent stem cell, leading to a dysplastic
      residual hemopoiesis besides the blast proliferation; 2) the incidence of TMDS in
      our group of patients did not influence the clinical outcome after treatment of
      the disease.

PMID- 9283909
TI  - Ultrastructural study on the in vitro interaction between haemopoietic cells and
      stromal cells. A new method using gel technique.
AB  - The ultrastructural study of the interaction between stroma and haemopoiesis is
      not an easy task because the loose attachment may be damaged during manipulation.
      This paper describes a technique by which the loose connection between
      preestablished stromal layer and attached haemopoietic cells (derived from blast
      colony forming cells) can be preserved and studied ultrastructurally. Stromal
      cultures were obtained from human bone marrow cells. Blast colony forming cells
      were studied by co-incubating the stroma with fetal calf serum supplemented
      McCoy's medium containing bovine plasma, thrombin and calcium to form a gel
      ('plasma clot'). Colony formers attached to the stroma formed myeloid colonies
      within 6 days. The semisolid plasma clot which solidifiers rapidly on the
      addition of glutaraldehyde or formaldehyde entraps the blastic colonies and
      haemopoietic cells in their position. Even the non-attached or mobile cells can
      be entrapped by this technique. The immature cells were found to be attached to
      the stromal surface and/or to the extracellular matrix, while the more mature
      cells migrated either to the surface of the colony or attached to the non-covered
      areas of the plastic surface. This method may offer a special technique to study
      dynamic interactions in other situations (e.g. chemotaxis etc.), too.

PMID- 9283910
TI  - Iron overload in light of the identification of a haemochromatosis gene.
AB  - This review gives a short summary of the most recent advances in the regulation
      of iron at the molecular level. The clinical consequences of iron overload are
      discussed and a critical evaluation of the assays used for the estimation of the
      body iron status provided. The methodology of the search for a candidate gene for
      hereditary haemochromatosis is described and the results critically evaluated.
      The importance of widespread population surveys by PCR-based screening tests for
      the most likely disease-associated mutation is stressed as a means of early
      diagnosis of hereditary haemochromatosis, enabling prevention of the development
      of Life-threatening complications of iron overload.

PMID- 9283911
TI  - Infradiaphragmatic Hodgkin's disease.
AB  - Between 1968 and 1994, 133 patients with stages I and II supradiaphragmatic
      Hodgkin's disease were evaluated at our institution. During the same period we
      treated only 11 patients with stages I and II infradiaphragmatic Hodgkin's
      disease. When compared to patients with disease above the diaphragm, patients
      with Hodgkin's disease below the diaphragm were more frequently male (p < 0.05),
      were generally older (46.3 vs 40.1 years, but the difference was not
      significant), had a higher incidence of systemic symptoms (p < 0.05), and had
      predominantly histologic subtypes with mixed cellularity and lymphocyte
      predominance. Primary treatment included inverted Y radiotherapy in 3 patients,
      polychemotherapy in 6, and combined treatment in 2. Ten patients achieved
      complete response. Five- and ten-year survival rates were 90% and 67.5%,
      respectively. There was no difference in survival rate between patients with
      infradiaphragmatic and supradiaphragmatic Hodgkin's disease receiving similar
      treatment.

PMID- 9283912
TI  - Inhibition of mitogen-induced cellular cytotoxicity by serum from patients with
      multiple myeloma.
AB  - Mitogen-induced cellular cytotoxicity (MICC) of peripheral blood mononuclear
      cells (PBMCs) against K562 cell targets was assessed in 24 patients with multiple
      myeloma (MM) using the 24 hours 51Cr-release assay. We found that PBMCs from MM
      patients exhibited normal MICC values when cells were isolated, washed and
      cultured in vitro in the absence of patients' serum. Patients' serum inhibited
      MICC of normal PBMCs stimulated by PHA. A strong positive correlation was found
      between percentages of inhibition and the amount of serum paraprotein in the
      patients studied, suggesting that paraprotein should be the main inhibitory
      component in this model of cytotoxicity. The possible inhibitory effect of serum
      paraprotein of MM patients on other types of cellular immunity remains to be
      elucidated.

PMID- 9283913
TI  - Aplastic anemia in eosinophilic fasciitis: responses to immunosuppression and
      marrow transplantation.
AB  - Eosinophilic fasciitis (EF) is a rare connective tissue disorder which is
      frequently associated with hematologic disorders, especially aplastic anemia (AA)
      and variants (amegakaryocytic thrombocytopenia). The prognosis for AA with EF has
      generally been poor, but a few reports suggest a role for immunosuppressive
      therapy. We have seen four cases of AA complicating EF. All received
      corticosteroids and anti-thymocyte globulin without any benefit. One patient died
      of bleeding and infection. A second achieved unmaintained partial remission after
      two courses of cyclosporine A, although he had difficulty with side effects. Two
      patients received bone marrow transplants and both initially engrafted well. One
      had received marrow from a phenotypically HLA-matched parent and died of late
      graft failure. The second transplanted patient appears to be the only reported
      case of long term cure of both the AA and EF. Our four patients constitute the
      largest reported series of AA with EF and shed light on clinical aspects of the
      disease, and on the pathogenesis, particularly on responsiveness to different
      therapies; furthermore, there are implications to the treatment of AA in general.

PMID- 9283914
TI  - Calibration of clot-based, coagulation factor assays using a first-order
      exponential equation and the method of nonlinear least squares.
AB  - A nonlinear mathematical model has been developed which relates the time to
      calcium-initiated formation of a detectable clot in citrated, factor-deficient
      plasma to the clotting activity of the factor deficient in the plasma. The data
      of clot-based factor assays fit well the exponential expression of this scheme,
      which can be used conveniently in the clinical laboratory to calibrate the
      clotting activity of individual coagulation factors in samples of citrated
      plasma. Aside from its clinical utility, the model may prompt the formulation of
      testable hypotheses not otherwise prompted by the existing, empiric approach to
      the quantitation of coagulation factor activity.

PMID- 9283915
TI  - The importance of Lp(a)-fibronectin interaction in atherogenesis.
AB  - An elevated concentration of lipoprotein (a) (Lp(a)) in serum has been considered
      a risk factor for coronary heart disease by various investigators. The apo(a)
      portion of Lp(a) binds to the carboxyterminal heparin binding domain of
      fibronectin. Lp(a) bound to fibronectin is internalized through the fibronectin
      receptor pathway and thereby causes increased accumulation of lipid and foam cell
      formation. In the present study, fibronectin and Lp(a) concentrations have been
      assayed in patients with coronary heart disease (CHD) and healthy subjects. Serum
      total cholesterol, triglyceride, LDL, VLDL and HDL cholesterol levels in patients
      with coronary heart disease were significantly different from the control group
      (p < 0.001). Plasma fibronectin (p < 0.05) and serum Lp(a) (p < 0.001) levels
      were found to be significantly elevated when compared with the control group.

PMID- 9283916
TI  - Classification of malignant lymphomas: the updated Kiel classification.

PMID- 9283917
TI  - Leukaemia cutis preceding acute myelomonocytic leukaemia.
AB  - We report a case of acute myelomonocytic leukaemia (AMML) who presented with a
      striking leukaemic infiltration in the frontal area of the scalp that was also
      rapidly followed by infiltrates in other sites of the skin, mainly in the upper
      thoracic wall. Leukaemic skin infiltration developed independently of his
      haematological status; nevertheless, he rapidly progressed to acute leukaemia. We
      emphasise the importance of early recognition and identification of such lesions
      with a subsequent early application of systematic antileukaemic therapy.

PMID- 9283918
TI  - Severe anemia due to Kell alloimmunization.
AB  - A case of alloimmunization in pregnancy caused by antibody to Kell red blood cell
      antigen is described. The baby was born prematurely with severe anaemia (HB
      3g/dL). He was the 5th child of the family. The mother, who was found blood group
      O, Rh D positive, received at the age of 18 years a blood transfusion. This case
      emphasizes the importance of serological screening for low frequency red cell
      antigens, particularly in the case of a positive indirect Coomb's test in Rh
      positive pregnant mothers.

PMID- 9283919
TI  - Long-term survival in a case of high-risk type IgD myeloma; a possibility of
      effectiveness of interferon-alpha and erythropoietin.
AB  - The prognosis of patients with IgD myeloma is poorest among all types of multiple
      myeloma. We report a case of a patient with IgD myeloma who survived for an
      extraordinarily long period post-diagnosis (65 months). According to the new risk
      grouping of IgD myeloma (Shimamoto Y. et al., Eur. J. Haematol. 47, 262 (1991),
      he was classified as being in the high-risk group, with a zero percent expected 5
      yr survival. Nevertheless, he survived for 65 months. We discuss the usefulness
      of interferon-alpha and erythropoietin for the treatment of IgD myeloma.

PMID- 9283920
TI  - Whole blood coagulation analyzers.
AB  - Whole blood Coagulation analyzers (WBCAs) are widely used point-of-care (POC)
      testing devices found primarily in cardiothoracic surgical suites and cardia
      catheterization laboratories. Most of these devices can perform a number of
      coagulation tests that provide information about a patient's blood clotting
      status. Clinicians use the results of the WBCA tests, which are available minutes
      after applying a blood sample, primarily to monitor the effectiveness of heparin
      therapy--an anticoagulation therapy used during cardiopulmonary bypass (CPB)
      surgery, angioplasty, hemodialysis, and other clinical procedures. In this study
      we evaluated five WBCAs from four suppliers. Our testing focused on the
      applications for which WBCAs are primarily used: Monitoring moderate to high
      heparin levels, as would be required, for example, during CPB are angioplasty.
      For this function, WCBAs are typically used to perform an activated clotting time
      (ACT) test or, as one supplier refers to its test, a heparin management test
      (HMT). All models included in this study offered an ACT test or an HMT.
      Monitoring low heparin levels, as would be required, for example,during
      hemodialysis. For this function, WBCAs would normally be used to perform either a
      low-range ACT (LACT) test or a whole blood activated partial thromboplastin time
      (WBAPTT) test. Most of the evaluated units could perform at least one of these
      tests; one unit did not offer either test and was therefore not rated for this
      application. We rated and ranked each evaluated model separately for each of
      these two applications. In addition, we provided a combined rating and ranking
      that considers the units' appropriateness for performing both application. We
      based our conclusions on a unit's performance and humans factor design, as
      determined by our testing, and on its five-year life-cycle cost, as determined by
      our net present value (NPV) analysis. While we rated all evaluated units
      acceptable for each appropriate category, we did identify some significant
      differences that enabled us to rank the units in order of preference. We have
      included a Selection, Purchasing, and use guide at the end of this study to help
      facilities identify the unit that will best meet their needs.

PMID- 9283921
TI  - Pre-1993 HAMO LS-76 instrument washers without thermal protection can overheat.

PMID- 9283922
TI  - Observations on the brains of demented old people. B.E. Tomlinson, G. Blessed and
      M. Roth, Journal of the Neurological Sciences (1970) 11, 205-242 and Observations
      on the brains of non-demented old people. B.E. Tomlinson, G. Blessed and M. Roth,
      Journal of Neurological Sciences (1968) 7, 331-356.

PMID- 9283923
TI  - The treatment of stupor associated with MRI evidence of cerebrovascular disease.
AB  - OBJECTIVE: To describe the treatment and outcome of organic stupor associated
      with MRI evidence of cerebrovascular disease. DESIGN: A case series of three
      patients. SETTING: An urban mental health of the elderly service in southeast
      London. PATIENTS: Aged 69 years, 72 years and 78 years. Two had organic catatonic
      disorder and the third organic depressive disorder. INTERVENTIONS: Diazepam,
      carbamazepine, antidepressants or electroconvulsive therapy (ECT). MAIN OUTCOME
      MEASURES: Resolution of symptoms and discharge from hospital. RESULTS: Symptoms
      resolved between 1 and 10 days. All patients were able to return home but
      relapsed over the following 12 months. One relapse occurred when a patient
      stopped diazepam and moclobemide. CONCLUSIONS: It is proposed that the initial
      treatment of organic stupor associated with cerebrovascular disease should
      include a benzodiazepine or carbamazepine. If patients fail to respond then ECT
      should be considered. The safety of ECT is not known, when treating patients with
      depressive disorder associated with cerebrovascular disease.

PMID- 9283924
TI  - The practice of geriatric psychiatry in three countries: observations of an
      American in the British Isles.
AB  - The author compares the practice of geriatric psychiatry among three countries:
      Ireland, the United Kingdom and the United States. The two main areas reviewed
      are how the practice of geriatric psychiatry is done, and the mental health
      services available in each country, including organizational characteristics. The
      US is the most entrepreneurial of the three, Britain's greatest strength is the
      uniformity and comprehensiveness of its services, and Ireland provides an
      excellent model for nations of comparable size. Considerable change is occurring
      in all three countries.

PMID- 9283925
TI  - Screening of dementia in community-dwelling elderly through informant report.
AB  - Screening tools for cognitive decline still have low accuracy for dementia,
      mainly in cases of mild dementia. All of them are affected by factors such as
      age, sex, educational level, sensory deficits and several mental disorders. The
      information provided by a proxy close to the patient has been used during recent
      years in dementia diagnosis. Therefore, new questionnaires, which use
      standardized information from relatives, have been developed. The aim of this
      study was to validate a Spanish version (S-IQCODE) of the Informant Questionnaire
      on Cognitive Decline in the Elderly (IQCODE), a dementia screening questionnaire
      in Spanish population-based samples. A validity study of the screening tool was
      carried out in two population-based samples of community-dwelling elderly with
      different sociodemographic characteristics (urban and rural samples). Dementia
      diagnosis was performed by neurologists according to DSM-III-R criteria. The S
      IQCODE showed a higher accuracy than the MMSE in both samples: sensitivity of 82%
      and 83% vs 73% and 83%, specificity of 90% and 83% vs 78% and 74%, accuracy of
      89% and 83% vs 77% and 75%. Moreover, while the S-IQCODE did not have
      associations with any extraneous factors, the MMSE showed significant
      correlations with age (-0.51), educational level (0.62), mental health (-0.40),
      premorbid intelligence (0.67) and intellectual level (0.75). The results obtained
      with the S-IQCODE show that it could possibly be applied in screening for
      dementia in community-dwelling elderly.

PMID- 9283926
TI  - Placebo-controlled treatment trial of depression in elderly physically ill
      patients.
AB  - OBJECTIVES: To determine the response of physically ill elderly depressed
      patients to treatment. DESIGN: Acute geriatric medical inpatients with
      depression, randomly assigned to an 8-week double-blind placebo-controlled trial
      of fluoxetine. MAIN OUTCOME MEASURE: Response rate as defined by the 17-item
      Hamilton Depression Rating Scale. RESULTS: Eighty-two patients entered the trial;
      62 patients (all those who had completed at least 3 weeks of treatment) were
      included in the efficacy analysis. Forty-two completed the full 8 weeks (21 in
      each group) with response rates of 67% in the fluoxetine group and 38% in the
      placebo group. No significant difference was found between the responses of the
      two groups (p = 0.12). There was a trend for results in the fluoxetine group to
      continue to improve with time. On secondary analysis those patients with serious
      physical illness who completed 5 or more weeks (N = 37) showed a significant
      improvement in mood if treated with fluoxetine (p = 0.02). CONCLUSIONS: The main
      benefit of antidepressants is to approximately double the chances of recovery.
      This trial showed the response rate of the fluoxetine treated group was increased
      by a factor of 1.8 over the placebo group in an 8-week period. The presence of
      physical illness, often severe and/or multiple, did not reduce the effectiveness
      of the medication, which was well tolerated overall. Those with serious physical
      disease responded significantly better to drug treatment; this will require
      further work. Psychological support was also considered to be important.

PMID- 9283927
TI  - Alcohol abuse: a source of reversible functional disability among residents of a
      VA nursing home.
AB  - The prevalence of psychiatric disorders was determined in a sample of 196 VA
      nursing home residents who were interviewed using the modified Schedule for
      Affective Disorders and Schizophrenia (mSADS). Of the 160 subjects for whom data
      were available, 86% had a diagnosis of at least one psychiatric disorder. The
      prevalence of clinically significant cognitive impairment was 60.6% and of major
      depression 13.8%. Of 110 residents for whom alcohol histories were obtained, 32
      (29%) had a lifetime diagnosis of alcohol abuse. The degree of impairment in
      activities of daily living improved significantly from the time of admission to
      the time of the evaluation (average 1.4 years) among those who were recently
      abusing alcohol compared to those who formerly abused alcohol and those who never
      abused alcohol. The effect is clinically as well as statistically significant and
      has the potential benefit of reducing caregiver burden and health care costs for
      the elderly.

PMID- 9283928
TI  - Neuroleptic prescribing to the community elderly in Nottingham.
AB  - DESIGN: A cross-sectional pilot survey of computerized prescribing databases and
      written general practitioner records. Data were abstracted by the first author
      using a standard proforma. SETTING: Six out of 12 general practices situated in
      an area of north Nottingham known to have a high density of residential and
      nursing homes cooperated with the exercise (one was excluded because it lacked a
      computer system, one because the principal had a specialist commitment to old age
      psychiatry and four were self-excluded). PATIENTS: Patients recorded as receiving
      repeat prescriptions of oral preparations of thioridazine, chlorpromazine,
      promazine, haloperidol or trifluoperazine. MEASURES: Point prevalence rates of
      neuroleptic repeat prescribing classed by age group and, in the case of the
      elderly, residential status. For elderly recipients: median (range) duration on
      neuroleptics, median (range) time since last review and numbers (percentages)
      having various characteristics. RESULTS: Elderly patients were found to be more
      likely consumers of neuroleptic medication than their younger counterparts. If
      these results are extrapolated nationwide, then approximately half the patients
      receiving repeat prescriptions for the commonest oral neuroleptics emerge as
      elderly and of these about half are in nursing/residential care. Patients in
      nursing/residential homes suffering dementia formed the largest group of
      recipients, but have the least monitoring by psychiatric teams. CONCLUSION: The
      result highlight a need for a close partnership between primary care, community
      care facilities and old age psychiatric teams to ensure adequate monitoring and
      the implementation of psychological strategies to minimize their use.

PMID- 9283929
TI  - Partnership nursing home care for dementia: the Glasgow experience--one-year
      follow-up.
AB  - The outcome of the transfer of 60 elderly patients suffering from dementia from
      hospital to nursing home care under a partnership contract was reviewed at 6 and
      12 months following transfer. The nursing home population had fared badly
      compared with patients remaining in hospital during the first 3 months. This
      difference was less evident at 6 months follow-up and had disappeared at 12
      months follow-up. It seems that a partnership agreement such as this can deliver
      a quality of health care at least as good as hospital treatment as long the
      transfer is handled carefully.

PMID- 9283930
TI  - Costs of dementia and dementia care: a review.
AB  - Costs of dementia care constitute a great part of the total costs of care for
      elderly. Because the prevalence of dementia is linked to increasing age, and the
      number of the oldest old is rising, the costs of dementia care will increase
      considerably in the forthcoming decades. In this review, research describing
      costs of dementia care has been analysed and classified. The available database
      in this field is small, though expanding, and the methodological problems are
      obvious. Differences between countries, and between different periods of time,
      are difficult to analyse due to different methods of financing and organizing
      care. The main result of the present study is that the costs of dementia care
      differ considerably in the literature. One important reason for this variability
      is that the number of included cost categories vary, leading to a wide range of
      costs. Unpaid informal care forms a major part of the total costs, but the theory
      of costing informal care is complicated.

PMID- 9283931
TI  - Cost of illness due to dementia in Sweden.
AB  - The gross cost of illness due to dementia was estimated to be SEK30.7 billion in
      1991 while the net cost was estimated to be SEK20 billion. The sensitivity
      analysis showed a variation between SEK20 billion and SEK36 billion in 1991.

PMID- 9283932
TI  - Media triggers of post-traumatic stress disorder 50 years after the Second World
      War.
AB  - Post-traumatic stress disorder (PTSD) may present many years after the original
      trauma. Case studies of two elderly patients are described. Both had experienced
      life-threatening combat situations and witnessed intense suffering during the
      Second World War. Marked distress was triggered by the media commemorating the
      fiftieth anniversary of the end of the war. PTSD patients often avoid talking of
      their traumatic experiences because of associated distress. Without taking a
      military and trauma history from elderly patients the diagnosis is likely to be
      missed.

PMID- 9283933
TI  - Neuropathy associated with tricyclic antidepressants.

PMID- 9283934
TI  - Counseling sexually active teenagers treated with potential human teratogens.
AB  - Adolescents with hemoglobinopathies need daily chelation therapy with drugs which
      are known or suspected to be teratogenic. The prevention of fetal exposure to
      such drugs is therefore a major task for health professionals caring for these
      patients. We describe a pilot program aiming to prevent pregnancy among sexually
      active adolescents treated with iron chelators in Toronto. Most of them had
      normal response to GnRH, suggesting endocrinologic fertility, and unlike the
      literature concerning their healthy peers, all sexually active patients in this
      study reported use of at least one form of contraception.

PMID- 9283936
TI  - Programs and services to prevent pregnancy, childbearing, and poor birth outcomes
      among adolescents in rural areas of the southeastern United States.
AB  - PURPOSE: To illustrate how rural adolescents' needs for pregnancy prevention and
      improved birth outcomes are currently being addressed, and to suggest strategies
      for future programs. METHODS: Local and state-level informants knowledgeable
      about services to adolescents in the Southeastern United States were identified.
      Semistructured interviews were used to determine the program start date and time
      frame, funding sources, target population, participating counties, implementing
      agency or organization, specific program services, and status of program
      activities. These programs were categorized by the type of services offered and
      the population targeted. RESULTS: The most common adolescent services in the
      rural Southeast attempt either to improve life options of youth, reduce sexual
      activity, or provide prenatal and postnatal care. Unlike urban areas where there
      are a variety of family planning providers, in the rural Southeast, health
      departments are the primary source of family planning for adolescents. There are
      no abortion providers in most rural areas of the Southeast. The majority of rural
      programs that include adolescents among the population served are developed for
      all women rather than specifically for adolescents. Programs specific to rural
      adolescents are described. CONCLUSIONS: The majority of programs in the rural
      Southeast address only selected adolescent health issues. Successful
      interventions require locally supported, multipronged, intensive approaches with
      consistent messages targeted to high-risk populations. Evaluation tools are
      needed to determine the effectiveness of each component of prevention programs.

PMID- 9283935
TI  - Female adolescents and onset of sexual intercourse: a theory-based review of
      research from 1984 to 1994.
AB  - PURPOSE: To review a decade of research on the correlates of early onset of
      sexual intercourse among female adolescents in the United States, using Social
      Cognitive Theory as a framework for classification. METHODS: Forty-nine studies
      published in peer-reviewed journals between 1984 and 1994 were reviewed and their
      findings coded by two independent coders. RESULTS: Findings indicate that most of
      the studies emphasized quantitative methodologies, using cross-sectional designs
      and univariate statistical analyses. Many studies lacked a theoretical framework
      or conceptual model to guide their investigations. When evaluating empirical
      findings, 61% of the studies found environmental correlates and 47% found
      biological factors (e.g., age and pubertal development) to be significantly
      associated with early initiation of sexual intercourse. CONCLUSION: These
      findings raise important questions about the quality of research on adolescent
      sexuality, as well as its relationship to the development of risk-reduction
      programs which tend to focus mainly on intrapersonal factors (such as attitudes,
      knowledge, and expectancies.

PMID- 9283937
TI  - Social factors predicting postpartum choice of Norplant among African-American
      and non-Hispanic white adolescents.
AB  - PURPOSE: This study was designed to determine the factors associated with
      Norplant choice for postpartum teens. METHODS: A total of 151 teenagers, ages 12
      20 years, who delivered at the Medical Center of Delaware from July to December
      1992, were offered insertion of Norplant within 48 h postpartum. A structured
      interview was conducted in the postpartum period after nondirective counseling
      sessions including a physical demonstration using anatomical models of various
      contraceptive methods. Student's t-tests, chi-square, and multivariate analyses
      were used. RESULTS: Eighty-six teenagers were African-American (mean age = 17.3
      +/- 1.9 years) and 65 non-Hispanic white (NHW) (mean age = 18.3 +/- 1.5 years).
      The NHW teenagers were older (p < 0.001); the African-American teenagers were
      more likely to have Medicaid (49% vs. 14%; p < 0.001) and to have one or more
      friends who use Norplant (62% vs. 34%; p < 0.001). In multivariate analyses, NHW
      teenagers were more likely to choose Norplant if they had discussed their choice
      with a parent or guardian [adjusted odds ratio (AOR) = 14.6, 95% confidence
      interval (CI), 2.12-100.57]; had Medicaid funding (AOR = 12.1; 95% (CI), 10.6
      91.34); and had any friends who used Norplant (AOR = 6.3; 95% (CI), 1.38-28.40).
      However, for African-American teenagers, the strongest predictor for choice of
      Norplant was number of prior children delivered. After two deliveries, there was
      a better than four-fold likelihood (AOR = 4.8; 95% (CI), 1.47-15.94) that African
      American teenagers would choose Norplant. For the African-American teenagers,
      parental discussion, Medicaid status, and friends' use of Norplant were not as
      important as family size, but far greater percentages of the African-American
      teenagers had access to Medicaid funding and peers who used Norplant.
      CONCLUSIONS: NHW and African-American teenagers choose Norplant for different
      reasons. Lack of funding may have been a barrier to choosing Norplant.
      Discussions with parents and friends have a positive influence on choosing
      Norplant for NHW teenagers. African-American teenagers were more likely than NHW
      to have Medicaid coverage, and more frequently choose Norplant if the current
      birth was their third child.

PMID- 9283938
TI  - Aggression and environmental risk among low-income African-American youth.
AB  - PURPOSE: This study examined the extent to which individual, family, and
      environmental factors discriminated between aggressive and nonaggressive African
      American youth. METHODS: One hundred fifty African-American boys and girls from
      eight housing communities in a medium sized Alabama central city were surveyed.
      From this nonrandom sample, information was collected concerning respondents'
      demographics, family characteristics, exposure(s) to violence, questions
      pertaining to weapon possession, and a peer-nominated question on aggression.
      Multivariate analysis was employed to differentiate aggressive from nonaggressive
      youth. RESULTS: Discriminant function analysis found gender (males) and age
      (older) to be important discriminators between nonaggressive and aggressive
      youth. In addition, a significant amount of separation between these groups was
      accounted for by their varying degrees of exposure to violence, specifically as a
      witness to and victim of violence, and their possession of a weapon. CONCLUSIONS:
      Findings provide evidence that victimization and witnessing violence were
      significantly related to aggressive behavior among this sample of African
      American youth. In addition, this study confirms the clinical significance of
      environment and its potential role in predicting physical health, mental health,
      and social and behavioral outcomes for youth.

PMID- 9283939
TI  - Transdermal versus oral administration of estrogen in the management of lumbar
      spine osteopenia in an adolescent with anorexia nervosa.

PMID- 9283940
TI  - Mondor disease: an unusual consideration in a young woman with a breast mass.

PMID- 9283941
TI  - Associations between lifestyle and cardiovascular risk factors in 18-year-old
      Australians.
AB  - PURPOSE: This study aimed to examine associations between cardiovascular risk
      factors and variables reflecting health-related behaviors in 18-year-old
      Australians. METHODS: Anthropometry, blood pressure, nonfasting serum
      cholesterol, and physical fitness were measured in 301 male and 286 female
      Australian 18-year-olds. Usual physical activity, smoking, and drinking habits
      were assessed by questionnaire. RESULTS: Systolic (SBP), with mean SBP higher by
      14 mm Hg in males, related positively to weight for height for age and "unsafe"
      drinking (exceeding Australian national guidelines) and negatively to fitness and
      birth weight. Total cholesterol, which was positively associated with waist-hip
      ratio and negatively with fitness, was higher in females [mean 4.4 mmol/L, 95%
      confidence interval (CI) 4.3, 4.5] than in males (mean 4.1 mmol/L, 95% CI 4.0,
      4.2). In 24% of males and 48% of females, usual levels of physical activity were
      low, consistent with lower scores on fitness tests in females. Thirty percent of
      males and 24% of females regularly drank at "unsafe," levels while 26% of males
      and 29% of females smoked. Smoking was associated with "unsafe" drinking.
      CONCLUSION: Cardiovascular risk factors in 18-year-olds are related to smoking,
      "unsafe" drinking, and physical inactivity, particularly in females. These
      behaviors should be targeted in designing multimodal health promotion programs
      appropriate for these young adults.

PMID- 9283942
TI  - Presidential address.

PMID- 9283943
TI  - Clinical preventive services for adolescents: position paper of the Society for
      Adolescent Medicine.

PMID- 9283944
TI  - Molecular aspects of steroid hormone action in the male reproductive axis.
AB  - Both T and E play important roles in the regulation of reproductive function at
      the cellular and tissue levels in males. In addition to a causal role in the
      development of the male reproductive phenotype, androgens provide feedback
      regulation to the hypothalamus and to the pituitary in humans. Estrogen action is
      critical for normal bone fusion and mineralization in both men and women, and E
      action appears to play an important role in hypothalamic suppression of
      gonadotropin levels.

PMID- 9283945
TI  - Neurological testing in erectile dysfunction.

PMID- 9283946
TI  - Pharmacokinetics of 7 alpha-methyl-19-nortestosterone in men and cynomolgus
      monkeys.
AB  - Testosterone and its esters are widely used for androgen replacement therapy. In
      the prostate, testosterone ins 5 alpha-reduced to dihydrotestosterone (DHT),
      which leads to an amplification of its stimulatory activity in this and other
      tissues that have significant 5 alpha-reductase activity. While this
      amplification is essential during fetal development, it has potentially
      undesirable consequences during adult life. 7 alpha-Methyl-19-nortestosterone
      (MENT) is a potent synthetic androgen that does not undergo 5 alpha reduction and
      is therefore being investigated for long-term clinical use because it is expected
      to be less stimulatory to the prostate. Since we anticipate using MENT acetate
      (MENT Ac) rather than MENT as the form of this androgen in humans, the
      bioavailability of MENT following the administration of MENT and MENT Ac was
      investigated in cynomolgus monkeys. Equimolar concentrations of MENT or MENT Ac
      were administered as a continuous subcutaneous infusion via Alzet osmotic pumps.
      Serum MENT levels were measured by radioimmunoassay (RIA) in blood samples
      collected daily for 4 days during steady state. The serum MENT levels were not
      significantly different in the two groups (11.3 +/- 1.6 vs. 13.1 +/- 1.2 nmol/L).
      This suggested that MENT Ac was rapidly converted to MENT in circulation. The
      hydrolysis of MENT Ac to MENT was confirmed by the in vitro incubation of MENT Ac
      with blood or plasma and the demonstration of MENT in products following
      separation by high-performance liquid chromatography (HPLC). Following the
      demonstration of the safety of MENT Ac in subchronic toxicity studies in rats and
      rabbits, a pharmacokinetic study was performed in men. In normal men, a single
      intravenous bolus of 500 micrograms of MENT led to peak serum MENT levels at 3
      minutes after dosing (when the first samples were collected), followed by an
      exponential decline, reaching undetectable levels by 180 minutes. The average
      terminal half-life and the metabolic clearance rate (MCR) were calculated to be
      40 minutes and 2,360 L/day, respectively. The results of the pharmacokinetic
      studies show that in both men and monkeys, the MCR of MENT is much faster than
      the values reported for testosterone. The faster MCR can be attributed, in part,
      to the finding that, in contrast to testosterone, MENT showed no binding to sex
      hormone binding globulin (SHBG).

PMID- 9283947
TI  - In the male brown-Norway (BN) male rat, reproductive aging is associated with
      decreased LH-pulse amplitude and area.
AB  - The Brown-Norway (BN) rat has been proposed as a rodent model for the study of
      human male reproductive aging. As in man, reduction in serum or plasma
      testosterone (T) and both testicular (primary) and hypothalamic-pituitary
      (secondary) reproductive dysfunction have been associated with aging in male BN
      rats. However, the presence of secondary testicular failure in this rodent, as
      indicated by low serum luteinizing hormone (LH) levels, needs further
      corroboration. The present study was designed to determine whether age-related
      differences in the pulsatile patterns of pituitary LH and follicle-stimulating
      hormone (FSH) secretion occur in gonad-intact male BN rats. Three age groups were
      examined: young (3-4 months), middle aged (12-13 months), and old (21-22 months).
      Using intra-atrial cannulae, serial 5-minute blood samples were withdrawn from
      conscious, unrestrained animals. Plasma LH concentrations were determined by a
      supersensitive immunofluorometric assay (FIA) and FSH and T by radioimmunoassay
      (RIA). Mean T levels were different among groups (young > middle age > old). In
      young rats, T levels were higher in the late morning/early afternoon than in the
      late afternoon: this variation was not found in older rats. Mean FSH
      concentrations were higher in the old than in the middle-aged and young rats.
      Significant differences in mean LH levels were not found among groups. Compared
      to young rats, shortened pulse interval and reduced area of pulses characterized
      the secretory pattern of both gonadotropins in old rats. In addition, LH-pulse
      amplitude and total area of LH pulses were also significantly lower in old than
      in young rats. Besides the well-recognized primary testicular failure that occurs
      in the old BN rat, this study confirms a hypothalamic-pituitary deficiency that
      makes this rodent model ideal for studying human male reproductive aging.

PMID- 9283948
TI  - Comparison between testosterone enanthate-induced azoospermia and oligozoospermia
      in a male contraceptive study. V. Localization of higher 5 alpha-reductase
      activity to the reproductive tract in oligozoospermic men administered
      supraphysiological doses of testosterone.
AB  - Sex steroid contraceptive regimes result in incomplete suppression of
      spermatogenesis in 30-45% of Caucasian men. The basis for this is unclear, but
      differences in the activity of 5 alpha-reductase (5 alpha R) have been
      demonstrated. Two isoforms of 5 alpha R have been described: 5 alpha R1 is found
      in skin, whereas the predominant from in reproductive tissues is 5 alpha R2. To
      investigate possible contributions of these isoenzymes, we have investigated
      androgen-dependent changes in seminal plasma androgens (5 alpha R2) and sebum
      production (5 alpha 1) during administration of a supraphysiological dose (200 mg
      IM weekly) of testosterone enanthate (TE) to 33 normal men. Eighteen men rapidly
      (< 20 weeks treatment) became azoospermic, the remainder having a mean sperm
      density of 2.0 +/- 0.6 x 10(6) at that time. The concentrations of testosterone
      and 3 alpha, 17 beta-androstanediol glucuronide (AdiolG) were lower in seminal
      plasma than in blood but rose by a similar degree (100%) after 16 weeks TE
      treatment in both groups. There were no differences in seminal-plasma
      concentration of testosterone or AdiolG between azoospermic and oligozoospermic
      responders, either pretreatment or after 16 weeks TE treatment. Although the
      concentrations of dihydrotestosterone (DHT) were similar in seminal plasma and
      blood pre- and posttreatment, there was a selective increase in seminal plasma
      DHT concentration in the oligozoospermic responders from 2.12 +/- 0.29 to 2.94 +/
      0.33 nmol/L (P < 0.05), while there was no significant change in the azoospermic
      responders (2.18 +/- 0.31-2.54 +/- 0.27 nmol/L) after 16 weeks of TE treatment.
      Dihydrotestosterone in seminal plasma is primarily derived from 5 alpha R
      activity in the epididymis. The concentration of prostaglandin E2 (PGE2) in
      seminal plasma was unchanged during TE treatment. Sebum excretion was increased
      during TE treatment, but there were no difference between azoospermic and
      oligozoospermic responders pretreatment or after 16 weeks TE treatment. These
      results are consistent with the hypothesis that incomplete suppression of
      spermatogenesis during TE treatment is associated with a relatively higher 5
      alpha R activity in the reproductive tract (epididymis and/or testis) during TE
      treatment. As the predominant form of 5 alpha R in the reproductive tract is 5
      alpha R2 (type 2), we conclude that the increase in activity derives from this
      form of the enzyme, rather than the type 1 form (5 alpha R1) predominantly found
      in nongenital skin.

PMID- 9283949
TI  - Differential methylation in steroid 5 alpha-reductase isozyme genes in
      epididymis, testis, and liver of the adult rat.
AB  - DNA methylation has been largely involved in the regulation of tissue-specific
      gene expression. The aim of the study was to determine the methylation pattern of
      steroid 5 alpha-reductase genes 1 and 2 in two reproductive tissues (testis and
      epididymis) and a nonreproductive tissue (liver) that exhibit different contents
      of steroid 5 alpha-reductase isozymes. These isozymes induce the bioconversion of
      testosterone to dihydrotestosterone that in mammals is a key molecule for
      external genitalia development. Genomic DNA from the testis, the epididymis, and
      the liver from normal adult rats was used to determine cytosine and adenine
      methylation pattern of steroid 5 alpha-reductase genes 1 and 2 by restriction
      fragment length polymorphism (RFLP) analysis using restriction enzymes sensitive
      to adenine (Mbo I and Sau3A I) and cytosine (Hpa II and MSP I) methylation. We
      also evaluated the expression of both steroid 5 alpha-reductase genes by northern
      blot. When genomic DNA was digested with Hpa II or Msp I, we found that steroid 5
      alpha-reductase gene 2 was less cytosine methylated in the epididymis and in the
      testis than in the liver. In contrast, when genomic DNA was digested with Mbo I
      or Sau3A I, we observed that gene 2 was more adenine methylated in the epididymis
      and in the testis than in the liver. 5 alpha-Reductase gene 1 presented the same
      adenine- and cytosine-methylation pattern in the studied tissues. We also found a
      differential expression of steroid 5 alpha-reductase genes. Gene 2 was expressed
      both in the testis and the epididymis but not in the liver; whereas gene 1 was
      only expressed in the latter. Our results suggest that the differential
      methylation pattern in 5 alpha-reductase gene 2 in reproductive and
      nonreproductive tissues should be involved in the regulation of its expression.

PMID- 9283950
TI  - Estrogen receptors are present in the epididymis of the rooster.
AB  - Our recent discovery that testicular germ cells and epididymal sperm contain
      active P450 aromatase suggests that the reproductive tract may be a target for
      estrogen. Therefore, the objective of this study was to determine if estrogen
      receptors (ER) are present in the avian epididymis using immunocytochemistry,
      northern blot analysis, and in situ hybridization. Immunoperoxidase staining for
      ER was found principally in nuclei of nonciliated epithelial cells of proximal
      and distal efferent ductules and the epididymis duct. The ciliated cells also
      appeared to be slightly positive in the efferent ductules. Week immunostaining
      was also observed in the connective tissue of the epididymis duct. Immunostaining
      was more intense in epithelial cells of the efferent ductules than in epithelial
      cells of the epididymal duct of connective tissue cells. Strong specific
      hybridization signals for ER mRNA corresponded to the same areas exhibiting
      immunocytochemical localization. The presence of ER mRNA in the epididymis was
      confirmed by northern blot analysis, which showed a single band corresponding to
      approximately 7.8 kb, similar to that found in chicken oviduct. Based on these
      data, we suggest that the efferent ducts of the rooster are a primary target for
      estrogen and that estrogen may have a role in the regulation of avian epididymal
      function.

PMID- 9283951
TI  - Localization and effects of calcitonin gene-related peptide in the testicular
      vasculature of the rat.
AB  - Using laser Doppler flowmetry, the effects of unilateral intratesticular
      injection of calcitonin gene-related peptide (CGRP) and CGRP8-37, a CGRP-receptor
      antagonist, on right- and left-testicular blood flow and mean arterial pressure
      were studied on anesthetized adult rats. Calcitonin gene-related peptide in doses
      of 5 and 50 ng increased blood flow 37 +/- 11% (mean +/- SEM, P < 0.05) and 30 +/
      5% at 5 mm, but not 15 mm, away from the injection site, respectively. They did
      not influence mean arterial pressure nor blood flow in the contralateral testis.
      Five-hundred nanogram doses increased testicular blood flow in the injected
      testis at a point 15 mm away from the injection site (22 +/- 3%, P < 0.05) and
      caused a slight decrease in mean arterial pressure (-12 +/- 3%, P < 0.05). The
      highest dose, 5 micrograms, caused a large (-39 +/- 3%, P < 0.05) fall in mean
      arterial pressure within 1 minute after injection, and testicular blood flow was
      reduced in both the injected (-9 +/- 2%, P < 0.05, 15 mm away from injection
      site) and contralateral testis (-20 +/- 5%, P < 0.05). Pretreatment with 500 ng
      of the receptor antagonist, CGRP8-37, did not significantly attenuate the blood
      flow increasing affect of 50 ng CGRP, nor did 50 micrograms CGRP 8-37 (given
      alone) influence basal testicular blood flow in the injected testis. Using
      Immunohistochemistry, CGRP-containing nerves were observed in the superior and
      interior spermatic nerves, in the testicular artery, and in the veins leaving the
      testis but not in intratesticular blood vessels. CONCLUSIONS: 1) CGRP is a potent
      vasodilator in the testicular vasculature and it may be involved in the local
      regulation of testicular blood flow: 2) the testis has limited capacity to
      autoregulate and is consequently unable to maintain a constant testicular blood
      flow during large and rapid reductions in blood pressure, and 3) the local and
      systemic effects of vasodilators act in opposite directions in the testis.

PMID- 9283952
TI  - Development and characterization of a prepubertal rat Sertoli cell line, 93RS2.
AB  - Sertoli cells in the seminiferous epithelium provide both structural and
      nutritional support to germ cells during spermatogenesis. Primary Sertoli cells
      in culture are an effective tool for the in vitro study of Sertoli cell function;
      however, primary cultures are inherently variable, time consuming to prepare,
      expensive, and wasteful of animals. We therefore developed a Sertoli cell line,
      called 93RS2, by immortalizing primary Sertoli cells derived from prepubertal
      rats with SV40 tsA255. This cell line proliferates at the permissive temperature
      (32 degrees C) and has enhanced expression of a differentiated Sertoli cell
      phenotype at the nonpermissive temperature (40-41 degrees C). Cytogenetic
      analysis demonstrated that 93RS2 has 42 chromosomes per cell, the same as a
      normal rat. mRNA analysis showed that this cell line, when cultured at a
      nonpermissive temperature, exhibited increased expression of transferrin in the
      presence of testosterone and enhanced expression of sulfated glycoprotein-2. A
      tumorigenicity assay showed that 93RS2 cells were temperature-dependent for
      growth in soft agar and were capable of forming tumors in nude mice. In
      conclusion, this rat 93RS2 cell line should be useful for the study of Sertoli
      cell function.

PMID- 9283953
TI  - Low density lipoprotein receptor-related protein-1 expression in the testis:
      regulated expression in Sertoli cells.
AB  - The low density lipoprotein receptor-related protein (LRP-1) is a multiligand
      receptor capable of mediating endocytosis of a wide array of ligands that relate
      to both lipoprotein metabolism and proteinase regulation. Many of its ligands are
      proteinases, proteinase-inhibitor complexes, and lipoproteins known to be
      contained within the luminal fluid of the seminiferous tubules or in the
      interstitial spaces of the testis. Immunocytochemical analysis was performed to
      characterize the pattern of expression of LRP-1 in cells of the rat testis.
      Immunoperoxidase staining localized LRP-1 to the cytoplasm of Sertoli cells. The
      distribution and intensity of the Sertoli cell staining was found to vary
      according to the stages of the cycle of the seminiferous epithelium. Staining was
      weak in the basal cytoplasm of Sertoli cells during stages II-VIII and strong and
      granular in the supranuclear cytoplasm during stages XII-XIV and stage I of the
      cycle. Immunogold labeling showed gold particles associated with the basal and
      adluminal plasma membranes, with endocytic vesicles, and with endosome membranes.
      Labeling was also observed on the plasma membrane and membranes of the endocytic
      apparatus in macrophages and Leydig cells in the interstitial space. Infusion of
      125I-Labeled LRP-1 antibody into seminiferous tubules followed by radioautography
      showed silver grains overlaying the ad-luminal plasma membrane of Sertoli cells
      at time 0 and in endocytic vesicles and endosomes in the supranuclear region of
      Sertoli cells 10-minutes postinjection. When the 125I-Labeled LRP-1 antibody was
      injected into the interstitial space, silver grains overlayed the basal plasma
      membrane and coated endocytic pits of Sertoli cells at time 0 and, at 10 minutes,
      the grains labeled endosomes located in the basal pole of Sertoli cells. 125I
      Labeled LRP-1 antibody also labeled the plasma membrane and the endocytic
      apparatus of macrophages and Leydig cells. The absence of immunogold labeling and
      radioautographic silver grains within lysosomes of Sertoli cells, Leydig cells,
      and macrophages suggests that internalized LRP-1 is recycled back to the cell
      surface. The presence of LRP-1 in the endocytic compartment of these cells is
      consistent with its functioning in the clearance of proteases involved in
      seminiferous tubule remodeling and/ or the uptake of cholesterol-bound
      lipoproteins necessary for the biosynthesis of testosterone. In conclusion, the
      results of these studies demonstrated for the first time the presence of LRP-1
      receptor in the endocytic compartments of Sertoli cells and interstitial cells of
      the rat testis.

PMID- 9283954
TI  - HCG binding to the testicular LH receptor is similar in fertile, subfertile, and
      infertile stallions.
AB  - Recent evidence in our laboratory suggests that the cause of idiopathic
      subfertility/infertility in breeding stallions may originate in the testes at the
      luteinizing hormone (LH) receptor or postreceptor level. The objective of this
      research was to determine if LH receptor binding activity is altered in
      subfertile and infertile stallions. Six fertile, three subfertile, and three
      infertile stallions, ages 11-23 years, were classified according to normal semen
      parameters and pregnancy rates and then castrated in the breeding season. Blood
      was collected prior to castration, and plasma was stored until analyzed for LH,
      follicle stimulating hormone (FSH), estrogen conjugates (EC), estradiol (E2),
      testosterone (T), and inhibin (I) by radioimmunoassay (RIA). Testicular cell
      membranes were prepared and snap-frozen until analyzed for LH binding activity by
      radioreceptorassay (RRA) using increasing amounts of I125 human chorionic
      gonadotropin (hCG). Luteinizing hormone receptor numbers and affinity constants
      were determined by Scatchard analysis. Plasma LH, FSH, EC, E2, and T levels did
      not differ between fertile and subfertile stallions, but LH and FSH were
      significantly higher (P < 0.05) and EC, E2, T, and I levels were significantly
      lower (P < 0.05) in infertile stallions as compared to fertile and subfertile
      stallions. Receptor number (Rt) and affinity constants Ka were similar (P > 0.05)
      between fertile (Rt = 9.44 x 10(-11) M, Ka = 0.300 x 10(10) M-1), subfertile (Rt
      = 13.02 x 10(-11) M, Ka = 0.194 x 10(10) M-1), and infertile (Rt = 7.65 x 10(-11)
      M, Ka = 0.380 x 10(10) M-1) stallions. In conclusion, these data suggest that an
      endocrine dysfunction in the testes of stallions with poor fertility may not be
      due to a LH receptor disorder but may be due to a postreceptor malfunction.

PMID- 9283955
TI  - The effects of gonadotropin-releasing hormone immunization and recombinant
      follicle-stimulating hormone on the Leydig cell and macrophage populations of the
      adult rat testis.
AB  - The objective of this study was to investigate the role of the gonadotropins and,
      in particular follicle-stimulating hormone (FSH) in maintaining the Leydig cell
      and macrophage populations of the adult rat testis. Adult male Sprague-Dawley
      rats received a gonadotropin-releasing hormone (GnRH) immunogen for a period of
      12 weeks in order to induce a selective deficiency in luteinizing hormone (LH)
      and FSH. Recombinant human FSH was then administered for 7, 14 and 21 days and
      macrophages and Leydig cells per testis quantified using the "optical disector"
      method. After GnRH immunization, Leydig cell and macrophage numbers were reduced
      by 18% and 68%, respectively, compared with normal controls, resulting in an
      increase in the ratio of Leydig cells to macrophages from 4:1 to 9:1. Leydig
      cells regressed morphologically following GnRH immunization, and macrophage mean
      nuclear diameter was significantly reduced. Administration of FSH did not restore
      the numbers of either cell type; however, FSH did increase macrophage nuclear
      size. Eosinophils and mast cells were also found sparsely scattered throughout
      the interstitium after GnRH immunization and persisted in the FSH-treated
      animals. The results of this study indicate that in the adult rat: 1) both Leydig
      cell and macrophage numbers are reduced in the gonadotropin-deficient testis; 2)
      FSH has no effect on the number of either cell type in the absence of LH; and 3)
      testicular macrophage activity, as indicated by nuclear size, is stimulated by
      FSH, either directly or indirectly.

PMID- 9283956
TI  - Is Leydig cell steroidogenic function affected by the germ cell content of the
      seminiferous tubules?
AB  - The effect of testicular germ cell content on Leydig cell steroidogenic function
      in vivo in adult rats was examined. Three experimental paradigms were used to
      effect germ cell changes. First, a vitamin A-depletion/repletion regimen was used
      to achieve synchrony at different stages of the cycle of the seminiferous
      epithelium and thus produce testes with widely differing germ cell contents.
      Second, long term vitamin A depletion was used to effect germ cell, but not
      Leydig cell, loss. Third, Leydig cells and germ cells first were eliminated from
      the testes of adult rats by the administration of ethane 1,2-dimethane sulfonate
      (EDS) along with testosterone- and estradiol-filled Silastic capsules; Leydig
      cells were then restored to the germ cell-depleted testes by removal of the
      luteiniging hormone (LH)-suppressing capsules. Serum, interstitial fluid, and
      seminiferous tubule fluid testosterone concentrations did not differ between rats
      in which at least 70% of the seminiferous tubules contained germ cells at stages
      VII-VIII or at stages XII-III of the cycle. The capacity of the testes of these
      rats to produce testosterone, assessed by their in vitro perfusion with maximally
      stimulating LH, also showed no differences despite the differences in germ cell
      content. Elimination of germ cells throughout the testes by long term vitamin A
      depletion also did not affect the steroidogenic function of the testes. Finally,
      the steroidogenic function of Leydig cells restored to germ cell-depleted testes
      was indistinguishable from that of germ cell-containing controls. These results,
      taken together, provide evidence supporting the contention that the germ cell
      content of the testis has little or no effect on testicular steroidogenic
      function.

PMID- 9283957
TI  - Antifertility potential of ornidazole analogues in rats.
AB  - In order to determine which part of the ornidazole molecule [1-(3-chloro-2
      hydroxy)propyl-2-methyl-5-nitroimidazole] is responsible for its antifertility
      action, structural analogues were fed to male rats of proven fertility at doses
      equivalent to the antifertility dose of ornidazole (1.82 mmol/kg/day). The
      fertility of the males was tested, before oral gavage (control mating) and after
      10 and 14 days of feeding, by counting the number of fetuses and corpora lutea
      present in females 12 days after mating. The day after the last mating, the
      kinematic parameters of sperm from the cauda epididymidis were assessed
      objectively with a Hamilton-Thorne motility analyzer. Analogues bearing the 2
      nitro and 5-methyl groups on the imidazole ring were inactive if the
      (chlorohydroxy)propyl group were substituted by proton or methyl, hydroxyethyl,
      chloroethyl, or (sulfonylethyl)ethyl groups, indicating that the three-carbon
      side chain of ornidazole was necessary for the antifertility action. Only
      ornidazole and its acetate were effective antifertility agents, but a compound
      bearing the (chlorohydroxy)propyl side chain attached to a nitrogen atom of a
      heterocyclic phthalimide produced a partial but temporary reduction in fertility.
      Similarities of the action of ornidazole with the male antifertility agent, alpha
      chlorohydrin [3-chloro-1,2-propanediol], are discussed.

PMID- 9283958
TI  - The effect of follicle-stimulating hormone therapy on sperm quality: an
      ultrastructural mathematical evaluation.
AB  - We investigated the effect of follicle-stimulating hormone (FSH) administration
      on the ultrastructure of spermatozoa in order to evaluate the potential of FSH
      therapy for improving sperm quality. Forty-six patients exhibiting idiopathic
      oligoasthenoterato-zoospermia who attended the intrauterine insemination (IU), in
      vitro fertilization (IVF), or intracytoplasmic sperm injection (ICSI) program at
      our clinic received FSH in daily dosages of 150 IU over a period of 12 weeks.
      Using transmission electron microscopy, the ultrastructural analysis of
      spermatozoa was performed prior to the start of FSH therapy, after the treatment
      had been finished, and 6 weeks posttherapy. Applying a mathematical formula based
      on submicroscopic characteristics, we calculated the number of morphologically
      normal spermatozoa. After the FSH treatment, the examined subcellular organelles
      achieved a higher percentage of integrity. Follicle-stimulating hormone treatment
      leads to a higher number of morphologically normal spermatozoa. The electron
      microscopic findings indicate that treatment with pure FSH may be an effective
      way to improve sperm quality in cases with oligoasthenoterato-zoospermia.
      Applying the mathematical analysis based on the whole complex of the selected
      sperm characteristics, we obtained a way to evaluate the success of therapy for
      the first time.

PMID- 9283959
TI  - Successful treatment of severe oligozoospermia with sperm washing and
      intrauterine insemination.
AB  - During the period January 1, 1991 through December 31, 1995, 258 patients, in
      whom motile sperm counts for insemination (postwash, processed) were 10.0 million
      motile sperm or less were seen in the andrology unit for sperm washing and
      intrauterine insemination (IUI). No significant female factors were noted on
      history; all female partners had patent Fallopian tubes and were ovulatory
      spontaneously or were treated by the referring gynecologist with clomiphene
      citrate, human menopausal gonadotropin (hMG), or follicle-stimulating hormone
      (FSH) ovulation induction in both anovulatory or ovulatory women. Of the total of
      258 patients, 15 achieved a pregnancy in 284 cycles of IUI in which the
      inseminating motile-count was < 1.0 million motile sperm, resulting in a monthly
      fecundity (f) of 5.3%. The mean (+/-SD) motile count for IUI in this group was
      0.61 (+/-0.29) million sperm, with a range of 0.19-0.95 million motile sperm. The
      initial motile count was 2.97 (3.2) million sperm, with a range of 0.2-12.81
      million sperm. With inseminating motile counts of 1.0-10.0 million motile sperm,
      there were 83 pregnancies after 467 cycles of IUI, resulting in a monthly f of
      17.8%. The mean (+/-SD) motile count for IUI in this group was 4.9 (+/-2.7)
      million motile sperm with a range of 1.0-9.9 million motile sperm. The initial
      sperm count in this group was 10.9 million (+/-7.1), with a range of 1.1-23.7
      million motile sperm. These data suggest that acceptable pregnancy rates can be
      achieved with IUI, even in severely oligozoospermic specimens. Intrauterine
      insemination is less invasive and less costly than other assisted reproductive
      techniques. These data are supportive of IUI prior to attempting other more
      invasive and potentially costly reproductive technologies.

PMID- 9283960
TI  - The impact of reactive oxygen species on bovine sperm fertilizing ability and
      oocyte maturation.
AB  - The objective of this study was to examine the effects of reactive oxygen species
      (ROS) on bovine sperm function and on the developmental competence of in vitro
      matured bovine oocytes. In a first series of experiments, spermatozoa were
      exposed to ROS generated through the use of the hypoxanthine-xanthine oxidase
      system +/- catalase prior to the conduct of in vitro fertilization (IVF).
      Reactive oxygen species exposure reduced significantly (P < 0.001) the rates of
      oocyte penetration (control: 56% +/- 4 SEM; ROS: 16 +/- 2-23% +/- 7 SEM), and
      this effect was reversed by adding catalase (ROS+catalase: 67% +/- 0.3 SEM).
      During IVF, addition of superoxide dismutase (SOD: 1, 10, or 100 U/ml) had no
      effect on penetration rates. However, increasing concentrations of catalase (0.1
      or 1 mg/ml) reduced these rates significantly (control: 70% +/- 3 SEM; treated:
      45% +/- 5 and 1% +/- 1 SEM; P < 0.001). In a second series of experiments, when
      oocytes were matured in vitro in the presence of exogenous antioxidants (SOD: 10,
      100, or 1000 U/ml; beta-mercaptoethanol: 0.01, 0.1, or 0.5 mM; ascorbic acid:
      0.05 mg/ml), the developmental competence of the oocytes after IVF was not
      significantly improved. On the other hand, presumed production of ROS using the
      hypoxanthine-xanthine system at the beginning of the in vitro maturation period
      did improve subsequent developmental competence of the oocytes under some
      conditions and when catalase was present (control: 14% +/- 4 SEM and treated: 23%
      +/- 9 and 27% +/- 8 SEM; P < 0.05). These observations demonstrate that ROS may
      be beneficial to gamete function under specific conditions.

PMID- 9283961
TI  - Premature capacitation of bovine spermatozoa is initiated by cryopreservation.
AB  - Poor motility and abnormal acrosomal morphology only partially explain the
      reduced fertility of cryopreserved bovine spermatozoa. To test the hypothesis
      that cryopreservation procedures (dilution, cooling, freeze-thaw) induce
      capacitation in bovine spermatozoa, two experiments were conducted using semen
      diluted in egg yolk-Tris-glycerol extender (EYTG) (Tris,
      tris(hydroxymethyl)aminomethane). Capacitation was determined prior to and
      following incubation with various concentrations of heparin using the
      chlortetracycline (CTC) fluorescence assay or after preexposure to EYTG using in
      vitro fertilization (IVF) of bovine cumulus-oocyte complexes (COC) in the absence
      of heparin. Fresh ejaculates were divided into four treatments and the first was
      diluted with noncapacitating medium, NCM (+0.3% polyvinyl alcohol (PVA);
      control), then maintained at 23 degrees C for 4 hours. The remaining semen was
      diluted with EYTG; the second treatment was held at 4 degrees C (EYTG-4), and the
      third treatment was held at 23 degrees C (EYTG-23) for 4 hours. The fourth
      treatment was cooled to 4 degrees C over 4 hours, as per the normal industry
      protocol, cryopreserved, and thawed (frozen-thawed). After the 4-hour maintenance
      periods or thawing, all treatments were resuspended either in capacitating medium
      (CM; +0.6% BSA) for the CTC experiment (n = 3) or in NCM for the IVF experiment
      (n = 9-11). Prior to incubation in conditions that support capacitation, the
      percentage of cells exhibiting pattern B (capacitated according to the CTC assay)
      was similar for all treatments with fresh-extended spermatozoa. Immediately
      following the addition of heparin (0, 2, or 10 micrograms/ml), three times more
      frozen-thawed than fresh-extended spermatozoa exhibited pattern B (P < 0.05).
      After 3 or 6 hours of incubation, however, the percentages of cells displaying
      pattern B did not differ among treatments. In the absence of heparin, spermatozoa
      preexposed to EYTG-4 fertilized 2.6x more COC than did control cells (P < 0.001)
      and 9.2x more than spermatozoa preexposed to EYTG but held at 23 degrees C (EYTG
      23; P < 0.0001). No differences were observed among fertilization rates for fresh
      extended (EYTG-4) and frozen-thawed spermatozoa. This study provides evidence
      that premature capacitation occurs in partially (extended and cooled) and fully
      cryopreserved bovine spermatozoa.

PMID- 9283962
TI  - Model experimental system for investigation of heart valve calcification in
      vitro.
AB  - A model system was developed for the in vitro quantitative investigation of the
      calcification process occurring in heart valves. The process of heart valve
      calcification consists of the formation of calcium phosphates at the heart valve
      biological fluid interface. Calcium phosphate deposits may consist of more than
      one calcium phosphate mineral phase, differing with respect to their physical and
      chemical properties. The kinetics of the formation of hydroxyapatite, the model
      inorganic compound for the calcified deposits, was precisely monitored in a
      reactor containing supersaturated calcium phosphate solutions in which the heart
      valves were immersed after being treated with glutaraldehyde and mounted on
      special racks. The precipitation process, accompanied with proton release in the
      solution, was monitored by a pair of glass-saturated calomel electrodes. Upon
      initiation of the formation of calcium phosphate deposits, the supersaturation in
      the working solution was reestablished through the addition of titrant solutions
      made with the appropriate concentration to compensate for the ions precipitated.
      With this methodology, not only the rates were measured very precisely but also
      the nucleation capability of the various substrates could be evaluated. Moreover,
      it was possible to identify the formation of intermediate calcium phosphate
      phases formed during the calcification process. Valves previously treated with
      glutaraldehyde were shown to nucleate octacalcium phosphate, which at lower
      supersaturations converted to the thermodynamically more stable hydroxyapatite.
      The rates measured were found to depend on the solution supersaturation, while
      the apparent order of the precipitation process was found to be 1.

PMID- 9283963
TI  - UV curable bioadhesives: copolymers of N-vinyl pyrrolidone.
AB  - A series of UV curable bioadhesives was prepared from copolymers of N-vinyl
      pyrrolidone with four different comonomers: 2-acrylamido methyl 1-propane
      sulfonic acid, vinyl succinimide, glycidyl acrylate, and 2-isocyanatoethyl
      methacrylate. The developed bioadhesives demonstrated a fast UV-induced setting
      with a set time of about 3 min. Bond strength between the bioadhesive and porcine
      intestine specimen was determined by the peel test. These bioadhesives can
      provide improved adhesion values up to 4.6 N/m of 180 degrees peel strength
      compared to five different commercial bioadhesives (values ranging from 0.52 to
      3.04 N/m). In addition, the fully hydrated UV curable bioadhesives have shown a
      high water uptake ranging from 25 to 350 wt% and equilibrium water content
      ranging from 20 to 100 wt%. Because N-vinyl pyrrolidone is a monomer all these
      copolymers are expected to retain good biocompatibility. Obtained promising
      results of peel strength and water uptake clearly suggest that the developed
      bioadhesives have a strong potential for many medical applications such as single
      layered hydrogel wound dressings and tissue adhesives.

PMID- 9283964
TI  - Use of nonporous polytetrafluoroethylene prosthesis in combination with
      polypropylene prosthetic abdominal wall implants in prevention of peritoneal
      adhesions.
AB  - One of the drawbacks of using macroporous polypropylene prostheses in the repair
      of the abdominal wall is the formation of adhesions with the viscera. However,
      polytetrafluoroethylene (PTFE) has low adhesion formation, although it provides
      less resistance to traction in the repaired zone. The aim of the present study
      was to reduce the formation of adhesions to a polypropylene implant Prolene (PL)
      by introducing a nonporous expanded PTFE layer (Preclude Dura-Substitute) (PR)
      between the polypropylene prosthesis and the abdominal viscera. The scarring
      process and resistance to traction in the repaired zone were also evaluated.
      Thirty-six rabbits were divided into three groups and were treated as follows:
      group I, a PR patch (7 x 5 cm) was secured to the parietal peritoneum; group II,
      an abdominal wall defect (7 x 5 cm) was created and repaired using a PL patch;
      group III, an abdominal wall defect was as in group II and was repaired using a
      combined PR/PL prosthesis. Specimens were evaluated at 14, 30, 60, and 90 days
      postimplant for extent of adhesion formation and morphological analysis was
      performed using light and scanning electron microscopy. Biomechanical resistance
      of the implant was evaluated using strips comprising prosthetic material and
      anchorage tissue. Group I and group III prostheses showed loose adhesions only,
      but group II adhesions were firmly attached. The mean surface areas covered by
      adhesions were 0.08 cm2 (group I), 7.67 cm2 (group II), and 0.1 cm2 (group III).
      PR implants (group I) were encapsulated by organized tissue. In group II the
      formation of disorganized tissue invading the prosthesis was observed. In group
      III the PR impeded the growth of disorganized scar tissue and the lower surface
      of the implant was covered by an orderly neoperitoneum. Resistance to traction of
      the double implants (group III) (mean +/- SD, 33.32 +/- 0.9 N) was similar to
      that of the Prolene implants (group II) (33.76 +/- 0.46 N) (Mann-Whitney U test,
      p < 0.05). We concluded the presence of a PR layer between the PL implant and
      viscera greatly reduced the incidence of adhesion formation without affecting the
      high resistance to traction provided by the PL implant or the evolution of the
      scarring process.

PMID- 9283965
TI  - Shapes and dimensional characteristics of polyethylene wear particles generated
      in vivo by total knee replacements compared to total hip replacements.
AB  - Periprosthetic tissue was obtained at revision surgery from 10 posterior cruciate
      retaining total knee replacement cases (five different manufacturers). The
      tissues were hydrolyzed and polyethylene particles were isolated from each case.
      Individual particles were analyzed by scanning electron microscopy combined with
      computerized image analysis. For comparison, periprosthetic tissues from 10 total
      hip replacement cases (six different manufacturers) were processed and analyzed
      simultaneously with identical methods. The morphologies of the isolated
      polyethylene particles from total knee specimens were distinctly different. There
      was more variety of size, shape, and texture in the total knee particles.
      Submicron granules were less prevalent than in hip specimens. Larger flake-shaped
      particles, some measuring several microns in length and width, were commonly seen
      in knee specimens but not hip specimens. The overall average area of particles
      from the total knees (1.2 microns2) was twice that of total hips (0.61 micron2)
      (p = 0.049). The average perimeter (p = 0.026) and length (p = 0.026) of total
      knee particles was also greater than the total hip particles. The proportion of
      the smallest polyethylene particles (those averaging 0.2 micron2) in the total
      knee specimens was significantly less than that in total hip specimens (p <
      0.0001). Although the large flake-shaped particles were visually striking, it is
      important to note that the majority of the wear particles from the total knee
      cases were also submicron. These differences in wear particle morphology and size
      are due to differences in the wear mechanisms of total knees and total hips. Size
      is only one parameter in wear particle bioreactivity. Other factors include
      particle shape, surface area, and possibly size/shape variability, as well as
      surface chemistry and particle concentration. Polyethylene wear particles are not
      unidimensional; they have complex and variable shapes. The combination of
      morphologic description and quantitative image analysis used in this study
      defines several differences in polyethylene wear particles from different
      sources.

PMID- 9283966
TI  - Fracture toughness of CoCr alloy-PMMA cement interface.
AB  - An unsymmetric cantilever geometry was used experimentally to determine the
      critical energy release rate values for cobalt chromium alloy
      polymethylmethacrylate cement (CoCr alloy-PMMA) interfaces with satin finished,
      grit blasted, and plasma sprayed surface treatments applied to the CoCr alloy.
      Critical energy release rates of 0.013, 0.181, and 0.583 N/mm were found for the
      satin finish, grit blasted, and plasma sprayed CoCr alloy-PMMA interfaces,
      respectively. A finite element model of the experimental test specimen was used
      to determine the crack tip phase angles (-8.73 degrees to -27.1 degrees) that
      indicated that the tensile load applied to the specimens resulted in a tensile
      (mode I) and in-plane shear (mode II) loading at the crack tip. The experimental
      data suggest that a satin finish CoCr alloy-PMMA interface has minimal resistance
      to crack propagation when compared to grit blasted or plasma sprayed surface
      treatments.

PMID- 9283967
TI  - Effect of mixing method on selected properties of acrylic bone cement.
AB  - The present study was an investigation of the effect of the method of mixing the
      constituents of CMW3 bone cement on selected physical and mechanical properties
      of the fully polymerized cement. Five such methods were used: hand mixing;
      "active" vacuum mixing; mixing in a machine that allowed simultaneous mechanical
      mixing and centrifugation; mixing using this machine followed by application of a
      "passive" vacuum; and application of a passive vacuum followed by mixing in the
      machine. It was found that the best overall results were obtained from cement
      that had been mixed using the second and fifth methods and the values of the
      properties were: density, 1220 to 1246 kg/m3; areal porosity, 0.02 to 7.04%;
      ultimate compressive strength, 84 to 112 MPa; ultimate compressive strain, 5.1 to
      6.4%; and compressive modulus of elasticity, 2249 to 2877 MPa.

PMID- 9283968
TI  - Assessment of wrought ASTM F1058 cobalt alloy properties for permanent surgical
      implants.
AB  - The behavior of the ASTM F1058 wrought cobalt-chromium-nickel-molybdenum-iron
      alloy (commonly referred to as Elgiloy or Phynox) is evaluated in terms of
      mechanical properties, magnetic resonance imaging, corrosion resistance, and
      biocompatibility. The data found in the literature, the experimental corrosion
      and biocompatibility results presented in this article, and its long track record
      as an implant material demonstrate that the cobalt superalloy is an appropriate
      material for permanent surgical implants that require high yield strength and
      fatigue resistance combined with high elastic modulus, and that it can be safely
      imaged with magnetic resonance.

PMID- 9283969
TI  - Hydroxyapatite modified chitin as potential hard tissue substitute material.
AB  - Calcium hydroxyapatite (HA) powder was incorporated into chitin solutions to form
      an intimate mixture. Upon casting of this mixture into molds of fixed dimensions
      with subsequent removal of solvent, HAs containing chitin flexible plates were
      produced. The amount of (HA) was varied from 10 to 50% by mass of HA. The elastic
      modulus, yield stress, and elongation to fracture, measured at a crosshead speed
      of 5 mm/min, of these HAs containing chitin flexible plates were evaluated. The
      amount of HA in the HA incorporated chitin was found to not significantly change
      the elastic modulus or elongation to fracture. However, a decrease in the maximum
      tensile stress with an increase in the HA content was found.

PMID- 9283971
TI  - Effect of alcoholic drinks on surface quality and mechanical strength of denture
      base materials.
AB  - The effect of pure alcohol as well as several alcoholic drinks on the static and
      dynamic strength and surface quality of denture base poly (methyl methacrylate)
      was investigated. Wetting tensile specimens with alcohol led to a reduction of
      their static strength by 16.1% and their fatigue strength by 14.3%. Polished
      specimens immersed in various alcoholic drinks with over 40% alcohol exhibited
      considerable surface corrosion, which was capable of reducing the fatigue
      strength of the material.

PMID- 9283970
TI  - Interactions of hydroxyapatite and fluorapatite particles on human osteoarthritis
      type B synoviocytes: effects on interleukin-1 alpha levels and lipoxygenase
      pathways.
AB  - We investigated the effects of the biomaterials hydroxyapatite (HAP) and
      fluorapatite (FAP) on cultured human osteoarthritis type B synoviocytes by
      analyzing interleukin-1 alpha (IL-1 alpha) production and arachidonic acid
      metabolism via lipoxygenase pathways. A portion of opsonized particles was
      endocytosed and was found in numerous phagolysosomes in human synoviocyte
      cytoplasms. The present study demonstrates that HAP and FAP calcined at 700
      degrees C induced a decrease in IL-1 alpha production but markedly decreased the
      synthesis of lipoxygenase products after 1-month incubation with the particles.
      This model will allow us to study the possible inflammatory response (arachidonic
      acid metabolism, proinflammatory cytokines) that can be induced by any
      biomaterials used in orthopedics.

PMID- 9283972
TI  - Directions for improvement of substitute heart valves: National Heart, Lung, and
      Blood Institute's Working Group report on heart valves.

PMID- 9283974
TI  - Atomic solvation parameters for proteins in a membrane environment. Application
      to transmembrane alpha-helices.
AB  - Several sets of atomic solvation parameters imitating: (i) nonpolar environment
      of hydrocarbon core of a membrane, (ii) aqueous solution, and (iii) weakly-polar
      solvents have been developed. The parameters have been incorporated into the
      ECEPP/2 and CHARMM force fields and employed in non-restrained Monte Carlo and
      molecular dynamics simulations of membrane-spanning alpha-helical peptides
      (segment A of bacteriorhodopsin, melittin). Through these simulations, the
      structure and energetics of the helices have been examined as a function of the
      solvation term in the potential energy function. For the peptides under study,
      the set (i) of atomic solvation parameters reveals good retention of the alpha
      helical conformation. By contrast, the simulations in vacuum or with the
      parameters imitating a polar solvent (sets (ii) or (iii)) show fast helix
      destabilization and tight packing of the structure accompanied by significant
      decreasing of the surface area accessible to solvent. Increased helical
      propensity for amino acid residues, population of side-chain rotamers as well as
      hydrogen-bonding pattern in nonpolar membrane-like environment agree well with
      available experimental and computational data. The problems related to further
      applications of the membrane-mimicking sets of atomic solvation parameters to
      simulations of membrane proteins and peptides are addressed.

PMID- 9283973
TI  - Materials and design of spinal implants--a review.
AB  - Man-made devices have been implanted into the body to relieve pain, to restore
      function, and to facilitate healing. The subjects of this review are the
      materials, and to a lesser extent, the design aspects of the numerous implants
      that are available to the surgeon in dealing with the ailing spine. Often it is
      the material aspects of such devices that are responsible for their success or
      failure. It may be that osteoconductive properties are desired for implants to
      assist fusion, whereas as inert a material as possible would be preferred for
      interpositional barriers. The materials composing the instrumentation used to
      facilitate healing of spinal fractures would ideally have properties that
      optimize strength and biocompatibility, while at the same time minimizing imaging
      artifacts and allowing a gradual transfer of load from the instrumentation to the
      vertebral body (i.e., viscoelastic effects). The application of biomaterials and
      biomechanics to the design of spinal devices is obvious; what may be more subtle
      though is what the in vivo interactions of these will be. The study of such
      aspects must continue in order to better evolve the designs and subsequent
      results of implanted spinal devices.

PMID- 9283976
TI  - Lipid-induced conformation of substance P.
AB  - Both the aqueous and the lipid-induced structure of a representative and widely
      studied tachykinin, substance P, has been investigated by two-dimensional proton
      nuclear magnetic resonance (2D 1H-NMR) spectroscopy and distance geometry
      calculations. Unambiguous NMR assignments of protons have been made with the aid
      of correlation spectroscopy (COSY and TOCSY) experiments and Overhauser
      enhancement spectroscopy (ROESY and NOESY; experiments. The NMR data obtained
      were utilized in a distance geometry algorithm to generate a family of structures
      which were further refined using restrained energy minimization. These data show
      that, while in water substance P appears to favour an extended chain
      conformation, in the presence of perdeuterated dodecylphosphocholine (DPC)
      micelles as membrane model system an amphiphilic helical conformation is induced
      in the mid-region (Q5-Q8) of substance P. The conformation adopted by substance P
      in the presence of DPC micelles yields a structural motif typical of neurokinin-1
      selective ligands, as proposed by Convert and coworkers (O. Convert et al.,
      Neuropeptides 19, 259-270 (1991)).

PMID- 9283975
TI  - Role of zinc in tRNA-acceptor stem binding by glutamyl-tRNA synthetase from
      E.coli: a molecular modeling study.
AB  - A model of the N-terminal half of glutamyl-tRNA synthetase from E. coli was
      constructed on the basis of similarity in sequence and function of Glutaminyl-
      and Glutamyl-tRNA synthetases. The glutaminyl-tRNA synthetase does not contain
      any zinc atom, but glutamyl-tRNA synthetase from E. coli contains one atom of
      zinc. The specific role of zinc is not yet known. In this article, molecular
      modeling is employed to show that the zinc atom is well outside the contact
      region of the acceptor stem of tRNA. The placement of a zinc atom at a
      significant distance from the tRNA acceptor stem indicates that the role of zinc
      is likely to be indirect and structural.

PMID- 9283977
TI  - The interaction of DNA with intercalating agents probed by sodium-23 NMR
      relaxation rates.
AB  - We have investigated the changes of Na-23 NMR spin-lattice and spin-spin
      relaxation rates of Na-DNA in dilute aqueous solutions, induced by the
      intercalating drugs ethidium, propidium, 6,7-dihydro
      pyrido[2',1':3,4]pyrazino[1,2-f]-phenanthridinediium dihydrate (dq2pyp) and by
      the electrostatic binder Mg2+. It has been found that the Na-23 spin-lattice
      relaxation is monoexponential, while the spin-spin relaxation follows a
      biexponential law. From the linear trends of the relaxation rates observed in the
      titration experiments of Na-DNA with the drugs we inferred the validity of a two
      site model in the fast exchange limit. The relaxation rates of sodium in the
      bound state have been estimated by using the fraction of bound sodium ions per
      phosphate charge, predicted by the counterion condensation theory, and the number
      of sodium ions released per bound drug, calculated from salt dependent
      equilibrium binding studies. The results show that the addition of the
      competitors slow down the broad component of the spin-spin relaxation rate of
      bound sodium in the order dq2pyp approximately propidium < ethidium < Mg2+. This
      reduction is shown to be due mainly to the decrease of the quadrupolar coupling
      constant for the slow motions, thus indicating a decrease of the average electric
      field gradient at the sodium ions close to the DNA surface. We also show that the
      broad component of the spin-spin relaxation rate linearly correlates with the
      relative non-polyelectrolyte free energy. This result is discussed in terms of
      the non-polyelectrolyte interactions affecting R2bB, which can be partitioned
      into stacking interaction and interactions involving the molecular moieties of
      the intercalators exposed to the solvent in the minor groove.

PMID- 9283978
TI  - Three-dimensional model for slipped loop RNA.
AB  - Earlier a three-dimensional model for a new unusual DNA conformation referred to
      as Slipped Loop Structure (SLS) has been suggested by us (1). The same type of
      folding could occur with RNA as well which means that one must use the A-form of
      the double helix rather than the B-one. The present paper discusses the creation
      of an all-atom stereochemically sound model for SLS-RNA. This calculated model,
      while possessing the same folding topology as the SLS-DNA, differs dramatically
      from the SLS-DNA by an overall folding geometry. It also differs radically from
      the RNA-pseudoknot and can thus be regarded as a new type of an RNA folding.

PMID- 9283979
TI  - Effect of glycine on DNA structural transitions induced by multivalent cationic
      compounds.
AB  - We have investigated the effect of glycine (an organic osmolyte) on several DNA
      transitions induced by Tb3+, spermidine3+ and spermine4+ addition, using light
      scattering, circular dichroism, UV spectroscopy and electric linear dichroism
      techniques. DNA condensation and B-Z transition by the three compounds is
      perturbed by glycine: more Tb3+, spermidine3+ and spermine4+ must be added to
      obtain the same extent of condensation or Z-form as compared to the behaviour in
      the absence of this organic osmolyte. However, according to the light scattering
      experiments, glycine has also a structural effect on the DNA condensation that
      could be explained by an influence of the medium dielectric constant on the
      morphology of particles formed or on the rate of the condensation process.
      Contrary to these transitions, the particular B-B'-psi transition resulting from
      the addition of Tb3+ to a DNA solution is not observed in the presence of
      glycine. Since the chelation of Tb3+ by the phosphate group and the N-7 of
      guanine is presumably responsible for this transition, the glycine effect could
      probably be explained by a perturbation of this chelation by the change in
      solvent polarity and the chelating ability of the organic osmolyte.

PMID- 9283980
TI  - Dynamics simulation of the interaction between the novel intercalator diethidium
      cation and B-form DNA.
AB  - Previous research has described the interaction between the novel molecule
      diethidium (2,7-diamino 9-[2,7 diamino 10-N-phenanthridium] 10-N-phenanthridium)
      (Figure 1) and B-form DNA. Our goal is the elucidation of diethidium as the first
      member of a novel class of drugs which are potential pharmaceutical agents. This
      class of potential drug molecules differs from previously known intercalators in
      the following ways: a) Its structure, that of two perpendicular planes, each
      known to have excellent intercalation properties, is novel b) Unlike known bis
      intercalators, the linker region length in diethidium is zero c) The geometry of
      the drug matches the geometry of the space available in the major groove d) The
      drug is shown to cause some vectorial disruption of DNA. For this paper, we have
      performed a series of 200 picosecond dynamics simulations on the complex formed
      between diethidium in the major groove and a dodecarner of double-stranded B-form
      DNA, CGCGAATTCGCG, and have shown that this complex has a intricate interaction.
      The DNA dodecamer is found to be in an intermediate A-B state, but, even in
      simulations as long as 1 nanosecond, the drug does not back-out or otherwise
      leave the intercalation site. The drug is found to be mobile within the
      intercalation site on timescales longer than 1 nanoscale. The mobility of the
      drug within the intercalation site has been predicted by our previous energy
      minimization studies.

PMID- 9283981
TI  - The study of the stability of Watson-Crick nucleic acid base pairs in water and
      dimethyl sulfoxide: computer simulation by the Monte Carlo method.
AB  - An extensive computer simulation of nucleic acid bases and Watson-Crick base
      pairs in a water cluster and DMSO cluster is performed by the Monte Carlo method.
      It is demonstrated that the unfavorable energetics of pair formation in a water
      cluster is determined by the significant destabilizing contribution of solvent to
      the energy of complex formation. It is shown that the formation of coplanar base
      pairs in a DMSO cluster is favorable. The DMSO cluster stabilizes A-U and A-T
      base pairs and the insignificant destabilization of the G-C base pair by a DMSO
      cluster is much less than the stabilization which occurs due to the attraction
      between bases.

PMID- 9283982
TI  - DNA binding studies and influence on the activity of DNA topoisomerases of bis
      netropsins: different effects of analogs containing cis and trans ethylene
      linkers.
AB  - Binding to DNA and synthetic duplex polymers of two bifunctional netropsins and
      effects on supercoiled plasmid DNA as well as their inhibitory potency on DNA
      topoisomerases have been investigated. Characteristic differences were found in
      the DNA binding properties of the two bis-netropsins containing a cis and trans
      tether as reflected by CD, thermal melting and sedimentation measurements. CD
      results indicate, that the bis-netropsins interact with DNA by a two-step binding
      mode depending on the ligand concentration. The trans bis-netropsin may form
      stable complexes with different DNA's at high salt concentration, whereas for cis
      bis-netropsin DNA complexes the second binding step is completely abolished. The
      variations in the DNA binding ability of trans and cis bis-netropsin show a close
      relationship to the differences observed in their inhibitory effects on DNA
      topoisomerases. It appeared that trans bis-netropsin more strongly blocks
      topoisomerase activity than the cis isomer and represents the most potent
      inhibitor of DNA gyrase. Differences in the DNA. binding ability of the bis
      netropsins and their inhibitory potency on topoisomerase activity are explained
      in terms of bidentate and monodentate binding mode of the trans and cis isomer,
      respectively.

PMID- 9283983
TI  - Liquid-crystalline structure of nucleic acids: effect of antracycline drugs and
      copper ions.
AB  - The formation of liquid-crystalline dispersions (L.C.D.) from double-stranded DNA
      and polynucleotide (NA) molecules complexed with a number of anthracycline
      derivatives was investigated. These drugs form two types of complexes (complex I
      and complex II) with NA, which differ in the mode of drug orientation in respect
      to the NA helical axis. When complex II forms, addition of copper ions causes
      bridging of neighboring NA molecules through polymeric copper-anthracycline links
      (Figure 1). This results in an extra-increase in the amplitude of the intense CD
      band, characteristic for complex II, in the drug absorption region. Comparison of
      data obtained for different analogs and derivatives of daunomycin, has shown that
      the presence of 4 coordinating oxygen atoms at positions 5,6 and 11,12 (or 1,12)
      of the anthracycline ring system represents the basic prerequisite for the
      formation of a long polymeric chelate bridge after addition of copper ions. A
      second requirement relates to the chemical and stereochemical properties of sugar
      residues at position 7. These are important for proper positioning of the
      neighboring anthracycline aglycones in the polymeric chelate bridges and for
      spatial fixation of Cu2+ ions. Base sequence of double-stranded polynucleotides
      plays, if any, a minor role in polymeric chelate bridge formation. The question
      concerning the sterical orientation of two neighbouring antracyclines in the
      linking bridges, formed between NA molecules fixed in the liquid-crystalline
      structure, remains open.

PMID- 9283984
TI  - A UV resonant Raman spectroscopic study of the interaction of metallic
      derivatives of tetrakis(4-N-methylpyridyl)porphine with polynucleotides.
AB  - Resonance Raman spectra excited at 257 nm are reported for the complexes of the
      Nickel, Cobalt and Zinc derivatives of Tetrakis(4-N-methylpyridyl)porphine with
      poly(dA.dT)2, poly(dA).poly(dT), poly(dG.dC)2 and poly(dG).poly(dC). These
      spectra are interpreted as evidence of multiple outside binding modes with
      poly(dA).poly(dT), and of evidence for an outside binding mode with Poly(dG.dC).
      Some results obtained for the zinc derivative with poly(dA).poly(dT) suggest a
      binding mode peculiar to this derivative.

PMID- 9283985
TI  - FTIR study on nucleotide analogues. 1. Spectral characterization of dinucleoside
      methylphosphonates and dinucleoside 5'-methylenephosphonates in solution and in
      solid phase.
AB  - Some conformational feature of dithymidine nucleotides containing natural 3'-->5'
      phosphodiester, methylphosphonate, or 5'-methylenephosphonate internucleotidic
      linkages were probed in solution and in solid phase using FTIR spectroscopy. A
      high similarity of the IR spectra in the region of 1800-1250 cm-1 indicates that
      all the investigated compounds have similar glycosidic torsion angels and the
      preferred conformation of the deoxyribose rings. However, small but significant
      differences between the Rp and Sp diastereomers of methylphosphonate analogue 5
      may suggest that the association or the hydration mode of these compounds may
      vary.

PMID- 9283986
TI  - Melting of cross-linked DNA: I. Model and theoretical methods.
AB  - Covalent and strong coordination binding to DNA of a large number of antitumour
      drugs and other compounds leads to interstrand cross-link formation. To
      investigate cross-link influence on double helix stability, two methods are
      developed for the calculation of melting curves. The first method is based on
      Poland's approach. It requires computer time proportional to u.N, where u is the
      average distance (in base pairs) between neighboring cross-links and N is the
      number of base pairs in the DNA chain. The method is more suitable when u is not
      large, and small loops formed by interstrand cross-links in melted regions
      strongly affect DNA melting. The computer time for the second method, based on
      the Fixman-Freire approach, does not depend on the number of cross-links and is
      proportional to I.N (I is the number of exponential functions used for a
      decomposition of the loop entropy factor). It is more appropriate when N and u
      are large, and therefore particular values of the entropy factors of small loops
      do not influence DNA melting behavior.

PMID- 9283987
TI  - Melting of cross-linked DNA: II. Influence of interstrand linking on DNA
      stability.
AB  - In the previous paper (D.Y. Lando, J. Biomol. Struct. Dynam, 15, 129-140 (1997))
      the melting of cross-linked DNA with N base pairs and omega interstrand cross
      links has been considered theoretically. In the present study on the basis of
      these results, two simple schemes are developed for the computation of melting
      curves of cross-linked DNA. The investigation of influence of interstrand linking
      on DNA stability has been carried out by computer simulation. It is shown that
      the relative concentration of cross-links, CCT = omega/N, their distribution
      along a DNA molecule, and particular values of the entropy factors of small loops
      formed by cross-links in melted regions strongly affect the DNA melting
      temperature, Tm. On the contrary, for DNA without cross-links, a ten-fold
      increase or decrease in the entropy factors of small loops does not cause the Tm
      variation. The comparison of the results of calculation with experimental data
      suggests that the majority of types of cross-link neither maintain ordered
      parallel orientation of bases in melted regions nor increase considerably the
      thermostability of cross-linked base pairs. Four different ways of influence of
      interstrand cross-linking on the DNA double helix stability are considered. It is
      shown that cross-linking significantly enhances the influence of single strand
      stiffness in melted regions on DNA melting behavior.

PMID- 9283988
TI  - Structural variability of A-DNA in crystals of the octamer d(pCpCpCpGpCpGpGpG)
AB  - We have determined the structure of the synthetic DNA octamer d(pCpCpCpGpCpGpGpG)
      in five different crystal forms by single crystal X-ray diffraction. One crystal
      belongs to the space group P4(3)2(1)2 with a = b = 41.77, c = 25.15 A, whereas
      all others have the space group P2(1)2(1)2(1) with progressively decreasing unit
      cell volumes. In all crystals the octamer forms duplexes of A-DNA and all
      crystals display a similar packing mode, typical for A-DNA. The structure of the
      duplex varies from loose to very compact when going from one crystal form to
      another. The most compact form exhibits a volume of 995 A3 per base pair. Such a
      high density has never been found in A-DNA, being more characteristic of Z-DNA
      crystals. A comparison of the most with the least compact forms gives a RMS value
      of 1.7 A, with the distance between the phosphate centers through the major
      groove being almost twice shorter in the compact form. The phosphate-phosphate
      separation across the major groove in the compact form is extremely small, 0.7 A.
      The helical parameters also vary significantly in the various crystal forms.
      Differences in the helical twist can reach 13 degrees in the same step of the
      octamer in different crystal forms. The results prove that A-DNA is structurally
      very variable and demonstrate that the local structure of the same DNA fragment
      can strongly depend on the crystal environment.

PMID- 9283989
TI  - A parallel-group comparison of astemizole and loratadine for the treatment of
      perennial allergic rhinitis.
AB  - The efficacy and safety of the two antihistamines, astemizole and loratadine,
      were compared in a double-blind study of 84 patients with perennial allergic
      rhinitis. Patients were randomized to receive orally either astemizole 10 mg once
      daily (n = 40) or loratadine 10 mg once daily (n = 44) for 1 week. No other
      antirhinitis medication was allowed during the study. By day 7 the mean daily
      symptom scores, recorded on diary cards, were lower in patients receiving
      astemizole than in those receiving loratadine for runny nose, itchy nose and
      sneezing, although not for blocked nose, and treatment differences only reached
      statistical significance for runny nose. After 7 days, 53.75% of patients on
      astemizole and 38.6% on loratadine were free of symptoms, and 87% of patients on
      astemizole described the treatment as good or excellent compared with 62% on
      loratadine. The present results suggest that astemizole may be more effective
      than loratadine in controlling symptoms of perennial allergic rhinitis.

PMID- 9283990
TI  - Cisapride in the long-term treatment of chronic gastroparesis: a 2-year open
      label study.
AB  - The effect of long-term cisapride therapy (20 mg orally three times daily for 2
      years) on gastric emptying and gastrointestinal symptoms was investigated in 30
      patients with severe gastroparesis (24 idiopathic, 6 diabetic). Symptoms were
      assessed every 2 months, using an overall symptom score based on six symptoms
      (anorexia, nausea, vomiting, pain, early satiety and bloating), and a 2-year mean
      overall symptom score was used for analysis. Gastric emptying was measured at 0,
      6, 12, 18 and 24 months. Of the 24 patients who completed the study, 10 showed a
      significant improvement in gastric emptying (P < 0.05) and felt improved on
      therapy, seven patients showing a > 20% improvement in overall symptom score
      compared to baseline. Results for 15 patients who underwent at least one follow
      up gastric-emptying test showed only a weak correlation between individual
      symptom score and gastric emptying (r = 0.40). Thus long-term cisapride therapy
      at the study dose produced long-term symptomatic improvement in 42% of patients
      with severe gastroparesis, with sustained acceleration of gastric emptying for up
      to 2 years.

PMID- 9283992
TI  - Diagnostic problems in chronic eosinophilic pneumonia.
AB  - To identify the problems involved in the diagnosis of chronic eosinophilic
      pneumonia (CEP), clinical findings were analysed for 43 patients diagnosed
      clinically or pathologically with CEP during the past 10 years. About 28% of
      patients showed peripheral blood eosinophilia and a typical pattern of pulmonary
      oedema on chest X-ray at initial examination. Eosinophilia was demonstrated in
      peripheral blood in 86% of patients, in bronchoalveolar lavage (BAL) in 100%, and
      in transbronchial lung biopsy (TBLB) specimens in 64% of patients. Peripheral
      blood tests, BAL, and TBLB were all positive for eosinophilia in 60% of patients.
      BAL was the single test most likely to be positive among the diagnostic tests
      used in the present study. When CEP is suspected clinically, an understanding of
      which site is examined by each of the diagnostic tests and of the likelihood of a
      positive result in each test will facilitate the selection of the most
      appropriate tests for individual patients.

PMID- 9283993
TI  - Cleavage of unfertilized eggs after repeated administration of human chorionic
      gonadotrophin to hamsters.
AB  - The proportions of unfertilized eggs in the oviducts, showing abnormal cleavage,
      were examined in hamsters given single or repeated doses of 30 i.u. human
      gonadotrophic hormone for the induction of ovulation. In control animals (n = 7),
      1.7% of the total ovulated eggs were morphologically abnormal unfertilized eggs
      showing cleavage. The proportions of unfertilized eggs that were abnormal in the
      groups of seven hamsters treated with one, two or three doses of the
      gonadotrophin were 20.4%, 19.4%, and 30.4%, respectively. The proportion of
      unfertilized eggs showing abnormal cleavage thus appeared to increase with
      repeated administrations of gonadotrophin.

PMID- 9283991
TI  - Efficacy of lansoprazole against peptic ulcers induced by non-steroidal anti
      inflammatory drugs: endoscopic evaluation of ulcer healing.
AB  - Beyond the obvious step of limiting use of non-steroidal anti-inflammatory drugs
      (NSAIDs), the treatment of ulcers induced by NSAIDs remains controversial. We
      evaluated the efficacy of the proton-pump inhibitor lansoprazole on NSAID-induced
      ulcers. Ulcers were endoscopically diagnosed in 47 NSAID users. These patients
      received 30 mg/day lansoprazole, orally, for 6 or 8 weeks (6 weeks for duodenal
      ulcers and 8 weeks for other ulcers). Ulcer healing was assessed using an
      established classification system. The presence of immunoglobulin G antibody
      against Helicobacter pylori was also evaluated. The antibody was present in the
      sera of 51% of patients (24/47). Most of the ulcers reached scarring stages S1
      (healing) or S2 (good healing), and the S2 healing rate was 35%. Two H. pylori
      seropositive patients did not reach these stages; their ulcers were improved by
      H. pylori eradication therapy, followed, in one case, by medication with
      misoprostol. Lansoprazole seemed to be useful for most patients with NSAID
      induced ulcers, but a few needed additional treatments.

PMID- 9283994
TI  - Colloidal silicic acid for the treatment of psoriatic skin lesions, arthropathy
      and onychopathy. A pilot study.
AB  - In a randomized, double-blind study, patients with chronic plaque-type psoriasis
      were either treated with 30 ml colloidal silicic acid gel, orally, daily, and
      topically with the same gel (n = 15), or were treated identically with placebo
      gel (n = 15) for 3 months. One stable psoriatic lesion on the knee or elbow was
      treated topically and followed throughout the study. Five patients in the treated
      group and seven controls had psoriatic arthropathy and 11 treated patients and 12
      controls had psoriatic onychopathy. Three treated patients and six controls
      withdrew because of skin irritation or lack of efficacy. In the treated group
      there were clear improvements in scaling, induration and erythema after
      treatment. The nail changes were cured in five of 10 evaluable patients in the
      treated group and joint pain was reduced by almost half in the four evaluable
      patients with arthropathy. There were no such improvements in the placebo group.

PMID- 9283995
TI  - Sensitivity of antibacterials of Staphylococcus aureus isolated from impetigo
      patients.
AB  - We measured the sensitivity to antibacterials of Staphylococcus aureus isolated
      from impetigo lesions during one year (from July 1994 to July 1995). The largest
      number of strains was resistant to gentamicin, followed by erythromycin. Few
      methicillin-resistant S. aureus strains were isolated and few strains were
      resistant to more than one drug. We conclude that nadifloxacin and tosufloxacin
      are likely to be most effective against S. aureus, but fusidic acid is more
      suitable for the treatment of children.

PMID- 9283996
TI  - Fluconazole treatment of neonates and infants with severe fungal infections.
AB  - A total of 24 neonates and infants, aged from 2 days to 10 months, received
      treatment with intravenous fluconazole for microbiologically documented or
      presumed fungal infection. The mean fluconazole dosage was 6 mg/kg/day (range 2
      16 mg/kg/day) and the mean duration of therapy was 25 days (range 5-72 days).
      Efficacy was evaluated in neonates with proven fungal infections, as documented
      by the presence of pathogen at baseline. A positive clinical response was
      achieved in 23 of the 24 clinically evaluable patients (96%); eradication of the
      fungal organism was also achieved in 23 of the 24 evaluable patients (96%).
      Adverse events occurred in two patients (8%) but therapy was not discontinued in
      either patient. The present results confirm the efficacy and safety of
      fluconazole in the treatment of neonates and infants with severe fungal
      infections.

PMID- 9283998
TI  - The interdisciplinary nature of surgical research.

PMID- 9283997
TI  - Antithymocyte globulin for a patient with systemic lupus erythematosus
      complicated by severe pancytopenia.
AB  - The clinical use of antithymocyte globulin is rarely reported in patients with
      rheumatic diseases. We describe the use of this agent in a patient with systemic
      lupus erythematosus who concomitantly developed severe pancytopenia. High-dose
      methylprednisolone therapy had been unsuccessful in controlling either the
      disease exacerbation or the pancytopenia. Antithymocyte globulin and cyclosporin
      A were therefore administered to achieve immunosuppression. The exacerbation of
      disease activity was gradually lessened, except for persistent thrombocytopenia
      and anaemia. Severe and persistent immunosuppression, however, led to a fatal
      brain abscess. The combined use of both antithymocyte globulin and cyclosporin A
      induced potent immunosuppression, and should be confined to selected patients
      with systemic lupus erythematosus, and administered under detailed monitoring.

PMID- 9283999
TI  - Liver tumor ablation techniques.
AB  - Despite advances in surgical technique, patients with primary and secondary liver
      tumors remain a difficult management problem, as most tumors are unresectable at
      presentation. Alternative therapies, involving the in situ destruction of liver
      tumors, have recently come under scrutiny as palliative options. Percutaneous
      ethanol injection and cryosurgery have been advocated, but both have associated
      technical difficulties and adverse effects. Novel liver tumor ablation techniques
      have recently been developed that work via the induction of localized
      hyperthermia. There is mounting evidence to support a hypothesis that cancer
      cells are more selectively sensitive to heat than are normal cells, due to the
      poor blood supply of neoplastic tissue and the decreased vasodilatation capacity
      of the neovascular bed. These ablative modalities induce a variable degree of
      tumor necrosis in unresectable tumors, and therefore may provide useful
      palliation. Clinical trials are needed to determine the true nature and degree of
      any palliative benefit. In addition, the determinants of treatment efficacy and
      the predictability of the necrotic zone must be better understood before these
      techniques can be contemplated as alternatives to liver resection for cure.

PMID- 9284000
TI  - Plasma thromboxane B2 concentrations and pulmonary vascular resistance during
      lung reperfusion.
AB  - The purpose of this study was to measure the behavior of plasmatic thromboxane B2
      (pITxB2) after reperfusion of a glucose-insulin-potassium preserved lung. Seven
      adult mongrel dogs underwent a left lung allotransplantation. Hemodynamic changes
      including pulmonary artery pressure and cardiac output were measured. Pulmonary
      artery vascular resistance, systemic resistance, arterio-venous oxygen
      difference, and shunt were calculated. Immunoreactive arterial and venous plasma
      thromboxane B2 concentrations were measured at 0 (basal), 60, 120, and 180 min
      after reperfusion. Hemodynamic measurements were made after 5 min of occlusion of
      the right pulmonary artery and ventilation with 100% oxygen. Prepreservation, pre
      reperfusion, and posttransplant lung weights were obtained. All animals survived
      the procedure. Ischemic time was 14.72 (+/-0.31) h. Cardiac output, systemic
      arterial pressure, and arterio-venous oxygen difference decreased while systemic
      vascular resistance, pulmonary vascular resistance, and shunt increased during
      the study. Mean pulmonary artery pressure correlated with pulmonary vascular
      resistance (p < .01). Oxygen tension diminished significantly at 180 min after
      reperfusion. Mean basal pulmonary arterial TxB2 was 3589 (+/-424) pg/ml; mean
      plasma pulmonary venous TxB2 was 6578 (+/-1571) pg/ml. Pulmonary arterial to
      venous TxB2 ratio (a/vTxB2) increased from 0.70 at basal measurement to 0.83 at
      60 min, and 0.99 at 120 and 180 min after reperfusion (p < .05). Pulmonary
      arterial TxB2 had a positive correlation with mean pulmonary artery pressure (p <
      .05); also, a/v pITxB2 correlated with pulmonary vascular resistance (r = .616, p
      < .01). Mean post-reperfusion lung weight increase was 74.88% (45.37 g). In
      conclusion, pITxB2 a/v ratio ratio increases after reperfusion of a 14-h
      preserved lung; pulmonary vascular resistance significantly increases after 180
      min of reperfusion and correlates with the increase in pITxB2 a/v ratio.

PMID- 9284001
TI  - Effects of hydroxyethyl starch-deferoxamine on arachidonic acid metabolism and
      small bowel wall perfusion in early sepsis.
AB  - The effects of hydroxyethyl starch-conjugated deferoxamine (HES-DFO), a
      macromolecular iron chelator, were investigated on eicosanoid release and bowel
      wall perfusion following cecal ligation puncture (CLP) in rats. Animals were
      randomly given an intravenous dose of 3.0 ml of HES-DFO or either vehicle (HES)
      or 9.0 ml saline immediately following completion of the CLP procedure. At 30,
      60, 120, and 240 min after sepsis induction, blood pressure and bowel perfusion
      were measured. The animals were sacrificed and blood was collected for subsequent
      analysis of thromboxane, prostacyclin, and prostaglandin F2 alpha. The tissue
      content of energy-rich phosphates was determined in small-bowel samples at each
      time point. The antioxidative HES-DFO therapy did not diminish the eicosanoid
      release after CLP when compared with either HES-treated or saline-infused rats.
      However, treatment with the polymeric iron chelator resulted in an impaired bowel
      wall perfusion that was not reflected in alterations in total adenine nucleotide
      content or in energy charge. Considering hemodynamic and biochemical endpoints,
      these results are contradictory to the hypothesis that iron-driven oxygen
      radicals are major determinants of the eicosanoid release that is elevated
      following CLP-induced sepsis.

PMID- 9284002
TI  - Renal artery occlusion model in dogs for the evaluation of thrombolytic agents.
AB  - The purpose of this study was to develop a model of renal artery occlusion and to
      investigate the effects of various thrombolytic agents on an acute occlusion of
      the renal artery with respect to ischemic tolerance of renal parenchyma. In order
      to do this, a thrombosis model in dogs (n = 36) was established and a total of 72
      dorsal renal arteries occluded using autologous clot material. For the in vitro
      preparing of a clot, autologous blood (20 mL) was withdrawn and 100 U thrombin
      immediately added. Then 1 mL of the clot material was injected into the dorsal
      branch of the exposed renal artery. The dogs were divided into 8 groups (2
      control groups, 6 therapy groups with local and systemic thrombolytic therapy).
      Thrombolysis was performed using urokinase, single-chain urokinase, and
      recombinant tissue-plasminogen activator. In all cases the clot preparation
      technique allowed complete and stable occlusion of the renal arteries. Local and
      systemic application of the thrombolytic agents, however, resulted in complete
      recanalization of the clot material in all study groups. Recombinant tissue
      plasminogen activator turned out to be the most effective agent in terms of
      recanalization time. The technique described allowed effective and reproducible
      artery occlusion for in vivo experimental work to study comparatively
      thrombolytic agents with respect to fibrin specificity, lytic efficacy, and side
      effects.

PMID- 9284003
TI  - Experimental study investigating the feasibility of a new method for laparoscopic
      indirect inguinal hernia repair.
AB  - With the progress in laparoscopic techniques in recent years, there is an
      increased interest in laparoscopic hernia repair. The laparoscopic indirect
      inguinal hernia repair with simple closure of the internal ring seems feasible in
      childhood inguinal hernia repair; however, this technique carries the risk of
      postoperative patent processus vaginalis. In this-study we investigated the
      possibility of avoidance of this complication by chemical obliteration of
      processus vaginalis with 6% iodine solution in rats. The study population was
      comprised of three groups: simple suture of the internal ring, iodine application
      plus simple suture of the internal ring, and iodine application alone. While
      processus vaginalis was anatomically closed in 75% of the rats in the iodine plus
      simple suture of the internal ring group, it was closed in 10% of the iodine
      application alone group and was not closed in the simple suture of the internal
      ring alone group. No histopathologic injuries to the testis or cord were detected
      attributable to iodine. Our study showed that simple suture of the internal ring
      is not sufficient for hernia repair. Laparoscopic chemical agent application in
      addition to simple suture of the internal ring may be beneficial for successful
      laparoscopic indirect inguinal hernia repair in children.

PMID- 9284004
TI  - Experimental use of somatosensory evoked potential for intraoperative
      identification of spinal cord blood supply.
AB  - The role of sensory evoked potentials (SEPs) to be used intraoperatively to
      reliably predict spinal cord ischemia, caused by interruption of intercostal and
      of lumbar and sacral arteries, was evaluated in a canine model. Two groups were
      assessed: (A) interruption of intercostal arteries (n = 6) and (B) interruption
      of all posterior branches (n = 6). SEPs were evaluated intraoperatively as
      control and interruption of posterior vessel groups, and at 18-22 h after
      surgery. Neurologic assessment was performed preoperatively and 18-22 h
      postoperatively by modified Tarlov criteria. Morphological assessments were also
      performed. The assessment of the groups demonstrated prolongation of latency and
      loss of amplitude of SEP, but individual changes of SEPs were poor predictors of
      paraplegia. Ultrastructural changes correlated with neurologic findings. SEPs
      were unreliable for intraoperative identification of vessels critical to spinal
      cord blood supply, possibly related to anatomically different blood supply of
      sensory and motor tracts.

PMID- 9284005
TI  - Fetal atrial septal aneurysm. Prenatal diagnosis by ultrasonography.
AB  - OBJECTIVE: To assess prenatal diagnosis by ultrasonography in five cases of fetal
      atrial septal aneurysm. STUDY DESIGN: Five cases of fetal atrial septal aneurysm
      were diagnosed prenatally by ultrasound. Postpartum fetal cardiac
      echocardiography was performed in three of five infants from the first to the
      fourth day of life. The medical records of the five cases were reviewed and
      analyzed after delivery. RESULTS: Echocardiograms confirmed atrial septal
      aneurysm in two of the three neonates. One of the two infants was also found to
      have a patent foramen ovale, and the other infant had patent duct arteriosis in
      addition to a patent foramen ovale. Two had fetal cardiac arrythmias that
      resolved after birth. CONCLUSION: Atrial septal aneurysm in fetuses may be a
      natural transition in spontaneous closure of the associated patent foramen ovale
      or septal defect. The same phenomenon has been found in children and infants. Due
      to the uniqueness of the fetal circulation, atrial septal aneurysm may predispose
      to fetal arrythmias.

PMID- 9284006
TI  - Uterine blood flow. Assessment in an intrauterine insemination program for
      unexplained infertility.
AB  - OBJECTIVE: To evaluate the diagnostic usefulness of color Doppler velocimetry for
      infertility treatment. STUDY DESIGN: Sixty-one women undergoing controlled
      ovarian hyperstimulation and intrauterine insemination with their husbands' semen
      due to unexplained infertility were enrolled in the study. The Doppler waveforms
      of the uterine artery, subendome-trial radial artery and intraovarian artery were
      analyzed around ovulation, and the calculated pulsatility indices (PIs) were
      correlated with subsequent pregnancy results. RESULTS: Those women who conceived
      exhibited a significantly lower uterine artery PI and higher frequency of
      positive diastolic blood flow in the subendometrial arteries shortly after
      ovulation. The PI of the intraovarian arteries prior to ovulation was also
      significantly lower in conception cycles than in nonconception cycles. Uterine
      artery PIs between different cycles correlated well in the same individual. Lower
      uterine artery impedance was noted in women receiving supplementation with human
      menopausal gonadotropins as compared to clomiphene citrate alone. CONCLUSION:
      Doppler velocimetry is a useful tool for evaluating uterine receptiveness in
      infertility treatment. Intrinsically poor uterine perfusion should be
      investigated in cases of unexplained infertility.

PMID- 9284007
TI  - Fetal intracranial hemorrhage. Imaging by ultrasound and magnetic resonance
      imaging.
AB  - OBJECTIVE: To describe the magnetic resonance imaging (MRI) findings associated
      with fetal intracranial hemorrhage and to compare them with ultrasound findings.
      STUDY DESIGN: In four pregnancies complicated by fetal intracranial hemorrhage,
      fetal imaging was carried out using T2-weighted fast spin echo sequences and T1
      weighted fast low angle shot imaging sequences and by transabdominal
      ultrasonography. RESULTS: An antepartum diagnosis of hemorrhage was made by
      ultrasound in one case and by MRI in two. Retrospectively, the hemorrhagic area
      could be identified from the MRI images in an additional two cases and from the
      ultrasound images in one case. In the cases of intraventricular hemorrhage, the
      MRI signal intensity in the T1-weighted images was increased in the hemorrhagic
      area as compared to the contralateral ventricle and brain parenchyma. In a case
      with subdural hemorrhage, T2-weighted MRI signals from the hemorrhagic area
      changed from low-to high-intensity signals during four weeks of follow-up. Better
      imaging of the intracranial anatomy was possible by MRI than by transabdominal
      ultrasonography. CONCLUSION: MRI can be used for imaging and dating fetal
      intracranial hemorrhages. Variable ultrasound and MRI findings are associated
      with this complication, depending on the age and location of the hemorrhage.

PMID- 9284008
TI  - Literature-filing system for vulvar conditions.
AB  - OBJECTIVE: To develop a classification system for the retrieval of stored
      material on various vulvar conditions. STUDY DESIGN: The major subject areas of
      vulvar conditions and management were identified. They were further classified
      into categories and subcategories. A numbering system was chosen for coding. The
      information was formatted to allow retrieval from the Internet in a framework
      ready for label printing. RESULTS: The classification system developed provides
      guidelines that are useful in making retrieval of stored material on various
      vulvar conditions more efficient. It can be expanded and personalized to fit the
      practitioner's needs and can be obtained from the Internet in the following
      manner by opening Netscape and entering the location:
      http:/(/)www.med.umich.edu/obgyn/vulva/ vulvalit.html. The filing system was
      formatted to allow standard, 5266, file-folder-sized label sheets to be inserted
      into the printer, allowing access to pretyped labels. A total of 464 labels will
      be printed. CONCLUSION: This system for retrieving vulvar information will be
      useful to many people, including clinicians, educators and researchers. The
      information is easily obtained from the Internet and printed in label form. It
      aids in the development of a system for life-long learning.

PMID- 9284009
TI  - Staging endometrioid adenocarcinoma. Clinical and financial comparison of
      laparoscopic and traditional approaches.
AB  - OBJECTIVE: To compare laparoscopically assisted surgical staging (LASS) of
      endometrioid adenocarcinoma with traditional surgical staging by laparotomy.
      STUDY DESIGN: A retrospective review of all cases of uterine cancer (n = 108)
      insured by one health maintenance organization during 1990-1995. During this
      period, 29 patients underwent successful LASS and were compared to 64 who
      underwent laparotomy for treatment of surgical stage I endometrioid
      adenocarcinoma. RESULTS: LASS was performed successfully in 29 of 32 attempted
      cases. All patients on whom LASS was attempted were found to have surgical stage
      I. Laparoscopic pelvic lymphadenectomy was highly successful, with no failures
      and a mean number of 14 nodes obtained. The overall complication rate was
      significantly higher for laparotomy than for LASS (28% vs. 7%, P < .001). The
      average length of stay for laparotomy was significantly higher than for LASS (5.1
      vs. 2.3 days, P < .001). CONCLUSION: LASS for stage I endometrioid adenocarcinoma
      is an attractive alternative to traditional surgical staging. It causes fewer
      complications and shortens the hospital stay.

PMID- 9284010
TI  - Carbohydrate metabolism. Evaluation in women with de novo hypertension in late
      pregnancy.
AB  - OBJECTIVE: To evaluate carbohydrate metabolism in both diabetic and nondiabetic
      women with de novo hypertension in late pregnancy. STUDY DESIGN: Sixty-nine
      nondiabetic pregnant women were studied: 33 with gestational hypertension, 15
      with preeclampsia and 21 normotensives in the control group. Eight women with
      gestational diabetes and hypertension were evaluated separately. Glucose and
      insulin serum levels were evaluated in the fasting state and during an oral
      glucose load. Glucose-independent parameters were used to evaluate insulin
      response, insulin activity and glucose tolerance in fasting and postglucose
      ingestion states. Student's t test was used. RESULTS: Fasting glycemia was lower
      in both groups with de novo hypertension in late pregnancy than in the control
      group. Glycemia was higher throughout the oral glucose load in gestational
      hypertension than in preeclampsia. Insulinemia during the oral glucose load was
      higher in gestational hypertension than in both the control and preeclampsia
      groups. Fasting corrected insulin response and glucose tolerance were higher in
      gestational hypertension and preeclampsia than in the control group. In the
      postglucose ingestion state, insulin activity and glucose tolerance was lower in
      gestational hypertension than in preeclampsia. Women with gestational diabetes
      and hypertension were very insulin resistant. CONCLUSION: Glucose tolerance was
      not only decreased but also increased in the fasting state in de novo
      hypertension in late pregnancy due to a high insulin response. In the postglucose
      ingestion state, the gestational hypertension trend was toward insulin resistance
      even though normal insulin activity occurs in preeclampsia. Gestational diabetes
      associated with gestational hypertension was characterized by high insulin
      resistance.

PMID- 9284011
TI  - Midtrimester pregnancy termination for fetal malformations. Use of intravaginal
      prostaglandin E2.
AB  - OBJECTIVE: To compare outcome differences and responses to treatment in
      pregnancies complicated by either major fetal malformations or previous fetal
      death in the second trimester. STUDY DESIGN: Data were analyzed from a
      computerized perinatal database and individual hospital records for singleton
      gestations between 14 and 23 weeks undergoing labor induction with prostaglandin
      E2 (PGE2) suppositories (20 mg intravaginally every three to five hours).
      RESULTS: Between January 1993 and June 1995, 65 pregnancies underwent induction
      of labor for either a lethal fetal malformation (38) or death (27). As compared
      with the fetal death group, the malformation group required more suppositories
      (median 4, range 1-10, versus median 3, range 1-6; P < .05) and needed a greater
      total dosage (77.5 +/- 38.5 mg versus 61.8 +/- 37.8 mg, P < .05). The mean time
      from initiation of treatment until delivery was two hours longer in the
      malformation group. There were no significant differences between the two
      treatment groups in incidence of maternal side effects or of retained placentas
      requiring operative intervention. CONCLUSION: Patients who undergo second
      trimester induction of labor for major fetal malformations using intravaginal
      PGE2 should be counseled that the dosage of the drug is greater and that labor
      may last longer than in pregnancies complicated by a previous fetal death.

PMID- 9284012
TI  - Pregnancy in infertile PCOD patients. Complications and outcome.
AB  - OBJECTIVE: To evaluate the complications and outcome of pregnancy in women with
      polycystic ovary disease (PCOD). STUDY DESIGN: The course and outcome of 47
      singleton pregnancies in women with well-documented PCOD were compared with those
      in 100 healthy controls. RESULTS: Women with PCOD had a significantly higher body
      mass index as compared to the control group (P < .05); however, the proportion of
      lean versus obese subjects in the two groups was similar. The incidence of an
      abnormal glucose challenge test, gestational diabetes mellitus and pregnancy
      induced hypertension was significantly increased in pregnant women with PCOD (P <
      .05). When lean PCOD subjects were compared with lean control subjects, the
      difference in the incidence of the above complications was still significant (P <
      .05). The incidence of pregnancy complications was similar when obese PCOD
      subjects were compared with obese controls. CONCLUSION: Women with PCOD were at
      increased risk of gestational diabetes and pregnancy-induced hypertension, and
      this risk appeared to be independent of body mass index.

PMID- 9284013
TI  - Evaluating a new intrauterine pressure catheter.
AB  - OBJECTIVE: To evaluate the performance and verify the safety of the Koala
      Intrauterine Pressure Catheter (IUPC) in clinical use. STUDY DESIGN: Twenty IUP
      Koala Catheters were placed in laboring women. IUPC monitoring provided
      diagnostic information in assessing the pressures generated by the myometrium
      during the labor and delivery process. Information was recorded pertaining to the
      catheters' safety, ease of use, accuracy, zeroing, drift and amnioinfusion
      capability. Comparisons were made to a preexisting IUPC. RESULTS: The Koala
      catheter was safe to introduce into the intrauterine cavity. There were no
      problems with amnioport communications, connectors, placental perforation,
      unusual patient discomfort or infections with either the Koala or Intran fluid
      filled system. The numerical ratings were compared using the Mann-Whitney test
      and showed no significant difference between the two groups in safety, zeroing
      and drift. A statistically significant difference at the .01 level for ease of
      use, accuracy and setup in favor of the Koala was found. CONCLUSION: Clinical
      study of the Koala Intrauterine Pressure Catheter vs. Intran and the other fluid
      filled catheters demonstrated the Koala to be as safe and as functionally
      effective as, or more effective than, standard IUPCs.

PMID- 9284014
TI  - Severe vulvar vestibulitis. Relation to HPV infection.
AB  - OBJECTIVE: To determine whether patients with human papillomavirus (HPV)
      associated vestibulitis present differently from patients with HPV-negative
      disease and whether the presence of HPV is a predictor of the outcome of surgical
      treatment by perineoplasty. STUDY DESIGN: Thirty-eight women with severe vulvar
      vestibulitis who underwent surgical perineoplasty were found to have HPV DNA in
      the vestibule by polymerase chain reaction. Thirty-six other women with severe
      vestibulitis had no HPV DNA in the surgical specimen. The two groups were
      compared with regard to demographic, social and medical variables as well as
      physical findings in the vestibule and response to operative treatment. RESULTS:
      Both groups were found to be similar in respect to age (mean 25.9 +/- 7.93 versus
      25.47 +/- 5.8, respectively), parity, education, smoking habits, contraceptive
      use, presence of primary vestibulitis, presence of dysuria and involvement of the
      whole vestibule (both anterior and posterior). More unmarried than married women
      were infected with HPV (P < .002). There was no significant correlation between
      the presence of HPV and the outcome of surgical treatment (P < .6, relative risk
      = 0.9, 95% confidence interval = 0.5-1.5). CONCLUSION: Although HPV DNA was found
      in more than half of women with vestibulitis, it appears to play no role in the
      presentation or response to surgical therapy for vulvar vestibulitis.

PMID- 9284015
TI  - Rectal sonography for diagnosing hematocolpometra. A case report.
AB  - BACKGROUND: Imperforate hymen is an uncommon defect. Ultrasound may be useful in
      diagnosing hematocolpos, which is a common complication of imperforate hymen. The
      rectal approach with the ultrasound probe is an excellent method in aiding the
      diagnosis when the transvaginal approach is not feasible. CASE: Imperforate hymen
      was suspected in an amenorrheic, 13-year-old girl who complained of cyclic lower
      abdominal pain. Her pubic hair and breast development were Tanner stage 3.
      Abdominal and pelvic examination confirmed a tender pelvic mass. A bluish,
      bulging hymen was noted. Abdominal ultrasound revealed a pelvic cystic mass.
      Rectal ultrasound confirmed the diagnosis of hematocolpometra. CONCLUSION:
      Transrectal sonography provides an excellent alternative to transvaginal
      ultrasound in cases where transvaginal ultrasound is not feasible or is
      impossible. The rectal approach is appropriate due to the close proximity to the
      pelvic organs and patient acceptance of the procedure.

PMID- 9284016
TI  - Medical treatment of interstitial pregnancy. A report of three unsuccessful
      cases.
AB  - BACKGROUND: Medical management of ectopic pregnancy is effective in selected
      cases and is recommended to treat interstitial pregnancy to avoid surgery that
      may limit future fertility. Although successful medical management of
      interstitial pregnancy has been reported, evidence does not support success rates
      equal to that in other ectopic locations. CASES: Four cases of interstitial
      ectopic pregnancy were identified. Only one of the four was successfully treated
      with medical therapy. Case 1 was a confirmed, 2.5-cm interstitial pregnancy that
      failed a multiple-dose methotrexate protocol. Case 2 was an unrecognized
      interstitial pregnancy that failed single-dose therapy. Case 3 was a rupture of a
      medically managed interstitial pregnancy despite complete resolution of serum
      human chorionic gonadotropin. A literature review demonstrated an overall
      combined failure rate of 35% (7/20). CONCLUSION: Compared with an isthmic or
      ampullary pregnancy, a disproportionate number of patients with interstitial
      pregnancy fail medical management and require emergency surgery. The presence of
      a documented interstitial pregnancy is not an absolute contraindication to
      medical management. Patients should be counseled that medical management of an
      interstitial pregnancy may not have the same rate of success as it does in other
      locations in the fallopian tube. Surgery in this case may be the preferred
      treatment option.

PMID- 9284017
TI  - Rudimentary uterine horn pregnancy. A case report on surviving twins delivered
      eight days apart.
AB  - BACKGROUND: Surviving twins were born to a woman with a unicornuate uterus having
      a noncommunicating rudimentary uterine horn; this was the first such case
      reported. Further, it is the first report on a multiple gestation with one twin
      delivered successfully by cesarean section and the second vaginally at a later
      date. CASE: The first twin in a unicornuate uterus was delivered via cesarean
      section at 28 2/7 weeks due to intractable preterm labor with breech
      presentation. The ipsilateral hypogastric and ovarian arteries were ligated
      intraoperatively to arrest myometrial hemorrhage. Continuing preterm contractions
      resulted in contralateral rudimentary uterine horn rupture eight days later,
      allowing successful vaginal delivery of the second twin. CONCLUSION: Neonatal
      survival in rudimentary uterine horn pregnancies is poor, occurring in only 11%
      of cases during the past half century. The probability of attaining a favorable
      outcome is increased if aggressive antenatal management is instituted after
      establishing an early prenatal diagnosis. In the case of dual-chamber uterine
      anomalies, it is possible to effect surgical delivery of one fetus while
      maintaining a second preterm fetus in utero. This maneuver can decrease preterm
      morbidity for later-born siblings and enhance neonatal survival.

PMID- 9284018
TI  - Fallopian tube and pulmonary sarcoidosis. A case report.
AB  - BACKGROUND: Female reproductive tract sarcoidosis is a rare clinical condition,
      especially when the fallopian tube is the site of involvement. A search of the
      medical literature revealed 22 cases of female genital tract sarcoidosis, with 6
      cases involving the fallopian tube. CASE: Sarcoidosis of the genital tract
      occurred in a woman with a 16-year history of pulmonary sarcoidosis. CONCLUSION:
      Since various diseases, including sarcoidosis and tuberculosis, cause similar
      histologic changes, obtaining bacteriologic proof is mandatory, for the diagnosis
      can have therapeutic and public health implications.

PMID- 9284019
TI  - Analytic listening, transference interpretation, and the emergence of infantile
      dependency: do we really need to "educate" patients about analysis?

PMID- 9284020
TI  - Fostering tolerance and creativity in the culture of psychoanalysis.

PMID- 9284021
TI  - Too Rankian for the Freudians, or too Freudian for the Rankians: Otto Rank's
      contributions to psychoanalysis in the 1920s.

PMID- 9284022
TI  - On love and lust in the countertransference.

PMID- 9284023
TI  - Psychoanalytic treatment of the borderline patient.

PMID- 9284024
TI  - Support groups for professional caregivers: a role for the contemporary
      psychoanalyst.

PMID- 9284025
TI  - Modifying psychoanalytic methods when treating the HIV-positive patient.

PMID- 9284026
TI  - Obsessive-compulsive disorders in neurosis and psychosis.

PMID- 9284027
TI  - The embedment-in-the-brain-circuitry phenomenon: implications for psychoanalytic
      treatment.

PMID- 9284028
TI  - Rinderpest in South Africa--100 years ago.
AB  - To commemorate the centenary of the outbreak of rinderpest in South Africa, the
      historical events leading up to and following this major epidemic are recounted.
      Its impact on livestock and human populations, as well as initial and eventual
      successful attempts to control it are discussed.

PMID- 9284029
TI  - Bartonella (Rochalimaea) henselae in southern Africa--evidence for infections in
      domestic cats and implications for veterinarians.
AB  - Substantial evidence has recently accumulated showing domestic cats to be the
      principal reservoirs of Bartonella henselae, the aetiological agent of human
      diseases including cat-scratch disease, bacillary angiomatosis, bacillary
      peliosis and a febrile bacteraemia syndrome. To determine the prevalence of
      antibodies reactive with Bartonella henselae in cats from southern Africa,
      indirect fluorescent antibody assays were carried out on feline sera from South
      Africa and Zimbabwe. Overall, 23% (39/171) of cats had antibody titres > or =
      1/64, with cats from Zimbabwe (24%; 28/119) having higher seroprevalences than
      those from South Africa (21%; 11/52) although this difference was not
      statistically significant. The implications of these findings for veterinarians
      in southern Africa are discussed.

PMID- 9284030
TI  - The comparative role of haemoglobinaemia and hypoxia in the development of canine
      babesial nephropathy.
AB  - Renal pathology associated with haemoglobinaemia resulting from Babesia canis
      infection is ascribed to haemoglobinuria, with or without a contribution from
      anaemic hypoxia. This study was undertaken to investigate the relative roles of
      haemoglobinaemia and hypoxia in renal function and pathology in the dog. Three
      groups of 6 dogs each were used over a 4-day period. The dogs in the 1st group
      were infused with homologous canine haemoglobin, anaemic hypoxia was induced in
      the 2nd group, and both treatments were applied in the 3rd group. Full
      urinalyses, serum urea and creatinine concentrations, fractional clearance of
      sodium and the activity of urine enzymes, were assessed daily. At the end of the
      trial period, the glomerular filtration rate (GFR) was determined and kidney
      specimens collected for light and electron microscopy. In the group with hypoxia
      only, the urine sediment contained more casts and a greater number of renal
      tubular epithelial (RTE) cells than in either of the other groups. Hypoxia
      resulted in greater enzymuria, suggestive of RTE cell pathology, whereas
      haemoglobinuria did not appear to have any effect on urine enzyme activity.
      Hypoxia resulted in a decreased GFR. Histological examination revealed a mild,
      single-cell tubular necrosis in the majority of the animals (all 3 groups), with
      granular casts in the hypoxic groups. There appeared to be a large individual
      variation in the ability of the kidney to handle infused haemoglobin. It was
      concluded that severe haemoglobinaemia did not induce a significant nephropathy,
      anaemic hypoxia appeared to cause a very mild nephropathy, and the combination of
      haemoglobinaemia and anaemic hypoxia did not exacerbate this change. These
      lesions were very different from those described in canine babesiosis.

PMID- 9284031
TI  - Cardiovascular and respiratory effects of detomidine in isoflurane-anaesthetised
      horses.
AB  - Anaesthesia was induced in horses (n = 6) with a mixture of thiopentone and
      guaiphenesin and maintained by mechanical ventilation with a mixture of oxygen,
      air and isoflurane. Inspiratory and end-expiratory concentrations of oxygen,
      carbon dioxide and isoflurane were measured. Electrocardiography was used to
      evaluate heart rate and rhythm. Mean systemic arterial pressure (SAPm), pulmonary
      artery pressure (PAPm), right atrial pressure (RAPm) and pulmonary capillary
      wedge pressure (PCWP) were measured directly. Cardiac output was determined using
      the thermodilution method. Microcirculation in the upper triceps brachii muscle
      was estimated using laser Doppler flowmetry. Blood gas values, pH and haemoglobin
      concentration (Hb) were determined in arterial and mixed venous blood. Baseline
      values were taken after stabilisation of anaesthesia and were statistically
      compared to values obtained after an intravenous bolus of detomidine (10
      micrograms/kg) had been injected at Time 0. Samples were then collected at 2, 10,
      20, 30, 40 and 50 min. End-expiratory concentration of isoflurane was maintained
      at 1.8% during the experimental period described above. Thereafter, the
      isoflurane concentration was reduced to 1.3% and samples were collected at 60, 70
      and 80 min. Detomidine caused a significant reduction of heart rate (HR), cardiac
      index (CI), oxygen transport (O2TR) and a significant elevation of the SAPm,
      systemic vascular resistance (SVR) and coefficient of utilisation of oxygen
      (O2CU) at 2 min. A significant reduction in HR, CI, SAPm, Hb, content of oxygen
      in arterial blood (CaO2) and O2TR and a significant elevation of O2CU were
      observed 10-50 min after the injection of detomidine. Reduction of the isoflurane
      end-expiratory concentration to 1.3% was followed by a progressive improvement of
      the SAPm, CI and muscle perfusion towards the baseline values. Further reduction
      of Hb and CaO2 as compared to the baseline values was observed during the period.
      The data suggest that detomidine potentiates some of the cardiovascular effects
      of isoflurane in horses.

PMID- 9284032
TI  - A sero-epidemiological survey of equine piroplasmosis in the northern and eastern
      Cape Provinces of South Africa.
AB  - Serum samples from yearling Thoroughbred horses (n = 176) in the magisterial
      districts of Colesberg, Venterstad, and Wodehouse in the Northern and Eastern
      Cape Provinces were collected between September and November 1995 to determine
      the prevalence of antibodies to Babesia equi and Babesia caballi in these
      regions. Samples were examined for specific antibodies using the indirect
      fluorescent antibody test. The 95% confidence intervals for the prevalence of
      serum antibodies in the 3 districts combined varied from 47% to 61% for B. equi
      and from 26% to 40% for B. caballi. Antibody prevalence did not correlate with
      the known distributions of the tick vectors (Rhipicephalus evertsi evertsi and
      Hyalomma truncatum). Colts had a significantly higher prevalence of antibodies
      against B. caballi than fillies. No such difference could be determined for B.
      equi.

PMID- 9284033
TI  - The effect of selenium supplementation during the early post-mating period on
      embryonic survival in sheep.
AB  - The effect of selenium (Se) supplementation of ewes with blood Se concentrations
      ranging between 100-200 ng/ml on embryonic survival during the early post-mating
      period (days 15-35) was studied in 4 trials. In the 1st 2 trials 137 ewes were
      used in 1991 and 118 in 1992. After being mated as a single flock, these ewes
      were stratified randomly into 3 groups. One group served as a control, the 2nd
      was injected with 1 ml Deposel (containing 50 mg Se as Ba selenate) and the 3rd
      group injected with 1 ml containing 1 mg Se as Na selenite. During 1991,
      supplementation was administered immediately after the mating period. It was
      postponed by 14 days in 1992. Parenteral Se supplementation reduced (p < 0.10)
      the number of ewes that lambed by > 19% during 1991 but not during 1992. The
      number of ewes producing twins was unaffected. In Trials 3 and 4 there was a
      consistent indication that parenteral Se supplementation of pregnant ewes between
      15-35 days after mating resulted in a reduced (22-40%) embryonic survival rate,
      although significant (p < or = 0.10) differences were only observed after the
      pooling of treatments receiving parenteral Se supplementation. Drenching of ewes
      with 50 mg Se as Na selenite resulted in a similar tendency. Biochemical
      appraisal of the blood, kidney and liver Se status of ewes failed to reveal toxic
      levels. The possible mechanisms involved in impaired embryonic survival are
      unclear. Supplementation of ewes during the 1st month of pregnancy with
      parenteral Se preparations is not recommended.

PMID- 9284034
TI  - Modified apparatus for collection of free-flow urine from mares.
AB  - An apparatus for collection of free-flow urine from female horses is described.
      This apparatus is a modification of a similar device described previously. It
      allows the collection of voided urine from adult female horses without confining
      them to metabolic stables or resorting to invasive procedures like bladder
      catheterisation. It is relatively easy to use after a short adaptation period.

PMID- 9284035
TI  - Albizia versicolor poisoning of sheep and goats in Malawi.
AB  - A report is given of the 1st confirmed outbreak of Albizia versicolor poisoning
      in Malawi and the 1st natural outbreak reported in sheep and goats. Approximately
      800 animals are estimated to have died over a 9-year period on a government farm
      near Lake Malawi. Deaths occurred exclusively from August to December when ripe
      dry pods that fell to the ground were ingested. The major clinical signs were
      hyperaesthesia, wild running, lateral recumbency with rapid leg movements,
      nystagmus and rapid blinking. Approximately 75% of clinical cases made a full and
      rapid recovery. Sheep more often showed signs of poisoning than goats which was
      attributed to inherent susceptibility rather than selective feeding. The majority
      of animals affected were under 1 year of age. A series of experiments was
      conducted and all animals dosed with 6.4 g/kg or more of dry pods died with
      typical clinical signs. Although A. versicolor is well known to the local
      population there appeared to be no appreciation of its toxicity. Poisonings are
      probably rare under traditional management systems.

PMID- 9284037
TI  - The most often misdiagnosed eye diseases in dogs and cats.

PMID- 9284036
TI  - Multifocal Aspergillus terreus discospondylitis in two German shepherd dogs.
AB  - Multifocal fungal (Aspergillus terreus) discospondylitis was diagnosed in 2
      German shepherd dogs. In one dog, the aetiology was established by means of
      fluoroscopic-guided disc aspiration, cytology and culture of disc material and
      urine. Disseminated aspergillosis was confirmed at necropsy and A. terreus
      cultured from numerous organs in this dog. The aetiology in the other dog was not
      established until therapeutic failure forced surgical curettage of disc material
      from which the fungus was cultured. Ketoconazole therapy failed to effect an
      improvement, and at necropsy, disease was localised to the spinal column, with A.
      terreus cultured from the affected discs and associated vertebrae.
      Immunodeficiency was suspected in both cases. In the case of disseminated disease
      a reduced lymphocyte blastogenic response was demonstrated. Reduced IgA was shown
      in both cases. The German shepherd breed seems to be predisposed to Aspergillus
      infections and IgA deficiency.

PMID- 9284038
TI  - Rationale for early intervention in acute stroke.
AB  - Ischemic stroke occurs after an abrupt reduction in cerebral blood flow, usually
      related to thrombosis of an intracranial or extracranial artery. The presenting
      symptoms and signs of stroke vary greatly, depending on the region of the brain
      involved. Most individuals are unaware of the warning signs or symptoms of stroke
      and do not seek medical care immediately after stroke onset. Recently,
      thrombolytic therapy with intravenous tissue plasminogen activator (t-PA) has
      been shown to be effective for treatment of selected stroke patients if
      administered <3 hours after stroke onset. This therapy is now approved for stroke
      treatment, but relatively few stroke patients currently receive t-PA.
      Neuroprotective agents that improve the intrinsic ability of brain parenchyma to
      withstand ischemia are currently undergoing intensive clinical evaluation. Their
      development has been facilitated by significant scientific advances in the
      understanding of the pathophysiology of acute ischemic neuronal injury.
      Strategies aimed at interfering with these fundamental processes of ischemic
      neuronal injury have shown encouraging results in several preliminary clinical
      trials. However, these agents probably must also be administered within a few
      hours of stroke onset to be beneficial. Eventually, combined neuroprotective and
      thrombolytic therapy will likely be used for acute stroke treatment. This
      strategy's success will depend on increased public and professional education
      efforts dealing with stroke recognition, evaluation, and treatment.

PMID- 9284039
TI  - Atrial fibrillation and stroke: elucidating a newly discovered risk factor.
AB  - Atrial fibrillation is the most common sustained arrhythmia reported in the
      United States; an estimated 1-2 million Americans have chronic nonvalvular atrial
      fibrillation. This disorder is associated with a substantial risk of stroke.
      Several recent studies provide evidence that anticoagulation therapy is indicated
      for stroke prevention in patients with nonvalvular atrial fibrillation after
      recovery from a minor stroke. Clinical and echocardiographic criteria help to
      identify those patients who are at especially high risk for thromboembolic stroke
      and are candidates for carefully controlled anticoagulation. In an effort to
      reduce the possibility of thromboembolic events following either chemical or
      electrical cardioversion, the American College of Chest Physicians has recently
      prepared guidelines for the use of anticoagulation in the conversion of atrial
      fibrillation. The efficacy of antiarrhythmic drug therapy for cardioversion is
      often difficult to assess. Furthermore, it is associated with major risks,
      including heart failure and exacerbation of arrhythmia, and minor risks,
      including systemic intolerance. A new National Institutes of Health trial, Atrial
      Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM), will clarify
      the true risks and benefits of antiarrhythmic therapy for conversion of atrial
      fibrillation to sinus rhythm. Patients who cannot tolerate drug therapy may
      benefit from interruption of conduction in the bundle of His, followed by
      implantation of a permanent pacemaker, the use of radiofrequency energy ablation,
      or the implantation of an atrial defibrillator. Some patients may benefit from
      surgical procedures, such as left atrial isolation, the corridor operation, and
      the maze operation.

PMID- 9284040
TI  - Role of transesophageal echocardiography in the management of thromboembolic
      stroke.
AB  - Cardiac causes of stroke account for approximately 20% of strokes occurring in
      the United States. Transthoracic echocardiography (TTE) remains the cornerstone
      of non-invasive cardiac imaging, but transesophageal echocardiography (TEE) is
      superior for identifying potential cardiac sources of emboli, including left
      atrial thrombi, valvular vegetations, thoracic aortic plaque, patent foramen
      ovale, and spontaneous left atrial echocardiographic contrast. The diagnostic
      yield of TEE for potential cardiac causes of thromboembolism exceeds 50%. The
      impact of TEE on the clinical management of this group, however, remains
      undefined for most TEE-specific diagnoses. Thus, routine use of TEE in these
      patients has been questioned. The diagnostic yield is highest if the clinical
      history/physical examination suggests a cardiac source. However, the clinical
      scenario often dictates patient management, and TEE data are used to "validate"
      the clinical impression. Data from large, prospective, randomized
      (aspirin/warfarin) studies, in which TEE data are obtained from patients with
      suspected cardiac thromboembolism, are needed. If specific TEE diagnoses can be
      identified in which defined therapies are beneficial, "source of embolism" will
      continue to be the most common indication for TEE referral. In this paradigm, TEE
      (without initial TTE) will probably become a more direct diagnostic pathway.
      However, if these studies demonstrate that all patients with suspected cardiac
      source benefit from one (or no) therapy, independent of TEE data, referrals for
      TEE will decline. Results of ongoing randomized trials to evaluate the efficacy
      of TEE in patients with cryptogenic stroke or transient ischemic attack are
      awaited.

PMID- 9284041
TI  - Hyperacute stroke therapy with tissue plasminogen activator.
AB  - The past year has seen tremendous progress in developing new therapies aimed at
      reversing the effects of acute stroke. Thrombolytic therapy with various agents
      has been extensively studied in stroke patients for the past 7 years. Tissue
      plasminogen activator (t-PA) received formal US Food and Drug Administration
      approval in June 1996 for use in patients within 3 hours of onset of an ischemic
      stroke. Treatment with t-PA improves neurologic outcome and functional disability
      to such a degree that, for every 100 stroke patients treated with t-PA, an
      additional 11-13 will be normal or nearly normal 3 months after their stroke. The
      downside of t-PA therapy is a 6% rate of symptomatic intracerebral hemorrhage
      (ICH) and a 3% rate of fatal ICH. Studies are under way to determine whether t-PA
      can be administered with an acceptable margin of safety within 5 hours of stroke,
      to evaluate the therapeutic benefits of intraarterial pro-urokinase, and to
      assess the use of magnetic resonance spectroscopy to identify which patients are
      most likely to benefit from thrombolysis. Combination thrombolytic
      neuroprotectant therapy is also being studied. In theory, patients could be given
      an initial dose of a neuroprotectant by paramedics and receive thrombolytic
      therapy in the hospital. We are now entering an era of proactive, not reactive,
      stroke therapies. These treatments may reverse some or all acute stroke symptoms
      and improve functional outcomes.

PMID- 9284042
TI  - Transcription factors in eye development: a gorgeous mosaic?

PMID- 9284043
TI  - Mice lacking the ski proto-oncogene have defects in neurulation, craniofacial,
      patterning, and skeletal muscle development.
AB  - The c-ski proto-oncogene has been implicated in the control of cell growth and
      skeletal muscle differentiation. To determine its normal functions in vivo, we
      have disrupted the mouse c-ski gene. Our results show a novel role for ski in the
      morphogenesis of craniofacial structures and the central nervous system, and
      confirm its proposed function as a player in skeletal muscle development.
      Homozygous mutant mice show perinatal lethality resulting from exencephaly, a
      defect caused by failed closure of the cranial neural tube during neurulation.
      The timing of the neural tube defect in ski -/- embryos coincides with excessive
      apoptosis in the cranial neuroepithelium, as well as in the cranial mesenchyme.
      Homozygous ski mutants also exhibit a dramatic reduction in skeletal muscle mass,
      consistent with a defect in expansion of a myogenic precursor population. Nestin
      is an intermediate filament expressed in highly proliferative neuroepithelial
      stem cells and in myogenic precursors. Interestingly, we find decreased nestin
      expression in both the cranial neural tube and the somites of ski -/- embryos,
      compared with their normal littermates, but no reduction of nestin in the caudal
      neural tube. These results are consistent with a model in which ski activities
      are required for the successful expansion of a subset of precursors in the
      neuroepithelial or skeletal muscle lineages.

PMID- 9284044
TI  - A role for FGF-6 in skeletal muscle regeneration.
AB  - Fibroblast growth factor-6 (FGF-6) belongs to a family of cytokines that control
      cell proliferation, cell differentiation, and morphogenetic events. Individual
      FGFs are either expressed widely or in a restricted pattern during embryonic,
      fetal, and adult life. FGF-6 exhibits a restricted expression profile
      predominantly in the myogenic lineage. Important functions in wound healing and
      tissue regeneration have been proposed for various FGFs in the past, although
      data from knockout mice have not supported this view. We have inactivated the FGF
      6 gene in mice to investigate the role of FGF-6 in skeletal muscle development
      and regeneration. Wild-type mice up-regulate FGF-6 after skeletal muscle injuries
      and completely restore experimentally damaged skeletal muscle. In contrast, FGF
      6(-/-) mutant mice show a severe regeneration defect with fibrosis and myotube
      degeneration. The number of MyoD- and Myogenin-expressing activated satellite
      cells after injury were significantly reduced in mutants. This reduction was not
      caused by a reduced pool of quiescent satellite cells but presumably by a lack of
      activation or proliferation. Interbreeding of FGF-6(-/-) mutants with mdx mice
      leads to striking dystrophic changes in skeletal muscles of double homozygous
      mice characterized by myotube degeneration, the presence of large amounts of
      mononuclear cells, and deposition of collagen. RNA analysis revealed an up
      regulation of MyoD mRNA in mdx but not in FGF-6(-/-)/mdx double mutant mice. We
      conclude that FGF-6 is a critical component of the muscle regeneration machinery
      in mammals, possibly by stimulating or activating satellite cells.

PMID- 9284045
TI  - Overexpression of Stra13, a novel retinoic acid-inducible gene of the basic helix
      loop-helix family, inhibits mesodermal and promotes neuronal differentiation of
      P19 cells.
AB  - We report the cDNA cloning of Stra13, a novel retinoic acid (RA)-inducible gene
      from P19 embryonal carcinoma cells that encodes a basic helix-loop-helix (bHLH)
      protein that shows the highest sequence similarities to the Drosophila Hairy and
      Enhancer of split and mouse Hes proteins. Stra13 does not bind to the known
      consensus motifs (E-box and N-box) for bHLH proteins, but can repress activated
      transcription (through an alpha-helix rich domain) in part by interaction with
      general factors of the basal transcription machinery. During mouse embryogenesis,
      Stra13 RNA is expressed in the neuroectoderm, and also in a number of mesodermal
      and endodermal derivatives. Remarkably, overexpression of Stra13 in P19 cells
      results in neuronal differentiation in monolayer culture, under conditions where
      wild-type P19 cells only undergo mesodermal/endodermal differentiation. This
      neuronal differentiation is accompanied by an altered expression of mesodermal
      and neuronal markers, indicating that Stra13 could be one of the earliest RA
      target genes whose expression is required for repression of mesodermal/endodermal
      differentiation and/or induction of neuronal differentiation when P19 cell
      aggregates are exposed to RA. Our results raise the possibility that Stra13 could
      be involved as a repressor in a number of decision events occurring during
      differentiation of various cell lineages.

PMID- 9284047
TI  - The PAS domain confers target gene specificity of Drosophila bHLH/PAS proteins.
AB  - Trachealess (Trh) and Single-minded (Sim) are highly similar Drosophila bHLH/PAS
      transcription factors. They activate nonoverlapping target genes and induce
      diverse cell fates. A single Drosophila gene encoding a bHLH/PAS protein
      homologous to the vertebrate ARNT protein was isolated and may serve as a partner
      for both Trh and Sim. We show that Trh and Sim complexes recognize similar DNA
      binding sites in the embryo. To examine the basis for their distinct target gene
      specificity, the activity of Trh-Sim chimeric proteins was monitored in embryos.
      Replacement of the Trh PAS domain by the analogous region of Sim was sufficient
      to convert it into a functional Sim protein. The PAS domain thus mediates all the
      features conferring specificity and the distinct recognition of target genes. The
      normal expression pattern of additional proteins essential for the activity of
      the Trh or Sim complexes can be inferred from the induction pattern of target
      genes and binding-site reporters, triggered by ubiquitous expression of Trh or
      Sim. We postulate that the capacity of bHLH/PAS heterodimers to associate,
      through the PAS domain, with additional distinct proteins that bind target-gene
      DNA, is essential to confer specificity.

PMID- 9284046
TI  - The Pax2 homolog sparkling is required for development of cone and pigment cells
      in the Drosophila eye.
AB  - A new Drosophila Pax gene, sparkling (spa), implicated in eye development, was
      isolated and shown to encode the homolog of the vertebrate Pax2, Pax5, and Pax8
      proteins. It is expressed in the embryonic nervous system and in cone, primary
      pigment, and bristle cells of larval and pupal eye discs. In spa(pol) mutants, a
      deletion of an enhancer abolishes Spa expression in cone and primary pigment
      cells and results in a severely disturbed development of non-neuronal ommatidial
      cells. Spa expression is further required for activation of cut in cone cells and
      of the Bar locus in primary pigment cells. We suggest close functional analogies
      between Spa and Pax2 in the development of the insect and vertebrate eye.

PMID- 9284048
TI  - Inhibition of CDK activity and PCNA-dependent DNA replication by p21 is blocked
      by interaction with the HPV-16 E7 oncoprotein.
AB  - p21 inhibits cyclin-dependent kinase (CDK) activity and proliferating cell
      nuclear antigen (PCNA)-dependent DNA replication by binding to CDK/cyclin
      complexes and to PCNA through distinct domains. The human papillomavirus (HPV)-16
      E7 oncoprotein (16E7) abrogated a DNA damage-induced cell cycle arrest in vivo,
      despite high levels of p21. Using cell lysates and purified proteins we show that
      16E7 prevented p21 both from inhibiting CDK2/cyclin E activity and PCNA-dependent
      DNA replication, whereas the nononcogenic HPV-6 E7 had reduced effects.
      Inactivation of both inhibitory functions of p21 was attained through binding
      between 16E7 and sequences in the carboxy-terminal end of p21 that overlap with
      the PCNA-binding site and the second p21 cyclin-binding motif. These data imply
      that the carboxyl terminus of p21 simultaneously modulates both CDK activity and
      PCNA-dependent DNA replication and that a single protein, 16E7, can override this
      modulation to disrupt normal cell cycle control.

PMID- 9284049
TI  - The human papillomavirus E7 oncoprotein can uncouple cellular differentiation and
      proliferation in human keratinocytes by abrogating p21Cip1-mediated inhibition of
      cdk2.
AB  - The high risk human papillomaviruses (HPVs) are associated etiologically with the
      majority of human cervical carcinomas. These HPVs encode two viral oncoproteins,
      E6 and E7, which are expressed consistently in cervical cancers. The function of
      these viral oncoproteins during a productive infection is to ensure viral
      replication in cells that have normally withdrawn from the cell division cycle
      and are committed to terminal differentiation. Expression of the E7 oncoprotein
      has been shown to lead to the abrogation of various negative growth regulatory
      signals, including a p53-mediated G1 growth arrest, TGFbeta-mediated growth
      inhibition, and quiescence of suprabasal keratinocytes. Here we describe a novel
      mechanism by which E7 can uncouple cellular proliferation and differentiation. In
      contrast to normal, differentiating keratinocytes, HPV-16 E7-expressing
      keratinocytes show delayed cellular differentiation and elevated cdk2 kinase
      activity despite high levels of p21(Cip1) and association of p21(Cip1) with cdk2.
      We show that the HPV E7 protein can interact with p21(Cip1) and abrogate
      p21(Cip1)-mediated inhibition of cyclin A and E-associated kinase activities.
      Based on these findings, we propose that this capacity of the HPV E7 oncoprotein
      to overcome p21(Cip1)-mediated inhibition of cdk2 activity during keratinocyte
      differentiation contributes to the ability of E7 to allow for cellular DNA
      synthesis in differentiated keratinocytes.

PMID- 9284050
TI  - Autonomous and nonautonomous regulation of axis formation by antagonistic
      signaling via 7-span cAMP receptors and GSK3 in Dictyostelium.
AB  - Early during Dictyostelium development a fundamental cell-fate decision
      establishes the anteroposterior (prestalk/prespore) axis. Signaling via the 7
      transmembrane cAMP receptor CAR4 is essential for creating and maintaining a
      normal pattern; car4-null alleles have decreased levels of prestalk-specific
      mRNAs but enhanced expression of prespore genes. car4- cells produce all of the
      signals required for prestalk differentiation but lack an extracellular factor
      necessary for prespore differentiation of wild-type cells. This secreted factor
      decreases the sensitivity of prespore cells to inhibition by the prestalk
      morphogen DIF-1. At the cell autonomous level, CAR4 is linked to intracellular
      circuits that activate prestalk but inhibit prespore differentiation. The
      autonomous action of CAR4 is antagonistic to the positive intracellular signals
      mediated by another cAMP receptor, CAR1 and/or CAR3. Additional data indicate
      that these CAR-mediated pathways converge at the serine/threonine protein kinase
      GSK3, suggesting that the anterior (prestalk)/posterior (prespore) axis of
      Dictyostelium is regulated by an ancient mechanism that is shared by the Wnt/Fz
      circuits for dorsoventral patterning during early Xenopus development and
      establishing Drosophila segment polarity.

PMID- 9284053
TI  - Beta-galactosidase-labelled relay neurons of homotopic olfactory bulb transplants
      establish proper afferent and efferent synaptic connections with host neurons.
AB  - The vertebrate olfactory system has long been an attractive model for studying
      neuronal regeneration and adaptive plasticity due to the continuous neurogenesis
      and synaptic remodelling throughout adult life in primary and secondary olfactory
      centres, its precisely ordered synaptic network and accessibility for
      manipulation. After homotopic transplantation of fetal olfactory bulbs in
      bulbectomized neonatal rodents, newly regenerated olfactory neurons form
      glomeruli within the graft, and the efferent mitral/tufted cells of the
      transplant innervate the host brain, terminating in higher olfactory centres.
      However, the synaptic connections of the transplanted relay neurons within the
      graft and/or host's olfactory centres could not be characterized mainly because
      of lack of suitable cell-specific markers for these neurons. In this study, we
      have used olfactory bulbs from transgenic fetuses, in which the majority of the
      mitral/tufted cells express the bacterial enzyme beta-galactosidase, for
      homotopic olfactory bulb transplantation following complete unilateral
      bulbectomy. In the transplants, the cell bodies and terminals of the donor
      mitral/tufted cells were identified by beta-galactosidase histochemistry and
      immunocytochemistry at both light and electron microscope levels. We demonstrate
      that transplanted relay neurons re-establish specific synaptic connections with
      host neurons of the periphery, source of the primary signal and central nervous
      system, thereby providing the basis for a functional recovery in the lesioned
      olfactory system.

PMID- 9284051
TI  - Epigenetic silencing of RNA polymerase I transcription: a role for DNA
      methylation and histone modification in nucleolar dominance.
AB  - Nucleolar dominance is an epigenetic phenomenon that describes nucleolus
      formation around rRNA genes inherited from only one progenitor of an
      interspecific hybrid or allopolyploid. The phenomenon is widespread, occurring in
      plants, insects, amphibians, and mammals, yet its molecular basis remains
      unclear. We have demonstrated nucleolar dominance in three allotetraploids of the
      plant genus Brassica. In Brassica napus, accurately initiated pre-rRNA
      transcripts from one progenitor, Brassica rapa are detected readily, whereas
      transcripts from the approximately 3000 rRNA genes inherited from the other
      progenitor, Brassica oleracea, are undetectable. Nuclear run-on confirmed that
      dominance is controlled at the level of transcription. Growth of B. napus
      seedlings on 5-aza-2'-deoxycytidine to inhibit cytosine methylation caused the
      normally silent, under-dominant B. oleracea rRNA genes to become expressed to
      high levels. The histone deacetylase inhibitors sodium butyrate and trichostatin
      A also derepressed silent rRNA genes. These results reveal an enforcement
      mechanism for nucleolar dominance in which DNA methylation and histone
      modifications combine to regulate rRNA gene loci spanning tens of megabase pairs
      of DNA.

PMID- 9284054
TI  - Climbing fibre collaterals contact neurons in the cerebellar nuclei that provide
      a GABAergic feedback to the inferior olive.
AB  - The inferior olive provides climbing fibres to Purkinje cells in the cerebellar
      cortex and gives off axon collaterals to the cerebellar nuclei. The cerebellar
      nuclei contain GABAergic neurons that provide an inhibitory projection to the
      inferior olive and excitatory neurons that influence behaviour through various
      other premotor nuclei in the brainstem and diencephalon. Whether the olivary axon
      collaterals innervate the GABAergic neurons in the cerebellar nuclei is unknown.
      In the present study we investigated this projection in mice at the
      ultrastructural level using post-embedding GABA immunocytochemistry and
      anterograde and retrograde tracing of biotinylated dextrane amine and gold
      lectin. It is demonstrated that the olivary axon collaterals do not only
      innervate non-GABAergic neurons in the cerebellar nuclei, but also GABAergic
      nucleo-olivary cells, thus establishing a direct feedback loop to the inferior
      olive.

PMID- 9284052
TI  - Drosophila P-element transposase is a novel site-specific endonuclease.
AB  - We developed in vitro assays to study the first step of the P-element
      transposition reaction: donor DNA cleavage. We found that P-element transposase
      required both 5' and 3' P-element termini for efficient DNA cleavage to occur,
      suggesting that a synaptic complex forms prior to cleavage. Transposase made a
      staggered cleavage at the P-element termini that is novel for all known site
      specific endonucleases: the 3' cleavage site is at the end of the P-element,
      whereas the 5' cleavage site is 17 bp within the P-element 31-bp inverted
      repeats. The P-element termini were protected from exonucleolytic degradation
      following the cleavage reaction, suggesting that a stable protein complex remains
      bound to the element termini after cleavage. These data are consistent with a cut
      and-paste mechanism for P-element transposition and may explain why P elements
      predominantly excise imprecisely in vivo.

PMID- 9284055
TI  - GABA(A) receptor subunits in the rat hippocampus I: immunocytochemical
      distribution of 13 subunits.
AB  - The GABA(A) receptor is a ligand-operated chloride channel. It has a pentameric
      structure. In mammalian brain different subunits are recruited from four gene
      subfamilies. Using immunocytochemistry, we investigated the distribution of the
      13 GABA(A) receptor subunits in the hippocampus of the rat. GABA(A) receptor
      subunits were heterogeneously distributed within different hippocampal subfields.
      High concentrations of alpha1-, alpha2-, alpha4-, beta3-, gamma2- and delta
      immunoreactivities were observed within the molecular layer of the dentate gyrus,
      representing the dendritic area of the granule cells. In the hippocampus proper,
      the predominant GABA(A) receptor subunits were alpha1, alpha2, alpha5, beta3 and
      gamma2 that were located throughout the strata radiatum and oriens of CA1 to CA3.
      Immunocytochemical staining was there less prominent for alpha4-, beta1-, beta2-
      gamma3- and delta- subunits. In the hippocampus proper, the beta1 subunit was
      preferentially located in CA2. The alpha4- and delta-subunits were somewhat more
      abundant in CA1 than in CA3. Numerous local circuit neurons in the hippocampus
      proper and the hilus of the dentate gyrus contained alpha1-, beta2-, gamma2-
      and/or delta-subunits. Alpha3 and gamma1 were present only in minute amounts and
      no alpha6-IR was detected in the hippocampal formation. The distribution of the
      GABA(A) receptor subunits indicates the existence of heterogenously constituted
      GABA(A) receptor complexes within various hippocampal subfields, which may exert
      different physiological or pharmacological properties upon stimulation by GABA or
      its agonists.

PMID- 9284056
TI  - GABA(A) receptor subunits in the rat hippocampus II: altered distribution in
      kainic acid-induced temporal lobe epilepsy.
AB  - Intraperitoneal injection of kainic acid in the rat represents a widely used
      animal model of human temporal lobe epilepsy. Injection of kainic acid induces
      acute limbic seizures which are accompanied by seizure-induced brain damage and
      late spontaneous recurrent seizures. There is considerable evidence for an
      altered transmission of GABA in human temporal lobe epilepsy and in the kainic
      acid model. We therefore investigated by immunocytochemistry the distribution of
      13 GABA receptor subunits in the hippocampus of rats 12 h, 24 h, and two, seven
      and 30 days after injection of kainic acid. Within the molecular layer of the
      dentate gyrus, decreases in alpha2- and delta- and slight increases in alpha1,
      beta2- and beta3-immunoreactivities were observed at early intervals (12 to 24 h)
      after kainic acid injection. These changes were succeeded by marked increases in
      alpha1-, alpha2-, alpha4-, alpha5-, beta1-, beta3-, gamma2- and delta
      immunoreactivities in the same area after seven to 30 days. Within the
      hippocampus proper, changes in expression of GABA(A) receptor subunits were
      demarcated by considerable neurodegeneration of CA1 and CA3 pyramidal neurons.
      All subunits present within dendritic areas of CA1 and CA3 were affected. These
      were alpha1, alpha2, alpha5, beta1-beta3, gamma2 and alpha4 (present only in
      CA1). Decreases in these subunits were followed by increased expression of alpha2
      , alpha5-, beta3-, gamma2- and delta-subunits in the hippocampus proper notably
      in CA3 at later intervals (up to 30 days). Alpha1-, beta2-, gamma2- and delta
      subunits were found in presumed GABA containing interneurons throughout the
      hippocampus. Their immunoreactivity was augmented after two to seven days. Some
      alpha4-, gamma3- and delta-immunoreactivity was also found in astrocytes 48 h
      after kainic acid injection. Our data indicate an impairment of GABA-mediated
      neurotransmission due to a lasting loss of GABA(A) receptor containing cells
      after kainic acid-induced seizures. The seizure-induced loss in GABA(A) receptors
      within the hippocampus may in part be compensated by increased expression of
      GABA(A) receptor subunits within the molecular layer of the dentate gyrus and in
      pyramidal cells.

PMID- 9284057
TI  - GABA(A) receptor subunits in the rat hippocampus III: altered messenger RNA
      expression in kainic acid-induced epilepsy.
AB  - Kainic acid-induced seizures in rats represent an established animal model for
      human temporal lobe epilepsy. The neuropathological sequelae include acute status
      epilepticus followed by neurodegeneration in the CA1 and CA3 sector of the
      Ammon's horn and of interneurons in the hilus of the dentate gyrus. After about
      three weeks spontaneous recurrent seizures become manifest. We investigated
      changes in messenger RNA expression of 13 GABA(A) receptor subunits in the
      hippocampus of rats in the initial phase (6 h, 12 h and 24 h) after acute kainic
      acid-induced status epilepticus and seizure-related neuronal cell damage during
      and after acquisition of spontaneous recurrent seizures (seven and 30 days after
      kainic acid injection). In the granule cell layer, initial (after 6 to 12 h)
      decreases in (alpha2, alpha3, alpha5, beta1, beta3, gamma2 and delta messenger
      RNAs (by about 25 to 50%) were accompanied by increases (by about 50%) in alpha1,
      alpha4, and beta2 messages. At later intervals (after seven to 30 days),
      expression of alpha2, alpha4, beta3 and gamma2 messenger RNAs recovered to
      control values, with alpha5 and delta messenger RNA still being reduced (by 15
      and 40% below control levels, respectively). Concentrations of the transcripts
      encoding for alpha1, alpha3, beta1, beta2, became markedly enhanced (between 20
      and 50% of controls). Within the pyramidal cell layers CA1 and CA3, decreases in
      alpha2, alpha4, alpha5, beta(1-3) and gamma2 messenger RNAs were detected after
      seven to 30 days, reflecting pronounced neurodegeneration in these areas. The
      alpha1 transcript was decreased in CA3 after 24 h and increased to control levels
      indicating compensatory up-regulation of this message after seven days. Messenger
      RNAs encoding for alpha3-, gamma1-, and gamma3-subunits were detected at rather
      low levels, alpha6 was not present in the hippocampus. Our data suggest a fast
      but transient change in the expression of messenger RNAs encoding for different
      subunits of the GABA(A) receptor in the granule cell layer of the dentate gyrus.
      This is followed by a lasting augmentation of messenger RNAs encoding different
      GABA(A) receptor subunits in the same cell layer indicating long-lasting
      GABAergic inhibition. Changes within the pyramidal cell layer are mostly
      determined by concomitant neurodegenerative processes.

PMID- 9284058
TI  - Distribution and levels of [125I]IGF-I, [125I]IGF-II and [125I]insulin receptor
      binding sites in the hippocampus of aged memory-unimpaired and -impaired rats.
AB  - The insulin-like growth factors (IGF-I and IGF-II) and insulin are localized
      within distinct brain regions and their respective functions are mediated by
      specific membrane receptors. High densities of binding sites for these growth
      factors are discretely and differentially distributed throughout the brain, with
      prominent levels localized to the hippocampal formation. IGFs and insulin, in
      addition to their growth promoting actions, are considered to play important
      roles in the development and maintenance of normal cell functions throughout
      life. We compared the anatomical distribution and levels of IGF and insulin
      receptors in young (five month) and aged (25 month) memory-impaired and memory
      unimpaired male Long Evans rats as determined in the Morris water maze task in
      order to determine if alterations in IGF and insulin activity may be related to
      the emergence of cognitive deficits in the aged memory-impaired rat. In the
      hippocampus, [125I]IGF-I receptors are concentrated primarily in the dentate
      gyrus (DG) and the CA3 sub-field while high amounts of [125I]IGF-II binding sites
      are localized to the pyramidal cell layer, and the granular cell layer of the DG.
      [125I]insulin binding sites are mostly found in the molecular layer of the DG and
      the CA1 sub-field. No significant differences were found in [125I]IGF-I.
      [125I]IGF-II or [125I]insulin binding levels in any regions or laminae of the
      hippocampus of young vs aged rats. and deficits in cognitive performance did not
      relate to altered levels of these receptors in aged memory-impaired vs aged
      memory-unimpaired rats. Other regions. including various cortical areas, were
      also examined and failed to reveal any significant differences between the three
      groups studied. It thus appears that IGF-I, IGF-II and insulin receptor sites are
      not markedly altered during the normal ageing process in the Long Evans rat, in
      spite of significant learning deficits in a sub-group (memory-impaired) of aged
      animals. Hence. recently reported changes in IGF-I receptor messenger RNA levels
      in aged memory-impaired rats are apparently not reflected at the level of the
      translated protein.

PMID- 9284059
TI  - Systemic administration of kainic acid induces selective time dependent decrease
      in [125I]insulin-like growth factor I, [125I]insulin-like growth factor II and
      [125I]insulin receptor binding sites in adult rat hippocampal formation.
AB  - Administration of kainic acid evokes acute seizure in hippocampal pathways that
      results in a complex sequence of functional and structural alterations resembling
      human temporal lobe epilepsy. The structural alterations induced by kainic acid
      include selective loss of neurones in CA1-CA3 subfields and the hilar region of
      the dentate gyrus followed by sprouting and permanent reorganization of the
      synaptic connections of the mossy fibre pathways. Although the neuronal
      degeneration and process of reactive synaptogenesis have been extensively
      studied, at present little is known about means to prevent pathological
      conditions leading to kainate-induced cell death. In the present study, to
      address the role of insulin-like growth factors I and II, and insulin in neuronal
      survival as well as synaptic reorganization following kainate-induced seizure,
      the time course alterations of the corresponding receptors were evaluated.
      Additionally, using histological preparations, the temporal profile of neuronal
      degeneration and hypertrophy of resident astroglial cells were also studied.
      [125I]Insulin-like growth factor I binding was found to be decreased transiently
      in almost all regions of the hippocampal formation at 12 h following treatment
      with kainic acid. The dentate hilar region however, exhibited protracted
      decreases in [125I]insulin-like growth factor I receptor sites throughout (i.e.
      30 days) the study. [125I]Insulin-like growth factor II receptor binding sites in
      the hippocampal formation were found to be differentially altered following
      systemic administration of kainic acid. A significant decrease in [125I]insulin
      like growth factor II receptor sites was observed in CA1 subfield and the
      pyramidal cell layer of the Ammon's horn at all time points studied whereas the
      hilar region and the stratum radiatum did not exhibit alteration at any time. A
      kainate-induced decrease in [125I]insulin receptor binding was noted at all time
      points in the molecular layer of the dentate gyrus whereas binding in CA1-CA3
      subfields and discrete layers of the Ammon's horn was found to be affected only
      after 12 h of treatment. These results, when analysed with reference to the
      observed histological changes and established neurotrophic/protective roles of
      insulin-like growth factors and insulin, suggest possible involvement of these
      growth factors in the cascade of neurotrophic events that is associated with the
      reorganization of the hippocampal formation observed following kainate-induced
      seizures.

PMID- 9284061
TI  - Assessment of locomotor activity, acoustic and tactile startle, and prepulse
      inhibition of startle in inbred mouse strains and F1 hybrids: implications of
      genetic background for single gene and quantitative trait loci analyses.
AB  - As the use of transgenic and null mutation techniques in the development of
      animal models of disorders increases, the importance of selecting the appropriate
      genetic background also increases. The genetic background of the mouse strains
      used as models for various disorders is critical because of the potential for
      epistatic effects on the expression of transgenes and null mutations. Twelve
      strains of inbred mice and seven F1 hybrids were tested in multiple behavioural
      tasks including open-field locomotor activity, Y-maze activity, auditory and
      tactile startle and prepulse inhibition of startle response. Differences across
      genotypes were found for all variables measured. The range of variability among
      genotypes was dependent on the specific measure so careful consideration must be
      made in selecting a strain for testing a particular behaviour. Because of the
      polygenic nature of each of the behavioural phenotypes, the impact of a single
      gene manipulation may vary depending on the genetic background on which it is
      expressed. Moreover, quantitative trait loci methods could be applied to these
      behaviours.

PMID- 9284060
TI  - Potassium ion- and nitric oxide-induced exocytosis from populations of
      hippocampal synapses during synaptic maturation in vitro.
AB  - The development of mechanisms of neurotransmitter release is an important
      component in the formation of functional synaptic connections. Synaptic
      neurotransmitter release can be modulated by nitric oxide, a compound shown to
      have a variety of physiologic functions in the nervous system. The goal of this
      study was to determine whether, during synaptic maturation, nitric oxide is
      capable of affecting exocytosis of synaptic vesicles, and to compare its effects
      with those elicited by strongly depolarizing stimuli. To address these questions
      we examined vesicle release from large numbers of individual synapses of
      hippocampal neurons between five and 13 days in culture. Synaptic vesicles were
      labelled by uptake of the styrylpyridinium dye N-(3-triethylammoniumpropyl)-4-(4
      (dibutylamino)styryl)pyridinium dibromide (FM1-43) and their release was
      monitored by fluorescence imaging. Across populations of developing synapses,
      there was a good correspondence between FM1-43 staining and synapsin
      immunocytochemistry. A marked heterogeneity was observed in the ability to
      release vesicles both after potassium and nitric oxide stimulation. In less
      mature populations of synapses, the rate of potassium- and nitric oxide-induced
      exocytosis gradually increased, while at later stages nitric oxide-induced
      responses levelled off and potassium-induced responses continued to rise.
      Application of nitric oxide donors did not trigger any detectable changes in
      intracellular calcium. Combined immunocytochemical analysis of cultured
      hippocampal neurons for neuronal nitric oxide synthase and synapsin revealed that
      nitric oxide synthase was present within neurites of cultured hippocampal
      neurons, largely distributed in a bead-like pattern which partially overlapped
      presynaptic sites. Stimulation of the N-methyl-D-aspartate receptor while
      blocking propagation of action potentials with tetrodotoxin resulted in
      exocytosis from numerous individually resolved sites. Preincubation of neurons
      with an nitric oxide synthase inhibitor or addition of an nitric oxide scavenger
      eliminated these responses indicating a role for nitric oxide in N-methyl-D
      aspartate-stimulated exocytosis. Using fluorescence imaging of individually
      resolved synaptic sites, we provide direct evidence for an effect of nitric oxide
      on vesicular neurotransmitter release in intact neurons. Nitric oxide is capable
      to produce this effect at all stages of synaptic development and acts
      independently of calcium influx. We show that nitric oxide synthase is present at
      synaptic sites and endogenously produced nitric oxide is sufficient to cause
      exocytosis. Taken together, these experiments suggest a possible role for nitric
      oxide in calcium-independent transmitter release in populations of synapses at
      all stages of maturation.

PMID- 9284062
TI  - Assessment of learning by the Morris water task and fear conditioning in inbred
      mouse strains and F1 hybrids: implications of genetic background for single gene
      mutations and quantitative trait loci analyses.
AB  - Genetic methods including the creation of transgenic or null mutant models and
      mapping studies using quantitative trait loci strategies can be used to identify
      candidate genes in mice that regulate learning processes. Interpretations as to
      the impact of single gene mutations for polygenic behaviours like learning will
      depend in part on the genetic background of the animals used for these
      manipulations. To address the issue of genetic variability, 12 inbred strains and
      seven different F1 hybrids were tested on multiple behavioural tasks, including
      two complex learning paradigms: the Morris water task and fear conditioning.
      Strain differences were found for all variables measured. In the hidden platform
      version of the Morris task, the albino animals performed poorly while overall the
      F1 hybrids showed the best selectivity for the trained quadrant as measured in a
      probe trial. In contrast, almost all genotypes performed well on the contextual
      fear conditioning task and learned to associate the test context with the pairing
      of a foot shock and auditory stimulus as demonstrated 24 h after training by
      increased freezing in the test environment compared to an altered context.
      Significant genetic correlations were obtained for behavioural measures
      suggesting that the same genes regulate various aspects of performance on
      behavioural tasks. Scores from these multiple inbred strains and F1 hybrids
      provide a baseline level of learning ability for fear conditioning and the Morris
      water task. The results of the present study confirm the importance of genetic
      background in the performance of various learning tasks. This variability should
      be considered when developing new transgenic or null mutant animal models.

PMID- 9284063
TI  - Shortened-duration GABA(A) receptor-mediated synaptic potentials underlie
      enhanced CA1 excitability in a chronic model of temporal lobe epilepsy.
AB  - Intracellular recording techniques were used to examine GABA(A) receptor-mediated
      synaptic inhibition in pyramidal cells of the CA1 region of the rat hippocampus
      in the post-self sustaining limbic status epilepticus model of temporal lobe
      epilepsy. Orthodromically evoked, monosynaptic inhibitory postsynaptic potentials
      were recorded in vitro following pharmacological blockade of ionotropic glutamate
      and GABA(B) receptors. Inhibitory postsynaptic potentials from epileptic tissue
      were kinetically altered relative to controls; both the 10-90% rise-time and
      width (measured at half-maximum amplitude) were reduced by approximately 50%
      resulting in significant shortening of duration. The degree of pyramidal cell
      hyperexcitability, assessed before pharmacological treatment as the number of
      action potentials evoked by maximum intensity afferent stimulation, correlated
      significantly with the magnitude of synaptic potential duration reduction
      determined following blockade of glutamatergic neurotransmission. Bath
      application of the benzodiazepine type 1 receptor agonist zolpidem reduced post
      self sustaining limbic status epilepticus CA1 pyramidal cell hyperexcitability
      substantially (but not completely) via a marked increase in inhibitory
      postsynaptic potential area. Post-self-sustaining limbic status epilepticus
      inhibitory postsynaptic potentials which exhibited the most pronounced shortening
      were augmented by zolpidem to a greater degree than longer duration synaptic
      potentials. In contrast, zolpidem-induced augmentation of control inhibitor,
      postsynaptic potential area was much less robust. It is suggested that a
      deficiency in post-self-sustaining limbic status epilepticus GABA(A) receptor
      mediated synaptic inhibition contributes to a state of partial disinhibition
      which is a major factor in enhanced CA1 excitability in chronic limbic epilepsy.
      Possible mechanisms underlying post-self-sustaining limbic status epilepticus
      kinetic abnormalities are discussed.

PMID- 9284064
TI  - Parvalbumin-immunoreactive neurons in the hippocampal formation of Alzheimer's
      diseased brain.
AB  - The number and topographic distribution of immunocytochemically stained
      parvalbumin interneurons was determined in the hippocampal formation of control
      and Alzheimer's diseased brain. In control hippocampus, parvalbumin interneurons
      were aspiny and pleomorphic, with extensive dendritic arbors. In dentate gyrus,
      parvalbumin cells, as well as a dense plexus of fibers and puncta, were
      associated with the granule cell layer. A few cells also occupied the molecular
      layer. In strata oriens and pyramidale of CA1-CA3 subfields, parvalbumin neurons
      gave rise to dendrites that extended into adjacent strata. Densely stained puncta
      and beaded fibers occupied stratum pyramidale, with less dense staining in
      adjacent strata oriens and radiatum. Virtually no parvalbumin profiles were
      observed in stratum lacunosum-moleculare or the alveus. Numerous polymorphic
      parvalbumin neurons and a dense plexus of fibers and puncta characterized the
      deep layer of the subiculum and the lamina principalis externa of the
      presubiculum. In Alzheimer's diseased hippocampus, there was an approximate 60%
      decrease in the number of parvalbumin interneurons in the dentate gyrus/CA4
      subfield (P<0.01) and subfields CA1-CA2 (P<0.01). In contrast, parvalbumin
      neurons did not statistically decline in subfields CA3, subiculum or presubiculum
      in Alzheimer's diseased brains relative to controls. Concurrent staining with
      Thioflavin-S histochemistry did not reveal degenerative changes within
      parvalbumin-stained profiles. These findings reveal that parvalbumin interneurons
      within specific hippocampal subfields are selectively vulnerable in Alzheimer's
      disease. This vulnerability may be related to their differential connectivity,
      e.g., those regions connectionally related to the cerebral cortex (dentate gyrus
      and CA1) are more vulnerable than those regions connectionally related to
      subcortical loci (subiculum and presubiculum).

PMID- 9284065
TI  - Sprouting and functional recovery in co-cultures between old and young
      hippocampal organotypic slices.
AB  - We developed a model of lesion of Schaffer collaterals in hippocampal organotypic
      slice cultures to analyse the capacity for sprouting and functional recovery
      expressed in young (one week old) and old (four week old) slice cultures. Slice
      cultures were sectioned at different ages of maturation in two separate half
      slices and maintained in co-culture. Functional recovery was assessed by
      measuring synaptic responses elicited across the lesion seven days after the
      lesion and sprouting was evaluated by biocytin labeling of the regenerating
      fibers seen under the same conditions. Sprouting and functional recovery were
      found to be markedly reduced and delayed in old vs young cultures. Preparation of
      co-cultures between young CA3 and old CA1 half-slices resulted in a significant
      reduction in the capacity for sprouting and regeneration of the young CA3
      neurons. Conversely, co-cultures prepared between old CA3 and young CA1 half
      slices showed a markedly enhanced capacity for sprouting and functional recovery
      of old CA3 neurons. These results indicate that the age-dependent impairment in
      sprouting and regeneration expressed in cortical regions can be improved by and
      depends upon the presence of a favourable environment.

PMID- 9284066
TI  - Lactation-induced plasticity in the supraoptic nucleus augments axodendritic and
      axosomatic GABAergic and glutamatergic synapses: an ultrastructural analysis
      using the disector method.
AB  - The disector, an unbiased stereological method for evaluation of synaptic
      densities, was used to analyse putative GABA and glutamate innervations of the
      supraoptic nucleus of virgin and lactating rats. The analysis was performed on
      ultrathin sections labelled for either of the amino acids with a postembedding
      immunogold technique. Our observations showed that the volume of the nucleus
      increased by 40% in lactating animals, an increase due to a significant
      enlargement of dendritic and somatic, but not vascular, volumes. Nevertheless,
      values of overall synaptic densities in the whole nucleus remained as high as
      those in virgin rats (37-40 x l0(6) synapses/mm3). About 45% of all synapses were
      immunoreactive for GABA and 25% for glutamate; there were twice as many GABA- and
      glutamate-positive synapses on dendrites as on somata. When we estimated synaptic
      densities in relation to the neuropil (by subtracting the proportion of sampled
      areas occupied by somatic profiles), we found a significant increase in synaptic
      density in lactating animals. This affected axodendritic as well as axosomatic
      synapses, immunopositive and immunonegative for GABA or glutamate. The disector
      also allowed us to determine that the number of synapses from terminals making
      contacts on several somata and/or dendrites simultaneously constituted about 9%
      of all synapses in virgin rats, a proportion which more than doubled in lactating
      rats. About 50% were immunopositive for GABA and 30% for glutamate. Our data
      offer further evidence of physiologically-linked structural synaptic plasticity
      in the supraoptic nucleus and clearly demonstrate that it affects both inhibitory
      and excitatory inputs on dendrites, as well as on somata, throughout the nucleus.

PMID- 9284067
TI  - Peripubertal refinement of the intrinsic and associational circuitry in monkey
      prefrontal cortex.
AB  - The peripubertal elimination of axospinous synapses and dendritic spines in
      monkey prefrontal cortex suggests that this region undergoes substantial
      reorganization during late postnatal development. Understanding the functional
      impact of these maturational refinements requires knowledge of the specific
      presynaptic elements involved in these changes. Two potential sources of these
      presynaptic terminals are the intrinsic axon collaterals furnished by pyramidal
      cells within a region and the associational axons that arise from pyramidal
      neurons in other cortical regions in the same hemisphere. In the adult, both of
      these types of axon terminals form synapses predominantly with dendritic spines
      on other pyramidal neurons, and thus they may be preferentially involved in the
      peripubertal pruning of axospinous synapses and dendritic spines. In order to
      test this hypothesis, iontophoretic injections of the anterograde tracer
      biotinylated dextran amine were made into the superficial layers of areas 9 or 46
      of the prefrontal cortex of four prepubertal juvenile (14.9-21.5 months old) and
      three young adult macaque monkeys. Tangential reconstructions revealed a stripe
      like pattern of labeled terminals for intrinsic and associational projections in
      both juvenile and adult animals. During puberty, the intrinsic circuitry
      underwent extensive topographic refinement, as demonstrated by a 42.7% decrease
      in stripe area and a 28.0% increase in gap distance between stripes. Furthermore,
      the mediolateral tangential spread of labeled stripes around the injection site
      decreased by 27.0%. In contrast, topographic refinement was not evident in the
      associational circuitry. In both layers 1 and 3, the densities of varicosities
      and branch points on labeled axons decreased by about 50% in intrinsic stripes
      during puberty, but only by approximately 30% in associational stripes. These
      findings suggest that the spatial form and magnitude of peripubertal refinements
      in prefrontal cortical connectivity may be specific for certain neural elements.

PMID- 9284068
TI  - Effects of cholinergic depletion on experience-dependent plasticity in the cortex
      of the rat.
AB  - Clinical and functional studies have strongly suggested that acetylcholine input
      from the nucleus basalis of Meynert is important for the cortex's adaptive
      response to experience. The purpose of this study was to investigate the effects
      of depletion of acetylcholine inputs from nucleus basalis of Meynert on
      experience-dependent plasticity in the cortex of young adult male rats. The
      posteromedial barrel subfield in the primary somatosensory cortex was studied.
      Experience-dependent plasticity was elicited using a whisker-pairing paradigm in
      which all whiskers except D2 and D3 were trimmed daily. Plasticity within barrel
      D2 of the posteromedial barrel subfield was measured using the
      electrophysiological extracellular recording technique. An index of plasticity
      was determined in two ways: as an increase in the magnitude of evoked activity to
      stimulation of whisker D2 and as a bias in the ratio of evoked activity for
      stimulation of paired whisker D3 and cut whisker D1 (D3/D1). Whiskers D2, D3 and
      D1 were stimulated (deflected) by a Chubbuck electromechanical stimulator.
      Cholinergic neurons in the nucleus basalis of Meynert were selectively lesioned
      with an immunotoxin, 192 IgG-saporin, injected into the left lateral ventricle.
      Lesions of cholinergic neurons in the nucleus basalis of Meynert were verified
      using choline acetyltransferase immunocytochemistry and radioenzymatic assay.
      Experience-dependent plasticity was significantly reduced in cholinergic-depleted
      animals. The magnitude of evoked activity to stimulation of whisker D2 increased
      by 16-100% in control animals compared with 0-20% in cholinergic-depleted
      animals. Similarly, compared to a 60-100% increase in the D3/D1 ratio of evoked
      activity for phosphate-buffered saline-injected control animals, cholinergic
      depleted rats showed no significant increase in the D3/D1 ratio (0-15%) after
      undergoing the whisker-pairing paradigm. After whisker trimming, the D3/D1
      response ratio in immunotoxin-treated animals was essentially the same as in
      control animals that had not been subjected to the whisker-pairing paradigm. This
      study showed that no significant plasticity response was observed in the absence
      of cholinergic input from the nucleus basalis of Meynert. The mechanisms of the
      action of acetylcholine in cortical plasticity are still not known, but we
      hypothesize that this type of plasticity is activity dependent and is
      significantly enhanced in the presence of acetylcholine.

PMID- 9284070
TI  - Distribution and postnatal ontogeny of adenosine A2A receptors in rat brain:
      comparison with dopamine receptors.
AB  - In adult rat brain, adenosine A2A receptors and dopamine D2 receptors are known
      to be located on the same cells where they interact in an antagonistic manner. In
      the present study we wanted to examine when this situation develops and compared
      the postnatal ontogeny of the binding of the adenosine A2A receptor agonist
      [3H]CGS 21680, the binding of the dopamine D1 receptor antagonist [3H]SCH 23390
      and the dopamine D2 receptor antagonist [3H]raclopride. All three radioligands
      bound to the striatum at birth and this binding increased several-fold during the
      postnatal period. [3H]SCH 23390 binding developed first (mostly during the first
      week), followed by [3H]raclopride binding (first to third week) and [3H]CGS 21680
      binding (only during second and third week). For all three radioligands the
      binding tended to decrease between 21 days and adulthood. This occurred earlier
      and was more pronounced in the globus pallidus than in the other examined
      structures. The increase in [3H]CGS 21680 binding from newborn to adult was
      mainly due to four-fold increase in the number of binding sites. The pharmacology
      of [3H]CGS 21680 binding to caudate-putamen was similar in newborn, one-week-old
      and adult animals, and was indicative of A2A receptors. The binding was inhibited
      by guanylyl imidodiphosphate at all ages, indicating that A2A receptors are G
      protein-coupled already at birth. In contrast to the large increase in [3H]CGS
      21680 binding, there was a decrease in the levels of A2A messenger RNA during the
      postnatal period in the caudate-putamen. In cerebral cortex [3H]CGS 21680 bound
      to a different site than the A2A receptor. From birth to adulthood cortical
      binding of [3H]CGS 21680 increased four-fold and that of the adenosine A1 agonist
      [3H]cyclohexyladenosine 19-fold. During early postnatal development [3H]SCH 23390
      binding was higher in deep than in superficial cortical layers, but this
      difference disappeared in adult animals. There was binding of both [3H]CGS 21680
      and [3H]cyclohexyladenosine to the olfactory bulb, suggesting a role of the two
      adenosine receptors in processing of olfactory information. [3H]CGS 21680 binding
      was present in the external plexiform layer and glomerular layer, and increased
      during development, but the density of binding sites was about one tenth of that
      seen in caudate putamen. [3H]cyclohexyladenosine showed a very different
      labelling pattern, resembling that observed with [3H]SCH 23390. Postnatal changes
      in adenosine receptors may explain age-dependent differences in stimulatory
      caffeine effects and endogenous protection against seizures. Since A2A receptors
      show a co-distribution with D2 receptors throughout development, caffeine may
      partly exert such actions by regulating the activity of D2 receptor-containing
      striatopallidal neurons.

PMID- 9284069
TI  - Cellular expression of adenosine A2A receptor messenger RNA in the rat central
      nervous system with special reference to dopamine innervated areas.
AB  - The cellular distribution of adenosine A2A receptor messenger RNA in the central
      nervous system was investigated using in situ hybridization with ribonucleotide
      probes. A specific expression was found in the dorsal (i.e. caudate putamen) and
      ventral (i.e. nucleus accumbens and olfactory tubercle) striatum, the lateral
      septum and in some cerebellar Purkinje cells. Simultaneous detection of
      radioactive and non-radioactive probes showed that the majority of adenosine A2A
      receptor messenger RNA-containing neurons in the dorsal and ventral striatum co
      expressed dopamine D2 receptor messenger RNA and preproenkephalin A messenger
      RNA. However, a minor sub-population of neurons expressing adenosine A2A receptor
      messenger RNA, but not preproenkephalin A messenger RNA, was found in clusters
      along the ventral border of the nucleus accumbens. Only a small number of
      striatal neurons expressing dopamine D1 receptor or substance P messenger RNAs
      also expressed adenosine A2A receptor messenger RNA. Finally, in the ventral part
      of nucleus accumbens and in the olfactory tubercle a major sub-population of
      neurons expressed preproenkephalin A messenger RNA, but not adenosine A2A
      receptor messenger RNA. Cholinergic interneurons did not express adenosine A2A
      receptor messenger RNA. Thus, the extensive co-localization of adenosine A2A and
      dopamine D2 receptors previously described in the dorsal striatum extends into
      its ventral part. There is also a high degree of co-expression of adenosine A2A
      receptor messenger RNA and preproenkephalin A messenger RNA in the ventral
      striatum, but within this region several topologically defined sub-populations of
      neurons express only one of these transcripts. A majority of the adenosine A2A
      receptor messenger RNA-containing neurons in the lateral septum did contain
      preproenkephalin A messenger RNA, whereas only a few co-expressed dopamine D2
      receptor messenger RNA. This detailed investigation demonstrates that most of the
      subcortical areas innervated by dopamine have an abundant, although restricted
      expression of the adenosine A2A receptor gene and that this receptor is expressed
      in very few cells outside these areas. These results predict that adenosine A2A
      receptors are involved not only in motor behaviour, but also in goal-oriented
      behaviours.

PMID- 9284071
TI  - Hypoxia-induced Fos expression in neurons projecting to the pressor region in the
      rostral ventrolateral medulla.
AB  - Previous studies in anaesthetized animals have shown that the hypoxia-induced
      increase in sympathetic vasomotor activity is largely dependent on synaptic
      excitation of sympathoexcitatory pressor neurons in the rostral part of the
      ventrolateral medulla. The primary aim of this study was to determine, in
      conscious rabbits, the distribution of neurons within the brain that have
      properties characteristic of interneurons conveying excitatory inputs to the
      rostral ventrolateral medullary pressor region in response to systemic hypoxia.
      In a preliminary operation, a retrogradely-transported tracer, fluorescent
      labelled microspheres, was injected into the physiologically-identified pressor
      region in the rostral ventrolateral medulla. After a waiting period of one to two
      weeks, the conscious rabbits were subjected to moderate hypoxia (induced by
      breathing 10% O2 in N2) for a period of 60 min. Control groups of animals were
      exposed to room air or to mild hypoxia (12% O2 in N2). Moderate hypoxia resulted
      in a modest hypertension of approximately 15 mmHg, and in the expression of Fos
      (a marker of neuronal activation) in many neurons in the nucleus tractus
      solitarius, the rostral, intermediate and caudal parts of the ventrolateral
      medulla, the Kolliker-Fuse nucleus, locus coeruleus, subcoeruleus and A5 area in
      the pons as well as in several midbrain and forebrain regions, including the
      periaqueductal grey in the midbrain and the paraventricular, supraoptic and
      arcuate nuclei in the hypothalamus. Fos expression was also observed in these
      regions in rabbits subjected to mild hypoxia or normoxia, but it was much reduced
      compared to rabbits subjected to moderate hypoxia. Approximately half of the
      neurons in the ventrolateral medulla, 27% of neurons in the nucleus tractus
      solitarius, and 49-81% of neurons in the locus coeruleus, sub-coeruleus and A5
      area that expressed Fos following moderate hypoxia were also immunoreactive for
      tyrosine hydroxylase, and were therefore catecholamine cells. Approximately half
      of the neurons in the nucleus tractus solitarius and two-thirds of neurons in the
      Kolliker-Fuse nucleus that expressed Fos following moderate hypoxia were
      retrogradely labelled from the rostral ventrolateral medullary pressor region.
      Similarly, approximately one quarter of Fos-positive cells in the caudal and
      intermediate ventrolateral medulla were retrogradely labelled, but very few Fos
      positive/retrogradely-labelled cells were found in other pontomedullary or
      suprapontine brain regions. The results indicate that systemic hypoxia results in
      activation of neurons in several discrete nuclei in the brainstem and forebrain,
      including neurons in all the major pontomedullary catecholamine cell groups.
      However, neurons that are activated by systemic hypoxia and that also project to
      the rostral ventrolateral medullary pressor region are virtually confined to the
      lower brainstem, primarily in the nucleus tractus solitarius and Kolliker-Fuse
      nucleus and to a lesser extent the caudal/intermediate ventrolateral medulla. In
      a previous study from our laboratory, we determined the distribution of neurons
      in the brainstem that are activated by hypertension and that also project to the
      rostral ventrolateral medullary pressor region. [Polson et al. (1995)
      Neuroscience 67, 107-123]. Comparison of the present results with those from this
      previous study indicates that the hypoxia-activated neurons in the nucleus
      tractus solitarius and Kolliker-Fuse nucleus that project to the rostral
      ventrolateral medulla are likely to be interneurons conveying excitatory
      chemoreceptor signals, while those in the caudal/intermediate ventrolateral
      medulla are likely to be mainly interneurons conveying inhibitory baroreceptor
      signals, activated by the rise in arterial blood pressure associated with the
      hypoxia-induced hypertension.

PMID- 9284072
TI  - Glutamate- and GABA-immunoreactive synapses on sympathetic preganglionic neurons
      caudal to a spinal cord transection in rats.
AB  - Spinal cord injury destroys bulbospinal amino acid-containing pathways to
      sympathetic preganglionic neurons and severely disrupts blood pressure control,
      resulting in resting or postural hypotension and episodic hypertension. Almost
      all immunoreactivity for the excitatory amino acid L-glutamate has been reported
      to disappear from autonomic areas of the cord caudal to a transection, apparently
      depriving autonomic neurons of their major excitatory input. However, the
      magnitude of the neurogenic episodic hypertension after cord injury suggests that
      excitatory inputs to sympathetic preganglionic neurons must still be present.
      Moreover, the hypotension associated with high spinal injuries may reflect a
      enhanced role for inhibitory transmitters, such as GABA. This apparent
      contradiction regarding the presence of glutamate and lack of information about
      GABA prompted the present investigation. In rats seven days after spinal cord
      transection, we examined identified sympathetic preganglionic neurons caudal to
      the injury for the presence of synapses or direct contacts from varicosities that
      were immunoreactive for the amino acids, L-glutamate and GABA. Adrenal
      sympathetic preganglionic neurons were retrogradely labelled with cholera toxin B
      subunit and amino acid immunoreactivity was revealed with post-embedding
      immunogold labelling. In single ultrathin sections, 46% (98/212) of the synapses
      or direct contacts on adrenal sympathetic preganglionic neurons were
      immunoreactive for glutamate and 39% (83/214) were immunoreactive for GABA.
      Analysis of inputs with the physical disector yielded similar results for the two
      amino acids. The proportions of glutamatergic or GABAergic synapses on cell
      bodies and dendrites were similar. When alternate ultrathin sections were stained
      to reveal glutamate or GABA immunoreactivity, either one or the other amino acid
      occurred in 78.4% (116/148) of inputs; 4.1% (6/148) of inputs contained both
      amino acids and 17.5% (26/148) of inputs contained neither. These results
      demonstrate that nerve fibres immunoreactive for the neurotransmitter amino
      acids, glutamate and GABA, provide most of the input to sympathetic preganglionic
      neurons caudal to a spinal cord transection. Synapses containing glutamate and
      GABA could provide the anatomical substrate for the exaggerated sympathetic
      reflexes and the low sympathetic tone that result from spinal cord injury.

PMID- 9284074
TI  - Localization of proteins associated with the outer hair cell plasma membrane in
      the gerbil cochlea.
AB  - There is substantial evidence that the motility of mammalian outer hair cells is
      generated close to or within the plasma membrane. Several analogies between the
      outer hair cell cortical lattice and the membrane-related cytoskeleton of
      erythrocytes have been noted. In erythrocytes a member of the anion exchanger
      protein family, AE1, also known as Band 3, is involved in membrane-cytoskeleton
      linkage via Protein 4.1. In the following paper, the presence of these two
      proteins in gerbilline outer hair cells is confirmed by western blot.
      Furthermore, co-localization of these two proteins was detected in the lateral
      wall of outer hair cells by immunofluorescence and postembedding electron
      immunohistochemistry. Band 3 is restricted to this region, whereas Protein 4.1
      has a somewhat more dispersed distribution. Thus, the structure of these sensory
      receptor cells may result from an adaptation of a strategy used by other motile
      cells. The proteins investigated likely have a support function and may comprise
      "pillars" seen between the lateral plasma membrane and the cytoskeleton in
      micrographs of outer hair cells. The possibility that Band 3 comprises "protein
      particles" seen in the lateral plasma membrane, or maybe directly involved in the
      voltage-dependent force generation in outer hair cells, is also discussed.

PMID- 9284073
TI  - Mast cell number and maturation in the central nervous system: influence of
      tissue type, location and exposure to steroid hormones.
AB  - While it is well established that brain mast cells are usually associated with
      the cerebral vasculature, in ring doves mast cells lie directly in the neuropil
      of the medial habenula. During normal development mast cells enter the habenula
      and complete their differentiation in situ. In the present study, we asked what
      characteristics of the medial habenula contribute to mast cell entry and
      differentiation. Grafts of embryonic habenula or control optic tectal grafts were
      placed in the lateral ventricle or anterior chamber of the eye. Transplantation
      alters the location of the habenula as well as its neural and vascular
      connections. Three groups of hosts were used for the ventricular grafts: four
      month-old and killed three months after transplantation; four-month-old and
      killed seven months later, and two- to three-year-old gonadectomized males killed
      three months later. Hosts for the intraocular grafts were four months of age and
      killed three months later. Mast cells were present in the habenular grafts but
      not in the control tissue. Mast cells in three- and seven-month-old grafts were
      phenotypically immature when compared to those of hosts. They contained fewer
      metachromatic granules, fewer granules immunoreactive to an antiserum against
      gonadotropin-releasing hormone, and no highly-sulphated proteoglycans. As
      previously described, gonadectomized adults had fewer mast cells in their medial
      habenula than did intact animals, but there was no change in mast cell number in
      habenular grafts. The current experiments indicate that the occurrence and
      survival of mast cells can occur within the microenvironment of the medial
      habenula, but that maturation of these cells requires the normal connections of
      this nucleus. Furthermore, gonadectomy appears to alter mast cell number in the
      medial habenula by generating a secondary signal which the transplanted tissue is
      incapable of receiving or processing.

PMID- 9284075
TI  - Motor and cognitive deficits in apolipoprotein E-deficient mice after closed head
      injury.
AB  - Previous studies suggest that traumatic brain injury is associated with increased
      risk factor for developing Alzheimer's disease. Furthermore, the extent of the
      risk seems to be most pronounced in Alzheimer's disease patients who carry the
      epsilon4 allele of apolipoprotein E, suggesting a connection between
      susceptibility to head trauma and the apolipoprotein E genotype. Apolipoprotein E
      deficient mice provide a useful model for investigating the role of this
      lipoprotein in neuronal maintenance and repair. In the present study
      apolipoprotein E-deficient mice and a closed head injury experimental paradigm
      were used to examine the role of apolipoprotein E in brain susceptibility to head
      trauma and in neuronal repair. Apolipoprotein E-deficient mice were assessed up
      to 40 days after closed head injury for neurological and cognitive functions, as
      well as for histopathological changes in the hippocampus. A neurological severity
      score used for clinical assessment revealed more severe motor and behavioural
      deficits in the apolipoprotein E-deficient mice than in the controls, the
      impairment persisting for at least 40 days after injury. Performance in the
      Morris water maze, which tests spatial memory, showed a marked learning deficit
      of the apolipoprotein E-deficient mice when compared with injured controls, which
      was apparent for at least 40 days. At this time, histopathological examination
      revealed overt neuronal cell death bilaterally in the hippocampus of the injured
      apolipoprotein E-deficient mice. The finding that apolipoprotein E-deficient mice
      exhibit an impaired ability to recover from closed head injury suggests that
      apolipoprotein E plays an important role in neuronal repair following injury and
      highlights the applicability of this mouse model to the study of the cellular and
      molecular mechanisms involved.

PMID- 9284077
TI  - Blood microdialysis in humans: a new method for monitoring plasma compounds.
AB  - A new venous microdialysis probe for humans was developed. The active area was
      made with cellulose membrane (220 mm outside diameter, length 20 mm, and 6000
      molecular weight cut off). Glucose measurements were used to test it. The
      relative recovery was 50% in dialysates obtained in vitro, the step response was
      91.8% in the first 2 min. The in vivo recovery was 65.8% obtained by the no net
      flux method, with the probe placed in the cubital vein of the subjects arms.
      Corrected glucose in dialysates was non significantly different from plasma
      glucose simultaneously collected. In healthy male volunteers from 18 to 37 years
      of age, mean 22.1 years, the glucose levels in the blood dialysates were measured
      every 30 min, 60 min before and 150 min after an oral load of 75 g of glucose or
      vehicle. Glucose increased significantly after the load. The differences with the
      control group were significant at 60 and 90 min after the treatment. The results
      showed the easy and safe application of this technique to monitor endogenous and
      exogenous compounds in the extracellular compartment of blood in out patients.

PMID- 9284076
TI  - Both iso- and hyperosmotic ethanol stimulate release of hypothalamic thyrotropin
      releasing hormone despite opposite effect on neuron volume.
AB  - Previous studies have indicated that isosmolar, but not hyperosmolar, ethanol
      induces in vitro gonadotropin-releasing hormone secretion from the basal
      hypothalamus, presumably by causing cell swelling. Moreover, ethanol reduces
      secretion of another hypothalamic neuropeptide vasopressin. We have studied the
      acute effect of ethanol on specific hypophysiotropic basal and K+-stimulated
      thyrotropin-releasing hormone secretion in vitro especially in relation to cell
      swelling. Isosmotic 40-160 mM ethanol increased thyrotropin-releasing hormone
      release from the hypothalamic paraventricular nucleus and median eminence in a
      dose-dependent manner. Both a 30% decrease of osmolarity and isosmotic 80 mM
      ethanol induced 12% swelling of hypothalamic neurons. Hyperosmotic 80 mM or 160
      mM ethanol induced release of thyrotropin-releasing hormone from both
      hypothalamic structures but did not cause cell swelling (80 mM) or even induced
      cell shrinkage (160 mM). Depletion of medium Ca2+ did not affect thyrotropin
      releasing hormone secretion caused by either isosmotic or hyperosmotic ethanol.
      Our data indicate that both iso- and hyperosmotic ethanol stimulated release of
      hypophysiotropic thyrotropin-releasing hormone despite opposite effects on neuron
      volume. The mechanism of ethanol action appears complex and variable depending on
      the type of cell and neuropeptide affected.

PMID- 9284079
TI  - Effect of estradiol metabolites on the susceptibility of low density lipoprotein
      to oxidation.
AB  - The main estradiol metabolites 2-hydroxyestrone, 2-methoxyestrone and 16alpha
      hydroxyestrone were investigated in vitro for the susceptibility of low density
      lipoprotein to oxidation and the effects compared with those of estradiol and
      vitamin E. 2-hydroxyestrone and 2-methoxyestrone had a greater inhibitory effect
      than estradiol and vitamin E whereas 16alpha-hydroxyestrone approximates the
      inhibition of estradiol. These results indicate that 2-hydroxyestrone and 2
      methoxyestrone possess non-genomic actions which may play a role in the lipid
      metabolism.

PMID- 9284078
TI  - Long-term melatonin supplementation does not recover the impairment of natural
      killer cell activity and lymphocyte proliferation in aging mice.
AB  - In this study we evaluated the effect of long-term melatonin (MEL) treatment on
      the cytotoxic activity and number of natural killer (NK) cells and the
      proliferative response of spleen lymphocytes to phytohemagglutinin (PHA) or
      interleukin-2 (IL-2) in old mice. Seventeen-eighteen month-old Balb/c mice were
      supplemented with MEL (40-50 microg/day/mouse) and sacrificed after eight months.
      The MEL supplementation was unable to recover the low levels of both endogenous
      and IL-2-induced NK cell activity found in old untreated mice. Also the NK cell
      number was unaffected by MEL treatment. The spleen lymphocyte proliferative
      response to both PHA and IL-2 was not different in old MEL-treated compared to
      old untreated mice. These results indicate that long-term MEL supplementation
      does not recover the age-related deterioration of NK cell activity and lymphocyte
      proliferative capacity.

PMID- 9284080
TI  - Effect of Rp diastereoisomer of adenosine 3',5' cyclic-monophosphothioate on the
      cAMP-dependent relaxation of smooth muscle.
AB  - The effect of Rp diastereoisomer of adenosine 3',5'-cyclic monophosphothioate (Rp
      cAMPS) on relaxation elicited by histamine (1-100 microM), forskolin (1-60
      microM), papaverine (1-100 microM), vinpocetine (1-100 microM), rolipram (0.1-1
      mM), Sp-cAMPS (10-300 microM), 8-BrcAMP (10 microM - 1 mM) and 8-BrcGMP (3 microM
      - 1 mM) of the previous vanadate-induced contraction was assayed. The effect of
      Rp-cAMPS on the relaxing effect produced by forskolin, papaverine, vinpocetine,
      rolipram, Sp-cAMPS and 8-BrcAMP in KCl-induced tonic contraction was also
      assayed. Histamine, forskolin, papaverine, rolipram, Sp-cAMPS, 8-BrcAMP and 8
      BrcGMP, but not vinpocetine, relaxed the vanadate-induced contractions in rat
      uterus incubated in medium lacking calcium plus EDTA in a concentration-dependent
      way. Rp-cAMPS (1-300 microM) had no effect on vanadate contraction. However, it
      antagonized the relaxation elicited by histamine and papaverine, but not that of
      forskolin, rolipram, Sp-cAMPS, 8-BrcAMP and 8-BrcGMP. Forskolin, papaverine,
      vinpocetine, rolipram and 8-BrcAMP, but not Sp-cAMPS, relaxed the KCl-induced
      contraction. Rp-cAMPS antagonized the relaxation elicited by forskolin,
      papaverine and vinpocetine, but not that of rolipram and 8-BrcAMP. Our results
      suggest that: a) Rp-cAMPS is an effective PKA inhibitor that could be used to
      study the involvement of cAMP on drug-induced response in smooth muscle, and b)
      the effects of Sp-cAMPS, 8-BrcAMP and rolipram were independent of the activation
      of protein kinases.

PMID- 9284081
TI  - Hypothalamo-pituitary-IGF-1 axis in female rats made obese by overfeeding.
AB  - A gender-related impairment of the somatotrophic axis is present in obese Zucker
      rats, female rats being better preserved than males. We showed that another
      animal model of obesity, i.e., male rats made obese by feeding a hypercaloric
      diet had a reduced function of somatotrophic axis which was likely related to
      impairment of gonadal function. Aim of this work was that of studying the
      function of somatotrophic axis in female overfed rats and comparing it to that of
      male rats of the previous study. Sprague-Dawley female rats were fed an energy
      rich palatable diet for seven months. At the end of overfeeding, according to the
      degree of overweight, rats were divided into overtly obese (Obese), overweight
      (Overweight) and Non-Obese, i.e. rats whose weights were similar to those of
      controls. Rats fed ad libitum with the standard pellet chow served as controls
      (Controls). Acute administration of a supramaximal dose of GHRH (2 microg/rat,
      iv) elicited a plasma GH rise similar to that of Controls in all the groups,
      except in Obese which had a lower GH response. Growth hormone responses after
      GHRH administration were inversely related to plasma levels of free fatty acids
      (FFA). Pituitary GH content and gene expression as well as hypothalamic GHRH and
      SS mRNA content, were similar in all experimental groups and in Controls and the
      same was true for plasma concentrations of free IGF-I. These results indicate
      that, similarly to obese female Zucker rats, also overfed female rats had a
      better preservation of the somatotrophic axis than their male counterparts. In
      diet-induced obese rats, also the etiology of the impairment of somatotrophic
      axis seems to be gender-related i.e. due to a reduction of gonadal function in
      males and to an elevation of FFA in females.

PMID- 9284082
TI  - Kinetics of adenovirus-mediated gene transfer to human lung fibroblasts.
AB  - Many features of Ad-mediated gene transfer to human lung fibroblasts are not well
      understood. We tested kinetics of transduction efficiency of LacZ gene to human
      lung fibroblasts by E1-deleted adenovriuses containing two different promoters,
      i.e. CMV and RSV LTR. A dose-dependent relationship between the vector
      multiplicity of infection (moi) and the efficiency of LacZ gene transfer to
      fibroblasts was observed with each vector, and higher moi of vectors achieved
      100% of transduction efficiency. Further, Ad-mediated gene transfer was enhanced
      by a long period of vector exposure to fibroblasts up to 6 hours. There were no
      differences in transduction efficiency between the two Ad vectors. LacZ gene
      expression by Ad vectors consistently decreased one day after infection. These
      results indicate that both Ad vectors are equally effective for gene transfer to
      human lung fibroblasts, and higher moi of vectors and/or a longer period exposure
      of fibroblasts to vectors can facilitate more efficient transduction of LacZ
      reporter gene into human lung fibroblasts.

PMID- 9284083
TI  - Metabolism of administered triethylene tetramine dihydrochloride in humans.
AB  - Triethylene tetramine dihydrochloride (trien 2HCl) has been used for the
      treatment of Wilson's disease, which is characterized by the accumulation of
      copper in various organs. We previously developed an HPLC system for analyzing
      trien, and found a trien metabolite in the urine when trien was orally given to
      humans. In this study, the metabolite was identified as 1-N-acetyltriethylene
      tetramine (acetyltrien) by FAB-MS and 1H-NMR spectroscopy. Trien and acetyltrien
      were capable of combining with copper, iron and zinc. However, the chelating
      activity of acetyltrien was significantly lower than that of trien. When trien
      was given to healthy adults, the amount of trien excreted in the urine was about
      1% of the administered trien, whereas that of acetyltrien was about 8%. Most of
      the trien was excreted within the first 6 hours after the administration, while
      acetyltrien was excreted for over 26 hours. The urinary copper, iron and zinc
      levels all increased in parallel with the trien excretion.

PMID- 9284084
TI  - Differential scanning calorimetry and small angle x-ray diffraction study of the
      interaction of (R)-PAF, (R)-ET-18-OME and (R)-Lyso-PAF with model membranes.
AB  - (R)-PAF, (R)-ET-18-OMe and (R)-Lyso-PAF are ether phospholipid analogs exhibiting
      different biological activities. All three molecules are highly lipophilic and
      interact with cell membranes. The manner in which their interactions occur is
      relevant to their biological activities and may provide information on their
      mechanism(s) of action at the molecular level. We have studied the interactions
      of (R)-PAF, (R)-ET-18-OMe and (R)-Lyso-PAF with model membranes using
      differential scanning calorimetry (DSC). A concentration-dependence study with
      DSC shows that all three analogs induce similar changes in the thermotropic
      behavior of model membranes. All produce a slight decrease in the main phase
      transition temperature of DPPC bilayers (deltaTc = 0.3 to 1.4 degrees C) but have
      a more substantial effect on the pretransition (deltaTc = 0.8 to 4.5 degrees C).
      All three disorder phosphatidylcholine (PC) membranes but impart order to
      PC/cholesterol membranes. We have used small angle x-ray diffraction experiments
      to supplement the DSC evidence on the topography of the ether lipid analogs in
      the bilayers. All three appear to insert themselves in the bilayer with their
      long chain parallel with the membrane bilayer chains.

PMID- 9284085
TI  - Insulin like growth factor 1 increases vascular smooth muscle nitric oxide
      production.
AB  - Insulin like growth factor 1 (IGF-1) vasodilates, increases blood flow and lowers
      blood pressure; nitric oxide (NO) has been suggested to mediate some of these
      effects. We studied the role of IGF-1 in the regulation of NO production in
      vascular smooth muscle cells (VSMC). IGF-1 induced a concentration and time
      dependent increase in NO release from endothelium-denuded aortic rings. Pre
      incubation with cycloheximide or aminoguanidine blocked IGF-1-stimulated NO
      release. In addition, a six-fold increase in NO production by VSMC was seen upon
      incubation with IGF-1. These results suggest that IGF-1 induces NO release in
      VSMC through a process that involves new protein synthesis and the inducible
      isoform of nitric oxide synthase.

PMID- 9284086
TI  - Interactions between different antidepressants and morphine alter
      gastrointestinal transit in mice.
AB  - To determine different serotoninergic antidepressants' effects on the
      gastrointestinal (GI) inhibiting effect induced by morphine, mice were pretreated
      with mianserin (a tetracyclic antidepressant with multiple 5-HT receptor subtypes
      interactions) and with fluoxetine (a selective 5-HT reuptake inhibitor).
      Mianserin alone, produced gastrointestinal inhibition in a dose-dependent manner.
      Naloxone did not reverse this inhibiting effect, indicating that different
      mechanism of action are involved in morphine- and mianserin-induced inhibition of
      the gastrointestinal transit. Fluoxetine injected alone produced an increased
      propulsive motility of the GI transit. This effect was not reversed by naloxone.
      Fluoxetine did not reduce significantly mianserin-induced inhibition of GI
      transit. Fluoxetine also mildly reversed morphine-induced gastrointestinal
      inhibition, suggesting some degree of involvement of the opiates through the
      serotoninergic system.

PMID- 9284087
TI  - AM630 is a competitive cannabinoid receptor antagonist in the guinea pig brain.
AB  - AM630 has been demonstrated to be a cannabinoid receptor antagonist in the mouse
      brain and vas deferens. Conversely, it was recently reported that AM630 acts as a
      cannabinoid agonist in the guinea pig ileum. This research was designed to
      determine whether the difference in the action of AM630 is species specific.
      Studies conducted in guinea pig brain reveal that AM630 antagonizes the
      stimulatory effect of the cannabinoid agonist WIN 55,212-2 on [35S]GTPgammaS
      binding suggesting that difference in AM630 activity in different tissues is not
      due to species variation.

PMID- 9284088
TI  - HIV-1 protein gp120 crosses the blood-brain barrier: role of adsorptive
      endocytosis.
AB  - HIV-1 infects the brain and leads to AIDS dementia complex. The viral coat
      glycoprotein, gp120, may facilitate the passage of HIV-1 and HIV-infected immune
      cells across the blood-brain barrier (BBB). Since the endothelial cells of the
      BBB do not possess the CD4 or galactosylceramide binding sites used by gp120 to
      induce HIV-1 uptake into other cell types, how gp120 mediates entry into brain is
      unknown. We postulate that gp120 crosses the BBB and does so by acting as a weak
      lectin to induce adsorptive endocytosis (AE) in a fashion similar to other
      glycoproteins like wheatgerm agglutinin (WGA). We found in vivo that gp120
      crosses the BBB and its passage is enhanced 18.7-fold by WGA. In vitro studies
      confirm that WGA enhances uptake of gp120 by brain endothelia; most of the uptake
      is membrane-associated, as expected in AE. Uptake is not dependent on clatharin,
      caveolae, calcium channels, or endosomal acidification. Our results suggest that
      gp120 crosses the BBB and does so by acting as a lectin to induce AE.

PMID- 9284089
TI  - Epidermal T cells: their functional role and disease relevance for
      dermatologists.
AB  - T cells found within the epidermis in inflammatory dermatoses are generally
      accepted as making a major contribution to epidermal damage. On the other hand,
      those T cells residing in the murine epidermis are supposed to play an important
      role in protecting the epidermis from potentially dangerous immune reactions.
      Overwhelming evidence has accumulated that dendritic epidermal T cells (DETC)
      expressing monomorphic TCR gammadelta are responsible for the protection of
      epidermal structures against skin tumor, bacterial infection, and autoimmune
      attack. In animals congenitally lacking these gammadelta+ DETC, the epidermis is
      populated with bone marrow-derived TCR alphabeta+, CD8+ DETC. Although it remains
      unclear whether this subset of DETC could home to the epidermis to substitute for
      the physiologic function of gammadelta+ DETC or whether they would be
      pathologically relevant to epidermal injury, it should be noted that this subset
      represents the major fraction of T cells present in normal human epidermis and
      the most abundant in the lesional epidermis of fixed drug eruption (FDE). Because
      they are shown to kill target cells including keratinocytes upon stimulation and
      utilize a very limited range of TCR V alpha and Vbeta gene families, localized
      epidermal injury in FDE lesions would be mediated by activation of these
      epidermal T cells with autoaggressive potential. Epidermal T cells are thus
      likely to form several T-cell populations with different immunologic functions
      that are triggered by different modes of stimulation. Immune homeostasis in the
      epidermis would rely on a delicate balance between at least two types of
      epidermal T cells: autoaggressive T cells and protective T cells.

PMID- 9284090
TI  - 1,25-dihydroxyvitamin D3, transforming growth factor beta1, calcium, and
      ultraviolet B radiation induce apoptosis in cultured human keratinocytes.
AB  - Apoptosis is a cellular process of self-directed suicide that plays a key role
      during morphogenesis and in the maintenance of homeostasis in continuously
      renewing tissues. Currently, apoptosis is detected mainly by gel electrophoresis
      of fragmented DNA and by typical ultrastructural features such as cell shrinkage
      and chromatin condensation. Recently, an in situ technique was developed that
      allows the detection of the apoptotic process in cells and the quantitation of
      apoptosis in cell populations. We applied this technique to evaluate the
      apoptotic process in cultured normal human keratinocytes under basic conditions
      and after stimulation with factors and agents that are presumed but have never
      been proved to induce apoptosis in these cells. Apoptosis was analyzed after
      stimulation with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], transforming growth
      factor beta1 (TGFbeta1), calcium, UVB, or tumor necrosis factor alpha (TNFalpha).
      All these factors except TNFalpha induced apoptosis in human keratinocytes.
      Whereas UVB and calcium were good apoptogenic stimuli at 6 and 24 h,
      respectively, the vitamin D derivative and TGFbeta1 induced apoptosis after 5 and
      6 d in culture. Apoptosis was also established by DNA fragmentation and electron
      microscopy. Finally, TUNEL technique showed that the number of apoptotic cells
      increases slightly (5-10%) from 24 to 144 h even in untreated keratinocytes. Our
      studies indicate that factors normally involved in the regulation of cell growth
      and differentiation can also control apoptosis.

PMID- 9284092
TI  - Regulation of pigmentation in cultured skin substitutes by cytometric sorting of
      melanocytes and keratinocytes.
AB  - Unpredictable pigmentation in cultured skin substitutes (CSS) is an anatomic
      deficiency after wound treatment and can require years to normalize. Variable
      numbers of human melanocytes (HM) survive in cultures of human keratinocytes (HK)
      as demonstrated by focal areas of pigmentation in CSS after healing. The purposes
      of this study were to deplete HM from HK cultures and to regulate the numbers of
      HM contained in CSS. A highly pigmented HM cell strain was chosen for these
      studies to emphasize the differences in light scattering between HK and HM by
      flow cytometry. Cytometric gates were set with selective cultures of HM and HK
      and were used to sort a mixed population of HK + 4% HM. After sorting, CSS were
      prepared from human fibroblasts attached to collagen-glycosaminoglycan sponges
      combined with cells from the HK + 4% HM (pre-treatment control), the sorted HK
      (experimental), or sorted HK + 3% HM (post-treatment positive control)
      subpopulations and grafted to athymic mice. Grafted wounds were assessed for 6 wk
      by planimetry for area of pigment and by a Minolta Chromameter for color density
      and hue in situ. Histology and staining of HLA-ABC were performed at 6 wk. Data
      from percent pigmented area and chromameter measurements identified quantitative
      and statistically significant decreases in color of healed skin after flow
      cytometric separation of HK and HM. Therefore, a purified HK subpopulation
      depleted of HM was isolated by flow cytometry that generated healed skin with
      reduced pigmentation. These results suggest that HM can be selectively depleted
      from HK cultures and then added to cultured skin substitutes at specific
      densities to generate predictable pigmentation for improved function and cosmesis
      in healed wounds.

PMID- 9284091
TI  - T-lymphocyte dependence of psoriatic pathology in human psoriatic skin grafted to
      SCID mice.
AB  - Considerable indirect evidence suggests that T lymphocytes have a role in the
      pathogenesis of psoriasis. The goal of this study was to directly test the
      ability of T cells to maintain psoriasis pathology. Psoriatic skin was
      transplanted onto SCID mice, which were then injected with autologous T cells. T
      cells were cultured from either psoriatic skin lesions or peripheral blood and
      injected intradermally or intravenously. Control SCID mice transplanted with
      psoriasis grafts were not injected with T cells. After 10 wk, control psoriatic
      skin grafts not injected with T cells lost many of the features of psoriasis.
      Injection of peripheral blood T cells was not able to maintain these psoriatic
      features. In contrast, the injection of T cells derived from psoriatic skin was
      able to maintain the psoriatic phenotype. Psoriatic features that were maintained
      included epidermal thickness and labeling index and expression of HLA-DR,
      involucrin, and ICAM-1, as well as loss of expression of filaggrin. Injection of
      skin infiltrating T cells into skin of normal donors on SCID mice did not induce
      changes of psoriasis. The ability of T cells from lesional skin, but not
      peripheral blood, to maintain psoriasis suggests that psoriasis is mediated by an
      autoantigen reactive T cell, which is present at a higher frequency in the
      psoriatic lesion.

PMID- 9284093
TI  - Different levels of 5alpha-reductase type I and II, aromatase, and androgen
      receptor in hair follicles of women and men with androgenetic alopecia.
AB  - In this study, 12 women and 12 men, ages 18-33 y, with androgenetic alopecia were
      selected for biopsies from frontal and occipital scalp sites. The androgen
      receptor, type I and II 5alpha-reductase, cytochrome P-450-aromatase enzyme were
      measured and analyzed in hair follicles from these scalp biopsies. Findings
      revealed that both women and men have higher levels of receptors and 5alpha
      reductase type I and II in frontal hair follices than in occipital follicles,
      whereas higher levels of aromatase were found in their occipital follicles. There
      are marked quantitative differences in levels of androgen receptors and the three
      enzymes, which we find to be primarily in the outer root sheath of the hair
      follicles in the two genders. Androgen receptor content in female frontal hair
      follicles was approximately 40% lower than in male frontal hair follicle.
      Cytochrome P-450-aromatase content in women's frontal hair follicles was six
      times greater than in frontal hair follicles in men. Frontal hair follicles in
      women had 3 and 3.5 times less 5alpha-reductase type I and II, respectively, than
      frontal hair follicles in men. These differences in levels of androgen receptor
      and steroid-converting enzymes may account for the different clinical
      presentations of androgenetic alopecia in women and men.

PMID- 9284094
TI  - Unoccluded retinol penetrates human skin in vivo more effectively than unoccluded
      retinyl palmitate or retinoic acid.
AB  - The formation of all-trans retinoic acid is an oxidative process whereby retinol
      is converted to retinaldehyde and then to retinoic acid. Because retinol causes
      qualitative molecular changes similar to those produced by retinoic acid, we
      compared potency of retinol, retinaldehyde, and retinyl palmitate to retinoic
      acid and assessed the effects of occlusion. Retinoids were prepared in an
      experimental vehicle of 95% ethanol:propylene glycol (7:3) with anti-oxidant.
      Induction of retinoic acid 4-hydroxylase activity was the end point for
      comparison. Retinoic acid concentrations from 0.001% to 0.05% under occlusion
      produced a linear dose-response induction of 4-hydroxylase activity. The
      concentrations of the other retinoids under occlusion required to achieve
      significant induction of enzyme activity were 0.6% retinyl palmitate, 0.025%
      retinol, and 0.01% retinaldehyde. The linear dose-response was lost with retinoid
      concentrations in excess of 0.25% retinol or 0.5% retinaldehyde. Statistical
      analyses showed no difference in 4-hydroxylase activity between unoccluded and
      occluded retinol treated sites. By contrast, however, unoccluded sites treated
      with retinoic acid or retinyl palmitate had less induction of 4-hydroxylase
      activity than occluded sites. Retinol, retinaldehyde, and retinyl palmitate did
      not produce erythema but did increase epidermal thickness. Although retinol is a
      weaker retinoid than retinoic acid, the increased penetration of unoccluded
      retinol in comparison to unoccluded retinoic acid with this prototypic vehicle
      confers on retinol a more effective delivery of a retinoidal effect than
      unoccluded retinoic acid. Retinol at 0.25% may be a useful retinoid for
      application without occlusion because it does not irritate but does induce
      cellular and molecular changes similar to those observed with application of
      0.025% retinoic acid.

PMID- 9284095
TI  - PCR-RFLP analysis as an aid to genetic counseling of families of Japanese
      patients with group A xeroderma pigmentosum.
AB  - Because Japanese patients with complementation group A xeroderma pigmentosum (XP
      A) show early skin cancer and severe neurologic dysfunction, their family members
      are greatly concerned about the risk of inherited disease. In contrast to western
      XP-A patients, almost all Japanese XP-A patients have two of the three mutations
      (nonsense mutation in exon 3, splicing mutation in intron 3, and non-sense
      mutation in exon 6), which are easily detected by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) analysis. This work was aimed
      to see whether PCR-RFLP analysis is useful for genetic counseling of XP patients'
      siblings who are potential carriers of an XP-A gene mutation. In two of the three
      case studies presented, the probands were homozygous for the splicing mutation in
      intron 3 of the gene. In their siblings receiving genetic counseling, no mutation
      was found in the mutation site in one case, and one splicing mutation was found
      in the second case. In the third case, the proband was a compound heterozygote
      for the splicing mutation and for an unidentified mutation; in her sibling, no
      mutation was found in either of these mutation sites. No mutation was found in
      the siblings' spouses. On the basis of these findings, we reassured the
      prospective parents that there was little probability of having XP children, but
      in the second and third cases, we told them that their apparently unaffected
      children might be carriers. Each couple subsequently had one unaffected child.
      Thus, PCR-RFLP analysis is useful for genetic counseling of family members of XP
      A patients.

PMID- 9284096
TI  - Increased sensitivity to peroxidative agents as a possible pathogenic factor of
      melanocyte damage in vitiligo.
AB  - To examine the sensitivity of vitiligo melanocytes to external oxidative stress,
      we studied enzymatic and non-enzymatic anti-oxidants in cultured melanocytes of
      normal subjects (n = 20) and melanocytes from apparently normal skin of vitiligo
      patients (n = 10). The activity of superoxide dismutase and catalase and the
      intracellular concentrations of vitamin E and ubiquinone were evaluated in
      cultures at the fourth or fifth passage. In addition, cells were exposed to
      various concentrations of a peroxidizing agent, cumene hydroperoxide (CUH, 0.66
      20 microM), for 1 and 24 h. Compared to normal melanocytes, vitiligo melanocytes
      showed normal superoxide dismutase and significantly lower catalase activities
      and higher vitamin E and lower ubiquinone levels. At the concentration used, CUH
      did not significantly affect cell number or viability of melanocytes after either
      period of culture. On the contrary, vitiligo melanocytes were susceptible to the
      toxic effect of CUH after 24 h of continuous treatment at concentrations greater
      than 6.6 microM. The degree of CUH toxicity correlated strictly with the anti
      oxidant pattern, defined as the ratio between vitamin E concentration and
      catalase activity, suggesting that the alteration in the antioxidants was the
      basis for sensitivity to the external oxidative stress. Our results demonstrate
      the presence of an imbalance in the anti-oxidant system in vitiligo melanocytes
      and provide further support for a free radical-mediated damage as an initial
      pathogenic event in melanocyte degeneration in vitiligo.

PMID- 9284097
TI  - Glutathione metabolism in mice is enhanced more with hapten-induced allergic
      contact dermatitis than with irritant contact dermatitis.
AB  - Cutaneous inflammation induced by electrophilic compounds involves irritant
      contact dermatitis (ICD) and allergic contact dermatitis (ACD). Reduced
      glutathione (GSH) and related thiols have been postulated to play important roles
      in detoxification of electrophilic xenobiotics, protection of tissues against
      reactive oxygen species, and modulation of immunologic functions in normal and
      diseased subjects. The dynamic aspects of GSH metabolism, however, and its
      significance in patients with ICD and ACD remain to be clarified. The current
      study was carried out to elucidate the pathogenesis and possible involvement of
      GSH in both types of inflammation. Normal mice and mice sensitized with
      dinitrochlorobenzene (DNCB) were challenged by cutaneous administration of DNCB,
      and changes in GSH metabolism in skin and liver were determined. Kinetic analysis
      revealed that 24 h after challenge with DNCB, levels of hepatic glutathione and
      its secretion increased more markedly in the sensitized mice than in the
      unsensitized animals. Administration of buthionine-L-sulfoximine (BSO), a
      specific inhibitor of GSH synthesis, inhibited the increase in glutathione levels
      in the liver and the skin of both groups. Histologic examination revealed that
      cutaneous inflammation was enhanced by BSO more significantly in mice with ACD
      than with ICD. These results suggest that GSH might play an important role in the
      suppression of the immune reaction in mice with ACD.

PMID- 9284098
TI  - Decreased level of prosaposin in atopic skin.
AB  - In the skin of atopic dermatitis patients, the amount of ceramides in the stratum
      corneum is decreased. Although the cause of this decrease may be due to the
      higher activity of acylase, a decrease in the activity of sphingolipid activator
      proteins may also be the cause. A polyclonal antibody to saposin D, elicited by
      immunizing rabbits with the synthetic polypeptide from cDNA of saposin D, cross
      reacted with a single 65-kDa epidermal protein of pI 5.6 in a 2-dimensional
      immunoblot study, suggesting that it was prosaposin, the precursor protein of
      saposin D, from its molecular weight and demonstrating its immunohistochemical
      localization in the innermost cell layers of the stratum corneum of the skin. The
      antigenic material was also observed in the epithelium of the esophagus,
      pneumocytes of the lungs, hepatocytes, and glandular cells of the stomach.
      Immunoelectron microscopy showed the antigenic material in the cytoplasm of the
      granular cells and the intercellular spaces, either between the stratum
      granulosum and the stratum corneum or on the stratum corneum cell envelope. By
      ELISA, the amount of the 65-kDa protein in the inner surface skin of the upper
      arm of atopic dermatitis patients (nonlesional skin) [4.1 +/- 2.0 microg per 7
      mm2 (mean +/- SD), n = 10] was found to be significantly decreased (p < 0.05) to
      66% of that in the normal control (6.2 +/- 1.5 microg per 7 mm2, n = 10).
      Therefore, the suppression of prosaposin synthesis may be related to the abnormal
      stratum corneum formation in atopic skin through lower activation of
      glucosylcerebrosidase or sphingomyelinase.

PMID- 9284099
TI  - Vesicle formation and follicular root sheath separation in mice homozygous for
      deleterious alleles at the balding (bal) locus.
AB  - The balding (bal) mutation of the mouse is an autosomal recessive mutation that
      causes alopecia and immunologic anomalies. A new allele was identified by
      allelism testing after using an interspecific backcross to localize the mutation
      to the centromeric end of mouse chromosome 18. We investigated the skin and hair
      histologic lesions of two alleles (bal(J) and bal(Pas)) at this locus and
      analyzed the expression of several keratinocyte markers and the production of
      autoantibodies by immunofluorescence on frozen skin sections. The lesions
      observed included separation of the inner and outer root sheath in anagen
      follicles resulting in the hair fiber being very easily plucked from the
      follicle. Vesicles on the ventral tongue, mucocutaneous junction of the eyelid,
      foot pads, and rarely in skin were also evident. Separation occurred between the
      basal and suprabasilar cells forming an empty cleft, resembling that observed in
      human pemphigus vulgaris. Immunofluorescence studies did not reveal the presence
      of tissue-bound or circulating autoantibodies. Expression of keratinocyte markers
      in hair follicles was normal. Keratin 6-positive cells were found on either side
      of the follicular separation suggesting a molecular defect in adhesion molecules
      between the inner layer of the outer root sheath cells to layers on either sides.
      This hypothesis has been confirmed by another group who demonstrated that the
      bal(J) mutation is due to the insertion of a thymidine in the desmoglein 3 gene,
      resulting in a premature stop codon.

PMID- 9284100
TI  - Autoantibodies to hair follicles in C3H/HeJ mice with alopecia areata-like hair
      loss.
AB  - We have previously described spontaneous but reversible hair loss that clinically
      and histologically resembles human alopecia areata in a colony of C3H/HeJ mice.
      Alopecia areata in humans is associated with antibodies to hair follicles. This
      study was conducted to determine whether C3H/HeJ mice with hair loss have a
      similar abnormal antibody response to hair follicles. Eighteen C3H/HeJ mice with
      alopecia, 12 unaffected littermates, and 15 control mice were examined for
      circulating antibodies to C3H/HeJ anagen hair follicles by indirect
      immunofluorescence and against extracts of isolated C3H/HeJ and human anagen hair
      follicles by immunoblotting. Using both procedures, antibodies to anagen hair
      follicles were present in all C3H/HeJ mice with alopecia but in none of the
      control mice. The antibodies were also present in some unaffected C3H/HeJ
      littermates but were absent in mice of an unrelated strain with inflammatory skin
      disease and alopecia, indicating that their appearance did not result from the
      hair loss. These antibodies reacted to hair follicle-specific antigens of 40-60
      kDa present in murine and human anagen hair follicles. These antigens were also
      reactive with human alopecia areata antibodies. Some of the antibodies in both
      C3H/HeJ mice and humans with alopecia areata reacted to antigens of 44 and 46
      kDa, which were identified as hair follicle-specific keratins. This study
      indicates that C3H/HeJ mice with hair loss have circulating antibodies to hair
      follicles similar to those present in humans with alopecia areata. These findings
      confirm that these mice are an appropriate model for human alopecia areata and
      support the hypothesis that alopecia areata results from an abnormal autoimmune
      response to hair follicles.

PMID- 9284101
TI  - The co-culture of dermal fibroblasts with human epidermal keratinocytes induces
      increased prostaglandin E2 production and cyclooxygenase 2 activity in
      fibroblasts.
AB  - During wound healing, cell-cell interactions between epidermal keratinocytes and
      dermal fibroblasts contribute to the organization of epidermis, in which
      prostaglandin E2 (PGE2) is considered to be involved in proliferation and
      differentiation of keratinocytes. In the current study, we investigated the
      regulation of PGE2 biosynthesis in co-culture of human epidermal keratinocytes
      and human dermal fibroblasts. The production of PGE2 was synergistically enhanced
      in the co-culture at cell ratios of keratinocytes to fibroblasts between 1/8 and
      4, whereas the production of PGE2 was negligible in individual monolayer cultures
      of keratinocytes or fibroblasts. To address the mechanism of PGE2 production
      induced by the co-culture of keratinocytes and fibroblasts, we asked whether
      either cell-derived soluble factor(s) or direct cell-cell contact was required to
      augment the production of PGE2. Neither the fibroblast-conditioned medium nor
      membrane fractions influenced the production of PGE2 in keratinocytes.
      Keratinocyte-conditioned medium greatly enhanced the production of PGE2 in
      fibroblasts, however, whereas the effect of keratinocyte-membrane fractions was
      weaker. The main soluble fraction in the keratinocyte-conditioned medium
      contained a precursor of interleukin-1 alpha (proIL-1alpha) by western blot
      analysis, and PGE2 production was inhibited by anti-IL-1alpha antibody, but not
      by anti-IL-1beta or by anti-tumor necrosis factor-alpha antibody. The enhanced
      production of PGE2 in fibroblasts upon culturing with keratinocytes was due to
      the induction of COX-2 mRNA mediated by proIL-1alpha released from keratinocytes.
      These results suggest that cell-cell interactions of keratinocytes and
      fibroblasts augment the production of PGE2 by a mechanism in which the activity
      of COX-2 in fibroblasts is increased by the keratinocyte-derived proIL-1alpha in
      a paracrine manner.

PMID- 9284103
TI  - The formation of competent barrier lipids in reconstructed human epidermis
      requires the presence of vitamin C.
AB  - Our analysis of epidermal lipids revealed that (glucosyl)ceramide profiles in
      various human skin equivalents are different from those of native tissue. The
      main difference is the reduced content in skin equivalents of ceramides 4-7 and
      especially the very low content of the most polar ceramides 6 and 7, which
      contain hydroxylated sphingoid base and/or fatty acid. To facilitate
      hydroxylation, the culture medium was supplemented with vitamins C and E.
      Although in vitamin E-supplemented medium lipogenesis was not affected, in
      vitamin C-supplemented medium the content of glucosylceramides and of ceramides 6
      and 7 was markedly increased, both in the presence and absence of serum and
      irrespective the substrate used (inert or natural, populated or not with
      fibroblasts). The improvement of the lipid profile was accompanied by a marked
      improvement of the barrier formation as judged from extensive production of
      lamellar bodies, their complete extrusion at the stratum granulosum/stratum
      corneum interface, and the formation of multiple broad lipid lamellar structures
      in the intercorneocyte space. The presence of well-ordered lipid lamellar phases
      was confirmed by small-angle x-ray diffraction. Some differences between native
      and reconstructed epidermis, however, were noticed. Although the long-range lipid
      lamellar phase was present in both the native and the reconstructed epidermis,
      the short lamellar phase was present only in native tissue. It remains to be
      established whether these differences can be ascribed to small differences in
      relative amounts of individual ceramides, to differences in fatty acid profiles,
      or to differences in cholesterol sulfate, pH, or calcium gradients. The results
      indicate the key role vitamin C plays in the formation of stratum corneum barrier
      lipids.

PMID- 9284102
TI  - Epidermal proliferation but not quantity of DNA photodamage is correlated with UV
      induced mouse skin carcinogenesis.
AB  - The hairless SKH-1 mouse strain has a higher skin tumor incidence, shorter tumor
      latency, and higher tumor yield in response to ultraviolet (UV) irradiation than
      the SENCAR strain. In this study we assessed the differences in UV susceptibility
      of both strains by measuring DNA photodamage and epidermal proliferation after
      one UV treatment and after 1, 3, 6, and 9 wk of chronic UV irradiation. Induction
      rates for cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone
      photoproducts [(6-4) PDs] were significantly greater in the SKH-1 strain than the
      SENCAR strain, but no strain differences in repair kinetics were detected for
      CPDs or (6-4) PDs. With chronic UV exposure we observed the following: (i) there
      was an equal amount of DNA photodamage in both strains; (ii) the number of (6-4)
      PDs was significantly greater than the CPDs after 6 wk; (iii) there were a
      significantly greater number of epidermal cells (1.5-fold increase) in the SKH-1
      strain; (iv) the number of cycling cells, as measured by 5-bromo-2'-deoxyuridine
      (BrdU), were located both basally and suprabasally and were significantly greater
      in the SKH-1 strain; and (v) the number of cells immunoreactive to p53 was
      equivalent in both strains, but immunoreactive cells were located suprabasally in
      the SKH-1 strain after 9 wk of UV. These results show that the etiologic role of
      UV in tumorigenesis is dependent on events other than the amount of DNA
      photodamage in mouse epidermis.

PMID- 9284104
TI  - LAD-1 is absent in a subset of junctional epidermolysis bullosa patients.
AB  - The anchoring filament protein LAD-1 has been recently identified as the target
      of autoantibodies in the acquired blistering disorder linear IgA bullous
      dermatosis. Because this protein appears to be involved in the process of dermal
      epidermal cohesion, this study sought to determine the involvement of LAD-1 in
      the pathology of junctional epidermolysis bullosa (JEB). To this end, 44 patients
      with a variety of subtypes of JEB were analyzed by indirect immunofluorescence
      microscopy with antibodies to LAD-1, BP180, and laminin-5. We found that only
      patients with generalized atrophic benign epidermolysis bullosa (GABEB) contained
      LAD-1 defects. Of the 16 GABEB patients studied, 13 showed absent or greatly
      reduced expression of LAD-1 (including 2 patients with a peculiar interrupted
      staining pattern) and 3 patients showed defects of laminin-5 expression with
      normal LAD-1 expression. Patients who showed LAD-1 defects also showed abnormal
      expression of BP180. Keratinocytes were cultured from the skin of two GABEB
      patients and analyzed by indirect immunofluorescent microscopy. One culture
      demonstrated defects of BP180 and LAD-1 expression (which was also verified by
      radioimmunoprecipitation assay), and one culture showed decreased laminin-5
      expression but normal BP180 and LAD-1 expression. Thus, these studies demonstrate
      that: (i) LAD-1 and BP180 are normally expressed in all subtypes of JEB except
      GABEB, (ii) the majority of GABEB patients show absent or near absent expression
      of both LAD-1 and BP180 but normal expression of laminin-5, and (iii) a smaller
      subset of GABEB patients show normal LAD-1 and BP180 expression but express
      persistent but reduced levels of laminin-5.

PMID- 9284105
TI  - Partial dominance of a keratin 14 mutation in epidermolysis bullosa simplex-
      increased severity of disease in a homozygote.
AB  - Epidermolysis bullosa simplex is a disease in which keratin gene mutations cause
      the production of defective intermediate filaments, which leads in turn to
      epidermal basal cell fragility and blistering. The inheritance in nearly all
      kindreds is autosomal dominant, most kindreds have missense mutations, and the
      encoded proteins appear to exert a dominant negative function. One previously
      reported patient with generalized blistering had a fully dominant mutation of
      keratin 5; in that kindred a homozygote was affected no more severely than the
      heterozygotes. By contrast we report here a keratin 14 mutation that causes
      blistering limited to the hands and feet in heterozygotes, but homozygotes have
      more severe, widespread blistering of the skin and mucous membranes. Thus keratin
      gene mutations may be not only fully recessive or fully dominant but also
      partially dominant as well.

PMID- 9284106
TI  - cDNA cloning of the 210-kDa paraneoplastic pemphigus antigen reveals that
      envoplakin is a component of the antigen complex.
AB  - Although the 210 and 190-kDa proteins are the most frequently detected antigens
      reacting with sera of patients with paraneoplastic pemphigus (PNP) in immunoblot
      analysis, there is still uncertainty as to the nature of these PNP antigens. To
      isolate and characterize a cDNA clone encoding the 210-kDa PNP antigen, we
      screened a human keratinocyte lambda gt 11 cDNA expression library by the
      immunoperoxidase method with serum IgG from a PNP patient. The IgG used for the
      immunoscreening of a keratinocyte cDNA expression library recognized 210- and 190
      kDa antigens by immunoblotting. A single clone, called here the PNP clone,
      producing a fusion protein that reacted strongly with the patient's IgG, was
      further characterized. Only the PNP patient's IgG, but not IgG from a normal
      control, pemphigus foliaceus, or pemphigus vulgaris patients, bound the plaques
      of this positive clone. Furthermore, PNP IgG affinity purified on plaques of this
      clone, but not unrelated clones, bound to keratinocyte cell surfaces by
      immunofluorescence and reacted with the 210-kDa PNP antigen by immunoblotting.
      EcoRI digestion of the clone's cDNA insert demonstrated a 1.4-kbp fragment. This
      cDNA insert was placed into a M13 mp 18 vector and sequenced. Sequence analysis
      revealed that the cDNA insert of the PNP clone encodes a part of the central rod
      domain and the COOH-terminal C domain of envoplakin, a newly defined precursor of
      the cornified envelope that is homologous to desmoplakin. This result
      demonstrates that the 210-kDa PNP antigen is envoplakin and PNP is an autoimmune
      disease that produces autoantibodies against intermediate filament-associated
      proteins in desmosomes and hemidesmosomes, desmoplakin, bullous pemphigoid
      antigen 1 (BPAG 1), and envoplakin.

PMID- 9284107
TI  - The effects of trypsin on apoptosis, utriculi size, and skin elasticity in the
      Rhino mouse.
AB  - Acne vulgaris is the result of multifactorial disorders of the pilosebaceous
      duct. The initial lesion is believed to be hyper-keratinization of the
      infundibulum. The Rhino mouse has been used as an experimental acne model system
      for screening anti-keratinizing and comedolytic agents. Using this system we show
      that trypsin could induce desquamation and utriculi-epidermal differentiation in
      the absence of irritation. Following five daily trypsin treatments, the
      biomechanical properties of the mouse skin improved, as demonstrated by cutometer
      measurements and increased elastin expression. Extensive programmed cell death
      and apoptosis are demonstrated in the utriculi epithelium of the untreated
      animals. This cell death is eliminated by the trypsin treatment. We speculate
      that co-administration of trypsin might increase the therapeutic value of topical
      acne treatments and improve skin elasticity while reducing irritating effects.

PMID- 9284108
TI  - Retroviral transduction of murine epidermal stem cells demonstrates clonal units
      of epidermal structure.
AB  - It has been suggested that the number and position of epidermal stem cells are
      related to the units of columnar structure in the upper epidermal strata and that
      the cells of each unit are derived from a single stem cell. Studies of cell
      lineage in developing tissues have been facilitated by the use of retroviral
      transduction to provide inherited expression of a histochemically demonstrable
      foreign gene product. To provide direct evidence about the clonal nature of
      epidermal units, murine epidermal keratinocytes were transduced with a
      replication-deficient retroviral vector carrying the beta-galactosidase gene.
      Subepidermal injection of virus in vivo led to infrequent transduction with only
      transient presence of beta-gal-staining keratinocytes within the epidermis.
      Transduction of keratinocytes in vitro and transplantation back to in vivo sites
      permitted demonstration of the transduced gene in clusters of cells within the
      reformed epidermis throughout a 12-wk period. The epidermis redeveloped an
      ordered columnar structure with restriction of transduced cells to individual
      columnar units. This clonal appearance is compatible with derivation of each
      epidermal unit from a single stem cell but is not compatible with a random
      pattern of cell proliferation. Transduced epidermal sheets that were recombined
      with oral mucosal connective tissue also redeveloped normal columnar structure
      with restriction of beta-gal staining to individual columnar units. These data
      suggest that the establishment of an epidermal stem cell pattern related to units
      of structure is an intrinsic property of the epithelium and is not dependent on
      regionally-specific connective tissue influences.

PMID- 9284109
TI  - A combination of a common splice site mutation and a frameshift mutation in the
      COL7A1 gene: absence of functional collagen VII in keratinocytes and skin.
AB  - We describe a patient with severe generalized dystrophic epidermolysis bullosa
      (EBD) and a novel combination of compound heterozygous mutations in the COL7A1
      gene. The maternal mutation was an A-to-G transition (425-A --> G) at position -2
      of the donor splice site within exon 3 that causes aberrant splicing of two
      abnormal transcripts. One includes intron 3, and one excludes both exon 3 and
      intron 3. Both splice variants contained a premature termination of the
      translation. The paternal mutation is a 25-bp deletion in exon 20 (2638de125)
      that leads to a frameshift and a premature termination codon 133 bp downstream
      from the site of deletion. This combination of mutations allowed expression of
      collagen VII mRNA. Immunofluorescence staining of the patient's skin and cultured
      keratinocytes with domain-specific collagen VII antibodies, however, demonstrated
      markedly reduced levels of alpha1(VII) polypeptides, and no stable collagen VII
      protein could be extracted from the patient's cells. Electron microscopy showed
      severely hypoplastic fibrils below the lamina densa, without evidence of normal
      anchoring fibrils. The clinically unaffected parents were heterozygous for the
      mutations, suggesting that both COL7A1 gene defects were recessively inherited
      disease-causing mutations that are "silent" in heterozygous carriers but in
      combination can severely interfere with the dermal-epidermal adhesion and lead to
      severe EBD.

PMID- 9284110
TI  - Premature termination codon mutations in the type VII collagen gene in recessive
      dystrophic epidermolysis bullosa result in nonsense-mediated mRNA decay and
      absence of functional protein.
AB  - The severe mutilating Hallopeau-Siemens type of recessive dystrophic
      epidermolysis bullosa (HS-RDEB) is characterized by the absence of anchoring
      fibrils that consist of type VII collagen. We have previously identified
      premature termination codon (PTC) mutations in both alleles of the type VII
      collagen gene (COL7A1) in HS-RDEB patients. In this study we have defined the
      mechanism by which these mutations elicit their phenotypic consequences in a
      family. The extent of nonsense-mediated mRNA decay induced by these mutations was
      assessed by quantitation of the level of expression of the corresponding mRNA
      from each of the mutant alleles by RT-PCR of parental RNA. The level of
      expression of the paternal mutant allele with a PTC in exon 2 was approximately
      30% of that of the wild-type allele whereas that of the maternal mutant allele
      with a PTC in exon 104 was reduced to about 80% of the normal allele.
      Immunoprecipitation of newly synthesized type VII collagen with a monoclonal
      antibody revealed reduced quantities of alpha1(VII) polypeptides in both parents'
      cells, whereas their synthesis was entirely absent in the proband's
      keratinocytes. Thus, a consequence of these premature termination codon mutations
      in COL7A1 is nonsense-mediated mRNA decay, with a dramatic reduction in type VII
      collagen synthesis, and the absence of anchoring fibrils in the proband. These
      results establish a mechanistic link between the presence of premature
      termination codon mutations in both alleles of COL7A1 and the clinical phenotype
      of HS-RDEB.

PMID- 9284111
TI  - Sunscreen and immunosuppression.

PMID- 9284112
TI  - Mast cells in infection and immunity.

PMID- 9284113
TI  - Low antigenicity of the polysaccharide region of Helicobacter pylori
      lipopolysaccharides derived from tumors of patients with gastric cancer.
AB  - We have examined the antibody response to Helicobacter pylori lipopolysaccharide
      (LPS) during natural infection in humans. The sera of over 70% of H. pylori
      infected individuals were found to contain immunoglobulin G antibodies against
      the LPS fractions isolated from smooth strains of H. pylori but not against those
      derived from rough strains, as determined by enzyme-linked immunosorbent assay.
      These results taken together with the immunoblot data indicated that the
      polysaccharide region of H. pylori LPS is antigenic in humans. However, the
      antigenicity of the polysaccharide varied, depending on the strain. We found that
      smooth H. pylori strains isolated from the tumors of patients with gastric cancer
      showed significantly lower antigenicity than smooth strains derived from patients
      with chronic gastritis and gastric and duodenal ulcers. The results suggest that
      the levels of antigenicity of the polysaccharide region of H. pylori LPS in
      humans correlate with the nature of the gastroduodenal diseases and that they
      allow a particular distinction to be made between gastric cancer and other
      gastroduodenal diseases, especially chronic gastritis.

PMID- 9284114
TI  - Porphyromonas gingivalis lipopolysaccharide-stimulated bone resorption via CD14
      is inhibited by broad-spectrum antibiotics.
AB  - In the present study, we examined mechanisms of Porphyromonas gingivalis
      lipopolysaccharide (P-LPS)-stimulated bone resorption via CD14, one of the
      lipopolysaccharide (LPS) receptors, and also assessed the inhibitory action of
      several kinds of antibiotics on the LPS-induced stimulation. First, we observed
      by using mouse embryonic calvarial cells that P-LPS stimulated bone resorption
      through the action of endogenous interleukin-1beta (IL-1beta) and interleukin-6
      (IL-6) via CD14 because (i) P-LPS-stimulated expression of IL-1beta and IL-6
      genes in calvarial cells was inhibited by an anti-mouse CD14 antibody, (ii)
      stimulated bone resorption was markedly inhibited by both IL-1beta and IL-6
      antibodies, and (iii) P-LPS-stimulated bone resorption was clearly neutralized by
      an anti-mouse CD14 antibody. Next, we examined the effects of several kinds of
      antibiotics on P-LPS-stimulated bone resorption via CD14. Two of them,
      chloramphenicol and erythromycin, inhibited P-LPS-stimulated bone resorption in a
      dose-dependent manner. In an additional experiment, we observed that
      chloramphenicol clearly inhibited P-LPS-stimulated expression of the CD14, IL
      1beta, and IL-6 genes in calvarial cells. These results suggest that
      chloramphenicol might be a useful antibiotic as an anti-inflammatory agent
      against P-LPS-stimulated periodontal destruction occurring via CD14 in
      periodontal disease.

PMID- 9284115
TI  - Monophosphoryl lipid A enhances both humoral and cell-mediated immune responses
      to DNA vaccination against human immunodeficiency virus type 1.
AB  - To enhance immunity induced by DNA vaccination against human immunodeficiency
      virus type 1 (HIV-1), we evaluated the efficacy of monophosphoryl lipid A (MPL),
      an adjuvant of bacterial origin. BALB/c mice were intramuscularly injected with
      immunogenic DNA, encoding the env and rev genes of the HIV-1(IIIB) strain,
      formulated with MPL dissolved in different vehicles (MPL in stable emulsion and
      MPL in aqueous formulation). The sera from mice immunized with the two
      preparations of MPL revealed 2(6) to 2(9) times higher HIV-1-specific
      immunoglobulin G (IgG) titers than the sera from mice immunized without MPL. In
      virus neutralization tests for HIV-1(IIIB), by p24 assay and antifusion assay of
      infected MOLT-4 cells, MPL tends to elicit antibody more protective than antibody
      elicited without adjuvant. MPL also elicited stronger delayed-type
      hypersensitivity and cytotoxic-T-lymphocyte activity against HIV-1(IIIB) compared
      to DNA alone. HIV-1-specific IgG subclass analysis showed that MPL tends to
      facilitate IgG2a production, suggesting enhancement of a predominant T-helper
      type-1 response, and this enhancement may help to facilitate protective-antibody
      induction. Furthermore, a chloramphenicol acetyltransferase (CAT) assay was
      employed to determine whether MPL affected the gene expression process.
      Interestingly, both MPL preparations reduced CAT activity in the muscle injected
      with CAT expression vector but increased anti-CAT antibody production. These
      results indicate that MPL acts as an effective adjuvant for immunogenic DNA
      injection despite reduced expression of encoding protein in muscle. We conclude
      that MPL has a strong adjuvant effect on DNA vaccination against HIV-1.

PMID- 9284116
TI  - Disruption of each of the secreted aspartyl proteinase genes SAP1, SAP2, and SAP3
      of Candida albicans attenuates virulence.
AB  - Secreted aspartyl proteinases (Saps), encoded by a gene family with at least nine
      members (SAP1 to SAP9), are one of the most discussed virulence factors produced
      by the human pathogen Candida albicans. In order to study the role of each Sap
      isoenzyme in pathogenicity, we have constructed strains which harbor mutations at
      selected SAP genes. SAP1, SAP2, and SAP3, which are regulated differentially in
      vitro, were mutated by targeted gene disruption. The growth rates of all
      homozygous null mutants were similar to those of the isogenic wild-type parental
      strain (SC5314) in complex and defined media. In medium with protein as the sole
      source of nitrogen, sap1 and sap3 mutants grew with reduced growth rates but
      reached optical densities similar to those measured for SC5314. In contrast, sap2
      null mutants tended to clump, grew poorly in this medium, and produced the lowest
      proteolytic activity. Addition of ammonium ions reversed such growth defects.
      These results support the view that Sap2 is the dominant isoenzyme. When sap1,
      sap2, and sap3 mutants were injected intravenously in guinea pigs and mice, the
      animals had increased survival rates compared to those of control animals
      infected with SC5314. However, reduction of proteolytic activity in vitro did not
      correlate directly with the extent of attenuation of virulence observed for all
      Sap-deficient mutants. These data suggest that SAP1, SAP2, and SAP3 all
      contribute to the overall virulence of C. albicans and presumably all play
      important roles during disseminated infections.

PMID- 9284117
TI  - A triple deletion of the secreted aspartyl proteinase genes SAP4, SAP5, and SAP6
      of Candida albicans causes attenuated virulence.
AB  - Secreted aspartyl proteinases (Saps) from Candida albicans are encoded by a
      multigene family with at least nine members (SAP1 to SAP9) and are considered
      putative virulence factors important for the pathogenicity of this human
      pathogen. The role of Sap isoenzymes in the virulence of C. albicans has not yet
      been clearly established, and therefore, using recent progress in the genetics of
      this yeast, we have constructed a panel of isogenic yeasts, each with a
      disruption of one or several SAP genes. We focused on the construction of a C.
      albicans strain in which three related SAP genes (SAP4, SAP5, and SAP6) were
      disrupted. Growth of the delta sap4,5,6 triple homozygous null mutant DSY459 in
      complex medium was not affected, whereas, interestingly, growth in a medium
      containing protein as the sole nitrogen source was severely impaired compared to
      the growth of the wild-type parent strain SC5314. Since the presence of Sap2 is
      required for optimal growth on such medium, this suggests that Sap4, Sap5, or
      Sap6 plays an important role for the process of induction of SAP2. When guinea
      pigs and mice were injected intravenously with DSY459, their survival time was
      significantly longer than that of control animals infected with the wild-type
      SC5314. Attenuated virulence of DSY459 was followed by a significant reduction of
      yeast cells in infected organs. These data suggest that the group of Sap4, Sap5,
      and Sap6 isoenzymes is important for the normal progression of systemic infection
      by C. albicans in animals.

PMID- 9284118
TI  - Characterization of two virulence proteins secreted by rabbit enteropathogenic
      Escherichia coli, EspA and EspB, whose maximal expression is sensitive to host
      body temperature.
AB  - Enteropathogenic Escherichia coli (EPEC) and rabbit EPEC (RDEC-1) cause unique
      histopathological features on intestinal mucosa, including attaching/effacing
      (A/E) lesions. Due to the human specificity of EPEC, RDEC-1 has been used as an
      animal model to study EPEC pathogenesis. At least two of the previously
      identified EPEC-secreted proteins, EspA and EspB, are required for triggering
      host epithelial signal transduction pathways, intimate adherence, and A/E
      lesions. However, the functions of these secreted proteins and their roles in
      pathogenesis have not been characterized. To investigate the function of EspA and
      EspB in RDEC-1, the espA and espB genes were cloned and their sequences were
      compared to that of EPEC O127. The EspA proteins showed high similarity (88.5%
      identity), while EspB was heterogeneous in internal regions (69.8% identity).
      However, RDEC-1 EspB was identical to that of enterohemorrhagic E. coli serotype
      O26. Mutations in RDEC-1 espA and espB revealed that the corresponding RDEC-1
      gene products are essential for triggering of host signal transduction pathways
      and invasion into HeLa cells. Complementation with plasmids containing EPEC espA
      or/and espB genes into RDEC-1 mutant strains demonstrated that they were
      functionally interchangeable, although the EPEC proteins mediated higher levels
      of invasion. Furthermore, maximal expression of RDEC-1 and EPEC-secreted proteins
      occurred at their respective host body temperatures, which may contribute to the
      lack of EPEC infectivity in rabbits.

PMID- 9284119
TI  - Relevance of immunoglobulin G Fc receptor polymorphism to recurrence of adult
      periodontitis in Japanese patients.
AB  - Polymorphonuclear neutrophil (PMN) phagocytic function has been shown to be
      impaired in some patients with periodontitis. PMN constitutively express members
      of two immunoglobulin G receptor (Fc gammaR) classes: Fc gammaRIIa (CD32) and Fc
      gammaRIIIb (CD16). Both receptors exhibit genetically determined structural and
      functional biallelic polymorphisms, which have been shown to influence PMN
      phagocytic function. In this study, we assessed the relevance of these Fc gammaR
      polymorphisms to susceptibility to adult periodontitis and recurrence rate. The
      distribution of Fc gammaRIIa and Fc gammaRIIIb genotypes of 100 Japanese patients
      with adult periodontitis during follow-up was compared to the distribution of
      genotypes in 105 race-matched healthy controls. No significant skewing of
      distributions of Fc gammaRIIa and Fc gammaRIIIb genotypes was observed between
      patients and controls. Notably, however, a significant overrepresentation of the
      Fc gammaRIIIb-NA2 allotype was found in patients with disease recurrence (P <
      0.05; odds ratio, 4.29; 95% confidence interval, 1.19 to 16.24). Moreover, the
      annual rate of recurrence was significantly higher in patients with the Fc
      gammaRIIIb-NA2/NA2 and Fc gammaRIIIb-NA1/NA2 genotypes than in Fc gammaRIIIb
      NA1/NA1 individuals (P < 0.05). Fc gammaRIIa-R/R131 individuals also exhibited
      higher recurrence rates, though the difference was not statistically significant
      (P = 0.06). These results suggest that the Fc gammaRIIIb-NA2 allotype represents
      a risk factor for recurrence of adult periodontitis.

PMID- 9284120
TI  - Bacteroides fragilis toxin exhibits polar activity on monolayers of human
      intestinal epithelial cells (T84 cells) in vitro.
AB  - Strains of Bacteroides fragilis associated with diarrhea in children (termed
      enterotoxigenic B. fragilis, or ETBF) produce a heat-labile ca. 20-kDa protein
      toxin (BFT). The purpose of this study was to examine the activity of BFT on
      polarized monolayers of human intestinal epithelial cells (T84 cells). In Ussing
      chambers, BFT had two effects. First, BFT applied to either the apical or
      basolateral surfaces of T84 monolayers diminished monolayer resistance. However,
      the time course, magnitude, and concentration dependency differed when BFT was
      applied to the apical versus basolateral membranes. Second, only basolateral BFT
      stimulated a concentration-dependent and short-lived increase in short circuit
      current (Isc; indicative of C1- secretion). Time course experiments indicated
      that Isc returned to baseline as resistance continued to decrease, indicating
      that these two electrophysiologic responses to BFT are distinct. Light
      microscopic studies of BFT-treated monolayers revealed only localized cellular
      changes after apical BFT, whereas basolateral BFT rapidly altered the morphology
      of nearly every cell in the monolayer. Transmission and scanning electron
      microscopy after basolateral BFT confirmed a striking loss of cellular microvilli
      and complete dissolution of some tight junctions (zonula occludens) and zonula
      adherens without loss of desmosomes. The F-actin structure of BFT-treated
      monolayers (stained with rhodamine-phalloidin) revealed diminished and
      flocculated staining at the apical tight junctional ring and thickening of F
      actin microfilaments in focal contacts at the basolateral monolayer surface
      compared to those in similarly stained control monolayers. BFT did not injure T84
      monolayers, as assessed by lactic dehydrogenase release and protein synthesis
      assays. These studies indicate that BFT is a nonlethal toxin which acts in a
      polar manner on T84 monolayers to stimulate C1- secretion and to diminish
      monolayer resistance by altering the apical F-actin structure of these cells. BFT
      may contribute to diarrheal disease associated with ETBF infection by altering
      epithelial barrier function and stimulating C1- secretion.

PMID- 9284121
TI  - Comparison of immune responses in patients infected with Vibrio cholerae O139 and
      O1.
AB  - Vibrio cholerae O139 has recently emerged as the second etiologic agent of
      cholera in Asia. A study was carried out to evaluate the induction of specific
      immune responses to the organism in V. cholerae O139-infected patients. The
      immune responses to V. cholerae O139 Bengal were studied in patients by measuring
      antibody-secreting cells (ASC), as well as vibriocidal and antitoxic antibodies
      in the circulation. These responses were compared with those in patients with V.
      cholerae O1 disease. Strong immunoglobulin A (IgA) and IgM ASC responses were
      seen against the homologous lipopolysaccharide or serogroup of V. cholerae. The
      magnitude and isotype of the responses were similar in O139- and O1-infected
      patients. Vibriocidal antibody responses were seen against bacteria of the
      homologous but not heterologous serogroup, and these responses reflect the lack
      of cross-protection between the infections caused by the two serogroups. The two
      groups of patients showed comparable cholera toxin-specific ASC responses, with
      the IgG isotype dominating over the IgA isotype, as well as comparable antitoxic
      immune responses in plasma. These results suggest that despite having a
      polysaccharide capsule, V. cholerae O139 induces systemic and intestine-derived
      ASC responses in peripheral blood comparable to those seen in patients with V.
      cholerae O1 disease.

PMID- 9284122
TI  - Serum factors, cell membrane CD14, and beta2 integrins are not required for
      activation of bovine macrophages by lipopolysaccharide.
AB  - The role of serum factors such as lipopolysaccharide (LPS)-binding protein (LBP)
      and of macrophage-expressed CD14 and beta2 integrins in the activation of bovine
      macrophages by LPS was investigated. Macrophage activation was determined by
      measuring tumor necrosis factor production, NO generation, and upregulation of
      procoagulant activity by LPS (Escherichia coli O55:B5) at concentrations of 100
      pg/ml to 100 ng/ml. The 50% effective dose for LPS was 1 order of magnitude
      higher than that for activating human macrophages. Macrophages were activated by
      LPS in the presence of serum or in the presence of albumin demonstrated to be
      free of LBP. The capacity to react to LPS in the absence of LBP was not due to
      the acquisition of LBP during a previous culture in serum. It was then
      established which CD14-specific antibodies block LPS binding to monocytes. Among
      the CD14-specific antibodies recognizing bovine mononuclear phagocytes (60bca,
      3C10, My4, CAM36, VPM65, CMRF31, and TUK4), the first four blocked the binding of
      LPS-fluorescein isothiocyanate to bovine monocytes at low concentrations. Anti
      CD14 antibodies did not block LPS-mediated activation of bovine bone marrow
      derived macrophages, monocyte-derived macrophages, and alveolar macrophages. This
      was observed in experiments in which anti-CD14 concentrations exceeded the 50%
      inhibitory dose by >30-fold (3C10 and My4) or >300-fold (60bca), as defined in
      the binding assay described above. Monocyte-derived macrophages from an animal
      deficient in beta2 integrins and control macrophages were activated by similar
      concentrations of LPS, suggesting that beta2 integrins are not important bovine
      LPS receptors. Thus, in bovine macrophages, LPS recognition pathways which are
      independent of exogenous LBP, of membrane-expressed CD14, and of beta2 integrins
      may exist.

PMID- 9284123
TI  - Evolutionary genetics of Pasteurella haemolytica isolates recovered from cattle
      and sheep.
AB  - Genetic diversity and relationships among 194 Pasteurella haemolytica isolates,
      which were recovered predominantly from cattle (39%) and sheep (58%) suffering
      from pneumonic pasteurellosis in the United Kingdom, Germany, and the United
      States, were estimated by examination of allelic variation at 18 enzyme-encoding
      loci detected by multilocus enzyme electrophoresis. The isolates formed two major
      divisions. One included 178 Pasteurella haemolytica sensu stricto strains
      representing serotypes A1, A2, A5 to A9, A12 to A14, and A16; the other was
      composed of 16 isolates belonging to the A11 taxon. P. haemolytica isolates were
      classified into 22 electrophoretic types (ETs) that formed three primary
      phylogenetic lineages. One lineage was represented by ovine serotype A2 isolates,
      a second lineage consisted of bovine serotype A2, together with serotype A7 and
      A13 isolates, and the third lineage included isolates representing all of the
      other serotypes, as well as a second group of serotype A7 strains.
      Electrophoretic types were nonrandomly associated with specific capsular
      serotypes, lipopolysaccharide (LPS) types, outer membrane protein (OMP) types,
      and host species. Bovine isolates were represented by only three serotypes (A1,
      A2, and A6) in 5 ETs, whereas ovine isolates were represented by all of the
      serotypes in 19 ETs. The majority (76%) of bovine isolates were of serotypes A1
      or A6 and belonged to a single ET that marked a virulent, cattle-specific clonal
      group. Among the ovine isolates, 40% were of serotype A2 and belonged to two ETs
      that represented two virulent, sheep-specific clonal groups. Bovine A1 and A6
      isolates and bovine A2 isolates were phylogenetically distinct from ovine
      isolates of the same serotypes, indicating that different subpopulations of these
      serotypes are associated with disease in cattle and sheep. Consistent differences
      in the OMP profiles of strains of the bovine and ovine lineages of these three
      serotypes suggest that certain OMPs are involved in host specificity and
      virulence. Evolutionary relationships among P. haemolytica isolates indicate that
      the ancestral host is the sheep and that several distinct clonal lineages have
      crossed the species barrier into cattle. The A11 taxon is a heterogeneous group
      of opportunistic pathogens of sheep that represents a separate species.

PMID- 9284124
TI  - Interleukin-12 (IL-12) and IL-18 synergistically induce the fungicidal activity
      of murine peritoneal exudate cells against Cryptococcus neoformans through
      production of gamma interferon by natural killer cells.
AB  - We examined the ability of interleukin-12 (IL-12) and IL-18 to induce the
      production of gamma interferon (IFN-gamma) and nitric oxide (NO) by murine
      peritoneal exudate cells (PEC) and to stimulate the growth-inhibitory activity of
      these cells against Cryptococcus neoformans. PEC produced IFN-gamma and NO when
      stimulated with a combination of IL-12 and IL-18 but little or no IFN-gamma or NO
      when either cytokine was used alone. PEC anticryptococcal activity was mediated
      by IFN-gamma and NO production, since it was completely inhibited by a
      neutralizing anti-IFN-gamma monoclonal antibody (MAb) and N(G)-monomethyl-L
      arginine, a competitive inhibitor of NO synthesis, respectively. To identify the
      IFN-gamma-producing cells among PEC stimulated with IL-12 and IL-18, we depleted
      NK cells, gammadelta T cells, or CD4+ T cells by treating PEC with specific Abs
      and complement. NK cell depletion strongly suppressed IFN-gamma production and
      almost completely inhibited NO production and anticryptococcal activity, while
      depletion of other cells had no such influence. Alternatively, purified NK cells
      by two cycles of glass adherence and magnetic separation with anti-CD3, -CD4, 
      CD8, and -B220 MAbs produced a greater amount of IFN-gamma by stimulation with IL
      12 and IL-18 than unseparated non-glass-adherent PEC. Our results demonstrated
      that IL-12 and IL-18 synergistically induced NO-dependent anticryptococcal
      activity of PEC by stimulating NK cells to produce IFN-gamma.

PMID- 9284125
TI  - Comparison of the sequences and functions of Streptococcus equi M-like proteins
      SeM and SzPSe.
AB  - Streptococcus equi (Streptococcus equi subsp. equi), a Lancefield group C
      streptococcus, causes strangles, a highly contagious purulent lymphadenitis and
      pharyngitis of members of the family Equidae. The antiphagocytic 58-kDa M-like
      protein SeM is a major virulence factor and protective antigen. The amino acid
      sequence and structure of SeM has been determined and compared to that of a
      second, 40-kDa M-like protein (SzPSe) of S. equi and to those of other
      streptococcal proteins. Both SeM and SzPSe are mainly alpha-helical fibrillar
      molecules with no homology other than that between their signal and membrane
      anchor sequences and are only distantly related to other streptococcal M and M
      like proteins. The sequence of SzPSe indicates that it is an allele of SzP that
      encodes the variable protective M-like and typing antigens of S. zooepidemicus
      (S. equi subsp. zooepidemicus). SeM is opsonogenic for S. equi but not for the
      closely related S. zooepidemicus, whereas SzPSe is strongly opsonogenic for S.
      zooepidemicus but not for S. equi. Both proteins bind equine fibrinogen. SeM and
      SzPSe proteins from temporally and geographically separated isolates of S. equi
      are identical in size. The results taken together support previous evidence that
      S. equi is a clonal pathogen originating from an ancestral strain of S.
      zooepidemicus. We postulate that acquisition of SeM synthesis was a key element
      in the success of the clone because of its effect in enhancing resistance to
      phagocytosis and because protective immunity entails a requirement for SeM
      specific antibody.

PMID- 9284127
TI  - Necrosis versus apoptosis as the mechanism of target cell death induced by
      Entamoeba histolytica.
AB  - The human pathogen Entamoeba histolytica is known to kill a variety of host
      cells, including leukocytes. Using human myeloid cells as targets, we studied
      whether cytotoxicity of amoebic trophozoites in vitro is equivalent to the
      induction of apoptosis or whether these target cells die via necrosis. Based upon
      morphological criteria, incubation of target cells with amoebae resulted in
      necrosis, with cell swelling, rupture of plasma membrane, and release of cell
      contents including nucleic acids being detected by light and transmission
      electron microscopy. On the other hand, the characteristic features of apoptosis
      such as cell shrinking, surface blebbing, and chromatin condensation were not
      observed. Moreover, internucleosomal fragmentation of genomic DNA within target
      cells as a characteristic feature of apoptotic cell death did not occur as judged
      by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling
      technique in combination with flow cytometry. Consistently, cleavage of DNA was
      detectable upon agarose gel electrophoresis only after a substantial part of the
      target cell population had already been lysed. We also analyzed the mechanism of
      cell death induced by amoebapores, pore-forming peptides and primary candidate
      molecules for mediating the cytolytic activity of E. histolytica. At a time point
      at which the majority of target cells showed membrane injury upon incubation with
      purified amoebapores, no DNA degradation was detectable in the victim cells. The
      data suggest that the target cells used in our study undergo necrosis rather than
      apoptosis when they are killed by viable trophozoites as well as by isolated
      amoebapores.

PMID- 9284126
TI  - Analysis of expression of the alpha-toxin gene (hla) of Staphylococcus aureus by
      using a chromosomally encoded hla::lacZ gene fusion.
AB  - The staphylococcal alpha-toxin (Hla) is a major virulence factor contributing to
      Staphylococcus aureus pathogenesis. To elucidate the conditions influencing hla
      expression, the determinant was fused to lacZ, the reporter gene coding for beta
      galactosidase. The hla::lacZ fusion was integrated into the chromosome of the
      wild-type S. aureus strain Wood 46, leading to the variant Wood 46-3. Alpha-toxin
      expression was found to be dependent on temperature, showing a maximum at 42
      degrees C. Furthermore, the indicator strain showed a growth phase-dependent hla
      regulation which was influenced by temperature. At 37 degrees C, induction of
      hla::lacZ expression occurred in the late exponential phase of growth, whereas at
      42 degrees C, a strong induction was observed as early as the mid-exponential
      phase. These observations were verified by Northern blot analysis of hla mRNA and
      by Western blot (immunoblot) analysis of culture supernatants of strain Wood 46.
      It was additionally found that the induction of hla transcription at 42 degrees C
      was not coupled with higher concentrations of agr RNAIII, the effector molecule
      of the global regulator agr. Furthermore, expression of the alpha-toxin was
      repressed at a high osmolarity. It was also shown that oxygen is essential for
      hla expression and that cultivation of the S. aureus strain Wood 46-3 on solid
      medium and in the presence of carbon dioxide stimulated hla transcriptional
      activity.

PMID- 9284129
TI  - Baculovirus-mediated expression of Plasmodium falciparum erythrocyte binding
      antigen 175 polypeptides and their recognition by human antibodies.
AB  - The erythrocyte binding antigen EBA-175 is a 175-kDa Plasmodium falciparum
      protein which mediates merozoite invasion of erythrocytes in a sialic acid
      dependent manner. The purpose of this study was to produce recombinant EBA-175
      polypeptide domains which have previously been identified as being involved in
      the interaction of EBA-175 with erythrocytes and to determine whether these
      polypeptides are recognized by malaria-specific antibodies. The eba-175 gene was
      cloned by PCR from genomic DNA isolated from the 3D7 strain of P. falciparum. The
      predicted protein sequence was highly conserved with that predicted from the
      published eba-175 gene sequences from the Camp and FCR-3 strains of P. falciparum
      and contained the F segment divergent region. Purified recombinant EBA-175
      polypeptide fragments, expressed as glutathione S-transferase fusion proteins in
      insect cells by using the baculovirus system, were recognized by antibodies
      present in serum from a drug-cured, malaria-immune Aotus nancymai monkey. The
      fusion proteins were also recognized by antibodies present in sera from
      individuals residing in areas where malaria is endemic. In both cases the
      antibodies specifically recognized the EBA-175 polypeptide portion of the fusion
      proteins. Antibodies raised in rabbits immunized with the recombinant fusion
      proteins recognized parasite proteins present in schizont-infected erythrocytes.
      Our results suggest that these regions of the EBA-175 protein are targets for the
      immune response against malaria and support their further study as possible
      vaccine components.

PMID- 9284128
TI  - Role of adherence in interleukin-8 induction in Helicobacter pylori-associated
      gastritis.
AB  - Active Helicobacter pylori-associated gastritis is characterized by a dense
      mucosal infiltration with granulocytes. Since H. pylori is noninvasive, secondary
      signals must induce the accumulation of granulocytes. Interleukin-8 (IL-8) has
      been shown to play a key role in this event. Using competitive reverse
      transcriptase-PCR on mRNA from gastric biopsies, we could show a clear
      correlation between the amount of IL-8 transcripts and the activity of H. pylori
      gastritis. Due to the inability of the bacterium to invade host cells, the
      epithelial layer is a potential candidate as an IL-8 source. To study the
      mechanism of IL-8 induction, established gastric carcinoma epithelial cell lines
      (AGS and Kato III) and well-defined H. pylori strains were used in a modified in
      vitro system. The experimental design enabled us to prevent direct contact of
      bacteria with epithelial cells by use of a filter membrane which did not block
      secreted bacterial products crossing the membrane. The data clearly showed that
      the direct contact of the bacterial cell with the epithelial cell is necessary
      for optimal IL-8 production because not only live bacteria, but also
      metabolically inactive bacteria, increased IL-8 secretion. Neither purified
      lipopolysaccharide nor water-soluble protein fractions of H. pylori NCTC 11637
      and Tx30a nor the cytotoxin of H. pylori was able to increase IL-8 production
      significantly by the epithelial cells used. Furthermore, preparations of total
      membrane and outer membrane proteins of H. pylori were not able to stimulate IL-8
      release in vitro. Accumulatively, these results imply that active metabolism is
      not necessary for stimulation as long as there is an intact membrane aiding the
      presentation of a stimulating membrane complex or aggregate on the surface of the
      bacteria. From these results, we conclude that whole bacteria and their direct
      contact with epithelial cells may be critical for IL-8 induction in vivo.

PMID- 9284130
TI  - Bordetella pertussis binds the human complement regulator C4BP: role of
      filamentous hemagglutinin.
AB  - C4BP (C4b-binding protein) is a high-molecular-weight plasma protein that
      inhibits the classical pathway of complement activation. Recent experiments have
      demonstrated that C4BP binds to many strains of the gram-positive bacterium
      Streptococcus pyogenes, a major respiratory tract pathogen. Binding to S.
      pyogenes was shown to be due to members of the M protein family, a group of
      surface proteins important for virulence. Here we report that human C4BP also
      binds to all clinical isolates of the gram-negative bacterium Bordetella
      pertussis, the etiologic agent of whooping cough. In addition, binding of C4BP
      was demonstrated for other Bordetella species that can cause disease in humans.
      Characterization of different B. pertussis mutants showed that the binding of
      C4BP is strongly dependent on the expression of the cell surface protein
      filamentous hemagglutinin, a well-known virulence factor. Inhibition experiments
      suggested that B. pertussis and S. pyogenes bind to the same region in C4BP. The
      finding that B. pertussis and S. pyogenes both have the ability to bind human
      C4BP suggests that these two unrelated respiratory tract pathogens may use a
      common mechanism during the establishment of an infection.

PMID- 9284131
TI  - Mechanism of nitric oxide-dependent killing of Mycobacterium bovis BCG in human
      alveolar macrophages.
AB  - We demonstrated that products of the L-arginine-dependent pathway of human
      alveolar macrophages (AM) effectively kill the Mycobacterium bovis bacillus
      Calmette-Guerin (BCG) in vitro. The formation of products was triggered by
      inoculation with BCG itself. Many reports have shown that activated rodent AM
      could produce an amount of nitric oxide (NO) sufficient to suppress the growth of
      mycobacteria. However, there have been no definitive results as to whether human
      AM might have the NO-dependent mechanism for the killing of mycobacteria.
      Therefore, we have undertaken some experiments to answer this question.
      Immunofluorescence assays showed an increased production of inducible nitric
      oxide synthase (iNOS) and peroxynitrite in BCG-inoculated AM from patients with
      pulmonary fibrosis. Reverse transcriptase-PCR also revealed the higher expression
      of iNOS-coding mRNA. Colony assays demonstrated that these human AM effectively
      killed BCG in their cytoplasm. However, treatment of AM with N(G)-monomethyl-L
      arginine monoacetate resulted in markedly reduced killing activity. These results
      clearly show that BCG-induced NO and its reactive product with the oxygen radical
      peroxynitrite could play an important role in the killing of BCG in human AM.

PMID- 9284132
TI  - Specificity and functional activity of anti-Burkholderia pseudomallei
      polysaccharide antibodies.
AB  - The lipopolysaccharide (LPS) of Burkholderia pseudomallei, the causative agent of
      melioidosis, consists of two O-antigenic polysaccharides designated O-PS I and O
      PS II. In this study, the O-PS specificity and functional activity of a
      protective polyclonal antiserum and an immunoglobulin M (IgM) monoclonal antibody
      were determined. The polyclonal antiserum recognized both O-PS I and O-PS II,
      while the monoclonal antibody was O-PS II specific. Both mediated phagocytic
      killing of B. pseudomallei by polymorphonuclear leukocytes. Patients acutely
      infected with B. pseudomallei also produced antibodies to the two O-PSs, but
      these antibodies were not produced by asymptomatic individuals from an area of
      endemicity who were seropositive by an indirect hemagglutination test using
      sonicated heat-killed whole organisms as antigen. IgM antibodies were detected
      only in patients with localized infection. IgG antibodies were detected in all
      acutely infected patients, but there was no significant difference in antibody
      levels among patients with localized infection, patients who survived septicemic
      illness, and patients who died from septicemic illness. Further analysis of the
      IgG response revealed production of IgG1 and IgG2 antibodies by all patient
      groups, while an IgG3 response was seen only in survivors of septicemic
      infection. IgG4 was not detectable even when a fivefold-lower serum dilution was
      used. Patient sera also mediated phagocytic killing by polymorphonuclear
      leukocytes, and the killing effect was enhanced by complement. These results
      suggest that antibodies to the LPS O-polysaccharides of B. pseudomallei are
      protective by promoting phagocytic killing. The antibodies develop during human
      infection and may facilitate clearance of the organisms, as seen in a diabetic
      rat model of B. pseudomallei infection.

PMID- 9284134
TI  - Vibrio mimicus attaches to the intestinal mucosa by outer membrane hemagglutinins
      specific to polypeptide moieties of glycoproteins.
AB  - Vibrio mimicus is the closest organism to Vibrio cholerae. V. mimicus E-33, which
      is a highly adhesive and enteropathogenic strain, is known to produce three types
      of hemagglutinins (HAs), i.e., a 31-kDa exocellular metalloprotease (Vm
      HA/protease), lipopolysaccharide (Vm-LPSHA), and a 39-kDa major outer membrane
      protein (Vm-OMPHA). Hemagglutination induced by Vm-LPSHA and Vm-OMPHA was
      inhibited by glycoproteins, including mucin, fetuin, and asialofetuin, but not by
      monosaccharides, disaccharides, or N-acetylated saccharides. The inhibitory
      potential of each glycoprotein for Vm-OMPHA was greatly augmented by treatment
      with a glycolytic enzyme such as beta-D-galactosidase or beta-D-glucosidase,
      while pronase treatment achieved complete abolition of the inhibitory potential.
      The inhibitory ability of the glycoproteins for Vm-LPSHA was also abolished by
      pronase treatment; however, glycolytic enzyme treatment showed no effect. Hence,
      the polypeptide portion of glycoproteins may directly associate with Vm-OMPHA and
      Vm-LPSHA, but the sugar moiety may act as a barrier to interaction with Vm-OMPHA.
      The glycoproteins as well as Fab antibodies against Vm-OMPHA and Vm-LPSHA
      eliminated the ability of E-33 cells to agglutinate rabbit erythrocytes and to
      attach to rabbit intestinal mucosa. Additionally, expression of the
      hemagglutinating ability by the bacterial cells was accompanied by efficient
      bacterial adherence to the intestinal mucosa. Finally, the hemagglutinating
      activity of Vm-OMPHA was markedly increased by incubation with Vm-HA/protease.
      These results indicate that all three HAs may have significant roles in the
      glycoprotein-mediated intestinal adherence of V. mimicus E-33.

PMID- 9284133
TI  - The Oms66 (p66) protein is a Borrelia burgdorferi porin.
AB  - In this study we report the purification and characterization of a 66-kDa
      protein, designated Oms66, for outer membrane-spanning 66-kDa protein, that
      functions as a porin in the outer membrane (OM) of Borrelia burgdorferi. Oms66
      was purified by fast-performance liquid chromatography and exhibited an average
      single-channel conductance of 9.62 +/- 0.37 nS in 1 M KCl, as evidenced by 581
      individual insertional events in planar lipid bilayers. Electrophysiological
      characterization indicated that Oms66 was virtually nonselective between cations
      and anions and exhibited voltage-dependent closure with multiple substates. The
      amino acid sequence of tryptic peptides derived from purified Oms66 was identical
      to the deduced amino acid sequence of p66, a previously described surface-exposed
      protein of B. burgdorferi. Purified Oms66 was recognized by antiserum specific
      for p66 and serum from rabbits immune to challenge with virulent B. burgdorferi,
      indicating that p66 and Oms66 were identical proteins and that Oms66/p66 is an
      immunogenic protein in infected rabbits. In a methodology that reduces liposomal
      trapping and nonspecific interactions, native Oms66 was incorporated into
      liposomes, confirming that Oms66 is an outer membrane-spanning protein.
      Proteoliposomes containing Oms66 exhibited porin activity nearly identical to
      that of native, purified Oms66, indicating that reconstituted Oms66 retained
      native conformation. The use of proteoliposomes reconstituted with Oms66 and
      other Oms proteins provides an experimental system for determinating the
      relationship between conformation, protection, and biological function of these
      molecules.

PMID- 9284135
TI  - Antigenic heterogeneity and molecular analysis of CopB of Moraxella (Branhamella)
      catarrhalis.
AB  - Outer membrane protein (OMP) CopB, an iron-repressible 81-kDa major OMP of
      Moraxella (Branhamella) catarrhalis has been a major focus of investigation. To
      assess CopB as a potential vaccine antigen, we elucidated the degree of antigenic
      and sequence heterogeneity in this protein among strains of M. catarrhalis. Two
      monoclonal antibodies, 1F5 and 2.9F, which bind to surface-exposed epitopes on
      CopB recognized 60 and 70% of the strains, respectively. The degree of sequence
      heterogeneity in CopB was assessed by cloning and sequencing the CopB gene from
      two different strains of M. catarrhalis and comparing with the published
      sequence. There was 92 to 96% homology between the sequences at the nucleotide
      level and 90 to 95% homology at the amino acid level. The variability in the
      protein sequence is confined mainly to three moderately variable regions.
      Restriction fragment length polymorphism (RFLP) analysis of the CopB genes
      obtained from 20 diverse strains by PCR was performed. Ninety percent of the
      potential restriction sites in the constant regions and 47% of the potential
      restriction sites in the variable regions were present in the 20 strains,
      indicating that the pattern of variable and constant areas in the CopB gene is a
      general pattern among strains of M. catarrhalis. We conclude that the CopB gene
      is largely conserved among strains of M. catarrhalis and contains discrete
      regions which show moderate heterogeneity among strains.

PMID- 9284136
TI  - Coccoid forms of Helicobacter pylori are the morphologic manifestation of cell
      death.
AB  - Helicobacter pylori can transform from its normal helical bacillary morphology to
      a coccoid morphology. Since this coccoid form cannot be cultured in vitro, it has
      been speculated that it is a dormant form potentially involved in the
      transmission of H. pylori and in a patient's relapse after antibiotic therapy. In
      this study we determined the effects of aging, temperature, aerobiosis,
      starvation, and antibiotics on the morphologic conversion rate and culturability
      of H. pylori. Aerobiosis and the addition of a bactericidal antibiotic to the
      culture medium resulted in the highest conversion rate. During the conversion to
      coccoid forms, the cultures always lost culturability at the stage where 50% of
      the organisms were still in bacillary form; this result indicated that
      culturability and coccoid morphology are two separate but related entities.
      Independent of the conditions used to induce the conversion into coccoids, the
      morphological conversion was accompanied by several marked antigenic and
      ultrastructural changes. Also, both the total amounts and the integrity of RNA
      and DNA were significantly reduced in coccoid forms. With the potential-sensitive
      probe diOC(5)-3, a clear loss of membrane potential in coccoid forms was
      observed. Inhibition of protein or RNA synthesis by the addition of
      bacteriostatic antibiotics did not prevent the conversion to coccoid forms but
      resulted in an increased conversion rate. Hence, we conclude that conversion of
      H. pylori from the bacillary to the coccoid form is a passive process that does
      not require protein synthesis. Our data suggest that the coccoid form of H.
      pylori is the morphologic manifestation of bacterial cell death.

PMID- 9284138
TI  - Virulence plasmid instability in Shigella flexneri 2a is induced by virulence
      gene expression.
AB  - Expression of the predominantly plasmid-encoded virulence regulon of Shigella
      flexneri 2a is induced by growth at 37 degrees C and repressed by growth at 30
      degrees C. During growth at 37 degrees C, spontaneous S. flexneri mutants arise
      which have undergone virulence plasmid curing or rearrangement and no longer
      display the virulent phenotype. In the laboratory, the unstable nature of the
      virulence plasmid causes complete loss of virulence in a growing population. We
      have undertaken an analysis of virulence plasmid instability, classifying events
      which produced individual avirulent derivatives within a virulent population and
      identifying the factor(s) which controlled conversion. Multiplex PCR analysis of
      DNA obtained from spontaneous avirulent derivatives indicated that virF and virB
      were deleted or otherwise inactivated in over 97% of the isolates. The virF and
      virB loci encode regulatory proteins required for transcriptional activation of
      the virulence regulon. Inactivation of these key regulatory loci in the vast
      majority of avirulent derivatives which arose during growth at 37 degrees C
      suggested that virulence gene expression induced virulence plasmid instability.
      Consistent with this hypothesis, we observed stable virulence plasmid maintenance
      during growth of a wild-type strain at 30 degrees C where virulence gene
      expression was repressed. The virulence plasmid was also stably maintained in
      virF and virB mutants grown at 37 degrees C. Conversely, virulence plasmid
      destabilization was induced at 30 degrees C and accelerated at 37 degrees C
      through expression of VirF or VirB from multicopy plasmids. These results
      indicate that exposure of S. flexneri to conditions favoring induction of the
      virulent phenotype also favor its loss. The significance of this paradox of
      Shigella pathogenicity is discussed.

PMID- 9284139
TI  - Pathogenicity of three strains of Serpulina pilosicoli in pigs with a naturally
      acquired intestinal flora.
AB  - Serpulina pilosicoli is an anaerobic spirochete which has been isolated from the
      colons of pigs with enteric disease. The clinical and pathologic features of
      experimental infections of conventional pigs (born by normal farrowing with a
      naturally acquired intestinal flora) with three strains of S. pilosicoli were
      determined in order to confirm the enteropathogenicity of this species. Strains
      were derived from the colons of British pigs with colitis and passaged 8 to 10
      times during expansion and purification in vitro. Eighteen ten-week-old Large
      White-Landrace cross pigs were each inoculated once orally with 0.7 x 10(9) to
      1.6 x 10(9) of one of three strains of S. pilosicoli. Six pigs were challenged
      with each strain. Control pigs were dosed with uninfected broth medium or with
      1.8 x 10(7) cells of the nonpathogenic Serpulina innocens. Eight pigs (two to
      four per S. pilosicoli challenge group) developed soft or diarrheic feces (fecal
      dry matter < 24%) between 3 and 8 days after challenge, which persisted for 7 to
      8 days or until necropsy at 14 days after challenge. Average weight gains in two
      of the three groups challenged with S. pilosicoli were significantly less than
      controls. The feed conversion ratios of all the groups challenged with S.
      pilosicoli were impaired compared to controls. The mean values for daily
      liveweight gain (and feed conversion ratio) for the three groups challenged with
      S. pilosicoli were 0.799 (2.13), 0.783 (2.05), and 0.844 kg (2.10), respectively,
      while that of the uninoculated controls was 0.944 kg (1.70). Gross lesions with
      slight mucosal thickening, congestion, and multifocal erosions were evident in
      seven of eight diarrheic pigs. The relative weights of the large intestines of
      pigs challenged with S. pilosicoli were significantly less than controls.
      Histologic lesions with an increase in mucosal height, infiltration of the lamina
      propria with mononuclear cells, mucosal erosion with mixed inflammatory cell
      infiltration, and goblet cell hyperplasia in colonic glands were evident in 15 of
      the 18 challenged pigs. S. pilosicoli was recovered on bacterial culture of the
      colon from all except one of the pigs with these histologic lesions. Serpulina
      sp. was clearly visible within the colonic glands of these affected pigs in
      silver-stained sections of the gut. Clinical and pathologic findings in control
      pigs were unremarkable, with no diarrhea or colonic lesions evident. The results
      provide further evidence that S. pilosicoli is a specific enteric pathogen for
      conventional pigs. It is capable of colonizing the large intestine and causing
      mucosal damage, which although mild is sufficient to result in significant
      adverse effects on growth.

PMID- 9284137
TI  - Analysis of the genes encoding the antigen 85 complex and MPT51 from
      Mycobacterium avium.
AB  - The components of the fibronectin-binding antigen 85 complex (85A, 85B, and 85C)
      and the related protein MPB/MPT51 are major secreted proteins in Mycobacterium
      tuberculosis and Mycobacterium bovis BCG. The fbpA, fbpC, and mpt51 genes
      encoding 85A, 85C, and MPT51, respectively, were isolated from Mycobacterium
      avium and sequenced in this study. The structures of these genes, and that of the
      fbpB gene encoding the 85B protein, were conserved in these three species. The
      secreted amounts of 85A, 85B, 85C, and MPB/MPT51 were compared for M.
      tuberculosis, BCG, and M. avium. These four proteins were found in large amounts
      in the culture filtrates from M. tuberculosis and BCG. In contrast, in the
      culture filtrate from M. avium, 85B and MPT51 were abundant whereas 85A and 85C
      were hardly found, in spite of the presence of the encoding genes. The difference
      in the secretion amounts might be regulated at the transcription level. These
      facts might reflect host immunopathogenesis, the protective immunities against
      infections, and the drug susceptibilities of these organisms.

PMID- 9284140
TI  - Outer membrane protein D15 is conserved among Haemophilus influenzae species and
      may represent a universal protective antigen against invasive disease.
AB  - We have cloned and sequenced the d15 gene from two strains of Haemophilus
      influenzae type b (Hib) and two strains of nontypeable H. influenzae (NTHI). The
      nucleotide and deduced protein sequences of d15 are highly conserved, with only a
      small variable region identified near the carboxyl terminus of the protein.
      Analysis of upstream sequences revealed that the H. influenzae d15 gene may be
      part of a large potential operon of closely spaced open reading frames, including
      one with significant homology to the Escherichia coli cds gene encoding CDP
      diglyceride synthetase. Southern blot analysis demonstrated that the d15 gene is
      also present in H. influenzae types a, c, d, e, and f and in Haemophilus
      parainfluenzae. A recombinant D15 (rD15) protein was expressed in good quantity
      in E. coli from the inducible T7 promoter, and monospecific anti-rD15 antibodies
      were raised. Immunoblot analysis of H. influenzae serotypes a, b, c, d, e, and f,
      NTHI, and H. parainfluenzae lysates revealed that they all expressed a cross
      reactive D15-like protein. Purified rD15 was found to be highly immunogenic in
      mice, guinea pigs, and rabbits, and passive transfer of anti-rD15 antibodies
      protected infant rats from challenge with H. influenzae type b or type a in
      infant rat models of bacteremia. Thus, D15 is a highly conserved antigen that is
      protective in animal models and it may be a useful component of a universal
      subunit vaccine against Haemophilus infection and disease.

PMID- 9284141
TI  - Evidence for ethnic tropism of Helicobacter pylori.
AB  - Helicobacter pylori infection in humans is linked to gastritis, gastric and
      duodenal ulcers, and gastric cancer. Peptic ulcer disease, as distinct from
      chronic asymptomatic infection, is strongly associated with expression of
      bacterial virulence markers, including a major antigen, CagA, and the vacuolating
      cytotoxin VacA. We have previously described significant differences in
      colonization rates, independent of socioeconomic status, among ethnic groups in
      New Zealand. To evaluate relative risks for peptic ulcer disease, we examined the
      frequency of two virulence markers in H. pylori strains infecting these ethnic
      groups. Although these markers occurred significantly more frequently in strains
      isolated from Polynesians than in strains from Europeans, this frequency was not
      reflected in the incidence of peptic ulcer disease in the two groups. DNA
      fingerprinting of the urease gene showed that Polynesians are more frequently
      infected by a group of strains which are genetically distinct from those
      affecting European New Zealanders. Our data suggest that separate bacterial
      lineages may have evolved in parallel with race-specific specialization.

PMID- 9284142
TI  - Release of tumor necrosis factor alpha in response to Vibrio vulnificus capsular
      polysaccharide in in vivo and in vitro models.
AB  - Vibrio vulnificus produces a severe septic shock syndrome in susceptible
      individuals. Virulence of the bacterium has been closely linked to the presence
      of a surface-exposed acidic capsular polysaccharide (CPS). To investigate whether
      CPS plays an additional role in pathogenesis by modulating inflammatory
      associated cytokine production, studies were initiated in a mouse model and
      followed by investigations of cytokine release from human peripheral blood
      mononuclear cells (PBMCs). Mouse tumor necrosis factor alpha (TNF-alpha) could be
      detected in serum up to 12 h postinoculation in animals challenged with the
      encapsulated parent strain MO6-24/O. The unencapsulated strain CVD752 was quickly
      eliminated by the animals, thus preventing a direct association between serum TNF
      alpha levels and the presence or absence of the CPS. Purified CPS from MO6-24/O
      when injected into D-galactosamine-sensitized mice was a more immediate inducer
      of TNF-alpha than an equivalent quantity of MO6-24/O lipopolysaccharide (LPS).
      Both V. vulnificus CPS and V. vulnificus LPS induced inflammation-associated
      cytokine responses from primary human PBMCs in vitro. CPS elicited TNF-alpha from
      PBMCs in a dose-dependent manner, with maximal induction at 6 to 10 h, and was
      not inhibited by polymyxin B. Expression of interleukin-6 (IL-6) mRNAs was also
      induced in the presence of CPS. Interestingly, while adherent PBMCs secreted high
      levels of TNF-alpha after stimulation with LPS, they secreted little TNF-alpha in
      response to CPS. These studies provide evidence that V. vulnificus CPS directly
      stimulates the expression and secretion of proinflammatory cytokines by murine
      and human cells and suggest that CPS activation of PBMCs operates through a
      cellular mechanism distinct from that of LPS.

PMID- 9284143
TI  - Binding of Pasteurella haemolytica leukotoxin to bovine leukocytes.
AB  - Pasteurella haemolytica is the principal bacterial pathogen in the bovine
      respiratory disease complex. This organism produces an exotoxin (referred to as
      leukotoxin) during logarithmic-phase growth that is a potent leukocyte-modulating
      agent. At low concentrations, it activates neutrophils and mononuclear phagocytes
      to release inflammatory mediators, while at the same time making these cells
      destined to undergo apoptotic cell death. At higher concentrations, the toxin
      causes rapid swelling and loss of cell viability. In this study, we demonstrated
      that toxin binding can be directly evaluated by flow cytometry with biologically
      active biotinylated leukotoxin. Leukotoxin binding was blocked by the addition of
      a neutralizing anti-leukotoxin monoclonal antibody and was not detected when
      bovine leukocytes were incubated with culture filtrates from a mutant strain of
      P. haemolytica that does not produce biologically active leukotoxin. In addition,
      treatment of bovine leukocytes with protease K eliminated subsequent binding of
      leukotoxin, suggesting that there is a protein on the leukocyte surface that is
      either a leukotoxin binding site or is required for stabilization of leukotoxin
      binding. We did not detect binding of biotinylated leukotoxin to porcine or human
      leukocytes, which have been reported previously to be resistant to the lytic
      effects of the leukotoxin. These findings suggest that there may be a specific
      binding site for P. haemolytica leukotoxin on bovine but not on porcine or human
      leukocytes and that it might be involved in the activation and lytic activities
      of the leukotoxin.

PMID- 9284144
TI  - SlyA, a transcriptional regulator of Salmonella typhimurium, is required for
      resistance to oxidative stress and is expressed in the intracellular environment
      of macrophages.
AB  - Appropriate regulation of genes enables Salmonella typhimurium to adapt to the
      intracellular environment of the host. The Salmonella slyA gene is in a family of
      transcriptional regulators that may play an important role in this adaptation. We
      have previously shown that slyA mutant Salmonella strains are profoundly
      attenuated for virulence and do not survive in macrophages. In this study, we
      demonstrate that the expression of multiple Salmonella proteins is regulated by
      SlyA during stationary phase and during infection of macrophages. Both of these
      conditions also induced the expression of a slyA::lacZ transcriptional fusion.
      Expression of the slyA::lacZ transcriptional fusion increased 15-fold in
      stationary phase and was not dependent on the stationary-phase sigma factor,
      RpoS. slyA mutant Salmonella strains were sensitive to oxidative products of the
      respiratory burst, including hydrogen peroxide and the products of the redox
      cycling compound paraquat, but not to nitric oxide donors. These results suggest
      that the SlyA regulon is activated during infection of the host and is required
      for resistance to toxic oxidative products of the reticuloendothelial system.

PMID- 9284145
TI  - Role of interleukin 12 in experimental neonatal sepsis caused by group B
      streptococci.
AB  - Cytokines are suspected to play an important role in systemic infections by group
      B streptococci (GBS), an important cause of neonatal sepsis. This work was
      undertaken to determine if interleukin 12 (IL-12) is produced in mouse pups
      infected with GBS and has a role in this sepsis model. IL-12 elevations were
      measured by both an enzyme-linked immunosorbent assay and a bioassay in plasma
      samples obtained from 12 to 72 h after GBS challenge. Pretreatment with
      neutralizing anti-IL-12 antibodies significantly increased lethality and blood
      CFU (P < 0.05). Conversely, either prophylactically or therapeutically
      administered recombinant IL-12 (rIL-12) significantly improved survival time and
      decreased blood CFU. Since these beneficial effects were associated with
      increased spleen gamma interferon (IFN-gamma) production, we examined whether the
      latter cytokine mediated the observed rIL-12 effects. Pretreatment with
      neutralizing anti-IFN-gamma monoclonal antibodies significantly counteracted the
      beneficial effects of rIL-12 on lethality. Our data indicate that rIL-12 is a
      possible candidate for treatment of GBS sepsis and that its activities in this
      model are at least partially mediated by IFN-gamma.

PMID- 9284146
TI  - A proposed role for the lutropin receptor in contact-inducible gonococcal
      invasion of Hec1B cells.
AB  - We previously reported the existence of a contact-inducible, enhanced invasion
      phenotype in the obligate human pathogen Neisseria gonorrhoeae. Our present
      studies showed that the ability of glutaraldehyde-fixed eucaryotic cells to
      convert gonococci (GC) to this invasive phenotype (Inv+) is limited to cells
      derived from reproductive tissues. We present evidence that GC recognize the
      lutropin receptor (LHr), which recognizes both luteinizing hormone and human
      chorionic gonadotropin (hCG), as the tissue-specific environmental signal that
      induces the conversion of GC to the Inv+ phenotype. By competitive binding
      studies, we showed that Inv+ GC bind to Hec1B cells, a human endometrial cell
      line, by a unique adhesin not present on noninduced GC and that this Inv+ GC
      specific binding is completely blocked by the addition of hCG. We demonstrated
      that limiting the access of GC to LHr decreases the ability of the host cell to
      both convert GC to the Inv+ phenotype and serve as a target for Inv+ GC invasion.
      We propose a model of GC invasion of Hec1B cells in which the LHr plays a dual
      role both as an induction signal and as part of the internalization mechanism.
      This utilization of LHr could account for both the preponderance of complicated
      GC disease in women and the observed correlation of the disease with the onset of
      menses.

PMID- 9284148
TI  - Identification of a Streptococcus gordonii SspB domain that mediates adhesion to
      Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis, a primary pathogen in adult periodontitis, may
      establish itself in the oral cavity by adhering to early plaque bacteria such as
      Streptococcus gordonii. Our previous studies (R. J. Lamont et al., Microbiology
      140:867-872, 1994) suggested that this interaction is mediated by the SspB
      polypeptide, a member of the antigen I/II family of streptococcal surface
      proteins. S. gordonii was recently shown to express a second Ssp polypeptide
      (SspA) that resembles SspB and the structurally homologous antigen I/II
      polypeptide (Pac) of Streptococcus mutans. To determine if all of these related
      antigen I/II proteins interacted with P. gingivalis, SspA, SspB, and Pac were
      tested for adhesion to P. gingivalis cells. Both of the S. gordonii Ssp proteins
      bound labeled target cells, whereas the S. mutans Pac polypeptide did not,
      suggesting that antigen I/II-mediated binding of P. gingivalis by streptococci
      may be species specific. To investigate the molecular basis for this functional
      difference, the P. gingivalis binding domain of SspB was mapped. The binding
      properties of a family of truncated SspB polypeptides lacking C-terminal
      sequences were determined. In addition, the lack of binding activity exhibited by
      the Pac protein was exploited to construct and analyze chimeric SspB-Pac
      polypeptides. Both approaches revealed that the region defined by residues 1167
      to 1250 of SspB was essential for P. gingivalis binding. This region of SspA and
      SspB is entirely conserved, consistent with the binding properties determined for
      these proteins. However, the corresponding region of Pac differs in both the
      primary sequence and predicted secondary structure, suggesting that the overall
      structure of this domain may define its functional activity.

PMID- 9284147
TI  - Molecular characterization of murine humoral immune response to botulinum
      neurotoxin type A binding domain as assessed by using phage antibody libraries.
AB  - To produce antibodies capable of neutralizing botulinum neurotoxin type A
      (BoNT/A), the murine humoral immune response to BoNT/A binding domain (H(C)) was
      characterized at the molecular level by using phage antibody libraries. Mice were
      immunized with BoNT/A H(C), the spleens were harvested, and single-chain Fv
      (scFv) phage antibody libraries were constructed from the immunoglobulin heavy
      and light chain variable region genes. Phage expressing BoNT/A binding scFv were
      isolated by selection on immobilized BoNT/A and BoNT/A H(C). Twenty-eight unique
      BoNT/A H(C) binding scFv were identified by enzyme-linked immunosorbent assay and
      DNA sequencing. Epitope mapping using surface plasmon resonance in a BIAcore
      revealed that the 28 scFv bound to only 4 nonoverlapping epitopes with
      equilibrium constants (Kd) ranging from 7.3 x 10(-8) to 1.1 x 10(-9) M. In a
      mouse hemidiaphragm assay, scFv binding epitopes 1 and 2 significantly prolonged
      the time to neuroparalysis, 1.5- and 2.7-fold, respectively, compared to toxin
      control. scFv binding to epitopes 3 and 4 showed no protection against
      neuroparalysis. A combination of scFv binding epitopes 1 and 2 had an additive
      effect on time to neuroparalysis, which increased to 3.9-fold compared to the
      control. The results suggest that there are two "productive" receptor binding
      sites on H(C) which lead to toxin internalization and toxicity. Blockade of these
      two epitopes with monoclonal antibodies may provide effective immunoprophylaxis
      or therapy against BoNT/A intoxication.

PMID- 9284149
TI  - Interaction of Mycobacterium avium with environmental amoebae enhances virulence.
AB  - Environmental mycobacteria are a common cause of human infections. Recently,
      contaminated domestic water supplies have been suggested as a potential
      environmental source of several mycobacterial diseases. Since many of these
      mycobacterial species replicate best intracellularly, environmental hosts have
      been sought. In the present study, we examined the interaction of Mycobacterium
      avium with a potential protozoan host, the water-borne amoeba Acanthamoeba
      castellanii. We found that M. avium enters and replicates in A. castellanii. In
      addition, similar to that shown for mycobacteria within macrophages, M. avium
      inhibits lysosomal fusion and replicates in vacuoles that are tightly juxtaposed
      to the bacterial surfaces within amoebae. In order to determine whether growth of
      M. avium in amoebae plays a role in human infections, we tested the effects of
      this growth condition on virulence. We found that growth of M. avium in amoebae
      enhances both entry and intracellular replication compared to growth of bacteria
      in broth. Furthermore, amoeba-grown M. avium was also more virulent in the beige
      mouse model of infection. These data suggest a role for protozoa present in water
      environments as hosts for pathogenic mycobacteria, particularly M. avium.

PMID- 9284151
TI  - Effect of cytolethal distending toxin on F-actin assembly and cell division in
      Chinese hamster ovary cells.
AB  - Cytolethal distending toxin (CDT) is a newly described toxin produced by a number
      of enteropathogens, including Campylobacter jejuni, various Escherichia coli
      strains, and a few Shigella species. CDT induces distension and eventual death of
      a number of transformed cell lines. Here, we extend previous studies by
      demonstrating that morphological changes in CDT-treated Chinese hamster ovary
      cells are coincident with changes in cytoskeletal structure and an inhibition of
      cell proliferation. CDT-treated cells underwent a progressive accumulation of F
      actin assemblies which microscopically resembled actin stress fibers.
      Accumulation of the stress fiber-like structures in CDT-treated cells was
      accompanied by an apparent blockage of cell division. Multinucleation was
      detected in some cells but did not constitute a significant feature of CDT
      action. Although toxin-treated cells failed to divide, cell viability remained
      high for the first 4 days following toxin treatment, as evidenced by trypan blue
      exclusion and neutral red uptake. [3H]thymidine incorporation studies on CDT
      treated cells were consistent with a blockage of cell proliferation without a
      direct inhibition of DNA synthesis. Although the progression of toxin action
      developed slowly, a 2-min exposure to CDT resulted in an irreversible development
      of toxicity. Together, our data indicate that CDT affects F-actin assembly within
      target cells and may interrupt the regulation or function of cell cycle-dependent
      events leading to cytokinesis.

PMID- 9284150
TI  - Exposure to low oxygen tension and increased osmolarity enhance the ability of
      Mycobacterium avium to enter intestinal epithelial (HT-29) cells.
AB  - Current evidence indicates that Mycobacterium avium infection in patients with
      AIDS is acquired mostly through the gastrointestinal (GI) tract and that M. avium
      binds to and invades GI mucosal cells in vitro. Since M. avium is exposed to
      specific environmental conditions in the GI tract such as changes in pH, low
      oxygen (O2) tension, increased osmolarity, and low concentration of iron, we
      investigated the effects of these conditions on the bacterium's ability to enter
      HT-29 intestinal cells. M. avium 101 (serovar 1) was cultured in 7H9 broth and
      then exposed to pH 4.5 to 8.0, low O2 tension, 0.1 to 0.3 M dextrose, and absence
      of iron for 2 h. After washing, bacteria (10(7)/ml) were used in the invasion
      assay. Confluent HT-29 cells were exposed to 10(6) bacteria for 1 h and then
      treated with amikacin (200 microg/ml) for 2 h to selectively kill extracellular
      but not intracellular M. avium. The supernatant was then removed, the monolayer
      was lysed, and the lysate was plated onto 7H10 agar plates. While exposure to
      acidic and basic pHs, as well as iron-free medium, had no significant effect on
      M. avium invasion of intestinal epithelial cells, low O2 tension and increased
      osmolarity enhanced invasion 11- and 9-fold, respectively, compared with the
      control. Exposure of M. avium to the combination of low O2 concentration and
      hyperosmolarity resulted in an approximate 10- to 15-fold increase in penetration
      of HT-29 cells. Hyperosmolarity and low O2 tension induced the invasive M. avium
      phenotype and can be useful for the identification of genes associated with M.
      avium invasion of intestinal mucosa.

PMID- 9284152
TI  - Increased susceptibility of RAG-2 SCID mice to dissemination of endodontic
      infections.
AB  - Specific immunity has been implicated in the pathogenesis of periapical lesions,
      although the extent to which these mechanisms are actually involved in either
      protection or destruction of the pulp-periapex complex is yet to be established.
      To investigate this question we compared periapical-lesion pathogenesis in RAG-2
      severe combined immunodeficient (SCID) mice with immunocompetent control mice
      following surgical pulp exposure. In order to equalize the bacterial challenge,
      an infection protocol using Prevotella intermedia, Fusobacterium nucleatum,
      Peptostreptococcus micros, and Streptococcus intermedius was devised. The results
      demonstrated that after infection, the proportion of the root canal flora
      represented by the four pathogens was almost identical in both groups (39.9 and
      42.2% for RAG-2 and immunocompetent control mice, respectively). The effects of
      abrogation of T- and B-cell mechanisms on periapical pathogenesis were then
      assessed. Approximately one-third of the RAG-2 mice developed endodontic
      abscesses, while no immunocompetent controls had abscesses, results which
      indicated regional dissemination of the infection. A similar incidence of
      abscesses was found in two additional experiments. Abscessed RAG-2 teeth had
      significantly larger periapical lesions than did nonabscessed RAG-2 teeth (P < or
      = 0.05) and exposed immunocompetent controls (P < or = 0.01), whereas
      nonabscessed RAG-2 teeth were not significantly different from those of exposed
      immunocompetent controls in periapical-lesion size. We conclude that B- and T
      cell-mediated immunity protects the host from the dissemination of endodontic
      infections and that RAG-2 mice are more susceptible to infection-induced pulp
      periapex destruction.

PMID- 9284153
TI  - Peyer's patch adherence of enteropathogenic Escherichia coli strains in rabbits.
AB  - RDEC-1 (serotype O15) is an attaching and effacing strain of rabbit
      enteropathogenic Escherichia coli (REPEC) that causes diarrhea in postweanling
      rabbits. It expresses AF/R1 pili that mediate Peyer's patch M-cell adherence. We
      investigated Peyer's patch adherence, the presence of virulence genes, ileal
      brush border aggregation, and pilus expression in 9 strains representing several
      serotypes of REPEC as well as in two commensal strains. Postweanling rabbits were
      inoculated with 10(6) organisms and sacrificed at 24 h, and tissues were prepared
      for examination by light microscopy. Strains B10 and RDEC-1 were also studied at
      12 and 72 h postinoculation. All REPEC strains were eaeA positive, expressed
      pili, and adhered to ileal brush borders. Both commensal strains expressed pili,
      and one strain adhered to brush borders. All REPEC strains demonstrated some
      degree of Peyer's patch lymphoid follicle adherence, ranging from diffuse
      coverage to small patches covering two to three dome epithelial cells. Strains
      C102 and C110 had genes homologous with the structural subunit gene of the AF/R1
      pilus (afrA) of RDEC-1, which correlated with greater degrees of lymphoid
      follicle adherence and lesser degrees of ileal villus adherence. The observation
      that all REPEC strains adhere to Peyer's patch epithelium suggests the
      possibility that human strains of enteropathogenic E. coli (EPEC) might do
      likewise. EPEC strains might thus serve as mucosal vaccine vectors in humans.
      Better understanding of the molecular mechanism of REPEC adherence should provide
      a model for the targeting of the Peyer's patch in humans.

PMID- 9284154
TI  - Heterogeneity of antibodies reactive with the dominant antigen of Actinobacillus
      actinomycetemcomitans.
AB  - The serotype b-specific carbohydrate antigen (SbAg) of Actinobacillus
      actinomycetemcomitans Y4 is reported to be the O antigen of lipopolysaccharide,
      and the highest titers of serum antibody reactive with A. actinomycetemcomitans
      in early-onset periodontitis (EOP) patients bind SbAg. These high titers of serum
      antibody reactive with SbAg are associated with a lesser extent and severity of
      periodontal disease. The aim of this study was to determine if a limited number
      of genes code for anti-SbAg antibodies as has been shown for immunoglobulin G
      (IgG) reactive with the type b polysaccharide from Haemophilus influenzae. Serum
      IgG reactive with the SbAg was prepared from 20 high-titer EOP patients by
      affinity chromatography. The IgG subclass concentrations were determined, and
      heterogeneity was analyzed by isoelectric focusing (IEF). IgG2 was the dominant
      subclass (83% of total IgG) in the anti-SbAg IgG fraction and represented an
      average of 1.33% of total serum IgG2. The IgG2 reactive with SbAg was isolated
      from the affinity-purified IgG fraction by affinity chromatography with protein A
      and subclass-specific monoclonal antibodies. On IEF gels, only 4 to 20 bands were
      observed in the anti-SbAg IgG fractions, indicating limited heterogeneity. N
      terminal amino acid sequence analysis of eight representative anti-SbAg IgG2
      preparations indicated that variable heavy and light chains consisted largely of
      V(H)III and V(kappa)II, respectively. However, a significant fraction of anti
      SbAg may use V(H) and V(lambda) genes with blocked N termini. In short, these
      findings indicate that IgG reactive with SbAg is very much like the antibody
      reactive with H. influenzae type b polysaccharide. Similarities include IgG2
      dominance, limited bands on IEF gels, supporting an oligoclonal response, and use
      of genes from V(H)III and V(kappa)II regions.

PMID- 9284155
TI  - Shiga toxin-producing Escherichia coli isolates from cases of human disease show
      enhanced adherence to intestinal epithelial (Henle 407) cells.
AB  - Shiga toxin-producing Escherichia coli (STEC) strains are a diverse group of
      organisms which are known to cause diarrhea and hemorrhagic colitis in humans. We
      have recently described a large food-borne outbreak of STEC disease caused by
      contaminated semidry fermented sausage (A. W. Paton, R. Ratcliff, R. M. Doyle, J.
      Seymour-Murray, D. Davos, J. A. Lanser, and J. C. Paton, J. Clin. Microbiol.
      34:1622-1627, 1996). STEC strains belonging to several O serotypes were isolated
      from the contaminated food source, but of these, only a subset were isolated from
      patients with diarrhea or hemolytic-uremic syndrome (HUS). In the present study,
      we characterized these STEC isolates with respect to the presence of putative
      virulence-associated genes and the capacity to adhere to a human intestinal
      epithelial cell line (Henle 407). The O111:H- STEC strain 95NR1 (isolated from
      one of the outbreak HUS patients) was shown to adhere to Henle 407 cells in a
      dose-dependent, mannose-resistant fashion. Microscopic examination revealed a
      diffuse pattern of adherence for this as well as several other STEC strains.
      Interestingly, the adherence of STEC strains from HUS cases (both outbreak
      related and sporadic) was significantly greater than that of STEC strains found
      in the contaminated food source but not found in any patients. These studies
      support the hypothesis that an enhanced capacity to adhere to intestinal cells is
      one of the factors which distinguishes human-virulent STEC strains from those of
      lesser clinical significance.

PMID- 9284156
TI  - The trypanocidal Cape buffalo serum protein is xanthine oxidase.
AB  - Plasma and serum from Cape buffalo (Syncerus caffer) kill bloodstream stages of
      all species of African trypanosomes in vitro. The trypanocidal serum component
      was isolated by sequential chromatography on hydroxylapatite, protein A-G, Mono
      Q, and Superose 12. The purified trypanocidal protein had a molecular mass of 150
      kDa, and activity correlated with the presence of a 146-kDa polypeptide detected
      upon reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Amino
      acid sequences of three peptide fragments of the 146-kDa reduced polypeptide,
      ligand affinity and immunoaffinity chromatography of the native protein, and
      sensitivity to pharmacological inhibitors, identified the trypanocidal material
      as xanthine oxidase (EC 1.1.3.22). Trypanocidal activity resulted in the
      inhibition of trypanosome glycolysis and was due to H2O2 produced during
      catabolism of extracellular xanthine and hypoxanthine by the purine catabolic
      enzyme.

PMID- 9284157
TI  - Streptococcus sanguis expresses a 150-kilodalton two-domain adhesin:
      characterization of several independent adhesin epitopes.
AB  - Streptococcus sanguis binds to saliva-coated hydroxylapatite (sHA), an in vitro
      model of the enamel pellicle. To learn if more than one adhesin functions during
      adhesion, 12 reactive monoclonal antibodies (MAbs) were isolated by screening
      against both adhesive and nonadhesive strains. Two of these MAbs, 1.1 and 1.2,
      inhibited adhesion in a dose-dependent fashion, although maximum inhibition with
      either was only 37%. When these two MAbs plus a polyclonal antibody to P1-like
      adhesin were combined, the inhibition was additive to about 82%. These data
      indicated that there were at least three distinct, functional adhesion epitopes
      on the surface of S. sanguis. Western blot analyses of S. sanguis surface
      macromolecules showed antigens at 36 and 56 (with MAb 1.2), 87 and 150 (with both
      MAb 1.1 and MAb 1.2), and 100, 130, and 170 kDa (with anti-P1 antibody). The
      antigens were eluted from gels. Isolated antigens and corresponding antibodies
      inhibited adhesion similarly. Additivity experiments suggested the distinct
      epitopes were in three groups: (i) 36/56 kDa, (ii) 87/150 kDa, and (iii)
      100/130/170 kDa. The 150-kDa antigen reacting with both MAbs was isolated from
      gels and digested with trypsin. The digestion revealed a series of tryptic bands.
      A band at 38 kDa reacted with MAb 1.1 whereas a band at 54 kDa reacted with MAb
      1.2 in Western blot analysis, indicating two distinct adhesive epitopes on the
      150-kDa antigen. These data strongly suggest that S. sanguis adhesion to sHA is
      maximized when several adhesin epitopes are coexpressed on surface antigens of
      different sizes.

PMID- 9284159
TI  - Streptococcal mitogenic exotoxin Z, a novel acidic superantigenic toxin produced
      by a T1 strain of Streptococcus pyogenes.
AB  - Streptococcus pyogenes T1 was previously found to produce an acidic mitogenic
      exotoxin, designated A beta, antigenically distinct from erythrogenic toxin type
      A (ETA) of strains T1 and NY5. Following chemical analysis and biological
      characterization, we have renamed this toxin streptococcal mitogenic exotoxin Z
      (SMEZ). Physicochemical separation of SMEZ from ETA was successfully performed on
      a hydrophobic chromatograph. The isoelectric point was pH 5.3, and the molecular
      size was estimated to be 28 kDa. These values were similar to those of ETA, but
      the amino acid composition and the NH2-terminal sequence of SMEZ were distinct
      from those of any mitogenic exotoxins hitherto described. Its mitogenic activity
      was found to be more potent than that of ETA in rabbit lymphocyte cultures. A
      specific antiserum raised against SMEZ did not cross-react with ETA, ETB, or ETC
      in the neutralization tests of mitogenic and erythrogenic activities. Its
      superantigenic nature was evident from the reverse transcriptase PCR findings of
      the T-cell receptor Vbeta profiles of rabbit lymphocytes stimulated in vitro. The
      Vbeta 8 subfamily was unique to SMEZ, while the Vbeta 2 and 6 subfamilies were
      found to be common among lymphocytes stimulated with ETA, ETB, ETC, or SMEZ. The
      results from this study provide an additional example of the diversity that
      exists among mitogenic or superantigenic exotoxins of streptococcal origin.

PMID- 9284158
TI  - Mannan-specific immunoglobulin G antibodies in normal human serum mediate
      classical pathway initiation of C3 binding to Candida albicans.
AB  - Candida albicans activates both the classical and alternative complement
      pathways. Previous studies found that immunoglobulin G (IgG) in normal human
      serum (NHS) mediates classical pathway initiation. The goal of this study was to
      determine the role of candidal mannan-specific human IgG antibodies in complement
      activation. Mannan was purified from the yeast cells, and naturally occurring
      antimannan IgG was isolated from pooled NHS or plasma samples by immunoaffinity
      chromatography. Early activation and binding of C3, characteristics of classical
      pathway activity, were abolished in yeast- or mannan-absorbed serum but could be
      restored to absorbed serum with added purified antimannan IgG in a dose-dependent
      manner. Microscopically, the immunofluorescence pattern of initial C3 binding was
      diffuse over the entire cell surface for yeast cells incubated in NHS or in
      mannan-absorbed NHS supplemented with antimannan IgG but was asynchronous and
      focal for yeast cells incubated in EGTA-treated or mannan-absorbed NHS. The
      antimannan IgG level in serum samples from 21 donors varied from 17 to 570
      microg/ml of serum compared to 220 microg in pooled NHS samples. The rate of
      initial C3 binding to yeast cells correlated with the level of antimannan IgG in
      sera from different individuals (r2 = 0.94) and could be accelerated in sera
      containing lower amounts of antimannan IgG with exogenous antimannan IgG. These
      observations identify antimannan IgG as the initiator of classical pathway C3
      deposition on C. albicans. Given the variability in the levels of antimannan
      antibodies in sera from different individuals, the presence or absence of these
      antibodies may be an important determinant of host resistance to disseminated
      candidiasis.

PMID- 9284160
TI  - Leukocytes in a Plasmodium falciparum-infected blood meal reduce transmission of
      malaria to Anopheles mosquitoes.
AB  - Mosquitoes are infected with Plasmodium falciparum by taking a blood meal from a
      gametocyte carrier. Since a mosquito takes a volume of 1 to 2 microl, a blood
      meal may contain 1 x 10(4) to 3 x 10(4) leukocytes (WBC). The majority of WBC are
      composed of neutrophils which may phagocytose and kill developing gametes inside
      the mosquito midgut. Phagocytosis was measured in vitro by a luminol-dependent
      chemiluminescence (CL) assay. In the presence of P. falciparum gametes, sera from
      areas of endemicity had an increased CL response compared to controls. In
      mosquito membrane feeding experiments some such sera showed a transmission
      reduction which was related to the presence of viable WBC. The results of this
      study suggest that phagocytosis of opsonized gametes inside the mosquito midgut
      occurs and can contribute to a reduction in the transmission of P. falciparum
      parasites.

PMID- 9284161
TI  - Mucoid Pseudomonas aeruginosa in cystic fibrosis: characterization of muc
      mutations in clinical isolates and analysis of clearance in a mouse model of
      respiratory infection.
AB  - A distinguishing feature of Pseudomonas aeruginosa isolates from cystic fibrosis
      (CF) patients is their mucoid, exopolysaccharide alginate-overproducing
      phenotype. One mechanism of conversion to mucoidy is based on mutations in the
      algU mucABCD cluster, encoding the stress sigma factor AlgU and its regulators.
      However, conversion to mucoidy in laboratory strains can be achieved via
      mutations in other chromosomal sites. Here, we investigated mechanisms of the
      emergence of mucoid P. aeruginosa in CF by analyzing the status of mucA in a
      collection of mucoid P. aeruginosa isolates from 53 CF patients. This negative
      regulator of algU, when inactivated under laboratory conditions, causes
      conversion to mucoidy. The overall frequency of mucA alterations in mucoid CF
      isolates was 84%. Nucleotide sequence analyses revealed that the majority of the
      alterations caused premature termination of the mucA coding sequence. Comparison
      of paired nonmucoid and mucoid P. aeruginosa isolates from three CF patients
      indicated the presence of mucA mutations only in the mucoid strains.
      Interestingly, mucoid P. aeruginosa isolates from urinary tract infections also
      had mutations in the mucA gene. Clearance of CF isolates from the murine lung was
      investigated in an aerosol infection model with C57BL/6J, BALB/c, and DBA/2NHsd
      mice. Two CF strains, selected for further study based on the dependence of their
      alginate production on the concentration of salt in the medium, were used to
      examine the effects of mucoidy on pulmonary clearance. Statistically significant
      improvement in recovery from the murine lung of viable mucoid P. aeruginosa cells
      relative to the nonmucoid bacteria was observed in the majority of mouse strains
      tested. Collectively, the results reported here suggest that mucA is most likely
      the preferential site for conversion to mucoidy in CF and that alginate
      overproduction in mucA-mutant P. aeruginosa improves its resistance to the innate
      clearance mechanisms in the lung.

PMID- 9284162
TI  - Elevated levels of macrophage inflammatory protein 2 in severe murine peritonitis
      increase neutrophil recruitment and mortality.
AB  - We hypothesized that chemokines may play important roles in a cecal ligation and
      puncture (CLP) model of septic peritonitis in CD-1 mice. Concentrations of C-X-C
      (macrophage inflammatory protein 2 [MIP-2] and ENA-78) and C-C (MIP-1alpha and
      JE) chemokines were measured (by enzyme-linked immunosorbent assay) in serum,
      peritoneal lavage fluid, lung, and liver at 4, 8, 24, 48, and 96 h after CLP.
      Significant elevations in all measured chemokines occurred in peritoneal fluid
      after CLP (P < 0.05). MIP-2, in particular, increased dramatically (>400-fold, P
      < 0.001) in peritoneal fluid, serum, and to a lesser extent lung and liver (P <
      0.05). Increased MIP-2 was correlated with severity of sepsis (P < 0.001). To
      determine the significance of this finding, mice were passively immunized prior
      to CLP with polyclonal antibody to MIP-2, which decreased mortality from 85 to
      38% at 96 h (P < 0.01). To further understand the mechanism of the effect of MIP
      2, additional measurements demonstrated that anti-MIP-2 prior to CLP decreased
      the percent neutrophils in peritoneal fluid (55% +/- 12%, compared with 82% +/-
      10% in controls), but no significant changes in tumor necrosis factor alpha,
      interleukin-6, or interleukin-10 occurred. MIP-2 contributes to the inflammatory
      response and overall mortality in this model of severe septic peritonitis,
      possibly by increasing recruitment of neutrophils, which clear bacteria but may
      also injure the host.

PMID- 9284163
TI  - Evaluation of a bivalent (CVD 103-HgR/CVD 111) live oral cholera vaccine in adult
      volunteers from the United States and Peru.
AB  - To provide optimum protection against classical and El Tor biotypes of Vibrio
      cholerae O1, a single-dose, oral cholera vaccine was developed by combining two
      live, attenuated vaccine strains, CVD 103-HgR (classical, Inaba) and CVD 111 (El
      Tor, Ogawa). The vaccines were formulated in a double-chamber sachet; one chamber
      contained lyophilized bacteria, and the other contained buffer. In the first
      study, 23 U.S. adult volunteers received CVD 103-HgR at 10(8) CFU plus CVD 111 at
      10(8), 10(7), or 10(6) CFU, CVD 111 alone at 10(7) CFU, or placebo. In the second
      study, 275 Peruvian adults were randomized to receive CVD 103-HgR at 10(9) CFU
      plus CVD 111 at 10(9) or 10(8) CFU, CVD 111 alone at 10(9) CFU, CVD 103-HgR alone
      at 10(9) CFU, or placebo. Three of 15 U.S. volunteers who received CVD 111 at
      10(7) or 10(8) CFU developed mild diarrhea, compared to none of 4 who received
      CVD 111 at 10(6) CFU and 1 of 4 who received placebo. Twelve (63%) of 19 vaccine
      recipients shed the El Tor vaccine strain. All but one volunteer developed
      significant Ogawa and Inaba vibriocidal antibody titers. Volunteers who received
      CVD 111 at 10(7) CFU had geometric mean Ogawa titers four to five times higher
      than those of volunteers who received the lower dose. In the second study, all
      dosage regimens were well tolerated in Peruvians. About 20% of volunteers who
      received CVD 111 at the high dose excreted the El Tor organism, compared to 7% in
      the low-dose group. CVD 111 was detected in the stools of two placebo recipients,
      neither of whom had symptoms or seroconverted. In all vaccine groups, 69 to 76%
      developed fourfold rises in Inaba vibriocidal antibodies. Among those who
      received the bivalent vaccine, 53 to 75% also developed significant rises in
      Ogawa vibriocidal antibodies. We conclude that it is feasible to produce a single
      dose, oral bivalent vaccine that is safe and immunogenic against both biotypes
      (El Tor and classical) and both serotypes (Inaba and Ogawa) of cholera for
      populations in both developed and developing parts of the world.

PMID- 9284164
TI  - Binding of vitronectin to opa-expressing Neisseria gonorrhoeae mediates invasion
      of HeLa cells.
AB  - Neisseria gonorrhoeae induces local infections in the human genitourinary tract
      and can disseminate to other organs to cause severe disease. Blood-derived
      factors present in the genital mucosa have been suggested to facilitate the
      spread of N. gonorrhoeae in disseminated gonococcal infections. Using gentamicin
      invasion assays and confocal microscopy, we observed a strong stimulatory effect
      of fetal calf serum (FCS) on the gonococcal invasion of HeLa cells. FCS-mediated
      invasion was dependent on the expression of the epithelial cell invasion
      associated Opa protein (plasmid-encoded Opa50 or its chromosomal homolog Opa30),
      while N. gonorrhoeae expressing noninvasive Opa proteins (Opa(51-60)) or no Opa
      protein (Opa-) was not invasive even in the presence of FCS. Incubation of N.
      gonorrhoeae MS11 with biotinylated FCS revealed a 78-kDa protein as the prominent
      protein binding to Opa50- or Opa30-expressing gonococci. This protein was
      recognized by antibodies against vitronectin (VN) in Western blots. Purified
      human or bovine VN efficiently bound to Opa50-expressing gonococci, while binding
      to noninvasive Opa- or Opa52-expressing gonococci was significantly lower.
      Binding of VN was inhibited by heparin in a concentration-dependent manner,
      indicating that the heparin binding sites present in VN or Opa50 may play an
      essential role in this interaction. Based on gentamicin invasion assays and
      confocal microscopy studies, VN binding was associated with an increased invasion
      of Opa50- and Opa30-expressing gonococci into HeLa cells. The ability of VN to
      mediate entry into epithelial cells may constitute an important event in the
      pathogenesis of local as well as disseminated gonococcal infections.

PMID- 9284165
TI  - Expression of a Schistosoma mansoni 28-kilodalton glutathione S-transferase in
      the livers of transgenic mice and its effect on parasite infection.
AB  - Schistosomiasis is a debilitating tropical disease for which an effective vaccine
      is needed. A 28-kDa glutathione S-transferase from Schistosoma mansoni (Sm28GST)
      has been shown to induce protective immunity. Sm28GST possesses significant
      sequence identity to mammalian GST isoforms. In order to study self-reactivity in
      mice immunized with Sm28GST and the concomitant phenomena of immune tolerance and
      epitope suppression, as well as their consequences for the protective immunity
      induced by this vaccination, we developed transgenic (Tg) mice that express
      Sm28GST under the control of a part of the mouse transferrin gene promoter. A
      study of (P28)Tg mice showed that the expression of Sm28GST was strictly
      localized in pericentrolobular hepatocytes. No histological change, inflammatory
      infiltrates, or modification of seric L-aspartate: 2-oxoglutarate
      aminotransferase concentration was observed over an 18-month period, despite a
      cross-reactivity between Sm28GST and a mouse molecule of 30 kDa. The
      immunoglobulin G anti-Sm28GST response of (P28)Tg mice immunized with recombinant
      Sm28GST was lower (P < 0.001) than that observed in non-(P28)Tg littermates and
      inversely proportional of Sm28GST liver expression. The response of non-(P28)Tg
      mouse spleen cells to Sm28GST stimulation was greater (P < 0.01) than that
      observed with (P28)Tg mouse spleen cells. (P28)Tg mice infected with 40 S.
      mansoni furcocercariae harbored more worms (P < 0.05) than did non-(P28)Tg
      control mice. The increase in the level of infection in (P28)Tg mice was
      reflected in concomitant increases in the numbers of adult worms and schistosome
      eggs found in livers and intestines after whole-body perfusion at 56 days
      postinfection, but no relative increase in the fertility of individual female
      worms was observed. The results obtained argue for the involvement of Sm28GST in
      reducing levels of infection and support the view that this enzyme has a central
      role in the maintenance of parasite viability, at least during its migration
      through host tissues.

PMID- 9284166
TI  - Fimbriae and the hemagglutinating adhesin HA-Ag2 mediate adhesion of
      Porphyromonas gingivalis to epithelial cells.
AB  - The mechanisms by which Porphyromonas gingivalis, a gram-negative anaerobic
      bacterium, is pathogenic for the periodontium remain largely hypothetical.
      Invasion of host tissues by P. gingivalis is believed to require adhesion of the
      bacterium to host cells. The aim of this study was to use monoclonal antibodies
      (MAbs) to characterize the bacterial cell surface component(s) acting as a ligand
      binding to a receptor on epithelial cells. Surface antigens of P. gingivalis ATCC
      33277 were obtained as a glass bead-EDTA extract (GBE), and antiserum against the
      GBE was produced in rabbits. Epithelial cell membrane proteins (ECMP) were
      prepared from a homogenate of the SK-MES-1 cell line with Triton X-100. The
      antigen/ligand profile of GBE was resolved by crossed immunoaffinity
      electrophoresis by using ECMP in the first-dimension gel. The migration of one
      immunoprecipitate (IP) was retarded, indicating a ligand-receptor interaction
      between a surface antigen of P. gingivalis and a complementary binding site on
      the epithelial cell membrane. The corresponding IP in the GBE/anti-GBE
      immunoelectrophoresis profile was excised from replicate gels to immunize mice
      for production of MAbs specific for the bacterial ligand. Five MAbs were obtained
      and tested for reactivity with GBE in immunoblots and for inhibition of the
      interaction between GBE and ECMP. Immunoblots revealed polypeptides at 28, 42,
      43, and 49 kDa. Inhibition tests were positive for all five MAbs. These results
      are conclusive evidence that the MAbs recognize functional epitopes involved in
      the adherence of P. gingivalis to epithelial cells and that the adhesins are
      likely associated with fimbriae and the hemagglutinating adhesin HA-Ag2.

PMID- 9284167
TI  - Inhibition of nitric oxide interrupts the accumulation of CD8+ T cells
      surrounding Plasmodium berghei-infected hepatocytes.
AB  - The elimination of liver-stage malaria parasites by nitric oxide (NO)-producing
      hepatocytes is regulated by T cells. Both CD8+ and CD4+ T cells, which surround
      infected hepatocytes, are evident by 24 h after sporozoite challenge in Brown
      Norway rats previously immunized with irradiated Plasmodium berghei sporozoites.
      While the number of CD4+ T cells remained the same beyond 24 h postchallenge, the
      number of CD8+ T cells increased three- and sixfold by 31 and 44 h, respectively.
      This increase in the number of CD8+ T cells correlated with a decrease in the
      number of intrahepatic parasites. In immunized rats, intrahepatic parasites were
      reduced in number by 31 h after sporozoite challenge and cleared from the liver
      by 44 h, as visualized by P. berghei-specific DNA in situ hybridization. If
      immunized rats were treated with aminoguanidine, a substrate inhibitor of NO
      synthase, at the time of challenge, liver-stage protection was blocked, as shown
      by the increase in parasite liver burden. Further histological examination of
      infected livers from immunized animals treated with aminoguanidine revealed fewer
      and smaller cellular infiltrates surrounding the infected hepatocytes, and the
      number of CD8+ T cells that normally accumulate within the infiltrates was
      drastically reduced. Consequently, the infected hepatocytes were not cleared from
      the liver. We hypothesize that the early production of NO may promote the influx
      and/or enhance local proliferation of malaria parasite-specific CD8+ T cells or a
      CD8+ T-cell subset which is required for parasite clearance.

PMID- 9284168
TI  - Correlation of histopathologic and bacteriologic changes with cytokine expression
      in an experimental murine model of bacteremic Staphylococcus aureus infection.
AB  - Staphylococcus aureus infections are often life threatening. Relatively little is
      known about the host response to these infections, in particular, the role played
      by cytokines. We established a mouse model of bacteremic S. aureus infection to
      correlate bacteriologic findings and pathologic changes with cytokine gene
      expression. Bacterial density in blood and tissue was highest at 1 h and minimal
      by 48 h. Despite the rapid clearance of bacteria, pathologic abnormalities and
      inflammatory cytokines were detected after clearance of the bacteria. The number
      of infiltrating inflammatory cells, as well as the size of inflammatory foci,
      increased with time. Interstitial accumulation of inflammatory cells and tissue
      damage, such as microabscesses, edema, and necrosis progressed following
      clearance of bacteria from the tissues. Levels of tumor necrosis factor and
      interleukin-1 protein in serum were detectable at 1 h and peaked at 4 h.
      Interleukin-6 protein expression showed different kinetics, with low levels
      detected at 1 h and increasing levels at 72 h postinfection. Tumor necrosis
      factor and the interleukins were expressed in inflammatory and noninflammatory
      cells in lung, liver, and heart tissues. Leukocytes in the infected tissues were
      highly reactive with antibodies to the three cytokines, suggesting that activated
      leukocytes are a major source of inflammatory cytokines after staphylococcal
      infection. Expression of interleukin-1 and interleukin-6 in tissue-specific cells
      and endothelial cells was also detected in infected tissues, indicating that
      cells other than leukocytes contribute to the elevated cytokine levels in this
      model. Once initiated, expression of inflammatory cytokines contributes to the
      pathogenesis of S. aureus disease.

PMID- 9284169
TI  - Identification of phosphatidylinositol mannoside as a mycobacterial adhesin
      mediating both direct and opsonic binding to nonphagocytic mammalian cells.
AB  - The molecular basis for the binding of Mycobacterium tuberculosis to
      nonphagocytic cells, which are readily infected in vitro, and the in vivo
      significance of this interaction are incompletely understood. Of six cell types
      tested, we found that only two, Chinese hamster ovary (CHO) fibroblasts and
      primary porcine aortic endothelial cells, were able to bind M. tuberculosis H37Rv
      efficiently in vitro. Binding to both CHO and endothelial cells was markedly
      (three- to fivefold) enhanced by 10 to 20% human or bovine serum, suggesting that
      the bacteria were coated by a serum opsonin. Preincubation with individual
      candidate opsonins revealed that recombinant human mannose-binding protein
      (rMBP), fibronectin, and transferrin were each able to enhance binding threefold.
      Preincubation of bacteria in serum depleted of mannan-binding lectins or in
      genetic MBP-deficient serum resulted in enhancements that were only approximately
      60 and 58%, respectively, of that produced by preincubation in control serum. In
      contrast, serum depleted of fibronectin or transferrin retained its opsonizing
      capacity, suggesting that the latter two are not significant opsonins in whole
      serum. Binding of M. tuberculosis and Mycobacterium smegmatis to both CHO and
      endothelial cells in the presence or absence of serum was blocked (60 to 70%) by
      a monoclonal antibody, MAb 1D1, selected for recognition of intact bacilli. The
      1D1 antigen was purified from mycobacterial cell walls and chemically identified
      as a polar phosphatidylinositol mannoside (PIM). Latex beads coated with purified
      1D1 antigen bound to CHO cells, which was enhanced threefold by serum and
      abolished by periodate treatment, suggesting a requirement for the PIM mannoses
      in opsonic adhesion. This was likely mediated, at least in part, by serum MBP, as
      rMBP bound strongly to 1D1 antigen in both thin-layer chromatography overlay and
      plate binding assays, the latter in a mannan-inhibitable manner. This is the
      first demonstration that mycobacterial PIMs can function as adhesins for binding
      to nonphagocytic cells, both directly and after opsonization with serum proteins,
      including MBP.

PMID- 9284170
TI  - Circulating promyelocytes and low levels of CD16 expression on polymorphonuclear
      leukocytes accompany early-onset periodontitis.
AB  - Early-onset periodontitis (EOP) is characterized by rapidly progressive alveolar
      bone loss, chemotactic defects of neutrophils, and significant familial
      aggregation. We found immature myeloid lineage cells, defined as promyelocytes,
      in the peripheral blood in patients with EOP. A hematological examination of
      peripheral blood cells showed normal reference values regarding cell proportions.
      Flow cytometry revealed significantly lower expression of CD16, a
      glycosylphosphatidylinositol (GPI)-anchored protein, on peripheral neutrophils in
      patients compared with those in age- and sex-matched healthy controls, whereas
      the levels of CD11a and CD11b expression were similar. The chemotactic response
      of neutrophils was lower toward not only formyl-methionyl-leucyl-phenylalanine
      but also complement fragment C5a than that of healthy controls. The expression of
      another GPI-anchored protein, CD14, was equally expressed by controls and
      patients. Therefore, the low level of CD16 expression was not due to the
      incomplete synthesis of the GPI anchor. GPI anchors of CD16 on neutrophils from
      controls and patients were both partially resistant to phosphatidylinositol
      specific phospholipase C. The presence of promyelocytes in peripheral blood, low
      expression of CD16, and low chemotactic response of neutrophils suggest that
      patients with EOP have an abnormal maturation system in myeloid lineage cells in
      the bone marrow, which may be associated with the onset and course of EOP.

PMID- 9284172
TI  - An Edwardsiella tarda strain containing a mutation in a gene with homology to
      shlB and hpmB is defective for entry into epithelial cells in culture.
AB  - Edwardsiella tarda is an enteric pathogen that causes diarrhea, wound infections,
      and death due to septicemia. This species is capable of invading human epithelial
      cell lines, and we have now been able to follow the entry and replication of E.
      tarda within tissue culture host cells. E. tarda escapes from the endocytic
      vacuole within minutes of entry and then replicates within the cytoplasm. Unlike
      other well-studied bacteria that replicate and reside in the cytoplasm, we never
      observed this organism moving directly from cell to cell; instead the bacteria
      spread by lysing the plasma membrane after several rounds of replication. Efforts
      to study the interactions of E. tarda with tissue culture cells are complicated
      by the presence of a potent cytotoxin that the bacterium produces. Using
      transposon mutagenesis, we isolated a noncytotoxic strain of E. tarda. This
      mutant is also defective for hemolysin production. The dual phenotype of this
      strain is consistent with the hypothesis that cytotoxicity is due to the
      previously characterized E. tarda hemolysin activity. The nonhemolytic strain is
      also unable to enter HEp-2 cells. The disrupted gene has sequence similarity to
      members of a family of genes required for transport and activation of the
      hemolysin genes, shlA and hpmA. A cosmid bearing 40 kb of E. tarda DNA, including
      wild-type copies of the E. tarda homologs of the transporter-activator protein
      and the hemolysin itself, confers hemolytic, cytotoxic, and invasive abilities
      upon normally nonhemolytic, noncytotoxic, and noninvasive strains of Escherichia
      coli. Sequence data indicate that the genes required for hemolytic activity are
      linked to a transposable element, suggesting that they arose in the E. tarda
      genome by horizontal transfer.

PMID- 9284171
TI  - Molecular analysis of human cardiac myosin-cross-reactive B- and T-cell epitopes
      of the group A streptococcal M5 protein.
AB  - The group A streptococcal M protein is an important virulence determinant
      eliciting protective and autoimmune responses against the streptococcus and
      cardiac myosin, respectively. In this report, the major human cardiac myosin
      cross-reactive T-cell epitopes of M5 protein are identified and localized to
      myosin-like repeats within the M5 molecule. BALB/c mice were immunized with human
      cardiac myosin, and the dominant myosin-cross-reactive T-cell epitopes of M5
      protein were identified with a panel of 23 overlapping peptides spanning the A,
      B, and C repeat regions of M5 protein. Human cardiac myosin-cross-reactive T-cell
      epitopes of M5 protein were localized to several sequences in the M5 peptides NT4
      (GLKTENEGLKTENEGLKTE), NT5 (KKEHEAENDKLKQQRDTL), B1B2 (VKDKIAKEQENKETIGTL), B2
      (TIGTLKKILDETVKDKIA), B3A (IGTLKKILDETVKDKLAK), and C3 (KGLRRDLDASREAKKQ). The
      NT4 repeated sequence LKTEN was highly homologous with a site conserved in
      cardiac myosins, the B repeat region peptides were 47% homologous to human
      cardiac myosin amino acid sequence, and the C3 sequence RRDL was identical to a
      highly conserved site in skeletal and cardiac myosins. Immunization of BALB/c
      mice with each of the overlapping M5 peptides revealed myosin-cross-reactive B
      cell epitopes throughout the A and C repeat regions and one major epitope in the
      B repeat region containing the previously reported Gln-Lys-Ser-Lys-Gln (QKSKQ)
      epitope. The data suggest that the M5 peptides elicited higher antibody titers to
      cardiac myosin than to skeletal myosin and that several sites in the A and B
      repeat regions of M5 protein induced myocardial inflammatory infiltrates.

PMID- 9284174
TI  - Allelic variation in Streptococcus pneumoniae autolysin (N-acetyl muramoyl-L
      alanine amidase).
AB  - The lytA gene encoding the autolysin of Streptococcus pneumoniae may be a
      virulence determinant. Single-strand conformational polymorphism analysis
      demonstrated heterogenicity throughout the gene in clinical isolates and strains
      from the clonal serotypes 7 and 14. Sequence analysis of part of the choline
      binding domain showed that in two isolates four amino acid substitutions
      occurred.

PMID- 9284173
TI  - In vitro inhibition of Cryptosporidium parvum infection by human monoclonal
      antibodies.
AB  - Cryptosporidium parvum infection of the small epithelial intestine causes
      unremitting diarrhea and malabsorption that can lead to chronic and sometimes
      fatal illness in patients with AIDS. The illness may be ameliorated by passive
      oral immunoglobulin therapy. The objective of this study was to produce anti
      Cryptosporidium human monoclonal antibodies for evaluation as potential therapy.
      All human monoclonal cell lines that produced C. parvum antibodies were
      originally generated from the peripheral blood lymphocytes of a human
      immunodeficiency virus-seronegative woman. She had recovered from C. parvum
      infection and had a high specific antibody titer. Hybridization of these
      lymphocytes with a tumor cell line was accomplished by hypo-osmolar
      electrofusion. Twelve clones were identified by enzyme-linked immunosorbent assay
      (ELISA) as secreting anti-Cryptosporidium antibodies after the initial
      hybridization. From the 12 positive clones, two high antibody-secreting clones,
      17A and 17B, were maintained in long-term culture. A second hybridization
      produced two other human monoclonal cell lines, EC5 and BB2. Human monoclonal
      antibody from the first two cell lines bound to C. parvum sporozoites and oocysts
      by immunofluorescence. The ability of human monoclonal antibodies to inhibit C.
      parvum infection in vitro was assessed by using a human enterocyte cell line,
      HT29.74. The antibodies of the four different human hybridomas inhibited
      infection by 35 to 68% (P < 0.05) compared to a control irrelevant human
      monoclonal antibody derived in a similar fashion. Human monoclonal antibodies are
      candidate molecules for immunotherapy of C. parvum infection.

PMID- 9284175
TI  - Use of cellular depletion analysis to examine circulation of immune effector
      function between the vagina and the periphery.
AB  - Results from an animal model of vaginal candidiasis suggest that Candida-specific
      cell-mediated immunity in the systemic circulation does not mediate protection
      against vaginitis. The present study used cellular depletion analysis to examine
      the circulation of immune effector function between the vagina and the periphery.
      Results showed that anti-Thy-1.2 antibodies given intravenously to mice depleted
      Thy-1+ T lymphocytes in the systemic compartment but not in the vaginal mucosa,
      while the same antibodies injected intravaginally significantly reduced Thy-1+ T
      cells in both the vaginal and systemic compartments. These results support a lack
      or low level of circulation of immune effector function from the periphery to the
      vaginal mucosa.

PMID- 9284176
TI  - Giardia lamblia infections in B-cell-deficient transgenic mice.
AB  - In the present study, we infected B-cell (and antibody-)-deficient transgenic
      mice with the Giardia lamblia clone GS/M-83-H7. These animals were inhibited in
      intestinal anti-Giardia immunoglobulin A (IgA) production and could not resolve
      the parasite infection, and antigenic diversification within the respective
      parasite populations occurred in an unusually slow manner. These findings
      indicate an important immunological function of local IgA antibodies which
      promotes antigenic variation of the parasite and is involved in control of the
      parasite infection.

PMID- 9284177
TI  - Activation of CD8 T cells with specificity for mycobacterial heat shock protein
      60 in Mycobacterium bovis bacillus Calmette-Guerin-vaccinated mice.
AB  - Heat shock protein 60 (hsp60)-specific CD8 T cells lysed Mycobacterium bovis BCG
      infected macrophages in vitro and adoptively transferred protection against
      mycobacterial infection. Moreover, CD8 T cells with this hsp60 specificity were
      activated in vivo by BCG vaccination. Our studies suggest there is participation
      of hsp60-specific CD8 T cells in BCG-induced immunity.

PMID- 9284179
TI  - Failure to detect binding of LcrH to the V antigen of Yersinia pestis.
AB  - V antigen of Yersinia pestis has been reported to bind the chaperone LcrH. We
      were unable to demonstrate this interaction. Despite methodological differences
      between our study and an earlier study, we believe that the previous findings
      were artifactual. One likely confounding element was the tendency of LcrH to
      adhere on its own to metal chelation chromatographic resin.

PMID- 9284178
TI  - Neutrophils play a critical role in early resistance to amebic liver abscesses in
      severe combined immunodeficient mice.
AB  - Animal models of liver abscess formation with Entamoeba histolytica suggest that
      the neutrophil is the first cell of the host immune system to interact with the
      invading ameba. In vitro studies have suggested that lysis of neutrophils by
      virulent amebae may exacerbate the damage seen in amebic liver abscesses. To
      investigate the role of neutrophils in vivo, we used the severe combined
      immunodeficient (SCID) mouse model of amebic liver abscess formation and compared
      liver damage in neutrophil-depleted and control mice. We found that neutrophil
      depleted animals have significantly larger amebic liver abscesses at early stages
      of infection and that abscesses in neutrophil-depleted SCID mice lack the
      prominent inflammatory cell ring seen in amebic liver abscesses in control SCID
      mice. These data suggest that neutrophils play a protective role in the early
      host response to amebic infection of the liver.

PMID- 9284181
TI  - A nonsubstituted primary hydroxyl group in position 6' of free lipid A is
      required for binding of lipid A monoclonal antibodies.
AB  - Lipid A monoclonal antibodies, which require for binding the presence of the
      bisphosphorylated D-glucosamine disaccharide lipid A backbone, were tested
      against synthetic lipid A precursor Ia and compound B 1047 by enzyme immunoassay.
      The last-named compound is a precursor Ia analog with a methoxy instead of a
      hydroxy group at C6' and was chosen to determine why these antibodies failed to
      recognize the bound lipid A present in lipopolysaccharide (LPS). Whereas all
      antibodies tested bound to precursor Ia, none of them bound to compound B 1047 or
      Escherichia coli Re LPS to a significant extent. Compared to the natural
      substituent at C6', i.e., 3-deoxy-D-manno-octulosonic acid (Kdo), the methoxy
      group is neither bulky nor charged. Thus, the data suggest that it is not
      hindrance by Kdo but rather the generation of a neoantigen that endows lipid A
      with immunoreactivity upon liberation from LPS by acid hydrolysis.

PMID- 9284180
TI  - A new restriction fragment length polymorphism from Cryptosporidium parvum
      identifies genetically heterogeneous parasite populations and genotypic changes
      following transmission from bovine to human hosts.
AB  - Length and restriction site polymorphism within a 2.8-kb threonine-rich open
      reading frame from Cryptosporidium parvum was identified and used to determine
      the genotypes of isolates from calves and humans. In agreement with observations
      of other genetic loci, all calf isolates were identical at this locus. In
      contrast, human isolates showed two profiles, one found exclusively in humans and
      one a superposition of both profiles, which were indicative of heterogeneous
      parasite populations. PCR fingerprints were consistent with a change in the
      genetic profile of C. parvum isolates following transmission from bovine to human
      hosts.

PMID- 9284182
TI  - A human monoclonal antibody which inhibits the coaggregation activity of
      Porphyromonas gingivalis.
AB  - A B-cell line producing a human monoclonal antibody (HuMAb) against a recombinant
      40-kDa outer membrane protein (OMP) of Porphyromonas gingivalis was constructed
      by in vivo immunization of a severe combined immunodeficiency C.B.-17/Icr mouse,
      which had been injected with human peripheral blood lymphocytes, with recombinant
      40-kDa OMP and subsequent Epstein-Barr virus immortalization of B cells isolated
      from the spleen of the mouse. This HuMAb inhibited coaggregation between P.
      gingivalis vesicles and Actinomyces naeslundii cells.

PMID- 9284183
TI  - A putative leucine zipper activator of Pasteurella haemolytica leukotoxin
      transcription and the potential for modulation of its synthesis by slipped-strand
      mispairing.
AB  - A Pasteurella haemolytica cosmid clone that activates leukotoxin transcription in
      Escherichia coli has been isolated. The activator locus, alxA, is part of a
      continuous open reading frame that includes the type I hsdM methylase gene. AlxA
      and HsdM peptides are processed from a precursor, and translation of the
      polyprotein can be modulated by slipped-strand mispairing across a
      pentanucleotide repeat, ACAGC, within the 5' end of alxA-hsdM. Extracts
      containing AlxA can bind to a leukotoxin promoter fragment.

PMID- 9284185
TI  - Case report of secondary megaprepuce.

PMID- 9284186
TI  - The missing alpha blocker paper.

PMID- 9284184
TI  - Listeriolysin and IrpA are major protein targets of the human humoral response
      against Listeria monocytogenes.
AB  - We have examined the human humoral immune response directed against proteins of
      Listeria monocytogenes in both healthy individuals and listeriosis patients. Two
      major targets for an antibody response were found in individuals that did not
      suffer from listeriosis: listeriolysin (Hly) and the recently described
      internalin-related protein (IrpA). In contrast, the humoral response in
      listeriosis patients appears to be more heterogeneous and included Hly, IrpA,
      InlB, and ActA as major targets.

PMID- 9284187
TI  - Resistive index in obstructive uropathy.

PMID- 9284188
TI  - The role of cigarette smoking in prostatic enlargement.
AB  - OBJECTIVE: To investigate the association between cigarette smoking and sex
      hormone concentrations in men with benign prostatic hyperplasia (BPH) and thus
      provide some understanding of the underlying mechanism of the effects of
      cigarette smoking on prostatic enlargement. PATIENTS AND METHODS: The association
      between cigarette smoking and prostatic volume was investigated in 68 men with
      BPH (mean age 59 years, range 52-74) by assessing changes in serum levels of
      oestradiol, testosterone, dihydroepiandrosterone (DHEA) and
      dihydroepiandrosterone sulphate (DHEA-S). Possible enzymatic mechanisms in the
      prostate gland that might be affected by cigarette smoking were assessed.
      RESULTS: The mean prostate volume was greater in non-smokers than smokers.
      Current cigarette smokers had significantly higher mean serum oestradiol levels
      than did the non-smokers (33.8 and 26.7 pg/mL, respectively, P < 0.01). Cigarette
      smoking was inversely but not significantly related to testosterone level. These
      differences persisted after adjusting for body mass index. There was no
      significant difference in serum DHEA and DHEA-S levels between smokers and non
      smokers. There was a weak correlation between the degree of prostatic
      enlargement, the presence of obstructive symptoms and urinary flow rates.
      CONCLUSION: These results indicate that cigarette smoking may affect the size of
      the enlarging prostate, but through indirect effects of smoking on factors
      provoking the development of BPH.

PMID- 9284189
TI  - The urological management of men with lower urinary tract symptoms, recorded
      using an interactive computer program.
AB  - OBJECTIVE: To analyse the level of agreement among urologists from the
      industrialized world in the management of men with lower urinary tract symptoms
      (LUTS). METHODS: Thirty-three urological departments participated in the study. A
      computer program was used to provide an unbiased format of 18 simulated cases of
      men with LUTS which individual urologists then evaluated diagnostically and made
      therapeutic decisions about their management. The management of the patients was
      assessed for the probability that a diagnostic test was used, that a therapy was
      offered to a particular patient, the first-choice therapies selected, the mean
      cost and range for the diagnostic process per patient and the number of first
      choice therapies offered by one urologist for all the patients. Various
      discriminators for these therapeutic decisions were evaluated, analysing the
      correlations between the information provided by the diagnostic tests and the
      probability of a particular therapy. RESULTS: For the 18 patients, the
      urologists, as a first choice, treated a mean (SD, range) of 8.3 (3.4, 3-16)
      patients with TURP, 3.9 (3.6, 0-11) with alpha-blockers, 2.3 (1.7, 0-6) with
      watchful waiting and 1.7 (2.4, 0-9) with finasteride. The other therapy options
      were only offered as a first choice by a few of the urologists in a few of the
      cases. The mean (SD, range) cost per patient of the diagnostic process was US$
      594 (209, 326-1350). CONCLUSION: There was considerable disagreement among the
      urologists about the management of men with LUTS, which included both the choice
      of diagnostic tests and the criteria for offering therapy to patients. If such
      disagreement prevails generally, it may be detrimental for the outcome of
      patients seeking medical attention for LUTS, and the cost of the medical care of
      these patients will be unnecessarily high.

PMID- 9284190
TI  - Quality-of-life assessment in patients after laser prostatectomy.
AB  - OBJECTIVE: To determine the importance of the assessment of quality of life in
      patients who have undergone laser prostatectomy. PATIENTS AND METHODS: Patients
      undergoing laser prostatectomy were evaluated using the International prostate
      symptom score (IPSS) questionnaire, uroflowmetry, post-void residual volume (PVR)
      measurements, and quality-of-life (QOL) and sexual function questionnaires.
      RESULTS: In all, 103 patients were evaluated; there was an overall significant
      improvement in the mean IPSS, maximum flow, PVR and QOL score and no apparent
      subjective change in sexual function. There was a good correlation between the
      IPSS and the QOL score, but no correlation between the QOL score and the maximum
      flow rate, and only a weak correlation between the IPSS and the maximum flow
      rate. CONCLUSION: Laser prostatectomy significantly changed the patients' quality
      of life. This may be more important for the patient than the improvement in the
      voiding variables alone. In future (changes in) quality of life will probably
      contribute significantly to selecting patients with voiding complaints for
      particular treatments.

PMID- 9284191
TI  - Uroflowmetry in women with urinary incontinence and pelvic organ prolapse.
AB  - OBJECTIVE: To characterize uroflowmetry parameters in women with pelvic organ
      prolapse (POP) and urinary incontinence (UI) and to assess the effects of
      clinical and urodynamic variables on these parameters. PATIENTS AND METHODS: The
      study comprised 655 consecutive women who presented with UI or POP and who had
      interpretable uroflowmetry values. Normal uroflowmetry values were defined as a
      maximum flow (Q(max)) > or = 15 mL/s, a mean flow (Q(mean)) > or = 10 mL/s, a
      post-void residual volume (PVR) < or = 100 mL and a continuous, single-peak
      waveform. Parametric and non-parametric analysis of variance and chi-square
      analysis were used to compare differences between diagnostic groups. Multiple
      linear regression models were developed to evaluate factors considered to
      influence uroflowmetry. RESULTS: Of the 655 patients, 471 (72%) had UI of whom
      16% had pure detrusor instability (DI), 69% pure genuine stress incontinence
      (GSI) and 15% with both, and 184 (28%) had POP, 26% of whom also had DI. Of all
      patients, 72% had normal uroflowmetry patterns, 13% had multiple peaks and 15%
      had patterns with interrupted flow; 56% had completely normal uroflowmetry. There
      were significant differences in uroflowmetry values between the POP and UI
      groups, with the former having a lower Q(max) and Q(mean) (P < 0.001), larger
      PVRs (P < 0.001) and a lower percentage of totally normal uroflowmetry (33% and
      64%, respectively, P < 0.001). Of patients with POP, 30% had a PVR > 100 mL.
      Because of the differences, the POP and UI groups were evaluated separately in
      the regression analysis. In both groups, the most important determinants of flow
      rate were the volume voided and pressure transmission ratio (PTR). However, when
      several factors (including age, voided volume, PTR and maximum detrusor pressure
      with flow and at Q(max)) were included in the model, they accounted for only 23
      26% of the variability of flow in the patients with UI and 36-39% of the
      variability in patients with POP. The subsets of patients with pure DI in both
      the UI and POP groups had higher PVR volumes than the other subsets. CONCLUSIONS:
      These results show that the positive correlation between flow rate and voided
      volume described in normal populations is also observed in women with UI and POP.
      However, most of the variability in urine flow was not attributable to factors
      such as age, voided volume and PTR, confirming the complexity of the micturition
      mechanism. Women with POP had more objective evidence of emptying-phase
      dysfunction than women with UI, although most emptied their bladders efficiently.
      Finally, the results suggest that women with DI exhibit dysfunction of both
      inhibitory and facilitory detrusor control.

PMID- 9284192
TI  - Differences in detrusor contractile function in women with neuropathic and
      idiopathic detrusor instability.
AB  - OBJECTIVE: To compare urodynamic indices of isometric and isotonic detrusor
      contractile function between patients with idiopathic detrusor instability and
      patients with multiple sclerosis (MS) and detrusor hyper-reflexia and thus
      determine whether the different types of detrusor instability share a common
      pathophysiological pathway. PATIENTS AND METHODS: Two groups of women were
      studied; 1139 neurologically normal patients with detrusor instability (mean age
      55 years, SD 17) and 141 with multiple sclerosis (MS) and detrusor hyper-reflexia
      (mean age 45 years, SD 11). Patients were assessed using static water cystometry,
      examining storage function, isometric and isotonic detrusor contractile function
      and voiding outflow function. RESULTS: Bladder capacities were lower in the MS
      group, with a median of 357 mL, 95% confidence interval (CI) 305-400 mL, compared
      with the neurologically normal patients (median 450 mL, 95% CI 425-450, P <
      0.001, Mann-Whitney U-test). Voiding was incomplete in the MS group, with a
      median (95% CI) residual volume of 100 (100-125) mL, but complete in the normal
      group, at 10 (10-10) mL. Higher median (95% CI) detrusor pressures at urethral
      opening (P(det open)) and closing (P(det close)) were recorded in the MS group
      than in the neurologically normal group, at 35.5 (33.2-46.6) cmH2O and 30 (27.6
      31.6) cmH2O for P(det open), respectively (P = 0.003), and 25.3 (20.9-31.6)cmH2O
      and 16.6 (15.0-18.1) for P(det close), respectively, (P = 0.001). In the MS
      group, the median (95% CI) isometric unstable contractions were less well
      maintained, but were more powerful, at 17.6 (15.6-18.9) N, compared to the
      neurologically intact group at 14.4 (14.0-14.9) N (P = 0.002). In the MS group,
      contractions frequently did not relax back to baseline, whereas in the group with
      detrusor instability, full relaxation after contraction was more usual. There was
      no significant difference in the maximum speed of detrusor shortening (isotonic
      activity), measured by the velocity constant Q*, between the groups (median for
      both groups 20 mL/s, 95% CI 17-23). CONCLUSION: These results show differences in
      storage function, isometric detrusor contractile function and voiding outflow
      function between detrusor instability and detrusor hyper-reflexia, indicating
      that the two conditions may not share a common pathophysiological pathway.

PMID- 9284193
TI  - The relationship of smooth muscle damage to age, severity of pre-operative
      hydronephrosis and post-operative outcome in obstructive uropathies.
AB  - OBJECTIVE: To determine the relationship, in patients with pelvi-ureteric
      junction (PUJ) obstruction, of histopathological abnormalities to their age at
      surgery, the severity of pre-operative hydronephrosis and the post-operative
      outcome. MATERIALS AND METHODS: Surgical specimens from 60 consecutive PUJ
      complexes excised at pyeloplasty were evaluated histologically. RESULTS: There
      was a close relationship of smooth muscle abnormality and fibrosis with the
      severity of pre-operative hydronephrosis and post-operative outcome, with no
      significant correlation between histopathological abnormality and patient age.
      CONCLUSION: This study appears to support the practice of the initial non
      operative management of congenital PUJ obstruction, potentially reducing the
      number of early and/or unnecessary interventions. Further investigations and
      research are necessary to direct appropriate management.

PMID- 9284194
TI  - The 'Queen Square bladder stimulator': a device for assisting emptying of the
      neurogenic bladder.
AB  - OBJECTIVE: To describe the effectiveness of a vibrating device for emptying the
      neurogenic bladder in patients with neurological disease. PATIENTS AND METHODS:
      The study involved 36 patients, comprising 29 with multiple sclerosis (MS), four
      with multiple system atrophy (MSA), one with radiation myelitis and two with
      neurological disease of uncertain aetiology. Most patients with MS (27) were able
      to walk unaided or with aids. Three of the 36 patients had loss of suprapubic
      sensation (two MS, one with uncertain diagnosis). All patients had free flow
      rates and ultrasonographic post-void residual volumes (PVRs) measured before and
      after voiding while using a vibrating device (frequency 60 Hz) applied to the
      suprapubic region. They also completed questionnaires about their urinary
      symptoms before and after the continued use of this device. The mean follow-up
      was 11.5 months (range 8-14). RESULTS: The device improved the symptoms in 25 of
      36 patients (70%) and reduced the PVR from a mean (standard deviation) of 175
      (78) mL to 68 (32) mL. It was not useful in patients with PVRs of > 400 mL,
      Kurtzke pyramidal function scores of > 3, and in those with suprapubic numbness.
      There were no complications and most patients complied well. CONCLUSIONS:
      Suprapubic vibration is an effective means of emptying the neurogenic bladder in
      patients who are not severely disabled and who have detrusor hyper-reflexia. It
      probably acts through a tonic vibration reflex which is under supraspinal
      influence. This device may be a useful alternative to clean intermittent self
      catheterization.

PMID- 9284195
TI  - Antioxidant deficiency following clam enterocystoplasty.
AB  - OBJECTIVE: To assess whether there is a reduction in serum antioxidant activity
      in patients who have undergone a clam enterocystoplasty procedure. PATIENTS AND
      METHODS: Serum glutathione peroxidase (GPase) activity was measured in 20
      patients who had undergone clam enterocystoplasty. Serum selenium concentration
      was also measured in 62 similar patients and compared with 56 healthy controls
      and 44 patients with a neuropathic bladder, mainly patients with spinal cord
      injuries who had not undergone surgery. RESULTS: GPase activity correlated well
      with serum selenium measurement. There was a significant reduction (P < 0.001) in
      serum selenium level in young (< 50 years old) non-neuropathic bladder patients
      following clam enterocystoplasty. This reduction in serum selenium was similar to
      that found in both unoperated patients with a neuropathic bladder (who are known
      to have an increased risk of developing bladder cancer) and those patients with a
      neuropathic bladder who had undergone augmentation. This reduction was not
      related to urinary tract infection nor the time since surgery. CONCLUSION: A
      reduction in serum selenium has been shown to increase susceptibility to bladder
      cancer following carcinogenic exposure to compounds such as nitrosamines. This
      study suggests that patients with idiopathic and congenital instability may be at
      an equally high risk as a result of undergoing this procedure.

PMID- 9284196
TI  - The staging pelvic lymphadenectomy: implications as an adjunctive procedure for
      clinically localized prostate cancer.
AB  - OBJECTIVES: To evaluate the utility of staging pelvic lymphadenectomy and to
      identify factors associated with nodal metastases in which a node dissection
      would be of clinical benefit. PATIENTS AND METHODS: A retrospective analysis
      (1989-1993) was performed on 303 consecutive patients who underwent staging
      bilateral modified pelvic lymph node dissection for clinically localized prostate
      cancer. Multivariate logistic regression analysis was used to evaluate age, race,
      clinical stage, prostate-specific antigen (PSA) level and Gleason score for
      predicting nodal metastases. RESULTS: Twenty-eight patients had nodal metastases,
      giving an overall prevalence of 9.2%. PSA and Gleason score (both P < 0.001) were
      significantly predictive of nodal involvement when combined or as independent
      variables. Relative to PSA and Gleason score, the patients' age, race and
      clinical stage were less relevant. Sensitivity analysis determined that combining
      a PSA of > or = 20 ng/mL (normal 0-4) and a Gleason score of > or = 8 gave a
      negative predictive value of 92% with a specificity of 99%, a positive predictive
      value of 67% and an overall accuracy of 91% for predicting nodal metastases.
      CONCLUSION: From this data, lymph node metastases are unlikely in patients with
      clinically localized prostate cancer who have a PSA of < 20 ng/mL and a Gleason
      score < 8, and that a pelvic lymph node dissection as an adjunctive procedure
      should be avoided in such individuals.

PMID- 9284197
TI  - Analysis of the local control in lymph-node staged localized prostate cancer
      treated by external beam radiotherapy, assessed by digital rectal examination,
      serum prostate-specific antigen and biopsy.
AB  - OBJECTIVE: To describe local disease control after radical external beam
      radiotherapy of prostatic carcinoma, as judged by digital rectal examination
      (DRE), transrectal ultrasonography (TRUS)-guided biopsies and estimates of serum
      prostate-specific antigen (PSA). PATIENTS AND METHODS: The study comprised 175
      patients (mean age 67.5 years, range 49-82; > 90% aged > or = 60 years) with
      localized prostatic carcinoma (T1-T3C, N0, M0) who underwent external beam
      radiation therapy (70 Gy), and were then regularly followed with a DRE,
      measurements of serum PSA and TRUS-guided biopsies to determine the outcome.
      RESULTS: The DRE revealed four patients with evidence of residual cancer in the
      prostate and biopsies showed no evidence of residual cancer in 131 (75%) of the
      patients. There was no correlation of residual cancer with tumour stage or grade
      but tumour size, as estimated by TRUS, correlated with the results of the biopsy.
      The nadir serum PSA level was < or = 1.0 ng/mL in 116 (66%) of the patients, of
      whom 76 (43%) had a nadir serum PSA level of < or = 0.5 ng/mL. The median time to
      the nadir level was 11 months. Serum PSA progression (> 4.0 ng/mL) at the latest
      PSA measurement after reaching the nadir occurred in 13% of the patients with a
      nadir PSA of < or = 0.5 ng/mL and in 25 of the 29 (86%) patients with a nadir
      serum PSA > 2.0 ng/mL. Cox regression analysis showed that tumour size and rectal
      irradiation dose were the most important factors for local control. CONCLUSIONS:
      Radiotherapy is effective in achieving local control in small prostate cancer
      tumours but less effective in large tumours. Tumour size and dorsal extension of
      the irradiated target, the rectal dose, were the two important factors for local
      control. A serum PSA level of < or = 1.0 ng/mL was associated with a higher
      chance of prolonged disease control.

PMID- 9284199
TI  - The in vitro effect of vitamin D3 analogue EB-1089 on a human prostate cancer
      cell line (PC-3).
AB  - OBJECTIVE: To determine the effect of vitamin D3 analogue (EB-1089) on the growth
      and proliferation of a prostate cancer cell line (PC-3). MATERIALS AND METHODS:
      PC-3 cells (10(4) cells per well) were plated into 24-well tissue culture plates.
      After 24 h, the culture medium was replaced with one containing the vitamin D3
      analogue EB-1089; a control treatment using only replacement medium was conducted
      in parallel. Cell proliferation was measured by the incorporation of 3H-thymidine
      7 and 12 days after the addition of the vitamin D3 analogue. Cells were
      precipitated with 5% trichloroacetic acid and the radioactivity determined using
      a scintillation counter. Each experiment was performed at least five times.
      RESULTS: There was a significant dose-dependent inhibition of cell growth after 7
      and 12 days of treatment with EB-1089, varying from 40 to 70% of the 3H-thymidine
      incorporation by controls, respectively. The maximum inhibition occurred with 0.1
      micromol/L EB-1089 on day 7 and day 12 (both P < 0.01). Longer incubation times
      appeared to have a greater effect when higher concentrations of EB-1089 were
      used. CONCLUSION: These in vitro studies have shown that the vitamin D3 analogue
      EB-1089 can significantly reduce the growth rate of the prostate cancer cell line
      PC-3. This would support the hypothesis that deficiency of vitamin D increases
      the risk of prostate cancer and further in vivo testing of vitamin D is warranted
      for its potential role in active therapy.

PMID- 9284198
TI  - Serum free prostate-specific antigen in the diagnosis of prostate cancer.
AB  - OBJECTIVE: To determine the value of the ratio of free prostate-specific antigen
      (fPSA) to total PSA (tPSA) in the diagnosis of benign prostatic hyperplasia (BPH)
      and prostate cancer in a cohort of patients undergoing prostatic transrectal
      ultrasonography (TRUS). PATIENTS AND METHODS: The study comprised 153 patients
      (99 with BPH and 54 with prostate cancer) undergoing diagnostic TRUS of the
      prostate. Patients with a tPSA of > 30 ng/mL were excluded from analysis. Free
      PSA was assayed using an immunoassay specific for unbound PSA (CanAg Diagnostics,
      Sweden). Total PSA was measured using the HybriTech Tandem-R PSA
      immunoradiometric assay in routine clinical use and this estimate was validated
      using the CanAg tPSA assay. RESULTS: The measurements of tPSA from both assay
      systems correlated closely. The f/tPSA ratios in patients with prostate cancer
      were significantly lower than in those with BPH (median values 0.152 and 0.2,
      respectively, P<0.01). In patients with prostate cancer, the median f/t PSA
      levels apparently declined with increasing tPSA levels but in those with BPH, the
      levels of tPSA were not significantly associated with the f/tPSA ratio; the
      ratios did not vary significantly with age in either group. A f/tPSA ratio at a
      threshold of 0.16 had positive and negative predictive values of 44% and 74%,
      respectively; the corresponding values for a tPSA of > 4 ng/mL were 30% and 52%.
      CONCLUSION: The f/tPSA ratio differs significantly between patients with BPH and
      cancer but because there is a considerable overlap of f/tPSA ratios between the
      groups, f/tPSA values alone were not sufficiently specific to be used as a single
      diagnostic test.

PMID- 9284200
TI  - Detection of telomerase activity in human prostate: a diagnostic marker for
      prostatic cancer?
AB  - OBJECTIVE: To assess the role of telomerase activity as a marker for the
      development of prostate cancer in men with existing benign prostatic hyperplasia
      (BPH), a known risk factor for prostatic carcinoma. MATERIALS AND METHODS:
      Telomerase activity was assayed, using a highly sensitive polymerase-chain
      reaction-based assay, in nine biopsies from patients with prostatic cancer, 16
      from patients clinically diagnosed with BPH and 11 from patients with no evidence
      of prostatic disease. RESULTS: Telomerase activity was detectable in eight of the
      nine prostate cancer biopsies, in none of the normal prostates and in six of the
      16 BPH biopsies. CONCLUSION: The finding of telomerase activity in six of 16
      biopsies from patients with BPH could indicate early prostate cancer and suggests
      that telomerase activity may be of use as a biomarker in patients diagnosed with
      BPH and who may subsequently develop prostate cancer.

PMID- 9284201
TI  - Tumour size measured by transrectal ultrasonography in the staging of prostate
      cancer before radical prostatectomy.
AB  - OBJECTIVE: To assess the diagnostic accuracy of transrectal ultrasonography
      (TRUS) in predicting the local extent of prostate cancer before radical
      prostatectomy. PATIENTS AND METHODS: From April 1990 to April 1993, 59
      consecutive patients (mean age 63 years, range 49-71) with clinically localized
      prostate cancer were examined using TRUS before radical prostatectomy. Primary
      tumours were clinically categorized according to the TNM classification and
      biopsies graded histologically. Tumour size was measured as length on a
      longitudinal and height and width on a transverse ultrasonogram. The results from
      TRUS were compared with those from the histopathological examination of whole
      mount step sections of the surgical specimens. RESULTS: In 50 patients, TRUS
      using standard criteria achieved sensitivity, specificity, positive- and negative
      predictive values (PPV, NPV) of 0.47, 0.63, 0.73 and 0.36, respectively, in
      predicting pathological stage. Dimensions were obtained from 45 patients with
      hypoechoic tumours; in a multivariate linear discriminant analysis the TRUS
      estimate of width was the best predictor of pathological stage. The sensitivity,
      specificity, PPV and NPV for tumour width from TRUS, using a threshold of 19 mm,
      were 0.42, 0.93, 0.93 and 0.43, respectively. CONCLUSION: Tumour width measured
      by TRUS may improve the assessment of the local extent of prostate cancer.

PMID- 9284202
TI  - Serum pyridinoline crosslinks as markers of tumour-induced bone resorption.
AB  - OBJECTIVE: To assess serum pyridinoline (Py) and deoxypyridinoline (dPy), using a
      new high-performance liquid chromatography (HPLC) method, as a serum marker to
      determine the incidence of metastatic bone disease in an animal model and in the
      monitoring of patients with or without metastatic bone disease from prostate
      cancer and renal cell carcinoma (RCC). PATIENTS, MATERIALS AND METHODS: Female
      C3H/He mice (8-12 weeks old) received a subcutaneous injection of tumour-cell
      suspensions of serially transplanted MBT tumours. The tumour cells induced
      osteolysis associated with osteoclast proliferation and serum samples were
      evaluated for Py and dPy using HPLC. The growth of the tumour macroscopically and
      histologically, and the extent of bone loss assessed by radiography, were
      compared with the serum Py and dPy level. In the clinical study, patients with or
      without bone metastases from RCC (24 patients) or prostate cancer (37 patients)
      were monitored using the same techniques and the number and extent of bone
      metastases compared with serum Py and dPy levels both in these patients and in 84
      healthy control subjects. RESULTS: There was a significant correlation between
      the bone loss evaluated by radiography and the level of serum Py in the animal
      model. Patients with bone metastases from RCC had higher values of Py and dPy
      than patients without known metastatic bone disease. The serum Py level increased
      in two patients as metastatic bone disease progressed. Similarly, in patients
      with prostate cancer, the mean level of serum Py and dPy was higher in patients
      with bone metastasis than in the control group, and also higher than that in
      patients without metastases. The serum Py and dPy levels could also distinguish
      patients with metastatic bone disease with and without a lytic component.
      CONCLUSION: Measurements of serum Py appear to provide a good index of increased
      bone resorption induced by experimental tumours and in patients with bone
      metastases from RCC and prostate cancer.

PMID- 9284203
TI  - Neuroendocrine stains and proliferative indices of prostatic adenocarcinomas in
      transurethral resection samples.
AB  - OBJECTIVE: To determine whether the quantification of certain neuroendocrine and
      proliferative markers would help in the prognostic evaluation of prostatic
      adenocarcinomas obtained during transurethral resection of the prostate (TURP).
      MATERIALS AND METHODS: Samples from two groups of patients with prostate cancer
      were examined. One group comprised 23 patients, of whom 12 were stage IV and 11
      stage III, all with Gleason scores of > or = 7; this group was designated as high
      grade, high-stage (HGHS). The second group comprised 10 consecutive patients with
      stage T1a adenocarcinoma of the prostate with Gleason scores of < or = 6,
      designated as low-grade, low-stage (LGLS) tumours. Tumour tissue from each TURP
      was stained with MIB-1 (an indicator of cell proliferation), neuron-specific
      enolase (NSE), chromogranin A (ChA) and synaptophysin (Syn), and 1000 cells
      counted to determine the percentages of positive cells in both benign and
      malignant tissue. The percentage of MIB-1-positive cells was designated as the
      proliferative index (PI). Patients were clinically followed to evaluate tumour
      progression, documented by rising prostate-specific antigen (PSA) levels, X-ray
      evidence of recurrent or metastatic carcinoma, or tissue biopsy showing
      malignancy. RESULTS: The mean number of neuroendocrine cells (NEC) for each
      marker and the mean PI were greater in the HGHS tumours than in the LGLS tumours
      or surrounding benign tissue of either group (P < 0.01). The LGLS tumours were
      remarkable for a having mean PI of about twice that of the benign tissue (2.9 and
      1.3, respectively, P < 0.01); the NEC in these cases were more frequent in the
      benign than in the malignant tissue. There was no significant difference between
      the mean PIs and the mean percentages of NEC in the 14 HGHS tumours that
      progressed and the nine HGHS tumours that did not (P values 0.37-0.96).
      CONCLUSIONS: Although the PI assessed by MIB-1 and the number of NEC-positive
      cells were much higher in HGHS than LGLS tumours, this finding did not appear to
      have independent prognostic significance. The significance of the higher PI in
      LGLS tumours than in corresponding benign tissue is uncertain; LGLS tumours had
      fewer NEC than the surrounding benign tissue. The quantification of any of these
      four markers (MIB-1, NSE, ChA, Syn) was not prognostically helpful in these
      groups of cancers present in TURP specimens.

PMID- 9284204
TI  - Neuroendocrine differentiation and prognosis in prostatic adenocarcinoma.
AB  - OBJECTIVES: To assess the prognostic importance of neuroendocrine differentiation
      in conventional (non-small cell) prostatic adenocarcinoma. MATERIALS AND METHODS:
      Ninety-two samples from patients with prostatic adenocarcinoma were studied
      retrospectively. The immunohistochemical analysis of chromogranin A and neuron
      specific enolase in formalin-fixed, paraffin wax embedded prostatic tissue chips
      was related to other prognostic variables and patient survival. RESULTS:
      Neuroendocrine differentiation was detected in 48 cases; there was a significant
      correlation with worsening tumour differentiation, the presence of bone
      metastases and with worsening survival, but no independent effect of
      neuroendocrine differentiation on survival. CONCLUSION: The detection of
      neuroendocrine differentiation in conventional prostatic adenocarcinoma is not an
      independent indicator of prognosis.

PMID- 9284205
TI  - Co-localization of nitric oxide synthase, neuropeptides and tyrosine hydroxylase
      in nerves supplying the human post-natal vas deferens and seminal vesicle.
AB  - OBJECTIVE: To determine the distribution and patterns of co-localization of
      nitric oxide synthase (NOS), neuropeptides and tyrosine hydroxylase (TH) in
      intrinsic nerves of the human post-natal vas deferens and seminal vesicle.
      MATERIALS AND METHODS: Double and triple immunolabelling methods were used in
      tissue from 10 male infants and children (age range 2 months to 3 years) obtained
      at post-mortem examinations carried out within 12 h of death. RESULTS: Most
      nerves supplying the muscle coat of either organ were TH-immunoreactive (-IR),
      most of which also contained neuropeptide Y (NPY) while a smaller proportion
      contained both NPY and NOS. Minor populations of the TH/NPY-IR intramuscular
      nerves contained calcitonin gene-related peptide (CGRP), galanin (GAL), met
      enkephalin (m-ENK) or vasoactive intestinal polypeptide (VIP). Non-TH-IR
      intramuscular nerves were relatively infrequent and most contained NPY and either
      VIP or NOS. Presumptive secretomotor nerves formed subepithelial plexuses in both
      organs, most of which contained NPY co-localized with either VIP or NOS, with
      minor populations containing CGRP and/or GAL. TH- and substance P (SP) -IR nerves
      were not observed subepithelially. Perivascular nerve plexuses were mainly formed
      by TH-IR varicose nerves, most of which contained co-localized NPY and CGRP, with
      a smaller proportion containing NPY and NOS and minor populations containing VIP,
      m-ENK, SP or GAL. CONCLUSION: These results indicate that the autonomic control
      of the human vas deferens and seminal vesicle is provided by several
      immunohistochemically distinct nerve populations. Furthermore, NOS is present in
      a proportion of both the noradrenergic and non-noradrenergic nerves.
      Pharmacological studies are now required to elucidate the precise roles of nitric
      oxide and neuropeptides in the functional control of these organs.

PMID- 9284207
TI  - Carcinoma of the penis--appraisal of a modified tumour-staging system.
AB  - OBJECTIVE: To evaluate variables for the prediction of lymph node metastases in
      carcinoma of the penis, using a recently proposed modified tumour-staging system
      that combines the histological degree of differentiation and extent of local
      invasion of the primary tumour. PATIENTS AND METHODS: Thirty-five patients with
      squamous carcinoma of the penis and histo- or cytological staging of the inguinal
      lymph nodes were reviewed. A clinical TNM staging system was used in which the
      size (diameter) of the primary tumour and the clinical extent of invasion were
      considered. Subsequently, the tumours were also staged according to a modified T
      system in which the histological degree of differentiation and pathological
      extent of tumour invasion were combined. RESULTS: Penectomy was performed in 34
      patients (partial amputation in 20 and radical penectomy in 17). Inguinal
      lymphadenectomy was performed in 31 patients and in four the presence of lymph
      node metastases was confirmed by aspiration cytology. Using the clinical TNM
      staging system, lymph node metastases were histo- or cytologically present in no
      patients with T1, in five of 19 with T2, in 10 of 13 with T3 and in both patients
      with T4 tumours. Lymph node metastases were present in two of eight patients
      without clinically palpable inguinal nodes, in three of 14 with nodes clinically
      thought to be infective and in 11 of 12 nodes clinically considered to be
      malignant. Lymph node metastases were present in five of 17 patients with grade
      1, in nine of 13 with grade 2 and in three of five with grade 3 tumours. Using
      the modified histological T-staging system (T1 = grade 1-2, invasive through
      dermis; T2 = any grade, invasion of corpus spongiosum or cavernosum; T3 = any
      grade, invasion of urethra; T4 = grade 3, regardless of invasion) lymph node
      metastases were present in one of nine patients with T1, in eight of 16 with T2,
      in all five with T3 and in three of five with T4 tumours. CONCLUSION: The
      modified T-staging system, which combines histological differentiation with
      pathological extent of invasion, provided the best predictive distinction between
      T1 and T2-4 tumours, indicating that lymphadenectomy can be avoided in T1
      tumours, but should be performed in all patients with T2-4 tumours. We recommend
      bilateral inguinal lymphadenectomy 6-8 weeks after penectomy in such patients.

PMID- 9284206
TI  - mRNA and protein expression of nitric oxide synthase and adrenoceptor alpha 1 in
      young and old rat penile tissues.
AB  - OBJECTIVE: To investigate alterations of neuronal structure and the mRNA
      expression of nitric oxide synthase (NOS) and adrenoceptor alpha 1 in young and
      old rat penile tissues, and assess the importance of these factors in erectile
      dysfunction (ED) associated with ageing. MATERIALS AND METHODS: NOS was
      determined in the pelvic ganglia of 32 rats using nicotinamide adenine
      dinucleotide phosphate (NADPH)-diaphorase staining. Adrenergic neurons were
      identified by histofluorescence staining. The gene expression for NOS and for
      adrenoceptor alpha 1 was investigated in corporal tissue by differential reverse
      transcriptase-polymerase chain reaction (RT-PCR) using specific oligonucleotide
      primers. b-actin was used as an internal standard in each tube to quantify the
      baseline gene expression. RESULTS: The following changes occurred in old rats:
      (i) an increase of lipofuscin and a decrease in both bNOS-containing neurons and
      fluorescent adrenergic neurons in the pelvic ganglia; (ii) significantly less
      expression of NOS mRNA than in young rat penile tissues; and (iii) no significant
      alteration in adrenoreceptor alpha 1 mRNA expression. CONCLUSIONS: The fewer
      adrenergic and NOS-containing neurons and neurotransmitters in pelvic ganglia
      from old rats may explain the enhanced penile smooth muscle tone previously
      reported in older impotent men. Furthermore, lower mRNA expression of NOS may be
      associated with structural and functional changes associated with ageing penile
      tissue.

PMID- 9284208
TI  - Renal Doppler ultrasonography in children with equivocal obstructive uropathy:
      effect of intravenous normal saline fluid load and frusemide.
AB  - OBJECTIVE: To study the effect of hyperhydration with normal saline and frusemide
      on the renal resistive index (RI) in children with equivocal obstructive
      uropathy. PATIENTS AND METHODS: Twelve children (24 kidneys) with unilateral or
      bilateral hydronephrosis underwent isotopic diuretic renography and Doppler
      ultrasonography. All children had equivocal obstruction of the hydronephrotic
      kidneys with half-time drainage (T/2) values of 10-20 min. Doppler studies were
      carried out both at baseline and after the infusion of normal saline and
      frusemide. RESULTS: Of the 24 kidneys, five were normal and 19 were
      hydronephrotic; compared with normal kidneys, the hydronephrotic units had a
      significantly lower glomerular filtration rate (GFR) and longer T/2. At baseline,
      the mean RI values of normal and hydronephrotic kidneys were not significantly
      different (0.70, SD 0.03 and 0.71, SD 0.04, respectively). After the infusion of
      saline and frusemide, the mean RI of hydronephrotic kidneys (0.67, SD 0.07) was
      significantly (P = 0.01) higher than that of normal kidneys (0.60, SD 0.02), but
      the response of RI in hydronephrotic kidneys was variable. Based on the RI at
      baseline and after infusion, hydronephrotic kidneys could be categorized into
      three groups. Group 1 (n = 6) had an RI < 0.7 before and after infusion, group 2
      (n = 6) had a baseline RI > 0.7 and < 0.7 after infusion, and in group 3 (n = 7)
      both RIs were > 0.7. Kidneys in group 3 had the lowest GFR and the highest T/2
      values. Five of these seven hydronephrotic kidneys eventually had deteriorating
      GFRs requiring surgical correction; the GFR of the remaining hydronephrotic
      kidneys remained stable. CONCLUSION: In children with equivocal obstructive
      uropathy based on diuretic renography, the determination of RI before and after
      infusion of normal saline and frusemide could be helpful in distinguishing
      obstructed from non-obstructed kidneys.

PMID- 9284210
TI  - Buccal mucosal graft for secondary hypospadias repair and urethral replacement.
AB  - OBJECTIVE: To assess the effectiveness of buccal mucosa in the treatment of
      complex hypospadias. PATIENTS AND METHODS: Seventeen patients had an onlay patch
      of buccal mucosa to reconstruct the urethra after failed previous surgery; five
      had a tubed buccal mucosal graft as an urethral replacement in the 'primary'
      repair of severe hypospadias. RESULTS: There were no complications in 19
      patients; two developed fistulae and one a stricture due to graft narrowing.
      There were no meatal complications. CONCLUSION: Buccal mucosa taken from the
      inner aspect of the lip is very suitable for reconstructing a failed hypospadias
      repair, especially when used as an onlay graft.

PMID- 9284209
TI  - The characteristics of primary vesico-ureteric reflux in male and female infants
      with pre-natal hydronephrosis.
AB  - OBJECTIVE: To examine the characteristics of primary vesico-ureteric reflux (VUR)
      in young infants following prenatal hydronephrosis. PATIENTS AND METHODS: The
      study comprised 155 consecutive infants with VUR detected at a mean age of 8.7
      weeks (SD 6.3). Reflux units (n = 236) were analysed for relationships between
      gender, severity of reflux, exposure to urinary tract infection (UTI) and the
      presence of focal and generalized types of kidney damage on imaging. Bladder wall
      thickness (from ultrasonography) was examined in comparison with a further group
      of 29 males without VUR. RESULTS: Male infants predominated (117 of 155, 75%);
      bilateral VUR affected the same proportion (52%) of males and females. Most
      kidneys exposed to VUR (158 of 236. 67%) were normal and of the 78 abnormal
      kidneys (57 without UTI), 53 showed generalized damage (only eight exposed to
      UTI) and 71 (91%) were associated with severe (grades IV and V) reflux that
      predominantly affected males (P < 0.001). Grade V reflux was almost exclusively a
      male disorder. Most female units (45 of 58, 78%) compared with 46% (82/178) of
      male units had mild (grades I to III) reflux that was independently associated
      with normal kidneys. The mean bladder wall thickness was significantly greater
      for males with VUR than for females with VUR and for males without VUR.
      CONCLUSIONS: Two distinct but not exclusive patterns of VUR were identified: (i)
      mild reflux associated with normal kidneys that affected most females and a
      proportion of males; (ii) severe reflux combined with kidney damage, most likely
      fetal in origin, that is almost exclusively a male disorder.

PMID- 9284211
TI  - High scrotal orchidopexy for palpable maldescended testes.
AB  - OBJECTIVE: To confirm that most spermatic cords of palpable maldescended testes
      are long enough to place the testes in the scrotum and therefore that a
      satisfactory scrotal testicular position can be achieved by a single high scrotal
      incision with less dissection of the inguinal region. PATIENTS AND METHOD:
      Between January 1991 and June 1995, 106 high scrotal orchidopexies (HSOs) for
      clinically palpable maldescended testes were carried out in 96 patients (mean age
      41 months, range 14 months to 11 years). Ten patients had bilateral undescended
      testes. Regardless of the initial testicular position or the age of the patients,
      all orchidopexies were commenced with a high scrotal incision. Ninety-two testes
      (87%) were placed satisfactorily in the scrotum and the remaining 14 testes (13%)
      required a second inguinal incision. RESULTS: During the follow-up (mean 16
      months, range 8 months to 3 years), 85 testes (80%) showed good anatomical and
      cosmetic results. Five testes required a repeat conventional orchidopexy 6 months
      after the HSO. Three testes were excised because they showed atrophic changes; 11
      of the 14 testes which required two incisions initially have shown good results.
      CONCLUSION: High scrotal orchidopexy is a satisfactory approach to any palpable
      maldescended testis, having the advantage of using a single incision and
      requiring less dissection and anatomical disruption of the inguinal region, with
      excellent cosmesis.

PMID- 9284212
TI  - Impact of early orchidopexy on testicular growth.
AB  - OBJECTIVE: To assess the impact of early orchidopexy on post-operative testicular
      growth. PATIENTS AND METHODS: One-hundred and ninety boys (age range 1 week to 15
      years at the time of initial diagnosis) underwent surgery for the repair of
      unilateral cryptorchidism, and the relative testicular size was assessed before
      and after operation. RESULTS: When compared with the size of the uninvolved
      testis, testicular size increased after surgery in 11.6% of cases and decreased
      in 2.6%. Testicular growth was more common among children operated when younger
      than 18 months (P = 0.016) than when older. CONCLUSION: The testicle may grow
      when orchidopexy is performed in children younger than 18 months.

PMID- 9284214
TI  - Laparoscopic removal of an electric wire from the bladder.

PMID- 9284213
TI  - A simplified stapling technique for securing the dorsal vein complex.

PMID- 9284215
TI  - Enucleation of renal cell carcinoma in an allograft kidney 21 years after
      transplantation.

PMID- 9284217
TI  - Bellini duct carcinoma of the kidney.

PMID- 9284216
TI  - Treatment of intermittent idiopathic priapism with oral terbutaline.

PMID- 9284218
TI  - Malignant mesothelioma of the tunica vaginalis testis: an immunohistochemical and
      ultrastructural study of two cases.

PMID- 9284219
TI  - Penile necrosis following cholesterol embolism.

PMID- 9284220
TI  - Laparoscopic post-chemotherapy retroperitoneal dissection of residual mass.

PMID- 9284223
TI  - Chlamydial epididymitis presenting as a solid asymptomatic scrotal mass.

PMID- 9284222
TI  - Squamous cell carcinoma in a patient on clean intermittent self-catheterization.

PMID- 9284221
TI  - Percutaneous vascular control for inferior vena cava thrombectomy.

PMID- 9284224
TI  - Obstruction of the lower ureter caused by an aberrant vessel.

PMID- 9284225
TI  - Secondary megaprepuce.

PMID- 9284226
TI  - Secondary megaprepuce.

PMID- 9284227
TI  - Secondary megaprepuce.

PMID- 9284228
TI  - Secondary megaprepuce.

PMID- 9284230
TI  - Finasteride plus flutamide for prostatic carcinoma.

PMID- 9284229
TI  - Secondary megaprepuce.

PMID- 9284231
TI  - Retrograde balloon dilatation for primary pelvi-ureteric stenosis.

PMID- 9284233
TI  - Facilitatory effect of thinking about movement on magnetic motor-evoked
      potentials.
AB  - To investigate the facilitatory effect of thinking about movement on motor evoked
      potential (MEP) amplitude, we recorded MEPs in two test muscles during rest, with
      the subject thinking about contracting the test muscle but without subsequent
      contraction, and during 10% maximum voluntary contraction. Stimuli were delivered
      at 10% above resting motor threshold and at 90-100% stimulator output. H
      reflexes, recorded in flexor carpi radialis, were obtained during rest and think
      conditions. MEP threshold was lower during the think condition (P = 0.004). At
      both stimulus intensities, median MEP amplitudes and areas were significantly (P
      < 0.001) larger during the think paradigm compared with rest. This effect was
      greater at the lower stimulus intensity. There was no significant difference in
      latency (P = 0.15). In 4/8 subjects, H-reflex amplitudes were mildly facilitated
      (P < 0.05) during the think condition. We conclude that thinking about movement
      without detectable EMG activity has a facilitatory effect on magnetic MEPs. The
      absence of a MEP latency shift between rest and think conditions and absence of a
      consistent increase in H-reflex amplitude suggests this effect occurs largely at
      the cortical level. In some subjects, however, an increase in spinal motoneuron
      excitability may also contribute.

PMID- 9284232
TI  - Temporal changes of pyramidal tract activities after decision of movement: a
      study using transcranial magnetic stimulation of the motor cortex in humans.
AB  - To elucidate the effects of the decision to move on the pyramidal tract in
      humans, we examined the changes in the motor evoked potentials (MEP) of the
      forearm muscles following transcranial magnetic cortical stimulation (TMS) of the
      hand area during a go/no-go hand-movement task in 10 normal subjects. The
      subjects performed an extension of the right wrist according to the go, no-go and
      control signals, one of which was randomly presented on a TV. A single TMS was
      applied to the primary hand motor area in the left hemisphere 0-300 ms after each
      signal. The MEPs recorded from the wrist extensor and flexor muscles changed in
      amplitude after both go and no-go signals. In comparison with the control, the
      MEPs were significantly facilitated in the agonistic muscles (wrist extensor
      muscles) and attenuated in the antagonistic muscles (wrist flexor muscles), at
      the latencies of 100-200 ms after the go signal (P < 0.02). In contrast, the MEPs
      of both the extensor and flexor muscles were significantly attenuated during the
      period of 100-200 ms after the no-go signal (P < 0.001). We speculate that there
      is strong inhibition on the pyramidal tract after the no-go signal and that the
      inhibitory effect is non-specific to the target muscles. This inhibition differs
      from the reciprocal inhibition of the MEP observed in antagonistic muscles after
      the go signal, and it is probably related to the movement decision originating in
      the prefrontal cortex.

PMID- 9284234
TI  - Reversible changes of motor cortical outputs following immobilization of the
      upper limb.
AB  - We mapped the cortical representations of the abductor pollicis brevis, flexor
      carpi radialis, biceps and deltoid muscles in six subjects with unilateral wrist
      fractures, immediately after the removal of the splint. This was repeated 1 month
      later in three out of the six subjects. Duration of immobilization was 1 month.
      Muscle maps were obtained by delivering four focal magnetic pulses for each scalp
      position (1 cm apart with reference to Cz) over the contralateral hemisphere.
      Motor evoked potentials (MEPs) were averaged off-line and expressed as a
      percentage of the motor action potential evoked by supramaximal peripheral nerve
      stimulation. Volume, area and threshold of the motor maps showed no significant
      hemispheric differences within each muscle in 10 control subjects. In the first
      recording session the volume of each immobilized muscle was distinctly higher
      when compared to that of controls in terms of absolute value and side-to-side
      ratio. This finding disappeared 1 month later. Moreover, MEP amplitude difference
      recorded from hand muscle could be reversed during a small tonic voluntary
      contraction. Immobilization had no significant effect on the threshold for
      activation of the target muscles and on the area of the motor map. The increase
      in MEP amplitudes occurred without changes in spinal excitability as tested by
      the F wave. These findings suggest that immobilization of the upper limb induces
      a reversible enhancement of the excitability of structures along the
      corticomotoneuronal pathway. Sustained restriction of volitional movements and
      reduction in somatic sensory inputs might promote this functional modulation of
      the motor system.

PMID- 9284235
TI  - Crossed and direct effects of digital nerves stimulation on motor evoked
      potential: a study with magnetic brain stimulation.
AB  - We studied the influence of contralateral and ipsilateral cutaneous digital nerve
      stimulation on motor evoked potentials (MEPs) elicited in hand muscles by
      transcranial magnetic stimulation (TMS). We tested the effect of different
      magnetic stimulus intensities on MEPs recorded from the thenar eminence (TE)
      muscles of the right hand while an electrical conditioning stimulus was delivered
      to the second finger of the same hand with an intensity four times above the
      sensory threshold. Amplitude decrement of conditioned MEPs as a function of
      magnetic stimulus intensity was observed. The lowest TMS stimulus intensity
      produced the largest decrease in conditioned MEPs. Moreover, we investigated the
      effects of ipsilateral and contralateral electrical digital stimulation on MEPs
      elicited in the right TE and biceps muscle using an intensity 10% above the
      threshold. Marked MEP inhibition in TE muscles following both ipsilateral and
      contralateral digital stimulation is the main finding of this study. The decrease
      in conditioned MEP amplitude to ipsilateral stimulation reached a level of 50% of
      unconditioned MEP amplitude with the circular coil and 30% with the focal coil.
      The amplitude of conditioned MEPs to contralateral digital stimulation showed a
      decrease of 60% with the circular coil and more than 50% with the focal coil. The
      onset of the inhibitory effect of contralateral stimulation using the focal coil
      occurred at a mean of 15 ms later than that of ipsilateral stimulation. No MEP
      inhibition was observed when recording from proximal muscles. Ipsilateral and
      contralateral digital stimulation had no effect on F wave at appropriate
      interstimulus intervals, where the main MEP suppression was noted. We stress the
      importance of selecting an appropriate test stimulus intensity to evaluate MEP
      inhibition by digital nerves stimulation. Spinal and cortical sites of
      sensorimotor integration are adduced to explain the direct and crossed MEP
      inhibition following digital nerves stimulation.

PMID- 9284236
TI  - Magnetic transcranial stimulation: clinical interest of the silent period in
      acute and chronic stages of stroke.
AB  - There is little information on the silent period during facilitation of the
      target muscle at the acute stage of stroke and the ultimate clinical status. We
      studied 69 subjects with transcranial magnetic stimulation: 20 matched controls
      and 49 hemiparetic patients investigated 7 and 90 days after the stroke (D7,
      D90). We measured the silent period duration (SPD) in the first dorsal
      interosseous muscle at 10 and 100% of maximal voluntary isometric contraction
      (VIC). The SPD index (the ratio of SPD at VIC 100% by SPD at VIC 10%) at D7 was
      matched with the clinical outcome at D90. Two patterns of responses could be
      determined at D7. In the normal subjects and in 27 out of 32 patients who
      eventually recovered satisfactory function at D90, the SPDs were stable during
      facilitation (SPD index 100%). On the contrary, in 10 out of the 17 patients with
      a poor functional outcome, the mean SPD decreased when VIC was increased (SPD
      index 80%); besides, their muscle tone was significantly increased at D90.
      Similar patterns were still present in the patients at D90: the mean SPD indexes
      were not significantly different from D7. We conclude that in the early stage of
      stroke, a low SPD index appears to be correlated with the eventual occurrence of
      spasticity.

PMID- 9284237
TI  - Magnetic stimulation study in patients with myotonic dystrophy.
AB  - To further define motor nervous system alterations in myotonic dystrophy (MD),
      motor potentials to transcranial and cervical magnetic stimulation (MEPs) were
      recorded from the right abductor pollicis brevis muscle in 10 patients with MD
      and in 10 healthy controls. Cortical and cervical latencies, central motor
      conduction time (CMCT), stimulus threshold intensity and cortical MEP amplitudes
      expressed both as absolute values and as %M were analysed. MEP cervical latency,
      absolute or relative amplitude and excitability threshold did not significantly
      differ in patients and controls. The mean cortical motor latency and CMCT were
      significantly prolonged in MD patients with respect to normal subjects. Moreover,
      CMCTs were found to be significantly related to stimulus threshold intensity (P =
      0.03) and only marginally related to absolute cortical amplitude (P = 0.06).
      These findings are indicative of a central motor delay, also related to decreased
      excitability of motor neurons, in patients with MD. No correlations were found
      between individual neurophysiological parameters and age, duration of disease and
      clinical impairment. Our results suggest that magnetic stimulation studies can
      detect subclinical dysfunctions of the central motor system in MD patients, as
      one of the multisystemic manifestations of the disease, rather independent of the
      primitive muscle damage.

PMID- 9284238
TI  - Relationship between the degree of inhibited stretch reflex activities of the
      wrist flexor and reaction time during quick extension movements.
AB  - It has been reported that stretch reflex responses, including the long latency
      component, are modulated by motor preparation for the direction and type of
      movement. In the present study, human subjects were required to make a reaction
      movement in the direction of the wrist extension following a muscle stretch to
      the wrist flexor, and we investigated the relationship between the modulation of
      reflex activities of the wrist flexor and the length of reaction time (premotor
      time) of the wrist extensor. Twenty-five healthy males, ranging in age from 20 to
      28, participated in the experiments. A DC torque motor was used to evoke the
      reflex EMG responses on the flexor. Averaging the rectified EMG, recorded with
      the surface electrodes over the flexor, showed short and long latency reflexes
      (M1 and M2 components) in response to the muscle stretch. For all subjects, the
      amplitudes of the reflex components during the extension reaction movement
      decreased, compared to those amplitudes in the non-reaction tasks. The decrease
      in the M2 component, which is considered a transcortical reflex, was
      significantly larger than the decrease in the M1 component, which is a spinal
      reflex. Moreover, there were correlations between reaction time to muscle stretch
      and the degree of decrease in reflex activities with the extension reaction (r =
      0.652 for M1, r = 0.813 for M2, P < 0.01). It became clear that the subjects with
      shorter reaction times inhibited their reflex activities of the flexor,
      particularly the M2 component which prevents the extension movement, to a greater
      degree than the subjects with longer reaction times. Therefore, our results
      suggest that the degree of M2 modulation directly reflects the individual motor
      control required to perform quick movements.

PMID- 9284239
TI  - Fatigue effects on body balance.
AB  - Body sway variables (sway area and sway path) were recorded by a dynamometric
      platform in 13 young subjects, standing quiet with feet together, with eyes open
      (EO) and eyes closed (EC), prior to and following two types of physical exercise
      (treadmill walking and cycle ergometer pedalling). Each exercise was performed
      under both fatiguing (above anaerobic threshold) and non-fatiguing conditions.
      Following fatiguing treadmill exercise, we observed a significant increase in
      body sway with respect to pre-exercise values. The increase was present under
      both visual conditions, affected both sway area and sway path and lasted until
      about 15 min from the end of the exercise. The Romberg quotient (the ratio of
      EC/EO of sway area, or sway path) significantly increased after the fatiguing
      exercise with respect to the non-fatiguing exercise. The mean position of the
      centre of foot pressure (CFP) was unchanged after the exercise. Fatigue induced
      an increase in the median frequency of oscillation of the centre of foot
      pressure, independent of the amplitude of sway. Non-fatiguing treadmill exercise
      induced no significant changes in sway or in its frequency content. Following
      fatiguing cycle ergometer exercise, a negligible increase or a decrease (under
      eyes closed condition) in body sway were observed. Non-fatiguing cycling exercise
      induced no significant changes or a decrease in sway. Control experiments showed
      that simple repetition of successive stance trials (without intercalated
      exercise) was able by itself to induce a decrease in sway. By taking this effect
      into account, both types of cycling exercises revealed a mild capacity to
      increase sway. We concluded that body sway increased after strenuous physical
      exercise, but was little affected by exercise performed below the estimated
      anaerobic threshold. The effects of fatigue on sway were short-lasting and of
      moderate extent, and therefore were not liable to seriously threaten body
      equilibrium.

PMID- 9284240
TI  - Conduction block and segmental velocities in carpal tunnel syndrome.
AB  - In carpal tunnel syndrome (CTS) standard measurement of median distal motor
      latency and sensory conduction does not distinguish whether low amplitude
      responses are due to axonal degeneration or demyelination. In 88 control and 294
      CTS hands we recorded amplitude and duration of compound muscle action potential
      (CMAP) and of antidromic sensory nerve action potential (SNAP) after palm and
      wrist stimulation to determine wrist to palm amplitude, duration ratios and
      segmental conduction velocities. In 16% of CTS hands there was an abnormal
      amplitude reduction without increased duration of CMAP or SNAP from wrist
      stimulation indicating partial conduction block. In 148 hands distal motor
      latency to abductor pollicis brevis and/or sensory conduction to digit 2 were
      abnormal. In the remaining 146 hands wrist to palm motor conduction was less than
      35 m/s in 22.6% and wrist to palm sensory conduction was less than 45 m/s in 13%.
      At least one segmental conduction was abnormal in 27% of hands. Segmental studies
      allow the discrimination between conduction block and axonal degeneration,
      increase diagnostic yield in CTS, and might be useful in addressing treatment and
      predicting outcome.

PMID- 9284241
TI  - Functional properties of motor units in motor neuron diseases and neuropathies.
AB  - The relationship between the size of single motor unit (MU) action potentials and
      their twitch properties was estimated in patients with spinal muscular atrophy
      (SMA, n = 5) and amyotrophic lateral sclerosis (ALS, n = 10), as well as in
      patients with peripheral nerve lesions (PNL, n = 9). The data obtained from these
      groups were compared to normal controls (n = 8). In controls, the single MU
      twitch force was highly correlated to the corresponding EMG potential size in
      terms of macro EMG area. An enlargement of MUs, due to collateral sprouting and
      reflected by increased potential size and twitch force, was found in regenerating
      PNL and in slowly progressing SMA. Both parameters were highly correlated which
      indicates a high functional quality of compensating mechanisms. However, in
      rapidly progressing forms of amyotrophic lateral sclerosis (ALS) this correlation
      is poor and reflects a disturbance of the contractile system. Contraction times
      and half relaxation times were not correlated in the different groups.

PMID- 9284243
TI  - Monte Carlo calculation of dose rate distributions around 192Ir wires.
AB  - Monte Carlo calculations of absolute dose rate in liquid water are presented in
      the form of away-along tables for 1 and 5 cm 192Ir wires of 0.3 mm diameter.
      Simulated absolute dose rate values can be used as benchmark data to verify the
      calculation results of treatment planning systems or directly as input data for
      treatment planning. Best fit value of attenuation coefficient suitable for use in
      Sievert-integrals-type calculations has been derived based on Monte Carlo
      calculation results. For the treatment planning systems that are based on TG43
      formalism we have also calculated the required dosimetry parameters.

PMID- 9284242
TI  - Quality assurance for dynamic multileaf collimator modulated fields using a fast
      beam imaging system.
AB  - A quality assurance procedure was developed for x-ray beam intensity modulated
      conformal radiotherapy (IMCRT) using dynamic multileaf collimators (MLC). The
      procedure verifies a prescribed intensity modulated x-ray beam pattern in the
      beam eye's view (BEV) before the treatment procedure is applied to a patient. It
      verifies that (a) the leaf sequencing computer files were transferred correctly
      to the linac control computer; (b) the treatment can be correctly executed
      without machine faults. A fast beam imaging system (BIS) consisting of a Gd2O2S
      scintillation screen, a charge-coupled device (CCD) camera, and a portable
      personal computer (Wellhofer Dosimetrie, Schwarzenbruck, Germany) was
      commissioned for this purpose. Measurements for the BIS performance are presented
      in this work. Reference images were derived from MLC leaf sequencing files that
      were used to drive a dynamic MLC system (Varian Oncology Systems, Palo Alto, CA).
      A correlation method was developed to compare the BIS measurements with the
      calculated reference images. A correlation coefficient calculated using 26
      correct intensity modulated fields was shown to be a reliable threshold to
      identify inaccurate treatment delivery files. The study has demonstrated the
      feasibility of using the BIS and the correlation method to carry out on-line
      quality assurance tasks for IMCRT treatment fields in the BEV.

PMID- 9284244
TI  - A method for more efficient source localization of interstitial implants with
      biplane radiographs.
AB  - The conventional method for source localization in an interstitial ribbon implant
      by means of biplane radiographs can be difficult, especially when a large number
      of seeds are involved. We present a new algorithm for more efficient source
      localization with the same conventional biplane radiographs. The method does not
      require a one-to-one source correspondence between two radiographs. The user
      needs only to digitize several points, following the shape of each ribbon from
      both films. The points that are digitized do not need to be the location of the
      seeds, and they do not have to correspond to the same points on both films. The
      algorithm uses the multidimensional minimization method to reconstruct the three
      dimensional locus of the ribbon. The location of each seed is then determined by
      its pathlength relative to the corresponding starting point. We have used phantom
      experiments and clinical cases to test the reliability of the algorithm. The
      results show that the errors in the determination of seed locations are less than
      2 mm, and the efficiency in source digitization for data entry can be increased
      by a factor up to 5.

PMID- 9284245
TI  - A depth-dose measuring device using a multichannel scintillating fiber array for
      electron beam therapy.
AB  - The development of a new depth-dose measuring device for electron beam therapy is
      described. The device employs plastic scintillating fiber detectors inserted in a
      polymethylmethacrylate (PMMA) phantom in line along an incident electron beam.
      Output photons from a fiber, the number of which is proportional to the absorbed
      dose at each depth of the phantom, were converted to an electric signal with a
      photodiode. Each signal from the photodiode was transmitted to a personal
      computer through a multichannel analog-digital converter, and was processed to
      draw a depth-dose curve on the computer display. A depth-dose curve could be
      obtained in a measuring time of 5 s for each incident electron beam with an
      energy range between 4 and 21 MeV. The mean electron energies estimated using the
      curves and the depth-scaling factor for PMMA were consistent with those obtained
      from conventional depth-dose measurements using an ion chamber and a water
      phantom. The newly developed system, being simple and not time consuming, could
      be used routinely for quality assurance purposes in electron beam therapy.

PMID- 9284246
TI  - The elemental composition of tumors: kerma data for neutrons.
AB  - The elemental composition of a variety of tumor samples, including squamous cell
      lung carcinoma, sarcoma, adenoid cystic carcinoma, melanoma, and rectal carcinoma
      have been measured by combustion analysis. Hydrogen, carbon, nitrogen, and oxygen
      content have been determined. Using the elemental neutron kerma data published in
      ICRU Report #46 the neutron kerma factors for the various tumor samples have been
      calculated in the energy range 11 eV to 29 MeV. The average neutron kerma values
      for all tumor samples are approximately 6%-7% lower than those for average soft
      tissue in the energy range of interest in fast neutron therapy (energies > 1
      MeV).

PMID- 9284247
TI  - The use of the linear-quadratic model in clinical radiation oncology can be
      defended on the basis of empirical evidence and theoretical argument.

PMID- 9284248
TI  - Uncertainty of calibrations at the accredited dosimetry calibration laboratories.
AB  - The American Association of Physicists in Medicine, through a subcommittee
      (formerly Task Group 3) of the Radiation Therapy Committee, has accredited five
      laboratories to perform calibrations of instruments used to calibrate therapeutic
      radiation beams. The role of the accredited dosimetry calibration laboratories
      (ADCLs) is to transfer a calibration factor from an instrument calibrated by the
      National Institute of Standards and Technology (NIST) to a customer's instrument.
      It is of importance to the subcommittee, to physicists using the services of the
      ADCLs, and to the ADCLs themselves, to know the uncertainty of instrument
      calibrations. The calibration uncertainty has been analyzed by asking the
      laboratories to provide information about their calibration procedures. Estimates
      of uncertainty by two procedures were requested: Type A are uncertainties derived
      as the standard deviations of repeated measurements, while type B are estimates
      of uncertainties obtained by other methods, again expressed as standard
      deviations. Data have been received describing the uncertainty of each parameter
      involved in calibrations, including those associated with measurements of charge,
      exposure time, and air density, among others. These figures were combined with
      the uncertainty of NIST calibrations, to arrive at an overall uncertainty which
      is expressed at the two-standard deviation level. For cable-connected instruments
      in gamma-ray and x-ray beams of HVL > 1 mm Al, the figure has an upper bound of
      approximately 1.2%.

PMID- 9284249
TI  - Probability-based structural parameters from three-dimensional nuclear magnetic
      resonance images as predictors of trabecular bone strength.
AB  - The mechanical competence of trabecular bone is a function of its apparent
      density and three-dimensional (3D) distribution. Three-dimensional structure is
      typically inferred from histomorphometry and stereology on a limited number of
      two-dimensional anatomic sections. In this work 3D nuclear magnetic resonance
      (NMR) images of anisotropic trabecular bone from the distal radius were analyzed
      in terms of a series of new structural parameters which are obtainable at
      relatively crude resolution, i.e., in the presence of substantial partial volume
      blurring. Unlike typical feature extraction techniques requiring image
      segmentation, the method relies on spatial autocorrelation analysis, which is
      based on the probability of finding bone at specified locations. The structural
      parameters were measured from high-resolution images (78x78x78 microm3 voxels) of
      23 trabecular bone specimens from the distal radius. Maximum-likelihood bone
      volume fractions (BVF) were calculated for each voxel and a resolution achievable
      in vivo (156x156x391 microm3 voxels) was simulated by averaging BVF's from
      neighboring voxels. The parameters derived from the low-resolution images were
      found to account for 91% of the variation in Young's modulus. The results suggest
      that noninvasive assessment of the mechanical competence of trabecular bone in
      osteoporotic patients may be feasible.

PMID- 9284250
TI  - Comparison of exposure standards in the mammography x-ray region.
AB  - Direct comparisons of the National Institute of Standards and Technology's (NIST)
      Ritz 20 kV to 100 kV standard free-air ionization chamber and a portable variable
      length free-air ionization chamber designed by the University of Wisconsin
      Madison Accredited Dosimetry Calibration Laboratory (UW-ADCL) were made on NISTs
      low-energy tungsten x-ray range. As a result of this direct comparison, NIST has
      established a UW-ADCL designed chamber, the Attix chamber, as the national
      standard chamber for the mammography energy x-ray range. The Ritz standard
      chamber and the Attix standard chamber have been extensively compared using the
      new molybdenum and rhodium beam qualities. The results indicate that exposure
      measurements in the mammography energy x-ray region with the two free-air
      chambers can be made with a discrepancy of less than 0.35%.

PMID- 9284251
TI  - Computer analysis of mammography phantom images (CAMPI): an application to the
      measurement of microcalcification image quality of directly acquired digital
      images.
AB  - The purpose of this investigation was to apply the recently developed CAMPI
      (computer analysis of mammography phantom images) method to a Fischer Mammotest
      Stereotactic Digital Biopsy machine. Another aim was to further elucidate the
      nature of the empirically introduced CAMPI measures. Images of an American
      College of Radiology (ACR) accreditation phantom centered on the largest two
      speck groups were obtained on this machine under a variety of x-ray conditions.
      An additional measure, alternative SNR (ASNR) is introduced which is
      complementary to the SNR measure. Analyses of the Mammotest images revealed that
      the mAs and kVp dependencies of the CAMPI measures could be understood from basic
      imaging physics principles. It is shown that: (1) the measures reflect the
      expected linearity of the digital detector and Poisson photon statistics; (2)
      under automatic exposure control (AEC) conditions the signal (SIG) measure is
      proportional to subject contrast; and (3) under AEC conditions the noise (NOI)
      measure is proportional to the square root of the average absorbed photon energy.
      Correspondence with basic imaging physics principles shows that the measures are
      significantly free of artifacts. Precision of the CAMPI measures exceeds that of
      human observers by orders of magnitude. CAMPI measures are expected to be more
      relevant to clinical mammography than Fourier metrics as the measurements are
      done on objects of arbitrary shape and size that were designed by the
      manufacturer to resemble various detection tasks in mammography. It is concluded
      that CAMPI can perform objective and highly precise evaluations of phantom image
      quality in mammography. It could be used as a sophisticated quality control tool,
      as a replacement for the current ACR/MQSA phantom evaluation program, and to
      evaluate the rapidly evolving digital mammography technology.

PMID- 9284252
TI  - X-ray imaging with amorphous selenium: theoretical feasibility of the liquid
      crystal light valve for radiography.
AB  - A novel radiographic imaging system based on a liquid crystal light valve is
      described. A liquid crystal light valve is a photon addressed spatial light
      modulator that consists of a high resolution, solid-state electrostatic detector
      (photoconductor) and an electro-optic light modulator (liquid crystal cell)
      physically coupled in a sandwich structure. We propose a light valve with a
      thick, x-ray sensitive photoconductive layer and call the system under study the
      x-ray light valve (XLV). The image formation in the XLV is based on x-ray
      exposure controlled modulation of light from an external source; the XLV is
      essentially an x-ray image intensifier that allows the image brightness to be
      adjusted independently from the x-ray exposure. Thus the XLV may be coupled to an
      optical imager, such as a charge coupled device (CCD), for image digitization
      without a secondary quantum sink. A model of the XLV operation is developed to
      investigate its sensitivity, speed, noise, and resolution. The imaging properties
      of the XLV are found to be time dependent, which leads to an unusual transmission
      versus exposure characteristic. The feasibility of clinical use of the XLV based
      on amorphous selenium (a-Se) photoconductor and a twisted nematic liquid crystal
      cell is analyzed, and the device is shown to be adaptable to a variety of
      radiographic imaging tasks.

PMID- 9284253
TI  - Improvement of signal-to-noise and contrast-to-noise ratios in dual-screen
      computed radiography.
AB  - A dual-screen computed radiography (CR) technique has been developed to improve
      and optimize the overall image signal-to-noise ratio (SNR) and contrast-to-noise
      ratio (CNR). With this technique, two CR screens are exposed together and
      separately scanned to form a front and a back image. These two images are then
      superimposed to form an image of improved SNR and CNR. A mathematical model has
      been derived to describe the improvement and optimization of the SNR and CNR.
      Based on this model, the front and back images should be weighted in proportion
      to their SNR squared to optimize the SNR of the composite image. Imaging
      experiments have been conducted to verify the theoretical model under
      mammographic and chest imaging conditions. The results largely agree with the
      theoretical predictions. It has also been found that optimization of the SNR
      results in nearly optimal CNR and vice versa. For mammographic imaging, a 14%-22%
      improvement in the SNR and a 13%-19% improvement in the CNR have been
      demonstrated. For chest imaging, a 31%-36% improvement in the SNR and a 28%-30%
      improvement in the CNR has been demonstrated.

PMID- 9284255
TI  - Effective dose and energy imparted in diagnostic radiology.
AB  - The patient effective dose, E, is an indicator of the stochastic radiation risk
      associated with radiographic or fluoroscopic x-ray examinations. Determining
      effective doses for radiologic examinations by measurement or calculation is
      generally very difficult. By contrast, the energy imparted, epsilon, to the
      patient may be obtained from the x-ray exposure-area product incident on the
      patient. As energy imparted is approximately proportional to the effective dose
      for any given x-ray radiographic view, the availability of E/epsilon ratios for
      common radiographic projections provides a convenient way for estimating
      effective doses. Ratios of E/epsilon were obtained for 68 projections using E and
      epsilon values obtained from published dosimetry data computed using Monte Carlo
      techniques on an adult anthropomorphic phantom. The average E/epsilon ratio for
      the 68 projections in adults was 17.8+/-1.4 mSv/J, whereas uniform whole body
      irradiation corresponds to 14.1 mSv/J. The major determinant of E/epsilon ratios
      was the projection employed (the body region irradiated and x-ray beam
      orientation), whereas the tube potential and beam filtration were of secondary
      importance. Adult E/epsilon ratios may also be used to obtain effective doses to
      pediatric patients undergoing x-ray examinations by application of a correction
      factor based on the patient mass.

PMID- 9284256
TI  - Comment on "Dosimetric characteristics of an improved radiochromic film" [Med.
      Phys. 23, 1883-1888 (1996)] and on "Qualitative evaluation of radiochromic film
      response for two-dimensional dosimetry" [Med. Phys. 24, 223-231 (1997)].

PMID- 9284254
TI  - The skeletal calcium/phosphorus ratio: a new in vivo method of determination.
AB  - We describe a new method for assessing the Ca/P ratio of bone in vivo using gamma
      ray photon absorptiometry. The theoretical approach of the method and the
      estimation of the variance are presented. Two radiation sources, Gd-153 (100
      keV), and I-125 (27.5 keV), and a germanium detector were used to determine this
      ratio. Measurements were made on bone phantoms with different Ca/P ratios; also,
      the ratio was measured on lamb and sheep tibias, rabbit tibias, and human
      fingers. Since the accuracy of the method is affected by the amount of fat and
      collagen in the measurement field, the effect of collagen and fat on the
      measurements also was investigated. In all cases, the precision of the method,
      expressed as the coefficient of variation (CV): 100x standard deviation/mean, was
      near to the theoretical one, ranging from 1.8% to 3.2%. For human fingers, the CV
      was 3.2%, a value near to the theoretical 2.9% with a dose to the skin ranging
      from 0.044 to 0.066 mGy, depending on the width of the finger.

PMID- 9284257
TI  - Comment on "Monte Carlo simulation of Cf-252 dose distribution brachytherapy"
      [Med. Phys. 23, 707-711 (1996)].

PMID- 9284258
TI  - Comment on "Reporting and analyzing dose distributions: a concept of equivalent
      uniform dose" [Med. Phys. 24, 103-109 (1997)].

PMID- 9284259
TI  - Comment on "Point/Counterpoint: The use of the linear-quadratic model in clinical
      radiation oncology can be defended on the basis of empirical evidence and
      theoretical argument" [Med. Phys. 24, 1245-1248 (1997)].

PMID- 9284260
TI  - Potential radiation hazard associated with the unprotective use of mini C-arm
      fluoroscopy systems.

PMID- 9284261
TI  - The biology of pneumococcal infection.
AB  - For 100 y, the study of the molecular mechanism of pneumococcal infection has
      richly rewarded biomedical science and pediatrics. More recently, a framework has
      emerged for how the pathogen engineers colonization, invasion of the lung and
      bloodstream, and finally, entry into the brain. This trafficking is then followed
      by a separate set of events to generate the symptoms of disease. Understanding
      the ligand receptor interactions that dictate these events has suggested new
      concepts for how to control the course of an infectious process and improve the
      morbidity and mortality of encounters with this prevalent pathogen of children.

PMID- 9284262
TI  - Fc gammaRIIa polymorphism in human immunodeficiency virus-infected children with
      invasive pneumococcal disease.
AB  - Invasive pneumococcal disease (IPD) occurs frequently in HIV-infected children
      and adults. Defects in complement function, opsonic capsular antibodies, and Fc
      receptor antibody-mediated phagocytosis could contribute to impaired host defense
      against Streptococcus pneumoniae. The objective of this study was to define the
      distribution of the three Fc gammaRIIa genotypes in HIV+ children, including
      those with IPD. Forty-eight HIV+ Hispanic children, including eight with IPD,
      followed at Bronx-Lebanon Hospital Center, Bronx, New York, nine HIV+ adults with
      IPD, and 56 HIV- Hispanic control subjects were studied. The children and adults
      were identified retrospectively except for one child who developed IPD during the
      study. Fc gammaRIIa genotypes were determined by PCR amplification of the Fc
      gammaRIIa locus from genomic DNA samples and hybridization of the PCR products
      with allele-specific oligonucleotides. Naturally occurring serum antibodies
      reactive with four pneumococcal polysaccharide serotypes were determined by ELISA
      in seven of eight children with IPD. There were no statistical differences in Fc
      gammaRIIa genotypes between HIV+ children with and without IPD, HIV+ adults with
      IPD, or HIV- Hispanics. The predominant IgG subclass of pneumococcal
      polysaccharide binding antibodies in the seven HIV+ children with IPD studied was
      IgG1. The distribution of Fc gammaRIIa genotypes in HIV+ children with and
      without IPD is similar to that of the normal Hispanic population. The prospect of
      passive immunotherapy with specific anticapsular antibodies might be a promising
      alternative for the treatment and/or prevention of IPD in HIV+ children and other
      immunodeficient groups.

PMID- 9284263
TI  - Loss of circulating hepatitis C virus in children who developed a persistent
      carrier state after mother-to-baby transmission.
AB  - Of the 15 babies born to mothers infected with hepatitis C virus (HCV) and
      followed since birth, three developed HCV RNA in their serum. HCV RNA disappeared
      in two infants within 2 mo, but it persisted in the remaining infant. Mother-to
      baby transmission was diagnosed retrospectively in an additional eight children
      aged 0.8-13.6 y. The eight children were followed for 1.4-5.0 y (mean +/- SD: 3.2
      +/- 1.3 y) until they were 3.3-16.7 y old (8.5 +/- 4.3 y). Serum HCV RNA
      disappeared and antibodies to HCV decreased in the titer in two of the children
      when they were 3 y old. The spontaneous loss of serum HCV RNA was not observed in
      any of the other 14 children with posttransfusion infection who were followed for
      2.6-6.1 y (4.0 +/- 1.1 y), until 3-22 y from the time they received transfusions
      and when they were 8.4-22.8 y old (15.4 +/- 4.1 y). These results indicate that
      the vertical transmission of HCV is rare, and some children can resolve the
      infection after a few years, whereas the infection persists in children who are
      infected by transfusion.

PMID- 9284265
TI  - Left ventricular systolic function, arterial elastance, and ventricular-vascular
      coupling: a developmental study in piglets.
AB  - Circulatory changes occur during perinatal life that increase cardiac output and
      left ventricular contractile reserve. To examine postnatal changes in left
      ventricular systolic function and ventricular-vascular coupling, piglets
      underwent cardiac catheterization at 1, 2, 4, and 6 wk of age. We measured end
      systolic elastance (Ees), preload-recruitable stroke work, dP/dt(max), the
      dP/dt(max) end-diastolic volume relation, cardiac index, heart rate, arterial
      elastance (Ea), and the ratio Ea/Ees, at rest, during isoproterenol infusions
      (0.05-1.0 microg/kg/min), and after propranolol (1 mg/kg i.v.). Resting heart
      rate and cardiac index decreased between 1 and 6 wk. In 1 wk olds, resting Ees
      was at maximum and was unchanged during isoproterenol infusion; isoproterenol
      increased other contractility indices. Two, 4, and 6 wk olds demonstrated reserve
      using all contractility indices. Contractile efficiency was not different between
      ages. In 1 wk olds, Ea decreased during isoproterenol infusion; isoproterenol did
      not change Ea at 6 wk. Ea/Ees was higher at rest at 6 wk than at 1 wk, and fell
      significantly on isoproterenol; isoproterenol did not change Ea/Ees at 1 wk. With
      beta-adrenergic stimulation, 1 wk olds increased cardiac index by increasing
      heart rate and decreasing afterload, 6 wk olds increased cardiac index by
      increasing heart rate and contractility; no change in contractile efficiency was
      found in either group. In summary, contractile reserve is limited at 1 wk when
      measured by Ees, but other indices demonstrated reserve. Indexed Ea falls in
      response to beta-adrenergic stimulation in all ages but 6 wk. Ventricular
      vascular coupling is optimized at 1 wk even under baseline conditions.

PMID- 9284264
TI  - Association of toxic shock syndrome toxin-secreting and exfoliative toxin
      secreting Staphylococcus aureus with Kawasaki syndrome complicated by coronary
      artery disease.
AB  - Kawasaki syndrome (KS) has been reported to be associated with selective
      expansion of Vbeta2+ T cells and either staphylococcal toxic shock syndrome toxin
      1 or streptococcal pyrogenic exotoxin C in uncomplicated cases. However, there
      have been no previous studies on the role of superantigens in KS associated with
      coronary artery disease, the major complication of this illness. The present
      study characterized bacteria isolated from three acute KS patients who developed
      coronary artery disease. Staphylococcus aureus secreting either TSST-1 (n = 3) or
      exfoliative toxin A (n = 1), both known to stimulate expansion of Vbeta2+ T
      cells, were isolated from all three patients. The percent Vbeta2+ T cells was
      determined in three patients with coronary artery disease. On presentation, one
      patient demonstrated reduction, whereas the other two showed expansion, of
      Vbeta2+ T cells. Repeat analyses of the latter two children showed their percent
      Vbeta2+ T cells to decrease toward normal. These observations suggest that
      coronary artery disease in KS may result from superantigenic stimulation of
      Vbeta2+ T cells. This is also the first demonstration of an association of
      staphylococcal exfoliative toxin with acute KS. The observation that three
      different bacterial toxins associated with KS are potent activators of Vbeta2+ T
      cells suggests an important role for this T cell subset in the pathogenesis of
      this autoimmune disease.

PMID- 9284266
TI  - Thermal entrainment of heart rate in the preterm infant.
AB  - Using spectral analysis we have studied changes in the heart rate during periodic
      thermal stimulation of one foot of infants during quiet sleep. Twenty-two
      appropriately grown preterm infants were studied in the first 15 d after birth to
      quantify responses in comparison with previously reported term infants. Babies
      were stimulated at 0.05, 0.10, and 0.15 Hz. Spectral power was calculated at the
      stimulus frequency +/-0.01 Hz and +/-0.02 Hz and over the low frequency range
      0.03 Hz to 0.17 Hz. The data show that 1) there is an increase in power around
      the frequency of stimulation for each frequency studied (p < 0.002); and 2) there
      is an increase in the ratio of local to low frequency power at 0.05 Hz (p =
      0.002) and 0.10 Hz (p = 0.001), but not at 0.15 Hz (p = 0.109). These data
      confirm the concept of entrainment in the appropriately grown preterm infant but
      demonstrate that it occurs over a wider frequency range than previously reported.
      The wider range is the same as that of the term infant, although there are
      differences in the patterns of entrainment between the two groups. Further work
      is required to map out the maturation of the autonomic nervous system in both the
      term and the preterm infant with respect to the low frequency components of the
      heart rate variability power spectrum.

PMID- 9284267
TI  - Caffeine-induced contractions in developing rabbit heart.
AB  - Mature myocardium utilizes calcium released by the sarcoplasmic reticulum (SR)
      for cell contraction. Transient exposure of mature myocytes to caffeine is known
      to directly trigger Ca2+ release from the SR. In contrast, neonatal rabbit heart
      cells rely on transsarcolemmal Ca2+ influx for tension generation. SR function is
      decreased in immature heart and appears to play a minimal role as a calcium
      source. Accordingly, we hypothesized that neonatal rabbit myocytes would not
      respond to a caffeine pulse. Isolated neonatal and adult myocytes were paced to
      load the SR with calcium and then exposed to a 1-s pulse of 10 mM caffeine. As
      previously described, adult myocytes exhibited a brisk contraction in response to
      caffeine. Unexpectedly, neonatal myocytes also exhibited a similar, brisk
      response. These caffeine-induced contractions were not dependent on extracellular
      Ca2+ but were dependent upon the loading of SR Ca2+ stores. When SR Ca2+ stores
      were depleted by exposure to caffeine, mature myocytes exhibited only small, slow
      contractions in response to electrical field stimulation. Replenishing the SR
      Ca2+ stores resulted in normal, brisk contractions. In contrast, electrically
      stimulated contractions in immature myocytes were largely unaffected by caffeine
      induced SR depletion. Thus, although neonatal myocytes are capable of loading and
      releasing calcium from the SR, such SR calcium release is not normally required
      for contraction in the developing heart. The minor role of SR Ca2+ release in
      immature rabbit heart may not result from immaturity of the SR, but rather from
      an inadequate mechanism to trigger SR calcium release.

PMID- 9284268
TI  - Changes in mean chorioallantoic artery blood flow and heart rate produced by
      hypoxia in the developing chick embryo.
AB  - Hypoxia in the mammalian fetus produces cardiovascular changes, such as
      bradycardia, systemic hypertension, and changes in heart rate variability. This
      response was studied in 140 chick embryos ranging from stage 34 to stage 42 (d 9
      16 of the 21-d incubation), by measuring the changes in mean chorioallantoic
      artery blood flow (CABF) and heart rate for 5 min in two levels of hypoxia (group
      1; n = 90; 100% N2) or (group 2; n = 50; 5% O2). Eggs were opened at the air cell
      and placed in a small plexiglass holder, which had a continuous gas flow of an
      O2/N2 mixture (5 L/min), at 38 degrees C and 60% humidity. The chorioallantoic
      artery was placed in the lumen of a flow probe to measure mean CABF, heart rate,
      peak flow, and blood flow acceleration. After baseline measurements, the gas
      mixture was changed to 100% N2 or 5% O2 in N2 for 5 min. Mean CABF and heart rate
      decreased significantly in both groups (Wilcoxon paired sample test, p < 0.05).
      This response was more pronounced with the development of the chick embryo.
      Chorioallantoic artery peak flow (mL/min) and CABF acceleration (mL/s2) increased
      with incubation time and decreased during periods of hypoxia. During recovery,
      heart rate returned to baseline levels, whereas mean CABF showed an overshoot.
      The initial decrease in mean CABF and heart rate was similar in both groups. The
      cardiovascular response to hypoxia in the chick embryo is similar to the response
      in the mammalian fetus. The more pronounced response in the more developed chick
      embryo may represent a maturation of cardiovascular control.

PMID- 9284269
TI  - Perinatal regulation of the cerebral circulation: role of nitric oxide and
      prostaglandins.
AB  - Nitric oxide (NO) influences cerebral vascular tone both in the normal fetus and
      in the hypoxemic fetus, but during postnatal life this regulating role of NO
      seems less prominent. It is therefore possible that under conditions when
      arterial oxygen content is at postnatal levels NO exerts no action on smooth
      muscle. We therefore examined the impact of NO on cerebral blood flow and
      vascular resistance in five near-term lamb fetuses during intrauterine
      ventilation and oxygenation. Four additional fetuses were pretreated with
      indomethacin to investigate a possible additional regulatory role of
      prostaglandins on cerebral vascular resistance. Cerebral blood flow (Qbrain) was
      measured using radionuclide-labeled microspheres. A tracheal tube was inserted to
      ventilate the fetus. After recovery, Qbrain and resistance in the cerebral
      vascular bed (Rcer) were measured during the following subsequent conditions:
      before and after increasing fetal arterial O2 content by ventilation with air,
      after inhibition of NO production with N(omega)-nitro-L-arginine during and after
      cessation of ventilation, and finally after infusion of L-arginine to increase
      nitric oxide production. Ventilation decreased Qbrain (95 +/- 18 to 47 +/- 15
      mL/100 g/min) and increased Rcer. N(omega)-Nitro-L-arginine did not alter Qbrain
      (52 +/- 13 mL/100 g/min) or Rcer during ventilation and oxygenation, indicating
      no modulating role of NO during higher arterial oxygen content. On cessation of
      ventilation, PO2 returned to fetal levels and Qbrain increased significantly, but
      did not return to baseline fetal values (83 +/- 7 mL/min). Infusion of L-arginine
      increased Qbrain to baseline fetal levels (116 +/- 30 mL/min). However,
      indomethacin pretreatment prevented the rise in cerebral blood flow after
      cessation of ventilation and after additional L-arginine infusion (Qbrain 53 +/-
      20 and 52 +/- 4 mL/100 g/min. respectively). These studies indicate that, during
      postnatal levels of arterial oxygen content, NO does not exert an action on
      smooth muscle cells of the cerebral resistance vessels as it does at lower
      arterial (fetal) oxygen content. They further show that prostaglandins are
      important in facilitating the full expression of NO-induced vasodilation.

PMID- 9284271
TI  - Regional cerebral glucose utilization in immature fetal guinea pigs during
      maternal isocapnic hypoxemia.
AB  - Recent studies in immature fetal animals demonstrated only a slight or variable
      increase in the cerebral glycolytic rate during moderate isocapnic hypoxemia.
      However, the methods used in those studies did not allow for detection of small
      differences or of regional redistributions of the cerebral glycolytic rate.
      Hence, a global increase or a regional redistribution of the cerebral glycolytic
      rate during hypoxemia accompanied by a severe increase in tissue lactate
      concentration in a few brain areas may have been overlooked in these studies.
      Because these pathophysiologic mechanisms seem to considerably exacerbate
      neuronal cell damage due to hypoxic/ischemic insults, we were keen to clarify
      this point. We, therefore, applied the 2-deoxyglucose method to fetal guinea pigs
      in utero and measured total and regional cerebral glucose utilization in fetuses
      of this species at 0.75 of gestation during maternal isocapnic hypoxemia. At 0.75
      of gestation guinea pig dams were chronically catheterized. Control groups were
      exposed to room air, whereas study groups were exposed to a hypoxic atmosphere
      (10% oxygen, 2% carbon dioxide, and 88% nitrogen). To measure total and regional
      cerebral glucose utilization during normoxemia and isocapnic hypoxemia, we
      injected i.v. 100 microCi of 2-[3H]deoxyglucose into the dams. Total and regional
      cerebral glucose utilization were determined from the steady-state clearance of 2
      deoxyglucose between the maternal arterial plasma and the fetal brain, the
      glucose concentration in the maternal arterial plasma, and the "lumped constant."
      During isocapnic hypoxemia, total fetal cerebral glucose utilization was not
      significantly higher than that previously measured during normoxemia (8 +/- 0.8
      versus 8 +/- 1.0 micromol/100 g/min). Furthermore, no redistribution of cerebral
      glucose utilization could be detected. We conclude that moderate isocapnic
      hypoxemia in the immature fetal brain does not lead to any significant increase
      or redistribution of glucose utilization or to any major lactate accumulation.
      This may be related to the low cerebral metabolic demands of brain tissue at this
      stage of development. Whether this is the main reason for the known resistance of
      the immature fetal brain toward ischemic neuronal cell damage remains to be
      established.

PMID- 9284270
TI  - The effects of intraventricular/periventricular blood on cerebral 3',5'-cyclic
      adenosine monophosphate concentration and cerebrovascular reactivity in newborn
      pigs.
AB  - This study investigated the effects of intraventricular/periventricular blood on
      cerebral cAMP production and cortical cerebrovascular reactivity. Under halothane
      and N2O anesthesia, 3 mL of either autologous blood or artificial cerebrospinal
      fluid (CSF) were injected into the left caudate nucleus; volume was adequate to
      result in extrusion of fluid or blood into the lateral ventricles of 1-2-d-old
      piglets. Twenty-four hours later, a closed cranial window was implanted over the
      left parietal cortex. Pial arteriolar responses to vasodilator and
      vasoconstrictor stimuli were monitored. Before the application of vasoactive
      agents, cortical periarachioid CSF was collected for cAMP measurement. Pial
      arteriolar responses to topical application of endothelin-1 (10(-9) and 10(-8) M)
      and to leukotriene C4 (10(-10) and 10(-9) M) were similar between the two groups.
      However, pial arteriolar responses to topical application of cAMP-mediated
      vasodilators, prostaglandin E2 (10(-6) and 10(-5) M), and histamine (10(-6) and
      10(-5) M), respectively, were markedly reduced in the blood group when compared
      with the artificial CSF (control) group. Mean CSF cAMP level in the blood group
      was significantly lower than the control group (199 +/- 31 versus 1092 +/- 238
      fmol/mL, p = 0.0006). We conclude that in newborn pigs
      intraventricular/periventricular blood results in a marked reduction of CSF cAMP
      concentration and attenuation of the cerebrovascular responses to cAMP-mediated
      vasodilators on the cortical surface remote from the site of blood or hematoma.

PMID- 9284272
TI  - ATP-dependent K+ channel activation in isolated normal and hypertensive newborn
      and adult porcine pulmonary vessels.
AB  - The role of an ATP-dependent K+ channel (K(ATP)+) relaxation in the porcine
      pulmonary vasculature from birth to adulthood was investigated in vitro using
      levcromakalim on isolated, prostaglandin F2alpha (30 microM)-precontracted
      conduit arteries (CA), resistance arteries (RA), and veins (PV). Vessels from
      neonatal pulmonary hypertensive piglets exposed to chronic hypobaric hypoxia
      (CHH, 51 kPa) for 3 d, either from birth or from 3 d of age were also studied.
      Levcromakalim relaxed all vessels in a concentration- and glibenclamide-sensitive
      manner. In normal CA, the maximal extent of relaxation and sensitivity (EC50)
      increased between birth and 17 d. Endothelium-removal increased EC50 at 17 d
      only. Indomethacin (10 microM), but not N(G)-monomethyl-L-arginine (L-NMMA) (30
      microM), inhibited relaxation in CA from newborn, 3-d-old, and adult animals. In
      RA, levcromakalim-induced relaxations did not change during development and
      endothelium-removal attenuated relaxations in 3-d-old but not in adult animals.
      At both ages in RA, L-NMMA attenuated relaxations and subsequent addition of L
      arginine (1 mM) restored them. In PV, maximal relaxation increased between birth
      and 6 d with no change of EC50. At all ages, relaxation was partially endothelium
      dependent and inhibited by L-NMMA (except in the newborn). Indomethacin only
      attenuated relaxations in veins from 6- and 17-d-old animals. CHH did not
      influence relaxant responses in CA and PV but decreased EC50 in RA. Thus K(ATP)+
      channel activation caused relaxation from birth onward in all vascular segments
      with varying endothelium dependence. CHH did not affect relaxation in the large
      vessels and up-regulated those in RA. These findings indicate a possible role for
      K(ATP)+ channels during normal adaptation and a potential therapeutic role in the
      management of pulmonary hypertensive newborn infants.

PMID- 9284274
TI  - Bioactivity of a 29-kilodalton insulin-like growth factor binding protein-3
      fragment present in excess in chronic renal failure serum.
AB  - Children with chronic renal failure (CRF) have normal or high serum levels of GH,
      IGF-I, and IGF-II. Despite this, the serum of CRF patients has low IGF
      bioactivity, which may contribute to CRF growth failure. Recent studies suggest
      that excess IGF binding proteins (IGFBPs) in the approximately 35-kD fractions of
      CRF serum contribute to this low IGF bioactivity. This report characterizes a 29
      kD form of IGFBP-3, IGFBP-3(29), which accumulates in the approximately 35-kD
      fractions of CRF serum and peritoneal dialysate. Deglycosylation and [125I]IGF
      ligand blot studies show that IGFBP-3(29) is a glycosylated IGFBP-3 fragment with
      low affinity for IGF peptides. Using an IGFBP-3 antibody column, IGFBP-3(29) was
      purified to homogeneity from the approximately 35-kD fractions of peritoneal
      dialysate from children with CRF. Compared with native IGFBP-3, pure IGFBP-3(29)
      has a 4-10-fold lower affinity for IGF-II and a 200-fold lower affinity for IGF
      I. Consistent with the binding data, IGFBP-3(29) inhibited IGF-II-stimulated
      thymidine incorporation in chondrosarcoma cells, but was a less potent inhibitor
      than native IGFBP-3; also, native IGFBP-3 clearly inhibited IGF-I-stimulated
      thymidine incorporation in chondrosarcoma cells and potentiated IGF-I-stimulated
      aminoisobutyric acid uptake in bovine fibroblasts, but higher concentrations of
      IGFBP-3(29) had no effect on these IGF-I actions. Thus, the 29-kD IGFBP-3 form
      that accumulates in CRF serum and extravascular spaces is an IGFBP-3 fragment
      that may modulate IGF-II, but not IGF-I, effects on target tissues. Whether IGFBP
      3(29) plays any role in the growth failure of children with CRF remains to be
      determined.

PMID- 9284273
TI  - The alpha subunit of the epithelial sodium channel in the mouse: developmental
      regulation of its expression.
AB  - Sodium reabsorption by the amiloride-sensitive sodium channel of epithelial cells
      plays a crucial role in the management of ionic composition and fluid volume in
      the body. In the respiratory system, sodium transport is involved in the
      clearance of pulmonary edema and of liquid secreted during fetal life at birth.
      We have cloned a partial cDNA of the alpha subunit of the mouse amiloride
      sensitive sodium channel (alpha mENaC). In the region of comparison, the mouse
      alpha subunit shows 92% identity at the DNA level and 95% identity at the amino
      acid level with the rat sequence. The kidneys, lungs, and distal colon are major
      sites of expression of a 3.5-kb alpha mENaC mRNA. During mouse development, alpha
      mENaC transcripts appear late during gestation (d 17.5) and are expressed
      continuously thereafter. In the distal colon, a short 1.2-kb mRNA deleted of the
      5' part of the transcript is detected during gestation and is replaced gradually
      by the mature 3.5-kb transcript after birth. Alpha mENaC and alpha1 Na+-K+-ATPase
      mRNAs have an expression profile that is modulated similarly during development
      for a given tissue. The expression of alpha mENaC transcripts increases
      transiently in the lungs at birth (2.5-fold), as for alpha1 Na+-K+-ATPase mRNAs
      (1.5-fold), suggesting that the expression of several components of the sodium
      transport system is modulated in the lungs at that time. In the kidney, there is
      no significant increase of alpha mENaC and alpha1 Na+-K+-ATPase mRNAs in
      newborns.

PMID- 9284275
TI  - Promoting meconium clearance from the lungs of the neonatal piglet with
      asymmetric high frequency oscillation.
AB  - To investigate the role of high frequency oscillation (HFO) in promoting meconium
      clearance from the airway, we used a commercially available ventilator configured
      with maximal expiratory flow exceeding inspiratory flow (asymmetric HFO or AHFO).
      We hypothesized that AHFO would move meconium in an expiratory direction (toward
      the ventilator). We first tested our hypothesis in vitro and, later, in vivo
      using the neonatal piglet. In vitro experiments using a Plexiglas airway
      confirmed meconium movement in an expiratory direction when bias ratio was > or =
      2. For in vivo experiments, each piglet received a 3 mL/kg intratracheal bolus of
      a 44 g/100 mL meconium mixture followed by 45 min of mechanical ventilation.
      Then, in part 1, the piglet was placed in a 15 degree head down tilt position and
      randomized to either AHFO [ratio of inspiratory time/expiratory time (I:E) of
      70:30] or HFO (I:E ratio of 30:70). After 30 min of either AHFO or HFO, the
      piglet was crossed over to the alternate strategy for an additional 30 min. For
      part 2, we maintained the piglet on either AHFO or HFO continuously for 4 h.
      Results demonstrate that, although there was a tendency for larger volumes of
      meconium to be aspirated from the airway during AHFO in part 1 experiments, there
      was no difference found in part 2. We also found no significant differences in
      blood gases or hemodynamic measurements between AHFO and HFO during the prolonged
      observation period in part 2 of our study. We conclude that AHFO is of no benefit
      in the treatment of meconium aspiration syndrome.

PMID- 9284276
TI  - Manual ventilation with a few large breaths at birth compromises the therapeutic
      effect of subsequent surfactant replacement in immature lambs.
AB  - The reason why some infants with respiratory distress syndrome fail to respond to
      surfactant, or respond only transiently, is incompletely understood. We
      hypothesized that resuscitation with large breaths at birth might damage the
      lungs and blunt the effect of surfactant. Five pairs of lamb siblings were
      delivered by cesarean section at 127-128 d of gestation. One lamb in each pair
      was randomly selected to receive six manual inflations of 35-40 mL/kg ("bagging")
      before the start of mechanical ventilation, a volume roughly corresponding to the
      inspiratory capacity of lamb lungs after prophylactic surfactant supplementation.
      Both siblings were given rescue porcine surfactant, 200 mg/kg, at 30 min of age.
      Blood gases and deflation pressure-volume (P-V) curves of the respiratory system
      were recorded until the lambs were killed at 4 h. The P-V curves became steeper
      after surfactant in the control group, but no such effect was seen in those
      subjected to bagging. At 4 h, inspiratory capacity and maximal deflation
      compliance were almost three times higher (p < 0.01) in the controls than in the
      bagged lambs. The latter were also more difficult to ventilate and tended to have
      less well expanded alveoli and more widespread lung injury in histologic
      sections. We conclude that a few inflations with volumes that are probably
      harmless in other circumstances might, when forced into the surfactant-deficient
      lung immediately at birth, compromise the effect of subsequent surfactant rescue
      treatment. Our findings challenge current neonatal resuscitation practice of
      rapidly establishing a normal lung volume by vigorous manual ventilation.

PMID- 9284278
TI  - Regulation of migrating motor complexes by motilin and pancreatic polypeptide in
      human infants.
AB  - In adults, migrating motor complexes (MMCs) appear to be partially under hormonal
      modulation by motilin and pancreatic polypeptide. Preterm infants do not exhibit
      MMCs until 32 wk of gestation. Although plasma concentrations of motilin are
      similar in infants and adults, it is not known if actual hormonal modulation of
      MMCs is present in infants. In the first study we assessed whether plasma
      concentrations of motilin and pancreatic polypeptide surge with the occurrence of
      MMCs in term infants. In the second study we assessed whether erythromycin, a
      motilin receptor agonist, could induce migrating motor activity in preterm and
      term infants. In the first study we recorded motor activity in nine term infants
      who had never been fed. We determined plasma concentrations of motilin and
      pancreatic polypeptide in the presence and absence of MMCs. In the second study
      we gave the motilin agonist erythromycin intragastrically to 21 infants at a
      range of 24-42 wk of gestation to assess whether migrating activity could be
      induced via the motilin receptor. In the first study, plasma concentrations of
      motilin were similar during the presence and absence of MMCs, as were plasma
      concentrations of pancreatic polypeptide. In the second study, the administration
      of erythromycin induced the appearance of migrating activity in 7 of 14 infants
      who were older than 32 wk but in none of the infants who was younger than 32 wk.
      Although the motilin receptor appears to be functionally present beyond 32 wk of
      gestation, as assessed by in indirect pharmacologic challenge, hormonal
      modulation of migrating activity in the neonate by plasma motilin and pancreatic
      polypeptide is absent.

PMID- 9284277
TI  - Expression and glucocorticoid regulation of surfactant protein C in human fetal
      lung.
AB  - The hydrophobic surfactant protein C (SP-C) is known to modulate the biophysical
      properties of surfactant phospholipid. Although SP-C mRNA has been demonstrated
      in human fetal lung, there is limited information regarding developmental
      expression and processing of proSP-C protein. Two epitope-specific human proSP-C
      antisera, anti-hCPROSP-C (His59-Ser72) and anti-hCTERMSP-C (Gly162-Gly175), were
      generated to complement previously produced anti-NPROSP-C (Met10-Gln23) for the
      study of proSP-C expression in human fetal lung. Western blotting and
      immunocytochemistry detected expression of proSP-C protein by 12-16 wk of
      gestation. ProSP-C immunoreactivity of preculture lung, limited to expression of
      proSP-C21 in airway epithelial cells, was markedly enhanced by culture of lung
      explants in dexamethasone. To examine synthesis of proSP-C, homogenates from
      explants were labeled with 35S-Met/Cys for 0.5-4 h. Immunoprecipitation with anti
      NPROSP-C detected 35S-proSP-C21 by 30 min and, after 2 h of labeling, there was a
      15-fold increase in 35S-proSP-C21 in dexamethasone-treated lungs versus controls.
      Synthesis of proSP-C21 was followed by the appearance of a 24-kD form and smaller
      processing intermediates including 6-10-kD forms. Posttranslational processing of
      proSP-C21 was not observed in control explants. SP-C(6-10) were not recognized by
      either anti-CPROSP-C or anti-hCTERMSP-C. These results indicate that low level
      expression of proSP-C protein first occurs in epithelial cells early in the
      second trimester and that expression can be enhanced by dexamethasone. Initial
      posttranslational processing of human proSP-C involves modification of proSP-C21
      to SP-C24 and subsequent proteolysis of C-terminal propeptide domains. We
      speculate that absence of low Mr intermediates in unstimulated second trimester
      fetal lung tissue reflects developmental and glucocorticoid dependent regulation
      of proSP-C21 synthesis and posttranslational processing.

PMID- 9284279
TI  - Postnatal catch-up growth induced by growth hormone and insulin-like growth
      factor-I in rats with intrauterine growth retardation caused by maternal protein
      malnutrition.
AB  - In this study, we examined the effects of exogenous IGF-I and GH on postnatal
      growth of rat pups with intrauterine growth retardation due to gestational
      protein restriction. From birth until weaning (d 23), pups born from dams fed ad
      libitum a low (5% casein; P5 pups) or a normal protein diet (20% casein; P20
      controls) were cross-fostered to well nourished lactating dams. On d 2, the
      litters (n = 6/dietary group) were reduced in size to 6 pups, and littermates
      received, through postnatal d 23, two daily s.c. injections of bovine GH (2.5
      microg/g of body weight (BW)/day), human IGF-I (1.8 microg/g of BW/day), or
      saline. At birth, BW and tail length (TL) of P5 pups were markedly decreased (to
      72 and 70% of controls, respectively; p < 0.001). Despite food rehabilitation,
      stunting of body growth was still apparent on d 23 in the saline-injected P5 rats
      (BW and TL: 76 and 83% of age-matched saline-injected controls; p < 0.01). Serum
      IGF-I (-51%; p < 0.001) and weight of liver, heart, kidney, brain, and thymus (
      13 to -35%; p < 0.01) were also reduced. Administration of GH in P5 rats raised
      their serum IGF-I (1-fold) to levels observed in saline-injected controls, and
      restored normal BW and TL (94 and 98% of controls, respectively), and organ
      weight (91-107% of those of controls). Injections of IGF-I in P5 rats increased
      after 1 h their serum IGF-I to levels 3 times greater than in saline-injected
      controls, and resulted in normalization of BW and TL (94 and 96% of controls),
      and organ weight (92-111% of controls). In P20 controls, 3-wk GH and IGF-I
      injections significantly increased serum IGF-I (0.6- and 2-fold increases,
      respectively), BW (14 and 11%), TL (12 and 11%), and organ weight (+10 to 30%)
      compared with saline-injected rats (p < 0.01). We conclude that under conditions
      of adequate nutrition, both GH and IGF-I may equally promote postnatal catch-up
      growth in rats with intrauterine growth retardation caused by gestational protein
      malnutrition.

PMID- 9284280
TI  - Intellectual, neurologic, and neuropsychologic outcome in untreated subjects with
      nonphenylketonuria hyperphenylalaninemia. German Collaborative Study on
      Phenylketonuria.
AB  - Based on the serum phenylalanine levels under free diet patients with
      hyperphenylalaninemia are classified as "classical" (>1200 micromol/L), "mild"
      (600-1200 micromol/L), or "non-phenylketonuria (PKU)-hyperphenylalaninemia" (<600
      micromol/L). Recent studies revealed intellectual, neurologic, and
      neuropsychologic deficits as well as abnormalities of cerebral white matter
      (magnetic resonance imaging, MRI) in patients with early and adequately treated
      PKU. In addition deficits in IQ were reported for a group of 4-y-old patients
      with untreated mild PKU and non-PKU hyperphenylalaninemia (serum phenylalanine
      levels below 900 micromol/L). As a consequence, a lifelong diet with serum
      phenylalanine levels below 400 micromol/L was recommended even for those patients
      with serum phenylalanine levels remaining consistently between 400 and 600
      micromol/L. Generally patients with non-PKU hyperphenylalaninemia were not
      treated, as a normal outcome was suspected, but the clinical development of
      patients with non-PKU hyperphenylalaninemia was not so far studied
      systematically. We assessed 28 untreated patients with non-PKU
      hyperphenylalaninemia (age: mean = 21.8, SD = 4.2 y) for IQ, school and job
      career, clinical-neurologic development, fine motor performances, selective and
      sustained attention, as well as for frontal lobe-dependent "executive functions."
      In addition, cranial MRI was obtained in 10 of these patients. Compared with
      healthy control subjects, matched for age, sex, and socioeconomic status, the
      patients reached normal results in all clinical and psychometric tests. Cranial
      MRI revealed no abnormalities. Additionally, no significant correlations between
      serum phenylalanine levels and test results were obtained. In the absence of any
      demonstrative effect, treatment is unlikely to be of significant effect in
      patients with non-PKU hyperphenylalaninemia.

PMID- 9284282
TI  - Molecular dynamics study of time-correlated protein domain motions and molecular
      flexibility: cytochrome P450BM-3.
AB  - Time-correlated atomic motions were used to characterize protein domain
      boundaries from atomic coordinates generated by molecular dynamics simulations. A
      novel application of the dynamical cross-correlation matrix (DCCM) analysis tool
      was used to help identify putative protein domains. In implementing this new
      approach, several DCCM maps were calculated, each using a different coordinate
      reference frame from which protein domain boundaries and protein domain residue
      constituents could be identified. Cytochrome P450BM-3, from Bacillus megaterium,
      was used as the model protein in this study. The analyses indicated that the
      simulated protein comprises three distinct domain regions; in contrast, only two
      protein domains were identified in the original crystal structure report.
      Specifically, the DCCM analyses showed that the F-G helix region was a separate
      domain entity and not a part of the alpha domain, as previously designated. The
      simulations demonstrated that the domain motions of the F-G helix region effected
      both the size and shape of the enzyme active site, and that the dynamics of the F
      G helix domain could possibly control access of substrate to the binding pocket.

PMID- 9284281
TI  - A general computational framework for modeling cellular structure and function.
AB  - The "Virtual Cell" provides a general system for testing cell biological
      mechanisms and creates a framework for encapsulating the burgeoning knowledge
      base comprising the distribution and dynamics of intracellular biochemical
      processes. It approaches the problem by associating biochemical and
      electrophysiological data describing individual reactions with experimental
      microscopic image data describing their subcellular localizations. Individual
      processes are collected within a physical and computational infrastructure that
      accommodates any molecular mechanism expressible as rate equations or membrane
      fluxes. An illustration of the method is provided by a dynamic simulation of IP3
      mediated Ca2+ release from endoplasmic reticulum in a neuronal cell. The results
      can be directly compared to experimental observations and provide insight into
      the role of experimentally inaccessible components of the overall mechanism.

PMID- 9284283
TI  - Kinetics of release of serotonin from isolated secretory granules. I.
      Amperometric detection of serotonin from electroporated granules.
AB  - We developed a method for measuring the efflux of 5-hydroxytryptamine (5-HT,
      serotonin) from isolated intact granules of the mast cell of the beige mouse.
      This method combines electroporation of the vesicle membrane with amperometric
      detection of 5-HT. A single secretory granule is placed between two platinum
      electrodes (distance approximately 100 microm) and positioned adjacent (<1
      microm) to a carbon fiber microelectrode. A short (approximately 30 micros) high
      intensity voltage pulse (electric field of approximately 5 kV/cm) is delivered to
      the electrodes to trigger the mechanical breakdown of the granule membrane, which
      activates the release of 5-HT. We observed concurrent swelling of the granule
      matrix with the oxidation of 5-HT at the carbon fiber electrode (overpotential +
      650 mV). Similar to the release of secretory products during exocytosis, the
      oxidation current exhibits a spike-like time course with a noninstantaneous
      rising phase (time between onset of current and maximum flux, t(max)) with
      approximately 25% of the molecules released during this period. When the current
      reaches its maximum, the granule matrix attains its maximum swollen state. We
      found that the rising phase depends on the initial cross-sectional area of the
      granule (t(max) approximately 21r2) and reflects the time required for membrane
      rupture. The average t(1/2)spike of the amperometric spikes was found to be
      approximately 150 ms, which is 3-7 times faster than the t(1/2) measured during
      cellular exocytosis.

PMID- 9284284
TI  - Kinetics of release of serotonin from isolated secretory granules. II. Ion
      exchange determines the diffusivity of serotonin.
AB  - We measured the efflux of 5-hydroxytryptamine (5-HT, serotonin) from an intact
      secretory granule extracted from the mast cell of the beige mouse. The efflux was
      measured with amperometry after rupture of the granule membrane was triggered by
      electroporation. We determined the diffusivity of 5-HT within the secretory
      granule to be 2.0 x 10(-8) cm2 s(-1) when the granule is in contact with a
      physiological saline and found that this diffusivity depends on the valence of
      the cation in the external electrolyte. There is a fivefold increase in the
      diffusion coefficient of 5-HT determined in CsCl (150 mM, pH 7.2) at 3.7 x 10(-8)
      cm2 s(-1) compared to that determined in histamine dihydrochloride (Hi, 100 mM at
      pH 4.5) at 0.7 x 10(-8) cm2 s(-1). We found that the rate of expansion of the
      granule matrix observed in physiological medium correlates with the efflux of 5
      HT, and that the rate of swelling of the matrix and the efflux depend on the
      microviscosity within the granule matrix and not the bulk viscosity of the
      external solution. The low diffusivity of 5-HT (approximately 500-fold less than
      in the bulk), the observation that the valence of the counterion affects this
      diffusivity, and the relationship between the volume changes of the matrix and
      the efflux suggest that 5-HT is released from the granule by ion exchange. We
      discuss the implications of this result for exocytotic release in mast cells and
      propose that an ion exchange mechanism could control the rate of release in other
      secretory systems.

PMID- 9284285
TI  - Imaging and manipulation of high-density lipoproteins.
AB  - The atomic force microscope (AFM) has been used to image a variety of biological
      systems, but has rarely been applied to soluble protein-lipid complexes. One of
      the primary physiological protein-lipid complexes is the high-density
      lipoproteins (HDL), responsible for the transport of cholesterol from the
      peripheral tissues and other lipoproteins to the liver. We have used the AFM to
      directly image discoidal reconstituted HDL (rHDL) particles for the first time.
      The height of these particles is consistent with a phospholipid bilayer
      structure, but careful high resolution measurements of particle diameters has
      indicated that they fuse when adsorbed to mica. Furthermore, it has been
      demonstrated that the AFM can be used to initiate this bilayer fusion in a
      controlled manner, allowing the fabrication of stabilized, nanometer scale,
      phospholipid bilayer "domains."

PMID- 9284287
TI  - The source of NMR-detected motional anisotropy of water in blood vessel walls.
AB  - 2H Double quantum-filtered (DQF) NMR spectroscopy of deuterated water is
      sensitive to the presence of order in biological systems. This is because the
      only nuclei that are detected are those with residual quadrupolar interactions
      due to their anisotropic motion. In the present study, samples of aorta, coronary
      and carotid arteries, and vena cava were studied in parallel by 2H DQF NMR and by
      light microscopy. The average quadrupolar splitting, calculated from the NMR
      data, varies considerably among the different blood vessels, with high
      reproducibility for each type of vessel. Polarization microscopy examinations
      using collagen-specific staining with picrosirius red, have shown a variety of
      color profiles for the different blood vessels. These reflect different physical
      modes of aggregation (packing and thickness) of collagen fibers. A correlation
      was found between the NMR parameters and the color profiles of the picrosirius
      red-stained sections. Treating the blood vessels with 90% formic acid resulted in
      the elimination of the 2H DQF NMR signal. Histological analysis demonstrated a
      complete degradation of collagen and muscle, whereas the elastin filaments were
      preserved. Evidence is given that the 2H DQF NMR signal is dominated by the
      contribution of water molecules interacting with the collagen fibers.

PMID- 9284289
TI  - AOTF microscope for imaging with increased speed and spectral versatility.
AB  - We have developed a new fluorescence microscope that addresses the spectral and
      speed limitations of current light microscopy instrumentation. In the present
      device, interference and neutral density filters normally used for fluorescence
      excitation and detection are replaced by acousto-optic tunable filters (AOTFs).
      Improvements are described, including the use of a dispersing prism in
      conjunction with the imaging AOTF and an oblique-illumination excitation scheme,
      which together enable the AOTF microscope to produce images comparable to those
      obtained with conventional fluorescence instruments. The superior speed and
      spectral versatility of the AOTF microscope are demonstrated by a ratio image
      pair acquired in 3.5 ms and a micro-spectral absorbance measurement of hemoglobin
      through a cranial window in a living mouse.

PMID- 9284288
TI  - Cell viability and probe-cell membrane interactions of XR1 glial cells imaged by
      atomic force microscopy.
AB  - As atomic force microscopy (AFM) imaging of live specimens becomes more
      commonplace, at least two important questions arise: 1) do live specimens remain
      viable during and after AFM, and 2) is there transfer of membrane components from
      the cell to the AFM probe during probe-membrane interactions? We imaged live XR1
      glial cells in culture by single- or dual-pass contact or tapping-mode AFM,
      examined cell viability at various postimaging times, and report that AFM-imaged
      live XR1 cells remained viable up to 48 h postimaging and that cell death rates
      did not increase. To determine if nonlethal, transient interactions between the
      AFM probe and cell membrane led to transfer of XR1 cell membrane phospholipid
      components on the probe, we treated the scanned probes with the lipid-binding
      fluorophore FM 1-43. Confocal microscopy revealed that phospholipid membrane
      components did accumulate on the probe, and to a generally greater extent during
      contact-mode imaging than during tapping-mode imaging. Moreover, membrane
      accumulations on the probe were greater when live XR1 cells were damaged or
      perturbed, yet membrane did not accumulate in fluorescently detectable quantities
      during repeated "force curves" during control experiments. Taken together, our
      data indicate that although AFM imaging of live cells in culture does not affect
      long-term cell viability, there are substantial probe-membrane interactions that
      lead to transfer of membrane components to the probe.

PMID- 9284286
TI  - Ligand-induced receptor dimerization may be critical for signal transduction by
      choriogonadotropin.
AB  - A mechanism of signal transduction by human choriogonadotropin (hCG) has been
      proposed. Competitive inhibition of the binding of hCG to its receptor by the
      serine protease inhibitors led to the identification of local structural homology
      of an extracellular region of the receptor with the reactive site loop of
      chymotrypsin inhibitor. Synthetic peptides from the extracellular domain of
      luteinizing hormone-choriogonadotropin (LH/CG) receptor, rationally designed on
      the basis of this homology, were found to affect hormone-receptor binding and
      bioactivity. A receptor peptide incorporating one complete structural unit of the
      leucine-rich repeats motif of the extracellular domain of the receptor
      significantly increased hCG-receptor binding in a dose-dependent manner. However,
      the testosterone production in a Leydig cell bioassay was inhibited in the
      presence of this peptide. The agonistic effect on the hCG-receptor binding and
      the antagonistic effect on the testosterone production of a receptor peptide
      suggests the possibility of more than one quasi-equivalent receptor-binding site
      on the hormone. Hormone-induced receptor oligomerization may therefore be
      involved in the mechanism of signal transduction by hCG.

PMID- 9284290
TI  - Near-simultaneous hemoglobin saturation and oxygen tension maps in mouse brain
      using an AOTF microscope.
AB  - A newly developed microscope using acousto-optic tunable filters (AOTFs) was used
      to generate in vivo hemoglobin saturation (SO2) and oxygen tension (PO2) maps in
      the cerebral cortex of mice. SO2 maps were generated from the spectral analysis
      of reflected absorbance images collected at different wavelengths, and PO2 maps
      were generated from the phosphorescence lifetimes of an injected palladium
      porphyrin compound using a frequency-domain measurement. As the inspiratory O2
      was stepped from hypoxia (10% O2), through normoxia (21% O2), to hyperoxia (60%
      O2), measured SO2 and PO2 levels rose accordingly and predictably throughout. A
      plot of SO2 versus PO2 in different arterial and venous regions of the pial
      vessels conformed to the sigmoidal shape of the oxygen-hemoglobin dissociation
      curve, providing further validation of the two mapping procedures. The study
      demonstrates the versatility of the AOTF microscope for in vivo physiologic
      investigation, allowing for the generation of nearly simultaneous SO2 and PO2
      maps in the cerebral cortex, and the frequency-domain detection of
      phosphorescence lifetimes. This class of study opens up exciting new
      possibilities for investigating the dynamics of hemoglobin and O2 binding during
      functional activation of neuronal tissues.

PMID- 9284291
TI  - Velocity-curvature relationship of colliding spherical calcium waves in rat
      cardiac myocytes.
AB  - Colliding spherical calcium waves in enzymatically isolated rat cardiac myocytes
      develop new wavefronts propagating perpendicular to the original direction. When
      investigated by confocal laser scanning microscopy (CLSM), using the fluorescent
      Ca2+ indicator fluo-3 AM, "cusp"-like structures become visible that are
      favorably approximated by double parabolae. The time-dependent position of the
      vertices is used to determine propagation velocity and negative curvature of the
      wavefront in the region of collision. It is evident that negatively curved waves
      propagate faster than positively curved, single waves. Considering two perfectly
      equal expanding circular waves, we demonstrated that the collision of calcium
      waves is due to an autocatalytic process (calcium-induced calcium release), and
      not to a simple phenomenon of interference. Following the spatiotemporal
      organization in simpler chemical systems maintained under conditions far from the
      thermodynamic equilibrium (Belousov-Zhabotinskii reaction), the dependence of the
      normal velocity on the curvature of the spreading wavefront is given by a linear
      relation. The so-called velocity-curvature relationship makes clear that the
      velocity is enhanced by curvature toward the direction of forward propagation and
      decreased by curvature away from the direction of forward propagation (with an
      influence of the diffusion coefficient). Experimentally obtained velocity data of
      both negatively and positively curved calcium waves were approximated by
      orthogonal weighted regression. The negative slope of the straight line resulted
      in an effective diffusion coefficient of 1.2 x 10(-4) mm2/s. From the so-called
      critical radius, which must be exceeded to initiate a traveling calcium wave, a
      critical volume (with enhanced [Ca2+]i) of approximately 12 microm3 was
      calculated. This is almost identical to the volume that is occupied by a single
      calcium spark.

PMID- 9284293
TI  - On the calculation of magnetic fields based on multipole modeling of focal
      biological current sources.
AB  - Spatially restricted biological current distributions, like the primary neuronal
      response in the human somatosensory cortex evoked by electric nerve stimulation,
      can be described adequately by a current multipole expansion. Here analytic
      formulas are derived for computing magnetic fields induced by current multipoles
      in terms of an nth-order derivative of the dipole field. The required
      differential operators are given in closed form for arbitrary order. The concept
      is realized in different forms for an expansion of the scalar as well as the
      dyadic Green's function, the latter allowing for separation of those multipolar
      source components that are electrically silent but magnetically detectable. The
      resulting formulas are generally applicable for current sources embedded in
      arbitrarily shaped volume conductors. By using neurophysiologically relevant
      source parameters, examples are provided for a spherical volume conductor with an
      analytically given dipole field. An analysis of the signal-to-noise ratio for
      multipole coefficients up to the octapolar term indicates that the lateral extent
      of cortical current sources can be detected by magnetoencephalographic
      recordings.

PMID- 9284292
TI  - Endogenous buffers limit the spread of free calcium in hair cells.
AB  - Mobile Ca2+ buffers in hair cells have been postulated to play a dual role. On
      one hand, they carry incoming Ca2+ away from synaptic areas, allowing synapses to
      be rapidly reset. On the other hand, they limit the spread of free Ca2+ into the
      cell, preventing cross-talk between different pathways that employ Ca2+ as a
      second messenger. We have obtained evidence for such mobile Ca2+ buffers in hair
      cells by comparing the patterns of Ca2+-induced fluo-3 fluorescence under whole
      cell and perforated-patch recording conditions. Fluorescent signals under
      perforated-patch conditions are relatively weak and are limited to the immediate
      vicinity of the membrane. These observations can be explained by a diffusion
      reaction scheme that, in addition to Ca2+ and fluo-3, incorporates endogenous
      fixed and mobile Ca2+ buffers. Our experiments also suggest that the mobility of
      the endogenous buffer might be higher than previously thought. A high buffer
      mobility is expected to enhance the cell's ability to rapidly modulate
      transmitter release.

PMID- 9284294
TI  - Generation of action potentials in a mathematical model of corticotrophs.
AB  - Corticotropin-releasing hormone (CRH) is an important regulator of
      adrenocorticotropin (ACTH) secretion from pituitary corticotroph cells. The
      intracellular signaling system that underlies this process involves modulation of
      voltage-sensitive Ca2+ channel activity, which leads to the generation of Ca2+
      action potentials and influx of Ca2+. However, the mechanisms by which Ca2+
      channel activity is modulated in corticotrophs are not currently known. We
      investigated this process in a Hodgkin-Huxley-type mathematical model of
      corticotroph plasma membrane electrical responses. We found that an increase in
      the L-type Ca2+ current was sufficient to generate action potentials from a
      previously resting state of the model. The increase in the L-type current could
      be elicited by either a shift in the voltage dependence of the current toward
      more negative potentials, or by an increase in the conductance of the current.
      Although either of these mechanisms is potentially responsible for the generation
      of action potentials, previous experimental evidence favors the former mechanism,
      with the magnitude of the shift required being consistent with the experimental
      findings. The model also shows that the T-type Ca2+ current plays a role in
      setting the excitability of the plasma membrane, but does not appear to
      contribute in a dynamic manner to action potential generation. Inhibition of a K+
      conductance that is active at rest also affects the excitability of the plasma
      membrane.

PMID- 9284296
TI  - Reconstructing potential energy functions from simulated force-induced unbinding
      processes.
AB  - One-dimensional stochastic models demonstrate that molecular dynamics simulations
      of a few nanoseconds can be used to reconstruct the essential features of the
      binding potential of macromolecules. This can be accomplished by inducing the
      unbinding with the help of external forces applied to the molecules, and
      discounting the irreversible work performed on the system by these forces. The
      fluctuation-dissipation theorem sets a fundamental limit on the precision with
      which the binding potential can be reconstructed by this method. The uncertainty
      in the resulting potential is linearly proportional to the irreversible component
      of work performed on the system during the simulation. These results provide an a
      priori estimate of the energy barriers observable in molecular dynamics
      simulations.

PMID- 9284295
TI  - The choline-leakage hypothesis for the loss of acetylcholine in Alzheimer's
      disease.
AB  - We present a hypothesis for the loss of acetylcholine in Alzheimer's disease that
      is based on two recent experimental results: that beta-amyloid causes leakage of
      choline across cell membranes and that decreased production of acetylcholine
      increases the production of beta-amyloid. According to the hypothesis, an
      increase in beta-amyloid concentration caused by proteolysis of the amyloid
      precursor protein results in an increase in the leakage of choline out of cells.
      This leads to a reduction in intracellular choline concentration and hence a
      reduction in acetylcholine production. The reduction in acetylcholine production,
      in turn, causes an increase in the concentration of beta-amyloid. The resultant
      positive feedback between decreased acetylcholine and increased beta-amyloid
      accelerates the loss of acetylcholine. We compare the predictions of the choline
      leakage hypothesis with a number of experimental observations. We also
      approximate it with a pair of ordinary differential equations. The solutions of
      these equations indicate that the loss of acetylcholine is very sensitive to the
      initial rate of beta-amyloid production.

PMID- 9284297
TI  - A random-walk model for retardation of interacting species during gel
      electrophoresis: implications for gel-shift assays.
AB  - We recently showed that intermolecular DNA triplexes can form during gel
      electrophoresis when a faster migrating single strand overtakes a slower
      migrating band containing a duplex of appropriate sequence. We proposed a model
      to account for the resulting apparent comigration of triplexes with the duplex
      band when the lifetime of the triplex is much shorter than the time of
      electrophoresis. The model predicts that short-lived complexes can be detected by
      a gel-shift assay if the faster migrating component of the complex is labeled, a
      slower migrating component is in excess, and the complex itself migrates more
      slowly than either of the components. In this case the labeled component, after
      dissociation from the complex, overtakes a slower migrating band of the free,
      unlabeled second component and can be captured by the unlabeled component and
      again retarded; after dissociation of the newly formed complex the cycle is
      repeated. If the concentration of unlabeled component in the band is larger than
      some critical value (c(cr)), most of the labeled component becomes trapped in
      this band during the entire time of gel electrophoresis, thus effectively
      comigrating with the slower migrating unlabeled component. We call this mechanism
      of comigration "cyclic capture and dissociation" (CCD). Here we present a
      quantitative analysis of the model of CCD comigration which predicts that CCD
      comigration can be used not only for the detection of relatively short-lived
      complexes, but also for estimation of the specificity of complex formation.

PMID- 9284298
TI  - Pore disappearance in a cell after electroporation: theoretical simulation and
      comparison with experiments.
AB  - The process of pore disappearance after cell electroporation is analyzed
      theoretically. On the basis of the kinetic model, in which the formation and
      annihilation of a metastable hydrophilic pore are considered as random one-step
      processes, a distribution function of cell resealing times, Fr(t), is derived.
      Two cases are studied: 1) the rate of pore resealing, k(r), is significantly
      greater than the rate of pore formation, k(f); and 2) the rate of pore formation,
      k(f), is comparable with k(r). It is determined that the shape of the
      distribution function depends on the initial number of pores in a cell, n(i). If
      in the absence of an external electric field the rate of pore formation, k(f), is
      significantly less than the rate of pore resealing, k(r) (case 1), pores
      disappear completely, whereas when k(f) approximately k(r) (case 2), the cell
      achieves a steady state in which the number of pores is equal to k(f)/k(r). In
      case 1, when n(i) = 1, the distribution function Fr(t) is exponential. The
      developed theory is compared with experimental data available in the literature.
      Increasing the time of incubation at elevated temperature increases the fraction
      of resealed cells. This indicates that the time necessary for the resealing
      varies from cell to cell. Although the shape of experimental relationships
      depends on the electroporation conditions they can be described by theoretical
      curves quite well. Thus it can be concluded that the disappearance of pores in
      the cell membrane after electroporation is a random process. It is shown that
      from the comparison of presented theory with experiments, the following
      parameters can be estimated: the average number of pores, n(i), that appeared in
      a cell during an electric pulse; the rate of pore disappearance, k(r); the ratio
      k(f)/k(r); and the energy barrier to pore disappearance deltaWr(0). Estimated
      numerical values of the parameters show that increasing the amplitude of an
      electric pulse increases either the apparent number of pores created during the
      pulse (the rate of pore resealing remains the same) or the rate of pore resealing
      (the average number of pores remains the same).

PMID- 9284299
TI  - Gramicidin channels in phospholipid bilayers with unsaturated acyl chains.
AB  - In organic solvents gramicidin A (gA) occurs as a mixture of slowly
      interconverting double-stranded dimers. Membrane-spanning gA channels, in
      contrast, are almost exclusively single-stranded beta(6,3)-helical dimers. Based
      on spectroscopic evidence, it has previously been concluded that the
      conformational preference of gA in phospholipid bilayers varies as a function of
      the degree of unsaturation of the acyl chains. Double-stranded pi pi(5,6)-helical
      dimers predominate (over single-stranded beta(6,3)-helical dimers) in lipid
      bilayer membranes with polyunsaturated acyl chains. We therefore examined the
      characteristics of channels formed by gA in 1-palmitoyl-2
      oleoylphosphatidylcholine/n-decane, 1,2-dioleoylphosphatidylcholine/n-decane, and
      1,2-dilinoleoylphosphatidylcholine/n-decane bilayers. We did not observe long
      lived channels that could be conducting double-stranded pi pi(5,6)-helical dimers
      in any of these different membrane environments. We conclude that the single
      stranded beta(6,3)-helical dimer is the only conducting species in these
      bilayers. Somewhat surprisingly, the average channel duration and channel-forming
      potency of gA are increased in dilinoleoylphosphatidylcholine/n-decane bilayers
      compared to 1-palmitoyl-2-oleoylphosphatidylcholine/n-decane and
      dioleoylphosphatidylcholine/n-decane bilayers. To test for specific interactions
      between the aromatic side chains of gA and the acyl chains of the bilayer, we
      examined the properties of channels formed by gramicidin analogues in which the
      four tryptophan residues were replaced with naphthylalanine (gN), tyrosine (gT),
      and phenylalanine (gM). The results show that all of these analogue channels
      experience the same relative stabilization when going from
      dioleoylphosphatidylcholine to dilinoleoylphosphatidylcholine bilayers.

PMID- 9284300
TI  - Deletion of amino acids 1641-2437 from the foot region of skeletal muscle
      ryanodine receptor alters the conduction properties of the Ca release channel.
AB  - The ryanodine receptor (RyR) of skeletal muscle contains two functional domains:
      a carboxyl-terminal hydrophobic domain that forms the putative conduction pore of
      the calcium release channel, and a large cytoplasmic domain that corresponds to
      the "foot structure." To understand the contribution of the foot structure to the
      function of the calcium release channel, we studied a RyR deletion mutant,
      delta(1641-2437)-RyR, in which a region that is rich in glutamate and aspartate
      residues (a.a. 1641-2437) was removed. The wild-type and delta(1641-2437)-RyR
      proteins were expressed in a Chinese hamster ovary (CHO) cell line, and functions
      of single calcium release channels were measured in the lipid bilayer membrane.
      The wild-type RyR forms functional calcium release channels with a linear current
      voltage relationship similar to that of the native channel identified in the
      sarcoplasmic reticulum membrane of skeletal muscle, whereas the channels formed
      by delta(1641-2437)-RyR exhibit significant inward rectification, i.e., currents
      moving from cytoplasm into SR lumen were approximately 20% less than that in the
      opposite direction. As in to the wt-RyR channel, opening of the delta(1641-2437)
      RyR channel has a bell-shaped dependence on the cytoplasmic calcium, but the
      calcium-dependent activation and inactivation processes of the delta(1641-2437)
      RyR channel are shifted to higher calcium concentrations. Our data show that
      deletion of a.a. 1641-2437 from the foot region of the skeletal muscle RyR
      results in changes in both ion conduction and calcium-dependent regulation of the
      calcium release channel.

PMID- 9284301
TI  - Functional calcium release channel formed by the carboxyl-terminal portion of
      ryanodine receptor.
AB  - The ryanodine receptor (RyR) is one of the key proteins involved in excitation
      contraction (E-C) coupling in skeletal muscle, where it functions as a Ca2+
      release channel in the sarcoplasmic reticulum (SR) membrane. RyR consists of a
      single polypeptide of approximately 560 kDa normally arranged in a homotetrameric
      structure, which contains a carboxyl (C)-terminal transmembrane domain and a
      large amino (N)-terminal cytoplasmic domain. To test whether the carboxyl
      terminal portion of RyR is sufficient to form a Ca2+ release channel, we
      expressed the full-length (RyR-wt) and C-terminal (RyR-C, approximately 130 kDa)
      RyR proteins in a Chinese hamster ovary (CHO) cell line, and measured their Ca2+
      release channel functions in planar lipid bilayer membranes. The single-channel
      properties of RyR-wt were found to be similar to those of RyR from skeletal
      muscle SR. The RyR-C protein forms a cation-selective channel that shares some of
      the channel properties with RyR-wt, including activation by cytoplasmic Ca2+ and
      regulation by ryanodine. Unlike RyR-wt, which exhibits a linear current-voltage
      relationship and inactivates at millimolar Ca2+, the channels formed by RyR-C
      display significant inward rectification and fail to close at high cytoplasmic
      Ca2+. Our results show that the C-terminal portion of RyR contains structures
      sufficient to form a functional Ca2+ release channel, but the N-terminal portion
      of RyR also affects the ion-conduction and calcium-dependent regulation of the
      Ca2+ release channel.

PMID- 9284302
TI  - Permeation through the calcium release channel of cardiac muscle.
AB  - Current voltage (I-V) relations were measured from the calcium release channel
      (CRC) of the sarcoplasmic reticulum of cardiac muscle in 12 KCl solutions,
      symmetrical and asymmetrical, from 25 mM to 2 M. I-V curves are nearly linear, in
      the voltage range +/- 150 mV approximately 12kT/e, even in asymmetrical
      solutions, e.g., 2 M // 100 mM. It is awkward to describe straight lines as sums
      of exponentials in a wide range of solutions and potentials, and so traditional
      barrier models have difficulty fitting this data. Diffusion theories with
      constant fields predict curvilinear I-V relations, and so they are also
      unsatisfactory. The Poisson and Nernst-Planck equations (PNP) form a diffusion
      theory with variable fields. They fit the data by using adjustable parameters for
      the diffusion constant of each ion and for the effective density of fixed (i.e.,
      permanent) charge P(x) along the channel's "filter" (7-A diameter, 10 A long). If
      P(x) is described by just one parameter, independent of x (i.e., P(x) = P0 = -4.2
      M), the fits are satisfactory (RMS error/RMS current = 6.4/67), and the estimates
      of diffusion coefficients are reasonable D(K) = 1.3 x 10(-6) cm2/s, D(Cl) = 3.9 x
      10(-6) cm2/s. The CRC seems to have a small selectivity filter with a very high
      density of permanent charge. This may be a design principle of channels
      specialized for large flux. The Appendix derives barrier models, and their
      prefactor, from diffusion theories (with variable fields) and argues that barrier
      models are poor descriptions of CRCs in particular and open channels in general.

PMID- 9284303
TI  - A novel calcium-sensing domain in the BK channel.
AB  - The high-conductance Ca2+-activated K+ channel (mSlo) plays a vital role in
      regulating calcium entry in many cell types. mSlo channels behave like voltage
      dependent channels, but their voltage range of activity is set by intracellular
      free calcium. The mSlo subunit has two parts: a "core" resembling a subunit from
      a voltage-dependent K+ channel, and an appended "tail" that plays a role in
      calcium sensing. Here we present evidence for a site on the tail that interacts
      with calcium. This site, the "calcium bowl," is a novel calcium-binding motif
      that includes a string of conserved aspartate residues. Mutations of the calcium
      bowl fall into two categories: 1) those that shift the position of the G-V
      relation a similar amount at all [Ca2+], and 2) those that shift the position of
      the G-V relation only at low [Ca2+]. None of these mutants alters the slope of
      the G-V curve. These mutant phenotypes are apparent in calcium ion, but not in
      cadmium ion, where mutant and wild type are indistinguishable. This suggests that
      the calcium bowl is sensitive to calcium ion, but insensitive to cadmium ion. The
      presence and independence of a second calcium-binding site is inferred because
      channels still respond to increasing levels of [Ca2+] or [Cd2+], even when the
      calcium bowl is mutationally deleted. Thus a low level of activation in the
      absence of divalent cations is identical in mutant and wild-type channels,
      possibly because of activation of this second Ca2+-binding site.

PMID- 9284305
TI  - Inversion of Markov processes to determine rate constants from single-channel
      data.
AB  - The determination of rate constants from single-channel data can be very
      difficult, in part because the single-channel lifetime distributions commonly
      analyzed by experimenters often have a complicated mathematical relation to the
      channel gating mechanism. The standard treatment of channel gating as a Markov
      process leads to the prediction that lifetime distributions are exponential
      functions. As the number of states of a channel gating scheme increases, the
      number of exponential terms in the lifetime distribution increases, and the
      weights and decay constants of the lifetime distributions become progressively
      more complicated functions of the underlying rate constants. In the present study
      a mathematical strategy for inverting these functions is introduced in order to
      determine rate constants from single-channel lifetime distributions. This
      inversion is easy for channel gating schemes with two or fewer states of a given
      conductance, so the present study focuses on schemes with more states. The
      procedure is to derive explicit equations relating the parameters of the lifetime
      distribution to the rate constants of the scheme. Such equations can be derived
      using the equality between symmetric functions of eigenvalues of a matrix and
      sums over principle minors, as well as expressions for the moments, derivatives,
      and weights of a lifetime distribution. The rate constants are then obtained as
      roots to this system of equations. For a gating scheme with three sequential
      closed states and a single gateway state, exact analytical expressions were found
      for each rate constant in terms of the parameters of the three-exponential closed
      time distribution. For several other gating schemes, systems of equations were
      found that could be solved numerically to obtain the rate constants. Lifetime
      distributions were shown to specify a unique set of real rate constants in
      sequential gating schemes with up to five closed or five open states. For kinetic
      schemes with multiple gating pathways, the analysis of simulated data revealed
      multiple solutions. These multiple solutions could be distinguished by examining
      two-dimensional probability density functions. The utility of the methods
      introduced here are demonstrated by analyzing published data on nicotinic
      acetylcholine receptors, GABA(A) receptors, and NMDA receptors.

PMID- 9284304
TI  - Molecular dynamics study of water and Na+ ions in models of the pore region of
      the nicotinic acetylcholine receptor.
AB  - The nicotinic acetylcholine receptor (nAChR) is an integral membrane protein that
      forms ligand-gated and cation-selective channels. The central pore is lined by a
      bundle of five approximately parallel M2 helices, one from each subunit.
      Candidate model structures of the solvated pore region of a homopentameric
      (alpha7)5 nAChR channel in the open state, and in two possible forms of the
      closed state, have been studied using molecular dynamics simulations with
      restraining potentials. It is found that the mobility of the water is
      substantially lower within the pore than in bulk, and the water molecules become
      aligned with the M2 helix dipoles. Hydrogen-bonding patterns in the pore,
      especially around pore-lining charged and hydrophilic residues, and around
      exposed regions of the helix backbone, have been determined. Initial studies of
      systems containing both water and sodium ions together within the pore region
      have also been conducted. A sodium ion has been introduced into the solvated
      models at various points along the pore axis and its energy profile evaluated. It
      is found that the ion causes only a local perturbation of the water structure.
      The results of these calculations have been used to examine the effectiveness of
      the central ring of leucines as a component of a gate in the closed-channel
      model.

PMID- 9284306
TI  - Control of phobic behavioral responses by rhodopsin-induced photocurrents in
      Chlamydomonas.
AB  - Both phototactic and photophobic responses of Chlamydomonas are mediated by a
      visual system comprising a rhodopsin photoreceptor. Suction pipette recordings
      have revealed that flash stimulation causes calcium currents into the eyespot and
      the flagella. These photocurrents have been suggested to be the trigger for all
      behavioral light responses of the cell. But this has never been shown
      experimentally. Here we describe a detection technique that combines electrical
      and optical measurements from individual algae held in a suction pipette. Thus it
      is possible to record photocurrents and flagellar beating simultaneously and
      establish a direct link between the two. We demonstrate that in Chlamydomonas
      only the photoreceptor current in conjuction with a fast flagellar current
      constitutes the trigger for photophobic responses. Within the time of the action
      potential-like flagellar current, the flagella switch from forward to backward
      swimming, which constitutes the beginning of the photoshock reaction. The switch
      is accompanied by a complex frequency change and beating pattern modulation. The
      results are interpreted in terms of a general model for phototransduction in
      green algae (Chlorophyceae).

PMID- 9284307
TI  - The S5-S6 linker of repeat I is a critical determinant of L-type Ca2+ channel
      conductance.
AB  - The alpha1-subunits of the skeletal and cardiac L-type calcium channels (L
      channels) contain nearly identical pore regions (P-regions) in each of the four
      internal homology repeats. In spite of this high conservation of the P-regions,
      native skeletal L-channels exhibit a unitary conductance that is only about half
      that of native cardiac L-channels. To identify structural determinants of this
      difference in L-channel conductance, we have characterized unitary activity in
      cell-attached patches of dysgenic myotubes expressing skeletal, cardiac, and
      chimeric L-channel alpha1-subunits. Our results demonstrate that the S5-S6 linker
      of repeat I (IS5-IS6 linker) is a critical determinant of the difference in
      skeletal and cardiac unitary conductance. The unitary conductances attributable
      to the wild-type skeletal (CAC6; approximately 14 pS) and cardiac (CARD1;
      approximately 25 pS) alpha1-subunits expressed in dysgenic myotubes are identical
      to those observed in native tissues. Chimeric alpha1-subunits containing skeletal
      sequence for the first internal repeat and all of the putative intracellular
      loops (SkC15), the IS5-IS6 linker and the intracellular loops (SkC51), or only
      the IS5-IS6 linker (SkC49) each exhibit a low, skeletal-like unitary conductance
      (< or = 17 pS). Constructs in which the IS5-IS6 linker is of cardiac origin
      (CARD1 and CSk9) display cardiac-like conductance (approximately 25 pS). Unitary
      conductance and the rate of channel activation are apparently independent
      processes, since both SkC51 and SkC49 exhibit low, skeletal-like conductance and
      rapid, cardiac-like rates of ensemble activation. These results demonstrate that
      the IS5-IS6 linker strongly influences the single channel conductance of L
      channels in a manner that is independent from the rate of channel activation.

PMID- 9284308
TI  - A generalized activating function for predicting virtual electrodes in cardiac
      tissue.
AB  - To fully understand the mechanisms of defibrillation, it is critical to know how
      a given electrical stimulus causes membrane polarizations in cardiac tissue. We
      have extended the concept of the activating function, originally used to describe
      neuronal stimulation, to derive a new expression that identifies the sources that
      drive changes in transmembrane potential. Source terms, or virtual electrodes,
      consist of either second derivatives of extracellular potential weighted by
      intracellular conductivity or extracellular potential gradients weighted by
      derivatives of intracellular conductivity. The full response of passive tissue
      can be considered, in simple cases, to be a convolution of this "generalized
      activating function" with the impulse response of the tissue. Computer
      simulations of a two-dimensional sheet of passive myocardium under steady-state
      conditions demonstrate that this source term is useful for estimating the effects
      of applied electrical stimuli. The generalized activating function predicts
      oppositely polarized regions of tissue when unequally anisotropic tissue is point
      stimulated and a monopolar response when a point stimulus is applied to isotropic
      tissue. In the bulk of the myocardium, this new expression is helpful for
      understanding mechanisms by which virtual electrodes can be produced, such as the
      hypothetical "sawtooth" pattern of polarization, as well as polarization owing to
      regions of depressed conductivity, missing cells or clefts, changes in fiber
      diameter, or fiber curvature. In comparing solutions obtained with an assumed
      extracellular potential distribution to those with fully coupled intra- and
      extracellular domains, we find that the former provides a reliable estimate of
      the total solution. Thus the generalized activating function that we have derived
      provides a useful way of understanding virtual electrode effects in cardiac
      tissue.

PMID- 9284309
TI  - Mapping the distribution of outer hair cell voltage-dependent conductances by
      electrical amputation.
AB  - The mammalian outer hair cell (OHC) functions not only as sensory receptor, but
      also as mechanical effector; this unique union is believed to enhance our ability
      to discriminate among acoustic frequencies, especially in the kilohertz range. An
      electrical technique designed to isolate restricted portions of the plasma
      membrane was used to map the distribution of voltage-dependent conductances along
      the cylindrical extent of the cell. We show that three voltage-dependent
      currents, outward K, I(K,n), and I(Ca) are localized to the basal, synaptic pole
      of the OHC. Previously we showed that the lateral membrane of the OHC harbors a
      dense population of voltage sensor-motor elements responsible for OHC motility.
      This segregation of membrane molecules may have important implications for
      auditory function. The distribution of OHC conductances will influence the cable
      properties of the cell, thereby potentially controlling the voltage magnitudes
      experienced by the motility voltage sensors in the lateral membrane, and thus the
      output of the "cochlear amplifier."

PMID- 9284311
TI  - The structure of divalent cation-induced aggregates of PIP2 and their alteration
      by gelsolin and tau.
AB  - Phosphatidylinositol bisphosphate (PIP2) serves as a precursor for diacylglycerol
      and inositol trisphosphate in signal transduction cascades and regulates the
      activities of several actin binding proteins that influence the organization of
      the actin cytoskeleton. Molecules of PIP2 form 6-nm diameter micelles in water,
      but aggregate into larger, multilamellar structures in physiological
      concentrations of divalent cations. Electron microscopic analysis of these
      aggregates reveals that they are clusters of striated filaments, suggesting that
      PIP2 aggregates form stacks of discoid micelles rather than multilamellar
      vesicles or inverted hexagonal arrays as previously inferred from indirect
      observations. The distance between striations within the filaments varies from
      4.2 to 5.4 nm and the diameter of the filaments depends on the dehydrated ionic
      radius of the divalent cation, with average diameters of 19, 12, and 10 nm for
      filaments formed by Mg2+, Ca2+, and Ba2+, respectively. The structure of the
      divalent cation-induced aggregates can be altered by PIP2 binding proteins.
      Gelsolin and the microtubule associated protein tau both affect the formation of
      aggregates, indicating that tau acts as a PIP2 binding protein in a manner
      similar to gelsolin. In contrast, another PIP2 binding protein, profilin, does
      not modify the aggregates.

PMID- 9284310
TI  - Interaction of the influenza hemagglutinin fusion peptide with lipid bilayers:
      area expansion and permeation.
AB  - Fusion is a crucial event in the infection of animal cells by enveloped viruses
      (e.g., HIV or influenza). Viral fusion is mediated by glycoproteins, spanning the
      viral envelope, which attach to a membrane surface and induce fusion of the viral
      envelope to the cellular membrane. Influenza fusion protein (hemagglutinin)
      contains an amino-terminal segment critical to fusion, referred to as the fusion
      peptide. We show here that the native fusion peptide (wt-20) of hemagglutinin
      destabilizes membranes formed of 99% 1 -stearoyl-2-oleoylphosphatidylcholine
      (SOPC). The first step in destabilization is rapid insertion of the peptide into
      the membrane, in which membrane area increases by as much as 11% in just seconds.
      We visualized and quantified the area expansion by using optical video microscopy
      combined with micropipette aspiration. This rapid membrane area expansion is
      followed by the formation of membrane defects in the size range of 0.5 nm, and
      results in membrane rupture. Both the rate of area increase and maximum area
      increase are significantly higher at a pH near 5.0 compared to pH 7.0. These
      results suggest that enhanced membrane insertion of wt-20 and accompanying area
      expansion at pH 5.0 are responsible for the relatively greater lytic activity at
      this pH. We show that a deletion of the N-terminal glycine of wt-20 results in a
      lack of area expansion or membrane perturbation at pH 5.0.

PMID- 9284313
TI  - The heat of transfer of lipid and surfactant from vesicles into micelles in
      mixtures of phospholipid and surfactant.
AB  - We study the heat associated with the transformation of vesicles into micelles in
      mixtures of bilayer-forming phospholipids and micelle-forming surfactants. We
      subdivide the total heat evolution deltaQ(coex) within the range of coexistence
      of vesicles and micelles into three contributions related to the transition of
      dN(D)m-b molecules of surfactant and dN(L)m-b molecules of lipid from micelles to
      vesicles and to the extraction of dN(D)m-w molecules of surfactant from micelles
      to the aqueous solution, so that deltaQ(coex) = deltaH(D)m-w x dN(D)m-w +
      deltaH(D)m-b x dN(D)m-b + deltaH(L)m-b x dN(L)m-b where deltaH(D)m-w, deltaH(L)m
      b, and deltaH(D)m-b are the respective molar "transfer" enthalpies. We design a
      method for the evaluation of all three molar enthalpies, from isothermal
      calorimetric titrations conducted according to two different protocols of
      titration of lipid-surfactant mixtures. In the first protocol the mixture is
      titrated with an aqueous solution of pure lipid vesicles, and in the second the
      mixture is titrated with an aqueous solution of pure surfactant. Titration of the
      mixed systems by a buffer solution serves to verify the results obtained under
      these protocols. In addition to the values of molar enthalpies, our method yields
      the cmc value of the pure surfactant. We apply our method to investigating the
      heat evolution in mixtures of egg yolk phosphatidylcholine and the nonionic
      surfactant octylglucoside in a phosphate-buffered saline solution at 28 degrees
      C. These studies gave the following values: deltaH(D)m-w = -1732 cal/mol,
      deltaH(L)m-b = -592 cal/mol, deltaH(D)m-b = 645 cal/mol, and cmc = 23.5 mM. We
      discuss the possible physical insight of these values and the perspectives of
      applications of the proposed method.

PMID- 9284312
TI  - Partitioning of octyl glucoside between octyl glucoside/phosphatidylcholine mixed
      aggregates and aqueous media as studied by isothermal titration calorimetry.
AB  - Stepwise dilution of lipid-surfactant mixed micelles first results in extraction
      of surfactant from the mixed micelles into the aqueous medium. Subsequently mixed
      micelles transform into vesicles, within a range of compositions that corresponds
      to equilibrium coexistence between these two types of aggregates. Further
      dilution results in extraction of surfactant from the resultant mixed vesicles.
      In the present study, we have investigated the heat evolution of these processes,
      as they occur in mixed systems composed of egg phosphatidylcholine (PC) and the
      nonionic surfactant octylglucoside (OG). A combined use of isothermal titration
      calorimetry (ITC) and photon correlation spectroscopy (PCS), capable of
      monitoring phase transformations, revealed that 1) The sum of all of the studied
      processes (i.e., extraction of OG from mixed micelles and vesicles and the phase
      transformation) is isocaloric at approximately 40 degrees C throughout the whole
      dilution. At lower temperatures, all of the dilution steps are exothermic,
      whereas at higher temperatures all of them are endothermic. 2) At all
      temperatures, the absolute value of the heat associated with each dilution step
      within the range of coexistence of micelles and vesicles is almost constant and
      larger than in either the micellar or the vesicular range. We give an
      interpretation of these calorimetric data in terms of the relationship between
      the composition of the mixed aggregates Re and the aqueous concentration of
      surfactant monomers Dw. Assuming that the main contribution to the heat evolution
      is due to extraction of surfactant from mixed aggregates to the aqueous solution,
      we deduce the relationship Dw(Re) characterizing the system over the whole range
      of compositions. We find that, in accord with thermodynamic expectations, Dw is
      almost constant throughout the range of coexistence of mixed micelles and
      vesicles.

PMID- 9284314
TI  - The adsorption of Pseudomonas aeruginosa exotoxin A to phospholipid monolayers is
      controlled by pH and surface potential.
AB  - The interaction of Pseudomonas aeruginosa exotoxin A (ETA) with lipid monolayers
      was studied by measuring the variation in surface pressure. ETA adsorbs to the
      monolayer, occupying an average area of approximately 4.6 nm2 per molecule, up to
      a maximum density of one molecule per 28 nm2 of lipid film, which corresponds
      roughly to the cross-sectional area of the toxin. This suggests that ETA
      molecules adsorb until they contact each other, but insert only a small portion
      into the lipid film. The kinetic process could be described by a Langmuir
      adsorption isotherm. The apparent association and dissociation rate constants
      were determined, as were their dependence upon toxin concentration, membrane
      composition, pH, and ionic strength. Two parameters were found to be paramount
      for this interaction: pH and surface potential of the lipid. It appears that ETA
      binding occurs only in a conformational state induced by low pH and is promoted
      by an electrostatic interaction between a positively charged region of the
      protein and the negative charge of acidic phospholipids. On the basis of a simple
      model, the salient features of ETA involved in its adsorption were derived: 1)
      the existence of a conformational state induced by the protonation of a group
      with pK 4.5 +/- 0.2; 2) a positive charge of 1.9 +/- 0.3 e.u. able to interact
      with the surface potential of the membrane; 3) the fraction of potential
      experienced by the protein in the activated state that precedes binding,
      approximately 80%; 4) the intrinsic adsorption and desorption rate constants,
      k(a)0 = (4.8 +/- 0.3) x 10(3) M(-1) s(-1) and k(d)0 = (4.4 +/- 0.4) x 10(-4) s(
      1). These rate constants are independent of pH and lipid and buffer composition,
      and provide a dissociation constant Kd approximately 90 nM.

PMID- 9284315
TI  - The effects of ethylene oxide containing lipopolymers and tri-block copolymers on
      lipid bilayers of dipalmitoylphosphatidylcholine.
AB  - A comparative study is conducted on the influence of two types of polymeric
      compounds on the phase behavior of 1,2-dihexadecanoyl-s,n-glycero-3
      phosphotidylcholine (DC16PC) lipid bilayers. The first polymeric compound is a
      lipopolymer, with two different lengths of a hydrophilic polyethylene oxide
      moity, anchored to the bilayer by a 1,2-dioctadecanoyl-s,n-glycero-3
      phosphoethanolamine (DC18PE) lipid. The second type, which is a novel type of
      membrane-spanning object, is an amphiphilic tri-block copolymer composed of two
      hydrophilic stretches of polyethylene oxide separated by a hydrophobic stretch of
      polystyrene. Hence the tri-block copolymer may act as a membrane-spanning
      macromolecule mimicking an amphiphilic protein or polypeptide. Differential
      scanning calorimetry is used to determine a partial phase diagram for the
      lipopolymer systems and to assess the amount of lipopolymer that can be loaded
      into DC16PC lipid bilayers before micellization takes place. Unilamellar and
      micellar phase structures are investigated by fluorescence quenching using
      bilayer permeating dithionite. The chain length-dependent critical lipopolymer
      concentration, denoting the lamellar-to-micellar phase transition, compares
      favorably with a theoretical prediction based on free-energy considerations
      involving bilayer cohesion and lateral pressure exerted by the polymer chains.

PMID- 9284317
TI  - Spatial resolution of the variable-period x-ray standing-wave method as applied
      to model membranes.
AB  - A series of model membranes as Langmuir-Blodgett (LB) films composed of long
      chain zinc alkanoates (saturated fatty acid salts) was used to evaluate the
      spatial resolution of the variable-period x-ray standing-wave (XSW) technique.
      The chain length dependence of the zinc mean position (z) above the supporting
      substrate demonstrates that it is possible to detect differences in (z) of 1-2 A.
      Thus 1-2 A is the spatial resolution of the method in the current application.
      The data show that the chain tilt angle is chain length dependent, varying from
      40 degrees to 0 degrees for alkanoates 18 and 24 carbon atoms long, respectively.
      The spread about the mean position of the zinc in the film, sigma(in), was found
      to be independent of chain length at 10.0 A for all members of the series.
      Sigma(in) was shown to be insensitive to the presence of a "spacer" omega
      tricosenoic acid (omegaTA) bilayer placed between the zinc alkanoate LB film and
      the coated gold mirror. However, an overlayer of omegaTA sharpened the zinc ion
      distribution and lowered the chain tilt angle. This study provides important
      information regarding sample composition and constitution that facilitates
      membrane structure determination by XSWs.

PMID- 9284316
TI  - Phosphatidylcholine acyl unsaturation modulates the decrease in interfacial
      elasticity induced by cholesterol.
AB  - The effect of cholesterol on the interfacial elastic packing interactions of
      various molecular species of phosphatidylcholines (PCs) has been investigated by
      using a Langmuir-type film balance and analyzing the elastic area compressibility
      moduli (Cs(-1)) as a function of average cross-sectional molecular area. Emphasis
      was on the high surface pressure regions (pi > or = 30 mN/m) which are thought to
      mimic biomembrane conditions. Increasing levels of cholesterol generally caused
      the in-plane elasticity of the mixed monolayers to decrease. Yet, the magnitude
      of the cholesterol-induced changes was markedly dependent upon PC hydrocarbon
      structure. Among PC species with a saturated sn-1 chain but different sn-2 chain
      cis unsaturation levels [e.g., myristate (14:0), oleate (18:1delta9(c), linoleate
      (18:2delta9,12(c), arachidonate (20:4delta5,8,11,14(c), or docosahexenoate
      (22:6delta4,7,10,13,16,19(c)], the in-plane elasticity moduli of PC species with
      higher sn-2 unsaturation levels were less affected by high cholesterol mol
      fractions (e.g., >30 mol %) than were the more saturated PC species. The largest
      cholesterol-induced decreases in the in-plane elasticity were observed when both
      chains of PC were saturated (e.g., di-14:0 PC). When both acyl chains were
      identically unsaturated, the resulting PCs were 20-25% more elastic in the
      presence of cholesterol than when their sn-1 chains were long and saturated
      (e.g., palmitate). The mixing of cholesterol with PC was found to diminish the in
      plane elasticity of the films beyond what was predicted from the additive
      behavior of the individual lipid components apportioned by mole and area
      fraction. Deviations from additivity were greatest for di-14:0 PC and were least
      for diarachidonoyl PC and didocosahexenoyl PC. In contrast to Cs(-1) analyses,
      sterol-induced area condensations were relatively unresponsive to subtle
      structural differences in the PCs at high surface pressures. Cs(-1) versus
      average area plots also indicated the presence of cholesterol concentration
      dependent, low-pressure (<14 mN/m) phase boundaries that became more prominent as
      PC acyl chain unsaturation increased. Hence, area condensations measured at low
      surface pressures often do not accurately portray which lipid structural features
      are important in the lipid-sterol interactions that occur at high membrane-like
      surface pressures.

PMID- 9284318
TI  - His166 is critical for active-site proton transfer and phototaxis signaling by
      sensory rhodopsin I.
AB  - Photoinduced deprotonation of the retinylidene Schiff base in the sensory
      rhodopsin I transducer (SRI-Htrl) complex results in formation of the phototaxis
      signaling state S373. Here we report identification of a residue, His166,
      critical to this process, as well as to reprotonation of the Schiff base during
      the recovery phase of the SRI photocycle. Each of the residue substitutions A, D,
      G, L, S, V, or Y at position 166 reduces the flash yield of S373, to values
      ranging from 2% of wild type for H166Y to 23% for H166V. The yield of S373 is
      restored to wild-type levels in Htrl-free H166L by alkaline deprotonation of
      Asp76, a Schiff base proton acceptor normally not ionized in the SRI-Htrl
      complex, showing that proton transfer from the Schiff base in H166L occurs when
      an acceptor is made available. The flash yield and rate of decay of S373 of the
      mutants are pH dependent, even when complexed with Htrl, which confers pH
      insensitivity to wild-type SRI, suggesting that partial disruption of the complex
      has occurred. The rates of S373 reprotonation at neutral pH are also prolonged in
      all H166X mutants, with half-times from 5 s to 160 s (wild type, 1 s). All
      mutations of His166 tested disrupt phototaxis signaling. No response (H166D,
      H166L), dramatically reduced responses (H166V), or inverted responses to orange
      light (H166A, H166G, H166S, and H166Y) or to both orange and near-UV light
      (H166Y) are observed. Our conclusions are that His166 1) plays a role in the
      pathways of proton transfer both to and from the Schiff base in the SRI-Htrl
      complex, either as a structurally important residue or possibly as a participant
      in proton transfers; 2) is involved in the modulation of SRI photoreaction
      kinetics by Htrl; and 3) is important in phototaxis signaling. Consistent with
      the involvement of the His imidazole moiety, the addition of 10 mM imidazole to
      membrane suspensions containing H166A receptors accelerates S373 decay 10-fold at
      neutral pH, and a negligible effect is seen on wild-type SRI.

PMID- 9284320
TI  - Comparison of the electrophoretic and hydrodynamic properties of DNA and RNA
      oligonucleotide duplexes.
AB  - The electrophoretic behavior of defined DNA and RNA oligonucleotide duplexes from
      10 to 20 bp in length has been investigated as a function of salt conditions, gel
      concentration, and temperature. The RNA oligomers migrated much more slowly than
      the DNA oligomers of the same sequence under all conditions. From sedimentation
      equilibrium and velocity measurements, the apparent partial specific volume in
      0.1 M KCI, 20 mM NaPi, pH 7, was determined as 0.56 +/- 0.015 ml g(-1) for DNA
      and 0.508 ml g(-1) for RNA. The translational friction coefficients were
      determined and compared with the values calculated for cylinders. Taking into
      account the shape factors, the solution density, and partial specific volumes,
      the effective degree of hydration was estimated as 0.8-1 g g(-1) DNA. There was
      no significant difference in the frictional coefficients of the DNA and RNA
      oligomers, indicating that the effective sizes of DNA and RNA are very similar in
      solution. The differential electrophoretic mobility of DNA and RNA must arise
      from the differences in interaction with counterions, which is probably a global
      property of the oligonucleotides.

PMID- 9284319
TI  - Assessment of intra-SR free [Ca] and buffering in rat heart.
AB  - To measure the free intrasarcoplasmic reticulum [Ca] ([Ca]SR) in isolated rat
      cardiac microsomes, ventricular tissue was homogenized in the presence of the low
      affinity Ca indicator furaptra. Stepwise increases in cuvette [Ca] ([Ca]c) in the
      presence of ATP caused progressive increases in steady-state intravesicular
      fluorescence ratio to a maximum (Rmax). Steady-state [Ca]SR/[Ca]c was
      approximately 7000. Therefore the resting [Ca]SR may approach 700 microM in the
      rat cardiac myocyte at [Ca]c = 100 nM. The sarcoplasmic reticulum (SR) Ca pump
      requires a free energy of deltaG approximately 44 kJ x mol(-1) to generate this
      [Ca] gradient (e.g., approximately 74% of deltaG(ATP)). Total SR 45Ca uptake was
      also measured in digitonin-permeabilized myocytes as a function of [Ca]c in the
      absence of precipitating ions. The steady-state SR Ca content at 100 nM [Ca]c was
      approximately 400 micromol/liter cytosolic volume. Used together, these data
      allowed evaluation of the in situ SR Ca-buffering properties. The SR Ca-binding
      site concentration was approximately 14 mM, and Kd(Ca) approximately 0.638 mM
      [Ca]SR.

PMID- 9284321
TI  - Conformational transitions of the phosphodiester backbone in native DNA: two
      dimensional magic-angle-spinning 31P-NMR of DNA fibers.
AB  - Solid-state 31P-NMR is used to investigate the orientation of the phosphodiester
      backbone in NaDNA-, LiDNA-, MgDNA-, and NaDNA-netropsin fibers. The results for A
      and B-DNA agree with previous interpretations. We verify that the binding of
      netropsin to NaDNA stabilizes the B form, and find that in NaDNA, most of the
      phosphate groups adopt a conformation typical of the A form, although there are
      minor components with phosphate orientations close to the B form. For LiDNA and
      MgDNA samples, on the other hand, we find phosphate conformations that are in
      variance with previous models. These samples display x-ray diffraction patterns
      that correspond to C-DNA. However, we find two distinct phosphate orientations in
      these samples, one resembling that in B-DNA, and one displaying a twist of the
      PO4 groups about the O3-P-O4 bisectors. The latter conformation is not in
      accordance with previous models of C-DNA structure.

PMID- 9284322
TI  - Crystal structure of d(GCGCGCG) with 5'-overhang G residues.
AB  - The crystal structure of the DNA heptamer d(GCGCGCG) has been solved at 1.65 A
      resolution by the molecular replacement method and refined to an R-value of 0.184
      for 3598 reflections. The heptamer forms a Z-DNA d(CGCGCG)2 with 5'-overhang G
      residues instead of an A-DNA d(GCGCGC)2 with 3'-overhang G residues. The overhang
      G residues from parallel strands of two adjacent duplexes form a trans reverse
      Hoogsteen G x G basepair that stacks on the six Z-DNA basepairs to produce a
      pseudocontinuous helix. The reverse Hoogsteen G x G basepair is unusual in that
      the displacement of one G base relative to the other allows them to participate
      in a bifurcated (G1)N2 . . . N7(G8) and an enhanced (G8)C8-H . . . O6(G1)
      hydrogen bond, in addition to the two usual hydrogen bonds. The 5'-overhang G
      residues are anti and C2'-endo while the 3'-terminal G residues are syn and C2'
      endo. The conformations of both G residues are different from the syn/C3'-endo
      for the guanosine in a standard Z-DNA. The two cobalt hexammine ions bind to the
      phosphate groups in both GpC and CpG steps in Z(I) and Z(II) conformations. The
      water structure motif is similar to the other Z-DNA structures.

PMID- 9284323
TI  - How Chlamydomonas keeps track of the light once it has reached the right
      phototactic orientation.
AB  - By using a real-time assay that allows measurement of the phototactic orientation
      of the unicellular alga Chlamydomonas with millisecond time resolution, it can be
      shown that single photons not only induce transient direction changes but that
      fluence rates as low as 1 photon cell(-1) s(-1) can already lead to a persistent
      orientation. Orientation is a binary variable, i.e., in a partially oriented
      population some organisms are fully oriented while the rest are still at random.
      Action spectra reveal that the response to a pulsed stimulus follows the Dartnall
      nomogram for a rhodopsin while the response to a persistent stimulus falls off
      more rapidly toward the red end of the spectrum. Thus light of 540 nm, for which
      chlamy-rhodopsin is equally sensitive as for 440-nm light, induces no measurable
      persistent orientation while 440-nm light does. A model is presented which
      explains not only this behavior, but also how Chlamydomonas can track the light
      direction and switches between a positive and negative phototaxis. According to
      the model the ability to detect the direction of light, to make the right turn
      and to stay oriented, is a direct consequence of the helical path of the
      organism, the orientation of its eyespot relative to the helix-axis, and the
      special shielding properties of eyespot and cell body. The model places
      particular emphasis on the fact that prolonged swimming into the correct
      direction not only requires making a correct turn initially, but also avoiding
      further turns once the right direction has been reached.

PMID- 9284324
TI  - A microspectrophotometric study of the shielding properties of eyespot and cell
      body in Chlamydomonas.
AB  - The eyespot apparatus of the unicellular alga Chlamydomonas exhibits a clear
      directivity, i.e., it perceives light from different directions with different
      sensitivity. Using a newly constructed confocal microscope we have studied how
      absorption and reflection of eyespot and cell body shape this directivity. In
      agreement with previous results the eyespot was found to be highly reflectant,
      owing to its interference reflector design, but only for yellow light. Light of
      490 nm, the maximum of absorption of the photoreceptor, was hardly reflected at
      all, even when the reflector was "tuned" to lower wavelengths by tilting it
      relative to the incoming light. The absorption of the carotenoids in the
      interference reflector also contributed little to the shielding properties of the
      cell, leaving the major contribution to the cell body. Thus most of the
      attenuation of light reaching the eyespot from the rear is due to chlorophyll and
      other pigments within the cell. In its peak around 490 nm the "contrast-ratio"
      reached a value of 8-10.

PMID- 9284325
TI  - Effects of fluorine substitution on the structure and dynamics of complexes of
      dihydrofolate reductase (Escherichia coli).
AB  - Fluorine NMR experiments with a protein containing fluorinated amino acid analogs
      can often be used to probe structure and dynamics of the protein as well as
      conformational changes produced by binding of small molecules. The relevance of
      NMR experiments with fluorine-containing materials to characteristics of the
      corresponding native (nonfluorinated) proteins depends upon the extent to which
      these characteristics are altered by the presence of fluorine. The present work
      uses molecular dynamics simulations to explore the effects of replacement of
      tryptophan by 6-fluorotryptophan in folate and methotrexate complexes of the
      enzyme dihydrofolate reductase (DHFR) (Escherichia coli). Simulations of the
      folate-native enzyme complex produce local correlation times and order parameters
      that are generally in good agreement with experimental values. Simulations of the
      corresponding fluorotryptophan-containing system indicate that the structure and
      dynamics of this complex are scarcely changed by the presence of fluorinated
      amino acids. Calculations with the pharmacologically important methotrexate
      enzyme complex predict dynamical behavior of the protein similar to that of the
      folate complex for both the fluorinated and native enzyme. It thus appears that,
      on the time scale sampled by these computer simulations, substitution of 6
      fluorotryptophan for tryptophan has little effect on either the structures or
      dynamics of DHFR in these complexes.

PMID- 9284328
TI  - Electrorotation of colloidal particles and cells depends on surface charge.
AB  - The importance of surface conductivity to the frequency-dependent polarizability
      and the rotation of particles in circular electric fields (electrorotation) is
      emphasized by various theoretical and experimental investigations. Although
      surface conductivity seems to be naturally related to the ionic double layer,
      there is rare experimental evidence of a direct relationship. To highlight the
      role of surface charges in electrorotation, an apparatus was developed with a
      symmetrical three-electrode arrangement for field frequencies between 25 Hz and
      80 MHz. The three-dimensional electrostatic field distribution between the
      electrodes was evaluated numerically. With this device, rotating, gradient, and
      homogeneous electric fields of defined precision and homogeneity could be applied
      to slightly conducting suspensions. Surface properties of monodisperse latex
      particles (O 9.67 microm), carrying weak acid groups, were characterized by
      suspension conductometric titration. This procedure determined the amount of
      carboxyl groups and showed that strong acid groups were missing on the surface of
      these particles. To obtain the electrophoretic mobility, the spheres were
      separated by free-flow electrophoresis, and the zeta-potential was calculated
      from these data. Single-particle rotation experiments on fractions of specified
      electrophoretic mobility were carried out at frequencies between 25 Hz and 20
      MHz. By analyzing the pH dependence of the rotation velocity, it could be shown
      that the rotation rate is determined by surface charges, both at the peak in
      rotation rate near the Maxwell-Wagner frequency (MWF) and at low frequencies. The
      inversion of the rotation direction at the MWF peak for vanishing surface charges
      was demonstrated. An analytical model for the double layer and dissociation on a
      charged surface was developed that is valid for low and high zeta-potentials.
      This model could provide convincing evidence of the linear dependence of the MWF
      rotation velocity on surface charge.

PMID- 9284326
TI  - Smooth muscle myosin light chain kinase, supramolecular organization, modulation
      of activity, and related conformational changes.
AB  - It has recently been suggested that activation of smooth muscle myosin light
      chain kinase (MLCK) can be modulated by formation of supramolecular structures
      (Sobieszek, A. 1991. Regulation of smooth muscle myosin light chain kinase.
      Allosteric effects and co-operative activation by CaM. J. Mol. Biol. 220:947
      957). The present light scattering data demonstrate that the inactive (calmodulin
      free) MLCK apoenzyme exists in solution as a mixture of oligomeric (2% by
      weight), dimeric (53%), and monomeric (45%) species at physiological ionic
      strength (160 mM salt). These long-living assemblies, the lifetime of which was
      measured by minutes, were in equilibrium with each other. The most likely form of
      the oligomer was a spiral-like hexamer, the dimensions of which fit very well the
      helical structure of self-assembled myosin filaments (Sobieszek, A. 1972. Cross
      bridges on self-assembled smooth muscle myosin filaments. J. Mol. Biol. 70:741
      744). After activation of the kinase by calmodulin (CaM) we could not detect any
      appreciable changes in the distribution of the kinase species either when the
      kinase was saturated with CaM or when its molar concentration exceeded that of
      CaM. Our fluorescent measurements suggest that the earlier observed inhibition of
      kinase at substoichiometric amounts of CaM (Sobieszek, A., A. Strobl, B. Ortner,
      and E. Babiychuk. 1993. Ca2+-calmodulin-dependent modification of smooth-muscle
      myosin light chain kinase leading to its co-operative activation by calmodulin.
      Biochem. J. 295:405-411) is associated with slow conformational change(s) of the
      activated (CaM-bound) kinase molecules. Such conformational rearrangements also
      took place with equimolar kinase to CaM; however, in this case there was no
      decrease in MLCK activity. The nature of these conformational changes, which are
      accompanied by reduction of the kinase for CaM affinity, is discussed.

PMID- 9284327
TI  - Phosphatidylserine liposomes can be tethered by caldesmon to actin filaments.
AB  - Rotary shadowing electron microscopy revealed that attachment of caldesmon to
      phosphatidylserine (PS) liposomes was mainly through its C-terminal end. To
      determine the PS-binding sites of caldesmon, we have made use of synthetic
      peptides covering the two C-terminal calmodulin binding sites and a recombinant
      fragment corresponding to the N-terminal end of the C-terminal domain that
      contains an amphipathic helix. Interactions of these peptides with the PS
      liposomes were studied by nondenaturing gel electrophoresis and fluorescence
      spectroscopy. The results showed that both calmodulin-binding sites of caldesmon
      were able to interact with PS. The affinity (Kd) of PS for these sites was in the
      range of 1.8-14.3 x 10(-5) M, compared to 0.69 x 10(-5) M for the whole caldesmon
      molecule. Fragments located outside of calmodulin-binding sites bound PS weakly
      (3.85 x 10(-4) M) and thus may contain a second class of lipid-binding sites.
      Binding of PS induced conformational changes in regions other than the C-terminal
      PS-binding sites, as evidenced by the changes in the susceptibility to
      proteolytic cleavages. Most significantly, the presence of caldesmon greatly
      increased binding of PS to F-actin, suggesting that caldesmon may tether PS
      liposomes to actin filaments. These results raise the possibility that caldesmon
      lipid interactions could play a functionally important role in the assembly of
      contractile filaments near the membranes.

PMID- 9284329
TI  - Thy-1 immunolabeled thymocyte microdomains studied with the atomic force
      microscope and the electron microscope.
AB  - The atomic force microscope (AFM) and the transmission electron microscope (TEM)
      have been used to study the morphology of isolated mouse thymocyte microdomains
      and Thy-1 antigen distribution at the surface of these structures. AFM images
      were recorded in air in the contact mode on membrane vesicles deposited on
      previously heated tissue culture plastic sheets and indirectly immunolabeled for
      Thy-1 expression with colloidal gold-conjugated secondary antibodies. AFM images
      of untreated plastic plates showed a very characteristic network of streaks 20
      200 nm wide. Heating the plastic removed the streaks and provided flat surfaces
      (r.m.s. 1 nm). This substrate allowed strong adsorption and homogeneous spreading
      of the vesicles and easy manipulations during immunolabeling experiments.
      Vesicles flattened on the substrate without losing their morphology. The 10-nm
      membrane-bound gold beads were reproducibly imaged without degradation by
      repeated tip scanning. The observed microdomains had a mean diameter of 184 +/-
      76 nm, and 65% of them were specifically labeled. Images obtained with the TEM on
      the same vesicles, deposited on carbon-coated grids and negatively stained,
      confirmed the AFM observations. The size distribution of the microdomains was
      quite similar, but the number of beads per vesicle was significantly higher, and
      76% of the vesicles were labeled. The difference may be explained 1) by removal
      of beads from the vesicles in the additional washing step with water, which was
      necessary for the AFM; 2) by tip-sample convolution; and 3) by statistical
      fluctuations.

PMID- 9284330
TI  - The height of biomolecules measured with the atomic force microscope depends on
      electrostatic interactions.
AB  - In biological applications of atomic force microscopy, the different surface
      properties of the biological sample and its support become apparent. Observed
      height differences between the biomolecule and its supporting surface are thus
      not only of structural origin, but also depend on the different sample-tip and
      support-tip interactions. This can result in negative or positive contributions
      to the measured height, effects that are described by the DLVO (Derjaguin,
      Landau, Verwey, Overbeek) theory. Experimental verification shows that the
      electrostatic interactions between tip and sample can strongly influence the
      result obtained. To overcome this problem, pH and electrolyte concentration of
      the buffer solution have to be adjusted to screen out electrostatic forces. Under
      these conditions, the tip comes into direct contact with the surface of support
      and biological system, even when low forces required to prevent sample
      deformation are applied. In this case, the measured height can be related to the
      thickness of the native biological structure. The observed height dependence of
      the macromolecules on electrolyte concentration makes it possible to estimate
      surface charge densities.

PMID- 9284331
TI  - Rapid kinetics of insertion and accessibility of spin-labeled phospholipid
      analogs in lipid membranes: a stopped-flow electron paramagnetic resonance
      approach.
AB  - Spin-labeled phospholipid analogs have been employed to probe the transbilayer
      distribution of endogenous phospholipids in various membrane systems. To
      determine the transmembrane distribution of the spin-labeled analogs, the analogs
      are usually inserted into the membrane of interest and subsequently the amount of
      analog in the outer membrane leaflet is determined either by chemical reduction
      with ascorbate or by back-exchange to bovine serum albumin (BSA). For accurate
      determination of the transbilayer distribution of analogs, both the kinetics of
      incorporation and those of accessibility of analogs to ascorbate or BSA have to
      be fast in comparison to their transbilayer movement. By means of stopped-flow
      electron paramagnetic resonance (EPR) spectroscopy, we have studied the kinetics
      of incorporation of the spin-labeled phosphatidylcholine (PC) analog 1-palmitoyl
      2-(4-doxylpentanoyl)-sn-glycero-3-phosphocholine (SL-PC) and of its accessibility
      to chemical reduction and to back-exchange at room temperature. Incorporation of
      SL-PC into the outer leaflet of egg phosphatidylcholine (EPC) and red cell ghost
      membranes was essentially completed within 5 s. Ninety percent of the SL-PC
      molecules located in the outer membrane leaflet of those membranes were extracted
      by BSA within 15 s. All exterior-facing SL-PC molecules were reduced by ascorbate
      in a pseudo-first-order reaction within 60 s in EPC membranes and within 90 s in
      red cell ghost membranes. The rate of the reduction process could be enhanced by
      approximately 30-fold when 6-O-phenyl-ascorbic acid was used instead of ascorbate
      as the reducing agent. The results are discussed in light of assaying rapid
      transbilayer movement of spin-labeled analogs in biological membranes.

PMID- 9284332
TI  - Glutamatergically induced pattern of Ca2+ driving potential as a mechanism of
      postsynaptic plasticity.
AB  - Simulation studies were performed in a model of neuronal dendrite with Na+ and K+
      channels and with ionotropic and metabotropic glutamate receptors. The ionotropic
      receptors were either N-methyl-D-aspartate (NMDA)-sensitive, voltage-dependent,
      and permeable to Ca2+, Na+, and K+, or non-NMDA-sensitive, voltage-independent,
      and permeable to Na+ and K+. The metabotropic receptors provided a catalytic
      effect on Ca2+-induced Ca2+ release from intracellular stores. Local
      intracellular concentration [Ca2+]i in the cytoplasm was changed because of
      exchange with the stores, axial diffusion, and transmembrane inward passive and
      outward pump fluxes. Tonic activation of ionotropic and metabotropic receptors in
      a particular range of intensities triggered the formation of spatially periodic
      [Ca2+]i hot and cold bands arising from an initial uniform state. The period and
      width of the bands were smaller at higher levels of tonic NMDA activation and
      higher metabotropically controlled rates of Ca2+-induced Ca2+ release. The
      bandwidths also depended on the dendrite diameter, the specific membrane, and
      cytoplasm resistivity. This activity-induced pattern led to long-term, spatially
      inhomogeneous change in local excitatory postsynaptic potentials (EPSPs) of NMDA
      synapses phasically activated with the same presynaptic intensity. The phasic
      EPSPs were potentiated if the synapse occurred in the hot band.

PMID- 9284333
TI  - Cochlear outer hair cell bending in an external electric field.
AB  - We have used a high-resolution motion analysis system to reinvestigate shape
      changes in isolated guinea pig cochlear outer hair cells (OHCs) evoked by low
      frequency (2-3 Hz) external electric stimulation. This phenomenon of
      electromotility is presumed to result from voltage-dependent structural changes
      in the lateral plasma membrane of the OHC. In addition to well-known longitudinal
      movements, OHCs were found to display bending movements when the alternating
      external electric field gradients were oriented perpendicular to the cylindrical
      cell body. The peak-to-peak amplitude of the bending movement was found to be as
      large as 0.7 microm. The specific sulfhydryl reagents, p
      chloromercuriphenylsulfonic acid and p-hydroxymercuriphenylsulfonic acid, that
      suppress electrically evoked longitudinal OHCs movements, also inhibit the
      bending movements, indicating that these two movements share the same underlying
      mechanism. The OHC bending is likely to result from an electrical charge
      separation that produces depolarization of the lateral plasma membrane on one
      side of the cell and hyperpolarization on the other side. In the cochlea, OHC
      bending could produce radial distortions in the sensory epithelium and influence
      the micromechanics of the organ of Corti.

PMID- 9284335
TI  - An improved fit to Website osmotic pressure data.

PMID- 9284336
TI  - Transplant of polymer-encapsulated cells genetically engineered to release nerve
      growth factor allows a normal functional development of the visual cortex in dark
      reared rats.
AB  - Visual experience is necessary for the normal development of the visual system.
      Dark-reared mammals show abnormal vision when reintroduced into a normal
      environment. The absence of visual experience during the critical period results
      in reduced and/or inappropriate neural responses in visual cortical neurons. The
      change in electrical activity induced by dark rearing is probably reflected by
      the modulation of specific unknown molecules. Neurotrophins are present in the
      developing visual cortex and their production depends on visually driven
      electrical activity. Recent findings support the possibility that an important
      link between electrical activity in the visual pathway and correct development of
      visual properties is represented by neurotrophins. We advance the hypothesis that
      the visual abnormalities present in dark-reared animals could be due to a
      decreased production of a neurotrophin secondary to the lack of visual
      stimulation. We report that some properties of visual cortical response such as
      receptive field size, orientation selectivity, adaptation to repeated
      stimulation, response latency and visual acuity are virtually normal in dark
      reared rats transplanted with polymer-encapsulated baby hamster kidney cells
      genetically engineered to release nerve growth factor.

PMID- 9284334
TI  - Effects of extracellular calcium on electrical bursting and intracellular and
      luminal calcium oscillations in insulin secreting pancreatic beta-cells.
AB  - The extracellular calcium concentration has interesting effects on bursting of
      pancreatic beta-cells. The mechanism underlying the extracellular Ca2+ effect is
      not well understood. By incorporating a low-threshold transient inward current to
      the store-operated bursting model of Chay, this paper elucidates the role of the
      extracellular Ca2+ concentration in influencing electrical activity,
      intracellular Ca2+ concentration, and the luminal Ca2+ concentration in the
      intracellular Ca2+ store. The possibility that this inward current is a carbachol
      sensitive and TTX-insensitive Na+ current discovered by others is discussed. In
      addition, this paper explains how these three variables respond when various
      pharmacological agents are applied to the store-operated model.

PMID- 9284337
TI  - Synaptic beta-amyloid precursor proteins increase with learning capacity in rats.
AB  - The precursor proteins of Alzheimer's disease beta-amyloid peptide, the beta
      amyloid precursor protein isoforms, comprise a family of neuronal proteins with
      synaptic localization whose physiological roles in brain are poorly understood.
      One possible role for synaptic proteins is involvement in neuronal plasticity.
      After exposure to an enriched environment compared to impoverished conditions,
      rats exhibited superior cognitive capacity. Up to approximately four-fold
      increased overall levels of beta-amyloid precursor proteins were found in
      cortical/subcortical tissue of the enriched animals displaying significantly more
      synapses immunoreactive for the different beta-amyloid precursor protein isoforms
      (beta-amyloid precursor protein695- and beta-amyloid precursor protein751/770) in
      hippocampus and adjacent occipital cortex. This correlation thus provides in vivo
      evidence for an association of beta-amyloid precursor proteins with plastic
      changes induced by complex environment with consequences for cognitive functions
      and suggests that impaired beta-amyloid precursor protein metabolism at synapses
      might contribute to brain dysfunction in Alzheimer's disease.

PMID- 9284338
TI  - Detailed mapping of the histamine H2 receptor and its gene transcripts in guinea
      pig brain.
AB  - Autoradiographic studies of the distribution of the histamine H2 receptor and its
      messenger RNAs were performed on serial frontal and a few sagittal sections of
      guinea-pig brain using [(125)I]iodoaminopotentidine for radioligand binding and a
      33P-labelled complementary RNA probe for in situ hybridization, respectively.
      Both probes were validated by assessing non-specific labelling using non
      radioactive competing H2 receptor ligands and a sense probe for binding sites and
      gene transcripts, respectively. In some areas, e.g., cerebral cortex, hippocampal
      complex or cerebellum, such studies were completed by identification of neurons
      expressing the H2 receptor messenger RNAs on emulsion-dipped sections. Nissl
      stained sections from comparable levels were used to localize brain structures.
      In many brain areas, the distribution of the H2 receptor and its messenger RNAs
      appeared to parallel that known for histaminergic axons. For instance. high
      levels of both H2 receptor markers were detected in striatal and limbic areas
      known to receive abundant histaminergic projections. In contrast, in septum,
      hypothalamic, pontine and several thalamic nuclei, a comparatively low density of
      both H2 receptor markers was detected, suggesting that histamine actions in these
      areas are mediated by H1 and/or H3 receptors. Generally, the distribution of H2
      receptor messenger RNA correlates well with that of [(125)I]iodoaminopotentidine
      binding sites, although some differences were observed. In a few regions (e.g.,
      substantia nigra, locus coeruleus) high or moderate densities of binding sites
      were accompanied by a much more restricted expression of H2 receptor transcripts.
      Conversely, the mammillary region and the pontine nucleus exhibited higher levels
      of hybridization than of binding sites. In hippocampus, cerebral and cerebellar
      cortex there was a selective localization of the H2 receptor messenger RNA in the
      granule cells of dentate gyrus, pyramidal cells of the Ammon's horn and cerebral
      cortex, and Purkinje cells of cerebellum, whereas [(125)I]iodoaminopotentidine
      binding sites were located in layers where the dendritic trees of these messenger
      RNA-expressing neurons extend. The same discrepancy between messenger RNAs and
      binding sites suggests that striatonigral endings are endowed with the H2
      receptor. The histamine H1 and H2 receptors both appear to be present in several
      brain areas, in some cases in a way suggesting their potential co-expression by
      the same neuronal populations, e.g., in granule and pyramidal cells in the
      hippocampal formation. This co-expression accounts for synergic responses, e.g.,
      on cAMP generation, previously observed upon co-stimulation of both receptor
      subtypes. The widespread distribution of the H2 receptor, namely in thalamic
      nuclei or in telencephalic areas such as most layers of the cerebral cortex,
      together with its excitatory role previously established in electrophysiological
      studies, support its alleged function in mediating the histamine-driven control
      of arousal mechanisms. In addition, the detection of H2 receptor expression in
      brainstem areas from which other monoaminergic pathways involved in the control
      of states of sleep and wakefulness emanate, e.g., several raphe nuclei, locus
      coeruleus or substantia innominata, suggests possible interrelationships between
      all of these systems with highly divergent projections to the thalamus and
      telencephalon. The present mapping of the H2 receptor and its gene transcripts
      should facilitate neurochemical, neurophysiological and behavioural studies aimed
      at clarifying the role of histaminergic systems in brain.

PMID- 9284339
TI  - An immunocytochemical study on the distribution of two G-protein-gated inward
      rectifier potassium channels (GIRK2 and GIRK4) in the adult rat brain.
AB  - G-protein-gated inward rectifier potassium channels mediate the synaptic actions
      of numerous neurotransmitters in the mammalian brain, and were recently shown to
      be candidates for genetic mutations leading to neuronal cell death. This report
      describes the localization of G-protein-gated inward rectifier potassium channel
      2 and G-protein-gated inward rectifier potassium channel-4 proteins in the rat
      brain, as assessed by immunocytochemistry. G-protein-gated inward rectifier
      potassium channel-2 immunoreactivity was widely distributed throughout the brain,
      with the strongest staining seen in the hippocampus, septum, granule cell layer
      of the cerebellum, amygdala and substantia nigra pars compacta. In contrast, G
      protein-gated inward rectifier potassium channel-4 immunoreactivity was
      restricted to some neuronal populations, such as Purkinje cells and neurons of
      the globus pallidus and the ventral pallidum. The presence of G-protein-gated
      inward rectifier potassium channel-2 immunoreactivity in substantia nigra pars
      compacta dopaminergic neurons was confirmed by showing its co-localization with
      tyrosine hydroxylase by double immunocytochemistry, and also by selectively
      lesioning dopaminergic neurons with the neurotoxin 6-hydroxydopamine. At the
      cellular level both proteins were localized in neuronal cell bodies and
      dendrites, but clear differences were seen in the degree of dendritic staining
      among neuronal groups. For some neuronal groups the staining of distal dendrites
      (notably dendritic spines) was strong, while for others the cell body and
      proximal dendrites were preferentially labelled. In addition, some of the results
      suggest that G-protein-gated inward rectifier potassium channel-2 protein could
      be localized in distal axonal terminal fields. A knowledge of the distribution of
      G-protein-gated inward rectifier potassium channel proteins in the brain could
      help to elucidate their physiological roles and to evaluate their potential
      involvement in neurodegenerative processes in animal models and human diseases.

PMID- 9284340
TI  - Quantitative analysis of cuneocerebellar projections in rats: differential
      topography in the anterior and posterior lobes.
AB  - The distribution of wheatgerm agglutinin-horseradish peroxidase-labelled mossy
      fibre terminals of internal and external cuneate projections to the cerebellar
      anterior and posterior lobes were quantitatively analysed in adult rats. Computer
      based image analysis mapped the spatial distribution of labelled cuneocerebellar
      terminals in two-dimensional reconstructions of the unfolded cortex.
      Cuneocerebellar projections are mainly ipsilateral in their distribution. Cuneate
      projections to the anterior lobe vermis-medial paravermis terminate in well
      circumscribed, irregularly-shaped patches. These terminal patches are aligned and
      form a longitudinally continuous, parasagittally oriented stripe in the lateral
      vermis-medial paravermis of lobules I-V. These terminal patches represent the
      topographically organized divergent projections of different parts of the
      internal and external cuneate nuclei. Cuneocerebellar projections to the lateral
      paravermis-hemisphere, particularly in the posterior part of lobule V, are
      organized as a transversely oriented band of terminals. Cuneocerebellar
      projections to the posterior lobe terminate mainly in three transversely oriented
      bands of terminals located at the junction between lobules. An anterior band of
      terminals was located in lobule VI anteriorly and was continuous with the band of
      terminals located in the posterolateral part of lobule V at the junction of these
      two lobules. Intermediate and posterior transversely oriented bands of terminals
      were located at the VII-VIII and VIII-IX junctions, respectively. Cuneocerebellar
      projections to these three bands largely appear to represent convergent
      projections from different parts of the cuneate nuclei. These findings are
      discussed in relation to similarly analysed and previously reported findings on
      the organization of lower thoracic-upper lumbar spinocerebellar projections and
      in the context of how cuneocerebellar somatosensory input may be differentially
      organized and processed in disparate areas of the cerebellar cortex.

PMID- 9284341
TI  - Quantitative analysis of converging spinal and cuneate mossy fibre afferent
      projections to the rat cerebellar anterior lobe.
AB  - The convergence/divergence of mossy fibre afferent projections to the cerebellar
      anterior lobe from a single lumbar segment, from adjacent or widely separated
      lower thoracic and lumbar segments, and finally from the lower thoracic-upper
      lumbar spinal cord and the brainstem cuneate nuclei was quantitatively analysed
      in adult rats. Spinal and cuneate mossy fibre terminals were differentially
      labelled with biotinylated dextran amine and cholera toxin subunit B,
      immunohistochemically identified in the same histological sections, and their
      spatial distributions quantitatively plotted in computer reconstructions of the
      unfolded anterior lobe cortex. Afferent convergence was quantified by calculating
      the number of biotinylated dextran amine-labelled terminals that radially
      overlapped with cholera toxin-labelled terminals at points on the unfolded
      cortical map that represented theoretical Purkinje cells. Spino- and
      cuneocerebellar mossy fibre terminals are organized in patches that are oriented
      in parasagittally-oriented stripes or transversely oriented bands. Afferent
      convergence was greatest following biotinylated dextran amine and cholera toxin
      injections in the same or adjacent spinal lumbar segments (60 and 52%,
      respectively). When biotinylated dextran amine and cholera toxin were injected in
      a single segment differentially labelled terminals appeared randomly intermingled
      in common patches. There was a trend for terminals labelled from adjacent lumbar
      segments to be more segregated in the patches. Segmentally separated biotinylated
      dextran amine and cholera toxin spinal cord injections (four lumbar segments)
      resulted in clearly segregated (80%) biotinylated dextran amine from cholera
      toxin-labelled terminal patches or patches with distinct divergence of the
      differentially labelled terminals in the patch. Cuneocerebellar terminals
      labelled with biotinylated dextran amine were located in patches, stripes, and
      bands spatially segregated from terminal patches, stripes, and bands of cholera
      toxin-labelled spinal afferents except at their immediate borders where some
      radial overlap occurred (9-22%). These anatomical findings for a fractured
      somatotopy of spinal and cuneate inputs to the cerebellar anterior lobe
      complement neurophysiological findings for a very similar pattern of organization
      of cutaneous inputs to the posterior lobe, and are discussed in light of
      potential mechanisms for anterior lobe processing of somatosensory information.

PMID- 9284342
TI  - Effects of cholinergic denervation on seizure development and neurotrophin
      messenger RNA regulation in rapid hippocampal kindling.
AB  - Intraventricular 192 IgG-saporin was used to induce a selective lesion of basal
      forebrain cholinergic neurons in rats. When subjected to 40 rapid hippocampal
      kindling stimulations with 5-min intervals, these animals exhibited increased
      number of generalized seizures and a higher mean seizure grade in response to the
      first five stimulations, and required fewer stimuli to develop focal behavioural
      seizures, as compared to non-lesioned rats. In contrast, both groups showed
      similarly enhanced responsiveness when test stimulated four weeks later. Using in
      situ hybridization, cholinergic denervation was found to cause a significant
      decrease of basal brain-derived neurotrophic factor messenger RNA levels in the
      hippocampal formation and piriform cortex, whereas gene expression for nerve
      growth factor, neurotrophin-3, and TrkB and TrkC was unchanged. Four weeks after
      rapid kindling stimulations, basal levels of brain-derived neurotrophic factor
      messenger RNA in the dentate granule cells were restored to normal in the
      lesioned rats, whereas neurotrophin-3 messenger RNA levels were decreased. No
      differences in the seizure-evoked levels of neurotrophin and Trk messenger RNAs
      were detected, except in the dentate granule cell layer, which had significantly
      higher brain-derived neurotrophic factor messenger RNA expression in the lesioned
      animals at 2 h. In conclusion, the basal forebrain cholinergic system (i) dampens
      the severity of recurring seizures induced by rapid hippocampal kindling
      stimulations, but has no effect on the subsequent delayed phase of
      epileptogenesis; and (ii) exerts a tonic stimulation of basal brain-derived
      neurotrophic factor messenger RNA levels in the hippocampal formation and
      piriform cortex. The findings also indicate that the cholinergic lesion does not
      affect neurotrophin and Trk gene expression after recurring seizures, and that
      the kindling process leads to long-term changes in basal brain-derived
      neurotrophic factor and neurotrophin-3 messenger RNA levels in the denervated
      animals.

PMID- 9284343
TI  - Cholinergic deafferentation exacerbates seizure-induced loss of somatostatin
      immunoreactive neurons in the rat hippocampus.
AB  - The loss of somatostatin-immunoreactive neurons and the sprouting of mossy fibers
      are typical histopathological abnormalities in the hippocampus in experimental
      and human temporal lobe epilepsy. To investigate whether the development of
      seizure-induced alterations is regulated by the subcortical afferent pathways to
      the hippocampus, we lesioned cholinergic, noradrenergic or serotonergic afferent
      pathways in rats two days after seizures were induced with kainate. Two months
      later, somatostatin-immunoreactive neurons were counted in the hilus to assess
      the severity of neuronal damage. Mossy fiber sprouting was analysed from adjacent
      Timm-stained sections. Kainate-induced seizures caused a loss of hilar
      somatostatin-immunoreactive neurons in the septal end of the hippocampus, where
      63% of the somatostatin-immunoreactive neurons survived. Even more severe damage
      was found in the temporal end of the hippocampus (only 21% surviving).
      Cholinergic deafferentation of the hippocampus (using 192-IgG saporin) decreased
      the overall number of hilar somatostatin-immunoreactive neurons. In control rats
      that did not receive kainate, 87% (septal end) and 74% (temporal end) of the
      hilar somatostatin-immunoreactive neurons remained after cholinergic
      deafferentation. Moreover, seizure-induced damage to hilar somatostatin
      immunoreactive neurons was further exacerbated by 192-IgG-saporin, with only 35%
      of the neurons remaining in the septal end and 14% in the temporal end of the
      hippocampus. Noradrenergic [using N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine]
      or serotonergic (using 5,7-dihydroxytryptamine) lesions did not affect the number
      of hilar somatostatin-immunoreactive neurons either in control or in kainate
      treated rats. The severity and distribution of seizure-induced mossy fiber
      sprouting were also not affected by any of the lesions. These data suggest that
      various subcortical afferent pathways may differentially modulate seizure-induced
      damage to the hippocampus. Damage to cholinergic neurons results in the loss of
      hilar somatostatin-immunoreactive neurons and exacerbates the seizure-induced
      loss of somatostatin-immunoreactive neurons.

PMID- 9284344
TI  - Cholinergic denervation and sympathetic ingrowth result in persistent changes in
      hippocampal muscarinic receptors.
AB  - Our laboratory has been utilizing the model of hippocampal sympathetic ingrowth,
      which has been suggested to occur in Alzheimer's disease, to investigate the
      effects of cholinergic denervation and hippocampal rearrangements. After
      cholinergic denervation by medial septal lesions, peripheral sympathetic fibres
      originating from the superior cervical ganglia grow into the rat hippocampus.
      This hippocampal sympathetic ingrowth can be prevented by superior cervical
      ganglionectomy. We examined the long-term effects of these treatments on
      muscarinic receptors by comparing [3H]quinuclidinyl benzilate binding in rat
      dorsal hippocampus four and 12 weeks post lesion. Four groups of animals were
      employed, including controls (sham lesion+sham ganglionectomy), animals with
      ingrowth (medial septal lesion+ sham ganglionectomy), animals with cholinergic
      denervation alone (medial septal lesion+ ganglionectomy), and ganglionectomy
      alone (sham lesion+ganglionectomy) animals. In dorsal hippocampus four weeks post
      lesion, binding affinity was similar among all groups, while muscarinic receptor
      number was increased in ingrowth animals as compared to both the control
      (P<0.0002) and ganglionectomy animals (P<0.01). By 12 weeks, receptor affinity
      was significantly decreased in ingrowth (P<0.0001) and cholinergic denervation
      (P<0.0003) groups, and receptor number remained significantly elevated in
      ingrowth animals as compared to control (P<0.01), ganglionectomy (P<0.02) and
      cholinergic denervation (P<0.01) groups. The decrease in muscarinic receptor
      affinity may provide some insight into the ineffectiveness of cholinomimetic
      therapies in Alzheimer's disease, in that agonist efficacy would be reduced at
      the receptor.

PMID- 9284345
TI  - Elevated basal trough levels of corticosterone suppress hippocampal 5
      hydroxytryptamine(1A) receptor expression in adrenally intact rats: implication
      for the pathogenesis of depression.
AB  - Several studies with adrenalectomized rats have shown that the suppressive
      effects of exogenous corticosteroids on 5-hydroxytryptamine(1A) receptor function
      are mediated by the high-affinity mineralocorticoid receptor, rather than the
      lower affinity glucocorticoid receptor. In the present study, adrenally intact
      rats were subcutaneously implanted for six days with pellets containing a small
      amount of corticosterone, which leads to a flattening of the circadian rhythm in
      the level of circulating hormone. The peak in daily corticosterone is suppressed,
      the basal trough is increased, and the hormone levels remain at a constant value
      equivalent to the daily average of about 5 microg/dl, which is usually observed
      in rats. Accordingly, this regime of corticosterone treatment did not enhance
      exclusively glucocorticoid receptor-controlled parameters, such as the weight of
      the thymus. Effects involving mineralocorticoid receptor activation were
      enhanced, since reductions were observed in stress-induced plasma corticosterone
      levels and adrenal weight. 5-Hydroxytryptamine(1A) receptor messenger RNA levels
      were found to be suppressed by approximately 25% in the dentate gyrus of the
      hippocampus of these corticosterone pellet-implanted rats. This suppression was
      reflected in significantly reduced [3H]8-hydroxy-2-(di-n-propylamino)tetralin
      binding in the hippocampal region. We propose therefore that this suppressive
      effect on 5-hydroxytryptamine(1A) receptor expression involves enhanced
      occupation of mineralocorticoid receptors, under a condition of elevated basal
      trough corticosteroid levels as is commonly observed in human depression.

PMID- 9284346
TI  - Lesion-induced proliferation of neuronal progenitors in the dentate gyrus of the
      adult rat.
AB  - In order to determine whether granule cell death stimulates the proliferation of
      granule cell precursors in the dentate gyrus of the adult rat, we performed both
      excitotoxic and mechanical lesions of the granule cell layer and examined the
      numbers of proliferating cells at different survival times. Using [3H]thymidine
      autoradiography, bromodeoxyuridine labelling and proliferating cell nuclear
      antigen immunohistochemistry, we observed an increase in proliferating cells on
      the lesioned side compared to the unlesioned side 24 h after surgery. A
      significant positive correlation between the extent of granule cell damage and
      the number of proliferating cells was observed. Combined [3H]thymidine
      autoradiography and immunohistochemistry for cell-specific markers revealed that
      the vast majority of proliferating cells had the morphological characteristics of
      granule cell precursors and were not immunoreactive for vimentin, a marker of
      immature glia. Combined [3H]thymidine autoradiography and terminal
      deoxynucleotidyl transferase-mediated dUTP nick end-labelling for degenerating
      cells showed that the proliferating cells did not rapidly degenerate. Three weeks
      after the lesion, most cells produced in response to the lesion had the
      morphological characteristics of mature granule neurons, were located in the
      granule cell layer and expressed markers of mature granule neurons, including
      neuron-specific enolase, the N-methyl-D-aspartate receptor subunit NRI and
      calbindin. These findings suggest that granule cell death stimulates the
      proliferation of precursor cells, many of which survive and differentiate into
      mature granule neurons.

PMID- 9284347
TI  - Soluble macrophage factors trigger apoptosis in cultured hippocampal neurons.
AB  - It is not clear whether macrophages which can phagocytose dead cells, may also
      contribute to death of potentially viable neurons when they enter brain lesion
      sites after insult. We have initially examined the effects of macrophage
      conditioned medium on the integrity of hippocampal neurons in culture. We
      assessed qualitative and quantitative changes in neuronal status in terms of
      nuclear morphology, internucleosomal cleavage, cell membrane integrity and
      process density. Cell morphology with manual counts to quantitate findings showed
      that macrophage conditioned medium significantly increased the percentage of
      neurons with abnormal nuclei. Aurintricarboxylic acid attenuated this effect.
      Demonstration of laddering of DNA on agarose gels suggested an apoptosis-like
      event. A commercially available kit used to detect high concentrations of 3'-OH
      DNA ends showed marked increase in labelled cells. These combined findings
      confirmed that apoptosis was the main event triggered by conditioned medium.
      Although the number of cells with incompetent membranes also increased with
      conditioned medium application the majority of cells with apoptotic nuclei
      maintained membrane integrity. Conditioned medium also resulted in significant
      loss of cell processes. Conditioned medium from stimulated microglia showed a
      similar pattern of injury. The response of stressed neurons to conditioned medium
      was also tested. Exposure of cultures to mild hypoxia resulted in injury but did
      not significantly alter their subsequent vulnerability to macrophage-conditioned
      medium. Early experiments suggest that the documented changes in neuronal status
      are caused by relatively large and stable secreted macrophage proteins.

PMID- 9284348
TI  - Radiation-induced apoptosis in developing rats and kainic acid-induced
      excitotoxicity in adult rats are associated with distinctive morphological and
      biochemical c-Jun/AP-1 (N) expression.
AB  - Ionizing radiation produces apoptosis in the developing rat brain. Strong c-Jun
      immunoreactivity, as revealed with the antibody c-Jun/AP-1 (N) which is raised
      against the amino acids 91-105 mapping with the amino terminal domain of mouse c
      Jun p39, is simultaneously observed in the nucleus and cytoplasm of apoptotic
      cells. Western blotting of total brain homogenates, using the same antibody,
      shows a p39 band in control rats which is accompanied by a strong, phosphorylated
      p62 double-band in irradiated animals. In addition, increased c-Jun N-terminal
      kinase 1 expression, as found on western blots, is found in irradiated rats when
      compared with controls. Intraperitoneal injection of kainic acid at convulsant
      doses to the adult rat produces cell death with morphological features of
      necrosis, together with the appearance of cells with fine granular chromatin
      degeneration and small numbers of apoptotic-like cells, in the entorhinal and
      piriform cortices, basal amygdala, certain thalamic nuclei, and CA1 region of the
      hippocampus. c-Jun expression in kainic acid-treated rats, as revealed with the c
      Jun/AP-1 (N) antibody, is found in the nuclei of a minority of cells in the same
      areas. The vast majority of c-Jun-immunoreactive cells have normal nuclear
      morphology, whereas necrotic cells are negative and only a few cells with fine
      granular chromatin condensation and apoptotic cells following kainic acid
      injection are stained with c-Jun antibodies. Western blotting, using the same
      antibody, shows a p39 band in control rats, which is accompanied by a band at
      about p26 from 6 h onwards following kainic acid injection. Decreased c-Jun N
      terminal kinase 1 expression, as revealed on western blots, is observed in kainic
      acid-treated rats. These results show that the antibody c-Jun/AP-1 (N) recognizes
      three different forms of c-Jun-related immunoreactivity in normal and
      pathological states, which are associated with the different outcome of cells.
      These results stress the necessity of examining in detail the composition of c
      Jun-immunoreactive bands and the metabolic state of c-Jun(s) in different
      paradigms of cell death and survival.

PMID- 9284349
TI  - Infraorbital nerve transection and whisker follicle removal in adult rats affect
      microglia and astrocytes in the trigeminal brainstem. A study with lipocortin1-
      and S100beta-immunohistochemistry.
AB  - Transections of the infraorbital nerve in adult rats resulted in progressive
      alterations of microglia identified by Lipocortinl immunoreactivity at the sites
      where the primary afferents terminate, i.e. in the trigeminal brainstem sensory
      nuclei. Microglia proliferated three- to four-fold. Their cell bodies enlarged
      and their processes thickened. Microglial responses were similar to the removal
      of whisker follicles. However, they were restricted to discrete nuclear
      subregions that matched with the known whisker somatotopy. Astrocytes identified
      by S100beta immunoreactivity showed minor increases in size and in population
      density. No microglial or astrocytic reactions were found in the second and third
      synaptic relays of the somatosensory pathway. Because both types of lesion
      reportedly lead to the reorganization of primary afferents, our results establish
      the two experimental designs as valuable tools to elucidate the role of microglia
      and Lipocortin1 in adult brain plasticity.

PMID- 9284351
TI  - P19 cells differentiate into glutamatergic and glutamate-responsive neurons in
      vitro.
AB  - The neurotransmitter L-glutamate has been associated with a number of
      developmental events within the central nervous system including synaptogenesis
      and the refinement of topographically ordered neural maps. As a model for
      studying such events at the molecular level, we have examined the expression of
      glutamate and glutamate receptors in neurons that develop from P19 cells in
      response to retinoids. We report here that many P19-derived neurons do contain
      glutamate in secretory vesicles and that this glutamate appears to function as a
      neurotransmitter. The neurotransmitter GABA is also present in these cultures and
      both glutamate and GABA appeared to co-localize in some neuronal processes. Both
      neurotransmitters were released from the neurons in response to membrane
      depolarization. These neurons also express various glutamate receptor subunits
      including GluR1, GluR4 and NMDAR1 as detected by immunological methods. Using
      whole-cell patch-clamping, we have recorded spontaneous postsynaptic potentials
      which increase in both amplitude and frequency with time in culture and which are
      sensitive to the glutamate antagonist kynurenic acid Thus, P19-derived neurons
      mature in culture and form electrically active neural networks involving
      glutamate and glutamate receptors.

PMID- 9284350
TI  - Opiate receptors modulate estrogen-induced cholecystokinin and tachykinin but not
      enkephalin messenger RNA levels in the limbic system and hypothalamus.
AB  - Cholecystokinin, substance P and methionine enkephalin all regulate the display
      of reproductive behaviour. Their expression is exquisitely regulated by estrogen
      in the limbic-hypothalamic circuit, a circuit that regulates the display of
      estrogen-sensitive female reproductive behavior. Relatively little is known,
      however, about the interaction of endogenous opioid peptides with cholecystokinin
      and substance P in the limbic-hypothalamic circuit. Opiates antagonize the
      release of cholecystokinin and substance P in the hypothalamus and periaqueductal
      gray and stimulate cholecystokinin messenger RNA levels in the amygdala. To
      determine the effect of endogenous opioid input on estrogen-induced
      cholecystokinin, enkephalin and substance P expression, in situ hybridization
      histochemistry was used to examine estrogen-induced messenger RNA levels of these
      neuropeptides in specific nuclei of the limbic system and hypothalamus in the
      presence of opiate receptor antagonists. Estrogen treatment of ovariectomized
      rats significantly elevated cholecystokinin messenger RNA levels in the central
      portion of the medial preoptic nucleus, the encapsulated portion of the bed
      nucleus of the stria terminalis and the posterodorsal medial amygdala, as well as
      increased preproenkephalin and preprotachykinin messenger RNA levels in the
      ventromedial hypothalamic nucleus and the posterodorsal medial amygdala. The
      universal opiate receptor antagonist naltrexone and the delta-opiate receptor
      antagonist naltrindole each potentiated the estrogen-induced increase and
      elevated cholecystokinin messenger RNA levels an additional 1.9- to 2.8-fold
      depending on the nucleus examined, but had no effect on the estrogen-induced
      expression of either preproenkephalin or preprotachykinin messenger RNA. beta
      Funaltrexamine, a mu-opiate receptor antagonist, had no effect on the medial
      preoptic or medial amygdaloid cholecystokinin messenger RNA levels or on the
      estrogen-induced expression of preproenkephalin messenger RNA but did cause a
      decrease in estrogen-induced cholecystokinin messenger RNA levels in the bed
      nucleus of the stria terminalis and a decrease in the preprotachykinin messenger
      RNA levels in the ventromedial hypothalamic nucleus. These results indicate that
      endogenous opioids, acting on the delta-opiate receptor within nuclei of the
      limbic-hypothalamic circuit, restrain the estrogen-induced increase of
      cholecystokinin messenger RNA expression. Activation of the mu-opiate receptor,
      however, may facilitate cholecystokinin messenger RNA expression in the bed
      nucleus of the stria terminalis and preprotachykinin messenger RNA expression in
      the ventromedial hypothalamic nucleus. Thus, endogenous opioid peptides may act
      in a site- and receptor-specific manner to modulate estrogen-induced neuropeptide
      levels in the limbic system and hypothalamus.

PMID- 9284352
TI  - Identification and characterization of a novel gene (neurorep 1) expressed in
      nerve cells and up-regulated after axotomy.
AB  - A novel gene, designated neurorep 1, was isolated by differential hybridization
      screening from a complementary DNA library constructed from the rat facial
      nucleus whose nerve had been transected seven days before sampling. In situ
      hybridization revealed that this gene was up-regulated in the repair stage after
      axotomy. The deduced protein, Neurorep 1, consists of 293 amino acid residues,
      and its molecular mass is approximately 34,000. Protein sequence motif search
      indicates that this protein has an ecto-5'-nucleotidase consensus sequence at the
      carboxyl terminal region. In vitro studies showed that Neurorep 1 significantly
      increased the activity of ecto-5'-nucleotidase, which is considered to be
      involved in regeneration and repair of the central nervous system. Neurorep 1
      might play a significant role in the repair process of nerve tissues by its
      regulation of ecto-5'-nucleotidase activity.

PMID- 9284353
TI  - Modulation of excitatory synaptic transmission in locus coeruleus by multiple
      presynaptic metabotropic glutamate receptors.
AB  - Metabotropic glutamate receptors have been implicated in modulation of synaptic
      transmission in many different systems. This study reports the effects of
      selective activation of metabotropic glutamate receptors on synaptic transmission
      in intracellularly recorded locus coeruleus neurons in brain slice preparations.
      Perfusion of either L-2-amino-4-phosphonobutyric acid (L-AP4; 0.1-500 microM) or
      (+/-)-1-aminocyclopentane-trans-1,3,dicarboxylic acid (t-ACPD; 0.1-500 microM)
      caused a depression of excitatory postsynaptic potentials in a dose-dependent
      fashion to about 70% inhibition. Both agonists exerted their effects at
      relatively low concentrations with estimated EC50s of 2.6 microM and 11.5 microM
      for L-AP4 and t-ACPD, respectively. This inhibition was not observed with the
      potent group I metabotropic glutamate receptor agonist (RS)-3,5
      dihydroxyphenylglycine (DHPG; 100 microM). Conversely, (R)-4-carboxy-3
      hydroxyphenyl-glycine (4C-3H-PG), a group I antagonist/group II agonist, and
      2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (APDC), a novel and specific group II
      agonist, also caused an inhibition of excitatory postsynaptic potentials. Both t
      ACPD and L-AP4 produced an increase in paired-pulse facilitation, and failed to
      change the locus coeruleus response to focally applied glutamate, indicating a
      presynaptic locus of action. The L-AP4 inhibition was antagonized by (S)-amino-2
      methyl-4-phosphonobutanoic acid (MAP4: group III antagonist) but not by (RS)
      alpha-methyl-4-carboxyphenylglycine [(RS)-MCPG; mixed antagonist], suggesting
      that this agonist acts through a type 4 metabotropic glutamate receptor.
      Conversely, t-ACPD was antagonized by MCPG and by ethyl glutamate (group II
      antagonist), but not by aminoindan dicarboxylic acid (AIDA; group I antagonist)
      or MAP4, suggesting that this agonist acts on a type 2 or 3 metabotropic
      glutamate receptor. Taken together, these results suggest that two
      pharmacologically distinct presynaptic metabotropic glutamate receptors function
      in an additive fashion to inhibit excitatory synaptic transmission in locus
      coeruleus neurons. These receptors may be involved in a feedback mechanism and as
      such may function as autoreceptors for excitatory amino acids.

PMID- 9284354
TI  - Position of the ventral pallidum in the rat prefrontal cortex-basal ganglia
      circuit.
AB  - The ventral pallidum receives major inputs from the nucleus accumbens, a striatal
      region related to the prefrontal cortex. The ventral pallidum, through its
      projections to the mediodorsal nucleus of the thalamus, has been considered as
      the main output structure of the prefrontal-basal ganglia circuits. However, as
      shown recently, the ventral pallidum also sends efferents to the subthalamic
      nucleus and the substantia nigra, suggesting that it could participate in
      intrinsic basal ganglia circuits. The aim of the present investigation was to
      determine the position of the ventral pallidum in the prefrontal-basal ganglia
      circuit originating from the prelimbic and medial orbital areas. Following
      injections of biocytin (an anterograde tracer) into the region of the core of the
      nucleus accumbens receiving excitatory inputs from the prelimbic and medial
      orbital areas, axonal terminal fields were observed in a delineated dorsal region
      of the ventral pallidum. When the biocytin injections were made into this ventral
      pallidal region, anterogradely labelled fibres were observed in both the
      dorsomedial substantia nigra pars reticulata and the medial subthalamic nucleus,
      but not in the mediodorsal nucleus of the thalamus. Confirming these anatomical
      observations, electrical stimulation of the core of the nucleus accumbens induced
      an inhibition of the spontaneous activity (D=34.9+/-13.3 ms, L=9.2+/-3.3 ms) in
      46.5% of the ventral pallidal cells. Among these responding cells, 43% were
      antidromically driven from the subthalamic nucleus, 30% from the substantia nigra
      pars reticulata and only 6% from the mediodorsal nucleus of the thalamus. These
      data demonstrate that the region of the ventral pallidum involved in the
      prefrontal cortex-basal ganglia circuit originating from the prelimbic and medial
      orbital areas represents essentially a ventral subcommissural extension of the
      external segment of the globus pallidus since it exhibits similar extrinsic
      connections and functional characteristics. In conclusion, in this prelimbic and
      medial orbital channel, the ventral pallidum cannot be considered as a major
      output structure but is essentially involved in intrinsic basal ganglia circuits.

PMID- 9284355
TI  - Involvement of pallidal and nigral GABA mechanisms in the generation of tremulous
      jaw movements in rats.
AB  - Four experiments were conducted to investigate the role of pallidal and nigral
      GABA in the generation of tremulous jaw movements in rats. In these experiments,
      tremulous jaw movements were induced by i.p. injections of the anticholinesterase
      tacrine (5.0 mg/kg). Previous work has shown that the tremulous jaw movements
      induced by cholinomimetics and dopamine depletion are dependent upon striatal
      mechanisms. Thus, the present study investigated potential striatal output
      pathways that could be involved in the generation of these movements. Because
      there are GABAergic projections from neostriatum to entopeduncular nucleus
      (medial globus pallidus) and substantia nigra pars reticulata, the GABA agonist
      muscimol was injected directly into these structures to study the effects of GABA
      stimulation on tacrine-induced jaw movements. Injections of muscimol into the
      entopeduncular nucleus (25-100 ng) failed to have any significant effects on
      tacrine-induced vacuous jaw movements. However, injections of muscimol (12.5-50
      ng) into the substantia nigra pars reticulata blocked the jaw movements induced
      by tacrine. In the third experiment, it was again demonstrated that 25.0 ng of
      muscimol injected directly into the substantia nigra pars reticulata blocked the
      jaw movements induced by tacrine; in addition, it was shown that injections of
      this dose 2.0 mm dorsal to the substantia nigra pars reticulata failed to affect
      tacrine-induced tremulous jaw movements. It was shown in the fourth experiment
      that injections of muscimol into a more medial portion of the substantia nigra
      pars reticulata also reduced tacrine-induced tremulous jaw movements. These
      results indicate that stimulation of GABA(A) receptors in substantia nigra pars
      reticulata can block tacrine-induced tremulous jaw movements. This finding is
      consistent with the notion that striatonigral GABA projections are involved in
      the generation of tremulous jaw movements. It is also possible that striatonigral
      GABA mechanisms are involved in human clinical phenomena such as parkinsonian
      tremor.

PMID- 9284356
TI  - Electrophysiological and immunocytochemical characterization of GABA and dopamine
      neurons in the substantia nigra of the rat.
AB  - Neurons in the substantia nigra pars reticulata and pars compacta of the rat were
      studied using a combination of intracellular electrophysiological recording in in
      vitro and subsequent immunocytochemical double and triple labelling techniques.
      The neurons recorded in the pars reticulata were identified as either GABA or
      dopamine neurons: neurons were considered to be GABA neurons if they were
      immunopositive for glutamate decarboxylase, whereas those neurons which were
      immunopositive for tyrosine hydroxylase were considered to be dopaminergic. The
      GABA neurons had short duration action potentials (0.45+/-0.03 ms halfwidth), no
      apparent rectifying currents, no low threshold calcium spikes, were spontaneously
      active (7.4+/-3.7 Hz), and could maintain high firing rates. The dopamine neurons
      had long duration action potentials (1.49+/-0.10 ms), displayed both anomalous
      inward and transient outward rectifying currents, and more than half (12/17
      neurons) displayed a low threshold calcium spike. Their spontaneous firing rate
      was lower than that of the GABA neurons (2.3+/-1.0 Hz), and they displayed strong
      frequency adaptation. Morphological reconstruction of neurobiotin-filled neurons
      revealed that the pars reticulata GABA neurons had more extensive local dendritic
      arborization than the dopamine neurons from either the pars reticulata or the
      pars compacta. All of the neurons recorded from the pars compacta were dopamine
      neurons; they were found not to be different either electrophysiologically or
      morphologically from pars reticulata dopamine neurons. The electrophysiology of
      the GABA neurons suggests that input activity is translated linearly to spike
      frequency. These GABA neurons probably represent the projection neurons of the
      pars reticulata, and it is thus likely that this basal ganglia output is
      frequency coded. The close similarity between the dopamine neurons in the pars
      compacta, which give rise to the nigrostriatal pathway, and those in the pars
      reticulata supports the notion that the dopamine neurons in these two regions are
      part of the same neuronal population.

PMID- 9284357
TI  - Evidence for serotonin sensitivity of adult rat spinal axons: studies using
      randomized double pulse stimulation.
AB  - We have recently shown both inhibitory and excitatory effects of serotonin on
      neonatal rat dorsal column axons. While neonatal rat dorsal column axons also
      respond to norepinephrine and GABA, adult rat dorsal columns are insensitive to
      the actions of both compounds. Therefore, we studied the effects of serotonin
      agonists on adult rat dorsal column axons using randomized double pulse stimuli
      at 0.2 Hz with random interpulse intervals of 3, 4, 5, 8, 10, 20, 30, 50 and 80
      ms. The serotonin(1A) agonist, 8-hydroxy-dipropylaminotetralin-hydrobromide (8-OH
      DPAT), significantly modulated test response amplitudes at 3, 4, 5 and 8 ms
      interpulse intervals by 29.6+/-4.0%, 17.4+/-2.1%, 9.6+/-2.3%, and 12.4+/-2.2% of
      conditioning pulse amplitudes, respectively. The mean latencies at 3, 4 and 5 ms
      interpulse intervals increased by 17.0+/-5.1%, 8.6+/-2.1%, and 5.1+/-1.4%,
      respectively (P<0.05). However, neither 10 microM 8-OH-DPAT nor 100 microM
      serotonin hydrochloride affected the compound action potentials evoked by
      conditioning or test pulses. In contrast, treatment with 100 microM quipazine
      dimaleate (a serotonin(2A) agonist) decreased the refractory period. While the
      response amplitudes to a 3-ms double pulse were reduced by 11.0+/-1.5% during the
      control period, the test response fell to only 2.4+/-1.8% of the conditioning
      response amplitudes after exposure to 100 microM quipazine. 8-OH-DPAT decreased
      the amplitude, prolonged the latency and increased the refractory periods of
      compound action potentials in the adult rat dorsal column, although a high
      concentration of the agonist (100 microM) was required for these effects. In
      contrast, the serotonin(2A) agonist, quipazine, decreased refractory periods.
      These results suggest that both serotonin(1A) and serotonin(2A) receptor subtypes
      are present on adult spinal dorsal column axons. Further, these receptors have
      opposing effects on axonal excitability, despite the fact that their
      sensitivities are relatively low.

PMID- 9284358
TI  - The role of afferent inputs to supraoptic nucleus oxytocin neurons during
      naloxone-precipitated morphine withdrawal in the rat.
AB  - During prolonged exposure to morphine, oxytocin neurons of the rat supraoptic
      nucleus develop dependence, shown by hyperexcitation following morphine
      withdrawal. The present study investigated the role of afferent projections to
      the supraoptic nucleus in this withdrawal excitation. Rats were made morphine
      dependent by continuous intracerebroventricular infusion of morphine at
      increasing doses (up to 50 microg/h). On the sixth day, rats were anaesthetized
      with pentobarbitone and morphine withdrawal was precipitated by intraperitoneal
      injection of naloxone (5 mg/kg). Fos-immunoreactivity in the supraoptic nucleus,
      and also in the median preoptic nucleus, organum vasculosum of the lamina
      terminalis and subfornical organ, which project to the supraoptic nucleus,
      increased following morphine withdrawal. However, retrograde tracing from the
      supraoptic nucleus showed that, of the neurons in these regions which project to
      the supraoptic nucleus, only 0.4-7.1% expressed Fos in response to morphine
      withdrawal. Following morphine withdrawal, Fos-immunoreactivity was present in
      39.2% and 19.8% of the tyrosine hydroxylase-immunoreactive neurons of the A1/C1
      and A2/C2 cell groups. Of the cells in these regions identified as projecting to
      the supraoptic nucleus, 11.3% in the region of the A2 cell group and 12.7% in the
      region of the A1 cell group expressed Fos after morphine withdrawal. In a second
      study, monoamine release was measured in the supraoptic nucleus of urethane
      anaesthetized morphine-dependent and -naive rats. Retrodialysis of naloxone (10[
      5] M) into the supraoptic nucleus induced a small increase in plasma oxytocin
      concentration in morphine-dependent rats (13.5+/-4.8 pg/ml increase) but not in
      naive rats (1.2+/-5.9 pg/ml decrease), with no significant change in monoamine
      release in either morphine-dependent or -naive rats. Intravenous injection of
      naloxone (5 mg/kg) 1 h later produced a further significant increase in plasma
      oxytocin concentration in morphine-dependent rats concomitant with a significant
      increase in noradrenaline release from the supraoptic nucleus. Thus, morphine
      withdrawal excitation of supraoptic oxytocin neurons occurs concurrently with a
      modestly increased activity of their input from the brainstem, and very little
      activation in other known inputs.

PMID- 9284359
TI  - [Met]enkephalin in the spinal cord is involved in the antinociception induced by
      intracerebroventricularly-administered etorphine in the mouse.
AB  - We have recently reported that the antinociception induced by etorphine given
      i.c.v. is mediated in part by the stimulation of both mu- and epsilon-opioid
      receptors and the activation of both monoaminergic and opioidergic descending
      pain control systems. [Xu J. Y. et al. (1992) J. Pharmac. exp. Ther. 263, 246
      252]. Since the opioid epsilon-receptor-mediated antinociception induced by beta
      endorphin is mediated by the release of [Met]enkephalin and subsequent
      stimulation of delta-opioid receptors in the spinal cord, the present studies
      were designed to determine if beta-endorphin-like action is also involved in
      etorphine-induced antinociception. The tail-flick test was used to assess the
      antinociceptive response performed in male ICR mice. Etorphine at doses from 5 to
      20 ng given i.c.v. produced a dose-dependent inhibition of the tail-flick
      response. The inhibition of the tail-flick response induced by etorphine given
      i.c.v. was antagonized by intrathecal pretreatment for 60 min with antiserum
      against [Met]enkephalin (10 microg), but not with antiserum against
      [Leu]enkephalin (10 microg) or dynorphin A (1-13) (10 microg). Desensitization of
      delta-opioid receptors in the spinal cord by intrathecal pretreatment with
      [Met]enkephalin (5 microg) for 60 min attenuated i.c.v. administered etorphine
      induced tail-flick inhibition. However, intrathecal pretreatment with
      [Leu]enkephalin (5 microg) or dynorphin A (1-17) (0.1 microg) for 60 min did not
      attenuate i.c.v. administered etorphine-induced tail-flick inhibition. The
      results indicate that antinociception induced by etorphine given i.c.v. is
      mediated in part by the stimulation of the epsilon-opioid receptor at the
      supraspinal sites and by the release of [Met]enkephalin, which subsequently
      stimulates delta-opioid receptors in the spinal cord.

PMID- 9284360
TI  - Evidence for a periaqueductal gray-nucleus retroambiguus-spinal cord pathway in
      the rat.
AB  - The nucleus retroambiguus in the cat has been shown to receive strong projections
      from the periaqueductal gray and to send fibres to distinct motoneuronal cell
      groups in brainstem and spinal cord. The nucleus retroambiguus plays a role in
      the production of vocalization and possibly copulatory (lordosis and mounting)
      behaviour. The question arises of whether a periaqueductal gray nucleus
      retroambiguus-spinal cord projection also exists in the rat. In the present
      study, using the retrograde wheatgerm agglutinin-horseradish peroxidase tracing
      technique, the nucleus retroambiguus was defined as the area in the caudal
      medulla oblongata (1.0-2.0 mm caudal to the obex) which sends its fibres mainly
      through the contralateral spinal cord. Further retrograde tracing experiments
      demonstrated that a relatively large number of neurons in the lateral and ventral
      periaqueductal gray and immediately adjacent tegmentum projects to the caudal
      medullary lateral tegmentum. Anterograde wheatgerm agglutinin-horseradish
      peroxidase tracing studies finally showed that neurons in the lateral
      periaqueductal gray and immediately adjoining tegmentum project specifically to
      the nucleus retroambiguus and not to the lateral tegmentum in general, which
      seems to be the case for the neurons in the ventral periaqueductal gray. The
      results indicate that in the rat a periaqueductal gray nucleus retroambiguus
      spinal cord projection also exists, which may be of crucial importance for the
      study of the anatomical and physiological framework of respiration, vocalization,
      and female and male reproductive behaviour in this animal.

PMID- 9284361
TI  - The contribution of supraspinal, peripheral and intrinsic spinal circuits to the
      pattern and magnitude of Fos-like immunoreactivity in the lumbar spinal cord of
      the rat withdrawing from morphine.
AB  - Withdrawal from morphine evokes increases in Fos-like immunoreactivity in the
      spinal cord, particularly in the superficial dorsal horn, laminae I/II. To
      determine the origin of the increased Fos-like immunoreactivity, we selectively
      targeted central or peripheral opioid receptors with naloxone-methiodide, an
      antagonist that does not cross the blood-brain barrier, or induced withdrawal
      after eliminating possible sources of input to the superficial dorsal horn. To
      induce tolerance, we implanted rats with morphine or placebo pellets (75 mg, six
      pellets over three days). On day 4, withdrawal was precipitated and after 1 h,
      the rats were killed, their spinal cords removed and 50 microm transverse
      sections of the spinal cord immunoreacted with a rabbit polyclonal antiserum
      directed against the Fos protein. In placebo-pelleted rats, none of the different
      procedures, viz. spinal transection, unilateral dorsal rhizotomy (L4-S2),
      neonatal capsaicin treatment or direct intrathecal opioid antagonist injection,
      induced expression of the Fos protein. However, both spinally transected and
      rhizotomized withdrawing animals showed significant increases in Fos-like
      immunoreactivity in laminae I/II, compared to intact withdrawing rats. Neonatal
      treatment with capsaicin, which eliminates C-fibres, did not alter Fos-like
      immunoreactivity. Selective withdrawal of morphine from peripheral opioid
      receptors by naloxone-methiodide did not induce Fos-like immunoreactivity in the
      lumbar spinal cord greater than that recorded in nonwithdrawing rats. However,
      intrathecal injection of naloxone-methiodide increased Fos-like immunoreactivity
      in laminae I/II and the ventral horn to a greater extent than did subcutaneous
      injection of naloxone. We hypothesize that the increased Fos expression after
      systemic withdrawal in spinally-transected rats results from a loss of descending
      inhibitory control that is activated during withdrawal. The increase in
      withdrawal-induced Fos-like immunoreactivity after rhizotomy may be secondary to
      loss of inhibitory controls exerted by large diameter primary afferents or to
      deafferentation-induced reorganization in the dorsal horn. Since capsaicin did
      not alter the magnitude of Fos-like immunoreactivity in withdrawing rats, we
      conclude that hyperactivity of opioid receptor-laden C-fibres is not a necessary
      contributor to the withdrawal-induced increase in Fos-like immunoreactivity in
      laminae I and II. Taken together with the results recorded after intrathecal
      injection of naloxone-methiodide in tolerant rats, we conclude that the pattern
      of lumbar spinal cord Fos expression following systemic withdrawal is primarily a
      consequence of increased activity in opioid receptor-containing circuits
      intrinsic to the dorsal horn and that the magnitude of Fos expression is normally
      dampened by supraspinal and primary afferent-derived inhibitory inputs.

PMID- 9284362
TI  - Dystrophin and its isoforms in a sympathetic ganglion of normal and dystrophic
      mdx mice: immunolocalization by electron microscopy and biochemical
      characterization.
AB  - In normal mouse superior cervical ganglion, dystrophin immunoreactivity is
      present in ganglionic neurons, satellite cells and Schwann cells. It is
      associated with several cytoplasmic organelles and specialized plasma membrane
      domains, including two types of structurally and functionally different
      intercellular junctions: synapses, where it is located at postsynaptic densities,
      and adherens junctions. Dystrophin immunostaining can be ascribed to the 427,000
      mol. wt full-length dystrophin, as well as to the several dystrophin isoforms
      present in superior cervical ganglion, as revealed by western immunoblots. In mdx
      mouse superior cervical ganglion, which lacks the 427,000 mol. wt dystrophin, the
      unchanged pattern of dystrophin immunolabelling observed at several subcellular
      structures indicates the presence of dystrophin isoforms at these sites.
      Moreover, the absence of labelled adherens junctions indicates the presence of
      full-length dystrophin at this type of junction in the normal mouse superior
      cervical ganglion. The lower number of immunopositive postsynaptic densities in
      mdx mouse superior cervical ganglion than in normal mouse ganglion suggests the
      presence, in the latter, of postsynaptic densities with differently organized
      dystrophin cytoskeleton: some containing dystrophin isoforms alone or together
      with 427,000 mol. wt dystrophin, and others containing 427,000 mol. wt dystrophin
      alone.

PMID- 9284363
TI  - Tachykinin NK1 and NK2 receptors mediate non-adrenergic non-cholinergic
      excitatory neuromuscular transmission in the guinea-pig stomach.
AB  - By using selective tachykinin NK1 and NK2 receptor antagonists and agonists, we
      studied the excitatory non-adrenergic non-cholinergic transmission to the
      circular muscle of the corpus of guinea-pig stomach by the sucrose-gap method.
      After elimination of inhibitory junction potentials by apamin (0.1 microM), L
      nitroarginine (30 microM) and tetraethylammonium (10 mM), electrical field
      stimulation (10 Hz) in the presence of atropine (1 microM) and nifedipine (1
      microM) evoked a pure excitatory junction potential and contraction. The
      selective tachykinin NK2 receptor antagonist, MEN 11420, concentration
      dependently inhibited the non-adrenergic non-cholinergic excitatory junction
      potential (EC50=0.09 microM) and contraction (EC50=0.04 microM) evoked by
      electrical field stimulation. On the other hand, the selective NK1 receptor
      antagonist GR 82334 (3 microM) only slightly (by about 30%) inhibited the
      excitatory junction potential while leaving the contraction unaffected. The
      combined administration of GR 82334 (1 microM) and MEN 11420 (0.3 microM)
      produced an additive inhibition of the excitatoryjunction potential,
      significantly larger than that produced by each antagonist alone. In the presence
      of both GR 82334 (1 microM) and MEN 11420 (0.3 microM), the P2 purinoreceptor
      antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (30 microM)
      remarkably inhibited the fast component of the excitatory junction potential. In
      the presence of atropine (1 microM), indomethacin (3 microM) and guanethidine (3
      microM) either the selective NK2 receptor agonist, [betaAla8]neurokinin A (4-10)
      (0.01 microM), or the selective NK1 receptor agonist, [Sar9]substance P sulfone
      (0.3 microM), produced tetrodotoxin-(1 microM) and nifedipine-(1 microM)
      resistant depolarization and contraction. The [Sar9]substance P sulfone (0.3
      microM)-induced contraction, but not that induced by [betaAla8]neurokinin A (4
      10) (0.01 microM), was potentiated by apamin (0.1 microM) plus L-nitroarginine
      (30 microM). In the presence of atropine (1 microM), indomethacin (3 microM),
      guanethidine (3 microM), apamin (0.1 microM) and L-nitroarginine (30 microM), the
      selective tachykinin NK2 and NK1 receptor agonists, [betaAla8]neurokinin A (4-10)
      and [Sar9]substance P sulfone, both produced a concentration-dependent
      depolarization and contraction of the circular muscle. MEN 11420 inhibited the
      responses to [[Ala8]neurokinin A (4-10) without affecting the responses to
      [Sar9]substance P sulfone, while GR 82334 inhibited the responses to
      [Sar9]substance P sulfone but not that to [betaAla8]neurokinin A (4-10). These
      data provide evidence that tachykinin NK2 receptors predominantly mediate the non
      adrenergic non-cholinergic excitatory transmission to the circular muscle of the
      corpus of guinea-pig stomach. In addition, after blocking the non-adrenergic non
      cholinergic inhibitory junction potential by apamin, L-nitroarginine and
      tetraethylammonium, the fast component of the non-adrenergic non-cholinergic
      excitatory junction potential could be mediated by adenosine triphosphate.

PMID- 9284364
TI  - ATP acting on P2Y receptors triggers calcium mobilization in Schwann cells at the
      neuroelectrocyte junction in skate.
AB  - Schwann cells are integral cellular components of the dense cholinergic
      presynaptic plexus (nerve plate) which innervates each electrocyte in skate
      electric organ. Using the Ca2+-sensitive dye fura-2, we have followed the
      response in these cells to various chemical challenges. In K+ depolarized nerve
      plates nerve terminals consistently responded with a rapid and sustained Ca2+
      signal. Schwann cell responses to depolarization were rarely seen but, when
      observed, were always delayed in onset when compared to nerve terminal response
      (6-10 s later). The possibility that these responses were triggered by mediators
      released from nerve terminals was tested by direct application of candidate
      substances. Schwann cells were found to respond to adenosine triphosphate and
      adenosine diphosphate with a biphasic increase of intracellular Ca2+
      concentration, a rapid peak response being followed in the majority of cells by a
      sustained plateau phase. In the absence of external Ca2+ only the transient peak
      response was observed. Depletion of internal Ca2+ stores with thapsigargin
      completely inhibited the adenosine triphosphate-stimulated rise in Schwann cell
      Ca2+. The response to adenosine triphosphate was concentration-dependent (EC50
      2.8 microM) and was reversibly blocked by two antagonists of P2 purinoceptors:
      suramin and reactive blue 2. Adenosine diphosphate and 2-methylthio-adenosine
      triphosphate were equipotent with adenosine triphosphate and at high
      concentrations (100 microM) diadenosine tetraphosphate produced responses
      comparable to low concentrations of adenosine triphosphate. Adenosine, adenosine
      monophosphate, the alpha beta-methylene analogues of adenosine triphosphate and
      adenosine diphosphate, uridine triphosphate, cytidine triphosphate and guanosine
      triphosphate were without significant effect. These results show that, in skate
      electric organ Schwann cells, the release of Ca2+ from intracellular stores is
      triggered by adenosine triphosphate acting on P(2gamma) receptors and suggest
      that Schwann cells may be targets for synaptically-released adenosine
      triphosphate in the electric organ model of the neuromuscular junction.

PMID- 9284365
TI  - Reciprocal connections between the preglomerular nucleus and the central
      posterior/prepacemaker nucleus in the diencephalon of weakly electric fish,
      Apteronotus leptorhynchus.
AB  - The central posterior/prepacemaker nucleus of gymnotiform fish is a bilateral
      cell group located in the dorsal thalamus. This complex consists of approximately
      10,000 neurons which can be divided into several subpopulations. One
      subpopulation comprised of a few hundreds of neurons projects to the pacemaker
      nucleus in the medulla oblongata, thus constituting the prepacemaker nucleus
      portion of this complex. By employing in vitro tract-tracing techniques, we have,
      in the present investigation, examined the pattern of connectivity formed by the
      central posterior/prepacemaker nucleus with a diencephalic cell group, the
      preglomerular nucleus. As demonstrated by anterograde and retrograde tracing, a
      subpopulation of several hundreds of neurons located in the central
      posterior/prepacemaker nucleus project to the ipsi- and contralateral
      preglomerular nucleus. Double-labelling experiments revealed that at least a
      fraction of these neurons also innervate the pacemaker nucleus. In the
      preglomerular nucleus, a large number of neurons give rise to projections that
      terminate in the ipsilateral central posterior/prepacemaker nucleus. The
      reciprocal connection between the central posterior/prepacemaker nucleus and the
      preglomerular nucleus may be used to relay sensory information directly conveyed
      to one of the two nuclei indirectly to the other nucleus. The existence of at
      least some central posterior/prepacemaker nucleus neurons projecting to both the
      preglomerular nucleus and the pacemaker nucleus may provide the morphological
      basis for the transmission of an efference copy of electromotor information
      produced by neurons in the central posterior/prepacemaker nucleus to the
      preglomerular nucleus.

PMID- 9284367
TI  - Interaction of tryptamine and ergoline compounds with threonine 196 in the ligand
      binding site of the 5-hydroxytryptamine6 receptor.
AB  - We examined the ligand-binding site of the 5-hydroxytryptamine6 (5-HT6) receptor
      using site-directed mutagenesis. Interactions with residues in two characteristic
      positions of trans-membrane region V are important for ligand binding in several
      bioamine receptors. In the 5-HT6 receptor, one of these residues is a threonine
      (Thr196), whereas in most other mammalian 5-HT receptors, the corresponding
      residue is alanine. After transient expression in human embryonic kidney 293
      cells, we determined the effects of the mutation T196A on [3H]d-lysergic acid
      diethylamide (LSD) binding and adenylyl cyclase stimulation. This mutation
      produced a receptor with a 10-fold reduced affinity for [3H]LSD and a 6-fold
      reduced affinity for 5-HT. The potency of both LSD and 5-HT for stimulation of
      adenylyl cyclase was also reduced by 18- and 7-fold, respectively. The affinity
      of other N1-unsubstituted ergolines (e.g., ergotamine, lisuride) was reduced 10
      30 fold, whereas the affinity of N1-methylated ergolines (e.g., metergoline,
      methysergide, mesulergine) and other ligands, such as methiothepine, clozapine,
      ritanserin, amitriptyline, and mainserin, changed very little or increased. This
      indicates that in wild-type 5-HT6 receptor, Thr196 interacts with the N1 of N1
      unsubstituted ergolines and tryptamines, probably forming a hydrogen bond. Based
      on molecular modeling, a serine residue in transmembrane region IV of the 5-HT2A
      receptor has previously been proposed to interact with the N1-position of 5-HT.
      When the corresponding residue of the 5-HT6 receptor (Ala154) was converted to
      serine, no change in the affinity of twelve 5-HT6 receptor ligands or in the
      potency of 5-HT and LSD could be detected, suggesting that this position does not
      contribute to the ligand binding site of the 5-HT6 receptor.

PMID- 9284369
TI  - Recombination in HIV: an important viral evolutionary strategy.
AB  - Human immunodeficiency virus (HIV) is a diploid virus: each virion carries two
      complete RNA genomic strands. Homologous recombination can occur when a cell is
      coinfected with two different but related strains. Naturally occurring
      recombinant HIV strains have been found in infected patients in regions of the
      world where multiple genotypic variants cocirculate. One recombinant HIV strain
      has spread rapidly to millions of persons in Southeast Asia. Recombination is a
      mechanism whereby high level and multidrug-resistant strains may be generated in
      individual treated patients. Recombination also poses theoretical problems for
      the development of a safe HIV vaccine. Certain features of HIV replication, such
      as syncytium formation and transactivation, may be best understood as components
      of a sexual reproductive cycle. Recombination may be an important HIV
      evolutionary strategy.

PMID- 9284371
TI  - Resistance, remission, and qualitative differences in HIV chemotherapy.
AB  - To understand the role of qualitative differences in multidrug chemotherapy for
      human immunodeficiency virus (HIV) infection in virus remission and drug
      resistance, we designed a mathematical system that models HIV multidrug
      chemotherapy including uninfected CD4+ T cells, infected CD4+ T cells, and virus
      populations. The model, which includes the latent and progressive stages of the
      disease and introduces chemotherapy, is a system of differential equations
      describing the interaction of two distinct classes of HIV (drug-sensitive [wild
      type] and drug-resistant [mutant]) with lymphocytes in the peripheral blood; the
      external lymphoid system contributes to the viral load. The simulations indicate
      that to preclude resistance, antiviral drugs must be strong enough and act fast
      enough to drive the viral population below a threshold level. The threshold
      depends upon the capacity of the virus to mutate to strains resistant to the
      drugs. Above the threshold, mutant strains rapidly replace wild-type strains.
      Below the threshold, resistant strains do not become established, and remission
      occurs. An important distinction between resistance and remission is the
      reduction of viral production in the external lymphoid system. Also the virus
      population rapidly rebounds when treatment is stopped even after extended periods
      of remission.

PMID- 9284370
TI  - Host genes and HIV: the role of the chemokine receptor gene CCR5 and its allele.
AB  - Since the late 1970s, 8.4 million people worldwide, including 1.7 million
      children, have died of AIDS, and an estimated 22 million people are infected with
      human immunodeficiency virus (HIV)(1). During 1995 and 1996, major clinical and
      laboratory discoveries regarding HIV pathogenesis provided new hope for the
      prevention and treatment of HIV infection. One major discovery was that members
      of the chemokine receptor family serve as cofactors for HIV entry into cells. We
      describe the role of allelic polymorphism in the gene coding for the CCR5
      chemokine receptor with regard to susceptibility to and disease course of HIV
      infection. We also examine the effect of this discovery on medical and public
      health practices.

PMID- 9284372
TI  - Emerging foodborne diseases.
AB  - The epidemiology of foodborne diseases is rapidly changing. Recently described
      pathogens, such as Escherichia coli O157:H7 and the epidemic strain of Salmonella
      serotype Typhimurium Definitive Type 104 (which is resistant to at least five
      antimicrobial drugs), have become important public health problems. Well
      recognized pathogens, such as Salmonella serotype Enteritidis, have increased in
      prevalence or become associated with new vehicles. Emergence in foodborne
      diseases is driven by the same forces as emergence in other infectious diseases:
      changes in demographic characteristics, human behavior, industry, and technology;
      the shift toward a global economy; microbial adaptation; and the breakdown in the
      public health infrastructure. Addressing emerging foodborne diseases will require
      more sensitive and rapid surveillance, enhanced methods of laboratory
      identification and subtyping, and effective prevention and control.

PMID- 9284373
TI  - DDT, global strategies, and a malaria control crisis in South America.
AB  - Malaria is reemerging in endemic-disease countries of South America. We examined
      the rate of real growth in annual parasite indexes (API) by adjusting APIs for
      all years to the annual blood examination rate of 1965 for each country. The
      standardized APIs calculated for Brazil, Peru, Guyana, and for 18 other malaria
      endemic countries of the Americas presented a consistent pattern of low rates up
      through the late 1970s, followed by geometric growth in malaria incidence in
      subsequent years. True growth in malaria incidence corresponds temporally with
      changes in global strategies for malaria control. Underlying the concordance of
      these events is a causal link between decreased spraying of homes with DDT and
      increased malaria; two regression models defining this link showed statistically
      significant negative relationships between APIs and house-spray rates. Separate
      analyses of data from 1993 to 1995 showed that countries that have recently
      discontinued their spray programs are reporting large increases in malaria
      incidence. Ecuador, which has increased use of DDT since 1993, is the only
      country reporting a large reduction (61%) in malaria rates since 1993. DDT use
      for malaria control and application of the Global Malaria Control Strategy to the
      Americas should be subjects of urgent national and international debate. We
      discuss the recent actions to ban DDT, the health costs of such a ban,
      perspectives on DDT use in agriculture versus malaria control, and costs versus
      benefits of DDT and alternative insecticides.

PMID- 9284374
TI  - Emerging and reemerging helminthiases and the public health of China.
AB  - Despite great strides in their control throughout the People's Republic of China,
      helminth infections remain an important public health problem. The Institute of
      Parasitic Diseases of the Chinese Academy of Preventive Medicine, under the
      guidance of the Chinese Ministry of Health, completed a nationwide survey of more
      than 1 million people that showed the high prevalence and intensity of intestinal
      nematode infections; prevalence can sometimes exceed 50% in the Yangtze River
      valley provinces. Schistosoma japonicum is also a major cause of illness in this
      region. Attempts to control Chinese helminthic diseases with conventional
      anthelminthic drugs have been partially thwarted by high posttreatment rates of
      reinfection. Recently, several new human trematode pathogens have been
      identified. Novel approaches to chemoprophylaxis and vaccination may alleviate
      the public health problem caused by Chinese helminths. However, recombinant
      helminth vaccine development will depend on first cataloguing the extensive
      genetic diversity of Chinese helminths and candidate vaccine antigens. Evidence
      from biogeography, genetics, and systematics suggests that the genetic
      diversification of Chinese helminths and their vectors is an ongoing evolutionary
      process that began 12 million years ago near the convergence of major Asian river
      systems. Construction of the Three Gorges Super Dam on the Yangtze River may
      promote the emergence and reemergence of new helminths and their snail vectors

PMID- 9284376
TI  - Flea-borne rickettsioses: ecologic considerations.
AB  - Ecologic and economic factors, as well as changes in human behavior, have
      resulted in the emergence of new and the reemergence of existing but forgotten
      infectious diseases during the past 20 years. Flea-borne disease organisms (e.g.,
      Yersinia pestis, Rickettsia typhi, R. felis, and Bartonella henselae) are widely
      distributed throughout the world in endemic-disease foci, where components of the
      enzootic cycle are present. However, flea-borne diseases could reemerge in
      epidemic form because of changes in vector-host ecology due to environmental and
      human behavior modification. The changing ecology of murine typhus in southern
      California and Texas over the past 30 years is a good example of urban and
      suburban expansion affecting infectious disease outbreaks. In these areas, the
      classic rat-flea-rat cycle of R. typhi has been replaced by a peridomestic animal
      cycle involving, e.g., free-ranging cats, dogs, and opossums and their fleas. In
      addition to the vector-host components of the murine typhus cycle, we have
      uncovered a second typhuslike rickettsia, R. felis. This agent was identified
      from the blood of a hospitalized febrile patient and from opossums and their
      fleas. We reviewed the ecology of R. typhi and R. felis and present recent data
      relevant to the vector biology, immunology, and molecular characterization and
      phylogeny of flea-borne rickettsioses.

PMID- 9284377
TI  - Aedes albopictus in the United States: ten-year presence and public health
      implications.
AB  - Since its discovery in Houston, Texas, in 1987, the Asian "tiger mosquito" Aedes
      albopictus has spread to 678 counties in 25 states. This species, which readily
      colonizes container habitats in the peridomestic environment, was probably
      introduced into the continental United States in shipments of scrap tires from
      northern Asia. The early pattern of dispersal followed the interstate highway
      system, which suggests further dispersal by human activities. The Public Health
      Service Act of 1988 requires shipments of used tires from countries with Ae.
      albopictus to be treated to prevent further importations. Given the extensive
      spread of the mosquito in the United States, it is questionable whether such a
      requirement is still justified. Ae. albopictus, a major biting pest throughout
      much of its range, is a competent laboratory vector of at least 22 arboviruses,
      including many viruses of public health importance. Cache Valley and eastern
      equine encephalomyelitis viruses are the only human pathogens isolated from U.S.
      populations of Ae. albopictus. There is no evidence that this mosquito is the
      vector of human disease in the United States.

PMID- 9284375
TI  - Vancomycin-resistant enterococci outside the health-care setting: prevalence,
      sources, and public health implications.
AB  - Although nosocomial acquisition and subsequent colonization of vancomycin
      resistant enterococci (VRE), an emerging international threat to public health,
      has been emphasized in the United States, colonization among nonhospitalized
      persons has been infrequently documented. In contrast, in Europe, colonization
      appears to occur frequently in persons outside the health-care setting. An
      important factor associated with VRE in the community in Europe has been
      avoparcin, a glycopeptide antimicrobial drug used for years in many European
      nations at subtherapeutic doses as a growth promoter in food-producing animals.
      In Europe, evidence suggests that foodborne VRE may cause human colonization.
      Although avoparcin has never been approved for use in the United States,
      undetected community VRE transmission may be occurring at low levels. Further
      studies of community transmission of VRE in the United States are urgently
      needed. If transmission with VRE from unrecognized community sources can be
      identified and controlled, increased incidence of colonization and infection
      among hospitalized patients may be prevented.

PMID- 9284378
TI  - Using a mathematical model to evaluate the efficacy of TB control measures.
AB  - We evaluated the efficacy of recommended tuberculosis (TB) infection control
      measures by using a deterministic mathematical model for airborne contagion. We
      examined the percentage of purified protein derivative conversions under various
      exposure conditions, environmental controlstrategies, and respiratory protective
      devices. We conclude that environmental control cannot eliminate the risk for TB
      transmission during high-risk procedures; respiratory protective devices, and
      particularly high-efficiency particulate air masks, may provide nearly complete
      protection if used with air filtration or ultraviolet irradiation. Nevertheless,
      the efficiency of these control measures decreases as the infectivity of the
      source case increases. Therefore, administrative control measures (e.g.,
      indentifying and isolating patients with infectious TB) are the most effective
      because they substantially reduce the rate of infection.

PMID- 9284380
TI  - Deer ticks (Ixodes scapularis) and the agents of Lyme disease and human
      granulocytic ehrlichiosis in a New York City park.
AB  - Rodent trapping and drag sampling in Van Cortlandt Park, New York City, yielded
      all stages of Ixodes scapularis, the deer tick vector of Lyme disease and human
      granulocytic ehrlichiosis (HGE). Polymerase chain reaction analyses of the ticks
      showed Borrelia burgdorferi and the Ehrlichia sp. that causes HGE.

PMID- 9284379
TI  - Borna disease virus infection in animals and humans.
AB  - The geographic distribution and host range of Borna disease (BD), a fatal
      neurologic disease of horses and sheep, are larger than previously thought. The
      etiologic agent, Borna disease virus (BDV), has been identified as an enveloped
      nonsegmented negative-strand RNA virus with unique properties of replication.
      Data indicate a high degree of genetic stability of BDV in its natural host, the
      horse. Studies in the Lewis rat have shown that BDV replication does not directly
      influence vital functions; rather, the disease is caused by a virus-induced T
      cell mediated immune reaction. Because antibodies reactive with BDV have been
      found in the sera of patients with neuropsychiatric disorders, this review
      examines the possible link between BDV and such disorders. Seroepidemiologic and
      cerebrospinal fluid investigations of psychiatric patients suggest a causal role
      of BDV infection in human psychiatric disorders. In diagnostically unselected
      psychiatric patients, the distribution of psychiatric disorders was found to be
      similar in BDV seropositive and seronegative patients. In addition, BDV
      seropositive neurologic patients became ill with lymphocytic meningoencephalitis.
      In contrast to others, we found no evidence is reported for BDV RNA, BDV
      antigens, or infectious B DV in peripheral blood cells of psychiatric patients.

PMID- 9284381
TI  - Jail fever (epidemic typhus) outbreak in Burundi.
AB  - We recently investigated a suspected outbreak of epidemic typhus in a jail in
      Burundi. We tested sera of nine patients by microimmunofluorescence for
      antibodies to Rickettsia prowazekii and Rickettsia typhi. We also amplified and
      sequenced from lice gene portions specific for two R. prowazekii proteins: the
      gene encoding for citrate synthase and the gene encoding for the rickettsial
      outer membrane protein. All patients exhibited antibodies specific for R.
      prowazekii. Specific gene sequences were amplified in two lice from one patient.
      The patients had typical clinical manifestations, and two died. Molecular
      techniques provided a convenient and reliable means of examining lice and
      confirming this outbreak. The jail-associated outbreak predates an extensive
      ongoing outbreak of louse-borne typhus in central eastern Africa after civil war
      and in refugee camps in Rwanda, Burundi (1), and Zaire.

PMID- 9284382
TI  - Hantavirus transmission in the United States.
AB  - In 1996, investigation of a hantavirus pulmonary syndrome (HPS) outbreak in
      southern Argentina found evidence of person-to-person transmission of a
      hantavirus. The infection control ramifications of this finding led to this
      review of hantavirus epidemiology in the United States; the review suggests that
      Sin Nombre virus infection is rarely, if ever, transmitted from person to person
      and that existing guidelines for prevention of HPS remain appropriate for North
      America.

PMID- 9284383
TI  - Population dynamics of the deer mouse (Peromyscus maniculatus) and Sin Nombre
      virus, California Channel Islands.
AB  - Hantavirus pulmonary syndrome, first documented in 1993, is caused by Sin Nombre
      virus (SNV), which is carried by the Peromyscus species. In 1994, high SNV
      antibody prevalence was identified in deer mice from two California Channel
      Islands. We sampled two locations on three islands to estimate mouse population
      density and SNV prevalence. Population flux and SNV prevalence appear to vary
      independently.

PMID- 9284384
TI  - Emerging quinolone-resistant Salmonella in the United States.
AB  - We conducted a national survey of antimicrobial resistance in human clinical
      isolates of Salmonella between July 1, 1994, and June 30, 1995. Every tenth
      nontyphoidal Salmonella isolate received at state public health laboratories in
      the United States during this period was tested for resistance to 12
      antimicrobial agents, including two quinolones, nalidixic acid, and
      ciprofloxacin. Emerging quinolone resistance was detected; of 4,008 isolates
      tested, 21 (0.5%) were resistant to nalidixic acid, and one (0.02%) was resistant
      to ciprofloxacin. Continued surveillance for quinolone-resistant Salmonella is
      necessary, particularly after the recent approval of a fluoroquinolone for use in
      animals intended for food in the United States.

PMID- 9284386
TI  - Molecular epidemiologic investigations of Mycoplasma gallisepticum conjunctivitis
      in songbirds by random amplified polymorphic DNA analyses.
AB  - An ongoing outbreak of conjunctivitis in free-ranging house finches (Carpodacus
      mexicanus) began in 1994 in the eastern United States. Bacterial organisms
      identified as Mycoplasma gallisepticum (MG) were isolated from lesions of
      infected birds. MG was also isolated from a blue jay (Cyanocitta cristata) that
      contracted conjunctivitis after being housed in a cage previously occupied by
      house finches with conjunctivitis, and from free-ranging American goldfinches
      (Carduelis tristis) in North Carolina in 1996. To investigate the molecular
      epidemiology of this outbreak, we produced DNA fingerprints of MG isolates by
      random amplification of polymorphic DNA (RAPD). We compared MG isolates from
      songbirds examined from 1994 through 1996 in 11 states, representing three host
      species, with vaccine and reference strains and with contemporary MG isolates
      from commercial poultry. All MG isolates from songbirds had RAPD banding patterns
      identical to each other but different from other strains and isolates tested.
      These results indicate that the outbreak of MG in songbirds is caused by the same
      strain, which suggests a single source; the outbreak is not caused by the vaccine
      or reference strains analyzed; and MG infection has not been shared between
      songbirds and commercial poultry.

PMID- 9284385
TI  - Multidrug-resistant enteroaggregative Escherichia coli associated with persistent
      diarrhea in Kenyan children.
AB  - To study the association of multidrug-resistant enteroaggregative Escherichia
      coli with persistent diarrhea in Kenyan children, stool specimens were obtained
      from 862 outpatients under 5 years of age from July 1991 to June 1993. E. coli
      O44 was identified as the sole bacterial pathogen in four patients experiencing
      at least 14 days of fever, vomiting, and diarrhea. Disk diffusion testing showed
      E. coli O44 resistance to tetracycline, ampicillin, erythromycin, trimethoprim
      sulphamethoxazole, and amoxicillin/clavulanate and sensitivity to
      chloramphenicol, nalidixic acid, azithromycin, and cefuroxime. Further studies
      are needed to clarify the epidemiology, clinical spectrum, and pathogenesis of
      enteroaggregative E. coli infection.

PMID- 9284387
TI  - Reevaluating the molecular taxonomy: is human-associated Cyclospora a mammalian
      Eimeria species?
AB  - Human-associated Cyclospora is a coccidian parasite that causes diarrheal
      disease. A reevaluation of the parasite's molecular taxonomy that takes into
      account newly published data for seven Eimeria species shows that Cyclospora
      belongs to the Eimeria clade (Eimeriidae family). The Cyclospora branch on the
      phylogenetic tree is between the branches of the eight avian and two mammalian
      Eimeria species that have been evaluated to date. Furthermore, preliminary
      results indicate that Cyclospora and Isospora belli, another coccidian parasite
      that causes diarrheal disease in humans, belong to different families. To improve
      our understanding of the taxonomy of human-associated Cyclospora, molecular
      evaluation of isolates of additional Cyclospora and Eimeria species is needed.

PMID- 9284388
TI  - Rapid increase in the prevalence of metronidazole-resistant Helicobacter pylori
      in the Netherlands.
AB  - The prevalence of primary metronidazole resistance of Helicobacter pylori was
      studied in one Dutch hospital from 1993 to 1996 and in two additional Dutch
      hospitals in 1993 and 1996. All cultures of antral biopsy specimens yielding H.
      pylori in the study period were evaluated, except those from patients who had
      received anti-H. pylori treatment; 1,037 H. pylori strains, all from different
      patients were included. Metronidazole resistance was determined by disk diffusion
      in 1993 and by Epilipsometer-test in 1994 to 1996. Metronidazole resistance
      increased from 7% (18/245) in 1993 to 32% (161/509) in 1996. More patients with
      nonulcer dyspepsia and more non-Western European patients were seen in 1996 than
      in 1993, but age and sex differences were not observed. A comparable increase in
      metronidazole resistance was observed in both nonulcer dyspepsia patients and
      peptic ulcer patients, and the prevalence of metronidazole resistance in Western
      Europeans increased from 5% in 1993 to 28% in 1996.

PMID- 9284391
TI  - Host genes and HIV infection: implications and applications.

PMID- 9284390
TI  - Using laboratory-based surveillance data for prevention: an algorithm for
      detecting Salmonella outbreaks.
AB  - By applying cumulative sums (CUSUM), a quality control method commonly used in
      manufacturing, we constructed a process for detecting unusual clusters among
      reported laboratory isolates of disease-causing organisms. We developed a
      computer algorithm based on minimal adjustments to the CUSUM method, which
      cumulates sums of the differences between frequencies of isolates and their
      expected means; we used the algorithm to identify outbreaks of Salmonella
      Enteritidis isolates reported in 1993. By comparing these detected outbreaks with
      known reported outbreaks, we estimated the sensitivity, specificity, and false
      positive rate of the method. Sensitivity by state in which the outbreak was
      reported was 0%(0/1) to 100%. Specificity was 64% to 100%, and the false-positive
      rate was 0 to 1.

PMID- 9284389
TI  - An increase in hookworm infection temporally associated with ecologic change.
AB  - This report describes a significant increase in the prevalence of hookworm
      infection in an area of Haiti where intestinal parasites are common, but hookworm
      has not been common. Changing environmental conditions, specifically
      deforestation and subsequent silting of a local river, have caused periodic
      flooding with deposition of a layer of sandy loam topsoil and increased soil
      moisture. We speculate that these conditions, conducive to transmission of the
      infection, have allowed hookworm to reemerge as an important human pathogen.

PMID- 9284394
TI  - Acute epiglottitis due to Pasteurella multocida in an adult without animal
      exposure.

PMID- 9284393
TI  - Paratyphoid fever due to Salmonella enterica serotype Paratyphi A.

PMID- 9284392
TI  - Controversies in the management of cysticercosis.

PMID- 9284398
TI  - [Pathogenesis of hypertension].

PMID- 9284395
TI  - Hemolytic uremic syndrome surveillance to monitor trends in infection with
      Escherichia coli O157:H7 and other shiga toxin-producing E. coli.

PMID- 9284399
TI  - [Renin-angiotensin system].

PMID- 9284401
TI  - [Prostaglandin and kallikrein-kinin systems].
AB  - We reviewed the recent advances in the molecular characterization of prostanoid
      and bradykinin receptors. Prostanoids and bradykinin exert versatile actions in
      diverse tissues and cells through specific cell surface receptors. Molecular
      biological studies revealed the primary structure of eight types and subtypes of
      prostanoid receptors from various species. These include the thromboxane A2
      receptor, prostacyclin receptor, prostaglandin (PG) F receptor, PGD receptor and
      four subtypes of PGE receptor (EP1, EP2, EP3 and EP4). There are four subtypes of
      bradykinin receptor (BK1, BK2, BK3 and BK4), but it is still unknown about the
      detail of BK3 and BK4. These results also have achieved the remarkable
      development in the field of human hypertension.

PMID- 9284400
TI  - [Pathophysiological roles of human chymase].
AB  - Angiotensin (Ang) II plays an important role in cardiovascular homeostasis such
      as regulation of blood pressure and tissue remodeling. Alternative Ang II-forming
      pathways, independent of Ang I converting enzyme (ACE), have been reported.
      Several serine proteinases including kallikrein, cathepsin G and chymase appear
      to be involved in ACE-independent Ang II formation in vivo. Among them,
      biochemical analysis revealed that chymase is a highly efficient Ang II-forming
      enzyme with a high substrate specificity against Ang I and is rich in various
      human tissues. However, the pathophysiological roles of chymase have not yet been
      clarified. Recent reports from us and others indicated that chymase seems to be
      related to development of atherosclerosis, cardiomyopathy, remodeling of
      cardiovascular tissues, rheumatoid arthritis and etc. In this review article, the
      recent findings for chymase related to cardiovascular diseases are summarized.

PMID- 9284402
TI  - [Catecholamine and dopamine].
AB  - Almost all the genes of the enzymes which synthesize and metabolize the
      catecholamines (dopamine, norepinephrine, epinephrine) have been cloned and the
      gene targeting technology have been applied to introduce the gene knockout mouse
      such as thyrosine hydroxylase and dopamine beta hydroxylase. At least nine
      adrenergic receptors and five dopamine receptors have been cloned, which include
      alpha 1A-, alpha 1 B-, alpha 1 D-, alpha 2 A-, alpha 2B-, alpha 2C-, beta 1-,
      beta 2-, beta 3-adrenergic receptors and D1-, D2-, D3-, D4-, D5-dopamine
      receptors. Transgenic mouse as well as gene knockout mouse of these genes have
      been also produced. Furthermore, intracellular signal transduction systems of the
      catecholamines have been clarified using molecular techniques, including nine
      subtypes of adenylyl cyclase. Using these cloned genes and transgenic and gene
      knockout mouse, more detailed features of the catecholamine systems and those
      receptors and intracellular signal transduction systems will be clarified in near
      future.

PMID- 9284403
TI  - [Natriuretic peptide system].
AB  - Natriuretic peptide system consists of three endogenous ligands, ANP (atrial
      natriuretic peptide), BNP (brain natriuretic peptide) and CNP (C-type natriuretic
      peptide), and three receptor subtypes, natriuretic peptide receptor (NPR)-A or
      guanylate cyclase (GC)-A and NPR-B or GC-B and C receptor (NPR-C). ANP and BNP
      are mainly secreted from the atrium and ventricle of the heart respectively to
      act as cardiac hormones whereas CNP is secreted from the endothelium to act as an
      endothelium-derived relaxing peptide. ANP and BNP regulate body fluid and blood
      pressure to reduce cardiac pre- and after-load. Recent molecular biology and
      developmental biotechnology demonstrated the physiological role of ANP and BNP
      for the determination of basal blood pressure. CNP can modulate the phenotype of
      vascular smooth muscle cells to regulate vascular remodeling. Therefore,
      natriuretic peptide system is implicated in the pathophysiology of hypertension,
      congestive heart failure atherosclerosis and renal diseases. Clinical application
      of natriuretic peptide system is actively going on progress. Determination of
      plasma ANP and BNP levels are useful for the evaluation of congestive heart
      failure, cardiac hypertrophy and acute myocardial infarction. Infusion of ANP
      improves acute heart failure. Application of NEP (neutral endopeptidase)
      inhibitor for the treatment of congestive heart failure and hypertension is under
      clinical trial.

PMID- 9284404
TI  - [Blood pressure-regulating factor vasopressin].
AB  - The DNA of AVP vasopressin (AVP) is composed of 3 exons (A, B, C) and 2 introns
      (I, II). Following transcription, translation, and processing AVP(MW 1081) is
      produced. AVP receptors (VR) are classified into V1aR, V1bR and V2R. V1aR is
      composed of 418 amino acids (AA) and its MW is 46745. V1aR is in the vascular
      smooth muscle (VSM) and activates the phosphatidylinositol system, leading to the
      contraction of VSM. V1bR is composed of 424 AA and its MW 47034. It's second
      messenger systems are obscure, but V1bR is responsible for ACTH release. V2R is
      composed of 371 AA and its MW 40285. V2R is in the kidney and enhances the
      production of cAMP, leading to renal water and urea reabsorption.

PMID- 9284405
TI  - [Insulin, as a regulating factor of blood pressure].
AB  - In patients with hypertension, insulin resistance and hyperinsulinemia are more
      prevalent than in normal individuals. Furthermore, the prevalence of hypertension
      in diabetic patients is higher than in nondiabetic individuals. Insulin
      resistance has been implicated in the common mechanisms underlying diabetes,
      hypertension, hyperlipidemia and obesity. A number of mechanisms have been
      proposed to account for the elevation of BP secondary to hyperinsulinemia, such
      as 1) increased tubular reabsorption of sodium ions, 2) increased intracellular
      sodium and calcium ions, 3) increased sympathetic nervous activity, and 4)
      proliferation of vascular smooth muscle cells. Moreover, hypertension was
      reported to be a possible cause of insulin resistance. The detailed mechanism of
      insulin leading hypertension are still under investigation.

PMID- 9284406
TI  - [PTH, PTHrP, and CGRP in hypertension research].
AB  - Parathyroid hormone (PTH), a key hormone regulating plasma Ca level, is elevated
      in some essential hypertension, and conversly, hyperparathyroidism is associated
      with elevated blood pressure. However, such an effect would be paradoxical
      because PTH is a potent vasodilator. Parathyroid hormone-related peptide (PTHrP),
      which could act in a autocrine and paracrine manner in vascular smooth muscle
      cells and endothelial cells, would be a more potent vasodilator and could be
      produced in hypertensive vascular tissue. Calcitonin gene related peptide (CGRP),
      37-amino acid neuropeptide results from alternative processing from calcitonin
      gene, is vasodilating peptide, and is localized in the central and peripheral
      nervous system involved in cardiovascular regulation. In some essential
      hypertensive patients, CGRP is reported to be at a low level.

PMID- 9284407
TI  - [Endothelin and nitric oxide].
AB  - Endothelin-1 (ET-1) is an endothelium-derived vasoconstrictor peptide, whereas
      nitric oxide (NO) is a potent endothelium-derived vasorelaxing factor synthesized
      from L-arginine by NO synthase (NOS). ET-1 and NO exert many biological actions
      in a counter-regulatory manner in vascular remodeling and vascular tonus.
      Furthermore, there exists a close interaction between ET-1 and NO:ET-1 stimulates
      NO generation, while NO down-regulates the expression of ET-1 gene.

PMID- 9284409
TI  - [Endogenous digitalis-like factor].
AB  - Evidence suggests the existence of a Na,K-ATPase inhibitor, so called endogenous
      digitalis-like factor (EDLF), in plasma. This substance has been postulated to
      enhance renal tubular sodium excretion and to increase peripheral vascular
      resistance. Recently, plant ouabain or its isomer (ouabain-like compound, OLC)
      was purified from human plasma and bovine hypothalamic extract. The OLC is
      considered to be a candidate for the EDLF. The OLC has been implicated in the
      pathogenesis of sodium-dependent hypertension. Furthermore, accumulating evidence
      suggests central nervous system as a site of hypertensinogenic action of OLC.

PMID- 9284408
TI  - [Adrenomedullin and PAMP].
AB  - "Adrenomedullin (AM)" is a novel hypotensive peptide which was discovered in
      human pheochromocytoma by monitoring the elevating activity of platelet cAMP. In
      addition, a novel 20 residues hypotensive peptide, termed "proadrenomedullin N
      terminal 20 peptide" (PAMP) is processed from proadrenomedullin. By RNA blot
      analysis, AM mRNA was found to be highly expressed in several tissues including
      ventricle, lung, kidney, aorta and vascular cultured cells as well as in adrenal
      medulla. Both AM and PAMP shows hypotensive effects in anesthetized rats, but
      exhibits different hypotensive mechanism. AM possesses multiple biological
      effects involving in cardiovascular homeostasis. Further, plasma AM as well as
      PAMP concentrations significantly increased in various cardiovascular diseases
      including hypertension and congestive heart failure. The present review
      summarizes the recent advancement of AM research and demonstrated that AM and
      PAMP are important vasoactive peptides involved in the physiology and
      pathophysiology of circulation control.

PMID- 9284410
TI  - [Hypertension and steroid hormones].
AB  - Mineralocorticoid excess causes hypertension by facilitating the sodium retension
      at renal tubules. Such mechanism operates in hypertension such as primary
      hyperaldosteronism and some forms of congenital adrenal hyperplasia. Recently,
      deficient cortisol metabolism in the aldosterone target organ has been recognized
      as a novel form of hypertension known as apparent mineralocorticoid excess. In
      this review hypertensive disorders caused by adrenal cortical hormones is briefly
      stated.

PMID- 9284411
TI  - [Central autonomic control in human hypertension].
AB  - Sympathetic nerve fibers innervating the heart and blood vessels exhibit tonic
      activity which originates from vasomotor neurons in the rostral ventrolateral
      medulla (RVLM). Whether sympathetic nerve activity (SNA) is elevated in humans
      with essential hypertension is still unsettled. Recording of muscle SNA (MSNA) by
      the microneurographic method mostly points to elevated SNA in hypertensives
      including borderline and mildly hypertensive patients. Exaggerated MSNA is most
      conspicuous in the accelerated hypertensives. Power spectral analyses of heart
      rate and blood pressure variability provide controversial results on this issue.
      Nevertheless, most studies demonstrate altered sympathetic cardiovascular control
      in hypertensive subjects. In young borderline hypertensives, the sympathetic
      response to mental stress or passive tilting is exaggerated, whereas in elderly
      subjects it is attenuated.

PMID- 9284412
TI  - [Molecular mechanism of cardiac hypertrophy and dysfunction].
AB  - We examined the signal transduction pathway for the development of cardiac
      hypertrophy induced by high blood pressure. The activities of Raf-1 kinase (Raf
      1), mitogen-activated protein kinase kinase (MAPKK), MAP kinases (MAPKs) and 90
      kDa ribosomal S6 kinase (p90rsk) was examined by passively stretching neonatal
      rat cardiomyocytes in vitro. Mechanical stretch activated these protein kinases
      transiently and sequentially: the maximal activation of Raf-1, MAPKK, MAPKs and
      p90rsk was observed at 2 minutes, 5 minutes, 8 minutes and 10 approximately 30
      minutes, respectively. Both angiotensin II (AngII) and endothelin-1 (ET-1) were
      constitutively secreted from cultured cardiomyocytes, and a significant increase
      in the concentration was recognized in the culture medium of cardiomyocytes
      within 10 minutes after stretch. ET-1 mRNA levels were also increased in
      cardiomyocytes at 30 minutes after stretch. Moreover, ET-1 and AngII
      synergistically activated Raf-1 and MAPKs in cultured cardiomyocytes. In
      conclusion, mechanical stretch stimulates secretion and production of AngII and
      ET-1 in cultured cardiomyocytes, and both vasoconstrictive peptides may play an
      important role in mechanical stress (high blood pressure)-induced cardiac
      hypertrophy.

PMID- 9284414
TI  - [Renal function and hemodynamics in hypertension].
AB  - Hypertension is one of important causes of impairment in renal function.
      Glomerular filtration rate (GFR) remains stable while renal blood flow (RBF)
      declines in patients with long-term essential hypertension, resulting in an
      increased filtration fraction. Myogenic response of afferent arterioles and
      tubuloglomerular feedback to maintain RBF and GFR and sodium homeostasis can be
      impaired in salt-sensitive hypertension, whereas they are relatively normal in
      essential hypertension and its rat model. Position of pressure-natriuresis curve
      is shifted to the right without alteration in the slope of the curve in essential
      (non-salt-sensitive) hypertension, whereas the slope is significantly decreased
      in salt-sensitive hypertension, such as nephritis-related hypertension and
      diabetic nephropathy because of decreased ultrafiltration coefficient and
      increased sodium reabsorption.

PMID- 9284415
TI  - [Genetically engineered mice for study of human hypertension].
AB  - Human essential hypertension is generally recognized as a multifactorial disease
      based on genetic diathesis. Despite the usefulness of SHR and Dahl rats as
      laboratory tools, the genetic diathesis including the development of hypertension
      in these rats remains unclear. Rapid advances in embryonic engineering and
      molecular biological techniques may make it possible to develop transgenic mice
      and gene-targeted mice and open new avenues for the molecular investigation of
      human disease. This report introduces genetically engineered mice with
      hypertension and hypotension.

PMID- 9284416
TI  - [Diagnostic criteria and staging for patients with hypertension].

PMID- 9284413
TI  - [Vasculature in hypertension].
AB  - Hypertensive disease causes vascular complications, which are clinically
      important. Reversely, vascular dysfunction accelerates hypertension and its
      complication. The structural changes in vasculature alter vascular function but
      blood vessels, which does not have structural changes, also exhibit abnormal
      vascular function. Recently, it has been recognized that hemodynamic factors
      modifis vascular function. Especially, shear stress affects vascular endothelial
      function to regulate vascular tone, gene expression, and leukocyte adhesion,
      which intimately related to pathogenesis of hypertensive disease.

PMID- 9284417
TI  - [Methods of 24-hour blood-pressure measurement].
AB  - With the recently growing use of portable devices for ambulatory blood pressure
      (BP) monitoring (ABPM), 24-hour BP measurement is often being performed even
      clinically. But such measurements as daytime BPs vary according to body position
      (sitting or standing) and motion (physical activity), ambient temperature, and
      the activities of the autonomic nervous system. Since it is capable of measuring
      all these factors (temperature, body position, acceleration, indirect BP, ECG and
      power spectral of heart rate variability) simultaneously, the multi-biomedical
      recorder (TM2425) we have developed is useful in objective evaluations of 24-hour
      BP values and its cause of BP variation. In addition, it is helpful in assessing
      minimal sleep-time BP (base BP) the most significant nighttime BP value.

PMID- 9284418
TI  - [Ultrasound examination for hypertension].
AB  - The echocardiographic determination of left ventricular mass is useful to
      evaluate the severity and the prognosis of hypertension. In addition to this
      determination, the echocardiographic assessment of left ventricular morphology is
      also proposed as one of important parameters to implicate the prognosis.
      Recently, the clinical significance of intimal-media thickness, plaque, and
      diameter of carotid artery obtained by an ultrasound examination for hypertension
      has been discussed. While these parameters correlate well with blood pressure
      level and left ventricular mass, further studies are needed to establish the
      usefulness of the ultrasound examination of carotid artery. As a tool for
      research purposes, ultrasound examination is also applicable to examine organ
      blood flow, arterial distensibility, and arterial endothelial function. Thus,
      ultrasound examination for hypertension is promising either in clinical practices
      and research purposes.

PMID- 9284420
TI  - [Non pharmacological therapy in hypertensive patients--effect of physical
      exercise on hypertension].
AB  - Many well-controlled studies have shown that non-pharmacological treatments are
      effective in lowering blood pressure, especially in mild hypertensive. The
      principle proven measures are (1) reductions of sodium intake, body weight (in
      obesity) and alcohol and (2) physical exercise. Physical exercise has been proven
      for the antihypertensive effectiveness last ten years. We have carried out mine
      studies and demonstrated the reduction of blood pressure by mild (approximately
      50% of maximum oxygen uptake) intensity cycle ergo meter (60 min. x 3 times a
      week x 10 week) by -11/-6 mmhg. We found sympathicolytic action and plasma volume
      depletion for the depressor effects. In hypertensive patients, life style
      modifications including exercise are the first step in the treatments of mild
      hypertensives.

PMID- 9284419
TI  - [Current epidemiology of hypertension in Japan].
AB  - In 1960, stroke mortality in Japan was the highest among industrialized
      countries, while CHD mortality was the lowest. Stroke mortality for men and women
      aged 30-69 years, however, declined by 80% during the 1965-90 years and CHD
      mortality also declined during the same period. Among risk factors, trends in
      blood pressure level and the prevalence of hypertension were very compatible with
      those in stroke mortality. Serum total cholesterol level has increased
      remarkably, however, CHD mortality has not increased. This may be explained by
      the decline in population blood pressure level and the prevalence of
      hypertension, and decreased smoking rate.

PMID- 9284421
TI  - [Diuretics for therapy of patients with hypertension].
AB  - Diuretic agents have antihypertensive effects mainly be decreasing extracellular
      volume and cardiac output. These diuretics are described with regard to mechanism
      of action, site of action, adverse effects, and drug interactions. Thiazide
      diuretics inhibit the Na(+)-Cl- symporter in the distal convoluted tubule, by
      competing for the Cl- binding site, and increase Na+ and Cl- excretion. Loop
      diuretics are inhibitors of Na(+)-K(+)-2Cl- symporter in the thick ascending limb
      of the loop of Henle. However, loop diuretics are not the diuretic of first
      choice and should be reserved for patients in whom other diuretics or
      antihypertensive drugs do not result in a satisfactory response. The potassium
      sparing diuretics are used primarily to reduce the kaliuresis and potenciate the
      hypotensive effect of a thiazide.

PMID- 9284423
TI  - [Alpha-adrenoceptor antagonist (blocker)].
AB  - Alpha adrenergic receptors localized in blood vessels, heart, and kidneys as well
      as pre- and post-synaptic membrane are significantly important for controlling
      blood pressure. The treatment of alpha-adrenoceptor blocking drugs induce
      vasodilatation subsequently lowering blood pressure. Selective alpha-1
      adrenoceptor blocking drugs (alpha-1 blockers) are recommended as a first line
      treatment of hypertension, because of their desirable effect on lipid and glucose
      metabolism. alpha-1 blockers decrease in total cholesterol and triglycerides, and
      increase in HDL-cholesterol. It is suggested that alpha-1 blockers improve
      insulin tolerance, cardiomegaly and atherosclerosis. Although they have many
      beneficial effect, we should consider adverse effects (orthostatic hypotension,
      flushing, etc.).

PMID- 9284422
TI  - [beta-blocker in hypertension].
AB  - The beta-blockers are either nonselective and affect both beta 1- and beta 2
      receptors, are relatively selective for the alpha 1 subclass, or are able to have
      activity against alpha-receptors. The ability to reduce blood pressure is very
      common among all beta-blockers, and beta-blockers are recommended for one of the
      first-line drugs in hypertension treatment by JNCV. beta-blockers should be used
      considering their pharmacological properties and potential side effects,
      according to the pathophysiological conditions involved. The superiority of beta
      blocker to other types of antihypertensive drug has not yet been evidenced by
      larger scale clinical trials which have been carried out so far. To verify more
      precisely the usefulness of beta-blocker in hypertension treatment, more large
      scale clinical trials are required to be carried out. The fixed-dose combination
      of beta-blockers and calcium blockers appears to be more effective rather than
      that of beta-blockers and diuretics.

PMID- 9284425
TI  - [Angiotensin-converting enzyme inhibitors: recent therapeutic aspect].
AB  - Angiotensin-converting enzyme (ACE) inhibitors now have an accepted place in the
      treatment of hypertension and congestive heart failure. With the discovery and
      development of captopril, several other ACE inhibitors have been synthesized and
      introduced for clinical use. All ACE inhibitors bind to zinc ions located in the
      active site of the ACE molecule. ACE inhibitors can be classified according to
      the ligand of the zinc ion of ACE, into 3 different structural types: (1) the
      first type such as captopril has a sulphhydryl moiety as the ligand; (2) the
      second type such as enalapril uses a carboxyl moiety as the ligand; (3) the third
      type such as fosinopril uses neither a sulphhydryl nor carboxyl group, but a
      phosphinic acid as the zinc binding moiety. ACE inhibitors can also be classified
      according to the excretion route of their active moiety, into 2 different
      excretion route types:(1) excreated mainly through the kidney such as captopril,
      enalaprilat, lisinopril, benazeprilat, imdaprilat, trandraprilat, etc.; (2)
      excreated both in the bile and urine such as fosinoprilat, temocaprilat,
      zofenoprilat etc. ACE inhibitors have clinically beneficial effects not only for
      patients with either hypertension or congestive heart failure, but also can be
      used to prevent the progression of renal dysfunction induced by hypertension and
      diabetes mellitus.

PMID- 9284424
TI  - [Calcium channel blocker for therapy of patients with hypertension].
AB  - Calcium channel blocker (CCB) is one of the most frequently prescribed
      cardiovascular drugs. Two main classes of CCBs, dihydropyridines and
      benzothiazepines, are now clinically available for the treatment of hypertension
      in Japan. Both drugs inhibit the inward current of calcium ions through the L
      type calcium channels. However CCBs have markedly different chemical structures
      and different effects on cardiovascular system. Therefore, in the present paper,
      their pharmacokinetic properties and interactions with other drugs are reviewed,
      and newly developed CCB are also described.

PMID- 9284426
TI  - [Angiotensin receptor antagonist for therapy of patients with hypertension].
AB  - Nonpeptide angiotensin II type 1-receptor antagonists, AT1 receptor antagonists
      are newly developed and useful drugs for hypertension and congestive heart
      failure. In Japan, the efficacy and safety of losartan and candesartan cilexetil
      in patients with essential hypertension have been evaluated by the double-blind,
      parallel group-comparison study using enalapril as control drug. Both trials
      revealed that these drugs showed a hypotensive effect comparable to that of
      enalapril with a high safety since the adverse drug reaction of cough was
      recognized in very few patients. Furthermore, a recent randomised trial of
      losartan versus captopril in patients over 65 with heart failure, evaluation of
      losartan in the elderly study (ELITE), showed that losartan was associated with a
      lower mortality than that found with captopril. Further studies will clarify
      differences in protection of cardiovascular system with a long-term treatment
      between AT1, receptor antagonists and angiotensin-converting enzyme inhibitors.

PMID- 9284427
TI  - [Centrally acting sympathetic inhibitors for therapy of patients with
      hypertension].
AB  - The blood pressure is maintained by the tonic vasomotor activity of efferent
      sympathetic neurons which are tonically regulated by the rostral ventrolateral
      medulla (RVLM) in the brain. The alpha 2-adrenoceptor agonist such as clonidine,
      guanabenz and guanfacine, acts on RVLM to decrease sympathetic neuron activity
      and lower blood pressure. Drug such as alpha-methyldopa, through its metabolite
      alpha-methylnoradrenaline, acts like clonidine as an alpha 2-adrenoceptor agonist
      in the brain. Clonidine and allied drugs except for alpha-methyldopa also bind to
      imidazoline receptors, which is believed to mediate the hypotensive action. The
      centrally acting antihypertensive drugs are used for treatment of moderate to
      severe forms of hypertension and are effective in patients with renal failure.
      The treatment with these drugs induces central nervous system side effect of
      sedation and drowsiness, which limits the clinical usefulness and are believed to
      be mediated by central alpha 2-adrenoceptors. The new imidazoline compounds,
      rilmenidine and moxonidine, which selectively act on imidazoline receptors, may
      be a useful antihypertensive drug without such central side effects.

PMID- 9284428
TI  - [Large, long-term, randomized trials and meta-analysis of therapy of patients
      with hypertension].
AB  - Over the past few decades, numerous randomized controlled studies of the
      treatment of hypertension have been conducted in Western countries to determine
      whether blood pressure reduction reduces the risk of stroke and myocardial
      infarction. Diuretics and beta blockers, because they have been shown in clinical
      trials to reduce cardiovascular morbidity and mortality, are the preferred drugs
      of first choice. No direct evidence yet supports the theoretical advantages of
      calcium channel blockers and ACE inhibitors over diuretics and beta blockers.
      Because East Asian nations differ culturally from Western countries, it is very
      difficult to conduct a randomized trials, thus, there were no reports of large,
      long-term, randomized placebo-controlled clinical trials of hypertension.

PMID- 9284429
TI  - [Treatment of hypertension associated with diabetes mellitus].
AB  - The number of patients with non-insulin-dependent-diabetes mellitus (NIDDM) is
      dramatically increasing in Japan and estimated to be 6 million, more than one of
      ten adults. It is well known that more than a half of diabetics are hypertensive.
      Therefore, it is very important to treat hypertension to reduce cardiovascular
      events as well as end-stage renal disease. At first, life style modification such
      as body weight reduction, exercise and restriction of salt and alcohol intake
      will be recommended. Improved glycemic control by such a non-pharmacological
      therapy will lower blood pressure. Recent studies demonstrated that hypoglycemic
      agents improving insulin resistance such as metformin and troglitazone reduce
      blood pressure. If these maneuvers do not lower blood pressure, hypotensive
      medication will be necessary. As a first line therapy, ACE inhibitor, alpha 1
      blocker or Ca-channel blocker will be selected. In diabetics with proteinuria or
      micro-albuminuria, ACE inhibitors will be effective to delay the progression of
      diabetic nephropathy.

PMID- 9284430
TI  - [Exacerbation of atherosclerosis induced by hypertensive and hypercholesterolemic
      states--potential mechanisms and therapeutic implications].
AB  - Several experimental studies suggest many similarities between the effects of
      hypertension and hypercholesterolemia on the arterial wall. Both hypertension and
      hypercholesterolemia have proinflammatory effects on the artery. An increased
      production of oxygen-free radicals leads to increased transcription of redox
      sensitive genes, which increases the expression of vascular cell adhesion
      molecule-1 (VCAM-1) in the endothelium, resulting in increased recruitment of
      monocytes to the endothelium. The oxidative stress on the arterial wall may occur
      in both hypertension and hypercholesterolemia, therefore a synergistic reaction
      between hypertension and hypercholesterolemia may play a role in the
      atherosclerotic process as common causal mechanisms. Among therapeutic strategies
      to protect the vascular injury in both hypertensive and hypercholesterolemic
      state, future research should include direct attack on these common mechanisms.

PMID- 9284431
TI  - [Antihypertensive therapy of patients with cerebrovascular disease].
AB  - In the acute phase of the stroke, it must be prudent to reduce blood pressure
      (BP) because the rapid reduction might cause the exacerbation of the perfusion
      pressure to the brain. The target BP level should be higher than the level of
      primary prevention as the blood pressure regulatory function is disturbed in
      acute phase. In chronic phase, BP should be reduced so slowly through the several
      months so as not to cause the ischemia of the brain by rapid reduction of BP.
      However, the optimal target BP level should be the same degree as the primary
      prevention level as far as the speed of reduction is taken into consideration.
      The several large scale trials, are now in progress to determine the optimal BP
      level for the secondary prevention in the patients with prion stroke.

PMID- 9284432
TI  - [Antihypertensive therapy and heart diseases].
AB  - The one of the most important goal of antihypertensive therapy is to prevent and
      improve the hypertensive heart disease including cardiac hypertrophy and ischemic
      heart disease. The regression of cardiac hypertrophy by treatment reduce the risk
      of cardiovascular events. ACE inhibitor (ACEI) may be the most powerful among
      antihypertensive agents to regress hypertrophy. Ca-antagonist and ACEI can
      improve the impaired coronary flow reserve by microvascular circulation.
      Recently, the evidences have been accumulated that the release of nitric oxide
      (NO) from the coronary artery of hypertension is reduced. "TREND" study proved
      that ACEI can improve this decreases in the clinical study. For the heart
      failure, ACEI is a effective drugs, and Ca-antagonist and beta-blocker also have
      been getting good results.

PMID- 9284433
TI  - [Do angiotensin converting enzyme and calcium channel blocker intervene in the
      progression of renal disease besides by lowering systemic hypertension?].
AB  - Systemic hypertension is accompanied by various renal diseases. Lowering of blood
      pressure is widely recognized effective for slowing further decline of renal
      function. Angiotensin converting enzyme inhibitor (ACEI) and calcium channel
      blocker (CCB) have recently emerged as antihypertensive drugs endowed with
      renoprotective action directed specifically to the kidney. Improvement of
      glomerular hypertension which is more remarkably observed in ACEI than in CCB, is
      thought to be a factor responsible for renoprotection. Although this effect is
      widely shown in experimental models, consensus has not yet been reached as to
      whether this effect as well as the therapeutic efficacy are really exerted in
      various clinical settings other than diabetic nephropathy.

PMID- 9284434
TI  - [Pregnancy induced hypertension].
AB  - Hypertension remains a leading cause of perinatal morbidity and mortality.
      Classification of the hypertensive disorders of pregnancy is 1) preeclampsia
      eclampsia, 2) chronic hypertension, 3) chronic hypertension with superimposed
      preeclampsia-eclampsia. Preeclampsia is characterized by the triad of
      hypertension, proteinuria, and edema but these findings are not specific.
      Although the etiology and pathogenesis of preeclampsia remain unknown, several
      factors such as abnormalities in prostaglandin systems, in coagulation process,
      derangements of the endothelium and so on. Management of preeclampsia is bed
      rest, aspirin administration, antihypertensive agents (beta-blockers,
      hydralazine, alpha-methyldopa) would be used for reduction of blood pressure.

PMID- 9284435
TI  - [Structure and function of symporter and antiporter].
AB  - Structure and function of symporters and antiporters which utilize Na+ as the
      coupling cation are briefly reviewed. The SGLT is an Na+/glucose symporter
      present in animal cell membranes. So far, five isoforms of the SGLT (1 to 5) have
      been found in various tissues. The Me1B is an Na+/galactoside symporter present
      in membranes of enteric bacteria. Regions or amino acid residues of these
      symporters which are important for substrate recognition or cation recognition
      have been identified. Furthermore amino acid substitutions in the SGLT1 of
      glucose-galactose malabsortion families have been identified. Regions and amino
      acid residues which are important for the function of the Na+/H+ antiporters (or
      exchangers) which extrude H+ (in animal cells) or Na+ (in bacterial cells) have
      been also identified.

PMID- 9284436
TI  - [Application of porous bioceramics for a hybrid type artificial liver system].
AB  - Biocompatible porous ceramic carrier was applied for culture of rat hepatocytes.
      Using composit sinters of hydroxyapatite (HAP) and beta-tricalcium phosphate
      (TCP) as culture carriers, freshly harvested rat hepatocytes were cultured.
      Adhesiveness of fibroblast L-929 cells on various TCP-HAP carriers showed that
      the composition of 20%-TCP and 80%-HAP is the most preferable for supporting
      tissue cultures. Hepatocyte function was evaluated by production rates of albumin
      and urea and consumption rate of glucose. The time-dependent variations of the
      hepatocytes functions suggest that the porous TCP-HAP carrier was effective for
      supporting three dimensional tissue structure.

PMID- 9284437
TI  - [Three-dimensional positron emission tomography imaging system and its
      application for medical use].
AB  - Current positron emission tomography is capable for three dimensional data
      acquisition and reconstruction (3D PET). The main advantage of 3D PET is its
      detectability for lower tracer concentrations. The images by a 3D PET have better
      signal to noise ratios compared to those by conventional 2D PET. This point is
      especially important for the studies of distributions of ligands for
      neuroreceptors such as F-18 FDOPA and C-11 YM-01951, since these ligands show low
      accumulation in brain. Reduction of scanning time is useful as well for patients
      are permitting extended scanning periods

PMID- 9284438
TI  - [Gene transfer using adeno-associated virus (AAV) vectors].
AB  - Adeno-associated virus (AAV) is a non-pathogenic, replication defective
      parvovirus. In the absence of helper adenovirus, AAV stably integrates into a
      defined region of human chromosome 19. Because of these unique properties,
      recombinant AAV is considered to be an attractive vector for human gene therapy.
      It has been demonstrated that AAV vectors are capable of efficient transduction
      of various types of cells including hematopoietic cells and post mitotic neuronal
      cells. We have recently developed a new strategy for large scale preparation of
      high titer AAV vectors by using packaging cell lines and sulfonated cellulose
      column chromatography. This new strategy may be important for further development
      of gene therapy using AAV vectors.

PMID- 9284439
TI  - [Recent progress in the research field of nuclear receptors].
AB  - In the research field of nuclear receptors, the studies on the protein factors
      which interact with the steroid hormone receptors and regulate the
      transcriptional activity, and on the alpha and beta isoforms of glucocorticoid
      receptor have been in great progress. The include "intermediary Factors" such as
      RIP140, TIF-1, for the AF-2 which contribute to ligand-dependent transactivation
      function of the receptors. ARA70 which specifically interacts with androgen
      receptor was also cloned recently. Informations obtained from steroid hormone
      receptor knockout-mice experiments can also be available for the estrogen,
      glucocorticoid, and progesterone receptors. Furthermore, there have been more
      than sixty orphan receptors identified in these eight years, including HNF,
      Ad4BP, DAX-1, and nur77/NGFIB, some of which are mutation target genes of human
      congenital diseases.

PMID- 9284440
TI  - [A study of gastroesophageal reflux by 24-hour esophageal pH monitoring in
      patients with bronchial asthma].
AB  - To evaluate the incidence of abnormal gastroesophageal reflux in patients with
      bronchial asthma and the influence of drug therapy on the gastroesophageal
      reflux, we investigated the gastroesophageal reflux patterns using an ambulatory
      24-hour esophageal monitoring in 25 healthy volunteers and 58 asthmatics. All the
      patients were stable conditions at the time of the study. Bronchodilator therapy
      was continued, if necessary along with steroid inhalation and xanthines. Compared
      with healthy volunteers, the asthmatics had significantly greater esophageal acid
      exposure time, more frequent reflux episode, and longer single reflux time. About
      70% of asthmatics had abnormal gastroesophageal reflux. Asthma medications were
      not associated with the incidence of abnormal gastroesophageal reflux. However,
      asthmatics receiving beta(2)-stimulants therapy (n = 27) had significantly
      greater esophageal reflux exposure time than those not receiving (n = 31). Our
      study suggested that most asthmatics have abnormal gastroesophageal reflux
      unrelated to asthma attack or asthma medications and that beta(2)-stimulants used
      in asthmatics may worsen gastroesophageal reflux.

PMID- 9284442
TI  - [A case of ulcerative colitis with minute gastric cancer and intraductal
      papillary adenoma of the pancreas].

PMID- 9284441
TI  - [Partial splenic embolization for the treatment of liver cirrhosis with
      hypersplenism: assessment of clinical response and liver function].
AB  - We have evaluated the efficacy of partial splenic embolization (SE) in the
      treatment in 10 cirrhotic patients with marked hypersplenism. The mean infarction
      rate of the spleen was 84%. The change of spleen size, peripheral blood cell
      counts and liver function tests after SE were investigated during 3 years, and
      also 10 cirrhotic patients without SE were followed as control. The residual
      spleens after SE did not enlarged except 1 case with 65% infarction rate of the
      spleen. In these cases, the SE led not only to a sustained increase in both
      platelet and white blood cell counts but also to a significant improvement of
      hepatic function tests (hepaplastin test, total cholesterol and albumin) during
      observation period. On the other hand, these parameters tended to decrease in
      control patients without SE. This study suggests that SE performed with a high
      infarction rate of spleen is an useful therapy for hypersplenism in cirrhosis.

PMID- 9284443
TI  - [A case of preduodenal portal vein diagnosed concomitantly with malrotation of
      the intestine].

PMID- 9284444
TI  - [A high CEA level in a case of Cronkhite-Canada syndrome, showing decrease by
      prednisolone treatment].

PMID- 9284445
TI  - [A common bile duct foreign body migrated from a war wound].

PMID- 9284446
TI  - [A case report of primary biliary cirrhosis with autoimmune hemolytic anemia].

PMID- 9284447
TI  - [A case of primary biliary cirrhosis associated with fatty liver following
      delivery].

PMID- 9284448
TI  - [A case of drug-induced liver injury due to bukuryo-in-go-hange-koboku-to].

PMID- 9284450
TI  - Computational tools for structure-based ligand design.

PMID- 9284449
TI  - [Two step therapy for education of Helicobacter pylori].

PMID- 9284451
TI  - Homeodomain-type DNA recognition.

PMID- 9284452
TI  - Orientational order determination by internal reflection infrared spectroscopy.
AB  - PATIR-FTIR spectroscopy is a powerful technique for the determination of
      molecular order in thin films such as supported lipid membranes, but it relies on
      electromagnetic theory which is incomplete and potentially misleading. A complete
      derivation of the current theory for two, three and four phase system has been
      reported. The two phase and thin film approximations most commonly used in
      practice have been shown to represent the thickness-dependent expressions from
      which they are derived with a high degree of accuracy. However, these expressions
      are based on the macroscopic behavior of dielectric materials, and may not be
      accurate when applied to microscopic circumstances. The potential error
      introduced is qualitatively and quantitatively significant. Further experimental
      and theoretical work is needed to verify the accuracy of this theory, or to
      refute and refine it. This effort to do this is warranted by the power and
      increasing popularity of the technique.

PMID- 9284453
TI  - Nucleic acid crystallography: a view from the nucleic acid database.
AB  - What are the future directions of the field of nucleic acid crystallography?
      Although there have been many duplex structures determined, the sample is still
      relatively small. This is especially true if one wants to derive enough
      information about the relationships between sequence and structure. Indeed, there
      are data for all the possible 10 dimer steps, but for some steps it is very
      limited. If the structural code resides in trimers or tetrad steps then there is
      simply not enough data to do meaningful statistical analyses. So the first
      direction that needs to be explored is the determination of more structures with
      more varied sequences. The other noticeable thing about the data is the shortness
      of the strands. While it is probably true that attempts to crystallize very long
      sequences will not meet with success, the idea of crystallizing sequences
      engineered to fit together via sticky ends such as has been done for the CAP-DNA
      complex (Schultz et al., 1990) should give data about the behavior of much longer
      stretches of DNA. The question of the effects of environment on the structure of
      DNA continues to be a very important one to address since DNA is rarely alone.
      The preliminary data we have analysed from the current sample shows that the
      conformation of some steps are very sensitive to packing type. Numerous studies
      of the hydration around DNA shows that there is a real synergy between the
      hydration structure and the base conformation. More data will allow further
      quantitation of these observations. RNA structure is the next very exciting
      frontier. The emerging structures of duplexes with internal loops, the two
      hammerhead ribozyme structures and the group I intron ribozyme have given us a
      glimpse of the complexity and elegance of this class of molecules. With the
      technology now in place to allow the determination of the structures of these
      molecules, the expectation is that now we will see a large increase in the number
      of these structures in the NDB.

PMID- 9284454
TI  - What is the problem with high transporters?

PMID- 9284455
TI  - Have we underestimated the importance of fluid balance for the survival of PD
      patients?

PMID- 9284456
TI  - Serum magnesium and end-stage renal disease.

PMID- 9284458
TI  - Searching for evidence-based medical practice.

PMID- 9284457
TI  - Noncompliance in peritoneal dialysis patients.

PMID- 9284459
TI  - Measuring compliance with prescribed exchanges in CAPD and CCPD patients.
AB  - OBJECTIVE: To measure compliance with prescribed exchanges in continuous
      ambulatory peritoneal dialysis (CAPD) and continuous cycling peritoneal dialysis
      (CCPD) patients using inventories of home dialysis supplies; to determine the
      reliability of the ratio of measured to predicted creatinine (M/P) in predicting
      compliance with prescribed exchanges; to determine the effects of the ingestion
      of performed creatine on the excretion of creatinine. DESIGN: A prospective
      analysis. SETTING: A university dialysis center. PATIENTS: Twenty patients on
      home peritoneal dialysis (PD). MEASUREMENTS: An inventory of supplies during two
      home visits over a 4-8 week interval determined the number of PD exchanges
      performed. This number was divided by the number of exchanges prescribed for the
      period to determine the percent compliance. Three consecutive days of the
      dialysate and urine were measured with all food consumed recorded during those
      days. M/P creatinine ratios and dietary protein intake (DPI) for each day were
      calculated. RESULTS: Of the patients tested, 8/20 (4%) were found to be
      noncompliant with the prescribed number of exchanges based on the home visits
      inventories, performing a mean of 75% of their exchanges. There was no
      significant difference in the M/P creatinine ratios of compliant and noncompliant
      patients, nor were the M/P ratios distributed differently for compliant and
      noncompliant patients. The M/P ratios did not vary significantly over the past 3
      days. There was no correlation between the measured creatinine on a given day and
      the DPI for the same day. CONCLUSION: Based on assessment of the patient's
      inventory, 40% of the patients studied were noncompliant with their prescribed
      exchanges, indicating this is a serious and common problem in PD patients. The
      M/P creatinine ratio is not a predictor of compliance in PD. We suggest that use
      of home visit inventories to assess compliance in PD patients.

PMID- 9284460
TI  - Compliance with CAPD prescription is good.
AB  - OBJECTIVE: To determine compliance with continuous ambulatory peritoneal dialysis
      (CAPD) prescription. DESIGN: In the first part of the study, we examined the
      deliveries of dialysate to our CAPD patients (n = 67) between 1992 and 1995 and
      compared these to the CAPD prescription. In the second part of the study, we
      performed two inventory checks in a cohort of patients (n = 26) in one urban
      Canadian center. Compliance was defined as using more than 90% of prescribed
      dialysate. RESULTS: Based on dialysate deliveries, 95% of our CAPD patients were
      compliant. Based on home inventory checks, 12% of patients were noncompliant.
      CONCLUSIONS: Compliance with CAPD prescription is remarkably good in our patient
      population. These data contrast with American data and could partially explain
      differences in mortality rates for CAPD patients between the two countries.

PMID- 9284461
TI  - Measurement of serum ionized magnesium in CAPD patients.
AB  - OBJECTIVE: To evaluate the magnesium status of continuous ambulatory peritoneal
      dialysis (CAPD) patients using a new method for assessing the level of the
      ionized fraction of serum magnesium. DESIGN: Serum ionized magnesium was measured
      in CAPD patients using the ion-selective electrode for Mg2+. SETTING: The
      Dialysis Unit of Tampere University Hospital. PATIENTS: Twenty-six patients on
      CAPD (age: 21-81 years, mean 54 +/- 16 years; duration of CAPD: 3-52 months, mean
      13 months), and 26 sex- and age-matched healthy controls. RESULTS: Both serum
      ionized magnesium (0.73 +/- 0.11 mmol/L vs 0.56 +/- 0.07 mmol/L, p < 0.001) and
      total magnesium (1.11 +/- 0.22 vs 0.81 +/- 0.08 mmol/L, p < 0.01) were higher in
      CAPD patients than in sex- and age-matched controls. The ionized magnesium
      fraction of total magnesium was slightly lower in dialysis patients in spite of
      the fact that 16/26 patients had serum albumin less than 36 g/L. Hypermagnesemia
      (mean serum ionized magnesium 0.78 +/- 0.10 mmol/L) was observed in the 13 of 26
      patients with 0.75 mmol/L Mg2+ dialysate; those with lower magnesium dialysate
      (Mg2+ 0.50 mmol/L in 10/26 and Mg2+ 0.25 mmol/L in 3/26) had mean serum ionized
      magnesium at the upper normal margin (0.69 +/- 0.10 mmol/L). CONCLUSION: In CAPD
      patients with Mg2+ 0.5-0.75 mmol/L in their dialysis fluid, both serum ionized
      and total magnesium concentrations were higher but the ionized/total magnesium
      ratio was lower than in healthy control subjects. Use of ion-selective electrodes
      to measure ionized magnesium may be a more useful methodology than measuring
      total magnesium in the evaluation of magnesium status of CAPD patients, because
      it is not influenced by hypoalbuminemia or increased complexed fraction of
      magnesium often present in dialysis patients.

PMID- 9284462
TI  - Divergent effects of hemodialysis and continuous ambulatory peritoneal dialysis
      on cardiac diastolic function.
AB  - OBJECTIVE: To investigate the effects of dialysis procedures on cardiac diastolic
      function. DESIGN: Comparative, nonrandomized matched pair study. SETTING:
      Nephrology and cardiology departments at a university hospital. PATIENTS: Thirty
      four patients on hemodialysis (HD) (n = 17) and continuous ambulatory peritoneal
      dialysis (CAPD) (n = 17), matched by sex, age, duration of dialysis treatment,
      and presence/absence of diabetes. MEASUREMENTS: Cardiac function was estimated by
      means of M-mode, two-dimensional, and spectral Doppler echocardiography, and
      results were statistically evaluated by means of univariate and multivariate
      analytical procedures. RESULTS: Although not statistically significant, trends
      towards differences between the two patient groups were detected for left
      ventricular mass (p = 0.083) and parameters of diastolic function (p = 0.079).
      These differences in left ventricular performance and diastolic function between
      HD and CAPD patients were also evident when calculating Spearman rank correlation
      coefficients. Left ventricular mass and diastolic function were closely
      correlated to each other in all dialysis patients. Moreover, by means of a
      multivariate analytical procedure (Hotelling T-square test), diversities in
      diastolic function between the two patient groups could be clearly established (p
      = 0.037), with more impaired diastolic function in HD patients. In addition,
      cardiac performance was shown to depend to a certain extent on hemoglobin
      concentration. CONCLUSION: Clear differences in diastolic function and cardiac
      performance were evident between CAPD and HD patients. From the data of our pilot
      study, it may be speculated whether decrease of left ventricular mass could be
      beneficial for the improvement of diastolic function and cardiac hemodynamics in
      dialysis patients.

PMID- 9284463
TI  - Technique failure in peritoneal dialysis and its impact on patient survival.
AB  - OBJECTIVE: To determine the frequency and causes of continuous ambulatory
      peritoneal dialysis (CAPD) technique failure and its effect on patient outcome.
      DESIGN: Retrospective study of CAPD technique and patient outcome. SETTING:
      Teaching hospital renal unit. PATIENTS: All 221 patients commencing CAPD over a
      14-year period. OUTCOME MEASURES: Outcomes assessed included patient survival and
      technique survival (with change to hemodialysis being considered as technique
      failure). RESULTS: CAPD failure occurred in 46 patients, with a CAPD technique
      survival of 93%, 73%, and 63% at 1, 3, and 5 years after start of treatment.
      Peritonitis was the major cause of technique failure. CAPD system had no effect
      on technique survival, despite the lower peritonitis rate in patients using Y
      connection systems. Overall patient survival was 91%, 72%, and 53% at 1, 3, and 5
      years after start of treatment, with increasing age and diabetes being associated
      with a worse outcome. There was a high early mortality after CAPD failure, with
      an actuarial survival of only 61% 1 year later. CONCLUSION: Failure of CAPD is an
      important problem, with peritonitis being the major cause, either directly, or
      indirectly by the later effects of damage to the peritoneal membrane with loss of
      dialysis adequacy. The high mortality in the period following CAPD failure
      warrants careful monitoring of patients during this phase, along with efforts to
      optimize correctable factors such as nutrition, adequacy of the new form of
      dialysis, and treatment of residual sepsis.

PMID- 9284464
TI  - Continuous flow-through peritoneal dialysis (CFPD): comparison of efficiency to
      IPD, TPD, and CAPD in an animal model.
AB  - OBJECTIVE: To determine whether continuous flow-through peritoneal dialysis
      (CFPD), a treatment schedule in which peritoneal dialysate is infused
      continuously into one part of the abdomen (over the liver) and is drained from a
      distant part of the abdomen (the pelvis), can provide greater clearance than
      continuous ambulatory peritoneal dialysis (CAPD), tidal peritoneal dialysis
      (TPD), or intermittent peritoneal dialysis (IPD). DESIGN: A prospective study
      comparing four schedules of peritoneal dialysis in the awake, normal dog, using
      glucose clearance as a substitute for urea clearance. METHODS: We placed two
      chronic dialysis catheters into the abdomen of anesthetized dogs (with
      intraperitoneal portions of fluted or miniature column-disc design). On
      successive days, with the dogs awake and prone, we performed peritoneal dialysis
      for 4 hours with 1.5% dialysate according to one of four schedules, each with 2 L
      maximum intraperitoneal volume: CFPD (unidirectional flow at an average of 3.6
      L/hr), IPD (2 L/hr), TPD (average of 3.6 L/hr, 1 L residual volume), and CAPD (2
      L/4 hr). Glucose and urea clearances were calculated from blood and peritoneal
      concentrations and dialysate flow rates. RESULTS: Stabilized glucose clearances
      (from 60 to 240 minutes) averaged 11 +/- 5 mL/min for IPD, TPD, and CFPD, and 5
      +/- 2 mL/min for CAPD. However, glucose clearances of CFPD were 13 +/- 6 mL/min
      when the intraperitoneal volume was maintained at 800-100 mL, and 16.5 +/- 6
      mL/min when flow rate was 6 L/hr. Urea clearances were twice the measured glucose
      clearances. CONCLUSION: When CFPD is performed with an appropriate
      intraperitoneal volume and flow, it is the most chemically effective method of
      peritoneal dialysis in removing small molecules like urea.

PMID- 9284465
TI  - Reduced glucose degradation products in bicarbonate/lactate-buffered peritoneal
      dialysis solutions produced in two-chambered bags.
AB  - OBJECTIVES: The aims of the current study were: (1) to determine the effects of
      peritoneal dialysis (PD) solutions at different glucose concentrations on the
      growth of cultured cells; (2) to determine whether a bicarbonate/lactate-based
      solution, as a result of the configuration of its components during heat
      sterilization in a two-chambered bag, was lower in glucose degradation products
      than a corresponding lactate-based PD solution; and (3) to determine whether
      lower glucose degradation corresponded to a decreased inhibition of cell growth.
      DESIGN: Growth inhibition of cells exposed to lactate-based PD solutions at three
      different glucose concentrations was determined. Bicarbonate/lactate-based and
      lactate-based solutions at high glucose concentration (3.86%) were further
      analyzed for presence of glucose degradation products and inhibition of cell
      growth. METHODS: Cell growth was determined by neutral red uptake, measured by
      optical density at 540 nm. Glucose degradation to acetaldehyde or fructose was
      determined by gas chromatography-mass spectroscopy and high-performance liquid
      chromatography. RESULTS: Only 3.86% glucose lactate-based PD solution caused
      significant inhibition of cell growth (p < 0.05). The heat-sterilized,
      bicarbonate/dlactate-based solution (3.86% glucose) had lower levels of fructose
      and acetaldehyde than a conventional heat-sterilized, lactate-based solution with
      the same glucose concentration. Growth of cultured cells exposed to the
      bicarbonate/lactate-based solution was significantly improved (p < 0.05) over
      growth in the conventional solution. CONCLUSIONS: The bicarbonate/lactate-based
      solutions, manufactured and heat-sterilized in two-chambered bags, were lower in
      glucose degradation products than that corresponding lactate-based PD solutions,
      and demonstrated improved in vitro biocompatibility as measured by the growth of
      cultured cells.

PMID- 9284466
TI  - Daily exposure to dialysis fluid results in changes in peritoneal transport.
AB  - OBJECTIVE: To study the effects of daily infusion of peritoneal dialysis fluids
      on peritoneal transport characteristics. DESIGN: Twenty-four rats were randomly
      divided into three groups: group A, daily infusions of 20 mL 3.86% glucose
      dialysis function for 10 days (8 rats); group B, daily infusions of 1.36% glucose
      dialysis solution for 10 days (8 rats); group C, no daily infusion, the control
      group (8 rats). Twenty-four hours after the last infusion, a 4-hour dwell study
      using 25 mL 3.86% glucose dialysis solution with frequency dialysate and blood
      samples was performed in each rat. Radio-labeled human albumin (RISA) was added
      to the solution as an intraperitoneal volume marker. EXPERIMENTAL ANIMALS: Twenty
      four male Sprague-Dawley rats (300 g) were used. MAIN OUTCOME: Fluid and small
      solute (glucose, urea, sodium, potassium, phosphate, and urate) transport
      characteristics were evaluated. RESULTS: After 10 days of exposure to dialysis
      fluid, the fluid absorption rate increased in the 3.86% dialysate group compared
      to the other groups (p < 0.05). The clearance of RISA to plasma (an estimation of
      lymphatic absorption), and the absorption of glucose were significantly increased
      in the two experimental groups compared to the control group but there was no
      difference between the two experimental groups. The dialysate/plasma ratio for
      urea, potassium and urate, and the sieving coefficient for phosphate and urate
      were significantly higher in the 3.86% dialysate group compared to the other two
      groups, but there was no significant difference between the 1.36% dialysate group
      and the control group. The clearances of sodium and potassium were significantly
      lower in the 3.86% dialysate group compared to the control group. CONCLUSION: Our
      results suggest that (1) daily infusion of dialysis fluid into the peritoneal
      cavity may increase peritoneal lymphatic absorption: (2) daily infusion of 3.86%
      glucose dialysate may increase peritoneal transport for small solutes.

PMID- 9284467
TI  - Higher membrane permeability predicts poorer patient survival.

PMID- 9284468
TI  - Pneumoperitoneum and pneumomediastinum in a CAPD patient with peritonitis.

PMID- 9284469
TI  - Streptococcal versus Staphylococcus epidermidis peritonitis in CAPD. A
      comparative study.

PMID- 9284471
TI  - Persistent eosinophilic peritonitis associated with fungal infection cured by
      resection of external Tenckhoff catheter: a case report.

PMID- 9284470
TI  - Limited systemic absorption of intraperitoneal ceftizoxime in a patient with
      Serratia marcescens peritonitis.

PMID- 9284473
TI  - Eosinophilic peritonitis in CAPD: treatment with prednisone and diphenhydramine.

PMID- 9284472
TI  - Shedding of soluble interleukin-6 receptor during peritonitis in patients on
      CAPD.

PMID- 9284474
TI  - Treatment of Fusarium peritonitis in a peritoneal dialysis patient.

PMID- 9284476
TI  - Preventing infection with Staphylococcus aureus in CAPD.

PMID- 9284475
TI  - Posthysteroscopy Candida glabrata peritonitis in a patient on CAPD.

PMID- 9284477
TI  - Flavimonas oryzihabitans peritonitis in CAPD.

PMID- 9284478
TI  - Discrepancy between measured and PD ADEQUEST-calculated albumin loss.

PMID- 9284479
TI  - Kt/V is a better indicator of adequacy than weekly creatinine clearance in CAPD.

PMID- 9284481
TI  - Dialysis adequacy and high transporters.

PMID- 9284480
TI  - Unusual complications of a polyurethane PD catheter.

PMID- 9284482
TI  - Literature. July-August 1997.

PMID- 9284483
TI  - Nursing application: patient compliance.

PMID- 9284484
TI  - Development of a preferential relationship with the mother by the newborn lamb:
      importance of the sucking activity.
AB  - Lambs develop a preferential relationship with their mothers within 24 h after
      birth. In a first experiment, we attempted to determine whether neonatal sucking
      was a potent reinforcer in the establishment of this preference by temporarily
      covering the udders of ewes after parturition. Lambs were assigned to one of
      three treatments: they had free access to the udder (group 1) or were prevented
      from sucking either between birth and 6 h afterward (group 2) or between 12 and
      18 h after birth (group 3). Measurements of cholecystokinin plasma levels at
      birth and at 6 and 18 h showed that all lambs ingested some colostrum when the
      udder was made accessible. When tested in a two-choice test situation at 24 h of
      age, lambs from group 1 spent significantly more time near their mothers than
      near the alien ewes, those from group 2 did not show any discrimination, and
      lambs from group 3 clearly preferred the alien ewes. At 2 days of age, lambs from
      groups 1 and 3 showed a strong preference for their mothers, whereas those from
      group 2 still displayed no preference. In a second experiment, we attempted to
      determine whether sucking also had a reinforcing value in the maintenance of this
      preference. Lambs were assigned to one of three treatments: they had free access
      to the udder (group 1) or were prevented from sucking for 6 h either at birth
      (group 2) or at the age of 3 days (group 3). Lambs from group 2 did not
      discriminate between their own and alien dams when tested at 24 h of age, unlike
      those of groups 1 and 3. When a second test was performed at 4 days of age, all
      the lambs showed a strong preference for their dams. We concluded that sucking
      has strong rewarding properties in the establishment of a preferential
      relationship with the mother by the lamb. On the other hand, the maintenance of
      this preference does not rely on sucking as strongly.

PMID- 9284485
TI  - Continuous recording of uneaten food pellets and demand-feeding activity: a new
      approach to studying feeding rhythms in fish.
AB  - The existence of feeding rhythms implies that fish would feed better during their
      preferred feeding phase but reject food at any other time. In the present paper,
      we tested the performance of a new device for continuously collecting and
      detecting uneaten food pellets. The device is basically made of two parts: a
      pellet collector placed just under the feeder and a decanter with a sensor
      attached to the bottom. When a food pellet was not eaten, it was rapidly
      collected and transferred to the decanter, where it was detected while dropping
      by an infrared sensor coupled to a microcomputer. To validate this system, five
      groups of fifteen sea bass, Dicentrachus labrax L., were maintained under natural
      conditions and subjected to a daily feeding cycle (feeding rate = 2.5% of body
      weight) consisting of three meals of one hour duration each (0800-0900 h, 1600
      1700 h and 2400-0100 h). Uneaten pellets together with demand-feeding activity
      were simultaneously recorded. In addition to these test tanks, "natural" demand
      feeding rhythms were also investigated in five groups of sea bass maintained
      under an ad lib self-feeding regime. In the test tanks, when submitted to the
      three meal feeding cycle, sea bass showed clear time preferences for feeding,
      since they fed mostly during the morning and afternoon, rejecting food at night.
      Consequently, the profile of uneaten pellets peaked at night butt remained very
      low during daytime. This diurnal preference for feeding is consistent with the
      almost strict diurnal feeding rhythm found in the sea bass groups under ad lib
      self-feeding. These results revealed the usefulness of this device in estimating
      food utilization and its potential application in nutritional and
      chronobiological studies in fish.

PMID- 9284486
TI  - Plasma galanin immunoreactivity in the rat after swimming.
AB  - The purpose of our experiment was to study plasma immunoreactive galanin in the
      rat after swimming. Four groups of rats were used. At rest, one group was studied
      after an intravenous injection of D-glucose while another group received a
      corresponding saline injection. The two remaining groups, treated respectively
      with glucose and saline, were investigated after a 30-min swimming session. After
      30 min of rest in their respective cages, or after swimming, the animals were
      anesthetized for immediate blood sampling. The main observation was that plasma
      galanin was higher after swimming than after rest only in glucose-treated rats,
      in the vena cava (11.82 +/- 2.90 vs. 5.05 +/- 1.65 pM) and the portal vein (15.75
      +/- 3.74 vs. 6.58 +/- 1.75 pM). Both saline- and glucose-treated groups had a
      significant increase of plasma norepinephrine from rest to swimming in the vena
      cava. A decrease of plasma insulin was observed in the portal vein of exercised
      glucose-treated rats, while plasma glucose was higher in the portal vein of this
      group. In conclusion, after swimming, plasma galanin level was increased only in
      glucose-treated rats. A significant correlation was also observed between plasma
      galanin and glucose (r = 0.69, p < 0.01), suggesting that the presence of glucose
      is necessary to induce galanin liberation during exercise.

PMID- 9284487
TI  - Computer programs to analyze brain electrical activity during copulatory pelvic
      thrusting in male rats.
AB  - Two microcomputer programs have been developed to simultaneously record and
      analyze the brain electrical activity: multiple unit activity (MUA) and
      electroencephalogram (EEG), and the accelerometric signals generated in relation
      to the pelvic thrusting that performs the male rat during the copulatory
      responses of mount, intromission, and ejaculation. CAPTUMUL is a program allowing
      the on line capture of the different signals and the further off line
      delimitation of the brain signals occurring in exact temporal relation with the
      accelerometric record of motor responses. The ANAMUA program allows the off line
      analysis of the neuronal firing rate in MUA records at different discrimination
      levels according to the amplitude of the neuronal spikes, and compare these data
      in various behavioral situations. The use of these programs provides a way of
      correlating in time the changes of brain electrical activity occurring in animals
      in free-movement with the brief motor events of copulation as well as with other
      behaviors (i.e., genital grooming, sniffing, running, walking). Advantages of
      this software include the recording of sequential events, a better and rapid
      handling of data and a reliable method to analyze the MUA with different
      discrimination levels according to the amplitude of the neuronal spikes.

PMID- 9284488
TI  - Meal composition and its effect on postprandial sleepiness.
AB  - Drowsiness is a commonly experienced phenomenon following food ingestion. The
      present two experiments were designed to assess separately the effects of a solid
      meal compared to a liquid meal and to an equal volume of water, and the effects
      of meal constituents (high-fat, high-carbohydrate, or mixed meal) on objective
      postprandial sleep latencies. Ten normal male subjects participated in each
      study. Both studies used identical protocols, differing only in the meals the
      subjects were fed. All subjects underwent a pre-meal baseline nap at 1600 hours.
      At 1700 hours, subjects consumed a test meal. Naps followed at 1730, 1800, 1900,
      and 2000 hours. Sleep onset latency was determined by standard polysomnographic
      measures. In both studies, a one-way repeated-measures ANOVA procedure revealed
      no significant difference in sleep latencies among the meal conditions for the
      nap at 1600 hours. However, for the postprandial naps at 1730, 1800, and 2000
      hours, the solid meal demonstrated a significant decrease in postprandial sleep
      latency compared with an equivalent volume of water (control). No significant
      differences in sleep latency were found between the food constituents. Results
      indicate that in contrast to a liquid meal, a solid meal produces a decrease in
      sleep onset latency when compared to an equivalent volume of water. Further, it
      was demonstrated that meal constituents have no effect on postprandial
      sleepiness.

PMID- 9284490
TI  - Pentylenetetrazol kindling changes the ability to induce potentiation phenomena
      in the hippocampal CA1 region.
AB  - The present study describes changes of response enhancement of hippocampal field
      potentials in slices of kindled rats using different methods to induce long
      lasting potentiation. Eight-week-old male Wistar rats were subjected to
      pentylenetetrazol (PTZ) kindling induced by intraperitoneal injection of 45 mg/kg
      once every 48 h until the occurrence of seizure stages 4-5. Eight to 12 days
      after the last kindling session, transverse hippocampus slices were prepared and
      maintained in an artificial medium. Evoked-field potentials were recorded in the
      CA1 region upon stimulation of the Schaffer collaterals. Potentiation was
      induced: 1. By moderate tetanic stimulation of the Schaffer collaterals, 2. by
      changing the perfusion medium to 0-magnesium for 30 min, and 3. by changing the
      medium to 4 mM Ca2+ for 7 min. In slices from kindled rats, long-term
      potentiation (LTP) after tetanic stimulation and increase of the evoked potential
      by 0-magnesium were significantly enhanced in comparison to slices from sham
      kindled rats. However, Ca(2+)-induced LTP could not be induced in slices from
      kindled rats. The results support the assumption that PTZ kindling also induces
      lasting changes in the responsiveness of hippocampal structures, expressed as an
      enhanced ability to induce potentiation. An alteration of N-methyl-D-aspartate
      (NMDA) receptor-coupled processes can be assumed. The inability to induce Ca(2+)
      induced LTP points to more complex effects of PTZ, perhaps also on nonNMDA
      coupled ionic channels.

PMID- 9284489
TI  - Basic emotions evoked by odorants: comparison between autonomic responses and
      self-evaluation.
AB  - The present study was designed to analyze the relationship between self-report
      and physiological expression of basic emotions (happiness, surprise, fear,
      sadness, disgust and anger) in response to odorants. 44 subjects inhaled five
      odorants: vanillin, menthol, eugenol, methyl methacrylate, and propionic acid.
      Six autonomic nervous systems (ANS) parameters were simultaneously recorded in
      real time and without interference: Skin Potential (SP), Skin Resistance (SR),
      Skin Temperature (ST), Skin Blood Flow (SBF), Instantaneous Respiratory Frequency
      (IRF) and Instantaneous Heart Rate (IHR). At the end of the recording, subjects
      were instructed i) to identify the odorants roughly II) to situate them on an 11
      point hedonic scale from highly pleasant (0) to highly unpleasant (10); and iii)
      to define what type of basic emotion was evoked by each odorant. In this study,
      the expected affects were aroused in the subjects. Vanillin and menthol were
      rated pleasant, while methyl methacrylate and propionic acid were judged
      unpleasant. Eugenol was median in hedonic estimation. ANS evaluation (each
      autonomic pattern induced by an odorant was transcripted into a basic emotion)
      shows that pleasantly connoted odorants evoked mainly happiness and surprise, but
      that unpleasant ones induced mainly disgust and anger. Eugenol was associated
      with positive and negative affects. Comparison between conscious (verbal) and
      unconscious (ANS) emotions, reveals that these two estimations 1) were not
      significantly different as far as the two pleasant odorants were concerned, 2)
      showed a tendency to be significantly different for eugenol odorant which was
      variably scored on the hedonic axis, and 3) exhibited a significant difference
      for the two unpleasant odorants, for which the corresponding "verbal emotion" was
      mainly "disgust", while the most frequent ANS emotion was "anger". In conclusion,
      these results show quite a good correlation between verbal and ANS estimated
      basic emotions. The main difference concerns anger: while there is a high
      occurrence of this emotion revealed by the analysis of ANS responses, it does not
      appear to be easily expressed through the verbal channel.

PMID- 9284491
TI  - Comparison of rats selectively bred for high and low ethanol intake in a forced
      swim-test model of depression: effects of desipramine.
AB  - This investigation examined if there is a relationship between selective breeding
      for high or low alcohol intake and immobility in a force-swim-test (i.e.,
      "behavioral despair") model of depression. Time spent immobile in a water-filled
      cylinder was measured in the alcohol-preferring (P and nonpreferring (NP) lines
      of rats, and in the high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD)
      lines. Each rat was tested for 2 10-min trials administered 24 h apart, and
      pretreatment with saline or desipramine (10.0 or 20.0 mg desipramine/kg b.wt.
      i.p.) also was evaluated. Drug was administered immediately after Trial 1 and
      again 1 h before Trial 2. When tested without pretreatment in Trial 1 or with
      saline pretreatment in Trial 2, NP rats spent significantly more time immobile
      than did P rats, but no comparable line differences were found when HAD and LAD
      rats were tested. Desipramine pretreatment reduced the time spent immobile in
      rats of the 2 alcohol-nonpreferring lines (i.e., the NP and LAD rats), but had no
      significant effect in rats of the 2 alcohol-preferring lines (the P and HAD
      rats). These findings do not support the hypothesis that there is a functional
      relationship between high alcohol drinking and susceptibility to "behavioral
      despair" as measured by the forced-swim test. The results with desipramine
      suggest that selection for high alcohol intake may be associated with
      insensitivity to desipramine.

PMID- 9284492
TI  - Design variability in web geometry of an orb-weaving spider.
AB  - We studied the effect of several variables (environmental and physiological) on
      web geometry in the garden cross spider Araneus diadematus. Variables were: web
      support, wind, temperature, humidity, and silk supply. All had an effect. The
      spiders generally attempted to fit their webs to the shape of the supporting
      frame (standard, small, vertical, or horizontal). Windy conditions (0.5 m s-1)
      during web construction caused spiders to build smaller and rounder webs, laying
      down fewer capture spirals while increasing the distances between capture-spiral
      meshes. Decreasing temperature from 24 degrees to 12 degrees C caused the capture
      spiral to have fewer and wider spaced meshes, which did not change overall
      capture area but reduced the length of capture-spiral threads laid down.
      Subsequent increase of temperature to 24 degrees C restored the number of meshes
      laid down, but the wider mesh was retained, causing the capture area to be
      increased over initial control values. Decreased humidity (from 70 to 20% rH) had
      the effect of reducing web and capture-spiral size, the latter by reducing mesh
      number while keeping mesh spacing constant. Subsequent increase of humidity to
      control level (70%) restored web and capture area. However, this was achieved by
      laying down capture meshes at larger distances, rather than returning to initial
      mesh numbers. Silk supply also had a strong effect. Webs built in unnaturally
      rapid succession by the same spider (4 in 24 h when 1 is the norm) became
      sequentially smaller, had fewer radii, shorter capture spirals, and were wider
      meshed.

PMID- 9284493
TI  - Facial and autonomic responses to biological and artificial olfactory stimuli in
      human neonates: re-examining early hedonic discrimination of odors.
AB  - Responses of awake and asleep 3-day-old human neonates were recorded to the
      presentation of artificial (vanillin, butyric acid, formula milks) and biological
      (breast milk, amniotic fluid) odorants matched on subjective intensity and
      trigeminal dimensions. The responses included behavioral (facial and oral
      movements) and autonomic (respiration, differential skin temperature) measures.
      The neonates reacted with significant facial and respiratory changes to low
      concentrations of olfactory stimuli during the various behavioral states. The
      analysis of olfacto-facial configurations revealed that behavioral markers of
      disgust (nose wrinkling, upper lip raising) discriminated between some odors
      judged as being pleasant and unpleasant by adult raters (vanillin vs. butyric
      acid). However, although some early predisposition to process the affective
      significance of stimuli may be suggested, no convincing evidence was obtained
      that neonates discriminated the hedonic valence of odors within the same
      perceptual space as adults. Finally, neonates evinced a differential pattern of
      respiratory responding to the presentation of milk odors according to the mode of
      feeding (breast vs. bottle feeding), suggesting that early olfactory
      discrimination may be mediated by stimuli with high ecological salience.

PMID- 9284494
TI  - Lengthening of circadian period in hamsters by novelty-induced wheel running.
AB  - Phase shifts resulting from nonphotic events can be accompanied by sizable
      changes in the free-running period. This study examined the relationship between
      tau changes and phase shifts produced by confining Syrian hamsters to a novel
      running wheel in the mid-subjective day. Both phase shifting and tau lengthening
      were higher in animals that made a high number of wheel turns in the 3 h in the
      novel wheel. Hamsters that ran little during the activity pulse, and did not
      subsequently exhibit either phase shifts or tau lengthening, had low baseline
      activity and long taus before the pulse. However, long taus did not preclude
      hamsters from running in a novel wheel and subsequently phase shifting. This was
      demonstrated by finding the phase shifts after activity pulses in animals whose
      tau had already been lengthened by previous activity pulses in novel wheels. The
      possibility is discussed that feedback from locomotor activity influences the
      period of the clock in hamsters, but it is concluded that, in addition, there
      must be other mechanisms accounting for the relationships between activity and
      tau.

PMID- 9284495
TI  - Insulin responses to a fat meal in hypothalamic microdialysates and plasma.
AB  - In a recent microdialysis study in freely-behaving rats, we observed changes in
      immunoreactive insulin (IRI) in hypothalamic dialysates after a meal of standard
      laboratory chow. These changes did not always parallel plasma insulin variations,
      suggesting a partial independence from peripheral insulin. In the present study,
      we have attempted to assess the profile of medial hypothalamus (VMPH-PVN)
      extracellular insulin and peripheral insulin before and after a fat meal (lard).
      In contrast to the increase we previously observed with chow meals, hypothalamic
      extracellular IRI decreased during the fat meal and fell to 60% 30 min after the
      meal. Plasma insulin levels did not change. The intake of the lard meal, provided
      in unlimited amounts, was much larger in calories than the intake of a chow meal
      under the same conditions. However, when rats were offered a meal of chow after
      they had eaten a meal averaging 6.7 g of fat (61 calories), they immediately
      began eating the chow. Thus, the meal of fat produced no general satiation. On
      the contrary, the rats consumed a second chow meal only after a delay of
      approximately 40 min after the first one. The present data, in conjunction with
      our previous observations with chow fed rats, suggest that the level of
      extracellular hypothalamic IRI may decrease independently of plasma insulin
      levels and may, at least partially, account for the observed lack of satiation.

PMID- 9284496
TI  - Post-trial sleep in old rats trained for a two-way active avoidance task.
AB  - Nine male Wistar rats aged 27 months were trained for a two-way active avoidance
      task and tested for retention the following day. At variance with young adult
      rats, most of which succeed in mastering the task, all old rats displayed a large
      majority of freezing responses throughout the training and the retention
      sessions, thereby confirming the condition of learning impairment of aged rats.
      Comparison of baseline and post-trial sleep indicated the presence of a
      transient, but marked, increment in the average duration and total amount of post
      trial slow-wave sleep followed by waking, and of a decrease in total amount of
      quiet waking. On the other hand, variables of paradoxical sleep and of slow-wave
      sleep followed by paradoxical sleep or by transition sleep did not show
      significant variations. Because these sleep variables are known to undergo
      significant variations in learning in young adult rats, the present data confirm
      that the latter effects are related to memory-processing events rather than to
      nonspecific effects of training. An additional outcome of training consisted in a
      marked post-trial decrement in the number of spike-wave discharges, which are
      known to occur in old rats during periods of quiet waking.

PMID- 9284497
TI  - Effects of pregnancy, sucrose, and various low-protein diets on the eating
      behavior of rats.
AB  - To assess the effects of various low-protein diets on the eating behavior of
      female rats, 280 rats were assigned to one of 20 groups, according to a 5 x 2 x 2
      (Protein Level x Pregnancy x Sugar) design. Each rat was offered one of five
      isocaloric, soy-based diets: 25%, 8%, 4%, 2% or 1% protein diet. The subjects'
      intakes and weights were recorded daily for 3 weeks. Protein content of the diet,
      pregnancy, and the presence of dietary sucrose all had significant effects on
      diet, sucrose, and protein intake. By the third week of the experiment, pregnant
      rats offered 1%, 2% or 4% protein diets consumed significantly less of their diet
      than did their nonpregnant controls, whereas pregnant rats in the 25% protein
      group consumed significantly more of their diet than did nonpregnant controls.
      The eating behavior of the rats offered the 8% protein diet was most affected by
      the presence of dietary sucrose. Pregnant rats in the 8% protein group consumed
      less of their diet than did nonpregnant controls when sucrose was also offered,
      but they consumed more of their diet than did nonpregnant controls when sucrose
      was not offered. A learned food aversion is probably the best explanation for the
      severe reduction of diet intake observed in pregnant rats in all of the 1%, 2%,
      and 4% protein groups, as well as in pregnant rats offered the 8% protein diet
      and sucrose.

PMID- 9284498
TI  - Effects of 30 days of undernutrition on reaction time, moods, and symptoms.
AB  - Few modern studies have addressed the effects of undernutrition on the behavior
      of healthy individuals. This study, conducted as part of a test of a
      nutritionally balanced but calorie-deficient experimental ratio, examined the
      effects of 30 days of undernutrition on healthy, physically active soldiers.
      Tests of reaction time and standardized questionnaires assessing mood and symptom
      parameters (known to be sensitive to nutritional and other factors) were
      administered prior to and following a 30-day field exercise. During the exercise,
      17 soldiers consumed a calorie-deficient, lightweight ration (LW group, 1946
      kcal/day) and 17 consumed a calorie-adequate control ration (FN group, 2782
      kcal/day). Mean energy expenditure for both groups was 3200-3300 kcal/day. There
      were no differences between the two diet groups on any of the measures of
      reaction time, mood, or symptoms after 30 days of ration consumption.
      Additionally, there were no adverse changes in reaction time performance from pre
      to post-testing. Adverse changes in moods and symptoms were seen in both groups
      at the conclusion of the test, possibly because of the rigors of living in the
      field for an extended period of time. This study demonstrates that, in healthy
      individuals, various aspects of mental performance, mood, and symptoms are not
      affected by up to 30 days of moderate undernutrition.

PMID- 9284499
TI  - Bombesin receptor antagonists block the effects of exogenous bombesin but not of
      nutrients on food intake.
AB  - The endogenous, meal-contingent release of bombesin (BN)-like peptides is thought
      to contribute to the termination of a meal. In the following experiments the
      potency of BN receptor antagonists to attenuate the ability of nutrients to
      suppress food intake was tested. First, the effectiveness of BN receptor subtype
      antagonists was verified by testing their ability to block the effects of
      exogenous BN on food intake. Rats were administered intraperitoneal (i.p.)
      injections of either saline or 0.1 mg/kg [D-Phe12,Leu14]BN (binds both GRP and
      NMB receptors), [D-Phe6]BN(6-13) ethyl amide (binds GRP > NMB), and cyclo-SS-octa
      (BIM-23042; binds NMB > GRP). Five minutes later rats were administered 8
      micrograms/kg BN (i.p.) and milk intake was measured. Injections of [D
      Phe12,Leu14]BN and [D-Phe6]BN(6-13) ethyl amide reliably attenuated the ability
      of BN to suppress milk intake whereas BIM-23042 was ineffective. The results show
      that the antagonists were behaviorally effective and that exogenous BN may exert
      its effects on food intake primarily through the GRP receptor subtype. Next, the
      antagonists were administered either 5 min prior to or 5 min after an
      intragastric nutrient load or no load in both overnight-deprived and nondeprived
      rats, and milk intake was then measured. Stomach loads reduced intake and this
      effect was not attenuated by BN receptor antagonists. Finally, rats were allowed
      to prefeed and the milk was then removed. Rats were then administered a BN
      receptor antagonist (0.1 and 1.0 mg/kg) or saline either immediately after the
      prefeed, 10 min later, or 20 min later. Milk diet was then returned and intake
      was measured. Peripheral injections of the BN receptor antagonist had no effect
      compared to saline on milk intake. Collectively, the results indicate that the
      blockade of peripheral Bn peptide receptors is not sufficient to attenuate the
      safety signals generated by stomach loads or prefeeding.

PMID- 9284500
TI  - Morphine and dextrorphan lose antinociceptive activity but exhibit an antispastic
      action in chronic spinal rats.
AB  - Within 3-4 weeks after spinal transection, morphine-induced antinociception,
      assessed with the tail flick reflex in rats, is profoundly reduced. The cause of
      this decrement is unknown. The present studies were conducted to determine
      whether this phenomenon reflects a general loss in opiate activity or a selective
      decline in opiate antinociception. This was accomplished by assessing the effect
      of morphine on two different responses, the tail flick reflex and the hindlimb
      spasticity that develops in chronic spinal rats. Because excitatory amino acid
      antagonists are also antinociceptive in acute spinal rats, the effect of one such
      drug, dextrorphan, on these two behaviors was also evaluated in chronic spinal
      animals. The antinociceptive and antispastic effect of subcutaneous (6 mg/kg) and
      intrathecal (5 micrograms) morphine injections were assessed in intact and
      chronic (21-28 days) spinal rats, whereas the effect of subcutaneous (25 and 40
      mg/kg) and intrathecal (350 micrograms) dextrorphan was assessed in acute (1 day)
      and chronic spinal rats. The antinociceptive effect of both drugs was
      significantly reduced in chronic spinal animals, relative to saline controls.
      However, each drug treatment produced a significant antispastic effect in the
      same animals, indicating a selective decline in opiate action. This outcome also
      suggests that excitatory amino acid antagonists may be useful as adjunct
      antispastic agents.

PMID- 9284501
TI  - Validation of the feeding test as an index of fear in farmed blue (Alopex
      lagopus) and silver foxes (Vulpes vulpes).
AB  - The reliability and validity of the eating behaviour in the presence of man
      (Feeding test) as an index of fear were assessed in farmed blue (Alopex lagopus)
      and silver foxes (Vulpes vulpes). Repeatability of the Feeding test was good in
      both species. No further habituation occurred after the fourth successive test in
      either species. In addition, the behaviour of both species was independent of the
      person who performed the test. The normal feeding interval, i.e., 24 h, between
      feed deliveries, was long enough to provide reliable results. The presence of a
      cage mate did not influence the blue foxes' response in the Feeding test. A
      significant relationship between the results of the Feeding test and the Tit-bit
      test in both species and between the Feeding test and fearfulness score in silver
      foxes indicate that all these tests measure similar features, most probably
      foxes' fear of humans. Those silver foxes that did not eat in the Feeding test
      had higher base levels of cortisol than the animals that did eat, providing
      further support for the above conclusion. The present study demonstrates that the
      Feeding test is a reliable, i.e., repeatable and free of random errors, and
      fairly valid fear test for blue and silver foxes. The Feeding test seems likely
      to give good results in measuring fear in farmed blue and silver foxes, but
      further investigations will be needed to fully validate it, especially for blue
      foxes.

PMID- 9284502
TI  - Iron stores in professional athletes throughout the sports season.
AB  - Sports anemia provoked by iron deficiency develops slowly and although the
      existence or reality of this condition is under discussion, the ferritin levels
      tend to reduce with sports practice. This paper analyzes the variations of iron
      metabolism, including the organism stores of this metal throughout a sports
      season in a group of professional sportsmen (soccer players) belonging to a team
      of the Spanish First Division. For the determination of the iron stores, a
      computer program has been developed that takes into account the ferritin
      concentrations, hemoglobin, and saturation of transferrin. The results show that
      at the end of the season, when the ferric supplementation, which had been
      performed at the other moments of analysis, was no longer administered the iron
      stores reduced significantly, as well as the serum ferritin concentration,
      without such decreases being considered as a prelatent (grade I) anemia.

PMID- 9284503
TI  - Body temperature and wheel running predict survival times in rats exposed to
      activity-stress.
AB  - The relationship between restricted feeding, core body temperature (Tb), wheel
      running, survival, and gastric erosion formation was examined in female rats
      exposed to activity-stress. Core body temperature and gross motor activity were
      telemetrically monitored in four groups of rats that had free access to running
      wheels and in one group that was not allowed to run on the wheels. Twenty-four
      hours prior to the onset of hypothermia and predicted mortality, different groups
      were left undisturbed, warmed with a heat lamp, denied access to running wheels,
      or euthanized. Length of survival in wheel-running rats varied from 2 to 12 days.
      During the first day of food deprivation, premorbid changes in the variability of
      Tb during the diurnal period and the mean number of wheel revolutions during the
      nocturnal period were strongly predictive of length of survival. Warming rats
      with a heat lamp or preventing rats from ever running on the wheel increased the
      length of survival and attenuated gastric erosion formation. Only rats that were
      warmed had a greater likelihood of survival. Gastric pathology was also reduced
      in rats that were euthanized prior to becoming moribund. Rats that were left
      undisturbed or locked from the running wheel over the last 24 h of testing became
      moribund and had extensive gastric mucosal damage. These results indicate that
      thermoregulatory disturbances induced by restricted feeding and not wheel running
      alone are critical in determining survival and the degree of gastric mucosal
      injury in rats exposed to activity-stress. Results further suggest that
      predisposing factors may put some rats at risk for the development of activity
      stress-induced mortality.

PMID- 9284504
TI  - Appetitive operant behavior and free-feeding in rats exposed to acute stress.
AB  - This study investigated whether appetitive operant food reinforcement or free
      feeding behavior in rats, food-restricted to 85% of body weight, was disrupted by
      exposures to 3 h of restraint stress or by 3 h of restraint plus water immersion
      stress (RWI). Rats were trained under a 3-cycle 10-min time-out-10-min time-in
      fixed-ratio 15 (FR15) schedule of food reinforcement. Free-feeding was measured
      in a 3-cycle 10-min food jar-out-10-min food jar-in test conducted in the operant
      chambers. Three hours of restraint stress did not significantly affect response
      rate or food reinforcement in the operant FR15 task or in the free-feeding
      condition. In contrast, 3 h of RWI completely abolished operant food
      reinforcement and suppressed response rate, whereas free-feeding was
      significantly reduced but not abolished in food-restricted, hungry rats. We
      conclude that acute restraint stress in food-restricted, hungry rats does not
      affect their appetite or motor ability to lever-press for food nor did it affect
      their ability to feed in a free-feeding situation. In contrast, RWI stress may
      have induced a motor impairment, or some other aspect of motivation independent
      of hunger, that disrupted their performance in the operant FR15 task.

PMID- 9284505
TI  - Cyproheptadine produced modest increases in total caloric intake by humans.
AB  - Four male and three female normal-weight research volunteers, participating in an
      18-day residential study, received oral cyproheptadine (4 mg) or placebo at 0930,
      1245, and 1730 hours daily. Food intake, performance, and subjective ratings were
      measured throughout the day. The interaction between cyproheptadine and
      carbohydrate consumption was examined by providing subjects diets that engendered
      varied levels of carbohydrate intake. Three diet conditions were tested for 6
      days each: a regular diet, a low-carbohydrate (high-fat) diet, and a high
      carbohydrate diet. Placebo was given on days 1, 2, 3, and 6, while cyproheptadine
      was given on days 4 and 5 of each diet condition. When subjects received placebo
      and had access to a regular diet, they consumed 2500 kcal/day (59% carbohydrate
      28% fat, 13% protein). Total caloric intake decreased (p < 0.007) when subjects
      received placebo and had access to the low-carbohydrate diet (40% carbohydrate,
      43% fat, 17% protein) and increased (p < 0.056) when subjects received placebo
      and had access to a high-carbohydrate diet (70% carbohydrate, 19% fat, 11%
      protein). Cyproheptadine significantly increased total daily caloric intake by
      20%, to 3000 kcal, only under the regular diet condition. The increase in caloric
      intake was due to an increase in the number of eating occasions without a change
      in eating occasion size. Although subjects consumed more food under the regular
      diet and cyproheptadine condition, cyproheptadine had no effect on the relative
      contribution of macronutrients to total daily caloric intake. There was no
      evidence for a modulation of the food-intake increasing effects of cyproheptadine
      by the macronutrient mix of the available diet. Cyproheptadine also significantly
      altered self-reported mood: compared to placebo, cyproheptadine produced
      significant increases in ratings of "Tired", "Sleepy", "Headache", "Can't
      Concentrate", and "Bad Drug Effect" and decreases in "Alert". Furthermore,
      cyproheptadine produced small decrements in psychomotor task performance.

PMID- 9284506
TI  - Insulin during infancy attenuates insulin-induced hypoglycemia in adult male
      rats.
AB  - To examine whether insulin during infancy affects later glucose regulation, 60
      rat pups of both sexes were injected daily on postnatal Days 9-20 with either
      insulin (2 or 8 U/kg), 2-deoxy-D-glucose (2DG; 200 or 400 mg/kg), or saline. Two
      hours postinjection on Day 15, pups given insulin were hypoglycemic and pups
      given 2DG were hyperglycemic; both groups were normoglycemic at 6 h. The two
      insulin doses produced similar long-term effects, as did the 2DG doses, so doses
      were combined to make single insulin and 2DG groups. On Day 44, baseline plasma
      glucose for rats given insulin or 2DG during infancy was below saline control
      levels (111.3, 114.5, and 120.7 mg/dL, respectively, p < 0.05). On Days 60 and
      62, plasma glucose was assessed 2 h after injection of 3 U/kg insulin; food was
      allowed between the insulin injection and the glucose test on only one of these
      days. When food was present after injection of insulin, the early treatments did
      not influence either amount of food ingested or plasma glucose levels. When food
      was withheld, however, males given insulin before weaning maintained a higher
      plasma glucose than did males given 2DG or saline before weaning (67.4, 40.1, and
      16.4 mg/dL, respectively, p < 0.01); females were unaffected by the early
      treatment. Postweaning body weights did not differ from control values for rats
      given early insulin or 2DG. On Day 72, there were no effects of early treatment
      on plasma insulin, plasma glucose, liver weight, or kidney weight. These results
      suggest that preweaning exposure to insulin attenuates the hypoglycemia of adult
      males given insulin without food.

PMID- 9284507
TI  - Effects of repeated cold stress on feeding, avoidance behavior, and pain-related
      nerve fiber activity.
AB  - The specific alternation of rhythm in temperature (SART), which is defined as
      rapid and frequent changes in the environmental temperature several times within
      the course of a day, produces abnormalities in behavior such as hyperphagia and
      in sensory sensation such as hyperalgesia. As the first step toward understanding
      the mechanisms of these abnormalities, we studied the effects or SART stress on
      ingestive behavior. During the light and dark phases, the animals' food intake
      increased, but their body weight gain decreased. In addition, diurnal variation
      in body weight also decreased. Next, we examined the behavioral and
      electrophysiological effects of SART stress on avoidance behavior by studying the
      rat's avoidance of a noxious stimulus in the form of a footshock. The rats
      demonstrated hyperreactivity; the delay in escaping the footshock was decreased
      by SART stress. The excitability of C-fiber activity, which responds to
      mechanical and thermal stimuli to a single saphenous nerve, was not changed by
      SART stress. This suggests that the hyperreactivity in footshock avoidance and
      the hyperalgesia in pain response induced by SART stress are based on excessive
      emotionality.

PMID- 9284508
TI  - Immunity costs and behavioural modulation in male laboratory mice (Mus musculus)
      exposed to the odours of females.
AB  - In a previous study, male laboratory mice experimentally immunodepressed with
      anti-thymocyte serum (ATS) showed changes in behaviour (aggression, general
      locomotory activity, and sleeping) and testosterone that are consistent with
      decision-making being modulated adaptively with respect to immunocompetence. We
      tested this idea further by repeating the experiment with the addition of female
      odours (soiled sawdust) to the home cages of males following ATS/control
      treatment. We predicted that, in the presence of cues suggesting reproductive
      opportunity, immunodepressed males would trade off potential immunity costs by
      failing to modulate behaviour. This expectation was borne out in that ATS-treated
      mice showed no change in aggression, locomotory activity, mounting, or sleeping
      relative to control animals, and mice overall showed differences in behaviour in
      the expected direction compared with a previous study in which female odours were
      not presented. However, despite the lack of difference in behaviour between ATS
      and control treatments, there was still evidence of a degree of behavioural
      modulation in relation to measures of immunocompetence.

PMID- 9284509
TI  - FOS immunoreactivity after exposure to conspecific or heterospecific urine: where
      are chemosensory cues sorted?
AB  - Female prairie voles (Microtus ochrogaster) typically require an intact
      vomeronasal system and exposure to a chemical signal found in urine from male
      prairie voles to induce uterine growth necessary for reproduction. Urine from
      male mice (Mus musculus) does not contain an effective cue for activation of
      female vole reproduction: after 4 days of exposure to stimuli, voles exposed to
      urine from female or water had still uteri whereas voles exposed to urine from
      male voles had large uteri. The initial response to urine from male voles
      included neuronal activity in the vomeronasal system as indicated by FOS
      immunocytochemistry. Stimuli (urine from a male vole or a male mouse, or water)
      were painted on the nose of naive female voles 1 h before sacrifice. Female voles
      exposed to urine from male voles had more FOS-immunoreactive cells in the
      accessory olfactory bulb than voles exposed to mouse urine or to water. We
      conclude that exposure to urine from male voles stimulates the vomeronasal
      pathway (as measured by FOS immunoreactivity) and induces uterine growth in
      female voles, whereas exposure to urine from male mice (or water) does not. This
      suggests that some degree of functional specificity of the clinical cue is
      determined at or before the accessory olfactory bulb, perhaps in the expression
      of specific receptors within the vomeronasal organ, rather than entirely within
      the central nervous system.

PMID- 9284510
TI  - Preloads of corn oil inhibit independent ingestion on postnatal day 15 in rats.
AB  - The ontogenetic development of postingestive inhibitory control of ingestion by
      an oil preload was examined in preweaning rats. Gastric preloads (5% b.wt) of
      water, mineral oil or corn oil were administered 5 min before a 30-min intake
      test in which pups licked milk from the floor of a test chamber. Preloads of corn
      oil decreased intake significantly compared with preloads of mineral oil or water
      on Postnatal Days 15 and 18, but not on Postnatal Day 12. Because preloads of
      corn oil reduced intake ore than preloads of mineral oil, it is possible that the
      inhibitory effect of corn oil is due to its fats rather than to its oily texture.
      Cholecystokinin (CCK), presumably released from the small intestine, apparently
      mediates part of this inhibitory effect because pretreatment with devazepide, a
      specific CKKA antagonist, significantly reduced the inhibition produced by corn
      oil.

PMID- 9284511
TI  - Taste reception mechanisms in the blowfly: evidence of amiloride-sensitive and
      insensitive receptor sites.
AB  - The role of amiloride in the labellar responses to various taste stimuli in the
      blowfly Protophormia terraenovae was studied with the aim of ascertaining whether
      amiloride-sensitive cation conductances are present in the chemosensory systems
      of insects. Results include that: 1) amiloride has no effect on the "salt" cell
      response to any stimulus; 2) amiloride decreases the "sugar" cell response to
      fructose, but does not affect that to sucrose; 3) the effects of amiloride on the
      responses of the "water" cell and the "fifth" cell are less clearly definable,
      due to the probable superimposition of osmotic mechanisms in the former and the
      poorly known response modalities of the water. In conclusion, amiloride-sensitive
      receptor sites seem to exist also in insects. However, unlike most vertebrates
      investigated, they are principally located in the sugar receptor cell, not on the
      salt cell.

PMID- 9284512
TI  - Demonstration of ejaculation-induced neural activity in the male rat brain using
      5-HT1A agonist 8-OH-DPAT.
AB  - Previous studies from our laboratory indicated that existence of ejaculation
      related neural activation within the circuitry underlying mating behavior in the
      male rat. Clusters of Fos-immunoreactive neurons were present only following
      ejaculations and not after intromissions. However, it was not clear if this
      pattern of neural was specific to ejaculation or a result of summation of sexual
      activity preceding ejaculation. In the present study, the facilitative effect of
      the 5-HT1A receptor agonist 8-OH-DPAT on ejaculatory behavior was used to analyze
      the pattern of Fos immunoreactivity ejaculation preceded by minimal sexual
      activity. Male rats treated with 8-OH-DPAT (0.4 mg/kg) achieved ejaculation after
      a shortened latency and low numbers of mounts and intromissions. Ejaculation
      induced Fos immunoreactivity was present in clusters of neurons in the lateral
      part of the posterodorsal medial amygdala, in two subregions of the posteromedial
      bed nucleus of the stria terminalis, in the posterodorsal preoptic nucleus, and
      in the parvicellular part of the subparafascicular thalamic nucleus. Males that
      ejaculated with the first intromission and were treated with a higher dose of 8
      OH-DPAT (0.8 mg/kg) exhibited similar clusters of Fos-positive neurons in all
      areas except the posterodorsal preoptic nucleus. The results demonstrate the
      existence of a specific ejaculation-related subcircuit within a larger neural
      circuitry involved in male sexual behavior.

PMID- 9284513
TI  - Temporal glucocorticoid treatment: modulation of periodic endometrial responses
      during decidualization and pregnancy in rats.
AB  - The synthetic glucocorticoid, dexamethasone (Dex) was administered subcutaneously
      (1.5 mg/day/rat) in 3-days pretreatment regimens (Days 2-4, 4-6, 6-8, 8-10 and 10
      12) to pseudopregnant rats in which decidualization was surgically induced and to
      pregnant rats. Variability in endometrial growth during decidualization and in
      the fetoplacental homeostasis of pregnancy was assessed at the end of each
      treatment period (Days 4, 6, 8, 10 and 12). During decidualization, endometrial
      growth (wet weight, protein and DNA) displayed significant (p < 0.05) time
      dependent inhibitory profiles which rose steeply from Day 4 to Day 6 and declined
      thereafter to Day 10 in fairly well defined linear patterns. For the endometrial
      enzymes (isocitrate dehydrogenase, alkaline phosphatase and the matrix
      metalloproteinases--72 and 92 kDa), although the inhibitory patterns were
      inconsistent, a Days 6-8 treatment regimen seemed to be critical. By contrast Dex
      treatment induced progressive inhibition in serum progesterone concentrations
      from Day 2, to peak levels by Day 12. This indicates that time-related Dex
      inhibition of endometrial growth appeared not to be progesterone-mediated since
      the endometrial and progesterone inhibitory profiles were not in synchrony. The
      inhibitory effect of Dex under the pregnancy status demonstrated that birth
      potentials, fetal and placental weights, all had similar response patterns which
      rose from Day 4 to Day 8 and then underwent reductions to Day 12. Collectively,
      the results indicate that there was time dependency in growth inhibition by Dex
      at the endometrial and fetoplacental levels. Maximal sensitivity to drug exposure
      essentially coincided with the immediate post-traumal (decidualization) and
      postimplantation (pregnancy) periods.

PMID- 9284515
TI  - Alternate-day wheel access: effects on feeding, body weight, and running.
AB  - For rats access to a running wheel results in a pronounced but temporary
      suppression of feeding. The reasons for the feeding suppression and its temporary
      nature are unclear. The effects of alternate-day wheel access were explored by
      comparing feeding and running in 25 male Sprague-Dawley rats given either no
      wheel access, continuous wheel access, or alternate-day wheel access. With
      alternate-day wheel access food intake was suppressed on wheel days and elevated
      on non-wheel days for the full 32 days of the experiment. Body weight decreased
      on wheel days and showed a large increase on non-wheel days. Acquisition of
      running over days was similar in both wheel groups and plateaued at the same
      level, but running was elevated, compared to continuous-access rats, for the
      first few hours when alternate-day rats were returned to the wheel. These results
      suggest that wheel-induced feeding suppression is not due to the novelty of the
      wheel and that this suppression can be extended by providing periods with no
      wheel access. The temporary nature of feeding suppression in chronic access
      conditions may be due to secondary longer term motivational changes.

PMID- 9284514
TI  - Ovulatory pheromone shortens ovarian cycles of female rats living in olfactory
      isolation.
AB  - McClintock found that female rats living in isolation or in groups synchronized
      their ovarian cycles, and she proposed a two-pheromone mechanism to explain
      synchrony: one pheromone shortens cycles and the other lengthens them. Subsequent
      research revealed that the preovulatory pheromone shortened cycles, whereas the
      ovulatory pheromone lengthened cycles. Schank and McClintock modeled this
      mechanism with computer simulation, assuming variability in sensitivity to
      pheromones during the ovarian cycle, and found that a coupled-oscillator
      mechanism can synchronize cycles, if pheromone sensitivity is highest around the
      time of ovulation. In this paper, we report the effects of pulses of ovulatory
      pheromone on the ovarian cycles of isolated female rats. Donor females were in
      the ovulatory phase of their cycle and recipient females were in olfactory
      isolation except during specified phases of their ovarian cycles. Recipient
      females showed significant shortening in ovarian cycles, with no significant
      variability in sensitivity to the ovulatory pheromone during the ovarian cycle.
      We discuss these conflicting results in terms of the experimental context of
      recipient females and the components and complexities of pheromone signals.

PMID- 9284516
TI  - Testosterone and pupillary response to auditory sexual stimuli.
AB  - Low-, medium-, and high-testosterone subjects listened to four 30-s recorded
      stimuli while a computer system continuously measured their pupil size. The
      stimuli dealt with sex, aggression, and two neutral topics. Subjects dilated more
      to sex than to the other topics. Male and female subjects responded similarly,
      although low-testosterone males did not dilate as long as other subjects to the
      sexual stimulus. Auditory stimuli avoid a brightness artifact associated with
      visual stimuli. Auditory stimuli can be used in a variety of pupillometry
      studies, including studies of ongoing conversation and social interaction.

PMID- 9284517
TI  - Effect of photoperiod on body mass, and daily energy intake and energy
      expenditure in young rats.
AB  - In this experiment we investigate the effect of photoperiod on locomotor
      activity, body mass, food intake, growth efficiency (relationship between body
      mass change and food intake), energy expenditure, and body composition in growing
      Wistar rats. Two groups of animals were subjected to either a long, LD 18:6 (n =
      8) or short photoperiod, LD 6:18 (n = 7), during a period of 190 days after
      weaning. Activity, body mass, food intake, and energy expenditure were measured
      during the study, as well as body composition at the end of the experiment. We
      show that growing rats exposed to short photoperiod (a) have a lower rate of
      weight gain, (b) have similar energy intakes, (c) have lower growth efficiency,
      (d) have lower daily energy expenditure and resting metabolic rate, and (e) gain
      less lean body mass than those exposed to long photoperiods. We suggest that the
      distribution of energy expenditure and food intake over the total 24-h cycle may
      be responsible for the differences in body weight gain between the two
      photoperiods.

PMID- 9284518
TI  - Erection evoked in male rats by airborne scent from estrous females.
AB  - In the presence of inaccessible estrous females, male rats display penile
      erections and associated stereotypic behavior indicative of sexual arousal. The
      effective stimuli for these noncontact erections (NCEs) had not been determined,
      but bedding soiled by estrous females was known to be ineffective. The present
      experiments tested for a potential role for volatile olfactory cues in evoking
      NCE. In Experiment 1, sexually naive male rats were observed for NCEs when tested
      with inaccessible, estrous females, upwind (n = 20) or downwind (n = 20) from
      them under conditions that permitted or prevented visual communication. After
      half the males in each condition had copulatory experience, they were tested
      under the same conditions. In each test, only on male of 20 responded with
      females downwind, whereas about half the 20 males displayed NCEs with females
      upwind, irrespective of barrier type or, in Test 2, of sexual experience.
      Olfactory cues from estrous females were apparently necessary to induce NCE,
      whereas visual and auditory stimuli from estrous were not sufficient to evoke
      NCE, nor did they affect the response to olfactory stimulation. In Experiment 2,
      males were downwind from estrous females (n = 10) or anestrous females (n = 10)
      that were behind opaque barriers and were anesthetized to preclude auditory
      communication. Results indicated that olfactory cues were also sufficient to
      provoke NCE in sexually experienced males. Receptive female rats apparently
      broadcast a volatile pheromone that promotes erection. Pheromones are well known
      to attract potential mates and to act in concert with other stimuli to promote
      mating. However, this is the first mammalian evidence for a volatile pheromone
      acting alone to evoke a sexual fixed-action pattern and, in that sense, acting as
      an airborne aphrodisiac.

PMID- 9284520
TI  - Duration of cyanide-induced conditioned food aversions in possums.
AB  - Learned aversions developed following sublethal ingestion of poisons are reported
      to be long-lived in many pest species. This study aimed to identify the duration
      of bait aversions following poisoning with a common poison (cyanide) used for
      possum control in New Zealand. Groups of possums with bait aversions (following
      cyanide poisoning) were reexposed to the bait (flavoured food) in a 2-choice
      test, at intervals of 1, 3, 6, 12, or 24 months. The relative intakes of the bait
      (used as the measure of bait aversion) did not differ between treatments (0.21,
      0.21, 0.27, 0.32, and 0.20) for the 5 groups, respectively. The effect of
      repeated reexposures to the bait was also tested. The proportion of flavoured
      food eaten was 0.11, 0.19, 0.23, 0.33, and 0.36 for 1 to 5 reexposures,
      respectively. There was a significant increase in intake with repeated exposure.
      Thus, cyanide-induced aversions were strong and lasted for at least 24 months.
      The aversions weakened over several reexposures to the bait, but only for those
      individuals that had weaker initial aversions.

PMID- 9284519
TI  - Effect of amiloride on suprathreshold NaCl, LiCl, and KCl salt taste in humans.
AB  - The purpose of this study was to investigate normal variances in the response
      magnitudes of suprathreshold concentrations of NaCl, LiCl, and KCl salts and
      amiloride on the anterior human tongue. Random equimolar concentrations of salt
      solutions were delivered to spatially matched flow chambers of 20 volunteers at 3
      different sessions. A cross-modal magnitude matching procedure was used to scale
      salt taste-intensity judgments. After each salt test, amiloride (100 microns) was
      delivered for 5 min and the test was repeated. At least-square regression
      analysis of each subjects' function between log molar concentration and log
      response demonstrated that every subject scaled the dynamic range of salts. There
      were no differences in either the mean regression or intercept among the 3 salts.
      Repeated-measures analysis demonstrated a statistical effect of amiloride on the
      before/after difference in the regression (p = 0.02) and intercept (p < 0.0001)
      of NaCl and LiCl functions. Postamiloride NaCl and LiCl coefficient of variance
      of response was increased. Amiloride had no effect on the before/after difference
      in the regression and intercept of KCl power functions or the variance of
      response. The results suggest that, after amiloride, NaCl and LiCl suprathreshold
      salt taste intensities are reduced, but there are individual variabilities of
      reduced intensity that are never completely eliminated.

PMID- 9284521
TI  - Amygdaloid lesion-induced obesity in rats in absence of finickiness.
AB  - Female rats with lesions of the most posterodorsal aspects of the amygdala were
      tested for their reaction to a variety of manipulations of their food and water
      supply. Compared to control animals, the rats with lesions were hyperphagic and
      displayed excess weight gain. However, they did not consume more of a high-fat
      diet or of a sucrose solution than did controls, nor did they consume less than
      controls when their food or water supply was adulterated with quinine or when
      switched from pellets to ground chow. On a fine-powder diet, control animals lost
      weight whereas rats with lesions gained weight. Rats with lesions consumed more
      saline than controls in a two-bottle preference test. These results are
      consistent with those of earlier studies of other species with amygdaloid damage.
      It is concluded that rats with lesions of the posterodorsal amygdala are
      hyperphagic in absence of the marked finickiness that characterizes some other
      brain lesion-induced obesity syndromes.

PMID- 9284522
TI  - Chronic treatment with desipramine: effect on endocrine and behavioral responses
      induced by inescapable stress.
AB  - Inescapable shock (IS) exposure induces behavioral inactivity, related to
      behavioral alterations in subsequent tests (i.e. escape failure during shuttle
      box task). Previous studies have demonstrated that various antidepressant
      treatments administered either before or after IS exposure reversed these
      behavioral deficits. Recently, we demonstrated corticosterone (CS) involvement
      both in inactivity performance during IS and in the number of escape failures in
      a shuttle box task. In the present study, we analyzed the effects of chronic
      desipramine (DMI) treatment administered before or after IS exposure on the
      dynamics of changes in serum CS concentration after both IS and shuttle box task,
      to explore a possible relationship between the hormonal response and the
      reversion of the behavioral induced by DMI. DMI (10 mg/kg intraperitoneally i.p.)
      administered during 6 consecutive days before IS reduced release and inactivity
      induced by this aversive experience. Two days later, when these DMI-treated rats
      were submitted to a shuttle box task, a reduction in CS release and IS-induced
      escape failures were observed as compared with saline-treated rats. Besides, in
      animals without IS experience, the pretreatment with DMI did not modify either
      the pattern of CS secretion or the percentage of escape failures as compared with
      saline-injected rats. On the other hand, CS values of rats treated with DMI
      during 6 consecutive days after IS exposure recovered to resting controls levels
      within 60 min post-shuttle box task, exhibiting fewer escape failures; unlike
      saline-treated, IS-exposed rats, which retained persistently elevated levels of
      CS (during the post-task sampling interval) a showed a high percentage of escape
      failures. Thus, chronic DMI administration before IS attenuated CS secretion and
      prevented the onset and expression of behavioral deficits induced by
      uncontrollable stressors. However, when it was administered after IS, it induced
      an increased negative feedback sensitivity in coincidence with the reversion of
      the IS-induced behavioral deficits.

PMID- 9284523
TI  - The disruption of cell cycle checkpoints by papillomavirus oncoproteins
      contributes to anogenital neoplasia.
AB  - Human cancer are characterized by the failure of cell cycle checkpoints resulting
      in genetic instability. Human papillomaviruses contribute to the development of
      anogenital malignancies because the E6 and R7 oncoproteins from high risk HPV
      types are able to disrupt the integrity of these checkpoints. HPV 16 E7 prevents
      suprabasal cells from exiting the cell cycle, thus increasing the pool of
      replicating cells that are available for additional 'hits'. Cells that suffer DNA
      of chromosome damage are not eliminated because E6 and E7 are able to bypass G1
      and G2 damage-induced checkpoints. The activation, or inactivation, of additional
      cellular genes required for invasion and metastasis may not be a direct
      consequence of the E6/E7 oncoproteins.

PMID- 9284524
TI  - Mechanism of HPV E6 proteins in cellular transformation.
AB  - The E6 protein is a major transforming protein of many types of papillomaviruses.
      Mechanistically, the best characterized E6 proteins are those of the high-risk
      genital HPVs (e.g. HPV-16 and 18 E6), which function, at least in part, by
      inactivating the p53 tumor suppressor protein. Biochemical studies have shown
      that this occurs by targeted degradation of p53, dependent on the E6-AP ubiquitin
      protein ligase. The model that has emerged from E6/E6-AP-dependent p53
      degradation has provided insight into both HPV-associated carcinogenesis and the
      problem of substrate specificity of the ubiquitin system. Several observations
      suggest that the high-risk HPV E6 proteins may also have activities in addition
      to inactivation of p53.

PMID- 9284525
TI  - Interactions of the human papillomavirus E7 protein with cell cycle regulators.
AB  - Human papillomavirus (HPVs) critically depend on the cellular machinery for the
      replication of their genome. Viral replication is restricted to the
      differentiated strata of the skin that are normally growth arrested. Hence, the
      HPVs have developed strategies to subvert cellular growth regulatory pathways and
      are able to uncouple cellular proliferation and differentiation. The HPV E7
      protein can overcome the activity of some cyclin-dependent kinase inhibitors,
      associate with cyclin/cyclin dependent kinase complexes and bind to and
      destabilize the retinoblastoma tumor suppressor protein. These biological
      activities contribute to the carcinogenic potential of the high risk HPV E7
      proteins which are consistently expressed in HPV-positive cervical carcinomas.

PMID- 9284526
TI  - Control of papillomavirus DNA replication and transcription.
AB  - Hallmarks of HPV infection include a restricted tropism for human epithelial
      cells and a viral life cycle tightly linked to the differentiation program of the
      host keratinocyte. This particular viral cycle has hampered the study of the HPV
      vegetative life cycle for decades, due to the lack of suitable in-vitro culture
      conditions. The tissue and differentiation dependence seems to be dictated by
      viral transcription rather than viral DNA replication. Indeed, viral
      transcription is restricted to epithelial cells of human origin, more
      specifically to keratinocytes. In contrast, HPV genomes can replicate in various
      undifferentiated cell lines regardless of their natural permissiveness to
      infection, as long as the viral replication proteins E1 and E2 are expressed.

PMID- 9284527
TI  - Heterogeneity of papillomaviruses.
AB  - The classification of the papillomaviral sequence into types is satisfactory for
      many purposes, but the resulting catalog does not accurately depict the extent of
      diversification of this family of viruses. Phylogenetic and mutational analyses
      reveal that some viral forms are much more ancient than other forms. Episodic
      evolutionary events and zoonotic transmission may have contributed to the overall
      pattern. Convergent evolution appears to be the best explanation for the
      scattered occurrence across the family tree of viruses with high oncogenic risk.
      We look for the determinants of this risk among the less conserved residues of
      the viral E6 and E7 transforming proteins.

PMID- 9284528
TI  - HLA control in the progression of human papillomavirus infections.
AB  - Cellular immunity is likely to be of major importance for the clearance of
      inapparent or overt infections caused by human papillomaviruses (HPVs). The
      highly polymorphic class I or class II human leukocyte antigen (HLA) molecules
      present HPV-derived peptides to cytotoxic (CD8+) or helper (CD4+) T lymphocytes
      bearing specific receptors and condition the immune responsiveness to HPV
      infections. Recent data point to a role of an altered expression of HLA molecules
      in the persistence of HPV-induced cervical premalignant lesions and their
      progression towards invasive carcinoma. Furthermore positive of negative
      associations of certain HLA alleles or haplotypes with cutaneous of cervical
      neoplasias have been found. These observations may have important implications in
      the design of therapy or vaccines aimed at eradicating cervical cancer.

PMID- 9284529
TI  - Papillomavirus-like particles and HPV vaccine development.
AB  - Human papillomavirus-like particles (VLPs), self-assembled after high level
      expression of the papillomavirus L1 virion capsid protein in non-mammalian cells,
      are attractive candidates for a subunit vaccine to prevent genital HPV infection
      and the subsequent development of cervical cancer. In animal studies, purified
      VLPs induce high titers of antibodies against conformational type specific L1
      epitopes. These antibodies neutralize homologous virions in in-vitro assays and
      protect against experimental challenge in several animal models. The encouraging
      results in animals justify the initiation of human trials of HPV VLP-based
      vaccines. Factors to be considered when designing these trials are discussed.

PMID- 9284530
TI  - Short-term exposure to JP-8 jet fuel results in long-term immunotoxicity.
AB  - Chronic exposure to jet fuel has been shown to have adverse effects on human
      liver function, to cause emotional dysfunction, to cause abnormal
      electroencephalograms, to cause shortened attention spans, and to decrease
      sensorimotor speed. Due to the decision by the United States Air Force to
      implement the widespread use of JP-8 jet fuel in its operations, a thorough
      understanding of its potential effects upon exposed personnel is both critical
      and necessary. Exposure to potential environmental toxicants such as JP-8 may
      have significant effects on host systems beyond those readily visible (i.e.,
      physiology, cardiology, respiratory, etc.); e.g., the immune system. Previous
      studies have shown that short-term, low concentration JP-8 exposure had
      significant effects on the immune system, which should have serious consequences
      for the exposed host in terms of susceptibility to infectious agents. If these
      alterations in immune function were long-lasting, it might also result in an
      increased likelihood of development and/or progression of cancer, as well as
      autoimmune disease. In the current study, mice were exposed for 1 h/day for 7
      days to a moderate (1000 mg/m3) and a high (2500 mg/m3) concentration of
      aerosolized JP-8 jet fuel to stimulate occupational exposures. One to 28 days
      after the last exposure the mice were analyzed for effects of the exposure on
      their immune systems. It was observed that decrease in viable immune cell numbers
      and immune organ weights found at 24 h after exposure persisted for extended
      periods of time. Further, JP-8 exposure resulted in significantly decreased
      immune infection, as analyzed by mitogenesis assays, which persisted for up to 4
      weeks post-exposure. Thus, short-term exposure of mice to JP-8 jet fuel caused
      significant toxicological effects on the immune system, which were long-lasting
      and persistent. It appears that the immune system may be the most sensitive
      indicator of toxicological damage due to JP-8 exposure. Such long-term changes in
      immune status may have significant effects on the health of the exposed
      individual.

PMID- 9284532
TI  - Minimizing cancer risk using molecular techniques: a review.
AB  - This review article summarizes molecular markers that can signal enhanced risk of
      cancer and provide clinicians with these clues in order to attempt the use of
      natural and synthetic compounds to intervene in the early precancerous stages of
      carcinogenesis before invasive disease begins. With an aim such as this in mind,
      we have begun to apply molecular techniques based on many research articles to
      look for biomarkers capable of signaling a greater risk of cancer. It is possible
      to attain relatively quick answers by monitoring selected signs and damage in the
      body which provide the environment for abnormal cell growth and differentiation.
      These molecular techniques aim to uncover critical precancerous events taking
      place inside the body and identify measurable biologic flags signaling their
      occurrence. For years now, scientists have understood that the onset of cancer is
      a gradual, step-wise process that may unfold over the course of decades, rather
      than a single, fixed event that can be dated in a pathologist's report.
      Carcinogenesis usually encompasses the prolonged accumulation of injuries at
      several different biological levels and includes both genetic and biochemical
      changes in cells. At each of these levels there is an opportunity for
      intervention-a chance to prevent, slow or even halt the gradual march of healthy
      cells toward malignancy. It is estimated that 75% of cancers are induced by
      chemicals; thus, if exposure to chemicals is avoided, cancer can be prevented.
      Also, depending on the individual's genetic background, the ability to metabolize
      chemicals is different among the population. This means that, "you and I can be
      exposed to exactly the same amount of a chemical," yet our response will differ
      because we metabolize carcinogens differently due to different rates of
      deoxyribonucleic acid (DNA) repair, apoptosis, and mitosis or different levels of
      Phase I and Phase II detoxification enzymes. This, along with a more or less
      efficient immune system, may promote tumor formation or destroy a cancer cell at
      its earliest stage of development. Therefore, measurement of the biologic markers
      such as DNA and protein adducts, DNA damage, programmed cell death, DNA repair
      system, mitosis, gene activation, levels of antioxidants and efficient immune
      function described in this chapter and summarized in Figures 2 and 10, are
      biological clues indicating that the body has been assaulted by toxic (or cancer
      causing) agents. This early identification of biomarkers for special
      vulnerability to the effects of chemicals and detection of selected signs of
      precancerous damage in the body may culminate preventive measures and the saving
      of lives.

PMID- 9284531
TI  - Protection from JP-8 jet fuel induced immunotoxicity by administration of
      aerosolized substance P.
AB  - Chronic exposure to jet fuel has been shown to cause human liver dysfunction,
      emotional dysfunction, abnormal electroencephalograms, shortened attention spans,
      and decreased sensorimotor speed. The United States Air Force has decided to
      implement the widespread use of JP-8 jet fuel in its operations, although a
      thorough understanding of its potential effects upon exposed personnel is
      unclear. Exposure to potential environment toxicants such as JP-8 may have
      significant effects on host physiology. Previous studies in mice have shown that
      short-term, low concentration JP-8 exposure had significant effects on the immune
      system; e.g., decreased viable immune cell numbers, decreased immune organ
      weights, and loss on immune function that persisted for extended periods of time
      (i.e., up to 4 weeks post-exposure). Previous studies have shown that JP-8
      induced pulmonary dysfunction was associated with a decrease in levels of the
      neuropeptide substance P (SP) in lung lavage fluids. It was found that
      administration of aerosolized SP was able to protect exposed animals from such JP
      8 induced pulmonary changes. In the current study, aerosolized SP was analyzed
      for its effects on JP-i induced immunotoxicity in exposed mice. It was observed
      that SP administration could protect JP-8 exposed animals from losses of viable
      immune cell numbers, but not losses in immune organ weights. Further, exposure of
      animals to SP inhibitors generally increased the immunotoxicity of JP-8 exposure.
      SP appeared to act on all immune cell populations equally as analyzed by flow
      cytometry, as no one immune cell population appeared to be preferentially
      protected by SP. Also, SP administration was capable of protecting JP-8 exposed
      animals from loss of immune function at all concentrations of JP-8 utilized (250
      2500 mg/m3). Significantly, SP only needed to be administered for 15 minutes
      after JP-8 exposure, and was active at both 1 microM and 1 nM concentrations.
      Thus, SP administration appears to be a relatively simple and efficient means to
      reverse the immunotoxicity due to hydrocarbon exposure.

PMID- 9284533
TI  - Reproductive and thyroid hormone levels in rats following 90-day dietary exposure
      to PCB 28 (2,4,4'-trichlorobiphenyl) or PCB 77 (3,3'4,4'-tetrachlorobiphenyl).
AB  - Subchronic exposure to the PCB congener 77 (PCB 77) and 28 (PCB 28) was
      previously shown to induce histological changes in the thyroid and in the brain
      biogenic amines levels, suggesting possible effects on thyroid and reproductive
      hormone levels. Thus, the effects of a 90-day dietary exposure to PCB 28 or 77 on
      luteinizing hormone, follicle-stimulating hormone, and testosterone
      concentrations were studied in male rats, as well as the levels of thyroid
      stimulating hormone, thyroxine (T4) and uridine diphosphate-glucuronyl
      transferase (UDP-GT) activity in both genders. Weanling Sprague Dawley rats were
      randomly distributed into groups of 10 rats and were fed, for the next 13 weeks,
      purina lab chow containing 50, 500, 5,000 or 50 000 ppb of PCB 28 or 10, 100,
      1000, or 10 000 ppb of PCB 77. The serum concentrations of T4 were decreased in
      rats of both sexes receiving 1000 ppb or more of PCB 77, and was associated with
      an increased activity of UDP-GT which reached significance only in the females.
      There was a tendency for the highest dose of PCB 28 also to decrease serum T4
      concentrations in the female rats. None of the PCB treatments significantly
      altered gonadotropin, TSH, or testosterone concentrations. These results suggest
      that thyroid functions may be more susceptible or adapt less readily than the
      pituitary gland and the testes to endocrine disruption caused by PCB congeners.

PMID- 9284535
TI  - Possible aluminum content of canned drinks.
AB  - Preliminary analyses by a commercial laboratory demonstrated varying amounts of
      aluminium in a small sampling of canned drinks, which had been stored at 15-20
      degrees C., ranging from < 0.1 to 74 ppm depending on the product and storage
      time. Aluminum foil wrap immersed in several drinks demonstrated varying raters
      of dissolution from nearly zero to 100% over a 7 months periods when stored at an
      incubator temperature of 32-34 degrees C. Should aluminum prove to be of
      significant pathophysiologic consequence, some consideration should be given to
      all possible sources, including canned drinks which are consumed in copious
      quantities. When internal protective coatings are complete and remain intact, the
      cans stored properly and the contents consumed within a reasonable period of
      time, there appears to be little basis for concern about the ingestion of
      aluminum from the consumption of the canned drinks tested, as things now stand.

PMID- 9284534
TI  - Two new cases of liver angiosarcoma: history and perspectives of liver
      angiosarcoma among plastic industry workers.
AB  - In this report of two new cases of liver angiosarcoma (ASL) among plastic
      industry workers, the authors present the history and perspectives of this
      problem. The first cases of ASL have been registered since 1974, and in 1984, the
      European register of angiosarcoma was founded. In this register, 11 cases of ASL
      and one case of haemangiopericytoma have been registered from Croatia, all from a
      single plastics plant near Split. Two new cases of ASL (in retired autoclave
      cleaners, who were exposed to a concentration of 500-1000 ppm vinyl chloride
      monomer (VCM) during the working process) in the same plant are represented. They
      were detected with combined techniques of ASL detection, and both are still
      alive. The diagnoses have been histologically confirmed: one of them was
      surgically treated with segmental liver resection. The appearance of new cases of
      ASL confirms the perspective presented in the last report by the same authors.

PMID- 9284536
TI  - Biochemistry of inflammatory processes and vascular injury. Role of neutrophils:
      a review.
AB  - Possible mechanisms of the participation of neutrophils in inflammation and
      vascular damage are reviewed. The role of chemotaxis, adhesion, and neutrophil
      endothelium interaction are considered. Specific attention is paid to the action
      of neutrophils (PMNs) in inflammation sites which can be caused by the
      interaction between PMN-generated proteinases and oxygen metabolites.

PMID- 9284538
TI  - Kinetic manifestations of structural self-organization for the components of the
      pyruvate dehydrogenase complex. A mathematical model.
AB  - The structure-function organization of mammalian pyruvate dehydrogenase complex
      (PDC) is considered. The linear size of the complex components in relation to the
      size of their fragments and mean distances between potentially active sites are
      estimated. A kinetic model for the complex with core subunits divided into
      conformational classes characterized by their different activities is discussed.
      The kinetic features of this model are compared with the features of the model
      for the core subunits not divided into classes. Curves are described for the
      activity of PDC versus time for various activities of the kinase and the
      phosphatase as dependent on their binding to more or less active core subunits.
      The results show that spatially distributed multiple active sites in the multi
      enzyme complex can drastically change their full activity in time without any
      marked changes in the rate constants of the elementary reaction steps due only to
      spatially changed reaction pathways. A new type of regulation discussed for PDC
      reveals unusual regulatory abilities for complexes of this family.

PMID- 9284539
TI  - Immunoenzyme assessment of human apoB-lipoprotein binding to immobilized receptor
      of low density lipoproteins. 1. Preparation of anti-receptor monoclonal
      antibodies.
AB  - The preparation and properties of V5 monoclonal antibody to low density
      lipoprotein receptor (LDL-receptor) from bovine adrenal cortex membranes are
      described. The monospecific V5 antibody recognizes the LDL-receptor (the only
      protein with molecular mass of 140 kD) in bovine adrenal cortex membranes. V5
      antibody fails to compete with human low density lipoproteins (LDL) for binding
      to the LDL-receptor. After absorption in standard 96-well polystyrene plates, V5
      antibody efficiently binds the affinity-purified LDL-receptor from the solution
      and the subsequent binding of the LDL-receptor with human LDL was determined
      using peroxidase-labelled antibodies to apolipoprotein B. The LDL-receptor
      immobilized by V5 antibodies is suggested for use in studies on the binding of
      human lipoproteins to the LDL-receptor.

PMID- 9284541
TI  - Effects of vitamin D3 and ecdysterone on free-radical lipid peroxidation.
AB  - Free-radical-induced lipid peroxidation was studied in vivo by measuring
      chemiluminescence of tissues from vitamin D-deficit animals before and after
      peroral administration of low-molecular-weight biological steroids vitamin D3
      (cholecalciferol) and ecdysterone. The kinetics of lipid chemiluminescence in
      model systems in vitro were determined in blood serum and microsomal and
      mitochondrial fractions of the liver. Vitamin D3 (cholecalciferol) and
      ecdysterone displayed antiradical properties; the latter was more potent in this
      respect. Oxidation of lipids by hydroxyl groups contained in ecdysterone can
      account for its antiradical effect. Ecdysterone and D3 may cause antiradical
      effects through the same mechanisms.

PMID- 9284540
TI  - Immunoenzyme assessment of human apoB-lipoprotein binding to immobilized receptor
      of low density lipoproteins. 2. Binding of isolated lipoproteins.
AB  - The receptor of low density lipoproteins (LDL-receptor) from bovine adrenal
      cortex membranes was immobilized in standard 96-well polystyrene plates using
      monoclonal V5-antibodies to the LDL-receptor. The binding of the immobilized LDL
      receptor with human low density lipoproteins (LDL) and very low density
      lipoproteins (VLDL) was determined using peroxidase-labelled antibodies to human
      apoB. The value of Kd for the interaction of LDL with the immobilized LDL
      receptor for 40 samples of LDL was found to be from 5 to 20 micrograms apoB per
      ml. The immobilized LDL-receptor failed to bind LDL modified by acetylation or
      malonic dialdehyde, while the binding of non-modified LDL to the immobilized LDL
      receptor was inhibited in the presence of EDTA, which is known to be specific for
      the interaction of LDL with the LDL-receptor. Unlike LDL, VLDL were more variable
      in the binding to the LDL-receptor. The value of Kd for the interaction of VLDL
      with the LDL-receptor for 40 samples of VLDL was found to be from 0.5 to 10
      micrograms apoB per ml. Thus, the described method is suggested to study the
      interaction of apoB-containing lipoproteins with the LDL-receptor.

PMID- 9284542
TI  - Interaction of oligonucleotides with barrier fluid proteins.
AB  - Affinity modification of proteins was used to study their interaction with
      oligonucleotides barrier fluids. Several proteins of saliva and tears were shown
      to undergo affinity modification during incubation with an alkylating derivative
      of deoxyribooligonucleotides. In tears, such proteins were lactoferrin,
      immunoglobin G and lysozyme; in saliva, immunoglobulin A and lysozyme. The data
      showed that the affinity for oligonucleotides decrease in the order lactoferrin >
      lysozyme > immunoglobulin A > immunoglobulin G. The binding of reactive
      oligonucleotide derivatives with the proteins was competitively inhibited by
      polyanions, such as oligonucleotides of various nucleotide compositions, single
      stranded and double-stranded DNA, heparin, and dextran sulfate. Interactions
      between oligonucleotides and proteins can strongly affect the metabolism of
      oligonucleotides and their ability to permeate biological barriers.

PMID- 9284543
TI  - Kinetic analysis of enzymatic hydrolysis of ATP in human and rat blood serum.
AB  - Kinetic analysis of enzymatic hydrolysis of 14C- or 3H-labelled ATP was performed
      in the blood of healthy men donors and male Wistar rats. Nonspecific phosphatases
      were paralleled in blood serum by specific enzyme ATPase which is capable of
      dephosphorylating exogenous ATP in cooperation with other serum nucleotidases
      ultimately to adenosine. APparent Michaelis-Menten constant (Km) and maximal
      velocity (Vmax) values for rat serum ATPases are 68 +/- 7 microM and 7.0 +/- 0.3
      nmoles ATP/mg protein per h, respectively. ATPase from human blood serum was
      characterized by lower respective Km and Vmax values: 39 +/- 5 microM and 2.5 +/-
      0.2 nmoles ATP/mg protein per h. Activity of serum ATPase was decreased in the
      presence of membrane ecto-ATPase inhibitors PPADS and RB2, whereas the Na,K
      ATPase inhibitor ouabain did not exert any inhibitory action on the measured
      enzyme activity.

PMID- 9284545
TI  - Oxidation of exogenous formaldehyde in methylotrophic and nonmethylotrophic yeast
      cells.
AB  - Nonmethylotrophic (Candida maltosa and Saccharomyces cerevisiae) and
      methylotrophic (Hansenula polymorpha) yeast cells acidified their incubation
      media in the presence of formaldehyde. This was associated with the release of
      formate. We studied the formaldehyde-dependent production of formic acid and the
      enzymatic properties of these strains grown on media containing various carbon
      sources. The acidifying potential was considerably lower in formaldehyde
      dehydrogenase-deficient cells of mutant strains of H. polymorpha. The rates of
      acidification by C. maltosa and S. cerevisiae depended on the activity of their
      nonspecific aldehyde dehydrogenases. We suggest that accumulation of formate by
      yeast cells incubated in the presence of formaldehyde is caused by the total
      activity of formaldehyde dehydrogenase and nonspecific aldehyde dehydrogenase in
      methylotrophic yeasts or aldehyde dehydrogenase only in nonmethylotrophic yeasts.
      This is probably an additional mechanism for detoxification of formaldehyde.

PMID- 9284546
TI  - Langmuir-Blodgett films of cytochrome P450scc and its complex with adrenodoxin.
AB  - Langmuir-Blodgett films prepared from cytochrome P450scc and its complex with
      adrenodoxin have been prepared and studied. Adrenodoxin was preliminarily
      selectively modified with fluorescein isothiocyanate and the effect of this
      modification on the interaction with cytochrome P450scc was studied. Using
      selectively modified adrenodoxin the ratio of the proteins in the film was found
      to be 1 mole of adrenodoxin per 2 moles of cytochrome P450scc. Langmuir-Blodgett
      films were also prepared from adrenodoxin-reductase and it was shown that this
      flavoprotein is transferred to the substrate as an apo-protein. It is also shown
      that the adrenodoxin-binding region of cytochrome P450scc is exposed to the
      subphase under all pressures in the interval studied. The relationship between
      the orientation of cytochrome P450scc-adrenodoxin complex in monolayers on the
      water-air interface and the pressure produced at the interface at the moment of
      monolayer formation was found. Our data are in excellent accordance with ideas on
      the molecular organization of cytochrome P450scc in the inner adrenocortical
      membrane and allows the use of this approach to model membrane structures
      containing cytochrome P450.

PMID- 9284547
TI  - Effect of lipid peroxidation products and antioxidants on the formation of
      probucol radical in low density lipoproteins.
AB  - Effects of antioxidants and products of lipid peroxidation on hemin-induced
      formation of probucol radical in low density lipoproteins (LDL) from human plasma
      were studied by EPR-spectroscopy. Suppression of lipid peroxidation in LDL by
      probucol and other antioxidants (ascorbate, 6-O-palmitoylascorbate, and ubiquinol
      10) prevents the formation of probucol radical. However, ubiquinol-10 stimulates
      the formation of probucol radical during advanced stages of LDL oxidation.
      Because the concentration of probucol radical depends on lipid hydroperoxide
      contents in LDL, the interaction of lipid hydroperoxides with hemin can result in
      the formation of probucol-oxidizing radical intermediates and ubiquinol-10 is a
      mediator of this process.

PMID- 9284544
TI  - Isolation and characterization of myeloperoxidase from leukocytes of rat
      peritoneal fluid.
AB  - Myeloperoxidase (MPO) was isolated from rat peritoneal leukocytes with a yield of
      51% and A430/A280 = 0.75 - 0.80, and its physicochemical properties were studied.
      The molecular weight of the MPO is about 150 kD. The MPO was assayed for amino
      acid content. We used substrate mixture containing phenol, 4-aminoantipyrine, and
      H2O2 to detect 10(-10) M of the enzyme. The MPO was localized in rat blood
      neutrophils using polyclonal anti-MPO antibodies and secondary fluorescein
      isothiocyanate-labeled antibodies. Immunofluorimetric assay (IFMA) was developed
      for quantitative measurement of the MPO. The MPO and leukocytes can iodinate BSA
      using NaI or thyroxine as the source of iodine.

PMID- 9284548
TI  - Photochemical reactions of nitrosyl hemoglobin during exposure to low-power laser
      irradiation.
AB  - Relaxation of blood vessel walls is one of the physiological effects induced by
      visible radiation. This effect is similar to the endothelium-derived relaxation
      (based on endothelium-derived relaxing factor, EDRF) and depends on the presence
      of nitric oxide donors. We assumed that nitric oxide hemoglobin (HbNO) might
      participate in the mechanism of this phenomenon and investigated the
      photochemical reactions using low-power He-Cd (441.6 nm) and He-Ne (632.8 nm)
      lasers. It was found that in the presence of oxygen the He-Cd laser but not He-Ne
      laser induced a photolytic decrease of the HbNO EPR signal amplitude by 25-35%.
      Using optical absorption measurements, we showed that methemoglobin was formed
      during irradiation. The comparison of the kinetics of this process and the
      irreversible reduction of paramagnetic centers suggest that the laser radiation
      leads to dissociation of the heme-NO complexes, but not to oxidation of the heme
      iron. In the absence of oxygen the photodissociation effect did not exceed 5-10%
      and was reversible. We suppose that this finding can be explained by fast
      reassociation of NO with unligated Hb. The EPR spectrum of iminonitroxide was
      observed upon irradiation of HbNo with nitronyl nitroxide in a vacuum, suggesting
      the formation of free NO. Thus, our experiments confirm that NO-hemoglobin can
      reversibly dissociate and release free NO during exposure to He-Cd laser
      radiation.

PMID- 9284549
TI  - Effect of UV-irradiation of rat liver nuclei on structural transitions and
      fractionation of the chromatin.
AB  - The effect of UV-irradiation on the chromatin fractionation from DNase I-treated
      rat liver nuclei by solutions with different concentration of magnesium cations
      and ionic strengths has been investigated. Comparative analysis of the
      biochemical parameters of five fractions isolated from irradiated and non
      irradiated nuclei has shown marked changes in the amounts of DNA, RNA, and
      proteins and in the protein composition. UV-Irradiation induces the dose
      dependent transition of some chromatin from the S3 and S4 fractions into the
      insoluble P4 fraction. Chromatin content in fractions soluble in media with high
      concentrations of magnesium ions (S1 and S2) does not change on irradiation.
      Decrease in extraction of many proteins after UV-irradiation of both nuclei and
      preliminary isolated fractions as a consequence of exposure of the nuclei to UV
      light may be the result of DNA-protein cross-linkage. A profound effect of UV
      irradiation on stabilization of chromatin macrostructure in its condensed regions
      was observed.

PMID- 9284551
TI  - Compounding of premigration trauma and postmigration stress in asylum seekers.
AB  - Unauthorized immigrants arriving in Western countries increasingly are being
      subjected to stringent restrictions while their residency claims are assessed.
      The present study was a investigation of premigration exposure to organized
      violence and postmigration stressors in 40 individuals seeking asylum who were
      attending a community welfare center in Sydney, Australia. Almost 80% reported
      exposure to premigration trauma such as witnessing murders, having their lives
      threatened, being separated from family members, and brainwashing; 25% had been
      tortured. Asylum seekers reported a marked decline in socioeconomic status.
      Common ongoing sources of severe stress included fears of being repatriated,
      barriers to work and social services, separation from family, and issues related
      to the process of pursuing refugee claims. More than one third had problems
      obtaining health services in Australia--the same number who reported similar
      difficulties in their home countries. Although based on a selective and
      culturally heterogeneous sample, the results suggest that salient aspects of the
      asylum-seeking process may compound the stressors suffered by an already
      traumatized group.

PMID- 9284550
TI  - DNA-protein cross-links in leukocytes of mice induced by Zn, Cd, and Pb.
AB  - A single subdermal injection of CdCl2 or Pb(CH3COO)2 results, together with
      remarkable changes in the blood cell pattern, in increased DNA-protein cross
      links in mouse leukocytes in 24 h; after 15 days the DNA-protein cross-linking
      returned to the initial level. In contrast, after injection of ZnSO4 a high level
      of DNA-protein cross-links is retained during the whole observation period (15
      days). In the studied range of doses the formation of DNA-protein cross-links is
      proportional to the logarithm of the dose.

PMID- 9284552
TI  - Masculinity, femininity, and Hispanic professional men's self-esteem and self
      acceptance.
AB  - Research suggests that in the United States, Hispanic professional women's self
      esteem is affected by their unique challenge of balancing U.S. majority cultural
      values with their own, more family-oriented ethnic values. In the present study,
      the effect of this ethnic minority/majority cultural differential on U.S.
      Hispanic men's self-esteem was investigated. Differences in self-esteem, self
      acceptance, masculinity, and femininity among U.S. Hispanic professional men, non
      Hispanic professionals, scientists, college students, and clients seeking
      counseling were examined. Masculinity scores were significantly higher for
      Hispanic professional men than for all other groups of men, and self-acceptance
      scores were significantly lower for Hispanic professional men that for non
      Hispanic professionals and students.

PMID- 9284553
TI  - Anger and depressed affect: interindividual and intraindividual perspectives.
AB  - The relation between anger and depressed affect was examined with both
      interindividual and intraindividual analyses. Seventy-seven undergraduate
      students completed the Beck Depression Inventory (Beck, Ward, Mendelson, Mock, &
      Erbaugh, 1961) and kept a psychological diary for 10 consecutive days. The diary
      included questions dealing with felt anger and expressed anger, and several
      measures of depressed affect. Only one of four correlational analyses between the
      number of days on which students reported feeling angry and aggregate measures of
      depression was significant. However, intraindividual analyses revealed that days
      on which students reported feeling angry were also days on which they reported
      higher levels of depressed affect. The tendency to attribute the cause of angry
      feelings to one's own actions was positively related to depressed affect. The
      tendency to inhibit expression of anger was positively related to the measure of
      depression.

PMID- 9284555
TI  - The structure of attitudes toward persons who are deaf: emotions, values, and
      stereotypes.
AB  - The relative effects of affect, cognition, and stereotyping on attitudes toward
      persons who are deaf were studied, Respondents (N = 175) were initially asked to
      list terms of phrases that described (a) a typical persons who is deaf, (b) the
      feelings the respondent experienced when thinking of a typical person who is
      deaf, and (c) beliefs about how a typical person who is deaf either facilitates
      of blocks cherished values held by the respondent. Then, each respondent
      evaluated as positive or negative each of the terms or phrases he or she wrote
      down. The relative effects of personality variables and structural variables on
      prejudicial attitudes were also assessed. Affect and past experience figured
      prominently in respondents' attitudes toward people who are deaf. Explanations
      for these findings and the implications of these results for prejudice formation
      and reduction were explored, especially in light of the passage, implementation,
      and enforcement of the Americans with Disabilities Act.

PMID- 9284554
TI  - A preliminary analysis of the perceived risks of misusing multiple substances,
      trait anxiety, and approval motivation.
AB  - In a sample of college undergraduates, perceptions of the risks associated with
      the misuse of substances such as alcohol, cigarettes, and marijuana were
      evaluated, and the correlations of risk ratings with trait anxiety and approval
      motivation were examined. The results indicated (a) a temporally stable,
      hierarchical ordering of risk means that ranged from illicit to licit substance
      pairs; (b) a string negative correlation between perceived risk means and
      corresponding standard deviations, suggesting that greater variability was
      associated with lower perceived risk; (c) small to small/moderate correlations
      between high risk ratings and trait anxiety; and (d) small to small/moderate
      correlations between risk ratings and approval motivation. These findings provide
      a first approximation of young adults' perceptions of the possible risks involved
      in the misuse of multiple substances and suggest that such perceptions are not
      confounded by dispositional anxiety of by social desirability response bias. The
      results discussed in light of their implications for alcohol and drug education.

PMID- 9284556
TI  - Highly polymorphic microsatellite loci in the colonial ascidian Botryllus
      schlosseri.
AB  - Five mircosatellite loci are characterized for the colonial ascidian Botryllus
      schlosseri. Within one population from Monterey, California, these loci have 3 to
      17 alleles, observed heterozygosities from 0.40 to 0.63, expected
      heterozygosities from 0.52 to 0.84, and an overall paternity exclusion rate (QT)
      of 0.78. Three of the five loci demonstrated Mendelian patterns of inheritance in
      laboratory crosses. The size distribution of alleles suggests that most allelic
      diversity within these loci is generated by single-step and less frequently
      multistep mutations. However, several alleles may also have been generated by
      single based insertions or deletions. Mutation rates for the five microsatellite
      loci are less than 1 x 10(-2) per generation. Because or their highly polymorphic
      nature, these loci should prove useful for exploring issues of identity, kinship,
      population structure, and phylogenetics.

PMID- 9284558
TI  - Sulfur-oxidizing symbionts have not co-evolved with their hydrothermal vent tube
      worm hosts: an RFLP analysis.
AB  - A fine-scale phylogenetic comparison was made among the symbionts of different
      genera of hydrothermal vent tube worms. These included Riftia pachyptila and
      Tevnia jerichonona, which inhabit sites along the east Pacific Rise, and Ridgeia
      piscesae from the Juan de Fuca Ridge. An analysis of restriction fragment length
      polymorphism (RFLP) was employed using three symbiont-specific gene probes:
      eubacterial 16S rRNA, RuBPC/O Form II, and ATP sulfurylase (recently cloned from
      the Riftia symbiont). Results indicated that all of the symbionts from the three
      different hosts were conspecific and the Riftia and Tevnia symbionts were
      indistinguishable over and 1800-km range. Significantly, this indicates that the
      symbionts have not co-evolved with their respective hosts, which are known to
      belong to separate families. This study strongly supports the conclusion that the
      symbionts are acquired de novo by each generation of juvenile tube worms from a
      common source in the surrounding sea water.

PMID- 9284557
TI  - Cyclins in a dinoflagellate cell cycle.
AB  - The dinoflagellates are distinct eukaryotes in having and extranuclear spindle
      and permanently condensed chromosomes. These cytologic features implicate special
      adaptations to the molecular mechanisms of cell cycle control. We have
      demonstrated the presence of cyclin-box-containing polypeptides in
      dinoflagellates by immunoblotting using peptide-generated antibodies. We
      identified four major cyclin-box-containing polypeptides. The cell cycle dynamics
      of these polypeptides were also investigated in synchronized populations, using a
      newly developed method. Of the four major cyclin-box-containing polypeptides
      detected, a triplex with apparent molecular weight of 75 kDa did not change
      appreciably during the cell cycle. For two other cyclin-box-containing
      polypeptides with apparent molecular weights of 50 and 65 kDa, we observed an
      early expression in the cell cycle, with the level accumulating and eventually
      being degraded on the exit of mitosis. At least on cyclin-box-containing
      polypeptide (50 kDa) was also observed in a protein complex bound to p13suc1
      beads. The bound complex head associated histone kinase activity. Variation of
      this activity corresponded well with the periodic expression of the 50-kDa cyclin
      box-containing polypeptide during the cell cycle of Crypthecodinium cohnii. This
      demonstrates the presence of cyclins and cyclin-dependent kinases in
      dinoflagellates.

PMID- 9284559
TI  - Conservation of the myoglobin gene among Antarctic notothenioid fishes.
AB  - We determined the myoglobin cDNA sequence for seven Antarctic notothenioid fish
      species. These data identify mutations in the myoglobin gene for Champsocephalus
      gunnari and Pagetopsis macropterus, two icefish species that lack detectable
      quantities of the polypeptide but express myoglobin mRNA. a third species lacking
      myoglobin polypeptide, Chaenocephalus aceratus, is devoid of myoglobin mRNA and
      accordingly failed to produce myoglobin products on polymerase chain reaction
      (PCR) amplification. Myoglobin cDNA sequences were highly conserved among the
      species the express the protein, particularly in the coding region. Sequence
      variation among the myoglobin-expressing channichthyid species was 2.0% to 2.9%
      in the coding region and 2.6% to 3.3% over the entire cDNA. The same extent of
      variation, 1.6% to 3.2% in the coding sequence and 2.8% to 3.7% overall, was
      observed between the icefishes and more distantly related, red-blooded
      nototheniid species. The two species expressing mutant myoglobin mRNA, C. gunnari
      and P. macropterus, exhibited the highest degree of sequence variation among the
      fish myoglobins examined. Drift in the myoglobin sequence in these two species,
      and conservation of myoglobin cDNA among fishes from two distinct families,
      suggest that a selective pressure operates to maintain myoglobin in the species
      that express the protein.

PMID- 9284560
TI  - Gonadotropin alpha-subunit glycoprotein from channel catfish (Ictalurus
      punctatus) and its expression during hormone-induced ovulation.
AB  - Complementary DNA (cDNA) encoding the channel catfish (Ictalurus punctatus)
      gonadotropin (GTH) alpha-subunit glycoprotein was cloned by polymerase chain
      reaction (PCR) from a plasmid library made from pituitary RNA. Complete cDNA
      cloning was achieved by carrying out two PCR reactions: one with an upstream
      sense primer plus the universal sequencing primer, located downstream of the
      poly(A) sequence of the cDNA in the plasmid vector, to amplify the downstream
      portion of the cDNA; the other with a downstream antisense primer plus the
      reverse-sequencing primer, located upstream of the very 5' end of the cDNA sense
      strand in the plasmid vector, to amplify the upstream portion of the cDNA. The
      two amplified fragments overlapping about 70 bp. Nucleotide sequence analysis
      revealed that the catfish GTH alpha-subunit was 658 bp encoding 116 amino acids
      and harboring a 5' nontranslated region (NTR) of 42 bp and a 3' NTR of 265 bp.
      The deduced amino acid sequence of the catfish GTH alpha-subunit is highly
      conserved with those from other cloned teleost GTH alpha-subunits. The GTH alpha
      subunit was highly expressed even before induction for ovulation in females
      during spawning season. Administration of carp pituitary extract (a spawning
      inducing reagent) induced only 1.4-fold higher expression of the GTH alpha
      subunit RNA, but included very rapid egg maturation and ovulation. This
      unexpected result indicated that the GTH alpha-subunit may not be the limiting
      factor for ovulation and spawning, which may be regulated by the change of
      proportional coupling of the GTH alpha-subunit with specific beta-subunit during
      hormone-induced ovulation.

PMID- 9284561
TI  - Amylase on Pecten maximus (Mollusca, bivalves): protein and cDNA
      characterization; quantification of the expression in the digestive gland.
AB  - The digestive enzyme alpha-amylase in Pecten maximus has been purified from the
      digestive gland, where it is present as two isoforms, In order to gain
      information on its structure and regulation, a digestive gland cDNA library,
      constructed in lambda phage Zap II (Stratagene, La Jolla, Calif., U.S.A.), was
      screened with a shrimp alpha-amylase cDNA probe. Only 0.02% of the clones were
      positive, and the longest clone, having a size of 1700 bp and identical to that
      of the mRNA, was fully sequenced. It contains the complete cDNA coding frame for
      one of the amylase isoforms of P. maximus. The deduced protein sequence is 508
      amino acids long, with a putative 18 amino acid, highly hydrophobic signal
      peptide and a mature enzyme of 489 residues. The molecular weight corresponds to
      54,500 Da and the calculated isoelectric point is 6.76. Locations of conserved
      sequences confirms the high level of similarity with the other members of the
      family.

PMID- 9284564
TI  - Ribosomal RNA gene dosage in marine bacteria.
AB  - Ribosomal RNA gene dosage was determined for 20 marine heterotrophic bacteria
      using short probes (< 600 bp) from the Escherichia coli 16S rRNA gene and
      Southern blot analysis. All Bacterial strains had between 4 and 10 copies of the
      16S rRNA genes in their genomes. This report presents important preliminary data
      for developing quantitative molecular methods to address population dynamics of
      marine based of 16S rRNA sequences.

PMID- 9284562
TI  - Alteration in plasmid DNA following natural transformation to populations of
      marine bacteria.
AB  - This article examines alterations in a broad-host-range plasmid (pQSR50) that
      were observed following transfer to indigenous marine bacteria by natural
      transformation. Plasmid DNA from the transformants had altered restriction
      profiles. However, with the exception of the EcoRI site from one transformant
      (BS10), fragments amplified by polymerase chain reaction (PCR) and encompassing
      the recognition sites were cleaved by the relevant endonucleases, providing the
      sites were present. Analysis with DpnI and MboI indicated differences in DNA
      methylation between pQSR50 and the transformants. The missing EcoRI site from
      BS10 and smaller EcoRI fragments observed in transformants indicated that
      rearrangements had also occurred. Evolution of novel plasmid molecules following
      gene transfer may be an important mechanism by which natural genetic diversity is
      generated.

PMID- 9284563
TI  - Recombinant expression of the antimicrobial peptide polyphemusin and its activity
      against the protozoan oyster pathogen Perkinsus marinus.
AB  - Polyphemusin is a broad-spectrum antimicrobial peptide isolated from hemocytes of
      the North American horseshoe crab Limulus polyphemus. To date the polyphemusin
      used for scientific analyses has been purified from the natural materials or
      obtained by chemical synthesis. We report here the recombinant expression in
      Escherichia coli, and subsequent purification, of a polyphemusin analogue
      (rLim1). To prevent toxicity of the antimicrobial peptide in the highly
      susceptible E. coli host, we used a carboxy-terminal fusion protein cloning
      strategy provided by a maltose-binding protein (MBP) gene fusion system (New
      England Biolabs). Antimicrobial activity of recombinant polyphemusin was similar
      to that seen with amidated native polyphemusin peptide. When rLim1 was tested for
      antibiotic activity against the apicomplexan protozoan oyster pathogen Perkinsus
      marinus, complete inhibition was observed at 12 micrograms/ml, and partial
      inhibition at 8 micrograms/ml.

PMID- 9284565
TI  - Molecular phylogenetics of bacterial endosymbionts and their vestimentiferan
      hosts.
AB  - Vestimentiferan tube worms from deep-sea hydrothermal vents and cold-water seeps
      rely entirely on sulfur-oxidizing bacterial endosymbionts for nutriment. We
      examined host-symbiont co-evolution by comparing phylogenetic trees from symbiont
      16S ribosomal DNA and host mitochondrial COI genes. The endosymbionts comprised
      two distinct clades, one associated with tube worms from basaltic vent habitats
      and the other associated with tube worms from sedimented seep-like environments.
      Within each symbiont clade, 16S rDNA sequences were nearly identical, suggesting
      that vent vestimentiferans share a single endosymbiont species that is distinct
      from the seep endosymbiont species. A third endosymbiont type, related to the
      seep species, was found in a tube worm collected from a whale carcass. Our
      results are consistent with a horizontal model of symbiont transmission.

PMID- 9284566
TI  - [Nutritional status of patients on chronic hemodialysis].
AB  - The objective was to determine the nutritional status (NS) in a population
      undergoing chronic hemodialysis (CHD), and correlate it with dialysis dose and
      morbimortality. A total of 55 patients, 27 men and 28 women, aged 47 +/- 15 and
      with a history of CHD of 54.6 +/- 47.6 months were evaluated. NS was classified
      into: adequate, mild malnutrition, moderate malnutrition and severe malnutrition.
      A score based on usual laboratory data (total iron-binding capacity [TIBC],
      albumin and cholesterol), clinical evaluation and anthropometric measurements
      (body mass index [BMI], mid brachial circumference, tricipital fold [TF], mid
      brachial muscle circumference [MBMC]), was used. In addition, a 7-days' intake
      auto-registration plan was conducted, and protein catabolic rate (PCR) was
      determined. Calorie intake was of 27 +/- 13 kcal/kg/day and protein intake was of
      1.2 +/- 0.5 g/kg/day. No correlation was found between the latter and PCR. 49.1%
      of patients had moderate to severe malnutrition, only 9 patients had an adequate
      NS. However anthropometric measurements showed that TF, MBMC and BMI were normal
      in 54.5%, 45%, and 72.7% of patients, respectively. No correlation was found
      between NS and age onset of CHD, sex, creatinine, dialysis dose (Kt/V x = 1.24 +/
      0.12), PCR and morbidity. A longer history of dialysis was associated with a
      worse NS (p < 0.01). In addition, NS significantly correlated with albumin (p <
      0.01) and mortality (p < 0.05). The estimated death risk was 9.45 times higher in
      patients with moderate and severe malnutrition.

PMID- 9284567
TI  - [Repeatability of insulin sensitivity estimation using the Minimal Model and
      comparison with a modified short low-dose insulin tolerance test].
AB  - Hyperinsulinemia and insulin-resistance are metabolic disturbances associated
      with obesity, essential hypertension, hypertriglyceridemia, glucose intolerance,
      overt non-insulin dependent diabetes mellitus, polymetabolic syndrome and
      atherosclerotic disease. The assessment of in vivo insulin sensitivity (SAI in
      vivo) changes achieved by life style modifications or drug interventions require
      a reproducible technique. To evaluate the day-to-day intra-individual
      repeatability of SAI-in vivo, we determined the variation in the SI index
      (calculated from the Minimal Model of Bergman modified by insulin or MMins) in 11
      subjects with a wide range of insulin-resistance. SI (first study) varied from
      0.82 to 8.48 x 10(-4) min-1/microU.mL (4.43 +/- 2.85 x 10(-4) min-1/microU.mL
      mean +/- SD) and highly correlated with SI (second study) (r = 0.89; p = 0.0002).
      The average interday coefficient of variation was 20.9 +/- 13.9% and was similar
      in subjects with low or high SI values. We also measured SAI in vivo by assessing
      the rate of serum glucose decline induced by human cristalline insulin 0.025 U/kg
      IV dose after a 12-14 hours fasting period (a modified Bonora's method or BBD) in
      11 subjects. No subject presented biochemical or symptomatic hypoglycemia. SAI in
      vivo values determined by BBD varied from 21 a 234 mumol/ml/min (134 +/- 64.8
      mumol/ml/min, mean +/- SD). We found a highly significant correlation between SI
      values obtained from MMins and SAI in vivo assessed by the BBD (r = 0.89, p =
      0.0002). Our results suggest that the Mmins is a fairly reproducible procedure
      and that a BBD is an acceptable option to quantify SAI in vivo, mainly when a
      fast-execution practice is necessary or cost restrictions are required.

PMID- 9284568
TI  - [Current situation of diabetic patients in hemodialysis in Buenos Aires].
AB  - The aim of this study was to evaluate the clinical and biochemical
      characteristics and the different types of treatment of diabetic patients in
      hemodialysis (HD) due to their end-stage renal disease (ESRD). The protocol was
      organized as a multicentric, case-control study and comprised twenty-nine HD
      centres from the city and province of Buenos Aires (PRODIHEM). The population
      sample included all diabetic patients in HD (n = 103) and the non diabetic
      patients hemodialyzed in the morning hours (n = 230) as controls. In this sample,
      the recorded prevalence for diabetes mellitus was 12%. Among diabetic patients,
      61% were non insulin dependent, 23% were insulin dependent and 16% were of the
      non insulin dependent type treated with insulin (Fig. 1). The results obtained in
      this study show that the current situation of diabetic patients in HD is far from
      being satisfactory: they require HD treatment at an early age; the disease is
      commonly associated with various comorbid factors not always appropriately
      treated; they show a fast deleterious progress towards ESRD, and they have a
      short halflife period in HD. The results also showed that there are no defined
      and common criteria for the treatment and control of these patients; thus, due to
      their poor clinical performance, only a small percentage reach a priority for a
      renal transplant.

PMID- 9284569
TI  - [Structure and ultrastructure of the endocrine pancreas in diabetic transgenic
      mice].
AB  - The aim of the present study was to confirm the structural changes and to
      establish the ultrastructural alterations that occur in the endocrine pancreas of
      mice with an induced insulin-dependent diabetes mellitus (IDDM) syndrome. For
      that purpose, we used transgenic mice (OVE 27) that overexpress a calmodulin gene
      in the beta cells of the endocrine pancreas. In these animals, the excess of
      calmodulin decreases the cytosolic calcium levels in beta cells, leading to
      morphological and functional alterations that produce a severe IDDM. Sections of
      pancreas (tail) from 4 male 5-week-old diabetic mice (glycemia: 376 +/- 2 mg/dl)
      and from 4 normal age-matched males (glycemia: 113 +/- 13 mg/dl) were processed.
      Light microscopic immunohistochemical observations confirmed a decrease in the
      number and size of pancreatic islets in transgenic mice, together with a
      disruption in their architecture, without an associated inflammatory response.
      The ultrastructural studies revealed diverse degrees of injury in the beta cells,
      such as the presence of membrane interdigitations and alterations in their
      organelles and secretory granules. These findings are in agreement with the
      quantitative and functional impairment of beta cells, coexisting with a normal
      appearance of non-beta cell populations within the pancreatic islets. Our results
      demonstrate the existence of ultrastructural changes in the pancreatic beta cells
      of the experimental model studied. Such changes, together with the
      immunohistochemical alterations previously described, contribute to explain the
      appearance of a diabetic syndrome in these animals.

PMID- 9284570
TI  - [Effect of insulin on contractile response and calcium binding in rat aorta].
AB  - Insulin affects physiological mechanisms involved in blood pressure regulation,
      and at the cellular level modifies endothelial and vascular smooth muscle
      functions underlying the changes in peripheral resistance. We describe the
      effects of preincubation with insulin (40 microU/ml for 1-2 hs) on the
      contractile reactivity of intact rat aortic rings and on 45Ca2+ uptake of EGTA
      hyperpermeabilized rat aortic segments. Preincubation with insulin did not affect
      either contractions induced by 1 microM of NA, or their relaxation induced by 10
      mM of caffeine. The contractile response to 1 microM of Ang-II (which in rat
      aorta is endothelium-independent) was stimulated by insulin preincubation
      resulting in increases of both maximal developed force and velocity of its
      spontaneous relaxation. The difference in 45Ca2+ uptake between insulin-treated
      and insulin-untreated aortic segments was greater at 5 minutes than it was at 30
      minutes. CONCLUSIONS: Insulin preincubation affects directly the mechanical
      response of Ang-II stimulated aortic smooth muscle; we suggest that the
      modification of SR function is one of the mechanisms involved in insulin
      regulation of cytosolic Ca2+.

PMID- 9284571
TI  - Varicocele in prepubertal boys. Evaluation of clinical Doppler and hormonal
      findings.
AB  - Hormonal, clinical and scrotal Doppler findings were assessed in 16 prepubertal
      patients having unilateral varicocele. As already described in pubertal patients,
      Doppler studies made it possible to detect patterns of prolonged, intermittent or
      permanent reflux. An LH-RH test and an hCG test measuring LH, FSH and
      testosterone (T) were performed in all cases. Patients with varicocele showed
      (median and range): LH B (mlU/ml): 0.40 (0.40-2.1); LH Mx.: 3.7 (1.1-15); FSH B
      (mlU/ml): 1.95 (0.40-4.5); FSH Mx.: 4.9 (3.1-10); T B (ng/ml): 0.2 (0.1-1.5); T
      Post.: 2.25 (0.82-11.5). The control group showed: LH B (mlU/ml): 0.40 (0.4
      0.85); LH Mx.: 2.15 (0.63-12) FSH B (mlU/ml): 1.45 (0.4-3); FSH Mx.: 4.25 (2.6
      5.9); T B (ng/ml): 0.1 (0.1-0.3); T Post.: 3.26 (1.0-5.6). No significant
      differences were found between the hormonal results of the different groups
      classified according to the scrotal findings. Basal LH and FSH in grade 3
      varicoceles were found to be significantly higher (p < 0.05) than those of the
      control group. Basal T, as well as the maximal response of both gonadotropins to
      LH-RH, and T response to hCG showed no significant differences with reference to
      the control group. Our findings provide indirect support to the notion that the
      gonadal damage would become detectable from puberty onwards.

PMID- 9284572
TI  - [Immunohistochemical characteristics of mammary carcinomas with estrogen-negative
      and progesterone-positive receptors].
AB  - In a series of 256 mammary carcinomas, 22 (8.5%) were positive for progesterone
      receptors (PR) and negative for estrogen receptors (ER). These cases seem to
      belong to a distinctive group with a biologic behavior not well understood. In
      order to contribute to a better understanding of such tumors, their association
      with different pathologic and immunohistochemical factors were compared with
      those of the rest of the tumors of the series. The results were that favorable
      factors such as smaller size, negative axillary lymph nodes and low histologic
      and nuclear grades were decreasingly associated with tumors that were ER+ PR+;
      ER+ PR-; ER- PR+; and ER- PR-. In relation to immunohistochemical features,
      tumors that were ER+ PR+; ER+ PR- and ER- PR+ behaved in a similar way, whereas
      ER- PR- tumors were different from the rest because fewer expressed bcl-2 (p =
      0.0000) and had a greater expression for p53 (p = 0.009) and MIB-1/Ki-67 (p =
      0.05). No significant differences were found between the four populations in
      recurrence rate or metastases, nor overall survival. In conclusion, these
      findings show that tumors that are ER- PR+ might have biological characteristics
      somewhere in between ER+ PR+ and ER- PR+.

PMID- 9284573
TI  - [Regional changes of ventricular motility in patients with positive serology for
      Chagas disease].
AB  - The aim of the present study was to carry out a quantitative assessment of the
      regional left ventricular wall motion and diastolic function of patients with
      Chagas disease in different clinical stages. Twenty patients with positive
      immunofluorescence tests for Chagas disease were studied. Eight patients were
      asymptomatic (class I), 9 patients had electrocardiographic abnormalities (class
      II) and 3 patients had heart failure (class III). The control group consisted of
      10 normal subjects. 2D echocardiographic images from parasternal and apical views
      were analysed quantitatively using a previously validated method for the
      assessment of the regional wall motion of the left ventricle. Diastolic flow
      velocities and times at mitral valve level were analysed using pulsed wave
      Doppler. Patients with Chagas disease showed marked wall motion abnormalities in
      the posterobasal segment compared with controls. These abnormalities were evident
      even in class I patients. The number of affected segments was higher in class II
      and class III. "A" wave velocity was greater in patients than in controls (0.67
      +/- 0.17 and 0.49 +/- 0.08 m/s, p = 0.01 respectively) but the pattern of
      diastolic flow velocity was non specific. In conclusion, regional left
      ventricular wall motion abnormalities are common in early stages of Chagas
      disease suggesting that myocardial activity of the disease is present even during
      the asymptomatic period.

PMID- 9284574
TI  - [Interaction of chagasic autoantibodies with the third extracellular domain of
      the human heart muscarinic receptor. Functional and pathological implications].
AB  - Herein we demonstrate by ELISA and immunoblotting the presence in the sera of
      chagasic patients of circulating autoantibodies against the third extracellular
      domain of human muscarinic acetylcholine receptors by using a synthetic peptide
      corresponding to the sequence 169-192 of the receptor. Immunoaffinity purified
      antipeptide antibodies displayed cardiac muscarinic activity as decreased
      contractility and cAMP production and increased cGMP levels. These effects were
      specifically blocked by the synthetic peptide and by atropine. A strong
      association between the existence of circulating autoantibodies and the presence
      of dysautonomia was shown, making these autoantibodies an appropriate marker of
      heart autonomic dysfunction.

PMID- 9284575
TI  - [Evaluation of cytokine production in leprosy patients].
AB  - The aim of the present study was to evaluate the cytokine production by
      peripheral blood mononuclear cells (PBMC) of leprosy patients when the cells were
      stimulated in culture by ConA, PPD or M.leprae. We measured IL-2, IL-4, IFN-gamma
      and IL-6 in cell-free supernatants by enzyme linked immunoassays. Our results do
      not suggest a clear association of a clinical form of leprosy with either Th1 or
      Th2 cytokine secretion profile in PBMC of leprosy patients.

PMID- 9284576
TI  - Hantavirus pulmonary syndrome in Argentina. Possibility of person to person
      transmission.
AB  - In March 1995 the first case of a familiar outbreak of Hantavirus pulmonary
      syndrome (HPS) was notified in El Bolson, in the South of Argentina. Until
      December 15, 1996, a total of 77 cases of HPS had been notified with 48%
      mortality, distributed in three geographical areas of the country, South, North
      and Center. During 1996, of the 19 cases from El Bolson, three were local
      physicians, one of whom -during the prodrome of her illness- travelled to Buenos
      Aires to be attended. In the hospital, two of the physicians who assisted her,
      developed HPS 27 and 28 days after the first contact. These data suggest for the
      first time the possibility of interhuman transmission of the Hantavirus
      responsible for the pulmonary syndrome.

PMID- 9284577
TI  - [Primary CNS lymphoma. Infratentorial localization and prolonged survival].
AB  - A case of a 35-year-old woman presenting infratentorial CNS lymphoma is reported.
      In 1990 she complained of diplopia, blurred vision and left horizontal nistagmus.
      An MRI disclosed a lesion in the medulla, pons, and cerebellar vermis and
      peduncles. Although no treatment was administered, a later RMI showed less
      extension of the tumor. One year after clinical diagnosis, she received
      corticosteroids; during the second year a stereotaxic biopsy of the cerebellar
      lesion was done showing a diffuse B cell non-Hodgkin's lymphoma. A whole brain
      irradiation was given (50 Gy). She did well for five years, and remains alive (79
      months).

PMID- 9284579
TI  - [Participation of fragile sites in cancer].
AB  - Structural and numerical chromosomal abnormalities are frequent findings in
      neoplastic cells. The origin of structural rearrangements is probably due to the
      existence of specific labile areas on human chromosomes. These areas, named
      fragile sites (FS), are prone to chromosomal breakage and rearrangements, playing
      an important role in the first steps of carcinogenesis. The classification of FS,
      the mechanisms involved in FS induction and their biological significance,
      specially their relationship with cancer development, are discussed.

PMID- 9284578
TI  - [Lymphoma, hepatosplenomegaly, hemiparesis].

PMID- 9284580
TI  - [Nobel Prize in Physiology and Medicine 1996: Rolf Zingernagel and Peter Doherty.
      Immune recognition: self, non-self and modified self].

PMID- 9284581
TI  - [A century and a half of the first surgical anesthesia].

PMID- 9284582
TI  - [Microscopy and flow cytometry: increased CD4 expression in monocytes of HIV
      infected patients].

PMID- 9284584
TI  - [Homeopathy].

PMID- 9284583
TI  - [Gas exchange changes after heart surgery].

PMID- 9284585
TI  - [The oral provocation test by an alternative drug in patients with
      hypersensitivity to acetylsalicylic acid/non-steroidal anti-inflammatory agents].

PMID- 9284586
TI  - Epidemiology of HAV infection in Piedmont, Italy.

PMID- 9284587
TI  - Central venous line related bacteremia during total parenteral nutrition and/or
      chemotherapy infusions in children.

PMID- 9284589
TI  - Research on the leakage of electromagnetic radiation to the exterior of microwave
      ovens after domestic use.

PMID- 9284588
TI  - The "Di.S.Co." project: a community-based comprehensive control project of
      chronic diseases. Time change in intervention strategy. The "Di.S.Co." Research
      Group.

PMID- 9284590
TI  - Resources allocation to OPD services at public and private dispensaries in Iringa
      District, Tanzania.

PMID- 9284591
TI  - Eleven-year tracking of established cardiovascular risk factors in Italian school
      aged children.

PMID- 9284592
TI  - Knowledge, attitudes and practice of paediatricians towards measles and pertussis
      vaccinations in a large Italian region.

PMID- 9284593
TI  - Angioedema due to angiotensin-converting enzyme inhibition: an association
      frequently unrecognized.
AB  - Angioedema as a side effect of treatment with angiotensin-converting enzyme
      inhibitors is often under-recognized. We analyzed the subjects seen in our out
      patient clinic for angioedema. Over the past 3 years, we have found a cause
      effect relationship between angiotensin-converting enzyme inhibitor treatment and
      angioedema in 14 of the 334 subjects presenting with this condition.

PMID- 9284594
TI  - Pathogenesis and therapy of Behcet's disease.
AB  - Behcet's disease is a relapsing-remitting systemic vasculitis characterized by
      oral and genital ulcers, uveitis and thrombophlebitis which can involve many
      organs. Although its pathogenesis is not fully understood, a possible
      pathogenetic model can be proposed on the basis of recent studies. Genetic
      factors, in particular, have been investigated and the role of the genes encoding
      tumor necrosis factor, transporter in antigen processing proteins and MIC (MHC
      class I chain related) has been emphasized. In addition, a possible polarization
      of T lymphocytes towards the Th1 phenotype in Behcet's disease has been suggested
      by recent observations in experimental uveoretinitis and by preliminary data in
      humans. Neutrophils may also play a role in the pathogenesis of this disease, as
      they are attracted by macrophage-released cytokines at the site of the lesions,
      and thus contribute to tissue damage and self-maintenance of inflammation. New
      strategies for the treatment of Behcet's disease are being devised. In
      particular, immunosuppressive drugs used in association or in sequence may be
      administered to patients with particular clinical features or very severe
      disease.

PMID- 9284595
TI  - Noninvasive assessment of posterior cerebral artery stenosis inducing hemiplegia.
AB  - Posterior cerebral artery infarction usually causes hemianopsia and,
      occasionally, symptoms referred to infarction in the territory of the middle
      cerebral artery. We describe a case of cerebral infarction of the posterior
      cerebral artery territory that mimicked middle cerebral artery occlusion. A
      patient with infarction of the right surface and deep territories of the
      posterior cerebral artery presented with left hemiplegia and left homonymous
      hemianopsia. Brain computed tomography and magnetic resonance investigation
      disclosed a hypodense lesion in the occipital right lobe and the medial and
      inferior part of the right temporal lobe. Transcranial Doppler studies disclosed
      an abnormally increased blood flow velocity in the proximal posterior cerebral
      artery and a sharp reduction in distal flow velocity. This case underscores the
      utility of noninvasive techniques to diagnose posterior artery stenosis: they
      were not only more economical than angiography but also spared the patient
      discomfort and risk.

PMID- 9284596
TI  - Systemic infection by JC virus in non-HIV induced immunodeficiency without
      progressive multifocal leukoencephalopathy.
AB  - Reactivation of latent JC virus in immunodeficient subjects can lead to a
      demyelinating disease following lytic oligodendrocyte infection. It is known as
      idiopathic CD4+ lymphocytopenia and rarely occurs in immunosuppressed patients
      who are not infected by HIV. We describe a case of persistent idiopathic CD4+
      lymphocytopenia in an HIV-negative 65-year-old woman. At autopsy, polymerase
      chain reaction analysis evidenced JC virus DNA in kidney, brain and liver
      although there were no signs of progressive multifocal leukoencephalopathy or
      evidence of oligodendrocyte infection. While her disease was not HIV-induced, it
      closely resembled AIDS in terms of the nature of the immune derangement and the
      clinical picture. The case also evidences the reactivation of JC virus infection
      in non-HIV-related immunosuppression in cerebral and/or extracerebral sites:
      liver infection seems to be particularly relevant since it has not yet been
      recognized as a common target of JC virus infection or a source of virus
      spreading. The absence of any sign of progressive multifocal leukoencephalopathy
      was remarkable: histological examination failed to disclose demyelination or
      other progressive multifocal leukoencephalopathy changes, and the search for JC
      virus DNA with in situ methods also gave negative results. The lack of lytic
      brain infection in this case would seem to support the hypothesis that the
      expression of progressive multifocal leukoencephalopathy is directly dependent on
      the presence of HIV infection.

PMID- 9284598
TI  - Leukoaraiosis and lacunar infarcts in ischemic stroke: role of age and vascular
      risk factors.
AB  - To assess the role that age and some vascular risk factors play in the
      pathogenesis of leukoaraiosis and lacunar infarcts in patients with ischemic
      stroke, we examined 71 consecutive patients who had undergone magnetic resonance
      imaging because of clinical suspicion of stroke. We collected data regarding
      hypertension, diabetes mellitus, cardiac diseases, hypercholesterolemia, and
      hematocrit, and compared patients with lacunar infarcts to those with cortical or
      subcortical nonlacunar lesions. Patients were then assigned to one of two age
      groups, Group A (< or = 66 years), or Group B (> 66 years). We found a
      significant correlation between the presence and severity of leukoaraiosis and
      the presence of lacunar infarcts in both groups. In Group A, however, lacunar
      infarcts were correlated to hematocrit, while in Group B they were correlated to
      a trend to hypertension. Leukoaraiosis was correlated to hypertension only in
      Group A. Although we noted a strong correlation between leukoaraiosis and lacunar
      infarcts suggesting a common small-vessel disease, our data indicate that
      different pathogenetic mechanisms are involved. We suggest that patients be
      grouped according to age in future studies on the role that risk factors play in
      the pathogenesis of leukoaraiosis and lacunar infarcts.

PMID- 9284597
TI  - Rationale for the use of a low molecular weight heparin during hemodialysis with
      polysulphone membrane in uremic patients.
AB  - We carried out an open, randomized, cross-over study to test the rationale for
      use of a low molecular weight heparin during hemodialysis with polysulphone
      membranes. Ten uremic patients (6 men, 4 women, mean age 50 +/- 11 years, range
      31-70) in chronic hemodialysis underwent paired filtration dialysis with either
      low molecular weight heparin or unfractionated heparin, then crossed over to the
      other anticoagulant treatment. We measured the following: anti-factor Xa and anti
      factor IIa activity in patients' plasma and in the ultrafiltrate, activated
      partial thromboplastin time and bleeding time before, during and after
      hemodialysis. Some low molecular weight fractions of heparin were lost in the
      ultrafiltrate during hemodialysis, while higher molecular weight fractions were
      retained. The activated partial thromboplastin time during dialysis and the
      bleeding time after dialysis were more prolonged with unfractionated heparin than
      with the low molecular weight heparin (p < 0.01 and p < 0.05 respectively). Our
      data indicate that the use of a low molecular weight heparin determines a less
      pronounced prolongation of the activated partial thromboplastin time during
      dialysis and prevents a post-dialytic increase in bleeding time.

PMID- 9284599
TI  - Adverse drugs reactions associated with glaucoma medications.
AB  - We undertook a non-concurrent prospective study of 191 Puerto Rican patients from
      August 1993 to April 1994. All patients had open angle glaucoma (OAG) (age ranged
      from 50 to 80 yrs; mean = 65 yrs). Patient's symptomatology associated to side
      effects of their glaucoma medicadons was reviewed. Incidence percent of ocular
      and/or systemic side effects per medication were: levobunolol 45.0%; betaxolol
      42.0%; timolol 27.3%; pilocarpine 100%; dipivefrin 14.0%; and acetazolamide 250
      mg 64.1%. Incidence percent of ocular and/or systemic side effects of topical
      beta-blockers used with concomittant medications were determined. Ocular side
      effects were more frequent in patients using levobunolol 44.2% than in those
      patients using betaxolol 42.0%, 8.5% of patients using levobunolol did report
      systemic side effects. No systemic side effects were reported by patients using
      betaxolol. Ocular side effects in patients using pilocarpine were frequent
      (100%); whereas the frequency of systemic side effects was low (6.1%). Systemic
      side effects were common in patients using carbonic anhydrase inhibitors. These
      results suggest that non-selective and cardio-selective topical Beta-blockers,
      differ in their ocular or systemic side effects.

PMID- 9284600
TI  - Botulinum toxin A for the treatment of achalasia.
AB  - Pneumatic balloon dilatation of the esophagus is one of the current recommended
      treatment for achalasia. This procedure is associated with risks such as
      esophageal rupture. Surgery and percutaneous gastrostomy tube placement has been
      performed in severely affected individuals. The Botulinum Toxin A (BoTxA) is
      widely used to treat neuromuscular conditions in which spasticity is of concern.
      We present four cases in which BoTxA was used as an alternative of treatment and
      in which less invasive modalities were unsuccessful. The patients received a
      total of 80 units of BoTxA, applied to the submucosa in doses of 20 units in each
      predetermined quadrants to the lower esophageal sphincter. All patients
      demonstrated improvement of their symptoms without side effects in this study.

PMID- 9284601
TI  - Incidence of abnormal right ventricular filling patterns in adults: a
      retrospective echocardiographic study.

PMID- 9284604
TI  - What is your diagnosis? Atrial flutter with 1:1 conduction and RBBB aberrancy.

PMID- 9284602
TI  - Biliary complications and management of cystic fibrosis.

PMID- 9284603
TI  - Echocardiographic appearance of an iatrogenic mediastinal hematoma.

PMID- 9284605
TI  - Role of Internet in medicine.
AB  - Internet, the largest network of connected computers, is becoming the ultimate
      frontier to access information for health providers. This review focus on how
      developments of this communication technology have become a useful educational
      resource in medicine, and describes modest ideas in computer network use.
      Internet basic resources are electronic mailing (E-mail), discussion groups, file
      transfer, and browsing the World Wide Web (WWW). E-mail brings physicians with
      common interest together. Surgeons employ it as a communicating tool. Legal and
      social responsibility is bounded with its use. Discussion groups permits debate
      including clinical cases, operations, techniques research, career opportunities,
      and meetings. File transfer provides the opportunity of retrieving archives from
      public libraries. The WWW is the most resourceful tool due to its friendly
      interface and ease of navigation. The average physician needs to know almost
      nothing on how computers work or where they came from to navigate through this
      pandemonium of information. Click and play with today graphical applications
      encourage the computer illiterate to connect. Establishing the connections
      envelops the need of hardware, software and a service provider. Future
      development consists of online journals with new ideas in peer-review and
      authentication, telemedicine progression, international chatting, and
      centralization of cyber space information into database or keyword search
      engines.

PMID- 9284606
TI  - Number of AIDS deaths decline in US.

PMID- 9284608
TI  - Protease-inhibitors linked with hyperglycemia in HIV-infected patients.

PMID- 9284607
TI  - Possible transmission of HIV via mucous membrane?

PMID- 9284609
TI  - Mislabeling of drug for Kaposi's sarcoma rectified.

PMID- 9284610
TI  - A relationship exists between sexually transmitted disease (STD) and the human
      immunodeficiency syndrome (HIV)

PMID- 9284611
TI  - A challenge to the profession: initiate evidence-based osteopathic medicine now.

PMID- 9284612
TI  - Somatic dysfunction increase during caffeine withdrawal.
AB  - The authors studied the effects of caffeine withdrawal on 14 subjects at baseline
      and during a 4-day period of abstinence from caffeine. They studied the results
      from quantitative electroencephalograms performed on these subjects and gauged
      any changes that may have been evoked during this withdrawal period. The
      participants were also evaluated for the occurrence of somatic dysfunctions.
      Examinations for the presence of somatic dysfunctions were performed on the
      participants before caffeine cessation and on Days 1, 2 and 4 of abstinence.
      Results showed that the number of somatic dysfunctions increased significantly
      during the process of caffeine withdrawal.

PMID- 9284613
TI  - Skin-to-skin parental contact with fragile preterm infants.
AB  - Skin-to-skin contact has been implemented recently to facilitate maternal-infant
      bonding of preterm infants. The technique allows the removal of fragile preterm
      infants from an incubator to the bare chest of a parent or caretaker. When
      specific guidelines are followed, thermal stability can be maintained, parent
      infant bonding can be facilitated, and parental satisfaction can be enhanced. We
      illustrate a case in which a preterm infant has skin-to-skin contact while being
      monitored for physiologic parameters, including heart and respiratory rate,
      oxyhemoglobin saturation, and nasal airflow. Improvements in breathing patterns
      in this infant during skin-to-skin care and maintenance of a normal temperature
      suggest that this technique may not only be safe and psychologically beneficial,
      but it may also promote physiologic improvement.

PMID- 9284614
TI  - Excision of urethral diverticulum calculi in a pregnant patient on an outpatient
      basis.
AB  - Although the incidence of urethral diverticula in women of reproductive age
      ranges from 0.6% to 6%, urethral diverticulum calculi are rarely reported. This
      report describes excision and outpatient management of urethral diverticulum
      calculi in a symptomatic pregnant patient. The etiology, diagnosis, and
      recommended therapy of urethral diverticulum calculi are discussed. Historically,
      surgical therapy has been considered appropriate; however, recent technologic
      advancements--including ultrasound and lithotripsy--may change this widely
      accepted method of treatment.

PMID- 9284615
TI  - An osteopathic prescription for medical education reform: Part 2. Specialty mix
      and community integration.
AB  - Calls for medical education reform focus on four major criticisms directed at
      curricular content and context, infrastructure fragmentation, specialty mix, and
      the lack of integration with community and public health. In the previous article
      in this two-part series, authors from the osteopathic medical education community
      focused on uniquely osteopathic reforms for the curriculum and the fragmented
      educational system. That article documented the leadership position of
      osteopathic medical education in implementing reforms with respect to these two
      criticisms. The authors of this second article tackle the osteopathic
      contributions to workforce issues related to the generalist-to-specialist
      imbalance, the opportunities to move from a community-based profession to a
      profession accountable for community health, and the potential for technologic
      advances to aid in reform in all four areas under consideration in both articles.
      They conclude that the osteopathic medical profession can lead medical education
      reform in the United States with visionary leadership in place.

PMID- 9284616
TI  - [Objective visual function tests for retinal pathophysiology].

PMID- 9284617
TI  - [Fundus hypothermia inhibits retinal damage induced by visible blue light].
AB  - We evaluated the role of fundus hypothermia in modifying photic retinopathy. The
      fundus was cooled with a copper plate inserted behind the eyeball. The anterior
      end of the plate was chilled with dry ice. Retinal temperature was thus reduced
      to 30 and 33 degrees C. This cooling manipulation had no effect on body
      temperature, retinochoroidal architecture, or choroidal circulation. The fundus
      was then exposed to visible blue light at an irradiance of 8 mW/cm2 for one hour.
      Retinal damage developed in 9 out of 10 eyes after the exposure alone, and in 3
      out of 10 eyes when retinal temperature was reduced to 30 degrees C. The
      incidence of light damage with the cooling manipulation was decreased
      significantly when compared to that of controls (p < 0.05). Contrary to this, 5
      out of 5 retinas treated with hypothermia at 33 degrees C showed damage and there
      was no significant difference in the incidence from that of controls. This
      finding indicates that local hypothermia at 30 degrees C protects the retina from
      light damage and that a subtle temperature milieu plays a role in producing
      retinal damage.

PMID- 9284618
TI  - [Protective effect of nitric oxide on ischemic retina].
AB  - Nitric oxide (NO) is a free radical and was regarded as noxious to life. But
      recent studies show that NO is an important substance for transcellular signal
      transduction. It also seems to act as a neurotransmitter in the nervous system.
      In ischemic nerve tissue a release of glutamate is one of the critical factors
      that increase neuronal death, and some experiments suggest that NO may be
      involved in this process. Here we provide evidence that NO provides
      neuroprotection in ischemic retinas in vivo. Albino rabbits' eyes were subjected
      to 60 minutes of ischemia by raising intraocular pressure. Before ischemia the
      eyes were treated intravitreously with the NO-precursor L-arginine, the NO
      synthase-inhibitor nitro-L-arginine methyl ester hydrochloride (L-NAME), the NO
      donor sodium nitroprusside (SNP), or solvent only. The amplitude of the b-wave
      was measured and the recovery ratio of the b-wave was analyzed hourly after
      reperfusion. The recovery ratio of b-wave in the eyes with L-arginine and with
      SNP increased more rapidly than in the controls, while the recovery ratio in the
      eyes with L-NAME increased in a way similar to that of the controls. These
      results suggest that NO plays a neuroprotective role in ischemic retina. It may
      be involved with S-nitrosylation of some proteins, including one of the glutamate
      receptors, the N-methyl-D-aspertate (NMDA) receptor.

PMID- 9284619
TI  - [Visual acuity measured by pattern visual evoked potential].
AB  - We investigated the appropriateness of a method for the assessment of visual
      acuity using pattern visual evoked potentials (PVEP) in which retinal X-ganglion
      cells are predominantly stimulated. Eighteen normal eyes (average 22.2 years old)
      with normal acuity of 1.0 were examined. The stimulus consisted of white and
      black checkerboards (39', 26', 15' and 9') with a visual angle of eight degrees
      and a contrast level of 15%. The pattern reversal frequency was 0.7 Hz. This
      resulted in 100 averaged PVEP per session. We judged visual acuity from responses
      of the P100 component. Visual acuity was judged to be 0.1, so that there was
      response to the 39' checkerboard stimulus pattern, but not to the 26' pattern.
      Consequently, the accuracy for visual acuity was 76.9% for 0.1, 71.4% for 0.2,
      70.0% for 0.5 and 58.3% for 1.0. This method, which uses a stimulus pattern with
      a small visual angle, low contrast, and low pattern reversal frequency, is useful
      for subjective measurement of the visual acuity of infants or handicapped
      children whom it is difficult to measure by the conventional objective method of
      measuring visual acuity with Landolt's rings.

PMID- 9284620
TI  - [Sensitivity loss of short wavelength sensitive cones in myopic eyes by blue-on
      yellow perimetry].
AB  - A decrease of the short wavelength sensitive cone (S-cone) sensitivity has been
      reported in myopic eyes in addition to glaucoma and retinal diseases such as
      retinal detachment and diabetic retinopathy. In order to investigate early
      changes of visual function in myopic eyes, blue-on-yellow perimetry (B on Y)
      which could detect S-cone sensitivity and white-on-white perimetry (W on W) were
      measured with a computed perimeter program. Young subjects with good visual
      acuity, normal color vision, and normal intraocular pressure were selected. They
      had no other ophthalmoscopic abnormalities except for tigroid fundus. Mean
      deviations of W on W were reduced in mild and high myopic groups. In both tests,
      the sensitivities decreased as the refractive errors increased in all the tested
      areas (p < 0.0001). The sensitivity in B on Y decreased more remarkably than in W
      on W with an increase of refractive error (p < 0.05). We concluded that B on Y
      perimetry was significantly sensitive to identify early changes of visual
      function in myopic eyes.

PMID- 9284621
TI  - [Proliferative vitreoretinopathy treated with daunorubicin].
AB  - Nine eyes with severe proliferative vitreoretinopathy underwent vitrectomy and
      infusion of Daunorubicin to prevent reproliferation. In 5 eyes (56%) the retina
      was reattached. In 4 eyes redetachment occurred because of reproliferation or
      incomplete sealing of the break. After a second vitrectomy, complete reattachment
      of the retina was obtained eventually in all eyes including one eye with silicone
      oil tamponade. As postoperative complications, conjunctival dehiscience occurred
      in 3 eyes. In two of the 3 eyes scleral buckling occurred, and orbital cellulitis
      occurred in one eye. Daunorubicin seemed to be effective to suppress
      reproliferation, but care should be taken to avoid postoperative complications.

PMID- 9284622
TI  - [Pterygium and mast cells--mast cell number, phenotype, and localization of stem
      cell factor].
AB  - We examined the number and phenotype of mast cells, and the localization of stem
      cell factor (SCF) as a growth factor of mast cells in the excised tissue of 38
      cases of pterygium. In histopathology with toluidine blue stain and
      immunohistochemistry with a monoclonal antibody to tryptase, the mean mast cell
      count in pterygium specimens was twice as high as in normal conjunctiva. In
      pterygium specimens more than 94% of tryptase-positive mast cells were found to
      express chymase and c-kit. There was no phenotypic difference between mast cells
      in pterygium and normal conjunctiva. In all immunohistochemical specimens in
      which we could examine the head of the pterygium, SCF was expressed in
      subepithelial fibroblasts at the central edge of pterygium. The results suggest
      that overexpression of SCF was accompanied with the augmentation of mast cells in
      the pterygium.

PMID- 9284623
TI  - [Retinitis pigmentosa and color vision deficiency in Kamigoto island, Nagasaki
      Prefecture].
AB  - I studied two genetic diseases, retinitis pigmentosa (RP) and color vision
      anomaly, in Kamigoto, one of the off-shore islands in Nagasaki Prefecture. The
      Prevalance of RP patients in this island was estimated to be one in 473 persons.
      Among the RP patients observed, familial cases whose disorders are transmitted
      through successive generations comprised 25.7%. Although it seems that the
      inheritance mode of RP in these familial cases is autosomal dominant, an
      autosomal recessive fashion showing quasi-dominance cannot be ruled out, because
      inbreeding frequently occurs on this island. There were at least two types of RP,
      one with late onset (40 years of age or later) and the other with early onset,
      and patients with the latter RP tended to have a poor prognosis. Only a few RP
      patients had posterior subcapsular cataract, and none had pseudexfoliation in
      spite of advanced age. Color vision anomalies were found in 3.86% of high-school
      boys and in 0.41% of girls in this island, and they included protanopia (4.2%),
      protanomaly (10.4%), deuteranopia (37.5%), and deuteranomaly (47.9%). The
      prevalence in boys was comparable to that in the general Japanese population, but
      the prevalence in girls was higher in Kamigoto than in other districts. It is
      most likely that the unique findings regarding the two disorders reflect
      geographical and/or social features in Kamigoto island.

PMID- 9284624
TI  - [Immunohistochemical distribution of keratin in malignant tumors of eyelids].
AB  - The type and distribution of keratins (K) in malignant tumors of eyelids were
      examined immunohistochemically to understand the pathomechanism of intercellular
      interactions. All of the tumor cells in the basal cell carcinoma were positive
      for K14, which is specific for basal cells, whereas all of them were negative for
      K10, which is specific for suprabasal layers in stratified squamous epithelia.
      These findings suggest that basal cell carcinoma may consist of uniform, basal
      cell-like tumor cells. On the other hand, the squamous cell carcinoma and
      sebaceous carcinoma, which were positive for either K14 or K10 to varying extent,
      may consist of various tumor cells with different types and degrees of
      differentiation. In these tumors, K14 was frequently detected throughout the
      border cells of the tumor mass. Apoptotic bodies were detected at the region
      where this continuous distribution of K14 was interrupted. These findings may
      help to clarify the pathomechanism of the interactions between the tumor cells
      and stromal cells.

PMID- 9284625
TI  - [Analysis of choroidal blood flow by laser speckle flowgraphy].
AB  - We applied real-time laser speckle flowgraphy (RLSFG) to quantitate the choroidal
      circulation. RLSFG was developed utilizing the laser speckle phenomenon. A diode
      laser, 830 nm in wavelength, serves as the light source. The quantitative index
      of blood flow velocity is represented as normalized blur (NB), or square blur
      rate (SBR). This method was applied to the posterior fundus of monkey and human
      eyes. While one measurement covers a fundus area of 1 mm x 1 mm, it is possible
      to measure a wider fundus area by montage. The wide color maps showed the
      architecture of choroidal vessels. It was possible to measure the choroidal blood
      flow in areas free of major retinal vessels. Application of the method to 3 eyes
      of retinal artery occlusion and 4 eyes of geographic choroiditis showed that the
      obtained SBR values in normal fundus is derived 25% from the retinal and 75% from
      the choroidal circulation. The findings show the potential value of RLSFG in
      quantitating the choroidal blood flow in situ.

PMID- 9284626
TI  - [Vitreous surgery for macular hole followed membrane peeling].
AB  - We performed vitreous surgery for macular holes following membrane peeling. The
      cases were five eyes of five females aged 42 to 67 years at the time of membrane
      peeling, out of 441 eyes of 414 patients who underwent membrane peeling. One eye
      had secondary epiretinal membrane combined with ocular sarcoidosis, two eyes had
      idiopathic epiretinal membrane, and two eyes had idiopathic vitreoretinal
      traction syndrome. The presumed interval from membrane peeling to macular hole
      formation was 5 to 90 months (average 14 months). For treatment of the macular
      holes, membrane peeling and SF6 gas tamponade were performed. In four eyes of the
      five eyes, the macular hole was closed. In the remaining eye, removal of the
      retinal pigment epithelium from the base of macular hole and application of
      fibrin glue were used in addition to SF6 gas tamponade, but the macular hole was
      not closed. The follow-up term was 10-24 months (average 17.6 months).
      Geometrical mean visual acuity was 0.34 before membrane peeling, 0.94 at maximum
      after membrane peeling, 0.19 after macular hole formation, 0.51 at maximum after
      macular hole surgery, and 0.44 at the final visit.

PMID- 9284627
TI  - [A case of congenital retinoschisis with unexpected appearance and spontaneous
      regression].
AB  - A case of congenital retinoschisis, with both unexpected appearance and
      spontaneous regression, is reported. The patient, a 22-year-old man, had been
      diagnosed with congenital retinoschisis when he was 11 years old. The ocular
      fundus showed bilateral foveal retinoschisis and peripheral retinoschisis in the
      right eye. Early in November 1991, he visited our hospital and complained of a
      visual field defect in the left eye. The ocular fundus of the left eye showed
      high ballooning retinoschisis. However, two weeks later, the ballooning
      retinoschisis had completely disappeared. Appearance and regression of peripheral
      retinoschisis of congenital retinoschis in an adult is a very rare occurrence.

PMID- 9284630
TI  - Integrated management of childhood illness.

PMID- 9284631
TI  - Combined effect of Web 2086 (Paf antagonist) and ketoprofen (Nsaid) on Paf
      induced ex vivo platelet aggregation in bovine.
AB  - The effect of the specific PAF-antagonist WEB 2086, a thieno-triazolo-diazepine,
      and ketoprofen, a NSAID, was investigated on PAF-induced bovine platelet
      aggregation measured ex vivo in platelet-rich plasma (PRP). WEB 2086 was infused
      intravenously over 1 min followed immediately by ketoprofen administration over 1
      s (both drugs = 3 mg/kg), in a group of six healthy male Friesian calves.
      Depending on the PAF concentration, a reversible (10(-8)-10(-9) mol/l) and
      irreversible (10(-5)-10(-7) mol/l) platelet aggregation was observed. The
      reversible aggregation was completely blocked by pretreatment of the animal with
      WEB 2086 and ketoprofen. The inhibitory effects observed during the irreversible
      aggregation were 47.22%, 54.00% and 88.00% at 10(-5), 10(-6) and 10(-7) mol/l
      PAF, respectively. Moreover, the aggregation obtained in these condition became
      reversible. Maximal inhibitory effect of WEB 2086 and ketoprofen on PAF-induced
      platelet aggregation in calves was observed within 30 min after administration of
      both drugs. This inhibition persisted even after 24 h and was significantly
      different from control with P < 0.05. The combined effect of both drugs exceeded
      the sum of the individual effects (synergism). It was concluded that WEB 2086 and
      ketoprofen very effectively blocked PAF-induced bovine platelet aggregation in
      platelet-rich plasma. The study also suggested a synergism between both
      substances.

PMID- 9284632
TI  - Transport of propionate across the distal colonic epithelium of guinea pig in the
      presence and absence of bicarbonate and of chloride.
AB  - Short-chain fatty acids (SCFA) are rapidly absorbed in the large intestine.
      However, the mechanisms involved have not been fully delineated. Findings
      indicate that absorption of SCFA occurs in the undissociated form as well as by
      an anion exchange, whereby marked species and segmental differences are present.
      The guinea pig distal colon has certain peculiarities. Unidirectional fluxes of
      propionate across guinea pig distal colon were studied under short-circuit
      current conditions in Ussing chambers. Removal of bicarbonate caused reduction of
      mucosal-to-serosal fluxes by 30%, serosal-to-mucosal fluxes were little affected.
      In chloride-free solution unidirectional fluxes were also reduced. However, in
      the presence of transepithelial chloride-gradients with the Cl(-)-free solution
      only at the luminal side, no such effects were seen. Findings support the
      presence of SCFA(-)-HCO3- exchange in guinea pig distal colon. Chloride seems not
      of major importance for SCFA transport.

PMID- 9284633
TI  - Pulmonary function values in Friesian and double-muscled calves during acute
      poikilocapnic hypoxia.
AB  - The effects of an acute non-isocapnic hypoxia on ventilation and pulmonary
      mechanics were investigated in 6 healthy unsedated Holstein-Friesian (HF) calves
      and in 7 double-muscled calves of the Belgian White and Blue (BWB) breed known to
      develop more severe hypoxemia during exercise and respiratory diseases. Data were
      collected at 1 min intervals throughout the following protocol: breathing air
      (FIO2 = 21%), then breathing hypoxic gas mixture (FIO2 = 10%) for 5 min, and,
      finally, breathing air again for 5 min of recovery. Arterial blood was sampled at
      rest and at the 4th min of hypoxia for blood gas analysis. In HF and BWB calves,
      hypoxia induced a significant increase in tidal and minute volume, but did not
      change respiratory rate, dynamic lung compliance and total pulmonary resistance.
      However, with regard to their ventilation during normoxia at rest, BWB calves
      showed a comparatively greater rise in ventilation than HF calves during the
      first 4 min of hypoxia. On the contrary, by the 5th minute of hypoxia,
      ventilation of BWB calves declined to the normoxic level while HF calves largely
      sustained hyperventilation. This hypoxic ventilatory depression in BWB calves
      could be explained by the proportionately greater initial increase in
      ventilation. It was concluded that BWB calves supported this hypoxic challenge
      less easily than HF calves.

PMID- 9284634
TI  - Plasma and liver alpha-tocopherol in dairy cows with left abomasal displacement
      and fatty liver.
AB  - Thirty dairy cows with left abomasal displacement (LAD) and 14 healthy control
      cows were studied to assess the status of the natural antioxidant vitamin E,
      lipid peroxidation in the liver (malondialdehyde-formation) and its relationship
      to hepatic lipidosis. Blood concentrations of alpha-tocopherol, aminotransferase,
      glutamin dehydrogenase, free fatty acids, beta-hydroxybutyrate and glucose were
      determined. alpha-tocopherol, tryglyceride, glycogen and malondialdehyde (MDA) in
      wer liver tissue samples were examined. The dietary alpha-tocopherol intake and
      its plasma changes in LDA cows were also investigated. Cows were divided into
      four groups according to their liver triglyceride contents (< 20; 20-80; > 80
      mg/g of fresh tissue; and control groups). The lowest plasma vitamin E and the
      highest liver vitamin E levels were found in cows with highest hepatic
      triglyceride content. The highest increase in plasma alpha-tocopherol within 5
      days was seen in cows with the lowest liver triglyceride (P < 0.01). The liver
      triglyceride was positively correlated with liver MDA (r = 0.38; P < 0.05) and
      negatively with plasma alpha-tocopherol (r = -0.41; P < 0.01).

PMID- 9284635
TI  - Changes of blood metabolites and hormones in breeding calves associated with
      weaning.
AB  - Changes of blood metabolites and hormones were studied in female breeding calves
      before, during and after weaning from 4 to 18 weeks of age. Calves were initially
      fed increasing amounts of whole milk (up to 7 kg/day in week 8 of life). Milk
      intake was then gradually decreased up to the age of 16 weeks, when calves were
      completely weaned and only fed hay and concentrates. Average daily gain was 0.85
      kg. Postprandial concentrations of glucose, insulin, insulin-like growth factor-I
      and 3.5.3'-triiodothyronine concentrations gradually decreased (P < 0.05) with
      age, while those of beta-hydroxybutyrate, protein, albumin, haemoglobin and iron
      increased (P < 0.05). Concentrations of cholesterol transiently increased,
      whereas those of urea reversibly decreased. Non-esterified fatty acids,
      triglycerides and growth hormone did not consistently change during the duration
      of the study. In conclusion, changes of glucose, beta-hydroxybutyrate,
      haemoglobin, iron, insulin, insulin-like growth factor-I and 3.5.3'
      triiodothyronine were markedly different from those usually seen in veal calves
      of the same age.

PMID- 9284636
TI  - Evaluation of three pancreas specific protein assays, TLI(trypsin-like
      immunoreactivity), PASP (pancreas specific protein) and CA 19-9 (glycoprotein)
      for use in the diagnosis of canine pancreatitis.
AB  - Three radioimmunoassays (RIA) for the pancreas specific proteins TLI, PASP and CA
      19-9 were evaluated in serum from normal control dogs (n = 40) and dogs with
      pancreatitis (n = 20). Statistically significant differences (P < 0.05) were
      found for serum TLI and PASP levels between the control and pancreatitis groups.
      However, only 3/20 dogs with pancreatitis had serum TLI concentrations greater
      than the highest concentration in control dogs. Concentrations of PASP in serum
      were higher in 15/20 dogs with pancreatitis than in the control dogs. The
      magnitude of the increase in concentrations of PASP in pancreatitis was small in
      the majority of cases. Thus these assays are of limited clinical value in the
      diagnosis of pancreatitis. There was no cross-reactivity with dog serum in the CA
      19-9 assay.

PMID- 9284637
TI  - Epithelial neoplasms of the skin, the cutaneous mucosa and the transitional
      epithelium in dogs: an immunolocalization study for papillomavirus antigen.
AB  - In order to study the prevalence of papillomavirus antigen in canine epithelial
      neoplasms, 535 neoplastic and hyperplastic specimens of the skin, the cutaneous
      mucosa and the transitional epithelium were immunohistochemically stained with a
      polyclonal antiserum against papillomavirus antigen. A positive staining result
      occurred in 44.2% in a total of 95 papillomas and in 27% of 100 diagnosed
      squamous cell carcinomas, other tumours did not react with the applied antiserum.
      Papillomavirus antigen was detectable in 54.2% of all oral and ocular papillomas
      and in 37.0% of all cutaneous papillomas. The majority of the squamous cell
      carcinomas with detectable papillomavirus antigen were considered positive but
      not without restrictions. The average age of dogs with viral oral and ocular
      papillomas was 2.3 years, with viral cutaneous papillomas it was 3.2 years. The
      average age of dogs with virus-positive squamous cell carcinomas was nearly 11
      years. Papillomavirus-like particles were demonstrated by means of transmission
      electron microscopy in three positive oral papillomas, in the positive squamous
      cell carcinomas virion detection failed.

PMID- 9284638
TI  - Short biography of Raymond Jeener (1904-1995).

PMID- 9284639
TI  - The impact of the Rouge-Cloitre as seen by a geneticist.

PMID- 9284640
TI  - Working at the Rouge-Cloitre: a personal account.

PMID- 9284641
TI  - Exploratory experimentation and the role of histochemical techniques in the work
      of Jean Brachet, 1938-1952.

PMID- 9284642
TI  - Cytoplasmic particles in Brussels (Jean Brachet, Hubert Chantrenne, Raymond
      Jeener) and at Rockefeller (Albert Claude), 1935-1955.

PMID- 9284644
TI  - Contributions of the 'Rouge-Cloitre group' to the notion of 'messenger RNA'.
AB  - Most biographical and historical works agree on a common scheme and a few
      'founding papers' for the 'discovery' of mRNA. However, a closer scrutiny of
      these 'founding papers' leads to several unresolved questions with respect to the
      origin of the notion of mRNA. This paper focuses on the analysis of a set of
      contributions made by the group of the Rouge-Cloitre in order to fill in some of
      the remaining gaps in the 'standard history'.

PMID- 9284643
TI  - Jean Brachet, l'heredite generale and the origins of molecular embryology.
AB  - Jean Brachet's research on microsomes and the role of RNA in protein synthesis
      during the 1940s and 50s is placed in the context of embryological views about
      the role of the cytoplasm in development, and plasmagene theory based on studies
      of non-Mendelian inheritance in microorganisms. I show how Brachet's subsequent
      conception of messenger RNA evolved in the context of his conceptions of the
      relations between plasmagenes and nuclear genes. His theorizing on cytoplasmic
      organelles and viruses is further situated in the bio-political controversy over
      the inheritance of acquired characteristics during the Lysenko controversy.

PMID- 9284645
TI  - Interview of Jean Brachet by Jan Sapp. Arco Felice, Italy, December 10, 1980.

PMID- 9284646
TI  - Some archival resources on the Rouge-Cloitre group.

PMID- 9284647
TI  - Effects of combined exposure to noise and toxic substances--critical review of
      the literature.
AB  - A number of studies have been conducted in recent years investigating the
      potential effects on various health endpoints of the combination of noise and a
      variety of different industrial substances. This review indicates that the
      information available in both animals and humans on this subject is limited
      particularly with respect to assessing occupational risk. Most studies have
      focused on auditory effects in animals, although investigations have been
      performed for other toxicological endpoints. For some substances, notably
      toluene, the information from animals studies does suggest an interaction but
      these were performed only at exposure levels to both noise and chemicals which
      were each individually ototoxic. Single simultaneous exposure to noise and
      styrene did not result in any enhancement of auditory impairment above that
      produced by noise or styrene alone. Single simultaneous exposure to noise and
      carbon monoxide (CO), however, showed some evidence of enhancement of ototoxicity
      beyond that produced by noise or carbon monoxide alone, although only at high
      atmospheric concentrations of CO. When 1,3-dinitrobenzene was administered
      parentally at neurotoxic dose levels with continuous noise exposure, there was an
      increased severity of effects in the brain stem. Combined exposure to noise and
      lead and/or cadmium resulted in histopathological heart lesions of undefined
      severity, a finding which was not observed for either of those agents in
      isolation. Dermal exposure to dimethylformamide and noise or inhalation exposure
      to xylene and noise resulted in some biochemical changes in cardiac muscle which
      were of doubtful toxicological significance. In developing mice, there was
      evidence that combined exposure to cadmium sulphate and noise caused an increased
      incidence of external and skeletal malformations but only at dose levels of
      cadmium which would have induced developmental effects. Overall, for each of
      these chemicals and endpoints observed there is a suggestion of some interaction
      with noise exposure. From the data that are currently available, however,
      inferences cannot be drawn on whether or not interactions would have occurred at
      lower, more occupationally relevant, levels of exposure. A number of studies have
      investigated human populations exposed to both noise and industrial chemicals.
      Due to confounding factors, however, it was concluded that these data were
      inadequate for assessing the combined effects of noise and chemical exposure on
      hearing.

PMID- 9284648
TI  - A comprehensive strategy for the assessment of noise exposure and risk of hearing
      impairment.
AB  - A comprehensive strategy is presented for the evaluation of the daily noise
      exposure level [LEX,d in dB(A)] and the assessment of the risk of hearing
      impairment. The risk is defined as the probability for a worker with a given
      exposure history to noise to develop a hearing deficit above a given threshold.
      It is shown that for a given accuracy to be obtained on the risk prediction, the
      precision required on the LEX,d is low at levels around 90 dB(A) and increases at
      higher levels. The strategy uses the concepts of homogeneous group of exposure
      (HGE) and stationarity interval (S.I.), defined as the period over which the
      exposure distribution is the same for the members of the HGE. The number of
      workers to sample, the number of samples to take for each worker and their
      duration are discussed. A semi-random sampling is recommended, excluding the
      periods with low noise exposure. Tests are proposed for the homogeneity of the
      group and the validity of the S.I.. A corrected standard deviation is defined in
      order to take into account the skewness of the distribution of the noise
      equivalent levels of the samples and formulas are presented to estimate the
      LEX,d, its standard error and the corresponding risk of hearing impairment.

PMID- 9284649
TI  - The variability of exposure over time: a prospective longitudinal study.
AB  - Four hundred and forty personal air measurements were carried out on 54 workers,
      employed in the main processes in six different factories (6-13 in each).
      Potential exposure was to lead, benzene and dust. Ten randomly repeated hygiene
      surveys were carried out over 1 year. In order to estimate the magnitude of the
      variability in workers' exposure over time, its sources, the variance between
      workers and the variance within a worker, a nested unbalanced analysis-of
      variance model was fitted to the log-transformed data. Of the total exposure
      variance, the within variance of a worker's exposure over time was 51%
      (geometrical standard deviation, GSD = 3.1) and the between workers, factories
      and air contaminants variance was 49%. The exposure variance between all the
      workers was due mainly to variance between workers within the same factory (67%).
      Outdoor locations, mobility of the worker and mobility of the sources of exposure
      result in a positive influence on both the variance between (26%, ANOVA) and the
      variance of a worker over time (39%, regression). These variables are therefore
      important in the sampling strategy of workers' exposure. For valid compliance
      testing and assessment of workers' exposure the mean and the within- and between
      variance of the workers' exposure over time should be considered. The exposure
      should be measured several times a year randomly in order to prevent workers
      misclassification. To assess yearly exposure, a GSD = 3.1 can be used to
      calculate confidence limits for the arithmetic mean of worker's exposure
      measurements, in circumstances similar to those in this study.

PMID- 9284650
TI  - Tobacco marketing: shackling the pied piper.

PMID- 9284651
TI  - The challenge for Beijing: the 10th world conference on tobacco or health.

PMID- 9284652
TI  - Community institutional care for frail elderly people.

PMID- 9284653
TI  - The demographic timebomb.

PMID- 9284654
TI  - Children with obsessive compulsive disorder.

PMID- 9284655
TI  - American Medical Association endorses consumer products.

PMID- 9284656
TI  - Drugs must be tested for use in children.

PMID- 9284657
TI  - Police free to bug surgeries.

PMID- 9284658
TI  - FDA tightens rules on advertising.

PMID- 9284659
TI  - The campaigner who dreams of a tobacco free world.

PMID- 9284660
TI  - Size at birth, maternal nutritional status in pregnancy, and blood pressure at
      age 17: population based analysis.
AB  - OBJECTIVE: To assess the effect of size at birth, maternal nutrition, and body
      mass index on blood pressure in late adolescence. DESIGN: Population based
      analysis of birth weight corrected for gestational age, mother's weight before
      pregnancy and weight gain in pregnancy, obtained from the Jerusalem perinatal
      study, and blood pressure and body mass index at age 17, available from military
      draft records. SETTING: Jerusalem, Israel. SUBJECTS: 10,883 subjects (6684 men
      and 4199 women) born in Jerusalem during 1974-6 and subsequently drafted to the
      army. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressures measured at
      age 17 and their correlation with birth weight, size at birth, mother's body mass
      index and weight gain during pregnancy, and height and weight at age 17. RESULTS:
      Systolic and diastolic blood pressures were significantly and positively
      correlated with body weight, height, body mass index at age 17, and with mother's
      body weight and body mass index before pregnancy, but not with birth weight or
      mother's weight gain in pregnancy. CONCLUSION: Variables reflecting poor
      intrauterine nutrition, including low maternal body mass index before pregnancy,
      poor maternal weight gain in pregnancy, and being born small for gestational age,
      were not associated with a higher blood pressure in late adolescence.

PMID- 9284662
TI  - Are drug advertisements in Indian edition of BMJ unethical?

PMID- 9284661
TI  - Management of chronic hepatitis C: clinical audit of biopsy based management
      algorithm.
AB  - OBJECTIVE: To assess the attendance, outcome, compliance with treatment, and
      response to interferon alfa in patients with chronic hepatitis C who attended
      during 1995 and were treated according to a biopsy based algorithm. DESIGN:
      Retrospective audit of all patients with chronic hepatitis C attending outpatient
      clinics over one year. SETTING: The liver unit at a London teaching hospital.
      SUBJECTS: 255 patients with chronic hepatitis C. MAIN OUTCOME MEASURES: Patient
      survival, attendance, and compliance with diagnostic and therapeutic regimens.
      Response to interferon alfa treatment, based on loss of viraemia three months
      after cessation of treatment. RESULTS: A large proportion of patients (39%) with
      newly diagnosed chronic hepatitis C infection do not want to undergo further
      investigation. Of those patients who do attend for further treatment, a large
      proportion with severe hepatic fibrosis (42%) do not want to undergo currently
      available treatment. The response rate to interferon (21%) in treated patients
      was similar to that previously reported in a trial setting. There was no
      significant difference in response rates in patients with or without severe
      fibrosis not amounting to cirrhosis. In patients with cirrhosis there was a high
      incidence of hepatocellular carcinoma (18%) over a follow up period of 20 months.
      CONCLUSION: Current strategies aimed at investigating and treating patients with
      chronic hepatitis C are not acceptable to a large proportion of patients. Many
      patients with cirrhosis related to hepatitis C infection develop hepatic
      neoplasms, and management strategies to deal with this problem are urgently
      required.

PMID- 9284663
TI  - Commentary: advertising adversities.

PMID- 9284664
TI  - A randomised comparison of the EuroQol and Short Form-36 after stroke. United
      Kingdom collaborators in the International Stroke Trial.

PMID- 9284665
TI  - Cognitive impairment in elderly people: population based estimate of the future
      in England, Scotland, and Wales.

PMID- 9284666
TI  - Successful breast feeding while mother was taking cyclosporin.

PMID- 9284667
TI  - Generalised pruritus associated with amlodipine.

PMID- 9284668
TI  - Withdrawal of long-term diuretic medication in elderly patients: a double blind
      randomised trial.
AB  - OBJECTIVES: About 20% of elderly people use long-term diuretic medication, but
      there is doubt whether prolonged diuretic medication on such a large scale is
      necessary. We performed a study to assess what proportion may successfully be
      withdrawn from diuretic therapy. DESIGN: Double blind randomised controlled trial
      with six month follow up. SETTING: General practice. SUBJECTS: 202 patients
      taking long-term diuretics without manifest heart failure or hypertension.
      INTERVENTIONS: Patients were allocated to either placebo (withdrawal group, n =
      102) or continuation of diuretic treatment (control group, n = 100). MAIN OUTCOME
      MEASURE: Occurrence of clinical conditions requiring diuretic therapy based on
      fixed criteria. RESULTS: During follow up diuretic therapy was required in 50
      patients in the withdrawal group and 13 in the control group (risk difference
      36%; 95% confidence interval 22% to 50%). Heart failure was the most frequent
      cause of prescribing diuretic therapy (n = 25). Cessation of diuretic therapy
      caused a mean increase in systolic blood pressure of 13.5 (9.2 to 17.8) mm Hg and
      in diastolic pressure of 4.6 (1.9 to 7.3) mm Hg. CONCLUSION: Withdrawal of long
      term diuretic treatment in elderly patients leads to symptoms of heart failure or
      increase in blood pressure to hypertensive values in most cases. Any attempt to
      withdraw diuretic therapy requires careful monitoring conditions, notably during
      the initial four weeks.

PMID- 9284669
TI  - Osteoporosis.

PMID- 9284670
TI  - ABC of mental health. Mental health in a multiethnic society.

PMID- 9284671
TI  - An "ecological" approach to the obesity pandemic.

PMID- 9284672
TI  - How to read a paper. Papers that report drug trials.

PMID- 9284673
TI  - Intersalt data. Cross cultural studies such as Intersalt study cannot be used to
      infer causality.

PMID- 9284674
TI  - Intersalt data. Data linking sodium intake to subsequent morbid and fatal
      outcomes must be studied.

PMID- 9284675
TI  - Intersalt data. Conclusions drawn in paper "revisiting" Intersalt data are of
      questionable validity.

PMID- 9284676
TI  - Intersalt data. Epidemiological studies should be designed to reduce correction
      needed for measurement error to a minimum.

PMID- 9284677
TI  - Intersalt data. Correction for regression dilution bias in Intersalt study was
      misleading.

PMID- 9284678
TI  - Intersalt data. Slow decremental change in dietary sodium load in whole
      populations is needed.

PMID- 9284679
TI  - Intersalt data. Science demands data sharing.

PMID- 9284680
TI  - Intersalt data. Collaborative efforts must be made to reduce sodium in diet.

PMID- 9284681
TI  - Intersalt data. Sodium contents of restaurant foods in United States are high.

PMID- 9284682
TI  - Women's autonomy in childbirth. Courts should also take evidence from obstetric
      anaesthetists.

PMID- 9284683
TI  - Women's autonomy in childbirth. An absurd law that needs changing.

PMID- 9284684
TI  - General anaesthesia does not usually affect the fetus.

PMID- 9284685
TI  - Prophylactic and empirical antifungal treatment in cancer complicated by
      neutropenia. Combining different antifungal strategies in same systematic review
      is inappropriate.

PMID- 9284686
TI  - Cooperation between pharmacists and general practitioners benefits patients.

PMID- 9284687
TI  - Cycling offers important health benefits and should be encouraged.

PMID- 9284688
TI  - Changes in population distribution of sense of coherence do not explain changes
      in overall mortality.

PMID- 9284689
TI  - Treating hypothyroidism. Biochemical tests are important in diagnosis.

PMID- 9284690
TI  - Treating hypothyroidism. Threshold of thyroid stimulating hormone should be
      higher before treatment is started.

PMID- 9284691
TI  - Test sales do not have impact on prevalence of smoking by children.

PMID- 9284692
TI  - Internet is useful for information on rare conditions.

PMID- 9284693
TI  - Clinical review 90: Leptin and clinical medicine: a new piece in the puzzle of
      obesity.

PMID- 9284694
TI  - Acromegaly.

PMID- 9284695
TI  - Evolving toward a new paradigm for prevention of osteoporosis--the time is upon
      us.

PMID- 9284696
TI  - Prevention of early postmenopausal bone loss with cyclical etidronate therapy (a
      double-blind, placebo-controlled study and 1-year follow-up)
AB  - The objective of the study was to evaluate the effects of cyclical therapy with
      etidronate and calcium on spinal and femoral bone loss in the early post
      menopausal period. Fifty-four women, 53 +/- 2.8 yr old (mean +/- SD) and 2.3 +/-
      1.3 yr post menopause received oral doses of either 400 mg/day etidronate for 2
      weeks followed by 500 mg/day elemental calcium for 11 weeks, or placebo for 14
      days followed by calcium for 11 weeks, repeated over a total of 24 months. A
      statistically significant increase in spinal bone mineral density (BMD) was
      observed after 6 months in the etidronate group. At 2 yr, the mean treatment
      differences in spinal and femoral neck BMD were +2.93% (P < 0.02) and 2.02% (P <
      0.03), respectively. Serum osteocalcin and urinary crossLaps/creatinine excretion
      were decreased significantly by etidronate. Etidronate was well tolerated with a
      safety profile similar to that of placebo. Thirty-seven women participated in a 1
      yr open-label follow-up study. Twelve months after treatment withdrawal, spinal
      BMD in the former etidronate group decreased by 1.43% and serum osteocalcin and
      urinary crossLaps returned to pretreatment values. In conclusion, cyclical
      etidronate is an effective therapy for the prevention of both trabecular and
      cortical bone loss in the early menopause and has a good safety profile.

PMID- 9284697
TI  - Idiopathic osteoporosis--is the osteoblast to blame?

PMID- 9284698
TI  - Reduced serum levels of the growth hormone-dependent insulin-like growth factor
      binding protein and a negative bone balance at the level of individual remodeling
      units in idiopathic osteoporosis in men.
AB  - Idiopathic osteoporosis in younger individuals could be related to reduced bone
      formation rather than increased bone resorption, and disturbances in GH or
      insulin-like growth factor (IGF)-I production could be involved in its
      pathogenesis. In the present study, men with idiopathic osteoporosis were
      compared with healthy men, with respect to bone histomorphometry and to serum
      levels of IGF-I, IGF-II, IGF binding protein (IGFBP)-2 and IGFBP-3, and 24-h
      urinary excretion of GH. Mean wall thickness was reduced in the patients (48.3 +/
      7.2 vs. 61.7 +/- 5.4 microns, P < 0.001). Also, resorption depth was decreased,
      albeit to a lesser degree (54.4 +/- 3.8 vs. 60.7 +/- 5.3 microns, P < 0.01), thus
      creating a pronounced negative balance (-6.04 +/- 9.8 vs. 0.96 +/- 3.2 microns, P
      < 0.05). In the patients, serum concentrations of IGFBP-3 were reduced, compared
      with controls, with a 46% lower mean value; whereas levels of IGF-I, IGF-II,
      IGFBP-2, and GH were similar in the two groups. Thus, there was a significant
      negative balance caused by a pronounced decrease in wall thickness in men with
      idiopathic osteoporosis. The finding of low IGFBP-3 levels in these patients is
      interesting, in view of previous clinical and experimental findings, but its
      pathophysiological significance remains to be determined.

PMID- 9284699
TI  - Insulin-like growth factor-I in men with idiopathic osteoporosis.
AB  - The etiology of osteoporosis in most men without a history of alcohol abuse,
      hypogonadism, or glucocorticoid excess is unknown. Several histomorphometric
      reports have demonstrated a reduction in indices of bone formation. We tested the
      hypothesis that the putative reduction in bone formation in men with idiopathic
      osteoporosis may be related to deficiencies in skeletal mechanisms that are
      mediated by insulin-like growth factor I (IGF-I). Twenty-four middle-aged men
      (50.5 +/- 1.9 yr) with severe idiopathic osteoporosis (mean lumbar spine T-score 
      3.5 +/- 0.16) were studied. The following biochemical indices were all normal:
      serum calcium, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, testosterone,
      osteocalcin, carboxyterminal propeptide of type I collagen, bone specific
      alkaline phosphatase, urinary calcium, and collagen crosslinks. Parathyroid
      hormone level was in the lower range of normal, 25 +/- 2 pg/mL (nl: 10-65). Mean
      serum IGF-I level was also in the lower range of normal, 157.9 +/- 7.6 ng/mL
      (normal age-matched range, 140-260 ng/mL). Eight men had IGF-I levels that were
      below 140 ng/mL. The mean IGF-IZ score was -0.75, significantly different from
      the expected mean of zero (P = 0.0002). IGF-I was correlated negatively with age
      (r = -0.49, P < 0.02). With age held constant, serum IGF-I accounted for 15% of
      the variance in lumbar bone mineral density (BMD; P < 0.001). The osteocalcin
      concentration correlated well with bone density at the distal 1/3 radius (r =
      +0.44; P < 0.002). Histomorphometric analysis of bone biopsy specimens showed
      significant reductions in cancellous bone volume (31%; P < 0.001), cortical width
      (28%; P < 0.05), osteoid surface (33%; P < 0.01), and bone formation rate (54%; P
      < 0.01) when results were compared with age-matched control subjects. Percent
      eroded surface was normal and was correlated inversely with serum IGF-I levels (r
      = -0.5; P < 0.04). These results suggest that serum IGF-I levels are reduced in
      men with idiopathic osteoporosis and that IGF-I correlates with and may
      contribute to the reduction in lumbar spine bone mass density (BMD). The low IGF
      I levels may reflect the reduction in bone formation demonstrated by
      histomorphometry. Insights into the etiology of idiopathic osteoporosis in men
      may be revealed by further studies of the IGF-I axis.

PMID- 9284700
TI  - The interface between diabetic retinopathy, diabetes management, and insulin-like
      growth factors.

PMID- 9284701
TI  - Free and total insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP
      1), and IGFBP-3 and their relationships to the presence of diabetic retinopathy
      and glomerular hyperfiltration in insulin-dependent diabetes mellitus.
AB  - The existing literature on serum insulin-like growth factor I (IGF-I) levels in
      insulin-dependent diabetes mellitus (IDDM) is conflicting. Free IGF-I may have
      greater physiological and clinical relevance than total IGF-I. Recently, a
      validated method has been developed to measure free IGF-I levels in the
      circulation. Serum free and total IGF-I, IGF-binding protein-1 (IGFBP-1), and
      IGFBP-3 levels were measured in 56 insulin-treated IDDM patients and 52 healthy
      sex- and age-matched controls. Diabetic retinopathy was established by direct
      fundoscopy. In 54 IDDM patients, the glomerular filtration rate (GFR) and
      effective renal plasma flow were calculated from the clearance rate of
      [125I]iothalamate and [131I]iodohippurate sodium. Fasting free IGF-I, total IGF
      I, and IGFBP-3 levels were significantly lower in IDDM patients than in age- and
      sex-matched healthy controls (free IGF-I, P < 0.005; total IGF-I, P < 0.001;
      IGFBP-3, P = 0.001), whereas IGFBP-1 levels were higher (P < 0.001). In IDDM
      subjects, decreases in free IGF-I, total IGF-I, and IGFBP-3 levels with age were
      observed (free IGF-I, r = -0.27 and P = 0.05; total IGF-I, r = -0.52 and P <
      0.001; IGFBP-3, r = -0.37 and P = 0.005). Free IGF-I was inversely related to
      fasting glucose in IDDM subjects (r = -0.35; P = 0.01), whereas the relationship
      between total IGF-I and fasting glucose did not reach significance (r = -0.27; P
      = 0.06). Age-adjusted free IGF-I levels were significantly higher (P < 0.05) in
      IDDM subjects with retinopathy than in subjects without retinopathy after
      adjustment for age. Total IGF-I and IGFBP-3 levels were positively related to GFR
      (total IGF-I, r = 0.35 and P < 0.05; IGFBP-3, r = 0.28 and P < 0.05). Both of
      these differences lost significance after adjustment for age. Free IGF-I, total
      IGF-I, and IGFBP-3 levels were lower and IGFBP-1 levels were higher in insulin
      treated IDDM subjects compared to those in age- and sex-matched controls. Free
      IGF-I, total IGF-I, and IGFBP-3 levels decreased significantly with age in IDDM
      subjects. Age-adjusted free IGF-I levels in subjects with diabetic retinopathy
      were higher than those in subjects without diabetic retinopathy. Total IGF-I and
      IGFBP-3 levels were positively related to GFR in IDDM subjects, but these
      relations were lost after adjustment for age. Measurement of serum free IGF-I
      levels in IDDM subjects did not have clear advantages compared to that of total
      IGF-I, IGFBP-1, and IGFBP-3 levels. Serum IGF-I and IGFBPs reflect their tissue
      concentrations to a various degree. Consequently, extrapolations concerning the
      pathogenetic role of the IGF/IGFBP system in the development of diabetic
      complications at the tissue level remain speculative.

PMID- 9284702
TI  - An unusual treatment-related complication in a patient with growth hormone
      secreting pituitary tumor.

PMID- 9284703
TI  - Augmentation of bone mineral density in hirsute women.
AB  - Hirsutism is associated with both hyperandrogenism and oligomenorrhea or
      amenorrhea, which have opposing effects on bone mineral density (BMD). We tested
      the hypothesis that hyperandrogenism in hirsute women counteracts the osteopenic
      effects of menstrual dysfunction. Using dual energy x-ray absorptiometry, we
      measured BMD and total bone mineral content (BMC) in 32 young women referred for
      hirsutism. The control group consisted of 25 matched, nonhirsute women. Among the
      hirsute women, 21 reported regular menses, and 11 gave a history of
      oligomenorrhea; all members of the control group reported regular menses.
      Compared with controls, hirsute women had higher total BMD (1.202 +/- 0.02 vs.
      1.116 +/- 0.02 g/cm2, P < 0.01), lumbar spine BMD (1.183 +/- 0.02 vs. 1.125 +/-
      0.02 g/cm2, P < 0.01), and total BMC (2700 +/- 66 vs. 2400 +/- 70 g, P < 0.001).
      Serum total testosterone levels were similar, but androstenedione levels were
      higher (11.7 +/- 0.80 vs. 7.9 +/- 0.79 nmol/L, P < 0.005) and sex hormone binding
      globulin levels lower (22.0 +/- 3.0 vs. 57.6 +/- 8.5 nmol/L, P < 0.001) in
      hirsute women than controls. Oligomenorrheic hirsute women had higher BMD than
      nonhirsute women, although the augmentation was less pronounced than in
      eumenorrheic hirsute women. These results indicate that hirsutism is associated
      with higher bone density and mineral content, consistent with a net positive
      effect of hyperandrogenism on skeletal mass.

PMID- 9284704
TI  - Diabetes and mitochondrial encephalomyopathy with lactic acidosis and stroke-like
      episodes (MELAS): radiolabeled polymerase chain reaction is necessary for
      accurate detection of low percentages of mutation.
AB  - A 6-yr-old boy presented with muscle weakness, lactic acidemia, and insulin
      dependent diabetes mellitus (IDDM). Using PCR and restriction enzyme analysis, he
      was found to have the classical A3248G mitochondrial DNA (mtDNA) mutation
      frequently associated with mitochondrial encephalomyopathy with lactic acidosis
      and stroke-like episodes (MELAS). The mutation was confirmed by sequencing muscle
      mtDNA. The mutation in mtDNA from muscle, lymphoblasts, and blood was clearly
      demonstrable by standard methods using ethidium bromide staining. His mother also
      had IDDM, but no A3243G mutation could be detected in her blood or transformed
      lymphoblasts using the same PCR technique. When PCR was carried out in the
      presence of [32P]deoxycytidine triphosphate, subsequent autoradiography detected
      the presence of the mutation at low levels in mtDNA from the mother's
      lymphoblasts and blood. Study of the mother's muscle showed a mitochondrial
      myopathy, despite the fact that she was asymptomatic. We emphasize that the
      increased sensitivity of radiolabeled PCR may be necessary to detect small
      percentages of heteroplasmic A3243G mtDNA mutation in blood from diabetic
      subjects. Otherwise the incidence of mtDNA mutations in both IDDM and non-insulin
      dependent diabetes may be underestimated.

PMID- 9284705
TI  - Impaired postprandial regulation of insulin-like growth factor binding protein-1
      in children with chronic renal failure.
AB  - Patients with chronic renal failure (CRF) have elevated plasma levels of insulin
      like growth factor-1 (IGFBP-1). We sought to determine the dynamics of plasma
      IGFBP-1 in response to an endogenous insulin pulse during an oral glucose
      tolerance test (oGTT) in 12 prepubertal children with advanced CRF [glomerular
      filtration rate (GFR) 12.5 +/- 4 mL/min/1.73 m2] and in 9 age-, gender-, and body
      size-matched controls with normal renal function. Glucose and insulin responses
      to oGTT were significantly elevated in CRF (P < 0.01), indicating decreased
      sensitivity to the hypoglycemic action of insulin. Fasting plasma IGFBP-1 levels
      in CRF (235 +/- 40 ng/mL) were 2.5-fold increased compared with controls (94 +/-
      11.6 ng/mL, P < 0.0001). In controls, plasma IGFBP-1 levels rapidly decreased
      with time by 52%, to a level of 45 +/- 6.7 ng/mL 180 min after the oral glucose
      load. In contrast, plasma IGFBP-1 levels in CRF patients slowly decreased with
      time by 25%, to a level of 176 +/- 28 ng/mL (P < 0.001 vs. controls) 180 min
      after the oral glucose load. For the group as a whole, the percent decrease in
      IGFBP-1 at 180 min was positively correlated with GFR (r = 0.85, P < 0.0001).
      Plasma GH concentrations were not statistically different at baseline, but showed
      a paradoxical increase in CRF patients thereafter. Plasma IGF-I concentrations at
      baseline were comparable in CRF patients and controls and similarly decreased by
      about 10% (P < 0.01) after the oral glucose load. In summary, our study shows
      that the decline of plasma IGFBP-1 in response to an oral glucose load is
      impaired in children with CRF despite increased insulin levels. This impaired
      postprandial decline of plasma IGFBP-1 might interfere with glucose homeostasis
      by blocking insulin-like activity of free IGFs in vivo and thereby contribute to
      glucose intolerance in uremia.

PMID- 9284706
TI  - Recombinant human thyrotropin is a potent stimulator of thyroid function in
      normal subjects.
AB  - Recombinant human TSH (rhTSH) is known to stimulate 131I uptake and thyroglobulin
      (Tg) release from the postoperative remnant and metastases in thyroid cancer
      patients, but its effects on serum thyroid hormone and Tg concentrations in
      normal subjects have not been reported. Before using rhTSH in the management of
      thyroid disorders other than cancer, the thyroid response to rhTSH in normal
      subjects must be assessed. Six subjects, two men and four women, without evidence
      of thyroid disease, including normal serum free T4 index and TSH concentrations
      and negative tests for antithyroid peroxidase and Tg, were studied. Each received
      0.1 mg rhTSH, im, 11% of the lowest dose that has been administered to thyroid
      cancer patients. Blood was obtained before; 2, 4, and 8 h after; and 1, 2, 3, 4,
      7, and about 3 weeks after rhTSH administration. Serum TSH significantly
      increased at 2 h (mean +/- SE, 2.4 +/- 0.9 to 40.7 +/- 7.4 mU/mL), peaked at 4 h
      (50.9 +/- 9.3), remained significantly elevated for 1 day, and was significantly
      below baseline (0.8 +/- 0.5) 7 days after rhTSH administration. Serum T3
      increased significantly at 4 h (115 +/- 4 to 190 +/- 14 ng/dL), peaked at 24 h
      (217 +/- 23 ng/dL), and remained significantly elevated for 3 days (151 +/- 12
      ng/dL). Serum T4 increased significantly at 8 h (7.3 +/- 0.2 to 9.8 +/- 0.4
      micrograms/dL), peaked at 24 h (11.2 +/- 0.5 micrograms/dL), and remained
      significantly elevated for 4 days (9.4 +/- 0.5 micrograms/dL). Serum Tg did not
      change for the first 8 h, increased significantly at 1 day (15.9 +/- 3.9 to 34.7
      +/- 6.0 ng/mL), peaked at 2 days (44.2 +/- 7.0 ng/mL), and remained significantly
      elevated for 4 days (37.7 +/- 13.7 ng/mL). All values returned to baseline at 3
      weeks. TSH antibodies were not detected at 3 weeks. A single dose of 0.1 mg rhTSH
      is a potent stimulator of thyroid function in normal subjects. rhTSH may be a
      useful agent to test thyroid reserve and for use in clinical settings that
      require direct thyroid stimulation.

PMID- 9284707
TI  - Maternal iodine status and thyroid volume during pregnancy: correlation with
      neonatal iodine intake.
AB  - Differences in pregnancy-associated alterations in thyroid volume and urinary
      iodine (UI) excretion have been attributed to geographical variations in dietary
      iodine intake. In this study, ultrasound-measured thyroid volume and UI excretion
      were assessed during the 3 trimesters of pregnancy, at delivery, and at 6 weeks
      postpartum. Urine specimens also were obtained from mothers and both breast- and
      formula-feeding infants at 3 days after delivery. Thyroid volume showed a
      significant increase (maximum 47.0%), compared with nonpregnant control values
      over the 3 trimesters of pregnancy, which occurred as early as the first
      trimester and was paralleled by increased UI excretion, followed in turn by a
      precipitous fall at delivery. UI excretion in breast-feeding neonates (100 +/-
      6.8 micrograms/L) was significantly higher than in their mothers (76 +/- 5.6
      micrograms/L; p < 0.01) but was significantly lower (43 +/- 3.5 micrograms/L) in
      formula-fed infants. The results suggest that in an area of moderate dietary
      iodine intake, UI loss during pregnancy may result in maternal thyroid
      enlargement. The ability of the breast to transport iodine compensates for this
      loss in breast-fed infants, but this protection may be lost in formula feeding.

PMID- 9284708
TI  - Alterations in parathyroid dynamics in lithium-treated subjects.
AB  - Chronic lithium (Li) therapy, used extensively in the treatment of bipolar
      affective disorders, is one of psychiatry's most effective treatments. The data
      on the effects of Li on baseline PTH and calcium (Ca) levels are conflicting. A
      clear resetting of the PTH set-point to the right was documented in vitro;
      however, the effect of Li on the Ca-PTH axis has not been rigorously studied in
      vivo. In this study, we used a Ca and citrate infusion protocol to fully
      characterize PTH dynamics in seven female patients, 40 +/- 11 yr old, on chronic
      Li therapy for 5.23 +/- 4.0 yr, compared with seven controls, 41 +/- 16 yr old
      (mean +/- SD). Baseline ionized Ca (Cai) and intact PTH levels were 5.2 +/- 0.06
      mg/dL and 38.4 +/- 5.7 pg/mL in the Li group and 4.9 +/- 0.06 mg/dL and 21.2 +/-
      5.0 pg/mL in the controls, (mean +/- SEM) P = 0.008 and 0.042, respectively. We
      defined an inverse sigmoidal curve between Cai and the intact biologically active
      PTH molecule (iPTH) for the two study groups and demonstrated a significant shift
      in the iPTH set-point to the right in the Li-treated patients, compared with
      controls. The set-point was 5.08 +/- 0.04 for the former group and 4.88 +/- 0.04
      mg/dL for the latter, P = 0.004. Patients on Li had significantly higher Cai
      levels during citrate and Ca infusions, P = 0.0008 and 0.012, respectively;
      however, iPTH levels were not significantly different between the two study
      groups during either infusion. The shift in the iPTH set-point to the right in
      the Li-treated patients and the similar iPTH levels, despite higher serum Cai
      levels during both infusions, establish the presence of a clear alteration in PTH
      dynamics in patients on chronic Li therapy.

PMID- 9284709
TI  - Serum leptin levels in normal children: relationship to age, gender, body mass
      index, pituitary-gonadal hormones, and pubertal stage.
AB  - It is commonly accepted that at least in girls puberty starts when a minimum
      level of body mass or a certain amount of body fat are present. However the
      precise signal by which adipose stores inform the hypothalamus of the degree of
      energetic reserves is unknown. Leptin is a hormone produced by the adipocytes to
      regulate food intake and energy expenditure at the hypothalamic level. To
      understand whether leptin is the adipose tissue signal that allows puberty, 789
      normal children of both sexes, age 5-15 yr, were transversally studied. Leptin
      levels, as well as gonadal and gonadotropins, levels, were analyzed in addition
      to the determination of auxological parameters. In an age-related analysis,
      leptin levels in girls rose from 5-15 yr (from 4.3 +/- 0.4 to 8.5 +/- 0.9
      micrograms/L) in parallel with body weight. Boys always had lower leptin levels
      than girls (3.3 +/- 0.3 micrograms/L at 5 yr), but they rose in parallel with
      weight until 10 yr (5.3 +/- 0.7 micrograms/L), when a striking decrease was
      observed until 15 yr (3.0 +/- 0.3 micrograms/L). In girls, leptin was the first
      hormone to rise followed by FSH and later by LH and estradiol. A similar pattern
      occurred in boys, despite the fact that leptin dropped after 10 yr when
      testosterone rises. Divided into three pubertal stages, i.e. P1 = prepuberty, P2
      = early puberty, and P3 = overt puberty, in girls the four hormones rose
      progressively from P1 to P3, but from P2 to P3 the present increment was greater
      for LH and estradiol. In boys, leptin decreased from P1 to P3, whereas FSH, LH,
      and testosterone rose. The age-related changes were not caused by adiposity
      variations, because data did not change when subtracting values of children over
      97% of standard deviation score of body mass index. IN CONCLUSION: 1) leptin
      appears to increase in both boys and girls before the appearance of other
      reproductive hormones related to puberty; 2) leptin levels in boys are always
      lower than in girls, although they increase with age until the age 10 yr; 3)
      leptin in boys declines about the time testosterone increases. Leptin may well be
      a permissive factor for the initiation of pubertal events.

PMID- 9284710
TI  - Effect of birth weight and maternal smoking on cord blood leptin concentrations
      of full-term and preterm newborns.
AB  - Prematurity, maternal smoking, and low birth weight each result in neuroendocrine
      dysfunction and increased perinatal morbidity and mortality. Leptin, an adipocyte
      secreted protein, has provided the first physiological link to the regulatory
      system controlling starvation-induced neuroendocrine changes in rodents. This
      study investigated whether leptin concentrations were detectable in cord blood of
      newborns, and assessed the effect of birth weight, prematurity, and maternal
      smoking on cord blood leptin concentrations. Fifty consecutively enrolled full
      term and 12 preterm newborns born to mothers who smoked during pregnancy were
      compared to 50 full-term and 12 preterm newborns born to parents who were
      nonsmokers. RIA for leptin was performed using cord blood samples collected
      immediately after birth. Leptin concentrations were detectable in newborns and
      correlated positively with obesity (full-term, r = 0.30, P < 0.01; preterm, r =
      0.47, P < 0.05). Maternal smoking during pregnancy was associated with decreased
      leptin concentrations in the cord blood of both full-term and preterm newborns.
      This effect was independent of obesity (full-term newborns: 5.25 +/- 2.48 vs.
      4.21 +/- 2.71 ng/ml, P = 0.01) and was more pronounced in premature newborns
      (5.67 +/- 3.6 vs. 2.46 +/- 2.03, P = 0.02), and its magnitude in full-term
      newborns was directly related to the reported number of cigarettes the mothers of
      the full-term newborns smoked per day (r = -0.438, P < 0.001). Thus, low birth
      weight and maternal smoking are both associated with decreased leptin
      concentrations, and these effects are more pronounced in premature newborns.
      Future studies will be needed to determine whether administration of leptin might
      reverse the neuroendocrine dysfunction caused by maternal smoking.

PMID- 9284711
TI  - Outcome of differentiated thyroid cancer diagnosed in pregnant women.
AB  - The clinical features and outcome of thyroid cancer in 61 pregnant women (mean
      age, 26.0 +/- 5.9 SD yr) and in 528 female, age-matched controls who were not
      pregnant (mean age, 26.3 +/- 5.9 SD yr) were compared. Median follow-up was 22.4
      and 19.5 yr [P = not significant (NS)] in the two groups, respectively. The
      thyroid nodule was asymptomatic and discovered on routine examination more often
      in the pregnant women (74%) than in controls (43%, P < 0.001); other clinical and
      tumor features were similar in the two groups. Most of the pregnant women
      underwent thyroidectomy after delivery (77%) or during the second trimester of
      pregnancy (20%). Near-total thyroidectomy was done in 43 (73%) of the pregnant
      women and 265 (59%) of the controls (P = NS), and nearly the same proportion of
      both groups (30% and 25%, respectively) were treated with 131I postoperatively.
      Outcome in the pregnant women and controls, respectively, was: cancer recurrence
      9 (15%) and 107 (23%, P = NS); distant recurrences 1 (2%) and 12 (3%, P = NS),
      and cancer deaths 0 and 6 (1.2%, P = NS). Outcomes were similar when surgery was
      done during or after pregnancy, despite a longer delay in treatment of the latter
      (1.1 +/- 1.0 vs. 16.1 +/- 19.7 months, P < 0.001). This study suggests that the
      prognosis of differentiated thyroid cancer is the same in pregnant women and
      nonpregnant women of the same age, and that the diagnosis and treatment of
      thyroid cancer occurring during pregnancy can be delayed until after delivery in
      most patients.

PMID- 9284712
TI  - Bone health is not affected by luteal phase abnormalities and decreased ovarian
      progesterone production in female runners.
AB  - The primary purpose of this study was to determine whether decreased ovarian
      progesterone production, associated with short and inadequate luteal phases in
      exercising women, was associated with decreased bone mineral density (BMD) and
      altered bone metabolism. Thirty-three eumenorrheic menstruating women
      participated in this study for 3 months. Subjects were required to collect daily
      urine samples for three consecutive menstrual cycles and have blood and urine
      collected weekly. Daily urine samples were analyzed for free LH, estrone
      conjugates (E1C), and pregnanediol 3-glucuronide (PdG), adjusted for creatinine,
      whereas weekly blood and urine samples were analyzed for bone markers, estradiol,
      progesterone, FSH, and LH. Based on the analyses of these samples, subjects were
      divided into three groups: sedentary ovulatory (SedOvul; n = 9), exercising
      ovulatory (ExOvul; n = 14), and exercising luteal phase defects (ExLPD; n = 10).
      The three groups were matched for age (27.6 +/- 1.0 yr), weight (60.6 +/- 1.9
      cm), and reproductive maturity (14.5 +/- 1.0 yr), PdG production during the
      luteal phase was lower (P = 0.004) in the ExLPD women compared to that in the
      SedOvul group (2.4 +/- 0.4 vs. 5.1 +/- 0.6 ng/mL creatinine, respectively). The
      ExOvul group also had less (P < 0.01) PdG production during the luteal phase (3.5
      +/- 0.3 ng/mL creatinine) compared to the SedOvul group. The total production of
      PdG, as assessed by area under the curve analysis, was also lower (P < 0.001) in
      the ExOvul and ExLPD groups compared to that in the SedOvul group. E1C
      production, however, was not different (P > 0.05) among the groups, except for
      E1C during the early follicular phase, which was lower (P = 0.043) in the ExLPD
      group than that in the SedOvul group. BMD and biochemical markers of bone
      metabolism were unaffected by and not associated with the compromised
      progesterone environment, but BMD values at the proximal femur (r = 0.354; P =
      0.061) and total body (r = 0.359; P = 0.056) were associated with decreased early
      follicular E1C production. We conclude the following. 1) Luteal phase
      disturbances occur independent of training volume, and volume of training does
      not have to be severe to result in menstrual disturbances. 2) As a result of
      exercise, disturbance in progesterone production is not associated with decreased
      bone mass. 3) Long follicular phases are associated with reduced estrogen
      production during the early follicular phase, which are both associated with
      decreased bone mass. 4) Provided the estradiol status is adequately maintained,
      BMD is unaffected by decreased progesterone production associated with short and
      inadequte luteal phases in exercising women.

PMID- 9284713
TI  - Two years of growth hormone (GH) treatment increase isometric and isokinetic
      muscle strength in GH-deficient adults.
AB  - GH deficiency in adults is associated with reduced muscle mass and muscle
      strength. The objective of this trial was to follow the effect of 2 yr of GH
      treatment in GH-deficient adults on muscle performance in relation to a reference
      population. Knee extensor and flexor strengths for isometric and isokinetic
      concentric muscle strength were measured using a Kin-Com dynamometer. Hand-grip
      strength was measured in both hands. The fatigue index was calculated as the
      percent reduction in peak torque at 50 repeated isokinetic knee extensions.
      Superimposed, single twitch electrical stimulation was performed. The GH
      deficient subjects had lower isometric knee extensor, knee flexor, and hand-grip
      strength than the reference population. Two years of GH treatment increased and
      normalized the mean isometric knee extensor and flexor strengths. The concentric
      knee flexor and extensor strength at an angular velocity of pi rad/s increased,
      as did the concentric knee flexor strength at an angular velocity of pi/3 rad/s.
      The increase in muscle strength was more marked in younger patients and in
      patients with lower initial muscle strength than predicted. Quadriceps endurance
      decreased, whereas the effect of superimposing single twitches on isometric
      contraction and hand-grip strength was unaffected by the GH treatment. Two years
      of GH therapy in GH-deficient adults increased and normalized isokinetic and
      isometric muscle strength studied in proximal muscle groups. Hand-grip strength
      and the degree of lack of maximal motor unit activation on voluntary isometric
      knee extensor force did not change. The dynamic local muscle fatigue index
      decreased.

PMID- 9284715
TI  - Growth response to growth hormone (GH) treatment relates to serum insulin-like
      growth factor I (IGF-I) and IGF-binding protein-3 in short children with various
      GH secretion capacities. Swedish Study Group for Growth Hormone Treatment.
AB  - The purpose of the study was to evaluate the relationship between the 1-yr (n =
      193) and 2-yr (n = 128) growth response and the individual serum concentrations
      of insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3)
      before and during GH treatment. Our study group of prepubertal short children had
      from very low to high GH secretory capacity, estimated during an arginine-insulin
      tolerance test, and the ages ranged from 3-15 yr at the start of treatment. Their
      serum levels of IGF-I and IGFBP-3 were low before treatment compared to those in
      an age-related reference group of prepubertal children and increased
      significantly from the start to 1 month of GH treatment. The mean increase in
      height SD score was 0.80 SD score after 1 yr of GH treatment and 1.26 SD score
      after 2 yr, with a wide range. In univariate analyses the highest correlation
      coefficients to the 2-yr growth response were found to be vs. the following
      variables from the start of treatment: IGF-I SD score (r = -0.49), log maximum GH
      concentration (log GHmax) during the arginine-insulin tolerance test (r = -0.47),
      difference between the height SD score of the individual child and the
      midparental height SD score (diffSD score; r = -0.45), IGFBP-3 SD score (r = 
      0.39), age (r = -0.30), short term change in IGFBP-3 SD score (r = 0.37), and IGF
      I SD score (r = 0.34). In multivariate stepwise regression analysis, 41% of the
      variation in the 2-yr growth response could be explained by IGF-I SD score or log
      GHmax together with age at the start of treatment, weight SD score at 1 yr of
      age, and diffSD score. When both IGF-I SD score and GHmax were included and when
      the short term changes in IGF-I SD score were added, 46% and 58% of the
      variation, respectively, could be explained. The regression algorithms using
      different combinations of variables and their corresponding prediction intervals
      are also presented.

PMID- 9284714
TI  - Defective hypothalamic growth hormone (GH)-releasing hormone activity may
      contribute to declining GH secretion with age in man.
AB  - There is evidence that withdrawal of SRIH infusion in man promotes a rebound GH
      response that allegedly has been proposed to be related to the function of GHRH
      producing neurons. In the present study we have evaluated whether a reduction in
      endogenous GHRH activity contributes to the decreased GH secretion of the
      elderly. Sixteen young (8 women, aged 23-32 yr, and 8 men, aged 18-27 yr) and 13
      elderly (8 women, aged 65-82 yr, and 5 men, aged 65-70 yr) healthy subjects
      volunteered to participate in this investigation. Each subject was tested on 2
      separate occasions: 1) a 90-min iv infusion of SRIH was given in 50 mL 0.9%
      saline delivered at a rate of 9 micrograms/kg.h; and 2) a 90-min iv infusion of
      isovolumetric amounts of 0.9% saline was given. Plasma GH levels were determined
      before and up to 180 min after SRIH or saline infusion, whereas plasma insulin
      like growth factor I, estradiol, and testosterone levels were measured in basal
      samples. In elderly women, the mean maximum (delta) GH peak (2 +/- 0.7
      micrograms/L) after withdrawal of SRIH infusion was significantly (P < 0.02)
      lower than that in young women (7.3 +/- 2 micrograms/L). In elderly men, the mean
      delta GH peak (2.9 +/- 0.6 micrograms/L) after withdrawal of SRIH infusion was
      lower than that in young men (6.3 +/- 1.6 micrograms/L), although the difference
      failed to achieve statistical significance. Baseline insulin-like growth factor I
      levels were significantly lower in elderly compared to young subjects in both men
      and in women. In women, both age and basal plasma estradiol and testosterone
      levels significantly correlated with delta GH peak after SRIH withdrawal (r = 
      0.61, r = 0.61, and r = 0.66, respectively), whereas in men they did not. These
      findings are compatible with the view that an age-related decrease in endogenous
      GHRH function may contribute to the defective GH secretion of the elderly.
      Alterations in plasma concentrations of sex steroids may have important
      implications in the observed changes.

PMID- 9284716
TI  - Erratic oscillatory characteristics of plasma insulin concentrations in patients
      with insulinoma: mechanism for unpredictable hypoglycemia.
AB  - Patients with insulin-producing tumors may have hypoglycemic symptoms at
      unpredictable times. This study evaluated whether plasma insulin oscillations,
      known to occur in normal individuals but not explored in patients with
      insulinomas, could be an underlying mechanism for such events. Nine normal
      subjects and five patients with proven insulinomas were studied in the fasting
      state. Serial sampling of arterialized blood over 80-100 min, at 2- or 3-min
      intervals was performed. In normal subjects, mean plasma glucose and insulin
      concentrations were 5.3 +/- 0.1 mmol/L and 58 +/- 9 pmol/L, respectively.
      Regular, low-amplitude plasma insulin oscillations were observed, with a period
      of 10-17 min. The subjects with insulinomas had lower mean plasma glucose and
      higher insulin concentrations than controls, 3.6 +/- 0.3 mmol/L (P = 0.01) and
      150 +/- 42 pmol/L (P = 0.01), respectively. They also had insulin oscillations
      that appeared unstable as a result of variability in duration and amplitude
      compared with controls. The insulin pulses were irregular, and interpeak
      intervals varied between 4-54 min in different subjects; in some subjects, the
      amplitude was also variable, with sudden spontaneous pulses as high as 565
      pmol/L, with an associated glucose decrement. We conclude that large spontaneous
      bursts of insulin secretion occur in patients with insulinomas as part of an
      erratic pattern of oscillatory insulin secretion, and these can account for
      unpredictable occurrences of hypoglycemia.

PMID- 9284717
TI  - Plasma leptin levels in healthy children and adolescents: dependence on body mass
      index, body fat mass, gender, pubertal stage, and testosterone.
AB  - Leptin, the product of the ob gene, is thought to play a key role in the
      regulation of body fat mass. Beyond this function, it appears to be an integral
      component of various hypothalamo-pituitary-endocrine feedback loops. Because
      childhood and puberty are periods of major metabolic and endocrine changes,
      leptin levels and various hormonal parameters were investigated in a large cohort
      of healthy children and adolescents (312 males, 401 females, age 5.8-19.9 yr).
      For this purpose, a specific and sensitive RIA was developed that allowed the
      accurate measurement of low leptin levels in young lean children. With this
      assay, leptin proved to be a comparatively stable protein under common conditions
      of blood sampling and storage. Leptin levels increased in girls with age (r =
      0.47, P < 0.0001), but decreased in boys (r = -0.34, P < 0.0001). An analysis
      according to pubertal stage showed a steady increase in girls between 2.51
      micrograms/L (median) at Tanner stage 1 to 6.24 micrograms/L at Tanner stage 5.
      In boys, leptin levels were highest at Tanner stage 2 (2.19 micrograms/L) and
      declined thereafter to 0.71 microgram/L at Tanner stage 5. A strong exponential
      relationship was observed for leptin levels with body mass index (BMI) and
      percentage body fat as determined by bioelectric impedance measurements in a
      subgroup of subjects. This relationship was similar between boys and girls at
      Tanner stages 1 and 2. In boys, there was a significant decline of leptin at a
      given BMI with further progression of puberty that was much less pronounced in
      girls. Although the relative increase of leptin with BMI and percent body fat was
      the same in both genders, the absolute values at a given BMI or percent body fat
      were significantly lower in boys in late puberty and in adolescents. In boys, but
      not in girls, there was an inverse correlation with testosterone concentrations
      (r = -0.43, P < 0.0001), which explained 10.5% of the variation of leptin levels
      in a multiple regression model. Since BMI proved to be the major influencing
      variable, reference ranges were constructed using a best-fit regression line of
      the form leptin = a*e(b*BMI) and stratifying ranges according to gender and
      pubertal stage. In conclusion, these data suggest that 1) plasma leptin levels
      increase in girls and decrease in boys after Tanner stage 2 as the pubertal
      development proceeds; 2) they show a significant gender difference especially in
      late puberty and adolescence, even after adjustment for BMI or percent body fat;
      3) the lower levels in males may be explained at least in part by a suppressive
      effect of androgens; 4) reference ranges with BMI as the independent variable
      should be stratified according to gender and pubertal stage.

PMID- 9284718
TI  - Dehydroepiandrosterone treatment is not beneficial to the immune response to
      influenza in elderly subjects.
AB  - BACKGROUND: Dehydroepiandrosterone (DHEA) is a native steroid with an
      immunomodulating activity that was suggested to counter-regulate some phenomena
      of immunosenescence. Recently, it was shown to reverse the age-associated decline
      of immune response against influenza vaccine in aged mice. The present study was
      designed to evaluate the effect of DHEA on the immunization of elderly volunteers
      against influenza. METHODS: Seventy-one elderly volunteers age 61-89 yr were
      enrolled in a prospective randomized, double-blind study to receive either DHEA
      (50 mg qd p.o. for four consecutive days starting two days before immunization)
      or placebo. Antibody response to the vaccine was measured before and 28 days
      after vaccination. RESULTS: DHEA treatment significantly increased serum DHEA
      sulfate (DHEA-S). No enhancement in established immunity was observed. A
      significant decrease in attainment of protective antibody titer (1:40 or higher)
      against the A/Texas strain in subjects with nonprotective baseline antibody titer
      was recorded following DHEA treatment compared with placebo (52% vs. 84%, P <
      0.05). Baseline DHEA-S serum levels were inversely related to attainment of
      immunization in DHEA-treated subjects. Influenza-like morbidity during the winter
      was low in the study group with no difference between the DHEA and placebo
      groups. CONCLUSIONS: Although highly effective in aged rodents, a short course of
      DHEA treatment did not improve the age-related declined response to immunization
      against influenza in human subjects. Higher baseline DHEA-S levels are not
      predictive of better immunization against influenza in the elderly.

PMID- 9284719
TI  - Metabolic improvement of poorly controlled noninsulin-dependent diabetes mellitus
      decreases bone turnover.
AB  - Patients with poorly controlled noninsulin dependent diabetes mellitus (NIDDM)
      are shown to have higher bone mass. However, the influence of changes in glycemic
      control on bone turnover is not known. To clarify whether metabolic improvement
      of poorly controlled NIDDM affects bone turnover, markers for glucose, mineral,
      and bone metabolism were assessed before and after glycemic control for 3 weeks
      in 78 poorly controlled NIDDM patients with initial hemoglobin A1c over 8%.
      Metabolic improvement caused a reduction in urinary calcium (Ca) and phosphate
      (Pi) and serum 1,25(OH)2D levels, and an increase in serum Pi without changes in
      serum Ca or parathyroid hormone levels. Bone resorption markers, urinary
      deoxypyridinoline (Dpd) and type I collagen carboxy-terminal telopeptide (CTx),
      as well as a bone formation marker, serum bone type alkaline phosphatase (BALP),
      were reduced. However, another bone formation marker, serum osteocalcin (OC), was
      low before treatment and was elevated after treatment. The decrease in Dpd, CTx
      and BALP, but not the increase in OC, correlated with each other and with the
      improvement in glycemic indices. In conclusion, metabolic improvement of poorly
      controlled NIDDM decreases bone turnover within a short period. Thus, glycemic
      control may protect NIDDM patients from bone loss. It is possible that serum OC
      is affected by hyperglycemia per se, and may not correctly reflect bone turnover.

PMID- 9284720
TI  - Variability of plasma cortisol levels in extremely low birth weight infants.
AB  - Cortisol is secreted by children and adults in a pulsatile pattern of 15-30 peaks
      and nadirs each day with a circadian rhythm. Newborns are known to lack the
      circadian pattern, leading to uncertainty about the appropriate time for blood
      sampling for assessment of adrenal function. Because extremely low birth weight
      (ELBW) infants may manifest signs of adrenal insufficiency, knowledge of the
      pattern of cortisol levels is necessary to guide the appropriate timing of blood
      sampling. To define the pattern of plasma cortisol levels in 14 ELBW infants, we
      obtained blood specimens every 20 min over a 6-h period at 4-6 days of life.
      Although cortisol levels in the 14 infants ranged from 2.0-54.5 micrograms/dL,
      each infant's cortisol levels varied little from his or her own mean cortisol
      level. The SDs calculated from each infant's mean cortisol level were small,
      ranging from 0.37-4.12 micrograms/dL. Cluster analysis was applied to the data;
      only 0.6 cortisol pulses/infant 6-h period were detected. Each infant's plasma
      cortisol levels were plotted against time, and regression analysis was performed.
      The slopes of the resulting lines of regression ranged from -0.0284 to 0.0221.
      Our data indicate that ELBW infants show little variability in their plasma
      cortisol levels over time; therefore, a single random measurement provides an
      adequate reflection of the adrenal status of the ELBW infant.

PMID- 9284722
TI  - Low thyrotropin levels are not associated with bone loss in older women: a
      prospective study.
AB  - The relationship between excess thyroid hormone and bone loss is controversial.
      To determine whether low TSH levels, indicating excessive thyroid hormone, are
      associated with low bone mass or accelerated bone loss in older women, we
      performed a prospective cohort study of 458 women over age 65 yr participating in
      the multicenter Study of Osteoporotic Fractures. Three hundred and twenty-three
      women were randomly selected from the entire cohort of 9704; an additional 135
      randomly selected thyroid hormone users were studied. Medical history, medication
      use, and calcaneal bone mineral density (BMD) were assessed at the baseline
      visit. Serum was collected and stored at -190 C. Hip and spine BMD were measured
      approximately 2 yr later, and follow-up calcaneal and hip BMD measurements were
      obtained after mean follow-up periods of 5.7 and 3.5 yr, respectively. TSH levels
      were determined in baseline serum samples using a third generation
      chemiluminescent assay. After adjustment for age, weight, previous
      hyperthyroidism, and use of estrogen, bone loss over 4-6 yr was similar in women
      with low, normal, or high TSH. For example, femoral neck bone loss was -0.3%/yr
      (95% confidence interval, -0.8%, 0.3%) among women with low TSH (< or = 0.1 mU/L)
      and -0.5%/yr (95% confidence interval, -0.7%, -0.3%) in those with normal TSH
      (0.1-5.5 mU/L). There were no statistically significant differences in baseline
      bone mass of the calcaneus, spine, or femoral neck or trochanteric hip
      subregions. Baseline total hip BMD was 6% lower (P = 0.01) in women with low TSH.
      Similar results were obtained in analyses confined to women not taking estrogens.
      We found no consistent evidence that low TSH, a sensitive biochemical marker of
      excess thyroid hormone, was associated with low BMD or accelerated bone loss in
      older ambulatory women.

PMID- 9284721
TI  - Thyrotropin receptor antibodies and Graves' disease, a side-effect of 131I
      treatment in patients with nontoxic goiter.
AB  - The use of 131I treatment in patients with benign nontoxic goiter is increasing,
      and the described side-effects are few. In this paper we describe appearance of
      TSH receptor antibodies (TRAb) and concomitant development of hyperthyroidism as
      a side-effect of 131I treatment in patients with nontoxic goiter. In this
      retrospective study, 191 consecutive patients with 131I-treated nontoxic goiter
      are described. Nine patients (5%) developed hyperthyroidism 3 months after 131I
      treatment, and 5 patients (3%) developed radiation thyroiditis within the first
      month. Frozen sera were analyzed for thyroid peroxidase antibodies (anti-TPO) in
      130 patients before 131I treatment. In 21% of these, serum levels of anti-TPO
      were over 200 U/mL. The complication frequency of Graves'-like hyperthyroidism
      and hypothyroidism was 51% in patients with elevated anti-TPO (n = 27) and 15% in
      patients with normal serum anti-TPO levels (P < 0.00005). TRAb, anti-TPO, and
      thyroglobulin were followed in patients developing hyperthyroidism or radiation
      thyroiditis and in 10 control patients remaining euthyroid. At the time of 131I
      treatment, all patients had serum TRAb values within the normal range. Three
      months after administration of 131I, the patients developing hyperthyroidism had
      a transient extensive rise in serum TRAb and anti-TPO levels parallel to a rise
      in the serum free T4 index. In patients developing radiation thyroiditis, serum
      TRAb values were normal. In control patients, serum TRAb and anti-TPO values were
      both within the normal range throughout the observation period. In conclusion,
      hyperthyroidism can be triggered by 131I in patients with nontoxic goiter, not
      only related to radiation thyroiditis but also as a Graves'-like hyperthyroidism
      induced by TRAb. Elevated anti-TPO pretreatment is a marker of an increased risk
      of side-effects to 131I treatment in nontoxic goiter.

PMID- 9284723
TI  - Metabolic and cardiovascular assessment in moderate obesity: effect of weight
      loss.
AB  - Metabolic and hemodynamic abnormalities have been separately described in
      obesity, and weight reduction is known to lead to some improvement in each. Our
      aim was to simultaneously assess metabolic and cardiovascular function in
      normotensive, normotolerant patients with moderate obesity (body mass index =
      32.6 +/- 1.1 kg/m2) before and after weight loss. The obese were insulin
      resistant [37.4 +/- 4.8 mumol/min.kg FFM; P < 0.02 vs. 12 lean controls (50.6 +/-
      2.6), on a euglycemic insulin clamp], secreted more insulin both in the fasting
      state and after oral glucose (70 +/- 10 vs. 48 +/- 6 nmol/mmol.L plasma glucose;
      P < 0.05), and had higher resting energy expenditure (4.62 +/- 0.18 vs. 4.00 +/-
      0.23 kJ/min), systolic and mean blood pressure, stroke volume (87 +/- 8 vs. 67 +/
      4 mL/min; P = 0.05), and cardiac output. There was, however, no relationship
      between the metabolic and hemodynamic abnormalities. After a weight loss of 11 +/
      1 kg (approximately 15%), insulin sensitivity improved in proportion to the
      weight reduction, whereas insulin hypersecretion and high energy expenditure
      persisted. In contrast, all hemodynamic changes reverted to normal. We conclude
      that in moderate obesity, the metabolic and cardiovascular abnormalities are
      largely independent of one another; accordingly, weight loss affects them
      differentially. Partial weight normalization may provide sufficient
      cardiovascular protection.

PMID- 9284724
TI  - Increased proportion of circulating non-22-kilodalton growth hormone isoforms in
      short children: a possible mechanism for growth failure.
AB  - Current knowledge about the interaction between GH and its receptor suggests that
      the molecular heterogeneity of circulating GH may have important implications for
      growth. The aim of this study was to investigate the proportion of circulating
      non-22-kDa GH isoforms in prepubertal children with short stature (height less
      than -2 SD score) of different etiologies. We have also evaluated the
      relationships among the ratio of non-22-kDa GH isoforms, auxology, and
      spontaneous GH secretion. The study groups consisted of 17 girls with Turner's
      syndrome (TS), aged 3-13 yr, 25 children born small for gestational age (SGA)
      without postnatal catch-up growth, aged 3-13 yr; and 24 children with idiopathic
      short stature (ISS), aged 4-15 yr. The results were compared with those from 23
      prepubertal healthy children of normal stature (height +/- 2 SD score), aged 4-13
      yr. Serum non-22-kDa GH levels, expressed as a percentage of the total GH
      concentration, were determined by the 22-kDa GH exclusion assay, which is based
      on immunomagnetic extraction of monomeric and dimeric 22-kDa GH from serum and
      quantitation of non-22-kDa GH using a polyclonal antibody-based GH assay. All
      samples were selected from spontaneous GH peaks in 24-h GH profiles. The median
      proportion of non-22-kDa GH isoforms was increased in children born SGA (9.8%; P
      = 0.05) and girls with TS (9.9%; P = 0.01), but not in the group of children with
      ISS (8.9%), compared with that in normal children (8.1%). Individually, increased
      proportions of non-22-kDa GH isoforms, with values more than 2 SD above the mean
      for the normal group, were observed in 5 girls with TS, 5 children born SGA, and
      4 children with ISS. In children born SGA, the proportion of non-22-kDa GH
      isoforms was directly correlated with different estimates of spontaneous GH
      secretion [mean 24-h GH concentration (r = 0.41; P = 0.04), area under the curve
      over baseline (r = 0.41; P = 0.04), and GH peak area (r = 0.61; P = 0.003)],
      whereas it was inversely correlated with height SD score (r = -0.42; P = 0.04).
      In conclusion, an increased proportion of circulating non-22-kDa GH isoforms was
      observed at spontaneous GH peaks in some non-GH-deficient short children. Our
      results suggest that the ratio of non-22-kDa GH isoforms in the circulation may
      have important implications for normal and abnormal growth.

PMID- 9284725
TI  - Comparison of pulsatile luteinizing hormone secretion between prepubertal
      children and young adults: evidence for a mass/amplitude-dependent difference
      without gender or day/night contrasts.
AB  - The assessment of pulsatile GnRH activity in children has become possible since
      the introduction of the sensitive third generation immunochemiluminescent assays,
      permitting detection of previously unmeasurable levels of LH and FSH. Despite
      this, however, studies differ with regard to pulse frequency and the presence of
      a diurnal variation in LH secretion in clinically prepubertal children.
      Discrepancies may reflect the limitations of relatively long intersampling
      intervals, less sensitive LH assays such as RIAs, and the use of algorithms to
      analyze pulsatile LH secretion, which do not account for endogenous production
      rates and metabolic clearance. To address this, we studied LH secretion in 10
      prepubertal children (4 boys and 6 girls, age 8.5-10.8 y) and 12 young adults (7
      men and 5 women in the early follicular phase, age 18.6-32.8 y). Blood was
      sampled every 5 min from 2000 h to 0200 h (nighttime) and from 0800 h to 1400 h
      (daytime) for LH determination, using an immunochemiluminescent assay.
      Deconvolution analysis revealed no difference between daytime and nighttime LH
      secretion, including LH secretory amplitude and pulse frequency, within any of
      the 4 groups, permitting pooling of the data from the 2 sampling intervals for
      analysis. In addition, there was no difference in LH secretion or half-life
      between genders. Comparison of pulsatile LH secretion between children and adults
      revealed a marked increase in the mass and amplitude of LH secreted per burst. LH
      secretory burst mass rose 9.5-fold in females, increasing the mean LH
      concentration by nearly 13-fold and the production rate by nearly 9-fold. The
      trend in males was similar although less remarkable, with a 4.2-fold rise in LH
      secretory burst mass from childhood to adulthood. No differences in pulse
      frequency, interburst interval, half-life, or approximate entropy were found
      between prepubertal children and adults. We conclude that the maturational change
      in LH secretion occurs via a highly specific mass/amplitude-dependent mechanism
      without significant gender or day/night differences.

PMID- 9284726
TI  - Progesterone regulated expression of flavin-containing monooxygenase 5 by the B
      isoform of progesterone receptors: implications for tamoxifen carcinogenicity.
AB  - Progesterone is a key developmental, proliferative, and differentiative hormone
      in the breast and endometrium, and it can accelerate carcinogenesis in the
      mammary gland epithelium. In the breast and uterus, progesterone acts through two
      coexpressed isoforms of progesterone receptors, the B- and A-receptors. To study
      the function of each isoform in isolation, we previously constructed two breast
      cancer cell lines that stably and independently express either B-receptors (YB
      cells) or A-receptors (YA cells). In the present study, YA or YB cells were left
      untreated, or were treated with the synthetic progestin R5020, and the messages
      present in each cell line under the two conditions were analyzed by differential
      display. Two message species are described that are regulated only by B
      receptors. One of these is regulated in a ligand-independent manner. A third set
      of messages, encoding flavin-containing monooxygenase 5 (FMO5), was induced by
      R5020 only in YB cells. A-receptors appear to be inhibitory. FMOs are involved in
      the metabolic activation of drugs and xenobiotic compounds, including the
      antiestrogen tamoxifen, to carcinogenic intermediates. It is possible, therefore,
      that by upregulating the levels of FMO5, progesterone enhances the
      carcinogenicity of tamoxifen in target tissues that overexpress progesterone B
      receptors.

PMID- 9284728
TI  - Association between vitamin D receptor gene polymorphism and sex-dependent growth
      during the first two years of life.
AB  - An association between vitamin D receptor (VDR) gene polymorphisms and bone mass
      variance has been observed in adult populations. To analyze possible association
      between VDR genotype and growth, we studied 589 healthy infants who were
      homogeneous for age, diet, and vitamin D status. The Bsm I, TaqI, and ApaI
      alleles' frequencies and genotypes were similar to those reported for Caucasian
      populations. Variations in Bsm I polymorphism were not associated with calcium
      intakes nor with serum levels of calcium, 25-hydroxyvitamin D, 1, 25
      dihydroxyvitamin D, or alkaline phosphatase activity. But, they were associated
      with differences in body size. At 2 yr, homozygote BB (BsmI site absent) girls
      had higher length, weight and body surface area, and inversely, BB boys had lower
      weight, body mass index and body surface area, than their respective bb
      counterparts. As a result, gender-related differences were observed in Bb and bb,
      but not in BB populations. This VDR genotypic effect was observed also at birth
      and at 10 months in the longitudinal analysis of 145 selected full-term babies
      homozygous for the Bsm I polymorphism. These findings provide support for the
      hypothesis that VDR genotype influences intrauterine and early postnatal growth,
      directly or via interactions with gender-related growth regulators.

PMID- 9284729
TI  - Procollagen propeptide and pyridinium cross-links as markers of type I collagen
      turnover: sex- and age-related changes in healthy children.
AB  - The correlations among age, gender, body size parameters, and type I collagen
      metabolism were evaluated in 183 healthy infants, aged 8.5-27.5 months. Collagen
      formation was assessed by measuring serum type I collagen carboxy-terminal
      propeptide, and degradation was determined by urinary pyridinoline and
      deoxypyridinoline (measured by high performance liquid chromatography) and cross
      linked N- and C-terminal telopeptides of type I collagen (measured by NTx and
      CrossLaps assays). A new RIA specific for deoxypyridinoline was also evaluated.
      The results provide reference values at 10 months and 2 yr of age, including
      cross-linked C-terminal telopeptides (1492 +/- 685 and 1510 +/- 446 in boys; 1705
      +/- 612 and 1849 +/- 611 micrograms/mmol creatinine in girls; mean +/- 1 SD).
      There was a good correlation between the high performance liquid chromatography
      and RIA data for deoxypyridinoline, showing that the RIA method is suitable for
      use in healthy children. Some correlations were found among peptide-bound cross
      links, serum type I collagen carboxy-terminal propeptide, and the anthropometric
      parameters, suggesting that these peptides reflect bone resorption and also
      overall body type I collagen. Finally, there were age- and sex-related
      differences in the urinary excretion of the collagen degradation markers,
      suggesting that, unlike boys, girls maintain a high degree of collagen
      degradation up to the age of 24 months despite a decrease in their rate of
      collagen formation.

PMID- 9284727
TI  - Metastatic prolactinoma: effect of octreotide, cabergoline, carboplatin and
      etoposide; immunocytochemical analysis of proto-oncogene expression.
AB  - A 49-yr-old woman presented with an extensive prolactinoma (serum PRL > 10,000
      mU/L, normal range < 450 mU/L). Over a 5-yr period following transsphenoidal
      surgery and pituitary irradiation, she became increasingly resistant to high
      doses of bromocriptine and underwent transfrontal surgery followed by
      stereotactic radiotherapy. In spite of these treatments, serum prolactin
      estimations rose progressively to > 100,000 mU/L. Magnetic resonance imaging
      scanning demonstrated a massive cystic tumor invading the temporal lobes,
      extending into the cervical and thoracic spine, with metastases to cervical lymph
      nodes. High-dose cabergoline administration resulted in a 30% decrease in serum
      PRL. Octreotide was administered as a continuous sc infusion with a profound
      analgesic effect on facial pain but with no effect on tumor progression. She was
      treated with a course of chemotherapy consisting of carboplatin and etoposide
      without any noticeable effect. The patient died 6 months following chemotherapy.
      Immunocytochemical analysis demonstrated positive nuclear staining for WAF-1, Rb
      protein, c-myc, and p53 both in the original and metastatic tumors. The
      metastases but not the primary tumor stained for c-jun. Metastatic prolactinoma
      remains a therapeutic challenge. It is associated with a variable proto-oncogene
      expression, which may be coincidental or causal. Cabergoline had no advantage
      over bromocriptine. Octreotide relieved facial pain but did not alter tumor
      progression. An effective therapy for metastatic prolactinoma remains to be
      identified.

PMID- 9284730
TI  - Insulin-like growth factor-binding protein-6 levels are elevated in serum of
      children with chronic renal failure: a report of the Southwest Pediatric
      Nephrology Study Group.
AB  - Previous studies suggest that growth retardation in children with chronic renal
      failure (CRF) results in part from inhibition of insulin-like growth factor (IGF)
      action by excess serum IGF-binding proteins (IGFBPs). Excess IGFBPs in CRF serum
      include IGFBP-1, -2, and -3 and a diffuse approximately 24- to 28-kDa IGFBP band
      identified by [125I]IGF ligand blot. The present studies characterized this
      diffuse approximately 24- to 28-kDa band. Initial studies identified this band as
      IGFBP-6, because it was immunoprecipitated by antiserum raised against a
      synthetic peptide of human IGFBP-6 (hIGFBP-6). Additional [125I]IGF ligand blots
      found that the immunoprecipitated band was 1) recognized by [125I]IGF-II but not
      [125I]IGF-1, 2) more abundant in CRF than in normal serum, and 3) more abundant
      in serum from dialyzed than nondialyzed prepubertal CRF children. Using the
      hIGFBP-6 antiserum in a specific and sensitive RIA, we found that serum IGFBP-6
      levels were 4.7 +/- 1.7 nmol/L in 10 normal prepubertal children, 21.4 +/- 6.1
      nmol/L in 44 nondialyzed prepubertal CRF children, 73.5 +/- 14.4 nmol/L in 7
      dialyzed prepubertal CRF children, and 94.6 +/- 26.2 nmol/L in 14 dialyzed
      pubertal CRF children. IGFBP-6 levels were also elevated in 71 nondialyzed
      European children with CRF. In nondialyzed CRF children, serum IGFBP-6 levels 1)
      correlated inversely with the glomerular filtration rate, 2) did not correlate
      with height SD score, and 3) were not altered by 12 months of daily recombinant
      hGH treatment. In summary, a specific antiserum and RIA were used to demonstrate
      elevated levels of intact IGF-II-binding IGFBP-6 in serum of CRF children. We
      postulate that the excess IGFBP-6 may modulate the action of IGF-II on target
      tissues.

PMID- 9284732
TI  - Changes of dimeric inhibin B levels in maternal serum throughout healthy
      gestation and in women with gestational diseases.
AB  - Human placenta expresses subunit messenger RNAs for synthesizing inhibin A and B.
      Experimental studies have shown an effect of inhibins on placental hormone
      secretion, but an endocrine function is suggested by the high levels in maternal
      circulation. Although information is available on the changes of inhibin A in
      serum of healthy pregnant women, data on inhibin B levels are limited to early
      gestation. The aim of the present study was to investigate the changes of inhibin
      B levels in maternal circulation in healthy pregnant women throughout gestation,
      and to evaluate whether early pregnancy disturbances or gestational diseases are
      characterized by abnormal inhibin B levels. The protocol included various groups
      of pregnant women. A longitudinal evaluation of serum inhibin B levels was done
      at specific intervals (8-12, 13-18, 19-24, 25-28, 29-33, and 34-40 weeks) in the
      following groups: 1) healthy pregnant women (n = 13); 2) women at risk of
      hypertension who did not develop hypertension (n = 8); and 3) women with chronic
      hypertension (n = 13). In women in group 1, a blood sample was also obtained in
      the postpartum period (12, 24, and 48 h after delivery). Other pregnant women
      with abnormal bleeding in the first trimester were studied; they were subdivided
      into women with ongoing pregnancy (n = 12); and women with miscarriage (n = 22);
      a control group of healthy pregnant women at the same gestational age was also
      included (n = 18). A final group of women with gestational diseases (n = 34) was
      included in the study and included women with: 1) pregnancy-induced hypertension
      (n = 10); 2) preeclampsia (n = 17); and 3) intrauterine fetal growth retardation
      (n = 7). A group of healthy nonpregnant women (n = 9) was used as controls, and a
      blood specimen was collected during both the early- to midfollicular and
      midluteal phases of the menstrual cycle. Serum dimeric inhibin B levels were
      measured by using a double-antibody enzyme-linked immunoadsorbent assay. Early
      gestation inhibin B levels were similar to those of nonpregnant controls and
      showed a significant rise during the third trimester (P < 0.01). The highest
      maternal serum inhibin B levels were found at term (P < 0.01). Values
      significantly returned to control levels within 12-48 h (P < 0.01) after
      placental delivery. Women at risk of hypertension showed a similar gestational
      related increase of inhibin B levels during the third trimester, without any
      significant difference when compared with healthy women. Women with chronic
      hypertension showed significantly lower levels at term (P < 0.01). Women with
      pregnancy-induced hypertension or preeclampsia, or who were carrying a fetus with
      intrauterine growth retardation showed serum inhibin B levels during the third
      trimester of gestation consistently lower than in control healthy women at the
      same gestational age (P < 0.001, mean +/- SEM). Maternal serum inhibin B levels
      in women with early pregnancy bleeding or miscarriage were similar to those of
      healthy pregnant women at the same gestational age, independent from the outcome
      of gestation. The present study showed that maternal serum inhibin B levels
      increase in the last trimester of normal pregnancy, with low levels in women with
      hypertensive disturbances or intrauterine growth retardation.

PMID- 9284731
TI  - The importance of growth hormone in the regulation of erythropoiesis, red cell
      mass, and plasma volume in adults with growth hormone deficiency.
AB  - Total body water (TBW) is reduced in adult GH deficiency (GHD) largely due to a
      reduction of extracellular water. It is unknown whether total blood volume (TBV)
      contributes to the reduced extracellular water in GHD. GH and insulin-like growth
      factor I (IGF-I) have been demonstrated to stimulate erythropoiesis in vitro, in
      animal models, and in growing children. Whether GH has a regulatory effect on red
      cell mass (RCM) in adults is not known. We analyzed body composition by
      bioelectrical impedance and used standard radionuclide dilution methods to
      measure RCM and plasma volume (PV) along with measuring full blood count,
      ferritin, vitamin B12, red cell folate, IGF-I, IGF-binding protein-3, and
      erythropoietin in 13 adult patients with GHD as part of a 3-month, double blind,
      placebo-controlled trial of GH (0.036 U/kg.day). TBW and lean body mass
      significantly increased by 2.5 +/- 0.53 kg (mean +/- SEM; P < 0.004) and 3.4 +/-
      0.73 kg (P < 0.004), respectively, and fat mass significantly decreased by 2.4 +/
      0.32 kg (P < 0.001) in the GH-treated group. The baseline RCM of all patients
      with GHD was lower than the predicted normal values (1635 +/- 108 vs. 1850 +/-
      104 mL; P < 0.002). GH significantly increased RCM, PV, and TBV by 183 +/- 43 (P
      < 0.006), 350 +/- 117 (P < 0.03), and 515 +/- 109 (P < 0.004) mL, respectively.
      The red cell count increased by 0.36 +/- 0.116 x 10(12)/L (P < 0.03) with a
      decrease in ferritin levels by 39.1 +/- 4.84 micrograms/L (P < 0.001) after GH
      treatment. Serum IGF-I and IGF-binding protein-3 concentrations increased by 3.0
      +/- 0.43 (P < 0.001) and 1.3 +/- 0.15 (P < 0.001) SD, respectively, but the
      erythropoietin concentration was unchanged after GH treatment. No significant
      changes in body composition or blood volume were recorded in the placebo group.
      Significant positive correlations could be established between changes in TBW and
      TBV, lean body mass and TBV (r = 0.78; P < 0.04 and r = 0.77; P < 0.04,
      respectively), and a significant negative correlation existed between changes in
      fat mass and changes in TBV in the GH-treated group (r = -0.95; P < 0.02). We
      conclude that 1) erythropoiesis is impaired in GHD; 2) GH stimulates
      erythropoiesis in adult GHD; and 3) GH increases PV and TBV, which may contribute
      to the increased exercise performance seen in these patients.

PMID- 9284733
TI  - Effect of aging on the sensitivity of growth hormone secretion to insulin-like
      growth factor-I negative feedback.
AB  - To determine the effect of aging on the suppression of GH secretion by insulin
      like growth factor (IGF)-I, we studied 11 healthy young adults (6 men, 5 women,
      mean +/- SD: 25.2 +/- 4.6 yr old; body mass index 23.7 +/- 1.8 kg/m2) and 11
      older adults (6 men, 5 women, 69.5 +/- 5.8 yr old; body mass index 24.2 +/- 2.5
      kg/m2). Saline (control) or recombinant human IGF-I (rhIGF-I) (2 h baseline then,
      in sequence, 2.5 h each of 1, 3, and 10 micrograms/kg.h) was infused iv during
      the last 9.5 h of a 40.5-h fast; serum glucose was clamped within 15% of
      baseline. Baseline serum GH concentrations (mean +/- SE: 3.3 +/- 0.7 vs. 1.9 +/-
      0.5 micrograms/L, P = 0.02) and total IGF-I concentrations (219 +/- 15 vs. 103 +/
      19 micrograms/L, P < 0.01) were higher in the younger subjects. In both age
      groups, GH concentrations were significantly decreased by 3 and 10
      micrograms/kg.h, but not by 1 microgram/kg.h rhIGF-I. The absolute decrease in GH
      concentrations was greater in young than in older subjects during the 3 and 10
      micrograms/kg.h rhIGF-I infusion periods, but both young and older subjects
      suppressed to a similar GH level during the last hour of the rhIGF-I infusion
      (0.78 +/- 0.24 microgram/L and 0.61 +/- 0.16 microgram/L, respectively). The
      older subjects had a greater increase above baseline in serum concentrations of
      both total (306 +/- 24 vs. 244 +/- 14 micrograms/L, P = 0.04) and free IGF-I (8.5
      +/- 1.4 vs. 4.2 +/- 0.6 micrograms/L, P = 0.01) than the young subjects during
      rhIGF-I infusion, and their GH suppression expressed in relation to increases in
      both total and free serum IGF-I concentrations was significantly less than in the
      young subjects. We conclude that the ability of exogenous rhIGF-I to suppress
      serum GH concentrations declines with increasing age. This suggests that
      increased sensitivity to endogenous IGF-I negative feedback is not a cause of the
      decline in GH secretion that occurs with aging.

PMID- 9284734
TI  - Endogenous glucose production following injury increases with age.
AB  - To evaluate the influence of aging on the increase in endogenous glucose
      production that follows injury, we studied 22 fully resuscitated, clinically
      stable, previously healthy patients aged < or = 30 yr or > or = 60 yr admitted to
      hospital following injury, and 11 healthy volunteers in the same age groups.
      Endogenous glucose production was determined using a primed constant infusion of
      D-glucose-6,6-2d2. Urine cortisol and C-peptide were markedly higher in patients
      than volunteers (both P < 0.01), and urine C-peptide was lower in older than in
      younger patients (P < 0.05). Urine cortisol increased as a function of the
      interaction of age and Injury Severity Score (ISS) (r2 = 0.40, P < 0.001).
      Intracellular water was markedly lower and extracellular water greater in
      patients compared with volunteers (both P < 0.001), reflecting the loss of body
      cell mass and expansion of the extracellular space following injury. Endogenous
      glucose production (milligrams per minute per liter intracellular water) was best
      described as a function of ISS and age-ISS interaction (r2 = 0.35, all P < 0.05),
      and was increased 56% and 78% in younger and older patients, respectively, in
      comparison with the respective volunteer groups. Endogenous glucose production
      following injury increases in relation to the severity of injury and patient age.
      Greater cortisol elaboration and diminished insulin secretion in older patients
      may contribute to this age effect.

PMID- 9284735
TI  - Dissociation between the effects of somatostatin (SS) and octapeptide SS-analogs
      on hormone release in a small subgroup of pituitary- and islet cell tumors.
AB  - The effects of somatostatin (SS-14 and/or SS-28) and of the three octapeptide SS
      analogs that are available for clinical use (octreotide, BIM-23014 and RC-160) on
      hormone release by primary cultures of 15 clinically nonfunctioning pituitary
      adenomas (NFA), 7 prolactinomas, and 2 insulinomas were investigated. In the
      pituitary adenoma cultures, a comparison was made with the effects of the
      dopamine (DA) agonists bromocriptine and/or quinagolide. In 5 NFAs, 2
      prolactinomas and 1 insulinoma somatostatin receptor (subtype) expression was
      determined by ligand binding studies and by in situ hybridization to detect sst1,
      sst2, and sst3 messenger RNAs (mRNAs). Four NFA cultures did not secrete
      detectable amounts of alpha-subunit, FSH, and/or LH. In the other cultures,
      hormone and/or subunit release was inhibited by DA-agonists (10 nM) in 9 of 11,
      by SS (10 nM) in 7 of 11, and by octapeptide SS-analogs (10 nM) in 3 of 10
      cultures. In three NFA cultures, hormone release was sensitive to SS but not to
      SS-analogs. In all cultures, except for one, DA-agonists were the most effective
      in inhibiting hormone release. In the prolactinoma cultures, PRL release was
      inhibited by DA-agonists (10 nM) in 7 of 7, by SS in 4 of 4, and by octapeptide
      SS-analogs in 3 of 7 cultures. A dissociation between the effects of SS and SS
      analogs was found in 3 cases. In the cultures sensitive to both bromocriptine and
      SS-28, bromocriptine was the most potent compound in 2 out of 4 cultures. In the
      2 other cultures, both compounds were equally effective. In 2 insulinoma
      cultures, insulin release was inhibited by SS, and by octapeptide SS-analogs in
      only one. The presence or absence of an inhibitory effect by octreotide was in
      all cases in parallel with the presence or absence of the inhibitory effect by
      BIM-23014 and RC-160. Autoradiographic studies using [125I-Tyr0]SS28 showed
      specific binding in 4 of 5 NFAs, 1 of 2 prolactinomas, and 1 of 1 insulinoma.
      Specific [125I-Tyr3]octreotide binding was found in 2 of 5 NFAs, in 1 of 2
      prolactinomas, and in the insulinoma. Two NFAs showed binding of SS28, but not of
      the sst2.5 specific ligand octreotide. The tumors showed variable sst1 and/or
      sst3 mRNA expression, whereas no sst2 expression was found. In conclusion, a
      dissociation between the inhibitory effects of SS on the one hand and of the
      octapeptide SS-analogs octreotide, BIM-23014 and RC-160 on the other hand, is
      observed in a small subgroup of NFAs, prolactinomas, and insulinomas, suggesting
      that novel sst subtype specific SS-analogs might be of benefit in the treatment
      of selected patients with somatostatin receptor positive secreting tumors not
      responding to octapeptide SS-analogs. However, in the majority of NFAs and
      prolactinomas, DA-agonists were equally or more effective than SS in the
      suppression of tumoral secretion products.

PMID- 9284736
TI  - Evidence for the oligoclonal origin of the granulosa cell population of the
      mature human follicle.
AB  - The clonality of the granulosa cell population residing in individual mature
      human ovarian follicles was examined by determining the pattern of X chromosome
      inactivation. Granulosa cells from 72 follicles were obtained from 9 patients
      undergoing oocyte harvest for in vitro fertilization. The granulosa cell DNA
      obtained from each follicle was subjected to the PCR, to amplify a highly
      polymorphic region of the X-linked human androgen receptor gene, after digestion
      by the methylation-sensitive HpaII restriction endonuclease, thereby achieving
      exclusive amplification of the inactive allele. Seventeen of 65 informative
      follicles (26 +/- 5%) were comprised of granulosa cells exhibiting inactivation
      of the same X chromosome. At least 1 such follicle was found in 8 of the 9 women
      sampled. There are 2 possible explanations for these findings: 1) approximately
      one fourth of all follicles contain a truly monoclonal granulosa cell population;
      2) the granulosa cells of a given follicle are derived from a small number of
      stem cells (3 cells), such that the probability is 0.25 that all 3 stem cells
      producing the granulosa cell complement of a given follicle have the same X
      chromosome inactivated by chance. We favor the latter explanation and conclude
      that the granulosa cell cohort of mature human follicles is oligoclonal.

PMID- 9284740
TI  - Specific linkages among luteinizing hormone, follicle-stimulating hormone, and
      testosterone release in the peripheral blood and human spermatic vein: evidence
      for both positive (feed-forward) and negative (feedback) within-axis regulation.
AB  - We have investigated possible (negative) feedback and (positive) feed-forward
      activity within the human male gonadotropic axis by measuring serum
      concentrations of LH, FSH, and testosterone in blood sampled frequently and for a
      prolonged interval (every 20 min for 19 h) simultaneously from the peripheral
      circulation and the left spermatic vein. Cross-correlation analysis with time lag
      was used to evaluate relationships among serial serum LH, FSH, and/or
      testosterone concentrations over time (i.e. consistency or dissociation of trends
      in concentrations). Separately, Cluster analysis was applied to identify discrete
      LH, FSH, and testosterone pulses, which were cataloged for possible peak
      coincidence. The hypergeometric probability distribution was then used to test
      the null hypothesis that LH, FSH, and testosterone pulses are randomly
      associated. Cross-correlation analysis revealed: 1) peripheral blood LH and
      testosterone concentrations correlate positively at lags of 40-120 min with LH
      increases preceding testosterone increases, viz., feed-forward (P < 0.001); 2) LH
      and FSH concentrations in peripheral blood are positively correlated in
      simultaneous blood samples, as well as when FSH lags LH by 20 min (P < 0.01); 3)
      unexpectedly, LH and FSH concentrations in peripheral blood are inversely related
      at a lag of 80-100 min (P = 0.002) and 0.004, respectively) where LH lags FSH; 4)
      LH and testosterone concentrations in the spermatic vein show strongly positive
      correlations at lags of 80, 100, and 120 min (P = 0.002, 0.004, and 0.021,
      respectively); 5) spermatic vein testosterone concentrations correlate negatively
      with peripheral blood LH concentrations 20 or 40 min later (P = 0.012 and 0.05,
      respectively), which indicates autonegative feedback; and 6) in contrast,
      testosterone levels in the spermatic vein correlate negatively with FSH values in
      the periphery 100 and 120 min later (P < 0.01), indicating more delayed negative
      feedback of testosterone on serum FSH concentrations. Discrete pulse coincidence
      analysis disclosed: 1) a total of 30 testosterone pulses in the spermatic vein
      and 25 testosterone pulses in peripheral blood, with 28 LH and 29 FSH pulses in
      the periphery; 2) individual LH and FSH peak concordance was significantly
      nonrandom for FSH pulse maxima lagging LH pulse maxima by 20 min (P < 0.05 vs.
      randomness), with 6 observed coincidences vs. 2.9 +/- 1.5 (SD) expected; 3)
      peripheral LH pulses and spermatic vein testosterone pulses were strongly
      nonrandomly coupled at an 80-min lag, with 8 events observed vs. 3.0 +/- 1.5
      events expected (P = 0.004); and 4) LH peaks in peripheral blood followed
      testosterone peaks in the spermatic vein by 40 min in a nonrandom manner,
      specifically, n = 11 observed vs. 3.0 +/- 1.5 expected (P < 0.001), indicating
      possible LH escape from testosterone's negative feedback. In summary,
      physiological regulation of the human male LH, FSH, and testosterone axis
      comprises multidirectional interactions, consisting of both (positive) feed
      forward and (negative) feedback coupling. Based on a concept of network
      integration, we propose that age and other pathophysiological factors might
      modulate and/or disrupt these dynamic within-axis multihormonal linkages.

PMID- 9284738
TI  - The hypothalamic-pituitary-adrenocortical axis in severe falciparum malaria:
      effects of cytokines.
AB  - Patients with malaria can have features of adrenal insufficiency. Because of the
      pathophysiological and clinical implications of an Addisonian state, the
      hypothalamic-pituitary-adrenocortical axis was assessed in nine Vietnamese adults
      with complicated malaria. A CRH test was performed on admission (in convalescence
      in five cases) and in six healthy controls. Basal plasma ACTH concentrations in
      the patients and controls were similar [median (range): 2.9 (0.2-9.7) vs. 3.5
      (1.9-13.4) pmol/L, respectively; P > 0.1]. Serum cortisol levels were greater in
      the patients [882 (294-1682) vs. 190 (110-676) nmol/L; P < 0.01], but three (33%)
      had values within the control range. Basal serum corticosteroid-binding globulin
      concentrations were similar in patients and controls (P = 0.23). The post-CRH
      rise in plasma ACTH was attenuated in the patients [peak: 6.1 (0.9-23.2) vs. 14.5
      (6.2-21.5) pmol/L in controls; P < 0.05]; basal and peak plasma ACTH correlated
      with plasma interleukin-6 in this group (rs > or = 0.60; P < or = 0.04). Serum
      cortisol responses to CRH were depressed in acute illness [peak 990 (394-1, 805)
      nmol/L or 10 (0-50%) above baseline vs. 500 (429-703) nmol/L or 160 (10-380%) in
      controls; P < 0.05]. The median estimated serum cortisol t1/2 was 4.6 h in the
      patients and 1.6 h in the controls. These data suggest that, relative to a normal
      stress response, primary and secondary adrenal insufficiency can occur in severe
      malaria but may be attenuated by increased circulating interleukin-6
      concentrations and impaired cortisol metabolism. The benefits of stress-dose
      corticosteroid replacement are unknown but could be considered in hypoglycemic
      patients or those with a serum cortisol within or below the reference range.

PMID- 9284739
TI  - Short-term variations in bone remodeling biochemical markers: cyclical etidronate
      and alendronate effects compared.
AB  - Bone-remodeling markers have been proposed to monitor antiosteoporotic therapy,
      as substantial changes in these markers usually occur in a relatively short time
      interval. In this study we have evaluated the short term effects of two
      bisphosphonates on bone-remodeling markers with the aim of 1) defining the
      shortest reliable time interval after which markers should be measured, and 2)
      comparing the effects of different bisphophonates. To do so, 74 postmenopausal
      women with a lumbar spine t score of at least -1 were randomly allocated to 4
      different treatments: calcium carbonate (500 mg/day; n = 18), 5 mg/day
      alendronate (A5; n = 18), 10 mg/day alendronate (A10; n = 20), and cyclical
      etidronate (CE; n = 18). Serum and 24-h urine samples were collected at baseline
      and 14, 28, 56, and 84 days after the beginning of therapy. Type I collagen N
      terminal (NTx) and C-terminal (CTx) telopeptides and total deoxypyridinoline
      (tDPD) were measured in urine and normalized for urinary creatinine excretion.
      Osteocalcin and bone alkaline phosphatase in serum were measured. Alendronate (at
      both doses) and CE significantly decreased bone-remodeling markers, whereas
      calcium carbonate did not. Bone resorption markers reduction reached a plateau 14
      (A10) or 28 (A5 and CE) days after the beginning of treatment, whereas
      osteocalcin and bone alkaline phosphatase were significantly reduced at 56 (A10)
      and 84 (CE) days. The global effects of alendronate and CE on NTx and CTx
      (calculated as the area under the curve) were significantly different from those
      of calcium (P < 0.05), but were not significantly different from each other. The
      percent change from baseline obtained with tDPD, NTx, or CTx during
      bisphosphonate treatment were significantly different (P < 0.05), but this
      difference disappeared when the variability in the calcium carbonate group was
      taken into account. In conclusion, this study shows that 1) etidronate and
      alendronate induce a significant and rapid reduction in bone-remodeling markers;
      2) the changes in NTx, CTx, and tDPD urinary excretions reach a plateau after 2-4
      wk of treatment; and 3) short term treatments with CE or alendronate induce
      similar changes in the urinary excretion of NTx and CTx.

PMID- 9284737
TI  - Mutation analysis of glial cell line-derived neurotrophic factor, a ligand for an
      RET/coreceptor complex, in multiple endocrine neoplasia type 2 and sporadic
      neuroendocrine tumors.
AB  - Causative germline missense mutations in the RET proto-oncogene have been
      associated with over 92% of families with the inherited cancer syndrome multiple
      endocrine neoplasia type 2 (MEN 2). MEN 2A is characterized primarily by
      medullary thyroid carcinoma (MTC) and pheochromocytoma, both tumors of neural
      crest origin. Parathyroid hyperplasia or adenoma is also seen in MEN 2A, but
      rarely in MEN 2B, which has additional stigmata, including a marfanoid habitus,
      mucosal neuromas, and ganglioneuromatosis of the gastrointestinal tract. In
      familial MTC, MTC is the only lesion present. Somatic RET mutations have also
      been identified in a subset of sporadic MTCs, pheochromocytomas, and rarely,
      small cell lung cancer, but not in sporadic parathyroid hyperplasias/adenomas or
      other neuroendocrine tumors. Glial cell line-derived neurotrophic factor (GDNF)
      and its receptor molecule GDNFR-alpha, have recently been identified as members
      of the RET ligand binding complex. Therefore, the genes encoding both GDNF and
      GDNFR-alpha are excellent candidates for a role in the pathogenesis of those MEN
      2 families and sporadic neuroendocrine tumors without RET mutations. No mutations
      were found in the coding region of GDNF in DNA samples from 9 RET mutation
      negative MEN 2 individuals (comprising 6 distinct families), 12 sporadic MTCs, 17
      sporadic cases of parathyroid adenoma, and 10 small cell lung cancer cell lines.
      Therefore, we find no evidence that mutation within the coding regions of GDNF
      plays a role in the genesis of MEN 2 and sporadic neuroendocrine tumors.

PMID- 9284741
TI  - Complementary deoxyribonucleic acid cloning and characterization of a putative
      human axonemal dynein light chain gene.
AB  - Immotile Cilia Syndrome (ICS) is characterized by recurrent sinus and lung
      infections, bronchiectasis, and sperm immotility. Nasal cilia and sperm tails in
      patients with ICS exhibit a variety of ultrastructural defects, often including
      shortening or absence of the inner dynein arms. Immotile mutant strains of
      Chlamydomonas, a biflagellated algae, have ultrastructural defects similar to
      those seen in patients with this clinical disorder. Furthermore, splice-site
      mutations in the Chlamydomonas inner dynein arm gene (p28) are associated with
      impaired flagellar motility. We therefore hypothesized that the human homologue
      of the Clamydomonas dynein p28 gene would be an attractive candidate gene for
      patients with ICS. Accordingly, we cloned the full length complementary DNA
      (cDNA) and genomic clone by screening of appropriate libraries and databases,
      using the protein sequence of the Chlamydomonas p28 gene. The human homologue is
      encoded by a 921 bp transcript (accession no. AF006386) with an open reading
      frame of 257 amino acids. Using somatic cell and radiation hybrid panels, the
      hp28 gene was mapped to human chromosome 1p35.1. The hp28 cDNA probe hybridizes
      to sequences in all species on a zoo blot containing genomic DNA from yeast to
      human. Northern blot analysis reveals two hp28 gene transcripts, 0.9 and 2.5 kb,
      in many tissues. The 0.9 kb transcript is expressed at a 20-fold higher level
      than the 2.5-kb transcript in the testis. The entire gene is included in a 20-kb
      EcoRI genomic fragment and has 7 exons and 6 introns. Cloning of the hp28 cDNA
      and mapping of the intron-exon junctions should now make it possible to test
      whether a subset of ICS is a consequence of mutations in the human axonemal
      dynein light chain gene hp28.

PMID- 9284742
TI  - Deletion of the adrenocorticotropin receptor gene in human adrenocortical tumors:
      implications for tumorigenesis.
AB  - Constitutive activating mutations of G protein-coupled receptors, such as that of
      TSH, have been implicated in the tumorigenesis of human endocrine neoplasms, such
      as thyroid adenomas. In a previous study we reported that constitutive activating
      point mutations of the ACTH receptor (ACTH-R) gene, a member of the G protein
      coupled receptor superfamily, were not present in hormone-secreting and
      nonsecretory adrenocortical neoplasms. In this study, we investigated whether
      allelic loss of the ACTH-R gene is present in sporadic adrenal tumors. We
      identified a PstI polymorphism in the promoter region 3 kilobases upstream of the
      coding region of the ACTH-R gene. The rate of heterozygosity for this
      polymorphism in 99 unrelated Caucasian individuals was 53.5%. Using this
      polymorphism, we analyzed loss of heterozygosity (LOH) of the ACTH-R gene in 20
      informative cases with benign and malignant adrenocortical tumors. Of 16 patients
      with benign lesions, LOH was present in 1 oncocytic nonfunctional adenoma, but
      not in 15 hyperfunctioning adenomas. Of 4 informative patients with
      adrenocortical carcinomas, LOH was present in 2 cases. Both patients had advanced
      tumor stages and showed a more rapid course than carcinoma patients without LOH.
      Analysis of the flanking region of the ACTH-R using the polymorphic microsatelite
      marker D18S37 and D18S40 showed that this deletion was confined to the ACTH-R
      gene. Northern blot experiments demonstrated reduced expression of ACTH-R
      messenger ribonucleic acid in the tumors with LOH of the ACTH-R gene, suggesting
      functional significance of this finding at the transcriptional level. We conclude
      that LOH of the ACTH-R gene is possibly involved in adrenal tumorigenesis,
      contributing to cellular dedifferentiation in adenomas and carcinomas.

PMID- 9284744
TI  - Identification of a large-scale mitochondrial deoxyribonucleic acid deletion in
      endocrinopathies and deafness: report of two unrelated cases with diabetes
      mellitus and adrenal insufficiency, respectively.
AB  - In recent years, a broad variety of chronic diseases have been related to
      different mitochondrial DNA (mtDNA) rearrangements. We have investigated two 16
      yr-old unrelated girls with unexplained endocrine disorders for a mtDNA mutation.
      One initially presented with an adrenal crisis at the age of 4 yr. Complete
      adrenal insufficiency for nearly 15 yr was the main clinical manifestation, along
      with insiduous growth retardation and sensorineural hearing loss since age 6. The
      other girl presented with ketoacidosis at the age of 15 yr. She exhibited
      incomplete deafness since age 6 and poor growth. In both patients, brain magnetic
      resonance imaging abnormalities and raised cerebrospinal fluid protein
      concentration indicated mild leucodystrophy. Biopsy of skeletal muscle showed a
      mitochondrial dysfunction; molecular analysis using a PCR screening procedure
      revealed a 7.4 kb deletion of the mtDNA in skeletal muscle but not in leucocytes.
      Direct sequence analysis of the junctional regions showed that the deletion
      spanned 7.436 kb (nucleotide 8649 to nucleotide 16084). The relative amount of
      deleted mtDNA estimated by Southern blot analysis was 25 and 15%, respectively.
      No deletion was present in leukocytes obtained from the asymptomatic mothers. The
      presence of the same mutation in different patients with various endocrine
      conditions supports the view that the 7.4 kb mtDNA deletion should be considered
      as one of the candidate causes for phenotypically uncommon cases of
      endocrinopathies, specially in children with deafness. This is the first report
      of a mitochondrial disease with primary adrenocortical insufficiency as the
      clinical onset.

PMID- 9284743
TI  - The expression and activity of prostaglandin H synthase-2 is enhanced in
      trophoblast from women with preeclampsia.
AB  - Preeclampsia is associated with altered biosynthesis of vasoactive prostanoids in
      placental villi. The two isozymes of prostaglandin H synthase (PGHS) are
      essential for prostanoid synthesis. We tested the hypothesis that PGHS-2
      expression is elevated in trophoblast from preeclamptic women, compared with
      trophoblast from healthy women. Using immunofluorescent staining, we demonstrated
      a higher PGHS-2 expression in villi from preeclampsia, compared with normal
      pregnancy. Cytotrophoblasts cultured from placentas of preeclamptic women
      expressed higher levels of PGHS-2 compared with cytotrophoblasts from normal
      placentas. This enhanced expression of PGHS-2 correlated with increased media
      levels of both thromboxane and prostaglandin E2, two products of PGHS activity.
      The increased prostanoid production by trophoblast from preeclamptic women was
      markedly reduced by NS-398, a specific inhibitor of PGHS-2. We conclude that both
      expression and activity of PGHS-2 are enhanced in trophoblasts from preeclamptic
      women compared with trophoblast from normal pregnancies. The increased production
      of prostanoids may contribute to the clinical syndrome of preeclampsia. Our data
      suggest that a selective inhibitor of PGHS-2 might provide a therapeutic
      alternative to prophylactic low-dose aspirin in modifying the prostanoid profile
      in preeclampsia.

PMID- 9284747
TI  - Simulation of human luteal endocrine function with granulosa lutein cell culture.
AB  - Human granulosa cells collected from in vitro fertilization have previously been
      cultured to provide a system to simulate the granulosa lutein cells of the corpus
      luteum. In most of these systems, the cultures have been relatively short term,
      and attempts to simulate the normal pattern of hormone production observed during
      the luteal phase of the cycle have not been reported. Additionally, the hormone
      relaxin has generally been absent from the endocrine analysis of these systems.
      In this report, methods were used that supported secretion of ovarian steroids
      and relaxin that mimics the profiles of these hormones in vivo. This system was
      used to observe the endocrine responses of the granulosa lutein cells to three
      different protocols of CG administration designed to mimic the normal luteal
      phase, early pregnancy, and early pregnancy followed by pregnancy loss. The
      normal luteal phase was simulated by a constant baseline (0.02 IU/mL) CG model to
      simulate a nonconceptive cycle (baseline). The second model was baseline CG until
      day 8 of culture, followed by daily doubling from days 9-17 to simulate an early
      pregnancy (rescue-plateau). CG concentrations were then held constant from days
      17-20 (5.12 IU/mL). A third model (rescue-drop) was used that was identical to
      the early pregnancy model except that on day 17 CG was returned to baseline
      concentrations (0.02 IU/mL) to simulate an early pregnancy loss. Baseline CG
      stimulation resulted in profiles of estrogen, progesterone, and relaxin secretion
      in culture that were closely related to secretory profiles previously reported in
      serum during the nonconceptive luteal phase. The timing of appearance of relaxin
      secretion and later declines in steroid and relaxin secretion paralleled that
      observed in serum. In the CG rescue protocols, ovarian steroids rose in response
      to daily doubling of CG and fell when CG either plateaued or fell. Relaxin did
      not show an increase in response to increasing CG, but its secretion did not drop
      when CG concentrations plateaued or dropped. This cell culture system model
      mimics the profile of ovarian steroids and relaxin seen in serum during the
      nonconceptive luteal phase, although the relative magnitude of the hormones was
      not the same as seen in vivo. It was also used to investigate responses to luteal
      rescue protocols designed to simulate early pregnancy and pregnancy loss. This
      culture system may be useful to study differences in endocrine response in
      granulosa cells collected from different patients and to provide information of
      clinical relevance. This culture system provides a model to study luteal function
      and its response to different protocols of luteal rescue and thus may provide
      insight into early pregnancy and pregnancy loss.

PMID- 9284745
TI  - Renal clearance of the thyrotropin-releasing hormone-like peptide pyroglutamyl
      glutamyl-prolineamide in humans.
AB  - TRH-like peptides have been identified that differ from TRH (pGlu-His-ProNH2) in
      the middle amino acid. We have estimated TRH-like immunoreactivity (TRH-LI) in
      human serum and urine by RIA with TRH-specific antiserum 8880 or with antiserum
      4319, which binds most peptides with the structure pGlu-X-ProNH2. TRH was
      undetectable in serum (< 25 pg/mL), but TRH-LI was detected with antiserum 4319
      in serum of 27 normal subjects, 21 control patients, and 12 patients with
      carcinoid tumors (range 17-45, 5-79, and 18-16,600 pg/mL, respectively). Because
      serum was kept for at least 2 h at room temperature, which causes degradation of
      TRH, pGlu-Phe-ProNH2, and pGlu-Tyr-ProNH2, serum TRH-LI is not caused by these
      peptides. On high-performance liquid chromatography, serum TRH-LI coeluted with
      pGlu-Glu-ProNH2 (< EEP-NH2), a peptide produced in, among others, the prostate.
      Urine of normals and control patients also contained TRH-LI (range 1.14-4.97 and
      0.24-5.51 ng/mL, respectively), with similar levels in males and females. TRH
      represented only 2% of urinary TRH-LI, and anion-exchange chromatography and high
      performance liquid chromatography revealed that most TRH-LI in urine was < EEP
      NH2. In patients with carcinoid tumors, increased urinary TRH-LI levels were
      noted (range 1.35-962.4 ng/mL). Urinary TRH-LI correlated positively with urinary
      creatinine, and the urinary clearance rate of TRH-LI was similar to the
      glomerular filtration rate. In addition, serum TRH-LI was increased in 17
      hemodialysis patients (43-373 pg/mL). This suggests that serum < EEP-NH2 is
      cleared by glomerular filtration with little tubular resorption. The possible
      role of the prostate as a source of urinary TRH-LI was evaluated in 11 men with
      prostate cancer, showing a 25% decrease in urinary TRH-LI excretion after
      prostatectomy (0.19 +/- 0.02 vs. 0.15 +/- 0.01 ng/mumol creatinine, mean +/-
      SEM). However, TRH-LI was similar in spontaneously voided urine and in urine
      obtained through a nephrostomy cannula from 16 patients with unilateral urinary
      tract obstruction (0.15 +/- 0.01 vs. 0.14 +/- 0.01 ng/mumol creatinine). These
      data indicate that: 1) TRH-LI in human serum represents largely < EEP-NH2, which
      is cleared by renal excretion; 2) part of urinary < EEP-NH2 is derived from
      prostatic secretion into the blood and not directly into urine; and 3) urinary <
      EEP-NH2 can be used as marker for carcinoid tumors.

PMID- 9284748
TI  - Interleukin 1 alpha increases serum leptin concentrations in humans.
AB  - Leptin, the protein product of the ob gene, regulates appetite and body weight in
      animals. Endotoxin and cytokines, induced by endotoxin, interleukin (IL) 1 and
      tumor necrosis factor, increase expression of leptin in mice and hamsters. We
      measured serum leptin concentrations in patients with cancer before and after
      administration of recombinant human IL-1 alpha. Fourteen patients received IL-1
      alpha at one of three dose levels (0.03, 0.1, or 0.3 microgram/kg.day) for 5
      days. Serum leptin concentrations increased in all but two patients within 24 h
      after the first dose. The increase in leptin was correlated directly with IL-1
      alpha dose (P = 0.0030). Despite continued administration of IL-1 alpha, serum
      leptin concentrations returned to pretreatment levels by day 5 of therapy. An
      increase in serum leptin concentrations may be one mechanism by which anorexia is
      induced by IL-1 alpha. However, tachyphylaxis of the leptin response suggests
      that other mechanisms also are involved.

PMID- 9284746
TI  - The effect of a desogestrel-containing oral contraceptive on glucose tolerance
      and leptin concentrations in hyperandrogenic women.
AB  - Ovarian hyperandrogenism can be associated with insulin resistance,
      hyperinsulinemia, glucose intolerance, and obesity. High levels of the lipostatic
      hormone, leptin, have also been reported in this condition. The purpose of the
      present study was to examine the effect of an oral contraceptive (OC) of low
      androgenicity containing desogestrel on glucose tolerance in hyperandrogenic
      women and the impact of changes in androgenic/estrogenic status on leptin
      concentrations. Sixteen nondiabetic hyperandrogenic women, aged 29 +/- 1 yr with
      a body mass index (BMI) of 36.8 +/- 1.8 kg/m2, underwent an oral glucose
      tolerance test before and after 6 months of therapy with the OC. Free
      testosterone decreased and sex hormone-binding globulin increased after therapy
      (P < 0.001). Glucose tolerance deteriorated significantly, and two women
      developed diabetes. Body weight, BMI, and leptin did not change significantly.
      Leptin correlated with BMI before (r = 0.56; P = 0.02) and after (r = 0.51; P =
      0.04) treatment, but not with glucose, insulin, total and free testosterone, or
      sex hormone-binding globulin before or after treatment. In conclusion, 1) glucose
      tolerance should be monitored in hyperandrogenic women using OC, even those of
      low androgenicity; and 2) changes in androgenic/estrogenic status had no effect
      on the leptin concentration, suggesting that its sexual dimorphism is not related
      to sex steroids.

PMID- 9284749
TI  - Activation of adenylyl cyclase in human myometrial smooth muscle cells by
      neuropeptides.
AB  - The levels of intracellular cAMP in human myometrial smooth muscle cells in serum
      free medium, or medium that contained FBS (1%, vol/vol), were determined after
      treatment with the homologous peptides, calcitonin gene-related peptide (CGRP),
      adrenomedullin (ADM), and amylin, without or with added isobutylmethylxanthine
      (IBMX). These cells were sensitive to CGRP, responding in a dose-dependent
      manner, with maximal levels of cAMP being attained with 5 nM CGRP in the presence
      of IBMX (1 mM). In the absence of IBMX, the level of cAMP attained in cells
      treated with CGRP (5 nM) (675.3 +/- 58.8 pmol.mg protein.15 min; mean +/- SEM, n
      = 3) was approximately 90x that in nontreated cells (7.5 +/- 0.4 pmol.mg
      protein.15 min). The level of cAMP in myometrial cells treated with CGRP (5
      nM)+IBMX (1 mM), 1998 +/- 420 pmol.mg protein.15 min, was 29x that in cells
      treated with IBMX alone (69.2 +/- 10.2). The maximum level of cAMP achieved by
      treatment with ADM+IBMX was similar to that with CGRP+IBMX, but the dose of ADM
      required (1 microM) was approximately 200x that of CGRP. Amylin amide also caused
      an increase in cAMP but with considerably less potency; at a concentration of 500
      nM, amylin amide+IBMX effected a 2.3-fold increase in cAMP relative to IBMX
      alone. CGRP8-37, an antagonist of CGRP via the CGRP1 receptor, inhibited the
      action of CGRP, ADM, and amylin in myometrial cells. Treatment with [cys(ACM)2-7]
      CGRP, a CGRP2 receptor agonist, did not cause an increase in the levels of cAMP
      in these cells. These findings are indicative that CGRP, ADM, and amylin act via
      that the CGRP1 receptor in human myometrial cells. Vasoactive intestinal peptide
      and pituitary adenylate cyclase activating polypetide also caused a dose
      dependent increase in cAMP in myometrial cells. The findings of this study are
      indicative that multiple neuropeptides, acting by way of heptahelical receptors
      linked to the G alpha s-subunit of the G-proteins, may contribute to the
      maintenance of uterine quiescence during some period of human pregnancy.

PMID- 9284750
TI  - Pituitary adenylate cyclase-activating polypeptide stimulates insulin and
      glucagon secretion in humans.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) has been localized to
      pancreatic nerves and demonstrated to stimulate insulin and glucagon secretion in
      experimental animals. This study examined the occurrence and possible function of
      PACAP in the human pancreas. The content of PACAP27 was 0.44 +/- 0.04 pmol/g
      tissue, and that of PACAP38 was 29.6 +/- 6.4 pmol/g tissue in extracted human
      pancreas (n = 4). Furthermore, in a homogeneous group of seven healthy
      postmenopausal women, all aged 57 yr, iv infusion of synthetic human PACAP27 (3
      pmol/kg.min for 75 min) increased basal levels of insulin, C peptide, and
      glucagon without significantly influencing basal glucose after 14 min. At 15 min,
      glucose was administered rapidly (0.3 g/kg, iv). The peak insulin after bolus
      glucose was 797 +/- 232 pmol/L during PACAP27 infusion vs. 559 +/- 164 pmol/L
      during saline infusion (P = 0.018). Also, the peak in C peptide after glucose was
      potentiated by PACAP27 (P = 0.018). In contrast, hepatic extraction, calculated
      as the C peptide/insulin molar ratio, was not significantly affected by PACAP27,
      and neither the glucose elimination rate nor reduction of serum insulin after the
      glucose-induced peak was changed by PACAP27. We conclude that PACAP occurs in
      human pancreas and stimulates insulin and glucagon secretion in humans. This
      suggests that PACAP is involved in the regulation of islet function in humans.

PMID- 9284751
TI  - Methimazole and propylthiouracil equally cross the perfused human term placental
      lobule.
AB  - Propylthiouracil (PTU) is widely believed to cross the placenta less freely than
      methimazole (MMI) and is therefore regarded as the preferred drug for treatment
      of hyperthyroidism in pregnancy. Clinical studies comparing the two drugs show,
      however, no differences in maternal or fetal thyroid function. We investigated
      transfer from the maternal to the fetal circuit in the isolated perfused term
      human placental lobule of low and high doses of PTU (4 micrograms/mL and 40
      micrograms/mL) and MMI (1.5 micrograms/mL and 15 micrograms/mL) in protein-free
      perfusate and low doses of both drugs with addition of 40 g/L of bovine albumin.
      Both drugs readily crossed the placenta, reaching equilibrium in all experiments
      in about 2 h. Drug concentrations in the two circuits fitted a two compartmental
      model. Transfer kinetics for the two drugs were similar, nonsaturable, and
      unaffected by addition of albumin. Clearances (mL.min-1.g-1, means +/- SD) of PTU
      from maternal to fetal circuits were: 0.229 +/- 0.110, 0.216 +/- 0.065, and 0.170
      +/- 0.032; and for transfer of MMI: 0.165 +/- 0.025, 0.232 +/- 0.153, and 0.174
      +/- 0.009 (for low doses without, low doses with, and high doses without albumin,
      respectively). Clearances of PTU from fetal to maternal circuits were: 0.147 +/-
      0.072, 0.109 +/- 0.014, and 0.116 +/- 0.028; and for transfer of MMI: 0.095 +/-
      0.029, 0.122 +/- 0.088, and 0.12 +/- 0.005 (in the same experiments). There was
      no significant difference between drugs or drug doses and no effect of addition
      of albumin. We conclude that PTU and MMI have similar placental transfer
      kinetics.

PMID- 9284752
TI  - Changes in the isoforms of luteinizing hormone and follicle-stimulating hormone
      during puberty in normal children.
AB  - Concentrations of LH and FSH are known to increase during normal pubertal
      development, but changes in the isoforms of the gonadotropins at this time have
      not been investigated in depth. We examined the median charge of serum LH and FSH
      using agarose suspension electrophoresis in 81 normal children at pubertal stages
      I-V. In pubertal girls there were no significant (P > 0.05) differences in the
      median charge of LH, but there was a small (P = 0.05) shift to more acidic FSH
      isoforms between pubertal stages I and IV. In boys there was a significant (P <
      0.01) shift to more acidic isoforms for both LH and FSH by pubertal stage II.
      Further changes were not found later in puberty. Except for LH at pubertal stage
      I, where the median charge was similar (P > 0.05) for both sexes, the median
      charge was more basic (P < 0.001) for both LH and FSH in girls compared with boys
      at all five pubertal stages. The degree of charge heterogeneity of FSH, estimated
      as the peak width at half the peak height, was significantly (P < 0.01) larger at
      pubertal stage I than at pubertal stages III-V in both boys and girls. The charge
      heterogeneity of LH was similar for all pubertal stages in both sexes. In
      conclusion, there were few qualitative changes in the gonadotropins during normal
      female puberty, whereas in the male there was a dramatic shift to more acidic
      isoforms of LH and FSH early in puberty. This information may assist our
      understanding of normal and pathological processes during puberty and may be of
      clinical relevance in detecting the initiation of puberty in boys.

PMID- 9284753
TI  - Anti-prolactin (PRL) autoantibodies cause asymptomatic hyperprolactinemia:
      bioassay and clearance studies of PRL-immunoglobulin G complex.
AB  - The causes of hyperprolactinemia are varied, but some cases are classified as
      "idiopathic" because of unknown causes. We examined whether anti-prolactin (PRL)
      autoantibodies can cause hyperprolactinemia, especially the asymptomatic type.
      Serum PRL in four women with anti-PRL autoantibodies and five control patients
      with prolactinoma was characterized by a sensitive enzyme immunoassay, Nb2
      bioassay, gel chromatography, affinity chromatography for immunoglobulin G (IgG),
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under
      nonreducing conditions, and clearance studies using anesthetized rats. In four
      women with anti-PRL autoantibodies, serum immunoreactive PRL concentrations were
      elevated (326 +/- 216 micrograms/L, normal < 30 micrograms/L), and PRL (84 +/-
      5.5%) mostly consisted of the large molecular form in which a significant amount
      of 23 kDa PRL (60.6 +/- 14.7%) was noncovalently bound to IgG. Although three of
      the four women lacked clinical symptoms of hyperprolactinemia such as amenorrhea
      and galactorrhea, the IgG-bound PRL was fully bioactive in vitro. It was cleared
      more slowly from circulation than free PRL. The data suggest that PRL forms a
      complex with IgG, and this probably results in delayed clearance of PRL and leads
      to hyperprolactinemia in women with anti-PRL autoantibodies.

PMID- 9284754
TI  - Effects of chemotherapy-induced testicular damage on inhibin, gonadotropin, and
      testosterone secretion: a prospective longitudinal study.
AB  - To investigate the role of inhibin in the control of follicle-stimulating hormone
      (FSH) secretion, we have measured levels of immunoreactive inhibin (ir-inhibin),
      inhibin B, Pro-alpha C containing inhibins, FSH, luteinizing hormone (LH), and
      testosterone in twelve men with hematological malignancies before, during, and
      after chemotherapy. Inhibin B levels fell significantly by 1 month from a mean +/
      SE baseline level of 273.2 +/- 32.8 pg/mL, reaching a nadir of 52.6 +/- 15.3
      pg/mL at 4 months (P < 0.0001). FSH levels increased within the first month from
      a baseline level of 3.9 +/- 0.6 IU/L, reaching a peak level of 22.4 +/- 3.3 IU/L
      at 4 months (P < 0.0001). FSH and inhibin B were significantly and inversely
      correlated (r = 0.69, P < 0.0001). Pro-alpha C containing inhibin levels
      increased significantly (P < 0.05) at 3 months and were significantly and
      positively correlated with FSH (r = 0.38, P = 0.002). LH levels increased
      significantly but to a much lesser extent than FSH, the increase becoming evident
      only 4 months after treatment commenced (P < 0.03). Levels of ir-inhibin and
      testosterone remained unchanged throughout the study. These data provide strong
      support to the hypothesis that inhibin B is the physiologically important form of
      inhibin in men, negatively regulating FSH secretion at the pituitary.
      Furthermore, they suggest that FSH stimulates inhibin alpha-subunit secretion by
      the testis.

PMID- 9284755
TI  - Endothelin-1 and ETA receptor expression in vascular smooth muscle cells from
      human placenta: a new ETA receptor messenger ribonucleic acid is generated by
      alternative splicing of exon 3.
AB  - Endothelin-1 (ET-1) is a potent vasoactive peptide in stem villi vessels, which
      are considered to be the major sites of placental vascular resistance. To
      investigate the influence of pregnancy-specific hormonal environment on ET and ET
      receptor (ET-R) expression, we first developed and characterized a culture of
      vascular smooth muscle cells from stem villi vessels. Secondly, we investigated
      whether the muscular layer of stem villi vessels could be a site of the ET
      expression described in the placenta, and we examined this expression in
      placental vascular smooth muscle cells (PVSMCs). Prepro-ET-1 and prepro-ET-3
      messenger ribonucleic acid (mRNA) were identified in stem villi vessels, whereas
      only prepro-ET-1 mRNA was observed in PVSMCs. Third, with the goal of using
      PVSMCs as ET target cells, we characterized the ET-R expressed by these cells in
      comparison with the muscular layer of stem villi vessels. Whereas both ETA-R and
      ETB-R are present in stem villi vessels, we found that PVSMCs express exclusively
      ETA-R. In addition to the previously reported ETA-R spliced transcripts, we
      described a new ETA-R transcript, ETA-R delta 3, generated by exclusion of exon 3
      in stem villi vessels and PVSMCs. Alternative splicing mechanisms of ETA-R mRNA
      could constitute a control of the abundance of active ETA-R in terms of
      contractility. PVSMCs will be a useful model to study the environmental stimuli
      involved in the regulation of ET and ET-R expression in the muscular layer of
      feto-placental vasculature.

PMID- 9284757
TI  - The death of osteocytes via apoptosis accompanies estrogen withdrawal in human
      bone.
AB  - Estrogen withdrawal in women leads initially to rapid bone loss caused by
      increased numbers or activity of osteoclasts. We previously have noted apoptosis
      of lacunar osteocytes associated with conditions of high bone turnover.
      Therefore, in this study, we investigated whether the increased bone loss
      associated with GnRH analogue (GnRH-a)-induced estrogen withdrawal affects
      osteocyte viability in situ in a way that would be directly contrary to the
      effect of estrogens on osteoclast viability. Transiliac biopsies were obtained
      from six premenopausal women, between 30-45 yr old, diagnosed as having
      endometriosis. Biopsies were taken before and after 24 weeks of GnRH-a therapy.
      Biopsies were snap-frozen and cryostat sectioned. Osteocyte viability, determined
      by the presence of lactate dehydrogenase (LDH) activity, was reduced in all but
      one subject after treatment. Furthermore, in every subject, the proportion of
      osteocytes showing evidence of DNA fragmentation typical of apoptosis increased,
      as demonstrated using in situ DNA nick translation (P = 0.008). Gel
      electrophoresis of extracted DNA and morphological studies of chromatin
      condensation and nuclear fragmentation confirmed that changes typical of
      apoptosis were affecting the osteocytes. It was concluded that GnRH-a therapy
      caused a higher prevalence of dead osteocytes in iliac bone, probably caused by
      the increase in the observed proportion of osteocytes showing apoptotic changes.
      The capacity of bone to repair microdamage and to modulate the effects of
      mechanical strain is currently believed to be dependent on osteocyte viability.
      Our findings have therefore revealed a possible mechanism whereby estrogen
      deficiency could lead to increased bone fragility with or without an accompanying
      net bone loss.

PMID- 9284756
TI  - The effect of oral glucose on serum free insulin-like growth factor-I and -II in
      health adults.
AB  - Insulin-like growth factor (IGF) binding protein-I (IGFBP-1) has been suggested
      to regulate the availability of free IGF and the glucose lowering activity of the
      IGF-system in relation to fuel supply. Our recent observations of significant
      inverse correlations between free IGF-I and IGFBP-1 in cross-sectionally
      collected fasting serum samples support a possible physiological association
      between the peptides. To further study the impact of IGFBP-1 on free IGF levels
      and the possible participation of the IGF-system in glucose homeostasis, we
      studied the time course of changes in IGFBP-1 and free IGFs in 13 healthy
      subjects undergoing an oral glucose tolerance test (OGTT). Serum was collected
      every 30 min for 330 min. Glucose, insulin, and GH followed the expected patterns
      and had regained baseline levels at 270 min. Total IGF-I and free and total IGF
      II remained unaltered. IGFBP-1 decreased significantly by 37-52% (P < 0.05) from
      150 to 210 min, whereafter the concentration gradually increased by 75% to a
      level that tended to be above baseline (P = 0.052). Free IGF-I decreased by 29
      38% (P < 0.05) at the end of the study (270-330 min). IGFBP-1 was inversely
      correlated to free IGF-I at baseline (r = -0.57; P < 0.05), as well as during the
      OGTT (r = 0.66; P < 0.0001). In contrast, free IGF-II was not correlated to IGFBP
      1. Insulin, but not free IGF-I, correlated significantly with serum glucose (P <
      0.05). These results extend our previous findings of an inverse correlation
      between free IGF-I and IGFBP-1 in cross-sectional studies to include longitudinal
      observations, and thus further substantiates the hypothesis that IGFBP-1 is an
      important determinant of free IGF-I in vivo. Significant changes in free IGF-I
      were observed only in the late postprandial phase, when glucose and insulin were
      fully normalized, demonstrating that free IGFs probably do not participate in
      glucoregulation to any significant degree during an oral glucose load in healthy
      subjects.

PMID- 9284758
TI  - Relevance of major histocompatibility complex class II expression as a hallmark
      for the cellular differentiation in the human adrenal cortex.
AB  - Major histocompatibility complex (MHC) class II antigens are expressed on
      adrenocortical cells of the zona reticularis and have been shown to be a marker
      of dignity. This suggests a correlation to the zellular differentiation of the
      adrenal cortex. Therefore, we immunohistochemically investigated the MHC class II
      expression in the context of the ontogenesis of the zonal and cellular
      differentiation in fetal, postnatal, childhood, and adult adrenals. Cell types
      and cell turnover were studied using specific immune markers (including
      expression of CD95/ Fas), in situ end labeling of apoptosis, and electron
      microscopy. We show that prenatal (fetal and definitive) steroid cells, as well
      as postnatal adrenals, reveal no expression of MHC class II. In childhood, these
      antigens first appear by the fourth year, in parallel with the differentiation of
      reticularis cells. The expression index in childhood was 7.43% +/- 2.78 (mean +/-
      SEM), in adult adrenals 18.63% +/- 3.14 (third decade), and 15.15% +/- 1.26
      (fourth through sixth decade). In conclusion, MHC class II expression and the
      development of the functional maturation of the adult adrenal cortex occur
      simultaneously. The expression of MHC class II on steroid cells may thus be
      involved in potential immune-adrenal interactions.

PMID- 9284759
TI  - Infrequent mutations of p27Kip1 gene and trisomy 12 in a subset of human
      pituitary adenomas.
AB  - To study the etiologic roles of genes on chromosome 12 for the pituitary
      tumorigenesis of adenomas, mutations of the p27Kip1 gene and allelic ratios of 18
      microsatellite markers on the entire chromosome 12 were studied in 33 pituitary
      adenomas. The p27Kip1 gene on chromosome 12p12-p13 encoding an inhibitor of
      complexes between cyclins and cyclin-dependent kinases is supposed to function as
      the tumor suppressor gene. Among 31 sporadic and 2 familial pituitary adenomas,
      PCR-single strand conformation polymorphism analysis detected three polymorphic
      changes but no tumor-specific mutations of the p27Kip1 gene. Genotyping of 18
      microsatellite markers on the entire chromosome 12 detected the uniformly
      decreased allelic ratios ranging from 54-66% in 8 of 33 pituitary adenomas (24%),
      although no loss of heterozygosity was detected. Fluorescence in situ
      hybridization confirmed trisomy 12 in all 5 available samples out of these 8
      samples. Based on these, we conclude that not mutations of the p27Kip1 gene, but
      trisomy 12 may be etiologically important in a subgroup of pituitary adenomas.

PMID- 9284760
TI  - Programmed cell death in human ovary is a function of follicle and corpus luteum
      status.
AB  - Although extensive investigation on follicular apoptosis (programmed cell death)
      has been conducted in the infraprimate ovary, there is little information
      regarding apoptosis and its relationship to follicular status in the human. In
      this study, apoptosis was investigated in 116 human ovarian follicles (primordial
      to dominant) and 5 corpora lutea from a total of 27 premenopausal women.
      Follicles and corpora lutea were evaluated for the presence of DNA fragmentation,
      characteristic of apoptosis, by two methods: in situ hybridization using 3' end
      labeling of DNA with digoxigenin-labeled nucleotides and subsequent digoxigenin
      antibody and peroxidase staining, and/or biochemical analysis of low molecular
      weight DNA laddering. Follicle functional status was evaluated by determining
      follicle sizes and follicular fluid androgen/estrogen (A/E) ratios. No apoptosis
      was observed in 67 primordial, primary, or secondary follicles. Positive staining
      for DNA fragmentation was found in a few granulosa cells in 0.1- to 2-mm
      follicles, whereas abundant staining in granulosa was detected in 2.1- to 9.9-mm
      follicles. In contrast, no DNA fragmentation was detected in dominant follicles
      (10-16 mm). The frequency of apoptosis in follicles was calculated to be 37% in
      0.1- to 2-mm follicles, 50% in 2.1- to 5-mm follicles, and 27% in 5.1- to 9.9-mm
      follicles. Abundant low molecular weight DNA laddering was only found in androgen
      dominant follicles and not in estrogen-dominant follicles. Positive staining for
      DNA fragmentation and low molecular weight DNA laddering were observed in
      degenerating but not healthy-appearing corpora lutea. In the former, DNA
      fragmentation was found primarily in large luteal cells. These data suggest that
      follicular atresia in human ovary results from normal programmed cell death and
      primarily occurs in the granulosa cell layers of the early antral and < 10-mm
      antral follicles primarily. Furthermore, because apoptosis occurs as early as the
      200-mm stage, follicle selection may begin as early as the initial formation of
      the antrum. The results also suggest that degeneration of the corpus luteum
      occurs by apoptotic mechanisms.

PMID- 9284761
TI  - Mutations in the vitamin D receptor gene in three kindreds associated with
      hereditary vitamin D resistant rickets.
AB  - Hereditary vitamin D resistant rickets has been associated with a number of
      mutations within the DNA and ligand binding domains of vitamin D receptors (VDR).
      The aim of our study was to identify and characterize the causative mutations in
      three kindreds with this condition. Resistance of 1,25(OH)2D3 was confirmed in
      cultured skin fibroblasts in which there was no induction of 24-hydroxylase
      activity; binding of 1,25(OH)2D3 to VDR was undetectable in patients 1 and 2, but
      normal in patients 3 and 4. The coding region of the VDR gene was sequenced to
      seek mutations. A mutation in the VDR gene of patient 1 resulted in a STOP codon,
      patient 2 showed a 56 bp deletion leading to frameshift and premature termination
      of VDR; a point mutation of A to C lying within the hormone-binding domain was
      shown for patients 3 and 4, who were siblings. Transactivation studies confirmed
      that these were functional mutations. Gel shift assays using nuclear extract from
      patient 3 demonstrated that the mutation that altered a conserved amino acid
      (glutamine-259) known to be involved in heterodimerization with other nuclear
      receptors affected protein: protein interactions.

PMID- 9284762
TI  - Glucocorticoids do not regulate the expression of proteolytic genes in skeletal
      muscle from Cushing's syndrome patients.
AB  - Glucocorticoids signal enhanced proteolysis in various instances of muscle
      atrophy and increased gene expression of components of the lysosomal, Ca(2+)
      dependent, and/or ubiquitin-proteasome proteolytic pathways in both rat skeletal
      muscle and myotubes. Cushing's syndrome is characterized by chronic excessive
      glucocorticoid production, which results in muscle wasting. We report here no
      change in messenger RNA levels for cathepsin D (a lysosomal proteinase), m
      calpain (a Ca(2+)-activated proteinase), ubiquitin, 14-kDa ubiquitin-activating
      enzyme E2, and 20S proteasome subunits (i.e. critical components of the ubiquitin
      proteasome proteolytic process) in skeletal muscle from such patients. Thus, in
      striking contrast with animal studies, glucocorticoids did not regulate the
      expression of muscle proteolytic genes in Cushing's syndrome. In humans,
      messenger RNA levels, for at least ubiquitin and proteasome subunits, are
      elevated in acute situations of muscle wasting, such as head trauma or sepsis.
      Because Cushing's syndrome is a chronic catabolic condition, we suggest that the
      lack of regulation of proteolytic genes in such patients may represent an
      adaptive regulatory mechanisms, preventing sustained increased protein breakdown
      and avoiding rapid muscle wasting.

PMID- 9284763
TI  - Acute pharmacological reduction of plasma free fatty acids enhances the growth
      hormone (GH)-releasing hormone-mediated GH secretion in patients with Cushing's
      syndrome.
AB  - In Cushing's syndrome, GH secretion is blocked with all the stimuli tested. It
      has been reported that the acute pharmacological reduction of free fatty acids
      (FFA) leads to an enhancement of GH secretion in normal subjects and in
      pathological conditions associated with reduced GH secretion. To understand if
      the elevated FFA levels of hypercortisolism may be responsible for the altered GH
      secretion, 14 patients with active Cushing's syndrome underwent 2 paired tests
      with 100 micrograms i.v. of GHRH on 2 different occasions. In one test, they were
      pretreated with placebo and in the other one, with acipimox 250 mg p.o. 4 h
      before, and 250 mg p.o. 1 h before GHRH. The basal FFA levels (799 +/- 57 mmol/L)
      were reduced by acipimox throughout the whole test (values under 240 +/- 28
      mmol/L). In the placebo pretreated group, GHRH-induced GH secretion was severely
      impeded, with a mean GH peak of 1.8 +/- 0.3 micrograms/L and area under the curve
      of 121.3 +/- 21.6 micrograms/L-120 min. All the patients showed a GHRH-mediated
      GH peak under 4 micrograms/L. Acute reduction of FFA by acipimox enhanced the
      GHRH action, with a mean GH peak of 11.1 +/- 1.8 micrograms/L and area under the
      curve of 652.9 +/- 110.3 micrograms/L-120 min (both P < 0.005). Individually
      analyzed after acipimox, all 14 subjects presented an enhancement in the GHRH
      mediated GH peak, and 8 patients showed a response over 10 micrograms/L. In
      conclusion, acute FFA reduction by acipimox increased the GH secretion elicited
      by GHRH in chronic hypercortisolism. Elevated FFA may be a contributing factor to
      the deranged GH secretion observed in Cushing's syndrome.

PMID- 9284764
TI  - Identification of pro-EPIL and EPIL peptides translated from insulin-like 4
      (INSL4) mRNA in human placenta.
AB  - Recently, a new member of the insulin gene superfamily termed insulin-like 4
      (INSL4) was identified in the human placenta and uterus. The present study
      investigated whether placenta translates INSL4 mRNA into a putative peptide named
      early placenta insulin-like (EPIL). Among antibodies elicited against the C chain
      of pro-EPIL, one antibody (AB7381) was specifically directed against the C chain
      59-88 portion, and among those elicited against the A and B chains of EPIL, one
      antibody (Ab1661) was directed against the A chain 115-139 and the B chain 23-52
      portions. Immunohistochemistry based on antibody 7381 to pro-EPIL and antibody
      1661 to EPIL demonstrated that the cytotrophoblast from early placenta
      preferentially expresses the pro-EPIL peptide, whereas the EPIL peptide is
      expressed by both the cytotrophoblast and the syncytiotrophoblast. At term, the
      pro-EPIL peptide was detected in villous cytotrophoblast cells, whereas the EPIL
      peptide was not detected. Moreover, in vitro experiments performed on term
      placenta showed that the steady state levels of INLS-4 mRNA in the
      cytotrophoblast are 10 times (one log unit) lower than in the differentiated
      villous syncytiotrophoblast cells. Taken together, these findings reveal that
      expression of EPIL peptides in the villous cytotrophoblast is different from that
      displayed by the syncytiotrophoblast. Finally, these data are the first
      demonstration that INSL4 mRNA are translated into pro-EPIL and EPIL peptides.

PMID- 9284765
TI  - Expression of the apoptosis-inducing Fas ligand (FasL) in human first and third
      trimester placenta and choriocarcinoma cells.
AB  - The Fas (Apo-1/CD95) ligand (FasL) belongs to the tumor necrosis factor family
      and acts through its receptor (FasR/ Apo-1/CD95) to induce apoptosis in target
      cells. FasL is expressed in several immunologically privileged sites. Induction
      of apoptosis by FasL in invading lymphocytes acts as a mechanism of immune
      privilege and is important in preventing graft rejection. Furthermore, FasL is
      expressed in certain malignancies and it has been implicated as a possible key
      mechanism in immune privilege of these tumors. Since the invading placental
      trophoblast is another very important site with a privileged immune status, we
      investigated whether FasL is expressed in the normal and tumoral human placenta.
      For this purpose, mRNA was extracted from first and third trimester human
      placental samples as well as from JEG3 choriocarcinoma cells and reverse
      transcribed to obtain cDNAs. These were used as templates for PCR analysis of
      FasL expression, in which specific primers were employed to amplify an 853 bp
      fragment spanning the whole FasL coding region. A product of the appropriate
      length was amplified from normal placenta as well as from the choriocarcinoma
      cells. Expression of FasL protein was confirmed by Western Blot and was localized
      to trophoblast by immunohistochemistry using a FasL-specific antibody. Expression
      of FasL in the human placenta indicates that induction of apoptosis in
      lymphocytes by the invading trophoblast could be an important mechanism
      implicated in the immune tolerance of the fetal semi-allograft.

PMID- 9284766
TI  - Another use of androgens: treatment of anemia of end-stage renal disease.

PMID- 9284767
TI  - The effect of acute administration of ACTH and levothyroxine on serum carnitine.

PMID- 9284768
TI  - Selling out.

PMID- 9284769
TI  - Tackling bacterial vaginosis and HIV in developing countries.

PMID- 9284770
TI  - No rush to obliterate genital tract colonisation in pregnant women.

PMID- 9284771
TI  - Radical surgery or radiotherapy for stage Ib-IIa cervical cancer.

PMID- 9284772
TI  - Stenting for acute myocardial infarction.

PMID- 9284773
TI  - Glutamine supplementation in artificial nutritional support.

PMID- 9284774
TI  - Randomised study of radical surgery versus radiotherapy for stage Ib-IIa cervical
      cancer.
AB  - BACKGROUND: Stage Ib and IIa cervical carcinoma can be cured by radical surgery
      or radiotherapy. These two procedures are equally effective, but differ in
      associated morbidity and type of complications. In this prospective randomised
      trial of radiotherapy versus surgery, our aim was to assess the 5-year survival
      and the rate and pattern of complications and recurrences associated with each
      treatment. METHODS: Between September, 1986, and December, 1991, 469 women with
      newly diagnosed stage Ib and IIa cervical carcinoma were referred to our
      institute. 343 eligible patients were randomised: 172 to surgery and 171 to
      radical radiotherapy. Adjuvant radiotherapy was delivered after surgery for women
      with surgical stage pT2b or greater, less than 3 mm of safe cervical stroma, cut
      through, or positive nodes. The primary outcome measures were 5-year survival and
      the rate of complications. The analysis of survival and recurrence was by
      intention to treat and analysis of complications was by treatment delivered.
      FINDINGS: 170 patients in the surgery group and 167 in the radiotherapy group
      were included in the intention-to-treat analysis; scheduled treatment was
      delivered to 169 and 158 women, respectively, 62 of 114 women with cervical
      diameters of 4 cm or smaller and 46 of 55 with diameters larger than 4 cm
      received adjuvant therapy. After a median follow-up of 87 (range 57-120) months,
      5-year overall and disease-free survival were identical in the surgery and
      radiotherapy groups (83% and 74%, respectively, for both groups), 86 women
      developed recurrent disease: 42 (25%) in the surgery group and 44 (26%) in the
      radiotherapy group. Significant factors for survival in univariate and
      multivariate analyses were: cervical diameter, positive lymphangiography, and
      adeno-carcinomatous histotype. 48 (28%) surgery-group patients had severe
      morbidity compared with 19 (12%) radiotherapy-group patients (p = 0.0004).
      INTERPRETATION: There is no treatment of choice for early-stage cervical
      carcinoma in terms of overall or disease-free survival. The combination of
      surgery and radiotherapy has the worst morbidity, especially urological
      complications. The optimum therapy for each patient should take account of
      clinical factors such as menopausal status, age, medical illness, histological
      type, and cervical diameter to yield the best cure with minimum complications.

PMID- 9284775
TI  - Submissiveness and protection from coronary heart disease in the general
      population: Edinburgh Artery Study.
AB  - BACKGROUND: Type A behaviour and, more specifically, hostility and anger have
      been associated with increased risk of coronary heart disease (CHD). But less
      attention has been paid to other features of personality. Our aim was to assess
      whether a submissiveness trait, which is independent of hostility, was related to
      future risk of CHD in the general population. METHODS: The Edinburgh Artery Study
      is a cohort study of a random sample of 809 men and 783 women aged 55 to 74
      years. At the baseline examination in 1988, we administered the Bedford-Foulds
      Personality Deviance Scales. The participants were followed up for 5 years for
      cardiovascular events. Criteria to define events were adapted from the American
      Heart Association. Events were ascertained from the information and Statistics
      Division of the Scottish Office Home and Health Department, general
      practitioners, the UK National Health Service Central Register, annual
      questionnaires to the participants, and the second examination at the end of
      follow-up. FINDINGS: During follow-up, 57 (7.0%) men and 28 (3.6%) women had non
      fatal myocardial infarctions; 25 (3.1%) men and 8 (1.0%) women had fatal
      myocardial infarctions; and 48 (5.9%) men and 41 (5.2%) women developed angina
      pectoris. We found that mean submissiveness scores were significantly higher in
      men and women who did not have a non-fatal myocardial infarction than in those
      who did (18.88 [SE 0.15] vs 17.70 [0.40], p = 0.023 in men; 20.76 [0.17] vs 18.18
      [0.86], p = 0.002 in women). In multiple logistic-regression models,
      submissiveness remained independently associated with risk of myocardial
      infarction in women only; a decreased risk of both non-fatal myocardial
      infarction (relative risk 0.59 [95% CI 0.40-0.85]) and, to a lesser extent, total
      myocardial infarction (0.69 [0.27-0.96]), was associated with an increase of 1 SD
      in submissiveness. INTERPRETATION: The personality trait of submissiveness may be
      protective against non-fatal myocardial infarction, particularly in women. A
      better understanding is required of the complicated effects of personality on CHD
      development.

PMID- 9284776
TI  - HIV-1 infection associated with abnormal vaginal flora morphology and bacterial
      vaginosis.
AB  - BACKGROUND: In-vitro research has suggested that bacterial vaginosis may increase
      the survival of HIV-1 in the genital tract. Therefore, we investigated the
      association of HIV-1 infection with vaginal flora abnormalities, including
      bacterial vaginosis and depletion of lactobacilli, after adjustment for sexual
      activity and the presence of other sexually transmitted diseases (STDs). METHODS:
      During the initial survey round of our community-based trial of STD control for
      HIV-1 prevention in rural Rakai District, southwestern Uganda, we selected 4718
      women aged 15-59 years. They provided interview information, blood for HIV-1 and
      syphilis serology, urine for detection of Chlamydia trachomatis and Neisseria
      gonorrhoeae, and two self-administered vaginal swabs for culture of Trichomonas
      vaginalis and gram-stain detection of vaginal flora, classified by standardised,
      quantitative, morphological scoring. Scores 0-3 were normal vaginal flora
      (predominant lactobacilli). Higher scores suggested replacement of lactobacilli
      by gram-negative, anaerobic microorganisms (4-6 intermediate; 7-8 and 9-10
      moderate and severe bacterial vaginosis). FINDINGS: HIV-1 frequency was 14.2%
      among women with normal vaginal flora and 26.7% among those with severe bacterial
      vaginosis (p < 0.0001). We found an association between bacterial vaginosis and
      increased HIV-1 infection among younger women, but not among women older than 40
      years; the association could not be explained by differences in sexual activity
      or concurrent infection with other STDs. The frequency of bacterial vaginosis was
      similar among HIV-1-infected women with symptoms (55.0%) and without symptoms
      (55.7%). The adjusted odds ratio of HIV-1 infection associated with any vaginal
      flora abnormality (scores 4-10) was 1.52 (95% CI 1.22-1.90), for moderate
      bacterial vaginosis (scores 7-8) it was 1.50 (1.18-1.89), and for severe
      bacterial vaginosis (scores 9-10) it was 2.08 (1.48-2.94). INTERPRETATION: This
      cross-sectional study cannot show whether disturbed vaginal flora increases
      susceptibility to HIV-1 infection. Nevertheless, the increased frequency of HIV-1
      associated with abnormal flora among younger women, for whom HIV-1 acquisition is
      likely to be recent, but not among older women, in whom HIV-1 is likely to have
      been acquired earlier, suggests that loss of lactobacilli or presence of
      bacterial vaginosis may increase susceptibility to HIV-1 acquisition. If this
      inference is correct, control of bacterial vaginosis could reduce HIV-1
      transmission.

PMID- 9284777
TI  - Randomised controlled study of effect of parathyroid hormone on vertebral-bone
      mass and fracture incidence among postmenopausal women on oestrogen with
      osteoporosis.
AB  - BACKGROUND: Small increases in bone mass are commonly seen with existing
      treatments for osteoporosis, which reduce bone remodelling and primarily prevent
      bone loss. Since these drugs reduce but do not eliminate risk of fractures, an
      anabolic agent that would increase bone mass and potentially cure the underlying
      skeletal problem is needed. METHODS: We did a 3-year randomised controlled trial
      to find out the effects of 1-34 human parathyroid hormone (hPTH [1-34], 400 U/25
      micrograms daily subcutaneously) in postmenopausal women with osteoporosis taking
      hormone-replacement therapy (n = 17). The controls were women taking hormone
      replacement therapy only (n = 17). The primary outcome was bone-mineral density
      of the lumbar vertebrae, with bone-mineral density at other sites and vertebral
      fractures as secondary endpoints. FINDINGS: Patients taking hormone-replacement
      therapy and PTH (1-34) had continuous increase in vertebral bone-mineral density
      during the 3 years, whereas there was no significant change in the control group.
      The total increase in vertebral bone-mineral density was 13.0% (p < 0.001); 2.7%
      at the hip (p = 0.05); and 8.0% in total-body bone mineral (p = 0.002). No loss
      of bone mass was found at any skeletal site. Increased bone mass was associated
      with a reduction in the rate of vertebral fractures, which was significant when
      fractures were taken as a 15% reduction in vertebral height (p = 0.04). During
      the first 6 months of treatment, serum osteocalcin concentration, which reflects
      bone formation, increased by more than 55%, whereas excretion of crosslinked n
      telopeptide, which reflects bone resorption, increased by only 20%, which
      suggests some uncoupling of bone formation and resorption. By 6 months, there
      were similar increases in both markers, which gradually returned towards baseline
      as the study progressed. Vertebral bone-mineral density increased most during the
      first year of PTH treatment. INTERPRETATION: We found that PTH has a pronouned
      anabolic effect on the central skeleton in patients on hormone-replacement
      therapy. PTH also increases total-body bone mineral, with no detrimental effects
      at any skeletal site. The increased vertebral mass was associated with a reduced
      rate of vertebral fracture, despite increased bone turnover. Bone-mass changes
      may be consistent with a reduction in all osteoporotic fractures. If confirmed in
      larger studies, these data have important implications for the treatment of
      postmenopausal osteoporosis.

PMID- 9284779
TI  - Recurrent strokes in a 34-year-old man.

PMID- 9284778
TI  - Epidemic of liver disease caused by hydrochlorofluorocarbons used as ozone
      sparing substitutes of chlorofluorocarbons.
AB  - BACKGROUND: Hydrochlorofluorocarbons (HCFCs) are used increasingly in industry as
      substitutes for ozone-depleting chlorofluorocarbons (CFCs). Limited studies in
      animals indicate potential hepatotoxicity of some of these compounds. We
      investigated an epidemic of liver disease in nine industrial workers who had had
      repeated accidental exposure to a mixture of 1,1-dichloro-2,2,2-trifluoroethane
      (HCFC 123) and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124). All nine exposed
      workers were affected to various degrees. Both compounds are metabolised in the
      same way as 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) to form reactive
      trifluoroacetyl halide intermediates, which have been implicated in the
      hepatotoxicity of halothane. We aimed to test whether HCFCs 123 and 124 can
      result in serious liver disease. METHODS: For one severely affected worker liver
      biopsy and immunohistochemical stainings for the presence of trifluoroacetyl
      protein adducts were done. The serum of six affected workers and five controls
      was tested for autoantibodies that react with human liver cytochrome-P450 2E1
      (P450 2E1) and P58 protein disulphide isomerase isoform (P58). FINDINGS: The
      liver biopsy sample showed hepatocellular necrosis which was prominent in
      perivenular zone three and extended focally from portal tracts to portal tracts
      and centrilobular areas (bridging necrosis). Trifluoroacetyl-adducted proteins
      were detected in surviving hepatocytes. Autoantibodies against P450 2E1 or P58,
      previously associated with halothane hepatitis, were detected in the serum of
      five affected workers. INTERPRETATION: Repeated exposure of human beings to HCFCs
      123 and 124 can result in serious liver injury in a large proportion of the
      exposed population. Although the exact mechanism of hepatotoxicity of these
      agents is not known, the results suggest that trifluoroacetyl-altered liver
      proteins are involved. In view of the potentially widespread use of these
      compounds, there is an urgent need to develop safer alternatives.

PMID- 9284780
TI  - Localisation of sensory motor cortex during surgery by changes of cortical
      surface temperature after median nerve stimulation.

PMID- 9284781
TI  - Differential transmission of HIV-1 and HIV-2.

PMID- 9284782
TI  - Growth-monitoring teaching aid to improve mothers' understanding.

PMID- 9284783
TI  - Macrolide-induced Churg-Strauss syndrome in a patient with atopy.

PMID- 9284784
TI  - External hip protectors to prevent osteoporotic hip fractures.

PMID- 9284785
TI  - Long-term colorectal function after postoperative radiotherapy for colorectal
      cancer.

PMID- 9284786
TI  - Treatment of spastic dystonia with transdermal nicotine.

PMID- 9284787
TI  - Haemochromatosis gene mutation in hepatocellular cancer.

PMID- 9284788
TI  - Irradiation protection from hypersensitivity.

PMID- 9284789
TI  - Fever of unknown origin.

PMID- 9284790
TI  - Changing work patterns.
AB  - In the UK and elsewhere radiographers have taken over some of the work
      traditionally done by radiologists and this is blurring the boundaries between
      the two professions. Radiologists may wonder where such changes will lead. This
      article explores the reasons behind these changes, the practical and medicolegal
      constraints, and the effect of such changes on the provision of radiology
      services in the future.

PMID- 9284791
TI  - Art in hospitals: why is it there and what is it for?

PMID- 9284792
TI  - Cytomegalovirus retinitis after initiation of highly active antiretroviral
      therapy.

PMID- 9284794
TI  - Cytomegalovirus retinitis after initiation of highly active antiretroviral
      therapy.

PMID- 9284793
TI  - Cytomegalovirus retinitis after initiation of highly active antiretroviral
      therapy.

PMID- 9284796
TI  - Cytomegalovirus retinitis after initiation of highly active antiretroviral
      therapy.

PMID- 9284797
TI  - Cold exposure and winter mortality in Europe.

PMID- 9284795
TI  - Cytomegalovirus retinitis after initiation of highly active antiretroviral
      therapy.

PMID- 9284798
TI  - Cold exposure and winter mortality in Europe.

PMID- 9284799
TI  - Cold exposure and winter mortality in Europe.

PMID- 9284800
TI  - Carcinoma of the prostate.

PMID- 9284801
TI  - Borna disease virus and neuropsychiatric disorders. The Japan Bornavirus Study
      Group.

PMID- 9284802
TI  - Borna disease virus and neurospsychiatric disorders.

PMID- 9284803
TI  - Liver transplantation in Japanese patients with familial amyloidotic
      polyneuropathy.

PMID- 9284804
TI  - Olanzapine.

PMID- 9284806
TI  - Epidemics of syphilis in the Russian Federation.

PMID- 9284805
TI  - Culture, trauma, and psychotrauma programmes.

PMID- 9284807
TI  - International performance of UK medical institutions.

PMID- 9284808
TI  - Human-to-human transmission of hantaviruses.

PMID- 9284809
TI  - Pyrenean bears.

PMID- 9284810
TI  - Molecular tumor clocks and dynamic phenotype.

PMID- 9284811
TI  - Role of interleukin-6 in the pathogenesis of murine plasmacytoma and human
      multiple myeloma.

PMID- 9284812
TI  - Osteonectin (SPARC) expression in human liver and in cultured human liver
      myofibroblasts.
AB  - Osteonectin/SPARC is a glycoprotein involved in the regulation of cell shape,
      adhesion, migration, and proliferation. It also has complex effects on
      extracellular matrix synthesis and turnover. We found that osteonectin mRNA was
      very abundant in a human liver myofibroblast library. Using Northern and Western
      blot, immunoprecipitation, and radioimmunoassay, we found that cultured liver
      myofibroblasts actively secreted osteonectin. Myofibroblasts are very rare in
      normal liver but proliferate during liver fibrosis where they synthesize
      extracellular matrix components. Thus, we studied the distribution of osteonectin
      in normal and fibrotic human liver using in situ hybridization. Osteonectin mRNA
      expression was weak in normal liver but very high in fibrotic liver within
      fibrous septae and scattered sinusoidal cells. Serial sectioning and double
      staining experiments with an antibody to smooth muscle alpha-actin showed that
      osteonectin transcripts were mostly co-localized with myofibroblasts. In
      conclusion, osteonectin is highly expressed in human liver myofibroblasts in
      culture as well as in human liver fibrosis in vivo. The many biological
      properties of osteonectin make it a candidate effector of human liver
      fibrogenesis.

PMID- 9284813
TI  - Aging accelerates but life-long dietary restriction suppresses apoptosis-related
      Fas expression on hepatocytes.
AB  - Aging enhances apoptosis of hepatocytes under normal physiological conditions and
      increases the susceptibility of hepatocytes to apoptosis whereas life-long
      dietary restriction suppresses the age-enhanced susceptibility to apoptosis. We
      examined the subcellular mechanisms of the age-associated changes and effect of
      dietary restriction using quantitative reverse transcription polymerase chain
      reaction and immunohistochemistry for Fas in the livers of 6- and 24-month-old
      male Fischer 344 rats fed ad libitum or 70% diet restricted. We also analyzed the
      level of ordinary and variant forms of Fas mRNA. The ordinary form of Fas mRNA,
      but not the variant form of Fas mRNA, significantly increased with age. Dietary
      restriction significantly suppressed the ordinary form of Fas mRNA in advanced
      age. Aging enhanced Fas immunoreactivity in the hyperplastic bile epithelium and
      hepatocytes whereas dietary restriction suppressed it. Our findings indicate that
      Fas protein, particularly the ordinary form of Fas, is involved in age-associated
      apoptosis of hepatocytes. Fas overexpression in advanced age may explain the age
      enhanced susceptibility to apoptosis. Our results also suggest that dietary
      restriction suppresses Fas overexpression, resulting in a reduction of the age
      enhanced susceptibility to apoptosis.

PMID- 9284814
TI  - Expression of gelatinase B and the extracellular matrix metalloproteinase inducer
      EMMPRIN in benign and malignant pigment cell lesions of the skin.
AB  - By the degradative effect on basement membrane collagen type IV, matrix
      metalloproteinases (MMPs) or gelatinases are important in the early invasion of
      malignant tumors. These enzymes may be released by the tumor cells themselves or
      may be derived from nearby fibroblasts that have been stimulated by the
      extracellular MMP inducer EMMPRIN. We studied the distribution of 92-kd
      gelatinase B (MMP-9) and of EMMPRIN in 33 benign and 41 malignant, paraffin
      embedded pigment cell lesions using immunohistochemistry and monoclonal
      antibodies. In benign pigment cell lesions, EMMPRIN but not gelatinase B was
      expressed in cellular blue nevi whereas all other benign lesions, including
      common blue nevi, were negative. In malignant melanomas (MMs), both gelatinase B
      and EMMPRIN were variably expressed in the pure and invasive radial growth phase
      but not in the vertical growth phase. All lentigo maligna cases and all
      metastatic lesions were negative. Of MMs with thickness < 1.6 mm, 63% expressed
      gelatinase B and 70% expressed EMMPRIN, whereas in MMs with > 1.6 mm thickness,
      only 10% expressed gelatinase B and only 25% expressed EMMPRIN. We conclude that
      early invasion of MM is associated with de novo expression of gelatinase B and
      EMMPRIN by neoplastic melanocytes. Expression of EMMPRIN and MMP-9 may be partly
      responsible for the stromal changes observed in thin MM. Their absence in the
      vertical growth phase and in metastatic lesions suggests that other factors are
      involved in tissue degradation during later stages of tumor progression in MM.
      The lack of both gelatinase B and EMMPRIN in lentigo maligna may contribute to
      the indolent behavior of this type of pigment cell lesion.

PMID- 9284815
TI  - Involvement of endothelial PECAM-1/CD31 in angiogenesis.
AB  - The adhesive interactions of endothelial cells with each other and the adhesion
      receptors that mediate these interactions are probably of fundamental importance
      to the process of angiogenesis. We therefore studied the effect of inhibiting the
      function of the endothelial cell-cell adhesion molecule, PECAM-1/ CD31, in rat
      and murine models of angiogenesis. A polyclonal antibody to human PECAM-1, which
      cross-reacts with rat PECAM-1, was found to block in vitro tube formation by rat
      capillary endothelial cells and cytokine-induced rat corneal neovascularization.
      In mice, two monoclonal antibodies against murine PECAM-1 prevented vessel growth
      into subcutaneously implanted gels supplemented with basic fibroblast growth
      factor (bFGF). Taken together these findings provide evidence that PECAM-1 is
      involved in angiogenesis and suggest that the interactions of endothelial cell
      cell adhesion molecules are important in the formation of new vessels.

PMID- 9284816
TI  - Effect of host microenvironment on the microcirculation of human colon
      adenocarcinoma.
AB  - It is generally accepted that the host microenvironment influences tumor biology.
      There are discrepancies in growth rate, metastatic potential, and efficacy of
      systemic treatment between ectopic and orthotopic tumors. Liver is the most
      common and critical site of distant metastasis of colorectal carcinoma.
      Tumorigenicity and efficacy of chemotherapeutic agents in colorectal tumors are
      different in liver and subcutaneous sites. Thus, we hypothesize that the liver
      (orthotopic) versus subcutaneous (ectopic) microenvironment would have different
      effects on the angiogenesis and maintenance of the microcirculation of colorectal
      tumor. To this end, we developed a new method to monitor and to quantify
      microcirculatory parameters in the tumor grown in the liver. Using this approach,
      we compared the microcirculation of LS174T, a human colon adenocarcinoma,
      metastasized to the liver with that of the host liver vessels and that of the
      same tumor grown in the subcutaneous space. In the liver metastasis model, 5 x
      10(6) LS174T cells were injected into the spleen of nude mice. Four to eight
      weeks later, the liver with metastatic tumors was exteriorized and placed on a
      special stage and observed under an intravital fluorescence microscope. The
      dorsal skinfold chamber model was used to study the subcutaneous tumors. Red
      blood cell velocity, vessel diameter, density, permeability, and leukocyte
      endothelial interactions were measured using fluorescence microscopy and image
      analysis. Vascular endothelial growth factor/ vascular permeability factor
      (VEGF/VPF) mRNA expression was determined by the Northern blot analysis. LS174T
      tumor foci in the liver had tortuous vascular architecture, heterogeneous blood
      flow, significantly lower vascular density, and significantly higher vascular
      permeability than normal liver tissue. Tumors grown in the liver had
      significantly lower vessel density, especially in the center coincident with
      central necrosis, than the subcutaneous tumors. The frequency distribution of
      vessel diameters of liver tumor was slightly shifted to smaller size compared
      with that of subcutaneous tumor. Leukocyte rolling in liver tumor was twofold
      lower than that in subcutaneous tumor. These physiological findings were
      consistent with the measurement of VEGF/VPF in that the VEGF/VPF mRNA level was
      lower in the liver tumor than that in the subcutaneous tumor. However,
      macromolecular vascular permeability in the liver tumor was significantly higher
      than in the subcutaneous tumor. Liver sinusoidal endothelial cells, the origin of
      liver tumor vessel endothelium, are known to be fenestrated and not to have a
      basement membrane, suggesting that the difference in endothelial cell origin may
      explain the difference in tumor vascular permeability in two sites. These
      findings demonstrate that liver microenvironment has different effects on some
      aspects of the tumor angiogenesis and microcirculation compared with the
      subcutaneous tissues. The new model/method described in this paper has
      significant implications in two research areas: 1) the liver microenvironment and
      its effect on tumor pathophysiology in conjunction with cytokine/ growth factor
      regulation and 2) the delivery of drugs, cells, and genes to liver tumors.

PMID- 9284817
TI  - Defective development of pristane-oil-induced plasmacytomas in interleukin-6
      deficient BALB/c mice.
AB  - Interleukin (IL)-6 is known to be an essential growth factor for myeloma cells,
      both in vitro and in vivo. In mice, IL-6 is required for development of B cell
      tumors upon infection with a retrovirus expressing the myc/raf oncogenes. In the
      present study, we used the pristane-oil-induced plasmacytoma model, which more
      closely mimics tumor transformation and progression in human multiple myeloma.
      Also using this system, we found that IL-6-deficient BALB/c mice are protected
      against tumor development. Although the pristane-induced inflammatory reaction
      was less pronounced in IL-6-deficient mice versus their wild-type littermates,
      both B cell differentiation and plasma cell formation took place, and even
      morphological evidence of plasma cell transformation was detected, albeit at a
      low frequency. However, in the absence of IL-6, there were never signs of
      uncontrolled proliferation of either normal B lymphocytes or tumor cells,
      suggesting that the role of IL-6 in murine plasmacytoma and possibly also in
      human multiple myeloma is to ensure abnormal survival and proliferation of
      previously transformed tumor cells and therefore tumor development and
      progression.

PMID- 9284819
TI  - Relationship of polymorphonuclear leukocytes to capillary dropout in the human
      diabetic choroid.
AB  - Capillary dropout is an initial event in diabetic retinopathy, but the etiology
      is unknown. Recent evidence suggests that similar events may occur in the
      diabetic choroid. We have developed a method to evaluate the relationship between
      the polymorphonuclear leukocytes (PMNs) and capillary dropout in the human
      diabetic choroid using alkaline phosphatase (APase) histochemistry to label blood
      vessels and nonspecific esterase activity to identify PMNs. The number and
      distribution of PMNs in diabetic and nondiabetic choroidal capillaries
      (choriocapillaris) were analyzed in the flat perspective and the tissue then flat
      embedded in glycol methacrylate for histological sectioning. The total number of
      PMNs was increased within the choriocapillaris in five diabetic eyes (170.9 +/-
      12.9 PMNs/mm2 of choroid) compared with five nondiabetic eyes (84.2 +/- 16.9
      PMNs/mm2; P < 0.001). PMNs were almost always within blood vessel lumens and not
      in interstitial tissue. In the diabetic choroid, increased numbers of PMNs were
      present in areas of choriocapillaris with pathological changes (loss in APase
      activity and choroidal neovascularization) compared with nonpathological
      choriocapillaris (205.1 +/- 46.9 PMNs/mm2 in pathological versus 152.3 +/- 23.4
      PMNs/mm2 in nonpathological areas; P < 0.001). PMNs were often queued up within
      the lumens of capillaries, demonstrating loss in APase activity. We have observed
      an increased number of PMNs in diabetic choroid compared with control nondiabetic
      choroids, and PMNs in diabetic choroid were associated with loss in APase
      activity, which was related to loss in viable endothelial cells. The results
      suggest that PMNs contribute to vaso-occlusive processes and endothelial cell
      injury in the diabetic choroid.

PMID- 9284818
TI  - Monoclonality of smooth muscle cells in human atherosclerosis.
AB  - Atherosclerotic plaques contain a large monoclonal population of cells.
      Monoclonality could arise by somatic mutation, selection of a pre-existing
      lineage, or expansion of a pre-existing (developmental) clone. To determine the
      monoclonal cell type in plaque and learn when monoclonality arises, we studied X
      chromosome inactivation patterns using methylation of the X-linked human androgen
      receptor gene. Assays based on polymerase chain reaction were performed on
      samples of known cellular composition, microdissected from histological sections
      of human arteries. In atherosclerotic vessels, the majority of medial samples
      (7/11 coronary and 2/3 aortic) showed balanced (paternal and maternal) patterns
      of X inactivation, indicating polyclonality. In contrast, most samples of plaque
      smooth muscle cells showed a single pattern of X inactivation (3/4 aortic plaques
      and 9/11 coronary plaques; P < 0.01 versus media), indicating that plaque smooth
      muscle cells are monoclonal. Samples of plaque containing inflammatory or
      endothelial cells showed balanced X inactivation, also demonstrating
      polyclonality. Multiple plaques from a given patient showed no bias toward one
      allele, indicating there was no X-linked selection of cells during plaque growth.
      To determine whether plaques might arise from pre-existing clones (large X
      inactivation patches), we then studied 10 normal coronaries with diffuse intimal
      thickening. Six of the ten coronaries showed skewed X inactivation patterns in
      normal media and intima, suggesting the patch size in normal arteries is
      surprisingly large. Thus, smooth muscle cells constitute the monoclonal
      population in atherosclerotic plaques. The finding that normal arteries may have
      large X inactivation patches raises the possibility that plaque monoclonality may
      arise by expanding a pre-existing clone of cells rather than generating a new
      clone by mutation or selection.

PMID- 9284820
TI  - Differential expression and localization of insulin-like growth factors I and II
      in cutaneous wounds of diabetic and nondiabetic mice.
AB  - Insulin-like growth factor (IGF)-I has profound effects on tissue repair. IGF-II
      is felt to exert its influence predominately during fetal development. The
      purpose of this study was to localize and quantify the expression of IGF-I and
      IGF-II mRNA and protein during early wound healing in diabetic and nondiabetic
      mice. The hypothesis is that IGF-I and IGF-II are up-regulated in the healing
      wound, but their expression is inhibited in diabetics. Full-thickness cutaneous
      wounds were made on genetically diabetic (C57BL/ KsJ-db/db) mice and their
      nondiabetic littermates. At various times after wounding, one-half of each wound
      was fixed and paraffin embedded for immunohistochemistry and in situ
      hybridization. The other half was flash-frozen for quantification of IGF mRNA by
      competitive reverse transcriptase polymerase chain reaction and protein by
      radioimmunoassay. IGF-I mRNA rose sharply in nondiabetics at day 3. Expression in
      diabetic wounds was significantly delayed until 14 days after wounding. Even
      then, diabetic IGF-I mRNA levels were 50% less than those in the nondiabetics at
      their peak. Although not usually considered active in adult life, IGF-II mRNA
      expression was augmented after wounding, peaking at 3 days in nondiabetics. As
      with IGF-I, diabetic wounds exhibited a delay in IGF-II mRNA expression, with
      maximal levels at 10 days after wounding. Interestingly, peak concentrations of
      IGF-II mRNA were four times greater in diabetics versus nondiabetics. Trends in
      IGF-I protein expression followed the patterns of mRNA expression. IGF-I levels
      in nondiabetics were initially double those in diabetics and peaked at 5 days.
      Diabetic wound concentrations of IGF-I did not peak until 21 days after wounding,
      at which time they rose to nondiabetic levels. IGF-I and IGF-II proteins were
      localized to the advancing epithelial edge, to the epithelial cells of adjacent
      hair follicles, and to the granulation tissue of the wounds. IGF-I and IGF-II
      mRNA expression was noted in the epithelial edge and in the hair follicles
      adjacent to the wound, paralleling protein expression. Both IGF-I and IGF-II are
      up-regulated in the healing wound. A delay in IGF-I and -II presence is noted in
      the diabetic wound. The impairment in tissue repair in diabetic animals is at
      least partially due to a deficiency in the production of the IGFs.

PMID- 9284821
TI  - The kidneys of mice with autoimmune disease acquire a
      hypofibrinolytic/procoagulant state that correlates with the development of
      glomerulonephritis and tissue microthrombosis.
AB  - Quantitative reverse transcription polymerase chain reaction and in situ
      hybridization were employed to investigate the expression of tissue-type and
      urokinase-type plasminogen activators (t-PA and u-PA, respectively), of their
      specific inhibitor (PAI-1), and of the procoagulant molecule tissue factor (TF)
      in tissues from mice that develop autoimmune disease (MRL lpr/lpr). A dramatic
      increase in PAI-1 activity in plasma and in PAI-1 mRNA in the kidneys was
      observed in these mice, and this increase appeared to correlate with the
      progression of lupus nephritis. The increase in PAI-1 mRNA was relatively
      specific for the kidney as little or no change was observed in most other
      tissues. One exception was the brain where PAI-1 mRNA was also significantly
      higher in the diseased mice. In addition to these changes in PAI-1, decreases in
      u-PA mRNA and increases in TF mRNA were demonstrated in kidneys from the lupus
      prone mice. These changes also correlated with the development of lupus nephritis
      and with spontaneous glomerular and peritubular fibrin deposition in the
      nephritic kidney. In this regard, the MRL lpr/lpr mice were found to be
      considerably more sensitive to endotoxin than the normal controls, developing
      fibrin deposits in the kidneys and other tissues at 10- to 20-fold lower
      concentrations of this toxic agent. The increase in PAI-1 and TF mRNAs and the
      decrease in u-PA mRNA in the kidneys of MRL lpr/lpr mice suggests that changes in
      the expression of these genes may promote the formation of microthrombi and thus
      contribute to the progression of lupus nephritis in this model.

PMID- 9284822
TI  - Oncogenic transformation and inhibition of adipocytic conversion of preadipocytes
      by TLS/FUS-CHOP type II chimeric protein.
AB  - Myxoid liposarcomas are characterized by t(12; 16)(q13;p11) translocation and
      expression of TLS/ FUS-CHOP chimeric transcripts (types I to III). Among these,
      the type II transcript is expressed in the majority of cases of myxoid and round
      cell liposarcoma. To investigate the function of the type II chimeric protein, we
      obtained stable transformants of ST-13, a murine preadipocytic cell line, which
      express TLS/FUS-CHOP type II protein (ST-TC) or CHOP protein (ST-C) as well as
      vector-transfected controls (ST-V). ST-TC and ST-C cells showed almost complete
      or partial resistance to adipogenic conversion by insulin and thiazolidinedione,
      respectively. Induction by adipogenic stimulation of the adipocytic genes such as
      C/EBP alpha, aP2, and adipsin was almost totally suppressed in the ST-TC cells,
      whereas in ST-C cells C/EBP alpha alone was induced without induction of aP2 and
      adipsin. Transcriptional suppression of the C/EBP alpha gene in ST-TC cells was
      suggested by the results of chloramphenicol acetyltransferase (CAT) assay showing
      a significantly lower C/EBP alpha promoter activity compared with findings in ST
      C and ST-V cells. Failure to rescue adipogenic conversion by ectopic expression
      of C/EBP alpha in ST-TC cells suggested a functional impairment of C/EBP alpha to
      induce expression of downstream genes. TLS/FUS-CHOP type II protein showed
      transforming activity, as evidenced by loss of contact inhibition of growth,
      anchorage-independent growth in soft agar, and tumor formation in nude mice,
      showing typical histological features of myxoid liposarcoma seen in humans. These
      findings suggest important roles for TLS/FUS-CHOP type II protein in the
      oncogenesis of myxoid liposarcoma.

PMID- 9284823
TI  - The cell-cell adhesion receptor Mel-CAM acts as a tumor suppressor in breast
      carcinoma.
AB  - Mel-CAM (MUC18 or CD146) is a cell adhesion molecule sharing sequence homology
      with members of the immunoglobulin gene superfamily. Mel-CAM was originally
      described as a marker associated with invasion and metastasis in melanoma. We
      determined here the distribution and biological significance of Mel-CAM in
      normal, benign proliferative, and neoplastic breast ductal epithelium. Using a
      Mel-CAM-specific monoclonal antibody, we, immunohistochemically demonstrate Mel
      CAM expression in 14 of 14 (100%) normal breast epithelia and benign
      proliferative ductal epithelial lesions, whereas Mel-CAM expression can only be
      focally detected in 12 of 72 (17%) breast carcinomas. Solid-phase cell adhesion
      assay revealed that breast carcinoma cells in culture express the ligand for Mel
      CAM. Transfection of Mel-CAM cDNA into breast carcinoma cells induces a more
      cohesive cell growth pattern and establishes smaller tumors in immunocompromised
      mice than mock transfectants. In conclusion, Mel-CAM is distributed throughout
      normal and benign proliferative mammary ductal epithelium, but it is frequently
      lost in carcinomas; it functions as a heterophilic cell-cell adhesion molecule in
      breast epithelium, and loss of Mel-CAM expression in breast carcinoma may be an
      important step for tumor progression.

PMID- 9284825
TI  - Amplification of the c-erbB-2 (HER-2/neu) gene in gastric cancer cells. Detection
      by fluorescence in situ hybridization.
AB  - Amplification of the c-erbB-2 gene was examined in 120 gastric adenocarcinomas by
      dual-color fluorescence in situ hybridization (FISH) using probes for centromere
      17 and the 17q11.2-12. The results were compared with Southern blot analysis and
      immunohistochemistry of c-erbB-2 overexpression. FISH was successful in 105
      tumors, and the amplification was found in 19 tumors. FISH on 17 tumors revealed
      high-level amplification; in 15, the predominant cancer populations had amplified
      c-erbB-2 gene with the signals forming one or two clusters, indicating that the
      amplified gene was present in homogeneously staining regions. In two tumors, most
      cancer cells had multiple scattered c-erbB-2 signals, indicating that the
      amplicon was within double-minute chromosomes. The other two tumors had a few
      additional copies of the c-erbB-2 gene. Seventeen tumors had increased numbers of
      the gene probably due to polysomy 17, and sixty-nine tumors had no aberrations of
      chromosome 17. Immunohistochemically, distinct membrane staining was found only
      in the 17 tumors with the high-level amplification. It is concluded that, in
      gastric adenocarcinomas, high-level amplification produces the c-erbB-2 gene
      principally in homogeneously staining region form and occasionally in double
      minute form and is thought to control the over-expression of the protein in the
      cytoplasmic membrane.

PMID- 9284824
TI  - Chromosome 8p deletions are associated with invasive tumor growth in urinary
      bladder cancer.
AB  - Alterations of chromosome 8, including deletions of 8p, occur frequently in many
      tumors. In this study, fluorescence in situ hybridization was used to study the
      relationship between 8p deletions, 8q gains, and phenotype in bladder cancer.
      Cells from 87 tumors were examined by dual-labeling fluorescence in situ
      hybridization with a centromere 8 probe (pJM12) and P1 probes for 8p22, 8p12,
      8q12, and 8q24. Both 8p22 deletions and 8q24 gains were strongly associated with
      tumor phenotype. There was a marked difference in 8p22 deletions between
      noninvasive (pTa) tumors (3/33) and minimally invasive (pT1) tumors (8/19; P =
      0.005) whereas there was no significant difference between pT1 and muscle
      invasive (pT2-4) tumors (19/35; P = 0.3926). Six tumors with 8p22 deletion were
      examined at 8p12. Three of these tumors showed no 8p12 deletion, narrowing down
      the site of a putative tumor suppressor gene distal to 8p12. In one other case,
      there was a marked increase in 8p12 copy number (> 40 per cell; amplification),
      suggesting the presence of an oncogene involved in bladder cancer at 8p12. The
      marked difference in 8p22 deletions between noninvasive (pTa) and minimally
      invasive (pT1) tumors is consistent with a role of a putative tumor suppressor
      gene on 8p for development of invasive tumor phenotype.

PMID- 9284827
TI  - Lymphocyte apoptosis during early phase of Listeria infection in mice.
AB  - During the acute phase of growth of Listeria monocytogenes in spleen and lymph
      nodes, the infective foci consist of macrophages and neutrophils accompanied by
      extensive death of lymphocytes. Many of the lymphocytes die by apoptosis. The
      lesions are found by 48 hours after infection and can regress with time.
      Depending on the dose, the infected foci can be restricted to the thymus
      dependent areas or can occupy the entire lymphoid tissue. The Listeria in the
      lesions are primarily found inside macrophages, but a few are extracellular amid
      cellular debris. Lymphocyte death appears to be an obligatory step in primary
      Listeria infection, the extent of which is controlled by the early restriction of
      Listeria growth by the innate cellular system.

PMID- 9284826
TI  - Overexpression of the growth-hormone-releasing hormone gene in acromegaly
      associated pituitary tumors. An event associated with neoplastic progression and
      aggressive behavior.
AB  - The clinical behavior of growth hormone (GH)-producing pituitary tumors is known
      to vary greatly; however, the events underlying this variability remain poorly
      understood. Herein we demonstrate that tumor overexpression of the GH-releasing
      hormone (GHRH) gene is one prognostically informative event associated with the
      clinical aggressiveness of somatotroph pituitary tumors. Accumulation of GHRH
      mRNA transcripts was demonstrated in 91 of a consecutive series of 100
      somatotroph tumors by in situ hybridization; these findings were corroborated by
      Northern analysis and reverse transcriptase polymerase chain reaction, and
      protein translation was confirmed by Western blotting. By comparison, transcript
      accumulation was absent or negligibly low in 30 normal pituitary glands. GHRH
      transcripts were found to preferentially accumulate among clinically aggressive
      tumors. Specifically, GHRH mRNA signal intensity was 1) linearly correlated with
      Ki-67 tumor growth fractions (r = 0.71; P < 0.001), 2) linearly correlated with
      preoperative serum GH levels (r = 0.56; p = 0.01), 3) higher among invasive
      tumors (P < 0.001), and 4) highest in those tumors in which post-operative
      remission was not achieved (P < 0.001). Using multivariate logistic regression, a
      model of postoperative remission likelihood was derived wherein remission was
      defined by the single criterion of suppressibility of GH levels to less than 2
      ng/ml during an oral glucose tolerance test. In this outcome model, GHRH mRNA
      signal intensity proved to be the most important explanatory variable overall,
      eclipsing any and all conventional clinicopathological predictors as the single
      most significant predictor of postoperative remission; increases in GHRH mRNA
      signal were associated with marked declines in remission likelihood. The
      generalizability of this outcome model was further validated by the model's
      significant performance in predicting postoperative remission in a random sample
      of 30 somatotroph tumors treated at another institution. These data indicate that
      overexpression of GHRH gene is an event associated with the neoplastic
      progression and clinical aggressiveness of somatotroph adenomas. More generally,
      these data merge essential elements of the hypothalamic and pituitary hypotheses
      of pituitary tumorigenesis, providing for a more unified concept of neoplastic
      progression in the pituitary.

PMID- 9284828
TI  - Pathogenesis of SIV encephalitis. Selection and replication of neurovirulent SIV.
AB  - To investigate the viral and host factors that contribute to neurological
      disease, nine macaques were intravenously co-inoculated with SIV/DeltaB670, a
      primary isolate of SIV consisting of at least 21 different genotypes, and SIV/17E
      Fr, a neurovirulent recombinant clone. CD4+ cell counts and antigenemia were
      measured throughout infection. The SIV env V1 region was amplified from brain and
      peripheral blood mononuclear cell DNA to compare the genotypes present in brain
      and blood. Seven of the 9 macaques (78%) developed typical SIV-associated
      neurological lesions classified as severe (4 macaques), moderate (2 macaques), or
      mild (1 macaque) with a mean time to euthanasia of 7 months. Macaques with severe
      neurological lesions progressed more rapidly, with a mean time to euthanasia of 3
      6 months. SIV/17E-Fr was detected in brain homogenates from all four macaques
      with severe encephalitis, and in three of the four, SIV/17E-Fr was the only
      genotype identified in the central nervous system. Macaques with less severe or
      no neurological lesions usually had one of various genotypes of SIV/DeltaB670 in
      brain. A variety of genotypes of SIV/DeltaB670 and SIV/17E-Fr were detected in
      peripheral blood mononuclear cells throughout infection. Macaques with severe
      neurological lesions had the most precipitous declines in CD4+ cell counts, the
      highest levels of antigenemia, and the greatest expression of viral RNA and
      protein in the central nervous system. Macaca nemestrina were more likely to
      develop severe neurological lesions than M. mulatta or M. fascicularis (P =
      0.048). This study demonstrated that neurovirulent strains within the virus swarm
      can selectively enter and become established in the central nervous system and
      that the neurological lesions that develop are correlated with the development of
      host immunosuppression. The species differences in severity of neurological
      lesions seen in this study suggest that host factors are also important in
      determining the outcome of lentiviral infection.

PMID- 9284829
TI  - Epstein-Barr virus latent membrane protein-1 oncogene deletion in post
      transplantation lymphoproliferative disorders.
AB  - Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) is a multifunctional
      oncoprotein. A 30-bp deletion of the 3' end of the LMP1 gene (del-LMP1) has been
      identified in some EBV isolates. This deleted LMP1 gene encodes a protein,
      altered on the carboxy terminus, which is thought to have greater oncogenic
      potential than the wild type. Recently, it was suggested that del-LMP1 plays a
      role in the development of malignant lymphomas occurring in immunocompromised
      patients. To further elucidate the role of del-LMP1 in post-transplantation
      lymphoproliferative disorders (PT-LPDs) we analyzed 58 PT-LPD lesions from 36
      heart and kidney organ transplant recipients. Overall, del-LMP1 was detected in
      44% of the cases. Four plasmacytic hyperplasias (36%), eight polymorphic B-cell
      hyperplasias/polymorphic B-cell lymphomas (38%), and five malignant
      lymphomas/multiple myelomas (71%) exhibited del-LMP1. Two of the three patients
      displaying disease progression showed wild-type LMP1 gene (w-LMP1) and one showed
      del-LMP1. LMP1 status remained the same in all three patients during disease
      progression. In patients undergoing biopsy of multiple separate PT-LPD lesions
      representing different clonal lymphoid proliferations, LMP1 status was the same
      in all of the lesions in each patient. Furthermore, although the polyclonal
      lesions harbor multiple EBV infectious events, they either showed w- or del-LMP1
      but not both. Analysis of the tissues without an apparent PT-LPD (peripheral
      blood, bone marrow, or colon) revealed EBV and LMP1 type identical to that found
      in the lesions. In conclusion, the presence or absence of del-LMP1 in PT-LPDs
      does not correlate with the histopathological category or the malignant nature of
      the lymphoid proliferation. LMP1 status does not change during disease
      progression and is the same within multiple lesions occurring in the same patient
      regardless of their clonal relationship. These findings suggest that 1) EBV
      infection in patients with PT-LPDs occurs with a w- or del-LMP1-type EBV isolate
      and does not change once a patient acquires the virus and 2) the infection is an
      early event in the development of PT-LPDs and transformation is induced
      regardless of the type of LMP1.

PMID- 9284830
TI  - Depletion of eosinophil infiltration by anti-IL-5 monoclonal antibody (TRFK-5)
      accelerates open skin wound epithelial closure.
AB  - Wound healing is critical to the survival of the species after injury. Using
      hamsters as an experimental model, we have shown that eosinophils infiltrate
      prominently into skin wounds and that they express transforming growth factor
      alpha and -beta 1 mRNAs and proteins. We hypothesized that eosinophils are
      important in wound healing. As no animal model is genetically deficient in
      eosinophils, a suitable way to test the hypothesis is to selectively reduce
      and/or deplete the influx of eosinophils into the wound sites. In this study, we
      report that anti-interleukin-5 monoclonal antibody (TRFK-5) treatment can deplete
      eosinophils in cutaneous healing wounds. We found that wound closure by re
      epithelialization in the experimental group was 4 days faster than in the control
      group (P < 0.01). The density of eosinophils in day-9 wounds was significantly
      lower in the experimental group (P < 0.01). Wound-associated eosinophils in each
      of the TRFK-5-treated hamsters were depleted to the level comparable to unwounded
      hamster skin. These results demonstrate that anti-interleukin-5 monoclonal
      antibody treatment can effectively decrease eosinophil infiltration into hamster
      cutaneous healing wounds and indicate a role for eosinophils in negatively
      affecting wound re-epithelialization.

PMID- 9284831
TI  - Analysis of cell damage and proliferation in Helicobacter pylori-infected human
      gastric mucosa from patients with gastric adenocarcinoma.
AB  - Helicobacter pylori (HP) infection, a cause of multifocal atrophic gastritis, is
      considered an important factor related to the evolution of the human gastric
      mucosa from normal to intestinal-type adenocarcinoma. We examined cell
      proliferation and both double and single strand DNA damage in situ in 35 patients
      undergoing gastrectomy for adenocarcinoma with HP-infected gastric mucosa by
      immunolocalization of Ki-67, terminal deoxynucleotidyl transferase-mediated dUTP
      biotin nick end labeling, and in situ nick translation. We also studied the
      distribution of intraepithelial neutrophils by elastase immunolocalization. HP
      infection was confirmed in all cases by serum anti-HP antibodies, ureas testing,
      and histopathological examination. HP-infected gastric mucosa was classified
      according to the degree of inflammation and intestinal metaplasia. Ki-67,
      terminal deoxynucleotidyl transferase-mediated labeling, in situ nick
      translation, and intraepithelial neutrophil indices all increased with the
      progression of gastritis and were highest in glands with incomplete intestinal
      metaplasia. All indices were lowest in gastric glands with complete intestinal
      metaplasia. Significant positive correlations were observed among these markers.
      Increased proliferative activity in HP-associated chronic gastritis in response
      to cell damage or injury was clearly demonstrated, suggesting that both HP
      associated toxins and intraepithelial neutrophils are important in HP-related
      gastric epithelial injury. Increased cell turnover associated with incomplete
      intestinal metaplasia may result in DNA instability and subsequent development of
      intestinal-type gastric adenocarcinoma in HP-infected mucosa.

PMID- 9284832
TI  - Increased levels of endothelin-1 and differential endothelin type A and B
      receptor expression in scleroderma-associated fibrotic lung disease.
AB  - In addition to their vasoactive action, endothelins are potent peptides in the
      regulation of both cell proliferation and the turnover of extracellular matrix.
      Using immunohistochemical, autoradiographic, and molecular analyses, we have
      studied the localization and expression of endothelin-1 and endothelin A (ETA)
      and B (ETB) receptors in scleroderma-associated fibrotic lung disease. Increased
      ET-1 immunoreactivity was found in sclerotic tissue compared with control and was
      associated with the vasculature, pulmonary interstitium, and bronchial and
      alveolar epithelium. Microautoradiographic analysis after 125I-labeled ET-1
      binding showed a two- to threefold increase in the expression of total ET-1
      receptors in scleroderma lung tissue localized to the alveolar epithelium and the
      pulmonary interstitium which was composed of mainly fibroblastic cells with
      macrophages and some microvessels. RNAse protection assay revealed significantly
      reduced ETA receptor and slightly raised ETB message levels in systemic sclerosis
      lung. Surface expression of functional ET receptors was examined by targeted
      receptor blocking using mixed and receptor-subtype-selective ligands. A
      consistent decrease in ETA receptor binding sites was noted primarily within the
      interstitium and vasculature, in contrast to a slight increase in ETB receptors.
      Elevated ET-1 and the cell-specific pattern of endothelin receptor expression
      suggest that the endothelins may represent important mediators that influence the
      pathology of scleroderma-associated lung disease and other fibrotic conditions.

PMID- 9284833
TI  - Effects of epidermal growth factor and dimethylhydrazine on crypt size, cell
      proliferation, and crypt fission in the rat colon. Cell proliferation and crypt
      fission are controlled independently.
AB  - Crypt fission is now established as an important mechanism of intestinal growth
      and regeneration. It has been proposed that increased crypt size is the stimulus
      for crypt fission, because crypts preparing for fission are generally larger.
      Consequently, we investigated the effects of epidermal growth factor (EGF) and
      dimethylhydrazine, which are both known to stimulate crypt cell proliferation, on
      crypt fission in the rat intestine. We also examined whether the effects of EGF
      on both proliferation and crypt fission are modified by the pretreatment with
      dimethylhydrazine for 16 weeks, dimethylhydrazine was then discontinued for 8
      weeks, followed by intravenous infusion of EGF for 1 week. There were four
      groups: vehicle alone, EGF alone, dimethylhydrazine alone, and dimethylhydrazine
      followed by EGF infusion. The rats were killed at 25 weeks and rates of
      intestinal crypt cell production, crypt size, and crypt fission were determined.
      Intravenously infused EGF significantly increased crypt cell production rate, but
      the magnitude of the effect decreased from the proximal to the distal colon. EGF
      caused an increase in crypt area, possibly reflecting an increase in crypt size.
      Importantly dimethylhydrazine had no significant effect on crypt cell production
      rate nor on crypt area in the distal colon, but it did cause an increase in crypt
      area in the mid-colon. The crypt fission index was significantly decreased by EGF
      and increased by dimethylhydrazine. There was no qualitative interaction between
      EGF and dimethylhydrazine. These results demonstrate the marked proliferative
      effect of intravenously infused EGF in the colon of orally fed rats, with
      significant site effects (P = 0.0007); the effect was greatest in the proximal
      colon and disappeared in the distal colon. The observation that EGF reduced crypt
      fission indicates that increased cell proliferation, per se, is not a stimulus
      for crypt fission. This is further supported by the observation that
      dimethylhydrazine increases crypt fission in crypts of normal size in the distal
      colon without significantly increasing cell proliferation. These results suggest
      that increasing crypt cellularity by proliferation is not sufficient to induce
      crypt fission, and factors other than increased crypt size by proliferation can
      control crypt fission. It is also probable that cell proliferation and crypt
      fission are independently regulated. Crypt fission appears to play a considerable
      role in the intestinal response to carcinogens.

PMID- 9284834
TI  - Molecular genetic analysis of giant cell glioblastomas.
AB  - Glioblastomas (GBMs) are a heterogeneous group of tumors. Recently, distinct
      molecular genetic alterations have been linked to subgroups of patients with GBM.
      Giant cell (gc)GBMs are a rare variant of GBM characterized by a marked
      preponderance of multinucleated giant cells. Several reports have associated this
      entity with a more favorable prognosis than the majority of GBMs. To evaluate
      whether gcGBM may also represent a genetically defined subgroup of GBM, we
      analyzed a series of 19 gcGBMs for mutations in the TP53 gene for amplification
      of the EGFR and CDK4 genes and for homozygous deletions in the CDKN2A (p16/MTS1)
      gene. Seventeen of nineteen gcGBMs carried TP53 mutations whereas EGFR and CDK4
      gene amplification was seen in only one tumor each and homozygous deletion of
      CDKN2A was not observed at all. The strikingly high incidence of TP53 mutations
      and the relative absence of other genetic alterations groups gcGBM together with
      a previously recognized molecular genetic variant of GBM (type 1 GBM). It is
      tempting to speculate that the better prognosis of gcGBM patients may result from
      the low incidence of EGFR amplification and CDKN2A deletion, changes known for
      their growth-promoting potential.

PMID- 9284835
TI  - Frequent p16INK4 (MTS1) gene inactivation in testicular germ cell tumors.
AB  - The molecular mechanisms responsible for the development of testicular germ cell
      tumors (GCTs) have not as yet been elucidated. The aim of the present study was
      to determine whether genetic alterations of p16INK4 (MTS1) and/or cyclin
      dependent kinase 4 (CDK4) occur in the genesis of these tumors. We have analyzed
      these two genes in 29 testicular GCTs, seminomas, and nonseminomas. None of the
      tumors showed either p16INK4 or CDK4 mutations. Only 1 of the 29 GCTs displayed
      loss of heterozygosity of the p16INK4 gene. No homozygous deletions of p16INK4
      were detected. Evidence of hypermethylation of p16INK4 exon 1, however, was
      demonstrated in 13 of the 26 (50%) GCTs analyzed. Tumor samples having exon 1 of
      p16INK4 methylated expressed significantly lower levels of p16INK4 mRNA, as
      analyzed by reverse transcriptase polymerase chain reaction. These results
      suggest that p16INK4 inactivation plays a role in the genesis of GCTs.

PMID- 9284837
TI  - Recent advances in breast cancer research: from genes to management.

PMID- 9284838
TI  - The effect of thyroid hormone therapy on angiographic coronary artery disease
      progression.

PMID- 9284839
TI  - Percutaneous transluminal angioplasty in coronary-internal thoracic-subclavian
      steal syndrome.

PMID- 9284840
TI  - Public policy and coronary stenting: report of an expert panel to the cardiac
      Care Network of Ontario. Cardiac Care Network of Ontario Expert Panel on
      Intracoronary Stents.

PMID- 9284836
TI  - Effects of basic fibroblast growth factor on the differentiation, growth, and
      viability of a new human medulloblastoma cell line (UM-MB1).
AB  - We presently report the effects of human recombinant basic fibroblast growth
      factor (bFGF) on a newly established medulloblastoma cell line, UM-MB1. This
      predominantly adherent cell line has a mean doubling time of 39.3 hours and was
      found, by karyotypic analysis, to be near triploid. UM-MB1 consists of
      undifferentiated cells expressing markers of neuronal lineage such as the three
      neurofilament subunits as well as neuron-specific enolase, synaptophysin, and
      microtubule-associated proteins 1 and 5. In contrast, no immunoreactivity for
      glial fibrillary acidic protein was evident. When exposed to nanomolar amounts of
      bFGF, UM-MB1 cells began to extend neurite-like processes with arborizations and
      growth-cone-like structures. In addition, UM-MB1 cells treated with bFGF
      exhibited ultrastructural alterations that reflect their enhanced differentiation
      as well as the increased expression of at least one of the neurofilament subunits
      as evidenced both immunocytochemically and on Western blots. Furthermore, bFGF
      significantly decreased UM-MB1 cell growth as well as induced their death. UM-MB1
      cells treated with bFGF for several days displayed DNA cleavage, nuclear
      shrinkage, and chromatin condensation while retaining their cytoplasmic and
      mitochondrial membrane integrity, all early indices of apoptosis. After this,
      cell death was evident with the concomitant appearance of the classical apoptotic
      bodies. By flow cytometry, bFGF was found to increase the proportion of cells in
      G1 before inducing their death by apoptosis. In conclusion, UM-MB1 cells can,
      when appropriately stimulated, be induced to differentiate along their neuronal
      lineage pathway. Their differentiation induced by bFGF, although incomplete,
      appears to promote or inhibit the expression of apoptotic effectors or
      suppressors in these cells, respectively, so to induce their death by an
      apoptotic-like mechanism.

PMID- 9284841
TI  - Appropriate hematocrit levels of erythropoietin supplementary therapy in end
      stage renal failure complicated by coronary artery disease.
AB  - OBJECTIVE: To investigate an appropriate hematocrit (Hct) for managing renal
      anemia complicated by angina pectoris at rest. DESIGN: Nonrandomized,
      retrospective and prospective observational study. SETTING: Sapporo Medical
      University Hospital, Sapporo, Japan. PATIENTS: Thirty-two anemic patients (aged
      62 +/- 10 years, range 40 to 78) with rest angina in end-stage renal failure.
      INTERVENTIONS: Serial changes of exercise tolerance (estimated metabolic
      equivalents [METs] on stress electrocardiography produced by improvement of
      patients' Hct, using recombinant human erythropoietin (rHuEPO). Adverse effects,
      such as deteriorating systemic hypertension, were investigated with regard to the
      severity of coronary arteriographic findings (Leaman's score) and cardiac events
      within a six-month period. MAIN RESULTS: Higher Hct was clearly correlated with
      better estimated METs: when Hct was less than 20%, MET was 1.4 +/- 0.5; with 20%
      < or = Hct < 25% 2.1 +/- 1.4; with 25% < or = Hct < 30% 3.1 +/- 1.6; and with 30%
      < or = Hct < 35% 4.9 +/- 1.1. Patients with cardiac events (elective balloon
      angioplasty [n = 5], bypass surgery [n = 1], myocardial infarction [n = 2] and
      hospital death from congestive heart failure [n = 3]) had advanced coronary
      lesions compared with patients without coronary events (Leaman's score 15.9 +/-
      9.3 versus 7.3 +/- 4.4, respectively, P < 0.01) and lower exercise capacity at
      25% < or = Ht < 30% (estimated METs 2.4 +/- 1.2 versus 3.9 +/- 1.9, respectively,
      P < 0.05). Moreover, there was an inverse linear correlation between estimated
      METs and Leaman's score only when Hct was over 25%. In prospectively examined
      subjects (n = 16), Hct 35% or greater without systemic hypertension was obtained
      in only seven (44%), and no additional effect on exercise tolerance was expected
      when Hct was 35% or greater. CONCLUSIONS: Managing renal anemia with 30% < or =
      Hct < 35% with rHuEPO is considered an appropriate therapy in patients with end
      stage renal failure complicated by rest angina.

PMID- 9284842
TI  - Calcium channel blockers: an evidence-based review.
AB  - Calcium channel blockers are widely used in the treatment of cardiovascular
      disease, but their proper therapeutic role is controversial. Nevertheless, drugs
      from this class have been evaluated in many controlled clinical trials of
      adequate size and duration in different patient populations. Although many
      important questions remain unanswered, these trials have clarified when and how
      these drugs should be used. In general, the benefits of calcium channel blockers
      in controlling angina and hypertension are much more clearly documented than are
      their long term effects on harder end-points such as mortality. Such long term
      data are sorely needed, particularly for hypertension. An increased risk with
      dihydropyridine calcium channel blockers has been clearly seen across several
      studies of patients with coronary disease. In coronary patients with heart
      failure, the deleterious effects of nifedipine, diltiazem and verapamil outweigh
      any possible benefit. Long acting formulations and newer calcium channel blockers
      may not share all of the adverse effects of the older drugs of this class;
      however, their long term safety has not yet been documented. An understanding of
      the limitations of calcium channel blockers, based upon clinical trial evidence,
      often leads the practitioner to choose a drug from another class, where efficacy
      has been clearly proven.

PMID- 9284843
TI  - Cardiac metastasis from primary cervical squamous cell carcinoma: three case
      reports and a review of the literature.
AB  - Clinically evident cardiac metastases from malignant neoplasms are uncommon,
      occurring most commonly in association with lung and breast carcinoma, lymphoma,
      leukemia and melanoma. The vast majority, over 90%, present with pericardial
      involvement. Squamous cell carcinomas of the cervix rarely produce cardiac
      metastases, with endomyocardia metastases being particularly rare. Three patients
      are reported who presented with primary squamous cell carcinoma of the cervix and
      developed this pattern of metastasis, one of whom was diagnosed at endomyocardial
      biopsy and the other two at autopsy. The paucity of such cases in the literature
      emphasizes the uniqueness of this phenomenon.

PMID- 9284844
TI  - Papillary fibroelastoma of the tricuspid valve.
AB  - A 50-year-old woman with a long-standing history of palpitations was found by
      echocardiography to have a 1.5 cm mass on the atrial surface of the anterior
      leaflet of the tricuspid valve. Surgical excision included a portion of
      surrounding leaflet tissue. The tumour was a papillary fibroelastoma. She
      remained asymptomatic with no recurrence in follow-up.

PMID- 9284845
TI  - Intravenous immunoglobulin, blood viscosity and myocardial infarction.
AB  - Polyvalent intravenous immunoglobulin (IVIg) is considered to be standard therapy
      for a variety of autoimmune and idiopathic disorders. Several reports have
      emphasized the temporal association between administration of IVIg and thrombotic
      events. Recent experience with a patient who suffered a large myocardial
      infarction shortly after receiving IVIg led the authors to review the clinical
      and basic literature on administration of IVIg as a possible precipitant for
      myocardial infarction. Although the existence of an association between IVIg
      administration and myocardial ischemia has not been demonstrated in clinical
      trials, a body of clinical experience has begun to accumulate that is suggestive
      of an association between IVIg administration and cardiac and cerebral ischemia
      in older individuals or individuals with a known history of ischemic disease.
      Basic research demonstrating that IVIg administration may increase blood
      viscosity suggests that such an association is plausible.

PMID- 9284846
TI  - Effect of angiotensin-converting enzyme inhibitor therapy in mitral regurgitation
      with normal left ventricular function.

PMID- 9284847
TI  - Aging effects on the organic base transporter and stereoselective renal
      clearance.
AB  - OBJECTIVE: The organic base transporter is responsible for stereoselective renal
      excretion. Changes in activity of this system secondary to aging may affect the
      disposition of an organic base in a stereoselective manner. METHODS: Eight young
      men (age range, 22 to 33 years) and seven elderly men (age range, 62 to 79 years)
      were given 10 mg pindolol twice daily, pindolol with 200 mg trimethoprim once
      daily (a known inhibitor of organic base secretion) and pindolol with 1.5 gm
      ammonium chloride (NH4Cl) four times daily for 3 days on three occasions. On day
      4, urine and plasma were collected over 24 hours to determine renal clearance
      (CLR) values of pindolol isomers. RESULTS: R(+)-Pindolol CLR values in young
      versus elderly men were 203 +/- 82 versus 150 +/- 87 ml/min, 128 +/- 51 versus
      113 +/- 35 ml/min, and 480 +/- 248 versus 247 +/- 59 ml/min during the control,
      trimethoprim, and NH4Cl study phases, respectively. S(-)-Pindolol CLR values in
      young versus elderly were 279 +/- 81 versus 207 +/- 105 ml/min, 178 +/- 70 versus
      136 +/- 42 ml/min, and 593 +/- 294 versus 276 +/- 49 ml/min during control,
      trimethoprim, and NH4Cl phases, respectively. NH4Cl increased R(+)-pindolol CLR
      by 138% (p < 0.05 versus pindolol alone) in young men, which was significantly
      greater than that observed in elderly subjects (66%; p < 0.05 versus pindolol
      alone; p = 0.016 young versus old). NH4Cl affected S(-)-pindolol CLR in a similar
      manner. Trimethoprim decreased R(+)-pindolol CLR in the young subjects by 37% (p
      < 0.05 versus pindolol alone), which was similar to that observed in the elderly
      subjects (26%; p < 0.05 versus pindolol alone; p = 0.94 young versus elderly).
      Trimethoprim affected S(-)-pindolol CLR in a similar manner. Stereoselective
      renal excretion of pindolol was unaffected by NH4Cl and trimethoprim, where the
      R(+)/S(-)-pindolol CLR ratio was unchanged (p = NS) from control in the young and
      elderly subjects. Comparison of the pindolol CLR isomer ratio between young and
      elderly groups showed no significant differences. Changes in pindolol clearance
      values resulted in significant changes in beta-blocking activity, assessed by
      isoproterenol (INN, isoprenaline) testing. CONCLUSIONS: Trimethoprim and NH4Cl
      significantly affect pindolol renal and total clearance values. Aging does not
      alter renal excretion of pindolol except for the magnitude by which renal
      excretion can be stimulated.

PMID- 9284848
TI  - Enantioselective hydroxylation of omeprazole catalyzed by CYP2C19 in Swedish
      white subjects.
AB  - Stereoselective disposition of omeprazole and its formed 5-hydroxy metabolite
      were studied in five poor metabolizers and five extensive metabolizers of S
      mephenytoin. After a single oral dose of omeprazole (20 mg), the plasma
      concentrations of the separate enantiomers of the parent drug and the 5-hydroxy
      metabolite were determined for 10 hours after drug intake. In poor metabolizers,
      the area under the plasma concentration versus time curve [AUC(0-8)] of (+)
      omeprazole was larger and that of the 5-hydroxy metabolite of this enantiomer was
      smaller than the AUC(0-8) values in extensive metabolizers (p < 0.001). The mean
      AUC(0-8) of the (-)-enantiomer of omeprazole was also higher in poor metabolizers
      than in extensive metabolizers, but only 3.1-fold compared with 7.5-fold for (+)
      omeprazole. The rate of formation of the hydroxy metabolite from (-)-omeprazole
      was low and not significantly different in poor and extensive metabolizers. These
      results show that (+)-omeprazole is to a major extent hydroxylated by CYP2C19.
      Also (-)-omeprazole may partly be metabolized by this enzyme but is mainly
      metabolized by another enzyme, presumably CYP3A4, to the achiral sulfone
      metabolite. The plasma concentration ratio of omeprazole to 5-hydroxyomeprazole
      obtained 3 hours after the drug intake has been used to distinguish between
      extensive and poor metabolizer phenotypes. With use of the ratio between the (+)
      enantiomers of the parent drug and the metabolite, a better discrimination
      between phenotypes was obtained. The ratio between the (-)-enantiomers also
      separated the phenotypes but was less discriminatory. For the future, measurement
      of total concentrations will suffice for phenotyping.

PMID- 9284849
TI  - Pharmacokinetics and pharmacodynamics of single oral doses of albuterol and its
      enantiomers in humans.
AB  - Albuterol (INN, salbutamol) is a beta 2-adrenergic receptor agonist widely used
      in the treatment of asthma. It is administered clinically as a racemic mixture,
      but only one enantiomer is active (eutomer) while the other (distomer) has been
      implicated in causing toxicity. This study used a chiral assay to compare the
      pharmacokinetics and pharmacodynamics of racemic albuterol with its two
      enantiomers in a three-way crossover of single oral doses in 12 healthy males.
      The bioavailability of the eutomer was less than that of the distomer after
      administration of pure enantiomers and racemate. Apart from causing a small
      increase in plasma potassium, the distomer had no effect on any pharmacodynamic
      parameter. The eutomer administered alone was significantly more potent than an
      equivalent dose given as racemate with regard to its effects on heart rate, QTc
      interval, plasma potassium levels, and plasma glucose levels. Despite this higher
      potency, the area under the plasma concentration versus time curve for eutomer
      after administration of pure eutomer was significantly lower than after
      administration of the racemate. This difference is probably the result of the
      more efficient metabolism of the eutomer in the absence of the distomer.

PMID- 9284851
TI  - Pharmacokinetics of sertindole in healthy young and elderly male and female
      subjects.
AB  - OBJECTIVE: The pharmacokinetic disposition of oral sertindole, a new selective
      antipsychotic compound, in young and elderly male and female subjects was
      investigated. STUDY DESIGN: A total of 46 subjects (12 young males, 11 elderly
      males, 11 young females, and 12 elderly females) received 4 mg/day sertindole
      (once a day; days 1 through 3) for 3 consecutive days, 8 mg/day sertindole for 3
      consecutive days (days 4 through 6), and 12 mg/day sertindole for 10 consecutive
      days (days 7 through 16). RESULTS: Age and gender did not appear to have any
      effect on the plasma binding of sertindole, despite a lower albumin concentration
      in elderly subjects. After multiple dosing of 12 mg sertindole, the mean peak
      plasma concentration (Cmax) values for young and elderly female subjects were 20%
      and 31% higher than those observed for male subjects of comparable age (p <
      0.05). The mean values for area under the plasma concentration-time curve [AUC(0
      24)] of female subjects were 29% higher than those observed in male subjects of
      similar age (p < 0.05). There were no statistically significant age-related
      differences in Cmax and AUC(0-24) (or apparent total plasma clearance), and there
      were no gender- or age-related differences for the elimination rate constant or
      values for apparent volume of distribution during the terminal elimination phase
      after the last 12 mg dose on day 16 (p > 0.05). CONCLUSIONS: There are no
      differences between young and elderly subjects in the absorption and elimination
      of sertindole. The higher Cmax and AUC values in females may be a result of a
      higher extent of absorption or a dependence of sertindole clearance on lean body
      mass.

PMID- 9284850
TI  - The effect of sertraline on the pharmacokinetics of desipramine and imipramine.
AB  - OBJECTIVE: To examine the pharmacokinetic interaction between the selective
      serotonin reuptake inhibitor sertraline and the tricyclic antidepressants
      desipramine or imipramine in 12 healthy male subjects. METHODS: Participants
      received a 50 mg single dose of either desipramine or imipramine under three
      conditions: alone, after a single 150 mg dose of sertraline, and after the eighth
      daily 150 mg dose of sertraline. Plasma samples were analyzed for desipramine or
      imipramine concentration by HPLC with electrochemical detection, and
      pharmacokinetics were determined with use of noncompartmental analysis of
      individual data. RESULTS: Multiple-dose, but not single-dose, treatment with
      sertraline significantly reduced apparent plasma clearance (CL/F) and prolonged
      the half-life of desipramine relative to baseline. These changes resulted in
      higher plasma desipramine concentrations, as indicated by a significant increase
      in maximum plasma concentration (Cmax) and area under the plasma concentration
      time curve extrapolated to infinity [AUC(0-infinity)] (22% and 54%,
      respectively). Both single- and multiple-dose treatment with sertraline
      significantly reduced the CL/F of imipramine. This effect was stronger after
      multiple predoses of sertraline, when imipramine Cmax and AUC(0-infinity) were
      increased by 39% and 68%, respectively. These treatment effects were consistent
      between individuals. CONCLUSIONS: This pharmacokinetic interaction is likely the
      result of an inhibition of CYP2D6 tricyclic metabolism by sertraline. When a
      tricyclic antidepressant, such as desipramine or imipramine, is coadministered
      with sertraline, lower dosages of the tricyclic agents may be necessary to
      prevent elevated tricyclic levels.

PMID- 9284852
TI  - In vivo drug-response measurements in target tissues by microdialysis.
AB  - To study the suitability of the microdialysis technique for the measurement of
      target tissue pharmacodynamics in humans, the model compounds theophylline,
      milrinone, and compound 48/80 were administered locally by means of reversed
      microdialysis to the interstitial space of skeletal muscle or skin in 24 healthy
      volunteers. Simultaneously, interstitial concentrations of cyclic adenosine
      monophosphate (cAMP; as an indicator of phosphodiesterase activity) were measured
      in skeletal muscle, and interstitial concentrations of histamine (as an indicator
      of mast cell release) were measured in skin. In muscle, reversed microdialysis
      with milrinone led to a dose-dependent increase in interstitial cAMP
      concentrations (n = 8), whereas no significant effect on cAMP was observed for
      theophylline versus placebo (1.63 +/- 0.53 nmol/L; n = 6), even at local
      concentrations exceeding those attained after therapeutic doses. In skin,
      reversed microdialysis with compound 48/80 increased interstitial histamine
      concentration dose dependently versus placebo (5.99 +/- 2.74 nmol/L; n = 10).
      From our experiments in human skeletal muscle and skin, we concluded that
      microdialysis was a suitable technique for the characterization of in vivo drug
      response at the relevant target site. Extension of these measurements to several
      other human tissues is readily feasible.

PMID- 9284854
TI  - Furosemide does not prevent indomethacin-induced renal side effects in preterm
      infants.
AB  - OBJECTIVE: To determine whether furosemide could prevent renal side effects of
      indomethacin (INN, indometacin) used for the pharmacologic closure of the patent
      ductus arteriosus (PDA) in preterm infants. METHODS: Thirty-six preterm infants
      with birth weights < 1750 gm affected by hemodynamically significant PDA were
      randomly assigned to one of two study groups. Group 1 consisted of 18 infants
      treated with three doses of indomethacin (0.20 mg/kg every 12 hours); each dose
      was followed by a dose of furosemide (1 mg/kg). Group 2 consisted of 18 infants
      treated only with the same doses of indomethacin. Body weight, urine output,
      glomerular filtration rate (GFR), fractional excretion of sodium (FENa+) and
      potassium (FEK+), and osmolal and free water clearance were evaluated in both
      groups before, during, and after treatment. RESULTS: The body weight trend, serum
      sodium, chloride and potassium concentrations, plasmatic and urinary osmolality
      were similar during the treatment in both the groups. A significant reduction of
      urine output (p < 0.01) was detected in group 2 but not in group 1. A significant
      increase of blood urea nitrogen and serum creatinine was detected at the end of
      treatment in group 1 compared with group 2. During the treatment, a significantly
      higher GFR (p < 0.05) was found in group 2 than in group 1. FENa+ and FEK+ were
      significantly higher (p < 0.05 and p < 0.001, respectively) in group 1 than in
      group 2 during and after the treatment. The osmolol clearance and free water
      clearance were significantly higher during and after treatment (p < 0.01 and p <
      0.001, respectively) in group 1 than in group 2. CONCLUSIONS: Our findings show
      that furosemide cannot prevent the indomethacin-induced renal failure, but it
      does not have any negative influence on its therapeutic effectiveness.

PMID- 9284853
TI  - Pharmacodynamics of subcutaneous recombinant human interleukin-10 in healthy
      volunteers.
AB  - Interleukin-10 inhibits T-lymphocyte activation and proliferation and
      lipopolysaccharide-induced monocyte production of proinflammatory cytokines.
      Fifty-four healthy volunteers received single doses of recombinant human
      interleukin-10 (1.0, 2.5, 5.0, 10, 25, or 50 micrograms/kg) or placebo by
      subcutaneous injection (randomized double-blind assignment). Clinical adverse
      events were infrequent at doses below 50 micrograms/kg (five of six subjects had
      mild flu-like syndrome). Mean serum interleukin-10 concentrations were dose
      related. The mean terminal-phase half-life ranged from 2.7 to 4.5 hours, and the
      apparent volume of distribution ranged from 0.70 to 1.35 L/kg. Hematologic
      changes included transient mild to moderate increases of neutrophil counts,
      decreases of lymphocyte counts, and a delayed decrease of platelet counts.
      Recombinant human interleukin-10 significantly suppressed production of the
      proinflammatory cytokines interleukin-1 beta and tumor necrosis factor-alpha by
      whole blood stimulated ex vivo with Escherichia coli lipopolysaccharide.

PMID- 9284855
TI  - Increased toxicity of high-dose furosemide versus low-dose dopamine in the
      treatment of refractory congestive heart failure.
AB  - OBJECTIVE: To evaluate the safety and efficacy of low-dose dopamine, high-dose
      furosemide, and their combination in the treatment of refractory congestive heart
      failure. METHODS: Twenty consecutive patients with refractory congestive heart
      failure were randomized to receive intravenous low-dose (4 micrograms/kg/min)
      dopamine combined with low-dose (80 mg/day) oral furosemide (group A; n = 7),
      intravenous low-dose dopamine with medium-dose furosemide (5 mg/kg/day through
      continuous intravenous administration; group B; n = 7), or high-dose furosemide
      (10 mg/kg/day through continuous intravenous administration; group C; n = 6).
      RESULTS: The three groups showed similar improvement in signs and symptoms of
      congestive heart failure, urinary output (2506 +/- 671 ml/24 hr, mean +/- SD) and
      weight loss (3.3 +/- 2.3 kg) after 72 hours of therapy. Mean arterial blood
      pressure (MAP) decreased by 14% +/- 8% and 15% +/- 6% in groups B and C,
      respectively, but increased by 4% +/- 15% in group A (p = 0.017). Renal function
      deteriorated significantly in groups B and C: creatinine clearance decreased by
      41% +/- 23% and 42% +/- 23%, respectively, but increased by 14% +/- 35% in group
      A (p = 0.0074). MAP decrease was positively correlated with the decrease in
      creatinine clearance (r = 0.7; p = 0.0007). Patients in group B and C had more
      hypokalemia than group A. Two patients in group C sustained acute oliguric renal
      failure and one patient in group B died suddenly while sustaining severe
      hypokalemia. CONCLUSION: Combined low-dose intravenous dopamine and oral
      furosemide have similar efficacy but induce less renal impairment and hypokalemia
      than higher doses of intravenous furosemide taken either alone or with low-dose
      dopamine. The renal impairment induced by intravenous furosemide is probably
      related to its hypotensive effect in patients with refractory congestive heart
      failure.

PMID- 9284856
TI  - Effects of troglitazone on insulin action and cardiovascular risk factors in
      patients with non-insulin-dependent diabetes.
AB  - OBJECTIVE: Insulin resistance is a potential target for pharmacologic
      intervention in non-insulin-dependent diabetes. Troglitazone is being evaluated
      as an insulin enhancer in insulin resistant states. RESEARCH DESIGN AND METHODS:
      We randomized 40 patients with non-insulin-dependent diabetes to diet plus
      placebo (n = 15) or diet plus troglitazone (n = 25; 200 mg/day) treatment for 8
      weeks. Fasting endogenous glucose production (EGP, by the stable isotope
      technique) and whole-body insulin sensitivity (by the insulin suppression test)
      were measured at baseline and on days 3, 7, 14, 28, and 56 of treatment. RESULTS:
      By day 56, fasting plasma glucose had risen from 12.0 +/- 0.9 to 12.8 +/- 1.2
      mmol/L in the placebo group and had fallen from 12.4 +/- 0.6 to 11.3 +/- 0.6
      mmol/L in the troglitazone group (p = 0.03). This was the result of small
      improvements in whole-body insulin sensitivity (steady-state plasma glucose
      during the insulin suppression test: from 11.09 +/- 1.1 to 10.3 +/- 0.8 mmol/L
      versus 13.8 +/- 1.0 to 10.0 +/- 0.9 mmol/L, placebo versus troglitazone; p =
      0.01) and EGP (from 103% +/- 3% versus 96% +/- 2% of baseline, placebo versus
      troglitazone; p = 0.09). The time course of insulin action showed an early (first
      week of treatment) decrease in EGP in the troglitazone group that was maintained
      throughout, whereas steady-state plasma glucose levels began to diverge toward
      the end of treatment. The effects of insulin on plasma free fatty acid and
      potassium concentrations were not different between placebo and troglitazone. The
      cardiovascular risk profile (heart rate; serum triglycerides; total, low-density
      lipoprotein, and high-density lipoprotein cholesterol; proinsulin; uric acid;
      plasminogen activator inhibitor-1 antigen and activity; 24-hour blood pressure
      monitoring and urinary albumin excretion) was unaltered by troglitazone
      treatment. CONCLUSIONS: Troglitazone as monotherapy for typical non-insulin
      dependent diabetes had a modest anti-hyperglycemic effect and, at the dose used
      in this study, had no effect on cardiovascular risk factors.

PMID- 9284857
TI  - Role of duration of diuretic effect in preventing sodium retention.
AB  - OBJECTIVE: To determine whether the duration of diuretic effect at the active
      nephron site enhances ability to excrete an exogenous salt load. METHODS: We
      conducted a study that involved eight patients with New York Heart Association
      class II to III congestive heart failure. In a randomized, crossover manner, each
      patient received 3.25 mg intravenous bumetanide at 0 hours and again at 6 hours
      or a loading dose of 0.5 mg bumetanide at 0 hours followed by a continuous
      infusion of 0.5 mg/hr for 6 hours. Response was followed for 12 hours; a total of
      6.5 mg of bumetanide was administered in each arm of the study. Eight hours after
      dosing began, we administered approximately 80 mEq sodium intravenously and
      examined its excretion over 4 hours. RESULTS: The percentage of the load excreted
      was 86% +/- 15% versus 29% +/- 30% for the infusion and bolus regimens,
      respectively (p = 0.0005). More bumetanide was excreted during the infusion (667
      +/- 133 micrograms versus 240 +/- 121 micrograms; p = 0.0002). During the
      infusion, however, more sodium was excreted relative to amounts of bumetanide,
      indicating that the efficiency of response was greater during the infusion, 0.10
      +/- 0.02 mEq sodium per microgram bumetanide versus 0.07 +/- 0.05 mEq for the
      bolus (p = 0.0145). CONCLUSIONS: These data support the notions that a long
      acting loop diuretic maintains its efficacy and that a longer duration of action
      facilitates excretion of a sodium load, such as that which might occur during
      dietary indiscretion.

PMID- 9284858
TI  - Using fuzzy logic to predict response to citalopram in alcohol dependence.
AB  - INTRODUCTION: The prediction of patient response to new pharmacotherapies for
      alcohol dependence has usually not been successful with standard statistical
      techniques. We hypothesized that fuzzy logic, a qualitative computational
      approach, could predict response to 40 mg/day citalopram and 40 mg/day citalopram
      with a brief psychosocial intervention in alcohol-dependent patients. METHODS:
      Two data sets were formed with patients from our studies who received 40 mg/day
      citalopram alone (n = 34) or 40 mg/day citalopram and a brief psychosocial
      intervention (n = 28). The output variable, "response," was the percentage
      decrease in alcohol intake from baseline. Input variables included age, gender,
      baseline alcohol intake, and levels of anxiety, depression, alcohol dependence,
      and alcohol-related problems. RESULTS: A fuzzy rulebase was created from the data
      of 26 randomly chosen patients who received 40 mg/day citalopram and was used to
      predict the responses of the remaining eight patients. Eight rules related
      response with depression, anxiety, alcohol dependence, alcohol-related problems,
      age, and baseline alcohol intake. The average magnitude of the error in the
      predictions (RMSE) was 2.6 with a bias (ME) of 0.6. Predicted and actual response
      correlated (r = 0.99; p < 0.001). A fuzzy rulebase was created from the data of
      28 randomly chosen patients who received 40 mg/day citalopram and a brief
      psychosocial intervention and was used to predict the responses of the remaining
      five patients. Six rules related response with age, anxiety, depression, alcohol
      dependence, and baseline alcohol intake with good predictive performance (RMSE =
      6.4; ME = -1.5; r = 0.96; p < 0.01). CONCLUSIONS: This study indicates that fuzzy
      logic modeling can predict response to pharmacotherapies for alcohol dependence.

PMID- 9284859
TI  - Anticonvulsant usage is associated with an increased risk of procarbazine
      hypersensitivity reactions in patients with brain tumors.
AB  - BACKGROUND: Procarbazine usage in brain tumors has a high incidence of
      hypersensitivity reactions compared with its use in other malignancies.
      Procarbazine oxidation to a reactive intermediate is enhanced by phenobarbital.
      Patients with primary brain tumors would have a preferential exposure to
      anticonvulsants compared to patients with other malignancies. OBJECTIVE: To
      determine whether anticonvulsant exposure is associated with procarbazine
      hypersensitivity reactions in patients with primary brain tumors. METHODS: This
      retrospective cohort study included 83 patients with primary brain tumors who
      were treated with procarbazine between 1981 and 1996 at a university hospital
      based regional oncology center. Data were extracted by chart review. The data
      collected included age, sex, race, tumor type, smoking, alcohol usage, and all
      concomitant medications, as well as creatinine, aspartate aminotransferase, total
      bilirubin, and anticonvulsant serum levels. Anticonvulsant exposure was
      determined by the presence of detectable serum levels. Cases of procarbazine
      hypersensitivity reactions were identified through a review of progress notes.
      RESULTS: There were 20 patients with procarbazine hypersensitivity reactions. A
      significant association between the exposure to anticonvulsants and the
      development of procarbazine hypersensitivity reactions was found (p = 0.05). In
      addition, there was a significant dose-response association between the
      development of procarbazine hypersensitivity and the presence of therapeutic
      anticonvulsant serum levels (p = 0.03). CONCLUSIONS: Concomitant exposure to
      anticonvulsants is associated with procarbazine hypersensitivity reactions,
      possibly though a reactive intermediate generated by CYP3A isoform induction. All
      patients in this cohort received enzyme-inducing anticonvulsants. New
      anticonvulsants devoid of this property are available. These data support trials
      that use these newer agents for the prophylaxis of seizures in patients with
      brain tumors who are to receive procarbazine.

PMID- 9284860
TI  - Attention deficit hyperactivity disorder (ADHD) is associated with early onset
      substance use disorders.
AB  - We evaluated the association between attention deficit hyperactivity disorder
      (ADHD) and the age of onset of psychoactive substance use disorders (PSUD) in
      adults with ADHD. We hypothesized that ADHD and psychiatric comorbidity would be
      risk factors for early onset PSUD. We compared 120 referred adults having a
      clinical diagnosis of childhood-onset ADHD with 268 non-ADHD adults. All
      diagnoses were obtained using DSM-III-R based structured psychiatric interviews.
      We used group comparisons of age at onset and Cox proportional hazard models to
      examine the development of PSUD over time. ADHD was associated with earlier onset
      of PSUD independently of psychiatric comorbidity. Conduct and juvenile bipolar
      disorders conferred a significantly increased risk for early onset PSUD
      independently of ADHD. Psychiatric disorders commonly emerged before the onset of
      PSUD in both groups. Persistent ADHD with and without psychiatric comorbidity was
      associated with adolescent onset PSUD. In addition, comorbidity with conduct and
      juvenile bipolar disorders predicted very early onset PSUD in both ADHD and non
      ADHD individuals. These findings confirm and extend previous findings documenting
      important associations between PSUD and psychiatric comorbidity including
      persistent ADHD.

PMID- 9284862
TI  - Development and validation of a measure of adolescent dissociation: the
      Adolescent Dissociative Experiences Scale.
AB  - This study describes the initial reliability and validity data on the Adolescent
      Dissociative Experiences Scale (A-DES), a screening measure for pathological
      dissociation during adolescence. The A-DES showed good scale and subscale
      reliability, and, as hypothesized, increased scores were associated with reported
      trauma in a patient population. A-DES scores were able to distinguish
      dissociative disordered adolescents from a normal sample and from a patient
      sample with a variety of diagnoses.

PMID- 9284861
TI  - Impact of comorbid personality disorders and personality disorder symptoms on
      outcomes of behavioral treatment for cocaine dependence.
AB  - Studies have revealed a significant adverse impact of comorbid personality
      disorders on treatment tenure and outcome in a variety of psychiatric and
      substance abuse populations. We investigated whether this negative relationship
      also exists among 137 urban, poor, cocaine abusers in behaviorally oriented
      treatment. Axis II diagnoses were generated categorically using the SCID-II as
      well as dimensionally using numbers of SCID-II symptoms within diagnostic
      categories. Contrary to expectations, there were no significant differences
      between subjects with and without various categorical personality disorders on
      any outcome measures. Categorical Axis II diagnoses were also minimally
      correlated with drug use severity, depression, and anxiety at intake, indicating
      that these were not potential coveriates of outcome. However, dimensional
      analyses of personality symptoms generated from the SCID-II accounted for
      substantial proportions of variance in treatment outcomes. Implications of these
      data for Axis II assessment and drug treatment planning are discussed.

PMID- 9284863
TI  - Risk factors for posttraumatic stress symptomatology in police officers: a
      prospective analysis.
AB  - This study examines internal and external risk factors for posttraumatic stress
      symptoms in 262 traumatized police officers. Results show that 7% of the entire
      sample had PTSD, as established by means of a structured interview; 34% had
      posttraumatic stress symptoms or subthreshold PTSD. Trauma severity was the only
      predictor of posttraumatic stress symptoms identified at both 3 and 12 months
      posttrauma. At 3 months posttrauma, symptomatology was further predicted by
      introversion, difficulty in expressing feelings, emotional exhaustion at time of
      trauma, insufficient time allowed by employer for coming to terms with the
      trauma, dissatisfaction with organizational support, and insecure job future. At
      12 months posttrauma, posttraumatic stress symptoms were further predicted by
      lack of hobbies, acute hyperarousal, subsequent traumatic events, job
      dissatisfaction, brooding over work, and lack of social interaction support in
      the private sphere. Implications of the findings regarding organizational risk
      factors are discussed in the light of possible occupational health interventions.

PMID- 9284864
TI  - A comparison of the symptoms associated with early and late onset alcohol
      dependence.
AB  - This study was designed to determine whether the prevalences of the DSM-III
      alcohol abuse/dependence symptoms in 87 early and 73 late onset male alcoholics
      differ from one another. The authors administered a 19-item alcohol
      abuse/dependence symptom checklist with items based on the DSM-III criteria. Nine
      of the 19 symptoms were reported significantly more often in the early than in
      the late onset alcoholics. Antisocial behaviors were reported to have been
      particularly frequent in the early onset group.

PMID- 9284865
TI  - A meta-analysis of the treatment of panic disorder with or without agoraphobia: a
      comparison of psychopharmacological, cognitive-behavioral, and combination
      treatments.
AB  - To compare short-term efficacy of benzodiazepines, antidepressants, psychological
      panic management, exposure in vivo, and combination treatments in panic disorder
      with or without agoraphobia (PA), a meta-analysis was conducted. Included were
      106 studies, pertaining to 222 treatment conditions, 5,011 patients at pretest
      and 4,016 at posttest. Pre/post effect sizes Cohen's d were calculated within the
      treatment conditions for four clinical variables: panic, agoraphobia, depression,
      and general anxiety. Seven large treatment conditions were used in the main
      analyses: high-potency benzodiazepines, antidepressants, psychological panic
      management, exposure in vivo, pill-placebo combined with exposure,
      antidepressants combined with exposure, and psychological panic management
      combined with exposure in vivo. First, these treatments were compared with a
      control condition, consisting of pill-placebo, attention placebo, and waiting
      list. Next, a comparison was made between the treatments. Antidepressants,
      psychological panic management, high-potency benzodiazepines, and antidepressants
      combined with exposure in vivo were superior to the control condition for panic
      attacks. Exposure in vivo alone was not effective for panic attacks. With regard
      to agoraphobic avoidance, all seven treatments were superior to the control
      condition. When comparing the various treatment conditions, no differences
      concerning panic attacks were found. For agoraphobic avoidance, the combination
      of antidepressants with exposure in vivo was superior to the other conditions.
      The combination of antidepressants with exposure in vivo is the most potent short
      term treatment of PA.

PMID- 9284867
TI  - Acute psychiatric responses to the explosion at the World Trade Center: a case
      series.

PMID- 9284868
TI  - Physical and sexual abuse during childhood and development of psychiatric
      illnesses during adulthood.

PMID- 9284866
TI  - Predictors of remission in patients with panic with and without agoraphobia:
      prospective 5-year follow-up data.

PMID- 9284869
TI  - Growing a healthy food system. Rebuilding connections between farmers and
      consumers.

PMID- 9284870
TI  - Community food systems: working toward a sustainable future.

PMID- 9284871
TI  - Association of cancer prevention-related nutrition knowledge, beliefs, and
      attitudes to cancer prevention dietary behavior.
AB  - OBJECTIVE: To examine the relationship of cancer prevention-related nutrition
      knowledge, beliefs, and attitudes to cancer prevention dietary behavior.
      SUBJECTS/SETTING: Noninstitutionalized US adults aged 18 years and older.
      METHODS: Data collected in the 1992 National Health Interview Survey Cancer
      Epidemiology Supplement were analyzed. The supplement included questions to
      ascertain knowledge, beliefs, and attitudes and a food frequency questionnaire to
      ascertain nutrient intake. STATISTICS: Multivariate linear regression modeling
      was conducted to assess the hypothesized relationships. RESULTS: After adjustment
      for relevant covariates (age, sex, education, total energy, perceived barriers to
      eating a more healthful diet), knowledge and belief constructs were predictive of
      dietary behavior. Specifically, fat, fiber, and fruit and vegetable intakes more
      closely approximated dietary recommendations for persons with more cancer
      prevention knowledge. The strength of the associations between these constructs
      and dietary behavior varied in some cases according to level of education and
      perceived barriers to eating a healthful diet. Of the perceived barriers to
      eating a healthful diet, perceived ease of eating a healthful diet was most
      strongly and consistently predictive of intake. CONCLUSIONS: Research findings
      challenge dietetics practitioners to design diet- and health-promotion programs
      and activities that not only educate the public about the importance of diet to
      health, but also address barriers to dietary change.

PMID- 9284872
TI  - Total energy expenditure in adults with cerebral palsy as assessed by doubly
      labeled water.
AB  - OBJECTIVES: To characterize total energy expenditure (TEE) in free-living adults
      with cerebral palsy (CP) using the doubly labeled water technique, and to
      determine those physiologic variables and characteristics of CP that were markers
      of TEE in adults with CP. DESIGN: TEE was measured using the doubly labeled water
      technique in 30 free-living adults with CP (12 women, 18 men). To determine the
      best markers of TEE, the following factors were examined: CP status, resting
      metabolic rate (RMR), anthropometric characteristics and body composition by
      means of dual-energy x-ray absorptiometry (DXA) and skinfold thickness
      measurements, energy cost of leisure-time activities, and oral-motor impairment.
      STATISTICAL ANALYSIS: Means +/- standard deviations, t tests, Pearson product
      moment correlation coefficients, Spearman rank correlation coefficients, chi 2,
      stepwise multiple-correlation regression analysis, and analysis of covariance
      were used to examine the relationships among variables of interest. RESULTS: TEE
      was highly variable in the sample (mean = 2,455 +/- 622 kcal/day for men and
      1,986 +/- 363 kcal/day for women). Stepwise regression analysis showed that TEE
      was best predicted in the sample by RMR, percentage body fat determined by DXA,
      ambulation status, and sex (multiple R = .68, P = .003). When practical, easily
      measured variables were used, TEE was best predicted by height, ambulation
      status, percentage body fat by skinfold thickness measurements, and sex (multiple
      R = .61, P. = 018). The contribution of energy expended in physical activity to
      TEE was significantly higher in the ambulatory subjects than the nonambulatory
      subjects (25% vs 16%, respectively; P = .009). APPLICATIONS: The high degree of
      variability in TEE, largely attributable to high interindividual variation in
      energy expended in physical activity, makes it difficult to provide general
      guidelines for energy requirements for adults with CP. Because ambulation status
      was an important predictor of TEE, it must be accounted for in estimating energy
      requirements in this population.

PMID- 9284873
TI  - Rethinking postoperative diets for short-stay orthopedic surgery patients.
AB  - OBJECTIVE: To examine postoperative meal tolerance and meal preferences of short
      stay orthopedic surgery patients. DESIGN: A patient survey was designed with
      input of nurses and former patients. Patient interviews focused on the first two
      meal trays provided, fluids offered, and perceived hunger after surgery.
      SUBJECTS/SETTING: Subjects (n = 31) were adult orthopedic inpatients who were
      within 24 hours of surgery conducted while they were under general anesthetic and
      who had received at least one postoperative meal tray. STATISTICAL ANALYSES
      PERFORMED: Descriptive statistical procedures were performed and chi 2 tests were
      used to compare responses at the first and second meals. RESULTS: At the first
      meal after surgery, most patients reported adverse postoperative symptoms. Twenty
      six (84%) patients had received regular meals. Fifteen (48%) patients reported
      eating almost nothing, yet 12 (39%) reported eating most or all food provided.
      Twenty-six (84%) patients thought a meal consisting of a combination of fluid and
      solid items would have been acceptable. At the second postoperative meal, fewer
      adverse symptoms were reported. Accordingly, most patients were able to eat the
      regular meal and considered solid food appropriate. Twenty-nine (94%) patients
      thought the amount of fluid provided after surgery was adequate. Eight (26%)
      patients reported feeling unreasonably hungry at some point after surgery.
      APPLICATIONS/CONCLUSIONS: Short-stay orthopedic surgery patients recover quickly
      from general anesthesia; however, patients vary in postoperative symptoms, meal
      tolerance, and meal preferences. Findings from this survey were applied to the
      development of a postoperative meal protocol, now in use, that features meals
      containing a combination of solid and fluid items.

PMID- 9284874
TI  - Relationship of nutritional status to length of stay, hospital costs, and
      discharge status of patients hospitalized in the medicine service.
AB  - OBJECTIVE: This study was conducted to determine the relationship, if any,
      between nutritional status, length of stay (LOS) in hospital, discharge
      placement, readmission rates, and hospital costs and charges in patients
      hospitalized in the medicine service. DESIGN: Data regarding medical diagnosis,
      LOS, hospital costs, charges, discharge destination, and readmission rates were
      collected prospectively from medical records and through patient interviews on
      patients admitted to the medical service who were classified to be at risk or not
      at risk for malnutrition on the basis of established criteria (weight for height
      < 75% ideal body weight, admission serum albumin level < 30 g/L, or > or = 10%
      unintentional weight loss within 1 month before admission). SUBJECTS: All
      patients admitted directly to any of three medicine units during December 1994
      who met study criteria were included in the study. Off-service patients, transfer
      patients, and patients discharged before screening (usually admitted and
      discharged within 72 hours) were excluded. Data were collected on 173 patients.
      STATISTICAL ANALYSIS PERFORMED: At-risk and not at-risk patients were compared
      for LOS, costs and reimbursement, and discharge placement (to home, to home with
      home health care services, or to another facility for further care). Two sample t
      tests and alpha survival analysis technique were used to compare continuous
      variables between the two study cohorts. Nonparametric tests were used for LOS
      and readmission data. chi 2 Tests were used for categoric variables. An alpha
      level of .05 was used throughout to determine statistical significance. RESULTS:
      Median LOS in the not-at-risk population (n = 56) was significantly greater than
      in the not-at-risk population (n = 117): 6 days (25th percentile = 4 days, 75th
      percentile = 8 days) vs 4 days (25th percentile = 3 days, 75th percentile = 7
      days) (P < .01). Mean hospitalization cost per patient was also higher in the at
      risk group ($6,196 vs $4,563, P < .02). Readmission rate per month of follow-up
      was not significantly different. At-risk patients were significantly less likely
      to be discharged home with self-care (23[41%] vs 77 [66%], P < .05). At-risk
      patients were significantly more likely to use home health care service than not
      at-risk patients (17[31%] vs 14 or [12%], P < .001). APPLICATIONS: Patients at
      risk for malnutrition had significantly higher LOS, costs, and home health care
      needs, despite the fact that 51, or 91%, received nutrition intervention while
      hospitalized. Further research should explore the use of nutrition screening and
      intervention before, during, and after hospitalization to ensure that appropriate
      nutrition intervention, as indicated by medical patients' clinical condition and
      nutritional risk status, is initiated and continued.

PMID- 9284875
TI  - Body fat percentage of children varies according to their diet composition.
AB  - OBJECTIVE: To ascertain the association between diet composition and body fat
      percentage in 9- and 10-year-old children. Also, to examine the influence of
      gender, total energy intake, fitness, physical activity, and parental body mass
      on the relationship between diet composition and adiposity. DESIGN: Diet
      composition was assessed using the National Cancer Institute food frequency
      questionnaire, and adiposity was measured using the average of results determined
      using two skinfold equations. Fitness levels and physical activity were
      ascertained using the 1-mile run/walk test and a self-report 15-item scale,
      respectively. SUBJECTS: A sample of 262 children (162 boys and 100 girls, mean
      age = 9.8 +/- 0.5 years) participated. STATISTICAL ANALYSIS: Regression analysis
      was used to determine the extent to which diet composition contributed to
      adiposity without statistical control for any potentially confounding variables.
      Partial correlations were calculated to assess the relationship between
      macronutrient intake and adiposity after potential confounders (gender, total
      energy intake, physical fitness, and parental body mass) were controlled
      statistically. RESULTS: Energy intake was positively related to adiposity. Fat
      intake, calculated as a percentage of total energy, was also positively related
      to adiposity, before and after control for potential confounding variables.
      Percentage of energy derived from carbohydrate was inversely related to
      adiposity, before and after controlling for potential confounders. APPLICATIONS:
      These findings indicate that the macronutrient intake of children, particularly
      dietary fat and carbohydrate intake, may play a role in adiposity, independent of
      the influence of total energy intake, gender, physical fitness, and parental body
      mass index.

PMID- 9284876
TI  - Fat-gram counting and food-record rating are equally effective for evaluating
      food records in reduced-fat diets.
AB  - OBJECTIVE: To compare rates of adherence to low-fat diets using food-record
      rating and fat-gram counting, to evaluate dietary adherence using the fat-gram
      counting method, and to assess correlations between food-record rating and fat
      gram counting. DESIGN: A diet monitoring and observation study was conducted to
      compare the effectiveness of food-record rating and fat-gram counting to evaluate
      dietary adherence. Subjects were randomly assigned to the food-record rating
      group of the fat-gram counting group. Each participant was asked to complete four
      3-day food records. Food records were evaluated by food-record rating for one
      group and by fat-gram counting for the other. Each record was then scored using
      the alternate system. For a subset, manually calculated fat-gram values were
      compared for accuracy with values from the Nutrient Data Systems database.
      STATISTICAL ANALYSES PERFORMED: Mantel-Haenszel chi 2, regression, and K analyses
      were used to evaluate adherence rates and within-subject agreement between fat
      gram counting and food-record rating. SUBJECTS/SETTING: Seventy-eight
      participants were recruited from a lipid-lowering research trial conducted in
      Houston, Tex. RESULTS: Strong correlations were found between fat-gram values
      calculated manually and those calculated using the Nutrient Data Systems. No
      significant differences in adherence rates were found between the food-record
      rating and fat-gram counting groups. CONCLUSIONS: Fat-gram counting is at least
      as effective as food-record rating in monitoring dietary fat content. Dietitians
      can use it as an alternative dietary fat-monitoring procedure for clinical
      practice and research.

PMID- 9284878
TI  - Dietetics and foodservice personnel are ready for team problem solving.
AB  - OBJECTIVE: To determine the readiness of dietetics and foodservice personnel for
      contributing to team problem solving. DESIGN: A descriptive, correlation study in
      which a five-part questionnaire was designed to collect data. SUBJECTS: Dietetics
      and foodservice personnel (n = 632) in eight hospital settings; 321 subjects
      (51%) volunteered to participate. STATISTICAL ANALYSES PERFORMED: Statistical
      data to summarize demographic information and two-way analysis of variance with a
      Scheffe post hoc analysis was used to investigate differences between dietetics
      and foodservice personnel on each of the subscales. RESULTS: In general, all
      respondents were somewhat oriented toward group problem solving and were
      confident in their problem-solving skills. Problem-solving expertise within the
      organization decreased for the respondents as the problem moved from their direct
      work areas to the organization level. Dietitians displayed higher self-efficacy
      in contributing to problem-solving teams than did foodservice personnel,
      indicating a 75% chance that they would contribute whereas all other respondents
      indicated a 50% chance of contributing. APPLICATIONS: The results of this study
      generate optimism for involving all dietetics and foodservice personnel in team
      problem solving. However, training activities are needed for both foodservice
      personnel and dietetics professionals.

PMID- 9284877
TI  - Changes in carotenoid intake in the United States: the 1987 and 1992 National
      Health Interview Surveys.
AB  - OBJECTIVES: To assess the changes in carotenoid intake between 1987 and 1992
      among US adults by sociodemographic characteristics and high-risk groups for
      chronic disease; and to identify the dietary sources of specific carotenoid
      intake. DESIGN: A food frequency questionnaire (FFQ) was collected from a
      representative sample of respondents to the 1987 and 1992 National Health
      Interview Surveys throughout two calendar quarters. Black and white adults, 18 to
      69 years old, participated in 1987 (n = 8,161) and 1992 (n = 8,341). METHOD: FFQ
      data were matched and linked to the US Department of Agriculture-National Cancer
      Institute carotenoid food composition database for analysis. STATISTICAL
      ANALYSIS: Mean differences in carotenoid intake over time were compared by
      sociodemographic characteristics and region of the country, after adjustment for
      sampling weights in a multiple linear regression model. RESULTS: Mean intake of
      the carotenoid lutein declined among white women (18%), among adults aged 40 to
      69 years (16%), among persons with 9 to 12 years of education (11%), among
      nondrinkers (18%), among drinkers of 1 to 6 alcoholic drinks/ week (7%), among
      smokers (former smokers by 11%, current smokers by 7%, and never smokers by 9%),
      among income groups (< $20,000 by 7%, > or = $20,000 by 9%), and residents in the
      south and northeast (by 13% each, respectively). Mean intake of the carotenoid
      lycopene increased among white men (9%), among adults aged 18 to 39 years and
      aged 40 to 69 years (by 5% and 6%, respectively), among those with 13 years of
      education or more (12.5%), among alcohol drinkers (by 10% and 7% for 1 to 6 vs 7
      or more drinks/week, respectively), among former and current smokers (by 6%
      each), among those with incomes > or = $20,000 (8%), and among residents in the
      west (16%) and midwest (5%). All differences described were statistically
      significant (P < .01). APPLICATION: The decline in lutein intake (from dark green
      leafy vegetables), particularly in white women, may have public health
      implications as a result of the recognized inverse association between carotenoid
      intake and disease risk.

PMID- 9284879
TI  - Clinical pathways in home nutrition support.
AB  - In home-care settings, physicians with various medical specialties may order home
      enteral and/or parenteral nutrition support. Clinical pathways may be used to
      provide a clear, concise, standardized method for ordering and monitoring home
      nutrition support. The clinical pathways should be appropriate for 80% of the
      patients placed on the pathways, allowing for a 20% variance, or deviation, from
      the pathway. In one home-care facility, disease-specific clinical pathways have
      been used for longer than 1 year for patients with a variety of diseases
      requiring home nutrition support. To determine the usefulness of the home
      nutrition support clinical pathways, data obtained from 20 patients were
      analyzed. Patients were followed up while being treated using home nutrition
      support clinical pathways designed for oncology (9 patients), human
      immunodeficiency virus/acquired immunodeficiency syndrome (2 patients), short
      bowel syndrome (6 patients), and hyperemesis (3 patients) for 191 weeks. Overall,
      an average variance (deviation from the pathway) of 22% (the number of variances
      divided by the total weeks of therapy) was observed. The use of the pathways to
      provide enteral or parenteral nutrition facilitated more cost-effective care by
      following pathway guidelines for obtaining laboratory values and patient visits.
      Communication between the home-care staff and the physician was also improved.
      Clinical pathways can enable standardization of care for patients receiving
      nutrition support at home.

PMID- 9284880
TI  - Pricing strategy to promote fruit and vegetable purchase in high school
      cafeterias.

PMID- 9284881
TI  - Intakes of nutrients and foods relevant to bone health in ethnically diverse
      youths.

PMID- 9284882
TI  - Troglitazone (CS-045) ameliorates albuminuria in streptozotocin-induced diabetic
      rats.
AB  - We studied the effect of troglitazone, a new oral antidiabetic agent that
      potentiates insulin action and reduces insulin resistance, on albuminuria in
      streptozotocin (STZ)-treated diabetic rats. Without affecting blood glucose
      level, blood pressure, and creatinine clearance, troglitazone treatment of
      diabetic rats significantly decreased the diabetes-associated albuminuria at all
      time points studied 14 to 12 weeks of treatment: diabetic 510 +/- 161
      micrograms/24 h v diabetic treated 112 +/- 34 micrograms/24 h at 12 weeks, P <
      .05). These data suggest that troglitazone has potential in the treatment of
      diabetic nephropathy.

PMID- 9284883
TI  - Respiratory chain activity and mitochondrial DNA content of nonpurified and
      purified pancreatic islet cells.
AB  - Considerable interest has recently focused on the possible role of alterations in
      mitochondrial activity and mutations in the mitochondrial genome for the
      development of non-insulin-dependent diabetes. Our study aimed at investigating
      the normal mitochondrial respiratory chain activity of nonpurified and purified
      islet cells to further explore whether some diabetic states are associated with
      alterations of mitochondrial oxidative processes. For this purpose, pancreatic
      islets were isolated from Wistar rats. Unpurified islet cells were obtained in
      the presence of trypsin and DNAse, and purified beta and non-beta cells were
      prepared by autofluorescence-activated sorting using a flowcytometer. Intact cell
      respiration and substrate oxidation in digitonin-permeabilized cells were
      measured polarographically with a Clark oxygen electrode in a micro-water
      jacketed cell. Specific activity of the individual complexes of the respiratory
      chain was determined spectrophotometrically in unpurified islet cells. The
      relative amount of mitochondrial (mtDNA) and nuclear (nDNA) DNA in all three cell
      populations and in rat brain and skeletal muscle was estimated by dot blotting.
      The intact cell respiration of unpurified islet cells corresponds to the mean of
      values obtained for beta and non-beta islet cells. Oxidation rates of different
      substrates by permeabilized beta cells were lower than those for unpurified and
      non-beta cells. The amount of mtDNA relative to nDNA was similar in all three
      groups of cells, and was also similar to that obtained from brain and skeletal
      muscle. In summary, we have described mitochondrial respiratory chain activity in
      unpurified, beta, and non-beta islet cells. Our results represent an initial step
      in investigating the potential pathogenic role that alterations in oxidative
      phosphorylation could play in some diabetic states.

PMID- 9284884
TI  - Quantitative genetics of serum sex hormone-binding globulin levels in
      participants in the San Antonio Family Heart Study.
AB  - Sex hormone-binding globulin (SHBG) is a steroid-binding plasma protein with a
      high affinity for testosterone that has been inversely associated with
      cardiovascular disease risk in many populations. SHBG may also act as a receptor
      in some tissues. Although the function of SHBG is relatively well understood,
      comparatively little is known about genetic factors contributing to the normal
      variation of serum SHBG levels. We estimated the heritability (h2) of serum SHBG
      levels in 717 related Mexican-Americans participating in the San Antonio Family
      Heart Study (SAFHS). We found a significant heritability (h2 = 0.31, P < .0001)
      for serum SHBG levels; age, exogenous hormones, smoking status, diabetic status,
      and adiposity showed significant associations (P < .05) with mean levels of SHBG.
      Sex was associated with mean SHBG levels but not with genetic or environmental
      variance in SHBG levels; heritability estimates were the same for males and
      females. These results indicate a significant genetic influence on SHBG in
      Mexican-Americans. Thus, SHBG may prove to be an important indicator of genetic
      risk for cardiovascular disease in this population, as well as others.

PMID- 9284885
TI  - Effects of short-term stanozolol administration on serum lipoproteins in hepatic
      lipase deficiency.
AB  - We have identified a kindred in Providence, RI, deficient in hepatic triglyceride
      lipase (HL). The two affected brothers have coronary heart disease and elevated
      levels of triglycerides, total cholesterol, high-density lipoprotein (HDL)
      cholesterol, and apolipoprotein [apo] A-I. The lipoprotein lipase (LPL) activity
      is normal. We and others have postulated that the effects of oral anabolic
      steroids on HDL metabolism are mediated by HL. To test this hypothesis, we
      treated these two men and two controls with the oral androgen stanozolol (6 mg/d)
      for 2 weeks. Consistent with other reports, HL activity increased a mean of 277%
      in controls with a concomitant decrease in HDL cholesterol (49%), HDL2
      cholesterol (90%), HDL3 cholesterol (16%), and apo A-I (41%) and no change in apo
      A-II. Although stanozolol failed to induce HL activity in the HL-deficient man,
      HDL cholesterol, HDL2 cholesterol, and apo A-I were reduced a mean of 20%, 48%,
      and 32%, respectively. In contrast to controls, HDL3 cholesterol (46%) and apo A
      II (14%) increased in HL-deficient subjects. Stanozolol treatment also increased
      LPL activity (124% +/- 86%, n = 4) and decreased lipoprotein(a) ([Lp(a)] 66% +/-
      3%, n = 3) in the three men with detectable levels. The data indicate that in
      addition to stimulation of HL activity, stanozolol treatment changes HDL
      cholesterol concentration and subfraction distribution by other mechanisms.

PMID- 9284886
TI  - Effect of glucocorticoid receptor antagonist RU 38486 on acute glucocorticoid
      induced insulin resistance in rat adipocytes.
AB  - We examined the mechanism of acute glucocorticoid-induced insulin resistance in
      rat adipocytes using the glucocorticoid receptor antagonist RU 38486.
      Pretreatment with dexamethasone (DEX) and prednisolone for 60 minutes resulted in
      50% inhibition of insulin-induced [3H]2-deoxyglucose (DOG) uptake at 10(-8) and
      10(-7) mol/L, respectively, in rat adipocytes and 20% and 25% inhibition of
      insulin-induced [3H]2-DOG uptake, respectively, in soleus muscles. Our previous
      experiments indicated that DEX and prednisolone alone stimulate protein kinase C
      (PKC) in rat adipocytes. Accordingly, we examined [3H]DEX binding to PKC from
      MonoQ column-purified rat brain cytosol. Specific [3H]DEX binding to MonoQ column
      purified PKC was observed (kd, 56.8 nmol/L; Bmax, 725 fmol/mg protein). Thus,
      insulin-induced PKC translocation from the cytosol to the membrane was suppressed
      by pretreatment with 10(-7) mol/L DEX and 10(-6) mol/L prednisolone for 80
      minutes. During treatment with RU 38486 for 60 minutes, there was no change in
      the glucocorticoid-induced inhibitory effect on insulin-induced [3H]2-DOG uptake
      and PKC translocation from the cytosol to the membrane. Moreover, pretreatment
      with RU 38486 for 120 minutes slightly prevented the DEX-mediated inhibition of
      insulin-induced glucose uptake. These results suggest that acute glucocorticoid
      induced insulin resistance may be mainly mediated through the other non
      glucocorticoid receptor pathway.

PMID- 9284887
TI  - Plasma somatostatin response to an oral test meal in liver transplant patients.
AB  - Ten liver transplant patients were studied in basal conditions and after
      ingestion of a standard mixed test meal. Control groups included 10 normal
      subjects, 10 patients with nonalcoholic liver cirrhosis, and seven kidney
      transplant patients. Plasma somatostatin, blood glucose, and plasma insulin, C
      peptide, and glucagon were determined before and 15, 30, 45, 60, 90, 120, and 180
      minutes after the start of the meal. In liver transplant patients, basal
      somatostatin and insulin levels were significantly lower than in cirrhotics and
      were comparable to those recorded in controls and in kidney transplant patients.
      The time course of the somatostatin secretory response after the meal was similar
      in any group, but the increase, evaluated as the incremental area above baseline,
      was significantly higher in liver transplant patients than in controls and
      cirrhotics and comparable to that recorded in kidney transplant patients. Insulin
      incremental areas were also lower than in cirrhotics and comparable to those
      recorded in controls and kidney transplant patients. The data suggest that in
      liver transplant patients an increased somatostatin response to a meal may be
      related to a relative beta-cell secretory defect, which in turn seems consequent
      to immunosuppressive treatment.

PMID- 9284889
TI  - Insulin resistance in non-obese, non-insulin-dependent diabetic patients with
      diabetic nephropathy.
AB  - To investigate the association between insulin resistance and diabetic
      nephropathy, peripheral insulin sensitivity indices (M/I values) were evaluated
      via euglycemic-hyperinsulinemic clamp in 45 non-obese, non-insulin-dependent
      diabetic (NIDDM) subjects. The patients were divided into four groups: 18 with
      normoalbuminuria (urinary albumin excretion rate [AER] < 30 mg/24 h, stage I), 10
      with microalbuminuria (30 < or = AER < or = 300 mg/24 h, stage II), seven with
      overt proteinuria (AER > 300 mg/24 h, stage III), and 10 with uremia (serum
      creatinine levels > 2.0 mg/dL, stage IV). There were no significant differences
      in age, body mass index (BMI), fasting plasma glucose, or hemoglobin A1c (HbA1c)
      among the four groups. No significant difference in M/I values was seen between
      stage I and stage II (6.30 +/- 0.73 and 5.95 +/- 0.85 mg/kg/(min per microU/mL) x
      100, respectively). M/I values in the stage I and stage II groups were strongly
      correlated with BMI (r = -.790, P = .0001 and r = -.785, P = .007, respectively).
      M/I values in the stage III group (4.53 +/- 0.51) were lower than in the stage I
      group, although not significantly so. M/I values in the stage IV group (3.16 +/-
      0.37) were significantly lower than in the stage I group (P = .025). In multiple
      regression analysis with a model in which age, sex, BMI, HbA1c, and creatinine
      clearance (Ccr) were included as independent variables, BMI and Ccr were
      demonstrated to be significant and independent contributors to insulin
      sensitivity indices as the dependent variable (beta = -0.716 and beta = 0.272,
      respectively, R2 = .564, P < .0001). In conclusion, the present cross-sectional
      study demonstrated in non-obese NIDDM patients with nephropathy that
      microalbuminuria did not affect peripheral insulin resistance, but uremia did, as
      in nondiabetic patients, and that the peripheral insulin resistance was
      significantly contributed to by the degree of obesity and uremia.

PMID- 9284888
TI  - Smokeless nicotine administration is associated with hypertension but not with a
      deterioration in glucose tolerance in rats.
AB  - Cigarette smoking is a major risk factor for coronary heart disease. To further
      investigate the relationship of nicotine with other cardiac risk factors, we
      studied the impact of nicotine on blood pressure and glucose tolerance. Adult
      male Sprague-Dawley rats were randomly assigned to receive nicotine or placebo
      pellets implanted subcutaneously. Weight gain was controlled by pair-feeding, and
      was not significantly different between nicotine- and placebo-treated animals.
      Blood pressure (in mm Hg) increased throughout a 3-week treatment period in
      nicotine-treated animals and was significantly higher [P < .05 by two-way ANOVA]
      than in placebo-treated rats. Blood pressure returned to normal within 1 week
      following exhaustion of the pellets. Oral glucose tolerance tests performed 2.5
      weeks after pellet placement showed similar glucose, insulin, and free fatty acid
      (FFA) profiles by two-way ANOVA. In summary, smokeless nicotine exposure leads to
      sustained but reversible hypertension without deterioration in glucose tolerance
      or insulin action when weight gain is controlled. We conclude that in rats
      smokeless nicotine adversely affects the coronary risk profile by increasing
      blood pressure.

PMID- 9284890
TI  - Diabetes mellitus associated with the 3243 mitochondrial tRNA(Leu)(UUR) mutation:
      insulin secretion and sensitivity.
AB  - To investigate the pathophysiology of diabetes mellitus associated with the 3243
      mitochondrial tRNA(Leu)(UUR) mutation (DM-Mt3243), insulin secretion and
      sensitivity were studied using the 75-g oral glucose tolerance test (oGTT), 1-mg
      intravenous glucagon test, and euglycemic glucose clamp test. Twelve DM-Mt3243
      patients were investigated (seven men and five women). Their ages ranged from 36
      to 74 years, and the onset of diabetes occurred at 44.5 +/- 9.5 years (mean +/-
      SD). In the glucose tolerance test, nine patients (75.0%) showed lower C-peptide
      reactivity (CPR) than normal at 30 minutes, suggesting blunted insulin secretion.
      Three patients showed an impaired glucose tolerance (IGT) pattern, although they
      had absolute hyperglycemia at the onset of diabetes. In the glucagon test, 10
      patients (76.3%) had CPR within the normal range at 6 minutes, indicating an
      adequate response. In the glucose clamp test, the M value was 8.70 +/- 2.35
      mg/kg/min and was within normal limits in all patients. The glucose metabolized
      (M value) was negatively correlated with 24-hour urinary C-peptide excretion (r =
      .696, P < .05). Thus, plasma CPR to glucose loading was blunted in many DM-Mt3243
      patients, but CPR to glucagon was relatively well preserved. This difference in
      the intrinsic insulin response to the two stimuli may be characteristic of DM
      Mt3243. Although M values were normal in all subjects, the correlation with 24
      hour urinary C-peptide excretion suggests a relationship between insulin
      sensitivity and insulin secretion. These two mechanisms may cooperate to maintain
      homeostasis in this disease. Since three patients did not progress with aging,
      this mutation may not always cause gradual beta-cell destruction.

PMID- 9284891
TI  - Guanidino compounds in serum and urine of nondialyzed patients with chronic renal
      insufficiency.
AB  - Levels of 15 guanidino compounds and urea were determined in serum and urine of
      nondialyzed patients with chronic renal insufficiency subdivided according to
      etiology and creatinine clearances. No significantly different guanidino compound
      levels in serum and urine were found for the interstitial nephritis,
      glomerulonephritis, nephrangiosclerosis, and diabetic nephropathy subgroups.
      Subdividing the patients according to creatinine clearance yields the following
      results: (1) Serum guanidinosuccinic acid (GSA) and methylguanidine levels of
      patients with end-stage renal failure (creatinine clearance < 10 mL/min) are up
      to 100 and 35 times higher than control levels, while guanidine, creatinine, and
      symmetrical dimethylarginine (SDMA) are increased about 10 times. Serum levels of
      asymmetrical dimethylarginine (ADMA) are only doubled in end-stage renal failure.
      Serum levels of guanidinoacetic acid (GAA) and homoarginine are significantly
      decreased. (2) Urinary excretion levels of most guanidino compounds decrease with
      decreasing creatinine clearance except for GSA and methylguanidine. (3) Greater
      than 90% of patients with creatinine clearance ranging from subnormal to 40
      mL/min have serum SDMA levels higher than the upper-normal limit; up to 80% have
      increased GSA levels. (4) The clearance rates of some of the guanidino compounds
      could be calculated: with the exception of arginine, they decrease with
      decreasing creatinine clearance. This study shows specific abnormal guanidino
      compound levels in serum and urine of nondialyzed patients with chronic renal
      insufficiency that can be used as complementary diagnostic parameters. The best
      correlation between serum guanidino compound levels and the degree of renal
      insufficiency is found for GSA, SDMA, methylguanidine, and guanidine. Urinary
      excretion levels of ADMA correlate best with decreasing creatinine clearance.
      Serum levels of GSA and especially SDMA are candidate indicators for the onset of
      renal failure.

PMID- 9284893
TI  - Basal growth hormone levels are positively correlated with high-density
      lipoprotein cholesterol levels in women.
AB  - Previous studies in patients with either a deficiency or an excess of growth
      hormone (GH) yielded contradictory results on the regulation of lipoprotein
      metabolism by GH. In a cross-sectional study of 563 male and 126 female
      participants of the Prospective Cardiovascular Munster (PROCAM) Study, we
      determined biometric and demographic data, serum levels of total cholesterol,
      triglycerides, high-density lipoprotein (HDL) cholesterol, low-density
      lipoprotein (LDL) cholesterol, apolipoprotein (apo)A-I, A-II, and B, and
      unstimulated GH levels. The median of basal GH levels was higher in women than in
      men. Moreover, 44.2% of men but only 8.7% of women had basal GH levels less than
      the detection limit of 0.05 microgram/L. The relationship between basal GH and
      lipoprotein metabolism was investigated by univariate and multivariate regression
      analysis of data from 315 men and 126 women with detectable basal GH levels. In
      men, GH correlated positively with HDL cholesterol and negatively with body mass
      index (BMI), age, and triglycerides. After multivariate analysis, the correlation
      with triglycerides remained independent of age and BMI. Among women, GH
      correlated positively with the use of hormonal contraception, HDL cholesterol,
      apoA-I, and apoA-II, and negatively with BMI, age, menopause, triglycerides, and
      apoB. With multivariate analysis, the positive correlations of GH with HDL
      cholesterol and apoA-I in women were independent of age. BMI, menopause, and oral
      contraception. We conclude that GH contributes to the regulation of HDL
      cholesterol levels. Moreover, in women the well-known effects of exogenous
      estrogen or estrogen loss on HDL metabolism may be partially mediated via GH.

PMID- 9284892
TI  - Renoprotective effects of a combined endothelin type A/type B receptor antagonist
      in experimental malignant hypertension.
AB  - We previously showed that plasma endothelin-1 (ET-1) concentration was increased
      in deoxycorticosterone acetate (DOCA)-salt-induced malignant hypertension in
      spontaneously hypertensive rats (SHR). In contrast, in normal SHR, this value is
      similar to that seen in Wistar-Kyoto (WKY) rats. The purpose of this study was to
      examine the effects of the new combined ET type A/type B (ETA/B) receptor
      antagonist, TAK-044, on the development of hypertension in this model of
      malignant hypertension. TAK-044 10 mg/kg, which effectively blocks both ETA and
      ETB receptors, was administered intraperitoneally once per day for 4 weeks in
      DOCA-salt SHR, and the effects on ET-1 and other parameters were compared with
      the same values in untreated WKY rats, untreated DOCA-salt SHR, and hydralazine
      treated DOCA-salt SHR. DOCA-salt caused marked increases in blood pressure, blood
      urea nitrogen (BUN), serum creatinine, and plasma ET-1 concentrations in SHR.
      Both TAK-044 and hydralazine significantly suppressed the increase in blood
      pressure in DOCA-salt SHR to the same extent. Both treatments also suppressed the
      increase in BUN and serum creatinine, but this attenuation was less marked with
      hydralazine than with TAK-044. Neither TAK-044 nor hydralazine affected plasma ET
      1 concentration in this model. TAK-044 significantly reduced kidney weight in
      DOCA-salt SHR, whereas the decrease seen with hydralazine was less marked.
      Prevention of DOCA-salt-induced renal structural injury (mesangial
      hypercellularity, glomerular sclerotic changes, and tubulointerstitial damage) in
      this model was clearly greater with TAK-044 treatment than with hydralazine
      treatment. These results suggest that endogenous ET-1 may, at least in part,
      contribute to renal functional and structural damage in malignant DOCA-salt SHR.
      Our results raise the possibility of renoprotective effects of ETA/B receptor
      blockers in certain forms of malignant hypertension.

PMID- 9284894
TI  - Expression of human islet amyloid polypeptide/amylin impairs insulin secretion in
      mouse pancreatic beta cells.
AB  - Non-insulin-dependent diabetes mellitus (NIDDM) is associated histopathologically
      with islet amyloid deposits of which a major component is islet amyloid
      polypeptide (IAPP)/amylin. We examined whether endogenous IAPP controls insulin
      secretion via a local effect within pancreatic islets and whether overexpression
      of this peptide contributes to pancreatic beta-cell dysfunction in this disease.
      Transgenic mice expressing human IAPP in pancreatic beta cell were used in this
      study. Human IAPP expression did not influence the mouse proinsulin mRNA level
      and insulin content. Glucose-induced insulin secretion was decreased in the
      isolated pancreatic islets of transgenic mice. MIN6, a glucose-responsive
      pancreatic beta-cell line, was transfected with human IAPP cDNA by a lipofectin
      method. Human IAPP expression was confirmed by RNA blot and immunohistochemical
      analysis. In two transfectants expressing the largest amount of human IAPP,
      insulin secretion was increased in response to glucose stimulation; however, the
      magnitude of the insulin response in cells transfected with human IAPP was
      smaller than in control clones. Insulin content was not influenced by the
      expression. We conclude that endogenous IAPP inhibits insulin secretion via an
      autocrine effect within pancreatic islets, and that the impaired insulin
      secretion in this disease may be partly caused by overexpression of IAPP.

PMID- 9284895
TI  - Insulin-like growth factor-I improves glucose utilization in tumor necrosis
      factor-treated rats under hyperinsulinemic-euglycemic conditions.
AB  - The purpose of this study was to determine the effects of insulin-like growth
      factor-I (IGF-I) on glucose metabolism in normal and tumor necrosis factor (TNF)
      treated rats under euglycemic and hyperinsulinemic conditions. During a
      hyperinsulinemic clamp (10 mU/kg.min), rats further received either saline or IGF
      I (3.33 micrograms/kg.min) infusion for 2 hours. Glucose kinetics were determined
      with [3H-3]-glucose. Glucose utilization in peripheral tissues was examined by
      glucose uptake using [14C-2]-deoxyglucose (14C-DG) and by glycogen content in
      select tissues. The results showed that TNF infusion significantly decreased the
      rate of glucose infusion required to maintain euglycemia. TNF decreased glycogen
      content significantly in liver and marginally in abdominis muscle. TNF also
      decreased glucose uptake in muscle, although the decrease was only statistically
      significant compared with IGF-I infusion. In addition, TNF significantly reduced
      plasma IGF-I concentration. However, during hyperinsulinemic and euglycemic
      conditions, exogenous IGF-I significantly increased glucose uptake in muscle and
      glycogen storage in the liver and abdominis muscle in both saline- and TNF
      treated groups. IGF-I normalized each of the effects of TNF in the rats,
      including those on plasma IGF-I, glucose uptake in muscle, and glycogen content
      in liver and abdominis muscle. These data suggest that under hyperinsulinemic and
      euglycemic conditions, TNF-treated rats, although resistant to insulin, have a
      normal response to IGF-I, indicating that the TNF-induced defect in the insulin
      pathway may not be a step in the IGF-I pathway.

PMID- 9284896
TI  - Body composition changes in chronic hemodialysis patients before and after
      hemodialysis as assessed by dual-energy x-ray absorptiometry.
AB  - The aim of this study was to investigate the effect of hemodialysis on body
      composition assessment by dual-energy x-ray absorptiometry (DEXA). Seventeen
      patients with chronic renal failure who were on a regular hemodialysis schedule
      were studied. Body weight and body composition were assessed immediately before
      and approximately 1 hour after a typical hemodialysis session. Body weight was
      assessed by means of an electronic balance. Body composition measurements were
      made by DEXA. Whole-body and subtotal (head and neck excluded) analysis assessed
      the following parameters: body weight, bone mineral density (BMD), bone mineral
      content (BMC), and fat (FTM) and lean (LTM) tissue mass. BMC, FTM, and LTM were
      estimated separately for the trunk, arms, and legs. The mean body weight
      reduction after hemodialysis was 2.8 +/- 1.1 kg (mean +/- SD). Concerning whole
      body analysis, no change was observed in mean BMC and FTM after hemodialysis. On
      the contrary, a significant reduction was observed in mean body weight as
      assessed by DEXA (before hemodialysis, 65.0 +/- 11.4 kg; after, 62.2 +/- 10.9 kg,
      P = .0003), as well as in mean LTM (before hemodialysis, 42.7 +/- 9.4 kg; after,
      39.7 +/- 9.0 kg, P = .0003). Similar results were obtained from subtotal and
      regional analysis. Body weight changes as measured by the electronic balance
      exhibited a strong positive correlation with the changes in both body weight and
      LTM as assessed by DEXA (r = .989, standard error of the estimate [SEE] = 0.167
      kg and r = .941, SEE = 0.382 kg, respectively, P < .0001). It is concluded that
      gravimetric changes induced by hemodialysis are highly correlated with LTM
      changes and are not associated with changes in BMC or FTM estimated by DEXA.

PMID- 9284898
TI  - L-arginine but not D-arginine stimulates insulin-mediated glucose uptake.
AB  - Our study aims at investigating a possible role for L-arginine and D-arginine in
      insulin-mediated glucose uptake. Twelve lean healthy subjects volunteered for the
      study and were submitted to three euglycemic-hyperinsulinemic glucose clamps to
      investigate the effect of L-arginine (0.5 g/min in the last 60 minutes of the
      clamp), D-arginine (0.5 g/min in the last 60 minutes of the clamp), and saline
      0.9% NaCl on insulin-mediated glucose uptake. All tests were made in random
      order. In study 1, L-arginine versus saline infusion was associated with a
      significant increase in blood flow (131% +/- 7% v 87% +/- 5%, P < .001) and whole
      body glucose disposal ([WBGD] 61.4 +/- 4.4 v 41.3 +/- 3.5 mumol/kg fat-free mss
      [FFM].min, P < .001). Analysis of substrate oxidation demonstrated that both
      oxidative and nonoxidative glucose metabolism was improved by L-arginine
      delivery. After adjustment for the change in blood flow, WBGD was still greater
      after L-arginine than after saline infusion. Along with L-arginine infusion and
      independently of the change in blood flow, the percent change in WBGD correlated
      with the percent change in plasma cGMP (r = .55, P < .05). D-Arginine infusion
      did not affect insulin-mediated glucose uptake. In particular, WBGD (42.1 +/- 3.4
      v 41.3 +/- 3.5 mumol/kg FFM.min, P = NS) was similar in both experimental
      conditions. Basal levels (2.8 +/- 0.2 v 2.7 +/- 0.3 nmol/L, P = NS) and the
      insulin-mediated increase (43% +/- 5% v 39% +/- 4%, P = NS) in plasma cGMP were
      also superimposable along with insulin plus D-arginine and insulin alone,
      respectively. Finally, blood flow (224 +/- 29 v 230 +/- 35 mL/min, P = NS) was
      not different at baseline and was similarly stimulated (84% +/- 4% v 87% +/- 5%,
      P = NS) by insulin infusion. In conclusion, L-arginine but not D-arginine
      stimulates insulin-mediated glucose uptake. Nitric oxide (NO), the metabolic
      mediator for L-arginine, potentiates insulin-mediated glucose uptake through the
      increase in blood flow. Nevertheless, an independent effect of intracellular cGMP
      on WBGD cannot be ruled out.

PMID- 9284897
TI  - Serum creatine, creatinine, and other guanidino compounds in patients with
      thyroid dysfunction.
AB  - Serum levels of creatine (CT), creatinine (CTN), urea, guanidinosuccinic acid
      (GSA), guanidinoacetic acid (GAA), guanidine (G), arginine (Arg), homoarginine
      (Harg), argininic acid (ArgA), and alpha-keto-delta-guanidinovaleric acid (alpha
      K-delta-GVA) were measured in 54 patients with hyperthyroidism, 56 with
      subclinical hyperthyroidism, 28 with subclinical hypothyroidism, and 51 with
      hypothyroidism compared with 62 euthyroid controls. In agreement with previous
      reports, serum CT increased (+35%) and CTN decreased (-17.6%) in hyperthyroidism
      as compared with normal thyroid function, whereas the opposite was seen in
      hypothyroidism (-17.7% and +11%, P < .0001). Original findings from this study
      are a highly significant decrease in GSA (-41.7%) and GAA (-36.8%) in
      hyperthyroidism and an increase in GSA (+36%) in hypothyroidism (P < .0001). In
      addition, a slight decrease in hyperthyroidism and hypothyroidism was noted for
      Arg (-6.2% and -13.2%, P = .001) and Harg (-14.8% and -18.1%, P = .05). By
      contrast, no significant change was seen in levels of urea, G, ArgA, and alpha-K
      delta-GVA. No major differences were found for any of the compounds between
      subclinical hypothyroidism, euthyroidism, and subclinical hyperthyroidism. There
      was a highly significant positive linear correlation between urea and GSA levels
      in hyperthyroidism, euthyroidism, and hypothyroidism (r = .68, r = .77, and r =
      .75, P < .0001), taking into account that for the same increase in urea, GSA
      increased threefold more in hypothyroid versus hyperthyroid patients. In
      conclusion, apart from CT and CTN, significant changes can be found in serum
      levels of GSA, GAA, Arg, and Harg in patients with thyroid dysfunction.
      Subclinical thyroid dysfunction does not seem to induce changes in serum levels
      of guanidino compounds. Decreased serum GSA and GAA levels might be an additional
      indicator of hyperthyroidism.

PMID- 9284899
TI  - Hyperinsulinemia and hypofibrinolysis: effects of short-term optimized glycemic
      control with continuous insulin infusion in type II diabetic patients.
AB  - A defect in the fibrinolytic system results from an increase in type 1
      plasminogen activator inhibitor (PAI-1) in diabetes. It can be considered an
      independent risk factor for the development of cardiovascular disease. In obese
      and type II diabetic patients, plasma PAI-1 level correlates with fasting
      insulinemia. However, during the euglycemic clamp, acute hyperinsulinemia does
      not increase PAI-1 production. The present study was undertaken to investigate
      the effect of optimized glycemic control by continuous subcutaneous insulin
      infusion (CSII) on the hypofibrinolytic state for 14 days in 16 type II diabetic
      patients with poor metabolic control despite maximal oral antidiabetic treatment.
      Plasma PAI-1 activity levels decreased from 13.38 +/- 2.85 IU/mL to 6.77 +/- 1.81
      IU/mL (P = .002) during CSII, along with a concurrent improvement in insulin
      sensitivity (index obtained by basal glycemia-nadir glycemia/basal glycemia)
      during the insulin sensitivity test (0.121 +/- 0.03 v 0.057 +/- 0.02, P = .02).
      These results suggest that insulin resistance rather than hyperinsulinism may be
      involved in the hypofibrinolytic state in type II diabetic patients. The positive
      correlation between the changes in triglycerides and in PAI-1 activity (r = .589,
      P = .026) strongly suggests a role for triglycerides in the impairment of
      fibrinolysis, which could be a link between insulin resistance and
      hypofibrinolysis.

PMID- 9284901
TI  - Relation between serum triglyceride level, serum urate concentration, and
      fractional urate excretion.
AB  - The relations between serum urate levels and age, serum cholesterol, creatinine,
      glucose, and triglyceride concentrations were studied in 930 men and 298
      premenopausal and 478 postmenopausal women, taking into account the renal
      handling of uric acid. All subjects were outpatients, and statistical evaluation
      was performed on cases corresponding to the central 95th percentile of the
      biochemical variables measured. An alternative analysis excluding subjects with
      serum glucose or creatinine levels outside the normal range was also performed.
      In men, premenopausal and postmenopausal women, and their normoglycemic
      normocreatininemic subsets, serum triglyceride level was positively correlated
      with serum urate concentration and inversely correlated with fractional urate
      excretion in both simple and multiple linear regression analysis. In men and
      postmenopausal women, there was also a strong positive independent association
      between serum urate and creatinine levels. This association was significant also
      in the normoglycemic normocreatininemic subset of men, but it was insignificant
      in normoglycemic normocreatininemic postmenopausal women. In this large cross
      sectional study, a negative correlation between serum triglyceride concentration
      and renal uric acid excretion has been demonstrated.

PMID- 9284900
TI  - Lipolytic sensitivity and response to fasting in normotensive and hypertensive
      obese humans.
AB  - Obese persons with hypertension are at greater risk for diabetes and
      hyperlipidemia than normotensive obese persons. It has been postulated that
      increased lipolytic rates contribute to these metabolic diseases. Therefore, we
      evaluated the glycerol rate of appearance (Ra) in plasma, an index of whole-body
      lipolytic activity, during basal conditions and during 60 minutes of epinephrine
      infusion after 12 and 84 hours of fasting in six normotensive (body mass index
      [BMI], 39.9 +/- 1.8 kg/m2) and six hypertensive (BMI, 38.7 +/- 1.6 kg/m2) obese
      persons. Basal glycerol Ra was lower in hypertensive than in normotensive
      subjects at both 12 hours (1.58 +/- 0.21 v 2.27 +/- 0.28 mumol/kg/min,
      respectively; P < .01) and 84 hours (2.04 +/- 0.06 v 2.50 +/- 0.13 mumol/kg/min,
      respectively; P < .01) of fasting. Peak glycerol Ra during epinephrine infusion
      after 84 hours of fasting (5.69 +/- 0.72 and 11.40 +/- 0.78 mumol/kg/min for
      hypertensive and normotensive subjects, respectively) was significantly greater
      than at 12 hours (3.09 +/- 0.29 and 5.06 +/- 0.69 mumol/kg/min) in both
      hypertensive and normotensive subjects. However, peak glycerol Ra was lower in
      hypertensive than in normotensive subjects after 12 and 84 hours of fasting (P <
      .01 for 84 hours). We conclude that hypertension in obese persons is associated
      with a decrease in both basal lipolytic rates and lipolytic sensitivity to
      epinephrine infusion.

PMID- 9284902
TI  - E64d, a membrane-permeable cysteine protease inhibitor, attenuates the effects of
      parathyroid hormone on osteoblasts in vitro.
AB  - Parathyroid hormone (PTH) activates calpains I and II (calcium-activated papain
      like proteases) and stimulates the synthesis and secretion of cathepsin B (a
      lysosomal cysteine protease) in osteoblastic cells. Anabolic doses of PTH also
      stimulate osteoprogenitor cell proliferation and differentiation into mature,
      fully functional osteoblasts capable of elaborating bone matrix, whereas
      catabolic doses of PTH stimulate calcium mobilization and matrix turnover.
      Previous investigations in other cell types have demonstrated that calcium
      activated calpains play a major role in regulating proliferation and
      differentiation by catalyzing limited regulatory proteolysis of nuclear proteins,
      transcription factors, and enzymes. We tested the hypothesis that inhibition of
      intracellular cysteine proteases such as the calpains will ablate PTH-mediated
      osteoblast proliferation and differentiation, two fundamental indices of bone
      anabolism. A brief preincubation with the membrane-permeable, irreversible
      cysteine protease inhibitor E64d (10 micrograms/mL) before short-term PTH
      treatment blunted PTH-induced cell proliferation in subconfluent cultures and
      also attenuated proliferation and inhibited differentiation in longer-term
      confluent cultures. This confirms the hypothesis that cysteine proteases such as
      the calpains are important in mediating the proliferative and prodifferentiating
      or anabolic effects of PTH on MC3T3-E1 cells in culture. Immunofluorescent
      localization demonstrated that calpain I, calpain II, and calpastatin (the
      endogenous calpain inhibitor) are abundant and widely distributed within actively
      proliferating MC3T3-E1 preosteoblasts. Since the calpains are active and stable
      at neutral intracellular pH levels in osteoblasts, whereas cathepsins are not,
      our results support a role for these calcium-activated regulatory proteases in
      mediating the anabolic effects of PTH in bone.

PMID- 9284903
TI  - Normal intestinal dietary fat and cholesterol absorption, intestinal
      apolipoprotein B (ApoB) mRNA levels, and ApoB-48 synthesis in a
      hypobetalipoproteinemic kindred without any ApoB truncation.
AB  - The purpose of this study was to characterize intestinal apolipoprotein B (apoB)
      metabolism in subjects with familial hypobetalipoproteinemia (FHBL), where
      segregation analysis supports linkage to the apoB gene but no apoB truncations
      are present. We investigated cholesterol and fat absorption, intestinal apoB mRNA
      synthesis and editing, as well as apoB-48 synthesis. Plasma triglycerides (TG)
      and retinyl palmitate in the chylomicron fractions were analyzed after 12 hours
      of fasting and then repeatedly for 14 hours after ingestion of a vitamin A
      containing high-fat meal. Cholesterol absorption was assessed using a dual stable
      isotope method. Mean peak times and concentrations and areas under the curve
      (AUCs) for fat absorption and mean percentages of cholesterol absorption were
      comparable in affected and nonaffected family members. Intestinal biopsies were
      extracted for total RNA and also incubated with 35S-methionine for measurements
      of apoB synthesis. Similar quantities of apoB mRNA were found to be expressed in
      the intestine in affected and control subjects by RNase protection assay. ApoB
      mRNA editing assay showed that the majority of apoB-100 mRNA was edited to the
      apoB-48 form to a similar extent in both groups. Virtually no apoB-100 protein
      was synthesized by the intestine in any subject, and apoB-48 protein synthesis
      was not significantly different in the affected individuals. These data are
      consistent with in vivo metabolism data that show normal production rates for
      liver-derived apoB-100 but increased apoB-100 fractional catabolic rates in
      affected members of this family. Thus, the molecular defect probably does not
      affect transcription, translation, or secretion of apoB-containing lipoproteins,
      but may instead affect their clearance.

PMID- 9284905
TI  - Assignment of COX6A1 to 6p21 and a pseudogene (COX6A1P) to 1p31.1 by in situ
      hybridization and somatic cell hybrids.

PMID- 9284904
TI  - A high-fat diet influences insulin-stimulated posttransport muscle glucose
      metabolism in rats.
AB  - Because of a failure to detect significant quantities of intracellular glucose,
      it has been generally accepted that transport rather than phosphorylation is the
      rate-limiting process of muscle glucose metabolism under most (but not all)
      physiological conditions. Here, we have measured tissue free levels of the
      glucose analog 2-deoxy-D-glucose (2DG) in red quadriceps muscle of rats fed a
      high-fat diet (59% of energy from fat) for 3 weeks, to identify the barrier to
      insulin-stimulated glucose uptake previously seen in such animals. Measurements
      were performed on pentobarbital-anesthetized rats following exogenous infusion of
      radiolabeled 2DG. A glucose clamp was used to maintain plasma insulin at high
      physiological levels (approximately 120 mU/L). Three other treatment groups
      representing normal insulin action (chow-fed), extreme glucose uptake (maximal
      insulin stimulation + hyperglycemia), and insulin resistance with elevated free
      intracellular glucose (epinephrine infusion) were also studied for comparison. In
      chow-fed animals, no muscle free 2DG was detected, confirming transport as the
      rate-limiting process. In fat-fed animals, a significant elevation in muscle free
      2DG was observed (P < .01 v chow-fed controls). The elevation was similar in
      magnitude to that in epinephrine-infused rats, and implied a limitation of
      insulin action at a posttransport step. This result was confirmed with a more
      complex modeling analysis. We conclude that posttransport steps influence insulin
      stimulated in vivo muscle glucose metabolism in long-term high-fat-fed rats.

PMID- 9284906
TI  - Human type I cytokeratin genes are a compact cluster.
AB  - A YAC clone (211F11) containing approximately 0.5 Mb of human DNA was isolated
      from a human genomic library by PCR-based screening with cytokeratin (KRT) 13
      specific primers. The YAC clone was mapped by FISH to the long arm of chromosome
      17 (17q12-->q21), a region to which several other type I KRT genes had been
      mapped previously. We now show by Southern blot hybridization and PFGE analyses
      that KRT13, 14, 15, and 16 are all contained within YAC clone 211F11. Long-range
      restriction mapping analysis of clone 211F11 and of two smaller YAC clones that
      were also isolated with KRT13-specific primers, suggests that KRT13, 14, 15, 16
      and their linked type I genes KRT17 and 19, are contained in less than 150 kb of
      genomic DNA. According to our reconstruction it then appears that at least six
      type I KRT genes are arranged in a highly compact cluster. The three YACs
      reported in this study represent a new tool to dissect the molecular structure of
      the locus of the human type I KRT genes.

PMID- 9284908
TI  - Assignment of acetyl-CoA carboxylase-beta (ACACB) to human chromosome band
      12q24.1 by in situ hybridization.

PMID- 9284907
TI  - A FISH probe specific for the telomeric region of 6p.

PMID- 9284909
TI  - Assignment of the germ cell cyritestin gene 2 (CYRN2) to human chromosome 16q12.1
      by fluorescence in situ hybridization to 5-azacytidine induced, partially
      decondensed chromosomes.

PMID- 9284910
TI  - Assignment of the mouse heme oxygenase genes: heme oxygenase-1 (Hmox1) to
      chromosome 10 band C1 and heme oxygenase-2 (Hmox2) to chromosome 16 band B1.

PMID- 9284911
TI  - Minibrain (MNBH) is a single copy gene mapping to human chromosome 21q22.2.
AB  - We have identified a human homologue of the Drosophila mnb gene (MNBH) on
      chromosome 21, while another study mapped an EST clone (R38268) with similarity
      to minibrain to human chromosome 1. This report describes the mapping of MNBH to
      a single locus on human chromosome 21q22.2 by FISH and Southern blotting.
      Comparison of the similarities between the two sequences and mnb demonstrates
      that MNBH on chromosome 21 is the true human homologue of Drosophila mnb.

PMID- 9284913
TI  - Assignment of the L32 ribosomal protein gene (RPL32) to human chromosome 3q13.3-
      >q21 by in situ hybridization.

PMID- 9284912
TI  - Isolation and mapping of a human zinc finger gene (ZNF188) homologous to ZNF187,
      a serum-response-element binding protein.
AB  - From a human pancreas cDNA library we isolated and characterized a novel zinc
      finger gene encoding a protein homologous to ZNF187, a serum response element
      binding protein. The full-length cDNA contained an open reading frame of 1,686
      nucleotides encoding a predicted 562-amino-acid peptide that included an ATP-GTP
      binding site and seven C2H2 zinc finger domains. The consensus sequence of the
      C2H2 domains (CX2CX3FX5LX2HX3H) is common in the SRE-binding region present in
      Drosophila Kruppel proteins. An alternatively spliced form of the transcript
      found in the cDNA library lacked both the ATP-GTP binding site and any C2H2 zinc
      finger domains. We localized this gene (ZNF188) to chromosome band 7q22.1-->q22.3
      by fluorescence in situ hybridization.

PMID- 9284914
TI  - Microdissection-mediated selection of chromosome region-specific cDNAs.
AB  - K562 is a cell line with two acrocentric marker chromosomes containing abnormally
      banded regions (ABRs), derived from a Ph-positive chronic myelogenous leukemia
      (CML) patient. Using reverse and forward chromosome painting FISH analysis, we
      found that 9q34, 13q31, and 22q11 regions co-amplified in the ABRs-bearing
      acrocentric marker chromosomes of K562. Utilizing the ABRs of the cell line as
      target DNA for cDNA selection, we established a simple procedure for chromosome
      region-specific cDNA isolation. After first strand cDNA synthesis from fetal
      brain mRNAs, short fragment cDNAs (sf-cDNAs) were synthesized with a two-step
      amplification system by use of our modified Degenerate Oligonucleotide Primed
      Shuttle Polymerase Chain Reaction (DOP-Shuttle-PCR) method. The sf-cDNAs were
      hybridized onto RNase A treated metaphases from K562, and the ABRs were
      microdissected and reamplified with DOP-Shuttle-PCR primer-II. The reamplified sf
      cDNAs were cloned into a pBluescript vector. Twenty randomly chosen clones were
      sequenced and classified into 8 groups. Three out of the 8 grouped clones had
      been mapped to the long arm of chromosome 22 (22q11), whereas the other 5 were
      novel cDNAs. Quantitative Southern blot analysis indicated that 7 out of the 8
      grouped clones (87.5%) were derived from the co-amplified regions.

PMID- 9284915
TI  - Regional assignment of 64 human gene transcripts on chromosome 8.
AB  - A panel of somatic cell hybrids specific for human chromosome 8 was used to
      localize 64 expressed sequence-tagged site (ESTS) markers to six individual
      regions by PCR amplification. Nine ESTS correspond to 8 known human genes and 6
      others show similarities with vertebrate genes, whereas the remaining 49 ESTS
      markers correspond to novel genes with no database similarities. These gene
      transcript markers will contribute to the developing physical and expression maps
      of chromosome 8, and to the search for candidate genes for various human
      diseases.

PMID- 9284917
TI  - Assignment of SATB1 to human chromosome band 3p23 by in situ hybridization.

PMID- 9284916
TI  - Chromosome location of sixteen genes in the common shrew, Sorex araneus L.
      (Mammalia, Insectivora).
AB  - This report extends the genetic map of the common shrew (Sorex araneus) by use of
      a clone panel of shrew-Chinese hamster and shrew-mouse hybrid cells (Pack et al.,
      1995; Matyakhina et al., 1996). This set of hybrid clones made it possible to
      assign the shrew genes for isocitrate dehydrogenase 2 (IDH2), inorganic
      pyrophosphatase (PP), glutamicpyruvate transaminase (GPT), adenosine kinase
      (ADK), glucuronidase 2 (GUSB) and acid phosphatase 2 (ACP2) to chromosome ik; the
      genes for adenylate kinases 1 and 3 (AK1 and AK3) to chromosome af; the genes for
      glutamate-oxaloacetate transaminase 2 (GOT2), peptidase D (PEPD) and growth
      hormone (GH) to chromosome hn; the gene for phosphoglucomutase 2 (PGM2) to
      chromosome go, the gene for enolase 1 (ENO1) to chromosome ji, the gene for
      ornithine carbamoyl-transferase (OTC) to chromosome de, the gene for aminoacylase
      1 (ACY1) to arm m (chromosome mp), the gene for glutamate-oxaloacetate
      transaminase 1 (GOT1) to arm q (chromosome qr). Thus, the genetic map of the
      common shrew now contains 33 genes and it is possible to compare the syntenic
      associations with other species.

PMID- 9284918
TI  - cDNA cloning, expression and chromosome mapping of the human STAT4 gene: both
      STAT4 and STAT1 genes are mapped to 2q32.2-->q32.3.
AB  - Studies of transcriptional activation by interferons and a variety of cytokines
      have led to the identification of a family of proteins that serve as signal
      transducers and activators of transcription (STAT). STAT4 is phosphorylated
      following interleukin (IL)-12 stimulation and is essential for IL-12 signal
      transduction. The human STAT4 cDNA was cloned, and both STAT4 and STAT1 genes
      were mapped to human chromosome bands 2q32.2-->q32.3 by fluorescence in situ
      hybridization. These results suggest that STAT4 and STAT1 may have arisen via a
      tandem gene duplication. However, human STAT1 is expressed ubiquitously, whereas
      human STAT4 is expressed in several tissues including spleen, heart, brain,
      peripheral blood cells, and testis.

PMID- 9284919
TI  - Conservation of human vs. feline genome organization revealed by reciprocal
      chromosome painting.
AB  - We employed fluorescence in situ hybridization (FISH) with probes established by
      flow sorting metaphase chromosomes of the domestic cat (Felis cattus, 2n = 38) to
      "paint" homologous segments on human chromosomes and, reciprocally, using human
      chromosome paints on feline metaphase preparations. The results revealed, by
      direct microscopic observation, widespread conservation of genome organization
      between the two mammalian orders and confirmed 90% of the homologous genes mapped
      to both species. Fourteen of 23 human chomosomes were hybridized with single cat
      probes, and 9 of 19 cat chromosomes were entirely labeled by a single human
      probe. All other chromosomes were labeled with only two or, at most, three probes
      of the respective species. Y-chromosome probes gave no signals. Approximately 30
      syntenic segments were identified, and the number of translocations could be
      estimated to be on the order of one new translocation per 10 million years in the
      phylogenetic lines leading to human and cat. Using the principle of maximum
      parsimony, the primitive vs. derived human chromosome segments were identified by
      comparison to the feline, cattle, and pig genomes, a first step in reconstructing
      the evolutionary heritage of the mammalian radiations. The results suggest that
      reciprocal chromosome painting will help reconstruct the history of genomic
      changes by determining the polarity of chromosomal rearrangements and
      establishing the ancestral karyotype for each principle branching point in
      mammalian evolution.

PMID- 9284920
TI  - X chromosome evolution in the suni and eland antelope: detection of homologous
      regions by fluorescence in situ hybridization and G-banding.
AB  - Comparative cytogenetics and fluorescence in situ hybridization (FISH) were used
      to track structural rearrangements in the X chromosomes of two African antelope
      species, the eland (Taurotragus oryx; tribe Tragelaphini) and the suni (Neotragus
      moschatus; tribe Neotragini). Using two microdissected cattle chromosome painting
      probes (one specific for Xp-containing sequences corresponding to Xp24-->p12 of
      the cattle X, and one specific for Xq-containing sequences corresponding to Xq12-
      >qter), we show that intrachromosomal rearrangements distinguish the X
      chromosomes of these species. Furthermore, there is clear evidence that,
      superimposed on this background of intrachromosomal evolutionary change, the
      sequences contained in the cattle Xp painting probe appear to have moved as a
      complete unit during the repatterning of the bovid X. Although we are unable to
      infer the order of the rearranged chromosomal segments, given the large regions
      of homology detected by the chromosome paints, we nonetheless believe that this
      approach (combining conventional and molecular cytogenetic studies on the X
      chromosome) will prove useful for inferring phylogenetic relationships in the
      family Bovidae, particularly as more probes become available.

PMID- 9284921
TI  - Segmental homology among cattle (Bos taurus), Indian muntjac (Muntiacus muntjak
      vaginalis), and Chinese muntjac (M. reevesi) karyotypes.
AB  - In an attempt to examine homologies between Indian and Chinese muntjac karyotypes
      at a subchromosomal level, five bovine cosmids were comparatively mapped by
      heterologous fluorescence in situ hybridization (FISH). In the Indian muntjac (2n
      = 6) all cosmids mapped to chromosome 1, whereas in the Chinese muntjac (2n = 46)
      two cosmids mapped to chromosome 3 and one cosmid each mapped to chromosomes 1,
      7, and 17. These markers have maintained their intrachromosomal position relative
      to a centromere/telomere axis in cattle and in Chinese and Indian muntjac
      chromosomal arms. Our results corroborate the tandem-fusion hypothesis for
      muntjac karyotypic evolution and establish orientational homology between the
      involved Chinese muntjac chromosomes and the discrete segments on Indian muntjac
      chromosome 1. Furthermore, our data disclose regional homologies between cattle
      and muntjac genomes and demonstrate the validity of intergeneric cosmid-FISH for
      investigations on karyotype evolution.

PMID- 9284922
TI  - Assignment of Chinese hamster p53 gene (TP53) to chromosome band 2p31, a region
      not involved in the karyotypic changes of a tumorigenic cell line.
AB  - The Chinese hamster tumor-derived cell line 835T2 exhibits specific karyotypic
      changes, including the loss and/or translocation of genetic material. To
      investigate whether the p53 tumor suppressor gene was involved in the exchanges,
      cDNA from primary Chinese hamster cells was isolated by using sense and antisense
      primers of the human p53 gene. The cDNA was sequenced, and the sequence was
      compared with the Syrian and human p53 cDNA reported sequences. The sequence
      homology was very elevated, demonstrating that the cloned fragment contained part
      of the Chinese hamster p53 gene. The corresponding genomic fragment was also
      cloned and used as a biotin-labeled probe for in situ hybridization on Chinese
      hamster chromosome spreads. Hybridization was visualized by avidin-FITC, and the
      assignment was done comparing the banding obtained with BamHI restriction enzyme
      and the location of the fluorescent signals pattern of the same metaphase. The
      signals revealed that the p53 gene (TP53) is localized on Chinese hamster
      chromosome band 2p31, which is not involved in the karyotypic changes specific to
      the 835T2 cell line.

PMID- 9284923
TI  - A panel of radiation hybrids and YAC clones specific for human chromosome 5.
AB  - We report the characterization, by reverse fluorescence in situ hybridization
      (FISH), of 59 hybrids retaining fragments of human chromosome 5. Most of these
      hybrids are radiation hybrids generated by gamma irradiating, at low dosage, a
      monochromosomal hybrid retaining chromosome 5 as its only human contribution. The
      partial chromosome paints generated from these hybrids will make powerful tools
      for cytogenetic investigations, especially on the cytogenetic evolution of
      primates, and examples are reported. The molecular characterization of these
      hybrids was refined using 74 sequence-tagged sites (STSs), which allowed the
      physical dissection of chromosome 5 into 71 distinct regions with an average
      length of 2.7 Mb. The panel, therefore, is also suitable for high-precision
      subregional mapping of new genes or sequences located on chromosome 5. As an
      additional resource for cytogenetic studies involving chromosome 5, we report the
      characterization, by FISH, of 73 YACs from CEPH. The vast majority of these YACs
      are recognized by at least one of the STSs used for hybrid characterization, thus
      enabling the integrated use of YACs and partial chromosome paints derived from
      the hybrids.

PMID- 9284924
TI  - Comparative analysis of Y chromosome structure in Bos taurus and B. indicus by
      FISH using region-specific, microdissected, and locus-specific DNA probes.
AB  - Results of fluorescence in situ hybridization (FISH) of Bos taurus and B. indicus
      Y chromosomes using the bovine locus-specific Y probes BC1.2 and lambda ES6.0 and
      region-specific probes of B. indicus and B. taurus Y chromosomes, which were
      generated by microdissection and DOP-PCR, indicate that the Y chromosomes of B.
      indicus (BIN Y) and B. taurus (BTA Y) differ by a pericentric inversion. Parts of
      the short and long arms of the Y chromosome in B. taurus and the distal half of
      the Y chromosome in B. indicus were microdissected, amplified by DOP-PCR,
      biotinylated, and rehybridized in situ to the corresponding metaphase chromosomes
      to test the chromosome fragment specificity of the DNA probes. The region
      specific painting probes were used for hybridization to metaphase chromosomes of
      the other species. The DNA painting probes BTA Yp12 and BTA Yq12.1-ter derived
      from BTA Y hybridized to the distal and proximal halves of BIN Y, respectively.
      Complex hybridization signals on BTA Yq12.1-->qter were generated with the DNA
      probe BIN Yqcen-centr (centromere-central) after FISH. The results demonstrate
      that BTA Yp is homologous to the distal half of BIN Y and that BTA Yq corresponds
      to the proximal part of BIN Yq. Hybridization of the Y chromosome-specific DNA
      probes lambda ES6.0 to BTA Yp12-->p11 and near to the telomere of BIN Y and BC1.2
      to BTA Yq12-->q13 and to the telomere of BIN Y indicate an opposite orientation
      of the homologous chromosome fragments BTA Yp and of the distal half of BIN Yq.

PMID- 9284925
TI  - Shared synteny between human chromosome 10 and chromosome 1 of the marsupial
      tammar wallaby, Macropus eugenii.
AB  - Marsupial homologs of the human chromosome 10 loci IL2RA, HK1, and PLAU have been
      cloned and mapped by fluorescence in situ hybridization to chromosome 1q of the
      tammar wallaby, Macropus eugenii. Relative distance measurements of the
      hybridization signals on M. eugenii chromosome 1 show that marsupial homologs of
      human (HSA) 10p IL2RA and 10q HK1/PLAU flank the marsupial homologs of the human
      5q gene IL5 and the human 15q imprinted genes SNRPN and ZNF127. The shared
      synteny, therefore, does not necessarily mean that HSA 10 represents an ancestral
      grouping; rather, it suggests that HSA 10p and HSA 10q represent two different
      ancestral mammalian units which fused directly in primates and were incorporated
      independently into two different regions of the same chromosome in marsupials.

PMID- 9284926
TI  - Development of diagnostic tools for the analysis of 5p deletions using interphase
      FISH.
AB  - Cri-du-chat syndrome is associated with a deletion of the short arm of chromosome
      5. Through the phenotypic and molecular analyses of individuals with a subset of
      the features associated with the syndrome, the genes involved in the syndrome
      have been mapped to two distinct critical regions. Deletion of a critical region
      in 5p15.2 results in the distinct facial features associated with the syndrome as
      well as the severe mental and developmental delay, while a deletion of 5p15.3 is
      associated only with the characteristic cat-like cry, the key diagnostic feature
      of the syndrome. Therefore, subtle differences in the extent of the 5p deletion
      can have a profound affect on the prognosis of the patient. In order to more
      easily differentiate between deletions that lead to the cri-du-chat syndrome
      phenotype and deletions that lead only to the isolated cat-like cry, we have
      constructed YAC contigs that span both critical regions. The YAC clones have been
      used to isolate cosmids mapping to each critical region and cosmids that lie just
      within the two critical region boundaries have been identified. We report here on
      the use of these cosmids as probes for fluorescent in situ hybridization
      experiments on interphase nuclei as a means of more accurately differentiating
      between small 5p deletions that coincide with a complete cri-du-chat syndrome
      phenotype and the severe mental and developmental delay that is associated with
      it and deletions that only delete the distal critical region that coincide with
      the isolated cat-like cry and a much improved prognosis.

PMID- 9284927
TI  - Assignment of death associated protein 3 (DAP3) to human chromosome 1q21 by in
      situ hybridization.

PMID- 9284928
TI  - Comparative genomic hybridization analysis of Y79 and FISH mapping indicate the
      amplified human mitochondrial ATP synthase alpha-subunit gene (ATP5A) maps to
      chromosome 18q12-->q21.
AB  - The four mitochondrial ATP synthase alpha-subunit (ATP5A) genes map to
      chromosomes 2, 9, 16, and 18. In this study we have refined the localization of
      two of these genes by fluorescence in situ hybridization (FISH) to metaphase
      spreads, and further characterised the involvement of ATP5A in the amplification
      process in the retinoblastoma cell line Y79. Comparative genomic hybridization
      (CGH) analysis of Y79 indicated that gene amplification was present on both the
      short arm of chromosome 2 and the long arm of chromosome 18. FISH indicated that
      the functional ATP5A gene mapped to 18q12-->q21, the same band location
      identified by CGH analysis of Y79. An ATP5A pseudogene (ATP5AP1) maps to 9p12.
      Gains in chromosomal material at 18q12-->q21 likely involve hybridization to
      amplified copies of the ATP5A gene while gains at 2p24 represent hybridization to
      the MYCN and DDX1 genes, also amplified in Y79.

PMID- 9284929
TI  - Assignment of IL12RB1 and IL12RB2, interleukin-12 receptor beta 1 and beta 2
      chains, to human chromosome 19 band p13.1 and chromosome 1 band p31.2,
      respectively, by in situ hybridization.

PMID- 9284930
TI  - Assignment of the human nebulin gene (NEB) to chromosome band 2q24.2 and the
      alpha 1 (III) collagen gene (COL3A1) to chromosome band 2q32.2 by in situ
      hybridization; the FRA2G common fragile site lies between the two genes in the
      2q31 band.

PMID- 9284931
TI  - Cloning and chromosome assignment to 1q32 of a human cDNA (RAB7L1) encoding a
      small GTP-binding protein, a member of the RAS superfamily.
AB  - A full-length cDNA homologous to RAB7, a member of the RAB-related GTP-binding
      protein subfamily, was isolated from a human placenta cDNA library. This cDNA,
      designated RAB7L1, has an open reading frame of 609 nucleotides encoding 203
      amino acids. Northern analysis showed that the mRNA is ubiquitously expressed in
      human tissues, although signal intensities were different among the various
      organs examined. This gene was located on chromosome band 1q32 by fluorescence in
      situ hybridization.

PMID- 9284932
TI  - Assignment of the gene for a ubiquitin fusion degradation protein (Ufd1l) to
      mouse chromosome 16B1-B4, syntenic with the Tuple1 gene.

PMID- 9284933
TI  - Assignment of hexokinase types 1,2,3 (Hk1,2,3) and glucokinase (Gck) to rat
      chromosome band 20q11, 4q34, 17q12 and 14q21 respectively, by in situ
      hybridization.

PMID- 9284934
TI  - MCM4 and PRKDC, human genes encoding proteins MCM4 and DNA-PKcs, are close
      neighbours located on chromosome 8q12-->q13.
AB  - A human genomic DNA fragment containing the 5' region of MCM4, a gene encoding
      replication protein MCM4/Cdc21 was isolated. At a distance of about 800 base
      pairs upstream of MCM4, the fragment was shown to also contain the 5' end of
      PRKDC, a gene encoding the catalytic subunit of the DNA-dependent protein kinase
      (DNA-PKcs). The genomic DNA fragment was used for hybridization to human
      metaphase chromosome spreads. The cytogenetic map location of the two closely
      adjacent genes was determined to be 8q12-->q13.

PMID- 9284935
TI  - Assignment of the human PTK6 gene encoding a non-receptor protein tyrosine kinase
      to 20q13.3 by fluorescence in situ hybridization.

PMID- 9284936
TI  - Localization of the 18S, 5.8S and 28S rRNA genes and the 5S rRNA genes in the
      babirusa and the white-lipped peccary.
AB  - The locations of the genes encoding 18S, 5.8S and 28S rRNA and 5S rRNA were
      studied in two relatives of the domestic pig, the babirusa (Babyrousa babyrussa)
      and the white-lipped peccary (Tayassu pecari). In the babirusa, the 18S, 5.8S and
      28S rDNA is located on chromosomes 6, 8 and 10. The genes on chromosomes 8 and 10
      are actively transcribed, in contrast to those on chromosomes 6. In the white
      lipped peccary, this rDNA was found to be located on chromosomes 4 and 8. The
      genes on both of these pairs of chromosomes are actively transcribed. The 5S rDNA
      was physically mapped to chromosome 16 in the babirusa, and to chromosome 11 in
      the white-lipped peccary. These data are compared to similar data obtained for
      the domestic pig, and confirm previously recognized chromosome homologies.

PMID- 9284938
TI  - Assignment of C1QBP encoding the C1q globular domain binding protein (gC1q-R) to
      human chromosome 17 band p13.3 by in situ hybridization.

PMID- 9284937
TI  - Isolation, characterization and chromosomal localization of human WNT10B.
AB  - The Wnt family constitutes a set of structurally related glycoproteins that have
      been implicated in oncogenesis and developmental processes. The vertebrate Wnt10
      family includes mouse, Xenopus and salamander proteins. We undertook a
      bioinformatics based approach to characterize a novel human Wnt gene. The gene
      (WNT10B) encodes a 389-amino acid protein with 96.6% sequence identity to mouse
      Wnt10b. The expression pattern of WNT10B reveals that it is synthesized in many
      adult tissues with the highest levels found in heart and skeletal muscle. WNT10B
      expression was also detected in several human cancer cell lines with elevated
      mRNA levels observed in HeLa (cervical cancer) cells. WNT10B was localized to
      12q13.1 by PCR typing of a human/rodent monochromosomal panel and fluorescent in
      situ hybridization.

PMID- 9284939
TI  - Assignment of the canalicular multispecific organic anion transporter gene
      (CMOAT) to human chromosome 10q24 and mouse chromosome 19D2 by fluorescent in
      situ hybridization.
AB  - Rabbit epithelial basolateral chloride conductance regulator (EBCR) and rat
      canalicular multispecific organic anion transporter (Cmoat) are found to be
      homologues based on protein sequence comparison and Northern blot analysis.
      EBCRis, therefore, renamed as rabbit Cmoat. The gene encoding CMOAT, a
      transporter possibly involved in Dubin-Johnson syndrome in humans, is mapped on
      human chromosome 10q24 and mouse chromosome 19D2.

PMID- 9284940
TI  - Assignment of WNT7B to human chromosome band 22q13 by in situ hybridization.

PMID- 9284941
TI  - Mapping AAC1, AAC2 and AACP, the genes for arylamine N-acetyltransferases,
      carcinogen metabolising enzymes on human chromosome 8p22, a region frequently
      deleted in tumours.
AB  - Arylamine N-acetyltransferases (NATs) are encoded at two loci on 8p22, a region
      subject to deletions in bladder tumours. The two functional genes (AAC1 and AAC2
      alias NAT1 and NAT2) without introns in the coding region, encode enzymes which
      metabolise carcinogens, including bladder carcinogens. They are both multi
      allelic and certain alleles have been implicated as susceptibility factors in
      bladder cancer. There is a third N-acetyltransferase gene, a pseudogene, AACP
      alias NATP, which we show is also located on chromosome 8 at the p22 region. We
      have mapped a series of YAC clones (ICI and CEPH) containing the NAT genes and
      the markers D8S21, an RFLP marker, and D8S261, a microsatellite marker. We show
      that D8S21 is a portion of the coding region of AAC2. The order of genes in this
      region, covering some 2 Mb, is TEL-D8S261-AAC1-AACP-AAC2 (D8S21)-CEN. The
      restriction map also illustrates that there are likely to be other expressed
      genes in the region through the identification of CpG islands.

PMID- 9284942
TI  - Comparative genomic hybridization analysis of Wilms tumors.
AB  - In this study we have applied the technique of comparative genomic hybridization
      (CGH) to a large series of sporadic Wilms tumors, including six samples of the
      associated nephroblastomatosis. The data obtained were compared with the findings
      of molecular studies carried out on the same material. The aims of the study were
      (1) to characterize the range of genetic variation in sporadic Wilms tumor and
      nephroblastomatosis, (2) to determine whether changes could be found that have
      not been detected by commonly used techniques, and (3) to compare the sensitivity
      of CGH with that of conventional molecular analysis. The chromosomes that showed
      gains and losses by CGH were similar to those previously found in molecular and
      cytogenetic studies, however loss of 4q was a new event identified in 2 out of 46
      tumors. We did not detect amplified genetic material. Comparison of the data from
      the nephroblastomatosis and tumor samples from the same patient showed that loss
      of 7p may be associated with malignant transformation, and that losses in 1p,
      11p, 4q and gains in 1q and 12q can be early events; whilst loss in 9p and gain
      of 8, 10q and 18 are possible secondary changes in tumor development. The
      combined CGH and molecular techniques used demonstrated involvement of two
      specific 1p regions in the etiology of Wilms tumor.

PMID- 9284943
TI  - Assignment of renal-specific Na(+)-phosphate cotransporter gene Slc17a2 to mouse
      chromosome band 13B by in situ hybridization.

PMID- 9284945
TI  - Undermethylation of Alu sequences in ICF syndrome: molecular and in situ
      analysis.
AB  - The methylation status of young Alu sequences was investigated in four ICF
      patients. In fibroblast and leukocyte DNAs, Alu repeats were either
      undermethylated (HhaI and HpaII digestion) or demethylated (BstUI digestion), in
      contrast with the methylated status of Alus in control subjects. The methylation
      profile exhibited in ICF patients reproduces the normal profile of placental or
      sperm DNA. High-sensitivity immunocytochemical detection of HhaI and HpaII
      restriction sites on metaphase chromosomes provided further evidence of this
      undermethylation. The DNA methylation defect in ICF patients, first detected in
      satellite DNAs (constitutive heterochromatin) and CpG islands of genes on the
      inactive X chromosome (facultative heterochromatin), thus includes Alu sequences
      that are widely distributed throughout the human genome.

PMID- 9284944
TI  - Assignment of the beta-nerve growth factor (NGFB) to bovine chromosome 3 band q23
      by in situ hybridization.

PMID- 9284946
TI  - The human chromosome 3 gene cluster ACY1-CACNA1D-ZNF64-ATP2B2 is evolutionarily
      conserved in Ateles paniscus chamek (Platyrrhini, Primates).
AB  - Comparative mapping of Ateles paniscus chamek and man indicated that four human
      3p markers are syntenic in this karyotypically rearranged neotropical primate.
      The evolutionary conservation of this gene cluster includes three adjacent human
      shortest regions of overlap (SROs): 3p21.1 (ACY1), 3p21.3-->p21.2 (CACNA1D), and
      3p21.3 (ZNF64). A fourth syntenic marker (ATP2B2), at a more distal human SRO
      (3p26-->p25), indicated that human 3pter-->p14 is evolutionarily conserved in
      Ateles chromosome 3 (APC 3). Conversely, allocations of two human 3q markers
      (AGTR1 and IL12A) clearly excluded APC 3. Finally, allocation of the major
      histocompatibility complex class I genes further confirmed human 6p-6q
      dissociations in Ateles.

PMID- 9284947
TI  - Novel signal transduction and peptide specificity of glucagon-like peptide
      receptor in 3T3-L1 adipocytes.
AB  - Glucagon-like peptide-1 (7-36) amide (GLP-1), in addition to its well known
      effect of enhancing glucose-mediated insulin release, has been shown to have
      insulinomimetic effects and to enhance insulin-mediated glucose uptake and lipid
      synthesis in 3T3-L1 adipocytes. To elucidate the mechanisms of GLP-1 action in
      these cells, we studied the signal transduction and peptide specificity of the
      GLP-1 response. In 3T3-L1 adipocytes, GLP-1 caused a decrease in intracellular
      cAMP levels which is the opposite to the response observed in pancreatic beta
      cells in response to the same peptide. In 3T3-L1 adipocytes, free intracellular
      calcium was not modified by GLP-1. Peptide specificity was examined to help
      determine if a different GLP receptor isoform was expressed in 3T3-L1 adipocytes
      vs. beta cells. Peptides with partial homology to GLP-1 such as GLP-2, GLP-1 (1
      36), and glucagon all lowered cAMP levels in 3T3-L1 adipocytes. In addition, an
      antagonist of pancreatic GLP-1 receptor, exendin-4 (9-39), acted as an agonist to
      decrease cAMP levels in 3T3-L1 adipocytes as did exendin-4 (1-39), a known
      agonist for the pancreatic GLP-1 receptor. Binding studies using 125I-GLP-1 also
      suggest that pancreatic GLP-1 receptor isoform is not responsible for the effect
      of GLP-1 and related peptides in 3T3-L1 adipocytes. Based on these results, we
      propose that the major form of the GLP receptor in 3T3-L1 adipocytes is
      functionally different from the pancreatic GLP-1 receptor.

PMID- 9284949
TI  - Nitric oxide induces transient Ca2+ changes in endothelial cells independent of
      cGMP.
AB  - Ca2+ changes induced by nitric oxide (NO.) were investigated in cultured human
      endothelial cells. Sodium nitroprusside (SNP) (1-100 mumol/L) and S-Nitroso-N
      acetylpenicillamine (SNAP) (100 mumol/L) were used as NO. donors. The
      cytoplasmatic Ca2+ concentration was calculated using ratiometric FURA2
      fluorescence measurements. Both NO. donors caused transient oscillatory Ca2+
      changes, which were not detectable in the presence of oxyhemoglobin (50 mumol/L).
      Digital ratio imaging revealed initiation sites within cells where Ca2+ increases
      started spreading, which indicates that nonuniformly distributed targets might be
      involved in these reactions. Calcium was released from intracellular stores as
      indicated by experiments performed in Ca(2+)-free buffer. L-type Ca(2+)-channel
      blocker diltiazem (100 mumol/L) was not able to block these responses. NO.
      induced Ca2+ release from intracellular stores caused capacitative Ca2+ entry.
      Both thapsigargin (1 mumol/L) and cyclopiazonic acid (10 mumol/L) inhibited the
      SNP response completely, whereas neither ryanodine (up to 100 mumol/L) nor
      dantrolene (100 mumol/L) was able to inhibit Ca2+ changes induced by SNP,
      indicating that primarily inositol 1,4,5-triphosphate (IP3)-dependent stores are
      released upon stimulation with NO.. A small inhibitory effect of ATP- and SNP
      induced peak [Ca2+]i increase was measured in the presence of both caffeine (20
      mmol/L) and procaine (1 mmol/L). Evidence is presented that cGMP is not involved
      in NO.-induced Ca2+ signals, as neither inhibitors of guanylate cyclase
      (methylene blue and LY 83583) nor cell permeant analogues of cGMP altered or
      simulated [Ca2+] changes. An inhibitor of cGMP-dependent protein kinase was also
      ineffective. We therefore propose that endothelial cells have specific targets
      proximal or at IP3 receptors to induce Ca2+ changes in endothelial cells
      stimulated with NO..

PMID- 9284948
TI  - Up-regulation of Ca2+ influx mediated by store-operated channels in HL60 cells
      induced to differentiate by 1 alpha,25-dihydroxyvitamin D3.
AB  - The physiologically active form of vitamin D, 1 alpha,25-dihydroxyvitamin D3
      (1,25D3), induces promyelocytic HL60 cells to differentiate towards monocyte-like
      cells. During this differentiation increased cytosolic calcium (Cai2+) and
      expression of surface receptors for chemotactic factors "prime" the cell for the
      activation of monocyte functions and the triggering of the respiratory burst
      pathway. We examined whether the Ca2+ influx mediated by store-operated channels
      (SOC) contributed to the increased Cai2+ following exposure of HL60 cells to 10(
      7) M 1,25D3. Cells treated with 1,25D3 for 72 hr demonstrated a rapid transient
      rise in Cai2+ followed by a second, phasic, increase in Cai2+ in response to the
      purinergic agonist ATP. This second Cai2+ transient was blocked by Ni2+, SKF
      96365, or withdrawal of extracellular Ca2+. In cells suspended in Ca(2+)-free
      medium, peak changes (delta) in [Ca2+]i elicited by ATP-induced Ca2+ mobilization
      occurred with similar EC50 values in differentiated and vehicle (EtOH)-treated
      cells; however, peak [Ca2+]i was reduced by 55% in 1,25D3-treated cells.
      Decreased Ca2+ mobilization was associated with a 25-35% reduction in
      intracellular Ca2+ stores (determined with ionomycin). 1,25D3-treated cells
      exposed to ATP or thapsigargin (Tg) in Ca(2+)-free medium for 3 min with
      subsequent addition of 1 mM Ca2+ exhibited a respective 80% or 120% stimulation
      in peak [Ca2+]i compared to EtOH-treated cells. Enhanced Ca2+ influx mediated by
      SOC was also seen in these cells as an increase in the rate of Mn2+ entry after
      exposure to ATP or Tg. At 96 hr after addition of 1,25D3, when differentiated
      phenotype was established, basal Ca2+i and Ca2+ entry mediated by SOC returned to
      control values, but Ca2+ store size remained reduced. Up-regulation of Ca2+
      influx via the SOC pathway during 1,25D3-induced differentiation may contribute
      to the functional properties of the maturing monocyte, or to the resetting of
      molecular programs responsible for the changing phenotype.

PMID- 9284950
TI  - Retinoic acid induced growth arrest of human breast carcinoma cells requires
      protein kinase C alpha expression and activity.
AB  - Retinoic acid inhibits proliferation of hormone-dependent, but not hormone
      independent breast cancer cells. Retinoic acid-induced changes in cellular
      proliferation and differentiation are associated with disturbances in growth
      factor signaling and frequently with changes in protein kinase C expression. PKC
      delta, epsilon, and zeta are expressed in both hormone-dependent (T-47D) and
      hormone-independent (MDA-MB-231) cell lines. Retinoic acid arrested T-47D
      proliferation, induced PKC alpha expression and concomitantly repressed PKC zeta
      expression. The changes in PKC alpha and PKC zeta reflect retinoic acid-induced
      changes in mRNA. In contrast, retinoic acid had no effect on growth, or PKC
      expression in MDA-MB-231 cells. Growth arrest and the induction of PKC alpha, but
      not the reduction in PKC zeta, resulted from selective activation of RAR alpha.
      In total, these results support an important role for PKC alpha in mediating the
      anti-proliferative action of retinoids on human breast carcinoma cells.

PMID- 9284951
TI  - Ultraviolet light attenuates heat-inducible gene expression.
AB  - Ultraviolet light (UV) induces a stress response mediated through transcription
      factors such as NF-kB and AP-1, yet little is known about its effect on other
      transactivators of stress gene expression such as heat shock factor (HSF1).
      Analysis of UV-treated HeLa cells unexpectedly revealed uncoupling of the heat
      shock response. UV weakly induced HSF1 into its DNA bound state and markedly
      attenuated heat-inducible gene expression. HSF1 was further analyzed as a
      potential target for the uncharacteristic uncoupling of the thermal stress
      response by another type of stress. Heat-inducible multimerization and nuclear
      translocation of HSF1 were found to be intact in UV-treated cells; however, the
      monomeric rather than the multimeric form of HSF1 become hyperphosphorylated by
      UV. This effect could be partially abolished by the antioxidant N-acetyl cysteine
      with partial reconstitution of hs gene expression. The reported role of a MAP
      kinase blockade of HSF1 transactivating properties could not be confirmed by an
      inhibitor of the MAP kinase pathway. Fibroblasts defective in SAP kinase activity
      also did not exhibit resistance to UV-inducible phosphorylation of HSF1. Two
      dimensional phosphopeptide mapping of HSF1 revealed a single tryptic peptide to
      be affected by UV, but no new pattern of phosphorylation was evident relative to
      tryptic phosphopeptide profile observed in control cells. These data suggest that
      UV uncoupling of the hs response possibly involves steps in addition to those
      associated with phosphorylation the monomeric form of HSF1.

PMID- 9284952
TI  - Collagen phagocytosis and apoptosis are induced by high level alkaline
      phosphatase expression in rat fibroblasts.
AB  - Study of fibroblast origins and lineages is complicated by the lack of
      unambiguous markers that could be used to identify discrete subpopulations on the
      basis of functional attributes. We have studied the role of the membrane-anchored
      hydrolytic enzyme tissue-nonspecific alkaline phosphatase (TN-AP) and the
      placental alkaline phosphatase (PL-AP) in collagen phagocytosis and in the
      deletion of cells by apoptosis. Rat-2 cells, which do not constitutively express
      AP, were transfected with full-length rat TN-AP or PL-AP cDNAs to determine the
      impact of the TN-AP collagen-binding domain on cell function. Various levels of
      expression were driven by early (strong) or late (weak) SV40 promoters in the
      plasmid construct. Controls were transfected with plasmids that did not contain
      AP cDNA. AP expression in transfected cells was confirmed by Northern blotting,
      histochemical analysis, and SDS-PAGE analysis of membrane-anchored enzyme
      released by phosphatidyl inositol phospholipase C. Low levels of TN-AP expression
      increased cell spreading slightly, nearly doubled the percentage of collagen
      phagocytic cells (up to 80%), and increased the number of internalized collagen
      coated fluorescence beads per cell. In cells transfected with PL-AP (i.e., no
      collagen-binding domain), collagen phagocytosis was not affected. Internalization
      of BSA beads was also not affected by either AP isozyme, indicating that AP was
      selective for integrin-mediated phagocytosis. In single cells, histochemically
      demonstrable TN-AP activity on cell membranes was colocalized with the binding of
      collagen beads, but this colocalization was not detected in cells transfected
      with PL-AP. Phagocytosis was inhibited by antibodies to the alpha 2 integrin and
      to AP but not by levamisole, an inhibitor of AP phosphohydrolytic activity. High
      level TN-AP expression caused a fivefold reduction of cell proliferation and was
      associated with the development of cells with sub-G1 DNA content, nuclear
      condensation, and nuclear budding. In AP-positive cultures, there was a greatly
      increased number of floating cells; nick-labeling of DNA by terminal transferase
      and biotinylated dUTP showed a 15-fold increase of stained cells. These data
      indicate that low-level TN-AP expression enhances collagen phagocytosis,
      presumably through the TN-AP collagen-binding domain. High-level AP expression
      promotes cell deletion by apoptosis. We suggest that the expression of AP by
      fibroblasts indicates a novel role for this enzyme in collagen degradation by
      phagocytosis.

PMID- 9284953
TI  - Specific degradation of subendothelial matrix proteoglycans by brain-metastatic
      melanoma and brain endothelial cell heparanases.
AB  - One of the many features of the malignant phenotype, in vitro and in vivo, is
      elevated heparanase production and activity. Using in vitro model systems, we
      examined the capacity of murine (B16B15b) and human (70W) brain-metastatic
      melanoma cells to degrade the subendothelial matrix produced by endothelial cell
      monolayer cultures. B16B15b and 70W melanoma cells solubilized sulfated matrix
      proteoglycans at levels significantly higher than their parental lines (B16F1,
      MeWo). Sulfated matrix proteoglycans were rich in heparan sulfate (HSPGs), with
      minor amounts of chondroitin and dermatan sulfates. When matrix HSPGs were
      treated with pronase and alkaline borohydride to cleave the core proteins, the
      resulting glycosaminoglycan chains (GAGs) had an estimated M(r) of approximately
      2.7 x 10(4) Da, with a minor subpopulation possessing an M(r) of approximately
      4.5 x 10(4) Da. After their incubation with brain-metastatic melanoma cells, new
      HS fragments with lower M(r) estimated at approximately 9 x 10(3) Da were
      detected. This confirms action in these cells of heparanase, which is capable of
      cleaving GAGs at specific intrachain sites and releasing fragments of a
      relatively high M(r). The pattern of HSPG degradation by brain-metastatic
      melanoma cells differed from that of less metastatic parental cells or cells
      metastatic to organs other than the brain. Moreover, supraadditive levels of
      heparanase activity were found when brain endothelial cells were coin-cubated
      with brain-metastatic melanoma cells in equicellular amounts. Cooperative
      interactions between heparanases from tumor and endothelial sources in the
      invasion process are suggested and their potential mechanisms discussed.

PMID- 9284954
TI  - In human salivary gland cells, overexpression of E2F1 overcomes an interferon
      gamma- and tumor necrosis factor-alpha-induced growth arrest but does not result
      in complete mitosis.
AB  - Increased levels of cytokines in the salivary glands have been associated with
      the loss of secretory cells and reduced salivary function. It has been
      demonstrated that interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha
      (TNF-alpha) treatment of a human submandibular gland (HSG) cell line causes
      growth arrest in the G0/G1 phase of the cell cycle, followed by apoptosis. To
      stimulate DNA synthesis and reverse this growth arrest, we used an adenovirus
      vector to overexpress the transcription factor E2F1 in HSG cells. Initially,
      cells were synchronized by a double thymidine block and then infected with
      recombinant adenovirus (AdE2F1) expressing E2F1. Cells were harvested at
      intervals and analyzed by flow cytometry. Greater than 50% of synchronized cells
      infected with AdE2F1 were in S phase by 18 hours postinfection (hpi) compared to
      12% of uninfected cells. Similarly, AdE2F1 infection of HSG cells arrested by IFN
      gamma and TNF-alpha treatment caused a fivefold increase in S-phase cells by 48
      hpi. However, by 72 hpi, AdE2F1-infected cells showed increases in the subdiploid
      cell population. Forty-one percent of AdE2F1-infected cells labeled positive by
      TUNEL, compared to fewer than 6% for controls. Additionally, AdE2F1-infected
      cells (84 hpi) had low forward-angle and high side scatter light characteristics,
      similar to apoptotic lymphocytes. These results suggest that E2F1 accumulation in
      growth-arrested salivary gland cells can stimulate DNA synthesis and overcome a
      G0/G1 block in the cell cycle. However, E2F1 overexpression did not lead to
      complete mitosis in HSG cells but, rather, diverted cells into an apoptotic
      pathway.

PMID- 9284955
TI  - dl-alpha-tocopherol, a potent inhibitor of phorbol ester induced shape change of
      erythro- and megakaryoblastic leukemia cells.
AB  - Synthetic vitamin E, dl-alpha-tocopherol, added to a human erythroleukemia HEL
      and a megakaryoblastic leukemia, Meg-01, cell culture produced potent dose
      dependent inhibition of phorbol ester-induced adhesion and of the morphologic
      changes accompanying it. The inhibition was reversible by withdrawal of
      supplemental vitamin E from the medium. dl-alpha-Tocopherol also inhibited
      protein kinase C activity both at baseline and after phorbol ester stimulation.
      Arachidonic acid stimulated protein kinase C activity of erythroleukemia cells
      and promoted their adhesion, an effect that was also inhibited by dl-alpha
      tocopherol. Introduction of a protein kinase C-neutralizing antibody or a protein
      kinase C-inhibitor substrate into permeabilized HEL cells inhibited phorbol ester
      induced adhesion and shape change. dl-alpha-Tocopherol also affected the cellular
      distribution of protein kinase C, shifting the major portion of the enzyme to the
      cytosol fraction and reducing phorbol ester-induced membrane association of the
      enzyme. Thus, protein kinase C appears to mediate shape change and adhesion, both
      of which are strongly inhibited by dl-alpha-tocopherol.

PMID- 9284956
TI  - Differential regulation of keratinocyte growth factor and hepatocyte growth
      factor/scatter factor by different cytokines in human corneal and limbal
      fibroblasts.
AB  - Corneal epithelial stem cells and transient amplifying cells are located in the
      limbal and corneal regions, respectively. In a serum-free medium with or without
      different cytokines, limbal fibroblasts consistently produced greater levels of
      keratinocyte growth factor (KGF) transcript and protein than corneal fibroblasts,
      whereas corneal fibroblasts produced greater levels of hepatocyte growth factor/
      scatter factor (HGF/SF) transcript and protein than limbal fibroblasts.
      Expression of HGF/SF transcript and protein was up-regulated mildly by epidermal
      growth factor (EGF), transforming growth factor-alpha (TGF-alpha), or platelet
      derived growth factor B (PDGF-BB) but markedly by interleukin-1 beta (IL-1 beta)
      and was more pronounced in limbal than in corneal fibroblasts. Expression of KGF
      transcript was down-regulated by EGF, TGF-alpha, and PDGF-BB, was markedly up
      regulated by IL-1 beta, and was more pronounced in limbal than in corneal
      fibroblasts. Expression of KGF protein was up-regulated markedly by IL-1 beta and
      moderately by PDGF-BB, especially in limbal fibroblasts. TGF-beta 1 uniquely
      turned off transcript and protein expression of HGF/SF and KGF in corneal
      fibroblasts. Although its transcript levels were similarly down-regulated in
      limbal fibroblasts, KGF protein levels were paradoxically up-regulated by TGF
      beta 1 when added alone or with TGF-alpha or IL-1 beta. These data indicate that
      KGF and HGF/SF, two fibroblast-derived epithelial mitogens, are expressed
      differentially by limbal and corneal fibroblasts and are modulated by cytokines
      activated during epithelial-mesenchymal interactions, suggesting that they may
      play a different role in modulating corneal epithelial stem cells and transient
      amplifying cells.

PMID- 9284958
TI  - Structural and functional analysis of deficient mutants in subunit I of
      cytochrome c oxidase from Saccharomyces cerevisiae.
AB  - Four point mutations in subunit I of cytochrome c oxidase from Saccharomyces
      cerevisiae that had been selected for respiratory incompetence but still
      contained spectrally detectable haem aa3 were analysed. The isolated mutant
      enzymes exhibited minor band shifts in their optical spectra and contained all
      eleven subunits. However, steady state activities were only a few percent
      compared to wild type enzyme. Using a comprehensive experimental approach, we
      first checked the integrity of the enzyme preparations and then identified the
      specific functional defect. The results are discussed using information from the
      recently solved structures of cytochrome c oxidase at 2.8 A. Mutation 167N is
      positioned between haem a and a conserved glutamate residue (E243). It caused a
      distortion of the EPR signal of haem a and shifted its midpoint potential by 54
      mV to the negative. The high-resolution structure suggests that the primary
      reason for the low activity of the mutant enzyme could be that asparagine in
      position 67 might form a stable hydrogen bond to E243, which is part of a
      proposed proton channel. Cytochrome c oxidase isolated from mutant T316K did not
      meet our criteria for homogeneity and was therefore omitted from further
      analysis. Mutants G352V and V380M exhibited an impairment of electron transfer
      from haem a to a3 and ligand binding to the binuclear centre was affected. In
      mutant V380M also the midpoint potential of CuB was shifted by 65 mV to the
      positive. The results indicated for these two mutants changes primarily
      associated with the binuclear centre, possibly associated with an interference in
      the routes and/or sites of protonation which are required for stable formation of
      the catalytic intermediates. This interpretation is discussed in the light of the
      high resolution structure.

PMID- 9284957
TI  - H2O2-induced filamin redistribution in endothelial cells is modulated by the
      cyclic AMP-dependent protein kinase pathway.
AB  - Hypoxia/reoxygenation injury in vitro causes endothelial cell cytoskeletal
      rearrangement that is related to increased monolayer permeability. Nonmuscle
      filamin (ABP-280) promotes orthogonal branching of F-actin and links
      microfilaments to membrane glycoproteins. Human umbilical vein endothelial cell
      monolayers are exposed to H2O2 (100 microM) for 1-60 min, with or without
      modulators of cAMP-dependent second-messenger pathways, and evaluated for changes
      in filamin distribution, cAMP levels, and the formation of gaps at
      interendothelial junctions. Filamin translocates from the membrane-cytoskeletal
      interface to the cytosol within 1 min of exposure to H2O2. This is associated
      with a decrease in endothelial cell cAMP levels from 83 pmoles/mg protein to 15
      pmoles/mg protein. Intercellular gaps form 15 min after H2O2 treatment and
      progressively increase in number and diameter through 60 min. Both filamin
      redistribution and actin redistribution are associated with decreased
      phosphorylation of filamin and are prevented by activation of the cAMP-dependent
      protein kinase pathway. A synthetic peptide corresponding to filamin's C
      terminal, cAMP-dependent, protein kinase phosphorylation site effectively induces
      filamin translocation and intercellular gap formation, which suggests that
      decreased phosphorylation of filamin at this site causes filamin redistribution
      and destabilization of junctions. These data indicate that H2O2-induced filamin
      redistribution and interendothelial cell gap formation result from inhibition of
      the cAMP-dependent protein kinase pathway.

PMID- 9284959
TI  - Telomeres, senescence and cellular radiation response.
AB  - Telomeres shield the ends of chromosomes from degradation and end-to-end fusions.
      They shorten at each cell division and when they reach a critically short length,
      cells arrest in the G1 phase of the cell cycle and undergo senescence. This
      effectively limits the proliferative potential of cells. Senescence functions as
      a tumour suppressor mechanism and appears to contribute to the process of ageing.
      If senescence is circumvented by tumour viruses, proliferation is re-initiated
      until cells enter crisis. Activation of telomerase prevents telomere attrition
      and cells become immortal. Cellular response to ionizing radiation involves
      induction of cell cycle checkpoint arrests and programmed cell death. Because
      radiation produces double strand breaks in DNA, which cause telomere-less
      chromosome ends, radiation response appears to be the result of inappropriate
      induction of cellular senescence mechanisms.

PMID- 9284960
TI  - Biotransformation of the flavonoid tiliroside to 7-methylether tiliroside:
      bioactivity of this metabolite and of its acetylated derivative.
AB  - Incubation of kaempferol-3-O-beta-D-(6"-E-p-coumaroyl)-glucopyranoside
      (tiliroside) (1) with Aspergillus nidulans gives the 7-methyl ether of tiliroside
      (2) which is a new compound. Its structure is determined by spectroscopic
      methods. Cytotoxic studies of 2 and of its acetylated derivative 2a were carried
      out in vitro against fourteen human leukemic cell lines. Results clearly show
      that compound 2 is ineffective against all leukemic cell lines tested. On the
      contrary, compound 2a exhibited cytotoxic activity against four of the cell lines
      (HL60, DAUDI, HUT78 and MOLT3) and additionally, a dose- and time-dependent
      effect on DNA synthesis.

PMID- 9284961
TI  - A cyclic GMP- and G-kinase-dependent effect of azathioprine on migration by human
      neutrophils.
AB  - Relatively high concentrations of azathioprine had an inhibitory effect on
      interleukin 8 (IL-8)- or formyl-methionyl-leucyl-phenylalanine-activated (fMLP)
      chemotaxis by human neutrophils. However, application of low concentrations of
      azathioprine in a concentration gradient gave a chemotactic stimulation to random
      migration. Stimulation of migration was maximal at a concentration of 5 microM
      azathioprine; at higher concentrations stimulation decreased again. The
      activating effect of azathioprine is located in the mercaptopurine moiety of the
      molecule, since mercaptopurine also stimulated neutrophil migration. In contrast
      to some other chemotactic agents such as fMLP and IL-8, an activating
      concentration (5 microM) of azathioprine did not cause an upregulation of CD11b
      expression on neutrophils in suspension. High concentrations of azathioprine (1
      mM) inhibited CD11b expression of fMLP- or IL-8- activated neutrophils; the
      latter could explain the inhibitory effect of azathioprine. Azathioprine caused a
      transient stimulation of cGMP level; inhibitors of guanylate cyclase inhibited
      azathioprine-stimulated migration, suggesting that cGMP was associated with the
      stimulating effect of azathioprine on migration. Antagonists of cGMP-dependent
      protein kinase (G-kinase) strongly inhibited azathioprine-activated migration,
      indicating that the effect of azathioprine proceeds via G-kinase. The antagonists
      had only a marginal effect on inhibition of IL-8-activated chemotaxis by high
      concentrations of azathioprine, thus the G-kinase seems not to be of great
      importance on the inhibitory effect of azathioprine.

PMID- 9284962
TI  - The effects of several ecdysteroids and ecdysteroid agonists on two Drosophila
      imaginal disc cell lines.
AB  - Two Drosophila imaginal disc cell lines, C18+ (sensitive to 20-hydroxyecdysone,
      20HE) and C18R (resistant to 20HE) were exposed to the ecdysteroid agonists
      RH5849 and RH5992 and the ecdysteroids inokosterone, makisterone A and
      muristerone A. All compounds tested were found to have similar effects on the
      cells, comparable to the effects of 20HE, although at different concentrations.
      C18R showed resistance to all compounds, again at varying concentrations. We
      conclude that it is likely that all the compounds tested use the same receptors
      as 20HE, but show maximum effectiveness at different concentrations.

PMID- 9284963
TI  - Properties of the Ca(2+)-activated Cl- current of Xenopus oocytes.
AB  - The properties of the Ca(2+)-activated Cl- current of Xenopus oocytes have been
      investigated by voltage-clamp and injections of D-3-deoxy-3-fluoro-myo-inositol
      1,4,5-trisphosphate (3-F-lnsP3). Following 3-F-InsP3 injection, a transient phase
      of Ca(2+)-activated Cl- current occurred, caused by Ca2+ release from internal
      stores; subsequently, a secondary, long-lasting, current was recorded, signaling
      Ca2+ influx from the exterior (ICRAC). Changes in external Cl- during the
      sustained phase produced the expected shifts in reversal potential (Erev), while
      the conductance varied opposite to the predictions of simple electrodiffusional
      theory. Application of depolarizing pulses soon (10 s) after 3-F-InsP3 injection
      elicited membrane currents exhibiting a single exponential rise. During the
      sustained subsequent phase, the current elicited by depolarizations showed an
      early peak followed by a prominent decline. During the sustained phase, removal
      of calcium from the external solution, or its substitution with Ba2-, abolished
      voltage- and time-dependent components of the depolarization-induced current.
      Slope conductance analysis of the inactivating records revealed, in addition to
      the decline of the Ca(2+)-activated Cl- current, the presence of a second,
      inwardly directed current. This could be identified as a slowly inducible Na+
      current already described in Xenopus oocytes.

PMID- 9284965
TI  - Mental deterioration in childhood epilepsy.
AB  - Mental retardation is detected in 20-30% of children with epilepsy at hospitals
      specializing in treatment of childhood epilepsy. However, the incidence of mental
      deterioration in childhood epilepsy is not high. In this study, mental
      deterioration was found in 52 (1.8%) of the 2,880 children with epilepsy at
      Okayama University Hospital. The patients showing mental deterioration mostly
      suffered from specific epileptic syndromes, such as West syndrome, Lennox-Gastaut
      syndrome, severe myoclonic epilepsy in infancy and epilepsy with continuous spike
      waves during slow wave sleep. These types of epilepsy show generalized
      electroencephalographic (EEG) abnormalities. It is presumed that mental
      deterioration is caused by the total effects of prolonged diffuse EEG
      abnormalities and the age of the patients. Antiepileptic drugs exert a relatively
      minor effect on mental deterioration.

PMID- 9284964
TI  - A role for the hinge/ear domain of the beta chains in the incorporation of AP
      complexes into clathrin-coated pits and coated vesicles.
AB  - The clathrin-associated adaptor protein (AP) complexes drive the polymerization
      of clathrin in coated pits to form coated vesicles. It has previously been shown
      that the carboxyl-terminal hinge/ear domain of the beta 2 chain contains a
      binding site for clathrin and that removal of this domain from APs or from
      isolated beta 2 chains abrogates their ability to form clathrin coats in vitro.
      We show here that the hinge/ear domain is necessary for efficient incorporation
      of AP complexes into coated pits and coated vesicles in cells, a result that is
      consistent with the view that the beta chains indeed provide an important
      interaction between the AP complexes and clathrin.

PMID- 9284966
TI  - Evaluation of exposure to mixed solvents by analysis of urinary metabolites and
      solvents: content ranges.
AB  - To evaluate worker's exposure to mixed solvents, equations for the calculation of
      the biological hazard index, which is defined as biological levels tolerable for
      exposure to mixture, were developed. When biological levels of exposure
      indicators were not affected by coexposure, rules similar to those for airborne
      monitoring could be applied. Namely, when the components had additive effects,
      the biological hazard index was calculated from the concentration of urinary
      metabolites or parent solvents, by an equation which was essentially similar to
      the equation for the calculation of the hazard index. In the present study, the
      confidence limits of the biological hazard index and predictive limits for
      individual specimens were calculated. These equations could be used under the
      condition that the uptake, metabolism and elimination of solvents were
      practically unaffected by coexposure. When urinary metabolites or solvents of
      some components of a mixed solvent alone were determined and those of the
      remaining components were not determined, the concentration of urinary
      metabolites or solvents of remaining components were estimated from the airborne
      concentration of the other components.

PMID- 9284968
TI  - Analysis of the genome of an Epstein-Barr-virus (EBV)-related herpesvirus in a
      cynomolgus monkey cell line (Si-IIA).
AB  - A simian cell line, Si-IIA, harboring Epstein-Barr-virus (EBV)-related
      herpesvirus (Si-IIA-EBV), produces malignant lymphoma in rabbits when
      administered by intravenous inoculation. In this study, we analyzed the Si-IIA
      EBV genome and compared it with human EBV and herpesvirus macaca fascicularis 1
      (HVMF 1), which is associated with B-cell lymphoma developing in SIV-infected
      immunosuppressed monkeys. DNA from Si-IIA-EBV was amplified by the polymerase
      chain reaction using three different primer pairs complementary to human EBV (B95
      8) DNA; two of the primer pairs covered part of the long internal repeat 1 region
      (IR 1) and the third covered part of the BRRF 1 region. Direct sequencing of the
      three PCR products revealed that Si-IIA-EBV DNA had about 82% nucleotide homology
      to the human EBV DNA in all three regions and 92.4% homology to HVMF1 in the IR1
      region. The blotting pattern by Southern blot analysis was different between Si
      IIA-EBV and human EBV.

PMID- 9284969
TI  - Reconstruction of trabecular tissue from human trabecular cells as a
      multicellular spheroid.
AB  - To understand the development of the trabecular meshwork of the eye, floating
      cellular aggregates (multicellular spheroids) were formed from human trabecular
      cells in a non-adherent environment of culture and incubated for up to one month.
      Dissociated trabecular cells formed multicellular spheroids within one day in the
      non-adherent environment, and apoptosis continued to occur in the spheroids which
      had been initially filled with cells. The final structure after one month
      appeared as a meshwork of cells with large extracellular spaces. Epidermal and
      basic fibroblast growth factor (EGF and bFGF) protected trabecular cells in the
      spheroids from apoptosis and, as a result, kept the spheroids filled with cells
      even after one month. In the absence of excess EGF or bFGF, the multicellular
      spheroids grown in vitro from human trabecular cells mimicked the mesh-like
      structure of normal trabecular tissue. In contrast, under an excess of these
      growth factors, spheroids of high cellularity, resembling the abnormal trabecular
      tissues of patients with congenital glaucoma, were formed.

PMID- 9284967
TI  - cDNA cloning, sequence analysis and expression of a mouse 44-kDa nuclear protein
      copurified with DNA repair factors for acid-depurinated DNA.
AB  - We purified a 44-kDa nuclear protein from salt-extract of permeable mouse ascites
      sarcoma cells in an effort to isolate factors involved in the repair of acid
      depurinated DNA. It was copurified with a major AP endonuclease (APEX nuclease)
      by sequential column chromatography then further purified by sodium dodecyl
      sulphate-polyacrylamide gel electrophoresis as a possible DNA repair support
      factor. Its partial amino acid sequences were determined, and a cDNA clone for
      the protein was isolated from a mouse T-cell cDNA library using long degenerate
      oligonucleotide probes deduced from the amino acid sequence. The complete
      nucleotide sequence of the cDNA (1.7 kilobases) was determined. Northern
      hybridization using this cDNA detected two transcripts: 1.8 kb being the major
      one and 2.6 kb being the minor one. The complete amino acid sequence for the
      protein predicted from the nucleotide sequence of the cDNA indicates that the 44
      kDa protein consists of 394 amino acids with a calculated molecular weight of
      43,698. In tests performed thus far, the recombinant 44-kDa protein expressed in
      Escherichia coli has not expressed any repair-support activity. It remains to be
      analyzed whether the protein attains this activity after appropriate
      posttranslational modifications. Most parts of the 44-kDa protein cDNA and the
      deduced amino acid sequence were found to be identical to those of the protein
      p38-2G4, recently reported as a cell cycle-specifically modulated nuclear protein
      of 38kDa. The p38-2G4 may be a truncated form of the present 44-kDa protein.

PMID- 9284971
TI  - Establishment of a new myeloid cell line with i(17q) as the sole chromosomal
      anomaly from the bone marrow of a patient with myelodysplastic syndrome.
AB  - A new myeloid cell line, MTO-94, was established from the bone marrow of a
      patient with myelodysplastic syndrome (MDS). MTO-94 cells matured in culture
      medium without the addition of growth factors, and yielded neutrophils with
      pseudo-Pelger Huet anomaly or hypersegmentation until 6 months. Ten months after
      the start of cell cultivation, MTO-94 consisted of myeloblasts. Surface
      phenotypes were as follows: CD7 90.3%, CD13 99.6%, CD33 75.6%, HLA-DR 96.3% and
      CD34 0.9%. The karyotype was 46, XY i(17q). The proliferation of MTO-94 cells was
      enhanced by rhIL-3, G-CSF, rhGM-CSF and rhSCF but not by rhIL-6 and
      erythropoietin. MTO-94 cells with i(17q) might be useful in the study of
      biological aspects of not only MDS, but also hematological malignancies with
      i(17q) as the sole chromosomal anomaly.

PMID- 9284970
TI  - The role of three-dimensional computed tomography in the management of
      maxillofacial bone fractures.
AB  - The findings of three-dimensional computed tomography (3DCT) and two-dimensional
      computed tomography (2DCT) with helical CT scanning were compared for 21 patients
      with maxillofacial bone fractures. The results of this study suggest that the
      3DCT evaluation can be divided into 3 groups. The first group, in which 3DCT is
      superior to 2DCT, includes severe complicated midface fractures, for example,
      tripod fractures and complicated maxillary bone fractures. The second group, in
      which 3DCT is equal to 2DCT, includes simple fractures, for example, nasal bone
      fractures and isolated zygomatic fractures. In this group, patients and their
      families could easily understand the nature of the fracture and clinical course
      shown by 3DCT as compared with conventional X-ray and 2DCT. The third group, in
      which 3DCT is inferior to 2DCT, includes blowout fractures. Although 3DCT does
      not provide additional information is blowout fractures, helical scanning permits
      clear observation of multiplanar images without artifacts arising from metal
      prostheses by excluding lower slices during image reconstruction. We conclude
      that 3DCT provides useful information, especially in regard to the extent of
      complex fracture lines, as in tripod fractures.

PMID- 9284972
TI  - Cancer cachexia and depressive states: a neuro-endocrine-immunological disease?
AB  - Plasma 5-hydroxytryptamine (serotonin), tryptophan, neopterin and cortisol levels
      were measured in patients with depressive cancer cachexia and in healthy controls
      during the same time period. Patients with advanced cancers had significantly
      raised neopterin, a marker of endogenous gamma-interferon (IFN-gamma) production,
      and cortisol values, but decreased serotonin and tryptophan levels. Much work has
      been done to elucidate the possible role of serotonin in depressive states. IFN
      gamma induces a high level of indoleamine dioxygenase (IDO), a tryptophan
      degrading enzyme, and high cortisol levels induce high tryptophan oxygenase
      activity, which in turn increases metabolism along the tryptophan-nicotinic acid
      pathway. These results suggest that persistent immune activation and intense
      adrenal activity occur in patients with cancer cachexia, resulting in disorders
      involving tryptophan metabolism followed by depression in cancer cachexia.

PMID- 9284973
TI  - Carbon source utilization and isoenzyme analysis as taxonomic aids for toxigenic
      Neosartorya species and their relatives.
AB  - Collection strains representing species belonging to the genus Neosartorya and
      its relatives from section Fumigati of the genus Aspergillus were compared for
      some of their phenotypic features. The examination of both the carbon source
      utilization and isoenzyme patterns provided a useful tool for clustering these
      strains. Many species (e.g. Neosartorya hiratsukae, N. quadricincta, N. spinosa,
      N. aurata, N. aureola) could readily be distinguished from other species based on
      their specific isoenzyme and carbon source utilization spectra. Close
      relationship was observed between the A. fumigatus and N. fischeri strains.
      Aspergillus strain FRR 1266, which also revealed distinct mitochondrial DNA and
      nuclear DNA patterns, and amplified DNA profiles, was the closest relative of the
      recently described N. pseudofischeri species, and could also be distinguished
      from the A. fumigatus strains by its specific carbon source utilization patterns.
      High levels of variability were detected among N. glabra and A. viridinutans
      strains; most of the strains of Australian origin formed distinct clusters.

PMID- 9284974
TI  - Studies on the composition and properties of thermophilic Bacillus populations in
      subterranean thermal waters of Budapest (Hungary).
AB  - A collection of 148 thermophilic Bacillus isolates were obtained from two thermal
      wells (water temperature at about 70 degrees C) in the area of Budapest
      (Hungary). These isolates, furthermore seven authentic thermophilic reference
      strains of Bacillus spp. were submitted to detailed comparative biochemical
      physiological studies. Overall similarities of these strains for 134 unit
      characters were determined by the SSM coefficient and clustering achieved using
      the UPGMA algorithm. According to the results of our computer aided numerical
      taxonomic analyses, numerous metabolic types, varieties and mutants of a single
      Bacillus sp. not identical with the known thermophilic Bacillus species
      constitute the major fraction of the indigenous thermophilic microbial
      communities in the thermal waters of the Pascal and Szechenyi wells. The data
      also revealed, (1) that the most adapted varieties of this Bacillus sp. can form
      the most dense local populations in these subterranean ecological systems.
      Furthermore, it seems to be probable (2) that the cells of the most commonly
      occurring varieties of this Bacillus sp. may be able to migrate in the
      underground thermal water systems between diverse subterranean regions located
      more or less far from one another.

PMID- 9284975
TI  - New drug effects on bacteria, the antiplasmid effect.

PMID- 9284976
TI  - The aftermath of an industrial disaster.
AB  - An explosion in a Danish supertanker under construction in 1994 caused the death
      of six workers and injured 15. Six months later 270 workers took part in this
      study, which analyses the relationships between objective stressors, the workers'
      own feelings and the reactions of their families after the explosion together
      with training, attitude to the workplace, general out-look, and received crisis
      help. Traumatisation, coping style and crisis support was assessed via the Impact
      of Event Scale (IES), the Coping Styles Questionnaire (CSQ) and the Crisis
      Support Scale (CSS). Emotionally, workers and their families were strongly
      affected by the explosion. The IES-score was 17.6 and the invasion score 9.1. The
      degree of traumatisation was higher in the group who had an 'audience position'
      than in the group who was directly hit by the explosion. Training in rescue work
      did not protect against adverse effects. Rescue work had a strong impact on the
      involved. Social support was a significant factor, that seems to buffer negative
      effects. High level of social integration, effective leadership in the situation,
      and professional crisis intervention characterised the disaster situation. All
      the same, 41 per cent of the workers reached the caseness criteria by Horowitz
      (IES > or = 19).

PMID- 9284977
TI  - Inhibition of interleukin-5 with a monoclonal antibody attenuates allergic
      inflammation.
AB  - IL-5 is a prominent and perhaps an essential element in the induction of allergic
      inflammation in human asthma and other allergic diseases. Despite the strong
      biochemical and clinical correlates between lung eosinophilia and asthma, there
      is no clear understanding of how eosinophils exacerbate asthma. Antigen
      administration to sensitized animals produces eosinophilic infiltration that is
      very similar to that in man, and is prevented by administration of a neutralizing
      monoclonal antibody against IL-5. Mice in which the IL-5 gene is absent are
      unable to mount eosinophilic responses to antigen and do not sustain lung damage,
      but otherwise develop normally. The study of the biology of IL-5 has not only
      clarified the links between eosinophilia and airway hyperreactivity, but also
      strongly suggests that anti-IL-5 therapy may be an effective, safe, and novel way
      of treating human asthma and perhaps other eosinophilic diseases. There are many
      different potential approaches to the inhibition of IL-5, but the one most likely
      to provide "proof of principle" in "asthma in the wild" in man is a monoclonal
      antibody against IL-5.

PMID- 9284978
TI  - Analytic aspects of the standardization of allergenic extracts.

PMID- 9284979
TI  - Group 5 determination in Pooideae grass pollen extracts by monoclonal antibody
      based ELISA. Correlation with biologic activity.
AB  - A solid-phase, monoclonal antibody-based ELISA was set up to quantitate group 5
      allergens in pollen extracts of wild and cultivated Pooideae grasses. The method
      was able to evaluate group 5 concentration in mass units with a sensitivity in
      the ng/ml range and a practical working range of 1-100 ng/ml. The group 5 ELISA
      was compared with rocket immunoelectrophoresis for determination of allergen
      levels in several Phleum pratense extracts, and a very good quantitative
      correlation was found (r = 0.98; P < 0.0001). A highly significant correlation (r
      > 0.8) was also obtained in comparing allergenic potency determined by RAST
      inhibition to group 5 content in several wild and cultivated grass species. The
      results proved the usefulness of the method in the standardization of Pooideae
      pollen extracts employed in diagnosis and treatment.

PMID- 9284980
TI  - Effects of ketotifen on symptoms and on bronchial mucosa in patients with atopic
      asthma.
AB  - Ketotifen is marketed throughout the world as an antiallergy drug, but whether it
      affects infiltration of inflammatory cells into airway mucosa is not known. We
      studied the effects of ketotifen on symptoms, pulmonary function, and airway
      inflammation in 25 patients with atopic asthma. Patients took ketotifen (1 mg
      twice daily) or a matching placebo for 8 weeks in a double-blind, parallel-group
      study. Data recorded on diary cards were used for 2 weeks before treatment began,
      and they were used for the last 2 weeks of treatment to study asthma symptoms,
      use of beta 2-agonists, and peak expiratory flow (PEF). Pulmonary function tests,
      bronchial responsiveness to methacholine, and fiberoptic bronchoscopy were
      performed before and after treatment. Biopsy specimens were obtained by
      bronchoscopy. Specimens were stained immunohistochemically with monoclonal
      antibodies against stored eosinophil cationic protein (EG1), the secreted form of
      eosinophil cationic protein (EG2), mast-cell tryptase (AA1), neutrophil elastase
      (NP57), CD3, CD4, CD8, and CD25. The numbers of positively stained cells in the
      lamina propria were counted. Compared with the placebo, the ketotifen-treated
      group exhibited significant improvement of asthma symptoms (P < 0.05) and
      bronchial responsiveness (P < 0.05). This was accompanied by a reduction of EG2+
      eosinophils (P < 0.05), CD3+ T cells (P < 0.001), CD4+ T cells (P < 0.01), and
      CD25+ activated T cells (P < 0.01) in the bronchial mucosa. These results
      suggested that the beneficial effects of ketotifen in bronchial asthma may result
      from consequent inhibition of activated eosinophils and T-cell recruitment into
      the airway. Moreover, ketotifen may relieve allergic inflammation in bronchial
      asthma.

PMID- 9284981
TI  - Exposure chamber for allergen challenge. A placebo-controlled, double-blind trial
      in house-dust-mite asthma.
AB  - Exposure chambers have proven to be valuable tools in the study of reactions to
      aeroallergens, and in monitoring the efficacy of antiallergic therapy. In the
      present study, 15 house-dust-mite-allergic asthmatics and five nonallergic
      volunteers were challenged in a recently developed exposure chamber. The trial
      was performed double-blinded with house-dust-mite allergen or placebo. Patients
      with allergy to house-dust mite (Dermatophagoides pteronyssinus) (Der p) were
      included by positive skin prick test, allergen-specific IgE, and conventional
      bronchial allergen challenge, with nebulizer and mouthpiece. In the exposure
      chamber, a total allergen dose corresponding to 1200 ng Der p 1 was applied. All
      participants kept diaries, recording peak expiratory flow rates, symptoms, and
      medication in periods of at least 2 weeks before and after each challenge. Twelve
      of the 15 asthmatics reacted with asthmatic symptoms with a median change in FEV1
      of -16.4% when exposed to the allergen, but not to placebo, in the exposure
      chamber. Three patients had only minor symptoms during both chamber exposures and
      experienced no impairment of pulmonary function. Late-phase reactions were less
      frequent (one vs three) after the exposure chamber challenges, as compared to the
      traditional challenges. None of the healthy subjects reacted to the challenges.
      In conclusion, our exposure chamber was able to elicit symptoms in allergic
      subjects, and this ability was obtained with only minor amounts of house-dust
      mite allergen. The described method could prove to be a more physiologically
      relevant model to monitor individual responses to aeroallergens.

PMID- 9284982
TI  - Cross-reactivity of Olea europaea with other Oleaceae species in allergic
      rhinitis and bronchial asthma.
AB  - Cross-reactivity between pollen extracts of four species of Oleaceae was studied:
      olive (Olea europaea), ash (Fraxinus excelsior), privet (Ligustrum vulgare), and
      lilac (Syringa vulgaris). Thus, 51 patients and 13 atopic controls were studied,
      by means of intracutaneous skin tests, histamine-release tests against the four
      extracts, and specific IgE to O. europaea. The proteic content of the four
      extracts was assessed by SDS-PAGE and immunoblotting, and similarity of all the
      extracts studied was observed after electrophoresis and immunodetection. Six
      common bands were found to be responsible for the cross-reactivity, with apparent
      molecular weights of 49.6, 40, 36.7, 19.7, 16.7, and 14 kDa, respectively. The
      cross-reactivity was also corroborated by immunoblotting inhibition and FEIA
      inhibition. The patients had a similar response to the four allergenic extracts
      used, although the response to Olea was greatest. When the patients were compared
      by their geographic origin (northern or southern Spain, according to the
      distribution of areas of olive pollen influence), there were no significant
      differences between the two groups in skin reactivity, but a higher histamine
      release was observed for the four extracts in the southern group, although it was
      significant only for Fraxinus and Ligustrum. This work corroborated the
      practicality of the diagnostic methods used and the cross-reactivity between the
      four species studied, as demonstrated by the different methods used. Therefore,
      we suggest that only O. europaea extract be used in diagnosis and immunotherapy
      in Oleaceae pollen allergy.

PMID- 9284983
TI  - A comparison of three standard methods of identifying mast cells in endobronchial
      biopsies in normal and asthmatic subjects.
AB  - Reported mast-cell counts in endobronchial biopsies from asthmatic subjects are
      conflicting, with different methodologies often being used. This study compared
      three standard methods of counting mast cells in endobronchial biopsies from
      asthmatic and normal subjects. Endobronchial biopsies were obtained from atopic
      asthmatic subjects (n = 17), atopic nonasthmatic subjects (n = 6), and nonatopic
      nonasthmatic control subjects (n = 5). After overnight fixation in Carnoy's
      fixative, mast cells were stained by the short and long toluidine blue methods
      and antitryptase immunohistochemistry and were counted by light microscopy.
      Method comparison was made according to Bland & Altman. The limits of agreement
      were unacceptable for each of the comparisons, suggesting that the methods are
      not interchangeable. Coefficients of repeatability were excellent, and not
      different for the individual techniques. These results suggest that some of the
      reported differences in mast-cell numbers in endobronchial biopsies in asthma may
      be due to the staining method used, making direct comparisons between studies
      invalid. Agreement on a standard method is required for counting mast cells in
      bronchial biopsies, and we recommend the immunohistochemical method, since
      fixation is less critical and the resultant tissue sections facilitate clear,
      accurate, and rapid counts.

PMID- 9284984
TI  - Nonspecific binding of IgE to allergens.
AB  - Nonspecific IgE binding to allergens was observed in testing myeloma IgEs,
      namely, IgE-VL and IgE-PS, chimeric IgE (IgE-JW8), and the recombinant IgE Fc
      epsilon peptide CH1-CH4, in two different immunoassays. This binding was
      concentration-dependent but detectable only at higher IgE concentration. In RAST
      inhibition, IgE-allergen interactions could be reduced by using either matching
      or nonmatching allergens. In order to test whether the nonspecific binding of IgE
      to allergens was due to carbohydrate interaction, myeloma IgEs and the chimeric
      IgE were desialized with neuraminidase. Desialized samples were equally well
      recognized by xenogenic antibodies as native IgEs, but binding of IgE to Fc
      epsilon receptors on basophils was affected by the treatment, as shown in the
      histamine-release assay. Desialization of IgE affected also its binding capacity
      to allergens in RAST: binding of chimeric IgE was reduced, but nonspecific
      binding of myeloma IgE-VL was enhanced. Hence, nonspecific allergen-IgE binding
      may be partly due to a lectin-like interaction, but may depend mostly on the
      tertiary structure of IgE. Thus, nonspecific IgE-allergen interactions might
      present a problem 1) at high IgE concentration, and 2) depend on the grade of
      sialization of IgE, which might affect its conformation. This may explain why
      patients with elevated total IgE levels often have multiple weak positive RASTs
      with non-cross-reactive allergens.

PMID- 9284985
TI  - A 1-year, placebo-controlled, double-blind house-dust-mite immunotherapy study in
      asthmatic adults.
AB  - Thirty-one adult patients with asthma caused by house-dust mites (HDM) were
      included in this placebo-controlled, double-blind study to evaluate the efficacy
      and safety of specific immunotherapy (SIT) with biologically standardized
      extracts of HDM. The specific diagnosis was confirmed by skin prick tests,
      specific IgE, and bronchial provocation tests with HDM allergens. The patients
      were randomized to receive active treatment with extracts of either
      Dermatophagoides pteronyssinus (Dpt) or D. farinae (Dfa) (Alutard SQ, ALK,
      Denmark) or placebo injections. Twenty-three patients completed the study. After
      1 year of treatment, we found a clinically important and significant reduction in
      both asthma medicine consumption (inhaled steroids 38% and beta 2-agonists 46%)
      and symptom score (57%) in the actively treated group, but not the placebo group.
      These findings were confirmed by a significant decrease in skin and bronchial
      sensitivity to HDM in the active group. Additionally, there was a significant
      difference in the patients' scores for effect in favor of the actively treated
      group. Total IgE and specific IgE to HDM showed no significant changes before and
      after treatment for either group. Spirometric lung-function measurements showed a
      significant increase in forced expiratory volume in 1 s (FEV1) from 85% before to
      89% of predicted values after treatment for the actively treated group. Peak-flow
      measurements at home showed no significant changes during the study. It is
      concluded that allergen SIT is an effective treatment in adult patients suffering
      from asthma due to HDM.

PMID- 9284988
TI  - Anaphylaxis to topical bacitracin.

PMID- 9284987
TI  - Occupational asthma caused by fish inhalation.
AB  - Occupational asthma (OA) due to fish inhalation, confirmed by specific bronchial
      challenge (SBC), has not been described as yet in medical literature, as far as
      we know. We describe two patients whose asthma was induced by occupational
      exposure to fish and confirmed by serial measurements of PEFR and SBC. Two fish
      processing workers reported asthma symptoms related to their workplace. They were
      skin tested with fish extracts and their sera assayed for IgE antibodies to
      various fish species. Nonspecific bronchial reactivity was assessed by
      methacholine challenge. The occupational relationship was confirmed by PEFR
      monitoring in working and off-work periods. SBC with fish extracts was carried
      out to confirm the diagnosis of OA. Skin tests with raw and cooked plaice,
      salmon, hake, and tuna in patient 1 and anchovy, sardine, trout, salmon, Atlantic
      pomfret, and sole in patient 2 were positive. Specific IgE serum antibodies were
      found to salmon in patient 1 and to trout, anchovy, and salmon in patient 2. PEFR
      measurements differed significantly (P < 0.001) between work and off-work periods
      for both patients. A bronchial challenge with methacholine was positive in
      patient 1. SBC with raw hake, salmon, plaice, and tuna extracts in patient 1 and
      raw salmon extract in patient 2 were all positive with an immediate response. SBC
      with Dermatophagoides pteronyssinus extract was entirely negative in both
      patients. In three asthmatic, non-fish-allergic controls, SBC with tuna, hake,
      salmon, and plaice were all negative. These results suggest that fish inhalation
      can elicit IgE-mediated occupational asthma.

PMID- 9284986
TI  - Increased allergen-specific Th2 responses in vitro in atopic subjects receiving
      subclinical allergen challenge.
AB  - The study aimed to determine whether inhalation of subclinical allergen doses
      leads to a shift in the balance between T helper (Th) 1 and Th2 cells in
      asthmatic patients. Elevated IgE requires allergen-specific T cells producing
      cytokines such as interleukin (IL)-4 or IL-13. Interferon-gamma (IFN-gamma)
      produced by Th1 cells counteracts the effects of IL-4. In nature, allergic
      persons are often exposed to low levels of allergen, leading to hyperreactivity,
      but not to acute allergic reactions. In this study, nine allergic persons inhaled
      low doses of allergen or placebo in a double-blind manner over seven consecutive
      weekdays. During the study, the bronchial responsiveness to histamine challenge
      increased, but no subject exhibited asthmatic symptoms. Blood was drawn on days
      0, 1, 4, and 9, and the number of IL-4- and IFN-gamma-producing cells was
      measured by enzyme-linked immunospot (ELISPOT) assay after in vitro stimulation
      with a low-dose phytohemagglutinin (PHA) mixed with the relevant allergen or with
      PHA alone. In three of the four subjects receiving allergen, the IL-4/IFN-gamma
      ratio increased during the time of the study. No increase was seen in the placebo
      group. No increase was seen in serum IgE levels in any of the groups. We conclude
      that a shift in the balance between Th1 and Th2 cells can be detected in subjects
      exposed to subclinical allergen doses.

PMID- 9284989
TI  - Sex difference in asthma prevalence.

PMID- 9284990
TI  - Latex allergy correlates with operation.

PMID- 9284991
TI  - Ozone increases group 5 allergen content of Lolium perenne.

PMID- 9284992
TI  - Skin reaction to contrast medium.

PMID- 9284993
TI  - Honey allergy and rhinitis in Ankara, Turkey.

PMID- 9284994
TI  - Anaphylaxis to dexamethasone.

PMID- 9284995
TI  - High resolution protein electrophoresis of equine cerebrospinal fluid.
AB  - OBJECTIVE: To determine normal CSF electrophoresis patterns in horses, and to
      determine whether the electrophoretic scans from horses with cervical compression
      differ from those of neurologically normal horses. ANIMALS: 32 horses assigned to
      1 of 2 groups: neurologically normal (n = 18) or cervical compression (n = 14).
      PROCEDURE: CSF was collected from 18 neurologically normal horses referred to the
      Marion duPont Scott Equine Medical Center, and protein electrophoresis was
      performed to describe the normal equine CSF electrophoretogram. Results of CSF
      electrophoresis from 14 horses with cervical compression were then compared with
      results for the neurologically normal horses. RESULTS: Horses with cervical
      compression had decreased beta-globulin fraction, and 1 or 2 prominent post-beta
      2 peak(s). When the presence of post-beta peaks was used as a diagnostic
      criterion for cervical compression, the test had sensitivity of 71.4% and
      specificity of 81.8%. The positive and negative predictive values were 83.3 and
      69.2%, respectively. CONCLUSION AND CLINICAL IMPLICATIONS: Electrophoresis of CSF
      may be a useful diagnostic aid in evaluation of horses with neurologic disease.

PMID- 9284996
TI  - Ultrasound biomicroscopy of globes from young adult pigs.
AB  - OBJECTIVE: To determine anterior chamber ocular measurements of adult porcine
      globes without histologic fixation by use of ultrasound biomicroscopy scanning.
      SAMPLE POPULATION: 25 porcine globes obtained at an abattoir. PROCEDURE: Globes
      were packed on ice for transport. In the laboratory, globes were trimmed, rinsed
      with antibiotic solution, secured on a single gauze-fold in a latex holder, then
      were ultrasonogrammed unreformed. Ultrasound biomicroscopy scanning was done,
      using a 50-MHz transducer, 17-mm cup, and 2% methyl cellulose. RESULTS: Average
      young adult pig external ocular measurements were: nasal-temporal corneal
      diameter, 16.61 mm; superior-inferior corneal diameter, 14.00 mm; nasal-temporal
      globe diameter, 25.48 mm; superior-inferior globe diameter, 24.48 mm; and axial
      length 21.64 mm. Ultrasound biomicroscopy anterior chamber measurements were:
      iris sulcus, 30.45 degrees; ciliary sulcus, 18.89 degrees; central corneal
      thickness, 0.98 mm; corneal thickness at limbus, 1.19 mm; central iris thickness,
      0.58 mm; iris tip to ciliary apex, 1.73 mm; iris tip to iris sulcus origin, 3.83
      mm; iris tip to ciliary sulcus origin, 2.98 mm; anterior chamber depth from iris
      tip to cornea, 2.21 mm; central anterior chamber depth, 2.47 mm; ciliary process
      mid-thickness, 0.65 mm; ciliary process apex to origin of iris sulcus, 2.32 mm;
      ciliary process apex to origin of ciliary sulcus, 1.34 mm; zonular bundle
      diameter, 0.10 mm; and interzonular bundle space, 0.11 mm. CONCLUSIONS: Anatomic
      anterior chamber measurements and relations in porcine globes can be used to
      describe trauma, confirm existence of lesions, and help explain theory. CLINICAL
      RELEVANCE: Ultrasound biomicroscopy is a clinical decision aid facilitating
      noninvasive anatomic or pathologic description without histologic fixation.

PMID- 9284997
TI  - Variations in the mechanical properties of cartilage from the canine
      scapulohumeral joint.
AB  - OBJECTIVE: To measure the intrinsic material properties of scapulohumeral joint
      cartilage in adult dogs and determine whether regional differences exist within
      or between the humeral and glenoid cartilages. SAMPLES: Paired shoulder joints
      from 7 clinically normal adult dogs. PROCEDURE: An automated indentation
      apparatus was used to obtain the intrinsic mechanical properties of the cartilage
      at 7 sites on each joint surface. RESULTS: Topographic variations in mechanical
      properties of the glenoid and humeral cartilages were observed. The largest
      aggregate modulus (HA) for the humerus was seen at the caudocentral site (0.92
      MPa) and for the scapula was seen at the centrocenter site (0.84 MPa). The mean
      shear modulus (mu) of humeral cartilage (0.23 MPa) was significantly greater than
      that of the glenoid cartilage (0.19 MPa). The mean Poisson's ratio (v) of humeral
      cartilage (0.24) was significantly smaller than that for the glenoid cartilage
      (0.29). Mean humeral cartilage aggregate modulus (0.71 MPa) was larger than the
      value for glenoid cartilage (0.67 MPa), but these differences were not
      significant. There were no significant differences in the compressive stiffness
      of the opposing cartilage in the canine scapulohumeral joint. CONCLUSIONS:
      Differences in mechanical properties between opposing humeral and glenoid
      cartilages are not a cause of cartilage injury in the scapulohumeral joint of
      adult dogs. The mechanical properties of cartilage from young dogs with open
      physes and incomplete subchondral bone plates may be different from those of
      adult dogs.

PMID- 9284998
TI  - Identification of thrombospondin as a high molecular mass protein released from
      activated equine platelets.
AB  - OBJECTIVE: To establish the existence of platelet-derived proteins in equine
      plasma, with the future goal of developing an assay for the detection of in vivo
      platelet activation. ANIMALS: 5 mature healthy horses. PROCEDURE: Platelet-rich
      plasma and platelet-poor plasma were prepared from anticoagulated blood.
      Platelets were separated from plasma proteins by gel filtration, then activated
      with 0.5 microM platelet-activating factor. Protease inhibitors were added, and
      the released platelet proteins were harvested. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis was performed on the released platelet
      proteins and platelet-poor plasma, and the resultant silver-stained bands were
      compared. Immunoblot analysis was performed on released platelet proteins, using
      an antibody to human thrombospondin; human platelet-derived proteins served as
      the positive control for the antibody. RESULTS: Released platelet proteins in the
      presence of beta-mercaptoethanol (reduced samples) contained several proteins
      that were not observed in plasma including (mean +/- SEM) 194 +/- 2, 159 +/- 2,
      151 +/- 2, 104 +/- 2, and 95 +/- 1 kd. Immunoblots of released platelet proteins
      had a prominent 180 +/- 2-kd protein in reduced samples that was recognized by an
      antibody to human thrombospondin, and with prolonged color development, 2
      additional less prominent proteins (166 +/- 1 and 155 +/- 1 kd) were observed.
      CONCLUSIONS: Several proteins are released from activated equine platelets that
      are not detectable in normal equine plasma. Thrombospondin is one of the high
      molecular mass proteins released by activated equine platelets. CLINICAL
      RELEVANCE: An assay can be developed for detection of thrombospondin in equine
      plasma and may be useful for detection of in vivo platelet activation in horses.

PMID- 9284999
TI  - Myoelectric activity of the cecum and proximal loop of the ascending colon in
      cows after spontaneous cecal dilatation/dislocation.
AB  - OBJECTIVE: To analyze myoelectric activity of the cecum and proximal loop of the
      ascending colon (PLAC) in cows after spontaneous cecal dilatation/dislocation
      (CDD) and compare it with that in healthy cows after surgical evacuation of the
      cecum. ANIMALS: 12 cows with spontaneous CDD and 6 healthy cows (group C). Cows
      with spontaneous CDD were retrospectively assigned to 2 groups: delayed recovery
      from surgery or recurrence (group A; n = 3), and normal recovery (group B; n =
      9). PROCEDURE: After surgical evacuation of the cecum, 8 pairs of bipolar,
      retrievable electrodes were implanted in the ileum, cecum, and PLAC. Cows were
      evaluated daily from postoperative day 1 to 7, using routine clinical methods and
      computer-based analysis of myoelectric activity of the cecum, and PLAC.
      Parameters of myoelectric activity included rate of spike bursts, duration of
      individual spike bursts, duration of overall spike burst activity per electrode,
      rate of propagated spike burst sequences, and ratio of orally propagated spike
      burst sequences. RESULTS: Rate of spike bursts, duration of cecocolic spike burst
      activity, and ratio of orally to aborally propagated spike burst sequences did
      not vary among groups during the 7-day recording period. However, cows with
      delayed recovery had a typical, uniform pattern of myoelectric activity of the
      cecum and PLAC at days 1 and 2 after surgery that consisted of repeated,
      propagated spike burst sequences, made up of spike bursts of significantly (P <
      0.05) increased duration at postsurgical day 1 and substantially prolonged
      duration at postsurgical day 2, interrupted by periods of little or no activity.
      CONCLUSION: Delayed recovery and recurrence of CDD in cows after spontaneous CDD
      is not caused by hypomotility of the cecum and PLAC. CLINICAL RELEVANCE:
      Postoperative treatment, intended to reduce recurrence of CDD or delayed recovery
      after surgical evacuation of the cecum, should address propagation of digesta in
      the spiral colon.

PMID- 9285000
TI  - Characterization of cytokine profiles and double-positive lymphocyte
      subpopulations in normal bovine lungs.
AB  - OBJECTIVE: To characterize cytokine profiles and lymphocyte subpopulations in
      lung parenchyma and bronchoalveolar lavage (BAL) fluid from normal bovine lungs.
      ANIMALS: Eight 12- to 18-month-old cattle. PROCEDURE: Cell populations in BAL
      fluid and collagenase-digested lung parenchyma were analyzed by flow cytometry
      and monoclonal antibodies. Proportions of total cell populations were determined,
      using Giemsa-stained cytospots. Distribution of lymphocytes within the lung
      parenchyma was analyzed by immunohistochemistry, and cytokine mRNA species in the
      parenchyma were characterized by use of reverse transcriptase-polymerase chain
      reaction analysis. RESULTS: Cytokine profiles indicated high amounts of mRNA for
      interleukins 6 and 10 and transforming growth factor beta. In the BAL fluid and
      lung parenchyma, macrophages were the predominant cell type, although the
      proportion was lower in the parenchyma. Lymphocytes made up approximately 3% of
      both cell populations. Common to both lung compartments was the predominance of
      CD2+ and gamma delta T cells over B lymphocytes. There were more CD8+ T cells
      than CD4+ T cells in both compartments. The gamma delta cells made up
      approximately 9% of the lymphocyte populations. Two-color flow cytometry revealed
      CD8+ gamma delta T cell and CD8+CD5- populations that were unique to BAL fluid.
      In the BAL fluid and parenchyma, most CD4+ and CD8+ T cells expressed high
      amounts of CD44, a characteristic of memory T cells. The gamma delta T cells were
      CD44(10), as were B cells in the lung parenchyma. The B cells from BAL fluid
      expressed high amounts of CD44. Immunohistologic analysis of lung tissue revealed
      bronchus-associated lymphoid tissue structures with distinctive germinal center
      organization of B cells encompassed by CD4+ T cells. CONCLUSIONS: Results
      provided normal values for comparison with those of other species and with the
      bovine respiratory tract response to disease.

PMID- 9285001
TI  - Field trial to evaluate the immunogenicity of pseudorabies virus vaccines with
      deletions for glycoproteins G and E.
AB  - OBJECTIVE: To evaluate, under field conditions, the immunogenicity of 2
      pseudorabies virus (PRV) vaccines (each with deletion of the gene for
      glycoprotein G [gG], and 1 with an additional deletion for glycoprotein E [gE]),
      particularly in the presence of maternal antibodies, and to investigate the
      effect of vaccination schedules in overcoming maternal antibody interference with
      vaccination. SAMPLE POPULATION: Two cohorts of 105 growing pigs each on a PRV
      seronegative commercial swine farm where breeding stock had been vaccinated with
      a PRV vaccine containing deletions of genes for gG and gE. PROCEDURE: Within each
      cohort, pigs were randomly assigned to 1 of 7 treatment groups. For each vaccine,
      vaccination was done at 8, 12, or 8 and 12 weeks of age. One group remained
      unvaccinated. Blood and nasal swab specimens were obtained at 8, 10, 12, 14, and
      16 weeks of age, and the immune response was measured, by use of an ELISA.
      RESULTS: In cohort 1, where prevalence of maternal antibodies at 8 weeks of age
      was lower, an immune response lasting until 16 weeks of age was induced in most
      pigs by either vaccine. In cohort 2, where prevalence of maternal antibodies at 8
      weeks of age was higher, the gG- gE- vaccine elicited a lower immune response in
      the presence of maternal antibodies than did the gG- vaccine after single
      vaccination at 8 weeks of age. This maternal antibody interference with the
      response to vaccination was evident in serum and nasal mucosal antibodies.
      CONCLUSIONS: The gE deletion decreases the immunogenicity of PRV vaccine in the
      presence of maternal antibodies. Although evidence of maternal antibody
      interference for the gG- vaccine existed, its immunogenicity was diminished less
      in the presence of maternal antibodies than that of the gG- gE- vaccine.

PMID- 9285002
TI  - Comparison of whole-cell antigens of pressure- and formalin-killed Flexibacter
      columnaris from channel catfish (Ictalurus punctatus).
AB  - OBJECTIVE: To identify and compare immunodominant antigens in whole-cell lysates
      of pressure- and formalin-killed Flexibacter columnaris. ANIMALS: Sera from
      naturally infected and vaccinated channel catfish. PROCEDURES: Whole-cell lysates
      of pressure- and formalin-killed F columnaris were compared, and antigens were
      isolated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The
      antigens were identified by staining, western blotting, and specific monoclonal
      antibodies to glycoproteins. Western blotting was performed, using sera from
      channel catfish (Ictalurus punctatus) with naturally acquired F columnaris
      infection and sera from channel catfish vaccinated with an experimental prototype
      F columnaris vaccine. RESULTS: Whole-cell lysates of pressure and formalin-killed
      F columnaris shared 4 proteins: 100, 80, 66, and 60 kd. The 60-kd antigen was a
      glycoprotein. Western blotting, using sera from naturally infected channel
      catfish, revealed the same proteins for pressure- and formalin-killed F
      columnaris. Sera from vaccinated fish reacted only to pressure-killed lysate
      antigens. CONCLUSIONS: Pressure- and formalin-killed F columnaris whole-cell
      lysates share 100-, 80-, 66-, and 60-kd proteins and are recognized by antibodies
      from naturally infected catfish and those vaccinated with formalin-killed F
      columnaris. Formalin treatment modifies or inactivates the 60-kd protein
      antigens, rendering them unrecognizable to antibodies from channel catfish
      naturally infected with F columnaris, suggesting that formalin-killed F
      columnaris may not be suitable for use as a bacterin against columnaris disease.

PMID- 9285003
TI  - Dietary modulation of methotrexate-induced enteritis in cats.
AB  - OBJECTIVE: To determine effects of purified and dry expanded (complex) diets on
      intestinal structure and function in healthy cats and in a feline model of
      methotrexate-induced enteritis. ANIMALS: 19 adult specific-pathogen-free cats.
      PROCEDURE: Cats were randomized in groups to receive a purified diet
      intragastrically or a complex diet orally to meet their daily metabolizable
      energy requirements. After 21 days, cats received either methotrexate (MTX; 10
      mg/kg of body weight, i.v., n = 12) or saline solution i.v. (n = 7), and were
      anesthetized 72 hours later. Celiotomy was performed for aseptic removal of
      mesenteric lymph nodes, full-thickness biopsy of the gastrointestinal tract, and
      collection of aortic and portal venous blood samples for determination of
      arteriovenous amino acid concentrations across the intestine. RESULTS: MTX was
      associated with severe enterotoxicosis in cats receiving the purified diet, as
      manifested by diarrhea (4 of 6 cats) and vomiting (2 of 6 cats). One cat
      receiving the complex diet developed mild diarrhea, and none of these cats
      vomited. The purified diet was associated with marked villus blunting in the
      proximal and distal portions of the duodenum and increased bacterial
      translocation (3 of 6 cats), whereas none of the cats in the complex diet group
      developed bacterial translocation after MTX administration. For the cats given
      saline solution, bacterial translocation occurred in 1 of 4 cats receiving the
      complex diet versus 2 of 3 cats receiving the purified diet. CONCLUSIONS: Feeding
      of a complex diet containing intact protein as the nitrogen source abrogated the
      proximal small intestinal atrophy and bacterial translocation associated with
      feeding an amino acid-based purified diet. CLINICAL RELEVANCE: Use of purified
      diets containing free amino acids as the only nitrogen source cannot be endorsed
      in human and animal cancer patients receiving systemic chemotherapy.

PMID- 9285004
TI  - Use of transabdominal ultrasound-guided amniocentesis for detection of equid
      herpesvirus 1-induced fetal infection in utero.
AB  - OBJECTIVE: To evaluate transabdominal ultrasound-guided amniocentesis for
      detection of equid herpes-virus 1 (EHV-1)-induced fetal infection in utero.
      ANIMALS: 4 Welsh Mountain mares. PROCEDURE: Pregnant mares were inoculated
      intranasally with EHV-1 during the ninth month of gestation. Amniocentesis was
      initiated on postinoculation day (PID) 12, and was performed at 2- to 3-day
      intervals in standing mares under deep sedation. Amniotic fluid samples were
      tested by virus isolation (VI), polymerase chain reaction (PCR), and
      immunoperoxidase cytologic examination (IC) for detection of EHV-1. RESULTS:
      Exposure to EHV-1 in the ninth month of gestation resulted in nasal shedding of
      infective virus, establishment of cell-associated viremia, and seroconversion.
      Equid herpesvirus 1 was detected by VI, PCR, and IC in amniotic fluid collected
      on PID 14 from 1 mare and on PID 16 and 17 from a second mare. Specimens of
      amniotic fluid from a third mare were VI negative until PID 18, when collections
      ceased, although this mare subsequently aborted an EHV-1-infected fetus on PID
      28. The fourth mare aborted an EHV-1 infected fetus on PID 14. The 2 mares with
      VI-positive amniotic fluid were each carrying an EHV-1 infected fetus in utero,
      confirmed by examination of the uterus, placenta, and fetus, using specific
      immunohistochemistry and in situ hybridization. Endothelial cells in the
      endometrium and allantochorion were often virus-infected, with accompanying
      vascular lesions. The fetus had been infected via the chorionic vasculature in
      the first and fourth mares, and by inhalation of infected amniotic fluid in the
      second mare. CONCLUSION: Amniocentesis permits specific detection of EHV-1
      induced fetal infection in utero. CLINICAL RELEVANCE: Amniocentesis may have a
      clinical role in the specific identification and isolation of mares carrying
      virus-infected fetuses during EHV-1-induced abortion epizootics.

PMID- 9285006
TI  - Effects of acute endotoxemia on serum somatotropin and insulin-like growth factor
      I concentrations in prepubertal gilts.
AB  - OBJECTIVE: To evaluate effects of endotoxemia on serum somatotropin (ST) and
      insulin-like growth factor I (IGF-I) concentrations in finishing pigs. ANIMALS:
      Eight female pigs (98 +/- 2 kg) randomly assigned to IV administration (time 0)
      of saline solution (n = 4) or Escherichia coli lipopolysaccharide (LPS; 5
      micrograms/kg of body weight; n = 4). PROCEDURE: Serum ST concentration was
      determined in serum samples obtained at 20-minute intervals for 6 hours after
      treatment. Serum IGF-I concentration was determined in samples collected at 1
      hour intervals for 6 hours and at 12, 15, 18, 24, 48, 72, and 96 hours after
      treatment. RESULTS: One distinct pulse of ST (peak 10.5 +/- 0.5 ng/ml) was
      observed at 40 minutes in each pig after administration of LPS. Control pigs had
      2.25 +/- 0.48 ST pulses during the 6 hours of frequent sample collection;
      however, magnitude of the ST pulses was similar between gilts given LPS and
      control gilts. A temporal association between ST pulses and saline administration
      was not evident. Serum IGF-I concentration was similar between gilts of the LPS
      and control groups prior to treatment. The IGF-I concentration was similar
      between gilts of the LPS and control groups prior to treatment. The IGF-I
      concentration was lower (P < 0.01) in gilts of the LPS group (44 +/- 5 ng/ml)
      than in gilts of the control group (157 +/- 4 ng/ml) at 24 hours. The difference
      in IGF-I concentrations between groups was evident for 96 hours. CONCLUSIONS:
      Immediate release of ST was attributed to stress associated with acute
      endotoxemia and stimulation of the pituitary gland; immune stimulation by LPS may
      have contributed to the changes in IGF-I concentration. Because feed consumption
      was similar between the 2 groups of pigs, suppression of IGF-I concentration for
      96 hours after administration of LPS was attributable to factors in addition to
      transient feed restriction. Thus, acute endotoxemia altered the positive
      association between ST and IGF-I, and provided evidence for a potential mechanism
      of impaired growth in endotoxemic animals.

PMID- 9285005
TI  - Cardiorespiratory and metabolic effects of walking, standing, and standing with a
      splint during the recuperative period from maximal exercise in horses.
AB  - OBJECTIVE: To determine the effects of walking, standing, or standing with a
      splint on 1 forelimb on rate of recuperation of horses after a brief, intense
      bout of exercise. ANIMALS: 6 adult Thoroughbreds (435 to 542 kg). PROCEDURE:
      Horses were preconditioned by exercise on a treadmill to establish a uniform
      level of fitness. Once fit, the treadmill speed causing each horse to exercise at
      120% of its maximal oxygen consumption was determined and was used in simulated
      races at 14-day intervals. Horses were instrumented for collection of arterial
      and mixed venous blood samples for measurement of acid-base status,
      concentrations of metabolites, and cardiopulmonary indices. The horses were
      exercised at a speed inducing 120% of their maximal oxygen consumption until
      fatigued or for a maximum of 2 minutes. Three recuperative interventions were
      evaluated: walking at 1.8 m/s for 30 minutes, then standing for the remainder of
      the 90-minute trial; standing stationary for 90 minutes; and standing stationary
      for 90 minutes with a splint on the right forelimb. RESULTS: Walking
      significantly increased cardiac output during the recuperative phase and hastened
      recovery of normal acid-base status and return of blood lactate concentration to
      baseline values. CONCLUSION: Limiting movement of horses during the recuperative
      period delays recovery from maximal exercise. Most measured indices returned to
      baseline by 60 minutes after exercise. All measured cardiopulmonary indices
      returned to baseline values by 90 minutes after exercise. CLINICAL RELEVANCE:
      Horses that are not allowed to walk during recuperation from exercise may have a
      prolonged recovery period.

PMID- 9285007
TI  - Cardiopulmonary and anesthetic effects of propofol in wild turkeys.
AB  - OBJECTIVE: To determine safety, anesthetic variables, and cardiopulmonary effects
      of i.v. infusion of propofol for induction and maintenance of anesthesia in wild
      turkeys. ANIMALS: 10 healthy, adult wild turkeys. PROCEDURE: Anesthesia was
      induced by i.v. administration of propofol (5 mg/kg of body weight) over 20
      seconds and was maintained for 30 minutes by constant i.v. infusion of propofol
      at a rate of 0.5 mg/kg/min. Heart and respiratory rates, arterial blood
      pressures, and arterial blood gas tensions were obtained prior to propofol
      administration (baseline values) and again at 1, 2, 3, 4, 5, 10, 15, 20, 25, and
      30 minutes after induction of anesthesia. All birds were intubated immediately
      after induction of anesthesia, and end-tidal CO2 concentration was determined at
      the same time intervals. Supplemental oxygen was not provided. RESULTS: Apnea was
      observed for 10 to 30 seconds after propofol administration, which induced a
      decrease in heart rate; however, the changes were not significant. Compared with
      baseline values, respiratory rate was significantly decreased at 4 minutes after
      administration of propofol and thereafter. Systolic, mean, and diastolic
      pressures decreased over the infusion period, but the changes were not
      significant. Mean arterial blood pressure decreased by 30% after 15 minutes of
      anesthesia; end-tidal CO2 concentration increased from baseline values after 30
      minutes; PO2 was significantly decreased at 5 minutes after induction and
      thereafter; PCO2 was significantly (P < 0.05) increased after 15 minutes of
      anesthesia; and arterial oxygen saturation was significantly (P < 0.05) decreased
      at the end of anesthesia. Two male turkeys developed severe transient hypoxemia,
      1 at 5 and the other at 15 minutes after induction. Time to standing after
      discontinuation of propofol infusion was 11 +/- 6 minutes. Recovery was smooth
      and unremarkable. CONCLUSION: Propofol is an effective agent for i.v. induction
      and maintenance of anesthesia in wild turkeys, and is useful for short procedures
      or where the use of inhalational agents is contraindicated.

PMID- 9285008
TI  - Effect of combined staphylectomy and laryngotomy on upper airway mechanics in
      clinically normal horses.
AB  - OBJECTIVE: To investigate the effect of combined staphylectomy and laryngotomy on
      upper airway mechanics in clinically normal horses running on a treadmill.
      ANIMALS: 6 Standardbreds. PROCEDURE: Upper airway mechanics were measured with
      horses trotting or pacing on a treadmill at 5, 8, and 10 m/s before and 6 weeks
      after combined staphylectomy and laryngotomy. Pharyngeal and tracheal inspiratory
      and expiratory pressure were measured by use of transnasal tracheal and
      pharyngeal side hole catheters connected to differential pressure transducers. A
      pneumotachograph mounted on the rostral end of an airtight face mask was used to
      measure airflow. RESULTS: Upper airway and translaryngeal inspiratory impedances
      were higher, respiratory rate was decreased, and inspiratory time was longer (P <
      0.05) at all speeds after staphylectomy and laryngotomy. CONCLUSION: Combined
      staphylectomy and laryngotomy significantly affects upper airway mechanics in
      clinically normal horses. CLINICAL RELEVANCE: Because combined staphylectomy and
      laryngotomy exerts a potentially adverse effect on upper airway mechanics in
      clinically normal horses, the procedure should only be performed when it is
      clearly indicated.

PMID- 9285009
TI  - Effects of bilateral hypoglossal and glossopharyngeal nerve blocks on epiglottic
      and soft palate position in exercising horses.
AB  - OBJECTIVE: To determine the effect of bilateral hypoglossal and and
      glossopharyngeal nerve block on epiglottic and soft palate position and tracheal
      and pharyngeal pressures in exercising horses. ANIMALS: 5 Standardbreds.
      PROCEDURE: Tracheal and pharyngeal pressures were measured in 5 Standardbreds
      exercising at the speed at which the horses achieved 50, 75, and 100% of maximal
      heart rate after bilateral hypoglossal and glossopharyngeal nerve block and
      without nerve block. Nerve block was achieved by injection of 1 to 2 ml of 2%
      mepivicaine hydrochloride between the glossopharyngeal and hypoglossal nerves, as
      they coursed through the medial compartment of the diverticulum of the auditory
      tube (guttural pouch), using videoendoscopic guidance and an injection apparatus.
      RESULTS: Compared with control values, peak inspiratory tracheal pressure was
      significantly (P = 0.02) more negative, and peak pharyngeal inspiratory pressure
      was less negative (P = 0.004) after bilateral hypoglossal and glossopharyngeal
      nerve block. Respiratory frequency was significantly (P = 0.024) lower after
      nerve block, compared with control values. The epiglottis was unstable and
      retroflexed through the rima glottis during inspiration after bilateral
      hypoglossal and glossopharyngeal nerve block. Despite loss of contact between the
      epiglottis and the caudal free margin of the soft palate, dorsal displacement of
      the soft palate did not occur. CONCLUSIONS AND CLINICAL RELEVANCE: Loss of
      contact of the epiglottis with the soft palate did not affect soft palate
      position, suggesting that when the soft palate is normal, the epiglottis does not
      function as a support, holding the soft palate in a ventral position. Therefore,
      epiglottic dysfunction is not solely responsible for intermittent dorsal
      displacement of the soft palate in horses, and neuromuscular dysfunction
      involving the hyoepiglotticus muscle, geniohyoideus muscle, or the hypoglossal
      nerve may cause epiglottic retroflexion in horses.

PMID- 9285010
TI  - Synovial fluid interleukin 6, tumor necrosis factor, and nitric oxide values in
      dogs with osteoarthritis secondary to cranial cruciate ligament rupture.
AB  - OBJECTIVE: To measure and compare values of interleukin 6 (IL-6), tumor necrosis
      factor (TNF), and nitric oxide (NO) metabolites in synovial fluid from canine
      joints with osteoarthritis (OA) secondary to naturally acquired cranial cruciate
      ligament (CCL) rupture and experimental CCL transection. ANIMALS: 57 dogs
      (clinical group) with OA secondary to CCL rupture; 5 dogs (experimental group)
      with OA secondary to CCL transection; 19 control dogs with normal joints.
      PROCEDURE: Joints were radiographed and graded for seventy of OA. Synovial fluid
      was collected from dogs: at surgery from the clinical group, at 90 days after
      surgery from the experimental group, and at necropsy from the control group.
      Activities of IL-6 and TNF, as well as concentration of the NO metabolites (NO2
      /NO3-) were measured, and results were reported as mean +/- SEM. RESULTS: IL-6
      activity in dogs of the clinical (290 +/- 40 U/ml) and experimental (494 +/- 165
      U/ml) groups was greater than that in control dogs (6 +/- 1.6 U/ml; P < 0.05).
      The TNF values in dogs of the clinical (3.0 +/- 0.5 pg/ml) and experimental (2.0
      +/- 0.9 pg/ml) groups were lower than those in control dogs (8.6 +/- 2.3 pg/ml; P
      < 0.05). The IL-6 values were negatively associated with radiographic score of OA
      and were positively associated with age (R2 = 26.5%, P < 0.05). CONCLUSION: Dogs
      with OA secondary to naturally acquired CCL rupture and experimental CCL
      transection had significantly different alterations in synovial fluid IL-6 and
      TNF values. The decrease in IL-6 activity with advancing OA was independent of
      the increase in IL-6 activity with aging. CLINICAL RELEVANCE: IL-6 and TNF may be
      involved in pathogenesis of OA secondary to naturally acquired and experimentally
      induced CCL rupture.

PMID- 9285011
TI  - Effect of combined administration of insulin-like growth factor and platelet
      derived growth factor on the regeneration of transected and anastomosed sciatic
      nerve in rats.
AB  - OBJECTIVE: To evaluate the efficacy of combined administration of platelet
      derived growth factor (PDGF) and insulin-like growth factor (IGF-I) on the
      regeneration of transected and anastomosed sciatic nerves. ANIMALS: 25 male Lewis
      rats. PROCEDURE: Transection and anastomosis was performed of the left sciatic
      nerve of all rats. At the time of surgery, treatment group rats received a
      combination of PDGF (0.75 microgram) and IGF-I (1.5 micrograms) along with
      vehicle (2% methyl cellulose gel) at the anastomosis site. Control rats received
      vehicle alone. Evaluation consisted of motor evoked potentials and nerve
      conduction velocity, quantitative histologic examination, sciatic functional
      index, and visual assessment of repair organization (lesion scores). RESULTS:
      Significant differences in motor evoked potential latency, nerve conduction
      velocity, axon number, sciatic functional index, or lesion scores were not found
      between groups. CONCLUSIONS: Combined administration of PDGF and IGF-I did not
      enhance peripheral nerve regeneration in a transection and anastomosis model as
      determined 6 weeks after surgery. CLINICAL RELEVANCE: These findings support the
      assumption that mechanical, versus trophic, effects predominate when nerve ends
      are closely apposed.

PMID- 9285012
TI  - Comparison of effects of albendazole sulfoxide on in vitro produced bovine
      embryos and rat embryos.
AB  - OBJECTIVE: To evaluate and compare effects of albendazole sulfoxide (ABZSO) on
      rat embryos and bovine embryos produced in vitro. ANIMALS: In vitro produced
      bovine embryos. Rat embryos recovered from naturally bred Sprague-Dawley rats.
      PROCEDURE: 4- and 8-cell bovine embryos were randomly allocated to ABZSO or
      vehicle control groups. After 48 hours, embryos were evaluated for cell number
      and blastomere morphology. Rat embryos of similar stages, flushed from the
      uterine tube on gestational day 2-5, were randomly allocated to treatment or
      control groups. After 24 hours, embryos were evaluated as described previously.
      RESULTS: 44% of control bovine embryos divided in culture (> or = 16-cell stage).
      Fifteen percent of the controls had morphologic abnormalities, including
      disparity in blastomere size and cytoplasmic vacuoles and stippling. Treated (>
      or = 1 microgram of ABZSO/ml) bovine embryos differed (P < 0.0001) from controls,
      with 4% development and 93% abnormal morphology. Forty-five percent of control
      rat embryos divided in culture. Treated (> or = 500 ng of ABZSO/ml) rat embryos
      differed (P < 0.0003) from controls with regard to ability to divide. There were
      no consistent morphologic abnormalities in rat embryos. CONCLUSIONS: In vitro
      produced bovine embryos were susceptible to ABZSO at a concentration > or = 1
      microgram/ ml, resulting in decreased ability to divide and presence of gross
      morphologic abnormalities. Rat embryos produced in vivo and exposed in vitro to
      ABZSO at a concentration > or = 500 ng/ml had decreased ability to divide in
      culture. CLINICAL RELEVANCE: Despite severe effects of ABZSO (> or = 1
      microgram/ml) on bovine embryo development in vitro, it is beyond the scope of
      this study to speculate whether a therapeutic dosage of albendazole (10 mg/kg of
      body weight) would result in necessary concentrations of ABZSO in vivo to disrupt
      embryogenesis.

PMID- 9285013
TI  - The combined Singapore-Malaysia Congress of Medicine.

PMID- 9285014
TI  - Prevention of falls in a geriatric ward.
AB  - Falls occurring in the hospital are significant events because of the injuries
      sustained, extended hospital stay and potential medicolegal implications. We
      conducted a 3-year study to determine the characteristics of fallers in a
      geriatric ward and assess the effectiveness of lectures and nursing assessments
      in the prevention of falls. In the first year of the study we found that the rate
      of falls was 9% of all patients admitted. About 85.7% of falls occurred at the
      bedside and 41.4% happened while getting in and out of bed. Most falls occurred
      between 4 pm and 8 pm and half of the fallers had no preceding symptoms. In the
      second year, a series of lectures and educational material were given to the same
      nursing staff and the prevalence of falls was reduced to 7% (P > 0.05). However,
      the implementation of a nursing assessment protocol in the third year of the
      study achieved a marked reduction in prevalence of falls to 5.9% from the initial
      9% (Chi-square chi 2 = 4.19, P = 0.04). Thus, the vigorous administration of a
      nursing assessment protocol can reduce falls in a geriatric ward.

PMID- 9285015
TI  - Cognitive testing of elderly Chinese from selected community clubs in Singapore.
AB  - The aim of this study was to describe the psychometric performance of cognitively
      normal elderly Chinese on selected psychological tests. One hundred and fifty
      five community-living, cognitively intact elderly Chinese, stratified according
      to age and gender were administered a selected neuropsychological assessment
      battery which comprised the Abbreviated Mental Test (AMT), the Chinese Mini
      Mental Status (CMMS), the Short Blessed Test (SBT), the Word-List Immediate
      Memory (WL-i), the Word-List Delayed Memory (WL-d), the Word-List Recognition
      Memory (WL-r), the Set Test (ST), the modified Boston Naming Test (BNT), the
      Constructional Praxis Test (CPT), the Block Design Test (BDT) and the Object
      Assembly Test (OAT). The local median scores (ranges) of the above tests were as
      follows-AMT: 9 (6-10); CMMS: 25 (16-28); SBT: 2 (0-10); WL-i: 17 (8-27); WL-d: 5
      (0-10); WL-r: 9 (1-10); ST: 13 (6-25); BNT: 14 (10-15); CPT: 1 (0-3); BDT: 19 (0
      42); OAT: 20 (3-33). These results can assist in the clinical identification of
      cognitive abnormalities amongst the elderly Chinese in Singapore. Future work
      will attempt to adjust these overall scores for variables such as the subjects'
      education and age.

PMID- 9285016
TI  - Systemic lupus erythematosus: initial manifestations and clinical features after
      10 years of disease.
AB  - We studied the initial manifestations and late features in our lupus patients.
      The clinical data of patients fulfilling the American College of Rheumatology
      criteria for systemic lupus erythematosus (SLE) were entered prospectively for
      newly diagnosed patients and cumulatively for those with at least 10 years of
      disease duration. Ninety-seven Group A (newly diagnosed; 86 females and 11 males;
      mean age 31 years; 83 Chinese, 11 Malays, and 3 Indians) and 58 Group B (more
      than 10 years disease duration; 56 females and 2 males; mean age 41 years; 50
      Chinese, 5 Malays, and 3 Indians) lupus patients were studied. The commonest
      clinical features in Group A were: haematological (73%), arthritis (57%), malar
      rash (43%), renal disorder (31%) and photosensitivity (30%). Group B patients had
      haematological (78%), malar rash (73%), arthritis (69%), renal disorder (59%) and
      photosensitivity (33%). Renal disorder was significantly increased over the years
      (P < 0.001). Hypertension was present in 18% (Group A) and 59% (Group B) (P <
      0.00001), diabetes mellitus in 5% (Group A) and 10% (Group B) (P = ns),
      atherosclerosis in 2% (Group A) and 7% (Group B) (P = ns). Cataract formation was
      not present in Group A patients but was present in 10% of Group B patients. Renal
      disorders and morbidity factors like hypertension and cataracts increased
      significantly over the years. Optimum treatment of lupus patients should
      therefore include close attention to these factors.

PMID- 9285017
TI  - Initial construct cross-cultural validation of the Short Form 36 for quality of
      life assessment of systemic lupus erythematosus patients in Singapore.
AB  - The objective of this study was to determine if the Short Form 36 (SF-36) Health
      Survey Questionnaire measures differences in quality of life between lupus
      patients and healthy controls in Singapore. A cross-sectional pilot study was
      conducted on consecutive English-speaking, female Chinese lupus patients seen at
      a Rheumatology unit. Healthy volunteers were recruited as controls during the
      same time period. All subjects completed the United Kingdom version of the SF-36.
      Lupus disease activity was assessed using the British Isles Lupus Assessment
      Group (BILAG) index and converted to a global score. Lupus-related damage was
      measured using the Systemic Lupus International Collaborating Clinics/American
      College of Rheumatology Damage Index (SLICC/ACRDI). The main outcomes measured
      were the mean SF-36 scale scores for lupus patients and healthy controls. Thirty
      six lupus patients and 76 controls were included in the study. All subjects were
      English-speaking, Chinese female between 21 and 53 years of age. The mean age of
      patients and controls was 31.9 and 29.0 years respectively. Lupus patients had
      lower mean scale scores than controls for physical functioning (73.0 versus 89.7,
      P < 0.0027), bodily pain (71.0 versus 81.4, P < 0.027), physical role functioning
      (55.7 versus 89.5, P < 0.0001) and general health (47.4 versus 51.8, P < 0.05).
      Mean scale scores for vitality, social and emotional role function and mental
      health were similar in both groups. Ten patients had active disease (BILAG global
      scores of 3 to 14) and 13 patients had lupus-related damage (Damage Index scores
      of 1 to 7). These preliminary data suggest that the SF-36 Health Survey may be
      able to measure differences in quality of life between lupus patients and healthy
      controls in Singapore.

PMID- 9285018
TI  - Delays in thrombolytic therapy in acute myocardial infarction: an audit from the
      east coast of peninsular Malaysia.
AB  - The objectives of this study were to evaluate the time delays between the onset
      of symptoms and admission to hospital and provision of thrombolytic therapy in
      patients with suspected acute myocardial infarction; and to examine the accuracy
      of the clinical diagnosis and the therapeutic decision on thrombolysis in these
      patients. An observational study of 96 patients with suspected myocardial
      infarction was undertaken over a period of 15 months in the Coronary Care Unit of
      Hospital Kuala Terengganu. Seventy per cent of the patients arrived in the
      hospital within 6 hours of the onset of symptoms. After arrival in the emergency
      room, it took a median time of 85 minutes before the administration of
      thrombolytic therapy. Of the 67 patients who were given thrombolysis, 46 were
      treated within 6 hours of the onset of symptoms. About a quarter of patients said
      that they had delayed seeking treatment at the hospital. Treatment delays
      occurring in the hospital were mainly due to admission procedures as well as late
      diagnosis. Eighty-one patients had confirmed myocardial infarction of whom 59
      received thrombolytic therapy. Eight patients receiving thrombolytic therapy had
      no confirmation of myocardial infarctions. Improvements in diagnostic accuracy
      and reduction of delays in the provision of thrombolytic therapy could be
      achieved by better training of health care staff as well as by further
      streamlining of admission procedures.

PMID- 9285019
TI  - Infections in paediatric renal transplant recipients.
AB  - A retrospective study of all children who had undergone renal transplantation at
      the National University Hospital was undertaken in order to investigate the types
      and frequency of infections in paediatric renal transplant recipients. A total of
      13 children ranging in age from 3 to 17 years were transplanted over a 7-year
      period from 1989 to 1996. The mean follow-up period was 40.5 months. Ten patients
      (77%) had at least one episode of infection post-transplant, 70% of which
      occurred within the first 6 months post-transplant. These infections included
      urinary infections (8), disseminated cytomegalovirus (CMV) disease (4),
      Pneumocystis carinii pneumonia (1) and mycoplasma pneumonia (1). Urinary tract
      infections were significantly associated with the presence of ureteral stents.
      CMV disease was significantly associated with the use of mycophenolic acid in the
      early post-transplant period. Infection therefore continues to be a major cause
      of morbidity in paediatric renal transplant recipients.

PMID- 9285021
TI  - Biofeedback therapy for bowel dysfunction following low anterior resection.
AB  - Faecal incontinence and intractable constipation after low anterior resection
      (LAR) can be refractory to expectancy and appropriate anti-diarrhoeal or laxative
      medications. The efficacy of anorectal biofeedback therapy (BF) in this clinical
      situation was prospectively assessed. Eleven patients [5 men and 6 women; mean
      age 64.8 years; standard error of the mean (SEM) 3.3 years] had either faecal
      incontinence or intractable constipation which did not settle with medications,
      for at least 6 months [mean 33.3 (SEM 6.1) months] after LAR. They all underwent
      4 sessions of outpatient BF. Assessment was by continence questionnaire and
      anorectal physiology tests, which were administered before and after BF. In 6 of
      6 incontinent patients, weekly incontinent episodes were decreased [14.8 (SEM
      2.1] before, 1.8 (SEM 0.8) after; P < 0.05) and anti-diarrhoeal drug requirements
      were reduced (needed in 6 before, 0 after; P < 0.05) after BF. In the 5
      intractible constipation patients, the weekly stool frequency was improved [3
      (SEM 0.5) before, 8.9 (SEM 1.6) after; P < 0.05] after BF. There were no
      significant changes in the anorectal physiology parameters after BF. At a mean
      follow-up of 12.9 (SEM 1.6) months, there were no regressions or complications.
      BF is a safe option for refractory bowel dysfunction following LAR.

PMID- 9285020
TI  - Presence of domestic pets and respiratory symptoms in asthmatic children.
AB  - The allergens of domestic pets such as cats, dogs and birds, have been known to
      sensitive predisposed individuals. In Singapore, approximately 25% to 35% of our
      atopic populations are sensitised to cat, dog or bird feather allergens. It is
      not known, however, if the presence of such domestic pets would translate to
      higher rates of sensitisation, or more importantly, give rise to increased
      respiratory symptoms. This study evaluated the association between the presence
      of domestic pets at home and the prevalence of respiratory symptoms among
      asthmatic children in Singapore. The parents of 1517 doctor-diagnosed asthmatic
      children were interviewed using the American Thoracic Society-Division of Lung
      Diseases respiratory questionnaire. More than 20% were found to have domestic
      pets (cats, dogs or birds) at home. Of these, those with exposure to passive
      smoke in the home were excluded. A total of 188 current pet owners (cats, dogs
      and birds) were demographically-matched for sex, race and socio-economic status
      (type of housing) to those without pets, past or current. Compared to those
      without pets, asthmatic children with pets at home had a higher prevalence of
      coughing with cold [relative risk (RR) 1.30; 95% confidence interval (CI) 1.01 to
      1.69]; wheezing with cold (RR 1.42; CI 1.07 to 1.90), wheezing with shortness of
      breath (RR 1.33; CI 1.00 to 1.82), exercise-induced wheezing (RR 1.68; CI 1.10 to
      2.56); and increased phlegm production or congestion with cold (RR 1.38; CI 1.00
      to 1.91). This study suggests that the presence of domestic pets increases the
      prevalence of respiratory symptoms in asthmatic children. Those with
      predisposition to these allergens should avoid having these pets in the home or
      take specific precautions in avoiding their allergens.

PMID- 9285022
TI  - Plasma lipids and lipoprotein(a) levels in the Chinese from China and Singapore.
AB  - This study compared the influence of environmental factors on plasma lipid levels
      between the descendants of immigrant southern Han Chinese (Singapore Chinese, n =
      275) and the native Chinese from southern China (n = 277). Their lipid profiles
      including lipoprotein (a) [Lp(a)] were measured and compared. The alpha level was
      set at 0.05 throughout the analysis. Body mass index (BMI), plasma total
      cholesterol (TC), low density lipoprotein cholesterol (LDLC), high density
      lipoprotein cholesterol (HDLC) and triglycerides (TG) levels were significantly
      elevated in the Singapore Chinese. Plasma Lp(a) however, was comparable in both
      groups for concentrations as well as frequency distributions. Since both groups
      were genetically identical, the similar Lp(a) level was in agreement with studies
      which reported that the apolipoprotein(a) [apo(a)] gene explained as much as 70%
      of the plasma Lp(a) variations in Chinese. No correlation of plasma Lp(a) level
      was observed with age and BMI while significant positive linear correlations were
      observed with TC and LDLC in the male subjects only. We concluded that
      environmental factors (possibly affluent lifestyle and westernised diet) have
      significantly influenced the lipid risk factor levels of the Singapore Chinese
      whereas Lp(a) levels, which are predominantly under genetic control, were not
      altered significantly.

PMID- 9285023
TI  - Comparison of peripheral blood CD34+ concentration, colony-forming units
      granulocyte-macrophage and mononuclear cells in leukapheresed product for the
      prediction of peripheral blood CD34+ cell yield harvest.
AB  - The aim of this study was to evaluate reliability of parameters which may be used
      to guide peripheral stem cell harvests in cancer patients prior to myeloablative
      chemotherapy. Each leukapheresed product was analysed for CD34-positive (CD34+)
      cell count, mononuclear cell (MNC) count and the number of colony-forming units
      granulocyte-macrophage (CFU-GM). Each patient's peripheral blood (PB) taken
      before leukapheresis was analysed for CD34+ concentration. We evaluated whether
      the CD34+ yield from leukapheresis correlated with any of the three parameters. A
      total of 119 procedures were performed in 33 patients. The yield of CD34+ cells
      by leukapheresis correlated weakly but significantly with the peripheral blood
      CD34+ cell count (R = 0.4 P < 0.05), the MNC cells (R = 0.4, P < 0.05), and CFU
      GM (R = 0.4, P < 0.05). When a PB CD34+ count of 50 x 10(6)/L was used as a cut
      off value, the accuracy for prediction of adequate leukapheresis (> 1 x 10(6)
      CD34+ cells/kg) was 78%.

PMID- 9285024
TI  - Variants of chromosome 9 in phenotypically normal individuals.
AB  - The human chromosome 9 displays the highest degree of structural variability.
      Four different types of variants are described including pericentric inversion,
      extra G-positive band in the q arm, additional G-positive band in the p arm and
      duplication of band 9q21-q22. It is important to demonstrate inheritance from a
      phenotypically normal individual in order to differentiate between a variant
      chromosome and an abnormal chromosome.

PMID- 9285025
TI  - Molecular studies of loss of heterozygosity in retinoblastoma.
AB  - Retinoblastoma (Rb) is a paediatric intraocular tumour in which predisposition
      can be inherited. Cases of Rb tumours can be divided into three types: familial
      cases, sporadic bilateral cases and sporadic unilateral cases. Familial and
      sporadic bilateral cases are usually categorised as hereditary while sporadic
      unilateral cases as non-hereditary. In both familial and non-familial forms of
      Rb, loss of heterozygosity of the Rb locus has been reported although its
      frequency in tumours has not so far been accurately determined. The cloning of
      the gene responsible for retinoblastoma (Rb1) has facilitated DNA studies and
      genetic counselling of patients. We have examined forty-five cases of
      retinoblastoma at five intragenic sites of the Rb1 locus, namely intron 1/BamH1,
      intron 17/Xba1, intron 24/TthIII1, intron 25/Dra1 and Rb1.20 VNTR. Thirty-six out
      of the forty-five cases (80%) were informative for these markers. Comparison of
      results between genomic DNA from peripheral blood and from tumours revealed that
      loss of heterozygosity of alleles could be detected in 50% of cases studied in
      which tumour samples were available. Investigation of parental origin of retained
      alleles showed that in all these cases, the paternal alleles were preferentially
      retained. The analysis of the genetic origin of mutations predisposing to
      retinoblastoma can facilitate new approaches for identifying recessive mutant
      genes that lead to cancer as well as to provide a conceptual basis for accurate
      prenatal predictions of cancer predisposition.

PMID- 9285027
TI  - Non-insulin dependent diabetes--the past, present and future.
AB  - Diabetes, known since antiquity, has been defined by glycosuria. In 1886, when
      Minkowski demonstrated that pancreatectomized dogs developed diabetes, the islets
      of Langerhans became a focus of the search for an active principle culminating in
      the discovery and the isolation of insulin in 1921 by Banting, Best and Collip.
      In 1959, the radioimmunoassay of Yalow and Berson solidified the concept of
      insulin resistance in non-insulin dependent diabetes (NIDDM). In 1971, the
      insulin receptor was defined as a cell surface protein that initiated the insulin
      signal transduction cascade. Today, we know that NIDDM accounts for at least 90%
      of all diabetes worldwide and involves approximately 100 million people. The
      microvascular complications of NIDDM are the same as for insulin dependent
      diabetes (IDDM) and are related to the intensity and duration of hyperglycaemia.
      Further, it is clear from the Diabetes Control and Complications Trial (DCCT)
      that all microvascular complications can be reduced with intensive control of the
      blood glucose. Macrovascular disease is also accelerated in NIDDM, including both
      hypertension and dyslipidemia. The major risk factor for NIDDM are age, obesity,
      physical inactivity, and genetic background. The earliest features seen in
      individuals destined to develop NIDDM is insulin resistance, but for
      hyperglycaemia to ensure there must be a defect in insulin secretion. Thus,
      insulin resistance defines the prehyperglycaemic phase of NIDDM, but varying
      degrees of insulin secretory deficiency define the hyperglycaemic phase.
      Macrovascular risk occurs throughout the lifetime of the individual, whereas
      microvascular risk ensues with the inception of hyperglycaemia. Tomorrow, we will
      understand more clearly whether lifestyle changes, such as diet and exercise, or
      new classes of drugs, can delay or prevent NIDDM. Clinical trials are now
      beginning to test whether impaired glucose tolerance (IGT) can be delayed or
      prevented from moving to overt NIDDM. The genetics of NIDDM are under intense
      study. Mutations in the insulin receptor lead to NIDDM in a small number of
      patients, and mutations in the glucokinase gene lead to maturity onset diabetes
      of the young (MODY). Work is now underway to study other candidate genes as well
      as work on positional cloning techniques to identify diabetes genetic loci. The
      hormone Leptin has just been discovered and is a major regulator of body weight.
      In summary, the most important new emphasis on the treatment of NIDDM is the
      recognition of the importance of hyperglycaemia and our ability to both treat and
      possibly prevent this metabolic perturbation. This joins the longer-term emphasis
      on cardiovascular risk reduction from both treatment and prevention of
      hypertension and dyslipidemia.

PMID- 9285026
TI  - Safety and efficacy of acellular pertussis vaccines: the Mainz study and other
      recent studies.
AB  - Following concerns about the safety and reactogenicity profile of diphtheria,
      tetanus and whole cell pertussis vaccines (DTwP), new and less reactogenic
      alternatives were developed over the last two decades. The new diphtheria,
      tetanus and acellular pertussis vaccines (DTaP) no longer consist of the whole
      bacterial cell but of either extracts or of a few highly purified components.
      While it soon became clear that DTaP vaccines are significantly less reactogenic
      than DTwP vaccines, their efficacy was disputed and remained unproven. First
      studies and epidemiological data from Japan suggested vaccine efficacy rates (VE)
      of about 80%; however, the first blinded clinical trial from Sweden documented a
      much lower VE. Worldwide, seven large DTaP efficacy trials have recently been
      completed. Our own efforts included a large safety trial with 22505 vaccinees
      and, nested in this setting, a prospective household contact study. Typical WHO
      defined pertussis developed in 7 of 112 DTaP vaccinated children following
      household exposure as compared to 96 cases in 173 children not vaccinated against
      pertussis. Thus, vaccine efficacy was calculated to be 88.7% (95% CI 76.6 to
      94.6). The median duration of spasmodic cough in the few children vaccinated with
      DTaP who did start coughing was 17 days as compared to 35 days in unvaccinated
      children. No waning of protection was observed. None of the confounding variables
      analyzed influenced study results in favour of DTaP. Following administration of
      more than 67000 DTaP doses, 153 serious adverse events were reported. Eight
      events were considered possibly related and five were considered related to the
      study vaccine. According to additional study results from the other trials it can
      be concluded that DTaP vaccines, like DTwP vaccines, are safe and effective. The
      choice between DTwP and DTaP should be based on acceptance of the reactogenicity
      profile, coverage rates achieved, costs and other factors in each individual
      country.

PMID- 9285028
TI  - Prevention of infection in the immunocompromised.
AB  - Infection is an important cause of morbidity and mortality in immunocompromised
      patients. The high risk of infection is not only the consequence of the
      underlying disease but also the result of the diagnostic, monitoring and
      therapeutic procedures performed on these patients. Infections may be exogenous
      or endogenous in origin. The prevention of exogenous infections requires a high
      standard of hygiene. As many infections are acquired in hospitals, an effective
      control of nosocomial infection programme is crucial in preventing infections in
      the immunocompromised. Prevention of endogenous infections involves suppression
      of the aerobic bacterial flora (selective decontamination) and measures to
      maintain gastrointestinal epithelial integrity to reduce risk of translocation of
      intestinal flora. Boosting the host immunity through passive and active
      immunisation should also be considered. Prevention of infection in the
      immunocompromised is no easy task and requires a multidisciplinary approach.

PMID- 9285029
TI  - Adrenal and renal surgery by the laparoscopic and/or retroperitoneoscopic
      approach.
AB  - Since its introduction 6 years ago, almost all abdominal procedures have been
      attempted laparoscopically. Despite their retroperitoneal location, kidneys and
      adrenals have also been reached by the blitz of endoscopic surgery since 1992. We
      present here the techniques, indications, advantages or disadvantages of the
      videoscopic approach-either laparoscopic or retroperitoneoscopic- of those solid
      retroperitoneal organs. Preliminary results of the international literature are
      presented, while objectively comparing currently available data about the
      efficacy and cost of endoscopic versus open procedure. Despite the time-consuming
      nature and high operative cost of the endoscopic approach, decreased
      convalescence and better patient comfort are evident. Furthermore videoendoscopic
      adrenal surgery performed, even sporadically, by surgeons experienced in
      laparoscopic surgery is as safe as the open approach, provided that those
      surgeons are also familiar with the rules and potential drawbacks of adrenal
      surgery for endocrine disorders.

PMID- 9285030
TI  - The use of metallic stents in the palliation of inoperable oesophageal carcinoma.
AB  - Carcinoma of the oesophagus is the seventh most common malignancy worldwide. It
      is a disease with a poor prognosis; more than half of the patients present with
      surgically irresectable tumours. For such patients, palliative therapy is
      directed towards the relief of dysphagia. Expandable metallic stents have
      recently been developed for use in the oesophagus. These have the advantage of
      being introduced through small diameter delivery catheters. Once released, they
      can expand to as much as 25 mm in diameter, potentially allowing patients to
      consume a normal diet. The current designs of metallic stents include the
      Strecker stent, the Wallstent endoprosthesis, and the Gianturco-Rosch stent. The
      Strecker is an uncovered stent while the other two are covered on the outside of
      the stent with plastic to prevent tumour ingrowth. A review of the literature
      indicates that deployment of these stents is associated with a high technical
      success rate. Improvement in swallowing function is seen in 83% to 100% of these
      patients. The overall complication rates are low. However, covered stents are
      prone to migration while uncovered stents are vulnerable to tumour ingrowth.
      Further improvements in design promise to expand the role of these endoprostheses
      in the management of oesophageal carcinoma.

PMID- 9285031
TI  - Exploring the human brain using single-unit microelectrode technique during awake
      stereotactic functional neurosurgery.
AB  - In neuroscience research, the use of true single-unit microelectrode technique
      has been confined largely to the animal neurophysiology laboratory due to the
      complexity of the equipment required and the fastidious, time-consuming nature of
      the methodology. We report here our successful clinical use of this technique in
      human patients with Parkinson's disease undergoing awake stereotactic movement
      disorder neurosurgery. The common targets in such operations are the postero
      ventral portion of the globus pallidus interna in the basal ganglia (for dopa
      induced dyskinesias particularly) and the ventro-intermediate nucleus of the
      thalamus (for tremor-predominant Parkinson's disease). Accurate and exquisite
      neurophysiological localisation of these small targets deep within the brain can
      be obtained with single-unit microelectrode technique prior to the insertion of a
      deep brain stimulator or definitive neurosurgical radiofrequency lesioning in the
      target area. This accuracy translates into better outcomes for patients and a
      reduced incidence of complications. The wealth of data gained from studying the
      abnormal behaviour of neurons within the basal ganglia and thalamus also provides
      us with fundamental insights into the pathophysiology behind Parkinson's disease.

PMID- 9285033
TI  - Williams syndrome--the Singapore General Hospital experience.
AB  - Williams syndrome first described in 1961 is generally characterised by mental
      deficiency, gregarious personality, unusual "elfin" facies, supravalvular aortic
      stenosis and idiopathic infantile hypercalcaemia. Patients with Williams syndrome
      show a hemizygous submicroscopic deletion of 7q11.23 detectable by fluorescent in
      situ hybridisation (FISH). The deleted portion of the chromosome corresponds to
      the Elastin gene. We report 3 girls with characteristics of Williams syndrome in
      whom the diagnosis was confirmed by demonstration of the hemizygous deletion of
      7q11.23 in the karyotype by FISH. These patients, aged 6, 7 and 10 years, showed
      the characteristic facies and gregarious personalities. Some developmental delay
      with mild mental deficiency and dysmorphic facies were prominent features in the
      initial presentation. Cardiac lesions found in these patients were small patent
      ductus arteriosus which closed, pulmonary valvular stenosis and mitral valve
      prolapse associated with mitral regurgitation respectively. Hypercalcaemia was
      not documented in these patients. Learning difficulty was a major issue and all
      patients required special schooling. Chromosome analyses done on peripheral blood
      were found to be normal in all patients. FISH using the Elastin Williams Syndrome
      Chromosome Region (WSCR) probes (oncor) showed the hemizygous deletion of
      7q11.23. Diagnosis of Williams syndrome can now be confidently confirmed with the
      help of FISH.

PMID- 9285032
TI  - Three cases of fatal pulmonary embolism in obstetrics.
AB  - We conducted a retrospective analysis of maternal deaths in our hospital from
      January 1992 to December 1995. Cases of fatal pulmonary embolism were identified
      and analysed with respect to their past history, antenatal and peripartum
      progress, clinical presentation and investigation. There were 7 maternal deaths
      during this period and autopsies were performed in all cases. Pulmonary embolism
      was the leading cause of maternal mortality, responsible for 3 deaths. The
      incidence of fatal pulmonary embolism was 4.9 per 100,000 maternities. One case
      occurred antepartum and 2 occurred postpartum. The antepartum case occurred after
      a period of immobilisation, and both postpartum cases occurred after emergency
      Caesarean sections. Dyspnoea and sudden cardiovascular collapse were the
      commonest presentations. Electrocardiograph and arterial blood gases were
      abnormal in both patients in whom the tests were performed. Death occurred within
      11 hours of presentation of symptoms in all 3 cases. Pulmonary embolism was more
      common among our population than previously reported, and was the leading cause
      of maternal mortality in our institution over the last 4 years. Immobilisation
      and Caesarean section were the major risk factors. Identification of high risk
      situation, antithrombotic prophylaxis and a high degree of suspicion were the key
      to reducing the incidence of fatal pulmonary embolism in obstetric patients.

PMID- 9285034
TI  - An evaluation of minimal residual disease in childhood acute lymphoblastic
      leukaemia.
AB  - Evaluation of minimal residual disease (MRD) in acute lymphoblastic leukaemia
      (ALL) is important for disease prognostication and early relapse detection. In
      this study, the rearranged third complementarity-determining-region (CDR-III) of
      immunoglobulin heavy chain (IgH) was used as a surrogate tumour marker for MRD
      evaluation. DNA obtained from marrows at diagnosis was amplified by the
      polymerase chain reaction (PCR) using a pair of consensus primers. After 2 rounds
      of DNA amplification and polyacrylamide gel separation, the nucleotide sequences
      of 87.5% (21/24) consecutive children with B-lineage ALL were obtained by
      automated sequencing. There were between 1-4 rearrangements per patient. Although
      the J5 and J6 joining regions were preferentially used, the rearranged sequences
      were unique for all 25 sequences obtained. Oligoprobes to the DNJ region were
      constructed and quantitation in 7 patients showed a detection sensitivity of 1
      leukaemic cell in 10(4) to 10(5) normal cells compared to 3 in 100 using
      conventional morphological criteria. Serial bone marrow showed progressive
      decrease in the quantity of leukaemic cells, and no leukaemic sequences were
      detected during cessation of therapy in 4/7 patients. One patient with detectable
      MRD, absconded treatment and eventually relapsed. These results are consistent
      with the need to eliminate the leukaemic clones below MRD detection levels before
      the end of therapy at 2 years. In conclusion, this study describes a novel,
      simplified and sensitive method of MRD detection in childhood leukaemia.

PMID- 9285035
TI  - The 1996 Runme Shaw Memorial Lecture: malaria--past, present and future.
AB  - Falciparum malaria may have infected Homo sapiens (and perhaps H erectus) in the
      Asia Pacific region for more than 100,000 years. This estimate is based on the
      gene frequency of alpha-thalassaemia, the protection it affords against
      falciparum malaria and assumptions of untreated mortality from the infection. Up
      until the end of the 19th century, there was a high mortality from malaria in the
      coastal parts of Malaya, but the malaria control campaign, begun in 1901 at
      Klang, was described by Sir Ronald Ross as the first successful antimalarial work
      in the (then) British Empire. This was extended to Singapore in 1911. When the
      Far Eastern Association of Tropical Medicine held its Fifth Biennial Congress in
      Singapore in 1923, malaria was still a major killing disease in parts of Malaya
      and Sarawak. The mechanism of life-threatening malaria involves cytoadherence of
      parasitised erythrocytes in microvascular beds, a process enhanced by the
      products of macrophage activation induced by malarial pyrogen. Improvements in
      the chemotherapy of life-threatening falciparum malaria with chloroquine and
      quinine have been countered by the emergence of resistant strains. Artemisinin
      derivatives may become the treatment of choice during the coming decade. Apart
      from traditional anti-mosquito methods, control of malaria now involves the use
      of insecticide-impregnated bed nets, new entomological strategies, including
      genetic manipulation of mosquitoes and selective chemoprophylaxis. Antigenic
      diversity and antigenic variation of the malaria parasite have so far defeated
      attempts to produce an effective vaccine.

PMID- 9285036
TI  - The inhalation acute toxic class method: test procedures and biometric
      evaluations.
AB  - A method of inhalation acute toxic (ATC) classification is presented with the use
      of significantly fewer animals in comparison with the classical LC50 test. The
      principle of the inhalation ATC method is based on the oral ATC method, which has
      been adopted in 1996 as an official test guideline of the OECD and the European
      Union. The inhalation ATC method, like the oral ATC method, is a stepwise
      procedure; three animals of each sex are used simultaneously for each tested
      concentration, and not, as in the oral ATC method, three animals of each sex
      separately for each dose. The method was developed for three starting
      concentrations and two reference systems (based on ppm and mg/l). Depending on
      the LC50, slope, classification system and starting concentration, on average 50
      to 80% fewer animals will be used in comparison to at least 30 animals with the
      classical LC50 test. The method was biometrically evaluated with the use of the
      probit model for dose-response relationships. At present, there are 12 different
      international classification systems based on LC50 values: 6 systems referring to
      mg/litre and 6 systems based on ppm values, and exposure time varying from 1 to 4
      h. The test procedures and the calculations of the classification probabilities
      demonstrate that the inhalation ATC method is a reliable alternative to the
      classical LC50 test with the use of significantly fewer animals. Classification
      probabilities are presented for all classification systems currently in use, and
      expected numbers of experimental and of moribund/dead animals are demonstrated
      for one system of each reference system and for all three starting
      concentrations. The conclusion is justified that there is no need to validate the
      inhalation ATC method with the use of experimental animals.

PMID- 9285037
TI  - Hepatotoxicity of diisopropyl ester of malonic acid and chloromalonic acids,
      disinfection by-products of the fungicide isoprothiolane.
AB  - The fungicide isoprothiolane (diisopropyl 1,3-dithiolane-2-ylidenemalonate)
      decomposes to the diisopropyl esters of malonic acid (DM), chloromalonic acid
      (DCM) and dichloromalonic acid (DDCM) upon aqueous chlorination. In this study,
      the cytotoxicity of these compounds was examined using rat hepatocytes cultured
      on Matrigel. DCM and DDCM caused hepatocellular death at concentrations > 0.5 mM,
      while DM had no effect on the cell viability even at the maximum concentration
      examined (4 mM). Significant lipid peroxidation, measured as 2-thiobarbituric
      acid reactive substances, was observed in both DCM- and DDCM-treated hepatocyte
      cultures, and was significantly enhanced by pretreatment with 0.1 mM bis(p
      nitrophenyl)phosphate (BNPP), a carboxylesterase inhibitor. When both BNPP and
      SKF-525A, a cytochrome P450 inhibitor, were present in the medium, DCM-induced
      cytotoxicity and lipid peroxidation were significantly suppressed compared to
      cultures with BNPP-treatment alone. By contrast, the DDCM-induced cytotoxicity
      was not affected by the combined pretreatment of SKF-525A and BNPP. These results
      indicate that DCM is metabolically activated by cytochrome P450 in an ester form,
      while DDCM is activated by a mechanism other than one involving cytochrome P450.
      To further elucidate the cytochrome P450 isozyme involved in the metabolic
      activation of DCM, microsomal lipid peroxidation was studied in vitro using
      microsomes from rats treated with beta-naphthoflavone, musk xylene,
      phenobarbital, pyrazole, or dexamethasone. Among these preparations, the
      microsomes from dexamethasone-treated rats showed the most extensive lipid
      peroxidation in the presence of DCM, and the lipid peroxidation was enhanced by
      BNPP as observed in hepatocyte cultures. These findings suggest the possible
      involvement of cytochrome P450 3A in the metabolic activation of DCM.

PMID- 9285039
TI  - Impaired cellular immune response in rats exposed perinatally to Baltic Sea
      herring oil or 2,3,7,8-TCDD.
AB  - While the immunotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been
      well established, the effects of complex environmental mixtures of
      polyhalogenated aromatic hydrocarbons (PHAHs) are poorly understood. Many PHAHs,
      including the polychlorinated-biphenyls (PCBs), -dibenzofurans (PCDFs), and
      dibenzo-p-dioxins (PCDDs), possess 'dioxin-like' activities, and accumulate in
      the aquatic food chain. Organisms occupying high trophic levels may therefore be
      exposed to concentrations which may present an immunotoxic risk. In this study,
      pregnant PVG rats were administered a daily oral dose of 1 ml of the following
      during pregnancy and lactation: (1) oil extracted from herring caught in the
      relatively uncontaminated Atlantic Ocean; (2) oil extracted from herring caught
      in the contaminated Blastic Sea; or (3) the Atlantic herring oil extract spiked
      with 2,3,7,8-TCDD. The daily intakes of aryl hydrocarbon (Ah)-receptor dependent
      toxic equivalents (TEQ) for mothers were 0.3 in the Atlantic group, 2.1 in the
      Baltic group, and 134 ng/kg body wt. in the 2,3,7,8-TCDD positive control group.
      Immune function and host resistance to rat cytomegalovirus (RCMV) were assessed
      in offspring aged 11, 25, 46 or 59 days. Rat pups in the positive control TCDD
      spiked group exhibited immunosuppression characterized by reduced thymus weight
      and cellularity, reduced thymocyte and splenocyte proliferative responses to T
      dependent mitogens in vitro, reduced virus-associated natural killer (NK) cell
      and specific antibody responses. While less pronounced, a similar pattern of
      effects was observed in the rat pups exposed only to the Baltic Sea herring oil.
      These immunotoxic effects were transient in both exposure groups, with a time
      related recovery in immune function possibly due to the half-life of TCDD in rats
      and the waning exposure levels in the rapidly growing pups. We previously
      demonstrated that the same Baltic Sea herring led to impaired natural killer cell
      and T-lymphocyte function in harbour seals during the course of a long-term
      captive feeding study. The collective results of these studies in rats and seals
      indicate the immunotoxic potential of environmental mixtures at current levels in
      the aquatic environment, and suggest that the developing immune system of young
      mammals may be at particular risk.

PMID- 9285038
TI  - Toxic effect of concomitant administration of cyclosporin A and acyclovir on
      renal function and morphology in rats.
AB  - The immunosuppressive agent cyclosporin A (CyA) and the antiviral drug acyclovir
      may cause renal functional impairment. CyA-induced immunosuppression increases
      the rate of viral infections. Therefore we were interested to determine whether
      short-term co-administration of CyA and acyclovir involves an increased
      nephrotoxic risk. Male Wistar rats were treated with CyA (20 mg/kg body wt.,
      s.c., once daily for 8 days), acyclovir (15 mg/kg body wt., s.c., 3-times daily
      for the last 5 days) or a combination of CyA and acyclovir. Blood levels of CyA
      were determined after a single dose. Urine was monitored for volume, osmolality,
      total protein and N-acetyl-beta-D-glucosaminidase (beta-NAG). Concentrations of
      blood urea nitrogen (BUN) and plasma-creatinine were determined (day 9). Renal
      cortical slices were monitored for accumulation of weak organic acids (para
      aminohippurate, PAH) and bases (tetra-ethylammonium, TEA) and for malondialdehyde
      (MDA) content. Renal histology was also examined. CyA induced a decrease in body
      and kidney weight, in urine osmolality and in the excretion of total protein.
      Plasma-creatinine and BUN as well as MDA content of renal tissues were increased
      by CyA. Acyclovir alone did not induce significant changes. In comparison to CyA
      values, urine volume and beta-NAG excretion were enhanced and TEA accumulation
      depressed by the concomitant administration of CyA and acyclovir. CyA- or
      acyclovir-treatment alone did not result in significant morphological changes. In
      the group co-administered CyA/acyclovir, the kidneys showed mild to moderate
      signs of tubulopathy. Short-term co-administration of CyA and acyclovir was
      concluded to have possibly increased nephrotoxic potential.

PMID- 9285040
TI  - Inhibition instead of enhancement of lipid peroxidation by pretreatment with the
      carcinogenic peroxisome proliferator nafenopin in rat liver exposed to a high
      single dose of corn oil.
AB  - Oxidative stress is discussed as a possible hepatocarcinogenic mechanism of
      peroxisome proliferators (PP) in rodents and is suggested to result from the
      induction of peroxisomal beta-oxidation (PBOX) by PP. The induced PBOX is assumed
      to produce excessive H2O2 from the degradation of fatty acids, ultimately leading
      to oxidative stress and lipid peroxidation. In the present short term-study, we
      attempted to stimulate lipid peroxidation in male Wistar rats by (1) inducing
      PBOX enzymes with the peroxisome proliferator nafenopin at 90 mg/kg body weight
      per day in the diet for 10-11 days, and (2) by supplying the induced PBOX with an
      abundant amount of fatty acid as substrate, using a corn oil gavage at 20 ml/kg
      body weight. The corn-oil gavage alone, i.e. without preceding nafenopin
      treatment, enhanced liver triacylglycerol nine- to tenfold and hepatic lipid
      peroxidation, measured as thiobarbituric acid reactive substances (TBARS), was
      increased 50% compared with controls. Both observations were made after 18 h when
      the peak elevations occurred. Upon pretreatment with nafenopin, associated with a
      sevenfold induction of PBOX, the corn oil gavage however caused only a threefold
      maximal increase in hepatic triacylglycerol, also at the 18 h time-point; TBARS
      remained almost at control levels, as monitored at seven time points over 24-25
      h. These results suggest that nafenopin reduces rather than enhances lipid
      peroxidation, despite the provision, in a short term study, of high doses of
      substrate to the induced enzyme system that is hypothetically causing oxidative
      stress in the liver.

PMID- 9285042
TI  - Styrene oxide DNA adducts: in vitro reaction and sensitive detection of modified
      oligonucleotides using capillary zone electrophoresis interfaced to electrospray
      mass spectrometry.
AB  - Styrene is one of the most important synthetic chemicals in the world and is
      subject to investigations concerning carcinogenicity and mutagenicity due to the
      active metabolite, styrene-7,8-oxide. This epoxide shows a tendency to react,
      among others, with DNA and DNA constituents. The in vitro reaction of styrene
      oxide with DNA was investigated by cleaving incubated calf thymus DNA with two
      different enzymes, namely Benzonase and alkaline phosphatase, to obtain
      oligonucleotides of the type n-nucleotide-(n-1)-phosphate with chain length from
      2 to 8 bases. Alkylated and nonalkylated nucleotides were separated in groups
      according to their chain length using capillary zone electrophoresis and were
      detected with electrospray mass spectrometry. This improvement in sensitivity
      made it possible to obtain new information about the reaction of styrene oxide
      with DNA, especially to detect unknown reaction products. The results indicate
      that primarily purine bases were alkylated by styrene oxide before pyrimidine
      bases, which react with higher concentrations of styrene oxide. This means that
      in addition to the already reported adducts in DNA at the N-7-, O6- and N2
      position of guanine also adducts at the nucleophilic sites of adenine can be
      found using mass spectrometry. We anticipate for the future this procedure will
      allow us to investigate base sequence specific reactions as well as interactions
      from xenobiotics and cytostatic drugs, since reaction products would directly be
      detectable.

PMID- 9285041
TI  - Relationship between acute toxicity of (bis)aziridinylbenzoquinones and cellular
      pyridine nucleotides.
AB  - The toxicity of aziridinylbenzoquinones may occur by a number of mechanisms,
      including oxidative stress caused by redox cycling and the activation of the
      aziridine groups. Isolated hepatocytes were used to assess the relationship
      between the redox status of NADP(H) associated with oxidative stress, the level
      of NAD(H) closely linked with DNA repair and the cytotoxicity of three 2,5
      bis(aziridinyl)-1,4-benzoquinones (BABQ). Exposure of hepatocytes to the BABQ
      TW13 (200 microM) and TW25 (100 microM), which are able to arylate and to redox
      cycle, resulted in increased intracellular NADP+ from < 0.3 nmol/mg protein to
      1.5 nmol/mg protein within 60 min. The increase in intracellular NADP+ was
      followed by the onset of cell death by 180 min. In contrast, exposure to lower
      concentrations of TW13 (100 microM), TW25 (50 microM) and carboquone (100-200
      microM) (which neither arylates nor redox cycles via a one-electron reduction)
      resulted in a less pronounced (< 1.0 nmol/mg) increase in NADP+ and there was no
      evidence of cell death within the 180 min incubation. BABQ had a concentration
      dependent effect on intracellular NAD+. Exposure of hepatocytes to TW13 (200
      microM) and TW25 (100 microM) resulted in a decrease in intracellular NAD+ from >
      2.7 to < 1.0 nmol/mg protein within 60 min. At concentrations of the BABQ where
      the level of NAD+ remained > 1.0 nmol/mg protein after 30 min, the hepatocytes
      remained viable at 180 min. These changes in intracellular pyridine nucleotides
      suggests two mechanisms may be involved in BABQ cytotoxicity. At high
      concentrations, aziridinylbenzoquines may cause cytotoxicity via oxidative stress
      following redox cycling. At lower concentrations however, the predominant
      pyridine nucleotide change is a prolonged depletion of NAD+, suggesting extensive
      DNA damage which may lead to delayed cell death.

PMID- 9285043
TI  - Influence of polymorphisms of GSTM1 and GSTT1 for risk of renal cell cancer in
      workers with long-term high occupational exposure to trichloroethene.
AB  - Suspected nephrocarcinogenic effects of trichloroethene (TRI) in humans are
      attributed to metabolites derived from the glutathione transferase (GST) pathway.
      The influence of polymorphisms of GSTM1 and GSTT1 isoenzymes on the risk of renal
      cell cancer in subjects having been exposed to high levels of TRI over many years
      was investigated. GSTM1 and GSTT1 genotypes were determined by internal standard
      controlled polymerase chain reaction. Fourty-five cases with histologically
      verified renal cell cancer and a history of long-term occupational exposure to
      high concentrations of TRI were studied. A reference group consisted of 48
      workers from the same geographical region with similar histories of occupational
      exposures to TRI but not suffering from any cancer. Among the 45 renal cell
      cancer patients, 27 carried at least one functional GSTM1 gene (GSTT1 +) and 18
      at least one functional GSTT1 gene (GSTT1 +). Among the 48 reference workers, 17
      were GSTM1 + and 31 were GSTT1 +. Odds ratio for renal cell cancer were 2.7 for
      GSTM1 + individuals (95% CI, 1.18-6.33; P < 0.02) and 4.2 for GSTT1 + individuals
      (95% CI, 1.16-14.91; P < 0.05), respectively. The data support the present
      concept of the nephrocarcinogenicity of TRI.

PMID- 9285044
TI  - A first evaluation of the natural high molecular weight polymeric Lumbricus
      terrestris hemoglobin as an oxygen carrier.
AB  - Lumbricus terrestris hemoglobin (LtHb), an unusually stable Hb (MW approximately
      4x10(6) Da) with respect to dissociation and oxidation, circulates
      extracellularly in the earthworm and at neutral pH exhibits oxygen affinity and
      cooperativity similar to that of human HbA. Results suggest that LtHb may serve
      as a model for a high molecular weight extracellular oxygen carrier. Mice and a
      rat model partially exchanged with LtHb showed no apparent behavioral and
      physical changes. 31P NMR spectroscopy of perfused guinea pig hearts, used to
      assess phosphocreatine levels as an indication of the ability of LtHb to serve as
      an oxygen carrier to the heart, demonstrated that LtHb provides oxygen to the
      tissue and maintains the energy metabolism significantly better than the control
      non-Hb perfusion media. One day after infusion, video enhanced microscopy imaging
      of the mice cremaster muscle vasculature reveals temporal adhesion of leukocytes
      to the endothelial walls with temporal infiltration of leukocytes to the
      surrounding tissue, correlated with dosage. Exchanged mice rechallenged with LtHb
      show no overt allergic response or death. Further evaluation of this natural
      extracellular Hb as a potential polymeric Hb blood substitute/perfusion agent is
      warranted.

PMID- 9285045
TI  - A new low density lipoprotein (LDL) adsorbent.
AB  - Crosslinked O-Carboxymethyl (O-CM) Chitosan beads were prepared by the reaction
      of O-CM Chitosan with glutaraldehyde solution. Results in vitro experiments with
      this new developed LDL adsorbent are presented. This adsorbent is capable of
      cutting down LDL-Cholesterol without significantly affecting HDL and TP (Total
      Proteins) levels in the plasma.

PMID- 9285046
TI  - Red cell granules: a new bio-absorbent for absorbing cyanide.
AB  - Granules of bovine and human red cells with a diameter about 4 mm and containing
      methemoglobin inside the cells were prepared artificially. These methemoglobin
      containing red cell granules were very effective for detecting and absorbing
      cyanide in water. Each one g of red cell granules (wet weight) absorbed about 4
      mg cyanide within an hour. An instant detector for cyanide was also devised by
      applying and gelling methemoglobin-containing red cells onto a filter paper. The
      granules may be useful for absorbing cyanide, which is used in large amounts in
      gilding factories and detoxified in water through complicated treatment systems.

PMID- 9285047
TI  - Structure and stability of human hemoglobin microparticles prepared with a double
      emulsion technique.
AB  - Hemoglobin solutions can be used as blood substitutes but they present some
      disadvantages often due to their rapid removal from the bloodstream after
      injection. A possible way of overcoming this problem is to trap hemoglobin inside
      particles. This study deals with the preparation, structure and stability of
      poly(lactic acid) and ethylcellulose microparticles containing human hemoglobin
      obtained with a double emulsion technique. We investigated the manufacturing
      process of these particles in order to increase the encapsulation ratio of
      hemoglobin. For this purpose, some parameters involved in the procedure were
      optimized, such as hemoglobin concentration and duration of stirring: hemoglobin
      loading increases with its concentration in the preparation and well-defined
      stirring time avoids a leakage of hemoglobin. Hemoglobin concentration,
      surfactant concentration i.e. poly(vinylic alcohol), amounts of polymer and
      solvent (methylene chloride), duration and speed of stirring. The microparticles
      were prepared with satisfactory yields (60 to 73%). They were spherical and their
      mean size was lower than 200 microns. The functional properties of entrapped
      hemoglobin were studied. The encapsulation did not alter hemoglobin and the
      oxygen affinity of the hemoglobin remained unmodified (P50 about 13.9 mm Hg in a
      Bis-Tris buffer pH 7.4 at 37 degrees C). Moreover, only low levels of
      methemoglobin could be detected (less than 3%). Besides, about 90% of
      encapsulated hemoglobin could be released from microparticles, with a speed
      related to the internal structure of the particles. The prepared microparticles
      were stored during one month at +4 degrees C. No degradation of the particle
      structure occurred and the functional properties of hemoglobin were preserved.
      These particles could provide a potential source of oxygen in the field of
      biotechnologies but any application for a transfusional purpose would first
      require a drastic reduction in particle size.

PMID- 9285048
TI  - Microdisperse form of immobilized hemoglobin modelling the erythrocytes.
AB  - Disperse systems based on hemoglobin sorption immobilization in reticular
      carboxylic polyelectrolytes are proposed as model of erythrocytes. The efficiency
      of oxygen transport of these systems is much higher than that of native
      hemoglobin and is comparable with the gas transport of erythrocytes. This is
      believed to be due to highly selective sorption of hemoglobin in microdisperse
      forms of permeable polyelectrolytes. Microparticles of immobilized hemoglobin
      exhibit high local concentration of hemoglobin: the protein mass being one order
      of magnitude than that of polymer-carrier. Besides, it is presumed that structure
      of the carboxylic polyelectrolyte matrix is a polymer analog of 2,3
      diphosphoglycerate. Microdispersion of immobilized hemoglobin exhibits a
      aggregative resistance and have identity of surface charge with erythrocytes.
      Studies in vivo have revealed biocompatibility of immobilized hemoglobin.

PMID- 9285049
TI  - Description of a project for the production and evaluation of oxygen-carrying
      hemosubstitutes.
AB  - Scarce availability and risk of transmission of infections and diseases (HIV,
      hepatitis B, Chagas' disease) limit the use and benefits of homologous blood
      transfusions for surgical purposes. Recent trials of perfluorocarbon-based
      hemosubstitutes (PFC-HSs) in experimental cardiopulmonary bypass (CPB) have
      demonstrated their ability to improve brain oxygenation, as compared with
      conventional crystalloid priming solutions. The objective of the project
      described here is to test different formulations of PFC-HSs and optimize their
      formulation and dosage for use in CPB. The project includes: (1) study the
      feasibility of implementing a laboratory for small scale production of PFC-HSs;
      (2) evaluate the efficacy of use of PFC-HSs in an animal model of CPB; and (3)
      evaluate the safety of use of PFC-HSs in an animal model of hemorrhagic shock.
      Several in-house PFC-HSs and outside PFC-HSs are being evaluated. The current
      state of the project is: (1) the feasibility study has been completed and several
      PFCs, emulsifiers and surfactants are being tested; (2) and (3) the animal models
      have been implemented are being used to test in-house and outside PFC-HSs as
      priming solutions in CPB and reinfusion fluids in hemorrhagic shock respectively.
      Some preliminary results are presented.

PMID- 9285050
TI  - Beneficial effects of oxygenated fluorocarbon on the in vitro culture of
      protoplasts and cell electrofusion products.
AB  - Electrofused Passiflora protoplasts (P. edulis, P. giberti) were plated in KPR
      medium overlaying oxygen-gassed perfluorodecalin (Flutec PP6). Oxygenated PFC
      significantly (P < 0.05) enhanced protoplast division, as reflected by an
      increase in mean plating efficiency of up to 62% (P < 0.05) over 14 days. After
      21 days of culture, the liquid phase containing dividing protoplast-derived
      cells, was removed from the PFC surface and overlaid onto MS-based agar medium
      for callus proliferation. Forty days later, protoplast-derived calli were
      transferred to one of two regeneration protocols, previously determined using
      unfused parental protoplasts. Calli derived from electrofusion-treated
      protoplasts exhibited organogenesis or somatic embryogenesis, depending on the
      regeneration procedure. The regeneration efficiency after 121 days for
      protoplasts initially cultured with oxygenated PFC was over 2-fold greater (P <
      0.01) than control. These results indicate that oxygenated PFC can enhance growth
      and regeneration of protoplasts and their fusion products.

PMID- 9285051
TI  - Progress toward preparation of universal donor red cells.
AB  - Coupling of an inert polymer to the surface of red cells was examined as a
      potential means of covering blood group antigens and producing cells that could
      serve as universal donor cells for transfusion. Effective blockade of red cell
      antigens was achieved with N-hydroxysuccinimide-activated esters of polyethylene
      glycol. It was possible to block all antigens tested, but lower concentrations of
      reactants were required to block peptide-defined antigens than carbohydrate
      defined antigens. Red cells remained intact after modification but were
      significantly damaged. Our results demonstrate the feasibility of antigenic
      blockade of red cells, but there is a need to reduce damage during coupling
      reactions to produce viable red cells.

PMID- 9285052
TI  - Effects of the co-polymer surfactant, Pluronic F-68, on platelet aggregation in
      human whole blood.
AB  - The effects have been studied of Pluronic F-68 on platelet aggregation in human
      whole blood. The median spontaneous platelet aggregation in normal blood (n = 15)
      was 18.4% [interquartile range (IQ) = 10.5-24.2%]. Commercial grade Pluronic F-68
      significantly (P < 0.05) reduced platelet aggregation at 7.3 microM (median =
      8.4%, IQ = 3.9-13.4; n = 12) and almost eliminated aggregation at concentrations
      of > 58 microM (median = 2.0%, IQ = 0.0-3.5). Similar results were obtained with
      a silica gelpurified Pluronic F-68 fraction (n = 3). Pluronic F-68 also
      accelerated the rate of platelet dis-aggregation in blood treated with 0.3, 1.0
      or 3.0 mM adenosine di-phosphate. These results suggest that the therapeutic
      effects of Pluronic F-68 in ischaemic injury may be due, in part, to inhibition
      of platelet aggregation in the microcirculation. The beneficial effects of tissue
      perfusion with oxygen-carrying perfluorochemical emulsions, containing Pluronic F
      68, may also involve direct effects of the surfactant on platelets.

PMID- 9285053
TI  - Isolation of intact transition protein 2 with three zinc finger motifs from boar
      late spermatid nuclei.
AB  - Boar intact transition protein 2, TP2, was isolated from the late spermatid
      nuclei by chromatography on Fractogel EMD SO3- 650 (M), and HPLCs on Nucleosil
      300 7C18, Diol-120 and Chemcosorb 3C18H. CD spectroscopy study showed that TP2
      underwent a small but significant zinc dependent secondary structural change.
      TP2, having three potential zinc finger motifs, was shown to be contain 3 atoms
      of zinc bound per molecule of the protein by atomic absorption spectroscopy.
      These results together with the amino acid sequence of TP2 suggest that TP2 is a
      zinc metalloprotein with three zinc finger structures.

PMID- 9285054
TI  - Fusion of phospholipid vesicles induced by the ribosome inactivating protein
      saporin.
AB  - The single chain ribosome-inactivating protein Saporin-S6 (SO-6) induces the
      fusion of acid phospholipid vesicles. The extent of fusion was measured by
      resonance energy transfer assay between the N-(7-nitro-2-1,3-benzoxadiazol-4-yl)
      dimyristoylphosphatidyl lithanolamine (NBD-PE)(donor) and N-(lissamine rhodamine
      B sulphonyl)-diacylphoshaidylethanolamine (Rh-PE) (acceptor) incorporated in the
      vesicle. The saturated lipid/protein molar ratio is approx. 100:1. The time
      course of fusion of vesicles induced by the protein showed that the process was
      completed within 10 minutes, and the size of the particles in the medium was
      enlarged which conforms the occurrence of the fusion occurring. The fusion is
      temperature dependent and the liquid-crystalline state lipid is more apt to fuse
      than the gel phase lipid. The effect of SO-6 is also dependent on ionic strength
      and pH, high salt concentration and basic pH may abolish fusion, which suggests
      that both electrostatic and hydrophobic components may be involved in the
      process.

PMID- 9285055
TI  - Isoform-specific monoclonal antibodies against HSP90.
AB  - The purpose of this study was to develop monoclonal antibodies (mAbs) that
      distinguish between the two isoforms of human 90-kDa heat shock protein (HSP90),
      i.e., HSP90 alpha and beta. Human HSP90 alpha and beta isoforms expressed in
      Escherichia coli were separately used as antigens for developing the mAbs. Twenty
      three and ten mAbs were obtained by immunization of mice with HSP90 alpha and
      beta, respectively. Among them, ten and three mAbs specifically recognized HSP90
      alpha and beta isoforms, respectively, on the criteria of both enzyme-linked
      immunosorbent and immunoblotting analyses. Immunochemical analysis by use of the
      mAbs revealed that both of the HSP90 isoforms were present in human cells even
      under unstressed conditions and that the expression of HSP90 alpha was more
      strongly induced when the cells were exposed to arsenate. This is the first
      report of the development of the mAbs discriminating between the two isoforms of
      HSP90. The mAbs specific for HSP90 isoforms should be useful for the regulational
      and functional analyses of HSP90 isoforms.

PMID- 9285057
TI  - Involvement of an endogenous metalloprotease in the activation of protoxin in
      Bacillus thuringiensis subsp. kurstaki.
AB  - Insecticidal crystal proteins harvested from sporulated cultures of Bacillus
      thuringiensis subsp. kurstaki contain the protoxin (Mr 132 kDa) and minor amounts
      of toxin (66 kDa). The proteolytic processing of 132 kDa protoxin to an active 66
      kDa toxin is brought about by exogenous proteases or larval gut enzymes. Under
      denaturing/reducing conditions this conversion is also mediated by endogenous
      protease(s) of the producer organism. This endogenous protease is identified as a
      metalloprotease as the activation process is inhibited by ethylenediamine
      tetraacetic acid at 2 mM concentration.

PMID- 9285056
TI  - NMR characterization of physicochemical properties of rat D-dopachrome
      tautomerase.
AB  - D-dopachrome tautomerase (DOPD) catalyzes the conversion of D-dopachrome to 5,6
      dihydroxyindole. DOPD was found to have amino acid sequence homology with
      macrophage migration inhibitor factor (MIF), suggesting that DOPD functions as a
      proinflammatory cytokine. We here demonstrate the physicochemical properties of
      DOPD by nuclear magnetic resonance (NMR). The native molecular weight of rat DOPD
      was about 37 kDa as calculated from Sephadex G-100 column chromatography. Since
      the deduced molecular weight of its cDNA (117 amino acid residues) is 12.5 kDa,
      it is assumed that DOPD exists as a homotrimer in native form. Since several
      methyl proton resonances were observed in the high magnetic field region of the
      one-dimensional 1H-NMR spectrum, DOPD appeared to have a hydrophobic core in
      which methyl groups and aromatic groups are located close to each other. From a
      simple integration of one-dimensional 1H-NMR spectra, the contents of the alpha
      helix, beta-strand, and random coil were calculated to be 16%, 68%, and 16%,
      respectively. Since the denaturation temperature of DOPD is exceedingly high at
      the range between 90-100 degrees C, it is considered that the high beta-strand
      content may contribute to its heat stability.

PMID- 9285058
TI  - A recombinant human fibronectin fragment facilitates retroviral mediated gene
      transfer into human hematopoietic progenitor cells.
AB  - Gene transfer into hematopoietic progenitor cells is increased when these cells
      are adherent to the carboxy-terminal chymotryptic fragment of human plasma
      fibronectin (FN30/35) containing the heparin binding domain (HBD) and the
      alternatively spliced type three connecting segment (IIICS) region. We report
      herein the production of a recombinant human fibronectin fragment comprised of
      the HBD and IIICS regions expressed by Sf9 insect cells following recombinant
      baculovirus infection. The resulting isolated peptide, HuBacFN, facilitated gene
      transfer into human hematopoietic cell lines and primary human hematopoietic
      progenitors to a level achieved with the purified human plasma FN30/35 peptide.

PMID- 9285059
TI  - Characterization of Ca2+ transport activity associated with a non-mitochondrial
      calcium pool in the rodent malaria parasite P. chabaudi.
AB  - Non-mitochondrial calcium deposits were investigated in the intraerythrocytic
      malaria parasite Plasmodium chabaudi at the trophozoite stage by means of
      arsenazo III in the presence of ATP and the mitochondrial poisons, antimycin and
      oligomycin. Addition of vanadate and 2,5-di-(t-butyl)-1,4-hydroquinone (BHQ),
      both known to interact with SERCA pump, induced calcium release by permeabilized
      parasites when the medium free calcium concentration was kept at 3.5 microM. The
      tumor promoter thapsigargin also caused elevation of the free calcium
      concentration in permeabilized parasites. Our results support the view that P.
      chabaudi sequesters calcium in an exchangeable form and maintains its calcium
      homeostasis by way of an endoplasmic reticulum Ca2+ pump.

PMID- 9285060
TI  - Cloning and characterization of a new silver-stainable protein SSP29, a member of
      the LRR family.
AB  - Silver-stainable proteins (SSPs) are aspartic acid-rich nuclear proteins which
      are silver stained under very specific conditions. Using a degenerate
      oligodeoxyncleotide probe which codes for acidic amino acid residues, a cDNA for
      a new SSP, referred to as SSP29, has been isolated. The cDNA-derived amino acid
      sequence shows SSP29 has a molecular mass of 29 kDa, leucine-rich repeats (LRR)
      near the NH2-terminal region and acidic clusters at the COOH-terminal portion,
      indicating that SSP29 is also a member of the LRR subfamily of acidic proteins
      which have been shown to be involved in antigen-mediated cellular responses,
      leukemogenesis and differentiation. SSP29 can be stained by Ag-NOR staining.
      SSP29 is expressed in all human tissues and cell lines tested, localized to
      nucleoplasm and translocated partially to the nucleoli after heat shock. Its
      interaction with RNA polymerase I suggests that SSP29 may participate in signal
      transduction that directs nucleolar activities by regulating ribosomal RNA
      biosynthesis.

PMID- 9285061
TI  - Free radicals in the cerebrospinal fluid are associated with neurological
      disorders including mitochondrial encephalomyopathy.
AB  - The free radical levels in the cerebrospinal fluid of 8 patients with
      neurological diseases and 9 undergoing lumbar anesthesia for surgery were
      measured. The ascorbate free radical level 10 min after lumbar puncture showed a
      positive correlation with the hydroxyl radical level. In the patient with
      mitochondrial encephalomyopathy, the levels of hydroxyl and ascorbate free
      radicals increased upon discontinuation of treatment and decreased upon its
      resumption, and the ascorbate free radical levels without therapy fell after
      lumbar puncture. The free radical levels in the cerebrospinal fluid may reflect
      the degree of oxidative stress in the central nervous system.

PMID- 9285062
TI  - The transcriptional repression of the human Cu/Zn superoxide dismutase(sod1) gene
      by the anticancer drug, mitomycin C(MMC).
AB  - The Cu/Zn superoxide dismutase(sod1) is one of the key enzymes that protects
      cells against oxidative stress. In order to investigate the effects of mitomycin
      C(MMC) on the induction of apoptotic cell death and on the sod1 transcription
      level, the CATs activity of HepG2 cells transfected with sod1 promoter
      CAT(chloramphenicol acetyl transferase) fusion reporter was measured after MMC
      treatment. The CAT assay showed that exposure of HepG2 cells to MMC decreased the
      transcription level of the sod1 gene. The accumulation of p53 tumor suppressor
      protein by MMC treatment of HepG2 cells was noted. In order to investigate the
      p53-negative response element in its promoter region, a p53 cotransfection
      experiment with serially deleted sod1 promoter/CAT reporter constructs was
      performed. The results show a significant reduction of CAT activity in all
      deletion reporter constructs. The results show that MMC treatment inhibited sod1
      gene transcription through p53-mediated transcriptional repression.

PMID- 9285063
TI  - Effect of selenium on human phospholipid hydroperoxide glutathione peroxidase
      expression and host cell susceptibility to lipid hydroperoxide-mediated injury.
AB  - We recently isolated stable transfectants expressing human phospholipid
      hydroperoxide glutathione peroxidase (PHGPx) from the cells of guinea pig cell
      line 104C1 (Biochem. Biophys. Res. Commun. 219, 486-491, 1996). Among them, one
      transfectant, designated 104C1/O4C, expressed high glutathione peroxidase
      activity toward dilinoleoyl phosphatidylcholine hydroperoxide (PCOOH); and
      another one, 104C1/O2D, moderate activity. In the present study, we investigated
      the effect of selenium on the PHGPx activity and on the lipid hydroperoxide
      mediated cell injury in the transfectants to clarify further the action of PHGPx
      in preventing oxidative injury of the cells. When transfectant 104C1/O2D cells
      were cultured in the medium added with 250 nM selenium, glutathione peroxidase
      activity toward PCOOH increased 8-fold. Western blot analysis also revealed an
      increase in the amount of protein immunoreactive against anti-rat PHGPx antibody
      in this transfectant. Lipid hydroperoxide-mediated cell injury to the
      transfectant 104C1/O2D was significantly suppressed in accordance with the
      increase in the enzyme activity when the cells were cultured in the medium added
      with selenium. On the contrary, neither glutathione peroxidase activity toward
      PCOOH nor susceptibility to the injury was affected by selenium addition to the
      medium of the parental 104C1 cells, which have no selenium-dependent glutathione
      peroxidase. These results clearly support our previous conclusion that expression
      of PHGPx is responsible for the protection of host cells from lipid hydroperoxide
      mediated injury.

PMID- 9285064
TI  - Proteolytic activities of mouse sarcoma 180 cells that are inhibited by Bowman
      Birk and Kunitz protease inhibitors.
AB  - In this study, using zymogram analysis two proteolytic activities were identified
      in the mouse sarcoma 180 (S-180) cells that were activated by trypsin treatment
      and inhibited by both BBI and ACTI. These enzymes, with molecular weights of 46
      kDa (dominant band) and 62 kDa (minor band), were mainly localized in the
      cytosol, and had optimal activity at pH 7 and 8 respectively. Their inhibition by
      DFP, BBI and ACTI but not EDTA and TPCK indicated they were trypsin-like serine
      proteases and may be the intracellular target-enzymes of protease inhibitors. The
      level of the precursor of the 62 kDa protease was significantly increased in the
      S-180 solid and soft tumors, whereas the level of the 46 kDa precursor was almost
      undetectable, implying that a physiological role may be played by these serine
      proteases during tumor invasion.

PMID- 9285065
TI  - Nonenzymatic reduction of brucine N-oxide by the heme group of cytochrome P450.
AB  - Evidence showing that cytochrome P450-mediated reduction of brucine N-oxide to
      brucine by rat liver microsomes proceeds nonenzymatically in the presence of both
      a reduced pyridine nucleotide and FAD is presented. The microsomal N-oxide
      reduction appears to proceed in two steps: The first step is reduction of FAD by
      NADPH or NADH either enzymatically or nonenzymatically. The second step is
      nonenzymatic reduction of the tertiary amine N-oxide by the reduced flavin and is
      nonenzymatically catalyzed by the heme group of cytochrome P450.

PMID- 9285066
TI  - Activity profile of placental superoxide-superoxide dismutase system in pregnant
      mice and its possible relation with placental steroidogenesis.
AB  - Placenta in mouse generate increasing quantities of superoxide dismutase from day
      13 of pregnancy until parturition. This is associated with a concomitant
      reduction in the activity of superoxide radical. This findings points to the
      steroidogenic control of the later half of pregnancy by the placental axis.
      Parturition is associated with an abrupt spurt in superoxide radical. This is a
      novel finding and could be a consequence of the estrogen surge at labour. It is
      suggested that this abrupt increase in superoxide radical level at parturition
      may remould the placental membrane fluid at the point of its attachment with
      uterine membranes so as to facilitate the separation of placenta from uterus.

PMID- 9285067
TI  - Autolytic site mutant R105C of rat trypsin.
AB  - The autolytic site Arg105 of rat trypsin was replaced with Cys by DNA site
      directed mutagenesis method. Comparison of expression and purification of R105C
      trypsin along with the wild type and some other Arg105 mutants indicates that
      R105C trypsin could be expressed as well but with a lower expression level. It is
      unexpected that R105C trypsin has no detectable activity toward trypsin substrate
      TAME, quite different from the wild type and other Arg105 mutants. Native gel
      electrophoresis analysis indicates that R105C trypsin has a similar mobility rate
      to that of wild type trypsin. FPLC also gives similar retaining time. The loss of
      activity of R105C trypsin may result from the conformational change around active
      site, but not the dimer formation.

PMID- 9285068
TI  - Effects of vitamin E and selenium on antioxidant defense in rat heart.
AB  - Heart mitochondria, isolated from rats fed diets deficient or supplemented with
      vitamin E (E) and/or selenium (Se), were subjected to time-course assays of lipid
      peroxidation stimulated by ascorbate/ADP/Fe3+. Mitochondria depleted of alpha
      tocopherol (alpha-TH) peroxided rapidly as assessed by formation of
      thiobarbituric acid reactive substances (TBARS). Formation of TBARS was strongly
      inhibited in mitochondria from rats fed diets supplemented with E. Selenium
      deficiency, reduced glutathione (GSH), glutathione disulfide (GSSG) or GSH + GSSG
      did not affect the course of lipid peroxidation in mitochondria from rats
      supplemented or deficient in E. Combined E and Se deficiency resulted in
      significantly lower total (oxidized+reduced) mitochondrial coenzyme Q-9 (CoQ-9)
      concentration compared with control rats supplemented with dietary E and Se. Time
      course changes in mitochondrial alpha-TH and total CoQ-9 during oxidizing
      conditions were minor in +E rats. Total CoQ-9 was reduced substantially, however,
      during the course of lipid peroxidation in mitochondria depleted of alpha-TH.
      Selenium-dependent glutathione peroxidase (Se-GSHPx) activity was reduced by
      approximately 96% in heart cytosol, and to a somewhat lesser extent in
      mitochondria, by dietary Se deficiency. Non-Se GSHPx activity was not detected in
      heart cytosol but was detected in very small amounts in heart mitochondria.
      Glutathione S-transferase activity of heart cytosol was decreased in E and/or Se
      deficiency. The results of these experiments indicate that membrane alpha-TH was
      most effective in inhibiting lipid peroxidation in heart mitochondria.

PMID- 9285069
TI  - Mitochondrial ubiquinol-cytochrome c reductase and cytochrome c oxidase:
      chemotherapeutic targets in malarial parasites.
AB  - In order to demonstrate that the mitochondrial electron transport system may be a
      target for antimalarial drug design in the human malarial parasite Plasmodium
      falciparum, ubiquinol-cytochrome c reductase and cytochrome c oxidase were
      purified from mitochondria of the parasite cultivated in vitro. It was found that
      the catalytic efficiency of the two enzymes from the malarial parasite were
      markedly lower than those from mouse liver mitochondria. The classical inhibitors
      affecting different quinone binding sites of the mammalian reductase, antimycin
      and myxothiazole, which had little antimalarial activities on P.falciparum growth
      in vitro, were found to exhibit little inhibitory effect against the parasite
      reductase. The malarial parasite reductase was more sensitive to inhibition by
      the antimalarial drug, 2-[trans-4-(4'-chlorophenyl)cyclohexyl]-3-hydroxy-1,4
      naphthoquinone, than the mammalian enzyme, suggesting both the therapeutic
      potential of the target and the drug.

PMID- 9285070
TI  - Oxidized low-density-lipoprotein triggers programmed death of endothelial cells.
AB  - Incubation of bovine aortic as well as human umbilical vein endothelial cells
      with either oxidized or native low-density-lipoprotein in the presence of trace
      amounts of copper induced morphological changes of the cells and chromatin
      fragmentation characteristic for programmed cell death. Shrinkage of cells was
      evident after 6 to 8 hours of incubation and clearly preceded release of lactate
      dehydrogenase as a marker of cell permeability. Condensation of nuclear chromatin
      and internucleosomal cleavage was demonstrated by Hoechst staining and gel
      electrophoresis, respectively. Thus, by inducing active death of endothelial
      cells oxidized low-density-lipoprotein might negatively influence tissue
      homeostasis of the endothelium and thereby promote the development of
      atherosclerotic plaques.

PMID- 9285071
TI  - Evidence for antioxidant nutrients-induced pigmentation in skin: results of a
      clinical trial.
AB  - The aim of this study was to demonstrate that modification of the cellular redox
      equilibrium occurs as a consequence of antioxidant nutrients intake (carotenoids,
      vitamine E and vitamine C) and that these nutrients play a role in the
      pigmentation of the skin without any UV exposure. We conducted a randomized,
      double-blind study in 20 healthy subjects to evaluate and to compare the efficacy
      of two mixtures of dietary antioxidants with regard to direct determination of
      melanin and carotenes by chromametry at selected skin sites and multiple
      reflection spectrometry from a 1 cm2 region of skin of different parts of the
      body. Efficacy was assessed by a significant improvement of these parameters, in
      comparison with measurements performed on the day of randomization, before
      dietary supplement intake. The formulations per capsule of study dietary
      supplements are: 13 mg of beta-carotene, 2 mg of lycopene, 5 mg of vitamine E and
      30 mg of vitamine C (B13/L2) or 3 mg of beta-carotene, 3 mg of lycopene, 5 mg of
      vitamine E and 30 mg of vitamine C (B3/L3). A 8-week B13/L2-supplementation lead
      to a detectable carotenodermia whereas the B3/L3-supplementation not. Signicative
      increase of melanin concentrations in skin were found after 4, 5, 6 and 8 weeks
      of dietary antioxidant intake in both groups (p < 0.05). These results are
      discussed with regard to the redox control theory of melanocytes which regulates
      the tyrosinase activity.

PMID- 9285072
TI  - Purification and characterization of manganese superoxide dismutase from
      Ganoderma microsporum.
AB  - Manganese superoxide dismutase (Mn-SOD) in the mycelium of Ganoderma microsporum
      was purified to homogeneity by heat treatment at 70 degrees C, ammonium sulfate
      fractionation, DEAE-52 anion-exchange chromatography, and Sephacryl SH-200
      chromatography. The molecular mass of its native form was estimated to be 98 kD
      by size-exclusion chromatography. This enzyme is tetrameric composed of four
      subunits of equal size of 25 kD. The pI of this purified Mn-SOD was located at pH
      6.34 and 5.06 by isoelectric focusing. Comparisons of 17 amino acids from the N
      terminus of Mn-SOD subunit with the derived amino acid sequences from the
      reported Mn-SOD cDNA clones of other sources indicated a high degree of homology
      among the Ganoderma genus but the Mn-SOD from G. microsporum showed a high
      variation when compared with other organisms.

PMID- 9285073
TI  - Residues K128-Q175 of human interleukin-6 are essential for its biological
      activity.
AB  - Internal deletion K128-Q175 of the human interleukin-6 (hIL-6) has been generated
      at the cDNA level. With pBV220 as expressing vector, the recombinant pBV*-DIL-6
      encoding the deletion mutant (12 kD) of hIL-6 has been constructed. The resulted
      recombinant plasmids were then used to transform E. coli strain HB101, and the
      expression in the PLPR promoter system, which is temperature-regulatable, was
      achieved. After purification and renaturation, the biological activity of the
      expressed product, designated as DM120, was measured by MTT method in an IL-6
      dependent cell line 7TD1. The results show that the amino acid residues of IL-6
      128 to 175 are crucial for IL-6 activity. Receptor binding assay in vitro
      indicates that the entire region is not involved in forming the receptor binding
      surface.

PMID- 9285074
TI  - Purification and biochemical characterisation of human placental acid alpha
      glucosidase.
AB  - An acid alpha-glucosidase (EC 3.2.1.3) has been purified to electrophoretic
      homogeneity from the soluble fraction of the human term placenta. In the presence
      of SDS, two doublets of 79 and 67 kDa were seen in addition to other bands of
      extremely low intensity. Each of these bands was seen to cross-react with
      polyclonal antiserum raised to the purified enzyme, thus confirming the
      homogeneity of the preparation. The purified enzyme exhibited a broad substrate
      specificity. The kinetic data revealed the possible presence of multiple
      substrate binding sites. Chemical modification using group specific reagents
      indicated the presence of a carboxyl group and tryptophan at the active site.
      Based on these results a possible structure for the active site of the human term
      placental acid alpha-glucosidase has been proposed.

PMID- 9285075
TI  - Protection by histidine against oxidative inactivation of AMP deaminase in yeast.
AB  - Oxidative inactivation of AMP deaminase and its protection were analyzed under
      the in situ conditions of yeast cells. AMP deaminase was readily inactivated by
      an exposure to hydrogen peroxide plus copper in permeabilized yeast cells.
      Addition of ascorbic acid further enhanced the inactivation of the enzyme,
      suggesting the hydroxyl radical produced by the Fenton reaction is responsible
      for the inactivation of the enzyme. Addition of histidine caused an effective
      protection against the inactivation of AMP deaminase by hydrogen peroxide-induced
      hydroxyl radical. The concentration of histidine required for half-maximal effect
      was within physiological range. Cysteine showed less effective protection against
      oxidative inactivation. Other amino acids as potent copper-chelating agents as
      well as trolox and taurine showed little or no effect. Histidine can act as a
      physiological "antioxidant" in yeast cells.

PMID- 9285076
TI  - Occurrence of nonenzymatic N-acetylation of sphinganine with acetyl coenzyme A
      producing C2-H2-ceramide and its inconvertibility to apoptotic C2-ceramide.
AB  - Sphinganine, a biosynthetic precursor of ceramide, was non-enzymatically
      acetylated with acetyl coenzyme A at the C-2-amino residue to produce C2-H2
      ceramide (N-acetyl sphinganine) in an organic solvent and in an aqueous solution
      with a high yield, whereas sphingenine was only acetylated slightly. The
      structure of the N-acetyl sphinganine was identified with mass spectrum, and with
      chromatography using an authentic N-acetylated substance. Furthermore, the C2-H2
      ceramide was examined for enzymatic desaturation to determine whether C2
      ceramide, a cell-permeable ceramide responsible for apoptosis of cells, was
      produced, revealing an inferior substrate for H2-ceramide desaturase of horse
      brain microsomes.

PMID- 9285078
TI  - Relationship between prophylactic effect of lithium therapy and family history of
      affective disorders.
AB  - Lithium therapy response and age of onset (AOO) were studied in 98 patients with
      bipolar affective disorder (BPAD) who were divided into subgroups depending on
      type of family history of affective disorders. The highest (33.0 years) and
      lowest (25.5 years) age of onset were found in nonfamilial patients and in
      familial patients with a first-degree relative of BPAD, respectively. Nonfamilial
      patients showed the best response to lithium. There were 0.9 episodes/year off
      lithium compared to 0.3 episodes/year on lithium (an 88% decrease). A poorer
      response (a 71% decrease; a reduction from 1.39 episodes per year off lithium to
      0.65 on lithium) was found in familial patients with a first-degree relative of
      BPAD. Differences in serum lithium values between the groups could not explain
      the observed differences. Thus, familial patients showed a more severe
      manifestation of the disease with an earlier AOO and a lower prophylactic effect
      of lithium.

PMID- 9285077
TI  - A repeat proton magnetic resonance spectroscopy study in social phobia.
AB  - Peak spectral amplitudes for choline moieties (Cho), creatine (Cr), N
      acetylaspartate (NAA), and myo-inositol (mI) were examined using proton magnetic
      resonance spectroscopy in 19 social-phobia patients and 10 controls. Compared
      with controls, social phobics demonstrated significantly lower NAA/Cho and higher
      Cho/Cr, mI/Cr, and mI/NAA amplitudes in cortical gray matter. Higher mI/Cr and
      mI/NAA amplitudes for social phobics were also observed in subcortical gray
      matter. Minimal between-group differences were noted for white matter. Symptom
      severity correlated inversely with amplitudes primarily in subcortical gray
      matter, and to a lesser extent in cortical gray matter. Inclusion of age and sex
      in statistical modeling strengthened comparisons with controls but eliminated
      those for symptom severity. No changes were observed in any amplitude measure
      following at least 8 weeks of clonazepam treatment, nor was a relationship
      observed between amplitudes and cumulative clonazepam dose. The possible
      psychobiological implications of our findings in social phobia are discussed.

PMID- 9285080
TI  - The functional neuroanatomy of anxiety: a study of three disorders using positron
      emission tomography and symptom provocation.
AB  - Previous neuroimaging research has contributed insights regarding the neural
      substrates of specific psychiatric disorders. The purpose of this study was to
      determine the shared mediating neuroanatomy of anxiety symptoms across three
      different anxiety disorders. Data were pooled from 23 right-handed adult
      outpatients meeting criteria for obsessive-compulsive disorder, simple phobia, or
      posttraumatic stress disorder. Relative regional cerebral blood flow (rCBF) was
      measured using positron emission tomography in the context of symptom provocation
      paradigms. Symptom severity was measured via self-reports. The analysis of pooled
      imaging data indicated activation in right inferior frontal cortex, right
      posterior medial orbitofrontal cortex, bilateral insular cortex, bilateral
      lenticulate nuclei, and bilateral brain stem foci during the symptomatic versus
      control conditions. A positive correlation was found between rCBF at one brain
      stem locus and subjective anxiety scores (r = .744, p < .001). These findings
      suggest that elements of the paralimbic belt together with right inferior frontal
      cortex and subcortical nuclei mediate symptoms across different anxiety
      disorders. In addition, activation at one brain stem locus appears to be
      associated with the subjective severity of anxiety. Further studies are warranted
      to determine whether these same brain systems mediate normal anxiety states as
      well.

PMID- 9285079
TI  - Electrophysiological indices of information processing in methylphenidate
      responders.
AB  - Event-related potential (ERP) studies report that the positive deflection
      following stimulus evaluation at 300 msec (P3) in hyperactive children is
      augmented by methylphenidate (MP). This study investigates P3 and preceding ERP
      components using an auditory oddball task in attention-deficit hyperactivity
      disorder (ADHD). Mismatch negativity, negativity at 100 and 200 msec, and
      positivity at 200 msec and 300 msec (P3) were obtained from 14 control and
      hyperkinetic children. ADHD children who responded to MP were tested on two
      separate days while receiving either MP or placebo. Controls were tested once. No
      differences were found between groups for ERP components preceding P3. P3
      amplitude was significantly larger under MP than under placebo, but did not
      differ from controls. Under MP, differences in P3 amplitude unexpectedly occurred
      when no response was required. A P3 amplitude increase under MP and the
      unexpected P3 suggest that MP affects attention regulation.

PMID- 9285081
TI  - Darkness facilitates the acoustic startle reflex in humans.
AB  - The effects of darkness on startle reactivity and prepulse inhibition were
      investigated in two studies with 25 subjects participating in each study.
      Acoustic startle stimuli that were or were not preceded by an acoustic prepulse
      were delivered in alternating periods of complete darkness or light. In both
      studies, darkness significantly increased the magnitude of startle but did not
      affect prepulse inhibition (PPI). The PPI results suggest that darkness did not
      increase attention to the auditory modality, so that the startle facilitation in
      the dark probably did not result from an attentional process. The increased
      startle in the dark was significantly correlated with the intensity of subjects'
      fear of the dark as children based on retrospective rating scales. It is
      hypothesized that the startle facilitation in the dark results from a change in
      affect rather than from a change in attention.

PMID- 9285082
TI  - Anxiogenic effects of high illumination levels assessed with the acoustic startle
      response in rats.
AB  - Previous studies have shown that the amplitude of the acoustic startle reflex is
      increased by the presentation of aversive stimuli. In the present study, the
      amplitude of acoustic startle in rats was increased by exposure to high
      illumination levels. The effect was directly related to the intensity (0, 8, 70,
      and 700 footlamberts) of illumination (experiment I); was blocked by the
      anxiolytic compound buspirone (experiment II); and showed little or no
      habituation with repeated testing (experiment III). These results suggest that
      the elevation of startle amplitude by light may reflect an unconditioned
      anxiogenic effect of high illumination levels. The possible utility of this
      phenomenon as an animal model of anxiety is discussed.

PMID- 9285083
TI  - Event-related potential evidence for frontal cortex effects of chronic cocaine
      dependence.
AB  - We examined the effects of cocaine dependence and cocaine and alcohol
      codependence on the P3A event-related potential component. Ten chronic cocaine
      dependent subjects, 10 chronic cocaine and alcohol codependent subjects, and 20
      controls were studied in an auditory paradigm that included target, nontarget,
      and novel rare nontarget conditions. Substance-dependent subjects were abstinent
      from cocaine and/or alcohol for 2-6 weeks. Eighteen of these subjects (4 chronic
      cocaine-dependent subjects, 4 chronic cocaine/alcohol codependent subjects, and
      10 normal controls) were also studied in an analogous visual paradigm. In the
      auditory modality, the latency of the P3A response in the novel rare nontarget
      condition was delayed and its amplitude was reduced in both substance-dependent
      samples compared to controls. Comparable results were found for the smaller
      samples studied in the visual modality. These results suggest that chronic
      cocaine dependence produces deficits in frontal cortex functions.

PMID- 9285084
TI  - Lack of evidence for a major locus for bipolar disorder in the pericentromeric
      region of chromosome 18 in Irish pedigrees.
AB  - Seven families, multiply affected by bipolar mood disorder, have been collected
      from the Irish population and have been genotyped with microsatellite markers
      from the pericentromeric region of chromosome 18, a region that has been
      implicated as a site for a susceptibility gene for this relative common
      psychiatric disorder. The families significantly excluded linkage of bipolar
      disorder to this region under various models. Although the data provided no
      evidence of linkage heterogeneity among families, the number of families
      investigated may be too small to exclude completely the possibility of linkage in
      a small number of families.

PMID- 9285085
TI  - Brain abnormalities in murderers indicated by positron emission tomography.
AB  - Murderers pleading not guilty by reason of insanity (NGRI) are thought to have
      brain dysfunction, but there have been no previous studies reporting direct
      measures of both cortical and subcortical brain functioning in this specific
      group. Positron emission tomography brain imaging using a continuous performance
      challenge task was conducted on 41 murderers pleading not guilty by reason of
      insanity and 41 age- and sex-matched controls. Murderers were characterized by
      reduced glucose metabolism in the prefrontal cortex, superior parietal gyrus,
      left angular gyrus, and the corpus callosum, while abnormal asymmetries of
      activity (left hemisphere lower than right) were also found in the amygdala,
      thalamus, and medial temporal lobe. These preliminary findings provide initial
      indications of a network of abnormal cortical and subcortical brain processes
      that may predispose to violence in murderers pleading NGRI.

PMID- 9285086
TI  - Suppression of melatonin secretion by bright light in seasonal affective
      disorder.
AB  - Eleven patients with winter seasonal affective disorder and 10 healthy controls
      were exposed to light of 3300 lux for 5 min and for 1 hour respectively on
      consecutive evenings at 22:00 hours during winter and summer. In the winter, the
      measurements were undertaken both before and after the treatment with bright
      light for 2 weeks. In the summer, there was no treatment. Melatonin concentration
      in saliva and subjective sleepiness were measured at 22:00 and 23:00 hours on
      each test. There was no significant difference in the suppression of melatonin in
      response to the light tests between the patients and the controls. Exposure to
      light reduced the level of subjective sleepiness more among the patients compared
      to the control subjects. This reduction was not associated with the change in
      melatonin secretion nor the improvement in depressive symptoms.

PMID- 9285087
TI  - Increase in salsolinol level in the cerebrospinal fluid of parkinsonian patients
      is related to dementia: advantage of a new high-performance liquid chromatography
      methodology.
AB  - The study was carried out on the lumbar cerebrospinal fluid (CSF) samples taken
      from nonparkinsonian, early parkinsonian, and advanced parkinsonian patients.
      Some patients showed dementia, and some were treated with L-dopa. In the samples,
      salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) was assayed
      with a newly developed sensitive high-performance liquid chromatography (HPLC)
      method; 3-O-methyldopa (3-O-MD) and homovanillic acid (HVA) were also assayed by
      HPLC. CSF salsolinol concentrations were significantly enhanced in patients with
      signs of dementia, regardless of the degree of parkinsonism, and were not
      affected by L-dopa treatment; HVA and, particularly, 3-O-MD levels were elevated
      in patients receiving L-dopa. The strong association of CSF salsolinol level with
      dementia, but not with L-dopa treatment suggests that salsolinol does not
      originate from L-dopa metabolism, and that its elevation is an indicator of
      neurodegenerative processes resulting in damage to brain areas mediating
      cognitive functions. We found no correlation between the advancement of
      parkinsonism and the concentrations of 3-O-MD and HVA.

PMID- 9285088
TI  - Depression associated with pontine vascular malformation.

PMID- 9285089
TI  - Pimozide augmentation for the treatment of schizophrenic patients who are partial
      responders to clozapine.

PMID- 9285090
TI  - Mental disorders in diabetic patients with mitochondrial transfer RNA(Leu) (UUR)
      mutation at position 3243.

PMID- 9285091
TI  - Lewy body variant of Alzheimer's disease (AD) identified by postmortem ubiquitin
      staining in a previously reported case of AD associated with REM sleep behavior
      disorder.

PMID- 9285092
TI  - Biochemistry and function of hypusine formation on eukaryotic initiation factor
      5A.

PMID- 9285093
TI  - Growth of studies on hypusine in biological systems.

PMID- 9285094
TI  - Hypusine is essential for eukaryotic cell proliferation.
AB  - Hypusine [N epsilon-(4-amino-2-hydroxybutyl)lysine] occurs in all eukaryotes at
      one residue in a highly conserved protein, the putative eukaryotic translation
      initiation factor 5A (eIF-5A, old terminology eIF-4D). This unusual amino acid is
      produced in a unique posttranslational modification reaction that involves the
      conjugation of the 4-aminobutyl moiety of the polyamine spermidine to the epsilon
      amino group of a specific lysine residue of the eIF-5A precursor protein to form
      the deoxyhypusine [N epsilon-(4-aminobutyl)lysine] residue and its subsequent
      hydroxylation. The strict specificity of hypusine synthesis, its derivation from
      spermidine and its requirement for the activity of eIF-5A and for eukaryotic cell
      proliferation have raised keen interest in the physiological function of the
      hypusine-containing protein, eIF-5A.

PMID- 9285095
TI  - Eukaryotic initiation factor 5A activity and HIV-1 Rev function.
AB  - Eukaryotic initiation factor 5A (eIF-5A) is the only cellular protein known to
      contain the unusual amino acid hypusine, a modification that appears to be
      required for cell proliferation. This hypusine-modified protein stimulates
      synthesis of methionyl-puromycin in an in vitro assay which mimics the formation
      of the first peptide bond during protein synthesis, although the exact role of
      eIF-5A in vivo is still unknown. The unexpected finding that eIF-5A is a cellular
      cofactor of the HIV-1 Rev trans-activator protein may, however, provide a novel
      opportunity to reveal precisely what function eIF-5A performs in eukaryotic
      cells. In this review article, we first present a brief description of HIV-1 Rev
      function, followed by an overview of the data that identified eIF-5A as a Rev
      cofactor and, finally, discuss novel findings with respect to cellular eIF-5A
      activities.

PMID- 9285096
TI  - Two distinct pathways for intronless mRNA expression: one related, the other
      unrelated to human immunodeficiency virus Rev and human T cell leukemia virus
      type I Rex functions.
AB  - Intronless mRNAs were classified into two classes based on the sensitivities of
      their expression to the inhibitory effect of TAgRex, a dominant-negative mutant
      of the Rex protein of human T cell leukemia virus type I, and their abilities to
      express the genes encoded in the intron of the human immunodeficiency virus (HIV)
      genome. Interferon-alpha mRNA could not induce the expression of the env gene of
      HIV, and its expression was resistant to TAgRex. In contrast, the
      posttranscriptional regulatory element (PRE), necessary for the nucleo
      cytoplasmic export of mRNAs of hepatitis B virus, induced expression of the
      chloramphenicol acetyl transferase gene located within the intron of the HIV
      genome. PRE-mediated expression was inhibited by TAgRex. Thus, these results
      suggest that there are at least two distinct pathways for intronless mRNA
      expression, one related to and the other unrelated to Rev and Rex functions.

PMID- 9285097
TI  - Effects of inhibitors of RNA and protein synthesis on the subcellular
      distribution of the eukaryotic translation initiation factor, eIF-5A, and the HIV
      1 Rev protein.
AB  - The subcellular distributions of the endogenous eukaryotic translation initiation
      factor, eIF-5A, and Rev, a protein of the human immunodeficiency virus proposed
      to interact with eIF-5A, were studied in COS-7 cells treated with inhibitors of
      RNA or protein synthesis. We have previously shown that transiently expressed Rev
      is localized in the nucleolus, whereas eIF-5A is primarily in the cytoplasm. The
      subcellular localization of Rev was not affected by treatment with protein
      synthesis inhibitors (cycloheximide, CHX, 10 micrograms/ml; puromycin, 10
      micrograms/ml), although its location changed from predominantly the nucleolus to
      the cytoplasm after treatment with RNA synthesis inhibitors (actinomycin D, 4
      micrograms/ml, and 5,6-dichloro-1 beta-D-ribofuranosylbenzimidazole, DRB; 0.1
      mM), as previously reported. In contrast, none of the RNA synthesis inhibitors
      (alpha-amanitin, 10 micrograms/ml; actinomycin D, 4 micrograms/ml, and DRB, 0.1
      mM) caused any significant changes in the subcellular distribution pattern of eIF
      5A. However, treatment with puromycin, a protein synthesis inhibitor known to
      dissociate ribosomes, dramatically altered the subcellular distribution pattern
      of eIF-5A in 30% of the cell population. In these cells, the staining of eIF-5A
      was changed from an endoplasmic reticulum (ER) net work-like perinuclear
      structure to a patched dotted pattern dispersed throughout the cytoplasm. This
      change was not observed in the same cells stained for calnexin, an ER resident
      protein, nor in cells treated with CHX, which freezes the ribosomes to block
      protein synthesis. Our data suggest that eIF-5A does not shuttle between the
      nucleus and cytoplasm in the same way as Rev. Our findings are consistent with
      our previous conclusion that eIF-5A is associated with the ER through ribosomes
      and support a role for eIF-5A in protein synthesis.

PMID- 9285098
TI  - Cellular eukaryotic initiation factor 5A content as a mediator of polyamine
      effects on growth and apoptosis.
AB  - The polyamines are essential for eukaryotic cell growth. One of the most critical
      effects of polyamines on cell growth is the availability of spermidine for the
      post-translational modification of eIF-5A. Because hypusine-containing eIF-5A is
      necessary for cell proliferation, depletion of cellular polyamines suppresses
      growth by depleting cellular modified eIF-5A content. Excess putrescine
      accumulations in DH23A/b cells induces apoptosis and suppresses the formation of
      hypusine-containing eIF-5A. Treatment of DH23A/b cells with diaminoheptane also
      suppresses modified eIF-5A formation and induces apoptosis. These data suggest
      that suppression of modified eIF-5A formation may play a role in putrescine
      induced apoptosis as well.

PMID- 9285099
TI  - Novel features of the functional site and expression of the yeast deoxyhypusine
      synthase.
AB  - A unique amino acid, hypusine, is formed posttranslationally in the precursor of
      eukaryotic translation initiation factor 5A (eIF-5A). Deoxyhypusine synthase
      catalyzes the first of two steps in the biosynthesis of hypusine. We reported
      earlier that the DYS1 gene encoding deoxyhypusine synthase is essential for cell
      viability and proliferation in yeast. Here, we show by deletion studies that both
      N- and C-terminal regions, which are not so well conserved, are necessary for the
      activity of the yeast enzyme. Of the seven cysteine residues present in the yeast
      enzyme, only one cysteine (position 252; C252) appeared to be essential for its
      activity. Moderate overexpression of DYS1 showed very little effects on cell
      growth and no obvious effects on the intracellular level of eIF-5A. However,
      repression of the expression of DYS1 resulted in near-complete depletion of eIF
      5A 24 h after the initiation of repression and was followed by cell growth arrest
      after another 24 h. This novel finding suggests that the major role of
      deoxyhypusine synthase in cell proliferation is mediated not only through its
      modification of the eIF-5A precursor, but also through its regulation of
      intracellular eIF-5A levels.

PMID- 9285100
TI  - Interaction of eukaryotic initiation factor 5A with the human immunodeficiency
      virus type 1 Rev response element RNA and U6 snRNA requires deoxyhypusine or
      hypusine modification.
AB  - Hypusine formation on the eukaryotic initiation factor 5A (eIF-5A) precursor
      represents a unique posttranslational modification that is ubiquitously present
      in eukaryotic cells and archaebacteria. Specific inhibition of deoxyhypusine
      synthase leads to growth arrest and cell death. The precise cellular function of
      eIF-5A and the physiological significance of hypusine modification are not clear.
      Although the methionyl-puromycin synthesis has been suggested to be the
      functional assay for eIF-5A activity in vitro, the role of eIF-5A in protein
      synthesis has not been established. Recent studies have suggested that eIF-5A may
      be the cellular target of the human immunodeficiency virus type 1 Rev and human T
      cell leukemia virus type 1 Rex proteins. Motif analysis suggested that eIF-5A
      resembles a bimodular RNA-binding protein in that it contains a stretch of basic
      amino acids clustered at the N-terminal region and a leucine-rich stretch at the
      C-terminal region. Using Rev target RNA, RRE, as a model, we tested the
      hypothesis that eIF-5A may be an RNA-binding protein. We found that both
      deoxyhypusine and hypusine-containing eIF-5A can bind to the 252-nt RRE RNA, as
      determined by a gel mobility shift assay. In contrast, the unmodified eIF-5A
      precursor cannot. Deoxyhypusine-containing eIF-5A, but not its precursor, could
      also cause supershift of the Rev stem-loop IIB RRE complex. Preliminary studies
      also indicated that eIF-5A can bind to RNA such as U6 snRNA and that
      deoxyhypusine modification appears to be required for the binding. The ability of
      eIF-5A to directly interact with RNA suggests that deoxyhypusine formation of eIF
      5A may be related to its role in RNA processing and protein synthesis. Our study
      also suggests the possibility of using a gel mobility shift assay for eIF-5A-RNA
      binding as a functional assay for deoxyhypusine and hypusine formation.

PMID- 9285101
TI  - Doctors, nurses, pharmacists and patients--the Rational Evaluation and Choice in
      Hypertension (REACH) survey of hypertension care delivery.
AB  - Despite ongoing efforts by the medical profession, many hypertensive patients
      either refuse treatment or have blood pressures that are not adequately
      controlled. A key reason is likely to be the side effects of many
      antihypertensive drugs. We have investigated further reasons for stopping or
      altering antihypertensive treatment, and the patterns of prescribing in Britain
      by mounting a series of surveys amongst family doctors, practice nurses and their
      patients with hypertension. A total of 178 GPs and 158 practice nurses provided
      completed replies suitable for analysis. In addition, 948 patients were surveyed
      via their GP and 1167 were surveyed via their local pharmacist (600 unprompted,
      567 prompted). Thirty-two percent of GPs stated that hypertensive patients
      generally consulted because they were experiencing drug side effects and 42% of
      all switches of drug therapy occurred because patients experienced side effects.
      The GPs perceived that 18% of their hypertensive patients did not comply with the
      antihypertensive therapy, and, of non-compliant patients, 22% were not complying
      due to drug side effects. The 158 practice nurses reported that 29% of patients
      they saw discussed drug side effects. Hypertensive patients were more likely to
      discuss the side effects of their antihypertensive treatments with the practice
      nurse than their doctor. Forty-six percent of 948 patients who were surveyed via
      their GP did not know what antihypertensive drug class they were taking. The most
      frequently mentioned reason for patients changing medication was drug side
      effects (42%) or lack of efficacy (39%). Fifty-nine percent of patients had never
      asked about possible side effects, but 34% reported that they had experienced
      unacceptable side effects. With some prompting by pharmacists, many hypertensive
      patients would discuss their antihypertensive drugs and any side effects. This
      survey highlights the lack of communication about potential side effects between
      the doctor and hypertensive patient, and the important role of the practice
      nurse. Our survey also shows that hypertension is not being managed as
      effectively as it could be and GPs appear to be spending the majority of their
      consulting time discussing and dealing with the side effects of treatment. This,
      therefore, suggests that drugs with a cleaner side effect profile could save
      valuable GP time and resources. Better communication with patients about side
      effects is, therefore, likely to improve compliance with hypertensive treatment.

PMID- 9285102
TI  - Use and adverse reactions of antihypertensive drugs in Spain. Part I of the RAAE
      Study.
AB  - A nationwide survey, consisting of personal interviews with a representative
      sample of 2800 physicians, pharmacists, nurses, and hypertensive patients, was
      conducted to evaluate the current therapeutic management of hypertension in
      Spain. The most widely used antihypertensive drugs were angiotensinconverting
      enzyme inhibitors (36.8%), followed by calcium channel blockers (28.1%),
      diuretics (24.8%), beta-blockers (16.1%), alpha-blockers (5.2%), and alpha/beta
      blockers (4.5%). Combination drug therapy was prescribed for about 40% of
      hypertensive patients. The characteristics most highly valued by the different
      groups when selecting an antihypertensive agent are presented, as are the
      antihypertensive drugs preferred for treating high blood pressure associated with
      various pathological conditions. More than a quarter of the hypertensive patients
      surveyed (27.6%) indicated that they experienced some side effects with their
      antihypertensive medication. This, together with the failure to adequately
      control blood pressure, was the main reason that physicians cited for switching
      therapy. Approximately three-quarters of the patient respondents reported good
      compliance with their antihypertensive regimen. Physicians, however, reported
      total compliance for only 6% of their patients. Factors contributing to
      noncompliance were analysed. The implications of these results for the treatment
      of hypertension in Spain are discussed.

PMID- 9285103
TI  - Risk factor control and perceptions of risk factors in patients with coronary
      heart disease.
AB  - Treatment of hypertension and hyperlipidaemia improves cardiovascular and overall
      mortality in patients with coronary heart disease. Adequate awareness of
      atherogenic risk factors is a key first step that enables patients to address
      their risk factors. In a recently completed study in coronary heart disease
      patients at coronary angiography and 18 months later, we found that skewed views
      about atherogenic risk factors in general were expressed. In addition, awareness
      of the patients' own hypercholesterolaemia or diabetes mellitus was often
      inadequate or lacking, in contrast to their awareness of blood pressure or bad
      smoking habits. Awareness of risk factors had only marginally improved 18 months
      after the initial investigation. Smoking habits, total cholesterol, and HDL
      values had improved over 18 months but lipid values were far from reaching target
      values of accepted guidelines. A majority of our patients remained with at least
      one treatable and insufficiently controlled atherogenic risk factor, usually
      hypercholesterolaemia. Interestingly, higher awareness of risk factors correlated
      with better risk factor control. These observations suggest that systematic
      interventions are necessary to further ameliorate secondary prevention in
      coronary heart disease. Successful standardized programmes of high or perhaps
      medium intensity, that include systematic screening of risk factors, reasoned
      educational interventions, and methodical management of treatable atherogenic
      risk factors according to accepted, guidelines, therefore require further
      attention in daily medical practice.

PMID- 9285104
TI  - Patients' experiences of antihypertensive drugs in routine use: results of a
      Danish general practice survey.
AB  - A questionnaire-based survey of 1843 patients with hypertension was conducted in
      Denmark to profile patients' experiences of antihypertensive therapy. A high
      proportion of patients were found to have experienced adverse effects
      attributable to antihypertensive drug therapy. The pattern of adverse event
      reporting was consistent with the known pharmacology of the drugs prescribed.
      Thus, cold extremities were reported most often with beta-blockers and peripheral
      oedema was associated with calcium channel blockers. Patients' experiences with
      losartan indicated that this drug was tolerated better than other types of
      medication, but this finding was based on a relatively small dataset. It is
      concluded that adverse experiences attributable to antihypertensive medications
      may be a significant obstacle to the implementation of effective treatment of
      hypertension and that greater physician awareness of the problems patients
      experience may help provide hypertension therapy that is well tolerated as well
      as effective.

PMID- 9285105
TI  - Physician and patient evaluation of hypertension-related risks and benefits from
      treatment.
AB  - Implementation of management programmes in hypertension in accordance with
      current guidelines needs the participation not only of physicians and other
      health professionals, but also of the patients themselves. Patients' knowledge
      of, and attitudes to, cardiovascular risk factors, as well as patients'
      perceptions of the benefits and potential risks of treatment, are factors likely
      to be of importance regarding their compliance, their opinions and their
      acceptance of treatment. The extent to which patients are able to assess the
      absolute and relative risks of having hypertension, as well as individual
      benefits from treatment, is yet largely unexplored. Compared with a number of
      common drug treatments, the general adult population perceives the risks from
      receiving antihypertensive drug therapy as intermediate to low. Improving
      patients' knowledge and acceptance of antihypertensive therapy by improving the
      physician-patient relationship will involve patients more in their own treatment
      decisions, thereby probably improving the management and treatment as a whole.

PMID- 9285106
TI  - Treatment situation of hypertensive patients in Finnish primary health care.
AB  - OBJECTIVE: To highlight the present situation in hypertension control in Finnish
      primary healthcare. SUBJECTS AND METHODS: All health centre doctors from 30
      primary health centres were asked to record every consulting patient, pick up
      hypertensives and evaluate their blood pressure (BP) level, drug treatment, side
      effects and symptoms related to drug treatment, and compliance during 2 weeks in
      May 1995. RESULTS: In all, 337 doctors from the 30 health centres participated in
      the study. They recorded altogether 4405 hypertensive patients, of which 1209 men
      (83%) and 2311 women (87%) had drug treatment for hypertension. Of all the drug
      treated hypertensive men and women, 33% and 37%, respectively were obese (BMI >
      or = 30.0 kg/m2). Altogether, 13% of the drug-treated hypertensive men and 10% of
      women were in good control when BP < 140/90 mmHg was used as the criterion. These
      proportions doubled when BP < 160/90 mmHg and tripled when BP < 160/95 mmHg were
      applied as criteria. CONCLUSION: The proportion of drug-treated hypertensives
      under poor control is still high in Finland. Only a quarter of treated
      hypertensive patients are in good control when the criterion BP < 160/90 mmHg is
      applied.

PMID- 9285107
TI  - From the monitoring of severe to a survey of mild adverse effects of current
      antihypertensive therapy: the hidden side of the iceberg. The Scientific
      Committee of the Italian Pharmacoepidemiology Survey on Antihypertensive Therapy.
AB  - One of the most important causes of the unsatisfactory results of
      antihypertensive therapy in current medical practice is the difficulty in
      evaluating individual tolerability to the various antihypertensive agents. The
      methods commonly used, i.e. assessment in controlled studies of limited duration,
      or notification to pharmacovigilance authorities, clearly underestimate the
      problem. In order to obtain more correct information on antihypertensive
      practice, an Italian pharmacoepidemiological study has recently been planned, and
      the results of a pilot phase of this study are reported here.

PMID- 9285109
TI  - Sexual dysfunction as an obstacle to compliance with antihypertensive therapy.
AB  - Sexual dysfunction has been identified in numerous controlled trials to be a
      frequent accompaniment to antihypertensive therapy. Issues of cause and effect
      are confused because hypertension itself can cause sexual dysfunction. It seems
      probable, however, that use of certain classes of blood pressure-lowering agents,
      notably non-cardioselective beta blockers such as propranolol, thiazide diuretics
      such as chlorthalidone and centrally-acting adrenergic agonists, is associated
      with an increased risk of sexual dysfunction. The implications of these data for
      compliance with antihypertensive therapy are considered.

PMID- 9285110
TI  - Medical and cost-economy aspects of modern antihypertensive therapy--with special
      reference to 2 years of clinical experience with losartan.
AB  - Health economy is often addressed in terms of acquisition cost, i.e. the cost of
      the pill. For various reasons, mainly the stricter demands from drug regulatory
      agencies (increased development costs), novel agents must be expected to be more
      expensive than older drugs. However, if the costs of changing therapy and the
      costs induced by side effects and extra clinic visits are considered, the
      economic aspects become less of a consideration. If compliance is enhanced and
      better blood pressure control is achieved with the newer agents, then the
      therapeutic gains must be weighed against the economic aspects. Losartan, the
      first agent of the new class of angiotensin II receptor antagonists of the AT1
      type, has been available for clinical use for more than 2 years. Losartan has
      proven antihypertensive effects and its safety profile in the initial controlled
      trials (approximately 2900 patients) and in general practice (more than 14,000
      patients in Sweden) has been very good. Its effect on long-term morbidity and
      mortality has not yet been established but a large mortality endpoint trial is
      underway in hypertensive patients with cardiac hypertrophy (the LIFE trial). In
      heart failure, losartan has been shown to reduce 3-month mortality (the ELITE
      trial). Although it is too early to assess the full therapeutic benefit of
      losartan in relation to the total patient costs, its efficacy and low incidence
      of side effects has made it a useful new therapy for the treatment of
      hypertension.

PMID- 9285108
TI  - Angiotensin II antagonism: a new avenue of hypertension management.
AB  - Receptor-level blockade of angiotensin II (AII) has emerged as a new therapeutic
      principle in cardiovascular medicine. Experience with losartan, the first of the
      selective AII receptor antagonists to be approved for clinical use, indicates
      that this approach is efficacious in all grades of hypertension and offers a more
      attractive and acceptable tolerability profile than other forms of
      antihypertensive medications. Recent clinical trial data indicate that losartan
      may also be beneficial in heart failure in older patients, though the drug is not
      yet approved for this indication.

PMID- 9285111
TI  - Trace elements and superoxide dismutase in benign and malignant breast diseases.
AB  - This study was planned to determine the probable changes in trace element levels
      and superoxide dismutase (SOD) activity in women with neoplastic breast diseases.
      Measurements were performed in three different groups. The first group consisted
      of 20 healthy women, control group, the second group contained 16 patients with
      benign breast disease and the third group contained 39 patients with malignant
      breast disease. The trace element concentrations were determined by using atomic
      absorption spectrophotometry and SOD activity by using spectrophotometry. When
      compared with the control values, the plasma copper levels were slightly
      increased in the second group and significantly in the third group (p < 0.001).
      The difference between the benign and malignant groups was also significant (p <
      0.001). The red cell copper values showed a marked decrease in both groups (p < 0
      001). Although there were increases in the plasma zinc levels of both patient
      groups, the differences were not significant statistically. But, the red cell
      zinc values showed an significant increase in benign and malignant patients
      compared to the control group (p < 0.001) (p < 0.001). The plasma magnesium and
      red cell magnesium values did not show significant differences. The red cell SOD
      activity showed an significant increase in the benign and malignant patient
      groups (p < 0.001). The results of this study suggested that reactive oxygen
      metabolites may play a pathogenetic role in the both benign and malignant tumor
      development, which is reflected by the change in SOD activity, and in trace
      element concentrations.

PMID- 9285112
TI  - Lumpectomy or mastectomy? Is breast conserving surgery too expensive?
AB  - In the last decade, breast cancer patients have enjoyed an increase in breast
      conserving surgery (BCS). At present, modified radical mastectomy (MRM) and BCS
      offers equal expectations of survival. During the last few years, however, a drop
      in the frequency of BCS has been reported by several authors. Is this new trend
      due to economic concerns? To clarify the costs of breast cancer therapy (stage I
      and II), we review the literature and include a cost-utility and a cost
      minimisation analysis comparing MRM and BCS. The treatment cost (per patient) of
      BCS and MRM in Norway was calculated at $9,564 and $5,596, respectively.
      Employing a quality of life gain in BCS of 0.03 (0-1 scale) and a 5% discount
      rate, the cost per QALY in BCS compared to MRM was $20,508. In cost-minimising
      analysis, BCS and mastectomy followed by reconstructive surgery had a cost of
      $10,748 and $8,538, respectively. This indicates that BCS remains within
      reasonable cost and should not be displaced by mastectomy on economic grounds.

PMID- 9285113
TI  - Inhibition of tumor growth and metastasis by angiogenesis inhibitor TNP-470 on
      breast cancer cell lines in vitro and in vivo.
AB  - Antitumor and antimetastatic activity of the angiogenesis inhibitor O
      (chloroacetyl-carbamoyl) fumagillol (TNP-470), a semisynthetic analogue of
      fumagillin, was evaluated in breast cancer cell lines. In an in vitro MTT assay,
      after 72 hrs continuous exposure to TNP-470, growth inhibition was observed in
      all seven cell lines of murine (JYG-A, JYG-B, DD-762, and BALB/c-MC) or human
      (KPL-1, MDA-MB-231, and MKL-F) origin, in which the 50% inhibitory concentrations
      (IC50) at 72 hrs treatment were 4.6, 4.4, 4.6, 10.1, 35.0, 25.3, and 33.4
      micrograms/ml, respectively. In an in vivo assay using JYG-A, JYG-B, KPL-1, and
      MDA-MB-231 cells by orthotopic (right thoracic mammary fat pad) transplantation
      in female nude mice, TNP-470 at 30 or 50 mg/kg body weight was injected s.c.
      every other day from the day of tumor cell inoculation until the end of the
      experiment. The inhibitory effect on primary tumor growth was obtained in all
      four cell lines in a dose-dependent manner. In the 50 mg/kg TNP-470-treated
      group, the reductions in tumor weight of the JYG-A, JYG-B, KPL-1, and MDA-MB-231
      cells with respect to the controls were 50%, 30%, 4%, and 49%, respectively.
      Metastasis was seen in the JYG-A, JYG-B, and KPL-1 cells. The numbers of mice
      bearing pulmonary metastases of JYG-A and JYG-B cells and regional axillary lymph
      node metastases of KPL-1 cells were reduced, and TNP-470 at the 50 mg/kg dose to
      KPL-1 cells significantly reduced lymph node metastases compared with the
      control. Although the weight gain was retarded in the TNP-470-treated mice,
      weight loss was not seen. TNP-470 was highly effective in the treatment of breast
      cancer cells. These results suggest that the clinical use of TNP-470 may be a
      promising treatment for breast cancer patients.

PMID- 9285114
TI  - Pre-operative assessment of axillary lymph node status in patients with breast
      adenocarcinoma using intravenous 99mtechnetium mAb-170H.82 (Tru-Scint AD).
AB  - Immunoscintigraphy of the axilla has potential utility for the diagnostic and
      prognostic assessment of patients with breast adenocarcinoma. mAb-170H.82 is a
      murine monoclonal antibody (mAb) derived against synthetic Thomsen-Friedenreich
      (TF) antigen. Tru-Scint AD, a 99mTc-mAb-170H.82 immunoconjugate, has previously
      been shown to localize in various human adenocarcinomas. The purpose of this
      study was to evaluate the accuracy of this immunoconjugate in the pre-operative
      assessment of axillary lymph nodes in patients with known breast adenocarcinoma.
      Sixteen patients with documented primary breast cancer were injected
      intravenously with 1 mg of immunoconjugate (radioactivity 1.8 GBq) and imaged 22
      24 hrs post-injection. Both planar and single photon emission computed
      tomographic (SPECT) images were obtained and reviewed in a blinded fashion.
      Imaging results were compared with surgical and pathological findings. Seven of
      16 patients were found to have histologically positive axillary nodes: 5 of these
      sites were detected by immunoscintigraphy (sensitivity = 71%). Nine patients had
      pathologically disease-free axillary nodes: only 1 of these was misidentified as
      positive by immunoscintigraphy (specificity = 89%). These results suggest that
      immunoscintigraphy with 99mTc-mAb-170H.82 has promise in the detection of
      axillary lymph node involvement in patients with breast cancer. Further studies
      are warranted to define the role of immunoscintigraphy in axillary staging.

PMID- 9285116
TI  - Phase II trial of paclitaxel and ifosfamide as a salvage treatment in metastatic
      breast cancer.
AB  - PURPOSE: Treatment results in patients failing first-line chemotherapy in
      metastatic breast cancer (MBC) are still unsatisfactory, with patients exhibiting
      poor responses to salvage therapy and a short overall survival. Both paclitaxel
      and ifosfamide are able to produce objective tumor responses in this disease.
      Therefore, the antitumor effects and toxicity of their combined use could be
      worthwhile studying in patients progressing after doxorubicin-containing
      combinations. PATIENTS AND METHODS: This Phase II trial of paclitaxel/ifosfamide
      included patients with bi-dimensionally measurable metastatic breast cancer in
      second or third relapse, following anthracycline-containing regimens; ECOG PS <
      2, and adequate hepatic, cardiac, renal, and hematological functions. Paclitaxel
      175 mg/m2 was given on day 1, in a 3-hour infusion with appropriate antiallergic
      pre-medication; while ifosfamide 1.8 g/m2 was given on days 2, 3, 4 with mesna
      360 mg/m2 i.v., 15 minutes before and 4 hours after ifosfamide administration,
      and 720 mg/m2 P.O. 8 hours later at home, also on days 2, 3, 4. The cycles were
      repeated every 21 days, on an outpatient basis. RESULTS: Twenty-four patients
      were accrued for the study and 23 were considered eligible for the evaluation of
      toxicity and response. Previous chemotherapy included: CMF/FAC (16 cases); CMF
      plus mitoxantrone/FAC/cisplatin, vinblastine, mitomycin C (2 cases): and
      FAC/mitomycin C, vinblastine, and etoposide (5 cases). There were 11 (48%)
      objective responses (95% C.I.:27-69%), including 2 (9%) CR and 9 (39%) PR (95%
      C.I.:0-21% and 19-61%, respectively). Five (22%) patients attained disease
      stabilization. Median response duration was 7+ months (range 4 to 20+), and the
      median overall survival was 12 months (range 4-23+). The regimen was well
      tolerated. WHO nausea/ vomiting grades 1-2, alopecia grade 3, and neutropenia
      grades 1-2 were seen in most patients. Four patients experienced mild neuropathy,
      while it was grade 3 in 1 case. Seven patients had grade 3 neutropenia. In
      addition, grade 4 neutropenia associated with fever was documented in other 4
      cases. No hypersensitivity reactions were seen. One case of reversible
      tachycardia after drug administration was seen. Myalgia grades 1-2 was also
      reported in some patients. CONCLUSION: These results suggest that the present
      regimen has significant activity in heavily pretreated patients with a MBC, with
      a manageable toxicity profile. Further trials exploiting the above mentioned drug
      combination are warranted.

PMID- 9285115
TI  - Angiogenesis and dynamic MR imaging gadolinium enhancement of malignant and
      benign breast lesions.
AB  - PURPOSE: To determine whether dynamic magnetic resonance (MR) imaging enhancement
      parameters are associated with vessel density of malignant and benign breast
      lesions. MATERIALS AND METHODS: Forty-five patients with 48 breast lesions
      underwent gadolinium-enhanced spoiled gradient-recalled echo (SPGR) MR imaging
      followed by excisional biopsy and Factor VIII staining and vessel density
      measurement in the lesions. RESULTS: The vessel densities were not significantly
      different in 25 malignant breast lesions as compared to 23 benign breast lesions.
      Among all 48 lesions, greater MR enhancement showed an association with increased
      vessel density. Seventy-four percent of all lesions with MRI enhancement
      amplitude greater or equal to three times post-precontrast ratio had vessel
      densities greater than the median of 172 as compared to 34% of lesions with
      enhancement amplitude less than three times, p = 0.02. The rate and washout of MR
      enhancement showed no significant association with vessel density. CONCLUSION:
      Although there is an overall significant association between greater MRI
      enhancement amplitude and vessel density, MRI gadolinium enhancement of breast
      lesions is not an accurate predictor of vessel density.

PMID- 9285117
TI  - Gamma-glutamyl transpeptidase immunoreactivity in benign and malignant breast
      tissue.
AB  - GGT 129, a polyclonal antibody directed against gamma-glutamyl transpeptidase
      (GGT), was used to study GGT expression in formalin-fixed paraffin-embedded
      tissues from normal breast, 24 benign lesions, 27 in situ carcinomas or atypical
      hyperplasias, and 79 infiltrating mammary carcinomas. Epithelium of the ducts and
      ductules in normal breast tissue showed immunoreactivity along the apical
      surface. There was a strong correlation (P < 0.01) between the histologic
      classification of the tissue and GGT expression. All of the benign breast lesions
      stained positive for GGT. Among in situ carcinomas and atypical hyperplasias,
      5/27 (19%) were negative for GGT while 22/27 were immunopositive. Infiltrating
      carcinomas showed the greatest deviation from normal tissue with 23/79 (29%)
      negative for GGT. GGT expression in benign and malignant breast tissue was not
      correlated with the age of the patient, suggesting that menopausal status does
      not influence expression of GGT. Correlation of GGT immunoreactivity with tubule
      formation, nuclear pleomorphism, mitoses, grade, size of tumor, lymph node
      status, and ER/PR status was performed for 69 cases of infiltrating ductal
      adenocarcinoma. There were no statistically significant relationships between the
      level of GGT immunoreactivity and any of the parameters. The loss of GGT in some
      of the cases is evidence that this enzyme is not required for mammary tumor
      development or maintenance. However, as GGT is a component of the pathways that
      metabolize glutathione and glutathione-conjugates, the difference in levels of
      the enzyme in invasive breast cancers may be one explanation for the variation in
      chemotherapy response that has been observed in patients treated for advanced
      mammary cancer.

PMID- 9285119
TI  - Clinicopathologic analysis of amphiregulin and heregulin immunostaining in breast
      neoplasia.
AB  - We observed no association between neoplastic epithelial immunostaining for
      either amphiregulin (AR) or heregulin (HRG) and presence of ER, EGFR/ERBB-2
      overexpression, nodal status, or disease recurrence in 34 breast carcinomas.
      However, stromal cell staining for both correlated with outcome; 29% of stromal
      cell AR - cases recurred vs. 85% for AR + cases (p = 0.001), and 41% of stromal
      cell HRG - cases recurred vs. 82% of HRG + cases (p = 0.01). We conclude that
      both HRG and AR have significant biologic roles in breast carcinoma growth or
      progression via mediation of host-tumor interactions which favor aggressive tumor
      behavior.

PMID- 9285118
TI  - mdr1 mRNA expression by RT-PCR in patients with primary breast cancer submitted
      to neoadjuvant therapy.
AB  - mdr1 expression by reverse transcription and polymerase chain reaction (RT-PCR)
      has been compared to P-glycoprotein (Pgp) expression by immunohistochemistry
      (IHC) and correlated with clinical response to neoadjuvant therapy. RNA has been
      recovered from glass slide smears of fine-needle aspiration from 57 untreated
      primary breast cancers prior to neoadjuvant chemotherapy (33 cases), hormone
      therapy (23 cases), or both (1 case). Furthermore, mdr1 mRNA has been analyzed in
      6 cases after 2 months of treatment. The neoadjuvant therapy consisted of 4
      cycles of adriamycin and cyclophosphamide or tamoxifen. Of 57 tumor specimens, an
      interpretable result was obtained in 52 cases, indicating the feasibility of the
      analysis by RT-PCR with very small tumor specimens. The presence of mdr1 mRNA has
      been documented in 44/52 (84%) tumor samples with a spectrum of expression
      levels. The expression of mdr1 mRNA was compared with P-glycoprotein (Pgp)
      expression by IHC using JSB-1, 4E3, and C494 monoclonal antibodies in 48 of the
      52 interpretable tumor samples. 12/48 (25%) expressed Pgp by IHC. All tumors
      expressing Pgp by IHC were also positive by RT-PCR. The results confirm the
      higher prevalence of mdr1 mRNA compared to the protein expression. However, mdr1
      mRNA expression was found to correlate significantly with resistance to
      neoadjuvant hormone therapy only while Pgp expression detected by JSB-1
      immunostaining only correlated with chemoresistance. The lack of convincing
      correlation with chemoresistance suggests that mRNA and Pgp may not be directly
      or solely responsible for clinical response to drugs. Further studies should
      focus on the post-translational modulation of P-glycoprotein and other mechanisms
      of drug resistance.

PMID- 9285120
TI  - Transforming growth factor-beta in breast cancer: a working hypothesis.
AB  - Transforming Growth Factor-beta (TGF beta) is the most potent known inhibitor of
      the progression of normal mammary epithelial cells through the cell cycle. During
      the early stages of breast cancer development, the transformed epithelial cells
      appear to still be sensitive to TGF beta-mediated growth arrest, and TGF beta can
      act as an anti-tumor promoter. In contrast, advanced breast cancers are mostly
      refractory to TGF beta-mediated growth inhibition and produce large amounts of
      TGF beta, which may enhance tumor cell invasion and metastasis by its effects on
      extracellular matrix. We postulate that this seemingly paradoxical switch in the
      responsiveness of tumor cells to TGF beta during progression is the consequence
      of the activation of the latent TGF beta that is produced and deposited into the
      tumor microenvironment, thereby driving the clonal expansion of TGF beta
      resistant tumor cells. While tumor cells themselves may activate TGF beta, recent
      observations suggest that environmental tumor promoters or carcinogens, such as
      ionizing radiation, can cause stromal fibroblasts to activate TGF beta by
      epigenetic mechanisms. As the biological effects of the anti-estrogen tamoxifen
      may well be mediated by TGF beta, this model has a number of important
      implications for the clinical uses of tamoxifen in the prevention and treatment
      of breast cancer. In addition, it suggests a number of novel approaches to the
      treatment of advanced breast cancer.

PMID- 9285121
TI  - Physicians' preferences for information sources: a meta-analytic study.
AB  - Identification of the resources physicians use to acquire information for
      clinical practice and medical research is an important area of research for
      health sciences librarianship and medical practice. During the past twenty years
      several studies have addressed questions about physicians' preferences for
      information sources, but generalization from the results of these studies has
      been hampered by limited sampling, diverse methods, and varied reportorial
      formats. Meta-analysis provides a method for reducing these limits. Using a meta
      analytic procedure, this study reviews twelve studies published between 1978 and
      1992, categorizes and ranks the physicians' preferred information sources
      reported in each study, then aggregates and counts the frequencies of the top six
      preferences, as well as the associated first and second preferences, for all the
      study populations or their strata. The results indicate that physicians prefer to
      obtain information from journals and books, but also that they often consult
      colleagues to get answers to clinical and research questions. The implications of
      these findings for health sciences librarianship are briefly discussed.

PMID- 9285122
TI  - A basic list of recommended books and journals for support of clinical dentistry
      in a nondental library.
AB  - A basic list of 133 book and journal titles in dentistry is presented. The list
      is intended as a bibliographic selection tool for those libraries and health
      institutions that support clinical dentistry programs and services in the
      nondental school environment in the United States and Canada. The book and
      journal titles were selected by the membership of the Dental Section of the
      Medical Library Association (MLA). The Dental Section membership represents
      dental and other health sciences libraries and dental research institutions from
      the United States and Canada, as well as from other countries. The list was
      compiled and edited by the Ad Hoc Publications Committee of the Dental Section of
      MLA. The final list was reviewed and subsequently was approved for publication
      and distribution by the Dental Section of MLA during the section's 1996 annual
      meeting in Kansas City, Missouri.

PMID- 9285123
TI  - A comparison of health information on Florida's free-nets.
AB  - In the popular rush to provide electronic consumer health information,
      particularly via the Internet, one system has been largely overlooked-the free
      net. Free-nets are often text-based systems from which users choose topics from
      "menus." While the World Wide Web can be more graphically appealing, it can also
      be overwhelming. Medical information resources are available to diverse
      populations through free-nets, which are convenient, free services. The amount of
      information and range of topics they offer are vast. A study of Florida's free
      nets during a six-month period involved five free-net systems. Survey items
      included user demographics, interlibrary loan services, attitudes toward
      providing medical advice, and availability of medical librarian expertise.
      Comparisons include the number of user queries on medical and health-related free
      net menus, user-friendliness, and the type of health information provided.

PMID- 9285124
TI  - User support for a library-managed online database search service: the BMA
      Library free MEDLINE service.
AB  - This paper discusses user support in the context of a library-managed online
      database search service. Experience is drawn from the British Medical Association
      (BMA) Library's Free MEDLINE Service. More than 9,600 BMA members, who are
      largely unfamiliar with computer communications and database searching, have
      registered as users of the service. User support has played a significant role in
      the development of the service and has comprised four main aspects: an
      information pack, a help desk, online help, and MEDLINE courses. The paper
      includes an analysis of help desk usage statistics collected from January 1996
      through June 1996, and highlights other relevant research. Plans for further
      service enhancements and their implications in terms of future user support are
      discussed.

PMID- 9285125
TI  - Strategic planning with multitype libraries in the community: a model with extra
      funding as the main goal.
AB  - Medical libraries are discovering that ongoing collaboration in fundraising with
      other types of community libraries is mutually beneficial. Such partnerships may
      lead to joint grants, increase library visibility and access to decision makers,
      allow participation in community information networks, and provide leverage in
      additional fundraising projects. These partnerships have the potential to raise
      the profile of libraries. The accompanying community recognition for the parent
      organization may create a positive image, draw patients to the health center, and
      position the library and institution for future success in fundraising. Within
      institutions, development officers may become allies, mentors, and beneficiaries
      of the medical librarian's efforts. For a planned approach to community outreach
      with extra funding as the major objective, busy medical library administrators
      need guidelines. Standard participative techniques were applied to strategic
      planning by Indianapolis libraries to help achieve successful community outreach
      and to write joint statements of mission, vision, goals, and objectives.

PMID- 9285126
TI  - End-user searching: impetus for an expanding information management and
      technology role for the hospital librarian.
AB  - Using the results of the 1993 Medical Library Association (MLA) Hospital
      Libraries Section survey of hospital-based end-user search services, this article
      describes how end-user search services can become an impetus for an expanded
      information management and technology role for the hospital librarian. An end
      user services implementation plan is presented that focuses on software,
      hardware, finances, policies, staff allocations and responsibilities, educational
      program design, and program evaluation. Possibilities for extending end-user
      search services into information technology and informatics, specialized end-user
      search systems, and Internet access are described. Future opportunities are
      identified for expanding the hospital librarian's role in the face of changing
      health care management, advances in information technology, and increasing end
      user expectations.

PMID- 9285127
TI  - Mapping the literature of allied health: project overview.
AB  - The Nursing and Allied Health Resources Section of the Medical Library
      Association (MLA) created the Task Force on Bibliographic Access for the Allied
      Health Literature to identify the core journals of various allied health fields
      and assess the coverage given these titles by the major indexing and abstracting
      services. The larger objective is to influence increased bibliographic access to
      the core literature. This paper introduces the Project for Mapping the Literature
      of Allied Health and the common bibliometric methodology used for the five
      specific studies reported in the accompanying papers. Findings relating to format
      used, age of citations, dispersion of literature, and indexing coverage for the
      different fields are compared. Journals are the most heavily cited format. Fields
      differ by the currency of cited material, with physical therapy and speech
      language pathology displaying use of the oldest citations. The set of core
      journals is small for each field, particularly in speech-language pathology.
      MEDLINE provided the strongest indexing coverage overall, followed by EMBASE.
      Information such as that reported by the project can help librarians in improving
      information transfer for the allied health professionals they serve.

PMID- 9285128
TI  - Mapping the literature of health education.
AB  - Health education is a relatively new multidisciplinary field concerned with
      educational programs that empower individuals and communities to play active
      roles in achieving, protecting, and sustaining their health. Its practitioners
      have bachelor's, master's, or doctoral degrees and work in educational, worksite,
      health facility, or agency settings. This bibliometric study was part of the
      Medical Library Association (MLA) Nursing and Allied Health Resources Section's
      Project for Mapping the Literature of Allied Health. It sought to identify the
      core journals in health education and to determine the extent to which these
      titles are covered by the standard indexing sources. Cited references appearing
      from 1991 through 1993 in articles of four journals published by the major
      professional associations in the field were analyzed. It was found that only
      thirteen journals supply one-third of all references in the study. Another eighty
      journals provide the second third. MEDLINE gives the best indexing coverage with
      nearly 69% of the journals receiving indexing for at least half of their
      articles, followed by EMBASE (52%) and PsycINFO (43%). Limited coverage is given
      by the Cumulative Index to Nursing and Allied Health Literature (16%) and ERIC
      (14%). The findings name titles that should be added by indexing services and
      those that should have more complete coverage.

PMID- 9285129
TI  - Mapping the literature of physical therapy.
AB  - Physical therapy is a fast growing profession because of the aging population,
      medical advances, and the public's interest in health promotion. This study is
      part of the Medical Library Association (MLA) Nursing and Allied Health Resources
      Section's project to map the allied health literature. It identifies the core
      journals in physical therapy by analyzing the cited references of articles in two
      established physical therapy journals, Physical Therapy and Archives of Physical
      Medicine and Rehabilitation, during the period 1991 through 1993. This
      bibliometric analysis also determines the extent to which these journals are
      covered by the primary indexing sources, Allied and Alternative Medicine (AMED),
      the Cumulative Index to Nursing and Allied Health Literature, EMBASE, and
      MEDLINE. In this study, fourteen journals were found to supply one-third of all
      references studied. Ninety-five journals provided an additional third of the
      references. MEDLINE rated the highest as the indexing tool of choice for these
      109 journals. The study results can assist in collection development decisions,
      advise physical therapists as to the best access to their core literature, and
      influence database producers to increase their coverage of the literature
      important to physical therapy.

PMID- 9285131
TI  - Mapping the literature of respiratory therapy.
AB  - Little research has been conducted on the characteristics of the literature of
      respiratory care. The bibliometric method was used to identify the core journals
      in the discipline and the extent of indexing of those journals. This study was a
      part of Medical Library Association (MLA) Nursing and Allied Health Resources
      Section's project to map the literature of allied health. Findings indicate that
      the research writings of the discipline cite journal articles most heavily, with
      the majority of the citations published between 1980 and 1993. The literature has
      a small core of cited journals with a wide dispersion. MEDLINE and EMBASE
      provided the best indexing coverage of the literature, and minimal coverage was
      given by the Cumulative Index to Nursing and Allied Health Literature and HEALTH.

PMID- 9285130
TI  - Mapping the literature of radiologic technology.
AB  - While analysis of the literature of radiology has been conducted in the
      discipline, none of the studies have focused on identifying the core journals.
      The bibliometric method was used to conduct research to identify the core
      journals in the radiologic technology field and determine the extent of indexing
      of those journals. This study was a part of Medical Library Association (MLA)
      Nursing and Allied Health Resource Section's project to map the literature of
      allied health. Findings indicate that there is a small core of literature with a
      heavy reliance on the journal literature. Books are used to a lesser extent. The
      majority of the citations analyzed were published during the fourteen years
      between 1980 and 1993. MEDLINE and EMBASE provided the best indexing coverage of
      the radiologic technology literature; minimal coverage was provided by the
      Cumulative Index to Nursing and Allied Health Literature and HEALTH.

PMID- 9285132
TI  - Mapping the literature of speech-language pathology.
AB  - The purpose of this study, part of the Medical Library Association (MLA) Nursing
      and Allied Health Resources Section's project to map the allied health
      literature, is to identify the core journals in the field of speech-language
      pathology and to identify indexing and abstracting services that provide access
      to these journals. Four representative speech-language pathology journals were
      selected and subjected to citation analysis to determine which journals were
      cited and how many times each was cited. Bradford's Law of Scattering was applied
      to the resulting list of journals to identify the core journals of this
      discipline. Six indexing and abstracting services were selected and scanned to
      determine coverage for the speech-language pathology core journals. The core
      journals received broad coverage in the health sciences and social sciences
      indexing and abstracting databases surveyed, although there was no one database
      that provided complete coverage of all core journals. The full Current Contents
      database provides the most extensive coverage of core journals. For individuals
      without access to the complete Current Contents database, a combined search of
      both MEDLINE and PsycINFO provides very comprehensive coverage of core journals.

PMID- 9285133
TI  - Rachael Keller Anderson Medical Library Association President 1997-1998.

PMID- 9285134
TI  - An ethicist's commentary on the case of the bull mastiff with osteosarcoma.

PMID- 9285135
TI  - Evaluation of florfenicol for the treatment of undifferentiated fever in feedlot
      calves in western Canada.
AB  - A study was conducted in western Canada to evaluate the efficacy of florfenicol
      for the treatment of undifferentiated fever (UF) in feedlot calves. One hundred
      and twenty-five recently weaned, auction market derived, crossbred, beef steer
      calves suffering from UF were allocated to 1 of 2 experimental groups as follows:
      florfenicol, which was intramuscular florfenicol administered at the rate of 20
      mg/kg body weight at the time of allocation (day 0) and again 48 h later; or
      control, which was intramuscular saline administered at the same volume as
      florfenicol at the time of allocation and again 48 h later. Eighty-four calves
      were allocated to the florfenicol group and 41 calves were allocated to the
      control group. Outcome measures describing animal health, body weight, and rectal
      temperature parameters were used to determine the efficacy of florfenicol for the
      treatment of UF. The 1st relapse of UF, 2nd relapse of UF, overall mortality,
      bovine respiratory disease mortality, and haemophilosis mortality rates were
      significantly (P < 0.05) lower in the florfenicol group than in the control
      group. Animals in the florfenicol group were significantly (P < 0.05) heavier at
      day 15 and day 45 than animals in the control group. The rectal temperature on
      days 1, 2, 3, and 4 of animals in the florfenicol group was significantly (P <
      0.05) lower than in the control group. In addition, the change in rectal
      temperature from day 0 to day 4 was significantly (P < 0.05) different between
      the experimental groups. The results of this study demonstrate that florfenicol
      is an efficacious antimicrobial for the treatment of UF.

PMID- 9285136
TI  - Management of a transverse fracture in the distal phalanx of a horse.
AB  - A yearling horse was presented with a septic, transverse fracture in the frontal
      plane of the distal phalanx. The fracture fragment was surgically removed from
      the parent bone via the sole. The foot was managed by corrective farriery and the
      horse was able to be ridden for pleasure.

PMID- 9285137
TI  - Assessment of 3 audible monitors during hypotension in anesthetized dogs.
AB  - Severe hypotension was produced in 8 dogs during halothane anesthesia. Three
      monitors detecting respiratory rate, Doppler signal and pulse rate were compared
      to direct blood pressure measurements. Deep anesthesia was most consistently
      detected using the respiratory monitor. The signal fade of the Doppler device was
      best at detecting hypotension from blood loss. Changes in heart rate were not
      useful.

PMID- 9285138
TI  - Pseudocyst of the spermatic cord of a gelding.
AB  - Clinical, echographic, and histopathological features of an unusual enlarging
      scrotal mass in a 5-year-old gelding are described. Echography of the scrotal
      mass in this case provided valuable information concerning the nature of the
      tissue present, and assisted in narrowing the differential diagnosis.

PMID- 9285139
TI  - Multiple aneurysmal bone cysts in a foal.
AB  - Multiple aneurysmal bone cysts (ABCs) are previously unreported in horses. An ABC
      was diagnosed in the left 3rd metacarpal of a Thoroughbred foal, which partially
      resolved following surgical curettage. A 2nd ABC developed in the left tibia, 7
      wk postoperatively, and the foal was euthanized.

PMID- 9285140
TI  - Repair of a comminuted femoral fracture in a cat using cortical and cancellous
      bone grafting techniques.

PMID- 9285141
TI  - Edward Watson and the eradication of dourine in Canada.

PMID- 9285142
TI  - Mucosal immunity in the urinary tract: changes in sIgA, FSC and total IgA with
      age and in urinary tract infection.
AB  - The incidence of primary urinary tract infection (UTI) is greatest in the first
      month of life and decreases with age throughout childhood. Secretory
      immunoglobulin A (sIgA) is an important component of mucosal immunity. The
      changes in secretory IgA, IgA and free secretory component (FSC) during the first
      year of life were examined in relation to age, sex and in infants, feeding
      practice. These constituents were further compared between healthy children and
      those with acute and recurrent UTI. Urine was collected from 41 healthy infants
      (16 female: 25 male) at intervals (mean age 1.4, 9.1, 44, 91, 210 and 412 days),
      139 healthy children (75 female: 64 male), 29 children with histories of
      recurrent UTI (25 female: 4 male) and 10 with acute UTI (8 female: 2 male). sIgA,
      IgA and FSC were measured by enzyme linked immunoassay. In the majority of
      children sIgA and IgA were undetectable at birth. SIgA and IgA rose significantly
      during the first year then levelled off throughout childhood. FSC was detectable
      from birth (geometric mean [mean of logged values]-GOM at day 1.4, 362.2 ng/ml).
      No sex differences were apparent for any of the three constituents at any age.
      Breast feeding was associated with higher levels of sIgA and IgA than bottle
      feeding. This was highly significant at 9.1 days when sIgA and IgA levels of
      breast fed compared with bottle fed infants were 64.6 ng/ml vs 21.2 and 56.2
      ng/ml vs 18.7 ng/ml respectively, giving a GOM ratio of 3.04 for sIgA and 3.0 for
      IgA (p < 0.001 for both). No significant difference in the three parameters were
      demonstrable when children with recurrent UTI-with normal or abnormal renal
      tracts-were compared with controls. Acute UTI resulted in raised sIgA, IgA and
      FSC compared with controls (GOM ratio of 4.9 [p < 0.002], 4.2 [p < 0.005] and 2.7
      [p < 0.001] respectively). The proportion of total IgA present as sIgA
      (sIgA/total IgA) was not significantly different in the acute vs control groups.
      Urinary sIgA and IgA may be important for the observed variation with age in
      infant UTI and the reduced incidence in breast fed infants but does not appear to
      contribute to the sex associated difference in susceptibility to infection at any
      age.

PMID- 9285143
TI  - Urinary IgG excretion as a prognostic factor in idiopathic membranous
      nephropathy.
AB  - In membranous nephropathy it would be of great value to be able to identify in an
      early phase patients at highest risk for disease progression, since potentially
      toxic treatment could then be restricted to these patients only. We measured
      renal hemodynamics, serum proteins and urinary protein excretion in 22 patients
      with membranous nephropathy, nephrotic syndrome and normal renal function
      (endogenous creatinine clearance > 85 ml/min). These patients were followed for a
      mean of 56 months. Renal function deteriorated in nine patients. When using
      univariate analysis, deterioration of renal) function appeared to be associated
      with a low serum albumin and transferrin, high urinary transferrin, beta
      microglobulin, and IgG excretion, but not with renal hemodynamics. A step-up
      procedure, used for selecting variables associated with survival, showed that IgG
      excretion was independently associated with renal function deterioration. In
      patients with membranous nephropathy and normal renal function, the urinary
      excretion rate of IgG predicts future renal function outcome.

PMID- 9285144
TI  - Soluble intercellular adhesion molecule-1 (ICAM-1) in serum and urine:
      correlation with renal expression of ICAM-1 in patients with kidney disease.
AB  - A soluble form of intercellular adhesion molecule-1 (sICAM-1) has been described
      in serum and other body fluids. In order to determine whether sICAM-1 in serum
      and urine is a useful marker of inflammatory activity in kidney diseases we
      measured sICAM-1 in serum and urine of fifty patients who underwent renal biopsy,
      and of twenty healthy individuals. Expression of ICAM-1 on proximal tubular
      epithelial cells was investigated by immunohistochemistry. Soluble ICAM-1 in
      serum did not differ between patients and controls (354 +/- 129 ng/ml vs. 305 +/-
      52 ng/ml). By multiple regression analysis sICAM-1 correlated with tubular
      expression of ICAM-1 (p < 0.01), but not with serum creatinine, infiltrating
      leukocytes, urinary ICAM-1 or proteinuria. In healthy controls mean urinary ICAM
      1/cr was 2.5 +/- 3.0 ng/mg creatinine and differed significantly from that of
      patients (14.5 +/- 14.9 ng/mg) (p < 0.005). Patients with minimal-change disease
      had the highest uICAM-1 levels. The ratio of urinary ICAM-1 and proteinuria was
      remarkably constant in all patients with 6.0 +/- 0.9 ng/mg. By multiple
      regression analysis uICAM-1/cr correlated with proteinuria/cr (p < 0.001) and
      sICAM-1 (p < 0.005). These data show that sICAM-1 does to some degree reflect
      ICAM-1 expression in the kidney, whereas uICAM-1 is derived from glomerular
      filtration and closely parallels proteinuria. Both sICAM-1 and uICAM-1 are not
      useful to estimate ICAM-1 expression and inflammatory activity in the kidney.

PMID- 9285145
TI  - Microalbuminuria as a predictor of a drop in glomerular filtration rate in
      subjects with non-insulin-dependent diabetes mellitus and hypertension.
AB  - Hypertension and non-insulin-dependent diabetes mellitus (NIDDM) are two major
      risk factors for end-stage renal failure. The value of microalbuminuria (urinary
      albumin excretion [UAE]: 30-300 mg/24 h) as an indicator of the glomerular
      filtration rate (GFR) is not known in these patients. METHODS: The relationships
      between microalbuminuria and GFR in subjects with NIDDM and hypertension were
      studied cross-sectionally (Study I) and longitudinally (Study II). RESULTS: In
      study I, 205 NIDDM subjects with hypertension (151 with normoalbuminuria [UAE <
      30 mg/24 h] and 54 with microalbuminuria) were studied. The GFR of subjects with
      normoalbuminuria (97 +/- 30 ml/min) (mean +/- SD), and microalbuminuria (97 +/-
      27 ml/min; NS) were similar. Study II examined 51 of the subjects with
      normoalbuminuria and 21 with microalbuminuria 22 months (range 13-57) later. The
      GFR of subjects with microalbuminuria (-10 +/- 19 ml/min) declined more than in
      those with normoalbuminuria (+4 +/- 17 ml/min; Student's t-test: p = 0.0022). The
      predictive value of microalbuminuria for a drop in GFR was independent of the
      antihypertensive treatment used, the follow-up time, or changes in UAE. The only
      variable linked to GFR loss in subjects with microalbuminuria was an increase in
      diastolic blood pressure (p = 0.0298). CONCLUSION: Microalbuminuria is a risk
      factor for a drop in GRF in NIDDM subjects with hypertension, and a reduction in
      blood pressure is the only effective way to prevent a loss of GFR in subjects
      with microalbuminuria.

PMID- 9285147
TI  - Cystatin C measurement and its practical use in patients with various renal
      diseases.
AB  - OBJECTIVE: To evaluate the clinical usefulness in terms of estimation for
      glomerular filtration rate (GFR), we determined the cystatin C levels in the
      serum and urine of 33 healthy volunteers as well as in the serum and urine of 35
      patients with various renal diseases and compared them with those of creatinine.
      In addition, we evaluated this substance as an indicator of removal rate of low
      molecular weight protein with high flux membranes in 6 hemodialysis (HD)
      patients. METHODS: Serum and urinary cystatin C levels were measured by using an
      enzyme-linked immunosorbent assay (ELISA) method, 24-hour creatinine clearance
      was used as an indicator of GFR. RESULTS: Reference intervals with 95% ranges are
      0.47-1.03 mg/l in the serum from healthy volunteers. There was a significant
      positive correlation between serum cystatin C and creatinine levels (r = 0.936, p
      < 0.001) in the patients with various renal diseases. Serum cystatin C and
      creatinine inversely and logarithmically correlated to creatinine clearance as
      shown in the following equations: log cystatin C = -0.564 x log creatinine
      clearance + 1.216 (r = -0.850), log creatinine = -0.678 x log creatinine
      clearance + 1.449 (r = -0.904). In these equations l/day is the unit used for
      creatinine clearance, mg/l is the unit used for serum cystatin C. The range for
      cystatin C is 0.67-6.15 mg/l, 0.66-7.23 mg/dl for creatinine and 8.9-186.3 l/day
      (6.2-129.4 ml/min) for creatinine clearance. Serum cystatin C levels started to
      increase over normal range when creatinine clearance fell below 135.9 l/day (94.4
      ml/min), while serum creatinine remained within normal ranges. The daily urinary
      excretion of cystatin C was increased significantly in the group in which
      creatinine clearance was below 30 l/day (20.8 ml/min) compared to that in which
      creatinine clearance was higher than in 70 l/day (48.6 ml/min). Fractional
      clearance of cystatin C increased proportionally and markedly to the decrease of
      creatinine clearance. In a regular HD condition with high flux membrane, the
      cystatin C removal rate was 38.7 +/- 1.7%. CONCLUSIONS: These data suggest that
      combined measurement of cystatin C in the serum and urine is useful to estimate
      GFR, especially to detect the mild reduction of GFR. Cystatin C measurement can
      also be used as an indicator of removal rate of low molecular weight protein with
      different types of high flux membranes in hemodialysis.

PMID- 9285146
TI  - Relationship between blood pressure and renin, angiotensin II and atrial
      natriuretic factor after renal transplantation.
AB  - The objective of the study was to assess the evolution of renin, angiotensin II,
      atrial natriuretic factor (ANF) and blood pressure (BP) in the first trimester
      following renal transplantation in man Thirty-two recipients were investigated
      for 3 months post-transplantation. Twenty had a history of hypertension with
      moderate cardiac hypertrophy. Thirty-one retained their native kidneys. Five
      kidney donors had a history of mild hypertension. The recipients were
      perioperatively volume-expanded with 0.9% saline and diuresis was maintained for
      48 h with furosemide and dopamine. The sodium intake was 25 mEq/24 hours.
      Prophylactic immunosuppressive therapy was antilymphocyteglobulins (25 cases), or
      anti-LFA1 (7 cases) and maintenance therapy was cyclosporine-prednisone (8
      cases), or cyclosporine-prednisone-azathioprine (24 cases). Mean BP, serum
      creatinine, urinary sodium excretion (UNA) and hormonal (renin, angiotensin II
      and ANF) parameters were collected every other day for the first week after
      transplantation and then twice monthly. Twenty (62.5%) patients developed
      hypertension and hypertension was more frequent in patients with a delayed graft
      function, than in patients with immediate good graft function (10/20 vs. 4/12, p
      < 0.05%). Both hypertensive (group HBP) and normotensive (group NBP) patients had
      similar very low renin and angiotensin II plasma levels, after an initial early
      peak. Analysis of covariance with multiple regression analysis showed that in the
      HBP patients, BP was negatively correlated with UNA (p = 0.02) and positively
      with plasma ANF (p < 0.01). The normal BP patients also showed a correlation
      between BP and UNA, although it was limit of statistical significance (p = 0.05);
      there was no correlation between ANF and BP. We conclude that the RAS is rapidly
      depressed after renal transplantation and does not interfere with BP regulation.
      The hypertension in the early stage of post-transplantation varies inversely with
      the urinary sodium excretion. The defective sodium excretion, which dominates the
      effect of the low sodium diet, results in volume overload, increased ANF and
      volume-dependent hypertension.

PMID- 9285148
TI  - Intravenous alfacalcidol improves insulin resistance in hemodialysis patients.
AB  - We have examined the effect of a four-week intravenous treatment with 1 alpha
      hydroxyvitamin D3 on insulin sensitivity in 14 patients on chronic hemodialysis
      compared with 10 healthy control subjects by the insulin tolerance test. Compared
      to controls, the uremic patients have featured increased levels of parathyroid
      hormone (1085.0 +/- 822.1 vs 74.2 +/- 8.7 pg/ml, p < 0.001), insulin resistance
      (the rate constant for plasma glucose disappearance, K(in): 3.1 +/- 0.5 vs 4.5 +/
      0.4%/dk, p < 0.002), increased levels of insulin (30.5 +/- 7.3 vs 20.4 +/- 2.8
      microIU/ml, p < 0.04) and increased levels of C-peptide (6.0 +/- 2.1 vs 3.9 +/-
      12, ng/ml, p < 0.001). Following treatment with 1 alpha-hydroxyvitamin D3, levels
      of parathyroid hormone decreased from 1085.0 +/- 822.1 to 772.1 +/- 620.1 pg/ml
      (p < 0.004), the K(in) values increased significantly (from 3.1 +/- 0.5 to 4.1 +/
      0.4%/dk, p < 0.004) and reached the level near to that of controls, the insulin
      concentrations decreased from 30.5 +/- 7.3 to 28.7 +/- 9.2 microIU/ml (p > 0.05)
      and C-peptide concentrations increased from 6.0 +/- 2.1 to 7.5 +/- 2.5 ng/ml (p <
      0.02). In summary, uremic patients with secondary hyperparathyroidism developed
      insulin resistance and hyperinsulinemia. Intravenous 1 alpha-hydroxyvitamin D3
      treatment has improved insulin sensitivity directly or by reducing secondary
      hyperparathyroidism in uremic patients on chronic hemodialysis.

PMID- 9285149
TI  - Increasing numbers of AV fistulas for hemodialysis access.
AB  - As part of our CQI program, we initiated an effort to see if we could
      successfully increase the total number of native arterio-venous (AV) fistulas
      relative to synthetic PTFE grafts in our dialysis population. This was a combined
      effort of the nephrology and surgery departments. The program emphasized
      placement of brachial fistulas in elderly patients and diabetics. Permcaths were
      placed in the internal jugular position to allow adequate time for maturation of
      fistulas. The percentage of AV fistulas in our total dialysis population
      increased from 28% (93 of 328) in the base period 1990 through 1992 to 44% (170
      of 386) in the period from 1993 through 1995 (p < 0.0001). Initial AV fistula
      insertions increased from 38% (52 of 137) in 1990-1992 to 71.8% (102 of 142) in
      the years 1993 through 1995 (p < 0.0001). 86.5% (45 of 52) of initial fistulas
      placed in 1990-1992 were useable compared to 63.7% (65 of 102) in 1993-1995 (p <
      0.01). Patient demographics were unchanged throughout the study. In conclusion,
      the number and percentage of AV fistulas in our dialysis population was
      significantly increased through a coordinated CQI initiative. We expect that this
      will have a positive impact on decreasing future thrombosis rates and decreasing
      the cost of access management.

PMID- 9285150
TI  - Cast nephropathy in mu heavy chain disease.
AB  - The occurrence of kidney diseases was very rarely reported in heavy chain
      diseases (HCD). At variance with gamma and alpha HCD in which there is no free
      light chain secretion, about two-thirds of mu HCD patients have urinary Bence
      Jones (BJ) proteins. We report on a 66 year-old man affected with typical mu HCD
      who developed renal failure after a 3-year follow-up. He had presented with
      chronic lymphocytic leukemia with bone marrow vacuolated plasma cells, serum mu
      HCD protein and serum and urine BJ protein. After an apparent hematological
      remission following fludarabine therapy, anemia and blood hyperlymphocytosis
      recurred together with microscopic hematuria, proteinuria and increased
      creatininemia. Kidney biopsy showed numerous tubular eosinophilic casts which
      stained for kappa chain determinants by immunofluorescence and an interstitial
      infiltration by lymphocytes and plasma cells. The hematological and renal
      condition improved after reinitiation of chemotherapy. This appears to be the
      first documented report of a light chain-dependent visceral complication in HCD.

PMID- 9285151
TI  - Postoperative acute pulmonary edema: a rare presentation of pheochromocytoma.
AB  - A 39-year-old white female underwent an uneventful vaginal hysterectomy for
      dysfunctional bleeding. Evaluating a mild aortic insufficiency murmur
      preoperatively an echocardiogram revealed normal left ventricular wall motion and
      function. Postoperatively the patient developed severe abdominal pain, acute
      hypertension (200/100 mmHg), and sinus tachycardia. Within minutes she
      decompensated into acute pulmonary edema. ECG demonstrated acute ST segment
      elevation in the precordial leads consistent with acute infarction. Emergency
      left heart catheterization showed normal coronary vessels with severe left
      ventricular dysfunction. An abdominal ultrasound was obtained, revealing a right
      adrenal mass. Plasma epinephrine was 334, norepinephrine 34,543 pg/ml; urine
      epinephrine 45, urine norepinephrine 2,137 micrograms/24 hours. She was started
      on prazosin and nifedipine sustained release with good blood pressure control.
      Four days later, an echocardiogram demonstrated the left ventricular wall motion
      reverting to normal. The adrenal tumor was subsequently resected successfully.
      Acute pulmonary edema causing dilated cardiomyopathy is a rare complication of
      pheochromocytoma that has been seldomly reported. A progressive fatal course is
      common: reversibility and survival depend on identifying and removing the
      pheochromocytoma.

PMID- 9285152
TI  - Urinary obstruction causes irreversible renal failure by inducing chronic
      tubulointerstitial nephritis.
AB  - Obstruction of urinary tract is a frequent cause of transient renal dysfunction,
      which, in the majority of cases, is reversible. Urinary obstruction can
      occasionally cause chronic renal failure, in spite of successful relief of the
      obstruction. Sonographic and pathologic studies show renal atrophy, interstitial
      fibrosis, and interstitial inflammation, which explain the loss of renal
      function. Herein, we report two cases of bilateral obstructive nephropathy due to
      prostatic hyperplasia, in which renal ultrasound demonstrated hydronephrosis and
      normal cortical thickness. In both cases, the renal failure persisted even after
      urinary obstruction was relieved by continuous catheter drainage. Renal biopsy
      showed that in each case the cause of the irreversible renal failure was chronic
      tubulointerstitial nephritis. It is concluded that renal biopsy can be of
      diagnostic, as well as of prognostic value in obstructive nephropathy, especially
      when relief of the obstruction is not followed by restoration of the renal
      function.

PMID- 9285154
TI  - Paracetamol-induced pancreatitis and fulminant hepatitis in a hemodialysis
      patient.
AB  - The occurrence of hepatotoxicity and acute renal dysfunction following an acute
      paracetamol overdose has been well documented. Acute pancreatitis, however, has
      been rarely described. We would like to report a hemodialysis patient who
      developed acute pancreatitis and hepatic failure from acute paracetamol toxicity.
      To our knowledge, this represents the first description in a dialysis patient of
      paracetamol induced pancreatitis. Given the frequency of paracetamol usage in
      these patients, we believe that it is important to consider this diagnosis in
      patients with unexplained acute pancreatitis, particularly if there is associated
      hepatic dysfunction.

PMID- 9285153
TI  - Primary pancreatic non-Hodgkin's lymphoma in a renal transplant recipient.
AB  - Primary pancreatic non-Hodgkin's lymphoma (NHL) is rare and accounts for less
      than 1% of all lymphomas. The development of NHL following transplant is well
      recognized. However, there are no previous reports on localized lymphomatous
      pancreatic involvement in a transplant patient. We report on the first case of
      primary pancreatic NHL developing in a renal transplant recipient. The patient
      was treated without reducing immunosuppression and received combination
      chemotherapy and radiation. The patient is in complete remission at 10-month
      follow-up.

PMID- 9285156
TI  - Urinary beta-glucuronidase excretion in insulin-dependent diabetes mellitus:
      relation with diabetic nephropathy.

PMID- 9285155
TI  - de-novo Alport syndrome: for the diagnosis of inherited glomerulonephritis with
      neither any family history nor extrarenal manifestation.

PMID- 9285157
TI  - Antibiotics update.
AB  - Some of the newer antimicrobial agents that have either appeared on the market,
      will probably soon appear, or that are being used in other parts of the world and
      are therefore worthy of our interest will be reviewed. The agents reviewed fall
      into the following four classes: antibacterial, antifungal, antiparasitic, and
      antiviral.

PMID- 9285158
TI  - Office evaluation of the child with hematuria.
AB  - Most children with an identifiable cause of hematuria will be properly diagnosed
      if an appropriate evaluation is completed. However, some children with persistent
      hematuria will not have an identifiable cause. This article provides clinical
      advice on properly diagnosing the child.

PMID- 9285159
TI  - Understanding family relationships in the late 1990s.
AB  - No one marries only an individual. Each marries the partner plus his or her kin,
      parents, grandparents, and siblings. Marriage and inlaws are discussed.

PMID- 9285160
TI  - Diagnosis & management of pituitary tumors.
AB  - Pharmacologic agents are useful in the management of some patients with pituitary
      tumors. The diagnosis and management of pituitary adenomas are discussed.

PMID- 9285161
TI  - Primary care issues for the breast cancer survivor.
AB  - The care of women treated for breast cancer is not only a responsibility of
      medical oncologists, radiation oncologists, and surgeons, but also of primary
      care physicians. Primary care and quality-of-life issues unique to the breast
      cancer survivor are discussed.

PMID- 9285162
TI  - Medical & surgical approaches to pulmonary hypertension.
AB  - When no other explanation for pulmonary hypertension can be found, it is referred
      to as primary pulmonary hypertension (PPH). Causes of pulmonary hypertension,
      with a special focus on PPH, as well as recent advances in both its medical and
      surgical treatment of pulmonary hypertension are reviewed.

PMID- 9285163
TI  - Carvedilol [Coreg].

PMID- 9285164
TI  - FDA clears Siemens' Opdima digital mammography biopsy & spot imaging system for
      U.S. marketing.

PMID- 9285165
TI  - UCSF gene discover opens new window on mechanism of yeast infection.

PMID- 9285166
TI  - Duke researchers link brain tumor drug resistance to mismatch repair deficiency.

PMID- 9285167
TI  - Guidelines on sodium lauryl sulfate (SLS) exposure tests. A report from the
      Standardization Group of the European Society of Contact Dermatitis.
AB  - This report reviews the clinical and histopathological reactions caused by sodium
      lauryl sulfate (SLS), and the non-invasive methods that can characterize these
      reactions. Furthermore, SLS exposure techniques and factors that may influence
      the outcome of these exposures are discussed. Finally, guidelines are introduced
      for each exposure technique in order to have a uniform approach to SLS testing in
      man. Since different study aims warrant different testing conditions, we have
      proposed 2 categories, namely susceptibility testing and provocative testing,
      tailored to the aim with which the study is performed.

PMID- 9285168
TI  - Bulb dermatitis. Dermatological problems in the flower bulb industries.
AB  - The irritant and allergenic properties of the most important flower bulbs are
      described, as well as the clinical symptoms they cause. The tulip contains the
      allergen tulipalin A; sensitization and irritation are responsible for the
      development of tulip fingers. The same clinical picture can be caused by Alliums
      like the onion and garlic. The narcissus causes lily rash, a dermatitis rarely
      caused by sensitization. The hyacinth evokes itching in practically everyone: an
      irritant reaction caused by calcium oxalate crystals. Patch testing is
      complicated as the allergens are not all identified.

PMID- 9285170
TI  - Cross-reaction patterns in patients with contact allergy to simple methylol
      phenols.
AB  - The low-molecular-weight phenols 2-methylol phenol (2-MP), 4-methylol phenol (4
      MP), 2,4,6-trimethylol phenol (2,4,6-MP), 3-methylol phenol (3-MP), 2,4
      dimethylol phenol (2,4-MP), and 2,6-dimethylol phenol (2,6-MP) are contact
      sensitizers in resins based on phenol and formaldehyde (P-F-R). Other chemically
      related low-molecular-weight phenols are common in the environment. In patients
      hypersensitive to P-F-R and MPs, it is for diagnostic, therapeutic and preventive
      reasons necessary to know their cross-reaction patterns, which this study was
      therefore designed to investigate. In patients with contact allergy to a P-F-R
      and at least 1 MP, additional patch testing was performed with 6 MPs and 13
      chemically related compounds. The 19 substances were tested at equimolar
      concentrations and in serial dilutions. Investigations by high-performance liquid
      chromatography were carried out to exclude contamination as the cause of the
      patch test reactions. Probable cross-reacting substances were o-cresol, p-cresol,
      salicylaldehyde, 2,4-dimethyl phenol, and 2,6-dimethyl phenol.

PMID- 9285169
TI  - Contact allergy to gold sodium thiosulfate. A comparative study.
AB  - During 1995, we added gold sodium thiosulfate and potassium dicyanoaurate to the
      patch test standard series. Our purpose was to compare the reactivity of the gold
      salts, to determine the frequency of contact allergy to gold in our country, to
      compare our results with those of the Malmo group and, finally to try to clarify
      the clinical relevance 2853 patients were routinely tested and 168 patients
      answered a questionnaire similar to that used by the Malmo group. Contact allergy
      to gold was found in 23 patients, all women: 22 to gold sodium thiosulfate
      (0.78%), only 1 to potassium dicyanoaurate and 2 to both salts. All reactors had
      their ears pierced and were exposed to gold jewelery (mainly earrings).
      Simultaneous allergies to nickel and cobalt were statistically significant in
      patients with positive patch tests to gold sodium thiosulfate. Atopy was no more
      common among these patients.

PMID- 9285171
TI  - Is patch testing necessary in vulval vestibulitis?
AB  - Allergic contact dermatitis has been suggested as a possible cause of vulval
      vestibulitis, a condition of unknown aetiology characterized by burning, stinging
      and dyspareunia, with symptoms localised to the vestibule. To examine this
      relationship, 30 women with vulval vestibulitis were patch tested using a
      standard series of contact allergens and a special series relevant to perianal
      and vulval disorders. Other potential allergens identified by the patients as
      causing aggravation were also included. There were 5 positive reactions, 4 to
      nickel and 1 to fragrance mix, though none of these reactions were considered
      relevant. Our results suggest that allergic contact dermatitis is unlikely to be
      a primary factor in the development or persistence of vulval vestibulitis. Patch
      testing patients with vulval vestibulitis cannot routinely be recommended.

PMID- 9285172
TI  - Contact dermatitis due to 1,3-butylene glycol.

PMID- 9285173
TI  - Occupational contact dermatitis due to pyritinol.

PMID- 9285174
TI  - Induction of contact sensitization to monotertiary butyl hydroquinone.

PMID- 9285175
TI  - Photosensitivity due to doxycycline hydrochloride with an unusual flare.

PMID- 9285176
TI  - Contact dermatitis from didecyldimethylammonium chloride and bis-(aminopropyl)
      lauryl amine in a detergent-disinfectant used in hospital.

PMID- 9285177
TI  - Plasma endothelin-1 levels in non-insulin dependent diabetes mellitus patients
      with macrovascular disease.
AB  - BACKGROUND: Endothelin-1 (ET-1) with its well-known vasoconstrictive and
      mitogenic action and through its interaction with insulin, blood glucose, and
      lipids might play an important role in the accelerated atherogenic process in
      diabetes mellitus. OBJECTIVE: To determine whether ET-1 levels are indicative of
      macrovascular disease in diabetes mellitus. METHODS: In the present cross
      sectional study, plasma ET-1 concentrations were measured in members of three
      groups. The first group consisted of 20 patients (15 men and five women; aged
      56.3 +/- 12.5 years) with non-insulin-dependent diabetes mellitus and coronary
      artery disease, the second group of 20 patients (16 men and four women, aged 56.9
      +/- 11.2 years) with coronary artery disease only, and the third group of 10
      healthy subjects who served as controls. ET-1 levels were determined by a
      radioimmunoassay. RESULTS: The mean plasma ET-1 levels for the three groups were
      3.59 +/- 1.88, 4.31 +/- 1.32, and 4.42 +/- 1.01 pmol/l respectively, and there
      was no statistically significant difference among the groups (P = 0.23). There
      was also no correlation between the plasma ET-1 concentration and age, sex, body
      mass index, triglyceride, total cholesterol, high-, low- and very-low density
      lipoprotein levels, for all groups, and, for the first group, hemoglobin A1c
      (HbA1c), the duration of diabetes mellitus. CONCLUSION: The plasma ET-1
      concentration is not elevated in non-insulin-dependent diabetes mellitus patients
      with macrovascular disease, which might reflect the fact that its action occurs
      in a paracrine or an autocrine rather than an endocrine fashion and suggests that
      ET-1 levels are not necessarily indicative of macrovascular disease in diabetes
      mellitus.

PMID- 9285178
TI  - Wall thickening at rest and contractile reserve early after myocardial
      infarction: correlation with myocardial perfusion and metabolism.
AB  - BACKGROUND: Abnormalities in wall thickening and their reaction to stimulation
      can be studied by magnetic resonance imaging. OBJECTIVE: To analyse the
      relationship between these abnormalities and changes in myocardial perfusion and
      fatty acid metabolism. METHODS: Fifteen patients with a myocardial infarction
      underwent low-dose dobutamine magnetic resonance imaging to assess their wall
      thickening and contractile reserve, and technetium-99m sestamibi (MIBI) and beta
      methyl-iodophenyl-pentadecanoic acid (BMIPP) single-photon emission tomography to
      assess their myocardial perfusion and fatty acid uptake. For nine segments per
      patient, the wall thickening was scored as normal, hypokinetic or akinetic, and
      the myocardial perfusion as normal (> 65%), mildly to moderately reduced (35-65%)
      or severely reduced (< 35%). Abnormalities in fatty acid uptake were compared
      with the myocardial perfusion and defined as matched (difference < or = 10%) or
      mismatched (difference > 10%) reduction. RESULTS: Thirty-four segments had
      abnormal wall thickening (13 hypokinetic and 21 akinetic). The wall thickening at
      rest was significantly related to the uptake of MIBI (P < 0.001), but not to
      abnormalities in the uptake of BMIPP. All of the akinetic segments had an
      abnormal uptake of MIBI (15 severely and six mildly to moderately reduced),
      whereas 7 of 13 hypokinetic segments had a normal and five a midly to moderately
      reduced uptake. A significant relationship between abnormalities of fatty acid
      metabolism and the contractile reserve was also found (P < 0.002): 14 of 16
      segments with and only six of 18 without contractile reserve had a mismatched
      reduction in uptakes of MIBI and BMIPP. CONCLUSION: This study confirms the
      relationship between the wall thickening at rest and the residual perfusion after
      infarction. On the other hand, the contractile reserve, which is an accepted
      indicator of the viability of the infarct region, is associated strongly with
      abnormalities of fatty acid metabolism.

PMID- 9285179
TI  - Intravascular ultrasound assessment of direct percutaneous transluminal coronary
      angioplasty in patients with acute myocardial infarction.
AB  - BACKGROUND: Acute myocardial infarction is caused by sudden thrombotic occlusion
      of the coronary artery due to a previous rupture of atherosclerotic plaque.
      OBJECTIVE: To use intracoronary ultrasound measurements to evaluate lumen and
      plaque changes in patients with acute myocardial infarction. METHODS: Patients (n
      = 103) with acute myocardial infarction who had been scheduled to undergo primary
      percutaneous transluminal coronary angioplasty (PTCA) were selected. Both before
      and after successful coronary angioplasty, intracoronary 30 MHz ultrasound
      studies were performed using a 3.5F monorail catheter. The ultrasound catheter
      was successfully advanced into the occluded vessel segment without major
      complications prior to PTCA in 79 of 103 (76.7%) patients and after PTCA in 88 of
      103 (85.3%) patients. RESULTS: The plaques were eccentric in 66 patients (83.5%).
      The plaque morphology was purely low echogenic in 14 (17.7%), highly echogenic in
      six (7.6%) and mixed in 59 (74.7%) patients. Partial (59 of 79, 74.7%) or ring
      like calcification (3 of 79, 3.8%) was observed in 62 patients (78.5%). Plaque
      fissuring or dissection was detected prior to PTCA in 25 patients (31.7%).
      Coronary angioplasty successfully enlarged the inner luminal area from 2.1 +/-
      0.7 to 7.4 +/- 1.9 mm2 (P < 0.01), whereas the plaque-thrombus area decreased
      significantly (13.8 +/- 1.7 mm2 before and 9.0 +/- 1.9 mm2 after PTCA; P < 0.01).
      The total vessel area remained virtually constant (15.9 +/- 1.9 mm2 before and
      16.4 +/- 2.5 mm2 after PTCA, NS). PTCA-induced plaque rupture or dissection was
      observed in only 13 (16.5%) patients. CONCLUSION: Intracoronary ultrasound
      imaging can be performed safely and successfully prior and subsequent to PTCA in
      selected patients with acute myocardial infarction. Early reperfusion via PTCA
      seems to be attributable to a significant reduction in the amount of low
      echogenic plaque and thrombus material, whereas factors like balloon-induced
      dissection and stretching of vessels play only a minor role.

PMID- 9285180
TI  - Coronary collateral blood-flow velocity improves with repeated coronary
      occlusions during angioplasty in patients with coronary artery disease and
      systemic hypertension.
AB  - BACKGROUND: Cardiac hypertrophy is associated with numerous alterations in the
      coronary circulation. OBJECTIVE: To test the hypothesis that, during angioplasty,
      the coronary collateral blood flow during repetitive coronary occlusions
      increases more in hypertensives than it does in normotensives. METHODS: We
      studied 34 patients (22 normotensives and 12 hypertensives) with stable angina
      and single-vessel disease undergoing coronary angioplasty during two similar
      balloon inflations. Each balloon inflation was maintained for 120 s. The coronary
      blood flow velocity was estimated using the Doppler-flow guide wire, which was
      positioned distally to the lesion. Flow velocities were recorded before balloon
      deflation. RESULTS: The average peak velocity increased by 29.0 +/- 14.7 mm/s in
      the hypertensives and decreased by 9.4 +/- 4.9 mm/s in the normotensives (P <
      0.01) during the second balloon inflation, whereas the velocity-time integral
      increased by 33.1 +/- 19.2 mm and decreased by 14.3 +/- 11.3 mm (P < 0.05),
      respectively. The ST-segment elevation decreased by 1.13 +/- 1.27 and by 0.17 +/-
      0.16 mV, respectively (P = 0.01). The increase in the average peak velocity which
      occurred during the second balloon inflation was related to the left ventricular
      mass (r = 0.47, P = 0.004). CONCLUSION: These results indicate that the coronary
      collateral blood flow velocity improves with repetitive coronary occlusions
      during angioplasty in patients with systemic hypertension and that this increase
      is correlated to the left ventricular mass.

PMID- 9285182
TI  - A randomized animal study evaluating the efficacies of locally delivered heparin
      and urokinase for reducing in-stent restenosis.
AB  - BACKGROUND: In-stent restenosis is primarily due to neointimal hyperplasia.
      Results from recent nonrandomized studies suggest that local delivery of heparin
      or urokinase to the site of angioplasty or stenting results in a lower rate of
      restenosis. OBJECTIVE: To determine whether local delivery of heparin or
      urokinase reduces in-stent restenosis. METHODS AND RESULTS: Thirty-three pigs
      were assigned randomly to one of three groups: controls (n = 9) administered
      local saline infusion, the heparin group (n = 15) administered local heparin
      (6000 u/10 min), and the urokinase group (n = 9) administered local urokinase
      (250000 u/10 min), via a local delivery catheter (Dispatch) at the site of
      subsequent stent implantation. Prior to local delivery, all of the animals were
      subjected to balloon injury (balloon:artery diameter ratio approximately or =
      1.3) to facilitate intramural drug impregnation. After local therapy, one Palmaz
      Schatz stent (mean stent: artery diameter ratio approximately or = 1.25) was
      implanted within the left anterior descending coronary artery. The degree of
      neointimal hyperplasia was evaluated 4 weeks later by angiography (as the maximal
      percentage diameter stenosis) and histology (as the maximal neointimal area
      stenosis). We found no difference in percentage diameter stenosis (46 +/- 18%
      control, 42 +/- 27% heparin group, and 37 +/- 20% urokinase group, P = 0.7) and
      corrected neointimal area (1.06 +/- 0.42 mm2 control, 0.94 +/- 0.29 mm2 heparin,
      and 0.88 +/- 0.26 mm2 urokinase group, P = 0.7) among groups at follow-up. The
      activated clotting time rose slightly for heparin-treated animals, suggesting
      that systemic delivery had occurred, whereas fibrinogen levels did not change in
      urokinase-treated animals. CONCLUSIONS: Local deliveries of heparin and urokinase
      via the Dispatch catheter, at the chosen dosages, do not reduce in-stent
      neointimal hyperplasia in this porcine model.

PMID- 9285181
TI  - Does long-term angiotensin converting enzyme inhibition affect the concentration
      of tissue-type plasminogen activator-plasminogen activator inhibitor-1 in the
      blood of patients with a previous myocardial infarction.
AB  - BACKGROUND: Large-scale studies have indicated that treatment with angiotensin
      converting enzyme (ACE) inhibitors reduces the incidence of myocardial infarction
      and unstable angina pectoris among patients with recent myocardial infarction and
      moderate left ventricular dysfunction. An improved endogenous fibrinolysis might
      be responsible for this effect. OBJECTIVES: To investigate the effect of
      trandolapril on the endogenous tissue-type plasminogen activator (t-PA) in
      patients with a recent myocardial infarction and moderate left ventricular
      dysfunction. METHODS: Fifty-six patients with acute myocardial infarction and a
      wall motion index < or = 1.2 were allocated randomly either to administration of
      trandolapril or to placebo. When possible, the study drug dose was increased
      gradually to 4 mg trandolapril or a corresponding amount of placebo during the
      first month after randomization. Blood samples for determination of the variables
      of the fibrinolytic system, ACE activity and ACE genotype were collected prior to
      randomization and during out-patient visits in months 1, 3, 6, 9 and 12. After
      the subject had fasted overnight, blood samples were collected in the morning
      (0800-1000 h) after the subject had rested supine for at least 15 min, from a
      venous cannula inserted into the forearm. The effect of trandolapril on the
      fibrinolytic variables was evaluated by calculating the area under the curve
      (AUC1-12) from month 1 to month 12. RESULTS: The trandolapril group and the
      placebo group were similar with respect to baseline clinical characteristics,
      baseline fibrinolytic variables and baseline plasma ACE activity. The
      trandolapril group did not differ significantly from the placebo group with
      respect to AUC1-12 t-PA antigen [11.67 (3.95-26.45) versus 10.34 ng/ml (3.71
      19.62), P = 0.19] and AUC1-12 plasminogen activator inhibitor type-1 (PAI-1)
      antigen [27.57 (8.38-89.49) versus 24.40 ng/ml (7.94-90.62), P = 0.92]. A
      significant and clear trend in variation with time of t-PA antigen was observed
      for the trandolapril group, but not for the placebo group. The fibrinolytic
      variables were similar at baseline for the different ACE genotype insertion (I)
      and deletion (D) groups (II, ID and DD). Trandolapril treatment was associated
      with a significant (P < 0.04) increase in the AUC1-12 of t-PA antigen in the ID
      group compared with that of the placebo-treated ID group, whereas PAI-1 antigen
      concentration did not differ between the groups. Trandolapril treatment was not
      associated with any significant change in the fibrinolytic variables for the
      other genotype groups. CONCLUSIONS: Chronic ACE-inhibitor treatment with
      trandolapril was not associated with any significant difference in the blood
      concentrations of t-PA and PAI-1 compared with placebo. The suggested specific
      interaction between ACE inhibition and the increase in t-PA in patients with ACE
      genotype ID will require further confirmation.

PMID- 9285183
TI  - The effect of basic fibroblast growth factor on coronary vascular tone in
      experimental hypercholesterolemia in vivo and in vitro.
AB  - OBJECTIVE: To determine whether bFGF causes coronary vasoconstriction in
      experimental hypercholesterolemia in association with endothelial dysfunction.
      METHODS: We infused 0.02 microgram/kg per min bFGF into the left anterior
      descending artery of anesthetized pigs (n = 5) before and after 10 weeks of a
      high-cholesterol diet. The coronary artery diameter (CAD) was measured by
      quantitative angiography and the coronary blood flow (CBF) was calculated using
      coronary-flow Doppler measurements. In additional in-vitro studies, epicardial
      arteries from normal and hypercholesterolemic pigs were exposed to cumulative
      concentrations of bradykinin (10(-11)-10(-6) mol/l) after precontraction with 10(
      6) mol/l endothelin-1. Cumulative concentrations of bFGF (10(-13)-10(-8) mol/l)
      were added to other vessels with and without prior contraction with 10(-5) mol/l
      PGF2 alpha. Similar in-vitro studies were performed using rings from which the
      endothelium had been removed. RESULTS: In vivo, intracoronary administration of
      bFGF increased the CBF by 33 +/- 33% and the CAD by 12 +/- 5% at baseline, but
      reduced the CBF by 45 +/- 8% and the CAD by 14 +/- 6% after 10 weeks of a high
      cholesterol diet. In vitro, the endothelium-dependent vasorelaxation in response
      to bradykinin was attenuated significantly in coronary arteries from
      hypercholesterolemic pigs (P < 0.05). Cumulative concentrations of bFGF exerted
      no effect on the coronary epicardial tone both in normal (with and without
      endothelium) and in hypercholesterolemic pigs. CONCLUSIONS: Acute administration
      of intracoronary bFGF caused coronary vasodilatation under steady-state
      conditions and vasoconstriction under diet-induced hypercholesterolemia. In
      vitro, bFGF did not affect the coronary epicardial tone. These findings suggest
      that the coronary vasoactive properties of bFGF may be exerted indirectly and are
      affected by the functional integrity of the endothelium.

PMID- 9285185
TI  - Bibliography current world literature.

PMID- 9285184
TI  - Cytomegalovirus in transplantation: new developments.
AB  - The control of cytomegalovirus infection and disease continues to be a major
      problem in transplantation and different strategies have been developed to reduce
      its incidence. Early diagnosis of infection soon after transplantation, using
      molecular tools such as the polymerase chain reaction, have resulted in
      successful clinical trials using the strategy of pre-emptive therapy. Adoptive
      transfer of immune cells, which are predominantly the cytomegalovirus-specific
      cytotoxic T lymphocytes, into transplant recipients has been shown to restore
      effective immunity. A vaccine preparation has been in development aimed at
      preventing primary infections in allograft recipients though effective protection
      has yet to be shown. The mechanisms of viral pathogenesis in chronic graft
      rejection remain unclear; however, recent contributions from the field of cell
      biology have increased our understanding of possible processes which have the
      potential for application in the field of gene therapy for the treatment of
      disease.

PMID- 9285186
TI  - Renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) is characterized by (a) lack of early warning signs,
      which results in a high proportion of patients with metastases at the time of
      diagnosis; (b) protean clinical manifestations; and (c) resistance to
      radiotherapy and chemotherapy. The estimates of new diagnoses and deaths from
      kidney cancer in the United States during 1996 are 30,600 and 12,000,
      respectively. RCC occurs nearly twice as often in men as in women. The age at
      diagnosis is generally older than 40 years; the median age is in the midsixties.
      The incidence of RCC has been rising steadily. Between 1974 and 1990, there was a
      38% increase in the number of patients who had a diagnosis of RCC. This increase
      was accompanied by a significant improvement in 5-year survival. Both trends are
      likely the result of improved diagnostic capability. Newer radiographic
      techniques, including ultrasonography, computed tomography, and magnetic
      resonance imaging, are detecting kidney tumors more frequently and at a lower
      disease stage, when tumors can be resected for cure. Surgical treatment is the
      only curative therapy for localized RCC. Radical nephrectomy remains the mainstay
      of surgical management, but techniques are being modified. These modifications
      include partial nephrectomy and resection of vena caval thrombi. In highly
      selected cases, surgical resection of locally recurrent RCC or of disease at a
      solitary metastatic site is associated with long-term survival. Metastatic RCC is
      highly resistant to the many systemic therapies that have been extensively
      investigated. A minority of patients achieve complete or partial response to
      interferon, interleukin-2, or both. Response can be dramatic but is rarely
      durable. Because most patients do not achieve response, these agents are not
      considered effective treatments for RCC, but the response in some patients
      indicates the need for continued research on their use. Identification of new
      agents with better antitumor activity against metastases remains a high priority
      in clinical investigation of therapy for this refractory disease.

PMID- 9285187
TI  - Spindle-cell lesions of the mediastinum: diagnosis by fine-needle aspiration
      biopsy.
AB  - Spindle cells seen in fine-needle aspiration biopsy (FNAB) of the mediastinal
      lesions can be a component of a wide variety of benign and malignant conditions.
      Few of these conditions, however, are described in the FNA cytopathology
      literature. This review discusses the cytopathologic features, differential
      diagnoses, and potential pitfalls of a variety of lesions with a significant
      component of spindle cells encountered in mediastinal FNAB. The cytopathology
      files from four institutions were searched for cases of mediastinal FNAB
      containing a spindle-cell component that was a key or predominant cytologic
      feature of the diagnostic specimen. The cytomorphologic features of these cases
      were analyzed, and their differential features are discussed. Of 196 mediastinal
      FNABs, 22 (11%) were lesions with significant spindle-cell component:
      granulomatous inflammation (four); benign nerve sheath tumor (four); thymic cyst
      (two); spindle-cell thymoma (two); large-cell non-Hodgkin's lymphoma with
      sclerosis (two); nodular sclerosing Hodgkin's disease (two); liposarcoma (two);
      spindle-cell squamous carcinoma possibly arising in a teratoma (one); unspecified
      high-grade sarcoma (one); spindle-cell malignant melanoma (one); and nonspecific
      fibrous tissue (one). The cytologic features of each lesion were analyzed as an
      aid for accurate classification. These findings were correlated with radiologic
      and clinical information when available. The value of ancillary studies performed
      on aspirated material in selected cases was also reviewed. FNA of mediastinal
      lesions with significant spindle-cell morphology represents an infrequent and
      heterogeneous group of entities that may pose significant diagnostic challenges.
      This review presents the salient cytopathologic features of various spindle-cell
      lesions of the mediastinum with particular emphasis on differential diagnosis and
      pitfalls. The pathologist must use caution when interpreting these lesions and
      ancillary studies may be of significant value in selected cases.

PMID- 9285188
TI  - Needle aspiration cytology of pancreatic cystic lesions.
AB  - Forty-two histologically confirmed cases of pancreatic cystic lesions with
      cytologic evaluation by needle aspiration biopsy (NAB) were reviewed. There were
      21 inflammatory pseudocysts (IPC), nine mucinous cystic neoplasms (MCN), six
      microcystic serous adenomas (MSA), one macrocystic serous adenoma, and five
      papillary solid and cystic neoplasms (PSCN). Correct cytodiagnosis was made in
      all cases of IPC and MCN. The contents of IPCs were characterized by turbid or
      blood-tinged fluid containing cellular debris, numerous foamy macrophages, and
      other inflammatory cells. There were few or no epithelial lining cells. The
      aspirates from MCNs showed gelatinous mucoid material containing mucus-secreting
      cells that were present singly, in clusters, or in sheets. Depending on the
      individual case, benign or malignant columnar cells, or an admixture of these
      cells, were present in a mucinous background. The preoperative needle aspirates
      of five MSAs were acellular. In one case of MSA and in one example of macrocystic
      serous adenoma, small monolayered sheets of benign cubic epithelial cells were
      seen in the needle aspirates. Similar cytologic findings were noted in the
      materials obtained by intraoperative NAB performed under direct vision of the
      aforementioned five MSAs. Difficulties were encountered in typing three PSCNs
      that yielded in NAB cells resembling those of an islet cell tumor. They were
      diagnosed as low-grade neoplasms (PSCN vs. islet cell tumor). In two other
      patients, a cytodiagnosis of PSCN was correctly made as the NAB revealed
      monomorphic tumor cells wrapping around small capillary blood vessels.

PMID- 9285189
TI  - Salivary gland lesions with a prominent lymphoid component: cytologic findings
      and differential diagnosis by fine-needle aspiration biopsy.
AB  - Fine-needle aspiration (FNA) is an accepted technique for the preoperative
      diagnosis of salivary gland nodules. The majority of salivary gland nodules are
      pleomorphic adenomas and offer little difficulty in diagnosis. Most
      diagnostically difficult lesions fall into one of four morphologic categories
      represented by squamous-cell-containing lesions, clear cell neoplasms, neoplasms
      with a prominence of stromal material, and lymphocyte-containing lesions. Herein,
      we describe our experience with a series of 61 histologically confirmed cases in
      which the smears contained a prominent or predominant number of lymphocytes. The
      differential diagnosis is discussed and points of diagnostic aid enumerated.

PMID- 9285191
TI  - Cytodiagnosis of pure primary squamous-cell carcinoma of the breast by fine
      needle aspiration cytology.
AB  - In this communication five cases of pure primary squamous-cell carcinoma of the
      breast are presented in which the diagnosis was made by fine-needle aspiration
      cytology. All patients were women. The aspiration cytodiagnosis was further
      confirmed by subsequent examination of cell blocks from the aspirated material
      and biopsy of the breast mass. The cytohistologic features in all cases were
      characterized by numerous malignant squamous cells with keratinizing cytoplasm,
      hyperchromatic dense nuclei, coarse chromatin, thickened nuclear membranes,
      keratin debris, and background necrosis. The identification of malignant squamous
      cells as predominant cells in aspirate samples from the breast is quite important
      and should be followed by a search for other sources of a primary tumor before a
      diagnosis of pure primary squamous-cell carcinoma of the breast is accepted. The
      value of immunocytochemical study despite immunopositivity for cytokeratin and
      epithelial membrane antigen (EMA) and immunonegativity for carcinoembryonic
      antigen (CEA) and B72.3 was considered to be somewhat uncertain.

PMID- 9285190
TI  - Breast care consultation center: role of the pathologist in a multidisciplinary
      center.
AB  - The Breast Care Consultation Center (BCCC) is a multidisciplinary center
      providing, in a single setting, a complete outpatient facility for women who have
      been diagnosed with or suspected of having breast cancer. A team of specialists
      are available to provide comprehensive, diagnostic (radiologist, surgeon, and
      pathologist), therapeutic (surgeon, radiotherapist, and medical oncologist), and
      support options. The pathologist, as a member of the diagnostic team, evaluates
      the material obtained or received at the BCCC. These include fine-needle
      aspirations (FNAs) obtained on-site as well as previously prepared
      cytohistological specimens. The pathologist renders the diagnosis following
      examination of the material and consultation with the multidisciplinary team.
      Thus, this approach is conducive for appropriate and accurate diagnosis where all
      data are available. In addition, the pathologist discusses the findings of each
      patient in the multidisciplinary conference. One thousand four hundred eighteen
      patients were evaluated at Magee-Womens Hospital BCCC from February 1992 through
      December 1994, during which time 366 FNAs were performed. The accuracy for
      positive diagnosis was 100%. Six negative cases had cancer on histology; these
      were due to sampling error (the lesion was missed). A multidisciplinary team is
      ideal for the evaluation of breast lesions that are suspicious for malignancy as
      it provides one-stop shopping and same-day diagnosis and therapeutic decisions.

PMID- 9285192
TI  - Fine-needle aspiration of epithelioid malignant peripheral nerve sheath tumor
      (epithelioid malignant schwannoma).
AB  - The epithelioid variant of malignant peripheral nerve sheath tumor (MPNST), also
      known as malignant epithelioid schwannoma, is a relatively rare and recently
      characterized clinicopathologic entity. The epithelioid variant of MPNST shares
      many clinical features with conventional MPNST but is characterized by different
      histologic and cytologic features. These include a distinctive nesting pattern
      and an abundance of cytoplasm not seen in histology of conventional nerve sheath
      tumors. Cytologically, the epitheliod variant shows a propensity to cellular
      discohesiveness and a plasmacytoid or epitheliod appearance that is in
      contradistinction to the spindled appearance of the usual MPNST. Herein, we
      report our experience with fine-needle aspiration (FNA) of two epithelioid
      malignant schwannomas and discuss the FNA cytologic differential diagnosis.

PMID- 9285193
TI  - Olfactory neuroblastoma (esthesioneuroblastoma): appearance on fine-needle
      aspiration: report of a case.
AB  - Small round-cell tumors can arise from several anatomic sites in children and
      adults, and their primary diagnosis and clinical course often present challenges
      to physicians. We present a case of a rare adult-onset round-cell tumor,
      esthesioneuroblastoma, of nasal epithelial origin, which spread into the brain
      and subsequently to cervical lymph nodes. The report describes how fine-needle
      aspiration cytology identified the metastatic spread and contributed to its
      clinical management. The use of ancillary procedures in differential diagnosis of
      small round-cell tumors is reviewed.

PMID- 9285194
TI  - Taxol effect: bizarre mitotic figures (abnormal spindle asters) in a malignant
      peritoneal effusion: report of a case.
AB  - Taxol (Paclitaxol) is a diterpenoid taxane derivative found in the bark and
      needles of the Western yew, Taxus brevifolia, indigenous to the old growth
      forests of the Pacific Northwest. As compared with other antineoplastic agents
      (vinca alkaloids and colchicine) that enhance microtubule disassembly, taxol
      promotes microtubule polymerization. In interphase cells, abnormal microtubular
      bundles or arrays are seen. In mitotic cells, abnormal spindle asters form. Such
      morphologic changes have been described frequently in cell culture systems and in
      in vitro systems using fresh tumor tissue. To our knowledge, these changes have
      not been described in a peritoneal effusion specimen from a patient with stage
      III ovarian cancer treated with taxol. In addition, the mitotic stabilization
      produced interpretative difficulties in evaluating the peritoneal fluid because a
      vast majority of the presumed malignant cells were in mitosis and, hence, not
      evaluable by ordinary cytologic criteria.

PMID- 9285195
TI  - Fine-needle aspiration cytodiagnosis of Liesegang rings in women presenting with
      a mammographic opacity.
AB  - In this communication three women patients are described in which fine needle
      aspiration cytology was undertaken as a first line of noninvasive investigation
      to determine the cause of a mammographic opacity. The cytologic findings in the
      three cases showed features of apocrine cysts with numerous spherical ring-like
      structures resembling Liesegang rings of various sizes, with double-layer outer
      wall, striations, and an amorphous central nidus. Although similar structures
      have been described by us very rarely in breast cysts, their presence in a
      mammographic opacity was noted for the first time. Furthermore, in the three
      cases fine-needle aspiration cytology not only resulted in a specific diagnosis
      but also obviated the need for any invasive surgery apart from relieving patient
      anxiety and clinical concern by excluding a serious lesion.

PMID- 9285196
TI  - Interdigitating reticulum-cell sarcoma of the intestine: a case report and review
      of the literature.
AB  - Dendritic cells are immune accessory cells which are widely distributed in many
      tissues. Those which are present within lymphoid follicle centers are classified
      as follicular dendritic cells. Those which are found outside germinal centers may
      be referred to as interdigitating reticulum cells, or Langerhans cells when they
      occur in the skin. Abnormal proliferations of dendritic cells are best known as
      the group of disorders comprising Langerhans-cell histiocytosis, which occurs
      primarily in children and teenagers. There are increasing reports of malignant
      proliferations of both types of dendritic cells in adults. However, there is only
      one previous description of the cytologic features of a dendritic cell sarcoma
      based on imprint cytology of a resected jejunal mass. The current report provides
      a detailed description of the cytologic features of a fine-needle aspirate of a
      recurrence of an interdigitating reticulum-cell sarcoma of the cecum.

PMID- 9285197
TI  - Intramammary lymph nodes: cytologic findings and implications for fine-needle
      aspiration cytology diagnosis of breast nodules.
AB  - The recognition of intramammary lymphoid proliferations is important because
      smears of these proliferations would be judged as insufficient by several of the
      published criteria for specimen adequacy. Alternatively, some might be confused
      with medullary carcinoma of the breast or adenocarcinomas with a "single-cell"
      pattern. We found 19 intramammary lymphoid proliferations in a series of 887 fine
      needle aspirates of palpable breast nodules. Six were lymphomas and 13 were
      benign intramammary lymph nodes. Smear cellularity ranged from scant to high, but
      in all cases, lymphocytes dominated the cell population. The cytology of
      intramammary lymph nodes and lymphoma did not differ from those occurring at
      other sites.

PMID- 9285198
TI  - Sources of diagnostic error in the fine-needle aspiration diagnosis of Warthin's
      tumor and clues to a correct diagnosis.
AB  - Squamous metaplasia and cystic degeneration in Warthin's tumor (WT) are not
      uncommon. A recent case of WT misdiagnosed as metastatic squamous carcinoma with
      cystic change prompted us to review our experience with fine-needle aspiration
      (FNA) of WT, with special attention given to potential sources of diagnostic
      pitfalls. Aspirations from 16 cases of histologically confirmed WT were
      retrospectively evaluated for cellularity, cell composition, and background. The
      FNA review diagnosis was compared with the previous FNA and corresponding tissue
      findings. All tumors presented in the parotid gland. The initial cytologic
      diagnoses were: WT in 13 cases, oncocytoma vs. low-grade mucoepidermoid carcinoma
      in 1, squamous carcinoma vs. branchial cleft cyst in 1, and squamous carcinoma in
      1. On review, 13 cases (81%) showed typical features associated with WT: Moderate
      to abundant oncocytic epithelium, lymphoid stroma, background debris, and mild
      squamous metaplasia. In the remaining cases, one lacked a lymphoid stroma and
      could not be further classified (initially called "oncocytoma vs. low-grade
      mucoepidermoid carcinoma"). The other 2 cases contained moderate to abundant
      atypical squamous cells and extensive necrotic/mucoid debris, and review
      diagnoses were consistent with the initial cytologic diagnoses (squamous
      carcinoma in one, and branchial cleft cyst vs. squamous carcinoma in the other).
      In our series, typical features of WT were seen in 81% of cases. Atypical
      features are largely present as individual metaplastic squamous cells. Diagnostic
      errors are caused by a lack of typical features and the presence of individual
      atypical squamous cells in a necrotic background mimicking carcinoma. An
      awareness of the morphologic variation present on cytologic preparations and
      correlation with clinical findings should prevent erroneous interpretation in the
      FNA setting.

PMID- 9285199
TI  - Preliminary risk-benefit assessment of mycophenolate mofetil in transplant
      rejection.
AB  - Mycophenolate mofetil (the morpholinoethyl ester of mycophenolic acid) inhibits
      de novo purine synthesis via the inhibition of inosine monophosphate
      dehydrogenase. Its selective lymphocyte antiproliferative effects involve both T
      and B cells, preventing antibody formation. Mycophenolate mofetil has immuno
      suppressive effects alone, but is used most commonly in combination with other
      immunosuppressants. Mycophenolate mofetil, in combination with cyclosporin and
      corticosteroids, has been studied in large, randomised clinical trials involving
      nearly 1500 renal allograft transplant recipients. These trials demonstrated that
      mycophenolate mofetil is significantly more effective in reducing treatment
      failure and acute rejection episodes than placebo or azathioprine. Additionally,
      mycophenolate mofetil may be able to reduce the occurrence of chronic rejection.
      Mycophenolate mofetil is relatively well tolerated. The most common adverse
      effect reported is gastrointestinal intolerance; haematological aberrations have
      also been noted. The reversible cytostatic action of mycophenolate mofetil allows
      for dose adjustment or discontinuation, preventing serious toxicity or an overly
      suppressed immune system. Cytomegalovirus tissue invasive disease and the
      development of malignancies are concerns that merit evaluation in long term
      follow-up studies. Mycophenolate mofetil does not cause the adverse effects
      typically associated with other commercially available immunosuppressant
      medications such as nephrotoxicity, hepatotoxicity, hypertension, nervous system
      disturbances, electrolyte abnormalities, skin disorders, hyperglycaemia,
      hyperuricaemia, hypercholesterolaemia, lipid disorders and structural bone loss.
      Based on preliminary information, a positive benefit-risk ratio has been
      demonstrated with the use of mycophenolate mofetil in the prophylaxis of
      rejection in cadaveric renal allograft transplantation. Data from studies in
      other types of organ transplants are promising, but are too limited to draw clear
      conclusions. Long term follow-up studies are required to confirm these
      observations. Although mycophenolate mofetil is expensive, the beneficial effects
      on the reduction of rejection, treatment failure and related expenses suggest
      that it is most likely to be cost effective.

PMID- 9285200
TI  - Cytokine-induced autoimmune disorders.
AB  - Cytokines are now commonly used in the treatment of many conditions, especially
      cancer, haematological malignancies and chronic viral hepatitis. With some of
      these cytokines, clinical induction and/or exacerbation of autoimmune
      manifestations have been observed. This has been the case with interferon-alpha
      and interferon-gamma, interleukin-2 and some colony-stimulating factors. All
      known biological and clinical autoimmune features have been observed but thyroid
      abnormalities have been particularly frequent. Some of these manifestations
      appear to be related to the effect of these exogenous cytokines on the T helper
      cell (TH) 1/TH2-cytokine balance and the regulatory properties of these cells.
      Patients with a history of underlying autoimmune disease or baseline serological
      abnormalities should be monitored for autoimmunity when treated with certain TH1
      or TH2-inducing cytokines.

PMID- 9285202
TI  - Role of desensitisation for drug hypersensitivity in patients with HIV infection.
AB  - Drug hypersensitivity is common in patients with HIV infection and manifests as a
      delayed onset maculopapular rash, often with fever, mucositis and occasionally
      visceral involvement. In the 50% of patients who require treatment modification,
      many can be treated with an equally effective alternative that does not cause
      hypersensitivity. For the remainder, options include 'treating through' the
      reaction, adjunctive corticosteroids and/or antihistamines, rechallenge and
      desensitisation. Formal comparisons are lacking but preliminary data suggest that
      desensitisation is more successful than rechallenge. The most common reason for
      performing desensitisation is sulphonamide hypersensitivity for treatment or
      prophylaxis of pneumocystosis, where success rates of 68 to 100% have been
      reported. Success seems more likely when regimens lasting 7 or more days are used
      and in patients with lower CD4+ lymphocyte counts. However, the best tolerated,
      effective and simple desensitisation regimen has not been determined.

PMID- 9285201
TI  - Drug-induced orthostatic hypotension in the elderly: avoiding its onset.
AB  - The prevalence of orthostatic hypotension in the elderly is reported to be 5 to
      33%. This high prevalence contributes to the risk of syncope and falls in old
      age. Drugs are a major cause of postural hypotension. Changes in pharmacokinetics
      and pharmacodynamics occur with aging in relation to many drugs, resulting in
      delayed elimination and increased bioavailability. Therefore, drugs with an
      antihypertensive action (diuretics, calcium antagonists, beta-blockers, ACE
      inhibitors, alpha 1-blockers, and centrally acting antihypertensives) have a more
      pronounced effect in the elderly. Nitrates, antiparkinsonian drugs,
      antidepressants and antipsychotics all cause hypotension as a known adverse
      effect. When assessing orthostatic hypotension in the elderly, drug treatment
      should always be reviewed. Whenever possible, antihypertensive drugs should be
      discontinued, and the dosages of essential drugs should be reduced.

PMID- 9285205
TI  - Thyrotropin (TSH) beta-subunit gene expression--an example for the complex
      regulation of pituitary hormone genes.
AB  - Synthesis of pituitary hormones was shown to be efficiently regulated at the
      transcriptional level. The specialized function of the five cell types in the
      anterior pituitary is controlled by ubiquitous as well as cell-specific
      transcription factors. Pit-1 is such a cell-specific regulator found only in
      lacto-, somato- and thyrotropes which could be shown to be essential for basal
      expression of growth hormone (GH) and prolactin (Prl) genes and the regulated
      expression of Prl and thyrotropin (TSH) beta-subunit genes. Identification of
      distinct binding sites for transcription factors and some of the mechanisms of
      transcriptional control shed light on the complex regulation of pituitary hormone
      gene expression which is exemplified for the TSH beta gene. The control of basal
      as well as positively and negatively regulated expression of some pituitary
      hormone genes becomes fairly well understood by the investigation of the role of
      Pit-1. Identification of different mutations in the human pit-1 gene supported
      the role of this protein for combined pituitary hormone deficiency (CPHD)
      characterized by the deficiency of GH, prolactin and TSH.

PMID- 9285204
TI  - Glucagon-like peptide 1 (GLP-1) as a new therapeutic approach for type 2
      diabetes.
AB  - Glucagon-like peptide 1 (GLP-1) is a physiological incretin hormone in normal
      humans explaining in part the augmented insulin response after oral versus
      intravenous glucose administration. In addition, GLP-1 also lowers glucagon
      concentrations, slows gastric emptying, stimulates (pro)insulin biosynthesis,
      reduces food intake upon intracerebroventricular administration in animals, and
      may, in addition, enhance insulin sensitivity. Therefore, GLP-1, in many aspects,
      opposes the Type 2-diabetic phenotype characterized by disturbed glucose-induced
      insulin secretory capacity, hyperglucagonaemia, moderate insulin deficiency,
      accelerated gastric emptying, overeating (obesity) and insulin resistance. The
      other incretin hormone, gastric inhibitory polypeptide (GIP), has lost almost all
      its activity in Type 2-diabetic patients. In contrast, GLP-1 glucose-dependently
      stimulates insulin secretion in diet- and sulfonylurea-treated Type 2-diabetic
      patients and also in patients under insulin therapy long after sulfonylurea
      secondary failure. Exogenous administration of GLP-1 ([7-37] or [7-36 amide]) in
      doses elevating plasma concentrations to approximately 3-4 fold physiological
      postprandial levels fully normalizes fasting hyperglycaemia in Type 2-diabetic
      patients. The half life of GLP-1 is too short to maintain therapeutic plasma
      levels for sufficient periods by subcutaneous injections. Current research
      activities aim at finding GLP-1 analogues with more suitable pharmacokinetic
      properties than the original peptide. Another approach could be the augmentation
      of endogenous release of GLP-1, which is abundant in L cells of the lower small
      intestine and the colon. Interference with sucrose digestion using alpha
      glucosidase inhibition moves nutrients into distal parts of the gastrointestinal
      tract and, thereby, prolongs and augments GLP-1 release. Enprostil, a
      prostaglandin E2 analogue, fully suppresses GIP responses, while only marginally
      affecting insulin secretion and glucose tolerance after oral glucose, suggesting
      compensatory hypersecretion of additional insulinotropic peptides, possibly
      including GLP-1. Given the large amount of GLP-1 present in L cells, it appears
      worthwhile to look for more agents that could 'mobilize' this endogenous pool of
      the 'antidiabetogenic' gut hormone GLP-1.

PMID- 9285203
TI  - A guide to the safety of CNS-active agents during breastfeeding.
AB  - For most agents with CNS activity, there are limited data regarding their safety
      in breastfeeding. Any decision to institute treatment for a neurological or
      psychiatric disorder must weigh the benefits of maternal treatment against the
      potential harm to the breastfeeding mother of withholding medication which may
      improve her illness. For the neonate, one must balance the risk of medication
      exposure against the benefit of receiving breast milk. Most tricyclic
      antidepressants can be used in lactating women. Because of the limited data,
      selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors should only
      be used with due consideration of the potential adverse effects. Breastfeeding is
      best avoided by women who require lithium therapy, because of both the immature
      excretory systems in the infant and relatively high doses received by the infant.
      There is little information about the safety of antipsychotic medications in
      breastfeeding. Concerns include toxicity and abnormal neurological development in
      the infant. These agents may be used with caution. Most agents which cause
      depression of the CNS, including opiates and sedatives, can be used in small
      doses and for short courses in breastfeeding mothers. Most anticonvulsants can be
      used in lactating women. Reference texts and consultation with experts are useful
      adjuncts to discussion of the risks and benefits of therapy with the patient. The
      scope of this review is limited to drugs with therapeutic uses, thus drugs of
      abuse are not discussed, nor are caffeine and alcohol (ethanol).

PMID- 9285206
TI  - Activated haemostasis in diabetic vascular complications: a role for tissue
      factor?

PMID- 9285207
TI  - Tissue factor antigen is elevated in patients with microvascular complications of
      diabetes mellitus.
AB  - Patients with late diabetic complications have increased levels of parameters
      indicating activation of coagulation (Takakashi et al., 1989; Ceriello, 1993;
      Murakami et al., 1993; Kario et al., 1995; Shimizu et al., 1995; Yokoyama et al.,
      1996), endothelial cell damage (Jensen, 1989; Iwashima et al., 1990; Sernau et
      al., 1995; Gabath et al., 1996). TF is believed to activate the coagulation
      mechanism in patients with late complications of diabetes. We studied the TF
      antigen plasma levels in 72 patients with diabetes mellitus (36 type I, 36 type
      II) with respect to its relevance as a marker of microvascular diabetic
      complications. TF levels did not correlate with macrovascular disease, diabetes
      type or age. Sixty patients with decreased renal function not due to diabetes
      were studied for evaluation of the contribution of renal failure to TF antigen
      plasma levels. We did not find a significant correlation of TF with s-creatinine
      in non diabetic patients (r = 0.27, p > 0.05). However, TF levels were elevated
      in diabetic patients with microvascular disease. Patients with retinopathy had
      higher TF levels than without (0.30 ng/ml vs 0.11 ng/ml, p < 0.007). When
      patients were divided into subgroups according to the urine albumin
      concentration, TF antigen of patients without albuminuria (0.019 ng/ml, n = 25)
      did not differ from patients with microalbuminuria (0.095 ng/ml, n = 19 p >
      0.05). However, TF levels were significantly higher in patients with
      macroalbuminuria (n = 28; 0.215 ng/ml, p < 0.005). Thus activation of coagulation
      in patients with microvascular complications of diabetes may be triggered by
      tissue factor.

PMID- 9285208
TI  - Total plasma antioxidants in first-degree relatives of patients with insulin
      dependent diabetes.
AB  - Insulin-dependent diabetes mellitus (IDDM) is a chronic disorder that results
      from autoimmune destruction of the pancreatic beta-cells. Recent evidence
      suggests that oxidative damage, resulting from both cytokine-induced production
      of toxic free radicals and low antioxidant capacity of the beta-cell plays a
      significant role in the pathogenesis of IDDM. Islet cell antibodies (ICA) have
      been the best validated marker of risk for the development of IDDM in predisposed
      individuals, i.e. first-degree relatives of patients with IDDM. We investigated
      the total plasma antioxidant status (TAS) in both ICA-positive and ICA-negative
      first-degree relatives of patients with IDDM, to assess the level of overall
      protection against oxidative damage. TAS was significantly lowered in ICA
      positive when compared to both ICA-negative and healthy subjects (p < 0.001),
      while no significant difference was found in comparison to recently diagnosed
      patients with IDDM. TAS values were not significantly influenced by gender, age
      and smoking habits in all groups, as well as by ICA titers in the group of ICA
      positive subjects. Results indicate that prediabetic condition, apart from well
      established immunological and metabolic alterations, could be associated with
      biochemical changes revealing complex disturbances of the antioxidative defence
      system. Although TAS is a functional rather than specific marker, its measurement
      is likely to be a valuable tool for understanding the mechanisms of specific beta
      cell injury.

PMID- 9285209
TI  - A time course study on the "in vitro" effects of T3 and testosterone on androgen
      and estrogen receptors in peripuberal primary rat Sertoli cells.
AB  - The effect of Tri-iodothyronine (T3) administration leading to the precocius
      differentiation of Sertoli cell in prepuberal rats has been previously shown. The
      functional maturation of Sertoli cells is associated with changes in androgen
      metabolism. We have recently demonstrated that T3 influences androgen metabolism
      in Sertoli cells by inhibiting aromatase activity and reduces drastically the ER
      contents in peripubertal hypothyroid rats. To better understand the role of T3 in
      modulating steroid action on Sertoli cells, we performed a time course study
      evaluating the in vitro effects of T3 and testosterone (T) on androgen (ARs) and
      estrogen (ERs) receptor content in Sertoli cells isolated from two weeks old
      Wistar rats. ARs and ERs basal levels did not change during the time course study
      indicating that the exposure to culture medium per se did not affect either
      receptor type. After 24 hrs of incubation with either T3 or T, a decrease of ERs
      in both nucleus and cytosol was observed. Such a decrease was augmented by the
      simultaneous administration of both hormones. ARs displayed a different temporal
      pattern in the two cellular compartments and exhibited an earlier rise in the
      cytosol induced by either T3 or T. At 36 hrs, ARs were significantly enhanced in
      both compartments in response to either T or T3 exposure while combined hormonal
      treatment caused an additive increase compared with the single treatment group.
      As a consequence of the opposite behaviour pattern displayed by ARs and ERs, the
      ratio between total ARs and ERs contents was increased after 24 hrs of exposure
      to hormonal treatment. To evaluate if treatments performed induced a functional
      maturation of Sertoli cells, transferrin levels in culture medium were measured.
      The increase of this protein paralleled that of ARs content as well as that of
      ARs/ERs ratio. This study demonstrates that thyroid hormone induces a progressive
      increase of (AR)/(ER) ratio in the differentiating Sertoli cells bringing them to
      a prevalent androgen dependency along their functional maturation.

PMID- 9285210
TI  - Polymorphism of the glucagon receptor gene and non-insulin-dependent diabetes
      mellitus in the Russian population.
AB  - Recently, a missense mutation in the glucagon receptor (GCG-R) gene causing a Gly
      to Ser change at codon 40 (Gly40Ser) has been associated and linked with non
      insulin-dependent diabetes mellitus (NIDDM). We screened 150 unrelated NIDDM
      patients and 109 non-diabetic subjects for the presence of the Gly40Ser
      polymorphism by use of polymerase chain reaction-restriction fragment length
      polymorphism in the Russian population. None of the NIDDM patients showed this
      polymorphism. In contrast, two of the control subjects were heterozygous carriers
      of the polymorphism. Both were healthy females without a family history of
      diabetes. The body mass index, age, and 2-h blood glucose levels of the two
      subjects with the polymorphism were similar to those of the control subjects
      homozygous for the wild-type. Our results suggest that Gly40Ser polymorphism of
      the GCG-R gene is not associated with NIDDM in the Russian population and point
      to the genetic heterogeneity of NIDDM in different ethnic groups.

PMID- 9285211
TI  - Atherosclerosis, aortic stenosis and sudden onset central diabetes insipidus.
AB  - The majority of cases of central diabetes insipidus are still pathogenetically
      unclear (idiopathic). Atherosclerotic cholesterol emboli might be partly
      responsible for some of these idiopathic cases. A 54-year-old woman with known
      aortic valve stenosis and a history of a transitory ischemic attack presented
      with sudden-onset polyuria and polydipsia of up to eight l/d, which had started
      acutely with headaches. She had been treated with lithium for 3 years because of
      cyclothymic depression. Plasma sodium was in the upper normal range (142-148
      mmol/l). Hypertonic saline infusion during lithium therapy revealed a normal
      threshold of thirst and resetting of vasopressin secretion (osmotic threshold >
      300 mosmol/l), whereas vasopressin reserve was normal. Lithium withdrawal led to
      an even greater delay of vasopressin release upon hypertonic saline infusion (>
      310 mosmol/l). Pituitary function tests revealed a normal anterior pituitary
      function. MR imaging of the hypothalamo-hypophyseal region showed a normal
      hypothalamic region and a highly intensive neurohypophyseal signal in the T1
      weighted image. The patient responded well to desmopressin. We suggest that in
      this rare case clinical symptoms as well as biochemical findings like impairment
      of AVP release might be related to a minor structural hypothalamic damage by a
      vascular lesion, caused, for example, by an atheromatous (cholesterol) embolism
      in the hypothalamic region responsible for integration of osmoreceptor function
      and AVP-secretion. The patient's atherosclerosis and aortic stenosis might be
      responsible for this event.

PMID- 9285212
TI  - Apoplexy of a pituitary macroadenoma as a severe complication of preoperative
      thyrotropin-releasing hormone (TRH) testing.
AB  - The case history of a 54-year-old male suffering from pituitary macroadenoma with
      suprasellar extension is reported. A TRH-test with 200 micrograms i.v. was
      followed by severe headache and vomiting after 60', and by development of
      ophthalmoplegia on the following day. Hyperdens patches on the CT scan showed
      haemorrhage into the tumor. A chromophobic adenoma with macroscopic and
      histological signs of haemorrhage was removed via the transsphenoidal route. In
      the postoperative period the ophthalmoplegia gradually disappeared but central
      hypoadrenia and hypothyroidism occurred. This is the second case in the
      literature showing that TRH alone and in a low dose may cause pituitary tumor
      apoplexy. It is concluded that TRH-testing is a risk for the patient with
      pituitary apoplexy. If, due to the size of the tumor the patients have to be
      operated on in any case, and the test is not of essential diagnostic value, the
      TRH-test should be done only in selected cases. Its use in the postoperative
      evaluation however is without risk for the patients.

PMID- 9285213
TI  - Current therapy of hypoparathyroidism--a survey of German endocrinology centers.
AB  - Hypoparathyroidism is a rare disease with hypocalcemia as the leading symptom. In
      adults, hypocalcemia is mainly due to postoperative hypoparathyroidism.
      Hypoparathyroidism requires lifelong therapy with vitamin D or metabolites.
      Genuine vitamin D3 (Vigantol) is the most economic treatment of
      hypoparathyroidism; however, vitamin D3 has a very long biologic half life with
      the subsequent danger of chronic vitamin D intoxication. Dihydrotachysterol
      (A.T.10), an analogue of vitamin D, acts similarly and can be used alternatively.
      1,25-dihydroxyvitamin D3 (Rocaltrol), the biologically active metabolite of
      vitamin D3, is very potent, but bears the danger of causing acute intoxication;
      it has a short half life and is more expensive than vitamin D3. A further
      metabolite, 1-hydroxy-vitamin D3 (alfacalcidol, Doss, EinsAlpha) is available for
      therapeutic use. Clinical intervention trials concerning the best therapy and
      management of hypoparathyroidism are lacking. We therefore surveyed German
      physicians treating hypoparathyroidism. Furthermore, we carried out a
      retrospective study of 45 patients treated in our endocrinology department during
      the last 8 years and examined whether measurement of 25(OH)-vitamin D3 is helpful
      in managing hypoparathyroidism. The data from 59 children and 270 adults could be
      completed in the survey. 1,25-dihydroxyvitamin D3 was the only vitamin D agent
      that was administered in the treatment of children, whereas in adults 52% were
      treated with dihydrotachysterol, 28% with genuine vitamin D3, and 20% with 1,25
      dihydroxyvitamin D3. There was a positive correlation between serum 25(OH)
      vitamin D3 levels and administered vitamin D3 doses. In patients treated with
      vitamin D3, serum calcium levels correlated significantly with serum 25(OH)
      vitamin D3 levels whereas they did not correlate with administered calcium doses.
      Thus: (1) in Germany dihydrotachysterol is preferred for therapy of
      hypoparathyroidism in adults and (2) measurement of serum 25(OH)-vitamin D3 may
      be helpful in assessing efficacy of therapy and compliance in patients treated
      with vitamin D3.

PMID- 9285214
TI  - Prognostic value of pattern reversal visual-evoked potentials in idiopathic
      epiretinal membrane.
AB  - BACKGROUND: Prognostically favorable factors for epiretinal membrane removal have
      been described in the literature by several authors. Little information, however,
      is available about the objective assessment of the preoperative macular function.
      This study reports the results of idiopathic epiretinal membrane removal and the
      prognostic value of preoperative, pattern reversal visual-evoked potentials
      (PRVEPS) in recovery of visual acuity (VA). METHODS: In 60 patients (60 eyes)
      with idiopathic epiretinal membrane we performed PRVEP examination
      preoperatively. All eyes were operated on by standard three-port vitrectomy with
      membrane removal. Two eyes were excluded because of postoperative complications.
      Follow-up VA was compared with preoperative VA for the 58 study eyes and
      correlated with preoperative PRVEP parameters. RESULTS: The mean preoperative VA
      was 0.2, the mean postoperative VA, 0.4. The PRVEP was recordable in 74%, 67% and
      36% of cases for check sizes of 17, 10 and 7 arcmin respectively. Twenty patients
      (50%) had an increase in VA of two lines or more, in 25 patients (43%) VA
      remained within one line of the preoperative value, and in 4 patients (7%) VA
      decreased by two lines or more. The mean preoperative VA was not significantly
      different between the group with an improved VA and the group that did not
      benefit from membrane removal. Of the PRVEP parameters, only the N80 latency for
      the 17' check size was significantly associated with postoperative visual
      outcome. CONCLUSION: The PRVEP is applicable as a predictor for visual outcome in
      cases of epiretinal membrane removal. For the 17' pattern size we found a
      significant association of the combination of recordability and delayed N80
      latency with visual outcome.

PMID- 9285215
TI  - The corneal stroma: an inhomogeneous structure.
AB  - PURPOSE: This study was conducted to determine the elemental composition of the
      human cornea. Special attention was paid to corneal stroma inhomogeneity.
      METHODS: Seventy human corneas were examined by means of energy-dispersive X-ray
      analysis. Epithelium, subepithelium, middle stroma, sub-Descemet layer,
      Descemet's membrane and endothelium were subjected to repeated measurements.
      RESULTS: In the cellular layers the phosphorus concentrations were high [0.35
      mol/kg dry weight (dw) in the epithelium and 0.403 mol/kg dw in the endothelium].
      Similar concentrations were found for sulphur (0.38 mol/kg dw in the epithelium).
      Stromal layers showed high contents of sulphur: 0.26 mol/kg dw. The phosphorus
      concentration was found to be higher in the subepithelium than in the middle
      stroma. Sulphur concentrations were highest in Descemet's membrane, followed by
      the subepithelium and the middle stroma. DISCUSSION: Nucleic acids and energy
      containing phosphates explain the high levels of phosphorus in the cellular
      layers. The high sulphur concentrations may be related to the
      phosphoadenosinphosphosulfate and protein turnover in the epithelium. We
      interpret the inhomogeneous distribution of phosphorus in the stroma as a
      function of the density of keratocytes. An evaluation of all known sulphur
      containing biochemical components of the stroma (0.217 mol sulphur/kg dw)
      corresponds to our measurements. In contrast to former results we find the
      corneal stroma to be an inhomogeneous structure.

PMID- 9285216
TI  - Frontalis suspension in the treatment of essential blepharospasm unresponsive to
      botulinum-toxin therapy: long-term results.
AB  - Thirty-one patients with essential blepharospasm or lid opening disorder of the
      levator-inhibiting type, unresponsive to treatment with botulinum toxin,
      underwent frontalis suspension. Twenty-eight patients received bilateral surgery
      (three patients with bilateral complaints of different severity were operated on
      the more affected side; these patients were not included in the statistical
      analysis). The mean age was 62.4 years +/- 8.52 (range 42-80 years). The
      individual improvement of complaints was assessed by the patients using a
      percentage scale (0% = no improvement; 100% = no complaints). Objective and
      subjective improvement was achieved in 26 of 28 patients. The mean subjective
      improvement was 57.7% +/- 31.4. In 23 cases an additional treatment with
      botulinum toxin was administered. During follow-up period (mean 22.1 months +/-
      11.6; range 5-40 months) the effect of surgery remained stable. There were no
      serious complications, in a 5 of 56 operated eyes suture granuloma had developed.
      Unlike other surgeries for treatment of blepharospasm (excision of the
      orbicularis muscle, resection of facial nerve branches) frontalis suspension can
      be considered as a minimally invasive, but very effective and (if desired)
      reversible procedure. Moreover, additional treatment with botulinum toxin can
      bring about further improvement.

PMID- 9285217
TI  - Familial exudative vitreoretinopathy: surgical intervention and visual acuity
      outcomes.
AB  - BACKGROUND: Familial exudative vitreoretinopathy (FEVR) is a hereditary condition
      that may lead to vitreous hemorrhage and traction retinal detachment
      necessitating surgical intervention. In this paper we review the results of
      surgery on seven such patients (eight eyes). METHODS: Seven patients (eight eyes)
      were followed up after surgery that had been performed because of vitreous
      hemorrhage and/or traction retinal detachment due to FEVR, in an effort to
      evaluate outcomes. Parameters that were noted were the current age, gender, age
      at the time of first surgery, length of follow-up and postoperative retinal
      status and visual acuity. RESULTS: Seven patients (eight eyes) ranging in age
      from 6 months to 44 years with a mean of 24.7 and a median of 26 years were
      followed. There were three females and four males. The lowest age at which
      surgery was first performed was 6 months and the highest was 28 years, with a
      mean of 14.7 and a median of 17 years. Six of the 8 eyes were reattached
      following surgery, although some required multiple procedures. CONCLUSION:
      Vitreoretinal surgery may be of benefit in helping to preserve some degree of
      vision in eyes of patients with FEVR who develop vitreous hemorrhage and/or
      retinal detachment.

PMID- 9285219
TI  - Early detection of P-VEP and PERG changes in ophthalmic Graves' disease.
AB  - BACKGROUND: In Graves' disease the optic neuropathy (ON) is due to direct
      compression of the nerve and/or of its blood supply. The aim of the present study
      was to detect early changes in the visual functions of patients affected by
      ophthalmic Graves' disease (OGD) by using electrophysiological tests (P-VEP and
      PERG). METHODS: We studied 50 OGD patients who were in a range between class 2
      and class 5 according to the Donaldson-American Thyroid Association
      classification, i.e. had no evident ON and normal visual acuity. We recorded
      transient reversal PERG and P-VEP in response to the stimulation of one eye at
      three spatial frequencies (2.2, 1.1 and 0.5 c/d). RESULTS: Our results showed a
      statistically significant reduction in PERG amplitude in class 5, while the P-VEP
      amplitude was already reduced in class 2. CONCLUSION: The electrofunctional tests
      were useful to detect small changes in the visual function of patients affected
      by initial stages of OGD. Therefore, P-VEP and PERG recordings appear to be a
      useful tool for early diagnosis of the optic nerve involvement in Graves'
      disease.

PMID- 9285218
TI  - Pupil response triggered by the onset of coherent motion.
AB  - BACKGROUND: Recent studies have shown that transient constrictions of the pupil
      can be elicited by visual stimuli that do not cause an increment in light flux
      level on the retina. Such stimuli include achromatic gratings and isoluminant
      chromatic patterns. METHOD: We investigated pupillary responses to the onset of
      coherent movement generated in a pattern of dots in random motion. Measurements
      were carried out in normal observers and in a subject with hemianopia caused by
      damaged primary visual cortex. RESULTS: The experimental findings show that the
      onset of coherent motion triggers systematic constrictions of the pupil that
      cannot be accounted for in terms of a pupil light reflex response. We labelled
      these constrictions Pupil motion responses (PMRs). Results show that PMRs have
      large response latencies and on average are of small response amplitudes. The
      dependence of PMRs on changes in motion parameters such as stimulus speed and
      direction of motion has been investigated. CONCLUSIONS: The existence of PMRs to
      the onset of the coherent motion in human vision has been demonstrated. These new
      findings are discussed in relation to the psychophysical and physiological data
      on motion perception and the possible pathways involved in the control of the
      pupil response.

PMID- 9285220
TI  - Cell types of secondary cataract: an immunohistochemical analysis with antibodies
      to cytoskeletal elements and macrophages.
AB  - BACKGROUND: The study was carried out to identify cell types of secondary
      cataract after extracapsular cataract extraction and implantation of an
      intraocular lens. METHODS: Twenty-five formalin-fixed, paraffin-embedded
      pseudophakic human eyes with secondary cataract, obtained at autopsy, were
      studied and compared to a specimen from an anterior subcapsular cataract with a
      panel of six monoclonal antibodies (MAbs, to vimentin, cytokeratin (CK) 8 and 18,
      desmin, alpha-smooth muscle actin, and the CD68 epitope of macrophages by the
      avidin-biotinylated peroxidase complex (ABC) method. RESULTS: MAb Vim 3B4 to
      vimentin immunolabeled spindle-shaped cells in 16 of 17 central plaques of
      secondary cataract as well as cells in all 16 Soemmering's ring cataracts.
      Spindle-shaped cells reacted with MAb CAM 5.2 to CK 8 in 13 of 18 eyes, but only
      one specimen was labeled with MAb CY-90 to CK 18. No immunoreaction was seen with
      MAb D33 to desmin, whereas MAb 1A4 to alpha-smooth muscle actin immunolabeled
      spindle-shaped cells in 15 of 18 plaques of secondary cataract. Macrophages were
      seen with MAb PG-M1 in 13 of 19 secondary cataracts. In the anterior subcapsular
      cataract, spindle-shaped cells under a wrinkled but otherwise intact capsule
      reacted with MAb Vim 3B4 to vimentin, MAb CAM 5.2 to CK 8, and MAb 1A4 to alpha
      smooth muscle actin. CONCLUSION: Spindle-shaped cells in secondary and anterior
      subcapsular cataracts react with antibodies to vimentin, CK 8 and alpha-smooth
      muscle actin, suggesting them to be metaplastic epithelial cells that derive from
      the lens epithelium. alpha-Smooth muscle actin persists in them at least 10 years
      postoperatively, but CK 8 starts to disappear after 3 years. Macrophages are one
      possible modulator of this transdifferentiation.

PMID- 9285221
TI  - Ocular manifestations in a father and son with EEC syndrome.
AB  - BACKGROUND: The ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome is a
      rare disease which follows an autosomal-dominant pattern of inheritance. Due to
      the ectodermal dysplasia there is atresia of the lacrimal duct system and aplasia
      of the meibomian glands with a defective tear film. Therefore, vascularized
      corneal scars often form during early adult life. PATIENTS: Father aged 41 years,
      and son aged 23 months. Both patients: stenosis/atresia of lacrimal duct systems
      (the father had twice undergone dacryocystorhinostomy externally) with epiphora,
      lip-palate clefting, syndactylies of fingers and toes, lobster deformities of
      hands. Additional ophthalmological findings in the father: bilaterally extracted
      juvenile cataracts with implantation of intraocular lenses, bilateral extensive
      vascularized corneal scars. Additional dermatological findings in the father:
      malignant melanoma of the calf, now in complete remission following several
      operations on the melanoma and several cycles of chemotherapy for the metastases.
      DISCUSSION AND THERAPEUTIC CONCLUSIONS: Father and son show the full clinical
      picture of the EEC syndrome with clefting, lobster-like deformities of the hands
      and ectodermal dysplasia with tear duct atresia and aplasia of the meibomian
      glands with defective tear film. During childhood, the main handicapping features
      are the clefting and the hand deformities with their respective multiple
      operative revisions. During early adulthood, however, the ocular problems become
      the predominantly handicapping aspects of the EEC syndrome; due to the ectodermal
      dysplasia, vascularized corneal scarring develops. Tearing and secondary
      inflammation due to lacrimal duct atresia has to be treated by early
      dacryocystorhinostomy. As secondary infections promote the development of corneal
      scars, one should not postpone the operation too long. Infections have to be
      treated promptly by local antibiotics. Because of the aplasia of the meibomian
      glands, artificial tear substitution should be given on a regular basis to
      support the defective tear film. Thus, the development of vascularized corneal
      scars can perhaps be delayed. Once corneal scarring has developed, perforating
      keratoplasty has a poor prognosis due to the ectodermal dysplasia, the absence of
      the meibomian glands and the defective tear film. Three factors lead to the
      formation of vascularized corneal scars: recurrent infections of lid margins and
      conjunctiva due to obstructed tear ducts; defective tear film with insufficient
      lipid phase due to the aplasia of the meibomian glands; and primary corneal
      epithelial defects in the course of the generalized ectodermal dysplasia.

PMID- 9285222
TI  - Deposition of extracellular matrix on silicone intraocular lens implants in
      rabbits.
AB  - PURPOSE: To examine the deposition of extracellular matrix on silicone
      intraocular lenses (IOLs) implanted experimentally into rabbit eyes by electron
      microscopy and to determine the immunolocalization of extracellular matrix
      components, including collagen types and cellular fibronectin, on these IOLs.
      METHODS: We performed phacoemulsification and aspiration of the crystalline lens
      and implanted a foldable silicone IOL in the capsular bag of one eye of each of
      26 adult albino rabbits under general anesthesia. After 8 weeks the animals were
      killed and the eyes were enucleated. The silicone IOLs were processed for
      electron microscopy and for immunohistochemical detection of collagen types I,
      III, and IV and cellular fibronectin. RESULTS: Electron microscopy revealed
      deposition of a presumed cell matrix complex on the optic portion of all silicone
      IOLs, as well as the adhesion of presumed macrophages and foreign-body giant
      cells. Cellular deposits showed immunoreactivity for cellular fibronectin.
      Fibrous or membranous deposits exhibited immunoreactivity for cellular
      fibronectin and collagen types I and III. A few type IV collagen-immunoreactive
      deposits were also seen. CONCLUSION: Deposits of extracellular matrix components
      were observed on silicone IOLs. These deposits may form the scaffolding for the
      adhesion and proliferation of cells. These matrix components appeared to be the
      products of cells adhering to the surfaces of IOLs, including lens epithelial
      cells, macrophages and foreign-body giant cells, indicating that the process of
      granulation was incomplete.

PMID- 9285223
TI  - Macular holes: migratory gaps and vitreous as obstacles to glial closure.
AB  - PURPOSE: Retinal glia may play an important role in the closure of macular holes.
      This in vitro study examines whether and how the specific pathoanatomy, including
      foveal eversion and foveal vitreous, may interfere with glial closure of macular
      holes. METHODS: Culture dishes used to grow glial cells were modified by the
      placement of slopes, vertical steps, and gaps to mimic the in vivo migratory
      surface in and surrounding macular holes. In separate experiments, defects were
      made in a rodent glial monolayer. These defects were exposed to hyaluronic acid
      (HA) and to rabbit (RV) and bovine (BV) vitreous gel. The migratory behavior and
      completeness of closure of defects were compared to controls. RESULTS: As
      expected, glial cells migrated further and in greater numbers on a smooth
      surface. Slopes and steps were moderate obstacles to migration; gaps in the
      surface were absolute obstacles. HA modified the pattern of adhesion of cells at
      the bottom of defects. Defects in the glial monolayer were repaired in 5-7 days.
      Compared to these controls, repair was inhibited by 11% (n.s.), 28% (P = 0.02),
      and 58% (P = 0.004) after direct exposure of defects to HA, RV and BV,
      respectively. CONCLUSION: The elevated and everted margins of macular holes
      represent slope, step, and gap-like obstacles to the migration of glial cells and
      hence to the healing of defects. The defect allows extension of extracellular
      matrix into it and the subretinal space. Our results indicate that gaps in the
      migratory surface caused and aggravated by eversion and the presence of vitreous
      present obstacles to glial migration and closure of macular holes.

PMID- 9285224
TI  - The in vitro effect of platelet-derived growth factor isoforms on the
      proliferation of bovine corneal stromal fibroblasts depends on cell density.
AB  - PURPOSE: Recently, it has been shown that corneal stromal fibroblasts express the
      mRNA for PDGF-beta-type receptors, while corneal epithelial cells express the
      mRNA for the PDGF B-chain, suggesting a role of PDGF isoforms in the regulation
      of corneal homeostasis and wound healing via an unidirectional epithelial to
      stromal paracrine interaction. The purpose of this study was to characterize the
      proliferative response of cultured bovine corneal stromal fibroblasts to PDGF
      isoforms. METHODS: Bovine corneal stromal fibroblasts were seeded at a cell
      density of 60 cells/mm2 (low density) and 120 cells/mm2 (high density) and were
      cultured under serum-free conditions. Except for corresponding controls, PDGF AA,
      BB and AB (obtained by separate expression of cloned genes in E. coli) were added
      in concentrations ranging from 3.125 to 100 ng/ml. Cell numbers were determined
      after an incubation period of 6 days using a cell counter. RESULTS: Stromal
      fibroblasts, when cultured at a high density, revealed constant cell numbers
      during the whole incubation period. Under these culture conditions, stimulation
      with PDGF AA, BB and AB led to a significant dose-dependent increase in cell
      proliferation. When cultured at a low cell density, stromal fibroblasts revealed
      a significant reduction of cell numbers after 6 days of incubation. This
      reduction was prevented by PDGF AA and AB isoforms in a dose-dependent manner. In
      contrast, PDGF BB was not effective. CONCLUSION: The results of the "high
      density" assays suggest that PDGF isoforms act as mitogens for stromal
      fibroblasts during wound healing, when density of fibroblasts is high. The
      results of the "low-density" assays support the idea that PDGF AA and AB can
      prevent cell loss during corneal homeostasis when density of keratocytes is low.

PMID- 9285225
TI  - Inhibition of corneal allograft reaction by CTLA4-Ig.
AB  - BACKGROUND: Activation of T cells requires both the interaction of T-cell
      receptor with major histocompatibility complex on the antigen-presenting cell and
      costimulatory signals, for instance the B7 antigens expressed on antigen
      presenting cells and the CD28 molecule expressed on T cells. A recombinant fusion
      protein, CTLA4-Ig, has been produced that contains the extracellular domain of
      human CTLA4 fused to IgG1 constant region and that binds the B7 molecule with
      high affinity. Blocking the CD28/B7 interaction with CTLA4-Ig inhibits T cell
      activation in vitro and in vivo. METHODS: We used CTLA4-Ig in a fully MHC
      mismatched mouse keratoplasty model. The animals were divided into four groups:
      (1) no treatment, (2) intraperitoneal treatment with 130 micrograms CTLA4-Ig, (3)
      intraperitoneal treatment with 300 micrograms CTLA4-Ig, (4) subconjunctival
      treatment with 290 micrograms CTLA4-Ig. RESULTS: The allograft reaction occurred
      in untreated animals between days 12 and 16 (mean 13.5). While topical
      application of CTLA4-Ig seemed to shorten the graft survival (mean 11.6 days) and
      systemic application of 130 micrograms had no influence (mean 14.0), only
      intraperitoneal injection of 300 micrograms of CTLA4-Ig prolonged the survival of
      allografts (mean > 20 days) (P < 0.01). CONCLUSION: CTLA4-Ig prolonged
      significantly the survival of corneal allografts in a fully MHC-mismatched mouse
      keratoplasty model, but the small antigen load of the corneal transplant and the
      anterior chamber-associated immune deviation (ACAID) may have a disadvantage to
      induce tolerance in this model of CTLA4-Ig therapy.

PMID- 9285226
TI  - Choroidal metastasis of mixed carcinoma of the parotid gland.
AB  - BACKGROUND: A case of mixed carcinoma of the parotid gland (an epidermoid
      carcinoma located in a pleomorphic adenoma) metastatic to the choroid is
      presented. The histopathology of the tumor is discussed. METHODS: A 65-year-old
      man was admitted complaining of blurred vision in his right eye for 1 day. He
      underwent parotidectomy for mixed carcinoma of the parotid gland (an epidermoid
      carcinoma located in a pleomorphic adenoma that was completely excised) 6 months
      before. Funduscopic examination showed a nasal retinal detachment, with gray
      whitish, minimally elevated nodular choroidal lesions. Fluorescein angiography
      and contact B-scan ultrasonography confirmed the presence of an underlying mass.
      RESULTS: The right eye was enucleated and an epidermoid infiltrating carcinoma
      was identified. CONCLUSIONS: Metastatic tumors are the most common intraocular
      malignancies, and the choroid is by far the most common location for intraocular
      metastases. There are few cases reported of parotid tumors metastatic to the
      orbit. To the best of our knowledge, no histological examination of an ocular
      metastatic mixed carcinoma of the parotid gland has yet been reported.

PMID- 9285227
TI  - Pulling cost-effectiveness analysis up by its bootstraps: a non-parametric
      approach to confidence interval estimation.
AB  - The statistic of interest in the economic evaluation of health care interventions
      is the incremental cost effectiveness ratio (ICER), which is defined as the
      difference in cost between two treatment interventions over the difference in
      their effect. Where patient-specific data on costs and health outcomes are
      available, it is natural to attempt to quantify uncertainty in the estimated ICER
      using confidence intervals. Recent articles have focused on parametric methods
      for constructing confidence intervals. In this paper, we describe the
      construction of non-parametric bootstrap confidence intervals. The advantage of
      such intervals is that they do not depend on parametric assumptions of the
      sampling distribution of the ICER. We present a detailed description of the non
      parametric bootstrap applied to data from a clinical trial, in order to
      demonstrate the strengths and weaknesses of the approach. By examining the
      bootstrap confidence limits successively as the number of bootstrap replications
      increases, we conclude that percentile bootstrap confidence interval methods
      provide a promising approach to estimating the uncertainty of ICER point
      estimates. However, successive bootstrap estimates of bias and standard error
      suggests that these may be unstable; accordingly, we strongly recommend a
      cautious interpretation of such estimates.

PMID- 9285228
TI  - Saving future lives. A comparison of three discounting models.
AB  - This paper compares three models of intertemporal choice concerning saving future
      lives: the constant discounting model, the proportional discounting model and the
      hyperbolic discounting model. The three models were investigated using data
      collected from the general public. Since these data have a multilevel structure,
      ordinary least-squares (OLS) estimates were supplemented by multilevel analysis.
      There is evidence in favour of the proportional (and to a lesser extent) the
      hyperbolic model over the constant discounting model. There is clear evidence for
      this data set that multilevel analysis is more appropriate than OLS.

PMID- 9285229
TI  - Towards an economic model of the Dutch health care sector.
AB  - This paper describes the construction of a model of the Dutch health care sector.
      It discusses the behaviour of patients, general practitioners, medical
      specialists and hospital managers. It also analyses the various ways the actors
      interact, such as general practitioners supplying the services demanded by
      patients, specialists dispatching referrals made by general practitioners or
      hospital managers boosting output to match an increasing amount of specialist
      services. Numerical simulations illustrate the various mechanisms in the model.

PMID- 9285230
TI  - Health care policy evaluation using longitudinal insurance claims data: an
      application of the panel Tobit estimator.
AB  - The British Columbia Ministry of Health provides enhanced prescription drug
      insurance coverage to residents aged 65 and older. This exogenous change in the
      effective price of prescription drugs is used to investigate aspects of the drug
      use by seniors. Three sets of issues are of interest. First, what is the effect
      of enhanced insurance coverage on drug use and programme costs once drugs are
      provided free of charge? Second, is this effect permanent, or transitory? Third,
      are any increases in use observed concentrated among those with lower incomes?
      Longitudinal administrative claims payment data on 18,000 seniors over the period
      1985-92 are used. All individuals in the sample turned 65 at some point and
      therefore became eligible for subsidized prescription drugs. Health status
      information is not collected; instead, health status is treated as an individual
      specific fixed endowment, subject to a common rate of decay. Estimation is
      complicated by censoring of real drug expenditures for those under 65, rendering
      'first differencing' methods invalid. A semi-parametric fixed effects Tobit
      estimator is used instead. For most individuals, the extension of insurance does
      not permanently increase drug use. Males with lower income were the exception.
      Little evidence of transitory effects to insurance coverage was found. Finally,
      the extension of insurance has made only a minor contribution to growth in
      seniors' drug use, relative to secular growth in drug use over time.

PMID- 9285231
TI  - Estimating surgical volume--outcome relationships applying survival models:
      accounting for frailty and hospital fixed effects.
AB  - This paper investigates the surgical volume-outcome relationship for patients
      undergoing hip fracture surgery in Quebec between 1991 and 1993. Using a duration
      model with multiple destinations which accounts for observed and unobserved (by
      the researcher) patient characteristics, our initial estimates show that higher
      surgical volume is associated with a higher conditional probability of live
      discharge from the hospital. However, these results reflect differences between
      hospitals rather than differences within hospitals over time: when we also
      control for differences between hospitals that are fixed over time, hospitals
      performing more surgeries in period t + 1 than in period t experience no
      significant change in outcomes, as would be predicted by the 'practice makes
      perfect' hypothesis. The volume-outcome relationship for hip fracture patients
      thus appears to reflect quality differences between high and low volume
      hospitals.

PMID- 9285232
TI  - Down and out: estimating the relationship between mental health and unemployment.
AB  - We utilized a unique dataset of Montreal residents to estimate the relationship
      between employment and mental health, controlling for endogeneity. We applied a
      maximum likelihood, simultaneous equation generalized probit model to estimate
      jointly the determinants of an individual's latent index of employability and
      their mental health as measured by the Psychiatric Symptom Index (PSI). The
      likelihood function was adjusted to account for the fact that individuals were
      sampled based on their employment status, and also for the fact that repeated
      observations of individuals in different periods were used in the analysis. We
      found tangible beneficial effects of mental health on employability. In addition,
      employment appears to improve mental health. The ML estimates of the endogenous
      relationship between employment and mental health indicate that OLS estimates are
      biased upwards, but the effects of unemployment on deteriorating mental health
      are not spurious.

PMID- 9285233
TI  - Age related health dynamics and changes in labour market status.
AB  - We focus on aspects of health changes, the importance of cohort effects, age
      related health changes and the effect of labour market status and work history on
      health. We moreover assess the relative importance of gradual changes and sudden
      shocks in health changes and the role of work status on the likelihood of
      experiencing a health shock. A fixed effect panel data model is estimated on two
      waves of a survey of Dutch elderly. We find strong differences in health outcomes
      for different age cohorts and gender. We also find that health deteriorates with
      employment and labour market history.

PMID- 9285234
TI  - The impact of health on retirement behaviour: empirical evidence from West
      Germany.
AB  - In this paper, the relative importance of an individual's health status on
      retirement behaviour is analysed within the framework of a structural, discrete
      time hazard rate model which is estimated using a balanced panel of elderly West
      German men. The results obtained reveal that the presence of chronic complaints
      or disability have a significant positive impact on the probability of early
      retirement. Moreover, the relative intensity of the individual preference for
      leisure appears to be, ceteris paribus, below average among public sector
      employees. Education, too, is shown to exert considerable influence on retirement
      behaviour, but the relationship between an individual's educational status and
      the probability of early retirement appears to be rather complex. A policy
      related simulation experiment based on the estimates is carried out in order to
      assess the effects of changes in the incentive structure of the existing pension
      scheme.

PMID- 9285235
TI  - Cluster effects and simultaneity in multilevel models.
AB  - For small group sizes, the GLS estimator in multilevel models is biased and
      inconsistent when the random cluster effects are correlated with the regressors.
      A fixed effects approach, conditioning on the cluster effects, provides
      consistent estimates for the slope parameters. The two estimators are equivalent
      when group sizes are large. The same results obtain for two-stage estimation
      procedures that allow for some of the regressors to be simultaneously determined
      with the dependent variable. The GLS and fixed effects estimators are applied to
      data on acute care hospital utilization in the UK, allowing for health authority
      district effects.

PMID- 9285236
TI  - Is endstage heart disease really terminal?

PMID- 9285237
TI  - Patients' profiles in end stage coronary artery disease. Indications for
      treatment with transmyocardial laser revascularisation.
AB  - There is a subgroup of patients with coronary artery disease who are refractory
      to the therapeutical methods so far applied. We report on 128 patients who
      fulfill this definition and have therefore undergone pure transmyocardial laser
      revascularisation (TMLR) or transmyocardial laser revascularisation in
      combination with coronary bypass surgery at our institution. The patients can be
      characterized by a long history of coronary artery disease with multiple
      revascularizing procedures, e.g. bypass surgery or percutaneous transluminal
      coronary angioplasty (PTCA), pronounced symptoms of coronary artery disease and
      chronic heart failure in the presence of markedly reduced left ventricular
      ejection fractions and intense antiischemic medical therapy. The patients were
      62.2 +/- 9.8 (SD) years of age, in 89.9% of them at least one bypass operation
      and in 44.5% up to more than three percutaneous transluminal coronary
      angioplasties (PTCAs) had been performed prior to TMLR. There was a history of
      myocardial infarction in 90.7% of patients and 89.8% were in the Canadian
      Cardiovascular Society (CCS) classes III or IV and 94.5% of them were in the NYHA
      classes III or IV. The left ventricular ejection fraction was 49.5 +/- 16.4% and
      all of the patients were under intense antiischemic medical treatment which
      included nitrates or molsidomine in 96.9%, beta blockers in 53.1%, angiotensin
      converting enzyme inhibitors (ACE inhibitors) in 44.5%, digitalis in 22.7% and
      diuretics in 52.3% of patients. The preoperative data on myocardial viability,
      inducible ischemia and coronary morphology provided important clinical
      information for the decision, which revascularizing method would be the most
      appropriate for each vessel or myocardial region. This had to be weighed against
      the patient's operative risk, which is predominantly determined by the left
      ventricular ejection fraction, the arteriosclerotic involvement of the remaining
      vascular system and concomitant diseases, particularly of pulmonary origin.

PMID- 9285238
TI  - Attenuated Trypanosoma cruzi infection in young rats nursed on infected mothers
      undergoing interferon-gamma treatment during pregnancy.

PMID- 9285239
TI  - Intravenously administered macrophage colony-stimulating factor (M-CSF)
      specifically acts on the spleen, resulting in the increasing and activating
      spleen macrophages for cytokine production in mice.
AB  - IL-6 was transiently expressed in sera of mice after a bolus intravenous
      injection with LPS and it peaked 2 h later. Intravenous administration of M-CSF
      at 250 micrograms/kg/day for 5 days prior to an injection of 25 micrograms/kg of
      LPS elevated the serum IL-6 level 10-fold higher than that of mice which were not
      given M-CSF. Although M-CSF had no effect on the number of macrophages in alveoli
      and peritoneal cavity, it tripled the number of spleen macrophages and increased
      macrophage-progenitor cells 7-fold when injected intravenously. Spleen
      macrophages from M-CSF-injected mice produced 5-fold more IL-6 in response to LPS
      stimulation in-vitro. However, M-CSF-injection had lesser effects on LPS-induced
      IL-6 production from liver, alveolar and peritoneal macrophages. Exogenously
      administered M-CSF was detected at higher concentration and for longer duration
      in the spleen than in any other organs examined. Spleen macrophages incubated in
      vitro with more than 1000 U/ml of M-CSF for 3 days also produced more LPS-induced
      IL-6 than untreated cells. These results indicate that intravenously administered
      M-CSF not only enhances macrophage development in the spleen, but also primes
      mature macrophages for cytokine production.

PMID- 9285240
TI  - Macrophage colony-stimulating factor (M-CSF) augments cytokine induction by
      lipopolysaccharide (LPS)-stimulation and by bacterial infections in mice.
AB  - We studied the effects of M-CSF on cytokine induction in vivo by LPS or by
      bacterial infection by comparing between the serum cytokine levels of mice
      administered with and without M-CSF. M-CSF at 250 micrograms/kg/day for 3 days
      significantly augmented serum IL-6 level induced by a subsequent injection of 25
      micrograms/kg of LPS. The augmented IL-6-induction was dose-dependent from 50 to
      1250 micrograms/kg/day of M-CSF, and required 2- to 3-doses of M-CSF at 250
      micrograms/kg/day. Mice primed with M-CSF induced IL-6 in response to a 5-fold
      lower dose of LPS, and also produced higher levels of IL-1 alpha, IL-10, GM-CSF,
      TNF-alpha, and IFN-gamma than control mice. The priming effect of M-CSF was
      transient and reversible, and elicited independently of T-cells. An injection
      with intact bacteria, such as Gram-negative Escherichia coli and Gram-positive
      Staphylococcus aureus also induced IL-6 in normal mice, and M-CSF administration
      augmented the induction of these cytokines. These results showed that M-CSF
      positively regulates LPS-dependent and -independent cytokine induction,
      suggesting a defensive effect against infectious agents through enhanced cytokine
      production.

PMID- 9285242
TI  - Nitric oxide and antimicrobial activity of reactive oxygen intermediates.
AB  - It is well documented that nitric oxide contributes to the bactericidal
      activities of phagocytes. Murine activated neutrophils and macrophages produce
      both reactive oxygen intermediates (ROI) and reactive nitrogen intermediates
      (RNI). However, only neutrophils in the presence of myeloperoxidase, produce an
      antimicrobial agent, hypochlorous acid (HOCl). Complex interactions of RNI
      (nitric oxide) with other antimicrobial agents of phagocytes are likely to exist,
      but these have not been clearly demonstrated. In this study, we treated bacteria
      (Escherichia coli) with the NO donor, S-nitrosoglutathione (GSNO) and hydrogen
      peroxide (H2O2) or HOCl. We found that exposure to H2O2 of the bacteria tested
      resulted in minimal toxicity. However the killing activities of H2O2 were
      potentiated by GSNO. On the contrary, the NO-donor completely abolished the
      bactericidal activity of HOCl. Our results indicate that NO-donating drugs in non
      toxic concentrations used for experimental purposes may strongly affect the
      cytotoxic activity of neutrophils and macrophages. We suggest that the similar
      interactions may exist at sites of inflammation.

PMID- 9285243
TI  - Tuftsin-THF-gamma 2 chimeric peptides: potential novel immunomodulators.
AB  - Synthesis of two chimeric peptides composed of tuftsin and thymic humoral factor
      gamma 2 (THF-gamma 2) conjugates was accomplished. Our goal was the generation of
      novel immunomodulators. Initially, we demonstrate an IL-6 inducing activity of
      the phagocytic cells stimulant, tuftsin, on murine macrophages. This activity was
      documented only in the presence of antigen, either KLH or lysozyme. The
      augmentation was dose dependent, with optimal activity at a concentration of 200
      and 20 nM, respectively. The chimeric peptides, either H2N-tuftsin-THF-gamma 2-OH
      or H2N-THF-gamma 2-tuftsin-OH, were also evaluated in the IL-6 system in the
      presence of the more potent antigen, KLH. The IL-6 inducing effect was
      maintained, although maximal activity appeared only at a concentration an order
      of magnitude greater than that of tuftsin. The chimeric peptides were further
      tested in an assay evaluating enhancement in murine bone marrow myeloid colony
      formation, a system in which THF-gamma 2, a T cell stimulant, has an established
      beneficial effect. The compounds were found to be inactive at the 25-200 ng/ml
      (14-112 nM) concentration range evaluated. Finally, the chimeric peptides were
      tested in a combined macrophages-T cells assay, i.e. antigen presentation, in
      which H2N-tuftsin-THF-gamma 2-OH was found to be more active than either parent
      peptide, thus representing a possible therapeutic agent.

PMID- 9285241
TI  - Disruption of Th1/Th2 cytokine balance by cocaine is mediated by corticosterone.
AB  - Cocaine has been shown to affect immune function through the release of
      corticosterone. Acute administration of both cocaine and corticosterone produces
      an enhancement of the T-dependent antibody response to sheep erythrocytes. The T
      independent antibody response to DNP-ficoll is not enhanced under identical
      conditions, suggesting that the T-cell is involved as a cellular target. We
      examined T-helper cell cytokine production following in vivo cocaine
      administration and found an increase in IL-4 and IL-10; while IL-2 and IFN-gamma
      were unaffected. The rise in Th2 cytokines is consistent with an enhanced T
      dependent antibody response, a measure of humoral immunity. Because previous
      results showed that the enhancement by cocaine is mediated via corticosterone,
      the direct effects of corticosterone on Th1/Th2 in vitro cytokine production were
      investigated. Th1 cytokines, IL-2 and IFN-gamma, were dose-dependently suppressed
      by corticosterone at physiologic concentrations. In contrast Th2 cytokines, IL-4
      and IL-10, exhibited a biphasic dose response curve, whereby an enhancement was
      observed at low doses, followed by suppression at higher doses. In order to
      determine the consequences of this apparent shift towards a Th2 response on a Th1
      response, we looked at the delayed-type hypersensitivity response to sheep
      erythrocytes. This measure of cell-mediated immunity was not significantly
      affected by acute cocaine, however, corticosterone administration resulted in a
      significant suppression. These results indicate that corticosterone can produce a
      shift towards a Th2 predominate response, possibly at the expense of Th1-mediated
      responses.

PMID- 9285245
TI  - Taxol, a microtubule-stabilizing antineoplastic agent, differentially regulates
      normal and tumor-bearing host macrophage nitric oxide production.
AB  - Taxol, a potent antitumor chemotherapeutic, promotes in vitro cytotoxic antitumor
      activities by normal host macrophage (M phi s). Because tumor growth induces
      functional changes among M phi populations, we determined whether fibrosarcoma
      growth (Meth-KDE) modified M phi responsiveness to the activating agent taxol.
      Tumors induce tumor-distal M phi populations to become immune suppressor cells,
      partially through overproduction of the cytotoxic and proinflammatory molecules
      nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha). Beneficial to the
      tumor-bearing host (TBH) when released by tumor-proximal M phi s, NO and TNF
      alpha suppress lymphoproliferation and fail to impart antitumor activity when
      expressed in tumor-distal compartments. We report that taxol differentially
      regulated normal host and TBH M phi production of the immunosuppressive molecule
      NO by tumor-distal M phi populations. In response to IFN-gamma-priming and taxol
      triggering, TBH M phi s increase their production of NO as compared to resting M
      phi s; however, unlike normal host M phi s, taxol-induced TBH M phi NO production
      was significantly suboptimal. Modulation of TBH M phi NO production in tumor
      distal compartments may alleviate M phi-mediated suppression of T-cell
      proliferative responses, yet promote sufficient NO production by tumor-associated
      M phi s to affect cytotoxicity. Collectively, these data leave implications for
      immunotherapeutic activities by the anticancer drug taxol.

PMID- 9285244
TI  - Selective immunomodulatory activity of SK&F 106615, a macrophage-targeting
      antiarthritic compound, on antibody and cellular responses in rats and mice.
AB  - The azaspiranes are novel immunomodulators which are effective in a variety of
      animal models of autoimmune disease and transplantation. The compounds appear to
      target macrophages and alter their functional activity. One of these compounds,
      SK&F 106615 (N,N-diethyl-8,8-dipropyl-2-azaspiro[4.5]decane-2-propanamine++ +
      dihydrochloride), is now in phase II clinical trials for rheumatoid arthritis. As
      many drugs/compounds effective in autoimmune disease and transplantation are
      overtly immunosuppressive, we designed studies to show that SK&F 106615 has
      selective immunomodulatory effects and that it does not perform in a manner
      characteristic of classical immunosuppressive agents on immune function. SK&F
      106615 inhibited mouse and rat spleen cell and rat peripheral blood mononuclear
      cell proliferation in vitro with an IC50 of 500 nM. In vivo, treatment of C57BL/6
      mice (15 mg/kg/day, i.p.) or rats (20 mg/kg/day, p.o.) for 2 weeks had no effects
      on specific antibody synthesis to ovalbumin (OVA) compared to rapamycin (RAP)
      which completely suppressed the antibody response. Compared to cyclosporin A
      (CsA), FK 506 and RAP which suppressed the antibody (plaque forming) response to
      particulate (sheep red blood cells) antigen in a dose responsive manner, SK&F
      106615 administered at a dose of 50 mg/kg was inactive. There was an inhibition
      of the proliferative response of lymph node cells from treated mice and rats to
      mitogen and antigen in ex vivo assays. SK&F 106615, but not RAP, induced cells in
      the spleens of mice that could inhibit normal spleen cell proliferation in a co
      culture assay. Thus, a selective immunomodulatory effect can be shown for SK&F
      106615 in the absence of generalized immunosuppression.

PMID- 9285246
TI  - Short and long-term immunosuppressive effects of clozapine and haloperidol.
AB  - In line with the autoimmune hypothesis of schizophrenia we have tested in this
      study whether the commonly used neuroleptics, clozapine and haloperidol can also
      act as systemic immunosuppressants. Twenty one hospitalized chronic schizophrenic
      patients participated in the study. Five were free of neuroleptic treatment while
      the other 16 were under chronic treatment with either clozapine (n = 8), or
      haloperidol (n = 8). Fourteen age matched normal subjects served as the control
      group. Conventional in vitro mitogenic stimulation of peripheral blood
      lymphocytes with phytohaemagglutinin (PHA) indicated a clear suppression of
      responsiveness of approximately 50% in all treated patients. The PHA response of
      the untreated patients was virtually identical to that of the control group. The
      in vitro effect of haloperidol and clozapine on PHA stimulation of lymphocytes
      from normal subjects was determined by 3H-thymidine uptake and secretion of
      interleukin-2, interleukin-4 and interferon-gamma. Both clozapine and haloperidol
      suppressed thymidine incorporation and cytokine secretion at a drug concentration
      of above 1 microM, reaching full suppression at 50 microM. Similar suppressive
      effects of clozapine and haloperidol were also observed in mixed lymphocyte
      reaction of mouse lymphocytes. Assays with radioactive ligands indicated that
      clozapine is not incorporated into the lymphocytes but presumably exerts its
      action by binding to specific surface sites. The long term immune suppression
      induced by neuroleptic treatment may inhibit putative autoimmune responses
      against neurological sites and could thus act synergistically with the direct
      antagonistic action on brain receptors for the overt amelioration of psychotic
      behaviour.

PMID- 9285247
TI  - Glucocorticoids and cyclosporine induce apoptosis in mitogen-activated human
      peripheral mononuclear cells.
AB  - Induction of apoptosis by immunosuppressive agents such as glucocorticoids (GCs)
      and cyclosporine (CsA) in cultured lymphoid cells has been suggested. However,
      there are few studies which demonstrate the induction of apoptosis by these
      agents in the activation process of human peripheral blood mononuclear cells
      (PBMCs). Here we show that potent immunosuppressive GCs and CsA induce apoptosis
      in concanavalin A (con A)-activated human PBMCs. In this study, GCs and CsA
      suppressed human PBMC-blastogenesis when activated by con A in a dose-dependent
      manner, where healthy PBMCs treated with > 100 ng/ml of each immunosuppressive
      agent exhibited a DNA-ladder structure in electrophoretic analysis. In three
      chronic renal failure (CRF) patients, dose-dependency of the PBMC-apoptosis
      induction was confirmed by our quantification of fragmented DNA using ELISA.
      Furthermore, the enrichment of DNA fragmentation was significantly associated
      with the rate of PBMC-blastogenesis when treated with GCs or CsA (r = -0.466, P <
      0.01). These results suggested that suppression of the mitogen-induced PBMC
      blastogenesis by the immunosuppressive agents should be correlated with the
      induction of apoptosis.

PMID- 9285248
TI  - Study on the mechanism of immunopotentiating antitumor effect of 6-MPG, a water
      soluble derivative of 6-mercaptopurine.
AB  - We investigated possible mechanisms of the antitumor action of gamma-(9H-purine-6
      yl) thiomethyl L-glutamate (6-MPG), a water-soluble derivative of 6-MP. In the
      double grafted tumor system, BALB/c mice were inoculated intradermally with 10(6)
      cells of MethA fibrosarcoma at the right inguinal region on day 0 (the primary
      tumor) and later with 3 x 10(6) cells at the left on day 10 (the secondary
      tumor). Intraperitoneal administration of 6-MPG at a dose of 100 mg/kg/day from
      day 3 through 7 completely prevented growth of the secondary tumor. 6-MPG showed
      no effect on growth of colon 26 adenocarcinoma cells inoculated in place of the
      secondary MethA cells (antigen specificity). 6-MPG did not inhibit the secondary
      MethA growth in the BALB/c (nu/nu) mouse. The inhibitory effect of 6-MPG on the
      secondary tumor growth was diminished by prior treatment of the primed animals
      with cyclosporin A and anti-Thy antibody. Spleen cells from the tumor-bearing
      mice treated with 6-MPG showed a tumor-neutralizing activity (Winn assay).
      Treatment of the spleen cells with anti-CD8 antibody plus complement diminished
      the tumor-neutralizing effect but that with anti-CD4 antibody plus complement did
      not, indicating that CD8-positive cells are responsible for potentiation of the
      tumor immunity. These results suggest that the antitumor effect of 6-MPG against
      the secondary tumor is elicited by augmenting tumor specific T-cell production.

PMID- 9285249
TI  - Changes in cellular composition induced by neocarzinostatin pretreatment in Meth
      A-bearing mice and the responsible antitumor effector cells.
AB  - We previously reported that tumor eradication was induced by a single injection
      of neocarzinostatin (NCS) between 1 day and 4 weeks before Meth A transplantation
      in Balb/c mice via augmenting host-mediated antitumor activity. In order to
      elucidate the mechanism of this tumor eradication, the cellular components of
      spleen and regional lymph nodes, tumor infiltrating cells and antitumor effector
      cells were investigated. Pretreatment with NCS on day -3 caused an increase in
      the percentage of T-cell subsets, a decrease in the percentage of B-cells, Mac-1+
      cells and asialo GM1+ cells and a decrease of the total cell number in the
      spleen. These changes were observed before but not during the period of tumor
      regression and were also observed in non-transplanted mice with NCS treatment. In
      the lymph nodes, while B-cells increased on Meth A transplantation, this was
      suppressed by NCS pretreatment. Although histological examination of tumor
      nodules showed the presence of only a few host immune cells in the tumor tissue,
      the area of necrosis was already extensive on day 7 and expanded thereafter. In
      vivo depletion of whole T-cells, T-cell subsets or asialo GM1+ cells by antibody
      treatment suggests that the antitumor effector cells in tumor eradication were
      Thy1,2+/Lyt2+, and at least some of which also express asialo GM1 antigen and
      that L3T4+ T-cells were also involved in tumor eradication.

PMID- 9285250
TI  - Rationale for the introduction of long chain polyunsaturated fatty acids and for
      concomitant increase in the level of vitamin E in infant formulas.
AB  - There is significant scientific agreement that human milk is the best source of
      nutrients for the human infant. In addition it is also agreed that the
      constituents of human milk and their concentrations should form the basis of
      infant formula compositions. The objectives of this review are two fold: to
      examine the data on the long chain polyunsaturated fatty acid levels (LC-PUFA) in
      human milk and the rationale for inclusion of these lipids in infant formulas;
      secondly, as a consequence of addition of highly unsaturated lipids to infant
      formulas, the antioxidant requirements are increased. Therefore the effect of the
      addition of LC-PUFA on infant vitamin E status is also examined.

PMID- 9285251
TI  - Vitamin A requirements assessed by plasma response to supplementation during
      pregnancy.
AB  - Plasma vitamin A responses were examined in 30 low income pregnant women before
      and after supplementation with vitamin A. In the groups of women who had an
      initial (at < 20 weeks) plasma vitamin A of less than 30 micrograms/dl retinol,
      typical changes representing a peak at mid gestation and a significant decline at
      term were observed. Supplementation with vitamin A tablets equivalent to 1800
      micrograms of retinol daily for 12 weeks was able to raise the plasma vitamin A
      content at term. On the other hand, those women who had an initial plasma vitamin
      A concentration of more than 30 micrograms/dl did not show any appreciable
      changes even with vitamin A supplementation. Consistent beneficial effects of
      supplementation on maternal and cord vitamin A and maternal hemoglobin and
      progesterone were noted in our previous studies only when the supplementation
      lasted for 12 weeks and not after 10 weeks. Using these data with dietary intake
      obtained from other studies, an attempt was made to estimate the requirements of
      vitamin A during pregnancy. The approximate requirement of 780 retinol
      equivalents (RE) obtained, is in agreement with earlier recommendations of FAO
      and Indian Council of Medical Research (ICMR) Expert Committees, but is higher
      than the recent ICMR recommendations.

PMID- 9285252
TI  - Vitamin A and apoptosis in colonic tumor cells.
AB  - The mechanism by which vitamin A prevents or delays chemical carcinogenesis
      remains unclear. In addition to these antimutagenic and antiproliferative
      activities, vitamin A seems able to induce programmed cell death. In this study,
      we assess the suggested role of vitamin A on the in vitro apoptosis induction in
      a rat colonic tumor cell line. Several concentrations of retinyl palmitate were
      added in the culture media. We observed cell proliferation by measuring the
      (3H)thymidine incorporation, cell differentiation by measuring the intestinal
      alkaline phosphatase expression, and apoptosis induction by DNA fragmentation and
      morphological evolution of adherent and floating cells. The results show that
      vitamin A decreases (3H)thymidine incorporation after 1 day of treatment, induces
      alkaline phosphatase expression, and increases the number of cells falling in
      apoptosis. This report confirms the role of vitamin A on the induction of cell
      differentiation, on the inhibition of cell proliferation and shows the vitamin A
      capacity to induce apoptosis. These results could be attractive to prevent
      development of colon cancer by vitamin A supplemented diets.

PMID- 9285253
TI  - Interaction of vitamins E and K: effect of high dietary vitamin E on
      phylloquinone activity in chicks.
AB  - To determine the influence of vitamin E on phylloquinone activity, one day-old
      chicks were raised on a masch diet supplemented with different amounts of vitamin
      E for 31 days. In chicks fed a diet high in vitamin E (4000 mg allrac-alpha
      tocopheryl acetate/kg) but adequate in vitamin K (0.14 mg phylloquinone/kg) a
      threefold increase in prothrombin time and an increase in mortality rate (five
      out of twelve animals died from increased bleeding tendency) was observed. The
      inhibiting effect of high dietary vitamin E on procoagulant factors could be
      prevented by increasing dietary phylloquinone supplementation. Weight
      development, and feed utilization were insignificantly different in chicks fed
      different amounts and ratios of vitamins E and K1. Plasma and liver alpha
      tocopherol levels correlated with dietary amounts of vitamin E. Increased
      phylloquinone levels in the diet did not significantly influence alpha-tocopherol
      concentrations in plasma and liver, but coagulopathy caused by high vitamin E
      intake could be reversed.

PMID- 9285254
TI  - Dietary thiamin supply during gestation effects thiamin status of lactating rats
      and their suckling offspring.
AB  - This investigation was designed to examine the effect of dietary thiamin supply
      during gestation on body thiamin status of lactating rats and their suckling
      offspring, and thiamin in milk from 1 to 13 days postpartum. Therefore, a study
      over two generations was conducted feeding 2, 6.7 and 20 mg/kg thiamin during
      gestation and 8 mg/kg thiamin during lactation. Rat dams receiving inadequate
      thiamin during gestation and their offspring were thiamin-deficient on the basis
      of reduced activity of transketolase in blood and erythrocytes, which did not
      reach completely the control level even two weeks postpartum. The thiamin intake
      during gestation influenced significantly the thiamin levels in tissues of the
      dams and their offspring. However, the observed dose-dependence remained only for
      the first days of lactation. The thiamin concentration in milk two days
      postpartum also reflected the nutritional thiamin status from the pregnant rats,
      in which the thiamin concentration raised continuously with the duration of the
      lactation cycle. The data indicate that an adequate thiamin supply during
      lactation can not completely compensate for an inadequate thiamin supply during
      gestation, and that necessitates a constant thiamin intake.

PMID- 9285255
TI  - Vitamin C status of adults living in Valencia, Spain. Influence of non
      nutritional factors on plasma vitamin C.
AB  - Ascertaining the antioxidant nutritional status of different population groups is
      of great interest because of the probable benefits of these nutrients in the
      prevention of chronic disease. In this study the vitamin C status of adults
      living in a region characterized by its high availability of food with a high
      vitamin C content was investigated. In addition, vitamin C intake and the effect
      of non-nutritional factors on plasma vitamin C was examined. The majority of the
      subjects had an adequate vitamin C status. Nevertheless, by a probabilistic
      method it was established that a large proportion of the population was at risk
      of consuming inadequate amounts of vitamin C, the risk being considerably higher
      among male smokers. Females had higher vitamin C plasma concentrations than men.
      This difference persisted after adjusting the data for smoking habits. Also
      women's vitamin C intake was higher. Smoking affected male's plasma vitamin C
      concentrations negatively. Neither age nor the season of data collection had an
      effect on plasma vitamin C. Vitamin C intake was only influenced by season among
      males. No factor affected significantly vitamin C intake or plasma vitamin
      concentrations among females. Finally, multiple linear regression analysis showed
      that vitamin C intake and smoking habits make it possible to predict, in part,
      plasma vitamin C concentrations in males.

PMID- 9285256
TI  - Vitamin C status of patients with chronic renal failure, dialysis patients and
      patients after renal transplantation.
AB  - The vitamin C status of patients with chronic renal failure (CRF), dialysis
      patients (DP) and patients after renal transplantation (RT) was the object of
      this investigation. Levels of vitamin C intake from dietary records were
      estimated at mean values of 93.5 mg/d (CRF), 65.5 mg/d (DP) and 163.9 mg/d (RT).
      Compared to the recommendation of the German Society of Nutrition (75 mg/d), this
      indicated a normal range of supply for all groups except the group of DP. The
      corresponding mean plasma concentrations were 62.2 mumol/l (CRF), 80.3 mumol/l
      (DP) and 68.8 mumol/l (RT). Supplements of 60 or 100 mg vitamin C given to
      patients of the DP-group after each dialysis session showed slightly, but not
      significantly higher concentrations of vitamin C in plasma. During dialysis
      treatment, plasma vitamin C concentrations dropped to approximately 50% of the
      basal value, but almost reached initial levels again 44 hours later, both with
      and without supplementation. During one treatment period, vitamin C loss in the
      dialysate of three patients ranged between 92.5 and 333.6 mg. The amount of
      vitamin C in plasma, however, dropped to approximately 50% of the basal value for
      these patients, too.

PMID- 9285257
TI  - Assessment of serum antioxidant micronutrients and biochemical indicators of
      nutritional status in children with cancer in search of prognostic factors.
AB  - Serum vitamins A (retinol) and E (alpha-tocopherol), beta-carotene, zinc and
      selenium, and related proteins for 157 children with newly diagnosed and
      histologically proven malignancy were compared with those of 632 cancer-free
      controls. Incident cancer cases and controls were 1-16 years of age and recruited
      in 1986-1989. Age and sex-adjusted serum concentrations of beta-carotene and
      alpha-tocopherol were significantly inversely associated with cancer. No
      significant association with cancer was observed for serum values of selenium.
      Although low levels of antioxidants might in part be involved through a causality
      link, the reported decreased peripheral nutrient levels are considered rather as
      an impairment of the body's defence system, occurring during the cancer-related
      metabolic and nutritional disturbances and inflammation processes. The cancer
      cases group was followed-up and examined 6 months after diagnosis. Among the 157
      subjects, 24 had died and 133 were reported to be alive. No substantial
      difference for any antioxidant or chemistry variable at onset was observed as a
      function of clinical outcome and health status.

PMID- 9285258
TI  - Rapid incorporation of docosahexaenoic acid from dietary sources into brain
      microsomal, synaptosomal and mitochondrial membranes in adult mice.
AB  - This study examined the incorporation of docosahexaenoic acid (DHA) from several
      dietary sources into the brain tissue and intracellular organelles in mice which
      had been fed a 5% palm oil (low n-3 fatty acid level) diet for 8 or 11 weeks. The
      percentages of DHA in the tissues of mice fed 5% representative oils for 30 days
      or 5% purified n-3 fatty acid diets for 6 days were analyzed using gas
      chromatography. The percentage of DHA in the brain was ranked in the following
      order: the salmon oil diet group > the sardine oil diet group > > the perilla oil
      diet group > > the lard and palm oil diet groups for the 30 day feeding trial;
      and the DHA diet group > > the eicosapentaenoic acid and alpha-linolenic acid
      diet groups for the 6 day feeding trial. The percentage of arachidonic acid
      showed a more dramatic decrease than that of docosapentaenoic acid. These results
      reflected the plasma fatty acid concentrations, but were not as pronounced as the
      changes observed in the plasma. The majority of the DHA incorporated into the
      brain was recovered in microsomal, synaptosomal, and mitochondrial fractions
      separated by density gradient centrifugation. These membrane fractions took up
      DHA within several days. These results suggest that the intake of DHA itself
      increases the DHA level of brain membranes more rapidly than intake of the
      precursors in animals fed a low n-3 fatty acid level diet.

PMID- 9285259
TI  - Death themes in anorexia nervosa: dimensions for a reply to Jackson et al.
AB  - OBJECTIVE: To provide a critical, theoretical response to some ideas argued
      initially by Jackson and Davidson (Int J Eat Dis, 5, 821-835, 1986). Those ideas
      developed an understanding of anorexia nervosa in terms of disturbed death
      ideation and the notion of the anorexia nervosa sufferer as a "survivor." This
      paper was intended to broaden the frame of reference for a consideration of the
      relationship between eating disorders and death ideation. METHOD: The approach is
      a reflection on three domains of thinking about death and destructiveness, two
      within psychology, the third a perspective provided by philosophy. Specifically,
      early post-Freudian work, personal construct psychology, and the philosophical
      tradition that makes death generally significant in human life, that is,
      Existentialism, are discussed in terms of their illumination of the ideas under
      review. RESULTS: The result is a series of speculative observations that
      constitute an argument that these three domains together provide a strong
      countercritical position to the idea of a universal, even a general significance
      of death, particularly etiologically, in anorexia nervosa. DISCUSSION: The
      discussion suggests that the particular significance of death ideation in a
      multidimensional condition like anorexia nervosa must be derived in each
      particular case where it will sometimes be more, sometimes less significant, and,
      importantly, will mean something different to each individual sufferer.

PMID- 9285260
TI  - Femininity, masculinity, and disordered eating: a meta-analytic review.
AB  - OBJECTIVE: To understand the developmental psychopathology of eating disorders,
      it is crucial to explain the large gender discrepancy in the rates of these
      disorders, especially anorexia nervosa and bulimia nervosa. In this paper, meta
      analysis was used to examine the relationship between gender role adherence and
      the existence of eating problems. METHOD: Of the 69 studies examined, 22
      contained data deemed valid for the analyses. Measures of difference (d) and
      homogeneity were calculated. These studies used the Personal Attributes
      Questionnaire (PAQ) or the Bem Sex Role Inventory (BSRI) to measure gender role
      adherence. RESULTS: Findings indicated a small, heterogeneous positive
      relationship between femininity and eating problems and a small, heterogeneous
      negative relationship between masculinity and eating problems. Studies that used
      a clinical sample showed a larger discrepancy in masculinity scores between the
      eating-disordered and the control groups than did studies using surveys to
      identify eating problems. Six studies measured gender role traditionalism. The
      eating-disordered groups did not differ significantly on these measures compared
      to the control groups. DISCUSSION: Despite construct validity problems with the
      use of the PAQ and the BSRI in this area of study, data suggest that gender role
      is related to eating problems. Crucial aspects of femininity likely to be related
      to eating problems need to be operationalized and their link to eating disorders
      examined.

PMID- 9285261
TI  - The selectivity of inclusion and exclusion criteria in bulimia nervosa treatment
      studies.
AB  - OBJECTIVE: To examine the rates of exclusion and inclusion in various research
      studies for a series of 51 treatment-seeking patients. METHOD: The inclusion and
      exclusion criteria employed in a sample of 41 studies were applied to a series of
      51 treatment-seeking bulimia nervosa patients. RESULTS: Of the sample of 51, 11,
      (21.6%) would have been excluded from 16 (39%) of the studies because of an age
      greater than 30; 13 (32%) of the studies would have excluded 8 (16%) of our
      patients because of weight > 110% ideal body weight. Thirteen (26%) would have
      been excluded from 22 (54%) of the studies because of active psychotropic drug
      use, despite the lack of response. DISCUSSION: Some of the patients who may be
      most difficult to work with may be excluded from treatment studies.

PMID- 9285262
TI  - Psychiatric disorders in women with bulimia nervosa and their first-degree
      relatives: effects of comorbid substance dependence.
AB  - OBJECTIVE: Women with bulimia nervosa (BN) and comorbid substance dependence
      often display impulsive behaviors. We assessed Axis I and II psychiatric
      diagnoses in their first-degree relatives in order to understand the etiological
      factors that may contribute to this subtype of BN. METHOD: We used contemporary
      family-epidemiological methodology to compare the lifetime prevalence of
      psychiatric disorders among 47 women with BN and 44 non-eating-disordered
      community control women, and their first-degree relatives (177 and 190,
      respectively). BN probands were stratified by the presence (n = 20) or absence (n
      = 27) of a lifetime history of alcohol and/or drug dependence. RESULTS: Social
      phobia, conduct disorder, and clusters B and C personality disorders were
      significantly more prevalent among BN probands with substance dependence than
      among BN probands without substance dependence or control women probands.
      Substance use disorders, social phobia, panic disorder, and cluster B personality
      disorders were significantly more prevalent among the relatives of BN probands
      with substance dependence than the relatives of the other two groups. DISCUSSION:
      Women with BN and substance dependence have problems with social anxiety,
      antisocial behavior, and a variety of personality disturbances, and come from
      families where there are problems with substance use disorders, anxiety,
      impulsivity, and affective instability. These data raise the possibility that a
      familial vulnerability for impulsivity and affective instability may contribute
      to the development of substance dependence in a subgroup of women with BN.

PMID- 9285263
TI  - The incidence of parental obesity in overweight individuals.
AB  - OBJECTIVE: The purpose of this study was to ascertain the incidence of parental
      obesity in overweight individuals. METHOD: The records of 3,227 adult (age 18 or
      older) obese (body mass index [BMI] higher than 27) outpatients seen at the
      Cathedral Hill Obesity Clinic over the past approximate three decades were
      reviewed. The incidence of parental and grandparental obesity was determined from
      patient histories. RESULTS: A far higher prevalence of obese female parents than
      obese male parents was found in this overweight population. This excess is
      greater in blacks than in whites, and in females than in males. BMI is greater in
      earlier than later age of obesity onset. A higher incidence of obese grandmothers
      than grandfathers was also found in this sample. DISCUSSION: The findings of a
      higher maternal and grandmaternal obesity incidence are discussed in terms of
      environmental and genetic factors.

PMID- 9285264
TI  - Overt and covert sexual abuse: relationship to body image and eating disturbance.
AB  - OBJECTIVE: To separate forms of overt and covert sexual abuse and assess their
      independent contribution to the development of body image and eating disturbance.
      METHOD: A new measure was developed--the Covert-Overt Sexual Abuse Questionnaire
      (COSAQ)--and correlated with levels of body image, eating disturbance, social
      desirability, self-esteem, and depression. RESULTS: Factor analyses on three
      independent samples yielded two distinct subscales which were labelled Overt and
      Covert. Each scale had excellent internal consistency and test-retest
      reliability. Regression analyses demonstrated the ability of the Covert factor to
      explain variance associated with body image disturbance and eating dysfunction
      beyond that accounted for by levels of social desirability, self-esteem,
      depression, and overt sexual abuse. DISCUSSION: These findings support the
      importance of a more "subtle" form of early trauma--covert sexual abuse--in the
      development of body image and eating-related problems.

PMID- 9285265
TI  - Effects of suppressing thoughts about body weight: a comparison of dieters and
      nondieters.
AB  - OBJECTIVE: Experimental suppression of a neutral target thought often results in
      a subsequent "rebound" in the frequency of the thought. In this study, we tested
      the hypothesis that suppression of weight-related thoughts contributes to body
      weight preoccupations characteristic of dieters. METHOD: Subjects included 19
      female dieters and 21 female nondieters. Following a randomized design, subjects
      were asked either to suppress (experimental condition) or express (control
      condition) the thought of weighing themselves. RESULTS: Nondieters demonstrated a
      significant rebound in frequency of the target thought following suppression (p <
      .05). Dieters expressed weight-related thoughts more frequently than nondieters,
      but did not show a rebound following target thought suppression. DISCUSSION:
      Thought suppression may foster development of weight-related preoccupations
      whereas the role suppression plays in the maintenance of dieters' weight-related
      preoccupations remains unclear.

PMID- 9285266
TI  - Subjective or objective binge: is the distinction valid?
AB  - OBJECTIVE: The aim of this study was to examine the validity of the distinction
      between objective and subjective binge episodes. METHOD: Data were analyzed from
      101 women who received 12 weeks of cognitive-behavioral therapy (CBT) for binge
      eating in a previous treatment study. Binges recorded by participants on daily
      food records were rated as either subjective or objective according to the Eating
      Disorder Examination rating guidelines. Unpaired t tests were performed to
      determine the relationship between type of binge, psychopathology, and other
      descriptive measures, including response to treatment. RESULTS: These analyses
      revealed no significant differences between types of binge episodes. Of note is
      the observation that objective binge episodes appeared to decrease more rapidly
      than subjective episodes during treatment. DISCUSSION: Future research should
      continue to investigate whether "large amount of food" is an appropriate
      criterion for the diagnosis of binge eating.

PMID- 9285267
TI  - Cognitive avoidance of threat cues: association with Eating Disorder Inventory
      scores among a non-eating-disordered population.
AB  - OBJECTIVE: This two-part study investigated the cognitive processing of food- and
      threat-related information in a non-eating-disordered population, particularly
      exploring the mechanisms that might explain the process of cognitive avoidance
      among women with bulimic attitudes. METHOD: In the first study, 30 female
      students solved anagrams of neutral, food, and threat words. In the second study,
      50 male and female students solved anagrams of words reflecting physical threat,
      self-directed ego threat, and ego threat directed from others. RESULTS: In this
      task, there was no association between slower processing of threats and eating
      characteristics, but there were associations with Eating Disorders Inventory
      (EDI) scales that reflect "ego development." DISCUSSION: The most reliable
      evidence of cognitive avoidance was among those participants who show the ego
      development characteristics that have been identified as important in the
      development and etiology of eating psychopathology. The implications for models
      of eating psychopathology and their treatment are discussed.

PMID- 9285268
TI  - A comparison of subgroups of inpatients with anorexia nervosa.
AB  - OBJECTIVE: Classification of subgroups of people with anorexia nervosa has been
      in flux. It has not been clear whether anorexics who only purge should be grouped
      with pure restricters or with people who both binge and purge. METHODS: We
      compared 27 restricting-type anorexics (RAN), 26 bulimic anorexics (BAN), and 34
      restricting anorexics with purging behaviors (RAN-P). All subjects were
      underweight and recently admitted to a hospital. We excluded subjects who had not
      had a diagnosis of anorexia nervosa for at least 1 year duration. RESULTS: The
      three groups of subjects had similar scores for Depression and Anxiety on the
      Beck Depression Inventory, the Spielberger State and Trait Anxiety Inventory, and
      on the EDI subscales aside from higher scores for BAN subjects on the Bulimia
      subscale. DISCUSSION: These three subgroups of anorexia nervosa have similar
      degrees of dysphoric moods and core eating disorder symptoms when underweight and
      malnourished.

PMID- 9285269
TI  - Ethnic differences in psychosocial and health behavior correlates of dieting,
      purging, and binge eating in a population-based sample of adolescent females.
AB  - OBJECTIVE: To examine ethnic differences in factors associated with disordered
      eating behaviors. METHOD: Data were collected from 17,159 adolescent females who
      completed a school-based health survey conducted in 1987. RESULTS: In all ethnic
      groups, dieting was associated in bivariate analyses with weight dissatisfaction,
      perceived overweight, and low body pride. Purging was associated with weight
      dissatisfaction, perceived overweight, low body pride, greater suicide risk, and
      greater alcohol use. Binge eating was associated with weight dissatisfaction,
      perceived overweight, low body pride, lower family connectedness, greater peer
      acceptance concerns, and emotional stress. DISCUSSION: Body dissatisfaction and
      perceived overweight are consistent correlates of dieting and binge eating in
      adolescent females of diverse ethnic groups. Ethnic subculture does not appear to
      protect against the broader sociocultural factors that foster body
      dissatisfaction among adolescent females. Implications for understanding
      sociocultural influences on dieting, obesity, and eating disorders are discussed.

PMID- 9285270
TI  - The prevalence and correlates of binge eating in a British community sample of
      women with a history of obesity.
AB  - OBJECTIVE: To estimate the frequency of binge eating and binge eating disorder
      and their correlates in a sample of women with a history of obesity. METHOD: A
      group of women who had been found in a previous community study to have a body
      mass index > or = 30 were studied using self-report measures (n = 74) and
      interview (n = 62). RESULTS: One subject met criteria for binge eating disorder,
      while 24% reported binging. Subjects who reported binging were significantly more
      likely to have a past history of depressive illness. DISCUSSION: Prevalence of
      binge eating, binge eating disorder, and psychopathology was broadly in keeping
      with that found in North America. In addition, there were nonsignificant trends
      towards a positive family history of obesity, of childhood obesity, of early
      onset of dieting, of excessive concern about weight and shape, and a recent
      history of weight reduction. Further study is required to elucidate the causes of
      binge eating in the obese.

PMID- 9285271
TI  - Selective processing of eating disorder relevant stimuli: does the Stroop Test
      provide an objective measure of bulimia nervosa?
AB  - OBJECTIVE: To evaluate the specificity of the modified Stroop test as an
      objective measure of bulimia nervosa. METHOD: A modified Stroop Test was
      administered to patients with bulimia nervosa and two non-clinical control groups
      of restrained and unrestrained eaters. RESULTS: The data failed to show any
      specificity in the Stroop effect. Nor did the test provide a useful measure of
      treatment response. DISCUSSION: Taken in conjunction with previous inconsistent
      findings, the results of this study call into question the utility of the
      modified Stroop effect as a specific measure of bulimia nervosa.

PMID- 9285272
TI  - Bilateral foot-drop in a patient with anorexia nervosa.
AB  - We report the occurrence of bilateral foot-drop in a patient with anorexia
      nervosa. To the best of our knowledge this has not been reported previously. The
      underlying pathology was found to be peroneal nerve palsy probably related to
      mechanical pressure at the head of the fibula. Nutritional deficiency may also be
      implicated.

PMID- 9285273
TI  - A slippery slope: economists and social insurance in the United States.
AB  - Since the 1980s welfare state protections have been blamed for a host of economic
      problems. In the United States, conservatives have always disliked Social
      Security but could not effectively attack this popular program until the 1980s,
      when they devised a new tactic--warning young people that they would never get
      their "money's worth" from Social Security, which is on the brink of
      "bankruptcy." The political climate, dominated by a drive to cut back "big
      government," also became favorable for attempts to destabilize Social Security
      politically. Thus, negative images of Social Security have been forced onto the
      public agenda, and economists who consider themselves "liberal" have uncritically
      accepted this new set of political "givens." It is an example of how they address
      "crises" as separable issues tied to no particular social context.

PMID- 9285274
TI  - The logic of tax-based financing for health care.
AB  - Employment-based health insurance faces serious problems. For the first time, the
      number of Americans covered by such health insurance is falling. Employers
      strongly oppose the employer mandate approach to extending health insurance.
      Employment-based financing is regressive and complex. Serious debate is needed on
      an alternative solution to financing health care for all Americans. Taxation
      represents a clear alternative to employment-based health care financing. The
      major criterion for choosing a tax is equity, with simplicity a second criterion.
      An earmarked, progressive individual income tax is a fair and potentially simple
      tax with which to finance health care. The political feasibility of such a tax is
      greater than that of employer mandate legislation.

PMID- 9285275
TI  - Devolution and aging policy: racing to the bottom in long-term care.
AB  - For two decades, New Federalism, devolution, and other challenges to the federal
      role in domestic health and human services policy have fundamentally shaped the
      structure and delivery of long-term care in the United States. Devolution evokes
      crucial questions concerning the future of universal entitlement programs such as
      Social Security and Medicare and, with them, the future of aging and long-term
      care policy. This article examines the implications of the "devolution
      revolution" for long-term care in the context of the sociodemographics of aging
      and the managed care movement. Central issues are the extent to which state-level
      discretionary policy options (1) alter priorities, services, and benefits for the
      elderly and disabled: (2) foster a race to the bottom in long-term care; (3)
      promote generational, gender, racial and ethnic, and social class trade-offs; and
      (4) fundamentally alter the role and capacity of nonprofit sector services that
      comprise a significant part of the long-term care continuum.

PMID- 9285276
TI  - Equity and distributive justice in European health care reform.
AB  - Equity is a central objective of most European health care systems, yet equity,
      particularly in the form of distributive justice, has not been a central
      objective of many recent health sector reforms. This article considers three
      aspects of the relationship between equity and recent health reforms. After
      defining what is meant by equity in the health sector, the author briefly
      examines available evidence on present levels of equality then discusses the
      equity implications of ongoing reforms in European health care systems.

PMID- 9285277
TI  - Star wars and strategic defense initiatives: work activity and health symptoms of
      unionized bank tellers during work reorganization.
AB  - Work activity and health symptoms of bank tellers whose work was undergoing
      reorganization were examined during a university-union study of the health
      effects of work in women's traditional jobs. Data were gathered through
      collective and individual interviews, analysis of work activity, and a
      questionnaire administered to 305 tellers. Employees worked in a standing posture
      over 80 percent of the time. More than two-thirds frequently suffered pain in
      back, legs, and feet. The average teller had been involved in 3.7 robberies as a
      direct victim and six as a witness. Work required feats of memory and
      concentration. In order to meet job demands, tellers engaged in supportive
      activities and teamwork. The introduction of individualized objectives threatened
      the employees' ability to collaborate and induced distress. More than twice as
      many tellers as other female workers in Quebec experience psychological distress
      (Ilfeld scale), related to: robbery during the past two years (odds ratio = 1.7;
      confidence interval = 1.0-2.9); difficult relations with superiors (O.R. = 2.6;
      C.I. = 1.3-5.3); and full-time work (O.R. = 2.3; C.I. = 1.3-3.9). Diverse methods
      enriched the analysis, and union participation allowed the proposal of concrete
      correction measures.

PMID- 9285278
TI  - Working conditions in home care: negotiating race and class boundaries in
      gendered work.
AB  - Home care work in metropolitan areas is a source of employment for immigrant
      women of color. Service work of this type intertwines domestic and caring labor
      in ways that reinforce the historically gendered and racialized nature of the
      work. Such macro level economic and political issues are played out at the micro
      level of daily service provided within elderly clients' homes. A study of these
      processes in home care work was carried out in urban southern Ontario in two
      nonprofit home care agencies. In-depth interviews and focus groups held with
      visible minority home care workers suggested that workers deal daily with racist
      attitudes and behaviors from clients and their families; agencies recognize these
      oppressive processes but usually handle them on a case-by-case basis through
      supervisors; and home care workers handle racism on the job as they do in their
      off-work hours-by avoidance, situating incidents within an analysis of the
      circumstances of elderly clients, setting boundaries on discussions, and
      occasionally, confrontation.

PMID- 9285279
TI  - The politics of reproductive hazards in the workplace: class, gender, and the
      history of occupational lead exposure.
AB  - Over the past two decades, several U.S. companies have sought to bar women from
      jobs that expose them to potential reproductive hazards, justifying these
      exclusionary policies by their professed concerns for the well-being of unborn
      children and potential liability. Although recent court cases have stimulated
      academic interest in this issue, a historical review of the public health and
      medical literature reveals that this debate is not new. To understand the logic
      behind the emergence of "fetal protection" policies, one must examine the
      scientific history of occupational teratogens and the socio-political and
      economic forces that have driven scientific research in this field. Using lead as
      an example, the author argues that research on the reproductive hazards of
      employment has historically emphasized the risks to women and downplayed the
      risks to men. This results in environmental health policies that do not uphold
      the ultimate goal of occupational safety for all workers, but rather reinforce
      the systemic segregation of men and women in the workplace. Although the
      political struggle over exclusionary policies has a feminist orientation, it also
      has important class dimensions and ultimately must be viewed within the broader
      context of American capitalist production.

PMID- 9285280
TI  - Population control I: Birth of an ideology.
AB  - Population control, as a major international development strategy, is a
      relatively recent phenomenon. However, its origins reach back to social currents
      in the 19th and early 20th centuries, culminating in an organized birth control
      movement in Europe and the United States. The conflicts and contradictions in
      that movement's history presage many of today's debates over population policy
      and women's rights. Eugenics had a deep influence on the U.S. birth control
      movement in the first half of the 20th century. After World War II private
      agencies and foundations played an important role in legitimizing population
      control as a way to secure Western control over Third World resources and stem
      political instability. In the late 1960s the U.S. government became a major
      funder of population control programs overseas and built multilateral support
      through establishment of the U.N. Fund for Population Activities. At the 1974
      World Population Conference, Third World governments challenged the primacy of
      population control. While their critique led population agencies to change their
      strategies, population control remained a central component of international
      development and national security policies in the United States.

PMID- 9285281
TI  - Population control II: The population establishment today.
AB  - Although population assistance represents a relatively small share of official
      development assistance, it influences many other aspects of development planning.
      The organizations that comprise the population establishment have a common
      purpose--the reduction of population growth in the Third World--but they are not
      homogeneous and sometimes have conflicting goals and strategies. National
      governments, multilateral agencies, nongovernmental organizations, foundations,
      academic centers, and pressure groups all contribute to creating and sustaining
      what has become a virtual population control industry. Through scholarships,
      travel grants, awards, and favorable publicity, Third World elites have been
      encouraged to join the population establishment. The World Bank, the U.S. Agency
      for International Development, and the U.N. Fund for Population Activities have
      pursued explicit strategies for pressuring Third World governments to design and
      implement population policies, most recently in Africa.

PMID- 9285282
TI  - Overdramatization of the burdens on health and social services: a continuing
      debate in the history of German medicine.
AB  - Departing from the latest academic research into Nazi medicine in Germany, the
      author looks at theoretical and ideological concepts in German history that left
      their mark on the formation of race hygiene. He argues that the overdramatization
      of the economic burden caused by the special requirements of the chronically ill
      and handicapped runs through all epochs of modern medical history and that this
      culturally pessimistic way of looking at a serious social problem in Germany
      reveals a frightening tradition which reached its cruelest climax in the so
      called T4 operation of the Nazis. The author makes a plea for this dark chapter
      of German medical history to be carefully analyzed and for the results of this
      research to be used in the current discussion on the further development of the
      health system, particularly in regard to patients who require special care.

PMID- 9285283
TI  - Lesions of the posterior insular cortex impair water maze performance in the rat.
AB  - Performance of rats in the Morris water maze was measured after small excitotoxic
      lesions were produced bilaterally in two areas in the insular cortex, 0.3 and 2.3
      mm posterior to bregma in the upper bank of the rhinal sulcus. The rats were
      trained and tested in two successive days to find an underwater platform.
      Compared to intact animals groups with lesions at AP-0.3 and AP-2.3 were impaired
      as measured by latency. These animals also did not prefer the correct quadrant
      while searching for the platform. There were no differences between the groups in
      percentage of time spent in periphery and speed of swimming. The results do not
      support the hypothesis that the destruction of an autonomic center at AP-0.3 will
      impair performance while the destruction of a more posterior part of the insular
      cortex will not, and are interpreted as further evidence for multifactor
      sensitivity of the water maze task.

PMID- 9285284
TI  - Expression of glutamate receptor subunit 1 and nitric oxide synthase in the
      hypoglossal nucleus and dorsal vagal nucleus in the rat after neurectomy.
AB  - Using nitric oxide synthase (NOS) and glutamate receptor subunit 1 (GluR1)
      immunohistochemistry, the present study demonstrated changes in the expression of
      NOS and GluR1 in the hypoglossal (HN) and dorsal vagal nucleus (DVN) after
      neurectomy. Two and 7 days after sectioning the left hypoglossal nerve, NOS
      expression was seen in a few neurons but GluR1 immunoreactivity was drastically
      reduced in the ipsilateral HN. The upregulation of NOS immunoreactivity in the HN
      appeared to peak at 14 days postoperation (dpo). At this period, however, the
      GluR1 immunoreactivity almost completely disappeared. Twenty-one, 35 and 56 days
      after neurectomy, NOS immunoreactivity was still expressed in the ipsilateral HN;
      at the same time, GluR1 immunoreactivity reappeared in a few neurons of the
      nucleus. Ninety days after operation, NOS immunoreactivity completely disappeared
      on the operated side of the nucleus, but GluR1 immunoreactivity was re-expressed
      in many hypoglossal neurons. The number of such neurons was obviously less than
      that on the unoperated side. After sectioning the left vagus nerve in the same
      animals, the expression of NOS immunoreactivity in the ipsilateral DVN resembled
      that in the HN. On the unoperated side, NOS immunoreactivity was demonstrated in
      some neurons in the DVN, like that in the normal. In both normal and operated
      rats, only a few neurons expressed GluR1 immunoreactive products on both the
      operated and unoperated sides of the DVN. Combining with previous results on
      protein synthesis observed at 14 dpo, the present investigation suggested that in
      the early stages after neurectomy, the expression of NOS immunoreactivity and
      loss of GluR1 expression in the HN may indicate the organism's double protective
      mechanism. Lastly, the reappearance of GluR1 in the same nucleus from 21 to 90
      days after operation may reflect functional recovery of the hypoglossal neurons.

PMID- 9285286
TI  - Motor programs of spontaneous and visually guided saccades in macaque monkey: an
      electrophysiological approach.
AB  - The discharge activity of 37 burst neurons in the paramedian pontine reticular
      formation and the saccades performed in the dark (spontaneous saccades) and
      between visual targets (attentive visually guided) were recorded in two macaque
      monkeys. Forty-five % of spontaneous saccades showed more than one maximum of
      velocity (irregular velocity profiles), while visually guided saccades were
      always characterized by a single maximum of velocity (regular velocity profiles).
      The discharge pattern of each burst neuron (short lead neuron) was different
      according to the saccade velocity profile. We observed a clear inhibition within
      the burst neuron discharge for irregular velocity profiles, thus giving rise to
      multiple maxima of discharge frequency, and to a clearly interrupted saccade. The
      same neuron showed only one maximum of discharge frequency for regular saccades.
      Then the hypothesis of two different neural networks generating the different
      motor programs of spontaneous and attentive visual guided saccades is put forward
      and discussed.

PMID- 9285285
TI  - Effects of low-frequency magnetic fields on electrocortical activity in humans: a
      sferics simulation study.
AB  - A previously recorded electromagnetic impulse of natural origin, a 10 kHz-sferic,
      was simulated and presented to 20 subjects. The magnetic component of the signal
      with a maximum field amplitude of 50 nT and a duration of 500 microseconds was
      applied over a duration of 10 minutes with a pulse repetition rate that varied
      statistically between 7 and 20 Hz. After sferics exposure, an additional 20
      minutes without treatment were recorded in order to examine possible prolonged
      effects of sferics stimulation. The control group (n = 20) received no treatment.
      As a dependent measure, electrocortical changes throughout the course of the
      experiment were determined by means of EEG spectral analysis and compared between
      the two groups. Sferics exposure provoked increases in alpha and beta power. The
      effect was present during stimulation and continued for 10 minutes after the end
      of treatment. A longer lasting influence of sferics exposure was displayed by
      subjects with a high degree in weather sensitivity, somatic complaints, and
      neuroticism, who continued to stay on an enhanced alpha power level until the end
      of registration (20 minutes after the end of exposure). With these results a
      general electrocortical sensitivity towards sferics as well as individual
      differences in sferics reactivity could be demonstrated.

PMID- 9285287
TI  - The physiological responses induced by superficial acupuncture: a comparative
      study of acupuncture stimulation during exhalation phase and continuous
      stimulation.
AB  - This study investigated the physiological effect of superficial acupuncture
      stimulation during a patient's exhalation phase in a sitting position (SES). The
      response to SES was compared to the stimulation applied continuously without
      considering the respiratory phase (CONT). It evaluated a chronic tension-type
      headache patient's static electromyographic (EMG) activity, pain response, heart
      rate, pulse height, and skin conductance level. The results indicated that SES
      stimulation significantly decreased headache intensity and demonstrated a strong
      trend towards decreasing static EMG activity compared to CONT stimulation. The
      study concluded that acupuncture, applied on the same point and at the same
      depth, produced different physiological effects, depending on whether the
      stimulation was applied during exhalation only or continuously applied. This
      suggests that the effect of acupuncture derives not only from point selection
      matching symptoms, but also from a consideration and utilization of the patient's
      respiratory phase during stimulation.

PMID- 9285288
TI  - Immediate recovery of cognitive functions and resolution of fatigue by treatment
      with weak electromagnetic fields in a patient with multiple sclerosis.
AB  - Cognitive deficits are common among patients with multiple sclerosis (MS). The
      pathogenetic mechanisms underlying the cognitive impairment in MS are unknown and
      there is presently no effective therapeutic modality which has shown efficacy in
      improving cognitive deficits in MS. A 53 year old college professor with a long
      history of secondary progressive MS experienced, over the preceding year,
      noticeable deterioration in cognitive functions with difficulties in short and
      long term memory, word finding in spontaneous speech, attention and concentration
      span. Unable to pursue his academic activities, he was considering early
      retirement. Mental examination disclosed features of subcortical and cortical
      dementia involving frontal lobe, left hemispheric and right hemispheric
      dysfunction. Almost immediately following the extracerebral application of AC
      pulsed electromagnetic fields (EMFs) of 7.5 picotesla intensity and a 4-Hz
      sinusoidal wave, the patient experienced a heightend sense of well being, which
      he defined as enhancement of cognitive functions with a feeling "like a cloud
      lifted off my head." He reported heightend clarity of thinking and during the
      application of EMFs he felt that words were formed faster and he experienced no
      difficulty finding the appropriate words. His speech was stronger and well
      modulated and he felt "energized" with resolution of his fatigue. There was
      improvement in manual dexterity and handwriting and testing of constructional
      praxis demonstrated improvement in visuospatial, visuoperceptive and visuomotor
      functions. It is suggested that some of the cognitive deficits associated with
      MS, which are caused by synaptic disruption of neurotransmitter functions, may be
      reversed through pulsed applications of picotesla range EMFs.

PMID- 9285289
TI  - Treatment with weak electromagnetic fields restores dream recall in a
      parkinsonian patient.
AB  - Absent or markedly reduced REM sleep with cessation of dream recall has been
      documented in numerous neurological disorders associated with subcortical
      dementia including Parkinson's disease, progressive supranuclear palsy and
      Huntington's chorea. This report concerns a 69 year old Parkinsonian patient who
      experienced complete cessation of dreaming since the onset of motor disability 13
      years ago. Long term treatment with levodopa and dopamine (DA) receptor agonists
      (bromocriptine and pergolide mesylate) did not affect dream recall. However,
      dreaming was restored after the patient received three treatment sessions with AC
      pulsed picotesla range electromagnetic fields (EMFs) applied extracranially over
      three successive days. Six months later, during which time the patient received 3
      additional treatment sessions with EMFs, he reported dreaming vividly with
      intense colored visual imagery almost every night with some of the dreams having
      sexual content. In addition, he began to experience hypnagogic imagery prior to
      the onset of sleep. Cessation of dream recall has been associated with right
      hemispheric dysfunction and its restoration by treatment with EMFs points to
      right hemispheric activation, which is supported by improvement in this patient's
      visual memory known to be subserved by the right temporal lobe. Moreover, since
      DA neurons activate REM sleep mechanisms and facilitate dream recall, it appears
      that application of EMFs enhanced DA activity in the mesolimbic system which has
      been implicated in dream recall. Also, since administration of pineal melatonin
      has been reported to induce vivid dreams with intense colored visual imagery in
      normal subjects and narcoleptic patients, it is suggested that enhanced nocturnal
      melatonin secretion was associated with restoration of dream recall in this
      patient. These findings demonstrate that unlike chronic levodopa therapy,
      intermittent pulsed applications of AC picotesla EMFs may induce in Parkinsonism
      reactivation of reticular-limbic-pineal systems involved in the generation of
      dreaming.

PMID- 9285290
TI  - Effect of physostigmine and verapamil on active avoidance in an experimental
      model of Alzheimer's disease.
AB  - The present study was performed to investigate and compare the effect of
      acetylcholinesterase inhibitor, physostigmine (0.045, 0.060 and 0.075 mg/kg sc,
      30 min before the tests) and Ca-antagonist, verapamil (1.0, 2.5, 5.0 and 10.0
      mg/kg sc, 30 min before the tests), on two-way active avoidance (AA) learning
      (acquisition and performance) in nucleus basalis magnocellularis (NBM)-lesioned
      rats. Bilateral electrolytic lesions of NBM induced significant decrease of
      acquisition and performance of AA responses in rats. Physostigmine (0.060 mg/kg)
      significantly improved only acquisition of AA, while verapamil (2.5 and 5.0
      mg/kg) significantly improved both type of AA behavior in NBM-lesioned rats.
      These results suggest that altered calcium homeostasis might play significant
      role in pathogenesis of experimental induced Alzheimer's disease (AD) and that
      administration of calcium antagonist such as verapamil might successfully
      ameliorate disturbances of learning and memory appeared after lesions of NBM.

PMID- 9285291
TI  - Magnetohydrodynamic wave resonance and the evocation of epileptiform activity by
      millitesla DC magnetic fields.
AB  - DC magnetic fields of low- to medium-flux density (nTesla to mTesla) affect a
      variety of brain activities. The cellular mechanism underlying these effects is
      unknown. A model involving magnetohydrodynamic waves and corresponding resonance
      phenomena is offered here as a solution. The model is discussed in relation to
      the evocation of epileptiform activity due to external DC magnetic fields in the
      mTesla range. The assumed existence of a resonance wave makes it possible to
      calculate the size of the involved area.

PMID- 9285292
TI  - Middle latency auditory evoked potentials in congenitally blind and normal
      sighted subjects.
AB  - Middle latency auditory evoked potentials were recorded in two groups of ten
      subjects each, viz, congenitally blind (CB) and age-matched subjects with normal
      vision (NV). The age range for both groups was 13 to 16 years. The CB group
      subjects had peripheral deficits, with absence of visual evoked responses. The
      peak latency of the Nb wave (the maximum negativity between 38 and 48 ms) was
      significantly lower in the CB group compared to NV group (p < .05, one-tailed,
      two factor ANOVA, Tukey test). In addition to these recordings from the vertex,
      recordings were also made from occipital areas, to test whether the visual cortex
      contributes to information processing at primary auditory cortical levels in the
      blind, as was reported in earlier studies on the generation of potentials during
      auditory selective attention. No such effect was observed. Hence, it appears that
      in blind subjects changes in generators of auditory middle latency evoked
      potentials are mainly related to latency, rather than to scalp distribution of
      these components.

PMID- 9285293
TI  - Memory deficits and industrial toxicant exposure: a comparative study of hard
      metal, solvent and asbestos workers.
AB  - Memory functioning was examined in ex-factory workers with hard metal disease,
      resulting from exposure to alloys utilizing cobalt. Since these workers are also
      exposed to organic solvents and may suffer from chronic hypoxia as a result of
      their pulmonary disorder, solvent and asbestos workers, as well as an unexposed
      matched sample, served as controls. Results demonstrated deficits in the
      allocation of attentional resources and in short-term verbal memory. A pattern of
      findings across several tests suggested that repetition or delay is important for
      adequate memory performance in individuals exposed to hard metal, implicating a
      deficit in encoding or slowed consolidation.

PMID- 9285294
TI  - Influence of the pineal gland on the expression of experimental allergic
      encephalomyelitis: possible relationship to the aquisition of multiple sclerosis.
AB  - Experimental allergic encephalomyelitis (EAE), a T-cell mediated autoimmune
      disease, is widely considered as an animal model of multiple sclerosis (MS). It
      is believed that breakdown of the blood brain barrier (BBB) reflects the initial
      mechanism in the induction of EAE. It has been reported that while neonatally
      pinealectomized Wistar rats develop extensive pathological changes and severe
      neurologic deficits upon induction of EAE with allogeneic spinal cord in
      adjuvant, adult rats pinealectomized at 6 weeks of age appeared resistant to the
      induction of EAE. These findings suggest that: (a) the pineal gland influences
      the expression of EAE and, by inference, the integrity of the BBB; and (b) there
      is an age-related window of susceptibility to the development of EAE possibly
      related to the level of maturation of the pineal gland and functional integrity
      of the BBB. This age-related susceptibility to the development of EAE in rats may
      be relevant to the timing of aquisition of MS where a viral infection in
      childhood is thought to initiate the induction of autosensitization to myelin
      antigens. More specifically, it is suggested that the viral infection associated
      with the development of MS most likely is acquired in infancy prior to the
      establishment of the melatonin circadian rhythms between 3 and 9 months of age.

PMID- 9285295
TI  - IFN-beta 1b treatment of relapsing multiple sclerosis has no effect on CD3
      induced inflammatory or counterregulatory anti-inflammatory cytokine secretion ex
      vivo after nine months.
AB  - Multiple sclerosis (MS) is presumed to be a T-cell mediated chronic inflammatory
      disease of the central nervous system. We have previously reported that IFN-beta
      1b (Betaseron) decreases CD3-mediated TNF-alpha secretion but increases another
      inflammatory cytokine, IL-6 after three months of treatment. We have now examined
      cytokine secretion of peripheral blood mononuclear (PMNC) cells after stimulation
      with OKT3 (anti-CD3) monoclonal antibody (mAb) or Con A in subjects with
      clinically stable relapsing MS before and three, six and nine months after
      initiating IFN-beta 1b treatment. At nine months Con A-induced TNF-alpha
      secretion decreased significantly below baseline but IFN-gamma secretion
      increased above baseline. There were no significant changes in Con A-induced IL-4
      over the six month period and no changes in IL-10 and IL-2 over the nine month
      period. After nine months on treatment the CD3-induced TNF-alpha and IFN-gamma
      secretion was not significantly different from the original baseline values.
      Increased CD3-mediated IL-6 secretion in on-treatment compared to pre-treatment
      samples at three months gradually declined to baseline values by nine months on
      treatment. There was no significant changes from baseline compared to nine months
      on-treatment in CD3-mediated IL-2, IL-4, IL-10. IFN-beta 1b (Betaseron) treatment
      has no clear persistent effect on CD3-induced inflammatory or counterregulatory
      anti-inflammatory cytokine secretion.

PMID- 9285296
TI  - Chronopharmacological studies on potassium citrate treatment of oxalocalcic
      urolithiasis.
AB  - The effect of minimum doses of extradietary potassium citrate ingestion on
      urolithogenic parameters has been studied. Separate urine fractions were
      collected in 24-hour periods. Five calcium oxalate stone formers have
      participated in the study. pH, calcium, citric acid, and the crystallization
      inhibitory capacity levels in fractional urine samples were determined before and
      during treatment. The most beneficial effect (increase in citraturia and
      crystallization inhibitory capacity) was produced by potassium citrate tablets
      ingested after dinner.

PMID- 9285297
TI  - Treatment of ureteral and renal stones by electrohydraulic lithotripsy.
AB  - Manipulation of ureteral and renal calculi can be done under direct vision using
      a fiberscope with increased safety and efficacy. We treated 207 ureteral and
      renal stones in 198 patients using electrohydraulic lithotriptor combined with
      transurethral fiberscope from July 1985 till January 1991. Electrohydraulic
      lithotripsy (EHL) successfully fragmented 187 out of 207 stones (90.3%). A total
      of 119 patients (57.5%) became stone-free 3 months after operation, which
      increased to 170 cases (82.1%) at a mean follow-up of 20 months. There were 6
      ureteral perforations (4 due to fiberscope and 2 due to EHL spark damage to the
      ureteral mucosa), which were treated immediately by open operation (2.9%). In 7
      cases (3.4%), the stone could not be fragmented due to its hardness. We believe
      electrohydraulic lithotropsy treatment combined with transurethral fiberscopy is
      a safe, effective, noninvasive and economical method for the treatment of urinary
      tract stones.

PMID- 9285298
TI  - Stone disintegration: effect of shock wave projection and electrode age on this
      parameter in a standard stone model.
AB  - Despite the real effectiveness and successful results of shock wave application,
      the effect of some varying parameters, namely number of shock wave (SW)
      electrical discharge value (kV), projection of the shock waves and electrode age
      are still to be evaluated. By using a standard stone model, we evaluated the real
      effect of the projection of shock waves and electrode age on the degree of stone
      disintegration. Our results indicated no significant relationship between the kV
      value and the degree of stone disintegration. However, as the number of SW
      increased, the rate of disintegration became evident. On the other hand,
      application of the same number of SW from two different angles revealed more
      effective disintegration rate on standard stone model. Thus SW number, age of the
      electrode and the projection of shock waves seemed to be important in the
      disintegration of the stones.

PMID- 9285299
TI  - Scrotal bruising as a sign of retroperitoneal haematoma following extracorporeal
      shock wave lithotripsy.

PMID- 9285300
TI  - Multivariate evaluation of prognostic determinants for renal cell carcinomas
      which are metastatic at initial diagnosis.
AB  - To clarify the relative importance of clinicopathological factors potentially
      affecting the survival of individuals initially diagnosed as having metastatic
      renal cell carcinoma (RCC), univariate and multivariate analyses using Cox's
      proportional hazards model were performed for 111 RCC patients who were admitted
      to four hospitals in Nagoya, Japan, between 1978 and 1993. Survival time was
      calculated from the date of diagnosis to the date of death or the end of May,
      1995. Nineteen factors (17 clinically applicable before treatment and 2
      histological in nature) were included for assessment. Univariate analysis
      revealed that 10 of the total 19 factors were significantly associated with
      patient survival. Multivariate analysis found 7 factors to be statistically
      significant determinants. Survival was further evaluated by categorizing the
      patients into three groups according to the number of the 7 factors. These groups
      showed clearly different survivals (log-rank test, p < 0.0001), confirming the
      importance of the 7 factors as definite determinants. They should therefore prove
      to be of advantage for classifying metastatic RCC patients when designing
      clinical prospective studies of immunotherapy and chemotherapy.

PMID- 9285301
TI  - Ureteroscopic management of lower ureteral stones: two years' experience.
AB  - A total of 140 ureteroscopies in 119 patients done between January 1992 and
      December 1994 at the Department of Urology, Hacettepe University Hospital, were
      reviewed. Factors such as previous ESWL therapy, previous surgery and use of in
      situ lithotripsy were noted. Success was defined as complete removal or
      disintegration and partial removal of the lower ureteral stones. All successes
      were confirmed by plain abdominal X-rays postoperatively. Of 140 stone
      manipulations attempted in 119 patients 106 (75.7%) were successful (in 80 by
      retrieval and in 26 by disintegration using electrohydraulic or laser).
      Perforation occurred in 4 of 13 cases where electrohydraulic lithotripsy was used
      for disintegration of stones. Extraction by ureteroscopic manipulation following
      extracorporeal shock wave lithotripsy (ESWL) was successful in all of the 12
      cases of lower ureteral calculi. The success rate was found to be low for lower
      ureteral stones in patients with previous open surgery (2/9). A total of 43.2% of
      the patients were medically indicated to be hospitalized following the procedure
      with a mean hospitalization time of 5 days (ranging in between 1 to 7 days).
      Ureteroscopy is an effective method for management of lower ureteral stones. Use
      of the electrohydraulic lithotriptor may be associated with a high percentage of
      complications. Previous ESWL may be associated with a high rate of success.
      Results in patients with previous open surgery are not encouraging. Although all
      patients can be subjected to the procedure on an outpatient basis, a significant
      percentage need a short hospitalization.

PMID- 9285302
TI  - Spontaneous fragmentation of a double J stent.
AB  - A variety of indications have made the use of double J stents routine in urology.
      Minimal and moderate side effects of ureteral stent are common, when the
      indwelling time exceeds 6 weeks the incidence of severe complications, like
      fragmentation increase. We report a case of stent fragmentation after an
      indwelling period of 12 months. Despite the variety of complications the severity
      requires close monitoring of the patient.

PMID- 9285303
TI  - Benign polyps with prostatic-type epithelium of the urethra and the urinary
      bladder.
AB  - The clinico-pathological features of nine urethral and urinary bladder polyps
      with prostate-type epithelium are described. The average age of the patients was
      46 years. Three patients previously had cystoscopy and the lesion was not noticed
      on the initial examination. The commonest presentation in this series was
      haematuria, dysuria and frequency of micturition. One patient presented with
      postmicturition dribble and another with haemospermia. The polyps contained acini
      and papillae lined by prostate-type epithelium which was confirmed by
      immunohistochemical tests for prostate specific antigen and prostate acid
      phosphatase. In this series no age versus location relationship could be
      established. Symptoms resolved following resection or initial biopsy followed by
      fulguration. Recurrence is extremely rare.

PMID- 9285304
TI  - Primary malignant lymphoma of the bladder. A case report and review of the
      literature.
AB  - Primary malignant lymphoma of the bladder is unusual. We report a case of primary
      malignant lymphoma arising in the urinary bladder. A 54-year-old woman was
      admitted to our hospital with the chief complaint of dysuria, on May 26, 1995.
      Examination of IVP, ultrasonography, cystoscopy suggested a non-papillary bladder
      tumour. Diagnosis was established by histological examination.

PMID- 9285305
TI  - Pharmacotherapy of benign prostatic hyperplasia: inhibitor of 5 alpha-reductase.
AB  - We studied the effects of 5 alpha-reductase inhibitor (finasteride) in the
      treatment of benign prostatic hyperplasia (BPH). This study is a randomized
      controlled trial. Sixty-two patients were treated with 5 alpha-reductase
      (finasteride 5 mg/day) and 61 patients (control group) with placebo for one year.
      Prostatic volume, maximal urine flow rate, AUA symptom scoring, residual urine
      volume and prostate-specific antigen (PSA) levels were evaluated at 3, 6, 9 and
      12 months. In the first 6 months prostatic volume decreased rapidly (20.5%), in
      the second 6 months it decreased slowly and reached the maximal rate (23.3%).
      Maximal urine flow rate increased in the second 6 months. AUA symptom scores
      decreased first at 3 months and were 4.6 points lower at the end of the 12th
      month. There were no significant changes in residual volume. The 5 alpha
      reductase inhibitor caused a 50% decrease in PSA levels, like in other studies.
      Because of the prolonged use of the drug, treatment with 5 alpha-reductase
      inhibitor is not tolerated by many patients and being expensive its future in the
      pharmacotherapy of BPH is unclear.

PMID- 9285306
TI  - Use of the holmium:YAG laser for urethral stricture under topical anaesthesia.

PMID- 9285307
TI  - Surgical results of complete hypospadias repair in two stages.
AB  - Between 1980 and 1992, 403 patients with hypospadias and with no previous
      operations were treated in Hyogo College of Medicine. Surgery was not performed
      in children younger than 3 years. The major points in the surgical repair were
      complete resection of the chordee, normal location of the meatus and reducing
      complications such as fistula formation or stricture. In order to achieve these
      aims we performed a two-stage repair, with the second operation at leat 12 months
      after the first one. In 57 of 245 patients with "chordee without hypospadias" and
      slight to moderate degree of hypospadias we performed surgery by the Crawford
      Ikoma technique, which is characterized by 3 layers of watertight continuous
      sutures at the time of urethroplasty. The incidence of postoperative fistulae was
      1.8%, the rate of strictures was 3.5%. After the Mays-Ikoma technique, where we
      perform a glandular urethroplasty in addition to chordectomy in the first stage,
      we diagnosed an urethral fistula in 7.9% and a stricture in 2.3%. A severe degree
      of hypospadias was seen in 158 patients. After performing the Crawford-Ikoma
      technique we acknowledged a rate of postoperative fistulae in 3.6% and strictures
      in 10.7%. The incidence of fistulae after the Mays-Ikoma technique was 8.9% and
      of strictures 1.1%. Altogether we found persistent chordee in 2 cases.

PMID- 9285308
TI  - Urethral caruncle with coexistence of intestinal heterotopia. A case report.
AB  - Urethral caruncle is one of the benign disorders which occurs frequently after
      the menopause. We describe a case of urethral caruncle with intestinal
      heterotopia, in which infiltration by lymphocytes, invagination of the urethral
      transitional epithelium causing nest formation, lumen formation, hypervascularity
      as well as teleangiectasia were observed, suggesting the occurrence of metaplasia
      in the transitional epithelium preceding the intestinal heterotopia. The
      aetiology and clinical significance of urethral caruncle exhibiting intestinal
      heterotopia are discussed.

PMID- 9285310
TI  - Testicular torsion: evaluation of contralateral testicular histology.
AB  - Infertility may occur in patients with unilateral testicular torsion whose
      contralateral testis is intact. Depending on this observation, the physicians
      have begun to examine the contralateral testis. In the present prospective study
      we aimed to examine the histopathologic alterations occurring in the
      contralateral testicle with time. Sixty adult male albino rats were included in
      the programme, and following experimental torsion the histopathologic findings,
      especially those in the contralateral testis, were evaluated after 4-12 weeks.
      Long-term and high degree torsion of the testicle led to varying degrees of
      deterioration in the germinal epithelium and interstitial cells of the
      contralateral testicle. Histopathologic alterations were reversed in 12 weeks.
      Tubular diameter and testicular volume also decreased in accordance with the
      histopathologic alteration. In our opinion, orchiectomy following torsion of one
      testicle will limit potential histopathologic alterations in the contralateral
      testicle.

PMID- 9285309
TI  - Relationship between semen quality improvement after varicocelectomy and
      preoperative levels of hypophyseal and gonadal hormones.
AB  - Evaluation of serum levels of FSH, LH, prolactin, testosterone and oestradiol is
      not predictive of the increases of sperm count after varicocelectomy. Increased
      level of oestradiol reflects the lack of possibility of sperm motility increase
      after varicocelectomy.

PMID- 9285311
TI  - The effect of alternate-day low dose prednisolone on bone age in children with
      steroid dependent nephrotic syndrome.
AB  - Radius, ulna, short bones (RUS), carpal (CARP) bone age (BA), tibial cortico
      diaphyseal (C/D) ratio and trabecular aspect were assessed in 19 children with
      steroid dependent nephrotic syndrome and 15 age matched healthy children. Both
      RUS and CARP BA were significantly lower than in the controls. Trabecular aspect
      and tibial C/D ratio did not show any statistical significance. There was a
      positive correlation between HSDS and RUS BA delay (r = -0.476, p < 0.05); CARP
      BA delay and RUS BA delay (r = 0.563, p < 0.01) and RUS BA and CARP BA (r =
      0.891, p < 0.001). In conclusion, RUS and CARP BA are both retarded and
      positively correlated in steroid dependent nephrotic children.

PMID- 9285312
TI  - Efficacy of enalapril after ineffective theophylline treatment on erythrocytosis
      after renal transplantation.
AB  - Erythrocytosis represents a common complication in renal allograft recipients.
      Traditional therapies including phlebotomy and bilateral native nephrectomies are
      cumbersome for both the clinical personnel and the patient. Recently,
      pharmacological agents such as angiotensin converting enzyme inhibitor and
      theophylline have been proposed as effective therapies for post-transplant
      erythrocytosis (PTE). We have treated a PTE patient successfully with enalapril
      without any side effects and renal dysfunction after theophylline treatment
      showed no improvement in PTE. A decline in Ht levels was independent of the
      changes in Epo levels during enalapril treatment. Although the mechanism
      underlying the beneficial effect of enalapril remains undetermined, enalapril is
      recommended for the initial treatment of PTE.

PMID- 9285313
TI  - Influence of some immune factors on the IL-6 and soluble IL-2 receptors in
      haemodialysed patients.
AB  - In respect to the immune deficiency state of long-term haemodialysed patients,
      both cytokines and their receptor disturbances have been taken into
      consideration. The purpose of our study was to evaluate the effect of uraemic and
      haemodialysis factors on the interleukin-6 and interleukin-2 soluble receptor
      levels and the reactivity after influenza vaccination. We have found that IL-6
      and IL-2 receptor levels were statistically significantly elevated (98.8 +/- 39
      pg/ml and 1557 +/- 544 U/ml, respectively) in serum of haemodialysed patients.
      The fact that increased immune complexes statistically correlated with soluble IL
      2 receptor levels (p < 0.01) was very interesting for us. In order to study the
      immunological response after vaccination, 10 patients have been investigated
      after influenza vaccination. Plasma samples were collected before, as well as 1
      and 4 weeks after vaccine administration. Antibody titres measured by
      haemagglutinin inhibition showed decreased antibody levels in haemodialysed
      patients. We conclude that the interleukin disturbance and the elevated
      interleukin-2 receptor levels together with the presence of circulating immune
      complexes can influence in some way the immune response of haemodialysed
      patients.

PMID- 9285314
TI  - Pharmacokinetics of recombinant human erythropoietin in children with chronic
      renal failure.
AB  - Basal erythropoietin (Epo) levels and single dose-pharmacokinetics of recombinant
      human erythropoietin (rhuEpo) were investigated in 8 predialysis (PD) patients
      (mean age 11.6 +/- 1.4 years) and in 8 patients on continuous ambulatory
      peritoneal dialysis (CAPD) (mean age 12.7 +/- 0.6 years). Basal Epo levels were
      found to be 1.0 +/- 0.0 mu/ml in PD group, 1.6 +/- 0.7 mu/ml in CAPD group and
      8.5 +/- 1.8 mu/ml in control group. Following administration of 50 mu/kg rhuEpo
      (s.c.) serum Epo concentration (Cmax) was 23.2 +/- 2.5 mu/ml in 18.5 +/- 2.6
      hours (tmax) in PD patients and 9.9 +/- 0.8 mu/ml in 26.8 +/- 7.7 hours in CAPD
      patients. Mean elimination half-lives (t1/2) were 13.3 +/- 1.9 hours and 13.5 +/-
      3.0 hours in PD patients and CAPD patients, respectively. The volume of
      distribution (Vd) was 840.0 +/- 100.0 ml/kg; the clearance (Epo Cl) was 37.0 +/-
      5.5 ml/kg/hour in PD patients. These values were significantly lower in PD
      patients than in CAPD patients (p < 0.05) (Vd; 1500 +/- 240.0 ml/kg; Epo Cl 110
      +/- 30.0 ml/kg/hour). During the course of CAPD, more efficient clearance of
      uraemic toxins that inhibit erythropoiesis and more rapid extraction of
      erythropoietin by erythroid precursors may cause higher Vd in CAPD patients than
      in PD patients.

PMID- 9285315
TI  - Influence of intraperitoneal vancomycin on peritoneal dialysis efficiency. A
      clinical study.
AB  - Peritonitis is a major complication of intermittent peritoneal dialysis (IPD);
      over 70% of the infections are caused by Gram-positive bacteria. Vancomycin (V)
      is the antibiotic of choice in the treatment of peritonitis caused by G(+). The
      influence of vancomycin on peritoneal transport in IPD patients has not been
      described before. We have investigated the effect of intraperitoneal vancomycin
      on dialysis efficiency in 8 IPD patients using dialysis solutions containing
      either lactate or acetate. The following parameters were measured: net
      ultrafiltration (UF), concentration ratios (D/P) of urea, creatinine, potassium,
      peritoneal clearances (ml/min) of urea, creatinine, potassium, mass transfer of
      sodium (MTNa), sodium sieving index (SCNa). It has been found that vancomycin
      significantly decreases D/P urea (p < 0.05) and creatinine (p < 0.05). We found
      also a significant decrease of mean clearance of urea (p < 0.05) and creatinine
      (p < 0.05). The mean clearance of potassium did not change significantly. There
      was no significant change in UF, MTNa, and SCNa. Our preliminary data suggest
      that vancomycin decreases the permeability of peritoneum for certain low
      molecules in IPD patients which may have a negative impact on dialysis
      efficiency.

PMID- 9285316
TI  - Privacy and disclosure: the psychological impact on gamete donors and recipients
      in assisted reproduction.

PMID- 9285317
TI  - Privacy versus disclosure in gamete donation: a clash of interest, of duties, or
      an exercise in responsibility?

PMID- 9285318
TI  - The controversy regarding privacy versus disclosure among patients using donor
      gametes in assisted reproductive technology.

PMID- 9285320
TI  - The controversy surrounding privacy or disclosure among donor gamete recipients.

PMID- 9285319
TI  - Parenting and secrecy issues related to children of assisted reproduction.

PMID- 9285321
TI  - Factors influencing patients' decision not to repeat IVF.
AB  - Women who did not pursue a second in vitro fertilization cycle after a failed
      cycle were surveyed. The major reason for not pursuing a second cycle was
      financial.

PMID- 9285322
TI  - Iodixanol as a density gradient medium for the isolation of motile spermatozoa.
AB  - PURPOSE: The purpose of this study was to establish concentrations of Iodixanol
      which could be used in a similar manner to the widely used Mini-Percoll technique
      for the separation of motile spermatozoa. METHODS: Various density gradient
      combinations of Iodixanol were compared for the isolation of motile spermatozoa
      from cryopreserved donor semen. The toxicity of Iodixanol was tested by its
      effect on the growth of two-cell mouse embryos and fresh sperm survival. RESULTS:
      The best sperm recovery (32%) came from the pellet of sperm passing through a
      discontinuous gradient of 25% over 40% OptiPrep after 20 min of centrifugation at
      400 g. There was no evidence of toxicity to mouse embryo growth or sperm
      survival. CONCLUSIONS: Iodixanol (OptiPrep; Nycomed) provides a satisfactory
      alternative for the efficient separation of motile spermatozoa for ART
      procedures.

PMID- 9285323
TI  - Silane-coated silica particle colloid processing of human sperm.
AB  - PURPOSE: The purpose of this study was to determine differences in the quality of
      human sperm processed through different lots of silane-coated silica particle
      colloid solutions. The objectives were to compare (a) sperm kinematic parameters,
      (b) the sperm acrosome status, (c) the membrane integrity of the head and tail
      regions, (d) the DNA normality, and (e) the heat-inducible hyperactivation
      motility after processing sperm through either a Silane-coated silica particle
      colloid solution, a Percoll solution, or a simple centrifuge sperm wash
      (control). METHODS: Sperm cells were derived from pooled cryopreserved-thawed
      specimens of several donors (n = 10). The pooled sperm were divided and processed
      through either the centrifuge wash, the 90:47% two-layer Percoll, or one of three
      lots of silane-coated silica particle colloidal solutions from three vendors.
      Aliquots of sperm cells were analyzed using the Hamilton-Thorn HTM-C motility
      analyzer for differences in kinematics and hyperactivation. Sperm were also
      analyzed for membrane integrity at both head and tail regions, normal morphology,
      acrosome status, and viability. Sperm undergoing apoptosis were determined using
      the acridine orange stain. Processed sperm were also incubated at 40 degrees C
      for 4 hr and the quality of the sperm was assessed using the heat-induced
      hyperactivation and motility parameter. RESULTS: The data showed that after sperm
      processing, the number of sperm recovered was higher for the three lots of
      colloids (silane-coated silica particle colloid solutions) compared with Percoll
      processing. Total sperm motility was higher in the colloidal washes compared with
      the control. There were no differences in motility between Percoll- and colloid
      processed sperm. In contrast, the percentages of sperm exhibiting progressive
      motility or hyperactivation varied among the different lots of colloid solutions.
      The Percoll wash solution yielded the highest percentage of sperm with intact
      tail membranes, whereas some lots of colloid solutions disrupted sperm head
      membranes. The percentages of sperm undergoing apoptosis varied for the different
      lots of colloid solutions. There was a marked increase in hyperactivation
      associated with one colloid solution after heat induction. CONCLUSIONS: The
      results demonstrated variability in the different lots of silane-coated silica
      particle colloid solutions for processing sperm. Each lot of colloid solution
      excelled at improving different sperm parameters. The silane-coated silica
      particle colloid solutions were shown to be effective in recovering motile sperm
      compared with Percoll but the types of motility and sperm quality varied for the
      different lots of colloid solutions. Due to the variability in lots of silane
      coated silica colloid solutions, reported studies based on only one lot or one
      source of colloid solution may be difficult to interpret. Furthermore, it may be
      advantageous to select the best lot of silane-coated silica particle colloid
      solution to produce the highest number of sperm exhibiting the ideal parameters
      for use in assisted reproduction technologies.

PMID- 9285324
TI  - Improved motile sperm recovery by a hyperosmotic Percoll gradient.
AB  - PURPOSE: Our purpose was to investigate whether a new, relatively hyperosmotic
      Percoll gradient, Enhance-S, can improve total motile sperm recovery rates
      compared with the commonly used Percoll gradient Perception. METHODS: Semen
      specimens from each of 17 donors were divided into two equal aliquots. One part
      was washed using Percoll Perception, while the other was prepared using Percoll
      Enhance-S. RESULTS: Compared to the unwashed specimen, sperm motion
      characteristics (motility and velocity) improved significantly after Percoll
      separation using either the Perception or the Enhance-S gradient. There was no
      difference in motility or velocity in spermatozoa recovered after wash with
      either of the two preparations. However, the total motile sperm recovery was
      significantly higher using the Percoll Enhance-S gradient than with the Percoll
      Perception gradient (P < 0.0024). CONCLUSION: The new Percoll Enhance-S gradient
      provides significantly more total motile sperm than the Percoll Perception
      gradient.

PMID- 9285325
TI  - Nonessential amino acids and glutamine decrease the time of the first three
      cleavage divisions and increase compaction of mouse zygotes in vitro.
AB  - PURPOSE: The objective of this study was to determine the effect of supplementing
      embryo culture media with amino acids on the duration of the first three cell
      cycles of mouse zygotes in vitro. METHODS: Zygotes were cultured in the presence
      of different groups of amino acids and cleavage assessed every 30 min. RESULTS:
      Culture of zygotes with Eagle's nonessential amino acids and glutamine
      significantly reduced the time of cleavage divisions to the eight-cell stage
      compared to culture without amino acids. Beneficial effects of amino acids were
      found to be cumulative over time. Nonessential amino acids and glutamine also
      increased the percentage of eight-cells that compacted after 57 hr of culture
      compared to embryos in medium devoid of amino acids. CONCLUSIONS: The present
      data suggest that media for the development of cleavage-stage embryos, such as in
      clinical IVF, should be supplemented with Eagle's nonessential amino acids and
      glutamine.

PMID- 9285327
TI  - Successful triplet pregnancy in a 51-year-old woman after oocyte donation.

PMID- 9285326
TI  - Effects of epidermal growth factor on preimplantation mouse embryos.
AB  - PURPOSE: Our purpose was to clarify the effects of epidermal growth factor (EGF)
      on mouse preimplantation embryos. METHODS: We examined the effect of EGF on two
      cell and four-cell stage mouse embryos cultured in vitro. In preimplantation
      embryos, we analyzed the binding of 125I-EGF by autoradiography and EGF receptor
      mRNA by the reverse transcription-polymerase chain reaction. RESULTS: At more
      than 0.005 ng/ml, EGF relieved the two-cell block and regulated the
      differentiation of morula-stage embryos. These effects were negated by antiserum.
      EGF did not exhibit any marked effect on embryos between the four-cell and the
      morula stages. Specific binding for EGF and EGF receptor mRNA was detected during
      and after the morula stage. CONCLUSIONS: The effects of EGF on preimplantation
      mouse embryos differed according to the stage of development, promoting cleavage
      before the four-cell stage and regulating differentiation after the morula stage.
      This regulatory action is thought to be transmitted to the cells via EGF
      receptors.

PMID- 9285328
TI  - In vitro response of Escherichia coli to antibiotics and ultrasound at various
      insonation intensities.
AB  - Microbial infections on implanted medical devices are difficult to treat.
      Application of 70 kHz ultrasonic irradiation to gentamicin treatment greatly
      enhanced the action of the antibiotic in terms of reduced viable bacterial
      concentrations. Ultrasonic irradiation was carried out at various insonation
      intensities that were noninhibitory in the absence of antibiotic. Synergistic
      killing was observed to be a function of ultrasonic intensity. Greatest killing
      (approximately 5 log reduction in viable population) was realized at full
      intensity (4.5 W/cm2), and decreased with reductions in power density. At lowest
      intensity (10 mW/cm2), no significant acoustic enhanced killing was noted.

PMID- 9285330
TI  - Hematological aspects of biocompatibility--review article.
AB  - The development and improvement of medical devices and artificial organs is
      critically dependent on the realisation of the importance of the interactions
      between materials and body tissues. In this regard, the evaluation of
      biocompatibility assumes paramount importance. This paper reviews the
      hematological aspects of biocompatibility--the responses evoked by the material
      as well as the methods for their detection. The paper also mentions a few methods
      of improvement of material compatibility.

PMID- 9285331
TI  - Proliposome-based transdermal delivery of levonorgestrel.
AB  - Mesophasic proliposomal system for levonorgestrel was developed and evaluated
      both in vitro and in vivo. The vesicles were mostly unilamellar, however, few
      vesicles were multilamellar which budded off spontaneously upon hydration. The
      release of drug from this system adhered to zero order kinetics. The effect of
      alcohols and volatile oils on transdermal flux was investigated. The flux was
      found to be the highest for alcohol, and followed by that for lemon oil. The in
      vivo studies indicate the requirement for a loading dose, since, a significant
      lag phase was observed before the therapeutic levels were reached. This system
      was, however, superior to the PEG-based ointment system which was employed as the
      control formulation. The results demonstrate the potential of proliposomal system
      for efficacious transdermal delivery of hydrophobic drugs.

PMID- 9285329
TI  - In vitro assessment of the biological activity of basic fibroblast growth factor
      released from various polymers and biomatrices.
AB  - The kinetics of controlled release of basic fibroblast growth factor (bFGF) from
      polymers (sutures, polycarbonate, Hydron, and Elvax), biopolymers (alginate), and
      biomatrices (lens capsules), and conditions for storage of bFGF (temperature,
      plastic type, heparin) were evaluated in vitro. Tissue culture proliferation
      bioassays with 3T3 fibroblasts, showed that only lens capsules with bFGF had a
      sustained release of bFGF for up to three weeks. The other materials released all
      of the 'bound' bFGF with two hours or produced an inflammatory response in vivo.
      Therefore, the lens tissue had the most potential for controlled long-term
      delivery of bFGF in vivo. These studies emphasise the importance of in vitro
      analysis of release kinetics of growth factors from a range of materials as a
      basis for potential in vivo applications.

PMID- 9285332
TI  - Predicting the impact response of a nonlinear single-degree-of-freedom shock
      absorbing system from the measured step response.
AB  - We measured the step response of a surrogate human pelvis/impact pendulum system
      at force levels between 50 and 350 N. We then fit measured response curves with
      four different single-degree-of-freedom models, each possessing a single mass,
      and supports of the following types: standard linear solid, Voigt, Maxwell, and
      spring. We then compared model predictions of impact force during high-energy
      collisions (pendulum impact velocity ranging from 1.16 to 2.58 m/s) to force
      traces from actual impacts to the surrogate pelvis. We found that measured peak
      impact forces, which ranged from 1700 to 5600 N, were best predicted by the mass
      spring, Maxwell, and standard linear solid models, each of which had average
      errors less than 3 percent. Reduced accuracy was observed for the commonly used
      Voigt model, which exhibited an average error of 10 percent. Considering that the
      surrogate pelvis system used in this study exhibited nonlinear stiffness and
      damping similar to that observed in simulated fall impact experiments with human
      volunteers, our results suggest that these simple models allow-impact forces in
      potentially traumatic falls to be predicted to within reasonable accuracy from
      the measured response of the body in safe, simulated collisions.

PMID- 9285333
TI  - The predictive value of stress shielding for quantification of adaptive bone
      resorption around hip replacements.
AB  - The presence of a femoral hip stem changes local mechanical signals inside the
      surrounding bone. In this study we examined the hypothesis that the eventual loss
      of bone can be estimated from the initial patterns of elastic energy deviation,
      as determined in FE models of the intact bone and the operated femur. For that
      purpose two hypothetical relations between elastic energy reduction and
      resorption were investigated. Their estimates of bone loss were compared to the
      results of iterative computer simulations. Two kinds of FE model were used, and
      in each stem stiffness and remodeling threshold (a measure of "biological
      reactivity") were varied. Provided that reasonable values of the remodeling
      threshold are assumed and that the stem is firmly bonded to the bone, we found
      that the difference between direct estimates and simulation models was 4 percent
      of bone loss. It is therefore concluded that initial patterns of elastic energy
      deviation give a reasonable indication of expected bone loss.

PMID- 9285334
TI  - Ultrasonic wave velocity measurement in small polymeric and cortical bone
      specimens.
AB  - A system was refined for the determination of the bulk ultrasonic wave
      propagation velocity in small cortical bone specimens. Longitudinal and shear
      wave propagations were measured using ceramic, piezoelectric 20 and 5 MHz
      transducers, respectively. Results of the pulse transmission technique were
      refined via the measurement of the system delay time. The precision and accuracy
      of the system were quantified using small specimens of polyoxymethylene,
      polystyrene-butadiene, and high-density polyethylene. These polymeric materials
      had known acoustic properties, similarity of propagation velocities to cortical
      bone, and minimal sample inhomogeneity. Dependence of longitudinal and transverse
      specimen dimensions upon propagation times was quantified. To confirm the
      consistency of longitudinal wave propagation in small cortical bone specimens (<
      1.0 mm), cut-down specimens were prepared from a normal rat femur. Finally,
      cortical samples were prepared from each of ten normal rat femora, and Young's
      moduli (Eii), shear moduli (Gij), and Poisson ratios (Vij) were measured. For all
      specimens (bone, polyoxymethylene, polystyrene-butadiene, and high-density
      polyethylene), strong linear correlations (R2 > 0.997) were maintained between
      propagation time and distance throughout the size ranges down to less than 0.4
      mm. Results for polyoxymethylene, polystyrene-butadiene, and high-density
      polyethylene were accurate to within 5 percent of reported literature values.
      Measurement repeatability (precision) improved with an increase in the wave
      transmission distance (propagating dimension). No statistically significant
      effect due to the transverse dimension was detected.

PMID- 9285335
TI  - Inertial loading of the human cervical spine.
AB  - While the majority of experimental cervical spine biomechanics research has been
      conducted using slowly applied forces and/or moments, or dynamically applied
      forces with contact, little research has been performed to delineate the
      biomechanics of the human neck under inertial "noncontact" type forces. This
      study was designed to develop a comprehensive methodology to induce these loads.
      A minisled pendulum experimental setup was designed to test specimens (such as
      human cadaver neck) at subfailure or failure levels under different loading
      modalities including flexion, extension, and lateral bending. The system allows
      acceleration/deceleration input with varying wave form shapes. The test setup
      dynamically records the input and output strength information such as forces,
      accelerations, moments, and angular velocities; it also has the flexibility to
      obtain the temporal overall and local kinematic data of the cervical spine
      components at every vertebral level. These data will permit a complete
      biomechanical structural analysis. In this paper, the feasibility of the
      methodology is demonstrated by subjecting a human cadaver head-neck complex with
      intact musculature and skin under inertial flexion and extension whiplash loading
      at two velocities.

PMID- 9285337
TI  - A dynamic system model of an off-road cyclist.
AB  - To optimize the performance of off-road bicycle suspension systems, a dynamic
      model of the bicycle/rider system would be useful. This paper takes a major step
      toward this goal by developing a dynamic system model of the cyclist. To develop
      the cyclist model, a series of four vibrational tests utilizing random inputs was
      conducted on seven experienced off-road cyclists. This allowed the transfer
      functions for the arms and legs to be determined. To reproduce the essential
      features (i.e., resonance peaks) of the experimental transfer functions, the
      system model included elements representing the visceral mass along with the arms
      and legs. Through simulations, the frequency responses of the system model of the
      rider in each of the four tests were computed. Optimal stiffness and damping
      parameter values for each subject were determined by minimizing the difference
      between the experimental and simulation results. Good agreement between
      experimental and simulation results indicates that modeling the rider as a lumped
      parameter system with linear springs and dampers is possible.

PMID- 9285336
TI  - A numerical investigation of the mechanics of swelling-type intramedullary hip
      implants.
AB  - The novel concept of swelling-type intramedullary hip implants that attain self
      fixation by an expansion-fit mechanism resulting from controlled swelling of the
      implant (by absorption of body fluids) was examined in detail using a finite
      element model of the implant-femur system. Some of the potential advantages of
      this technique over traditional techniques include enhanced fixation, lower
      relative micromotions, improved bony ingrowth, and elimination of acrylic cement.
      The finite element model created in this study incorporated: (i) the major
      aspects of the three-dimensional geometry of the implant and femur, (ii) the
      anisotropic elastic properties of bone and implant materials and the changes in
      orientation of the principal axes of anisotropy along the length of the implant
      femur system, (iii) a layer of cancellous bone between the implant and cortical
      bone in the proximal femoral region, and (iv) frictional sliding between the bone
      and implant. The model was used to study quantitatively the parametric influence
      of various material design variables on the micromotions and stress fields in the
      bone-swelling-type implant system. The results of the finite element analyses
      were used to establish material behavior goals and provide targets for a material
      development study.

PMID- 9285338
TI  - Dynamic contact stress and rolling resistance model for total knee
      arthroplasties.
AB  - Problems associated with premature failure of total knee replacements (TKR's)
      include: wear, creep, and oxidation of ultrahigh-molecular-weight polyethylene
      (UHMWPe) as well as adverse tissue reactions to polyethylene wear debris. These
      problems are associated in part with the mechanical behavior of UHMWPe. In TKR's,
      contact stress analyses have been performed on the UHMWPe tibial component;
      however, most have employed simplified material properties and not accounted for
      joint kinematics. A nonlinear viscoelastic rolling model was developed for TKR's
      to predict the contact stress and rolling friction for varying rolling speed,
      conformity, applied load, and tibial plateau thickness. Results indicated that
      the contact stress increased and rolling friction decreased with increasing
      rolling speed. Effects of conformity, applied load, and tibial plateau thickness
      were consistent with previous models. At large rolling speeds, predicted peak
      contact stresses were almost twice their static value, resulting in a compound
      fatigue problem in UHMWPe components due to normal cyclic loading, moving point
      of contact, and velocity-dependent stresses.

PMID- 9285340
TI  - Measurement and simulation of water transport during freezing in mammalian liver
      tissue.
AB  - Optimization of cryosurgical procedures on deep tissues such as liver requires an
      increased understanding of the fundamental mechanisms of ice formation and water
      transport in tissues during freezing. In order to further investigate and
      quantify the amount of water transport that occurs during freezing in tissue,
      this study reports quantitative and dynamic experimental data and theoretical
      modeling of rat liver freezing under controlled conditions. The rat liver was
      frozen by one of four methods of cooling: Method 1-ultrarapid "slam cooling" (>
      or = 1000 degrees C/min) for control samples; Method 2-equilibrium freezing
      achieved by equilibrating tissue at different subzero temperatures (-4, -6, -8, 
      10 degrees C); Method 3-two-step freezing, which involves cooling at 5 degrees
      C/min. to -4, -6, -8, -10 or -20 degrees C followed immediately by slam cooling;
      or Method 4-constant and controlled freezing at rates from 5-400 degrees C/min.
      on a directional cooling stage. After freezing, the tissue was freeze
      substituted, embedded in resin, sectioned, stained, and imaged under a light
      microscope fitted with a digitizing system. Image analysis techniques were then
      used to determine the relative cellular to extracellular volumes of the tissue.
      The osmotically inactive cell volume was determined to be 0.35 by constructing a
      Boyle van't Hoff plot using cellular volumes from Method 2. The dynamic volume of
      the rat liver cells during cooling was obtained using cellular volumes from
      Method 3 (two-step freezing at 5 degrees C/min). A nonlinear regression fit of a
      Krogh cylinder model to the volumetric shrinkage data in Method 3 yielded the
      biophysical parameters of water transport in rat liver tissue of: Lpg = 3.1 x 10(
      13) m3/Ns (1.86 microns/min-atm) and ELp = 290 kJ/mole (69.3 kcal/mole), with chi
      squared variance of 0.00124. These parameters were then incorporated into the
      Krogh cylinder model and used to simulate water transport in rat liver tissue
      during constant cooling at rates between 5-100 degrees C/min. Reasonable
      agreement between these simulations and the constant cooling rate freezing
      experiments in Method 4 were obtained. The model predicts that the water
      transport ceases at a relatively high subzero temperature (-10 degrees C), such
      that the amount of intracellular ice forming in the tissue cells rises from
      almost none (= extensive dehydration and vascular expansion) at < or = 5 degrees
      C/min to over 88 percent of the original cellular water at > or = 50 degrees
      C/min. The theoretical simulations based on these experimental methods may be of
      use in visualizing and predicting freezing response, and thus can assist in the
      planning and implementing of cryosurgical protocols.

PMID- 9285339
TI  - A finite element solution for the anisotropic biphasic theory of tissue
      equivalent mechanics: the effect of contact guidance on isometric cell traction
      measurement.
AB  - We present a method for solving the governing equations from our anisotropic
      biphasic theory of tissue-equivalent mechanics (Barocas and Tranquillo, 1997) for
      axisymmetric problems. A mixed finite element method is used for discretization
      of the spatial derivatives, and the DASPK subroutine (Brown et al., 1994) is used
      to solve the resulting differential-algebraic equation system. The preconditioned
      GMRES algorithm, using a preconditioner based on an extension of Dembo's (1994)
      adaptation of the Uzawa algorithm for viscous flows, provides an efficient and
      scaleable solution method, with the finite element method discretization being
      first-order accurate in space. In the cylindrical isometric cell traction assay,
      the chosen test problem, a cylindrical tissue equivalent is adherent at either
      end to fixed circular platens. As the cells exert traction on the collagen
      fibrils, the force required to maintain constant sample length, or load, is
      measured. However, radial compaction occurs during the course of the assay, so
      that the cell and network concentrations increase and collagen fibrils become
      aligned along the axis of the cylinder, leading to cell alignment along the axis.
      Our simulations predict that cell contact guidance leads to an increase in the
      load measured in the assay, but this effect is diminished by the tendency of
      contact guidance to inhibit radial compaction of the sample, which in turn
      reduces concentrations and hence the measured load.

PMID- 9285342
TI  - Relationships between alveolar size and fibre distribution in a mammalian lung
      alveolar duct model.
AB  - A finite element model, comprising an assemblage of tetrakaidecahedra or
      truncated octahedra, is used to represent an alveolar duct unit. The dimensions
      of the elastin and collagen fibre bundles, and the surface tension properties of
      the air-liquid interfaces, are based on available published data. Changes to the
      computed static pressure-volume behavior with variation in alveolar dimensions
      and fibre volume densities are characterized using distensibility indices (K).
      The air-filled lung distensibility (Ka) decreased with a reduction in the
      alveolar airspace length dimensions and increased with a reduction of total fibre
      volume density. The saline-filled lung distensibility (Ks) remained constant with
      alveolar dimensions and increased with decreasing total fibre volume density. The
      degree of geometric anisotropy between the duct lumen and alveoli was computed
      over pressure-volume cycles. To preserve broadly isotropic behavior, parenchyma
      with smaller alveolar airspace length dimensions required higher concentrations
      of fibres located in the duct and less in the septa in comparison with parenchyma
      of larger airspace dimensions.

PMID- 9285341
TI  - A new fundamental bioheat equation for muscle tissue: Part I--Blood perfusion
      term.
AB  - A new model for muscle tissue heat transfer has been developed using Myrhage and
      Eriksson's [23] description of a muscle tissue cylinder surrounding secondary (s)
      vessels as the basic heat transfer unit. This model provides a rational theory
      for the venous return temperature for the perfusion source term in a modified
      Pennes bioheat equation, and greatly simplifies the anatomical description of the
      microvascular architecture required in the Weinbaum-Jiji bioheat equation. An
      easy-to-use closed-from analytic expression has been derived for the difference
      between the inlet artery and venous return temperatures using a model for the
      countercurrent heat exchange in the individual muscle tissue cylinders. The
      perfusion source term calculated from this model is found to be similar in form
      to the Pennes's source term except that there is a correction factor or
      efficiency coefficient multiplying the Pennes term, which rigorously accounts for
      the thermal equilibration of the returning vein. This coefficient is a function
      of the vascular cross-sectional geometry of the muscle tissue cylinder, but
      independent of the Peclet number in contrast to the recent results in Brinck and
      Werner [8]. The value of this coefficient varies between 0.6 and 0.7 for most
      muscle tissues. In part II of this study a theory will be presented for
      determining the local arterial supply temperature at the inlet to the muscle
      tissue cylinder.

PMID- 9285343
TI  - Pulmonary airway reopening: effects of non-Newtonian fluid viscosity.
AB  - This paper considers the effects of non-Newtonian lining-fluid viscosity,
      particularly shear thinning and yield stress, on the reopening of the airways.
      The airway was simulated by a very thin, circular polyethylene tube, which
      collapsed into a ribbon-like configuration. The non-Newtonian fluid viscosity was
      described by the power-law and Herschel-Buckley models. The speed of airway
      opening was determined under various opening pressures. These results were
      collapsed into dimensionless pressure-velocity relationships, based on an assumed
      shear rate gamma = U/(0.5 H), where U and H are the opening velocity and fluid
      film thickness, respectively. It was found that yield stress, like surface
      tension, increases the yield pressure and opening time. However, shear thinning
      reduces the opening time. An increased film thickness of the non-Newtonian lining
      fluid generally impedes airway reopening; a higher pressure is needed to initiate
      the airway reopening and a longer time is required to complete the opening
      process.

PMID- 9285344
TI  - Gas dispersion in a model pulmonary bifurcation during oscillatory flow.
AB  - In order to clarify the gas transport process in high-frequency oscillation, we
      measured the axial velocity profile and the axial effective diffusivity in a
      single asymmetric bifurcating tube, based on the Horsfield airway model, with
      sinusoidally oscillatory flow. The axial velocity profiles were measured using a
      laser-Doppler velocimeter, and the effective diffusivities were evaluated using a
      simple bolus injection method. The axial velocity profile was found to be
      nonuniform, promoting axial gas dispersion by the spread of the concentration
      profile and lateral mixing. The geometric asymmetry of the bifurcation was
      responsible for the difference in gas transport between the main bronchi. The
      axial gas transport in the left main bronchus was 2.3 times as large as that of
      the straight tube, whereas the gas transport in the right main bronchus was
      slightly larger than that of the straight tube. Thus localized variation in gas
      transport characterized the heterogeneous respiratory function of the lung.

PMID- 9285345
TI  - Effects of frictional losses and pulsatile flow on the collapse of stenotic
      arteries.
AB  - High-grade stenosis can produce conditions in which the artery may collapse. A
      one-dimensional numerical model of a compliant stenosis was developed from the
      collapsible tube theory of Shapiro. The model extends an earlier model by
      including the effects of frictional losses and unsteadiness. The model was used
      to investigate the relative importance of several physical parameters present in
      the in vivo environment. The results indicated that collapse can occur within the
      stenosis. Frictional loss was influential in reducing the magnitude of collapse.
      Large separation losses could prevent collapse outright even with low downstream
      resistances. However, the degree of stenosis was still the primary parameter
      governing the onset of collapse. Pulsatile solutions demonstrated conditions that
      produce cyclic collapse within the stenosis. This study predicts certain
      physiologic conditions in which collapse of arteries may occur for high-grade
      stenoses.

PMID- 9285346
TI  - Experimental study of steady and pulsatile flows in cerebral aneurysm model of
      various sizes at branching site.
AB  - Pulsatile and steady flow fields in cerebrovascular aneurysm models of various
      sizes are presented in terms of laser-Doppler velocimetry measurements and flow
      visualization. The bifurcation angle was 140 deg and volume flow rate ratio
      between the branches was 3:1. The mean, peak, and minimal Reynolds numbers based
      on the bulk average velocity and diameter of the parent vessel were 600, 800, and
      280, respectively. It is found that among the tested sizes there exists a middle
      range of aneurysm sizes, above and below which the forced-vortex inside the
      aneurysmal model is weaker and lacking, respectively, whereas in the middle range
      of the tested sizes the forced vortex is stronger and the fluctuation level is
      higher near the dome. The present results also identify the major fluid dynamic
      factors of the aneurysmal promotion or rupture for the medium and larger
      aneurysms, respectively. Furthermore, the maximum fluctuation intensity is found
      to increase with aneurysm size. The locations of the maximum fluctuation
      intensity are found to occur in the bifurcation area or at the neck instead of
      intra-aneurysm.

PMID- 9285347
TI  - Wall shear rate distribution in an abdominal aortic bifurcation model: effects of
      vessel compliance and phase angle between pressure and flow waveforms.
AB  - The goal of this study was to determine how vessel compliance (wall motion) and
      the phase angle between pressure and flow waves (impedance phase angle) affect
      the wall shear rate distribution in an atherogenic bifurcation geometry under
      sinusoidal flow conditions. Both rigid and elastic models replicating the human
      abdominal aortic bifurcation were fabricated and the wall shear rate distribution
      in the median plane of the bifurcation was determined using the photochronic flow
      visualization method. In the elastic model, three phase angle conditions were
      simulated (+12, -17, -61 deg), and the results compared with those obtained in a
      similar rigid model. The study indicates a very low (magnitude close to zero) and
      oscillatory wall shear rate zone within 1.5 cm distal to the curvature site on
      the outer (lateral) wall. In this low shear rate zone, unsteadiness (pulsatility)
      of the flow greatly reduces the mean (time-averaged) wall shear rate level.
      Vessel wall motion reduces the wall shear rate amplitude (time-varying component)
      up to 46 percent depending on the location and phase angle in the model. The mean
      wall shear rate is less influenced by the wall motion, but is reduced
      significantly in the low shear region (within 1.5 cm distal to the curvature site
      on the outer wall), thus rendering the wall shear rate waveform more oscillatory
      and making the site appear more atherogenic. The effect of the phase angle is
      most noteworthy on the inner wall close to the flow divider tip where the mean
      and amplitude of wall shear rate are 31 and 23 percent lower, respectively, at
      the phase angle of -17 deg than at -61 deg. However, the characteristics of the
      wall shear rate distribution in the low shear rate zone on the outer wall that
      are believed to influence localization of atherosclerotic disease, such as the
      mean wall shear rate level, oscillation in the wall shear rate waveform, and the
      length of the low and oscillatory wall shear rate zone, are similar for the three
      phase angles considered. The study also showed a large spatial variation of the
      phase angle between the wall shear stress waveform and the circumferential stress
      waveform (hoop stress due to radial artery expansion in response to pressure
      variations) near the bifurcation (up to 70 deg). The two stresses became more out
      of phase in the low mean shear rate zone on the outer wall (wall shear stress
      wave leading hoop stress wave as much as 125 deg at the pressure-flow phase angle
      of -61 deg) and were significantly influenced by the impedance phase angle.

PMID- 9285349
TI  - Evaluation of the proximal flow field to circular and noncircular orifices of
      different aspect ratios.
AB  - Investigations of valvular regurgitation attempt to specify flow field
      characteristics and apply them to the proximal isovelocity surface area (PISA)
      method for quantifying regurgitant flow. Most investigators assume a
      hemispherical shape to these equivelocity shells proximal to an axisymmetric
      (circular) orifice. However, in vivo flow fields are viscous and regurgitant
      openings vary in shape and size. By using centerline profiles and isovelocity
      surfaces, this investigation describes the flow field proximal to circular and
      elliptical orifices. Steady, proximal flow fields are obtained with two- and
      three-dimensional computational fluid dynamic (CFD) simulations. These
      simulations are verified by in vitro, laser-Doppler velocimetry (LDV)
      experiments. The data show that a unique, normalized proximal flow field results
      for each orifice shape independent of orifice flow or size. The distinct
      differences in flow field characteristics with orifice shape may provide a
      mechanism for evaluating orifice characteristics and regurgitant flows. Instead
      of the hemispherical approximation technique, this study attempts to show the
      potential to define a universal flow evaluation method based on the details of
      the flowfield according to orifice shape. Preliminary results indicate that
      Magnetic Resonance (MR) and Color Doppler (CD) may reproduce these flow details
      and allow such a procedure in vivo.

PMID- 9285348
TI  - Hemodynamic simulations and computer-aided designs of graft-artery junctions.
AB  - Severe occlusion of graft-artery junctions due to restenosis, e.g., excessive
      tissue overgrowth and renewed plaque formation, may occur within a few months or
      years after bypass surgery. Our hypothesis is that nonuniform hemodynamics,
      represented by large sustained wall shear stress gradients, trigger abnormal
      biological processes leading to rapid restenosis and hence early graft failure.
      In turn, this problem may be significantly mitigated by designing graft-artery
      bypass configurations for which the wall shear stress gradient (WSSG) is
      approximately zero and hence nearly uniform hemodynamics are achieved. Focusing
      on the distal end of several femoral artery bypass junctions, a validated finite
      volume code has been used to compute the transient three-dimensional velocity
      vector fields and its first and second surface derivatives in order to test the
      idea. Specifically, it is shown that the Taylor patch, which generates higher
      patency rates than standard end-to-side anastomoses, exhibits lower WSSG levels
      than standard configurations, and that further geometric design improvements
      reduce the WSSG in magnitude and local extent even more.

PMID- 9285350
TI  - LDA measurements of velocities in a simulated collapsed tube.
AB  - A perspex (plexiglas) tube was locally deformed into an almost bi-lobar interior
      cross section, representative of the localized throat at the downstream end of a
      collapsed tube conveying a flow. The axial and transverse (parallel to the long
      axis of the deformed cross section) components of fluid velocity were measured in
      a dense rectangular grid of points covering the whole cross section, at 15 axial
      sites between one diameter upstream of and three diameters downstream of the
      center of the constriction. The Reynolds number based on undeformed tube diameter
      and mean velocity was 705. Results are presented both as surfaces showing the
      variation of each component over the cross section and as velocity vector
      profiles. The overall changes in velocity in the streamwise direction are
      presented in terms of the variation of the maximum and minimum of each component
      with axial position. Flow downstream of the throat consisted of two parallel side
      jets with a broad region of reverse flow in between. This pattern persisted until
      beyond 2.5 diameters downstream, by which point transverse inflow at the top and
      bottom of the cross section had converted the side jets into a complete annulus
      of axial velocity surrounding a central deficit. Jet velocities and reverse flow
      disappeared relatively abruptly before three diameters downstream.

PMID- 9285351
TI  - A protocol to evaluate semi-rigid pedicle screw systems.
AB  - The objective of the current study was to develop an in vitro testing protocol to
      evaluate semi-rigid pedicle screw devices. A corpectomy model protocol exists to
      evaluate rigid spinal implants; however, semi-rigid devices are contraindicated
      for this condition. This paper describes a technique that simulates more closely
      the conditions a semi-rigid device would see in vivo. Finally, the new testing
      protocol is used to evaluate the DDS pedicle screw-cable system. Benefits and
      shortcomings of the new protocol are discussed.

PMID- 9285352
TI  - Expression of serotonin transporter mRNA in rat brain: presence in neuronal and
      non-neuronal cells and effect of paroxetine.
AB  - The expression of serotonin transporter mRNA in rat brain was-examined by in situ
      hybridisation. Hybridisation was observed in cells of the known serotonergic
      nuclei and no other neuronal populations. It was also associated with ependymal
      cells of the aqueduct which may indicate a specialisation of this part of the
      ventricular system in anatomical and neurophysiological terms. The effect of the
      selective serotonin reuptake inhibitor paroxetine on neuronal expression of the
      serotonin transporter mRNA was examined. Quantitation at the cellular level in
      the dorsal and median raphe nuclei was carried out by analysis of the mean number
      of silver grains per cell in autoradiographed sections. No significant change (P
      > 0.1) in serotonin transporter mRNA expression was observed following 21 day
      administration of paroxetine (5 mg/kg per day).

PMID- 9285353
TI  - A monoclonal antibody shows discrete cellular and subcellular localizations of
      mGluR1 alpha metabotropic glutamate receptors.
AB  - The metabotropic glutamate receptor, mGluR1 alpha, is postsynaptic in excitatory
      synapses in many populations of neurons and mediates long-term responses. The
      present study defines the distribution of this receptor using a new, highly
      specific monoclonal antibody to mGluR1 alpha. Overall distribution of
      immunostaining was similar to that described previously with polyclonal
      antibodies, including prominent staining in the olfactory bulb, interneurons of
      the CA1 hippocampus stratum oriens/alveus, globus pallidus, thalamus, Purkinje
      cells and in cells of the outer dorsal cochlear nucleus and with little or low
      staining in principal cells of the cerebral cortex and hippocampus.
      Interestingly, the well-known association of mGluR1 alpha receptors with
      neocortical interneurons was even more prevalent than previously noted with
      polyclonal antibodies. Ultrastructural studies in the hippocampus and cerebellum
      showed dense immunoperoxidase staining in postsynaptic membranes and densities
      and in perisynaptic and extrasynaptic membranes, as well as substantial
      cytoplasmic staining associated with organelles, especially the endoplasmic
      reticulum.

PMID- 9285354
TI  - Evidence for the existence of galanin receptors on cultured astrocytes of rat
      CNS: colocalization with cholinergic receptors.
AB  - The cellular localization of binding sites for [125I]galanin was studied in
      explant cultures of rat neocortex, cerebellum, locus coeruleus and spinal cord by
      means by of autoradiography. Binding sites for the peptide were observed on a
      great number of astrocytes in all CNS regions studied. In addition to astrocytes,
      many neurones were intensely labelled by [125I]galanin. Binding of [125I]galanin
      (10(-8) M) to both astrocytes and neurones was markedly reduced or inhibited by
      the unlabelled peptide at high concentration (10(-6) M), suggesting 'specific'
      binding of the radioligand. Evidence for the colocalization of galanin and
      cholinergic receptors on astrocytes was provided by combined autoradiographic and
      immunohistochemical studies. Many astrocytes were labelled by [125I]galanin and
      immunostained with antibodies to either muscarinic or nicotinic receptors.
      Electrophysiological studies revealed that addition of galanin (10(-9) to 10(-7)
      M) to the bathing fluid caused a dose-dependent hyperpolarization of the majority
      of astrocytes studied. When galanin (10(-8) M) and the cholinergic agonists
      muscarine and nicotine (10(-6) M) were tested on the same astrocyte, all three
      compounds induced a hyperpolarization, suggesting a colocalization of functional
      galanin and cholinergic receptors on the glial membrane.

PMID- 9285355
TI  - Nicotinic receptor distribution in the human thalamus: autoradiographical
      localization of [3H]nicotine and [125I] alpha-bungarotoxin binding.
AB  - The thalamus plays a major role in relaying and transforming information that is
      relayed to the cortex and in turn modulates cortical outputs. The reticular
      nucleus projects to the other thalamic nuclei, modulating and integrating their
      activity. The distribution of high affinity nicotine and alpha-bungarotoxin
      (alpha BTX) receptors in the human thalamus has been investigated by radioligand
      autoradiography in post mortem human tissue. [3H]nicotine binding in the human
      thalamus was high in most thalamic nuclei, especially in the lateral dorsal, the
      medial geniculate, lateral geniculate and anterior nuclei. The distribution of
      [125I] alpha BTX binding was quite distinct from [3H]nicotine binding. [125I]
      alpha BTX binding was generally lower (< 0.26-11.62 fmol/mg protein compared with
      6.68-36.17 fmol/mg protein for nicotine binding) and concentrated in the
      reticular nucleus, with discrete groups of cells displaying higher binding in the
      latter. These results indicate differences between the distribution of nicotinic
      receptors in humans and those previously reported in mice and monkeys. Changes in
      high affinity nicotine and alpha BTX receptors in the thalamus may contribute to
      symptoms observed in neuropathological conditions associated with disorders of
      perception and movement such as Dementia with Lewy Bodies, Alzheimer's Disease
      and Schizophrenia.

PMID- 9285356
TI  - Distribution of alpha 1a-, alpha 1b- and alpha 1d-adrenergic receptor mRNA in the
      rat brain and spinal cord.
AB  - The technique of in situ hybridization with specific ribonucleotide probes was
      used to determine the distribution patterns of mRNA encoding the alpha 1a-, alpha
      1b- and alpha 1d-adrenoceptor (AR) subtypes in rat brain and spinal cord. The
      expression pattern of alpha 1a-AR mRNA has not been reported previously, and was
      found to be widespread throughout the rat central nervous system. High levels
      were found in regions of the olfactory system, several hypothalamic nuclei, and
      regions of the brainstem and spinal cord, particularly in areas related to motor
      function. Regions expressing moderate levels of mRNA for this receptor were the
      septum, bed nucleus of the stria terminalis, cerebral cortex, amygdala,
      cerebellum and pineal gland. Low expression levels were detected in the
      hippocampal formation. Most nuclei in the basal ganglia and thalamus expressed
      extremely low or undetectable levels of alpha 1a-AR mRNA. The expression patterns
      of the alpha 1b- and alpha 1d-AR mRNAs were similar to those described using
      oligonucleotide probes in earlier studies. High expression of alpha 1b-AR mRNA
      was noted in the pineal gland, most thalamic nuclei, lateral nucleus of the
      amygdala and dorsal and median raphe nuclei. Moderate expression levels were
      noted throughout the cerebral cortex, and in some olfactory, septal, and
      brainstem regions. The distribution of alpha 1d-AR mRNA was the most discrete of
      the three receptors examined. Expression was strong in the olfactory bulb,
      cerebral cortex, hippocampus, reticular thalamic nucleus, regions of the
      amygdala, motor nuclei of the brainstem, inferior olivary complex and spinal
      cord. Comparison of the distributions of the alpha 1a-, alpha 1b- and alpha 1d-AR
      mRNA suggests unique functional roles for each of these receptors.

PMID- 9285373
TI  - Role of phospholipase A2 in mammalian sperm-egg fusion: development of hamster
      oolemma fusibility by lysophosphatidylcholine.
AB  - Phospholipase A2 (PLA2), its localization on human sperm and its involvement in
      sperm-egg interaction, was investigated. Sperm-egg interaction was examined using
      an in vitro assay of the interaction between human sperm and zona-free or zona
      intact hamster egg. PLA2- specific antibodies and/or lysophosphatidylcholine
      (LPC) were added to the coincubation medium. PLA2 was localized on the anterior
      tip of the human sperm head by an immunogold silver staining method in light
      microscopy (IGSS) and TEM. PLA2-specific antibodies inhibited human sperm-zona
      free oocyte fusion significantly. LPC treatment allows interspecies fertilization
      of zona-intact hamster oocytes. PLA2 plays an important role in membrane-fusion
      events. This statement is supported by the fact that PLA2 is localized in the
      region where an exocytotic event, such as the acrosome reaction, occurs in the
      spermatozoon. PLA2-specific antibodies inhibited sperm-egg fusion, but not sperm
      oolemma adhesion. LPC may stimulate the fertilizing ability of spermatozoa and
      induce changes on the zona pellucida and on the oolemma promoting in sperm-egg
      fusion. Based on these findings, it is suggested that sperm PLA2 and one of its
      modulators, the LPC, may contribute to membrane-fusion events in mammalian
      fertilization.

PMID- 9285372
TI  - The influence of prolonged dexamethasone treatment of pregnant rats on the
      perinatal development of the adrenal gland of their offspring.
AB  - The effects of prolonged dexamethasone (Dx) administration to pregnant rats on
      the structure and function of the adrenal glands of fetal and neonatal offspring
      have been investigated by combined stereological and ultrastructural methods, as
      well as by metaphase index determination. Pregnant rats were injected
      subcutaneously with Dx (0.3 mg/kg body weight/day) during 5 days, starting from
      day 16 of gestation. The dams and their fetuses were killed 24 hr after the last
      injection. The neonatal offspring were killed in the same way on the 3rd and 14th
      day of life. Because in fetal and 3-day-old neonatal rats zona reticularis (ZR)
      was poorly defined and could not be clearly seen as a separate zone, zona
      fasciculata (ZF) and ZR were analyzed as one, inner zone (IZ). In 14-day-old rats
      ZF and ZR were analyzed separately. Proliferative activity of adrenocortical
      cells was estimated following the application of Vincristine sulphate. Dx
      treatment of pregnant rats induced a marked decrease of fetal adrenal gland
      volume and the volumes of zona glomerulosa + capsula (ZG + C) and IZ as the
      consequence of atrophic changes in the gland and reduction of the average volume
      and total number of adrenocortical cells. Similar morphometric changes were found
      in 3- and 14-day-old pups. However, in 3-day-old animals the number of cortical
      cells in the ZG was increased, whereas on the 14th postnatal day cortical cell
      number remained decreased only in the ZF. The multinuclear giant cells, numerous
      lymphocytes, and the resorption zones, present in the adrenal cortex of fetuses
      and 3-day-old pups of both experimental and control dams, were not seen in 14-day
      old offspring. These results demonstrate that prolonged treatment of pregnant
      rats with Dx in the period when intensive differentiation of the fetal
      hypothalamo-hypophyseal system takes place inhibits proliferative activity of
      adrenocortical cells and evokes considerable atrophic changes in the adrenal
      glands of offspring from 20 days gestation to 14 days after birth. The
      histological appearance of the adrenal cortex and the ultrastructure of
      adrenocortical cells suggest that cortical cell function was inhibited.

PMID- 9285374
TI  - Co-morbidities in childhood Barrett's esophagus.

PMID- 9285376
TI  - Inhibition of beta-glucuronidase by casein hydrolysate formula.
AB  - BACKGROUND: A casein hydrolysate infant formula has been shown to be associated
      with lower levels of neonatal jaundice than are standard infant formulas. Because
      beta-glucuronidase is related to neonatal jaundice, this study examined the
      effect of a casein hydrolysate formula on beta-glucuronidase. METHODS: Beta
      glucuronidase activity was measured with or without added dietary components. The
      beta-glucuronidase sources used were meconium, breast milk, and the purified
      bovine liver enzyme. The dietary components assayed for their effect on beta
      glucuronidase activity included casein hydrolysate formula (Nutramigen), whey
      predominant formula (Enfamil), breast milk; enzymatically hydrolyzed casein, and
      other constituents of the casein hydrolysate formula. Stool samples of 6-day-old
      infants, who were exclusively fed one of the two formulas or breast milk, were
      also assayed for inhibition of beta-glucuronidase. RESULTS: Only Nutramigen,
      enzymatically hydrolyzed casein, and stool from Nutramigen-fed infants
      consistently demonstrated significant inhibition of beta-glucuronidase activity,
      ranging from 45% to 85% of that in controls. The inhibition of beta-glucuronidase
      in purified bovine liver demonstrates a dose response in a pH range from 4 to
      7.3. CONCLUSIONS: Hydrolyzed casein contains a beta-glucuronidase inhibitor that,
      in casein hydrolysate-fed infants, persists after passage through the digestive
      tract. These data are consistent with the possibility that inhibition of beta
      glucuronidase is a mechanism by which infants fed casein hydrolysate have lower
      jaundice levels than infants fed routine formulas or breast milk. Further study
      of this mechanism is needed.

PMID- 9285375
TI  - Evaluation of intranasal midazolam in children undergoing
      esophagogastroduodenoscopy.
AB  - BACKGROUND: Intravenous midazolam and opioids are used to produce conscious
      sedation in children undergoing esophagogastroduodenoscopy (EGD). However,
      children may experience significant fear and anxiety before receiving these
      medications, especially during separation from parents and during venipuncture.
      Intranasal administration of midazolam represents a noninvasive method of
      sedating children before anxiety-producing events. The objective of this study
      was to determine whether premedication with intranasal midazolam reduces stress
      and anxiety of separation from parents and of undergoing venipuncture, while
      maintaining adequate sedation during EGD. METHODS: This was a prospective,
      randomized, double-blind study in 40 children, aged 2 to 12 years, who were
      undergoing EGD. Patients in group I were premedicated with intranasal placebo
      (0.9% NaCl) followed 10 minutes later by intravenous midazolam (0.05 mg/kg) and
      intravenous meperidine (1 mg/ kg). Patients in group II were premedicated with
      intranasal midazolam (0.2 mg/kg) followed by intravenous placebo (0.9% NaCl) and
      intravenous meperidine (1 mg/kg). Anxiolysis and sedation were scored by a
      blinded observer, who identified minor and major negative behaviors during four
      observation periods: intranasal drug administration, separation from parents,
      venipuncture, and EGD. RESULTS: Premedication with intranasal midazolam
      significantly reduced negative behaviors during separation from parents (p <
      0.05); however, no difference between regimens was noted during venipuncture or
      EGD. Negative behaviors appeared to increase during administration of intranasal
      midazolam or placebo. CONCLUSIONS: Premedication with intranasal midazolam is
      effective in reducing negative behaviors during separation from parents, while it
      maintains sedation during the endoscopic procedure. The benefits of intranasal
      administration may be negated, however, by irritation, and discomfort caused by
      intranasal drug delivery.

PMID- 9285377
TI  - Mucosal inflammation in pediatric diversion colitis: a quantitative analysis.
AB  - BACKGROUND: Diversion colitis commonly occurs in bypassed segments of colorectum,
      and has been described qualitatively in Hirschsprung's disease patients with
      colostomies. The objective of this study was to characterize quantitatively the
      changes in the inflammatory cell population in the mucosa of children with
      diversion colitis. METHODS: Paraffin blocks of well-oriented, full-thickness
      colorectal tissues were obtained from 15 children with diversion colitis (all
      with Hirschsprung's disease), four pediatric controls and four adult controls.
      Sections were immunostained for B and T lymphocytes, macrophages, IgG, IgM, and
      IgA. Measurements were made referent to a standard length of muscularis mucosae.
      Lymphoid follicles were counted and the areas occupied by B and T cells were
      determined by image analysis. Cells in the interfollicular lamina propria were
      counted separately, but IgA-containing plasma cells were too abundant to
      enumerate. RESULTS: Pediatric diversion colitis was characterized by enlarged and
      more numerous lymphoid follicles with approximately four times as many B
      lymphocytes and twice as many T lymphocytes in the follicular compartment of the
      mucosa when compared to pediatric controls. The interfollicular mucosa was
      thickened (499 +/- 27 versus 380 +/- 56 microns) and contained approximately six
      times as many B cells and eight times as many T cells as controls. Macrophages
      and plasma cells containing IgG and IgM were not significantly increased.
      CONCLUSIONS: These findings extend the qualitative observations of increased
      follicular and lamina propria lymphoid tissue in bypassed segments of colon, and
      are consistent with the hypothesis of persistent antigenic stimulation of the
      mucosa-associated lymphoid tissue.

PMID- 9285378
TI  - Pattern of metabolism and composition of the fecal microflora in infants 10 to 18
      months old from day care centers.
AB  - BACKGROUND: From 5 months of age, infants are progressively introduced to a
      variety of foods which influence the equilibrium of the intestinal microflora.
      METHODS: Thirty-five children age 10-18 months from 8 day care centers in France
      were studied. Fecal specimens were examined for their biochemical and
      microbiological criteria. RESULTS: Bifidobacteria and Bacteroides belong to the
      predominant populations (9.7 and 8.6 log 10 cfu/g, respectively). The mean level
      of enterobacteria and enterococci were 8.0 and 7.8 log 10 cfu/g, respectively.
      Only 10% of the infants presented a lactobacilli amount above 6 log 10 cfu/g.
      Most feces had similar pH values (mean 6.4), percentage of water (mean 76.4%),
      and short chain fatty acid, ammonia and lactic acid concentrations (means 77, 6.7
      and 2.3 mumol/g, respectively). beta-galactosidase had the highest activity (106
      IU/g of protein) and nitroreductase, the lowest (0.1 IU/g of protein). alpha
      glucosidase and nitrate reductase showed intermediate values of 17 and 4 IU/g of
      protein, respectively. With the exception of 4 infants, beta-glucosidase and beta
      glucuronidase values were low (4 and 2 IU/g of protein). Age and day care center
      were not significant factors for most parameters studied, except that rotavirus
      was related to day care center, with detection in 5 infants from the same center.
      CONCLUSIONS: Many biochemical parameters were comparable to those found in
      adults, with the exception of ammonia concentration and beta-galactosidase
      activity. The fecal bacterial profile was different than in adults, with more
      Bifidobacteria than Bacteroides and higher levels of facultative anaerobes. One
      infant suffering from gastroenteritis had distinctive biochemical and bacterial
      parameters.

PMID- 9285379
TI  - Intestinal permeability in cystic fibrosis in relation to genotype.
AB  - BACKGROUND: The purpose of this study was to investigate whether the increase
      intestinal permeability (IP) seen in patients with cystic fibrosis (CF) is
      correlated with the basic defect, as revealed by the patient's genotype, and/or
      whether the intestinal disturbance reflects secondary abnormalities such as
      essential fatty acid deficiency. METHODS: Nineteen CF patients were compared with
      nine age- and sex-matched healthy controls. IP was evaluated by studying urinary
      excretion for 5 hours after a test meal containing lactulose, L-rhamnose and
      xylose in water. Urine was analyzed for carbohydrates, and blood samples were
      taken for determination of the fatty acid pattern of serum phospholipids. The CF
      patients were grouped according to genotype: homozygous for delta F508,
      heterozygous for alpha F508, or unidentified. RESULTS: Patients who were
      homozygous (n = 9) or heterzygous (n = 6) for delta F508 had significantly higher
      lactulose/L-rhamnose excretion ratios (mean(range) values of 0.08(0.05-0.13) and
      0.09(0.03-0.13), respectively) than patients (n = 4) with unidentified genotypes
      [0.03(0.02-0.05); p = 0.005] or healthy controls [0.02(0.003-0.06); p = 0.002].
      CF patients with EFAD (n = 6) did not differ from those with a normal pattern of
      serum phospholipid fatty acids, the lactulose/L-rhamnose excretion ratio being
      0.08(0.02-0.13) and 0.07(0.03-0.12), respectively. CONCLUSIONS: These data show
      that the IP in CF was related to patient genotype; those homozygozous or
      heterozygous for delta F508 having a significantly increased IP compared with
      patients with unidentified genotypes, who had IP values within the normal range.

PMID- 9285380
TI  - Prevalence of lactose malabsorption in Galicia.
AB  - BACKGROUND: The aim of the current study was to evaluate the prevalence of
      lactose malabsorption (LM) in Galicia (NW Spain) in order to design nutritional
      intervention and/or public education strategies for high risk groups. METHODS: We
      conducted a study of LM by breath-hydrogen carbohydrate absorption test (BH2
      test) in 850 healthy subjects. All subjects underwent BH2 tests following
      ingestion of a aqueous solution of 2 g lactose/kg body weight up to a maximum of
      50 g. Subjects with LM were retested after ingesting 250 ml of milk and/or 250 ml
      of yogurt. RESULTS: The frequency of LM in the subjects who ingested 2 g
      lactose/kg body weight was 32.5%. This percentage decreased significantly with a
      decrease in the quantity of administered lactose and the vehicle was milk or
      yogurt-only 13.7% was LM after 250 ml of milk and 3.8% after 250 ml of yogurt.
      Gastrointestinal symptoms also depend on dosage of lactose and vehicle,
      decreasing from 54.3% after 2 g lactose/kg to 18.5% after milk and to 0% after
      yogurt. The frequency and number of gastrointestinal symptoms were significantly
      higher (p < 0.001) in LM than in lactose absorption (LA). CONCLUSIONS: Lactose
      malabsorption is prevalent in the population of Galicia. An important number of
      subjects identified as LM with usual clinical testing become LA when the
      ingestion of dairy products is limited so that the amount of lactose consumed is
      similar to that contained in a usual serving. Our results suggest the importance
      of BH2 testing following ingestion of usual consumed amounts of lactose per
      serving.

PMID- 9285381
TI  - The role of magnesium in the pathogenesis of bone disease in childhood
      cholestatic liver disease: a preliminary report.
AB  - BACKGROUND: Magnesium deficiency may contribute to the metabolic bone disease
      that complicates chronic cholestatic liver disease. We hypothesized that
      magnesium deficiency alters vitamin D metabolism by decreasing parathyroid
      hormone (PTH) response, resulting in decreased serum osteocalcin and decreased
      bone accretion. METHODS: Nine subjects, age 3-22 years, with cholestatic liver
      disease were evaluated with the magnesium retention test. The response of PTH,
      1,25(OH)2 vitamin D, and osteocalcin to provocative stimuli and dual x-ray
      absorptiometry measurement of bone mineral density (BMD) of the lumbar spine were
      assessed. Thereafter, subjects were treated with oral magnesium supplements.
      RESULTS: All nine subjects were magnesium depleted. Repletion with magnesium was
      successful in seven subjects, and required 4 to 31 (median 14) months with doses
      of 6 to 34 (median 11) mg/kg/day. Baseline serum PTH was significantly reduced in
      the cholestatic subjects compared to 15 age-matched controls. Comparison of
      baseline to repleted provocative testing was performed in six Mg-repleted
      subjects. Osteocalcin response increased significantly (p = 0.048) with
      repletion, while PTH response increased (p = 0.061). Lumbar spine BMD increased
      modestly with repletion (p = 0.093). CONCLUSIONS: This preliminary report
      suggests that magnesium depletion is extremely common in children with chronic
      cholestasis. We speculate that magnesium supplementation may be warranted to
      forestall the progression of metabolic bone disease in chronic cholestasis.

PMID- 9285382
TI  - Bound iron admixture prevents the spontaneous generation of peroxides in total
      parenteral nutrition solutions.
AB  - BACKGROUND: Parenteral administration of iron is a matter of controversy because
      it is feared that it could contribute to oxidative reactions. The aim of this
      study was to verify if irondextran participates in the redox reactions occurring
      in total parenteral nutrition (TPN) solutions. METHODS: Irondextran was compared
      with different forms of iron in the interaction with peroxides. Hydroperoxide
      levels were measured by a colorimetric technique in TPN solutions, in presence of
      varying sources (FeCl2, FeSO4, irondextran, iron sorbitol) and concentrations (0
      0.8 mM) of iron. The consumption and inhibition of peroxide generation were
      tested by analyzing the effect of iron on different sources of peroxides (H2O2,
      tert-butyl and cumen hydroperoxide). The free radicals produced under conditions
      of a Fenton-like reaction were measured by the oxidation of scopoletin. And the
      proportion of Fe3+ freed by both bound-iron sources was counted by measuring the
      masking effect on the thiol function of cysteine. RESULTS: Free-iron admixture to
      parenteral nutrition induces the formation of free radicals, whereas sources of
      bound-iron inhibit the generation of peroxides in parenteral nutrition without
      implying a Fenton-like reaction. CONCLUSION: For patients requiring iron
      supplementation, bound-iron should be added during the preparation of TPN
      solutions, because it protects against the spontaneous generation of peroxides.

PMID- 9285384
TI  - Ultrasound studies of the intestinal wall in patients with cystic fibrosis.
AB  - BACKGROUND: In 1994, first published reports described cystic fibrosis patients
      who experienced a then unknown complication-ileocecal and colonic stenoses with
      submucosal proliferation requiring surgical intervention. To investigate a
      suspected correlation between increased intestinal wall diameter and high doses
      of pancreatic enzymes, we carried out a prospective study in our CF-outpatient
      clinic. METHODS: By ultrasound analysis we measured the intestinal wall diameter
      in 201 patients. One hundred ninety-three patients treated with pancreatic
      enzymes had pancreatic insufficiency. Eight patients showed normal pancreatic
      function, seven of them had never been treated with pancreatic enzymes. The
      control group included 12 healthy children. Measuring points were the distal
      ileum, cecum, ascending, and descending colon. Measurements were made by the
      longitudinal and cross sectional cut. The following aspects of the patients'
      history were recorded (a) current type of pancreatic enzyme medication; (b) total
      dosage per day (with reference to lipase units); (c) duration of therapy with
      standard-strength pancreatic enzyme (SSPE) preparations (< or = 10,000 lipase
      units per capsule) and HSPE preparations (> or = 20,000 lipase units per
      capsule); (d) gastrointestinal complication (distal intestinal obstruction
      syndrome, meconium ileus, abdominal surgery, intussusception), diabetes mellitus,
      and hepatobiliary complications. RESULTS: The intestinal wall diameter in
      patients receiving HSPE therapy was greater (with prominent submucosal layer)
      than that in patients receiving SSPE therapy or in patients with pancreatic
      sufficiency. Healthy subjects had the smallest intestinal wall diameter. There
      was no correlation between patient history and increased intestinal wall
      thickness. CONCLUSIONS: Ultrasound detects characteristic ileocecal wall lesions
      in the majority of cystic fibrosis patients on pancreatic enzymes. These lesions
      may lead to significantly increased ileocecal wall thickness, which is correlated
      but not restricted to HSPE.

PMID- 9285383
TI  - Fecal bacterial enzyme activities in infants increase with age and adoption of
      adult-type diet.
AB  - BACKGROUND: The present study was conducted to determine the effects of age and
      diet (breast milk, milk formula, weaning diet) on the activities of some
      bacterial enzymes in fecal samples collected from 3- to 24-month-old infants.
      These bacterial enzymes may generate toxic, mutagenic, or carcinogenic
      metabolites from plant glycosides (beta-glucuronidase, beta-glucosidase) or from
      urea (urease). METHODS: The subjects were 68 healthy children ages 3 (n = 20), 6
      (n = 20), 12 (n = 17), and 24 (n = 11) months. None of the children had been
      given any antibiotics during 4 weeks before collection of the fecal samples.
      Health status, bowel habits, and food consumption of the children were determined
      by interview of one of the parents using a structured questionnaire. A spot fecal
      sample from each child was collected. RESULTS: The activities of beta
      glucuronidase and beta-glucosidase increased from 0.52 and 1.17 nmol/min x mg
      protein (at 3 months) to 1.41 and 2.38 nmol/min x mg protein (at 2 years),
      respectively. However, at 2 years of age, the children had not yet reached the
      levels reported in earlier studies on adult populations. Urease activity
      increased from 4.18 nmol/min x mg protein (at 3 months) to 19.0 nmol/min x mg
      protein (at 2 years), reaching by 12 months of age the level observed in adults.
      Breast feeding as such had no consistent effect on fecal bacterial enzyme
      activities. beta-Glucuronidase and beta-glucosidase were higher in those 6- and
      12-month-old children who consumed more meat, fish, sausages, or eggs.
      CONCLUSIONS: It can be concluded that the fecal enzyme activities in the
      gastrointestinal tract increase and that their profile changes with age and
      adoption of adult-type diet. It remains open, however, whether these changes are
      caused by the normal physiological aging process or by stepwise introduction of
      new foods to the diet.

PMID- 9285385
TI  - Abnormal bile acid metabolism and neonatal hemochromatosis: a subset with poor
      prognosis.
AB  - BACKGROUND: Inborn errors of bile acid synthesis are newly recognized disorders
      that may cause the phenotypic appearance of neonatal hepatitis or neonatal
      cholestasis. METHODS: This is a clinicopathologic study of two sets of siblings
      with cholestatic neonatal liver failure. RESULTS: In 3 of the infants, diagnostic
      evaluation, including analysis of urinary bile salts, revealed a predominance of
      7 alpha-hydroxy-3-oxo-4-cholenoic and 7 alpha, 12 alpha-dihydroxy-3-oxo-4
      cholenoic acids, a pattern consistent with delta 4-3-oxosteroid 5 beta-reductase
      deficiency, which could be primary or secondary. The fourth infant died before
      such testing could be carried out. In addition, all 4 infants had histologically
      disseminated hemochromatosis and met diagnostic criteria for neonatal
      hemochromatosis. In the 3 infants studied, histologic examination of the liver
      disclosed giant cell hepatitis with extensive loss of hepatic parenchyma and
      rapid progression to cirrhosis. Early treatment with ursodeoxycholic acid and
      cholic acid, previously reported as effective therapy, was given to 2 siblings;
      it failed to reverse or halt the liver damage, and both infants died. One infant,
      with the original diagnosis of neonatal hemochromatosis, was treated with a
      variety of antioxidants and chelation therapy, as recently reported. No
      improvement was demonstrated, and he went on to liver transplantation.
      CONCLUSIONS: The presentation of delta 4-3-oxosteroid 5 beta-reductase deficiency
      as neonatal hemochromatosis may represent a distinct subset of this disorder with
      an accelerated course, no response to therapy and poor prognosis.

PMID- 9285386
TI  - Growth hormone and glutamine do not stimulate intestinal adaptation following
      massive small bowel resection in the rat.
AB  - BACKGROUND: Certain nutrients and other trophic factors are highly sensitive
      stimulants of intestinal adaptation following short bowel syndrome. Growth
      hormone and glutamine in a modified diet have been shown to enhance nutrient
      absorption in patients with severe short bowel syndrome. However, neither growth
      hormone nor glutamine is capable of enhancing adaptation in an animal model. This
      study was conducted to determine if the combination of glutamine and growth
      hormone could enhance gut adaptation following massive small bowel resection in
      the rat. METHODS: Thirty-four male rats received 70% jejunoileal resection. The
      first group received glycine and rat growth hormone, the second glutamine and rat
      growth hormone, and the third glycine but no growth hormone. RESULTS: There was
      no evidence that the combination of glutamine and growth hormone could enhance
      mucosal mass, mucosal protein, or mucosal DNA levels relative to the other two
      control groups of animals. Likewise, sucrase activities were not enhanced by
      glutamine and growth hormone. CONCLUSIONS: It is unlikely that the combination of
      glutamine and growth hormone will be of benefit in the treatment of patients with
      short bowel syndrome. The results in previous human studies can be alternatively
      explained by the long-term nonspecific effect of enteral nutrition on gut
      adaptation.

PMID- 9285387
TI  - Spermine induces maturation of the immature intestinal immune system in neonatal
      mice.
AB  - BACKGROUND: In mice, immunological adaptation of the gut to microbial and
      nutritional antigens occurs at weaning in parallel with biochemical and
      morphological maturation. Because oral administration of spermine to neonatal
      rats has been shown to induce biochemical and morphological maturation, we
      investigated whether spermine also affects maturation of the mucosal immune
      system. METHODS: Swiss mice 7, 12, and 27 days old were given spermine orally
      (0.5 mumol/g body weight) during 3 days. Intestinal length was measured, and
      lactase and sucrase activities were determined. The phenotype of intraepithelial
      and lamina propria lymphocytes was assessed by FACS analysis using markers for
      CD3, TCR alpha beta, TCR gamma delta, CD4, CD8 alpha, CD8 beta, CD5, CD18, CD54,
      and CD49d. RESULTS: Similar to what occurs during natural development, spermine
      treatment of neonatal mice increased intestinal length, decreased lactase
      activity, and increased sucrase activity. The percentage of intraepithelial
      lymphocytes expressing TCR alpha beta, CD4, CD5, and CD54, as well as the levels
      of expression of these antigens, increased after spermine treatment on day 12,
      similarly to natural maturation. The increase in expression of CD3, TCR gamma
      delta, CD18, and CD49d did not reach statistical significance. No effect was
      observed on CD8 expression. The phenotype of lamina propria lymphocytes was not
      affected. Spermine administration to 7- and 27-day-old mice had no effect on the
      phenotype of either intraepithelial or lamina propria lymphocytes. CONCLUSIONS:
      Oral spermine administration to neonatal mice induced, in parallel with
      biochemical maturation, precocious maturation of the murine intestinal immune
      system and particularly affected differentiation of the intraepithelial
      lymphocyte population.

PMID- 9285388
TI  - Steroid-resistant lymphocytic enterocolitis and bronchitis responsive to 6
      mercaptopurine in an adolescent.

PMID- 9285389
TI  - Gastrocolic fistula in pediatric Crohn's disease.

PMID- 9285390
TI  - Two siblings with exocrine pancreatic hypoplasia and orofacial malformations
      (Donlan syndrome and Johanson-Blizzard syndrome).

PMID- 9285392
TI  - Internal abdominal hernias in childhood.

PMID- 9285391
TI  - Histopathologic features of the biopsied liver at onset of childhood B-precursor
      acute lymphoblastic leukemia presenting as severe jaundice.

PMID- 9285393
TI  - Zinc in the treatment of diarrhea.

PMID- 9285394
TI  - Maternal diarrhea and ischemic enteritis in newborn twins: possible association
      with an hemolytic uremic syndrome outbreak.

PMID- 9285395
TI  - IgA deficiency and coeliac disease.

PMID- 9285396
TI  - Celiac disease.

PMID- 9285397
TI  - Performance of time delay estimation methods for small time shifts in ultrasonic
      signals.
AB  - In this study several time delay estimation (TDE) methods were investigated for
      estimation of time shifts of less than 10 ns at a frequency of 30 MHz. Using
      simulated and experimental echosignals we investigated the performance of five
      methods: two phase related methods (phase shift and phase difference method); two
      correlation methods (cross-correlation and correlation interpolation method); and
      a demodulation method. The results showed that the correlation interpolation
      method is by far the most accurate for all time delays. With this method,
      estimation errors of about 200 ps are achievable with an signal-to-noise ratio
      (SNR) of 40 dB (f0 = 30 MHz, bandwidth = 20 MHz) for time shifts of up to 10 ns.

PMID- 9285398
TI  - Regional variations in suicide rates--United States, 1990-1994.
AB  - In 1994, suicides were committed by 31,142 persons in the United States (crude
      rate: 12.0 suicides per 100,000 population), and suicide was the ninth leading
      cause of death. Although rates of suicide have varied by geographic region (e.g.,
      rates have consistently been higher in western states, reasons for these regional
      variations are unknown but may reflect regional differences in certain
      demographic variables. For example, suicide rates have been higher for males, for
      the elderly, and for certain racial/ethnic groups (e.g., non-Hispanic whites and
      American Indians/Alaskan Natives). CDC examined U.S. suicide rates from 1990
      through 1994 to determine whether regional variations in suicide rates are
      affected by differences in age, race/Hispanic-ethnicity, and sex and to examine
      whether method-specific rates varied by region. This report summarizes the
      results of that analysis, which indicate that, despite adjustments for certain
      demographic variables, regional differences persist.

PMID- 9285399
TI  - Progress toward poliomyelitis eradication--Eastern Mediterranean Region, 1996
      1997.
AB  - In 1988, the Regional Committee of the Eastern Mediterranean Region (EMR) of the
      World Health Organization (WHO) adopted a resolution to eliminate poliomyelitis
      from the region by 2000. This report summarizes progress toward this goal in EMR
      countries through June 30, 1997, and indicates that nearly all countries in the
      EMR are conducting National Immunizations Days (NIDs) and that surveillance for
      acute flaccid paralysis (AFP) is improving rapidly.

PMID- 9285400
TI  - Multiple misdiagnoses of tuberculosis resulting from laboratory error--Wisconsin,
      1996.
AB  - A positive culture for Mycobacterium tuberculosis confirms a diagnosis of
      tuberculosis disease (TB); however, false-positive cultures have resulted from
      laboratory error. In 1996, the Division of Health (DOH), Wisconsin Department of
      Health and Family Services, became aware of five possible incidents of laboratory
      error associated with the processing of M. tuberculosis cultures; these incidents
      resulted in the potential misdiagnosis of TB in 11 persons. This report
      summarizes the findings from the investigation of the five incidents, which
      suggest that four incidents were associated with cross-contamination of specimens
      in the laboratory and one with the inadvertent inoculation of a subculture from
      the incorrect broth medium; these errors resulted in adverse effects on patients
      and on the medical and public health systems.

PMID- 9285401
TI  - Perceptions of child sexual abuse as a public health problem--Vermont, September
      1995.
AB  - CDC and the World Health Organization have declared violence prevention a public
      health priority. One particular form of violent victimization, child sexual
      abuse, is a risk factor for suicide attempts, depression, sexually transmitted
      diseases, and subsequent sexual assault. The public health approaches to child
      sexual abuse are intervention (e.g., treatment) and prevention. To assist in
      developing public health measures for preventing child sexual abuse in Vermont,
      in September 1995, STOP IT NOW! and Market Street Research, Inc., surveyed a
      representative sample of households in Vermont to assess knowledge and attitudes
      about child sexual abuse as a public health problem. This report summarizes the
      survey findings, which indicate that levels of awareness of child sexual abuse
      are high among Vermont residents.

PMID- 9285402
TI  - In thymic selection, peptide diversity gives and takes away.

PMID- 9285403
TI  - T cells can be activated by peptides that are unrelated in sequence to their
      selecting peptide.
AB  - We tested the ability of CD4+ T cells, selected in the thymus by reaction with
      class II protein bound to a single peptide, to react with the same class II
      protein bound to other peptides. The T cells reacted with all peptides tested,
      including one that was quite unlike the selecting peptide in T cell receptor
      binding residues. The receptors on class II/peptide-reactive T cells from class
      II/single peptide mice were similar but not identical to some of those from
      normal animals. Thus, class II bound to a single peptide selects a subset of T
      cells that is related to that selected by class II bound to many peptides.

PMID- 9285404
TI  - Selection of a broad repertoire of CD4+ T cells in H-2Ma0/0 mice.
AB  - According to past reports, H-2Ma0/0 mice express a single major histocompatiblity
      complex class II molecule, A(b), heavily loaded with a single peptide derived
      from the invariant chain, CLIP. Despite the highly restricted diversity of the
      class II:peptide complexes expressed on thymic stromal cells in the mutant
      animals, a large and diverse population of CD4+ T cells is positively selected.
      However, two important issues remained unresolved and are addressed here: Just
      how preponderant is CLIP occupancy of the class II molecules from H-2M0/0 mice?
      How extensive and functionally competent is the CD4+ population selected in the
      mutant animals? Our results argue that a single class II:peptide complex can
      select a very broad, though not complete, repertoire of CD4+ T cells.

PMID- 9285405
TI  - Deficient positive selection of CD4 T cells in mice displaying altered
      repertoires of MHC class II-bound self-peptides.
AB  - The role of self-peptides in positive selection of CD4+ T cells has been
      controversial. We show that some self-peptides are presented by the MHC class II
      molecule I-A(b) in mice lacking Ii or H-2M but not in mice expressing a transgene
      encoded peptide fused to I-A(b). In experiments using specific antibodies to
      block selection, these low-abundance self-peptides were implicated in the
      positive selection of some CD4+ T cells in H-2M-/- mice. However, all three
      mutant backgrounds failed to positively select two class II-restricted transgenic
      T cell receptors. Our findings suggest that minor components of the self-peptide
      repertoire can contribute to positive selection of a significant number of CD4+ T
      cells. In addition, the data suggest that T cell receptor repertoires selected in
      wild-type mice and in mice displaying limited spectra of self-peptides are
      distinct.

PMID- 9285406
TI  - Thymic selection by a single MHC/peptide ligand produces a semidiverse repertoire
      of CD4+ T cells.
AB  - The influence of individual peptides in thymic selection was examined in H2-M-
      mice, in which positive selection is directed to a single peptide, class II
      associated invariant chain peptide (CLIP) bound to H2-A(b). Two sensitive in vivo
      approaches showed that 70%-80% of CD4+ T cells undergoing positive selection to
      CLIP+H2-A(b) have self-reactivity to the various peptides expressed on wild-type
      H2-M+ antigen-presenting cells. When these self-reactive T cells were depleted,
      the residual CD4+ cells displayed a polyclonal repertoire in terms of
      alloreactivity, responses to foreign protein antigens, and Vbeta usage.
      Nevertheless, studies with two T cell receptor transgenic lines suggested that
      the repertoire of CD4+ cells induced by CLIP was less diverse than the repertoire
      of CD4+ cells in normal mice. Generation of a fully diverse T cell repertoire
      thus requires positive selection against multiple peptides.

PMID- 9285407
TI  - Specific recognition of thymic self-peptides induces the positive selection of
      cytotoxic T lymphocytes.
AB  - To understand how thymic selection gives rise to T cells that are capable of
      major histocompatibility complex (MHC)-restricted recognition of antigen but are
      tolerant of self, we directly examined how peptide/MHC ligands expressed on
      thymic epithelial cells trigger the positive selection of immature thymocytes. We
      demonstrate that abundant self-peptides, purified from the H-2D(b) molecules of
      thymic epithelial cells, are specifically recognized during the positive
      selection of CD8+ T cells, implying that positive selection generates a
      repertoire of T cells that is weakly self-reactive. We also found that this
      recognition is somewhat cross-reactive, thereby providing an explanation for how
      the specific recognition of a limited repertoire of thymic self-peptides can
      select a diverse repertoire of T cells.

PMID- 9285408
TI  - Quantitation of the cell surface level of Ld resulting in positive versus
      negative selection of the 2C transgenic T cell receptor in vivo.
AB  - The 2C transgenic TCR is positively selected on Kb and is alloreactive for and
      negatively selected on Ld. To test an avidity model for positive selection, mice
      were bred to express different levels of surface Ld by varying the number of gene
      copies encoding beta 2-microglobulin (beta 2m) or Ld heavy chain. Whereas mice
      expressing 35% Ld (beta 2m+/- Ld+/-) negatively selected the 2C TCR, mice
      expressing 2% Ld (beta 2m-/- Ld+/-) positively selected the 2C TCR. Furthermore,
      2C cytotoxic T lymphocytes selected on 2% Ld showed peptide-specific cytolytic
      activity against Ld/p2Ca targets. These findings provide clear in vivo evidence
      that positive selection can occur on very low levels of the same class I antigen
      capable of negative selection when expressed at higher levels.

PMID- 9285409
TI  - The interferon regulatory transcription factor IRF-1 controls positive and
      negative selection of CD8+ thymocytes.
AB  - Little is known about the molecular mechanisms and transcriptional regulation
      that govern T cell selection processes and the differentiation of CD4+ and CD8+ T
      cells. Mice lacking the interferon regulatory transcription factor-1 (IRF-1) have
      reduced numbers of mature CD8+ cells within the thymus and peripheral lymphatic
      organs. Here we show that positive and negative T cell selection of two MHC class
      I-restricted TCR alphabeta transgenes, H-Y and P14, are impaired in IRF-1-/-
      mice. The absence of IRF-1 resulted in decreased expression of LMP2, TAP1, and
      MHC class I on thymic stromal cells. Despite decreased MHC class I expression on
      IRF-1-/- thymic stromal cells, the defect in CD8+ T cells development did not
      reside in the thymic environment, and IRF-1-/- stromal cells can fully support
      development of CD8+ thymocytes in in vivo bone marrow chimeras and in vitro
      reaggregation cultures. Moreover, IRF-1-/- thymocytes displayed impaired TCR
      mediated signal transduction, and the induction of negative selection in TCR Tg
      thymocytes from IRF-1-/- mice required a 1000-fold increase in selecting peptide.
      We also provide evidence that IRF-1 is mainly expressed in mature, but not
      immature, thymocytes and that expression of IRF-1 in immature thymocytes is
      induced after peptide-specific TCR activation. These results indicate that IRF-1
      regulates gene expression in developing thymocytes required for lineage
      commitment and selection of CD8+ thymocytes.

PMID- 9285410
TI  - A range of CD4 T cell tolerance: partial inactivation to organ-specific antigen
      allows nondestructive thyroiditis or insulitis.
AB  - T cell receptor (TCR) transgenic mice specific for hen egg lysozyme (HEL) were
      crossed with mice expressing HEL on the thyroid epithelium, on pancreatic islet
      beta cells, or systemically. Depending on the pattern of HEL expression, deletion
      of double-positive thymocytes ranged from minimal to complete, and peripheral CD4
      cells exhibited graded reduction in TCR expression, in vitro responsiveness, and
      in vivo helper ability. CD4 cells were least tolerant in TCR/thyroid-HEL and
      TCR/islet-HEL mice, which developed an extensive lymphocytic thyroiditis or
      insulitis that nevertheless did not eliminate HEL-expressing endocrine cells.
      Autoreactive CD4 clones thus escape the thymus under a range of circumstances,
      retain sufficient function to initiate subclinical autoimmune inflammation when
      self-antigens are concentrated in the thyroid or pancreas, and may regulate
      progression of subclinical inflammation to destructive autoimmune disease.

PMID- 9285411
TI  - A novel immunoglobulin superfamily receptor for cellular and viral MHC class I
      molecules.
AB  - The human cytomegalovirus UL18 gene product is a homolog of cellular major
      histocompatibility (MHC) class I antigens. UL18 has been proposed to protect
      virus-infected cells against natural killer (NK) cell cytotoxicity by engaging NK
      cell killer inhibitory receptors (KIR) for MHC class I. UL18 binds to a novel
      immunoglobulin superfamily glycoprotein, designated Leukocyte Immunoglobulin-like
      Receptor (LIR-1). This protein is distinct from, but related to, known KIRs and
      binds cellular MHC class I antigens. The cytoplasmic domain of LIR-1 contains
      four putative immunoreceptor tyrosine-based inhibitory motifs. Upon tyrosine
      phosphorylation, LIR-1 associates with the tyrosine phosphatase SHP-1. In
      contrast to KIRs, LIR-1 is expressed predominantly on monocytic and B lymphoid
      cell types, suggesting a distinct biological function.

PMID- 9285412
TI  - LAIR-1, a novel inhibitory receptor expressed on human mononuclear leukocytes.
AB  - In the present study, we describe a novel inhibitory receptor, leukocyte
      associated immunoglobulin-like receptor-1 (LAIR-1), that is constitutively
      expressed on the majority of human peripheral blood mononuclear leukocytes. LAIR
      1 is a 32 kDa transmembrane glycoprotein with a single immunoglobulin-like domain
      and a cytoplasmic tail containing two immune receptor tyrosine-based inhibitory
      motifs. LAIR-1 recruits SHP-1 and SHP-2 phosphatases upon activation, and cross
      linking of the LAIR-1 antigen on natural killer (NK) cells results in strong
      inhibition of NK cell-mediated cytotoxicity. Although it is structurally related
      to human killer cell inhibitory receptors, LAIR-1 does not appear to recognize
      human leukocyte antigen (HLA) class I molecules and thus represents a novel HLA
      class I-independent mechanism of NK cell regulation.

PMID- 9285414
TI  - Coding joint formation in a cell-free V(D)J recombination system.
AB  - V(D)J recombination assembles the variable portion of antigen receptor genes in
      developing lymphocytes and is the only site-specific recombination reaction known
      in vertebrates. A cell-free system has been established that performs DNA
      cleavage, end processing, and joining to yield V(D)J coding joints that exhibit
      structural features similar to those formed in vivo. The reaction has the
      expected substrate, metal ion, and RAG protein requirements. The efficiency of
      coding joint formation is reduced dramatically by uncoupling the cleavage and
      joining portions of the reaction, indicating that a postcleavage coding end
      complex facilitates joining. By varying the reaction conditions, nucleotide loss
      from coding ends and heterogeneity of coding joints can be regulated. This cell
      free system provides a novel tool for detailed mechanistic analyses of the end
      processing and joining steps of V(D)J recombination.

PMID- 9285413
TI  - TECK: a novel CC chemokine specifically expressed by thymic dendritic cells and
      potentially involved in T cell development.
AB  - A novel CC chemokine was identified in the thymus of mouse and human and was
      designated TECK (thymus-expressed chemokine). TECK has weak homology to other CC
      chemokines and maps to mouse chromosome 8. Besides the thymus, mRNA encoding TECK
      was detected at substantial levels in the small intestine and at low levels in
      the liver. The source of TECK in the thymus was determined to be thymic dendritic
      cells; in contrast, bone marrow-derived dendritic cells do not express TECK. The
      murine TECK recombinant protein showed chemotactic activity for activated
      macrophages, dendritic cells, and thymocytes. We conclude that TECK represents a
      novel thymic dendritic cell-specific CC chemokine that is possibly involved in T
      cell development.

PMID- 9285415
TI  - Contrast media-induced nephrotoxicity: a new insight.

PMID- 9285416
TI  - Spiral computed tomography and pulmonary embolism: current state.

PMID- 9285417
TI  - Pictorial review: magnetic resonance imaging of the paediatric elbow.

PMID- 9285418
TI  - MR imaging of soft tissues adjacent to orthopaedic hardware: techniques to
      minimize susceptibility artefact.
AB  - This article demonstrates and compares imaging of orthopaedic hardware (fixation
      plates, screws, Kischner wire and prostheses) using gradient-echo, spin-echo and
      fast spin-echo sequences. It describes simple techniques which minimize
      susceptibility artefact induced by these components at magnetic resonance (MR)
      imaging, allowing visualization of adjacent soft tissues. The article emphasizes
      the importance of selecting the appropriate imaging plane in order to avoid
      hardware distortion of slice select gradients, emphasizes the importance of
      selecting frequency encoding gradient axes in order to orientate the long axis of
      the artefact away from the tissue of interest and, finally, compares the marked
      susceptibility artefact observed adjacent to hardware using gradient-echo with
      the artefact reduction achieved by using fast spin-echo sequences.

PMID- 9285419
TI  - MR angiography and MR imaging of symptomatic vascular malformations.
AB  - PURPOSE: To define the appearance of peripheral vascular malformations at
      magnetic resonance angiography (MRA) and assess the role of magnetic resonance
      imaging (MRI) and MRA in the investigation of these lesions. PATIENTS AND
      METHODS: Fourteen patients (aged 8-51 years) with clinical evidence of a vascular
      malformation were referred for MRI and MRA, performed on a 0.5T GE Vectra
      superconducting system (International General Electric, Slough, UK). Multisection
      T1-weighted spin-echo and T2-weighted fast spin-echo pulse sequences were
      performed, with an inversion recovery fast spin-echo sequence in two cases. Two
      dimensional time of flight (2-D TOF) and/or 2-D phase contrast (PC) MRA was
      performed in 13 cases. Eleven patients had digital subtraction angiography (DSA)
      using a Phillips Integris V3000 digital angiographic unit. The findings at MRA
      and MRI were compared with the catheter angiograms, and the effective diagnostic
      input of MRA and MRI was determined. RESULTS: MRA demonstrated major feeding
      vessels and multiple intra-lesional vessels in relation to the high flow lesions,
      features absent in the low flow lesions. However, small feeding vessels to the
      AVMs were not clearly identified. MRI gave a clear demonstration of the
      anatomical extent of all lesions. AVMs (n = 6) and venous malformations (n = 6)
      were reliably distinguished, the former containing multiple serpentine signal
      voids on T1- and T2-weighted imaging, the latter being hyperintense to fat on T2
      weighted images. Two other high-flow lesions diagnosed clinically as vascular
      malformations appeared solid on MRI, and were diagnosed histologically as a
      carotid body tumour and an angiomyolipoma. CONCLUSION: Although 2-D TOF MRA can
      distinguish AVMs from venous malformations, the technique adds little extra
      practical information to the diagnostic process, and cannot compete with catheter
      angiography for the detailed demonstration of AVM feeding vessels. These lesions
      can also be characterized using spin-echo sequences, though the primary role of
      MRI is to demonstrate their anatomical extent.

PMID- 9285420
TI  - MR differentiation of phaeochromocytoma from other adrenal lesions based on
      qualitative analysis of T2 relaxation times.
AB  - AIM: To determine the diagnostic accuracy of MR imaging in differentiating
      phaeochromocytoma from other adrenal lesions. MATERIALS AND METHODS: Sixty-seven
      adrenal masses (65 patients) including 17 phaeochromocytomas were imaged using T2
      weighted pulse sequences on 0.6 T and 1.5 T GE MR units. The adrenal lesions were
      qualitatively assessed by three observers and divided into three categories
      (benign adenomas, malignant lesions and phaeochromocytomas) based on lesion
      signal intensity relative to liver and cerebrospinal fluid. RESULTS: Eleven
      phaeochromocytomas (65%) were correctly identified while the remaining six (35%)
      were misclassified, five as malignant lesions and one as a benign adenoma,
      because of atypical low signal intensity on T2-weighted MR images. Conversely,
      six non-phaeochromocytomas (three benign adenomas, two adrenal carcinomas and one
      metastasis) were wrongly classified as phaeochromocytomas because of very high
      lesion signal intensity. The sensitivity of MR imaging for diagnosing
      phaeochromocytoma was 64.7%, specificity 88.0%, positive predictive value 64.7%
      and negative predictive value 88.0%. CONCLUSION: There is considerable overlap
      between the MR appearance of phaeochromocytoma and other adrenal lesions. A
      phaeochromocytoma cannot be excluded on the basis of a lack of high signal
      intensity on T2-weighted MR imaging.

PMID- 9285421
TI  - Avascular necrosis of bone following an intensified chemotherapy regimen
      including high dose steroids.
AB  - We report the imaging findings and natural history of avascular necrosis of bone
      (AVN) that developed following a chemotherapy regimen including high dose steroid
      treatment. All patients had acute lymphoblastic (ALL) or non-Hodgkin's lymphoma
      (NHL). Symptoms followed the high dose steroid therapy and 28 joints in eight
      patients were involved, (11 knees, seven hips, five shoulders and five ankles).
      Plain radiographs at presentation were normal in most joints, whilst bone
      scintigraphy and magnetic resonance imaging (MRI) were positive. We believe that
      the development of AVN in these patients is most likely due to the high dose
      dexamethasone therapy as in all eight cases symptoms followed this stage of the
      regimen. Patients experiencing bone or joint pains while receiving high dose
      steroids as part of a chemotherapy regimen could be investigated by bone
      scintigraphy but MRI is preferable as it is more sensitive and specific for AVN.
      In this series of patients multiple joints were involved and all the male
      patients proceeded rapidly from bone infarction to joint collapse. If the MRI
      appearances are typical, an early diagnosis of AVN can be made enabling
      therapeutic interventions to prevent joint collapse and its associated morbidity.

PMID- 9285422
TI  - The radiological appearances after the endoscopic crico-pharyngeal myotomy:
      Dohlman's procedure.
AB  - The treatment of pharyngeal pouches (Zenker's Diverticulum) may be by either open
      surgical or endoscopic techniques. The endoscopic Dohlman's procedure is an ideal
      technique in the elderly. However, confusion has been created by the persisting
      presence of the pouch on the postoperative barium examination, creating the
      impression of surgical failure. We describe the subtle radiographic findings of
      the postoperative barium swallow by comparing pre- and postoperative examinations
      which may be used to indicate the success of the procedure. These include
      demonstration of the reduced height of the partition wall, the ease of passage of
      the barium down the ooesophagus and the height of barium supported in the
      substance of the residual pouch.

PMID- 9285423
TI  - Stripping of failing haemodialysis catheters using the Ampltaz gooseneck snare.
AB  - The development of a fibrin sheath at the tip of a long-term haemodialysis
      catheter may lead to deteriorating blood flow rates, resulting in inadequate
      haemodialysis. Restoration of functional patency has been described using the
      technique of percutaneous fibrin sheath stripping (PFSS) using a wire snare
      device. Our purpose was to assess this technique within an established renal
      vascular access service. All catheters referred for the assessment of low blood
      flow rates on dialysis were considered for the procedure. Initial fluoroscopic
      assessment of the catheter was followed by stripping of the tip of the catheter
      using a gooseneck snare. Seventeen of 22 well-positioned catheters undergoing a
      single PFSS attempt were restored to function with a median prolongation of
      patency of 4.25 months. Two catheters underwent a second PFSS procedure providing
      additional patency. Nineteen of a total of 24 (79%) PFSS procedures successfully
      restored catheter function. Seven catheters with poorly positioned tips or a kink
      were not restored to functional patency using PFSS. Two patients developed a
      puncture site haematoma. No patient developed symptoms of pulmonary emoblism. In
      conclusion, PFSS restored function in 79% of attempts in well positioned
      catheters. The method is technically straightforward, with a low complication
      rate and has become a routine part of the renal vascular access service.

PMID- 9285424
TI  - Technical report: an alternative mechanical technique of pseudoaneurysm
      compression therapy.
AB  - Graded manual compression therapy under ultrasound guidance has become the
      standard first line treatment of post-catheterization femoral pseudoaneurysms.
      Although effective, this treatment is often poorly tolerated by both patient and
      operator. We describe a new mechanical technique which has proven successful in
      our department, and is well tolerated by both patients and staff.

PMID- 9285425
TI  - The radiological investigation of suspected lower limb deep vein thrombosis.
AB  - A postal survey was performed to determine the current practices and attitudes of
      radiologists towards the imaging of suspected lower limb deep vein thrombosis
      (DVT). One hundred and twenty-seven departments responded to a questionnaire sent
      in March 1996. The results show that 87% of hospitals possess colour Doppler
      ultrasound (CDUS) machines and that 46% of departments perform ultrasound as the
      first line investigation in over 90% of cases. Thirty per cent of departments
      considered calf vein visualization to be generally adequate and 34% thought that
      clinicians in their hospitals invariably anticoagulated patients with isolated
      calf thrombus. In hospitals where venography was routinely used as the first line
      investigation, the most common reasons were: the perceived inferiority of
      ultrasound (US) in demonstrating below-knee clot, its time-consuming nature and
      the limited access to suitable ultrasound machines. The widespread use of
      ultrasound is encouraging, however, there are clearly diverse views. A
      significant minority of departments depend principally upon venography in the
      diagnosis of DVT.

PMID- 9285426
TI  - Case report: delayed superficial femoral artery pseudoaneurysm rupture following
      successful compression therapy.

PMID- 9285427
TI  - Case report: focal fatty liver infiltration causing mass effect.

PMID- 9285428
TI  - Case report: early structural failure of an Antheor inferior vena caval filter.

PMID- 9285429
TI  - Case report: palliative treatment of a rectal tumour with a self-expanding
      metallic stent.

PMID- 9285430
TI  - An additional approach to percutaneous ureteric stenting in difficult strictures.

PMID- 9285432
TI  - Exotic perspectives and salient cases.

PMID- 9285431
TI  - Accuracy and observer variation.

PMID- 9285433
TI  - Developmental outcomes in children receiving resection surgery for medically
      intractable infantile spasms.
AB  - Two-year postsurgical developmental outcomes were assessed in 24 children with
      infantile spasms who underwent resective surgery. The mean age of onset of
      infantile spasms was 12.0 weeks and the mean age at surgery was 20.8 months.
      Developmental outcomes were assessed using the Vineland Adaptive Behavior Scales
      (VABS). There was a significant increase in developmental level at 2 years
      postsurgery compared with presurgical levels. At 2 years postsurgery only one of
      the children in this series was severely retarded. The developmental outcomes of
      patients in the series were better than those in prior studies of symptomatic
      patients receiving medical treatment for infantile spasms. It is surprising that
      the children in the UCLA series frequently had developmental outcomes equal to
      and sometimes superior to other groups of children with infantile spasms, since
      all the UCLA patients were symptomatic, had neurologic deficits and had failed to
      respond to adrenocorticotrophic hormone (ACTH) and antiepileptic drugs. The 2
      year postsurgery developmental outcomes were best for the children who received
      surgery when they were relatively young and who had the highest level of
      developmental attainments presurgically.

PMID- 9285434
TI  - Severity of brain injury following neonatal extracorporeal membrane oxygenation
      and outcome at age 5 years.
AB  - Neurodevelopmental evaluation in childhood provides an opportunity to study
      complex neurological compensation following documented neonatal brain injury, and
      furnishes important clinical information which may have an impact on patient
      care. We studied 152 term children treated with extracorporeal membrane
      oxygenation (ECMO) as neonates and who received routine neonatal neuroimaging and
      comprehensive neurodevelopmental evaluation at age 5 years. The cohort was
      divided into four groups based on an independent neuroimaging score: No lesion,
      N=88; Mild lesion, N=38; Moderate lesion, N=12; and Severe lesion, N=14.
      Standardized testing at age 5 included complete neuropsychological assessment,
      neurological evaluation, and assessment of motor function. All testing was
      conducted without knowledge of the neuroimaging score. The occurrence of
      disability by severity of neuroimaging was: No lesion=10%; Mild=13%;
      Moderate=33%; Severe=57%. The relative risk within the ECMO population for
      disability at age 5 after moderate or severe neonatal lesion was 4.3 (CI=1.0 to
      17.5) and 11.7 (CI=3.3 to 41.3), respectively. The remaining non-disabled
      children who had moderate to severe lesions functioned within normal limits.
      Severity of neonatal neuroimaging was inversely associated with IQ scores, pre
      academic skills, and neuromotor function. The effect size was small but the rank
      order was predictable. Our data identify in 5-year-old children an impact of
      brain lesion severity demonstrated on routine neonatal neuroimaging. The results
      indicate potential compensation following moderate and severe lesions, and
      suggest a subtle but consistent influence of even mild neonatal brain injury.

PMID- 9285436
TI  - EEG and evoked potentials in infantile neuronal ceroid-lipofuscinosis.
AB  - Sixteen children with infantile neuronal ceroid-lipofuscinosis (INCL), age range
      0.5 to 5.4 years, were studied using EEG, electroretinograms (ERG), visual evoked
      potentials (VEP) and somatosensory evoked potentials (SEP).
      Electroencephalography was the first of these examinations to reveal
      abnormalities, however the EEG may be normal at the preclinical stage. The first
      abnormality to appear was an attenuated reaction to passive eye opening and
      closing which was followed by disturbances in background activity and diminution
      in amplitude, and by disappearance of sleep spindles. The gradual disappearance
      of posterior rhythm reactivity and of sleep spindles suggests that thalamic
      dysfunction progresses with time. EEG inactivity appeared by the age of 3 years.
      Evoked potentials were normal in the early stages of the disease. SEP showed
      abnormalities at Stage 2 (1.7 years), while ERG and VEP abnormalities appeared at
      Stage 3 (by the age of 2.5 years). All neurophysiological reactions examined were
      abolished by the age of 4 years. Follow-up EEG gives important hints as to the
      early diagnosis of INCL. Progression of the disease can be followed by evoked
      potentials which may also be helpful in the differential diagnostics.

PMID- 9285435
TI  - The importance of prenatal factors in childhood blindness in India.
AB  - The causes of visual loss in 1411 children attending schools for the blind in
      different geographical areas in India are described. Ninety-three percent (1318)
      of the children were severely visually impaired (SVI) or blind (i.e. corrected
      acuity in the better eye of <20/200 [<6/60]). In 60% of SVI/blind children vision
      loss was attributable to factors operating in the prenatal period, in 47% the
      prenatal factors were known and definite, and in 13% prenatal factors were the
      most probable causes. Hereditary retinal dystrophies and albinism were seen in
      19% of SVI/blind children and 23% had congenital ocular anomalies. There were
      variations in the relative importance of different causes by state. The observed
      pattern of causes of visual loss is intermediate between those seen in
      industrialised countries and in the poorest developing countries. This suggests
      that strategies to combat childhood blindness in India need to address
      concurrently both preventable and treatable causes. The need for aetiological
      studies, particularly on anophthalmos and microphthalmos, is highlighted.

PMID- 9285438
TI  - Soleus muscle length, stretch reflex excitability, and the contractile properties
      of muscle in children and adults: a study of the functional joint angle.
AB  - The influence of the joint angle on stretch reflex excitability of the soleus
      muscle at the ankle has been studied in 22 children aged 3.9 to 13.6 years and 9
      adults aged 19 to 70 years. For all subjects, reflex EMG and mechanical twitch
      torque gain were trivial at resting plantar flexion. The reflex EMG gain reached
      a maximum between -15 degrees and -10 degrees of plantar flexion beyond the
      neutral angle, 0 degrees, defined as the foot at right angle to the tibia,
      diminishing steeply with further dorsiflexion. The reflex mechanical gain rose to
      a peak between 0 degrees and +10 degrees of dorsiflexion beyond neutral,
      declining steeply thereafter. By contrast, axonally stimulated muscle twitch
      torque increased serially up to +30 degrees dorsiflexion beyond neutral. For the
      soleus muscle, the optimal reflex neuromechanical angle lies approximately midway
      between the angle for optimal reflex EMG gain (in mild plantar flexion, at which
      the largest and strongest motor units can be activated) and the optimal muscle
      mechanical angle (at the extreme of soleus muscle dorsiflexion). These studies
      confirm that the excitability of the spinal alpha motor neuron pool in vivo is
      strongly influenced by muscle length and explain the variability in reflex
      excitability within and between subjects, if the joint angle is not controlled.
      They also indicate how posture influences movement, agreeing with the known
      function of the soleus muscle in the stance phase of gait and the modulation of
      motor unit recruitment during voluntary alternating movements at the ankle.
      Soleus muscle twitch characteristics show a fivefold to eightfold increase in
      peak force associated with a tenfold reduction in compliance in the first two
      decades of life and an apparent speeding up of twitch time in the first decade.

PMID- 9285437
TI  - Somatosensory functioning in children with attention deficit hyperactivity
      disorder.
AB  - In order to test the hypothesis that attention deficit hyperactivity disorder
      (ADHD) is related to deficits in somatosensory processing, 49 ADHD male children
      and 49 matched controls were tested on a wide range of tactile tasks, and
      somatosensory evoked potentials (SEP) were also recorded. In addition, parents'
      and teachers' ratings on the children's typical responses to tactile stimuli were
      obtained. The results show that the ADHD children were less skilled on
      suprathreshold, but not on threshold tasks than were the controls. Further, a
      larger percentage of ADHD children were 'tactile defensive'. Finally, the ADHD
      children showed larger-than-normal amplitudes of late, but not early components
      of the SEP. These data suggest that some aspects of somatosensory processing by
      ADHD children are deficient.

PMID- 9285439
TI  - The epidemiology and clinical manifestations of hamstring muscle and plantar foot
      flexor shortening.
AB  - A population of 920 healthy children was studied with the aim of assessing the
      incidence of hamstring muscle and plantar foot flexor tightness, and to correlate
      such symptoms with gait, posture, and low back discomfort or pain. Special
      attention was paid to the popliteal angle and dorsal foot flexion. The borderline
      values for the popliteal angle in the following age groups were, boys: 3 to 5
      years, 40 degrees; 6 to 15 years, 50 degrees; and 16 to 19 years, 40 degrees;
      girls: 3 to 5 years, 30 degrees; 6 to 14 years, 45 degrees; 15 to 19 years, 30
      degrees. The borderline values for dorsal foot flexion in the following age
      groups were 3 to 4 years, 7 degrees; 5 to 13 years, 10 degrees; and 14 to 19
      years, 5 degrees. The results obtained indicate a natural increase in hamstring
      tightness, particularly shortly before the pubertal growth spurt. This seems to
      be linked with the natural evolution of lumbar lordosis and pelvic tilt. When
      hamstring tightness surpassed borderline values, dorsiflexion and lumbar lordosis
      decreased leading to postural deformities, bending-forward deficit, discomfort
      when sitting, and a shambling gait.

PMID- 9285440
TI  - Progressive facial hemiatrophy: MRI appearances.
AB  - The cranial CT and MRI appearances of a 14-year-old girl with Parry-Romberg
      syndrome and epilepsy are described. The findings are compared with the two
      published descriptions of MRI and CT in such patients. MRI appearances in our
      patient differ from those published and may be consistent with a vascular
      malformation. The one published report on the intracranial histopathology of a
      patient with Parry-Romberg syndrome and epilepsy states that a microscopic
      vascular malformation was found. We discuss the relationship between radiological
      and pathological findings. The possible aetiologies of Parry-Romberg syndrome
      (vascular malformation, immunological, trauma, sympathetic innervation,
      hereditary, slow virus) are discussed. We suggest that Parry-Romberg syndrome
      could be regarded as a neurocutaneous syndrome, a component of which includes
      intracerebral vascular dysplasia. In this and the other three cases of Parry
      Romberg syndrome with epilepsy, the sensitivity of MRI in detecting intracranial
      lesions is demonstrated. Recommendations for imaging these patients are proposed.

PMID- 9285441
TI  - Kabuki make-up (Niikawa-Kuroki) syndrome: cognitive abilities and autistic
      features.
AB  - Kabuki make-up syndrome (KMS), also known as Niikawa-Kuroki syndrome, is a rare
      malformation complex characterized by a peculiar facies with long palpebral
      fissures and partially everted lower eyelid, mental retardation, dwarfism, and
      skeletal and dermatoglyphic abnormalities. Four children from different ethnic
      groups presented with phenotypic manifestation of KMS. They showed variable
      degrees of learning disabilities, mental retardation, and autistic behavior. Two
      boys declined in IQ in early adolescence. In addition to being aware of the
      variable presentation of cognitive and behavioral characteristics in those
      already diagnosed, it is important to consider KMS when assessing dysmorphic
      children with learning disabilities and/or autism.

PMID- 9285442
TI  - 'Visual evoked potentials: a diagnostic test for migraine headache in children'.

PMID- 9285443
TI  - 'Botulinum toxin A in the hemiplegic upper limb: a double-blind trial'.

PMID- 9285444
TI  - 'Cognition in LND: a two-year follow-up study'.

PMID- 9285445
TI  - Paraneoplastic encephalomyelitis: an update of the effects of the anti-Hu immune
      response on the nervous system and tumour.

PMID- 9285447
TI  - Neurological picture. Gardner's hypothesis and magnetic resonance imaging.

PMID- 9285446
TI  - Effectiveness of psychological interventions for people with poorly controlled
      epilepsy.

PMID- 9285448
TI  - Neurological picture. Mimetic smile.

PMID- 9285449
TI  - Assessment of olfaction in multiple sclerosis: evidence of dysfunction by
      olfactory evoked response and identification tests.
AB  - OBJECTIVE: To resolve whether the olfactory pathways are affected in multiple
      sclerosis. METHODS: Olfaction was assessed by: (1) The University of Pennsylvania
      smell identification test (UPSIT, which uses microencapsulated odours that are
      released when scratched with a pencil) in 72 patients with multiple sclerosis and
      96 controls, (2) olfactory evoked potentials (OEP) to 20 ppm H2S by volume, and
      50% CO2 in air for 45 patients with multiple sclerosis and 47 controls. The
      abnormality rate in patients with multiple sclerosis for both tests (1) and (2)
      was compared with that for visual evoked potentials measured using a standard
      checquerboard technique. RESULTS: By comparison with controls, patients exhibited
      significantly low scores on the smell identification test with 15% of patients
      scoring outside the 95% confidence intervals for controls. The UPSIT was
      occasionally abnormal when the visual evoked potential (VEP) was normal. In
      general UPSIT scores correlated well with the H2S-evoked response in controls and
      patients. For H2S, there was a statistically significant increase of latency and
      decrease of amplitude for patients compared with controls. Increased H2S latency
      and reduced UPSIT score correlated with greater disability on conventional rating
      scales. Overall, H2S responses were abnormal in about one quarter of patients
      with multiple sclerosis. The sensitivity of UPSIT and OEP was similar although
      disorder on one test did not necessarily indicate abnormality in the other. The
      visual evoked potential was found to be a more sensitive indicator of disease
      than OEP or UPSIT. CONCLUSION: These findings confirm the existence of olfactory
      dysfunction in multiple sclerosis and validate a new evoked potential technique.

PMID- 9285451
TI  - Left-right differences in motor thresholds after stimulation of the globus
      pallidus before pallidotomy.
AB  - Left-right upper limb motor threshold differences were found after electrical
      stimulation of the globus pallidus administered as a neuroprotective measure to
      avoid lesioning of the internal capsule during stereotactic pallidotomy for
      treatment of Parkinson's disease. Left sided stimulation resulted in lower
      thresholds in right handed patients compared with left handed patients. These
      differences were significant in women, but no significant differences were found
      in men. In patients undergoing bilateral pallidotomy, the stimulation produced
      more significant left-right motor threshold differences. In the absence of known
      sex-related anatomical left-right corticospinal tract differences, the
      variability was the result of spinal excitability modulations most likely related
      to handedness.

PMID- 9285450
TI  - Constraints on the cerebral basis for semantic processing from neuroimaging
      studies of Alzheimer's disease.
AB  - OBJECTIVE: Functional activation studies of semantic processing in healthy adults
      have yielded conflicting results. The purpose was to evaluate the relative role
      of the brain regions implicated in semantic processing with converging evidence
      from imaging studies of patients with impaired semantic processing. METHODS:
      Semantic memory was assessed in patients with Alzheimer's disease using two
      measures, and these performance patterns were related to profiles of reduced
      cerebral functioning obtained with high resolution single photon emission
      computed tomography (SPECT). Patients with frontotemporal degeneration were
      similarly evaluated as a control group. RESULTS: Reduced relative cerebral
      perfusion was seen in parietal and posterior temporal brain regions of patients
      with Alzheimer's disease but not patients with frontotemporal degeneration.
      Impairments on semantically guided category membership decision tasks were also
      seen in patients with Alzheimer's disease but not those with frontotemporal
      degeneration. Performance on the semantic measures correlated with relative
      cerebral perfusion in inferior parietal and superior temporal regions of the left
      hemisphere only in Alzheimer's disease. Relative perfusion was significantly
      lower in these regions in patients with Alzheimer's disease with semantic
      difficulty compared with patients with Alzheimer's disease with relatively
      preserved semantic processing. CONCLUSION: These findings provide converging
      evidence to support the contribution of superior temporal and inferior parietal
      regions of the left hemisphere to semantic processing.

PMID- 9285452
TI  - Axonal neuropathy associated with monoclonal gammopathy of undetermined
      significance.
AB  - OBJECTIVE: The neuropathy associated with monoclonal gammopathy of undetermined
      significance (MGUS) is typically a predominantly demyelinating process that may
      have additional features of axonal degeneration. Sixteen patients with MGUS and a
      pure or predominantly axonal neuropathy are reported and compared with 20
      consecutive patients with demyelinating neuropathy and MGUS who were seen during
      the same period. METHODS: Retrospective review of a consecutive series of
      patients with neuropathy and MGUS evaluated during a five year period. RESULTS:
      The axonal group had mild, symmetric, slowly progressive, predominantly sensory
      neuropathy, usually limited to the legs. There were no differences in the age of
      onset or duration of symptoms at the time of presentation, initial symptoms, or
      the severity of weakness between the axonal and demyelinating cases. However, the
      axonal process was associated with less vibration and proprioceptive loss, did
      not include leg ataxia (present in 55% of patients with demyelinating type), less
      often had generalised areflexia (19% v 70%), IgM gammopathy (19% v 80%), and anti
      MAG antibodies (0% v 40%), and had lower CSF protein concentrations (mean, 49 v
      100 mg/dl). The illness was also generally milder with less disability (mean
      Rankin score 2.1 v 2.8). Fewer patients with axonal neuropathy improved with
      immunomodulating therapy (27% v 75%). CONCLUSION: There is an axonal neuropathy
      associated with MGUS that is clinically and electrophysiologically distinct from
      the more typical demyelinating pattern.

PMID- 9285453
TI  - Relation between psychiatric disorder and abnormal illness behaviour in patients
      undergoing operations for cervical discectomy.
AB  - OBJECTIVE: To test the hypothesis that depression in patients being considered
      for cervical disc surgery is associated with severe organic pathology. Secondly,
      to test whether depression and abnormal illness attitudes recorded preoperatively
      would predict poorer recovery. METHODS: Seventy four patients with pain and
      disability from cervical arthrosis were examined during investigations before
      potential cervical surgery. The prevalence of psychiatric disorder was assessed
      using the SCAN, and attitude to illness using the illness attitude scale.
      RESULTS: There was a rate of depressive disorder in the sample of 37%. The
      depressed patients did not have more severe organic pathology, more neurological
      symptoms or signs, or more disablement. They reported more pain and displayed
      more abnormal illness behaviour. Fifty patients went on to cervical surgery.
      Outcome four to eight months postoperatively was not related to the presence of
      psychiatric disorder or illness attitude recorded preoperatively. CONCLUSION:
      Depressive disorder is not secondary to severe pathology; the outcome of surgery
      is predominantly determined by physical factors.

PMID- 9285454
TI  - Wilson's disease.

PMID- 9285455
TI  - Needle EMG of the tongue: motor unit action potential versus peak ratio analysis
      in limb and bulbar onset amyotrophic lateral sclerosis.
AB  - OBJECTIVES: To find out if conventional and automatic needle EMG of the tongue
      can be helpful in the diagnosis and differentiation of limb and bulbar onset
      amyotrophic lateral sclerosis. METHODS: Motor unit action potential (MUAP)
      analysis and peak ratio interference pattern analysis were performed in the right
      genioglossus muscle of 30 healthy subjects aged 30-81 years, 10 patients aged 49
      73 years with limb onset amyotrophic lateral sclerosis, and eight patients aged
      52-75 years with bulbar onset amyotrophic lateral sclerosis. Electrical activity
      was sampled via standard concentric needle electrodes with a commercially
      available EMG recorder. RESULTS: Normal mean (2SD) MUAP duration was 6.6 (1.5)
      ms. Normal mean (2SD) MUAP amplitude was 224 (97.4) microV. Normal mean (2SD)
      peak ratio (PR), turns/second (T/s), amplitude/turn (A/T), and time intervals
      (TI1, TI2, TI3) were 1.68 (0.56), 732 (303.9), 446 (180.3) microV, 2.62 (0.34),
      2.31 (0.14), and 1.01 (0.50) respectively. Mean MUAP duration and amplitude were
      significantly increased in limb onset (P=0.0001 and P=0.013) and bulbar onset
      amyotrophic lateral sclerosis (P=0.0001 and P=0.017). Peak ratio indices stayed
      unchanged in limb onset amyotrophic lateral sclerosis but were significantly
      decreased (PR, T/s, A/T, TI1, and TI2) or increased (TI3) in bulbar onset
      disease. The sensitivity of the MUAP analysis was 70% in limb and 75% in bulbar
      onset amyotrophic lateral sclerosis. The sensitivity of the peak ratio
      interference pattern analysis was 20% in limb and 100% in bulbar onset
      amyotrophic lateral sclerosis. Subclinical involvement of the tongue was found in
      20% of the patients with limb onset amyotrophic lateral sclerosis and could be
      more accurately assessed with MUAP analysis than with automatic EMG. CONCLUSIONS:
      Both conventional and automatic needle EMG of the tongue are valuable
      electrophysiological devices to assess the clinical and subclinical involvement
      of the tongue in patients with limb and bulbar onset amyotrophic lateral
      sclerosis.

PMID- 9285456
TI  - Cortical and subcortical glucose metabolism in childhood epileptic
      encephalopathies.
AB  - OBJECTIVES: Nearly one third of children with cryptogenic epileptic
      encephalopathies have been reported to have focal cortical defects on
      18fluorodeoxyglucose (FDG) PET. As diffuse cortical dysfunction and involvement
      of subcortical structures, particularly the thalami, is postulated to underlie
      the propensity to seizures in these conditions, the aim was to determine the
      frequency of bilateral and diffuse cortical metabolic defects and of subcortical
      metabolic abnormalities in the same patients. METHODS: The interictal uptake of
      FDG was studied in 32 children with epileptic encephalopathies. Using a
      semiquantitative technique, the ratio of uptake in cortical regions and
      subcortical structures to that in the cerebellum was compared with that of age
      matched historical controls. Uptake more than 2 SD above ("hypermetabolic") or
      below ("hypometabolic") that of age matched controls was considered abnormal.
      RESULTS: Diffusely abnormal cortical up-take (nearly always hypometabolic)
      occurred in almost two thirds of patients; in all but two of the remaining
      patients at least one cortical region showed significantly decreased uptake
      bilaterally. When analysed as age cohorts, the mean cortical:cerebellar FDG
      uptake was significantly lower than that of controls in all cortical regions
      (P<0.005). Ninety per cent of patients had evidence of relative thalamic
      hypometabolism and in each age group there was a significant reduction in
      relative thalamic FDG uptake compared with that of controls (P<0.005). In nine
      out of 11 patients with unilateral cortical hypometabolic defects thalamic FDG up
      take was lower ipsilateral to the cortical abnormality. CONCLUSIONS: Diffuse
      cortical dysfunction is common in the epileptic encephalopathies and may reflect
      the underlying cause of the condition or arise as a consequence of uncontrolled
      seizures. Altered thalamic glucose metabolism is further evidence of subcortical
      involvement in these conditions.

PMID- 9285457
TI  - Functional asymmetries in the movement kinematics of patients with Tourette's
      syndrome.
AB  - OBJECTIVES: This study adopted a concurrent task design and aimed to quantify the
      efficiency and smoothness of voluntary movement in Tourette's syndrome via the
      use of a graphics tablet which permits analysis of movement profiles. In
      particular, the aim was to ascertain whether a concurrent task (digit span) would
      affect the kinematics of goal directed movements, and whether patients with
      Tourette's syndrome would exhibit abnormal functional asymmetries compared with
      their matched controls. METHODS: Twelve patients with Tourette's syndrome and
      their matched controls performed 12 vertical zig zag movements, with both left
      and right hands (with and without the concurrent task), to large or small targets
      over long or short extents. RESULTS: With short strokes, controls showed the
      predicted right hand superiority in movement time more strongly than patients
      with Tourette's syndrome, who instead showed greater hand symmetry with short
      strokes. The right hand of controls was less force efficient with long strokes
      and more force efficient with short strokes, whereas either hand of patients with
      Tourette's syndrome was equally force efficient, irrespective of stroke length,
      with an overall performance profile similar to but better than that of the
      controls' left hand. The concurrent task, however, increased the force efficiency
      of the right hand in patients with Tourette's syndrome and the left hand in
      controls. CONCLUSIONS: Patients with Tourette's syndrome, compared with controls,
      were not impaired in the performance of fast, goal directed movements such as
      aiming at targets; they performed in certain respects better than controls. The
      findings clearly add to the growing literature on anomalous lateralisation in
      Tourette's syndrome, which may be explained by the recently reported loss of
      normal basal ganglia asymmetries in that disorder.

PMID- 9285458
TI  - Late onset familial dystonia: could mitochondrial deficits induce a diffuse
      lesioning process of the whole basal ganglia system?
AB  - BACKGROUND: Striatal necrosis has been related to various clinical syndromes,
      with acute or chronic progression, and juvenile or late occurrence, but the most
      common type is Leigh's encephalopathy. METHODS: Between 1967 and 1995, six out of
      seven related patients with chronic familial dystonia were examined. MRIs were
      performed in four, between 1992-1994. The seven members, affected over three
      generations, were the father, three daughters (one surviving), and three
      surviving grandsons. RESULTS: The leading symptoms were gait disorders and
      dystonia in all, dysarthria in six, verbal and motor stereotypies in two, and
      parkinsonian and cerebellar signs in three. Optic neuropathy was found in three.
      A frontal lobe syndrome without amnesia occurred in two. Symptoms occurred
      between the second and the fifth decade, with progressive deterioration. Magnetic
      resonance imaging, performed in four, showed in the two patients with severe
      neurological signs diffuse striatopallidal abnormal hyposignal (comparable with
      CSF signal) in T1 weighted images, suggesting extensive necrosis of the striatum
      and pallidum, associated with thalamo-subthalamo-rubro-dentato-nigral and
      substantia innominata hypersignals in T2 weighted images suggesting gliosis in
      these respective areas. The same images were described to a lesser extent in a
      third patient. Concentrations of lactate in CSF and serum were normal in three.
      Muscle biopsy, performed in four, was shown to be normal. Enzyme histochemistry
      showed complex I, III, and IV deficiency in surviving patients. CONCLUSION: This
      familial dystonia of chronic progression may be related to basal ganglia necrosis
      or gliosis, associated with alterations in the respiratory chain. These metabolic
      alterations probably play a part in the pathophysiology of these unusual brain
      lesions.

PMID- 9285459
TI  - Effect of intrathecal baclofen delivered by an implanted programmable pump on
      health related quality of life in patients with severe spasticity.
AB  - OBJECTIVES: To compare clinical effectiveness and health related quality of life
      in patients with severe spasticity who received intrathecal baclofen or a
      placebo. METHODS: In a double blind, randomised, multicentre trial 22 patients
      were followed up during 13 weeks and subsequently included in a 52 week
      observational longitudinal study. Patients were those with chronic, disabling
      spasticity who did not respond to maximum doses of oral baclofen, dantrolene, and
      tizanidine. After implantation of a programmable pump patients were randomly
      assigned to placebo or baclofen infusion for 13 weeks. After 13 weeks all
      patients received baclofen. Clinical efficacy was assessed by the Ashworth scale,
      spasm score, and self reported pain, and health related quality of life by the
      sickness impact profile (SIP) and the Hopkins symptom checklist (HSCL). RESULTS:
      At three months the scores of the placebo and baclofen group differed slightly
      for the spasm score (effect size=0.20) and substantially for the Ashworth scale
      (effect size=1.40) and pain score (effect size=0.94); health related quality of
      life showed no significant differences. Three months after implantation the
      baclofen group showed a significant, substantial improvement on the SIP "physical
      health", "mental health", "mobility", and "sleep and rest" subscales and on the
      HSCL mental health scale; patients receiving placebo showed no change. After one
      year of baclofen treatment significant (P<0.05) improvement was found on the SIP
      dimensions "mobility" and "body care and movement" with moderate effect sizes.
      Improvement on the SIP subscale "physical health" (P<0.05; effect size 0.86), the
      SIP overall score (without "ambulation"), and the "physical health" and overall
      scale of the HSCL was also significant, with effect sizes >0.80. Changes in
      health related behaviour were noted for "sleep and rest" and "recreation and
      pastimes" (P<0.01, P<0.05; effect size 0.95 and 0.63, respectively). Psychosocial
      behaviour showed no improvement. CONCLUSIONS: Intrathecal baclofen delivered by
      an implanted, programmable pump resulted in improved self reported quality of
      life as assessed by the SIP, and HSCL physical health dimensions also suggest
      improvement.

PMID- 9285460
TI  - Involuntary movements during thermolesion predict a better outcome after
      microelectrode guided posteroventral pallidotomy.
AB  - Eight of the first 15 patients with advanced Parkinson's disease who underwent
      microelectrode guided posteroventral pallidotomy developed transient abnormal
      involuntary movements during thermolesion, four of whom also did so during high
      frequency macrostimulation. Abnormal involuntary movements found before
      thermolesion were choreic, ballistic, or choreoathetoid in nature, usually
      persisted less than 60 minutes, and were contralateral to the site of
      thermolesion in six and bilateral in two of them. The appearance of abnormal
      involuntary movements during macrostimulation or thermolesion of the internal
      globus pallidus correlated with better surgical outcome as measured by UPDRS
      motor items and CAPIT timed test, so that they seem to be of prognostic value.

PMID- 9285461
TI  - Medial temporal structures relate to memory impairment in Alzheimer's disease: an
      MRI volumetric study.
AB  - OBJECTIVES: Memory impairment is not only the earliest clinical symptom but a
      central and prominent feature throughout the course of Alzheimer's disease.
      Alzheimer related pathological alterations in the medial temporal structures may
      account for the memory impairments in patients with Alzheimer's disease. The aim
      of this study was to elucidate the role of the medial temporal structures in
      memory impairment caused by Alzheimer's disease. METHODS: Using high resolution
      MRI and a semiautomated image analysis technique, volumes of the medial temporal
      structures (amygdaloid complex, hippocampal formation, subiculum, and
      parahippocampal gyrus) were measured, and correlations between atrophy of each
      structure and memory dysfunction in patients with Alzheimer's disease were
      examined. RESULTS: Patients with Alzheimer's disease showed poor performance on
      verbal and non-verbal memory tests, and MRI volumetry showed a significant volume
      reduction of the medial temporal lobe structures. Volumes of the amygdaloid
      complex and of the subiculum correlated with memory performance. Stepwise
      regression analyses disclosed that the volume of the right amygdaloid complex
      specifically predicted visual memory function and to some extent verbal memory
      function, and that the volume of the left subiculum specifically predicted verbal
      memory function. Atrophy of the hippocampus did not predict severity of memory
      impairment. CONCLUSIONS: The presence of perihippocampal damage involving the
      amygdala proper, its surrounding cortex, and the subiculum further increased the
      severity of memory impairment attributable to hippocampal damage in Alzheimer's
      disease.

PMID- 9285462
TI  - Cognitive recovery instead of decline after acute encephalitis: a prospective
      follow up study.
AB  - OBJECTIVE: Follow up of cognitive sequelae of acute encephalitis and estimation
      of the frequency of persisting dementia. METHODS: Out of a series of 45
      consecutive patients with acute encephalitis prospectively studied in 1990-95, 40
      were screened for difficulty in everyday life using the Blessed dementia scale
      (BDS) 3.7 (1.4), mean (SD), years after onset. Eight patients had had herpes
      simplex encephalitis (HSVE), 16 some other identified aetiology, and in 21 the
      aetiology was unknown. All, except two patients with a nonherpetic encephalitis,
      were treated with acyclovir. All patients with disability in BDS (12/40), were
      invited to a neuropsychological reassessment, and the results of this assessment
      were compared with those of a similar assessment done after the acute stage. At
      follow up one patient could not complete the tests due to intractable epilepsy.
      RESULTS: In six of 11 cases the symptoms causing disability were mainly
      psychiatric. Five patients (two with HSVE) had a pronounced memory impairment
      together with other cognitive deficits, indicating dementia (frequency of 12.8%).
      In eight of the 11 testable cases cognitive performance had improved over the
      years, in two cases a decline was found and one patient with severe deficits
      showed no change. Intractable epilepsy was found in four of 12 cases. CONCLUSION:
      Cognitive decline had taken place already at the acute stage, and further
      deterioration was uncommon. Considerable improvement occurred in most patients
      during follow up. Also in patients with HSVE treated with acyclovir the cognitive
      recovery was substantial and of a magnitude not expected based on previous
      literature. Intractable epilepsy contributed to the cognitive deterioration in
      some cases. Affective disorders also had a surprisingly important role for the
      long term outcome.

PMID- 9285463
TI  - Autonomic effects of selegiline: possible cardiovascular toxicity in Parkinson's
      disease.
AB  - OBJECTIVES: The United Kingdom Parkinson's Disease Research Group (UKPDRG) trial
      found an increased mortality in patients with Parkinson's disease randomised to
      receive selegiline (10 mg/day) and levodopa compared with those taking levodopa
      alone. Unwanted effects of selegiline on cardiovascular regulation have been
      investigated as a potential cause for the unexpected mortality finding of the
      UKPDRG trial. METHODS: The cardiovascular responses to a range of physiological
      stimuli, including standing and head up tilt, were studied in patients with
      Parkinson's disease receiving levodopa alone and a matched group on levodopa and
      selegiline. RESULTS: Head up tilt caused selective and often severe orthostatic
      hypotension in nine of 16 patients taking selegiline and levodopa, but was
      without effect on nine patients receiving levodopa alone. Two patients taking
      selegiline lost consciousness with unrecordable blood pressures and a further
      four had severe symptomatic hypotension. The normal protective rises in heart
      rate and plasma noradrenaline were impaired. The abnormal response to head up
      tilt was reversed by discontinuation of selegiline. Drug withdrawal caused a
      pronounced deterioration in motor function in 13 of the 16 patients taking
      selegiline. CONCLUSION: Therapy with selegiline and levodopa in combination may
      be associated with severe orthostatic hypotension not attributable to levodopa
      alone. Selegiline also has pronounced symptomatic motor effects in advanced
      Parkinson's disease. The possibilities that these cardiovascular and motor
      findings might be due either to non-selective inhibition of monoamine oxidase or
      to amphetamine and met-amphetamine are discussed.

PMID- 9285465
TI  - Karl Friedrich Gauss (1777-1855).

PMID- 9285466
TI  - Neurofibrillary tangles in Gerstmann-Straussler-Scheinker syndrome with the A117V
      prion gene mutation.
AB  - One patient of a French family with Gerstmann-Straussler-Scheinker syndrome with
      the mutation in codon 117 of the prion protein (PrP) gene displayed unexpected
      neuritic degeneration around PrP plaques and numerous diffuse neurofibrillary
      tangles, whereas other members did not. The tau profile in this patient's brain
      was analysed and compared with one from another member of the Gerstmann
      Straussler-Scheinker family as well as with the Alzheimer's tau profile. A panel
      of well characterised antibodies against both normal tau protein and paired
      helical filaments-tau protein was used on immunoblots of brain proteins resolved
      by mono and two dimensional gels. The tau profile in the patient with Gerstmann
      Straussler-Scheinker syndrome without neurofibrillary tangles was normal. The tau
      profile from the patient with Gerstmann-Straussler-Scheinker syndrome and
      neurofibrillary tangles was characterised by a hyperaggregation state of tau
      protein. This case illustrates the phenotypic heterogeneity of the GSS117
      mutation not only from one family to another, but also between members of the
      same family. In this family, the presence of neurofibrillary tangles is still
      unexplained, but could be correlated with either the protracted duration of the
      disease or the old age of the patient.

PMID- 9285464
TI  - Perfusion patterns in postictal 99mTc-HMPAO SPECT after coregistration with MRI
      in patients with mesial temporal lobe epilepsy.
AB  - OBJECTIVES: To assess patterns of postictal cerebral blood flow in the mesial
      temporal lobe by coregistration of postictal 99mTc-HMPAO SPECT with MRI in
      patients with confirmed mesial temporal lobe epilepsy. METHODS: Ten postictal and
      interictal 99mTc-HMPAO SPECT scans were coregistered with MRI in 10 patients with
      confirmed mesial temporal lobe epilepsy. Volumetric tracings of the hippocampus
      and amygdala from the MRI were superimposed on the postictal and interictal
      SPECT. Asymmetries in hippocampal and amygdala SPECT signal were then calculated
      using the equation: % Asymmetry =100 x (right - left) / (right + left)/2.
      RESULTS: In the postictal studies, quantitative measurements of amygdala SPECT
      intensities were greatest on the side of seizure onset in all cases, with an
      average % asymmetry of 11.1, range 5.2-21.9. Hippocampal intensities were
      greatest on the side of seizure onset in six studies, with an average % asymmetry
      of 9.6, range 4.7-12.0. In four scans the hippocampal intensities were less on
      the side of seizure onset, with an average % asymmetry of 10.2, range 5.7-15.5.
      There was no localising quantitative pattern in interictal studies. CONCLUSIONS:
      Postictal SPECT shows distinctive perfusion patterns when coregistered with MRI,
      which assist in lateralisation of temporal lobe seizures. Hyperperfusion in the
      region of the amygdala is more consistently lateralising than hyperperfusion in
      the region of the hippocampus in postictal studies.

PMID- 9285467
TI  - Neuropsychology of thallium poisoning.
AB  - Cases of thallium poisoning are rare and neuropsychological assessment has only
      been reported in detail in one other case. In the case reported here,
      neuropsychological assessments were carried out three, 12, and 54 months after
      diagnosis of thallium poisoning in a man who had acutely shown a number of
      neurological signs including confusion and disorientation and generalised slowing
      of EEG which was more prominent on the left. Evidence suggested that he had been
      exposed to thallium over a period of weeks. Neuropsychological assessment
      indicated an unexpected weakness in verbal abilities which persisted. This
      finding is consistent with the only other published case report which details
      neuropsychological effects after a single large dose of thallium and which also
      found a lateralised impairment.

PMID- 9285468
TI  - Electrophysiological observations on an unusual, task specific jaw tremor.
AB  - A patient with no other neurological signs or symptoms presented with a prominent
      tremor restricted to the mandible. This 5-6 Hz tremor was interesting in that it
      was normally confined to the digastric muscles and was highly task specific. In
      the course of her normal daily activities, it began only when the patient drank
      from a cup or glass. The localisation of this tremor to a muscle that has no
      muscle spindles and no reciprocal inhibitory reflexes suggests that such tremors
      must be capable of being generated centrally.

PMID- 9285469
TI  - Tetraparesis after posterior fossa surgery.

PMID- 9285470
TI  - HIV related vasculitic mononeuropathy multiplex: a role for IVIg?

PMID- 9285471
TI  - Eyebrow lifting test: a novel bedside test for narrowing of the palpebral fissure
      associated with peripheral facial nerve palsy.

PMID- 9285472
TI  - Generalised motor neuron disease as an unusual manifestation of Borrelia
      burgdorferi infection.

PMID- 9285473
TI  - Severe but transient parkinsonism after tetanus vaccination.

PMID- 9285474
TI  - Cardiogenic syncope in temporal lobe epileptic seizures.

PMID- 9285475
TI  - Recurrent coital amnesia.

PMID- 9285477
TI  - Dostoevsky's epilepsy induced by television.

PMID- 9285476
TI  - Severe sensorimotor polyradiculoneuropathy after ingestion of ethylene glycol.

PMID- 9285478
TI  - Ecstatic seizures induced by television.

PMID- 9285479
TI  - Apolipoprotein E: non-cognitive symptoms and cognitive decline in late onset
      Alzheimer's disease.

PMID- 9285480
TI  - Negative regulation of cytokine gene transcription.
AB  - Cytokines are a class of soluble proteins that mediate signals throughout the
      immune system as well as between immune effector cells and other cell
      populations. This class of proteins includes interleukins, interferons, and
      chemokines. The expression of cytokines is tightly controlled in the producing
      cells, and one of the most important regulatory steps in this control is gene
      transcription. The transcription of most cytokine genes is silent until a
      producing cell is activated by extracellular stimuli. It is very common that
      transcription of these genes initiates immediately upon activation and shuts down
      quickly even in the continuous presence of the stimulating agent. Work performed
      over the past decade has revealed much about the molecular mechanism responsible
      for transcriptional regulation of these genes. Positive and negative
      transcription factors function in a concerted manner to regulate transcription of
      a specific cytokine at the promoter or intron region. We focus on recent progress
      in the field of transcriptional regulation of cytokine genes with an emphasis on
      the negative regulation of cytokine gene transcription.

PMID- 9285481
TI  - The Hill equation revisited: uses and misuses.
AB  - The Hill coefficient is commonly used to estimate the number of ligand molecules
      that are required to bind to a receptor to produce a functional effect. However,
      for a receptor with more than one ligand binding site, the Hill equation does not
      reflect a physically possible reaction scheme; only under the very specific
      condition of marked positive cooperativity does the Hill coefficient accurately
      estimate the number of binding sites. The Hill coefficient is best thought of as
      an "interaction" coefficient, reflecting the extent of cooperativity among
      multiple ligand binding sites. Several relatively simple, physically plausible
      reaction schemes are shown here to produce a variety of ligand dose-response
      curve phenotypes more appropriately suited to modeling ligand-receptor
      interactions, especially if independent information about the stochiometry of the
      ligand-receptor interaction is available.

PMID- 9285482
TI  - Calmodulin-dependent protein kinase II mediates signal transduction in apoptosis.
AB  - The present studies describe a new function for calmodulin-dependent protein
      kinase II (CaM-KII) in signal transduction leading to apoptosis. Both tumor
      necrosis factor alpha (TNF) and UV light rapidly stimulated Ca2+-independent
      activity of CaM-KII in the monocytic leukemia, U937. Two mechanistically
      different inhibitors of CaM-KII blocked activation of CaM-KII and prevented DNA
      fragmentation and death. Activation of CaM-KII during apoptosis and inhibition of
      DNA fragmentation by the two CaM-KII inhibitors were reproduced in several other
      lines including KGla, HL-60, and YAC-1. However, K562, which is relatively
      resistant to apoptosis induced by either TNF or UV light, did not activate CaM
      KII in response to these stimuli. A variant derived from U937 that is resistant
      to TNF- or UV light-induced apoptosis also lacked a CaM-KII response. Activation
      of Cam-KII was blocked by two protease inhibitors, VAD-fmk and TPCK, but not by
      other inhibitors of serine proteases. Both inhibitors of CaM-KII and the protease
      inhibitors blocked activation of AP24, a serine protease originally isolated from
      apoptotic cells that induces DNA fragmentation in nuclei. Our evidence supports a
      model in which proteolytic activity functions upstream of CaM-KII. This kinase
      then leads to activation of AP24, which transmits signals to the nucleus to
      initiate DNA fragmentation.

PMID- 9285484
TI  - Regulation of L-type calcium channels by protein tyrosine kinase and protein
      kinase C in cultured rat and human retinal pigment epithelial cells.
AB  - The effect of protein tyrosine kinases (PTKs) on L-type calcium channel currents
      was studied in cultured rat and human retinal pigment epithelial cells. Barium
      currents through L-type channels were measured in the perforated patch-clamp
      technique and identified by using the L-type calcium channel opener Bay K8644
      (10(-6) M). Application of the PTK blockers genistein (5 x 10(-6) M) or
      lavendustin A (5 x 10(-6) M) led to a decrease of L-type currents. The inactive
      genistein analog daidzein (10(-5) M) showed no effect on calcium channels.
      Intracellular application of pp60(c-src) (30 U/ml) via the patch-pipette during
      the conventional whole-cell configuration led to an increase of L-type currents.
      The protein kinase A and protein kinase G blocker H9 (10(-6) M) showed no effect
      on L-type currents; genistein reduced the current in the presence of H9. The
      protein kinase C (PKC) blocker chelerythrine (10(-5) M) reduced the L-type
      current; additional inhibition of PTK by lavendustin showed an additional
      reduction of currents. Intracellular application of myristoylated PKC substrate
      (5 x 10(-5) M) for PKC inhibition led to a fast rundown of L-type current
      amplitudes. Intracellularly applied myristoylated PKC substrate (10(-4) M)
      together with pp60(c-src) showed no effect on L-type current. Up-regulation of
      PKC by 10(-6) M phorbol-12-myristate-13-acetate (PMA) had no effect on the L-type
      current amplitude. However, genistein in cells pretreated with PMA led to an
      increase of the L-type currents. Intracellular application of pp60(c-src) in PMA
      treated cells led to a reduction of L-type currents. We conclude that in the
      resting cell, PTK and PKC regulate L-type calcium channels in an additive manner.
      L-type channels appeared as a site of integration of PTK activation and of PKC
      dependent pathways. The activity of PKC determines whether PTK decreases or
      increases L-type channel activity.

PMID- 9285483
TI  - The lipid peroxidation end product 4-hydroxy-2,3-nonenal up-regulates
      transforming growth factor beta1 expression in the macrophage lineage: a link
      between oxidative injury and fibrosclerosis.
AB  - An increasing number of reports underscore the frequent association of
      fibrosclerotic diseases of lung, liver, arterial wall, brain, etc., with the
      accumulation of oxidatively modified lipids and proteins. A cause-and-effect
      relationship has been proposed between cellular oxidative damage and increased
      fibrogenesis based on the fact that experimental treatment with antioxidants
      either prevents or quenches the fibrotic process. With some peculiarities in the
      different organs, fibrosclerosis is essentially the result of the interaction of
      macrophages and extracellular matrix-producing cells. The cross-talk is mediated
      by fibrogenic cytokines, among which the most important appears to be
      transforming growth factor beta1 (TGF-beta1). This report describes treatment of
      different types of macrophage, of both human and murine origin, with 4-hydroxy
      2,3-nonenal (HNE) a major aldehyde end product of membrane lipid oxidation found
      consistently to induce both mRNA expression and synthesis of TGF-beta1. Since
      increased HNE levels have been demostrated in the cirrhotic liver and in the
      oxidatively modified low-density human lipoproteins associated with
      atherosclerosis, the up-regulation of macrophage TGF-beta1 by HNE appears to be
      involved in the pathogenesis of these and similar diseases characterized by
      fibrosclerosis.

PMID- 9285485
TI  - Endopeptidase 24.11 (CD10/NEP) is required for phorbol ester-induced growth
      arrest in Jurkat T cells.
AB  - Jurkat T cells express a functional endopeptidase 24.11 that is involved in the
      regulation of T cell activation. We have analyzed the effect of ectopic CD10
      expression in mutant Jurkat cell clones that fail to express CD10 and, unlike
      wild-type cells, are resistant to the growth-inhibitory effects of the protein
      kinase C activator, PMA. No differences in the expression of the mRNA encoding
      the alpha, beta, gamma, delta, epsilon, and zeta isoforms of PKC were found in
      parental vs. PMA-resistant Jurkat cells, ruling out the possibility that the
      defect could be accounted for by an altered expression of one of these isoforms.
      Phorbol ester-induced growth arrest was not due to apoptosis since PMA failed to
      trigger DNA fragmentation in parental and mutant Jurkat T cells. CD10 mRNA
      expression and activity were abrogated in four independent PMA-resistant Jurkat T
      cell clones compared to parental cells, whereas the activities of several other
      peptidases were unaffected. Transfection of one mutant clone with a functional
      endopeptidase 24.11 restored in a significant manner PMA-induced growth arrest in
      all the clones selected and tested, whereas transfection of an inactive form of
      endopeptidase 24.11 had no effect, demonstrating that the enzymatic activity of
      CD10 is critical in the mediation of the PMA growth arrest. The data presented
      here demonstrate that a functional CD10 is required for PMA-induced growth arrest
      in Jurkat cells and provide further evidence for a role of endopeptidase 24.11 in
      the regulation of tumor cell proliferation.

PMID- 9285486
TI  - [Ca2+] microdomains control agonist-induced Ca2+ release in intact HeLa cells.
AB  - We have monitored specifically the [Ca2+] in the lumen of the endoplasmic
      reticulum (ER) of intact HeLa cells using an ER-targeted low-Ca2+-affinity
      aequorin. The steady-state [Ca2+] in the ER was around 600 microM. Histamine
      induced a concentration-dependent decrease in lumenal [Ca2+], whose rate
      increased near one order of magnitude and became "quantal" when cytosolic [Ca2+]
      ([Ca2+]c) was clamped with the Ca2+ chelator BAPTA. This effect was not due to
      decreased Ca2+ pumping because simultaneous addition of a SERCA inhibitor
      produced only additive effects. Given that inhibition by [Ca2+]c of the inositol
      1,4,5-trisphosphate-gated channels requires a [Ca2+]c much higher than that
      observed in the bulk cytosol after histamine addition, we conclude that local
      [Ca2+]c microdomains at the site of release strongly inhibit agonist-induced Ca2+
      mobilization in intact cells. This effect should play a key role in the mechanism
      controlling cytosolic [Ca2+] oscillations and waves, and therefore in the
      generation of spatio-temporal Ca2+ patterns.

PMID- 9285487
TI  - Cyclooxygenase-2: an essential regulator of NO-mediated apoptosis.
AB  - Lipopolysaccharide/interferon gamma up-regulated inducible nitric oxide synthase
      and caused nitric oxide generation and concomitant apoptotic cell death in RAW
      264.7 macrophages. Exogenously supplied nitric oxide donors such as S
      nitrosoglutathione produced equivalent alterations. Preactivation of macrophages
      with a combination of lipopolysaccharide/interferon gamma under conditions of
      blocked NO synthase--N(G)-monomethyl-L-arginine addition--or stimulation with a
      low, nondestructive dose of S-nitrosoglutathione conferred protection against
      high and thus apoptotic NO concentrations. Here we report that induction of
      cyclooxygenase-2 during the preactivation period is a critical regulator of
      macrophage apoptosis. Under resting conditions, macrophages do not express
      cyclooxygenase-2, whereas lipopolysaccharide/interferon gamma/N(G)-monomethyl-L
      arginine prestimulation for 12-15 h caused protein expression. In parallel,
      preactivation of RAW cells with a low, nontoxic dose of S-nitrosoglutathione
      promoted protection and cyclooxygenase-2 up-regulation. To prove cyclooxygenase-2
      involvement during protection, we stably transfected RAW 264.7 macrophages with a
      rat cyclooxygenase-2 expression vector. Cyclooxygenase-2 overexpressing
      macrophages, preactivated with the calcium liberating and thus phopholipase A2
      activating agent A23187, revealed protection against exogenously supplied NO.
      Protection afforded by lipopolysaccharide/interferon gamma/N(G)-monomethyl-L
      arginine prestimulation was completely reversed by the addition of the
      cyclooxygenase-2 selective inhibitor NS-398 or in macrophages stably transfected
      with an antisense cyclooxygenase-2 expression vector. Our results point to
      cyclooxygenase-2 induction by lipopolysaccharide/interferon gamma/N(G)-monomethyl
      L-arginine or low-dose nitric oxide pretreatment conferring macrophage protection
      to the apoptotic action of nitric oxide.

PMID- 9285488
TI  - Target length and primer concentration affect the gain of c-erbB2 and p53
      amplicons.
AB  - Although quantitative polymerase chain reaction (PCR) using internal standards
      may perform reproducibly, the calibration of the normal level is problematic.
      Three test sequences (171, 213, and 260 base pairs [bp]) from the c-erbB2
      oncogene were separately coamplified with a 133 bp control sequence from the
      single copy gene p53 in differential PCR. Sequence length differences between the
      oncogene and control sequences influenced the ratio estimates, obviously because
      of less efficient synthesis of the longer sequence. Increase in primer
      concentration of the longer oncogene sequences adjusted this imbalance, and the
      expected ratio of 1.0 could be reached. The primer or target sequence also
      influenced the ratio estimate, since the 171 bp oncogene sequence was as
      efficiently synthesized as the 133 bp control sequence but with lower primer
      concentration. The 260 bp oncogene sequence produced the most stable results,
      probably because of clear band separation in polyacrylamide gel electrophoresis.
      A ratio estimate of 1.0 was produced by oncogene and control gene primer
      concentrations of 3.5 pmol/microl and 0.6 pmol/microl, respectively. Calibrated
      quantitative PCR methodology is applicable to many areas and offers an excellent
      tool for screening allele deletions, supernumerary alleles, or chromosomes
      associated with familial diseases or disease syndromes.

PMID- 9285489
TI  - From totipotent embryonic stem cells to spontaneously contracting smooth muscle
      cells: a retinoic acid and db-cAMP in vitro differentiation model.
AB  - Vascular smooth muscle cell (VSMC) differentiation is important in understanding
      vascular disease; however, no in vitro model is available. Totipotent mouse
      embryonic stem (ES) cells were used to establish such a model. To test whether
      the ES cell-derived smooth muscle cells expressed VSMC-specific properties, the
      differentiated cells were characterized by 1) morphological analysis, 2) gene
      expression, 3) immunostaining for VSMC-specific proteins, 4) expression of
      characteristic VSMC ion channels, and 5) formation of [Ca2+]i transients in
      response to VSMC-specific agonists. Treatment of embryonic stem cell-derived
      embryoid bodies with retinoic acid and dibutyryl-cyclic adenosine monophosphate
      (db-cAMP) induced differentiation of spontaneously contracting cell clusters in
      67% of embryoid bodies compared with 10% of untreated controls. The highest
      differentiation rate was observed when retinoic acid and db-cAMP were applied to
      the embryoid bodies between days 7 and 11 in combination with frequent changes of
      culture medium. Other protocols with retinoic acid and db-cAMP, as well as single
      or combined treatment with VEGF, ECGF, bFGF, aFGF, fibronectin, matrigel, or
      hypoxia did not influence the differentiation rate. Single-cell RT-PCR and
      sequencing of the PCR products identified myosin heavy chain (MHC) splice
      variants distinguishing between gut and VSMC isoforms. RT-PCR with VSMC-specific
      MHC primers and immunostaining confirmed the presence of VSMC transcripts and MHC
      protein. Furthermore, VSMC expressing MHC had typical ion channels and responded
      to specific agonists with an increased [Ca2+]i. Here we present a retinoic acid +
      db-cAMP-inducible embryonic stem cell model of in vitro vasculogenesis. ES cell
      derived cells expressing VSMC-specific MHC and functional VSMC properties may be
      a suitable system to study mechanisms of VSMC differentiation.

PMID- 9285490
TI  - S. cerevisiae and sulfur: a unique way to deal with the environment.
AB  - Saccharomyces cerevisiae is by far the best-studied unicellular eukaryote.
      Although yeast cells are very similar to higher eukaryotes in many respects,
      there is striking evidence that S. cerevisiae is not a perfect model for a
      eukaryotic cell (cf. 1). Here we report that yeast proteins contain a
      significantly lower amount of cysteine residues compared to other eukaryotes.
      Explanations for this phenomenon could not be found in the sulfur metabolism of
      yeast, which showed no major differences from other organisms (2-4). However,
      previous examinations could link a defect in sulfate uptake of S. cerevisiae to
      an increased resistance against toxic substances like selenate and chromate in
      the environment, which share the same permeases (5-7). This environmental problem
      might have caused S. cerevisiae to down-regulate its sulfate uptake and therefore
      lead to a lower amount of available sulfur in the cell, making it necessary to
      replace all dispensable sulfur amino acids in proteins. We show in two examples
      that S. cerevisiae proteins contain only such cysteine residues that are
      structurally or functionally needed. Therefore, we conclude that S. cerevisiae
      has solved a widespread environmental problem in a specific way which might be
      unique among eukaryotes.

PMID- 9285491
TI  - Approaches to improve epidemiological studies of diabetic neuropathy: insights
      from the Rochester Diabetic Neuropathy Study.
AB  - The quality of the epidemiological data on diabetic neuropathies remains poor for
      a variety of reasons. They include variability in 1) ascertainment of diabetes,
      2) the clinical varieties of diabetic patients studied, 3) characterization of
      neurological dysfunction, 4) abnormal limits for neurological examinations and
      tests, 5) minimal criteria for neuropathy, 6) correct attribution of nondiabetic
      neurological disease, 7) correct attribution of type of neuropathy, 8) estimating
      neuropathy from use of multiple tests, and 9) estimating severity of
      polyneuropathy. We have tried to remedy these short-comings in the Rochester
      Diabetic Neuropathy Study (RDNS). It was not possible to adequately characterize
      and quantitate diabetic polyneuropathies using only one or two clinical or test
      abnormalities. To estimate severity of diabetic polyneuropathy, the results of
      the neurological examination and abnormalities of nerve conduction, quantitative
      sensory tests, and quantitative autonomic tests were combined into a composite
      score. One begins by scoring a standard test of neurological deficits
      (impairments) of the lower limbs (NIS[LL]) and adds to this transformed numbers
      for percentile abnormality of seven good functional tests. This NIS(LL)+7 tests
      score appears to provide a much more comprehensive and stable numeric score by
      which to diagnose and grade severity of diabetic polyneuropathy than does the use
      of individual clinical or test results. This test score should be useful as a
      measure of change in diabetic polyneuropathy for purposes of medical practice,
      epidemiology studies, and controlled clinical trials. The staging approach that
      we introduced previously continues to provide an important measure of overall
      severity of diabetic polyneuropathy, taking into account both symptoms and
      impairments.

PMID- 9285492
TI  - Endothelial dysfunction: cause of the insulin resistance syndrome.
AB  - Insulin resistance has been proposed as the metabolic basis of atherogenesis.
      This hypothesis is based on the concept of the "insulin resistance syndrome,"
      according to which insulin resistance is viewed as the primary abnormality that
      gives rise to dyslipidemia, essential hypertension, impaired glucose tolerance,
      and NIDDM. However, this hypothesis takes no account of the well-established and
      central role of vascular endothelium in the atherogenic process. Although
      endothelial injury is an early and prominent feature of atherogenesis, relatively
      little attention has been given to its metabolic consequences. In subjects with
      NIDDM, we have shown that endothelial dysfunction is associated with insulin
      resistance, raising the question of whether this relationship could be causal. In
      this article, we review the factors that are considered to be responsible for the
      development of endothelial dysfunction during atherogenesis, together with the
      metabolic consequences of endothelial dysfunction. While dysfunction of the
      endothelium in large and medium-sized arteries plays a central role in
      atherogenesis, we argue that dysfunction of peripheral vascular endothelium, at
      arteriolar and capillary level, plays the primary role in the pathogenesis of
      both insulin resistance and the associated features of the insulin resistance
      syndrome. We propose that the insulin resistance syndrome, together with many
      aspects of atherogenesis, can be viewed as the diverse consequences of
      endothelial dysfunction in different vascular beds. This new and testable
      hypothesis accounts for both the endothelial and metabolic abnormalities
      associated with atherogenesis.

PMID- 9285493
TI  - Antioxidant defense: vitamins E and C and carotenoids.
AB  - Reactive oxygen species are thought to be implicated in the pathogenesis of
      various human diseases. They are generated endogenously under physiological and
      pathological conditions but also upon exposure to exogenous challenge. The
      organism maintains defense systems against reactive oxygen species, including
      enzymes and low-molecular-weight antioxidants. Important antioxidants such as
      vitamins E and C and carotenoids are provided from the diet. Vitamin E, as the
      major chain-breaking antioxidant, inhibits lipid peroxidation, thus preventing
      membrane damage and modification of low-density lipoproteins. It is regenerated
      by the water-soluble vitamin C. Carotenoids efficiently scavenge singlet
      molecular oxygen and peroxyl radicals. There is increasing evidence from
      epidemiological studies, animal experiments, and in vitro investigations that an
      increased intake of antioxidants is associated with a diminished risk for several
      diseases.

PMID- 9285494
TI  - Recent progress in advanced glycation end products and diabetic complications.

PMID- 9285495
TI  - Growth factor alterations in advanced diabetic retinopathy: a possible role of
      blood retina barrier breakdown.
AB  - Chronic hyperglycemia may cause growth factor alterations that are likely to
      participate in tissue remodeling typical for diabetic late complications.
      However, few details of such events are known. The ocular vitreous fluid allows
      studies of growth factor levels in human eyes (after vitrectomy). The vitreous is
      highly inert and protected by the blood-retina barrier and thus probably reflects
      growth factor production by the normal retina. Vitreous from patients with
      proliferative diabetic retinopathy (PDR) was compared with vitreous obtained from
      patients with nonproliferative eye disease and with vitreous from patients
      without diabetes but with marked neovascular proliferations due to ischemia. This
      design permits us to distinguish diabetes-related from non-diabetes-related
      alterations. Insulin-like growth factor I (IGF-I), IGF-II, IGF binding protein 2
      (IGFBP-2), and IGFBP-3 were elevated 3- to 13-fold in nondiabetic retinal
      ischemia and 1.5- to 3-fold in PDR, indicating that the changes were not
      restricted to diabetes. These changes may partially be explained by leakage of
      serum into the vitreous, since IGFs and IGFBPs are 20- to 50-fold higher in serum
      than in vitreous, and vitreous protein content was 1.5-fold elevated in PDR
      subjects and 5-fold in ischemia patients compared with control subjects. TGF-beta
      is a proposed antiangiogenic factor in the eye. TGF-beta2 was the predominant
      subtype in vitreous, and its total amount was not altered in PDR patients. More
      importantly, the active fraction of TGF-beta was decreased by 30 and 70% in PDR
      and nondiabetic retinal ischemia patients, respectively. Since plasmin may
      control TGF-beta activation, the serum protein alpha2-antiplasmin was measured
      and found to be significantly elevated to 150 and 250% of control values in PDR
      and ischemia patients, respectively. Thus, influx of serum proteins due to
      microvascular disturbances and hypoxia is proposed as a possible cause for
      vitreous alterations of IGF-I and of active TGF-beta. These changes seem to occur
      late in the sequence of events leading to PDR and are not specific for diabetes,
      but they were also observed in other diseases characterized by retinal hypoxia.

PMID- 9285496
TI  - Metabolic and vascular factors in the pathogenesis of diabetic neuropathy.
AB  - Reduced nerve perfusion is an important factor in the etiology of diabetic
      neuropathy. Studies in streptozotocin-induced diabetic rats show that nerve
      conduction velocity (NCV) and blood flow deficits are corrected by treatment with
      vasodilator drugs, with angiotensin II and endothelin-1 antagonists being
      particularly important. The AT1 antagonist ZD7155 also prevents diabetic deficits
      in regeneration following nerve damage, indicating that hypoperfusion is an
      important limitation for nerve repair. Metabolic changes include high polyol
      pathway flux, increased advanced glycosylation, elevated oxidative stress, and
      impaired omega-6 essential fatty acid metabolism. Aldose reductase inhibitors
      (ARIs) restore NCV via their effects on perfusion. ARI action probably depends on
      blocking the conversion of glucose to sorbitol, thus preventing depletion of vasa
      nervorum glutathione, an important endogenous free radical scavenger. Free
      radicals cause vascular endothelium damage and reduced nitric oxide vasodilation.
      Inhibition of advanced glycosylation and autoxidation (autoxidative
      glycosylation), major sources of free radicals, by aminoguanidine or transition
      metal chelators, corrects neurovascular dysfunction. Evening primrose oil
      supplies gamma-linolenic acid (GLA) to improve vasodilator eicosanoid synthesis
      in diabetes, correcting nerve blood flow and NCV deficits. Interactions between
      some of these mechanisms have therapeutic implications. Thus, combined ARI and
      evening primrose oil treatment produced a 10-fold amplification of NCV and blood
      flow responses. Similarly, GLA effects are markedly enhanced when given in
      combination with ascorbate as ascorbyl-GLA. Thus, metabolic abnormalities combine
      to produce deleterious changes in nerve perfusion that make a major contribution
      to the etiology of diabetic neuropathy. The potential importance of multi-action
      therapy is stressed.

PMID- 9285497
TI  - The roles of oxidative stress and antioxidant treatment in experimental diabetic
      neuropathy.
AB  - Oxidative stress is present in the diabetic state. Our work has focused on its
      presence in peripheral nerves. Antioxidant enzymes are reduced in peripheral
      nerves and are further reduced in diabetic nerves. That lipid peroxidation will
      cause neuropathy is supported by evidence of the development of neuropathy de
      novo when normal nerves are rendered alpha-tocopherol deficient and by the
      augmentation of the conduction deficit in diabetic nerves subjected to this
      insult. Oxidative stress appears to be primarily due to the processes of nerve
      ischemia and hyperglycemia auto-oxidation. The indexes of oxidative stress
      include an increase in nerve, dorsal root, and sympathetic ganglia lipid
      hydroperoxides and conjugated dienes. The most reliable and sensitive index,
      however, is a reduction in reduced glutathione. Experimental diabetic neuropathy
      results in myelinopathy of dorsal roots and a vacuolar neuropathy of dorsal root
      ganglion. The vacuoles are mitochondrial; we posit that lipid peroxidation causes
      mitochondrial DNA mutations that increase reduced oxygen species, causing further
      damage to mitochondrial respiratory chain and function and resulting in a sensory
      neuropathy. Alpha-lipoic acid is a potent antioxidant that prevents lipid
      peroxidation in vitro and in vivo. We evaluated the efficacy of the drug in doses
      of 20, 50, and 100 mg/kg administered intraperitoneally in preventing the
      biochemical, electrophysiological, and nerve blood flow deficits in the
      peripheral nerves of experimental diabetic neuropathy. Alpha-lipoic acid dose-
      and time-dependently prevented the deficits in nerve conduction and nerve blood
      flow and biochemical abnormalities (reductions in reduced glutathione and lipid
      peroxidation). The nerve blood flow deficit was 50% (P < 0.001). Supplementation
      dose-dependently prevented the deficit; at the highest concentration, nerve blood
      flow was not different from that of control nerves. Digital nerve conduction
      underwent a dose-dependent improvement at 1 month (P < 0.05). By 3 months, all
      treated groups had lost their deficit. The antioxidant drug is potentially
      efficacious for human diabetic sensory neuropathy.

PMID- 9285499
TI  - The pathology of human diabetic neuropathy.
AB  - Quantitative morphological data are presented from a series of studies assessing
      both nerve fiber and capillary pathology in 30 diabetic patients with varying
      stages and symptoms of neuropathy. There is a significant relationship between
      clinical measures of neuropathic severity and myelinated fiber loss. However,
      unmyelinated fibers continue to regenerate even in patients with established
      neuropathy. Microvascular abnormalities, particularly basement membrane
      thickening and endothelial cell hyperplasia, are an early feature of diabetic
      microangiopathy and relate to neuropathic severity. There are no
      neurophysiological or morphological differences between patients with type 1 and
      type 2 diabetes nor between diabetic patients with and without painful
      neuropathy.

PMID- 9285500
TI  - Classification, differential diagnosis, and staging of diabetic peripheral
      neuropathy.
AB  - The peripheral nerve disorders associated with diabetes are complex and probably
      involve a variety of causative mechanisms. This may give rise to difficulty in
      the classification of individual cases. A broad separation into rapidly
      reversible or more persistent phenomena is helpful. The former, which can be
      categorized as "hyperglycemic neuropathy," include minor sensory symptoms,
      reduced nerve conduction velocity, and resistance to ischemic conduction failure.
      From analogy with experimental studies in animals, nerve hypoxia is likely to
      play a significant role in their origin. Of the more persistent phenomena, a
      distal symmetric polyneuropathy that predominantly affects sensory and autonomic
      function is the most common manifestation. A distal axonopathy of dying-back type
      may represent the underlying pathogenetic basis. Other more persistent phenomena
      consist of focal and multifocal lesions giving rise to cranial, thoraco
      abdominal, and limb neuropathies, including proximal lower limb motor neuropathy
      (diabetic amyotrophy). Some of these may have an ischemic basis. Multifocal
      proximal lesions can summate to produce an approximately symmetric diffuse distal
      neuropathy. Focal lesions at sites of entrapment or external compression may
      reflect an abnormal susceptibility of diabetic nerve to compressive damage. There
      is also evidence that focal inflammatory, including vasculitic, lesions may be
      involved in proximal lower limb neuropathies. Finally, superimposed chronic
      inflammatory demyelinating polyneuropathy may occur. For the evaluation of
      possible treatment regimens, it is essential that cases should be correctly
      classified as to type. Thus, the features falling into the category of
      hyperglycemic neuropathy should not contaminate the assessment of distal
      symmetric polyneuropathy. For this type, a widely accepted scheme for staging
      devised by P. J. Dyck is available. Other schemes are also available for the
      assessment of such cases, with differing degrees of complexity. Evaluation by
      serial nerve biopsies has also been proposed.

PMID- 9285498
TI  - Role of neurotrophins in diabetic neuropathy and treatment with nerve growth
      factors.
AB  - In rodent models of diabetes, there are expression deficits in nerve growth
      factor (NGF) and in mRNA for its high-affinity receptor, trkA, leading to
      decreased retrograde axonal transport of NGF and decreased support of NGF
      dependent sensory neurons, with reduced expression of their neuropeptides,
      substance P and calcitonin gene-related peptide (CGRP). Treatment of diabetic
      rats with intensive insulin normalized these deficits, and treatment with
      exogenous NGF caused dose-related increases, giving levels of NGF and
      neuropeptides that were greater than those of controls. Neurotrophin-3 (NT-3)
      mRNA was also deficient in leg muscle from diabetic rats, and administration of
      recombinant NT-3 to diabetic rats increased the conduction velocity of sensory
      nerves without affecting motor conduction velocity. In regenerating nerves after
      experimental crush injury, expression of NGF in the nerve trunk is increased in
      diabetes to a greater extent than in controls, but this is offset by a greater
      reduction in the neuronal expression of trkA in dorsal root ganglia of diabetic
      rats. Nonetheless, targeted administration of exogenous NGF via impregnated
      conduits stimulated regeneration in both control and diabetic rats. These
      findings implicate deficient neurotrophic support in diabetic neuropathy and
      suggest that its correction should be a paramount therapeutic target.

PMID- 9285501
TI  - The pathogenesis of diabetic foot problems: an overview.
AB  - Foot ulceration and lower limb amputation are still common complications of
      diabetes. Diabetic peripheral neuropathy and peripheral vascular disease are the
      most important etiologic factors, but there is a complex interplay between these
      abnormalities and a number of other contributory factors, such as altered foot
      pressures, limited joint mobility, glycemic control, ethnic background, and
      cardiovascular parameters. Identification of patients at high risk of ulceration
      is nevertheless simple, and education of such patients can achieve a major
      reduction in amputation and ulceration rates.

PMID- 9285502
TI  - Alpha-lipoic acid in the treatment of diabetic peripheral and cardiac autonomic
      neuropathy.
AB  - Antioxidant treatment has been shown to prevent nerve dysfunction in experimental
      diabetes, providing a rationale for a potential therapeutic value in diabetic
      patients. The effects of the antioxidant alpha-lipoic acid (thioctic acid) were
      studied in two multicenter, randomized, double-blind placebo-controlled trials.
      In the Alpha-Lipoic Acid in Diabetic Neuropathy Study, 328 patients with NIDDM
      and symptomatic peripheral neuropathy were randomly assigned to treatment with
      intravenous infusion of alpha-lipoic acid using three doses (ALA 1,200 mg; 600
      mg; 100 mg) or placebo (PLAC) over 3 weeks. The total symptom score (TSS) (pain,
      burning, paresthesia, and numbness) in the feet decreased significantly from
      baseline to day 19 in ALA 1,200 and ALA 600 vs. PLAC. Each of the four individual
      symptom scores was significantly lower in ALA 600 than in PLAC after 19 days (all
      P < 0.05). The total scale of the Hamburg Pain Adjective List (HPAL) was
      significantly reduced in ALA 1,200 and ALA 600 compared with PLAC after 19 days
      (both P < 0.05). In the Deutsche Kardiale Autonome Neuropathie Studie, patients
      with NIDDM and cardiac autonomic neuropathy diagnosed by reduced heart rate
      variability were randomly assigned to treatment with a daily oral dose of 800 mg
      alpha-lipoic acid (ALA) (n = 39) or placebo (n = 34) for 4 months. Two out of
      four parameters of heart rate variability at rest were significantly improved in
      ALA compared with placebo. A trend toward a favorable effect of ALA was noted for
      the remaining two indexes. In both studies, no significant adverse events were
      observed. In conclusion, intravenous treatment with alpha-lipoic acid (600
      mg/day) over 3 weeks is safe and effective in reducing symptoms of diabetic
      peripheral neuropathy, and oral treatment with 800 mg/day for 4 months may
      improve cardiac autonomic dysfunction in NIDDM.

PMID- 9285503
TI  - Diagnosis of cardiovascular autonomic neuropathy in diabetes.
AB  - The utility of standard cardiovascular tests for diagnosis of cardiac autonomic
      neuropathy in diabetes has been well documented. Attention must be paid to
      standardizing the procedure with regard to time of day, metabolic status,
      distance from meal and insulin, coffee and smoking avoidance, and patient's
      collaboration. In the presence of cardiovascular disease or drugs affecting the
      cardiovascular or autonomic nervous system, some caution is needed in
      interpreting the results. More recent reflex tests, which evaluate mainly
      sympathetic or baroreflex activity, despite their ability to detect early
      autonomic involvement, lack sufficient standardization and still need to be
      proved as valid alternatives. Of the different methods of measuring heart rate
      variability, spectral analysis has a greater ability to differentiate vagal and
      sympathetic modulation of heart rate than do time-domain methods. However, since
      these latter methods are easier and more widely available, they can be used as a
      screening approach. Twenty-four-hour evaluation of heart rate variability
      provides data on the circadian rhythm of sympathovagal activity, which can be
      affected earlier than and differently from cardiovascular reflex tests.
      Information obtained could have prognostic implications in terms of
      cardiovascular morbidity and mortality and offer therapeutic opportunities.
      However, a wide consensus on many technical aspects of both time-domain and
      frequency-domain methods is needed. Furthermore, large prospective studies in the
      diabetic population to assess the prognostic value of 24-h heart rate variability
      parameters on cardiovascular morbidity and mortality are lacking. Recently, I123
      meta-iodobenzylguanidine (MIBG) scintigraphy has documented abnormalities of
      sympathetic myocardial innervation also in newly diagnosed IDDM. The meaning of
      this finding, whether it is an expression of functional or structural defects,
      needs to be clarified. Preliminary data point to a possible pathogenetic meaning
      of the known association between autonomic neuropathy and other diabetic
      complications. This area of investigation could provide useful insights into the
      complex and multifactorial pathogenesis of diabetic complications.

PMID- 9285504
TI  - Pathophysiology of diabetic gastroparesis.
AB  - Our understanding of the nature of diabetic gastroparesis has advanced in the
      last decade due to new investigational procedures (electrogastrography, visceral
      evoked potential recording), and transferring these insights into clinical
      routine will be our task in the future. Meanwhile, the clinical relevance of
      gastroparesis--whether overt or silent--remains unquestioned: proper gastric
      emptying is a prerequisite for adequate metabolic control, and its disturbance
      may result not only in further progression of the chronic complications of the
      disease, but also in the false assumption that these patients are not compliant
      with their doctor's management--the patients just may have delayed emptying of
      their stomach without noticing it.

PMID- 9285505
TI  - Aldose reductase inhibitors: the end of an era or the need for different trial
      designs?
AB  - Despite numerous attempts over 16 years, the results of aldose reductase
      inhibitor (ARI) trials for the treatment of diabetic neuropathy have not proven
      efficacy. This paper reviews each of the ARI trials, examines confounding
      factors, and proposes a future course. The confounding factors considered are
      pharmacokinetics (ARI penetration of human nerve), length of trial (in terms of
      the natural history of diabetic neuropathy), trial endpoints (reversibility or
      slowing of progression), reproducibility of clinical measurements (in terms of
      power calculations), standardization and quality control of endpoints, and
      clinically meaningful differences in endpoints. We conclude that ARIs are most
      likely to have a beneficial effect in the management of diabetic distal
      symmetrical polyneuropathy and autonomic neuropathy but that the clinical role of
      ARIs is to slow the progression of diabetic neuropathy rather than to reverse it.
      Future trials should be designed with adequate statistical power, with
      consideration of the variability of the endpoint measurements for long enough
      duration, and with rigorous quality control to definitively confirm the utility
      of ARIs in the treatment of diabetic distal symmetrical polyneuropathy and
      autonomic neuropathy.

PMID- 9285506
TI  - Essential fatty acids in the management of impaired nerve function in diabetes.
AB  - Impaired conversion of linoleic acid to gamma-linolenic acid (GLA) has been
      demonstrated in animal diabetes and inferred from blood fatty acid profiles in
      human diabetes. This impairment could theoretically lead to defective nerve
      function because metabolites of GLA are known to be important in nerve membrane
      structure, nerve blood flow, and nerve conduction. Administration of GLA corrects
      the impaired nerve function in animal models of diabetes. Two multicenter,
      randomized, placebo-controlled trials in humans with diabetic neuropathy have
      shown significant benefits of GLA as compared with placebo in neurophysiological
      parameters, thermal thresholds, and clinical sensory evaluations. Further work is
      needed to define the place of this therapeutic approach and its interactions with
      other treatment modalities.

PMID- 9285507
TI  - Upright posture and the microvasculature in human diabetic neuropathy: a
      hypothesis.

PMID- 9285508
TI  - Pathogenesis of diabetic vascular disease: evidence for the role of reduced
      heparan sulfate proteoglycan.
AB  - Insulin-dependent diabetic patients with increased urinary albumin excretion are
      characterized by elevated blood pressure and declining kidney function. In
      addition, such patients have a high risk of atherosclerotic vascular disease,
      proliferative retinopathy, and cardiomyopathy, suggesting that albuminuria is a
      marker of widespread vascular dysfunction. Increased transport of macromolecules
      across the vascular wall, elevated plasma levels of von Willebrand factor, and
      impaired fibrinolytic capacity have been demonstrated in albuminuric patients.
      The cause of this vascular vulnerability in susceptible patients is unknown, but
      increasing evidence has suggested that loss of the proteoglycan heparan sulfate
      in the vasculature may explain the widespread nature of the disease. Heparan
      sulfate is important for the glomerular endothelial cell and basement membrane
      charge densities, the anticoagulant properties of the vessel wall, and the growth
      regulation of intimal smooth muscle cells. Recent studies have shown that heparin
      increases the biosynthesis of heparan sulfate in endothelial cell cultures and
      prevents the characteristic glomerular basement membrane thickening when given to
      diabetic rats. Moreover, heparin has been shown to reduce albuminuria in patients
      with incipient diabetic nephropathy. Although increasing evidence supports the
      hypothesis that loss of heparan sulfate may play a pathophysiological role in the
      development of diabetic vascular complications, there are still many unresolved
      problems. What are the mechanisms of action of glycosaminoglycans at the
      molecular biology level, and how can we select compounds without anticoagulant
      activity suitable for long-term use in the prevention and treatment of late
      diabetic complications?

PMID- 9285509
TI  - Blood glucose control and microvascular and macrovascular complications in
      diabetes.
AB  - High blood glucose levels for several years is the major factor in the
      development and progression of microvascular complications in IDDM. Reducing mean
      blood glucose reduces the risk of progression of diabetic microvascular
      complications substantially. A curve-linear relationship exists between HbA1c
      levels and progression of diabetic retinopathy. Recent evidence also points to a
      close relationship between high blood glucose levels and progression of
      microvascular complications in NIDDM. The relationship between mean blood glucose
      and cardiovascular disease in diabetes has been unclear. Recent population-based
      studies give evidence for a linear association of glycemic control with the risk
      for cardiovascular disease in patients with NIDDM. However, randomized studies
      comparing different degrees of glycemic control in NIDDM and their impact on
      cardiovascular morbidity and mortality are urgently needed.

PMID- 9285510
TI  - How to protect the kidney in diabetic patients: with special reference to IDDM.
AB  - During the development to overt nephropathy, diabetic patients go through several
      characteristic stages of renal disease, moving from normo- to micro- to
      macroalbuminuria. Microalbuminuria is defined as a urinary albumin excretion
      between 20 and 200 microg/min; values <20 microg/min are designated as
      normoalbuminuria, and values >200 microg/min are designated as macroalbuminuria.
      Only with macroalbuminuria does the glomerular filtration rate (GFR) fall
      consistently. The decisive intermediary endpoints are postponement or prevention
      of micro/macroalbuminuria and reduction or prevention of the fall in GFR
      (stronger endpoint), with postponement of end-stage renal disease as a final
      endpoint. Good metabolic control can prevent or postpone the development of
      microalbuminuria, the earliest sign of diabetic renal disease. The ideal
      realistic therapeutic window may be an HbA1c value between 7 and 8.5% (mean
      reference value 5.5%). Thus, efforts should aimed at implementing the best
      possible control before the onset of microalbuminuria, with the other important
      aim of minimizing hypoglycemic side effects. In patients with microalbuminuria,
      blood pressure gradually increases, and early antihypertensive treatment becomes
      crucial. Good glycemic control (with the same glycemic goal as above) may be
      difficult to achieve in some of these patients, but it is still important. With
      overt nephropathy, defined as clinical proteinuria, a relentless decline in GFR
      is inflicted, unless patients are carefully treated with antihypertensive agents,
      often in combination therapy. Good metabolic control is still strongly warranted
      because patients with high HbA1c progress much more rapidly. The natural history
      of the rate of fall in GFR may be reduced from 12 to 3 ml x min(-1) x year(-1),
      but genetic factors may be involved; the ACE-genotype DD seems to progress more
      rapidly during treatment. Protein restriction is also of some interest. Early
      screening is recommended in all guidelines, with emphasis on testing for
      albuminuria, including microalbuminuria, along with careful control of glycemia
      and blood pressure.

PMID- 9285511
TI  - Role of modified lipoproteins in diabetic macroangiopathy.

PMID- 9285512
TI  - Blood vessel wall interactions in diabetes.

PMID- 9285513
TI  - Impaired coronary flow reserve in NIDDM: a possible role for diabetic cardiopathy
      in humans.
AB  - Diabetic cardiopathy represents a cardiac disorder with involvement of
      myocardial, interstitial, coronary, and neural structures. One of the main
      manifestations refers to coronary microangiopathy, which has not yet been clearly
      identified. Coronary hemodynamics, including the determination of coronary flow
      reserve, were therefore analyzed in normal subjects and in nine patients with
      NIDDM and clinically suspected coronary heart disease but normal coronary
      arteriogram. Coronary flow reserve was determined as the quotient of baseline and
      minimal coronary resistance after dipyridamole (0.5 mg/kg i.v.). Coronary blood
      flow was measured quantitatively by the argon method. Systolic left ventricular
      function was analyzed by ventriculography and diastolic function by M-mode and
      Doppler echocardiography. Twelve healthy normotensive subjects served as the
      control group (CON). In the diabetic patients, maximal coronary flow was
      significantly reduced (172 +/- 50 vs. 395 +/- 103 ml/min x 100 g; P < 0.001), and
      minimal coronary resistance was increased (0.60 +/- 0.19 vs. 0.24 +/- 0.06 mmHg x
      min x 100 g/ml; P < 0.001). Coronary reserve in the diabetic subjects was
      markedly reduced (1.84 +/- 0.39 vs. 4.23 +/- 0.52; P < 0.001). No difference
      existed with respect to myocardial oxygen consumption (12.4 +/- 2.3 vs. 11.8 +/-
      2.8 ml O2/100 g x min; NS). Global systolic function was normal in all patients
      (ejection fraction: NIDDM 72 +/- 13 vs. CON 77 +/- 12%, NS; CI: NIDDM 3.2 +/- 0.8
      vs. CON 3.3 +/- 1.2 l/min x m2, NS). Diastolic function was impaired in diabetic
      patients with an increase in relaxation time index (97 +/- 23 vs. 45 +/- 18 ms; P
      < 0.01) and an impaired diastolic inflow pattern, indicated by the ratio between
      early and late transmitral flow (0.75 +/- 0.14 vs. 1.66 +/- 0.13; P < 0.05). We
      conclude that the markedly reduced coronary flow reserve in diabetic patients may
      play a key role in the induction and perpetuation of coronary insufficiency in
      myocardial ischemia, in diastolic and systolic dysfunction, and in the initiation
      of diabetic cardiopathy.

PMID- 9285515
TI  - Pharmacological strategies to prevent macrovascular disease in NIDDM.
AB  - The pathogenesis of atherosclerosis and vascular thrombosis in NIDDM is reviewed.
      Evidence that suggests a role for chronic hyperglycemia, in association with
      other vascular risk markers, is presented. Based on this framework, a
      multifactorial approach to the prevention of progression of macrovascular disease
      in NIDDM is discussed. Results from a recent consensus conference sponsored by
      the American Diabetes Association regarding approaches to glycemic regulation in
      people with NIDDM are reviewed. It is concluded that preventive approaches will
      materially alter the course of macrovascular disease, reduce health care costs,
      and improve the quality of life for people with NIDDM.

PMID- 9285514
TI  - The role of nutritional modifications in the prevention of macrovascular
      complications of diabetes.
AB  - A wide range of dietary changes is likely to reduce the risk of macrovascular
      complications of diabetes. It is critically important to recommend a balance of
      macronutrients different from that currently consumed in most Western countries.
      Saturated fatty acids, especially myristic and palmitic acids, and trans fatty
      acids must be reduced to lower LDL cholesterol. Intake of polyunsaturated fatty
      acids should not be excessive (less than 10% total energy). Fiber-rich
      carbohydrate, derived from cereals, vegetables, and fruit with intact cell walls,
      and cis monounsaturated fatty acids should provide the bulk of total energy.
      These changes are likely to be associated with the most favorable lipoprotein
      profile and increase intake of dietary antioxidants and so reduce the level of
      oxidative stress. A reduction of sodium to below 6 g per day will help to reduce
      blood pressure levels. Optimal glycemic control has not yet been proved to reduce
      the risk of macrovascular complications, though this is a desirable goal for many
      other reasons. Ensuring appropriate energy balance (so that BMI is within the
      desirable range), using low glycemic index foods, and appropriately balancing
      carbohydrate intake with hypoglycemic drug therapy provide the best nutritional
      means of achieving satisfactory blood glucose levels. Successful implementation
      of nutritional recommendations requires the availability of dietitians capable of
      translating appropriate nutrition into appropriate foods acceptable to people
      with diabetes and their families. Clear food labeling and the availability of
      appropriate manufactured foods will further help patients with diabetes to
      achieve the dietary recommendations.

PMID- 9285516
TI  - Transport of protein kinase C isoforms to the nucleus of PC12 cells by nerve
      growth factor: association of atypical zeta-PKC with the nuclear matrix.
AB  - In an effort to understand the role of protein kinase C (PKC) in nerve growth
      factor-induced differentiation, we studied the expression of PKC using isoform
      specific antibodies. Western blot analysis on whole cell lysates showed that
      alpha,beta,gamma,epsilon,zeta, iota/lambda and mu were expressed in PC12 cells,
      except for theta which was absent. In nuclei obtained from control PC12 cells,
      small amounts of delta, epsilon, iota/lambda and zeta were detected. A computer
      assisted search algorithm was used to search for the presence of bipartite
      nuclear targeting motifs. In classical PKC isoforms alpha,beta,gamma, two
      bipartite motifs were present, while atypical iota/lambda and zeta-PKC displayed
      one motif, whereas novel PKC isoforms did not exhibit any bipartite motif
      structure. Treatment of cells with differentiating doses of nerve growth factor
      (NGF) resulted in changes of differential magnitude for all of the nuclear PKC
      isoforms in response to NGF. However, little change in gamma-PKC was observed in
      response to NGF. This analysis indicated that other factors may contribute to
      transport of PKC into the nucleus, in addition to the bipartite motif itself.
      Atypical zeta-PKC is required for NGF-induced neurite outgrowth of PC12 cells
      (Coleman and Wooten: J Mol Neurosci 5:39-57, 1994). Increases in nuclear zeta-PKC
      were NGF dose-dependant with a concomitant decrease in cytoplasmic
      immunoreactivity. The localization of zeta-PKC was investigated by means of
      immunoelectron microscopy which revealed the localization of this isoform within
      the inner nuclear matrix bound to chromatin. Taken together, these findings
      suggest that zeta-PKC may be involved in the regulation of nuclear processes.

PMID- 9285517
TI  - FGF plays a subtle role in oligodendrocyte maintenance in vivo.
AB  - Numerous in vitro studies indicate that fibroblast growth factors (FGFs) play a
      role in both the development and maintenance of oligodendrocytes. Addition of FGF
      to mature oligodendrocytes in culture was reported to downregulate the expression
      of genes encoding proteins of the myelin sheath and to induce a loss of myelin
      compaction. In this study, a model was developed to functionally block FGF
      signaling in oligodendrocytes in vivo, by generating transgenic mice expressing a
      dominant-negative FGF receptor (FGFR1), under the control of the myelin basic
      protein (MBP) promoter. To demonstrate the effectiveness of this model, truncated
      FGFR1 was first overexpressed in an FGF-responsive cell line in vitro. It was
      confirmed that FGF-signalling was blocked in these cells. Subsequently, five
      independent transgenic lines ("MBP-FRD") were generated. Three lines expressing
      the highest level of the transgene were further studied. Initial investigation by
      Western blot and light microscopic analyses revealed no apparent alterations in
      myelination of the MBP-FRD mouse brains. However, ultrastructural analysis of
      myelinated optic nerve fibres from two independent MBP-FRD lines revealed a
      significant increase in myelin thickness as a function of fibre diameter for both
      transgenic lines (13% and 16% increase). This increase in myelin thickness was
      not accompanied by alterations in myelin compaction. These results support the
      idea that FGF signaling in oligodendrocytes plays a role in the modulation of
      axon myelination in vivo.

PMID- 9285518
TI  - Stimulus-secretion coupling in porcine adrenal chromaffin cells: effect of
      dexamethasone.
AB  - Recent studies from this laboratory established that dexamethasone (DEX)
      potentiates Ca2+ current via voltage-gated Ca2+ channels (VGCC), and as a
      consequence potentiates agonist-induced cytosolic Ca2+ transients in rat adrenal
      chromaffin cells. The present study examined whether DEX can also modulate VGCC
      activity and agonist-induced cytosolic Ca2+ transients in porcine adrenal
      medullary chromaffin (PAMC) cells, and if so whether this results in alterations
      in catecholamine secretion. Forty-eight-hr exposure to 1 microM DEX significantly
      increased peak Ca2+ current (delta + 138%; n = 6; P < 0.05) in PAMC cells. DEX
      treatment also significantly potentiated the increase in cytosolic Ca2+ in
      response to membrane depolarization with KCl (delta + 20%; n = 29; P < 0.05), but
      did not affect the amplitude of Ca2+ transients elicited by nicotine or
      acetylcholine. Despite the potentiation of intracellular Ca2+, DEX treatment had
      no effect on KCl-induced secretion of either norepinephrine or epinephrine. These
      data demonstrate that as in the rat chromaffin cell, DEX can also increase VGCC
      activity in PAMC cells. However, the subsequent potentiation of selected agonist
      induced increases in intracellular Ca2+ does not appear to be sufficient to alter
      catecholamine secretion.

PMID- 9285520
TI  - Tenascin-C expression and axonal sprouting following injury to the spinal dorsal
      columns in the adult rat.
AB  - We have examined the expression and distribution of the extracellular matrix
      molecule tenascin-C in and around lesions of the thoracic dorsal columns in adult
      rats 3 days to 8 weeks after injury, using in situ hybridization,
      immunofluorescence, electron microscopy and immunoelectron microscopy. Numerous
      tenascin-C mRNA+ cells were present in and around the lesion at 3 days; fewer
      were present at 14 days and almost none 30 days after injury. Most tenascin-C
      mRNA+ cells in the spinal cord around the lesion were GFAP+, but most of those
      within the lesion were not, suggesting that tenascin-C is produced in the injured
      spinal cord by a subpopulation of astrocytes and by other cells that invade the
      lesion; these cells may include meningeal cells, macrophages, and Schwann cells.
      From 3 to 30 days after injury, heavy tenascin-C immunoreactivity was present at
      the lesion site (especially transections), and there was lighter immunoreactivity
      around the lesion and in the degenerating dorsal column. The heaviest
      immunoreactivity was associated with collagen fibrils in areas of expanded
      extracellular space and with basal laminae (covering Schwann cells and some
      astrocytes) but tenascin-C was also found close to the surfaces of some OX-42 +
      macrophages/microglia, leptomeningeal cells, and capillaries. Neurofilament (NF)+
      axons grew into the highly tenascin-C-immunoreactive lesion sites, indicating
      that tenascin-C does not prevent axonal growth into these areas. However, such
      axons were not coated with tenascin-C except where directly exposed to the
      extracellular space.

PMID- 9285519
TI  - Axonal regrowth through collagen tubes bridging the spinal cord to nerve roots.
AB  - The capacity of central nervous system (CNS) axons to elongate from the spinal
      cord to the periphery throughout a tubular implant joining the ventral horn of
      the spinal cord to an avulsed root was investigated in a model of brachial plexus
      injury. The C5-C7 roots were avulsed by controlled traction and the C6 root was
      bridged to the spinal cord over a 3 mm gap by the use of a collagen cylinder
      containing or not containing an autologous nerve segment, or an autologous nerve
      graft. Nine months later, the functionality and the quality of the axonal
      regrowth was evaluated by electrophysiology, retrograde labelling of neurons, and
      histological examination of the gap area. A normal electromyogram of the biceps
      was observed in all animals where the C6 root was bridged to the spinal cord. The
      mean average amplitude of the motor evoked potentials was comprised between 17.51
      +/- 12.03 microV in animals repaired with a collagen cylinder, and 27.83 +/-
      22.62 microV when a nerve segment was introduced in the tube. In nonrepaired
      animals spontaneous potentials reflecting a muscle denervation were observed at
      electromyography. Retrograde labelling indicated that a mean number of 58.88 +/-
      37.89 spinal cord neurons have reinnervated the biceps in animals repaired with a
      tube versus 78.38 +/- 62.11 when a nerve segment was introduced in the channel,
      and 97.25 +/- 56.23 in nerve grafting experiments. Analyses of the repair site
      showed the presence of numerous myelinated regenerating axons. In conclusion, our
      results indicate that spinal cord neurons can regenerate through tubular implants
      over a 3 mm gap, and that this axonal regrowth appeared as effective as in nerve
      grafting experiments. The combination of an implant and a nerve segment did not
      significantly increase the regeneration rate.

PMID- 9285521
TI  - Vascular endothelial growth factor (vascular permeability factor) expression in
      injured rat brain.
AB  - We investigated the expression of vascular endothelial growth factor
      (VEGF)/vascular permeability factor (VPF) in stab and freeze brain injury models
      in rats. Immunohistochemical staining with anti-VEGF antibodies demonstrated an
      increase in VEGF-positive cells in and around both lesions. Morphologically, the
      injury-induced VEGF-positive cells resembled astrocytes. Double immunofluorescent
      staining for the astrocytic marker glial fibrillary acidic protein (GFAP) and
      VEGF demonstrated directly that VEGF-positive cells which appeared in response to
      these injuries were astrocytes. VEGF expression in astrocytes was maximal on days
      3 and 4 after injury in terms of both cell number and affected area. The increase
      in VEGF-positive cells was more widespread in the freeze lesion than in the stab
      wound, and occurred in both the lesioned and nonlesioned hemispheres. VEGF
      positive cells were still present 3 weeks after both injuries, but their numbers
      were reduced and their distribution became limited to the immediate vicinity of
      the lesions. These observations indicate that astrocytes react to injury by
      increasing VEGF expression, suggesting that VEGF might participate in the central
      nervous system response to injury.

PMID- 9285523
TI  - Transforming growth factor-beta2 selectively alters the developmental expression
      of the fast transient A-current in cultured rat superior cervical ganglion
      neurons.
AB  - Cultures of neonatal rat superior cervical ganglion (SCG) were utilized to
      examine the ability of transforming growth factor-beta2 (TGFbeta2) to alter
      voltage-gated K+ channel development. Whole-cell patch clamp recordings were used
      to monitor changes in three separate K+ currents: A rapidly inactivating A
      current (I(Af)), a slowly inactivating A-current (I(As)), and a non-inactivating
      current (I(K)). Continuous TGFbeta2 (10 ng/ml) treatment selectively altered the
      normal developmental decrease in I(Af) expression in SCG neurons, but did not
      significantly change I(As) or I(K) expression. After 2 weeks of treatment, the
      mean I(Af) current density in control cultures had decreased 67%, while the I(Af)
      current density in TGFbeta2 treated cultures remained near initial values
      (approximately 2.7-fold higher than control). This difference remained even after
      4 weeks of exposure. TGFbeta2 did not appear to change the activation kinetics or
      voltage-dependence of I(Af). These findings indicate that TGFbeta2 may play an
      important role in modulating the development of neuronal excitability by
      regulating the expression of voltage-gated K+ channels.

PMID- 9285522
TI  - Different mechanisms for inhibition of cell proliferation via cell cycle proteins
      in PC12 cells by nerve growth factor and staurosporine.
AB  - PC12 cells have previously been shown to cease cell division during nerve growth
      factor (NGF)-induced differentiation by affecting specific cell cycle proteins.
      Staurosporine, a protein kinase inhibitor, also causes PC12 cell differentiation,
      independently of neurotrophins or plasma membrane receptors. We have investigated
      the relationship of the tumor suppressor protein, p53, and other cell cycle
      proteins to the antiproliferative effects of NGF and staurosporine in PC12 cells.
      NGF treatment of PC12 cells stimulated an increase of p53 protein in the nucleus
      and, more slowly, an increase in total cellular p53 protein. Levels of the cyclin
      kinase inhibitor p21/WAF1, cyclin D1, and cyclin G, all downstream
      transcriptional targets of p53, increased after short times of NGF treatment.
      Cessation of replication and differentiation occurred more rapidly in defined
      medium (2 days) than in serum medium (6 days), in correspondence with the more
      rapid changes in both p53 and p21/WAF1 levels in defined medium (1 hour) than in
      serum (1 day). Levels of p34cdc2 and p33cdk2 kinase dropped after 6 to 10 days
      treatment with NGF in serum, close to the time of terminal differentiation.
      Staurosporine, on the other hand, inhibited DNA replication of PC12 cells in a
      time- and dose-dependent fashion by affecting cyclin-dependent kinases.
      Staurosporine had no effect on the protein levels of p53, p21/WAF1, or cyclin G.
      The kinase activity of both p34cdc2 and p33cdk2 were inhibited in vitro with IC50
      values of 20 nM and 75 nM, respectively. In vivo p34cdc2 kinase activity was
      inhibited within 1 day, before the decrease in the levels of p34cdc2 protein at
      days 2 to 3. In contrast, in vivo p33cdk2 kinase activity only decreased in
      concert with protein levels. Although both NGF and staurosporine inhibit DNA
      replication concomitant with induction of differentiation by affecting the
      activity of p34cdc2 and p33cdk2, the mechanism of the two agents is quite
      different. NGF achieves inhibition of activity of these cyclin-dependent kinases
      by signalling through the TrkA receptor to the tumor suppressor protein p53 and
      then to p21/WAF1. In contrast, staurosporine directly inhibits the activity of
      p34cdc2 and p33cdk2 by binding to them and also indirectly by alteration of their
      phosphorylation through other regulatory kinases.

PMID- 9285525
TI  - Measurement of the rate of myelination using a fluorescent analogue of ceramide.
AB  - Fluorescence digital imaging microscopy was used to investigate the process of
      myelin formation by Schwann cells in neuronal cocultures. The uptake of the
      fluorescent ceramide analogue N-[5-(5,7-dimethyl BODIPY)-1-pentanoyl]D-erythro
      sphingosine (C5-DMB-ceramide) and its return to the plasma membrane as the
      corresponding fluorescent sphingomyelin and galactocerebroside analogues were
      measured. Through observation of this process it was possible to determine the
      rate of lipid synthesis in myelin internodes. The highest rate of synthesis of
      fluorescent sphingomyelin and galactocerebroside analogues was observed between
      days 3 and 7 after induction of myelination. This rate was approximately 5-fold
      greater than the steady-state rate of synthesis in fully myelinated internodes
      and 10-fold higher than the rate observed prior to myelination. The internode
      diameter increased during the first 3 days of myelination, but this was followed
      by a reduction in diameter and then an increase until the myelin sheath formation
      was completed. Internodes were found to be heterogeneous in terms of lipid
      distribution, with fluorescence intensities ranging 5-fold in myelinating
      cultures. Additionally, the rate of lipid transport along the internode was slow
      since there was a quicker increase in fluorescence intensity near the cell body
      of the Schwann cell than near the nodes of Ranvier. The results show that
      fluorescence digital imaging microscopy can be used to study the process of
      myelin formation and to determine the rate of formation, lipid transport, and
      heterogeneity of the myelin membrane.

PMID- 9285524
TI  - Factors that contribute to the transneuronal spread of herpes simplex virus.
AB  - In viral encephalitis and retinal necrosis, different herpes simplex virus (HSV)
      strains spread between neurons in the central nervous system (CNS) by distinctly
      different routes. The steps of viral infection and spread in a single neuron type
      and nearby glial cells in vivo have been determined for three different strains
      of HSV (F, H129, and McIntyre-B). The corneas of mice were inoculated with
      equivalent titers of the strains. Two to 5 days later, the animals were killed.
      The spread of viral proteins within trigeminal cells was examined using immuno-
      and electron microscopy and Western blots with anti-HSV polyclonal antiserum.
      McIntyre-B virus infection resulted in fewer labeled ganglion cells, possibly as
      a result of reduced viral production in the corneal epithelium or trigeminal
      ganglion cells. Although the McIntyre-B strain was at least as, if not more
      efficient, at retrograde transport than the other strains, the amount of McIntyre
      B virus that was transported in the trigeminal roots in an anterograde direction
      was significantly less than the other strains. Uptake by ganglionic satellite
      cells was qualitatively similar for the three strains, but maturation and release
      of virus from satellite cells to other neurons were reduced in the McIntyre-B
      strain. These characteristics may account for the preferential retrograde
      transneuronal spread of McIntyre-B strain.

PMID- 9285526
TI  - Effects of sodium chloride, Triton X-100, and alkaline pH on the measurable
      contents and sedimentability of the nerve growth factor (NGF) antigen in adult
      rat hippocampal tissue extracts.
AB  - Nerve growth factor (NGF) was found to be largely associated with sedimentable
      fractions of hippocampal and other neural tissues of the adult rat (Hoener et
      al.: Brain Res 728:47-56, 1996), verified by both bioassay and ELISA techniques.
      In the present study, the ELISA assay conditions were improved and simplified.
      Bovine serum albumin was needed in the phosphate buffered saline for maximal
      measurability of NGF antigen. Hippocampal tissue sonicates were separated into
      nonsedimentable supernatant and sedimentable pellet fractions. Individual or
      combined treatments with sodium chloride, Triton X-100, and pH were applied to
      the samples for possible effects on the i) measurable content of NGF antigen and
      ii) distribution of sedimentable and nonsedimentable forms. The amount of
      measurable NGF antigen was found to be increased in a dose dependent fashion by
      sodium chloride between 0.15 and 0.35 M, Triton X-100 between 0 and 0.5%, and pH
      between 8.5 and 10.5. The same treatment that led to maximal measurable NGF
      levels (0.7% Triton X-100 and pH 10.5) also caused the release of the NGF antigen
      from sedimentable to nonsedimentable fractions. Similar findings regarding
      maximal NGF antigen levels and release were seen for treatments applied to the
      sonicate before separation into a supernatant and pellet fraction.

PMID- 9285527
TI  - The carboxyl-terminal cytoplasmic domain of CD36 is required for oxidized low
      density lipoprotein modulation of NF-kappaB activity by tumor necrosis factor
      alpha.
AB  - The binding of oxidized low-density lipoprotein (Ox LDL) by monocyte-macrophages
      causes pleiotropic effects, including changes in gene expression, and is thought
      to represent an early event in atherogenesis. The integral membrane glycoprotein
      CD36 appears to play a physiological role in binding and uptake of Ox LDL by
      monocyte-macrophages, although the molecular events associated with CD36-Ox LDL
      interaction are unknown. To approach this issue, we used CD36 transfected Chinese
      hampster ovary (CHO) cells, exposed them to Ox LDL, and determined changes in the
      activity of the transcription factor NF-kappaB. We report here that Ox LDL
      enhanced DNA binding activity of nuclear extracts to an NF-kappaB sequence
      following activation of CD36-producing CHO cells with the proinflammatory
      cytokine tumor necrosis factor-alpha (TNF-alpha). This enhanced DNA binding
      activity was inhibited by coincubation of CD36 transfected cells with the human
      CD36-specific antibody OKM5. We also determined that activation of NF-kappaB DNA
      binding activity required an intact carboxyl-terminal cytoplasmic segment on
      CD36. Our results support the idea that human CD36 mediates signal transduction
      events in response to Ox LDL.

PMID- 9285528
TI  - Adenosine 3',5'-cyclic monophosphate/vanadate-sensitive phosphorylation of DARPP
      32- and inhibitor-1-immunoreactive proteins.
AB  - Among the cellular actions of vanadate ions are several that have the potential
      to be of significance in the regulation of protein phosphorylation. The effects
      of vanadate on adenosine 3',5' cyclic monophosphate (cAMP)-dependent and
      independent, alkali-resistant protein phosphorylation in a synaptosomal
      preparation from rat cortex were examined in this study. Three major vanadate
      stimulated, cAMP-independent phosphoproteins (58-, 50-, and 39-kDa) and two cAMP
      dependent species (37- and 32-kDa) were detectable. The potentiation between
      vanadate and cAMP in stimulating the phosphorylation of the latter two proteins
      is in contrast to the nonadditive combined effect of both on the phosphorylation
      of other synaptosomal proteins. The two cAMP-dependent, 32P-labeled proteins
      possess identical or very similar physicochemical properties to two previously
      cited neuronal phosphoproteins, namely, dopamine- and adenosine 3',5'
      monophosphate-regulated phosphoprotein-32 (DARPP-32) and inhibitor-1 (I-1). Such
      properties include phosphorylation by cAMP-dependent protein kinase, the presence
      of an alkali-resistant phosphothreonine residue, comigration on two-dimensional
      gel electrophoresis, dephosphorylation by type-2B protein phosphatase, and
      crossreactivity with specific antibodies. Costimulation by cAMP and vanadate of
      phosphorylation of the latter two proteins on threonine residues, at
      concentrations of vanadate consistent with the regulation of protein tyrosine
      phosphatase activity, indicates a unique interaction between these two regulators
      of protein phosphorylation at the nerve terminus.

PMID- 9285529
TI  - A novel receptor mediated ATP transport system regulated by tyrosine and
      serine/threonine phosphokinases in Trypanosoma cruzi trypomastigotes.
AB  - Trypanosoma cruzi has a plasma membrane ATP transport system that may consist of
      an exterior receptor domain (ATP-R) and an interior domain regulated by tyrosine
      and serine/threonine kinases. The addition of exogenous ATP to freely swimming
      trypomastigotes resulted in a receptor-mediated inward movement of the
      nucleotide, and the system obeyed mass action law (Km, 9.42 microM and Vmax, 77.7
      nmol x min(-1) x 4 x 10(6) trypomastigotes(-1)). Preloaded [3H]ADPi was not
      exchanged for ATP following the addition of increasing concentrations of
      exogenous ATPo to swimming trypomastigotes. Trypomastigote [ATP]o <--> ATP-R -->
      [ATP]i transport was [ATP]o-dependent and saturable at 100 microM. [ATP]o <-->
      ATP-R --> [ATP]i transport was abrogated by the tyrosine kinase inhibitors,
      genistein and lavendustin A. [ATP]o <--> ATP-R --> [ATP]i transport was also
      inhibited by the serine/threonine kinase inhibitor, staurosporin. Suramin, the
      antagonist of P2x and P2y purinergic receptors and the inhibitor of tyrosine
      kinase growth factor receptors, was also a very effective competitive inhibitor
      of the trypomastigote ATP transport system. The action of exogenous
      [gamma32P]ATPo resulted in the initial and simultaneous phosphorylation of a 63
      kDa polypeptide (p63) and of a 92.4-kDa polypeptide (p92.4), which was followed
      by the abrupt phosphorylation of many other substrate proteins. The
      trypomastigote p63/p92.4 polypeptides may represent substrate proteins of a
      putative ATP-R-related tyrosine phosphokinase, and ATP receptors may transmit
      their signals by phosphorylation of specific substrate proteins.

PMID- 9285530
TI  - In vivo autoradiographic competition studies of isomers of [125I]IQNP against QNB
      demonstrating in vivo m2 muscarinic subtype selectivity for QNB.
AB  - (R,S)-[125I]IQNB has been used extensively in in vivo studies in rats, and has
      been of utility in demonstrating the in vivo subtype selectivity of
      nonradioactive ligands in competition studies. Because of the implications for
      the study of Alzheimer's disease (AD), those ligands that demonstrate m2
      selectivity are of particular interest. Radiolabelled Z- and E-(-,-)-1
      azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha
      phenylacetate (Z- and E-(-,-)-[125I]IQNP) are analogs of (R,S)-[125I]IQNB. Rat
      brain regional dissection studies and in vivo autoradiographic comparison of the
      time-courses of (R,S)-[125I]IQNB, Z-(-,-)-[125I]IQNP, and E-(-,-)-[125I]IQNP have
      indicated that Z- and E-(-,-)-[125I]IQNP, in general, are distributed similarly
      to (R,S)-[125I]IQNB. Z-(-,-)-[125I]IQNP binds to the muscarinic receptors in
      those brain regions enriched in the m2 subtype with approximately a two- to
      fivefold higher % dose/g compared with (R,S)-[125I]IQNB. Thus, as we show here
      autoradiographically, using QNB as the competing nonradioactive ligand in in vivo
      competition studies against Z-(-,-)-[125I]IQNP provides a sensitive and accurate
      probe for demonstrating the in vivo m2 selectivity of nonradioactive ligands.

PMID- 9285533
TI  - Comparative acute toxicity and primary irritancy of the ethylidene and vinyl
      isomers of norbornene.
AB  - The acute toxicity and primary irritancy of the industrial chemicals 5-ethylidene
      2-norbornene (ENB) and 5-vinyl-2-norbornene (VNB) were studied. They are of
      moderate acute peroral toxicity in the rat, with LD50 values for ENB of 2.54
      (male) and 5.66 (female) ml kg(-1), and for VNB of 5.90 (male) and 11.9 (female)
      ml kg(-1). Percutaneous toxicity is slight in the rabbit by 24-h occluded
      contact, with no mortalities for ENB up to 8.0 ml kg(-1) and only one mortality
      (male) at 16.0 ml kg(-1) VNB. Dynamically generated saturated vapor atmosphere
      LT50 values for ENB in the rat were 75 (male) and 125 (female) min, and for VNB
      they were 28 (male) and 37 (female) min. The 4-h LC50 values for ENB were 2717
      (male) and 3015 (female) ppm, and for VNB they were 2231 (male) and 2518 (female)
      ppm. Intravenously, the ENB LD50 ranged from 0.09 (male rabbit) to 0.11 ml kg(-1)
      (female); corresponding LD50 values for VNB were 0.10-0.05 mg kg(-1). Acute
      neurotoxic signs were seen by the intravenous and inhalation routes of exposure,
      including tremors, ataxia and convulsions; the latter were sufficient to cause
      vertebral column luxation or fracture, producing spinal cord compression and
      resultant hindlimb paralysis. Both ENB and VNB are moderately irritating to the
      skin (rabbit), causing erythema and edema, but not necrosis. Both materials cause
      slight conjunctival hyperemia and chemosis in rabbits, but not corneal injury.

PMID- 9285531
TI  - Expression of functional alpha2-adrenergic receptor subtypes in human corpus
      cavernosum and in cultured trabecular smooth muscle cells.
AB  - In this study, we have identified and characterized functional alpha2-adrenergic
      receptor (alpha2-AR) subtypes in human corpus cavernosum and in cultured human
      corpus cavernosum smooth muscle cells. Analysis of total RNA, isolated from whole
      corpus cavernosum tissue and smooth muscle cells, by RNase protection assays,
      demonstrated expression of mRNA for alpha2A, alpha2B, and alpha2C adrenergic
      receptor subtypes in whole tissue and alpha2A and alpha2C subtypes in cultured
      smooth muscle cells. Binding studies with [3H]RX821002 (a highly selective and
      specific ligand for alpha2-adrenergic receptor) in isolated membrane fractions of
      human corpus cavernosum smooth muscle cells, demonstrated specific alpha2-AR
      binding sites with high affinity (Kd = 0.63 nM) and limited capacity (25-30
      fmol/mg protein). Binding of [3H]RX821002 was displaced with the nonselective
      alpha-AR antagonist, phentolamine, and with the alpha-AR agonist, norepinephrine,
      in a dose-dependent manner, but not by the selective alpha1-AR agonist,
      phenylephrine. Binding of [3H]rauwolscine was also displaced by phentolamine. UK
      14,304, a selective alpha2-AR agonist, inhibited forskolin-induced cyclic
      adenosine monophosphate (cAMP) synthesis in cultured human corpus cavernosum
      smooth muscle cells and induced dose-dependent contractions of tissue strips in
      organ bath chambers. UK 14,304-induced contractions were inhibited with alpha2-AR
      selective antagonists, rauwolscine and delquamine (RS 15385-197). These
      observations suggest that in human corpus cavernosum, norepinephrine (NE) and
      epinephrine may activate postsynaptic alpha2-AR subtypes, in addition to
      activating alpha1-AR subtypes, on smooth muscle cells, contributing to local
      control of human corpus cavernosum smooth muscle tone, in vivo.

PMID- 9285534
TI  - Developmental effects of di-n-butyl phthalate after a single administration in
      rats.
AB  - The objective of this study was to determine the susceptible day for the
      developmental toxicity of di-n-butyl phthalate (DBP). Pregnant rats were given a
      single dose of DBP by gastric intubation at 1500 mg kg(-1) on one of days 6-16 of
      pregnancy. A significant increase in the incidence of postimplantation loss was
      found in pregnant rats given DBP on one of days 6-16, except for days 7 and 11.
      Significant increases in the incidences of fetuses with skeletal malformations,
      of fetuses with skeletal and internal malformations and of fetuses with external
      and skeletal malformations were noted after a single dosing of DBP on day 8, on
      day 9 and on day 15, respectively. Deformity of the cervical vertebrae was
      frequently observed after administration of DBP on day 8. Deformity of the
      cervical and thoracic vertebrae and ribs and dilatation of the renal pelvis were
      predominantly found in fetuses of dams treated with DBP on day 9. Cleft palate
      and fusion of the sternebrae were exclusively detected after administration of
      DBP on day 15. It could be concluded that the manifestation of deviant
      development induced by DBP varies with the developmental stage at the time of
      administration and that DBP induces two discrete responses from embryos to
      teratogenicity on days 8 and 9 and on day 15 of pregnancy.

PMID- 9285532
TI  - Short-term and subchronic repeated exposure studies with 5-ethylidene-2
      norbornene vapor in the rat.
AB  - 5-Ethylidene-2-norbornene (ENB) is an industrial chemical whose physical
      properties indicate a likelihood for vapor exposure to humans. The potential for
      target organ or cumulative toxicity was investigated in rats exposed for 6 h per
      day for 9 days over an 11-day period, or 66 or 67 days over 14 weeks; 4- week
      recovery animals were added to the 14-week study. Mean analytically measured ENB
      vapor concentrations (+/-SD) were 52 +/- 1.5, 148 +/- 2.3 and 359 +/- 4.2 ppm for
      the 9-day study and 4.9 +/- 0.14, 24.8 +/- 1.23 and 149 +/- 4.40 ppm for the
      subchronic study. There were no mortalities, and clinical signs were limited to
      periocular swelling and/or encrustation, and urogenital area wetness. Body weight
      gain was decreased in the 9-day 359 ppm females and in the subchronic 24.8 and
      149 ppm males. A minimal macrocytic anemia was present in subchronically exposed
      males, which resolved during the recovery period. In the 9-day study increased
      liver weight was associated with minimal centrilobular hepatocytomegaly and
      cytoplasmic basophilia with no degenerative or serum biochemical liver function
      changes, suggesting an adaptive response. Only relative liver weights were
      increased in the subchronic 149 ppm males, and no histopathological findings were
      observed. Principal target organ effects were to the thyroid gland, which showed
      an exposure concentration-related, but not exposure time-related, depletion of
      follicular colloid that resolved during the recovery period, together with light
      microscopic evidence for a hypertrophic and hyperplastic response in the
      follicular epithelium that resolved more slowly. The thyroid colloid depletion
      was a graded effect without a clear no-effect concentration, but was not
      accompanied by any clinical or clear biochemical evidence for thyroid
      dysfunction. A no-effect concentration of 4.9 ppm was established for the
      follicular cytological effects.

PMID- 9285535
TI  - Pyrethroid decrease in central nervous system from nerve agent pretreatment.
AB  - We studied the effect of pyridostigmine bromide, a nerve agent prophylactic, on
      the central nervous system (CNS) uptake of [14C]permethrin, a pyrethroid
      insecticide, at scaled human-equivalent exposures in rats using accelerator mass
      spectrometry (AMS). AMS detects 14C at attomole sensitivities and determines the
      tissue distribution of 14C-labeled compounds. Pyridostigmine bromide in chow at
      7.75 mg kg(-1) per day lowered the CNS tissue levels of permethrin, dosed at 4.75
      microg kg(-1), in the CNS of rats by 30%. These results are inconsistent with
      hypothesized synergy of such compounds as a precursor to 'Gulf War syndrome'.

PMID- 9285537
TI  - Millimeter wave-induced vibrational modes in DNA as a possible alternative to
      animal tests to probe for carcinogenic mutations.
AB  - Developing methods for alternative testing is increasingly important due to
      dwindling funding resources and increasing costs associated with animal testing
      and legislation. We propose to test the feasibility of a new and novel method for
      detecting DNA mutagenesis using millimeter wave spectroscopy. Although millimeter
      wave spectroscopy has been known since the 1950s, the cost was prohibitive and
      studies did not extend to large biological proteins such as DNA. Recent advances
      have made this technology feasible for developing laboratory and field equipment.
      We present preliminary findings for lesion-induced vibrational modes in DNA
      observed from 80 to 1000 gigahertz (GHz). These findings suggest that there are
      vibrational modes that can be used as identification resonances. These modes are
      associated with localized defects of the DNA polymers. They are unique for each
      defect/lesion, and should be easy to detect. We described a field-detecting
      detector based on the local modes.

PMID- 9285536
TI  - Neurotoxicological evaluation of ethyl tertiary-butyl ether following subchronic
      (90-day) inhalation in the Fischer 344 rat.
AB  - The purpose of this study was to evaluate whether repeated 6-h exposure (65
      exposures over a 14- week period) of male and female Fischer-344 rats (n = 12
      rats/sex/concentration) to ethyl tertiary-butyl ether (ETBE) atmospheres at 500,
      1750, or 5000 ppm would result in neurotoxicity. Neurotoxicity was assessed by a
      blinded functional observational battery (FOB), motor activity, and terminal
      neuropathology. Motor activity was assessed 4 days prior to ETBE exposure and
      following 20, 42, and 65 days of exposure. The FOB was assessed 4 days prior to
      ETBE exposure and following 1, 6, 10, 20, 42, and 65 days of exposure. Transient
      ataxia, a sign of narcosis, was noted in male rats immediately following the 6-h
      exposure to 5000 ppm ETBE. Statistically significant treatment effects on motor
      activity were not observed. Minor changes in grip strength and hindlimb splay
      were observed; however, none demonstrated a dose-response relationship or a
      consistent pattern of neurological dysfunction. No gross or microscopic
      abnormalities were observed in the central, peripheral, or autonomic nervous
      systems of rats exposed to 5000 ppm ETBE. No statistically significant
      differences in brain weight or size were observed in ETBE-exposed rats. A
      statistically significant increase in body weight was observed in female rats
      exposed to 5000 ppm following 42 and 65 exposure days. Although ataxia was a
      common feature of acute ETBE neurotoxicity in rats following high-level exposure,
      adverse neurological effects are not expected in the general public at the
      anticipated exposure levels associated with automotive refueling.

PMID- 9285538
TI  - Comparison of integrins in human skin, pig skin, and perfused skin: an in vitro
      skin toxicology model.
AB  - Integrins alpha2beta1, alpha3beta1, and alpha6beta4 are expressed in the
      epidermis, and play an important role in wound healing and/or epidermal-dermal
      interaction. These integrins may provide a new perspective into the understanding
      of wound healing and vesication. The isolated perfused porcine skin flap (IPPSF)
      has been shown to be an in vitro model for chemical-induced vesication. In order
      to determine whether the IPPSF could be utilized to study skin diseases mediated
      by integrins, the expression of integrins alpha2beta1, alpha3beta1, and
      alpha6beta4 was studied in human skin, pig skin, and the IPPSF using
      immunohistochemical staining. Immunostaining of both alpha2beta1 and alpha3beta1
      was primarily located at the periphery of the basal keratinocytes in human skin.
      Similarly, alpha2beta1 was expressed in the stratum basale layer of the epidermis
      in both pig skin and the IPPSF after 8 h of perfusion. These antibodies defined
      the periphery of the pig basal keratinocytes more diffusely than that of human
      cells. However, the alpha3 antibody outlined the keratinocytes in all epidermal
      layers of the IPPSF and in the pig skin. In human skin, pig skin, and the IPPSF,
      alpha6beta4 stained exclusively at the basal pole of the basal keratinocytes, and
      showed a continuous linear labeling along the epidermal-dermal junction. The
      IPPSF showed stronger immunoreactivity with the antibody against beta4.
      Furthermore, the distribution of alpha6beta4 in 5.0 mg/ml of bis-(2-chloroethyl)
      sulfide (sulfur mustard, HD)-induced blisters was examined in the IPPSF. The
      alpha6beta4 staining was exclusively located on the epidermal side (roof) of the
      blister. In addition, alpha6beta4 staining was not linear but disrupted and
      patchy. These findings suggest that any destruction of alpha6beta4 may weaken the
      epidermal-dermal junction, thereby leading to HD-induced vesication. This study
      demonstrates that the IPPSF expresses similar integrins to those of human skin,
      and the distribution of alpha6beta4 in the IPPSF blisters caused by HD is
      comparable to that of some human basement membrane blistering diseases.
      Therefore, the pig and the IPPSF prove to be ideal models to study the role of
      integrins in wound healing and blistering diseases occurring at the epidermal
      dermal junction.

PMID- 9285539
TI  - Neurochemical mechanisms in soman-induced seizures.
AB  - This study examined brain regional neurotransmitter level changes as a function
      of seizure duration following soman intoxication. Rats, implanted with cortical
      electrodes and pretreated with HI-6, received a convulsant dose of soman. At
      selected times after seizure onset the EEG recording electrodes were removed and
      the animal was killed. Spinal cord cholinesterase (ChE) activity was rapidly and
      maximally depressed, while brain acetylcholine (ACh) levels showed elevations as
      early as 3 min after soman treatment and reached significantly high levels at
      time of seizure onset. Norepinephrine (NE) levels decreased starting 5 min after
      seizure onset and continued to decline. Levels of dopamine (DA) and of its
      metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid were elevated as
      early as 5 min after seizure onset and thereafter. The brain levels of aspartate
      were markedly decreased at and after 20 min of seizures; levels of glutamate were
      depressed at 80 min in the cortex. Levels of gamma-aminobutyric acid (GABA) were
      significantly increased in the cortex starting at 20 min after seizure onset, and
      in the striatum and hippocampus at 80 min after onset. The levels of glutamine,
      glycine and taurine were not changed at any time studied. These findings are
      consistent with the notion that inhibition of ChE and elevation of ACh initiate
      the seizure process, resulting in secondary changes in DA turnover and release of
      NE, and later changes in excitatory (aspartate, glutamate) and inhibitory (GABA)
      amino acid transmitters.

PMID- 9285540
TI  - Detection of stromal cells in peripheral blood progenitor cell collections from
      breast cancer patients.
AB  - Transplantation of growth factor-mobilized peripheral blood progenitor cells
      (PBPC) is widely used in the treatment of several neoplastic diseases. While in
      PBPC harvests the presence of several accessory immune and tumor cells has been
      documented, that of stromal cells has not been reported. In the present study, we
      investigated for the presence of stromal cells in growth factor-mobilized PBPC
      harvests from breast cancer patients. Low-density cells from PBCP harvests in
      culture gave rise to an adherent layer containing fibroblast-like and large flat
      round cells. These cells express positive immunofluorescence staining for
      collagen I, collagen III, fibronectin, VCAM-1 (CD106), ICAM-1 (CD54) and
      mesenchymal antigens recognized by monoclonal antibodies, SH2 and SH3. PBPC
      derived stromal cells do not express antigens CD34, CD45 and CD14. Stromal cells
      were detected in the PBPC harvests of 11/14 patients (median 0.63%; range 0.02
      2.32) and their concentration correlates with the number of CD34+ cells in PBPC.

PMID- 9285541
TI  - Phase II study of high-dose cyclophosphamide, etoposide, and carboplatin (CEC)
      followed by autologous hematopoietic stem cell rescue in women with metastatic or
      high-risk non-metastatic breast cancer: multivariate analysis of factors
      affecting survival and engraftment.
AB  - Seventy women with high-risk stage II (n = 10), IIIA (n = 12), IIIB (n = 11), or
      IV (n = 37) breast cancer received cyclophosphamide 6000 mg/m2, etoposide 2400
      mg/m2, and carboplatin 1200 mg/m2 followed by infusion of autologous
      hematopoietic stem cells (AHSC). Women with high-risk stage II disease had eight
      or more involved axillary lymph nodes (n = 9) or axillary and breast relapse
      following lumpectomy, chemotherapy, and radiation therapy (n = 1). Women with
      measurable stage III or stage IV disease were required to demonstrate complete or
      partial response to conventional-dose chemotherapy prior to transplant. The
      overall (complete plus partial) response rate for the 31 patients not in complete
      remission at the time of transplant was 55%. With a median follow-up of 545 days,
      the 2-year actuarial progression-free survival rates for patients with stage II,
      IIIA, IIIB and IV are 86, 75, 42 and 13%, respectively. Factors independently
      predictive of longer progression-free survival by multivariate analysis included
      lower stage disease, status of disease at transplant (in CR vs not in CR), and
      positive estrogen receptor status. Factors predictive of more rapid neutrophil
      engraftment by multivariate analysis included post-transplant administration of
      hematopoietic growth factors, greater number of infused CFU-GM, mobilization with
      G-CSF or cyclophosphamide/G-CSF (vs mobilization with GM-CSF or no mobilization),
      and lower stage disease. Only one patient (1.4%) died prior to day 100 from any
      cause. High-dose cyclophosphamide, etoposide, and carboplatin followed by
      infusion of AHSC constitutes an active and well-tolerated regimen in the
      treatment of women with high-risk non-metastatic or metastatic breast cancer.

PMID- 9285542
TI  - Autologous stem cell transplantation for poor prognosis Hodgkin's disease in
      first complete remission: a retrospective study from the Spanish GEL-TAMO
      cooperative group.
AB  - Although more than 50% of Hodgkin's disease patients are cured with conventional
      chemotherapy, many will relapse and eventually die from their disease. Many
      efforts have been made to identify poor prognostic factors that could be useful
      in selecting high-risk patients in 1st CR who may benefit from high-dose
      chemo/radiotherapy. However, the role of early transplantation in 1st CR remains
      unclear. We have retrospectively analyzed the results obtained with this
      procedure in 22 hospitals belonging to the Spanish GEL/TAMO cooperative group.
      Twenty-seven patients, of whom 19 were males, underwent autologous
      transplantation for Hodgkin's disease in 1st CR between January 1987 and January
      1996. Remission had been achieved after one (n = 22) or two (n = 5) lines of
      treatment. Twenty-four patients had advanced stage disease, 12 patients bulky
      mediastinal disease, nine bone marrow involvement and 18 had extranodal disease.
      Peripheral blood was used as the source of hematopoietic stem cells in 15
      patients, BM in nine, and both in three. All but three patients received
      chemotherapy-based conditioning regimens (16 CBV, four BEAM and four BEAC), while
      three were conditioned with CY and TBI. There were no transplant-related deaths.
      Median (range) times to recover >0.5 x 10(9)/l neutrophils and >50 x 10(9)/l
      platelets were 14 (8-56) days and 16 (8-240) days, respectively. With a median
      follow-up of 30 (8-66) months, 21 patients are alive and in continuous CR. Four
      patients who relapsed after transplant at 8, 17.5, 22 and 26 months achieved a
      second CR with conventional chemotherapy; one patient relapsed 92 months post
      transplant and died 5 months afterwards. Another patient died 30.5 months post
      transplant from a secondary malignancy. In conclusion, high-dose therapy in poor
      prognosis Hodgkin's disease in 1st CR was well tolerated with no transplant
      related mortalities. Although the follow-up of this series is relatively short,
      our results seem promising. Nevertheless, late relapses can occur, and the role
      of this procedure vs conventional treatment in very high-risk patients should be
      assessed in prospective randomized studies.

PMID- 9285543
TI  - Hepatitis B virus infection in allogeneic bone marrow transplantation.
AB  - Fourty-four patients who underwent allogeneic bone marrow transplantation
      (alloBMT) were studied for hepatitis B virus (HBV)-related complications. The
      mean follow-up period was 15.3 months. Positivity for HBV surface antigen (HBsAg)
      was observed in 10 patients (22.7%) throughout the study. Four of the 10 patients
      were HBsAg carriers before alloBMT, while the remaining six became HBsAg(+) after
      alloBMT. During the follow-up period (from 6 months to 45 months), an elevation
      in serum ALT activity was observed in the four carriers when immunosuppression
      was reduced or withdrawn. All of the four HBsAg carriers developed hepatitis, but
      none of them died of liver failure due to HBV. Only one death due to GVHD and
      diabetic ketoacidosis was observed in this group. Two of the four carriers
      received marrow from anti-HBs positive donors and one of them cleared HBsAg from
      his serum via adoptive immunity 8 months after transplantation. The remaining six
      patients acquired HBV after alloBMT, but we were unable to demonstrate the source
      of HBV. Five of them had a moderate increase in serum ALT activity while the
      other patient had a normal ALT. Two patients seroconverted to anti-HBs
      spontaneously. Two patients died during the follow-up, one due to intracranial
      hemorrhage and the other due to GVHD and accompanying pulmonary infection. The
      rest of the study group (34 patients) remained HBsAg(-) throughout the study. Two
      of them had an HBsAg(+) donor, but neither developed HBV infection in their
      follow-up period. The acquisition rate of HBV infection was relatively low in
      recipients who were positive for anti-HBs compared to those who were negative for
      anti-HBs (8 vs 19%). Anti-HBs positivity remained for a longer period in
      recipients who received marrow from anti-HBs positive donors compared to those
      recipients who had anti-HBs negative donors (median 12 vs 3 months). We think
      that HBV is a frequent cause of liver dysfunction in alloBMT patients where HBV
      infection is endemic. Whether the disease is in the form of reactivation of HBsAg
      positive recipients, or is acquired from unknown sources in recipients who never
      had contact with the virus, the course of the disease is not fatal. Silent
      serologic changes can be demonstrated if viral serologic markers are sought
      serially. Among them, the disappearance of serum anti-HBs may be important as it
      increases the risk of HBV contamination in recipients.

PMID- 9285544
TI  - Effects of non-major histocompatibility antigens on acute graft-versus-host
      reaction after allogeneic bone marrow transplantation.
AB  - In the present study using an experimental BMT system we analyzed the effects of
      disparity at non-MHC Ag including minor lymphocyte stimulatory-1a (Mls-1a) Ag on
      the acute GVH reaction (GVHR) induced by MHC class I Ag. Mismatch at MHC (class
      I) Ag alone did not induce clinically detectable acute GVHR in this model.
      However, BMT mice prepared with a combination of both class I and non-MHC Ag
      mismatches showed signs of clinical GVHR and various cytokines were produced by
      the spleen cells at an early stage (4 days) after BMT. Although no clinical GVHR
      was detected in BMT chimeras prepared with a non-MHC mismatched but MHC matched
      combination, large amounts of various cytokines were secreted by spleen cells.
      Cytokine production in the latter two kinds of chimeras paralleled the increase
      of Mls-1a reactive Vbeta6+ T cells in the host spleen. Marked cytokine production
      induced by Mls-1a Ag was confirmed by MLR. Thus, these cytokines appeared to be
      produced by T cells responding to Mls-1a (ie Vbeta6+ T cells) and to augment the
      T cell responses to MHC class I which resulted in clinically detectable GVHR in
      chimeras prepared with the combination mismatched at both MHC class I and non-MHC
      loci.

PMID- 9285545
TI  - Management of thrombotic microangiopathy following allogeneic transplantation:
      what is the role of plasma exchange?
AB  - Thrombotic microangiopathy (TMA) is an infrequent but serious complication of
      allogeneic transplantation. The success rate of plasma exchange (PE) reported in
      the treatment of this entity is a controversial subject. We report the outcome of
      10 patients with TMA post-allogeneic transplantation after treatment with PE. Two
      out of the 10 patients have not responded, five had a partial response, but died
      of acute GVHD or interstitial pneumonitis, and three have responded and
      recovered. Our study suggests that there are different degrees of TMA severity.
      Only mild multifactorial cases with no severe hemolysis (LDH activity <1000 U/l)
      may be fully resolved with PE.

PMID- 9285547
TI  - Th1 and Th2 cytokine responses after measles antigen stimulation in vitro in bone
      marrow transplant patients: response to measles vaccination.
AB  - In seronegative autologous bone marrow transplanted (ABMT) patients, a sustained
      cell-mediated immunity (CMI) has been shown to impair the antibody response after
      measles vaccination. To investigate if this might be caused by a preferential Th1
      cytokine response, interferon (IFN)-gamma and interleukin (IL)-10 production of
      peripheral blood mononuclear cells (PBMC) was analyzed after measles antigen (M
      ag) stimulation in vitro. The non-specific immune response was measured by IFN
      alpha, and IL-12 analyses. Fifty non-vaccinated patients following ABMT or
      allogeneic bone marrow transplantation (BMT) were included. IFN-gamma production
      was significantly higher in patients with a retained CMI to measles than in
      patients without (2.3 vs 0.8 IU/ml; P = 0.01). Only a non-significant tendency
      was seen in IL-10 production (48.6 vs 26.7 pg/ml; NS), whereas no difference was
      found in IFN-alpha or IL-12 production. A positive correlation between IFN-gamma
      and IL-10 production was found (r(s) = 0.49; P < 0.001). After vaccination of 14
      ABMT children, there was an increase in PBMC IFN-gamma production in vitro (2.5
      vs <0.1 IU/ml; P < 0.05), whereas no changes were seen in the IL-10, IFN-alpha,
      or antibody levels. These results suggest that both Th1 and Th2 cytokine
      production are increased by M-ag stimulation in patients with a retained CMI to
      measles, but the Th1 response seems to be stronger. The preferential Th1
      stimulation and increase in IFN-gamma production after vaccination may lead to a
      reduction in the humoral immune response which may explain the negative
      correlation between antibody production and T cell reactivity prior to
      vaccination.

PMID- 9285546
TI  - Quality of life in patients with acute myelogenous leukemia in prolonged first
      complete remission after bone marrow transplantation (allogeneic or autologous)
      or chemotherapy: a cross-sectional study of the EORTC-GIMEMA AML 8A trial.
AB  - A cross-sectional study of quality of life (QOL) was performed in 98 patients in
      continued first complete remission (CR) for 1-7.4 years, after inclusion in the
      AML 8A trial which prospectively compared allogeneic bone marrow transplantation
      (AlloBMT), autologous BMT (ABMT) and intensive consolidation chemotherapy.
      Several significant differences between the three treatment groups were observed,
      on the basis of patient self-reports, with regard to somatic symptoms (mouth
      sores, cough, hair loss, headache), repeated acute medical problems, physical
      functioning, role functioning, leisure activities and, above all, sexual
      functioning. There were also significant differences for overall physical
      condition, and overall quality of life. For all these parameters, the ranking was
      uniformly AlloBMT lower than ABMT lower than chemotherapy. These differences
      remain significant after adjustment for time interval between CR and QOL
      evaluation, sex or age. These results, confirming a higher risk of permanent
      impairment of QOL after BMT, may have an impact on medical decisions and warrant
      further studies.

PMID- 9285548
TI  - G-CSF mobilization of haemopoietic cell populations in SCID mice engrafted with
      human leukaemia.
AB  - We have studied granulocyte colony-stimulating factor (G-CSF)-induced
      mobilization of haemopoietic cells in severe combined immune-deficient (SCID)
      mice engrafted with human leukaemia. Three leukaemia cell lines were
      investigated: the HL60 myeloblastic cell line, a chronic myeloid leukaemia (CML)
      xenograft cell line and an acute myeloid leukaemia (AML) xenograft line.
      Engraftment was detected using immunofluorescent staining of class I human
      leukocyte antigens and flow cytometry. All the tumours grew as disseminated
      disease with engraftment of bone marrow preceding involvement of peripheral blood
      (PB). After treatment with G-CSF (250 microg/kg/day) for 5 days, mobilization of
      haemopoietic progenitor cells (HPCs) was observed in non-engrafted SCID mice (40
      fold) and in mice engrafted with human leukaemia (20-fold). G-CSF stimulated
      increases in PB HPCs and total numbers of host nucleated cells in leukaemia
      bearing mice but did not induce rises in numbers of circulating HL60 colony
      forming cells. Similarly, in mice engrafted with human CML or AML, G-CSF did not
      increase the number of malignant cells in the PB. These results provided evidence
      that the migration of normal and malignant haemopoietic cells into the PB are
      controlled by different mechanisms, and that contamination of PBSC harvests with
      leukaemic cells in SCID-human chimaeric mice is not enhanced by G-CSF-stimulated
      mobilization.

PMID- 9285549
TI  - Umbilical cord blood transplantation from unrelated donors in an adult weighing
      90 kilograms. Role of immunosuppression in engraftment.
AB  - A 40-year-old male weighing 90 kilograms was diagnosed with acute myeloblastic
      leukaemia M5a which was resistant to chemotherapy. Neither a related nor an
      unrelated HLA-compatible bone marrow donor could be found. A unit of cord blood
      was found with an HLA compatibility of four out of six loci, and was infused
      after conditioning with cyclophosphamide, total body irradiation and
      antilymphocyte globulin. The infused cord blood had 0.98 x 10(7) nucleated cells
      per kilogram. On day 35 after infusion the patient was considered to have graft
      failure. A second unit of cord blood was found, and after 3 days of
      antilymphocyte globulin, it was infused (day 41). The course was complicated by
      severe hypoxia and bilateral interstitial pulmonary infiltrates, and the patient
      was treated with high doses of methylprednisolone. On day 58 the leukocyte count
      increased to 3 x 10(9)/l, and there was total chimerism of the first cord blood
      unit infused. Two weeks later leukocyte counts decreased progressively and the
      patient died of a disseminated fungal infection. We discuss the importance of the
      number of nucleated cells per kilogram of body weight infused, and the role of
      intensive immunosuppression in engraftment of cord blood transplantations in
      adults.

PMID- 9285550
TI  - Unsuccessful CTL transfusion in a case of post-BMT Epstein-Barr virus-associated
      lymphoproliferative disorder (EBV-LPD).
AB  - A patient with AML (FAB M4Eo) developed EBV-LPD 1.5 months after allogeneic BMT
      from his one locus-mismatched mother, the diagnosis being confirmed on day +82.
      Attempts to eradicate the monoclonally proliferating LPD using chemotherapy
      (VP16/dexamethasone) followed by two doses of EBV-specific CTL and one dose of
      unstimulated donor leukocytes were not successful. We assume delay of infusions
      (day +100, +107) and insufficient CTL cell doses (total 9.2 x 10(6)) may have
      been responsible for the poor outcome in this case.

PMID- 9285551
TI  - Analysis of the immunoglobulin heavy-chain gene rearrangement providing molecular
      evidence of second lymphoma in a patient in apparent relapse after
      autotransplantation.
AB  - Development of a second lymphoma after autotransplantation is an unusual event.
      Its real incidence, however, could be underestimated, since histologic and
      immunophenotyping techniques are often unable to distinguish it from a relapse.
      We report a lymphoma patient in apparent relapse after 42 months of molecular
      remission achieved by autotransplantation. Sequencing analysis of the
      immunoglobulin heavy-chain genes showed that the rearrangement of variable,
      diversity and joining segments had changed between diagnosis and relapse and
      suggested that a second lymphoma had developed.

PMID- 9285552
TI  - Local administration of platelets.

PMID- 9285553
TI  - Peripheral blood progenitor cell collections in children with low platelet counts
      are safe.

PMID- 9285554
TI  - Mdm2: keeping p53 under control.
AB  - The Mdm2 gene is overexpressed in several human tumors. The oncogenic potential
      of Mdm2 is partially explained by the inhibition of the activity of the tumor
      suppressor protein p53. Determination of the three-dimensional structure of
      complexes between Mdm2 and the N-terminal p53 peptide provided a molecular basis
      for the inhibition of the transcriptional function of p53 by Mdm2. More
      dramatically, p53 is targeted by Mdm2 for rapid degradation. The Mdm2 gene itself
      is activated by p53, which gives the opportunity for feed-back control of p53
      activity. Keeping p53 under control is most likely the major task of Mdm2 during
      early development. Recently, evidence was provided for an alternative, p53
      independent function of Mdm2.

PMID- 9285555
TI  - Linking Myb to the cell cycle: cyclin-dependent phosphorylation and regulation of
      A-Myb activity.
AB  - A-myb, a conserved member of the Myb proto-oncogene family, encodes a sequence
      specific DNA binding protein (A-Myb) that binds to and transactivates promoters
      containing myb-binding sites. Previous work has suggested that the C-terminus of
      A-Myb functions as a regulatory domain, however, the physiological signals that
      control the activity of A-Myb have not yet been identified. The presence of
      potential phosphorylation sites for cyclin-dependent kinases in the C-terminus of
      A-Myb has prompted us to examine the possibility that the function of A-Myb is
      controlled by the cell cycle. We here show that the transactivation potential of
      A-Myb is repressed by the C-terminal domain and that phosphorylation of A-Myb,
      induced by cyclins A and E, relieves this inhibitory effect. Our work provides
      the first evidence that the function of A-Myb is regulated by the cell cycle
      machinery and that the carboxy-terminal domain of A-Myb acts as a cell cycle
      sensor. In addition, we show that A-myb mRNA expression is also cell cycle
      regulated and attains maximal levels during the late G1- and early S-phase. Thus,
      A-Myb appears to be controlled by two different mechanisms resulting in maximal A
      Myb activity during the G1/S-transition and the S-phase of the cell cycle.

PMID- 9285556
TI  - Mutations of critical amino acids affect the biological and biochemical
      properties of oncogenic A-Raf and Raf-1.
AB  - The catalytic domains of the Raf family of protein kinases (deltaRaf) differ in
      their ability to activate MEK in vitro and in vivo and in their ability to
      oncogenically transform mammalian cells. The kinase domain of B-Raf is more
      active than the equivalent portion of Raf-1 which in turn is more active than A
      Raf. In Raf-1 the phosphorylation or mutation to aspartic acid of two key
      tyrosine residues upstream of the ATP binding site has been demonstrated to
      significantly potentiate catalytic activity. In A-Raf the analogous amino acids
      are also tyrosine whereas in B-Raf they are aspartic acid. To determine if these
      differences in amino acid sequence influence the relative catalytic activity of
      the Raf kinase domains we constructed forms of deltaA-Raf, deltaB-Raf and
      deltaRaf-1 that encode either aspartic acid [DD], phenylalanine [FF] or tyrosine
      [YY] at these positions. These proteins were expressed both in mammalian cells as
      fusions with the hormone binding domain of the estrogen receptor and as epitope
      tagged proteins in Sf9 insect cells to test their oncogenic and catalytic
      potentials. When expressed in Rat1 or 3T3 cells in the presence of hormone all of
      the deltaRaf-1:ER and deltaA-Raf:ER proteins were transforming with the exception
      of the [FF] form of deltaA-Raf. In general the [DD] forms of the deltaRaf-1:ER
      and deltaA-Raf:ER proteins were the most potently oncogenic which correlated with
      their ability to elicit activation of the MAP kinase pathway. Consistent with the
      transformation data, the catalytic activity of the [DD] forms of deltaA-Raf:ER
      and deltaRaf-1:ER was about ten times greater than the cognate [FF] and [YY]
      forms of the proteins. By contrast all of the deltaB-Raf:ER proteins were highly
      transforming and deltaB-Raf catalytic activity was largely unaffected by mutation
      of the aforementioned aspartic acids to either tyrosine or phenylalanine. Similar
      results were obtained with epitope-tagged forms of deltaA-Raf, deltaB-Raf and
      deltaRaf-1 expressed in Sf9 cells. These data provide support for the model that
      key tyrosine residues in the protein kinase domains of A-Raf and Raf-1 are
      important in the regulation of catalytic activity. In addition they demonstrate
      that the higher intrinsic activity of B-Raf cannot be explained simply by the
      presence of aspartic acids at the analogous positions.

PMID- 9285557
TI  - Defective induction but normal activation and function of p53 in mouse cells
      lacking poly-ADP-ribose polymerase.
AB  - Poly-ADP-ribose polymerase (PARP) and p53 are both induced by DNA damage and each
      has been proposed to mediate the normal cellular response to damage. We find that
      embryo fibroblasts from PARP-null mice have a approximately twofold lower basal
      level of p53 and that the induction of p53 in response to DNA damage or
      nucleotide depletion is more than twofold less than in normal mouse cells. These
      factors combine to decrease the induced level of the p53 protein in PARP
      deficient cells by 4-5-fold, compared to normal cells. However, there is
      virtually no decrease in the induction of p53 activity in PARP-deficient cells,
      as assayed with a p53-responsive promoter. Furthermore, cells lacking PARP arrest
      normally in G1 after DNA damage, in contrast to cells lacking p53, where this
      checkpoint is absent. Other p53-dependent properties, such as the mitotic spindle
      checkpoint and permissivity for gene amplification, are also normal in PARP
      deficient cells. We conclude that the induced level of the p53 protein is
      governed by a combination of PARP-dependent and PARP-independent pathways and
      that the activation of p53 is largely PARP-independent. The results are
      consistent with a model in which the regulation of gene expression by p53
      involves both increases in the amount of the protein and activation of p53 as a
      transcription factor.

PMID- 9285558
TI  - Association of Krev-1/rap1a with Krit1, a novel ankyrin repeat-containing protein
      encoded by a gene mapping to 7q21-22.
AB  - Krev-1/rap1A is an evolutionarily conserved Ras-family GTPase whose cellular
      function remains unclear, but which has been proposed to function as a tumor
      suppressor gene, and may act as a Ras antagonist. To elucidate Krev-1 activity,
      we have used LexA-Krev-1 in a two-hybrid screen of a HeLa cell cDNA library. Of
      the two cDNA classes isolated, one contained a single isolate encoding the known
      Krev-1 interactor Raf, while the second contained multiple isolates coding for a
      previously undescribed protein which we have designated Kritl (for Krev
      Interaction Trapped 1). The full length Krit1 cDNA encodes a protein of 529 amino
      acids, with an amino-terminal ankyrin repeat domain and a novel carboxy-terminal
      domain required for association with Krit1. Krit1 interacted strongly with Krev-1
      but only weakly with Ras, suggesting it might specifically regulate Krev-1
      activities. Krit1 mRNA and protein are expressed endogenously at low levels, with
      tissue specific variation. Intriguingly, the Krit cDNA has been mapped by FISH to
      chromosome 7q21-22, a region known to be frequently deleted or amplified in
      multiple forms of cancer.

PMID- 9285559
TI  - Integration of proviral DNA into the PDGF beta-receptor gene in HTLV-I-infected T
      cells results in a novel tyrosine kinase product with transforming activity.
AB  - We have previously shown that noninfected human T-cell lines express the
      canonical 5.7 kb mRNA coding for the type beta platelet-derived growth factor
      receptor (PDGF beta-receptor), whereas HTLV-I-infected T-cell lines express a
      novel PDGF beta-receptor mRNA of 3.8 kb. In this report, we have extended those
      studies to molecularly characterize the 3.8 kb PDGF beta-receptor mRNA and show
      that it has resulted from integration of an apparently undeleted HTLV-I provirus
      into the PDGF beta-receptor gene in an orientation enabling expression of a
      truncated PDGF beta-receptor mRNA using the 3' HTLV-I long terminal repeat as a
      promoter. Further, NIH3T3 cells transfected with a plasmid containing the
      truncated PDGF beta-receptor ORF plasmid generate colonies in soft agar with more
      cells per colony than untransfected cells, or cells transfected with the Tax 1 or
      PDGF-B (c-sis) plasmids. These results indicate that the truncated PDGF beta
      receptor protein acquires transforming capability and that HTLV-I-induced
      truncation of PDGF beta-receptor may correlate with HTLV-I-associated neoplasia
      of human T-cells.

PMID- 9285560
TI  - Molecular pathology in basal cell cancer with p53 as a genetic marker.
AB  - Human basal cell cancer (BCC) has unique growth characteristics with virtual
      inability to metastasize. We investigated clonality and genetic progression using
      p53 mutations as marker. Sampling was done through microdissection of frozen
      immunohistochemically stained 16 microm slices of tumors. From 11 BCC tumors 78
      samples were analysed. Direct DNA sequencing of exons 5-8 was performed,
      haplotypes were determined after cloning of p53 exons and loss of heterozygosity
      (LOH) ascertained by microsatellite analysis. All tumors had p53 mutations and in
      a majority both p53 alleles were affected, commonly through missense mutations.
      Microdissection of small parts (50-100 cells) of individual tumors showed BCC to
      be composed of a dominant cell clone and prone to genetic progression with
      appearance of subclones with a second and even third p53 mutation. Samples from
      normal immunohistochemically negative epidermis always showed wild type sequence,
      except for a case of previously unknown germline p53 mutation. Our analysis also
      included p53 immunoreactive patches i.e. morphologically normal epidermis with a
      compact pattern of p53 immunoreactivity. Mutations within those were never the
      same as in the adjacent BCC. This detailed study of only one gene thus uncovered
      a remarkable heterogeneity within a tumor category famous for its benign clinical
      behavior.

PMID- 9285562
TI  - SAGE transcript profiles for p53-dependent growth regulation.
AB  - Serial analysis of gene expression (SAGE) allows for a quantitative,
      representative, and comprehensive profile of gene expression. We have utilized
      SAGE technology to contrast the differential gene expression profile in rat
      embryo fibroblast cells producing temperature-sensitive p53 tumor suppressor
      protein at permissive or non-permissive temperatures. Analysis of approximately
      15,000 genes revealed that the expression of 14 genes (P < 0.001, > or = 0.03%
      abundance) was dependent on functional p53 protein, whereas the expression of
      three genes was significantly higher in cells producing non-functional p53
      protein. Those genes whose expression was increased by functional p53 include
      RAS, U6 snRNA, cyclin G, EGR-1, and several novel genes. The expression of actin,
      tubulin, and HSP70 genes was elevated at the non-permissive temperature for p53
      function. Interestingly, the expression of several genes was dependent on a non
      temperature-sensitive mutant p53 suggesting altered transcription profiles
      dependent on specific p53 mutant proteins. These results demonstrate the utility
      of SAGE for rapidly and reproducibly evaluating global transcriptional responses
      within different cell populations.

PMID- 9285561
TI  - Induction of apoptosis in Mv1Lu cells by expression of competitive RB1 mutants.
AB  - The Retinoblastoma tumor suppressor gene (RB1) plays a role in a variety of human
      cancers. Experimental analyses have indicated that the protein product of the RB1
      gene (pRb) plays a role in cell cycle regulation. pRb function is dependent on
      its ability to bind to cellular factors, which is facilitated by multiple protein
      binding domains within pRb. Mutations within these domains which eliminate the
      ability of pRb to bind its targets result in loss of function. Although loss of
      pRb function may lead to uncontrolled cellular proliferation, tumorigenesis is
      not the only response to pRb inactivation. Examination of various tissues from
      RB1-nullizygous mouse embryos showed problems in differentiation and induction of
      apoptosis, suggesting that the ultimate response to the loss of pRb is influenced
      by cellular context. It has previously been demonstrated in RB1-negative Saos-2
      cells that co-expression of the C-terminal domain of pRb with wildtype pRb
      resulted in escape from G1 arrest and continued cell cycling. In this paper we
      demonstrate that in RB1-positive Mv1Lu cells, expression of the A/B pocket region
      or the N-terminus (when combined with a nuclear localization signal), but not the
      C-terminal domain, is able to competitively disrupt the function of the
      endogenous pRb, and that the result of this disruption is apoptosis.

PMID- 9285563
TI  - Elevated expression of eIF4E and FGF-2 isoforms during vascularization of breast
      carcinomas.
AB  - The translation initiation factor eIF4E is a novel protooncogene found over
      expressed in most breast carcinomas (Kerekatte et al., 1995), but the pathology
      where this elevation is initially manifested and its possible role in cancer
      progression are unknown. We report that eIF4E is markedly increased in
      vascularized malignant ductules of invasive carcinomas, whereas necrotic and
      avascular ductal carcinomas in situ display significantly lower levels. eIF4E
      facilitates the synthesis of FGF-2, a powerful tumor angiogenic factor.
      Conversely, reducing eIF4E with antisense RNA in MDA-435 cells suppresses their
      tumorigenic and angiogenic properties, consistent with loss of FGF-2 synthesis.
      These findings suggest a causal role for eIF4E in tumor vascularization.

PMID- 9285564
TI  - Identification of an additional p53-responsive site in the human epidermal growth
      factor receptor gene promotor.
AB  - Exogenously introduced wild-type and mutant p53 have recently been reported to
      enhance the human epidermal growth factor receptor (EGF-R) gene promoter activity
      in p53-deficient Saos2 osteosarcoma cells. A p53 binding site residing at
      position -265/-239 in the EGF-R proximal promoter has also been identified. We
      investigated the p53 regulation of EGF-R core promoter activity in human cell
      lines with varying endogenour p53 status. Wild-type and mutant p53Ala143 enhanced
      the EGF-R core promotor activity in cells that were either p53-deficient or
      contained wild-type or mutant endogenous p53. Upon further characterization of
      the various deletion fragments of the EGF-R promoter, we identified a wild-type
      p53 responsive 62 bp region residing at position -167/-105. The -167/-105 segment
      was responsive only to wild-type p53 but not to mutant p53Ala143 or p53His273.
      The -167/-105 segment of the EGF-R promotor contains one perfect and several
      imperfect consensus p53-binding half sites; indeed in gel shift experiments the
      62 bp -167/-105 segment as well as the oligonucleotides corresponding to two p53
      consensus half-sites within the 62 bp fragment, exhibited binding to p53
      containing protein complexes. Thus, we have identified an additional wild-type
      p53 responsive site in the human EGF-R promoter. This site containing consensus
      p53-binding sequences resides at position -167/-105 and is proximal to recently
      identified p53 binding element located at position -265/-239 in the EGF-R
      promotor.

PMID- 9285566
TI  - Comparative mutational analysis of DPC4 (Smad4) in prostatic and colorectal
      carcinomas.
AB  - Allelic deletions of chromosome 18q are reported to be common in prostate and
      colorectal cancers, suggesting that one or more tumor suppressor genes on 18q are
      involved in the genesis of these neoplasms. The DPC4 gene, a recently identified
      candidate tumor suppressor in 18q21, was examined for evidence of inactivation in
      prostatic carcinomas, and results compared to those of a parallel analysis of
      colorectal carcinomas, for which DPC4 mutation has been reported in approximately
      10% of cases. In this study, only three (10%) of 29 informative primary prostate
      cancers showed allelic loss of chromosome 18q21 markers, and no point mutations
      or deletions of DPC4 were detected in the complete set of 45 primary or
      metastatic cases. In contrast, five (56%) of nine primary colorectal tumors
      displayed allelic loss of 18q markers and in one of these a somatically acquired
      G-->T missense mutation was found in exon 1. Of twelve colorectal tumor cell
      lines, one showed a G-->C missense mutation in exon 8 and two had partial
      homozygous deletions that would likely abrogate gene function. These data suggest
      that DPC4 is rarely if ever mutated during prostatic oncogenesis, whereas
      inactivation of this gene may contribute to the genesis of a subset of colorectal
      carcinomas.

PMID- 9285565
TI  - Cellular and viral trans-acting factors modulate N-myc2 promoter activity in
      woodchuck liver tumors.
AB  - Activation of the N-myc2 oncogene by integration of woodchuck hepatitis virus
      (WHV) DNA is a central event in woodchuck liver oncogenesis. In this study, we
      have evaluated the influence of several cellular and viral trans-acting factors
      and mediators of inflammation on N-myc2 promoter activity in hepatoma cell lines.
      Ets oncoproteins, including Ets1, Ets2 and PEA3 efficiently activated a chimeric
      N-myc2 promoter/luciferase reporter gene. By electrophoretic mobility shift
      assays, we show that Etsl and Ets2 proteins can efficiently bind two consensus
      Ets sites located within a 59 bp sequence upstream of the N-myc2 transcription
      start site. Site-directed mutagenesis of these Ets-binding motifs abolished
      transactivation of the N-myc2 promoter by Ets proteins. Addition of interleukin-6
      (IL-6) induced a weak but reproducible activation of the N-myc2 promoter, while
      IL-1 was ineffective. We further show that the N-myc2 promoter can be
      transactivated by the hepadna-virus X protein, and that distal promoter sequences
      are required for both IL-6 and X responsiveness. Similar effects of these factors
      were observed in the context of the N-myc2 promoter activated by WHV cis
      regulatory elements. In view of the high-level expression of the N-myc2 oncogene
      in most woodchuck liver tumors, the Ets oncoproteins, inflammation-associated
      cytokine IL-6 and the viral X transactivator might play important roles in
      hepadnavirus-associated tumorigenesis.

PMID- 9285568
TI  - Malaria initiative needs drug industry's backing.

PMID- 9285567
TI  - Keratinocyte growth factor expression in hormone insensitive prostate cancer.
AB  - Cellular interactions between stroma and epithelium are important in the growth
      and proliferation of prostate cancer. Peptide growth factors may facilitate the
      progression of prostate cancer as autocrine and/or paracrine factors.
      Keratinocyte Growth Factor (KGF or FGF7) has a differentiative and proliferative
      effect on the epithelium of the developing rat prostate. We investigated if KGF
      may act as a paracrine agent in human prostate cancer and examined the expression
      of KGF and Fibroblast Growth Factor Receptors (FGFRs) (IIIb and IIIc isoforms of
      the FGFR1 and FGFR2 genes). Sixty-five percent (11 out of 17 informative cases)
      of prostate cancers (CaP) expressed KGF mRNA by RT-PCR, while KGF expression was
      not detected in benign prostatic hyperplasia (BPH) (n = 6). Upregulation of KGF
      expression was related to hormone insensitive tumours (P<0.05). Tumour grade and
      stage were not associated with KGF expression. The source of KGF expression was
      further characterised using an in vitro primary culture model, showing its
      restriction to the prostatic stroma. The FGFR1IIIb isoform was expressed in all
      cases of prostate cancer (n = 17), and FGFR1IIIc mRNA was not detected. In the
      BPH group, FGFR1IIIb transcripts were detected in four out of six cases.
      FGFR2IIIb expression was detected in five of six cases of BPH and twelve out of
      seventeen (71%) cases of prostate cancer. In CaP, though not reaching statistical
      significance, the persistence of FGFR2IIIb expression appeared to be associated
      with hormone insensitive tumours (P=0.052). FGFR2IIIc expression was present in
      eleven of seventeen tumours but was absent in all six cases of BPH. Functional
      assessment of recombinant KGF in a proliferation assay demonstrated a mitogenic
      effect of up to 100% on cultured prostatic epithelial cells.

PMID- 9285569
TI  - Funding assured for international malaria sequencing project.

PMID- 9285571
TI  - 'Action needed to counter bioterrorism'.

PMID- 9285570
TI  - $100m payout after drug data withheld.

PMID- 9285572
TI  - Miami AIDS researcher denies charges over billing irregularities.

PMID- 9285574
TI  - Wisdom in physiology.

PMID- 9285573
TI  - Public-sector patents on human DNA.

PMID- 9285575
TI  - Apoptosis. CED-4 is a stranger no more.

PMID- 9285576
TI  - Neurodegeneration. A silent channel opens its gates.

PMID- 9285578
TI  - Death and the demon drink in Russia.

PMID- 9285577
TI  - Protein folding. Folding with a two-stroke motor.

PMID- 9285579
TI  - Immunology. Inside the gearbox of the dendritic cell.

PMID- 9285580
TI  - John Zachary Young (1907-97)

PMID- 9285581
TI  - Hyperactive antifreeze protein from beetles.

PMID- 9285582
TI  - Role of CED-4 in the activation of CED-3.

PMID- 9285583
TI  - Vaccination onto bare skin.

PMID- 9285584
TI  - Seeing where your hands are.

PMID- 9285585
TI  - The crystal structure of the asymmetric GroEL-GroES-(ADP)7 chaperonin complex.
AB  - Chaperonins assist protein folding with the consumption of ATP. They exist as
      multi-subunit protein assemblies comprising rings of subunits stacked back to
      back. In Escherichia coli, asymmetric intermediates of GroEL are formed with the
      co-chaperonin GroES and nucleotides bound only to one of the seven-subunit rings
      (the cis ring) and not to the opposing ring (the trans ring). The structure of
      the GroEL-GroES-(ADP)7 complex reveals how large en bloc movements of the cis
      ring's intermediate and apical domains enable bound GroES to stabilize a folding
      chamber with ADP confined to the cis ring. Elevation and twist of the apical
      domains double the volume of the central cavity and bury hydrophobic peptide
      binding residues in the interface with GroES, as well as between GroEL subunits,
      leaving a hydrophilic cavity lining that is conducive to protein folding. An
      inward tilt of the cis equatorial domain causes an outward tilt in the trans ring
      that opposes the binding of a second GroES. When combined with new functional
      results, this negative allosteric mechanism suggests a model for an ATP-driven
      folding cycle that requires a double toroid.

PMID- 9285586
TI  - Enantioseparation using apoenzymes immobilized in a porous polymeric membrane.
AB  - Chemical separations represent a large portion of the cost of bringing any new
      pharmaceutical product to the market. Membrane-based separation technologies, in
      which the target molecule is selectively extracted and transported across a
      membrane, are potentially more economical and easier to implement than competing
      separations methods; but membranes with higher transport selectivities are
      required. Here we describe an approach for preparing highly selective membranes
      which involves immobilizing apoenzymes within a microporous composite. The
      apoenzyme selectively recognizes its substrate molecule and transports it across
      the composite membrane, without effecting the unwanted chemical conversion of the
      substrate molecule to product. We demonstrate this approach using three different
      apoenzymes. Most importantly, it can be used to make enantioselective membranes
      for chiral separations, one of the most challenging and important problems in
      bioseparations technology. We are able to achieve a fivefold difference between
      the transport rates of D- and L-amino acids.

PMID- 9285587
TI  - Genetic tagging of humpback whales.
AB  - The ability to recognize individual animals has substantially increased our
      knowledge of the biology and behaviour of many taxa. However, not all species
      lend themselves to this approach, either because of insufficient phenotypic
      variation or because tag attachment is not feasible. The use of genetic markers
      ('tags') represents a viable alternative to traditional methods of individual
      recognition, as they are permanent and exist in all individuals. We tested the
      use of genetic markers as the primary means of identifying individuals in a study
      of humpback whales in the North Atlantic Ocean. Analysis of six microsatellite
      loci among 3,060 skin samples collected throughout this ocean allowed the
      unequivocal identification of individuals. Analysis of 692 'recaptures',
      identified by their genotype, revealed individual local and migratory movements
      of up to 10,000 km, limited exchange among summer feeding grounds, and mixing in
      winter breeding areas, and also allowed the first estimates of animal abundance
      based solely on genotypic data. Our study demonstrates that genetic tagging is
      not only feasible, but generates data (for example, on sex) that can be valuable
      when interpreting the results of tagging experiments.

PMID- 9285588
TI  - Neurodegeneration in Lurcher mice caused by mutation in delta2 glutamate receptor
      gene.
AB  - Lurcher (Lc) is a spontaneous, semidominant mouse neurological mutation.
      Heterozygous Lurcher mice (Lc/+) display ataxia as a result of a selective, cell
      autonomous and apoptotic death of cerebellar Purkinje cells during postnatal
      development. Homozygous Lurcher mice (Lc/Lc) die shortly after birth because of a
      massive loss of mid- and hindbrain neurons during late embryogenesis. We have
      used positional cloning to identify the mutations responsible for
      neurodegeneration in two independent Lc alleles as G-to-A transitions that change
      a highly conserved alanine to a threonine residue in transmembrane domain III of
      the mouse delta2 glutamate receptor gene (GluR delta2). Lc/+ Purkinje cells have
      a very high membrane conductance and a depolarized resting potential, indicating
      the presence of a large, constitutive inward current. Expression of the mutant
      GluR delta2(Lc) protein in Xenopus oocytes confirmed these results, demonstrating
      that Lc is inherited as a neurodegenerative disorder resulting from a gain-of
      function mutation in a glutamate receptor gene. Thus the activation of apoptotic
      neuronal death in Lurcher mice may provide a physiologically relevant model for
      excitotoxic cell death.

PMID- 9285589
TI  - A second endogenous cannabinoid that modulates long-term potentiation.
AB  - Cannabinoid receptors are molecular targets for marijuana and hashish, the
      widespread drugs of abuse. These receptors are expressed in areas of the central
      nervous system that contribute in important ways to the control of memory,
      cognition, movement and pain perception. Indeed, such functions can be strongly
      influenced by cannabinoid drugs, with consequences that include euphoria,
      analgesia, sedation and memory impairment. Although the pharmacology of
      cannabinoid drugs is now beginning to be understood, we still lack essential
      information on the endogenous signalling system(s) by which cannabinoid receptors
      are normally engaged. An endogenous ligand for cannabinoid receptors, anandamide,
      has been described. Here we report that sn-2 arachidonylglycerol (2-AG), a
      cannabinoid ligand isolated from intestinal tissue, is present in brain in
      amounts 170 times greater than anandamide. 2-AG is produced in hippocampal slices
      by stimulation of the Schaffer collaterals, an excitatory fibre tract that
      projects from CA3 to CA1 neurons. Formation of 2-AG is calcium dependent and is
      mediated by the enzymes phospholipase C and diacylglycerol lipase. 2-AG activates
      neuronal cannabinoid receptors as a full agonist, and prevents the induction of
      long-term potentiation at CA3-CA1 synapses. Our results indicate that 2-AG is a
      second endogenous cannabinoid ligand in the central nervous system.

PMID- 9285590
TI  - Placental abnormalities in mouse embryos lacking the orphan nuclear receptor ERR
      beta.
AB  - Classical endocrine studies have shown that steroid hormones are required for the
      maintenance of pregnancy and placental viability. The oestrogen-receptor-related
      receptor beta (ERR-beta) is an orphan member of the superfamily of nuclear
      hormone receptors. Although ERR-beta is homologous to the oestrogen receptor and
      binds the oestrogen response element, it is not activated by oestrogens.
      Expression of ERR-beta during embryogenesis defines a subset of extra-embryonic
      ectoderm that subsequently forms the dome of the chorion, suggesting that ERR
      beta may be involved in early placental development. Homozygous mutant embryos
      generated by targeted disruption of the Estrrb gene have severely impaired
      placental formation, and die at 10.5 days post-coitum. The mutants display
      abnormal chorion development associated with an overabundance of trophoblast
      giant cells and a severe deficiency of diploid trophoblast. The phenotype can be
      rescued by aggregation of Estrrb mutant embryos with tetraploid wild-type cells,
      which contribute exclusively to extra-embryonic tissues. Our results indicate
      that ERR-beta has an important role in early placentation, and suggest that an
      inductive signal originating from or modified by the chorion is required for
      normal trophoblast proliferation and differentiation.

PMID- 9285591
TI  - Inflammatory stimuli induce accumulation of MHC class II complexes on dendritic
      cells.
AB  - Dendritic cells have the remarkable property of presenting any incoming antigen.
      To do so they must not only capture antigens with high efficiency and broad
      specificity, but must also maximize their capacity to load class II molecules of
      the major histocompatibility complex (MHC) with antigenic peptides in order to
      present a large array of epitopes from different proteins, each at a sufficient
      copy number. Here we show that formation of peptide-MHC class II complexes is
      boosted by inflammatory stimuli that induce maturation of dendritic cells. In
      immature dendritic cells, class II molecules are rapidly internalized and
      recycled, turning over with a half-life of about 10 hours. Inflammatory stimuli
      induce a rapid and transient boost of class II synthesis, while the half-life of
      class II molecules increases to over 100 hours. These coordinated changes result
      in the rapid accumulation of a large number of long-lived peptide-loaded MHC
      class II molecules capable of stimulating T cells even after several days. The
      capacity of dendritic cells to load many antigenic peptides over a short period
      of initial exposure to inflammatory stimuli could favour presentation of
      infectious antigens.

PMID- 9285592
TI  - Developmental regulation of MHC class II transport in mouse dendritic cells.
AB  - Dendritic cells (DCs) have the unique capacity to initiate primary and secondary
      immune responses. They acquire antigens in peripheral tissues and migrate to
      lymphoid organs where they present processed peptides to T cells. DCs must
      therefore exist in distinct functional states, an idea that is supported by
      observations that they downregulate endocytosis and upregulate surface molecules
      of the class II major histocompatibility complex (MHC) upon maturation. Here we
      investigate the features of DC maturation by reconstituting the terminal
      differentiation of mouse DCs in vitro and in situ. We find that early DCs,
      corresponding to those found in peripheral tissues, exhibit a phenotype in which
      most class II molecules are intracellular and localized to lysosomes. Upon
      maturation, these cells give rise to a new intermediate phenotype in which
      intracellular class II molecules are found in peripheral non-lysosomal vesicles,
      similar to the specialized CIIV population seen in B cells. The intermediate
      cells then differentiate into late DCs which express almost all of their class II
      molecules on the plasma membrane. These variations in class II
      compartmentalization are accompanied by dramatic alterations in the intracellular
      transport of the new class II molecules and in antigen presentation. We found
      that although early DCs could not present antigen immediately after uptake,
      efficient presentation of the previously internalized antigen occurred after
      maturation, 24-48 hours later. By regulating class II transport and
      compartmentalization, DCs are able to delay antigen display, a property crucial
      to their role in immune surveillance.

PMID- 9285593
TI  - Distinct actions of cis and trans ATP within the double ring of the chaperonin
      GroEL.
AB  - The chaperonin GroEL is a double-ring structure with a central cavity in each
      ring that provides an environment for the efficient folding of proteins when
      capped by the co-chaperone GroES in the presence of adenine nucleotides.
      Productive folding of the substrate rhodanese has been observed in cis ternary
      complexes, where GroES and polypeptide are bound to the same ring, formed with
      either ATP, ADP or non-hydrolysable ATP analogues, suggesting that the specific
      requirement for ATP is confined to an action in the trans ring that evicts GroES
      and polypeptide from the cis side. We show here, however, that for the folding of
      malate dehydrogenase and Rubisco there is also an absolute requirement for ATP in
      the cis ring, as ADP and AMP-PNP are unable to promote folding. We investigated
      the specific roles of binding and hydrolysis of ATP in the cis and trans rings
      using mutant forms of GroEL that bind ATP but are defective in its hydrolysis.
      Binding of ATP and GroES in cis initiated productive folding inside a highly
      stable GroEL-ATP-GroES complex. To discharge GroES and polypeptide, ATP
      hydrolysis in the cis ring was required to form a GroEL-ADP-GroES complex with
      decreased stability, priming the cis complex for release by ATP binding (without
      hydrolysis) in the trans ring. These observations offer an explanation of why
      GroEL functions as a double-ring complex.

PMID- 9285594
TI  - DNA renaturation activity of the SMC complex implicated in chromosome
      condensation.
AB  - Chromosome condensation occurs in mitosis before the separation of sister
      chromatids, and requires DNA topoisomerase II and a group of proteins called
      SMCs. The resulting condensed chromosomes in metaphase have a complex
      hierarchical structure. SMCs, the components of condensed chromosomes, are also
      required for the separation of sister chromatids and gene dosage compensation,
      and are found in a range of organisms from yeasts to mammals. However, the
      mechanisms by which the SMCs contribute to chromosome condensation are unknown.
      We have studied chromosomes in fission-yeast SMC mutants cut3-477 and cut14-208,
      which remain largely non-condensed during mitosis at the restrictive temperature
      (36 degrees C). To test their role in DNA condensation, we isolated the proteins
      Cut3 and Cut14 as an oligomeric complex, and tested their interactions with
      isolated DNA. The complex efficiently promoted the DNA renaturation reactions
      (the winding up of single-strand DNAs into double helical DNA) as much as
      approximately 70-fold more efficiently than RecA, which is a bacterial protein
      with similar activity. The activity of the mutant complex was heat sensitive. As
      DNA winding by renaturation is a potential cause of supercoiling, the SMC complex
      may be implicated in promoting the higher-order DNA coiling found in condensed
      chromosomes.

PMID- 9285595
TI  - Metal ion catalysis during splicing of premessenger RNA.
AB  - The removal of intervening sequences from premessenger RNA is essential for the
      expression of most eukaryotic genes. The spliceosome ribonucleoprotein complex
      catalyses intron removal by two sequential phosphotransesterification reactions,
      but the catalytic mechanisms are unknown. It has been proposed that two divalent
      metal ions may mediate catalysis of both reaction steps, activating the 2'- or 3'
      hydroxyl groups for nucleophilic attack and stabilizing the 3'-oxyanion leaving
      groups by direct coordination. Here we show that in splicing reactions with a
      precursor RNA containing a 3'-sulphur substitution at the 5' splice site,
      interaction between metal ion and leaving group is essential for catalysis of the
      first reaction step. This establishes that the spliceosome is a metalloenzyme and
      demonstrates a direct parallel with the catalytic strategy used by the self
      splicing group I intron from Tetrahymena. In contrast, 3'-sulphur substitution at
      the 3' splice site provides no evidence for a metal ion-leaving group interaction
      in the second reaction step, suggesting that the two steps of splicing proceed by
      different catalytic mechanisms and therefore in distinct active sites.

PMID- 9285596
TI  - A second catalytic metal ion in group I ribozyme.
AB  - Although only a subset of protein enzymes depend on the presence of a metal ion
      for their catalytic function, all naturally occurring RNA enzymes require metal
      ions to stabilize their structure and for catalytic competence. In the self
      splicing group I intron from Tetrahymena thermophila, several divalent metals can
      serve structural roles, but only Mg2+ and Mn2+ promote splice-site cleavage and
      exon ligation. A study of a ribozyme reaction analogous to 5'-splice-site
      cleavage by guanosine uncovered the first metal ion with a definitive role in
      catalysis. Substitution of the 3'-oxygen of the leaving group with sulphur
      resulted in a metal-specificity switch, indicating an interaction between the
      leaving group and the metal ion. Here we use 3'-(thioinosylyl)-(3'-->5')-uridine,
      IspU, as a substrate in a reaction that emulates exon ligation. Activity requires
      the addition of a thiophilic metal ion (Cd2+ or Mn2+), providing evidence for
      stabilization of the leaving group by a metal ion in that step of splicing. Based
      on the principle of microscopic reversibility, this metal ion activates the
      nucleophilic 3'-hydroxyl of guanosine in the first step of splicing, supporting
      the model of a two-metal-ion active site.

PMID- 9285597
TI  - Selective excision of adenomas originating in or extending into the pituitary
      stalk with preservation of pituitary function.
AB  - When the surgeon identifies an adenoma within the gland and selectively excises
      it, endocrine-active pituitary tumors are usually cured and pituitary function is
      preserved. Occasionally ectopic adenomas arise primarily in the pituitary stalk
      or arise superiorly in the midportion of the anterior lobe and extend upward
      within the stalk. To determine if these tumors can be selectively excised with
      preservation of pituitary function, the authors examined the outcome of selective
      adenomectomy in 10 patients with Cushing's disease with an ectopic adenoma
      originating in, and confined to, the stalk (four microadenomas) or an adenoma
      extending superiorly through the diaphragma sella and into the stalk (five
      microadenomas and one macroadenoma) from an operative series of 516 patients with
      Cushing's disease. To reach the adenoma transsphenoidally in these patients, the
      diaphragma sella was incised anteroposteriorly in the midline to the anterior
      edge of the stalk, the suprasellar cistern was entered, and the adenoma was
      selectively excised using care to limit injury to the infundibulum. After
      selective adenomectomy, Cushing's disease remitted in all patients. All patients
      were hypocortisolemic immediately after surgery and required hydrocortisone for
      up to 21 months. Apart from the adrenal axis, pituitary function was normal in
      five patients in the immediate postoperative period, including two patients with
      tumors confined to the stalk and three patients with preoperative hypothyroidism
      (one patient) and/or hypogonadism (three patients). Three others with transient
      postoperative hypothyroidism (one patient) or diabetes insipidus (two patients)
      had normal pituitary function within 7 months of surgery. One patient with
      hypothyroidism and one with hypogonadism before surgery had panhypopituitarism
      postoperatively. A patient with a microadenoma located high in the stalk next to
      the optic chiasm had bitemporal hemianopsia postoperatively. These results
      demonstrate the feasibility of achieving curative transsphenoidal resection and
      preservation of pituitary function in cases of pituitary adenomas that are
      confined to the pituitary stalk or tumors that extend superiorly within the stalk
      from an intrasellar origin.

PMID- 9285598
TI  - Histopathology of arteriovenous malformations after gamma knife radiosurgery.
AB  - Stereotactic radiosurgery effectively obliterates many arteriovenous
      malformations (AVMs). Hemodynamic changes in AVMs after radiosurgery have been
      illustrated using magnetic resonance imaging and angiography, but there have been
      no detailed reports describing the underlying histopathological changes. This
      study examines AVMs at various times after gamma knife radiosurgery (GKRS) and
      describes the histopathological changes that lead to vessel occlusion. The
      authors examined nine AVM specimens obtained 10 months to more than 5 years after
      GKRS, by using routine histopathological stains as well as immunohistochemical
      techniques to detect smooth-muscle actin, factor VIII, and type IV collagen.
      Blood vessels within the AVMs showed progressive changes leading to narrowing or
      obliteration of the lumen. The earliest changes after gamma knife irradiation
      appear to be damage to endothelial cells, followed by progressive thickening of
      the intimal layer caused by proliferation of smooth-muscle cells that elaborate
      an extracellular matrix that includes type IV collagen. Finally, cellular
      degeneration and hyaline transformation occur. For statistical correlation
      analyses, the specimens were graded according to the degree of histopathological
      change and the relative number of vessels showing such changes. Both of these
      parameters were significantly correlated with time after GKRS and with AVM size
      reduction shown on follow-up imaging studies. Gamma knife radiosurgery of AVMs
      causes endothelial damage, which induces the proliferation of smooth-muscle cells
      and the elaboration of extracellular collagen by these cells, which leads to
      progressive stenosis and obliteration of the AVM nidus. This series of
      pathological changes in AVMs after GKRS is essentially similar to the response-to
      injury model of atherosclerosis.

PMID- 9285599
TI  - Microelectrode-guided posteroventral pallidotomy for treatment of Parkinson's
      disease: postoperative magnetic resonance imaging analysis.
AB  - The authors report the postoperative magnetic resonance (MR) imaging findings in
      36 patients with advanced Parkinson's disease who underwent unilateral
      microelectrode-guided posteroventral pallidotomy. The lesions were placed within
      1 mm of the ventral border of the globus pallidus internus (GPi) to include
      pallidothalamic outflow pathways. Sequential MR studies were obtained within 1 to
      3 days postoperatively and at 6-month follow-up examination. Thirty-four (94%) of
      the 36 patients enjoyed sustained moderate or marked improvement of their
      parkinsonian symptoms 6 months postoperatively. Transient side effects occurred
      in five patients (14%), but there were no persistent complications. The pallidal
      radiofrequency lesions were prolate spheroid shaped and were composed of three
      concentric zones in the early postoperative studies. The mean volume of the
      middle zone, corresponding to the area of hemorrhagic coagulation necrosis, was
      44.4 +/- 17.6 mm3; the mean lesion volume as defined by the outer zone,
      corresponding to perilesional edema, was 262.2 +/- 111.6 mm3. Additional edema
      spreading to the internal capsule was noted in 32 of 34 cases and to the optic
      tract in 11 of 34 cases. In two patients small ischemic infarctions involving the
      corona radiata were found, and in one a venous infarction was detected. Ischemic
      infarction resulted in mild transient Broca's aphasia in one patient, but there
      was no detectable neurological deficit in the other two. The mean volume of late
      phase (6 months) lesions was 22 +/- 28.8 mm3. In three patients no lesion was
      identified despite sustained clinical improvement. The lesion was located in the
      posteroventral GPi in all cases except in one patient in whom it was confined to
      the GP externus (GPe). This 49-year-old woman did not experience sustained
      benefit. The authors found no consistent correlations between lesion size and
      location and clinical outcome as measured by a global outcome score, the Unified
      Parkinson's Disease Rating Scale motor, activities of daily living, and
      bradykinesia "off" scores or rating of dyskinesias. Lesioning of pallidal and
      subpallidal pathways may contribute to the sustained clinical benefit in this
      series. Magnetic resonance imaging analysis showed that intraoperative
      microelectrode recording facilitated accurate placement of the lesion in this
      critical area.

PMID- 9285600
TI  - The importance of pial blood supply to the development of peritumoral brain edema
      in meningiomas.
AB  - In a retrospective analysis, the authors studied the pial and dural blood
      supplies in 74 intracranial meningiomas and quantified their associated
      peritumoral brain edema (PTBE). The extent and localization of pial blush in
      relation to the total tumor volume were determined angiographically. The amount
      of edema and tumor size were calculated using computerized tomography. The edema
      tumor volume ratio was defined as Edema Index (EI). There were 49 meningiomas
      with PTBE; of those tumors, 46 were supplied by pial vessels, and three were
      supplied exclusively by dural vessels. Tumors without PTBE showed no pial blush.
      The mean EI in meningiomas with pial blush was significantly larger (EI = 3) than
      in meningiomas without pial supply (EI = 1.1; p < 0.0001). Meningiomas with a
      smaller pial supply than dural supply had a significantly smaller mean EI than
      tumors with a pial supply equal to or greater than the dural supply (EI = 2.9 vs.
      EI = 3.7; p < 0.015). In 69.9% of cases with pial blood supply, major portions of
      the edema were located adjacent to the tumor region supplied by pial vessels.
      Edema index differences among tumors of different subgroups, as defined by size
      or histology, were significantly related to the pial supply in each subset. Thus,
      pial blood supply may be associated with the development of PTBE in meningiomas.

PMID- 9285601
TI  - Endovascular treatment of ruptured posterior circulation aneurysms using
      electrolytically detachable coils.
AB  - The authors report their experience using electrolytically detachable coils for
      the treatment of ruptured posterior circulation aneurysms. Twenty-six patients
      with 28 posterior circulation aneurysms were treated. All patients were referred
      for endovascular treatment by experienced vascular neurosurgeons. Patients
      underwent follow-up angiography immediately after treatment, 1 to 6 weeks
      posttreatment, and 6 months posttreatment. Six-month follow-up angiograms
      obtained in 19 patients with 20 aneurysms demonstrated that 18 (90%) of the 20
      aneurysms were 99 to 100% occluded, one aneurysm (5%) was approximately 90%
      occluded, and one aneurysm (5%) was approximately 75% occluded. The patient with
      the aneurysm that was approximately 75% occluded needed additional treatment,
      consisting of parent artery balloon occlusion, and was considered a treatment
      failure (3.8% of patients). There was one treatment-associated mortality (3.8%)
      but no treatment-associated serious neurological or nonneurological morbidity in
      the patient group. There was no recurrent aneurysm rupture during treatment or
      during the mean 27-month follow-up period. Endovascular treatment of ruptured
      posterior circulation aneurysms with electrolytically detachable coils can be
      accomplished with low morbidity and mortality rates. The primary goal of
      treatment--preventing recurrent aneurysm--can be achieved over the short term.
      Endovascular coil occlusion will play an important role in the treatment of
      ruptured posterior circulation aneurysms, particularly if long-term efficacy in
      preventing recurrent aneurysm hemorrhage can be documented.

PMID- 9285602
TI  - Cigarette smoking-induced increase in the risk of symptomatic vasospasm after
      aneurysmal subarachnoid hemorrhage.
AB  - Vasospasm following aneurysmal subarachnoid hemorrhage (SAH) is correlated with
      the thickness of blood within the basal cisterns on the initial computerized
      tomography (CT) scan. To identify additional risk factors for symptomatic
      vasospasm, the authors performed a prospective analysis of 75 consecutively
      admitted patients who were treated for aneurysmal SAH. Five patients who died
      before treatment or were comatose postoperatively were excluded from the study.
      Of the remaining 70 patients, demographic (age, gender, and race) and clinical
      (hypertension, diabetes, coronary artery disease, smoking, alcohol abuse, illicit
      drug use, sentinel headache, Fisher grade, Hunt and Hess grade, World Federation
      of Neurological Surgeons grade, and ruptured aneurysm location) parameters were
      evaluated using multivariate logistic regression to determine factors
      independently associated with cerebral vasospasm. All patients were treated with
      hypervolemic therapy and administration of nimodipine as prophylaxis for
      vasospasm. Cerebral vasospasm was suspected in cases that exhibited (by elevation
      of transcranial Doppler velocities) neurological deterioration 3 to 14 days after
      SAH with no other explanation and was confirmed either by clinical improvement in
      response to induced hypertension or by cerebral angiography. The mean age of the
      patients was 50 years. Sixty-three percent of the patients were women, 74% were
      white, 64% were cigarette smokers, and 46% were hypertensive. Ten percent of the
      patients suffered from alcohol abuse, 19% from sentinel bleed, and 49% had a
      Fisher Grade 3 SAH. Twenty-nine percent of the patients developed symptomatic
      vasospasm. Multivariate analysis demonstrated that cigarette smoking (p = 0.033;
      odds ratio 4.7, 95% confidence interval [CI] 2.4-8.9) and Fisher Grade 3, that
      is, thick subarachnoid clot (p = 0.008; odds ratio 5.1, 95% CI 2-13.1), were
      independent predictors of symptomatic vasospasm. The authors make the novel
      observation that cigarette smoking increases the risk of symptomatic vasospasm
      after aneurysmal SAH, independent of Fisher grade.

PMID- 9285603
TI  - Follow-up evaluation of dissecting aneurysms of the vertebrobasilar circulation
      by using gadolinium-enhanced magnetic resonance imaging.
AB  - The authors assessed the reliability of magnetic resonance (MR) imaging contrast
      enhancement for the detection and follow-up evaluation of dissecting aneurysms of
      the vertebrobasilar circulation. Twenty consecutively admitted patients who
      underwent both gadolinium-enhanced MR imaging and conventional angiography were
      reviewed. Enhancement of the dissecting aneurysm was seen in all but one of the
      20 patients, including 10 (71%) of 14 patients examined in the chronic phases,
      when the T1-hyperintensity signal that corresponded to the intramural hematoma
      was unrecognizable. The enhanced area corresponded to the "pearl sign" or
      aneurysm dilation noted on the comparable angiogram. On follow-up MR studies
      enhancement had spontaneously disappeared in four patients at a time when
      comparable vertebral angiograms revealed disappearance of the aneurysm dilation.
      The enhancement persisted in five of nine patients examined more than 24 weeks
      after symptom onset; in all five patients the aneurysm dilation remained on
      comparable angiograms. Dynamic MR studies showed rapid and remarkable
      enhancements with their peaks during the immediate dynamic phase after injection
      of the contrast material. The authors conclude that gadolinium-enhanced MR
      imaging is useful for the detection and follow-up evaluation of dissecting
      aneurysms of the vertebrobasilar circulation.

PMID- 9285604
TI  - Surgical management and seizure outcome in patients with tuberous sclerosis.
AB  - The authors report the results obtained in 11 patients with tuberous sclerosis
      (TS) who underwent cortical resection surgery for medically intractable epilepsy.
      Patients' ages at time of surgery ranged from 3 to 46 years (mean 19.6 years).
      Preoperative epileptiform electroencephalographic abnormalities were focal spike
      wave discharges in six patients (55%), multifocal in four patients (36%), and
      generalized in one patient (9%). In the multifocal and generalized groups, all
      patients (45%) were evaluated by means of subdural grid and strip electrode
      recordings, whereas electrophysiological localization in the remaining patients
      was derived from ictal and interictal scalp recordings. The seizure foci were
      found to be extratemporal in six patients (55%) and temporal in five patients
      (45%). Surgical intervention consisted of craniotomy and seizure foci resection
      guided by electrocorticographic monitoring and functional mapping in five awake
      (45%) and six asleep (55%) patients. Neuropathological examination of the
      resected seizure foci revealed cortical tubers in eight patients and diffuse
      gliosis in three patients. Follow up ranged from 8 to 127 months (mean 35
      months). Six patients (55%) were seizure free, half of whom were not receiving
      antiepileptic drugs (AEDs); three patients (27%) had a greater than 70% reduction
      in seizure frequency, although they required AEDs; one patient (9%) had a 50%
      temporary reduction in seizure frequency during the initial 6-month postoperative
      period; and one patient (9%) was lost to follow-up study. From this small but
      adequately followed patient population with TS, the authors conclude that
      cortical resection of seizure foci tailored to electrocorticographic findings and
      functional mapping is encouraging for this difficult to manage patient population
      with medically intractable epilepsy.

PMID- 9285605
TI  - Evaluation with evoked and spontaneous electromyography during lumbar
      instrumentation: a prospective study.
AB  - The neuroanatomical structures that approximate the bony pedicles of the lumbar
      spine allow little room for technical error or compromise of the bone during
      pedicle screw insertion. Currently available neurophysiological monitoring
      techniques detect compromised bone and nerve root injury after it occurs. The
      purpose of this prospective study is to evaluate the reliability and efficacy of
      a unique neurophysiological monitoring technique. This technique provides
      immediate evaluation of pedicle cortical bone integrity in patients undergoing
      lumbar fusion with instrumentation by using electrified surgical instruments
      throughout the pedicle screw fusion procedure. Spontaneous electromyographic
      (EMG) activity was also monitored. Intraoperative evoked EMG stimulation was
      performed using a pedicle probe and feeler as monopolar stimulators during the
      insertion of 164 pedicle bone screws in 32 patients. The EMG response to
      subthreshold stimulation intensities indicated cortical bone compromise.
      Immediate and conclusive feedback via evoked EMG activity using stimulating
      pedicle probes in appropriate muscle groups was successful in identifying pedicle
      cortical bone compromise in four patients. One false-negative evoked EMG study
      was noted but was identified via spontaneous EMG activity. Intraoperative EMG
      monitoring alerted the surgeon that redirection of the pedicle probe or screw was
      necessary to avoid nerve root irritation or injury and served as an early warning
      system. Evoked EMG stimulation proved to be reliable and efficacious, especially
      when used in combination with spontaneous EMG. This technique may provide an
      added safeguard during implant placement procedures at centers where
      intraoperative neurophysiological monitoring is routinely performed.

PMID- 9285606
TI  - Ganglion cyst involvement of peripheral nerves.
AB  - Despite their benign histological appearance and the current literature composed
      primarily of case reports with favorable outcomes, ganglion cysts involving
      peripheral nerves (GCPNs) can cause permanent neurological deficits. The authors
      present a 27-year Louisiana State University Medical Center (LSUMC) experience
      with the surgical management of GCPNs. From 1968 to 1995, 27 patients were
      surgically treated for 27 cysts that involved nerves at nine locations. Cysts of
      the peroneal nerve were the most common, comprising 52% of the cases. Motor
      deficit, pain, and sensory changes were present in 83%, 78%, and 48% of cases,
      respectively. A history of acute trauma was noted in 22%. The mean follow-up
      duration in these cases was 61 months. Motor recovery was good in only 58% of
      cases and was related to the severity of the preoperative motor deficit. Pain
      resolved or was significantly improved in 89% of cases. Five patients underwent
      nine procedures before referral to LSUMC for treatment of recurrence of their
      ganglion cysts. None of these patients suffered recurrence after undergoing
      surgery at LSUMC. However, four additional patients (17%) experienced a total of
      six recurrences after undergoing their initial procedure. The mean time to
      recurrence for the patient group as a whole was 16 months. On the basis of their
      experience, the authors conclude that GCPNs can behave in an aggressive fashion.
      Patients should be counseled preoperatively about the potential for limited motor
      recovery and a significant chance for recurrence.

PMID- 9285607
TI  - Intrathecally administered baclofen for treatment of children with spasticity of
      cerebral origin.
AB  - Management of severe spasticity in children is often a difficult problem. Orally
      administered medications generally offer limited benefits. This study examines
      the value of intrathecally administered baclofen in the treatment of 19 children
      with severe spasticity of cerebral origin: eight of whom sustained brain injury
      associated with trauma, near drowning, or cardiac arrest; 10 with cerebral palsy
      (spastic quadriplegia); and one child with Leigh's disease. At the time of entry
      into the study, patients ranged from 4 to 19 years of age, and all were
      completely dependent on caretakers for activities of daily living. Children who
      responded positively to a trial dose of intrathecal baclofen underwent insertion
      of a drug delivery system for continuous infusion. This was followed by a double
      blind trial of baclofen or placebo and follow-up review at 3 and 6 months, and
      yearly thereafter. Seven children did not undergo pump implantation because of
      excess sedation or poor response. The 12 remaining children have been followed
      for a period of 1 to 5 years. Favorable responses were present in all 12 children
      as determined by the Ashworth Scale, with the greatest benefit being reduction of
      lower limb tone. Except in the case of one child who had reduction in lower limb
      tone that resulted in difficulty with transfers, the caretakers all reported
      significant benefits from intrathecal baclofen, with improvement in muscle tone,
      behavior, sitting, and general ease of care being most commonly noted. Central
      side effects were seen in some children who received continuous intrathecal
      baclofen infusion and included hypotension (two patients), bradycardia (two),
      apnea or respiratory depression (two), and sedation (one). During a total of 568
      months of pump operation there were 10 mechanical complications, including two
      related to pump or side port failure and eight related to catheter kinks,
      extrusions, or dislodgment. Pump pocket effusion occurred in five children and a
      cerebrospinal fluid fistula was seen in one child. Local infection occurred in
      three children and meningitis in two children. The results demonstrate the
      potential value of continuous intrathecal baclofen infusion for treatment of
      severe spasticity of cerebral origin. However, this treatment can result in
      significant complications and more experience is required before the long-term
      benefits can be determined.

PMID- 9285608
TI  - Prospective assessment of continuous intrathecal infusion of baclofen for
      spasticity caused by acquired brain injury: a preliminary report.
AB  - Twelve consecutive patients with severe spasticity and hypertonia following
      acquired brain injury were treated with continuous intrathecal infusion of
      baclofen via an implanted, programmable infusion pump-catheter system for a
      minimum of 3 months. In every case intrathecal baclofen therapy resulted in a
      statistically significant reduction in upper- and lower-extremity tone, spasm
      frequency, and reflexes, contributing to improved functional abilities. There
      were no untoward side effects or complications associated with treatment. This
      preliminary assessment indicates that intrathecal administration of baclofen is
      effective in treating the disabling spasticity caused by acquired brain injury in
      selected patients.

PMID- 9285609
TI  - Role of glial filaments in cells and tumors of glial origin: a review.
AB  - In the adult human brain, normal astrocytes constitute nearly 40% of the total
      central nervous system (CNS) cell population and may assume a star-shaped
      configuration resembling epithelial cells insofar as the astrocytes remain
      intimately associated, through their cytoplasmic extensions, with the basement
      membrane of the capillary endothelial cells and the basal lamina of the glial
      limitans externa. Although their exact function remains unknown, in the past,
      astrocytes were thought to subserve an important supportive role for neurons,
      providing a favorable ionic environment, modulating extracellular levels of
      neurotransmitters, and serving as spacers that organize neurons. In
      immunohistochemical preparations, normal, reactive, and neoplastic astrocytes may
      be positively identified and distinguished from other CNS cell types by the
      expression of the astrocyte-specific intermediate filament glial fibrillary
      acidic protein (GFAP). Glial fibrillary acidic protein is a 50-kD
      intracytoplasmic filamentous protein that constitutes a portion of, and is
      specific for, the cytoskeleton of the astrocyte. This protein has proved to be
      the most specific marker for cells of astrocytic origin under normal and
      pathological conditions. Interestingly, with increasing astrocytic malignancy,
      there is progressive loss of GFAP production. As the human gene for GFAP has now
      been cloned and sequenced, this review begins with a summary of the molecular
      biology of GFAP including the proven utility of the GFAP promoter in targeting
      genes of interest to the CNS in transgenic animals. Based on the data provided
      the authors argue cogently for an expanded role of GFAP in complex cellular
      events such as cytoskeletal reorganization, maintenance of myelination, cell
      adhesion, and signaling pathways. As such, GFAP may not represent a mere
      mechanical integrator of cellular space, as has been previously thought. Rather,
      GFAP may provide docking sites for important kinases that recognize key cellular
      substrates that enable GFAP to form a dynamic continuum with microfilaments,
      integrin receptors, and the extracellular matrix.

PMID- 9285610
TI  - Induction of hypercontractility in human cerebral arteries by rewarming following
      hypothermia: a possible role for tyrosine kinase.
AB  - Induction of hypothermia is used routinely in neurosurgical and cardiovascular
      operations to protect the brain from ischemic insult. However, despite a plethora
      of experimental evidence supporting the use of hypothermia to protect the brain
      from ischemia, clinical experience using deliberate hypothermia in humans has not
      shown a convincing benefit. The authors tested the hypothesis that hypothermia
      and rewarming alter tone in human cerebral vessels and may interfere with
      cerebral perfusion in the setting of deliberate hypothermia. They examined human
      cerebral arteries during hypothermia (32 degrees C and 17 degrees C) and during
      rewarming to delineate the direct effects of cooling and rewarming on
      cerebrovascular tone. Artery segments obtained from autopsy material and from
      specimens excised at elective temporal lobectomies were tested in tissue baths
      using isometric tension measurements. Temperature-induced changes in vascular
      tone were measured and quantified with respect to contractile responses to
      serotonin (5-HT; 10(-6) M). Cooling induced mild relaxation in cerebral vessels (
      38 +/- 12% 5-HT response in 50 vessels from autopsy specimens, -69 +/- 10% 5-HT
      response in 51 vessels from lobectomy specimens). On rewarming, vessels
      contracted significantly beyond their baseline tone (108 +/- 18% 5-HT response in
      50 vessels from autopsy specimens, 42 +/- 12% 5-HT response in 51 vessels from
      lobectomy specimens). Rewarming-induced hypercontractility was inhibited by the
      tyrosine kinase inhibitor genistein (-5 +/- 7% vs. 70 +/- 23% 5-HT response,
      genistein vs. control, 14 segments, p < 0.05) and enhanced by the tyrosine
      phosphatase inhibitor sodium orthovanadate (339 +/- 54% vs. 104 +/- 20% 5-HT
      response, sodium orthovanadate vs. control, five segments, p < 0.05), indicating
      a possible role for tyrosine kinase activation in the rewarming-induced
      contraction.

PMID- 9285611
TI  - Occurrence of severe vasospasm following intraventricular hemorrhage from an
      arteriovenous malformation. Report of two cases.
AB  - The authors present two rare cases of severe cerebral vasospasm following the
      rupture of arteriovenous malformations (AVMs). Computerized tomography revealed
      intracerebral hemorrhage in the thalamus in one case and in the putamen in the
      other, both accompanied by cast formation of intraventricular clots without
      radiological evidence of subarachnoid hemorrhage. Initial angiograms showed
      arterial narrowing of the bilateral internal carotid arteries in the supraclinoid
      portion but failed to demonstrate an arteriovenous shunt. Subsequent angiograms
      clearly demonstrated the existence of an AVM. Radiological features and possible
      mechanisms are discussed.

PMID- 9285612
TI  - Resection of a large, high-flow arteriovenous malformation during hypotension and
      hypothermia induced by a percutaneous cardiopulmonary support system. Case
      report.
AB  - The key to successful surgical resection of cerebral arteriovenous malformations
      (AVMs) is control of bleeding and cerebral swelling. Induced hypotension is one
      of the most valuable means of achieving this control. The authors introduced
      induced hypotension with mild hypothermia by using a percutaneous cardiopulmonary
      support system (PCPS) to resect a large, high-flow AVM. The efficacy and
      technical points of this method are discussed. The PCPS, whose entire
      intraluminal surface was coated with heparin, was established through a
      transfemoral route. During resection of the AVM, a mean arterial blood pressure
      of 60 mm Hg and a mean body temperature of 30 degrees C were easily maintained by
      regulating the flow rate of the PCPS and by blood cooling. The activated
      coagulation time was maintained at approximately 250 seconds with a minimum
      systemic administration of heparin. The authors report the case of a 30-year-old
      woman who presented with intraventricular hemorrhage and was diagnosed as having
      a large, high-flow AVM located in the left sylvian fissure. The AVM was fed by
      the left middle, posterior, and anterior cerebral arteries and drained by the
      many cortical ascending veins and the basal vein. The patient underwent surgery
      after hypotension and hypothermia had been induced via the PCPS method. Induced
      hypotension decreased the tension of the nidus and made its dissection easier.
      The AVM was totally resected and no hemostatic difficulties were encountered. On
      the basis of the authors' experience, they suggest that hypotension and
      hypothermia induced by using the PCPS is a powerful tool for the successful
      resection of large, high-flow AVMs.

PMID- 9285613
TI  - Papillary adenoma of endolymphatic sac origin: a temporal bone tumor in von
      Hippel-Lindau disease. Case report.
AB  - This report describes a patient with von Hippel-Lindau disease who presented with
      an 8-year history of a slow-growing, locally invasive vascularized lesion of the
      temporal bone involving the cerebellopontine angle. The mass, studied by
      computerized tomography scanning and magnetic resonance imaging techniques, was
      partly cystic in appearance. After removal of the mass, pathological studies
      confirmed a papillary cystic tumor with characteristics that have been described
      in tumors with an endolymphatic sac origin. These rare neoplasms constitute a
      distinct pathological entity and deserve wider recognition.

PMID- 9285614
TI  - Stereotactic radiosurgical treatment of sphenopalatine neuralgia. Case report.
AB  - Sphenopalatine neuralgia is a rare craniofacial pain syndrome that is
      characterized by unilateral pain in the orbit, mouth, nose, and posterior mastoid
      process. During attacks of pain, vasomotor activity often results in ipsilateral
      nasal drainage, eye irritation, and lacrimation. The authors present a patient
      with a 15-year history of sphenopalatine neuralgia who underwent stereotactic
      radiosurgery targeted at the sphenopalatine ganglion, with initial pain relief,
      and repeated radiosurgery 17 months later for partial pain recurrence. Two years
      following radiosurgery, the patient is pain free, no longer suffering from nasal
      discharge and eye irritation.

PMID- 9285615
TI  - Teflon-induced granuloma following treatment of trigeminal neuralgia by
      microvascular decompression. Report of two cases.
AB  - The authors report two cases of Teflon-induced granuloma occurring as a result of
      microvascular decompression using Teflon wool for the treatment of trigeminal
      neuralgia (TN). Teflon, which is used to separate a compressing vessel from the
      root entry zone (REZ) of the trigeminal nerve at the brainstem, is presumed to be
      an inert material. In the two cases reported here, however, Teflon induced a
      foreign body reaction at the REZ, causing recurrence of TN. The patients' pain
      was cured by complete decompression or partial sensory rhizotomy of the
      trigeminal sensory root at reoperation. Teflon-induced granuloma has occurred in
      1.3% of the authors' series of 155 patients with TN treated using microvascular
      decompression. Recommendations for avoiding this complication are offered.

PMID- 9285616
TI  - Spondyloptotic fracture of the cervical spine in a pregnant, anemic Jehovah's
      Witness: technical and ethical considerations. Case report.
AB  - The authors present the case of a 15-year-old Jehovah's Witness with a hematocrit
      level of 19% who was 4 months pregnant and had a two-level spondyloptotic
      cervical spine fracture. The patient was transferred to Georgetown University
      Medical Center with C-5 quadriplegia 3 weeks after having been injured in an
      automobile collision. The neurosurgical issues in this case included addressing a
      rare cervical spine injury, assessing and treating a vertebral artery injury, and
      performing surgery on a pregnant minor with severe anemia who held strong
      Jehovah's Witness beliefs. An ethics consultation was convened to determine the
      validity of a pregnant minor's refusal to undergo transfusion on the grounds of
      her religious beliefs. This case illustrates the potential benefits of thorough
      technical and ethical evaluations and reveals how they may contribute to the
      delivery of care in complex neurosurgical cases. To the authors' knowledge, this
      is the first two-level spondyloptotic cervical spine fracture dislocation to be
      reported in the literature. The added complexities of the case, given that the
      patient was an anemic, adolescent, pregnant Jehovah's Witness who refused blood
      transfusion, also appear to be unprecedented.

PMID- 9285617
TI  - Spinal echinococcal cyst: treatment using computerized tomography-guided needle
      aspiration and hypertonic saline irrigation. Case report.
AB  - A multilocular extradural cervical spinal hydatid cyst that causes severe spinal
      cord compression and quadriplegia is relatively rare and difficult to treat. In a
      patient with this disorder, computerized tomography-guided needle aspiration of
      the cyst loculations and irrigation using hypertonic saline eliminated the need
      for emergency surgery and provided complete resolution of the patient's
      quadriplegia. The subsequent course of the disease was controlled by treatment
      with albendazole. Magnetic resonance imaging performed 4 months after the
      procedure demonstrated collapsed cysts and absence of spinal cord compression.

PMID- 9285618
TI  - Iatrogenic intradiploic meningoencephalocele. Case report.
AB  - The authors present the case of a 6-year-old girl who developed a right frontal
      intradiploic meningoencephalocele following an accidental dural tear produced
      during surgery for craniosynostosis. Although rare, growing skull fractures have
      been described in at least eight cases following the accidental laceration of the
      dura mater in the course of craniosynostosis repair. These cases closely resemble
      those produced by accidental trauma to the growing skull. However, the
      intradiploic location of a meningoencephalocele following surgery for
      craniosynostosis has not been documented previously. This patient presented with
      headache and a frontal tumor of bonelike consistency. Radiographs and
      computerized tomography scans of the skull revealed an intraosseous cyst, whereas
      magnetic resonance imaging demonstrated cerebral tissue herniation within the
      intradiploic tumor. Surgical treatment consisted of duraplasty and cranioplasty,
      which achieved good functional and cosmetic results. The pathogenesis of this
      unusual lesion is discussed and compared with the hypotheses advanced for
      explaining posttraumatic intradiploic cysts.

PMID- 9285619
TI  - Cervical intramedullary lipoma with intracranial extension in an infant. Case
      illustration.

PMID- 9285621
TI  - Tremor caused by ipsilateral chronic subdural hematoma. Case illustration.

PMID- 9285620
TI  - Suture granuloma mimicking a lumbar disc recurrence. Case illustration.

PMID- 9285622
TI  - Bone flap fixation: a new technique. Technical note.
AB  - A new fixation technique for bone flaps is described. This technique avoids the
      use of hardware external to the skull in hairless areas where it may prove
      unsightly in patients with a thin scalp. The insertion of pins into the middle
      table of the skull firmly fixes bone flaps at one edge, eliminating the need for
      external plates at that site.

PMID- 9285623
TI  - Charles Labbe (1851-1889).
AB  - The vein of Labbe is a very important structure and every neurosurgeon is
      acquainted with its anatomy. Because of the recent increasing interest and
      experience in skull base surgery, the vein of Labbe has received a great deal of
      attention. Intraoperative damage to this vein should be avoided and several
      methods to prevent this have been described. Despite these developments, nothing
      is written in the neurosurgical literature about the man who described this vein
      for the first time: Charles Labbe. The authors therefore conducted an extensive
      search of the literature and uncovered several public records in France to learn
      more about Charles Labbe.

PMID- 9285625
TI  - Tumor in normal brain.

PMID- 9285624
TI  - Diagnosis of root avulsions.

PMID- 9285626
TI  - Minor head injury.

PMID- 9285627
TI  - Ventriculostomy or subgaleal shunting?

PMID- 9285628
TI  - Antifibrinolytic therapy.

PMID- 9285629
TI  - Growth factor and cytokine-regulated hyaluronan-binding protein TSG-6 is
      localized to the injury-induced rat neointima and confers enhanced growth in
      vascular smooth muscle cells.
AB  - Hyaluronan (HA) and HA-binding proteins have been implicated in a diverse array
      of biological processes, including development, tissue repair, and tumor
      invasion. However, the role of HA and HA-binding proteins in atherosclerosis and
      restenosis is poorly understood. PS4 (TSG-6) is a HA-binding protein expressed by
      cultured vascular smooth muscle cells (SMCs) in response to serum and growth
      factor stimulation. To delineate a possible role for TSG-6 in vascular disease
      progression, we have characterized its expression in cultured SMCs and in a rat
      vascular injury model, and we have studied the effect of constitutive
      overexpression of TSG-6 on SMC behavior. We found that interleukin-1 (IL-1) but
      not tumor necrosis factor or interleukin-6 was able to stimulate TSG-6 expression
      in SMCs. The IL-1 pathway could be distinguished from the growth factor pathway
      by its insensitivity to protein synthesis inhibitors. Furthermore, epidermal
      growth factor, fibroblast growth factor-1, and transforming growth factor-beta1
      were all capable of augmenting maximum IL-1-induced expression of TSG-6. To gain
      further insight into the function of TSG-6 in SMCs, we examined the effect of
      constitutive overexpression of TSG-6 on these cells. We found that TSG-6
      overexpressing cells grew >50% faster than control cells. Furthermore, this
      growth advantage became more evident in the absence of serum growth factors, with
      an average increase in cell number of 118% over control cells after 6 days.
      Consistent with these in vitro data, we observed intense immunostaining for TSG-6
      in proliferating SMCs in the rat neointima after injury, whereas only an
      occasional cell was positive for TSG-6 in the medial layer and in nonballooned
      arteries. We conclude that the expression of TSG-6 is tightly controlled by
      growth factors and cytokines via two distinct pathways in SMCs and that
      overexpression of TSG-6 confers a growth advantage to these cells.

PMID- 9285630
TI  - Endothelial cells of the human microvasculature express epidermal fatty acid
      binding protein.
AB  - Epidermal fatty acid-binding protein (E-FABP), previously characterized in human
      keratinocytes, is a cytoplasmic protein of 15 kD that specifically binds fatty
      acids (FAs). Previous PAGE-immunoblotting studies indicated that several human
      tissues display an immunoreactive band with an electrophoretic mobility identical
      to that of E-FABP. The aim of this study was to determine in which cells, other
      than keratinocytes, E-FABP might be expressed. By immunohistochemistry, we show
      that E-FABP is expressed in endothelial cells of the microvasculature of the
      placenta, heart, skeletal muscle, small intestine, lung, and renal medulla.
      Interestingly, in lung, a tissue of endodermal origin, E-FABP staining was also
      localized to secretory cells, ie, Clara cells, goblet cells, and probably a
      subpopulation of pneumocytes. RNA isolated from cultured human umbilical vein and
      normal human dermal microvascular endothelial cells was analyzed by reverse
      transcriptase polymerase chain reaction (RT-PCR). Southern blotting and
      sequencing of the cloned RT-PCR products demonstrate that endothelial E-FABP is
      identical to keratinocyte E-FABP. These data suggest that E-FABP-mediated FA
      transport occurs at the level of the microvasculature in several FA target
      organs.

PMID- 9285631
TI  - Exacerbation of cerebral injury in mice that express the P-selectin gene:
      identification of P-selectin blockade as a new target for the treatment of
      stroke.
AB  - There is currently a stark therapeutic void in the treatment of evolving stroke.
      Although P-selectin is rapidly expressed by hypoxic endothelial cells in vitro,
      the functional significance of P-selectin expression in stroke remains
      unexplored. In order to identify the pathophysiological consequences of P
      selectin expression and to identify P-selectin blockade as a potential new
      approach for the treatment of stroke, experiments were performed using a murine
      model of focal cerebral ischemia and reperfusion. Early P-selectin expression in
      the postischemic cerebral cortex was demonstrated by the specific accumulation of
      radiolabeled anti-murine P-selectin IgG, with the increased P-selectin expression
      localized to the ipsilateral cerebral microvascular endothelial cells by
      immunohistochemistry. In experiments designed to test the functional significance
      of increased P-selectin expression in stroke, neutrophil accumulation in the
      ischemic cortex of mice expressing the P-selectin gene (PS +/+) was demonstrated
      to be significantly greater than that in homozygous P-selectin-null mice (PS -/
      ). Reduced neutrophil influx was accompanied by greater postischemic cerebral
      reflow (measured by laser Doppler) in the PS -/- mice. In addition, PS -/- mice
      demonstrated smaller infarct volumes (5-fold reduction, P<.05) and improved
      survival compared with PS +/+ mice (88% versus 44%, P<.05). Functional blockade
      of P-selectin in PS +/+ mice using a monoclonal antibody directed against murine
      P-selectin also improved early reflow and stroke outcome compared with control
      mice, with reduced cerebral infarction volumes noted even when the blocking
      antibody was administered after occlusion of the middle cerebral artery. These
      data are the first to demonstrate a pathophysiological role for P-selectin in
      stroke and suggest that P-selectin blockade may represent a new therapeutic
      target in the treatment of stroke.

PMID- 9285632
TI  - Flow-induced vascular remodeling in the rat carotid artery diminishes with age.
AB  - Vascular remodeling is regulated by a combination of hemodynamic, environmental,
      and genetic factors and may be influenced by age. To evaluate age-dependent
      remodeling in rats, we developed and used a quantitative highly reproducible
      model of carotid flow alteration. Fourteen juvenile (99+/-3 g) and 9 adult (199+/
      5 g) male inbred Fischer rats underwent ligation of the left internal and
      external carotid arteries under anesthesia. Left common carotid blood flow
      immediately decreased by approximately 93%, whereas flow in the contralateral
      carotid increased by approximately 46%. After 4 weeks, the left carotid outer
      diameter (OD) significantly decreased in both juvenile and adult rats (as
      measured in vivo and by histological morphometry) compared with sham-operated
      rats. Changes in shear stress acutely mirrored the changes in blood flow. OD
      increased and shear stress returned to initial values after chronic exposure to
      increased flow in juvenile but not adult rats. To develop a simple quantitative
      index of remodeling that would not require killing the animals, we measured the
      OD in vivo and compared the ratio of right to left OD (OD ratio [ODR]) between
      groups. The initial ODR for all groups was approximately 1.0. After 4 weeks of
      altered flow, the ODR was significantly greater in juvenile than in adult rats
      (1.48+/-0.05 versus 1.29+/-0.04, respectively; P=.030), indicating that juvenile
      rats experienced more extensive remodeling than did the adult rats. We also found
      that unilateral carotid ligation caused a left versus right difference in
      endothelial NO synthase protein levels after 4 weeks that was not present in the
      sham-operated animals. Thus, the model described here shows that flow-induced
      vascular remodeling is dependent on age and supports the hypothesis that the
      driving force for remodeling involves shear stress and possibly NO. Because the
      model is quantitative, it allows dissection of the genetic factors that regulate
      remodeling in inbred rat strains.

PMID- 9285633
TI  - Platelet-derived growth factor ligand and receptor expression in response to
      altered blood flow in vivo.
AB  - Blood flow and the tractive force shear stress are important determinants of
      artery caliber, and reduced shear predisposes arteries to intimal thickening and
      atherosclerosis. The molecular basis for shear-induced changes in artery wall
      structure is poorly defined. A number of factors associated with normal and
      pathological artery wall remodeling are induced by shear stress in endothelial
      cell cultures. These include platelet-derived growth factor (PDGF), a potent
      mitogen, chemoattractant, and vasoconstrictor. To determine whether similar
      changes occur in vivo, we examined the effects of reduced blood flow on
      endothelial cell PDGF expression and proliferation in the rat carotid artery.
      Branches of the right internal and external carotid arteries were ligated,
      reducing common carotid artery blood flow from 8.0+/-0.6 to 0.5+/-0.1 mL/min
      while increasing flow in the left carotid from 7.1+/-0.6 to 10.8+/-0.7 mL/min.
      Shear stress following the procedure was 1.4+/-0.2 and 33.4+/-1.1 dyne/cm2 in
      carotids with reduced blood flow (RF) and increased blood flow (IF),
      respectively. Arteries were harvested 6, 24, 48, or 72 hours after ligation,
      perfusion-fixed, and opened longitudinally. Endothelial cell proliferation
      (bromodeoxyuridine [BrdU] labeling) was assessed en face at 24, 48, and 72 hours;
      expression of mRNA for PDGF-A and -B chains and PDGF alpha- and beta-receptors
      (in situ hybridization) was determined at 6, 48, and 72 hours after unilateral
      flow reduction. RF induced endothelial cell proliferation, which peaked at 48
      hours (RF BrdU labeling: 24 hours, 0.4+/-0.2%; 48 hours, 7.2+/-2.0%; and 72
      hours, 4.1+/-0.6%; n=5). PDGF-B expression increased in RF compared with IF
      endothelium within 48 hours and persisted at 72 hours (percent labeling
      [RF/IFx100]: 6 hours, 76+/-20%; 48 hours, 395+/-179%; and 72 hours, 208+/-44%;
      n=3). PDGF-A expression was similarly increased in RF endothelium. In contrast,
      expression of PDGF alpha- and beta-receptors was undetectable in RF and IF
      endothelium at all times. We conclude that endothelial cell PDGF ligand
      expression is induced by reduced shear stress in vivo and may play an important
      role in flow-mediated remodeling and atherogenesis.

PMID- 9285634
TI  - Effects of changes in blood flow rate on cell death and cell proliferation in
      carotid arteries of immature rabbits.
AB  - Spontaneous and experimental changes in arterial blood flow rates affect tissue
      accumulation in developing arteries. To examine whether cell proliferation and/or
      cell death are affected by alterations in blood flow, we ligated the left
      external carotid artery of 3-week-old rabbits, which reduces left common carotid
      blood flow by 71%. In control arteries and after 2 days of flow reduction,
      agarose gel electrophoresis of DNA extracted from all carotid arteries resolved
      multiple low molecular weight bands characteristic of apoptosis; however, DNA
      fragmentation in arteries carrying reduced blood flow was 2.5-fold higher than
      that of control arteries. The effect of reduced blood flow on cell death
      subsequently waned but remained significant at 7 days. Cell death in carotid
      arteries was also detected by in vivo uptake of propidium iodide, a DNA-binding
      fluorescent dye that labels the nuclei of nonviable cells. Both smooth muscle and
      endothelial cells exhibited large and statistically significant increases in
      labeling index in the flow-reduced artery. Propidium iodide-labeled cells were
      cleared from the vessel wall within 1 to 4 hours of labeling, and nuclear
      staining displayed condensation (clumping) of chromatin in all labeled cells at
      later time points. This time course and nuclear morphology and the rapid
      clearance of labeled cells are consistent with death via apoptosis. Many
      propidium iodide-positive cells did not display chromatin condensation
      immediately after labeling; however, this was also true of cultured endothelial
      cells that were driven into apoptosis with sphingomyelinase treatment and then
      double-labeled with propidium iodide and the apoptosis marker annexin V. We infer
      that propidium iodide can label apoptotic vascular cells before these cells
      display chromatin condensation that is detectable with fluorescence labeling of
      DNA. Replication rates of smooth muscle and endothelial cells, determined by 5
      bromo-2'-deoxyuridine uptake, were inhibited by >75% with decreased blood flow.
      The inhibition of proliferation was unabated after 7 days of reduced flow. These
      findings indicate that the coordinated regulation of cell death and cell
      proliferation, in response to changes in arterial blood flow rates, contributes
      to arterial remodeling during development.

PMID- 9285635
TI  - Comparison of aorta and pulmonary artery: I. Early cholesterol accumulation and
      relative susceptibility to atheromatous lesions.
AB  - In rabbits, the pulmonary artery and the aorta are susceptible to
      atherosclerosis. However, susceptibility of the pulmonary artery, compared with
      the aortic arch, to atherosclerosis and the relationship between the accumulation
      of cholesterol during the early stages of atherogenesis and the development of
      atheromatous lesions for these arterial regions remain to be clarified.
      Cholesterol concentrations for the pulmonary artery and aorta were measured in
      normal rabbits and in rabbits fed a 0.5% cholesterol diet for 8, 12, and 16 days
      and 17 weeks. In normal rabbits, the rank order of arterial cholesterol
      concentrations was pulmonary artery>aortic arch>descending thoracic aorta, with
      concentrations of total and nonesterified cholesterol 17% and 25% (both P<.05)
      greater, respectively, for the pulmonary artery than for the descending thoracic
      aorta. Rank order remained the same during 16 days of cholesterol feeding, but
      differences between arterial regions were exaggerated. After rabbits were fed
      cholesterol for 16 days, total and esterified cholesterol concentrations were 57%
      and 920% (both P<.01) greater, respectively, for the pulmonary artery than for
      the descending thoracic aorta, with much smaller differences between the aortic
      regions. In contrast, after rabbits were fed cholesterol for 17 weeks,
      concentrations of total, esterified, and nonesterified cholesterol were similar
      for the pulmonary artery and aortic arch, but these forms of cholesterol were
      increased 100%, 130%, and 53% (all P<.03), respectively, for the aortic arch
      compared with the descending thoracic aorta. Cholesterol concentrations for the
      pulmonary artery were positively associated with those for the aortic regions
      during the first 16 days of cholesterol feeding, but for rabbits fed cholesterol
      for 17 weeks the associations were either negative or absent. These results
      indicate that relative rates of cholesterol accumulation in the pulmonary artery
      and aorta differ at different stages of atherogenesis and suggest that the
      balance between processes that deliver cholesterol to, and remove cholesterol
      from, the artery may change in different ways in these arterial regions during
      atherogenesis.

PMID- 9285636
TI  - Comparison of aorta and pulmonary artery: II. LDL transport and metabolism
      correlate with susceptibility to atherosclerosis.
AB  - The pulmonary artery and the aorta are similarly susceptible to atherosclerosis
      in rabbits. However, the mechanism(s) that accounts for this is not yet known.
      This study investigated the hypothesis that one or more aspects of arterial low
      density lipoprotein (LDL) transport and metabolism might explain the similar
      susceptibility of the aortic arch and pulmonary artery to atherosclerosis and the
      increased susceptibility of these arterial regions compared with the descending
      thoracic aorta. We determined permeability to LDL, rates of LDL degradation, and
      concentrations of undegraded LDL for the intima-media of normal rabbits and those
      fed cholesterol for approximately 8 days. Intima-media permeability did not
      differ between corresponding arterial regions of normal rabbits and rabbits fed
      cholesterol for 8 days and was similar for the aortic arch and pulmonary artery.
      Rates of LDL degradation and concentrations of undegraded LDL for the intima
      media were influenced by cholesterol feeding. These measures were reduced in
      fractional terms but increased in absolute terms as a result of
      hypercholesterolemia, without differences between corresponding parameters for
      the pulmonary artery and aortic arch. However, permeability to LDL, rates of LDL
      degradation, and concentrations of undegraded LDL were increased for the intima
      media of the aortic arch compared with the descending thoracic aorta. Similar,
      although not always significant, trends were evident for the comparison of the
      pulmonary artery and descending thoracic aorta. Differences in LDL transport and
      metabolism and changes after feeding cholesterol for 8 days parallel the relative
      susceptibility to atherosclerosis for the three arterial regions studied. These
      results support the role of arterial LDL transport and metabolism in
      atherogenesis and potentially provide a mechanistic explanation for the
      differences in susceptibility to atherosclerosis for these three arterial
      regions.

PMID- 9285637
TI  - Estrogen upregulates endothelial nitric oxide synthase gene expression in fetal
      pulmonary artery endothelium.
AB  - NO, produced by endothelial NO synthase (eNOS), is a key mediator of pulmonary
      vasodilation during cardiopulmonary transition at birth. The capacity for NO
      production is maximal at term because pulmonary eNOS expression increases during
      late gestation. Since fetal estrogen levels rise markedly during late gestation
      and there is indirect evidence that the hormone enhances nonpulmonary NO
      production in adults, estrogen may upregulate eNOS in fetal pulmonary artery
      endothelium. Therefore, we studied the direct effects of estrogen on eNOS
      expression in ovine fetal pulmonary artery endothelial cells (PAECs). Estradiol
      17beta caused a 2.5-fold increase in NOS enzymatic activity in PAEC lysates. This
      effect was evident after 48 hours, and it occurred in response to physiological
      concentrations of the hormone (10(-10) to 10(-6) mol/L). The increase in NOS
      activity was related to an upregulation in eNOS protein expression, and eNOS mRNA
      abundance was also enhanced. Estrogen receptor antagonism with ICI 182,780
      completely inhibited estrogen-mediated eNOS upregulation, indicating that
      estrogen receptor activation is necessary for this response. In addition,
      immunocytochemistry revealed that fetal PAECs express estrogen receptor protein.
      Furthermore, transient transfection assays with a specific estrogen-responsive
      reporter system have demonstrated that the endothelial estrogen receptor is
      capable of estrogen-induced transcriptional transactivation. Thus, estrogen
      upregulates eNOS gene expression in fetal PAECs through the activation of PAEC
      estrogen receptors. This mechanism may be responsible for pulmonary eNOS
      upregulation during late gestation, thereby optimizing the capacity for NO
      mediated pulmonary vasodilation at birth.

PMID- 9285638
TI  - High glucose concentrations increase endothelial cell permeability via activation
      of protein kinase C alpha.
AB  - Endothelial cell permeability is impaired in diabetes mellitus and may be
      increased by high extracellular glucose concentrations. High glucose activates
      protein kinase C (PKC), a family of kinases vital to intracellular signaling. We
      tested the hypothesis that high glucose concentration activates PKC in
      endothelial cells and leads to an increase in endothelial cell permeability via
      distinct PKC isoforms. Porcine aortic endothelial cells were used, and the PKC
      isoforms alpha, delta, epsilon, zeta, and theta were identified in these cells.
      Glucose caused a rapid dose-dependent increase in endothelial cell permeability,
      with an EC50 of 17.5 mmol/L. Phorbol 12-myristate 13-acetate (TPA) induced an
      increase in permeability very similar to that elicited by glucose. The effect of
      glucose and TPA was totally reversed by preincubating the cells with the PKC
      inhibitors staurosporine (10(-8) mol/L) and Goe 6976 (10(-8) mol/L).
      Downregulation of PKC by preincubation with TPA for 24 hours also abolished the
      effect of glucose and TPA on endothelial cell permeability. High glucose (20
      mmol/L) caused an increase in PKC activity at 2, 10, and 30 minutes. Cell
      fractionation and Western blot analysis showed a glucose-induced translocation of
      PKC alpha and PKC epsilon. Confocal microscopy confirmed the translocation and
      showed an association of PKC alpha and PKC epsilon with nuclear structures and
      the cell membrane. Specific antisense oligodesoxynucleotides (ODNs) against PKC
      alpha reduced the expression of the isoform, abolished the effects of glucose on
      endothelial cell permeability completely, and reduced the TPA effect
      significantly. In contrast, specific antisense ODNs against PKC epsilon had no
      effect on glucose-induced permeability and only a minor effect on the TPA-induced
      increase in permeability. We conclude that an increase in extracellular glucose
      leads to a rapid dose-dependent increase in endothelial cell permeability via the
      activiation of PKC and that this effect is mediated by the PKC isoform alpha.

PMID- 9285640
TI  - Modulation of Na+ current inactivation by stimulation of protein kinase C in
      cardiac cells.
AB  - Modulation of the inward Na+ current (I(Na)) by protein kinase C (PKC) was
      investigated by intracellular perfusion of a peptide corresponding to the
      catalytic subunit of PKC (PKCP). The effects of PKC activation independent of
      membrane-receptor pathways were studied in neonatal rat ventricular myocytes
      using whole-cell patch-clamp techniques. Perfusion with 2 nmol/L PKCP caused a
      depolarizing shift in steady state half-inactivation relative to control (-83.2+/
      1.3 versus -74.9+/-1.6 mV for control versus PKCP, respectively) without a change
      in current-voltage relationships or peak I(Na). The development of resting
      inactivation was slowed by PKCP (tau, 69.1+/-7.6 [control] versus 100.4+/-5.1
      ms). Open-channel inactivation, estimated by measuring I(Na) decay from peak
      current at test voltages between -10 and +30 mV was significantly slowed by PKCP.
      Recovery from inactivation was more rapid during PKCP perfusion, with a
      shortening of both the fast (tau(f)) and slow (tau(s)) components of tau (tau(f),
      38.5+/-7.0 [control] versus 14.2+/-4.7 ms; tau(s), 163.4+/-47.9 [control] versus
      51.3+/-9.2 ms). All of the effects of PKCP on I(Na) were antagonized by the PKC
      inhibitors chelerythrine chloride or staurosporine or by down-regulation of PKC
      using phorbol ester preincubation. We conclude that the actions of PKC on the Na+
      channel result in slowing the development of inactivation and accelerating
      reactivation, resulting in less resting inactivation.

PMID- 9285639
TI  - Mechanical transduction of nitric oxide synthesis in the beating heart.
AB  - NO alters contractile and relaxant properties of the heart. However, it is not
      known whether changes in ventricular loading conditions affect cardiac NO
      synthesis. To understand this potential contractile-relaxant autoregulatory
      mechanism, production of cardiac NO in response to mechanical stimuli was
      measured in vivo using a porphyrinic sensor placed in the left ventricular
      myocardium. The beating rabbit heart exhibited cyclic changes in [NO], peaking at
      2.7+/-0.1 micromol/L near the endocardium and 0.93+/-0.20 micromol/L in the
      midventricular myocardium (concentrations were 15+/-4% lower in the rat heart).
      In the present study, we demonstrate for the first time that increasing or
      decreasing ventricular preload in vivo is followed by parallel changes in [NO],
      which may represent a novel autoregulatory mechanism to adjust cardiac
      performance or perfusion on a beat-to-beat basis. To quantify the relationship
      between applied force and NO synthesis, intermittent compressive or distending
      forces applied to ex vivo nonbeating hearts were shown to cause bursts of NO
      synthesis, with peak [NO] linearly related to ventricular transmural pressure.
      Experiments in which denuding cardiac endothelial and endocardial cells abrogated
      the NO signal indicate that these cells transduce mechanical stimulation into NO
      production in the heart. Taken together, these studies may help explain load
      dependent relaxation, cardiac memory for mechanical events of preceding beats,
      diseases associated with myocardial distension, autoregulation of myocardial
      perfusion, and protection from thrombosis in the turbulent flow environment
      within the beating heart.

PMID- 9285641
TI  - Lysophosphatidylcholine modulates cardiac I(Na) via multiple protein kinase
      pathways.
AB  - Lysophosphatidylcholine (LPC) is a naturally occurring intracellular phospholipid
      metabolite that has been implicated in arrhythmogenesis during ischemia. LPC has
      been shown to affect the cardiac Na+ current (I(Na)), but the mechanism of
      modulation remains undescribed. Recently, low concentrations of LPC have been
      shown to activate protein kinase C (PKC) independent of the receptor-delineated
      pathway. The purposes of this study were to describe the effects of
      intracellularly introduced LPC on I(Na) and to determine if these effects were
      mediated by kinases. Modulation of I(Na) was studied in ventricular cells with
      LPC (1 nmol/L to 1 micromol/L) internally applied using whole-cell patch-clamp
      techniques. Intracellular LPC caused a dose-dependent depolarizing shift of
      steady state inactivation that was accompanied by a change in slope factor. The
      development of resting inactivation from closed states was delayed 40%, whereas
      the recovery from inactivation was significantly accelerated. These results were
      mimicked by another bioactive lipid, lysophosphatidylethanolamine, or by a
      peptide analogue of PKC, which is a potent stimulator of endogenous PKC activity.
      Maximal recruitable current was significantly increased by LPC but not by PKC
      activation. Some of the effects of LPC on I(Na) could be partially inhibited by
      the specific PKC inhibitor chelerythrine chloride or by downregulation of PKC
      with phorbol ester pretreatment. However, genistein, a specific tyrosine kinase
      inhibitor, completely inhibited all the modulation of I(Na) caused by LPC. These
      data suggest that LPC modulates I(Na) in cardiac myocytes by a pathway that
      involves both PKC-dependent and tyrosine kinase- dependent phosphorylation.

PMID- 9285642
TI  - Cross talk between angiotensin AT1 and alpha 1-adrenergic receptors: angiotensin
      II downregulates alpha 1a-adrenergic receptor subtype mRNA and density in
      neonatal rat cardiac myocytes.
AB  - Signaling mediated by the angiotensin (Ang) II and alpha1-adrenergic receptor
      (alpha1-AR) pathways is important for cardiovascular homeostasis. However, it is
      unknown whether Ang II has any direct effect on alpha1-AR expression and
      signaling in cardiac myocytes. In the present study, we determined alpha1-AR
      subtype mRNA levels by RNase protection; receptor density by competition binding
      with 5-methylurapidil; and alpha1-AR-mediated c-fos expression by Northern blot
      analysis. We found that Ang II had no effect on alpha1b- and alpha1d-AR mRNA
      levels but decreased the alpha1a-AR mRNA level in a time- and dose-dependent
      manner. The maximal effect occurred at 6 hours with 100 nmol/L Ang II (40.0+/
      8.2% reduction, n=4, P<.01). The decrease in alpha1a-AR mRNA level induced by Ang
      II is mediated by the Ang II AT1 receptor subtype and is associated with
      decreased stability of alpha1a-AR mRNA. Corresponding to the changes in the
      alpha1a-AR mRNA level, Ang II (100 nmol/L, 24 hours) reduced the density of high
      affinity sites for 5-methylurapidil (alpha1A-AR) by 29% (56.5+/-6.4 versus 79.0+/
      11.6 fmol/mg protein, n=4, P<.05). Alpha1-AR-stimulated c-fos induction, which
      could be blocked by 5-methylurapidil but not by chloroethylclonidine, was
      attenuated by Ang II preincubation (100 nmol/L, 24 hours). We conclude that there
      is previously undescribed cross talk between AT1 receptors and alpha1-ARs. Ang II
      selectively downregulates alpha1a-AR subtype mRNA and its corresponding receptor
      as well as alpha1a-AR-mediated expression of the immediate-early gene c-fos in
      cardiac myocytes.

PMID- 9285643
TI  - Ischemic preconditioning induces selective translocation of protein kinase C
      isoforms epsilon and eta in the heart of conscious rabbits without subcellular
      redistribution of total protein kinase C activity.
AB  - Considerable controversy surrounds the role of protein kinase C (PKC) in ischemic
      preconditioning (PC). Previous studies have used pharmacological agents and/or
      measured total myocardial PKC activity; however, no information is available
      regarding the effects of PC on individual isoforms in vivo. We performed a
      comprehensive evaluation (using Western immunoblotting) of the expression and
      subcellular distribution of all 11 currently known PKC isoforms in the heart of
      conscious rabbits subjected to four different ischemic PC protocols known to
      induce early and/or late PC (one, three, or six cycles of 4-minute coronary
      occlusion [4'O]/4-minute reperfusion [4'R]; four cycles of 5-minute occlusion
      [5'O]/10-minute reperfusion [10'R]). Ten PKC isoforms (alpha, beta1/beta2, gamma,
      delta, epsilon, zeta, eta, iota, lambda, and mu) were found to be expressed in
      the rabbit heart. Quantitative immunoblotting demonstrated that as a subgroup,
      conventional PKCs (cPKCs) are more abundant than novel PKCs (nPKCs) (1445 versus
      313 pg PKC/microg tissue protein, respectively) and that PKC alpha is the
      predominant isoform among the cPKCs (alpha, beta1, beta2, and gamma),
      representing 51% of this subgroup, and PKC epsilon is the most abundant among the
      nPKCs (delta, epsilon, zeta, and eta), accounting for 62% of this subgroup. None
      of the ischemic PC protocols examined caused appreciable changes in total PKC
      activity, in the subcellular distribution of total PKC activity, or in the
      subcellular distribution of PKC isoforms alpha, beta1/beta2, gamma, delta, zeta,
      iota, lambda, and mu. In contrast, all PC protocols caused significant
      translocation of PKC epsilon and PKC eta isoforms from the cytosolic to the
      particulate fraction. The particulate fraction of PKC epsilon increased in a dose
      dependent fashion with the number of occlusion/reperfusion cycles performed, from
      35+/-2% in the control group to 43+/-2% after one 4'O/5-minute reperfusion (5'R)
      cycle (P<.05), 52+/-2% after three cycles (P<.05 versus one cycle), and 66+/-3%
      after six cycles (P<.05 versus three cycles). The particulate fraction of PKC
      epsilon also increased, after four 5'O/10'R cycles, to 50+/-3% (P<.05 versus
      control). In contrast to PKC epsilon, the translocation of PKC eta was
      independent of the number of occlusion/reperfusion cycles performed. The
      particulate fraction of PKC eta increased from 67+/-3% in the control group to
      84+/-2% after one 4'O/5'R cycle (P<.05), 84+/-2% after three 4'O/4'R cycles
      (P<.05), 86+/-3% after six 4'O/4'R cycles (P<.05), and 83+/-2% after four
      5'O/10'R cycles (P<.05). When expressed as a percentage of control values, the
      increases in the particulate fraction of isoform epsilon were greater than those
      of isoform eta. The effects of 4'O without reperfusion were similar to those of
      one cycle of 4'O/5'R, indicating that 5'R did not attenuate isoform
      translocation. This is the first study to demonstrate PKC translocation after
      ischemic PC in vivo. The results indicate that in the conscious rabbit, ischemic
      PC causes selective translocation of the epsilon and eta isoforms without
      demonstrable changes in total myocardial PKC activity, implying that measurements
      of total PKC activity are not sufficiently sensitive to detect the involvement of
      PKC in PC. The results are consistent with the concept that the epsilon and eta
      isozymes play an important role in the genesis of ischemic PC in the conscious
      rabbit.

PMID- 9285645
TI  - Expression pattern of connexin gene products at the early developmental stages of
      the mouse cardiovascular system.
AB  - The synchronized contraction of myocytes in cardiac muscle requires the
      structural and functional integrity of the gap junctions present between these
      cells. Gap junctions are clusters of intercellular channels formed by
      transmembrane proteins of the connexin (Cx) family. Products of several Cx genes
      have been identified in the mammalian heart (eg, Cx45, Cx43, Cx40, and Cx37), and
      their expression was shown to be regulated during the development of the
      myocardium. Cx43, Cx40, and Cx45 are components of myocyte gap junctions, and it
      has also been demonstrated that Cx40 was expressed in the endothelial cells of
      the blood vessels. The aim of the present work was to investigate the expression
      and regulation of Cx40, Cx43, and Cx37 during the early stages of mouse heart
      maturation, between 8.5 days post coitum (dpc), when the first rhythmic
      contractions appear, and 14.5 dpc, when the four-chambered heart is almost
      completed. At 8.5 dpc, only the reverse-transcriptase polymerase chain reaction
      technique has allowed identification of Cx43, Cx40, and Cx37 gene transcripts in
      mouse heart, suggesting a very low activity level of these genes. From 9.5 dpc,
      all three transcripts became detectable in whole-mount in situ-hybridized
      embryos, and the most obvious result was the labeling of the vascular system with
      Cx40 and Cx37 anti-sense riboprobes. Cx40 and Cx37 gene products (transcript
      and/or protein) were demonstrated to be expressed in the vascular endothelial
      cells at all stages examined. By contrast, only Cx37 gene products were found in
      the endothelial cells of the endocardium. In heart, Cx37 was expressed
      exclusively in these cells, which rules out any direct involvement of this Cx in
      the propagation of electrical activity between myocytes and the synchronization
      of contractions. Between 9.5 and 11.5 dpc, Cx40 gene activation in myocytes was
      demonstrated to proceed according to a caudorostral gradient involving first the
      primitive atrium and the common ventricular chamber (9.5 dpc) and then the right
      ventricle (11.5 dpc). During this period of heart morphogenesis, there is clearly
      a temporary and asymmetrical regionalization of the Cx40 gene expression that is
      superimposed on the functional regionalization. In addition, comparison of Cx40
      and Cx43 distribution at the above developmental stages has shown that these Cxs
      have overlapping (left ventricle) or complementary (atrial tissue and right
      ventricle) expression patterns.

PMID- 9285644
TI  - Ischemic preconditioning prevents the impairment of hypoxic coronary
      vasodilatation caused by ischemia/reperfusion: role of adenosine A1/A3 and
      bradykinin B2 receptor activation.
AB  - We previously reported that hypoxic coronary vasodilatation (HCVD) is initiated
      by endothelial NO and sustained by adenosine. Prolonged ischemia/reperfusion
      impairs endothelium-dependent coronary vasodilatation, whereas transient ischemia
      (ie, preconditioning) protects the myocardium from subsequent ischemic events.
      Accordingly, we assessed whether prolonged ischemia/reperfusion impairs HCVD and
      whether preconditioning prevents this dysfunction. HCVD, elicited in isolated
      guinea pig hearts by a 1-minute exposure to 100% N2, consisted of an
      approximately 70% increase in coronary flow associated with enhanced
      nitrite/nitrate and adenosine overflow (+40% and 5-fold, respectively). After 30
      minute global ischemia and 20-minute reperfusion, HCVD was decreased by
      approximately 60%, and the increases in nitrite/nitrate and adenosine overflow
      were abolished. Preconditioning (ie, three cycles of 5-minute global ischemia+5
      minute reperfusion) prevented the impairment of HCVD and fully restored the
      increase in nitrite/nitrate overflow, but not that of adenosine. The protective
      effect of preconditioning was mimicked by perfusion with the adenosine A1
      receptor agonist N6-cyclopentyladenosine and prevented by the A1 receptor
      antagonist N-0861. In addition, the A3 receptor agonist N6-(3
      iodobenzyl)adenosine-5'-N-methyl-carboxamide had a similar protective effect. The
      bradykinin B2 receptor antagonist HOE 140 abolished the protective effect of
      preconditioning, whereas the NO synthase inhibitor N(omega)-methyl-L-arginine and
      the cycloxygenase inhibitor indomethacin did not. Our data indicate that
      preconditioning restores HCVD by a process that is triggered by activation of
      adenosine A1/A3 and bradykinin B2 receptors. The action of bradykinin is
      independent of NO and prostacyclin production. Once restored by preconditioning,
      HCVD is mediated by NO but no longer sustained by adenosine.

PMID- 9285646
TI  - Left ventricular norepinephrine and epinephrine kinetics at birth in lambs.
AB  - Little is known about the changes in the left ventricular (LV) kinetics of the
      catecholamines norepinephrine and epinephrine occurring at birth and their
      relationship to perinatal alterations in LV function and whole-body catecholamine
      kinetics. To address this issue, whole-body and LV catecholamine kinetics
      (radiotracer dilution methodology) and fetal LV output and myocardial blood flow
      (radioactive microspheres) were measured in chronically instrumented near-term
      fetuses and in the same animals 1 and 4 hours after birth. Between fetal and 1
      hour lambs, LV external work increased 115% (P<.005); carotid arterial plasma
      norepinephrine concentration, 148% (P<.01); carotid arterial plasma epinephrine
      concentration, 546% (P<.005); LV norepinephrine spillover, a measure of LV
      sympathetic activity, 4.1-fold (P<.005); LV epinephrine spillover, 3-fold
      (P<.05); total-body spillover of norepinephrine, 52% (P<.025); and total-body
      spillover of epinephrine, 460% (P<.005). Arterial catecholamine concentrations
      and total-body catecholamine spillovers were unchanged between 1- and 4-hour
      lambs, but LV external work fell (P<.05) to a level still 77% greater than in
      fetal lambs (P<.005); LV norepinephrine spillover returned to near-fetal levels,
      and LV epinephrine spillover became undetectable. These results suggest that (1)
      a transient increase in LV sympathetic activity occurs at birth and may
      contribute to the immediate postnatal augmentation of LV performance, (2) organ
      differences in the pattern of sympathetic activation occur at birth, and (3)
      birth-related increases in LV sympathetic activity are accompanied by release of
      epinephrine from the heart.

PMID- 9285647
TI  - Regulation of matrix metalloproteinase expression in human vascular smooth muscle
      cells by T lymphocytes: a role for CD40 signaling in plaque rupture?
AB  - Physical disruption of an atheromatous lesion often underlies acute coronary
      syndromes. Matrix-degrading enzymes, eg, matrix metalloproteinases (MMPs), may
      cause loss in mechanical integrity of plaque tissue that favors rupture. T
      lymphocytes accumulate at sites where atheromata rupture, but the mechanisms by
      which these immune cells may contribute to plaque destabilization are unknown.
      This study tested the hypothesis that the T-lymphocyte surface molecule CD40
      ligand (CD40L), recently localized in atherosclerotic plaques, regulates the
      expression of MMPs in human vascular smooth muscle cells (SMCs), the most
      numerous cell type in arteries. We report here that stimulated human T
      lymphocytes induced the expression of the matrix-degrading enzymes, ie,
      interstitial collagenase (MMP-1), stromelysin (MMP-3), gelatinase B (MMP-9), and
      activated gelatinase A (MMP-2), in human vascular SMCs by cell contact via CD40
      ligation, as demonstrated by Western blot analysis, zymography, and antibody
      neutralization. Recombinant human CD40L (rCD40L) induced de novo synthesis of MMP
      1, MMP-3, and MMP-9 on vascular SMCs and stimulated the expression of these
      enzymes to a greater extent than did maximally effective concentrations of tumor
      necrosis factor-alpha or interleukin-1beta, established agonists of MMP
      expression. Interferon gamma, another T-lymphocyte- derived cytokine, inhibited
      the induction of MMPs by rCD40L. Immunohistochemical analysis of human coronary
      atheromata colocalized MMP-1 and MMP-3 with CD40-positive SMCs. These results
      demonstrated that CD40 ligand, expressed on T lymphocytes, promoted the
      expression of matrix-degrading enzymes in vascular SMCs and thus established a
      new pathway of immune-modulated destabilization in human atheromata.

PMID- 9285648
TI  - Diagnostic criteria and management of subacute ventricular free wall rupture
      complicating acute myocardial infarction.
AB  - In this prospective study we evaluated the value of the main diagnostic criteria
      for postinfarction subacute rupture of the ventricular free wall. Two-dimensional
      echocardiograms and recordings of right atrial pressure and waveform were
      immediately obtained in every patient exhibiting rapid clinical and/or
      hemodynamic compromise in the acute infarction setting. The same protocol was
      applied to patients referred from other hospitals for suspected myocardial
      rupture. In 28 cases a subacute free wall rupture was identified. In most of the
      patients the diagnosis was based on the demonstration of hemopericardium and
      cardiac tamponade by echocardiography, cardiac catheterization and, occasionally,
      by pericardiocentesis. In 2 instances, the identification of intrapericardial
      echo densities suggesting clots, in the absence of cardiac tamponade, allowed a
      diagnosis of subacute rupture. Direct, but indistinct visualization of myocardial
      rupture was obtained in 4 cases. Among the 28 patients with this complication, 4
      died while awaiting surgery and 24 underwent surgical repair (mortality rate
      33%). Long-term outcome of survivors was favorable. Various myocardial lesions
      underlie postinfarction subacute free wall rupture. Clinical presentation varied
      widely. The diagnosis was based, usually but not always, on the association of
      hemopericardium and signs of cardiac tamponade. An organized approach to
      management of this complication of acute myocardial infarction was suggested.

PMID- 9285649
TI  - Prognostic value of slow resolution of ST-segment elevation following successful
      direct percutaneous transluminal coronary angioplasty for recovery of left
      ventricular function.
AB  - Our objective was to investigate the significance of the slow resolution of ST
      segment elevation following a successful direct percutaneous transluminal
      coronary angioplasty (PTCA). ST-segment elevations were calculated from
      electrocardiograms recorded before PTCA and 1 hour after reperfusion. Forty-nine
      patients experiencing their first anterior acute myocardial infarction and who
      had undergone direct PTCA were classified into 3 groups: 17 patients with rapid
      ST resolution (group I), 23 patients with persistent ST elevation (group II), and
      9 patients with ST reelevation (group III). Left ventricular function was
      evaluated by using single-plane cineventriculography performed in the acute
      stage, at discharge, and 4 months later. Peak creatine kinase activity was
      significantly increased: group III (4,046 +/- 634 IU), group II (3,336 +/- 772
      IU), and group I (2,410 +/- 994 IU); p <0.05. Ejection fraction and regional wall
      motion in the acute stage were identical in each group. However, they were
      significantly higher in group I (67 +/- 6%, -1.01 +/- 0.30), followed by group II
      (56 +/- 6%, -1.90 +/- 0.41) and group III (38 +/- 7%, -2.79 +/- 0.46); p <0.01 4
      months later. Multiple regression analysis revealed that the ST resolution was
      the only significant variable that indicated the recovery of regional wall
      motion. A good linear correlation was documented between the ST resolution and
      the recovery of regional wall motion. We concluded that a slow ST resolution
      after successful direct PTCA is a negative predictor of recovery of left
      ventricular function, especially when ST reelevation is evident.

PMID- 9285650
TI  - A new predictor of restenosis after successful percutaneous transluminal coronary
      angioplasty in patients with multivessel coronary artery disease.
AB  - With the goal of improving prediction of restenosis after percutaneous
      transluminal coronary angioplasty (PTCA) for multivessel coronary artery disease
      (CAD), we evaluated the usefulness of serial exercise treadmill tests. We
      previously reported that an increase in the deltaST/delta heart rate (HR) index
      at follow-up over the value obtained several days after PTCA was useful for
      detecting restenosis following PTCA for 1-vessel CAD. In that report, comparison
      of the deltaST/deltaHR index was made based on measurements from the lead
      disclosing the greatest ST displacement before PTCA. This method was not
      applicable to patients with multivessel CAD. Seventy-eight patients with
      multivessel CAD before and several days after PTCA and just before follow-up
      performed exercise treadmill tests. Simple HR-adjusted indexes of ST-segment
      depression during exercise (deltaST/deltaHR index) and the sum of the
      deltaST/deltaHR index in leads II, III, aVF, V4, V5, and V6 (sigma
      deltaST/deltaHR index) were determined. We compared the predictive power of an
      increase in sigma deltaST/deltaHR index at follow-up with that of a positive
      exercise treadmill test and a positive thallium scintigram for restenosis. At
      follow-up, 37 of the 78 patients showed restenosis. The sigma deltaST/deltaHR
      index had increased in 30 of these 37 patients (81%), and in 12 of the 41
      patients (29%) without restenosis. An increase in sigma deltaST/deltaHR index had
      a significantly higher sensitivity than the other methods and a significantly
      higher specificity than a positive exercise treadmill test.

PMID- 9285651
TI  - Red wine, white wine, liquor, beer, and risk for coronary artery disease
      hospitalization.
AB  - International comparison data suggest that wine may be more protective against
      coronary artery disease than beer or liquor. There are potentially protective
      antioxidants in wine, especially red wine. However, prospective population
      studies suggest that each beverage type may reduce coronary risk. The role of
      alcoholic beverage choice in coronary risk remains unresolved. We performed a
      prospective study of coronary disease hospitalizations among 128,934 adult
      members of a Northern California prepaid comprehensive health care program.
      Alcohol data were supplied at health examinations. Using Cox proportional-hazards
      models with 9 covariates, analyses were performed of the roles of each major
      beverage type (wine, beer, and liquor) and of drinking only table wine (red,
      white, or both). Generally, coronary risk traits were most favorable for wine
      drinkers and least favorable for liquor drinkers. Among 3,931 persons
      hospitalized for coronary disease, total alcohol drinking was inversely related
      to risk in both sexes. Uncontrolled for total alcohol, each beverage type showed
      evidence for coronary protection, weakest for liquor and strongest for beer in
      men and wine in women. Controlled for total alcohol, these relations were much
      reduced, and lost statistical significance except for beer in men and both red
      and white wine (combined) in all persons. We conclude that (1) drinking ethyl
      alcohol apparently protects against coronary disease, and (2) there may be minor
      additional benefits associated with drinking both beer and wine, but not
      especially red wine.

PMID- 9285653
TI  - Incremental prognostic value of adenosine stress myocardial perfusion single
      photon emission computed tomography and impact on subsequent management in
      patients with or suspected of having myocardial ischemia.
AB  - We examined 1,159 consecutive patients who underwent adenosine stress dual
      isotope single-photon emission computed tomography (SPECT) and had follow-up
      performed at a mean of 27.5 +/- 9.1 months (94% complete) for hard events
      (cardiac death and myocardial infarction) and referral to cardiac catheterization
      after nuclear testing. During follow-up, 120 hard events occurred (11.0% hard
      event rate; 72 cardiac deaths [6.7% cardiac death rate] and 57 myocardial
      infarctions [5.3% myocardial infarction rate]). Cox proportional hazards analysis
      revealed that nuclear testing added incremental value after adjusting for
      clinical and historical variables (global chi-square increased 13 to 98 for
      cardiac death as the end point, global chi-square increased 19 to 105 for hard
      events as the end point; p <0.0001 for both). Kaplan-Meier analysis demonstrated
      that after clinical risk stratification of the patient population, the results of
      nuclear testing were further able to significantly stratify both low- and
      intermediate- to high-risk patients. Patients with both normal and mildly
      abnormal scans were at low risk of cardiac death (<1% cardiac death per year of
      follow-up) and the risk of events increased significantly with worsening scan
      result. Multivariable analysis revealed that the only predictor of referral to
      catheterization was the extent and severity of reversible defect present on the
      scan. Referral rates to early catheterization were very low in patients with
      normal scans and increased significantly as a function of worsening scan results.
      In patients who underwent myocardial perfusion SPECT using adenosine stress, the
      results of nuclear testing yielded incremental prognostic information and
      clinically relevant risk stratification. Referring physicians predominantly
      utilized nuclear information when referring patients to catheterization after
      nuclear testing and do so at rates comparable with those after exercise SPECT
      despite the higher risk of events in patients undergoing pharmacologic stress.

PMID- 9285652
TI  - Effect of morning versus evening dosing of diltiazem on myocardial ischemia
      detected by ambulatory electrocardiographic monitoring in chronic stable angina
      pectoris. Dilacor XR Ambulatory Ischemia Study Group.
AB  - Myocardial ischemia occurs frequently during daily life and has a circadian
      pattern similar to that reported for myocardial infarction and sudden death.
      Because of the increased risk of myocardial ischemia in the morning hours, it has
      been suggested that the administration of anti-ischemic medication before bedtime
      may be more effective than the traditional morning dosing. This randomized,
      double-blind, placebo-controlled, crossover study evaluated the effects of 480
      mg/day diltiazem (given either in the A.M. or the P.M.) on myocardial ischemia
      using ambulatory electrocardiographic monitoring in 68 patients with chronic
      stable angina and > or = 2 minutes of ischemia per 48 hours. During treatment
      with diltiazem, the duration and number of myocardial ischemic episodes were
      reduced by 45% (94 to 52 minutes, p <0.004) and by 40% (4.5 to 2.7 episodes, p
      <0.003), respectively. The duration and number of myocardial ischemic episodes
      during daytime (6 A.M. to 6 P.M.) hours were also reduced by 52% (74 to 36
      minutes, p <0.002) and by 48% (3.1 to 1.6 episodes, p <0.001), respectively.
      There was no significant difference between A.M. and P.M. dosing. Morning
      ischemia (6 A.M. to noon), considered separately from daytime ischemia, was also
      significantly reduced by both A.M. and P.M. dosing regimens, with no difference
      between the regimens. The results of this study showed that both A.M. and P.M.
      dosing of long-acting diltiazem were equally effective in suppressing episodes of
      ambulatory myocardial ischemia at all times.

PMID- 9285654
TI  - Correlation of thallium uptake with left ventricular wall thickness by cine
      magnetic resonance imaging in patients with acute and healed myocardial infarcts.
AB  - Myocardial infarction (MI) is characterized by cellular necrosis which undergoes
      fibrotic transformation over time. Cine magnetic resonance imaging (MRI) offers
      high-resolution 3-dimensional images of the left ventricular myocardium, allowing
      sampling of the myocardial wall thickness over the entire left ventricle.
      Tomographic (single-photon emission computed tomography [SPECT]) thallium images
      also provide 3-dimensional information on the location and level of thallium
      uptake, which has been shown to correlate with myocardial viability. The purposes
      of this study were: (1) to examine the relation between both end-diastolic and
      end-systolic wall thickness and normalized thallium-201 uptake over the left
      ventricle in a group of patients with MI, (2) to examine the relation between
      regional wall thickening and normalized thallium uptake, and (3) to examine the
      relation between thallium uptake and wall thickness both early and late after
      infarction. Twenty-four patients with MI underwent stress, redistribution, and
      reinjection thallium SPECT imaging and cine MRI within several days. Seventeen
      patients underwent imaging late after infarction and 7 underwent imaging early
      after infarction. Normalized thallium activity was correlated with MRI wall
      thicknesses at both end-diastole and end-systole for 18 segments for each
      ventricle. In addition, end-diastolic and end-systolic wall thicknesses were
      grouped by their corresponding thallium activity levels into percentiles. End
      systolic wall thickness correlated significantly with normalized thallium uptake
      in 14 of 18 segments, end-diastolic wall thickness in only 4 of 18 segments, and
      wall thickening in only 3 of 18 segments. Mean values for end-diastolic and end
      systolic wall thicknesses corresponding to severely reduced (<50%) normalized
      thallium activity were 9.9 +/- 1.1 and 8.5 +/- 0.6, respectively. Using receiver
      operating curve analysis, end-systolic wall performed as a better diagnostic
      parameter than end-diastolic wall for identifying severely reduced thallium
      activity levels. For all levels of thallium activity, end-diastolic wall
      thicknesses were all thinner late versus early after MI, whereas end-systolic
      wall thickness was thinner only in the segments corresponding to severely reduced
      thallium activity. Based on these results, end-systolic wall thickness is the
      best noninvasive anatomic parameter of myocardial scar.

PMID- 9285655
TI  - Incidence and natural history of left ventricular thrombus following anterior
      wall acute myocardial infarction.
AB  - Previous studies have reported left ventricular (LV) thrombus in 20% to 56% of
      patients after anterior wall acute myocardial infarction (AMI). The Healing and
      Early Afterload Reducing Therapy (HEART) study was a prospective study comparing
      effects of early (24 hours) or delayed (14 days) initiation of ramipril, an
      angiotensin-converting enzyme inhibitor, on LV function after anterior wall AMI.
      This ancillary study assessed prevalence of LV thrombus. Two-dimensional
      echocardiography was performed on days 1, 14, and 90 after myocardial infarction.
      The cohort consisted of 309 patients. Q-wave anterior wall AMI occurred in 78%;
      87% received reperfusion therapy. The prevalence of LV thrombus was 2 of 309
      (0.6%) at day 1, 11 of 295 (3.7%) at day 14, and 7 of 283 (2.5%) at day 90. One
      patient had thrombus at 2 examinations. The day 1 echocardiogram was not
      correlated with thrombus development. LV size increased more in patients with
      thrombus than in those without thrombus. Patients with thrombus had more wall
      motion abnormality after day 1 than patients without thrombus (p = 0.03). Thus,
      the current prevalence of LV thrombus in anterior wall AMI is lower than
      previously reported, possibly due to changes in AMI management. Preservation of
      LV function is likely to be an important mechanism. Most thrombi are seen by 2
      weeks after AMI. Resolution documented by echocardiography is frequent.

PMID- 9285656
TI  - Comparison of degrees of left ventricular dilation within three hours and up to
      six days after onset of first acute myocardial infarction.
AB  - Following an acute myocardial infarction (AMI) there is immediate deterioration
      of contractility in the infarcted left ventricular (LV) wall. This can be
      followed by regional dilation (expansion) as well as global remodeling. We
      examined 35 consecutive patients--with no history of myocardial ischemia--who
      were admitted to hospital within 3 hours after initial symptoms and with ST
      segment changes on an electrocardiogram consistent with transmural ischemia.
      Echocardiography was performed at admission, and at 6 hours, 12 hours, 24 hours,
      3 days, and 6 days after onset of the AMI. Within 3 hours after onset of symptoms
      an increase in both end-diastolic volume index (EDVI) and end-systolic volume
      index (ESVI) was found in both anterior and inferior infarcts when compared with
      healthy controls (mean +/- SD EDVI: 99 +/- 13 ml/m2 [anterior], 69 +/- 17 ml/m2
      [inferior], 51 +/- 15 ml/m2 [controls], p < or = 0.00001; ESVI: 62 +/- 12 ml/m2
      [anterior], 38 +/- 11 ml/m2 [inferior], 17 +/- 6 ml/m2 [controls], p < or =
      0.00001). At all points in time, volumes were larger in anterior infarcts than in
      inferior infarcts (p < 0.05). The volumes did not change during the 6 days (p >
      0.1). Thus, major LV dilation is present within 3 hours after onset of symptoms
      of first AMI. The dilation is more pronounced in anterior versus inferior
      infarcts. From 3 hours until day 6 no further changes in LV volumes occurred.

PMID- 9285658
TI  - Acute hemodynamic effects of intravenous ibutilide in patients with or without
      reduced left ventricular function.
AB  - Many antiarrhythmic agents have adverse hemodynamic effects which limit their use
      in patients with impaired ventricular function or during tachyarrhythmias.
      Ibutilide is an intravenous, selective class III antiarrhythmic agent that is
      effective for conversion of atrial fibrillation or flutter. This multicenter,
      randomized, placebo-controlled, dose-ranging study evaluated the effects of
      intravenous ibutilide on hemodynamic parameters during invasive monitoring in 47
      patients with or without reduced left ventricular ejection fraction (LVEF) > 35%
      or < or = 35%. Patients received either placebo or ibutilide as a 10-minute
      loading and a 30-minute maintenance infusion using 1 of the following dosing
      regimens: placebo then placebo (n = 12); 0.01 then 0.002 mg/kg (n = 12); 0.02
      then 0.004 mg/kg (n = 12); or 0.03 then 0.006 mg/kg (n = 11). Ibutilide
      significantly increased QT and QTc intervals in a dose-related manner with mean
      increases ranging from 51 to 99 ms, but did not alter the PR interval or QRS
      duration. During ibutilide infusion, a few small but statistically significant
      changes from baseline in several hemodynamic variables were present. However, the
      changes in cardiac output, pulmonary artery or capillary wedge pressures, blood
      pressure, or heart rate in patients receiving ibutilide were not significantly
      different from the changes in patients receiving placebo. Thus, ibutilide did not
      cause clinically important adverse hemodynamic effects, even in patients with
      depressed ventricular function. One patient developed 2 episodes of nonsustained
      torsades de pointes during ibutilide. These results demonstrate that with careful
      monitoring for proarrhythmia, ibutilide can be used safely from a hemodynamic
      standpoint in the acute treatment of arrhythmias, even in patients with reduced
      ventricular function.

PMID- 9285657
TI  - Comparison of clinical characteristics and frequency of implantable defibrillator
      use between randomized patients in the Antiarrhythmics Vs Implantable
      Defibrillators (AVID) trial and nonrandomized registry patients.
AB  - In the Antiarrhythmics Vs Implantable Defibrillators (AVID) trial, all patients
      who meet the study entry criteria are followed in a registry. During the period
      between June 1993 and June 1995, of 1,117 patients who were enrolled in the
      registry and met the study entry criteria, 476 were randomized to receive either
      implantable cardioverter-defibrillators (ICDs) or drug therapy (amiodarone or
      sotalol), and 641 patients were not randomized for a variety of reasons
      including: patient refusal (42%); physician refusal (43%); concerns about ability
      to maintain follow-up over several years (10%), and others (6%). There were no
      significant differences between the 476 randomized and 641 nonrandomized patients
      with regard to clinical characteristics, left ventricular function, history of
      congestive heart failure, medical history, and previous cardiac procedures
      performed before the index event, except that randomized patients were slightly
      older (65 vs 62 years) and had a slightly higher prevalence of coronary artery
      disease and previous myocardial infarction. The index event and location of the
      index event were not significantly different between the 2 groups. Although 14%
      of registry patients received neither ICD nor antiarrhythmic drug therapy, ICDs
      were no more frequently used in the registry patient than antiarrhythmic drugs
      (45% for ICD vs 42% for drugs). Thus, randomized AVID patients have very similar
      clinical characteristics, cardiac history, and presenting arrhythmias as to
      nonrandomized eligible patients. Therefore, the results of the AVID trial may be
      generalized for all patients with AVID-eligible arrhythmias.

PMID- 9285659
TI  - Pilot study and protocol of the Canadian Trial of Atrial Fibrillation (CTAF).
AB  - Antiarrhythmic drug prophylaxis in patients with atrial fibrillation (AF) is
      associated with a high incidence of arrhythmic recurrence. Uncontrolled studies
      have suggested that low-dose amiodarone may be superior in terms of efficacy to
      other antiarrhythmic drugs while having an acceptable side effect profile. The
      Canadian Trial of Atrial Fibrillation (CTAF) is a 25-center study sponsored by
      the Medical Research Council of Canada to determine the best treatment strategy
      to maintain sinus rhythm in patients with persistent or paroxysmal AF.
      Recruitment began in November 1996 and will continue for 1.5 years. Patients are
      randomized to receive either low-dose amiodarone or conventional antiarrhythmic
      drug therapy. Patients assigned to the amiodarone group will receive an oral
      loading regimen of 10 mg/kg/day during a minimum 14-day period. Patients assigned
      to conventional antiarrhythmic therapy will receive 1 of 2 agents commonly used
      in AF prophylaxis: sotalol or propafenone. Drug selection and loading, and
      electrical cardioversion, if necessary, will be performed within 21 days of
      randomization. The long-term maintenance dose of amiodarone is 200 mg/day. We
      have planned a minimum follow-up period of 1 year. The primary end point is the
      time to the first relapse of AF. Data will be analyzed on an intention-to-treat
      basis. Secondary outcomes are medication toxicity, mortality, major clinical
      events, costs of each approach, and quality of life. For the purpose of sample
      size calculations, it is anticipated that recurrence of AF at 1 year will occur
      in 50% of patients on conventional treatment compared with 35% in those receiving
      amiodarone. In order to have an 80% power and a 2-tailed type I error of 0.05,
      assuming a 15% loss to follow-up rate, a total sample size of 400 patients will
      be required. A pilot study done at the Montreal Heart Institute has shown that
      the research protocol is feasible.

PMID- 9285660
TI  - Effects of controlled-onset extended-release verapamil on nocturnal blood
      pressure (dippers versus nondippers). COER-Verapamil Study Group.
AB  - Approximately 1 in 4 patients with systemic hypertension have a 24-hour blood
      pressure (BP) profile characterized by a blunted or absent nocturnal decline in
      pressure. We evaluated the effects of a chronotherapeutic delivery system of
      controlled-onset extended-release (COER) verapamil hydrochloride and placebo in
      257 hypertensive patients according to their circadian BP pattern in an 8-week
      prospective, multicenter, randomized, and double-blind clinical trial. Patients
      were stratified into 193 dippers (>10% decline in BP during the period of 10 P.M.
      to 5 A.M. compared with the hours of 5 A.M. to 10 P.M.) and 64 nondippers (<10%
      decline in BP during nighttime). During daytime, placebo-subtracted BP was
      similarly decreased in dippers and nondippers by COER verapamil. During
      nighttime, the placebo increased nocturnal BP in dippers (baseline nocturnal BP,
      133/78 mm Hg) by 3/3 +/- 2/2 mm Hg and reduced BP by -5/-3 +/- 2/2 mm Hg in
      nondippers (baseline nocturnal BP, 152/94 mm Hg) (p = NS between groups). After
      controlling for age, gender, ethnicity, and the regression to the mean observed
      on placebo for all doses, COER verapamil reduced nocturnal BP more in nondippers
      than dippers -5.8/-2.4 mm Hg, p <0.0001 for systolic BP and p = 0.09 for
      diastolic BP). Additionally, a significant dose-related reduction in systolic and
      diastolic nocturnal BP (r = 0.56, p <0.0001 for systolic BP and r = 0.62, p
      <0.0001 for diastolic BP) was observed with COER verapamil after controlling for
      baseline covariates. These data demonstrate that nocturnal BP is decreased by a
      greater extent in nondipper hypertensives than in dipper hypertensives following
      treatment with COER verapamil HCL.

PMID- 9285661
TI  - Gender-associated differences in left ventricular geometry in patients with
      aortic valve disease and effect of distinct overload subsets.
AB  - Gender-associated differences may play an important role in the way the left
      ventricle adapts to overload. The purpose of this study is to evaluate left
      ventricular (LV) geometry in patients referred for aortic valve replacement with
      distinct overload subsets. The echocardiograms of 128 patients with isolated
      aortic stenosis (n = 44), mixed aortic valvular disease (n = 51), and pure aortic
      regurgitation (n = 33) before aortic valve replacement were evaluated. Women had
      better LV function as measured by ejection fraction (58% vs 52%; p = 0.01) and
      were slightly older (67 vs 62 years, p = 0.11). LV dimensions and volumes indexes
      were distinctively smaller in women irrespective of the subgroups analyzed. Men
      had larger LV mass and LV mass index, but women had higher LV mass/volume ratio.
      Gender-related differences in LV mass/volume ratio were most prominent in the
      aortic stenosis patients (3.1 g/ml for women vs 2.3 g/ml for men; p = 0.001),
      tended to decrease in mixed aortic disease (2.3 g/ml for women vs 1.8 g/ml for
      men; p = 0.01), and were not present in patients with pure aortic regurgitation
      (1.7 g/ml for women vs 1.7 g/ml for men; p = 0.83). Multivariate analysis showed
      that gender was independently associated with LV mass/volume ratios, after
      adjusting for the severity of the valvular lesion, age, LV function, and
      concomitant coronary bypass graft surgery. Thus, in a selected population of
      patients with severe aortic valvular disease, there were significant gender
      related differences in LV geometry, mainly in patients exposed to chronic
      pressure overload.

PMID- 9285662
TI  - Comparison of alcoholic cardiomyopathy in women versus men.
AB  - To compare the prevalence and cardiac status of male and female alcoholics with
      alcoholic cardiomyopathy during a 5-year period, all chronic alcoholics with
      dilated cardiomyopathy who had clinical symptoms of heart failure were included.
      Alcoholic cardiomyopathy was diagnosed in 10 chronic alcoholic women and in 26
      men; the prevalence of alcoholic cardiomyopathy was similar in both sexes. No
      significant differences were observed in age, nutritional parameters, and
      clinical and radiologic data of heart failure between the 2 groups. Alcoholic
      women reported a significantly lower daily dose of ethanol (p = 0.002), a shorter
      duration of alcoholism (p = 0.017), and a lower total lifetime dose of ethanol
      consumption (p = 0.001), and had a lower New York Heart Association functional
      class than men. Women also had lesser ventricular dysfunction than men. In a
      multivariate analysis, left ventricular systolic dysfunction was related to the
      total lifetime dose of ethanol consumption (p <0.04), but not to gender. Finally,
      when patients were matched for left ventricular ejection fraction, women had
      consumed a lower total lifetime dose of ethanol than men (p <0.001). The
      prevalence of alcoholic women with dilated cardiomyopathy was found to be similar
      to that of alcoholic men, although women required a lower total lifetime dose of
      ethanol to develop the disease.

PMID- 9285663
TI  - Right ventricular dilation in primary amyloidosis: an independent predictor of
      survival.
AB  - This study was designed to characterize the geometry and function of the right
      ventricle and its prognostic significance in patients with primary (AL) cardiac
      amyloidosis. AL amyloidosis is an infiltrative systemic disease that can result
      in thickening of heart structures and rapidly progressive congestive heart
      failure due to restrictive ventricular physiology and eventual systolic
      dysfunction. Thirty-seven patients with AL amyloid heart involvement and 20
      normal control subjects were evaluated using 2-dimensional and Doppler
      echocardiography. Based on the ratio of left-to-right end-diastolic ventricular
      chamber areas, patients were classified into 2 groups: 25 patients with
      disproportionate right ventricular (RV) dilation (left ventricular to RV ratio <
      or = 2) and 12 with a ventricular area ratio > 2. Patients with a relatively
      dilated right ventricle (ratio < or = 2) had a shorter median survival (4 months)
      compared with patients with an area ratio > 2 (10 months, p <0.003). Of multiple
      clinical, echocardiographic, and Doppler features entered into a multifactorial
      model, a ventricular area ratio < or = 2 remained the only independent predictor
      of survival. Patients with AL amyloid heart disease represent a heterogeneous
      population with regard to both prognosis and the relative degree of right to left
      ventricular dilation. RV dilation in patients with amyloid heart disease appears
      to be associated with more severe involvement and is associated with a very poor
      prognosis with a median survival of only 4 months.

PMID- 9285664
TI  - A genetic etiology for interruption of the aortic arch type B.
AB  - Interrupted aortic arch (IAA) type B is a congenital heart defect believed to be
      caused by an anomaly of bronchial arch mesenchymal development. IAA type B has
      been associated with DiGeorge syndrome (DGS), which includes conotruncal heart
      defects, T-cell immunodeficiency, hypocalcemia, and facial abnormalities. The
      great majority of DGS cases are associated with hemizygous deletions at the
      chromosome 22q11 locus. The present study was designed to establish the
      involvement of the 22q11 locus in the etiology of IAA type B, independently from
      the typical DGS phenotype. An evaluation was performed on 73 patients with
      conotruncal heart defects using fluorescence in situ hybridization (FISH)
      analysis with probes from the 22q11 DGS locus. From this group, 7 patients were
      deleted (including 4 of the 11 patients with IAA type B). FISH analysis was
      extended to a total of 22 patients with IAA type B and 11 of these (50%) were
      deleted. FISH and Southern blot analyses using additional markers within the
      DiGeorge chromosomal region were performed on patients found not to be deleted in
      the initial FISH screening. No small deletions or rearrangements were detected.
      In our patient population, a single, specific genetic defect is the basis for one
      half of the IAA type B cases. These data suggest that IAA type B is one of the
      most etiologically homogeneous congenital heart defects. A 22q11 deletion in IAA
      type B may or may not be associated with the typical DGS phenotype. Therefore,
      IAA type B, per se, should be an indication for 22q11 deletion testing.

PMID- 9285666
TI  - The time course of left ventricular remodeling after acute myocardial infarction.

PMID- 9285665
TI  - Midventricular diastolic pulse Doppler flow velocity profiles in the normal and
      abnormal left ventricle.
AB  - Diastolic function of the left ventricle (LV) is principally assessed by analysis
      of the Doppler velocity flow profiles at the mitral orifice (MO). Assuming the
      mitral valve is not obstructed, early and late diastolic inflow are influenced
      not only by the left atrium but also by the LV. We hypothesized that recording of
      diastolic flow velocity profiles in the mid LV might contribute additional
      information on the response of the ventricle to filling in diastole. In 58 normal
      subjects, the differences at the MO and midventricular (MV) levels between the R
      E interval (the time in milliseconds from the peak of the R wave of the
      electrocardiogram to the peak of the early diastolic filling wave), the R-D
      interval (the time in milliseconds from the peak of the R wave to the beginning
      of the early diastolic flow wave), and the D-E interval (the time in milliseconds
      from the onset to the peak of the early diastolic flow wave) were quite small,
      averaging 13 +/- 17, -21 +/- 27, and -7 +/- 16 ms, respectively (mean +/- SD). At
      the MO, the E/A velocity ratio averaged 1.6/1, whereas it was significantly
      greater at the MV level 2.1/1 (p <0.001) due to a relatively greater decrease in
      the A-wave velocity (37%) compared with the decrease in peak E-wave velocity
      (18%). The peak A-wave velocity occurred before the R wave (average 44 +/- 19 ms
      at the MO and 43 +/- 24 ms at the MV level). Abnormal patterns involving both
      early and late diastole were observed with left ventricular hypertrophy and
      systolic dysfunction. The method is simple and therefore adaptable for routine
      clinical practice. Importantly, early diastolic left ventricular function can be
      assessed in patients in atrial fibrillation as well as sinus rhythm.

PMID- 9285667
TI  - Value of leads V7-V9 in diagnosing posterior wall acute myocardial infarction and
      other causes of tall R waves in V1-V2.
AB  - Left posterolateral chest leads (V7, V8, V9) helped distinguish the multiple
      causes of tall R waves in V1 and/or V2, diagnosed true posterior myocardial
      infarction when standard leads did not, and identified the presence or absence of
      posterior injury in patients with inferior infarction.

PMID- 9285669
TI  - Electrocardiographic differentiation of the ST-segment depression of acute
      myocardial injury due to the left circumflex artery occlusion from that of
      myocardial ischemia of nonocclusive etiologies.
AB  - Lead distributions of peak ST-segment depression were compared between patients
      undergoing left circumflex artery percutaneous transluminal coronary angioplasty
      and exercise tolerance test. Localization of peak ST-segment depression to leads
      V2 or V3 was 96% specific and 70% sensitive for differentiating ischemia due to
      occlusion of left circumflex artery occlusion from nonocclusive ischemia.

PMID- 9285668
TI  - Usefulness of positive troponin-T and negative creatine kinase levels in
      identifying high-risk patients with unstable angina pectoris.
AB  - Troponin-T was measured in patients with chest pain and negative creatine
      phosphokinase-MB isoenzymes. Patients with elevated troponin-T had a
      significantly greater risk of cardiac events over the next 6 months than patients
      with normal troponin-T.

PMID- 9285670
TI  - Directed proximal magnetic resonance coronary angiography compared with
      conventional contrast coronary angiography.
AB  - Magnetic resonance coronary angiography in 36 patients with proximal 1-vessel
      disease within 1 week of contrast coronary angiography was performed and the time
      required to complete the study was 13.4 +/- 4.2 min 13.2 +/- 8.1 minutes for the
      right and left coronary arteries, respectively. The sensitivity, specificity,
      positive and negative predictive values, and accuracy of magnetic resonance
      coronary angiography were 100% for right cronary artery disease, and 83%, 98%,
      94%, 94%, and 94%, respectively, for left coronary artery disease.

PMID- 9285671
TI  - Quinidine versus propafenone for conversion of atrial fibrillation to sinus
      rhythm.
AB  - The efficacy and safety of quinidine, as a rapid oral loading therapy, and
      propafenone in the conversion of atrial fibrillation of <6 months duration to
      sinus rhythm were compared. Quinidine was more efficacious and as well tolerated
      as propafenone.

PMID- 9285672
TI  - Association between diuretic use, clinical response, and death in acute heart
      failure.
AB  - Because the impact of diuretic use on mortality in acute congestive heart failure
      (CHF) is not known, we examined the association between drug use, fluid balance,
      and death among 1,150 patients hospitalized for evaluation and treatment of CHF.
      After adjusting for other relevant intergroup differences, we observed that less
      net weight loss and a greater number of intravenous drug doses retained
      significant predictive value for death, suggesting that more frequent diuretic
      dosing or diuretic resistance may be related to mortality in acute CHF.

PMID- 9285673
TI  - Usefulness of dobutamine echocardiography in the hemodynamic assessment of
      mechanical prostheses in the aortic valve position.
AB  - Dobutamine stress echocardiography is a simple, safe, and readily available
      method to evaluate prosthetic valve hemodynamics under various flow conditions. A
      normal response of aortic valve prostheses to dobutamine infusion is a 100%
      increment in transprosthetic pressure gradients with an unchanged valve area.

PMID- 9285674
TI  - Comparison of frequency of left atrial thrombus in patients with mechanical
      prosthetic cardiac valves and stroke versus transient ischemic attacks.
AB  - Transesophageal echocardiography performed in a group of 36 patients who had a
      first cerebral embolic event after implantation of a mechanical cardiac valvular
      prosthesis revealed that stroke is associated with the presence of left atrial
      thrombi more frequently than transient ischemic attacks. Intracardiac embolic
      sources other than thrombi are possibly related more often to the latter type of
      cerebral embolism in this patient population.

PMID- 9285676
TI  - Cardiac transplantation in adults with small hearts.
AB  - Cardiac transplantation is performed in some adults having cardiac conditions
      causing considerable cardiac dysfunction in the absence of an increase in cardiac
      mass.

PMID- 9285675
TI  - Work time required to perform diagnostic and interventional pediatric cardiac
      catheterizations.
AB  - This study was designed to determine the time required to perform pediatric
      diagnostic and interventional heart catheterizations. These data are the first
      published information evaluating such work times.

PMID- 9285677
TI  - Acute hemodynamic effects of estrogen administration in postmenopausal women.
AB  - The hemodynamic effects of estrogens in replacement doses have not been fully
      clarified; therefore, we studied the acute hemodynamic changes after 0.625 and
      1.25 mg of conjugated estrogens, administered intravenously, using a
      thermodilution catheter, in postmenopausal women without structural heart
      disease. Pulmonary and systemic pressures and resistances and stroke volume did
      not change compared with baseline, but heart rate and cardiac output decreased
      significantly, which may be associated with estrogen's previously described
      calcium-blocking effect or with a more recently contemplated beta-blocking
      action.

PMID- 9285678
TI  - Intracardiac versus transthoracic echocardiographic imaging of translation and
      rotation of left ventricular center of cavity area in dogs.
AB  - Motion of the left ventricular cavity center during the cardiac cycle was
      compared using transthoracic and intracardiac echocardiography. Rotation was
      comparable for the 2 methods, however, translation of the left ventricular cavity
      area center was greater with intracardiac echocardiography.

PMID- 9285679
TI  - Dissection of the ascending aorta induced by coronary angiography.
AB  - We present a 75-year-old woman with an iatrogenic dissection of the ascendin
      aorta, induced by stenting of the right coronary artery. Coronary angiographic
      and transesophageal echocardiographic imaging and histology are presented.

PMID- 9285680
TI  - Transmyocardial laser revascularization using a thoracoscopic approach.
AB  - Transmyocardial revascularization is a new technique aimed to improve perfusion
      of the ischemic myocardium by creating transmyocardial channels with a laser.
      This report demonstrates that transmyocardial revascularization with a holmium
      laser can be performed through a thoracoscopic approach.

PMID- 9285681
TI  - Longitude, the Longitude Act, scurvy, and the beginning of government-supported
      research.

PMID- 9285682
TI  - Risk for exercise-induced myocardial injury for athletes performing prolonged
      strenuous endurance exercise.

PMID- 9285683
TI  - Association of PTP-PEST with the SH3 domain of p130cas; a novel mechanism of
      protein tyrosine phosphatase substrate recognition.
AB  - The protein tyrosine phosphatase PTP-PEST displays remarkable substrate
      specificity, in vitro and in vivo for p130cas a signalling intermediate
      implicated in mitogenic signalling, cell-adhesion induced signalling, and in
      transformation by a variety of oncogenes. We have identified a high affinity
      interaction between the SH3 domain of p130cas and a proline-rich sequence
      (P335PPKPPR) within the C-terminal segment of PTP-PEST. Mutation of proline 337
      within this sequence to alanine significantly impairs the ability of PTP-PEST to
      recognise tyrosine phosphorylated p130cas as a substrate, without qualitatively
      affecting the selectivity of the interaction. Thus the highly specific nature of
      the interaction between PTP-PEST and p130cas appears to result from a combination
      of two distinct substrate recognition mechanisms; the catalytic domain of PTP
      PEST contributes specificity to the interaction with p130cas, whereas the SH3
      domain-mediated association of p130cas and PTP-PEST dramatically increases the
      efficiency of the interaction. Furthermore, our results indicate that one
      important function of the p130cas SH3 domain is to associate with PTP-PEST and
      thereby facilitate the dephosphorylation of p130cas, resulting in the termination
      of tyrosine phosphorylation-dependent signalling events downstream of p130cas.

PMID- 9285684
TI  - The polyproline region of p53 is required to activate apoptosis but not growth
      arrest.
AB  - p53 is a pivotal regulator of apoptosis but its mechanism of action is obscure.
      We report that the polyproline (PP) region located between p53's transactivation
      and DNA binding domains is necessary to induce apoptosis but not cell growth
      arrest. The PP region was dispensable for DNA binding, inhibition of SAOS-2 tumor
      cell growth, suppression of E1A + RAS cell transformation, and cell cycle
      inhibition. A temperature-sensitive dominant inhibitory p53 mutant lacking PP
      (p53ts deltaPP) retained its ability to cooperate with adenovirus E1A in
      transformation of primary BRK cells. However, while activation of wt p53 induced
      apoptosis in E1A + p53ts-transformed cells, activation of p53 deltaPP induced
      cell cycle arrest but not apoptosis in E1A + p53ts deltaPP-transformed cells.
      Similarly, PP deletion abolished apoptosis in LoVo colon carcinoma cells, which
      are killed by wt p53 overexpression. Transactivation was largely unaffected by PP
      deletion. Significantly, BAX induction was intact, indicating that additional
      events are required for p53 to induce apoptosis. As a recently described site for
      familial mutation in at least one breast cancer family, the PP region represents
      a domain that may be altered in human tumors. We concluded that p53's ability to
      induce apoptosis is dispensable for inhibiting cell growth and transformation and
      that the PP region plays a crucial role in apoptotic signaling.

PMID- 9285685
TI  - Pertubation of B and T cell development and predisposition to lymphomagenesis in
      Emu Bmi1 transgenic mice require the Bmi1 RING finger.
AB  - Proviral activation of the Bmi1 gene has implicated Bmi1 as a collaborator of c
      Myc in lymphomagenesis. To determine the effect of Bmi1 overexpression on
      hematopoiesis and lymphomagenesis transgenic mice were generated that overexpress
      different forms of the Bmi1 protein in their lymphoid compartment. Emu Bmi1
      transgenic mice, overexpressing the wild type Bmi1 protein showed a perturbed
      lymphoid development and were highly susceptible to B and T cell lymphomagenesis.
      Mutational analysis of the Bmi1 protein demonstrated that the conserved N
      terminal RING finger and central part of Bmi1 are essential for its oncogenic
      potential whereas the C-terminal Pro-Ser rich region is not required. We have
      used provirus tagging in the Emu Bmi1 mice to identify genes that cooperate with
      Bmi1 in lymphomagenesis. MoMLV infection in Emu Bmi1 transgenic mice accelerated
      lymphoma development. Proviral activation of the Pim and Myc genes but not the
      Gfi1 gene were frequently observed in these tumors. These results demonstrate
      that Bmi1 is a potent oncogene and suggest that it plays an important role in
      early lymphoid development.

PMID- 9285686
TI  - Protein phosphatase 2A subunit assembly: the catalytic subunit carboxy terminus
      is important for binding cellular B subunit but not polyomavirus middle tumor
      antigen.
AB  - The carboxy terminus of protein phosphatase 2A (PP2A) catalytic subunit is highly
      conserved. Seven out of the last nine residues, including two potential in vivo
      phosphorylation sites, threonine 304 and tyrosine 307, are completely invariant
      in all known PP2As. Mutational analysis of the carboxy terminus in vivo was
      facilitated by efficient immunoprecipitation of trimeric PP2A holoenzyme via an
      epitope-tagged catalytic subunit. The results indicate that the catalytic subunit
      carboxy terminus is important for complex formation with the PP2A 55 kDa
      regulatory B subunit, but not with polyomavirus oncogene, middle tumor antigen
      (MT), a viral B-type regulatory subunit. Replacing catalytic subunit threonine
      304 or tyrosine 307 with a negatively charged amino acid abolished binding of the
      B subunit to the dimeric enzyme core and altered substrate specificity. Certain
      other amino acid substitutions of different size and/or charge also abolished or
      greatly reduced B subunit binding. Substitution of alanine at position 304 or
      phenylalanine at position 307 did not dramatically reduce B subunit binding or
      phosphatase activity in vitro, yet the latter substitutions are not found in
      naturally occurring PP2As. Thus, the wild-type residues are important for a yet
      unknown function in vivo. Additionally, deleting the carboxy terminal nine amino
      acids inhibited binding of the B subunit to the dimeric enzyme core, indicating a
      requirement for one or more of these amino acids for complex formation. MT
      interaction with the dimeric PP2A enzyme core was not inhibited by any of these
      mutations. Finally, unlike B subunit, MT does not activate the phosphatase
      activity of the PP2A heterodimer towards cdc2-phosphorylated histone H1.

PMID- 9285687
TI  - The murine Tcl1 oncogene: embryonic and lymphoid cell expression.
AB  - In human leukemias and lymphomas nonrandom chromosomal rearrangements cause
      changes in cell growth and/or survival in such a way as to promote malignancy.
      The detailed study of the biochemical and genetic pathways altered in human
      cancer requires the identification or development of models to allow the study
      and manipulation of cancer gene function. Recently, the breakpoint gene TCL1,
      involved in chromosome translocations observed mostly in mature T-cell
      proliferations and chronic lymphocytic leukemias (CLL), was isolated and
      characterized, and showed to be part of a new gene family of proteins involved in
      these tumors. The murine Tcl1 gene, is similar in sequence to the murine and
      human MTCP1 gene also involved in T cell leukemias. The murine Tcl1 gene was
      shown to reside on mouse chromosome 12 in a region syntenic to human chromosome
      14. Furthermore, we show that the murine Tcl1 gene is expressed early in mouse
      embryonic development and demonstrates expression in fetal hematopoietic organs
      as well as in immature T and B cells. Characterization of the murine Tcl1 gene
      will help in developing a mouse model of CLL and would provide the best
      opportunity to study and decipher the role of TCL1 in malignant transformation.

PMID- 9285689
TI  - Differential expression patterns of the PEA3 group transcription factors through
      murine embryonic development.
AB  - ERM, ER81 and PEA3 are three highly related transcription factors belonging to
      the ETS family. Together they form the PEA3 group within this family. Little data
      is yet available regarding the roles of these three genes during embryonic
      development. A prerequisite to investigations in this field is to obtain an
      accurate spatio-temporal expression map for the erm, er81 and pea3 genes. To this
      end, we have used in situ hybridization to compare their expression patterns
      during critical stages of murine embryogenesis. We report that all three genes
      are expressed in numerous developing organs coming from different embryonic
      tissues. The three genes appeared co-expressed in different organs but presented
      specific sites of expression, so that the resultant expression pattern could in
      fact reveal several distinct functions depending upon isolated and/or various
      combinations of the PEA3 member expression. These results suggest that erm, er81
      and pea3 genes are differentially regulated, probably to serve important
      functions as cell proliferation control, tissue interaction mediator or cell
      differentiation, all over successive steps of the mouse organogenesis.

PMID- 9285688
TI  - Expression of teratocarcinoma-derived growth factor-1 (TDGF-1) in testis germ
      cell tumors and its effects on growth and differentiation of embryonal carcinoma
      cell line NTERA2/D1.
AB  - The teratocarcinoma-derived growth factor-1 (TDGF-1) gene codes for a 188
      aminoacid glycoprotein that shares structural homology with the epidermal growth
      factor (EGF) family of growth factors. TDGF-1 is highly expressed in the
      undifferentiated embryonal carcinoma stem cell line NTERA2 clone D1 (NT2/D1) and
      its expression is downregulated in response to differentiating agents such as
      retinoic acid (RA) and hexamethylen-bisacetamide (HMBA). To assess the role of
      TDGF-1 in the onset and/or progression of human germ cell tumors, we analysed
      TDGF-1 expression by Northern blot and immunostaining in a panel of 59 human germ
      cell tumors of different histological origins. We show that TDGF-1 expression is
      markedly elevated in a subset of human testicular germ cell tumors as compared to
      normal testes. TDGF-1 overexpression occurs in about 100% of tumors with non
      seminomatous phenotype, such as embryonal carcinomas and malignant
      undifferentiated teratocarcinomas. To address the questions of how TDGF-1
      (previously called CRIPTO) may affect the growth and/or the differentiation of
      embryonal carcinoma cells, we have characterized the effects of exogenous
      recombinant TDGF-1 protein on the proliferation rate and differentiation
      'potential of NT2/D1. Exogenous TDGF-1 protein stimulated DNA synthesis and cell
      proliferation in both undifferentiated and differentiated NT2/D1 cells. However,
      TDGF-1 protein treatment was unable to block differentiation induced by both RA
      and HMBA. These results suggest that TDGF-1 growth factor may represent an
      autocrine growth factor that may be involved in the process of development of
      testicular neoplasms.

PMID- 9285690
TI  - Chemosensitization of HER-2/neu-overexpressing human breast cancer cells to
      paclitaxel (Taxol) by adenovirus type 5 E1A.
AB  - Breast cancer cells that overexpress HER-2/neu are more resistant to
      chemotherapeutic agents such as paclitaxel (Taxol) and docetaxel (Taxotere) than
      those that do not overexpress HER-2/neu. In previous work, we showed that the
      adenovirus type 5 E1A can repress HER-2/neu expression at the transcriptional
      level. Here we first demonstrated that paclitaxel sensitivity correlates with HER
      2/neu expression level in a panel of mouse fibroblasts expressing different
      levels of HER-2/ neu, and that downregulation of HER-2/neu expression by E1A
      sensitizes the cells to paclitaxel. To further test whether E1A can sensitize HER
      2/neu-overexpressing human breast cancer cells to paclitaxel through E1A-mediated
      HER-2/neu repression, an adenoviral vector was used to transfer the E1A gene into
      two human breast cancer cell lines, MDA-MB-453 and MDA-MB-361, that overexpress
      HER-2/neu. After E1A delivery, we observed that HER-2/neu expression level was
      reduced, and cells were treated with paclitaxel. Cell proliferation assays showed
      a synergistic growth inhibition effect of E1A and paclitaxel. The synergistic
      effect was also confirmed by soft agar colony-formation assay. Breast cancer cell
      lines that express low levels of HER-2/neu, MDA-MB-435 and MDA-MB-231 cells
      showed no synergistic growth inhibition effect when treated on the same
      protocols. Thus, we concluded that the adenovirus type 5 E1A gene can sensitize
      paclitaxel-resistant HER-2/neu-overexpressing breast cancer cells to the drug by
      repressing HER-2/neu expression. This in turn may have important implications for
      the development of a novel therapy that combines chemotherapy and gene therapy.

PMID- 9285691
TI  - Co-operation of simian virus 40 T antigen and insulin receptor substrate-1 in
      protection from apoptosis induced by interleukin-3 withdrawal.
AB  - 32D cells are interleukin-3 (IL-3) dependent murine hemopoietic cells, that
      undergo apoptosis after IL-3 withdrawal. An overexpressed insulin-like growth
      factor I receptor (IGF-IR) protects these cells from apoptosis induced by IL-3
      withdrawal. When 32D cells are stably transfected with plasmids expressing either
      IRS-1 (a major substrate of the IGF-IR) or the Simian virus 40 large T antigen,
      singly, they still undergo apoptosis after IL-3 withdrawal, although IRS-1 offers
      partial protection. The cells, however, are fully protected when they are stably
      transfected with both IRS-1 and SV40 T antigen. Protection from apoptosis in
      these cells is characterized by the stabilization of the Stat1 and Stat5 protein
      levels, whose synthesis is inhibited when IL-3 is withdrawn.

PMID- 9285692
TI  - v-Rel prevents apoptosis in transformed lymphoid cells and blocks TNFalpha
      induced cell death.
AB  - The v-Rel oncoprotein belongs to the Rel/NF-kappaB family of transcription
      factors. It transforms chicken lymphoid cells in vitro and induces fatal
      lymphomas in vivo. In this study, we used a tetracycline-regulated system to
      characterize the role of v-Rel in cell transformation. We show that the continued
      expression of v-Rel is necessary to maintain the viability of transformed
      lymphoid cells and enables primary spleen cells to escape apoptosis in vitro
      culture. In agreement with a possible role for v-Rel in the inhibition of
      programmed cell death, its inducible expression in HeLa cells prevented TNFalpha
      induced apoptosis. While the repression of v-Rel was accompanied by the rapid
      degradation of IkappaBalpha, changes in the steady-state levels of the apoptosis
      inhibitors Bcl-2 and Bcl-X(L) were only observed following the onset of cell
      death in transformed lymphoid cells. This suggests that the anti-apoptotic
      activity of v-Rel may affect other apoptosis inhibitors or other factors in the
      death pathway. Together, these findings demonstrate that v-Rel blocks apoptosis
      and suggest that this activity may be an important component of its transforming
      function.

PMID- 9285693
TI  - Coactivation of AP-1 activity and TGF-beta1 gene expression in the stress
      response of normal skin cells to ionizing radiation.
AB  - Activation of the AP-1 transcription factor and TGF-beta1 growth factor by
      ionizing radiation was studied both in vivo in pig skin, and in vitro in human
      fibroblasts and keratinocytes. Three and 6 h after irradiation, the Fos and Jun
      proteins and their binding activity to an AP-1 consensus sequence were strongly
      induced by high doses of gamma-rays. c-Fos, c-Jun and JunB proteins were found to
      be present in gel-shift complexes by probing with specific antibodies. Both
      keratinocytes and fibroblasts exhibited heightened AP-1 activity following
      irradiation. As we previously found that TGF-beta1 is involved in the development
      of skin lesions induced by radiation, TGF-beta1 gene expression was also
      examined. Two and 6 h after irradiation, the levels of TGF-beta1 transcripts were
      increased in skin. By immunostaining, TGF-beta1 protein levels were found to be
      increased in fibroblasts, keratinocytes and endothelial cells. As the TGF-beta1
      promoter contains AP-1 binding sites, the relation between AP-1 activity and TGF
      beta1 induction was addressed. The -365 TGF-beta1 promoter fragment, which
      contains a high affinity AP-1 site, exhibited increased binding to Jun and Fos
      proteins following irradiation. These results suggest that stress-inducible TGF
      beta1 expression is mediated by the activation of AP-1 transcription factor.

PMID- 9285696
TI  - Cell polarity: par for the polar course.
AB  - The nematode PAR-1 gene is required for asymmetric cell divisions during
      development. Recently identified mammalian Par-1 homologues are kinases that
      phosphorylate microtubule-associated proteins; their overexpression disrupts the
      microtubule cytoskeleton, and alters cellular structure and organization.

PMID- 9285695
TI  - New deletion in low-grade oligodendroglioma at the glioblastoma suppressor locus
      on chromosome 10q25-26.
AB  - Loss of heterozygosity on chromosome 10 is considered to be associated with the
      progression of glioblastomas. Two closely related regions have recently been
      proposed to contain the glioblastoma suppressor locus on chromosome 10q25-26; a 1
      cM region between the polymorphic (CA)n-repeat markers D10S587 and D10S216, and
      an area of 5 cM between the markers D10S221 and D10S209. To confirm and further
      delineate this region, we analyzed 51 glioblastomas and 11 intermediate and low
      grade gliomas for loss of heterozygosity on chromosome 10. 47/62 mostly malignant
      gliomas displayed complete loss of chromosome 10 and nine tumors were unaltered,
      whereas four glioblastomas and two low-grade oligodendrogliomas had partial loss
      on distal 10q. With these six tumors, we constructed a deletion map with
      increased marker density at 10q25-26 which shows two centromeric breakpoints at
      the markers D10S587 and D10S216, thus only confirming the distal, but not the
      proximal candidate glioblastoma suppressor locus. Two out of four low-grade
      oligodendrogliomas displayed partial deletions on 10q25-26. This suggests that
      deletion on chromosome 10 is not merely a late event in the progression of
      glioblastomas, but could play a role earlier in the development of gliomas.

PMID- 9285697
TI  - Genetic probes: new ways to watch cells in action.
AB  - Visualizing fast physiological changes in small living cells, such as synaptic
      transmission in a neural circuit, is a fundamental problem in biology. Progress
      towards this goal is being made with the development of new types of protein
      sensor that can be targeted within cells and organisms.

PMID- 9285694
TI  - Regulation of tumor suppressor proteins, p53 and retinoblastoma, by estrogen and
      antiestrogens in breast cancer cells.
AB  - We have utilized the estrogen receptor (ER)-positive human breast carcinoma cell
      line, T47D, to determine the role of ER in regulating cell proliferation, the
      level of expression of p53 and the state of phosphorylation of retinoblastoma
      protein (pRB) by 17 beta-estradiol (E2) and antiestrogens. T47D cells cultured
      for 7 days proliferated rapidly expressing maximal levels of p53 in medium
      containing 5% fetal bovine (whole) serum. Exogenously added E2 had no effect on
      either of the above parameters. The antiestrogen, ICI 164,384 (ICI, 1 microM),
      decreased cell number and p53 level to nearly 20% of the control. Comparatively,
      a treatment of the cells with 100 nM 4OH-tamoxifen (OHT) decreased cell number to
      40% of the control without a concomitant decrease in the p53 levels suggesting a
      differential ability of these antiestrogens to regulate p53 levels in cells
      cultured in whole serum. When cells were cultured in medium containing serum
      depleted of endogenous steroids (charcoal stripped serum), cell number and p53
      levels declined. Treatment with exogenous E2 (1 nM) increased cell proliferation,
      p53 expression and phosphorylation of pRB. The antiestrogens ICI and OHT blocked
      these E2 effects, demonstrating a direct antagonism of ER by ICI and OHT. These
      results indicate an ER-mediated mechanism for coordinate expression of p53 and
      hyperphosphorylation of pRB during E2-induced proliferation of T47D cells.

PMID- 9285698
TI  - Enveloped viruses: a common mode of membrane fusion?.
AB  - Viruses use elaborate stratagems to enter cells. The HIV-1 envelope glycoprotein,
      which mediates both attachment and membrane fusion, has grudgingly begun to yield
      high-resolution structural information that suggests mechanistic similarities
      with the hemagglutinin protein of influenza virus.

PMID- 9285699
TI  - Oocyte differentiation: a motor makes a difference.
AB  - In a variety of developmental systems, asymmetric mitoses precede, and are
      essential for, cellular differentiation. Recent studies demonstrate a role for
      the motor protein cytoplasmic dynein in generating the mitotic asymmetries that
      lead to Drosophila oocyte differentiation.

PMID- 9285701
TI  - Bacterial pathogenesis: a variation on variation in Lyme disease.
AB  - The discovery of antigenic variation in Borrelia burgdorferi, the bacterium that
      causes Lyme disease, provides a potential explanation for the chronic nature of
      infection as well as new insights into the genetic structure of highly
      recombinogenic loci responsible for combinatorial genetic diversification.

PMID- 9285700
TI  - DNA repair: caretakers of the genome?.
AB  - Recent results show that the 8-oxoguanine DNA repair system is functionally
      conserved in bacteria and mammals. The bacterial system protects the genome from
      the mutagenic effects of oxidative stress; the role of the mammalian system is
      expected to be similar and defects in it may increase susceptibility to cancer.

PMID- 9285702
TI  - Photosynthesis: a new twist to biological solar power.
AB  - New crystallographic data for the bacterial photoreaction centre have brought an
      intriguing insight into the structural changes that accompany the primary event
      in photosynthesis, the conversion of light energy into chemical energy.

PMID- 9285703
TI  - Drosophila morphogenesis: movements behind the edge.
AB  - Coordinated cell movements during development require extensive exchange of
      information between the cells involved. Recent results suggest a connection
      between two signalling pathways during dorsal closure in the Drosophila embryo.

PMID- 9285704
TI  - Cell death: fatal induction in plants.
AB  - The recent molecular characterization of three plant genes in which mutations
      cause phenotypes that mimic disease responses has provided interesting new
      insights into cell death in plants, but many questions remain about the nature
      and physiological importance of the process.

PMID- 9285705
TI  - Calcium signalling: how do IP3 receptors work?
AB  - The intracellular receptor for inositol 1,4,5-trisphosphate (IP3) is responsible
      for generation and control of very complex Ca2+ signals. New experimental
      approaches to studying the kinetics of the IP3 receptor are now beginning to give
      some insight into the mechanisms behind its rather bizarre properties.

PMID- 9285706
TI  - Molecular chaperones: avoiding the crowd.
AB  - The involvement of two types of molecular chaperone in folding newly synthesized
      proteins can be rationalized in terms of the crowded nature of the intracellular
      environment. Recent work sheds light on how these chaperones recognise their
      substrates and protect them from the problems of macromolecular crowding.

PMID- 9285707
TI  - Protein degradation: the ins and outs of the matter.
AB  - In eukaryotic cells, nascent membrane or secretory proteins are translocated into
      the endoplasmic reticulum through the Sec61p translocation channel; recent
      evidence suggests that, if they fail to achieve a native conformation, they are
      translocated back into the cytosol by the same route and degraded by the
      proteasome.

PMID- 9285708
TI  - Bacterial cytokinesis: let the light shine in.
AB  - Recent application of fluorescence microscopy to the study of the bacterial cell
      cycle has revealed the existence of a cytoskeletal element - once thought to
      occur only in eukaryotic cells - that mediates cytokinesis, and possibly another
      involved in chromosome segregation.

PMID- 9285709
TI  - Vertebrate evolution: something fishy about Hox genes.
AB  - The complete Hox gene complement of the Japanese pufferfish has now been
      determined, together with the genomic organisation of all four Hox gene clusters.
      One of the many surprises is that this strange fish has lost an unusually large
      number of Hox genes.

PMID- 9285710
TI  - Memory and behavior: a second generation of genetically modified mice.
AB  - The use of standard genetic techniques, such as gene targeting and transgenesis,
      to study cognitive function in adult animals suffers from the limitations that
      the gene under study is often altered in many brain regions, and that this
      alteration is present during the entire developmental history of the animal.
      Furthermore, to relate cognitive defects to neuronal mechanisms of memory,
      studies have relied on examining long-term potentiation - an artificially induced
      form of synaptic plasticity. Recent technical advances allow the expression of a
      genetic alteration in mice to be restricted both anatomically and temporally,
      making possible a more precise examination of the role of various forms of
      synaptic plasticity, such as long-term potentiation and long-term depression, in
      memory formation. Recordings from so-called 'place cells' -hippocampal cells that
      encode spatial location -in freely moving, genetically modified mice have further
      advanced our understanding of how the actual cellular representation of space is
      influenced by genetic alterations that affect long-term potentiation.

PMID- 9285711
TI  - The small GTPases Cdc42Hs, Rac1 and RhoG delineate Raf-independent pathways that
      cooperate to transform NIH3T3 cells.
AB  - BACKGROUND: Ras-mediated transformation of mammalian cells has been shown to
      activate multiple signalling pathways, including those involving mitogen
      activated protein kinases and the small GTPase Rho. Members of the Rho family
      affect cell morphology by controlling the formation of actin-dependent
      structures: specifically, filopodia are induced by Cdc42Hs, lamellipodia and
      ruffles by Rac, and stress fibers by RhoA. In addition, Rho GTPases are involved
      in progression through the G1 phase of the cell cycle, and Rac1 and RhoA have
      recently been directly implicated in the morphogenic and mitogenic responses to
      transformation by oncogenic Ras. In order to examine the cross-talk between Ras
      and Rho proteins, we investigated the effects on focus-forming activity and cell
      growth of the Rho-family members Cdc42Hs, Rac1 and RhoG by expressing
      constitutively active or dominant-negative forms in NIH3T3 cells. RESULTS:
      Expression of Rac1 or RhoG modulated the saturation density to which the cells
      grew, probably by affecting the level of contact inhibition. Although all three
      GTPases were required for cell transformation mediated by Ras but not by
      constitutively active Raf, the selective activation of each GTPase was not
      sufficient to induce the formation of foci. The coordinated activation of
      Cdc42Hs, RhoG and Rac1, however, elicited a high focus-forming activity,
      independent of the mitogen-activated ERK and JNK protein kinase pathways.
      CONCLUSIONS: Ras-mediated transformation induces extensive changes in cell
      morphology which require the activity of members of the Rho family of GTPases.
      Our data show that the pattern of coordinated Rho family activation that elicits
      a focus-forming activity in NIH3T3 cells is distinct from the regulatory cascade
      that has been proposed for the control of actin-dependent structures in Swiss 3T3
      cells.

PMID- 9285712
TI  - The protein tyrosine phosphatase SHP-2 negatively regulates ciliary neurotrophic
      factor induction of gene expression.
AB  - Ciliary neurotrophic factor, along with other neuropoietic cytokines, signals
      through the shared receptor subunit gp130 [1-3], leading to the tyrosine
      phosphorylation of a number of substrates [4,5], including the transcription
      factors STAT1 and STAT3 and the protein tyrosine phosphatase SHP-2 [6,7] [8]. SHP
      2 (also known as PTP1D, SHPTP2, Syp and PTP2C) is a positive regulatory molecule
      required for the activation of the mitogen-activated protein kinase pathway and
      the stimulation of gene expression in response to epidermal growth factor,
      insulin and platelet-derived growth factor stimulation [9-11]. We have previously
      shown that cytokines that signal via the gp130 receptor subunit activate
      transcription of the vasoactive intestinal peptide (VIP) gene through a 180 bp
      cytokine response element (CyRE) [12,13]. To characterize the role of SHP-2 in
      the regulation of gp130-stimulated gene expression, we examined the regulation of
      the VIP CyRE in two systems that prevented ligand-dependent SHP-2
      phosphorylation. Inhibition of SHP-2, either by mutating the tyrosine residue in
      gp130 that mediates the SHP-2 interaction, or by expression of dominant-negative
      SHP-2, resulted in dramatic increases in gp130-dependent gene expression, through
      the VIP CyRE and more specifically through multimerized STAT-binding sites. These
      data suggest that SHP-2 has a negative role in gp130 signaling by modulating STAT
      mediated transcriptional activation.

PMID- 9285714
TI  - Imaging green fluorescent protein fusion proteins in Saccharomyces cerevisiae.
AB  - Tagging expressed proteins with the green fluorescent protein (GFP) from Aequorea
      victoria [1] is a highly specific and sensitive technique for studying the
      intracellular dynamics of proteins and organelles. We have developed, as a probe,
      a fusion protein of the carboxyl terminus of dynein and GFP (dynein-GFP), which
      fluorescently labels the astral microtubules of the budding yeast Saccharomyces
      cerevisiae. This paper describes the modifications to our multimode microscope
      imaging system [2,3], the acquisition of three-dimensional (3-D) data sets and
      the computer processing methods we have developed to obtain time-lapse recordings
      of fluorescent astral microtubule dynamics and nuclear movements over the
      complete duration of the 90-120 minute yeast cell cycle. This required low
      excitation light intensity to prevent GFP photobleaching and phototoxicity,
      efficient light collection by the microscope optics, a cooled charge-coupled
      device (CCD) camera with high quantum efficiency, and image reconstruction from
      serial optical sections through the 6 micron-wide yeast cell to see most or all
      of the astral molecules. Methods are also described for combining fluorescent
      images of the microtubules labeled with dynein-GFP with high resolution
      differential interference contrast (DIC) images of nuclear and cellular
      morphology [4], and fluorescent images of the chromosomes stained with 4,6
      diamidino-2-phenylindole (DAPI) [5].

PMID- 9285713
TI  - Acetylation of general transcription factors by histone acetyltransferases.
AB  - The acetylation of histones increases the accessibility of nucleosomal DNA to
      transcription factors [1,2], relieving transcriptional repression [3] and
      correlating with the potential for transcriptional activity in vivo [4 - 7]. The
      characterization of several novel histone acetyltransferases - including the
      human GCN5 homolog PCAF (p300/CBP-associated factor) [8], the transcription
      coactivator p300/CBP [9], and TAFII250 [10] - has provided a potential
      explanation for the relationship between histone acetylation and transcriptional
      activation. In addition to histones, however, other components of the basal
      transcription machinery might be acetylated by these enzymes and directly affect
      transcription. Here, we examine the acetylation of the basal transcriptional
      machinery for RNA polymerase II by PCAF, p300 and TAFII250. We find that all
      three acetyltransferases can direct the acetylation of TFIIEbetaand TFIIF, and we
      identify a preferred site of acetylation in TFIIEbeta. Human TFIIE consists of
      two subunits, alpha(p56) and beta(p34), which form a heterotetramer (alpha2
      beta2) in solution ([11], reviewed in [12]). TFIIE enters the preinitiation
      complex after RNA polymerase II and TFIIF, suggesting that TFIIE may interact
      directly with RNA polymerase II and/or TFIIF [13,14]. In addition, TFIIE can
      facilitate promoter melting either in the presence or absence of TFIIH and can
      stimulate TFIIH-dependent phosphorylation of the carboxy-terminal domain of RNA
      polymerase II [15-18]. TFIIF has an essential role in both transcription
      initiation and elongation ([19,20], for review see [21]). We discuss the
      implications of the acetylation of TFIIEbetaand TFIIF for transcriptional control
      by PCAF, p300 and TAFII250.

PMID- 9285715
TI  - The simian retrovirus-1 constitutive transport element, unlike the HIV-1 RRE,
      uses factors required for cellular mRNA export.
AB  - BACKGROUND: A hallmark of retroviral gene expression is that unspliced retroviral
      genomic RNA is exported to the cytoplasm, whereas endogenous intron-containing
      cellular RNAs are usually retained in the nucleus. In complex retroviruses, such
      as human immunodeficiency virus-1 (HIV-1), nuclear export is accomplished by the
      interaction of a virally encoded protein, Rev, with a cis-acting RNA element, the
      Rev-responsive element (RRE). In type D retroviruses, such as the simian
      retrovirus type 1 (SRV-1), however, genomic RNA is exported by cellular factor(s)
      that interact with a conserved cis-acting RNA element, the constitutive transport
      element (CTE). RESULTS: We found that the CTE was exported in a specific and
      saturable fashion from Xenopus oocyte nuclei. When inserted into the intron of an
      adenovirus-derived pre-mRNA, the CTE did not affect splicing efficiency but
      promoted the nuclear export of the excised intron lariat that is normally
      retained within the nucleus. Export of CTE-containing RNAs to the cytoplasm was
      not affected by the heterogeneous nuclear ribonucleoprotein A1 or an excess of
      peptides corresponding to the Rev nuclear export signal. Microinjection of
      saturating amounts of CTE RNA did not affect tRNA export or Rev-mediated export
      but did inhibit mRNA export. CTE-mediated export was found to be dependent on Ran
      mediated GTP hydrolysis. CONCLUSION: The Rev-RRE system and the CTE direct intron
      containing RNAs to distinct export pathways. Although previous data have
      suggested that Rev uses the same export pathway as uracil-rich small nuclear RNAs
      and 5S ribosomal RNA, the CTE seems to interact with evolutionarily conserved
      factors that are essential for cellular mRNA export.

PMID- 9285716
TI  - TYMSTR, a putative chemokine receptor selectively expressed in activated T cells,
      exhibits HIV-1 coreceptor function.
AB  - BACKGROUND: Chemokines bind to specific receptors and mediate leukocyte migration
      to sites of inflammation. Recently, some chemokine receptors, notably CXCR4 and
      CCR5, have been shown to be essential fusion factors on target cells for
      infection by human immunodeficiency virus (HIV); the chemokines bound by these
      receptors have also been shown to act as potent inhibitors of HIV infection.
      Here, we describe the isolation of a novel, putative chemokine receptor. RESULTS:
      We have isolated the cDNA for a putative human chemokine receptor, which we have
      termed TYMSTR (T-lymphocyte-expressed seven-transmembrane domain receptor). The
      TYMSTR gene is localized to human chromosome 3 and encodes a protein that has a
      high level of identity with chemokine receptors. TYMSTR mRNA was selectively
      expressed in interleukin-2-stimulated T lymphocytes but not in freshly isolated
      lymphocytes and leukocytes or related cell lines. The natural ligand for TYMSTR
      was not identified among 32 human chemokines and other potential ligands. Cells
      co-expressing TYMSTR and human CD4 fused with cells expressing envelope
      glycoproteins of macrophage (M)-tropic HIV-1 as well as T-cell line (T)-tropic
      HIV-1 isolates. Addition of infectious, T-tropic HIV-1 particles to TYMSTR/CD4
      expressing cells resulted in viral entry and proviral DNA formation. CONCLUSIONS:
      Our findings demonstrate that TYMSTR, in combination with CD4, mediates HIV-1
      fusion and entry. The high-level expression of TYMSTR in CD4(+) T lymphocytes and
      the selectivity of this receptor for T-tropic and M-tropic HIV-1 strains
      indicates that TYMSTR might function as HIV coreceptor at both early and late
      stages of infection.

PMID- 9285717
TI  - Rapid targeting of nuclear proteins to the cytoplasm.
AB  - BACKGROUND: The transcription factor NF-ATc plays a key role in the activation of
      many early immune response genes and is regulated by subcellular localization. NF
      ATc translocates from the cytoplasm to the nucleus in response to a rise in
      intracellular calcium, and immediately returns to the cytoplasm when
      intracellular calcium levels fall. The rapid nuclear exit of NF-ATc is thought to
      be one mechanism by which cells distinguish between sustained and transient
      calcium signals. RESULTS: To study the nuclear export of NF-ATc, we have
      developed a general, non-invasive assay for the identification and study of
      nuclear export signals (NESs). The NES is defined by its ability to translocate a
      protein from the nucleus to the cytoplasm when the two are tethered by a membrane
      permeable ligand. This procedure has allowed us to identify a NES within NF-ATc
      that functions in concert with a glycogen synthase kinase-regulated process to
      direct the rapid nuclear exit of NF-ATc. CONCLUSIONS: The rapid nuclear export of
      NF-ATc via its NES and a glycogen synthase kinase-regulated event may be an
      important mechanism for insulating cells from transient spikes in intracellular
      calcium which might otherwise lead to inappropriate activation. The assay we have
      developed allows the rapid identification of NESs and can be used as a general
      method for the inducible cytoplasmic export of nuclear proteins.

PMID- 9285718
TI  - Levels of categorization in visual recognition studied using functional magnetic
      resonance imaging.
AB  - BACKGROUND: Recent functional neuroimaging results implicate part of the ventral
      temporal lobe of the brain in face recognition, and have, together with
      neurophysiological findings, been used as evidence for a face-specific neural
      module in the brain. Experimental designs, however, have often failed to
      distinguish between the class of the object used as the stimulus (face or non
      face) and the level of categorization at which the stimulus is recognized (the
      'basic' level, such as 'bird', at which familiar objects are first recognized, or
      more subordinate levels - 'sparrow', for example - which require additional
      perceptual processing). We have used echo-planar functional magnetic resonance
      imaging to compare brain activation for the matching of non-face objects with
      subordinate-level and basic-level descriptors. RESULTS: The additional visual
      processing required to verify the subordinate level of a picture over its basic
      level was associated with activation of the fusiform and inferior temporal gyri
      (FIT) as well as the temporal poles. These areas correspond closely to those
      previously implicated in the processing of facial images. CONCLUSIONS: Our
      results indicate that areas of the ventral visual pathway that have been
      associated with face recognition are sensitive to manipulations of the
      categorization level of non-face objects. This idea offers an alternative to the
      dominant view that FIT may be organized according to conceptual categories, and
      our results establish the importance of manipulating task requirements when
      evaluating a 'neural module' hypothesis.

PMID- 9285719
TI  - Thymocytes in Thy-1-/- mice show augmented TCR signaling and impaired
      differentiation.
AB  - Thy-1, a single variable-like immunoglobulin superfamily domain anchored in the
      plasma membrane by a glycosyl phosphaditylinositol tail [1], is a major surface
      glycoprotein in adult mammalian neurons and rodent thymocytes [2]; the function
      of Thy-1 has remained enigmatic since its discovery [3]. Studies in vitro have
      implicated Thy-1 in homotypic and heterotypic cell-cell interactions [2,4].
      Ligation of Thy-1 initiates transmembrane signaling pathways that lead to diverse
      physiological outcomes in different cells [2,5-7]. In rodents, Thy-1 is highly
      expressed on the surface of CD4+CD8+ double-positive immature thymocytes and
      downregulated in mature T cells. Here, we report that thymocytes from Thy-1-/-
      mice [8] had altered cell-cell contacts, and hyperresponsiveness to T-cell
      receptor (TCR) triggering as demonstrated by the heightened activation of p56lck,
      phosphorylation of TCR subunits, Ca2+ fluxes and cell proliferation. Thy-1-/-
      thymocytes exhibited impaired maturation from the double positive to single
      positive stage of thymocyte development, possibly due to inappropriate negative
      selection, and were prone to T lymphomas in aged mice. These observations
      indicate that Thy-1 negatively regulates TCR-mediated signaling and controls
      activation thresholds during thymocyte differentiation.

PMID- 9285720
TI  - S-Phase entry upon ectopic expression of G1 cyclin-dependent kinases in the
      absence of retinoblastoma protein phosphorylation.
AB  - In mammalian cells, the retinoblastoma protein (Rb) is thought to negatively
      regulate progression through the G1 phase of the cell cycle by its association
      with the transcription factor E2F [1-3]. Rb-E2F complexes suppress transcription
      of genes required for DNA synthesis ([4], reviewed in [3,5]), and the prevailing
      view is that phosphorylation of Rb by complexes of cyclin-dependent kinases
      (Cdks) and their regulatory cyclin subunits, and the subsequent release of active
      E2F, is required for S-phase entry [1-3]. This view is based, in part, on the
      fact that ectopic expression of cyclin-Cdks leads to Rb phosphorylation and that
      this modification correlates with S-phase entry [6-8]. In Drosophila, however,
      cyclin E expression can bypass a requirement for E2F, suggesting that cyclins may
      activate replication independently of the Rb/E2F pathway [9]. We sought to
      examine whether Rb phosphorylation is a prerequisite for S-phase entry in Rb
      deficient SAOS-2 osteosarcoma cells, using a commonly used cotransfection assay
      [6-8,10]. We find that a G1 arrest in SAOS-2 cells mediated by an Rb mutant
      lacking all 14 consensus Cdk phosphorylation sites is bypassed by coexpressing G1
      specific E-type or D-type cyclin-Cdk complexes, and that injection of purified
      cyclin-Cdks during G1 accelerates S-phase entry. Our results indicate that Rb
      phosphorylation is not essential for S-phase entry when G1 cyclin-Cdks are
      overexpressed, and that other substrates of these kinases can be rate-limiting
      for the G1 to S-phase transition. These data also reveal that the SAOS-2
      cotransfection assay is complicated by Rb-independent effects of the coexpressed
      Cdks.

PMID- 9285721
TI  - Maintenance of neuroepithelial progenitor cells by Delta-Notch signalling in the
      embryonic chick retina.
AB  - BACKGROUND: Neurons of the vertebrate central nervous system (CNS) are generated
      sequentially over a prolonged period from dividing neuroepithelial progenitor
      cells. Some cells in the progenitor cell population continue to proliferate while
      others stop dividing and differentiate as neurons. The mechanism that maintains
      the balance between these two behaviours is not known, although previous work has
      implicated Delta-Notch signalling in the process. RESULTS: In normal development,
      the proliferative layer of the neuroepithelium includes both nascent neurons that
      transiently express Delta-1 (Dl1), and progenitor cells that do not. Using
      retrovirus-mediated gene misexpression in the embryonic chick retina, we show
      that where progenitor cells are exposed to Dl1 signalling, they are prevented
      from embarking on neuronal differentiation. A converse effect is seen in cells
      expressing a dominant-negative form of Dl1, Dl1(dn), which we show renders
      expressing cells deaf to inhibitory signals from their neighbours. In a
      multicellular patch of neuroepithelium expressing Dl1(dn), essentially all
      progenitors stop dividing and differentiate prematurely as neurons, which can be
      of diverse types. Thus, Delta-Notch signalling controls a cell's choice between
      remaining as a progenitor and differentiating as a neuron. CONCLUSIONS: Nascent
      retinal neurons, by expressing Dl1, deliver lateral inhibition to neighbouring
      progenitors; this signal is essential to prevent progenitors from entering the
      neuronal differentiation pathway. Lateral inhibition serves the key function of
      maintaining a balanced mixture of dividing progenitors and differentiating
      progeny. We propose that the same mechanism operates throughout the vertebrate
      CNS, enabling large numbers of neurons to be produced sequentially and adopt
      different characters in response to a variety of signals. A similar mechanism of
      lateral inhibition, mediated by Delta and Notch proteins, may regulate stem-cell
      function in other tissues.

PMID- 9285722
TI  - Essential functions of ezrin in maintenance of cell shape and lamellipodial
      extension in normal and transformed fibroblasts.
AB  - BACKGROUND: Changes in cell shape and motility are important manifestations of
      oncogenic transformation, but the mechanisms underlying these changes and key
      effector molecules in the cytoskeleton remain unknown. The Fos oncogene induces
      expression of ezrin, the founder member of the ezrin/radixin/moesin (ERM) protein
      family, but not expression of the related ERM proteins, suggesting that ezrin has
      a distinct role in cell transformation. ERM proteins have been suggested to link
      the plasma membrane to the actin-based cytoskeleton and are substrates and
      anchoring sites for a variety of protein kinases. Here, we examined the role of
      ezrin in cellular transformation. RESULTS: Fos-mediated transformation of Rat-1
      fibroblasts resulted in an increased expression and hyperphosphorylation of
      ezrin, and a concomitant increased association of ezrin with the cortical
      cytoskeleton. We tagged ezrin with green fluorescent protein and examined its
      distribution in normal and Fos-transformed fibroblasts: ezrin was concentrated at
      the leading edge of extending pseudopodia of Fos-transformed Rat-1 cells, and was
      mainly cytosolic in normal Rat-1 cells. Functional ablation of ezrin by micro
      CALI (chromophore-assisted laser inactivation) blocked plasma-membrane ruffling
      and motility of Fos-transformed fibroblasts. Ablation of ezrin in normal Rat-1
      cells caused a marked collapse of the leading edge of the cell. CONCLUSIONS:
      Ezrin plays an important role in pseudopodial extension in Fos-transformed Rat-1
      fibroblasts, and maintains cell shape in normal Rat-1 cells. The increased
      expression, hyperphosphorylation and subcellular redistribution of ezrin upon
      fibroblast transformation coupled with its roles in cell shape and motility
      suggest a critical role for ezrin in oncogenic transformation.

PMID- 9285723
TI  - High incidence of spontaneous and chemically induced liver tumors in mice
      deficient for connexin32.
AB  - Connexins are subunits of gap junction channels, which mediate the direct
      transfer of ions, second messenger molecules and other metabolites between
      contacting cells. Gap junctions are thought to be involved in tissue homeostasis,
      embryonic development and the control of cell proliferation [1,2]. It has also
      been suggested that the loss of intercellular communication via gap junctions may
      contribute to multistage carcinogenesis [3-5]. We have previously shown that
      transgenic mice that lack connexin32 (Cx32), the major gap junction protein
      expressed in hepatocytes, express lower levels of a second hepatic gap junction
      protein, Cx26, suggesting that Cx32 has a stabilizing effect on Cx26 [6]. Here,
      we report that male and female one-year-old mice deficient for Cx32 had 25-fold
      more and 8-fold more spontaneous liver tumors than wild-type mice, respectively.
      Incorporation of bromodeoxyuridine (BrdU) into the liver was higher for Cx32
      deficient mice than for wild-type mice, suggesting that their hepatocyte
      proliferation rate was higher. Furthermore, intraperitoneal injection, two weeks
      after birth, of the carcinogen diethylnitrosamine (DEN) led, after one year, both
      to more liver tumors in Cx32-deficient mice than in controls, and to accelerated
      tumor growth. Loss of Cx32 protein from hepatic gap junctions is therefore likely
      to cause enhanced clonal survival and expansion of mutated ('initiated') cells,
      which results in a higher susceptibility to hepatic tumors. Our results
      demonstrate that functional gap junctions inhibit the development of spontaneous
      and chemically induced tumors in mouse liver.

PMID- 9285724
TI  - Activin has direct long-range signalling activity and can form a concentration
      gradient by diffusion.
AB  - BACKGROUND: Activin has strong mesoderm-inducing properties in the early Xenopus
      embryo, and has a long-range signalling activity that activates genes in cells
      distant from a source in a concentration-dependent way. It has not yet been
      established what mechanism of signal transmission accounts for this and other
      examples of long-range signalling in vertebrates. Nor is it known whether activin
      itself acts on distant cells or whether other kinds of molecules are used for
      long-range signalling. Here we have used a well characterised model system,
      involving animal caps of Xenopus blastulae treated with activin or transforming
      growth factor beta, to analyze some fundamental properties of long-range
      signalling and of the formation of a morphogen gradient. RESULTS: We find that
      cells distant from the source of activin require functional activin receptors to
      activate Xbrachyury, a result suggesting that activin itself acts directly on
      distant cells and that other secondary signalling molecules are not required. We
      also find that the signals can be transmitted across a tissue that cannot respond
      to it; this argues against a relay process. We provide direct evidence that
      labelled activin forms a concentration gradient emanating from its source and
      extending to the distant cells that express Xbrachyury. Lastly, we show that
      there is no inherent polarity in the responding tissue that influences either the
      direction or rate of signalling. CONCLUSIONS: The long-range signalling mechanism
      by which activin initiates the transcription of genes in a concentration
      dependent manner depends on a process of rapid diffusion and the establishment of
      an activin gradient across the tissue. It cannot be explained by a relay or wave
      propagation mechanism. Activin itself is the signalling molecule to which distant
      cells respond.

PMID- 9285725
TI  - TRICK2, a new alternatively spliced receptor that transduces the cytotoxic signal
      from TRAIL.
AB  - A subset of the tumour necrosis factor (TNF) receptor family contain a conserved
      intracellular motif, the death domain. Engagement of these receptors by their
      respective ligands initiates a signalling cascade that rapidly leads to cell
      death by apoptosis. We have cloned a new member of this family, TRICK2, the TRAIL
      (TNF-related apoptosis-inducing ligand) receptor inducer of cell killing 2.
      TRICK2 is expressed in a number of cell types, and to particularly high levels in
      lymphocytes and spleen. Two isoforms of the TRICK2 mRNA are generated by
      alternative pre-mRNA splicing and differ by a 29 amino-acid extension to the
      extracellular domain. Overexpression of TRICK2 rapidly induced apoptosis in 293T
      cells; this induction was dependent upon the presence of the death domain of
      TRICK2. Using a soluble molecule containing the TRICK2 extracellular domain, we
      demonstrated that TRICK2, like DR4 [1], is a receptor for TRAIL/APO-2L [2,3] and
      could inhibit TRAIL-induced killing of lymphocyte lines, such as the Jurkat T
      cell line. TRAIL is upregulated upon lymphocyte activation, as is the intensively
      studied ligand for Fas, FasL [4]. TRAIL and its receptors might therefore provide
      another system for the regulation of lymphocyte selection and proliferation, as
      well as providing an additional weapon in the armoury of cytotoxic lymphocytes.

PMID- 9285726
TI  - Molecular dynamics simulations.

PMID- 9285728
TI  - Possible mechanism for the generation of the HIV-1-resistant form of the CCR5
      delta32 mutant chemokine receptor.

PMID- 9285733
TI  - Childhood moyamoya disease: hemodynamic MRI.
AB  - BACKGROUND: Childhood moyamoya disease is a rare progressive cerebrovascular
      disease. OBJECTIVE: To evaluate cerebral hemodynamics using dynamic Gd-DTPA
      enhanced imaging in children with moyamoya disease. MATERIALS AND METHODS: Eight
      children (2-11 years of age) with the clinical and angiographic findings typical
      of moyamoya disease, before and/or after surgical intervention (pial
      synangiosis), underwent conventional MR imaging (MRI) and hemodynamic MR imaging
      (HMRI). HMRI used a spoiled gradient-echo with low flip angle (10 deg) and long
      TE (TR/TE = 24/15 ms) to minimize T 1 effects and emphasize T 2* weighting. Raw
      and calculated hemodynamic images were reviewed. Three-dimensional time-of-flight
      MR angiography (MRA) and perfusion brain single photon emission computed
      tomography (SPECT) were also performed. RESULTS: Abnormal hemodynamic maps
      resulting from vascular stenosis or occlusion and basal collaterals were observed
      in six patient studies. HMRI depicted perfusion dynamics of affected
      cerebrovascular territories, detected cortical perfusion deficits, and
      complemented conventional MRI and MRA. HMRI findings were consistent with those
      of catheter angiography and perfusion SPECT. CONCLUSION: Our preliminary
      experience suggests that HMRI may be of value in the preoperative and
      postoperative evaluation of surgical interventions in moyamoya disease.

PMID- 9285734
TI  - Syringomyelia in mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome): imaging
      findings following bone marrow transplantation.
AB  - We present the imaging findings in a patient with mucopolysaccharidosis (MPS)
      type VI (Maroteaux-Lamy syndrome) who developed holocord syringomyelia. This
      represents the only reported case of syrinx formation in a child with MPS VI.
      Clinical, neurologic and spinal magnetic resonance imaging findings are
      presented. The patient has maintained a stable clinical and neurologic course
      over the period following allogeneic bone marrow transplant.

PMID- 9285735
TI  - Cranial ultrasound and CT findings in infants with hypernatremic dehydration.
AB  - We present two newborn infants with hypernatremic dehydration with central
      nervous system (CNS) involvement. Both patients showed similar imaging findings,
      demonstrating generalized brain parenchymal abnormality and multifocal areas of
      hemorrhage or hemorrhagic infarction. These findings are compatible with
      previously described CNS pathologic findings in hypernatremia.

PMID- 9285737
TI  - Congenital ganglioglioma: report of a case with an unusual imaging appearance.
AB  - A newborn presented with a cerebral ganglioglioma. This is a rare diagnosis in a
      neonate. The imaging appearance (hyperdense on CT, hyperintense on T1-weighted
      and hypointense on T2-weighted MRI) is very unusual for this type of tumor.

PMID- 9285736
TI  - Comparison of intracranial computed tomographic (CT) findings in pediatric
      abusive and accidental head trauma.
AB  - BACKGROUND: Child abuse specialists rely heavily on diagnostic neuroimaging.
      OBJECTIVES: Study objectives were: (1) to compare the frequencies of six specific
      intracranial CT abnormalities in accidental and non-accidental pediatric head
      trauma, and (2) to assess interobserver agreement regarding these CT findings.
      MATERIALS AND METHODS: Three pediatric radiologists blindly and independently
      reviewed cranial CT scans of pediatric patients who sustained closed head trauma
      between 1991 and 1994. All patients were less than 4 years of age. Study cases
      included thirty-nine (50 %) with non-accidental head trauma and thirty-nine (50
      %) with accidental head trauma. Each scan was evaluated for the presence or
      absence of the following six intracranial findings: (1) interhemispheric falx
      hemorrhage, (2) subdural hemorrhage, (3) large (non-acute) extra-axial fluid, (4)
      basal ganglia edema, (5) posterior fossa hemorrhage, and (6) frontal-parietal
      shearing tear(s). Interobserver agreement was calculated as the percentage of
      total cases in which all reviewers agreed a specific CT finding was present or
      absent. Diagnosis required independent agreement by all three pediatric
      radiologists. The frequencies of these six intracranial CT abnormalities were
      compared between the two study groups by Chi-square analysis and Fisher's exact
      test. RESULTS: Interobserver agreement between radiologists was greater than 80 %
      for all lesions evaluated, with the exception of frontal-parietal shearing
      tear(s). Interhemispheric falx hemorrhage, subdural hemorrhage, large (non-acute)
      extra-axial fluid, and basal ganglia edema were discovered significantly more
      frequently in non-accidental trauma (P </= .05). CONCLUSION: Although not
      specific for child abuse, discovery of these intracranial CT abnormalities in
      young patients should prompt careful evaluation of family and injury
      circumstances for indicators of non-accidental trauma.

PMID- 9285738
TI  - Ethnic factors in the variability of primary vesico-ureteral reflux with age.
AB  - OBJECTIVE: To determine any ethnic difference in the rate of spontaneous decrease
      in the incidence of primary vesico-ureteral reflux (VUR). MATERIALS AND METHODS:
      Voiding cystourethrograms on 738 patients with urinary tract infection were
      reviewed, and the incidence of primary vesico-urethral reflux was correlated with
      age, gender and ethnic origin. RESULTS: There was a gradual decrease in the
      incidence of primary VUR in whites between 0-10 years, while the incidence of
      primary VUR in blacks was very low and remained the same. After 10 years of age,
      no difference was present. CONCLUSION: The possibility of delayed maturation of
      the antireflux mechanism in whites is considered as a possible explanation, and
      the possibility of an ethnic basis for this is suggested.

PMID- 9285739
TI  - Pseudotumoral sarcoid granulomatous nephritis in a child: case presentation with
      sonographic and CT findings.
AB  - Granulomatous nephritis with renal masses is a very uncommon complication of
      sarcoidosis. Renal sonography in a patient with pathologically proven
      granulomatous nephritis demonstrated echogenic masses. CT demonstrated low
      density lesions with mottled contrast enhancement.

PMID- 9285740
TI  - Primary chylous vaginal discharge in a 9-year-old girl: CT-lymphangiogram and MR
      appearance.
AB  - Chylous reflux is a manifestation of primary or secondary lymphatic obstruction.
      Primary lymphatic obstruction is defined as lymphangiectasia and incompetency of
      lymphatic valves without an underlying cause. Lymphangiectasia resulting from
      trauma, neoplasm, irradiation, or inflammation characterizes secondary lymphatic
      obstruction. Leakage of chyle into the uterus, vagina, bladder, or rectum can
      occur with either primary or secondary lymphatic obstruction. We report a patient
      with chylous vaginal discharge, a rare presentation of primary chylous reflux
      syndrome. CT-lymphangiography and magnetic resonance imaging clearly depicted
      this disorder. To our knowledge, only 20 cases of chylous vaginal discharge have
      been reported previously; chylous vaginal drainage occurred in the absence of
      chylous uterine reflux in only three. Although this is a rare anomaly, chylous
      reflux should be considered in a child with chronic vaginal discharge and lower
      extremity swelling.

PMID- 9285741
TI  - Bilateral cystic neuroblastoma: imaging features and differential diagnoses.
AB  - Neuroblastoma is one of the most common malignant tumors of childhood, with 40 %
      arising in the adrenal glands. Bilateral adrenal involvement from synchronous
      development or metastatic spread of the tumor is seen in less than 10 % of
      children with neuroblastoma [1]. Neuroblastoma rarely presents as a cystic
      suprarenal mass that is difficult to differentiate from adrenal hemorrhage,
      extralobar sequestration, or dilated upper-pole renal calyces. To our knowledge,
      bilateral cystic neuroblastoma has not been previously reported. We present a
      case of bilateral cystic adrenal neuroblastoma to demonstrate the imaging
      features of this unusual entity, and to expand the differential diagnosis of
      bilateral cystic suprarenal masses in an infant.

PMID- 9285742
TI  - Pulmonary artery pseudoaneurysm after percutaneous transluminal angioplasty in a
      pediatric patient.
AB  - We report a case of a 4-year-old boy with tetralogy of Fallot, pulmonary atresia,
      and hypoplastic pulmonary arteries who presented with mild hemoptysis and upper
      respiratory infection 3 weeks following percutaneous transluminal angioplasty for
      pulmonary artery stenosis. While pneumonia was initially suggested on early plain
      radiographs of the chest, a large pseudoaneurysm of a right lower lobe pulmonary
      artery branch was subsequently diagnosed with CT and angiography.

PMID- 9285743
TI  - Hemophilia presenting in an infant as a radial artery pseudoaneurysm following
      arterial puncture.
AB  - The case presented is of an infant who developed a radial artery pseudoaneurysm
      following arterial puncture and was subsequently diagnosed with hemophilia. A
      discussion of radial artery pseudoaneurysms follows.

PMID- 9285744
TI  - MRI demonstration of occult purely chondral fractures of the tibia: a potential
      mimic of meniscal tears.
AB  - We report the case of a 12-year-old boy with bilateral, purely chondral fractures
      of the tibia. The patient had Crohn's disease treated with systemic
      corticosteroids. MR images of the knee were initially interpreted to show a
      bucket-handle tear of the lateral meniscus. However, arthroscopic evaluation
      revealed purely chondral fractures of the tibial plateau without meniscal damage.
      Re-evaluation of the MR study identified the chondral fracture of the lateral
      tibial articular cartilage detected arthroscopically. This purely chondral
      fracture of the tibial plateau represented a rare finding in the symptomatic knee
      that mimicked a meniscal tear by history, physical exam, and MR imaging.

PMID- 9285746
TI  - Commentary: oral contrast medium administration for abdominal CT - reevaluating
      the benefits and disadvantages in the pediatric patient.

PMID- 9285745
TI  - Aneurysmal bone cyst secondary to infantile cartilaginous hamartoma of rib.
AB  - We report the first case, in a 4-month-old girl, of an aneurysmal bone cyst
      secondary to infantile cartilaginous hamartoma of the rib. Infantile
      cartilaginous hamartoma of the rib (benign mesenchymoma) is a large, expansile
      tumour that is characterised by cartilaginous, vascular and primitive-appearing
      stromal and mesenchymal elements. Most cases are diagnosed at less than 1 year of
      age and may even be congenital. Aneurysmal bone cyst may be a secondary lesion to
      pre-existing tumours such as giant cell tumours, osteoblastomas, angiomas and
      chondroblastomas. This unique case is presented with radiological and
      pathological findings.

PMID- 9285747
TI  - Ringed esophagus (feline esophagus) in childhood.
AB  - Feline esophagus is a term describing a specific radiological and endoscopic
      appearance of the esophagus that is attributed to chronic esophagitis. To date
      only one report has described this appearance in childhood. We present a
      histologically documented case of this entity including follow-up studies after
      therapy for esophagitis.

PMID- 9285748
TI  - Hangman's fracture in an abused infant: imaging features.
AB  - A case of a hangman's fracture in an abused infant is presented. The imaging
      features are illustrated and a mechanism of injury is suggested.

PMID- 9285750
TI  - Fetal varicella syndrome: association with multiple hepatic calcifications and
      intestinal atresia.

PMID- 9285749
TI  - Derek Harwood-Nash obituaries.

PMID- 9285751
TI  - Telescoped jejunum: a complication of Dobhoff catheter placement.

PMID- 9285771
TI  - Coregulation of beta-galactoside uptake and hydrolysis by the hyperthermophilic
      bacterium Thermotoga neapolitana
AB  - Regulation of the beta-galactoside transport system in response to growth
      substrates in the extremely thermophilic anaerobic bacterium Thermotoga
      neapolitana was studied with the nonmetabolizable analog methyl-beta-D
      thiogalactopyranoside (TMG) as the transport substrate. T. neapolitana cells
      grown on galactose or lactose accumulated TMG against a concentration gradient in
      an intracellular free sugar pool that was exchangeable with external galactose or
      lactose and showed induced levels of beta-galactosidase. Cells grown on glucose,
      maltose, or galactose plus glucose showed no capacity to accumulate TMG, though
      these cells carried out active transport of the nonmetabolizable glucose analog 2
      deoxy-D-glucose. Glucose neither inhibited TMG uptake nor caused efflux of
      preaccumulated TMG; rather, glucose promoted TMG uptake by supplying metabolic
      energy. These data show that beta-D-galactosides are taken up by T. neapolitana
      via an active transport system that can be induced by galactose or lactose and
      repressed by glucose but which is not inhibited by glucose. Thus, the phenomenon
      of catabolite repression is present in T. neapolitana with respect to systems
      catalyzing both the transport and hydrolysis of beta-D-galactosides, but inducer
      exclusion and inducer expulsion, mechanisms that regulate permease activity, are
      not present. Regulation is manifest at the level of synthesis of the beta
      galactoside transport system but not in the activity of the system.

PMID- 9285772
TI  - The glucose transport system of the hyperthermophilic anaerobic bacterium
      Thermotoga neapolitana
AB  - The glucose transport system of the extremely thermophilic anaerobic bacterium
      Thermotoga neapolitana was studied with the nonmetabolizable glucose analog 2
      deoxy-D-glucose (2-DOG). T. neapolitana accumulated 2-DOG against a concentration
      gradient in an intracellular free sugar pool that was exchangeable with external
      source of energy, such as pyruvate, and was inhibited by arsenate and gramicidin
      D. There was no phosphoenolpyruvate-dependent phosphorylation of glucose, 2-DOG,
      or fructose by cell extracts or toluene-treated cells, indicating the absence of
      a phosphoenolpyruvate:sugar phosphotransferase system. These data indicate that D
      glucose is taken up by T. neapolitana via an active transport system that is
      energized by an ion gradient generated by ATP, derived from substrate-level
      phosphorylation.

PMID- 9285773
TI  - Two roles for mu-crystallin: a lens structural protein in diurnal marsupials and
      a possible enzyme in mammalian retinas.
AB  - PURPOSE: micro-Crystallin is a major taxon-specific lens protein in some
      marsupials. Like other taxon-specific crystallins, it probably has another, non
      crystallin role. Here we examine the distribution of mu-crystallin among species
      and its localization in the eye in placental mammals. We also compare its
      sequence and ligand binding characteristics with those of known enzymes. METHODS:
      An antibody (Mup1) was raised against a conserved 21 residue peptide of tammar
      wallaby mu-crystallin. This was used to detect mu-crystallin immunoreactivity in
      lens extracts of several species and in the tissues of rat and bovine eyes. PCR
      methods were used to complete the cDNA sequence of human mu-crystallin. The
      ability of kangaroo mu-crystallin to bind enzymatic cofactors was tested by blue
      sepharose chromatography. RESULTS: Using Mup1, abundant mu-crystallin was
      observed in soluble whole lens extracts of diurnal Australian marsupials.
      Although abundant micro-crystallin was not detectable in whole lens of nocturnal
      marsupials, other mammals or a bird, lower levels of immunoreactivity were
      detectable in lens epithelium, retinal pigment epithelium and, particularly,
      retina of bovine eye. In rat eye the highest levels of Mup1 reactivity were found
      in retinal photoreceptors. Sequence comparisons of human and kangaroo mu
      crystallin reveal a superfamily relationship with enzymes of glutamate and
      ornithine metabolism. Co-factor binding studies indicate that mu-crystallin, like
      related glutamyl-tRNA reductases, binds NADPH. CONCLUSIONS: These results suggest
      that mu-crystallin is a normal component of retina and other tissues which
      underwent gene recruitment to gain an additional structural role in the lens
      during the evolution of diurnal marsupial species. mu-crystallin may be an
      enzyme, possibly of amino acid metabolism, with particular importance for
      photoreceptors.

PMID- 9285774
TI  - Characterization of susceptible chiasma configurations that increase the risk for
      maternal nondisjunction of chromosome 21.
AB  - Recent studies of trisomy 21 have shown that altered levels of recombination are
      associated with maternal non-disjunction occurring at both meiosis I (MI) and
      meiosis II (MII). To comprehend better the association of recombination with
      nondisjunction, an understanding of the pattern of meiotic exchange, i.e. the
      exchange of genetic material at the four-strand stage during prophase, is
      required. We examined this underlying exchange pattern to determine if specific
      meiotic configurations are associated with a higher risk of non-disjunction than
      others. We examined the crossover frequencies of chromosome 21 for three
      populations: (i) normal female meiotic events; (ii) meiotic events leading to MI
      non-disjunction; and (iii) those leading to MII non-disjunction. From these
      crossover frequencies, we estimated the array of meiotic tetrads that produced
      the observed crossovers. Using this approach, we found that nearly one-half of MI
      errors were estimated to be achiasmate. The majority of the remaining MI
      bivalents had exchanges that clustered at the telomere. In contrast, exchanges
      occurring among MII cases clustered at the pericentromeric region of the
      chromosome. Unlike the single exchange distributions, double exchanges from the
      non-disjoined populations seemed to approximate the distribution in the normal
      population. These data suggest that the location of certain exchanges makes a
      tetrad susceptible to non-disjunction. Specifically, this susceptibility is
      associated with the distance between the centromere and closest exchange. This
      result challenges the widely held concept that events occurring at MII are
      largely independent of events occurring at MI, and suggests that all non
      disjunction events may be initiated during MI and simply resolved at either of
      the two meiotic stages.

PMID- 9285775
TI  - A susceptibility locus for early-onset non-insulin dependent (type 2) diabetes
      mellitus maps to chromosome 20q, proximal to the phosphoenolpyruvate
      carboxykinase gene.
AB  - Several candidate genes for non-insulin-dependent diabetes mellitus (NIDDM) map
      on chromosome 20, including the phosphoenolpyruvate carboxykinase gene (PCK1) and
      one of the maturity onset diabetes of the young genes (MODY1). Thus, we have
      investigated the entire long arm of chromosome 20. Linkage analyses were
      conducted in a total sample of 148 NIDDM families (301 NIDDM sib pairs) and in a
      subset of 42 early onset NIDDM families, where genetic components are likely to
      play a more important role (55 NIDDM sib pairs diagnosed at or before 45 years of
      age), using 10 highly polymorphic markers with an average map density of 7.5 cM.
      Using affected sib pair methods (two-point linkage and multipoint linkage
      analyses), significant results were obtained with the 20q13 region, in the
      vicinity of the PCK1 locus, only in the subset of 55 early onset NIDDM sib pairs
      (multipoint MLS = 2.74, P = 0.0004; MLS = 2.34, P = 0.0009 when using a
      conservative weighting procedure). Moreover, another region spanning the
      ribophorin II (RPNII, phospholipase C (PLC1) and adenosine deaminase (ADA) loci
      suggested linkage with NIDDM (multipoint MLS of 1.81 in all NIDDM sib pairs, P =
      0.003; MLS = 1.31, P = 0.012 when using a conservative weighting procedure).
      Whereas our study suggests the location of a susceptibility locus for early onset
      NIDDM in the PCK1 gene region, further investigation in larger data sets is
      required to confirm these results and assess the role of other regions on
      chromosome 20q in human NIDDM.

PMID- 9285776
TI  - Mutations in the TSC2 gene: analysis of the complete coding sequence using the
      protein truncation test (PTT).
AB  - Mutations in the TSC2 gene on chromosome 16p13.3 are responsible for
      approximately 50% of familial tuberous sclerosis (TSC). The gene has 41 small
      exons spanning 45 kb of genomic DNA and encoding a 5.5 kb mRNA. Large germline
      deletions of TSC2 occur in <5% of cases, and a number of small intragenic
      mutations have been described. We analysed mRNA from 18 unrelated cases of TSC
      for TSC2 mutations using the protein truncation test (PTT). Three cases were
      predicted to be TSC2 mutations on the basis of linkage analysis or because a
      hamartoma from the patient showed loss of heterozygosity for 16p13.3 markers.
      Three overlapping PCR products, covering the complete coding sequence of mRNA,
      were generated from lymphoblastoid cell lines, translated into 35S-methionine
      labelled protein, and analysed by SDS-PAGE. PCR products showing PTT shifts were
      directly sequenced, and mutations confirmed by restriction enzyme digestion where
      possible. Six PTT shifts were identified. Five of these were caused by mutations
      predicted to produce a truncated protein: (i) a sporadic case showed a 32 bp
      deletion in exon 11, and a mutant mRNA without exon 11 was produced; the normal
      exon 10 was also spliced out; (ii) a sporadic case had a 1 bp deletion in exon 12
      (1634delT); (iii) a TSC2-linked mother and daughter pair had a G-->T transversion
      in exon 23 (G2715T) introducing a cryptic splice site causing a 29 bp truncation
      of mRNA from exon 23; (iv) a sporadic case showed a 2 bp deletion in exon 36; (v)
      a sporadic case showed a 1 bp insertion disrupting the donor splice site of exon
      37 (5007+2insA), resulting in the use of an upstream exonic cryptic splice site
      to cause a 29 bp truncation of mRNA from exon 37. In one case, the PTT shift was
      explained by in-frame splicing out of exon 10, in the presence of a normal exon
      10 genomic sequence. Alternative splicing of exon 10 of the TSC2 gene may be a
      normal variant. Three 3rd base substitution polymorphisms were also detected
      during direct sequencing of PCR products. Confirmed mutations were identified in
      28% of the families studied and on the assumption that half of the sporadic cases
      should have TSC2 mutations, a crude estimate of the detection rate would be 60%.
      This compares favourably with other screening methods used for TSC2, notably
      SSCP, and since PTT involves much less work it may be the method of choice.

PMID- 9285777
TI  - Strategems in vitro for gene therapies directed to dominant mutations.
AB  - A major difficulty associated with the design of gene therapies for autosomal
      dominant diseases is the immense intragenic heterogeneity often encountered in
      such conditions. In order to overcome such difficulties we have designed, and
      evaluated in vitro, three strategies which avoid a requirement to target
      individual mutations for genetic suppression. In the first, normal and mutant
      alleles are suppressed by targeting sequences in transcribed but untranslated
      regions of transcript (UTRs), enabling introduction of a replacement gene with
      the correct coding sequencing but altered UTRs to prevent suppression. A second
      approach involves suppression in coding sequence and concurrent introduction of a
      replacement gene by exploiting the degeneracy of the genetic code. A third
      strategy utilises intragenic polymorphism to suppress the disease allele
      specifically, the advantage being that a proportion of patients with different
      disease mutations have the same polymorphism. These approaches provide a wider
      choice of target sequence than those directed to single disease mutations and are
      appropriate for many mutations within a given gene. General methods for
      suppression may be directed towards the primary defect or a secondary effect
      associated with the disease process, such as apoptosis. Three general methods
      targeting the primary defect which circumvent problems of allelic genetic
      heterogeneity are explored in vitro using hammerhead ribozymes designed to target
      transcripts from the rhodopsin, peripherin and collagen 1A1 and 1A2 genes,
      extensive genetic heterogeneity being a feature of associated disease
      pathologies.

PMID- 9285778
TI  - Characterization of a new BLM mutation associated with a topoisomerase II alpha
      defect in a patient with Bloom's syndrome.
AB  - Bloom's syndrome (BS), a human recessive disorder associated with an increased
      risk of malignancy, arises through mutations in both alleles of the BLM gene,
      which was recently identified as a member of the RecQ helicase family. BS cells
      are characterized by an increased rate of sister chromatid exchange (SCE).
      However, a subpopulation of lymphocytes exhibiting a normal level of SCE is
      observed in some patients. It has been proposed that reversion to a low-SCE
      phenotype involves an intragenic crossing over between the paternal and maternal
      BLM alleles, generating a wild-type allele. In this study we characterize a new
      BLM mutation in a BS patient leading to the replacement, in the C-terminal region
      of Blm, of a highly conserved cysteine by a phenylalanine in codon 1036.
      Moreover, our data show that this patient also inherited a BLM allele carrying a
      mutation affecting its expression and that a somatic intragenic crossing over was
      involved in reversion to the low-SCE phenotype. Further, we show that both
      topoisomerase II alpha mRNA and protein levels are decreased in the high-SCE
      cells derived from this patient, whereas they are normal in the corresponding low
      SCE cells. Altogether, our data led us to propose that besides its putative
      helicase activity, Blm could be involved in transcription regulation.

PMID- 9285779
TI  - High expression of naked plasmid DNA in muscles of young rodents.
AB  - There is a time window at 2 weeks of age for achieving very high levels of
      foreign gene expression from the intramuscular injection of naked plasmid DNA in
      mice and rats. The highest expression, over 1 microg of luciferase
      protein/muscle, was obtained in Balb/C mice using constructs containing the CMV
      promoter, a chimeric intron and the luc+ luciferase gene. Approximately 50% of
      the myofibers were intensely blue following the intramuscular injection of a beta
      galactosidase expression vector in 2 week old Balb/C mice. The effects of age,
      mouse strain and construct were multiplicative, resulting in >1000-fold greater
      luciferase and approximately 20-fold more beta-galactosidase-positive cells.
      These high levels of expression were unstable and were not observed in larger
      animals (dog, rhesus monkey). These results indicate that enormous levels of
      foreign gene expression can be obtained in muscle with naked DNA in vivo and will
      enable the temporary effects of gene function and expression in rodent muscle to
      be expeditiously studied.

PMID- 9285780
TI  - The preliminary transcript map of a human skeletal muscle.
AB  - By sequencing 11,405 individual expressed sequence tags (ESTs) from a cDNA
      library of a human skeletal muscle, we identified 1945 individual transcripts,
      725 of which showed no correspondence with known human genes. We report here the
      chromosomal localization of 267 of these, obtained by radiation hybrid (RH)
      mapping. The map position of additional 242 ESTs from the same library,
      corresponding to known human genes, is also reported. The resulting information
      provides a preliminary genomic transcriptional profile of a human muscle. Several
      genes occur in clusters on different chromosomes. Moreover, chromosomes 17, 19,
      21 and X appear to be significantly rich in muscle ESTs. By analysing several
      collections of ESTs from different tissues, we observed significant deviations in
      the distribution of ESTs by chromosome in fetal heart, adult brain and adult
      retina, supporting the hypothesis that a non-random localization of genes
      expressed in specific tissues might not be uncommon. The selective concentration
      of expressed genes in some chromosomes and in specific chromosomal subregions in
      a given tissue might reflect the existence of batteries of genes under the same
      control mechanisms, regulating tissue-specific gene expression.

PMID- 9285781
TI  - Functional correction of short-chain acyl-CoA dehydrogenase deficiency in
      transgenic mice: implications for gene therapy of human mitochondrial enzyme
      deficiencies.
AB  - We report the therapeutic effects of liver-specific expression of a short-chain
      acyl-CoA dehydrogenase (SCAD) transgene in the SCAD-deficient mouse model.
      Transgenic mice were produced with a rat albumin promoter/enhancer driving a
      mouse SCAD minigene (ALB-SCAD) on both the SCAD normal genetic background and a
      SCAD-deficient background. In three transgenic lines produced on the SCAD
      deficient background, recombinant SCAD activity and antigen in liver mitochondria
      were found up to 7-fold of normal control values. All three lines showed a
      markedly reduced organic aciduria and fatty liver, which are sensitive indicators
      of the metabolic abnormality seen in this disease found in children. We found no
      detrimental effects of high liver SCAD expression in transgenic mice on either
      background. These studies provide important basic and practical therapeutic
      information for the potential gene therapy of nuclear-encoded mitochondrial
      enzyme deficiencies, as well as insights into the mechanisms of the disease.

PMID- 9285782
TI  - Expression and kinetic characterization of methylmalonyl-CoA mutase from patients
      with the mut- phenotype: evidence for naturally occurring interallelic
      complementation.
AB  - L-Methylmalonyl-CoA mutase (MUT) is an adenosylcobalamin (AdoCbl)-requiring
      mitochondrial matrix enzyme that catalyzes the isomerization of L-methylmalonyl
      CoA to succinyl-CoA. Inherited defects in the gene encoding this enzyme result in
      the mut forms of methylmalonic acidemia. Expression of mature human MUT cDNA in
      Escherichia coli at a post-induction cultivation temperature of 12 degrees C,
      rather than 37 degrees C, led to the folding of the majority of the synthesized
      protein to a soluble form, with an activity of 0.2-0.3 U/mg protein in the cell
      free extract, 10-15 times higher than that in human liver homogenate. Six
      missense mutations, producing the amino acid changes G94V, Y231N, R369H, G623R,
      H678R and G717V, were detected in MUT cDNA of patients suffering from the mut-
      form of methylmalonic acidemia, resulting from defective AdoCbl binding. Two
      (G623R and G717V) had been reported in other patients. Three (G94V, Y231N and
      R369H) are the first changes in the NH2-terminal part of the enzyme reported to
      cause the mut- phenotype. Enzymes with the mutations were individually expressed,
      and their kinetic parameters were generally in accord with published biochemical
      data from extracts of fibroblasts from these patients. The mutations increased
      the K(m) for AdoCbl by 40- to 900-fold, while V(max) values varied from 0.2% to
      nearly 100% of that of wild-type protein. In one case of a doubly heterozygous
      cell line, however, neither of the constituent mutant enzymes had a K(m)
      corresponding to the lower of the two estimated from the extract data. This
      finding may reflect the natural occurrence of interallelic complementation in
      vivo in this cell line.

PMID- 9285783
TI  - The fragile X mental retardation protein is associated with poly(A)+ mRNA in
      actively translating polyribosomes.
AB  - The fragile X syndrome results from a transcriptional silencing of the FMR1 gene
      and the absence of its encoded protein. FMRP is a cytoplasmic RNA-binding
      protein, whose specific cellular function is still unknown. We present evidence
      that virtually all detectable cytoplasmic FMRP in mouse NIH 3T3 and human HeLa
      cells is found strictly in association with mRNA in actively translating
      polyribosomes. Furthermore, FMRP released from polyribosomes is associated with
      ribonucleoprotein complexes with sedimentation coefficients of 60-70S and
      selection on oligo(dT)-cellulose reveals that this association is specific to
      poly(A)-containing mRNPs. This association with actively translating
      polyribosomes is not affected by alteration of translational processes induced by
      serum stimulation and starvation in NIH 3T3 cells, suggesting that FMR1
      expression is not cell cycle regulated and that FMRP might have a house-keeping
      function. FXR2 protein, which is closely related to FMRP, is also detected
      associated with mRNPs in translating polyribosomes. The results strongly suggest
      that FMRP might be a mRNA chaperone interacting with mRNP complexes.

PMID- 9285784
TI  - An unusual pattern of mutation in the duplicated portion of PKD1 is revealed by
      use of a novel strategy for mutation detection.
AB  - The gene for the most common and severe form of autosomal dominant polycystic
      kidney disease, PKD1, encodes a 14 kb mRNA that is predicted to result in an
      integral membrane protein of 4302 amino acids. The major challenge faced by
      researchers attempting to complete mutation analysis of the PKD1 gene has been
      the presence of several homologous loci also located on chromosome 16. Because
      the sequence of PKD1 and its homologs is nearly identical in the 5' region of the
      gene, most traditional approaches to mutation analysis cannot distinguish
      sequence variants occurring uniquely in PKD1. Therefore, only a small number of
      mutations have been identified to date and these have all been found in the 3',
      unique portion of the gene. In order to begin analysis of the duplicated region
      of PKD1, we have devised a novel strategy that depends on long-range PCR and a
      single gene-specific primer from the unique region of the gene to amplify a PKD1
      specific template that spans exons 23-34. This 10 kb template, amplified from
      genomic DNA, can be employed for mutation analysis using a wide variety of
      sequence-based approaches. We have used our long-range PCR strategy to begin
      screening for sequence variants with heteroduplex analysis, and several affected
      individuals were discovered to have clusters of base pair substitutions in exons
      23 and 25. In two patients, these changes, identified in exon 23, would be
      predicted to result in multiple amino acid substitutions in a short stretch of
      the protein. This clustering of base pair substitutions is unusual and suggests
      that mutation may result from unique structural features of the PKD1 gene.

PMID- 9285785
TI  - Comparative analysis of the polycystic kidney disease 1 (PKD1) gene reveals an
      integral membrane glycoprotein with multiple evolutionary conserved domains.
AB  - PKD1 is the major locus of the common genetic disorder autosomal dominant
      polycystic kidney disease (ADPKD). Analysis of the predicted protein sequence of
      the human PKD1 gene, polycystin, shows a large molecule with a unique arrangement
      of extracellular domains and multiple putative transmembrane regions. The precise
      function of polycystin remains unclear with a paucity of mutations to define key
      structural and functional domains. To refine the structure of this protein we
      have cloned the genomic region encoding the Fugu PKD1 gene. Fugu PKD1 spans 36 kb
      of genomic DNA and has greater complexity with 54 exons compared with 46 in man.
      Comparative analysis of the predicted protein sequences shows a lower level of
      homology than in similar studies with identity of 40 and 59% similarity. However
      key structural motifs including leucine rich repeats (LRR), a C-type lectin and
      LDL-A like domains and 16 PKD repeats are maintained. A region of homology with
      the sea urchin REJ protein was also confirmed in Fugu but found to extend over
      1000 amino acids. Several highly conserved intra- and extra-cellular regions,
      with no known sequence homologies, that are likely to be of functional importance
      were detected. The likely structure of the membrane associated region has been
      refined with similarity to the PKD2 protein and voltage gated Ca2+ and Na+
      channels highlighted over part of this area. The overall protein structure has
      therefore been clarified and this comparative analysis derived structure will
      form the basis for the functional study of polycystin and its individual domains.

PMID- 9285786
TI  - Familial hypomagnesemia maps to chromosome 9q, not to the X chromosome: genetic
      linkage mapping and analysis of a balanced translocation breakpoint.
AB  - Familial hypomagnesemia with secondary hypocalcemia (HSH) (MIM 307600) was
      studied in three inbred Bedouin kindreds from Israel. The three kindreds, one
      extended and two nuclear families, contained 13 affected individuals, 11 males
      and two females. Assuming that the individuals affected with hypomagnesemia
      shared a chromosomal region inherited from a common ancestor, we used a DNA
      pooling strategy in a genome-wide search for loci which show homozygosity for
      shared alleles in affected individuals. DNA samples from affected individuals
      within a single kindred were pooled and used as the template for PCR
      amplification of short tandem repeat polymorphic markers (STRPs). Pooled DNA from
      unaffected siblings and parents were used as controls. A shift towards
      homozygosity was observed in the affected DNA pool compared with the control
      pools with D9S301 (GATA7D12). Genotyping of individual DNA samples with D9S301
      and several flanking markers confirmed linkage to chromosome 9 with maximum LOD
      scores of 3.4 (theta = 0.05), 3.7 (theta = 0) and 2.3 (theta = 0) for the three
      families. We have identified a 14 cM interval on chromosome 9 (9q12-9q22.2),
      flanked by proximal marker D9S1874 and distal marker D9S1807, within which all
      affected individuals from the three kindreds are homozygous for a shared
      haplotype. The disease segregates with a common affected haplotype in the three
      families, suggesting that hypomagnesemia is caused by a common ancestral mutation
      in these families. Although HSH has been previously reported to be X linked,
      these linkage data demonstrate that the disorder is an autosomal recessive
      disease in these kindreds. Mapping of a chromosomal breakpoint in a somatic cell
      line established from a patient with HSH and a balanced X;9 translocation placed
      the chromosomal breakpoint in a 500 kb region flanked by D9S1844 and D9S273.
      Identification of the gene responsible for hypomagnesemia will provide insight
      into the regulation of this essential cation.

PMID- 9285787
TI  - Characterization of mutations in the myotubularin gene in twenty six patients
      with X-linked myotubular myopathy.
AB  - A candidate gene, myotubularin, involved in the pathogenesis of X-linked
      myotubular myopathy (MTM1) was isolated recently. Mutations originally were
      identified in 12% of patients examined for 40% of the coding sequence, raising
      the possibility that additional genes could be responsible for a proportion of X
      linked cases. We report here the identification of mutations in 26 of 41
      independent male patients with muscle biopsy-proven MTM, by direct genomic
      sequencing of 92% of the known coding sequence of the myotubularin gene. Eighteen
      patients had point mutations, including one A/G transition found in four patients
      which alters a splice acceptor site in exon 12 and leads to a three amino acid
      insertion. Six patients had small deletions involving <6 bp, while two larger
      deletions encompassed two or six exons, respectively. No differences were noted
      among the types of mutations between familial and sporadic cases. However, all of
      the five patients with a mild phenotype had missense mutations. While 50% of the
      mutations were found in exons 4 and 12, and three distinct mutations were found
      in more than one patient, no single mutation accounted for more than 10% of the
      cases. The low frequency of large deletions and the varied mutations identified
      suggest that direct mutation screening for molecular diagnosis may require gene
      sequencing.

PMID- 9285788
TI  - Identification of a 14 kb deletion involving the promoter region of BRCA1 in a
      breast cancer family.
AB  - BRCA1 is a breast and ovarian cancer susceptibility gene. An inferred germline
      regulatory mutation was previously reported in the BRCA1-linked kindred K2035,
      based on the absence of transcripts from the BRCA1 allele associated with the
      cancer susceptibility haplotype. In this study, the promoter region of BRCA1 was
      examined in individuals from K2035 for evidence of a mutation which could halt
      transcription. Evaluation of a polymorphism located within intron 2 of BRCA1 gave
      results consistent with the presence of a large deletion in K2035 mutation
      carriers. Southern blot analysis identified unique restriction fragments which
      occurred as a result of a 14 kb deletion that removed both of BRCA1's
      transcription start sites (exons 1a and 1b) as well as exon 2. Sequencing
      indicated that unequal crossover between Alu repeats was the likely cause of the
      deletion. Similar deletions may be responsible for other reported inferred
      regulatory mutations, as well as unidentified mutations in families linked to
      BRCA1.

PMID- 9285790
TI  - Human renin binding protein: complete genomic sequence and association of an
      intronic T/C polymorphism with the prorenin level in males.
AB  - The role of renin binding protein (RnBP) in human (patho)physiology, despite its
      biochemical characterization, is as yet unclear. RnBP has been shown to bind and
      inactivate renin, a key player of the blood pressure regulating renin-angiotensin
      system. This renders the RnBP gene a promising candidate gene in human
      hypertension. Herein, a molecular genetic approach was employed to investigate if
      RnBP might affect renin, prorenin and/or blood pressure levels. Sequencing of the
      human Xq28 chromosomal region provided the precise chromosomal location and full
      genomic sequence of the RnBP gene. All 11 exons, adjacent intronic splice sites
      and the promoter region were sequenced in 20 patients with essential hypertension
      of early onset and possible X-linked inheritance and in four normotensive
      individuals. The only variant found was a single base exchange polymorphism 61
      base pairs upstream of the intron 6/exon 7 boundary (T61C). Several
      cardiovascular parameters, the renin, and prorenin levels and the T61C allele
      status were determined in 505 Caucasian individuals. Male individuals without
      medication who were hemizygous for the C allele were characterized by lower
      prorenin levels (196 +/- 15 versus 256 +/- 12 mU/l, P = 0.05) and a significantly
      higher renin/prorenin ratio (10.7 +/- 1.5 versus 7.7 +/- 0.3%, P = 0.002),
      whereas no variations in circulating renin, blood pressure, heart rate and left
      ventricular mass index were associated with the C allele. No significant
      association was observed in women. The data do not exclude a role of RnBP in
      essential hypertension. The complete genomic structure of the RnBP gene,
      including the identified repetitive sequence elements, provides an essential tool
      for further studies of the RnBP gene in hypertensive patients with a different
      genetic background.

PMID- 9285789
TI  - Huntingtin-associated protein 1 (HAP1) binds to a Trio-like polypeptide, with a
      rac1 guanine nucleotide exchange factor domain.
AB  - Huntington's disease (HD) occurs when the widely expressed protein huntingtin
      contains an expanded glutamine repeat. The selective degeneration and neuronal
      morphologic abnormalities of HD may involve interactions with proteins that bind
      to huntingtin, such as HAP1. The biological significance of this interaction is
      unclear because neither HAP1 nor huntingtin have significant homology to known
      proteins. Therefore, we sought to identify HAP1-binding proteins. Using the yeast
      two-hybrid system, we isolated a rat cDNA encoding part of a protein that
      interacts with HAP1, and we confirmed the specificity of this interaction using
      an in vitro protein-binding assay. We called the protein Duo because it is
      closely related to the human protein Trio but is shorter. Northern blot analysis
      indicates brain-specific expression of Duo. Human Duo contains a guanine
      nucleotide exchange factor (GEF) domain that is likely to be rac1-specific, a
      pleckstrin homology (PH) domain and spectrin-like repeat units. These data
      support the hypothesis that huntingtin is involved in vesicle trafficking and
      cytoskeletal functions, and raise the possibility of a role for huntingtin in the
      regulation of a ras-related signaling pathway.

PMID- 9285791
TI  - Altered metabolism of familial Alzheimer's disease-linked amyloid precursor
      protein variants in yeast artificial chromosome transgenic mice.
AB  - Missense mutations in the beta-amyloid precursor protein gene (APP) co-segregate
      with a small subset of autosomal dominant familial Alzheimer's disease (FAD)
      cases wherein deposition of the 39-43 amino acid beta-amyloid (A beta) peptide
      and neurodegeneration are principal neuropathological hallmarks. To accurately
      examine the effect of missense mutations on APP metabolism and A beta production
      in vivo, we have introduced yeast artificial chromosomes (YACs) containing the
      entire approximately 400 kbp human APP gene encoding APP harboring either the
      asparagine for lysine and leucine for methionine FAD substitution at codons 670
      and 671 (APP(K670N/M671L)), the isoleucine for valine FAD substitution at codon
      717 (APP(V7171)) or a combination of both substitutions into transgenic mice. We
      demonstrate that, relative to YAC transgenic mice expressing wild-type APP, high
      levels of A beta peptides are detected in the brains of YAC transgenic mice
      expressing human APP(K670N/M671L) that is associated with a concomitant
      diminution in the levels of apha-secretase-generated soluble APP derivatives.
      Moreover, the levels of longer A beta peptides (species terminating at amino
      acids 42/43) are elevated in YAC transgenic mice expressing human APP(V7171).
      These mice should prove valuable for detailed analysis of the in vivo effects of
      the APP FAD mutations in a variety of tissues and throughout aging and for
      testing therapeutic agents that specifically alter APP metabolism and A beta
      production.

PMID- 9285792
TI  - Imprinting of IGF2 and H19: lack of reciprocity in sporadic Beckwith-Wiedemann
      syndrome.
AB  - Genomic imprinting is a novel form of control of gene expression in which the
      transcription of each allele of an imprinted gene is dependent on the sex of the
      gamete from which it was derived; to date > 15 genes have been demonstrated to
      show imprinting. The maintenance of a normal imprinting pattern in many loci has
      been shown to be essential for normal development and adult life. Many tumours,
      and some developmental disorders, exhibit loss of imprinting (LOI) in key genes
      such as insulin-like growth factor 2 (IGF2) which often results in hyperplasia
      and is associated with cancer. The mechanism by which the genomic imprint is
      first established, then maintained, is not understood. However, in the case of
      IGF2, the expression of a neighbouring gene, H19, has been suggested to influence
      its transcription by competition for a common enhancer, thereby generating a
      mutually exclusive and allele-specific pattern of gene expression. Associated
      changes in CpG methylation in discrete areas of both genes have been implicated
      in maintenance of the imprint. We have examined the allele-specific expression of
      IGF2 and H19 in fibroblasts derived from patients with sporadic Beckwith
      Wiedemann syndrome (BWS), a fetal overgrowth syndrome associated with an
      imprinted locus on 11p15.5. We report that the majority of karyotypically normal
      patients show LOI of IGF2 with biallelic expression. In a proportion of these
      patients, loss of IGF2 imprinting was associated with complete suppression of H19
      expression, as predicted by the enhancer competition model. However, in a
      significant number of cases, IGF2 showed biallelic expression even though H19
      expression and methylation status were normal. This indicates that there must be
      an alternative H19-independent pathway by which allele-specific IGF2 expression
      is established or maintained.

PMID- 9285793
TI  - Nuclear localization of SYT, SSX and the synovial sarcoma-associated SYT-SSX
      fusion proteins.
AB  - Synovial sarcoma is characterized by a prevalent chromosomal translocation,
      t(X;18)(p11;q11). As a result of this translocation the SYT gene on chromosome 18
      fuses to either the SSX1 or the SSX2 gene on the X chromosome. In this study, we
      generated polyclonal antibodies against the SYT and SSX2 proteins. These
      antibodies specifically detected both these proteins and the SYT-SSX fusion
      proteins in transfected COS-1 cell extracts. Indirect immunofluorescence analysis
      of COS-1 cells expressing tagged or untagged SYT, SSX2, SYT-SSX1 or SYT-SSX2
      indicated that all these proteins are localized in the nucleus, excluding the
      nucleoli. The SSX2 protein exhibited a diffuse staining pattern whereas both the
      SYT and SYT-SSX proteins appeared in several nuclear dots. Similar nuclear dots
      were also detected in primary synovial sarcoma cells growing in a short-term in
      vitro culture. Double immunofluorescence in conjunction with confocal laser
      scanning microscopy revealed that the SYT and SYT-SSX nuclear dots do not co
      localize with known nuclear structures as e.g. coiled bodies, SC35 interchromatin
      granules or PML bodies. The similar nuclear localization patterns of SYT and SYT
      SSX suggest that the SYT-SSX fusion proteins are directed to SYT-associated
      nuclear domains where an abnormal function may be exerted.

PMID- 9285794
TI  - The SYT protein involved in the t(X;18) synovial sarcoma translocation is a
      transcriptional activator localised in nuclear bodies.
AB  - The t(X;18)(p11.2;q11.2) translocation found in synovial sarcomas results in the
      fusion of the SYT gene on chromosome 18 to either of two closely related genes
      SSX1 and SSX2 on chromosome X. The resulting chimaeric genes express SYT-SSX1 or
      SYT-SSX2 fusion proteins in which the C-terminal amino acids of SYT are replaced
      by amino acids from the C-terminus of the SSX proteins. Using green fluorescent
      protein fusions we demonstrate that the SYT, SSX and the SYT-SSX proteins are
      nuclear proteins. We demonstrate that whilst the SSX1 protein has a uniform
      nuclear distribution the SYT protein has a speckled distribution in the cell
      nucleus, and this distribution is retained with the SYT-SSX2 fusion protein.
      Since the SYT speckles do not co-localise with PML-containing bodies (PODs) or
      spliceosomes it is possible that they represent a novel nuclear structure.
      Transfection of constructs expressing GAL4 fusion proteins demonstrate that the
      SYT domains present in the SYT-SSX fusion proteins can activate transcription of
      a luciferase reporter. It is proposed that the t(X;18) translocation results in
      the generation of an SYT-SSX transcriptional co-activator in which the addition
      of the C-terminal SSX domain to SYT provides a new interacting domain that
      redirects the SYT activation domain to different target promoters.

PMID- 9285795
TI  - Human minisatellite MS32 (D1S8) displays somatic but not germline instability in
      transgenic mice.
AB  - Human minisatellite MS32 (D1S8) shows instability both in the germline and, at
      much lower levels, in somatic DNA. To investigate factors that influence somatic
      and germline mutation, large cosmid-based constructs containing MS32 were
      introduced into mice, bred to homozygosity and tested for instability in blood
      and sperm. Analysis of single copy and multicopy transgenic lines revealed
      somatic mutants occurring at a frequency comparable with that seen in man. As in
      humans, these mutants arose mainly by simple intra-allelic duplications and
      deletions. In contrast, analysis of sperm DNA from four different transgenic
      lines showed no trace of the complex recombination-based germline instability
      seen in man, even using PCR-based approaches capable of detecting very rare
      mutants. These data provide further evidence that germline and somatic mutation
      at human minisatellite MS32 occur via distinct pathways, that a major barrier
      exists to the transfer of germline instability from humans to mice and that the
      mouse germline appears to be protected from mitotic instability of the type seen
      in blood.

PMID- 9285796
TI  - Novel mutations in Sanfilippo A syndrome: implications for enzyme function.
AB  - Sanfilippo syndrome type A or mucopolysaccharidosis IIIA (MPS IIIA) is an
      autosomal recessive lysosomal storage disorder caused by the deficiency of
      sulfamidase. The resulting lysosomal storage of heparan sulfate may lead to
      severe neurodegeneration preceded by progressive dementia, often combined with
      aggressive and hyperactive behaviour. A total of 109 patients from four different
      geographic areas were screened for the common mutation R245H and two other
      previously identified mutations. SSCP analysis of exons was used to characterize
      the unknown alleles. We identified 16 novel sequence variants, 12 of them likely
      to be pathogenic. The majority of the pathogenic variants were single base pair
      changes leading to missense mutations. Several single base pair
      deletions/insertions and one nonsense mutation were also identified. Altogether,
      we were able to characterize 55% of the pathogenic alleles. Sequence homology
      between sulfamidase and N-acetylgalactosamine 4-sulfatase, the first sulfatase to
      have its tertiary structure defined, suggests that amino acid residues R74 and
      T79, which were found to be mutated, are likely to be involved in the formation
      of the active site of sulfamidase. R245H accounts for 31% of the Sanfilippo A
      alleles in Australasia, for 19.2% of the alleles in patients from the UK and has
      a high frequency of 57.8% in patients from The Netherlands. The identification of
      mutations common in certain geographic regions or ethnic groups will help in the
      diagnosis of MPS IIIA and allow carrier testing and improved genetic counselling.

PMID- 9285797
TI  - Anhidrotic ectodermal dysplasia (EDA) protein expressed in MCF-7 cells associates
      with cell membrane and induces rounding.
AB  - Anhidrotic ectodermal dysplasia (EDA) is a rare X-linked recessive disorder
      characterized by the absence or hypoplasia of hair, teeth and sweat glands. The
      gene responsible for the disorder has recently been cloned. The predicted gene
      product is a 135 amino acid protein with no significant homology to previously
      known proteins. As a first step to analyze function, we have studied the
      subcellular localization of the EDA gene product expressed in two epithelial cell
      lines, COS-1 and MCF-7. Biochemical fractionation and confocal imaging analysis
      show that, in agreement with a single putative transmembrane domain inferred from
      its sequence, the EDA protein is transported to the plasma membrane. Moreover, in
      MCF-7 cells expression of EDA is associated with rounding and detachment of the
      cells. These results suggest that the EDA protein may be involved in cellular
      dynamics or signaling.

PMID- 9285798
TI  - Cloning of Tabby, the murine homolog of the human EDA gene: evidence for a
      membrane-associated protein with a short collagenous domain.
AB  - X-Linked hypohidrotic ectodermal dysplasia (XLHED) is a human congenital disorder
      resulting in abnormal tooth, hair and sweat gland development. A candidate gene
      for the disorder has been cloned, but the function and full size of its putative
      protein product is unclear. We have identified a candidate cDNA for the mouse
      Tabby gene (Ta), which, based on phenotype and syntenic mapping, is postulated to
      represent the analogous murine disorder. Mutations have been identified in three
      different Ta alleles and Northern analysis indicates that the gene is expressed
      at increasing levels during embryogenesis (11-17 days p.c.), the period when
      affected structures develop. The putative protein product encoded by exon 1 is
      highly homologous (87% identical) to the predicted EDA protein product (135 amino
      acids), including the presence of a single transmembrane domain. However, the
      murine cDNA also encodes an additional 246 amino acids, which contains a short
      collagenous domain (Gly-X-Y)19. This predicted structure is similar to a number
      of membrane-associated proteins with either single or multiple collagenous
      domains in their extracellular C-terminal regions. Since mutations can only be
      identified in 10-15% of families with XLHED, it is likely that additional
      homologous exons exist for the human EDA gene. Hybridization of YACs from the EDA
      region with the Ta cDNA support this hypothesis. The predicted extracellular
      collagenous domain of this membrane protein may play a key role in epithelial
      mesenchymal interactions, defects of which are thought to underlie the Ta/XLHED
      phenotype.

PMID- 9285799
TI  - The human COX10 gene is disrupted during homologous recombination between the 24
      kb proximal and distal CMT1A-REPs.
AB  - The CMT1A-REPs are two large directly repeating DNA sequences located on
      chromosome 17p11.2-p12 flanking the region duplicated in patients with Charcot
      Marie-Tooth disease type 1A (CMT1A) and deleted in patients with hereditary
      neuropathy with liability to pressure palsies (HNPP). We have sequenced two
      cosmids, c74F4 and c15H12, which contain the entire proximal and distal CMT1A
      REPs and determined that these repeats are approximately 99% identical across a
      24,011 bp region. In addition, both contain an exon of the human heme
      A:farnesyltransferase gene (COX10). Hybridization studies revealed that COX10
      spans the distal CMT1A-REP, while the proximal CMT1A-REP contains an isolated
      COX10 'pseudo-exon'. There is also a COX10 hybridization signal on chromosome 10
      which appears to represent a processed pseudogene. We propose that the distal
      CMT1A-REP represents the progenitor copy of COX10 exon VI which was duplicated
      with surrounding intronic sequences during mammalian genome evolution and that
      the HNPP deletion results in a COX10 null allele.

PMID- 9285800
TI  - Connexin26 mutations associated with the most common form of non-syndromic
      neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans.
AB  - Non-syndromic neurosensory autosomal recessive deafness (NSRD) is the most common
      form of genetic hearing loss. Previous studies defined at least 15 human NSRD
      loci. Recently we demonstrated that DFNB1, located on the long arm of chromosome
      13, accounts for approximately 80% of cases in the Mediterranean area. Further
      analysis with additional markers now identifies several recombinants which narrow
      the candidate region to approximately 5 cM, encompassed by markers D13S141 and
      D13S232 and including several ESTs and candidate genes, including the connexin26
      (GJB2) gene. Analysis of PCR products from our affected patients' DNA shows two
      frameshift mutations in the connexin26 gene. Deletion of a G within a stretch of
      six Gs at position 35 of the GJB2 cDNA (mutation 35delG) leads to premature chain
      termination and is present in 63% of NSRD chromosomes, demonstrating linkage to
      chromosome 13. Deletion of a T at position 167 of GJB2 (mutation 167delT), also
      resulting in premature chain termination, was detected in another patient. Four
      neutral sequence polymorphisms were also identified. These findings are in
      agreement with a recent study showing that mutations in the connexin26 gene are
      associated with genetic forms of deafness in three Pakistani families and that
      GJB2 is DFNB1. Connexin26 is a member of a large family of proteins involved in
      formation of gap junctions, which are involved in electrical synapses and the
      direct transfer of small molecules and ionic currents between neighboring cells.
      The identification of GJB2 as the DFNB1 gene should provide a better
      understanding of the biology of normal and abnormal hearing, help form the basis
      for diagnosis and may facilitate development of strategies for treatment of this
      common genetic disorder.

PMID- 9285801
TI  - Proton MR spectroscopic imaging of the striatum in Parkinson's disease.
AB  - Assess the feasibility of proton MR spectroscopic imaging (1H-MRSI) of the
      striatum (putamen and caudate nucleus) in patients with Parkinson's disease and
      evaluate striatal neuronal density. Proton MRSI of the striatum and thalamus with
      2 cc spatial resolution was performed in 10 patients with Parkinson's disease, 1
      patient with atypical parkinsonism, and 13 control subjects. Single voxel proton
      MR spectra with signals from choline metabolites (Cho), creatine metabolites
      (Cr), and the putative neuronal marker, N-acetyl-aspartate (NAA), were obtained
      from the putamen and thalamus, but not the caudate nucleus, of patients with
      parkinsonism and control subjects. Metabolite rations in controls and patients
      were: in putamen NAA/Cho 1.70 +/- 0.25 vrs 1.74 +/- 0.32, NAA/Cr 2.80 +/- 0.79
      vrs 2.36 +/- 0.42, Cho/Cr 1.63 +/- 0.25 vrs 1.39 +/- 0.3; in thalamus, NAA/Cho
      1.78 +/- 0.15 vrs 1.62 +/- 0.22, NAA/Cr 2.78 +/- 0.34 vrs 2.64 +/- 0.41, Cho/Cr
      1.57 +/- 0.25 vrs 1.65 +/- 0.28. There were no statistically significant
      differences between patients and controls. The putaminal NAA/Cho ratio of the
      single subject with atypical parkinsonism was lower than that of 9 of the 10
      patients with classic Parkinson's disease and 11 of the 13 control subjects.
      Likewise, the putaminal NAA/Cr ratio in the single subject with atypical
      parkinsonism was lower than that of 7of the patients with guided selection of
      spectra from very small brain volumes, is a technique that can be used to
      evaluate neuronal density in individual subcortical gray nuclei in the brains of
      patients with parkinsonism. Using this technique, we have shown that Parkinson's
      disease produces no change in relative levels of the neuronal marker, NAA, in the
      putamen.

PMID- 9285802
TI  - Focal hepatic lymphoma: magnetic resonance demonstration using current techniques
      including gadolinium enhancement.
AB  - This study demonstrates the appearance of focal hepatic lymphoma using current
      magnetic resonance techniques including gadolinium enhancement. Fifteen patients
      with hepatic lymphoma were imaged at 1.5T. T1-weighted, T2-weighted, immediate,
      and 5-10-min delayed T1-weighted spoiled gradient echo images were acquired in
      all patients. Determination was made of lesion size, number, morphology, and
      signal intensity of lesions on all sequences. Seven patients had solitary lesions
      and 8 patients had multiple lesions. Focal lesions of hepatic lymphoma ranged in
      size from 5 mm to 15 cm. They were well defined masses with mild to moderate low
      signal intensity relative to liver on T1-weighted images. Lymphoma lesions in 6
      patients were moderately high in signal intensity on T2-weighted images compared
      with liver (Type I lesions), and enhancement of lesions was intense on early post
      gadolinium images in 5 of these patients. Lymphoma lesions in 6 patients were
      mildly hypointense to mildly hyperintense on T2-weighted images compared to liver
      (Type II lesions), and lesions in 5 of these patients enhanced minimally on the
      early post-gadolinium spoiled gradient echo images. The remaining 3 patients had
      received chemotherapy before the magnetic resonance examination, and the imaging
      findings varied reflecting presumed differences in treatment responses. Transient
      ill defined perilesional enhancement on immediate post-gadolinium spoiled
      gradient echo images was observed in 9 patients including patients with either
      type of lesion. Focal lesions of hepatic lymphoma are usually low in signal
      intensity on T1-weighted images but have variable signal intensity on T2-weighted
      images. In general, lesions that are mildly hypointense to minimally hyperintense
      in signal intensity on T2-weighted images enhance minimally, and lesions
      moderately high in signal intensity of T2-weighted images enhance intensely.
      Transient increased perilesional enhancement is common.

PMID- 9285804
TI  - Fast gradient echo MR imaging of the liver enhanced with superparamagnetic iron
      oxide.
AB  - The purpose of this study was to develop a breath-hold technique for hepatic
      imaging using SPIO-enhanced gradient echo. Pre- and post-SPIO driven equilibrium
      fast gradient echo scans were performed on five healthy subjects. Scan parameters
      were established to emphasize large pre-/post-signal differences while
      maintaining a scan time conducive to breath-hold. Hepatic post-SPIO signal
      reduction was at least fifty percent with diagnostic image quality in all
      subjects. SPIO-enhanced gradient echo provides slightly less hepatic signal
      reduction to spin echo techniques but can be performed within a single breath
      hold. This technique may be advantageous over SE in assessing hepatic pathology
      in subjects unable to lay motionless for prolonged intervals, such as children.

PMID- 9285803
TI  - Magnetic resonance renography: optimisation of pulse sequence parameters and Gd
      DTPA dose, and comparison with radionuclide renography.
AB  - The aim of this study was to assess the feasibility of magnetic resonance
      renography (MRR) using gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) in
      comparison with conventional radionuclide renography (RR) using technetium-99m
      DTPA (99mTc-DTPA). MRR has many advantages over RR, including lack of ionising
      radiation, increased spatial resolution, and visible background anatomy. By
      optimising the pulse sequence, we developed an MRR protocol in which signal
      intensity is linear with Gd-DTPA concentration over a clinically relevant range.
      Twenty-nine patients and a volunteer were studied using this protocol. Magnetic
      resonance renography was performed using three different doses of Gd-DTPA: 0.1
      mmol kg-1 (n = 13), 0.05 mmol kg-1 (n = 7), and 0.025 mmol kg-1 (n = 9). Each
      patient was also assessed using radionuclide renography. The resulting renograms
      were assessed in terms of time to peak signal intensity, signal decrease after
      peak, and kidney function ratios calculated from both the areas underneath and
      the slopes of the uptake curves. We have shown that the MR renograms obtained
      using low dose Gd-DTPA correlate best with the radionuclide renograms. Remaining
      discrepancies may be explained by variations in the injection procedures (hence
      in arterial input functions) and the limited coverage of the three MRR slices
      compared to the whole body projection of RR. Furthermore, at high local
      concentrations, signal becomes independent of T1 and is dominated by T2.

PMID- 9285805
TI  - Temperature determination in the frozen region during cryosurgery of rabbit liver
      using MR image analysis.
AB  - Cryosurgery currently is being used clinically to treat tumors in internal organs
      such as the liver and prostate. Although performed at present under ultrasound
      monitoring, magnetic resonance imaging (MRI)-guidance of these procedures not
      only permits monitoring of the frozen region during cryosurgery but also makes it
      possible to determine the temperature distribution in the frozen region, which is
      not possible using ultrasound monitoring. A good estimate of the region of
      destruction in the tissue can be obtained from correlating the temperature
      distribution and the time course of the freezing with the image of the frozen
      region. Unfortunately, MR pulse sequence-based temperature determination
      techniques such as diffusion, relaxation time, and chemical shift cannot be used
      for measuring the temperature in the frozen region because the T2 of the frozen
      regions is so short that there is effectively no RF signal from the frozen
      region. This paper describes a numerical technique for determining the two
      dimensional temperature distribution in the frozen region during MR image-guided
      cryosurgery of normal liver in rabbits. The technique involves solving the energy
      equation numerically in the frozen region to determine the temperature
      distribution there. The boundary conditions needed to solve the equation are
      determined from MR images of the frozen tissue during cryosurgery and from the
      measured temperature of the cryoprobe. The calculated temperature in the frozen
      region is then correlated with the damaged region (cryolesion) determined from
      post mortem histologic evaluation.

PMID- 9285806
TI  - Using prior knowledge of human anatomy to constrain MR image acquisition and
      reconstruction: half k-space and full k-space techniques.
AB  - In this note, we demonstrate how to utilize prior knowledge of human cranial
      anatomy to constrain full k-space and half k-space acquisition and reconstruction
      of 128 times 128 images. We used a database of magnetic resonance head images to
      derive new basis functions which represent the most important features of the
      head. the "training" images were also used to derive formulas for reconstructing
      head images from a subset of the usual 128 phase-encoded signals and to determine
      the optimal k-space locations of those signal measurements. We used this
      algorithm, called Feature-Recognizing MRI, to reconstruct 128 times 128 head
      images from 50-60% of the signals filling the full k-space. Furthermore, we
      combined the algorithm with a conventional half k-space technique to create 128
      times 128 images from only 60% of the 80 signals required by the usual
      unconstrained half k-space imaging. Thus, the prior knowledge represented by the
      image database, together with a half k-space technique, made it possible to
      construct accurate magnetic resonance images from only 30-40% of the complete set
      of 128 signals. In other words, a database of head images was used to devise a
      1/3 k-space method for imaging the head.

PMID- 9285808
TI  - Copper concentration in hyperintense hepatocellular carcinomas of Long-Evans
      cinnamon rats on T1-weighted images.
AB  - The Long-Evans Cinnamon (LEC) rat has abnormal intrahepatic copper accumulation
      and spontaneously develops hepatocellular carcinomas following hereditary
      hepatitis. The hepatocellular carcinomas are very similar to human well
      differentiated hepatocellular carcinoma in histopathological features and on MR
      images. Copper is believed to be one of the causes of hyperintensity of
      hepatocellular carcinomas compared to surrounding non-cancerous tissues on T1
      weighted MR image. Eight LEC rats were studied by MR imaging. We measured copper
      concentrations from the hepatocellular carcinomas and surrounding non-cancerous
      liver tissues. Signal intensity of hepatocellular carcinomas without cystic areas
      was iso- to slightly hyperintense relative to surrounding non-cancerous tissues
      on T1-weighted images. Histopathologically, most of the tumors resembled human
      highly or well-differentiated hepatocellular carcinomas. Copper concentrations of
      the hepatocellular carcinomas were lower than the surrounding non-cancerous liver
      tissues. Copper may not be the cause of increased signal intensity typically
      observed on T1-weighted images of hepatocellular carcinomas.

PMID- 9285807
TI  - Watershed-based segmentation of 3D MR data for volume quantization.
AB  - The aim of this work is the development of a semiautomatic segmentation technique
      for efficient and accurate volume quantization of Magnetic Resonance (MR) data.
      The proposed technique uses a 3D variant of Vincent and Soilles immersion-based
      watershed algorithm that is applied to the gradient magnitude of the MR data and
      that produces small volume primitives. The known drawback of the watershed
      algorithm, oversegmentation, is strongly reduced by a priori application of a 3D
      adaptive anisotropic diffusion filter to the MR data. Furthermore,
      oversegmentation is a posteriori reduced by properly merging small volume
      primitives that have similar gray level distributions. The outcome of the
      proceeding image processing steps is presented to the user for manual
      segmentation. Through selection of volume primitives, the user quickly segments
      of first slice, which contains the object of interest. Afterwards, the subsequent
      slices are automatically segmented by extrapolation. Segmentation results are
      contingently manually corrected. The proposed segmentation technique is tested on
      phantom objects, where segmentation errors less than 2% are observed. In
      addition, the technique is demonstrated on 3D MR data of the mouse head from
      which the cerebellum is extracted. Volumes of the mouse cerebellum and the mouse
      brains in toto are calculated.

PMID- 9285809
TI  - Application of NMR microscopy to the morphological study of the silkworm, Bombyx
      mori, during its metamorphosis.
AB  - Zero (ZQ) and double (DQ) quantum 2D chemical shift selective and spin-echo 3D
      NMR imaging at microscopy resolution, has been applied to the morphological study
      of silkworm, Bombyx mori, during its metamorphosis. Attention had been focused on
      the evolution of the internal structure of the insect during its postembryonal
      life occurring through the larval, pupal and adult development. A major objective
      of this work was the characterization of the silk glands, responsible for the
      synthesis and secretion of fibroin and sericin, through the changes of
      distribution and mobility of water, by imaging the water protons during
      postembryonal life stages. Moreover, alanine deriving from silk gland proteins
      was imaged during the last life stage of Bombyx mori.

PMID- 9285810
TI  - A CT using longitudinally detected ESR (LODESR-CT) of intraperitoneally injected
      nitroxide radical in a rat's head.
AB  - We have developed an in vivo longitudinally detected ESR (LODESR) imaging system
      operating at 700 MHz based on a loop-gap resonator and a pair of saddle-type
      pickup coils. A good linear relationship between the LODESR signal intensity and
      the applied power in a range up to 15.8 W was obtained. The detection of LODESR
      signals was barely affected by variations in the resonant properties. The
      characteristic of LODESR is suitable for in vivo examination. Using this system,
      we succeeded in obtaining LODESR-CT images of the head region of a rat after the
      intraperitoneal injection of a nitroxide radical.

PMID- 9285811
TI  - Proton resonance imaging and relaxation in raw and cooked hen eggs.
AB  - In-vivo proton magnetic resonance imaging and relaxation time measurements were
      carried out on raw and cooked eggs. The relaxation time measurements revealed
      several interesting results. While there was very little change in the T1 values
      between the raw and cooked egg white, the T2 values followed the decreasing trend
      expected of water becoming bound. However, both the CH2 and CH3 moieties of the
      yolk lipids registered a statistically significant increase in their relaxation
      times. The T2 of the CH2 group, in particular, increased by 113% in the cooked
      egg. No striking changes, however, were observed between the proton images of the
      raw and cooked eggs.

PMID- 9285812
TI  - Three dimensional imaging of the Belousov-Zhabotinsky reaction using magnetic
      resonance.
AB  - The combination of 3D magnetic resonance imaging data with polygon based computer
      graphic display software is ideally suited to the study of the Belousov
      Zhabotinsky reaction in extended volumes. In this paper we present the first true
      three dimensional visualization of experimental data from the Belousov
      Zhabotinsky reaction. The time evolution of a twisted scroll wave like
      isoconcentration surface and its organizing filament are demonstrated for the
      manganese-catalyzed B-Z mixture. These techniques extend the experimental study
      of the B-Z reaction as a class of pattern-forming systems to the third dimension.
      The limitations of the technique are discussed.

PMID- 9285813
TI  - Alpha-adaptin, a marker for endocytosis, is expressed in complex patterns during
      Drosophila development.
AB  - A Drosophila cDNA encoding a structural homologue of the mammalian coated vesicle
      component alpha-adaptin (AP2 adaptor complex) has been cloned and sequenced. The
      mammalian and invertebrate sequences are highly conserved, especially within the
      amino terminal region, a domain that mediates interactions with other components
      within the AP2 complex and with specific receptors tails. Mammalian alpha
      adaptins are encoded by two genes; however, Drosophila alpha-adaptin has a single
      gene locus, within polytene bands 21C2-C3 on the left arm of the chromosome 2,
      closely adjacent to the paired homeobox gene aristaless. There seem to be at
      least two Drosophila alpha-adaptin transcripts expressed, plausibly by
      alternative splicing. One of the transcripts is more abundant during early
      embryogenesis and may be of maternal origin. We have studied the distribution of
      the alpha-adaptin protein throughout embryogenesis and at the neuromuscular
      junction of the third instar larva. During cellularization of the blastoderm
      embryo, the protein is seen between and ahead of the elongating nuclei, and then
      redistributes to the cell surface during gastrulation. These observations suggest
      a role for endocytosis in cellularization and are consistent with the finding
      that dynamin (the shibire gene product), another component of the endocytic
      mechanism, is required for cellularization. At later stages of embryogenesis,
      alpha-adaptin is expressed in complex and dynamic patterns. It is strongly
      induced in elements of the central and peripheral nervous system (e.g., in
      neuroblasts, the presumptive stomatogastric nervous system, and the lateral
      chordotonal sense organs), in the Garland cells, the adult midgut precursors, the
      antenno-maxillary complex, the endoderm, the fat bodies, and the visceral
      mesoderm. In the larva, alpha-adaptin is localized at the plasma membrane in the
      synaptic boutons of the neuromuscular junctions. The cells expressing high levels
      of alpha-adaptin are known or expected to support high levels of endocytosis;
      thus, this coated vesicle protein seems to be an excellent marker for endocytic
      activity. The expression patterns of dynamin, detected in the embryo by in situ
      hybridization methods, are very similar to those reported here for alpha-adaptin
      reflecting the likely coordinated expression of endocytic components. Taken
      together with previous evidence, our results suggest that endosomal vesicle
      trafficking, membrane recycling, and the regulation of endocytosis play critical
      roles in the wide range of developmental processes.

PMID- 9285814
TI  - Protein-protein interactions in the synaptonemal complex.
AB  - In mammalian systems, an approximately M(r) 30,000 Cor1 protein has been
      identified as a major component of the meiotic prophase chromosome cores, and a
      M(r) 125,000 Syn1 protein is present between homologue cores where they are
      synapsed and form the synaptonemal complex (SC). Immunolocalization of these
      proteins during meiosis suggests possible homo- and heterotypic interactions
      between the two as well as possible interactions with yet unrecognized proteins.
      We used the two-hybrid system in the yeast Saccharomyces cerevisiae to detect
      possible protein-protein associations. Segments of hamsters Cor1 and Syn1
      proteins were tested in various combinations for homo- and heterotypic
      interactions. In the cause of Cor1, homotypic interactions involve regions
      capable of coiled-coil formation, observation confirmed by in vitro affinity
      coprecipitation experiments. The two-hybrid assay detects no interaction of Cor1
      protein with central and C-terminal fragments of Syn1 protein and no homotypic
      interactions involving these fragments of Syn1. Hamster Cor1 and Syn1 proteins
      both associate with the human ubiquitin-conjugation enzyme Hsubc9 as well as with
      the hamster Ubc9 homologue. The interactions between SC proteins and the Ubc9
      protein may be significant for SC disassembly, which coincides with the repulsion
      of homologs by late prophase I, and also for the termination of sister centromere
      cohesiveness at anaphase II.

PMID- 9285815
TI  - Lysophosphatidic acid and microtubule-destabilizing agents stimulate fibronectin
      matrix assembly through Rho-dependent actin stress fiber formation and cell
      contraction.
AB  - Fibronectin (FN) matrix assembly is a cell-dependent process mediated by cell
      surface-binding sites for the 70-kDa amino-terminal region of FN. We have shown
      recently that lysophosphatidic acid (LPA) is a stimulator of FN matrix assembly.
      Disruption of microtubules has been shown to mimic some of the intracellular
      effects of LPA including the formation of actin stress fibers and myosin light
      chain phosphorylation. We compared the effects of microtubule disruption and LPA
      on FN binding and actin cytoskeleton organization. The disruption of microtubules
      by nocodazole or vinblastine increased FN binding to adherent cells. The
      modulation of binding sites was rapid, dynamic, and reversible. Enhanced binding
      was due to increases in both the number and affinity of binding sites. These
      effects are similar to the effects of LPA on FN binding. Binding induced by
      nocodazole was inhibited by the microtubule-stabilizing agent Taxol but not by
      pretreatment with a concentration of phospholipase B that totally abolished the
      stimulatory effect of LPA. Fluorescence microscopy revealed a close correlation
      among actin stress fiber formation, cell contraction, and FN binding. Blockage of
      the small GTP binding protein Rho or actin-myosin interactions inhibited the
      effects of both nocodazole and LPA on FN binding. These observations demonstrate
      that Rho-dependent actin stress fiber formation and cell contraction induce
      increased FN binding and represent a rapid labile way that cells can modulate FN
      matrix assembly.

PMID- 9285817
TI  - Nuclear membrane vesicle targeting to chromatin in a Drosophila embryo cell-free
      system.
AB  - A Drosophila cell-free system was used to characterize proteins that are required
      for targeting vesicles to chromatin and for fusion of vesicles to form nuclear
      envelopes. Treatment of vesicles with 1 M NaCl abolished their ability to bind to
      chromatin. Binding of salt-treated vesicles to chromatin could be restored by
      adding the dialyzed salt extract. Lamin Dm is one of the peripheral proteins
      whose activity was required, since supplying interphase lamin isoforms Dm1, and
      Dm2 to the assembly extract restored binding. As opposed to the findings in
      Xenopus, okadaic acid had no effect on vesicle binding. Trypsin digestion of the
      salt-stripped vesicles eliminated their association with chromatin even in the
      presence of the dialyzed salt extract. One vesicles attached to chromatin
      surface, fusion events took place were found to be sensitive to guanosine 5'
      [gamma-thio]triphosphate (GTP gamma S). These chromatin-attached vesicles
      contained lamin Dm and otefin but not gp210. Thus, these results show that in
      Drosophila there are two populations of nuclear vesicles. The population that
      interacts first with chromatin contains lamin and otefin and requires both
      peripheral and integral membrane proteins, whereas fusion of vesicles requires
      GTPase activity.

PMID- 9285816
TI  - SIC1 is ubiquitinated in vitro by a pathway that requires CDC4, CDC34, and
      cyclin/CDK activities.
AB  - Traversal from G1 to S-phase in cycling cells of budding yeast is dependent on
      the destruction of the S-phase cyclin/CDK inhibitor SIC1. Genetic data suggest
      that SIC1 proteolysis is mediated by the ubiquitin pathway and requires the
      action of CDC34, CDC4, CDC53, SKP1, and CLN/CDC28. As a first step in defining
      the functions of the corresponding gene products, we have reconstituted SIC1
      multiubiquitination in DEAE-fractionated yeast extract. Multiubiquitination
      depends on cyclin/CDC28 protein kinase and the CDC34 ubiquitin-conjugating
      enzyme. Ubiquitin chain formation is abrogated in cdc4ts mutant extracts and
      assembly restored by the addition of exogenous CDC4, suggesting a direct role for
      this protein in SIC1 multiubiquitination. Deletion analysis of SIC1 indicates
      that the N-terminal 160 residues are both necessary and sufficient to serve as
      substrate for CDC34-dependent ubiquitination. The complementary C-terminal
      segment of SIC1 binds to the S-phase cyclin CLB5, indicating a modular structure
      for SIC1.

PMID- 9285818
TI  - Membrane translocation of mitochondrially coded Cox2p: distinct requirements for
      export of N and C termini and dependence on the conserved protein Oxa1p.
AB  - To study in vivo the export of mitochondrially synthesized protein from the
      matrix to the intermembrane space, we have fused a synthetic mitochondrial gene,
      ARG8m, to the Saccharomyces cerevisiae COX2 gene in mitochondrial DNA. The Arg8mp
      moiety was translocated through the inner membrane when fused to the Cox2p C
      terminus by a mechanism dependent on topogenic information at least partially
      contained within the exported Cox2p C-terminal tail. The pre-Cox2p leader peptide
      did not signal translocation. Export of the Cox2p C-terminal tail, but not the N
      terminal tail, was dependent on the inner membrane potential. The mitochondrial
      export system does not closely resemble the bacterial Sec translocase. However,
      normal translocation of both exported domains of Cox2p was defective in cells
      lacking the widely conserved inner membrane protein Oxa1p.

PMID- 9285819
TI  - The spindle pole body of Schizosaccharomyces pombe enters and leaves the nuclear
      envelope as the cell cycle proceeds.
AB  - The cycle of spindle pole body (SPB) duplication, differentiation, and
      segregation in Schizosaccharomyces pombe is different from that in some other
      yeasts. Like the centrosome of vertebrate cells, the SPB of S. pombe spends most
      of interphase in the cytoplasm, immediately next to the nuclear envelope. Some
      gamma-tubulin is localized on the SPB, suggesting that it plays a role in the
      organization of interphase microtubules (MTs), and serial sections demonstrate
      that some interphase MTs end on or very near to the SPB. gamma-Tubulin is also
      found on osmiophilic material that lies near the inner surface of the nuclear
      envelope, immediately adjacent to the SPB, even though there are no MTs in the
      interphase nucleus. Apparently, the MT initiation activities of gamma-tubulin in
      S. pombe are regulated. The SPB duplicates in the cytoplasm during late G2 phase,
      and the two resulting structures are connected by a darkly staining bridge until
      the mitotic spindle forms. As the cell enters mitosis, the nuclear envelope
      invaginates beside the SPB, forming a pocket of cytoplasm that accumulates dark
      amorphous material. The nuclear envelope then opens to form a fenestra, and the
      duplicated SPB settles into it. Each part of the SPB initiates intranuclear MTs,
      and then the two structures separate to lie in distinct fenestrae as a bipolar
      spindle forms. Through metaphase, the SPBs remain in their fenestrae, bound to
      the polar ends of spindle MTs; at about this time, a small bundle of cytoplasmic
      MTs forms in association with each SPB. These MTs are situated with one end near
      to, but not on, the SPBs, and they project into the cytoplasm at an orientation
      that is oblique to the simple axis. As anaphase proceeds, the nuclear fenestrae
      close, and the SPBs are extruded back into the cytoplasm. These observations
      define new fields of enquiry about the control of SPB duplication and the
      dynamics of the nuclear envelope.

PMID- 9285820
TI  - Yeast actin cytoskeleton mutants accumulate a new class of Golgi-derived
      secretary vesicle.
AB  - Many yeast actin cytoskeleton mutants accumulate large secretory vesicles and
      exhibit phenotypes consistent with defects in polarized growth. This, together
      with actin's polarized organization, has suggested a role for the actin
      cytoskeleton in the vectorial transport of late secretory vesicles to the plasma
      membrane. By using ultrastructural and biochemical analysis, we have
      characterized defects manifested by mutations in the SLA2 gene (also known as the
      END4 gene), previously found to affect both the organization of the actin
      cytoskeleton and endocytosis in yeast. Defects in cell wall morphology,
      accumulated vesicles, and protein secretion kinetics were found in sla2 mutants
      similar to defects found in act1 mutants. Vesicles that accumulate in the sla2
      and act1 mutants are immunoreactive with antibodies directed against the small
      GTPase Ypt1p but not with antibodies directed against the homologous Sec4p found
      on classical "late" secretory vesicles. In contrast, the late-acting secretory
      mutants sec1-1 and sec6-4 are shown to accumulate anti-Sec4p-positive secretory
      vesicles as well as vesicles that are immunoreactive with antibodies directed
      against Ypt1p. The late sec mutant sec4-8 is also shown to accumulate Ypt1p
      containing vesicles and to exhibit defects in actin cytoskeleton organization.
      These results indicate the existence of at least two classes of morphologically
      similar, late secretory vesicles (associated with Ypt1p+ and Sec4p+,
      respectively), one of which appears to accumulate when the actin cytoskeleton is
      disorganized.

PMID- 9285821
TI  - High-resolution calcium mapping of the endoplasmic reticulum-Golgi-exocytic
      membrane system. Electron energy loss imaging analysis of quick frozen-freeze
      dried PC12 cells.
AB  - The calcium pools segregated within the endoplasmic reticulum, Golgi complex,
      exocytic, and other organelles are believed to participate in the regulation of a
      variety of cell functions. Until now, however, the precise intracellular
      distribution of the element had not been established. Here, we report about the
      first high-resolution calcium mapping obtained in neurosecretory PC12 cells by
      the imaging mode of the electron energy loss spectroscopy technique. The
      preparation procedure used included quick freezing of cell monolayers, followed
      by freeze-drying, fixation with OSO4 vapors, resin embedding, and cutting of very
      thin sections. Conventional electron microscopy and high-resolution
      immunocytochemistry revealed a high degree of structural preservation, a
      condition in which inorganic elements are expected to maintain their native
      distribution. Within these cells, calcium signals of nucleus, cytosol, and most
      mitochondria remained below detection, whereas in other organelles specific
      patterns were identified. In the endoplasmic reticulum, the distribution was
      heterogeneous with strongly positive cisternae (more often the nuclear envelope
      and stacks of parallel elements that are frequent in quick frozen preparations)
      lying in the proximity of or even in direct continuity with other, apparently
      negative cisternae. The Golgi complexes were labeled strongly and uniformly in
      all cisternae and part of their vesicles, with no appreciable differences along
      the cis-trans axis. Weaker or negative signals were recorded from the trans-Golgi
      network elements and from scattered vesicles, whereas in contrast secretion
      granules were strongly positive for calcium. These results are discussed in
      relation to the existing knowledge about the mechanisms of calcium transport in
      the variations organelles, and about the processes and functions regulated by
      organelle lumenal calcium in eukaryotic cells.

PMID- 9285822
TI  - Tissue inhibitor of metalloproteinases-2 is expressed in the interstitial matrix
      in adult mouse organs and during embryonic development.
AB  - Tissue inhibitor of metalloproteinases-2 (TIMP-2) is a member of a family of
      inhibitors of matrix-degrading metalloproteinases. A better insight into the role
      of this inhibitor during development and in organ function was obtained by
      examining the temporospatial expression of TIMP-2 in mice. Northern blot analysis
      indicated high levels of TIMP-2 mRNA in the lung, skin, reproductive organs, and
      brain. Lower levels of expression were found in all other organs with the
      exception of the liver and gastrointestinal tissue, which were negative of these
      tissues with complete absence of TIMP-2 mRNA in the epithelium. In the testis,
      TIMP-2 was present in the Leydig cells, and in the brain, it was expressed in pia
      matter and in neuronal tissues. TIMP-2 expression in the placenta increased
      during late gestation and was particularly abundant in spongiotrophoblasts In
      mouse embryo (day 10.5-18.5), TIMP-2 mRNA was abundant in mesenchymal tissues
      that surrounded developing epithelia and maturing skeleton. The pattern of
      expression significantly differs from that observed with TIMP-1 and TIMP-3,
      therefore, suggesting specific roles for each inhibitor during tissue remodeling
      and development.

PMID- 9285823
TI  - A sorting nexin-1 homologue, Vps5p, forms a complex with Vps17p and is required
      for recycling the vacuolar protein-sorting receptor.
AB  - A number of the Saccharomyces cerevisiae vacuolar protein-sorting (vps) mutants
      exhibit an altered vacuolar morphology. Unlike wild-type cells that contain 1-3
      large vacuolar structures, the class B vps5 and vps17 mutant cells contain 10-20
      smaller vacuole-like compartments. To explore the role of these VPS gene products
      in vacuole biogenesis, we cloned and sequenced VPS5 and characterized its protein
      products. The VPS5 gene is predicted to encode a very hydrophilic protein of 675
      amino acids that shows significant sequence homology with mammalian sorting nexin
      1. Polyclonal antiserum directed against the VPS5 gene product detects a single,
      cytoplasmic protein that is phosphorylated specifically on a serine residue(s).
      Subcellular fractionation studies indicate that Vps5p is associated peripherally
      with a dense membrane fraction distinct from Golgi, endosomal, and vacuolar
      membranes. This association was found to be dependent on the presence of another
      class B VPS gene product, Vps17p. Biochemical cross-linking studies demonstrated
      that Vps5p and Vps17p physically interact. Gene disruption experiments show that
      the VPS5 genes product is not essential for cell viability; however, cells
      carrying the null allele contain fragmented vacuoles and exhibit defects in
      vacuolar protein-sorting similar to vps17 null mutants. More than 95% of
      carboxypeptidase Y is secreted from these cells in its Golgi-modified p2
      precursor form. Additionally, the Vps10p vacuolar protein-sorting receptor is
      mislocalized to the vacuole in vps5 mutant cells. On the basis of these and other
      observations, we propose that the Vps17p protein complex may participate in the
      intracellular trafficking of the Vps10p-sorting receptor, as well as other later
      Golgi proteins.

PMID- 9285825
TI  - Complexes between nascent polypeptides and their molecular chaperones in the
      cytosol of mammalian cells.
AB  - Folding of newly synthesized proteins in vivo is believed to be facilitated by
      the cooperative interaction of a defined group of proteins known as molecular
      chaperones. We investigated the direct interaction of chaperones with nascent
      polypeptides in the cytosol of mammalian cells by multiple methods. A new
      approach using a polyclonal antibody to puromycin allowed us to tag and capture a
      population of truncated nascent polypeptides with no bias as to the identity of
      the bound chaperones. In addition, antibodies that recognize the cytosolic
      chaperones hsp70, CCT (TRiC), hsp40, p48 (Hip), and hsp90 were compared on the
      basis of their ability to coprecipitate nascent polypeptides, both before and
      after chemical cross-linking. By all three approaches, hsp70 was found to be the
      predominant chaperone bound to nascent polypeptides. The interaction between
      hsp70 and nascent polypeptides is apparently dynamic under physiological
      conditions but can be stabilized by depletion of ATP or by cross-linking. The
      cytosolic chaperonin CCT was found to bind primarily to full-length, newly
      synthesized actin, and tubulin. We demonstrate and caution that nascent
      polypeptides have a propensity for binding many proteins nonspecifically in cell
      lysates. Although current models of protein folding in vivo have described
      additional components in contact with nascent polypeptides, our data indicate
      that the hsp70 and, perhaps, the hsp90 families are the predominant classes of
      molecular chaperones that interact with the general population of cytosolic
      nascent polypeptides.

PMID- 9285824
TI  - Three determinants in ezrin are responsible for cell extension activity.
AB  - The ERM proteins--ezrin, radixin, and moesin--are key players in membrane
      cytoskeleton interactions. In insect cells infected with recombinant
      baculoviruses, amino acids 1-115 of ezrin were shown to inhibit an actin- and
      tubulin-dependent cell-extension activity located in ezrin C-terminal domain
      (ezrin310-586), whereas full-length ezrin1-586 did not induce any morphological
      change. To refine the mapping of functional domains of ezrin, 30 additional
      constructs were overexpressed in Sf9 cells, and the resulting effect of each was
      qualitatively and semiquantitatively compared. The removal of amino acids 13-30
      was sufficient to release a cell-extension phenotype. This effect was abrogated
      if the 21 distal-most C-terminal amino acids were subsequently deleted (ezrin31
      565), confirming the existence of a head-to-tail regulation in the whole
      molecule. Surprisingly, the deletion in full-length ezrin of the same 21 amino
      acids provided strong cell-extension competence to ezrin1-565, and this property
      was recovered in N-terminal constructs as short as ezrin1-310. Within ezrin1-310,
      amino acid sequences 13-30 and 281-310 were important determinants and acted in
      cooperation to induce cytoskeleton mobilization. In addition, these same residues
      are part of a new actin-binding site characterized in vitro in ezrin N-terminal
      domain.

PMID- 9285826
TI  - A role for the SHP-2 tyrosine phosphatase in nerve growth-induced PC12 cell
      differentiation.
AB  - SHP-1 and SHP-2 are intracellular protein tyrosine phosphatases containing two
      adjacent src homology 2 domains that target these phosphatases to cell surface
      receptor signaling complexes and play a role in receptor signal transduction. In
      this report the PC12 cell system was used to investigate the potential roles of
      SHP-1 and SHP-2 in the induction of neuronal differentiation by nerve growth
      factor (NGF). By using neurite outgrowth as a marker for differentiation, the
      effects of transfected constructs of SHP-1 and SHP-2 were assessed.
      Overexpression of a catalytically inactive SHP-2, but not a catalytically
      inactive SHP-1, blocked NGF-stimulated neurite outgrowth. The mitogen-activated
      protein kinase (MAPK) signaling cascade is important for the morphological
      differentiation in PC12 cells, and both SHP-1 and SHP-2 have been implicated to
      act upstream of MAPK in other receptor signaling systems. A positive role for SHP
      2 but not SHP-1 in the activation of MAPK by NGF was demonstrated by introduction
      of the SHP-2 phosphatase mutants along with hemagglutinin-tagged MAPK.
      Coexpression studies with the SHP-2 mutant along with mutant forms of MAPK kinase
      suggested that SHP-2 functions upstream of MAPK kinase and MAPK in NGF-induced
      neurite outgrowth.

PMID- 9285827
TI  - Mcm2 and Mcm3 are constitutive nuclear proteins that exhibit distinct isoforms
      and bind chromatin during specific cell cycle stages of Saccharomyces cerevisiae.
AB  - The Mcm2-7 proteins are a family of conserved proteins whose functions are
      essential for the initiation of DNA synthesis in all eukaryotes. These patients
      are constitutively present in high abundance in actively proliferating cells. In
      Saccharomyces cerevisiae, the intracellular concentrations of Mcms are between
      100 and 500 times the number of replication origins. However, these proteins are
      limiting for the initiation of DNA synthesis at replication origins. Our studies
      indicate that only a small fraction of Mcm2 and Mcm3 tightly associates with
      chromatin, from late M phase to the beginning of the S phase. The rest of the
      Mcm2 and Mcm3 proteins are disturbed to both the cytoplasm and nucleoplasm in
      relatively constant levels throughout the cell cycle. We also show that S.
      cerevisiae Mcm3 is a phosphoprotein that exists in multiple isoforms and that
      distinct isoforms of Mcm2 and Mcm3 can be detected at specific stages of the cell
      cycle. These results suggest that the localization and function of the Mcm
      proteins are regulated by posttranslational phosphorylation in a manner that is
      consistent with a role for the Mcm proteins in restricting DNA replication to
      once per cell cycle.

PMID- 9285828
TI  - Regulated nuclear translocation of the Mig1 glucose repressor.
AB  - Glucose represses the transcription of many genes in bakers yeast (Saccharomyces
      cerevisiae). Mig1 is a Cys2-His2 zinc finger protein that mediates glucose
      repression of several genes by binding to their promoters and recruiting the
      general repression complex Ssn6-Tup1. We have found that the subcellular
      localization of Mig1 is regulated by glucose. Mig1 is imported into the nucleus
      within minutes after the addition of glucose and is just as rapidly transported
      back to the cytoplasm when glucose is removed. This regulated nuclear
      localization requires components of the glucose repression signal transduction
      pathway. An internal region of the protein separate from the DNA binding and
      repression domains is necessary and sufficient for glucose-regulated nuclear
      import and export. Changes in the phosphorylation status of Mig1 are coincident
      with the changes in its localization, suggesting a possible regulatory role for
      phosphorylation. Our results suggest that a glucose-regulated nuclear import
      and/or export mechanism controls the activity of Mig1.

PMID- 9285829
TI  - The carboxyl-terminal valine residues of proTGF alpha are required for its
      efficient maturation and intracellular routing.
AB  - Soluble forms of transforming growth factor-alpha (TGF alpha) are derived by
      proteolytic processing of an integral membrane glycoprotein precursor (pro TGF
      alpha). Previous studies indicated that phorbol ester-induced cleavage of pro TGF
      alpha in CHO cells is dependent on the presence of a valine residue located at
      the carboxyl terminus of the precursor's cytoplasmic domain. We reassessed this
      requirement with epitope-tagged constructs introduced into transformed rat liver
      epithelial cells that normally express and process TGF alpha. We found that pro
      TGF alpha mutants lacking the terminal valine residues showed greatly reduced
      maturation to the fully glycosylated form. Additionally, they were present at
      substantially reduced levels on the cell surface and, instead, accumulated in the
      endoplasmic reticulum. Consistent with these results, enzyme-linked immunosorbent
      assay (ELISA) and Western blot analyses revealed little or no soluble TGF alpha
      in medium conditioned by cells expressing the mutant constructs. Finally, a
      truncated pro TGF alpha mutant lacking most of the cytoplasmic domain but
      retaining a carboxyl-terminal valine was processed and cleaved in a near-normal
      manner. These results, some of which were reproduced in CHO cells, indicate that
      the predominant effect of the carboxyl-terminal valines is to ensure normal
      maturation and routing of the precursor.

PMID- 9285831
TI  - [Mechanisms of estrogen-induced carcinogenesis--detection of DNA adducts in
      cultured mammalian cells by 32P-postlabeling].
AB  - Estrogens are clearly carcinogenic in humans and rodents, but the mechanisms by
      which these hormones induce cancer are only partially understood. Stimulation of
      cell proliferation and gene expression by binding to the estrogen receptor is one
      important mechanism in hormonal carcinogenesis; however, estrogenicity is not
      sufficient to explain the carcinogenic activity of all estrogens because some
      estrogens are not carcinogenic. Estrogens are nonmutagenic in many assays, but
      exhibit specific types of genotoxic activity under certain conditions. We have
      studied extensively the mechanisms by which estrogens induce neoplastic
      transformation in a model in vitro system. Diethylstilbestrol (DES) and 17 beta
      estradiol (E2) and their metabolites induce morphological and neoplastic
      transformation of Syrian hamster embryo (SHE) cells that express no measurable
      levels of estrogen receptor. The estrogens induce DNA adduct formation that is
      detected by 32P-postlabeling. DNA adduct formation is detected in cells treated
      with DES, but not in cells treated with either alpha- or beta-dienestrol.
      Similarly, morphological transformation of SHE calls is induced by treatment with
      DES, but not by treatment with alpha- or beta-dienestrol. Exposure of SHE
      treatment cells to E2 and its metabolites 2-hydroxyestradiol and 4
      hydroxyestradiol leads to covalent DNA adduct formation, corresponding to the
      induction of cell transformation. Induction of morphological transformation of
      SHE cells by estrogens correlates well with the ability of estrogens to induce
      DNA adduct formation. DNA damage caused by DNA adduct formation may be important
      in hormonal carcinogenesis. It is clear that hormones affect carcinogenesis by
      epigenetic mechanisms such as stimulation of cell proliferation of estrogen
      dependent target cells and reprogramming of cellular differentiation and gene
      expression. In addition, significant evidence exists that certain estrogens can
      also cause genetic alterations by mechanisms not involving the classic estrogen
      receptor. These findings indicate that hormonal carcinogenesis is most likely a
      result of the interplay of both genetic and epigenetic factors.

PMID- 9285832
TI  - [A new model of delayed healing of acetic acid ulcers in rats by indomethacin via
      osmotic pump].
AB  - Gastric ulcers were produced in male Donryu rats (8-weeks-old) by subserosal
      injection of 20 microliters of 20% acetic acid. Five days later, an indomethacin
      (IND)-filled osmotic pump (OP) was implanted into the dorsal subcutaneous space
      in the rats and maintained for 2, 3 or 4 weeks. The natural healing of the acetic
      acid-induced ulcers was significantly (P < 0.05) delayed by administration of IND
      via OP implanted for 4 weeks. Two, 3 and 4 weeks after OP implantation, the
      plasma IND levels was 1.87 +/- 0.13, 2.43 +/- 0.16 and 0.74 +/- 0.26
      (micrograms/ml), respectively, showing that a steady state IND plasma level was
      maintained for 3 weeks. The gastric mucosal PGE2 levels in rats with ulcers for 3
      weeks after implantation of OP were significantly (P < 0.05) reduced by IND (IND(
      ):576.6 +/- 83.9 pg/mg, IND(+):355.6 +/- 34.7 pg/mg). Repeated administration of
      enprostil, famotidine and rabeprazole at 25 micrograms/kg, 100 mg/kg and 10 mg/kg
      (p.o., b.i.d.), respectively, showed anti-ulcer activity. Teprenone and
      rebamipide had only slight anti-ulcer activity. These findings indicated that
      this model of delayed healing of acetic acid ulcers by IND using OP is useful for
      investigating the anti-ulcer activity of drugs.

PMID- 9285830
TI  - A dependent pathway of cytoplasmic polyadenylation reactions linked to cell cycle
      control by c-mos and CDK1 activation.
AB  - During oocyte maturation and early development, mRNAs receive poly(A) in the
      cytoplasm at distinct times relative to one another and to the cell cycle. These
      cytoplasmic polyadenylation reactions do not occur during oogenesis, but begin
      during oocyte maturation and continue throughout early development. In this
      report, we focus on the link between cytoplasmic polyadenylation and control of
      the cell cycle during meiotic maturation. Activation of maturation promoting
      factor, a complex of CDK1 and cyclin, is required for maturation and dependent on
      c-mos protein kinase. We demonstrate here that two classes of polyadenylation
      exist during oocyte maturation, defined by their dependence of c-mos and CDK1
      protein kinases. Polyadenylation of the first class of mRNAs (class I) is
      independent of c-mos and CDK1 kinase activities, whereas polyadenylation of the
      second class (class II) requires both of these activities. Class I
      polyadenylation, through its effects on c-mos mRNA, is required for class II
      polyadenylation. cis-acting elements responsible for this distinction reside in
      the 3'-untranslated region, upstream of the polyadenylation signal AAUAAA.
      Cytoplasmic polyadenylation elements (CPEs) are sufficient to specify class I
      polyadenylation, and subtle changes in the CPE can substantially, though not
      entirely, shift an RNA from class I to class II. Activation of class I
      polyadenylation events is independent of hyperphosphorylation of CPE-binding
      protein or poly(A) polymerase, and requires cellular protein synthesis. The two
      classes of polyadenylation and of mRNA define a dependent pathway, in which
      polyadenylation of certain mRNAs requires the prior polyadenylation of another.
      We propose that this provides one method of regulating the temporal order of
      polyadenylation events, and links polyadenylation to the control of the meiotic
      cell cycle.

PMID- 9285834
TI  - [Pharmacology and Internet].

PMID- 9285833
TI  - [Anti-allergic activity of betotastine besilate (TAU-284), a new anti-allergic
      drug].
AB  - The anti-allergic activity of betotastine besilate (betotastine), a new anti
      allergic drug, was investigated in several allergy models of rats in comparison
      with other anti-allergic drugs.1) Orally administered betotastine (0.1-30 mg/kg)
      inhibited homologous passive cutaneous anaphylaxis (PCA) in rats in a dose
      dependent manner (ID30-value: 0.38 mg/kg). The inhibitory activity of betotastine
      was significant at 1 mg/kg and was more potent than that of ketotifen,
      terfenadine, cetirizine and epinastine. The PCA-inhibitory activity of
      betotastine lasted more than 8 hr after administration, and the repeated
      administration of betotastine lasted more than not induce drug-tolerance. 2)
      Orally administered betotastine inhibited the histamine-induced skin reaction in
      rats in a dose-dependent manner (ID30:0.10 mg/kg), and the inhibitory activity
      lasted more than 4 hr after the administration. Its inhibitory activity was
      significant at 0.1 and 1 mg/kg and was more potent than those of ketotifen,
      terfenadine, cetirizine and epinastine. 3) Betotastine suppressed histamine
      release from rat peritoneal mast cells at a high concentration (10(3)(10(-3)M).
      These results suggest that betotastine has a potent and long acting anti-allergic
      activity, and these effects are mainly due to histamine antagonistic activity.

PMID- 9285836
TI  - Prediction equations do not eliminate systematic error in self-reported body mass
      index.
AB  - Epidemiological studies of the risks of obesity often use body mass index (BMI)
      calculated from self-reported height and weight. The purpose of this study was to
      examine the pattern of reporting error associated with self-reported values of
      BMI and to evaluate the extent to which linear regression models predict measured
      BMI from self-reported data and whether these models could compensate for this
      reporting error. We examined measured and self-reported weight and height on 5079
      adults aged 30 years to 64 years from the second National Health and Nutrition
      Examination Survey. Measured and self-reported BMI (kg/m2) was calculated, and
      multiple linear regression techniques were used to predict measured BMI from self
      reported BMI. The error in self-reported BMI (self-reported BMI minus measured
      BMI) was not constant but varied systematically with BMI. The correlation between
      measured BMI and the error in self-reported BMI was -0.37 for men and -0.38 for
      women. The pattern of reporting error was only weakly associated with self
      reported BMI, with the correlation being 0.05 for men and -0.001 for women. Error
      in predicted BMI (predicted BMI minus measured BMI) also varied systematically
      with measured BMI, but less consistently with self-reported BMI. More complex
      models only slightly improved the ability to predict measured BMI compared with
      self-reported BMI alone. None of the equations were able to eliminate the
      systematic reporting error in determining measured BMI values from self-reported
      data. The characteristic pattern of error associated with self-reported BMI is
      difficult or impossible to correct by the use of linear regression models.

PMID- 9285835
TI  - Prejudice toward fat people: the development and validation of the antifat
      attitudes test.
AB  - Although the stigma of obesity in our society is well documented, the measurement
      of antifat attitudes has been a difficult undertaking. Two studies were conducted
      to construct and validate the Antifat Attitudes Test (AFAT). In study 1, college
      students (110 men and 175 women) completed the preliminary 54-item AFAT and
      specific indices of body image and weight-related concerns. Psychometric and
      factor analysis revealed a 47-item composite scale and three internally
      consistent factors that were uncorrelated with social desirability:
      Social/Character Disparagement, Physical/Romantic Unattractiveness, and Weight
      Control/Blame. Several body images correlates of antifat prejudice were
      identified, and men expressed more negative attitudes than women. Study 2
      experimentally examined the effects of information about the controllability of
      weight on the antifat attitudes of 120 participants. Exposure to information on
      behavioral vs. biogenetic control led to greater blame of persons who are fat for
      their body size. The implications of the findings and the potential utility of
      the AFAT are discussed.

PMID- 9285838
TI  - Resting metabolic rate in African-American and Caucasian girls.
AB  - Recent studies have found a lower resting metabolic rate (RMR) in African
      American (AA) women with obesity as compared with Caucasian (C) women with
      obesity. It is unknown if this difference in RMR is seen in prepubertal girls or
      in those of average body weight. Therefore, we studied RMR in 21 AA and 24 C
      girls, ages 7-10, who were well matched for age, weight, body mass index (BMI),
      and pubertal status. All had BMI between 15% and 85% for age and race, based on
      data from the First National Health and Nutrition Examination Survey. Fat free
      mass (FFM) was measured by dual-energy X-ray absorptiometry. RMR was measured
      with a Deltatrac indirect calorimeter under controlled conditions after the
      subjects underwent an overnight fast. The slopes of the regression equations were
      similar for both groups (p = 0.7). After adjustment for FEM, the AA girls had a
      significantly lower RMR than did the C girls (-92 +/- 32 kcal/d, p = 0.007 by
      analysis of covariance). This significance was maintained after exclusion of
      total body bone mineral content. These data suggest that normal-weight
      prepubertal AA girls may have reduced resting energy expenditure compared with C
      girls.

PMID- 9285837
TI  - Sagittal diameter minus subcutaneous thickness. An easy-to-obtain parameter that
      improves visceral fat prediction.
AB  - Two groups of 99 and 98 women were studied to test if correcting sagittal
      diameter by subtracting the thickness of subcutaneous abdominal adipose tissue
      improves its degree of association with visceral adipose tissue. The first group
      (age, 40 +/- 14 years; body mass index [BMI], 36 +/- 6 kg/m2) was used to
      calculate the predictive equations for visceral adipose tissue. The second group
      (age, 43 +/- 14 years; BMI, 37 +/- 6 kg/m2) was used for cross-validation.
      Various anthropometric parameters were measured by ultrasound and computed
      tomography. Correlation coefficients with single-slice visceral adipose tissue
      area, after sagittal diameter was corrected by subtracting subcutaneous
      thickness, rose from 0.63 to 0.72 in the first group and from 0.64 to 0.71 in the
      second group. The standard error of residuals of the regression formula for
      visceral adipose tissue area was 10% lower with modified sagittal diameter than
      with sagittal diameter alone. During cross-validation, the standard error of
      differences was 5% lower with modified sagittal diameter. The visceral adipose
      tissue estimate was also less biased by the size of the area when sagittal
      diameter minus subcutaneous thickness was used. Results show that subtracting the
      thickness of abdominal subcutaneous adipose tissue from sagittal diameter
      significantly improves the predictive power of sagittal diameter for visceral
      adipose tissue and could be a useful tool for epidemiological studies.

PMID- 9285839
TI  - Genetic influences on changes in body mass index: a longitudinal analysis of
      women twins.
AB  - Numerous studies have demonstrated genetic influences on body fat, but there also
      may be genetic effects on its intraindividual variation over time. This study
      examined changes in body mass index (BMI) using longitudinal data from two
      examinations of the Kaiser Permanente Women Twins Study, performed a decade
      apart. The analysis included 630 women, 185 monozygotic and 130 dizygotic twin
      pairs, with average ages of 41 years and 51 years at the two examinations,
      respectively. Age-adjusted heritability estimates for the change in BMI over the
      decade ranged from 0.57 to 0.86 (all p < or = 0.001) using three different
      statistical analysis approaches, indicating that at least half and possibly as
      much as 85%+, of the variance in the change in BMI is attributable to genetic
      influences under a polygenic model. These estimates remained statistically
      significant after adjusting for environmental factors (ranging from 0.57 to 0.78)
      and with additional adjustment for BMI at baseline (ranging from 0.41 to 0.79),
      although dizygotic intraclass correlations were low after these adjustments.
      Thus, in addition to known environmental and behavioral influences, these results
      provide evidence for genetic influences on changes in BMI over a decade in women.

PMID- 9285840
TI  - Effects of visceral fat and weight loss on lipoprotein(a) concentration in
      subjects with obesity.
AB  - We studied the relationships between regional body fat distribution and metabolic
      variables with lipoprotein(a) [Lp(a)] as well as the effects of weight loss on
      Lp(a) in 25 women and 9 men with obesity. Regional body fat distribution, as
      evaluated by the use of computed tomography; Lp(a); and fasting glucose, insulin,
      cholesterol, and triglycerides were analyzed before and after a very low-energy
      diet. No significant correlations were found between visceral, subcutaneous, and
      total fat and Lp(a) or between metabolic variables and Lp(a). All anthropometric
      variables significantly decreased after a very low-energy diet. Fasting glucose,
      insulin, triglycerides, and cholesterol significantly decreased after a very low
      energy diet. No significant changes in Lp(a) concentration after a very low
      energy diet were found. The correlation between the initial values of Lp(a) and
      changes of Lp(a) after a very low-energy diet was slightly significant (rho =
      0.33, p < 0.06). In conclusion, our study shows that Lp(a) is not influenced by
      obesity, visceral fat, metabolic variables, or weight loss induced by a very low
      energy diet.

PMID- 9285841
TI  - Relationship between muscle sympathetic nerve activity and plasma leptin
      concentration.
AB  - In humans, basal muscle sympathetic nerve activity (MSNA), a direct measure of
      sympathetic nervous outflow, is correlated with percentage of body fat. The
      underlying physiological mechanism is unknown. On the basis of the observation
      that leptin increases sympathetic nervous outflow in the ob/ob mouse, we
      hypothesized that leptin, a hormone secreted by the adipose tissue, may act as a
      peripheral signal to increase sympathetic nervous outflow from the central
      nervous system. We therefore tested whether basal MSNA is correlated with plasma
      leptin concentration. Fasting plasma samples and recordings of basal MSNA in the
      peroneal nerve were obtained from 37 healthy, nondiabetic men (35 whites and 2
      Mexican-Americans; 29 +/- 7 years, 86 +/- 14 kg, 24 +/- 10% body fat; mean +/-
      SD) who were fed a weight-maintenance diet on a metabolic ward. As expected,
      plasma leptin concentration (geometric mean, 6.4 ng/mL; 95% confidence interval,
      4.6 ng/mL to 9.0 ng/mL) correlated with % body fat (r = 0.93, p < 0.001). Basal
      MSNA was 31.6 +/- 10.0 bursts/min and correlated with % body fat (r = 0.53, p <
      0.001) and with plasma leptin concentration (r = 0.44, p < 0.01). In conclusion,
      the results demonstrate a correlation between MSNA and plasma leptin
      concentration of a magnitude similar to that between MSNA and % body fat. Leptin
      may therefore be the peripheral signal explaining the correlation between MSNA
      and % body fat. A full understanding of the relationship between leptin and the
      activity of the sympathetic nervous system requires further studies, including
      the administration of leptin in humans.

PMID- 9285842
TI  - A low sympathoadrenal activity is associated with body weight gain and
      development of central adiposity in Pima Indian men.
AB  - To investigate the possible role of impaired sympathetic nervous system and/or
      adrenal medullary function in the etiology of human obesity, we studied 64 Pima
      Indian men (28 +/- 6 years, 101 +/- 25 kg, 34 +/- 9% body fat, mean +/- SD) in
      whom sympathoadrenal function was estimated at baseline by measurements of 24
      hour urinary norepinephrine (NE) and epinephrine (Epi) excretion rates under
      weight-maintenance conditions. Body weight, body composition (hydrodensitometry),
      and body fat distribution (waist-to-thigh circumference ratio, W/T) were measured
      at baseline and follow-up. Follow-up data were available on 44 subjects who
      gained on average 8.4 +/- 9.5 kg over 3.3 +/- 2.1 years. In these subjects,
      baseline NE excretion rate, adjusted for its determinants (i.e., fat free mass,
      fat mass, and W/T), correlated negatively with bodyweight gain (r = -0.38; p =
      0.009). Baseline Epi excretion rate correlated negatively with changes in W/T (r
      = -0.44; p = 0.003). In conclusion, our data show for the first time that a flow
      sympathetic nervous system activity is associated with body weight gain in
      humans. Also, a low activity of the adrenal medulla is associated with the
      development of central adiposity.

PMID- 9285843
TI  - Running exercise improves metabolic abnormalities and fat accumulation in sucrose
      induced insulin-resistant rats.
AB  - Insulin resistance and hyperinsulinemia are observed in rats fed a high sucrose
      diet. Insulin resistance is thought to be related to abnormal fat distribution.
      We previously reported the metabolic characteristics and the fat distribution in
      rats with sucrose-induced insulin resistance. This study was designed to examine
      the effects of exercise in these rats. The rats were divided into three groups:
      those receiving a starch-based diet (control), those receiving a high-sucrose
      diet (sucrose fed), and those receiving a high-sucrose diet and wheel-running
      exercise (exercised). Animals were killed after 4 weeks or 12 weeks. After 4
      weeks, the three groups did not differ with respect to gain in adipose tissues.
      The portal vein (PV) insulin concentration was significantly increased in the
      sucrose-fed and the exercised rats compared with the control rats. The inferior
      vena cava (IVC) glucose concentration and the PV free fatty acid (FFA) were
      significantly lower in the exercised rats than in the sucrose-fed rats. After 12
      weeks, the exercised rats had significantly lower mesenteric fat (MS) and
      subcutaneous fat (SC) and a lower MS:SC ratio than the sucrose-fed rats. The
      glucose levels in IVC, PV, and FFA in PV were significantly reduced in the
      exercised rats as compared with the sucrose-fed rats. These findings suggest that
      long-term exercise improves insulin resistance by reducing the accumulation of MS
      as well as SC. It is also suggested that short-term exercise improves glucose
      metabolism without change of fat accumulation.

PMID- 9285844
TI  - Cardiac autonomic nervous system activity in obese and never-obese young men.
AB  - Autonomic nervous system (ANS) activity in age-matched, weight-stable, free
      living, ad libitum-fed, obese (OB) and never-obese (NO) young men (body mass
      index means [SD], 38.5 [3.9] and 22.0 [1.7], respectively) was evaluated by
      sequential blockade of cardiac autonomic innervation with weight-adjusted doses
      of parasympathetic (atropine) and sympathetic (esmolol) blockers so as to produce
      maximal effects on heart rate. Change in heart period (interbeat interval) from
      baseline, induced by atropine, defined parasympathetic control (PC), and the
      subsequent change, after esmolol administration, defined sympathetic control
      (SC). The heart period, after PC and SC blockade, defined intrinsic heart period
      (I). In the OB group, baseline heart period and PC were lower, and SC and I were
      higher, than in the NO group. The results in the OB, relative to the NO subjects,
      are similar to those reported in a previous study of NO subjects who had
      undergone a 10% weight gain by overfeeding. These findings suggest that the ANS
      of individuals with obesity is chronically altered in a way that would tend to
      oppose their excessive adiposity, and that these autonomic changes are more
      likely to be responses to other forces that induce obesity, rather than being
      primary agents in the production of the disease.

PMID- 9285845
TI  - Enterostatin--a peptide regulating fat intake.
AB  - A high fat intake, together with an inability to match lipid oxidation to fat
      intake, has been found to be correlated with obesity in humans. This review
      describes our current understanding of enterostatin, a peptide that selectively
      reduces fat intake. Enterostatin is formed in the intestine by the cleavage of
      secreted pancreatic procolipase, the remaining colipase serving as an obligatory
      cofactor for pancreatic lipase during fat digestion. Enterostatin is also
      produced in the gastric mucosa and the mucosal epithelia of the small intestine.
      Procolipase gene transcription and enterostatin release into the gastrointestinal
      lumen are increased by high-fat diets. After feeding, enterostatin appears in the
      lymph and circulation. Enterostatin will selectively inhibit fat intake during
      normal feeding and in experimental paradigms that involve dietary choice. Its
      anorectic effect has been demonstrated in a number of species. Both peripheral
      and central sites of action have been proposed. The peripheral mechanism involves
      an afferent vagal signaling pathway to hypothalamic centers. The central
      responses are mediated through a pathway that includes both serotonergic and
      opioidergic components. Chronically, enterostatin reduces fat intake, bodyweight,
      and body fat. This response may involve multiple metabolic effects of
      enterostatin, which include a reduction of insulin secretion, an increase in
      sympathetic drive to brown adipose tissue, and the stimulation of adrenal
      corticosteroid secretion. A possible pathophysiological role is suggested by
      studies that have linked low enterostatin production and/or responsiveness to
      strains of rat that become obese and prefer dietary fat. Humans with obesity also
      exhibit a lower secretion of pancreatic procolipase after a test meal, compared
      with persons of normal weight.

PMID- 9285846
TI  - Amino acids, protein, and body weight.

PMID- 9285847
TI  - Brain serotonin content: physiological regulation by plasma neutral amino acids.
      1971.

PMID- 9285848
TI  - Relationship between serum amino acid concentration and fluctuations in appetite.
      1956.

PMID- 9285850
TI  - Enteric nervous system: intestinal absorption and secretion.

PMID- 9285849
TI  - Neuro-enteric mechanisms of gastrointestinal motor function.

PMID- 9285851
TI  - Gluten sensitivity and neurological illness.

PMID- 9285852
TI  - Influence of nutrition on psychomotor development.

PMID- 9285853
TI  - Pediatric functional gastrointestinal disorders.

PMID- 9285854
TI  - Cyclic vomiting syndrome: a paroxismal disorder of brain-gut interaction.

PMID- 9285855
TI  - Recurrent abdominal pain and irritable bowel syndrome in children.

PMID- 9285857
TI  - Gastrointestinal disorders in muscular dystrophies.

PMID- 9285856
TI  - Pharmacotherapy of altered brain-gut interactions in functional gastrointestinal
      disorders.

PMID- 9285858
TI  - Cerebral palsy and gut functions.

PMID- 9285859
TI  - Autonomic gastroenteric disorders in children due to lesions of cranial nerve
      nuclei, spinal cord and peripheral innervation.

PMID- 9285860
TI  - Aganglionosis and other neuromuscular dysfunctions.

PMID- 9285861
TI  - Genetic aspects of neurocristopathies.

PMID- 9285862
TI  - Effects of neurological diseases on body composition and energy metabolism.

PMID- 9285863
TI  - Swallowing disorders and rehabilitation techniques.

PMID- 9285864
TI  - Diagnostic and therapeutic approach to vomiting and gastroparesis in children
      with neurological and neuromuscular handicap.

PMID- 9285865
TI  - Chronic constipation and fecal incontinence in children with neurological and
      neuromuscular handicap.

PMID- 9285866
TI  - Guidelines for school and community programs to promote lifelong physical
      activity among young people. National Center for Chronic Disease Prevention and
      Health Promotion, Centers for Disease Control and prevention.
AB  - Regular physical activity is linked to enhanced health and to reduced risk for
      all-cause mortality and the development of many chronic diseases in adults.
      However, many U.S. adults are either sedentary of less physically active than
      recommended. Children and adolescents are more physically active than adults, but
      participation in physical activity declines in adolescence. School and community
      programs have the potential to help children and adolescents establish lifelong,
      healthy physical activity patterns. This report summarizes recommendations for
      encouraging physical activity among young people so that they will continue to
      engage in physical activity in adulthood and obtain the benefits of physical
      activity throughout life. These guidelines were developed by CDC in collaboration
      with experts from universities and from national, federal, and voluntary agencies
      and organizations. They are based on an in-depth review of research, theory, and
      current practice in physical education, exercise science, health education, and
      public health. The guidelines include recommendations about 10 aspects of school
      and community programs to promote lifelong physical activity among young people
      policies that promote enjoyable physical activity and social environments that
      encourage and enable physical activity; physical education curricula and
      instruction; health education curricula and instruction; extracurricular physical
      activity programs that meet the needs and interests of students; involvement of
      parents and guardians on physical activity instruction and programs for young
      people; personnel training; health services for children and adolescents;
      developmentally appropriate community sports and recreation programs that are
      attractive to young people; and regular evaluation of physical activity
      instruction, programs, and facilities.

PMID- 9285867
TI  - Bridging student health risks and academic achievement through comprehensive
      school health programs.
AB  - In the National Action Plan for Comprehensive School Health Education,
      representatives for over 40 health, education, and social service organizations
      viewed education and health as independent systems. Participation concluded that
      healthy children learn better, and they cautioned that no curriculum can
      compensate for deficiencies in student health status. While literature confirms
      the complexity of health issues confronting today's students, schools face
      enormous pressure to improve academic skills. Local school leaders and
      stakeholders often remain unconvinced that improving student health represents a
      means to achieving improved academic outcomes. A rich body of literature confirms
      a direct link between student health risk behavior and education outcomes,
      education behavior, and student attitudes about education. This article
      summarizes relevant information concerning the health risk behavioral categories
      of intentional injuries; tobacco; alcohol, and other drugs; dietary, physical
      activity, and sexual risk behaviors.

PMID- 9285868
TI  - How prospective school health educators can build a portfolio to communicate
      professional expertise.
AB  - Portfolios--purposeful and selective collections of authentic evidence regarding
      teaching and learning--occur increasingly in K-12 classrooms, preservice teacher
      education, and university initiatives to enhance teaching effectiveness of
      faculty. In addition to being used to improve instruction, portfolios can help
      teacher candidates with initial employment. This article describes an organized
      set of materials prospective school health educators should develop to accurately
      represent their newly acquired skills and competencies.

PMID- 9285869
TI  - Evaluating health-related Web sites.
AB  - a growing concern has emerged for the quality of health-related documents
      contained on the World Wide Web. Increased use of the World Wide Web by consumers
      and health education professionals, as well as ease of Web page publication, has
      heightened the need for criteria in Web page construction and evaluation. This
      article reviews and discusses elements to consider in Web page construction and
      evaluation, and provides a form to assist in assessment.

PMID- 9285870
TI  - Preservice elementary teacher's attitudes toward gay and lesbian parenting.
AB  - This preliminary investigation assessed preservice elementary teacher's attitudes
      toward homosexual parents and their children. The study populations included 195
      college students enrolled in an elementary school health methods course at a
      large northeastern university. A 51-item " and Lesbian Parenting Questionnaire"
      was used for data collection purposes. Reliability estimates for the scales were:
      attitudes toward lesbians and gay men (alpha = .90), comfort toward gay and
      lesbian families (alpha = .92), and knowledge about homosexuality (alpha = .52).
      Most respondents agreed gay men: were not disgusting, should be allowed to teach,
      were not perverted, and should not overcome their feelings of homosexuality. Most
      respondents disagreed lesbians cannot fit into society or were sick. Nearly all
      agreed female homosexuality should not be a basis for job discrimination. Females
      were significantly (p < .001) more comfortable with gay or lesbian parents and
      their children than were males. Females had significantly (p < .01) more
      favorable attitudes toward gay fathers than did male respondents. Respondents
      with stronger religious attitudes had significantly (p < .01) more negative
      attitudes toward lesbian parents than respondents with weaker religious
      attitudes.

PMID- 9285871
TI  - Teaching through stories.

PMID- 9285872
TI  - Modular shoulder arthroplasty.
AB  - One hundred consecutive Biomet modular shoulder arthroplasties were studied
      prospectively and were evaluated with a minimum 2-year follow-up (average 41
      months). Fifty-seven women and 43 men with an average age of 64 years were
      evaluated for pain, activities of daily living, range of motion, cost, and
      complications. Fourteen patients had undergone previous surgery to the shoulder.
      Seventy patients underwent total shoulder arthroplasty, and thirty underwent
      hemiarthroplasty. Pain and range of motion demonstrated statistically significant
      improvement. Eight activities of daily living were rated on a 0 to 3 scale, and
      all were significantly improved. Complications were noted in 18 patients and
      included urinary retention, pulmonary embolus, rotator cuff tear, titanium
      synovitis, subluxation, and dislocation. Twelve shoulders underwent secondary
      procedures for rotator cuff repair, open reduction, and component revision for
      instability. Lucent lines were present in 62.5% of glenoids, 92.3% of cemented
      stems, and 0% of cementless stems on postoperative radiographs. No patients
      underwent revision surgery for component loosening, and no cases of humeral head
      stem dissociation were seen. Ninety-five shoulders were rated by the patients as
      improved, and five were made worse.

PMID- 9285873
TI  - Effects of age, testing speed, and arm dominance on isokinetic strength of the
      elbow.
AB  - The strength of active flexion/extension and supination/pronation was measured
      isokinetically in 60 right-hand-dominant nonathletic men. They were equally
      divided into a younger group (20 to 30 years) and an older group (50 to 60 years)
      with moderate occupational and spare-time activity levels. Peak torque, work,
      power, and the angle of peak torque production were measured bilaterally at a
      slow (90 degrees/sec) and a fast (180 degrees/sec) speed of movement. Although
      highly significant differences were found between the young and older groups in
      flexion and extension, no age-related differences were found in supination and
      pronation. The dominant side had significantly higher levels of peak torque,
      work, and power in flexion; however, no significant differences were detected in
      peak torque for extension, supination, and pronation. Isokinetic peak torque and
      work were greater at the slower speed as opposed to power, which was
      significantly greater at the faster speed with the exception of pronation
      movement. With regard to the angle where peak torque was achieved, significant
      differences were detected between groups, which suggests that age appears to
      affect where in the range of motion peak torque is produced.

PMID- 9285874
TI  - Electromyographic and nerve block analysis of the subscapularis liftoff test.
AB  - The inability to perform the "liftoff" test has been attributed to a
      subscapularis muscle or tendon injury. The goals of this study were to evaluate
      the activity of the glenohumeral muscles during performance of the "liftoff"
      maneuver and to identify the most effective initial upper extremity placement
      that isolates the subscapularis musculotendinous unit. In the first phase of this
      study 15 subjects accomplished four proposed versions to the "liftoff" test while
      their intramuscular electromyographic activity in select glenohumeral muscles was
      recorded. The second phase of this study assessed the ability of five subjects
      with a nonfunctional subscapularis musculotendinous unit to perform the same
      proposed versions. On the basis of electromyographic data none of the proposed
      versions to the "liftoff" maneuver isolated the upper and lower subscapularis
      muscle from either the teres major, latissimus dorsi, posterior deltoid, or
      rhomboid muscles (p > 0.05). In the presence of a nonfunctional subscapularis
      musculotendinous unit, the subjects were able to perform all of the proposed
      versions of the "liftoff" maneuver except one: elevation of the dorsum of the
      hand from the posterior-inferior border of the scapula (maximum internal rotation
      test). Although significant electromyographic activity was generated in the
      potentially confounding shoulder girdle muscles during the maximum internal
      rotation "liftoff" test, a successful test appears to be dependent on the
      isolated glenohumeral internal rotation function of the subscapularis muscle.

PMID- 9285875
TI  - Inferior subluxation of the humeral head after trauma or surgery.
AB  - Inferior subluxation of the humeral head can occur after shoulder trauma or
      surgery. One hundred consecutive patients were evaluated prospectively after
      shoulder surgery or injury. The radiographic incidence of inferior subluxation of
      the humeral head 2 weeks after rotator cuff repair was 10%. The radiographic
      incidence of inferior subluxation after fracture of the proximal humerus was 42%,
      and the incidence 2 weeks after prosthetic humeral head replacement was 60%. The
      immediate postoperative radiograph showed an inferior subluxation of the humeral
      head in 4% of patients after prosthesis insertion, but no subluxations were seen
      immediately after rotator cuff repair. Radiographs made immediately after
      fracture of the humerus showed a 16% incidence of inferior subluxation. The
      inferior subluxation resolved by 6 weeks in 92% of patients with humeral
      fractures, 96% of patients with humeral head prostheses, and all patients who had
      undergone rotator cuff repair. No subluxations were seen 2 years after injury or
      surgery. The treatment used--early active exercises and a sling when not
      exercising--was effective.

PMID- 9285876
TI  - Electromyography of shoulder muscles in relation to force direction.
AB  - In a static force task the electromyographic level of 14 shoulder muscles
      including 3 rotator cuff muscles was related to force direction. Surface and wire
      electrodes were used. The force direction of maximal electromyography (principal
      action) was identified for every muscle. The principal action expresses the
      function of a muscle in a special situation. The deltoid was active in a force
      direction that could be understood from its anatomy. The trapezius and serratus
      were mainly involved in stabilizing the scapula in upward and outward force
      directions. Large multiarticular muscles such as the pectoralis and the
      latissimus were active in downward and forward forces. The rotator cuff seems to
      have a specific role in stabilizing the glenohumeral joint. These data can be
      compared with data of patients with shoulder disorders and with kinematic data of
      a shoulder model.

PMID- 9285877
TI  - Active and passive factors in inferior glenohumeral stabilization: a
      biomechanical model.
AB  - This study examines the stabilizing factors of the glenohumeral joint against
      inferior translation over a range of subluxations. Factors examined included the
      glenohumeral capsular ligaments, the coracohumeral ligament, the rotator cuff
      forces, and the long head of the biceps force. Simulated muscle forces were
      applied to eight shoulder specimens with the arm near 0 degrees abduction.
      Stability was defined as the force required to inferiorly sublux the joint to a
      specified translation from the centered position and was evaluated under varying
      configurations of capsule cuts, humeral rotation, and muscle loads. The
      supraspinatus and biceps muscle forces were found to be important active
      stabilizers. Thus, tension in the long head of the biceps did not tend to depress
      the humeral head. The inferior glenohumeral ligament was an important passive
      stabilizer in external rotation. Understanding the effects of these factors adds
      insight into the underlying biomechanics of clinical shoulder instability.

PMID- 9285878
TI  - Type 2 fractures of the distal clavicle: a new surgical technique.
AB  - Neer type 2 fractures of the distal clavicle have a high rate of nonunion and
      delayed union. In this series nine cases of coracoclavicular ligament
      reconstruction with Dacron graft material led to union at the fracture site. All
      patients had no symptoms and returned to full activity. This technique allows for
      stable fixation with early mobilization and return to work and sports.

PMID- 9285880
TI  - Delayed onset of posterior interosseous nerve palsy after distal biceps tendon
      repair.

PMID- 9285879
TI  - Arthroscopic repair of glenolabral injuries with an absorbable fixation device.
AB  - In view of potential problems with metallic implants around the shoulder a
      bioabsorbable tact has been used in arthroscopic repair of labral lesions in the
      shoulder joint. We report on a consecutive series of 70 patients (71 shoulders)
      who had arthroscopic stabilization of Bankart lesions, SLAP lesions, and other
      labral detachments with the Suretac device. Minimum follow-up time was 12 months
      (range 12 to 27 months). Clinical outcome was assessed with the Constant score.
      The recurrence of dislocation or subluxation in the 42 unstable shoulders was 12%
      (5 of 42), and in 78% (33 of 42) the Constant score was rated good or excellent.
      The recurrence of dislocation in true anteroinferior dislocators was 3.2% (1 of
      31). A total of 82.3% (14 of 17) of patients with SLAP repairs were rated good or
      excellent, and 53% (9 of 17) returned to their preinjury level of sporting
      activities. Eight (67%) of 12 patients with labral detachments other than Bankart
      and SLAP lesions were rated good or excellent, and 64% (7 of 11) returned fully
      to sports.

PMID- 9285882
TI  - Pigmented villonodular synovitis of the subacromial bursa.

PMID- 9285881
TI  - Osteoid osteoma of the clavicle.

PMID- 9285883
TI  - Posterolateral rotatory instability of the elbow after posttraumatic cubitus
      varus.

PMID- 9285884
TI  - Ganglion of the acromioclavicular joint.

PMID- 9285885
TI  - Zinc metabolism in non-insulin dependent diabetes mellitus.
AB  - Low plasma zinc concentrations and increased zinc excretion have been reported in
      patients with non-insulin dependent diabetes mellitus (NIDDM). This study was
      designed to compare zinc metabolism in ten NIDDM patients with ten healthy
      controls, using stable isotopes of zinc. Zinc absorption from a standard
      breakfast labelled extrinsically with 3 mg 67Zn was measured using a fecal
      monitoring technique and thermal ionization quadrupole mass spectrometry. One
      hour after the test meal each volunteer was given 0.5 mg 70Zn (as citrate)
      intravenously and blood samples taken at intervals for up to 6 days. Isotopic
      enrichment was measured and the data entered into a simple kinetic model to
      estimate the size and rate of turnover of exchangeable pools of zinc. Urinary
      zinc excretion was higher in the male diabetics than controls (p < 0.05), but not
      in females. Since the efficiency of absorption and endogenous losses of zinc were
      very variable between individuals, and there was only a limited amount of data,
      it was not possible to draw conclusion about the effect of NIDDM on zinc
      absorption and excretion. However, the fact that there were no differences in
      exchangeable zinc pool sizes suggests that zinc metabolism is not altered in
      NIDDM.

PMID- 9285886
TI  - Binding of endogenous and exogenous cadmium to glutelin in rice grains as studied
      by HPLC/ICP-MS with use of a stable isotope.
AB  - Cadmium (Cd) in polished rice grains was extracted under various conditions and
      the chemical forms of the metal in soluble fractions were determined together
      with copper, zinc and other metals by HPLC with on-line detection by inductively
      coupled argon plasma (ICP)--mass spectrometry (MS). Cd (753 ng/g) in rice grains
      grown in Cd-contaminated rice fields was mostly bound to glutelin in soluble
      fractions. Binding of Cd in vitro to constituents in rice grains was examined by
      incubating CdCl2 enriched with 113Cd (96.3% enrichment) in a suspension of
      powdered rice grains. Distributions of exogenous 113Cd in the soluble fraction of
      Cd-contaminated rice grains was identical with that of endogenous Cd on a size
      exclusion column, and the metal was shown to bind to glutelin up to 5.0
      micrograms/g in the control rice grains, indicating that exogenous Cd can be
      bound to glutelin up to this capacity. Simultaneous speciation of exogenous 113Cd
      and endogenous 111Cd was demonstrated to be highly effective for comparing the
      binding of Cd natural and artificial origins.

PMID- 9285887
TI  - Aluminum effect on lipid peroxidation and on the activities of superoxide
      dismutase and catalase in the cerebral hemisphere and liver of young chicks.
AB  - Aluminum was injected (i.p.) as aluminum sulphate (4, 40 and 100 mg/kg body
      weight, n = 5 per group) daily into day-old White Leghorn male chicks for 7, 15
      and 30 days. Aluminum (Al) treatment (100 mg dose) to chicks over 7 and 30 days
      resulted in a decrease in activities of cytosolic total and CN(-)-sensitive
      superoxide dismutase (SOD) in the cerebral hemisphere (CH). In the 15-day treated
      group, activities of cytosolic total, CN(-)-sensitive and CN(-)-insensitive SOD
      of CH were decreased in response to all doses of Al. In the liver, activities of
      cytosolic total and CN(-)-sensitive SOD were decreased in response to all doses
      of Al treatment for 7 and 15 days. But 40 and 100 mg doses were effective in
      decreasing activities of the enzymes in the 30-day treated group. The catalase
      (CAT) activity of CH of chicks was inhibited by all doses of Al under treatment
      for 7 days, but was inhibited only in the case of the 100 mg dose when the
      duration of treatment was increased to 15 days. The inhibition was again observed
      in chicks treated for 30 days in response to 40 and 100 mg doses. CAT activity of
      liver of chicks was decreased in response to all doses of Al in the 7-day treated
      group and in response to 40 and 100 mg doses in the 15- and 30-day treated
      groups. Al treatment did not affect lipid peroxide levels of CH and liver of
      chicks. These results suggest that decrease in activities in SOD and CAT in CH
      and liver of the chicks after Al treatment constitutes one of the factors for the
      mechanism of tissue injury by Al.

PMID- 9285888
TI  - Expression of selenoproteins in various rat and human tissues and cell lines.
AB  - Various rat and human tissues and cell lines naturally exposed to endogenous or
      exogenous oxidative stress were examined for their pattern of selenoprotein
      transcripts. Selenoprotein P mRNA was mainly expressed in rat kidney, testis,
      liver and lung. In testis, a high phospholipid hydroperoxide glutathione
      peroxidase (PHGPx) but only a weak cytosolic glutathione peroxidase (cGPx) signal
      was obtained. In kidney, spleen, heart, liver and lung cGPx mRNA levels were
      higher than those of PHGPx and for both only weak signals were obtained with
      brain mRNA. The Northern blot results concerning the tissue distribution of cGPx
      in the rat were fully supported by activity measurements. None of the human
      tissues revealed a PHGPx mRNA signal, whereas selenoprotein P transcripts were
      present in all human tissues with the highest abundance in heart, liver, and
      lung, tissues which also exhibited strong cGPx signals. The gastrointestinal
      glutathione peroxidase (GPx-GI) was only expressed in human liver and colon
      liver. Liver, the organ that showed the broadest repertoire of selenoproteins,
      has to cope with reactive oxygen intermediates produced during detoxification
      reactions. Human cell lines of the myeloic system that may be exposed to
      oxidative stress during inflammatory processes showed distinct cGPx signals:
      epithelial cells showed low cGPx signals. Similar cGPx mRNA levels were found in
      normal human thyroid tissue and thyroid carcinoma cells. Among the human cell
      lines selenoprotein P expression was detected in HepG2 and HTh74 thyroid cells.
      Our data confirm the necessity of getting specific information on distinct tissue
      and cell-specific patterns of selenoprotein expression as endpoints of selenium
      supply and biological function of the selenoprotein family. Analysis of total
      selenium contents of tissues or body fluids only provides integrative information
      on the global selenium status of individuals.

PMID- 9285889
TI  - Reference values for the trace elements copper, manganese, selenium, and zinc in
      the serum/plasma of children, adolescents, and adults.
AB  - Up to now few plasma or serum reference or serum reference values have been
      available for the assessment of the essential trace element supply status in
      different age groups covering the whole range of life range. In the present
      investigation, the concentrations of copper, manganese, selenium, and zinc were
      determined in the serum of 137 healthy children and in the plasma of 68 blood
      donors. The age distribution within these groups ranged from 1 month to 18 years
      and from 22 to 75 years. The determinations were carried out directly by means of
      electrothermal atomic absorption spectrophotometry with Zeeman background
      compensation. The adult plasma reference values (mean +/- 2 SD) were 1.65 +/- 8.6
      mumol/1 for copper, 14.3 +/- 11.4 nmol/1 for manganese, 0.80 +/- 0.36 mumol/1 for
      selenium, and 16.6 +/- mumol/1 for zinc. No correlation between concentration of
      elements and sex could be established. In the child and adolescent group, the
      manganese levels exhibited an age-dependent linear decrease (54% of the starting
      value, slope 0.92, r = 0.4, p < 0.001), the copper and the selenium
      concentrations, respectively, exhibited an exponential increase (107%, r = 0.59
      and 174%, r = 0.61), with the highest value in the age group of 6 to 10 years.
      Reference ranges are established for 9 different age groups. The results reflect
      the known physiological data on the trace element content in the tissue of
      children and their diet. The present study is an important pre-requisite for
      diagnosis and therapy of trace element deficiencies in all age groups.

PMID- 9285890
TI  - Liver and colon oxidant status in growing rats fed increasing levels of dietary
      iron.
AB  - A study with four groups, each with 9 individually-housed, male albino rats
      (clinical average weight = 65 g), was undertaken to examine the effect of
      increasing dietary iron levels on the oxidant status in liver and colon of
      growing rats. The basal maize/soya diet contained 70 mg iron per kg and was
      supplemented with 200 (group II), 500 (group III) and 2000 (group IV) mg Fe/kg
      from iron (II) fumarate. Liver-Fe was closely correlated (r = 0.997) with dietary
      Fe intake. Feeding diets supplemented with 500 and 2000 mg Fe/kg over 28 days
      resulted in significantly elevated TBA-RS in liver homogenates. Vitamin E in the
      liver was about 20% lower in group IV compared to the controls. Liver SOD, G6PDH
      and CAT activities were not influenced by dietary iron, whereas liver GSHPx was
      decreased in groups III and IV. TBA-RS in the colon mucosa significantly
      increased only at a dietary iron supply of 2000 mg per kg. Iron-enriched diets
      caused a moderate dose-dependent enhancement in the concentration of methane
      sulfinic acid in feces samples, which was formed by the reaction of hydroxyl
      radicals and dimethyl sulfoxide. Liver was more sensitive than the colon mucosa
      to iron-induced lipid peroxidation. Compared with the recommended iron
      requirements of growing rats very high dietary iron levels were necessary to
      induce oxidative stress.

PMID- 9285891
TI  - Influence of combined use of selenious acid and SH compounds in parenteral
      preparations.
AB  - The influence of the combined use of selenious acid and SH compounds (glutathione
      (GSH) and cysteine (Cys), or ascorbic acid (Asc)) on cultured venous vascular
      cells was investigated experimentally. When cultured human umbilical venous
      vascular endothelial cells were exposed to 10 microM of selenious acid combined
      with 0.5 mM-GSH or 0.5 mM-Cys, the release rates of [3H]-adenine and lactate
      dehydrogenase (LDH) from cells into the medium increased significantly as
      compared with after exposure to selenious acid alone, and damage to the vascular
      endothelial cells was found to be intensified. Addition of 1 microM of selenious
      acid simultaneously with 0.5 mM-GSH or 0.5 mM-Cys showed no differences in
      toxicity for the vascular endothelial cells as compared with the addition of
      selenious acid alone. On the other hand, simultaneous exposure to 10 microM of
      selenious acid and 1 mM-Asc induced no significant differences in the release
      rates of [3H]-adenine and LDH, and no damage was observed to the vascular
      endothelial cells. These results suggest that simultaneous addition of selenious
      acid together with GSH or Cys, which have the SH-group, may cause damage to the
      vascular endothelial cells. Therefore careful attention is warranted in total
      parenteral nutrition (TPN).

PMID- 9285892
TI  - Maltol complexes of vanadium (IV) and (V) regulate in vitro alkaline phosphatase
      activity and osteoblast-like cell growth.
AB  - Vanadium compounds have been found to possess insulin- and growth factor-mimetic
      effects. In consequence, these derivatives are potentially useful as effective
      oral therapeutic agents in diabetic patients. However, their use has been limited
      by various toxic side-effects and by the low solubility of different derivatives.
      Recently, vanadium complex with maltol, a sugar used as a common food additive,
      have been synthesised and investigated in animals, showing possible insulin
      mimetic effects with low toxic side-effects. In the present study we have
      investigated the effect of bis(maltolato)oxovanadium (IV) (BMOV) and
      bis(maltolato)dioxovanadium (V) (BMV) on bone cells in culture as well as their
      direct effect on alkaline phosphatase in vitro. A comparison was also made with
      the action of vanadate and vanadyl cation. Vanadium compounds regulated cell
      proliferation in a biphasic manner with similar potencies. Osteoblast
      differentiation, assessed by alkaline phosphatase activity, was found to be dose
      dependent, with the inhibitory effect being stronger for vanadate and BMOV than
      for vanadyl and BMV. All vanadium compounds directly inhibited bovine intestinal
      ALP with a similar potency. Thus, maltol vanadium derivatives behave in a similar
      way to vanadate and vanadyl in osteoblast-like UMR 106 cells in culture.

PMID- 9285893
TI  - Zinc and diarrhea in infants.
AB  - Due to dietary modifications including the intake of cereals, vegetables and the
      frequent use of soy milk instead of breast milk, children in developing countries
      with diarrhea frequently suffer from zinc deficiency. Furthermore, diarrhea leads
      to excess zinc losses. Beside low energy intake zinc deficiency contributes to
      continued diarrhea, which in turn accounts for half of the deaths from diarrhea
      in children. Zinc supplementation leads to accelerated regeneration of the
      mucosa, increased levels of brush-border enzymes, enhanced cellular immunity and
      higher levels of secretory antibodies. In addition, in stunted children zinc
      supplementation results in enhanced catch-up growth via higher levels of insulin
      like growth factor-I. Growth retardation is closely related to the risk of
      diarrheal diseases in children. These pathophysiological conclusions are
      supported by several controlled clinical traits which have provided evidence that
      zinc supplementation results in significant reduction in the risk of continued
      diarrhea. However, it remains to be clarified whether these benefits are
      attributable to pharmacological effects or if they can be related to the
      correction of an underlying deficiency state.

PMID- 9285894
TI  - Growth factors and diabetic nephrology: an overview.

PMID- 9285895
TI  - Involvement of transforming growth factor-beta and its receptors in the
      pathogenesis of diabetic nephrology.

PMID- 9285897
TI  - Monocyte chemotactic peptide-1 in diabetic nephropathy.

PMID- 9285896
TI  - Role of growth hormone, insulin-like growth factors (IGFs) and IGF-binding
      proteins in the renal complications of diabetes.
AB  - This review has updated recent facets of evidence for the significance of the
      GH/IGF system in the development of diabetic kidney disease. It seems evident,
      however, that there is still an extensive number of questions that need to be
      answered before diabetic kidney disease is fully understood. The knowledge we
      have today indicates that GH/IGF axis, through a complex system comprising GHR,
      GHBP, IGFs, IGF receptors and IGFBPs may be responsible for both early and late
      renal changes in experimental diabetes (Fig. 3). In view of the complexity of the
      GH/IGF system, it will be a challenge to fully characterize the renal effects of
      GH/IGFs in diabetic kidney disease. There is no doubt that information on this
      topic will occur with increasing pace in the near future and that a understanding
      of the above-mentioned mechanisms will allow the further development of existing
      antagonists and design of new drugs, which may prove to be useful for therapeutic
      manipulation in the treatment of diabetic nephropathy. The development of long
      acting somatostatin analogues and GH antagonists, both with a specific action on
      the GH/IGF axis, seems to be one important step ahead. The combined
      administration of one of these antagonists with other drugs with a well described
      renoprotective action (such as ACE inhibitors) opens an interesting new
      dimension.

PMID- 9285899
TI  - Insertion/deletion polymorphism in ACE gene as a predictor for progression of
      diabetic nephropathy.

PMID- 9285898
TI  - Alterations of intrarenal renin-angiotensin and nitric oxide systems in
      streptozotocin-induced diabetic rats.

PMID- 9285900
TI  - Atrial natriuretic peptide in diabetic nephropathy.

PMID- 9285901
TI  - Structure-function relationships in diabetic nephropathy: lessons and
      limitations.

PMID- 9285902
TI  - Nitric oxide in diabetic nephropathy.

PMID- 9285903
TI  - Role of glycated low density lipoprotein in mesangial extracellular matrix
      synthesis.

PMID- 9285904
TI  - Pathogenic role of advanced glycosylation end products in diabetic nephropathy.

PMID- 9285905
TI  - Activation of mitogen-activated protein kinase cascade in diabetic glomeruli and
      mesangial cells cultured under high glucose conditions.

PMID- 9285906
TI  - Protooncogene expression and diabetic kidney injury.

PMID- 9285907
TI  - Diabetic vascular dysfunctions: a model of excessive activation of protein kinase
      C.

PMID- 9285908
TI  - Gene transfer into the kidney: promises and limitations.

PMID- 9285909
TI  - Glucose transporters of the glomerulus and the implications for diabetic
      nephropathy.
AB  - Several glucose transporters have recently been identified in glomeruli, and in
      cultured glomerular cells. These include the facilitative glucose transporter
      isoforms GLUTs 1, 3 and 4, and sodium-glucose cotransport activity with
      characteristics of SGLT1. GLUTs 1, 3 and 4 are all high affinity, low capacity,
      facilitative glucose transporters which typically would be saturated at or near
      physiologic glucose concentrations. The SGLT transporter of mesangial cells is
      also a high affinity transporter which similarly could be saturated under normal
      glucose conditions. This suggests that in order for mesangial cells to take up
      excessive quantities of glucose in diabetes, changes in glucose transporter
      expression, translocation or activity may be required. Accordingly, recent
      investigations discovered positive-feedback regulation of the mesangial cell
      GLUT1 transporter by glucose, and a regulatory role for GLUT1 in glucose
      metabolism and extracellular matrix synthesis. Future investigations of glucose
      transporters in the pathogenesis of diabetic renal disease will now likely
      proceed in multiple directions, including but not limited to: (1) examination of
      their regulation by growth factors implicated in diabetic nephropathy, and the
      resultant effects on ECM synthesis; (2) determination of the mechanisms by which
      GLUT1 regulates the expression of aldose reductase, PKC, GLUT1, and other genes
      in the mesangial cell; and (3) Suppression of glucose transporters in attempts to
      prevent high glucose-induced diabetic glomerulosclerosis.

PMID- 9285910
TI  - Application of gene therapy to diabetic nephropathy.

PMID- 9285911
TI  - Acute oral toxicity of microcystin-LR, a cyanobacterial hepatotoxin, in mice.
AB  - Microcystin-LR (MCLR) is a hepatotoxic peptide produced by Microcystis
      aeruginosa, an alga found worldwide in reservoirs for drinking supply; however,
      acute oral toxicity of purified MCLR remains unknown. Therefore, a single dose of
      MCLR (more than 95% purity) ranging from 8.0 to 20.0 mg/kg body weight was orally
      given to female 6-week old BALB/c mice, and lethality and pathological changes
      were observed. Median lethal dose (LD50) of the orally given MCLR estimated by
      the up and down method was 10.9 mg/kg, which was 167 times higher than the i.p.
      LD50 value (65.4 microgram/kg by moving average method). Orally administrated
      toxin caused primarily hepatocellular injuries with characteristics of hemorrhage
      and necrosis. In situ end-labeling as well as electron microscopic observation
      revealed an induction of apoptotic cell death to hepatocytes. These results
      indicate the lethality of MCLR was much lower in oral dosage than by i.p.
      administration, but toxic effects are similar. In addition, apoptosis is
      considered one of major components in MCLR-induced hepatotoxicity.

PMID- 9285912
TI  - Isolation and characterisation of urushiol components from the Australian native
      cashew (Semecarpus australiensis).
AB  - Native cashew (Semecarpus australiensis) is a well-known food source for
      aboriginal people of northeastern Queensland and the Northern Territory. It is
      also well known that contact with the seeds at a certain stage of growth can
      cause sever dermatitis in susceptible individuals. To prepare the fruits for
      eating, they are commonly treated by leaching for 2-7 days with water followed by
      heating in bark, and this treatment apparently produces an edible cashew nut.
      Recently, attempts have been made to use this valuable source of food by a
      commercial company. It was necessary to identify the active principle(s) in the
      seeds to determine the most effective way of rendering the seed suitable for
      human consumption without altering the flavour. By using solvent extraction and
      silica-gel chromatography, a fraction containing one major urushiol was obtained.
      Its structure was confirmed by comparison of its NMR and mass spectral (MS) data
      with that previously reported. This compound, which is found in high yield, is
      also found in poison ivy (Toxiodenron radicans) and is responsible for dermatitis
      in susceptible individuals. A method of removing the active principle from the
      seed has been suggested.

PMID- 9285913
TI  - Seasonal variations in microcystin contents of Danish cyanobacteria.
AB  - One hundred ninety-eight of 296 phytoplankton net samples, collected from Danish
      fresh waters during 1993-1995, contained microcystins when analyzed by high
      performance liquid chromatography (HPLC), and the seasonal variations in
      microcystin contents were examined. Three genera, Anabaena, Microcystis, and
      Planktothrix, with microcystin-production potential were found. The highest
      percentage of the samples dominated by Anabaena and Microcystis was found in June
      July and July-November, respectively, and those by Planktothrix in May and
      October-November. The highest microcystin contents were found in samples
      collected in July and September. When pooling all samples by month of collection,
      no major differences in mean toxin contents were seen in samples collected from
      May through November, with the exception of slightly higher microcystin contents
      in September and October. The frequency of samples (all samples grouped by month
      of collection) with detected microcystins ranged from 62% in July (n = 116) to
      86% in May (n = 7). Variations in toxin profiles were found between 5 lakes
      sampled several times during 1993-1995, and in addition, quantitative and
      qualitative seasonal changes in microcystin content accompanied species
      composition changes in 3 of these lakes. Consistent blooms dominated by single
      species were characterized by more or less constant toxin profiles but variable
      toxin concentrations. Analysis of 6 samples from Lake Bryrup Langso 1995 by
      enzyme linked immunoabsorbent assay and HPLC revealed 1-70 and 0-737 micrograms
      microcystins/g dry wt, respectively. The discrepancy between the two detection
      methods may be attributed to the types of microcystin variants present,
      emphasizing the possible influence of seasonal variations in toxin profiles on
      the quantification of microcystins.

PMID- 9285914
TI  - Two new analogs of yessotoxin, homoyessotoxin and 45-hydroxyhomoyessotoxin,
      isolated from mussels of the Adriatic Sea.
AB  - Two new analogs of yessotoxin (YTX), homoYTX and 45-hydroxyhomoYTX, were isolated
      from the digestive glands of mussels cultured in the Adriatic coast of Italy.
      Their structures were determined by MS and NMR spectroscopies.

PMID- 9285916
TI  - Evaluation of chick embryo spinal motoneuron cultures for the study of
      neurotoxicity.
AB  - The objective of this study was to assess the performance of chick embryo
      motoneuron cultures for the study of neurotoxicants. The response of motoneurons
      to the cytotoxic effects of picrotoxin, strychnine, bulbocapnine, and the
      naturally occurring excitatory amino acids, N-methyl D-aspartate (NMDA) and L
      glutamate was studied by using a colorimetric viability assay using a vital dye.
      Selective cellular responses other than cell death were evaluated using a
      spectrofluorometric assay based on the response of an electrochromic styryl dye
      (Di-4-Anneps) to determine the expression of receptors for glycine, gamma
      aminobutyric acid (GABA), NMDA, and L-glutamate by motoneurons in culture. The
      performance of chick embryo motoneurons (E7) in culture was useful and
      informative in neurotoxicologic studies. Motoneurons (E7) were found to express
      receptors for glycine, GABA, NMDA, and dopamine. The presence of the receptors
      and the inherent characteristics of motoneurons to generate action potential at
      an early embryonic stage (E4) makes this culture system a reliable model to
      conduct mechanistic studies as well as for predictive screening tests for agents
      of pharmacologic and toxicologic potential.

PMID- 9285915
TI  - 30-day oral toxicity study of domoic acid in cynomolgus monkeys: lack of overt
      toxicity at doses approaching the acute toxic dose.
AB  - Domoic acid was orally administered to 3 cynomolgus monkeys at doses of 0.5 mg/kg
      for 15 days and then at 0.75 mg/kg for another 15 days. After the 30-day dosing
      period, the treated monkeys were killed. Parameters monitored as markers for
      toxicity included body weight, food and water consumption, clinical observations,
      hematology, serum chemistry, light microscopy of all major organs (including
      brain and retina), and glial fibrillary acid protein immunohistochemistry. Domoic
      acid in serum and 24-hour urine samples was measured at several time points. All
      parameters measured remained unremarkable. Domoic acid concentrations measured in
      the 24-hour urine samples indicated that gastrointestinal absorption in the
      monkey was approximately 4-7 percent of the administered dose, which is at least
      twice that previously reported for the rat.

PMID- 9285917
TI  - Effect of intraperitoneal infusion of deoxynivalenol on feed consumption and
      weight gain in the pig.
AB  - The mycotoxin deoxynivalenol (DON) is well documented to cause reduced feed
      consumption (FC) and weight gain (WG) rates in sensitive animal species. In the
      present study, the effect of DON on pigs when ingested as a DON-spiked diet was
      compared with toxin administered by a continuous-delivery osmotic pump that was
      implanted intraperitoneally (i.p.). The trial was conducted for a 7-day period.
      At 4 ppm dietary DON, overall FC and WG were reduced -14% and -8%, respectively,
      compared with control animals; at 9 ppm DON, values were -46% and -65% less,
      respectively. With i.p. infusion of te toxin, although FC was also reduced [-16%
      at 2 micrograms DON/hr (low dose) or -31% at 5 micrograms DON/hr (high dose)], WG
      rates were affected to a relatively less extent (-5% or -9%, respectively) than
      that noted with dietary DON. In pigs on dietary DON, both FC and WG were most
      affected during the initial 3-day period and showed significant recovery
      thereafter; however, in animals dosed by the i.p. pump, FC improved only
      moderately, and WG stayed relatively constant over the 7 days. The effect of
      dietary DON on WG appears to be influenced by more than just reduced feed intake,
      particularly at higher toxin concentrations.

PMID- 9285919
TI  - Substance abuse services for pregnant women: a medical approach.

PMID- 9285918
TI  - Absence of a synergistic effect between fumonisin B1 and N
      nitrosomethylbenzylamine in the induction of oesophageal papillomas in the rat.
AB  - Fumonisins and N-nitrosamines (NNO) are suggested risk factors in the development
      of human oesophageal cancer; exposure to both occurs in high risk populations in
      Africa and People's Republic of China. The hypothesis that the two would interact
      in oesophageal carcinogenesis was therefore tested by treating male rats with the
      known oesophageal carcinogen N-methylbenzylnitrosamine (NMBA), and fumonisin B1
      (FB1). The treatment groups were: Group 1, NMBA (2.5 mg/kg) intraperitoneally
      twice per week from week 2 to 4 inclusive; Group 2, as for group 1 but in
      addition FB1 (5 mg/kg) daily from weeks 1 to 5 inclusive by gavage; Group 3, FB1
      (5 mg/kg) alone daily from weeks 1 to 5 inclusive by gavage, and Group 4, vehicle
      treatment from week 1 to 5 inclusive. Two of 12 animals in group 1 developed
      oesophageal papillomas and a further two had oesophageal dysplasia. Data were
      similar in group 2, animals receiving both NMBA and FB1, with one of 12 animals
      having papillomas and three of 12 with dysplasia. Sphingolipid biosynthesis was
      affected in the kidney and slightly in the liver after fumonisin treatment but
      not in the oesophagus or lung as determined by sphinganine:sphingosine ratios in
      urine and tissues. These data show that there is no synergistic interaction
      between NMBA and FB1 in the rat oesophagus when the two compounds are
      administered together. It is nevertheless important to examine other experimental
      models and treatment protocols which may be more relevant to the human situation
      and also to pursue epidemiological investigations of the role of fumonisins in
      oesophageal cancer.

PMID- 9285920
TI  - Preembryo research: medical aspects and ethical considerations.
AB  - Recent advances in the field of reproduction have made it possible to obtain
      preembryos and to use them in many research applications. These include research
      into improving methods of IVF treatment, contraceptive research, preimplantation
      diagnosis, gene therapy, the study of malignant disease, and others. The
      benefits, academic and scientific, are enormous, but many moral and ethical
      issues and reservations exist. Potential sources from which the preembryos may
      originate may also lead to controversy. Pressure groups in various societies seek
      to hasten governments into legislation or other means of control. We conducted a
      MEDLINE search of all pertinent literature since 1980, and these findings have
      been reviewed.

PMID- 9285921
TI  - Platelet and hemorrhagic disorders associated with pregnancy: a review. Part I.
AB  - Disorders of coagulation remain an important potential cause of maternal
      morbidity and mortality. Bleeding disorders in pregnancy, unlike disorders of
      hypercoagulability, most often can have little impact on the mother but
      devastating consequences for the fetus. Further complicating the issue is that
      not all disorders of coagulation are inherited. Some are due to maternal
      illnesses unique to pregnancy, others are due to drug ingestion, and yet others
      remain idiopathic. In still other instances, thrombocytopenia is a minor
      consequence of a more severe disorder and will resolve when the inciting agent is
      removed or treated. A basic understanding of the pathophysiology of various
      conditions that lead to bleeding diathesis in pregnancy is necessary in order to
      effectively manage these varied clinical disorders. In addition, knowledge of
      whether the major morbidity is fetal or maternal or both can impact management.
      This review is concerned with the etiology, pathophysiology, diagnosis, and
      general management of commonly encountered disorders in pregnancy that place the
      mother and fetus at increased morbidity and mortality because of the potential
      for hemorrhage. Acutely acquired disorders and the resultant maternal
      manifestation versus a chronic disease process that is altered by the state of
      pregnancy are distinguished. Where possible, the incidence and prognosis of the
      disorder are provided. Actual cases are included to illustrate how similar
      presentations of distinctly different disorders can confuse and complicate an
      accurate diagnosis that is essential for appropriate management.

PMID- 9285922
TI  - Platelet and hemorrhagic disorders associated with pregnancy: a review. Part II.

PMID- 9285923
TI  - Intracellular degradation of C-peptides in molluscan neurons producing insulin
      related hormones.
AB  - Single Light Green Cells (LGC) of Lymnaea stagnalis, expressing four genes
      encoding insulin-related peptides (MIPs) and C-peptides, and sections from the
      median lip nerve (MLN) were subjected to MALDI-MS. Mass spectra of LGCs and MLNs
      were almost identical. Masses corresponding to those of the MIPs and some C alpha
      peptides could be distinguished. ProMIP III C alpha-peptide and C beta-peptides
      were not found. The spectra showed additional masses matching those of
      carboxyterminally truncated C alpha-peptides. Peptides with similar masses were
      isolated from MLN extracts by HPLC, using electrospray-MS screening. Amino acid
      sequence analysis revealed intact proMIP I, II and V C alpha-peptides and I, II C
      alpha-peptide 1-24, 1-22 and 1-15.

PMID- 9285924
TI  - Islet amyloid polypeptide in the gut and pancreas: localization, ontogeny and gut
      motility effects.
AB  - The occurrence of islet amyloid polypeptide (IAPP) in the gut and pancreas of
      several species and during ontogeny of the rat, was studied using
      immunocytochemistry. Effects of IAPP on rat ileal smooth muscle were assessed in
      vitro. Islets of most, but not all, species examined, displayed IAPP in insulin
      cells and, in some species, also in somatostatin- and peptide YY (PYY)-containing
      cells. In the gut, expression of IAPP varied among species; when present, IAPP
      was most abundant in the proximal part and co-localized with somatostatin, PYY,
      gastrin/cholecystokinin, enteroglucagon or serotonin. IAPP was first demonstrated
      at embryonic day 12 and 16 in islet and gastrointestinal endocrine cells,
      respectively. IAPP relaxed gut muscle and reduced electrical field stimulation
      evoked contractions, presumably by inhibiting acetylcholine release. Thus, IAPP
      expression in islets is consistent with an important role for IAPP in fuel
      metabolism; the gastrointestinal expression and motor effects of IAPP suggest
      that IAPP may modulate gastrointestinal function.

PMID- 9285926
TI  - Nociceptin, an endogenous ligand for the ORL1 receptor, has vasodilator activity
      in the hindquarters vascular bed of the rat.
AB  - The heptadecapeptide nociceptin, also known as Orphanin FQ, is a newly discovered
      endogenous ligand for the G-protein coupled, opioid-like receptor ORL1. In the
      present study, responses to intra-arterial injections of nociceptin were
      investigated in the hindquarters vascular bed of the rat. Under constant-flow
      conditions nociceptin induced dose-dependent decreases in hindquarters perfusion
      pressure when injected in doses of 1-30 nmol into the hindquarters perfusion
      circuit. The decreases in hindquarters perfusion pressure were rapid in onset and
      pressure returned to control values over a 3-6 min period. In terms of relative
      vasodilator activity, nociceptin was approximately equipotent to the nitric oxide
      donor, DEA/NO, and 30-fold less potent than adrenomedullin. These data
      demonstrate that nociceptin has significant vasodilator activity in the
      hindquarters vascular bed of the rat.

PMID- 9285925
TI  - Effect of enterostatin and kappa-opioids on macronutrient selection and
      consumption.
AB  - Enterostatin, the activation peptide of pancreatic procolipase, suppresses
      consumption of high-fat diets and selectively suppresses fat consumption over
      carbohydrate consumption. Kappa-opioid subtype agonists stimulate feeding whereas
      antagonists suppress feeding. We investigated the effects of enterostatin, the
      kappa-opioid agonist U50488, and the kappa-opioid antagonist nor-binaltorphimine
      (nor-BNI) on macronutrient selection and food consumption in rats adapted to
      choose between a high-fat (HF) diet or a low-fat-high-carbohydrate (LF) diet. In
      fasted rats, lateral cerebro-ventricular injection (LV) of enterostatin
      selectively suppressed consumption of the HF diet, with no effect on LF diet
      consumption. Nor-BNI also selectively suppressed consumption of the HF diet
      without affecting LF diet consumption. Additionally, U50488 prevented the
      suppression of consumption of the HF diet in response to enterostatin. In food
      sated rates, U50488 preferentially increased consumption of the HF diet and had
      no effect on consumption of the LF diet. Combined infusions of subthreshold doses
      of enterostatin and nor-BNI also inhibited consumption of the HF but not the LF
      diet, whereas combined infusions of maximal doses of enterostatin and nor-BNI had
      no additive effects. Collectively, these data suggest that a kappa-opioid pathway
      modulates selection and consumption of diets high in fat and that enterostatin
      modulates consumption of dietary fat by interacting with this pathway.

PMID- 9285927
TI  - Effect of 7-nitroindazole on tolerance to morphine, U-50,488H and [D-Pen2, D
      Pen5] enkephalin in mice.
AB  - The effects of 7-nitroindazole (7-NI), an inhibitor of the neuronal nitric oxide
      synthase (nNOS) which does not increase blood pressure, on tolerance to the
      antinociceptive activity of mu-(morphine), kappa-(U-50,488H) and delta-([D-Pen2,
      D-Pen5]enkephalin, DPDPE) opioid receptor agonists were determined in mice. Male
      Swiss-Webster mice were made tolerant by twice daily injections of morphine (20
      mg/kg, s.c.), U-50,488H (25 mg/kg, i.p.) or DPDPE (20 micrograms/mouse, i.c.v.)
      for 4 days. When tested on day 5, tolerance to their antinociceptive activity was
      evidenced by decreased response in chronic drug treated mice in comparison to
      vehicle-injected mice. Concurrent administration of 7-NI (20, 40 or 80 mg/kg,
      i.p.) with DPDPE did not modify the development of tolerance to the
      antinociceptive action of DPDPE. However, 7-NI (40 or 80 mg/kg, i.p.) inhibited
      the development of tolerance to the antinociceptive activity of morphine and U
      50,488H but the lower dose of 7-NI (20 mg/kg, i.p.) was not effective. Chronic
      administration of 7-NI by itself did not modify the acute response to morphine, U
      50,488H or DPDPE. It is concluded that a specific inhibitor of nNOS can inhibit
      tolerance to the antinociceptive activity of mu- and kappa- but not of delta
      opioid receptor agonists in mice.

PMID- 9285928
TI  - Tissue-specific regulation of fat cell lipolysis by NPY in 6-OHDA-treated rats.
AB  - The effects of neuropeptide Y (NPY), peptide YY (PYY), [Leu31, Pro34]NPY, and NPY
      (13-36) on adipocyte lipolysis have been studied in subcutaneous (inguinal) and
      visceral (parametrial) rat adipose tissues. A 48-h fasting period and chemical
      sympathectomy were used to evaluate the regulation of Y1 and Y2 pathways in rat
      adipocytes. NPY, PYY, and [Leu31, Pro34]NPY significantly inhibited fat cell
      lipolysis by about 25% in both tissues (p < or = 0.05). This inhibition was
      achieved mainly through the Y1 pathway. No significant response to NPY (13-36)
      was observed, suggesting a lack of involvement of the Y2 pathway in the
      antilipolytic effect of NPY and PYY. The 48-h fasting period led to the loss of
      the Y1 inhibitory effect previously observed in control rats. On the other hand,
      the chemical sympathectomy induced a 35% increase of fat cell lipolysis (p < or =
      0.05). The latter involved the Y2 pathway as stimulated by NPY (13-36), and was
      observed in the parametrial tissue exclusively. These results suggest that: a)
      rat Y receptors reported to exhibit Gi responses can also express Gs-like
      responses, and b) visceral and subcutaneous adipose tissues exhibit specific
      regulation of fat cell lipolysis.

PMID- 9285929
TI  - Regional vascular and cardiac responses to systemic neuropeptide-Y in normal and
      diabetic rats.
AB  - Diabetes is associated with altered autonomic activity, and both the peripheral
      and central nervous content of NPY is altered in diabetes suggesting that part of
      the cardiovascular dysfunction of diabetes may be associated with altered
      responses to NPY. We evaluated the mean arterial pressure (MAP), heart rate (HR)
      and regional blood flow (BF) in response to NPY in normal and diabetic rats. Male
      Wistar rats were made diabetic using streptozotocin and maintained without
      insulin treatment for 28-30 days. Normal and diabetic animals were anesthetized,
      the femoral artery cannulated, and flow probes placed around the iliac, renal and
      superior mesenteric arteries. Dose dependent responses to NPY infusion were
      determined for MAP, HR and BF. Conductance was calculated from BF/MAP. In normal
      rats NPY increased the MAP in a dose-dependent fashion but did not alter the HR.
      NPY decreased the BF in the iliac artery in a dose-dependent fashion while the
      renal BF was decreased only at the highest dose, and the superior mesenteric BF
      was not affected. The conductances in all vascular beds were decreased dose
      dependently. NPY in diabetic rats also increased MAP and did not affect HR. In
      diabetic rats NPY also decreased BF in iliac and renal arteries but contrastingly
      increased BF in the superior mesenteric artery. Again conductances in all three
      vascular beds were decreased by NPY. When comparing diabetic response to NPY to
      normals we noted that the MAP response was less in the diabetic, but the HR and
      regional BF were not different. The vascular conductances in response to NPY were
      attenuated in the diabetic vessels especially the iliac and superior mesenteric.
      We conclude that systemic NPY increases MAP as a result of decreased vascular
      conductance and this vasopressive effect of NPY is diminished in diabetics.

PMID- 9285930
TI  - Goldfish gamma-preprotachykinin mRNA encodes the neuropeptides substance P,
      carassin, and neurokinin A.
AB  - Two cDNAs, size 969 bp and 1146 bp respectively, encoding goldfish gamma
      preprotachykinin (gamma-PPT) were identified. Both cDNAs contain the same 345 bp
      open reading frame. The deduced 114-amino acid gamma-PPT contains the sequence of
      substance P, carassin and neurokinin A. sequence analysis of the two cDNA 5'
      untranslated regions shows that the two cDNAs may represent different PPT-A gene
      transcripts resulting from the alternative transcriptional start sites.
      Expression of gamma-PPT mRNA was detected in a wide range of brain areas from the
      olfactory bulbs to the posterior brain region, as well as in the intestine,
      testis and pituitary.

PMID- 9285931
TI  - Further evidence that the tachykinin PG-KII is a potent agonist at central NK-3,
      but not NK-1, receptors.
AB  - Intracerebroventricular (i.c.v.) injection of tachykinins (TKs) inhibits ethanol
      intake and angiotensin II-induced water intake; the effects are apparently
      mediated by NK-3 and NK-1 receptors, respectively. The present study evaluated
      the effect of the TK PG-KII, a novel kassinin-like peptide isolated from the skin
      of the Australian frog Pseudophryne guntheri, in these in vivo tests for central
      activity. PG-KII, given by i.c.v. injection, potently inhibited alcohol intake in
      genetically selected alcohol-preferring rats, being about 3 times more potent
      than the selective NK-3 receptor agonist NH2-SENK. The dose of 100 ng/rat, that
      markedly inhibited ethanol intake, did not inhibit food intake and prandial
      drinking in food deprived rats, providing evidence that the effect of PG-KII on
      ethanol intake is behaviorally selective. The effect on ethanol intake was
      inhibited by i.c.v. injection of the NK-3 receptor antagonist R820, but was not
      modified by the NK-1 receptor antagonist SR 140333. PG-KII inhibited drinking
      induced by angiotensin II only at doses of 300 or 1000 ng/rat, being about 5
      times less potent than the selective NK-1 receptor agonist [Sar9, Met(O2)11]
      substance P. These doses of PG-KII produced also marked increase in competing
      behaviors, such as grooming and locomotion. The dose of 1000 ng/rat evoked a
      general inhibition of the ingestive behavior, reducing also food intake. The
      i.c.v. injection of the NK-1 receptor antagonist SR 140,333 only slightly
      inhibited the effect of PG-KII on angiotensin II-induced drinking, while it
      markedly reduced that of [Sar9, Met(O2)11] substance P. These findings, in
      accordance with those of previous studies, indicate that PG-KII is endowed with
      marked activity at central NK-3 receptors, and low activity at NK-1 receptors.

PMID- 9285932
TI  - Retinoic acid regulation of the VIP and PACAP autocrine ligand and receptor
      system in human neuroblastoma cell lines.
AB  - Neuroendocrine tumors, neuroblastoma in particular, commonly express the
      neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase
      activating peptide (PACAP) and their receptors. Retinoic acid (RA) has been shown
      to induce differentiation of neuroblastoma cell lines, possibly by augmenting or
      interfering with neuropeptide autocrine loops. We sought to determine which
      receptor gene subtypes are expressed in selected human neuroblastoma cell lines
      (SH-SY5Y, IMR-32, and LA-N-5), and the effect of RA on the VIP/PACAP
      ligand/receptor system. Expression of both PACAP1 and VIP1/PACAP2 receptor genes
      was detected by Northern analysis, which characteristically encode Type I (PACAP
      preferring), and Type II (bivalent VIP/PACAP) receptors, respectively. Binding
      experiments carried out on IMR-32 cells, using 125I VIP and 125I PACAP-27 as
      tracers, corroborated that both receptor subtypes were expressed. In contrast to
      RA upregulation of VIP binding (confirmed here in IMR-32 cells), levels of both
      receptor mRNAs were reduced after RA treatment. VIP mRNA in each cell line was
      increased by RA, whereas PACAP mRNA, detected in IMR-32 cells only, was reduced.
      The studies indicate that several components of the VIP/PACAP autocrine system
      are regulated in neuroblastoma cell lines during RA differentiation.

PMID- 9285933
TI  - Functional type II VIP-PACAP receptors in human airway epithelial-like cells.
AB  - VIP-PACAP receptors were characterized in a human airway epithelial-like cell
      line (Calu-3), Pituitary adenylate cyclase activating polypeptide (PACAP) 1-27,
      PACAP 1-38, vasoactive intestinal polypeptide (VIP) and the beta 1- and beta 2
      adrenoceptor agonist isoproterenol (3 nM-1 microM) increased cAMP concentration
      dependently. The peptides and isoproterenol displayed similar potencies (range of
      means pEC50[M]: 6.5-7.1). The maximum increase in cAMP (Emax in % of basal cAMP
      level) was similar for the peptides (range of means Emax: 2500-5100%).
      Pretreatment with the peptidase inhibitors captopril (10 microM) and
      phosphoramidon (1 microM) significantly increased the cAMP response to PACAP 1-38
      (to 480% of control) only.

PMID- 9285934
TI  - Conversion of angiotensin I to angiotensin II by chymase activity in human
      pulmonary membranes.
AB  - An aprotinin-insensitive, angiotensin II (Ang II)-forming chymase has recently
      been identified in human heart tissue. We studied the hydrolysis of Ang I in
      human lung membranes. The hydrolysis products Ang II, Ang III, Ang-(1-9), Ang-(2
      9), Ang-(1-7) and Ang-(8-10) appeared in membrane preparations from four
      patients. Two metabolic pathways for the formation of Ang II were identified; one
      depending on ACE activity (1.4 nmol Ang II/min/mg membrane protein) and the other
      on serine protease activity (2.1 nmol/min/mg). The serine protease activity was
      inhibitable to only 30 +/- 8% (mean +/- SEM) by aprotinin, suggesting chymase
      activity to play a role in the Ang I-conversion of human lung.

PMID- 9285935
TI  - Effect of ETA receptor antagonists on cardiovascular responses induced by
      centrally administered sarafotoxin 6b: role of sympathetic nervous system.
AB  - The present study was carried out to investigate the cardiovascular effects of
      centrally administered SRT6b in saline, BQ123 and BMS182874 pretreated male
      Sprague-Dawley rats, using a radioactive microsphere technique. SRT6b (100 ng,
      ICV) produced a transient increase (40%) in blood pressure at 5 min followed by a
      sustained decrease (-42%) at 30 and 60 min in control rats. Total peripheral
      resistance and heart rate were not significantly altered. Cardiac output
      increased (16%) at 5 min and decreased 30 and 60 min following SRT6b
      administration. Central venous pressure was not affected by SRT6b. Regional blood
      flow and vascular resistance did not change at 5 min following administration of
      SRT6b. However, a significant decrease in blood flow to the brain, heart,
      kidneys, liver, spleen, gastrointestinal tract and mesentery and pancreas was
      observed 30 and 60 min following administration of SRT6b in control (saline
      treated) rats. Pretreatment with ETA selective receptor antagonists, BQ123 (10
      micrograms, ICV) or BMS182874 (50 micrograms, ICV) significantly attenuated the
      pressor and depressor effects of centrally administered SRT6b. SRT6b induced
      decrease in blood flow was completely blocked by pretreatment with BQ123 or
      BMS182874. ET-1 (100 ng, ICV) produced an increase followed by a decrease similar
      to SRT6b. Reserpine (5 mg/kg, IP) pretreatment attenuated the cardiovascular
      effects of ET-1. Role of sympathetic nervous system was determined by measuring
      splanchnic nerve activity. SRT6b when administered in the lateral cerebral
      ventricle did not produce any significant effect at 5 min, however, a significant
      decrease in sympathetic nerve activity was observed 30 min after its
      administration. It is concluded that centrally administered SRT6b produces
      significant changes in systematic and regional blood circulation which can be
      completely blocked by ETA receptor antagonist. The cardiovascular effects of
      centrally administered SRT6b appear to be mediated through the sympathetic
      nervous system.

PMID- 9285936
TI  - Full and partial agonist activity of C-terminal cholecystokinin peptides at the
      cloned human CCK-A receptor expressed in Chinese hamster ovary cells.
AB  - The agonist activities of the C-terminal cholecystokinin peptides sulfated
      cholecystokinin octapeptide (CCK-8S), non-sulfated cholecystokinin octapeptide
      (CCK-8NS), pentagastrin and CCK-4 at the cloned human CCK-A receptor expressed in
      Chinese hamster ovary cells were evaluated in two functional assays of receptor
      activation. [125I]-CCK-8S displacement studies employing membranes derived from
      these cells revealed the expected rank order of affinity for a number of CCK
      receptor ligands. CCK-8S was a potent agonist in (i) stimulating the mobilization
      of intracellular free Ca2+, measured with the Ca2+ sensitive fluorescent
      indicator FURA-2, and (ii) stimulating increases in extracellular acidification
      rates, measured by microphysiometry. Consistent with their lower affinities for
      CCK-A receptors, CCK-8NS, pentagastrin and CCK-4 were weaker agonists in both
      functional assays. In addition, these peptides exhibited partial agonist activity
      relative to the maximum response observed with CCK-8S in both assays. These
      results demonstrate that CCK-8S represents the minimum ligand requirement for
      both high affinity and full agonist activity at the human CCK-A receptor subtype.

PMID- 9285937
TI  - Development of a sensitive and specific assay system for cholecystokinin
      tetrapeptide.
AB  - Cholecystokinin is a gastrointestinal and neuropeptide which has been implicated
      in a wide range of physiological and behavioral processes. We have developed a
      sensitive and specific assay system to measure the various forms of
      cholecystokinin (CCK) in human plasma. This 3-step system involves i) extraction
      of CCK fragments from plasma using reverse phase chromatography; ii) separation
      of peptides by high performance liquid chromatography; and iii) detection and
      quantification of peptides with a double-antibody radioimmunoassay, using an
      antibody raised against cholecystokinin tetrapeptide (CCK-4) coupled to
      thyroglobulin and 125I Bolton-Hunter CCK-4 as tracer. The antibody detects CCK-4,
      sulfated CCK-8 (CCK-8S) and nonsulfated CCK-8 (CCK-8ns) with equal affinity. The
      lower limit of detection is 2.7 fmol, with an ED50 of 10.6 +/- 2.2 fmol. Mean CCK
      like immunoreactivity (CCK-LI) in the plasma of 12 healthy subjects was
      determined to be 12.9 +/- 2.1 pM CCK-4 equivalents. Concentrations of each
      individual peptide in plasma were determined to be 1.0 +/- 0.2 pM, 3.4 +/- 0.8 pM
      and 1.9 +/- 0.4 pM for CCK-4, CCK-8s and CCK-8ns respectively.

PMID- 9285938
TI  - Activation of Na+ channels in GH3 cells and human pituitary adenoma cells by
      PACAP.
AB  - The effects of pituitary adenylate cyclase activating polypeptide (PACAP) on ion
      channels were examined in GH3 cells human pituitary adenoma cells. In GH3 cells,
      PACAP-38 (10-9 M) reversibly activated tetrodotoxin-sensitive NA+ channels but
      had little effect on nicardipine-sensitive Ca2+ channels. PACAP-induced increase
      in Na+ currents was inhibited by PACAP (6-38), a specific PACAP receptor
      antagonist, and Rp-cAMPs, an inhibitor for protein kinase A, and mimicked by 8
      bromo-cAMP. In human pituitary adenoma cells, PACAP also activated tetrodotoxin
      sensitive Na+ channels and growth hormone secretion. These results suggest the
      possibility that PACAP can activate voltage-gated Na+ channels via adenylate
      cyclase-protein kinase A pathway in the pituitary.

PMID- 9285939
TI  - Effects of GHRP-2 and hexarelin, two synthetic GH-releasing peptides, on GH,
      prolactin, ACTH and cortisol levels in man. Comparison with the effects of GHRH,
      TRH and hCRH.
AB  - GHRP-2 (D-Ala-D-beta Nal-Trp-D-Phe-Lys-NH2) and Hexarelin (HEX) (His-D-2
      methylTrp-Ala-Trp-DPhe-Lys-NH2) are synthetic, non-natural super-analogs of GHRP
      6 endowed with potent stimulatory effect on GH secretion and slight stimulatory
      effect on PRL, ACTH and cortisol levels. Their GH-releasing activity ahs never
      been compared each other and their effects on PRL, ACTH and cortisol have never
      been compared with that of other stimuli. To clarify these points, in 6 normal
      young adults (22-27 yr) we studied the GH, PRL, ACTH and cortisol responses to 1
      and 2 micrograms/kg i.v. GHRP-2 and HEX comparing them with that after 1
      micrograms/kg i.v. GHRH and 400 micrograms i.v. TRH + 2 micrograms/kg i.v. hCRH.
      The Gh responses to 2 micrograms/kg i.v. GHRP-2 or HEX, compared with those to 1
      microgram/kg GHRH, were also studied in 6 normal elderly subjects (66-73 yr). In
      young adults 1 microgram/kg i.v. GHRP-2 and HEX induced a similar, strong GH
      response, which was higher (p < 0.05) than that to GHRH. The administration of
      2.0 micrograms/kg i.v. GHRP-2 and HEX again elicited a similar GH response, which
      was higher (p < 0.05) than that after the 1.0 microgram/kg dose. In elderly
      subjects, the GH those in young subjects. In young adults, the PRL responses to
      all doses of GHRP-2 or HEX were similar and lower (p < 0.01) responses were
      similar to those to hCRH. In conclusion, our results demonstrate that, in man,
      GHRP-2 and HEX have similar, 2 and HEX is not fully specific, as they induce
      similar increases in PRL, ACTH and cortisol levels. The PRL-releasing activity of
      GHRPs is lower than that of TRH while their ACTH/cortisol-releasing activity is
      similar to that of hCRH.

PMID- 9285940
TI  - The protective effect of 5-HT3 receptor antagonist in thyrotropin releasing
      hormone-induced gastric lesions.
AB  - The present study examined 1) oxidative stress and gastric lesions induced by
      thyrotropin releasing hormone (TRH) 2) The effect of a 5-hydroxytryptamine3 (5
      HT3) receptor antagonist, ICS 205930 on protective effect of calcitonin on
      gastric lesions produced by TRH. Calcitonin (5 micrograms/10 microliter) was
      injected i.c.v. 10 min before TRH (10 micrograms/10 microliter, i.c.v.) injection
      or ICS 0.5 mg/kg, (i.p.) was given 60 min prior to calcitonin or TRH to rats.
      Ulcer index, lipid peroxidation (LP) and glutathione (GSH) levels were quantified
      3 h after TRH injection in the stomach, liver and brain. TRH caused mucosal
      lesions (UI: 10.0 +/- 2.0 mm) without changing gastric GSH and LP. JCS did not
      alter the protective effect of calcitonin against TRH-induced lesions but
      attenuated. TRH-induced lesion formation. The oxidative effects of calcitonin or
      ICS were similar to TRH but both drugs attenuated gastric lesion formation.
      Hence, oxidative changes in tissues studied are not directly involved in TRH
      induced lesions.

PMID- 9285941
TI  - Interaction of fibronectin with integrin receptors: evidence by use of synthetic
      peptides.

PMID- 9285943
TI  - The effect of vasoactive intestinal peptide (VIP) on the testicular tissue
      histamine level of immobilized + cold stressed rats.
AB  - The effects of VIP on testicular tissue histamine level of stressed
      (immobilization and cold) rats were investigated. Sixteen Sprague-Dawley adult
      male rats were used and divided into three groups. Testicular tissue histamine
      was measured by HPLC. Stress caused a significant increase in the testicular
      tissue histamine level. VIP treatment decreased histamine to baseline.

PMID- 9285942
TI  - Actions of FMRFamide-related peptides on the gCa2+ of the C1 neuron in Helix
      aspersa.
AB  - The endogenous neuropeptides FMRFamide and FLRFamide (tetrapeptides) reversibly
      reduced a voltage-activated calcium current in the C1 neuron of Helix aspersa by
      an average of 20%. Two structurally related heptapeptides, pQDPFLRFamide and
      pQDPFLRIamide, both derived from another precursor protein in this species, did
      not reduce the current at all.

PMID- 9285944
TI  - Association of autoimmune thyroid disease with a microsatellite marker for the
      thyrotropin receptor gene and CTLA-4 in a Japanese population.
AB  - To examine the genetic contribution of the thyroid-stimulating hormone receptor
      (TSHR, or thyrotropin receptor) gene to autoimmune thyroid disease (AITD), we
      identified a dinucleotide repeat polymorphism near the TSHR gene that mapped to
      an 8.6 cM interval between D14S74 and D14S55 on the long arm of human chromosome
      14. Association studies revealed a significant difference (p = 3.8 x 10(-5)
      between the TSHR microsatellite allele frequency distribution in 81 unrelated
      Japanese AITD patients and 113 Japanese controls, with a significant increase in
      the 180 pb allele (allele 1) of the microsatellite sequence (p = 5.8 x 10(-7).
      The risk for AITD with the 180 bp allele was 3.5, with association highly
      significant in female patients (p = 1.1 x 10(-5) and less dramatic, but still
      significant, in male patients (p = .02). These results suggest that the 180 bp
      allele of the TSHR microsatellite is associated with a susceptibility locus for
      AITD in Japanese patients. Two additional genetic markers have been evaluated for
      association in the Japanese AITD patients. The TSHR codon 52 (C52-->A52)
      transition mutation was not observed in the Japanese. A polymorphism for the CTLA
      4 gene was genotyped and, while association with AITD was not observed (p = .15),
      a significant association was observed between CTLA-4 alleles of 110 bp (p = .01)
      and 106 bp (p = .004) and susceptibility to primary hypothyroidism or idiopathic
      myxedema, respectively.

PMID- 9285945
TI  - Autoantibodies in pernicious anemia type I patients recognize sequence 251-256 in
      human intrinsic factor.
AB  - Pernicious anemia is an organ-specific autoimmune disease characterized by
      cobalamin deficiency, megaloblastic anemia, neuropathy, and autoimmune gastritis
      with anti-intrinsic factor autoantibodies. Type 1 anti-intrinsic factor
      autoantibodies block the cobalamin binding site of the intrinsic factor, a
      gastric protein required for the assimilation of cobalamin. The aim of our study
      was to identify the epitope domain of type 1 antibodies. Different series of
      peptides derived from the intrinsic factor sequence were synthesized and tested
      for antibody binding in enzyme-linked immunosorbent assay, radioisotope assay,
      gel filtration, and SDS-PAGE autoradiography. One of these peptides, named IF-R7
      (the intrinsic factor aminoacid sequence 251-265), showed a type 1 antibody
      binding activity and inhibited, in vitro, their blocking activity with Ki at 2.3
      microM. The cross-linking of IF-R7 to beta-lactoglobulin produced type 1 anti
      intrinsic factor antibodies in immunized sheep. In vivo Schilling tests performed
      on guinea pigs also revealed IF-R7 peptide inhibition of type 1 antibody blocking
      activity. 256Ser, 258Lys, 262Tyr and 265Val of the IF-R7 were essential for the
      epitope recognition. Reactivity with type 1 antibodies was found in IF-R7
      homologous peptides from herpesvirus Saimiri and from pathogenic Escherichia
      coli. In conclusion, the epitope of type 1 anti-intrinsic factor autoantibodies
      is located in the 251-265 amino acid sequence of the protein. The identification
      of this epitope will enable the definition of an experimental animal model of
      anti-IF autoimmunity in order to study the pathogenesis of pernicious anemia.

PMID- 9285946
TI  - Insulin stimulates rat calmodulin I gene transcription through activation of Sp1.
AB  - We have shown previously that insulin positively regulates transcription of the
      rat calmodulin (CaM) I gene. This activation occurs concomitantly with the
      activation of the low-Km adenosine 3':5'-cyclic phosphate phosphodiesterase
      (PDE), which appears to be coregulated with CaM. Rat hepatoma H-411E cells were
      transfected with plasmids containing various lengths of the putative CaM promoter
      coupled to a luciferease reporter and were challenged with insulin. We
      demonstrate that insulin-stimulated transcription of CaM I gene is mediated by a
      392-bp 5'-flanking region of the CaM I gene, encompassing 185 bp downstream and
      207 bp upstream of the start site of transcription. The CaM I promoter contains
      three potential Sp1 sites, located at -114 through -109 [(3), +], -77 through -72
      [(2), -] and at +53 through +58 [(1), +]. The gel mobility shift assays
      demonstrated that nuclear protein(s) associate with all three sp1 sites. We
      present data demonstrating the relative importance of the three Sp1 sites for the
      insulin effect: prCaM I 1835, 3.8x, delta 1081; prCaM I 392, 5.3x, delta 1055;
      prCaM I 180, 3.7x, delta 462; prCaM I 237, 1.6x, delta 478; prCaM I 139, 2.6x,
      delta 182; prCaM I 130, 2.1x, delta 194; and prCaM I 1463, negligible activity.
      In summary, the maximal insulin stimulation of CaM gene expression is seen when
      the promoter region contains at least two Sp1 sites.

PMID- 9285947
TI  - Segregation of Allgrove (triple-A) syndrome in Puerto Rican kindreds with
      chromosome 12 (12q13) polymorphic markers.
AB  - Allgrove syndrome (AS), also known as triple-A syndrome, is a rare cause of
      congenital adrenal insufficiency due to adrenocorticotropic hormone resistance.
      It is inherited in an autosomal recessive manner and is associated with
      achalasia, alacrima, and other neurological abnormalities, including autonomic,
      sensory, and upper- and lower-motor neuropathy, deafness, and mental retardation.
      Although the etiology of AS remains unknown, recently the disease was linked to a
      chromosome 12 locus (corresponding cytogenetic band 12q13) in consanguineous
      families of European ancestry. In the present study, we investigated four
      nonconsanguineous families with documented inheritance of AS for linkage with the
      reported 12q13 locus. Eighteen subjects were studied, of whom five were affected
      by AS. DNA was extracted from peripheral blood lymphocytes and amplified by
      standard methods with primers from polymorphic sequence tagged sites (STSs)
      located in the chromosome 12q13 region. Two-point logarithm-of-odds (LOD) score
      analysis revealed a maximum LOD score of 1.7 for STSs D12S361 and D12S368 without
      any recombinants [recombination distance (theta) = 0]. Multipoint linkage
      analysis defined an area of estimated genetic distance less than 0.5 cM
      (approximately 500,000 bp) between STSs D12S361 and D12S359 that is most likely
      to contain the AS gene(s). We conclude that, in Puerto Rican families, AS
      segregates with polymorphic markers that have been mapped to the chromosome 12q13
      locus, revealing the absence of heterogeneity for this syndrome in a genetically
      distinct population. Candidate genes in the region include those that code for
      several of the keratin proteins, transcription factors, and others.

PMID- 9285948
TI  - Presentation of the 1997 George M. Kober Medal to Helen Ranney.

PMID- 9285950
TI  - George M. Cober Lecturer: Mark T. Keating. Molecular basis of the long-QT
      syndrome associated with deafness.
AB  - Jervell and Lange-Nielsen syndrome is an autosomal recessive form of long-QT
      syndrome. In addition to QT interval prolongation, this disorder is associated
      with congenital deafness. Jervell and Lange-Nielsen syndrome is rare, but
      affected individuals are susceptible to cardiac arrhythmias with a high incidence
      of sudden death and short life expectancy. A proband with Jervell and Lange
      Nielsen syndrome and family members were ascertained and phenotypically
      characterized. Linkage, mutational, and DNA sequence analyses were used to define
      the genetic basis of this disorder. We found that the proband had long-QT
      syndrome and sensory deafness. Some family members also had QTc prolongation with
      an autosomal dominant pattern of inheritance, but these patients had normal
      hearing. The gene responsible for QTc prolongation in this family was mapped to
      chromosome 11p15.5 using linkage analyses. The maximum LOD score at D11S1318 was
      5.46, indicating odds greater than 100,000:1 favoring linkage. Mutation analyses
      revealed a single base pair insertion in KVLQT11, the potassium channel gene
      responsible for chromosome 11-linked long-QT syndrome. This mutation caused a
      premature stop codon. All family members with QTc prolongation, except the
      proband, were heterozygous for the mutation. The proband with Jervell and Lange
      Nielsen syndrome resulted from a consanguineous marriage and was homozygous for
      the KVLQT1 mutation. Homozygous mutation of KVLQT1 causes Jervell and Lange
      Nielsen syndrome. Members of Jervell and Lange-Nielsen syndrome families should
      be examined for long-QT syndrome, even if they have normal hearing.

PMID- 9285951
TI  - The population of users of upper limb prostheses attending the Oxford Limb
      Fitting Service.
AB  - There is no central database that records the changing provision of prostheses in
      the United Kingdom. Experience suggests there have been some shifts in the
      population, particularly in the past decade. Because the detailed records of
      these changes are contained in the patients' medical records it is difficult to
      assess the substance of these data except on an individual basis; the larger
      picture the sifting of a centre's or many centres' data. This paper describes the
      analysis of one such set of records at the Oxford Limb Fitting Centre. It relates
      the profile of the population that attends the centre to the general population,
      and compares the information with that obtainable from other sources. The
      possible causes for the findings are discussed.

PMID- 9285952
TI  - Epidemiology of lower limb amputees in the north of The Netherlands: aetiology,
      discharge destination and prosthetic use.
AB  - The aim of this study was to give a retrospective review of all lower limb
      amputations performed in the 3 northern provinces of the Netherlands in 1991
      1992. Assembled data were compared with the existing information in the National
      Medical Register (NMR) over the same period. With the participation of all
      regional hospitals, 473 lower limb amputations from transpelvic to
      transmetatarsal level were identified. Of the amputations 94% were performed for
      vascular pathology, 3% for trauma, and 3% for oncologic reasons. After surgery a
      prosthesis was provided to 48% of the amputees. The actual number of performed
      amputations exceeds the number of amputations registered by the NMR by 9%.
      Incidence rates of lower limb amputations in the Netherlands are 18-20/100,000
      over the last 12 years. These numbers are lower than in other areas and no sharp
      decrease in frequency compared with other countries in Western Europe.

PMID- 9285953
TI  - Static versus dynamic prosthetic weight bearing in elderly trans-tibial amputees.
AB  - The purpose of this study was to compare prosthetic weight-bearing tolerance in
      the standing position to the dynamic vertical ground reaction forces (VGRF)
      experienced during walking in elderly dysvascular trans-tibial amputees. Ten
      unilateral trans-tibial amputees attending an amputee clinic (mean age = 67 +/-
      6.5 years) were selected as subjects. Selection criteria were the level of
      amputation, age, medical fitness to participate and informed consent. Each
      participant completed five trials of standing (static) weight bearing measurement
      followed by 10 walking (dynamic) trials on a 10m level walkway, five trials for
      each limb, Static weight bearing (SWB) was measured using standard bathroom
      scales. Dynamic weight bearing (DWB) was measured during gait using a Kistler
      multichannel force platform. T-tests for dependent means indicated that the
      forces borne in prosthetic single limb stance (mean = 0.97 +/- 0.03 times body
      weight (BW)) were significantly lower than the forces borne by the prosthetic
      limb during the first peak (weight acceptance) VGRF (mean = 1.08 +/- 0.08 BW; t =
      -4.999; p = 0.001) and significantly higher than the midstance VGRF (mean = 0.82
      +/- 0.07 BW; t = 5.401; p < 0.001). However, there was no significant difference
      between SWB and the second peak (push-off) VGRF generated by the prosthetic limb
      during walking (mean = 0.96 +/- 0.03 BW). It was concluded that clinical gait
      training may utilise SWB as a guide to an amputees' prosthetic weight bearing
      tolerance and requirements during walking.

PMID- 9285954
TI  - A new biomechanical method for determination of static prosthetic alignment.
AB  - A new static alignment method for trans-tibial prostheses is suggested using the
      individual load line as a reference. Standing posture and static alignment of 18
      experienced trans-tibial prosthetic users with good walking ability were
      determined and compared with 20 healthy persons. The individual load line was
      defined by means of the new Otto Bock alignment system "L.A.S.A.R. Posture". The
      sagittal standing posture of trans-tibial amputees and non-amputees differs.
      Normally only a prosthesis worn by the trans-tibial amputee and dynamically
      aligned over an extended period of time satisfies biomechanical rules of
      alignment. In contrast, prostheses aligned during one session in the traditional
      subjective manner seem to lack any recognizable biomechanical systematics.
      Initial results suggest the knee centre should be 10 to 30mm behind the load
      line, depending on patient's weight. This knee position is independent on the
      type of prosthetic foot.

PMID- 9285955
TI  - The effect of changing the inertia of a trans-tibial dynamic elastic response
      prosthesis on the kinematics and ground reaction force patterns.
AB  - The aim of this study was to assess, by means of gait analysis, the effect on the
      gait of a trans-tibial amputee of altering the mass and the moment of inertia of
      a dynamic elastic response prosthesis. One male amputee was analysed for four to
      five walking trials at normal and fast cadences, using the VICON system of motion
      analysis and an AMTI force plate. The kinematic variables of cadence, swing time,
      single support time and joint angles for the knee and hip on the affected and
      intact sides were analysed. The ground reaction force was also analysed. The
      sample size was limited to one as an example to indicate the changes which are
      possible through simply changing the inertial characteristics. Descriptive
      statistics are used to demonstrate these changes. Three mass conditions for the
      prosthesis were analysed m1: 1080g; m2: 1080 + 530g; m3: 1080 + 1460g. The m1
      condition is the mass of the prosthesis with no added weight while m2 and m3 were
      attachments of the same geometrical shape but were made from different materials.
      It was felt that the large mass range would highlight biomechanical adjustments
      as a result of its alteration. The effect on selected temporal characteristics
      were that as the speed increased the cadence changed and the affected side single
      support times as a percentage of the gait cycle were altered. The effect on the
      joint angles was also apparent at the hip and knee of both sides. The ground
      reaction force patterns were similar for all three mass conditions, though the
      impact peak which was evident in the intact limb was missing, indicating a shock
      absorbing property in the prosthesis. Clearly, changing the mass and moment of
      inertia has an effect on the kinematic variables of gait and should be considered
      when designing a prosthesis.

PMID- 9285956
TI  - ICEROSS--a consensus view: a questionnaire survey of the use of ICEROSS in the
      United Kingdom.
AB  - The management of the individual with a trans-tibial amputation has been strongly
      influence by the increasing use of the ICEROSS socket system over recent years.
      Despite this growth in clinical experience, there has been very little research
      into its place in current prosthetic practice, and prescribing activity is
      largely determined by personal experience. In order to formulate the current
      consensus view on the use of ICEROSS, questionnaire were sent to 42 doctors and
      43 senior prosthetists around the UK. The influence of 38 different factors on
      prescribing activity was assessed using a grading system (ranging from "primary
      indication" to "absolute contraindication"). An 85% response rate was achieved
      and no significant differences in response between the two professional groups
      were identified. Those factors considered by most to be positive indications for
      using ICEROSS were "pistoning", "shear-sensitive skin/split-skin grafts",
      "patient unsuccessful with supracondylar (s/c) or cuff suspension" and
      "insufficient suspension due to change in type or level of activity". Those
      considered by most to be absolute contra-indications were "ulceration/unhealed
      scars", "poor patient hygiene" and "poor commitment to prosthetic
      rehabilitation". This consensus of opinion is in keeping with the results of the
      few published adults of ICEROSS usage. There was a lack of consensus, however,
      about the use of ICEROSS in some situations, including skin complications. Whilst
      some consensus does exist about the use of ICEROSS, the results of this survey
      indicate significant variations in clinical practice with serve to illustrate the
      urgent need for data from prospective clinical trials.

PMID- 9285957
TI  - Analysis of torso movement of trans-femoral amputees during level walking.
AB  - The purpose of this study is to analyze the movement of unilateral trans-femoral
      amputees' gait and find patterns of compensated movement to accommodate the loss
      of locomotor power on one side. A 3-D analyzer system and force plate were used
      to measure 12 amputees. The main focus was to find characterized movement
      particularly of the upper body such as pelvis, shoulder and arms. It was Saunders
      et al. (1953), who said that the human body can be purposely divided into two
      subsystems in analyzing man's locomotion. This study, however is not to measure
      the level of function, but to evaluate the appearance of gait. Twelve markers
      were placed on the subjects, and two locations for measuring points were used to
      measure movement of the torso in three axis (X, Y, Z) without measuring the
      position of the centre of gravity. The two points were at shoulder level, and at
      pelvic level. Lissajou's figure was used to evaluate the movements at these two
      marks. The quality of the gait was determined through subjective evaluation by
      the author. Determination was made on two factors, one from observing the gait of
      the amputees and the other, patterns from their Lissajou's figure of two
      measuring points. Then they were categorized as good walker or "other". Good
      walkers had results at shoulder level which were closer to the symmetrical
      Lissajou's figure of normal walkers. Yet the symmetrical pattern was not present
      at the pelvis level for the good walker.

PMID- 9285958
TI  - The efficacy of the one-leg cycling test for determining the anaerobic threshold
      (AT) of lower limb amputees.
AB  - The aim of this study was to investigate whether or not the one-leg cycling test
      driven by the subject's sound leg as the exercise load method is an applicable
      method for determining the anaerobic threshold (AT) of lower limb amputees. To
      evaluate physical fitness, a graded exercise test that monitored gas exchange,
      ventilation and heart rate (HR) was performed in 51 unilateral lower limb
      amputees. AT was successfully measured for 42 out of 51 subjects, an 82.3%
      success rate. The average AT was 12.7 +/- 2.2 ml/kg/min, and the average HR at AT
      points was 117.7 +/- 16.2 beats/min. The average peak oxygen uptake was 20.1 +/-
      5.6 ml/kg/min, and the average peak HR was 145.1 +/- 22.4 beats/min. The peak HR
      exceeded the HR at AT by an average 27.4 beats/min, which indicates that a
      comparatively intense exercise load above the AT level is possible. The average
      AT was 40.9% of the predicted maximum oxygen uptake, which seems reasonable when
      compared to the reports of other researchers. These results suggested that the
      one-leg cycling test driven by the sound limb is of use as a method for
      determining the AT of lower limb amputees.

PMID- 9285959
TI  - A review of 42 patients of 16 years and over using the ORLAU Parawalker.
AB  - A 7 year retrospective review of 42 patients of 16 years or over using the ORLAU
      Parawalker has been conducted to establish the degree of long-term compliance in
      using the orthosis on a regular basis. Regular use was defined as putting the
      orthosis on at least once a week. All subjects had been supplied with an ORLAU
      Parawalker via the routine supply procedures adopted in Oswestry, and were
      followed up at regular 6 month intervals as part of the standard treatment
      regime. The records from routine follow-up were surveyed for those patients who
      were continuing to use their orthosis to establish age, length of time since
      supply of orthosis and cause of lesion. Average period of usage is calculated for
      those still using their orthosis, and for all patients in the study. Of the 42
      subjects, 32 were myelomeningocele patients with confirmed absence of innervation
      of hip extensors and abductors, the remainder being paraplegic patients with
      traumatic or acquired complete thoracic lesions. Compliance figures were
      extracted from the results, as were the minimum possible average periods of
      usage. The respective results were: of the 32 myelomeningocele patients 59.4%
      continued usage after an average period of 85.5 months, and of the 10 traumatic
      or acquired lesion patients 60% continued usage after an average period of 24.8
      months respectively, which gave a combined compliance of 59.5% after a minimum
      average 71.1 months of use. The performance or myelomeningocele patients suggests
      that their additional deformities do not lead to inferior compliance as adults
      and that a high proportion to continue to walk after adolescence.

PMID- 9285960
TI  - Heel lifting as a conservative therapy for osteoarthritis of the hip: based on
      the rationale of Pauwels' intertrochanteric osteotomy.
AB  - Patients with osteoarthritis of the hip were treated with a conservative therapy
      of heel lifting. Orthoses were applied on 35 hips in 33 subjects and the cases
      were followed for 23 months on average. Dramatic pain relief was reported, but
      the time required to reduce or completely relieve pain increased according to the
      stage of osteoarthritis. The radiological results were not satisfactory. During
      the follow-up, only two hips showed improvement, 22 showed no change, and 11
      deteriorated. The mechanism of heel lifting in relation to the hip joint was
      analysed, showing that pelvic obliquity was achieved and the trunk stabilized. In
      conclusion this simple orthosis was effective as a palliative therapy for
      osteoarthritis of the hip.

PMID- 9285961
TI  - A young female patient with reflex sympathetic dystrophy of the upper limb in
      whom amputation became inevitable.
AB  - Reflex sympathetic dystrophy (RSD) is characterized mostly by: (burning) pain,
      restricted range of motion, oedema and autonomic disturbances. Amputations in
      case of RSD patients should only be performed in cases of a dysfunctional limb,
      life threatening conditions such as untreatable infections or in cases in
      unbearable pain. The authors describe a patient in whom amputation became
      inevitable because of threatening infections.

PMID- 9285962
TI  - Park City molecular psychiatry conference, Park City, Utah, 2-4 February 1997.

PMID- 9285963
TI  - A linkage study of the N-methyl-D-aspartate receptor subunit gene loci and
      schizophrenia in southern African Bantu-speaking families.
AB  - Both direct and indirect evidence implicate excitatory amino acid
      neurotransmission in the aetiology of schizophrenia. The data are particularly
      suggestive for N-methyl-D-aspartate (NMDA) neurotransmission. Four of the six
      genes coding for subunits of the neural NMDA receptor have been mapped. We have
      studied segregation and allele sharing of markers in these four regions in a
      sample of southern African Bantu-speaking families multiply affected with DSM-III
      R schizophrenia. This population was chosen because anthropological and
      linguistic data suggest that it has diverged from a small initial population
      within the past 1000 years, making shared genetic aetiology more likely. We find
      positive LOD score maxima of 0.876 at a marker D9S1838 on chromosome 9q34.3 near
      the NMDAR1 central subunit gene, 0.758 at marker D17S784 on chromosome 17q25 near
      the NMDAR2C potentiating subunit gene, and 0.453 at marker D12S77 near the
      NMDAR2B gene on chromosome 12p12 when analysing affected samples only. Only the
      region of NMDAR2A, on chromosome 16p13, can be excluded in this population. There
      is evidence of increased allele sharing on chromosomes 9p34.3 and 17q25 using
      APM. Multipoint allele-sharing analysis using GENEHUNTER does not reject possible
      effects on chromosome 9q34.3, but does not support any involvement of chromosome
      17q25. We propose that the NMDA receptor may be involved in the genetic
      predisposition to schizophrenia in this population through covariation in several
      of the subunits, which is consistent with the genetic models of the inheritance
      of the disease.

PMID- 9285964
TI  - Schizophrenia, chronic hospitalization and the 5-HT2C receptor gene.
AB  - Frequency of a polymorphism in the coding region of the 5-hydroxytryptamine2C (5
      HT2C) receptor gene (HTR2C Xq24) was not significantly different in 122 unrelated
      Israeli schizophrenia patients compared with 180 control subjects matched for
      gender and ethnicity. However, proportion of time spent in hospital since the
      first admission was significantly greater in patients hemi- of homozygous for the
      5-HT2Cser allele than in patients carrying other genotypes (p = 0.006). The 5
      HT2Cser genotype conferred a 3.3-fold increased risk for lifetime hospitalization
      exceeding 10 years. Genetically determined variation in the 5-HT2C receptor may
      influence the clinical course and phenotypic expression of schizophrenia.

PMID- 9285965
TI  - Ciliary neurotrophic factor null mutation and schizophrenia in a Swedish
      population.
AB  - According to the maldevelopmental hypothesis, the neurotrophic factor system
      represents an important area which might be genetically and neurochemically
      involved in the etiopathogenesis of schizophrenic psychoses. Patients suffering
      from schizophrenic psychoses and control persons were genotyped for a null
      mutation of the ciliary neurotropic factor gene. There were no significant
      differences in the allelic and genotypic distributions in the total schizophrenic
      and control samples. However, there was a negative association with a family
      history of psychosis. Thus, it cannot be excluded that this genetic variant
      represents a vulnerability marker for specific schizophrenic subtypes. The
      development of valid diagnostic instruments based on biological criteria is
      crucial for schizophrenia research; more homogeneous subgroups are more likely to
      represent distinct nosological entities than the heterogenous group of diseases
      presently categorized as schizophrenia.

PMID- 9285966
TI  - Association between schizophrenia and a microsatellite polymorphism at the
      dopamine D5 receptor gene.
AB  - An association study of 97 patients with DSM-III-R schizophrenia and 97 matched
      controls was performed using a polymorphic microsatellite repeat at the dopamine
      D5 receptor gene. We observed a significant difference between the allele
      frequencies of patients and controls (chi 2 = 23.4, df = 12, p = 0.019). This
      reflects an excess of allele 4 (140 bp) in the patients when compared with the
      control sample (chi 2 = 7.087, p < 0.01; odds ratio = 2.98, 95% CI 1.29-6.86).
      However, this association remains tentative until confirmation in other samples.

PMID- 9285967
TI  - Alcoholism and gene polymorphisms related to central dopaminergic transmission in
      the Japanese population.
AB  - We examined the association between gene polymorphisms related to central
      dopaminergic transmission and alcoholism in the Japanese population. Polymorphic
      gene loci examined included those encoding the dopamine D2 receptor (NcoI site
      and Ser-Cys site), the dopamine D3 receptor (BalI site), the dopamine D4 receptor
      (48 bp tandem repeat) and the dopamine transporter (40 bp tandem repeat). The
      genotype distribution at the NcoI site in the dopamine D2 receptor gene differed
      significantly (p < 0.5) between alcoholic patients and control subjects. The
      frequency of 7 repeats at the 40 bp/DAT tended to be higher (p < 0.1), and that
      of 9 repeats tended to be lower (p < 0.1) in alcoholic patients than in control
      subjects. The possible effects of dopamine-related gene polymorphisms, which
      might predispose individuals to alcoholism, are discussed.

PMID- 9285968
TI  - No association between the dopamine D2 receptor gene and Korean alcoholism.

PMID- 9285969
TI  - Efficacy versus effectiveness.

PMID- 9285970
TI  - Treating older adults with psychotic symptoms.

PMID- 9285971
TI  - Multimodal cognitive-behavior therapy for borderline personality disorder with
      self-injurious behavior.

PMID- 9285972
TI  - From chlorpromazine to olanzapine: a brief history of antipsychotics.

PMID- 9285973
TI  - Telemedicine in emergency psychiatry.

PMID- 9285974
TI  - Savings from a Medicaid carve-out for mental health and substance abuse services
      in Massachusetts.
AB  - OBJECTIVE: The study examined the financial performance of a managed behavioral
      health care organization responsible for mental health and substance abuse
      services under the Massachusetts Medicaid program. Financial performance is
      considered in light of incentives in the contract between the managed care firm
      and Medicaid. METHODS: Data on the financial performance of the managed care
      organization were obtained from documents related to a recent rebidding of the
      contract and other publicly available documents. Financial incentives associated
      with claims costs and administrative services are also reported. RESULTS:
      Spending by the managed care organization was about 25 percent lower than
      projected expenditures adjusted for inflation. Explicit financial incentives
      associated with cost reduction did not give the managed care organization strong
      inducements to attain these savings. The profit and loss features based on cost
      targets were quite limited. The organization had a much greater incentive and
      opportunity to make profits by conserving its administrative costs rather than by
      controlling Medicaid claims costs. CONCLUSIONS: In light of the contract's weak
      cost-saving incentives, it may be surprising that so much was saved. One
      explanation is that it was easy to achieve such savings in a state with high
      expenditures. However, in examining the particular amounts saved, it is clear
      that the organization came close to contract targets even when incentives to
      achieve them were weak. The authors label this behavior "managing to the
      contract" and discuss some reasons why a managed care organization might behave
      in this way and the implications this behavior has for contract design.

PMID- 9285975
TI  - Impact of risperidone on the use of mental health care resources.
AB  - OBJECTIVE: The effects of risperidone treatment on health care utilization and
      treatment costs were examined among patients with treatment-refractory
      schizophrenia or schizoaffective disorder. METHODS: Data from the Santa Clara
      County Mental Health Department were used to measure inpatient and ambulatory
      services and outpatient medications related to the treatment of mental disorders.
      Data for 139 patients were analyzed for periods before and after initiation of
      risperidone treatment. A mean +/- SD of 14 +/- 2.1 months of data were available
      in both the before and after periods, for a mean total study period of 28 months.
      RESULTS: The patients' mean age was 40 years (range, 18 to 78 years), and 46
      percent were women. After the start of risperidone treatment, days in acute care
      inpatient facilities were reduced by 26 percent, and days in residential
      treatment were reduced by 57 percent. These reductions were accompanied by an
      increase in the use of lower-cost services, such as community living, treatment
      planning, and partial hospital-day treatment. There was a 3.4 percent increase in
      total psychiatric health care costs after initiation of treatment with
      risperidone. CONCLUSIONS: Overall, risperidone treatment resulted in a shift or
      resource utilization from provider-delivered services to pharmaceutical care
      without a significant change in total health care cost.

PMID- 9285976
TI  - Responses of direct-care paraprofessional mental health staff to hypothetical
      ethics violations.
AB  - OBJECTIVE: The study examined the responses of paraprofessional mental health
      direct-care staff to hypothetical ethics violations in the care of persons with
      mental illness. METHODS: Eighty-five paraprofessionals in a medium-sized
      Midwestern psychiatric facility responded to a survey that presented ten
      hypothetical ethics violations varying in severity. For each scenario,
      respondents were asked to indicate the likelihood that they would ignore the
      violation, confront the care provider who had acted unethically, or report the
      violation to an immediate supervisor or to someone in authority over the
      immediate supervisor. The survey also assessed the paraprofessionals' perceived
      skills, knowledge, and need for additional training in professional ethics.
      RESULTS: Survey respondents were significantly less likely to ignore situations
      of moderate or high severity, compared with situations of low severity, and were
      significantly more likely to report a moderately severe or highly severe incident
      than an incident of low severity. CONCLUSIONS: The response of mental health
      paraprofessionals to hypothetical ethics violations suggests that they are able
      to recognize and evaluate the severity of ethics violations and weigh the
      potential effects of their responses. However, their responses to hypothetical
      situations may not reflect how they would respond to actual ethics violations on
      the job.

PMID- 9285977
TI  - Melvin Sabshin reflects on two decades at the helm of the APA. Interview by John
      A. Talbott and Howard H. Goldman.

PMID- 9285978
TI  - Risk appraisal and management of violent behavior.
AB  - OBJECTIVE: To help clinicians enhance the safety of the public, hospital staff,
      and patients and improve patient management, this article briefly reviews recent
      empirical work on appraisal of the risk of violence and the management of violent
      individuals. METHODS: Research on the prediction, management, and treatment of
      violent persons published in the last decade was reviewed. RESULTS: Risk
      appraisal research indicates that violence is predictable in some populations.
      The factors most highly and consistently related to risk are historical,
      including age, sex, past antisocial and violent conduct, psychopathy, aggressive
      childhood behavior, and substance abuse. Major mental disorder and psychiatric
      disturbance are poor predictors of violence. Actuarial methods are more accurate
      in predicting risk than unaided clinical judgment, which is a poor index. The
      Violence Risk Appraisal Guide has been shown to be a reliable and accurate
      actuarial instrument. Well-controlled studies have shown the effectiveness of
      behavior therapy and of behavioral staff training programs to reduce violence by
      persons in institutions, chronic psychiatric patients, and other populations.
      Otherwise, little is known about what psychotherapeutic or pharmacological
      treatments reduce violent recidivism by which clients under what circumstances.
      Recent work on the neurophysiology of aggression holds exciting promise but does
      not yet provide a scientific basis for prescriptive treatment. CONCLUSIONS: The
      most exciting and promising avenues for research on the management of violence
      lie in the joining of two scientific paths to understanding violence--biology and
      psychology.

PMID- 9285979
TI  - Use of the NOSIE to predict assaults among acute psychiatric patients. Nurses'
      Observational Scale for Inpatient Evaluation.
AB  - OBJECTIVE: The study evaluated the Nurses' Observational Scale for Inpatient
      Evaluation (NOSIE), the Brief Psychiatric Rating Scale (BPRS), the Mini Mental
      State Examination (MMSE), and other measures as predictors of assaults that
      occurred during psychiatric hospitalization. METHODS: On admission, the MMSE was
      administered to 335 acutely ill psychiatric patients, and diagnostic and
      demographic data were recorded. Immediately after admission, patients were rated
      by nurses using the NOSIE and by psychologists using the BPRS. Patients who
      committed assaults during hospitalization (N = 47) and those who did not were
      compared, and relationships between several variables and assaults were evaluated
      by t tests, Mann-Whitney U tests, chi square tests, and analyses of variance.
      RESULTS: A high score on the irritability factor of the NOSIE and failure to
      complete the MMSE correctly predicted the occurrence or nonoccurrence of assault
      81 percent of the time. None of the other variables examined were significantly
      related to assaults, including total scores on the BPRS and MMSE, psychiatric
      diagnosis, and several demographic variables. CONCLUSIONS: Scores on a test of
      distress level shortly after admission and failure to complete the MMSE on
      admission can help the clinician predict who will later engage in an assault.

PMID- 9285980
TI  - Early-onset substance abuse and community violence by outpatients with chronic
      mental illness.
AB  - OBJECTIVE: This study examined the relationship between violence and substance
      abuse among patients with chronic mental illness living in the community.
      METHODS: All referrals over a one-year period to an urban assertive community
      treatment team were evaluated systematically with a standardized intake protocol.
      Thirty-seven patients with a history of violence in the community were compared
      with 27 patients without such a history on a variety of clinical and demographic
      variables. RESULTS: More than half of the patients (58 percent) had a history of
      violence in the community. The only significant differences between those with a
      history of violence and those without involved alcohol or drug use. The single
      best predictor of violence was the onset of alcohol or drug abuse in late
      childhood or early adolescence. CONCLUSIONS: In this sample, very early onset of
      substance abuse among people who developed mental illness was associated with the
      greatest risk of community violence. Thus at least some of the causal
      determinants of violence in this sample may precede the onset of adult mental
      illness.

PMID- 9285981
TI  - A hospital-based domestic violence group.
AB  - OBJECTIVE: This study of a public-hospital-based drop-in group for women who were
      victims of domestic violence sought to determine whether the group attracted
      clients from the target population of patients in the medical system, to identify
      characteristics of the battered women attending the group, and to examine whether
      the group shared the same characteristics as battered women who were evaluated in
      other contexts within the medical system. METHODS: Fifty-nine clients attending a
      domestic violence group at an urban public hospital completed questionnaires on
      referral sources, demographic characteristics, needs, and satisfaction. Included
      for comparison were clinical data on referral sources and demographic
      characteristics for 224 battered women evaluated by clinical social workers at
      the hospital and affiliated clinics. RESULTS: Referral patterns differed for the
      two groups: the majority of the social work cases were referred from the
      emergency room, and the majority of the referrals to the domestic violence group
      were from outside agencies, informal sources, and the hospital's inpatient units.
      A greater proportion of women attending the group were white, divorced or
      separated, and no longer living with their partners. Among the social work cases,
      the women were more likely to be ethnic minorities, single, and still living with
      their partners. CONCLUSIONS: The domestic violence group intervention attracted a
      different subgroup of battered women than did the social work intervention, which
      was likely due to differences in readiness to initiate change and to cultural
      barriers to group participation.

PMID- 9285982
TI  - Traumatic reactions as predictors of posttraumatic stress six months after the
      Oklahoma City bombing.
AB  - OBJECTIVE: This study attempted to identify remembered reactions of Oklahoma City
      residents at the time of the April 1995 terrorist bombing that predicted later
      development of posttraumatic stress symptoms. METHODS: Eighty-six adults who
      sought help for distress related to the bombing six months after it occurred
      completed a survey about demographic characteristics, level of exposure to the
      event, symptoms of grief, retrospective reports of reactions at the time of the
      trauma, current posttraumatic stress symptoms, and coping strategies. To identify
      immediate bombing reactions predictive of later distress, retrospective reports
      of reactions to the trauma were correlated with current posttraumatic stress
      symptoms. Multiple regression analysis was used to determine which reactions
      predicted the emergence of posttraumatic stress symptoms. RESULTS: Reactions of
      being nervous and being upset by how other people acted when the bombing occurred
      accounted for about one-third of the total variation in posttraumatic stress
      symptom scores and thus were major predictors of posttraumatic stress.
      CONCLUSIONS: These results differ from those of other studies in which
      peritraumatic dissociation, or dissociation at the time of the event, was more
      predictive than anxiety for developing later distress. The results suggest that
      persons who experience significant anxiety at the time of the traumatic event may
      continue to experience distress. Those who are overly concerned about others'
      actions may be showing diminished interpersonal trust, evidence of terrorism's
      ability to erode social harmony.

PMID- 9285983
TI  - Use of the Brief Psychiatric Rating Scale to measure success in a psychosocial
      day program.
AB  - This study contrasted six subscales of the Brief Psychiatric Rating Scale (BPRS)
      to determine their sensitivity to psychosocial treatment outcome. An expanded
      version of the BPRS was administered to 216 clients on admission to a day
      program. The subscale measuring hostility and suspiciousness discriminated at
      intake clients who were therapeutically discharged from clients who did not
      complete the program and predicted discharge status after the investigators
      controlled for the effects of demographic variables. Significant reductions in
      scores were obtained on five subscales for a subset of clients to whom the BPRS
      was readministered before discharge. The results support the use of the expanded
      BPRS as an evaluative tool in psychosocial rehabilitation programs.

PMID- 9285984
TI  - Mnemonics for DSM-IV personality disorders.
AB  - The paper presents several mnemonics to assist clinicians in recalling DSM-IV
      diagnostic criteria for personality disorders. The mnemonics are acronyms, and
      each letter is associated with a specific criterion. Each acronym reflects a
      facet of the related disorder; for example, the acronym for the diagnostic
      criteria for paranoid personality disorder is SUSPECT, and for histrionic
      personality disorder it is PRAISE ME. The mnemonics have been used to teach
      students and residents the conceptual nature of DSM-IV disorders and to help them
      remember the criteria.

PMID- 9285985
TI  - Family planning outcomes of male chronically ill psychiatric outpatients.
AB  - To assess contraceptive use and child-rearing outcomes, a semistructured
      interview was given to 92 male psychiatric outpatients and to 92 matched control
      subjects without major mental illness. Compared with the control subjects, the
      patients were significantly more likely to have given up children less than 16
      years of age for others to raise. Thirty-three percent of the patients who did
      not want to father children reported that contraception had not been used when
      they last had heterosexual intercourse. The findings suggest that psychiatrists
      should identify and reduce male psychiatric patients' risk of fathering unwanted
      children.

PMID- 9285986
TI  - Risk factors for parasuicide among psychiatric inpatients.
AB  - To improve suicide prevention during hospitalization, this study examined risk
      factors for parasuicide among psychiatric inpatients. A group of 58 psychiatric
      inpatients (19 with schizophrenia, 20 with depression, and 19 with other
      diagnoses) who displayed suicidal behavior during hospitalization were compared
      with two control groups of nonparasuicidal inpatients. For inpatients with
      schizophrenia, a history of parasuicide was a risk factor; for those with
      depression, it was suicidal behavior on admission; and for patients with other
      diagnoses, it was violence during hospitalization.

PMID- 9285987
TI  - Identification of the domestic mite fauna of Puerto Rico.
AB  - This study was conducted to identify the domestic mite fauna of Puerto Rico. A
      total of 57 dust samples were collected from mattresses in homes of 11 cities on
      the Island. The analysis of the samples revealed that 73.70% of the mattress
      samples had at least one mite species. The identified species include:
      Dermatophagoides pteronyssinus (45.6%), Blomia tropicalis (31.6%), Cheyletus sp.
      (19.3%), Dermatophagoides farinae (17.5%), Euroglyphus maynei (5.3%),
      Dermatophagoides sibonei (1.8%), Dermatophagoides sp. (1.8%), Suidasia melanensis
      (1.8%) and mite species that were not identified (5.3%). Differences in the
      geographical distribution of mites showed that only Blomia tropicalis is more
      frequently in the northern (43%) than in the southern region (19%) of Puerto Rico
      (OR 3.36, p, 0.046). This finding can be explained by the fact that in the
      northern region the relative humidity is significantly higher that in the
      southern region (p < 0.001). No significant differences were observed for other
      species or in the total mite counts between the northern and southern regions.
      The small sample size of this study may explain the lack significance for some of
      the differences found. Nevertheless, our results indicate that the domestic mite
      fauna is composed of several clinically important species, their numbers are high
      enough to be considered in the sensitizing levels, and the diversity of these
      species is comparable to other observations in the Caribbean areas, and in the
      southern states in the continental US. Based upon our results, we recommend that
      when performing the skin test in Puerto Rico, extracts from the identified local
      domestic mite species be included in the allergen panel. This may prove useful in
      the aid for the diagnosis and management of atopic conditions.

PMID- 9285988
TI  - The epidemiology of mental disorders in the adult population of Puerto Rico.
AB  - OBJECTIVES: The main objective of the manuscript is to present a review of the
      literature of the psychiatric epidemiological studies carried out in Puerto Rico
      in the last decade. BACKGROUND: Data from three major epidemiological surveys
      carried out in the last decade is presented which provide evidence against prior
      long standing observations that Puerto Ricans reported higher levels of
      psychiatric symptomatology as compared to other populations and ethnic groups in
      the United States. METHODS: The studies selected for review were the universe of
      population epidemiological studies carried out in Puerto Rico in the last decade.
      All studies used island wide probability sampling procedures to select the study
      population. RESULTS: Rates of psychiatric disorders in Puerto Rico were found to
      be significantly different from those obtained in United States communities.
      Exceptions were somatization disorder and symptoms which were found to be
      significantly more common in Puerto Rico and drug abuse/dependence which was
      found to be considerably less common in the island as compared to the Unites
      States adults in the age range of 17 to 67 years old. CONCLUSION: In spite of
      several indicators of social disruption in the island, the prevalence of most
      psychiatric disorders does not appear to be more prevalent than in other
      communities in the United States and other parts of the world. Risk factors for
      mental disorders are also similar, although sex ratios for gender linked
      disorders are more marked in the island.

PMID- 9285990
TI  - The endothelium in health and in cardiovascular disease.
AB  - Significant new findings in the last decade have demonstrated that the vascular
      endothelium is an important regulatory organ in maintaining cardiovascular
      homeostasis and that endothelial dysfunction is present in several cardiovascular
      diseases. With the production of multiple vasoactive substances the normal
      endothelium modulates the tone of the underlying vascular smooth muscle. These
      include endothelium-derived relaxing factors such as prostacyclin (PG1(2)),
      nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) and
      vasoconstrictors such as endothelin-1 and angiotensin II. The antiplatelet,
      antithrombotic and antifibrinolytic properties of the normal endothelium
      contribute to the maintenance of the fluidity of the blood. Activation or injury
      to the endothelial cells disrupts the function of the endothelial cells leading
      to the development of endothelial dysfunction. Endothelial dysfunction is
      accompanied by vasospasm, thrombosis, and atherosclerosis. It is present in
      cardiovascular diseases such as hypertension, atherosclerotic heart diseases,
      congestive heart failure and many others. It has been shown that some therapeutic
      effects of drugs such as angiotensin-enzyme inhibitors is in part due to the
      overcoming of endothelial dysfunction.

PMID- 9285989
TI  - Magnetic resonance angiography of giant aneurysms. Pitfalls and surgical
      implications.
AB  - OBJECTIVE: Magnetic resonance angiography (MRA) can be used to identify cerebral
      aneurysms. In this report, techniques for the diagnosis of giant cerebral
      aneurysm using MRA are discussed. Pitfalls in the diagnosis are presented.
      BACKGROUND: Giant cerebral aneurysms, which can be partially or totally
      thrombosed, or may have slow flow, can be confusing and difficult to diagnose.
      Giant cerebral aneurysms with thrombus formation, produce an artifact in time-of
      flight MRA in which the thrombus simulates flowing blood. METHOD: Five
      consecutive patients with the suspected diagnosis of giant cerebral aneurysm by
      MRA were analyzed. Neuroradiological studies were reviewed. RESULTS: In 20% of
      the cases, the correct diagnosis was made using MRA; in 60% of the cases, a
      correct diagnosis was made, but the size or the presence of flow was not
      correctly identified; in 20% of the cases, the diagnosis was incorrect. Four
      patients with giant cerebral aneurysms who presented a diagnostic and a
      therapeutic challenge are discussed. CONCLUSION: Unless MRA findings are combined
      with computed tomography scan and magnetic resonance imaging findings, the exact
      nature of the sac contents of giant cerebral aneurysms cannot be identified.

PMID- 9285991
TI  - Intention to postpone sexual initiation among Puerto Rican female adolescents.
AB  - The purpose of this analysis is to examine the factors associated with intentions
      to initiate sexual intercourse among a group of female high school students in
      Puerto Rico. A large metropolitan high school was purposively selected for the
      study. The mean age of the girls who participated in the study (N = 133) was 16.
      13% of the surveyed girls reported having had intercourse at some point in their
      lives. 45% indicated when answered that they were sure they would not initiate
      sex during the next year; 18% answered that it probably would not happen; and the
      others (28%) responded with an even 50-50 chance or more that it will probably
      happen. A multiple regression/correlation analysis showed that the mother's
      traditional sexual values along with the teen's own conventional behavior,
      traditional sexual values as well as a perception of conventional behavior by
      their peers were related to a lower expectation of sex initiation.

PMID- 9285992
TI  - Neonatal lupus erythematosus.
AB  - This is a case of an infant with neonatal lupus erythematosus who presented the
      characteristic cutaneous lesions without evidence of systemic involvement. NLE is
      a rare condition which affects newborn infants from mothers who may me
      asymptomatic or have a connective tissue disease, with or without autoantibodies
      to extractable nuclear antigens Ro (SS-A), LA (SS-B) or ribonucleoproteins. The
      skin lesions are usually annular in configuration and resemble those of subacute
      cutaneous lupus erythematosus. Congenital complete heart block (CHB) may be
      present in addition to the cutaneous lesions. This is a review of NLE focusing on
      its clinical manifestations, serologic markers, pathogenesis and treatment.

PMID- 9285993
TI  - The use of gadolinium in the MR evaluation of soft tissue tumors.
AB  - MRI has emerged as the preferred modality for the imaging evaluation of
      musculoskeletal tumors. Although there is general agreement on the value of MR in
      detection, diagnosis and staging, the use of intravenous contrast in the
      evaluation of soft-tissue tumors and tumor-like masses remains controversial. The
      purpose of this review is to highlight these controversies, to put them in
      perspective, and to make recommendations for the use of gadolinium-enhanced
      imaging. The following specific areas will be addressed: (1) general
      considerations in the evaluation of soft tissue tumors, (2) added specificity in
      diagnosis, (3) response to chemotherapy, (4) evaluation for local recurrence
      after surgery and/or radiation therapy, and (5) selection of biopsy site.

PMID- 9285995
TI  - Safety and medico-legal implications of intra-articular gadolinium use.

PMID- 9285994
TI  - The use of intravenous contrast in MRI of extremity infection.
AB  - Infection of the musculoskeletal system encompasses a variety of conditions,
      affecting skin, fascia, muscle, joints, tendon sheaths, and bone. In addition to
      features unique to each tissue site, these processes vary with respect to
      organism virulence, overall host condition, and the condition of the extremity
      itself, particularly its circulation. Treatment of musculoskeletal infection
      varies according to these features, and with respect to the presence of
      devitalized tissue. Unfortunately, while clinical examination is accurate for the
      presence of infection as a process in most circumstances, it lacks specificity
      for the variety of disorders within the spectrum of extremity infection. MRI
      examination using intravenous contrast is becoming the preferred modality to
      study complicated extremity infections, since it provides an accurate portrayal
      of the extent of osseous and non osseous involvement, and identifies areas of
      necrosis. This information provides a basis from which clinicians may more
      accurately choose from among treatment options.

PMID- 9285996
TI  - MR arthrography of the rotator cuff and labral-ligamentous complex.
AB  - In MR imaging of the shoulder, diagnostic success requires the delineation of
      complex anatomic structures and the demonstration of subtle abnormalities.
      Magnetic resonance (MR) arthrography extends the capabilities of conventional MR
      imaging because contrast solution separates intra-articular structures and
      outlines abnormalities. There are several major contributions of MR arthrography.
      In assessment of the rotator cuff, arthrographic MR images enable the accurate
      differentiation of full-thickness tears from other cuff abnormalities, as well as
      the determination of tendon quality. In shoulders with suspected glenohumeral
      instability, arthrographic MR images show the locations of labral tears relative
      to the origins of glenohumeral ligaments. This article illustrates normal
      arthrographic MR features of the shoulder as well as common pathological
      disorders of the rotator cuff and labral-ligamentous complex.

PMID- 9285997
TI  - Current concepts of MR arthrography of the hip.
AB  - MR arthrography is a recent addition to the imaging evaluation of the hip. The
      combination of joint distention and multiplanar imaging provides a detailed
      assessment of the intraarticular structures, most importantly the acetabular
      labrum. An acetabular labral tear is a potential cause of hip pain in patients
      with an otherwise normal joint, or patients with underlying pathology such as
      developmental dysplasia. A summary of the current concepts regarding
      identification of labral degeneration, labral tears and detachments, and
      potential pitfalls is presented in this article.

PMID- 9285998
TI  - Indirect MR arthrography: techniques and applications.
AB  - Indirect MR arthrography is a simple noninvasive alternative to direct MR
      arthrography and can potentially alter the diagnostic work-up of several
      diseases. Based on current knowledge, these diseases include rotator cuff tears.
      glenoid labrum tears, recurrent tears of the menisci and classification of
      osteochondritis dissecans. The technique is recommended for inclusion in the MRI
      diagnostic array, and may obviate the need for invasive direct MR arthrography.
      The technique and applications of indirect MR arthrography are summarized in this
      article, based on our own experiences and that described in the current
      literature.

PMID- 9285999
TI  - The use of gadolinium in the MR imaging of bone tumors.
AB  - Before determining the role of gadolinium in the evaluation of the solitary bone
      tumor, the practicing radiologist needs to determine which solitary bone lesions
      merit further evaluation with magnetic resonance imaging and why further imaging
      is required. A practical approach in applying magnetic resonance imaging to the
      indeterminate solitary bone lesion is outlined in this article, which serves as a
      guideline for logical and consistent application of MR imaging for this purpose.
      Although seemingly widely used, gadolinium appears to add little to the
      diagnostic sensitivity of specificity of MR with respect to solitary bone
      lesions. For selective tumors, such as osteosarcoma, gadolinium offers the
      potential for determining the efficacy of chemotherapy, by evaluating tumor
      necrosis prior and subsequent to chemotherapy. In select situations, especially
      sarcomas close to joints, gadolinium may aid and augment other pulse sequences in
      determining whether tumor resection should be intra- or extra-articular. However,
      gadolinium has a limited role in the evaluation of the solitary bone tumor, and
      its use should be the exception rather than the rule.

PMID- 9286000
TI  - Relationships among alcohol availability, drinking location, alcohol consumption,
      and drinking problems in adolescents.
AB  - We examined relationships among perceived alcohol availability, drinking
      location, alcohol consumption, and drinking problems. Subjects were 3,372
      adolescent drinkers, ages 16-18, who participated in the Communities Mobilizing
      for Change on Alcohol Project baseline survey. Mixed-model regression was
      employed to identify predictors of alcohol consumption and drinking consequences.
      Perceived alcohol availability was significantly associated with higher levels of
      alcohol consumption for males. Drinking in a public location with higher levels
      of alcohol consumption for females. Results underscore the importance of youth
      alcohol assessibility.

PMID- 9286001
TI  - Reasons for drinking versus outcome expectancies in the prediction of college
      student drinking.
AB  - This study developed a Reasons for Drinking Scale (RFD) with three factorially
      derived subscales, Social Camaraderie, Mood Enhancement, and Tension Reduction,
      among a university student sample. These scales were then compared to a measure
      of alcohol expectancies, the Alcohol Expectancy Questionnaire (AEQ), as
      predictors of several measures of alcohol use. The RFD accounted for more of the
      variance on all alcohol measures than the AEQ. Results are discussed in terms of
      reasons for drinking as a more direct assessment of cognitive motivations for
      drinking than outcome expectancies.

PMID- 9286002
TI  - Heroin addicts in the community and in treatment compared for severity of
      problems and need for help.
AB  - This article focuses on differences and similarities between heroin addicts in
      the community and in three types of treatment and a model for help-seeking. Data
      were collected with the Addiction Severity Index (ASI). Analyses concentrated on
      severity of problems, concern regarding the problems, and need for help. The
      results indicate that differences exist across the groups. Psychological and
      social problems were more frequently reported by addicts applying for inpatient
      treatment. Occupational, health, and legal problems appeared not to be triggers
      for seeking professional help.

PMID- 9286003
TI  - Evaluating the impact of a clinical training program in the addictions.
AB  - This research examined students who were enrolled in a specialized addiction
      treatment training program to evaluate the impact of this year-long internship
      experience on their professional lives. Achieving an 87.5% survey completion
      rate, the vast majority of program graduates assessed the overall training
      program and its component activities very positively. The topics and activities
      associated with "drug dependence" were evaluated more positively than the
      training events associated with pathological gambling. Furthermore, the majority
      of program graduates obtained jobs in the addiction field. As a result of the
      training program, approximately 74.5% of respondents stated that they had changed
      their beliefs about addiction. In addition, many respondents commented that their
      participation in the program changed their stereotypes of people with addiction.
      The findings provide suggestions and guidance for other clinical training
      programs that can gain from the experiences of fellows who studied at the Norman
      E. Zinberg Center for Addiction Studies.

PMID- 9286005
TI  - Differential perceptions of drinkers of alcoholic beverages by Mexican-Americans
      and non-Hispanic whites.
AB  - Random samples of 534 Mexican-Americans and 616 non-Hispanic Whites were
      interviewed over the telephone in San Jose, California and in San Antonio, Texas.
      Mexican-Americans tended to favor most frequently negative traits for their
      perceptions of drinkers than non-Hispanic Whites. Excessive drinkers were
      perceived most frequently in generally negative fashion by members of both ethnic
      groups although they were also perceived as happy persons. Highly acculturated
      Mexican-Americans reported perceptions of drinkers and of excessive drinkers that
      differed from those held by the less acculturated Mexican-Americans and that
      resembled those held by the non-Hispanic White respondents.

PMID- 9286004
TI  - Incidence and prevalence of illegal drug use in Switzerland in the 1980s and
      early 1990s: an analytical study.
AB  - The Swiss registry of charges concerning illegal trade and consumption of
      narcotics offers the possibility of monitoring the incidence and prevalence of
      illegal drug use in Switzerland. Of course, the relation between the number of
      charges against users of illegal drugs and the number of users is unknown and may
      vary in time and space. This makes it difficult to estimate the prevalence of
      consumption from law enforcement data, but it does not hinder the estimation of
      incidence if the numbers of first and subsequent charges are known. This is
      demonstrated by employing a dynamic model with two compartments which represent
      the not yet charged and the charged users. In contrast to methods which rely on
      treatment admission data, the new method can detect changes of incidence without
      time lag. Prevalence estimates can be obtained if the charge frequency
      distribution is known, as it is for Switzerland from 1990 to 1994. A theoretical
      distribution is fitted to the data which are available for all illegal drugs as
      well as for heroin and/or cocaine. This leads to estimates of the populations of
      users of illegal drugs in general and of heroin and/or cocaine.

PMID- 9286006
TI  - Sensitivity of MCMI-III Scales T (drugs) and B (alcohol) in detecting substance
      abuse.
AB  - The sensitivity and specificity of MCMI-III Scales T (drug dependence) and B
      (alcohol dependence) were evaluated with patients (N = 164) in an inpatient
      substance user treatment program. The sensitivity levels of these two scales
      improved significantly compared to previous research using the MCMI I and MCMI II
      Scales T and B, which had not achieved sensitivity values above .50. However,
      specificity for detecting alcoholism among drug misusers was lower compared to
      MCMI I and II studies. Results suggest improved diagnostic sensitivity with the
      MCMI-III in diagnosing substance misuse, but lowered efficiency in ruling out the
      disorder.

PMID- 9286007
TI  - The needs of women with substance use problems: an expanded vision for treatment.
AB  - Although the number of females served in United States treatment programs for
      substance use has increased over the last decade, women continue to be
      underrepresented. This suggests that the prevalent treatment models, which tend
      to be male-oriented, may not provide appropriate strategies to meet women's
      needs. Substance use problems in women appear to be multideterminded phenomena in
      which genetics, familial history, psychosocial issues, and other environmental
      factors play contributing roles. Working from a relational theoretical model of
      female psychosocial development, a continuum of expanded services addressing the
      entire context of women's lives is discussed.

PMID- 9286008
TI  - The rules of drug taking: wine and poppy derivatives in the ancient world. VII. A
      ritual use of poppy derivatives?
AB  - Besides fertility, poppies have been used to symbolize sleep, night, and death.
      Consistent with the agrarian origin of their ritual use, poppies also became a
      symbol of reincarnation. Several literary and iconographic sources, in particular
      of the early Roman imperial age, are here interpreted as evidence that poppy
      derivatives were ingested during mystery rites. The reversible narcotic effects
      of poppy derivatives should have allowed a "realistic" representation of death
      and reincarnation, as intended by the Orphic belief of the transmigration of
      souls.

PMID- 9286010
TI  - Reduction of the clutter component in Doppler ultrasound signals based on
      singular value decomposition: a simulation study.
AB  - In pulsed Doppler ultrasound systems, the ultrasound radiofrequency (RF) signals
      received can be employed to estimate noninvasively the time-dependent blood
      velocity distribution within and artery. The RF signals are composed of signals
      originating from clutter (e.g., vessel walls) and scatterers (e.g., red blood
      cells). The clutter, which is induced by stationary or slowly-moving structure
      interfaces, must be suppressed to get reliable estimates of the mean blood flow
      velocities. In conventional pulsed Doppler systems, this is achieved with a
      static temporal high-pass filter. The static cut-off frequency and the roll-off
      of these filters cause the culture not always to be optimally suppressed. This
      paper introduces a clutter removal filter that is based on Singular Value
      Decomposition (SVD). Unlike conventional high-pass filters, which take into
      account only the information of the temporal direction, the SVD filter makes use
      of the information of the temporal and spatial directions. The advantage of this
      approach is that it does not matter where the clutter is located in the RF
      signal. The performance of the SVD filter is examined with computer-generated
      Doppler RF signals. The results are compared with those of standard linear
      regression (SLR) filter. The performance of the SVD filter is good, especially if
      a large temporal window (i.e., approximately 100 RF signals) is applied, which
      improves the performance for low blood flow velocities, A major disadvantage of
      the SVD filter is its computational complexity, which increases considerably for
      larger temporal windows.

PMID- 9286009
TI  - Childhood sexual trauma and substance misuse: a pilot study.
AB  - This research investigates the type of and extent to which additional problematic
      experiences and behaviors are associated with a history of both substance misuse
      and childhood sexual abuse. In a recent study of women undergraduate students, 30
      years and older, 15 disclosed a history of problematic alcohol and/or drug use.
      Of these, 10 had experienced sexual trauma as children; five had not. This report
      compares these two subsamples with respect to problematic experiences and
      behavior. Implications for counseling and research are discussed.

PMID- 9286011
TI  - Ultrasonic measurement of differential displacement and strain in a vascular
      model.
AB  - The potential in intravascular ultrasound imaging for characterizing regional
      arterial elasticity was examined in an experimental tissue-equivalent vessel
      model. Differential intrawall displacement measurement, the first step in
      regional elasticity determination, was investigated using a crosscorrelation
      tracking algorithm. Calibration studies showed that tracking accuracy varied
      significantly with tracking direction (axial versus lateral) and position in the
      field of the transducer. Midfield geometric error in the axial direction for a
      nominal displacement of 100 microns was 5.5 microns whereas the corresponding
      error in the lateral direction was 31.7 microns. Displacement was tracked in
      serial intravascular images of vessel phantoms acquired during stepwise
      pressurization experiments from 0-250 mmHg. Two-dimensional grey scale maps of
      axial, lateral and net intrawall displacement components over the full
      pressurization range were generated. Displacement profiles demonstrated
      successful detection of differential radial displacement and good correlation
      with theoretical profiles (root mean square difference 3%). The corresponding
      experimental strain profiles were significantly noisier (root mean square
      difference 76%) due to small fluctuations in the displacement data. This work
      demonstrates that, with further refinement, regional strain mapping in vessel
      walls with intravascular ultrasound imaging is feasible. Mechanical
      characterization of arteries may provide a new tool to aid and treating
      atherosclerotic lesions.

PMID- 9286012
TI  - Chorionicity determination in twin pregnancies: double trouble.

PMID- 9286013
TI  - Monochorionic twin pregnancies: 'les liaisons dangereuses'.

PMID- 9286015
TI  - Abnormal fetal cardiac axis in the detection of intrathoracic anomalies and
      congenital heart disease.
AB  - In a 14-month period, 409 women with singleton gestations referred for perinatal
      ultrasound consultation underwent evaluation of the fetal cardiac axis. Cardiac
      and intrathoracic anomalies were confirmed either by neonatal echocardiography or
      autopsy. Overall, 32 fetuses had an abnormal axis (nine, smaller axis than
      normal; 23, larger axis than normal). Of the 29 found to have cardiac (n = 24) or
      intrathoracic (n = 5) anomalies, 23 had an abnormal axis. The median cardiac axis
      of the normal group (44.0 degrees) was significantly smaller than that of the
      cardiac/intrathoracic anomaly group(60.0 degrees) (p = 0.002). The cardiac axis
      was independent of gestational age. The mean interobserver variation was 1.3 +/-
      1.8 degrees. The sensitivity of an abnormal axis (< 28 degrees or > 59 degrees)
      in detecting congenital heart disease or intrathoracic anomalies was 23/29
      (79.3%), with specificity of 371/380 (97.5%), positive predictive value of 23/32
      (71.9%), and negative predictive value of 371/377 (98.4%). Of those with a
      cardiac anomaly and an abnormal axis (n = 18), five were felt to have an initial
      normal four-chamber view. An abnormal fetal cardiac axis, either larger or
      smaller than normal, is suggestive of a cardiac or intrathoracic anomaly and
      requires further investigation, such as fetal echocardiography. The cardiac axis
      should be considered with the four-chamber view in fetal ultrasound evaluation.

PMID- 9286014
TI  - Increased nuchal translucency thickness at 10-14 weeks of gestation as a
      predictor of severe twin-to-twin transfusion syndrome.
AB  - The study examines a possible association between increased nuchal translucency
      thickness at 10-14 weeks of gestation in monochorionic twin pregnancies and the
      subsequent development of severe twin-to-twin transfusion syndrome (TTS). In 132
      monochorionic twin pregnancies, including 16 that developed severe TTS at 15-22
      weeks of gestation and 116 that did not develop TTS, crown-rump length, nuchal
      translucency thickness and fetal heart rate were measured at 10-14 weeks. In
      those that developed severe TTS, the prevalence of nuchal translucency thickness
      above the 95th centile of the normal range and the intertwin difference in nuchal
      translucency thickness and fetal heart rate were significantly higher than in the
      non-TTS group; there were no significant differences between the groups in the
      inter-twin difference in crown-rump length. For fetal nuchal translucency above
      the 95th centile, the positive and negative predictive values for the development
      of TTS were 38% and 91%, respectively; the likelihood ratios of nuchal
      translucency above or below the 95th centile for the development of severe TTS
      were 4.4 (1.8-9.7) and 0.7 (0.4-0.9), respectively. These findings demonstrate
      that the underlying hemodynamic changes associated with TTS may manifest as
      increased fetal nuchal translucency thickness at 10-14 weeks of gestation.

PMID- 9286016
TI  - Correlation of fetal frontal lobe and transcerebellar diameter measurements: the
      utility of a new prenatal sonographic technique.
AB  - Several authors have reported the value of the sonographic assessment of both the
      fetal frontal lobe and the cerebellum. Both frontal lobe shortening and
      cerebellar hypoplasia have been associated with fetal aneuploidy. We anecdotally
      observed that the distance between the calvarium and the posterior cavum septum
      pellucidum (frontal lobe) closely approximated the transcerebellar diameter. This
      study was undertaken to investigate this relationship. Between 1 July 1994 and 1
      January 1996, the frontal lobe (posterior cavum septum pellucidum to the inner
      calvarium) and transcerebellar diameter were measured in patients referred to two
      prenatal ultrasound laboratories in Denver, Colorado, USA. All pregnancies had
      certain dates and were uncomplicated. Statistical comparison was completed using
      interval polynomial regression analysis. During the study period, we performed
      221 detailed ultrasound examinations in which the frontal lobe and the
      transcerebellar diameter were measured. We found a correlation coefficient of
      0.950 when comparing the two variables (p < 0.0001). Some conditions (Down's
      syndrome, lethal trisomies and pathological microcephaly) have differential
      effects on the frontal lobe and the transcerebellar diameter. Our preliminary
      judgement is that this new technique may prove to be a useful tool in assessing
      the relative effect of these conditions on structural neuroanatomy.

PMID- 9286017
TI  - Amniotic fluid index in twin gestation.
AB  - This study was performed to describe a methodology for a two-pocket amniotic
      fluid index (AFI) for each fetus of a twin gestation. Data included 216 pairs of
      measurements that were analyzed to yield regressions (curves) for all
      observations, as well as for the larger and smaller AFI of each observation on a
      particular set of twins. The twin AFI increased non-linearly until week 27. From
      week 27 to week 36, decreasing linear trends were found. Measures of
      intrasonographer, intersonographer, within-mother and between-mothers variation
      are reported. The estimates of variation were used to plot confidence limits for
      all three curves.

PMID- 9286018
TI  - Echogenic material in the fetal gallbladder and fetal disease.
AB  - The presence of echogenic material within the gallbladder is probably a rare
      finding in the fetus, and the list of predisposing factors known for postnatal
      life seems not to be applicable to prenatal diagnosis. In the present study 1656
      obstetric scans were performed on referrals to the Unit of Fetal Medicine. No
      echogenic gallbladder contents were found before 28 weeks. In the subgroup of 523
      fetuses who were examined during gestational weeks 28-42, six fetuses were found
      to have echogenic material in the gallbladder. The echogenicities were found in
      patients who had the following: extra-amniotic hematoma with intrauterine growth
      retardation and oligohydramnios, tetralogy of Fallot, trisomy 21 with
      atrioventricular septal defect and transient ascites, early abnormally distended
      fetal gallbladder, chromosomal aberration (translocation 10; 11) with bilateral
      clubfoot, and gastroschisis. Echogenic densities had disappeared at ultrasound
      scans performed during early postnatal life in four cases, were absent at five
      weeks in one case, and still present as calculi 8 months after birth in one case.
      Although no causative conclusions can be drawn from the report, these conditions
      are suggested as possible predisposing factors for the presence of echogenic
      material in the fetal gallbladder.

PMID- 9286019
TI  - Doppler velocimetry of the aortic isthmus in human fetuses with abnormal velocity
      waveforms in the umbilical artery.
AB  - Experimental studies in animals using Doppler ultrasound suggest that hemodynamic
      disturbances during fetoplacental circulatory insufficiency will be detected at
      an earlier and less severe stage in the aortic isthmus compared to the umbilical
      artery. In cases in which more severe impairment of the placental circulation was
      achieved, reverse flow was recorded in the aortic isthmus before its appearance
      in the umbilical artery. The present study was undertaken to investigate whether
      the same findings could be demonstrated in the aortic isthmus of the human fetus.
      The video recordings of 100 fetuses with abnormal umbilical artery pulsatility
      index were reviewed. Qualitative abnormalities of the Doppler waveform, i.e.,
      absence or reversal of end-diastolic velocities, were more frequently found in
      the aortic isthmus (absent 28%, reversed 41%) compared to the fetal end of the
      umbilical artery (absent 20%, reversed 19%; p < 0.0001) and also more frequently
      found in the fetal end compared to the placental end (absent 13%, reversed 2%; p
      < 0.0001). This study confirms our previous observations of the aortic isthmus as
      a site for early detection of fetoplacental hemodynamic disturbances. Reverse
      diastolic flow in the isthmus could direct poorly oxygenated blood from the
      descending aorta towards the carotid arteries and the brain. Further prospective
      studies are needed to establish the clinical value of these findings in terms of
      perinatal morbidity and, more importantly, of long-term neurological impairment.

PMID- 9286020
TI  - Reference resistance indices of the umbilical, fetal middle cerebral and uterine
      arteries at 24-42 weeks of gestation.
AB  - The objective of this cross-sectional study was to construct new reference ranges
      for Doppler flow velocity waveform resistance indices for the fetal umbilical
      artery, middle cerebral artery, placental and non-placental uterine arteries and
      the placentocerebral ratio in a large and minimally selected population attending
      a single clinic. Study design and data analysis adhered to a number of stringent
      and validated methodological recommendations derived both from the recent
      literature and from a review of earlier publications in this field. The final
      database comprised initial routine Doppler velocimetry at 24-42 weeks' gestation
      in 1675 pregnancies. Separate regression models were fitted to estimate the mean
      and standard deviation at each gestational age for each vessel. New charts,
      centile tables and regression equations are presented for the resistance indices
      of the fetal umbilical artery, middle cerebral artery, placental and non
      placental uterine arteries and the mean of both uterine arteries and for the
      placentocerebral ratio.

PMID- 9286021
TI  - Saline contrast sonohysterography as first-line investigation for women with
      uterine bleeding.
AB  - The objective of this study was to assess the effectiveness of saline contrast
      sonohysterography (SCSH) as a first-line investigation for perimenopausal women
      with uterine bleeding. A total of 162 women were enrolled in a prospective study.
      They underwent SCSH indicated for abnormal uterine bleeding. Patients with normal
      or atrophic endometrium were scheduled for diagnostic hysteroscopy or hormone
      therapy. Patients with uterine cavity abnormalities were scheduled for surgery
      (operative hysteroscopy or hysterectomy). A clinical follow-up was obtained for
      all the patients after SCSH. Sonohysterographic findings were compared with
      pathological results. SCSH was carried out in 159 patients. In all but one case,
      the procedure was well tolerated by the patients. There were no complications
      either during or after the examination. Surgical and pathological results were
      available in 109 cases. SCSH was highly sensitive and specific in the
      differentiation between women with intrauterine lesions and those with normal or
      atrophic endometrium (98.9% and 76.4%, respectively). SCSH was also accurate in
      the diagnosis of polyps and submucosal myomas (sensitivity 87.8 and 89.6%,
      specifically 90.7 and 95%). SCSH and surgery displayed the same reliability in
      the measurement and the localization of the lesions. SCSH recognized endometrial
      cancer in only 40% of cases. However, all these patients had abnormalities at
      sonohysterography which indicated a surgical exploration, leading to a zero false
      negative rate. Saline contrast sonohysterography appears to be a reliable tool
      for the investigation of abnormal uterine bleeding in perimenopausal women. It
      can distinguish women who only require medical therapy from those who require
      surgery. The method is easy to learn, and is well tolerated by the patients.

PMID- 9286022
TI  - Dilated coronary sinus in the fetus: misinterpretation as an atrioventricular
      canal defect.
AB  - The ostium of the coronary sinus opens directly into the right atrium in close
      proximity to the insertion of the atrioventricular values. If the coronary sinus
      is dilated, it can create the appearance of atrioventricular canal defect in the
      fetal echocardiographic four-chamber view. The diagnosis of a serious heart
      lesion, such as a canal defect, necessitates decisions regarding pregnancy
      termination or optimal timing/location of delivery. We present three women who
      were referred at 23, 36 and 38 weeks' gestation with a preliminary diagnosis by
      level II ultrasound of a fetal atrioventricular canal defect. In each patient,
      the targeted fetal echocardiogram demonstrated a dilated coronary sinus and no
      evidence of an atrioventricular canal defect. The fetal echocardiographic
      presentation of a dilated coronary sinus can be mistaken for an atrioventricular
      canal defect. Misdiagnosis can be avoided by utilizing both variable angulation
      in the four-chamber projection and additional transducer views to confirm an
      intact atrioventricular septum and two normal atrioventricular valves.

PMID- 9286023
TI  - Umbilical cord coagulation by operative microendoscopy at 16 weeks' gestation in
      an acardiac twin.
AB  - Twin reversed arterial perfusion (TRAP) sequence carries high mortality and
      morbidity in the normal twin due to a hemodynamic imbalance through the feto
      fetal vascular anastomosis. This report describes the ultrasound features of TRAP
      in the first trimester and a new technique for selective fetocide in the early
      second trimester in monochorionic twin pregnancies complicated by the TRAP
      sequence. Laser coagulation of the umbilical cord of the acardiac twin was
      performed under sonoendoscopic control. The blood flow in the umbilical cord of
      the acardiac twin was successfully arrested and the survivor developed normally.
      TRAP sequence can be recognized in the first trimester and successfully arrested
      by microendoscopic surgery.

PMID- 9286024
TI  - Prenatal ultrasonographic detection of the tracheal atresia sequence.
AB  - We report a rare case of tracheal atresia, without fistula, in a 19 weeks' female
      fetus. The abnormality was detected by prenatal ultrasonography, which
      demonstrated a bilateral and uniform hyperechogenicity and enlargement of the
      lungs, associated with ascites and moderate oligohydramnios. We suggest that
      oligohydramnios may be helpful in distinguishing the upper respiratory tract
      obstruction from congenital cystic adenomatoid malformation of the lungs, type
      III. A morphometric study revealed a three-fold more dense pulmonary vasculature
      in comparison with two control cases of the same gestational age. The
      pathological finding of pulmonary and vascular hyperplasia as well as the
      pathophysiology of the syndrome are discussed.

PMID- 9286025
TI  - Prenatal diagnosis of ectopia cordis at 10 weeks of gestation using two
      dimensional and three-dimensional ultrasonography.
AB  - We report here the earliest prenatal diagnosis to date of a case of ectopia
      cordis using both two-dimensional and three-dimensional ultrasound at 10 weeks of
      gestation. Both two-dimensional and three-dimensional ultrasound clearly revealed
      a thoracoabdominal ectopia cordis and an omphalocele. Histopathological
      examination confirmed the prenatal ultrasonic findings. In addition to an ectopia
      cordis, a supraumbilical hepato-omphalocele, absence of a pericardium and an
      anterior diaphragmatic defect were seen, although there was a normal sternum.
      These pathological findings, suggested that our case was a variant of pentalogy
      of Cantrell.

PMID- 9286026
TI  - Restrictive dermopathy and associated prenatal ultrasound findings: case report.
AB  - Restrictive dermopathy is a lethal autosomal recessive skin disease. Prenatal
      diagnosis has not yet been reported. We present a case of restrictive demography
      and describe the associated prenatal sonographic findings. A continuously open
      mouth was the most striking feature and this sonographic finding may be a marker
      of a skin disease.

PMID- 9286027
TI  - Cerebro-costo-mandibular syndrome: early sonographic prenatal diagnosis.
AB  - In this case report the sonographic appearance of cerebro-costo-mandibular
      syndrome is described. Increased fetal nuchal translucency (at 11 weeks),
      micrognathia (at 12 weeks) and failure to ultrasound to identify the ribs (at 18
      weeks) were revealed with serial scanning. These cardinal findings allowed the
      prenatal diagnosis of cerebro-costo-mandibular syndrome to be made at 18 weeks'
      gestation.

PMID- 9286028
TI  - Severe twin-to-twin transfusion syndrome: a new sonographic feature of the
      placenta.

PMID- 9286029
TI  - Progress of fundamental research in Wilms' tumor.
AB  - The progress of fundamental research on the histopathological and molecular
      genetic properties, model systems, growth factor involvement, and tumor markers
      of clinical nephroblastoma (Wilms' tumor) are reviewed. Histologically, Wilms'
      tumor (WT) has been found to reveal a disorganized renal developmental process in
      which blastema and epithelia are randomly interspersed in varying amounts of
      stroma. Anaplasia is the only criterion for assigning a WT as having an
      "unfavorable histology." Cytogenetic analysis identified WT genes at chromosome
      11p13 (WT1), 11p15 region (WT2), and 16q (WT3). Permanent in vitro WT cell lines
      and in vivo WT models, such as human xenografts, have been established which
      provide indefinite sources of tumor material for fundamental, as well as therapy
      directed, research. Abnormalities of growth factor (GF) expression in WT indicate
      that GF may play an important role in WT pathogenesis. A series of monoclonal
      antibodies was tested in WT by immunohistochemical techniques to identify
      specific diagnostic and prognostic markers. p53 expression in anaplastic WT is
      significantly higher than in differentiated WTs, indicating p53 may be a
      prognostic marker. Although significant progress has been made in the fundamental
      research, our basic knowledge of this malignancy is still limited. The
      availability of suitable experimental models, particularly the human xenograft
      system, offers the opportunity for further study of the cell biological and
      molecular aspects of WT and its clinical progression.

PMID- 9286030
TI  - Molecular regulation of intercellular adhesion molecule 1 (ICAM-1) expression in
      renal cell carcinoma.
AB  - Intercellular adhesion molecule-1 (ICAM-1) mediates two important functional
      aspects of tumor biology, namely enhancement of tumor metastasis and mediation of
      host defense mechanisms such as lymphocyte-mediated tumor cytotoxicity. Since
      ICAM-1 is expressed by most renal cell carcinomas (RCC), the regulation of ICAM-1
      expression is important in understanding the biological behavior of RCC. We
      report an investigation on ICAM-1 expression and molecular regulation by
      cytokines and protein kinase C activator on RCC cell lines. Of the various
      cytokines, tumor necrosis factor alpha (TNF alpha), interferon-gamma (IFN gamma),
      and phorbol myristate acetate (PMA) strongly upregulated ICAM-1 protein
      expression on RCC. The kinetics of ICAM-1 message induction was studied by
      Northern analysis of total RNA extracted from RCC and normal kidney proximal
      tubular (NKPT) cells. Time course studies showed that ICAM-1 mRNA was upregulated
      by INF gamma, TNF alpha, and PMA, plateaued after 2 h, and remained increased for
      up to 24 h. Although ICAM-1 mRNA in NKPT cells was upregulated by these
      cytokines, their messages returned to basal levels after 24 h. ICAM-1 mRNA
      stability assays showed that both unstimulated and stimulated RCC cells had very
      stable ICAM-1 mRNA up to 24 h. In order to investigate whether increased gene
      transcription contributes to ICAM-1 upregulation, RCC cells were treated with TNF
      alpha, IFN gamma, or PMA with or without simultaneous addition of actinomycin D.
      ICAM-1 message induction-blocking studies suggested that primary upregulation of
      ICAM-1 mRNA may be caused by transcriptional upregulation. These results suggest
      that long-lasting ICAM-1 message upregulation in response to cytokines or PMA may
      be due to transcriptional upregulation in the early phase and stabilization of
      ICAM-1 message in the later phase (after 4 h). These observations suggest that
      RCC may lack the normal downregulatory mechanisms which control ICAM-1 expression
      and may explain the high frequency of ICAM-1 expression observed on primary human
      RCC.

PMID- 9286031
TI  - Cytokine-mediated antitumor effect of OK-432 on urinary bladder tumor cells in
      vitro.
AB  - Fatal complications from the intravesical instillation of bacillus Calmette
      Guerin (BCG) for the treatment of superficial urinary bladder tumors have been
      reported. OK-432, an immunomodulating agent like BCG, may be an effective and
      safe agent for the treatment of urinary bladder tumors. We investigated the
      cytokine-mediated antitumor effect of OK-432 on established human bladder cancer
      cell lines (T24 and KK-47) in vitro. Peripheral blood mononuclear cells (PBMCs)
      from a healthy volunteer were cultured with OK-432 for various periods, and the
      culture supernatants were used as conditioned media. Cytokines in the culture
      supernatants were quantified. The antitumor effect of OK-432 was evaluated by
      colony-forming assays, using the conditioned media as the culture media. The
      colony survival of T24 and KK-47 cells was significantly inhibited by conditioned
      media from 24-h cultures of PBMCs incubated with OK-432 at concentrations of 0.05
      and 0.1 Klinische Einheit (KE)/ml. Conditioned media from PBMCs cultivated with
      OK-432 for 7 days at 0.01 and 0.05 KE/ml also significantly inhibited the colony
      survival of both cell lines. Higher concentrations of interleukin-1 beta (IL-1
      beta) and tumor necrosis factor alpha (TNF alpha) were detected in conditioned
      media cultivated with OK-432 for 24 h than in media from PBMCs alone. However,
      higher concentrations of interferon gamma (IFN gamma) were detected in
      conditioned media cultivated with OK-432 for 7 days. Approximately 90% of the
      inhibition of KK-47 cells by the 24-h conditioned media was neutralized by an
      anti-TNF monoclonal antibody. The inhibition of T24 cells was neutralized
      approximately 50% by the same antibody. The inhibition of T24 and KK-47 cells by
      7-day conditioned media was completely neutralized by an anti-IFN gamma
      monoclonal antibody. The cultivation of PBMCs with OK-432 inhibited the
      production of granulocyte-colony-stimulating factor (G-CSF) by PBMCs. The
      inhibition may play a role in the mechanism of the antitumor effect of OK-432.
      Urinary bladder tumor cell lines have different sensitivities to cytokines. The
      cytokines induced by OK-432 vary with the concentration of OK-432 and the culture
      period. It is suggested that in intravesical instillation of OK-432 for treatment
      of urinary bladder tumor, the optimal dose and interval of instillation should be
      considered.

PMID- 9286032
TI  - In vitro investigations of new therapeutic agents on bladder tumor cell lines.
AB  - In this study sensitivity of human transitional cancer cells to the anticancer
      agent paclitaxel, an antimicrotubular drug, and to gallium nitrate, a group IIIa
      metal, was compared to that of the standard MVAC (methotrexate, vinblastine,
      doxorubicin and cisplatin) drugs. The reduction of cell proliferation was
      evaluated after 48 h of incubation of six different cell lines with each agent
      using the mean transit time (MTT) assay. We investigated both monolayers and
      spheroids. Paclitaxel showed significantly higher growth inhibitory effects on
      monolayers than vinblastine, both agents targeting the antimicrotubular
      apparatus. This could not be reproduced on spheroids, where a survival fraction
      of 50% was observed even at high concentrations (10 microM). High concentrations
      of gallium nitrate were needed to achieve sufficient toxicity. These
      concentrations are beyond the concentration achievable by systemic application.
      Our findings suggest that paclitaxel may be a clinically useful agent for
      systemic and intravesical use in bladder cancer.

PMID- 9286033
TI  - Beta-galactosidase as a marker of HSP70 promoter induction in Dunning R3327
      prostate carcinoma cells.
AB  - Hyperthermia is known to improve the response of tumors to radiation or
      chemotherapeutic treatment when combined in multimodal strategies. The cellular
      response to hyperthermia is associated with the synthesis of heat shock proteins
      (HSP). To study the stress response in prostate cancer we have developed a clone
      of Dunning R3327 rat prostate carcinoma cells stably transfected with a gene
      construct containing the E. coli beta-galactosidase gene driven by the Drosophila
      HSP70 promoter. The measurement of beta-galactosidase serves as a rapid and
      semiquantitative assay of HSP70 gene activation. The Dunning cell clone showed
      evidence of incorporation of the HSP70/beta-galactosidase construct within the
      genomic DNA by Southern blot analysis. When compared to mock-transfected control
      cells, the clone showed minimal baseline beta-galactosidase activity, which
      significantly increased following a hyperthermic stress. The time course of beta
      galactosidase elevation following heat stress paralleled the time course of
      cellular HSP70 elevation by Western blot analysis. These stably transfected
      Dunning R3327 cells may provide a useful tool to study the effects of
      hyperthermia, radiation, and chemotherapeutic agents on the cellular stress
      response and in the establishment of HSP70 as a marker of cellular resistance in
      the multimodal treatment of prostate cancer.

PMID- 9286034
TI  - Morphological correlates of urinary enzyme loss after extracorporeal lithotripsy.
AB  - Urinary loss of the tubular marker enzyme N-acetyl-beta-D-glucosaminidase (NAG)
      immediately following extracorporeal lithotripsy suggests corresponding
      morphological changes in the kidney. To date, the morphological correlate of the
      enzymuria remains unclear. In this animal study with Wistar rats acute
      morphological changes in the tubulus cells beneath isolated tubulus necrosis were
      demonstrated. The mechanically induced lesions of the cell organelles included
      fragmentation of the lysosomes and severe alterations of the cell membrane. The
      tubulus damage was quantified. With the help of histochemical NAG staining and
      electron microscopic observations, a significant correlation between number and
      intensity of shock waves and tubular damage was found. The intracellular lesions
      described here are at least part of the morphological basis of shock-wave-induced
      enzymuria. The results show that enzymatic changes in urine reflect visible renal
      damage.

PMID- 9286035
TI  - Urease-induced crystallizations of calcium phosphate and magnesium ammonium
      phosphate in synthetic urine and human urine.
AB  - An aggregometer technique was used to study urease-induced crystallizations in
      synthetic urine and human urine from healthy subjects and patients with chronic
      spinal cord injuries. The two different phases of crystallization, calcium
      phosphate and magnesium ammonium phosphate, were easily evaluated with a single
      assay using this technique. The crystallization of calcium phosphate and
      magnesium ammonium phosphate varied markedly among the different urine specimens
      after incubation with urease. The turbidity curves from human urine were divided
      into four patterns. We assumed that the variations in the patterns of the
      turbidity curves appeared to be mainly due to differences in the composition of
      the urine and in the original pH, and that the calcium and magnesium
      concentrations were very important in the urinary constituents.

PMID- 9286036
TI  - An in vitro study of nonadrenergic-noncholinergic activity on the cavernous
      tissue of mouse.
AB  - The relaxant effects of electrical field stimulation (EFS) and exogenously
      applied acetylcholine (ACh) or acidified NaNO2 (a-NaNO2) were investigated in the
      isolated mouse corpus cavernosum precontracted with phenylephrine hydrochloride
      (PE). Tetrodotoxin (TTX) blocked the relaxant effects of EFS completely, whereas
      it had no effect on the responses to ACh or a-NaNO2. Guanethidine and
      indomethacin failed to affect the electrically or ACh-induced relaxations.
      Atropine completely blocked the effect of ACh; however, it caused a slight
      reduction in the relaxation evoked by EFS. NG-Nitro-L-arginine (L-NOARG) reduced
      the effects of EFS and ACh significantly, but it was ineffective on the
      relaxations induced by a-NaNO2. The inhibitory action of L-NOARG was partly
      restored by L-arginine, but not by D-arginine. Methylene blue (MB) and
      hydroxocobalamin (HC) exhibited significant inhibition on the relaxations evoked
      by EFS, ACh and a-NaNO2. Hydroquinone (HQ) reduced relaxation due to a-NaNO2, but
      did not affect that of EFS and ACh. Our findings suggest that EFS-induced
      relaxations of mouse cavernosal tissue are mediated by a transmitter which
      probably resembles an organic nitrate.

PMID- 9286037
TI  - Cellular localization of immunoreactive epidermal growth factor during Wolffian
      duct differentiation of the fetal mouse.
AB  - Previous studies from this laboratory indicated a role for epidermal growth
      factor (EGF) in androgen-dependent male reproductive tract differentiation of the
      fetal mouse. Expression of an EGF-like protein during Wolffian duct
      differentiation was indicated from the determinations by radioimmunoassay (RIA)
      and radioreceptor assay. To further characterize the protein and to assess its
      role in male sexual differentiation, expression of the protein has been analyzed
      by Western blot assay and its tissue-specific cellular expression has been
      determined by immunocytochemical assay in the present study. Western blot
      analysis of the 18-day fetal male reproductive tract detected an immunoreactive
      band of the predicted 6-kDa size. Immunocytochemical analysis also detected EGF
      specific immunostaining in the Wolffian duct derivatives. At day 18 of gestation,
      the staining was localized predominantly in the epithelial nuclei of the Wolffian
      duct derivatives whereas at days 14 and 16 of gestation, the staining was equally
      distributed in the mesenchymal and epithelial sites of the Wolffian duct
      derivative. The intensity of the staining increased with progression of
      differentiation during the 14th-18th days of gestation. Prenatal exposure to the
      antiandrogen flutamide significantly reduced the immunostaining of the duct.
      Thus, a role for EGF in Wolffian duct differentiation is indicated.

PMID- 9286038
TI  - Fixation of human detrusor smooth muscle cells: role of osmolarity and magnesium
      ions on the ultrastructural morphology.
AB  - Magnesium ions added to fixatives for processing to Transmission Electron
      Microscopy (TEM) have been claimed to cause relaxation of detrusor smooth muscle
      cells [1]. This should facilitate the morphologic evaluation of the tissue.
      However, magnesium ions are osmotically active and their addition may cause the
      fixative to become hypertonic to the tissue. To ascertain whether the presence of
      magnesium ions causes significant changes compared to those found where the
      osmolarity is raised without the presence of magnesium, human detrusor specimens
      were fixed in glutaraldehyde to which increasing amounts of MgCl2 or NaCl were
      added in different concentrations. With the addition of increasing amounts of
      MgCl2 and NaCl, the osmolarity of the fixative increased, causing significant
      changes in the morphology and morphometry of the tissue. The intercellular
      distances increased, the cells shrank and the shape of the cells changed from
      smooth and rounded to spiky and angulated. With regard to its muscle-relaxing
      effect, it was not possible to distinguish the specimens fixed in magnesium
      containing fixatives from those without. In this study it was not possible to
      prove any relaxing effect of magnesium ions added to the fixative. On the
      contrary the magnesium ions caused an increase in the osmolarity, with
      significant changes in both the morphometry and the morphology of the human
      detrusor smooth muscle cells.

PMID- 9286039
TI  - Ability of obstructed bladders to empty is dependent on method of stimulation.
AB  - PURPOSE: To correlate pharmacologic changes that occur in the bladder after a
      partial outlet obstruction with the bladder's ability to perform work and empty.
      METHODS: After 2 weeks of partial outlet obstruction, rabbit bladders were
      stimulated in vitro both isovolumetrically [field stimulation (FS)] and to empty
      (FS, bethanechol, and KCl). RESULTS: The obstructed bladders were separated into
      two groups according to their ability to empty when stimulated with FS.
      Compensated bladders were those that could empty as much as controls.
      Decompensated bladders emptied significantly less than controls. With FS and
      bethanechol, the compensated obstructed bladders showed no difference from the
      control bladders in their ability to empty. In contrast, with KCl, the
      compensated bladders generated significantly less pressure, performed less work,
      and emptied less than controls. When the decompensated bladders were stimulated
      with all three types of stimulation, all parameters, including emptying ability,
      were significantly decreased. CONCLUSIONS: The reduction in the response of
      compensated bladders to KCl stimulation suggested that the initial defects to the
      bladder after an outlet obstruction involved the interaction of smooth muscle
      proteins with calcium and ATP. In contrast, the response of decompensated
      bladders to all three forms of stimulation was equally reduced, suggesting that
      the degenerative processes were directly related to significant cellular damage
      to metabolic processes involved in energy synthesis, storage, and utilization.

PMID- 9286040
TI  - Vaccinator device for delivering propellant-driven aerosols of Streptococcus suis
      bacterin into the respiratory tracts of swine.
AB  - Metered-dose propellant-driven small particle aerosols of a killed whole
      bacterium, Streptococcus suis, were produced and characterized for their
      aerodynamic particle sizes and antigenicity as potential respiratory mucosal
      vaccines against S. suis infections in swine. To facilitate the efficient
      delivery of such vaccine aerosols to large animals, an electro-mechanical device
      was developed to synchronize aerosol release to an animal's inhalation cycles.
      The device was tested for its capacity to deliver a fluorescein conjugate of this
      bacterin (FITC-S. suis) into the respiratory tracts of 18 pigs. Results showed
      that FITC-S. suis could be detected in the lungs of swine as small as 4.5 kg with
      as few as two aerosol actuations. Metered-dose propellant-driven aerosols of
      bacterin vaccines delivered by this respiratory vaccinating device are discussed
      as a new approach for stimulated mucosal immunity against respiratory infections
      in animals.

PMID- 9286041
TI  - Synthesis of alpha-gal epitopes on influenza virus vaccines, by recombinant alpha
      1,3galactosyltransferase, enables the formation of immune complexes with the
      natural anti-Gal antibody.
AB  - Synthesis of the carbohydrate structure Gal alpha 1-3Gal beta 1-4GlcNAc-R (termed
      the alpha-gal epitope) on viral glycoproteins is of interest because of the large
      amounts of natural antibody (anti-Gal) produced in humans against this epitope.
      The presence of alpha-gal epitopes on inactivated virus or subviral vaccines is
      likely to enhance vaccine immunogenicity through in vivo complexing with anti-Gal
      and the subsequent targeting of the vaccine to Fcy receptors on antigen
      presenting cells. Our previous studies have demonstrated the increased in vitro
      immunogenicity of inactivated influenza virus complexed with the anti-Gal
      antibody. Here we demonstrate a method for engineering the expression of alpha
      gal epitopes on influenza virus hemagglutinin (HA) by recombinant alpha
      1,3galactosyltransferase (r alpha 1,3GT). We further demonstrate the formation of
      immune complexes between this de novo synthesized epitope and anti-Gal. HA has
      multiple N-acetyllactosamine structures which serve as excellent acceptors for r
      alpha 1,3GT. The luminal portion of marmoset alpha 1,3GT cDNA was produced in
      large amounts in the baculo virus system and isolated by affinity chromatography
      on nickel-Sepharose columns. r alpha 1,3GT effectively transferred galactose from
      UDP-Gal to the N-acetyllactosamine residues of HA on the intact virion or to
      isolated HA molecules. At least 3000 alpha-gal epitopes were de novo synthesized
      per virion. The natural anti-Gal antibody bound to these epitopes in ELISA, in
      western blots and in solution, forming distinct immune complexes. These data
      suggest that in vivo administration of such vaccines will result in their
      complexing with anti-Gal, and thus may lead to their increased immunogenicity.

PMID- 9286042
TI  - Mechanisms of adjuvancy: I--Metal oxides as adjuvants.
AB  - The exact mechanism of how immune adjuvants function still remains largely
      unknown, despite their long history of use. This work reports the properties of
      alum and the related compounds Al(OH)3 or Al2O3. Experiments were performed in
      rats to determine the relative adjuvancy of silica, talc, ground glass, Al2O3,
      SnO2, ZrO2, hematite and magnetite. Antibody response and cell-mediated immunity
      (CMI) to ovalbumin (OVA) were determined and were found to be significantly
      enhanced by silica and talc. Antibody response to OVA was moderately enhanced by
      Al2O3, hematite, and magnetite, while CMI to OVA was not affected, SnO2, ZrO2,
      and ground glass only gave a slight adjuvant effect. The magnitude of adjuvancy
      appeared to correlate with the magnitude of the inflammatory response produced by
      each metal oxide and also correlated with their surface area. No correlation
      could be drawn between the hydrophilicity or hydrophobicity of the metal oxides
      and the magnitude of their adjuvancy.

PMID- 9286044
TI  - Broadly reactive antibodies against a gp120 V3 loop multi-epitope polypeptide
      neutralize different isolates of human immunodeficiency virus type 1 (HIV-1).
AB  - A gene encoding for a novel multi-epitope polypeptide (TAB4) was synthesized and
      expressed in Escherichia coli. The protein was composed of 15 amino acid
      fragments derived from the V3 loop of HIV-1 isolates MN, IIIB, RF, JY1, BRVA and
      LR150, joined by five-amino-acid linkers. Immunogenicity of TAB4 in rabbits was
      studied, and the antibody response against individual peptides investigated. TAB4
      was shown to be immunogenic in Complete Freund's Adjuvant in a dose-dependent
      manner, and was able to elicit a humoral response against all V3 epitopes
      included on the protein. Sera from some of the animals were able to neutralize
      the replication of viral strain MN, and in one case IIIB, with moderate titers.
      Some sera also neutralized several Cuban clinical strains, isolated in peripheral
      blood mononuclear cells, after one round of amplification in MT4 cells.

PMID- 9286045
TI  - Immunogenicity and protectivity of a new liposomal hepatitis A vaccine.
AB  - In this study we investigated a new liposomal hepatitis A vaccine (Epaxal)
      developed by the Swiss Serum and Vaccine Institute clinically and immunologically
      using a one dose priming schedule and a booster injection after 1 year. This
      vaccine contains formalin inactivated hepatitis A virus particles attached to
      phospholipid vesicles together with influenza virus haemagglutinin. Two doses of
      the vaccine were administered at months 0 and 12 in 117 volunteers. Blood samples
      were drawn at days-7, 14 and 28 and after 6, 12 and 13 months, local and systemic
      reactions were monitored by means of questionnaires. Immunogenicity was evaluated
      as usual by the determination of anti-HAV from the collected sera using the ELISA
      technique. In order to evaluate the protective efficacy of the vaccine induced
      antibodies a sample of 25 sera mainly from vaccinees showing low ELISA titres was
      additionally analysed by means of a virus NT. The vaccine was excellently
      tolerable and highly immunogenic. Seroconversion evaluated by ELISA was 97 and
      99%, respectively, 14 and 28 days after the first dose and 100% after the second
      dose. NT titres were well correlated with ELISA titres and showed similar
      seroconversion rates even in the early phase of immunization. The results of this
      study show that with two doses of the liposomal hepatitis A vaccine administered
      at months 0 and 12 early protection within 14 days and long lasting immunity can
      be achieved.

PMID- 9286046
TI  - Inhibition of multiplication of Mycobacterium leprae in mouse foot pads by
      immunization with ribosomal fraction and culture filtrate from Mycobacterium
      bovis BCG.
AB  - Immunization of mice with the ribosomal fraction from ruptured Mycobacterium
      bovis Bacillus Calmette-Guerin (BCG) and the culture filtrate reduced remarkably
      the multiplication of Mycobacterium leprae in the foot pads of mice. This is the
      first reported case of the protective activity against M. leprae multiplication
      in mice of the BCG ribosomal fraction and culture filtrate. The inhibition was
      more evident with the culture filtrate than with the ribosomal fraction. When the
      ribosomal proteins separated from ribosomal RNA were injected into mice, only
      slight inhibition was observed. Ribosomal RNA alone did not inhibit at all, in
      contrast to the conclusion reported by Youmans and Youmans.

PMID- 9286047
TI  - Acellular pertussis vaccines containing genetically detoxified pertussis toxin
      induce long-lasting humoral and cellular responses in adults.
AB  - New generation pertussis vaccines, containing only purified Bordetella pertussis
      antigens, have been proven safe, immunogenic and efficacious. They have, however,
      raised new questions regarding the mechanism of protection from whooping cough
      and the duration of the immune response following vaccination. In addition to the
      antibody (Ab) titer, the level of pertussis toxin (PT) neutralizing antibodies
      may be very important in protection and the role of cell-ediated immunity needs
      to be defined. We have previously reported the safety and immunogenicity results
      of two phase I trials in adult volunteers with two acellular pertussis vaccines
      containing genetically detoxified PT alone or in combination with filamentous
      hemagglutinin (FHA) and 69K protein. In this work, we present the results of a
      long term follow-up study of the immune response in the same vaccinees. We
      evaluated the Ab response, the PT neutralizing titer and the peripheral blood T
      cell response up to 4 years following vaccination. Our results show that in
      adults the level of antibodies to PT, FHA and 69K and the PT neutralizing titers
      slightly decline between 2.5 and 12 months after the last vaccine dose, but they
      remain high in the following 2-4 years, showing levels 10-100 times higher than
      pre-vaccination values. The T cell responses were more heterogeneous among
      vaccinees but they did not show any significant decline throughout the period
      monitored.

PMID- 9286048
TI  - Outer membrane vesicle vaccines made from short-chain lipopolysaccharide mutants
      of serogroup B Neisseria meningitidis: effect of the carbohydrate chain length on
      the immune response.
AB  - Outer membrane vesicle (OMV) vaccines were made from Neisseria meningitidis
      strain 44/76 and its two short-chain lipopolysaccharide (LPS) mutants, Mu-1 and
      Mu-4. Only the 44/76 vaccine contained LPS with the host antigen lacto-N
      neotetraose. The protein composition of the vaccines was similar. The LPS
      carbohydrate chain length proved to influence drastic changes in the LPS
      immunogenicity as well as the outer membrane proteins (OMPs) ability to elicit
      functional antibodies in mice. Only LPS in the Mu-1 and Mu-4 vaccines were
      immunogenic, and the 44/76 vaccine differed also by not inducing antibodies to
      the class 4 OMP. The Mu-1 vaccine, with a LPS carbohydrate chain comprising only
      two residues of 2-keto-3-deoxy-octonic acid, induced lower bactericidal activity
      and less antibodies to the class 1 OMP, compared to the two other vaccines. This
      indicates that LPS of a certain carbohydrate chain length is required for
      adequate exposure of the class 1 OMP epitopes essential for inducing bactericidal
      antibodies.

PMID- 9286049
TI  - Acellular pertussis vaccine in children with perinatal human immunodeficiency
      virus-type 1 infection.
AB  - The immunogenicity of an acellular pertussis vaccine containing genetically
      detoxified pertussis toxin, filamentous haemoagglutinin and pertactin was studied
      in 12 children [median age: 45 (6-107) months] with perinatal human
      immunodeficiency virus-type 1 (HIV-1) infection. Antibody response to all
      antigens was observed in six cases and another children 3 reacted to two or one
      antigen(s), but titres were lower than those from healthy controls. Antibody
      titre fold-rise correlated with preimmunization CD4-positive cell counts.
      Significant titres were still detectable 4 months after the third dose. The
      acellular vaccine is immunogenic in a portion of children with perinatal HIV-1
      infection but early vaccination might be more effective, taking advantage of
      still adequate CD4-positive cell numbers.

PMID- 9286050
TI  - Allergic mucocutaneous reactions to Japanese encephalitis vaccine.
AB  - Japanese encephalitis (JE) vaccine has been used in childhood immunization
      programmes in Asia for many years. Also travellers from other parts of the world
      have been vaccinated before travelling in Asian countries. Recommendations for
      the use of JE vaccine are still debated because severe cases of adverse reactions
      have been reported. In Denmark an inactivated JE vaccine derived from infected
      mouse brain has been used and 350000 doses have been distributed from the Statens
      Serum Institut since 1983. In the period 1983-1995, 101 adverse reactions after
      JE vaccination have been registered including 73 allergic mucocutaneous
      reactions. These reactions have occurred each year since 1989 with frequencies
      varying from 1-17 per 10,000 vaccinees. The highest frequencies and the most
      serious reactions acquiring hospitalization were seen in the period 1989-1992.
      Three batches (EJN 012, 033 and 048) distributed before 1992 caused the highest
      number of reactions but all batches delivered in Denmark since 1989 have caused
      reactions. Therefore, it is still very important to collect information on
      adverse events as well as information of the risk of acquiring JE infection in
      order to give sound recommendations to travellers.

PMID- 9286051
TI  - Nasal immunization with group B streptococci can induce high levels of specific
      IgA antibodies in cervicovaginal secretions of mice.
AB  - We have studied the cervicovaginal antibody responses in mice, by ELISA,
      following mucosal immunizations with group B streptococci (GBS) serotype III/R4.
      Immunizations were carried out either: (1) rectally with GBS alone; (2) rectally
      with GBS plus cholera toxin (CT); (3) nasally with GBS alone; (4) nasally with
      GBS+CT; or (5) nasally under general anesthesia with GBS+CT. Nasal immunizations
      with GBS alone led to at least tenfold higher levels of specific IgA-antibodies
      to GBS in cervicovaginal secretions than with any other immunization. These
      mucosal antibody levels were higher than after rectal immunizations, and 2-17
      times higher than the corresponding IgA antibody levels in sera. Markedly lower
      cervicovaginal antibody levels were found in mice which had received GBS together
      with CT as a mucosal adjuvant than in mice immunized by the same routes with GBS
      alone. Our observations indicate that a nasal vaccine consisting of GBS might
      induce sufficient antibody levels to protect against genital colonization of
      these bacteria.

PMID- 9286052
TI  - Hepatitis A vaccine: persistence of antibodies 5 years after the first
      vaccination.
AB  - The recent development of safe and effective inactivated hepatitis A vaccines
      provides the opportunity to control hepatitis A. However, effective control will
      depend upon the duration of protection provided by the vaccine. Evaluation of
      persistence of antibodies over time is essential for the determination of
      vaccination schedules and strategies. For this purpose blood samples were
      obtained from 140 volunteers, 5 years after the administration of three 720 ELISA
      units (EU) doses of an inactivated hepatitis A vaccine according to a 0, 1 and 6
      month schedule. All serum samples were tested for anti-hepatitis A virus (HAV)
      antibodies using a sensitive ELISA inhibition assay. All subjects, except one,
      had anti-HAV titres > or = 20 mIU ml-1. The geometric mean titre (GMT) was 1258
      mIU ml-1. All individual titres were at least 10 times higher than the minimum
      protective level. According to the rate of antibody level decrease over time, the
      predicted duration of antibodies is estimated to be at least 20 years.

PMID- 9286053
TI  - Protection, humoral and cell-mediated immune responses in calves immunized with
      multiple emulsion haemorrhagic septicaemia vaccine.
AB  - A multiple emulsion (ME), vaccine against Pasteurella multocida (P52) infection
      in cattle was prepared and the efficiency in terms of immunity to direct
      challenge, duration of this immunity for up to 1 year and the role of humoral and
      cell-mediated immune mechanisms were studied. ME vaccine was sterile, safe and
      was potent when tested in rabbits and calves. Nineteen calves were immunized with
      a single 4 ml dose of ME vaccine intramuscularly. Group of these calves were
      challenge infected with virulent P. multocida (P52) (10(-1) 18 h old broth
      culture) given by the subcutaneous route at 21 days, 3 months, 6 months, 9 months
      and 1 year. All the immunized calves withstood challenge infection and showed
      100% protection. Humoral immune response was measured by indirect
      haemagglutination test (IHA) and enzyme-linked immunosorbant assay (ELISA).
      Statistically ELISA values were found to be superior to IHA values because of
      small coefficient of variance. A fall in mean antibody titres during 24 h, 48 h,
      post-challenge infection was recorded whereas a steady increase in the titre
      after 72 h up to 10 days was noticed. The prechallenge mean titre in animals
      correlated with survival of animals. Humoral antibodies were detected as early as
      7 day post-immunization and persisted to 1 year after immunization. Leucocyte
      migration inhibition test showed > 20% migration inhibition during all pre- and
      post-challenge periods in animals suggesting an involvement of cell-mediated
      immune mechanism in protection. Our findings suggested that both humoral and cell
      mediated immune responses contribute to protection in vaccinated animals. The
      results of these studies of ME vaccine showed that it can be successfully used
      for the effective control of haemorrhagic septicaemia.

PMID- 9286054
TI  - Generation of bovine immune colostrum against Streptococcus mutans and
      Streptococcus sobrinus and its effect on glucose uptake and extracellular
      polysaccharide formation by mutans streptococci.
AB  - Due to potential side-effects of active immunization by cariogenic mutans
      streptococci, oral administration of passively-derived antibodies could be a more
      acceptable way to reduce colonization and virulence of these microorganisms in
      human dentition. The aim of this study was to produce antistreptococcal
      immunoglobulins into bovine colostrum and explore the possible antibacterial
      mechanisms of these immunoglobulins against mutans streptococci. Specific serum
      IgG antibodies to whole cell antigens of both Streptococcus mutans and
      Streptococcus sobrinus increased rapidly in cows during immunization and were
      high also in the final whey-product. Low concentration (0.5% w/v) of bovine
      immune preparation inhibited significantly the incorporation of [14C]glucose by
      both S. mutans and S. sobrinus. Higher concentration (> 1%) was needed to inhibit
      the glucosyltransferase or fructosyltransferase activities of these bacteria. No
      such inhibitory effects were observed with the control preparation from the non
      immunized cows. Our results indicate that bovine immune colostrum has a
      significant inhibitory potential against mutans streptococci, apparently
      dependent on the presence of specific IgG antibodies against S. mutans and S.
      sobrinus.

PMID- 9286055
TI  - Simian immunodeficiency virus (SIV)-specific CD8+ cytotoxic T lymphocyte
      responses of naive and vaccinated cynomolgus macaques infected with
      SIVmac32H(J5): quantitative analysis by in vitro antigenic stimulation.
AB  - Detailed analyses of simian immunodeficiency virus (SIV)-specific cytotoxic T
      lymphocyte (CTL) responses in vaccinated and infected macaques may help to
      clarify the role of CTL immunity in protection against lentiviruses. Here, the
      optimal conditions for the measurement of SIV Gag-specific CTL were investigated
      by bulk and limiting dilution assays of peripheral blood mononuclear cells (PBMC)
      from naive and vaccinated cynomolgus macaques (Macaca fascicularis) infected with
      SIVmac32H(J5). In vitro restimulation was generally required for CTL detection.
      Selective activation of CD8+ and MHC-restricted SIV Gag-specific CTL was induced
      by stimulation with autologous para-formaldehyde-fixed B-lymphoblastoid cell
      lines infected with a recombinant vaccinia virus expressing SIV Gag. Applied to
      limiting dilution assays, antigenic stimulation reproducibly demonstrated SIV Gag
      specific CTL precursors (CTLp) in PBMC of all animals studied, including those
      lacking significant responses in standard bulk CTL assays.

PMID- 9286056
TI  - Immunogenicity of filamentous phage displaying peptide mimotopes after oral
      administration.
AB  - Selected human sera can be used to identify disease-related peptide epitopes
      (mimotopes) displayed on bacteriophages. Parenteral administration of such
      recombinant phages is an effective route of immunization in different
      experimental animals, indicating that mimotopes could be an important source of
      leads for new vaccines. Here it is shown that intranasal or intragastric
      administration of phage in mice induces an immunological response both to the
      wild type proteins of the phage and to mimotopes displayed on them. Using
      mimotopes of human HBV surface antigen and of human HCV peptides, the authors
      show that the response induced by oral administration is specifically cross
      reactive with the original antigen. These findings indicate that phage displaying
      selected mimotopes could be useful for the development of orally effective
      vaccines.

PMID- 9286057
TI  - Mycoplasmas: agents of human, animal, and plant infections.

PMID- 9286058
TI  - Comparative genomics of mycoplasmas.
AB  - The mycoplasmas are the smallest and simplest self-replicating organisms. The
      goal of defining in molecular terms the entire machinery of a living cell by
      using mycoplasmas as models was put forward by Harold Morowitz in 1984. The
      recent complete sequencing of the genomes of the human pathogens Mycoplasma
      genitalium and Mycoplasma pneumoniae brings us much closer to achieving this
      goal. The M. genitalium genome contains only 479 predicted protein coding
      sequences (genes) and that of M. pneumoniae 677, as compared with 1703 in
      Haemophilus influenzae and about 4000 in E. coli. Thus, M. genitalium is
      apparently the simplest organism capable of independent life with a minimal set
      of genes. The drastic economization in genetic information must have been
      associated with the parasitic mode of life of the mycoplasmas. During their
      reductive evolution from Gram-positive bacteria the mycoplasmas have lost the
      cell wall and many biosynthetic systems involved in synthesis of macromolecule
      building blocks provided by their host. Thus, the M. genitalium and M. pneumoniae
      genomes do not carry any gene involved in amino acid biosynthesis, and very few
      genes for vitamin, nucleic acid precursor and fatty acid biosynthesis. The
      mycoplasma genomes carry a minimal set of energy metabolism genes, being content
      with a restricted supply of ATP needed for their parasitic mode of life.
      Nevertheless, these minimal organisms carry the essential genes for DNA
      replication, transcription and translation, but even here gene saving is
      expressed by a minimal number of rRNA and tRNA genes. A genomic price had been
      paid to maintain parasitism, so that a significant number of mycoplasmal genes is
      devoted to adhesins, attachment organelles and variable membrane surface antigens
      directed towards evasion of the host immune system.

PMID- 9286059
TI  - Molecular biology of Mycoplasma.
AB  - Mycoplasmas are the smallest free living microorganisms with the smallest genome.
      The G+C content is in general low (25-33%) and the coding capacity is about 600
      proteins. Mycoplasma species are phylogenetically related, they use the genetic
      codon UGA for tryptophan, and show rapid evolution, with a high rate of
      divergence. The genomes of Mycoplasma genitalium and Mycoplasma pneumoniae have
      been fully sequenced. Striking features of the M. genitalium sequencing project
      are the presence of a high number of membrane proteins with no resemblance to
      previously sequenced genes and the presence of repeated fragments of the gene
      encoding the tip-localized 140 kDa adhesin (MgPa). Many Mycoplasma species
      display a high frequency of antigenic variation, both as phase and size variation
      of individual antigens. Mycoplasma hominis isolates are known to be antigenic
      heterogeneous, as reflected in the reactivity with monoclonal antibodies (MAbs).
      The genetics of the antigenic variation has been studied for three different
      surface exposed antigens: P120, Lmp, and P50/Vaa. The gene encoding P120 had a
      hyper-variable region in the N-terminal region. In addition, a second gene with
      homology to p120 was identified. The gene encoding Lmp, a 135 kDa protein is
      repeated and both genes are translated and both contain internal repeated
      sequences. Deletion mutants in the lmp gene were obtained by cultivation of M.
      hominis PG21 with MAb 552 specific for the repeated part of Lmp. One of the lmp
      genes had deletions of from four to eight repeats. The other gene was left
      unaltered. The genes encoding P50/Vaa show a different form of variability where
      domains of the genes seem to be exchangeable. The genomic maps of five M. hominis
      strains showed that even though the size of the genomes varied the position of
      the different genes were in general conserved.

PMID- 9286060
TI  - Mycoplasma genetic variation and its implication for pathogenesis.
AB  - Several pathogenic mycoplasma species are known etiologic agents of diseases in
      man and animals, which typically involve the respiratory tract, urogenital tract
      and joints and often show chronicity. Although the basis for this chronicity is
      not well understood, it is apparent that several species of pathogenic
      mycoplasmas are endowed with a sophisticated genetic machinery for altering their
      surface attributes. This surface phenotypic variation is thought to play a key
      role in the establishment and persistence of mycoplasma infections by enabling
      evasion of host defences and by ensuring adaptation to the rapidly changing
      microenvironmental conditions encountered in the host. The variability of
      mycoplasma surface characteristics results both from reversible ON- and OFF
      switching of distinct membrane surface proteins (phase variation), from
      structural changes of these proteins (size variation) and from changes in their
      surface presentation (epitope masking and demasking). The majority of these
      surface proteins that are subject to variation are encoded by multiple variant
      single-copy genes and are lipid-modified proteins which represent the major coat
      proteins and surface antigens of several pathogenic mycoplasmas. Variable surface
      lipoproteins play an important role in the pathogenesis of a mycoplasma infection
      by providing escape from immune response, and probably by influencing both
      colonization of and translocation across the mucosal barrier. In this minireview,
      recent developments regarding the genetic mechanisms and the functional
      significance of surface lipoprotein variation in the pathogenesis of mycoplasma
      infections are summarized.

PMID- 9286061
TI  - Models of mycoplasma respiratory and genital tract infections.
AB  - Animal models for the study of human diseases must be replaced by in vitro
      methods, whenever possible. However, when critically evaluated, they remain
      indispensable for the solution of some specific problems in infectious diseases.
      These include the pathogenesis, the host response, as well as the study of
      antimicrobial agents and vaccines. Under these conditions animal models, which
      closely reflect the situation in man, are especially valuable. Two models may
      serve as "ideal" examples for the study of human diseases: firstly mouse typhoid
      for the study of systemic infections with Salmonella typhimurium. This model has
      been employed for many decades to examine various aspects of human typhoid fever.
      A second model is the experimental infection of hamsters with Mycoplasma
      pneumoniae as a model of local infection in the respiratory tract. Mycoplasma and
      ureaplasma infections of man are frequent, but rarely life threatening. Chick
      embryos, rats, hamsters, guinea pigs, and monkeys (rhesus monkeys and
      chimpanzees) are susceptible to experimental infection with M. pneumoniae. Some
      mouse strains are also colonized with M. pneumoniae after intranasal inoculation,
      but histopathological alterations similar to the hamster model have not been
      established in a reproducible way in mice. Hamsters have, therefore, been
      important for the evaluation of antibiotics and vaccines. Local immunity in the
      respiratory tract, the possible contribution of the immune response to disease
      pathogenesis, persistence of the organisms in the respiratory tract after
      clinical symptoms are cured by antibiotic therapy, and the role of cytokines in
      protection or disease pathogenesis remain interesting areas for future research,
      which could be addressed in animal models. The evaluation of the role of
      mycoplasmas and ureaplasmas in genital tract infections is by far more complex
      and even more difficult in AIDS and rheumatoid arthritis, because several species
      of mycoplasmas and Ureaplasma urealyticum can be isolated from a large proportion
      of healthy individuals. Furthermore, good models for the study of these
      infections are not available.

PMID- 9286062
TI  - Mycoplasma infections of the human respiratory tract.
AB  - Mycoplasma pneumoniae represents one of the common etiological agents causing
      interstitial pneumonia, but more often a long-lasting tracheobronchitis in
      children and also in adults. The incidence of Mycoplasma pneumoniae diseases
      varies considerably, major outbreaks being reported every 3 to 5 years. The
      pathomechanism of this agent is based on a unique, gliding motility, adhesion to
      respiratory epithelium cells and the induction of a pathological hyperstimulation
      of cellular response mechanisms of the host. Antigenic similarities between
      important functional sites of the adhesin of Mycoplasma pneumoniae and various
      host molecules might be one of the factors responsible for hindering the host
      response mechanism and, moreover, failing to protect the host repeated
      colonization. These are indications of a near perfect adaptation of Mycoplasma
      pneumoniae to man, its only known host to date.

PMID- 9286064
TI  - Mycoplasma hominis and Ureaplasma urealyticum in patients with sexually
      transmitted diseases.
AB  - Mycoplasma hominis and Ureaplasma urealyticum can be isolated with considerable
      frequency from the human urogenital tract and are thought to cause various
      syndromes such as nongonococcal urethritis, pelvic inflammatory disease,
      pyelonephritis or infertility. The aim of this study was the evaluation of the
      presence of different genital pathogens in patients with sexually transmitted
      diseases (STD) and, in particular, the detection of mycoplasmas in individuals
      infected with genital microbes and an assessment of the presence of genital
      microorganisms in patients harbouring Mycoplasma hominis or Ureaplasma
      urealyticum. Furthermore, the occurrence of mycoplasmas in women with bacterial
      vaginosis was established. Specimens were collected from a total of 41,980
      persons attending the Outpatients' Centre for Infectious Venero-Dermatological
      Diseases in Vienna from 1994 to 1996. Of all genital pathogens, Ureaplasma
      urealyticum was cultured most frequently in men and women. Mycoplasma hominis and
      Ureaplasma urealyticum were detected more often in the vaginal fluid than in the
      male urethra. By contrast, infection rates with Neisseria gonorrhoeae and
      Chlamydia trachomatis were higher in men than in women. In both men and women,
      trichomoniasis increased colonisation with Mycoplasma hominis, while mycoplasmas
      occurred less frequently together with genital candidiasis. Mycoplasma hominis
      was cultivated significantly more often in women with bacterial vaginosis than in
      those without. In contrast to urethral infections in men, cervical infections
      with Neisseria gonorrhoeae or Chlamydia trachomatis raised the incidence of
      Mycoplasma hominis in the vaginal fluid.

PMID- 9286063
TI  - Genital mycoplasma infections.
AB  - Since 1937, 13 Mycoplasma species, two Acholeplasma species, and one Ureaplasma
      species have been isolated from humans. Six of these have the urogenital tract as
      the primary site of colonisation but others, which have the oropharynx and
      respiratory tract as the primary site, are found occasionally in the urogenital
      tract because of orogenital contact. Mycoplasma hominis was the first to be
      isolated and is most strongly associated with bacterial vaginosis (BV), together
      with a variety of other bacteria. Its involvement in pelvic inflammatory disease
      (PID) and other conditions may be as part of BV, although when isolated in pure
      culture from the blood of women who have postpartum or postabortal fever there is
      no reason to suspect its aetiological role. There is evidence for an aetiological
      role for Ureaplasma urealyticum organisms (ureaplasmas) in acute non-gonococcal
      urethritis (NGU) and particularly chronic NGU in men, but they rank third to
      Chlamydia trachomatis and M. genitalium. Whether the association of ureaplasmas
      with miscarriage and preterm labour is in the context of BV is not clear. Of no
      doubt, however, is the ability of ureaplasmas to cause septic arthritis in
      hypogammaglobulinaemic patients and there is evidence that they may cause some
      cases of sexually acquired reactive arthritis. The advent of polymerase chain
      reaction technology has seen an advance in the understanding of the role of M.
      genitalium; there is strong evidence that it is one of the causes of both acute
      and chronic NGU independent of C. trachomatis. There is some support for the role
      of M. genitalium in PID, but this needs to be substantiated. Other mycoplasmas,
      for example M. fermentans, M. pivum, M. primatum, M. penetrans, M. spermatophilum
      and even M. pneumoniae have the capacity to cause urogenital tract disease but
      there is no evidence to indicate that they do so.

PMID- 9286065
TI  - Mycoplasmas and HIV infection, a possible interaction through immune activation.
AB  - The persistence of HIV in the host is associated with a state of chronic immune
      activation with deleterious effects. In addition to HIV, several infectious
      agents can contribute to this activation and, consequently, to an increased HIV
      load. We have postulated that mycoplasmas could act as cofactors of HIV,
      contributing to a faster progression of the disease through increased immune
      activation. Mycoplasma penetrans was shown to be associated with HIV infection
      and recent data have indicated the capacity of this mycoplasma to activate
      different functions of the immune system. However, its role as an HIV cofactor
      remains to be demonstrated.

PMID- 9286066
TI  - New developments in diagnostic and treatment of mycoplasma infections in humans.
AB  - Several methods can be used for the diagnosis of mycoplasmal human infections.
      Culture is not satisfactory for fastidious species, while serological procedures
      allow only a retrospective diagnosis. Recently, rapid methods have become
      available. Antigenic detection proposed for Mycoplasma pneumoniae lacks
      sensitivity. Hybridization based techniques include DNA probes and mainly DNA
      amplification. The main usefulness of the polymerase chain reaction (PCR) is the
      detection of fastidious organisms such as M. pneumoniae, M. genitalium, M.
      fermentans, M. penetrans, but PCR can also be used for characterization of the
      strains for epidemiological purposes, or for detection of antimicrobial
      resistance genes. The major advantage of PCR for detection is its very high
      sensitivity. However, until now, the major drawback of this technique has been
      the lack of commercial kits. When available, they should provide better
      standardization of the technique and, if available at a reasonable cost, become
      the major technique for the diagnosis of mycoplasma infections. The antibiotics
      used for the treatment of mycoplasmal infections belong to tetracyclines,
      macrolides-lincosamides and fluoroquinolones. These products are highly active in
      vitro against mycoplasmas. However, some of them have a differential activity
      according to the species, and acquired resistance has been reported, mainly in
      genital mycoplasmas. Most of mycoplasmal infections are cured by adapted
      antibiotics, but they may be difficult to cure in immunosuppressed patients.

PMID- 9286067
TI  - Molecular identification and epidemiology of animal mycoplasmas.
AB  - Molecular genetic techniques show a high potential for rapid and accurate
      identification of Mycoplasma species isolated from animals. An important field of
      application for such methods is the differentiation of species and/or subspecies
      which are phenotypically closely related, but which show significant differences
      in epidemiological impact. This need is particularly important for the
      mycoplasmas of the "mycoides group", which are phenotypically and
      phylogenetically very closely related. Molecular typing techniques based on 16S
      rRNA genes give straightforward phylogenetic answers on the species level. For
      more refined methods of subtyping at the subspecies level, the use of defined
      genes characteristic of certain Mycoplasma species or clusters is recommended.
      Genetic fingerprinting, especially insertion sequence typing has proved to be a
      valuable tool for subtyping and strain identification in particular of vaccine
      strains and for epidemiological investigations.

PMID- 9286068
TI  - Spiroplasmas: infectious agents of plants, arthropods and vertebrates.
AB  - The spiroplasmas are mollicutes characterized by motility and helical morphology.
      They were discovered through studies on corn stunt and citrus stubborn diseases.
      The stubborn agent was the first mollicute of plant origin to be obtained in
      culture and the first cultured mollicute to possess a helical morphology. The
      citrus pathogen has been known as Spiroplasma citri since 1973. The corn stunt
      agent was cultured in 1975 and fully characterized as Spiroplasma kunkelii by
      1986. The third and only other phytopathogenic spiroplasma is Spiroplasma
      phoeniceum, cultured from naturally infected periwinkle plants in Syria and
      described in 1986. These three spiroplasmas are restricted to the phloem
      sievetubes of the infected plants and are transmitted from plant by various
      phloem feeding leafhopper vectors in which the spiroplasmas multiply. Following
      the pioneering work on S. citri and S. kunkelii, close to fifty other spiroplasma
      species or proposed species have been discovered. All spiroplasmas have been
      isolated from insects, ticks and plants. Insects are particularly rich sources of
      spiroplasmas. Some insect-derived spiroplasmas are entomopathogens. S. melliferum
      and S. apis are honey bee pathogens. They cross the insect-gut barrier and reach
      the hemolymph, where they multiply abundantly and kill the bee. Spiroplasma
      floricola is the agent of lethargy disease of Melolontha melolontha (cockchafer).
      Spiroplasma poulsonii infects the neotropical species of Drosophila, is
      transmitted transovarially and kills the male progeny of an infected female fly,
      hence the name sex ratio spiroplasma. Some insect-derived spiroplasmas are also
      found on plant (flower) surfaces. For instance, S. apis was cultured from the
      surfaces of flowers growing in the vicinity of affected beehives. This suggests
      that the plant surface spiroplasmas are deposited on these surfaces by
      contaminated insects. Many insect spiroplasmas are not pathogenic, are often
      restricted to the gut and may be regarded as mutualists or incidental commensals.
      Of the three known tick spiroplasmas, only Spiroplasma mirum obtained from rabbit
      ticks is pathogenic to the vertebrate animal (chick embryo, new-born rodents,
      adult rabbit), but only upon experimental inoculation of the spiroplasma. Strain
      SMCA induces high incidence of cataracts in new born rodents. With strain GT-48
      no cataracts are observed, but fatal encephalitis occurs. Spiral membranous
      inclusions resembling spiroplasmas have been seen in brain biopsies taken from
      patients with Creutzfeldt-Jakob disease. However, failure to detect spiroplasmas
      by serology and culture points to the absence of spiroplasmal involvement in
      spongiform encephalopathies. Transposon Tn 4001 mutagenesis has been applied for
      the first time to Spiroplasma citri, and pathogenicity can now be studied at the
      genetic level. One Tn 4001 mutant does not multiply in the leafhoppers and is,
      therefore, not transmitted to the plant. Another mutant multiplies well in the
      plant and is transmitted to the plant, where it reaches high titers, but without
      inducing symptoms in the plant. In this non-phytopathogenic mutant, Tn 4001 is
      inserted in the spiroplasmal fructose operon, and the mutant is unable to use
      fructose. Finally, to study involvement of spiroplasmal motility in
      pathogenicity, a non-motile mutant has been obtained. Motility was restored by
      complementation with the wild type genes. This is the first time that successful
      complementation has been reported, not only in the spiroplasmas but in the
      mollicutes in general. Undoubtedly, studies on pathogenicity have entered a new
      era.

PMID- 9286069
TI  - Non-cultivable phytopathogenic mycoplasmas: characterization, detection and
      perspectives for control.
AB  - Phytoplasmas (ex MLOs) and spiroplasmas are important groups of plant pathogenic
      mollicutes, discovered in 1967 and 1970 respectively. Spiroplasmas, like other
      mollicutes, can be cultured in artificial media and are thus well characterized.
      On the contrary, phytoplasmas have resisted in vitro cultivation and their study
      was difficult until the recent development of molecular techniques. From the
      sequence of their 16S rDNA, phytoplasmas have been shown to be true mollicutes.
      Fourteen phytoplasma subclasses have been defined, but only two phytoplasmas have
      so far been named at the genus and species level. Monoclonal antibodies, DNA
      probes and PCR primers for the specific detection of various phytoplasmas have
      been obtained. These showed that a given phytoplasma can infect a broad range of
      plants, while others are restricted to a single plant species. Specific reagents
      are also used for identification of insect vectors and reservoir plants of the
      various phytoplasmas. Plant pathogenic mollicutes cannot be controlled chemically
      today, since the use of antibiotic treatment is forbidden in agriculture.
      However, the growth and metabolism of mollicutes are known to be inhibited by
      antibodies and this provides a hopeful approach for future control of these
      agents in plants. Indeed, it has been shown recently that plants can be
      engineered to express and assemble functional immunoglobulin chains. Transgenic
      tobacco plants expressing an antibody against the stolbur phytoplasmas have been
      developed. They have now to be challenged with the phytoplasma to determine if
      they have acquired resistance to this mollicute.

PMID- 9286070
TI  - Cardiac rehabilitation and risk factor management after myocardial infarction.
      Clinical and economic evaluation.
AB  - The increasing scarcity of available, and finite, health care resources, and the
      increased demands for health care, have made consideration of effectiveness and
      cost-effectiveness of health care services, such as the secondary prevention of
      heart disease, an imperative. There is considerable evidence that modification of
      cigarette smoking, hyperlipidemia, hypertension, and lack of physical activity,
      either singly or in combination, are effective in reducing the number of clinical
      events in the secondary prevention of heart disease. Economic evaluation is the
      comparative analysis of alternative courses of action in terms of both costs and
      consequences. Data generated in economic evaluations of health care services,
      such as risk factor modification in the secondary prevention of heart disease,
      are useful in developing clinical practice guidelines and health policies.
      Smoking cessation is the most cost-effective intervention for patients with
      documented heart disease while treatment of hyperlipidemia and referral to
      cardiac rehabilitation are highly cost-effective per quality-adjusted life year
      and relatively cost-effective per year of life saved. Risk factor management,
      provided by a team including cardiovascular specialists and other physicians
      together with appropriately trained allied health professionals, is the
      cornerstone of optimal care in both the primary and secondary prevention of heart
      disease.

PMID- 9286071
TI  - [Value of antioxidants and vitamins in cardiovascular prevention and therapy].
AB  - Experimental as well as epidemiological data suggest the use of antioxidants for
      therapy of atherosclerosis. Feasible, however, seems only the use of antioxidant
      vitamins. Recent knowledge from published data seems to justify the use of low
      dose supplementation in primary prevention of vascular disease. High-dose
      intervention in secondary prevention, despite promising results from intervention
      studies, needs further controlled studies, addressing optimal dose or combination
      therapies.

PMID- 9286072
TI  - Ultrasound in the investigation of tubal patency. A meta-analysis of three
      comparative studies of Echovist-200 including 1007 women.
AB  - DESIGN: This study is a meta-analysis of the results of three clinical studies of
      the ultrasound echo-contrast agent Echovist-200 with transvaginal contrast
      sonography (HyCoSy) in the demonstration of tubal patency. Results from 1007
      patients were included in the analysis, of whom 986 patients were examined for
      tubal patency. The HyCoSy findings were compared with those of chromolaparoscopy
      in 428 cases and with those of hysterosalpingography (HSG) in 202. RESULTS: The
      results of HyCoSy and chromolaparoscopy were identical in 294 of 428 patients
      (68.7%) or in 688 of 828 individual tubes (83.1%). HyCoSy showed "false"
      occlusion in 85 tubes (10.3%) and "false" patency in 55 (6.7%). The results of
      HyCoSy and HSG were identical in 138 of 202 patients (68.3%) or in 320 of 384
      individual tubes (83.3%). HyCoSy showed "false" occlusion in 49 tubes (12.8%) and
      "false" patency in 15 (3.9%). The findings of chromolaparoscopy and HSG agreed in
      49 of 77 patients (63.6%) or in 116 of 152 tubes (76.3%). HSG showed "false"
      occlusion in 19 (12.5%) tubes and "false" patency in 17 (11.2%). TOLERANCE:
      Echovist-200 was well tolerated. The most frequent adverse event was pain, which
      was mild in 42.3% of patients and severe in 10.1%. Pain was clearly related to
      tubal occlusion. Other adverse events such as vasovagal reactions or nausea
      occurred in 7.0% of patients, but the events required treatment in only 1.9%.

PMID- 9286073
TI  - Model discrimination and estimation of the intraparticle mass transfer parameters
      for the adsorption of bovine serum albumin onto porous adsorbent particles by the
      use of experimental frontal analysis data.
AB  - Experimental data from a chromatographic system involving the adsorption of
      bovine serum albumin (BSA) onto porous anion-exchange adsorbent particles packed
      in a column are presented. The parameters that characterize the mass transfer
      mechanisms of intraparticle diffusion and convection are estimated by fitting the
      predictions of dynamic mathematical models describing adsorption in column
      systems having spherical perfusive and purely diffusive adsorbent particles to
      the experimental breakthrough data obtained from the column adsorption system.
      Both linear and nonlinear expressions for the equilibrium isotherm are
      considered. The values of the transport parameters are estimated in the time
      domain for the nonlinear adsorption models and in the Laplace transform domain
      for the linear adsorption models. The capabilities of the different models to
      describe satisfactorily the dynamic behavior of the adsorption system are
      compared. The dynamic nonlinear adsorption model for purely diffusive particles
      is found to describe most appropriately the dynamic behavior of the experimental
      chromatographic system studied in this work.

PMID- 9286074
TI  - Kinetic analysis of the interaction between the monoclonal antibody A33 and its
      colonic epithelial antigen by the use of an optical biosensor. A comparison of
      immobilisation strategies.
AB  - The interaction between the humanised A33 monoclonal antibody and the
      corresponding F(ab)'2 or Fab' fragments with the colonic epithelial A33 antigen,
      purified by micropreparative HPLC from membrane extracts of the colonic carcinoma
      cell line LIM 1215, has been studied with the BIAcore 2000 biosensor using
      surface plasmon resonance detection. The surface orientation of immobilised
      antibody and the Fab' fragment onto the biosensor surface was controlled using
      alternative immobilisation chemistries. This resulted in significantly higher
      molar binding activities compared with the conventional N-hydroxysuccinimide
      (NHS)/N-ethyl-N'-dimethylaminopropylcarbodiimide (EDC) chemistry. This increase
      in signal resulted in a concomitant increase in sensitivity of detection, which
      facilitates analysis of low levels of A33 antigen. The apparent association rate
      (ka) and dissociation rate (kd) constants obtained with the different
      immobilisation chemistries were determined. These analyses showed that the
      kinetic constants obtained for the IgG were not significantly affected by the
      method of immobilisation. F(ab)'2 and Fab' fragments immobilised using NHS/EDC
      chemistry showed significantly lower apparent affinity. By contrast the use of
      the thiol coupling chemistry with the Fab' fragment gave a five fold increase in
      observed KA, resulting in a similar affinity to that observed with the intact IgG
      molecule.

PMID- 9286075
TI  - Study of the binding of antibiotics to human serum albumin by charge-transfer
      chromatography.
AB  - The interaction of 13 antibiotics with human serum albumin was studied by charge
      transfer reversed-phase thin-layer chromatography in neutral, acidic, basic and
      ionic environments (NaCl and MgCl2) and the relative strength of interaction was
      calculated. The pH and the presence of mono- and divalent cations markedly
      influenced the strength of interaction. The capacity of antibiotics to interact
      with HSA also considerably depended on their chemical structure.

PMID- 9286076
TI  - Enantiomeric properties of human albumin immobilized on porous silica supports
      coated with polymethacryloyl chloride.
AB  - Human serum albumin (HSA) was bound to porous silica, using a reactive polymer
      derived from polymethacryloyl chloride. Two different procedures were used for
      coating silica with the polymer. In the first method, the polymer was deposited
      onto amino-silica by reaction between its reactive functions and NH2 groups on
      silica. In the second method, the monomer was first linked to the amino-silica
      and copolymerization with the excess of monomer initiated thereafter. The
      enantiomeric properties of the resulting supports after the coupling of HSA were
      compared using different mobile phases. The higher amount of HSA bound using the
      later method, resulted in higher retention of the enantiomers and better
      enantioselectivity.

PMID- 9286077
TI  - Enantioselectivity properties of human serum albumin immobilized on anion
      exchangers based on polyvinylimidazole-coated silica. Effect of protein loading
      on separation properties.
AB  - Chiral chromatographic supports were obtained by continuously applying solutions
      contained HSA to ion-exchange columns. The columns were packed with silica
      modified with polyvinylimidazole and a copolymer polyvinylpyrrolidone
      polyvinylimidazole (75:25) respectively, quaternized and crosslinked. Small
      changes in the concentration of NaCl during immobilization of HSA lead to
      variations in the amount of HSA bound to the supports. These variations have
      consequences in terms of chromatographic retention (k'), selectivity (alpha) and
      resolution (Rs) of enantiomers. The effects of varying the pH and organic
      modifier of the mobile phase on the chromatographic properties were also
      examined.

PMID- 9286078
TI  - Modification of polystyrenic matrices for the purification of proteins. II.
      Effect of the degree of glutaraldehyde-poly(vinyl alcohol) crosslinking on
      various dye ligand chromatography systems.
AB  - A poly(styrene-divinylbenzene) chromatography matrix, CG1000sd (TosoHaas) has
      been modified by the adsorption and crosslinking of poly(vinyl alcohol) (PVA) to
      create a matrix suitable for the attachment of dye ligands for the adsorption of
      lysozyme. However, it is shown that there was limited recovery and repeated drops
      in capacity with adsorption of human serum albumin (HSA). The effect of changing
      the nature of the PVA crosslinking on the HSA binding characteristics was
      studied, as well as the effect of using differing dye ligands. The total amount
      of irreversible HSA binding decreased with greater crosslinking and there were
      large differences in HSA adsorption characteristics between differing dye types.

PMID- 9286079
TI  - Modification of polystyrenic matrices for the purification of proteins. III.
      Effects of poly(vinyl alcohol) modification on the characteristics of protein
      adsorption on conventional and perfusion polystyrenic matrices.
AB  - Poly(styrene-divinylbenzene) (PS-DVB) chromatography matrices, CG1000sd 20-50
      microns (TosoHaas), PLRP4000s 15-25 microns, PLRP4000s 50-70 microns (Polymer
      Laboratories) have been modified by the adsorption and crosslinking of poly(vinyl
      alcohol) (PVA) to create a matrix suitable for the attachment of dye ligands. The
      adsorption capacities of lysozyme and HSA on these Procion Yellow HE-3G dyed PVA
      modified PS-DVB matrices were measured at various flow-rates and the capacities
      were compared with a Procion Yellow HE-3G dyed OH-activated POROS 20, 20-micron
      matrix (PerSeptive Biosystems). The adsorption of small proteins was not hindered
      by the smaller pores of the CG1000sd beads, but as protein size increased, and at
      high flow-rates, a high mass transfer rate became more dependent on large pore
      size and small particle diameter.

PMID- 9286080
TI  - D-Glucose, forskolin and cytochalasin B affinities for the glucose transporter
      Glut1. Study of pH and reconstitution effects by biomembrane affinity
      chromatography.
AB  - The affinities of D-glucose and the transport inhibitors, forskolin and
      cytochalasin B (CB), for Glut1 were studied by frontal affinity chromatography at
      pH 5-10 on sterically immobilized proteoliposomes with reconstituted human red
      cell glucose transporter Glut1. The affinity of D-glucose for Glut1 became
      slightly weaker as the pH was increased. The inhibitor affinities decreased and
      became immeasurably weak above pH 9. At pH 7.4, the dissociation constants were
      44 mM for glucose, 1.8 microM for forskolin and 72 nM for CB. The affinities of
      these solutes for Glut1 in red cell membrane vesicles and particularly for Glut1
      in red cells were higher, as shown by chromatographic analyses.

PMID- 9286081
TI  - Glucose affinity for the glucose transporter Glut1 in native or reconstituted
      lipid bilayers. Temperature-dependence study by biomembrane affinity
      chromatography.
AB  - The affinity of D-glucose and the transport inhibitor cytochalasin B (CB) for the
      glucose transporter Glut1 was studied at 5-42 degrees C by quantitative frontal
      affinity chromatography on sterically immobilized human red cell membrane
      vesicles, and on proteoliposomes containing reconstituted red cell membrane
      proteins. Glut1 in the vesicles showed the highest glucose affinity; the
      dissociation constant Kd(glc) was nearly constant (16 +/- 3 mM) from 15 degrees C
      to 37 degrees C. For Glut1 in proteoliposomes Kd(glc) decreased from 56 mM at 5
      degrees C to 26 mM at 42 degrees C. The CB-Glut1 affinity was strongest around 20
      degrees C and was mostly higher with the vesicles, Kd (CB) being 49 nM at 19
      degrees C. The entropy and entropy and enthalpy changes for the interactions were
      calculated.

PMID- 9286082
TI  - Chromatographic method involving inductively coupled plasma atomic emission
      spectrometric detection for the study of metal-protein complexes.
AB  - A chromatographic method has been used to study metal ion-protein complexes. It
      involves successively a gel filtration technique to separate and distinguish the
      complexed from the free metallic ions, and a spectrometric technique, inductively
      coupled plasma atomic emission spectrometry (ICP-AES), which allows us to
      calculate accurately the concentration of ionic metallic species in solution. In
      the chromatographic step, we applied a large-zone Hummel and Dreyer method. Thus,
      fractions can be collected throughout the chromatographic experiment and their
      metal concentration measured by ICP-AES, at constant and known protein
      concentration. This method has been tested on the copper complex of bovine serum
      albumin. Results of our study are in good agreement with previous studies on this
      complex.

PMID- 9286083
TI  - Size-exclusion chromatographic reconstitution of the bovine brain benzodiazepine
      receptor. Effects of lipid environment on the binding characteristics.
AB  - The benzodiazepine receptor from calf brain was solubilized with sodium
      deoxycholate (2 mg/ml) in the presence of 0.5 M KCl and protease inhibitors, and
      bound flunitrazepam with an equilibrium dissociation constant (Kd) of 2.7 +/- 1.2
      nM and with 0.40 +/- 0.04 pmol binding sites per mg protein (Bmax). Up to 60% of
      the benzodiazepine binding sites (average 25%) could be reconstituted in lipid
      vesicles, upon size-exclusion chromatography of protein-detergent-lipid mixtures
      on Sephadex G-50 Medium for detergent depletion. The flunitrazepam affinity for
      the reconstituted receptor varied with the lipid composition (Kd 1.4-4 nM).
      Freezing and thawing increased the size of the small proteoliposomes obtained by
      chromatographic reconstitution and, on the average, doubled the number of
      operative flunitrazepam binding sites. When the proteoliposomes were stored at 
      20 degrees C or -80 degrees C or in lyophilized state, the receptor retained its
      benzodiazepine binding affinity and Bmax over a period of 2 months.

PMID- 9286084
TI  - Two-dimensional electrophoretic analysis of vesicular and micellar proteins of
      gallbladder bile.
AB  - Proteins associated with lipid vesicles or mixed micelles of human gallbladder
      bile were separated by Sepharose-2B gel filtration chromatography followed by
      protein concentration and delipidation. After two-dimensional polyacrylamide gel
      electrophoresis and silver staining up to 59 and 471 polypeptide spots were
      counted in vesicular and micellar fractions, respectively. As major components
      the plasma proteins transferrin, albumin, alpha-fibrinogen, beta-fibrinogen,
      gamma-immunoglobulin G, immunoglobulin light chains, alpha-1 antitrypsin and
      haptoglobin alpha-2 chain were identified in the lipid vesicles by comparison
      with human protein reference maps. However, most biliary proteins including the
      anionic polypeptide fraction are associated with mixed micelles. The
      pathophysiological significance of these proteins associated with lipids needs to
      be investigated further.

PMID- 9286085
TI  - Mapping of peptides and protein fragments in human urine using liquid
      chromatography-mass spectrometry.
AB  - A method for the mapping of peptide mixtures, heterogeneous with respect to the
      concentration and the size of individual peptides, was established with the aim
      of obtaining a comprehensive analysis of human urine peptides. Peptide extraction
      and fractionation were optimized to achieve a two-step analysis, using reversed
      phase and ion-exchange chromatography. Highly sensitive detection of peptides was
      performed by coupling microbore HPLC with electrospray mass spectrometry (ESI
      MS). Peptides such as urodilatin, angiotensin and fragments of psoriasin,
      granulin and uromodulin were isolated and sequenced. The procedure presented here
      is a tool for the analysis of complex peptide mixtures from human urine.

PMID- 9286086
TI  - Peptide bank generated by large-scale preparation of circulating human peptides.
AB  - Human hemofiltrate (HF) is a source for the purification of circulating
      regulatory peptides. HF is obtained in large quantities during treatment of
      patients suffering from chronic renal failure. We have developed a large-scale
      method for separating peptides from amounts up to 10,000 1 HF into 300 fractions
      in a standardized two-step procedure, employing cation-exchange separation,
      followed by reversed-phase chromatography. These fractions represent a peptide
      bank containing bioactive, desalted and lyophilized peptides of blood. Screening
      for and isolation of regulatory human peptides is simplified by using this
      peptide bank.

PMID- 9286087
TI  - Capillary electrophoresis in the assay of the hydrolysis of glycine-containing
      peptides by a protease from Pseudomonas aeruginosa.
AB  - A rapid and simple capillary zone electrophoresis (CZE) method for measuring the
      activity of a minor protease from Pseudomonas aeruginosa is described. When
      glycine-containing oligopeptides were used as substrates, it was possible to
      separate and quantify substrate and products. Moreover oligopeptide hydrolysates
      were analysed by fast atom bombardment mass spectrometry providing the sites of
      splitting of the substrates. By comparison with CZE calibration curves
      constructed with reference peptides, the initial rates of hydrolysis were
      calculated. The method, validated for pentaglycine hydrolysis, was also used for
      the analysis of reaction mixtures and for monitoring the enzymic hydrolysis of
      various peptides in order to investigate enzyme specificity.

PMID- 9286088
TI  - Matrix-assisted laser desorption/ionisation mass spectrometry guided purification
      of human guanylin from blood ultrafiltrate.
AB  - The purification of the human peptide hormone guanylin 22-115 from blood
      ultrafiltrate (hemofiltrate, HF) was achieved using matrix-assisted laser
      desorption/ionisation mass spectrometry (MALDI-MS) as the assay system. Screening
      a peptide bank generated from 5000 1 HF guanylin 22-115 was detected by its
      molecular mass when adequate conditions for MALDI-MS analysis were chosen. The
      sensitivity was even better than of the established biological assay system. In
      addition, the susceptibility towards solvents and salts is strongly reduced. 1.2
      mg of the peptide hormone was purified from 10% of the starting material.

PMID- 9286089
TI  - Use of sodium perchlorate at low pH for peptide separations by reversed-phase
      liquid chromatography. Influence of perchlorate ion on apparent hydrophilicity of
      positively charged amino acid side-chains.
AB  - The reversed-phase liquid chromatography (RPLC) behavior of synthetic model
      peptides containing positively charged amino acid residues was studied in the
      presence or absence of 100 mM sodium perchlorate in order to determine the effect
      on apparent side-chain hydrophilicity of a charged residue at low pH. The
      peptides used in this study were either non-helical peptides or amphipathic alpha
      helical peptides, where the effect of the negatively charged perchlorate ion on a
      charged residue in either the hydrophobic face or hydrophilic face of the helix
      was monitored. We have shown that the addition of 100 mM perchlorate to RPLC
      separations of positively charged peptides performed in a 20 mM aqueous
      phosphoric acid-acetonitrile system resulted in an increase in retention time of
      a peptide relative to the same peptide in the absence of perchlorate. This effect
      occurred independent of conformation, i.e., whether comparing the effect of
      positively charged residue substitutions in the hydrophobic or hydrophilic face
      of an amphipathic alpha-helix or in a peptide with negligible secondary
      structure. From these results, suggesting that positively charged side-chain
      hydrophilicity is decreased by ion-pairing with the perchlorate ion, we have
      shown practical examples where mixtures of non-helical and amphipathic alpha
      helical peptides showed enhanced resolution in the presence of perchlorate at pH
      2, compared to in its absence. In addition, it was shown that an aqueous
      phosphoric acid-perchlorate-acetonitrile mobile phase may show markedly different
      selectivity for peptide separations at low pH compared to the more traditional
      aqueous trifluoroacetic acid-acetonitrile system.

PMID- 9286090
TI  - Dietary cholesterol enhances torpor in a rodent hibernator.
AB  - Dietary cholesterol can affect both body lipid composition and steroid hormone
      concentration. We investigated whether a diet rich in cholesterol influences
      torpor patterns of hibernating chipmunks (Tamias amoenus) and, if so, whether
      these changes are better explained by diet-induced changes in body lipid
      composition or the concentration of testosterone, which at high levels inhibits
      torpor. Two groups of chipmunks were maintained either on a cholesterol diet
      (rodent chow containing 10% cholesterol) or a control diet (rodent chow) during
      pre-hibernation fattening and throughout the hibernation season. Torpid chipmunks
      on the cholesterol diet had significantly lower minimum body temperatures (-0.2
      +/- 0.2 vs -0.6 +/- 0.2 degree C), lower metabolic rates (0.029 +/- 0.002 ml O2 g
      1 h-1 vs 0.035 +/- 0.001 ml O2 g-1 h-1), and longer torpor bouts at -1 degree C
      (6.8 +/- 0.5 vs 4.1 +/- 1.0 days) than chipmunks on the control diet. Dietary
      cholesterol resulted in a significant increase in blood plasma cholesterol
      (sevenfold), liver cholesterol content (6.9-fold) and liver triglyceride content
      (3.5-fold) in comparison to controls. In contrast, dietary cholesterol had no
      detectable effect on the concentration of plasma testosterone, which was very low
      in both groups. Since torpor was deeper and longer in animals on the cholesterol
      diet our study suggests that torpor patterns of chipmunks were either directly
      affected by the dietary cholesterol or via changes in body lipid composition.

PMID- 9286091
TI  - Hormonal and metabolic adaptations to fasting in monosodium glutamate-obese rats.
AB  - The effect of fasting on hormonal and metabolic variables was evaluated in normal
      rats and in rats with obesity induced by neonatal treatment with monosodium
      glutamate (MSG). The hyperinsulinemia of the fed obese rats was reversed by
      fasting. Plasma corticosterone was also high in the fed obese and decreased to
      levels similar to fed controls, while it increased in the latter group during
      fasting. In contrast, thyroid hormone levels decreased in controls but increased
      in the obese rats in response to fasting. The fed obese group had lower carcass
      protein and higher carcass lipid contents than controls. In response to fasting,
      the decrements of the initial amount of both protein and fat were lower in MSG
      than in controls. Fasting induced a sustained increase in plasma free fatty acids
      only in the obese rats, although a single 100 mumol.l-1 dose of norepinephrine
      stimulated in vitro glycerol release more pronouncedly in epididymal adipocytes
      from control than obese rats. The results indicate that MSG-obese rats were able
      to mobilize fat stores during prolonged fasting. The high availability of lipid
      fuels and the sharp and sustained decrease in circulating corticosterone in the
      MSG group were probably important in diminishing body protein consumption during
      fasting.

PMID- 9286092
TI  - Effect of manipulation of the renin-angiotensin system in control of drinking in
      juvenile Atlantic salmon (Salmo salar L) in fresh water and after transfer to sea
      water.
AB  - Drinking in Atlantic salmon (Salmo salar) juveniles was investigated in fresh
      water and following transfer to sea water. There was a significant effect of fish
      size on drinking, and smolts (20-30 g) imbibed about ten times less water than
      alevins of 0.2-0.3 g. Freshwater smolts drank at a rate of 0.15 +/- 0.03 ml.kg
      1.h-1 and administration of doses of 10 or 20 mg.kg-1 of papaverine (stimulator
      of the renin-angiotensin system RAS) or [Asn1, Val5]-Angiotensin II (0.4 mumol.kg
      1) resulted in significant increases in drinking, while administration of the
      angiotensin converting enzyme inhibitor, enalapril (50 mg.kg-1) had no effect on
      drinking. Transfer of Atlantic salmon smolts to 1/3, 2/3 and full strength sea
      water resulted in significant increases in drinking to 1.06 +/- 0.12, 1.24 +/-
      0.0.16 and 3.89 +/- 0.28 ml.kg-1.h-1, respectively. In sea water, stimulation of
      the endogenous RAS by administration of papaverine (20 mg.kg-1) resulted in a 20%
      increase in drinking, while administration of enalapril to doses of 50 and 200
      mg.kg-1 lowered drinking to 1.99 +/- 0.48 and 0.32 +/- 0.06 ml.kg-1.h-1,
      respectively. All treatments were without effect on blood plasma levels of Na+
      and Cl- in fresh water, while in sea water smolts both stimulation and inhibition
      of drinking resulted in hemoconcentration of Na+ and Cl-. The role of the renin
      angiotensin system in control of drinking and hydromineral balance in Atlantic
      salmon is discussed.

PMID- 9286093
TI  - Vocal development in budgerigars (Melopsittacus undulatus): contact calls.
AB  - Budgerigars have a complex vocal repertoire, some of which develops through
      learning. The authors examined the course of vocal development in budgerigars
      from hatching to about 4 weeks postfledging (approximately 85 days old). Food
      begging calls showed changes in duration, peak frequency, bandwidth, and
      frequency modulation with age. Within a week of fledging, each bird produced a
      contact call bearing a strong resemblance to a shortened version of its patterned
      food-begging call. By 4 weeks postfledging, budgerigar contact call repertoires
      often contained more than one call type, and there was clear evidence of sharing
      and imitation among the calls of parents, fledglings, and other social
      companions. Perceptual testing showed that whereas acoustic variation in the
      structure of developing calls decreased both within and between nestling birds,
      the discrimination of these calls was easier for adult birds as young birds
      matured. These results suggest parallels with certain aspects of language
      development in humans.

PMID- 9286094
TI  - The role of nasal chemical senses in garter snake response to airborne odor cues
      from prey.
AB  - Garter snakes increase tongue-flick rates in the presence of airborne odorants
      (amyl acetate, limonene, earthworm wash vapor, fish water vapor, earthworms,
      goldfish) but not water vapor. Main olfactory (MO) nerve lesions result in loss
      of this tongue-flick rate elevation in the presence of airborne odorants.
      Vomeronasal (VN) nerve lesions result in a diminution of tongue-flick rate
      elevation. Garter snakes discriminate between the 2 arms of a maze containing
      airborne earthworm odor as compared with a blank control. Following MO nerve
      lesions, snakes fail to make this discrimination. Following VN nerve lesions or
      VN duct suture, snakes are initially able to make the discrimination but may
      eventually cease to prefer the prey-odor side of the maze and may stop eating
      prey rewards. These results support the idea that airborne odorants are detected
      by the main MO system and that such detection does not require a functional VN
      system.

PMID- 9286095
TI  - Perceptual salience of acoustic features of Japanese monkey coo calls.
AB  - Smooth early high (SEH) and smooth late high (SLH) coo calls differ in the
      temporal location of a frequency inflection and are generally used in different
      situations. Coo quality is also influenced by additional features, such as
      relative harmonic level, which may have communicative significance. The authors
      used multidimensional scaling to analyze the perceptual similarity of SEH and SLH
      coos. Neither the temporal position of the frequency inflection nor caller
      identity could explain the coo groupings. Only the temporal relationships of the
      relative harmonic levels consistently differed between stimulus clusters.
      Relative level manipulations were conducted on synthetic coo replicas, resulting
      in substantial stimulus space reorganization. Although temporal position of the
      frequency inflection may provide the basis for coo classification, the authors
      suggest that relative harmonic amplitude can also influence response properties.

PMID- 9286097
TI  - Sublingual plicae (anterior processes) are not necessary for garter snake
      vomeronasal function.
AB  - The anterior processes of snakes may transfer odorants from the tongue to the
      vomeronasal (VN) organ. To test whether the anterior processes are required for a
      vomeronasally mediated behavior, the authors tested garter snakes (Thamnophis
      sirtalis) preoperatively and after cauterization of the anterior processes or
      control cauterization with artificial earthworms covered with earthworm wash
      (EWW) or distilled water. Snakes in both groups attacked EWW-covered artificial
      worms but not controls both pre- and postoperatively. In addition, snakes with
      anterior processes cauterization or control cauterization tongue flicked 3H
      proline. Radioautographs of the VN organs of snakes with and without anterior
      processes were indistinguishable: Snakes in both groups had reduced silver grains
      over the VN sensory epithelium as had been reported previously with intact
      snakes. These findings indicate that the anterior processes are unnecessary both
      for a behavior known to require a functional VN system and for delivery of
      odorants to the VN organ.

PMID- 9286096
TI  - Gaze following and joint attention in rhesus monkeys (Macaca mulatta).
AB  - Gaze and attention direction provide important sources of social information for
      primates. Behavioral studies show that chimpanzees spontaneously follow human
      gaze direction. By contrast, non-ape species such as macaques fail to follow gaze
      cues. The authors investigated the reactions of rhesus macaques (Macaca mulatta)
      to attention cues of conspecifics. Two subjects were presented with videotaped
      images of a stimulus monkey with its attention directed to 1 of 2 identical
      objects. Analysis of eye movements revealed that both subjects inspected the
      target (object or position attended by the stimulus monkey) more often than the
      distractor (nonattended object or position). These results provide evidence that
      rhesus monkeys follow gaze and use the attention cues of other monkeys to orient
      their own attention to objects.

PMID- 9286098
TI  - In situ biomechanics of the syrinx and sound generation in pigeons.
AB  - The in situ biomechanics of the vocal organ, the syrinx, was studied in
      anesthetized pigeons using fiberoptic instruments. The role of syringeal muscles
      was determined by electrical stimulation, and phonation was induced by injecting
      gas into the subsyringeal air sacs. This study presents the first direct
      observations of the biomechanical processes that occur in an intact syrinx.
      Contraction of one of the syringeal muscles, the m. tracheolateralis (TL),
      withdraws the lateral tympaniform membranes (LTM) from the syringeal lumen,
      causing opening of the syringeal airways. Shortening of a second muscle, the
      sternotrachealis (ST), draws the syringeal cartilages closer to each other,
      causing the LTM to fold into the syringeal lumen. Maximal ST contraction does not
      lead to complete closure of the syrinx. As air-sac pressure is increased by the
      injection of gas, the LTM are drawn into the syringeal lumen and balloon in a
      rostral direction until they touch, thus forming a fold-like valve. Air-induced
      phonation is always associated with vibrations of the membrane folds, suggesting
      that pulsatile release of air into the trachea by vibratory motion of the LTM
      generates sound. During air-induced phonation, strong stimulation of the TL
      terminates sound generation by abducting the LTM, whereas weak stimulation
      changes the geometry of the membrane folds, which is accompanied by changes in
      the acoustic structure of the sound. Stimulation of the ST has little effect on
      air-induced sounds. The LTM appear to be the main sound generators, since
      disabling the medial tympaniform membranes (MTM) with tissue adhesive does not
      prevent phonation or change the frequency and amplitude structure of display coos
      in spontaneously vocalizing pigeons. Moreover, the activity of the syringeal
      muscles appears to have a mainly modulatory function, suggesting that the basic
      sound-generating mechanism is similar in both air-induced and natural phonation.

PMID- 9286099
TI  - Mechanics of locomotion in lizards.
AB  - Lizards bend their trunks laterally with each step of locomotion and, as a
      result, their locomotion appears to be fundamentally different from mammalian
      locomotion. The goal of the present study was to determine whether lizards use
      the same two basic gaits as other legged animals or whether they use a
      mechanically unique gait due to lateral trunk bending. Force platform and
      kinematic measurements revealed that two species of lizards, Coleonyx variegatus
      and Eumeces skiltonianus, used two basic gaits similar to mammalian walking and
      trotting gaits. In both gaits, the kinetic energy fluctuations due to lateral
      movements of the center of mass were less than 5% of the total external
      mechanical energy fluctuations. In the walking gait, both species vaulted over
      their stance limbs like inverted pendulums. The fluctuations in kinetic energy
      and gravitational potential energy of the center of mass were approximately 180
      degrees out of phase. The lizards conserved as much as 51% of the external
      mechanical energy required for locomotion by the inverted pendulum mechanism.
      Both species also used a bouncing gait, similar to mammalian trotting, in which
      the fluctuations in kinetic energy and gravitational potential energy of the
      center of mass were nearly exactly in phase. The mass-specific external
      mechanical work required to travel 1 m (1.5 J kg-1) was similar to that for other
      legged animals. Thus, in spite of marked lateral bending of the trunk, the
      mechanics of lizard locomotion is similar to the mechanics of locomotion in other
      legged animals.

PMID- 9286100
TI  - Maximum speed and mechanical power output in lizards.
AB  - The goal of the present study was to test the hypothesis that maximum running
      speed is limited by how much mechanical power the muscular system can produce. To
      test this hypothesis, two species of lizards, Coleonyx variegatus and Eumeces
      skiltonianus, sprinted on hills of different slopes. According to the hypothesis,
      maximum speed should decrease on steeper uphill slopes but mechanical power
      output at maximum speed should be independent of slope. For level sprinting, the
      external mechanical power output was determined from force platform data. For
      uphill sprinting, the mechanical power output was approximated as the power
      required to lift the center of mass vertically. When the slope increased from
      level to 40 degrees uphill, maximum speed decreased by 28% in C. variegatus and
      by 16% in E. skiltonianus. At maximum speed on a 40 degrees uphill slope in both
      species, the mechanical power required to lift the body vertically was
      approximately 3.9 times greater than the external mechanical power output at
      maximum speed on the level. Because total limb mass is small in both species (6
      16% of body mass) and stride frequency is similar at maximum speed on all slopes,
      the internal mechanical power output is likely to be small and similar in
      magnitude on all slopes. I conclude that the muscular system is capable of
      producing substantially more power during locomotion than it actually produces
      during level sprinting. Thus, the capacity of the muscular system to produce
      power does not limit maximum running speed.

PMID- 9286101
TI  - Chloride secretion drives urine formation in leech nephridia.
AB  - The transport mechanisms underlying urine formation in leech nephridia were
      investigated in situ and in isolated preparations using pharmacological,
      electrophysiological and micropuncture techniques. Canalicular cells, which
      secrete the primary urine, function as a Cl(-)-secreting epithelium. An apical Cl
      conductance contributes to the lumen-negative potential which drives
      transcellular K+ transport and paracellular Na+ transport. On the basolateral
      side, a ouabain-sensitive Na+/K(+)-ATPase contributes substantially to the
      cellular and transcellular potential and provides the Na+ gradient necessary for
      a bumetanide-sensitive Na+/K+/2Cl- cotransport. Final urine is formed by
      subsequent reabsorption of ions along the central canal, where KCl and NaCl are
      reabsorbed in different portions. The postprandial diuresis is not a consequence
      of the changes in blood osmolality or ion concentrations. Similar changes in the
      ionic environment do not promote diuresis in isolated nephridia. Apparently, the
      composition and volume of the primary urine cannot be separately controlled. Any
      increase in fluid secretion by leech canalicular cells involves upregulation of
      the paracellular pathway and stimulation of Cl- entry, which thereby changes the
      normally K(+)-enriched primary urine to the Na(+)-enriched primary urine
      characteristic of leeches in diuresis.

PMID- 9286104
TI  - Molecular and cytogenetic analyses of stably and unstably expressed transgene
      loci in tobacco.
AB  - To study the influence of genomic context on transgene expression, we have
      determined the T-DNA structure, flanking DNA sequences, and chromosomal location
      of four independent transgene loci in tobacco. Two of these loci were stably
      expressed in the homozygous condition over many generations, whereas the other
      two loci became unstable after several generations of homozygosity. The stably
      expressed loci comprised relatively simple T-DNA arrangements that were flanked
      on at least one side by plant DNA containing AT-rich regions that bind to nuclear
      matrices in vitro. Of the unstably expressed loci, one consisted of multiple
      incomplete T-DNA copies, and the second contained a single intact T-DNA; in both
      cases, however, binary vector sequences were directly contiguous to a right T-DNA
      border. Fluorescence in situ hybridization demonstrated that the two stably
      expressed inserts were present in the vicinity of telomeres. The two unstably
      expressed inserts occupied intercalary and paracentromeric locations,
      respectively. Results on the stability of transgene expression in F1 progeny
      obtained by intercrossing the four lines and the sensitivity of the four
      transgene loci to inactivation in the presence of an unlinked "trans-silencing"
      locus are also presented. The findings are discussed in the context of repetitive
      DNA sequences and the allotetraploid nature of the tobacco genome.

PMID- 9286105
TI  - The ABSCISIC ACID-INSENSITIVE3, FUSCA3, and LEAFY COTYLEDON1 loci act in concert
      to control multiple aspects of Arabidopsis seed development.
AB  - Previous studies have shown that recessive mutations at the Arabidopsis ABSCISIC
      ACID-INSENSITIVE3 (ABI3), FUSCA3 (FUS3), and LEAFY COTYLEDON1 (LEC1) loci lead to
      various abnormalities during mid-embryogenesis and late embryogenesis. In this
      study, we investigated whether these loci act in independent regulatory pathways
      or interact in controlling certain facets of seed development. Several
      developmental responses were quantified in abi3, fus3, and lec1 single mutants as
      well as in double mutants combining either the weak abi3-1 or the severe abi3-4
      mutations with either fus3 or lec1 mutations. Our data indicate that ABI3
      interacts genetically with both FUS3 and LEC1 in controlling each of the
      elementary processes analyzed, namely, accumulation of chlorophyll and
      anthocyanins, sensitivity to abscisic acid, and expression of individual members
      of the 12S storage protein gene family. In addition, both FUS3 and LEC1 regulate
      positively the abundance of the ABI3 protein in the seed. These results suggest
      that in contrast to previous models, the ABI3, FUS3, and LEC1 genes act
      synergistically to control multiple elementary processes during seed development.

PMID- 9286106
TI  - Evolution of the rice Xa21 disease resistance gene family.
AB  - The rice disease resistance gene Xa21, encoding a receptor-like kinase, is a
      member of a multigene family. Sequence analysis of seven family members revealed
      two distinct classes of genes. One member from each class encodes a receptor
      kinase-like open reading frame. The other five members encode truncated open
      reading frames of the predicted receptor kinase. A highly conserved 233-bp
      sequence (HC) was also identified among the seven family members. Recombination
      at the HC region between family members apparently resulted in the precise
      swapping of promoter regions. Large sequence duplications were generated by a
      presumed unequal crossover event in intergenic regions. Insertions of transposon
      like sequences truncated two of the predicted open reading frames. A model for
      amplification and diversification of the Xa21 gene family is presented.

PMID- 9286107
TI  - A gene fusion at a homeobox locus: alterations in leaf shape and implications for
      morphological evolution.
AB  - Compound leaves are seen in many angiosperm genera and are thought to be either
      fundamentally different from simple leaves or elaborations of simple leaves. The
      knotted1-like homeobox (knox) genes are known to regulate plant development. When
      overexpressed in homologous or heterologous species, this family of genes can
      cause changes in leaf morphology, including excessive leaf compounding in tomato.
      We describe here an instance of a spontaneously arisen fusion between a gene
      encoding a metabolic enzyme and a homeodomain protein. We show that the fusion
      results in overexpression of the homeodomain protein and a change in morphology
      that approximates the changes caused by overexpression of the same gene under the
      control of the cauliflower mosaic virus 35S promoter in transgenic plants. Exon
      shuffling events can account for the modularity of proteins. If the shuffled
      exons are associated with altered promoters, changes in gene expression patterns
      can result. Our results show that gene fusions of this nature can cause changes
      in expression patterns that lead to altered morphology. We suggest that such
      phenomena may have played a role in the evolution of form.

PMID- 9286108
TI  - Regulation of lysine catabolism through lysine-ketoglutarate reductase and
      saccharopine dehydrogenase in Arabidopsis.
AB  - In plant and mammalian cells, excess lysine is catabolized by a pathway that is
      initiated by two enzymes, namely, lysine-ketoglutarate reductase and saccharopine
      dehydrogenase. In this study, we report the cloning of an Arabidopsis cDNA
      encoding a bifunctional polypeptide that contains both of these enzyme activities
      linked to each other. RNA gel blot analysis identified two mRNA bands-a large
      mRNA containing both lysine-ketoglutarate reductase and saccharopine
      dehydrogenase sequences and a smaller mRNA containing only the saccharopine
      dehydrogenase sequence. However, DNA gel blot hybridization using either the
      lysine-ketoglutarate reductase or the saccharopine dehydrogenase cDNA sequence as
      a probe suggested that the two mRNA populations apparently are encoded by the
      same gene. To test whether these two mRNAs are functional, protein extracts from
      Arabidopsis cells were fractionated by anion exchange chromatography. This
      fractionation revealed two separate peaks-one containing both coeluted lysine
      ketoglutarate reductase and saccharopine dehydrogenase activities and the second
      containing only saccharopine dehydrogenase activity. RNA gel blot analysis and in
      situ hybridization showed that the gene encoding lysine-ketoglutarate reductase
      and saccharopine dehydrogenase is significantly upregulated in floral organs and
      in embryonic tissues of developing seeds. Our results suggest that lysine
      catabolism is subject to complex developmental and physiological regulation,
      which may operate at gene expression as well as post-translational levels.

PMID- 9286109
TI  - A deletion in the PHYD gene of the Arabidopsis Wassilewskija ecotype defines a
      role for phytochrome D in red/far-red light sensing.
AB  - The PHYD gene of the Wassilewskija (Ws) ecotype of Arabidopsis contains a 14-bp
      deletion (the phyD-1 mutation) beginning at amino acid 29 of the reading frame,
      resulting in translation termination at a nonsense codon 138 nucleotides
      downstream of the deletion end point. Immunoblot analyses showed that Ws lacks
      phyD but contains normal levels of phyA, phyB, and phyC. By backcrossing into the
      Ws and Landsberg erecta genetic backgrounds, we constructed sibling pairs of
      PHYD+ and phyD-1 lines and of phyB- PHYD+ and phyB- phyD- lines. Hypocotyl
      lengths after growth under white or red light increased sequentially in strains
      that were B+D+, B+D-, B-D+, and B-D-. In the Ws genetic background, an increase
      in petiole length, a reduction in cotyledon area and in anthocyanin accumulation
      in seedling stems, a diminished effect of an end-of-day pulse of far-red light on
      hypocotyl elongation, and a decrease in the number of rosette leaves at the onset
      of flowering were also seen sequentially in these lines. Thus, phyD, which is
      approximately 80% identical in amino acid sequence to phyB, acts in conjunction
      with phyB in regulating many shade avoidance responses. The existence of the
      apparently naturally occurring phyD-1 mutation indicates that phyD is not
      essential in some natural environments.

PMID- 9286110
TI  - FPF1 promotes flowering in Arabidopsis.
AB  - We have characterized the gene flowering promoting factor1 (FPF1), which is
      expressed in apical meristems immediately after the photoperiodic induction of
      flowering in the long-day plants mustard and Arabidopsis. In early transition
      stages, expression is only detectable in the peripheral zone of apical meristems;
      however, later on, it can also be found in floral meristems and in axillary
      meristems that form secondary inflorescences. The FPF1 gene encodes a 12.6-kD
      protein that has no homology to any previously identified protein of known
      function. Constitutive expression of the gene in Arabidopsis under control of the
      cauliflower mosaic virus 35S promoter resulted in a dominant heritable trait of
      early flowering under both short- and long-day conditions. Treatments with
      gibberellin (GA) and paclobutrazol, a GA biosynthesis inhibitor, as well as
      crosses with GA-deficient mutants indicate that FPF1 is involved in a GA
      dependent signaling pathway and modulates a GA response in apical meristems
      during the transition to flowering.

PMID- 9286112
TI  - Mendel's stem length gene (Le) encodes a gibberellin 3 beta-hydroxylase.
AB  - We describe the isolation of the Le gene of pea, which controls internode
      elongation and originally was described by Mendel. Heterologous screening of a
      pea cDNA library yielded a partial clone that was 61% identical to coding regions
      of the putative Arabidopsis gibberellin 3 beta-hydroxylase gene, GA4. DNA gel
      blot analysis with this cDNA revealed a HindIII restriction fragment length
      polymorphism between pea isolines differing at Mendel's Le locus. Genomic clones
      of the GA4-related gene were isolated from the Le and le isolines. Polymerase
      chain reaction combined with restriction fragment length polymorphism analysis
      were used to show that the gene mapped to the Le locus. A cDNA containing a
      complete open reading frame of the pea GA4-related gene was amplified by
      polymerase chain reaction from each isoline. Recombinant expression in
      Escherichia coli demonstrated that the product of the Le cDNA was a gibberellin 3
      beta-hydroxylase that is able to convert GA20 to the bioactive GA1. Substantially
      reduced levels of gibberellin 3 beta-hydroxylase activity were measured, after
      expression of the le cDNA, by using identical methods. This reduced activity was
      associated with an alanine-to-threonine substitution in the predicted amino acid
      sequence of the enzyme near its proposed active site.

PMID- 9286111
TI  - Nitrogen assimilation in alfalfa: isolation and characterization of an asparagine
      synthetase gene showing enhanced expression in root nodules and dark-adapted
      leaves.
AB  - Asparagine, the primary assimilation product from N2 fixation in temperate
      legumes and the predominant nitrogen transport product in many plant species, is
      synthesized via asparagine synthetase (AS; EC 6.3.5.4). Here, we report the
      isolation and characterization of a cDNA and a gene encoding the nodule-enhanced
      form of AS from alfalfa. The AS gene is comprised of 13 exons separated by 12
      introns. The 5' flanking region of the AS gene confers nodule-enhanced reporter
      gene activity in transformed alfalfa. This region also confers enhanced reporter
      gene activity in dark-treated leaves. These results indicate that the 5' upstream
      region of the AS gene contains elements that affect expression in root nodules
      and leaves. Both AS mRNA and enzyme activity increased approximately 10- to 20
      fold during the development of effective nodules. Ineffective nodules have
      strikingly reduced amounts of AS transcript. Alfalfa leaves have quite low levels
      of AS mRNA and protein; however, exposure to darkness resulted in a considerable
      increase in both. In situ hybridization with effective nodules and beta
      glucuronidase staining of nodules from transgenic plants showed that AS is
      expressed in both infected and uninfected cells of the nodule symbiotic zone and
      in the nodule parenchyma. RNA gel blot analysis and in situ hybridization results
      are consistent with the hypothesis that initial AS expression in nodules is
      independent of nitrogenase activity.

PMID- 9286114
TI  - Cloning and expression of a gibberellin 2 beta,3 beta-hydroxylase cDNA from
      pumpkin endosperm.
AB  - A cDNA expression library in lambda MOSEIox derived from poly(A)+ RNA from
      pumpkin endosperm was screened immunologically with a polyclonal antibody raised
      against partially purified gibberellin (GA) 2 beta,3 beta-hydroxylase from
      pumpkin endosperm. A recombinant fusion protein encoded by a selected positive
      clone catalyzed 3 beta-hydroxylation of GA15, GA24, GA25, and GA17 and of GA12
      aldehyde, GA12, GA9, and GA20, albeit less efficiently. The fusion protein also
      catalyzed 2 beta-hydroxylation of the C20 GAS GA25, GA13, and, as identified
      putatively, GA28. The full-length clone contains an open reading frame of 1041
      nucleotides encoding 346 amino acid residues with a predicted molecular weight of
      38,992 and pI of 7.2. Transcript levels of this gene and of the previously cloned
      GA 7-oxidase and 20-oxidase genes from pumpkin endosperm rose until day 2 after
      the start of imbibition of the mature seeds, but only at one-two hundredth to one
      six thousandth of the level found in the endosperm, as determined by quantitative
      reverse transcriptase-polymerase chain reaction. In contrast, GA 7-oxidase, 20
      oxidase, and 3 beta-hydroxylase enzyme activities were present in cell-free
      systems prepared from embryos of mature seeds and decreased after imbibition.

PMID- 9286117
TI  - Outcome of patients with neurally mediated syncope following tilt table testing.

PMID- 9286115
TI  - S2F, a leaf-specific trans-acting factor, binds to a novel cis-acting element and
      differentially activates the RPL21 gene.
AB  - Tissue-specific factors control the differential expression of nuclear genes
      encoding plastid proteins. To identify some of these factors, the light
      independent spinach RPL21 gene encoding the plastid ribosomal protein L21 was
      chosen as a model. The RPL21 promoter organization was defined by transient and
      stable transfections of RPL21 promoter deletion mutants fused to a reporter gene.
      The following results were obtained. (1) We identified a strong core promoter,
      spanning the transcription start site region, sufficient to drive high levels of
      gene expression. (2) We identified two non-overlapping positive and negative
      domains, located upstream from the core promoter region, that modulate core
      promoter activity independently of light. (3) We found that the positive domain
      contains a new cis-acting element, the S2 site, related to but different from the
      light-responsive GT-1 binding site. We show that the S2 site binds a leaf
      specific nuclear factor (named S2F). The S2 site is conserved in the promoter
      region of many nuclear genes encoding plastid proteins. Experiments with
      transgenic tobacco plants confirmed that the S2 site is critical for positive
      domain activity in leaf tissues. The S2 site is thus identified as a new tissue
      specific, light-independent regulatory element.

PMID- 9286119
TI  - Cytogenetic aspects of cell proliferation in atherosclerotic plaques.
AB  - Fluorescence in situ hybridization (FISH) using chromosome specific alpha
      satellite DNA probes for chromosome 7, was performed on paraffin-embedded
      sections of 21 cases of human "unstable" atherosclerotic plaques, in order to
      determine whether trisomy 7, found by some Authors with conventional
      cytogenetics, is a biological characteristic of the atherosclerotic plaque. In 15
      cases (71%) the FISH method showed smooth muscle cells with three or more spots.
      In particular the trisomy 7 was the most significant and constant result. The
      presence of an extra chromosome 7 is strictly correlated with an overexpression
      of the gene for chain A of the platelet-derived growth factor (PDGF), which was
      mapped at pter-7q22 region. Therefore trisomy 7 seems to correspond to an
      increase in PDGF synthesis and consequently to an increase in proliferative
      activity of smooth muscle cells.

PMID- 9286118
TI  - Angioscopy of culprit lesions.

PMID- 9286116
TI  - Role of the proline knot motif in oleosin endoplasmic reticulum topology and oil
      body targeting.
AB  - An Arabidopsis oleosin was used as a model to study oleosin topology and
      targeting to oil bodies. Oleosin mRNA was in vitro translated with canine
      microsomes in a range of truncated forms. This allowed proteinase K mapping of
      the membrane topology. Oleosin maintains a conformation with a membrane
      integrated hydrophobic domain flanked by N- and C-terminal domains located on the
      outer microsome surface. This is a unique membrane topology on the endoplasmic
      reticulum (ER). Three universally conserved proline residues within the "proline
      knot" motif of the oleosin hydrophobic domain were substituted by leucine
      residues. After in vitro translation, only minor differences in proteinase K
      protection could be observed. These differences were not apparent in soybean
      microsomes. No significant difference in incorporation efficiency on the ER was
      observed between the two oleosin forms. However, as an oleosin-beta-glucuronidase
      translational fusion, the proline knot variant failed to target to oil bodies in
      both transient embryo expression and in stably transformed seeds. Fractionation
      of transgenic embryos expressing oleosin-beta-glucuronidase fusions showed that
      the proline knot variant accumulated in the ER to similar levels compared with
      the native form. Therefore, the proline knot motif is not important for ER
      integration and the determination of topology but is required for oil body
      targeting. The loss of the proline knot results in an intrinsic instability in
      the oleosin polypeptide during trafficking.

PMID- 9286120
TI  - AIDS and HIV infection in the United Kingdom: monthly report.

PMID- 9286121
TI  - Typhoid fever associated with travel to the Dominican Republic.

PMID- 9286123
TI  - Suicide in late life at the end of the 1990s: a less neglected topic?

PMID- 9286122
TI  - Inpatients under constant observation for suicide risk.

PMID- 9286124
TI  - The discrete charm of the hotline.

PMID- 9286125
TI  - Elderly suicides in Hong Kong: the role of volunteer befrienders.

PMID- 9286126
TI  - Another preventable jail suicide.

PMID- 9286127
TI  - Letter across the Pacific.

PMID- 9286128
TI  - Individual therapy techniques with adolescent suicide attempters.

PMID- 9286129
TI  - Support in suicidal crises: the Swedish National Program to Develop Suicide
      Prevention. The Swedish National Council for Suicide Prevention.
AB  - The Swedish National Program to Develop Suicide Prevention was created through
      collaboration between the National Board of Health and Welfare, the National
      Institute of Public Health, and the Centre for Suicide Research and Prevention.
      These institutions aim to provide joint support for the development of suicide
      prevention in Sweden by, for example, encouraging educational and development
      project. The program was signed for the National Council for Suicide Prevention
      by Agneta Dreber, Director-General, National Institute of Public Health; Danula
      Wasserman, Professor of Psychiatry and Suicidology, Head, National Centre for
      Suicide Research and Prevention; and Claes Ortendahl, Director-General, National
      Board of Health and Welfare. This article, edited by Jan Beskow, Professor of
      Psychiatry at the Centre for Suicide Research and Prevention, is an abridged
      version submitted to Crisis at the request of the Editors.

PMID- 9286130
TI  - Cybersuicide: the role of interactive suicide notes on the Internet.
AB  - As we approach the new millennium a new dimension in interactive communications
      has arrived. The internet is one such medium, and while it remains a relatively
      new form of information sharing, it has not escaped the attention of vulnerable
      young people. This paper discusses the internet resources on suicide and the
      issue of interactive suicide notes. Case examples of interactive notes followed
      by suicide fatalities are used to illustrate the potential influence of the
      internet on those who wish to share their suicidal ideation with others. Issues
      to do with modeling, ambivalence, group death wishes, research, and ethics are
      discussed. Finally, some recommendations are made for further studies.

PMID- 9286131
TI  - Short-term outcome following referral to a psychiatric emergency service.
AB  - The study described here is part of an evaluation of a pilot project concerning
      the implementation of three psychiatric crisis units in general hospitals in
      Belgium. The purpose was to evaluate the short-term outcome of a
      multidisciplinary crisis intervention for psychiatric patients referred to the
      emergency department. Patients were assessed with the General Health
      Questionnaire (GHQ-28) at the time of referral to the emergency department and
      again 1 month later. Patients referred for a psychiatric crisis intervention were
      compared with patients receiving short-term psychiatric inpatient treatment in
      another hospital. Patients referred to the emergency department showed a
      considerable degree of psychiatric disturbance. The General Health Questionnaire
      appeared to be a good measure for assessment of the "state" aspect of a
      psychiatric disturbance. The state of distress was significantly reduced one
      month after referral in both treatment conditions. Nevertheless, an important
      proportion of patients remained in a state of considerable distress. The results
      indicate that a short hospital-based crisis intervention approach is comparable
      with more traditional acute inpatient treatment. However, in the case of more
      severely distressed patients it may be insufficient. Several limitations of this
      study are also discussed (risk of overestimation of improvement, influence of
      time or pre-existing differences).

PMID- 9286132
TI  - The relationship between stressful and traumatic life events and depression in
      the elderly.

PMID- 9286133
TI  - The Irish Association of Suicidology arrives--conference report: "suicide in
      ireland: a growing problem".

PMID- 9286134
TI  - Suicide prevention: the global context.

PMID- 9286135
TI  - Task force meeting on euthanasia.

PMID- 9286136
TI  - Norman Farberow Award, 1997. Onja Grad, PhD.

PMID- 9286137
TI  - Erwin Stengel Award 1997. Armin Schmidtke, PhD.

PMID- 9286138
TI  - Erwin Ringel Award, 1997. Rev. Yukio Saito.

PMID- 9286139
TI  - Letter to the editors on "Negative effects of a school suicide postvention
      program--a case example".

PMID- 9286140
TI  - Market medicine.

PMID- 9286141
TI  - Antithrombotic treatment in chronic non-rheumatic atrial fibrillation.

PMID- 9286142
TI  - Diagnostic criteria of the myeloproliferative disorders (MPD): essential
      thrombocythaemia, polycythaemia vera and chronic megakaryocytic granulocytic
      metaplasia.
AB  - Philadelphia chromosome-positive essential thrombocythaemia (Ph(+)-ET) and
      chronic granulocytic leukaemia (Ph(+)-CGL) constitute a separate malignant
      disease entity, whereas essential thrombocythaemia (ET), polycythaemia vera (PV)
      and chronic megakaryocytic granulocytic metaplasia (CMGM) belong to the
      Philadelphia chromosome-negative (Ph-) myeloproliferative disorders. The
      megakaryocytes in Ph(+)-ET and Ph(+)-CGL are abnormal and small with round
      nuclei, showing little lobulation. Both the number and size of megakaryocytes in
      Ph-ET, -PV and -CMGM are typically increased. Enlarged megakaryocytes with mature
      cytoplasm and multilobulated nuclei and their tendency to cluster in a normal or
      slightly increased cellular bone marrow represent the hallmark of ET. In reactive
      thrombocytosis the size and morphology of increased megakaryocytes are normal.
      The characteristic increase and clustering of enlarged mature and pleomorphic
      megakaryocytes with multilobulated nuclei and proliferation of erythropoiesis in
      a moderate to marked hypercellular bone marrow with hyperplasia of dilated
      sinuses is the diagnostic hallmark of untreated PV. In secondary polycythaemia,
      in which increased cellularity of the erythroid cell line may be present, the
      number, size and morphology of megakaryocytes remain small and normal. CMGM,
      including early stages without myelofibrosis and advanced myelofibrotic stages of
      agnogenic myeloid metaplasia, appears to be a distinct neoplastic proliferation
      of neutrophilic granulopoiesis and megakaryopoiesis. The histopathology of the
      bone marrow in CMGM is dominated by atypical, enlarged and immature
      megakaryocytes with cloud-like nuclei which are not seen in ET and PV.
      Myelofibrosis in ET, PV and CMGM is graded in no reticulin fibrosis (MFO), early
      reticulin fibrosis (MF1), advanced reticulin sclerosis with minor collagen
      fibrosis (MF2) and advanced collagen fibrosis with or without osteosclerosis
      (MF3). Myelofibrosis is not a feature of ET, may occur in PV, and constitutes a
      prominent feature of CMGM during the natural history of the disease.

PMID- 9286143
TI  - Prognostic and predictive factors in breast cancer.

PMID- 9286144
TI  - Cerebellitis as an uncommon complication of infectious mononucleosis.
AB  - Cerebellitis is an uncommon complication of infectious mononucleosis. We describe
      such a patient with infectious mononucleosis and cerebellitis as a major feature
      of a more global encephalitis. In the discussion the cerebral complications are
      reviewed.

PMID- 9286146
TI  - Thymic tuberculosis: a case report.
AB  - Tuberculosis of the thymus is an extremely rare diagnosis, only three cases
      having been reported in the literature to date. Clinical, roentgenographic and
      histopathological findings are presented in a 29-year-old woman. The patient
      underwent sternotomy for a mediastinal mass suspected to be a thymoma, which was
      histopathologically diagnosed as thymic tuberculosis.

PMID- 9286147
TI  - Preschool development. 1: Communicative and motor aspects.

PMID- 9286145
TI  - Management of Salmonella infections during pregnancy and puerperium.
AB  - The case history of a neonatal infection caused by Salmonella enteritidis group D
      is presented. The mother suffered from gastroenteritis 1 week ante partum. The
      newborn was treated with ampicillin, gentamicin and later amoxicillin but 5
      months later was still a carrier of Salmonella. The possible route of infection
      and the guidelines for therapy and management of Salmonella infections during
      pregnancy and puerperium are discussed.

PMID- 9286148
TI  - Nephropathic cystinosis.
AB  - Nephropathic cystinosis is one of the only lysosomal storage diseases for which
      there is an effective therapy against the basic, pathologic process-cystine
      accumulation. Early diagnosis and therapy are critical to optimize the prognosis.

PMID- 9286149
TI  - Methamphetamine.

PMID- 9286150
TI  - Recurrent abdominal pain: an update.
AB  - RAP is a broad descriptive term commonly used in pediatrics to define a
      heterogeneous group of patients who experience episodic attacks of abdominal pain
      over a period of at least 3 months. The majority of patients who seek medical
      attention for RAP have a functional disorder thought to be triggered by a
      motility or sensory disturbance of the GI tract provoked by a variety of physical
      and psychological stimuli. There are three distinct clinical presentations of
      functional abdominal pain in children and adolescents: periumbilical paroxysmal
      abdominal pain, dyspepsia, and irritable bowel. The medical history, physical
      examination, and selected laboratory, radiologic, and endoscopic evaluations
      allow a positive diagnosis of a functional disorder in each type of clinical
      presentation.

PMID- 9286151
TI  - Circadian variation of skin perfusion in arterial occlusive disease.
AB  - BACKGROUND: Many physiological processes are subjected to circadian variation. We
      tested if circadian changes of skin perfusion can be detected by measuring laser
      Doppler flux (LDF) in the foot and if such variations are different in patients
      with peripheral arterial occlusive disease (PAOD). PATIENTS AND METHODS: LDF was
      recorded hourly during a 24-hour period in 10 healthy subjects and in 19 PAOD
      patients, 9 presenting with claudication (stage II according to Fontaine, ankle
      artery pressures (AP) 80 +/- 11 mmHg) and 10 with skin necrosis (stage IV, AP 42
      +/- 29 mmHg). RESULTS: Circadian variability of LDF was significantly reduced in
      stage IV patients compared both with stage II patients and controls (p < 0.01).
      An increase in LDF could be observed early in the afternoon and, more pronounced,
      during the night, occurring to the same extent in healthy and PAOD patients in
      stage II (p < 0.001). In stage IV the increase in LDF was not significant and a
      decrease was observed in two patients. LDF and local skin temperature were
      correlated in controls and stage II patients (mean r = 0.69 +/- 0.12 and 0.7 +/-
      0.14, respectively), but not in stage IV (mean r = 0.23 +/- 0.18). A further
      limitation of LDF variability and nocturnal increase was seen in the presence of
      diabetes. CONCLUSION: Circadian variations of skin blood flow are comparable in
      controls and patients with claudication but markedly reduced in patients with
      severe PAOD presenting with ulcers, in whom skin perfusion seems uncoupled from
      temperature regulation, possibly due to local factors causing continuous
      arteriolar vasodilation.

PMID- 9286152
TI  - Changes of dermal haemoglobin oxygenation and concentration in healthy subjects
      and in patients with peripheral arterial occlusive disease during and after acute
      ischemia.
AB  - BACKGROUND: Oxygen saturation (SHB) and concentration (CHB) of dermal haemoglobin
      play an important role in the nutrition of the skin. In patients with severe
      peripheral arterial occlusive disease (PAOD) they are reduced at the forefoot. We
      investigated the changes of the named parameters during an acute ischemia and
      during reactive hyperemia using an occlusion test. PATIENTS AND METHODS: Dermal
      reflection spectra were conducted from the forefoot of 11 healthy subjects and 39
      patients with peripheral arterial occlusive disease of various stages at rest,
      during, and after an arterial occlusion at the thigh. Using a multicomponent
      analysis SHB and CHB were calculated iteratively. The halftime of the post
      occlusive increase of SHB (post-occlusive recovery halftime PORHT) and the
      relation of post- to pre-occlusive CHB (post-occlusive reactive hyperemia PORH)
      were calculated to estimate the dynamic of the post-occlusive inflow of blood.
      TcPO2 (37 degrees C) was additionally determined at the forefoot. RESULTS: In
      patients from stage III and IV all resting values were lower compared to
      controls. TcPO2 decreased in all persons to 0 mm Hg during the occlusion, SHB was
      between 0 and 10%, while CHB remained unchanged. In healthy subjects and in
      patients with claudication the post-occlusive values exceeded the preocclusive
      ones, while in some patients with higher stages of the disease this could not be
      found. There was a marked, on the stage of the disease depending difference in
      the post-occlusive course between controls and patients: in healthy subjects it
      took only 5.5 +/- 4.8 s until SHB reached half of the maximum value, in patients
      from the stage IIa group 26.8 +/- 16.9 s (p < 0.001) was measured while in stage
      III and IV the value was 132 +/- 75 s (p < 0.001). CONCLUSIONS: During ischemia a
      decrease of the haemoglobin oxygen saturation (SHB) and tcPO2 was found.
      Haemoglobin concentration (CHB) remained constant, hence a significant shift of
      blood from skin to muscle did not take place. PORHT was selectively dependent on
      the stage of the disease. The occlusion manoeuvre enhances the significance of
      reflection photometry in PAOD.

PMID- 9286153
TI  - Nailfold capillaroscopy and laser Doppler fluxmetry for evaluation of Raynaud's
      phenomenon: how valid is the local cooling test?
AB  - BACKGROUND: Since there is a need for an objective parameter of microcirculation
      in follow-up of patients with Raynaud's syndrome we evaluated the reproducibility
      of the reaction to a cold exposure test with nailfold capillaroscopy and laser
      Doppler fluxmetry during a winter period. PATIENTS AND METHODS: 10 healthy
      subjects and 16 patients with primary Raynaud's syndrome were evaluated with
      nailfold capillaroscopy and laser Doppler fluxmetry of the finger tips during and
      after a standardized cold exposure stress test. The measurements were repeated in
      the controls within 2 weeks, in the patient population twice within 24 weeks.
      RESULTS: In the healthy controls the percentage of capillaries with flow stop was
      stable (r = 0.785) and the duration of flow stop was reproducible (r = 0.993).
      Both parameters were significantly lower in controls than in the patients. The
      flow stop durations in patients varied intra-individually to a great extent
      between the different weeks without any significant correlation. For all
      calculated laser Doppler perfusion and time parameters we did not find any
      significant differences between controls and patients nor any consistent
      correlations in the intra-individual comparison within the different weeks for
      both, controls and patients. CONCLUSION: Nailfold capillaroscopy during cold
      exposure is able to discriminate between healthy persons and patients with
      primary Raynaud's syndrome, but seems to be of minor value for follow-up
      evaluation of patients because of intraindividual variations. Laser Doppler
      fluxmetry is invalid for both purposes when using the applied cold exposure test.

PMID- 9286154
TI  - Blood flow velocity measurements for carotid stenosis estimation: interobserver
      variation and interequipment variability.
AB  - BACKGROUND: Because of the wide range of recommended threshold values for carotid
      stenosis graduation we performed a prospective study to determine interobserver
      and interequipment variability of quantitative blood flow velocity measurements.
      PATIENTS AND METHODS: We recorded absolute blood flow velocities and velocity
      ratios in 21 patients with carotid artery stenosis using two colour coded duplex
      ultrasound systems an ATL Ultramark 9 HDI, and a Hewlett Packard SONOS 2500
      system. The ATL system was used for the interobserver variation study, where each
      patient was examined twice on the same day. The Doppler angle was recorded
      together with blood flow velocities (peak systolic velocity and mean maximum
      velocity from the velocity-time-integral both in the stenosis jet and 4-5 cm
      distally in the cranial portion of the internal carotid artery off poststenotic
      turbulences). RESULTS: The ATL system generated significantly higher blood flow
      velocity values as compared with the HP system (218 +/- 156 cm/s vs. 169 +/- 114
      cm/s; p < 0.001). The Mean Velocity Ratio (the ratio of intrastenotic Vmean and
      poststenotic Vmean) was constant with both duplex systems. The HP system yielded
      10% (Cl, 7-13%) lower predicted stenosis estimates than the ATL system with Vmax
      as the stenosis criterion. The stenosis estimates calculated from Mean Velocity
      Ratio values did not differ significantly. The 95% Cl for predicted diameter
      reduction between two observer was 13.6% (Vmax) and 15.4% (Mean Velocity Ratio).
      CONCLUSION: Because of significant interequipment differences of colour coded
      duplex ultrasound systems we recommend calculation of the Mean Velocity Ratio to
      avoid interpatient and interequipment variation of absolute flow velocities.
      According to our interobserver variability study, a change of more than 15%
      diameter reduction on follow-up examinations indicates disease progression or
      regression.

PMID- 9286155
TI  - Classification of Sneddon's syndrome.
AB  - BACKGROUND: The combination of generalized broken ("racemose") livedo and
      cerebrovascular accidents is referred to as "Sneddon's syndrome". Although
      several pathogenetic factors have been suggested the aetiology of Sneddon's
      syndrome is unknown. Furthermore, considerable variability of patient
      characteristics gives rise to the question whether "Sneddon's syndrome" denotes a
      homogeneous disease entity at all. We hypothesized that the diagnosis "Sneddon's
      syndrome" can be broken down into different subgroups according to possible
      aetiologic factors. PATIENTS AND METHODS: Thirty-two patients with the
      combination of generalized broken livedo and cerebrovascular accidents were
      evaluated by clinical examination, routine diagnostic procedures, MRI of the
      brain, echocardiography, vascular ultrasound, immunologic and haemostaseologic
      testing. Patient groups were formed, depending on (1) whether or not an
      additional feature with a possibly aetiologic role for Sneddon's syndrome was
      present, and (2) which kind of feature it was. RESULTS: In 16 out of 32 patients,
      diagnostic features with an implication for the pathogenesis of Sneddon's
      syndrome could be identified. An autoimmune disorder was diagnosed in six
      patients. A thrombophilic state was detected in six patients. Three patients had
      preexisting atherosclerosis. One patient suffered from an embolizing atrial
      myxoma. Extent and kind of cerebral pathology differed between patient groups as
      did the kind of cardiac involvement. CONCLUSION: Sneddon's syndrome is not a
      homogeneous disease entity. Patients should be classified as "primary Sneddon's
      syndrome" if no aetiologic factor can be detected. On clinical grounds, this from
      differs from several varieties of "secondary Sneddon's syndrome" which occurs
      mainly as part of an autoimmune disorder or in a thrombophilic state.

PMID- 9286156
TI  - Report of general temporary anticoagulation in the treatment of acute cerebral
      and retinal ischaemia.
AB  - BACKGROUND: Recurrent thrombo-embolism represents by far the commonest cause of
      cerebral and retinal ischaemia. In an open clinical study, experience with a
      largely general anticoagulation in the acute phase of cerebral and retinal
      ischaemia is reported. METHODS: From October 1993 to October 1996, 781 patients
      with acute cerebral ischaemia were admitted to the medical emergency ward. Taking
      contra-indications into consideration and after CT exclusion of cerebral
      haemorrhage (2%). Immediate therapeutic heparinisation (1.5-2-fold prolongation
      of aPTT) was administered to 664 patients (85%) over 7-10 days. In a concurrent
      Doppler/duplex comparative study, 143 patients with retinal artery occlusion were
      investigated for the prevalence of potential sources of emboli in the region of
      the extracranial carotids and internal carotid circulation respectively. 108
      patients served as a reference group whose acute loss of vision of vascular
      origin could be attributed to retinal vein thrombosis. RESULTS: The complication
      rate of anticoagulation in acute cerebral ischaemia was 0.8% (major
      complications), and the recurrence rate during the period of treatment was 2.4%.
      In 131 patients with acute retinal ischaemia, therapeutic heparinisation was
      performed without ocular cerebral or extracerebral complications. Potential
      ipsilateral sources of emboli (highgrade carotid stenosis or complex plaques with
      thrombotic deposits) were found in 55%, but in only 7% of the control group (p <
      0.0001). CONCLUSION: Immediate anticoagulation in the form of aPTT-monitored
      therapeutic heparinisation represents a rational and low-risk concept for the
      treatment of acute cerebral and retinal ischaemia.

PMID- 9286158
TI  - Pushing down the limits of detection: molecular needles in a haystack.

PMID- 9286157
TI  - Organic SIMS of biologic tissue.

PMID- 9286159
TI  - Microchip device for performing enzyme assays.
AB  - An automated enzyme assay was performed within a microfabricated channel network.
      Precise concentrations of substrate, enzyme, and inhibitor were mixed in
      nanoliter volumes using electrokinetic flow. Reagent dilution and mixing were
      controlled by regulating the applied potential at the terminus of each channel,
      using voltages derived from an equivalent circuit model of the microchip. The
      enzyme beta-galactosidase (beta-Gal) was assayed using resorufin beta-D
      galactopyranoside (RBG), a substrate that is hydrolyzed to resorufin, a
      fluorescent product. Reaction kinetics were obtained by varying the concentration
      of substrate on-chip and monitoring the production of resorufin using laser
      induced fluorescence. Derived Michaelis--Menten constants compared well between
      an on-chip and a conventional enzyme assay. Bias in the derived K(m) and kcat was
      primarily due to the limited solubility of RBG and the associated lack of
      measurements at substrate concentrations exceeding the K(m). A Ki of 8 microM for
      the inhibitor phenylethyl beta-D-thiogalactoside (PETG) was determined from plots
      of initial rate versus substrate concentration obtained at three concentrations
      of PETG. The relative inhibition of beta-Gal by lactose, p-hydroxymercuribenzoic
      acid, and PETG was determined by varying the inhibitor concentration with
      constant enzyme and substrate concentration. An enzyme assay performed on the
      microchip within a 20-min period required only 120 pg of enzyme and 7.5 ng of
      substrate, reducing the amount of reagent consumed by 4 orders of magnitude over
      a conventional assay.

PMID- 9286161
TI  - Flow injection renewable surface immunoassay for real time monitoring of
      biospecific interactions.
AB  - An automated system for performing rapid immunoassay, kinetic measurements, and
      affinity ranking of biomolecular interactions using fluorescence-labeled ligands
      is described. Its distinctive feature is the automated renewal of solid phase for
      each measurement, which avoids the need for regeneration of the sensing surface.
      This system--flow injection renewable surface immunoassay (FIRSI)--is used for
      the first time here for determination of rate constants for an antibody/antigen
      interaction and for affinity ranking of several related antigens against one
      antibody. The performance of the system is compared with a commercial BIAcore
      system that uses surface plasmon resonance for monitoring biomolecular
      interactions. While the values of association and dissociation rate constants for
      human serum albumin (HSA) with monoclonal anti-HSA antibody obtained by these
      techniques were comparable, it is shown that the FIRSI techniques requires
      simpler instrumentation, handles a broader size range of analytes, and does not
      suffer from disturbances caused by changes in the refractive index.

PMID- 9286160
TI  - Patch clamp detection in capillary electrophoresis.
AB  - We describe a capillary electrophoresis-patch clamp (CE-PC) analysis of
      biomolecules that activate ligand-gated ion channels. CE-PC offers a powerful
      means for identifying receptor ligands based on the combination of the
      characteristic receptor responses they evoke and their differential
      electrophoretic migration rates. Corner frequencies, membrane reversal
      potentials, and mean and unitary single-channel receptor responses were
      calculated from currents recorded with patch clamp detection. This information
      was then combined with the electrophoretic mobility of the receptor ligand, which
      is proportional to the charge-to-frictional-drag ratio of that species. We
      applied CE-PC to separate and detect the endogenous receptor agonists gamma
      aminobutyrate and L-glutamate and the synthetic glutamate receptor agonists N
      methyl-D-aspartate and kainic acid. We present dose-response data for
      electrophoretically separated kainic acid and discuss its implications for making
      the CE-PC detection system quantitative.

PMID- 9286162
TI  - Piezoelectric immunosensors for urine specimens of Chlamydia trachomatis
      employing quartz crystal microbalance microgravimetric analyses.
AB  - The assembly of a biosensor for Chlamydia trachomatis based on the
      microgravimetric quartz crystal microbalance (QCM) analysis of the bacteria
      association to an antibody-functionalized electrode is described. The sensing
      interfaces consist of a primary cystamine monolayer assembled onto Au electrodes
      associated with the quartz crystal. The monolayer is further modified with
      sulfosuccinylimidyl 4-(p-maleimidophenyl)butyrate (sulfo-SMPB) and the goat IgG
      anti-mouse IgG Fc-specific Ab or the fragmented F(ab')2 anti-mouse IgG Ab that
      act as sublayers for the association of the sensor-active anti-C. trachomatis LPS
      Ab. Bacteria in the concentration range from 260 ng.mL-1 to 7.8 micrograms.mL-1
      are sensed by the functionalized crystals. The association of C. trachomatis to
      the sensing interface can be confirmed and amplified via interaction of the
      crystal with various anti-C. trachomatis antibodies. Urine-pretreated
      functionalized quartz crystals are applied in the analysis of C. trachomatis in
      urine samples. The sensitivity limits of the electrodes for sensing the bacteria
      in urine samples corresponds to approximately 260 ng.mL-1. The functionalized
      crystals assembled via association of anti-C. trachomatis LPS-Ab to the
      fragmented F(ab')2 anti-mouse IgG Ab reveal long-term stability upon storage at 4
      degrees C.

PMID- 9286163
TI  - Indium as internal standard in square wave anodic stripping analysis of lead in
      blood with microelectrode arrays.
AB  - The toxic effects of lead on humans, especially children have been well
      documented. ASV has been an important technique in the analysis of lead in blood
      of humans. This research has demonstrated that indium(III) can be used as an
      internal standard in the analysis of lead in blood samples with mercury film
      microelectrode arrays. Indium is a good choice because of a low endogenous blood
      concentration and because baseline separation of anodic stripping peaks among Cd,
      In, and Pb can be achieved under appropriate conditions. The concentration of
      sodium bromide strongly influences the resolution of these metals and the
      sensitivity of ASV to In(III) in solution. Square wave anodic stripping
      voltammetry together with screen-printed microelectrode arrays showed that the
      ratio of the anodic stripping peak currents of Pb and In varies linearly with the
      concentration of Pb in blood samples ranging from 1.2 to 30.0 micrograms/dL. The
      average intraassay precision (rsd) was 6.7%.

PMID- 9286164
TI  - A flow injection microdialysis sampling chemiluminescence system for in vivo on
      line monitoring of glucose in intravenous and subcutaneous tissue fluid
      microdialysates.
AB  - A novel flow injection on-line microdialysis system for in vivo monitoring of
      glucose in subcutaneous tissue fluid and blood is described. An implantable loop
      type microdialysis probe was used for subcutaneous sampling, and a flow-through
      microdialyzer was used for intravenous sampling by pumping of the blood from the
      tested rabbit through the microdialyzer located outside the living system at a
      flow rate of 10 microL/min. The perfusion rate of the dialysate was 20
      microL/min. The glucose in the dialysate was detected on-line with a flow
      injection chemiluminescence system after passing through an immobilized glucose
      oxidase reactor. The calibration of the detector system (including reactor) and
      monitoring of baseline drifts were performed simultaneously to improve the
      reliability of the monitoring process. The dialysate sample volume was 20 microL,
      and the sample throughout was 28 h-1. The variation of glucose level in
      subcutaneous tissue fluid and blood of the rabbits was monitored after the
      administration of glucose or insulin to demonstrate the favorable resolution and
      reliability of the system for in vivo on-line monitoring.

PMID- 9286165
TI  - Electrophore mass tag dideoxy DNA sequencing.
AB  - Toward a goal of dideoxy sequencing DNA utilizing electrophore labels, we
      prepared four electrophore-labeled DNA oligonucleotide primers. Each primer has a
      different electrophore and DNA sequence but a common glycol keto (alpha,beta
      dihydroxyketo) release group. Cleavage of this latter group by either periodate
      oxidation or a thermal retroaldol reaction releases the electrophores for
      detection by mass spectrometry. Successful sequencing data with these primers was
      obtained by capillary electrophoresis on an ABI Model 310 after fluorescence
      dideoxy terminator cycle sequencing reactions were conducted. In a separate
      experiment, it was demonstrated that a cocktail of the four electrophore DNA
      primers could be detected as a dried sample spot by CO2 laser
      desorption/capillary collection/gas chromatography electron capture mass
      spectrometry. These results establish some feasibility for our long-term goal of
      high-speed multiplex electrophore mass tag dideoxy DNA sequencing. Ultimately we
      plan to use a higher number of electrophore mass tags and to rely on direct
      detection of the desorbed electrophores by electron capture time-of-flight mass
      spectrometry.

PMID- 9286166
TI  - Cryogenic frozen solution matrixes for analysis of DNA by time-of-flight mass
      spectrometry.
AB  - We present an alternative matrix system for mass analysis of high molecular
      weight biomolecules by matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry (MALDI-TOFMS). Single-stranded DNA oligomers are embedded in
      thin films of frozen solutions containing photoabsorbing substituted phenols.
      Ultraviolet laser desorption from these cryogenically cooled matrixes generates
      internally colder ions than from the equivalent room-temperature crystalline
      matrixes containing no solvent, as evidenced by a substantial reduction in the
      extent of fragmentation in the corresponding mass spectra of oligonucleotides.
      Furthermore, the homogeneity of the frozen solution samples allows analyte
      signals to be obtained uniformly throughout the sample. Sensitivity and mass
      resolution approaching that obtained using the most effective room-temperature
      crystalline matrix for DNA (3-hydroxypicolinic acid) are consistently and
      reproducibly obtained in both positive and negative ion mass spectra. As
      fragmentation is a principle factor limiting the maximum attainable mass
      resolution in MALDI-TOF mass analysis of DNA, this improvement in generating
      intact DNA ions is advantageous.

PMID- 9286167
TI  - A receptor protein-based bioassay for quantitative determination of paclitaxel.
AB  - A novel receptor-based bioassay for the quantitative measurement of Taxol was
      developed. The assay was based on the well-investigated and established finding
      that Taxol, its active analogs, and active metabolites bind reversibly to the
      receptor protein tubulin, a process similar to antibody and antigen interaction.
      The assay was performed in a competitive format by allowing a mixture of
      horseradish peroxidase-labeled Taxol and Taxol in the analyte sample to compete
      for the Taxol binding site of a polystyrene microtiter plate wall coated with
      purified tubulin and subsequently measuring the tubulin-Taxol complex by
      determining the activity of the horseradish peroxidase label. Using this method,
      Taxol was measured very sensitively, linear range of 0.0001-1 nM, and
      selectively, without interference from non-tumor-active compounds such as
      baccatin III, cephalomaninne, and 10-deacetyl taxol. The method was applied for
      the determination of picomolar concentrations of Taxol in human plasma.

PMID- 9286168
TI  - Molded rigid polymer monoliths as separation media for capillary
      electrochromatography.
AB  - Rigid, monolithic capillary columns for reversed-phase electrochromatography have
      been prepared within the confines of untreated fused-silica capillaries in a
      single step by a simple copolymerization of ethylene dimethacrylate, butyl
      methacrylate, and 2-acrylamido-2-methyl-1-propanesulfonic acid in the presence of
      a porogenic solvent. The composition of the specifically designed ternary
      porogenic solvent allows fine control of the porous properties of the monolithic
      material over a broad range. While the electroosmotic flow through these
      capillary columns increases with both increasing pore size of the monolith and
      content of charged functionalities, better chromatographic properties have been
      observed for monoliths with larger surface area and hydrophobicity. Using this
      technique, monolithic capillary columns with an efficiency higher than 120000
      plates/m have been easily obtained.

PMID- 9286169
TI  - XV FIGO World Congress of Gynecology and Obstetrics. Copenhagen, Denmark, 3-8
      August 1997. Abstracts. Part 1.

PMID- 9286170
TI  - XV FIGO World Congress of Gynecology and Obstetrics. Copenhagen, Denmark, 3-8
      August 1997. Abstracts. Part 2.

PMID- 9286171
TI  - XV FIGO World Congress of Gynecology and Obstetrics. Copenhagen, Denmark, 3-8
      August 1997. Abstracts. Part 3.

PMID- 9286172
TI  - XV FIGO World Congress of Gynecology and Obstetrics. Copenhagen, Denmark, 3-8
      August 1997. Abstracts. Part 4.

PMID- 9286173
TI  - XV FIGO World Congress of Gynecology and Obstetrics. Copenhagen, Denmark, 3-8
      August 1997. Abstracts. Part 5.

PMID- 9286174
TI  - The American Diabetic Association 80th annual meeting. Boston, Massachusetts,
      October 27-30, 1997. Abstracts.

PMID- 9286175
TI  - Progress in the science of addiction.

PMID- 9286176
TI  - Images in neuroscience. Alzheimer's disease: from genes to pathogenesis.

PMID- 9286177
TI  - Practice-based research in psychiatry.
AB  - OBJECTIVE: The authors describe the APA Practice Research Network (PRN), a
      national research initiative that ultimately will engage 1,000 practicing
      psychiatrists in collaborative clinical and services research. The PRN is
      designed to generate practice-relevant information and to inform future service
      delivery, policy, and financing decisions pertinent to psychiatry. METHOD: The
      authors review the relative strengths and limitations of practice-based research
      compared with other widely used research methods. They also describe the
      structure of the PRN and its procedures for recruiting network members and for
      identifying and developing specific network studies. The three primary sources of
      data for the PRN are 1) the biannual National Survey of Psychiatric Practice,
      which provides not only a mechanism for randomly recruiting the two-thirds of
      network participants who are not volunteers but also a baseline for assessing the
      generalizability of PRN findings; 2) separate biannual studies of psychiatric
      patients and treatments to characterize the network patient/treatment
      denominator, which is used to monitor trends in psychiatric practice and plan
      network studies; and 3) specific studies. RESULTS: Pilot data from the PRN have
      yielded detailed information on the diagnostic and clinical characteristics of
      725 patients and on the treatments provided by network psychiatrists.
      CONCLUSIONS: The APA PRN offers a powerful complement to traditional clinical and
      health services research approaches. The PRN will help psychiatry improve its
      ability to meet patients needs in a context of rapidly evolving scientific and
      clinical progress and legislative and economic forces affecting health care
      delivery.

PMID- 9286178
TI  - PET study of competition between intravenous cocaine and [11C]raclopride at
      dopamine receptors in human subjects.
AB  - OBJECTIVE: Animal data suggest that the strong euphoriant effects of cocaine are
      related to the drug's enhancement of available dopamine at the synaptic cleft.
      The authors' goal was to determine whether this mechanism is the same in humans
      because the development of putative pharmacological agents for treatment of
      cocaine dependence depends on this knowledge. METHOD: Positron emission
      tomography with [11C]raclopride was used to examine the effects of the
      intravenous administration of 48 mg of cocaine (a typical "street" dose) on the
      occupancy of dopamine 2 receptors in the putamen of 11 self-identified
      intravenous drug abusers. RESULTS: All 11 subjects reported subjective
      stimulation and euphoria in response to cocaine administration. Radioligand
      occupancy at dopamine receptors was decreased significantly after cocaine
      administration, suggesting that higher dopamine concentrations were competing at
      the receptor site. CONCLUSIONS: These results support the concept of dopamine
      system involvement in human cocaine abuse.

PMID- 9286179
TI  - Are supplementary services provided during methadone maintenance really cost
      effective?
AB  - OBJECTIVE: Previous research has suggested that support services supplementing
      methadone maintenance programs vary in their cost-effectiveness. This study
      examined the cost-effectiveness of varying levels of supplementary support
      services to determine whether the relative cost-effectiveness of alternative
      levels of support is sustained over time. METHOD: A group of 100 methadone
      maintained opiate users were randomly assigned to three treatment groups
      receiving different levels of support services during a 24-week clinical trial.
      One group received methadone treatment with a minimum of counseling, the second
      received methadone plus more intensive counseling, and the third received
      methadone plus enhanced counseling, medical, and psychosocial services. The
      results at the end of the trial period have been published elsewhere. This
      article reports the results of an analysis at a 6-month follow-up. RESULTS: The
      follow-up analysis reaffirmed the preliminary findings that the methadone plus
      counseling level provided the most cost-effective implementation of the treatment
      program. At 12 months, the annual cost per abstinent client was $16,485, $9,804,
      and $11,818 for the low, intermediate, and high levels of support, respectively.
      Abstinence rates were highest, but modestly so, for the group receiving the high
      intensity, high-cost methadone with enhanced services intervention. CONCLUSIONS:
      This study suggests that large amounts of support to methadone-maintained clients
      are not cost-effective, but it also demonstrates that moderate amounts of support
      are better than minimal amounts. As funding for these programs is reduced, these
      findings suggest a floor below which supplementary support should not fall.

PMID- 9286180
TI  - Obstetric complications and age at onset in schizophrenia: an international
      collaborative meta-analysis of individual patient data.
AB  - OBJECTIVE: An excess of obstetric complications in the histories of schizophrenic
      patients is a well-replicated finding, but less consistent results have been
      found concerning the relationships between obstetric complications and family
      history of schizophrenia, age at onset of schizophrenia, and gender. Small sample
      size limited the power of previous studies that attempted to assess such
      relationships. The aim of this study was to use data on individual patients from
      all available studies to examine the links between a history of obstetric
      complications and family history of schizophrenia, age at onset, and gender.
      METHOD: Raw data from 854 schizophrenic patients concerning history of obstetric
      complications rated according to the Lewis and Murray scale were obtained from 11
      different research groups. Weighted average estimates were calculated with the
      use of regression techniques. RESULTS: A significant association was found
      between age at onset of schizophrenia and obstetric complications: the earlier
      the age at onset, the more likely the history of obstetric complications.
      Subjects with onset of schizophrenia before age 22 were 2.7 times more likely
      than those with onset at a later age to have had a history of abnormal
      presentation at birth and 10 times more likely to have had a history of
      complicated Cesarean birth. No association was found between obstetric
      complications and family history of schizophrenia or gender. CONCLUSIONS: The
      association between obstetric complications and early age at onset of
      schizophrenia indicates that the pathophysiology of early-onset schizophrenia
      involves neurodevelopmental impairment.

PMID- 9286181
TI  - Economic reforms and the acute inpatient care of patients with schizophrenia: the
      Chinese experience.
AB  - OBJECTIVE: This study compared insured and uninsured schizophrenic inpatients in
      China and examined changes in the acute inpatient care of schizophrenic patients
      during China's economic reform era. METHOD: Detailed chart reviews of 50 randomly
      selected inpatients discharged from a hospital in central China each year from
      1984 through 1993 identified 321 patients with schizophrenia. Demographic,
      insurance, treatment, and cost data of these patients were collected from the
      charts. RESULTS: With logistic regression models to control for confounding
      variables, the analyses showed that the 129 insured patients were significantly
      more likely than the 192 uninsured patients to be urban residents, to be older,
      to have had 7 or more years of schooling, and to have had more psychiatric
      hospitalizations; moreover, their index admissions were longer and were more
      likely to include use of traditional Chinese medications. The estimated 19% of
      schizophrenic individuals in the community with health insurance receive
      inpatient treatment 2.8 times more frequently than the 81% without insurance.
      Compared to admissions in 1984-1988, admissions in 1989-1993 were significantly
      shorter and involved longer periods of polypharmacy with multiple antipsychotic
      medications but included lower mean chlorpromazine-equivalent doses of
      medication. The relative cost of inpatient care for an acute episode of
      schizophrenia increased 3.5-fold over the 10-year period, from 11% of mean annual
      household income in 1984 to 37% in 1993. CONCLUSIONS: Changes in the incentive
      system for care providers and rapid increases in the cost of care during the
      economic reform era have resulted in increasingly restricted availability of
      services for the many schizophrenic patients without health insurance.

PMID- 9286182
TI  - Suicide and schizophrenia: a nationwide psychological autopsy study on age- and
      sex-specific clinical characteristics of 92 suicide victims with schizophrenia.
AB  - OBJECTIVE: The authors examined the clinical characteristics of suicide victims
      with schizophrenia in the general population of Finland. METHOD: As part of the
      nationwide National Suicide Prevention Project in Finland, all suicides over a 12
      month period of persons with DSM-III-R schizophrenia were investigated by using
      the psychological autopsy method. Clinical characteristics and their variation
      with age, sex, and illness duration were examined. RESULTS: Among all suicide
      victims, 7% (N = 92) were identified as having suffered schizophrenia. Suicides
      occurred throughout the course of schizophrenia. Both active illness (78%) and
      depressive symptoms (64%) were highly prevalent immediately before suicide, and a
      history of suicide attempts (71%) was also common. Women were more likely than
      men to have committed suicide during an acute exacerbation of the illness. Marked
      variation in depressive symptoms, alcoholism, and suicide methods was found among
      sexes and age groups. Alcoholism was most common among middle-aged men (45%),
      whereas middle-aged women had a high rate of depressive symptoms (88%). Younger
      male subjects most often used violent suicide methods. CONCLUSIONS: Suicide may
      occur at any point during the course of schizophrenia. The results indicate
      clinically important variation in depression, alcoholism, and suicide methods
      among suicide victims with schizophrenia. This suggestion of age- and sex
      specific risk factors for suicide in schizophrenia needs further investigation.

PMID- 9286183
TI  - Time to clozapine response in a standardized trial.
AB  - OBJECTIVE: The authors sought to determine the time to clozapine response in
      treatment-refractory patients with schizophrenia. METHOD: Antipsychotic response
      to a clozapine trial was examined in 50 treatment-refractory schizophrenic
      inpatients. Subjects were treated with clozapine for at least 12 months,
      regardless of response status, according to a standardized, increasing dose
      protocol. Behavioral changes were measured through monthly assessments with the
      Brief Psychiatric Rating Scale. RESULTS: Thirty-four subjects (68%) met clinical
      response criteria by the end of the trial. Response was achieved at a mean dose
      of 468 mg/day (SD = 168). The dose of 30 (88%) of the responding patients was 600
      mg/day or less. The mean time to response was 82 days (SD = 100, range = 10-401).
      It took an average of 60 days (SD = 87) for subjects to reach the dose at which
      clozapine response was achieved. Once this dose was reached, the average response
      time was 17 days (SD = 14, range = 2-56). All 34 subjects who responded met
      criteria within 8 weeks of a clozapine dose escalation. No late response was
      found in the remaining 16 subjects despite a mean follow-up period of 75 weeks
      (SD = 50). CONCLUSIONS: In this study, all patients who responded to clozapine
      did so within 8 weeks of a change in dose. Thus, there appears to be little
      clinical gain in prolonging exposure to clozapine beyond 8 weeks at any
      particular dose if no response is seen.

PMID- 9286184
TI  - Blind, controlled, long-term study of the comparative incidence of treatment
      emergent tardive dyskinesia with olanzapine or haloperidol.
AB  - OBJECTIVE: Tardive dyskinesia is a serious and common complication of neuroleptic
      treatment. Olanzapine is a novel antipsychotic agent exhibiting regional
      mesolimbic dopaminergic selectivity and a broad-based pharmacology encompassing
      serotonin, dopamine, muscarinic, and adrenergic receptor binding affinities. The
      authors' goal was to compare the incidence of tardive dyskinesia among patients
      receiving olanzapine and those receiving the conventional dopamine 2 antagonist
      haloperidol. METHOD: Data were analyzed from three actively controlled and blind
      long-term responder studies of subjects meeting DSM-III-R criteria for
      schizophrenia, schizophreniform disorder, or schizoaffective disorder treated
      with olanzapine (N = 707, up to 20 mg/day, 237 median days of exposure) or
      haloperidol (N = 197, up to 20 mg/day, 203 median days of exposure) who did not
      have evidence of tardive dyskinesia at baseline. All of the subjects had a
      chronic disease course (mean greater than 10 years), and there were no
      significant between-treatment group differences in demographic or disease
      characteristics. The Abnormal Involuntary Movement Scale and research diagnostic
      criteria for tardive dyskinesia were used to define the comparative incidence
      rates of long-term treatment-emergent tardive dyskinesia. RESULTS: The incidence
      of newly emergent tardive dyskinesia at any visit after baseline, at the final
      visit, and at the final two clinical assessments was statistically significantly
      lower among olanzapine-treated patients than among haloperidol-treated patients.
      CONCLUSIONS: These findings support an atypical extrapyramidal symptom profile
      and the potential of a significantly lower risk of tardive dyskinesia with
      olanzapine than with haloperidol among patients requiring maintenance
      antipsychotic treatment.

PMID- 9286185
TI  - Sertraline and desmethylsertraline in human breast milk and nursing infants.
AB  - OBJECTIVE: The purpose of this study was to determine the concentrations of
      sertraline and desmethylsertraline in both human breast milk and infant serum.
      METHOD: Breast milk samples from 12 women were collected at specific time
      intervals after oral doses of sertraline (25-200 mg once daily). For 11 mother
      infant pairs, maternal serum levels 24 hours after a dose and their infants'
      serum levels 2-4 hours after nursing were ascertained by high-performance liquid
      chromatography. RESULTS: Sertraline and desmethylsertraline were present in all
      breast milk samples, with a gradient from "fore" milk to "hind" milk. The highest
      concentrations of sertraline were observed in hind milk 7-10 hours after maternal
      dose. Increasing the maternal dose of sertraline resulted in increased breast
      milk concentrations of both sertraline and desmethylsertraline. Detectable
      concentrations of sertraline were found in three nursing infants and
      desmethylsertraline in six. No adverse effects of exposure were observed in any
      infant. CONCLUSIONS: Sertraline and desmethylsertraline were present in the
      breast milk of nursing women treated with sertraline. Concentrations were
      affected by aliquot of milk sampled, time after maternal dose, and maternal daily
      dose. The infants' serum concentrations detected were below the detection limit
      of most commercial laboratories. The presence of desmethylsertraline in six
      infants' samples underscores the importance of metabolite monitoring in
      determining infant exposure. Estimates of daily infant exposure can be determined
      after analysis of sertraline and desmethylsertraline concentrations from one full
      breast at maternal serum steady state. Future studies of breast milk and infant
      serum samples should address these issues.

PMID- 9286186
TI  - Placebo-controlled trial of fluoxetine and phenelzine for obsessive-compulsive
      disorder.
AB  - OBJECTIVE: It is now well documented that fluoxetine is a viable treatment option
      for patients with obsessive-compulsive disorder (OCD), and there is a small body
      of evidence indicating that monoamine oxidase inhibitors may be effective in at
      least a subset of patients. The authors conducted a 10-week placebo-controlled
      trial of these two agents in patients who met DSM-III-R criteria for OCD. METHOD:
      Sixty-four subjects were randomly assigned to receive placebo, phenelzine (60
      mg/day), or fluoxetine (80 mg/day). These doses were achieved by the end of week
      3 of the active phase of the study. Outcomes were assessed with standardized
      instruments to measure OCD, mood, and anxiety. RESULTS: Fifty-four patients
      completed the study. There was a significant difference among the three
      treatments on one OCD scale, with fluoxetine-treated patients improving
      significantly more than those in the placebo or phenelzine group. A subgroup of
      OCD patients with symmetry obsessions did respond to phenelzine. CONCLUSIONS:
      This study provides no evidence to support the use of phenelzine in OCD except
      possibly for those patients with symmetry or other atypical obsessions. There was
      also no support for the hypothesis that patients with high levels of anxiety
      would respond preferentially to phenelzine.

PMID- 9286187
TI  - Interaction between birth complications and early maternal rejection in
      predisposing individuals to adult violence: specificity to serious, early-onset
      violence.
AB  - OBJECTIVE: The authors previously reported that birth complications interact with
      early maternal rejection in predisposing individuals to violence at age 18 years.
      This study extended the follow-up period for violent offending from 18 years to
      34 years, thus increasing the sample of violent offenders threefold and allowing
      more detailed analyses on onset and type of violence, the form of maternal
      rejection, and the effect of maternal mental illness. METHOD: Complications in
      the births of 4,269 males in Denmark, maternal rejection of these individuals
      before the age of 1 year, and their histories of criminal offenses at age 34
      years were assessed. RESULTS: The biosocial interaction previously observed held
      for violent but not nonviolent crime, was specific to more serious forms of
      violence and not threats of violence, held for early-onset but not late-onset
      violence, and was not accounted for by psychiatric illness in the mothers. Being
      reared in a public care institution in the first year of life and the mother's
      attempt to abort the fetus were the key aspects of maternal rejection that
      interacted with birth complications in predisposing a subject to violence.
      CONCLUSIONS: These findings 1) indicate that the mechanisms underlying early
      onset, serious violence differ from those for less serious, late-onset violence,
      2) implicate very early factors in the development of violence, 3) highlight the
      potential importance of integrating psychosocial with biological factors in
      understanding and preventing violence, and 4) suggest that interventions to
      reduce birth complications and maternal rejection may help reduce violence.

PMID- 9286188
TI  - Utility of the initial therapeutic alliance in evaluating psychiatric patients'
      risk of violence.
AB  - OBJECTIVE: Evaluation of patients' potential for violence is an important
      component of care in psychiatric emergency and inpatient settings. Although
      situational variables are widely acknowledged to influence the risk of violence
      by psychiatric patients, most past research has been limited to patient
      attributes and has neglected the interpersonal context in which violence occurs.
      To the authors' knowledge, this is the first study to assess a new type of
      situational risk factor, the quality of the initial therapeutic alliance between
      the therapist and patient, as a predictor of the risk of violent behavior during
      short-term hospitalization. METHOD: The admitting physician's written initial
      evaluation for each of 328 patients hospitalized on a locked inpatient unit was
      reviewed by using a standardized alliance scale. The checklist measures the
      patient's level of active collaboration with the treatment process. Acute
      symptoms were rated at admission by physicians using the Brief Psychiatric Rating
      Scale. Nurses rated aggressive behavior in the hospital with the Overt Aggression
      Scale. RESULTS: Patients who had a poorer therapeutic alliance at the time of
      admission were significantly more likely to display violent behavior during
      hospitalization. Logistic regression analysis showed that the quality of the
      initial therapeutic alliance remained a strong predictor of violence even when
      other clinical and demographic correlates of violence were considered
      concurrently. CONCLUSIONS: The results suggest a new class of situational,
      interactional variable--reflected in the quality of the therapeutic relationship-
      that may be useful in evaluating patients' potential for violence. Implications
      for risk management are discussed.

PMID- 9286189
TI  - Decreased motor inhibition in Tourette's disorder: evidence from transcranial
      magnetic stimulation.
AB  - OBJECTIVE: Fluctuating motor and vocal tics are the diagnostic feature of
      Tourette's disorder. The pathophysiology of tics is still unclear. One major
      hypothesis is a deficient inhibitory control through the cortical-striatal
      thalamic-cortical motor loop. The authors tested this hypothesis by investigating
      motor cortex excitability through use of the technique of transcranial magnetic
      stimulation. METHOD: Twenty patients with Tourette's disorder and a comparison
      group of 21 healthy subjects were studied. Focal transcranial magnetic
      stimulation was applied to the left motor cortex, and surface electromyography
      (EMG) was recorded from the right abductor digiti minimi muscle. As measures of
      motor cortex excitability, motor threshold, cortical silent period, and
      intracortical inhibition and facilitation were studied. The peripheral silent
      period and the maximum M wave after supramaximal electrical stimulation of the
      ulnar nerve at the wrist were also determined. RESULTS: Motor threshold and
      peripheral motor excitability were normal in the Tourette's disorder group, but
      the cortical silent period was shortened and the intracortical inhibition
      reduced. A subgroup analysis of the patients with Tourette's disorder revealed
      that these abnormalities were seen mainly when tics were present in the EMG
      target muscle or in patients without neuroleptic treatment. Age, sex, attention
      deficit hyperactivity disorder, obsessive-compulsive disorder, and sensory urges
      had no significant effect on motor excitability. CONCLUSIONS: Findings are
      consistent with the hypothesis that tics in Tourette's disorder originate either
      from a primarily subcortical disorder affecting the motor cortex through
      disinhibited afferent signals or from impaired inhibition directly at the level
      of the motor cortex or both.

PMID- 9286190
TI  - Refusal of ECT by a patient with recurrent depression, psychosis, and catatonia.

PMID- 9286191
TI  - Addition of desipramine to serotonin reuptake inhibitors in treatment-resistant
      obsessive-compulsive disorder.
AB  - OBJECTIVE: The purpose of this study was to determine whether combined treatment
      with a selective serotonin reuptake inhibitor (SSRI) and a norepinephrine
      reuptake inhibitor, desipramine, effectively reduces obsessive-compulsive
      symptoms in patients who do not respond to SSRIs. METHOD: In a double-blind
      study, desipramine or placebo was added for 6 or 10 weeks to the treatment of 30
      patients with obsessive-compulsive disorder whose symptoms were refractory to
      SSRI treatment (fluvoxamine, fluoxetine, or sertraline) alone. RESULTS: There
      were no significant differences between the adjunctive desipramine and placebo
      groups in obsessive-compulsive or depressive symptoms. CONCLUSIONS: These data
      suggest that clomipramine's possibly superior efficacy in the treatment of
      obsessive-compulsive symptoms may not stem from its capacity to inhibit reuptake
      of norepinephrine.

PMID- 9286192
TI  - PET study of greater visual activation in schizophrenia.
AB  - OBJECTIVE: The authors tested the hypothesis that photic visual stimuli cause a
      greater blood flow activation response in subjects with schizophrenia than in
      normal subjects. METHOD: Eleven medicated patients with schizophrenia and 10
      normal subjects were studied with [15O]H2O positron emission tomography to
      measure perfusion during photic stimulation at four different rates. RESULTS: The
      activation at three out of four rates of visual stimulation was greater for the
      patients with schizophrenia than it was for the normal subjects. CONCLUSIONS:
      Further investigation into the mechanisms of activation during sensory
      stimulation in schizophrenia is warranted.

PMID- 9286193
TI  - Comparison of patients with early-, typical-, and late-onset affective psychosis.
AB  - OBJECTIVE: The authors compared the clinical characteristics and family history
      of patients with early-onset (before age 18), typical-onset (at 20-25 years), and
      late-onset (after age 35) affective psychosis at the time of first
      hospitalization. METHOD: Diagnostic, symptom, and family history information was
      obtained from 88 consecutively hospitalized patients. RESULTS: Major depression
      was more common in the late-onset group, and a family history of affective and
      substance abuse disorders was more common among the early-onset patients.
      Affective symptoms differed significantly among groups; specifically, early-onset
      patients had more energy, minimal sleep disruption, and greater suicidality,
      while typical-onset patients had more severe abnormal thought content.
      CONCLUSIONS: Among patients with affective psychosis, there may be heterogeneity
      of symptoms and family history associated with age at first hospitalization.

PMID- 9286194
TI  - Assertive community treatment and medication compliance in the homeless mentally
      ill.
AB  - OBJECTIVE: This study describes medication compliance rates among a group of
      homeless mentally ill subjects who received assertive community treatment.
      METHOD: The medication compliance of 77 homeless persons who had been referred to
      an assertive community treatment program was prospectively evaluated at baseline
      and quarterly for 1 year. RESULTS: A minority of the cohort (29%) was compliant
      at entry into the assertive community treatment program. Compliance significantly
      increased after 3 months (57%) and remained high through the year. Medication
      compliance was associated with fewer psychiatric symptoms but not with better
      housing placements or fewer days in the hospital. CONCLUSIONS: Medication
      compliance rates among a cohort of homeless persons with severe mental illness
      were markedly higher after they entered a program of assertive community
      treatment.

PMID- 9286195
TI  - Controlled study of psychiatric comorbidity in psychiatrically hospitalized young
      adults with substance use disorders.
AB  - OBJECTIVE: The purpose of this study was to examine DSM-III-R axis I and axis II
      comorbidity in psychiatrically hospitalized young adults with substance use
      disorders. METHOD: Structured diagnostic interviews were given to 117 consecutive
      inpatients. Seventy patients with substance use disorders and 47 patients without
      substance use disorders were compared. RESULTS: High rates of co-occurrence of
      axis I disorders were observed, but no disorder coexisted in the group with
      substance use disorders at a significantly higher rate than in the group without
      substance use disorders. Among axis II disorders, borderline personality disorder
      was diagnosed significantly more frequently in the group with substance use
      disorders. CONCLUSIONS: Significant additional diagnostic co-occurrence, defined
      as comorbidity, was observed only between borderline personality disorder and
      substance use disorders. The use of a relevant psychiatric comparison group
      allows for finer distinctions between covariation based on shared severity and
      comorbidity possibly based on shared pathophysiology.

PMID- 9286196
TI  - Propranolol treatment of olanzapine-induced akathisia.

PMID- 9286197
TI  - Canine variant of factitious disorder by proxy.

PMID- 9286198
TI  - Lamotrigine for treatment-refractory bipolar disorder.

PMID- 9286199
TI  - Fluvoxamine-induced theophylline toxicity.

PMID- 9286200
TI  - Nephrotic syndrome associated with lithium therapy.

PMID- 9286201
TI  - Photic maculopathy in a patient receiving bright light therapy.

PMID- 9286202
TI  - PTSD after a peacekeeping mission.

PMID- 9286203
TI  - Hair pulling in a patient with Sydenham's chorea.

PMID- 9286204
TI  - Montgomery-Asberg severity gradations.

PMID- 9286205
TI  - Tarasoff ruling and reporting to the authorities.

PMID- 9286206
TI  - Borderline mnemonic.

PMID- 9286207
TI  - Chronic fatigue.

PMID- 9286208
TI  - Lewy bodies.

PMID- 9286209
TI  - Lewy bodies.

PMID- 9286210
TI  - Advancing age, declining ADHD.

PMID- 9286212
TI  - Psychiatry's future.

PMID- 9286213
TI  - Psychiatry's future.

PMID- 9286214
TI  - Psychiatry's future.

PMID- 9286215
TI  - Physician-assisted suicide in Oregon.

PMID- 9286216
TI  - Physician-assisted suicide in Oregon.

PMID- 9286217
TI  - Biopsychosocial model.

PMID- 9286218
TI  - Abandonment and intrusion fears in borderline personality disorder.

PMID- 9286220
TI  - Cryptosporidiosis and inflammatory bowel disease. Experience from the Milwaukee
      outbreak.
AB  - The 1993 Milwaukee Cryptosporidium outbreak posed several questions regarding
      appropriate management and prognosis of inflammatory bowel disease patients
      acutely infected with this organism. We prospectively identified and monitored 12
      patients with stable ulcerative colitis or Crohn's disease who suffered abrupt
      clinical decompensation during the outbreak. All recovered to baseline at < or =
      60 days. In patients receiving immunosuppressive therapy, mean duration of
      symptoms was no longer than in patients without it. Antibiotics did not clearly
      reduce duration of illness. Two additional patients without a history of
      intestinal disease presented with ileitis and colitis, respectively, initially
      suggesting Crohn's disease. Both recovered completely without specific therapy.
      We conclude that cryptosporidiosis may present as an acute relapse of
      inflammatory bowel disease and responds to standard therapy; antibiotics confer
      no obvious benefit. Immunosuppressive therapy does not predispose to chronic or
      severe illness in these patients. Cryptosporidiosis may present with acute
      findings initially mimicking Crohn's disease.

PMID- 9286219
TI  - Colonic sulfide in pathogenesis and treatment of ulcerative colitis.
AB  - A role for colonic sulfide in the pathogenesis and treatment of ulcerative
      colitis (UC) has emerged based on biochemical, microbiological, nutritional,
      toxicological, epidemiological, and therapeutic evidence. Metabolism of isolated
      colonic epithelial cells has indicated that the bacterial short-chain fatty acid
      n-butyrate maintains the epithelial barrier and that sulfides can inhibit
      oxidation of n-butyrate analogous to that observed in active UC. Sulfur for
      fermentation in the colon is essential for n-butyrate formation and
      sulfidogenesis aids disposal of colonic hydrogen produced by bacteria. The
      numbers of sulfate-reducing bacteria and sulfidogenesis is greater in UC than
      control cases. Sulfide is mainly detoxified by methylation in colonic epithelial
      cells and circulating red blood cells. The enzyme activity of sulfide methylation
      is higher in red blood cells of UC patients than control cases. Patients with UC
      ingest more protein and thereby sulfur amino acids than control subjects.
      Removing foods rich in sulfur amino acids (milk, eggs, cheese) has proven
      therapeutic benefits in UC. 5-Amino salicylic acid reduces fermentative
      production of hydrogen sulfide by colonic bacteria, and aminoglycosides, which
      inhibit sulfate-reducing bacteria, are of therapeutic benefit in active UC.
      Methyl-donating agents are a category of drugs of potential therapeutic use in
      UC. A correlation between sulfide production and mucosal immune responses in UC
      needs to be undertaken. Control of sulfidogenesis and sulfide detoxification may
      be important in the disease process of UC, although whether their roles is in an
      initiating or promoting capacity has yet to be determined.

PMID- 9286221
TI  - Improvement in specificity of [14C]d-xylose breath test for bacterial overgrowth.
AB  - The aim of the study was to determine whether the specificity of the [14C]d
      xylose breath test could be improved, by excluding false-positive tests due to
      premature colonic metabolism of the [14C]d-xylose caused by rapid colonic
      transit. Forty-seven patients with suspected small bowel bacterial overgrowth
      were investigated by (1) aspiration and culture of duodenal fluid and (2) a
      [14C]d-xylose breath test. Those with either a positive duodenal culture or
      breath test had a repeat [14C]d-xylose breath test given with one of three
      transit markers (barium, Gastrografin or 99mTc-labeled tin colloid) to determine
      if the site of metabolism was in the small bowel or colon. Fourteen patients had
      positive duodenal cultures, four of whom had a negative [14C]d-xylose breath
      test, 15 patients had a positive [14C]d-xylose breath test, three of which were
      due to colonic metabolism of the xylose. Where transit markers were used, 14C was
      detectable in the breath and serum before barium had entered the small bowel,
      thus the barium did not comigrate with the xylose. Gastrografin accelerated small
      bowel transit, leading to malabsorption of the xylose in the small intestine and
      subsequent colonic metabolism of the xylose. 99mTc-labeled tin colloid had no
      obvious disadvantages and appeared to be the marker of choice. The use of a
      transit marker increased the specificity of the [14C]d-xylose breath test from
      85% to 94%. The specificity of the [14C]d-xylose breath test for the detection of
      small bowel bacterial overgrowth is improved to greater than 90% by the use of an
      appropriate transit marker.

PMID- 9286222
TI  - Antinuclear autoantibodies in patients with inflammatory bowel disease. High
      prevalence in first-degree relatives.
AB  - Crohn's disease and ulcerative colitis show a familial aggregation. The role of
      antinuclear autoantibodies, which occur in both diseases, remains to be defined.
      In 76 patients with Crohn's disease, 61 patients with ulcerative colitis, 105
      first-degree relatives of patients with Crohn's disease, 101 first-degree
      relatives of patients with ulcerative colitis, and 40 healthy unrelated controls
      antinuclear autoantibodies were detected by indirect immunofluorescence.
      Existence of autoantibodies was correlated with clinical features. Eighteen
      percent of patients with Crohn's disease (14/76), 43% of patients with ulcerative
      colitis (26/61), 13% of relatives of patients with Crohn's disease (14/105), 24%
      of relatives of ulcerative colitis patients (24/101), and 2% of the healthy
      controls (1/40) were positive for antinuclear autoantibodies. The difference
      between controls and patients and the first-degree relatives of patients with
      ulcerative colitis, respectively, was statistically significant (P < or =
      0.0144). In ulcerative colitis, the existence of antinuclear autoantibodies was
      negatively correlated with immunosuppressive therapy or extraintestinal
      manifestations (P = 0.0004 and 0.0273, respectively). Antinuclear autoantibodies
      may represent a factor disposing to the development of ulcerative colitis.

PMID- 9286223
TI  - Effect of L-lactic acid, short-chain fatty acids, and pH in cecal infusate on
      morphometric and cell kinetic parameters of rat cecum.
AB  - We studied the influences of cecal infusion of NaCl, short-chain fatty acids
      (SCFA), and L-lactic acid at pH 5.0 or 7.0 for seven days on morphometric and
      cell kinetic parameters of the rat cecum. SCFA increased relative weight of the
      mucosa and submucosa, crypt size, and mitotic index in the cecum. L-Lactic acid
      stimulated mitosis only at pH 5.0. Crypt size correlated positively to epithelial
      proliferative activity only when NaCl or L-lactic acid was infused. SCFA should
      have changed the balance between production and loss of the cecal epithelial
      cells. The infusate pH by itself had no effect, but modified the effects of SCFA
      and L-lactic acid in different ways. Crypt size correlated positively to the
      logarithm of daily proton load of infusates. The above results indicate that
      epithelial cell proliferation in the cecum is influenced by both SCFA and L
      lactic acid, although differently, and by proton load.

PMID- 9286224
TI  - Lactobacillus flora in short bowel syndrome.

PMID- 9286225
TI  - Effect of viscous fiber (guar) on postprandial motor activity in human small
      bowel.
AB  - Both caloric value and chemical composition of a meal have been shown to regulate
      postprandial small bowel motility in dog. In the same species, duration of and
      contractile activity within the postprandial period also depends on mean
      viscosity. It is unknown, however, whether meal viscosity and fiber content also
      regulate small bowel motor activity in man. In human volunteers, we therefore
      studied the effect of guar gum on small bowel motor response to liquid and solid
      meals. Twenty-six prolonged ambulatory small bowel manometry studies were
      performed in 12 volunteers. A total of 620 hr of recording were analyzed visually
      for phase III of the MMC and a validated computer program calculated the
      incidence and amplitude of contractions after ingestion of water (300 ml), a pure
      glucose drink (300 ml/330 kcal) or a solid meal (530 kcal) with and without 5 g
      of guar gum. Addition of 5 g of guar gum did not significantly delay reappearance
      of phase III after ingestion of water (59 +/- 11 vs 106 +/- 21 min; P = 0.09).
      However, guar gum significantly prolonged duration of postprandial motility
      pattern both after the glucose drink (123 +/- 19 vs 199 +/- 24 min; P < 0.05) and
      after the solid meal (310 +/- 92 vs 419 +/- 22 min; P = 0.005). Contractile
      activity during these periods was not affected by guar gum. This was true for
      mean incidence of contractions after water (1.9 +/- 0.3 vs 1.8 +/- 0.5 min-1),
      after the glucose drink (1.6 +/- 0.4 vs. 1.7 +/- 0.3 min-1) and after the solid
      meal (2.4 +/- 0.4 vs 2.6 +/- 0.4 min-1). Likewise, mean amplitude of contractions
      was not affected by guar gum after water (22.8 +/- 1.4 vs 20.9 +/- 1.9 mm Hg),
      after the glucose drink (20.5 +/- 1.4 vs 21.3 +/- 1.2), and after the solid meal
      (20.3 +/- 1.5 vs 21.5 +/- 1.6 mm Hg). Thus a guar gum-induced increase in chyme
      viscosity markedly prolonged duration of postprandial motor activity in the human
      small bowel. Contractile activity within the postprandial period, however, was
      not affected. We suggest that the postprandial motility pattern persisted longer
      after the more viscous meals, because gastric emptying and intestinal transit
      were delayed by guar gum. We conclude that it is essential to define meal
      viscosity and fiber contents when studying postprandial small bowel motility.

PMID- 9286227
TI  - Effect of ethanol on postprandial duodenojejunal motility in humans.
AB  - The effect of ethanol on postprandial small bowel motility was investigated in
      eight healthy volunteers using perfusion of nutrient solutions (17% proteins, 59%
      carbohydrates, 24% lipids) into the descending duodenum (5 ml/min for 120 min).
      An ethanol-containing solution (4% w/v, 4.06 kcal/min, 1190 mosmol/kg) was
      compared with the corresponding ethanol-free solution (2.64 kcal/min, 160
      mosmol/kg) and another ethanol-free hyperosmolar solution adapted in caloric load
      and osmolality (4.06 kcal/min, 1160 mosmol/kg). Motility was recorded with a data
      logger and six pressure transducers at 3-cm intervals around the duodenojejunal
      flexure. Clustered contractions (27 +/- 4/hr) migrating aborally through the
      whole recording segment were the predominant motor pattern with ethanol compared
      with the ethanol-free (10 +/- 2/hr; P < 0.01) and the ethanol-free hyperosmolar
      solution (6 +/- 3/hr; P < 0.001). Other motility parameters with ethanol were not
      different from the ethanol-free solution, whereas the ethanol-free hyperosmolar
      solution showed a much less intense motor response. We conclude that ethanol does
      modify human postprandial duodenojejunal motility by inducing propagative motor
      patterns.

PMID- 9286226
TI  - Ambulatory small intestinal manometry. Detailed comparison of duodenal and
      jejunal motor activity in healthy man.
AB  - The aim of this study were to provide a detailed comparison of duodenal and
      jejunal motor activity in healthy individuals by utilizing prolonged ambulatory
      manometry in combination with computer-aided analysis. Intraluminal pressure
      profiles were studied in the duodenum and jejunum of 18 healthy volunteers over
      24 hr. The subjects ingested two meals, both of 800 kcal and of equal chemical
      composition, at two different times of the day. Over the whole interdigestive
      period, phase III motor activity started more frequently distal than proximal to
      the ligament of Treitz. However, an increasing time of fasting was linearly
      related to an increasing number of phase IIIs originating proximal to the
      ligament of Treitz (r = 0.95). Both meals induced a postprandial motor pattern of
      similar duration and contractile activity. As compared to the jejunum, individual
      duodenal contractions during the postprandial period and during phase II had a
      higher duration and amplitude. Propagated clustered contractions occurred more
      frequently in the duodenum than in the jejunum, both in the interdigestive and
      digestive state. Jejunal clusters comprised a higher number of individual
      contractions of lower amplitude and duration. In healthy man duodenal and jejunal
      motor activity are different, both in the digestive and interdigestive state. The
      differences include the number of activity fronts traversing these segments of
      the gut, the number and organization of propagated clustered contractions, and
      subtle changes in the amplitude, duration, and coordinated propagation of
      individual contractions. These changes presumably reflect a regulatory capability
      of the small intestine to modulate the rate of transit of intraluminal content
      through different segments of the gut.

PMID- 9286228
TI  - Effects of octreotide on manometric variables in patients with neuropathic
      abnormalities of the small bowel.
AB  - At present, there are few therapeutic options in patients with chronic intestinal
      dysmotilities. Octreotide, a long-acting somatostatin analog, has recently been
      shown to be a potentially useful drug in this setting, being able to start
      activity fronts (AF) in the small bowel in both healthy subjects and patients
      with intestinal motor disorders. We studied the effects of octreotide on
      manometric variables in 10 patients with chronic upper gastrointestinal symptoms
      and an intrinsic neuropathic disorder of the small intestine. Gastrointestinal
      manometry was carried out for 6 hr during fasting and 2 hr after a standard 605
      kcal mixed meal. Thereafter octreotide, 50 micrograms subcutaneously was
      administered and the recording session continued for a further hour. Analysis of
      the tracings during fasting showed that 44% of the AF were abnormal; octreotide
      significantly increased the hourly number of AF (2 +/- 0.26 vs 0.67 +/- 0.14, P <
      0.0001) and their duration (8.33 +/- 1.3 vs 6.12 +/- 0.34 min, P < 0.05) with
      respect to the baseline (fasting) period, and the propagation velocity also
      significantly slowed (3.4 +/- 0.4 vs 11 +/- 0.6 cm/min, P < 0.05). After the
      drug, 80% of patients displayed two AF and 10% more than two AF; the first AF
      after octreotide was always abnormally propagated. An almost complete inhibition
      of small bowel postprandial contractile activity was observed in 80% of patients,
      and the remaining 20% showed decreases. In three subjects, octreotide injection
      evoked the appearance of pylorospasm. From these results we conclude that
      octreotide could be of some benefit in patients with neuropathic disorders of the
      small bowel, although it remains to be established whether it is most useful in
      patients with more severe conditions, characterized by the complete absence of
      AF. The appearance of pylorospasm may contribute to the delayed gastric emptying
      observed after the drug is administered.

PMID- 9286229
TI  - Endotoxin actions on myoelectric activity, transit, and neuropeptides in the gut.
      Role of nitric oxide.
AB  - The lipopolysaccharide (endotoxin) of gram-negative bacteria has systemic effects
      in animals and man. Our aim was to investigate the effects of E. coli
      lipopolysaccharide on motility and transit through the small intestine in rats
      and to analyze plasma and tissue concentrations of intestinal neuropeptides. When
      lipopolysaccharide (20-160 micrograms/kg) was administered intravenously, the
      migrating myoelectric complex was replaced by spike bursts accompanied by rapid
      transit. Tissue concentrations of substance P and neurokinin A decreased, while
      plasma levels of calcitonin gene-related peptide increased N omega-Nitro-L
      arginine, N omega-L-arginine methyl ester, dexamethasone, or indomethacin
      prevented these changes in myoelectric activity and tissue contents of
      neuropeptides. All of these compounds, except indomethacin, prevented the
      increased rate of transit. Thus, lipopolysaccharide changes motility through the
      nitric oxide and arachidonic pathways, resulting in rapid transit through the
      gut.

PMID- 9286230
TI  - Serum antibodies against Helicobacter pylori proteins VacA and CagA are
      associated with increased risk for gastric adenocarcinoma.
AB  - Infection with Helicobacter pylori is associated with the development of gastric
      cancer. To study whether the infection with H. pylori strains expressing the
      vacuolating cytotoxin (VacA) and/or the cytotoxin-associated protein (CagA) is
      associated with an increased risk of developing gastric adenocarcinoma, sera of
      90 patients with gastric cancer and 90 matched controls with cardiovascular
      diseases were investigated for the presence of antibodies to VacA and CagA by
      immunoblot. Although no significant difference in the overall H. pylori
      seropositivity was found between cancer patients and controls, antibodies against
      VacA or CagA were significantly more frequent in cancer patients than in control
      subjects. Seventy-five (97.4%) of 77 H. pylori-positive patients in the cancer
      group, but only 60 (84.5%) of 71 H pylori-positive control patients had
      antibodies against either VacA or CagA (chi 2 = 6.63; relative risk, 2.00; 95%
      confidence interval, 1.18-3.39; P = 0.01). The presence of antibodies against
      VacA or CagA alone was also associated with an increased cancer risk (92.2% vs
      80.3%; chi 2 = 5.30; relative risk, 1.74; 95% confidence interval, 1.08-2.78; P =
      0.021, for VacA; and 87.0% vs 74.6%; chi 2 = 4.90; relative risk, 1.61; 95%
      confidence interval, 1.06-2.45; P = 0.037, for CagA). The relative risk for
      gastric cancer was mainly elevated in patients under 65 years, but not in
      patients at or over 65 years. There is evidence that infection with VacA- or CagA
      producing H. pylori strains increases the risk of developing gastric cancer,
      especially in younger patients.

PMID- 9286231
TI  - A prospective study of prognostic value of type IV collagenase activity in
      colorectal cancer tissue.
AB  - The purpose of this prospective study was to evaluate the prognostic value of the
      type IV collagenase (IVase) activity in colorectal cancer tissue on disease-free
      and overall survival in 31 colorectal cancer patients. The clinicopathologic
      factors studied for prognostic value were age, tumor location, tumor
      differentiation, preoperative serum levels of carcinoembryonic antigen, Dukes'
      stage, and IVase activity in colorectal cancer tissue. IVase activities in
      colorectal cancer tissue were significantly higher in the group of patients with
      recurrences than in the group without recurrences (P = 0.019). Patients with high
      IVase activity in colorectal cancer tissue had a significantly shorter disease
      free survival (P = 0.0016) and overall survival (P = 0.022) time than those with
      low IVase activity. Univariate and multivariate analysis showed that significant
      prognostic factors for disease-free survival were Dukes' stage (P = 0.029, P =
      0.046, respectively) and IVase activity status (P = 0.0016, P = 0.0026,
      respectively). With respect to overall survival, only IVase activity status
      provided significant predictive value in multivariate analysis (P = 0.041). This
      prospective study suggests that IVase activity is a valuable prognostic factor in
      colorectal cancer patients.

PMID- 9286232
TI  - Medical problems occurring after orthotopic liver transplantation.
AB  - Liver transplantation is complicated by specific medical problems. Diabetes
      mellitus occurs in 4-20% of patients undergoing liver transplantation. Patients
      with primary sclerosing cholangitis and ulcerative colitis experience up to a 13%
      incidence of colon cancer after transplantation. Lymphomas occur in 1-3% of
      patients after transplantation and account for 57% of malignancies occurring in
      adult patients. Atraumatic bone fractures occur in 22-38% of patients and
      neurological complications, including seizures, headache, and neuropathy occur in
      19-47% of patients following liver transplantation. Patients undergoing liver
      transplantation may experience recurrence of their primary liver disease:
      hepatitis B, hepatitis C, primary biliary cirrhosis, autoimmune hepatitis, or
      primary sclerosing cholangitis. In patients not receiving immunoprophylaxis after
      transplantation for chronic hepatitis B, recurrent hepatitis B is seen in up to
      90% of patients. This can be markedly reduced with hyperimmune globulin
      immunoprophylaxis. Recurrent hepatitis C is seen in the majority of patients;
      current treatment modalities are inadequate. Recurrence of primary biliary
      cirrhosis or primary sclerosing cholangitis in the allograft is infrequent.
      Autoimmune hepatitis may recur in up to 26% of patients following liver
      transplantation. Primary disease recurrence in the allograft and preventive
      strategies are discussed.

PMID- 9286233
TI  - Lack of hepatocyte growth factor receptor (c-met) gene expression in fulminant
      hepatic failure livers before transplantation.
AB  - To gain insight into liver regeneration mechanisms in fulminant hepatic failure,
      we compared gene expression of hepatocyte growth factor, its receptor c-met, c
      myc, and albumin in human normal (4 cases) and fulminant (14 cases) livers by
      reverse transcription-polymerase chain reaction. In normal livers, hepatocyte
      growth factor gene was not expressed, whereas c-met, c-myc and albumin genes were
      always expressed. In fulminant hepatic failure, hepatocyte growth factor gene was
      expressed in 1 of 14 cases, c-met in none of 14 cases, c-myc in 10 of 14 cases,
      and albumin in 3 of 14 cases. By immunofluorescence, c-met protein was revealed
      in normal but not in fulminant hepatic failure liver tissue. Liver tissue is
      unlikely to account for high hepatocyte growth factor plasma levels typical for
      fulminant hepatic failure. Lack of its receptor (c-met) expression may explain a
      poor response of fulminant hepatic failure livers to exogenous hepatocyte growth
      factor that normally promotes liver growth and regeneration.

PMID- 9286234
TI  - Treatment of chronic hepatitis C with amantadine.
AB  - Treatment of chronic hepatitis C infection with interferon has been
      disappointing, with less than one third of patients achieving a sustained
      response and most experiencing significant side effects. For these reasons, an
      open-labeled prospective pilot study was conducted to test the safety and
      efficacy of the antiviral drug, amantadine, in patients with chronic hepatitis C
      infection who had previously failed therapy with interferon-alpha 2b. Twenty-two
      patients with chronic hepatitis C were enrolled into the study and treated with
      amantadine 100 mg orally twice daily for six months. Control groups included the
      same cohort followed off therapy for 29-36 months or during therapy with
      interferon. Serum alanine aminotransferase (ALT) values decreased in 64% (P =
      0.01) of patients with amantadine therapy compared to intervals without therapy
      or to interferon therapy. Twenty-seven percent of patients treated with
      amantadine had normalization of ALT values and loss of HCV RNA after six months
      while 18% achieved a sustained response with loss of HCV RNA by PCR six months
      after discontinuation of amantadine. Therapy with amantadine improved both
      biochemical and virological markers in patients with hepatitis C who had
      previously not responded to treatment with interferon.

PMID- 9286235
TI  - Antinuclear antibodies and patterns of nuclear immunofluorescence in type 1
      autoimmune hepatitis.
AB  - To determine the significance of antinuclear antibodies and their patterns of
      indirect immunofluorescence in type 1 autoimmune hepatitis, sera from 99 patients
      were evaluated. Patients with antinuclear antibodies had a lower frequency of
      liver transplantation (6% vs 22%, P = 0.04) than seronegative patients. They were
      also more commonly HLA-DR4-positive than seronegative patients (56% vs 30%, P =
      0.05) and normal subjects (56% vs 30%, P = 0.004). The 42 patients with
      antinuclear antibodies and a diffuse pattern of indirect immunofluorescence had
      higher serum titers of ANA (serum titers > or = 1:500, 71% vs 14%, P < 0.0001)
      and SMA (serum titers > or = 1:500, 69% vs 27%, P = 0.003) than the 22 patients
      with antinuclear antibodies and a speckled pattern. These patients, however, were
      otherwise not distinguished by clinical features and treatment response. Patients
      with a speckled pattern had A1-B8-DR3 more frequently than patients with a
      diffuse pattern (65% vs 23%, P = 0.005) and normal subjects (65% vs 13%, P <
      0.0001), but they had no other salient features. We conclude that patients with
      antinuclear antibodies have a better long-term prognosis than seronegative
      patients, and they have HLA-DR4 more commonly. The patterns of indirect
      immunofluorescence associated with ANA positivity have no practical clinical
      implications.

PMID- 9286236
TI  - Anemia worsens hyperdynamic circulation of patients with cirrhosis and portal
      hypertension.
AB  - This retrospective cohort study was aimed at investigating the effects of anemia
      on the hemodynamic disturbances associated with portal hypertension. In all, 202
      consecutive nontreated portal-hypertensive patients referred for evaluation to
      our Hepatic Hemodynamic Laboratory were included. Compared to the nonanemic
      patients, anemic cirrhotic patients had an increased cardiac output (7.9 +/- 1.9
      vs 7.1 +/- 2 liters/min, P < 0.01), and a decreased mean arterial blood pressure
      (82 +/- 11 vs 94 +/- 13 mm Hg, P < 0.0001) and systemic vascular resistance (838
      +/- 235 vs 1102 +/- 356 dyn/sec/cm5, P < 0.0001). Similar results were obtained
      when Child A or Child B-C patients were analyzed separately. Multivariate
      logistic regression disclosed that hemoglobin concentration, in addition to age,
      sex azygos blood flow, and albumin concentration, was an independent factor
      influencing the degree of systemic vasodilation in cirrhotic portal-hypertensive
      patients. This study discloses that anemia worsens the hyperdynamic circulation
      associated with portal hypertension. Since hemoglobin concentration may change
      with time, this parameter should be taken into account when evaluating
      hemodynamics in portal-hypertensive patients.

PMID- 9286238
TI  - Reinfusion of concentrated ascitic fluid versus total paracentesis. A randomized
      prospective trial.
AB  - We compared the efficacy and safety of apheresis and reinfusion of concentrated
      ascites (ARCA) versus total paracentesis plus intravenous albumin (PARA) in a
      prospective trial on cirrhotic patients with tense ascites. Twenty-four patients
      were randomized to either ARCA (N = 12) or PARA (N = 12), and followed for two
      years. Sex, age, Child's class, and renal and liver function were similar in the
      two groups. The times the procedures were 2.7 +/- 1.0 (ARCA) vs 2.2 +/- 1.1
      (PARA) hr, with removal of 8.8 +/- 3.5 (ARCA) and 6.9 +/- 3.4 (PARA) liters of
      ascites and intravenous infusion of 59.8 +/- 35.2 (ARCA) and 42.5 +/- 20.5 (PARA)
      g of albumin. Both procedures were safe. Biochemical signs of coagulative
      disturbances having no clinical relevance were observed after ARCA, with an
      increase in prothrombin time (P = 0.005) and serum FSP (P = 0.02). No significant
      changes in renal function, serum albumin, or plasma and urinary electrocytes were
      shown. Plasma renin activity increased after PARA (P = 0.02) and plasma atrial
      natriuretic factor increased after ARCA (P = 0.008), although no differences were
      observed in diuresis in the immediate follow-up. During the long-term follow-up,
      patient survival and recurrence of tense ascites were the same in both groups. We
      conclude that apheresis and reinfusion of concentrated ascites are as safe and
      effective as total paracentesis with albumin infusion for the treatment of tense
      ascites in cirrhotic patients.

PMID- 9286239
TI  - Hepatotoxic agent thioacetamide induces biochemical and histological alterations
      in rat small intestine.
AB  - We have assessed the effect of the oral ingestion of thioacetamide on small
      intestine structure and function. Thioacetamide-treated rats showed diminished
      mucosa weight; protein, DNA, and RNA content; and leucine aminopeptidase activity
      as compared to controls in both jejunum and ileum. In the jejunum, there was a
      reduction in the activities of alkaline phosphatase, ATPase, glucose-6
      phosphatase, and myeloperoxidase, whereas in the ileum, maltase, lactase, and
      gamma-glutamyltranspeptidase were reduced. In both jejunum and ileum we found
      enlarged intercellular spaces, dark epithelial enterocytes, and lymphocyte
      infiltration. Enterocytes showed lobulated nuclei, deranged mitochondria with
      loss of their cristae, dilated rough endoplasmic reticulum containing dense
      material, and vesiculation of the smooth endoplasmic reticulum and the Golgi
      apparatus. Smooth muscle cells of the intestine exhibited ultrastructural
      alterations. These findings indicate that chronic oral intake of thioacetamide
      mimics not only hepatic alterations but also small intestine alterations normally
      associated with human cirrhosis.

PMID- 9286237
TI  - Serum HCV-RNA and liver histologic findings in patients with long-term normal
      transaminases.
AB  - In this study we aimed to correlate liver histology and the presence of hepatitis
      C virus (HCV) viremia, genotype, and quantity of HCV genome in 19 positive and 11
      RIBA II indeterminate patients presenting persistently normal ALT values over 24
      months before biopsy. In addition, after biopsy serum ALT values were monitored
      monthly for a mean follow-up period of 24.8 months, after which patients were
      reevaluated for RIBA II and the presence of viremia. Sixteen patients (53%) were
      serum HCV-RNA-positive; 13 of them (68%) were confirmed positive and 3 (27%)
      indeterminate on RIBA II. Histology of the HCV-RNA-positive patients showed eight
      cases of CPH (one case of genotype 1a; four cases type 1b; three cases type 2),
      six cases of CAH (three cases type 1b, three cases type 2), one case of CLH (type
      not determined), and one case of normal liver (NL) (type 1b). Histology of the
      HCV-RNA-negative patients showed four cases of CPH, one case of CAH, two cases of
      CLH, and seven cases of NL. During the follow-up period nine patients (30%)
      presented slight increases in ALT values (< 2 x N), and in particular, flares of
      ALT were observed four times in the CAH and five times in the CPH patients, who
      were all viremic, but never in the NL subjects. These results indicate that
      subjects positive on RIBA II, but with persistently normal ALT values, had a high
      probability of being serum HCV-RNA-positive and that almost all these viremic
      subjects presented histologic signs of liver disease. In contrast, RIBA II
      indeterminate subjects had a moderate probability of being HCV-RNA-positive, but
      a number of these may present signs of liver disease. In both cases there was no
      association with genotype or HCV-RNA serum levels. The other nonviremic cases
      included subjects with hepatic changes going toward resolution or with normal
      liver in whom hepatic biopsy can be avoided. Only one case was a true carrier
      since he was viremic with normal liver and persistently normal ALT values.

PMID- 9286240
TI  - Spontaneous rupture of liver in a patient with Ehlers Danlos disease type IV.
AB  - Ehlers-Danlos syndrome (EDS) type IV is an autosomal dominant connective tissue
      disease caused by mutations in the type III collagen gene resulting in extreme
      tissue fragility. Affected individuals are at risk of dramatic and often fatal
      complications, mostly spontaneous arterial, uterine, or colonic ruptures.
      Phenotypic expression of EDS type IV is variable and clinical signs are generally
      quite subtle, thus making a prompt diagnosis difficult. The case of a 33-year-old
      woman is described who presented with a wide range of clinical features and
      sequelae that eventually led to the diagnosis of EDS type IV. She presented with
      spontaneous liver rupture, renal infarction, and pneumothorax, all representing
      rare complications of EDS type IV. Prior history revealed a uterine rupture in
      advanced pregnancy associated with ischemic necrosis of the descending and
      sigmoid colon. EDS type IV should be suspected in young individuals who present
      with such unusual complications. Early diagnosis is essential if severe or even
      lethal complications are to be avoided in the diagnostic and therapeutic
      management of such patients.

PMID- 9286241
TI  - Combined factor IX and XI deficiency discovered at liver biopsy.

PMID- 9286242
TI  - Changes in gastrin and serum pepsinogens in monitoring of Helicobacter pylori
      response to therapy.
AB  - The aims of this study in 50 patients with H. pylori infection and duodenal ulcer
      were to examine the effect of eradication therapy on the serum levels of gastrin,
      pepsinogen I, and pepsinogen II and to investigate whether monitoring of the
      serum changes in these peptides after treatment could predict patient outcome. H.
      pylori status was assessed at entry and one and six months after therapy by
      culturing and microscopic analysis of the gastric mucosa and by [14C]urea breath
      test. Significant decreases were observed in the serum levels of gastrin (-11.4
      +/- 3%), pepsinogen I (-28.9 +/- 4%), and pepsinogen II (-40.4 +/- 3%) in the 45
      patients whose infection was eradicated, but not in the patients without
      eradication. Serum values of these peptides were unchanged in an additional group
      of 10 patients that only received omeprazol, none of whom had H. pylori
      eradicated. The best cutoff point of the percentage of each peptide to predict
      patient outcome was 10% for gastrin and pepsinogen I, and 15% for pepsinogen II.
      A pepsinogen II decrease > 15% resulted in the best marker of H. pylori
      clearance, accurately identifying patient outcome 86.6% of the time, whereas the
      diagnostic accuracy of gastrin and pepsinogen I was 61.7% and 76.6%,
      respectively. Significant correlations were found between the bacterial load
      assessed by histology with the serum concentrations of pepsinogen I and II and
      with the urease activity as measured by the amount of 14CO2 excreted. In
      conclusion, eradication of H. pylori infection is followed by a significant drop
      in serum levels of gastrin, pepsinogen I, and pepsinogen II. Changes in the
      latter are the most uniform and may be used as an indirect tool to predict
      treatment outcome.

PMID- 9286243
TI  - Effect of enprostil on omeprazole-induced hypergastrinemia and inhibition of
      gastric acid secretion in peptic ulcer patients.
AB  - This study was performed to examine the effects of additional enprostil
      administration on hypergastrinemia and gastric acid suppression induced by
      omeprazole. Serum gastrin concentrations were measured in 10 peptic ulcer
      patients (six Helicobacter pylori-positive and four Helicobacter pylori-negative
      patients) before treatment, after two weeks of omeprazole (20 mg/day), and after
      two weeks of omeprazole and enprostil (50 micrograms/day). The additional acid
      inhibitory effect of enprostil was evaluated by 24-hr intragastric pH
      measurements in five healthy Helicobacter pylori-negative volunteers. After
      omeprazole treatment, the serum gastrin level of Helicobacter pylori-positive
      patients (3.5-fold of control) was markedly higher than that of Helicobacter
      pylori-negative patients (1.7-fold of control). Additional treatment with
      enprostil suppressed serum gastrin levels to 0.4-fold and 0.7-fold of omeprazole
      treatment levels in Helicobacter pylori-positive and Helicobacter pylori-negative
      patients, respectively. In healthy volunteers, median pH recorded during the
      nonmeal daytime interval increased significantly with additional enprostil. Thus,
      enprostil reduces undesirable omeprazole-induced hypergastrinemia, especially in
      Helicobacter pylori-positive patients, and effectively suppresses acid secretion.

PMID- 9286244
TI  - Mitogenic properties of human gastric juice.
AB  - This study was performed to define the biologically active growth modulators in
      human gastric juice. Mitogenic activity was evaluated by the incorporation of
      [3H]thymidine into 3T3 fibroblasts. A negative correlation was observed between
      pH and mitogenic activity in gastric juice (r = -0.45, P < 0.01). The
      concentrations of epidermal growth factor (EGF), transforming growth factor-alpha
      and -beta 1 (TGF-alpha and -beta 1), platelet-derived growth factor (PDGF), and
      basic fibroblast growth factor (bFGF) in gastric juice did not explain these
      changes in mitogenic activity. Gel filtration identified growth-stimulating
      activity due to small molecule mitogens (less than 13 kDa), and growth inhibitory
      activity only in neutral samples due to a macromolecular substance (larger than
      240 kDa) susceptible to trypsin digestion and heat and acid treatments. We
      conclude that acidity-dependent changes in mitogenic activity observed in this
      study are due to appearance of acid-unstable, high-molecular-weight, growth
      inhibitory substance.

PMID- 9286246
TI  - Glutathione and N-acetylcysteine reduce gastric mucosal blood flow in rats.
AB  - Glutathione has been studied as a possible mediator in gastric mucosal protection
      and healing, but its extracellular function is not fully understood. This study
      evaluates blood flow changes in normal gastric mucosa secondary to glutathione
      modulation under stable central hemodynamic conditions. Thiol substances were
      quantified by reverse-phase ion-pair liquid chromatography and fluorescence
      detection. Central hemodynamics remained stable when glutathione and N
      acetylcysteine were administered in a dose of 0.5 mmol/kg. Higher doses than 0.5
      mmol/kg of glutathione and N-acetylcysteine caused unstable hemodynamics.
      Glutathione (0.5 mmol/kg intravenously) and N-acetylcysteine (0.5 mmol/kg
      intravenously) reduced corpus mucosal blood flow by 28% and 26% (P < 0.0005),
      respectively, and glutathione reduced antral mucosa blood flow by 22% (P < 0.01).
      L-Buthionine-[S,R]-sulfoximine (2 mmol/kg intravenously) did not effect gastric
      mucosal blood flow. Cysteine content in mucosa and plasma increased while mucosal
      glutathione levels were largely unchanged after administration of reduced
      glutathione and N-acetylcysteine. Plasma glutathione only increased after
      injection of glutathione. L-Buthionine-[S,R]-sulfoximine reduced the glutathione
      level in both plasma and mucosa. We conclude that glutathione and N
      acetylcysteine reduce gastric mucosal blood flow and that the effect may be
      related to increased cysteine levels in plasma or mucosa.

PMID- 9286245
TI  - Changes in sulfated macromolecules produced in vivo during normal and
      indomethacin-delayed ulcer healing in rats.
AB  - The aim of this study was to examine the synthesis of sulfated glycosaminoglycans
      during normal healing of experimental acetic acid-induced gastric ulcer in rats
      and to investigate the effect of indomethacin, a drug known to delay ulcer
      healing, on this synthesis using an in vivo labelling system. Analysis revealed
      the presence of two major sulfated species in control tissue; a population of
      sulfated mucins and glycosaminoglycans, predominantly galactosaminoglycans. The
      incorporation of [35S]sulfate label into glycosaminoglycans synthesized in the
      granulation tissue of healing ulcers increased significantly (P < 0.05) as
      compared to day 0 and control levels at day 14. Treatment of animals with
      indomethacin (1 mg/kg daily) resulted in a further significant (P < 0.01) rise in
      sulfated glycosaminoglycan synthesis in indomethacin-treated ulcer tissue
      compared to that found in healing ulcers at day 14. The increased
      glycosaminoglycan synthesis was due to increased levels of chondroitin sulfate
      and dermatan sulfate. Glycosaminoglycan synthesis is elevated at the ulcer site
      during healing of experimental gastric ulcers; however, indomethacin treatment,
      which delays ulcer healing, significantly increases the synthesis of
      glycosaminoglycans above that seen in healing ulcers. Changes in the sulfated
      glycosaminoglycan content of the ulcer may play a role in the healing process and
      may give further insight into the mechanisms by which indomethacin delays ulcer
      healing.

PMID- 9286247
TI  - Gallstone dissolution with oral bile acid therapy. Importance of pretreatment CT
      scanning and reasons for nonresponse.
AB  - In patients with cholesterol-rich gallbladder stones and a patent cystic duct,
      complete stone clearance rates of 65-90% have been reported with oral bile acids
      (OBAs) alone or with adjuvant lithotripsy (extracorporeal shock-wave lithotripsy;
      ESWL). The aims of the present study were to analyze pretreatment gallstone
      characteristics that predict the speed and completeness of dissolution with OBAs
      +/- ESWL, and to assess, in patients with incomplete dissolution, the reasons for
      the poor response. We compared pretreatment gallstone characteristics in 43
      patients who became stone-free after a median of 9 months OBAs +/- ESWL with
      those in 43 age- and sex-matched patients whose stones failed to dissolve after
      two years of treatment. In those with incomplete gallstone dissolution, we
      repeated the oral cholecystogram and computed tomogram (CT) and, in selected
      patients, obtained gallbladder bile by percutaneous fine-needle puncture. In
      patients who became stone-free, those with stones that were isodense with bile
      and/or had CT scores of < 75 Hounsfield units had the fastest dissolution rates.
      In the 43 nonresponders, the main causes for treatment failure were impaired
      gallbladder contractility and acquired stone calcification. CT-lucent,
      noncholesterol stones, or failure of desaturation of bile with the prescribed
      bile acids, occurred in a minority. We conclude that the pretreatment CT
      attenuation score predicts both the speed and completeness of gallstone
      dissolution. In patients with incomplete stone dissolution, the combination of
      oral cholecystography, CT, and analysis of gallbladder bile will determine the
      underlying reasons for treatment failure in most, but not all, cases.

PMID- 9286249
TI  - Perindopril-induced acute pancreatitis.

PMID- 9286248
TI  - Tissue-specific cytokine production during experimental acute pancreatitis. A
      probable mechanism for distant organ dysfunction.
AB  - Our purpose was to determine if cytokines are produced systemically during acute
      pancreatitis. Proinflammatory cytokines are elevated during acute pancreatitis
      and have been implicated in the progression of pancreatitis-associated multiple
      organ dysfunction. Whether these mediators are produced within all tissues or
      very few specific organs is not known. Edematous pancreatitis was induced in
      adult male mice by IP injection of cerulein. Necrotizing pancreatitis was induced
      in young female mice by feeding a choline-deficient, ethionine supplemented diet.
      Animals were sacrificed as pancreatitis worsened, with multiple organs prepared
      for tissue mRNA and protein analysis by RT-PCR and immunoblotting. Pancreatitis
      severity was established by histologic grading and serum amylase and lipase.
      There was no cytokine mRNA or protein detectable prior to the induction of
      pancreatitis. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL
      1 beta) mRNA and protein were detected within the pancreas early in the course of
      pancreatitis in both models, coinciding with the development of hyperamylasemia
      (both P < 0.001). Interleukin-6 was produced in the pancreas after pancreatitis
      was more fully developed (P < 0.001). IL-1 beta and TNF-alpha were subsequently
      produced in large amounts in lung, liver, and spleen but never within kidney,
      cardiac muscle, or skeletal muscle. A significant delay between pancreatic and
      distant organ cytokine production was always observed. It is concluded that
      proinflammatory cytokines are produced within the pancreas and within organs
      known to develop dysfunction during severe pancreatitis. Cytokine production is
      tissue specific, correlates with disease severity, and occurs within the pancreas
      first and subsequently within distant organs.

PMID- 9286250
TI  - Morphological aspects of necrosis as a guideline for treatment of necrotizing
      pancreatitis. A brief report about 50 patients.
AB  - In a retrospective study, 50 patients with obvious necrotizing pancreatitis (NP)
      were allocated in four groups according to the morphological aspects of the
      necrosis. Appearance of ascite (N1), extrapancreatic spread of necrosis towards
      neighboring organs (N2), a large amount of necrosis (N3), and infected necrosis
      (N4), appears to be an easy and useful guideline for the management of NP
      patients. Organ failures (72%) and mortality rate (36%) are higher when the
      process is infected. In the other groups, organic dysfunctions were frequent, but
      all the patients except one survived. The majority (80%) of patients were
      operated on. Only 20% of patients had successful nonsurgical treatment and they
      were in N3 group. This percentage may increase through a morphological approach
      to treating necrosis, with the use of endoscopic treatment for the disruption of
      pancreatic duct, and better accuracy in the management of patients with
      noninfected necrosis, whenever organ failures are present.

PMID- 9286251
TI  - Usefulness of simple endoscopic aspiration cytology of pancreatic juice for
      diagnosis of early pancreatic neoplasm. A prospective study.
AB  - For detection of early cancer of the pancreas, endoscopic aspiration cytology of
      pancreatic juice without endoscopic retrograde pancreatography was performed in
      64 consecutive outpatients who had symptoms or findings that suggested pancreatic
      disease. Patients with positive or suspicious cytologic results or abnormal US
      findings were admitted and underwent detailed examinations. Positive and
      suspicious cytologic results were obtained in 2 and 10 patients, respectively. Of
      those with positive and suspicious cytologic results, two, and one patient,
      respectively, were ultimately found to have pancreatic neoplasms. Of these three
      resected specimens, one was in situ carcinoma and two presented marked atypia.
      All patients were alive with no evidence of recurrence. No further cases of
      pancreatic neoplasm were found. Complications from the procedure did not develop
      in any patient. This technique is useful in the diagnosis of early neoplasms of
      the pancreas, because it is simple and safe to perform for outpatients.

PMID- 9286253
TI  - Vascular endothelial growth factor. 20th-century mechanisms, 21st-century
      therapies.

PMID- 9286252
TI  - Noninvasive assessment of gastric acid secretion in man. Application of
      electrical impedance tomography (EIT).
AB  - Electrical impedance tomography (EIT) is a tubeless technique that generates
      tomographic images of gastric resistivity. We investigated the application of EIT
      to measure gastric acid secretion. Nineteen normal subjects underwent a standard
      intubation test. Basal acid output (BAO) and stimulated acid output (SAO)
      (millimoles per hour) were measured before and after pentagastrin, respectively.
      On a different day, EIT was performed before (basal) and after pentagastrin
      (stimulated). The changes in impedance over time were measured and the area under
      the curve (AUC) was calculated. Both the tests were repeated in 13 subjects after
      omeprazole treatment. As in the intubation test, there was the expected increase
      in AUC value after pentagastrin (basal vs stimulated; 1.2 +/- 2.8 vs 731 +/- 297,
      P < 0.0001). A significant fall in acid output and AUC following omeprazole
      pretreatment was observed (without vs with omeprazole; 20.5 +/- 5.7 vs 0.03 +/-
      0.06, P < 0.0001 for intubation test and 731 +/- 297 vs 44 +/- 172, P < 0.0001
      for EIT). There was a significant correlation between SAO and the delta AUC with
      (r = 0.65 P < 0.001) or without (r = 0.95, P < 0.001) omeprazole and in all the
      experiments (r = 0.87, P < 0.001). This study demonstrates the predictable change
      of gastric impedance and may be useful as a noninvasive test for measuring
      gastric acid secretion.

PMID- 9286254
TI  - Role of astrocytes in the control of developing retinal vessels.
AB  - PURPOSE: To assess the role of astrocytes in controlling the growth of developing
      retinal vessels. METHODS: Growth of retinal vessels in the neonatal rat retina
      was examined in three conditions: normal development, cyclic hyperoxia, and
      normoxia (1 day 70% to 75% oxygen, 1 day room air for up to seven cycles from
      birth, and room air for up to 16 days), and direct hypoxia (10% oxygen from
      postnatal day 3 [P3]). Retinas were examined as wholemounts labeled for
      astrocytes, microglia, and blood vessels and in some experiments for the
      fragmentation of DNA characteristic of apoptosis. RESULTS: In normoxia,
      superficial retinal vessels formed to the processes of astrocytes. In cyclic
      hyperoxia, the depletion of superficial retinal vessels and subsequent
      neovascularization described by others were confirmed. The neovascularization was
      preceded by the depletion by apoptotic death of the astrocyte population, first
      between vessels but eventually breaching the glia limitans along vessels. The
      earliest forms of neovascularization resembled microaneurysms, each protruding
      through a defect in the glia limitans of a capillary. Neurons of the ganglion
      cell layer survived. Direct hypoxia from P3 caused hypertrophy of superficial
      vessels. Between P3 and P6, some vessels accelerated past the still-spreading
      astrocytes, often growing out of the retina into the vitreous humor. Direct
      hypoxia also caused astrocyte degeneration, but capillaries retained astrocyte
      investment and were not the site of vascular damage. By P8, breaches in the
      astrocytic glia limitans became prominent but were restricted to large veins. At
      such breaches, bleeding into the vitreous humor was common. CONCLUSIONS: Retinal
      vessels normally develop in close association with astrocytes. Where that
      association is broken, preretinal vessels may grow or bleed into the vitreous
      humor. Astrocytes play important roles in constraining retinal vessels to the
      retina and in maintaining their integrity.

PMID- 9286255
TI  - Tissue oxygen during a critical developmental period controls the death and
      survival of photoreceptors.
AB  - PURPOSE: To study the death of photoreceptors in normally developing and
      dystrophic retina and to test the role of hypoxia in causing that death. METHODS:
      Death of photoreceptors was detected in the albino, hooded, and Royal College of
      Surgeons (RCS) strains of rat, and in the rabbit and cat, using the TUNEL
      technique. Retinas of selected ages from animals raised normally and those from
      rat pups raised for periods in hyperoxia (75% oxygen) or hypoxia (10% oxygen)
      were studied. RESULTS: In all species and strains examined, a naturally occurring
      wave of photoreceptor death was detected during the last stages of retinal
      development. In the albino rat, this wave, which began approximately at postnatal
      day 15 (P15) and peaked at P22, was reduced by hyperoxia and was intensified by
      hypoxia, producing a "hypoxic dystrophy" of photoreceptors. In the RCS rat,
      photoreceptor death also commenced at approximately P15 and then proceeded to
      exhaustion. This degeneration was greatly reduced by hyperoxia. In the RCS rat,
      hyperoxia was effective in photoreceptor rescue only during a discrete period,
      from P16 to P22. In the albino rat, the effectiveness of hypoxia in inducing
      photoreceptor death was much greater between P15 and P21 than at earlier ages, or
      in the adult. CONCLUSIONS: During a critical period extending approximately from
      P15 to P22, tissue oxygen levels strongly influence photoreceptor death and
      survival in dystrophic and normally developing strains of rat. This period is
      evident in normal development as a period of naturally occurring photoreceptor
      death and is evident experimentally as a period during which hyperoxia is
      effective in rescuing dying photoreceptors and during which hypoxia is effective
      in inducing death of otherwise viable photoreceptors.

PMID- 9286256
TI  - Fiber cell denucleation in the primate lens.
AB  - PURPOSE: To determine the morphologic and biochemical events preceding the
      breakdown of fiber cell nuclei in the primate lens. METHODS: Monkey lens slices
      were labeled with fluorescent probes and optically sectioned using a confocal
      microscope. The distribution of nuclear histones was visualized by
      immunofluorescence. DNA and cellular membranes were imaged simultaneously by
      staining with SYTO 17 and 3,3'-dihexyloxacarbocyanine iodide, respectively. The
      condition of fiber cell DNA during differentiation was determined by an in situ
      DNA fragmentation assay. The assay was adapted to allow the detection of DNA
      fragments with 3'-OH or 3'-PO4 termini. RESULTS: Monkey lens fiber nuclei passed
      through distinct stages before disintegrating. In the outer cell layers, the
      nuclei were large, smooth, and oval-shaped with prominent nucleoli. Deeper in the
      lens, they had a flattened profile with whorls of membranous material and nucleic
      acid accumulated at one end. At this point, histone immunofluorescence was
      reduced and the nucleoli had a characteristic, spoked appearance. At the border
      of the organelle-free zone, the intracellular membranes (including the nuclear
      envelope) disappeared, and particulate material was released from the nuclei into
      the cytoplasm. This material was stained by SYTO-17 and the DNA fragmentation
      assay, indicating that it contained fragmented DNA with 3'-OH termini.
      CONCLUSIONS: The denucleation process in the primate lens differs from that
      described recently in the embryonic chicken lens. In particular, the extrusion of
      nuclear material and persistence of DNA-rich particles in the fiber cytoplasm are
      novel features. One similarity between the denucleation process in these species
      is the appearance of 3'-OH ends in the DNA after the loss of the nuclear
      membrane.

PMID- 9286257
TI  - Differential expression of fibroblast growth factor receptors during rat lens
      morphogenesis and growth.
AB  - PURPOSE: Fibroblast growth factors (FGF) play important roles in the
      developmental biology of the lens. Recently, it was shown that the expression of
      one of the FGF receptors, FGFR1 (flg; fibroblast growth factor receptor 1), was
      closely associated with the onset of lens fiber differentiation. In this study,
      the expression patterns of three other members of the FGF receptor family were
      analyzed and compared. METHODS: The expression patterns of FGFR2 (bek and
      keratinocyte growth factor receptor [KGFR] variants) and FGFR3 were analyzed by
      in situ hybridization during embryonic and postnatal lens development. RESULTS:
      In the ocular primordia, both FGFR2 variants were detected on embryonic day 12
      (E12) and FGFR3 was detected on E14. From E16 to E20, distinct spatial expression
      patterns became evident within the lens; FGFR3 showed an anteroposterior increase
      in expression, with strongest expression in the outer cortical fibers. In
      contrast, bek showed uniform expression throughout the lens epithelium (including
      the central and germinative zones) and the transitional zone, with a subsequent
      decline in maturing fibers. The KGFR variant of FGFR2 showed strongest expression
      in the early fibers of the transitional zone; its expression in the epithelium
      was weaker in the germinative zone of embryonic and neonatal rats. There was an
      age-related decline in expression of FGFRs after birth-an effect that was more
      marked for FGFR3 than for the FGFR2 variants. CONCLUSIONS: Combined with those in
      a previous study, these results indicate that the FGFR1, bek, KGFR, and FGFR3
      genes exhibit different, yet overlapping, patterns of expression throughout lens
      development and differentiation. The distinct spatiotemporal patterns of
      expression of FGF receptors may play an important role in regulating
      anteroposterior patterns of lens cell behavior.

PMID- 9286258
TI  - Anterior segment physiology after bumetanide inhibition of Na-K-Cl cotransport.
AB  - PURPOSE: To determine the effect of bumetanide inhibition of Na-K-Cl cotransport
      on aqueous humor formation and outflow facility in living cynomolgus monkeys,
      outflow facility in organ-cultured human eyes, and contraction in bovine ciliary
      muscle and trabecular meshwork strips, in vitro. METHODS: Aqueous humor formation
      in monkeys was measured fluorophotometrically for 6 hours, 1 to 6 weeks before,
      immediately after, and 2 to 6 weeks after bumetanide was administered
      intravitreally (final concentration approximately 100 or 500 microM) or
      intravenously (0.01 or 0.03 mg/ kg at 0 and 3 hours). Outflow facility in monkeys
      was determined by two-level, constant-pressure perfusion of the anterior chamber
      for 45 to 60 minutes before and after bumetanide was administered by bolus
      intracameral injection (100 microM, initial anterior chamber concentration) or by
      exchanging the anterior chamber with 2 ml 10, 100, or 500 microM bumetanide.
      Urine volume was measured 3 hours after administration of intravenous bumetanide
      in various diluents. The effect on intraocular pressure in organ-cultured human
      eyes was determined for 48 hours by constant-flow-variable-pressure perfusion
      with 10 microM bumetanide. Contraction of fresh bovine ciliary muscle and
      trabecular meshwork was measured isometrically with a force-length transducer
      system after exposure to 100 microM bumetanide +/-1 microM carbachol. RESULTS:
      The bumetanide concentrations used had little effect on outflow facility or on
      aqueous humor formation in normal monkeys, on intraocular pressure in organ
      cultured human eyes, or on contraction of bovine ciliary muscle and trabecular
      meshwork strips. Intravenous bumetanide increased urine volume, regardless of the
      diluent used. CONCLUSIONS: These results suggest that Na-K-Cl cotransport is not
      involved functionally in regulation of aqueous humor inflow and outflow and in
      contractility of ciliary muscle and trabecular meshwork.

PMID- 9286260
TI  - Different responsiveness to nitric oxide-cyclic guanosine monophosphate pathway
      in cholinergic and tachykinergic contractions of the rabbit iris sphincter
      muscle.
AB  - PURPOSE: In the rabbit iris sphincter muscle, sodium nitroprusside (SNP), a
      nitric oxide (NO) donor, inhibits cholinergic contraction but does not affect
      tachykinergic contraction in vitro. The objectives of the current study were to
      clarify the mechanism for the different responsiveness to NO in cholinergic and
      tachykinergic muscular contractions, and to examine whether the mechanism for NO
      induced inhibition of cholinergic muscular contraction is operative in vivo.
      METHODS: Iris sphincter muscle was dissected from the rabbit eye pretreated with
      or without endotoxin (lipopolysaccharide, LPS) in vivo. Cyclic guanosine
      monophosphate (cGMP) content in the iris sphincter muscle was determined by
      radioimmunoassay. The motor activity of the ring-shaped iris sphincter muscle was
      measured isometrically. Sodium nitroprusside, carboxy-2-phenyl-4,4,5,5,
      tetramethyl-imidazoline-1-oxyl-3-oxide (C-PTIO, a scavenger of NO radicals), and
      8-bromo cGMP (a permeable cGMP analogue) were administered between the first and
      second administrations of carbachol and neurokinin A, both of which had caused
      sustained contraction in the iris sphincter muscle. RESULTS: Sodium nitroprusside
      inhibited the contraction of the iris sphincter muscle caused by carbachol but
      had no effect on the contraction caused by neurokinin A. Application of C-PTIO
      significantly reduced SNP-induced cGMP accumulation in the muscle, as well as the
      SNP-induced inhibition of muscular contraction caused by carbachol. Neither
      carbachol nor neurokinin A influenced SNP-induced cGMP accumulation in the
      muscle. Induction of 8-bromo-cGMP significantly diminished the muscular
      contraction caused by carbachol but not that caused by neurokinin A. In vivo
      pretreatment of the eye with LPS increased, in a time-dependent manner, the cGMP
      accumulation in the iris sphincter muscle, which was significantly inhibited by
      pretreatment of NG-nitro-L-arginine methyl ester (an inhibitor of NO synthesis)
      in vivo. CONCLUSIONS: These results demonstrate that in rabbits the increase in
      cGMP accumulation induced by NO in the iris sphincter muscle is involved in the
      cholinergic contraction but not in the tachykinergic contraction, suggesting that
      different sensitivities to cGMP are essential for the different responsiveness to
      NO. Furthermore, the results of this study showed that the NO-cGMP pathway is
      operative in vivo and regulates iris sphincter muscle tone, at least when the
      eyes are infected with bacteria.

PMID- 9286259
TI  - Response and level of beta-adrenergic, vasoactive intestinal peptide, and PACAP
      receptors during the circadian cycle.
AB  - PURPOSE: To determine whether a nocturnal increase of ciliary process beta
      adrenergic receptor responsiveness can explain the observation that timolol
      decreased the aqueous flow rate and intraocular pressure (IOP) during the night
      but not during the day in rabbits. METHODS: Rabbits were housed in alternating 12
      hour periods of light and dark. In vitro stimulation of tissue cyclic adenosine
      monophosphate (cAMP) levels by isoproterenol (ISO), vasoactive intestinal peptide
      (VIP), pituitary adenylate cyclase activating polypeptide (PACAP), or a soluble
      derivative of forskolin (sFSK) was measured in ciliary processes harvested at mid
      light phase and early and late dark phase. Inhibition of ISO and VIP stimulation
      of ciliary process cAMP by an alpha 2-adrenergic agonist and maximal binding of
      [125I]I-pindolol, [125I]I-VIP, and [125I]I-PACAP in ciliary process membranes
      were measured at the same three times. RESULTS: Although there may have been a
      nocturnal increase in the sensitivity of ciliary process cAMP levels to
      stimulation by ISO, this was not observed consistently, VIP, but not PACAP,
      stimulation increased at night, but there was no change in the response to sFSK.
      Inhibition by apraclonidine of elevated ciliary process cAMP levels was constant
      at all three times. Ligand-binding studies showed little change in ciliary
      process beta-adrenergic, VIP-, or PACAP-receptor levels at the three times.
      CONCLUSIONS: There is no convincing evidence for a nocturnal increase in beta
      adrenergic receptor sensitivity in rabbit ciliary processes that could explain
      the difference between day and night effects of timolol on aqueous flow and IOP.

PMID- 9286261
TI  - Growth of the two layers of the chick sclera is modulated reciprocally by visual
      conditions.
AB  - PURPOSE: Although visual deprivation causes increased ocular elongation and
      myopia in both birds and mammals, changes in sclera appear to be in opposite
      directions. Because avian sclera has a cartilaginous layer as well as the fibrous
      layer found in mammals, we examined whether the scleral responses to various
      visual manipulations differ between the two layers. METHODS: To produce increases
      in ocular elongation and myopia, monocular diffusers or negative lenses were
      fitted to eyes. Conversely, to produce decreases in ocular elongation, diffusers
      were removed (restoring normal vision) or monocular positive lenses were fitted.
      Scleral layers were then dissected apart, and incorporation of labeled precursors
      into glycosaminoglycans (GAGs), DNA, and protein was assessed. Tissue coculture
      experiments were used to assess humoral interactions between scleral layers and
      with the choroid. RESULTS: In the cartilaginous layers, the incorporation of
      label into proteoglycans and DNA was significantly higher in eyes elongating
      faster than normal because of wearing diffusers or negative lenses and
      significantly lower than normal in eyes elongating slower than normal because of
      removal of the diffuser or wearing positive lenses. In the fibrous layers, the
      reverse was the case. Coculturing cartilaginous sclera from normal eyes with
      fibrous sclera from myopic or recovering eyes produced the same increase or
      decrease in sulfate incorporation into GAGs in the cartilaginous layer as though
      the tissue measured was from the animal providing the conditioning tissue.
      Coculturing with choroid, especially from recovering eyes, also inhibited
      cartilaginous sclera. CONCLUSIONS: The fibrous layer of the avian sclera shows
      changes in sulfate incorporation into GAGs during deprivation and recovery from
      deprivation in the same direction as does the mammalian sclera, whereas the
      cartilaginous layer changes in the opposite direction. The responses of the
      cartilaginous layer may be controlled by the fibrous layer, although they are
      influenced by the choroid as well.

PMID- 9286262
TI  - Proteoglycans in the human sclera. Evidence for the presence of aggrecan.
AB  - PURPOSE: The proteoglycans synthesized and accumulated within the adult human
      sclera (aged 50 to 80 years) were identified by their size, glycosaminoglycan
      side chains, and core proteins in an effort to characterize the proteoglycan
      content of the human sclera. METHODS: Sclerae, unlabeled, or radiolabeled in
      organ culture with 35SO4 or 3H-proline, were extracted in 4M guanidine-HCl and
      separated by Sepharose CL-2B and Superose 6 forced-pressure liquid
      chromatography. Peak fractions, identified by glycosaminoglycan content or
      radioactivity, were pooled and subjected to G-50 chromatography or sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis before and after digestion with
      specific glycosidases. Scleral proteoglycan core proteins were identified in
      Western blot analysis using specific antisera to decorin, biglycan, and aggrecan.
      Reverse transcription-polymerase chain reaction analyses were carried out on
      human scleral fibroblast RNA to confirm the transcription of one scleral
      proteoglycan. Proteoglycans were localized on sections of scleral tissue using
      specific antisera. RESULTS: After chromatography on CL-2B, scleral proteoglycans
      could be resolved into three major peaks, PG-1, PG-2, and PG-3. The largest
      scleral proteoglycan, PG-1, contained chondroitin sulfate and keratan sulfate
      glycosaminoglycan side chains. Results of Western blot analyses indicated that
      the core protein of PG-1 is the aggrecan core protein, migrating at approximately
      350 kDa. Reverse transcription-polymerase chain reaction analyses confirmed that
      human scleral fibroblasts transcribe aggrecan in vitro and in vivo. PG-2 and PG-3
      were identified as biglycan and decorin in Western blot analyses using
      antibiglycan and antidecorin antibodies, respectively. Immunostaining results
      indicated that aggrecan, biglycan, and decorin are distributed throughout the
      thickness of the human sclera. CONCLUSIONS: The adult human sclera contains three
      major proteoglycans; aggrecan, biglycan, and decorin. It is likely that these
      proteoglycans contribute to the structural properties of the sclera and that the
      ratios of these proteoglycans will change with age, specific region, and
      condition of the sclera.

PMID- 9286263
TI  - Effect of acute decreases of perfusion pressure on choroidal blood flow in
      humans.
AB  - PURPOSE: To investigate the relationship between choroidal blood velocity
      (ChBVel), blood volume (ChBVol) and blood flow (ChBF) in the foveal region of the
      human ocular fundus and ocular perfusion pressure and to determine whether the
      choroidal circulation has some autoregulatory capacity. METHODS: Measurements of
      ChBVel, ChBVol and ChBF were obtained by laser Doppler flowmetry in healthy
      subjects (age range, 21 to 57 years) with normal eye examination results.
      Measurements were performed at normal intraocular pressure (IOP) and during
      successive step increases in IOP induced by scleral suction. In experiment 1, in
      six eyes (five subjects), the IOP was increased rapidly, in steps of 50 to 100 mm
      Hg of suction pressure, which each lasted approximately 10 seconds to a level
      above diastolic ophthalmic artery blood pressure (IOP = approximately 72 mm Hg).
      In experiment 2, in 14 eyes (seven subjects), the IOP was increased slowly in
      four successive steps at 2-minute intervals to a level of approximately 42 mm Hg.
      We also determined the pulsatility of the flow parameters during the heart cycle,
      pulsatility = 1 - diast value/syst value. RESULTS: For both rates of suction cup
      increase, the relationship between ChBFm (mean ChBF over the heart cycle) and
      mean perfusion pressure was not linear. At high pressure, ChBFm was less affected
      by decreases in the pressure than expected from a passive vascular system. In
      some cases, no change in ChBFm was detectable, although significant changes in
      PChBF occurred. Further decreases in perfusion pressure resulted in a
      proportional decrease in ChBFm. On release of suction, a significant increase in
      ChBFm over baseline value was detectable in experiment 1. CONCLUSIONS: The
      relationship between ChBFm and ocular mean perfusion pressure appears to be
      bilinear and reveals some autoregulation for moderate step decreases in perfusion
      pressure. The temporal characteristics of the ChBFm-response suggest a neural or
      passive hemodynamical process rather than a myogenic or metabolic compensatory
      mechanism.

PMID- 9286264
TI  - Relaxation by bradykinin in porcine ciliary artery. Role of nitric oxide and K(+)
      channels.
AB  - PURPOSE: To assess the effects of K(+)-channel blockers on bradykinin-induced
      relaxations in porcine ciliary artery. METHODS: Vascular isometric forces were
      measured with a myograph system. Ciliary vascular rings were precontracted with
      thromboxane A2 analog (U 46619, 10(-7) M) to assess dose-dependent (10(-10)-3 x
      10(-6) M) bradykinin-induced relaxation after addition of one of the following:
      the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine methyl ester (L
      NAME, 10(-4) M) or inactive enantiomer (D-NAME, 10(-4) M); the nonspecific K(+)
      channel blocker tetra-ethylammonium (TEA, 10(-2) M); or the ATP-sensitive K(+)
      channel blocker glibenclamide (10(-5) M). The effect of TEA on relaxations to the
      NO donor, sodium nitroprusside (SNP, 10(-10)-10(-4) M) was investigated. The
      membrane potential of vascular smooth muscle cells (VSMC) was recorded after
      exposure to bradykinin (2.5 x 10(-7) M). RESULTS: Endothelium-dependent
      relaxations to bradykinin (maximal [max], 99% +/- 3%) were strongly inhibited by
      L-NAME (max, 39% +/- 4%, P < 0.01) and partially by TEA (max, 62% +/- 3%, P <
      0.01) or glibenclamide (max, 77% +/- 4%, P < 0.01). Administration of
      glibenclamide plus L-NAME further suppressed bradykinin-induced relaxation (max,
      23% +/- 6%; P < 0.01), whereas TEA and L-NAME (max, 6% +/- 2%; P < 0.01)
      abolished the relaxation. SNP relaxations were unaffected by TEA. Bradykinin had
      no effect on the membrane potential of VSMC. CONCLUSIONS: In porcine ciliary
      artery, the endothelium-dependent relaxations to bradykinin are primarily
      mediated by NO and involve K(+)-channels. As only relaxations to bradykinin, but
      not those mediated by SNP, were inhibited by TEA, this implies that K(+)-channel
      blockers most likely affect the bradykinin-evoked NO production or release by the
      endothelium.

PMID- 9286265
TI  - Smooth pursuit in twins before and after alcohol ingestion.
AB  - PURPOSE: The influence of genetic factors on characteristics of smooth pursuit
      were evaluated in young adult monozygotic (MZ) and dizygotic (DZ) twins before
      and after the administration of a single dose of ethanol. METHODS: Sinusoidal
      pursuit was recorded using a scleral search coil at frequencies of 0.25 and 0.5
      Hz before and after alcohol consumption. Pursuit gain, interval between saccades,
      saccadic accuracy, and saccadic amplitude were quantified. RESULTS: Alcohol
      consumption reduced pursuit gain and saccadic accuracy and increased the rate and
      amplitude of saccades. Before and after alcohol consumption, the intraclass
      correlations for MZ twins (rMZ) were highly significant for pursuit gain,
      interval between saccades, and saccade amplitude. Corresponding correlations for
      DZ twins (rDZ) were not significant. Heritability values were similar before and
      after alcohol ingestion. CONCLUSIONS: The disparity between rMZ and rDZ suggests
      either multiple gene interactions or common environmental influences for MZ
      twins, greater than those for DZ twins.

PMID- 9286266
TI  - Innervation of extraocular pulley smooth muscle in monkeys and humans.
AB  - PURPOSE: Soft pulleys stabilize paths and determine pulling directions of the
      extraocular muscles (EOMs). This study was conducted to characterize innervation
      of smooth muscles (SMs) supporting these pulleys. METHODS: Cadaveric human and
      monkey orbits were step and serially sectioned for histochemical and
      immunohistochemical staining. Before perfusion, the superior cervical ganglia of
      one monkey had been injected with the anterograde tracer Phaseolus vulgaris
      leukoagglutinin (PHA-L). Immunoperoxidase staining to human SM alpha-actin
      confirmed pulley SM. Monoclonal and polyclonal antibodies were used to
      demonstrate PHA-L, tyrosine hydroxylase, dopamine beta-hydroxylase,
      phenylethanolamine-N-methyltransferase, neuronal nitric oxide synthase (NOS), and
      synaptophysin. The NADPH-diaphorase reaction was also used as a marker for NOS
      and the acetylcholinesterase (AChE) reaction for acetylcholine. RESULTS: Pulleys,
      consisting of collagen and elastin sleeves supported by connective tissue
      containing SM, were observed around rectus muscles of humans and monkeys. The
      human and monkey SM was richly innervated. Axons terminating in motor end plates
      within SM bundles were immunoreactive to PHA-L, tyrosine hydroxylase, and
      dopamine beta-hydroxylase, but not phenylethanolamine-N-methyltransferase,
      indicating innervation of pulley SM from the superior cervical ganglion by
      projections using norepinephrine. Smaller axons and motor end plates were also
      demonstrated in SM, using NADPH-diaphorase and NOS immunoreactivity, indicating
      nitroxidergic innervation, and using AchE, indicating cholinergic parasympathetic
      innervation. The pterygopalatine and, to a lesser extent, the ciliary ganglia,
      but not the Edinger-Westphal nucleus, contained cells immunoreactive to NOS,
      suggesting that nitroxidergic innervation to pulley SM is mainly from the
      pterygopalatine ganglion. CONCLUSIONS: The SM suspensions of human and monkey EOM
      pulleys are similar and receive rich innervation involving multiple
      neurotransmitters. These complex projections suggest excitatory and inhibitory
      control of EOM pulley SM, and support their dynamic role in ocular motility.

PMID- 9286267
TI  - Rod plateaux during dark adaptation in Sorsby's fundus dystrophy and vitamin A
      deficiency.
AB  - PURPOSE: To investigate the transitory plateaux observed during dark adaptation
      after partial bleaches in Sorsby's fundus dystrophy (SFD) and in systemic vitamin
      A deficiency (VAD). METHODS: Psychophysical dark adaptation functions were
      measured after bleaching exposures isomerizing from 2% to 99% of the rhodopsin.
      Narrow-band stimuli of 1.7 degrees diameter and 200 msec duration were presented
      at an eccentricity of 30 degrees. RESULTS: After a full bleach, the patients
      showed typical dark adaptation abnormalities reported for these diseases. The
      cone recovery was slowed, and the time to the rod-cone break was delayed; the
      final phase of rod recovery was also slowed but led to a normal final rod
      threshold. After partial bleaches, short wavelength stimuli produced a biphasic
      recovery function, with an initial rapid component and plateau, followed by a
      subsequent break-off and eventual return to prebleach thresholds. Action spectra
      obtained during the plateaux were consistent with thresholds for shorter
      wavelength stimuli mediated by rods and thresholds for longer wavelength stimuli
      mediated by cones. In the patient with VAD, vitamin A supplementation led to
      accelerated recovery and disappearance of the transitory rod plateaux.
      CONCLUSIONS: The biphasic dark adaptation functions resulting from fractional
      bleaches in SFD and VAD appear superficially similar to the classic biphasic
      adaptation functions obtained with full bleaches. However, thresholds during the
      plateaux are lower than the cone threshold, and action spectra indicate rod
      mediation. These transitory rod plateaux may increase our understanding of the
      normal visual cycle and its perturbation in retinal disease.

PMID- 9286269
TI  - Identification of lutein and zeaxanthin oxidation products in human and monkey
      retinas.
AB  - PURPOSE: To characterize fully all the major and minor carotenoids and their
      metabolites in human retina and probe for the presence of the oxidative
      metabolites of lutein and zeaxanthin. METHODS: Carotenoids of a composite of 58
      pairs of human retinas and a monkey retina were elucidated by comparing their
      high-performance liquid chromatography (HPLC)-ultraviolet/visible absorption
      spectrophotometry (UV/Vis)-mass spectrometry (MS) profile with those of authentic
      standards prepared by organic synthesis. RESULTS: In addition to lutein and
      zeaxanthin, several oxidation products of these compounds were present in the
      extracts from human retina. A major carotenoid resulting from direct oxidation of
      lutein was identified as 3-hydroxy-beta, epsilon-caroten-3'-one. Minor
      carotenoids were identified as: 3'-epilutein, epsilon,epsilon-carotene-3,3'-diol,
      epsilon,epsilon-carotene-3,3'-dione, 3'-hydroxy-epsilon,epsilon-caroten-3-one,
      and 2,6-cyclolycopene-1,5-diol. Several of the geometric isomers of lutein and
      zeaxanthin were also detected at low concentrations. These were as follows: 9-cis
      lutein, 9'-cislutein, 13-cis-lutein, 13'-cis-lutein, 9-cis-zeaxanthin, and 13-cis
      zeaxanthin. Similar results were also obtained from HPLC analysis of a freshly
      dissected monkey retina. CONCLUSIONS: Lutein, zeaxanthin, 3'-epilutein, and 3
      hydroxy-beta,epsilon-caroten-3'-one in human retina may be interconverted through
      a series of oxidation-reduction reactions similar to our earlier proposed
      metabolic transformation of these compounds in humans. The presence of the direct
      oxidation product of lutein and 3'-epilutein (metabolite of lutein and
      zeaxanthin) in human retina suggests that lutein and zeaxanthin may act as
      antioxidants to protect the macula against short-wavelength visible light. The
      proposed oxidative-reductive pathways for lutein and zeaxanthin in human retina,
      may therefore play an important role in prevention of age-related macular
      degeneration and cataracts.

PMID- 9286268
TI  - Dietary modification of human macular pigment density.
AB  - PURPOSE: The retinal carotenoids lutein (L) and zeaxanthin (Z) that form the
      macular pigment (MP) may help to prevent neovascular age-related macular
      degeneration. The purpose of this study was to determine whether MP density in
      the retina could be raised by increasing dietary intake of L and Z from foods.
      METHODS: Macular pigment was measured psychophysically for 13 subjects. Serum
      concentrations of L, Z, and beta-carotene were measured by high-performance
      liquid chromatography. Eleven subjects modified their usual daily diets by adding
      60 g of spinach (10.8 mg L, 0.3 mg Z, 5 mg beta-carotene) and ten also added 150
      g of corn (0.3 mg Z, 0.4 mg L); two other subjects were given only corn. Dietary
      modification lasted up to 15 weeks. RESULTS: For the subjects fed spinach or
      spinach and corn, three types of responses to dietary modification were
      identified: Eight "retinal responders" had increases in serum L (mean, 33%; SD,
      22%) and in MP density (mean, 19%; SD, 11%); two "retinal nonresponders" showed
      substantial increases in serum L (mean, 31%) but not in MP density (mean, -11%);
      one "serum and retinal nonresponder" showed no changes in serum L, Z, or beta
      carotene and no change in MP density. For the two subjects given only corn, serum
      L changed little (+11%, -6%), but in one subject serum Z increased (70%) and MP
      density increased (25%). CONCLUSIONS: Increases in MP density were obtained
      within 4 weeks of dietary modification for most, but not all, subjects. When MP
      density increased with dietary modification, it remained elevated for at least
      several months after resuming an unmodified diet. Augmentation of MP for both
      experimental and clinical investigation appears to be feasible for many persons.

PMID- 9286270
TI  - Using two preferred retinal loci for different lighting conditions in patients
      with central scotomas.
AB  - PURPOSE: Using a scanning laser ophthalmoscope, it was found that some patients
      with relative central scotomas reliably used two different preferred retinal loci
      (PRLs) at different stimulus illuminances. This article describes adaptations in
      a patient's PRL for fixation when dimming the stimulus increased the relative
      scotoma size. METHODS: Twenty-eight patients with macular diseases had their
      dense and relative macular scotoma borders mapped with the scanning laser
      ophthalmoscope. The high-illuminance PRL (PRLhi) and low-illuminance PRL (PRLlo)
      were operationally defined as the PRLs that patients used to fixate a high or low
      illuminance stimulus, respectively. The PRLs' abilities to do visual tasks and
      their characteristics at the corresponding illuminances were assessed. RESULTS:
      The PRL consistently shifted between the PRLhi and the PRLlo as the stimulus
      illuminance was changed. Brightness permitting, the visual system prefers to use
      the PRLhi with generally better performance in visual function such as fixation
      stability. There were no significant differences between the PRLhi and the PRLlo
      in pursuit and saccadic abilities, when assessed by subjective ratings. The
      illuminances that induced shifting ranged from 106 to 3437 trolands. The PRLhi
      was always located within an area of relative scotoma, usually at the fovea or
      just outside a dense scotoma. The PRLlo was located in relatively healthy retinal
      area, and usually below or to the left of the PRLhi in the visual field.
      CONCLUSIONS: In the visual system, two well-defined PRLs can develop when visual
      function is adapting to maculopathy, with the use of each depending on the
      brightness of objects used in visual tasks. Rehabilitation and treatment
      strategies should consider the existence of multiple PRLs.

PMID- 9286271
TI  - Contrast sensitivity loss is coupled with capillary dropout in patients with
      diabetes.
AB  - PURPOSE: To assess the relationship of foveal microcirculation to contrast
      sensitivity function in early diabetes mellitus. METHODS: Twenty patients with
      diabetes with visual acuity of 20/25 or better without clinically significant
      macular edema were evaluated. Measurements of contrast sensitivity at four
      spatial frequencies (3, 6, 12, and 18 cycles/degree [c/deg]), macular capillary
      blood velocity (CBV), capillary density (PIA: perifoveal intercapillary area),
      foveal avascular zone (FAZ), and microaneurysm count were performed. Contrast
      sensitivity data collected from age-matched normal subjects and previously
      published normal angiographic data were used for comparison with our cohort with
      diabetes. RESULTS: The CBV was significantly reduced (P < 0.0001) and PIA and FAZ
      were significantly enlarged (P < 0.0001) when compared with healthy subjects.
      Contrast sensitivity was significantly lower in the group with diabetes at 6 (P =
      0.01) and 12 (P = 0.002) c/deg as compared with healthy control values. FAZ and
      PIA correlated significantly (FAZ; r = -0.60, P = 0.005; PIA; r = -0.54, P =
      0.02) with contrast sensitivity at 12 c/deg. CONCLUSIONS: The alterations of the
      perifoveal network are related to selective disturbances of central visual
      function as measured by contrast sensitivity. In patients with diabetes
      measurement of contrast sensitivity may provide a clinical adjunct in further
      identifying early ischemic diabetic maculopathy.

PMID- 9286272
TI  - Vitreoretinal surgery assisted by the 193-nm excimer laser.
AB  - PURPOSE: Ablating and cutting vitreoretinal membranes using a 193-nm excimer
      laser-based microsurgical system. METHODS: A 193-nm microsurgical system enables
      delivery of the beam into a fluid medium to cut preretinal and subretinal
      membranes. Two patients with proliferative diabetic retinopathy and one patient
      with proliferative vitreoretinopathy were treated with this new device. RESULTS:
      Gentle ablation and cutting of the preretinal and subretinal membranes without
      exerting any traction on or apparent damage to the neighboring tissue was
      achieved. CONCLUSIONS: The technology is applicable to a variety of intraocular
      vitreoretinal surgical procedures.

PMID- 9286273
TI  - Measurement of corneal epithelial permeability to fluorescein. A repeatability
      study.
AB  - PURPOSE: Permeability (Pdc) to sodium fluorescein (F) is a characteristic of the
      barrier function of the corneal epithelium. The repeatability of several in vivo
      fluorophotometric methods used to measure permeability in humans remains largely
      undocumented. This study examines the repeatability of a method based on topical
      instillation of a single drop of F for the quantitative assessment of Pdc.
      METHODS: Nine healthy subjects with no history of ocular disease provided 1 (n =
      1), 2 (n = 1), or 3 (n = 7) repeated measurements of each eye at successive
      visits. After making 3 baseline fluorescence scans centrally through the tear
      film and cornea, 2 microliters of 0.35% F were instilled and 10 fluorescence
      scans were obtained at approximately 2-minute intervals immediately after
      instillation. Subsequently, the eyes were rinsed three times with nonpreserved
      saline and four additional scans were performed. RESULTS: Pdc was calculated by
      dividing the baseline-corrected postrinse stromal fluorescence by the time
      integral of the tear film fluorescence calculated over the 20-minute exposure
      period. After applying a logarithmic transformation to the Pdc estimates, a mixed
      model analysis was used to assess measurement repeatability. On the Pdc scale,
      there is an estimated 95% chance that a second measurement could be as much as
      2.88 times higher or 0.35 times lower than a first measurement. CONCLUSIONS: This
      substantial variability between repeated measurements indicates that the single
      drop procedure is unreliable for monitoring individual patient changes. However,
      with careful sample size planning, this technique can be used in population-based
      research to compare differences in treatment effects between groups of subjects.

PMID- 9286274
TI  - Elevated mRNA expression of brain-derived neurotrophic factor in retinal ganglion
      cell layer after optic nerve injury.
AB  - PURPOSE: Recent studies show that exogenous brain-derived neurotrophic factor
      (BDNF) can promote retinal ganglion cell survival in vivo and in vitro. BDNF is
      expressed by a subpopulation of cells in the ganglion cell layer (GCL). To
      investigate whether endogenous BDNF may play a role in neuronal protection after
      ganglion cell trauma, BDNF expression in the retina was examined after optic
      nerve (ON) injury. METHODS: The optic nerve in Sprague-Dawley rats was crushed
      intraorbitally posterior to the optic disc. For controls, the optic nerve on the
      opposite side in each animal was similarly exposed but was not crushed. After
      intervals of 6 hours to 6 weeks, eye tissues were processed for in situ
      hybridization, Northern blot, and RNase protection assay using radiolabeled rat
      riboprobes. RESULTS: After ON injury, BDNF expression was significantly elevated
      in cells restricted to the GCL, and more cells demonstrated expression of BDNF
      than were observed in the controls. Elevated BDNF expression was first observed
      at 24 hours, peaked at 48 hours, and declined to the basal level 2 weeks after ON
      injury. Quantitative analysis showed a fivefold to sixfold increase in the number
      of BDNF-positive cells and a 54% increase in BDNF signal intensity in individual
      cells in the GCL 48 hours after ON injury. In control retinas without ON injury,
      BDNF expression was localized to some cells in the GCL, as was observed in normal
      eyes without surgery. Northern blot and RNase protection assay demonstrated a 38%
      elevation in BDNF expression above control levels 48 hours after ON injury.
      CONCLUSIONS: These results indicate that cells in the GCL can upregulate gene
      expression of BDNF in response to ganglion cell axonal injury and suggest that
      endogenous BDNF may contribute to a natural neuroprotective process after ON
      injury.

PMID- 9286275
TI  - Expression of major histocompatibility complex molecules in rodent retina.
      Immunohistochemical study.
AB  - PURPOSE: In Lewis rats, S-antigen-induced intraocular inflammation, which occurs
      initially in the retina, is mediated by T cells requiring major
      histocompatibility complex (MHC)-restricted antigen presentation. In such organ
      specific inflammation, antigen presentation may take place at the site of the
      initial inflammatory response. In the present study an attempt was made to
      determine the presence of the putative antigen-presenting cells in the retina of
      rats. METHODS: Six bone marrow chimeras were constructed by transferring 50 x
      10(6) donor [Lewis x Brown Norway, (LBN) F1] bone marrow cells into lethally
      irradiated Brown Norway rats. Three chimeras, 3 Lewis, and 2 Brown Norway rats
      each received intravenous injections of gamma interferon (IFN-gamma) at a dose of
      2 x 10(5) U/rat, 48 and 24 hours before enucleation of the globes. Enucleated
      globes from the 3 remaining untreated chimeras, 21 additional Lewis rats, and 6
      Brown Norway rats served as controls. Retinas from all globes were prepared for
      either wholemount or cryosectioning and were stained using various primary
      antibodies, including anti-Lewis MHC class II (OX3), anti-rat MHC class II (OX6),
      anti-Lewis MHC class I (II-69), anti-rat MHC class I (OX18), anti-macrophage
      complement receptor 3 (OX42), anti-monocytes/macrophages (ED1, ED2, and ED3), and
      anti-glial fibrillary acidic protein (GFAP). Fluorescein-conjugated goat anti
      mouse and rhodamine-conjugated anti-rabbit immunoglobulins were used to detect
      the monoclonal or polyclonal antibodies, respectively. All the specimens were
      examined under Zeiss confocal laser scanning microscopy. The positively stained
      cells were counted for quantitative analysis. RESULTS: Major histocompatibility
      complex class II (OX6)-positive cells were demonstrated in the wholemount retinas
      of IFN-gamma-untreated chimeras, Lewis, and Brown Norway rats. These cells showed
      a dendritic morphology and increased significantly in number in IFN-gamma-treated
      Lewis and Brown Norway rats. Expression of Lewis-specific class I (II-69) and
      class II (OX3) molecules was detected in a few perivascular cells in the retina
      of chimeric rats treated with IFN-gamma. Most dendritic cells in the retina
      expressed the macrophage markers, ED1 and OX42, without IFN-gamma treatment.
      However, vascular endothelia, retinal pigment epithelia, Muller cells, and
      astrocytes stained neither by Class II molecules nor by macrophage markers. The
      vascular endothelium and retinal pigment epithelium was found to express
      constitutively class I molecules (OX18). CONCLUSIONS: A subpopulation of retinal
      microglia can express MHC class II molecules. Only a few of these are derived
      from bone marrow. Retinal microglial cells, particularly those derived from bone
      marrow, may participate in antigen presentation and the subsequent development of
      retinitis, as seen in S-antigen-induced experimental autoimmune uveoretinitis.

PMID- 9286276
TI  - Acanthamoebae bind to rabbit corneal epithelium in vitro.
AB  - PURPOSE: Selection of an appropriate animal model is crucial for the
      investigation of the pathogenesis of Acanthamoeba keratitis. To this end, it has
      been reported that fluorescein isothiocyanate (FITC)-labeled Acanthamoeba
      castellanii bind to human, pig, and hamster corneas, but not to rabbit corneas in
      organ culture. However, 35S-labeled A. polyphaga and A. culbertsoni have been
      found to bind to rabbit corneal epithelium grown in tissue culture. The purpose
      of the current study was to establish whether A. castellanii bind to rabbit
      corneal epithelium in organ culture. METHODS: Two different adhesion assays were
      used to determine whether 35S-labeled and FITC-labeled A. castellanii bind to
      epithelium of corneal buttons in vitro and, if so, whether the binding is
      temperature-dependent, enhanced by injury, and inhibited by specific saccharides.
      Ameba binding to rabbit corneal epithelium was also evaluated by scanning
      electron microscopy. The binding of A. castellanii to corneal epithelium of three
      different species (human, pig, and rabbit) was compared. RESULTS: Both 35S
      labeled as well as FITC-labeled parasites were found to bind to epithelium of
      rabbit corneal buttons in vitro. Although the parasites bound avidly to the
      corneas at 25 degrees C and 35 degrees C, little binding was observed at 4
      degrees C. Injury enhanced the binding. Methyl alpha-D-mannopyranoside, but not
      other saccharides (alpha-L-fucose and beta-galactose), inhibited binding of the
      parasites to the epithelium of rabbit corneas. By scanning EM, A. castellanii
      were found to adhere, invade, and penetrate the epithelium of rabbit corneas.
      Compared with rabbit corneas, ameba binding to pig, and human corneas was only
      1.2 and 1.4 times higher, respectively. CONCLUSIONS: Rabbit animal model may
      prove useful for investigation of the molecular mechanisms that mediate adhesion
      of Acanthamoeba to corneal epithelium.

PMID- 9286277
TI  - Human leukocyte antigen class I expression. Marker of poor prognosis in uveal
      melanoma.
AB  - PURPOSE: Because the expression of human leukocyte antigen (HLA) antigens is
      important for immunologic recognition of tumor cells, we determined expression of
      locus-specific HLA class I antigens in uveal melanoma and tested whether the
      level of HLA expression was related to prognosis or associated with known
      prognostic parameters. METHODS: Expression of HLA-A and -B antigens was
      determined on 30 formalin-fixed and paraffin-embedded sections of uveal melanoma
      by immunohistochemistry with locus-specific monoclonal antibodies and scored
      semiquantitatively. RESULTS: The level of expression of HLA-A and -B varied
      between uveal melanomas. Expression levels of HLA-A and -B were significantly
      correlated (P = 0.02). High HLA-B expression was significantly correlated with
      the presence of epithelioid cells (P = 0.04) in the tumor. Expression levels of
      HLA-A as well as of HLA-B, cell type, mitotic rate, Mib-1 score, and largest
      tumor diameter were significant predictive factors for survival. High expression
      of HLA-A and -B was associated with a decreased survival. Multiple Cox regression
      analysis with stepwise selection of covariates showed that the contribution of
      HLA-A expression to survival (P = 0.0003) exceeded that of tumor diameter (P =
      0.02) and Mib-1 score (P = 0.04). CONCLUSIONS: Lack of expression of HLA-A as
      well as of HLA-B antigens on uveal melanoma is correlated with a better patient
      survival. Our data suggest that shedding of uveal melanoma micrometastases with a
      low expression of HLA class I into the systemic circulation may facilitate their
      removal and prevent the development of metastases. These findings support a
      protective role for natural killer cells in the development of metastatic disease
      in uveal melanoma.

PMID- 9286278
TI  - Phosphatidylinositol 3-kinase in bovine photoreceptor rod outer segments.
AB  - PURPOSE: Phosphatidylinositol 3-kinase (PI 3-kinase) plays important roles in
      mitogenesis, vesicular trafficking, actin rearrangement, and prevention of
      apoptotic cell death in nonocular tissues. This investigation looked for whether
      PI 3-kinase is present in bovine rod photoreceptors and if light has any effect
      on its activity. METHODS: Bleached (BROS) and dark-adapted (DROS) rod outer
      segments were prepared from frozen bovine retinas and immunoblotted or
      immunoprecipitated with antibodies against the regulatory (p85) or catalytic
      (p110) subunits of PI 3-kinase. Kinase activity was measured in the
      immunoprecipitates and the reaction products were identified by high-performance
      liquid chromatography (HPLC). The amount of PI 3-kinase in membrane and cytosol
      fractions was determined by densitometry of immunoblots. RESULTS: Immunoblot
      analysis showed the presence of 85 and 110 kDa proteins in ROS. PI 3-kinase
      immunoprecipitated by anti-p85 antibody converted PI to PI-3-P and PI-4-P to PI
      3,4-P2, as determined by HPLC analysis of the deacylated products. The PI 3
      kinase activity in these ROS preparations was sensitive to wortmannin, a potent
      inhibitor of PI 3-kinase, at low concentrations (IC50 3 nM). Immunoprecipitates
      (IPs) showed activity twice as high in BROS as in DROS. The IPs of ROS membranes
      but not cytosol maintained the light-dark difference. However, measurement of
      anti-p85 and anti-p110 immunoreactivities on western blots of ROS, ROS membranes,
      and ROS cytosol did not show any light-dark differences. CONCLUSIONS: PI 3-kinase
      is present in bovine rod outer segments and its activity appears to be greater in
      light-adapted retinas.

PMID- 9286279
TI  - Characterization of maxi-K-channels in bovine trabecular meshwork and their
      activation by cyclic guanosine monophosphate.
AB  - PURPOSE: Electrophysiological characterization of trabecular meshwork cells and
      investigation of their response to elevation of cytosolic cyclic guanosine
      monophosphate (cGMP). METHODS: Bovine trabecular meshwork cells were cultured
      according to established methods and were studied, using the whole-cell and
      single-channel configurations of the patch-clamp technique. RESULTS: In single
      channel experiments, cells expressed a channel with characteristics typical of
      maxi-K-channels. The channel was densely distributed in the membrane and had a
      high conductance of 326 +/- 4 pS (Pico Siemens) (symmetrical 150 mmol/l KCl; 37
      degrees C) for potassium and negligible conductance for sodium (0.9 +/- 1 pS).
      The open probability could be elevated by depolarization, increasing cytosolic
      calcium, or adding adenosine triphosphate (1 mmol/ l). The channel could be
      blocked by external charybdotoxin (10(-8) mol/1), external TEA+ tetraethyl
      ammonium chloride (1 mmol/l) and by internal Ba2+ (10 mmol/l), whereas external
      Ba2+ and internal TEA+ (10 mmol/l) had no effect. In whole-cell experiments,
      trabecular meshwork cells displayed a strong outward conductance. Part of this
      conductance (35 +/- 5%) could be blocked by charybdotoxin and stimulated by
      ionomycin (10(-5) mol/1). Addition of 8-bromo-cGMP (10(-3) mol/1) stimulated the
      current to 290 +/- 57% (n = 4) of the original level, charybdotoxin led to a
      reduction of this current to 156 +/- 28% of the initial value. CONCLUSIONS:
      Trabecular meshwork cells express maxi-K-channels. These channels can be
      stimulated by raising internal cGMP levels and are known for their importance in
      smooth muscle relaxation. The results in this study supply further evidence that
      trabecular meshwork displays smooth muscle-like properties and contributes to the
      clarification of the mechanism leading to the relaxation of trabecular meshwork
      by nitrate and nonnitrate vasodilatators.

PMID- 9286281
TI  - Endothelial metaplasia in the iridocorneal endothelial syndrome.
AB  - PURPOSE: To test the hypothesis that the aberrant, cytokeratin-expressing cells
      that replace endothelium in the iridocorneal endothelial (ICE) syndrome are of
      endothelial origin. METHODS: Corneas from four patients with Chandler's syndrome
      and three with essential iris atrophy were examined by two-color
      immunofluorescence for simultaneous expression of cytokeratins and two markers of
      endothelial lineage: vimentin and the antigen recognized by the antiendothelial
      monoclonal antibody 2B4.14.1. RESULTS: In six corneas, unequivocal endothelial
      staining for cytokeratins was present; in each of these, cells coexpressing
      cytokeratins and the two endothelial markers were clearly identifiable. In the
      remaining cornea, weak cytokeratin staining that colocalized with vimentin was
      present. CONCLUSIONS: These results lend strong support to the hypothesis that
      the "epithelial-like" endothelial cells in ICE syndrome are cells of endothelial
      lineage rather than heterotopia of epithelial cells; these cells probably arise
      via a metaplastic transformation of preexisting endothelium.

PMID- 9286280
TI  - Genomic organization of the human TIMP-1 gene. Investigation of a causative role
      in the pathogenesis of X-linked retinitis pigmentosa 2.
AB  - PURPOSE: To evaluate the role of TIMP-1 in inherited retinal degeneration.
      METHODS: The genomic structure of the TIMP-1 gene was established and male
      patients with x-linked retinitis pigmentosa 2 from five families were screened
      for sequence alterations by direct sequencing in all exons, exon-intron
      boundaries, and the 5' upstream region of the gene. RESULTS: TIMP-1 appears to be
      expressed in the retina at low levels and consists of six exons spanning a
      genomic region of approximately 4.5 kb on Xp11.23. No disease-specific sequence
      alterations were identified. A site substitution in exon 5 was observed in
      samples from control subjects and patients, but it did not alter the amino acid
      sequence of the protein product. CONCLUSIONS: The results of this study exclude
      mutations in the TIMP-1 coding sequence, splice sites, and the 5' upstream region
      as a cause of retinal degeneration in x-linked retinitis pigmentosa 2. However,
      an as yet unidentified regulatory element that lies outside these intervals may
      be implicated. The role of this tightly regulated protein in the normal
      functioning of the retina has yet to be determined.

PMID- 9286282
TI  - Dexamethasone decreases phagocytosis by human trabecular meshwork cells in situ.
AB  - PURPOSE: To determine the effect of dexamethasone on the phagocytic capacity of
      the human trabecular meshwork. A decrease in meshwork phagocytosis has been
      proposed in the pathogenesis of steroid glaucoma. METHODS: The anterior segments
      of seven pairs of human eyes were placed in perfusion organ culture. One eye of
      each pair received dexamethasone, and the fellow eye served as control. After 21
      days, latex microspheres labeled with fluorescein isothiocyanate and coated with
      antibodies were added to the culture medium. Twenty-four hours later, the eyes
      were fixed, the trabecular meshworks were treated with a rhodamine-labeled
      secondary antibody and sectioned, and the number of ingested beads was determined
      using a laser scanning confocal microscope. Nuclei were counted and used to
      calculate the phagocytic index of each anterior segment (number of ingested beads
      divided by number of nuclei). RESULTS: Ingested beads appeared green and could be
      differentiated from noningested beads, which appeared red, using appropriate
      wavelengths of the laser. Bead ingestion was confirmed with electron microscopy
      and the use of secondary antibody labeled with horseradish peroxidase.
      Dexamethasone decreased phagocytosis by 57%, as shown by the fact that trabecular
      cells in dexamethasone-treated meshworks ingested significantly fewer beads than
      cells in fellow control meshworks (1.5 +/- 0.6 beads/cell versus 3.5 +/- 1.4
      beads/cell; P = 0.008). No evidence of significant migration or loss of
      trabecular cells was noted; the number of trabecular cells appeared similar in
      dexamethasone-treated and control meshworks (144 +/- 36 versus 141 +/- 46).
      CONCLUSIONS: Dexamethasone inhibits phagocytosis by human trabecular meshwork
      cells in perfusion organ culture.

PMID- 9286283
TI  - Diagnostic tests for HIV.

PMID- 9286284
TI  - Samarium-153 lexidronam for painful bone metastases.

PMID- 9286285
TI  - Genetic predisposition to cancer and familial cancer syndromes.
AB  - Approximately 10% to 15% of childhood cancers are hereditary or familial in
      nature. For several genetic disorders, the development of cancer is a secondary
      manifestation of the clinical phenotype, whereas cancer predisposition syndromes
      are generally recognized by the manifestation of characteristic malignancies. The
      study of pediatric cancer and rare hereditary cancer syndromes and associations
      has led to the identification of numerous cancer genes that are known to play
      critical roles in both normal and abnormal cellular growth, differentiation, and
      proliferation. The potential to identify such genetic markers of cancer
      predisposition poses difficult social, legal, and ethical questions in their
      application to clinical practice.

PMID- 9286286
TI  - Oncologic emergencies.
AB  - The prognosis for the child with cancer has improved dramatically over the past
      decades. With this success comes the need for recognition and proper treatment of
      emergencies. Respiratory or circulatory failure may arise from compression of the
      SVC or airway. Epidural spinal cord compression by tumor may lead to irreversible
      paraplegia or urinary incontinence if intervention is not rapid. Raised
      intracranial pressure may be a life-threatening presentation of a brain tumor.
      Bone marrow failure, with anemia and thrombocytopenia, is associated with
      malignant infiltration of the marrow. Hyperleukocytosis carries a high risk of
      thrombotic events if not treated promptly. Coagulation abnormalities are seen in
      many childhood cancers at the time of diagnosis. Life-threatening metabolic
      abnormalities are observed at presentation in children with leukemia and
      lymphoma. Hypercalcemia, although rare, may be a difficult situation to correct.
      Immediate attention to these emergencies and appropriate treatment may save the
      life of a child with cancer or make his or her subsequent course just a little
      smoother.

PMID- 9286288
TI  - Diagnosis and treatment of childhood acute myelogenous leukemia.
AB  - Acute myelogenous leukemia (AML) accounts for about 20% of the acute leukemias
      seen in children. In contrast to childhood acute lymphoblastic leukemia (ALL),
      there has only been a modest improvement in the cure rate of children with AML
      during the past two decades. Approximately 40% of children treated with
      chemotherapy alone are long-term survivors. The outcome is somewhat better for
      those children who are given bone marrow transplants from histocompatible sibling
      donors early in the first remission. During the last decade, however, new
      insights into the molecular basis of AML has increased our understanding of the
      pathogenesis and biology of this group of leukemias and are beginning to provide
      us with new therapeutic strategies.

PMID- 9286287
TI  - Acute lymphoblastic leukemia.
AB  - Advances in the molecular and immunologic characterization of leukemic cells have
      greatly aided the diagnosis and risk assignment of ALL, as well as the monitoring
      of bone marrow samples for minimal residual disease. Currently, 75% of childhood
      cases have biologically and therapeutically relevant genetic abnormalities.
      Although gene discoveries in ALL have not been directly translated into effective
      therapy, there is every reason to believe that this disease will eventually yield
      to molecular intervention. In the meantime, efforts are being made to enhance the
      efficacy of existing regimens while reducing their toxic side effects. We have
      learned, for example, the following: high-dose methotrexate is more effective
      than lower-dose methotrexate, especially for T-cell ALL; patients who need
      drastic adjustment of mercaptopurine dosage due to thiopurine S-methyltransferase
      deficiency can be prospectively identified; dexrazoxane (ICRF-187) could reduce
      anthracycline cardiotoxicity; granulocyte colony-stimulating factor can shorten
      hospital stays for febrile neutropenia after intensive remission induction
      therapy; and prolonged low-dose epipodophyllotoxin treatment may reduce the risk
      of therapy-induced acute myeloid leukemia without compromising treatment
      efficacy. The challenge now is to identify specific treatments for genetically
      defined subtypes of ALL.

PMID- 9286289
TI  - Non-Hodgkin's lymphoma.
AB  - Pediatric lymphomas are the third most common group of malignancies in children
      and adolescents. Unlike lymphomas in adults, pediatric lymphomas are diffuse,
      aggressive neoplasms with a propensity for widespread dissemination.
      Intensification of conventional treatment approaches along with improvements in
      supportive care have resulted in dramatic improvement in event-free survival
      rates of close to 90% in patients with B-cell lymphomas and only slightly lower
      in patients with T-cell lymphomas. Lymphoid neoplasms arise because of genetic
      changes that result in altered growth and differential patterns of lymphoid
      cells. The characterization of these molecular abnormalities and an understanding
      of their consequences has led to new approaches to diagnosis and the detection of
      minimal residual disease and also provides the basis for the future development
      of novel treatment approaches targeted specifically to the neoplastic cells.

PMID- 9286290
TI  - Hodgkin's disease.
AB  - Despite incomplete understanding of the etiology of Hodgkin's disease and its
      malignant cell of origin, the majority of children and adolescents diagnosed with
      Hodgkin's disease will be longterm survivors. Staging and treatment for pediatric
      Hodgkin's disease has evolved over the past 30 years in attempts to reduce late
      treatment sequelae. Today, most children are clinically staged and treated with
      multitreatment chemotherapy, either alone or in conjunction with low-dose,
      involved field radiation therapy. Initial results with "risk-adapted" combined
      modality regimens limiting chemotherapy cycles and radiation doses and volumes
      demonstrate maintenance of cure rates for early stage, favorable Hodgkin's
      disease. Challenges for the future include identification of prognostic factors
      in patients at risk for treatment failure who may benefit from intensification of
      therapy.

PMID- 9286291
TI  - Brain tumors. Challenges and directions.
AB  - Brain tumors account for 20% of childhood cancers and provide a "frontier" in
      which improved disease control and functional outcome require coordinated,
      directed studies in neurosurgery, radiation therapy, and chemotherapy. Among the
      several brain tumor types common in children, the recent experiences in
      medulloblastoma, ependymoma, and tumors occurring in infants and very young
      children are reviewed in the context of recent clinical trials and ongoing
      investigations.

PMID- 9286292
TI  - Biology and treatment of neuroblastoma.
AB  - Neuroblastoma is an enigmatic tumor that has the highest rate of spontaneous
      regression of all human malignant neoplasms, yet has one of the poorest outcomes
      when occurring as disseminated disease in children. The emergence of
      neuroblastoma tumor biology, coupled with age and stage of diagnosis, has allowed
      more accurate routing of patients to risk-related therapy and refining of such
      therapy to minimize treatment for those with low risk for recurrent disease and
      searching out new treatment strategies for patients with high-risk disease.
      Continued assessment of tumor biologic features in all patients will provide new
      insights into tumorigenesis, cell differentiation, and death pathways, resulting
      in the potential for developing newer therapies for patients with high-risk
      disease.

PMID- 9286293
TI  - Wilms' tumor.
AB  - Wilms' tumor is the most common renal malignancy of childhood. Survival rates for
      favorable histology of Wilms' tumor currently approach 90%. Recent advances in
      the molecular genetics of Wilms' tumor have led to insights into the genetic
      factors involved in the development of Wilms' tumor, normal renal development,
      and the mechanisms of tumorigenesis.

PMID- 9286294
TI  - Rhabdomyosarcoma. Biology and treatment.
AB  - Rhabdomyosarcoma is the most common soft-tissue sarcoma of childhood. Recognition
      of specific genetic changes in the two most common subtypes of rhabdomyosarcoma
      has allowed better understanding of the pathogenesis of this disease. In
      addition, identification of prognostic factors and the use of risk-directed
      multimodal therapy have improved the outcome for these patients significantly,
      with cure rates approaching 70%.

PMID- 9286295
TI  - Osteosarcoma.
AB  - Over the last several decades, significant advances have been made in our ability
      to understand and treat osteosarcoma. In this article we describe the diagnosis,
      evaluation, and treatment of patients with this disease. The surgical issues are
      discussed. We review the major clinical trials that have led to our current level
      of understanding. The current studies for the treatment of osteosarcoma are
      described.

PMID- 9286296
TI  - The Ewing family of tumors. Ewing's sarcoma and primitive neuroectodermal tumors.
AB  - There has been an explosion of new knowledge regarding the Ewing family of tumors
      over the past 5 to 10 years. Classical Ewing's sarcoma and PNET are now known to
      be the same tumor with variable differentiation, defined by a translocation
      between the EWS gene on chromosome 22 with one of three ETS-like genes,
      especially the FLI-1 gene on chromosome 11. Molecular techniques used to identify
      this translocation along with the knowledge that the protein product of the MIC2
      gene is highly expressed on the cell surface have greatly improved our diagnostic
      abilities in this family of tumors. Controversy still exists as to whether
      surgery improves event-free survival when compared with radiotherapy in Ewing's
      sarcoma. The high second tumor rate, if nothing else, has started moving many
      physicians to preferentially use surgery when the functional results are
      predicted to be reasonable. The addition of ifosfamide and etoposide to standard
      therapy in Ewing's sarcoma has improved survival for patients without metastases
      at presentation. However, outcome for patients with metastases or who develop
      metastases while on therapy or shortly thereafter remains poor. Preliminary
      reports of better outcome with megatherapy are interesting but not yet
      definitive. The decades ahead will probably see marked changes in therapy for
      Ewing's sarcoma. The unique translocation seen in virtually all of these tumors
      is a potential target for a "magic bullet" therapy, because the protein product
      of this translocation is present only in the malignant cells. Hopefully either
      immune modulation against this unique protein or further knowledge of how to use
      antisense genes will move us toward exquisitely targeted therapy in the Ewing
      family of tumors.

PMID- 9286297
TI  - Bone marrow transplantation for pediatric malignancies.
AB  - Bone marrow transplantation is now being performed in children having a variety
      of hematologic malignancies and solid tumors. Marrow donors for patients with
      hematologic malignancies are usually allogeneic, including HLA-identical
      siblings, one-antigen mismatched family members, unrelated matched donors, or in
      some situations, two- or three-antigen mismatched family member donors. Umbilical
      cord blood is being explored as a source of hematopoietic reconstitution for some
      allogeneic transplants. Recipients with solid tumors most often receive
      autologous marrow or PBSC grafts. Posttransplant complications continue to
      include acute and chronic GVHD, infections, prolonged immunodeficiency, and
      recurrent malignancy. Because children are now surviving longer after
      transplantation, a variety of delayed effects are becoming apparent. These
      include, but may not be limited to, neuroendocrine dysfunction,
      neuropsychological effects, and ocular and pulmonary dysfunction. Secondary
      malignancies are now also becoming apparent, particularly among patients
      surviving more than 10 years after transplantation. Despite these known problems,
      marrow transplantation remains the treatment of choice for patients who relapse
      from conventional chemotherapy and for patients with CML in chronic phase and AML
      in first remission. Research continues to develop methods to decrease
      posttransplant complications and, hence, increase the probability of long-term
      disease-free survival.

PMID- 9286298
TI  - Long-term survivors of childhood cancer. The medical consequences of cure.
AB  - The late effects of cancer therapy are a significant problem and the risk can be
      predicted based on each individual's prior therapy. Although the use of effective
      therapy has led to the development of sequelae involving various organ systems,
      recognition of these complications has led to the design of new therapy targeted
      at minimizing these effects, especially in patients with good risk.
      Unfortunately, the risks of the late effects must be accepted in patients with
      cancers that are aggressive or in advanced stages to maximize the chance for
      cure. Continued education of cancer survivors regarding their risks of late
      effects is essential and gives them the ability to maintain healthy lifestyles,
      avoiding cancer-promoting behaviors such as smoking. It also gives survivors the
      opportunity to participate in screening programs to help in early recognition of
      the late consequences of therapy and to learn self-examination to detect second
      malignancies early. It is hoped that the use of early intervention will lead to
      an improved long-term outcome. Finally, continued surveillance of this population
      is essential to monitor the impact of the therapeutic modifications on late
      complications and potentially to detect the sequelae produced by newer treatment
      strategies. Because the number of childhood cancer survivors will continue to
      increase, it is imperative that the pediatricians and internists in the community
      who care for these survivors are aware of their risks for late effects so that
      they have access to and can benefit from early intervention.

PMID- 9286299
TI  - Legal and societal issues facing survivors of childhood cancer.
AB  - The Boy Scouts have a good motto: Be prepared! Childhood cancer survivors and
      their families--and, if that is their preference, spouses and significant others-
      must learn to become their own best advocates. Life after cancer should be
      attacked with the same determination and perseverance that is allocated to life
      during cancer. Know your resources and how to use them. Learn networking skills
      and establish your own helping network. This article should give you a good
      start. Do not let yourself become a victim. Take charge of your future. Childhood
      cancer survivors are a hardy breed and should be a productive and successful
      force in society.

PMID- 9286300
TI  - Hematopoietic modulation by the tachykinins.
AB  - We have been studying hematopoietic effects by the tachykinins, which like many
      other neuropeptides can be expressed in neural and nonneural tissues. Substance P
      (SP) and neurokinin-A (NK-A), members of the tachykinins are immune and
      hematopoietic modulators. SP and NK-A are derived from the preprotachykinin-I
      gene (PPT-I) through alternate splicing and posttranslational modification. In
      the bone marrow (BM), nerve fibers provide a source of neural SP and the stroma
      provides a source of nonneural SP. The tachykinins interact with each of three
      cloned neurokinin (NK) receptors (NK-1R, NK-2R, NK-3R) with SP and NK-A
      exhibiting binding preferences for NK-1R and NK-2R, respectively. Proliferation
      of myeloid progenitors (CFU-GM) is differentially regulated by SP and NK-A. The
      former enhances the proliferation whereas the latter is inhibitory. The BM stroma
      mediates most of the hematopoietic effects exerted by SP and NK-A partly through
      the induction of cytokines. The proliferative effects of SP correlate with the
      induction of positive hematopoietic growth factors such as IL-3, IL-6, GM-CSF and
      c-kit ligand and the inhibitory effects by NK-A correlate with the induction of
      two negative hematopoietic regulators, MIP-1 alpha and TGF-beta. Intracellular
      signals mediated by NK-1R and NK-2R are part of the mechanism responsible for
      tachykinin-mediated regulation of hematopoiesis. The stimulatory effects on BM
      progenitors mediated by NK-1R can be partly inhibited by NK-2R activation. IL-1
      and other cytokines induced by SP in BM stroma modulate NK-1R induction.
      Furthermore, SP can induce IL-1 type I receptor in stroma. Together, these data
      suggest that the tachykinins and the cytokines interact to regulate
      hematopoiesis. These interactions contribute to hematopoietic regulation by
      mechanisms that involve induction of: (1) tachykinins and cytokines by each
      other; (2) NK-1R by cytokines and (3) cytokine receptor by the tachykinins. These
      studies emphasize that in terms of hematopoiesis, the cytokines and neuropeptides
      are not mutually exclusive factors and thus, the hematopoietic regulatory network
      would be incomplete without the role of neuropeptides being considered.

PMID- 9286301
TI  - Proliferative responses to PHA, anti-CD3 and antigens in patients with
      lymphoproliferative disease of granular lymphocytes. Mannoproteins of Candida
      albicans induce proliferation and cytotoxicity.
AB  - In this paper we investigated the lymphoproliferative and cytotoxic responses of
      peripheral blood mononuclear cells (PBMC) of patients affected with
      lymphoproliferative disease of granular lymphocytes of T cell origin to mitogens
      and antigens. Most patients with lymphoproliferative disease of granular
      lymphocytes (LDGL) showed a severely impaired PBMC proliferative capacity in
      response to phytohemagglutinin, anti-CD3 and tetanus toxoid, an impairment that,
      in the case of anti-CD3 response, appears to be related to a defect of
      phosphorylation in response to triggering. In contrast, at least 50% of the
      patients had normal proliferation in response to a mannoprotein fraction purified
      from Candida albicans. These data suggest that some CD3+ GL from LDGL patients,
      that usually respond poorly to proliferative stimuli in vitro, can be triggered
      to perform these functions by candidal antigens.

PMID- 9286302
TI  - Lymphocyte subsets in experimental hemochromatosis.
AB  - The distribution of lymphocyte subsets in blood, thymus, spleen, mesenteric lymph
      nodes, Peyer's patches and bone marrow was evaluated in an experimental model of
      secondary hemochromatosis in rats. The values of CD2, CD4, CD8, B and NK cells in
      these different lymphoid compartments did not differ between the control group
      and the experimental group. These results suggest that the abnormalities of
      lymphocyte subsets previously reported in patients with secondary hemochromatosis
      may be due to factors other than iron overload.

PMID- 9286303
TI  - Effect of blood substitute, recombinant hemoglobin, on in vivo hematopoietic
      recovery from AZT toxicity.
AB  - We determined the in vivo ability of infused human recombinant hemoglobin 1.1 (hr
      Hb) and erythropoietin to rescue the hematopoietic activity from the suppressive
      effects of AZT in normal and in a murine model of AIDS (MAIDS) mice. Mice were
      fed with AZT for 8 weeks with or without treatment in the last 4 weeks by
      administering various concentrations of hr-Hb and/or erythropoietin (Epo). Blood
      parameters, body weight (BW) and erythroid burst-forming units (BFU-E) for all
      mice were determined. AZT-treated normal and MAIDS mice showed a significant
      decrease in hematocrit (64 and 78.1%), hemoglobin (27.2 and 45.5%), BW (17.5 and
      35.5%), number of white (66.9 and 42.1%) and red blood cells (65.5 and 38%), and
      the number of BFU-E (73 and 59%), whereas the AZT-treated normal and MAIDS mice
      that received hr-Hb (5 mg/kg BW/day) and/or Epo (2 U/mouse/day) showed
      significant alleviation of AZT cytotoxicity. This was evident by the recovery in
      all blood indices examined, the number of BFU-E and the BW of mice treated. BFU-E
      recovery in MAIDS (97%) was greater than that in normal mice (63%) as compared to
      their controls. hr-Hb produced a similar response as the combination, however
      recovery was slightly better with the latter in some hematological parameters.
      Higher concentrations of hr-Hb (10-15 mg) did not result in a more significant
      increase in most blood indices. Our results indicate that infusion with hr-Hb can
      alleviate AZT toxicity in normal and in immunodeficient mice, and that hr-Hb may
      be clinically useful in preventing severe bone marrow depression brought about by
      various drugs or agents such as AZT.

PMID- 9286304
TI  - Effect of alpha-interferon on natural killer cell activity and lymphocyte subsets
      in thalassemia patients with chronic hepatitis C.
AB  - The variation of natural killer (NK) cell activity and lymphocyte subsets 20 h
      after a single test dose of alpha-IFN, was studied in 17 thalassemic patients
      with chronic hepatitis C. All patients had suspended the alpha-IFN therapy at
      least 12 months before the study: 10 were considered responders and 7
      nonresponders. Also NK cell cytotoxicity after in vitro incubation with alpha-IFN
      was studied. The administration of a single dose of alpha-IFN increased NK cell
      cytotoxic activity significantly in the group of responders and in non
      responders; moreover the NK cell cytotoxic activity after alpha-IFN in vitro
      incubation increased both in responders and nonresponders, but to a lesser degree
      than in healthy controls. Absolute values of CD4+ and CD8+ lymphocytes decreased
      significantly only in responders. In conclusion, our data suggest that the
      variation of NK cytotoxic activity and lymphocyte subsets after a test dose of
      alpha-IFN can be considered a parameter related to IFN biological effects.

PMID- 9286306
TI  - Characterization of the molecules involved in the hematopoietic microenvironment
      provided by mouse stromal cell line MC3T3-G2/PA6 using a unique reporter system
      that analyzes the direct cell-to-cell interaction.
AB  - As an approach to characterizing the molecules involved in the hematopoietic
      microenvironment provided by a murine clonal preadipose cell line MC3T3-G2/PA6
      (PA6), we developed a unique system to detect the early phase of signal
      transduction caused by the direct cell-to-cell interaction using the reporter
      plasmid pfosluc2 with the c-fos enhancer/promoter linked with the Photinus
      pyralis luciferase gene. The plasmid pfosluc2 was genetically introduced into a
      mouse myeloid leukemia cell line NFS-60 which showed a growth dependency on
      contact with PA6 cells, and the mechanism by which stromal PA6 cells promote the
      proliferation of NFS-60 cells through the direct cell-to-cell interaction was
      analyzed. The direct cell-to-cell interaction with PA6 cells was found to cause a
      significant c-fos induction to NFS-60 cells within 1 h. Approximately 10(5) cDNA
      clones prepared from PA6 cells were screened for their activity to promote the c
      fos expression in NFS-60 cells through the direct cell-to-cell interaction, and
      13 positive clones were obtained. Of these positive clones, five clones encoded
      the stem cell factor, and the others encoded the hepatocyte growth factor (HGF).
      The c-fos induction caused by the contact with PA6 cells in NFS-60 was completely
      inhibited by addition of both antagonistic anti-c-kit and anti-HGF antibodies.
      These results represent direct evidence for the action of HGF on the
      proliferation of hematopoietic cells through direct cell-to-cell interaction with
      stromal cells. Thus, our developed reporter system can be useful in investigating
      the direct cell-to-cell interaction between stromal and hematopoietic cells.

PMID- 9286305
TI  - Lymphotropic virus infection of peripheral blood mononuclear cells in B-cell non
      Hodgkin's lymphoma.
AB  - Some lymphotropic viruses such as Epstein-Barr virus (EBV) and human herpesvirus
      6 (HHV-6) have been proposed as causative agents of B cell non-Hodgkin's lymphoma
      (NHL). More recently, the presence of hepatitis C virus (HCV), which is both a
      hepatotropic and lymphotropic virus, has been reported in one third of B cell NHL
      patients. The aim of this study was to investigate in a series of B cell NHL the
      prevalence of three lymphotropic viruses, i.e. EBV, HHV-6 and HCV, in peripheral
      blood mononuclear cells (PBMC). Eighteen unselected B cell NHL patients (10 men,
      8 women; mean age 62 +/- 12 years, range 31-77 years; mean disease duration 1.8
      +/- 1.4 years) and 40 age- and sex-matched healthy controls were included in the
      study. In all cases, an acquired-immunodeficiency-syndrome-related lymphoma was
      excluded. By means of the polymerase chain reaction technique, EBV DNA, HHV-6 DNA
      and HCV RNA were detected in PBMC. HCV genomic sequences were significantly more
      frequent in PBMC of NHL patients than in controls (33 vs. 2.5%; p < 0.01); on the
      other hand, in the same two groups EBV DNA (39 vs. 60%; p = not significant) and
      HHV-6 DNA (22 vs. 32%; p = not significant) were present in a comparable
      percentage of individuals in the same two groups. The infection of PBMC by HCV
      alone was present in the majority (5 of 6) of HCV-positive NHL. These data
      support the implication of HCV infection in a statistically significant number of
      B cell NHL, whereas a possible co-operation between HCV and other well-known
      lymphotropic viruses seems to be excluded.

PMID- 9286307
TI  - Increased serum CA125 levels in plasma cell dyscrasias.
AB  - We report 2 cases of plasma cell dyscrasia presenting with significantly elevated
      serum CA125 levels. The serum levels of CA125 from these patients correlated well
      with their serum M-protein levels. One patient had an IgG-kappa type
      extramedullary plasmacytoma with the culture supernatant from lymph node plasma
      cells showing a considerably high level of CA125 activity. The serum IgG fraction
      purified using a protein A column was devoid of any detectable CA125 activity,
      negating that the serum IgG M-protein from this patient might respond with a
      false-positive result in the CA125 immunoradiometric assay. The other patient had
      an IgG-lambda type plasma cell leukemia with the culture supernatant from
      peripheral mononuclear cells also showing a high level of CA125 activity. These
      observations may suggest that in plasma cell dyscrasias the CA125 antigen is
      spontaneously produced by tumor cells.

PMID- 9286308
TI  - Additional chromosome abnormalities in transient abnormal myelopoiesis in Down's
      syndrome patients.
AB  - We report a case of transient abnormal myelopoiesis (TAM) with Down's syndrome.
      As the blast cells had additional chromosome abnormalities (50,XY,+12,+14,+21 x
      2), a possibility of acute leukemia was considered from a cytogenetic point of
      view. But the abnormal clone gradually disappeared without antileukemic
      therapies. Viewing it together with previous reports of TAM with additional
      chromosome abnormalities in Down's syndrome babies, its presence does not
      immediately indicate an aggressive clinical course as in acute leukemia and
      spontaneous complete hematological remission may be achieved. Thus, a careful
      follow-up should precede cytogenetic findings helping to determine the
      therapeutic intervention.

PMID- 9286309
TI  - Littoral cell angioma in a patient with Epstein syndrome.
AB  - A 61-year-old male with Epstein syndrome and chronic renal failure was admitted
      to our institution for kidney transplantation. He was asymptomatic at the time of
      evaluation. Physical examination revealed pallor and marked splenomegaly
      measuring approximately 12 x 10 cm below the left costal margin. Because of this
      finding, and a history of resected non-small lung cancer, a CT scan of the
      abdomen was obtained. This demonstrated massive, diffusely nodular splenomegaly.
      This article describes the histopathologic and immunohistochemical findings of
      littoral cell angioma, a novel splenic tumor. Also, we discuss the differential
      diagnosis and include a description of the imaging study performed. To our
      knowledge, this is the first case report of littoral cell angioma occurring in a
      patient with Epstein syndrome, and the first radiographic appearance of this rare
      tumor.

PMID- 9286311
TI  - Ophthalmic lasers and liability.

PMID- 9286312
TI  - The portrayal of optometry in the media.

PMID- 9286310
TI  - Overproduction of IL-7, IL-10 and TGF-beta 1 in multiple myeloma.

PMID- 9286313
TI  - Laser in situ keratomileusis for the reduction of myopia: an evaluation of
      clinical results.
AB  - BACKGROUND: Laser in situ keratomileusis (LASIK) combines a 30-year-old
      established lamellar keratectomy procedure with the precision of the
      photoablating excimer laser. This procedure is used to reduce moderate myopia and
      astigmatism. METHODS: LASIK was performed on 130 eyes and the visual outcome was
      evaluated. RESULTS: A total of 63 male eyes and 67 female eyes (mean age, 36
      years: range, 19 to 57 years) were evaluated, for a total of 130 eyes. The mean
      preoperative spherical equivalent was -7.450 (range, -3.12 to -13.87 D). The mean
      preoperative cylinder was -1.15 DC (range, plano to -4.50 DC). For 130 eyes,
      after 1 month the mean postoperative spherical equivalent was -0.53 D (range,
      +2.00 to -4.62 D), and the mean postoperative cylinder was -0.33 DC (range, plano
      to -2.75 DC). For 82 eyes, after 3 months the mean postoperative spherical
      equivalent was -0.83 D (range, +1.00 to -4.67 D), and the mean postoperative
      cylinder was -0.41 DC (range, plano to -2.00 DC). For 49 eyes, after 6 months the
      mean postoperative spherical equivalent was -0.84 D (range, +1.00 to -8.25 D),
      and the mean postoperative cylinder was -0.43 DC (range, plano to -1.75 DC). For
      20 eyes, the mean postoperative spherical equivalent after 12 months was -0.72 D
      (range, +0.50 to -2.50 D), and the mean postoperative cylinder was -0.53 DC
      (range, plano to -2.50 DC). CONCLUSIONS: LASIK appears to be an effective
      treatment for the reduction of moderate-to-high myopia.

PMID- 9286314
TI  - Horror fusionis: a report of five patients.
AB  - BACKGROUND: Horror fusionis is an uncommon anomaly and is rarely reported in the
      literature. METHODS: Five adults with long-standing diplopia associated with
      horror fusionis were examined. RESULTS: All patients had strabismus since early
      childhood and had been treated at that time either with surgery, occlusion,
      and/or orthoptics/vision therapy. Prisms could not eliminate the diplopia. Graded
      occlusion was attempted with one patient but was not tolerated. Another patient
      with an asymmetrical dissociated vertical deviation could ignore the second image
      by fixating with the eye with the smaller deviation. Two patients reported the
      diplopia becoming less noticeable over the years. CONCLUSIONS: Because of its
      poor prognosis, the diplopia associated with horror fusionis must be
      differentiated from other types of diplopia occurring in adults with childhood
      onset strabismus.

PMID- 9286315
TI  - Ocular anomalies of individuals with mental illness and dual diagnosis.
AB  - BACKGROUND: Oculo-visual findings commonly associated with persons diagnosed as
      having mental illness and/or dual diagnosis (i.e. mental illness with mental
      retardation) have not been fully investigated. This study determines the most
      common eye and vision anomalies associated with these disorders and discusses the
      similarities and differences between these two unique populations. METHODS: Data
      were obtained by the random selection of 88 patient records from the Illinois Eye
      Institute/Easter Seal Society of Metropolitan Chicago Eye Care and Treatment
      Program (Illinois College of Optometry). Results from the most recent oculo
      visual evaluation were reviewed. Commonly accepted methods of assessing the eyes
      and vision of patients with disabilities were used. RESULTS: Individuals with
      mental illness frequently exhibited uncorrected refractive error, strabismus,
      blepharitis, pigmentary retinopathy, and cataracts. Those with mental retardation
      and mental illness (dual diagnosis) demonstrated similar findings with the
      exception of cataracts. A statistically significant amount of compound
      astigmatism was seen in those with mental illness. CONCLUSIONS: Many of the
      ocular anomalies found among the mentally ill and those with dual diagnosis were
      common to both groups but occurred with different frequencies. Appropriate
      spectacle correction and individually designed therapy programs should play an
      important role in the developmental and intellectual habilitation of these
      patients.

PMID- 9286316
TI  - Can bifocals slow myopia progression?
AB  - BACKGROUND: Retrospective studies have suggested that in children with near point
      esophoria, bifocals can slow myopia progression by about 50 percent. A
      prospective study was conducted to test this hypothesis. METHODS: Thirty-two
      children, all with near point esophoria, were randomly divided into either
      correction with single-vision or with bifocal lenses containing a +1.25 D and.
      Axial length and refraction were measured under cycloplegia every 6 months for 18
      months. Twenty-eight children completed the study. RESULTS: Myopia progressed at
      an equal rate in both groups for the first 12 months. Progression was much faster
      during the first 6 months, which was during the school year, than during the
      second 6 months, which included all of the summer vacation (0.64 D/yr vs 0.29
      D/yr). During the last 6 months, myopia progressed rapidly for children in single
      vision lenses (0.80 D/yr) but slowly for those in bifocals (0.37 D/yr). A
      repeated-measure analysis of variance showed that season of the year had a
      significant effect on myopia progression (p > 0.002) and that the effect differed
      for the two treatment groups (p > 0.043). Over the whole 18-month study, myopia
      progressed at rate of 0.57 D/yr for those in single-vision lenses and 0.39 D/yr
      in those in bifocals (p = 0.26). CONCLUSIONS: Bifocals seemed to slow myopia
      progression in these children with near-point esophoria, although a longer-term
      study with more subjects is needed to confirm this finding. Myopia progressed
      more rapidly during the school year than during summer vacation.

PMID- 9286317
TI  - Problems of refraction after photorefractive keratectomy.
AB  - BACKGROUND: Excimer laser photorefractive keratectomy (PRK) is a refractive
      procedure to correct myopia that is gaining worldwide acceptance. PRK has been
      performed as an open-ended clinical trial since January 1992, and specific
      problems have been encountered in refracting PRK patients. METHODS: A review of
      all cases of PRK performed with at least 1-year follow-up was conducted. Nine
      hundred and seventy-one eyes with myopia ranging from -2.00 to -15.00 diopters
      had preoperative manifest and cycloplegic refraction, and postoperative
      refraction at 3 months after treatment. RESULTS: Refractive difficulty due to
      degradation of the retinoscopic reflex was encountered in patients who developed
      moderate to severe haze (seven eyes). Small ablation zones (5 mm) and decentered
      ablations also contributed to confusion in interpretation of the retinoscopic
      reflex. In addition, excessive accommodation, profound early myopic and
      hypermetropic shifts, postoperative irregular astigmatism and inaccurate
      autorefractometer readings contributed to difficulty in refraction. CONCLUSIONS:
      Laser ablation of the central cornea produces alterations in optical homogeneity
      of the cornea that may cause significant refractive difficulties. Refracting PRK
      patients requires careful and consistent refraction by an experienced
      refractionist, both before and after laser treatment.

PMID- 9286318
TI  - Conjunctivitis associated with fifth disease in a child: a case report.
AB  - BACKGROUND: Erythema infectiosum, fifth disease, is a mildly contagious childhood
      illness that may present with viral conjunctivitis. It is characterized by a
      facial rash with a "slapped-cheek" appearance and "lacy-like" rash on the trunk
      and extremities. Fifth disease is believed to be caused by parvovirus B19.
      METHODS/RESULTS: A case of 10-year-old child with fifth disease and
      conjunctivitis is presented. CONCLUSIONS: The progression, differential
      diagnosis, and management of fifth disease are reviewed.

PMID- 9286319
TI  - [Snake and scorpion envenomation in Tunisia. Tunis, 26-30 January 1995.
      Abstracts].

PMID- 9286320
TI  - The 7th Congress of the International Society of Developmental and Comparative
      Immunology. Williamsburg, Virginia, July 21-25, 1997. Abstracts.

PMID- 9286323
TI  - 8th European Meeting on Hypertension. Milan, Italy, 13-16 June, 1997. Abstracts.

PMID- 9286321
TI  - 2nd European Biophysics Congress. Orleans, France, July 13-17, 1997. Abstracts.

PMID- 9286322
TI  - 32nd Congress of the European Society for Surgical Research (ESSR). Corfu,
      Greece, May 18-21, 1997. Abstracts.

PMID- 9286324
TI  - 8th International Congress on the Menopause. Sydney, Australia, 3-7 November
      1996. Abstracts.

PMID- 9286325
TI  - [Bibliographical index of papers of the journals Archive of Anatomy, Histology
      and Embryology, volumes 92-101, and Morphology, volumes 102-110].

PMID- 9286326
TI  - [Pan European Consensus Meeting on Stroke Management. Helsingborg, Sweden, 8-10
      November 1995. Abstracts].

PMID- 9286327
TI  - Plant Biology '97. Vancouver, British Columbia, Canada, August 6, 1997.
      Abstracts.

PMID- 9286328
TI  - Cumulative indexes--volumes 1-30.

PMID- 9286329
TI  - Dendritic cell development and maturation.

PMID- 9286330
TI  - Generation of mature dendritic cells from human blood. An improved method with
      special regard to clinical applicability.

PMID- 9286331
TI  - Growth and differentiation of human dendritic cells from CD34+ progenitors.
AB  - Human dendritic cells can be generated from bone marrow CD34+ progenitors in the
      presence of GM-CSF and TNF alpha. The addition of a factor like c-kit-ligand
      optimizes the expansion of dendritic cells, as well as the other myeloid progeny
      grown under the same conditions, and facilitates their identification and
      characterization. In contrast to cord blood, where dendritic cells account for
      the majority of the class II MHC positive myeloid progeny, bone marrow CD34(+)
      derived dendritic cells are less frequent than macrophages. When mature
      macrophages are depleted from days 5-6 cultures, terminally differentiated CD14+
      HLA-DR dendritic cells as well as non-monocyte/macrophage CD14+ HLA-DR+ cells can
      be distinguished. The latter are post-CFU, bipotential, intermediate precursors
      that can terminally differentiate into either dendritic cells or macrophages
      depending on subsequent cytokine exposure. Human CD34+ progenitors isolated from
      bone marrow, as well as cord and peripheral blood, include CFU-DC that give rise
      to pure dendritic cell colonies in the combined presence of GM-CSF and TNF alpha.
      The different sources of CD34+ progenitors are not equivalent, however, with
      respect to frequency of CFU-DC growth. Cord blood is relatively enriched for
      dendritic cell progenitors. The developmental relationship of CFU-DC and CFU-GM,
      to the early developing dendritic cells and the bipotential intermediates
      observed in suspension culture, is not yet established.

PMID- 9286332
TI  - CD34+ hematopoietic progenitors from human cord blood differentiate along two
      independent dendritic cell pathways in response to GM-CSF+TNF alpha.

PMID- 9286333
TI  - Myeloid DCs deduced from monocytes. In-vitro and in-vivo data support a monocytic
      origin of DCs.

PMID- 9286334
TI  - Dramatic numerical increase of functionally mature dendritic cells in FLT3 ligand
      treated mice.

PMID- 9286336
TI  - Dendritic-like cells from relB mutant mice.
AB  - Mice deficient in the NF-kappa B transcription factor relB appear to have defects
      in the production of mature dendritic cells, as secondary lymphoid tissues are
      absent, and spleen cells show a significant loss of antigen presenting function.
      Moreover, the thymus appears to be impaired in negative selection, and immune
      responses in vivo are poor. Since dendritic cell precursors such as skin
      Langerhans cells appear to be normal, we sought information on the nature of the
      dendritic cell defect in these mice. Cultures of mutant bone marrow in the
      presence of GM-CSF revealed a delay in the accumulation of cells with dendritic
      cell features relative to controls; however, these cells were nearly as potent on
      a per cell basis as wild type cells in the stimulation of allogeneic mixed
      lymphocyte cultures. Similarly, skin Langerhans cells from mutant mice also
      showed significant ability to stimulate allogeneic T cells in culture. Since
      these findings cannot explain the defect in immune responses and the absence of
      secondary lymphoid tissues, we also looked at the ability of the relB mutant
      dendritic-like cells to form aggregates in vitro with naive syngeneic T cells. In
      this case, while wild type dendritic cells generated compact aggregates with T
      cells, relB mutant cells only formed irregular small aggregates. Thus, while relB
      mutant dendritic-like cells have some functions of mature dendritic cells, other
      functions are deficient. Understanding the role of relB in regulation of these
      functions should lead to a greater understanding of the molecular basis of
      dendritic cell development and function.

PMID- 9286335
TI  - Selective expression of human fascin (p55) by dendritic leukocytes.

PMID- 9286337
TI  - Driving gene expression specifically in dendritic cells.

PMID- 9286338
TI  - Checkpoints and functional stages in DC maturation.

PMID- 9286339
TI  - T cell-mediated terminal maturation of dendritic cells.

PMID- 9286340
TI  - Migration of cultured chimpanzee dendritic cells following intravenous and
      subcutaneous injection.

PMID- 9286341
TI  - The liver sinusoids as a specialized site for blood-lymph translocation of rat
      dendritic cells.

PMID- 9286342
TI  - Regulation of CD44 isoform expression and CD44-mediated signaling in human
      dendritic cells.
AB  - Dendritic cells (DCs) express CD44, a cell surface receptor for the extracellular
      matrix ligand hyaluronate, involved in cell-cell interactions and cell migration.
      Besides the "standard" form of CD44, a variety of splice variants contain an
      additional extracellular region encoded by 10 "variable" exons termed v1 to v10.
      The standard form of CD44 as well as variants containing exon v6 (CD44v6) are
      known to play important roles in the immune system, yet largely unexplored in the
      DC lineage. In this study, we examined the regulation of CD44 isoforms in human
      DCs derived from monocytes cultivated in the presence of GM-CSF and IL-4. We
      found that v3, v6 and v9 variants are all up-regulated upon TNF-alpha stimulation
      of DCs. In addition, we show that stimulation of DCs using anti-CD44 mAbs can
      induce DC agregation, up-regulation of accessory molecule expression and
      secretion of cytokines. A mAb directed against CD44v6 variants was shown to
      mediate some of these effects.

PMID- 9286343
TI  - Mouse spleen dendritic cells. Phagocytic activity and expression of macrophage
      markers.

PMID- 9286344
TI  - Migration of dendritic cells in 3D-collagen lattices. Visualisation of dynamic
      interactions with the substratum and the distribution of surface structures via a
      novel confocal reflection imaging technique.

PMID- 9286345
TI  - Dendritic cells of the murine Peyer's patches colocalize with Salmonella
      typhimurium avirulent mutants in the subepithelial dome.

PMID- 9286346
TI  - The role of CD11c+ cells as possible candidates for immature dendritic cells in
      the murine Peyer's patches.

PMID- 9286347
TI  - The influence of collagen, fibronectin, and laminin on the maturation of
      dendritic cell progenitors propagated from normal or Flt3-ligand-treated mouse
      liver.

PMID- 9286348
TI  - Stimulation of Langerhans cell migration in mice by tumour necrosis factor alpha
      and interleukin 1 beta.

PMID- 9286349
TI  - Langerhans cells require signals from both tumour necrosis factor alpha and
      interleukin 1 beta for migration.

PMID- 9286350
TI  - alpha 6 integrins are required for Langerhans cell migration.

PMID- 9286351
TI  - Functional expression and modulation of C5a receptor (CD88) on skin dendritic
      cells.

PMID- 9286352
TI  - Unilineage dendritic cell cultures generated by purified human hematopoietic
      progenitor cells.

PMID- 9286353
TI  - CD14 is expressed by subsets of murine dendritic cells and upregulated by
      lipopolysaccharide.
AB  - The CD14 surface molecule is predominantly expressed by cells of myeloid origin
      and regarded as a specific marker for macrophages (M phi). Thus, in human
      mononuclear cell preparations, CD14 expression is a widely used parameter to
      distinguish M phi from dendritic cells (DC). Since a murine homologue of CD14 was
      recently identified, this study investigated expression of CD14 by murine M phi
      and DC. Flow cytometry with a monoclonal antibody directed against murine CD14
      revealed that bone marrow-derived DC express CD14 to various extents during
      differentiation. Functionally, CD14high and CD14low DC did not differ
      significantly in their capacity to present alloantigen, protein antigen or
      immunogenic peptide. Furthermore, surface expression of CD14 could be modulated
      by interleukin (IL)-4 and LPS. Incubation of bone marrow-derived DC with IL-4
      (100 U/ml) resulted in downregulation of CD14 surface expression, whereas
      exposure of BmDC to LPS (1 microgram/ml) led to upregulation of CD14. After
      blockage of CD14 molecules by incubation of DC with anti-CD14 antibodies,
      downregulation of LPS triggered IL-1 release could be detected. In addition,
      other M phi markers such as CD11b, F4/80, BM8, and ER-TR9, are also expressed on
      DC. Therefore, we conclude that CD14, like other M phi markers, is expressed on
      murine DC during maturation. Thus, M phi and DC cannot be distinguished by flow
      cytometry using these markers. Moreover, CD14 may be involved in mediating LPS
      induced activation of murine DC.

PMID- 9286354
TI  - TGF-beta 1 dependent generation of LAG+ dendritic cells from CD34+ progenitors in
      serum-free medium.

PMID- 9286355
TI  - A newly identified antigen retention compartment in the FSDC precursor dendritic
      cell line.

PMID- 9286357
TI  - Mechanisms of Fc epsilon RI-IgE-facilitated allergen presentation by dendritic
      cells.

PMID- 9286356
TI  - Mannose receptor mediated uptake of antigens strongly enhances HLA-class II
      restricted antigen presentation by cultured dendritic cells.
AB  - Dendritic cells (DCs) use macropinocytosis and mannose receptor mediated
      endocytosis for the uptake of exogenous antigens. Here we show that the
      endocytosis of the mannose receptor and mannosylated antigen is distinct from
      that of a non-mannosylated antigen. Shortly after internalization, however, both
      mannosylated and non-mannosylated antigen are found in an MIIC like compartment.
      The mannose receptor itself does not reach this compartment, and probably
      releases its ligand in an earlier endosomal structure. Finally, we found that
      mannosylation of peptides strongly enhanced their potency to stimulate HLA class
      II-restricted peptide-specific T cell clones. Our results indicate that
      mannosylation of antigen leads to selective targeting and subsequent superior
      presentation by DCs which may be useful for vaccine design.

PMID- 9286358
TI  - Localization and intracellular transport of MHC class II molecules in bone marrow
      derived dendritic cells.

PMID- 9286360
TI  - Enhanced antigen presenting cell function following in vivo priming.

PMID- 9286359
TI  - Mannose receptor mediated antigen uptake and presentation in human dendritic
      cells.
AB  - In an immature state, dendritic cells (DC) can capture antigen via at least two
      mechanisms. First, DC use macropinocytosis for continuous uptake of large amounts
      of soluble antigens. Second, they express high levels of mannose receptor that
      can mediate internalization of glycosylated ligands. We found that dendritic
      cells can present mannosylated antigen 100-1000 fold more efficiently than non
      mannosylated antigen. Immunocytochemistry as well as subcellular fractionation
      demonstrated that the mannose receptor and MHC class II molecules were located in
      distinct subcellular compartments. These results demonstrate that the mannose
      receptor endows DC with a high capacity to present glycosylated antigens at very
      low concentrations.

PMID- 9286361
TI  - Dendritic cells from mice lacking the invariant chain express high levels of
      membrane MHC class II molecules in vivo.
AB  - We investigated in H-2k mice bearing a genetically disrupted invariant chain (Ii)
      gene, the MHC class II expression and antigen presentation ability of dendritic
      cells (DC) freshly purified from the spleen (SpDC) or derived from bone marrow
      precursors (BMDC) upon treatment with GM-CSF. In the absence of Ii, class II
      alpha/beta heterodimers are expressed on the DC membranes to a similar extent
      than in control mice, in contrast to splenic B cells. Class II molecules
      immunoprecipitated from the plasma membrane of Ii deficient DC are compact
      indicating that the dimers are stabilized by antigenic peptides. Furthermore DC
      from Ii mutant mice are able to present to CD4+ T lymphocytes, epitopes derived
      from the processing of the hen egg lysozyme (HEL) that normally require
      expression of the Ii molecule for presentation by B cells. All together, our
      results show that the antigen processing machinary of DC provides peptides that
      can reach class II molecules and stabilize their conformation in the absence of
      Ii mediated targeting of class II complexes.

PMID- 9286362
TI  - T lymphocyte mediated regulation of costimulator molecule expression on human
      dendritic cells.

PMID- 9286363
TI  - Activation of immature dendritic cells via membrane sialophorin (CD43).

PMID- 9286364
TI  - Processing of exogenous protein antigen by murine dendritic cells for
      presentation to cytotoxic T lymphocytes.

PMID- 9286365
TI  - The TH1 lymphokine interferon-gamma is a potent upregulator of dendritic cells
      with phagocytic capacity in GM-CSF supplemented bone marrow cultures.

PMID- 9286366
TI  - Functional role of CD101 on skin dendritic cells.

PMID- 9286367
TI  - Presentation of tetanus toxoid to autologous T cells by dendritic cells generated
      from human blood. Improved specificity with dendritic cells generated without
      fetal calf serum.
AB  - Dendritic cells (DC) are highly specialised to initiate primary immune responses
      and may therefore serve as natural adjuvant in future strategies for specific
      immunotherapy, e. g. with tumor antigens. The originally developed culture system
      to generate DC from peripheral human blood with GM-CSF and IL-4 was dependent on
      the use of fetal calf serum. We employed such DC as antigen presenting cells in a
      modified lymphocyte proliferation assay to measure the response of autologous T
      cells to tetanus toxoid. However, a substantial proliferative response of T cells
      was also observed in control wells without antigen, i.e. in the setting of a
      syngeneic mixed leukocyte reaction. This makes it difficult, if not impossible,
      to monitor antigen-specific responses in vitro. In a recently developed improved
      method fetal calf serum was replaced by 1% autologous human plasma. Using such DC
      in our lymphocyte proliferation assay background proliferation was markedly
      reduced. T cell responses to tetanus toxoid were strongest when the antigen was
      added to DC three days before cocultivation with T cells. We conclude that DC
      cultured in FCS-free autologous systems, suitable for clinical use, can process
      and present tetanus protein to autologous T cells. Using such DC in a lymphocyte
      proliferation assay may facilitate the measurement of antigen-specific T cell
      responses.

PMID- 9286369
TI  - Constructing artificial antigen-presenting cells from Drosophila cells.

PMID- 9286370
TI  - Role of dendritic cells in induction of tolerance and immunity in vivo.

PMID- 9286368
TI  - The regulation of T cell responses by a subpopulation of CD8+DEC205+ murine
      dendritic cells.

PMID- 9286371
TI  - B7-2+ low density APCS are as effective as B7-2- small resting B cells in
      inducing specific unresponsiveness to minor histocompatibility (miH) antigen(s)
      in vivo.

PMID- 9286372
TI  - An attempt to induce tolerance with infusion of donor bone marrow in organ
      allograft recipients.

PMID- 9286374
TI  - Generation of nitric oxide by mouse dendritic cells and its implications for
      immune response regulation.

PMID- 9286373
TI  - Blocking of the B7-CD28 pathway increases the capacity of FasL+ (CD95L+)
      dendritic cells to kill alloactivated T cells.

PMID- 9286375
TI  - Dendritic cells in the autoimmune insulitis in NOD mouse models of diabetes.

PMID- 9286376
TI  - Dendritic cells in inflammatory responses in the CNS.

PMID- 9286377
TI  - Th-1/Th-2 switch regulation in immune responses to inhaled antigens. Role of
      dendritic cells in the aetiology of allergic respiratory disease.

PMID- 9286378
TI  - Langerhans cells in the TGF beta 1 null mouse.

PMID- 9286379
TI  - Maturation and migration of murine dendritic cells in situ. Observations in a
      skin organ culture model.
AB  - Dendritic cells reside in tissues such as skin in an immature state. Upon
      antigenic challenge they begin to mature and migrate to the draining lymph nodes.
      These processes are still poorly understood. One way to study in situ aspects of
      maturation and migration are skin organ culture models. In an attempt to learn
      more about the relationship between maturation and migration we investigated the
      expression of several marker molecules by immunohistochemistry. Sheets from
      normal murine ear skin and from skin that had been cultured for three days were
      compared. During culture the numbers of epidermal Langerhans cells decreased and
      accumulations of strongly MHC class II-positive cells ("cords") were found in the
      dermis. As compared to untreated skin, the few Langerhans cells remaining in the
      epidermal sheets after 2-3 days expressed increased levels of MHC class II and
      had also upregulated B7-2 (CD86) as described. They did not express the antigen
      recognized by mAb 2A1, a marker for mature dendritic cells. Double-staining of
      dermal sheets after 3 days of culture showed that dendritic cells in the "cords"
      expressed high levels of MHC class II and CD86 but were also reactive with mAb
      2A1. This pattern is identical to those dendritic cells that had emigrated into
      the culture medium over the period of 3 days. Invariant chain (mAb In1) was
      detected at all stages of culture as opposed to isolated epidermal Langerhans
      cells in suspension where invariant chain expression disappears after 3 days of
      culture. We conclude that the up- (class II, B7-2, 2A1) and down-regulation
      (invariant chain) of dendritic cell molecules during migration does not happen in
      a synchronized manner. The molecule recognized by mAb 2A1 seems to appear late in
      maturation.

PMID- 9286380
TI  - Antigen presentation and IL-12 production by dendritic cells in vivo.

PMID- 9286381
TI  - IL-10 prevents the generation of dendritic cells from CD14+ blood monocytes,
      promotes the differentiation to mature macrophages and stimulates endocytosis of
      FITC-dextran.

PMID- 9286382
TI  - Human dendritic/Langerhans cells control growth and differentiation of CD40
      activated B cells.

PMID- 9286383
TI  - Activation of dendritic cells by surrogate T cell interactions leads to enhanced
      costimulation, secretion of TH1-associated cytokines, and CTL inductive capacity.

PMID- 9286384
TI  - Soluble CD16/Fc gamma RIII induces maturation of dendritic cells and production
      of several cytokines including IL-12.
AB  - Fc gamma RIII (CD16), a low affinity FcR which binds IgG-containing immune
      complexes, exists under membrane-associated forms and under a soluble form (sFc
      gamma RIII). The latter, present in biological fluids (serum, saliva), is
      generated by proteolytic cleavage of the two membrane-associated Fc gamma RIII
      isoforms, Fc gamma RIII-A (expressed by macrophages and NK cells) and Fc gamma
      RIII-B (expressed exclusively by neutrophils). Herein we demonstrate that
      dendritic cells (DCs), generated by culturing monocytes with GM-CSF and IL-4,
      bind biotinylated recombinant sFc gamma RIII. This binding is specific and
      involves the complement receptor CR3 (CD11b/CD18) and CR4 (CD11c/CD18). Indeed,
      preincubation of DCs with anti-CD11b and anti-CD11c mAbs decreased by 52% and 62%
      respectively the binding with sFc gamma RIII. Moreover, electron microscopy
      showed that binding of gold-labeled sFc gamma RIII to DCs maintained at 4 degrees
      C occurred within clathrin-coated pits. Once internalized, at 37 degrees C, sFc
      gamma RIII entered the endocytic pathway and reached the MHC class II
      compartments. Furthermore, DCs incubated for 48 h with multivalent sFc gamma RIII
      expressed increased levels of CD40, CD80, CD86, CD54, CD58, HLA class I and class
      II molecules and decreased levels of CD23 and CD32. These effects result in an
      increased capacity of DCs to trigger proliferative responses by CD4+ CD45RA+
      allogeneic T cells. RT-PCR amplification demonstrated that incubation of DCs for
      20 h in the presence of multivalent sFc gamma RIII induced the appearance of GM
      CSF and IL-12 p40 mRNA. Among the cytokines constitutively expressed, IL-1 beta
      and IL-8 were strongly up-regulated whereas IL-6 and IL-12 p35 mRNA were
      increased to a lesser extent and the expression of MIP-1 alpha mRNA remained
      constant. Finally, ELISA tests demonstrated that DCs incubated with multivalent
      sFc gamma RIII secreted the cytokines IL-1 beta, IL-6, IL-8, GM-CSF and IL-12
      p75. Thus, while becoming internalized sFc gamma RIII could affect the capacity
      of DCs to present antigens and, via the induction of accessory molecules and the
      release of the IL-12 p75 protein, could initiate Th1 type immune response.

PMID- 9286385
TI  - Induction of Fc epsilon RI alpha mRNA and protein synthesis by interleukin 4 in
      CD34+ cells-derived CD1a+ dendritic cells.

PMID- 9286386
TI  - FACS-sorted spleen and Peyer's patch dendritic cells induce different responses
      in Th0 clones.

PMID- 9286387
TI  - Dendritic cells, obtained from peripheral blood precursors in the presence of
      PGE2, promote Th2 responses.
AB  - In order to investigate the impact of an inflammatory mediator PGE2 on the
      functions of maturing DC we used an in vitro model of DC generation from
      peripheral blood monocytes. Addition of PGE2 (10(-9) M-10(-6) M) to the cultures
      performed in the presence of GM-CSF and IL-4 did not alter the morphology nor
      high levels of expression of class II MHC and co-stimulatory molecules on arising
      DC, although at concentrations above 10(-8) M, the acquisition of CD1a was
      selectively prevented. Control DC and the DC maturing in the presence of PGE2
      (PGE2-DC) induced a similar proliferation of naive Th cells. Control DC produced
      high amounts of IL-12, and only trace amounts of IL-10, whereas PGE2-DC produced
      no IL-12 and high levels of IL-10, when stimulated after the removal of PGE2. The
      deficient IL-12 production by PGE2-DC was observed after stimulation both in the
      absence and in the presence of IFN gamma, and was not compensated during further
      48 h culture in the absence of PGE2. Compared to control DC, PGE2-DC induced
      development of Th cells secreting elevated amounts of IL-4 and IL-5, from naive
      precursors. These data indicate that elevated tissue levels of PGE2 may promote
      type 2 Th responses by impairing the ability of locally maturing DC to produce IL
      12. Since Th2 responses mediate protection in Th1-related autoimmune disorders,
      the use of PGE2-DC in immunotherapy of such disorders may be considered.

PMID- 9286388
TI  - Dendritic cells and macrophages induce the development of distinct T helper cell
      populations in vivo.

PMID- 9286390
TI  - Dendritic cells as immunogens for human CTL responses.
AB  - The cellular requirements for generating potent human CD8+ CTLs to influenza A
      virus in vitro have been defined. Furthermore, we have developed improved methods
      for generating large numbers of DCs from non-proliferating progenitors. These
      developments have enabled the design of new strategies to elicit CTLs in vivo.
      For example, together with IL-12, antigen-pulsed DCs may be a useful approach for
      boosting CTL responses against infectious agents and malignancies. Our results
      also reopen the potential use of inactivated virus preparations as immunogens for
      CTL responses.

PMID- 9286389
TI  - A potential pathway of Th2 development during primary immune response. IL-10
      pretreated dendritic cells can prime naive CD4+ T cells to secrete IL-4.

PMID- 9286391
TI  - Dendritic cells as targets for cytotoxic T lymphocytes.
AB  - Dendritic cells (DC) carry antigen into lymph nodes where they may cluster with
      CD4 and CD8+ lymphocytes and activate both subsets in the initiation of immune
      responses. Since DC do not leave the lymph nodes in the efferent lymph they may
      die within the lymph nodes. Another possibility is that they are targets for
      cytotoxic T cells (CTL) when expressing appropriate epitopes. This possibility
      was tested in vitro using human peripheral blood DC to stimulate the development
      of primary CTL in response to HIV-1 or one of its T-cell epitopes (e.g. env 111
      126) and secondary CTL in response to type A influenza virus. Pooled CTL
      generated during six day cultures in 60 replicate 20 microliters hanging drops
      were tested in a conventional CTL assay. The HIV or HIV peptide stimulated CTL
      lysed HIV infected DC while the influenza-virus induced CTL killed DC targets
      infected with this virus. DC were not lysed significantly until they had been
      exposed to virus for 2-3 days and thus are not highly susceptible to lysis.
      However, killing of DC after 2-3 days infection with virus may be a feedback
      mechanism for removing antigen presenting cells after they have stimulated T cell
      responses. Removal of persistently infected DC by CD8+ CTL may also contribute to
      the reduction in DC numbers observed in blood and skin in HIV infection.

PMID- 9286392
TI  - Cutaneous dendritic cells promote replication of immunodeficiency viruses.
AB  - The cutaneous or mucosal DC-T cell environments seem extremely supportive of
      immunodeficiency virus replication. Apart from very early after SIV infection,
      similar virus producing cells have been difficult to detect in the lymphoid
      tissues where DCs and T cells are also known to interact. Large amounts of virus
      can be visualized in the germinal centers of the lymph nodes, much of which
      represents immune complexed virus that is trapped on the follicular dendritic
      cell surface. However, whether these virus-carrying cells actually make virus or
      even virus proteins requires further investigation. We believe that once an
      individual is systemically infected, free virus and/or virus-infected cells will
      seed peripheral tissues and when encountering similar DC-T cell environments as
      described in the oral mucosae, can set up sites of chronic virus replication. For
      instance, a virus-carrying T cell that migrates to the periphery would, on
      entering this milieu, interact with the mature DCs and activate virus production.
      This likely occurs at similar sites around the body, such as the mucosal
      associated lymphoid tissue of the gut, and is probably independent of the route
      of infection.

PMID- 9286393
TI  - Dendritic cells express and use multiple HIV coreceptors.

PMID- 9286394
TI  - In vitro HIV infection of dendritic cell precursors. Effect on dendritic cell
      differentiation and function.

PMID- 9286395
TI  - The role of dendritic cells in the transport of HIV to lymph nodes analysed in
      mouse.

PMID- 9286396
TI  - The HIV-1 life cycle is blocked at two different points in mature dendritic
      cells.

PMID- 9286397
TI  - Infection of human dendritic cells by measles virus induces immune suppression.

PMID- 9286398
TI  - Immortalized cell lines with dendritic morphology derived from mice lacking both
      type I and type II interferon receptors present MHC II restricted antigen to T
      cells and induce mixed leukocyte reactions.

PMID- 9286399
TI  - Infection of human thymic dendritic cells with HIV-1 induces the release of a
      cytotoxic factor(s).

PMID- 9286400
TI  - Dendritic cell surface molecules. A proliferating field.

PMID- 9286401
TI  - Analysis of dendritic cells at the genetic level.
AB  - To increase our understanding of dendritic cell (DC) function we have used two
      approaches to search at the genetic level for molecules which are specifically
      expressed by these cells. First, we have performed random sequencing of cDNA
      libraries prepared from DC. Second, we have employed differential display PCR (DD
      PCR). DD-PCR is a powerful technique for the identification at the RNA level of
      molecules which are expressed in a cell type-specific manner. In our study, we
      have compared RNA from DC with RNA from a panel of leukocyte cell lines. Here we
      present a summary of our findings using these two approaches, and show that both
      methods are complementary and can be used to identify molecules that are specific
      to DC.

PMID- 9286402
TI  - Subtractive cDNA cloning. A new approach to understanding dendritic cell biology.

PMID- 9286403
TI  - Increased level of phosphotyrosine in human dendritic cells under stimulation
      with contact sensitizers but not irritants.

PMID- 9286404
TI  - Insulin-like growth factor type I (IGF-I) supports growth of V-relER dendritic
      cell progenitors.

PMID- 9286406
TI  - Differential gene expression in cultured human Langerhans cells in response to
      phagocytic stimulation.

PMID- 9286405
TI  - Differential mRNA expression in untreated and TNF-alpha elicited murine dendritic
      cells precursors.
AB  - We have compared the pattern of gene expression in long term cultured precursor
      dendritic cells (DC), either untreated (immature) or cultured for two days in the
      presence of recombinant murine (rm)-TNF alpha (mature). The hybridization
      signature of complex cDNA probes prepared from total RNA extracted from immature
      and mature DC were analyzed using a mouse thymic cDNA library, gridded on high
      density filters. For each clone spotted on the filters, we have measured using an
      imaging plate device the hybridization signals of the complex probe obtained from
      immature or mature DC. Comparative analysis of these values allowed us to
      identify differentially expressed gene products. Our goal is to identify a new
      set of genes induced or repressed during DC maturation elicited by rmTNF alpha
      treatment.

PMID- 9286407
TI  - Isolation of differentially expressed genes in epidermal Langerhans cells.

PMID- 9286408
TI  - Absence of follicular dendritic cells (FDC) in mutant mice with deficient
      TNF/lymphotoxin (LT) signaling.

PMID- 9286409
TI  - A role for CR2 in FDC-B cell interactions.

PMID- 9286410
TI  - Disappearance of the antigen exchanging ability of FDC induced by repeated
      antigen injections.

PMID- 9286411
TI  - In vitro priming to tumor-associated proteins.

PMID- 9286412
TI  - Development of dendritic cell-based genetic vaccines for cancer.

PMID- 9286414
TI  - Tumor-infiltrating dendritic cells are defective in their antigen-presenting
      function and inducible B7 expression. A role in the immune tolerance to antigenic
      tumors.

PMID- 9286413
TI  - Immunotherapy of cancer. Generation of CEA specific CTL using CEA peptide pulsed
      dendritic cells.
AB  - Antigen specific cytotoxic T lymphocytes (CTL) are being studied for their
      potential immunotherapeutic benefit in the treatment of cancer. Carcinoembryonic
      antigen (CEA) is an oncofetal protein best known for its overexpression in the
      majority of colorectal, gastric, pancreatic, non small cell lung, and breast
      carcinomas. We are using dendritic cells (DC) pulsed with the CEA CTL peptide
      epitope to generate CEA specific CTL. DC from HLA A2+ donors were isolated by
      culturing plastic adherent PBMC in GMCSF and IL4 for 7 days. As expected these DC
      expressed the relevant cell surface molecules including HLA DR, CD58, CD80, and
      CD86. The DC were stripped of their endogenous peptides, pulsed with the A2
      restricted CEA peptide, irradiated and used to stimulate autologous CD8+ T cells
      in the presence of IL7. Using this approach we have been able to generate CEA
      specific CTL from the PBMC of breast and pancreatic carcinoma patients as well as
      HLA A2+ tumor cells expressing the CEA antigen. This data is being used to
      support a phase I active immunotherapy clinical protocol using DC pulsed with CEA
      peptide to treat patients with metastatic malignancies expressing CEA.

PMID- 9286416
TI  - Positive and negative regulation of dendritic cell function by lipopolysaccharide
      in vivo.

PMID- 9286415
TI  - Role of B7 costimulation in the induction of T and B cell responses by dendritic
      cells in vivo.

PMID- 9286417
TI  - Dendritic cells induce immunity to cutaneous leishmaniasis in mice.

PMID- 9286418
TI  - Immune response in dendritic cell depleted mice.

PMID- 9286419
TI  - Dendritic cell based therapy of cancer.

PMID- 9286420
TI  - Identification and isolation of CD1a positive putative tumour infiltrating
      dendritic cells in human breast cancer.
AB  - Identification of dendritic cells (DC) in human tissues has been technically
      problematic due to the lack of truly specific immunohistochemical markers for
      DC's. Human dendritic cells express CD1a glycoprotein at certain points in their
      life cycle. CD1a positive cells are present in many human tumours and have been
      associated with improved survival. However, little information exists concerning
      the separation of DC from human tumours. The current study reports that human
      breast carcinomas have low densities of CD1a positive cells with dendritic
      morphology, and details are shown of a technique for successful separation of
      these cells from tumour tissues.

PMID- 9286421
TI  - Dendritic cells and interleukin 12 as adjuvants for tumor-specific vaccines.

PMID- 9286422
TI  - Generation of in vitro autologous human cytotoxic T-cell response to E7 and HER
      2/neu oncogene products using ex-vivo peptide loaded dendritic cells.

PMID- 9286423
TI  - Brain tryptophan perturbation in hepatic encephalopathy: implications for effects
      by neuropsychoactive drugs in clinical practice.

PMID- 9286424
TI  - Hepatic encephalopathy in acute liver failure: role of the glutamate system.

PMID- 9286425
TI  - Glutamate and muscarinic receptors in the molecular mechanisms of acute ammonia
      toxicity and of its prevention.

PMID- 9286426
TI  - Studies on the pharmacological properties of oxindole (2-hydroxyindole) and 5
      hydroxyindole: are they involved in hepatic encephalopathy?

PMID- 9286427
TI  - The involvement of ammonia with the mechanisms that enhance GABA-ergic
      neurotransmission in hepatic failure.

PMID- 9286428
TI  - Direct enhancement of GABA-ergic neurotransmission by ammonia.

PMID- 9286429
TI  - The peripheral benzodiazepine receptor and neurosteroids in hepatic
      encephalopathy.

PMID- 9286430
TI  - Ornithine aminotransferase as a therapeutic target in hyperammonemias.

PMID- 9286431
TI  - Sparse-fur (spf) mouse as a model of hyperammonemia: alterations in the
      neurotransmitter systems.

PMID- 9286433
TI  - Hyperammonaemia without portal systemic shunting does not resemble hepatic
      encephalopathy.

PMID- 9286432
TI  - Abnormal gene expression causing hyperammonemia in carnitine-deficient juvenile
      visceral steatosis (JVS) mice.

PMID- 9286435
TI  - Osmosignalling and osmolytes in liver and astrocytes.

PMID- 9286434
TI  - Magnetic resonance spectroscopy in the study of hyperammonemia and hepatic
      encephalopathy.

PMID- 9286436
TI  - Effects of acid-base alterations and protein depletion on hepatic nitrogen
      metabolism.

PMID- 9286437
TI  - Glucose and insulin metabolism in cirrhosis.

PMID- 9286438
TI  - An ammonia hypothesis of Alzheimer disease.

PMID- 9286439
TI  - Living related liver transplantation.

PMID- 9286440
TI  - Genetic drift. The awful truth.

PMID- 9286441
TI  - The ornithine transcarbamylase (OTC) gene: mutations in 50 Japanese families with
      OTC deficiency.
AB  - Mutations in the OTC gene in 50 Japanese families with OTC deficiency were
      reviewed in relation to the phenotype of the patients and predicted structure of
      the mutant enzyme. Similar to other X-linked diseases, mutant alleles in OTC
      deficiency are highly heterogeneous. Mutations observed in male patients with
      neonatal onset of the disease included base insertion/deletion, exon skipping,
      and nonsense and missense mutations in exon 4, 5, 6, or 7. OTC activity was
      essentially undetectable in this group of patients. These mutations possibly
      resulted in unstable mRNA or truncated protein, or involved the active site or
      core domain of the enzyme leading to structural changes. In male patients with
      late onset, abnormalities observed were missense mutations in exons 2, 4, 8, 9,
      and 10, and missense mutations plus donor site errors involving exons 4, 5, and
      6. OTC activity in these patients was 8.1 +/- 6.3% of the control and most
      mutations occurred on the surface of the protein. In female patients, age at
      onset ranged from 19 months to 7 years, depending on residual OTC activities (4.5
      to 33% of the control). Most mutations in this group were similar to those seen
      in male patients with neonatal onset, i.e., nonsense and missense mutations in
      exons 5 and 6, and exon skipping, leading to null enzyme activity. These
      collective data can serve for genetic counseling and monitoring in prenatal care.

PMID- 9286442
TI  - Functional methionine synthase deficiency due to cblG disorder: a report of two
      patients and a review.
AB  - Functional methionine synthase deficiency due to abnormal methylcobalamin
      metabolism causes megaloblastic anemia, moderate to severe developmental delay,
      lethargy, and anorexia in association with homocystinuria. Patients with this
      disorder of cobalamin metabolism can be classified into two separate groups, cblE
      or cblG, primarily on the basis of complementation analysis with cultured skin
      fibroblasts. We describe two unrelated boys, ages 3 and 5 years, with the cblG
      defect in methylcobalamin synthesis. Both children presented with severe
      developmental delay, lethargy, anorexia, and megaloblastic anemia. The diagnosis
      of homocystinuria was delayed in each case due to difficulties with detection of
      small amounts of homocystine in physiologic samples. The clinical course of cblG
      disease is favorably altered by treatment with intramuscular hydroxycobalamin.
      Megaloblastosis in the presence of adequate supplies of cobalamin and folate in
      the blood must alert the clinician to the possibility of functional methionine
      synthase deficiency and should prompt a careful search for associated biochemical
      hallmarks, including homocystinuria/emia.

PMID- 9286443
TI  - Severe cervical dysplasia and nasal cartilage calcification following prenatal
      warfarin exposure.
AB  - We present an infant who was exposed to warfarin throughout pregnancy and has
      warfarin embryopathy. When the child was examined radiologically at 20 months
      areas of calcification were visible in the septal and alar cartilages of the
      small external part of the nose. The location of this ectopic calcification is
      consistent with that seen in an animal model of the warfarin embryopathy. It
      supports the hypothesis that warfarin interferes with the prenatal growth of the
      cartilaginous nasal septum by inhibiting the normal formation of a vitamin K
      dependent protein that prevents calcification of cartilage. The child also had
      severe abnormalities of the cervical vertebrae and secondary damage to the spinal
      cord. Cervical vertebral anomalies are a relatively common finding in the
      warfarin embryopathy and in the related Binder syndrome.

PMID- 9286444
TI  - Barraquer-Simons syndrome (with sensorineural deafness): a contribution to the
      differential diagnosis of lipodystrophy syndromes.
AB  - Among the lipodystrophies, the Barraquer-Simons syndrome is a rare condition. We
      describe a 27-year-old woman with progressive loss of subcutaneous fat after 15
      years first affecting the face and spreading to the upper part of the body. She
      also suffered from deafness and had marked changes in cranial MRI. We discuss
      possible differential diagnosis such as the Cockayne, SHORT and Berardinelli-Seip
      syndrome.

PMID- 9286445
TI  - Arthrogryposis multiplex congenita, craniofacial, and ophthalmological
      abnormalities and normal intelligence: a new syndrome?
AB  - We report on an 8-year-old boy with clinical manifestations suggestive of a new
      arthrogryposis syndrome. These included characteristic craniofacial
      abnormalities, cleft palate, arthrogryposis multiplex congenita, pulmonary
      hypoplasia, cryptorchidism, and unusual ophthalmological findings. There was no
      intrauterine growth retardation or decreased fetal movements. Despite the poor
      prognosis expected in early life, the patient presented with normal mental
      capability on follow-up. Family data showed that a maternal first cousin of the
      mother (mother's brother's son) had similar findings and died in infancy.
      Differential diagnosis included Pena-Shokeir syndrome or phenotype, Gordon
      syndrome, Marden-Walker syndrome, and the syndrome of arthrogryposis with
      ophthalmoplegia and retinopathy. The possibility of autosomal dominant
      inheritance with reduced penetrance is suggested for this apparently new
      syndrome.

PMID- 9286446
TI  - Mosaic trisomy 22: a case presentation and literature review of trisomy 22
      phenotypes.
AB  - In a case of mosaic trisomy 22 the trisomic cells were detected primarily in
      fibroblasts. Results of initial lymphocyte chromosome analysis were normal.
      However, mosaicism was suspected because the patient had hypomelanosis of Ito,
      hemiatrophy, failure to thrive, and mental retardation. Mosaicism was confirmed
      in cultured fibroblasts. Repeat cytogenetic analysis of peripheral blood
      demonstrated a low level of trisomic metaphase cells, which was confirmed by
      interphase fluorescent in situ hybridization (FISH) analysis. Molecular studies
      supported maternal disomy in the child's disomic cells. The phenotype of this
      condition overlaps that of non-mosaic trisomy 22 chromosome mosaicism in general
      and to some extent the Ullrich-Turner syndrome phenotype. Improved cytogenetic
      and molecular techniques now allow better delineation of aneuploidy syndromes.
      Molecular and FISH studies added information about this case (mosaicism and
      uniparental disomy) not appreciated by routine cytogenetic analysis of
      lymphocytes. The detection of low-level mosaicism and/or uniparental disomy in
      such cases may change the clinical classification and our understanding of
      pathogenesis and recurrence risk of these disorders.

PMID- 9286447
TI  - Rubinstein-Taybi syndrome: objective evaluation of craniofacial structure.
AB  - Rubinstein-Taybi syndrome (RTS) is a rare multiple congenital anomaly syndrome
      comprising mental and growth retardation, broad thumbs and great toes, and an
      unusual face. The classical facial appearance is well-established, striking and
      easy to recognize. It includes downslant of the palpebral fissures, epicanthic
      folds, ptosis, strabismus, highly arched palate, simple ears and a small mouth.
      The nose is distinctive with a beaked appearance, broad fleshy bridge, deviated
      septum and short low columella. Previous studies have documented considerable
      change in this facial phenotype with time. In this study, we evaluated 31
      individuals with RTS from Great Britain and The Netherlands. They range in age
      from 1 to 39 years. Detailed craniofacial measurements were obtained on each
      subject and composite pattern profiles were compiled. There was remarkable
      concordance of patterns at all ages from infancy to adulthood. Microcephaly was
      present consistently. The head was relatively round with head width equal to head
      length. There was narrowness at the skull base with relative broadening of the
      minimal frontal diameter and lower facial width. The mouth was small and ears
      were broad and short. Eyes were wide-spaced in comparison to upper facial width
      and head circumference. The child under 4 years demonstrated some differences.
      Width and depth of the upper face exceeded that of the lower face, whereas with
      increasing age, mandibular dimensions were closer to normal than their maxillary
      counterparts. Despite these differences, the similarity of the profiles of all
      age groups seems to belie the phenotypic changes that can be appreciated
      subjectively. This suggests that major components of the change in appearance are
      those which have not been assessed in this study, such as palpebral fissure
      slant, deviation of the nasal bridge, presence of epicanthal folds or ptosis; or
      for which norms are not available, for example, beaking of the nose, and low
      nasal septum.

PMID- 9286448
TI  - Growth hormone insufficiency associated with haploinsufficiency at 18q23.
AB  - Growth hormone insufficiency is a common cause of growth failure in children with
      the 18q- syndrome. Individuals with this syndrome have a deletion as large as 36
      Mb from the long arm of chromosome 18. We have evaluated 33 children with this
      syndrome for growth hormone production and have identified a region of
      approximately 2 Mb, which is deleted in every growth hormone insufficient
      patient. Two genes contained in this region, myelin basic protein, and the
      galanin receptor, are candidate genes for the growth hormone insufficiency
      phenotype.

PMID- 9286449
TI  - A case with mosaic di-, tetra-, and octacentric ring Y chromosomes.
AB  - A newborn female infant presented with abnormalities of the external genitalia
      including a 3 x 1 cm phallic structure, a perineal urethral opening, bifid
      scrotum, and a single urogenital opening. Peripheral blood karyotype was
      45,X[81]/46,X,+r(Y)[19], however, there were no signs of Ullrich-Turner syndrome.
      High resolution G-banding as well as C- and Q-banding did not demonstrate any
      specific banding pattern or presence of heterochromatin on the ring. However, it
      was noticed that some of the rings were larger than others. FISH with a probe for
      Yq12 was negative in all metaphases studied. A Y-specific paint probe hybridized
      to the entire ring chromosome, confirming its origin. PCR analysis showed the
      presence of the SRY locus and of proximal Yq locus DYS271. Triple color FISH with
      probes for the Y centromere, DYZ5 (Yp), and all human telomeres showed the
      existence of different types of rings, some dicentric, some tetracentric, and
      some probably octacentric. Owing to the increased risk for gonadoblastoma, a
      surgical removal of the gonads was performed.

PMID- 9286450
TI  - Apparently balanced t(1;7)(q21.3;q34) in an infant with Coffin-Siris syndrome.
AB  - Coffin-Siris syndrome is a multiple anomaly/mental retardation syndrome
      characterized by "coarse" facial appearance, hypoplastic or absent nails on the
      fifth digits, generalized hirsutism with sparse scalp hair, hypotonia, and
      developmental delay. Due to several reports of affected sibs with or without a
      mildly affected parent, both autosomal recessive and autosomal dominant
      inheritance have been suggested. All previous patients with well-documented
      Coffin-Siris syndrome are chromosomally normal, and the gene has not been mapped.
      We report on an infant with typical findings of Coffin-Siris syndrome who also
      has a de novo apparently balanced translocation of chromosomes 1 and 7, karyotype
      46,XY,t(1;7)(q21.3;q34). The parental chromosomes are normal and none of the
      relatives have signs of Coffin-Siris syndrome. The breakpoints 1q21.3 and 7q34
      are suggested as possible locations for a Coffin-Siris gene.

PMID- 9286451
TI  - Occurrence of congenital heart disease in children with Brachmann-de Lange
      syndrome.

PMID- 9286452
TI  - An apparently acentric marker chromosome originating from 9p with a functional
      centromere without detectable alpha and beta satellite sequences.
AB  - Recently, we studied a patient with minor abnormalities and an apparently
      acentric marker chromosome who carried a deleted chromosome 9 and a marker
      chromosome in addition to a normal chromosome 9. The marker was stable in mitosis
      but lacked a primary constriction. The origin of the marker was established by
      fluorescent in situ hybridization (FISH) using a chromosome 9 painting probe.
      Hybridization of unique sequence 9p probes localized the breakpoint proximal to
      9p13. Additional FISH studies with all-human centromere alpha satellite,
      chromosome 9 classical satellite, and beta satellite probes showed no visible
      evidence of these sequences on the marker [Curtis et al.: Am J Hum Genet 57:A111,
      1995]. Studies using centromere proteins (CENP-B, CENP-C, and CENP-E) were
      performed and demonstrated the presence of centromere proteins. These studies and
      the patient's clinical findings are reported here.

PMID- 9286453
TI  - High proportions of mtDNA duplications in patients with Kearns-Sayre syndrome
      occur in the heart.
AB  - Kearns-Sayre syndrome (KSS) is a sporadic multisystem mitochondrial disorder
      characterized by progressive external ophthalmoplegia, pigmentary retinopathy,
      onset before age 20, and severe cardiac conduction defects that can lead to
      death. KSS patients harbor partial deletions of mitochondrial DNA (delta-mtDNA),
      sometimes associated with the corresponding mtDNA duplication (dup-mtDNA). As
      reports on the distribution of dup-mtDNAs among KSS tissues are scarce, we
      searched for the presence of dup-mtDNAs in different autopsy tissues of two such
      patients, one of whom carried the so-called "common deletion." Using a newly
      developed long polymerase chain reaction (PCR) protocol in conjunction with
      Southern blot analyses, we found dup-mtDNAs in most of the examined tissues from
      both patients. The proportion of dup-mtDNA in these tissues was much lower than
      the proportion of delta-mtDNA, with one notable exception: in both patients, we
      found an unusually high level of dup-mtDNA in the heart. These data suggest that
      dup-mtDNAs may be more stable in heart tissue of KSS patients than in other long
      lived postmitotic tissues.

PMID- 9286454
TI  - High resolution characterization of an interstitial deletion of less than 1.9 Mb
      at 4p16.3 associated with Wolf-Hirschhorn syndrome.
AB  - Wolf-Hirschhorn syndrome (WHS) caused by 4p16.3 deletions comprises growth and
      mental retardation, distinct facial appearance and seizures. This study
      characterized a subtle interstitial deletion of 4p16.3 in a girl with mild
      retardation and possessing facial traits characteristic of WHS. The patient had
      generalized seizures in conjunction with fever at 3 and 5 years of age.
      Fluorescence in situ hybridization (FISH) with a series of markers in the 4p16.3
      region showed that the interstitial deletion in this patient was between the
      probes D4S96 and D4S182, enabling the size of the deletion to be estimated as
      less than 1.9 Mb. This is the smallest interstitial deletion of 4p16.3 which has
      been reported. The patient contributes to a refinement of the phenotypic map of
      the WHS region in 4p16.3. The critical region for the characteristic facial
      changes of WHS, failure to thrive and developmental delay is now localized to a
      region of less than 700 kb. The mental retardation of this patient was mild
      suggesting that small interstitial deletion may have less severe phenotypic
      consequences.

PMID- 9286455
TI  - Microcephaly with agenesis of corticospinal tracts and arthrogryposis,
      hypospadias, single umbilical artery, hypertelorism, and renal and adrenal
      hypoplasia--previously undescribed syndrome.
AB  - We describe a small, term, male infant with corticospinal tract aplasia secondary
      to motor cortex dysplasia from a neuronal proliferation and/or migrational
      defect. The infant also had microdolichocephaly, sloping forehead, hypertelorism,
      flat nose, apparently low-set ears, micrognathia, arthrogryposis without muscle
      wasting, cortical thumbs, rocker-bottom feet, scoliosis, single umbilical artery,
      and hypospadias with chordee. Oligohydramnios was present prenatally. Neurologic
      examination showed a comatose state, seizures, minimal spontaneous movement,
      minimal response to pain, and absent primitive reflexes. At autopsy, hypoplasia
      of kidneys and adrenal glands was found. There was no aqueductal stenosis or
      pulmonary hypoplasia. Chromosomes were apparently normal. These manifestations do
      not correspond to those of any recognized syndrome; therefore, this patient may
      represent a previously undefined syndrome.

PMID- 9286456
TI  - Molecular cytogenetic characterization of 18;21 whole arm translocation
      associated with monosomy 18p.
AB  - Monosomy of the entire short arm of chromosome 18 as a result of an
      18;acrocentric whole arm translocation has been reported in over 20 patients, 3
      of which were familial. The centromeric origin in de novo cases has not been
      characterized. We report molecular cytogenetic studies of two prenatally-detected
      de novo cases. Amniocenteses were performed because of sonographic findings of
      fetal holoprosencephaly. Cytogenetic studies and dual color fluorescence in situ
      hybridization using Oncor alpha-satellite probes for D18Z1 and D13Z1/D21Z1 showed
      monosomy 18p with presence of a dicentric 18;21 chromosome in both cases
      [45,XY,dic(18;21)(p11.1;p11.1)]. In one case, a second cell line was found, which
      contained 46 chromosomes with a del(18)(p11.1) and an apparently telocentric 21
      not present in either parent [46,XY,del(18)(p11.1),del(21)(p11.1)]. The
      del(18)(p11.1) contained only the 18 alphoid sequence and the telocentric 21
      contained only the 21 alphoid sequence. No centromeric break was detected. We
      propose that the second cell line arose from dissociation of the dic(18;21) with
      no centromeric DNA break. In addition to our case, there have been three previous
      reports of dissociation of dicentric 18;acrocentric chromosomes indicating that
      the translocation site can be unstable and dissociate.

PMID- 9286457
TI  - New gene for autosomal recessive non-syndromic hearing loss maps to either
      chromosome 3q or 19p.
AB  - Autosomal recessive non-syndromic hearing loss (ARNSHL) is the most common form
      of prelingual inherited hearing impairment. A small consanguineous family with
      this disorder was ascertained through the Institute of Basic Medical Sciences in
      Madras, India. Conditions such as rubella, prematurity, drug use during
      pregnancy, perinatal trauma, and meningitis were eliminated by history.
      Audiometry was performed to confirm severe-to-profound hearing impairment in
      affected persons. After excluding linkage to known DFNB genes, two genomic DNA
      pools, one from the affected persons and the other from their non-affected
      siblings and the parents, were used to screen 165 polymorphic markers evenly
      spaced across the autosomal human genome. Two regions showing homozygosity-by
      descent in the affected siblings were identified on chromosomes 3q21.3-q25.2 and
      19p13.3-p13.1, identifying one (or possibly both) as the site of a novel ARNSHL
      gene.

PMID- 9286458
TI  - Hardikar syndrome: a new syndrome with cleft lip/palate, pigmentary retinopathy
      and cholestasis.
AB  - We present a child with a remarkable constellation of abnormalities comprising
      cleft lip and palate, pigmentary retinopathy, hydronephrosis, malrotation of the
      gut and obstructive liver disease. This patient, together with two other reported
      cases, seems to represent a new syndrome with some similarities to the Kabuki
      syndrome.

PMID- 9286459
TI  - Leukodystrophy incidence in Germany.
AB  - Through a survey of all departments of pediatrics, neurology and neuropathology
      in Germany, we calculated the incidence of all major forms of leukodystrophy.
      Only diagnoses based on specific biochemical tests in association with typical
      findings and/or neuroradiologically proven white matter involvement were
      accepted. In accordance with these strict criteria, 617 cases of leukodystrophy
      were found (incidence of all forms: app. 2.0/100,000). Minimal incidence was
      estimated at 0.8/100,000 for adrenoleukodystrophy/adrenomyeloneuropathy
      (ALD/AMN), 0.6/100,000 for metachromatic leukodystrophy (MLD), and 0.6/100,000
      for Krabbe disease. Thus ALD/AMN is apparently underdiagnosed in Germany. A
      considerable proportion of leukodystrophies could not be classified in spite of
      adequate diagnostic procedures in experienced centers.

PMID- 9286460
TI  - Interstitial deletion 2q33.3-q34 in a boy with a phenotype resembling the Seckel
      syndrome.
AB  - A boy presented at 5 weeks with a syndrome of pre- and postnatal growth
      retardation, microcephaly, muscular hypotonia, and facial anomalies resembling
      those seen in Seckel syndrome or microcephalic primordial dwarfism I. Analysis of
      prometaphase chromosomes, fluorescent in situ hybridization (FISH), and molecular
      studies showed the presence of a de novo chromosome 2 deletion that could be
      defined as del(2)(q33.3q34)pat. Parental chromosomes were normal, except for the
      presence of a paternal supernumerary marker identified by FISH as der(15). On
      follow-up of the patient during the next months length development appeared
      normal and the diagnosis of Seckel syndrome was withdrawn. Clinical findings of
      previously published cases with interstitial deletion of at least 2q33.3-q34, the
      deletion present in the propositus, are reviewed and include pre- and postnatal
      growth retardation, psychomotor retardation, microcephaly, micrognathia, and
      abnormal/low-set ears; findings also present in the propositus. These findings
      resemble those described in the Seckel syndrome. Noteworthy is the finding that
      2/3 of the 60 reviewed cases originally reported as having Seckel syndrome
      apparently belong to a heterogeneous group of low birth weight microcephalic
      dwarfism I yet to be clearly defined. In these patients no chromosome 2q deletion
      has been reported so far. Retrospective analysis could show if a subgroup of
      these patients carry submicroscopic deletions at 2q33.3-q34. Alternatively,
      molecular analysis of this region may be warranted in newly diagnosed patients
      with Seckel syndrome-like manifestations.

PMID- 9286461
TI  - Cerebellar and brainstem "atrophy" in a patient with Kabuki make-up syndrome.

PMID- 9286462
TI  - Arthritis associated with deletion of 22q11.2: more common than previously
      suspected.

PMID- 9286463
TI  - Deletion of PTEN in a patient with Bannayan-Riley-Ruvalcaba syndrome suggests
      allelism with Cowden disease.
AB  - We report on an 18-month-old boy with an interstitial deletion at 10q23.2-q24.1.
      This region includes the PTEN gene, mutations of which have been reported to
      cause Cowden disease. Our patient presented with manifestations of Bannayan-Riley
      Ruvalcaba (BRR) syndrome. The BRR syndrome is a rare disorder which presents most
      commonly in childhood. Cowden disease is a disease of adulthood and is
      inadequately described in children. Because of the considerable phenotypic
      overlap between the two disorders, and the cytogenetic and molecular findings in
      our patient, we suggest that BRR syndrome and Cowden disease are allelic.

PMID- 9286464
TI  - Comparison of plasma lipids and vitamin E in young and middle-aged subjects on
      potato crisps fried in palmolein and highly oleic sunflower oil.
AB  - We previously found no difference in healthy young adults' plasma cholesterols
      between palmolein and olive oil as the major dietary lipid, although the former
      is high in palmitic acid (16:0) but the latter in oleic acid (18:1 cis). In the
      experiment reported here we compared the effects of palmolein against another
      monounsaturated oil, highly oleic sunflower oil (HOSO), on plasma cholesterol in
      both young and middle-aged healthy adults. The test oils were provided as frying
      oil of potato crisps (150 g/day in men; 100 g/day in women) against low-fat
      background diets in free-living motivated volunteers. The design was a randomised
      double-blind 4-week/3-week crossover trial. Compliance was monitored with
      continuous dietary diaries and by measuring (fasting) plasma lipid fatty-acid
      pattern. Plasma lipids and vitamin-E compounds were measured at the start and
      twice at the end of each test period. In combined young plus older subjects (n =
      42) mean plasma total and low-density-lipoprotein cholesterol (LDL-c) values were
      both 7% (significantly) lower on HOSO than on palmolein, but because high-density
      lipoprotein cholesterol (HDL-c) was also 5% lower, the LDL-c/HDL-c ratio was only
      3% lower on HOSO than on palmolein. The difference between the present results
      with HOSO and previous results with olive oil both compared against palmolein
      suggest that olive oil is associated with higher plasma cholesterols than other
      monounsaturated oils. In both the young and older subgroup, LDL-c was lower on
      HOSO but because HDL-c moved down too in the young subgroup, the LDL-c/HDL-c
      ratio was lower on HOSO only in the older subjects. Palmolein has an unusual
      pattern of E vitamins, with a high content of tocotrienols, notably the gamma
      isomer. Unlike alpha-tocopherol however, there was no sign of these tocotrienols
      in subjects' plasmas.

PMID- 9286466
TI  - Effects of malnutrition and atherosclerosis on the fatty acid composition of
      plasma phospholipids in the elderly.
AB  - The fatty acid profiles of plasma phospholipids have been compared in 53 elderly
      subjects suffering from malnutrition (group U, 17 subjects) or from
      atherosclerosis (group A, 15 subjects). A control group was also included in the
      study (group C, 21 subjects). Main differences were observed in
      phosphatidylcholine (PC). In group U, the proportion of monounsaturated fatty
      acids increased in PC, which was reflected by an increase in unsaturated fatty
      acids without significant modification of essential fatty acids. In group A, no
      major modification has been observed statistically, although the proportion of
      saturated fatty acids tended to increase.

PMID- 9286465
TI  - Low-density lipoprotein ability to generate lipoperoxides in healthy subjects:
      variations according to age.
AB  - Oxidized low-density lipoproteins (LDLs) are recognized to be involved in
      atherosclerosis development. Since the plasma oxidized LDL assay is inadequate
      because of the short half-lives of LDLs, measurement of the in vitro ability of
      LDLs to generate lipoperoxides (LDL-GLs) has been preferred. The present study
      displays a profile of LDL-GLs in a group of 175 healthy subjects, using a method
      to measure thiobarbituric acid-reactive substances. We have observed an increased
      LDL-GL level according to age.

PMID- 9286468
TI  - Turnover of short-lived proteins in chick leukocytes following dietary
      treatments.
AB  - The effect of protein intake (10 vs. 20%) on synthesis and degradation of short
      lived leukocyte proteins in vitro was shown in 21-day-old chicks. Protein
      synthesis was measured for 1 or 2 h and protein degradation for 1.5 or 4 h
      following an 8-day dietary treatment. Leukocyte proteins were fractionated on a
      slab gel into 11 or 100 fractions, and the imaging radioactivity was calculated
      for protein synthesis and degradation. The degradation rates in most of the
      protein fractions were higher in the leukocytes of chicks fed 20% dietary protein
      than in those fed 10% protein. Protein fractions of M(r) approximately 25-37 kD
      exhibited the most marked differences between the two dietary treatments. This
      technique of measuring turnover rates of short-lived proteins in leukocytes could
      potentially be used to examine the effect of nutritional treatments in animals
      and man as well as to check the effect of catabolic conditions in humans on
      protein turnover.

PMID- 9286467
TI  - Comparison of the effects of two weeks' intervention with different meal
      frequencies on glucose metabolism, insulin sensitivity and lipid levels in non
      insulin-dependent diabetic patients.
AB  - AIMS: To compare the effects of 2 weeks on different meal frequencies on glucose
      metabolism, lipid levels and 24-hour blood pressure in non-insulin-dependent
      diabetic subjects. METHODS: Ten non-insulin-dependent diabetic outpatients from
      Aarhus City participated in a crossover study design. None were treated with
      insulin. The patients were randomly allocated to two isoenergetic diets either
      taken as three or eight meals per day for 2 weeks each. At the end of each
      period, the diurnal blood pressure and the responses to a test meal were
      measured. Furthermore, a hyperinsulinemic, euglycemic clamp was placed. RESULTS:
      Both the insulin sensitivity and 24-hour ambulatory blood pressure were similar
      as were the responses of glucose, insulin and free fatty acids to a carbohydrate
      rich test meal at the end of the two diet periods. The HDL-cholesterol level was
      lowest in response to the 8-meal diet (p = 0.02). CONCLUSION: Increasing meal
      frequencies in a 2-week treatment period with weight-maintaining diets on an
      outpatient basis subdued the HDL-cholesterol levels but apparently had no impact
      on glucose metabolism or diurnal blood pressure in NIDDM subjects. These results
      give no indications of long-term beneficial effects of increasing the meal
      frequency in NIDDM patients.

PMID- 9286469
TI  - Effects of arsenic (V)-chromium (III) interaction on plasma glucose and
      cholesterol levels in growing rats.
AB  - Recent studies have demonstrated interaction between arsenic (As) and chromium
      (Cr) affecting absorption and/or protein catabolism. In the present study the
      possible effects of As(V)/Cr(III) interaction on growth rate, organ weight, and
      the two main organic functions of Cr, i.e., regulation of plasma glucose levels
      and total plasma cholesterol levels, was examined in weaned male Wistar rats. The
      diet of 20 rats was supplemented with 5 micrograms of As(V) and/or Cr(III) per
      gram of food for 10 weeks. As/Cr interaction did not significantly affect growth
      rates on organ weight:body weight ratios but did decrease total plasma
      cholesterol levels, though the decrease was not as pronounced as in the group
      supplemented with Cr alone (p < 0.1). Since supplementation with As(V) produced
      the opposite effect (96.83 vs. 47.27) (p < 0.01), the combined use of As and Cr
      may prove beneficial in cases of chronic As(V) intoxication. Supplementation
      treatment with As(V) and Cr(III) combined had no significant effect on glucose
      levels, because though As(V) affects Cr tissue levels and thus alters the effect
      of Cr on plasma cholesterol levels, individual effects of As(V) and Cr(III) are
      similar, and hence basal glucose levels are unaffected.

PMID- 9286471
TI  - Is the incidence of cancer increased in patients with Crohn's disease or after
      its complications or treatment?

PMID- 9286470
TI  - Effect of tea decoction given to rats ad libitum for a relatively long time on
      body weight gains and iron, copper, zinc, magnesium concentrations in blood,
      liver, duodenum and spleen.
AB  - The aim of our study was to examine the influence of tea decoction given ad
      libitum for 15 days on body weight gains and on nonheme iron, copper, zinc and
      magnesium concentrations in the blood from a semisynthetic diet provided to
      healthy rats. We have also evaluated the reserves of these essential minerals in
      the liver, duodenum and spleen. Our findings indicate that the tea decoction
      significantly reduced the total body weight growth in the tea group as compared
      to the control group (p < 0.0001). The total body weight gains for the control
      and tea groups were 13.2 and 2.4%, respectively. On the other hand, our data show
      that the tea decoction significantly reduced nonheme iron concentration in the
      total blood by 31.8% (p < 0.001). Similarly, the reserve of iron stored in the
      liver and the duodenum declined more significantly by 57% (p < 1.10(-7) and 50.5%
      (p < 1.10(-6)). respectively. In contrast to the inhibitory effect on iron
      concentration and its stored reserve, tea decoction significantly increased zinc,
      copper and magnesium concentrations in the total blood. Zinc, copper and
      magnesium concentrations increased by 29.4 (p < 0.05), 69.0 (p < 0.001) and 48.7%
      (p < 0.001), respectively. Moreover, tea decoction treatment did not raise the
      reserve of zinc or copper significantly but it increased the reserve of magnesium
      stored in the liver (p < 0.05).

PMID- 9286472
TI  - Glucocorticoid therapy. The Canadian Association of Gastroenterology Practice
      Affairs Committee.

PMID- 9286474
TI  - Management of viral hepatitis: clinical and public health perspectives--a
      consensus statement. CASL Hepatitis Consensus Group. Canadian Association for
      Study of the Liver.

PMID- 9286473
TI  - Multifocal gastric neoplasia after recurrent laser therapy for the watermelon
      stomach.
AB  - Repeated laser therapy has become an accepted therapeutic approach in the
      treatment of watermelon stomach, and to date no important negative sequelae have
      been reported. The case of a patient who underwent repeated sessions of
      neodymium: yttrium aluminum garnet (Nd:YAG) laser therapy over a five-year period
      for the treatment of the watermelon stomach is presented. Postlaser therapy the
      patient developed deep ulcerations that would heal; however, he ultimately
      developed a nodular antrum. Random biopsies of antral nodules revealed carcinoma
      in-situ. A Billroth I gastrectomy revealed two foci of carcinoma-in-situ/high
      grade dysplasia and multiple foci of lower grades of dysplasia. This case
      suggests a possible association between use of laser therapy and development of
      gastric neoplasia.

PMID- 9286476
TI  - Hereditary colon cancer.
AB  - Hereditary colon cancer comprises approximately 10% of total colon cancer, a
      disease that affects 6% of the North American population. Knowledge of molecular
      genetics of familial adenomatous polyposis and hereditary nonpolyposis colon
      cancer has improved our diagnostic abilities and management, as well as furthered
      our understanding of the mechanisms of tumour initiation and progression.

PMID- 9286477
TI  - Practice guidelines: why do we need them?

PMID- 9286475
TI  - Perinuclear antineutrophil cytoplasmic antibodies in collagenous or lymphocytic
      colitis with or without celiac disease.
AB  - Microscopic forms of colitis, including lymphocytic and collagenous colitis, have
      been observed in both those with and without celiac disease. Although perinuclear
      antineutrophil cytoplasmic antibodies (p-ANCA) occur in most patients with
      ulcerative colitis, investigations in microscopic, particularly lymphocytic,
      colitis are still needed. In this study atypical p-ANCA was evaluated in 55
      patients, including 27 with celiac disease alone, 13 with celiac disease and
      concomitant lymphocytic colitis, and 15 with microscopic forms of colitis,
      including lymphocytic and collagenous colitis. Nine patients (16.3%) had atypical
      p-ANCA, including six with celiac disease and three with a microscopic form of
      colitis alone. Although five of the six positive celiac disease patients had
      lymphocytic colitis, all three celiac disease patients with associated primary
      sclerosing cholangitis--a separate risk factor for a positive assay result--were
      serologically positive for atypical p-ANCA. These results indicate for the first
      time that this serological marker may occur in histologically defined celiac
      disease with or without concomitant lymphocytic colitis. Furthermore, these
      results suggest that the pathogenesis of ulcerative colitis differs from that of
      lymphocytic colitis and further emphasizes the heterogeneous nature of these
      newly recognized types of colonic inflammatory mucosal disorders.

PMID- 9286478
TI  - Canadian Association of Gastroenterology Practice Guideline for granting of
      privileges to perform gastrointestinal endoscopy.

PMID- 9286479
TI  - High prevalence of serum immunoglobulin G antibody to Helicobacter pylori and
      raised serum gastrin and pepsinogen levels in enlarged fold gastritis.
AB  - To clarify the prevalence of Helicobacter pylori infection in enlarged fold
      gastritis, serum immunoglobulin (Ig) G antibody to H pylori was determined in 19
      patients with severely enlarged gastric body folds (the widest fold greater than
      10 mm on the radiograph), 55 patients with moderately enlarged folds (6 to 10 mm)
      and 44 control subjects (5 mm or less). The prevalence of serum IgG antibody to H
      pylori in the severe (100%) and moderate groups (100%) was significantly higher
      than that in controls (34.1%) (P < 0.01). There were significant differences
      among the three groups in serum gastrin, pepsinogen I and pepsinogen II levels
      (severe had the highest levels, followed by moderate and then controls, P <
      0.001). H pylori colonization in the gastric mucosa was confirmed by culture,
      urease test or both, and inflammation by hematoxylin and eosin stain in the 25 H
      pylori seropositive patients who underwent endoscopy and biopsy. Results suggest
      that H pylori infection is highly prevalent in enlarged fold gastritis. Further
      studies on enlarged fold gastritis and H pylori infection are needed.

PMID- 9286481
TI  - Occult liver abscess following clinically unsuspected ingestion of foreign
      bodies.
AB  - Two uncommon cases of foreign body (a wooden clothespin and a toothpick)
      perforation of the gur with associated pyogenic liver abscesses are presented.
      These cases illustrate the difficulties of preoperative diagnosis. The lack of
      history of ingestion of foreign bodies, variable clinical presentation of the
      conditions and radiolucent natures of the foreign bodies all play a role in
      impeding the diagnosis preoperatively. This report emphasizes the role of
      ultrasound and computed tomographic scan in evaluating similar cases. Any patient
      with known risk factors for ingestion of foreign body should arouse suspicion and
      be investigated further.

PMID- 9286480
TI  - Evaluation of salivary antibodies to detect infection with Helicobacter pylori.
AB  - Helicobacter pylori infection is an important cause of peptic ulcer disease and
      chronic gastritis. Infection with this bacterium stimulates the production of
      immunoglobulin (Ig) G antibody. Salivary IgG antibody tests to detect H pylori
      infection offer a convenient and noninvasive method of diagnosis. To evaluate an
      IgG salivary antibody kit, saliva was collected from 157 out-patients with
      dyspepsia referred for endoscopy to a tertiary centre. A salivary IgG ELISA
      antibody assay was performed using the Helisal Helicobacter pylori (IgG) assay
      kit, and at least four gastric biopsies were obtained. H pylori infection was
      confirmed by demonstration of the organism on Warthin-Starry silver stain
      (sensitivity 85%, specificity 55%). The prevalence of infection with H pylori was
      30%. When the analysis was redone, excluding those treated with eradication
      therapy, the results were similar (sensitivity 86%, specificity 58%). The
      positive predictive value of the assay was 45% and the negative predictive value
      was 90%. Despite the ease of sampling, the assay used has limited diagnostic
      utility, lacking the predictive value to indicate which patients referred with
      dyspeptic symptoms to a tertiary care setting are infected with H pylori.

PMID- 9286482
TI  - Hepatopulmonary syndrome associated with schistosomal liver disease.
AB  - A 55-year-old man with schistosomal liver disease presented with shortness of
      breath, orthodeoxia, platypnea, cyanosis, marked digital clubbing and liver
      failure. Extensive investigation revealed no other etiology for liver disease
      apart from schistosomiases. The diagnosis of hepatopulmonary syndrome was based
      on clinical grounds, as well as abnormal arterial blood gases and positive
      contrast echocardiography. The patient underwent orthotopic liver
      transplantation, which was initially successful, but then died of respiratory
      complications and multi-organ failure on day 42 post-transplantation. To the
      authors' knowledge this is the first report of hepatopulmonary syndrome
      associated with schistosomal liver disease.

PMID- 9286483
TI  - Physiological effects of bulimia nervosa on the gastrointestinal tract.
AB  - Bulimia nervosa is an eating disorder characterized by frequent bouts of binge
      eating accompanied by compensatory behaviour for preventing weight gain
      (purging). It is estimated that 3% to 5% of young women are affected by bulimia
      nervosa, and its prevalence is increasing. Bulimia nervosa afflicts both sexes
      and all races. It can lead to serious medical complications. The expression of
      the disease in the gastrointestinal tract may have a critical role in the
      diagnosis of bulimia nervosa. Physiological effects of bulimia nervosa on the
      gastrointestinal tract include dental caries and enamel erosion; enlargement of
      the parotid gland; esophagitis; changes in gastric capacity and gastric emptying;
      gastric necrosis; and alterations of the intestinal mucosa. Identification of any
      of these factors may aid in establishing an early diagnosis, which has been shown
      to increase the likelihood of recovery.

PMID- 9286484
TI  - Hepatitis B infection and liver transplantation.
AB  - Patients with chronic hepatitis B virus (HBV) infection have historically
      incurred high rates of allograft reinfection from extrahepatic reservoirs of HBV,
      with worse long term outcome compared with that of transplant recipients without
      HBV infection. As a result, chronic HBV infection has been considered a
      contrandication for transplantation. Prophylaxis against HBV recurrence, in the
      form of passive immunization with high dose hepatitis B hyperimmunoglobulin and
      the antiviral agent lamivudine, has recently been demonstrated to decrease the
      risk of reinfection. With appropriate prophylaxis, liver transplantation can be a
      viable proposition for patients with HBV infection. Past experience and current
      status of HBV infection and transplantation are reviewed, with emphasis on the
      issues surrounding prophylaxis.

PMID- 9286485
TI  - Value of peer review of pathology in soft tissue sarcomas.

PMID- 9286486
TI  - Cytogenetics of soft tissue tumors.

PMID- 9286488
TI  - PET imaging in soft tissue sarcomas.

PMID- 9286487
TI  - Molecular genetics of soft tissue sarcomas.

PMID- 9286489
TI  - Metastasectomy for soft tissue sarcomas.

PMID- 9286490
TI  - Post-treatment limb function in soft tissue sarcomas.

PMID- 9286491
TI  - Benign and low-grade tumors of the soft tissues: role for radiation therapy.

PMID- 9286492
TI  - Brachytherapy for soft tissue sarcomas.

PMID- 9286493
TI  - Three-dimensional planning and conformal radiotherapy.

PMID- 9286494
TI  - Radiation-induced bone and soft tissue sarcomas: clinical aspects and molecular
      biology.

PMID- 9286495
TI  - Chemotherapy for metastatic soft tissue sarcomas.

PMID- 9286496
TI  - Adjuvant chemotherapy of soft tissue sarcomas.

PMID- 9286497
TI  - Isolated limb perfusion with high-dose tumor necrosis factor-alpha for locally
      advanced extremity soft tissue sarcomas.

PMID- 9286498
TI  - Soft tissue sarcomas in children.

PMID- 9286499
TI  - Clinical and echocardiographic findings in HIV patients with pericardial
      effusion.
AB  - BACKGROUND AND OBJECTIVES: Pericardial effusion (PE) is frequently found in
      patients infected with the human immunodeficiency virus (HIV), but its clinical
      significance remains unclear. Our purpose was to study the manifestations of HIV
      infected patients with PE and the coexistence of these manifestations with other
      echocardiographic abnormalities, compared with patients without PE. METHODS: We
      reviewed 141 HIV-infected patients in whom echocardiographic study was performed.
      We studied their epidemiological, clinical, hematological, immunological,
      electrocardiographic (ECG) and echocardiographic characteristics and their in
      hospital outcome. RESULTS: Patients with PE (n = 55), compared with those without
      PE (n = 86), were more often clinical stage C and immunological stage 3, had left
      ventricular dysfunction and right-ventricular dilatation more frequently, and had
      been diagnosed as HIV-positive for a longer time. Seven patients with moderate to
      severe PE developed cardiac tamponade. Compared with patients with small PE (n =
      34), those with moderate to large PE (n = 21), had pericardial rub, ECG
      repolarization abnormalities consistent with pericarditis, immunological stage 3,
      left-ventricular dysfunction and right-ventricular dilatation more frequently. In
      3 patients, cardiac tamponade disappeared after anti-tuberculous therapy; in 3
      cases, pericardial drainage was performed (anti-tuberculous therapy was not
      attempted); 1 patient with cardiac tamponade was not drainaged because he was a
      terminal patient with an extensive lymphoma. CONCLUSIONS: PE in HIV-infected
      patients is associated with (1) advanced stages of infection, and (2) left
      ventricular dysfunction and right-ventricular dilatation; (3) presence of
      pericardial rub and ECG alterations consistent with pericarditis suggests the
      existence of moderate to large PE.

PMID- 9286501
TI  - A new cardiology patient simulator.
AB  - We report a new cardiology patient simulator developed through the application of
      new digital computer technology, capable of playing back selected physical
      findings (jugular-venous waves, arterial pulses of carotid, brachial, radial and
      femoral arteries, and cardiac impulses), as well as cardiac sounds, murmurs and
      respiratory sounds that have been prerecorded from actual patients. The examining
      physician uses an ordinary type of stethoscope. Four built-in speakers are
      located in the human-sized mannequin at the classic auscultatory sites (aortic,
      pulmonic, tricuspid and mitral). This compact and portable educational apparatus
      should facilitate medical training in the bedside cardiac examination, of
      physicians, medical students, nurses and paramedics throughout the world.

PMID- 9286500
TI  - Brain natriuretic peptide is a sensitive indicator of impaired left-ventricular
      function in elderly patients with cardiovascular disease.
AB  - We studied the relation between the plasma concentration of brain natriuretic
      peptide (BNP) and echocardiographic findings to determine the sensitivity of BNP
      as an indicator of left-ventricular dysfunction in elderly patients with various
      cardiovascular diseases. The plasma concentration of BNP was positively
      correlated with left-ventricular end-diastolic and end-systolic dimensions (LVEDD
      and LVESD, respectively) and inversely correlated with the left-ventricular
      ejection fraction (LVEF) in patients with prior myocardial infarction, dilated
      cardiomyopathy, and valvular heart disease. The plasma concentration of BNP
      decreased significantly in association with an increase in LVEF and decreases in
      LVEDD and LVESD in patients with congestive heart failure following therapy.
      These observations indicate that the plasma concentration of BNP is a sensitive
      marker of impaired left-ventricular function in elderly patients with various
      cardiovascular diseases and may be useful for evaluating the improvement in left
      ventricular function and the efficacy of therapy in patients with congestive
      heart failure.

PMID- 9286502
TI  - Endothelium-dependent dilation of the coronary arteries in syndrome X: effects of
      the cold pressor test.
AB  - The coronary flow reserve is abnormal in syndrome X, but the response to the cold
      pressor test, which in normals produces flow-mediated endothelium-dependent
      epicardial coronary dilation, has not been studied. In this study, in 12 patients
      with typical syndrome X and angiographically normal coronary arteries, the
      response to the cold pressor test was abnormal with a mean fall in diameter (10
      +/- 8%) in 6 patients, no change in 1, and a minimal increase (4 +/- 2%) in 5
      patients (normal increase 12 +/- 1%). The coronary blood flow fell slightly
      during the cold pressor test, and the coronary vascular resistance increased
      significantly (from 2.4 +/- 1.1 to 3.2 +/- 1.7 mm Hg/cm.s-1.mm2; p = 0.05), both
      abnormal responses. This study confirms that in syndrome X patients there is
      coronary endothelial dysfunction which is apparent in response to physiological
      stimuli induced by the cold pressor test.

PMID- 9286503
TI  - Beta-blockade prevents ventricular failure following aortic regurgitation in
      rabbits.
AB  - This study investigated the effects of chronic beta-blockade on the
      pathophysiology of heart failure following induction of aortic regurgitation
      (AR). Nine rabbits with AR were administered propranolol continuously for 7 days
      (AR+P), 8 rabbits with AR received vehicle for the same period (AR+C), and 7
      rabbits underwent sham operation. Cardiac output was lower and the left
      ventricular end-diastolic pressure was higher in AR+C than in sham-operated
      rabbits, but there was no difference in the right-ventricular end-diastolic
      pressure between the two groups. Down-regulation of beta-adrenoceptors was
      observed in the left ventricle, but not in the right ventricle. All of these
      variables were reversed in AR+P. In left-ventricular failure produced by AR, (1)
      the augmentation of adrenergic drive occurred selectively in the left ventricle,
      and (2) propranolol blunted adrenergic drive and played a protective role against
      myocardial damage.

PMID- 9286505
TI  - Use and limitations of immediate postprocedural intracoronary Doppler blood flow
      measurements for predicting late result after coronary balloon angioplasty.
      Results of a pilot study.
AB  - BACKGROUND AND AIMS: Physiologic measurement of myocardial perfusion in the
      immediate postangioplasty period may complement the angiographic assessment of
      the outcome of the procedure and improve our ability to identify patients at
      increased risk for a suboptimal late result. Immediate in-lab identification of
      patients at risk for late coronary restenosis would allow the interventionalist
      to implement alternate interventional and/or pharmacologic strategies aimed at
      improving the long-term outcome of angioplasty. The present single-center pilot
      study was undertaken to examine prospectively the value of intracoronary Doppler
      flow measurements immediately postangioplasty for predicting long-term patency of
      the dilated coronary artery. PATIENTS AND METHODS: Coronary average peak flow
      velocity (APV) at rest and during hyperemia (6-18 micrograms intracoronary
      adenosine) and coronary flow reserve in the distal coronary segment were measured
      in 24 consecutive patients 10-15 min after successful elective coronary
      angioplasty. Volume flow (Q) was calculated as APV/2 coronary cross-sectional
      area heart rate. Coronary arterial vessels and narrowings were measured by
      quantitative angiography using a geometric based method and automated edge
      detection. The present study reports the findings in the 16 patients undergoing
      conventional balloon angioplasty for whom hard endpoint angiographic data were
      available 4.9 +/- 1.5 months after angioplasty. RESULTS: A linear relation was
      present between angiographically measured minimal luminal dimension immediately
      postangioplasty and the late angiographic result of the procedure (r = 0.71, p =
      0.0005). A greater acute gain during angioplasty was predictive of a larger
      luminal dimension at late angiographic follow-up (p = 0.006). There was no
      relation between the immediate postangioplasty Doppler flow measurements and the
      late angiographic result of the procedure. Late luminal dimension was not related
      to immediate postangioplasty basal or hyperemia APV, nor to immediate
      postangioplasty basal or hyperemic volume flow or to coronary flow reserve (all
      NS). CONCLUSIONS: In this single-center study, intracoronary blood flow and
      Doppler-derived coronary flow reserve immediately postpercutaneous transluminal
      coronary angioplasty were not predictive of long-term vessel patency or late
      coronary restenosis. The immediate angiographic result of angioplasty did
      correlate with the late result of the procedure.

PMID- 9286504
TI  - Endothelium-dependent and endothelium-independent flow regulation in coronary
      vascular regions supplied by arterial and venous bypass grafts.
AB  - The endothelium-dependent and endothelium-independent vasodilation of arterial
      and venous coronary bypass grafts and of epicardial conduit vessels and
      microcirculatory coronary vessels supplied by these grafts was investigated.
      Vasodilatory response and flow regulation were tested with cumulative
      intracoronary doses of acetylcholine (25 and 50 micrograms i.c.), nitroglycerin
      (0.3 mg i.c.), and papaverine (10 mg i.c.) in 10 patients (age 60 +/- 2.3 years)
      with arterial grafts and in 16 patients (age 57.7 +/- 1.5 years) with venous
      grafts. The effect of acetylcholine on arterial and venous bypass grafts and on
      large conduit arteries was evaluated by quantitative coronary angiography.
      Coronary blood flow velocity changes as a parameter of microcirculatory function
      were measured by intraluminal Doppler ultrasound. Indices for coronary flow and
      coronary resistance were calculated from the mean Doppler flow velocity and the
      computed cross-sectional vascular area. The coronary resistance decreased
      endothelium dependent after 25 and 50 micrograms of acetylcholine by 16 +/- 30%
      (p < 0.05 vs. control) and 22 +/- 25% (p < 0.05 vs. control), respectively, in
      regions supplied by venous grafts and by 48 +/- 20% (p < 0.05 vs. control and vs.
      venous graft) and 41 +/- 32% (p < 0.05 vs. control), respectively, in regions
      supplied by arterial grafts. The coronary resistance decreased endothelium
      independent after 0.3 mg nitroglycerin and 10 mg papaverine by 18 +/- 56% (p <
      0.05 vs. control) and 39 +/- 29% (p < 0.05 vs. control), respectively in regions
      supplied by venous grafts and by 45 +/- 45% (p < 0.05 vs. control) and 70 +/- 12%
      (p < 0.05 vs. control and vs. venous graft), respectively in regions supplied by
      arterial grafts. In conclusion, during the long-term course after coronary artery
      bypass grafting, vascular regions supplied by arterial grafts have a better
      preserved endothelium-dependent and endothelium-independent flow reserve as
      compared with vascular regions supplied by venous grafts.

PMID- 9286506
TI  - Prognostic significance of infarction location in patients with recurrent
      myocardial infarction. SPRINT Study Group. Secondary Prevention Reinfarction
      Israel Nifedipine Trial.
AB  - This study assesses the impact of infarct location on immediate (in-hospital) and
      1- and 5-year mortality among patients with reinfarction during the year
      following discharge from the initial episode of myocardial infarction. The
      analysis included 192 patients with a second myocardial infarction who were
      compared in four infarction location groups. The in-hospital mortality associated
      with reinfarction was higher in patients with a second anterior (32%) than with a
      second inferior (18%) location, irrespective of the first infarction location (p
      = 0.03). At 5 years of follow-up, the mortality (65%) tended to be higher in
      patients with a first anterior-second anterior infarction as compared with
      patients with all other combinations of location.

PMID- 9286507
TI  - QRS prolongation measured by a new computerized method: a sensitive marker for
      detecting exercise-induced ischemia.
AB  - This study compared thallium stress testing and exercise changes in QRS duration
      using a computerized 'optic scanner' in three groups. Group 1 consisted of 108
      subjects with positive exercise ECG tests by ST-T segment criteria and with
      proven coronary artery disease. Group 2 included 19 subjects with nondiagnostic
      exercise ECG ST-T changes and with proven coronary artery disease. Group 3 was
      formed by 38 healthy controls. Group 1: Mean increase in exercise QRS width of
      12.4 +/- 14 ms. Group 3: Mean decrease in exercise QRS width of 4.9 +/- 9.3 ms (p
      < 0.0001). Group 2: Mean QRS prolongation of 7.8 +/- 9.2 ms, which was
      significantly different from the controls (p < 0.0001) but not from group 1. When
      compared to thallium stress testing, exercise QRS prolongation had a sensitivity
      of 93%, specificity of 71%, relative risk of 5, and positive predictive value of
      86%. QRS duration measurement can improve the diagnostic accuracy of the exercise
      ECG stress test.

PMID- 9286509
TI  - Can ECG changes predict the long-term outcome in patients admitted to hospital
      for suspected acute myocardial infarction?
AB  - 7,028 patients with suspected acute myocardial infarction and discharged alive
      from hospital were followed in a 10-year community-based study. The long-term
      prognosis was relatively good if the electrocardiograms (ECGs) were normal (5
      year all-cause death rate 5%), poor with uncodable ECGs showing rhythm or
      conduction disturbances (37%), and intermediate with new Q wave, new ST
      elevation, new T wave inversion or ischemic ECG (17-21%), and with new ST
      depression (27%). Similar patterns were found for ischemic cardiac death and
      reinfarction. The long-term prognosis of patients with suspected acute myocardial
      infarction is relatively good if the ECGs are normal and poor if ECGs are
      uncodable. ST depression may be a marker for a worse long-term outcome.

PMID- 9286508
TI  - Exercise testing in patients with chest pain and normal coronary arteries:
      improving test specificity by use of a simple logistic model.
AB  - Despite an exercise electrocardiogram (ECG) positive for ischemia by established
      criteria, many patients referred for coronary angiography to evaluate chest pain
      are found to have angiographically normal coronary arteries (NCA). Exercise ECG
      were analyzed from 27 patients with chest pain and angiographically NCA and 28
      patients with chest pain and coronary artery disease (CAD) using univariate and
      multivariate logistic regression analysis. We derived the following logistic
      model for the logit probability of CAD: 3 + SEX x 4 - METs x 0.7 + STDV5 x 0.8,
      where SEX = 0 for female and SEX = 1 for male, METs = maximal estimated work load
      (metabolic equivalents) and STDV5 = horizontal or downsloping ST depression (mm)
      in V5. A logit probability > or = 0 identified CAD with a sensitivity of 79% and
      a specificity of 89%. The model correctly identified 28/36 (78%) patients with
      CAD, and 7/10 (70%) patients with NCA (correct diagnosis 76%; p < 0.02) in a
      separate random group of 46 unselected patients with positive exercise tests
      undergoing diagnostic coronary angiography.

PMID- 9286510
TI  - Exercise training in mild hypertension: effects on blood pressure, left
      ventricular mass and coagulation factor VII and fibrinogen.
AB  - The aim of this study was to assess the effects of aerobic exercise on resting
      and 24-hour blood pressure (BP), left ventricular mass (LVM), plasma fibrinogen
      and factor VII (FVII). For this purpose 14 sedentary subjects with untreated
      diastolic BP between 90 and 104 mm Hg completed a 12-week supervised exercise
      program. At the end of this period, 8 subjects resumed a sedentary life-style and
      were reexamined 2 months later (detraining). Baseline, posttraining and
      postdetraining examinations included resting BP assessment, ambulatory BP
      monitoring, cardiopulmonary stress test, echocardiography and measurements of
      plasma fibrinogen and FVII. Exercise-mediated increase in aerobic fitness (VO2
      max + 24%) was associated with a significant reduction in resting systolic and
      diastolic BP (p < 0.01), mean systolic and diastolic 24-hour BP (p < 0.001) and
      LVM index. As for the coagulation parameters only the concentration of fibrinogen
      significantly decreased (p < 0.01) whereas FVII remained unchanged. The 8
      subjects that resumed a sedentary life-style were reexamined 2 months later:
      their resting BP, 24-hour BP and fibrinogen concentration returned to baseline
      values; only the effect on LVM was conserved. Our study underlines the usefulness
      and safety of regular physical exercise in mild hypertension. Most of the
      patients (11 of 14) had their BP normalized and a significant reduction in LVM
      and fibrinogen concentration was observed, leading to an overall improvement in
      coronary risk profile.

PMID- 9286511
TI  - Paroxysmal atrial tachycardia with second-degree atrioventricular block.
AB  - Paroxysmal atrial tachycardia with atrioventricular block usually indicates
      potentially dangerous overdigitalization, and serious heart disease is almost
      universally present. In this report, we describe a patient with a structurally
      normal heart who manifested spontaneously intra-atrial reentrant tachycardia with
      Wenckebach atrioventricular block in the absence of medications. In this patient,
      the longest atrial paced cycle length that induced atrioventricular nodal block
      was 390 ms, and the atrial cycle length during tachycardia ranged from 360 to 400
      ms. The electrophysiologic study in our patient demonstrated that second-degree
      atrioventricular block during atrial tachycardia may occur in patients without
      structural heart diseases or taking any medication.

PMID- 9286512
TI  - Electromechanical dissociation following verapamil and propranolol ingestion: a
      physiologic profile.
AB  - We present a case of combined verapamil and propranolol ingestion in a young
      woman with a DDD pacer from whom hemodynamic, echocardiographic, and toxicologic
      data were obtained simultaneously. Analysis of the data from these combined
      sources suggests a progression of (1) recovery of myocardial contractility, (2)
      return of systemic vascular resistance, and (3) return of intrinsic electrical
      activity of the heart. That contractility returns before intrinsic electrical
      activity strongly for the early use of transvenous temporary pacing wires.
      Furthermore, our patient's complete recovery after a prolonged electromechanical
      dissociation arrest would again argue for very aggressive resuscitation efforts
      in this setting.

PMID- 9286514
TI  - A man in the thunderstorm: coronary injuries and electric shock.

PMID- 9286513
TI  - Rescue PTCA for a totally occluded left main coronary artery in acute myocardial
      infarction with cardiogenic shock: technical success and long-term survival.
AB  - Percutaneous transluminal coronary angioplasty was performed after failed
      thrombolysis in a 54-year-old man for total occlusion of the left main coronary
      artery in the setting of acute myocardial infarction with cardiogenic shock. The
      procedure was successful in terms of vessel recanalization and restoration of
      flow. The recovery of muscle function was limited due to the time lag between
      onset of symptoms and recanalization. This case highlights the crucial role of
      early identification and prompt referral of patients with extensive ischemia to
      centers with the capability for emergency percutaneous revascularization
      procedures.

PMID- 9286515
TI  - Prediction of the extent of caries in pit and fissure lesions in a field trial in
      the west of Scotland.
AB  - A field trial is in progress in which 14 community clinical dental officers and
      19 general dental practitioners were asked to record the actual extent of fissure
      lesions and how this compared with the cavity size they expected. Participating
      operators worked under their normal conditions of daily practice. Forty-eight to
      fifty-seven percent of 644 prepared cavities were of the expected size upon
      investigation, depending on the diagnostic technique used. Greater accuracy was
      achieved among the smaller cavities (58-75% as expected) than with the larger (52
      69% larger than expected). More difficulty with cavity size prediction occurred
      with the lower right first molar than with the other first molar teeth and with
      both mandibular second molars compared to the maxillary molars. Comparisons
      between the accuracy of cavity size prediction achieved using a visual inspection
      in combination with the probe and a visual inspection alone showed no significant
      difference. Under the conditions of this field trial, considerable difficulties
      were experienced in predicting cavity size accurately.

PMID- 9286516
TI  - Structural analyses of plaque and caries in relation to the morphology of the
      groove-fossa system on erupting mandibular third molars.
AB  - Using 22 erupting human third mandibular molars, this study investigated: (1) the
      relationship between the morphology of the interlobal groove and the histological
      features of caries, (2) the ultrastructural features of the interlobal groove
      contents, and (3) whether the morphology of interlobal grooves influences the
      viability of the microorganisms. Posteruption time was classified as (1) < 3
      months (7 teeth), (2) 3-12 months (8 teeth) and (3) > 12 months but < 18 months
      (7 teeth). The teeth were pre- and postfixed, and buccolingual sections were
      prepared. The mesial/distal interlobal groove on 116 sections was classified as
      fissure-like or groove-like. All sections were embedded and ground, and
      microradiographs were made. The interlobal groove contents were analyzed on two
      sections from each tooth, one with a fissure-like and one with a groove-like
      morphology, giving a total of 44 sections. Eighteen teeth (82%) had evidence of
      caries. Severity of caries was associated with length of posteruption time.
      'Fissures' were not more prone to caries than 'grooves'. In about 70% of the
      'fissures' caries had penetrated deepest at the entrance rather than in the
      deeper parts. LM and TEM examinations from 1 tooth disclosed erythrocytes, enamel
      organ cells and pioneers of microorganisms in the interlobal grooves. All other
      interlobal grooves were occupied by microorganisms, mainly gram-positive coccoids
      and small rods. Viable microorganisms were seen at the entrance as well as at the
      bottom part of the 'grooves'. In 'fissures' viable microorganisms were primarily
      observed at the entrance, while in deeper parts the microorganisms were less
      viable or dead. A moderate association was observed between the viability of the
      microorganisms and differences in the depths of caries penetration in the
      fissures. Thus, the internal morphology of the interlobal grooves influenced the
      conditions for bacterial growth and this determined the location for caries
      progression within the groove-fossa system.

PMID- 9286517
TI  - Bacterial colonization of mineralized and completely demineralized dentine in
      situ.
AB  - The changing environment in a developing root lesion may result in a succession
      of the microbial flora in the dentine. As demineralization proceeds, the
      collagenous matrix is exposed, which could be conducive to the growth of specific
      microorganisms. In this study both sound and completely demineralized dentine
      were placed together in the partial prothesis of 8 individuals to test whether
      the type of substrate influenced the composition of the bacterial flora. After 6
      weeks the degradation of the collagenous matrix, the demineralization of the
      dentine and the microbial composition were assessed. The collagen loss varied
      between 0 and 69 wt%. Mineral loss from the originally sound dentine specimens
      ranged from virtually none to complete demineralization. Percentages of total
      streptococci, mutans streptococci, Actinomyces and lactobacilli isolated from
      both dentinal substrates did not differ significantly. The percentage of
      lactobacilli in the dentine specimens was positively correlated to the lesion
      depth. The percentage of Actinomyces species was significantly higher in both the
      dentine specimens that had been demineralized in vitro and those that were found
      to be completely demineralized in situ compared to the partially demineralized
      dentine specimens. In vitro, no collagenolytic activity of the predominant flora
      isolated from both dentinal substrates could be shown.

PMID- 9286518
TI  - In situ relationship between sucrose exposure and the composition of dental
      plaque.
AB  - The aim of this study was to analyze the composition of dental plaque according
      to sucrose exposure. Twelve adult volunteers took part in this crossover study
      done in four phases of 28 days each. For each phase of the study, an acrylic
      resin appliance containing four human dental enamel blocks was constructed for
      each volunteer. A 20% sucrose solution was dripped onto the enamel blocks from 0
      to 8 times/day. The volunteers were randomly assigned to the treatments. During
      the experimental period all the subjects used fluoride-free dentifrice, refrained
      from brushing the enamel blocks and drank water fluoridated at 0.70 ppm F. After
      each phase the concentrations of fluoride (F), calcium (Ca), phosphorus (P) and
      total carbohydrate were determined in dental plaque. Statistical analyses showed
      that frequent sucrose exposure significantly (p < 0.05) reduced the F, Ca and P
      concentrations in dental plaque, but increased the alkali-soluble carbohydrate
      concentration. The results suggest that the cariogenicity of dental plaque formed
      in the presence of sucrose cannot be attributed only to its higher porosity, but
      the lower inorganic concentration may also be important.

PMID- 9286519
TI  - Efficacy of a chlorhexidine and a chlorhexidine-fluoride varnish mixture to
      decrease interdental levels of mutans streptococci.
AB  - The aim of the present study was to evaluate and compare the efficacy of a
      chlorhexidine/thymol-containing (CHX) and a chlorhexidine/thymol/fluoride
      containing (CHX + F) varnish to decrease interdental levels of mutans
      streptococci (MS). Eighty-two healthy schoolchildren (11-13 years) with high
      scores of salivary MS were selected by a screening procedure and randomised into
      two groups. MS were enumerated at all mesial interdental sites of the first
      permanent molars with the aid of a modified chair-side technique. The interdental
      molar and premolar sites were treated with either a 1% CHX varnish (Cervitec) or
      a 1:1 mixture of the CHX varnish and a fluoride varnish containing 0.1% w/w
      difluorsilane (Fluor Protector; CHX + F) on two occasions within a 2-week period.
      The varnishes were applied with a small brush after cleaning with dental floss
      and drying with air. Follow-up samples from the interdental areas were collected
      after 1 and 3 months. Both groups exhibited a similar statistically significant
      (p < 0.05) reduction of interdental MS after 1 month when compared with baseline.
      After 3 months, a significant reduction (p < 0.05) was still found in the CHX + F
      varnish group but not in the CHX varnish group. In conclusion, the results
      suggest that the addition of fluoride to an antibacterial varnish might improve
      the long-term efficacy in diminishing the cariogenic microbial challenge. Thus,
      the mixed varnish concept should be further developed and warrants an
      implementation of clinical studies.

PMID- 9286520
TI  - Salivary fluoride concentration and plaque pH after using a fluoride-containing
      chewing gum.
AB  - The aim was to study the salivary fluoride (F) concentration and plaque pH
      recovery on the chewing and the non-chewing side of the dentition during and
      after chewing 1 piece of chewing gum containing 0.25 mg F as NaF. Ten subjects
      refrained from toothbrushing for 3 days. On the fourth day, they rinsed for 1 min
      with 10 ml of a 10% sucrose solution. When plaque pH had reached a low value,
      they started to chew for either 5, 10, 15, 20, 30 or 45 min. Measurements of F
      concentration in saliva and of pH of approximal plaque were carried out at 2
      contralateral sites for up to 60 min. In each individual, the chewing and non
      chewing side were registered. Two to 3 times higher salivary F concentrations
      (expressed as area under the curve, AUC) were found on the chewing than on the
      non-chewing side (p < 0.05 or p < 0.01). The most pronounced recovery of plaque
      pH after the sucrose rinse was also registered for the chewing side, but the
      difference between the chewing and the non-chewing side was not so obvious as for
      the salivary F concentration. Significantly higher values of plaque pH (expressed
      as AUC) were found during prolonged chewing (p < 0.05 or p < 0.01), while only
      small numerical differences in salivary F concentration were noted between short
      and long chewing times. Thus, this study showed: (1) that the F concentrations in
      saliva after chewing a F-containing chewing gum were highest on the chewing side,
      and (2) that a prolonged chewing time increased the plaque pH recovery after a
      sucrose rinse, but had only a minor effect on the salivary F concentration.

PMID- 9286521
TI  - Effect of low levels of fluoride on proton excretion and intracellular pH in
      glycolysing streptococcal cells under strictly anaerobic conditions.
AB  - The effect of low levels of fluoride on intracellular acid production and proton
      excretion in Streptococcus mutans NCTC 10449 at different growth and
      extracellular pH (pHo) levels was monitored under strictly anaerobic conditions.
      The sensitivity of S. mutans to fluoride increased as pHo decreased. Cells grown
      under acidic (pH 6.0 and 5.5) conditions were more resistant to fluoride than
      cells grown at a neutral pH. Under acidic extracellular conditions (pHo = 5.0),
      0.025 mM fluoride inhibited proton excretion by approximately 50% in cells grown
      at pH 7.0. Slightly higher levels of fluoride (0.05-0.07 mM) were required for
      50% or more inhibition in cells exposed to alkaline extracellular conditions or
      cells grown at acidic pH. Such levels of fluoride are about 10-20 times lower
      than that reported previously. Therefore, it is possible that as pH falls during
      initial bacterial glycolysis, sufficient amounts of anionic fluoride may be
      released, from its bound form in plaque, to cause significant inhibition of net
      proton movement out of the bacterial cell during further glycolysis, especially
      under the anaerobic environment of the deep layers of plaque. In addition to
      proton excretion, fluoride was also found to inhibit intracellular acid
      production.

PMID- 9286522
TI  - Fluoride and mutans streptococci levels in plaque on aged restorations of resin
      modified glass ionomer cement, compomer and resin composite.
AB  - The use of fluoride-releasing restoratives such as glass ionomer cements (GICs)
      has increased during the last decade. The antibacterial effect of released
      fluoride is thought to be a possible caries-preventive effect of these
      restorations. In this study fluoride concentrations in plaque on 1-year old resin
      modified GIC, compomer and resin composite restorations were compared
      intraindividually and related to the occurrence of caries-associated bacteria.
      Plaque from class III restorations of the three restorative materials and from a
      proximal enamel surface in 18 individuals was analysed. Low fluoride levels were
      detected in all the samples, while the resin-modified GIC samples showed
      significantly higher amounts. The distribution of oral streptococci, mutans
      streptococci and lactobacilli did not differ significantly among the surfaces and
      did not correlate to the fluoride levels in the samples. A good correlation was
      found between the counts of mutans streptococci in saliva and their proportions
      in the plaque. The results indicate that the fluoride concentrations released in
      vivo from 1-year-old restoratives are not high enough to affect the plaque levels
      of the caries-associated bacteria mutans streptococci and lactobacilli.

PMID- 9286523
TI  - In vivo cariostatic effect of resin modified glass ionomer cement and amalgam on
      dentine.
AB  - Fluoride-releasing materials have been reported to be bactericidal in vitro. This
      may be of benefit to modern dentistry, which is directed to the preservation of
      tooth tissue during restorative treatment. Little is known about in vivo effects.
      The aim is to investigate the influence of a resin-modified glass ionomer cement
      (RM-GIC) on carious dentine that remains under restorations, compared to amalgam.
      Using a split month design, 40 molar pairs in 40 patients (mean age 14.9 years)
      were selected, based on clinically and radiographically diagnosed occlusal
      dentine caries. Under aseptic conditions, the enamel was removed and the carious
      dentine was sampled just beneath the dentino-enamel junction using a round bur.
      Without further removal of carious dentine, the molars of a pair were alternately
      restored with RM-GIC or amalgam. The colour and the consistency of the carious
      dentine were assessed. The samples were processed for microbiological
      determination of total viable counts (TVC), mutans streptococci (MS), and
      lactobacilli (LB). After 6 months the molars were reopened, similarly sampled and
      evaluated, and then permanently restored after complete caries removal. For both
      materials a substantial decrease in the numbers of TVC, MS and LB was found after
      the 6-month period. Also a positive effect was observed on the colour and the
      consistency of the remaining carious dentine, which was comparable for the two
      materials. RM-GIC showed a significantly larger decrease in counts of MS and LB
      than amalgam, but not for TVC. Since in only few cavities the number of bacteria
      decreased under the level of detection, it is still considered essential to
      remove all carious dentine during restorative treatment.

PMID- 9286524
TI  - The cessation of fluoridated water administration and the fluoride distribution
      profiles in rat molar cementum.
AB  - The aim of this work was to obtain further information about the origin of
      fluoride profiles in cementum. Fluoride was administered to rats at varying doses
      (0.50, 100 ppm F in drinking water) and for different durations (4, 13 and 25
      weeks). Fluoride distribution across the full thickness of molar cementum in rats
      was measured by means of an abrasive micro-sampling technique. The average
      fluoride concentrations in cementum increased significantly with increasing dose
      and duration of fluoride administration. The relative reduction of the average
      fluoride concentrations after cessation of fluoride administration was 94.2-36.5%
      at 50 ppm F and 62.2-49.2% at 100 ppm F in the outer layers (1-60 microns) and
      91.5-24.1% at 50 ppm F and 74.1-7.6% at 100 ppm F in the middle (61-120 microns)
      layers of the cementum, respectively. The reduction rates were more closely
      related to the time intervals following cessation rather than fluoride
      concentrations in drinking water or specificity within the cementum. Two factors
      which may influence this are new cementum formation after withdrawal of fluoride
      and some fluoride release from cementum surfaces when the fluoride supply
      stopped. It was concluded that the cessation of fluoride administration reduced
      the fluoride concentration on the outer layers of cementum differing from bone
      where reduction occurs across the entire thickness.

PMID- 9286525
TI  - Transformation of hydroxyapatite to fluorapatite by irradiation with high-energy
      CO2 laser.
AB  - High-energy laser irradiation has been shown to cause crystalline transformations
      in apatites, which may lead to the formation of tricalcium phosphates with a
      resulting decrease in acid resistance. Depending on the nature and energy density
      of laser irradiation used, however, an increase of acid resistance of dental
      enamel has also been reported after laser irradiation. The aim of the present
      study was to investigate the phase transformation of hydroxyapatite (HA) to
      fluorapatite (FA) in a model system that incorporates sodium fluoride (NaF) into
      apatite structure by using laser irradiation. A CO2 laser was used at energy
      densities ranging from 21 to 500 J/cm2. Synthetic HA mixed with NaF (10:1) was
      the target of laser irradiation. The crystalline structures were then
      investigated using X-ray diffraction analysis. The results showed that a phase
      transformation of HA to FA could be realized, and that the threshold energy
      density needed was 38 J/cm2. Not only is the finding crystallographically
      important, but it also opens new perspectives for future research regarding the
      development of laser technology for clinical purposes.

PMID- 9286526
TI  - The fractal structure of caries?

PMID- 9286527
TI  - Intraaortic balloon pump insertion after percutaneous revascularization in
      patients with severe peripheral vascular disease.
AB  - Severe aortoiliac peripheral vascular disease (PVD) is considered a
      contraindication for the placement of an intraaortic balloon pump (IABP) because
      of a high risk of limb ischemia. Recent advances in percutaneous transluminal
      angioplasty (PTA) and stenting have altered the treatment of iliac stenoses such
      that the results of PTA with stenting compare favorably with surgery. We reviewed
      our experience with placement of IABP between July 1994 and February 1996. Of 64
      patients receiving IABP, 17 had known or suspected peripheral vascular disease.
      Severe iliac or distal aortic stenoses were present in 9. These 9 patients
      underwent PTA with or without stenting prior to 10 IABP insertions. Limb ischemia
      occurred in 10% of PVD patients treated with percutaneous revascularization,
      compared to 11% in patients without PVD. No patient had a serious vascular
      complication or required vascular surgery. We conclude that percutaneous
      revascularization in patients with severe aortoiliac PVD, for whom this IABP
      insertion had previously been considered contraindicated, results in a low rate
      of limb ischemia.

PMID- 9286528
TI  - Vascular turf wars: getting a leg up on iliac artery disease during intraaortic
      balloon pumping.

PMID- 9286529
TI  - Early ambulation following 6 French diagnostic left heart catheterization: a
      prospective randomized trial.
AB  - Outpatient cardiac catheterization is frequently performed, but the optimal
      recovery time after sheath removal has not been defined. Left heart
      catheterization was performed via the femoral artery utilizing 6 French catheters
      on 323 outpatients. One hundred thirty-five patients were randomized to ambulate
      at a mean of 2.5 hr (group 1) after puncture site compression, whereas 188
      patients were randomized to ambulate at a mean of 4.1 hr (group 2). Telephone
      follow-up occurred within 48 hr. A small hematoma (< 5 cm) occurred in 2 (1.6%)
      patients in group 1 and in 4 (2.4%) patients in group 2. These results indicate
      that it is safe to ambulate patients 2.5 hr following 6 French diagnostic heart
      catheterization.

PMID- 9286530
TI  - The cath lab bottom line: faster, cheaper, better, safer.

PMID- 9286531
TI  - Pyrogenic reactions in patients undergoing cardiac catheterization associated
      with contaminated glass medicine cups.
AB  - Pyrogenic reactions are potentially life-threatening complications caused by
      bacterial endotoxin. After two cardiac catheterization patients developed rigors
      the same day, the procedures were halted and a case control study was conducted.
      To identify case patients (persons with rigors < or = 3 hr after catheterization
      during September 25-November 9, 1995), we reviewed medical records of all cardiac
      catheterization patients who had a blood culture or received intravenous
      meperidine. Twelve case patients and 40 randomly selected control patients were
      identified. No specific catheter was associated with case patients, but exposure
      to intracoronary-nitroglycerin (NTG) was (odds ratio = 12.0; 95% confidence
      interval 2.2, 75.6). NTG or indocyanine green dye was poured into glass medicine
      cups previously washed in an enzyme cleaner and then sterilized. The cleaner,
      used for an entire day, had elevated levels of gram-negative bacteria (> 10(4)
      colony forming units/mL) and endotoxin (434 endotoxin units [EU]/mL]); the
      reprocessed cups had no live bacteria but had elevated endotoxin levels (median
      2,250 EU). Exposure to contaminated glass medicine cups probably resulted in
      pyrogenic reactions and contributed to death in two critically ill patients.

PMID- 9286532
TI  - Measurement of myocardial fractional flow reserve during coronary angioplasty in
      patients with old myocardial infarction.
AB  - Although myocardial fractional flow reserve (FFRmyo) has been demonstrated to be
      a useful index for determining functional significance of coronary stenosis, the
      data in previous studies was derived from a highly selected group of patients.
      The aim of this study was to investigate the value of FFRmyo in a more clinically
      relevant group of patients, especially in patients who also had resistance vessel
      dysfunction. We measured FFRmyo in 20 consecutive patients who had undergone
      elective coronary angioplasty. FFRmyo was calculated by the ratio of Pc/Pa during
      intracoronary adenosine 5'-triphosphate (ATP; 50 micrograms in the left coronary
      and 20 micrograms in the right coronary artery) induced maximal hyperemia, where
      Pa represents mean aortic pressure obtained by the guiding catheter and Pc
      represents mean distal coronary pressure measured by a 2.1 F infusion catheter.
      In total, 21 vessels were dilated and 14 of them were infarct-related arteries.
      The percent diameter stenosis significantly decreased from 80 +/- 14% to 27 +/-
      17%, and the FFRmyo increased significantly from 0.46 +/- 0.18 to 0.77 +/- 0.15
      after angioplasty. There was no significant differences in the FFRmyo between
      vessels with previous myocardial infarction and those without, after angioplasty
      (0.78 +/- 0.18 vs. 0.76 +/- 0.08). There was a significant correlation between
      the percent diameter stenosis and FFRmyo before (r = 0.83, P < 0.001) and after
      (r = 0.64, P < 0.01) angioplasty. In conclusion, FFRmyo significantly improved
      immediately after angioplasty in vessels with myocardial infarction as well as
      those without. These results led us to suggest the usefulness of FFRmyo in
      patients who had both epicardial stenosis and resistance vessel dysfunction. The
      significant correlation between FFRmyo and quantitative coronary arterial
      diameter stenosis would further support the more widespread use of FFRmyo in the
      clinical setting.

PMID- 9286533
TI  - Is echocardiography or magnetic resonance imaging superior for precoarctation
      angioplasty evaluation?
AB  - We compared the dimensions of the aorta obtained by two-dimensional transthoracic
      echocardiography (echo) (median, 2.5 mo preangioplasty) and magnetic resonance
      imaging (MRI) (median, 4.2 mo preangioplasty) to those obtained by angiography
      (cath) in 13 patients (age, 7.7 +/- 1.6 yr; mean +/- SEM) who underwent
      evaluation for coarctation balloon angioplasty between April 1993-January 1996.
      Echo measurements were obtained from the suprasternal and subcostal sagittal
      planes, MRI measurements from axial and sagittal oblique views, and cath
      measurements from the straight lateral or oblique views. Measurements of the
      diameters of the aortic isthmus, coarctation, descending aorta at the diaphragm,
      and isthmus length were made by all three modalities. Presence of aorto-aortic
      collaterals was determined, and the coarctation length was delineated.
      Investigators were blinded to other measurement data prior to statistical
      analysis. Data analysis by repeated analysis of variance (ANOVA) and Student
      Newman-Keuls testing revealed no statistically significant difference between
      systolic pressure gradient by clinical examination (32.2 +/- 5.9 mm Hg), peak
      instantaneous Doppler evaluation (37.5 +/- 2.9 mm Hg), or preangioplasty systolic
      pressure gradient (32.1 +/- 3.3 mm Hg). With the exception of measurements of the
      descending aorta (echo, 11.7 +/- 0.9 mm vs. MRI, 13.3 +/- 0.8 mm vs. cath, 14.0
      +/- 1.3 mm; P = 0.04), there was no statistically significant difference in
      dimensions of the aortic isthmus (9.2 +/- 0.6 mm vs. 10.5 +/- 0.9 mm vs. 10.8 +/-
      0.9 mm), coarctation site diameter (4.8 +/- 0.6 mm vs. 5.6 +/- 0.9 mm vs. 5.3 +/-
      0.8 mm), or isthmus length (12.4 +/- 2.1 mm vs. 12.1 +/- 2.2 mm vs. 10.9 +/- 1.7
      mm). The correlation coefficients derived from comparisons of MRI vs. cath to
      echo vs. cath were similar for all dimensions except for isthmus length (P <
      0.01). MRI demonstrated aorto-aortic collaterals more frequently than echo, while
      echocardiography better demonstrated cardiac function and intracardiac anomalies.
      Both modalities detected the single patient with a long segment coarctation. We
      conclude that echocardiography and MRI provide similar definition of the coarcted
      thoracic aorta, and either test may be individually advantageous in specific
      clinical situations.

PMID- 9286534
TI  - Successful coronary pace-termination of ventricular tachycardia during coronary
      angioplasty.
AB  - Coronary pacing has been performed to treat bradycardias occurring during
      percutaneous transluminal coronary angioplasty (PTCA) using an angioplasty
      guidewire. We describe a case of a 62-year-old man who developed ventricular
      tachycardia (VT) during PTCA. The tachycardia was successfully terminated by
      overdrive pacing via an angioplasty guidewire.

PMID- 9286535
TI  - Pacing in the left heart--often forgotten because rarely needed.

PMID- 9286536
TI  - LAD-right ventricular fistula complicating PTCA: another case.
AB  - Coronary perforation caused by percutaneous transluminal coronary angioplasty
      (PTCA) occurs rarely and most often leads to communication to the pericardial
      space. We report a case where PTCA caused a coronary artery rupture and
      fistulization to the right ventricular outflow tract.

PMID- 9286537
TI  - Coronary artery fistula complicating coronary angioplasty: interventional
      cardiology turns into invasive cardiology.

PMID- 9286538
TI  - Acute infarction, intracoronary thrombolysis, and primary PTCA in pregnancy.
AB  - Acute myocardial infarction has an incidence in pregnancy of 1 in 10,000, with a
      mortality ranging from 37-50%. Mortality is increased if the infarct occurs in
      the third trimester, if the patient is under age 35 yr, if she delivers within 2
      wk of her infarct, and if she has a cesarean section. We present a case involving
      all four prognostically poor factors. The patient was treated emergently in the
      cardiac catheterization laboratory with intracoronary thrombolysis and primary
      PTCA of an occluded LAD. She had an uncomplicated recovery and subsequent
      delivery of a healthy child with no peripartum cardiac complications. A review of
      myocardial infarction in pregnancy follows.

PMID- 9286539
TI  - Resolution of exercise intolerance secondary to ischemic sinus node dysfunction
      following percutaneous transluminal angioplasty.
AB  - We report on a case of significant exertional symptoms secondary to occlusion of
      a nondominant right coronary artery proximal to the sino-atrial branch, with
      associated exercise-induced sinus node dysfunction. Successful angioplasty of the
      occluded right coronary artery restored a normal functional capacity and sinus
      tachycardia response to exercise.

PMID- 9286540
TI  - Stent placement in surgically reimplanted left main coronary artery in patient
      with anomalous origin of left main coronary artery from pulmonary artery.
AB  - Surgical repair of a 29-year-old woman's left coronary artery with an anomalous
      origin from the pulmonary artery was performed by reimplantation of the left main
      artery into the aorta, together with coronary artery bypass grafting. Subsequent
      stenosis of the reimplanted left main artery was treated with successful Palmaz
      Schatz stent placement.

PMID- 9286541
TI  - Delayed development of a pseudoaneurysm in the left circumflex artery following
      angioplasty and stent placement, treated with intravascular ultrasound-guided
      stenting.
AB  - Three months following satisfactory angioplasty and stent placement, a patient
      developed restenosis and a pseudoaneurysm of a coronary artery segment proximal
      to the previously stented area. The restenosis and the pseudoaneurysm were
      successfully treated with intravascular ultrasound-guided primary stenting. The
      delay in the appearance of the pseudoaneurysm attests to the chronic nature of
      the lesion.

PMID- 9286542
TI  - Giant left main coronary artery aneurysm in association with severe
      atherosclerotic coronary disease.
AB  - Aneurysms of the coronary arteries occur in 1.5-4.9% of coronary angiograms. Only
      a few cases of a giant aneurysm of the left main coronary artery in conjunction
      with severe atherosclerotic coronary disease have been reported. This report
      details the exceptional case of a 72-year-old patient with a giant "true
      saccular" aneurysm branched on the left main coronary artery. The development of
      an aneurysmal dilatation in conjunction with progression of coronary
      arteriosclerosis, observed from two different angiographic studies at an interval
      of 25 years, is very illustrative for evolutive atherosclerotic heart disease.
      This finding may support the hypothesis that atherosclerosis may be the common
      etiology for coronary aneurysmal dilatation.

PMID- 9286543
TI  - Indwelling pericardial drainage catheter break secondary to heart movement and
      catheter angulation.
AB  - We report on a case of a pericardial drainage catheter that severed on attempted
      removal. Surgery was required to remove the retained portion. No manufacturing
      defects were found on analysis of the catheter. Shear forces due to heart
      movement and the angle of catheter entry into the pericardium were the suspected
      reasons for the catheter disruption.

PMID- 9286544
TI  - Angioplasty followed by coronary stenting at the anastomotic site of saphenous
      vein bypass graft with the native vessel: a case that needs special procedural
      strategy.
AB  - In this report we describe a case in which a saphenous vein graft stenosis at the
      site of anastomosis with the left anterior descending artery (LAD) was dilated
      with a special Controlled Angioplasty Technology (CAT) balloon, and then stented.
      Balloon angioplasty and stenting at the site of anastomosis represents a
      technical problem because of diameter discrepancy and needs special attention in
      order to avoid minor or major complications.

PMID- 9286545
TI  - "Back-squeezing" of the clot: an unusual complication of primary coronary
      angioplasty.
AB  - Distal coronary embolism of thrombotic material is quite common in the setting of
      primary coronary angioplasty for evolving acute myocardial infarction.
      Embolization to another coronary artery is, however, much more uncommon. We
      report on a case in which a large thrombus migrated from the proximal left
      anterior descending artery (LAD) to the proximal left circumflex artery (CX)
      during inflation of the dilatation balloon. The putative mechanism was retrograde
      expulsion of the thrombus by the deploying balloon.

PMID- 9286546
TI  - Coil embolization of a coronary artery to pulmonary artery fistula from an
      antegrade approach.
AB  - Transcatheter embolization of coronary artery fistulae has become the therapy of
      choice for this uncommon lesion. We report a case in which transcatheter
      embolization was performed in a nine-year-old boy with a large fistula
      originating from the proximal portion of the left anterior descending artery and
      communicating with the pulmonary artery and the right coronary artery. The
      fistula was occluded 'antegrade' by cannulating the connection with the pulmonary
      artery to deliver occluding coils.

PMID- 9286547
TI  - Coronary sinus stenosis as a late complication of catheter ablation in Wolff
      Parkinson-White syndrome.
AB  - This report describes a patient who developed stenosis of coronary sinus and
      cardiac veins five years after application of electric shock currents to the
      posterior mitral annulus and posteroseptal region of the tricuspid annulus for
      ablation of a left posterior accessory pathway and a right posteroseptal
      accessory pathway. This is the first angiographic documentation of coronary sinus
      stenosis as a late complication of electric ablation of accessory pathway.

PMID- 9286548
TI  - Simultaneous biplane coronary and pulmonary arteriography: a novel technique for
      defining the course of an anomalous left main coronary artery originating from
      the right sinus of Valsalva.
AB  - We present a novel technique employing biplane cineangiography with simultaneous
      left coronary and pulmonary angiography to define the anomalous course of the
      left main coronary artery when it originates from the right sinus of Valsalva.
      These biplane cinearterlograms clearly define the relationship of the left main
      coronary artery to the great vessels, allowing confident delineation of the
      interarterial variant from the other, benign variants. We illustrate the
      advantages of this technique with two cases in which the course of the anomalous
      left main coronary artery was incorrectly diagnosed using standard coronary
      arteriography and magnetic resonance imaging.

PMID- 9286549
TI  - Pullback atherectomy with the Arrow-Fischell atherectomy device.
AB  - The Arrow-Fischell pullback atherectomy catheter is designed to circumferentially
      debulk and retrieve coronary atheroma. We performed pullback atherectomy before
      balloon angioplasty or stenting in 41 patients. The device crossed the target
      lesion in 38 (93%) and obtained tissue in 36 (88%). All procedures were completed
      successfully and without myocardial infarction, emergency cardiac surgery, or
      death. Complications included major spasm in 8 patients, postprocedural abrupt
      closure in 1, and otherwise uncomplicated arterial perforation in 2. Pullback
      atherectomy can be performed relatively safely, but is more difficult than
      balloon angioplasty, obtains less tissue than directional atherectomy, and is
      associated with significant limitations.

PMID- 9286550
TI  - Evaluation of an active coronary perfusion balloon device using Doppler flow wire
      during PTCA.
AB  - The aim of this study was to assess whether active coronary perfusion catheters
      (APC) can provide a sufficient coronary flow in large caliber vessels during
      balloon inflation. To prevent myocardial ischemia during PTCA, these APC may be
      employed. However, it is as yet unknown whether the active flow rate of these
      devices approaches the flow rate prior to PTCA during balloon inflation.
      Therefore, we measured the efficacy of the APC during balloon inflation in
      vessels supplying a large amount of myocardium. In 12 patients (1 female, 11
      males, 53 +/- 12.6 yr) with stenosed vessels (average diameter 3.4 +/- 0.26 mm),
      the coronary flow velocity was measured using a 0.014" Doppler guidewire, which
      was placed distally bypassing the balloon of the APC. The active perfusion
      balloon catheter was advanced through a 7F guiding catheter along a 0.014"
      guidewire. After removal of the guidewire, arterial blood being withdrawn from
      the side port of the femoral angioplasty sheath was pumped through the catheter
      to the distal coronary vessel. The perfusion volumes of the pump were set to
      different levels between 30 to 60 ml/min. Intracoronary flow rate was calculated
      by the angiographically assessed vessel luminal area [symbol: see text] average
      peak velocity [symbol: see text] 0.5. The mean coronary flow rate prior to PTCA
      was 43 +/- 17.7 ml/min. Maximum flow during PTCA was 55 +/- 19.6 ml/min. We found
      a good correlation between the preset external pump rate and the coronary flow in
      situ (r = 0.92). Pre-PTCA flow rates were achieved in 11 of 12 patients (92%)
      during balloon inflation. No relevant decrease in the arterial pressure occurred
      during dilation times of 4.6 +/- 1.63 min. Only two patients showed significant
      ECG changes during these balloon inflations. After an average follow-up period of
      13 +/- 6.3 mo, only one patient (8%) had a significant re-stenosis requiring the
      implantation of a stent. The combination of intravascular Doppler velocity
      measurements with quantitative coronary angiography offers the opportunity of
      exact online flow registration during angioplasty. Using APC, It is possible to
      maintain a sufficient coronary flow in the distal vessel during balloon inflation
      even in large vessels. Therefore, as compared with mechanical circulatory assist
      devices, coronary assist by APC is a little invasive, but according to our
      measurements it might be a sufficient tool for performing PTCA also in high-risk
      patients.

PMID- 9286551
TI  - Perfusion angioplasty: a rising or receding tide?

PMID- 9286552
TI  - Rupture of the arterial wall causes deflection in pressure time course during ex
      vivo balloon angioplasty.
AB  - A relation between restenosis and arterial lesions resulting from balloon
      angioplasty has been suggested in literature. Nevertheless, it is unclear to what
      extent angioplasty-induced arterial wall lesions contribute to the occurrence of
      restenosis. One problem is that arterial ruptures cannot be detected during
      balloon inflation. This study describes a method to detect ruptures in the
      arterial wall, based on deflections observable in the development of the balloon
      pressure. We performed ex vivo angioplasty with constant strain rate on 28 human
      femoral artery segments, showing deflections in 21 cases. In 20 cases wall
      rupture was confirmed histologically. From seven cases not showing deflections,
      four showed intact wall at microscopy. These figures result in a selectivity of
      the proposed method of 87 +/- 7% and a predictive value of the positive test of
      95 +/- 5%. We conclude that this method can enhance detection of arterial rupture
      during ex vivo angioplasty and may become important clinically.

PMID- 9286553
TI  - Quantitative evaluation of local drug delivery using the InfusaSleeve catheter.
AB  - BACKGROUND: Restenosis is the most common long-term complication after
      angioplasty. Local delivery of pharmacologic agents at the site of angioplasty
      holds promise as a means of achieving higher concentrations of drug in the
      arterial wall than can be obtained by systemic infusion. In this study, a novel
      local drug delivery catheter system, the InfusaSleeve catheter, was evaluated in
      a porcine coronary balloon injury model. The purpose of the study was to evaluate
      the efficacy of solute transfer to the arterial wall and the influence of varying
      supporting angioplasty balloon pressure. METHODS AND RESULTS: Ten pigs (total of
      22 arterial segments) underwent overstretch balloon injury (artery/balloon ratio
      1:1.29) with a standard angioplasty balloon. In 7 animals (16 arterial segments)
      horseradish peroxidase (HRP; 10 mg/ml) was administered locally after injury, by
      tracking the local infusion catheter as a sheath over the angioplasty balloon to
      the intended site of arterial drug delivery. Supporting angioplasty balloons were
      inflated to one of the three different pressures. In 3 pigs HRP (10 mg/ml) was
      administered intravenously. No significant arterial injury caused by the local
      delivery device was evident on histological examination (disruption of the
      internal lamina elastica, arterial media, or thrombosis). Radial concentrations
      of the HRP reaction product in the first 150 microns of the arterial wall were
      quantified against known standards by measurement of light transmission through
      tissue sections. Mean HRP concentrations were not significantly different from
      those obtained by intravenous infusion using a supporting pressure of 1 atm or a
      supporting pressure of 3 atm of the underlying angioplasty balloon. However, a
      supporting pressure of 6 atm resulted in a 6-fold greater mean HRP concentration
      in the arterial wall than that which could be achieved by systemic administration
      of an equal volume of tracer (P < 0.001). CONCLUSION: Thus solute can be
      delivered throughout the coronary media by the InfusaSleeve, with the magnitude
      of wall uptake related to support pressure. Local delivery at 6 atm support
      pressure produced substantially greater uptake than did systemic delivery.

PMID- 9286554
TI  - Ventricular perforation following stenting of left anterior descending artery.

PMID- 9286555
TI  - The UNOS Scientific Renal Transplant Registry.
AB  - 1. One-year graft survival rates for recipients of cadaver kidney transplants
      improved from 75% in 1988 to 83% in 1991 (p < 0.001). The one-, 5-, and projected
      10-year graft survival rates for cadaver donor transplants performed in 1991-1995
      were 84%, 60%, and 43% respectively. 2. One-year graft survival rates for
      recipients of living donor transplants also improved from 89% in 1988 to 93% in
      1991 (p < 0.001). The one-, 5-, and projected 10-year graft survival rates for
      living donor kidney transplants performed in 1991-1995 were 92%, 75%, and 62%
      respectively. 3. Diabetic patients received one-quarter of the cadaver kidneys
      transplanted from 1991-1995 and one third of diabetic patients received a
      simultaneous pancreas (SPK) transplant. One- and 5-year graft survival rates were
      81% and 54% for diabetics receiving a kidney transplant and 85% and 67% for SPK
      recipients, respectively. Patient survival was 10% lower for recipients of a
      kidney only transplant. 4. Sensitization to alloantigens, whether by pregnancy,
      transfusion, or graft failure resulted in about a 5% increased risk of early
      graft failure. Patients who developed broadly reactive anti-HLA antibodies before
      their first transplant had the same 5-year graft survival rate (60%) as
      unsensitized patients. Retransplanted patients who had not developed broadly
      reactive antibodies also had a 60% 5-year graft survival rate, compared with 50%
      for those with > 50% PRA. 5. Blacks received one-quarter of cadaver kidneys
      transplanted in 1991-1995. The one-year graft survival rate for Black first
      transplant recipients was 83% compared with 84% for Whites. After the first year,
      the graft loss rate among Blacks was almost double that for other racial groups
      (5.8 year half-life vs 11.3 years for Whites, p < 0.01). The 5-year graft
      survival rate was 49% among Blacks and 63% for Whites. Asian recipients had the
      highest one- and 5-year graft survival rates (89% and 70%, respectively). 6.
      Shared kidneys had a longer average cold ischemia time (30 hr) than kidneys
      transplanted locally (21 hr). Fewer than half of shared kidneys were transplanted
      to HLA-matched recipients. The 5-year graft survival rate for shared kidneys with
      zero or one HLA antigen mismatched was 68% compared with 59% for shared kidneys
      with more than 3 antigens mismatched and for locally transplanted kidneys (p <
      0.001). 7. The distribution of living donor relationships has changed
      substantially. When comparing transplants performed in 1988-1989 with those
      performed in 1994-1995, the number of living donor transplants increased by 80%,
      the fraction of offspring-to-parent grafts increased from 9-15%, the fraction of
      genetically unrelated donors increased from 4-10%, and the fraction of distant
      relatives increased from 2-6% of the living donor transplants. 8. The results of
      living donor transplants generally followed the degree of HLA compatibility. The
      one-year survival rate for HLA-identical sibling grafts was 96%, followed by 92%
      for one-haplotype matched sibling, parent and offspring donor transplants, 90%
      for unmatched sibling donors and 88% for spousal donors. Other unrelated donor
      transplants had a slightly higher one-year graft survival rate of 92%, which was
      more similar to the one-haplotype matched grafts.

PMID- 9286556
TI  - Recent findings concerning liver transplantation in the United States.
AB  - CENTERS: The growth in liver transplantation activity recorded by the Pitt-UNOS
      Liver Transplant Registry since October 1987 continued. However, for the first
      time since the establishment of the LTR, there was no net gain in the number of
      centers in 1995. The large differences in volume per center also diminished.
      PATIENTS: The age of pediatric recipients increased significantly in 1995, due to
      a decrease in the proportion of recipients under age one. For the first time, in
      1995 fewer than half of transplantations in children were for biliary atresia.
      The addition of bone marrow transplantations, for which collection began in 1994,
      accounted for half of the multi-organ transplantations in 1995. Many of the
      characteristics examined for adult recipients changed between 1994 and 1995. The
      proportion of Hispanic recipients increased. The mean age of adult recipients
      continued to increase, but there was not a significant change in the prevalence
      of positive CMV serology. Reversing a trend, the proportion of adult recipients
      awaiting transplantation outside of the hospital decreased between 1994 and 1995.
      As with children, the proportion of adult multi-organ transplantations which
      included bone marrow increased. Hepatitis non-A, non-B, or C and alcoholic liver
      disease (ALD) were the most common reasons for LTX in 1995. While the proportion
      of recipients with ALD alone decreased slightly, the proportion with ALD and
      hepatitis C increased from 1994 to 1995. OUTCOME: The cumulative probability of
      surviving (without retransplantation) for 8 years after initial transplantation
      was .71 (.60) for pediatric recipients. The one-year survival for pediatric
      recipients changed significantly over time with the increase from 1994 to 1995
      being similar to the increase between 1994 and prior years. Independent risk
      factors for survival among children included age, race, location awaiting
      transplantation, primary liver disease, and serum creatinine. Year of
      transplantation and bilirubin were independently associated with
      retransplantation-free survival, whereas multi-organ transplantation was
      associated with poorer patient survival. The cumulative probability of adults
      surviving (without retransplantation) for 7 years following LTX was .58 (.50).
      Independent risk factors were year of transplantation, age, location awaiting
      transplantation, primary liver disease, albumin, creatinine, and ABO match. Black
      recipients had poorer patient survival rates than other recipients whereas
      increased prothrombin time and CMV-positive donors were risk factors for
      retransplantation or death.

PMID- 9286558
TI  - Pancreas transplantation in the United States (US) and non-US as reported to the
      United Network for Organ Sharing (UNOS) and the International Pancreas Transplant
      Registry (IPTR).
AB  - As of November 1996, more than 8,800 pancreas transplants had been reported to
      the IPTR. There were 6,500 performed in the US, including more than 5,800 since
      the inception of the UNOS Registry in October 1987, and more than 1,000 in 1995.
      In Europe, more than 2,100 cases were reported to the IPTR, while fewer than 200
      have been done in other locations. This report analyzes cases reported since
      1987. In the US, BD has been used for the majority (92%). However, ED has
      recently increased in popularity, and for 1995, 15% of US cases were done by this
      method. In the SPK category results for 1994-1996 BD (n = 1,510) and ED (n = 221)
      were comparable, with one-year GSRs of 62% and 77%, respectively. When the 1987
      1996 US data for BD cases were analyzed according to the 3 major recipient
      categories, SPK transplants (n = 3,989); PAK transplants (n = 375) and PAK
      transplants (n = 229), patient survival rates were no different (92%, 92% and
      91%, respectively at one year). But one-year pancreas GSRs were significantly
      higher (p = 0.0001) in the SPK than in the PAK and PTA categories (79%, 60% and
      57%, respectively). In the SPK group, the one-year kidney GSR was 88%.
      Retransplants and primary transplants fared similarly in the SPK category, with
      one-year GSRs of 79% (n = 3,947) and 77% (n = 42), respectively. But in the PAK
      category, primary transplants did better, 62% (n = 275) versus 47% (n = 100)
      functioning at one year. The PTA category outcome was also better for primary
      than retransplants, with GSRs of 57% (n = 191) and 51% (n = 38) at one year. An
      improvement in GSRs could be shown over the analyzed time period for all
      categories; for 1994-1996 cases in the SPK (n = 1,516), PAK (n = 141) and PTA (n
      = 64) categories, one-year pancreas GSRs were 81%, 71% and 64%, respectively (p =
      0.004). The kidney GSR for 1994-96 SPK cases was 88% at one year. Preservation
      had minimal impact on outcome. In the SPK category, one-year GSRs for pancreases
      stored less than 12 (n = 1,400), 12-24 (n = 2,256) and more than 24 (n = 195)
      hours were 78%, 80% and 76%, respectively. The impact of FK506 immunosuppression
      on pancreas transplant survival was also analyzed for 1994-1996 cases. The
      results were comparable to those with CsA. For SPK cases, one-year GSRs were 82%
      with CsA (n = 1,247) and 81% with FK506 (n = 257). The one-year immunological
      loss rates were 2% and 3%, respectively. For PAK cases, one-year GSRs were 84%
      for FK506- (n = 42) and 65% for CsA- (n = 97) treated recipients (p < 0.04), and
      the immunological loss rates at one year were 11% and 7%, respectively. In PTA
      cases, the one-year GSRs were 66% with CsA (n = 37) and 64% with FK506 (n = 26)
      with immunological loss rates of 9% and 0%, respectively (p > 0.2). Outcomes were
      also compared according to whether recipients underwent induction immunotherapy
      with ALG/ATG/ATS, OKT3, or neither. In the SPK category, GSRs were 81% with OKT3
      (n = 1,600), 75% with ALG/ATG/ATS (n = 1,715) and 75% with neither (n = 45) (p <
      0.001). In the PAK category, the use of OKT3 (n = 81) was associated with lower
      graft survival rates than when ALG/ATG/ATS (n = 220) or neither (n = 49) was
      given (43%, 62%, and 54% at one year, respectively). In the PTA category the use
      of ALG/ ATG/ATS (n = 132) or OKT3 (n = 76) was associated with significantly
      higher graft survival (59% and 57%, respectively) than when neither (n = 13) was
      used (26% at one year). The effect of HLA-A,-B and -DR mismatching on outcome for
      US cases was determined on both overall graft survival rates and on risks for
      immunological loss. For SPK cases, the pancreas GSRs were significantly higher (p
      < 0.04) with zero-mismatched grafts (n = 30) than with higher degrees of
      mismatches (85% at one year versus 69%, 76% and 79% with one [n = 67], 2-3 [n =
      925] and 4-6 [n = 2,836] mismatches, respectively). For PAK cases GSRs were
      progressively higher with decreasing numbers of mismatches (100%, 75%, 58% and
      53% at one year with zero [n = 7], one [n = 35], 2-3 [

PMID- 9286557
TI  - Worldwide thoracic organ transplantation: a report from the UNOS/ISHLT
      International Registry for Thoracic Organ Transplantation.
AB  - 1. The number of heart transplant operations performed in the United States grew
      modestly as indicated by a 12% increase from 1990 (n = 2,108) to 1995 (n =
      2,360). From 1990 (n = 203) to 1995 (n = 871), lung transplant procedures
      increased by 329%. This trend has continued with 723 procedures performed in 1994
      and 871 (21% increase from 1994) reported for 1995. As in the US, the number of
      non-US heart transplants has leveled during recent years. 2. The number of heart
      transplant programs in the United States has remained relatively constant over
      the last 3 years with a decrease of 5 heart programs from 1995 to 1996. The
      number of centers performing lung transplantation has also leveled during the
      last 3 years with an increase of only 4 programs from 1994 to 1996. Non-US lung
      programs increased 90% from 1994 to 1995. 3. The most frequently reported
      indication for heart transplantation in the US has changed from coronary artery
      disease (40.9%) in previous registry reports to all cardiomyopathies (44.7%). For
      other thoracic transplants, the most frequently reported indications included
      cystic fibrosis (36.7%) for double-lung, emphysema/COPD (46.8%) for single-lung
      and congenital lung disease (41.2%) for heart-lung transplants. The most
      frequently reported diagnoses for thoracic transplantation outside the US
      included cardiomyopathy (48.5%) for heart, cystic fibrosis (36.0%) for double
      lung, idiopathic pulmonary fibrosis (26.5%) for single-lung and primary pulmonary
      hypertension (25.0%) for heart-lung transplants. 4. US heart transplant
      recipients were predominantly male (77.8%), 50-64 years old (51.1%) and white
      (82.7%). In contrast, US lung transplant recipients were predominantly female
      (52.9%), 35-64 years old (73.1%) and white (89.9%). No significant variance from
      the US recipient demographic profile was noted for non-US recipients in these
      analyses. 5. The one-year survival rate for US heart transplant recipients during
      recent years was fairly consistent, with only a 0.4% increase from 1990-1995.
      Improvement in the one-year US lung transplant survival rate was demonstrated by
      a rise from 35.3% in 1987 to 74.0% in 1995. The one-year survival rates at non-US
      centers were 76.0% for heart recipients and 64.5% for lung recipients in 1995. 6.
      The long-term thoracic patient survival rates in the United States were: 33.3% at
      12 years for heart, 43.7% at 5 years for lung and 27.6% at 10 years for heart
      lung recipients. Long-term survival rates for non-US cases were: 30.3% at 12
      years for heart, 44.8% at 6 years for lung and 19.8% at 10 years for heart-lung.
      7. The most important risk factor for US heart recipients at 1 month, 1 year, 3
      years and 5 years after transplantation was receipt of a previous heart
      transplant. Other substantial long-term risk factors included recipient age less
      than 1 year, donor aged 45-54, and non-white recipient. 8. The most important
      mortality risk factor in US lung recipients was the order of the transplant
      (primary or repeat). Diagnosis and ventilator use remained highly influential
      risk factors for mortality.

PMID- 9286559
TI  - The UNOS OPTN Waiting List and Donor Registry: 1988-1996.
AB  - 1. There were 49,233 registrations on the combined UNOS waiting list as of
      October 31, 1996, an increase of 207% over December 31, 1988. Of these, 69% were
      awaiting kidney transplantation, and 14.6% were awaiting liver transplantation.
      2. More than one-half of all patients on the UNOS waiting list on October 31,
      1996 were blood type O, 60% were White, 58% were male, and 56% were aged 18-49.
      3. Annual additions to the UNOS kidney waiting list grew from 11,909 in 1988 to
      17,635 in 1995. The largest increase in waiting list size was in the lung waiting
      list, which grew from 126 additions in 1988 to 1,706 additions in 1995. 4. For
      patients registering in 1994, median waiting times to transplant were longest for
      kidney registrants (842 days), followed by heart-lung registrants (612 days). The
      shortest waiting times for this cohort were experienced by liver registrants (173
      days). 5. In general, death rates per 1,000 patient years at risk have declined
      during 1988-1995. Death rates were higher for patients awaiting life-saving
      organs (liver, heart, lung, heart-lung) than for non-lifesaving organs (kidney,
      pancreas, kidney-pancreas). 6. There were 5,359 cadaveric and 3,215 living donors
      recovered in 1995, a 31% and 76% increase, respectively, over the numbers
      recovered in 1988. 7. The number of organs recovered per cadaveric donor
      increased from 2.98 in 1988 to 3.68 in 1995. At the same time, the number of
      organs transplanted per cadaveric donor recovered increased from 2.73 to 3.24. 8.
      Large increases were seen in the number of recovered donors who were liver (45
      81%), pancreas (14-24%), and lung (3-17%) donors between 1988-1995. 9. The number
      of cadaveric donors aged 50 or older has increased 172% from 1988 (475 donors) to
      1995 (1,292 donors). 10. The typical cadaveric donor in 1995 was a White male
      with blood type O, between the ages 18-34. In 1995, a typical living donor was a
      White female with blood type O, aged 35-49. 11. Between 1988-1995, the percentage
      of minority donation has increased for cadaveric donors (16.4-22.8%), and for
      living donors (24.0-27.5%). 12. The number of spouses or other unrelated living
      donors has increased from 4% in 1988 to 11% in 1995.

PMID- 9286561
TI  - Long-term results of solid organ transplantation. Report from the Eurotransplant
      International Foundation.
AB  - Graft survival of cadaveric kidney-only, liver-only and heart-only transplants,
      performed in the Eurotransplant area between 1987-1990, was analysed, up to 5
      years after transplantation. 1. HLA-A,-B,-DR mismatches had a statistically
      significant adverse influence on renal graft survival. 2. Kidney
      retransplantation was not found to be associated with a higher risk of graft
      loss, in contrast to liver and heart retransplantation. 3. The use of non-ideal
      donors (aged under 16 or over 55, non-head trauma donors) in renal
      transplantation should be re-evaluated, while elderly donors as well as elderly
      recipients jeopardized liver and heart transplant success rates. 4. A learning
      phase in liver and heart transplantation was evident from 1987-1990. 5. Time
      effect studies can be used to adopt individual monitoring schemes. A persistent
      risk of graft loss in renal transplantation was observed for transplants from
      older donors and transplants in older recipients; these grafts constituted a very
      vulnerable group. For liver and heart retransplants it was noted that once
      patients had survived the first postoperative month, their relative risk of graft
      failure was no longer significantly different from patients with a first
      transplant. A well-considered long-term monitoring scheme for heart allograft
      recipients who are over age 55 is justified, as these patients had a higher risk
      of failure compared with younger patients. The same would be advantageous for
      liver transplants that are performed because of underlying liver malignancies.

PMID- 9286560
TI  - The Canadian Organ Replacement Register.
AB  - The analyses presented in this chapter are a subset of the yearly audit of organ
      donation and transplantation in Canada published in the CORR Annual Report. They
      represent the collaborative efforts and the voluntary contributions of many of
      the transplant physicians, surgeons, nurses and coordinators in Canada. In
      Canada, organ donation has remained static at approximately 14 per million
      population. Despite many local and provincial as well as corporate initiatives,
      this rate is approximately half the current rate in many regions of the U.S.A.
      and Spain. The modest increases in transplant activity represent an increase in
      the use of living donors, reassessment of the traditional donor risk factors
      (including age) and expansion of the potential donors for each organ. Analysis of
      the renal transplant activity has determined that the likelihood of being
      transplanted during the first year on the list was less than 40%. A graft loss
      rate of 4% per year after the first year was observed for a cadaveric kidney,
      compared with graft loss rates of 3% and 2% per year for living-related and
      living-unrelated donor kidneys, respectively. Cox regressional analysis
      identified that the major determinants of patient survival were the transplant
      year, the region where the transplant was performed, the presence of diabetes,
      the recipient's age, and whether the kidney was from a living donor. Liver
      transplantation has increased each year at the transplant centers in Vancouver,
      Edmonton, London, Toronto, Montreal, and Halifax. Patient and graft survival
      rates have improved since 1985 and the most significant determinant of patient
      survival following transplantation was the patient's medical status at the time
      of transplantation. Living-related liver donor transplant programs have begun in
      London and Toronto. Pancreas transplantation remains limited across Canada, but
      with the development of new pancreas programs in Toronto and Halifax, an increase
      in the availability of this therapy for Type 1 diabetics is anticipated. Heart
      transplantation has recovered from a decline in 1991-1992 to approximately 6
      hearts per million population. There has been a trend towards better one- and 3
      year patient survival rates since 1985. With the development of a lung
      transplantation program in Winnipeg, lung transplantation has increased. This
      likely reflects increased utilization of the available donor lungs. A particular
      increase in double-lung transplants was noted.

PMID- 9286562
TI  - Kidney sharing by centers of the South-Eastern Organ Procurement Foundation.
AB  - 1. SEOPF centers historically have shared kidneys at a higher rate than the rest
      of the United States. 2. SEOPF centers transplanted better-matched kidneys than
      the rest of the nation despite transplanting a significantly larger percentage of
      "hard-to-match" black recipients. 3. Within SEOPF centers, a shared kidney was
      almost twice as likely to be a good match (zero-3 HLA antigen mismatches) as was
      a local kidney. 4. Within SEOPF centers, well-matched kidneys (zero-3 HLA antigen
      mismatches) had significantly better graft survival than did poorly-matched (4-6
      HLA antigen mismatches) kidneys. 5. SEOPF centers had one-, 2- and 3-year graft
      survival rates comparable to those of the rest of the nation. 6. SEOPF centers
      have proven the efficiency of ROP trays in predicting final crossmatch results
      for shared kidneys. 7. The SEOPF High Grade Match (HGM) algorithm has been
      successful in transplanting highly sensitized (current PRA > 40%) recipients. 8.
      The use of ROP trays in well-matched, highly sensitized recipients resulted in
      improved kidney availability. 9. Graft survival of HGM recipients was comparable
      to that of non-HGM recipients. 10. Despite longer cold ischemia times for HGM
      kidneys, there was no increased incidence of delayed graft function in these
      kidneys. 11. The HGM program accounted for 8.1% of the participating centers'
      activity and, thus, has not adversely impacted the majority of the centers' other
      patients. 12. The one- and 2-year graft survival data for HGM transplants were in
      accordance with the expected rates and were not statistically different from
      those of non-HGM transplants.

PMID- 9286564
TI  - Pediatric heart transplantation at Loma Linda: 1985 to 1996.
AB  - Pediatric heart transplantation at Loma Linda is now in its second decade with
      299 infants and children having received 309 transplant procedures. Overall
      survival is 73% with 10 year actuarial survival of 66% for all ages. Newborn
      recipients have a 77% actuarial survival at 11 years. As expected, acute
      rejection, infectious disease and technical issues are the most frequent causes
      of death. Posttransplant coronary artery disease (PTCAD) has been diagnosed in 22
      patients, an incidence of 9.5% of those patients surviving at least 1 year after
      transplantation. Seven children have undergone retransplantation for PTCAD with
      an actuarial survival at 3 years of 83%. Six children (2%) have been diagnosed
      with posttransplant lymphoproliferative disease. Long-term renal function is
      acceptable with average glomerular filtration rate of 79 ml/min/1.73 m2 and
      average creatinine beyond 5 years of 65 mmol/l (0.7 mg/dl). Most children in this
      population have heights and weights within the low normal range. Infant
      recipients who are now at least 6 years old are in an appropriate grade level in
      85% of cases. Ten year survival, with good clinical outcome, is achievable in
      this population.

PMID- 9286563
TI  - Report of the Japanese Central Bone Marrow Data Center.
AB  - The Japan Marrow Donor Program started to recruit donors at the beginning of 1992
      with the financial support of the Japanese government, and the first unrelated
      bone marrow transplantation arranged through this program was performed in 1993.
      Since 1992, about 82,000 donors and 4,400 patients have been registered. At least
      one HLA-identical donor has been found for 60% of the patients in the first
      search after the patients register with the JMDP, and as of the end of September
      1996, 880 patients had received bone marrow transplants from unrelated donors.
      The results of 19.7% of registered patients having received bone marrow
      transplants and 1.1% of registered donors having donated far exceed our
      forecasts. This is attributed to the high frequency of several haplotypes in the
      Japanese. However, no HLA-identical donors have been found for approximately 800
      registered patients so far. Thus, it is still necessary to increase the number of
      donors registered with the JMDP.

PMID- 9286565
TI  - Two decades of cardiac transplantation at the Columbia-Presbyterian Medical
      Center: 1977-1997.
AB  - Since its inception in 1977, the Cardiac Transplantation Service at Columbia
      Presbyterian Medical Center has performed more than 900 heart transplant
      procedures, with a one-year survival rate of approximately 80%, and a 5-year
      survival rate of approximately 60%. Throughout our 20-year experience, the
      criteria for eligibility both donors and recipients has widened to include older
      and "reanimated" donors for selected recipients, as well as an extensive
      experience with recipients bridged to transplantation with mechanical assist
      devices. Of particular interest in recent years has been the need for additional
      therapy for the highly sensitized transplant candidate and ultimate transplant
      recipient, whose immunosuppressive regimen must be continuously monitored and
      modified to ensure graft survival. In light of the persistent donor organ crisis,
      continued efforts are being developed to more accurately characterize the
      transplant candidate waiting list in order to identify those patients who may be
      better served by either medical management or an alternative surgical procedure
      to transplantation, including high-risk coronary revascularization and mechanical
      or biological assistance. Current research interests at CPMC include left
      ventricular assist devices, xenotransplantation, and management of both
      transplant coronary artery disease and immunologic sensitization. Ongoing
      investigations in these and other areas of transplantation have been established
      to encourage continued growth both within the field and at CPMC through the 21st
      century.

PMID- 9286566
TI  - Thoracic organ transplantation at Papworth Hospital.

PMID- 9286568
TI  - Status of liver and gastrointestinal transplantation at the University of Miami.
AB  - The liver transplant program at the University of Miami, established in 1987, was
      rejuvenated in June 1994 with the addition of new staff and expanded to include
      all organs of the gastrointestinal tract. Since its inception, 630 patients have
      been transplanted in the program. During the past 2 years we performed 349
      transplants in 318 patients (livers n = 323 in 298 patients, liver + kidneys n =
      13, liver + islet n = 10, liver + kidney + islets n = 1, liver + heart n = 10,
      liver + lung n = 1). These included 4 split-liver, 3 living-related, multiple
      reduced-sized and one "Domino" liver transplant. We have an active pediatric
      program and 10% of our transplanted patients are pediatric. Our overall patient
      and graft survival rates were 81% and 78%, respectively. The intestinal
      transplant program was launched in August 1994. To date we have performed 22
      intestinal transplants, in 9 adults and 13 children. These transplants included 4
      isolated intestinal, 11 combined liver-intestinal and 7 multivisceral
      transplants. Overall patient and graft survival rates were 55% and 50%,
      respectively. During the past 2 years several studies involving immunosuppressive
      agents were carried out: 1)Mycophenolate Mofetil (MMF) was used as induction
      therapy and as rescue therapy in patients with steroid-resistant rejection.
      Tacrolimus toxicity, and chronic rejection; 2) Neoral was compared with
      Tacrolimus in patients with Hepatitis C; and 3) MMF was added as triple therapy
      for the intestinal transplants. We used alpha interferon-2b (alpha-IFN) in
      hepatitis C positive patients in the early posttransplant period and found that
      it appears to be a safe drug. There was no increase in rejection in patients
      receiving alpha-IFN, and patient and graft survival were the same as in our
      overall patient population. A combination a-IFN with Ribavirin will be undertaken
      in the near future. The use of Lamivudine in hepatitis B patients was shown to be
      effective in preventing and treating recurrence of hepatitis B posttransplant.
      Unmodified donor bone marrow cells (DBMC) were isolated from the vertebral bodies
      of the same cadaveric liver donors. Donor bone marrow dose, number of cells
      and/or number (or timing) of infusions were investigated to determine which
      variables affected the ability of DBMC to engraft in the liver recipient. The
      long-term benefit of DBMC needs further follow-up. Although, our patient and
      graft survival for liver transplant recipients is comparable to other large
      centers nationally and internationally, we still have some challenges to
      overcome. These include: 1) control and prevention of recurrent HCV, 2) improved
      treatment for hepatocellular cancer pre- and posttransplant, and 3) treatment and
      prevention of chronic rejection. Intestinal transplantation remains an even
      greater challenge. Diagnostic tests to determine intestinal function need further
      development and although MMF has shown some promise in this field, newer
      immunosuppressive medications need to be investigated to prevent rejection and
      avoid over immunosuppression.

PMID- 9286567
TI  - The University of Toronto liver transplant program.
AB  - The University of Toronto liver transplant program began in 1985 at a time when
      the procedure had already evolved from an experimental form of surgery to an
      accepted treatment for many forms of liver failure. The program was established
      not only to provide clinical care for patients but also to address academically
      the barriers which impeded success. The program brought together experts in
      medicine, surgery, pathology, and the basic sciences of immunology, virology and
      molecular biology. Our group has had a special interest in transplantation for
      viral hepatitis. We demonstrated the role of HBV DNA as a prospective factor in
      both viral recurrence and survival. We further studied a number of agents to
      prevent re-infection including PGE, HBIG and more recently lamivudine. Although
      the short-term results of transplantation for HCV appear excellent, reinfection
      of the graft and development of chronic hepatitis and cirrhosis may make long
      term results problematic. Therefore, we have directed attention to studies of
      pathogenesis and treatment of HCV in liver transplantation. Our studies have
      demonstrated a unique role for ribavirin as an immunomodulatory agent which can
      benefit the course of posttransplant HCV. Future studies will examine combination
      therapy in an attempt to eradicate the virus. Our group also has been interested
      in PNF and FHF and have demonstrated a positive effect of PGE in this setting. As
      we look to the future, the greatest challenges facing transplantation are the
      shortage of organ donors and the toxic effects of long-term immunosuppression.
      Our group now has established research efforts both in tolerance induction and
      xenotransplantation which we feel are necessary to make transplantation an
      effective, universal treatment for end stage organ failure.

PMID- 9286570
TI  - Liver transplantation in Birmingham: indications, results, and changes.
AB  - The improvements in survival following liver grafting during the last five years
      reflect refinements in technique and in immunosuppressive regimens. Cirrhosis due
      to Hepatitis C and alcohol have become more common indications in this center.
      Efforts are being made to overcome the problems of donor organ shortage by using
      'marginal' donors and by splitting liver grafts.

PMID- 9286569
TI  - Update of the Adult and Pediatric Liver Transplant Program at the University of
      Michigan.
AB  - Significant technical innovations and improvements in immunosuppression have been
      introduced into our liver transplant program since its inception in 1985. The
      indications for transplantation have been extended to younger and older patients,
      and simultaneously more patients with comorbidities have been accepted for
      transplant. The net impact of these changes has been a continuing trend toward
      improved survival. Overall, patients with hepatitis B or malignancy have had poor
      survival rates. The introduction of prophylactic anti-hepatitis B immunoglobulin
      and lamivudine, and better selection of patients with malignancy may improve
      results for these patients in the future. As in other programs, our most vexing
      problem is the continuing scarcity of donor organs which has led to an ever
      expanding waiting list, more deaths while awaiting transplant, and more suffering
      before transplantation. The introduction of living donor hepatic transplantation
      will be of some help in alleviating this shortage. We are confident that the
      evolution of our program into a joint multidisciplinary structure will provide
      more efficient, convenient and cost-effective care to our patients.

PMID- 9286571
TI  - Thirty-seven years of renal transplantation in Oregon.
AB  - What we accomplish today as a matter of routine was only imagined by a few 4
      decades ago. The journey from that first successful kidney transplant in the
      1950s to the multidisciplinary, multiorgan transplant program of today has been a
      fascinating one. Although we attribute our current results to careful recipient
      selection and preparation, improvements in organ procurement and preservation,
      refinement of surgical techniques, improvement in histocompatibility techniques
      and organ sharing, improvements in immunosuppression and infection control, and
      careful monitoring of recipients, we and our patients have benefited from
      significant contributions from our colleagues in government and the law. The 4
      that come to mind are the provision of near-universal insurance coverage for end
      stage renal disease patients in 1972 under the Medicare program, the passage of
      brain death laws in the mid 1970s, the passage of the National Transplant Act in
      1984, and the passage of the Oregon required request law in 1985.

PMID- 9286572
TI  - Kidney transplantation, the Halifax experience.
AB  - In the absence of a national kidney sharing system in Canada, virtually all the
      cadaver kidneys we transplant come from donors within the 4 provinces we serve.
      Currently the only criteria we use for recipient selection of cadaver kidneys,
      apart from ABO blood group matching and a negative anti-T-cell crossmatch, are
      good HLA match and transplant wait-list seniority. All transplant recipients
      receive CsA-based immunosuppression. Antibody induction is used only for repeat
      transplants and pediatric transplants. Recipients of first cadaver kidney
      transplants with zero HLA-DR mismatches have significantly better graft survival
      than those with mismatches. Graft and patient survival rates for first cadaver
      transplants continue to improve within the CsA era, and are comparable to those
      seen in centers routinely using antibody induction and routine sequential
      quadruple immunosuppression. Chronic graft nephropathy continues to be the most
      important cause of graft loss after the first year, unchanged over the past 2
      decades, followed closely by death with a functioning kidney. The latter is a
      more important cause of loss in recipients older than age 60, and in recipients
      of HLA-identical live donor transplants. Repeat cadaver transplant recipients
      have a 5-year graft survival rate today equivalent to that seen with first
      cadaver transplants. Graft loss from acute rejection is modest, but kidneys
      requiring rescue therapy for steroid-resistant rejection have significantly
      poorer one- and 5-year graft survival and ultimately are lost from rejection.
      Patients with HLA-identical live-related donor transplants have better long-term
      survival with CsA than with azathioprine due to a decrease in graft loss from
      chronic rejection. Pre-transplant sensitization has an adverse effect on graft
      survival for haploidentical but not HLA identical live-related transplants.
      Patients over age 60 have equivalent graft survival to younger recipients for at
      least 7 years, and should not be precluded from receiving transplants by age
      alone. Prolonged CIT > 24 hours is associated with a significantly increased
      incidence and duration of ATN and need for dialysis, significantly increased
      early and late graft loss from acute and chronic rejection respectively,
      significantly reduced QALY's, and significantly higher early and late costs of
      transplantation.

PMID- 9286573
TI  - Thirty-two years of renal transplantation in Zurich.
AB  - This overview of the last 3 decades of renal transplantation at our center
      depicts the development from the early phase of clinical transplantation to the
      development of a standardized multiorgan transplant program. Between 1964 and
      1996, a total of 1,703 kidney transplants were performed at the University of
      Zurich Hospital in Switzerland. Due to a relatively active program in the early
      years of renal transplantation our data provide some useful information on the
      long-term results of renal transplantation. We observed a steady improvement in
      outcomes following transplantation during the first 2 decades of our program
      paralleled by an improvement in graft half-life. In the last decade, however, the
      demographic characteristics of our recipient population have changed gradually,
      leading to an increased proportion of diabetics and elderly patients. Thus,
      during the past decade, transplant outcomes, in terms of early graft and patient
      survival, have stagnated. The increased proportion of diabetics being accepted
      for transplantation has helped to establish simultaneous kidney and pancreas
      transplantation as a routine procedure, thereby offering these patients the
      prospect of long-term rehabilitation. In order to increase the number of
      available kidneys for transplantation we have adopted 2 strategies. First, we
      have successfully used donor kidneys from non-heart-beating donors. Results
      achieved with this method can be equivalent to transplantation of organs from
      heart-beating donors when certain criteria are respected. Second, we are
      increasingly performing kidney transplants from living-related donors and hope to
      further expand our activities in this direction in the future.

PMID- 9286574
TI  - Evolving strategies in immunosuppressive therapy: the Emory experience.
AB  - We have reviewed our experience with various immunosuppression regimens over the
      past 11 years in 2,065 renal transplant recipients. Patients received triple-drug
      maintenance therapy with CsA, imuran and prednisone following either no induction
      therapy or treatment with polyclonal (PCA) or monoclonal (MCA) antibody. The most
      recent immunosuppressive regimen has included CsA, MMF, and prednisone without
      induction therapy. We observed that those patients receiving PCA had a better
      graft survival 5 years after transplantation than recipients with MCA induction
      or those receiving standard triple drug therapy without induction. Patients
      receiving MMF experienced superior one-year graft survival compared with those
      receiving induction with PCA, MCA or standard triple drug therapy. A similar one
      year graft survival rate for both Black and White recipients was observed in the
      MMF group and raises the possibility of achieving improved long-term graft
      survival in Black recipients with a MMF-based immunosuppression strategy. Our
      experience indicates that excellent short-term graft survival can be achieved
      with an immunosuppressive protocol of MMF, CsA and prednisone without induction.
      Graft survival in MMF-treated recipients was equal to or superior to that which
      we previously achieved with induction therapy.

PMID- 9286575
TI  - Single-center analysis of 468 first cadaveric kidney allografts with a uniform
      ATG-CsA sequential therapy.
AB  - Progress in clinical management and sophistication of immunological treatment of
      kidney allografts depend upon continuous reassessment of the risk factors related
      to pre- and post-graft information according to the therapeutical strategies
      used. We studied predictive factors of long-term graft survival (up to 9 years)
      and of kidney graft function at one year after surgery in a single-center
      population of 468 first cadaveric kidney recipients treated with a uniform
      immunosuppression induction regimen of anti-thymocyte globulin, followed by
      cyclosporine A. The statistical analysis showed that long-term graft survival was
      highly correlated with the occurrence of one or more acute cellular rejections
      and with the timing of these episodes. In addition, this uniformly treated series
      of patients confirmed the potential importance of gender matching. The magnitude
      of anti-HLA immunization and delayed graft function were also strongly linked to
      low graft survival rates. We found no significant influence of HLA matching, with
      serological HLA typing, on graft loss. The quality of graft function at one year
      was found to be a strong prognostic factor of long-term graft survival. In
      addition, the impact of pre- and post-graft parameters were studied in terms of
      prediction of one-year graft function. A stepwise multivariate analysis showed
      that graft function at one year was a multivariate phenomenon strongly correlated
      with a history of acute rejection episodes and with donor and recipient age.
      However, these 3 factors could account for only 15% of the graft function
      deterioration, the remaining 85% might be explained in part by chronic
      cyclosporine toxicity and/or chronic rejection.

PMID- 9286576
TI  - Results of renal transplantation five to twenty-six years after surgery, using
      azathioprine and low-dose prednisolone as sole immunosuppression.
AB  - This paper describes the results of renal transplantation carried out in a single
      center from 10-26 years ago. Three hundred and eighty-six recipients received 440
      grafts, 400 were cadaver grafts and 40 were from living donors, including one
      unrelated donor whose kidney was removed during an operation. All patients
      received immunosuppression with azathioprine and low-dose steroid. 1. Over the
      whole period, 1968-1986, 46% patients remain alive. The actual total patient
      survival was 65% for 1986 transplants, 51.7% for 1981 transplants, 37.1% for 1976
      transplants and 31.2% for those transplanted 25 years ago. 2. Actual overall
      graft survival is 39.5% for the whole period. 3. Fifty-seven percent of living
      related donor grafts survived over the whole period, including 48% of parental
      grafts and 69% of sibling grafts. 4. Ten years after transplantation, 54.2% of
      grafts carried out in 1986 are functioning, as are 40% of those transplanted in
      1981, and 29% of those done in 1976 or before. In all 37% of first cadaver grafts
      continue to function, while 62% have failed. However 35 patients died with a well
      functioning graft, due to either cardiovascular disease or neoplasia in 91% of
      cases. 5. Thirty-four percent of second cadaver grafts function over the whole
      period, 65.8% have failed. Only one of 9 third cadaver grafts, dating from 1975,
      continues to function.

PMID- 9286577
TI  - Pancreas transplantation at the University of Maryland.
AB  - 1. The University of Maryland pancreas transplant program was initiated in July
      1991. Through December 1996, 230 pancreas transplants were performed (145 SPK, 64
      PAK, 21 PTA). Overall one-year patient and graft survival rates were 95.5% and
      78.9%, respectively. 2. The majority of pancreases have been transplanted
      simultaneously with a kidney. The one-year patient, pancreas and kidney survival
      rates for SPK transplants were 95.5%, 91.9%, and 82.5%, respectively. 3. Pancreas
      alone (PA = PAK or PTA) transplants have represented an increasing proportion of
      the total in recent years. Although the results of PA were previously inferior to
      SPK transplants, recent developments have made the outcomes equivalent. The
      advent of FK and MMF have sharply reduced graft losses due to irreversible
      rejection. Percutaneous pancreas biopsy now provides a safe and effective means
      to diagnose acute rejection in a timely manner. Anticoagulation protocols have
      markedly reduced the risk of idiopathic postoperative graft thrombosis. The most
      recent series of 71 PA cases at our center had a one-year graft survival rate of
      75.8% overall, and 88.2% for the 61 technically successful ones. 4. The most
      widely practiced pancreas transplant technique in the US today includes bladder
      drainage of exocrine secretions. This results in a high incidence of bladder
      complications, which can be avoided by enteric exocrine drainage. The most recent
      series of pancreas transplants at the University of Maryland have been enteric
      drained, encompassing about half of all cases. Adoption of this technique has
      eliminated bladder complications, and has not been associated with an increase in
      anastomotic leaks, infectious complications or graft loss. 5. Most pancreas
      transplants have had systemic venous drainage via the iliac vein. We recently
      adopted the portal venous drainage technique, since it eliminates the peripheral
      hyperinsulinemia associated with systemic drainage, and may therefore improve
      lipid metabolism and possibly reduce the risk of progression of atherosclerosis.
      Early results have been favorable. 6. At present the major determinant of
      pancreas transplant outcome is donor quality. We have emphasized the importance
      of using pancreases free of fatty or fibrotic transformation, which have been
      skillfully procured from young, stable, non-obese donors.

PMID- 9286579
TI  - Review of transplantation--1996.

PMID- 9286581
TI  - A multi-factor analysis of kidney graft outcomes at one and five years
      posttransplantation: 1996 UNOS Update.
AB  - 1. GENERAL: Here we updated our analysis of the UNOS Kidney Registry for the
      compound effects of 26 transplantation factors on graft survival within 2
      consecutive posttransplantation risk periods. During the early risk period,
      83,867 kidney-only recipients were followed through one year, and, in the second
      (chronic) risk period, 66,358 recipients whose grafts survived beyond one year
      were followed for 5 years after transplantation. 2. SHORT-TERM EFFECTS: From the
      analysis, the top (< 2% of assignable variation) factors influencing one-year
      graft survival rates were ranked as follows: 1) living-related and living
      unrelated donor transplants were preferred; 2) some transplant centers had
      outstanding results; 3) kidneys from stroke victims displayed poor results; 4)
      recipients with PRA > 80% demonstrated poor survival; 5) patients transplanted
      before 1991 had poor results; 6) increasing numbers of HLA-ABDR mismatches
      decreased survival; 7) cold ischemia times beyond 24 hours diminished survival;
      8) kidneys from younger and older donors impaired survival; 9) regrafting was
      detrimental, 10) Asians and Hispanics enjoyed superior results; 11) recipients
      with restricted activities pretransplantation were at higher risk of early graft
      failure; and 12) high (> 30 kg/m2) body mass recipients demonstrated lowered
      rates. 3. LONG-TERM EFFECTS: Fewer net factors influenced graft survival beyond 1
      year through 5 years. The following 9 factors, each explaining > 2% of the
      assignable variation in conditional 5-year graft survival, were ranked and
      yielded poor results: 1) older (> 65) donors; 2) Black recipients; 3) poor
      transplant centers; 4) male recipients; 5) kidneys from cadaver or living
      parental donors; 6) transplantation prior to 1991; 7) stroke donors; 8) non-zero
      HLA-AB mismatched transplants; and 9) teenage recipients. 4. IMPACT ON KIDNEY
      ALLOCATION: This UNOS data analysis combined with other recent multi-center
      studies suggest that the criteria for kidney allocation need contain just 2
      components in order to maximize long-term survival-an immunologic factor
      (avoiding HLA mismatches) and a non-immunologic factor (a senior citizens pool to
      receive older donor organs).

PMID- 9286578
TI  - Allogeneic cell-mediated immunotherapy using donor lymphocytes for prevention of
      relapse in patients treated with allogeneic bone marrow transplantation for
      hematological malignancies.
AB  - Two major causes of treatment failure in allogeneic BMT for leukemia are graft
      versus host disease (GVHD) and leukemic relapse. Acute GVHD, mediated by
      alloreactive donor T lymphocytes originating from the transfused marrow is the
      most significant cause of transplant-related morbidity and mortality, despite the
      use of combined prophylaxis with cyclosporine and methotrexate. Effective
      prevention of GVHD can be accomplished by depletion of donor immunocompetent T
      cells from the marrow prior to its infusion. Depletion of lymphocytes, however,
      prevents the immune mediated interaction of donor T cells against residual host
      tumor cells--the graft versus leukemia (GVL) effect, which significantly
      contributes to the curative effect of allogeneic BMT. It is still unsettled to
      what extent GVH and GVL are unseparable or closely related phenomena, and a major
      question remains whether it would be possible to retain the beneficial
      antileukemic effects of donor T cells and at the same time prevent or control the
      risk of GVHD. We have adopted a policy by which an allogeneic BMT is conducted
      with T cell depleted marrow to minimize the risk of severe acute GVHD, followed
      by stepwise administration of fresh unirradiated donor lymphocytes for prevention
      of leukemic relapse. Our data show that the overall relapse free survival was
      significantly better for patients receiving preventive posttransplant donor
      lymphocytes, predominantly when transplant was performed in 1st or 2nd CR.

PMID- 9286582
TI  - Immunosuppressive regimens and their effects on renal allograft outcome.
AB  - The distribution and effectiveness of different immunosuppression protocols among
      recipients of first cadaver donor renal transplants reported to the UNOS
      Scientific Renal Transplant Registry whose graft survived at least 14 days after
      transplantation were analyzed. The results showed that between 1988-1993, 50-60%
      of recipients received triple therapy regimens including cyclosporine,
      azathioprine and prednisone (CAP). An additional 20% received CAP with antibody
      induction therapy (OKT3 or ALG). After 1993, there was an increase in the use of
      other drug combinations which include FK506 and, more recently, Neoral and
      mycophenylate mofetil. Patient survival was 90% at 3 years regardless of the
      immunosuppressive protocol. The 3-year graft survival rate was 75% under
      cyclosporine-based protocols, but was 79% for more recent recipients treated with
      FK506 (p = 0.015). Antibody induction protocols were not used more frequently for
      high-risk patients, including those with broadly reactive anti-HLA antibodies,
      pediatric recipients, transplants with delayed graft function and those with
      prolonged cold ischemia times. When induction therapies were reported for these
      higher risk transplants, there was no noticeable improvement in graft survival
      rates after excluding failures within the first 2 weeks. Any benefit of antibody
      induction must therefore be manifest with the first 2 weeks after
      transplantation. Induction protocols significantly reduced the incidence of
      rejection episodes (prior to hospital discharge) from 31% for those treated with
      CAP to 12% for those with antibody induction (p < 0.01), however, 24% of those
      given induction had at least one rejection between discharge and 6 months
      compared with only 18% of those treated with CAP without induction (p < 0.01).
      Although graft outcomes might be significantly influenced by the dosing and
      timing of immunosuppressive drugs, among the different combinations of drugs
      analyzed, only FK506 resulted in improved graft survival and half life. With the
      rapid proliferation of newer drugs and immunosuppressive strategies during 1996,
      it will be interesting to follow the course of these very recent transplants with
      regard to the effectiveness of changing immunosuppression.

PMID- 9286583
TI  - Immune responsiveness and renal transplantation.
AB  - Children and young adults produce lymphocytotoxic antibodies in response to blood
      transfusions more frequently than older patients. Young transplant recipients
      also have a higher incidence of rejection episodes, which lends support to the
      concept that young age is associated with a state of heightened immune
      responsiveness to alloantigens. Heightened immune responsiveness, however, does
      not explain the lower graft survival reported for Black transplant recipients.
      Black recipients have an increased rate of DGF, whose origin remains to be
      elucidated.

PMID- 9286584
TI  - HLA matching.
AB  - 1. HLA matching exerts a profound influence on graft outcome. The difference in 3
      year graft survival rates between best and worst matched cases was 17% for first
      grafts and 18% for retransplants. This HLA matching effect persists despite
      recent improvements in graft outcome. The matching effect at 3-years was 12% for
      transplants since 1991. 2. Surprisingly, HLA matching is especially important for
      recipients over age 60. The increase in the HLA matching effect to 20% in
      patients older than 60 can be attributed to the additive effects of HLA matching
      on both functional and patient survival. Consequently, graft survival for zero-MM
      recipients is similar for patients older and younger than age 60. 3. The
      difference in 3-year survival between zero and 0-MM kidneys was 10% for White and
      15% for Black recipients. 4. Transplants with zero-broad but split A,B mismatches
      had graft outcomes similar to one-A,B,DR MM kidneys. Split DR MM did not affect
      the outcome of zero-MM kidneys. 5. HLA-matched transplants can be classified
      according to the degree of identity between the donor and recipient: 6-antigen
      match, phenotypic match, and zero-MM. Outcome for zero-MM was lower in
      transplants before 1990, but the 3 types have similar outcomes in recent
      transplants. The change in UNOS matching policy in 1995 to include zero-MM
      kidneys doubled the number of shared kidneys. 6. HLA typing from over 150 centers
      resulted in an error rate for shipped kidneys of less than 5%. Donor antigens
      retyped at the recipient center resulted in identical antigens for 70% of cases,
      a broad DR MM for 2.2%, and an A,B MM in 2.6% of the retyped cases. 7. Although
      increasing cold ischemia time (CIT) had a deleterious effect on survival of MM
      kidneys, no effect was seen for zero-MM kidneys. 8. An effect of a possible sex
      linked minor histocompatibility antigen was demonstrated with improved outcome
      for male to male zero-MM cadaveric and parent-to-child transplants. 9. Zero-MM
      kidneys from pediatric donors and donors older than 60 years of age had poorer
      outcome than MM kidneys before 1991, but the recent experience shows a matching
      effect even with these marginal donors.

PMID- 9286585
TI  - HLA amino acid residue matching.
AB  - 1. HLA amino acid sequences have been defined for 77 A- and 176 B-locus antigens.
      Amino acid polymorphisms occurred at 80 A- and 74 B- sequence positions. 2. The
      majority of amino acid substitutions occurred in regions involved with peptide
      binding. A surprisingly large number of substitutions were in the alpha-3 regions
      of the molecule. 3. Graft outcome in cadaveric and living donor transplants was
      calculated for mismatches for every possible amino acid allele. 4. Two-thirds of
      the HLA-A and -B locus antigens used for solid organ allocation had disparate
      frequencies in White and Black recipients. Only 6 antigens were found in over 20%
      of White recipients. 5. Five-year survival for first transplants was 66% for zero
      DR, zero-residue mismatched kidneys compared to 59% for kidneys with mismatches.
      Half-life for residue matched kidneys was 11 years compared with 8 years for
      kidneys with mismatches. 6. Mismatches for all of the A-locus residues and the
      majority of B-locus residues were correlated with positive crossmatches. 7. None
      of the crossmatches for highly sensitized patients with zero-A,B,DR mismatches
      were positive; 30% of zero-residue mismatched patients had a positive crossmatch
      compared to 70% of cases with mismatches.

PMID- 9286586
TI  - Organ Procurement Organization and transplant center effects on cadaver renal
      transplant outcomes.
AB  - 1. A majority of transplant centers had significant improvements in cadaver donor
      kidney graft survival rates since 1991. A 10% or greater increase in one-year
      graft survival rates was reported by 36 of 128 large transplant centers. 2. When
      transplants were grouped according to the organ procurement agency that procured
      the kidney, large variations in one-year graft survival rates among 65 OPOs were
      noted. The "OPO effect" was of a magnitude similar to that of the "center effect"
      when analyzed separately. 3. Fourteen OPOs with the lowest graft survival rates
      procured a significantly higher fraction of kidneys from older, hypertensive or
      Black donors and donors whose deaths were not from motor vehicle accidents.
      Transplants were more often given to Black recipients, and kidneys were less
      frequently shared compared with 15 OPOs with the highest graft survival rates. 4.
      Significantly higher proportions of non-Black donors and recipients, patients
      with no activity limitation at the time of listing, patients working fulltime at
      the time of transplantation, and patients on dialysis less than one year were
      more frequently transplanted at 21 centers with excellent one-year graft survival
      rates compared with centers in groups with poorer results. 5. Increased numbers
      of mismatched HLA-B,DR antigens were detrimental to graft survival at centers
      with good or fair one-year graft survival rates, but had a minimal effect at
      centers with excellent results. 6. The OPO effect on graft survival rates was
      significantly associated with the center effect. Kidneys procured by OPOs
      associated with low graft survival rates and transplanted at centers with low
      graft survival rates resulted in the worst graft outcome. Interestingly, kidneys
      procured by OPOs associated with high graft survival rates, but transplanted by
      centers with low graft survival rates had better outcomes than kidneys from OPOs
      with lower graft survival rates. 7. Based on univariate analyses, the center and
      OPO effects ranked third and fifth among 16 significant factors. However, after
      adjusting for these 16 potentially confounding variables using a multivariate Cox
      regression model, the differences between the best and worst center and OPO
      groups were the fourth and eleventh most detrimental risk factors on graft
      outcome, respectively.

PMID- 9286587
TI  - Risk rate and long-term kidney transplant survival.
AB  - The findings from the UNOS Scientific Renal Transplant Registry are summarized in
      the following table. We've also provided our opinions on ways to influence the
      risk factors in the Discussion section. [table: see text]

PMID- 9286589
TI  - Worldwide transplant center directory.

PMID- 9286588
TI  - World transplant records--1996. Patients who currently have functioning
      transplants.

PMID- 9286590
TI  - Possible roles for Wnt genes in growth and axial patterning during regeneration
      of the tail in urodele amphibians.
AB  - Urodele amphibians are nearly the only adult vertebrates able to regenerate their
      missing or amputated tail. An interesting aspect of this biological model lies in
      the ability of regenerates to differentiate the spinal cord (SC), the vertebral
      cartilage, and muscles. The main questions addressed in this study concern the
      possible roles of Wnt genes in these regenerative processes. We have previously
      reported the expression pattern of a Pleurodeles Waltl wnt-10a gene (Pwnt-10a) in
      tail blastema (Caubit et al. [1997] Dev. Dyn. 208:139-148). We report here the
      cloning and tissue distribution of three additional Wnt genes (Pwnt-5a, Pwnt-5b,
      and Pwnt-7a) in adult and regenerating tail tissues and in the central nervous
      system (CNS) of adult newt. In adult and regenerating tails, Pwnt-5a and Pwnt-5b
      transcripts exhibit a graded distribution along the antero-posterior (A-P) axis,
      the maximal accumulation of these transcripts being detected in the mesenchyme
      within the subectodermal apical region of the normal tail and blastema. In
      contrast to Pwnt-5a and Pwnt-5b, Pwnt-7a is expressed in adult normal tail skin
      and in the epidermis of the regenerating tail. In the adult CNS, Pwnt-5a, Pwnt
      5b, Pwnt-7a, and Pwnt-10a genes are expressed in sharp overlapping but not
      identical domains along the A-P axis. The sustained expression of Wnt genes in
      the adult newt and the spatial distribution of transcripts in adult and
      regenerating tail tissues suggest roles of these genes in continuous growth
      capacities in the urodeles and may explain the ability for CNS and tail
      regeneration.

PMID- 9286591
TI  - Sequence and developmental expression of AmphiTob, an amphioxus homolog of
      vertebrate Tob in the PC3/BTG1/Tob family of tumor suppressor genes.
AB  - Tob is a member of the PC3/ BTG1/Tob family of vertebrate tumor suppressor genes;
      its expression is known to inhibit proliferation of cells in vitro, but its
      possible roles during normal development have not been investigated previously.
      The present study concerns the structure and developmental expression of AmphiTob
      in an invertebrate chordate, amphioxus. This is the first investigation of any
      Tob gene during embryological development. The 311 amino acid AmphiTob protein is
      similar to vertebrate Tob but lacks the C-terminal PQ-rich domain of the latter.
      In early embryos of amphioxus, in situ hybridization first reveals AmphiTob
      expression in the hypoblast at the gastrula stage on the likely dorsal side of
      the embryo. During subsequent development, expression is seen in several tissues
      of the ectoderm, mesoderm, and endoderm. The most striking expression domains are
      in the developing somitic musculature and dorsal nerve cord. In the medial wall
      of each somite, AmphiTob is expressed strongly by cells destined to differentiate
      into the axial trunk muscles; this pattern persists until late in the larval
      stage, evidently because undifferentiated cells are continually becoming myogenic
      as the muscles grow. Nerve cord cells conspicuously transcribe AmphiTob from the
      late neurula until the early larval stage: Expression occurs in a few cells
      scattered along the nerve cord and in a group of cells located in the cerebral
      vesicle (in a region presumably homologous to the vertebrate diencephalic
      forebrain). During development, an intense and transitory transcription of
      AmphiTob may be an early event in cells exiting the cell cycle in preparation for
      differentiation.

PMID- 9286592
TI  - Deficiency screen based on the monoclonal antibody MH27 to identify genetic loci
      required for morphogenesis of the Caenorhabditis elegans embryo.
AB  - The monoclonal antibody MH27 recognizes an adherens junction protein present
      around hypodermal cells in the pharynx and the intestine. By using this antibody
      and an antiserum against the LIN-26 protein, which is present in hypodermal and
      glial-like cells, I have examined the morphogenesis of the embryo in embryos
      homozygous for 91 chromosomal deficiencies that cover approximately 74% of the
      Caenorhabditis elegans genome. Most deficiencies were found to affect both the
      morphogenesis of the embryo and the organogenesis of the pharynx. By contrast,
      the intestine was generally normal. I have classified deficiencies according to
      their hypodermal staining abnormalities. I identified a few deficiencies that
      appeared to affect more specifically anterior-directed migration of hypodermal
      cells or extension of the margins of ventral hypodermal cells, integrity of
      hypodermal membranes, elongation of the embryo, and hypodermal cell fusions. This
      work opens the way for a genetic analysis of morphogenesis in C. elegans.

PMID- 9286593
TI  - Mouse clavicular development: analysis of wild-type and cleidocranial dysplasia
      mutant mice.
AB  - Cleidocranial dysplasia (CCD) is an autosomal dominant disease characterized by
      hypoplasia or aplasia of clavicles, open fontanelles, and other skeletal
      anomalies. A mouse mutant, shown by clinical and radiographic analysis to be
      strikingly similar to the human disorder and designated Ccd, was used as a model
      for the human disorder. Since malformation of the clavicle is the hallmark of
      CCD, we studied clavicular development in wild-type and Ccd mice. Histology and
      in situ hybridization experiments were performed to compare the temporal and
      spatial expression of several genes in wild-type and Ccd mutant mouse embryos.
      Bone and cartilage specific markers--type I, II, and X collagens, Sox9, aggrecan,
      and osteopontin were used as probes. The analyses covered the development of the
      clavicle from the initial mesenchymal condensation at embryonic day 13 (E13) to
      the late mineralization stage at embryonic day 15.5. At day 13.5, cells in the
      center of the condensation differentiate into characteristic precursor cells that
      were not observed in other bone anlagen. In the medial part of the anlage these
      cells express markers of the early cartilage lineage (type II collagen and Sox9),
      whereas cells of the lateral part express markers of the osteoblast lineage (type
      I collagen). With further development the medial cells differentiate into
      chondrocytes and start to express chondrocyte-specific markers such as aggrecan.
      Cells of the lateral part differentiate into osteoblasts as indicated by the
      production of bone matrix and the expression of osteopontin. At day 14.5 a
      regular growth plate has developed between the two parts where type X collagen
      expression can be demonstrated in hypertrophic chondrocytes. The data indicate
      that the medial part of the clavicle develops by endochondral bone formation
      while the lateral part ossifies as a membranous bone. The clavicle of Ccd mice
      showed a smaller band of mesenchymal cell condensation than in wild-type mice.
      Cells of the condensation failed to express type I and type II collagen at E13.5.
      In the lateral part of the clavicle type I collagen expression was not detected
      until E14.5 and osteopontin expression only appeared at E15.5. At E15.5, a small
      ossification center appears in the lateral part which is, in contrast to the wild
      type clavicular bone, solid and without primary spongiosa as well as bone marrow.
      In the medial portion, type II collagen expression and endochondral ossification
      never occurs in Ccd mice; this portion of the clavicle is therefore missing in
      Ccd.

PMID- 9286594
TI  - Expression of fibroblast growth factor receptors (FGFR1, FGFR2, FGFR3) in the
      developing head and face.
AB  - Fibroblast growth factors may play an important role in the differential growth
      of the skull, brain, and facial prominences. In order to understand the role of
      FGFs in vivo, we have analyzed the competency of head mesenchyme to respond to
      FGFs via expression of the high affinity receptors FGFR1, 2, and 3. Receptor
      transcripts, especially those of FGFR2 and FGFR3, were localized to specific
      regions of the head. We raise the possibilities of particular receptor-ligand
      combinations and the possible functions of these interactions in the
      morphogenesis of the head, face, and brain. Finally, we discuss the relationship
      between FGF receptor expression in the chicken and the phenotypes of FGF receptor
      mutations in humans.

PMID- 9286595
TI  - Paired-related murine homeobox gene expressed in the developing sclerotome,
      kidney, and nervous system.
AB  - We isolated a murine homeobox containing gene, Uncx4.1. The homeodomain sequence
      exhibits 88% identity to the unc-4 protein at the amino acid level. In situ
      hybridization analysis revealed that Uncx4.1 is expressed in the paraxial
      mesoderm, in the developing kidney, and central nervous system. The most
      intriguing expression domain is the somite, where it is confined to the caudal
      part of the newly formed somite and subsequently restricted to the caudal domain
      of the developing sclerotome. In the central nervous system, Uncx4.1 is detected
      in the developing spinal cord, hindbrain, mesencephalon, and telencephalon. The
      temporal and spatial expression pattern suggests that Uncx4.1 may play an
      important role in kidney development and in the differentiation of the sclerotome
      and the nervous system.

PMID- 9286596
TI  - Neovascularization of the Xenopus embryo.
AB  - The receptor tyrosine kinase, Flk-1 or VEGFR-2, and its ligand, vascular
      endothelial growth factor (VEGF) are required for the development of the
      embryonic vasculature. Targeted disruption of either gene in mice results in the
      failure of vascular system formation. The Xenopus homologues of flk-1 and VEGF
      have been cloned and their expression has been examined throughout early
      embryonic development. These studies indicate that flk-1 is expressed in groups
      of endothelial precursor cells which will form the major blood vessels of the
      embryo, including the posterior cardinal veins, the dorsal aorta, the vitelline
      veins, and the endocardium. VEGF expression is found in tissues adjacent to the
      mesenchyme containing the flk-1-expressing endothelial precursors. Expression of
      both flk-1 and VEGF is transient, appearing as the primary vascular plexus is
      forming and declining steadily after the onset of functional embryonic
      circulation. After establishment of the primary vascular structures, flk-1
      expression is also observed in the intersegmental veins which form by an
      angiogenic mechanism. Overall, these results support a role for VEGF/flk-1
      signaling in both vasculogenesis and angiogenesis in the Xenopus embryo. When
      VEGF is expressed ectopically in Xenopus embryos by microinjection of either
      plasmid DNA or synthetic mRNA, large, disorganized vascular structures are
      produced. This result indicates that ectopic VEGF is capable of altering the
      architecture of the developing vascular network.

PMID- 9286597
TI  - Metabolic and hormonal responses during repeated bouts of brief and intense
      exercise: effects of pre-exercise glucose ingestion.
AB  - We investigated metabolic and hormonal responses during repeated bouts of brief
      and intense exercise (a force-velocity test; Fv test) and examined the effect of
      glucose ingestion on these responses and on exercise performance. The test was
      performed twice by seven subjects [27 (2) years] according to a double-blind
      randomized crossover protocol. During the experimental trial (GLU), the subjects
      ingested 500 ml of glucose polymer solution containing 25 g glucose 15 min before
      starting the exercise. During the control trial (CON), the subjects received an
      equal volume of sweet placebo (aspartame). Exercise performance was assessed by
      calculating peak anaerobic power (W(an,peak)). Venous plasma lactate
      concentration increased significantly during the Fv test (P < 0.001), but no
      difference was found between CON and GLU. Blood glucose first decreased
      significantly from the beginning of exercise up to the 6-kg load (P < 0.001) and
      then increased significantly at W(an,peak) and for up to 10 min during the
      recovery period (P < 0.001) in both CON and GLU. Insulin concentrations decreased
      significantly in both groups, but were higher at W(an,peak) in GLU compared with
      CON (P < 0.05). Glucagon and epinephrine did not change significantly in either
      group, but epinephrine was significantly lower in GLU after glucose ingestion (P
      < 0.05) and at W(an,peak) (P < 0.05). W(an,peak) was not significantly different
      between CON and GLU. In conclusion, blood glucose and insulin concentrations
      decreased during repeated bouts of brief and intense exercise, while blood
      lactate concentration increased markedly without any significant change in
      glucagon and epinephrine concentrations. Glucose ingestion altered metabolic and
      hormonal responses during the Fv test, but the performance as measured by
      W(an,peak) was not changed.

PMID- 9286598
TI  - Beta-endorphin infusion alters pancreatic hormone and glucose levels during
      exercise in rats.
AB  - beta-Endorphin (BE) infusion at rest can influence insulin and glucagon levels
      and thus may affect glucose availability during exercise. To clarify the effect
      of BE on levels of insulin, glucagon and glucose during exercise, 72 untrained
      male Sprague-Dawley rats were infused i.v. with either: (1) BE (bolus 0.05 mg.kg
      1 + 0.05 mg.kg-1.h-1, n = 24); (2) naloxone (N, bolus 0.8 mg.kg-1 + 0.4 mg.kg-1,
      n = 24); or (3) volume-matched saline (S, n = 24). Six rats from each group were
      killed after 0, 60, 90 or 120 min of running at 22 m.min-1, at 0% gradient. BE
      infusion resulted in higher plasma glucose levels at 60 min [5.93 (0.32) mM] and
      90 min [4,16 (0.29) mM] of exercise compared to S [4.62 (0.27) and 3.41 (0.26 mM]
      and N [4.97 (0.38) and 3.44 (0.25) mM]. Insulin levels decreased to a greater
      extent with BE [21.5 (0.9) and 18.3 (0.6) uIU.ml-1] at 60 and 90 min compared to
      S [24.5 (0.5) and 20.6 (0.6) uIU.ml-1] and N [24.5 (0.4) and 21.6 (0.7) uIU.ml-1]
      groups. Plasma C-peptide declined to a greater extent at 60 and 90 min of
      exercise with BE infusion compared to both S and N. BE infusion increased
      glucagon at all times during exercise compared to S and N. These data suggest
      that BE infusion during exercise influences plasma glucose by augmenting glucagon
      levels and attenuating insulin release.

PMID- 9286599
TI  - Sensation of breathlessness and respiratory oxygen cost during cycle exercise
      with and without conscious entrainment of the breathing rhythm.
AB  - The conscious entrainment of respiratory rhythm to exercise rhythm (ENT) has been
      hypothesized to alleviate breathing discomfort and reduce the oxygen (O2) cost of
      ventilation with a resulting decrease in total O2 uptake (VO2) during rhythmic
      exercise. This hypothesis has been tested in the study reported here. Eight
      female subjects performed cycle exercise at 50 rpm under two work load conditions
      of 40% and 60% of maximal VO2. During a 30-min exercise period at each work load,
      each subject was asked to breathe under two conditions for 15 min each: (1)
      spontaneously (non-ENT run), and (2) deliberately entraining the breathing rhythm
      to the cycling rhythm at preferred coupling ratios of the two rhythms (ENT run).
      In the ENT run, most subjects chose a ratio of 1:2. In each run, pulmonary
      ventilation (VE), total VO2 and the breathlessness sensation (BS) were measured
      at 4-5 min. BS was assessed according to a Borg category scale. The remaining 10
      min of each 15-min run were allotted for measurement of the O2 cost of
      ventilation (delta VO2/delta VE), assessed by a hypercapnia-induced
      hyperventilation method in which the VO2 of the respiratory muscles (VO2RM) was
      calculated by multiplying delta VO2/delta VE by the prevailing VE. On average,
      there were no significant differences in any of the variables, VO2, delta
      VO2/delta VE, VO2RM and BS, between the non-ENT and ENT runs performed at any
      work load. However, there were wide variations among the subjects in the
      differences (delta) between the two runs, and significant correlations were found
      between delta VO2 vs delta VE, delta VO2 vs delta VO2RM, and delta BS vs delta
      VO2RM of individual subjects. These results indicate that reductions of the total
      VO2 and BS with ENT could occur in subjects in whom the VO2RM decreased during
      ENT.

PMID- 9286600
TI  - The longitudinal development of running economy in males and females aged between
      13 and 27 years: the Amsterdam Growth and Health Study.
AB  - The purpose of this study was to describe the longitudinal development of running
      economy [defined as the oxygen uptake (VO2) at a submaximal running speed] in
      males and females from teenage to young adult age using data from the Amsterdam
      Growth and Health Study. Submaximal VO2 (in ml.kg-1.min-1) was measured in 84
      males and 98 females while they ran on a treadmill at a constant speed of 8 km.h
      1 for 6 min at three different treadmill slopes (0%, 2.5% and 5%). This test was
      carried out six times, on the same subjects at the ages of 13, 14, 15, 16, 21,
      and 27 years. The longitudinal development of running economy in males and
      females was analysed using a two-way analysis of variance for repeated
      measurements. At all three slopes, a significant decrease in VO2 with increasing
      age was found for both males and females, implying a significant increase in
      running economy for both sexes. Males showed significantly higher VO2 values than
      females at all ages measured and for all three slopes, suggesting that females
      have a significantly higher running economy than males. In order to make a better
      comparison of the VO2 of individuals of different sizes, allometric models were
      used; power function ratios were constructed in which body mass was expressed to
      an exponential power. Following this analysis the difference in submaximal VO2
      and running economy between males and females appeared even larger.

PMID- 9286601
TI  - Ventilatory response at the onset of voluntary exercise and passive movement in
      endurance runners.
AB  - The present study was performed to examine whether or not the ventilatory
      response at the onset of voluntary exercise and passive movement in endurance
      runners is the same as in untrained subjects. Twelve long-distance runners
      belonging to the varsity athletic club and 13 untrained subjects of our
      university participated as subjects in this study. Maximum oxygen uptake was
      significantly higher in the endurance runner group [mean (SD) 70.8 (4.7) ml.kg
      1.min-1] than in the untrained group [49.8 (6.3) ml.kg-1.min-1].
      Cardiorespiratory responses during voluntary exercise and passive movement of
      alternate flexion-extension of the right and left legs for about 15 s at a
      frequency of about 60 rpm, were determined by means of breath-by-breath
      techniques. Minute inspiratory ventilation (VI), tidal volume (VT), respiratory
      frequency (fb), cardiac output (Qc), stroke volume (SV) and heart rate (HR)
      increased significantly immediately at the onset of voluntary exercise and
      passive movement. The incremental rate for VI was greater than that for Qc.
      Average values and standard deviations of changes in VI were calculated as the
      difference between the mean of the first and second breath and the mean of five
      breaths preceding the exercise or movement. The rates obtained in voluntary
      exercise and passive movement in the endurance runner group [2.34 (0.82) and 1.72
      (0.71 l.min-1), respectively] were significantly (P < 0.05) lower than those in
      the untrained group [4.16 (2.66) and 2.71 (1.56 l.min-1), respectively]. Also
      changes in VT and HR were significantly lower in the endurance group than in the
      untrained group with regard to both voluntary exercise and passive movement. The
      results suggest that the magnitude of cardiorespiratory responses at the onset of
      voluntary exercise and passive movement in humans is influenced by chronic
      endurance training for long periods.

PMID- 9286602
TI  - Effects of combined beta-adrenergic and cholinergic blockade on the initial
      ventilatory response to exercise in humans.
AB  - To elucidate whether combined adrenergic and parasympathetic blockade would
      affect the ventilatory response to exercise, especially at the initial stage
      (phase I), six healthy subjects performed a brief and light voluntary bilateral
      leg extension exercise and passive movements under the conditions of control
      (before the blockade) and after intravenous administration of combined beta
      adrenergic (propranolol, 0.2 mg.kg-1) and muscarinic (atropine, 0.04 mg.kg-1)
      receptor antagonists. The movements were continued only within two breaths after
      the onset of the motion. Ventilation increased immediately and significantly (P <
      0.05) within the first breath at the onset of voluntary exercise in all
      conditions as compared with at rest. However, the magnitude of increase in mean
      ventilation within two breaths at the start of exercise as against the resting
      value (delta ventilation) was significantly less (P < 0.05) after the combined
      blockades (2.5 l.min-1) than in the control condition (3.7 l.min-1). Passive
      movements showed a similar but smaller change as compared with voluntary
      exercise. The heart rate response to exercise was attenuated by the combined
      blockade while cardiac output showed a slight change at the onset of exercise. It
      is concluded that phase I should occur despite the inhibited activity of the beta
      adrenergic and the cholinergic systems; nevertheless, the response was attenuated
      by the combined blockade. These results suggest a possible role of the beta
      adrenergic and/or cholinergic systems in the rapid increase in ventilation that
      occurs at the start of exercise.

PMID- 9286603
TI  - Lumbar paraspinal muscle fatigability in repetitive isoinertial loading: EMG
      spectral indices, Borg scale and endurance time.
AB  - The purpose of this study was to develop a submaximal repetitive isoinertial back
      muscle endurance test by defining the relationships between the power spectral
      indices of paraspinal muscle electromyographic (EMG) activities, endurance time
      and a subjective estimate of fatigue (Borg scale). Bilateral surface EMG
      recordings were obtained over the lumbar paraspinal muscles in ten individuals
      who were currently free from back pain. All subjects performed repetitive upper
      trunk extensions (25 degrees flexion and 5 degrees extension, 30 repetitions per
      min), while movement below the third lumbar vertebral body was mechanically
      restricted. The load level depended upon upper body mass, sex, and age. The tests
      continued for as long as the subjects were able to maintain the required
      repetition rate (endurance time). Median (MF) and mean power frequency (MPF)
      slopes were calculated by performing a fast Fourier transformation after
      confirmation of EMG stationarity by recurrence quantification analysis. MF and
      MPF correlations with endurance time/Borg scale were measured for the first 60 s
      (0.60-0.88/0.42-0.86), the first 90 s (0.62-0.89/0.52-0.90), the first 120 s
      (0.50-0.76/0.41-0.73), and the entire repetitive run (0.63-0.88/0.54-0.90). To
      test for the reproducibility of the spectral indices EMGs were recorded for 2 min
      during repetitive loading from the same subjects on two consecutive days.
      Corresponding spectral slopes of MF and MPF were correlated at 60 s (0.36-0.93),
      90 s (0.58-0.92), and 120 s (0.70-0.94) at the L3-L4 and L5-S1 levels, indicating
      good reproducibility of results from alternate recording sessions at the L5-S1
      level. It is concluded that paraspinal muscle spectral indices (MF and MPF)
      measured before the onset of total muscle fatigue are good predictors of
      endurance time and are closely related to the subjective perception of fatigue.

PMID- 9286605
TI  - The effects of antagonist moment on the resultant knee joint moment during
      isokinetic testing of the knee extensors.
AB  - The purpose of this study was to examine the effects of moment of antagonistic
      muscle on the resultant joint moment during isokinetic eccentric and concentric
      efforts of the knee extensors. Ten males performed maximum eccentric and
      concentric knee extension and flexion efforts on a Biodex dynamometer at 0.52
      rad.s-1 (30 degrees.s-1). Electromyographic (EMG) activity of vastus medialis and
      biceps femoris (hamstrings) was also recorded. The antagonistic moment of the
      hamstrings was determined by recording the integrated EMG (iEMG)/ moment
      relationship at different levels of muscle effort. The iEMG/moment curves were
      fitted using second-degree polynomials. The polynomials were then used to predict
      the antagonistic moment exerted by the hamstrings from the antagonist iEMG. The
      antagonistic moment had a maximum of 42.92 Nm and 28.97 Nm under concentric and
      eccentric conditions respectively; paired t-tests indicated that this was a
      significant difference (P < 0.05). These results indicate that the resultant
      joint moment of knee extensors is the result of both agonist and antagonist
      muscle activation. The greater antagonist muscle activity under concentric
      activation conditions may be partly responsible for the lower resultant joint
      concentric moment of knee extensors compared with the corresponding eccentric
      activation. The antagonist moment significantly affects comparisons between the
      isokinetic moments and agonist EMG and in vitro force measurements under
      different testing (muscle action and angular velocity) conditions.

PMID- 9286604
TI  - Energy expenditure using isotope-labelled water (2H218O), exercise performance,
      skeletal muscle enzyme activities and plasma biochemical parameters in humans
      during 95 days of endurance exercise with inadequate energy intake.
AB  - Two men, R.F. and M.S., pulled sledges each with starting masses of 222 kg, 2300
      km across Antarctica. Exercise was performed for approximately 10 h each day for
      95 days. Despite an average energy intake of 21.3 MJ.day-1 both subjects lost
      more than 25% of body weight. Energy expenditure was measured using energy
      balance data (EB) and isotope-labelled water (2H218O). Isotope doses were taken
      on day 0 and day 50 of the expedition. During the first 50 days both methods gave
      reasonable agreement, giving energy expenditures of 38.3 (EB) and 35.5 (2H218O)
      MJ.day-1 in R.F. and 28.6 (EB) and 29.1 (2H218O) MJ.day-1 in M.S. The isotope
      data for days 20-30 yielded exceptional values of 44.6 MJ.day-1 in R.F. and 48.7
      MJ.day-1 in M.S. Estimates of energy expenditure between day 51 and day 96 were
      much lower and although the methods were in agreement for R.F.-24.1 (EB) and 23.1
      (2H218O) MJ. day-1, there was poor agreement for MS-26.8 (EB) and 18.8 (2H218O)
      MJ.day-1. However, some practical difficulties occurred during this second period
      and there were also problems arising from marked increases in body water that
      made estimates of body mass and composition change difficult to interpret. The
      latter problems were probably due to malnutrition, which may have also been
      responsible for surprising increases in urinary excretion of 2H and 18O observed
      in both men at around day 81. These increases may reflect the release of label
      incorporated into molecules other than water which do not normally freely
      exchange with the body water pool under the circumstances of marked
      malnourishment. Following the expedition, both men showed declines in maximal O2
      consumption (VO2max, 53.6 to 41.2 ml O2 kg-1.min-1 in R.F., 58.1-46.0 ml O2 kg
      1.min-1 in M.S.); maximal voluntary isometric force production in different
      muscle groups (up to 19.9% in R.F. and 55.8% in M.S.) and both cytoplasmic and
      mitochondrial skeletal muscle enzyme activities (up to 56% in R.F. and 63% in
      M.S.). Plasma samples taken during the expedition showed low glucose levels,
      inappropriately high insulin levels, and declines in testosterone and luteinizing
      hormone. Thyroxine, cholesterol, albumin and triglyceride levels remained normal.

PMID- 9286606
TI  - Accuracy of pulse oximetry during intense exercise under severe hypoxic
      conditions.
AB  - There is a growing need to measure arterial oxygen saturation with a non-invasive
      method during heavy exercise under severe hypoxic conditions. Although the
      accuracy of pulse oximetry has been challenged by several authors, it has not
      been done under extreme conditions. The purpose of this study was to evaluate the
      accuracy of a pulse oximeter (Satllite. Datex, Finland) during exercise under
      hypoxic conditions where arterial oxygen saturation was below 75%, simulating
      exercise at extreme altitude. Ten healthy non-smoking men performed two exercise
      studies of 30 min under normoxia and under hypoxia on two consecutive days. The
      exercise intensity was 80% of maximal O2 consumption of VO2max. Arterial oxygen
      saturation measured by pulse oximetry was corrected (SpO2[corr]) according to
      previously published equations and was compared to arterial oxygen saturation
      (SaO2) in blood samples taken simultaneously from the radial artery. Reference
      arterial saturation values ranged from 57.2 to 97.6% for the whole data set. This
      data set was split according to low (SaO2 < or = 75%) and high (SaO2 > 75%) SaO2
      values. The error of pulse oximetry (SpO2[corr]-SaO2) was 2.05 (0.87)% [mean
      (SD)] and 1.80 (1.81)% for high and low SaO2 values, respectively. SpO2[corr] and
      SaO2 were highly correlated (r = 0.93, SEE = 1.81) for low values. During high
      intensity constant workload under severe hypoxic conditions, once corrected,
      pulse oximetry provides an estimate of SaO2 with a mean error of 2%. Thus, the
      correction previously described for SpO2 values above 75% saturation applies also
      to SpO2 values in the range of 57-75% during exercise under hypoxic conditions.

PMID- 9286607
TI  - Effect of intensive swimming training on lung volumes, airway resistance and on
      the maximal expiratory flow-volume relationship in prepubertal girls.
AB  - The aim of the present study was to analyse the effect of 1 year of intensive
      swimming training on lung volumes, airway resistance and on the flow-volume
      relationship in prepubertal girls. Five girls [9.3 (0.5) years old] performing
      vigorous swimming training for 12 h a week were compared with a control group of
      11 girls [9.3 (0.5) years old] who participated in various sport activities for 2
      h per week. Static lung volumes, maximal expiratory flows (MEF) at 75, 50 and 25%
      of vital capacity, 1-s forced expiratory volume (FEV1.0) and airway resistance
      (R(aw)) were measured by means of conventional body plethysmograph techniques.
      Prior to the training period there were no significant differences between the
      two groups for any of the parameters studied. Moreover, for both groups, all
      parameters were within the normal range for children of the corresponding age.
      After 1 year of training, vital capacity (VC), total lung capacity (TLC) and
      functional residual capacity (FRC) were larger (P < 0.05) in the girl swimmers
      than in the control group, while physical development in terms of height and
      weight was similar. FEV1.0 (P < 0.01), MEF25, MEF50 (P < 0.05) and MEF75 as well
      as the ratio MEF50/TLC (P < 0.05) had increased in the girl swimmers but were
      unchanged in the control group. R(aw) tended to be lower in the girl swimmers and
      higher in the control group. The results indicate that intensive swimming
      training prepuberty enhances static and dynamic lung volumes and improves the
      conductive properties of both the large and the small airways. As to the
      causative mechanism, it can be speculated that at prepuberty intensive swimming
      training promotes isotropic lung growth by harmonizing the development of the
      airways and of alveolar lung spaces.

PMID- 9286608
TI  - Effect of increased physical activity on growth and differentiation of
      regenerating rat soleus muscle.
AB  - Our purpose was to determine the effect of physical exercise on growth and
      differentiation during regeneration of a slow-twitch muscle.
      Degeneration/regeneration of the left soleus muscles of Wistar female rats was
      induced by injection of a snake venom. Muscular differentiation was studied by
      monitoring the sequential expression of the various myosin heavy chain isoforms
      (MHCs). Rats were assigned to one of two groups: cage sedentary (n = 14) or
      exercised (n = 16). The exercise programme began 1-day post-injection and the
      rats ran 1 h/day on a motorized treadmill. Then, 9 and 25 days after venom
      treatment, the soleus MHC phenotype as determined by immunohistology,
      electrophoresis and immunoblotting, was studied. At 25 days the expression of
      MHCs by regenerating soleus was not changed by the increased level of physical
      activity (P > 0.05). Exercised and sedentary regenerating muscles contained
      similar numbers of type-I fibres (100% of total fibres), levels of MHC-1 (85.4
      and 89.5% of total MHCs), MHC-2a and M/HC-2x/d and their fibres expressed MHC-1
      (100% of total fibres) and MHC-2 (45-50%) in the same way. Moreover, the masses
      of regenerating and nonregenerating soleus were significantly increased by
      physical exercise (P < 0.02). At 9 days no effect of muscular exercise was found.
      In conclusion, endurance exercise did not alter differentiation of regenerating
      soleus. Moreover regenerating soleus can respond to increased physical activity
      by enhancing its mass in the same way as mature muscle.

PMID- 9286609
TI  - Changes in the plantaris muscle as an indicator of alterations in lean body mass
      of obese Zucker rats following prolonged energy restriction and subsequent
      partial recovery.
AB  - To study the effects of a prolonged (80 day), severe (64% body mass loss) energy
      restriction and subsequent refeeding on skeletal muscle tissue, specifically the
      plantaris muscle, 21 genetically obese Zucker rats were selected for this study.
      Six rats were initially killed and served as baseline (BASE), then 15 rats
      underwent severe energy restriction for 80 days. Seven of these restricted rats
      (RESTRICT) were then killed and assessed while the other eight rats (REHAB) were
      fed a dry rehabilitation diet that provided 100% of the recommended energy and
      1.5 times the recommended protein for growth. Once the REHAB rats had recovered
      approximately 45% of their original mass loss, these animals were then evaluated.
      Within 20 min after being killed, the plantaris muscles from each animal in each
      group had been removed, weighed, and frozen. Analyses included total plantaris
      mass, as well as differences in fiber diameters, esterase activity, and fiber
      type distributions between three groups (BASE, RESTRICT, and REHAB). The extreme
      body mass loss of 64% in genetically obese Zucker rats resulted in significant
      tissue weight loss and reduced fiber diameters in the plantaris muscle. Refeeding
      resulted in larger muscle fiber diameters that approached baseline values but an
      11% difference in muscle weight remained and may be due to a decreased fiber
      number. Esterase activity seemed to indicate an initial fat utilization for the
      RESTRICT group, followed by suppressed esterase activity in the REHAB group,
      suggesting increased fat storage. No significant differences were found in fiber
      type distribution between BASE, RESTRICT, or REHAB animals.

PMID- 9286610
TI  - Influence of plyometric training on the mechanical impedance of the human ankle
      joint.
AB  - The objective of this work was to study the effects of plyometric training on the
      mechanical properties of the ankle joint in humans. Changes in the mechanical
      parameters of this musculo-articular structure were quantified with the aid of a
      sinusoidal perturbation technique. This technique allowed the expression of the
      mechanical impedance of the musculo-articular system in terms of stiffness,
      viscosity and inertia. Measurements were performed under passive conditions and
      when the subject performed plantar flexion. A 7-week period of training induced a
      decrease in the slope of the relationship between stiffness and plantar flexion
      torque, whereas passive stiffness was increased. A slight decrease in viscosity
      and an invariability in inertia were also found. These results are interpreted in
      terms of the possible adaptations of the musculo-articular structure and
      ultrastructure involved in the performance of plantar flexion.

PMID- 9286611
TI  - Intra- and extracranial artery blood velocity during a sudden blood pressure
      decrease in humans.
AB  - The intra- and extracerebral Doppler artery blood velocity responses to a 10-mmHg
      abrupt blood pressure (BP) decrease in ten healthy men were studied. This
      decrease was obtained using two cuffs placed over both thighs. First, cuffs were
      inflated to pressures greater than the arterial BP for 5 min. Next, they were
      deflated to 60 mmHg in order to prevent venous return from the legs. We obtained
      a decrease in mean arterial BP of from 101 (10) to 90 (10) mmHg [mean (SD), P <
      0.01] without modifications in the heart rate [HR, 88 (14) beats min-1]. Middle
      cerebral artery mean blood velocity (MCAmv) decreased immediately from 50 (10) to
      42 (12) cm s-1 (P < 0.05). Simultaneously, temporal superficial artery mean blood
      velocity (TSAmv) decreased from 11 (3) to 7 (2) cm s-1 (P < 0.05) and common
      carotid artery blood flow (CCAbf) decreased from 305 (23) to 233 (33) ml min-1 (P
      < 0.05). After 5 s, MCAmv and CCAbf returned to baseline values, whereas TSAmv [8
      (2) cm s-1], mean arterial BP [86 (10) mmHg] remained low and HR increased [92
      (12) beats min-1]. TSAmv, BP and HR returned to baseline values in 1 min. These
      data confirm that cerebral blood flow (CBF) is very rapidly regulated but that
      blood flow in extracranial territories is not and that it follows the arterial BP
      changes.

PMID- 9286612
TI  - Effects of AMPA receptor positive modulators on amphetamine- and dizocilpine
      induced locomotion.
AB  - Two allosteric alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)
      receptor positive modulators, 1-(1,3-benzodioxol-5-ylcarbonyl)piperidine (1-BCP)
      and 1-(quinoxalin-6-ylcarbonyl)piperidine (CX516), and the antipsychotic drug,
      haloperidol, were tested for their ability to inhibit hyperactivity induced by
      amphetamine and dizocilpine in mice. Haloperidol (0.03-1.0 mg/kg) and 1-BCP (20.0
      120.0 mg/kg) attenuated hyperactivity induced by both amphetamine and
      dizocilpine, with higher potency against amphetamine. CX516 (30.0-170.0 mg/kg),
      however, failed to attenuate amphetamine- and dizocilpine-induced hyperactivity
      up to a dose which decreased spontaneous locomotor activity. These results
      indicate that AMPA receptor positive modulators may not be uniform with regard to
      their effects on dopamine-mediated behaviors and their antipsychotic potential.

PMID- 9286614
TI  - Prodystonic effects of riluzole in an animal model of idiopathic dystonia related
      to decreased total power in the red nucleus?
AB  - The effects of riluzole (2-amino-6-trifluoromethoxy benzothiazole) on the
      severity of dystonia were examined in mutant hamsters (dtsz), an animal model of
      idiopathic dystonia in which dystonic attacks can be age dependently induced by
      mild stress. Previous studies in hamsters have shown antidystonic activity of
      various glutamate receptor antagonists whereas lamotrigine, considered as an
      inhibitor of glutamate release, exerted prodystonic effects. The latter,
      unexpected, finding prompted us to investigate riluzole which is thought to
      possess antiglutamatergic properties with mechanisms similar to those of
      lamotrigine. Riluzole (2, 5, 10 or 20 mg/kg i.p.) dose dependently decreased the
      latency to onset of dystonic attacks. A dose of 10 or 20 mg/kg significantly
      increased the severity of dystonia. Even in dtsz hamsters older than 70 days,
      i.e., after spontaneous remission of age-dependent dystonia, riluzole (10 or 20
      mg/kg) provoked severe long-lasting (> 4 h) dystonic attacks. At a dose of 20
      mg/kg, riluzole provoked short-lasting (< 1 h) dystonic disturbances also in non
      dystonic control hamsters. Electroencephalographic recordings from depth
      electrodes in the red nucleus, where recent studies have shown abnormal neural
      activity before and during dystonic attacks in dtsz hamsters, revealed that
      riluzole (10 mg/kg) tended to cause a further decrease of the total power in dtsz
      hamsters and significantly reduced the total power in control animals. This
      finding may indicate that the prodystonic effects of riluzole are related to
      alterations of rubrospinal activity. With regard to antidystonic effects of
      glutamate receptor antagonists demonstrated in previous studies, the prodystonic
      effects of riluzole and, as shown by recent experiments, of lamotrigine also, may
      be due to the lack of selectivity of these drugs to inhibit glutamate release.

PMID- 9286613
TI  - Effects of Ca2+ and Na+ channel inhibitors in vitro and in global cerebral
      ischaemia in vivo.
AB  - In the present study we have examined the effects of the small organic molecules:
      NNC 09-0026 ((-)-trans-1-butyl-4-(4-dimethylaminophenyl)-3-[(4-trifluoromethyl-ph
      eno xy) methyl] piperidine dihydrochloride); SB 201823-A (4-[2-(3,4
      dichlorophenoxy)ethyl]-1-pentyl piperidine hydrochloride); NS 649 (2-amino-1-(2,5
      dimethoxyphenyl)-5-trifluoromethyl benzimidazole); CNS 1237 (N-acenaphthyl-N'-4
      methoxynaphth-1-yl guanidine) and riluzole on human omega-conotoxin sensitive N
      type voltage-dependent Ca2+ channel currents (ICa) expressed in HEK293 cells, on
      Na+ channel currents (INa) in acutely isolated cerebellar Purkinje neurones in
      vitro and in the gerbil model of global cerebral ischaemia in vivo. Estimated
      IC50 values for steady-state inhibition of ICa were as follows; NNC 09-0026, 1.1
      microM; CNS 1237, 4.2 microM; SB 201823-A, 11.2 microM; NS 649, 45.7 microM and
      riluzole, 233 microM. Estimated IC50 values for steady-state inhibition of Na+
      channel currents were as follows: NNC 09-0026, 9.8 microM; CNS 1237, 2.5 microM;
      SB 201823-A, 4.6 microM; NS 649, 36.7 microM and riluzole, 9.4 microM. In the
      gerbil model of global cerebral ischaemia the number of viable cells (mean +/-
      S.E.M.) per 1 mm of the CA1 was 215 +/- 7 (sham operated), 10 +/- 2 (ischaemic
      control), 44 +/- 15 (NNC 09-0026 30 mg/kg i.p.), 49 +/- 19 (CNS 1237 30 mg/kg
      i.p.), 11 +/- 2 (SB 201823-A 10 mg/kg i.p.), 17 +/- 4 (NS 649 50 mg/kg i.p.) and
      48 +/- 18 (riluzole 10 mg/kg i.p.). Thus NNC 09-0026, CNS 1237 and riluzole
      provided significant neuroprotection when administered prior to occlusion while
      SB 201823-A and NS 649 failed to protect. These results indicate that the Ca2+
      channel antagonists studied not only inhibited human N-type voltage-dependent
      Ca2+ channels but were also effective blockers of rat Na+ channels. Both NNC 09
      0026 and CNS 1237 showed good activity at both Ca2+ and Na+ channels and this may
      contribute to the observed neuroprotection.

PMID- 9286616
TI  - MK 801 reverses haloperidol-induced catalepsy from both striatal and
      extrastriatal sites in the rat brain.
AB  - The present study investigated whether the anticataleptic effect of (+)-5-methyl
      10,11-dihydro-5H-dibenzo(a,d)-cyclohepten-5,10-imine (MK 801) is due to a
      blockade of N-methyl-D-aspartate (NMDA) receptors in striatal output pathways as
      well as in the striatum. Catalepsy induced by haloperidol (1 mg/kg i.p.) was more
      effectively reversed by MK 801 (0.2 mg/kg i.p.) given 10 min prior to rather than
      45 min after the neuroleptic. Catalepsy evoked by intrastriatal haloperidol (7
      micrograms/side) was also strongly attenuated by systemic MK 801 (0.2 mg/kg
      i.p.). We also found that the cataleptic rigidity induced by systemic haloperidol
      (1 mg/kg i.p.) could be prevented by prior injection of MK 801 into the striatum
      (10 micrograms), subthalamic nucleus (5 micrograms), entopeduncular nucleus (5
      micrograms) or substantia nigra pars reticulata (1 microgram). These results
      suggest that the anticataleptic action of systemic MK 801 versus haloperidol, is
      due to the blockade of NMDA receptors in the striatum as well as in striatal
      output circuits through the subthalamus. However, systemic MK 801 (0.2 mg/kg
      i.p.) was without effect on the catalepsy elicited by injecting muscimol into the
      globus pallidus (25 ng) or ventromedial thalamus (50 ng). These findings suggest
      that MK 801 has little influence over thalamic excitatory feedback to the cortex,
      and that hypoactivity of the pallidum may not be a prerequisite for hyperactivity
      in the subthalamus.

PMID- 9286615
TI  - Evidence for a role of presynaptic AMPA receptors in the control of neuronal
      glutamate release in the rat forebrain.
AB  - The role of presynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      (AMPA) receptors in controlling the neuronal release of excitatory amino acids
      has been investigated. Stimulation of presynaptic AMPA receptors by the
      endogenous agonist L-glutamate, or by (R,S)-AMPA, dose-dependently enhanced the
      Ca(2+)-dependent, tetrodotoxin-insensitive, electrically-stimulated release of
      [3H]D-aspartate from rat forebrain slices. This AMPA receptor-mediated response
      showed marked stereoselectivity with the activity residing solely in the (S)
      isomer. (R)-AMPA was inactive in this respect. AMPA-evoked responses were
      significantly enhanced in the presence of the AMPA receptor desensitization
      inhibitor, cyclothiazide (10 microM). Moreover, responses to both AMPA and
      glutamate were inhibited by competitive (NBQX) and non-competitive (GYKI 52466)
      AMPA receptor-selective antagonists in a dose-dependent manner. These results
      provide strong support for the existence of presynaptic AMPA receptors acting to
      enhance the synaptic release of excitatory amino acids in the mammalian
      forebrain. Such a positive feedback system may play an important functional role
      in physiological (e.g., long-term potentiation) and/or pathological (e.g.,
      epileptogenesis) processes in the mammalian central nervous system. AMPA-type
      autoreceptors may provide new targets for drug action.

PMID- 9286618
TI  - Endothelium-dependent rhythmic contractions induced by cyclopiazonic acid in rat
      mesenteric artery.
AB  - The action of cyclopiazonic acid, the putative inhibitor of the Ca(2+)-ATPase of
      endoplasmic reticulum, on phenylephrine-evoked-isometric contractions in rat
      isolated mesenteric arteries were investigated. Cyclopiazonic acid (3 microM)
      induced an initial relaxation followed by rhythmic contractions of the
      phenylephrine-precontracted arteries with intact endothelium. Removal of
      endothelium abolished the effect of cyclopiazonic acid. Pretreatment of tissues
      with NG-nitro-L-arginine (100 microM) abolished the initial relaxation but not
      the rhythmic contractions. Indomethacin and glibenclamide did not affect the
      cyclopiazonic acid-induced response. Charybdotoxin (100 nM) converted the
      cyclopiazonic acid-induced rhythmic contractions to the sustained tension in the
      absence or presence of NG-nitro-L-arginine (100 microM). Pretreatment of
      charybdotoxin (100 nM) abolished cyclopiazonic acid-induced rhythmic activity but
      not the initial relaxation. Nifedipine (10 nM) abolished the effect of
      cyclopiazonic acid. Moderate increase of extracellular K+ (20 mM) reduced the
      initial relaxation but completely abolished rhythmic contractions induced by
      cyclopiazonic acid. The remaining relaxation was reversed or prevented by NG
      nitro-L-arginine (100 microM). The results of the present investigation indicate
      that cyclopiazonic acid caused endothelium-dependent response in rat isolated
      mesenteric arteries probably by releasing nitric oxide responsible for the
      initial relaxation, and probably by releasing endothelium-derived hyperpolarizing
      factors primarily responsible for activation of charybdotoxin-sensitive K+
      channels and induction of rhythmic contractile activity.

PMID- 9286617
TI  - PCCG-IV inhibits the induction of long-term potentiation in the dentate gyrus in
      vitro.
AB  - The effects of two ligands with previously established high and selective potency
      for metabotropic glutamate receptors (mGlu receptors) group II have been
      investigated on the high frequency stimulation (HFS) induced long-term
      potentiation of the field excitatory postsynaptic potential (EPSP) in the dentate
      gyrus of the rat hippocampus in vitro. The ligands investigated were
      (2S,1'S,2'S,3'R)-2-(2"-carboxy-3'-phenylcyclopropyl)glycine (PCCG-IV) and (R,S)
      alpha-methyl-4-tetrazolylphenylglycine (MTPG). PCCG-IV (10 microM) strongly
      inhibited the induction of long-term potentiation of the field EPSP by high
      frequency stimulation. MTPG (50 microM) did not inhibit the induction of long
      term potentiation, but prevented the inhibition of long-term potentiation
      induction by PCCG-IV. The inhibition of long-term potentiation induction by PCCG
      IV is suggested to be due to an agonistic action on mGlu receptor group II,
      probably mGlu3 receptor, as the inhibition of long-term potentiation can be
      reversed by the application of MTPG, a well-known selective and potent antagonist
      of mGlu receptor group II.

PMID- 9286619
TI  - Effects of the 5-HT1 receptor agonists, sumatriptan and CP 93,129, on dural
      arterial flow in the rat.
AB  - The blood flow in and around the medial meningeal artery (dural arterial flow)
      was recorded in the exposed parietal dura mater encephali of the anesthetized rat
      using laser Doppler flowmetry. Local electrical stimulation of the dura mater
      (pulses of 0.5 ms delivered at 7.5-17.5 V and 5 or 10 Hz for 30 s) caused
      temporary increases in dural arterial flow. The effects of the 5-HT1 receptor
      agonists sumatriptan and CP 93,129 on the basal flow and the electrically evoked
      increases in flow were examined. Topical administration of undiluted sumatriptan
      (12 mg/ml) lowered the basal and the evoked flow by 20% on average. Systemic
      (i.v.) administration of sumatriptan (0.24, 0.72 and 3.6 mumol/kg) caused a short
      lasting reduction of the evoked flow increases only at the higher doses while the
      basal flow was not significantly altered. Systemic administration of CP 93, 129
      (0.46 and 4.6 mumol/kg) caused no significant changes of the basal and the evoked
      flow. At a dose of 23 mumol/kg CP 93,129 lowered the basal flow by 20% and the
      evoked flow by 30% for 20 min. The systemic arterial pressure was not
      significantly altered by sumatriptan and CP 93,129 within the whole range of
      doses. It is suggested that sumatriptan and CP 93,129 at high doses exert
      inhibitory effects on those fine afferent nerve fibers which release the
      calcitonin gene-related peptide, since this neuropeptide mediates the evoked
      increases in dural arterial flow.

PMID- 9286620
TI  - Serotonergic effects of dotarizine in coronary artery and in oocytes expressing 5
      HT2 receptors.
AB  - In strips of pig coronary arteries incubated in oxygenated Krebs-bicarbonate
      solution at 37 degrees C, dotarizine blocked the phasic contractions evoked by 5
      HT (0.5 microM) or K+ depolarization (35 mM K+) with an IC50 of 0.22 and 3.7
      microM, respectively. Flunarizine inhibited both types of contractions with IC50
      values of 1.7 microM for 5-HT and 2.4 microM for K+ responses. In Xenopus oocytes
      injected with in vitro transcribed RNA encoding for 5-HT2A or 5-HT2C receptors, 5
      HT (100 nM for 20 s) applied every 10 min caused, in both cases, a reproducible
      inward current through Ca2(+)-activated Cl- channels (ICl). Dotarizine inhibited
      the 5-HT2A response in a concentration-dependent manner, with an IC50 of 2.2 nM.
      In contrast, the 5-HT2C response was unaffected by 1 microM dotarizine and
      blocked around 62% by 10 microM of this drug. The ICl activated either by
      intracellular injection of inositol 1,4,5-trisphosphate (IP3) in oocytes or by
      direct photorelease of Ca2+ in DM-nitrophen-injected oocytes was unaffected by 10
      microM dotarizine. It is concluded that dotarizine blocks 5-HT2A receptors with a
      high affinity; the compound is devoid of intracellular effects on any further
      steps of the transduction pathway (i.e., IP3 receptor). Contrary to flunarizine
      that blocks equally well the serotonergic and the K+ vascular responses,
      dotarizine exhibits 17-fold higher affinity for vascular 5-HT receptors. These
      findings might be relevant to an understanding of the mechanism involved in the
      use of dotarizine and flunarizine as prophylactic agents in migraine.

PMID- 9286621
TI  - Does nitric oxide contribute to the negative chronotropic and inotropic effects
      of endothelin-1 in the heart?
AB  - N omega-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, was
      used to examine whether nitric oxide was involved in the negative chronotropic
      and inotropic effects of endothelin-1 in the presence of isoprenaline in
      mammalian heart. In isolated rabbit right atria, endothelin-1 elicited a negative
      chronotropic effect in the presence of isoprenaline, which was associated with a
      decrease in the isoprenaline-induced accumulation of cyclic AMP. On the other
      hand, in the dog ventricular trabeculae, the negative inotropic effect of
      endothelin-1 was not accompanied by a significant reduction in the isoprenaline
      induced accumulation of cyclic AMP. N omega-nitro-L-arginine methyl ester
      affected neither the negative chronotropic effect nor the negative inotropic
      effect of endothelin-1. The effects of endothelin-1 on the isoprenaline-induced
      cyclic AMP accumulation were not influenced by N omega-nitro-L-arginine methyl
      ester either. These results indicate that the negative chronotropic and inotropic
      effects of endothelin-1 in the presence of isoprenaline in mammalian cardiac
      muscle do not involve the nitric oxide-mediated signaling pathway.

PMID- 9286622
TI  - Effect of 5-HT1A receptor agonist, 8-OH-DPAT, on cough responses in the conscious
      guinea pig.
AB  - We have studied the role for 5-hydroxytryptamine (5-HT) in the modulation of the
      cough reflex by examining the effect of a selective 5-HT1A receptor agonist, 8
      hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on cough and respiratory rate
      in conscious guinea pigs. Animals were placed in a box and exposed to the tussive
      agent citric acid (0.5 M) for 10 min, 3 min after terbutaline (0.05 mg/kg i.p.)
      was administered to prevent bronchoconstriction. 8-OH-DPAT inhibited at low doses
      (0.008 and 0.016 mg/kg) but potentiated at high doses (0.25 and 0.5 mg/kg) the
      citric acid-induced number of coughs, but dose-dependently increased respiratory
      rate. Methysergide (0.05-5 mg/kg), a 5HT1 and 5HT2 receptor antagonist, and
      ketanserin (0.005 mg/kg), a 5HT2 receptor antagonist, had no effects on cough or
      respiratory rate. Methysergide inhibited the increased cough responses and
      respiratory rate induced by 8-OH-DPAT at high doses, while ketanserin was without
      effect. These results suggest that 8-OH-DPAT may induce both in inhibition and
      activation of the cough reflex, the latter involving central 5HT1-receptor
      activation.

PMID- 9286623
TI  - Effect of amylin in various experimental models of gastric ulcer.
AB  - Subcutaneous administration of amylin (20-40 micrograms/kg) prevented, in a dose
      dependent manner, reserpine- and serotonin-induced gastric damage, but the anti
      ulcer effect was not present when lesions were induced by pylorus ligation. The
      protective effect of amylin was inhibited by pretreatment with capsicin as well
      as CGRP-(8-37), a calcitonin gene-related peptide (CGRP) and amylin receptor
      antagonist, and was significantly reduced by domperidone, a dopamine D2 receptor
      antagonist, or neostigmine, an inhibitor of acetylcholinesterase. Our data
      suggest that the gastroprotective activity of amylin in some experimental models
      of gastric ulcers involves capsaicin-sensitive fibers and CGRP receptors.
      Moreover, the peptide interferes, at least in part, with the dopaminergic and
      parasympathetic systems.

PMID- 9286624
TI  - Chronic treatment with BRL 35135 potentiates the action of insulin on lipid
      metabolism.
AB  - The effects of a beta 3-adrenoceptor agonist on insulin-induced changes in lipid
      metabolism were studied in obese male Zucker (fa/fa) rats during euglycaemic
      clamp. Rats were treated with BRL 35135 (R*, R*-(+/-)-methyl-4-[2-[2-hydroxy-2-(3
      chlorophenyl)-ethyl-amino]-propyl] phenoxyacetate hydrobromide) (0.5 mg/kg per
      day in drinking water) for three weeks before an euglycaemic hyperinsulinaemic
      clamp was performed. Insulin infusion lowered serum non-esterified fatty acids
      and plasma glycerol more efficiently in BRL 35135-treated than in control rats
      although plasma insulin remained significantly lower in the BRL 35135-treated
      than in the control rats during the clamp. In conclusion, chronic treatment with
      BRL 35135 potentiates the effect of insulin on lipid metabolism.

PMID- 9286625
TI  - Competitive and non-competitive inhibition of L-3, 4-dihydroxyphenylalanine
      uptake in Opossum kidney cells.
AB  - The present study aimed to determine the kinetics of L-3,4-dihydroxyphenylalanine
      (L-DOPA) uptake in Opossum kidney (OK) cells and to define the type of inhibition
      produced by L-5-hydroxytryptophan (L-5-HTP), cyanine 863 and 3,3'
      diethyloxacarbocyanine (3,3'-DOC). Non-linear analysis of the saturation curves
      revealed for L-DOPA a Km (in microM) of 129 (114, 145) and a Vmax (in nmol/mg
      protein per 6 min) of 30.0 +/- 0.4 IC50 values for L-5-HTP (1454 microM) obtained
      in the presence of a nearly saturating (250 microM) concentration of L-DOPA were
      almost 4-fold those obtained when non-saturating (25 microM) concentrations of L
      DOPA were used (330). IC50 values for cyanine 863 and 3,3'-DOC (638 and 353
      microM) obtained in the presence of a nearly saturating (250 microM)
      concentration of L-DOPA were similar to those obtained when non-saturating (25
      microM) concentrations of L-DOPA were used (654 and 339 microM). Vmax values (in
      nmol/mg protein per 6 min) for L-DOPA uptake were identical in the absence (36.4
      +/- 0.7) and the presence of L-5-HTP (39.2 +/- 1.3), but Km values (microM) were
      significantly greater (P < 0.05) when L-DOPA uptake was studied in the presence
      of L-5-HTP (121 (100, 142) versus 318 (237, 399)). In contrast, the effect of
      cyanine 863 and 3,3'-DOC was to cause a significant reduction in Vmax values
      without significant changes in Km values. It is concluded that L-5-HTP exerts a
      competitive type of inhibition of L-DOPA uptake in cultured OK cells, whereas
      both cyanine 863, an organic cation transport inhibitor and 3,3'-DOC behave as
      non-competitive inhibitors.

PMID- 9286626
TI  - [3H]GBR 12935 binding in platelets: a possible association with cytochrome P
      450IID6?
AB  - The nature of [3H] (1-[2-(diphenylmethoxy)ethyl)-4-(3-phenylpropyl) piperazine
      dihydrochloride) (GBR 12935) binding to human platelets was investigated. A
      common property of the inhibitors of this binding was their association with the
      cytochrome P-450 system. cis-Flupenthixol and (1-[2-[bis(4
      fluorophenyl)methoxy]ethyl]-4-[3-phenylpropyl) piperazine dihydrochloride) (GBR
      12909) biphasically inhibited the binding. The fraction of [3H]GBR 12935 binding
      that was inhibited by low concentrations of cis-flupenthixol was sensitive to
      protease treatment. [3H]GBR 12935 binding in this fraction was saturable and of
      high affinity (Kd 4.5 nM). The present results reveal that [3H]GBR 12935 binds to
      multiple sites in platelets and suggest that part of the binding is associated
      with cytochrome P-450IID6.

PMID- 9286627
TI  - Immunomodulatory responses to delta-opioid receptor ligands in human lymphocytes.
AB  - In phytohemagglutinin (PHA) activated human peripheral blood mononuclear cells.
      [3H]thymidine uptake and interferon gamma production were increased by the delta
      opioid receptor agonist, deltorphin-I (10(-14)-10(-10) M) and by the delta-opioid
      antagonist naltrindole (10(-13)-10(-9) M). Combination of 10-9 M naltrindole with
      deltrophin-I (10(-12)-10(-8)M) significantly inhibited the proliferative response
      but did not affect interferon production.

PMID- 9286628
TI  - Affective disorders following stroke.
AB  - Numerous studies in stroke patients suggest that the left frontal anterior region
      may be strategic for depression. However, these findings could not always be
      replicated. Some authors even deny any etiological contribution of lesion
      location to depression. The predominant role of the right hemisphere in secondary
      mania is well recognized. In disorders such as apathy, anxiety, catastrophe
      reactions and pathological laughing and crying, further studies are needed to
      determine the potential clinico-topographic correlations. Affective disorders are
      important to consider in stroke patients, since they may influence neurological
      recovery and may be responsive to treatment. Remarkable features of emotional
      behavior, such as disinhibition, denial, indifference, overt sadness and
      aggressiveness, are not rare during the acute phase of stroke and might be
      overlooked if not searched for systematically with appropriately designed scales.
      Some of these early behaviors, such as denial, may relate to the late development
      of depression, anxiety and other disorders. Systematic studies on large samples
      of patients may allow to establish which of these acute emotional behavioral
      changes are markers for the delayed development of mood disorders.

PMID- 9286629
TI  - Transcranial magnetic stimulation in patients with cerebellar stroke.
AB  - Conduction time of the central motor pathways (CMCT) by transcranial magnetic
      stimulation (TMS) was performed within the first two weeks in 7 patients with
      isolated hemicerebellar lesions after stroke. Cerebellar infarcts were small (< 2
      cm in diameter) in 5 patients and no brainstem structure was involved in CT
      studies. The threshold (3 cases) and CMCT (4 cases) were abnormal or asymmetric
      by stimulation of the motor cortex contralateral to the impaired hemicerebellum.
      The follow-up study in 2 patients revealed electrophysiological improvement
      closely related to clinical cerebellar recovery rate. CMCT was significantly
      longer by cortex stimulation contralateral to the impaired hemicerebellum than by
      ipsilateral stimulation. Prolonged CMCT was significantly correlated with the
      rated severity of cerebellar signs. Increased threshold may be due to depressed
      facilitating action of the deep cerebellar nuclei on contralateral motor cortex.
      Abnormal CMCT might result in reduced size and increased dispersion of the
      efferent volleys. Recovery of electrophysiological results could represent in
      part true potentially reversible functional deficit. Whichever the
      pathophysiological mechanisms involved, our results demonstrate that the
      cerebellum dysfunction plays a role in the abnormalities of CMCT elicited by TMS.

PMID- 9286630
TI  - Possible regulation of intracranial pressure by human atrial natriuretic peptide
      in cerebrospinal fluid.
AB  - To clarify the function of human atrial natriuretic peptide (hANP) in the
      cerebrospinal fluid (CSF), we examined hANP levels in the CSF of patients with
      various neurological diseases. The subjects were 16 controls without neurological
      disease and 45 patients with neurological disease. The 45 patients with
      neurological disease were divided into a group of 15 patients with intracranial
      hypertension (IH) and a group of 30 patients with normal pressure (NP). hANP in
      both CSF (1-hANP) and serum (s-hANP) was measured by RIA. Patients with IH were
      followed up. We analyzed correlations between 1-hANP and other parameters of CSF.
      Increase in concentration of 1-hANP was positively correlated with intracranial
      pressure (ICP; r = 0.72; p < 0.01), but not with other CSF parameters or with s
      hANP. The concentration of 1-hANP appeared to be increased especially over a
      threshold value of ICP. In a followup study of patients with IH, changes in 1
      hANP paralleled changes in ICP in every case (r = 0.79; p < 0.01). Our findings
      strongly suggest that 1-hANP plays an important role in the regulation of ICP in
      humans.

PMID- 9286631
TI  - Pyogenic infectious spondylitis: clinical, laboratory and MRI features.
AB  - Pyogenic infectious spondylitis (PIS) is an uncommon but serious inflammatory
      disorder of the discovertebral junction with frequent involvement of neural
      structures including the spinal cord. We report a series of 41 patients (age
      range 21-75 years, mean age 59 years) with primary PIS confirmed by signal
      abnormality of the intervertebral disk and adjacent vertebral bodies on magnetic
      resonance imaging. The prevailing clinical symptom was focal back pain aggravated
      by percussion in 90% of patients. Radicular signs or symptoms were present in 59%
      and spinal cord symptoms in 29% of patients, respectively. Evidence of
      inflammation consisted of an elevated sedimentation rate in 76%, leukocytosis in
      61% and fever in 61% of individuals. Predisposing factors such as diabetes
      mellitus, previous nonspinal surgery and other sites of infection or inflammation
      were identified in 17 (41%) patients and 30 (73%) were older than 50 years. The
      lumbar spine was most often affected and PIS was associated with an epidural
      abscess in 15 (37%) patients. Increased alertness for PIS in the context of focal
      back pain with clinical or laboratory signs of inflammation is needed to speed up
      its detection.

PMID- 9286633
TI  - Progressive hemiparesis in frontal lobe degeneration.
AB  - Hemiparesis has rarely been observed in frontal lobe degeneration (FLD). We
      describe the clinical, neuropsychological and neuroimaging findings of a patient
      in whom a slowly evolving hemiparesis was the principal symptom of FLD, and of 2
      demented patients in whom hemiparesis was an early and prominent symptom. The
      occurrence of central motor deficits in FLD is reviewed, and a synopsis of the
      differential diagnosis of hemiparesis in neurodegenerative diseases is given.

PMID- 9286632
TI  - CYP2D6 polymorphism is not associated with essential tremor.
AB  - Recent reports have shown an association between cytochrome P450IID6 (CYP2D6)
      polymorphism and Parkinson's disease. We investigated the association between
      this polymorphism and the risk for developing essential tremor (ET). Leukocytic
      DNA from 91 unrelated ET patients and a control group of 258 unrelated healthy
      individuals was studied for the occurrence of eight different CYP2D6 allelic
      variants by using allele-specific PCR amplification Xbal and EcoRI-RFLP's
      analyses. The prevalence for these allelic variants in the ET and control groups
      were, respectively: CYP2D6*1 76.9 and 78.7%, CYP2D6*2 0.5 and 0.2%, CYP2D6*3 0
      and 1%, CYP2D6*4 12.1 and 12.2%, CYP2D6*5 1.6 and 1.7%, CYP2D6*9 4.4 and 2.9%,
      CYP2D6*2x2 4.4 and 3.2%. The prevalence of subjects with absent CYP2D6 activity
      (those carrying two defect genes) was 1.1 and 3.1% in ET and control groups,
      respectively. Both groups studied were in Hardy-Weinberg equilibrium. These
      results indicate that mutations at the CYP2D6 gene do not seem to be a major
      factor in determining susceptibility to ET, and reinforces the view that ET and
      parkinsonism are distinct conditions.

PMID- 9286634
TI  - Patterns of muscle activity in legs in sleep apnea patients before and during
      nCPAP therapy.
AB  - Nocturnal muscle activity in legs (MAL) was studied in 19 patients with sleep
      apnea syndrome before and during nCPAP. We distinguished periodic (P-MAL) and
      nonperiodic (N-MAL) as well as apnea-associated and independent MALs. N-MALs were
      strongly associated with apneas and disappeared during nasal continuous positive
      airway pressure (nCPAP). P-MALs showed a rather long intermovement interval (IMI)
      of about 54 s when associated with respiratory disturbances and a shorter one of
      about 38 s when occurring independently. In 5 patients with predominantly
      independent P-MALs and a short IMI before and during nCPAP an incidental
      coexistence of sleep apnea with periodic leg movements in sleep syndrome (PLMS)
      was postulated. Five patients with an equal number of apnea-associated and
      independent MALs before nCPAP had a long IMI which shortened under nCPAP, while
      the majority of MALs become independent. This could indicate a facilitating or an
      unmasking effect of nCPAP on PLMS. Four patients with predominantly apnea
      associated MALs with a long IMI before nCPAP showed an unchanged MAL pattern
      under nCPAP, despite the disappearance of apneas. Since some arousals persisted
      in these patients, insufficient nCPAP pressure with an upper airway resistance
      syndrome was suspected. We conclude that when P-MALs persist under nCPAP therapy
      a long IMI may indicate an upper airway resistance syndrome, whereas a short IMI
      may indicate a coexisting or even induced PLMS.

PMID- 9286635
TI  - Different effects of levodopa and apomorphine on blink reflex recovery cycle in
      essential blepharospasm.
AB  - With the aim of assessing dopaminergic responsiveness in essential blepharospasm,
      we investigated the effects of oral levodopa and subcutaneous apomorphine on
      blink reflex recovery cycle in 7 blepharospasm patients. We found that in
      blepharospasm the excitability of the blink reflex recovery cycle was increased
      compared with control subjects. The oral administration of levodopa/carbidopa
      (500/50 mg) did not significantly modify the blink reflex recovery cycle. The 50
      micrograms/kg dose of apomorphine decreased the amplitude of conditioned
      responses at 300 and 500 ms, whereas the 10 micrograms/kg dose was ineffective.
      We conclude that the excitability of the blink reflex recovery cycle in
      blepharospasm is partly under dopaminergic control. The partial normalization of
      the blink reflex recovery cycle excitability observed with 50 micrograms/kg
      apomorphine is consistent with the reported clinical efficacy of the drug in this
      condition.

PMID- 9286636
TI  - Ictal speech arrest and parasagittal lesions.
AB  - Lesions in the parasagittal region may cause seizures with speech arrest. To
      correlate lesion localization within the parasagittal region with ictal speech
      function we studied 11 patients with parasagittal lesions. The exact lesion
      localization was assessed with magnetic resonance imaging. In all patients with
      speech arrest the lesion involved the left superior frontal gyrus (n = 6), in 3
      patients the lesion was confined to this gyrus. Speech arrest did not occur in
      patients with right-sided lesions (n = 4) or left-sided lesions outside the
      superior frontal gyrus (n = 1). Our data suggest that a small lesion confined to
      the left superior frontal gyrus (the supplementary motor area) is sufficient to
      cause speech arrest.

PMID- 9286637
TI  - Hyperprolactinemia--an unusual initial manifestation of multiple sclerosis.

PMID- 9286638
TI  - Central nervous system involvement in Guillain-Barre-like syndrome: clinical and
      magnetic resonance imaging evidence.

PMID- 9286639
TI  - Carbamazepine-phenprocoumon interaction.

PMID- 9286640
TI  - Essential palatal tremor successfully treated with flunarizine.

PMID- 9286641
TI  - Long-term follow-up after open perineal cryotherapy in patients with locally
      confined prostate cancer.
AB  - OBJECTIVE: Appropriate therapies for locally confined adenocarcinoma of the
      prostate are available-but there is as yet no gold standard of therapy. For that
      reason, old therapeutic regimens are being revised. One such regimen is
      cryotherapy. METHODS: Between 1976 and 1989, 1,250 patients were seen with newly
      diagnosed prostate cancer. Sixty-six patients of stages T1c (n = 3), T2a (n =
      32), T2b (n = 9), T2c (n = 11), T3a (n = 4), T3b (n = 5) and T3c (n = 2) were
      treated by open perineal cryotherapy. Mean age was 68 years. Three months after
      surgery, transurethral resection of the prostate and/or perineal biopsy was
      performed. RESULTS: In 66% of patients with stages T1c-T2b and in 87% of patients
      with stages T2c-T3c, positive biopsies were obtained. To date, 28 patients have
      died between 3 and 16 years after cryotherapy, with a mean survival of 7.2 years.
      The mean follow-up period of survivors (38 patients) is 8.5 years. Complications
      were: stress-incontinence in 10%, impotence in 10% and temporary rectoperineal
      fistula in 8%. CONCLUSIONS: Cryosurgery is an effective treatment for locally
      confined prostate cancer. With improvement of the procedure, clinical outcome may
      also improve.

PMID- 9286642
TI  - A multicenter study on the detection of prostate cancer by digital rectal
      examination and prostate-specific antigen in men with or without urinary
      symptoms. Cooperative Group for Diagnosis of Prostate Cancer.
AB  - OBJECTIVE: The use of prostate-specific antigen (PSA) for prostatic cancer
      screening and the practical utility of the concept of PSA density are
      controversial. The aim this multicenter study was to assess the usefulness of PSA
      as a diagnostic procedure for prostate cancer in patients with urinary symptoms,
      and compare it with digital rectal examination (DRE). METHODS: We performed a
      multicenter study in 18 hospitals to assess the value of PSA in the diagnosis of
      prostate cancer. 2,054 outpatients, aged above 50 years, were included in the
      study. Patients with suspected prostatitis or severe systemic disease were
      excluded. PSA levels were measured in all patients (IMx) and a DRE was also
      performed. Patients with PSA levels > 3 ng/ml and/or a suspicious DRE underwent
      transrectal ultrasound and a prostate biopsy. RESULTS: PSA levels > 3 ng/ml
      and/or a suspect DRE were found in 680 (33%) patients, in 587 (29%) of whom a
      biopsy was performed. A cancer of the prostate was diagnosed in 131 patients. The
      cancer detection rate was 5.89% for PSA > 4 ng/ml, 4.38% for DRE and 6.37% for
      the combination of both methods. The combination of PSA and DRE allows for
      increasing the diagnostic sensitivity which would be achieved with either test
      alone. CONCLUSION: We recommended the use of PSA and DRE in combination as a
      diagnostic procedure for prostate cancer, since these are complementary methods
      which allow for detecting a population at a high risk of suffering prostate
      cancer.

PMID- 9286643
TI  - Comparison of digital rectal examination, transrectal ultrasonography, and
      multicoil magnetic resonance imaging for preoperative evaluation of prostate
      cancer.
AB  - OBJECTIVE: A prospective study was designed to compare the potentials of digital
      rectal examination (DRE), transrectal ultrasound (TRUS), and magnetic resonance
      imaging (MRI) using integrated endorectal and pelvic phased-array coils for
      preoperative estimation of tumor volume and local extent of prostate cancer.
      METHODS: Evaluation of 20 consecutive patients undergoing radical retropubic
      prostatectomy included DRE, TRUS with a 7.5-MHz transducer, and MRI on a 1.5
      tesla GE Signa system. Step sections (5 mm) of the entire specimen were
      performed, and tumor volume and percentage of gland involved were calculated.
      RESULTS: DRE, TRUS, and endorectal and pelvic phased-array MRI showed 50, 75, and
      95% of the cancers, respectively. There was a linear correlation on MRI between
      predicted tumor volume and pathological tumor volume (r = 0.82, p < 0.0001), but
      not between predicted volume on DRE or TRUS and real volume. The accuracy for
      detecting extracapsular penetration was 60% for DRE and TRUS and 79% for MRI. The
      accuracy for detecting seminal vesicle invasion was 60% for DRE, 66 for TRUS, and
      89% for MRI. The negative predictive value for extracapsular and seminal vesicle
      extension was highest for MRI (85 and 93%, respectively). The accuracy for tumor
      location in the apex of the prostate was 30% for DRE, 47 for TRUS, and 89% for
      MRI. CONCLUSIONS: MRI with integrated endorectal and pelvic phased-array coils
      satisfactorily predicted tumor volume and tumor extent preoperatively. Multicoil
      MRI can assist in decision making as it is valuable in the definition of patients
      that may benefit from surgery and can be of help for evaluating the risk of a
      positive margin, especially in the apical resection.

PMID- 9286644
TI  - Transrectal ultrasonography in prostatic cancer: interexaminer variability of
      interpretation.
AB  - OBJECTIVE: To compare the variability of transrectal ultrasonographic (TRUS)
      interpretation for the decision of performing biopsies and the lesions to biopsy.
      METHODS: We extracted at random from our videotape database 16 records of
      patients who had undergone biopsies, added 2 normal glands and duplicated 2 of
      these 18 records. Based on the records, 5 well-trained physicians had to describe
      the images on the tape, and to decide whether or not to biopsy the prostate. A
      kappa test was computed between each couple of readers, and for the whole group.
      The kappa test denotes the agreement between examiners. A value of kappa < 0.20
      is considered poor to slight agreement, 0.2-0.40 is considered fair agreement.
      RESULTS: The agreement between the 5 readers was poor for the biopsy decision
      (kappa < 0.2) and the difficulty to read the records (kappa = 0.05). The results
      with the global kappa were similar with a highest value < 0.3. Most of the
      abnormalities were described in the peripheral zone. The global kappa for the
      seminal vesicles interpretation is poor, but better for the capsular penetration.
      CONCLUSION: TRUS has a poor informative value between different practitioners.
      This poor agreement between different practitioners must lead to more objective
      ultrasonographic methods.

PMID- 9286645
TI  - Results of rebiopsy for suspected prostate cancer in symptomatic men with
      elevated PSA levels.
AB  - AIM OF THE STUDY: To develop indications for repeat biopsy in patients with
      suspected prostate cancer and first negative biopsy. MATERIALS AND METHODS: 148
      consecutive patients, submitted to two or more biopsies for suspected prostate
      cancer, were extracted from our database on prostatic diseases. Patients were
      stratified according to the results of the last biopsy (benign or carcinoma)
      considering the results of the first and of the last biopsy when more than two
      biopsies had been performed. PSA velocity was calculated when the interval
      between PSA obtained before the initial and the final biopsy was at least 6
      months; PSA velocities were annualized and absolute changes between the two
      groups were analyzed. RESULTS: Prostatic carcinoma was detected in 60 of the 148
      patients (40.5%), including 19 of 41 (46.4%) with prostatic intraepithelial
      neoplasia (PIN) and 45 of 107 (42.1%) with normal tissue or prostatic epithelial
      atrophia on initial biopsy. 20% of patients (4 of 20) with low-grade PIN and
      71.1% (15 of 21) with high-grade PIN had cancer at repeat biopsy. The mean PSA
      value of patients with carcinoma on the repeat biopsy was higher than that of
      patients without carcinoma (13.3 vs. 10.7 ng/ml). However, this difference was
      not statistically significant (p = 0.37). Mean PSA velocity increased for
      patients with a final diagnosis of carcinoma versus those without evidence of
      carcinoma (+0.3 vs. +1.4 ng/ml/year); this difference was statistically
      significant (p = 0.002). CONCLUSIONS: According to these results, patients with
      either PIN II-III, or high PSA and PIN I on initial biopsy, and/or with elevated
      PSA velocity (more than 1 ng/ml/year) should undergo repeat prostate needle
      biopsy, being at high risk of prostate carcinoma.

PMID- 9286647
TI  - A study on the feasibility of vesicomyotomy in patients with motor urge
      incontinence.
AB  - OBJECTIVE: To study the feasibility of bladder autoaugmentation in patients with
      motor urge incontinence. PATIENTS AND METHODS: The clinical and urodynamic data
      of 5 patients were analyzed before and after treatment. All patients suffered
      from unstable bladders with a variable bladder capacity. All patients had
      urodynamic evaluation after 3 months. RESULTS: Three months after
      autoaugmentation 1 patient was continent while 4 were still incontinent. The
      continent patient had a stable bladder, whereas the others still suffered from
      unstable bladder contractions despite increased bladder capacity and leak point
      pressure. CONCLUSION: We did not succeed in abolishing bladder instability.
      Although our experience is limited, we cannot recommend vesicomyotomy as a
      routine procedure for motor urge incontinence at this time.

PMID- 9286646
TI  - Indications for preoperative seminal vesicle biopsies in staging of clinically
      localized prostatic cancer.
AB  - OBJECTIVE: To identify patients at high risk of extraprostatic seminal vesicle
      infiltration, in whom preoperative seminal vesicle biopsies should be performed.
      MATERIALS AND METHODS: We studied the relationship between extraprostatic seminal
      vesicle infiltration and the available preoperative data [age, clinical stage,
      prostate-specific antigen (PSA) level, number and site of positive prostatic
      sextant biopsies, Gleason score] in a total of 75 patients suffering from
      clinically localized prostatic adenocarcinoma who were candidates for radical
      prostatectomy. RESULTS: The chi 2 test showed that the preoperative data most
      significantly correlated with extraprostatic seminal vesicle infiltration were
      the presence of positive basal biopsies (p < 0.001). The PSA level did not have
      any predictive value. The most discriminant preoperative parameter of the state
      of the seminal vesicles (analysis of variance on a univariate model) was the
      state of the basal prostatic biopsies. The importance of this parameter was
      confirmed by cluster analysis. Overall, the risk of extraprostatic seminal
      vesicle invasion was 0 (0/21 patients) when the 2 basal prostatic biopsies were
      negative, 10.25% (4/39 patients) when 1 of the 2 basal prostatic biopsies was
      positive and 73.33% (11/15 patients) when both basal prostatic biopsies were
      positive. CONCLUSIONS: In a patient with clinically localized prostatic
      adenocarcinoma who is a candidate for radical prostatectomy, seminal vesicle
      biopsies are useless when basal prostatic biopsies are negative, regardless of
      the state of other preoperative parameters. When 1 or 2 basal prostatic biopsies
      are positive, seminal vesicle biopsies can improve the pretreatment pathological
      staging.

PMID- 9286648
TI  - Suspended pubovaginal fascial sling for the correction of complicated stress
      urinary incontinence.
AB  - OBJECTIVES: Our experience with a modification of the pubovaginal fascial sling
      technique for the treatment of complicated stress urinary incontinence is
      reviewed. METHODS: 20 women with complicated stress urinary incontinence
      underwent suspended pubovaginal fascial sling procedure, with which the sling
      tension is balanced by combining it with No. 1 Prolene suspension sutures placed
      at the bladder neck. RESULTS: With a mean follow-up period of 30.7 months, 18/20
      patients (90%) were cured of stress incontinence and 2 (10%) were improved.
      Postoperative complications were minimal, and the voiding dysfunction rate
      following surgery was 5%. CONCLUSIONS: With a relatively short follow-up we found
      the suspended pubovaginal fascial sling to be highly successful in the treatment
      of complicated stress urinary incontinence, with minimal voiding dysfunction and
      a low complication rate.

PMID- 9286649
TI  - Renal angiomyolipoma--experience of 20 years in Taiwan.
AB  - OBJECTIVE: 32 cases of renal angiomyolipoma were presented. Diagnosis, treatment
      and prognosis of the 32 cases were discussed. MATERIAL AND METHODS: A total of 32
      cases of renal angiomyolipoma treated at the Veterans General Hospital-Taipei
      between 1974 and 1994 were retrospectively reviewed. Follow-up periods ranged
      from 2 to 108 months (mean 43.4). RESULTS: Of the 32 cases, 26 were female, 28
      were unilateral lesions and 2 were associated with tuberous sclerosis. The tumor
      size averaged 6.73 cm (range 2-25). The mean age was 48.3 years. There was a
      typical image finding in 87.5% of the 28 unilateral tumors. Tumors larger than 4
      cm had a greater incidence of symptoms (90%) and a higher nephrectomy rate
      (18/22). 30 cases underwent surgery including 22 nephrectomy, 1 partial
      nephrectomy and 7 enucleation. The nephrectomy rate decreased from 90% (9/10) to
      59.1% (13/22) after 1985. Only 1 patient had a contralateral recurrence 26 months
      after surgery. Two cases had unusual presentations, which were perirenal capsule
      invasion and renal vein extension, respectively. CONCLUSIONS: Our experience with
      angiomyolipoma in the past 20 years showed that the advancement of imaging
      technology has much improved the diagnosis of this tumor. A correct diagnosis is
      possible in most cases before surgery. The nephrectomy rate has markedly
      decreased in recent years. Every effort should be made to preserve renal tissue
      in the treatment of this benign tumor.

PMID- 9286650
TI  - Is the diet of patients with interstitial cystitis related to their disease?
AB  - OBJECTIVE: The dietary habits of interstitial cystitis (IC) patients compared to
      the average food and fluid consumption of the general population were evaluated
      and any spontaneous preference or avoidance of specific foodstuffs and fluids of
      IC patients was investigated. METHODS: A verbal interview with 16 IC patients
      provided information on the consumption of foodstuffs and fluids as well as
      dietary habits. Prior to the dietary interview none of the IC patients were aware
      of any possible dietary measures in relation to their IC symptoms. The results
      were compared to the averages of the general population. RESULTS: IC patients
      consumed statistically significantly less calories and fat (p < 0.05), and
      statistically significantly more fibers (p < 0.01) than the general population.
      Among the IC patients there were significantly fewer consumers of coffee (p <
      0.01) and significantly more consumers of (herbal) tea (p < 0.05). The difference
      in orange juice consumption was not significant. CONCLUSIONS: According to
      general standards, IC patients had a more healthy daily diet than the general
      population. The observation that IC patients consumed less coffee (caffeine) than
      the general population is consistent with previous reports on irritative IC
      symptoms exacerbating after caffeine consumption. No rationale for other dietary
      or fluid intake changes was found.

PMID- 9286651
TI  - Pharmacodynamics of intracavernously injected drugs and cavernous wall
      resistance.
AB  - OBJECTIVE: It was our aim to investigate whether drug transfer from the cavernous
      bodies to the systemic circulation after intracavernous (i.c.) injection is
      influenced by the resistance of the cavernous wall. METHODS: i.c. injection of
      62.5 micrograms digoxin as a tracer. (1) In 32 volunteers; in 5 together with the
      vasocontractor norepinephrine, in 20 together with a 'trimix' of vasodilators, in
      7 alone without vasoactive drug. Plasma digoxin levels were measured after 5, 10
      and 15 min. (2) Together with a trimix of vasodilators, in 30 men presenting a
      normal cavernosometry and in 30 men presenting an abnormal one. Plasma digoxin
      levels were measured after 2, 3, 5, 6, 10 and 15 min. RESULTS: (1) One minute
      after i.c. injection, the plasma peak of digoxin was 40 times higher (p < 0.01)
      after injection with norepinephrine than after injection with vasodilators. (2)
      There was a statistically significantly (p < 0.01) higher plasma digoxin level 5,
      6, 10 and 15 min after injection in the 30 patients presenting an abnormal
      cavernosometry than in the 30 patients presenting a normal one. CONCLUSIONS: Drug
      transfer from the cavernous bodies to the systemic circulation is highly
      influenced by the resistance of the cavernous wall. It seems possible to diagnose
      cavernous leakage by means of a peripheral dosage of a routinely dosable drug,
      injected i.c. together with vasodilators.

PMID- 9286652
TI  - Local interferon-alpha 2b is not an effective treatment in early-stage Peyronie's
      disease.
AB  - OBJECTIVE: Peyronie's disease is characterized by an acquired penile deviation
      that may lead to severe penile deformity. It is refractory to most conservative
      therapy, and surgical correction is therefore the treatment of choice once the
      disease process has come to a halt. Basic science, as well as our first clinical
      results on the use of interferons (IFNs), have been promising, suggesting a
      beneficial effect in the early noncalcified disease stage. MATERIAL AND METHODS:
      From July 1994 to October 1995, 30 patients suffering from early Peyronie's
      disease were treated with three local injections of 3 million units of IFN-alpha
      2b each into the plaque(s). The interval between the injections was 1 week.
      Patients were assessed clinically and ultrasonographically 6 months after the
      last injection. RESULTS: Peyronie's disease clinically improved in only 1 case,
      remained stable in 26 patients and worsened in 3. In 7 patients, a total of 10
      plaques at different sites were detected. By ultrasonography the treated plaques
      now showed calcifications in 3 cases, remained unchanged in 26 and could not be
      detected in 1 case. Of the 10 new plaques, 2 showed calcifications. Side effects
      (myalgia, fever) were considerable; in 74 of 90 injections, fever > 38 degrees C
      occurred, and a total of 8 working days were lost. CONCLUSION: IFN-alpha 2b,
      given according to our regimen, is not useful for the treatment of Peyronie's
      disease in the early stage since the disease progress continues at different
      sites in about 25% of the patients, and the side effects are untolerable. Our
      results also demonstrate that local therapy is not indicated in Peyronie's
      disease.

PMID- 9286653
TI  - Surgical management of retroperitoneal tumors with vena caval thrombus in the
      inferior cava using cardiopulmonary bypass, arrested circulation and profound
      hypothermia.
AB  - OBJECTIVE: It was our aim to review our surgical experience with retroperitoneal
      tumors extending to the vena cava by using cardiopulmonary bypass, deep
      hypothermia and circulatory arrest. METHOD: We performed this procedure in 15
      patients. The ages ranged between 16 and 70 years. The primary malignancies were
      renal cell carcinoma (n = 13), Wilms' tumor (n = 1) and paratesticular
      rhabdomyosarcoma (n = 1). RESULTS: There were no operative deaths. One patient
      died on the fourth postoperative day because of pulmonary embolization. The most
      common postoperative complications were: 1 patient required surgical
      reexploration because of hemorrhage, there was transitory renal failure in 3
      patients, 1 patient developed a postoperative reactive psychosis and 1 patient
      developed a subclinical pericarditis. CONCLUSION: We believe that the resection
      of retroperitoneal malignancies with venous tumor thrombus extension offers, in
      selected patients, the only chance of reasonable long-term survival. The
      application of a cardiopulmonary bypass and hypothermia in high level vena cava
      thrombi is an important advance that has improved the safety and technical
      efficacy of a difficult surgical undertaking.

PMID- 9286654
TI  - Study of the effects of thermotherapy in benign prostatic hypertrophy.
AB  - Prostatic transurethral thermotherapy was evaluated clinically using the
      Prostcare microwave system of the Bruker Company, which uses a microwave
      radiometer to measure and control intraprostatic temperature. OBJECTIVES: The aim
      of our study was to evaluate the immediate histological lesions induced in the
      prostatic tissue depending on the temperatures delivered to the prostate; the
      histological changes when adenectomy is carried out after thermotherapy, and the
      endoscopic appearance of the prostatic fossa 48 h, and 1, 2, 3 and 6 months after
      thermotherapy. METHODS: Our study was divided into three stages: in the first
      stage, we conducted thermotherapy in 10 patients in whom suprapubic adenectomy
      was indicated. During thermotherapy, a multipoint fiber-optic receptor and two
      thermocouples were implanted into the prostage gland at a distance of 5-15 mm
      from the urethra. Adenectomy was carried out 10 min after thermotherapy; the
      second stage of our study concerned the changes seen over time. We heated
      adenomas using the same protocol and carried out adenectomy 24, 48, 72 h, and 1
      week, 6 weeks and 3 months after thermotherapy, and lastly, we studied the
      endoscopic appearance after a single heating-session of 30 min by endoscopic
      controls at different times after thermotherapy (48 h, 1, 2, 3 and 6 months after
      thermotherapy). RESULTS: Macroscopic appearance: necrotic lesions measured 30 mm
      in length on average. Necrosis was roughly circumferential. Immediate
      histological aspect: in all cases, histological examination showed coagulation
      necrosis with periurethral thromboses. Histological changes: at 8 days, necrosis
      intensity was maximal and histological structures were difficult to identify.
      Endoscopic appearance: 3 months after thermotherapy, the typical endoscopic
      appearance was a large periurethral cavity. There was a sharp demarcation between
      untreated areas and cicatricial tissue. CONCLUSION: The efficacy of thermotherapy
      depends on the radiometric temperature, which should reach 47 degrees C (i.e. a
      temperature of 55-65 degrees C delivered to the prostate), and a rapid increase
      in temperature, i.e. in the power applied, which should reach the thermal
      radiometric level of 47 degrees C in 5 min. As soon as necrosis is obtained, the
      power is automatically reduced. Using this protocol, heating proves effective in
      30 min.

PMID- 9286655
TI  - Autogenous skin graft in the treatment of large incisional lumbar hernias and
      bulges.
AB  - OBJECTIVE: Repair of large incisional lumbar hernias or muscular bulges is a
      challenge to the surgeon as reflected by the high recurrence rate. We evaluated a
      surgical procedure using a running strip of autogenous skin graft as a retention
      suture. METHODS: Eight patients with large incisional lumbar hernias (> or = 20
      cm, n = 6) or muscular bulges (n = 2) underwent a parietal reconstruction with
      this procedure. Two patients had previously been treated with synthetic meshes
      without success, and one had a colocutaneous fistula. RESULTS: No recurrence was
      observed in 6 patients (75%) with a mean follow-up of 14 months. After
      significant weight gain, 2 repairs failed at 6 months and 1 year (partially in 1
      case). No recurrence was noted for muscular bulges. CONCLUSION: The use of a
      running strip of autogenous skin graft is a simple and reliable procedure for the
      repair of large lumbar hernias or muscular bulges for patients with stable weight
      conditions.

PMID- 9286656
TI  - The urological fate of young adults with myelomeningocele: a three decade follow
      up study.
AB  - OBJECTIVE: Virtually all patients with myelomeningocele suffer from neurogenic
      disorder of the bladder. Problems with incontinence are common and there is also
      a risk of deterioration of renal function. The aim of the present study was to
      determine the long-term urological fate of this patient group. PATIENTS AND
      METHODS: Twelve young adults with myelomeningocele were interviewed and their
      records reviewed. RESULTS: The patients started clean intermittent
      catheterization (CIC) at the age of 10-21 years. Three patients underwent
      urological surgery prior to the start of CIC. This was also the case for 3
      patients after having started CIC. Only 1 patient is completely continent. In the
      rest, the degree of incontinence varies. With few exceptions, the glomerular
      filtration rate was well preserved. Six of the incontinent patients had, on at
      least one occasion, denied incontinence to his doctor. CONCLUSION: It seems that
      the prognosis is good as far as renal function is concerned. However, continence
      is a prerequisite for good social adjustment. An obstacle for a rational
      treatment of incontinence, in the adolescent patient group, is the patient's
      strong tendency to underreport the actual incontinence situation. Thus, every
      effort must be made in order to obtain a correct history. In patients with
      validated incontinence, an aggressive treatment policy, including surgical
      intervention, is justified.

PMID- 9286657
TI  - Aspects of adult satisfaction with the result of surgery for hypospadias
      performed in childhood.
AB  - OBJECTIVES: Our aim was to ascertain whether the short-term results and the
      frequency of complications of corrective surgery in hypospadias correlate with
      patients' opinions on their sexual life and voiding ability as adults, as well as
      to establish what kind of problems underlie dissatisfaction with the result of
      surgery. METHODS: Between 1963 and 1975, 64 hypospadias patients, had been
      operated and their treatment completed in the Division of Paediatric Surgery at
      Tampere University Hospital. Their patient records were analyzed retrospectively,
      and a detailed questionnaire was mailed to 61 of them. RESULTS: 43 (70.5%)
      patients returned the questionnaire. Of the respondees, 62.8% expressed
      satisfaction with the result of the operation. Among those who were satisfied,
      22.2% had had complications after the operation, whereas 57.1% of those
      expressing dissatisfaction with the result had had complications (p < 0.05).
      Satisfied subjects had fewer problems in voiding and erection than those who were
      unsatisfied. They were also more often satisfied with the appearance of their
      penis and their sexual life. Fifteen patients would have preferred a longer
      follow-up. CONCLUSIONS: There is a correlation between the frequency of
      complications following hypospadias surgery and long-term results. Good short
      term results also predict good long-term ones. There is no straight correlation
      between the presence of voiding abnormalities and overall satisfaction with the
      result. It seems that the overall appearance as perceived by the patient and
      patients' satisfaction with their sexual function are more important. This study
      shows that the 1-stage methods currently used, represented here by the Mathieu
      technique, give superior results compared to older methods, at least partly
      because complications occur less often.

PMID- 9286658
TI  - Diagnostic value of natural fill cystometry in neurogenic bladder in children.
AB  - OBJECTIVE: Investigation of the diagnostic value of natural fill cystometry (NFC)
      in children with neurogenic bladder in comparison to conventional videocystometry
      (CVC). METHODS: We investigated 20 children (aged 6-11; 15 girls and 5 boys) with
      the following diagnoses: 6 myelomeningocele, 2 tethered cord syndrome, 1
      syringomyelia, 1 Vater syndrome, 1 suprasacral spinal cord injury, 9 suspected
      neurogenic bladder. We carried out a NFC after completing standard diagnostic
      including a slow-filling CVC. RESULTS: All investigations were completed
      successfully. The investigation lasted 6-20.5 h (mean 11:15 h). We registered
      phases of sleep, waking consciousness and micturition. CVC findings were
      confirmed in 45%: normal bladder function was confirmed in 2 patients (10%),
      bladder hyperactivity was confirmed in 7 patients (35%). In 55% we obtained
      different findings on NFC in comparison to the slow-filling CVC: bladder
      hyperactivity was not confirmed in 2 (10%), detection of bladder hyperactivity
      was found in 4 children (20%) with normal bladder function on CVC, detection of
      bladder hyperactivity on NFC was found in 5 children (25%) with low-compliance
      bladder on CVC. In 45% of all children, NFC detected new findings compared with
      CVC diagnoses. In 10%, possible artifacts (e.g. due to catheterization) of CVC
      were recognized. CVC findings were confirmed in 45%. CONCLUSION: These results
      are preliminary but they suggest that this is a new diagnostic method for
      improving the diagnostic standard in the childhood neurogenic bladder.

PMID- 9286659
TI  - p53 expression compared with other prognostic factors in OMS grade-I stage-Ta
      transitional cell carcinoma of the bladder.
AB  - OBJECTIVE: Recent studies have investigated the possibility that p53 protein and
      some macroscopic tumoral features, such as diameter and focality of the lesion,
      play a significant prognostic role in bladder cancer progression. A retrospective
      study was conducted on papillary grade-I stage-Ta transitional cell carcinoma
      (TCC) of the bladder. METHODS: p53 expression was evaluated using the
      immunohistochemical method. A group of 31 patients with papillary grade-I and
      stage-Ta TCC of the bladder with no recurrence or who recurred with no
      histological grading and staging variation in a 4-year mean follow-up period was
      compared with 28 grade-I and stage-Ta papillary TCC patients who underwent
      recurrences and a worsening in histological grading (grade II or grade III) or
      staging (T1) within the same period of time. The aim of this study was to
      investigate the hypothesis that altered patterns of expression of the protein
      products of the mutated p53 tumor-suppressor gene, when independently evaluated
      in comparison with other tumoral prognostic factors, are associated with tumor
      recurrence and progression in patients with Ta papillary grade-I TCC of the
      bladder. RESULTS: Our data show that when a p53 threshold of > 0% was considered,
      53.6% of patients with tumor progression in the follow-up period were p53
      positive compared with only 16.1% of the nonprogressing group (chi 2 = 6, p =
      0.02). On the contrary, p53 failed to show any value in predicting progression
      when a 5% threshold was considered (chi 2 = 1.12, p = 0.92). The multifocality of
      the tumoral lesion and recurrent tumor was highly predictive of tumor progression
      for both variables (chi 2 = 5.16, p = 0.003, and chi 2 = 0.23, p = 0.006,
      respectively). Multivariate analysis revealed p53 nuclear overexpression (at a
      threshold of > 0%) to be a single valuable prognostic factor of progression (OR =
      10.20, p = 0.009) and recurrence (OR = 54.19, p = 0.01). CONCLUSIONS: Our results
      lead to the conclusion that p53 immunohistochemical detection has no prognostic
      value in predicting tumoral relapse or progression of TaGI TCC of the bladder
      when a 5% positivity threshold is considered. On the contrary, when a p53 nuclear
      labelling of > 0% is considered as positive staining, this tumor marker becomes
      highly predictive of tumor recurrence and progression. These findings seem
      therefore to suggest the use of a slight p53 positivity (> 0%) as a valid tool in
      predicting the clinical behavior of TaGI bladder TCC. The prognostic impact of a
      multifocal lesion and a recurrent tumor as markers of progression is also
      confirmed by these results.

PMID- 9286660
TI  - Cytokeratin-19 fragment (CYFRA 21-1) in bladder cancer.
AB  - The present study was designed to evaluate the role of the cytokeratin-19
      fragment (CYFRA 21-1) as a tumor marker in bladder cancer. The bladder cancer
      cell line JMSU1 was used in the preclinical study. Subjects comprised 120 healthy
      volunteers, 20 patients with benign bladder diseases including acute cystitis and
      bladder stones, 12 patients with chronic renal failure, and 117 patients with
      histologically confirmed primary bladder cancer. CYFRA 21-1 concentrations were
      measured by a sandwich enzyme-linked immunosorbent assay. The preclinical study
      in vitro and in vivo showed that JMSU1 produced and released CYFRA 21-1 in the
      culture supernants and serum of JMSU1-bearing nude mice. The cutoff level was set
      at 3.5 ng/ml (mean + 3 SD) by the analysis in the healthy volunteers. Under this
      condition, sensitivity was 0% in benign bladder diseases, 83% in chronic renal
      failure, and 41.9% in bladder cancer. Serum CYFRA 21-1 levels increased
      significantly as tumor stage advanced or tumor grade increased. A serial follow
      up study demonstrated that patients with progressive showed a gradual increase in
      serum CYFRA 21-1 levels while patients who responded to the treatments had a
      marked decrease in serum CYFRA 21-1 levels. Higher serum CYFRA 21-1 levels were
      related to poor survival. The present study suggest that serum CYFRA 21-1 is a
      useful marker to monitor the clinical course of bladder cancer and to provide
      prognostic information.

PMID- 9286661
TI  - Evaluation of optimal stent size after antegrade endopyelotomy: an experimental
      study in the porcine model.
AB  - OBJECTIVES: To investigate the influence of two sizes of internal ureteral
      stents, 7 F and 12 F, on ureteropelvic junction (UPJ) healing after antegrade
      endopyelotomy. METHODS: A right UPJ stricture was created in 10 pigs using an
      open surgical retroperitoneal approach. This model of obstruction consists of
      initially bridging the UPJ with a Terumo guide wire through an upper third
      ureterotomy and securing two 2.0 chronic gut ties around the UPJ over the guide
      wire and a 6 F ureteral catheter. The ureteral catheter is then withdrawn and the
      guide wire left in situ coiled up within the lumbar wall and fixed to the
      urogenital opening. Eight days later, each UPJ stricture was incised
      percutaneously using the invagination technique. Five pigs received a 7 F double
      pigtail ureteral stent, while the remaining 5 pigs received a 12/7 F internal
      endopyelotomy stent. These stents were removed 1 week later. Retrograde
      ureteropyelography was performed at three months and the UPJ were examined
      grossly and harvested for histologic studies. RESULTS: One of the 5 pigs in each
      study group developed a recurrent stricture. The two groups were not
      statistically different in terms of histologic findings, although fibrosis of the
      muscle layer was more pronounced in the 12 F group. CONCLUSION: The use of a
      large caliber stent after experimental antegrade endopyelotomy does not provide
      any advantage over the use of a smaller easily positioned 7 F stent.

PMID- 9286662
TI  - Inflammatory pseudotumor of the epididymis.
AB  - We report the case of a 73-year-old patient who presented clinically with a
      palpable left scrotal mass after a 3-month history of therapy-resistant
      epidiymitis. He underwent epidiymectomy, and the following histopathologic and
      immunohistochemical evaluation revealed an inflammatory pseudotumor. We present
      the second case of an inflammatory pseudotumor of the epididymis being reported
      in the literature and give a brief review of the literature concerning this very
      rare neoplastic entity.

PMID- 9286663
TI  - Birth defects, Jimson weeds and bell curves.

PMID- 9286664
TI  - Genetic evidence that recognition of cosQ, the signal for termination of phage
      lambda DNA packaging, depends on the extent of head filling.
AB  - Packaging a phage lambda chromosome involves cutting the chromosome from a
      concatemer and translocating the DNA into a prohead. The cutting site, cos,
      consists of three subsites: cosN, the nicking site; cosB, a site required for
      packaging initiation; and cosQ a site required for termination of packaging. cosB
      contains three binding sites (R sequences) for gpNu1, the small subunit of
      terminase. Because cosQ has sequence identity to the R sequences, it has been
      proposed that cosQ is also recognized by gpNu1. Suppressors of cosB mutations
      were unable to suppress a cosQ point mutation. Suppressors of a cosQ mutation
      (cosQ1) were isolated and found to be of three sorts, the first affecting a base
      pair in cosQ. The second type of cosQ suppression involved increasing the length
      of the phage chromosome to a length near to the maximum capacity of the head
      shell. A third class of suppressors were missense mutations in gene B, which
      encodes the portal protein of the virion. It is speculated that increasing DNA
      length and altering the portal protein may reduce the rate of translocation,
      thereby increasing the efficiency of recognition of the mutant cosQ. None of the
      cosQ suppressors was able to suppress cosB mutations. Because cosQ and cosB
      mutations are suppressed by very different types of suppressors, it is concluded
      that cosQ and the R sequences of cosB are recognized by different DNA-binding
      determinants.

PMID- 9286666
TI  - Genetic interactions between HOP1, RED1 and MEK1 suggest that MEK1 regulates
      assembly of axial element components during meiosis in the yeast Saccharomyces
      cerevisiae.
AB  - During meiosis, axial elements are generated by the condensation of sister
      chromatids along a protein core as precursors to the formation of the
      synaptonemal complex (SC). Functional axial elements are essential for wild-type
      levels of recombination and proper reductional segregation at meiosis I. Genetic
      and cytological data suggest that three meiosis-specific genes, HOP1, RED1 and
      MEK1, are involved in axial element formation in the yeast Saccharomyces
      cerevisiae. HOP1 and RED1 encode structural components of axial elements while
      MEK1 encodes a putative protein kinase. Using a partially functional allele of
      MEK1, new genetic interactions have been found between HOP1, RED1 and MEK1.
      Overexpression of HOP1 partially suppresses the spore inviability and
      recombination defects of mek1-974; in contrast, overexpression of RED1
      exacerbates the mek1-974 spore inviability. Co-overexpression of HOP1 and RED1 in
      mek1-974 diploids alleviates the negative effect of overexpressing RED1 alone.
      Red1p/Red1p as well as Hop1p/Red1p interactions have been reconstituted in two
      hybrid experiments. Our results suggest a model whereby Mek1 kinase activity
      controls axial element assembly by regulating the affinity with which Hop1p and
      Red1p interact with each other.

PMID- 9286665
TI  - Mating in Saccharomyces cerevisiae: the role of the pheromone signal transduction
      pathway in the chemotropic response to pheromone.
AB  - The mating process in yeast has two distinct aspects. One is the induction and
      activation of proteins required for cell fusion in response to a pheromone
      signal; the other is chemotropism, i.e., detection of a pheromone gradient and
      construction of a fusion site available to the signaling cell. To determine
      whether components of the signal transduction pathway necessary for
      transcriptional activation also play a role in chemotropism, we examined strains
      with null mutations in components of the signal transduction pathway for diploid
      formation, prezygote formation and the chemotropic process of mating partner
      discrimination when transcription was induced downstream of the mutation. Cells
      mutant for components of the mitogen-activated protein (MAP) kinase cascade
      (ste5, ste20, ste11, ste7 or fus3 kss1) formed diploids at a frequency 1% that of
      the wild-type control, but formed prezygotes as efficiently as the wild-type
      control and showed good mating partner discrimination, suggesting that the MAP
      kinase cascade is not essential for chemotropism. In contrast, cells mutant for
      the receptor (ste2) or the beta or gamma subunit (ste4 and ste18) of the G
      protein were extremely defective in both diploid and prezygote formation and
      discriminated poorly between signaling and nonsignaling mating partners, implying
      that these components are important for chemotropism.

PMID- 9286667
TI  - Characterization of synthetic-lethal mutants reveals a role for the Saccharomyces
      cerevisiae guanine-nucleotide exchange factor Cdc24p in vacuole function and Na+
      tolerance.
AB  - Cdc24p is the guanine-nucleotide exchange factor for the Cdc42p GTPase, which
      controls cell polarity in Saccharomyces cerevisiae. To identify new genes that
      may affect cell polarity, we characterized six UV-induced csl (CDC24 synthetic
      lethal) mutants that exhibited synthetic-lethality with cdc24-4ls at 23 degrees.
      Five mutants were not complemented by plasmid-borne CDC42, RSR1, BUD5, BEM1,
      BEM2, BEM3 or CLA4 genes, which are known to play a role in cell polarity. The
      csl3 mutant displayed phenotypes similar to those observed with calcium
      sensitive, Pet- vna mutants defective in vacuole function. CSL5 was allelic to
      VMA5, the vacuolar H(+)-ATPase subunit C, and one third of csl5 cdc24-4ls cells
      were elongated or had misshapen buds. A cdc24-4ls delta vma5::LEU2 double mutant
      did not exhibit synthetic lethality, suggesting that the csl5/vma5 cdc24-4ls
      synthetic-lethality was not simply due to altered vacuole function. The cdc24-4ls
      mutant, like delta vma5::LEU2 and csl3 mutants, was sensitive to high levels of
      Ca2+ as well as Na+ in the growth media, which did not appear to be a result of a
      fragile cell wall because the phenotypes were not remedied by 1 M sorbitol. Our
      results indicated that Cdc24p was required in one V-ATPase mutant and another
      mutant affecting vacuole morphology, and also implicated Cdc24p in Na+ tolerance.

PMID- 9286669
TI  - Probing novel elements for protein splicing in the yeast Vma1 protozyme: a study
      of replacement mutagenesis and intragenic suppression.
AB  - Protein splicing is a compelling chemical reaction in which two proteins are
      produced posttranslationally from a single precursor polypeptide by excision of
      the internal protein segment and ligation of the flanking regions. This unique
      autocatalytic reaction was first discovered in the yeast Vma1p protozyme where
      the 50-kD site-specific endonuclease (VDE) is excised from the 120-kD precursor
      containing the N- and G-terminal regions of the catalytic subunit of the vacuolar
      H(+)-ATPase. In this work, we randomized the conserved valine triplet residues
      three amino acids upstream of the C-terminal splicing junction in the Vma1
      protozyme and found that these site-specific random mutations interfere with
      normal protein splicing to different extents. Intragenic suppressor analysis has
      revealed that this particular hydrophobic triplet preceding the C-terminal
      splicing junction genetically interacts with three hydrophobic residues preceding
      the N-terminal splicing junction. This is the first evidence showing that the N
      terminal portion of the V-ATPase subunit is involved in protein splicing. Our
      genetic evidence is consistent with a structural model that correctly aligns two
      parallel beta-strands ascribed to the triplets. This model delineates spatial
      interactions between the two conserved regions both residing upstream of the
      splicing junctions.

PMID- 9286668
TI  - The Cak1p protein kinase is required at G1/S and G2/M in the budding yeast cell
      cycle.
AB  - The CAK1 gene encodes the major CDK-activating kinase (CAK) in budding yeast and
      is required for activation of Cdc28p for cell cycle progression from G2 to M
      phase. Here we describe the isolation of a mutant allele of CAK1 in a synthetic
      lethal screen with the Sit4 protein phosphatase. Analysis of several different
      cak1 mutants shows that although the G2 to M transition appears most sensitive to
      loss of Cak1p function, Cak1p is also required for activation of Cdc28p for
      progression from G1 into S phase. Further characterization of these mutants
      suggests that, unlike the CAK identified from higher eukaryotes, Cak1p of budding
      yeast may not play a role in general transcription. Finally, although Cak1
      protein levels and in vitro protein kinase activity do not fluctuate during the
      cell cycle, at least a fraction of Cak1p associates with higher molecular weight
      proteins, which may be important for its in vivo function.

PMID- 9286670
TI  - In vivo analysis of Saccharomyces cerevisiae COX2 mRNA 5'-untranslated leader
      functions in mitochondrial translation initiation and translational activation.
AB  - We have used mutational and revertant analysis to study the elements of the 54
      nucleotide COX2 5'-untranslated leader involved in translation initiation in
      yeast mitochondria and in activation by the COX2 translational activator.
      Pet111p. We generated a collection of mutants with substitutions spanning the
      entire COX2 5'-UTL by in vitro mutagenesis followed by mitochondrial
      transformation and gene replacement. The phenotypes of these mutants delimit a 31
      nucleotide segment, from -16 to -46, that contains several short sequence
      elements necessary for COX2 5'-UTL function in translation. The sequences from 
      16 to -47 were shown to be partially sufficient to promote translation in a
      foreign context. Analysis of revertants of both the series of linker-scanning
      alleles and two short deletion/ insertion alleles has refined the positions of
      several possible functional elements of the COX2 5'-untranslated leader,
      including a putative RNA stem-loop structure that functionally interacts with
      Pet111p and an octanucleotide sequence present in all S. cerevisiae mitochondrial
      mRNA 5'-UTLs that is a potential rRNA binding site.

PMID- 9286671
TI  - The prp1+ gene required for pre-mRNA splicing in Schizosaccharomyces pombe
      encodes a protein that contains TPR motifs and is similar to Prp6p of budding
      yeast.
AB  - The prp (pre-mRNA processing) mutants of the fission yeast Schizosaccharomyces
      pombe have a defect in pre-mRNA splicing and accumulate mRNA precursors at a
      restrictive temperature. One of the prp mutants, prp1-4, also has a defect in
      poly(A)+ RNA transport. The prp1+ gene encodes a protein of 906 amino acid
      residues that contains 19 repeats of 34 amino acids termed tetratrico peptide
      repeat (TPR) motifs, which were proposed to mediate protein-protein interactions.
      The amino acid sequence of Prp1p shares 29.6% identity and 50.6% similarity with
      that of the PRP6 protein of Saccharomyces cerevisiae, which is a component of the
      U4/U6 snRNP required for spliceosome assembly. No functional complementation was
      observed between S. pombe prp1+ and S. cerevisiae PRP6. We examined synthetic
      lethality of prp1-4 with the other known prp mutations in S. pombe. The results
      suggest that Prp1p interacts either physically or functionally with Prp4p, Prp6p
      and Prp13p. Interestingly, the prp1+ gene was found to be identical with the
      zer1+ gene that functions in cell cycle control. These results suggest that
      Prp1p/Zer1p is either directly or indirectly involved in cell cycle progression
      and/or poly(A)+ RNA nuclear export, in addition to pre-mRNA splicing.

PMID- 9286672
TI  - Schizophyllum commune A alpha mating-type proteins, Y and Z, form complexes in
      all combinations in vitro.
AB  - Tha A alpha locus of the basidiomycete fungus, Schizophyllum commune, regulates
      sexual development via proteins Y and Z. Each A alpha mating type encodes unique
      Y and Z isoforms. We used two isoforms of Y (Y4 and Y5) and two isoforms of Z (Z4
      and Z5) in affinity assays of protein binding. These assays identified two types
      of protein interactions. Each full-length Y or Z protein binds to itself and
      other Y or Z proteins regardless of the A alpha mating type from which they are
      encoded (i.e., mating-type independent binding). A second type of binding,
      detected with partial-length polypeptides, occurs only between N-terminal regions
      of Y and Z proteins encoded from different A alpha mating types (e.g., Y4Z5 or
      Y5Z4); we refer to this binding as mating-type dependent binding. Deletion
      analysis shows that the Y4 specificity domain (an N-terminal region conferring
      recognition uniqueness to the Y4 isoform) is essential for mating-type dependent
      binding. Other regions of Y and Z are involved in mating-type independent
      binding. These results, obtained in vitro, raise the possibility that either of
      several protein complexes composed of Y and/or Z proteins may occur in vivo.

PMID- 9286673
TI  - Occurrence of repeat induced point mutation in long segmental duplications of
      Neurospora.
AB  - Previous studies of repeat induced point mutation (RIP) have typically involved
      gene-size duplications resulting from insertion of transforming DNA at ectopic
      chromosomal positions. To ascertain whether genes in larger duplications are
      subject to RIP, progeny were examined from crosses heterozygous for long
      segmental duplications obtained using insertional or quasiterminal
      translocations. Of 17 distinct mutations from crossing 11 different duplications,
      13 mapped within the segment that was duplicated in the parent, one was closely
      linked, and three were unlinked. Half of the mutations in duplicated segments
      were at previously unknown loci. The mutations were recessive and were expressed
      both in haploid and in duplication progeny from Duplication x Normal, suggesting
      that both copies of the wild-type gene had undergone RIP. Seven transition
      mutations characteristic of RIP were found in 395 base pairs (bp) examined in one
      ro-11 allele from these crosses and three were found in approximately 750 bp of
      another. A single chain-terminating C to T mutation was found in 800 bp of arg-6.
      RIP is thus responsible. These results are consistent with the idea that the
      impaired fertility that is characteristic of segmental duplications is due to
      inactivation by RIP of genes needed for progression through the sexual cycle.

PMID- 9286675
TI  - Inbreeding depression and inferred deleterious-mutation parameters in Daphnia.
AB  - DENG and LYNCH recently proposed a method for estimating deleterious genomic
      mutation parameters from changes in the mean and genetic variance of fitness
      traits upon inbreeding in outcrossing populations. Such observations are readily
      acquired in cyclical parthenogens. Selfing and life-table experiments were
      performed for two such Daphnia populations. We observed a significant inbreeding
      depression and an increase of genetic variance for all traits analyzed. DENG and
      LYNCH's original procedures were extended to estimate genomic mutation rate (U),
      mean dominance coefficient (h), mean selection coefficient (s), and scaled
      genomic mutational variance (Vm/Ve). On average, U, h, s and Vm/Ve (indicates an
      estimate) are 0.84 [corrected], 0.30, 0.14 and 4.6E-4, respectively. For the true
      values, the U and h are lower bounds, and s and Vm/Ve upper bounds. The present
      U, h and Vm/Ve are in general concordance with earlier results. The discrepancy
      between the present s and that from mutation-accumulation experiments in
      Drosophila (approximately 0.04) is discussed. It is shown that different
      reproductive modes do not affect gene frequency at mutation-selection equilibrium
      if mutational effects on fitness are multiplicative and not completely recessive.

PMID- 9286674
TI  - Overlapping functions for two G protein alpha subunits in Neurospora crassa.
AB  - Heterotrimeric G proteins, consisting of alpha, beta and gamma subunits, mediate
      a variety of signaling pathways in eukaryotes. We have previously identified two
      genes, gna-1 and gna-2, that encode G protein alpha subunits in the filamentous
      fungus Neurospora crassa. Mutation of gna-1 results in female infertility and
      sensitivity to hyperosmotic media. In this study, we investigate the expression
      and functions of gna-2. Results from Western analysis and measurements of gna-2
      promoter-lacZ fusion activity indicate that gna-2 is expressed during the
      vegetative and sexual cycle of N. crassa in both A and a mating types. Activating
      mutations predicted to abolish the GTPase activity of GNA-2 cause subtle defects
      in aerial hyphae formation and conidial germination. Extensive phenotypic
      analysis of delta gna-2 strains did not reveal abnormalities during vegetative or
      sexual development. In contrast, deletion of gna-2 in a delta gna-1 strain
      accentuates the delta gna-1 phenotypes. delta gna-1 delta gna-2 strains have a
      slower rate of hyphal apical extension than delta gna-1 strains on hyperosmotic
      media. Moreover, delta gna-1 delta gna-2 mutants have more pronounced defects in
      female fertility than delta gna-1 strains. We propose that gna-1 and gna-2 have
      overlapping functions and may constitute a gene family. This is the first report
      of G protein alpha subunits with overlapping functions in eukaryotic microbes.

PMID- 9286676
TI  - Epistasis in measured genotypes: Drosophila P-element insertions.
AB  - Transposon tagging provides an opportunity to construct large numbers of strains
      of organisms that differ by single insertional mutations. By scoring the
      phenotypes of these "measured genotypes," powerful tests of effects of mutations
      on phenotypic expression have been performed. Here we extend this approach by
      constructing with simple crosses all possible two-locus genotypes for each of
      eight pairs of P-element insertions. Analysis of metabolic phenotypes (fat and
      glycogen contents, enzyme activities, total protein, and body weight) of the
      resulting nine genotypes provides direct estimates of additive, dominance, and
      epistatic effects of the mutations. Nested two-way analysis of variance
      identified significant epistatic effects in 27% of the tests (35/128 of the trait
      x P-element combinations). Posterior contrasts were performed to partition the
      epistatic variance into the four orthogonal components of COCKERHAM, and the data
      exhibit a tendency toward additive x dominance and dominance x dominance
      epistasis. Mutations in this study have epistatic effects on metabolic traits
      that are on the same order of magnitude as main (additive and dominance) effects.
      Measured genotypes have been used in other contexts to quantify epistatic effects
      on phenotypic expression, and these results are also briefly reviewed.

PMID- 9286677
TI  - Divergence of the yellow gene between Drosophila melanogaster and D. subobscura:
      recombination rate, codon bias and synonymous substitutions.
AB  - The yellow (y) gene maps near the telomere of the X chromosome in Drosophila
      melanogaster but not in D. subobscura. Thus the strong reduction in the
      recombination rate associated with telomeric regions is not expected in D.
      subobscura. To study the divergence of a gene whose recombination rate differs
      between two species, the y gene of D. subobscura was sequenced. Sequence
      comparison between D. melanogaster and D. subobscura revealed several elements
      conserved in noncoding regions that may correspond to putative cis-acting
      regulatory sequences. Divergence in the y gene coding region between D.
      subobscura and D. melanogaster was compared with that found in other genes
      sequenced in both species. Both, yellow and scute exhibit an unusually high
      number of synonymous substitutions per site (ps). Also for these genes, the
      extent of codon bias differs between both species, being much higher in D.
      subobscura than in D. melanogaster. This pattern of divergence is consistent with
      the hitchhiking and background selection models that predict an increase in the
      fixation rate of slightly deleterious mutations and a decrease in the rate of
      fixation of slightly advantageous mutations in regions with low recombination
      rates such as in the y-sc gene region of D. melanogaster.

PMID- 9286678
TI  - A functional analysis of Notch mutations in Drosophila.
AB  - The Notch gene encodes a receptor protein that is involved in many processes
      during development. Its best understood role is during neurogenesis in a process
      called "lateral inhibition." However, it has been proposed that Notch also has a
      role in defining the proneural clusters in the first place. This raises the
      possibility that the Notch protein is acting as a multifunctional receptor. To
      test this hypothesis, we have carried out a genetic analysis of molecularly
      characterized Notch alleles to identify alleles that affect only one of the two
      proposed functions. Here we present evidence that Notch alleles can be identified
      that appear to affect the function of Notch during either lateral inhibition or
      the definition of proneural clusters. In addition our results indicate that there
      may be discrete regions of the Notch protein required for each function.

PMID- 9286679
TI  - Evolutionary history of the sex-peptide (Acp70A) gene region in Drosophila
      melanogaster.
AB  - In Drosophila the products of the seminal fluid stimulate oviposition and
      suppress remating in the female. Of all the accessory gland peptides (Acp's)
      involved in these two responses, the sex-peptide (coded by the Acp70A gene) is
      among the best characterized at the functional level. A 1.2-kb fragment
      encompassing the Acp70A gene of nine lines from a natural population of D.
      melanogaster and one allele of D. sechellia was sequenced to study the forces
      shaping nucleotide variation within and between species. The coding region of D.
      simulans and D. mauritiana was also sequenced. A Ser to Ala replacement
      polymorphism at the last position of the signal peptide was detected in D.
      melanogaster. The Ser and Ala alleles are at intermediate frequencies. The level
      of nucleotide variation is lower for the derived Ala allele, which is compatible
      with a recent origin and an increase in frequency due to positive selection.
      Variation at the 5' flanking region is structured in two major highly
      differentiated haplotypes, whose distribution does not conform to neutral
      expectations. Selective and/or historical factors could contribute to the
      observed overall patterning of nucleotide variation at the Acp70A region.

PMID- 9286680
TI  - Polymorphism and divergence at a Drosophila pseudogene locus.
AB  - The larval cuticle protein (Lcp) cluster in Drosophila melanogaster contains four
      functional genes and a closely related pseudogene. A 630-bp fragment including
      the larval cuticle pseudogene locus (Lcp psi) was nucleotide sequenced in 10
      strains of D. melanogaster and a 458-bp Lcp psi fragment from D. simulans was
      also sequenced. We used these data to test the hypotheses that the rates of
      synonymous and nonsynonymous substitution are equal, that the absolute levels of
      variation are higher than in functional genes, and that intraspecific
      polymorphism is correlated with interspecific divergence. As predicted,
      synonymous and nonsynonymous substitution rates were equivalent, and overall
      nucleotide divergence between D. melanogaster and D. simulans (Jukes-Cantor
      distance = 0.149 +/- 0.150) was extremely high. However, within-species DNA
      sequence comparisons at Lcp psi revealed lower levels of polymorphism (theta =
      0.001 +/- 0.001) than at many functional loci in D. melanogaster. Using the
      HUDSON, KREITMAN, and AGUADE (HKA) test, we show that the level of polymorphism
      in Lcp psi within D. melanogaster is lower than expected given the amount of
      divergence between D. melanogaster and D. simulans when the pseudogene data are
      compared to the Adh 5' flanking region. Because the Lcp psi lies in a region of
      relatively infrequent recombination, we suggest that the low level of within
      species polymorphism is the result of background selection.

PMID- 9286681
TI  - Chromatin insulator elements block the silencing of a target gene by the
      Drosophila polycomb response element (PRE) but allow trans interactions between
      PREs on different chromosomes.
AB  - Polycomb response elements (PREs) can establish a silenced state that affects the
      expression of genes over considerable distances. We have tested the ability of
      insulator or boundary elements to block the repression of the miniwhite gene by
      the Ubx PRE. The gypsy element and the scs element interposed between PRE and
      miniwhite gene protect it against silencing but the scs' is only weakly
      effective. When the PRE-miniwhite gene construct is insulated from flanking
      chromosomal sequences by gypsy elements at both ends, it can still establish
      efficient silencing in some lines but not others. We show that this can be caused
      by interactions in trans with PREs at other sites. PRE-containing transposons
      inserted at different sites or even on different chromosomes can interact,
      resulting in enhanced silencing. These trans interactions are not blocked by the
      gypsy insulator and reveal the importance of nonhomologous associations between
      different regions of the genome for both silencing and activation of genes. The
      similarity between the behavior of PREs and enhancers suggests a model for their
      long-distance action.

PMID- 9286682
TI  - Discordant rates of chromosome evolution in the Drosophila virilis species group.
AB  - In Drosophila, the availability of polytene chromosome maps and of sets of probes
      covering most regions of the chromosomes allows a direct comparison of the
      organization of the genome in different species. In this work, we report the
      localization, in Drosophila virilis, D. montana, and D. novamexicana, of > 100
      bacteriophage PI clones containing approximately 65 kilobase inserts of genomic
      DNA from D. virilis. Each clone hybridizes with a single euchromatic site in
      either chromosome 1 or chromosome 3 in D. virilis. From these data, it is
      possible to estimate the minimum number of inversions required to transform the
      map positions of the probes in one species into the map positions of the same
      probes in a related species. The data indicate that, in the D. virilis species
      group, the X chromosome has up to four times the number of inversions as are
      observed in chromosome 3. The first photographic polytene chromosome maps for D.
      montana and D. novamexicana are also presented.

PMID- 9286683
TI  - Reproductive isolation and morphogenetic evolution in Drosophila analyzed by
      breakage of ethological barriers.
AB  - This article reports the breaking of ethological barriers through the
      constitution of soma-germ line chimeras between species of the melanogaster
      subgroup of Drosophila, which are ethologically isolated. Female Drosophila
      yakuba and D. teissieri germ cells in a D. melanogaster ovary produced functional
      oocytes that, when fertilized by D. melanogaster sperm, gave rise to sterile
      yakuba-melanogaster and teissieri-melanogaster male and female hybrids. However,
      the erecta-melanogaster and orena-melanogaster hybrids were lethal, since female
      D. erecta and D. orena germ cells in a D. melanogaster ovary failed to form
      oocytes with the capacity to develop normally. This failure appears to be caused
      by an altered interaction between the melanogaster soma and the erecta and orena
      germ lines. Germ cells of D. teissieri and D. orena in a D. melanogaster testis
      produced motile sperm that was not stored in D. melanogaster females. This might
      be due to incompatibility between the teissieri and orena sperm and the
      melanogaster seminal fluid. A morphological analysis of the terminalia of yakuba
      melanogaster and teissieri-melanogaster hybrids was performed. The effect on the
      terminalia of teissieri-melanogaster hybrids of a mutation in doublesex, a
      regulatory gene that controls the development of the terminalia, was also
      investigated.

PMID- 9286684
TI  - The genes raw and ribbon are required for proper shape of tubular epithelial
      tissues in Drosophila.
AB  - The products of two genes, raw and ribbon (rib), are required for the proper
      morphogenesis of a variety of tissues. Malpighian tubules mutant for raw or rib
      are wider and shorter than normal tubules, which are only two cells in
      circumference when they are fully formed. The mutations alter the shape of the
      tubules beginning early in their formation and block cell rearrangement late in
      development, which normally lengthens and narrows the tubes. Mutations of both
      genes affect a number of other tissues as well. Both genes are required for
      dorsal closure and retraction of the CNS during embryonic development. In
      addition, rib mutations block head involution, and broaden and shorten other
      tubular epithelia (salivary glands, tracheae, and hindgut) in much same manner as
      they alter the shape of the Malpighian tubules. In tissues in which the shape of
      cells can be observed readily, rib mutations alter cell shape, which probably
      causes the change in shape of the organs that are affected. In double mutants raw
      enhances the phenotypes of all the tissues that are affected by rib but
      unaffected by raw alone, indicating that raw is also active in these tissues.

PMID- 9286685
TI  - Linkage groups of protein-coding genes in western palearctic water frogs reveal
      extensive evolutionary conservation.
AB  - Among progeny of a hybrid (Rana shqiperica x R. lessonae) x R. lessonae, 14 of 22
      loci form four linkage groups (LGs): (1) mitochondrial aspartate
      aminotransferase, carbonate dehydratase-2, esterase 4, peptidase D; (2)
      mannosephosphate isomerase, lactate dehydrogenase-B, sex, hexokinase-1, peptidase
      B; (3) albumin, fructose-biphosphatase-1, guanine deaminase; (4) mitochondrial
      superoxide dismutase, cytosolic malic enzyme, xanthine oxidase. Fructose
      biphosphate aldolase-2 and cytosolic aspartate aminotransferase possibly form a
      fifth LG. Mitochondrial aconitate hydratase, alpha-glucosidase, glyceraldehyde-3
      phosphate dehydrogenase, phosphogluconate dehydrogenase, and phosphoglucomutase-2
      are unlinked to other loci. All testable linkages (among eight loci of LGs 1, 2,
      3, and 4) are shared with eastern palearctic water frogs. Including published
      data, 44 protein loci can be assigned to 10 of the 13 chromosomes in Holarctic
      Rana. Of testable pairs among 18 protein loci, agreement between Palearctic and
      Nearctic Rana is complete (125 unlinked, 14 linked pairs among 14 loci of five
      syntenies), and Holarctic Rana and Xenopus laevis are highly concordant (125
      shared nonlinkages, 13 shared linkages, three differences). Several Rana
      syntenies occur in mammals and fish. Many syntenies apparently have persisted for
      60-140 x 10(6) years (frogs), some even for 350-400 x 10(6) years (mammals and
      teleosts).

PMID- 9286686
TI  - The Y-chromosomal and autosomal male-determining M factors of Musca domestica are
      equivalent.
AB  - In Musca domestica, male sex is determined by a dominant factor, M, located
      either on the Y, the X or on an autosome. M prevents the activity of the female
      determining gene F. In the absence of M, F becomes active and dictates female
      development. The various M factors may represent translocated copies of an
      ancestral Y-chromosomal M. Double mutants and germ line chimeras show that MY,
      MI, MII, MIII and MV perform equivalent functions. When brought into the female
      germ line, they predetermine male development of the offspring. This maternal
      effect is overruled by the dominant female-determining factor FD. MI and MII are
      weak M factors, as demonstrated by the presence of yolk proteins in MI/+ males
      and by the occurrence of some intersexes among the offspring that developed from
      transplanted MI/+ and MII/+ pole cells. The arrhenogenic mutation Ag has its
      focus in the female germ line and its temperature-sensitive period during
      oogenesis. We propose that MI and Ag represent allelic M factors that are
      affected in their expression. Analysis of mosaic gonads showed that in M.
      domestica the sex of the germ line is determined by inductive signals from the
      surrounding soma. We present a model to account for the observed phenomena.

PMID- 9286687
TI  - Mutation-selection balance under genomic imprinting at an autosomal locus.
AB  - I model the effect of genomic imprinting on the equilibrium allele frequencies at
      an autosomal diallelic locus subject to viability selection and mutation. The
      population size is assumed to be very large; male and female mutation rates may
      be unequal. Different models examine cases of the inactivation of one gene (with
      both complete and partial penetrance) and of differential expression of genes
      according to the parent of origin. In the simplest cases the frequency of the
      deleterious allele is approximately twice that of a dominant nonimprinting
      mutant, but considerably less than that of a recessive nonimprinting mutant.
      Under imprinting, selection and unequal mutation rates interact: other things
      being equal, male-biased mutation leads to lower mutant frequencies under
      maternal imprinting and higher frequencies under paternal imprinting. I also
      model cases where just one allele is imprintable (and the other not). These
      models allow us to predict the frequency of a failure to imprint in a normally
      imprinting system, as well as the frequency of imprinting at a standard
      nonimprinting locus.

PMID- 9286688
TI  - Synteny conservation and chromosome rearrangements during mammalian evolution.
AB  - An important problem in comparative genome analysis has been defining reliable
      measures of synteny conservation. The published analytical measures of synteny
      conservation have limitations. Nonindependence of comparisons, conserved and
      disrupted syntenies that are as yet unidentified, and redundant rearrangements
      lead to systematic errors that tend to overestimate the degree of conservation.
      We recently derived methods to estimate the total number of conserved syntenies
      within the genome, counting both those that have already been described and those
      that remain to be discovered. With this method, we show that approximately 65% of
      the conserved syntenies have already been identified for humans and mice, that
      rates of synteny disruption vary approximately 25-fold among mammalian lineages,
      and that despite strong selection against reciprocal translocations, inter
      chromosome rearrangements occurred approximately fourfold more often than
      inversions and other intra-chromosome rearrangements, at least for lineages
      leading to humans and mice.

PMID- 9286689
TI  - Activation of the lac repressor in the transgenic mouse.
AB  - We have introduced sequences encoding the lac repressor of Escherichia coli into
      the genome of the mouse. One sequence was derived from the bacterial lac operon
      and the other was created by re-encoding the amino acid sequence of lacI with
      mammalian codons. Both versions are driven by an identical promoter fragment
      derived from the human beta-actin locus and were microinjected into genetically
      identical pronuclear stage embryos. All transgenes utilizing the bacterial coding
      sequence were transcriptionally silent in all somatic tissues tested. The
      sequence re-encoded with mammalian codons was transcriptionally active at all
      transgene loci and expressed ubiquitously. Using methylation-sensitive enzymes,
      we have determined the methylation status of lac repressor transgenes encoded by
      either the bacterial or mammalian sequence. The highly divergent bacterial
      sequence was hypermethylated at all transgene loci, while the mammalian sequence
      was only hypermethylated at a high copy number locus. This may reflect a normal
      process that protects the genome from acquiring new material that has an
      abnormally divergent sequence or structure.

PMID- 9286690
TI  - Mu element-generated gene conversions in maize attenuate the dominant knotted
      phenotype.
AB  - The knotted1 gene was first defined by dominant mutations that affect leaf
      morphology. The original allele, Kn1-O, results from a 17-kb tandem duplication.
      Mutator (Mu) insertions near the junction of the two repeats suppress the leaf
      phenotype to different degrees depending on the position of the insertion. The Mu
      insertions also increase the frequency of recombination at Kn1-O to create
      derivative alleles in which the Mu element and one copy of the repeat are lost.
      These derivatives are normal in appearance. Here we describe two derivatives that
      retained the tandem duplication but gained insertions of 1.7 and 3 kb in length
      in place of the Mu element. In each case, the inserted DNA is a sequence that
      normally flanks the distal repeat unit. Thus, each derivative consists of a
      tandem duplication in which the repeat unit has been extended at its distal end
      by the length of the new insertion. The 1.7-kb insertion dampens the phenotype,
      as did the original Mu insertion, whereas the 3-kb insertion completely
      suppresses the knotted phenotype. We propose that gene conversion, stimulated by
      the double-strand break of the Mu excision, gave rise to these derivatives.

PMID- 9286691
TI  - Dissection of a synthesized quantitative trait to characterize transgene
      interactions.
AB  - Six transgenic tobacco lines, each homozygous for the beta-glucuronidase (GUS)
      gene at a different locus, and wild type were selfed and intercrossed to evaluate
      GUS activity in all possible hemizygous, homozygous and dihybrid combinations of
      GUS alleles. The transgenic lines are characterized by their GUS activity (two
      low, three intermediate, one high), T-DNA complexity (four single-copy, two more
      complex single-locus) and the presence of the chicken lysozyme matrix-associated
      region (MAR) around the full T-DNA (two lines). Gene action and interaction was
      analyzed by weighted linear regression with parameters for additivity, dominance
      and epistasis. The analysis showed that each of the four single-copy lines acted
      fully additively. In contrast, the two complex single-locus lines showed
      classical single-locus overdominance and were epistatic dominant over all other
      GUS alleles. The latter is manifested in severe suppression of GUS activity in
      dihybrid lines, irrespective of the presence of MAR elements around the GUS gene.
      Such elements apparently do not protect against epistatic dominance. The
      quantitative data suggested that the epistatic dominance and overdominance are
      based on the same molecular mechanism. Our approach of a genetic analysis of
      quantitative variation in well-characterized transgenic lines provides a powerful
      tool to gain insight into complex plant traits.

PMID- 9286692
TI  - Cytonuclear theory for haplodiploid species and X-linked genes. I. Hardy-Weinberg
      dynamics and continent-island, hybrid zone models.
AB  - We develop models that describe the cytonuclear structure for either a
      cytoplasmic and nuclear marker in a haplodiploid species or a cytoplasmic and X
      linked marker in a diploid species. Sex-specific disequilibrium statistics that
      summarize nonrandom cytonuclear associations in such systems are defined, and
      their basic Hardy-Weinberg dynamics and admixture formulae are delimited. We
      focus on the context of hybrid zones and develop continent-island models whereby
      individuals from two genetically differentiated source populations migrate into
      and mate within a single zone of admixture. We examine the effects of
      differential migration of the sexes, assortative mating by pure type females, and
      census time (relative to mating and migration), as well as special cases of
      random mating and migration subsumed under the general models. We show that pure
      type individuals and nonzero cytonuclear disequilibria can be maintained within a
      hybrid zone if there is continued migration from both source populations, and
      that females generally have a greater influence over these cytonuclear variables
      than males. The resulting theoretical framework can be used to estimate the rates
      of assortative mating and sex-specific gene flow in hybrid zones and other zones
      of admixture involving haplodiploid or sex-linked cytonuclear data.

PMID- 9286693
TI  - Clusters of identical new mutations can account for the "overdispersed" molecular
      clock.
AB  - Germ-cell mutations may occur during meiosis, giving rise to independent mutant
      gametes in a Poisson process, or before meiosis, giving rise to multiple copies
      of identical mutant gametes at a much higher probability than the Poisson
      expectation. We report that the occurrence of these early premeiotic clusters of
      new identical mutant alleles increases the variance-to-mean ratio of mutation
      rate (R(u) > 1). This leads to an expected variance-to-mean ratio (R(t)) of the
      molecular clock that is always greater than one and may cover the observed range
      of R(t) values. Hence, the molecular clock may not be over-dispersed based on
      this new mutational model that includes clusters. To get a better estimation of
      R(u) and R(t), one needs measurements of the intrageneration variation of
      reproductive success (Nt/Ne(i)), population dynamics (ki), and the proportion of
      new mutations that occur in clusters (rc), especially those formed before germ
      cell differentiation.

PMID- 9286694
TI  - Linkage of TATA-binding protein and proteasome subunit C5 genes in mice and
      humans reveals synteny conserved between mammals and invertebrates.
AB  - The TATA-binding protein (TBP) is a factor required for the transcription of all
      classes of eukaryotic genes. Here, we demonstrate that in the mouse the TBP
      encoding gene (Tbp) resides next to the proteasomal subunit C5-encoding gene
      (Psmb1). The genes are located on mouse chromosome 17 in the t complex within the
      Hybrid sterility 1 (Hst1) region. We demonstrate that the homologous human genes
      (TBP AND PSMB1) are tightly linked on the long arm of chromosome 6, in a region
      syntenic with the proximal part of mouse chromosome 17. The mouse Tbp and Psmb1
      and the human TBP and PSMB1 genes are transcribed in the opposite orientation.
      The TATA-binding protein and proteasomal subunit C5 genes are also linked on
      chromosome III of Caenorhabditis elegans, and together they are linked to other
      genes whose homologs map to human chromosome 6 and mouse chromosome 17. In the
      Drosophila genome, the housekeeping TATA-binding protein gene maps close to two
      other genes with homologs in the mammalian major histocompatibility complex.
      There thus exists conserved synteny of unrelated genes between mammals and
      invertebrates.

PMID- 9286695
TI  - Genomic organization of two novel genes on human Xq28: compact head to head
      arrangement of IDH gamma and TRAP delta is conserved in rat and mouse.
AB  - In this paper we present the entire genomic sequence as well as the cDNA sequence
      of two new human genes encoding the gamma subunit of the NAD(+)-dependent
      isocitrate dehydrogenase (H-IDH gamma) and the translocon-associated protein
      delta subunit (TRAP delta). These genes are located on region q28 of the human X
      chromosome, approximately 70 kb telomeric to the adrenoleukodystrophy locus
      (ALD). The sequences of the transcripts of both genes were obtained by searching
      the EST database with genomic data. Identified ESTs were completely sequenced and
      assembled to cDNAs comprising the entire coding region. For IDH gamma, several
      EST clones indicate differential splicing. IDH gamma and TRAP delta are arranged
      in a compact head to head manner. The nontranscribed intergenic region represents
      only 133 bp and is embedded in a CpG island. The CpG island obviously functions
      as a bidirectional promoter to initiate the transcription of both functionally
      unrelated genes with quite distinct expression patterns. This exceptional gene
      arrangement prompted us to clone and sequence genomic DNA fragments containing
      the homologous intergenic regions of rat and mouse. We show that in both species
      this area is similarly compact and represents less than 249 bp in rat and not
      more than 164 bp in mouse. In both cases this intergenic region is embedded in a
      CpG island and is highly conserved with nucleotide identity values ranging from
      70.1% between human and rat to 92.6% between mouse and rat.

PMID- 9286696
TI  - Sequence and chromosomal localization of the mouse brevican gene.
AB  - Brevican is a brain-specific proteoglycan belonging to the aggrecan family. Phage
      clones containing the complete mouse brevican open reading frame of 2649 bp and
      the complete 3'-untranslated region of 341 bp were isolated from a mouse brain
      cDNA library, and cosmid clones containing the mouse brevican gene were isolated
      from a genomic library using a PCR-generated DNA fragment as probe. The obtained
      genomic sequence of 13,700 nucleotides revealed that the murine gene has a size
      of approximately 13 kb and contains the sequence of the mRNA for the secreted
      brevican isoform on 14 exons. The exon-intron structure reflected the structural
      organization of the multidomain protein brevican. No consensus TATA sequence was
      found upstream of the first exon, and RNase protection experiments revealed
      multiple transcriptional start sites for the brevican gene. The first part of the
      sequence of intron 8 corresponded to an alternative brevican cDNA, coding for a
      GPI-linked isoform. Single strand conformation polymorphism analysis mapped the
      brevican gene (Bcan) to chromosome 3 between the microsatellite markers D3Mit22
      and D3Mit11.

PMID- 9286697
TI  - NVL: a new member of the AAA family of ATPases localized to the nucleus.
AB  - We report the cloning of NVL, a newly recognized human gene that encodes an
      approximately 110-kDa nuclear protein designated NVLp (nuclear VCP-like protein),
      which is a member of a rapidly growing family of ATP-binding proteins recently
      denoted the AAA family (ATPases associated with diverse cellular activities) (W.
      H. Kunau et al., 1993, Biochimie 75:209-224). NVL was isolated by degenerate PCR
      using oligonucleotides corresponding to the yeast PEX1 gene, which is necessary
      for peroxisomal biogenesis. Two cDNAs, designated NVL.1 and NVL.2, may represent
      alternatively spliced forms of a single gene that maps to chromosome 1q41-q42.2.
      NVL has greatest similarity to the VCP subfamily of AAA proteins, is widely
      expressed, and encodes a nuclear protein with two highly similar ATP-binding
      domains. We speculate that NVLp is involved in an ATP-dependent nuclear process.

PMID- 9286698
TI  - Contiguous arrays of satellites 1, 3, and beta form a 1.5-Mb domain on chromosome
      22p.
AB  - The centromeric heterochromatin of all the human chromosomes is composed of
      megabases of tandemly repeated satellite DNA. Some of these sequences have been
      implicated in centromere formation and/or segregation but the arrangement of most
      of them on a large scale remains largely uncharacterized because of the
      difficulties in analyzing repetitive DNA. The alpha satellite is the best studied
      and is present in large tandem arrays at all centromeres, but satellites 1, 3,
      and beta have also been detected on a number of chromosomes. Here we have used
      FISH to extended DNA fibers to analyze these satellites on the short arm of the
      acrocentric chromosome 22. The satellite sequences were found to form a
      continuous domain spanning about 1.5 Mb and consisting of a major block of
      satellite 1 flanked by two blocks of beta satellite and three blocks of satellite
      3. These six blocks of satellite DNA appear to form contiguous arrays with little
      intervening DNA.

PMID- 9286699
TI  - Cloning, chromosomal localization, and interspecies interaction of mouse DNA
      polymerase delta small subunit (PolD2).
AB  - DNA polymerase delta core is a heterodimeric enzyme with a catalytic subunit of
      125 kDa and a second subunit of 50 kDa with an as yet unknown function. It is an
      essential enzyme for DNA replication and DNA repair. We cloned the full-length
      cDNA encoding the DNA polymerase delta small subunit from mouse cells. The
      sequence of the predicted polypeptide of 51,336 Da is, like the catalytic
      subunit, highly conserved not only among mammals (93% identity and 96%
      similarity), but also between yeast and mammals (34% identity and 57%
      similarity). Fluorescence in situ hybridization experiments indicated that the
      gene for the small DNA polymerase delta of mouse is localized on chromosome 11,
      band A2. By using the yeast two-hybrid system we found that the mouse 125-kDa DNA
      polymerase catalytic subunit is able to interact with the 50-kDa subunit of the
      human enzyme, suggesting an in vivo interspecies interaction between the two
      subunits of DNA polymerase delta.

PMID- 9286700
TI  - Human estrogen receptor-like 1 (ESRL1) gene: genomic organization, chromosomal
      localization, and promoter characterization.
AB  - Estrogen receptor-like 1a (ESRL1a; same as estrogen receptor-related orphan
      receptors, ERR1) belongs to a subfamily of the nuclear receptor superfamily. We
      have previously shown that human ESRL1a modulates estrogen responsiveness of the
      lactoferrin gene promoter in transiently transfected endometrial carcinoma RL95-2
      cells. In this study, we cloned and characterized the human ESRL1 gene. Through
      the fluorescence in situ hybridization method, the ESRL1 gene was localized to
      the centromere region of chromosome 11q12. Partial sequencing, restriction
      mapping, and PCR analysis revealed that the ESRL1 gene consists of seven exons
      and is approximately 20 kb in length. We found that the smallest exon (exon 3)
      contains 117 bp and the largest exon (exon 7) has 1032 bp. The smallest intron
      (intron 5) is only 88 bp long and the largest intron (intron 2) is 8 kb long. All
      introns have the conserved GT and AG dinucleotides present at the donor and
      acceptor sites, respectively. Like the estrogen receptor, the highly conserved
      DNA-binding domain of hESRL1a is encoded by exon 2 and exon 3, and the
      intron/exon junctions (2 and 3) are well conserved between the two genes. Primer
      extension analysis revealed multiple transcription initiation start sites in
      human uterine (HeLa, HEC, and RL95-2) cell lines. However, one major initiation
      start site was found by RNase protection assay. The hESRL1a mRNA is
      differentially expressed in various human tissues. The nucleotide sequence
      adjacent to the transcription start sites of the ESRL1 lacks the typical TATA and
      CAAT boxes but is GC rich and contains 10 consensus Sp1-binding elements and two
      E boxes. The region that contains these transcription factor-binding elements
      showed a high level of promoter activity when transiently transfected into RL95-2
      cells.

PMID- 9286701
TI  - AFLP-based fine mapping of the Mlo gene to a 30-kb DNA segment of the barley
      genome.
AB  - Resistance of barley (Hordeum vulgare) to the powdery mildew fungus Erysiphe
      graminis f.sp. hordei is conferred by several dominant genes, but also by
      recessive alleles of the Mlo locus mapping on the long arm of chromosome 4. In
      addition, this single-factor-mediated resistance is active against all known
      physiological races of the parasite. Thus the mechanism underlying mlo-mediated
      resistance should differ substantially from that mediated by the dominant genes.
      A positional cloning strategy to isolate the Mlo gene from the barley genome, the
      size of which is almost double the size of the human genome, has been designed.
      The AFLP technique was employed to identify markers tightly linked to the Mlo
      locus and to produce a local high-resolution genetic map. The use of this high
      volume marker technology allowed the rapid screening of approximately 250,000
      loci for linkage to Mlo. A large number of Mlo-linked AFLP markers were
      identified, one of which cosegregated with Mlo on the basis of more than 4000
      meiotic events. A four-genome-equivalent barley YAC library (average insert size
      480 kb) was constructed and screened with this cosegregating marker. Four YACs
      containing this marker were isolated and subsequent characterization by AFLP
      based physical mapping allowed the physical delimitation of the Mlo locus to a
      DNA segment of 30 kb.

PMID- 9286702
TI  - Human postsynaptic density-95 (PSD95): location of the gene (DLG4) and possible
      function in nonneural as well as in neural tissues.
AB  - We have determined the cDNA sequence, expression pattern, and chromosomal
      location of the human gene DLG4, encoding the postsynaptic density-95 (PSD95)
      protein. hPSD95 is a 723-amino-acid protein that is 99% identical to its rodent
      counterparts. This is the fourth human protein identified as showing significant
      similarity to the Drosophila tumor suppressor Dlg. These proteins constitute the
      DLG subfamily of the membrane-associated guanylate kinase protein family. The
      expression of DLG4 in neural tissue is consistent with the pattern observed for
      its rat homolog. However, DLG4 is also expressed in a wide range of nonneural
      tissues, suggesting that the protein may have additional roles in humans. Using
      radiation-hybrid mapping panels, we mapped the DLG4 locus to 17p13.1, a region
      associated with several diseases, the phenotypes of which are consistent with
      loss of PSD95 function.

PMID- 9286703
TI  - Cloning, structural analysis, and chromosomal localization of the human CSRP2
      gene encoding the LIM domain protein CRP2.
AB  - The CSRP2 gene encoding the LIM domain protein CRP2 was originally identified in
      quail based on its strong transcriptional suppression in transformed avian
      fibroblasts. Here we have isolated a human CSRP2 cDNA clone encoding a 193-amino
      acid human CRP2 (hCRP2) protein with 96.4% amino acid sequence identity to the
      avian homolog. The CSRP2 cDNA clone was used to isolate CSRP2-related clones from
      gamma EMBL3 and P1 libraries of human genomic DNA. The complete organization of
      the CSRP2 gene was determined by nucleic acid hybridization, transcriptional
      mapping, and nucleotide sequence analysis. The gene spans a total of
      approximately 22 kb and contains six exons. The coding region is confined to
      exons 2-6 and predicts a hCRP2 protein identical in its amino acid sequence to
      the protein deduced from the CSRP2 cDNA clone. By fluorescence in situ
      hybridization using both lambda EMBL3 and P1 library clones as hybridization
      probes and a new method for computerized signal localization, CSRP2 was mapped to
      chromosome subband 12q21.1, a region frequently affected by deletion or breakage
      events in various tumor types. The library screens also led to the isolation of a
      CSRP2-related pseudogene, CSRP2P, which carried several extensive deletions and
      nucleotide substitutions but no intervening sequences in comparison to the CSRP2
      cDNA sequence. By physical linkage and fluorescence in situ hybridization, CSRP2P
      was mapped to chromosome subband 3q21.1.

PMID- 9286705
TI  - Gene structure and chromosome localization of the G gamma c subunit of human cone
      G-protein (GNGT2).
AB  - Phototransduction in the vertebrate rod and cone photoreceptors is regulated by
      structurally homologous and yet distinct groups of signaling proteins. We have
      previously identified in bovine retinas a cone-specific G-protein gamma subunit
      (G gamma c, previously named G gamma b), which may play a key role in coupling
      the cone visual pigment to phosphodiesterase (O. C. Ong et al., 1995, J. Biol.
      Chem. 270:8495-8500). We report here the characterization of human G gamma c and
      its gene structure. Human G gamma c subunit shares a high degree of sequence
      identity with the corresponding bovine G gamma c isoform (85%) and human rod G
      gamma 1 (63%). The protein is specifically localized in cones, as indicated by
      immunohistochemical staining using anti-G gamma c antibodies. Nucleotide sequence
      analysis of the G gamma c gene (GNGT2) reveals a structure consisting of three
      exons and two introns, with the intron splice sites similar to that of the rod G
      gamma 1 gene (GNGT1). By using fluorescence in situ hybridization, we have
      further localized the human GNGT2 gene to chromosome 17q21. The elucidation of
      the G gamma c gene structure would facilitate the identification of genetic
      defects associated with cone degeneration.

PMID- 9286704
TI  - Construction of a 1.2-Mb sequence-ready contig of chromosome 11q13 encompassing
      the multiple endocrine neoplasia type 1 (MEN1) gene. The European Consortium on
      MEN1.
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant familial
      cancer syndrome characterized by parathyroid, pancreatic, and anterior pituitary
      tumors. The MEN1 locus has been previously localized to chromosome 11q13, and a 2
      Mb gene-rich region flanked by D11S1883 and D11S449 has been defined. We have
      pursued studies to facilitate identification of the MEN1 gene by narrowing this
      critical region to a 900-kb interval between the VRF and D11S1783 loci through
      melotic mapping. This was achieved by investigating 17 cosmids for microsatellite
      polymorphisms, which defined two novel polymorphisms at the VRF and A0138 loci,
      and utilizing these to characterize recombinants in MEN1 families. In addition,
      we have established a 1200-kb sequence-ready contig consisting of 26 cosmids,
      eight BACs, and eight PACs that encompass this region. The precise locations for
      19 genes and three ESTs within this contig have been determined, and three gene
      clusters consisting of a centromeric group (VRF, FKBP2, PNG, and PLCB3), a middle
      group (PYGM, ZFM1, SCG1, SCG2 (which proved to be the MEN1 gene), and PPP2R5B),
      and a telomeric group (H4B, ANG3, ANG2, ANG1, FON, FAU, NOF, NON, and D11S2196E)
      were observed. These results represent a valuable transcriptional map of
      chromosome 11q13 that will help in the search for disease genes in this region.

PMID- 9286706
TI  - Physical mapping of potassium channel gene clusters on mouse chromosomes three
      and six.
AB  - Mammalian voltage-gated K channel genes have been divided into four subfamilies
      (Shaker, Shab, Shal, and Shaw) based on their sequence identity and similarity to
      related genes in Drosophila. Genetic mapping of the voltage-gated K channel genes
      has shown that similar multigene clusters exist on mouse Chr 3 and 6 and suggests
      that the clusters may have arisen through chromosomal duplication. In this
      report, YAC-based physical maps of the clustered mouse Shaker-like K channel
      genes have been constructed using restriction endonuclease and yeast chromosome
      fragmentation approaches. These data define the physical spacing as 5'-Kcna3-(60
      kb)-Kcna2-(90 kb)-Kcna8-3' on Chr 3, and as 5'-Kcna6-(80 kb)-Kcna1-(110 kb)-Kcna5
      3' on Chr 6, with all genes oriented in a head-to-tail manner within their
      respective clusters. These detailed physical maps of both K channel gene clusters
      provide additional support for the idea of an ancient genome tetraploidization
      event.

PMID- 9286707
TI  - The Sycp1 loci of the mouse genome: successive retropositions of a meiotic gene
      during the recent evolution of the genus.
AB  - The murine Sycp1 gene is expressed at the early stages of meiosis. We show that
      it is composed of a number of small exons and localized on mouse chromosome 3. In
      the laboratory strains, two retrogenes were also identified. The first one (Sycp1
      ps1), on chromosome 7, has accumulated point mutations and deletions and is not
      transcribed. A second retrogene (Sycp1-ps2), on chromosome 8, is inserted within
      the continuity of a moderately repeated element, in an intron of another gene
      (Cad11). The two retroposition events can be dated to distinct periods in the
      evolution of the Muridae. Sycp1-ps2 has kept features indicative of a relatively
      recent origin, namely a nearly intact coding region, a poly(A) tail, and 14-bp
      terminal repeats. Its recent origin was confirmed by the fact that it is found in
      all the laboratory strains of mice, but neither in a recent isolate from Mus
      musculus domesticus wild stocks nor in the closely related subspecies M. musculus
      musculus, M. m. molossinus, M. m. castaneus, and M. m. bactrianus. Appearance of
      the more ancient Sycp1-ps1 retrogene is concomitant with the radiation of the
      genus. It is present in various Mus species (M. spretus, M. spicilegus, M.
      macedonicus, and M. cookii), but neither in the rat nor in the more closely
      related Pyromis genus. Transposition of retrotranscripts during meiosis and their
      hereditary establishment thus appear to occur relatively frequently. They may,
      therefore, play a significant role in the evolutionary process.

PMID- 9286708
TI  - Chromosomal localization of the human P2y6 purinoceptor gene and phylogenetic
      analysis of the P2y purinoceptor family.
AB  - The G-protein-coupled P2Y purinoceptors mediate a variety of physiological
      effects in response to extracellular nucleotides. With the recent discovery of
      several new members from a variety of species, the P2Y purinoceptor family now
      encompasses types P2Y1 to P2Y6. By fluorescence in situ hybridization and
      utilization of the National Center for Biotechnology Information (NCBI) database,
      the human P2Y6 gene was localized to chromosome 11q13.5, between polymorphic
      markers D11S1314 and D11S916. NCBI database analysis of the remaining human P2Y
      purinoceptor genes revealed that P2Y2 and P2Y6 mapped to within less than 4 cM,
      and thus constitute the first described chromosomal clustering of this gene
      family. Phylogenetic analysis of the P2Y purinoceptor family demonstrated the
      presence of five evolutionary branches and suggests the occurrence of an ancient
      gene duplication event.

PMID- 9286709
TI  - Characterization of the exon structure of the polycystic kidney disease 2 gene
      (PKD2).
AB  - PKD2, the gene defective in the second form of autosomal dominant polycystic
      kidney disease (ADPKD), has been identified by positional cloning and found to
      encode an integral membrane protein with similarity to the gene for the more
      common form of ADPKD and to calcium channels. We have determined the exon-intron
      structure of the PKD2 gene. PKD2 is encoded in at least 15 exons with the
      translation start site in exon 1. All the splice acceptor and donor sites conform
      to the AG/GT rule. We have designed a series of intronic oligonucleotide primers
      for amplifying the entire coding sequence from genomic DNA in segments well
      suited to mutation analysis using conventional screening strategies such as SSCA
      or heteroduplex analysis.

PMID- 9286710
TI  - Neurturin, a novel neurotrophic factor, is localized to mouse chromosome 17 and
      human chromosome 19p13.3.
AB  - Neurturin is a potent neurotrophic factor closely related to glial cell line
      derived neurotrophic factor (GDNF, 40% amino acid sequence identity) and, like
      GDNF, can promote the survival of numerous neuronal populations including
      sympathetic, nodose, and dorsal root ganglion sensory neurons. Both neurturin and
      GDNF signal through the Ret tyrosine kinase and require a
      glycosylphosphatidylinositol-linked coreceptor. Mutations in Ret and GDNF cause
      intestinal aganglionosis and renal dysplasia. Activating Ret mutations also cause
      multiple endocrine neoplasia syndromes (MEN2A and MEN2B). We have isolated mouse
      and human genomic neurturin clones. The sequence for preproneurturin is encoded
      by two exons. Mouse and human clones have common intron/exon boundaries. We have
      used interspecific backcross analysis to localize neurturin to mouse chromosome
      17 near the Vav locus and fluorescence in situ hybridization analysis to localize
      human neurturin to the syntenic region of human chromosome 19p13.3.

PMID- 9286712
TI  - Lhx4, a LIM homeobox gene.
AB  - LIM homeobox genes are well conserved in evolution and play important roles as
      transcriptional regulators of embryonic development. Here we report on the
      structure of LIM domains of the mouse Lhx4 (Gsh4) gene. The cDNA was generated by
      modified reverse transcription-PCR from midgestation embryo templates, using a
      degenerate consensus primer. The deduced amino acid sequence of the first LIM
      domain reveals 77% identity and that of the second domain reveals 86% identity
      with the corresponding sequences of the closely related Lhx3 gene. In addition,
      there is 38-56% similarity to other members of the Lhx gene family. The LIM
      consensus sequence is well conserved in Lhx4.

PMID- 9286711
TI  - Localization of the squalene epoxidase gene (SQLE) to human chromosome region
      8q24.1.
AB  - Squalene epoxidase (EC 1.14.99.7) catalyzes the first oxygenation step in sterol
      biosynthesis and is suggested to be one of the rate-limiting enzymes in this
      pathway. We previously isolated the mammalian squalene epoxidase cDNAs and
      demonstrated the transcriptional regulation of human squalene epoxidase by
      sterols and inhibitors. The present study was undertaken to determine the
      chromosomal mapping of the human squalene epoxidase gene (SQLE). PCR evidence
      localizes human SQLE to chromosome 8 by using the NIGMS (National Institute of
      General Medical Sciences) Human/Rodent Somatic Cell Hybrid Mapping Panel 2 as
      template. To refine the localization of human SQLE further, PCR on the Stanford
      G3 Radiation Hybrid Panel was performed. The result shows that human SQLE is most
      tightly linked to D8S508, which is reported to be located at 8q24.13-qter (lod
      score 7.87). Moreover, fluorescence in situ hybridization also maps human SQLE to
      8q24.1.

PMID- 9286714
TI  - Localization of the gene coding for myosin phosphatase, target subunit 1 (MYPT1)
      to human chromosome 12q15-q21.
AB  - Myosin phosphatase target subunit 1 (MYPT1), which is also called the myosin
      binding subunit of myosin phosphatase, is one of the subunits of myosin
      phosphatase. Myosin phosphatase regulates the interaction of actin and myosin
      downstream of the guanosine triphosphatase Rho, as previously shown (K. Kimura,
      et al., 1996, Science 273:245-248). To understand the role of MYPT1 in the
      regulation of the cytoskeleton in human diseases, we have cloned a 4855-bp cDNA
      for human MYPT1 using the rat MYPT1 cDNA as probe. Sequencing analysis has
      revealed that human MYPT1 contains 1030 amino acid residues with a calculated
      molecular mass of approximately 115 kDa. Fluorescence in situ hybridization
      analysis placed the human MYPT1 gene on chromosome 12q15-q21.2. Radiation hybrid
      mapping has shown that the human MYPT1 gene is located very near the highly
      polymorphic marker CHLC.GATA65A12, which lies between D12S350 and D12S106.

PMID- 9286713
TI  - Molecular characterization and localization of the human MAFG gene.
AB  - The human MAFG gene encodes a basic-leucine zipper (bZIP) protein that belongs to
      a family of transcription factors related to the v-maf oncogene. The ubiquitously
      expressed MAFG protein dimerizes with blood cell-specific bZIP factor p45 NF-E2,
      indicating that it may play a role in regulating hematopoietic gene expression.
      We have characterized the human MAFG gene and shown that it consists of at least
      three exons, which are separated by small introns. The first exon is not
      translated. The genomic structure of the MAFG locus is highly conserved between
      human and chicken. We have mapped the MAFG gene to human chromosome region 17q25
      by fluorescence in situ hybridization. Several putative human disease loci have
      been mapped to this telomeric portion of chromosome 17.

PMID- 9286717
TI  - Lumbar epidural analgesia for labor and vaginal delivery.
AB  - Lumbar epidural analgesia has become the preferred method of pain relief for
      labor and delivery. Proper administration of epidural analgesia offers many
      advantages for both mother and fetus. With the availability of various local
      anesthetics, opioids, and infusion techniques, the analgesia can be tailored to
      the specific needs of the mother, fetus, and labor. Its effect on the progress of
      labor remains a controversial topic subject to ongoing investigation.

PMID- 9286715
TI  - Localization of the mouse gene (Bc1) encoding neural BC1 RNA near the fibroblast
      growth factor 3 locus (Fgf3) on distal chromosome 7.

PMID- 9286718
TI  - Effect of magnesium sulfate treatment on neonatal bone abnormalities.
AB  - OBJECTIVE: It has been reported that neonatal bone abnormalities occur as a
      result of long-term intravenous magnesium administration (MgSO4) to pregnant
      women. The purpose of this retrospective study was to evaluate the frequency of
      such abnormalities and the clinical background of both mothers and neonates.
      PATIENTS AND METHODS: We reviewed maternal (114 cases) and neonatal (139 cases)
      charts from all pregnant women who received intravenous MgSO4 administration for
      preterm labor and preeclampsia between June 1, 1992, and May 31, 1994. All chest
      X-ray films were obtained within 48 h after birth and reviewed by a doctor who
      was unaware of the clinical data. Radiolucent transverse metaphyseal bands of the
      proximal humerus were considered as abnormal. The subjects were divided into
      affected (group 1 and 1a) and unaffected (group 2 and 2a) groups. Neonates born
      to pregnant women given no MgSO4 at the same period, were considered as control.
      RESULTS: The total number of bone abnormalities in the offspring of mothers
      receiving MgSO4 amounted to 13 (11.4%). Group 1 consisted of 13 cases and group 2
      of 101 cases. In the control group bone abnormalities were not observed (p <
      0.05). Significant differences were found between groups 1 and 2 in the
      gestational ages at the start of MgSO4 administration and at delivery, and in the
      total duration of administration and doses of MgSO4. Also, cases of multiple
      pregnancy and pregnancy complicated with impaired glucose tolerance were more
      prevalent in group 1. According to the results obtained from 139 neonates, cases
      showing low Apgar and high magnesium score and those receiving respiratory
      support were more noticeable in group 1a (15 cases). CONCLUSIONS: The gestational
      ages and the total doses of MgSO4 in pregnant women were the main factors related
      to the onset of neonatal bone abnormalities, but other factors also have a
      possible bearing on the condition. In addition, the cases with onset of bone
      abnormality seemed to be associated with symptoms attributable to hypermagnesemia
      of neonates.

PMID- 9286719
TI  - Placental glucose transporters in fetal intrauterine growth retardation and
      macrosomia.
AB  - To investigate the role of placental glucose delivery in fetal growth, two
      glucose transporters (Glut3 and Glut4) were determined from term placentae. This
      was accomplished by immunoblotting from crude placental membrane samples from
      cases of fetal intrauterine growth retardation (IUGR, n = 6), macrosomia (n = 6),
      maternal diabetes mellitus (n = 4) and normal term (n = 8). Glut3 and Glut4 were
      detected in only very low numbers in all patient groups and there were no changes
      in their placental density, which suggests that the expression of these
      transporters is not involved in disorders of fetal growth. However, birth weight
      corresponded to placental weight, indicating that the total amount of Glut3 and
      Glut4 is reduced in IUGR and increased in macrosomia.

PMID- 9286720
TI  - Differences in mRNA expression of endothelin-1, c-fos and c-jun in placentas from
      normal pregnancies and pregnancies complicated with preeclampsia and/or
      intrauterine growth retardation.
AB  - A defect in placental function has been suggested to be associated both with
      preeclampsia (PE), with or without concomitant intrauterine growth retardation
      (IUGR), and with IUGR as a single entity. Our aim was to compare the mRNA
      expression of the growth-related protooncogenes c-fos and c-jun and the
      vasoconstrictor and growth factor endothelin-1 (ET-1) in placentas from normal
      pregnancies with those of PE and IUGR. The mRNA expression of c-jun was
      significantly higher in all groups of complicated pregnancies while ET-1 and c
      fos mRNA expression was significantly higher only in the group with IUGR. These
      results support the concept that an aberrant placental mRNA expression of the ET
      1, c-fos and c-jun genes is part of an altered pattern of gene expression in
      pathological pregnancies.

PMID- 9286721
TI  - Elevation of the serum uric acid level preceding the clinical manifestation of
      preeclampsia in twin pregnancies.
AB  - To assess changes in the serum uric acid level in the third trimester of twin
      pregnancies, a total of 152 consecutive women with twin pregnancies were
      examined. Serum uric acid levels were analyzed in the women at varying
      gestational weeks in the presence or absence of preeclampsia. A receiver
      operating characteristic curve was used to determine the optimal cutoff value of
      serum uric acid between 30 and 31 weeks of gestation predicting subsequent
      development of preeclampsia. Forty-four women (29%) developed preeclampsia
      (preeclampsia group) at 33.2 +/- 1.9 weeks (mean +/- SD) and gave birth at 35.4
      +/- 1.5 weeks of gestation. The remaining 108 women (71%) gave birth at 35.6 +/-
      1.7 weeks of gestation (control group without preeclampsia). Serum uric acid
      levels rose gradually with advancing gestation in both groups. In the
      preeclampsia group, they were already increased at 30-31 weeks of gestation and
      corresponded to those seen in the control group at 37 weeks. The cutoff value at
      30-31 weeks was 5.5 mg/dl, with a sensitivity of 73% and a specificity of 74%.
      These results suggest that an elevation in serum urate preceded the onset of
      preeclampsia. Determination of the serum level of uric acid between 30 and 31
      weeks of gestation was useful for detecting a higher risk of late-onset
      preeclampsia in twin pregnancies.

PMID- 9286722
TI  - Parathyroid-hormone-related protein in human milk and its relation to milk
      calcium.
AB  - Parathyroid-hormone-related protein (PTHrP) is found in high concentrations in
      human milk. One of the possible physiological roles of PTHrP may be the
      regulation of calcium transport through the mammary gland. The relationship
      between milk PTHrP and Ca concentrations was evaluated in lactating women in the
      present study. Milk PTHrP has been quantified by immunoradiometric assay (IRMA)
      and radioimmunoassay (RIA). The IRMA detects PTHrP 1-72, and the RIA
      carboxyterminal region of PTHrP (C-PTHrP). Milk PTHrP 1-72 and C-PTHrP
      concentrations did not significantly change by breast-feeding. Milk PTHrP 1-72
      changed significantly by the time of day, in contrast to C-PTHrP. Thus, PTHrP 1
      72 rather than C-PTHrP may reflect an acute change in mammary PTHrP secretion. In
      lactating women in whom milk PTHrP and calcium concentrations were serially
      measured at 5-day intervals up to 26-30 days after delivery, milk PTHrP 1-72
      progressively increased with duration of lactation. In contrast to PTHrP 1-72,
      milk C-PTHrP decreased during this period. And milk PTHrP 1-72 levels inversely
      correlated with C-PTHrP levels. Milk C-PTHrP but not PTHrP 1-72 levels correlated
      significantly with milk Ca concentrations. Although it is not certain whether the
      correlation between milk C-PTHrP and Ca levels is causally related, it may be
      that fragments of PTHrP detected as C-PTHrP are involved in the regulation of Ca
      transport through the mammary gland in women.

PMID- 9286723
TI  - Increased incidence of preeclampsia in pregnancies complicated by fetal
      malformation.
AB  - There seems to be a correlation between preeclampsia and congenital
      abnormalities, but whether it is positive or negative is a matter of controversy.
      Since it has been demonstrated that reduced perfusion of the trophoblast, which
      is an early feature of preeclampsia, can also represent a cause of fetal
      malformation, a positive correlation between the two conditions should be found.
      In the search for such a correlation we retrospectively examined 8,894 cases
      collected until 1994 by the IMER group (Indagine Malformazioni Emilia-Romagna).
      In the presence of malformation a higher incidence of preeclampsia was found
      (4.60 versus 3.47) with an odds ratio of 1.34 (95% CI = 1.08-1.67). Furthermore
      multivariate analysis showed that malformations of the male genital apparatus and
      those named 'multiple congenital abnormalities' can be considered as risk factors
      for preeclampsia. Since it is known that the development of male genitalia occurs
      under the influence of androgens, it can be hypothesized that hypoxia could act
      by favoring low end organ responsiveness. In our opinion the positive correlation
      with fetal malformations should be interpreted as clinical evidence of the early
      onset of the physiopathologic mechanism of preeclampsia.

PMID- 9286725
TI  - Transvaginal interstitial laser treatment of the ovary for the management of
      chronic hyperandrogenic anovulation: first clinical experience.
AB  - The feasibility of ultrasound-guided transvaginal interstitial laser treatment of
      the ovary (TILT) and its efficacy for ovulation induction was investigated in 3
      hormone-therapy-resistant patients with chronic hyperandrogenic anovulation. TILT
      was performed at powers of 1-2 W and exposures of 75-600 s. Clear-cut
      hyperechogenic zones developed during laser irradiation with diameters of up to
      13.7 mm. Spontaneous ovulation and/or hormonal changes after TILT did not occur.
      No adhesion formation was seen during a laparoscopy or laparotomy in 2 patients 6
      months after TILT. In conclusion, TILT of the ovaries was simple to perform but
      so far the clinical results are disappointing. Further studies with a modified
      technique are necessary to further investigate the efficacy of TILT.

PMID- 9286724
TI  - Efficacy of methotrexate and misoprostol for early abortion.
AB  - BACKGROUND: Medical termination of pregnancy (medical abortion) as an alternative
      to surgical abortion has many advantages since it does not require anesthetics
      and there is no risk of cervical laceration or uterine perforation. In the
      present study, we evaluated the efficacy of methotrexate and intravaginally
      administered misoprostol for early abortion. METHODS: The study population
      consisted of 32 women seeking abortion of a normal intrauterine pregnancy of 8
      weeks or less documented by ultrasound. The dose of methotrexate was 50 mg/m2
      intramuscularly and the dose of misoprostol was 800 micrograms intravaginally.
      The final outcome of treatment was evaluated on day 14 or 16, and an abortion was
      considered successful if pregnancy was terminated without a surgical procedure.
      RESULTS: Abortion occurred in only 23 (71.8%) of 32 women. There were 9 failures
      (28.1%); 3 were ongoing pregnancies (9.3%) and 6 were incomplete abortions
      (18.7%) requiring suction curettage. After the exclusion of treatment failures,
      the mean duration of vaginal bleeding was 16.3 +/- 2 days. No serious side
      effects occurred as a result of methotrexate and misoprostol treatment.
      CONCLUSION: The use of methotrexate and intravaginal misoprostol for the
      termination of pregnancy requires larger studies to determine the safety and
      efficacy of this medical abortion, a comparison with RU 486 in prospective
      controlled randomized trials is necessary.

PMID- 9286726
TI  - Suppression of serum prolactin levels after an oral glucose tolerance test in
      patients with polycystic ovarian syndrome.
AB  - In order to assess if an oral glucose load has any effect on serum prolactin
      levels in patients with polycystic ovary syndrome (PCOS), an oral glucose
      tolerance test (OGTT) was performed in 30 patients with PCOS and 20 controls,
      with normal or abnormal body mass index (BMI). OGTT resulted in decreased
      prolactin levels, being significant only in patients with PCOS and in controls
      with normal BMI. Our results show that obesity is an important inhibiting factor
      of serum prolactin level suppression which occurs with a mild suppressive test,
      as the OGTT; however, hyperandrogenemia may also play an inhibiting role in serum
      prolactin level suppression.

PMID- 9286727
TI  - Prolactin serum levels in postmenopausal women receiving long-term hormone
      replacement therapy.
AB  - In the literature there are different opinions about serum prolactin levels after
      the menopause and in women using hormone replacement therapy. We report serum
      prolactin levels of 165 women after surgical or natural menopause who received
      different kinds of hormone replacement therapies over 2 years and 6 months.
      Surgically or naturally menopausal women showed no significant differences in
      serum prolactin levels. After starting hormone replacement therapy, the serum
      prolactin levels decreased. During subsequent treatment cycles, serum prolactin
      showed varying levels within the reference limits. Women using hormone
      replacement therapy developed no new manifestation of hyperprolactinemia.

PMID- 9286728
TI  - Androgen serum levels in women with premature ovarian failure compared to fertile
      and menopausal controls.
AB  - OBJECTIVE: The purpose of our study was to examine androgen serum levels and bone
      density in women with premature ovarian failure (POF) compared to healthy normal
      controls. STUDY DESIGN: Thirty-three women 19-35 years of age with idiopathic POF
      were compared to 33 well-matched women with normal ovarian function and 32
      healthy postmenopausal (PMP) women concerning 17-hydroxyprogesterone (17-OHP),
      androstendione (A), testosterone (T), dehydroepiandrosterone-sulfate (DHEAS),
      insulin-like growth factor 1 (IGF-1), as well as bone density (BD). RESULTS:
      Women with POF showed statistically significantly lower concentrations of 17-OHP,
      A, T (p < 0.001) and a reduced bone density (p < 0.001) compared to fertile
      controls. No differences were found between POF and PMP women concerning
      estradiol (E2), T, A and 17-OHP. Regarding DHEAS, no statistically significant
      differences were found between women with POF and fertile controls whereas PMP
      women proved to have significantly lower DHEAS concentrations than fertile
      controls. Women with POF had the highest IGF-1 serum concentrations and PMP women
      the lowest. CONCLUSION: An important decrement of ovarian steroids and bone
      density was noticed in women with POF, while the time since menopause had no
      influence on androgen concentrations. The hormone concentrations in women with
      POF are similar to those observed in normal PMP women with the exception of DHEAS
      and IGF-1 levels.

PMID- 9286729
TI  - ras p21 immunohistochemical detection in human endometrial carcinomas.
AB  - Tissue samples of 40 patients with histologically confirmed endometrial cancer
      were analyzed immunohistochemically on paraffin-embedded specimens to detect ras
      p21 protein expression. The relationship between p21 protein expression and
      clinicopathological findings was also analyzed. The intensity and distribution of
      specific cytoplasmatic staining were evaluated semiquantitatively by counting the
      immunohistochemical H-score. ras p21 expression was found in 30 (75%) of 40 human
      endometrial carcinomas, regardless of the clinical stage of the disease. Positive
      immunostaining for p21 was noted in 68% of stage I-II and in all 8 of the
      advanced stages (III-IV according to FIGO) of endometrial carcinomas. Myometrial
      invasion was related to ras p21 immunostaining (p = 0.009), however, no
      correlation between histological findings and ras p21 expression was observed.

PMID- 9286730
TI  - C-myc mutation detected by polymerase chain reaction--heteroduplex in cervical
      cancer.
AB  - To evaluate both the incidence of c-myc gene mutation and the relationship of
      this finding to the clinico-pathologic characteristics of patients with cervical
      cancer, a polymerase chain reaction (PCR)-based heteroduplex gel electrophoresis
      method was used to screen DNA extracted from 102 cervical invasive carcinomas
      referred to the Department of Obstetrics and Gynaecology, The Chinese University
      of Hong Kong. C-myc mutation was detected and then characterised by sequencing of
      PCR products in 4 cases (4%). The incidence of c-myc mutation in patients with
      advanced stage tumours (stage III-IV, 11% was statistically higher than in those
      with early stages (stage I-II, 1%, p = 0.05). There was also a significant
      difference in the incidence of c-myc mutation among the patients who had died of
      their disease (10%), were alive with evidence of disease (25%), and those without
      evidence of disease (0%, p = 0.0003). These findings indicate that the c-myc
      mutation is not common in cervical cancer, but where it exists, it may be
      associated with cancer progression and poorer outcome. Whether the c-myc mutation
      is an adjunct prognostic indicator in cervical cancer remains to be established
      in a larger study.

PMID- 9286732
TI  - Oestrogens and follicular and oocyte development.

PMID- 9286731
TI  - Pure Leydig cell tumour (hilus cell) of the ovary: a rare cause of virilization
      after menopause.
AB  - A 58-year-old postmenopausal woman with high plasma testosterone levels and
      virilization, as demonstrated by hirsutism and alopecia, is presented. Urinary 17
      ketosteroids and 17-hydroxycorticosteroids as well as the computed axial
      tomography scan of the adrenal glands were normal. Although no pelvic mass was
      detected by sonography or pelvic examination, the patient was found to have small
      pure Leydig cell tumour of the left ovary. Following total abdominal hysterectomy
      and bilateral salpingo-oophorectomy, the patient had regression of the hirsutism,
      and the plasma testosterone dropped to normal level.

PMID- 9286734
TI  - Follicular development and oocyte maturation in hypogonadotrophic women employing
      recombinant follicle-stimulating hormone: the role of oestradiol.
AB  - Both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are required
      for follicle development and oestrogen production. Moreover, under normal
      conditions a close association between dominant follicle size and serum and
      intrafollicular oestradiol levels is observed. With the recent availability of
      human recombinant FSH (recFSH), it was possible for the first time to study
      effects of FSH alone, in the complete absence of endogenous or exogenous LH, on
      ovarian function. Recent studies applying recFSH in hypogonadotrophic women have
      shown convincingly that normal growth of follicles up to the preovulatory stage
      occurs despite extremely low oestradiol levels, in keeping with previous
      observations using exogenous gonadotrophins in women incapable of synthesizing
      oestradiol due to steroid enzyme abnormalities. Insufficient data are presently
      available in humans to conclude whether or not oocyte quality is compromised
      under these circumstances. It should, however, be realized that sufficient
      oestradiol levels are required for fertilization in vivo. Therefore LH, or human
      chorionic gonadotrophin (HCG), should be added to stimulation protocols in
      hypogonadotrophic individuals. These observations may also be relevant for
      monitoring of ovarian response during recFSH therapy, especially when combined
      with gonadotrophin-releasing hormone agonists for ovarian hyperstimulation for in
      vitro fertilization.

PMID- 9286733
TI  - Direct non-genomic effects of follicular steroids on maturing human oocytes:
      oestrogen versus androgen antagonism.
AB  - Previously published data have suggested that oestradiol exerts direct beneficial
      effects on human oocytes during in-vitro maturation and that these effects are at
      least partly due to a non-genomic action of the steroid at the oocyte surface.
      Here we provide evidence showing that a non-genomic effect of oestradiol is
      counteracted by androstenedione. In contrast to these results from in-vitro
      experiments, in which changes in steroid concentrations are abrupt and the non
      genomic responses are rapid, the progressively changing follicular steroid
      concentrations which occur during in-vivo development may rather have permissive
      or restrictive effects on the events of spontaneous oocyte cytoplasmic
      maturation. The oocyte is particularly sensitive at the germinal vesicle stage of
      development to non-genomic steroid actions. Ovarian stimulation protocols should
      thus be adjusted so as to avoid androgen predominance at the mid-follicular
      phase. In patients in whom this condition cannot be met, in-vitro maturation of
      oocytes may be a solution.

PMID- 9286735
TI  - Risk factors for endometriosis in the rhesus monkey (Macaca mulatta): a case
      control study.
AB  - The autopsy records between 1980 and 1995 of 399 female rhesus monkeys (Macaca
      mulatta) at the Wisconsin Regional Primate Research Center were examined.
      Spontaneous endometriosis was found in 81 (20%) of the animals. The mean (+/- SD)
      ages at death for animals with and without endometriosis were 20.7 +/- 5.5 (range
      10-35) and 13.4 +/- 7.7 (range 4-37) years respectively. Many of the animals had
      been exposed to experimental procedures, including laparoscopies, hysterotomies
      and oestradiol implants, and these were examined as possible risk factors for
      endometriosis. Of the 81 affected animals, 62 were matched to unaffected controls
      for age at death (to within 1 year) and year of death (to within 2 years) and the
      effect of various factors on the development of endometriosis was determined
      using conditional logistic regression. Exposure to three or more oestradiol
      implants or one or more hysterotomies were both significant risk factors, with
      estimated relative risks of 9.7 (95% confidence interval 2.5-37.2) and 5.8 (95%
      confidence interval 1.6-20.2) respectively. Animals that had been exposed to one
      or more laparoscopies showed no increased risk for developing endometriosis.
      These findings provide insight into the aetiology of the disease in women. ?2P51
      4RR00167

PMID- 9286736
TI  - Human endometriosis-derived permanent cell line (FbEM-1): establishment and
      characterization.
AB  - A human epithelial-like cell line derived from peritoneal implants from a patient
      with gonadotrophin-releasing hormone (GnRH) agonist-resistant endometriosis
      graded as stage IVd according to the American Fertility Society classification
      was established in vitro. This cell line, designated FbEM-1, exhibited an
      epithelial-like morphology, grew in suspension and was immunoreactive for
      cytokeratins 8, 18, 19, vimentin and human leukocyte class I antigens. The
      cultured cells were negative for various haematopoietic cell markers, including
      the lymphoid cell antigens CD3, CD20 and CD45, von Willebrandt factor,
      carcinoembryonic antigen and the carcinoma antigen-125 (CA-125). In addition, the
      FbEM-1 cells were found to be moderately positive for periodic acid Schiff's
      (PAS) solution but were negative for alpha-naphthyl acetate esterase, peroxidase
      and chloroacetate esterase activities. Using specific antibodies against the
      progesterone, androgen and oestrogen receptors, approximately 40% and 5-10% of
      the cells immunostained for progesterone and androgen receptors respectively,
      while oestrogen receptors were not detected. On cytogenetic analysis using R
      banding, these cells showed numerous chromosomal aberrations, including loss of
      one chromosome X, 4q+, 5q+, trisomy 7,8 and 10 and tetrasomy of chromosomes 17,
      18, 19 and 20. These data show that the continuously growing FbEM-1 cell line
      established from endometriotic implants may be useful in achieving better
      understanding of the histogenesis of endometriosis.

PMID- 9286737
TI  - Polyvinyl alcohol and amino acids as substitutes for bovine serum albumin in
      culture media for mouse preimplantation embryos.
AB  - The effect of replacing bovine serum albumin (BSA) in a simple defined medium
      (KSOM) with polyvinyl alcohol (PVA) and/or amino acids on the percentages of
      mouse zygotes that develop to at least the blastocyst stage and that hatch at
      least partially or completely is reported. Blastocysts could form when BSA was
      replaced with only PVA, but at a moderately reduced rate; however, partial
      hatching, and hence complete hatching, were severely impaired when BSA was
      replaced with only PVA. The substitution of BSA with amino acids alone resulted
      in a high rate of blastocyst formation and moderate impairment of hatching. The
      addition of PVA to BSA-free KSOM supplemented with amino acids had no extra
      effect. BSA had significant effects when added to BSA-free KSOM supplemented with
      amino acids. The BSA caused a significant increase in the rate of partial
      hatching, and may even have had a small effect on the rate of blastocyst
      formation. The results also showed that glucose, at a high concentration of 5.56
      mM, does not inhibit the development of mouse zygotes to hatched blastocysts when
      cultured in KSOM supplemented with amino acids.

PMID- 9286738
TI  - Peptide growth factors and preimplantation development.
AB  - This paper examines some of the problems and questions that must be considered in
      relation to research on the role of growth factors in preimplantation embryos. It
      reviews and summarizes the large body of work on gene expression of growth factor
      receptors and ligands in preimplantation embryos and in oviduct and uterine
      tissue. It also reviews the literature on the effects of gene knockout in
      preimplantation embryos and concludes with a review of work on the effects of
      growth factors on cultured embryos.

PMID- 9286739
TI  - Progestogen intolerance and compliance with hormone replacement therapy in
      menopausal women.
AB  - It is vital that we maximize compliance if patients are to receive the full
      benefits from hormone replacement therapy (HRT). One of the main factors for
      reduced compliance is that of progestogen intolerance. Progestogens have a
      variety of effects apart from the one for which their use was intended, that of
      secretory transformation of the endometrium. Endometrial effects vary between
      individuals and between different progestogens, leading to bleeding problems.
      Symptoms of fluid retention are produced by the sodium-retaining effect on the
      renin-aldosterone system. The nor-testosterone-derived progestogens can have
      adverse effects on skin, lipids, vasculature and insulin resistance. Negative
      mood effects are produced by most progestogens due to the effect on
      neurotransmitters via central nervous system progesterone receptors. Manipulation
      of the dosage and duration of progestogen, continuous administration of a low
      dose of progestogen and a reduction in the number of progestogenic episodes can
      be used to improve compliance. The progestogen and progesterone releasing coils
      and vaginal progesterone gel minimize systemic side effects and bleeding. Adverse
      effects can also be avoided by making use of the progesterone receptor-specific
      progestogens such as the pregnanes (e.g. cyproterone), nor-pregnanes (e.g.
      nomegestrol) and progesterone itself. Hysterectomy remains an option for the
      severely progestogen-intolerant woman. In the future, progestogen intolerance may
      not be an issue if selective oestrogen receptor modulators provide a complete
      alternative to HRT.

PMID- 9286740
TI  - Assisted reproduction practice in Europe: legal and ethical aspects.
AB  - This report describes the ethical and legal aspects of assisted reproductive
      technologies (ART) that have been instituted in European countries. The data were
      collected from questionnaires circulated to fertility centres in 39 countries in
      Europe. Ninety six ART centres were located in 30 of these countries. Nine
      countries do not offer ART services. According to the survey, there are
      approximately 516 centres in Europe, which represent approximately 60% of the
      world ART centres. The survey included information regarding regulation of ART
      services, access to these services, attitude toward genetic material donation,
      cryopreservation of pre-embryos, surrogacy, manipulation of gametes and pre
      embryos, research on pre-embryos and multiple fetal pregnancy reduction. At
      present, the majority of countries in Europe do not have established legislation
      pertaining to the various aspects of ART practice. The study reviews the ethical
      and legal aspects of ART practice in Europe.

PMID- 9286741
TI  - Vitamin C supplementation does not alter the immune response to 2.5 hours of
      running.
AB  - This randomized, double-blind, placebo-controlled study was designed to determine
      the influence of vitamin C supplementation on the immune response to 2.5 hr of
      high-intensity running. Twelve experienced marathon runners (VO2 max 51.6 +/- 1.5
      ml.kg-1.min-1, age 40.5 +/- 2.0 years) were randomized into vitamin C (1,000
      mg/day for 8 days) or placebo groups. On the test day, subjects ran at 75-80% VO2
      max for 2.5 hr, with five blood samples taken before and for 6 hr after. Blood
      samples were analyzed for cortisol and catecholamines; leukocyte subsets;
      interleukin-6; natural killer cell activity; lymphocyte proliferation as induced
      by concanavalin A, phytohemagglutinin, and pokeweed mitogen; and granulocyte
      phagocytosis and activated oxidative burst. Compared with placebo, vitamin C
      supplementation had no significant effect on the pattern of change in any of
      these hormonal or immune measures following 2.5 hr of intensive running.

PMID- 9286742
TI  - The effect of preexercise carbohydrate status on resistance exercise performance.
AB  - The purpose of this study was to determine the effect of a high vs. a low
      preexercise carbohydrate (CHO) diet on performance during multiple sets of
      resistance exercise. Eleven resistance-trained males performed cycle ergometry to
      deplete quadriceps muscle glycogen stores, followed by 48 hr of a high (HICHO) or
      a low (LOCHO) CHO diet. Subjects then performed five sets each of squats, leg
      presses, and knee extensions (resistance = 15 RM) to failure. Blood samples were
      taken before and during exercise for determination of glucose and lactate (LA).
      No differences in performance (repetitions x weight lifted) were observed (HICHO
      = 15,975 +/- 1,381 and LOCHO = 15,723 +/- 1,231 kg). Blood glucose was
      significantly higher after exercise for HICHO compared to LOCHO (HICHO = 4.8 +/-
      0.2 vs. LOCHO = 3.9 +/- 0.2 mmol.L-1). No differences in LA accumulation were
      observed. The data indicated that preexercise CHO status did not affect
      resistance exercise performance. Further, the differences in blood glucose and
      the similarity in LA responses suggest that glycolysis was maintained in the
      LOCHO condition, and there may have been an increased reliance on blood glucose
      when preexercise CHO status was low.

PMID- 9286743
TI  - Does exogenous coenzyme Q10 affect aerobic capacity in endurance athletes?
AB  - The effect of orally supplemented coenzyme Q10 (CoQ10) on plasma CoQ10
      concentration and aerobic capacity in endurance athletes was evaluated. Eighteen
      volunteer male road cyclists and triathletes, 8 in a CoQ10 supplementation group
      (QG) and 10 in a placebo group (PG), successfully completed the experimental
      protocol. Subjects were evaluated during and following graded cycling exercise
      tests, which were performed before and after 28 days of supplementation with 1
      mg.kg-1.day-1 of CoQ10 or placebo. The presupplementation plasma CoQ10
      concentration was significantly increased from 0.91 +/- 0.13 microgram.ml-1 to
      1.97 +/- 0.27 microgram.ml-1 in QG following supplementation (p < .05). However,
      the CoQ10 supplementation regime had no consistently significant effect on oxygen
      uptake, anaerobic and respiratory compensation thresholds, blood lactate, glucose
      and triglyceride kinetics, heart rate, and blood pressure during and after graded
      cycling to exhaustion.

PMID- 9286744
TI  - Preexercise feeding in untrained adolescent boys does not affect responses to
      endurance exercise or performance.
AB  - The effects of preexercise feeding on responses to endurance exercise and
      performance were investigated. Untrained adolescent boys (N = 13, age 14.9 +/-
      0.5 years) completed three endurance test sessions separated by a minimum of 72
      hr. Each session consisted of 75 min of cycling at 60% of VO2 max followed by a
      high-intensity performance test. Dietary conditions were a candy bar (C1: 280
      kcal, 36 g CHO), fat-free fig bars (C2: 200 kcal, 44 g CHO), and a nonnutritive
      sweetened drink (C3: placebo), ingested 10 min prior to exercise. Respiratory
      gases, heart rate, blood glucose, and lactate concentrations were measured
      throughout the test. ANOVA results revealed significant time effects for all
      variables; however, no differences were seen among the conditions. Performance
      times, 311.9 +/- 38.5 s in C1, 316.2 +/- 37.3 s in C2, and 328.1 +/- 46.4 s in
      C3, were not significantly different among conditions. Thus, preexercise feeding
      did not affect responses to endurance exercise or performance in adolescent boys.

PMID- 9286745
TI  - Nutrition beliefs, attitudes, and resource use of high school wrestling coaches.
AB  - Beliefs, attitudes, and nutrition resource use among high school wrestling
      coaches were measured for weight loss, weight class, dehydration, training diet,
      and eating disorders. Most coaches (82%) considered themselves very knowledgeable
      about wrestling but less informed about sport nutrition, weight loss, and vitamin
      supplements. They used a variety of nutrition resources, but only 36% had
      attended nutrition workshops. Almost all coaches were interested in learning more
      about specific nutrition topics. More experienced coaches attended nutrition
      workshops and felt more informed about weight loss and sport nutrition. The mean
      percentage of correct responses to questions about weight loss was 64%, training
      diets 59%, dehydration 57%, body composition 52%, and eating disorders 80%; the
      mean score for healthy attitudes about weight loss was 69%, training diets 34%,
      dehydration 29%, body composition 70%, and eating disorders 69%. These results
      can be used to develop training seminars and educational materials to promote
      greater knowledge and healthy attitudes among wrestling coaches.

PMID- 9286746
TI  - Rate of maturation during the teenage years: nutrient intake and physical
      activity between ages 12 and 22.
AB  - This longitudinal study evaluates the relationship of food intake and physical
      activity with biological maturation of 200 boys and girls during adolescence and
      young adulthood. The subjects were followed during 9 years from ages 12 to 22
      years, with repeated measurements at ages 13, 14, 15, 16, and 21. Biological
      maturation was estimated four times between ages 12 and 17 as skeletal age by
      radiographs of the left hand and wrist. Daily nutritional intake (macro- and
      micronutrients) was assessed with a cross-checked dietary history method. Daily
      physical activity was assessed through structured interview, whereby average
      weekly time spent in activity was used to assign a weighted activity score. The
      107 girls and 93 boys were divided into three maturity groups: early maturers,
      late maturers, and average maturers. It was concluded that in both sexes, late
      maturation seemed to coincide with a higher energetic food intake and a slightly
      higher activity pattern than early maturation during adolescence.

PMID- 9286747
TI  - Calcium for prevention of osteoporotic fractures in postmenopausal women.
AB  - A systematic review of the literature was conducted to assess the effectiveness
      of calcium supplements and/or dietary calcium for the prevention of osteoporotic
      fractures in postmenopausal women. Studies were identified by conducting a
      Medline search using the text words "fracture" and "calcium" for the period 1966
      to March 1997 and by reviewing articles known to the authors. Only studies with
      fracture outcomes were eligible. There were 14 studies of calcium supplements
      (including 4 randomized trials), 18 studies of dietary calcium and hip fracture
      (no randomized trials), and 5 studies of dietary calcium and other fracture sites
      (no randomized trials). The 4 randomized trials of calcium supplements (mean
      calcium dose: 1050 mg) found relative risk (RR) reductions between 25% and 70%.
      Meta-analytic techniques for dose-response data were used to investigate and pool
      the findings of 16 observational studies of dietary calcium and hip fracture.
      These hip fracture studies were not consistent and heterogeneity of study
      findings (p = 0.02) was not easily explained by subject characteristics or study
      design. Pooling study results gave an odds ratio (OR) of 0.96 (95% confidence
      interval, (CI) 0.93-0.99) per 300 mg/day increase in calcium intake (the
      equivalent of one glass of milk). This is likely to be an underestimate of
      calcium's true effect because of inaccurate measurement of dietary calcium in
      observational studies. This review supports the current clinical and public
      health policy of recommending increased calcium intake among older women for
      fracture prevention.

PMID- 9286748
TI  - Parathyroid tumor suppressor on 1p: analysis of the p18 cyclin-dependent kinase
      inhibitor gene as a candidate.
AB  - Loss of chromosome arm 1p DNA is the most common molecular defect thus far
      observed in human parathyroid adenomas, suggesting that 1p is the location of a
      putative tumor suppressor gene (or genes) whose inactivation contributes
      frequently to parathyroid tumorigenesis. To narrow the genomic location of this
      tumor suppressor gene, we analyzed 25 sporadic parathyroid adenomas for allelic
      loss of polymorphic DNA loci on chromosome 1 using 11 microsatellite markers not
      previously scored for this set of tumors. Allelic loss on chromosome arm 1p DNA
      was observed in 8 of 25 adenomas. Marker deletion patterns showed some
      complexity, with the regions most commonly deleted in these tumors being 1p36 and
      1p35-p31. The 1p35-p31 region contains an excellent candidate tumor suppressor
      gene, p18, whose product is a cell cycle regulator that inhibits the cyclin D1
      associated kinase CDK6. Given that cyclin D1 is a parathyroid oncogene,
      inactivation of an inhibitor of cyclin D1 function, like p18, might also cause
      excessive parathyroid growth. To examine the involvement of p18 in parathyroid
      tumorigenesis, we analyzed 25 parathyroid adenomas for mutations of the p18
      coding exons by single strand conformational polymorphism analysis and
      sequencing. No point mutations were found in any of the 25 adenomas. These
      observations indicate that inactivating mutation of the p18 gene occurs
      uncommonly, if at all, in parathyroid adenomas. In addition, the data raise the
      important possibility that more than a single tumor suppressor gene on 1p could
      contribute to parathyroid neoplasia.

PMID- 9286749
TI  - Single-colony derived strains of human marrow stromal fibroblasts form bone after
      transplantation in vivo.
AB  - Populations of marrow stromal fibroblasts (MSFs) can differentiate into
      functional osteoblasts and form bone in vivo. It is not known, however, what
      proportion of MSF precursor cells, colony forming units-fibroblast (CFU-Fs), have
      osteogenic potential. In the present study, analysis of bone formation in vivo by
      single-colony derived strains of human marrow stromal fibroblasts (HMSFs) has
      been performed for the first time. Each strain originated from an individual CFU
      F and underwent four passages in vitro prior to subcutaneous implantation into
      immunodeficient mice within vehicles containing hydroxyapatite-tricalcium
      phosphate ceramic. Multicolony derived HMSF strains were also transplanted to
      serve as positive controls. After 8 weeks, abundant bone formation was found in
      the transplants of all multicolony derived HMSF strains, whereas 20 out of 34
      (58.8%) single-colony derived strains from four donors formed bone.
      Immunostaining with antibody directed against human osteonectin and in situ
      hybridization for human-specific alu sequences demonstrated that cells forming
      new bone were of human origin and were vital for at least 45 weeks post
      transplantation. Both the incidence of bone-forming colonies and the extent of
      bone formation by single-colony derived HMSF strains were increased by
      cultivation with dexamethasone and ascorbic acid phosphate. Other factors,
      including type of transplantation vehicle, morphology, size, and structure of the
      original HMSF colonies showed no obvious correlation with the incidence or extent
      of bone formation. Hematopoietic tissue within the newly formed bone was
      developed in the transplants exhibiting exuberant bone formation. These results
      provide evidence that individual human CFU-Fs have osteogenic potential and yet
      differ from each other with respect to their osteogenic capacity.

PMID- 9286750
TI  - Binding and cyclic AMP stimulation by N-terminally deleted human PTHs (3-84 and 4
      84) in a homologous ligand receptor system.
AB  - We have produced in yeast two human parathyroid hormone (hPTH) analogs with amino
      terminal deletions, hPTH(3-84) and hPTH(4-84), employing the mating factor alpha
      (MF alpha) expression system. The authenticity of the polypeptides was
      demonstrated by amino-terminal analysis, amino acid composition, and molecular
      mass analysis. In cells (LLC-PK1) transfected with the human PTH/parathyroid
      hormone-related protein (PTHrP) receptor, using [125I-Tyr36]chickenPTHrP(1-36)NH2
      as radioligand, binding studies revealed dissociation constants at equilibrium
      (Kd) for hPTH(3-84) and hPTH(4-84) of 4.7 and 8.0 nM, respectively, only slightly
      higher than natural recombinant hPTH(1-84) Kd = 2.3 nM). In comparison,
      [Nle8,18,Tyr34]bovinePTH(3-34)NH2 and [Tyr36]cPTHrP(1-36)NH2 showed equal Kd's of
      1.9 nM. Neither of the N-terminally deleted hPTH analogs showed any detectable
      stimulation of cAMP production in the cells at concentrations below 20 nM. At
      supersaturated concentrations (500 nM) with receptor occupancy of more than 95%
      these hPTH analogs revealed about 15% rest agonism compared with that of hPTH(1
      84). hPTH(1-84) and [Tyr36]cPTHrP(1-36)NH2 showed an equal half maximal cyclic
      adenosine monophosphate (cAMP) stimulation of about 0.8 and 0.7 nM, respectively.
      The hPTH analogs did not show any ability to antagonize cellular cAMP production
      induced by either hPTH or [Tyr36]cPTHrP(1-36)NH2. [Nle8,18,Tyr34]bPTH(3-34)NH2
      did also not antagonize cAMP stimulation by hPTH, but inhibited [Tyr36]cPTHrP(1
      36)NH2-induced cAMP production by 40% when present at a 1000 M excess. These
      distinct results related to PTH and PTHrP from different species are important to
      consider in experiments evaluating potential hPTH or PTHrP antagonism, and
      employment of a hPTH/PTHrP receptor model is a requirement.

PMID- 9286752
TI  - Articular chondrocytes produce factors that inhibit maturation of sternal
      chondrocytes in serum-free agarose cultures: a TGF-beta independent process.
AB  - Under normal conditions, articular chondrocytes persist throughout postnatal
      life, whereas "transient" chondrocytes, which constitute the bulk of prenatal and
      early postnatal cartilaginous skeleton, undergo maturation, hypertrophy, and
      replacement by bone cells. The mechanisms regulating the markedly different
      behavior and fate of articular and transient chondrocytes are largely unclear. In
      the present study, we asked whether articular chondrocytes possess dominant
      antimaturation properties which may subtend their ability to persist throughout
      life. Adult chicken articular chondrocytes and transient maturing chondrocytes
      from the core region of day 17, chick embryo cephalic sternum were cultured or
      cocultured in serum-free agarose conditions. When the sternal cells were grown by
      themselves, they quickly developed into hypertrophic type X collagen-synthesizing
      cells; however, when they were cocultured with as few as 10% articular
      chondrocytes or fed with articular chondrocyte-conditioned medium, their
      maturation was markedly impaired, as revealed by a sharp drop in type X collagen
      synthesis. A similar, albeit less potent, antimaturation activity characterized
      resting and proliferating immature chondrocytes isolated from other regions of
      embryonic sternum. Transforming growth factor-beta 2 (TGF-beta 2) was previously
      suggested to be an inhibitor of chondrocyte maturation. We found, however, that
      treatment with a neutralizing antiserum to TGF-beta did not counteract the
      inhibition of maturation in cocultures of articular and maturing core sternal
      chondrocytes. Indeed, articular chondrocytes produced and accumulated relatively
      low levels of TGF-beta in their culture medium, about 15 ng/ml/48 h, of which
      over 90% was latent; surprisingly, maturing sternal core chondrocytes accumulated
      over 10-fold more TGF-beta in the medium, about 150 ng/ml/48 h, of which over 20%
      was endogenously active. These results indicate that articular chondrocytes do
      possess dominant antimaturation properties which appear to be TGF-beta
      independent. The TGF-beta s may thus have a more prominent role in the terminal
      phases of chondrocyte maturation, as indicated by their abundance and greater
      activity in hypertrophic chondrocytes.

PMID- 9286751
TI  - Clodronate and liposome-encapsulated clodronate are metabolized to a toxic ATP
      analog, adenosine 5'-(beta, gamma-dichloromethylene) triphosphate, by mammalian
      cells in vitro.
AB  - Clodronate, alendronate, and other bisphosphonates are widely used in the
      treatment of bone diseases characterized by excessive osteoclastic bone
      resorption. The exact mechanisms of action of bisphosphonates have not been
      identified but may involve a toxic effect on mature osteoclasts due to the
      induction of apoptosis. Clodronate encapsulated in liposomes is also toxic to
      macrophages in vivo and may therefore be of use in the treatment of inflammatory
      diseases. It is generally believed that bisphosphonates are not metabolized.
      However, we have found that mammalian cells in vitro (murine J774 macrophage-like
      cells and human MG63 osteosarcoma cells) can metabolize clodronate
      (dichloromethylenebisphosphonate) to a nonhydrolyzable adenosine triphosphate
      (ATP) analog, adenosine 5'-(beta, gamma-dichloromethylene) triphosphate, which
      could be detected in cell extracts by using fast protein liquid chromatography.
      J774 cells could also metabolize liposome-encapsulated clodronate to the same ATP
      analog. Liposome-encapsulated adenosine 5'-(beta, gamma-dichloromethylene)
      triphosphate was more potent than liposome-encapsulated clodronate at reducing
      the viability of cultures of J774 cells and caused both necrotic and apoptotic
      cell death. Neither alendronate nor liposome-encapsulated alendronate were
      metabolized. These results demonstrate that the toxic effect of clodronate on
      J774 macrophages, and probably on osteoclasts, is due to the metabolism of
      clodronate to a nonhydrolyzable ATP analog. Alendronate appears to act by a
      different mechanism.

PMID- 9286753
TI  - Assessment of articular cartilage and subchondral bone: subtle and progressive
      changes in experimental osteoarthritis using 50 MHz echography in vitro.
AB  - The main objectives of this work were to demonstrate the potential of 50 MHz
      echography for assessing initial and progressive morphological and structural
      changes of articular cartilage and bone developed in an experimental model of
      osteoarthritis (OA). Degenerative lesions were induced in rat knees by the
      unilateral intra-articular injection of a 3 mg dose of mono-iodo-acetic acid. To
      assess the lesion progression, the animals (n = 30) were sacrificed at different
      time intervals up to 8 weeks after the injection. Three-dimensional echographic
      data were acquired in vitro on patellar cartilage and bone at various stages of
      the remodeling process using a scanning ultrasound microscope. Changes involving
      the OA cartilage characteristics are discussed relative to those of the
      contralateral control joint which received a placebo. Images of control cartilage
      showed a smooth hyperechoic articular surface and an echoic matrix. The cartilage
      thickness was 266 +/- 44 microns (mean +/- SD) in the central region of the
      tissue. The precision of ultrasonic thickness measurements was better than 1.3%.
      First changes in cartilage internal structure and subchondral bone appeared on
      ultrasound images 3 days after the injection and were even more evident by day 7.
      They resulted in a slight thinning of the cartilage, a 30% increase of its
      internal structure echogenicity, and the appearance of echoic zones in
      subchondral bone. Histologic findings confirmed chondrocyte depletion and
      degeneration, decrease of matrix proteoglycans, and fibrovascular connective
      tissue proliferation at the subchondral plate. Progressive and severe lesions at
      both bone and cartilage surface and internal structure were assessed and
      correlated to histologic features. These results show that high resolution
      echography is sensitive to subtle and progressive osteochondral remodeling. This
      technique has the potential to be used for intra-articular quantitative imaging
      and assessment of early changes in bone and cartilage structure associated with
      natural human disease.

PMID- 9286754
TI  - Macrophage colony stimulating factor down-regulates MCSF-receptor expression and
      entry of progenitors into the osteoclast lineage.
AB  - Macrophage colony-stimulating factor (MCSF), although necessary for entry of
      precursors into the early preosteoclast pathway, inhibits osteoclastogenesis at
      high doses. To clarify the relationship between MCSF and osteoclast formation, we
      investigated the effect of exogenous MCSF in murine bone marrow culture.
      Precursor proliferation and the expression of MCSF-receptor were examined after 4
      days of culture in the presence or absence of accessory stromal cells. In both
      mixed marrow and destromalized cell cultures, exogenous MCSF dose-dependently
      decreased 125I-MCSF binding (by 65 +/- 5.0% at 3500 and 87 +/- 16.7% at-7000
      U/ml, respectively) while enhancing mononuclear cell proliferation after 3 days
      of exposure (by 2.8- and 6.3-fold, respectively). These effects were maintained
      24 h after removal of exogenous MCSF and, as such, likely represented an MCSF
      induced change in MCSF receptor-bearing cells. Exposure to exogenous MCSF (3500
      U/ml) days 2-4 dose-dependently inhibited tartrate resistant acid phosphatase
      positive multinuclear cell (TRAP+ MNC) formation counted at the end of day 7, by
      64.3 +/- 4.1%. This inhibition of TRAP+ MNC formation was preceded by a 92 +/- 9%
      decrease in the expression of carbonic anhydrase II mRNA measurable at 4 days.
      These results indicate that MCSF promotes proliferation of a population of cells
      expressing lower cognate receptor sites. Changes in MCSF-receptor expression
      appear to modulate the final lineage selection of the pluripotent monoblastic
      progenitor.

PMID- 9286755
TI  - Peptide aldehyde inhibitors of cathepsin K inhibit bone resorption both in vitro
      and in vivo.
AB  - We have shown previously that cathepsin K, a recently identified member of the
      papain superfamily of cysteine proteases, is expressed selectively in osteoclasts
      and is the predominant cysteine protease in these cells. Based upon its abundant
      cell type-selective expression, potent endoprotease activity at low pH and
      cellular localization at the bone interface, cathepsin K has been proposed to
      play a specialized role in osteoclast-mediated bone resorption. In this study, we
      evaluated a series of peptide aldehydes and demonstrated that they are potent
      cathepsin K inhibitors. These compounds inhibited osteoclast-mediated bone
      resorption in fetal rat long bone (FRLB) organ cultures in vitro in a
      concentration-dependent manner. Selected compounds were also shown to inhibit
      bone resorption in a human osteoclast-mediated assay in vitro. Chz-Leu-Leu-Leu-H
      (in vitro enzyme inhibition Ki,app = 1.4 nM) inhibited parathyroid hormone (PTH)
      stimulated resorption in the FRLB assay with an IC-50 of 20 nM and inhibited
      resorption by isolated human osteoclasts cultured on bovine cortical bone slices
      with an IC-50 of 100 nM. In the adjuvant-arthritic (AA) rat model, in situ
      hybridization studies demonstrated high levels of cathepsin K expression in
      osteoclasts at sites of extensive bone loss in the distal tibia. Cbz-Leu-Leu-Leu
      H (30 mg/kg, intraperitoneally) significantly reduced this bone loss, as well as
      the associated hind paw edema. In the thyroparathyriodectomized rat model, Cbz
      Leu-Leu-Leu-H inhibited the increase in blood ionized calcium induced by a 6 h
      infusion of PTH. These data indicate that inhibitors of cathepsin K are effective
      at reducing osteoclast-mediated bone resorption and may have therapeutic
      potential in diseases of excessive bone resorption such as rheumatoid arthritis
      or osteoporosis.

PMID- 9286756
TI  - Decreased beta-isomerization of the C-terminal telopeptide of type I collagen
      alpha 1 chain in Paget's disease of bone.
AB  - In Paget's disease of bone, the normal lamellar bone is replaced by a woven
      structure with an irregular arrangement of collagen fibers. In this study, we
      investigated whether the degree of beta-isomerization within C-telopeptide of
      alpha 1 chain of type I collagen was altered in Paget's disease compared with
      other bone diseases with no alteration of bone structure. In Paget's disease (n =
      26), but not in patients with primary hyperparathyroidism (n = 6) or
      hyperthyroidism (n = 17), the urinary excretion of nonisomerized (alpha)
      fragments derived from degradation of type I collagen C-telopeptide (CTX) was
      markedly increased compared with beta-isomerized CTX (+ 13-fold vs. + 3.5-fold
      over controls) resulting in an urinary alpha CTX/beta CTX ratio 3-fold higher
      than in controls (2.6 +/- 1.0 vs. 0.8 +/- 0.3, p < 0.001). In five pagetic
      patients in complete remission, as demonstrated by normal total alkaline
      phosphatase activity, the alpha CTX/beta CTX ratio was normal. The
      immunohistochemistry of normal and pagetic human bone sections showed a
      preferential distribution of alpha CTX within woven structure, while lamellar
      bone was intensely stained with an anti-beta CTX antibody, suggesting a lower
      degree of beta-isomerization of type I collagen in the woven pagetic bone. In
      collagenase digest of human bone specimens, we found a lower proportion of beta
      isomerized type I collagen molecules in pagetic bone (40% of beta CTX) than in
      normal bone taken from trabecular (68%) and cortical compartments (71%). In
      conclusion, we found that in Paget's disease the alpha CTX/beta CTX ratio in bone
      and in urine is markedly increased. This altered beta isomerization can be
      accurately detected in vivo by measuring urinary degradation products arising
      from bone resorption.

PMID- 9286757
TI  - Aromatase in human bone tissue.
AB  - Peripheral aromatization of androgens exert estrogenic actions in many tissues.
      Recently in situ production of estrogens by aromatase was detected in human bone
      and cultured osteoblasts and has been proposed to participate in the maintenance
      of bone mass. We examined aromatase expression by immunohistochemistry and mRNA
      in situ hybridization in 16 cases of tibia (female 2 male, 14 female, 62 +/- 5.2
      years old) and quantified the level of aromatase mRNA in 28 cases of rib, femur,
      and lumbar vertebrae (16 male, 12 female, 58.0 +/- 11.3 years old) by reverse
      transcriptase-polymerase chain reaction (RT-PCR) in order to study whether or not
      and in which cell types aromatase was expressed in human bone tissues. We also
      studied alternative use of multiple exons 1 of its gene and immunolocalization of
      type I 17 beta-hydroxysteroid dehydrogenase (HSD), which converts estrone
      produced by aromatase to estradiol. Strong aromatase immunoreactivity and mRNA
      hybridization as well as type I 17 beta-HSD immunoreactivity were detected in
      lining cells, osteoblasts, chondrocytes of articular cartilage, and adipocytes
      adjacent to bone trabeculae in all the cases examined. Amounts of aromatase mRNA
      varied greatly among the subjects (11.25 +/- 9.77, 0.61-42.84 attomol/ng of total
      RNA). The amount of aromatase expression was not correlated with age or gender of
      the subjects but positively correlated with the degree of osteroporotic changes
      evaluated by radiological findings of lumbar vertebrae. Analysis of multiple
      exons 1 revealed that 1b or fibroblast type was predominantly (23/26) utilized as
      a promoter of aromatase gene expression. These results demonstrated that
      aromatase is expressed widely in human bone tissue and may play important roles
      in maintenance of human bone tissue.

PMID- 9286758
TI  - Enhancement by sex hormones of the osteoregulatory effects of mechanical loading
      and prostaglandins in explants of rat ulnae.
AB  - Explants of ulnae from 5-week-old male and female rats were cleaned of marrow and
      soft tissue and, in the presence and absence of 10(-8) M 17 beta-estradiol (E2)
      or 5 alpha-dihydrotestosterone (DHT), mechanically loaded or treated with
      exogenous prostanoids previously shown to be produced during loading. Over an 18
      h period, mechanical loading (peak strain 1300 mu epsilon, 1 Hz, 8 minutes,
      maximum strain rate 25,000 mu epsilon/s), prostaglandin E2 (PGE2) and
      prostacyclin (PGI2) (10(-6) M), each separately produced quantitatively similar
      increases in cell proliferation and matrix production in bones from males and
      females, as indicated by incorporation of [3H]thymidine into DNA and [3H]proline
      into collagen. E2 and DHT both increased [3H]thymidine and [3H]proline
      incorporations, E2 producing greater increases in females than in males.
      Indomethacin abrogated the effects of loading, but had no effects on those of sex
      hormones. Loading, or prostanoids, together with sex hormones, produced responses
      generally equal to or greater than the addition of the individual influences
      acting independently. In females there was a synergistic response in
      [3H]thymidine incorporation between loading and E2, which was quantitatively
      similar to the interaction between E2 and PGE2 or PGI2. The interaction between
      loading and E2 for [3H]proline incorporation was not mimicked by these
      prostanoids. In males the synergism in [3H]proline incorporation seen between
      loading and DHT was mimicked by that between PGI2 and DHT. We conclude that
      loading stimulates increased bone cell proliferation and matrix production in
      situ through a prostanoid-dependent mechanism. This response is equal in size in
      males and females. Estrogen and testosterone increase proliferation and matrix
      production through a mechanism independent of prostanoid production. The
      interactions between loading and hormones are reproduced in some but not all
      cases by E2 and prostaglandins. E2 with loading and prostaglandins has greater
      effects in female bones, while DHT with loading and prostaglandins has greater
      effects in males.

PMID- 9286759
TI  - Effects of dihydrotestosterone on bone biochemical markers in sham and
      oophorectomized rats.
AB  - Evidence exists to suggest that androgens stimulate bone formation in the
      estrogen-deficient state, however the mechanism of action is unclear. The
      following study investigates the effect of dihydrotestosterone (DHT) on
      biochemical markers of bone turnover and calcium homeostasis in sham and
      oophorectomized (oophx) rats when either vehicle, 40, 80, or 160 mg/kg body
      weight (bw) DHT were administered at the time of operation or at 15 weeks
      postoperation. Serum alkaline phosphatase (ALP) increased following DHT
      administration in sham and oophx rats in all groups (mean ALP +/- SEM [U/l] week
      8; sham vehicle, 40 +/- 7; sham 160 mg DHT/kg bw, 72 +/- 5; oophx vehicle, 60 +/-
      6; oophx 160 mg DHT/kg bw, 88 +/- 11) (p < 0.001). In contrast, serum osteocalcin
      was significantly suppressed in oophx rats administered DHT 15 weeks following
      operation (mean osteocalcin +/- SEM [micrograms/l] week 8; oophx vehicle, 17.6 +/
      3.5; oophx 160 mg DHT/kg bw, 10.5 +/- 1) (p < 0.01). Urine deoxypyridinoline was
      significantly decreased when DHT was administered 15 weeks postoophorectomy (p <
      0.001); however, urine hydroxyproline was not affected by DHT treatment in any
      group. Urine calcium was decreased by DHT treatment (mean Ca/Cr +/- SEM week 8;
      sham vehicle, 0.87 +/- 0.13; sham 160 mg DHT/kg bw, 0.24 +/- 0.08; oophx vehicle,
      0.68 +/- 0.16; oophx 160 mg DHT/kg bw; 0.45 +/- 0.1) (p < 0.005) which was
      associated with an increase in the renal tubular reabsorption of calcium (p <
      0.05). This study demonstrates the direct effects of DHT on both bone cell
      activities and the renal handling of calcium.

PMID- 9286760
TI  - Association of bone mineral density with apolipoprotein E phenotype.
AB  - The phenotypes of apolipoprotein E (Apo E) and their relationship with the bone
      mineral density (BMD) were examined in 284 unrelated postmenopausal Japanese
      women aged 47-82 years (64.0 +/- 1.0 years, mean +/- SE). The Apo E phenotype was
      analyzed by the isoelectric focusing method, followed by immunoblotting. The
      relationship between the Apo E phenotype and the vitamin D receptor (VDR) gene or
      estrogen receptor (ER) gene genotypes was also studied in the same population.
      The Apo E phenotypic frequencies in our population were 9.9% for E3/2, 66.5% for
      E3/3, 1.8% for E4/2, 19.7% for E4/3, and 2.1% for E4/4. We classified these
      phenotypes into three categories: Apo E4-/- (E3/2 and E3/3, n = 217, Apo E4 +/-
      (E4/3 and E4/2, n = 61), and Apo E4+/+ (E4/4, n = 6). The age, body weight, body
      height, and years since menopause were not significantly different among these
      three categories. The lumbar BMD values in these three groups were significantly
      different in the order of E4-/- (0.91 +/- 0.01 g/cm2), E4 +/- (0.85 +/- 0.02
      g/cm2), and E4+/+ (0.83 +/- 0.06 g/cm2) (p = 0.031). The same trend was also
      observed for the Z score of the total BMD (p = 0.022). The serum level of intact
      osteocalcin in E4+/+ (15.2 +/- 5.7 ng/ml) was higher than in E4-/- (7.7 +/- 0.3
      ng/ml) or E4 +/- (7.7 +/- 0.7 ng/ml) (p = 0.004 by analysis of variance).
      However, there were no other significant differences in the serum or urinary
      levels of bone turnover markers. Serum cholesterol in the E4+/+ group tended to
      be higher than in the other two groups (p = 0.05). There were no significant
      associations of the VDR and ER genotypes with the Apo E4 phenotype. A
      multivariate linear regression analysis revealed Apo E4 to be a significant,
      independent predictor of the Z score of the lumbar BMD. The effect of the Apo E4
      allele on the Z score of the lumbar BMD (-0.493 +/- 0.152) was not significantly
      different from that in the AAB of VDR (-0.616 +/- 0.225) or PPxx of ER (-0.785 +/
      0.314). In conclusion, the Apo E4 allele is associated with a low bone mass in
      postmenopausal Japanese.

PMID- 9286761
TI  - Vitamin D receptor gene polymorphisms, bone turnover, and rates of bone loss in
      older African-American women.
AB  - Bone mineral density (BMD) is under genetic control. Some studies in Caucasian
      and Asian women suggest that polymorphisms in the vitamin D receptor (VDR) gene
      are associated with BMD and the rate of postmenopausal bone loss. We determined
      if similar associations exist in 101 African-American women aged 65 years and
      older (71 +/- 5 years, mean +/- SD). We also examined the relation between VDR
      genotype and fractional 45Ca absorption and markers of bone formation
      (osteocalcin) and resorption (N-telopeptides) in these women. BMD was measured at
      the proximal femur and whole body at baseline and after 1.9 +/- 0.4 years (femur
      only) on a Hologic QDR-2000 densitometer using dual-energy X-ray absorptiometry.
      Calcaneal BMD was measured with single x-ray absorptiometry. VDR gene
      polymorphisms were defined by the endonucleases BsmI, ApaI, and TaqI. These
      polymorphisms were not associated with BMD at any skeletal site or with markers
      of bone turnover. There was a significant interaction between age and VDR
      genotype where the oldest women (> 70 years) with the TT genotype experienced
      greater hip bone loss than women with the TT genotype (-2.1%/year vs. -0.4%/year,
      respectively), whereas heterozygous women experienced an intermediate rate of
      bone loss (-1.3%/year). Women homozygous for the B allele had 14% lower
      fractional 45Ca absorption compared with women homozygous for the b allele,
      although this difference was not statistically significant (p = 0.08). We
      conclude that VDR gene polymorphisms are not associated with BMD or indices of
      bone turnover in this population of older African-American women. However, DNA
      sequence variation in the VDR gene or a nearby locus may influence intestinal
      calcium transport and the rate of postmenopausal bone loss in African-American
      women.

PMID- 9286762
TI  - Prospective ten-month exercise intervention in premenarcheal girls: positive
      effects on bone and lean mass.
AB  - Enhancement of bone mineral acquisition during growth may be a useful preventive
      strategy against osteoporosis. The aim of this study was to explore the lean
      mass, strength, and bone mineral response to a 10-month, high-impact, strength
      building exercise program in 71 premenarcheal girls, aged 9-10 years. Lean body
      mass, total body (TB), lumbar spine (LS), proximal femur (PF), and femoral neck
      (FN) bone mineral were measured using the Hologic QDR 2000+ bone densitometer.
      Strength was assessed using a grip dynamometer and the Cybex isokinetic
      dynamometer (Cybex II). At baseline, no significant difference in body
      composition, pubertal development, calcium intake, physical activity, strength,
      or bone mineral existed between groups. At completion, there were again no
      difference in height, total body mass, pubertal development, calcium intake, or
      external physical activity. In contrast, the exercise group gained significantly
      more lean mass, less body fat content, greater shoulder, knee and grip strength,
      and greater TB, LS, PF, and FN BMD (exercise: TB 3.5%, LS 4.8%, PF 4.5%, and FN
      12.0%) compared with the controls (controls: TB 1.2%, LS 1.2%, PF 1.3%, and FN
      1.7%). TB bone mineral content (BMC), LS BMC, PF BMC, FN BMC, LS bone mineral
      apparent density (BMAD), and FN bone area also increased at a significantly
      greater rate in the exercise group compared with the controls. In multiple
      regression analysis, change in lean mass was the primary determinant of TB, FN,
      PF, and LS BMD accrual. Although a large proportion of bone mineral accrual in
      the premenarcheal skeleton was related to growth, an osteogenic effect was
      associated with exercise. These results suggest that high-impact, strength
      building exercise is beneficial for premenarcheal strength, lean mass gains, and
      bone mineral acquisition.

PMID- 9286763
TI  - Universal standardization of bone density measurements: a method with optimal
      properties for calibration among several instruments.
AB  - The International Dual-Photon X-Ray Absorptiometry (DXA) Standardization
      Committee (IDSC) conducted a cross-calibration study among three models of DXA
      machines from three different manufacturers. In that study, 100 subjects were
      scanned on all three machines. A set of equations were derived to convert bone
      mineral density (BMD) on each machine to a "standardized BMD" (sBMD) such that
      sBMD from the same subject derived from different machines would be approximately
      the same. In a reanalysis of the cross-calibration data, we showed that the
      conversion method used in the IDSC study did not achieve several optimal
      properties desirable in such conversions. We derived new conversion equations to
      sBMD based on minimizing differences among sBMD from the three machines. More
      important is that the new conversions have no residual bias that was present in
      the IDSC conversions. The performance of the methods were compared on the cross
      calibration data as well as an external data set. We conclude that the IDSC
      conversions are adequate for clinical use on other machines worldwide, but that
      researchers should standardize their own machines in a laboratory using the new
      method.

PMID- 9286764
TI  - Site of osteodensitometry in perimenopausal women: correlation and limits of
      agreement between anatomic regions.
AB  - Because the bone mineral density (BMD) in different anatomic regions is
      heterogenous the number of women who fulfill the World Health Organization
      definition of osteopenia or osteoporosis increases with the number of regions
      examined. The purpose of this study was to investigate the agreement between
      measurements of the spine, femur, forearm, and whole body following menopause.
      Two thousand and five healthy, perimenopausal women, mean age 50.6 years, were
      studied using Hologic QDR-1000/W and QDR-2000 densitometers. Though the BMD of
      different anatomic regions were correlated (r = 0.40-0.77, p < 0.01), the
      variability in each patient regarding T and Z scores between regions was
      considerable. For example, despite a high correlation (r = 0.67, p < 0.01) and no
      systematic difference between the T scores for total femoral and lumbar BMD, the
      limits of agreement (mean difference +/- 2 SD) for the comparison were -1.89 to
      1.87. Femoral neck T scores were 0.5 SD lower than those of the other regions,
      confirming reports that the young adult reference for this measurement is
      disproportionally high. The prevalence of osteoporosis was 1.2% when femur total
      BMD was considered alone and 5.9% when lumbar and ultradistal forearm results
      were included. However, as many as 7.9% showed osteoporosis of the femoral neck
      when the Hologic T score was used, compared with 0.7% using National Health and
      Nutrition Examination Survey (NHANES) values. The choice of anatomic region and
      availability of appropriate young adult reference data has considerable impact on
      the apparent prevalence of osteoporosis. Given the heterogeneity between regions,
      a combination of spinal and femoral densitometry should be used in diagnosing
      osteoporosis, though this increases the prevalence of osteoporosis by 50% or more
      in perimenopausal women.

PMID- 9286765
TI  - Five jumps per day increase bone mass and breaking force in rats.
AB  - The effects of jump training on bone morphological and mechanical properties were
      investigated in immature bones of female Fischer 344 rats. Five-week-old rats
      were divided into control or five jump-trained groups comprised of 5-, 10-, 20-,
      40-, and 100-jump groups, representing the number of jumps per day. The rats were
      jump-trained 5 days/week for 8 weeks, and the height of jump was increased to 40
      cm progressively. The femur and tibia in the 5-jump group had significantly
      greater fat-free dry weights per body weight and maximum loads at the fracture
      tests than those in the control group. The tibia in the 5-jump group also had
      significantly larger cortical area at the cross-sectional analysis. Although a
      slight tendency toward increase according to the number of jumps per day was
      observed, there were few differences in bone morphological and mechanical
      parameters among the 10-, 20-, and 40-jump groups. The present results indicate
      that a large number of strains per day is not necessary for bone hypertrophy to
      develop in rats.

PMID- 9286766
TI  - Reduced bone mass in Dutch adolescents fed a macrobiotic diet in early life.
AB  - This study investigated the effect of a macrobiotic (vegan-type) diet, low in
      calcium and vitamin D, consumed in early life, on bone mineral during
      adolescence. Bone mineral content (BMC) and bone area were measured in 195
      adolescents (103 girls, 92 boys) aged 9-15 years, using dual-energy X-ray
      absorptiometry. Ninety-three adolescents (43 girls, 50 boys) had followed a
      macrobiotic diet in childhood, and 102 (60 girls, 42 boys) were control subjects.
      After adjustment for bone area, weight, height, percent body lean, age, and
      puberty, BMC was significantly lower in macrobiotic subjects, in boys and girls,
      respectively, at the whole body, -3.4% and -2.5%, spine, -8.5% and -5.0%, femoral
      neck, -8.0% and -8.2%, midshaft radius, -6.8% and -5.6%, and also in girls, at
      the trochanter, -5.8% (p < 0.05). No group differences were observed at the
      wrist. Group differences were not explained by current calcium adjusted bone mass
      at age 9-15 years, observations which may hold important implications for
      fracture risk in later life.

PMID- 9286767
TI  - The effects of smoking on bone mass and the rates of bone loss among elderly
      Japanese-American men.
AB  - Bone density and bone loss rates were examined among Japanese-American men
      categorized as current cigarette smokers, past smokers, and nonsmokers. The
      design included a retrospective study of smoking and bone density and a
      prospective study of current smoking and bone loss rates. The mean length of
      follow-up was 5 years; the setting was the island of Oahu. The subjects included
      1303 men in the Hawaii Osteoporosis Study, 51-82 years old at their initial
      examination. Twenty percent were current smokers, 45% past smokers, and 35% had
      never smoked. Their bone density was measured at the distal and proximal radius
      and calcaneus using single photon absorptiometry. Compared with never smokers,
      current and past smokers had significantly lower bone density, especially in the
      predominantly cancellous calcaneus (4.8 and 4.3% lower, respectively) and
      partially trabecular distal radius (1.8 and 3.3% lower, respectively). The
      magnitude of the smoking effect was linked strongly to the duration of smoking
      and also to the number of cigarettes smoked. Bone loss rates subsequent to the
      initial measurement were greater in the current smokers than the never smokers
      (20.5, 27.2, and 9.7% greater at the calcaneus, distal, and proximal radius,
      respectively) but the differences did not achieve significance. Smokers of more
      than one pack per day had 32.0, 77.6, and 30.7% greater loss rates than never
      smokers in these same sites; the difference achieved significance at the distal
      radius. The results from the distal radius suggest that these smokers may
      increase their fracture risk 10-30% per decade of smoking. The adverse effects of
      smoking appeared to be greater in cancellous than cortical bone.

PMID- 9286769
TI  - The interaction of PCP and HAp in vivo.

PMID- 9286768
TI  - Tumor-induced osteomalacia: clinical and basic studies.
AB  - A patient with classic clinical and biochemical features of tumor-induced
      osteomalacia (hypophosphatemia, phosphaturia, and undetectable serum
      concentrations of 1,25-dihydroxyvitamin D [1,25(OH)2D]) was studied before and
      after resection of a benign extraskeletal chondroma from the plantar surface of
      the foot. Presurgical laboratory evaluation was notable for normal serum
      concentrations of calcium, intact parathyroid hormone (PTH), parathyroid hormone
      related protein (PTHrP), and osteocalcin, increased serum alkaline phosphate
      activity, and frankly elevated urinary cyclic adenosine monophosphate (cAMP) and
      pyridinium cross-link excretion. Quantitative histomorphometry showed severe
      osteomalacia and deep erosions of the cancellous surface by active osteoclasts.
      After resection, serum 1,25(OH)2D normalized within 24 h, while renal tubular
      phosphorus reabsorption and serum phosphorus did not normalized until days 2 and
      3, respectively; serum Ca declined slightly, and serum intact PTH, osteocalcin,
      and urinary pyridinium cross-link excretion increased dramatically. Urinary cAMP
      excretion declined immediately after resection and then began to increase
      concomitant with the increase in serum intact PTH. A second bone biopsy taken 3
      months after resection demonstrated complete resolution of the osteomalacia,
      increased mineral apposition rate (1.09 mu/day), resorption surface (9.2%),
      mineralizing surface (71%), and bone formation rate (0.83 mm3/mm2/day), and
      marked decrease in cancellous bone volume (13.1%) and trabecular connectivity
      compared with first biopsy. Tumor extracts did not affect phosphate transport in
      renal epithelial cell lines or 1 alpha-hydroxylase activity in a myelomonocytic
      cell line. The patient's course suggests that the normal 1,25(OH)2D and
      phosphorus metabolism is due to a tumor product that may be acting via
      stimulation of adenylate activity. Increased bone resorption prior to surgical
      resection suggests that the tumor may also produce an osteoclast activator. The
      rise in resorption surface and pyridinium cross-link excretion, increase in serum
      osteocalcin and bone mineralization, normalization of osteoid width, and fall in
      cancellous bone volume after resection are consistent with healing of
      osteomalacia by rapid remodeling.

PMID- 9286770
TI  - Pharmacokinetic, hemodynamic, and metabolic effects of cyclosporine sandimmune
      versus the microemulsion neoral in heart transplant recipients.
AB  - BACKGROUND: Cyclosporine is a potent immunosuppressive agent that is, however,
      associated with systemic hypertension and renal dysfunction. The purpose of this
      investigation was to study the pharmacokinetic and long-term renal and
      hypertensive effects of Sandimmune (Sandoz) versus the new Neoral (Novartis)
      formulation of cyclosporine in heart transplant recipients. METHODS: Twenty heart
      transplant recipients with stable conditions and aged 54 +/- 9 years were studied
      in an open-labeled single-arm conversion protocol. Twelve-hour pharmacokinetic
      studies were performed on Sandimmune and after 4 weeks of treatment with Neoral
      at similar dosage. The 24-hour blood pressure monitoring, creatinine clearance,
      and complete biochemistry profile were studied simultaneously to the
      pharmacokinetic studies. Six-month follow-up with serial measurements of
      cyclosporine levels, and biochemistry profile was completed. RESULTS: Conversion
      to Neoral resulted in a 24% increase in area-under-the-curve in spite of no
      significant changes in cyclosporine trough levels (165 +/- 48 [Sandimmune] vs 169
      +/- 32 nmol/L; p = 0.26). Respectively, 16%, 68%, and 16% were poor, average, and
      good absorbers on Sandimmune versus 26% and 74% being average or good absorbers
      on Neoral. Averaged systolic and diastolic blood pressure were not affected by
      Neoral, but blood pressure readings increased in 20% of patients previously known
      as having hypertension. The 24-hour blood pressure data yielded no significant
      changes with Neoral, but the nocturnal drop in systolic blood pressure was
      attenuated by Neoral. Twenty-four-hour creatinine clearance was not affected by
      Neoral, but serum magnesium levels decreased significantly at 6 months.
      CONCLUSIONS: Neoral resulted in 24% increase in cyclosporine exposure without
      significant changes in trough levels, and improved absorption status. This
      greater drug exposure is well tolerated and resulted in a slight increase in
      blood pressure in a subset of patients and some decrease in magnesium levels, but
      it had no effect on renal function.

PMID- 9286771
TI  - Tacrolimus: a superior agent to OKT3 for treating cases of persistent rejection
      after intrathoracic transplantation.
AB  - Acute myocardial rejection refractory to treatment still contributes
      significantly to patient death after intrathoracic transplantation. A historical
      series of 25 patients who received OKT3 (5 mg/day for 10 days) was compared with
      our current experience with 14 patients treated with tacrolimus (0.1 mg/kg/day
      targeting whole blood concentrations of 13 to 18 ng/ml): all 39 patients having
      persistent rejection unresponsive to treatment at the time of conversion. Mean
      periods of follow-up were 842.9 days and 342.6 days, respectively. Actuarial 1
      year patient survival rates were 64.0% and 76.2% for the OKT3 and tacrolimus
      treatment groups, with most of the deaths in the OKT3 group occurring early (p =
      0.064). Causes of death for patients receiving OKT3 included acute rejection (n =
      5), infection (n = 3), carcinoma (n = 2), multiorgan failure (n = 1) and graft
      vessel disease (n = 1). The two deaths in the tacrolimus treatment group were the
      result of infections. Eighty percent of patients treated with OKT3 subsequently
      experienced further rejection episodes, in many cases necessitating methotrexate
      therapy. In contrast, only one patient (7.1%) from the tacrolimus group was
      diagnosed with rejection after conversion (p < 0.001). In conclusion, when
      compared with OKT3 therapy, a switch in baseline immunosuppression from
      cyclosporine to tacrolimus seems to be markedly more effective, as well as being
      safe for the treatment of persistent acute rejection.

PMID- 9286772
TI  - The incremental risk of female sex in heart transplantation: a multiinstitutional
      study of peripartum cardiomyopathy and pregnancy. Cardiac Transplant Research
      Database Group.
AB  - BACKGROUND: Controversy remains regarding the reason females seem to be at
      increased risk for rejection after heart transplantation. Therefore this study
      was performed to define the effect of a pretransplantation diagnosis of
      peripartum cardiomyopathy and the effect of previous pregnancy on the outcome
      (incidence of rejection and death) of females after heart transplantation.
      METHODS: In this multiinstitutional study of 3244 adult (greater than 13 years of
      age) heart transplant recipients, (a) the outcome of 40 females who underwent
      transplantation for peripartum cardiomyopathy was compared with that of 200
      females of childbearing age (13 to 45 years) who underwent transplantation for
      other indications and (b) the posttransplantation outcome of 543 females with a
      history of pregnancy was compared with that of 101 nulliparous adult females and
      2562 adult males. RESULTS: The posttransplantation outcome of females with a
      history of peripartum cardiomyopathy was similar to that of females of
      childbearing age who underwent transplantation for other indications. However,
      parous females had a significantly shorter time to first rejection (p < 0.0001)
      and greater cumulative rejection than nulliparous females or males. By
      multivariable analysis, the risk factors for cumulative rejection at 1 year were
      a history of pregnancy (p < 0.0001), younger recipient age (p < 0.0001),
      induction therapy (p < 0.0001), and the number of human leukocyte antigen-DR
      mismatches (p = 0.007). CONCLUSION: Our data suggest that it is previous
      pregnancy, and not sex per se, that is associated with an increased frequency of
      rejection in females after heart transplantation.

PMID- 9286773
TI  - Heart transplant rejection with hemodynamic compromise: a multiinstitutional
      study of the role of endomyocardial cellular infiltrate. Cardiac Transplant
      Research Database.
AB  - BACKGROUND: The natural history of patients experiencing hemodynamic compromise
      with rejection has been incompletely characterized. This multiinstitutional study
      examined the outcome of such episodes, particularly with regard to the extent of
      cellular infiltrate on the index endomyocardial biopsy. METHODS: From January 1,
      1990, through June 30, 1994, 3367 patients in the Cardiac Transplant Research
      Database experienced 4137 episodes of rejection. Severe hemodynamic compromise
      occurred in approximately 5% of the rejection episodes, and this proportion
      remained relatively constant over time. RESULTS: Recipient risk factors for
      rejection with severe hemodynamic compromise included black race, female
      recipient sex, and diabetes. The 3-month actuarial survival rate was 60% after
      rejection with severe hemodynamic compromise versus 95% after rejection with no
      or mild compromise. Low initial biopsy score conferred a higher early survival,
      but a lower survival at 2 years after rejection with severe hemodynamic
      compromise. Among patients who survive an initial rejection episode with severe
      hemodynamic compromise, survival at 2 years after an episode was 46% among those
      who had a low initial biopsy score versus 84% with a high biopsy score.
      CONCLUSIONS: Rejection with hemodynamic compromise, although rare, represents a
      major complication of heart transplantation with a poor long-term outcome.
      Survivors of hemodynamically compromising rejection episodes associated with low
      biopsy scores in the International Society for Heart and Lung Transplantation
      grading system have a significantly worse long-term outcome than survivors of
      episodes associated with high scores. These findings suggest that immunologic
      mechanisms other than lymphocytic infiltration of the cardiac allograft are
      important and distinct causes of allograft dysfunction.

PMID- 9286774
TI  - The influence of infection on survival and successful transplantation in patients
      with left ventricular assist devices.
AB  - BACKGROUND: Mechanical cardiac assistance has recently emerged as a tenable
      option in the treatment of end-stage heart failure. In spite of recent technical
      improvements that have reduced the incidence of life-threatening complications,
      the reported frequency of infections in these patients has remained high.
      METHODS: Over a 5-year period, 60 patients underwent insertion of a left
      ventricular assist device (LVAD) at our institution. Detailed medical records
      were kept prospectively for all patients, and a variety of endpoints were
      analyzed, including the incidence, nature, and sequelae of infections before and
      after LVAD implantation and after transplantation. RESULTS: Twenty-nine of 60
      patients (48%) undergoing LVAD insertion subsequently had development of
      infections. The most frequent sites of infection were blood, LVAD drivelines, and
      central venous catheters, representing 61% of all infections. At the time of LVAD
      implantation, 13 of 60 patients (22%) had culture-proven infections. In spite of
      an increased incidence of subsequent infection (77% vs 40%), there were no
      differences in rates of mortality (31% vs 26%), LVAD endocarditis, (23% vs 11%)
      and eventual transplantation (62% vs 57%) between these patients and those
      without periimplantation infections. Although the overall mortality rate was not
      influenced by infections during LVAD support (28% vs 26%), the development of
      LVAD endocarditis was associated with a high mortality rate. Finally, although
      patients with infections during LVAD support had significantly longer median
      support times than those who remained infection free (101 vs 49 days,
      respectively), there was no difference in the rate of successful transplantation
      (59% vs 58%) or in the rate of infection after transplantation (35% vs 28%).
      CONCLUSIONS: Infections are common in patients undergoing LVAD support, but they
      do not adversely affect survival, the rate of successful transplantation, or the
      incidence of posttransplantation infection. Periimplantation infections may
      increase the risk of subsequent infections, but they also do not influence
      survival or transplantability. Patients with development of LVAD endocarditis are
      at increased risk for morbidity and death and require early and aggressive
      therapy, potentially including device explantation.

PMID- 9286775
TI  - "Refractoriness" of airflow obstruction associated with isolated lymphocytic
      bronchiolitis/bronchitis in pulmonary allografts.
AB  - The clinical significance of an isolated "lymphocytic bronchiolitis/bronchitis"
      (grade B) as detected in transbronchoscopic biopsy specimens (TBB) is unclear. We
      therefore have reviewed the spirometric responses associated with isolated grade
      B diagnoses and contrasted them with episodes of "acute cellular rejection"
      (grade A); the latter are manifested by "perivascular lymphocytic infiltration."
      Because lymphocytic bronchiolitis/ bronchitis is considered a nonspecific
      histologic pattern that may be observed with either allograft rejection or
      respiratory infections, episodes were analyzed with respect to the presence
      (grade B [+] CMV) or absence (grade B [-] CMV) of cytomegalovirus infection. The
      maximum forced expiratory volume in 1 second (FEV1) during the preceding 3 months
      was used as a baseline for computing percent change in FEV1 coincident with
      transbronchoscopic biopsies (delta %FEV1 PRE) and maximum values obtained during
      the 3 months subsequent to specific therapies (delta %FEV1 POST). All episodes of
      acute cellular rejection (grades A1 to 4) and symptomatic lymphocytic
      bronchiolitis/bronchitis (grade B) were treated with "pulsed-dose"
      methylprednisolone, whereas intravenous ganciclovir was administered to patients
      at risk for recrudescence of cytomegalovirus. Between March 1, 1989, and
      September 1, 1995, 366 TBB procedures were performed for clinical indications in
      57 lung transplant recipients. Histologic diagnoses with acceptable serial
      spirometric values included grade A1 (n = 9), grade A2 (n = 27), grade A3 (n =
      2), grade B(-)CMV (n = 25) and grade B(+)CMV (n = 9). The delta %FEV1 PRE
      coincident with TBB were not statistically different for the different histologic
      groups. For grade A1, delta %FEV1 PRE was -14.6% +/- 5.2% (X +/- SEM); A2, -7.6%
      +/- 1.8%; B(-)CMV, -14.8% +/- 3.9%; and B(+)CMV, -14.8% +/- 2.3%. After
      treatment, the delta %FEV1 POST, relative to baseline values, were for grade A1, 
      8.8% +/- 7.1%, A2, +0.26% +/- 2.6%; B(-)CMV, -12.0% +/- 3.8%; and B(+)CMV, -6.2%
      +/- 2.8%. The delta %FEV1 POST values after pulsed methylprednisolone were
      significantly greater for histologic grade A2 than grade B(-)CMV (unpaired
      Student's t test, P < 0.01; 95% confidence interval for the difference of means:
      3.34% to 21.2%). Grade A2 rejection was associated with spirometric improvement
      to within 10% of baseline values in 52% of episodes; whereas with grade B(-)CMV,
      this salutary response was observed in only 32% of episodes. Bronchiolitis
      obliterans syndrome stage 1b developed in 13 of 20 (65%) recipients,
      approximately 7.9 +/- 3.4 months after detection of histologic grade B and 21.2
      +/- 9.5 months after transplantation. We conclude that the relative
      "refractoriness" of histologic grade B most likely reflects a continuum of
      bronchiolitis obliterans after lung transplantation and, hence, may warrant
      different immunosuppressive strategies. Furthermore, spirometric decrement
      associated with acute cellular rejection (grade A) may be ameliorated, but often
      not completely reversed, after pulsed methylprednisolone. We speculate that
      surveillance TBB may prove rewarding by enabling an earlier detection of these
      histologic diagnoses before the development of physiologic impairment.

PMID- 9286776
TI  - The effect of combination therapy with EPC-K1 and low-dose cyclosporine to
      pulmonary allograft after rat lung transplantation.
AB  - BACKGROUND: EPC-K1, a diester of alpha-tocopherol and ascorbic acid, has a
      hydroxyl radical scavenging effect and also has antiinflammatory properties
      through its phospholipase A2 inhibitory effect. With a view to decreasing the
      total dose of cyclosporine, the effect of a combination of EPC-K1 and
      cyclosporine on rejection was investigated by use of a rat orthotopic left lung
      transplantation model. METHODS: Orthotopic left lung transplantation was
      performed with brown Norway rats as donors and Lewis rats as recipients.
      Recipients were assigned to one of four experimental groups. Control group
      animals were given no immunosuppression. The EPC-K1 group received continuous
      intraperitoneal infusion of EPC-K1 (5 mg/kg/day) by osmotic pump on postoperative
      days (POD) 0 through 6. The cyclosporine group received cyclosporine (1.25
      mg/kg/day) intramuscularly on POD 1 through 6. The EPC-K1 + cyclosporine group
      received both EPC-K1 and cyclosporine in the same manner as the EPC-K1 and
      cyclosporine groups. Recipients were killed on POD 7, and the transplanted lungs
      were examined histologically and graded in a blinded fashion (grade 0 to 4). The
      effect of EPC-K1 and cyclosporine treatment on the primary immune response was
      examined by mixed lymphocyte reaction (MLR) between brown Norway rat stimulator
      cells (treated with mitomycin) added to Lewis rat responder lymphocytes. RESULTS:
      Control group animals exhibited the severe destructive changes of grade 4 lung
      rejection. The EPC-K1 + cyclosporine group showed significantly less graft
      rejection compared with the EPC-K1 group and the cyclosporine group (p < 0.01).
      In MLR assay, the EPC-K1 + cyclosporine group (793 +/- 210 cpm) showed
      significantly suppressed lymphocyte proliferation compared with the control group
      (2188 +/- 360 cpm), EPC-K1 group (1869 +/- 541 cpm), and cyclosporine group (1873
      +/- 326 cpm) (p < 0.01). CONCLUSION: EPC-K1 significantly improves effects of
      cyclosporine at lower doses both in preventing pulmonary allograft rejection and
      in suppressing lymphocyte proliferation in MLR.

PMID- 9286778
TI  - Study of muscular and ventricular function in dynamic cardiomyoplasty: a ten-year
      follow-up.
AB  - BACKGROUND: The basic physiologic principle underlying cardiomyoplasty is long
      term electrostimulation of a latissimus dorsi muscle (LDM) wrapped around the
      heart to obtain a phasic activity that could be integrated with ventricular
      kinetics. The aim of cardiomyoplasty is to prolong survival and to improve the
      quality of life of patients with severe chronic and irreversible myocardial
      failure by improving systolic contraction and correcting diastolic dysfunction.
      METHODS: To evaluate the long-term outcome of cardiomyoplasty, we investigated 82
      patients electively undergoing this procedure in-our hospital. All patients had
      severe chronic heart failure that did not respond to optimal medical treatment.
      Patients had a mean age of 50 +/- 12 years (84% males). The cause of heart
      failure was ischemic (55%), idiopathic cardiomyopathy (34%), ventricular tumor
      (6%), and other (5%). The mean follow-up was 4.3 years. RESULTS: The mean New
      York Heart Association functional class improved after operation from 3.2 to 1.8.
      Average radioisotopic left ventricular ejection fraction increased from 17% +/-
      6% to 28% +/- 3% (p < 0.05). Stroke volume index increased from 35 +/- 9 to 46 +/
      8 ml/beat/m2 (p < 0.05). The heart size remained stable at long term (evaluated
      by echo and computed tomography scanning). After cardiomyoplasty the number of
      successive hospitalizations resulting from congestive heart failure was reduced
      to 0.4 hospitalizations/patient/year (before operation 2.5, p < 0.05). Computed
      tomography scans showed at long-term a preserved LDM structure in 82% of patients
      who underwent operation. Survival probability at 7 years was 54% for the totality
      of patients, and 66% for patients who underwent operation in New York Heart
      Association functional class 3. Five patients underwent heart transplantation
      after cardiomyoplasty (mean delay 29 months), principally as a result of the
      natural evolution of their underlying heart disease, without major technical
      difficulties. CONCLUSIONS: Our 10-year clinical experience demonstrates that
      cardiomyoplasty increases ejection fraction, improves functional class, and
      ameliorates quality of life. Ventricular volumes and diameters remain stable long
      term. LDM structure is maintained long term if electrostimulation is performed
      avoiding excessive myostimulation. Patient selection is the most important
      determinant for early and late outcome. Late death in patients undergoing
      cardiomyoplasty is principally due to sudden death. Our future aim is to
      incorporate a cardioverter-defibrillator in the cardiomyostimulator, thus
      improving long-term results. Cardiomyoplasty may delay or prevent end-stage heart
      failure and the need for heart transplantation.

PMID- 9286777
TI  - Treatment of subclinical fluid retention in patients with symptomatic heart
      failure: effect on exercise performance.
AB  - BACKGROUND: Patients with heart failure frequently have elevated intracardiac
      diastolic pressures but no clinical evidence of excess fluid retention. We
      speculated that such pressure elevations may indicate subclinical fluid retention
      and that removal of this fluid could improve exercise intolerance. METHODS: To
      test this hypothesis, we studied 10 patients with right atrial pressure > or = 8
      mm Hg but without rales, edema, or apparent jugular venous distension. Right
      sided heart catheterization was performed, after which patients underwent maximal
      treadmill cardiopulmonary testing. Patients were then hospitalized and underwent
      maximal diuresis, after which exercise was repeated. RESULTS: Before diuresis,
      right atrial pressure averaged 16 +/- 5 mm Hg (+/-standard deviation), pulmonary
      capillary wedge pressure 30 +/- 6 mm Hg, and peak exercise Vo2 11.2 +/- 2.3
      ml/min/ kg. Patients underwent diuresis of 4.5 +/- 2.2 kg over 4 +/- 2 days to a
      resting right atrial pressure of 6 +/- 4 and wedge pressure of 19 +/- 7 mm Hg.
      After diuresis, all patients reported overall symptomatic improvement. Maximal
      exercise duration increased significantly from 9.2 +/- 4.2 to 12.5 +/- 4.7
      minutes. At matched peak workloads, significant improvements were also seen in
      minute ventilation (45 +/- 12 to 35 +/- 9 L/min), lactate levels (42 +/- 16 to 29
      +/- 9 mg/dl), and Borg dyspnea scores (15 +/- 3 to 12 +/- 4) (all p < 0.05).
      CONCLUSIONS: Invasive hemodynamic monitoring allows the identification of excess
      fluid retention in patients with heart failure when there are no clinical signs
      of fluid overload. Removal of this subclinical excess fluid improves exercise
      performance and exertional dyspnea.

PMID- 9286779
TI  - Sex and left ventricular volume predict survival in heart transplant candidates
      with peak oxygen uptake between ten and fourteen milliliters per kilogram per
      minute.
AB  - BACKGROUND: The purpose of this study was to identify predictors of survival in
      patients referred for heart transplantation evaluation who had a peak oxygen
      uptake of 10 to 14 ml/kg/min measured during initial cardiopulmonary exercise
      testing. METHODS: Seventy-two patients were identified retrospectively from a
      database of 304 patients who underwent heart transplantation evaluations at our
      center from 1985 to 1995. All 72 patients underwent right-sided heart
      catheterization and first-pass right and left ventricular radionuclide
      ventriculography during cardiopulmonary exercise testing. RESULTS: There were 14
      women and 58 men in the study (mean age 52 +/- 9 years, 80% male, 79% New York
      Heart Association class III/IV, left ventricular ejection fraction of 0.24 +/-
      0.9, and left ventricular end-diastolic volume index of 144 +/- 59 ml). During a
      mean follow-up of 19 +/- 23 months, two women and 32 men (47%) reached the
      combined end point of death (n = 20) or pretransplantation admission for
      inotropic or mechanical support (n = 14). For the entire cohort, analysis of
      clinical, ventriculographic, and exercise parameters identified female sex,
      younger age, and age/ sex-adjusted peak oxygen uptake as independent predictors
      of survival. In men only, age, left ventricular end-diastolic volume index, and
      age/sex adjusted peak oxygen uptake were independent predictors of survival.
      CONCLUSIONS: Among patients referred for heart transplantation evaluation with a
      peak oxygen uptake between 10 to 14 ml/kg/min, younger age, female sex, and
      higher age/ sex-adjusted peak oxygen uptake predict longer survival to the
      combined end point of death or pretransplantation admission for inotropic or
      mechanical support. These measures may be useful in additional risk
      stratification of such patients.

PMID- 9286781
TI  - Dynamic aortomyoplasty: clinical experience.
AB  - Dynamic aortomyoplasty has been the subject of experimentation for the treatment
      of congestive heart failure during the last few years. This method consists of
      diastolic counterpulsation of the ascending aorta through the stimulation of the
      latissimus dorsi wrapped around it. This report describes the results of
      aortomyoplasty in a patient with dilated cardiomyopathy resulting from Chagas'
      disease and contraindications for heart transplantation or cardiomyoplasty.

PMID- 9286782
TI  - Laser in situ keratomileusis for myopia of -1 to -3.50 diopters.
AB  - BACKGROUND: Laser in situ keratomileusis (LASIK) is the procedure of choice for
      high myopia. We present a study of 85 eyes undergoing LASIK for myopia between 
      1.00 and -3.50 diopters (D) and assess the safety and efficacy of the procedure
      for treatment of low myopia. METHODS: Eighty-five eyes of 47 patients with a mean
      age of 29 years, (range, 18 to 56 yrs) underwent LASIK using the Chiron
      microkeratome and the Nidek EC-5000 excimer laser. Mean preoperative myopia was 
      2.09 D and mean astigmatism was 0.86 D. All other ocular pathology was ruled out
      before surgery. Mean follow-up was 48 days (range, 1 day to 13 mo). RESULTS:
      Uncorrected visual acuity of 6/9 or better at 1 week was achieved in 44 eyes
      (52%); at 1 month in 68 eyes (80%); and at 6 months in 70 eyes (93%). Pain score
      was minimal with the majority of patients having no postoperative pain. One eye
      suffered a serious postoperative complication of corneal abscess which resolved
      with treatment, but left a corneal scar and visual acuity of 6/60. CONCLUSION:
      LASIK is a safe and effective procedure for low amounts of myopia; it also
      provides early visual rehabilitation and markedly reduced pain and discomfort to
      patients undergoing refractive surgery.

PMID- 9286780
TI  - Prostaglandin E1 infusion compared with prostacyclin infusion in patients with
      refractory heart failure: effects on hemodynamics and neurohumoral variables.
AB  - Prostaglandin E1 or prostacyclin were randomly infused in 18 patients with severe
      chronic heart failure who did not respond to oral treatment. Maximally tolerated
      dosages of both agents increased cardiac index; however, only prostacyclin
      decreased mean arterial pressure and increased plasma norepinephrine
      significantly. Twelve hours after 50% peak dose reduction, atrial natriuretic
      peptide levels, right atrial pressure, mean pulmonary artery pressure, and mean
      arterial pressure continued to decrease with prostaglandin E1, whereas the
      increase in cardiac index was sustained; in contrast, at 50% prostacyclin dose
      reduction, cardiac index decreased toward baseline, suggesting that, with reduced
      dosages for chronic infusions, desired hemodynamic changes seem to be sustained
      with prostaglandin E1 only.

PMID- 9286783
TI  - Laser in situ keratomileusis for myopia of -2 to -25 diopters.
AB  - PURPOSE: To evaluate excimer laser in situ keratomileusis in the treatment of
      low, high, and excessively myopic eyes in Taiwan, 77 patients (104 eyes) were
      treated with Nidek EC-5000 excimer laser and divided into four groups. METHODS:
      In situ keratomileusis was performed with a Chiron or SCMD microkeratome. The
      Nidek EC-5000 excimer laser was used, with multiple passes and a multiple zone
      ablation technique was performed for myopia higher than -10.00 D. RESULTS: In
      eyes with a preoperative spherical power equal to or less than -7.00 D (29 eyes
      of 18 patients), the preoperative cycloplegic mean spherical equivalent
      refraction was -5.44 +/- 1.36 D. The mean postoperative subjective spherical
      equivalent refraction was 0.25 +/- 0.64 D at 1 month, 0.056 +/- 0.55 D at 3
      months, -0.069 +/- 0.415 D at 6 months, and 0.022 +/- 0.496 D at 9 months. The
      predictability of postoperative 9 month results demonstrated that 86.21% of eyes
      were within +/-0.50 D, 96.55% were within +/-1.00 D, and 100% were within +/-2.00
      D of emmetropia. In eyes with a preoperative spherical power equal to or less
      than -10.00 D and higher than -7.00 D, 26 eyes of 17 patients had a preoperative
      cycloplegic mean spherical equivalent refraction of -8.41 +/- 0.84 D. The mean
      postoperative subjective spherical equivalent refraction was -0.043 +/- 1.15 D at
      1 month, -0.12 +/- 0.92 D at 3 months, -0.21 +/- 1.05 D at 6 months, and -0.37 +/
      1.04 D at 9 months. The predictability of postoperative 9 month results
      demonstrated that 76.92% of eyes were within +/-0.50 D, 80.77% were within +/
      1.00 D, and 96.5% were within +/-2.00 D of emmetropia. In eyes with a
      preoperative spherical power equal to or less than -15.00 D and more than than 
      10.00 D, 40 eyes of 27 patients had a preoperative cycloplegic mean spherical
      equivalent refraction of -12.65 +/- 1.51 D. The mean postoperative subjective
      spherical equivalent refraction was 0.275 +/- 1.72 D at 1 month, -0.30 +/- 1.34 D
      at 3 months, -0.47 +/- 1.23 D at 6 months, and -0.62 +/- 1.23 D at 9 months. The
      predictability of postoperative 9 month results demonstrated that 62.5% of eyes
      were within +/-0.50 D, 75% were within +/-1.00 D, and 87.5% were within +/-2.00 D
      of emmetropia. For 19 eyes of 15 patients with a preoperative spherical power
      greater than -15.00 D, the preoperative cycloplegic mean spherical equivalent
      refraction was -19.53 +/- 2.61 D. The mean postoperative subjective spherical
      equivalent refraction was -0.40 +/- 1.22 D at 1 month, -0.69 +/- 1.34 D at 3
      months, -0.83 +/- 1.40 D at 6 months, and -0.65 +/- 2.99 D at 9 months. The
      predictability of postoperative 9 month results demonstrated that 31.5% of eyes
      were within +/-0.50 D, 52.63% were within +/-1.00 D, and 63.16% were within +/
      2.00 D. CONCLUSION: LASIK is a safe and effective technique for the treatment of
      low, high, and excessive myopia.

PMID- 9286784
TI  - Use of bandage contact lenses after laser in situ keratomileusis.

PMID- 9286785
TI  - Laser in situ keratomileusis for hyperopia.
AB  - PURPOSE: To study the efficacy of laser in situ keratomileusis (LASIK) for
      hyperopia. METHODS: We performed LASIK on 21 eyes using the Nidek EC-5000 excimer
      laser with software version 2.18 AH. The Chiron Automated Corneal Shaper was used
      to create the flap. Retreatments were needed in seven eyes due to decentration or
      undercorrection. RESULTS: Although a high rate of satisfaction was noted among
      patients, complications were encountered such as decentration (three eyes),
      undercorrection (four eyes); one patient progressed to low myopia with a loss of
      spectacle-corrected visual acuity and one patient had regression 3 months after
      the initial LASIK. CONCLUSION: Although this technique has several advantages
      over other techniques (holmium, ALK, PRK, hexagonal RK), it has a high rate of
      retreatment and some complications. Software refinement is needed, and patients
      should be adequately informed about what to expect from this technique.

PMID- 9286786
TI  - Laser in situ keratomileusis for hyperopia: new software.

PMID- 9286787
TI  - First year experience with laser in situ keratomileusis.

PMID- 9286788
TI  - Patient satisfaction after photorefractive keratectomy for low myopia using the
      visual analogue scale.
AB  - OBJECTIVE: To subjectively assess patient satisfaction after photorefractive
      keratectomy (PRK) for low myopia using the visual analogue scale. METHODS: We
      evaluated the satisfaction of 28 patients (53 eyes) who underwent PRK. Their
      baseline myopia ranged from -0.50 to -5.00 diopters (D) with a refractive
      cylinder ranging between plano to -2.00 D. They were all treated using the Nidek
      EC-5000 scanning excimer laser with an ablation zone diameter of 5.5 mm and a
      transition zone diameter of 7.0 mm. Mean follow-up time was 11 months. RESULTS:
      Mean satisfaction in this group of patients was 90.95 +/- 8.9%. We found that
      age, baseline astigmatism, postoperative refraction, and postoperative haze
      influenced the satisfaction outcome. CONCLUSION: Satisfaction assessment after
      PRK in patients with low myopia using the visual analogue scale is simple,
      subjective, reproducible, quick, and probably reliable.

PMID- 9286789
TI  - Photorefractive keratectomy in 621 myopic eyes.

PMID- 9286790
TI  - Regression of myopia induced by pregnancy after photorefractive keratectomy.
AB  - BACKGROUND: We evaluated refractive corneal changes that occurred in women who
      become pregnant after undergoing excimer laser photorefractive keratectomy (PRK)
      for the treatment of myopia. METHODS: Refractive results of 18 eyes of nine women
      who underwent PRK and became pregnant during the follow-up period were reviewed.
      All eyes were followed for a least 12 months after PRK. Subjective refraction,
      slit-lamp microscopy, and intraocular pressure were measured at each follow-up
      examination. RESULTS: Twelve of 18 eyes (66%) had myopic regression during the
      follow-up period. The regression was associated with 1+ to 2+ corneal haze in 10
      of these 12 eyes (83.3%). The three women (6 eyes) who had stable refractions
      after PRK became pregnant at least 5 months postoperatively. The corneal haze and
      the associated myopic regression improved in 50% of the eyes after delivery.
      CONCLUSION: Pregnancy seems to induce effects on corneal wound healing following
      PRK.

PMID- 9286791
TI  - Seasonal variations in refractive results following excimer laser photorefractive
      keratectomy.
AB  - PURPOSE: To evaluate the effect of seasonal factors on the final refractive
      outcome following excimer laser photorefractive keratectomy (PRK). METHODS: We
      examined the final refractive outcome for 5367 patients who had undergone PRK and
      photoastigmatic refractive keratectomy (PARK) over an 18-month period, April 1994
      to August 1995, with a Nidek EC-5000 excimer laser and analyzed them by monthly
      and seasonal groups at time of treatment. RESULTS: We were unable to demonstrate
      any significant difference in patients grouped according to season at time of
      treatment. CONCLUSION: We would not recommend any seasonal-related adjustment for
      treatment with the Nidek EC-5000 excimer laser.

PMID- 9286792
TI  - Double clear zone photorefractive keratectomy to correct compound myopic
      astigmatism.

PMID- 9286793
TI  - Epithelial cell adhesion and haze after photorefractive keratectomy.

PMID- 9286794
TI  - Photorefractive keratectomy for myopia and photoastigmatic keratectomy for
      astigmatism.
AB  - BACKGROUND: We conducted a clinical trial to evaluate the efficacy and safety of
      excimer laser photorefractive keratectomy (PRK) and photoastigmatic refractive
      keratectomy (PARK) using the Nidek EC-5000 excimer laser. METHODS: A total of 67
      eyes from 47 patients whose average age was 35 years were enrolled in the study.
      The mean spherical equivalent of the manifest refraction before surgery was -7.50
      diopters (D). Patients were followed for at least 6 months. One year after
      surgery, uncorrected visual acuity improved in 98% of the eyes, while spectacle
      corrected visual acuity had not deteriorated in any patient. The achieved
      corrections were within +/-1.00 D of attempted correction in 72.5% of eyes.
      Predictability was poor in eyes in which the correction was more than 10.00 D.
      Subepithelial haze occurred in all eyes to minimal extent, and disappeared
      gradually. CONCLUSION: Photorefractive keratectomy and photoastigmatic refractive
      keratectomy, performed with the Nidek EC-5000 excimer laser, is a reliable and
      adequately safe procedure to correct myopia of a limited range.

PMID- 9286795
TI  - Effects of topical corticosteroids after photorefractive keratectomy.
AB  - PURPOSE: To assess the effects of topical corticosteroids (fluoromethalone)
      following photorefractive keratectomy (PRK). METHODS: Both eyes of 654 patients
      had PRK with a minimum of 4 months between treatments. Topical corticosteroids
      were prescribed for one eye only. Endpoints were assessed by comparing the ratio
      of intended to actual refractive change in the corticosteroid treated eye with
      the fellow eye (no corticosteroid use). RESULTS: The corticosteroid treated eyes
      showed a mean percentage correction of 95.7% compared to the untreated fellow
      eyes, which achieved a percentage correction of 103.3%-statistical significance
      of p = 0.00001. There was more of a trend toward regression in the corticosteroid
      treated eyes despite intervention with fluoromethalone. CONCLUSION: Topical
      corticosteroids showed very little positive effect on regression of effect after
      PRK.

PMID- 9286796
TI  - Photorefractive keratectomy for hyperopia after radial keratotomy.
AB  - BACKGROUND: Progressive hyperopia is a common complication following radial
      keratotomy. METHODS: Ten eyes of ten consecutive patients with hyperopia after
      radial keratotomy between +1.75 and +4.00 diopters (D) were treated with the
      hyperopia module of the Nidek Model EC-5000 excimer laser. The mean preoperative
      uncorrected visual acuity was 0.38 (20/60+). RESULTS: After excimer laser
      photorefractive keratectomy (PRK), mean uncorrected visual acuity improved to .72
      (20/30+). No complications occurred with the exception of one eye with haze
      greater than 2+. CONCLUSION: PRK for hyperopia is a valuable method for
      correcting hyperopia after radial keratotomy.

PMID- 9286798
TI  - Patient satisfaction after photorefractive keratectomy.

PMID- 9286797
TI  - Effect of topical tranilast and corticosteroids on subepithelial haze after
      photorefractive keratectomy in rabbits.
AB  - BACKGROUND: Tranilast (trade name Rizaben), an anti-allergic drug with anti
      inflammatory effects, is thought to inhibit synthesis of extracellular matrix of
      fibroblasts through the suppression of TGF-beta. We evaluated the effect of
      topical tranilast on the subepithelial haze that developed after excimer laser
      keratectomy and its effect was compared with that of betamethasone eye drops
      METHODS: Excimer laser keratectomy (phototherapeutic keratectomy mode) was
      performed with the Nidek EC-5000 excimer laser on 16 rabbit corneas (eight
      rabbits). From the second postoperative day, topical 2% tranilast was instilled
      in the right eye and the control solution in the left eye, four times daily.
      Until the fourth week after the operation, we measured the densitometric values
      of scattered light intensity of the subepithelial haze with an anterior ocular
      analyzer, EAS-1000 (Nidek). At the fifth postoperative week, light and electron
      microscopy and immunohistochemistry with an antibody to TGF-beta were also
      performed. RESULTS: Densitometric values of the subepithelial haze in the corneas
      treated with 2% tranilast were slightly less than those of the subepithelial haze
      in the control corneas. However, the values of the subepithelial haze in the
      betamethasone-treated corneas were significantly less than those in control
      corneas. Histochemical examinations revealed that topical tranilast had a small
      effect on the subepithelial haze after excimer laser keratectomy in rabbits.
      CONCLUSION: Topical 0.1% betamethasone can limit the amount of subepithelial haze
      and tranilast may inhibit development of subepithelial haze by the suppression of
      TGF-beta.

PMID- 9286799
TI  - Predictable and unpredictable parameters of photorefractive keratectomy.

PMID- 9286800
TI  - Pulsatile ocular blood flow variations with axial length and refractive error.
AB  - Ocular pulse amplitude (PA) and pulsatile ocular blood flow (POBF) were studied
      in 80 eyes from 80 subjects with a refractive error between +3.00 and -28.00 dpt
      using the Langham Ocular Blood Flow System. PA and POBF were correlated with
      axial length and refractive error using linear regression analysis. A significant
      correlation (p < 0.001) was found between PA and axial length (r = -0.787), PA
      and refractive error (r = 0.775), POBF and axial length (r = -0.655) and POBF and
      refractive error (r = 0.650). Myopic eyes were further divided into subgroups
      according to axial length, refractive error and fundus oculi characteristics.
      Each subgroup exhibited a significant reduction in PA (p < 0.001) compared to the
      control group. POBF reduction was significant in every subgroup except the
      subgroup with a refractive error lower than 6 dpt and the subgroup with an axial
      length shorter than 26 mm.

PMID- 9286801
TI  - Noncontact holmium:YAG laser thermal keratoplasty to correct hyperopia: 18-month
      follow-up.
AB  - PURPOSE: To assess the safety and efficacy of noncontact holmium:yttrium
      aluminium garnet laser thermal keratoplasty (Ho:YAG LTK) for correction of low to
      moderate hyperopia. METHODS: We performed noncontact Ho:YAG LTK on 1 eye each of
      28 patients for correction of hyperopia up to +3.88 dpt. Treatments were
      conducted with 1 or 2 symmetrical octagonal rings of 8 spots/ring with centerline
      diameters of 6 mm (1 ring) or 6 and 7 mm (2 rings), 10 pulses of laser light at 5
      Hz pulse repetition frequency, variable pulse energy in the range of 208-242 mJ
      and a nominal spot diameter between 615 and 623 microns. RESULTS: At 18 months
      after surgery, 20 of 22 (91%) treated patient eyes had improved uncorrected
      distance visual acuity. The mean change in subjective manifest refraction
      (spherical equivalent) was -0.52 +/- 0.35 dpt and -1.41 +/- 0.53 dpt for 1- and 2
      ring treatment groups, respectively, with good stability in the refractive change
      after 6 months. The mean induced refractive astigmatism was small (0.30 +/- 0.37
      dpt/0.25 +/- 0.29 dpt for 1-/2-ring treatments). None of the eyes lost 2 or more
      lines of spectacle-corrected distance visual acuity. There were no clinically
      significant changes in glare and contrast sensitivity. CONCLUSIONS: Noncontact
      LTK treatment of low hyperopia is safe and effective, and it is more stable and
      less prone to induce astigmatism than previously reported contact mode LTK
      treatments.

PMID- 9286802
TI  - Subretinal microsurgery with gradient index endoscopes.
AB  - State-of-the-art subretinal surgery involves a standard three-port pars plana
      entry, followed by an iatrogenic retinotomy to access the subretinal space.
      Subretinal manipulations through a small retinotomy are made possible by
      specially designed instruments. As the surgeon looks through the vitreous cavity,
      all subretinal maneuvers are obscured by the overlying retina. Consequently, the
      surgeon is operating 'blindly' and has to rely on 'feeling' rather than direct
      visualization. Micro-endoscopic viewing systems are the ideal solution for
      visualization during subretinal surgery. Until now, such endoscopes were either
      too large for intraocular use or lacked sufficient resolution, especially at a
      short working distance. Recently, a gradient index (GRIN) endoscope was developed
      (Insight Instruments, Inc., Lake Mary, Fla., USA) combining a small diameter
      (0.89 mm, 20 gauge) and incorporating excellent optical resolution, even at
      extremely close working distances. After ballooning a limited part of the retina
      without creating a retinal hole, the 20-gauge GRIN endoscope can be introduced
      into the subretinal space through the sclera and choroid, posterior to the pars
      plana. Surgical instruments can then be introduced into the subretinal space
      through a second neighboring sclerotomy. Thus, subretinal surgery can be
      performed under direct endoscopic control. As a result of direct visualization,
      the surgeon may perform certain surgical procedures with greater accuracy, i.e.,
      subretinal neovascular membranes may be dissected meticulously from the
      neurosensory retina and retinal pigment epithelium, minimizing damage to both
      structures. The feeding choroidal vessel can be identified and directly
      coagulated, which is usually very difficult during conventional subretinal
      surgery. Endoscopic subretinal surgery is thus a significant improvement over
      conventional methods, avoiding the need for a retinotomy and increasing the
      safety and facility of the surgery itself.

PMID- 9286803
TI  - Incidence of retinal vein occlusion at the Glaucoma Clinic of Hiroshima
      University.
AB  - We prospectively surveyed the incidence of retinal vein occlusion (RVO) at the
      glaucoma clinic of Hiroshima University between 1986 and 1991. Among 433 glaucoma
      patients, 18 (4.2%) subsequently presented with RVO, 9 had central retinal vein
      occlusion (CRVO) and 9 exhibited branch retinal vein occlusion (BRVO). Seven of
      87 (8.1%) patients with primary angle closure glaucoma exhibited RVO, showing the
      highest incidence among glaucoma types. The incidence of RVO detected by the
      general outpatient clinic was 0.59% during the same period. The BRVO/CRVO ratio
      in the glaucoma clinic was 1.0, while it was 4.3 in the general outpatient
      clinic. Glaucoma is an important risk factor for the development of RVO,
      especially CRVO.

PMID- 9286804
TI  - Prophylactic intravenous ondansetron in patients undergoing cataract extraction
      under general anesthesia.
AB  - During the past decade the demand for outpatient surgery has grown rapidly.
      Postoperative nausea and vomiting is one of the more common undesirable
      consequences of surgery, which may significantly delay the patient's discharge
      from the ambulatory surgery center. None of the currently used antiemetic drugs
      is considered totally effective in abolishing nausea or vomiting. The purpose of
      this study was to compare the efficacy of ondansetron, a highly selective 5
      hydroxytryptamine subtype-3 receptor antagonist, with that of metoclopramide for
      the prevention of postoperative emesis in patients undergoing cataract surgery.
      The incidence of postoperative nausea was significantly less in the ondansetron
      group than that in the metoclopramide group (p = 0.046). Although the incidence
      of vomiting was clinically less frequent in the ondansetron group, there were no
      significant differences between both treatment groups. To our knowledge, this is
      the first study to demonstrate that ondansetron is effective to prevent
      postoperative emesis after extracapsular cataract extraction.

PMID- 9286806
TI  - Angiotensinogen mRNA is synthesized locally in rat ocular tissues.
AB  - Angiotensinogen (ANG) is present in the eye. However, the source has not been
      determined. We showed that ANG mRNA was present in several ocular tissues using
      RT-PCR with ANG-specific primers. One of 10 iris samples (10%), 1 of 10 ciliary
      body samples (10%), 3 of 10 choroid samples (30%) and 9 of 10 retina samples
      (90%) were positive for ANG. Our study provides the first direct evidence that
      the renin-angiotensin system (RAS) component ANG is synthesized locally in the
      eye, especially the retina and choroid portion. These are strategic locations for
      an ocular RAS to influence chorioretinal blood flow, raising the possibility that
      RAS alterations may be involved in chorioretinal vascular disease.

PMID- 9286805
TI  - Histopathological and ultrastructural examination of the rat conjunctiva after
      exposure to tobacco smoke.
AB  - Exposure to tobacco smoke can cause irritation of the conjunctiva. We conducted
      this study to identify the effect of tobacco on rat conjunctiva. Animals were
      divided into experimental and control groups and we exposed the experimental
      group to tobacco smoke. Control group rats inhaled only room air.
      Spectrophotometric analysis of the smoke-air mixture revealed that many toxic
      substances were present in this compound. We found very high levels of plasma
      thiocyanate after exposure to smoke in experimental group animals but no increase
      in the control group. So, this data indicates that these animals inhaled smoke
      effectively in our method. After 3 months conjunctivas were examined by light and
      electron microscopy. In the experimental group, conjunctivas were thinned,
      atrophied and microvillous projections and desmosomal connections were absent in
      comparison with the control conjunctivas. This pathologic change is very similar
      to conjunctival response to chronic irritants of any type.

PMID- 9286807
TI  - Ocular involvement in tuberculoid leprosy--a case report.
AB  - Leprosy is rarely diagnosed in our part of the world. In our 26-year-old patient,
      borderline lepromatous leprosy was first diagnosed in 1992 and was treated with
      Rifoldin, Lemprene and Dapson according to the standard WHO scheme of treatment.
      Ophthalmic examination showed minor epithelial lesions of the cornea in both
      eyes, a reduced corneal reflex in the left eye and a scleral leproma nasally and
      close to the limbus, also in the left eye. In 1995, the patient was examined
      again and was treated as above for lepromata of the left eyebrow nasally and of
      both lower legs. Ophthalmic examination revealed conjunctival irritation,
      anterior uveitis with leprosy pearls on the pupillary margin and secondary
      glaucoma. The glaucoma was treated with hypotonics, the uveitis was treated with
      topical cortisone. The intra-ocular pressure normalised and the uveitis improved.
      Of the two main types of leprosy, lepromatous leprosy and tuberculoid leprosy,
      our patient had the second, milder form.

PMID- 9286808
TI  - Cavernous sinus thrombosis secondary to abdominal wall abscess.
AB  - An 84-year-old Japanese woman had cavernous sinus thrombosis (CST) due to
      abdominal wall abscess. The diagnosis was delayed because abdominal wall abscess
      is an unfamiliar cause of CST, but a definite diagnosis was reached with the use
      of magnetic resonance imaging. We started intravenous antibiotic therapy against
      gram-positive and gram-negative organisms and the patient responded well,
      although the diagnosis was delayed.

PMID- 9286809
TI  - Iris cyst in aphakic patient: improvement of visual acuity after excision.
AB  - Postsurgical or spontaneous iris cyst is a rare finding. Unfortunately, all
      treatments are complicated and the results may be disappointing. We report a case
      of postsurgical iris cyst treated by sector iridectomy with satisfactory recovery
      of visual acuity.

PMID- 9286810
TI  - Concurrent bilateral posterior scleritis and Vogt-Koyanagi-Harada disease in a
      patient with positive rheumatoid factor.
AB  - We examined a 67-year-old man who complained of headache and pain and decreased
      visual acuity in both eyes. The patient had dilated conjunctival and episcleral
      vessels, intracameral cells, shallow anterior chambers, hyperemic swollen optic
      disks, exudative retinal detachment and choroidal detachment. Fluorescein
      angiography showed leakage of dye from the optic disks and choroid into the
      subretinal space. Scleral thickening was found by computed tomography. These
      abnormal findings disappeared within 1 week after treatment with a systemic
      corticosteroid. Laboratory test results showed positive rheumatoid factor. Sunset
      glow fundi and vitiligo developed a few months after the treatment. We believe
      that concurrent bilateral posterior scleritis, Vogt-Koyanagi-Harada disease and
      positive rheumatoid factor, as demonstrated in our patient, may be rare.

PMID- 9286811
TI  - Bilateral horizontal gaze palsy with pontine cavernous hemangioma: a case report.
AB  - A 31-year-old man demonstrating acquired bilateral gaze palsy as an isolated
      symptom of a paramedian pontine reticular formation (PPRF) lesion due to a
      ruptured cryptic cavernous hemangioma is herein reported. MRI revealed a flow
      void surrounded by a hemorrhagic lesion, which was located in the lower dorsal
      part of the pons. This lesion corresponded to the PPRF. His eye movement almost
      completely recovered and MRI revealed the absorption of the hematoma 2 months
      later, with only conservative observation. This is a rare case presenting most
      likely with a minimal lesion for bilateral gaze palsy. Based on the above
      findings it is thus concluded that surgical removal of such a cryptic cavernous
      hemangioma should therefore not be the only choice.

PMID- 9286813
TI  - The effect of nitric oxide synthase blockade and indomethacin on gastric emptying
      and gastric contractility.
AB  - The aim of the present study was to investigate the effect of nitric oxide (NO)
      synthase inhibition on gastric emptying rate in conscious rats and on gastric
      muscle contractility. The involvement of NO was also investigated in indometacin
      induced (25 mg/kg, s.c.) changes in gastric emptying rate and smooth muscle
      contractility. L-NAME (NG-nitro-L-arginine methyl ester; 10 mg/kg, i.v.)
      inhibited the gastric emptying rate compared to controls and this effect was
      abolished by L-arginine (300 mg/kg, i.v.). Similarly, indometacin treatment led
      to a significant delay of gastric emptying rate with respect to vehicle-treated
      rats. Gastric longitudinal and circular muscle strips of L-NAME or indometacin
      treated rats showed a reduction in contractile responses to carbachol. The
      results demonstrate that NO synthase blockade and indometacin treatment delay
      gastric emptying in conscious rats, concomitant with reduced responsiveness to
      carbachol, in vitro.

PMID- 9286812
TI  - Effects of various analgesic and anti-inflammatory drugs on endotoxin-induced
      hyperalgesia in rats and mice.
AB  - A new model of endotoxin (ET)-induced hyperalgesia has been used to test the
      effects of four classes of drugs in rats and mice. Hyperalgesia was assessed by
      paw pressure (PP), hot plate (HP) and tail flick (TF) tests. Each drug was
      injected intraperitoneally 24 and 12 h before ET injection and just before each
      pain test at 3, 6, 9 and 24 h after ET injection. At the dosages used,
      acetaminophen and dexamethasone were the most effective in reducing PP
      hyperalgesia and least effective on TF hyperalgesia, while indometacin and
      morphine produced their main effect on TF hyperalgesia. The four drugs were about
      equally effective in reversing HP hyperalgesia. We conclude that ET hyperalgesia
      is mediated by both prostaglandin-sensitive and prostaglandin-independent
      mechanisms.

PMID- 9286814
TI  - Stimulation of mucin metabolism in rat gastric mucosa by histamine.
AB  - We examined the effects of histamine on mucin localized in the different regions
      and layers of rat gastric mucosa by determining the changes in the content as
      well as the biosynthetic activity of the mucin. In vivo administration of 0.8
      mg/kg of histamine, which could not induce a concomitant gastric acid secretion,
      caused a significant increase in the mucin content in the corpus mucosa, but not
      in the antral mucosa. This increase was due to a significant accumulation of the
      mucin in the mucus gel and surface mucosa of the corpus region, whereas that in
      the deep mucosa did not significantly change. In the in vitro incubation system
      of rat gastric mucosa, histamine and dibutyryl cyclic AMP significantly increased
      [3H]-labeled mucin in the corpus. The histamine-induced acceleration of mucin
      biosynthesis was suppressed by ranitidine, but not pyrilamine. In the antrum, the
      biosynthetic activity showed no significant change by histamine. These results
      suggest that histamine promotes mucin metabolism via histamine H2 receptors in
      the surface mucosal layer of the corpus.

PMID- 9286815
TI  - Inhibitory effect of amitriptyline on contraction of the rat isolated trachea.
AB  - The effects of amitriptyline, a tricyclic antidepressant, on contractile
      responses to exogenously applied acetylcholine, endothelin 1 and high K+ were
      examined in the rat isolated trachea. Amitriptyline (0.3-30 mumol/l) produced a
      shift to the right of the logarithmic acetylcholine concentration-contraction
      curve without affecting the maximum contraction. Amitriptyline (10-100 mumol/l)
      significantly reduced the maximal contractile response to endothelin 1. The IC50
      values were 10.3 and 30.2 mumol/l for inhibition of the submaximal contractile
      response to 1 mmol/l acetylcholine and to 50 nmol/l endothelin 1, respectively.
      Amitriptyline inhibited the high K+ (60 mmol/l)-evoked contraction with an IC50
      of 0.225 mumol/l. The inhibitory effect of amitriptyline was unchanged by the K+
      channel blockers, charybdotoxin (100 nmol/l) and glibenclamide (up to 10
      mumol/l). These results indicate that amitriptyline could antagonize the effect
      of acetylcholine and also exert direct inhibitory effect on muscle contraction of
      the rat trachea as a nonselective muscle relaxant.

PMID- 9286816
TI  - Effects of various antiepileptic drugs on plasma levels of lamotrigine, a novel
      antiepileptic, in rats.
AB  - The pharmacokinetics of lamotrigine (LTG) and effects of carbamazepine (CBZ),
      valproic acid (VPA) and zonisamide (ZNS) on LTG kinetics were investigated in
      rats. LTG plasma levels were measured by high-performance liquid chromatography
      (HPLC). A single oral administration of LTG at 2.5-10 mg/kg showed linear
      disposition kinetics. In the pharmacokinetic parameters of LTG when combined with
      CBZ, the maximal plasma concentration (Cmax) and the area under the plasma
      concentration curve (AUC0-36) values were significantly lower and the time to
      maximal plasma concentration (Tmax) value was significantly higher than those in
      LTG alone. Furthermore, the Cmax and AUC0-36 values of LTG when pretreated with
      CBZ for 7 days were significantly lower than those from simultaneous treatment
      with CBZ. The Cmax and AUC0-36 values of LTG when combined with VPA were
      significantly lower than those for LTG alone. There was no significant difference
      in the Tmax or time of elimination half-life (t1/2) values of LTG between
      simultaneous and pretreatment with VPA. Of the pharmacokinetic parameters of LTG
      with ZNS combination, the Cmax value of LTG after long-term dosings of ZNS
      decreased significantly, whereas no significant change in Cmax was observed after
      the combined single administration of LTG and ZNS. Single and chronic ZNS
      treatment did not significantly affect the Tmax, t1/2 and AUC0-36 values of LTG.
      The LTG trough level was significantly reduced by CBZ administration, reached the
      bottom level at 6 days after starting CBZ administration, and recovered gradually
      after withdrawal of CBZ. These results suggest that CBZ, VPA and ZNS causes
      changes in the plasma LTG level. They also suggest that in therapy combining LTG
      with one of these antiepileptics, especially CBZ, the LTG concentration in plasma
      should be monitored carefully.

PMID- 9286817
TI  - Responsiveness of aortic rings of cadmium-hypertensive rats to endothelin-1.
AB  - Cadmium administered intraperitoneally at a dose of 1 mg/kg/day for 15 days
      caused a significant increase in mean arterial blood pressure. Endothelin-1 and
      noradrenaline produced concentration-dependent contractions of aortic rings that
      attained a lower maximal contraction in cadmium-injected rats as compared with
      control rats (p < 0.05). On the other hand, responses of aortic rings to
      different concentrations of potassium chloride did not show a significant
      difference between the groups. The decreased responsiveness of the aortae of
      cadmium-hypertensive rats to endothelin-1 and noradrenaline could either be due
      to an interaction of cadmium with receptors or intracellular signal transduction
      pathways of these agents, or it may simply reflect the adaptive changes in
      vascular tissues following hypertension development.

PMID- 9286818
TI  - A piece of my mind. Fanya kazi pamoja.

PMID- 9286819
TI  - PSA thresholds for prostate cancer detection.

PMID- 9286820
TI  - PSA thresholds for prostate cancer detection.

PMID- 9286821
TI  - PSA thresholds for prostate cancer detection.

PMID- 9286822
TI  - Regulating firearm advertisements.

PMID- 9286823
TI  - Regulating firearm advertisements.

PMID- 9286824
TI  - Regulating firearm advertisements.

PMID- 9286826
TI  - Tissue adhesives for laceration closure.

PMID- 9286825
TI  - Regulating firearm advertisements.

PMID- 9286827
TI  - Pericardial disease.

PMID- 9286828
TI  - Developing curricula to promote preventive medicine skills. The Teaching
      Immunization for Medical Education (TIME) Project. TIME Development Committee.
AB  - CONTEXT: Vaccines are underused in the United States, resulting in needless
      morbidity. Many experts have concluded that clinician education is critical to
      increasing the nation's vaccination rates. OBJECTIVE: To develop and evaluate
      case-based curricular materials on immunizations that promote preventive medicine
      skills. DESIGN: Before-and-after trial of an educational intervention. SETTING
      AND PARTICIPANTS: Medical schools and primary care residency programs from 20
      institutions across the United States participated in the Teaching Immunization
      for Medical Education (TIME) project. INTERVENTION: A multidisciplinary team
      developed learning objectives, abstracted clinical cases, and created case-based
      modules that use contextual learning and small-group interaction to solve
      clinical and public health problems. The case-based methods are multistation
      clinical teaching scenarios (MCTS) and problem-based learning (PBL). MAIN OUTCOME
      MEASURES: Knowledge gained by learners from pretest to posttest and the overall
      ratings of the sessions by learners and facilitators based on evaluation
      questionnaires. RESULTS: Pretest and posttest results were obtained on a total of
      1122 learners for all modules combined. For the MCTS method, mean scores
      increased from the 10-item pretest to the posttest by 3.1 items for measles, 3.8
      for influenza, 1.8 for hepatitis B, 3.9 for pertussis, 1.9 for adult vaccination,
      1.9 for childhood vaccination, and 2.6 for Haemophilus influenzae type b (P<.01
      for each). For the PBL method, mean scores increased by 3.4 items for measles,
      3.3 for influenza, 2.6 for hepatitis B, and 2.5 for pertussis (P<.01 for each).
      Most learners (MCTS, 98%; PBL, 89%) and most facilitators (MCTS, 97%; PBL, 100%)
      rated the sessions overall as very good or good. CONCLUSIONS: Use of TIME modules
      increases knowledge about immunizations, an essential step to improving
      vaccination practices of future clinicians. Given the realities of decreased
      faculty time and budgets, educators face major challenges in developing case
      based curricula that prepare learners for the 21st century. Nationally tested
      libraries of cases such as the TIME modules address this dilemma.

PMID- 9286829
TI  - Direct observation of community-based ambulatory encounters involving medical
      students.
AB  - CONTEXT: The current shift of predoctoral medical education from inpatient
      tertiary settings to community-based, ambulatory practice has raised questions
      about the effect of the medical student on the process of patient care.
      OBJECTIVE: To determine how the presence of a medical student during the
      ambulatory medical encounter affects the use of clinical time and patient
      satisfaction. DESIGN: Cross-sectional, multimethod study using direct observation
      of ambulatory care by research-trained nurses. SETTING: A total of 16 community
      based family practice offices accepting family practice clerkship students.
      PATIENTS: A total of 452 outpatient visits with and without student involvement.
      MAIN OUTCOME MEASURES: Clinical time use as measured by the Davis Observation
      Code; patient satisfaction was assessed with the Medical Outcomes Study 9-item
      visit rating scale. RESULTS: When students were involved, physicians spent more
      time discussing visit expectations (P=.03) and less time in history taking
      (P=.007), providing assessment (P=.01), and answering questions (P=.04). Despite
      these differences, patients were equally satisfied with explanations received,
      and there was no change in the rank order of the 5 most commonly observed
      physician behaviors. There was no difference in time spent in treatment planning,
      physical examination, health education, or social chatting. The physician spent
      equal time with the patient with (10.3 minutes) and without (9.9 minutes, P=.6)
      student involvement. There was no decrease in patient satisfaction when students
      were involved. Physicians were more likely to discuss another family member's
      problems when a student was present (P=.001). Students were directed to care for
      minority patients at a disproportionate rate (P=.001), controlling for
      confounding variables. CONCLUSIONS: Medical student involvement alters the
      content but not the duration of the ambulatory medical encounter. Application of
      validated measures indicate that students did not impair patient satisfaction or
      hinder the physicians' ability to ensure that patient expectations for the visit
      were met.

PMID- 9286831
TI  - Promotion criteria for clinician-educators in the United States and Canada. A
      survey of promotion committee chairpersons.
AB  - CONTEXT: Clinician-educators have concerns about their ability to be promoted and
      the criteria used by medical school promotion committees. OBJECTIVE: To discover
      the criteria and methods that medical school promotion committees use to make
      decisions about the promotion of clinician-educators. METHODS: In June 1996 we
      mailed a questionnaire to chairpersons of all medical school promotion committees
      in the United States and Canada. RESULTS: Of 142 schools surveyed, 115 (81%)
      responded; 45% of respondents had a clinician-educator promotion track. On a
      scale from 1 (minimally important) to 7 (extremely important), the mean
      importance ratings of aspects of clinician-educators' performance were the
      following: teaching skills (6.3), clinical skills (5.8), mentoring (5.7),
      academic administration (5.3), developing educational programs (5.3), nonresearch
      scholarship (5.1), clinical research (4.8), service coordination (4.7), and
      education research (4.5). Methods to evaluate each aspect of performance were
      rated by respondents for importance and frequency of use. The 4 most important
      methods for evaluating teaching were awards, peer evaluation, learner evaluation,
      and teaching portfolio; 70% or more of schools used these frequently or always.
      The 4 most important methods of evaluating clinical skills were peer evaluation,
      awards, trainee evaluation, and objective measures, which were used frequently or
      always by 78%, 65%, 58%, and 29% of schools, respectively. Clinician-educators
      were expected to have fewer peer-reviewed publications to be promoted than
      investigators (5.7 vs 10.6, P<.001). Schools with separate clinician-educator
      tracks differed little in survey responses from schools without such tracks.
      CONCLUSION: Most, but not all, promotion committees now assign high importance to
      the special contributions of clinician-educators and use a variety of methods to
      assess these, regardless of whether they have a separate clinician-educator
      promotion track.

PMID- 9286830
TI  - Cardiac auscultatory skills of internal medicine and family practice trainees. A
      comparison of diagnostic proficiency.
AB  - CONTEXT: Medical educators have had a growing sense that proficiency in physical
      diagnostic skills is waning, but few data have examined the question critically.
      OBJECTIVE, DESIGN, AND SETTING: To compare the cardiac auscultatory proficiency
      of medical students and physicians in training. A multicenter cross-sectional
      assessment of students and house staff. A total of 8 internal medicine and 23
      family practice programs of the mid-Atlantic area. PARTICIPANTS: A total of 453
      physicians in training and 88 medical students. INTERVENTIONS: All participants
      listened to 12 cardiac events directly recorded from patients, which they
      identified by completing a multiple-choice questionnaire. MAIN OUTCOME MEASURES:
      scores were expressed as the percentage of participants, for year and type of
      training, who correctly identified each event. Cumulative scores were expressed
      as the total number of events correctly recognized. An adjusted score was
      calculated whenever participants selected not only the correct finding but also
      findings that are acoustically similar and yet absent. RESULTS: Trainees'
      cumulative scores ranged between 0 and 7 for both internal medicine and family
      practice residents (median, 2.5 and 2.0, respectively). Internal medicine
      residents had the highest cumulative adjusted scores for the 6 extra sounds and
      for all 12 cardiac events tested (P=.01 and .02, respectively). On average,
      internal medicine and family practice residents recognized 20% of all cardiac
      events; the number of correct identifications improved little with year of
      training and was not significantly higher than the number identified by medical
      students. CONCLUSIONS: Both internal medicine and family practice trainees had a
      disturbingly low identification rate for 12 important and commonly encountered
      cardiac events. This study suggests a need to improve the teaching and assessment
      of cardiac auscultation during generalists' training, particularly with the
      advent of managed care and its search for more cost-effective uses of technology.

PMID- 9286832
TI  - The effects of the change in the NRMP matching algorithm. National Resident
      Matching Program.
AB  - CONTEXT: Following 2 years of heated controversy about the resident match, the
      National Resident Matching Program (NRMP) recently voted to replace the existing
      matching algorithm with a newly designed applicant-proposing algorithm.
      OBJECTIVE: To design an applicant-proposing algorithm for the match and compare
      it with the existing NRMP algorithm to determine how many applicants and
      residency programs could be expected to receive better or worse matches from the
      2 algorithms, how the different algorithms influence the opportunity for
      strategic behavior, and what advice can be given to participants. DESIGN:
      Computational experiments compared the newly designed applicant-proposing
      algorithm with the existing NRMP algorithm on the rank order lists (ROLs)
      submitted by all applicants and residency programs in the 1987 and 1993 through
      1996 NRMP matches. RESULTS: Differences in the matchings produced by the 2
      algorithms are small: fewer than 1 in 1000 applicants would have received a
      different match. Most (but not all) of the few applicants who are matched to
      different positions by the 2 algorithms do better when the applicant-proposing
      algorithm is used; the opposite is true for programs. Opportunities for
      profitable strategic behavior are very rare for both applicants and programs
      under either algorithm. With either algorithm, both applicants and programs can
      be advised that trying to get a preferred match by behaving strategically is far
      more likely to harm than to help them. CONCLUSIONS: The existing NRMP algorithm
      and the newly designed applicant-proposing algorithm perform similarly. Both
      algorithms make it sensible for applicants and residency programs to arrange
      their ROLs based solely on their preferences for possible matches. The choice of
      algorithms will systematically affect the matches of only a small group of
      applicants (<0.1%). The NRMP's recent decision to use the applicant-proposing
      algorithm starting in 1998 reflects a judgment about the impact of this
      difference on applicants and programs.

PMID- 9286833
TI  - Palliative care in undergraduate medical education. Status report and future
      directions.
AB  - OBJECTIVE: To describe the status of palliative care education in the
      undergraduate medical curriculum and to offer recommendations for improvement.
      DATA SOURCES: Review of literature on palliative care and of recently submitted
      grants on medical education for end-of-life care. STUDY SELECTION: English
      language reports of educational programs targeted toward medical students were
      examined, as well as surveys of medical schools. DATA EXTRACTION: Studies were
      reviewed by the authors to assess the quality of the educational program,
      evaluation methodology, and conclusions. From over 9000 citations on palliative
      care and related topics that were retrieved from MEDLINE searches from 1980
      through 1995, and from reviewing 14 palliative care journals published from 1985
      through 1996, 310 articles were identified that addressed medical education for
      end-of-life care, and 180 were carefully examined. DATA SYNTHESIS: While nearly
      all medical schools offer some formal teaching about end-of-life care, there is
      considerable evidence that current training is inadequate, most strikingly in the
      clinical years. Teaching about palliative care is received favorably by students,
      positively influences student attitudes, and enhances communication skills.
      However, curricular offerings are not well integrated; the major teaching format
      is the lecture; formal teaching is predominantly preclinical; clinical
      experiences are mostly elective; there is little attention to home care, hospice,
      and nursing home care; role models are few; and students are not encouraged to
      examine their personal reactions to these clinical experiences. CONCLUSIONS: The
      increasing attention to palliative care education has created major opportunities
      for improving education about care at the end of life. Educational programs
      should be rigorously evaluated to identify best educational practices.

PMID- 9286834
TI  - Temporary matters. The ethical consequences of transient social relationships in
      medical training.
AB  - Medical students and resident physicians spend much of their training engaged in
      transient, time-limited relationships with patients, families, and other care
      providers. This article offers a partial catalog of the problems that the
      evanescent nature of trainees' relationships with others creates in their lives,
      the strategies they often use to address these problems, and the deleterious
      consequences these strategies may have on their behavior and ethical development.

PMID- 9286835
TI  - Educational programs in US medical schools, 1996-1997.
AB  - We use data from the 1996-1997 Liaison Committee on Medical Education Annual
      Medical School Questionnaire, which had a 100% response rate, to describe medical
      education programs in the United States. In the 1996-1997 academic year, there
      were 95 568 full-time medical school faculty members, a 4.5% increase from 1995
      1996. In clinical departments, the largest increases were in emergency medicine
      (a 29% increase from 1995-1996) and family medicine (a 13% increase). Of all full
      time faculty members in clinical departments, 76.9% have an MD or DO as the
      highest degree, 4.5% have both an MD and PhD, 13.9% have a PhD, and 4.7% have an
      academic or professional bachelor's or master's degree as their final degree. The
      total number of applicants for the class entering in 1996 was 46968 (0.8%
      increase from 1995), while the number of first-time applicants decreased 1% from
      1995. First-year medical students who were members of underrepresented minority
      groups numbered 2236, a 4% decrease from 1995. In 1996-1997, the total number of
      medical students was 66712 (0.3% less than in 1995-1996). For students graduating
      during the 1995-1996 academic year, 13% took longer than 4 years to complete the
      program. There were 47 medical schools that reported that 1 or more hospitals
      used for required clinical clerkships had changed ownership, merged, or closed
      during 1996. Medical schools used an average of 6 (range, 1-36) hospitals for
      core clinical clerkship. Ninety-five schools required a passing grade on Step 1
      of the US Medical Licensing Examination (USMLE) for promotion or graduation; 54
      schools required a passing grade on Step 2 of the USMLE.

PMID- 9286836
TI  - US graduate medical education, 1996-1997.
AB  - Workforce planners continue to be concerned that unlimited growth in graduate
      medical education (GME)-principally fueled by unrestrained federal support-will
      lead to a physician surplus. Because of this concern, in 1996 six major
      professional organizations called for a reduction in Medicare support of GME to
      bring residency training programs into more rational alignment with population
      needs. As of July 1, 1997, no final action had been taken by Congress to limit
      GME funding, although extensive discussions are under way. Even without
      governmental restrictions, the American Medical Association's annual survey of
      GME programs showed a reduction in the numbers of first-year residents in most
      major specialties and subspecialties. Minor reductions were initially noticed
      last year; now, the decreases are significant. Nearly all the specialties that
      had difficulty placing their graduates for 2 consecutive years also reported at
      least 10% fewer first-year residents than in 1994. More importantly, disciplines
      without employment difficulties also reported downsizing. The overall effect of
      these first-year reductions is easily masked by the addition of programs in new
      disciplines and some residents staying in the GME system longer. Entry-level
      reductions appear to be broader and more extensive than can be explained by
      market forces alone.

PMID- 9286837
TI  - Review of US medical school finances, 1995-1996.
AB  - For the 1995-1996 fiscal year, all 125 accredited US medical schools responded to
      the annual medical school questionnaire of the Liaison Committee on Medical
      Education, part I-A. Using data from the financial portion of the questionnaire,
      we identify patterns of financing medical education during the past 3 years and
      the practice plan arrangements adopted by medical schools, including their
      organizational and legal structures. This financial review details differences in
      how public and private medical schools are being funded and funding changes
      during the past 3 years. The reported data show that revenues supporting medical
      school programs and activities totaled more than $31 billion in 1995-1996, an
      increase of 5.4% in inflation-adjusted dollars during the previous year. Compared
      with the previous year, revenues, in current and constant dollars, increased in
      almost every category in 1995-1996.

PMID- 9286840
TI  - Medical schools in the United States.

PMID- 9286838
TI  - Predominance of the curative model of medical care. A residual problem.

PMID- 9286839
TI  - The new match.

PMID- 9286842
TI  - Graduate medical education.

PMID- 9286841
TI  - Medical schools in Canada.

PMID- 9286843
TI  - Evaluating the evaluations.

PMID- 9286845
TI  - Assessing clinical performance with standardized patients.

PMID- 9286844
TI  - The dean's letter: improving the summary evaluation.

PMID- 9286846
TI  - Religion and spirituality in medicine: research and education.

PMID- 9286847
TI  - Pharmacologic and clinical perspectives on mibefradil: a new T-channel selective
      calcium antagonist: introduction.

PMID- 9286848
TI  - Pharmacologic and pharmacokinetic profile of mibefradil, a T- and L-type calcium
      channel antagonist.
AB  - Mibefradil is a recently introduced calcium antagonist that, as a tetralol
      derivative, is chemically distinct from previous calcium antagonists. This
      article will review pertinent results from in vitro, animal, and clinical
      investigations to report the pharmacologic properties that distinguish mibefradil
      from all of the calcium channel antagonists in use today, all of which operate on
      the "L-type" calcium channel. Mibefradil's pharmacokinetic profile indicates it
      can be used as a once-daily oral treatment for hypertension and chronic stable
      angina pectoris.

PMID- 9286849
TI  - Antihypertensive effects of mibefradil in the treatment of mild-to-moderate
      systemic hypertension.
AB  - This report summarizes the results of 4 double-blind, placebo-controlled studies
      designed to determine the efficacy, tolerability, and dose-response
      characteristics of the novel T-channel-selective calcium antagonist, mibefradil,
      in the treatment of mild-to-moderate essential hypertension. Two of these studies
      were conducted in the general population of essential hypertensives, 1 in elderly
      patients, and 1 in patients on chronic hydrochlorothiazide treatment. A total of
      1,116 patients were randomized to receive 1 of 7 doses of mibefradil (6.25-200
      mg; n = 927), or placebo (n = 189). Each study demonstrated a significant linear
      dose response in the reduction of sitting diastolic (SDBP) and sitting systolic
      (SSBP) blood pressure. In all 4 trials, SDBP was significantly reduced with the
      recommended doses of 50 and 100 mg mibefradil (placebo-corrected treatment
      effects of -4.1 to -6.8 mm Hg and -8.8 to -11.1 mm Hg, respectively, for the 50-
      and 100-mg doses). A similar reduction in SSBP occurred in 3 of 4 studies at the
      50-mg dose (-7.5 to -10.7 mm Hg) and in 4 of 4 studies at the 100-mg dose (-6.8
      to -16.7 mm Hg). Lower doses did not reduce blood pressure significantly; doses >
      100 mg had little additional effect and an increased incidence of adverse events.
      Overall, response and normalization rates were dose related and averaged 61% and
      51%, respectively, for the 50-mg dose and 78% and 65%, respectively, for the 100
      mg dose. The onset of the antihypertensive effect was gradual, with no first-dose
      effect; near maximal response was reached within 1-2 weeks. Trough/peak ratios
      ranged from 77-86% with the 50-mg dose and from 77-108% with the 100-mg dose,
      indicating a sustained effect over a 24-hour period. A slight decrease in heart
      rate was observed, ranging from -2.2 to -5.5 beats/min at the 50-mg dose and from
      -4.0 to -8.8 beats/min at the 100-mg dose. The efficacy and safety results were
      similar across all populations studied, including the elderly and
      hydrochlorothiazide-treated patients, indicating that no dose adjustment is
      needed for these populations. Thus, the results of these 4 placebo-controlled
      trials confirm that when taken at the recommended doses of 50 and 100 mg once
      daily, mibefradil is an effective, safe, and well-tolerated therapy for the
      treatment of mild-to-moderate hypertension.

PMID- 9286850
TI  - Antianginal and anti-ischemic effects of mibefradil in the treatment of patients
      with chronic stable angina pectoris.
AB  - Five placebo-controlled, double-blind, multicenter, parallel-design studies were
      performed to evaluate the antianginal and anti-ischemic characteristics of the
      novel T-channel-selective calcium antagonist, mibefradil, in the treatment of
      patients with chronic stable angina pectoris. Of the 5 studies, 2 were
      monotherapy dose-finding trials and 3 were conducted in patients receiving
      background antianginal therapy: either beta blockers (2 studies) or long-acting
      nitrates (1 study). A total of 865 patients were randomized to 1 of 4 mibefradil
      dose groups (25, 50, 100, and 150 mg; n = 565) and placebo (n = 300). The
      antianginal and anti-ischemic effects of mibefradil were assessed across all 5
      studies by evaluating exercise tolerance test variables, weekly number of anginal
      attacks and short-acting nitroglycerin consumption, and in both dose-finding
      studies, the number and total duration of silent ischemic episodes (48-hour
      Holter monitoring). A statistically significant increase in exercise duration was
      achieved in 3 of 5 studies with the 50-mg dose of mibefradil and in 3 of 3
      studies with the 100-mg dose of the compound over the effects observed in the
      placebo groups. A significant delay in time to onset of ischemia during exercise
      was induced in all studies with the 50- and 100-mg doses of mibefradil. The 25-mg
      dose of mibefradil was not significantly better than placebo, and the effects of
      the 150-mg dose of the compound were similar to those observed with the 100-mg
      dose. Across all studies, a dose-related decrease was observed in the number of
      weekly anginal attacks and in weekly nitroglycerin consumption. Similarly, a
      significant dose-related decrease in the number and duration of silent ischemic
      episodes was observed during Holter monitoring for 48 hours in the 2 dose-finding
      studies. The antianginal and anti-ischemic effects were associated with a dose
      related decrease in heart rate and double product both at rest and at exercise
      termination. Treatment with the 50- and 100-mg doses of mibefradil was found to
      be well tolerated and safe compared with placebo, a finding that held true for
      patients on chronic beta-blocker or long-acting nitrate therapy. Taken together,
      these studies indicate that mibefradil is an effective and well-tolerated once
      daily treatment for chronic stable angina pectoris at doses of 50 and 100 mg,
      which are the lowest and highest effective doses of the compound, respectively.

PMID- 9286852
TI  - Mibefradil in the treatment of chronic stable angina pectoris: comparative
      studies with other calcium antagonists.
AB  - The ability of mibefradil, a new T-channel-selective calcium antagonist, to
      improve exercise tolerance and silent ischemic parameters in patients with
      chronic stable angina was compared in 3 separate trials with 2 other commonly
      used calcium antagonists: diltiazem SR (120 mg/twice daily) and amlodipine (10
      mg/day). Compared with amlodipine, mibefradil 100 mg given once daily over a 3
      week period resulted in a statistically significantly larger increase from
      baseline in total exercise tolerance test (ETT) duration (treatment difference of
      40.9 sec, p = 0.04), time to onset of angina (treatment difference 61.2 sec, p <
      0.001), and time to onset of ischemia (treatment difference of 54.4 sec, p =
      0.004). The decrease in weekly anginal episodes was 58% with mibefradil versus
      19% with amlodipine, and the reduction in nitroglycerin consumption was 58% with
      mibefradil versus a 10% increase with amlodipine. The decrease in the number of
      silent ischemic episodes detected by a 48-hour Holter recording was significantly
      larger (p = 0.03) with mibefradil 100 mg (88%) compared with amlodipine 10 mg
      (38%). Similarly, a larger decrease in the duration of silent ischemia was
      observed with mibefradil (69%) compared with that seen with amlodipine (38%). The
      preliminary results of a second trial comparing mibefradil with amlodipine were
      consistent with the first demonstrating that the improvement for all 3 ETT
      parameters was larger for mibefradil (ETT duration: 55.2 sec; delay in onset
      angina: 74.2 sec; time to onset of ischemia: 63.6 sec), but in this trial the
      treatment differences did not reach statistical significance. In the trial
      comparing mibefradil (100 mg once daily) with diltiazem SR (120 mg twice daily),
      both compounds had equivalent effects on all ETT parameters tested. Mibefradil
      produced a 21% increase in exercise duration compared with a 20% increase with
      diltiazem. Although mibefradil yielded larger increases in the time to onset of
      angina and the time to onset of 1-mm ST-segment depression (42% and 38%,
      respectively) than did diltiazem (34% and 25%, respectively), the treatment
      differences did not reach statistical significance. Both mibefradil and diltiazem
      SR were associated with at least a 70% reduction from baseline in anginal
      frequency and nitroglycerin consumption. Mibefradil-treated patients showed
      greater decreases in heart rate and the rate-pressure product at each stage of
      the ETT than patients treated with amlodipine or diltiazem SR. All 3 drugs were
      well tolerated. However, compared with mibefradil, amlodipine and diltiazem SR
      produced a higher incidence of leg edema. In conclusion, the effectiveness of
      mibefradil in improving all 3 ETT parameters was greater than that of amlodipine
      and equivalent to that of diltiazem SR. Moreover, mibefradil provided greater
      reductions in the heart rate and cardiac workload than did the other 2 drugs.

PMID- 9286851
TI  - Mibefradil in the treatment of systemic hypertension: comparative studies with
      other calcium antagonists.
AB  - This paper summarizes the results of 4 double-blind studies of antihypertensive
      therapy in which mibefradil was compared with other commonly used calcium
      antagonists (diltiazem CD, amlodipine, nifedipine SR, and nifedipine GITS) at the
      recommended dose range. A total of 640 patients were included, with 361
      randomized to mibefradil, 98 to diltiazem CD, 119 to amlodipine, 71 to nifedipine
      SR, and 36 to nifedipine GITS. Trials included an active treatment phase of 6 or
      12 weeks in duration. Compared with diltiazem CD or nifedipine SR, mibefradil
      demonstrated statistically significant greater efficacy. Decreases in sitting
      diastolic blood pressure (SDBP) after treatment with mibefradil 100 mg once daily
      were 14.0 +/- 7.8 mm Hg compared with 9.5 +/- 7.5 mm Hg with diltiazem CD 360 mg
      once daily (p = 0.001), and 12.8 +/- 8.4 mm Hg compared with 8.1 +/- 19.2 mm Hg
      with nifedipine SR 40 mg twice daily (p = 0.014). Patients on mibefradil also had
      higher normalization (SDBP reduced to < or = 90 mm Hg) and response (SDBP
      reduction > or = 10 mm Hg or normalization) rates than did those on diltiazem CD
      or nifedipine SR. The overall incidence of adverse events was similar among these
      3 compounds, but the number of premature withdrawals due to adverse events was
      greater with both comparators than with mibefradil. Treatment with 100 mg
      mibefradil or 10 mg amlodipine once daily resulted in statistically significant
      decreases from baseline in SDBP of 11.5 +/- 8.2 mm Hg and 13.2 +/- 7.9 mm Hg,
      respectively, which were statistically equivalent. However, patients treated with
      amlodipine had a considerably greater incidence of leg edema than did those
      treated with mibefradil (33.6% vs 4.2%, respectively). Similarly, 100 mg
      mibefradil was equivalent in efficacy to 60 mg nifedipine GITS once daily, but
      patients on mibefradil experienced fewer vasodilatory related adverse events. In
      summary, mibefradil demonstrated superior efficacy to diltiazem CD and nifedipine
      SR and equivalent efficacy to amlodipine and nifedipine GITS in the treatment of
      hypertension.

PMID- 9286853
TI  - Safety of mibefradil, a new once-a-day, selective T-type calcium channel
      antagonist.
AB  - The safety and tolerability of mibefradil, a selective T-type calcium channel
      antagonist, were evaluated in 3,430 patients with essential hypertension and
      chronic stable angina pectoris treated in 15 double-blind placebo and active
      controlled clinical trials and 2 open-label, long-term safety studies. Of these
      patients, 2,636 were treated with the recommended doses of mibefradil (50 and 100
      mg) and form the basis of this report. With the 50-mg dose of mibefradil, the
      incidence of each adverse event was similar to, or lower than, that observed in
      the placebo-treated patients. Treatment with the 100-mg dose was associated with
      a slightly higher incidence compared to placebo of dizziness (2.1% vs 1.8%), leg
      edema (3.5% vs 1.4%), fatigue (2.1% vs 1.4%), and lightheadedness (2.1% vs 0.4%).
      The incidence of headache (4.6%) and angina pectoris (1.1%) was more frequent in
      patients treated with placebo. In active-controlled trials, a lower incidence of
      pedal edema (5.1%) was observed with mibefradil compared to amlodipine (25.7%),
      diltiazem SR/CD (9.4%), or nifedipine SR/GITS (17.4%). Overall, mibefradil was
      better tolerated than amlodipine and nifedipine SR/GITS and was as well tolerated
      as diltiazem SR/CD. Rates of premature discontinuation due to clinically adverse
      experiences with the 50- and 100-mg doses were 2.5% and 3.5%, respectively,
      compared with placebo (3.5%). No consistent pattern of laboratory adverse
      experiences were observed for mibefradil. Sinus bradycardia (heart rate <45
      beats/minute) and first-degree atrioventricular block were the only relevant
      treatment-emergent electrocardiographic changes that occurred more frequently
      with mibefradil than with placebo. No evidence of first-dose effects was observed
      in mibefradil-treated patients, and withdrawal effects were not observed in
      clinical trials. There were no clinically important differences in safety
      profiles in the demographic subgroups for age, gender, or race. The results of
      this comprehensive safety analysis indicate that treatment with the recommended
      doses of mibefradil is well tolerated and safe.

PMID- 9286854
TI  - Protein splicing: its chemistry and biology.
AB  - Protein splicing is a chemical reaction in which a spliced intervening
      polypeptide is excised from a precursor protein and the flanking N- and C
      terminal regions are ligated with the peptide bond to produce two mature
      proteins. This unique autocatalytic reaction was first discovered in the yeast
      VMA1 protein, a 120kDa spliced polypeptide encoded by the VMA1 gene of
      Saccharomyces cerevisiae. The VMA1 protein catalyses a self protein splicing post
      translationally to yield the 70 kDa catalytic subunit of the vacuolar H+-ATPase
      and the 50 kDa DNA endonuclease. Accumulating evidence has indicated that
      splicing precursors distribute widely in many organisms covering eukarya,
      bacteria and archaea. This article argues and summarizes current chemical and
      biological views on protein splicing.

PMID- 9286857
TI  - Diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A) controls the timing of cell
      division in Escherichia coli.
AB  - BACKGROUND: The timing of the cell division in Escherichia coli is highly
      regulated, but its mechanism has not been identified. Previously we have found
      that the cfcA1 mutation uncouples DNA replication and cell division and elevates
      the frequency of cell division. We further analysed the structure and the role of
      the cfc genes of cfcA11, a derivative of cfcA1, and another cfc mutant, cfcB1.
      RESULTS: The cfc mutants divided prior to the ordinary stage of cell division and
      produced many small cells with nucleoid. However, the cells grew exponentially,
      and the length of a cell cycle and the initiation mass for chromosome replication
      were not altered by the cfc mutations. These properties resulted from a reduction
      of the period between the nucleoid division and the cell division in a cell
      cycle, and a compensatory lengthening of the period between the cell division and
      the initiation of the next round of DNA replication. CfcA11 has a mutation in
      glySa which encodes the alpha-subunit of glycyl-tRNA synthetase, and cfcB1 has an
      IS2 insertion in apaH which encodes Ap4A hydrolase. The cfc properties of both
      cfc mutants were suppressed by a multicopy plasmid carrying apaH+, and the
      intracellular level of Ap4A in cfcA1 was 15-fold higher, and cfcB1 was 100-fold
      higher than their parent. Experiments using wild-type cells showed that a high
      level of Ap4A caused early cell division, and that a low level of Ap4A caused
      delayed cell division. CONCLUSION: Ap4A is a signal for the induction of cell
      division. High levels of Ap4A are responsible for the initiation of cell
      division. The glyS mutation permits an efficient synthesis of Ap4A.

PMID- 9286856
TI  - HsMCM6: a new member of the human MCM/P1 family encodes a protein homologous to
      fission yeast Mis5.
AB  - BACKGROUND: The tight regulatory mechanism that prevents more than one round of
      chromosomal DNA replication per cell cycle is thought to require the function of
      Mcm/P1 proteins. We report here the structural and functional analyses of HsMcm6,
      a human homologue of the Mis5 of Schizosaccharomyces pombe. RESULTS: We
      demonstrate here that the transcription of the HsMCM6 gene was repressed in
      quiescent cells but was rapidly induced at the G1/S phase by growth factor
      stimulation. The 5' regulatory region of the HsMCM6 gene was found to harbour
      four putative E2F binding motifs, and these were responsible for the promoter
      activity. The HsMcm6 protein level oscillated during the cell cycle, with a peak
      at the G1/S phase. We also showed that the cell-cycle dependent change of
      subcellular localization of HsMcm6 resembles those of other Mcm/P1 proteins.
      HsMcm6 consists of two forms, a form extractable by Nonidet P-40 and the nucleus
      bound form. A demonstration of the association of HsMcm6 with HsMcm2 and HsMcm7
      in vivo supports the idea that they behave as a heteromeric complex. We mapped
      the HsMCM6 gene at 2q12-14. CONCLUSION: The results indicate that the behaviour
      of HsMcm6 is reminiscent of replication licensing factor like other Mcm/P1 family
      members.

PMID- 9286855
TI  - Dynamics of chromosomes and microtubules visualized by multiple-wavelength
      fluorescence imaging in living mammalian cells: effects of mitotic inhibitors on
      cell cycle progression.
AB  - BACKGROUND: Mitotic events are accomplished by a coordinated interaction of
      molecular components within a cell. The continuous observation of specific
      molecular components in individual living cells provides a unique opportunity to
      examine the temporal and spatial coordination of these components. In order to be
      able to observe dynamic events in living mammalian cells, we have developed a
      computerized fluorescence microscope system. RESULTS: Using this fluorescence
      microscope system, we observed the dynamic behaviour of chromosomes and
      microtubules in living HeLa cells throughout an entire cell cycle. Chromosomes
      and microtubules were stained with Hoechst 33342 and rhodamine-conjugated
      tubulin, respectively. Microinjected rhodamine-tubulin was incorporated into
      microtubules at all stages of the cell cycle. In addition, rhodamine-tubulin
      stained the centrosomes during the G2 phase of the cell cycle and allowed us to
      observe centrosome movement. We also examined the effects of mitotic inhibitors
      on cell cycle progression. In a living cell treated with an inhibitor of type II
      DNA topoisomerase (ICRF-193) chromosomes formed an aberrant metaphase plate and
      failed to segregate. However, following mitotic spindle disassembly, the
      chromosomes decondensed normally. While the cell began to divide into two
      portions, cell division was eventually aborted and the daughter cells, still
      connected by a cytoplasmic bridge, rejoined into a single cell. These results
      demonstrate how a polyploid nucleus is generated in the presence of ICRF-193. On
      the other hand, microtubule polymerization inhibitors, such as colchicine,
      nocodazole and vinblastine, arrested the cell in the metaphase with condensed
      chromosomes; cytochalasin D did not affect the mitotic behaviour of either
      chromosomes or microtubules. CONCLUSIONS: Our observations of living cells
      demonstrate that the failure of chromosome segregation in and of itself does not
      prevent an exit from the metaphase, whereas the inhibition of microtubule
      assembly arrests cells at metaphase. Thus, a metaphase checkpoint is monitored by
      functional spindle microtubules but not by the completion of chromosome
      segregation.

PMID- 9286858
TI  - DAP-1, a novel protein that interacts with the guanylate kinase-like domains of
      hDLG and PSD-95.
AB  - BACKGROUND: The human homologue of the Drosophila discs large tumour suppressor
      protein (hDLG) and closely related proteins such as postsynaptic density protein
      95 kDa (PSD-95) are associated with N-methyl-D-aspartate receptors (NMDA-R) and
      Shaker-type K+ channels, and are thought to be involved in their clustering.
      RESULTS: We have identified a protein named DAP-1 that binds to the guanylate
      kinase-like domains of hDLG and PSD-95. DAP-1 was found to associate with hDLG,
      PSD-95, NMDA-R and adenomatous polyposis coli protein (APC). Furthermore, we
      found that DAP-1 is specifically expressed in the brain and colocalizes with PSD
      95 and APC in mouse cerebellum. We also found that DAP-1 is colocalized with PSD
      95 and NMDA-R at the synapses in cultured rat hippocampal neurons. CONCLUSION:
      Our findings suggest that DAP-1 may play several roles in the molecular
      organization of synapses and neuronal cell signalling by interacting with hDLG
      and PSD-95, which in turn are associated with receptors, ion channels and APC.

PMID- 9286860
TI  - The effect of behavioral states on fetal heart rate and middle cerebral artery
      flow-velocity waveforms in normal full-term fetuses.
AB  - OBJECTIVES: To evaluate the effect of fetal behavioral states on the relationship
      between fetal heart rate (FHR) and middle cerebral artery resistance index (MCA
      RI) in normal fetuses. METHODS: The FHR and MCA RI of 10 normal cases from 37 to
      40 weeks of gestation were recorded consecutively over a 45-min period.
      Correlations between the MCA RI and FHR during resting and active phases,
      classified by an actocardiotocogram, were analyzed by simple regression analysis.
      RESULTS: The mean FHR and MCA RI were significantly higher during the active
      phase (140.3 +/- 6.6 bpm, 0.79 +/- 0.06) than those during the resting phase
      (137.4 +/- 6.8 bpm, 0.75 +/- 0.07, P < 0.01, two sample t-test). There was a
      significant negative correlation (r = - 0.22, n = 2642, P < 0.01) between RI and
      FHR during the active phase and a significant positive correlation (r = 0.28, n =
      2066, P < 0.001) during the resting phase. CONCLUSIONS: The relationship between
      FHR and the MCA RI during the resting phase is different from during the active
      phase.

PMID- 9286859
TI  - Changes in leukocyte, granulocyte and lymphocyte counts following antenatal
      betamethasone administration to pregnant women.
AB  - OBJECTIVE: Preterm labor and premature rupture of membranes are associated with a
      mild leukocytosis. However, we have observed a higher maternal leukocyte count
      after antenatal betamethasone therapy. We planned this study to evaluate the
      effects of antenatal betamethasone treatment on maternal leukocyte, granulocyte
      and lymphocyte count. METHODS: Forty-six pregnant women with the diagnosis of
      preterm labor between 28 and 33 weeks of gestation age received 12 mg
      betamethasone at a 12-h interval. The control group consisted of 50 pregnant
      women between 28 and 33 weeks of gestational age with no medical or obstetrics
      problems. After a baseline venous sampling, serial leukocyte, granulocyte and
      lymphocyte counts were obtained every 6 h until it returned to baseline value.
      RESULTS: There were no statistically significant differences in the control group
      with respect to the total leukocyte, lymphocyte, and neutrophil count. Total
      leukocyte and granulocyte counts were increased by 29.8% and 17.8% within 24 and
      12 h after betamethasone injection, respectively (P < 0.01). A significant
      reduction in lymphocyte count was observed within 12 h (45.4%) after
      betamethasone injection (P < 0.01). All changes in leukocyte, granulocyte and
      lymphocyte counts returned to baseline values within 3 days. CONCLUSION:
      Antenatal betamethasone therapy leads to an increase in maternal leukocyte count
      and a decrease in lymphocyte count. This effect is transient and any leukocytosis
      persisting for more than 3 days is not due to betamethasone administration.

PMID- 9286861
TI  - Maternal and neonatal outcome related to delivery time following premature
      rupture of membranes.
AB  - OBJECTIVE: To evaluate neonatal and maternal outcomes of PROM deliveries with
      regard to the time elapsed since preterm rupture of membranes (PROM) to delivery.
      METHOD: According to the time elapsed since PROM to delivery we divided all
      singleton deliveries with PROM after the completed 34th week of gestation (N =
      35,419), which occurred in Slovenia between 1988 and 1994, into four groups:
      within 12 h, within 13-24 h, within 25-48 h, and over 48 h after PROM. The
      analysis was focused on the management of labor, neonatal and maternal infections
      and perinatal hypoxia with regard to the elapsed time. The Kruskal-Wallis
      analysis of variance, the Pearson chi-square test, Spearman rank correlation
      test, and the logistic regression test were used. RESULTS: With increasing time
      elapsed since PROM to delivery we found significantly increased incidences of
      induced labor, operative delivery, fetal distress, poorer fetal condition at
      birth, neonatal infections, and minor maternal infections. CONCLUSION: We may
      conclude that the best neonatal and maternal outcomes are obtained if delivery
      occurs within 12 h after PROM.

PMID- 9286862
TI  - Bone mass density in post-menopausal women.
AB  - OBJECTIVES: To evaluate the effect of age, years since menopause and body weight
      on bone mass density (BMD) in 283 patients. METHODS: Bone mass density was
      assessed by bone computerized mineralometry at two sites of the forearm. RESULTS:
      The mean distal BMD and ultra BMD in the postmenopausal group were negatively
      correlated with age (P < 0.001, r = -0.48 and P < 0.001, r = -0.50, respectively)
      and years since menopause (P < 0.001, r = -0.32 and P < 0.001, r = -0.33,
      respectively). When body-mass index was regressed against distal and ultra distal
      BMD, positive correlations were found (P = 0.008 and P = 0.007). CONCLUSIONS:
      From our data, forearm computerized mineralometry seems to be a reliable method
      for the evaluation of the effects of age and body-mass index on bone mass.

PMID- 9286863
TI  - Transvaginal ultrasonography and the progestogen challenge test in postmenopausal
      endometrial evaluation.
AB  - OBJECTIVE: To analyze the morphologic and ultrasonographic aspects of the
      endometrium of postmenopausal women according to the progestogen challenge test.
      METHODS: The study was conducted on 150 postmenopausal women. Each patient was
      submitted to transvaginal ultrasonography for measurement of endometrial echo
      thickness and to endometrial biopsies, followed by the progestogen challenge
      test. RESULTS: Women with a negative test presented atrophic endometrium in 94%
      of cases. The other 6% have shown active endometrium, but none had hyperplasia.
      However, 56% of the patients with a positive test had atrophic endometrium. There
      was a correlation between endometrial thickness less than 5 mm and endometrial
      atrophy in patients with either positive or negative tests. CONCLUSION: Because
      the progestogen challenge test is cheap and easy to deal with, it can be done as
      a primary screening method in asymptomatic postmenopausal women. If the test is
      positive, ultrasonography is required in order to determine who needs a more
      accurate examination of the endometrium. If the test is negative, ultrasonography
      is not required due to the great number of women who have atrophic endometrium.

PMID- 9286864
TI  - The Pryor technique of uterine morcellation.
AB  - OBJECTIVE: An efficient, yet largely forgotten technique of transvaginal uterine
      wedge morcellation developed by William Pryor at the turn of the century is
      described. METHOD: Pryor's technique of transvaginal wedge morcellation was
      employed to reduce uterine size in four cases of vaginal hysterectomy and in 10
      cases of laparoscopic-assisted vaginal hysterectomy in 14 patients with
      symptomatic uterine enlargement. RESULT: Operating time ranged from 49-170 min
      (mean 92 min). Estimated blood loss ranged from 150 to 480 ml (mean 225 ml).
      Uterine size ranged from 360-710 g (mean 455 g). No procedure required conversion
      to laparotomy. Primary indications for preliminary laparoscopy were confirmed in
      nine of 10 cases. No vaginal hysterectomy required subsequent laparoscopy. No
      patient required blood transfusion. No intra- or post-operative complications
      were noted. All patients were discharged home within 48 h post-surgery.
      CONCLUSION: Pryor's technique of wedge morcellation appears to be a safe and
      efficient method for the reduction of uterine size transvaginally.

PMID- 9286865
TI  - The outcome of radiation therapy in elderly patients with advanced cervical
      cancer.
AB  - OBJECTIVE: To clarify whether radiation therapy is a suitable treatment for
      elderly patients with advanced squamous cell carcinoma of the uterine cervix.
      METHOD: We investigated the outcome of 102 patients with stage IIIb squamous cell
      carcinoma of the uterine cervix, who underwent radiation therapy alone, by using
      a multiple regression analysis. RESULTS: All factors investigated were not
      significant prognostic variables in this study. Five-year survival rates between
      the two groups, which we have divided for every 5 years of age, showed no
      differences. CONCLUSION: Age was not a dependent prognostic factor in the
      patients with stage IIIb squamous cell carcinoma of the uterine cervix, if the
      subject underwent complete treatment. This study suggests that radiation therapy
      is still considered as a reasonable treatment for elderly patients with cervical
      cancer.

PMID- 9286866
TI  - Eclampsia--a taxing situation in the Third World.

PMID- 9286867
TI  - Cervical length in normal pregnancy as measured by transvaginal sonography.

PMID- 9286869
TI  - Ovarian malignancy in remnant ovarian tissue.

PMID- 9286868
TI  - Acoustic neuroma and twin pregnancy.

PMID- 9286870
TI  - Sacrococcygeal teratoma associated with a normal alpha-fetoprotein concentration.

PMID- 9286871
TI  - Rise of serum CA 125 in patients with pure ovarian yolk sac tumors.

PMID- 9286872
TI  - Cervical intra-epithelial neoplasia in HIV-positive women and women with AIDS.

PMID- 9286874
TI  - Asymmetry of the labia minora, uterus didelphys, unilateral imperforate vagina
      and other mullerian anomalies.

PMID- 9286873
TI  - Incidence levels for ovarian cancer in southern Ireland.

PMID- 9286875
TI  - Second-look operation in clear cell carcinoma of the ovary.

PMID- 9286876
TI  - ACOG educational bulletin. Antibiotics and gynecologic infections. American
      College of Obstetricians and Gynecologists. Number 237, June 1997 (Replaces No.
      153, March 1991).

PMID- 9286877
TI  - ACOG committee opinion. Hepatitis B immunization for adolescents. Number 184,
      June 1997. Committee on Adolescent Health Care. American College of Obstetricians
      and Gynecologists.

PMID- 9286878
TI  - ACOG criteria set. Quality evaluation and improvement in practice. Number 24,
      June 1997. Committee on Quality Assessment. American College of Obstetricians and
      Gynecologists.

PMID- 9286879
TI  - Ghostwriting in scientific anesthesia journals.

PMID- 9286880
TI  - The pharmacokinetics of intravenous fluids.

PMID- 9286881
TI  - Propofol requirements versus stimulus intensity.

PMID- 9286882
TI  - Keep the blood red...the right way.

PMID- 9286883
TI  - Volume kinetics of Ringer solution, dextran 70, and hypertonic saline in male
      volunteers.
AB  - BACKGROUND: A knowledge of the distribution of different fluids given by
      intravenous infusion is basic to the understanding of the effects of fluid
      therapy. Therefore, a mathematical model was tested to analyze the volume
      kinetics of three types of fluids. METHODS: The authors infused 25 ml/kg of
      Ringer acetate solution, 5 ml/kg of 6% dextran 70 in 0.9% NaCl, and 3 ml/kg of
      7.5% NaCl over 30 min in 8 male volunteers aged from 25 to 36 years (mean, 31
      years) and measured the changes in total hemoglobin, serum albumin, and total
      blood water over time. The changes were expressed as fractioned dilution and then
      plotted against time. The curves were fitted to a one-volume and a two-volume
      model, which allowed an estimation of the size of the body fluid space expanded
      by the fluid (V) and the elimination rate constant (k(r) to be made. RESULTS: The
      changes in blood water concentration indicated a mean size of V of 5.9 1 (+/-
      0.8, SEM) for Ringer's solution, 2.6 (+/- 0.3) 1 for dextran, and 1.2 (+/- 0.1) 1
      for hypertonic saline. The corresponding values of k(r) were 94 (+/- 42), 12 (+/-
      6), and 30 (+/- 4) ml/min, respectively. Blood hemoglobin indicated a degree of
      dilution similar to that indicated by blood water. Serum albumin indicated a more
      pronounced dilution, which resulted in a larger expandable volume and a greater
      mean square error for the curvefitting. The larger volume obtained for serum
      albumin can probably be explained by a loss of intravascular albumin into the
      tissues along with the infused fluid. CONCLUSIONS: The distribution of
      intravenous fluids can be analyzed by a kinetic model adapted for fluid spaces,
      but slightly different results are obtained, depending on the marker used to
      indicate dilution of the primary fluid space. Analysis and simulation of plasma
      volume expansion by this model is a tool that can help the anesthetist to better
      plan fluid therapy.

PMID- 9286884
TI  - Reduction by fentanyl of the Cp50 values of propofol and hemodynamic responses to
      various noxious stimuli.
AB  - BACKGROUND: Propofol and fentanyl infusion rates should be varied according to
      the patient's responsiveness to stimulation to maintain satisfactory anesthetic
      and operative conditions. However, somatic and autonomic responses to various
      noxious stimuli have not been investigated systematically for intravenous
      propofol and fentanyl anesthesia. METHODS: Propofol and fentanyl were
      administered via computer-assisted continuous infusion to provide stable
      concentrations and to allow equilibration between plasma-blood and effect-site
      concentrations. The propofol concentrations needed to suppress eye opening to
      verbal command and motor responses after 50-Hz electric tetanic stimulation,
      laryngoscopy, tracheal intubation, and skin incision in 50% or 95% of patients
      (Cp50 and Cp95) were determined at fentanyl concentrations of 0.0, 1.0, 2.0, 3.0,
      and 4.0 ng/ml in 133 patients undergoing lower abdominal surgery. The ability of
      propofol with fentanyl to suppress hemodynamic reactions in response to various
      noxious stimuli also was evaluated by measuring arterial blood pressure and heart
      rate before and after stimulation. RESULTS: The various Cp50 values for propofol
      alone (no fentanyl) for the various stimuli increased in the following order:
      Cp50loss of consciousness, 4.4 microg/ml (range, 3.8-5.0); Cp50tetanus, 9.3
      microg/ml (range, 8.3-10.4); Cp50laryngoscopy, 9.8 microg/ml (range, 8.9-10.8);
      Cp50skin incision, 10.0 microg/ml (range, 8.1-12.2); and Cp50intubation, 17.4
      microg/ml (range, 15.1-20.1; 95% confidence interval). The reduction of Cp50loss
      of consciousness, with fentanyl was minimal; 11% at 1 ng/ml of fentanyl and 17%
      at 3 ng/ml of fentanyl. A plasma fentanyl concentration of 1 ng/ml (3 ng/ml)
      resulted in a 31-34% (50-55%) reduction of the propofol Cp50s for tetanus,
      laryngoscopy, intubation, and skin incision. Propofol alone depresses
      prestimulation blood pressure but had no influence on the magnitude blood
      pressure or heart rate increase to stimulation. Propofol used with fentanyl
      attenuated the systolic blood pressure increases to various noxious stimuli in a
      dose-dependent fashion. CONCLUSIONS: The authors successfully defined the
      propofol concentration required for various stimuli. Tracheal intubation was the
      strongest stimulus. The absence of somatic reactions for propofol does not
      guarantee hemodynamic stability without fentanyl. Propofol with fentanyl was able
      to suppress motor and hemodynamic reactions to various noxious stimuli.

PMID- 9286885
TI  - Reduction in the incidence of carbon monoxide exposures in humans undergoing
      general anesthesia.
AB  - BACKGROUND: Carbon monoxide forms via reaction of isoflurane, enflurane, and
      desflurane with dried CO2 absorbents. The authors hypothesize that interventions
      by nonphysician support personnel to decrease absorbent drying will decrease the
      exposure rate of patients to carbon monoxide from anesthetic breakdown. METHODS:
      In the control group, all anesthetizing personnel were made aware of the factors
      enabling CO generation from anesthetic breakdown, and prevention techniques were
      left to the anesthetizing personnel. After data collection was complete, the
      following interventions were initiated to reduce absorbent drying: Anesthesia
      technicians and housekeeping personnel were instructed to turn off all anesthesia
      machines after the last case of the day in each room, and the CO2 absorbent was
      changed each morning if fresh gas was found flowing. Baralyme was used in all
      phases of this study. RESULTS: Five cases of intraoperative carbon monoxide
      exposure occurred among 1,085 (0.46%) first cases in the control group.
      Postintervention, patient carbon monoxide exposures decreased (P < 0.05), with
      one exposure among 1,961 (0.051%) first cases in the main operating room. Two
      exposures among 68 (2.9%) first cases occurred in remote locations (P < 0.001)
      versus main operating room. Predisposing factors for absorbent drying include the
      prolonged use of anesthesia machines for monitored anesthesia care, inappropriate
      drying techniques for expiratory flowmeters, understaffing of support personnel,
      and anesthesia in remote locations. CONCLUSIONS: These interventions reduced
      patient exposure to carbon monoxide. Monitoring for carbon monoxide exposures
      during general anesthesia may be necessary to recognize and end patient exposures
      that occur despite preventative measures.

PMID- 9286886
TI  - A comparison of remifentanil and morphine sulfate for acute postoperative
      analgesia after total intravenous anesthesia with remifentanil and propofol.
AB  - BACKGROUND: The transition from remifentanil intraoperative anesthesia to
      postoperative analgesia must be planned carefully due to the short duration of
      action (3-10 min) of remifentanil hydrochloride, a potent, esterase-metabolized
      mu-opioid agonist. This study compared the efficacy and safety of transition
      regimens using remifentanil or morphine sulfate for immediate postoperative pain
      relief in patients who had surgery under general anesthesia with
      remifentanil/propofol. METHODS: One hundred fifty patients who had received open
      label remifentanil and propofol for intraoperative anesthesia participated in
      this multicenter, double-blind, double-dummy study and were randomly assigned to
      either the remifentanil (R) group or the morphine sulfate (M) group. Twenty
      minutes before the anticipated end of surgery, the propofol infusion was
      decreased by 50%, and patients received either a placebo bolus (R group) or a
      bolus of 0.15 mg/kg morphine (M group). At the end of surgery, the propofol and
      remifentanil maintenance infusions were discontinued and the analgesic infusion
      was started: either 0.1 microg x kg(-1) x min(-1) remifentanil (R group) or
      placebo analgesic infusion (M group). During the 25 min after tracheal
      extubation, remifentanil titrations in increments of 0.025 microg x kg(-1) x min(
      1) and placebo boluses (R group), or 2 mg intravenous morphine boluses and
      placebo rate increases (M group) were administered as necessary at 5-min
      intervals to control pain. Patients received the 0.075 mg/kg intravenous morphine
      bolus (R group) or placebo (M group) at 25 and 30 min after extubation, and the
      analgesic infusion was discontinued at 35 min. From 35 to 65 minutes after
      extubation, both groups received 2-6 mg open-label morphine analgesia every 5 min
      as needed. RESULTS: Successful analgesia, defined as no or mild pain with
      adequate respiration (respiratory rate [RR] > or =8 breaths/min and pulse
      oximetry > or = 90%), was achieved in more patients in the R group than in the M
      group (58% vs. 33%, respectively) at 25 min after extubation (P < 0.05). The
      median remifentanil rate for successful analgesia was 0.125 microg x kg(-1) x
      min(-1) (range, 0.05-0.23 microg x kg(-1) x min(-1)), and the median number of 2
      mg morphine boluses used was 2 (range, 0-5 boluses). At 35 min after extubation,
      > or = 74% of patients in both groups experienced moderate to severe pain. Median
      recovery times from the end of surgery were similar between groups. Transient
      respiratory depression, apnea, or both were the most frequent adverse events (14%
      for the R group vs. 6% for the M group; P > 0.05). CONCLUSIONS: Remifentanil
      provided safe and effective postoperative analgesia when administered at a final
      rate of 0.05-0.23 microg x kg(-1) x min(-1) in the immediate postextubation
      period. Remifentanil provided more effective postoperative analgesia than did
      intraoperative treatment with morphine (0.15 mg/kg) followed by morphine boluses
      (< or = five 2-mg boluses). The effects of remifentanil dissipated rapidly after
      ending the infusion, and alternate analgesia was required. Further studies are
      underway to define transition regimens that will improve postoperative analgesia
      in patients receiving anesthesia with remifentanil.

PMID- 9286887
TI  - Twenty-four-hour pharmacokinetics of rectal acetaminophen in children: an old
      drug with new recommendations.
AB  - BACKGROUND: Rectal acetaminophen is often administered during operation to
      provide supplemental analgesia or antipyresis in children. Recent studies
      examining current dose guidelines are limited by short sampling times. The
      authors extended the drug sampling period to more clearly define acetaminophen
      pharmacokinetics in children having surgery. METHODS: Children (n = 28) were
      randomized to receive a single dose of 10, 20, or 30 mg/kg rectal acetaminophen
      after induction of anesthesia. Venous blood samples were taken every 30 min for 4
      h, every 60 min for 4 h, and every 4 h for 16 h. Data were analyzed using a mixed
      effects modeling technique (using NONMEM software) to determine the volume of
      distribution and clearance normalized for bioavailability. Additional models
      accounted for suppository dissolution followed by acetaminophen absorption.
      RESULTS: Age, weight, estimated blood loss, volume of intravenous fluid
      administered, and anesthesia time were similar in the three groups. Most patients
      did not achieve peak or sustained serum values in the 10-20 microg/ml serum
      concentration range associated with antipyresis. The volume of distribution was
      385 ml/kg, and clearance normalized for bioavailability, F, was 5.46 ml x kg(-1)
      x min(-1). Pharmacokinetic models suggest that absorption of acetaminophen is a
      function of zero-order dissolution of suppositories and first-order absorption
      from the rectum. Suppository dose size also may affect absorption
      characteristics. CONCLUSIONS: The current recommended rectal acetaminophen dose
      of 10-15 mg/kg yields peak serum concentrations less than the antipyretic serum
      concentration of 10-20 microg/ml. Based on the observed kinetics, the authors
      recommend that the initial dose should be approximately 40 mg/kg.

PMID- 9286888
TI  - Dose comparison of remifentanil and alfentanil for loss of consciousness.
AB  - BACKGROUND: This study evaluated the efficacy and safety of remifentanil, a
      potent mu agonist opioid with a rapid onset and offset of effect, as a sole
      induction agent for loss of consciousness (LOC) and compared it with alfentanil.
      METHODS: Remifentanil and alfentanil were administered intravenously over 2 min
      in ascending doses (remifentanil 2, 3, 4, 5, 6, 8, 10, 15, 20 microg/kg;
      alfentanil 40, 60, 80, 100, 120, 160, 200 microg/kg) to unpremedicated healthy
      patients. Patients were observed for rigidity and LOC for 30 s after the end of
      infusion. If patients had not lost consciousness, 2 mg x kg(-1) x min(-1)
      thiopental was administered until LOC was achieved. Arterial blood samples,
      obtained at specified time intervals, were analyzed for remifentanil and
      alfentanil whole-blood concentration. Blood pressure and heart rate were also
      recorded at preset time intervals. RESULTS: Neither drug could reliably produce
      LOC. With both drugs, there was a dose-dependent decrease in thiopental
      requirements and a dose-dependent increase in the incidence and severity of
      rigidity (P < 0.05). The median effective dose (ED50) for LOC with remifentanil
      was 12 microg/kg, and for alfentanil it was 176 mcrog/kg. The median effective
      concentration (EC50; whole-blood concentration) of remifentanil was 53.8 ng/ml
      and for alfentanil it was 1,012 ng/ml. Minimal hemodynamic changes were observed
      after either drug was given. CONCLUSIONS: Remifentanil is 15 times more potent
      than alfentanil, based on the ED50 to achieve loss of response to a verbal
      command and 20 times more potent than alfentanil based on the EC50. Neither
      opioid is suitable as a sole induction agent.

PMID- 9286889
TI  - A study of desmopressin and blood loss during spinal fusion for neuromuscular
      scoliosis: a randomized, controlled, double-blinded study.
AB  - BACKGROUND: Studies examining the use of desmopressin acetate (DDAVP) have shown
      variable results in DDAVP's efficacy for reducing blood loss. Studies of adults
      having cardiac surgery and of children having spinal fusion have suggested that
      patients with complicated medical histories and complex surgical procedures may
      benefit from use of DDAVP. Therefore, this study was designed to examine the
      homeostatic effects of DDAVP in children with severe cerebral palsy undergoing
      spinal fusion. METHODS: A randomized, double-blinded, and placebo-controlled
      trial of DDAVP was designed to enroll 40 patients. However, termination of the
      study was advised by the Institutional Review Board after 21 patients were
      enrolled. All patients had spastic quadriplegic-type cerebral palsy and were
      randomly assigned to one of two groups. The DDAVP group received 0.3 microg/kg
      DDAVP in 100 ml normal saline, and the placebo group received normal saline
      alone. All patients were anesthetized with nitrous oxide, oxygen, isoflurane, and
      fentanyl. Factor VIIIC and von Willebrand's factor (vWF) concentrations were
      measured in blood drawn before DDAVP infusion and 1 h after infusion. Blood
      pressure was maintained at a systolic pressure of less than 100 mmHg. Use of
      crystalloids, packed erythrocytes, platelets, and fresh frozen plasma were based
      on criteria established by protocol. Estimated blood loss was assessed by
      weighing sponges and measuring suctioned blood from canisters. RESULTS: Estimated
      blood loss (intraoperative and postoperative) and amount of packed erythrocytes
      transfused were similar for the DDAVP and placebo groups. Concentrations of both
      factor VIIIC and vWF were significantly greater after DDAVP infusion when
      compared with concentrations after placebo infusion. CONCLUSIONS: In the children
      who had complex spinal fusion, there was no difference in estimated blood loss
      between those who received DDAVP and those who received a placebo. Administration
      of DDAVP significantly increased factor VIIIC and vWF levels.

PMID- 9286890
TI  - Diagnosis of ventilator-associated pneumonia: an evaluation of direct examination
      and presence of intracellular organisms.
AB  - BACKGROUND: Ventilator-associated pneumonia (VAP) requires early diagnosis and
      adequate antibiotic therapy. The aim of this prospective postmortem study was to
      assess the accuracy of direct examination and quantification of intracellular
      organisms (ICO) for the diagnosis of VAP. METHODS: Total and differential cell
      counts were performed on fluids recovered using nonbronchoscopic sampling
      techniques (blind bronchial sampling [BBS], mini-bronchoalveolar lavage [mini
      BAL]) and from bronchoalveolar lavage (BAL) performed during fiberscopy. These 3
      sampling techniques were done within 15 min of death without discontinuing
      mechanical ventilation. Quantification of ICO was performed on each sample
      recovered from the various sampling procedures. Gram reaction and morphology of
      bacteria were evaluated on Gram smears. RESULTS: The results of each technique
      were compared with histology and culture of lung tissue specimens obtained by
      surgical pneumonectomies in 28 patients who died after at least 72 h of
      mechanical ventilation. Histology was positive in 13 patients and negative in 15
      patients. When only VAP with positive lung culture was considered (histologic
      signs of bronchopneumonia plus positive lung tissue culture), the sensitivity of
      Gram staining on BAL, mini-BAL, and BBS was 56%, 44%, and 56%, respectively. If
      all samples were considered, the sensitivity and the specificity of the
      determination of the percentage of ICO were low (less than 70%) whatever the
      sampling technique. CONCLUSIONS: For initial therapeutic guidance, direct
      examination and presence of ICO do not contribute for establishing the diagnosis
      of VAP, essentially because of a lack of sensitivity. However, when positive,
      Gram staining can obviously guide initial antibiotherapy.

PMID- 9286891
TI  - Dose-range effects of clonidine added to lidocaine for brachial plexus block.
AB  - BACKGROUND: Although addition of clonidine to local anesthetics can prolong pain
      relief after peripheral nerve block, a dose-range effect has not been determined.
      METHODS: Fifty-six outpatients undergoing carpal tunnel release were randomly
      assigned to receive in a double-blind fashion 45 ml of a mixture containing
      either 400 mg lidocaine plus saline or 400 mg lidocaine plus 30, 90 or 300 microg
      clonidine for axillary nerve block. In each group (n = 14), blocks were evaluated
      at regular time intervals to determine sensory and motor functions in the five
      nerve regions of the hand and forearm. Also, adequacy of the block for surgery,
      postoperative pain intensity, and side effects were evaluated. RESULTS: Compared
      with saline, each dose of clonidine reduced the onset time of sensory block and
      extended the field of adequate anesthesia. Ten minutes after injection, 30 microg
      clonidine was more effective than 90 microg clonidine in producing sensory
      blockade. Sedation occurred with clonidine 30 and 300 microg. Clonidine reduced
      the use of supplementary intravenous anesthetic agents for surgery and produced
      dose-dependent prolongation of analgesia, reaching a mean 770 min (range, 190
      1440 min) for the largest dose. Clonidine also produced a dose-dependent decrease
      in systolic arterial pressure of up to -22.5% (range, -6.0 29.9%) of baseline.
      With clonidine, 300 microg, three patients had mean arterial pressure of <55
      mmHg; four patients had episodes of arterial oxyhemoglobin saturation of <90%,
      and two others were not discharged because of hypotension. CONCLUSION: This study
      suggests that a small dose of clonidine enhances the quality of the peripheral
      blocks from lidocaine and limits the classical alpha2-agonist side effects to
      sedation.

PMID- 9286892
TI  - Oral clonidine premedication does not alter the efficacy of simulated intravenous
      test dose containing low dose epinephrine in awake volunteers.
AB  - BACKGROUND: Clonidine premedication modifies the hemodynamic responses to
      sympathomimetics. The present study was designed to test whether clonidine
      altered the response to a small intravenous dose of epinephrine, such as that
      which might be used in an epidural test dose. METHODS: In 18 healthy volunteers,
      four series of determinations were performed in random order and were separated
      by a minimum 72 h: (1) no premedication followed by intravenous saline 3 ml, (2)
      no premedication followed by intravenous test dose containing 3 ml of 1.5%
      lidocaine + 15 microg epinephrine, (3) oral clonidine (5 microg/kg 1.5 h before
      hemodynamic determinations) followed by intravenous saline, and (4) oral
      clonidine followed by intravenous epinephrine-containing test dose. Systolic
      blood pressure (SBP) and heart rate (HR) were measured continuously, and symptoms
      associated with central nervous system toxicity were noted. RESULTS: After the
      test dose injections, HR and SBP increased with or without clonidine
      premedication. The 95% confidence intervals for the maximum HR increases with and
      without clonidine were 49-61 and 44-54 beats/min, respectively, indicating that
      one could not be absolutely certain that everyone would develop a positive HR
      response. The HR increase was > or = 20 beats/min in 18 of 18 volunteers given
      epinephrine with or without clonidine and in 0 of 18 volunteers given saline.
      Calculated sensitivities, specificities, and positive and negative predictive
      values were all 100% based on the conventional HR criterion and were unaltered by
      clonidine. Subjective symptoms were not affected by clonidine. CONCLUSIONS: Oral
      clonidine does not alter the efficacy of epinephrine-containing test doses used
      for detecting intravascular injection.

PMID- 9286893
TI  - Influence of acute pain induced by activation of cutaneous nociceptors on
      ventilatory control.
AB  - BACKGROUND: Although many studies show that pain increases breathing, they give
      little information on the mechanism by which pain interacts with ventilatory
      control. The authors quantified the effect of experimentally induced acute pain
      from activation of cutaneous nociceptors on the ventilatory control system.
      METHODS: In eight volunteers, the influence of pain on various stimuli was
      assessed: room air breathing, normoxia (end-tidal pressure of carbon dioxide
      (PET(CO2)) clamped, normoxic and hyperoxic hypercapnia, acute hypoxia, and
      sustained hypoxia (duration, 15-18 min; end-tidal pressure of oxygen,
      approximately 53 mmHg). Noxious stimulation was administered in the form of a 1
      Hz electric current applied to the skin over the tibial bone. RESULTS: While
      volunteers breathed room air, pain increased ventilation (V(I)) from 10.9 +/- 1.7
      to 12.9 +/- 2.5 l/min(-1) (P < 0.05) and reduced PET(CO2) from 38.3 +/- 2.3 to
      36.0 +/- 2.3 mmHg (P < 0.05). The increase in V(I) due to pain did not differ
      among the different stimuli. This resulted in a parallel leftward-shift of the
      V(I)-carbon dioxide response curve in normoxia and hyperoxia, and in a parallel
      shift to higher V(I) levels in acute and sustained hypoxia. CONCLUSIONS: These
      data indicate that acute cutaneous pain of moderate intensity interacted with the
      ventilatory control system without modifying the central and peripheral
      chemoreflex loop and the central modulation of the hypoxia-related output of the
      peripheral chemoreflex loop. Pain causes a chemoreflex-independent tonic
      ventilatory drive.

PMID- 9286894
TI  - Physiologic determinants of the response to inhaled nitric oxide in patients with
      acute respiratory distress syndrome.
AB  - BACKGROUND: The response to inhaled nitric oxide (NO) in patients with acute
      respiratory distress syndrome (ARDS) varies. It is unclear which patients will
      respond favorably and whether the initial response persists over time. The
      authors defined a clinically useful response to inhaled NO as an increase of more
      than 20% of the ratio of the partial pressure of oxygen (Pa(O2)) to the
      inspiratory fraction of oxygen (FIO2), a decrease of more than 20% of pulmonary
      vascular resistance, or both. The authors hypothesized that patients who
      initially respond favorably are likely to show persistent improvements of gas
      exchange and hemodynamics after 48 h of NO inhalation. METHODS: The medical
      records and collected research data of 88 patients with ARDS who received 92
      trials of NO inhalation between March 1991 and February 1996 were reviewed.
      RESULTS: Fifty-three of the 92 trials (58%) produced a clinically significant
      response to NO. In the responding patients who continued to receive NO therapy (n
      = 43), the Pa(O2)/FiO2 ratio remained higher (120 +/- 46 vs. 89 +/- 32 mmHg
      before NO; P < 0.01) and the mean pulmonary artery pressure remained lower (35 +/
      8 vs. 40 +/- 12 mmHg before NO; P < 0.01) at 48 h. Only 33% of the patients with
      septic shock responded to inhaled NO compared with 64% of those without septic
      shock (P < 0.02). CONCLUSIONS: Most patients with ARDS had clinically useful
      responses to NO inhalation. Patients with an initial favorable response
      maintained the improvement at 48 h. Patients with septic shock were less likely
      to respond favorably.

PMID- 9286895
TI  - High carboxyhemoglobin concentrations occur in swine during desflurane anesthesia
      in the presence of partially dried carbon dioxide absorbents.
AB  - BACKGROUND: Increased carboxyhemoglobin concentrations in patients receiving
      inhalation anesthetics (desflurane, enflurane, and isoflurane) have been
      reported. Recent in vitro studies suggest that dry carbon dioxide absorbents may
      allow the production of carbon monoxide. METHODS: The authors used high fresh
      oxygen flow (5 or 10 l/min) through a conventional circle breathing system of an
      anesthesia machine for 24 or 48 h to produce absorbent drying. Initial studies
      used 10 l/min oxygen flow with the reservoir bag removed or with the reservoir
      bag left in place during absorbent drying (this increases resistance to gas flow
      through the canister). A third investigation evaluated a lower flow rate (5
      l/min) for absorbent drying. Water content of the absorbent and temperature were
      measured. Pigs received a 1.0 (human) minimum alveolar concentration desflurane
      anesthetic (7.5%) for 240 min using a 1 l/min oxygen flow rate with dried
      absorbent. Carbon monoxide concentrations in the circuit and carboxyhemoglobin
      concentrations in the pigs were measured. RESULTS: Pigs anesthetized with
      desflurane using Baralyme exposed to 48 h of 10 l/min oxygen flow (reservoir bag
      removed) had extremely high carboxyhemoglobin concentrations (more than 80%).
      Circuit carbon monoxide concentrations during desflurane anesthesia using
      absorbents exposed to 10 l/min oxygen flow (reservoir bag removed, 24 h) reached
      peak values of 8,800 to 13,600 ppm, depending on the absorbent used.
      Carboxyhemoglobin concentrations reached peak values of 73% (Baralyme) and 53%
      (soda lime). The water content of Baralyme decreased from 12.1 +/- 0.3% (mean +/-
      SEM) to as low as 1.9 +/- 0.4% at the bottom of the lower canister (oxygen flow
      direction during drying was from bottom to top). Absorbent temperatures in the
      bottom canister increased to temperatures as high as 50 degrees C. With the
      reservoir bag in place during drying (10 l/min oxygen flow), water removal from
      Baralyme was insufficient to produce carbon monoxide (lowest water content =
      5.5%). Use of 5 l/min oxygen flow (reservoir bag removed) for 24 h did not reduce
      water content sufficiently to produce carbon dioxide with desflurane.
      CONCLUSIONS: An oxygen flow rate of 10 l/min for 24 h in a conventional
      anesthesia circuit can dry carbon dioxide absorbents sufficiently to produce
      extremely high levels of carbon monoxide with high carboxyhemoglobin
      concentrations in desflurane-anesthetized pigs. When the reservoir bag is in
      place on the anesthesia machine or when a lower oxygen flow rate (5 l/min) is
      used, carbon dioxide absorbent drying still occurs, but 24-48-h exposure time is
      insufficient to allow for carbon monoxide production with desflurane.

PMID- 9286896
TI  - Isobolographic analysis of interactions between intravenous morphine,
      propacetamol, and diclofenac in carrageenin-injected rats.
AB  - BACKGROUND: It has been suggested that the combination of analgesic drugs may
      have additive or synergistic effects. In clinical practice, this might allow
      better analgesia and reduction of side effects. METHODS: The effects of analgesic
      drugs were studied in a model of acute inflammatory pain in carrageenin-injected
      rats using the vocalization threshold to paw pressure. A combination of three
      different intravenous drugs were used: morphine, diclofenac, and propacetamol, a
      pro-drug of acetaminophen. The dose-response curves were first obtained for each
      drug alone. The analgesic potencies of the combinations of morphine and
      diclofenac (ratios, 1:5.66 and 1:10), morphine and propacetamol (ratio, 1:250),
      and diclofenac and propacetamol (ratio, 1:65.7) were thereafter evaluated and
      compared with the effects of the drugs alone. RESULTS: For the two different
      ratios tested, synergy between diclofenac and morphine was observed only with the
      higher doses. Propacetamol and morphine or diclofenac and propacetamol
      combinations were additive for all doses tested. CONCLUSIONS: This study found a
      synergy between intravenous morphine and diclofenac that is consistent with and
      helps explain the clinical value of this type of combination in the treatment of
      acute pain in humans.

PMID- 9286897
TI  - Effect of intravenous anesthetics on inward rectifier potassium current in rat
      and human ventricular myocytes.
AB  - BACKGROUND: Inhibition of the inward rectifying potassium current (I(K1)) may
      cause cardiac dysrhythmias by decreasing resting membrane potential or prolonging
      action potential. METHODS: The effects of thiopental, ketamine, and propofol on
      I(K1) conductance were evaluated in rat ventricular myocytes. The effect of
      thiopental on I(K1) conductance was also evaluated in human ventricular myocytes.
      Currents were recorded using the nystatin-perforated whole-cell patch-clamp
      technique (holding potential, -50 mV; test potentials, -140 to -40 mV). Pipette
      solution contained 130 mM KCl, 5 mM MgCl2, 5 mM HEPES, and 5 mM EGTA,pH 7.2. Bath
      solution (32 degrees C) contained 134 mM NaCI, 4 mM KCl, 1 mM MgCl2, 1 mM CaCl2,
      0.3 mM CdCl2, 5 mM HEPES, and 5 mM d-glucose,pH 7.4. Drug concentrations examined
      encompassed the range of clinically relevant unbound plasma concentrations.
      Currents were normalized for cell capacitance. Conductance was calculated as
      current density/delta mV from -140 to -100 mV. Analysis of variance was used to
      test for changes in conductance as a function of drug concentration. RESULTS:
      Thiopental reduced I(K1) conductance in a concentration-dependent manner (P <
      0.0001). Thiopental-induced changes in I(K1) conductance in rat ventricular
      myocytes were fit to an inhibitory E(max) model, with a median inhibitory
      concentration of 10.5 microM. The effect of thiopental on I(K1) conductance in
      human ventricular cells was comparable to that observed in rat ventricular
      myocytes. Neither ketamine nor propofol altered I(K1) conductance. CONCLUSIONS:
      Thiopental reduces I(K1) conductance in a concentration-dependent manner at
      clinically relevant concentrations in both rat and human ventricular myocytes.

PMID- 9286899
TI  - Comparative effects of hypotension due to isoflurane, nitroglycerin, and
      adenosine on subendocardial microcirculation: observation of the in situ beating
      swine heart under critical stenosis.
AB  - BACKGROUND: Although isoflurane may cause subendocardial hypoperfusion in the
      presence of coronary stenosis because of its coronary arteriolar dilatory
      effects, it is not known how the subendocardial microcirculation is affected. The
      authors examined the effects of isoflurane on poststenotic subendocardial
      microvessels with coronary stenosis. METHODS: The authors observed subendocardial
      microvessels in in situ beating swine hearts with or without critical stenosis of
      the left anterior descending coronary artery (LAD) with a needle-type
      videomicroscope during isoflurane- (ISO-H), adenosine- (ADE-H), and nitroglycerin
      (NTG-H) induced hypotension (mean arterial pressure, 55 mmHg). Regional
      myocardial function, oxygen balance, and lactate metabolism in the region
      perfused by the LAD also were determined. RESULTS: In swine with stenosis, there
      were no differences in heart rate, cardiac output, and LAD blood flow among the
      three types of hypotension. Regional lactate production and anterior
      interventricular venous pO2 were similar during ISO-H and NTG-H but higher during
      ADE-H. With videomicroscopy, about half as many subendocardial microvessels could
      be visualized during ADE-H as with ISO-H and NTG-H. The average decrease in the
      systolic diameter of subendocardial microvessels of greater than 100 microm was 9
      +/- 6% during ISO-H and 12 +/- 5% during NTG-H, but no consistent phasic diameter
      changes were observed during ADE-H. In swine without stenosis, a systolic
      diameter decrease was observed during all three types of hypotension.
      CONCLUSIONS: These findings suggest that hypotension induced by isoflurane or
      nitroglycerin preserves phasic diameter changes in subendocardial microvessels in
      the presence of critical coronary stenosis, whereas that induced by adenosine
      does not.

PMID- 9286898
TI  - Pulmonary blood flow distribution in sheep: effects of anesthesia, mechanical
      ventilation, and change in posture.
AB  - BACKGROUND: Recent studies providing high-resolution images of pulmonary
      perfusion have questioned the classical zone model of pulmonary perfusion. Hence
      the present work was undertaken to provide detailed maps of regional pulmonary
      perfusion to examine the influence of anesthesia, mechanical ventilation, and
      posture. METHODS: Pulmonary perfusion was analyzed with intravenous fluorescent
      microspheres (15 microm) in six sheep studied in four conditions: prone and
      awake, prone with pentobarbital-anesthesia and breathing spontaneously, prone
      with anesthesia and mechanical ventilation, and supine with anesthesia and
      mechanical ventilation. Lungs were air dried at total lung capacity and sectioned
      into approximately 1,100 pieces (about 2 cm3) per animal. The pieces were weighed
      and assigned spatial coordinates. Fluorescence was read on a spectrophotometer,
      and signals were corrected for piece weight and normalized to mean flow.
      Pulmonary blood flow heterogeneity was assessed using the coefficient of
      variation of flow data. RESULTS: Pentobarbital anesthesia and mechanical
      ventilation did not influence perfusion heterogeneity, but heterogeneity
      increased when the animals were in the supine posture (P < 0.01). Gravitational
      flow gradients were absent in the prone position but present in the supine (P <
      0.001 compared with zero). Pulmonary perfusion was distributed with a hilar-to
      peripheral gradient in animals breathing spontaneously (P < 0.05). CONCLUSIONS:
      The influence of pentobarbital anesthesia and mechanical ventilation on pulmonary
      perfusion heterogeneity is small compared with the effect of changes in posture.
      Analysis of flow gradients indicate that gravity plays a small role in
      determining pulmonary blood flow distribution.

PMID- 9286900
TI  - Effects of blood glucose changes and physostigmine on anesthetic requirements of
      halothane in rats.
AB  - BACKGROUND: Although hyper- and hypoglycemia induce neurophysiologic changes,
      there have been no reports on the effects of blood glucose changes on anesthetic
      requirements. This study examined the effects of hyper- and hypoglycemia on the
      minimum alveolar concentration (MAC) of halothane in rats. In addition, based on
      a previous finding that the level of brain acetylcholine was reduced during mild
      hypoglycemia, the authors examined the influence of physostigmine on MAC during
      hypoglycemia. METHODS: In Sprague-Dawley rats, anesthesia was induced and
      maintained with halothane in oxygen and air. The MAC was determined by observing
      the response to tail clamping and tested during mild hypoglycemia (blood glucose
      level, 60 mg/dl) and hyperglycemia (blood glucose level, 300 and 500 mg/dl)
      induced by insulin and glucose infusion, respectively (experiment 1). The effects
      of 0.3 and 1.0 mg/kg physostigmine given intraperitoneally on MAC were examined
      in rats with mild and severe hypoglycemia (blood glucose level, 60 and 30 mg/dl;
      experiment 2). RESULTS: In experiment 1, mild hypoglycemia significantly reduced
      the MAC of halothane (0.76 +/- 0.03%) compared with the control value (0.92 +/-
      0.04%), but hyperglycemia did not change MAC. In experiment 2, mild and severe
      hypoglycemia reduced MAC of halothane in a degree-dependent manner. Physostigmine
      (1 mg/kg) had no effect on MAC regardless of blood glucose level, but 0.3 mg/kg
      reduced MAC. CONCLUSIONS: Hypoglycemia reduced anesthetic requirements in a
      degree-dependent manner, whereas hyperglycemia had no effects. Although the
      mechanism of hypoglycemic MAC reduction needs further investigations,
      physostigmine studies suggest that this may not be related to inhibition of
      cholinergic transmission.

PMID- 9286901
TI  - Isoflurane mimics ischemic preconditioning via activation of K(ATP) channels:
      reduction of myocardial infarct size with an acute memory phase.
AB  - BACKGROUND: The authors tested the hypothesis that isoflurane directly
      preconditions myocardium against infarction via activation of K(ATP) channels and
      that the protection afforded by isoflurane is associated with an acute memory
      phase similar to that of ischemic preconditioning. METHODS: Barbiturate
      anesthetized dogs (n = 71) were instrumented for measurement of systemic
      hemodynamics. Myocardial infarct size was assessed by triphenyltetrazolium
      chloride staining. All dogs were subjected to a single prolonged (60 min) left
      anterior descending coronary artery (LAD) occlusion followed by 3 h of
      reperfusion. Ischemic preconditioning was produced by four 5-min LAD occlusions
      interspersed with 5-min periods of reperfusion before the prolonged LAD occlusion
      and reperfusion. The actions of isoflurane to decrease infarct size were examined
      in dogs receiving 1 minimum alveolar concentration (MAC) isoflurane that was
      discontinued 5 min before prolonged LAD occlusion. The interaction between
      isoflurane and ischemic preconditioning on infarct size was evaluated in dogs
      receiving isoflurane before and during preconditioning LAD occlusions and
      reperfusions. To test whether the cardioprotection produced by isoflurane can
      mimic the acute memory of ischemic preconditioning, isoflurane was discontinued
      30 min before prolonged LAD occlusion and reperfusion. The mechanism of
      isoflurane-induced cardioprotection was evaluated in two final groups of dogs
      pretreated with glyburide in the presence or absence of isoflurane. RESULTS:
      Myocardial infarct size was 25.3 +/- 2.9% of the area at risk during control
      conditions. Isoflurane and ischemic preconditioning produced significant (P <
      0.05) and equivalent reductions in infarct size (ischemic preconditioning alone,
      9.6 +/- 2.0; isoflurane alone, 11.8 +/- 2.7; isoflurane and ischemic
      preconditioning, 5.1 +/- 1.9%). Isoflurane-induced reduction of infarct size also
      persisted 30 min after discontinuation of the anesthetic (13.9 +/- 1.5%),
      independent of hemodynamic effects during LAD occlusion. Glyburide alone had no
      effect on infarct size (28.3 +/- 3.9%), but it abolished the protective effects
      of isoflurane (27.1 +/- 4.6%). CONCLUSIONS: Isoflurane directly preconditions
      myocardium against infarction via activation of K(ATP) channels in the absence of
      hemodynamic effects and exhibits acute memory of preconditioning in vivo.

PMID- 9286902
TI  - Neuroprotective effects of dexmedetomidine in the gerbil hippocampus after
      transient global ischemia.
AB  - BACKGROUND: Cerebral ischemia induces a massive release of norepinephrine
      associated with neuronal death in the brain. It has been demonstrated that alpha2
      adrenoceptor agonists decrease the release and turnover of noradrenaline, and
      this might prove advantageous in counteracting the neurodegeneration in ischemic
      brain. Therefore, in the present study, the authors tested whether
      dexmedetomidine, a selective alpha2-receptor agonist, has neuroprotective effects
      in a gerbil transient global ischemia model. METHODS: Ischemia was induced by
      bilateral carotid occlusion for 5 min in diethylether-anesthetized normothermic
      gerbils. Dexmedetomidine was administered subcutaneously in four different
      treatment paradigms (6-8 animals/group): 3 or 30 microg/kg 30 min before and
      thereafter at 3, 12, 24, and 48 h after the occlusion, or 3 or 30 microg/kg at 3,
      12, 24, and 48 h after the occlusion. Control animals were subjected to forebrain
      ischemia but received only saline injections. One week after occlusion, animals
      were transcardially perfused for histochemistry. Neuronal death in the CA1 and
      CA3 regions of the hippocampus and in the hilus of the dentate gyrus was
      evaluated in silver-stained 60-microm coronal sections. RESULTS: Compared with
      saline-treated ischemic animals, dexmedetomidine at a dose of 3 microg/kg given
      before and continued after the induction of ischemia reduced the number of
      damaged neurons in the CA3 area (2 +/- 3 vs. 17 +/- 20 degenerated neurons/mm2; P
      < 0.05). Also in the dentate hilus, the number of damaged neurons was reduced by
      dexmedetomidine (3 microg/kg) given before and continued after ischemia (5 +/- 7
      vs. 56 +/- 42 degenerated neurons/mm2; P < 0.01). CONCLUSIONS: The present data
      demonstrate that dexmedetomidine effectively prevents delayed neuronal death in
      CA3 area and in the dentate hilus in gerbil hippocampus when the management is
      started before the onset of ischemia and continued for 48 h after reperfusion.
      Inhibition of ischemia-induced norepinephrine release may be associated with
      neuroprotection by dexmedetomidine.

PMID- 9286903
TI  - In vitro negative inotropic effect of plasma collected at the time of reperfusion
      in humans undergoing liver transplantation.
AB  - BACKGROUND: During orthotopic liver transplantation (OLT), acute depression of
      myocardial contractility has been suspected at the time of the graft reperfusion.
      METHODS: The authors tested the hypothesis that plasma collected at the time of
      reperfusion in OLT patients exerted a negative inotropic effect on isolated rat
      myocardium. Plasma from 13 OLT patients was collected either before surgical
      incision (group 1, n = 8) or 3-5 min after vena cava and portal vein unclamping
      (group 2, n = 9). Six patients had their pre- and postincision plasma analyzed. A
      postreperfusion syndrome was observed in 3 of 13 patients. Left ventricular rat
      papillary muscles were studied at baseline (T0), 30 min after the addition of
      plasma (T30), and 60 min after the addition of plasma (T60). The authors recorded
      contraction parameters (maximum unloaded shortening velocity [Vmax], peak extent
      of systolic shortening at preload [deltaL], maximum active isometric tension
      [AFi], positive peak tension derivative [+dFi/dt], time-to-peak shortening [TPS],
      and time-to-peak force [TPF]) and relaxation parameters (maximum lengthening
      velocity at preload [VI], negative peak tension derivative [-dFi/dt], index of
      load sensitivity of relaxation [tRi]). RESULTS: In group 1, contraction
      parameters remained unchanged, with the exception of a decreased Vmax at T30 and
      AFi at T60 (each P < 0.05). In group 2, all contraction parameters were
      significantly decreased at T30 and at T60, with the exception of AFi at T60. Both
      types of plasma decreased V1 and altered tRi at T30 and T60, whereas only
      reperfusion plasma decreased -dFi/dt at T30 and T60. At T30, deltaL, -dFi/dt, and
      tRi were significantly more impaired in group 2 than in group 1. There was no
      relationship between inotropic changes and mean arterial pressure decrease at the
      time of reperfusion. CONCLUSION: Plasma collected at the time of graft
      reperfusion in OLT patients exerted negative effects on contraction and
      relaxation performance in isolated rat left ventricular papillary muscle.

PMID- 9286904
TI  - Learning and memory during general anesthesia: an update.

PMID- 9286905
TI  - An introduction to ethics.

PMID- 9286906
TI  - Spinal cord injury as a result of endotracheal intubation in patients with
      undiagnosed cervical spine fractures.

PMID- 9286907
TI  - Perioperative white matter degeneration and death in a patient with a defect in
      mitochondrial oxidative phosphorylation.

PMID- 9286908
TI  - Delayed recovery from muscle weakness due to malignant hyperthermia during
      sevoflurane anesthesia.

PMID- 9286909
TI  - Fatal acute myocardial infarction during general anesthesia in a 7-yr-old boy
      associated with total intramural coronary arteries.

PMID- 9286910
TI  - Fatal pulmonary embolism during liver transplantation.

PMID- 9286911
TI  - Thyroid storm due to functioning metastatic thyroid carcinoma in a burn patient.

PMID- 9286914
TI  - Suction catheter-guided nasotracheal intubation.

PMID- 9286912
TI  - Antinociceptive interaction of intrathecal alpha2-adrenergic agonists, tizanidine
      and clonidine, with lidocaine in rats.
AB  - BACKGROUND: The intrathecal alpha2-adrenergic agonist, clonidine, has been shown
      to have considerable antinociceptive effect, although clonidine causes
      hypotension and bradycardia. The combination of intrathecal clonidine and local
      anesthetics enhances analgesic effects, whereas the combination may cause marked
      hypotension and motor blockade, which may limit the clinical application of the
      combination. Tizanidine, another alpha2-adrenergic agonist, has also provided
      antinociception without producing pronounced hemodynamic changes. This study was
      designed to evaluate the antinociceptive and hemodynamic interactions of
      tizanidine and clonidine with lidocaine. METHODS: Male Sprague Dawley rats were
      chronically implanted with lumbar intrathecal catheters. The tail-flick test was
      used to assess the thermal nociceptive threshold. The ability of intrathecal
      tizanidine, clonidine, lidocaine, or the combinations of alpha2-adrenergic
      agonist and lidocaine to alter the tail-flick latency was examined. To
      characterize the antinociceptive interaction, the isobolographic analysis was
      applied. Additionally, the motor function, blood pressure and heart rate after
      intrathecal administration of drugs and combinations were also monitored.
      RESULTS: Intrathecal tizanidine, clonidine, or the combinations increased the
      tail-flick latency in dose- and time-dependent fashion without affecting motor
      function. The order potencies (dose producing a 50% of peak effect, in microg) of
      tizanidine and clonidine were 1.8 and 0.75, respectively. With isobolographic
      analysis, tizanidine with lidocaine and clonidine with lidocaine showed
      significantly synergistic antinociceptive interaction. Potency ratio analysis and
      fractional analysis also confirmed the synergistic interaction. At the doses in
      the combinations showing comparable antinociception, tizanidine with lidocaine,
      unlike clonidine with lidocaine, did not affect motor function or blood pressure.
      CONCLUSION: The authors' results show that intrathecal tizanidine and clonidine
      synergistically interact with lidocaine so that the degree of antinociception to
      somatic noxious stimuli are enhanced. The antinociceptive synergistic interaction
      between tizanidine and lidocaine may be useful in clinical practice without
      affecting blood pressure, heart rate, or motor function.

PMID- 9286913
TI  - The use of a nasogastric tube as an aid in blind nasotracheal intubation: a
      postscript.

PMID- 9286915
TI  - Formation of a national database on pulmonary hypertension and hepatopulmonary
      syndrome in chronic liver disease.

PMID- 9286916
TI  - A choking hazard during nasal end-tidal CO2 monitoring.

PMID- 9286918
TI  - An unusual capnogram.

PMID- 9286917
TI  - Capsaicin-evoked mechanical allodynia and hyperalgesia cross-nerve territories.

PMID- 9286919
TI  - Relationship between NIH dollars and percentage of residents matched through the
      National Residency Matching Program.

PMID- 9286920
TI  - Perfusion monitoring during radical perineal prostatectomy.

PMID- 9286921
TI  - Perioperative autologous transfusion service: a logical extension of our role in
      the operating room.

PMID- 9286922
TI  - Improving the design of muscle relaxant studies.

PMID- 9286923
TI  - Extubation of the difficult airway.

PMID- 9286924
TI  - Tribute to Dr. Austin Lamont.

PMID- 9286925
TI  - Possible interaction of esmolol and nitrous oxide.

PMID- 9286927
TI  - Long-term angiographic and clinical outcome after percutaneous transluminal
      coronary angioplasty and intracoronary radiation therapy in humans.

PMID- 9286928
TI  - The new portfolio of American Heart Association National Research Awards: initial
      experience.

PMID- 9286929
TI  - Curbing the tobacco menace.

PMID- 9286930
TI  - Regional variations of blood pressure: environment or genes?

PMID- 9286931
TI  - Glucose-insulin-potassium in acute myocardial infarction: the time has come for a
      large, prospective trial.

PMID- 9286932
TI  - Evidence for primary genetic determination of heart rate regulation: chromosomal
      mapping of a genetic locus in the rat.
AB  - BACKGROUND: We investigated whether an accelerated heart rate (HR), observed in
      the stroke-prone spontaneously hypertensive rat (SHRSP(HD)), is a primary,
      genetically determined trait and whether it contributes to blood pressure (BP)
      regulation in this model of polygenic hypertension. METHODS AND RESULTS: We
      measured BP and HR in SHRSP(HD) and normotensive Wistar-Kyoto rats (WKY), as well
      as in F2 hybrids bred from crossing the two strains, at baseline and after 12
      days of dietary NaCl loading. Random marker genome screening and cosegregation
      analysis were performed on F2 hybrids derived from SHRSP(HD)/WKY-0(HD) (n=115)
      and SHRSP(HD)/WKY-1(HD) (n=139) crosses (WKY-0(HD) and WKY-1(HD) are two congenic
      WKY strains). HR in SHRSP(HD) was significantly higher than in WKY-0(HD) both at
      baseline (404+/-30 versus 375+/-46 bpm; P=.0034) and after NaCl (437+/-23 versus
      364+/-40 bpm; P=10(-9)). BP in F2 hybrids showed no significant correlation with
      HR either at baseline or after NaCl loading. HR after NaCl loading but not at
      baseline was significantly linked in a recessive fashion to a locus on chromosome
      3: in animals homozygous for the SHRSP(HD) allele, HR was 414+/-49 compared with
      383+/-44 bpm in heterozygotes and WKY homozygotes (F(210,1)=19.7, P=1.4x10(-5),
      lod score=5.9). The putative BP-relevant gene at this locus, termed HR-SP1,
      showed no evidence of linkage to any of the BP parameters measured. CONCLUSIONS:
      Our results demonstrate that a genetic locus on rat chromosome 3, HR-SP1,
      contributes directly to the regulation of HR in SHRSP(HD) but exhibits no effect
      on BP. Thus, in addition to its modulation by reflex-mediated neurohumoral
      mechanisms, HR is also under the direct influence of primary genetic factors.

PMID- 9286933
TI  - Regional disparities in the incidence of elevated blood pressure among young
      adults: the CARDIA study.
AB  - BACKGROUND: Within the United States, little is known about regional disparities
      in blood pressure (BP), their changes over time, or explanations for their
      existence. METHODS AND RESULTS: A population-based cohort of 5115 black and white
      men and women, 18 to 30 years old in 1985-1986 (balanced on age, race, sex, and
      education), was followed up for 7 years in four centers: Birmingham, Ala;
      Chicago, Ill; Minneapolis, Minn; and Oakland, Calif. Differences in elevated BP
      (EBP) prevalence among centers at years 0, 2, 5, and 7 and in 7-year incidence of
      EBP were assessed. Sociodemographic and dietary variables, physical activity,
      weight, smoking, and alcohol were considered. At year 0, no regional differences
      were seen. Seven years later, there was marked variability in prevalence of EBP
      overall and for both black and white men, from a low in Chicago (9% for black men
      and 5% for white men) to a high in Birmingham (25% for black men and 14% for
      white men). Birmingham also had the highest 7-year incidence (11%) and overall
      prevalence at year 7 (14%). The adjusted odds ratios, with Birmingham as referent
      (95% CIs), for 7-year incidence of EBP overall were 0.38 (0.24, 0.60) for
      Chicago, 0.37 (0.24, 0.57) for Minneapolis, and 0.74 (0.52, 1.07) for Oakland.
      CONCLUSIONS: Regional disparities are absent at baseline but become apparent as
      the cohort ages. These differences are not fully explained by the available
      behavioral and sociodemographic characteristics.

PMID- 9286934
TI  - Short-term economic and health benefits of smoking cessation: myocardial
      infarction and stroke.
AB  - BACKGROUND: Most analyses of the economic benefits of smoking cessation consider
      long-term effects, which are often not of interest to public and private policy
      makers. These analyses fail to account for the time course of the short-run cost
      savings from the rapid decline in risk of acute myocardial infarction (AMI) and
      stroke. METHODS AND RESULTS: We estimate the time course of the fall in risk of
      AMI and stroke after smoking cessation and simulate the impact of a 1% absolute
      reduction in smoking prevalence on the number of and short-term direct medical
      costs associated with the prevented AMIs and strokes. In the first year, there
      would be 924+/-679 (mean+/-SD) fewer hospitalizations for AMI and 538+/-508 for
      stroke, resulting in an immediate savings of $44+/-26 million. A 7-year program
      that reduced smoking prevalence by 1% per year would result in a total of
      63,840+/-15,521 fewer hospitalizations for AMI and 34,261+/-9133 fewer for
      stroke, resulting in a total savings of $3.20+/-0.59 billion in costs, and would
      prevent approximately 13,100 deaths resulting from AMI that occur before people
      reach the hospital. Creating a new nonsmoker reduces anticipated medical costs
      associated with AMI and stroke by $47 in the first year and by $853 during the
      next 7 years (discounting 2.5% per year). CONCLUSIONS: Although primary
      prevention of smoking among teenagers is important, reducing adult smoking pays
      more immediate dividends, both in terms of health improvements and cost savings.

PMID- 9286935
TI  - Association between cigarette smoking and lipid peroxidation in a controlled
      feeding study.
AB  - BACKGROUND: Cigarette smoke may promote atherogenesis by producing oxygen-derived
      free radicals that damage lipids. However, evidence in support of this hypothesis
      is inconsistent because most studies did not control for aspects of diet
      (antioxidants and lipid substrate) that may confound the association between
      smoking and measures of lipid peroxidation. METHODS AND RESULTS: The
      relationships between cigarette smoking and two measures of lipid peroxidation,
      breath ethane (an in vivo assay) and thiobarbituric acid-reactive substances
      (TBARS, an in vitro assay), were examined in 123 adults (11% of whom were
      smokers) participating in a controlled feeding study. After 3 weeks of controlled
      feeding on a common diet (36% total fat, 14% saturated fats, 6% polyunsaturated
      fats, and 12% monounsaturated fats), breath and fasting serum samples were
      collected for measurement of ethane and TBARS, respectively. Baseline
      characteristics of smokers and nonsmokers were similar, including several indices
      related to diet and nutritional status (albumin, cholesterol, body mass index,
      and oxygen radical-absorbing capacity). Cigarette smokers had significantly
      higher breath ethane (8.88 versus 1.71 pmol/L; P<.0001) and TBARS (24.0 versus
      20.7 micromol/mL; P=.008) than nonsmokers. The interval between breath collection
      and the time the last cigarette was smoked was significantly and inversely
      correlated with breath ethane. Neither measure of lipid peroxidation was
      associated with measures of serum cholesterol or albumin, body mass index, or
      serum oxygen radical-absorbing capacity. CONCLUSIONS: Cigarette smokers have
      higher rates of in vivo and in vitro lipid peroxidation. These results support
      the hypothesis that the atherogenic effects of smoking are mediated in part by
      free radical damage to lipids.

PMID- 9286936
TI  - Prospective study of hemostatic factors and incidence of coronary heart disease:
      the Atherosclerosis Risk in Communities (ARIC) Study.
AB  - BACKGROUND: Although hemostatic factors contribute to acute coronary syndromes
      and atherogenesis, few studies have prospectively evaluated the association
      between multiple hemostatic factors and coronary heart disease incidence. METHODS
      AND RESULTS: The Atherosclerosis Risk in Communities Study recruited 14,477
      adults from 45 to 64 years of age who were initially free of coronary heart
      disease. Coronary disease risk factors and several plasma hemostatic factors were
      measured, and incidence of coronary heart disease was ascertained during an
      average follow-up of 5.2 years. Age-, race-, and field center-adjusted relative
      risks of coronary heart disease were significantly elevated (P < or = .05) per
      higher value of fibrinogen (relative risk: men, 1.76; women, 1.54), white blood
      cell count (men, 1.68; women, 2.23), factor VIII coagulant activity (women,
      1.25), and von Willebrand factor antigen (men, 1.20; women, 1.18). Adjustment for
      other risk factors attenuated these associations for fibrinogen (adjusted
      relative risk: men, 1.48; women, 1.21), and it eliminated the white blood cell
      count, factor VIII, and von Willebrand factor associations, consistent with the
      other risk factors either confounding or partly operating through their effects
      on the hemostatic variables. Adjusted standardized relative risks of total
      mortality, ranging from 1.13 to 1.37, were also elevated (P < .05) in relation to
      these four factors. There was no association of coronary disease incidence with
      factor VII, protein C, antithrombin III, or platelet count. CONCLUSIONS: Elevated
      levels of fibrinogen, white blood cell count, factor VIII, and von Willebrand
      factor are risk factors and may play causative roles in coronary heart disease.
      However, their measurement in healthy adults appears to add little to prediction
      of coronary events beyond that of more established risk factors.

PMID- 9286937
TI  - Differential suppression of thromboxane biosynthesis by indobufen and aspirin in
      patients with unstable angina.
AB  - BACKGROUND: We have previously reported aspirin failure in suppressing enhanced
      thromboxane (TX) biosynthesis in a subset of episodes of platelet activation
      during the acute phase of unstable angina. The recent discovery of a second
      prostaglandin H synthase (PGHS-2), inducible in response to inflammatory or
      mitogenic stimuli, prompted us to reexamine TXA2 biosynthesis in unstable angina
      as modified by two cyclooxygenase inhibitors differentially affecting PGHS-2
      despite a comparable impact on platelet PGHS-1. METHODS AND RESULTS: We
      randomized 20 patients (15 men and 5 women aged 59+/-10 years) with unstable
      angina to short-term treatment with aspirin (320 mg/d) or indobufen (200 mg BID)
      and collected 6 to 18 consecutive urine samples. Urinary 11-dehydro-TXB2 was
      extracted and measured by a previously validated radioimmunoassay as a reflection
      of in vivo TXA2 biosynthesis. Metabolite excretion averaged 102 pg/mg creatinine
      (median value; n=76) in the aspirin group and 55 pg/mg creatinine (median value;
      n=99) in the indobufen group (P<.001). There were 16 samples (21%) with 11
      dehydro-TXB2 excretion >200 pg/mg creatinine among patients treated with aspirin
      versus 6 such samples (6%) among those treated with indobufen (P<.001). In vitro
      and ex vivo studies in healthy subjects demonstrated the capacity of indobufen to
      largely suppress monocyte PGHS-2 activity at therapeutic plasma concentrations.
      In contrast, aspirin could only inhibit monocyte PGHS-2 transiently at very high
      concentrations. CONCLUSIONS: We conclude that in unstable angina, episodes of
      aspirin-insensitive TXA2 biosynthesis may reflect extraplatelet sources, possibly
      expressing the inducible PGHS in response to a local inflammatory milieu, and a
      selective PGHS-2 inhibitor would be an ideal tool to test the clinical relevance
      of this novel pathway of arachidonic acid metabolism in this setting.

PMID- 9286938
TI  - Sustained platelet glycoprotein IIb/IIIa blockade with oral xemilofiban in 170
      patients after coronary stent deployment.
AB  - BACKGROUND: Inhibition of platelet aggregation with parenteral glycoprotein (GP)
      IIb/IIIa receptor blockers can reduce the ischemic complications of angioplasty.
      Sustained efficacy and safety of protracted GP IIb/IIIa blockade with an orally
      administered agent have not previously been determined. This study is the first
      randomized, dose-ranging, single-blind, placebo-controlled trial of xemilofiban,
      an oral platelet GP IIb/IIIa receptor antagonist, administered to patients after
      intracoronary stent deployment. The pharmacodynamic efficacy of xemilofiban
      induced platelet inhibition and clinical safety of this agent was evaluated
      during chronic therapy. METHODS AND RESULTS: After elective intracoronary stent
      deployment, patients were randomized to receive placebo (250 mg ticlopidine P.O.
      BID) or xemilofiban in doses of 5, 10, 15, or 20 mg P.O. BID. All patients
      received 325 mg aspirin P.O. QD. Inhibition of ex vivo platelet aggregation in
      response to 20 micromol/L ADP and 4 microg/mL collagen was measured over time
      after the initial dose of study drug and at 1 and 2 weeks of chronic therapy.
      Study drug was discontinued after 2 weeks, and all patients were followed
      clinically for > or = 30 days. Oral xemilofiban resulted in a dose-dependent
      inhibition of platelet aggregation in response to both agonists that was
      sustained through 2 weeks of chronic therapy. Doses of xemilofiban required to
      achieve > or = 50% inhibition of platelet aggregation were > or = 10 mg, and the
      duration of inhibition was 8 to 10 hours. No significant hemorrhagic episodes or
      blood transfusions were observed in this trial. CONCLUSIONS: Oral xemilofiban in
      doses of > or = 10 mg produced > or = 50% inhibition of platelet aggregation in
      response to ADP and collagen for 8 to 10 hours after dosing. Platelet inhibition
      was sustained through 2 weeks of chronic therapy. The optimal duration of oral GP
      IIb/IIIa blockade to effectively suppress recurrent ischemic events after
      coronary intervention remains to be determined.

PMID- 9286939
TI  - Electron beam computed tomographic coronary calcium as a predictor of coronary
      events: comparison of two protocols.
AB  - BACKGROUND: We assessed the accuracy of two electron beam computed tomography
      (EBCT) protocols for predicting coronary events. METHODS AND RESULTS: In 1994, 24
      months after enrollment in a longitudinal study, 326 high-risk adults underwent
      both 3- and 6-mm image-slice thickness EBCT scanning and were followed up for
      32.0+/-4.0 additional months. Events were defined as either coronary death,
      myocardial infarction, or revascularization. We monitored these subjects for the
      32-month postscanning period with yearly phone calls and acquisition of records
      for all hospital admissions. At the time of scanning, 11 subjects (3%) had
      already suffered 12 events (5 infarctions and 7 revascularizations) during the 24
      month prescanning period. During the postscanning period, 18 subjects (6%)
      suffered 23 events (5 coronary deaths, 6 infarctions, and 12 revascularizations).
      Thus, 28 subjects (9%) suffered 35 events. Calcium quantities calculated for both
      protocols, performed on the same subjects, were sorted in ascending order and
      divided into equal quartiles. When revascularizations were included, there was a
      significant trend toward higher frequencies of events with increasing calcium
      quantity (P<.01). However, coronary death and infarction were not significantly
      more frequent in higher quartiles. These relationships were preserved in the
      subjects without prior events at the time of scanning. CONCLUSIONS: Calcium
      quantities from the 3-mm and the more reproducible 6-mm scanning are equally
      accurate for predicting events. Coronary calcium amount appears to be a weak
      predictor of coronary death and infarction. Its predictive accuracy is superior
      for predicting revascularization.

PMID- 9286940
TI  - Profound and sustained inhibition of platelet aggregation by Fradafiban, a
      nonpeptide platelet glycoprotein IIb/IIIa antagonist, and its orally active
      prodrug, Lefradafiban, in men.
AB  - BACKGROUND: Clinical trials have demonstrated that platelet glycoprotein (GP)
      IIb/IIIa antagonists effectively prevent acute thrombotic events. Orally active
      GP IIb/IIIa antagonists are essential to evaluate the clinical benefit of long
      term treatment. We therefore investigated platelet inhibition by the GP IIb/IIIa
      antagonist Fradafiban (BIBU 52; Fradafiban is the recommended INN of BIBU 52) and
      its orally administered prodrug, Lefradafiban (BIBU 104; Lefradafiban is the
      recommended INN of BIBU 104) in healthy subjects. METHODS AND RESULTS: The
      activity and plasma levels of Fradafiban and Lefradafiban were evaluated in
      double-blind, placebo-controlled studies in 130 healthy male subjects. One to 15
      mg Fradafiban continuously infused over 30 minutes reversibly inhibited platelet
      aggregation in platelet-rich plasma ex vivo in response to 20 micromol/L ADP (5
      mg, 100% inhibition at 27 minutes after administration) and to both 1.0 (5 mg,
      100%) and 10 microg/mL (15 mg, 97+/-3%) collagen. Single oral doses of
      Lefradafiban inhibited ADP-induced aggregation by 59+/-14% (50 mg [mean+/-SD];
      n=8), 90+/-12% (100 mg), and 99+/-2% (150 mg) 8 hours after administration.
      Correlations between activity and Fradafiban plasma levels were identical after
      Fradafiban and Lefradafiban treatment. After day 1, oral TID Lefradafiban
      treatment for 7 days inhibited aggregation by > or = 31+/-9.6% (25 mg TID; n=8),
      53+/-12% (50 mg; n=7), and 88+/-6.6% (75 mg; n=8) just before the next dose. A
      similar correlation between the activity and Fradafiban plasma levels was
      observed at days 1, 2, and 7. CONCLUSIONS: Oral administration of Lefradafiban
      maintains the potent platelet GP IIb/IIIa antagonism of Fradafiban during
      treatment of healthy subjects for 1 week without signs of loss of the
      antiplatelet activity.

PMID- 9286941
TI  - Incidence, clinical characteristics, and prognostic significance of right bundle
      branch block in acute myocardial infarction: a study in the thrombolytic era.
AB  - BACKGROUND: Whereas the significance of right bundle-branch block (RBBB) in acute
      myocardial infarction was extensively studied in the prethrombolytic era, a
      possible change in the overall incidence and meaning of RBBB as a consequence of
      thrombolytic therapy is not well known. METHODS AND RESULTS: A multicenter,
      prospective study of 1238 patients consecutively diagnosed with acute myocardial
      infarction and admitted to three coronary care units was conducted. ECGs during
      the acute phase and clinical events until discharge and 1-year follow-up were
      monitored. In the 135 (10.9%) patients in whom RBBB was found, there were 51
      (37.8%) new cases, 46 (34.1%) old cases, and 38 (28.1%) cases with an
      indeterminate time of origin. New RBBB was permanent in 26 and transient in 25
      patients. RBBB was isolated in 76 (56%) and bifascicular in the remaining 59
      (44%) patients. The following complications were more frequently associated with
      RBBB than non-RBBB patients: heart failure, 24% versus 46% (P<.001); use of
      pacemaker because of atrioventricular block, 3.6% versus 11% (P<.001); and 1-year
      mortality, 17.6% versus 40.7% (P<.001). Early mortality was significantly higher
      for new RBBB (43.1%, P<.001) than for old (15.5%) and indeterminate (15.3%) RBBB.
      These figures for 1-year mortality were 58.8% (P<.001), 35.5 (P<.01), and 23%
      (NS), respectively. Permanent and transient RBBB had different mortality rates:
      early mortality, 76% versus 8%, and 1-year mortality, 84% versus 32% (P<.001 for
      both). For isolated RBBB versus bifascicular block, early mortality was 14.4%
      versus 40.6%, and 1-year mortality was 30.2% versus 54.2% (P<.05 for both).
      Multivariate analysis showed an independent prognostic value of RBBB for early
      and 1-year mortality. CONCLUSIONS: The overall meaning of RBBB in acute
      myocardial infarction has not changed in the thrombolytic era, although a higher
      rate of new and transient RBBB and a lower rate of bifascicular block may
      represent a beneficial effect of thrombolytic therapy.

PMID- 9286942
TI  - Evidence of multifocal activity of coronary disease in patients with acute
      myocardial infarction.
AB  - BACKGROUND: Destabilization of the fibrous cap facilitates plaque rupture,
      thrombus formation, and myocardial infarction. Because systemic stimuli, such as
      lipoproteins, infectious agents, and autoantigens, may incite this reaction, one
      may wonder whether disruption mechanisms are only local or systemic and
      infarction is caused by an arbitrary plaque event or by a systemic, acute
      activity of the coronary disease. METHODS AND RESULTS: Early (3 to 5 days) and
      late (1 month) peri-infarction coronary angiographic data in 23 patients with
      first infarction were compared with that in 23 similar patients, with angiography
      performed because of stable angina and repeated after 1 month before angioplasty.
      Nonculprit lesion changes at the narrowest point defined progression or
      regression when exceeding 0.27 mm. In patients with recent infarction we found
      that 16 had progression, 4 had regression, 1 had both, 2 were steady (values in
      patients with stable angina being 2 [P<.0011, 1 [NS], 0 [NS], and 20 [P<.001]);
      27 lesions were infarct related; 17 of the 45 nonculprit lesions progressed and 5
      regressed (values in stable angina being 2 [P<.001] and 1 [P<.05] out of 78);
      minimal diameter reduction of progressing stenoses averaged 0.39 mm; lumen
      increase of regressing lesions averaged 0.30 mm; 3 patients developed interim
      rest angina associated with progression of a nonculprit lesion. CONCLUSIONS: A
      greater proportion of subjects and lesions with progression or regression (in
      infarction versus stable angina) supports the hypothesis that infarction is a
      hallmark of systemic coronary disease activity. Changes might vary according to
      the "maturation" stage of an atheroma, and maximal expression would be at the
      level of the offending plaque. Shrinkage, thrombolysis, or vascular remodeling
      would determine the residual plaque morphology.

PMID- 9286943
TI  - Glucose-insulin-potassium therapy for treatment of acute myocardial infarction:
      an overview of randomized placebo-controlled trials.
AB  - BACKGROUND: Glucose-insulin-potassium (GIK) therapy has been advocated for the
      treatment of acute myocardial infarction. However, the results from the clinical
      trials have been inconclusive, largely because of the small number of patients
      recruited and discrepancies between protocols used in these studies. METHOD AND
      RESULTS: A systematic MEDLINE search for all the randomized placebo-controlled
      studies of GIK therapy in acute myocardial infarction was made, and a meta
      analysis of the mortality data was performed. Fifteen trials were identified, 5
      were excluded because of poor randomization, and 1 was excluded because
      recruitment was limited to diabetic patients. The 9 remaining trials with a total
      of 1932 patients were included in the analysis. Hospital mortality was reduced
      from 21% (205 of 972 patients) in the placebo group to 16.1% (154 of 956) in the
      GIK group (P=.004; odds ratio, 0.72; 95% confidence interval [CI], 0.57 to 0.90).
      The proportional mortality reduction was 28% (CI, 10% to 43%). The number of
      lives saved per 1000 patients treated was 49 (95% CI, 14 to 83). CONCLUSIONS: The
      findings indicate that GIK therapy may have an important role in reducing the in
      hospital mortality after acute myocardial infarction. The value of this therapy
      in the era of thrombolysis and acute revascularization by primary angioplasty can
      be fully resolved only by conducting a large randomized mortality study.

PMID- 9286944
TI  - Lossy (15:1) JPEG compression of digital coronary angiograms does not limit
      detection of subtle morphological features.
AB  - BACKGROUND: Development of the "all-digital" cardiac catheterization laboratory
      has been slowed by substantial computer archival and transfer requirements. Lossy
      data compression reduces this burden but creates irreversible changes in images,
      potentially impairing detection of clinically important angiographic features.
      METHODS AND RESULTS: Fifty image sequences from 31 interventional procedures were
      viewed both in the original (uncompressed) state and after 15:1 lossy Joint
      Photographic Expert's Group (JPEG) compression. Experienced angiographers
      identified dissections, suspected thrombi, and coronary stents, and their results
      were compared with those from a consensus panel that served as a "gold standard."
      The panel and the individual observers reviewed the same image sequences 4 months
      after the first session to determine intraobserver variability. Intraobserver
      agreement for original images was not significantly different from that for
      compressed images (89.8% versus 89.5% for 600 pairs of observations in each
      group). Agreement of individual observers with the consensus panel was not
      significantly different for original images from that for compressed images
      (87.6% versus 87.3%; CIs for the difference, -4.0%, 4.0%). Subgroup analysis for
      each observer and for each detection task (dissection, suspected thrombus, and
      stent) revealed no significant difference in agreement. CONCLUSIONS: The
      identification of dissections, thrombi, and coronary stents is not substantially
      impaired by the application of 15:1 lossy JPEG compression to digital coronary
      angiograms. These data suggest that digital angiographic images compressed in
      this manner are acceptable for clinical decision-making.

PMID- 9286945
TI  - Sustained hemodynamic efficacy of therapy tailored to reduce filling pressures in
      survivors with advanced heart failure.
AB  - BACKGROUND: During therapy to relieve congestion in advanced heart failure,
      cardiac filling pressures can frequently be reduced to near-normal levels with
      improved cardiac output. It is not known whether the early hemodynamic
      improvement and drug response can be maintained long term. METHODS AND RESULTS:
      After referral for cardiac transplantation with initially severe hemodynamic
      decompensation, 25 patients survived without transplantation to undergo
      hemodynamic reassessment after 8+/-6 months of treatment tailored to early
      hemodynamic response. Initial changes included net diuresis, increased ACE
      inhibitor doses, and frequent addition of nitrates. After 8 months of therapy,
      early reductions were sustained for pulmonary wedge pressure (24+/-9 to 15+/-5 mm
      Hg early; 12+/-6 mm Hg late) and systemic vascular resistance (1651+/-369 to
      1207+/-281 dynes x s(-1) x cm(-5) early; 1003+/-193 dynes x s(-1) x cm(-5) late).
      Acute response to doses persisted at reevaluation. Sustained reduction in filling
      pressures was accompanied by a progressive increase in stroke volume (42+/-10 to
      56+/-13 mL early; 79+/-20 mL late), improved functional class, and freedom from
      resting symptoms. Study design did not control for amiodarone, which was
      initiated for arrhythmias in 12 patients and associated with greater improvement
      in cardiac index (1.8 to 3.2 L min(-1) x m(-2) late on amiodarone versus 2.0 to
      2.6 L x min(-1) x m(-2), P<.05). CONCLUSIONS: During chronic therapy tailored to
      early hemodynamic response in advanced heart failure, acute vasodilator response
      persists, and near-normal filling pressures can be maintained in patients who
      survive without transplantation. Stroke volumes at low filling pressures increase
      further over time. Chronic hemodynamic improvement was accompanied by symptomatic
      improvement, but the contributions of the monitored hemodynamic approach,
      increased vasodilator doses, and comprehensive outpatient management have not yet
      been established.

PMID- 9286946
TI  - Effects of chronic ACE inhibition on sympathetic nerve traffic and baroreflex
      control of circulation in heart failure.
AB  - BACKGROUND: In congestive heart failure ACE inhibitors chronically reduce plasma
      norepinephrine. No information exists, however, on whether and to what extent
      this reduction reflects a true chronic inhibition of sympathetic outflow and
      which mechanisms may be responsible. METHODS AND RESULTS: In 24 patients aged
      60.3+/-2.0 years (mean+/-SEM) affected by congestive heart failure (New York
      Heart Association class II) and treated with diuretics and digitalis, we measured
      mean arterial pressure (Finapres), plasma renin activity and angiotensin II
      levels (radioimmunoassay), plasma norepinephrine (high-performance liquid
      chromatography), and muscle sympathetic nerve activity (microneurography at a
      peroneal nerve) at rest and during baroreceptor stimulation and deactivation
      caused by stepwise intravenous infusions of phenylephrine and nitroprusside,
      respectively. In 12 patients measurements were repeated after a 2-month addition
      of the ACE inhibitor benazepril (10 mg/d P.O.), while in the remaining 12
      patients they were performed again after 2 months without any treatment
      modifications. Benazepril did not alter mean arterial pressure, markedly
      increased plasma renin activity, reduced plasma angiotensin II, and caused a
      nonsignificant reduction in plasma norepinephrine. In contrast, muscle
      sympathetic nerve traffic was significantly reduced (-30.5+/-5.3%, P<.01). This
      reduction was accompanied by no change in the sympathoexcitatory responses to
      baroreceptor deactivation but by a marked enhancement of the sympathoinhibitory
      responses to baroreceptor stimulation (103.5+/-3.4%). CONCLUSIONS: These results
      provide the first direct evidence that in congestive heart failure chronic ACE
      inhibitor treatment is accompanied by a marked reduction in central sympathetic
      outflow. This reduction may depend on a persistent restoration of baroreflex
      restraint on the sympathetic neural drive.

PMID- 9286947
TI  - Histological substrate of atrial biopsies in patients with lone atrial
      fibrillation.
AB  - BACKGROUND: Lone atrial fibrillation (LAF) is a common clinical syndrome, but its
      origin remains unknown. METHODS AND RESULTS: We performed endomyocardial biopsies
      of the right atrial septum (2 to 3 per patient; mean, 2.8) and of the two
      ventricles (6 per patient) in 12 patients (10 men, 2 women; mean age, 32 years)
      with paroxysmal LAF refractory to conventional antiarrhythmic treatment. As
      controls, we used endomyocardial biopsies (3 to 5 per patient; mean, 4.4) from
      the right atrial septum of 11 patients with Wolff-Parkinson-White syndrome (WPW)
      undergoing resection of the abnormal AV pathway. The weight of the biopsies
      ranged from 2.8 to 4.5 mg. Biopsy samples were processed for histology and
      electron microscopy and were read by a pathologist blinded to clinical data. All
      patients underwent two-dimensional Doppler echocardiography; cardiac
      catheterization; coronary angiography; and hormonal, virologic, and
      electrophysiological studies. All tests and WPW biopsies were normal, but all LAF
      atrial biopsy specimens (average, 2.8 per patient) showed abnormalities
      (P<.0001). The type of abnormalities varied: Two patients had a severe
      hypertrophy with vacuolar degeneration of the atrial myocytes and ultrastructural
      evidence of fibrillolysis occupying >50% of the areas assessed morphometrically
      (P=.50), 8 had lymphomononuclear infiltrates with necrosis of the adjacent
      myocytes (5 with fibrosis and 3 without; P<.003), and 2 had only nonspecific
      patchy fibrosis (P=.50). Biventricular biopsies were abnormal in only 3 patients
      and showed inflammatory infiltrates similar to those found in atrial biopsies.
      CONCLUSIONS: Abnormal atrial histology was uniformly found in multiple biopsy
      specimens in all patients with LAF. It was compatible with a diagnosis of
      myocarditis in 66% of patients (active in 25%) and of noninflammatory localized
      cardiomyopathy in 17% and was represented by patchy fibrosis in 17%. The cause of
      the pathological changes, which were found only in atrial septal biopsies but not
      in biventricular biopsies, in 75% of patients remains unknown.

PMID- 9286948
TI  - Do high proinsulin and C-peptide levels play a role in autonomic nervous
      dysfunction?: Power spectral analysis in patients with non-insulin-dependent
      diabetes and nondiabetic subjects.
AB  - BACKGROUND: Immunoreactive insulin has been shown to predict the development of
      parasympathetic autonomic neuropathy. It is possible that constituents of
      immunoreactive insulin could explain this association. In this cross-sectional
      study, the relationship of specific insulin, C-peptide, and proinsulin with
      autonomic nervous dysfunction was evaluated in 57 NIDDM patients and 108 control
      subjects. METHODS AND RESULTS: The frequency-domain analysis of heart rate
      variability was determined by using spectral analysis from stationary regions of
      registrations while the subjects breathed spontaneously in a supine position.
      Total power was divided into three frequency bands: low (0 to 0.07 Hz), medium
      (MFP, 0.07 to 0.15 Hz), and high (HFP, 0.15 Hz to 0.50 multiplied by the
      frequency equal to the mean RR interval). In NIDDM patients, total power, the
      three frequency bands (P<.001 for each), and the MFP/HFP ratio (P=.016), which
      expresses sympathovagal balance, were reduced compared with control subjects.
      Fasting proinsulin (r(s)=-.324, P=.014 for diabetics and r(s)=-.286, P=.003 for
      control subjects), C-peptide (r(s)=-.492, P<.001 for diabetics and r(s)=-.304,
      P=.001 for control subjects), and total immunoreactive insulin (r(s)=-.291,
      P=.028 for diabetics and r(s)=-.228, P=.017 for control subjects) were inversely
      related to MFP/HFP. For proinsulin and C-peptide the results did not change after
      controlling for the effects of age, body mass index, and fasting glucose.
      CONCLUSIONS: Both proinsulin and C-peptide levels were significantly associated
      with the sympathovagal balance of autonomic nervous function in NIDDM patients
      and control subjects, but this study cannot determine whether these compounds are
      directly involved in autonomic nervous dysfunction.

PMID- 9286949
TI  - Adenosine-sensitive ventricular tachycardia: right ventricular abnormalities
      delineated by magnetic resonance imaging.
AB  - BACKGROUND: Adenosine-sensitive ventricular tachycardia (VT) is thought to be due
      to cAMP-mediated triggered activity. It typically originates from the RVOT and
      occurs in patients with apparently normal hearts. Using magnetic resonance
      imaging (MRI), we tested the hypothesis that adenosine-sensitive VT occurs in
      patients without structural heart disease. METHODS AND RESULTS: Fourteen patients
      (9 women; age, 47+/-19 years) presented with sustained VT (n=3), repetitive
      monomorphic VT (n=7), or both (n=4). VT terminated with adenosine in each patient
      and was sensitive to vagal maneuvers in 9 of 11 and verapamil in 10 of 12. VT
      originated from the right ventricular outflow tract in 10 patients, the right
      ventricular apex in 1, and the left ventricular septum in 3. Conventional studies
      included normal signal-averaged ECGs in 9 of 9, normal right ventricular
      echocardiography in 10 of 10, and normal left ventriculography and coronary
      angiography in 6 of 7. In contrast, MRI scans were abnormal in 10 of 14 patients.
      These abnormalities included focal thinning (6), fatty infiltration (4), and wall
      motion abnormalities (4) of the right ventricle. The most common site of MRI
      abnormalities was the right ventricular free wall, but there was a poor
      correlation between the site of MRI abnormalities and the origin of VT. Among 18
      control patients without clinical heart disease, thinning of the right
      ventricular wall was noted in only 1 patient (patients versus control subjects,
      P=.0001). CONCLUSIONS: Patients with idiopathic adenosine-sensitive VT comprise a
      heterogeneous group as assessed by MRI, with 70% demonstrating mild structural
      abnormalities. However, it is unlikely that these findings are causally related
      to tachycardia, and the functional significance of these anatomic abnormalities
      is uncertain.

PMID- 9286950
TI  - Can adenosine 5'-triphosphate be used to select treatment in severe vasovagal
      syndrome?
AB  - BACKGROUND: Selection of treatment in vasovagal syndrome should be guided by the
      mechanism of symptoms. This study determined whether a simple drug test may
      assess one mechanism. METHODS AND RESULTS: To identify patients at risk of severe
      cardioinhibitory response of vagal origin, we infused 20 mg ATP into 316 patients
      hospitalized for recurrent syncope (n=195) or presyncope (n=121) of unknown
      origin and into normal subjects (n=51). We then assessed the ECG and clinical
      responses to the drug, recommended therapy, and followed up the subjects
      chronically. A cardiac pause > 10 seconds was seen in only 3 normal subjects
      (6%). Therefore, a pause < or = 10 seconds yielded the approximately 95th
      percentile of the normal range. ATP provoked a pause > 10 seconds in 130
      symptomatic patients (41%) and a pause < or = 10 seconds in 186 symptomatic
      patients (59%). Thus, symptomatic patients with pauses > 10 seconds were proposed
      for pacemaker implantation; all other patients and normal subjects were simply
      monitored. Among long-pause patients with follow-up, the observed recurrence rate
      for the 104 with pacemakers was one-third that for the 21 who were only monitored
      (P<.0001). Among followed-up short-pause patients, the rate in the 153 monitored
      only patients did not differ from the 20 implanted patients (P=.432).
      CONCLUSIONS: The vagal effect of ATP may identify the subgroup of patients at
      high risk of severe cardioinhibitory response of vagal origin who likely will
      benefit from pacemaker therapy. This fast, uncomplicated test should be
      considered for further use in screening patients with vasovagal syndrome.

PMID- 9286951
TI  - Heart rate variability in patients with atrial fibrillation is related to vagal
      tone.
AB  - BACKGROUND: Analysis of heart rate variability (HRV) has thus far not been
      applied in patients with atrial fibrillation, probably because of the presumed
      absence of any form of patterning of the ventricular rhythm, particularly vagally
      mediated respiratory arrhythmia. However, such patterning is theoretically
      conceivable given the function of the atrioventricular node in atrial
      fibrillation and its susceptibility to autonomic influences. METHODS AND RESULTS:
      Sixteen patients (mean age, 56+/-4 years) with long-term atrial fibrillation on
      fixed doses of digoxin or verapamil were studied; 12 healthy men in sinus rhythm
      were used as control subjects. HRV (standard deviation of RR intervals [SD],
      coefficient of variance [CV], the root-mean-square of successive difference
      [RMSSD], and low-frequency [LF] and high-frequency power [HF]) was analyzed
      during 500 RR intervals at baseline, after administration of propranolol (0.2
      mg/kg I.V.), and after subsequent administration of methylatropine (0.02 mg/kg
      I.V.). HRV at baseline and changes in HRV after methylatropine were then related
      to vagal tone (vagal cardiac control), quantified as the decrease in mean RR
      after methylatropine. Baseline HRV was higher in the atrial fibrillation group
      than in the control group; after propranolol, HRV increased in both groups; after
      methylatropine, HRV neared zero in the control group, whereas it returned to
      baseline values in the atrial fibrillation group. SD, RMSSD, LF, and HF at
      baseline were significantly (P<.05) correlated with vagal tone in the control
      group but also in the atrial fibrillation group (correlation coefficients of .60,
      .61, .57, and .64, respectively). Even stronger correlations were observed
      between changes in these parameters after methylatropine and vagal tone,
      particularly in the atrial fibrillation group (correlation coefficients of .89,
      .87, .72, and .90, respectively). CONCLUSIONS: This study shows that HRV in
      patients with atrial fibrillation is related to vagal tone.

PMID- 9286952
TI  - Probability of successful defibrillation at multiples of the defibrillation
      energy requirement in patients with an implantable defibrillator.
AB  - BACKGROUND: The probability of successful defibrillation has been determined in
      normal animals but not in patients undergoing defibrillator implantation.
      Therefore, the purpose of this prospective study was to determine the probability
      of successful defibrillation in humans on the basis of a step-down defibrillation
      energy requirement. METHODS AND RESULTS: Fifty-three consecutive patients
      underwent five separate inductions of ventricular fibrillation after the
      defibrillation energy requirement was determined with the use of small decrements
      and a step-down protocol (20, 15, 12, 10, 8, 6, 5, 4, 3, 2, 1, and 0.8 J). The
      first shock energy for defibrillation was either 1.0, 1.3, 1.5, 1.7, or 2.0 times
      the defibrillation energy requirement, and the likelihoods of successful
      defibrillation were 70+/-27%, 84+/-12%, 86+/-25%, 80+/-29%, and 88+/-32%,
      respectively (P=.03). The frequencies of uniformly successful defibrillation (5
      of 5 defibrillation attempts) were 30%, 27%, 60%, 64%, and 73%, respectively
      (P=.01). Seven patients in whom the defibrillation energy requirement was <4 J
      had an overall rate of successful defibrillation of 54+/-20% compared with 86+/
      20% in the remaining 47 patients (P=.002). The likelihood of successful
      defibrillation at twice the defibrillation energy requirement was 98% in the 46
      patients with a defibrillation energy requirement of >4 J and 67% in the 7
      patients with a defibrillation energy requirement of <4 J (P=.17). An absolute
      safety margin of 7 J was associated with a 96% probability of successful
      defibrillation. CONCLUSIONS: The probability of successful defibrillation is 70%
      at the defibrillation energy requirement. The probability plateaus at 88%, at
      twice the defibrillation energy requirement. A 96% probability of successful
      defibrillation is achieved at an absolute safety margin of 7 J, and a 98% success
      rate is achieved at energies that are twice the defibrillation energy requirement
      if the defibrillation energy requirement is >4 J. If the defibrillation energy
      requirement is <4 J, larger multiples of the defibrillation energy requirement
      are needed to achieve a high probability of successful defibrillation.

PMID- 9286953
TI  - Effect of high-altitude exposure in the elderly: the Tenth Mountain Division
      study.
AB  - BACKGROUND: More than 5 million people/year over age 60 visit high altitude,
      which may exacerbate underlying cardiac or pulmonary disease. We hypothesized
      that the elderly would exhibit an impaired functional capacity at altitude, with
      increased myocardial ischemia compared with sea level (SL). METHODS AND RESULTS:
      Twenty veterans (68+/-3 years) were studied at (1) SL, (2) acute simulated
      altitude to 2500 m, and (3) after 5 days of acclimatization to 2500 m. With acute
      altitude, PaO2 and oxyhemoglobin saturation decreased and pulmonary artery
      pressure increased 43%, associated with sympathetic activation. VO2peak decreased
      12% acutely but normalized after acclimatization. The best predictor of VO2peak
      with acute altitude was VO2peak at SL (r=.94). The double product that induced 1
      mm ST depression during exercise with acute altitude was 5% less than SL but
      normalized after acclimatization. One patient with severe coronary disease
      sustained a myocardial infarction after an exercise test. CONCLUSIONS: Moderate
      altitude exposure in the elderly is associated with hypoxemia, sympathetic
      activation, and pulmonary hypertension resulting in a reduced exercise capacity
      that is predictable based on exercise performance at SL. Patients with coronary
      artery disease who are well compensated at SL do well at moderate altitude,
      although acutely ischemia may be provoked at modestly lower myocardial and
      systemic work rates. The elderly acclimatize well with normalization of SL
      performance after 5 days. A prudent policy would be for elderly individuals,
      particularly those with coronary artery disease, to limit their activity during
      the first few days at altitude to allow this acclimatization process to occur.

PMID- 9286954
TI  - Anatomic features and surgical strategies in double-outlet right ventricle.
AB  - BACKGROUND: The objective of this study was to review anatomic features and
      surgical strategies in children with double-outlet right ventricle (DORV) and to
      assess risk factors for early mortality. METHODS AND RESULTS: Records were
      reviewed of all children with DORV undergoing surgery between 1978 and 1993.
      Noncomplex patients (group 1) had atrioventricular (AV) concordance, a single
      ventricular septal defect (VSD), balanced ventricles, no straddling AV valves,
      and no major pulmonary artery anomaly. Group 2 (complex) comprised all remaining
      patients. Independent risk factors analyzed included location of the main VSD,
      presence of additional VSDs, coarctation, ventricular outflow obstruction,
      ventricular hypoplasia, age at operation, operation before 1985, previous
      palliation, and type of definitive operation. Of 193 patients, 117 were in group
      1 and 76 in group 2. In 148 patients, biventricular repair was undertaken,
      including 111 of 117 group 1 patients and 37 of 76 group 2 patients. Early
      mortality was higher among group 2 patients undergoing biventricular repair than
      among group 1 patients (8 of 37 versus 4 of 111, P<.005) and higher than group 2
      patients undergoing a Fontan procedure (none of 29, P<.01). Aortic arch
      obstruction, operation before 1985, and multiple VSDs were significant risk
      factors for mortality. Age <1 month (P<.05) and multiple VSDs (P<.005) were
      independent risk factors after definitive repair. Up-to-date follow-up is
      available on 144 surviving patients, with 127 (88%) in New York Heart Association
      class I and the remaining 17 in class II. Overall 10-year survival probability
      was 81%, whereas probability of survival, free from reoperation (after definitive
      surgery), was 65% at 10 years. CONCLUSIONS: Biventricular repair can be achieved
      in most patients with DORV with low risk. In complex DORV, a Fontan procedure is
      associated with a lower surgical mortality.

PMID- 9286955
TI  - Expression and localization of platelet-derived growth factor ligand and receptor
      protein during acute and chronic rejection of rat cardiac allografts.
AB  - BACKGROUND: The molecular mechanisms of cardiac allograft vasculopathy (CAV)
      remain largely unknown. Using rat cardiac allografts, we examined by
      immunohistochemistry the expression and localization of platelet-derived growth
      factor ligand (PDGF-AA and -BB) and receptor (R alpha and R beta) proteins during
      acute and chronic rejection. METHODS AND RESULTS: In acute rejection, a prominent
      induction of both PDGF ligand and receptor proteins occurred in the interstitial
      mononuclear inflammatory cells (P<.05), most of which were ED1-immunoreactive.
      PDGF-R beta was also induced in the capillary endothelium (P<.01). In cardiac
      allografts with severe intimal thickening, PDGF-AA expression was localized to
      the media and intima, whereas PDGF-BB expression was less prominent and was
      detected mainly in interstitial ED1-immunoreactive inflammatory cells. Double
      staining revealed that intimal cells expressing PDGF-AA were alpha-smooth muscle
      actin-positive but also alpha-smooth muscle actin-negative myofibroblast-like
      cells and to a lesser extent, ED1-immunoreactive cells. Both PDGF-R alpha and -R
      beta expression occurred in intimal, arterial endothelial, and interstitial
      mononuclear inflammatory cells. High-dose cyclosporin A (CsA) treatment
      significantly reduced both PDGF-AA and PDGF-R alpha expression in intimal cells.
      Furthermore, linear regression analysis revealed that PDGF-AA, PDGF-R alpha, and
      PDGF-R beta expression in intimal cells and PDGF-BB expression in interstitial
      mononuclear inflammatory cells correlated with intimal thickening. CONCLUSIONS:
      Alloimmune injury induces the expression of PDGF ligands, especially of PDGF-AA,
      in the graft vasculature and sufficient immunosuppression with CsA suppresses the
      expression of PDGF and inhibits the development of CAV. PDGF may have a
      substantial role in the regulation of smooth muscle cell migration and
      proliferation in an autocrine or paracrine manner during the development of CAV.

PMID- 9286956
TI  - Additional hypotensive effect of endothelin-1 receptor antagonism in hypertensive
      dogs under angiotensin-converting enzyme inhibition.
AB  - BACKGROUND: Endothelin-1 (ET-1) may play a role in hypertension. ET-1 receptor
      antagonism by bosentan lowers blood pressure in hypertension. We evaluated
      whether the effect of bosentan is still observed under ACE inhibitors (ACEI).
      METHODS AND RESULTS: Thirty anesthetized and 18 conscious hypertensive dogs were
      studied randomly. Anesthetized dogs were divided into 4 groups: group 1 received
      cumulative doses of bosentan (bolus+30-minute infusion: 0.1 mg/kg+/-0.23 mg/kg
      per hour to 3 mg/kg+/-7 mg/kg per hour); group 2, the same dose-responses after 1
      mg/kg enalaprilat; group 3, the vehicle after enalaprilat; and group 4, the dose
      responses to bosentan followed by enalaprilat. The conscious dogs were divided
      into 3 groups: group 5 received 2 cumulative doses of bosentan; group 6, the
      vehicle; and group 7, enalaprilat alone. In groups 1 and 2, bosentan produced
      dose-related decreases (P=.0001) in left ventricular systolic pressure and mean
      aortic pressure (AOP). In group 1, bosentan decreased mean AOP by 22%. In group
      2, enalaprilat decreased mean AOP by 25% (from 173+/-26 to 130+/-25 mm Hg;
      P<.005); an additional 18% decrease was obtained with bosentan, the mean AOP
      reaching 98+/-21 mm Hg (P<.01). In group 3, the effect of enalaprilat alone was a
      22% decrease in mean AOP (P<.005). The additive effect of the bosentan-ACEI
      association was also observed in group 4. In group 5, bosentan reduced mean AOP
      by 20% (P<.005), whereas mean AOP remained unchanged in group 6. The effect of
      ACEI alone (group 7) was similar to that of bosentan. CONCLUSIONS: Bosentan
      produces an additional hypotensive effect to that of ACEI, which opens new
      therapeutic perspectives.

PMID- 9286958
TI  - Regional alteration of the transient outward current in human left ventricular
      septum during compensated hypertrophy.
AB  - BACKGROUND: A large calcium-insensitive transient outward current (I(to)) has
      been recorded in atria, left ventricular (LV) free wall, and right ventricular
      septal subendocardium of the human heart. Recent studies suggested a major
      contribution of this current to the electrical heterogeneity of the heart.
      However, no data have been reported on the distribution of I(to) density within
      the LV septal wall from compensated human LV hypertrophy. METHODS AND RESULTS:
      Microelectrode and patch-clamp techniques were used to record action potentials
      and I(to) in myocytes isolated from superficial (<3 mm deep) and deep (3 to 6 mm
      deep) layers of LV septum from patients with aortic stenosis and compensated LV
      hypertrophy. Subendocardial specimens were also obtained from undiseased donor
      hearts. In none of the superficial subendocardial cells from diseased hearts was
      a macroscopic I(to) recorded (n=42), whereas in cells from the same location from
      donor hearts, a typical I(to) was clearly present, with a peak density of 5.88+/
      0.78 pA/pF at +60 mV (n=4). However, in deep layers from patients with
      compensated LV hypertrophy, macroscopic I(to) was present, with a peak density of
      10.50+/-2.58 pA/pF at +60 mV (n=4). The absence of I(to) in superficial septal
      cells from hypertrophied hearts was not due to a divalent cation-related shift of
      the current kinetics. Instead, extracellular Ca2+ removal induced an I(to)-like
      current, possibly carried by K+ ions, with a peak density of 30.7+/-2.6 pA/pF at
      +60 mV (n=29). However, its magnitude, kinetics, and pharmacological
      characteristics did not allow identification of this current as the usual I(to).
      CONCLUSIONS: Both topography and pathology can be major modulating factors of the
      regional distribution of I(to) density in human LV septum. Therefore, they may
      play a prominent role in determining electrical gradients within this region from
      which the early depolarization vectors start and the left-to-right activation
      sequence of the interventricular septum proceeds.

PMID- 9286957
TI  - Role of intracellular Ca2+ in activation of protein kinase C during ischemic
      preconditioning.
AB  - BACKGROUND: Activation of protein kinase C plays an important role in ischemic
      preconditioning. Given that protein kinase C is activated by an increase in the
      intracellular Ca2+ concentration ([Ca2+]i) and that myocardial ischemia and
      reperfusion increase [Ca2+]i, the effect of transient exposures to Ca2+ on
      infarct size and the effect of administration of EGTA during ischemic and alpha1
      adrenoceptor-mediated preconditioning on the limitation of infarct size were
      investigated in the canine heart. METHODS AND RESULTS: In open-chest dogs, 5
      minutes after the completion of either three 5-minute infusions of CaCl2 or four
      5-minute infusions of the alpha1-adrenoceptor agonist methoxamine into the
      coronary artery, the coronary arteries were occluded for 90 minutes; this
      occlusion was followed by a 6-hour reperfusion in both the Ca2+ preconditioning
      and methoxamine groups. Infarct sizes in the Ca2+ preconditioning (15.8+/-2.3%)
      and methoxamine (10.1+/-2.2%) groups were significantly (P<.01) smaller than in
      the control group (42.5+/-2.9%), and administration of either an inhibitor of
      protein kinase C (GF109203X) or an inhibitor of ecto-5'-nucleotidase (alpha,beta
      methyleneadenosine 5'-diphosphate) reduced the infarct size-limiting effect of
      Ca2+ preconditioning. Administration of EGTA during ischemic or alpha1
      adrenoceptor-mediated preconditioning inhibited both the infarct size-limiting
      effect and the activation of protein kinase C and ecto-5'-nucleotidase induced by
      these procedures. CONCLUSIONS: [Ca2+]i during ischemic and alpha1-adrenoceptor
      mediated preconditioning plays an important role in the infarct size-limiting
      effect of these procedures by activating protein kinase C and ecto-5'
      nucleotidase in the canine heart.

PMID- 9286959
TI  - Withdrawal of acetylcholine elicits Ca2+-induced delayed afterdepolarizations in
      cat atrial myocytes.
AB  - BACKGROUND: Recent experiments in atrial myocytes indicate that withdrawal of
      cholinergic agonist can directly increase Ca2+ influx via L-type Ca2+ current and
      stimulate Ca2+ uptake into the sarcoplasmic reticulum (SR), thereby increasing
      intracellular Ca2+. Overload of cellular Ca2+ within the SR can initiate various
      types of atrial dysrhythmias. The present study was designed to determine whether
      withdrawal of acetylcholine (ACh) can elicit Ca2+-induced delayed
      afterdepolarizations (DADs) in atrial myocytes. METHODS AND RESULTS: A nystatin
      perforated-patch whole-cell method and fluorescence microscopy (indo 1) were used
      to measure electrical activities and intracellular free Ca2+ ([Ca2+]i),
      respectively. Withdrawal of ACh (1 micromol/L) increased action potential
      duration, shifted plateau voltage toward positive, and generated DADs that
      initiated spontaneous action potentials. Voltage-clamp analysis revealed that
      withdrawal of ACh elicited a rebound stimulation of L-type Ca2+ current (I(Ca,L))
      (+45%) and Na/Ca exchange current (I(NaCa)) (+16%) and the appearance of
      transient inward current (I(ti)) and spontaneous [Ca2+]i transients. Each of
      these changes induced by withdrawal of ACh was abolished by Rp-cAMPs (50 to 100
      micromol/L) or H-89 (2 micromol/L), inhibitors of cAMP-dependent protein kinase
      A. Ryanodine (1 micromol/L) abolished I(NaCa) and the appearance of I(ti) without
      decreasing the rebound stimulation of I(Ca,L) elicited by withdrawal of ACh.
      CONCLUSIONS: Withdrawal of ACh can elicit cAMP-mediated stimulation of Ca2+
      influx via I(Ca,L) and uptake of SR Ca2+. As a result, cellular Ca2+ overload
      causes enhanced SR Ca2+ release and the initiation of DADs. These mechanisms may
      generate triggered and/or spontaneous atrial depolarizations elicited by
      withdrawal of vagal nerve activity.

PMID- 9286960
TI  - Dietary L-arginine reduces the progression of atherosclerosis in cholesterol-fed
      rabbits: comparison with lovastatin.
AB  - BACKGROUND: We investigated whether L-arginine induces regression of preexisting
      atheromatous lesions and reversal of endothelial dysfunction in
      hypercholesterolemic rabbits, whether similar effects can be obtained by
      cholesterol-lowering therapy with lovastatin, and which mechanism leads to these
      effects. METHODS AND RESULTS: Rabbits were fed 1% cholesterol for 4 weeks and
      0.5% cholesterol for an additional 12 weeks. Two groups of cholesterol-fed
      rabbits were treated with L-arginine (2.0% in drinking water) or lovastatin (10
      mg/d) during weeks 5 through 16. Systemic nitric oxide (NO) formation was
      assessed as the urinary excretion rates of nitrate and cGMP in weekly intervals.
      Cholesterol feeding progressively reduced urinary nitrate excretion to
      approximately 40% of baseline (P<.05) and increased plasma concentrations of
      asymmetrical dimethylarginine (ADMA), an endogenous NO synthesis inhibitor.
      Dietary L-arginine reversed the reduction in plasma L-arginine/ADMA ratio and
      partly restored urinary excretion of nitrate and cGMP (each P<.05 vs cholesterol)
      but did not change plasma cholesterol levels. L-Arginine completely blocked the
      progression of carotid intimal plaques, reduced aortic intimal thickening, and
      preserved endothelium-dependent vasodilator function. Lovastatin treatment
      reduced plasma cholesterol by 32% but did not improve urinary nitrate or cGMP
      excretion or endothelium-dependent vasodilation. Lovastatin had a weaker
      inhibitory effect on carotid plaque formation and aortic intimal thickening than
      L-arginine. L-Arginine inhibited but lovastatin potentiated superoxide radical
      generation in the atherosclerotic vascular wall. CONCLUSIONS: Dietary L-arginine
      improves NO-dependent vasodilator function in cholesterol-fed rabbits and
      completely blocks the progression of plaques via restoration of NO synthase
      substrate availability and reduction of vascular oxidative stress. Lovastatin
      treatment has a weaker inhibitory effect on the progression of atherosclerosis
      and no effect on vascular NO elaboration, which may be due to its stimulatory
      effect on vascular superoxide radical generation.

PMID- 9286961
TI  - Rat arterial wall retains myointimal hyperplastic potential long after arterial
      injury.
AB  - BACKGROUND: Many novel molecular and pharmacological modalities have been
      proposed for the treatment of accelerated vascular diseases. Yet the fundamental
      question remains of whether the vessel wall can be treated once only or whether
      single-dose therapy simply delays the inevitable processes that lead to intimal
      hyperplasia. Since platelet adhesion and aggregation are critical events in
      vascular healing, we sought to determine whether the injured blood vessel would
      retain its myointimal potential after reversal of even prolonged periods of
      thrombocytopenia. METHODS AND RESULTS: A novel nonimmune method sustained
      thrombocytopenia and suppressed postinjury neointimal hyperplasia by 88%.
      Infusion of fresh platelets, even 14 days after initial denuding injury, restored
      the full neointimal hyperplastic potential. Platelet depletion presumably removed
      factors chemotactic for vascular smooth muscle cells but had no effect on the
      overexpression of the platelet-derived growth factor receptor-beta (PDGFR-beta)
      subunit after vascular injury. In native vessels, 26.5+/-2.5% of medial smooth
      muscle cells expressed PDGFR-beta. In all animals, medial PDGFR-beta expression
      doubled 2 weeks after endothelial denudation and was evident in up to 74.5+/-2.5%
      of the cells forming the neointima. CONCLUSIONS: Thus, though the hyperplastic
      potential of the injured blood vessel can be delayed with removal of growth
      stimuli, it is not lost forever, and if the media is not made quiescent,
      neointimal hyperplasia is simply delayed rather than prevented. These results may
      have a profound effect on our understanding and treatment of accelerated
      proliferative vascular diseases.

PMID- 9286962
TI  - Inhibition of von Willebrand factor binding to platelet GP Ib by a fractionated
      aurintricarboxylic acid prevents restenosis after vascular injury in hamster
      carotid artery.
AB  - BACKGROUND: Aurintricarboxylic acid (ATA) prevents von Willebrand factor binding
      to platelet glycoprotein (GP) Ib, with higher-molecular-weight ATA more effective
      than the lower-molecular-weight compound. We investigated the effects of high
      molecular-weight ATA (Mr=7500), obtained by fractionating commercial ATA, in the
      injured hamster carotid artery. METHODS AND RESULTS: Platelet aggregation was
      induced in vitro with ADP (2.5 micromol/L) or botrocetin (5 microg/mL) in hamster
      platelet-rich plasma. IC50 values were 348.6+/-22.4 and 8.2+/-3.2 microg/mL,
      respectively. The endothelium of hamster carotid artery was denuded with a
      modified catheter. Continuous administration of high-molecular-weight ATA (10,
      30, and 100 microg x kg(-1) x h(-1)) with an infusion pump produced
      antithrombotic effects in a dose-dependent manner, as evaluated by prolongation
      of time to occlusion. Neointima formation was observed 2 weeks after
      catheterization, and proliferating smooth muscle cells (SMCs) were identified by
      the thymidine analogue 5-bromo-2-deoxyuridine (BrdU). Continuous treatment with
      the compound (100 microg x kg(-1) x h(-1)) with a 2ML1 Alzet infusion pump
      resulted in a reduction of neointimal area by 38.0+/-8.8% and decreased the BrdU
      index on days 1 and 7 significantly. DNA synthesis in DDT1MF2 hamster SMCs was
      also decreased by the compound in a dose-dependent manner. In histological
      observation, the process of endothelial healing was improved by this treatment
      with the compound. CONCLUSIONS: Inhibition of platelet adhesion by von Willebrand
      factor binding to platelet GP Ib by high-molecular-weight ATA results in the
      prevention of thrombus formation and the suppression of neointima lesion. In
      addition, high-molecular-weight ATA has an inhibitory effect on SMC
      proliferation. This inhibition of both platelet adhesion and SMC proliferation
      markedly reduced vascular stenosis.

PMID- 9286964
TI  - Failure to maintain a low ADP concentration impairs diastolic function in
      hypertrophied rat hearts.
AB  - BACKGROUND: Mechanisms in addition to diastolic calcium overload may contribute
      to diastolic dysfunction in hypertrophied hearts. In this study, we tested the
      hypothesis that failure to maintain a low ADP concentration in hypertrophied
      hearts contributes to diastolic dysfunction by inhibiting the rate of cross
      bridge cycling. METHODS AND RESULTS: By perfusing isolated rat hearts with
      pyruvate and 2-deoxyglucose (2DG), we were able to perturb [ADP] with minimal
      changes in [ATP] and [inorganic phosphate] or the contribution of glycolytic ATP
      to ATP synthesis. The effects of 2DG were compared in aortic-banded (LVH, n=5)
      and sham-operated (control, n=5) rat hearts. 31P NMR spectroscopy was used to
      measure the concentrations of phosphorus-containing compounds. We found a
      threefold increase of left ventricular end-diastolic pressure (LVEDP) in LVH
      during 2DG perfusion, and this increase was concomitant with a threefold increase
      in intracellular free [ADP]. The [ADP] in the control hearts was maintained <40
      micromol/L, and no change in LVEDP was observed. A linear relationship between
      increases in [ADP] and LVEDP was found (r2=.66, P=.001). Furthermore, the
      capacity of the creatine kinase reaction, a major mechanism for maintaining a low
      [ADP], was decreased in LVH (P=.0001). CONCLUSIONS: Increased [ADP] contributes
      to diastolic dysfunction in LVH, possibly due to slowed cross-bridge cycling.
      Decreased capacity of the creatine kinase reaction to rephosphorylate ADP is a
      likely contributing mechanism to the failure to maintain a low [ADP] in LVH.

PMID- 9286965
TI  - Basal release of nitric oxide augments the Frank-Starling response in the
      isolated heart.
AB  - BACKGROUND: The Frank-Starling response contributes to the regulation of cardiac
      output. The major underlying subcellular mechanism is a length-dependent change
      in myofilament responsiveness to Ca2+. Recent studies indicate that nitric oxide
      decreases myofilament responsiveness to Ca2+ and modulates myocardial relaxation
      and left ventricular (LV) diastolic function. We therefore investigated the
      interaction between nitric oxide and the Frank-Starling response. METHODS AND
      RESULTS: Isolated ejecting guinea pig hearts (constant afterload and heart rate)
      were studied before and after interventions. Elevation of filling pressure from
      10 to 20 cm H2O increased cardiac output, LV end-diastolic pressure (LVEDP), and
      peak LV pressure (LVPmax). In the presence of N(G)-monomethyl-L-arginine (L-NMMA,
      10 micromol/L; n=10) or free hemoglobin (1 micromol/L; n=8), preload-induced
      increases in cardiac output were significantly attenuated but baseline cardiac
      output was unaffected. The effects of L-NMMA were inhibited in the presence of
      excess L-arginine (100 micromol/L; n=6). These changes were not attributable to
      alterations in coronary flow. Prostaglandin F2alpha (0.01 micromol/L; n=6), which
      reduced coronary flow, failed to alter the cardiac output response to preload
      elevation. The exogenous nitric oxide donor sodium nitroprusside (1 micromol/L;
      n=6) reduced cardiac output at the lowest preload but not at higher preloads.
      LVEDP was elevated after L-NMMA and hemoglobin but reduced after sodium
      nitroprusside. CONCLUSIONS: Basal intracardiac production of nitric oxide
      significantly augments preload-induced rises in cardiac output in the isolated
      ejecting guinea pig heart. The mechanism appears to be unrelated to changes in
      coronary flow and may involve direct effects of nitric oxide on myocardial
      diastolic and/or systolic function.

PMID- 9286966
TI  - Regression of left ventricular hypertrophy with captopril restores normal
      ventricular action potential duration, dispersion of refractoriness, and
      vulnerability to inducible ventricular fibrillation.
AB  - BACKGROUND: Left ventricular hypertrophy (LVH) is associated with multiple
      cellular electrophysiological abnormalities, susceptibility to ventricular
      arrhythmias, and an increased risk of sudden death. Several pharmacological
      therapies have been shown to produce regression of hypertrophy, but the value of
      regression is unclear. The present study examines whether pharmacological
      regression of LVH has effects on the susceptibility to ventricular arrhythmia or
      the cellular electrophysiological abnormalities of LVH. METHODS AND RESULTS:
      Rabbits underwent unilateral renal artery banding and contralateral nephrectomy
      to induce LVH or were placed in the control group. Both groups were studied 3
      months later by in vivo and in vitro electrophysiological techniques. Banded
      rabbits had increased mean arterial pressure, increased left ventricular weight
      and wall thickness, increased dispersion of refractoriness, and lower ventricular
      fibrillation thresholds than control rabbits. Action potential duration and cell
      capacitance were also greater in the banded group. Additional rabbits were
      treated beginning 3 months after banding with either captopril (5 mg x kg(-1) x
      d(-1)) or vehicle added to their diet for an additional 3 months. These rabbits
      and age-matched controls were then studied by in vivo and in vitro
      electrophysiological techniques. In banded rabbits that received vehicle and were
      studied 6 months after banding, increased dispersion of refractoriness, a lower
      ventricular fibrillation threshold, and action potential prolongation persisted
      and were unchanged from animals studied 3 months after banding. Captopril,
      started 3 months after banding, caused regression of hypertrophy and
      normalization of the in vivo and in vitro electrophysiological abnormalities.
      Addition of captopril to the tissue bath during in vitro electrophysiological
      study showed no effect on cells from control or banded rabbits. CONCLUSIONS:
      Pharmacological regression of LVH with captopril normalizes the in vivo and in
      vitro electrophysiological abnormalities of ventricular hypertrophy and reduces
      the vulnerability to ventricular fibrillation in a renovascular model of LVH.

PMID- 9286963
TI  - Is calcium a mediator of infarct size reduction with preconditioning in canine
      myocardium?
AB  - BACKGROUND: The cellular mechanisms by which brief episodes of ischemia protect
      or "precondition" the heart and limit infarct size caused by a later period of
      sustained coronary artery occlusion remain unresolved. We propose that calcium
      may be an important mediator in eliciting this cardioprotection. METHODS AND
      RESULTS: To test this hypothesis, anesthetized dogs received a 15-minute
      intracoronary infusion of 20 mmol/L CaCl2 or saline before undergoing 1 hour of
      coronary occlusion and 4 hours of reperfusion (protocol 1). Collateral blood flow
      during occlusion was measured with radiolabeled microspheres, area at risk of
      infarction (AR) was delineated by injection of blue dye, and area of necrosis
      (AN) was determined by tetrazolium staining. AN/AR was reduced from 20+/-5% in
      the saline-treated controls to 9+/-3% in CaCl2-treated dogs (P<.05). Additional
      animals underwent 10 minutes of preconditioning ischemia or a comparable waiting
      period before the 1-hour test occlusion (protocol 2). Administration of 5-(N,N
      dimethyl)-amiloride (an inhibitor of calcium influx via Na+-H+ and Na+-Ca2+
      exchange) before the preconditioning stimulus attenuated the protective effect of
      ischemic preconditioning: AN/AR was 12+/-1%, larger than the value of 4+/-1%
      observed in preconditioned dogs that received saline (P<.05) and comparable to
      the values of 12+/-3% and 14+/-3% seen in saline- and dimethylamiloride-treated
      controls. CONCLUSIONS: Brief intracoronary infusion of CaCl2 mimicked, whereas
      treatment with dimethylamiloride blocked, infarct size reduction with
      preconditioning, thereby implicating calcium as a mediator of preconditioning in
      this canine model.

PMID- 9286968
TI  - Safety of transvenous atrial defibrillation: studies in the canine sterile
      pericarditis model.
AB  - BACKGROUND: It is recognized that a ventricular vulnerability period exists
      during which atrial shock delivery may induce a ventricular tachyarrhythmia. This
      study was designed to define the zone in which the ventricles are vulnerable to
      induction of ventricular tachyarrhythmia during delivery of atrial shocks in the
      sterile pericarditis canine model of atrial fibrillation. METHODS AND RESULTS:
      Two days after creation of sterile pericarditis, 24 dogs underwent either a four
      part or five-part ventricular vulnerability protocol during which atrial shocks
      were delivered between transvenous catheters, one in the distal coronary sinus
      and one in the right atrial appendage. The protocol included part 1, shocks
      during induced atrial fibrillation; parts 2 through 4, shocks delivered
      synchronously with the last ventricular beat of one of the following three
      ventricular pacing protocols: constant ventricular rates (S1S1), short-long-short
      cycles (S1S2S3-V), and ventricular premature beats (S1); and part 5, shocks
      delivered synchronously with the last R wave resulting from an atrially paced
      short-long-short cycle (S1S2S3-A). Ventricular tachyarrhythmia was induced 122
      times: 2 of 665 shocks in two dogs in part 1, 29 of 786 shocks in nine dogs in
      part 2, 67 of 734 shocks in 15 dogs in part 3, 24 of 919 shocks in five dogs in
      part 4, and none in part 5. All ventricular proarrhythmia resulted from shocks
      delivered during the T wave of a preceding ventricular beat. No episodes of
      ventricular tachyarrhythmia were induced by atrial shocks synchronized to R waves
      with the previous RR at intervals above the QT+60 ms interval (absolute interval
      >320 ms), with one exception, at the QT+100 ms interval (absolute interval 360
      ms). CONCLUSIONS: With transvenous electrode catheters used to deliver atrial
      shocks, life-threatening ventricular rhythms were induced but were limited to a
      specific zone defined by the QT interval.

PMID- 9286967
TI  - Heterogeneous sympathetic innervation in German shepherd dogs with inherited
      ventricular arrhythmia and sudden cardiac death.
AB  - BACKGROUND: Recently, a colony of German shepherd dogs with inherited spontaneous
      cardiac arrhythmias and associated sudden death has been developed and
      characterized. Due to the median age of onset of the arrhythmia (4.5 months), the
      tendency for the arrhythmia to occur during REM sleep or after exercise, and the
      absence of structural heart disease, we hypothesized a developmental abnormality
      of the sympathetic innervation to the heart. METHODS AND RESULTS: We studied 11
      dogs from this colony, ranging in age from 6 months to 6 years, and four 7-month
      old German shepherd dogs unrelated to the colony as controls. We imaged the
      distribution of functional myocardial sympathetic innervation and perfusion with
      [123I]metaiodobenzylguanidine (MIBG) and 201Tl, respectively. Sympathetic nerve
      distribution was evaluated morphologically by immunocytochemical localization of
      tyrosine hydroxylase. All of the hearts showed evidence of a regional decrease in
      MIBG uptake, ranging from 5.3% to 53.4% of the myocardium, whereas control dogs
      showed homogeneous MIBG uptake. Immunocytochemical studies on sections from
      regions with decreased MIBG uptake showed a striking paucity of nerves compared
      with regions with normal MIBG uptake, confirming denervation. When the dogs were
      grouped into those with (n=6) and without (n=5) evidence of ventricular
      tachycardia on ambulatory ECG, the group with ventricular tachycardia showed 35+/
      16.5% denervation, whereas the group without ventricular tachycardia showed 12+/
      5.6% denervation (P<.02). CONCLUSIONS: Abnormal heterogeneous sympathetic
      innervation exists in these dogs with inherited ventricular arrhythmia and sudden
      cardiac death. Mechanisms relating the presence and extent of regional
      denervation to the incidence of ventricular arrhythmia remain to be defined.

PMID- 9286969
TI  - Effects of transvenous electrode polarity and waveform duration on the
      relationship between defibrillation threshold and upper limit of vulnerability.
AB  - BACKGROUND: The upper limit of vulnerability (ULV) hypothesis for defibrillation
      predicts that maneuvers that alter the ULV will cause a similar alteration in the
      defibrillation threshold (DFT). The purpose of this study was to test this
      prediction by evaluating the effects of electrode polarity and waveform duration
      on the relationship between the DFT and the ULV. METHODS AND RESULTS: Platinum
      spring electrodes were placed in the right ventricular (RV) apex and the superior
      vena cava in 12 pigs. Strength-duration curves were constructed for the DFT and
      ULV for each electrode polarity with monophasic waveforms (6 pigs) of different
      durations (2 to 14 ms) and biphasic truncated exponential waveforms (6 pigs)
      having phase 1 equal to 4 ms and phase 2 of different durations (0 to 10 ms). ULV
      data were gathered by scanning of the T wave. The ventricular pacing threshold
      (VPT) and ventricular fibrillation threshold (VFT) were also determined with
      these same waveforms. For the RV electrode as a cathode for monophasic and the
      first phase of biphasic stimuli, VPTs for the same waveform duration were
      significantly lower than for the configuration with the RV electrode as an anode.
      VFTs were not significantly different for the two electrode polarities with
      either monophasic or biphasic waveforms. The DFT changed in a fashion similar to
      the ULV with changes in electrode polarity and phase duration for both monophasic
      and biphasic waveforms. The ULV and DFT for each waveform duration for each
      polarity were strongly correlated (r=.83 to .99). CONCLUSIONS: The almost
      identical changes in ULV and DFT with changes in electrode polarity and waveform
      duration provide new evidence to support the ULV hypothesis of defibrillation.

PMID- 9286970
TI  - Lipid lowering versus revascularization: an idea whose time (for testing) has
      come.
AB  - There is strong evidence that revascularization does not prevent myocardial
      infarction in patients with stable coronary artery disease (CAD). The anatomic
      basis for this counterintuitive conclusion seems to be that most myocardial
      infarctions occur at sites that did not previously exhibit an angiographically
      significant stenosis. These angiographic observations are further supported by
      thallium studies in stable CAD that demonstrate that the site of stress-induced
      ischemia is frequently not the site of subsequent myocardial infarction. Since
      both coronary artery bypass graft surgery and percutaneous transluminal coronary
      angioplasty are directed at more severe coronary stenoses, we are led to the
      remarkable conclusion that angiography does not identify, and consequently
      revascularization therapies do not treat, the lesions that lead to myocardial
      infarction. The pathology of coronary atherosclerosis provides the basis for
      understanding why revascularization does not prevent infarction: unstable lesions
      that cause infarction are not necessarily severely stenotic, and stenotic lesions
      are not necessarily unstable. In contrast to revascularization, lipid lowering
      reduces the rate of myocardial infarction by approximately 30% over a period of 5
      years. Thus, we might postulate that lipid lowering is the more effective therapy
      for both prevention of acute myocardial infarction and long-term survival. The
      health policy and economic implications of this viewpoint, should it emerge in
      the management of coronary heart disease, are clearly substantial. Consequently,
      the relative roles of lipid-lowering therapy and revascularization, both alone
      and together, must now be determined. It is an idea whose time--for testing--has
      come.

PMID- 9286971
TI  - Images in cardiovascular medicine: Chagas' disease and ventricular aneurysms.

PMID- 9286972
TI  - Images in cardiovascular medicine: complete heart block.

PMID- 9286974
TI  - Transcription of Staphylococcus aureus fibronectin binding protein genes is
      negatively regulated by agr and an agr-independent mechanism.
AB  - The production of cell surface proteins in Staphylococcus aureus is generally
      down-regulated in the postexponential growth phase by the global regulator agr.
      The effector of this regulation is the RNAIII molecule, which is encoded within
      the agr locus. RNAIII seems to regulate most target genes at the level of
      transcription, but it also has an effect on the translation of some genes. To
      study the role of agr on the expression of fibronectin binding proteins (FnBPs),
      we investigated the transcription and translation of fnb genes in agr mutant
      strain WA250 and its parent strain, 8325-4. The results show that fnb genes are
      negatively regulated by agr and also by an agr-independent mechanism that
      restricts fnb mRNA synthesis to the early exponential phase of growth.
      Transcription and Western blot analysis of cell-associated FnBPs demonstrated
      that synthesis of both FnBPA and FnBPB in the wild-type and agr mutant strains
      took place preferentially during the first hour of growth and rapidly decreased
      after the second hour. We also confirmed previous results showing that the agr
      mutant strain has an increased capacity to bind fibronectin compared to its
      parent agr+ strain. However, while the concentrations of fnb mRNAs and proteins
      differed by a factor of 16 between the strains, the difference in fibronectin
      binding was only twofold, indicating that the binding of fibronectin to the
      bacteria is not proportional to the amount of FnBPs on their surface.

PMID- 9286973
TI  - Structure of the puf operon of the obligately aerobic, bacteriochlorophyll alpha
      containing bacterium Roseobacter denitrificans OCh114 and its expression in a
      Rhodobacter capsulatus puf puc deletion mutant.
AB  - Roseobacter denitrificans (Erythrobacter species strain OCh114) synthesizes
      bacteriochlorophyll a (BChl) and the photosynthetic apparatus only in the
      presence of oxygen and is unable to carry out primary photosynthetic reactions
      and to grow photosynthetically under anoxic conditions. The puf operon of R.
      denitrificans has the same five genes in the same order as in many photosynthetic
      bacteria, i.e., pufBALMC. PufC, the tetraheme subunit of the reaction center
      (RC), consists of 352 amino acids (Mr, 39,043); 20 and 34% of the total amino
      acids are identical to those of PufC of Chloroflexus aurantiacus and Rubrivivax
      gelatinosus, respectively. The N-terminal hydrophobic domain is probably
      responsible for anchoring the subunit in the membrane. Four heme-binding domains
      are homologous to those of PufC in several purple bacteria. Sequences similar to
      pufQ and pufX of Rhodobacter capsulatus were not detected on the chromosome of R.
      denitrificans. The puf operon of R. denitrificans was expressed in trans in
      Escherichia coli, and all gene products were synthesized. The Roseobacter puf
      operon was also expressed in R. capsulatus CK11, a puf puc double-deletion
      mutant. For the first time, an RC/light-harvesting complex I core complex was
      heterologously synthesized. The strongest expression of the R. denitrificans puf
      operon was observed under the control of the R. capsulatus puf promoter, in the
      presence of pufQ and pufX and in the absence of pufC. Charge recombination
      between the primary donor P+ and the primary ubiquinone Q(A)- was observed in the
      transconjugant, showing that the M and L subunits of the RC were correctly
      assembled. The transconjugants did not grow photosynthetically under anoxic
      conditions.

PMID- 9286975
TI  - FnrN controls symbiotic nitrogen fixation and hydrogenase activities in Rhizobium
      leguminosarum biovar viciae UPM791.
AB  - Rhizobium leguminosarum bv. viciae UPM791 contains a second copy of the fnrN
      gene, which encodes a redox-sensitive transcriptional activator functionally
      homologous to Escherichia coli Fnr. This second copy (fnrN2) is located in the
      symbiotic plasmid, while fnrN1 is in the chromosome. Isolation and sequencing of
      the fnrN2 gene revealed that the deduced amino acid sequence of FnrN2 is 87.5%
      identical to the sequence of FnrN1, including a conserved cysteine-rich motif
      characteristic of Fnr-like proteins. Individual R. leguminosarum fnrN1 and fnrN2
      mutants exhibited a Fix+ phenotype and near wild-type levels of nitrogenase and
      hydrogenase activities in pea (Pisum sativum L.) nodules. In contrast, an fnrN1
      fnrN2 double mutant formed ineffective nodules lacking both nitrogenase and
      hydrogenase activities. Unlike the wild-type strain and single fnrN1 or fnrN2
      mutants, the fnrN1 fnrN2 double mutant was unable to induce micro-oxic or
      bacteroid activation of the hypBFCDEX operon, which encodes proteins essential
      for hydrogenase synthesis. In the search for symbiotic genes that could be
      controlled by FnrN, a fixNOQP operon, putatively encoding a micro-oxically
      induced, bacteroid-specific cbb3-type terminal cytochrome oxidase, was isolated
      from strain UPM791 and partially sequenced. The fixNOQP operon was present in a
      single copy located in the symbiotic plasmid, and an anaerobox was identified in
      the fixN promoter region. Consistent with this, a fixNOQP'-lacZ fusion was shown
      to be highly induced in micro-oxic cells of the wild-type strain. A high level of
      micro-oxic induction was also observed in single fnrN1 and fnrN2 mutants, but no
      detectable induction was observed in the fnrN1 fnrN2 double mutant. The lack of
      expression of fixNOQP in the fnrN1 fnrN2 double mutant is likely to cause the
      observed Fix- phenotype. These data demonstrate that, contrary to the situation
      in other rhizobia, FnrN controls both hydrogenase and nitrogenase activities of
      R. leguminosarum bv. viciae UPM791 in the nodule and suggest that this strain
      lacks a functional fixK gene.

PMID- 9286977
TI  - Control of the shift from homolactic acid to mixed-acid fermentation in
      Lactococcus lactis: predominant role of the NADH/NAD+ ratio.
AB  - During batch growth of Lactococcus lactis subsp. lactis NCDO 2118 on various
      sugars, the shift from homolactic to mixed-acid metabolism was directly dependent
      on the sugar consumption rate. This orientation of pyruvate metabolism was
      related to the flux-controlling activity of glyceraldehyde-3-phosphate
      dehydrogenase under conditions of high glycolytic flux on glucose due to the
      NADH/NAD+ ratio. The flux limitation at the level of glyceraldehyde-3-phosphate
      dehydrogenase led to an increase in the pool concentrations of both
      glyceraldehyde-3-phosphate and dihydroxyacetone-phosphate and inhibition of
      pyruvate formate lyase activity. Under such conditions, metabolism was
      homolactic. Lactose and to a lesser extent galactose supported less rapid growth,
      with a diminished flux through glycolysis, and a lower NADH/NAD+ ratio. Under
      such conditions, the major pathway bottleneck was most probably at the level of
      sugar transport rather than glyceraldehyde-3-phosphate dehydrogenase.
      Consequently, the pool concentrations of phosphorylated glycolytic intermediates
      upstream of glyceraldehyde-3-phosphate dehydrogenase decreased. However, the
      intracellular concentration of fructose-1,6-bisphosphate remained sufficiently
      high to ensure full activation of lactate dehydrogenase and had no in vivo role
      in controlling pyruvate metabolism, contrary to the generally accepted opinion.
      Regulation of pyruvate formate lyase activity by triose phosphates was relaxed,
      and mixed-acid fermentation occurred (no significant production of lactate on
      lactose) due mostly to the strong inhibition of lactate dehydrogenase by the in
      vivo NADH/NAD+ ratio.

PMID- 9286976
TI  - Quorum sensing in Aeromonas hydrophila and Aeromonas salmonicida: identification
      of the LuxRI homologs AhyRI and AsaRI and their cognate N-acylhomoserine lactone
      signal molecules.
AB  - Spent culture supernatants from both Aeromonas hydrophila and Aeromonas
      salmonicida activate a range of biosensors responsive to N-acylhomoserine
      lactones (AHLs). The genes for a quorum sensing signal generator and a response
      regulator were cloned from each Aeromonas species and termed ahyRI and asaRI,
      respectively. Protein sequence homology analysis places the gene products within
      the growing family of LuxRI homologs. ahyR and asaR are transcribed divergently
      from ahyI and asaI, respectively, and in both Aeromonas species, the genes
      downstream have been identified by DNA sequence and PCR analysis. Downstream of
      both ahyI and asaI is a gene with close homology to iciA, an inhibitor of
      chromosome replication in Escherichia coli, a finding which implies that in
      Aeromonas, cell division may be linked to quorum sensing. The major signal
      molecule synthesized via both AhyI and AsaI was purified from spent culture
      supernatants and identified as N-(butanoyl)-L-homoserine lactone (BHL) by thin
      layer chromatography, high-pressure liquid chromatography analysis, and mass
      spectrometry. In addition, a second, minor AHL, N-hexanoyl-L-homoserine lactone,
      was identified. Transcriptional reporter studies with ahyI::luxCDABE fusions
      indicate that AhyR and BHL are both required for ahyI transcription. For A.
      salmonicida, although the addition of exogenous BHL gives only a small
      stimulation of the production of serine protease with comparison to the control
      culture, the incorporation of a longer-chain AHL, N-(3-oxodecanoyl)-L-homoserine
      lactone, reduced the final level (by approximately 50%) and delayed the
      appearance (from an A650 of 0.9 in the control to an A650 of 1.2 in the test) of
      protease in the culture supernatant. These data add A. hydrophila and A.
      salmonicida to the growing family of gram-negative bacteria now known to control
      gene expression through quorum sensing.

PMID- 9286978
TI  - A homoserine lactone autoinducer regulates virulence of an insect-pathogenic
      bacterium, Xenorhabdus nematophilus (Enterobacteriaceae).
AB  - N-beta-Hydroxybutanoyl homoserine lactone (HBHL), the autoinducer of the
      luminescent system of Vibrio harveyi, has been identified as the first small
      compound to restore virulence to avirulent mutants of Xenorhabdus nematophilus.
      HBHL stimulated the level of lipase activity excreted by avirulent X.
      nematophilus and lowered the phenoloxidase activity in the hemolymph of insects
      infected with X. nematophilus, parameters that are both associated with insect
      pathogenesis. Moreover, mortality of the insects infected with avirulent X.
      nematophilus was restored upon injection with HBHL. Chloroform extraction of
      medium conditioned with wild-type but not avirulent X. nematophilus led to the
      isolation of a compound with the same chromatographic mobility as HBHL as well as
      the ability to stimulate the luminescence of a dim autoinducer-dependent mutant
      of V. harveyi. Transfer of the V. harveyi lux operon into avirulent and wild-type
      X. nematophilus generated dim and bright luminescent strains, respectively, which
      responded to HBHL and an agonist and antagonist in a manner analogous to their
      effects on the luminescence of dim autoinducer-deficient and bright wild-type
      strains of V. harveyi, indicating that similar HBHL-dependent regulatory systems
      exist in these two bacterial species.

PMID- 9286979
TI  - Identification and molecular characterization of two tandemly located flagellin
      genes from Aeromonas salmonicida A449.
AB  - Two tandemly located flagellin genes, flaA and flaB, with 79% nucleotide sequence
      identity were identified in Aeromonas salmonicida A449. The fla genes are
      conserved in typical and atypical strains of A. salmonicida, and they display
      significant divergence at the nucleotide level from the fla genes of the motile
      species Aeromonas hydrophila and Aeromonas veronii biotype sobria. flaA and flaB
      encode unprocessed flagellins with predicted Mrs of 32,351 and 32,056,
      respectively. When cloned under the control of the Ptac promoter, flaB was highly
      expressed when induced in Escherichia coli DH5alpha, and the FlaB protein was
      detectable even in the uninduced state. In flaA clones containing intact upstream
      sequence, FlaA was barely detectable when uninduced and poorly expressed on
      induction. The A. salmonicida flagellins are antigenically cross-reactive with
      the A. hydrophila TF7 flagellin(s) and evolutionarily closely related to the
      flagellins of Pseudomonas aeruginosa and Vibrio anguillarum. Electron microscopy
      showed that A. salmonicida A449 expresses unsheathed polar flagella at an
      extremely low frequency under normal laboratory growth conditions, suggesting the
      presence of a full complement of genes whose products are required to make
      flagella; e.g., immediately downstream of flaA and flaB are open reading frames
      encoding FlaG and FlaH homologs.

PMID- 9286981
TI  - Purification and characterization of an arginine regulatory protein, ArgR, from
      Pseudomonas aeruginosa and its interactions with the control regions for the car,
      argF, and aru operons.
AB  - Pseudomonas aeruginosa ArgR, a regulatory protein that plays a major role in the
      control of certain biosynthetic and catabolic arginine genes, was purified to
      homogeneity. ArgR was shown to be a dimer of two equal subunits, each with a
      molecular mass of 37,000 Da. Determination of the amino-terminal amino acid
      sequence showed it to be identical to that predicted from the derived sequence
      for the argR gene. DNase I footprinting showed that ArgR protects a region of 45
      to 47 bp that overlaps the promoters for the biosynthetic car and argF operons,
      indicating that ArgR exerts its negative control on the expression of these
      operons by steric hindrance. Studies were also carried out with the aru operon,
      which encodes enzymes of the catabolic arginine succinyl-transferase pathway.
      Quantitative S1 nuclease experiments showed that expression of the first gene in
      this operon, aruC, is initiated from an arginine-inducible promoter. Studies with
      an aruC::lacZ fusion showed that this promoter is under the control of ArgR.
      DNase I experiments indicated that ArgR protects two 45-bp binding sites upstream
      of aruC; the 3' terminus for the downstream binding site overlaps the -35 region
      for the identified promoter. Gel retardation experiments yielded apparent
      dissociation constants of 2.5 x 10(-11), 4.2 x 10(-12), and 7.2 x 10(-11) M for
      carA, argF, and aruC operators, respectively. Premethylation interference and
      depurination experiments with the car and argF operators identified a common
      sequence, 5'-TGTCGC-3', which may be important for ArgR binding. Alignment of
      ArgR binding sites reveals that the ArgR binding site consists of two half-sites,
      in a direct repeat arrangement, with the consensus sequence TGTCGCN8AAN5.

PMID- 9286980
TI  - Cloning and characterization of argR, a gene that participates in regulation of
      arginine biosynthesis and catabolism in Pseudomonas aeruginosa PAO1.
AB  - Gel retardation experiments indicated the presence in Pseudomonas aeruginosa cell
      extracts of an arginine-inducible DNA-binding protein that interacts with the
      control regions for the car and argF operons, encoding carbamoylphosphate
      synthetase and anabolic ornithine carbamoyltransferase, respectively. Both
      enzymes are required for arginine biosynthesis. The use of a combination of
      transposon mutagenesis and arginine hydroxamate selection led to the isolation of
      a regulatory mutant that was impaired in the formation of the DNA-binding protein
      and in which the expression of an argF::lacZ fusion was not controlled by
      arginine. Experiments with various subclones led to the conclusion that the
      insertion affected the expression of an arginine regulatory gene, argR, that
      encodes a polypeptide with significant homology to the AraC/XylS family of
      regulatory proteins. Determination of the nucleotide sequence of the flanking
      regions showed that argR is the sixth and terminal gene of an operon for
      transport of arginine. The argR gene was inactivated by gene replacement, using a
      gentamicin cassette. Inactivation of argR abolished arginine control of the
      biosynthetic enzymes encoded by the car and argF operons. Furthermore, argR
      inactivation abolished the induction of several enzymes of the arginine
      succinyltransferase pathway, which is considered the major route for arginine
      catabolism under aerobic conditions. Consistent with this finding and unlike the
      parent strain, the argR::Gm derivative was unable to utilize arginine or
      ornithine as the sole carbon source. The combined data indicate a major role for
      ArgR in the control of arginine biosynthesis and aerobic catabolism.

PMID- 9286982
TI  - Role of four major cellulases in triggering of cellulase gene expression by
      cellulose in Trichoderma reesei.
AB  - The relative contributions of four major cellulases of Trichoderma reesei (1,4
      beta-D-glucan cellobiohydrolase I [CBH I], CBH II, endo-1,4-beta-D-glucanase I
      [EG I], and EG II) to the generation of the cellulase inducer from cellulose were
      studied with isogenic strains in which the corresponding genes (cbh1, cbh2, egl1,
      and egl2) had been deleted by insertion of the Aspergillus nidulans amdS marker
      gene. During growth on lactose (a soluble carbon source provoking cellulase gene
      expression), these strains showed no significant alterations in their ability to
      express the respective other cellulase genes, with the exception of the strain
      containing delta cbh1, which exhibited an increased steady-state level of cbh2
      mRNA. On crystalline cellulose as the only carbon source, however, significant
      differences were apparent: strains in which cbh2 and egl2, respectively, had been
      deleted showed no expression of the other cellulase genes, whereas strains
      carrying the cbh1 or egl1 deletion showed these transcripts. The delta cbh1
      containing strain also showed enhanced cbh2 mRNA levels under these conditions. A
      strain in which both cbh1 and cbh2 had been deleted, however, was unable to
      initiate growth on cellulose. Addition of 2 mM sophorose, a putative inducer of
      cellulase gene expression, to such cultures induced the transcription of egl1 and
      egl2 and restored the ability to grow on cellulose. We conclude that CBH II and
      EG II are of major importance for the efficient formation of the inducer from
      cellulose in T. reesei and that removal of both cellobiohydrolases renders T.
      reesei unable to attack crystalline cellulose.

PMID- 9286983
TI  - The femR315 gene from Staphylococcus aureus, the interruption of which results in
      reduced methicillin resistance, encodes a phosphoglucosamine mutase.
AB  - The femR315 gene was recently identified by Tn551 insertional mutagenesis as one
      of the new auxiliary genes, the alteration of which resulted in a drastically
      reduced methicillin resistance of the Staphylococcus aureus strain COL. femR315
      (also known as femD) theoretically encoded a protein of 451 amino acids showing
      significant amino acid sequence homology with phosphoglucomutases and similar
      enzymes catalyzing the isomerization of hexoses and hexosamine phosphates (S. Wu,
      H. de Lencastre, A. Sali, and A. Tomasz, Microb. Drug Resist. 2:277-286, 1996).
      We describe here the overproduction and purification of the FemR315 protein as
      well as its identification as the phosphoglucosamine mutase which catalyzes the
      formation of glucosamine-1-phosphate from glucosamine-6-phosphate, the first step
      in the reaction sequence leading to the essential peptidoglycan precursor UDP-N
      acetylglucosamine. On the basis of these findings, we propose to change the names
      femR315 and femD to the functionally more appropriate name glmM.

PMID- 9286984
TI  - Fatty acid biosynthesis in Pseudomonas aeruginosa: cloning and characterization
      of the fabAB operon encoding beta-hydroxyacyl-acyl carrier protein dehydratase
      (FabA) and beta-ketoacyl-acyl carrier protein synthase I (FabB).
AB  - The Pseudomonas aeruginosa fabA and fabB genes, encoding beta-hydroxyacyl-acyl
      carrier protein dehydratase and beta-ketoacyl-acyl carrier protein synthase I,
      respectively, were cloned, sequenced, and expressed in Escherichia coli. Northern
      analysis demonstrated that fabA and fabB are cotranscribed and most probably form
      a fabAB operon. The FabA and FabB proteins were similar in size and amino acid
      composition to their counterparts from Escherichia coli and to the putative
      homologs from Haemophilus influenzae. Chromosomal fabA and fabB mutants were
      isolated; the mutants were auxotrophic for unsaturated fatty acids. A temperature
      sensitive fabA mutant was obtained by site-directed mutagenesis of a single base
      that induced a G101D change; this mutant grew normally at 30 degrees C but not at
      42 degrees C, unless the growth medium was supplemented with oleate. By physical
      and genetic mapping, the fabAB genes were localized between 3.45 and 3.6 Mbp on
      the 5.9-Mbp chromosome, which corresponds to the 58- to 59.5-min region of the
      genetic map.

PMID- 9286986
TI  - Redox buffering by melanin and Fe(II) in Cryptococcus neoformans.
AB  - Melanin is a fungal extracellular redox buffer which, in principle, can
      neutralize antimicrobial oxidants generated by immunologic effector cells, but
      its source of reducing equivalents is not known. We wondered whether Fe(II)
      generated by the external ferric reductase of fungi might have the physiologic
      function of reducing fungal melanin and thereby promoting pathogenesis. We
      observed that exposure of a melanin film electrode to reductants decreased the
      open-circuit potential (OCP) and reduced the area of a cyclic voltammetric
      reduction wave whereas exposure to oxidants produced the opposite effects.
      Exposure to 10, 100, 1,000 or 10,000 microM Fe(II) decreased the OCP of melanin
      by 0.015, 0.038, 0.100, and 0.120 V, respectively, relative to a silver-silver
      chloride standard, and decreased the area of the cyclic voltammetric reduction
      wave by 27, 35, 50, and 83%, respectively. Moreover, exposure to Fe(II) increased
      the buffering capacity by 44%, while exposure to millimolar dithionite did not
      increase the buffering capacity. The ratio of the amount of bound iron to the
      amount of the incremental increase in the following oxidation wave was
      approximately 1.0, suggesting that bound iron participates in buffering. Light
      absorption by melanin suspensions was decreased 14% by treatment with Fe(II),
      consistent with reduction of melanin. Light absorption by suspensions of
      melanized Cryptococcus neoformans was decreased 1.3% by treatment with Fe(II) (P
      < 0.05). Cultures of C. neoformans generated between 2 and 160 microM Fe(II) in
      culture supernatant, depending upon the strain and the conditions [the higher
      values were achieved by a constitutive ferric reductase mutant in high
      concentrations of Fe(III)]. We infer that Fe(II) can reduce melanin under
      physiologic conditions; moreover, it binds to melanin and cooperatively increases
      redox buffering. The data support a model for physiologic redox cycling of fungal
      melanin, whereby electrons exported by the yeast to form extracellular Fe(II)
      maintain the reducing capacity of the extracellular redox buffer.

PMID- 9286987
TI  - Biochemical basis for glucose-induced inhibition of malolactic fermentation in
      Leuconostoc oenos.
AB  - The sugar-induced inhibition of malolactic fermentation in cell suspensions of
      Leuconostoc oenos, recently reclassified as Oenococcus oeni (L. M. T. Dicks, F.
      Dellaglio, and M. D. Collins, Int. J. Syst. Bacteriol. 45:395-397, 1995) was
      investigated by in vivo and in vitro nuclear magnetic resonance (NMR)
      spectroscopy and manometric techniques. At 2 mM, glucose inhibited malolactic
      fermentation by 50%, and at 5 mM or higher it caused a maximum inhibitory effect
      of ca. 70%. Galactose, trehalose, maltose, and mannose caused inhibitory effects
      similar to that observed with glucose, but ribose and 2-deoxyglucose did not
      affect the rate of malolactic activity. The addition of fructose or citrate
      completely relieved the glucose-induced inhibition. Glucose was not catabolized
      by permeabilized cells, and inhibition of malolactic fermentation was not
      observed under these conditions. 31P NMR analysis of perchloric acid extracts of
      cells obtained during glucose-malate cometabolism showed high intracellular
      concentrations of glucose-6-phosphate, 6-phosphogluconate, and glycerol-3
      phosphate. Glucose-6-phosphate, 6-phosphogluconate, and NAD(P)H inhibited the
      malolactic activity in permeabilized cells or cell extracts, whereas NADP+ had no
      inhibitory effect. The purified malolactic enzyme was strongly inhibited by NADH,
      whereas all the other above-mentioned metabolites exerted no inhibitory effect,
      showing that NADH was responsible for the inhibition of malolactic activity in
      vivo. The concentration of NADH required to inhibit the activity of the
      malolactic enzyme by 50% was ca. 25 microM. The data provide a coherent
      biochemical basis to understand the glucose-induced inhibition of malolactic
      fermentation in L. oenos.

PMID- 9286985
TI  - Leaderless polypeptides efficiently extracted from whole cells by osmotic shock.
AB  - Three molecular foldases, DsbA, DsbC, and rotamase (ppiA), exhibited the unusual
      property of accumulating in an osmotically sensitive cellular compartment of
      Escherichia coli when their signal sequences were precisely removed by mutation.
      A mammalian protein, interleukin-1 (IL-1) receptor antagonist, behaved in a
      similar fashion in E. coli when its native signal sequence was deleted. These
      leaderless mutants (but not two control proteins overexpressed in the same
      system) were quantitatively extractable from whole cells by a variety of methods
      generally employed in the recovery of periplasmic proteins. A series of
      biochemical and genetic experiments showed that (i) leaderless DsbA (but not the
      wild type) was retained in a nonperiplasmic location; (ii) beta-galactosidase
      fusions to leaderless DsbA (but not to the wild type) exhibited efficient alpha
      complementation; (iii) none of the leaderless mutant proteins were substantially
      associated with cell membranes, even when they were overexpressed in cells; and
      (iv) leaderless DsbA was not transported to an osmotically sensitive compartment
      via a secA- or ftsZ-dependent mechanism. The observation that these proteins
      transit to some privileged cellular location by a previously undescribed
      mechanism(s)--absent their normal mode of (signal sequence-dependent)
      translocation--was unexpected. DsbA, rotamase, and IL-1, whose tertiary
      structures are known, appear to be structurally unrelated proteins. Despite a
      lack of obvious homologies, these proteins apparently have a common mechanism for
      intracellular localization. As this (putative) bacterial mechanism efficiently
      recognizes proteins of mammalian origin, it must be well conserved across
      evolutionary boundaries.

PMID- 9286989
TI  - Structural characterization of the K antigens from Rhizobium fredii USDA257:
      evidence for a common structural motif, with strain-specific variation, in the
      capsular polysaccharides of Rhizobium spp.
AB  - Rhizobium fredii participates in a nitrogen-fixing symbiosis with soybeans, in a
      strain-cultivar-specific interaction, and past studies have shown that the cell
      surface and extracellular polysaccharides of rhizobia function in the infection
      process that leads to symbiosis. The structural analysis of the capsular
      polysaccharides (K antigens) from strain USDA257 was performed in this study. The
      K antigens were extracted from cultured cells with hot phenol-water and purified
      by size exclusion chromatography. We isolated two structurally distinct K
      antigens, both containing a high proportion of 3-deoxy-D-manno-2-octulosonic acid
      (Kdo). The polysaccharides were characterized by matrix-assisted laser desorption
      ionization-time-of-flight-mass spectrometry, nuclear magnetic resonance
      spectrometry, and gas chromatography-mass spectrometry analyses. The primary
      polysaccharide, which constituted about 60% of the K-antigen preparation,
      consisted of repeating units of mannose (Man) and Kdo, [-->)3-beta-D-Manp-(1-->5)
      beta-D-Kdop-(2-->], and a second polysaccharide consisted of 2-O-MeMan and Kdo, [
      ->)3-beta-D-2-O-MeManp-(1-->5)-beta-D-Kdop-(2-->]. These structures are similar
      to yet distinct from those of other strains of R. fredii and R. meliloti, and
      this finding provides further evidence that the K antigens of rhizobia are strain
      specific antigens which are produced within a conserved motif.

PMID- 9286988
TI  - Identification of the fliI and fliJ components of the Caulobacter flagellar type
      III protein secretion system.
AB  - Caulobacter crescentus is motile by virtue of a polar flagellum assembled during
      the predivisional stage of the cell cycle. Three mutant strains in which
      flagellar assembly was blocked at an early stage were isolated. The mutations in
      these strains mapped to an operon of two genes, fliI and fliJ, both of which are
      necessary for motility. fliI encodes a 50-kDa polypeptide whose sequence is
      closely related to that of the Salmonella typhimurium FliI protein, an ATPase
      thought to energize the export of flagellar subunits across the cytoplasmic
      membrane through a type III protein secretion system. fliJ encodes a 16-kDa
      hydrophilic protein of unknown function. Epistasis experiments demonstrated that
      the fliIJ operon is located in class II of the C. crescentus flagellar regulatory
      hierarchy, suggesting that the gene products act at an early stage in flagellar
      assembly. The expression of fliIJ is induced midway through the cell cycle,
      coincident with other class II operons, but the FliI protein remains present
      throughout the cell cycle. Subcellular fractionation showed that FliI is present
      both in the cytoplasm and in association with the membrane. Mutational analysis
      of FliI showed that two highly conserved amino acid residues in a bipartite ATP
      binding motif are necessary for flagellar assembly.

PMID- 9286990
TI  - Attachment of Agrobacterium tumefaciens to carrot cells and Arabidopsis wound
      sites is correlated with the presence of a cell-associated, acidic
      polysaccharide.
AB  - An early step in crown gall tumor formation involves the attachment of
      Agrobacterium tumefaciens to host plant cells. A. tumefaciens C58::A205 (C58
      attR) is a Tn3HoHo1 insertion mutant that was found to be avirulent on
      Bryophyllum daigremontiana and unable to attach to carrot suspension cells. The
      mutation mapped to an open reading frame encoding a putative protein of 247 amino
      acids which has significant homology to transacetylases from many bacteria.
      Biochemical analysis of polysaccharide extracts from wild-type strain C58 and the
      C58::A205 mutant showed that the latter was deficient in the production of a cell
      associated polysaccharide. Anion-exchange chromatography followed by 1H nuclear
      magnetic resonance and gas chromatography-mass spectrometry analyses showed that
      the polysaccharide produced by strain C58 was an acetylated, acidic
      polysaccharide and that the polysaccharide preparation contained three sugars:
      glucose, glucosamine, and an unidentified deoxy-sugar. Application of the
      polysaccharide preparation from strain C58 to carrot suspension cells prior to
      inoculation with the bacteria effectively inhibited attachment of the bacteria to
      the carrot cells, whereas an identical preparation from strain C58::A205 had no
      inhibitory effect and did not contain the acidic polysaccharide. Similarly,
      preincubation of Arabidopsis thaliana root segments with the polysaccharide
      prevented attachment of strain C58 to that plant. This indicates that the acidic
      polysaccharide may play a role in the attachment of A. tumefaciens to host soma
      plant cells.

PMID- 9286992
TI  - Regulation of expression of the Lactobacillus pentosus xylAB operon.
AB  - The xylose cluster of Lactobacillus pentosus consists of five genes, two of
      which, xylAB, form an operon and code for the enzymes involved in the catabolism
      of xylose, while a third encodes a regulatory protein, XylR. By introduction of a
      multicopy plasmid carrying the xyl operator and by disruption of the chromosomal
      xylR gene, it was shown that L. pentosus xylR encodes a repressor. Constitutive
      expression of xylAB in the xylR mutant is repressed by glucose, indicating that
      glucose repression does not require XylR. The xylR mutant displayed a prolonged
      lag phase compared to wild-type bacteria when bacteria were shifted from glucose
      to xylose medium. Differences in the growth rate in xylose medium at different
      stages of growth are not correlated with differences in levels of xylAB
      transcription in L. pentosus wild-type or xylR mutant bacteria but are positively
      correlated in Lactobacillus casei with a plasmid containing xylAB. Glucose
      repression was further investigated with a ccpA mutant. An 875-bp internal
      fragment of the ccpA gene of L. pentosus was isolated by PCR and used to
      construct a ccpA knockout mutant. Transcription analysis of L. pentosus xylA
      showed that CcpA is involved in glucose repression. CcpA was also shown to be
      involved in glucose repression of the alpha-amylase promoter of Lactobacillus
      amylovorus by demonstrating that glucose repression of the chloramphenicol
      acetyltransferase gene under control of the alpha-amylase promoter is strongly
      reduced in the L. pentosus ccpA mutant strain.

PMID- 9286991
TI  - A new type of illegitimate recombination is dependent on restriction and
      homologous interaction.
AB  - Illegitimate (nonhomologous) recombination requires little or no sequence
      homology between recombining DNAs and has been regarded as being a process
      distinct from homologous recombination, which requires a long stretch of homology
      between recombining DNAs. Under special conditions in Escherichia coli, we have
      found a new type of illegitimate recombination that requires an interaction
      between homologous DNA sequences. It was detected when a plasmid that carried 2
      kb-long inverted repeats was subjected to type II restriction in vitro and type I
      (EcoKI) restriction in vivo within a delta rac recBC recG ruvC strain. Removal of
      one of the repeats or its replacement with heterologous DNA resulted in a
      reduction in the level of recombination. The recombining sites themselves shared,
      at most, a few base pairs of homology. Many of the recombination events joined a
      site in one of the repeats with a site in another repeat. In two of the products,
      one of the recombining sites was at the end of one of the repeats. Removal of one
      of the EcoKI sites resulted in decreased recombination. We discuss the
      possibility that some structure made by homologous interaction between the long
      repeats is used by the EcoKI restriction enzyme to promote illegitimate
      recombination. The possible roles and consequences of this type of homologous
      interaction are discussed.

PMID- 9286993
TI  - Mutational characterization of promoter regions recognized by the Salmonella
      dublin virulence plasmid regulatory protein SpvR.
AB  - The virulence plasmid-encoded spv regulon is essential for virulence of
      Salmonella dublin in mice. The spvR gene product belongs to the LysR family of
      transcriptional regulator proteins. SpvR induces the expression of the spvABCD
      operon and positively regulates its own expression. DNase I protection analysis
      with purified SpvR fusion proteins identified SpvR binding sites within the spvA
      and spvR promoters (P. Grob and D. G. Guiney, J. Bacteriol. 178:1813-1820, 1996).
      We have used PCR mutagenesis, combined with functional selection for reduced SpvR
      affinity, to define the DNA elements essential for SpvR binding. For the spvR
      promoter fragment, a screen for reduced expression was also applied. Sequence
      analysis of the resulting mutant fragments reveals that the base pair changes are
      clustered in distinct regions. Determination of the apparent dissociation
      constants of SpvR for the mutant promoters showed that the spvA LysR-type motif
      and the upstream palindromic sequences of both promoters play an important role
      in SpvR recognition.

PMID- 9286994
TI  - DNA bending by the TrpI protein of Pseudomonas aeruginosa.
AB  - TrpI protein, the activator of transcription of the trpBA operon of fluorescent
      pseudomonads, bends the DNA when it forms either of two well-characterized
      complexes with the trpBA regulatory region. In complex 1, with TrpI bound only to
      its strong binding site (site I), the calculated bending angle is 65 to 67
      degrees and the center of bending is in the middle of site I. In complex 2, which
      is required for activation of the trpBA promoter, with TrpI bound both to site I
      and to the weaker site II, the bending angle is increased to 89 to 90 degrees and
      the center of bending is at the site I-site II boundary. Indoleglycerol phosphate
      (InGP), which strongly stimulates formation of complex 2 and is required for
      activation, does not affect the bending angle of either complex. However, a
      mutation (-10C/11C) shown previously to affect activation has a small but
      detectable effect on bending, reducing the calculated bending angle to 83 to 86
      degrees. These results suggest a way that DNA bending and InGP may be important
      for activation.

PMID- 9286995
TI  - Purified outer membranes of Serpulina hyodysenteriae contain cholesterol.
AB  - We have isolated outer and inner membranes of Serpulina hyodysenteriae by using
      discontinuous sucrose density gradients. The outer and inner membrane fractions
      contained less than 1 and 2%, respectively, of the total NADH oxidase activity
      (soluble marker) in the cell lysate. Various membrane markers including
      lipooligosaccharide (LOS), the 16-kDa outer membrane lipoprotein (SmpA), and the
      C subunit of the F1F0 ATPase indicated that the lowest-density membrane fraction
      contained outer membranes while the high-density membrane fraction contained
      inner membranes and that both are essentially free of contamination by the
      periplasmic flagella, a major contaminant of membranes isolated by other
      techniques. The outer membrane fractions (rho = 1.10 g/cm3) contained 0.25 mg of
      protein/mg (dry weight), while the inner membrane samples (rho = 1.16 g/cm3)
      contained significantly more protein (0.55 mg of protein/mg [dry weight]). Lipid
      analysis revealed that the purified outer membranes contained cholesterol as a
      major component of the membrane lipids. Treatment of intact S. hyodysenteriae
      with different concentrations of digitonin, a steroid glycoside that interacts
      with cholesterol, indicated that the outer membrane could be selectively removed
      at concentrations as low as 0.125%.

PMID- 9286996
TI  - Differential levels of specific cytochrome c biogenesis proteins in response to
      oxygen: analysis of the ccl operon in Rhodobacter capsulatus.
AB  - The photosynthetic bacterium Rhodobacter capsulatus synthesizes c-type
      cytochromes under a variety of growth conditions. For example, under aerobic
      growth, c-type cytochromes are synthesized as part of an electron transport
      pathway, using oxygen as the terminal electron acceptor. Anaerobically in the
      light, R. capsulatus requires cytochrome bc1 and other c-type cytochromes for the
      photosynthetic electron transport pathway. It is shown here that the ccl1 and
      ccl2 genes of R. capsulatus are required for the synthesis of all c-type
      cytochromes, including the cytochrome c' protein of unknown function but of
      structural similarity to cytochrome b562. Polar and nonpolar mutations
      constructed in each gene demonstrated that the ccl12 genes form an operon.
      Expression of the ccl12 genes was examined by using lacZ and phoA fusions as
      translational reporters. Primer extension analysis was used to determine
      transcriptional control and the start site of the ccl12 promoter. Finally,
      antiserum to the Ccl2 protein was used to quantitate levels of Ccl2 under six
      different growth conditions. The Ccl2 protein is present at 20-fold-higher levels
      under conditions where oxygen is present. In contrast, other cytochromes c
      biogenesis proteins, HelA and HelX, previously shown to be part of an helABCDX
      operon, are at relatively similar levels under these six growth conditions. This
      discovery is discussed in terms of the physiology and evolution of cytochromes c
      biogenesis, with particular attention to oxidative environments.

PMID- 9286997
TI  - In vitro phosphorylation study of the arc two-component signal transduction
      system of Escherichia coli.
AB  - The ArcB and ArcA proteins constitute a two-component signal transduction system
      that plays a broad role in transcriptional regulation. Under anoxic or
      environmentally reducing conditions, the sensor kinase (ArcB) is stimulated to
      autophosphorylate at the expense of ATP and subsequently transphosphorylates the
      response regulator (ArcA). ArcB is a complex, membrane-bound protein comprising
      at least three cytoplasmic domains, an N-terminal transmitter domain with a
      conserved His292 residue (H1), a central receiver domain with a conserved Asp576
      residue (D1), and a C-terminal alternative transmitter domain with a conserved
      His717 residue (H2). To study the phosphoryl transfer pathways of the Arc system,
      we prepared the following His-tagged proteins: H1, D1, H2, H1-D1, D1-H2, H1-D1
      H2, and ArcA. Incubations of various combinations of Arc proteins with [gamma
      32P]ATP indicated that H1, but not D1 or H2, catalyzes autophosphorylation; that
      H1-P transfers the phosphoryl group to D1 much more rapidly than to ArcA; and
      that D1 accelerates the transphosphorylation of H2. Finally, ArcA is
      phosphorylated much more rapidly by H2-P than by H1-P. Available data are
      consistent with a signal transduction model in which (i) reception of a membrane
      signal(s) triggers autophosphorylation of H1 at His292, (ii) the phosphoryl group
      can migrate to D1 at Asp576 and subsequently to H2 at His717, and (iii) ArcA
      receives the phosphoryl group from either His292 or His717, the relative
      contribution of which is regulated by cytosolic effectors.

PMID- 9286998
TI  - Isolation, analysis, and expression of two genes from Thermoanaerobacterium sp.
      strain JW/SL YS485: a beta-xylosidase and a novel acetyl xylan esterase with
      cephalosporin C deacetylase activity.
AB  - The genes encoding acetyl xylan esterase 1 (axe1) and a beta-xylosidase (xylB)
      have been cloned and sequenced from Thermoanaerobacterium sp. strain JW/SL YS485.
      axe1 is located 22 nucleotides 3' of the xylB sequence. The identity of axe1 was
      confirmed by comparison of the deduced amino acid sequence to peptide sequence
      analysis data from purified acetyl xylan esterase 1. The xylB gene was identified
      by expression cloning and by sequence homology to known beta-xylosidases.
      Plasmids which independently expressed either acetyl xylan esterase 1 (pAct1BK)
      or beta-xylosidase (pXylo-1.1) were constructed in Escherichia coli. Plasmid
      pXylAct-1 contained both genes joined at a unique EcoRI site and expressed both
      activities. Substrate specificity, pH, and temperature optima were determined for
      partially purified recombinant acetyl xylan esterase 1 and for crude recombinant
      beta-xylosidase. Similarity searches showed that the axe1 and xylB genes were
      homologs of the ORF-1 and xynB genes, respectively, isolated from
      Thermoanaerobacterium saccharolyticum. Although the deduced sequence of the axe1
      product had no significant amino acid sequence similarity to any reported acetyl
      xylan esterase sequence, it did have strong similarity to cephalosporin C
      deacetylase from Bacillus subtilis. Recombinant acetyl xylan esterase 1 was found
      to have thermostable deacetylase activity towards a number of acetylated
      substrates, including cephalosporin C and 7-aminocephalosporanic acid.

PMID- 9286999
TI  - The genes for butanol and acetone formation in Clostridium acetobutylicum ATCC
      824 reside on a large plasmid whose loss leads to degeneration of the strain.
AB  - Degeneration is the process whereby Clostridium acetobutylicum ATCC 824 loses the
      capacity to produce acetone and butanol after repeated vegetative transfers or in
      continuous culture. Two degenerate mutants (M5 and DG1) of C. acetobutylicum ATCC
      824 do not contain the four genes (ctfA, ctfB, adc, and aad) for acetone and
      butanol formation. Strain ATCC 824 contains a 210-kb plasmid (pSOL1) which is
      absent in M5 and DG1. pSOL1 carries the four acetone and butanol formation genes.
      A restriction map of pSOL1 was constructed by using ApaI, SmaI, SstII, and NarI
      digestions. M5 and DG1 could be complemented for acetone and butanol formation by
      expressing the corresponding genes (ctfA, ctfB, and adc for acetone; aad for
      butanol) on the plasmid. Degeneration of this strain thus appears to be the
      result of pSOL1 loss.

PMID- 9287001
TI  - Mutation of a single MalK subunit severely impairs maltose transport activity in
      Escherichia coli.
AB  - The maltose transport system of Escherichia coli, a member of the ABC transport
      superfamily of proteins, consists of a periplasmic maltose binding protein and a
      membrane-associated translocation complex that contains two copies of the ATP
      binding protein MalK. To examine the need for two nucleotide-binding domains in
      this transport complex, one of the two MalK subunits was inactivated by site
      directed mutagenesis. Complexes with mutations in a single subunit were obtained
      by attaching a polyhistidine tag to the mutagenized version of MalK and by
      coexpressing both wild-type MalK and mutant (His)6MalK in the same cell. Hybrid
      complexes containing one mutant (His)6MalK subunit and one wild-type MalK subunit
      were separated from those containing two mutant (His)6MalK proteins based on
      differential affinities for a metal chelate column. Purified transport complexes
      were reconstituted into proteoliposome vesicles and assayed for maltose transport
      and ATPase activities. When a conserved lysine residue at position 42 that is
      involved in ATP binding was replaced with asparagine in both MalK subunits,
      maltose transport and ATPase activities were reduced to 1% of those of the wild
      type. When the mutation was present in only one of the two subunits, the complex
      had 6% of the wild-type activities. Replacement of a conserved histidine residue
      at position 192 in MalK with arginine generated similar results. It is clear from
      these results that two functional MalK proteins are required for transport
      activity and that the two nucleotide-binding domains do not function
      independently to catalyze transport.

PMID- 9287000
TI  - An lrp-like gene of Bacillus subtilis involved in branched-chain amino acid
      transport.
AB  - The azlB locus of Bacillus subtilis was defined previously by a mutation
      conferring resistance to a leucine analog, 4-azaleucine (J. B. Ward, Jr., and S.
      A. Zahler, J. Bacteriol. 116:727-735, 1973). In this report, azlB is shown to be
      the first gene of an operon apparently involved in branched-chain amino acid
      transport. The product of the azlB gene is an Lrp-like protein that negatively
      regulates expression of the azlBCDEF operon. Resistance to 4-azaleucine in azlB
      mutants is due to overproduction of AzlC and AzlD, two novel hydrophobic
      proteins.

PMID- 9287002
TI  - Outer membrane localization of murein hydrolases: MltA, a third lipoprotein lytic
      transglycosylase in Escherichia coli.
AB  - Lytic transglycosylases are a unique lysozyme-like class of murein hydrolases
      believed to be important for growth of Escherichia coli. A membrane-bound lytic
      transglycosylase with an apparent molecular mass of 38 kDa, which was designated
      Mlt38, has previously been purified and characterized (A. Ursinus and J.-V.
      Holtje, J. Bacteriol. 176:338-343, 1994). On the basis of four tryptic peptides,
      the gene mltA was mapped at 63 min on the chromosomal map of E. coli K-12 and
      cloned by reverse genetics. The open reading frame was found to contain a typical
      lipoprotein consensus sequence, and the lipoprotein nature of the gene product
      was demonstrated by [3H]palmitate labeling. On the basis of the distribution of
      MltA in membrane fractions obtained by sucrose gradient centrifugation, a
      localization in the outer membrane is indicated. Overexpression of MltA at 30
      degrees C, the optimal temperature for enzyme activity, but not at 37 degrees C
      results in the formation of spheroplasts. Not only a deletion mutant in mltA, but
      also double mutants in mltA and one of the two other well-characterized lytic
      transglycosylases (either sltY or mltB), as well as a triple mutant in all three
      enzymes, showed no obvious phenotype. However, dramatic changes in the structure
      of the murein sacculus indicate that lytic transglycosylases are involved in
      maturation of the murein sacculus.

PMID- 9287003
TI  - Osmotically induced response in representatives of halophilic prokaryotes: the
      bacterium Halomonas elongata and the archaeon Haloferax volcanii.
AB  - Haloferax volcanii and Halomonas elongata have been selected as representatives
      of halophilic Archaea and Bacteria, respectively, to analyze the responses to
      various osmolarities at the protein synthesis level. We have identified a set of
      high-salt-related proteins (39, 24, 20, and 15.5 kDa in H. elongata; 70, 68, 48,
      and 16 kDa in H. volcanii) whose synthesis rates increased with increasing
      salinities. A different set of proteins (60, 42, 15, and 6 kDa for H. elongata;
      63, 44, 34, 18, 17, and 6 kDa for H. volcanii), some unique for low salinities,
      was induced under low-salt conditions. For both organisms, and especially for the
      haloarchaeon, adaptation to low-salt conditions involved a stronger and more
      specific response than adaptation to high-salt conditions, indicating that unique
      mechanisms may have evolved for low-salinity adaptation. In the case of H.
      volcanii, proteins with a typical transient response to osmotic shock, induced by
      both hypo- and hyperosmotic conditions, probably corresponding to described heat
      shock proteins and showing the characteristics of general stress proteins, have
      also been identified. Cell recovery after a shift to low salinities was immediate
      in both organisms. In contrast, adaptation to higher salinities in both cases
      involved a lag period during which growth and general protein synthesis were
      halted, although the high-salt-related proteins were induced rapidly. In H.
      volcanii, this lag period corresponded exactly to the time needed for cells to
      accumulate adequate intracellular potassium concentrations, while extrusion of
      potassium after the down-shift was immediate. Thus, reaching osmotic balance must
      be the main limiting factor for recovery of cell functions after the variation in
      salinity.

PMID- 9287004
TI  - TRAP transporters: a new family of periplasmic solute transport systems encoded
      by the dctPQM genes of Rhodobacter capsulatus and by homologs in diverse gram
      negative bacteria.
AB  - The dct locus of Rhodobacter capsulatus encodes a high-affinity transport system
      for the C4-dicarboxylates malate, succinate, and fumarate. The nucleotide
      sequence of the region downstream of the previously sequenced dctP gene (encoding
      a periplasmic C4-dicarboxylate-binding protein) was determined. Two open reading
      frames (ORFs) of 681 bp (dctQ) and 1,320 bp (dctM) were identified as additional
      dct genes by insertional mutagenesis and complementation studies. DctQ (24,763
      Da) and DctM (46,827 Da) had hydropathic profiles consistent with the presence of
      4 and 12 potential transmembrane segments, respectively, and were localized in
      the cytoplasmic membrane fraction after heterologous expression of the dctQM ORFs
      in Escherichia coli. DctP, DctQ, and DctM were found to be unrelated to known
      transport proteins in the ABC (ATP-binding cassette) superfamily but were shown
      to be homologous with the products of previously unidentified ORFs in a number of
      gram-negative bacteria, including Bordetella pertussis, E. coli, Salmonella
      typhimurium, Haemophilus influenzae, and Synechocystis sp. strain PCC6803. An
      additional ORF (rypA) downstream of dctM encodes a protein with sequence
      similarity to eukaryotic protein-tyrosine phosphatases, but interposon
      mutagenesis of this ORF did not result in a Dct- phenotype. Complementation of a
      Rhizobium meliloti dctABD deletion mutant by heterologous expression of the
      dctPQM genes from R. capsulatus demonstrated that no additional structural genes
      were required to form a functional transport system. Transport via the Dct system
      was vanadate insensitive, and in uncoupler titrations with intact cells, the
      decrease in the rate of succinate transport correlated closely with the fall in
      membrane potential but not with the cellular ATP concentration, implying that the
      proton motive force, rather than ATP hydrolysis, drives uptake. It is concluded
      that the R. capsulatus Dct system is a new type of periplasmic secondary
      transporter and that similar, hitherto-unrecognized systems are widespread in
      gram-negative bacteria. The name TRAP (for tripartite ATP-independent
      periplasmic) transporters is proposed for this new group.

PMID- 9287007
TI  - Environmental signals triggering methylenomycin production by Streptomyces
      coelicolor A3(2).
AB  - Methylenomycin production by Streptomyces coelicolor A3(2) may be triggered by
      either of two environmental signals: alanine growth-rate-limiting conditions
      and/or an acidic pH shock. The production of this SCP1-encoded antibiotic was
      studied by using batch and chemostat cultures. Batch cultures indicated a role
      for both nutritional status and culture pH in its regulation. Steady-state
      methylenomycin production and transcription of an mmy gene under alanine but not
      glucose growth-rate-limiting conditions was demonstrated in chemostat culture.
      Transient mmy expression and methylenomycin production occurred following an
      acidic pH shock. This stimulation of methylenomycin production occurred
      independently of the nutritional status of the growth environment. Antibiotic
      production was partially suppressed under alanine compared with glucose growth
      rate-limiting conditions following the acidic pH shock. A low specific growth
      rate was a prerequisite for both steady-state and transient production of
      methylenomycin.

PMID- 9287005
TI  - Expression of the Bacillus subtilis ureABC operon is controlled by multiple
      regulatory factors including CodY, GlnR, TnrA, and Spo0H.
AB  - Expression of urease, which is encoded by the ureABC operon, is regulated in
      response to nitrogen availability in Bacillus subtilis. Three ureABC promoters
      were identified in primer extension experiments and by examination of beta
      galactosidase expression from ure-lacZ fusions. P1, a low-level constitutive
      promoter, lies immediately upstream of ureA. The P2 promoter is transcribed by
      the E sigmaH form of RNA polymerase and initiates transcription 270 bp upstream
      of the ureA start codon. The transcriptional start site for the sigmaA-dependent
      P3 promoter is located 839 bp upstream of the ureA start codon. To identify
      transcription factors that control ureABC expression, regulation of the P2 and P3
      promoters was examined in wild-type and mutant strains. During rapid growth in
      minimal medium containing glucose and amino acids, CodY represses expression of
      the P2 and P3 promoters 30- and 60-fold, respectively. TnrA activates expression
      of the P3 promoter 10-fold in nitrogen-limited cells, while GlnR represses
      transcription from the P3 promoter 55-fold during growth on excess nitrogen.
      Expression of the ureABC operon increases 10-fold at the end of exponential
      growth in nutrient sporulation medium. This elevation in expression results from
      the relief of CodY-mediated repression during exponential growth and increased
      sigmaH-dependent transcription during stationary phase.

PMID- 9287006
TI  - A gene coding for a putative sigma 54 activator is developmentally regulated in
      Caulobacter crescentus.
AB  - In Caulobacter crescentus, the alternative sigma factor sigma54 plays an
      important role in the expression of late flagellar genes. Sigma54-dependent genes
      are temporally and spatially controlled, being expressed only in the swarmer pole
      of the predivisional cell. The only sigma54 activator described so far is the
      FlbD protein, which is involved in activation of the class III and IV flagellar
      genes and repression of the fliF promoter. To identify new roles for sigma54 in
      the metabolism and differentiation of C. crescentus, we cloned and characterized
      a gene encoding a putative sigma54 activator, named tacA. The deduced amino acid
      sequence from tacA has high similarity to the proteins from the NtrC family of
      transcriptional activators, including the aspartate residues that are
      phosphorylated by histidine kinases in other activators. The promoter region of
      the tacA gene contains a conserved sequence element present in the promoters of
      class II flagellar genes, and tacA shows a temporal pattern of expression similar
      to the patterns of these genes. We constructed an insertional mutant that is
      disrupted in tacA (strain SP2016), and an analysis of this strain showed that it
      has all polar structures, such as pili, stalk, and flagellum, and displays a
      motile phenotype, indicating that tacA is not involved in the flagellar
      biogenesis pathway. However, this strain has a high percentage of filamentous
      cells and shows a clear-plaque phenotype when infected with phage phiCb5. These
      results suggest that the TacA protein could mediate the effect of sigma54 on a
      different pathway in C. crescentus.

PMID- 9287008
TI  - Metals control activity and expression of the heme biosynthesis enzyme delta
      aminolevulinic acid dehydratase in Bradyrhizobium japonicum.
AB  - The heme biosynthesis enzyme delta-aminolevulinic acid dehydratase (ALAD)
      requires magnesium or zinc for activity, depending on the organism, and the heme
      moiety contains iron. Thus, metals are important for heme formation in at least
      two different ways. Bradyrhizobium japonicum ALAD* is an engineered derivative of
      wild-type ALAD that requires Zn2+ for activity rather than Mg2+ (S. Chauhan and
      M. R. O'Brian, J. Biol. Chem. 270:19823-19827, 1995). The pH optimum for ALAD*
      activity was over 3.5 units lower than for that of the wild-type enzyme, and
      ALAD* activity was inhibited by lead and cadmium, as reported for the zinc
      containing dehydratases of animals. In addition, ALAD* was significantly more
      thermostable than ALAD; the temperature optima are 50 and 37 degrees C,
      respectively. These observations strongly suggest that the metal contributes to
      both catalysis and structure, and this conclusion may be extrapolated to ALADs in
      general. Although iron did not affect the activity of the preformed protein,
      enzyme assays and immunoblot analysis demonstrated that the iron concentration in
      which the cells were grown had a strong positive effect on ALAD activity and the
      protein level. RNase protection analysis showed that the transcript quantity of
      hemB, the gene encoding ALAD, was iron dependent; thus, iron regulates hemB at
      the mRNA level. Induction of hemB mRNA in response to iron was rapid, suggesting
      that the factor(s) needed to mediate iron control was present in iron-limited
      cells and did not need to be synthesized de novo. ALAD protein levels and enzyme
      activities were similar in cells of the wild type and a heme-defective strain,
      indicating that control by iron is not an indirect effect of the cellular heme
      status. We conclude that the heme biosynthetic pathway is coordinated with
      cellular iron levels and that this control may prevent the accumulation of toxic
      porphyrin intermediates.

PMID- 9287009
TI  - Mutation of the htrB gene in a virulent Salmonella typhimurium strain by
      intergeneric transduction: strain construction and phenotypic characterization.
AB  - The htrB gene product of Haemophilus influenzae contributes to the toxicity of
      the lipooligosaccharide. The htrB gene encodes a 2-keto-3-deoxyoctulosonic acid
      dependent acyltransferase which is responsible for myristic acid substitutions at
      the hydroxy moiety of lipid A beta-hydroxymyristic acid. Mass spectroscopic
      analysis has demonstrated that lipid A from an H. influenzae htrB mutant is
      predominantly tetraacyl and similar in structure to lipid IV(A), which has been
      shown to be nontoxic in animal models. We sought to construct a Salmonella
      typhimurium htrB mutant in order to investigate the contribution of htrB to
      virulence in a well-defined murine typhoid model of animal pathogenesis. To this
      end, an r- m+ galE mutS recD strain of S. typhimurium was constructed (MGS-7) and
      used in inter- and intrastrain transduction experiments with both coliphage P1
      and Salmonella phage P22. The Escherichia coli htrB gene containing a mini-Tn10
      insertion was transduced from E. coli MLK217 into S. typhimurium MGS-7 via phage
      P1 and subsequently via phage P22 into the virulent Salmonella strain SL1344. All
      S. typhimurium transductants showed phenotypes similar to those described for the
      E. coli htrB mutant. Mass spectrometric analysis of the crude lipid A fraction
      from the lipopolysaccharide of the S. typhimurium htrB mutant strain showed that
      for the dominant hexaacyl form, a lauric acid moiety was lost at one position on
      the lipid A and a palmitic acid moiety was added at another position; for the
      less abundant heptaacyl species, the lauric acid was replaced with palmitoleic
      acid.

PMID- 9287010
TI  - SpoVM, a small protein essential to development in Bacillus subtilis, interacts
      with the ATP-dependent protease FtsH.
AB  - The spoVM gene encodes a 26-amino-acid polypeptide that is essential for spore
      formation in Bacillus subtilis. A transposon insertion within the spoVM open
      reading frame has been shown to encode a chimeric protein which is biologically
      inactive and produces a phenotype identical to that of a deletion and insertion
      mutation. A genetic approach was used to identify possible interacting proteins,
      and the membrane-bound FtsH protease was identified. Mutations in ftsH suppressed
      the sporulation defect of certain spoVM mutants but not others. However,
      production of the mother cell sigma factors, sigmaE and sigmaK, was abnormal in
      the suppressed strains, and mutations in either spoVM or ftsH alone impaired
      sigma factor production and sporulation gene expression. Using FtsH purified from
      Escherichia coli, we demonstrated that in vitro (i) SpoVM inhibits FtsH protease
      activity and (ii) SpoVM is a substrate for the FtsH protease. We propose that
      during sporulation, SpoVM serves as a competitive inhibitor of FtsH activity.
      This interaction appears to be important for completion of the prespore
      engulfment step of sporulation, based on the phenotype of certain spoVM ftsH
      double mutants.

PMID- 9287012
TI  - Analysis of the interaction of FtsZ with itself, GTP, and FtsA.
AB  - The interaction of FtsZ with itself, GTP, and FtsA was examined by analyzing the
      sensitivity of FtsZ to proteolysis and by using the yeast two-hybrid system. The
      N-terminal conserved domain consisting of 320 amino acids bound GTP, and a
      central region of FtsZ, encompassing slightly more than half of the protein, was
      cross-linked to GTP. Site-directed mutagenesis revealed that none of six highly
      conserved aspartic acid and asparagine residues were required for GTP binding.
      These results indicate that the specificity determinants for GTP binding are
      different than those for the GTPase superfamily. The N-terminal conserved domain
      of FtsZ contained a site for self-interaction that is conserved between FtsZ
      proteins from distantly related bacterial species. FtsZ320, which was truncated
      at the end of the conserved domain, was a potent inhibitor of division although
      it expressed normal GTPase activity and could polymerize. FtsZ was also found to
      interact directly with FtsA, and this interaction could also be observed between
      these proteins from distantly related bacterial species.

PMID- 9287011
TI  - A fragment liberated from the Escherichia coli CheA kinase that blocks
      stimulatory, but not inhibitory, chemoreceptor signaling.
AB  - CheA, a cytoplasmic histidine autokinase, in conjunction with the CheW coupling
      protein, forms stable ternary complexes with the cytoplasmic signaling domains of
      transmembrane chemoreceptors. These signaling complexes induce chemotactic
      movements by stimulating or inhibiting CheA autophosphorylation activity in
      response to chemoeffector stimuli. To explore the mechanisms of CheA control by
      chemoreceptor signaling complexes, we examined the ability of various CheA
      fragments to interfere with receptor coupling control of CheA. CheA[250-654], a
      fragment carrying the catalytic domain and an adjacent C-terminal segment
      previously implicated in stimulatory control of CheA activity, interfered with
      the production of clockwise flagellar rotation and with chemotactic ability in
      wild-type cells. Epistasis tests indicated that CheA[250-654] blocked clockwise
      rotation by disrupting stimulatory coupling of CheA to receptors. In vitro
      coupling assays confirmed that a stoichiometric excess of CheA[250-654] fragments
      could exclude CheA from stimulatory receptor complexes, most likely by competing
      for CheW binding. However, CheA[250-654] fragments, even in vast excess, did not
      block receptor-mediated inhibition of CheA, suggesting that CheA[250-654] lacks
      an inhibitory contact site present in native CheA. This inhibitory target is most
      likely in the N-terminal P1 domain, which contains His-48, the site of
      autophosphorylation. These findings suggest a simple allosteric model of CheA
      control by ternary signaling complexes in which the receptor signaling domain
      conformationally regulates the interaction between the substrate and catalytic
      domains of CheA.

PMID- 9287014
TI  - Lactose carrier mutants of Escherichia coli with changes in sugar recognition
      (lactose versus melibiose).
AB  - The purpose of this research was to identify amino acid residues that mediate
      substrate recognition in the lactose carrier of Escherichia coli. The lactose
      carrier transports the alpha-galactoside sugar melibiose as well as the beta
      galactoside sugar lactose. Mutants from cells containing the lac genes on an F
      factor were selected by the ability to grow on succinate in the presence of the
      toxic galactoside beta-thio-o-nitrophenylgalactoside. Mutants that grew on
      melibiose minimal plates but failed to grow on lactose minimal plates were
      picked. In sugar transport assays, mutant cells showed the striking result of
      having low levels of lactose downhill transport but high levels of melibiose
      downhill transport. Accumulation (uphill) of melibiose was completely defective
      in all of the mutants. Kinetic analysis of melibiose transport in the mutants
      showed either no change or a greater than normal apparent affinity for melibiose.
      PCR was used to amplify the lacY DNA of each mutant, which was then sequenced by
      the Sanger method. The following six mutations were found in the lacY structural
      genes of individual mutants: Tyr-26-->Asp, Phe-27-->Tyr, Phe-29-->Leu, Asp-240-
      >Val, Leu-321-->Gln, and His-322-->Tyr. We conclude from these experiments that
      Tyr-26, Phe-27, Phe-29 (helix 1), Asp-240 (helix 7), Leu-321, and His-322 (helix
      10) either directly or indirectly mediate sugar recognition in the lactose
      carrier of E. coli.

PMID- 9287013
TI  - A succinate dehydrogenase with novel structure and properties from the
      hyperthermophilic archaeon Sulfolobus acidocaldarius: genetic and biophysical
      characterization.
AB  - The sdh operon of Sulfolobus acidocaldarius DSM 639 is composed of four genes
      coding for the 63.1-kDa flavoprotein (SdhA), the 36.5-kDa iron-sulfur protein
      (SdhB), and the 32.1-kDa SdhC and 14.1-kDa SdhD subunits. The four structural
      genes of the sdhABCD operon are transcribed into one polycistronic mRNA of 4.2
      kb, and the transcription start was determined by the primer extension method to
      correspond with the first base of the ATG start codon of the sdhA gene. The S.
      acidocaldarius SdhA and SdhB subunits show characteristic sequence similarities
      to the succinate dehydrogenases and fumarate reductases of other organisms, while
      the SdhC and SdhD subunits, thought to form the membrane-anchoring domain, lack
      typical transmembrane alpha-helical regions present in all other
      succinate:quinone reductases (SQRs) and quinol:ifumarate reductases (QFRs) so far
      examined. Moreover, the SdhC subunit reveals remarkable 30% sequence similarity
      to the heterodisulfide reductase B subunit of Methanobacterium
      thermoautotrophicum and Methanococcus jannaschii, containing all 10 conserved
      cysteine residues. Electron paramagnetic resonance (EPR) spectroscopic studies of
      the purified enzyme as well as of membranes revealed the presence of typical S1
      [2Fe2S] and S2 [4Fe4S] clusters, congruent with the deduced amino acid sequences.
      In contrast, EPR signals for a typical S3 [3Fe4S] cluster were not detected.
      However, EPR data together with sequence information implicate the existence of a
      second [4Fe4S] cluster in S. acidocaldarius rather than a typical [3Fe4S]
      cluster. These results and the fact that the S. acidocaldarius succinate
      dehydrogenase complex reveals only poor activity with caldariella quinone clearly
      suggest a unique structure for the SQR of S. acidocaldarius, possibly involving
      an electron transport pathway from the enzyme complex into the respiratory chain
      different from those for known SQRs and QFRs.

PMID- 9287016
TI  - Division pattern of a round mutant of Escherichia coli.
AB  - A round mutant of Escherichia coli, when grown in Methocel medium, forms chains
      of cells and does not form tetrads. This implies that successive division planes
      of the round mutant are parallel rather than perpendicular. These results differ
      from a previous proposal that division planes in this round mutant are
      perpendicular to the prior division plane (W. D. Donachie, S. Addinall, and K.
      Begg, Bioessays 17:569-576, 1995).

PMID- 9287015
TI  - A transcriptional activator, FleQ, regulates mucin adhesion and flagellar gene
      expression in Pseudomonas aeruginosa in a cascade manner.
AB  - Previous work has demonstrated that fleR, the gene for a transcriptional
      activator belonging to the NtrC subfamily of response regulators, is involved in
      the regulation of mucin adhesion and flagellar expression by Pseudomonas
      aeruginosa. This report describes the identification and characterization of
      fleQ, the gene for another transcriptional regulator which also regulates mucin
      adhesion and motility in this organism. The complete nucleotide sequence of the
      fleQ gene was determined on both DNA strands, and an open reading frame (ORF)
      consisting of 1,493 nucleotides was identified. This ORF coded for a gene product
      of predicted molecular weight, as confirmed by the overexpression of the fleQ
      gene as a fusion protein under an inducible promoter. The fleQ gene is flanked by
      a flagellar operon, fliDSorf126, at the 5' end and the fleSR operon on the 3'
      end. FleQ also had striking homology to a number of proteins belonging to the
      NtrC subfamily of response regulators, which work in concert with the alternate
      sigma factor RpoN (sigma54) to activate transcription. However, FleQ lacks the
      residues corresponding to Asp-54 and Lys-104 of the NtrC protein which are
      conserved in most of the members belonging to this subfamily of regulators. In
      addition, unlike some of the other transcriptional activators of this group, FleQ
      does not appear to have a cognate sensor kinase. A chromosomal insertional
      mutation in the fleQ gene abolished mucin adhesion and motility of P. aeruginosa
      PAK and PAK-NP. Both of these functions were regained by providing the complete
      fleQ gene on a multicopy plasmid. The location of fleQ immediately upstream of
      the fleSR operon, which is also necessary for the same process, suggested that
      these regulators may interact in some way. We therefore examined the regulation
      of the fleSR operon by fleQ and vice versa. Promoter fusion experiments showed
      that the fleSR operon was regulated by RpoN and FleQ. On the other hand, the fleQ
      promoter was independent of RpoN and FleR. FleQ, thus, adds another level of
      regulation to motility and adhesion in P. aeruginosa, above that of fleSR. We
      therefore propose the existence of a regulatory cascade which consists of at
      least two transcriptional regulators, FleQ and FleR, in the control of motility
      and adhesion in P. aeruginosa.

PMID- 9287017
TI  - Negative feedback from a Proteus class II flagellum export defect to the flhDC
      master operon controlling cell division and flagellum assembly.
AB  - The Proteus mirabilis flagellum class I flhDC operon was isolated, and its
      transcript was shown to originate from a sigma70 promoter 244 bp 5' of flhD and
      29 bp 3' of a putative cyclic AMP receptor protein-binding site. Expression of
      this regulatory master operon increased strongly as cells differentiated into
      elongated hyperflagellated swarm filaments, and cell populations artificially
      overexpressing flhDC migrated sooner and faster. A class II flhA transposon
      mutant was reduced in flagellum class III gene expression, as would be expected
      from the FlgM anti-sigma28 accumulation demonstrated in Salmonella typhimurium,
      but was unexpectedly also reduced in cell elongation. Here, we show that levels
      of flhDC transcript were ca. 10-fold lower in this flagellum export mutant,
      indicating that in cells defective in flagellum assembly, there is additional
      negative feedback via flhDC. In support of this view, artificial overexpression
      of flhDC in the flhA mutant restored elongation but not class III flagellum gene
      transcription.

PMID- 9287018
TI  - Characterization of cspB, a cold-shock-inducible gene from Lactococcus lactis,
      and evidence for a family of genes homologous to the Escherichia coli cspA major
      cold shock gene.
AB  - Upon temperature downshift, the major cold shock protein CspA is highly induced
      in Escherichia coli. This protein being conserved in other bacteria, we used a
      PCR-based approach with a pair of degenerate primers derived from highly
      conserved regions of the CspA-related proteins to evidence the presence of at
      least three related genes in Lactococcus lactis. One of them, cspB, was cloned
      and sequenced. It encodes a 66-residue protein which possesses 60% sequence
      identity with E. coli CspA. Following a cold shock from 30 to 15 degrees C, the
      level of the cspB mRNA transcript increased, as shown by Northern blot
      hybridization. In addition, induction of cspB-directed beta-galactosidase
      activity was observed. These results indicate that the L. lactis cspB gene is
      cold shock inducible.

PMID- 9287019
TI  - GDH3 encodes a glutamate dehydrogenase isozyme, a previously unrecognized route
      for glutamate biosynthesis in Saccharomyces cerevisiae.
AB  - It has been considered that the yeast Saccharomyces cerevisiae, like many other
      microorganisms, synthesizes glutamate through the action of NADP+-glutamate
      dehydrogenase (NADP+-GDH), encoded by GDH1, or through the combined action of
      glutamine synthetase and glutamate synthase (GOGAT), encoded by GLN1 and GLT1,
      respectively. A double mutant of S. cerevisiae lacking NADP+-GDH and GOGAT
      activities was constructed. This strain was able to grow on ammonium as the sole
      nitrogen source and thus to synthesize glutamate through an alternative pathway.
      A computer search for similarities between the GDH1 nucleotide sequence and the
      complete yeast genome was carried out. In addition to identifying its cognate
      sequence at chromosome XIV, the search found that GDH1 showed high identity with
      a previously recognized open reading frame (GDH3) of chromosome I. Triple mutants
      impaired in GDH1, GLT1, and GDH3 were obtained. These were strict glutamate
      auxotrophs. Our results indicate that GDH3 plays a significant physiological
      role, providing glutamate when GDH1 and GLT1 are impaired. This is the first
      example of a microorganism possessing three pathways for glutamate biosynthesis.

PMID- 9287021
TI  - Cell cycle regulation of flagellar genes.
AB  - The expression of the flagellar master operon, flhDC, peaked in the middle of
      three consecutive cell cycles. The level of expression was lowest at the time of
      cell division. The expression of the second-level operon, flhB, peaked at cell
      division. The swimming speed of individual cells was also highest at the time of
      cell division.

PMID- 9287020
TI  - Oxygen-dependent growth of the obligate anaerobe Desulfovibrio vulgaris
      Hildenborough.
AB  - Desulfovibrio vulgaris Hildenborough, a sulfate-reducing bacterium classified as
      an obligate anaerobe, swam to a preferred oxygen concentration of 0.02 to 0.04%
      (0.24 to 0.48 microM), a level which also supported growth. Oxygen concentrations
      of 0.08% and higher arrested growth. We propose that in zones of transition from
      an oxic to an anoxic environment, D. vulgaris protects anoxic microenvironments
      from intrusion of oxygen.

PMID- 9287022
TI  - Activation of the Bacillus subtilis spoIIG promoter requires interaction of Spo0A
      and the sigma subunit of RNA polymerase.
AB  - Bacillus subtilis Spo0A activates transcription from both sigmaA- and sigmaH
      dependent promoters. Baldus et al. (2) identified two amino acid substitutions in
      the carboxyl terminus of sigmaA, K356E and H359R, that specifically impaired
      Spo0A-activated transcription in vivo. To test the model in which the K356E and
      H359R substitutions in sigmaA interfere with the interaction of Spo0A and sigmaA,
      we examined the effects of alanine substitutions at these positions in sigmaA on
      sigmaA's ability to direct transcription in vivo and in vitro. We found that
      alanine substitutions at these positions specifically reduced expression from the
      sigmaA-dependent, Spo0A-dependent promoters, spoIIG and spoIIE, in vivo.
      Furthermore, we found that stimulation of spoIIG promoter activity by Spo0A in
      vitro was reduced by the single substitutions H359A and H359R in sigmaA.

PMID- 9287023
TI  - Nitrogen GATA factors participate in transcriptional regulation of vacuolar
      protease genes in Saccharomyces cerevisiae.
AB  - The expression of most nitrogen catabolic genes in Saccharomyces cerevisiae is
      regulated at the level of transcription in response to the quality of nitrogen
      source available. This regulation is accomplished through four GATA-family
      transcription factors: two positively acting factors capable of transcriptional
      activation (Gln3p and Gat1p) and two negatively acting factors capable of down
      regulating Gln3p- and/or Gat1p-dependent transcription (Dal80p and Deh1p).
      Current understanding of nitrogen-responsive transcriptional regulation is the
      result of extensive analysis of genes required for the catabolism of small
      molecules, e.g., amino acids, allantoin, or ammonia. However, cells contain
      another, equally important source of nitrogen, intracellular protein, which
      undergoes rapid turnover during special circumstances such as entry into
      stationary phase, and during sporulation. Here we show that the expression of
      some (CPS1, PEP4, PRB1, and LAP4) but not all (PRC1) vacuolar protease genes is
      nitrogen catabolite repression sensitive and is regulated by the GATA-family
      proteins Gln3p, Gat1p, and Dal80p. These observations extend the global
      participation of GATA-family transcription factors to include not only well
      studied genes associated with the catabolism of small nitrogenous compounds but
      also genes whose products are responsible for the turnover of intracellular
      macromolecules. They also point to the usefulness of considering control of the
      nitrogen-responsive GATA factors when studying the regulation of the protein
      turnover machinery.

PMID- 9287024
TI  - The transmission disadvantage of yeast mitochondrial intergenic mutants is
      eliminated in the mgt1 (cce1) background.
AB  - A trans-acting element, MGT1 (also called CCE1), has previously been shown to be
      required in Saccharomyces cerevisiae for the preferential transmission of petite
      mitochondrial DNA (mtDNA) molecules over wild-type mtDNA molecules. In the
      present study a possible role of this nuclear gene in the transmission of mtDNA
      from various respiration-competent mutants was studied. Several of these mutants,
      lacking one or the other of two biologically active mitochondrial intergenic
      sequences, were employed in genetic crosses. When these deletion mutants were
      crossed to the parental wild-type strain in the MGT1/CCE1 background, the progeny
      contained predominantly wild-type mtDNA molecules. When crosses were performed in
      the mgt1/cce1 background, the parental molecules interacted in zygotes and
      underwent homologous recombination but wild-type and intergenic-deletion alleles
      were transmitted with equal frequencies.

PMID- 9287025
TI  - Analysis of the role of the nnrR gene product in the response of Rhodobacter
      sphaeroides 2.4.1 to exogenous nitric oxide.
AB  - Rhodobacter sphaeroides 2.4.1, which is incapable of denitrification, has been
      found to carry nnrR, the nor operon, and nnrS, which are utilized for
      denitrification in R. sphaeroides 2.4.3. The gene encoding nitrite reductase was
      not found in 2.4.1. Expression of beta-galactosidase activity from a norB-lacZ
      fusion was activated when cells of 2.4.1 were incubated with NO-producing
      bacteria. This result indicates that the products of nnrR and the genes flanking
      it are utilized when 2.4.1 is growing in an environment where denitrification
      occurs.

PMID- 9287028
TI  - Properties of the phosphorylation reaction catalyzed by SpoIIAB that help to
      regulate sporulation of Bacillus subtilis.
AB  - Phosphorylation of SpoIIAA on Ser-58 catalyzed by SpoIIAB is important in the
      regulation of sporulation of Bacillus subtilis. Nucleotide binding experiments
      showed that the affinity of SpoIIAB for ATP was greatly increased in the presence
      of SpoIIAA or a mutant SpoIIAA in which Ser-58 had been changed to alanine. Study
      of the phosphorylation reaction showed that the Km for ATP and the Ki for ADP
      were both about 1 microM. The kinetics of phosphorylation of SpoIIAA by SpoIIAB
      were biphasic, comprising a rapid phase (leading to phosphorylation of 1 mol of
      SpoIIAA/mol of SpoIIAB) followed by a slower, steady-state phase. In the steady
      state, the rate-determining step proved to be the dissociation of a SpoIIAB-ADP
      complex. The rate of this dissociation was not affected significantly by changes
      in the concentration of ATP.

PMID- 9287026
TI  - BglG, the response regulator of the Escherichia coli bgl operon, is
      phosphorylated on a histidine residue.
AB  - We have shown previously that the activity of BglG, the response regulator of the
      bgl system, as a transcriptional antiterminator is modulated by the sensor BglF,
      which reversibly phosphorylates BglG. We show here that the phosphoryl group on
      BglG is present as a phosphoramidate, based on the sensitivity of phosphorylated
      BglG to heat, hydroxylamine, and acidic but not basic conditions. By analyzing
      the products of base-hydrolyzed phosphorylated BglG by thin-layer chromatography,
      we show that the phosphorylation occurs on a histidine residue. This result
      supports the notion that the bgl system is a member of a new family of bacterial
      sensory systems.

PMID- 9287027
TI  - A nuclear genetic lesion affecting Saccharomyces cerevisiae mitochondrial
      translation is complemented by a homologous Bacillus gene.
AB  - A novel Bacillus gene was isolated and characterized. It encodes a homolog of
      Saccharomyces cerevisiae Pet112p, a protein that has no characterized relative
      and is dispensable for cell viability but required for mitochondrial translation.
      Expression of the Bacillus protein in yeast, modified to ensure mitochondrial
      targeting, partially complemented the phenotype of the pet112-1 mutation,
      demonstrating a high degree of evolutionary conservation for this as yet
      unidentified component of translation.

PMID- 9287029
TI  - Identification and characterization of cell wall-cell division gene clusters in
      pathogenic gram-positive cocci.
AB  - Clusters of peptidoglycan biosynthesis and cell division genes (DCW genes) were
      identified and sequenced in two gram-positive cocci, Staphylococcus aureus and
      Enterococcus faecalis. The results indicated some similarities in organization
      compared with previously reported bacterial DCW gene clusters, including the
      presence of penicillin-binding proteins at the left ends and ftsA and ftsZ cell
      division genes at the right ends of the clusters. However, there were also some
      important differences, including the absence of several genes, the comparative
      sizes of the div1B and ftsQ genes, and a wide range of amino acid sequence
      similarities when the genes of the gram-positive cocci were translated and
      compared to bacterial homologs.

PMID- 9287031
TI  - High-frequency transposition of IS1373, the insertion sequence delimiting the
      amplifiable element AUD2 of Streptomyces lividans.
AB  - IS1373 is the putative insertion sequence delimiting the amplifiable unit AUD2 of
      Streptomyces lividans. Two IS1373-derived thiostrepton-resistant transposons,
      Tn5492 and Tn5494, transposed into multiple sites of the S. lividans chromosome
      at frequencies as high as 0.4 and 1%, respectively. Hence, IS1373 is a functional
      insertion sequence and its unique open reading frame, insA, encodes the
      transposase.

PMID- 9287033
TI  - Protein expression in response to folate stress in Escherichia coli.
AB  - Interruption of folate metabolism by trimethoprim results in the elevated
      expression of folate stress proteins in Escherichia coli. E. coli grown in
      culture medium supplemented with the folate-dependent metabolites glycine,
      methionine, and the purine nucleoside inosine shows reduced expression of folate
      stress proteins. The folate stress proteins include the universal stress protein,
      the ferric uptake regulatory repressor, and possibly, lipoamide dehydrogenase,
      the L protein component of the glycine cleavage enzyme complex.

PMID- 9287034
TI  - Are metabolic oscillations responsible for normal oscillatory insulin secretion?
AB  - Normal insulin secretion is oscillatory in vivo and in vitro, with a period of
      approximately 5-10 min. The mechanism of generating these oscillations is not yet
      established, but a metabolic basis seems most likely for glucose-stimulated
      secretion. The rationale is that 1) spontaneous oscillatory operation of
      glycolysis is a well-established phenomenon; 2) oscillatory behavior of
      glycolysis involves oscillations in the ATP/ADP ratio, which can cause
      alternating opening and closing of ATP-sensitive K+ channels, leading to the
      observed oscillations in membrane potential and Ca2+ influx in pancreatic beta
      cells, and may also have downstream effects on exocytosis; 3) spontaneous Ca2+
      oscillations are an unlikely basis in this case, since intracellular stores are
      not of primary importance in the stimulus-secretion coupling, and furthermore,
      insulin oscillations occur under conditions when intracellular Ca2+ levels are
      not changing; 4) a neural basis cannot account for insulin oscillations from
      perifused islets and clonal beta-cells or from transplanted islets or pancreas in
      vivo; 5) observed oscillations in metabolite levels and fluxes further support a
      metabolic basis, as does the presence in beta-cells of the oscillatory isoform of
      phosphofructokinase (PFK-M). The fact that normal oscillatory secretion is
      impaired in patients with NIDDM and in their near relatives suggests that such
      derangement may be involved in the development of the disease; furthermore, this
      probably reflects an early defect in the regulation and operation of the fuel
      metabolizing/sensing pathways of the pancreatic beta-cell.

PMID- 9287032
TI  - A flagellar sheath protein of Helicobacter pylori is identical to HpaA, a
      putative N-acetylneuraminyllactose-binding hemagglutinin, but is not an adhesin
      for AGS cells.
AB  - The gene encoding a 29-kDa flagellar sheath protein was cloned and found to be
      similar to hpaA, reported to encode an N-acetylneuraminyllactose-binding
      fibrillar hemagglutinin (D. G. Evans, T. K. Karjalainen, D. J. Evans, Jr., D. Y.
      Graham, and C. H. Lee, J. Bacteriol. 175:674-683, 1993). The transcriptional
      start was mapped by primer extension from Helicobacter pylori mRNA, indicating an
      active consensus promoter at a location different from that suggested by Evans et
      al. Immunogold labelling of the flagellar sheath with a monoclonal antibody to
      HpaA was demonstrated in four strains, contrary to previous reports of a surface
      (D. G. Evans, T. K. Karjalainen, D. J. Evans, Jr., D. Y. Graham, and C. H. Lee,
      J. Bacteriol. 175:674-683, 1993) or a cytoplasmic (P. W. O'Toole, L. Janzon, P.
      Doig, J. Huang, M. Kostrzynska, and T. J. Trust, J. Bacteriol. 177:6049-6057,
      1995) locale. Agglutination of erythrocytes and adherence to AGS cells by a delta
      hpaA mutant were no different from those of the parent strain, confirming a
      recent finding of O'Toole et al.

PMID- 9287036
TI  - Daily energy expenditure is related to plasma leptin concentrations in older
      African-American women but not men.
AB  - Recent research suggests that leptin may control body weight by regulating energy
      expenditure and energy intake in mice. To explore the possible role of leptin in
      the regulation of energy expenditure in humans, we used doubly-labeled water
      methodology to determine whether fasting plasma leptin concentrations were
      related to total daily energy expenditure (TEE) and its components, resting
      energy expenditure (REE) and physical activity energy expenditure (PAEE), in free
      living older African-American men (n = 21) and women (n = 25). Plasma leptin
      concentrations were higher in women than men, even after the adjustment for
      differences in fat mass (28 +/- 3 ng/ml for women vs. 17 +/- 3 ng/ml for men; P <
      0.01). The logarithm of plasma leptin concentrations correlated with fat mass in
      both women (r = 0.80) and men (r = 0.78) (P < 0.0001). After statistical
      adjustment for sex differences in fat-free mass and fat mass, women had lower TEE
      (22%) and REE (15%) (P < 0.01) and a trend (P = 0.08) toward lower PAEE, compared
      with men. After controlling for the effects of fat-free mass on energy
      expenditure, plasma leptin concentrations were related to REE (r = 0.68, P <
      0.001) and tended to be related to TEE (r = 0.37, P = 0.07) in African-American
      women but not men (r = 0.18 and -0.03, respectively). Plasma leptin
      concentrations were not related to PAEE in either men or women. These results
      suggest that leptin may contribute to the regulation of TEE in older African
      American women through its effects on resting energy metabolism, but the role of
      leptin in the regulation of energy expenditure is less apparent in older African
      American men.

PMID- 9287030
TI  - Isolation and characterization of the lacA gene encoding beta-galactosidase in
      Bacillus subtilis and a regulator gene, lacR.
AB  - We have isolated transposon insertions in the lacA gene encoding an endogenous
      beta-galactosidase of Bacillus subtilis. Upstream of the putative operon
      containing lacA is a negative regulator, lacR, which encodes a product related to
      a family of regulators that includes the lactose repressor, lacI, of Escherichia
      coli. New strains with insertions in the lacA gene should be of use in studies
      using lacZ fusions in B. subtilis.

PMID- 9287035
TI  - Hemodynamic actions of insulin in rat skeletal muscle: evidence for capillary
      recruitment.
AB  - Insulin-induced increases in blood flow are hypothesized to enhance overall
      glucose uptake by skeletal muscle. Whether the insulin-mediated changes in blood
      flow are associated with altered blood flow distribution and increased capillary
      recruitment in skeletal muscle is not known. In the present study, the effects of
      insulin on hemodynamic parameters in rat skeletal muscle in vivo were
      investigated. Mean arterial blood pressure, heart rate, femoral blood flow, hind
      leg vascular resistance, and glucose uptake were measured in control and
      euglycemic insulin-clamped (10 mU x min(-1) x kg[-1]) anesthetized rats. Blood
      flow distribution within the hind leg muscles was assessed by measuring the
      metabolism of 1-methylxanthine (1-MX), an exogenously added substrate for
      capillary xanthine oxidase. Insulin treatment had no effect on heart rate but
      significantly increased arterial blood pressure (12 mmHg) and femoral blood flow
      (80%) and decreased hind leg vascular resistance (31%). Changes were similar in
      magnitude and in time of onset to those reported in humans. Insulin treatment
      increased hind leg glucose uptake approximately fourfold and also increased hind
      leg 1-MX metabolism by 50%, suggesting increased exposure to endothelial xanthine
      oxidase. To ascertain whether the increased 1-MX metabolism was simply due to
      increased bulk femoral blood flow, epinephrine was infused at a dose (0.125
      microg x min(-) x kg[-1]) chosen to match the insulin-induced increase in femoral
      blood flow. This dose of epinephrine had no significant effects on arterial blood
      pressure or heart rate but increased femoral blood flow and lowered hind leg
      vascular resistance to a similar extent as insulin. Epinephrine did not
      significantly alter 1-MX metabolism as compared with control animals. These
      results demonstrate that insulin increases total hind leg blood flow and
      metabolism of 1-MX, suggesting a recruitment of capillary blood flow in rat hind
      leg not mimicked by epinephrine.

PMID- 9287037
TI  - Pioglitazone induces in vivo adipocyte differentiation in the obese Zucker fa/fa
      rat.
AB  - Thiazolidinediones are potent antidiabetic compounds, in both animal and human
      models, which act by enhancing peripheral sensitivity to insulin.
      Thiazolidinediones are high-affinity ligands for peroxisome proliferator
      activated receptor-gamma, a key factor for adipocyte differentiation, and they
      are efficient promoters of adipocyte differentiation in vitro. Thus, it could be
      questioned whether a thiazolidinedione therapy aimed at improving insulin
      sensitivity would promote the recruitment of new adipocytes in vivo. To address
      this problem, we have studied the in vivo effect of pioglitazone on glucose
      metabolism and gene expression in the adipose tissue of an animal model of
      obesity with insulin resistance, the obese Zucker (fa/fa) rat. Pioglitazone
      markedly improves insulin action in the obese Zucker (fa/fa) rat, but doubles its
      weight gain after 4 weeks of treatment. The drug induces a large increase of
      glucose utilization in adipose tissue, where it stimulates the expression of
      genes involved in lipid metabolism such as the insulin-responsive GLUT, fatty
      acid synthase, and phosphoenolpyruvate carboxykinase genes, but decreases the
      expression of the ob gene. These changes are related to both an enhanced
      adipocyte differentiation, as shown by the large increase in the number of small
      adipocytes in the retroperitoneal fat pad, and a direct effect of pioglitazone on
      specific gene expression (phosphoenolpyruvate carboxykinase and ob genes) in
      mature adipocytes.

PMID- 9287038
TI  - Role of the glucagon receptor COOH-terminal domain in glucagon-mediated signaling
      and receptor internalization.
AB  - The binding of glucagon to its hepatic receptor is known to result in a number of
      effects, including the intracellular accumulation of cAMP, the mobilization of
      intracellular Ca2+, and the endocytosis of glucagon and its receptor into
      intracellular vesicles. In this study, we begin to define the functional role of
      the COOH-terminal tail of the human glucagon receptor in glucagon-stimulated
      signal transduction and receptor internalization. We have created and expressed
      in Chinese hamster ovary (CHO) cells five truncation mutants in which the COOH
      terminal 24, 56, 62, 67, and 73 amino acids have been removed. Cells expressing
      relevant truncated receptors were assayed for cell surface expression by
      immunofluorescence, for ligand-binding properties, for cAMP and Ca2+-mediated
      signal transduction properties, and for receptor endocytosis. In addition, a
      mutant receptor containing seven serine-to-alanine mutations in the COOH-terminal
      tail was studied. Our results reveal the following: 1) a region of the COOH
      terminal tail that is required for proper cell surface expression, 2) the COOH
      terminal 62 amino acids, which comprise the majority of the tail, are not
      required for ligand binding, cAMP accumulation, or Ca2+ mobilization, and 3)
      phosphorylation of the COOH-terminal tail is crucial for glucagon-stimulated
      receptor endocytosis.

PMID- 9287039
TI  - Effects of metformin on lactate uptake and gluconeogenesis in the perfused rat
      liver.
AB  - To directly assess the effects of the biguanide, metformin, on hepatic
      gluconeogenesis, it was added at high therapeutic levels (90 microg/ml) to the
      medium perfusing an isolated rat liver. Lactate (1 mg/min) was infused
      simultaneously along with [14C]lactate with or without [3H]lactate. [6
      (3)H]glucose was added at the beginning of the perfusion in studies where
      [3H]lactate was not infused. Glucose levels decreased relative to control studies
      (metformin dose = 0) and lactate concentrations increased in this closed system.
      Quantitative analysis of the relationship between labeled glucose and lactate
      indicated that the flux of carbon from lactate to glucose and CO2 was halved,
      whereas reflux from glucose to lactate increased by approximately 80%. This was
      corroborated by measurement of labeled lactate extraction as well as glucose,
      CO2, and lactate production across the liver. Glycogen content of the liver fell
      by 60% relative to control and was greater for the gluconeogenic pathway. These
      data are consistent with an inhibitory action of metformin on gluconeogenesis,
      which is due to a primary inhibition of hepatic lactate uptake.

PMID- 9287040
TI  - Impaired glucose-induced insulin response in transgenic mice overexpressing the L
      phosphofructokinase gene.
AB  - The selective impairment of glucose-induced insulin secretion in NIDDM can be
      attributed to defects in the glucose-signaling system. An alteration in the
      activity of phosphofructokinase (PFK), a key enzyme in the glycolytic pathway,
      may play a role in the abnormal glucose-induced insulin secretion. In this study,
      we evaluated insulin secretion in transgenic (Tg) mice overexpressing the liver
      type subunit of phosphofructokinase (PFKL). Three independently derived Tg-PFKL
      lines showed random and postprandial hyperglycemia with diminished acute insulin
      response following intravenous glucose tolerance load. Isolated islets of Tg-PFKL
      mice exhibited a shift to the right of the glucose insulin dose curve. However,
      the maximal insulin secretory capacity, as well as the potentiation effect by
      arginine, were retained. PFK activity in Tg-PFKL islets was increased by 30-70%,
      because of the overexpression of PFKL. Conceivably, a selective overexpression of
      the PFKL isoform in Tg-PFKL mice altered the enzymatic properties of the
      tetrameric PFK and thereby affected glucose metabolism. A similar phenomenon was
      previously observed in transfected PC12-PFKL cells. The data show that
      overexpression of PFKL in transgenic mice was associated with diminished glucose
      induced insulin response and suggest a mechanism to explain the role of beta-cell
      PFK activity in glucose-induced insulin secretion.

PMID- 9287041
TI  - Identification of muscarinic receptor subtypes in RINm5F cells by means of
      polymerase chain reaction, subcloning, and DNA sequencing.
AB  - Carbachol can stimulate insulin release in RINm5F cells by a mechanism that does
      not involve the elevation of cytosolic free Ca2+ concentrations or the activation
      of conventional protein kinase Cs (Mol Pharmacol 47:863-870, 1995). Thus, a novel
      signal transduction pathway links the muscarinic activation of the cells to
      increased insulin secretion. The question arises as to whether the pathway
      results from a novel receptor, different from the five established muscarinic
      receptors, or whether a "normal" receptor in the RINm5F cell activates a novel
      pathway. To distinguish between these two possibilities, the muscarinic receptors
      in the RINm5F cell were identified. Using polymerase chain reaction, combined
      with subcloning and DNA sequencing techniques, the cDNAs that encode the
      established M3 and M4 receptors were identified. The cDNAs for the Ml, M2, and M5
      receptors were not found. Pharmacological studies showed a rank order of potency
      for muscarinic receptor subtype antagonists to inhibit carbachol-induced insulin
      release (half-maximal inhibitory concentration [pIC50] values given in
      parentheses): atropine (nonselective, 9.0) > 4-diphenyl-acetoxy-N-methyl
      piperidine methiodide (M3/M1, 8.6) > para-fluoro-hexahydrosiladiphenidol (M3,
      8.1) > hexahydrosiladiphenidol (M3, 8.0) > tropicamide (M4, 6.4) > pirenzepine
      (M1, 6.1) > methoctramine (M2, 5.9). This antagonist profile suggests that it is
      the M3 receptor that mediates carbachol-induced insulin release. In this case,
      the novel signaling involved in the unusual carbachol response would not be due
      to a novel receptor but to the well-characterized M3 receptor. It appears,
      therefore, that the novel portion of the signaling pathway lies downstream of the
      M3 receptor and may consist of products of phosphatidylinositol hydrolysis, other
      than inositol triphosphate and diacylglycerol, resulting from the activation of
      phospholipase C. While a contributory role of the M4 receptor cannot be ruled
      out, there is no evidence in its favor other than its presence in the cell.

PMID- 9287042
TI  - Glucose-induced insulin secretion in INS-1 cells depends on factors present in
      fetal calf serum and rat islet-conditioned medium.
AB  - To study the regulation of growth and differentiated function of insulin
      secreting cells, the rat insulinoma cell line INS-1 was cultured in a defined
      serum-free medium containing prolactin, IGF-I, and triiodothyronine, which was
      originally reported to maintain insulin secretion of islet cells. Growth and
      viability, as well as cellular insulin content of INS-1 cells in the defined
      medium, were comparable to the control cells cultured in the complete medium
      containing 10% fetal calf serum. However, after a 3-day culture in this medium,
      insulin secretion in response to glucose, pyruvate, and leucine was markedly
      blunted compared with the control cells (-78, -68, and -56%, respectively),
      whereas the response to 30 mmol/l K+ was only slightly decreased. In these cells:
      1) nutrient metabolism assessed by tetrazolium salt reduction was reduced in
      response to pyruvate and leucine, which are mainly metabolized in the
      mitochondria; 2) oxidation of both [3,4-(14)C]glucose and [1-(14)C]pyruvate was
      decreased (-22 and -32%, respectively); 3) glucose failed to depolarize the
      membrane potential, whereas tolbutamide was fully active; 4) video imaging
      analysis of cytosolic Ca2+ showed a decrease in the population of glucose
      responsive cells, while the response to 30 mmol/l K+ was preserved; 5) serum
      replenishment for 3 days restored glucose-induced insulin secretion.
      Interestingly, conditioned serum-free medium from rat islets maintained the
      insulin secretory function of INS-1 cells, although glucagon, somatostatin, and
      some other factors failed to restore the function. In contrast, conditioned media
      from HepG2, PC12, and human umbilical vein endothelial cells did not substitute
      for serum. Thus, the impaired insulin secretion of the cells cultured in the
      defined medium is best explained by defective mitochondrial metabolism. Islet
      cells, but not INS-1 cells, produce factors required for normal signal generation
      by nutrient secretagogues.

PMID- 9287043
TI  - Changes in pancreatic islet glucokinase and hexokinase activities with increasing
      age, obesity, and the onset of diabetes.
AB  - We examined changes in high- and low-Km glucose phosphorylating activity in
      pancreatic islet extracts from the prediabetic Zucker diabetic fatty (ZDF) rat
      between 5-6 weeks and 12 weeks of age (after the onset of diabetes). Comparisons
      were made between the activity observed in the ZDF rat and that seen in the ZDF
      lean control (ZLC) rat and the obese nondiabetic Zucker fatty (ZF) rat. At 5-6
      weeks of age, insulin resistant ZDF and ZF rats were hyperinsulinemic, compared
      with the ZLC rat, but had normal plasma glucose levels. Kinetic parameters (Vmax
      and Km for glucose) of hexokinase (HK) and Km of glucokinase (GCK) did not differ
      between groups. Islet GCK activity for ZDF and ZF rats was 1.7-fold greater than
      in ZLC rats (P < 0.02 and P < 0.001, respectively). By 12 weeks of age,
      hypersecretion of insulin at 5.0 mmol/l glucose was observed in perifused islets
      from both obese groups relative to the ZLC rat. Islets from ZDF rats failed to
      increase insulin secretion in response to increased glucose concentration. Group
      differences in the kinetic parameters for GCK or in the Km values for HK were not
      significant. Islet HK activity for ZDF and ZF rats was 1.9-fold (P < 0.05) and
      1.7-fold (P < 0.05) greater, respectively, than for ZLC rats. Compared with the 5
      to 6-week-old animals, HK activity increased 3.1-fold (P < 0.001), 2.5-fold (P <
      0.002), and 2.0-fold (P < 0.05) for ZDF, ZF, and ZLC rats, respectively.
      Differences in GCK activity between 5- to 6- and 12-week-old rats were not
      significant for any of the groups. We conclude: 1) increased islet glucose
      phosphorylating activity is present in insulin resistant and hyperinsulinemic ZF
      and ZDF rats, relative to the ZLC rat; 2) at 12 weeks of age, hyperinsulinemic
      ZDF and ZF rats demonstrated significant increases in HK activity, compared with
      lean controls; and 3) deficiency in GCK activity does not explain failure of
      diabetic ZDF islets to respond to glucose, since differences between diabetic ZDF
      and nondiabetic ZF rats were not statistically significant. Increases in
      pancreatic islet phosphorylating activity seem to be important in maintaining
      basal hyperinsulinemia in insulin-resistant animals, but do not appear to play a
      role in the progression to glucose intolerance and diabetes.

PMID- 9287045
TI  - Insulin administration enhances growth of the beta-cell mass in streptozotocin
      treated newborn rats.
AB  - We have previously reported that the damage caused by streptozotocin (STZ)
      administration to the beta-cells in newborn rats was followed by spontaneous
      recovery from neonatal diabetes. Our present data indicate that STZ
      administration on the day of birth (day 1) reduced the total beta-cell mass on
      day 4 to only 10% of the normal value and that after such damage, 27% of the
      corresponding normal beta-cell mass was spontaneously regained on day 7. During
      days 4-7, the contribution of the predicted beta-cell growth (due to the
      replication of preexisting differentiated beta-cells) to the total beta-cell
      growth represented only 56%. Therefore, recruitment of new beta-cells from a
      precursor pool indeed represents a significant mechanism for beta-cell
      regeneration after STZ during this period of life. Here, we report for the first
      time that 1) insulin therapy from days 2 to 4 did not significantly influence the
      occurrence of beta-cell damage after STZ administration (total beta-cell mass on
      day 4 was reduced to 12% of the normal value) and 2) insulin therapy from days 2
      to 6 did improve the otherwise spontaneous beta-cell regeneration, since on day 7
      total beta-cell mass was 44% of the corresponding normal beta-cell mass. During
      days 4-7, the contribution of the predicted beta-cell growth to the total beta
      cell growth represented only 32% in the insulin-treated STZ group. Finally the
      insulin-favored regeneration of the beta-cells reflects both an increased
      replication from differentiated beta-cells and an increased neogenesis from
      precursor/stem cells, with this last pathway being preferentially activated.

PMID- 9287044
TI  - Localization of the ATP-sensitive K+ channel subunit Kir6.2 in mouse pancreas.
AB  - Kir6.2, a member of the inward rectifier K+ channel family, is a component of the
      ATP-sensitive K+ (K[ATP]) channel considered to play a key role in glucose
      induced insulin secretion. We studied the distribution of Kir6.2 in mouse
      pancreas at the cellular level. The sites of Kir6.2 mRNA expression were
      determined by in situ hybridization histochemistry with a digoxigenin (DIG)
      labeled antisense cRNA probe. The hybridization signal was unevenly present
      throughout the islets of Langerhans, while no distinct signal was detected in
      exocrine acinar cells. This distribution was confirmed by another cRNA probe
      complementary to a different region of Kir6.2 mRNA. In situ hybridization and
      immunofluorescence staining of serial sections with the anti-insulin, the anti
      glucagon, and the anti-somatostatin antibodies showed Kir6.2 mRNA to be present
      in alpha-, beta-, and delta-cells. Furthermore, immunofluorescence staining with
      antibody raised against Kir6.2 revealed that Kir6.2 protein is localized within
      the pancreatic islets and is not found in exocrine pancreas. Kir6.2 was further
      shown to be located together with insulin, glucagon, or somatostatin. The
      positive staining of Kir6.2 appeared concentrated along the contour of each islet
      cell, suggesting that Kir6.2 is at the plasma membrane of islet cells. These
      results suggest that Kir6.2, as a component of K(ATP) channels, is an important
      molecule in the regulation of all the release of insulin, glucagon, and
      somatostatin.

PMID- 9287046
TI  - rhIGF-I administration reduces insulin requirements, decreases growth hormone
      secretion, and improves the lipid profile in adults with IDDM.
AB  - IDDM is associated with elevated circulating levels of growth hormone (GH) and
      reduced insulin-like growth factor I (IGF-I). GH antagonizes the action of
      insulin-increasing insulin requirements in IDDM. The effects of subcutaneously
      administered rhIGF-I on glycemic control, insulin requirements, and GH secretion
      were studied in eight adults with IDDM. Patients received either placebo or rhIGF
      I (50 microg/kg b.i.d.) for 19 days in a randomized, double-blind, parallel
      design, placebo-controlled trial. Overnight GH, plasma glucose, free insulin, IGF
      I, fructosamine, and lipid profiles were assessed during this period. rhIGF-I
      therapy increased IGF-I concentration from 117.1 +/- 14.2 (mean +/- SE) ng/ml
      (baseline) to 310.5 +/- 40.6 and 257.1 +/- 41.2 ng/ml on day 5 (P < 0.01 vs.
      baseline) and day 20 (P < 0.01 vs. baseline), respectively. After 19 days of
      rhIGF-I treatment, fructosamine concentrations were unchanged compared with
      baseline (439 +/- 32 vs. 429 +/- 35 micromol/l, day -1 vs. day 20, respectively),
      yet insulin requirements were decreased by approximately 45% (0.67 +/- 0.08 vs.
      0.36 +/- 0.07 U x kg(-1) x day(-1), day -1 vs. day 19, respectively, P < 0.005).
      After 4 days of rhIGF-I therapy, there was a decrease in free insulin levels
      (8.38 +/- 1.47 vs. 4.98 +/- 0.84 mU/l, P < 0.05), mean overnight GH concentration
      (12.6 +/- 3.3 vs. 3.8 +/- 2.1 mU/l, P = 0.05), and total cholesterol and
      triglycerides (4.68 +/- 0.31 vs. 4.25 +/- 0.35 mmol/l, P < 0.05, 1.27 +/- 0.19
      vs. 0.95 +/- 0.21 mmol/l, P < 0.001, respectively). There was no change in any
      variable in the placebo-treated patients. This study demonstrates that
      subcutaneous administration of rhIGF-I decreases insulin requirements and
      improves the plasma lipid profile while maintaining glycemic control in adults
      with IDDM. The excess nocturnal release of GH, characteristic of IDDM, is also
      decreased by rhIGF-I therapy.

PMID- 9287047
TI  - Prediction of type 1 diabetes postpartum in patients with gestational diabetes
      mellitus by combined islet cell autoantibody screening: a prospective multicenter
      study.
AB  - Women with gestational diabetes mellitus (GDM) have a considerable risk of
      developing diabetes later in life. To determine the predictive value of
      autoantibody markers in gestational diabetic pregnancy for the development of
      type 1 diabetes postpartum, we tested 437 patients with GDM (289 women treated
      with diet only [GDM-A] and 148 requiring insulin treatment during pregnancy [GDM
      B]) for antibodies to islet cells (ICAs), GAD (GADAs), and tyrosine phosphatase
      ICA512/IA-2 (IA2As). We prospectively followed them with repeated oral glucose
      tolerance tests and antibody determinations for up to 7 years postpartum (mean,
      1.6 years; range, 0-7.2 years). The cumulative risk of diabetes up to 5 years
      postpartum was 17% (95% CI 12-22%). The risk of type 1 diabetes was 3% (2-5%) by
      9 months and 7% (4-9%) 2 years after delivery. At delivery, 8.5% of all patients
      were ICA+, 9.5% were GADA+, 6.2% were IA2A+, and 18.1% were positive for at least
      one antibody (12.6% for GDM-A vs. 30.4% for GDM-B, P < 0.0001). During follow-up,
      GADAs persisted in 75%, ICAs in 35%, and IA2As in 30% of the subjects positive
      for the respective marker at delivery. By 2 years postpartum, 29% (19-39%) of
      patients positive for at least one antibody developed type 1 diabetes, compared
      with 2% (1-4%) of antibody-negative patients (P < 0.0001). Thereby, the risk for
      type 1 diabetes 2 years postpartum increased with the number of antibodies
      present at delivery from 17% (6-28%) for one antibody, to 61% (30-91%) for two
      antibodies, and to 84% (55-100%) for 3 antibodies. Risk of progression to type 1
      diabetes postpartum was also associated with the status of parity. Women with one
      or more pregnancies before the index pregnancy had a higher risk for type 1
      diabetes 2 years after delivery (14.7% [4.9.-24.5%]) than women having their
      first (i.e., index) pregnancy (5% [2.9-7.1%]) (P < 0.006). A comparison of
      different prediction strategies showed that single antibody screening with GADA
      yielded the highest sensitivity of 63% (45-75%), compared with ICA (48% [31-65%])
      and IA2A (34% [13-47%]). Combined screening with two autoantibodies increased
      sensitivity to 74% (58-90%) and 75% (60-92%) when using GADA plus ICA or GADA
      plus IA2A, respectively. Screening with all three markers improved sensitivity
      further to 82% (67-100%). Beta-cell autoantibodies determined at delivery in
      women with GDM are highly predictive for the development of type 1 diabetes
      postpartum. Autoantibody screening in pregnant women with GDM from populations at
      high risk for type 1 diabetes should therefore be considered to allow early
      diagnosis and appropriate therapy.

PMID- 9287048
TI  - The TNF-alpha gene Nco I polymorphism influences the relationship among insulin
      resistance, percent body fat, and increased serum leptin levels.
AB  - Tumor necrosis factor-alpha (TNF-alpha), acting as a modulator of gene expression
      in adipocytes, is implicated in the development of insulin resistance and
      obesity. The aim of this study was to investigate whether the Nco I polymorphism
      of the TNF-alpha gene influences the relationship among insulin resistance,
      percent body fat, and serum leptin levels. A sample of 38 subjects (19 men, mean
      age 36.2 +/- 1.9 years, BMI 28.8 +/- 1.2 kg/m2, range 22.2-35.7; and 19 women,
      age 34.9 +/- 1.4 years, BMI 28.1 +/- 0.8 kg/m2, range 19-37.9) was divided into
      two groups on the basis of the Nco I genotype. Twenty-three subjects were (+/+)
      homozygotes for the presence of the Nco I restriction site that is associated
      with a guanine at position -308 of the TNF-alpha promoter. Of the other subjects,
      12 were (+/-) heterozygotes and 3 (-/-) homozygotes for the absence of the
      restriction site, resulting from a guanine-to-adenine substitution at position 
      308 of the TNF-alpha promoter. This substitution (termed TNF-2) leads to higher
      rate of transcription of TNF-alpha than the wild-type allele TNF-1 in vitro. TNF
      1 (+/+) and TNF-2 (+/- and -/-) groups of subjects were comparable in sex, age,
      BMI, waist-to-hip ratio, and several skinfold measurements. Basal serum insulin
      was greater (14.2 +/- 2 vs. 9.2 +/- 0.9 mU/l, P = 0.041) in the TNF-2 group in
      the presence of comparable serum glucose concentration. The integrated area under
      the curve of serum insulin concentrations, measured in response to a 75-g oral
      glucose challenge, and the percent body fat, measured by bioelectric impedance,
      were significantly increased in TNF-2 subjects (226.8 +/- 33 vs. 139.4 +/- 17.8
      mU/l, P = 0.032; 33.6 +/- 2.8 vs. 24.9 +/- 2%, P = 0.01). TNF-2 subjects also
      showed a decreased insulin sensitivity index, as determined by the frequently
      sampled intravenous glucose tolerance test with minimal model analysis (1.9 +/-
      0.4 vs. 3.05 +/- 0.3 min(-1) x mU(-1) x l(-1), P = 0.03). These differences were
      more marked among women. Paralleling the known relationship between insulin and
      leptin levels, serum leptin concentration was clearly increased in the TNF-2
      group (19.6 +/- 3.4 vs. 11.1 +/- 1.5 ng/ml, P = 0.03). Therefore, (+/-)
      heterozygotes and (-/-) homozygotes may be more susceptible to developing insulin
      resistance and increased percent body fat. Results of the present study suggest
      that TNF-alphaNco I polymorphism may exacerbate the alterations in leptin levels
      normally found among insulin-resistant subjects.

PMID- 9287049
TI  - Vascular endothelial growth factor-induced retinal permeability is mediated by
      protein kinase C in vivo and suppressed by an orally effective beta-isoform
      selective inhibitor.
AB  - Increased vascular permeability and excessive neovascularization are the
      hallmarks of endothelial dysfunction, which can lead to diabetic macular edema
      and proliferative diabetic retinopathy in the eye. Vascular endothelial growth
      factor (VEGF) is an important mediator of ocular neovascularization and a known
      vasopermeability factor in nonocular tissues. In these studies, we demonstrate
      that intravitreal injection of VEGF rapidly activates protein kinase C (PKC) in
      the retina at concentrations observed clinically, inducing membrane translocation
      of PKC isoforms alpha, betaII, and delta and >threefold increases in retinal
      vasopermeability in vivo. The effect of VEGF on retinal vascular permeability
      appears to be mediated predominantly by the beta-isoform of PKC with >95%
      inhibition of VEGF-induced permeability by intravitreal or oral administration of
      a PKC beta-isoform-selective inhibitor that did not inhibit histamine-mediated
      effects. These studies represent the first direct demonstration that VEGF can
      increase intraocular vascular permeability through activation of PKC in vivo and
      suggest that oral pharmacological therapies involving PKC beta-isoform-selective
      inhibitors may prove efficacious for the treatment of VEGF-associated ocular
      disorders such as diabetic retinopathy.

PMID- 9287050
TI  - Advanced glycation end product-induced activation of NF-kappaB is suppressed by
      alpha-lipoic acid in cultured endothelial cells.
AB  - Depletion of cellular antioxidant defense mechanisms and the generation of oxygen
      free radicals by advanced glycation end products (AGEs) have been proposed to
      play a major role in the pathogenesis of diabetic vascular complications. Here we
      demonstrate that incubation of cultured bovine aortic endothelial cells (BAECs)
      with AGE albumin (500 nmol/l) resulted in the impairment of reduced glutathione
      (GSH) and ascorbic acid levels. As a consequence, increased cellular oxidative
      stress led to the activation of the transcription factor NF-kappaB and thus
      promoted the upregulation of various NF-kappaB-controlled genes, including
      endothelial tissue factor. Supplementation of the cellular antioxidative defense
      with the natural occurring antioxidant alpha-lipoic acid before AGE albumin
      induction completely prevented the AGE albumin-dependent depletion of reduced
      glutathione and ascorbic acid. Electrophoretic mobility shift assays (EMSAs)
      revealed that AGE albumin-mediated NF-kappaB activation was also reduced in a
      time- and dose-dependent manner as long as alpha-lipoic acid was added at least
      30 min before AGE albumin stimulation. Inhibition was not due to physical
      interactions with protein DNA binding, since alpha-lipoic acid, directly included
      into the binding reaction, did not prevent binding activity of recombinant NF
      kappaB. Western blots further demonstrated that alpha-lipoic acid inhibited the
      release and translocation of NF-kappaB from the cytoplasm into the nucleus. As a
      consequence, alpha-lipoic acid reduced AGE albumin-induced NF-kappaB mediated
      transcription and expression of endothelial genes relevant in diabetes, such as
      tissue factor and endothelin-1. Thus, supplementation of cellular antioxidative
      defense mechanisms by extracellularly administered alpha-lipoic acid reduces AGE
      albumin-induced endothelial dysfunction in vitro.

PMID- 9287051
TI  - Myocardial glucose uptake in patients with NIDDM and stable coronary artery
      disease.
AB  - Whole body insulin resistance characterizes patients with NIDDM, but it is not
      known whether insulin also has impaired ability to stimulate myocardial glucose
      uptake (MGU) in these patients. This study was designed to evaluate MGU as
      measured by 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) and positron emission
      tomography (PET) in patients with NIDDM and stable coronary artery disease (CAD)
      under standardized metabolic conditions. Eight patients with NIDDM, 11
      nondiabetic patients with CAD, and 9 healthy control subjects were enrolled in
      the study. MGU was quantitated in the normal myocardial regions with [18F]FDG and
      PET and the whole body glucose disposal by glucose-insulin clamp technique (serum
      insulin, -430 pmol/l). Plasma glucose and serum insulin concentrations were
      comparable in all groups during PET studies. The whole body glucose uptake was
      45% lower in NIDDM patients (22 +/- 9 micromol x min(-1) X kg(-1) body wt [mean
      +/- SD]), compared with healthy control subjects (40 +/- 17 micromol x min(-1) x
      kg(-1) body wt, P < 0.05). In CAD patients, whole body glucose uptake was 30 +/-
      9 micromol x min(-1) x kg(-1) body wt (NS between the other groups). MGU was
      similar in the normal segments in all three groups (69 +/- 28 micromol x min(-1)
      x 100 g(-1) in NIDDM patients, 72 +/- 17 micromol x min(-1) x 100 g(-1) in CAD
      patients, and 76 +/- 10 micromol x min(-1) x 100 g(-1) in healthy control
      subjects, NS). No correlation was found between whole body glucose uptake and
      MGU. As studied by [18F]FDG PET under stable normoglycemic hyperinsulinemic
      conditions, MGU is not reduced in patients with NIDDM and CAD in spite of
      peripheral insulin resistance. These findings suggest that there is no
      significant defect in MGU in patients with NIDDM.

PMID- 9287052
TI  - Glucose-induced protein kinase C activation regulates vascular permeability
      factor mRNA expression and peptide production by human vascular smooth muscle
      cells in vitro.
AB  - Hyperglycemia is an independent risk factor for the development of diabetic
      microvascular disease. Vascular permeability factor (VPF)/vascular endothelial
      growth factor (VEGF) is a potent cytokine family that induces angiogenesis and
      markedly increases endothelial permeability. VPF is produced by many cell types,
      including vascular smooth muscle (VSM) cells, and has been implicated in the
      pathogenesis of neovascularization and endothelial dysfunction in diabetes. This
      study used cultured human VSM cells to study the regulation of VPF production and
      determine whether elevated glucose concentrations, per se, are a sufficient
      stimulus for increased VPF production by human cells. In human VSM cells, high
      extracellular glucose concentrations (20 mmol/l) increased VPF mRNA expression
      within 3 h (3-fold vs. glucose 5 mmol/l) and significantly increased VPF peptide
      production within 24 h (1.5-fold) in a time- and glucose concentration-dependent
      manner. The high glucose-induced increase in VPF mRNA expression was rapidly
      reversed after normalizing the extracellular glucose concentration and was
      specific for a high D-glucose concentration, as these effects were not reproduced
      by osmotic control media containing elevated concentrations of mannitol or L
      glucose. High glucose concentrations activate protein kinase C (PKC) in human VSM
      cells, and PKC inhibitors (H-7 or chelerythrine chloride) or PKC downregulation
      each prevented the glucose-induced increases in VPF mRNA expression by human VSM
      cells. In conclusion, high glucose concentrations directly increase VPF mRNA
      expression and peptide production by human VSM cells via a PKC-dependent
      mechanism. These results demonstrate a cellular mechanism, whereby hyperglycemia
      could directly contribute to the development of endothelial dysfunction and
      neovascularization in diabetes.

PMID- 9287054
TI  - Exonic and intronic sequence variation in the human leptin receptor gene (LEPR).

PMID- 9287053
TI  - Mutations in the hepatocyte nuclear factor-1alpha/MODY3 gene in Japanese subjects
      with early- and late-onset NIDDM.
AB  - Recent studies have shown that mutations in the hepatocyte nuclear factor (HNF)
      1alpha gene are the cause of maturity-onset diabetes of the young type 3 (MODY3).
      We have screened 193 unrelated Japanese subjects with NIDDM for mutations in this
      gene: 83 with early-onset NIDDM (diagnosis at <30 years of age) and 110 with late
      onset NIDDM (diagnosis > or = 30 years of age). All of the members of the latter
      group also had at least one sibling with NIDDM. The 10 exons, flanking introns,
      and promoter region were amplified using polymerase chain reaction and were
      sequenced directly. Mutations were found in 7 of the 83 (8%) unrelated subjects
      with early-onset NIDDM. The mutations were each different and included four
      missense mutations (L12H, R131Q, K205Q, and R263C) and three frameshift mutations
      (P379fsdelCT, T392fsdelA, and L584S585fsinsTC). One of the 110 subjects with late
      onset NIDDM was heterozygous for the missense mutation G191D. This subject, who
      was diagnosed with NIDDM at 64 years of age, also had a brother with NIDDM (age
      at diagnosis, 54 years) who carried the same mutation, suggesting that this
      mutation contributed to the development of NIDDM in these two siblings. None of
      these mutations were present in 50 unrelated subjects with normal glucose
      tolerance (100 normal chromosomes). Mutations in the HNF-1alpha gene occur in
      Japanese subjects with NIDDM and appear to be an important cause of early-onset
      NIDDM in this population. In addition, they are present in about 1% of subjects
      with late-onset NIDDM.

PMID- 9287055
TI  - Mutations in the hepatocyte nuclear factor-1alpha gene (MODY3) are not a major
      cause of late-onset NIDDM in Japanese subjects.

PMID- 9287056
TI  - TNFa microsatellite polymorphism modulates the risk of IDDM in Caucasians with
      the high-risk genotype HLA DQA1*0501-DQB1*0201/DQA1*0301-DQB1*0302. Belgian
      Diabetes Registry.

PMID- 9287057
TI  - Low plasma leptin in response to dietary fat in diabetes- and obesity-prone mice.
AB  - Despite the fact that mutations resulting in the absence of leptin or its
      receptor have been associated with severe obesity and diabetes, such mutations do
      not appear to be responsible for most human obesity. Indeed, diet-induced obesity
      in animals and humans has been characterized by hyperleptinemia. This has been
      interpreted as evidence for leptin resistance. However, no careful longitudinal
      studies evaluating the role of leptin in the development of obesity exist. We
      report a series of studies in A/J and C57BL/6J (B/6) mice that demonstrate a
      direct relationship between the ability to increase plasma leptin levels in
      response to a high-fat diet and resistance to the subsequent development of
      obesity and diabetes. While leptin levels are similar in lean, low-fat-fed A/J
      and B/6 mice, the effects of a high-fat diet on plasma leptin differ dramatically
      between the two strains. After 4 weeks of high-fat feeding, leptin levels in A/J
      mice increased 10-fold, and this elevated level was maintained independent of
      weight gain throughout a 14-week feeding period. However, in B/6 mice, leptin
      levels remained at least twofold lower and only rose very gradually along with a
      significant increase in adiposity, hyperglycemia, and hyperinsulinemia. These
      differences in the response of leptin to diet are independent of food intake and
      plasma insulin levels during the 1st month of feeding. Further, we demonstrated
      that leptin administration did not influence the expression of the novel
      uncoupling protein UCP2, which also responds to dietary fat. From these results,
      we suggest that the response of leptin to fat feeding may be an important
      predictor of the development of subsequent obesity.

PMID- 9287058
TI  - Novel glucosensor for hypoglycemic detection localized to the portal vein.
AB  - In this investigation, we sought to constrain the locus of essential portohepatic
      glucosensors and test the hypothesis that they reside strictly in the portal vein
      and not the liver. Male Wistar rats were chronically cannulated in the carotid
      artery (sampling), jugular vein (infusion), and portal vein, either adjacent to
      (POR[ADJ], 0.6 +/- 0.1 cm, n = 6) or upstream from (POR[UPS], 2.7 +/- 0.1 cm, n =
      8) the liver. Animals were exposed to one of three protocols distinguished by the
      site of glucose infusion: POR(UPS), POR(ADJ), or peripheral (PER). Systemic
      hypoglycemia (2.4 +/- 0.1 mmol/l) was induced via jugular vein insulin infusion
      (50 mU x kg(-1) x min[-1]). Arterial plasma catecholamines were assessed at basal
      (-30 and 0 min) and during sustained hypoglycemia (60, 75, 90, 105 min). By
      design, hepatic glucose was significantly elevated during POR(UPS) and POR(ADJ)
      versus PER (4.3 +/- 0.1 vs. 2.4 +/- 0.1 mmol/l, respectively; P < 0.05). There
      were no significant differences between protocols in arterial glucose or insulin
      concentrations (9,372 +/- 1,798 pmol/l). When liver and systemic glucose
      concentrations were allowed to fall concomitantly (PER), epinephrine was elevated
      16-fold above basal levels (3.0 +/- 0.6 vs. 46.4 +/- 4.3 nmol/l, P < 0.001). When
      portohepatic normoglycemia was maintained during POR(UPS), a 67% suppression in
      the epinephrine response versus that during PER was observed (P < 0.001).
      However, when the cannula was advanced adjacent to the liver, by comparison with
      PER, there was no suppression in the sympathoadrenal response (P = 0.73). While
      both POR(UPS) and POR(ADJ) yielded elevated liver glycemia in the face of
      systemic hypoglycemia, only POR(UPS) yielded an elevated portal vein glucose
      concentration. That only POR(UPS) resulted in a significant suppression of the
      sympathoadrenal response is consistent with the localization of the glucosensors
      to the portal vein.

PMID- 9287059
TI  - Targeted disruption of the tumor necrosis factor-alpha gene: metabolic
      consequences in obese and nonobese mice.
AB  - To address the hypothesis that tumor necrosis factor (TNF)-alpha has a role in
      obesity-associated insulin resistance or the regulation of in vivo lipid
      metabolism, mice with targeted disruption of the TNF-alpha gene were generated
      and studied. The absence of TNF-alpha protein in TNF-null (-/-) mice was
      confirmed. Lean or obese (gold-thioglucose [GTG]-injected) homozygous (-/-) mice
      were compared with lean or obese age- and sex-matched wild-type (+/+) mice
      derived from the same line at 13, 19, and 28 weeks of age. The following
      parameters were significantly affected in lean -/- versus +/+ mice: Body weight
      was not affected until week 28 (decreased by 14%); epididymal fat pad weight also
      decreased (25%) at this time, as did percentage body fat (16%), while percentage
      body protein was increased 13%. Fed plasma insulin levels decreased 47% (28
      weeks), triglyceride levels decreased (all three ages; maximum 35% at 19 weeks),
      and fed plasma leptin decreased 33% (28 weeks). Fasting glucose was slightly
      (10%) reduced, but the glucose response to an oral glucose tolerance test (OGTT)
      was not affected. There was a trend (NS) toward increased total adipose tissue
      lipoprotein lipase in -/- versus +/+ mice. GTG-treatment resulted in obese -/-
      and +/+ mice with equal mean body weights (42 and 58% increased weight versus
      lean mice). The following parameters were significantly different in obese -/-
      mice: fasting plasma glucose decreased 13% (28 weeks), fed plasma insulin
      decreased 67% (28 weeks), and insulin response to OGTT was decreased by 50%. For
      both groups of obese mice, glucose levels during the OGTT were substantially
      increased compared with those in lean mice; however, mean stimulated glucose
      levels were 20% lower in obese -/- versus +/+ mice. We conclude 1) that TNF-alpha
      functions to regulate plasma triglycerides and body adiposity and 2) that
      although TNF-alpha contributes to reduced insulin sensitivity in older or obese
      mice, the absence of TNF-alpha is not sufficient to substantially protect against
      insulin resistance in the GTG hyperphagic model of rodent obesity.

PMID- 9287061
TI  - The survival rate of Actinobacillus actinomycetemcomitans, Porphyromonas
      gingivalis, and Bacteroides forsythus following 4 randomized treatment
      modalities.
AB  - The overall goal of this clinical study was to determine the short-term anti
      infective effects of four randomized treatment modalities on Actinobacillus
      actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), and Bacteroides
      forsythus (Bf) and determine the effects of bacterial survival on treatment
      outcomes in patients with adult periodontitis. Twelve adult patients requiring
      therapy for moderate periodontitis were selected for this study. All patients had
      at least one tooth in each quadrant that had an inflamed pocket of probing depth
      > or =5 mm with probing attachment loss that harbored at least one of the
      following three periodontal pathogens: Aa, Pg, or Bf. The number of target
      organisms per site was determined pre-operatively, at 1 week, and 1 month and 3
      months postoperatively utilizing DNA probes. One quadrant in each patient was
      randomly assigned to each one of the following four treatment groups: 1) scaling
      and root planing (SRP group); 2) pocket reduction through osseous surgery and
      apically-positioned flap (OS group); 3) modified Widman flap (MWF group); and 4)
      modified Widman flap and topical application of saturated citric acid at pH 1 for
      3 minutes (CA group). The 4 treatment modalities were performed in one
      appointment. No postoperative antibiotics were used. Patients were instructed to
      supplement their daily oral hygiene with chlorohexidine oral rinse during the
      study. The results of this investigation indicated that: 1) none of the treatment
      modalities was effective in eliminating the target species; 2) the incidence of
      infected sites for all groups was 100% preoperatively; 62.5%, 33.3%, and 31.3% at
      1 week, and 1 and 3 months postoperatively, respectively; 3) these infected sites
      lost 1.1 +/- 0.4 mm of probing attachment compared to gain of 0.0 +/- 0.3 mm for
      uninfected sites; 4) the infected sites had higher plaque and bleeding on probing
      0.9 +/- 0.3, 73 +/- 12%, respectively, compared to 0.3 +/- 0.1 and 30 +/- 8% for
      the uninfected sites; and 5) no statistically significant differences were
      detected among the infected sites in regard to gingival index (1.0 +/- 0.2 vs.
      0.8 +/- 0.1) or probing depth (3.5 +/- 0.4 vs. 3.0 +/- 0.1 mm). These results
      indicate that bacterial survival negatively affects the short-term clinical
      outcomes of non-surgical and surgical periodontal therapy.

PMID- 9287060
TI  - Treatment of periodontal disease in diabetics reduces glycated hemoglobin.
AB  - Periodontal disease is a common infection-induced inflammatory disease among
      individuals suffering from diabetes mellitus. The purpose of this study was to
      assess the effects of treatment of periodontal disease on the level of metabolic
      control of diabetes. A total of 113 Native Americans (81 females and 32 males)
      suffering from periodontal disease and non-insulin dependent diabetes mellitus
      (NIDDM) were randomized into 5 treatment groups. Periodontal treatment included
      ultrasonic scaling and curettage combined with one of the following antimicrobial
      regimens: 1) topical water and systemic doxycycline, 100 mg for 2 weeks; 2)
      topical 0.12% chlorhexidine (CHX) and systemic doxycycline, 100 mg for 2 weeks;
      3) topical povidone-iodine and systemic doxycycline, 100 mg for 2 weeks; 4)
      topical 0.12% CHX and placebo; and 5) topical water and placebo (control group).
      Assessments were performed prior to and at 3 and 6 months after treatment and
      included probing depth (PD), clinical attachment level (CAL), detection of
      Porphyromonas gingivalis in subgingival plaque and determination of serum glucose
      and glycated hemoglobin (HbA1c). After treatment all study groups showed clinical
      and microbial improvement. The doxycycline-treated groups showed the greatest
      reduction in probing depth and subgingival Porphyromonas gingivalis compared to
      the control group. In addition, all 3 groups receiving systemic doxycycline
      showed, at 3 months, significant reductions (P < or = 0.04) in mean HbA1c
      reaching nearly 10% from the pretreatment value. Effective treatment of
      periodontal infection and reduction of periodontal inflammation is associated
      with a reduction in level of glycated hemoglobin. Control of periodontal
      infections should thus be an important part of the overall management of diabetes
      mellitus patients.

PMID- 9287062
TI  - In vitro antifungal properties of mouthrinses containing antimicrobial agents.
AB  - The purpose of this study was to investigate the in vitro antifungal properties
      of seven commercial mouthrinses containing antimicrobial agents. These included
      cetylpyridinium chloride (CPC), chlorhexidine digluconate (CHX), hexetidine
      (HEX), sanguinarine (SNG), and triclosan (TRN). The minimum fungicidal
      concentration (MFC) against six species of yeasts was determined by a broth
      macrodilution method. The kill-time of mouthrinses at half the concentration of
      the commercial formulations was also determined. MFCs were achieved with each
      mouthrinse, except the SNG-containing mouthrinse, against all the organisms being
      tested. However, the CPC-containing mouthrinse appeared more active than the
      other products (P < 0.001). There were no significant differences in MFC values
      among CHX mouthrinse products, once adjusted for initial concentration
      differences (P = 0.1). Kill-times of mouthrinses containing either CHX or CPC
      were less than or equal to 180 seconds with all the species of yeasts, and no
      significant differences were found among these products (P = 0.18). On the other
      hand, mouthrinses containing either TRN or HEX did not show a lethal effect on
      Candida albicans, Candida parapsilosis, or Candida guilliermondii. No kill-times
      were achieved with the SNG-containing mouthrinse. These results suggest that
      mouthrinses containing antimicrobial agents might represent an appropriate
      alternative to conventional antifungal drugs in the management of oral
      candidiasis. However, the effectiveness of antimicrobial mouthrinses as
      antifungal agents needs to be evaluated in further clinical trials.

PMID- 9287063
TI  - A comparison of IgG antibody reactive with Bacteroides forsythus and
      Porphyromonas gingivalis in adult and early-onset periodontitis.
AB  - Recent work has indicated that Bacteroides forsythus and Porphyromonas gingivalis
      are significant local risk factors for periodontitis. Several reports find that
      both organisms are frequently associated with periodontitis lesions and often are
      present together. We have previously shown that early-onset periodontitis
      patients seropositive for P. gingivalis have less attachment loss than
      seronegative patients. In this study, we determined serum IgG antibody
      concentrations reactive with B. forsythus in adult and early-onset periodontitis
      patients using an ELISA and used P. gingivalis in the same populations as a
      positive control. The results for P. gingivalis were consistent with previous
      work and indicated that 47%, 36%, and 33% of adult, generalized early-onset, and
      localized juvenile patients were seropositive, respectively. Mean serum IgG
      concentrations for the three groups were 5.36 microg/ml, 5.65 microg/ml, and 5.44
      microg/ml for adult, generalized early-onset, and localized juvenile patients,
      respectively. In contrast, for B. forsythus only 11%, 14%, and 10% of adult,
      generalized early-onset, and localized juvenile patients were seropositive, with
      mean serum IgG concentrations of 0.46 microg/ml, 0.46 microg/ml, and 0.47
      microg/ml, respectively. This suggests that B. forsythus is either poorly
      immunogenic or less invasive than P. gingivalis. If most patients fail to mount
      an immune response to B. forsythus and it is invasive, it may explain why this
      organism is a risk factor for disease.

PMID- 9287064
TI  - The effects of different tetracyclines on the dentin root surface of
      instrumented, periodontally involved human teeth: a comparative scanning electron
      microscope study.
AB  - This in vitro study compares, by scanning electron microscope (SEM) examination,
      the surface effects of various topical applications of tetracycline on the
      instrumented dentin root surface of human teeth. Eighty-two (82) dentin samples
      were prepared from periodontally-compromised teeth planned for extraction.
      Solutions of tetracycline HCl, doxycycline, minocycline, sumycin, and a saline
      control were prepared and applied to the dentin samples for 0.5, 1, 3, 5, and 10
      minutes. Each solution pH was measured: tetracycline HCI (pH 1.6), doxycycline
      (pH 2.2), minocycline (pH 3.8), sumycin (pH 4.4), and saline (pH 5.1). A
      tetracycline periodontal fiber was also evaluated at 1, 4, 7, and 10 days of
      exposure for dentin surface effects. Tetracycline HCI removed the dentin smear
      layer leaving clean and open tubules significantly better than other solutions
      tested in as little as 30 seconds. Doxycycline and minocycline produced similar
      results to each other, which were significantly better than sumycin and saline,
      but not as effective as tetracycline HCl. Smear layer removal was attained by
      doxycycline and minocycline in five to ten minutes; however, sumycin and the
      saline control ineffectively removed the surface smear layer and dentinal tubules
      remained partially to totally occluded by debris. The periodontal fiber did not
      significantly alter the surface smear layer. Results of this study suggest that
      tetracycline HCl is the best current tetracycline form for root surface
      conditioning as measured by its ability to affect both dentin smear layer removal
      and dentin tubule exposure.

PMID- 9287065
TI  - A mucosal irritancy test device for intraoral use in dogs.
AB  - The objective of this investigation was to conduct, in dogs, a 6-hour acute
      mucosal irritation study of a new bioerodible treatment. The main problem was to
      retain the test drug in situ without extraneous irritation from the retention
      device. A buccal cup was machined from acrylic with a chamber capacity of 0.025
      ml and a flange that could be ligated to a tooth. Ten female retired breeder
      beagles, 7 to 8 years old, with naturally occurring moderate periodontitis were
      examined and the upper canine teeth scaled to remove plaque and calculus. One
      week later the buccal cups were placed at the gingival margin of the upper canine
      teeth and fixed in place with wire ligature passing through holes in the flange
      and around the tooth, engaging shallow nicks made in the enamel near the gingival
      margin so the wire would not slide up and down. The buccal cup was further
      stabilized with glass ionomer cement placed on the crown and over the outer
      surface of the cup. Buccal cups were loaded with test, placebo, or no ointment by
      technicians in a scheme to which examiners were blind. Hourly examinations were
      made, and after 6 hours the cups were removed and gingival mucosa scored for
      irritation by a previously described method. All dogs tolerated the test and
      retained the cups for 6 hours. There was no mucosal irritation from the empty
      cups. We conclude that this new device can be used successfully for testing new
      agents for short-term mucosal irritancy.

PMID- 9287066
TI  - Migration of gingival fibroblasts on fibronectin and laminin.
AB  - The migrational behavior of fibroblasts is critical for the maintenance and
      healing of the periodontium. The purpose of this study was to determine, in
      vitro, the differences found in gingival fibroblast migration on the following
      substrates: fibronectin, laminin, bovine serum albumin (BSA), or plastic. Filter
      paper strips soaked in solutions of the test molecules were placed in 35 mm
      culture dishes. Equimolar amounts of the various proteins were allowed to dry
      onto the plastic in a discrete band. The bands were masked and 5.0 x 10(4) cells
      seeded. Rat gingival fibroblasts were allowed to attach for 1.5 hours and the
      protein bands uncovered and incubation continued for 24 hours under standard
      conditions. Cells were fixed, stained and cell images captured, computer
      digitized and migrational areas and cell numbers and areas quantified after
      converting pixels to microm. Cell migration was enhanced on fibronectin
      substrates. Statistically significant differences (P < 0.01) were found for total
      area covered (fibronectin, mean = 110.8 mm2 vs. controls: plastic, mean = 28.2
      mm2; BSA, mean = 18.2 mm2) and the number of cells migrating as compared to
      controls (fibronectin, mean = 1184 vs. controls: plastic, mean = 304, BSA, mean =
      230). No significant differences in area covered or numbers of cells migrating
      were found between controls and cells exposed to other substrates. Mean spread
      area per cell was not statistically significantly different for any of the
      conditions. Numbers of cells migrating on substrates other than fibronectin were
      reduced even more when protein synthesis was inhibited using cycloheximide. In
      this system fibronectin serves as a cue to recruit significantly greater numbers
      of fibroblasts to migrate for greater distances than the other molecules tested.

PMID- 9287067
TI  - Spontaneous bony exposure: a report of 4 cases of idiopathic exposure and
      sequestration of alveolar bone.
AB  - This paper describes 4 cases of spontaneous exposure and sequestration of
      alveolar bone. While one case was associated with an allergic mucositis, the
      other three were idiopathic involving large lingual exostoses.

PMID- 9287068
TI  - Carbon dioxide laser for de-epithelialization of periodontal flaps.
AB  - Regeneration of mineralized and soft connective tissue components of the
      attachment apparatus is the main goal in the treatment of periodontal diseases.
      Often, apical migration of epithelium (long junctional epithelium) effectively
      prevents the formation of bone and connective tissue attachment after periodontal
      surgery. The purpose of the present study was to compare conventional periodontal
      surgery combined with carbon dioxide laser and conventional periodontal surgery
      alone with respect to epithelial elimination and degree of necrosis of
      mucoperiosteal flaps. After signing a consent form, five patients with at least
      two comparable bilateral periodontal defects needing pocket elimination surgery
      participated in this study. The investigators randomly divided each side into
      test and control sites. Each patient received oral hygiene instruction and
      initial therapy prior to surgery. At surgery, the test site received a sulcular
      incision and carbon dioxide laser de-epithelialization of the outer and inner
      aspects of the flap. The control group received reverse bevel incision only. The
      surgeon performed open flap debridement on all teeth. At the time of surgery, the
      surgeon did a biopsy of each site and submitted specimens for histologic
      evaluation. A matched pairs t-test was used to analyze the data. The results show
      significant differences between the carbon dioxide laser and reverse bevel
      incision with respect to sulcular (P < or = 0.025) and gingival (external) (P <
      or = 0.01) flap surface epithelial elimination and tissue necrosis (P < or =
      0.005). These results should be replicated with a larger number of subjects. The
      carbon dioxide laser eliminated sulcular and gingival (external) epithelium
      without disturbing underlying connective tissue. This finding supports the
      concept that the carbon dioxide wavelength has little or no effect on tissues
      beyond the target. However, neither laser nor blade eliminated all the
      epithelium. Researchers observed chronic inflammation in the control and test
      sites, with a predominance of plasma cells. Lining the sulcular and gingival
      (external) lased areas, investigators found coagulation necrosis covered by
      fibrin and coagulated blood. The laser appears to effectively remove epithelium
      at the time of surgery; however, future long-term, well-controlled quantitative
      histologic studies are needed to evaluate the effect of repeated carbon dioxide
      laser de-epithelialization of the gingival (external) surface of mucoperiosteal
      flaps at intervals during the healing period.

PMID- 9287069
TI  - Development and clinical evaluation of a root coverage procedure using a collagen
      barrier membrane.
AB  - The use of guided tissue regeneration (GTR) procedures in the treatment of
      gingival recession has shown promising results and is gaining clinical
      acceptance. The purpose of this study was to assess the use of a bioabsorbable
      collagen membrane as a barrier device in root coverage treatment of gingival
      recession defects. The study consisted of 10 patients with 10 defects of either
      Miller Class I or II description and gingival recession > or =2.5 mm. Clinical
      measurements taken at baseline included plaque index (PI) and gingival index
      (GI), clinical attachment level (CAL) measured with an automated probe and
      reference stent, recession depth (RD; mean = 3.19 +/- 0.26 mm), recession width
      (RW; 3.95 +/- 0.41 mm), probing depth (PD; 2.3 +/- 0.2 mm), and width of
      keratinized tissue (KT; 2.4 +/- 0.3 mm); measurements were repeated at 1, 2, and
      4 weeks and 3 and 6 months post-treatment. During the surgical procedure, a
      mucoperiosteal flap was elevated and the respective root thoroughly planed. The
      collagen membrane was cut to cover the defect and surrounding bone, positioned
      over the root, and secured with 5-0 gut interdental sutures. The flap was
      coronally positioned to cover the membrane and sutured with 5-0 silk. Data were
      analyzed using the Student paired t-test to compare pre- and postsurgery
      measurements. The nonparametric Wilcoxon matched pairs test was used to analyze
      the significance of PI and GI at different time intervals. A statistically
      significant (P < 0.01) reduction in RD (-1.66 +/- 0.25 mm) was observed at 6
      months, representing 51.6% total attainable root coverage. Clinically, a
      statistically significant mean gain of 1.34 +/- 0.47 mm CAL and 0.90 +/- 0.32 mm
      KT was observed at 6 months. No statistical differences were found in PD and RW
      between baseline and 6 months postoperatively. PI and GI remained low and showed
      no statistically significant change (P < 0.05) throughout the study period.
      Results from this study suggest that a collagen membrane can be used successfully
      as a barrier device in GTR-based root coverage procedures.

PMID- 9287070
TI  - A comparative study of root coverage obtained with guided tissue regeneration
      utilizing a bioabsorbable membrane versus the connective tissue with partial
      thickness double pedicle graft.
AB  - Obtaining predictable root coverage has become an important part of periodontal
      therapy. The purpose of this study was to compare two techniques of obtaining
      root coverage. The two techniques were the connective tissue with partial
      thickness double pedicle graft and guided tissue regeneration with a
      bioabsorbable polylactic acid softened with citric acid ester membrane. The
      connective tissue with partial-thickness double pedicle graft had a mean root
      coverage of 97.1%, and the guided tissue regeneration procedure produced a mean
      root coverage of 75.1%. This difference was not statistically significant.
      Additionally, it was the goal of this study to determine if the thickness of the
      tissue near the defect was a factor in root coverage. Thickness of the tissue was
      not a factor with the connective tissue with partial-thickness double pedicle
      graft. The thin areas had a mean root coverage of 100%, while the others had a
      mean root coverage of 95.9%. This difference was not statistically significant;
      however, the thickness of the tissue was a factor in root coverage success in the
      guided tissue regeneration procedure. The thin areas treated with guided tissue
      regeneration had a mean root coverage of 26.7%, while the others had a mean root
      coverage of 95.9%. This difference was statistically significant. The results of
      this study demonstrate that root coverage is possible with both procedures.
      However, when the tissue in the area of the defect is relatively thin, the
      connective tissue with partial-thickness double pedicle graft will produce
      greater root coverage. When treating defects with tissue that is not thin,
      similar amounts of root coverage can be obtained with both procedures.

PMID- 9287071
TI  - Periodontal considerations in the management of the cancer patient. Committee on
      Research, Science and Therapy of the American Academy of Periodontology.
AB  - This position paper on periodontal considerations in the management of the cancer
      patient was prepared by the Research, Science and Therapy Committee of The
      American Academy of Periodontology. It is intended to provide information
      regarding the effects of head and neck radiation, total body radiation,
      chemotherapy, and bone marrow transplantation on the oral tissues. In addition,
      the paper offers suggestions for the prevention and treatment of periodontal and
      oral side effects of cancer therapy. Reliance on this position paper for patient
      management will not guarantee a successful outcome. Cancer therapy may be
      associated with complex problems. Ultimately, decisions regarding the diagnosis
      and treatment of oral disease in an individual patient must be made by the
      treating practitioner in light of the specific facts presented by that patient
      and in consultation with the patient's physician.

PMID- 9287072
TI  - Re: Prevalence of periodontal disease.

PMID- 9287074
TI  - Re: Ability of commercial demineralized freeze-dried bone allograft to induce new
      bone formation (1996;67:918-926)

PMID- 9287073
TI  - Re: Ability of commercial demineralized freeze-dried bone allograft to induce new
      bone formation (1996;67:918-26)

PMID- 9287075
TI  - Effects of radiofrequency versus neurotoxic cingulate lesions on spatial reversal
      learning in mice.
AB  - Mice with radiofrequency (RF) lesions of the posterior (PC) or anterior (AC)
      cingulate cortex were trained on spatial discrimination reversal learning in a T
      maze. The results were compared with those obtained in an earlier study after
      ibotenic acid (IBO) cingulate lesions. PC-RF lesions facilitated the initial
      discrimination and first reversal, whereas they retarded subsequent reversals; in
      contrast, PC-IBO lesions yielded a deficit on the initial discrimination and
      first reversal, but had no effect on subsequent reversals. AC-IBO, but not AC-RF
      lesions, precluded the formation of a learning set across reversals. These data
      suggest that cingulum transection, which accompanies RF but not IBO lesions, can
      mask or even antagonize the specific effects of cingulate damage. Consequently,
      inferences made from the effects of conventional lesions to assess and
      distinguish the functions of the two cingulate areas appear subject to caution.

PMID- 9287077
TI  - Systematic comparison of the effects of hippocampal and fornix-fimbria lesions on
      acquisition of three configural discriminations.
AB  - The effects of lesions to the hippocampal system on acquisition of three
      different configural tasks by rats were tested. Lesions of either the hippocampus
      (kainic acid/colchicine) or fornix-fimbria (radiofrequency current) were made
      before training. After recovery from surgery, rats were trained to discriminate
      between simple and compound-configural cues that signaled the availability or
      nonavailability of food when a bar was pressed. When positive cues were present,
      one food pellet could be earned by pressing a lever after a variable time had
      elapsed. The trial terminated on food delivery (variable interval 15 s). This
      procedure eliminates some possible alternative explanations of the results of
      previous experiments on configural learning. Hippocampal lesions increased rates
      of responding and retarded acquisition of a negative patterning task (A+, B+, AB
      ); using a ratio measure of discrimination performance these lesions had a milder
      retarding effect on a biconditional discrimination (AX+, AY-, BY+, BX-), and they
      had no effect on a conditional context discrimination (X: A+, B-; Y: A-, B+).
      Fornix-fimbria lesions did not affect acquisition of any of these tasks but
      increased rates of responding. The results suggest that several task parameters
      determine the involvement of the hippocampus in configural learning; however, all
      tasks tested can also be learned to some extent in the absence of an intact
      hippocampal system, presumably by other learning/memory systems that remain
      intact following surgery. The lack of effect of fornix-fimbria lesions on any of
      these tasks suggests that retrohippocampal connections with other brain areas may
      mediate hippocampal contributions to the learning of some configural tasks. An
      analysis of these results and of experiments on spatial learning situations
      suggests that involvement of the hippocampus is a function of the degree to which
      correct performance depends on a knowledge of relationships among cues in a
      situation.

PMID- 9287078
TI  - Current source density analysis of the potential evoked in hippocampus by
      perirhinal cortex stimulation.
AB  - Previous anatomical research has demonstrated that the perirhinal cortex (PRC)
      projects to the dorsal hippocampal CA1 field. We have recently presented data
      (Liu and Bilkey, Hippocampus 1996; 6:125-135) which suggests that this pathway
      courses via the lateral perforant path (LPP). In the present study, laminar
      profiles of the average evoked potentials and current source density (CSD)
      analysis were used to study the input from the perirhinal cortex to the dorsal
      hippocampus in the urethane-anaesthetized rat. Stimulation of the lateral
      perforant path activated a current sink in the stratum lacunosum-moleculare of
      CA1 and the outer molecular layer of the dentate gyrus with an onset latency of
      3.5 ms. Stimulation of the perirhinal cortex produced a very similar sink-source
      pattern with an onset latency of 4.0 ms. Higher-intensity stimulation of lateral
      entorhinal cortex also produced a similar pattern with an onset latency of 4.5
      ms. Electrolytic lesions of PRC conducted 4-5 days prior to testing resulted in a
      major decrease (58%) in the amplitude of the LPP-elicited potentials and a
      corresponding reduction across the whole source-sink pattern. A similar result
      was observed following ibotenic acid lesions of PRC. In contrast, similar-sized
      electrolytic lesions of lateral entorhinal cortex produced a much smaller (16%)
      decrease in potential amplitude and little change in the source-sink pattern.
      These data provide further support for the hypothesis that perirhinal cortex
      projects to both the dentate gyrus and CA1 regions of the hippocampus via the
      lateral perforant path.

PMID- 9287076
TI  - Perseveration on place reversals in spatial swimming pool tasks: further evidence
      for place learning in hippocampal rats.
AB  - Animals with damage to the fimbria-fornix (FF) or cells of the hippocampus (HIP)
      can learn a place problem but cannot learn matching-to-place problems, which
      feature a series of place "reversals." The two experiments described in the
      present report were designed to examine the causes of impairment on reversal
      learning. In experiment 1, control, HIP, and FF groups were trained to asymptote
      on a place problem, and then the location of the platform was moved. Control rats
      learned the reversal response more quickly than the initial response; the HIP
      rats learned both problems at the same rate. Swim analysis showed that the
      impairment in the lesion group on the reversal response was aggravated by
      perseverative returns to the first learned place. In experiment 2, control and FF
      groups were trained on a task in which the platform was visible on three daily
      trials and hidden on one daily trial. After 10 days, the platforms were moved. In
      the reversal response, the FF group showed enhanced performance on the cue trials
      and severely impaired performance on the place trials relative to initial
      learning and control performance. Swim analysis showed that FF rats perseverated
      on the initial place response in place trials. These experiments provide further
      evidence for place learning in hippocampal rats and show that perseverative
      responses contribute to impairments in new learning. The results are discussed in
      relation to the idea that the hippocampus mediates spatial mapping and/or uses
      self-movement cues to solve spatial problems.

PMID- 9287079
TI  - Collateral projections from the rat hippocampal formation to the lateral and
      medial prefrontal cortex.
AB  - Projections from the hippocampal formation to the medial prefrontal cortex are
      well known. In this report we used two retrogradely transported tracers to show
      that a small but significant subpopulation of pyramidal neurons in area CA1 and
      subiculum of the hippocampal formation projects to the lateral prefrontal cortex.
      About half of these neurons also possess collateral projections to the medial
      prefrontal cortex. The neurons projecting only to the lateral PFC are found in
      the intermediate hippocampal formation and in the most ventral part of the
      temporal subdivision. On the other hand, most of the neurons projecting to the
      medial prefrontal cortex only are present in the temporal and ventral
      intermediate hippocampal formation, and their number decreases in the dorsal
      intermediate subdivision. The distribution of neurons having collateral
      projections is comparable to that of neurons projecting to the medial prefrontal
      cortex only. In view of proposed functional differences between the septal one
      third and the temporal two-third of the hippocampal formation, it is of interest
      that the neurons projecting to the prefrontal cortex are only present in the
      temporal two-thirds.

PMID- 9287080
TI  - Neonatal hippocampal damage in rats: long-term spatial memory deficits and
      associations with magnitude of hippocampal damage.
AB  - This study investigated the effects of neonatal hippocampal ablation on the
      development of spatial learning and memory abilities in rats. Newborn rats
      sustained bilateral electrolytic lesions of the hippocampus or were sham-operated
      on postnatal day 1 (PN1). At PN20-25, PN50-55, or PN90-95, separate groups of
      rats were tested in a Morris water maze on a visible "cue" condition (visible
      platform in a fixed location of the maze), a spatial "place" condition (submerged
      platform in a fixed location), or a no-contingency "random" condition (submerged
      platform in a random location). Rats were tested for 6 consecutive days, with 12
      acquisition trials and 1 retention (probe) trial per day. During acquisition
      trials, the rat's latency to escape the maze was recorded. During retention
      trials (last trial for each day, no escape platform available), the total time
      the rat spent in the probe quadrant was recorded. Data from rats with hippocampal
      lesions tested as infants (PN20-25) or as adults (PN50-55 and PN90-95) converged
      across measures to reveal that 1) spatial (place) memory deficits were evident
      throughout developmental testing, suggesting that the deficits in spatial memory
      were long-lasting, if not permanent, and 2) behavioral performance measures under
      the spatial (place) condition were significantly correlated with total volume of
      hippocampal tissue damage, and with volume of damage to the right and anterior
      hippocampal regions. These results support the hypothesis that hippocampal
      integrity is important for the normal development of spatial learning and memory
      functions, and show that other brain structures do not assume hippocampal-spatial
      memory functions when the hippocampus is damaged during the neonatal period (even
      when testing is not begun until adulthood). Thus, neonatal hippocampal damage in
      rats may serve as a rodent model for assessing treatment strategies (e.g.,
      pharmacological) relevant to human perinatal brain injury and developmental
      disabilities within the learning and memory realm.

PMID- 9287081
TI  - Stimulus-dependent induction of long-term potentiation in CA1 area of the
      hippocampus: experiment and model.
AB  - In the CA1 area of the hippocampus, the magnitude of long-term potentiation (LTP)
      depends not only on the frequency of applied stimuli, but also on their number.
      With a slice preparation using extracellular recording in the hippocampus CA1 of
      a guinea pig, we investigate the magnitude of LTP induced by electrical stimuli
      with a range of frequencies and the number of applied stimuli. We find that the
      magnitude of the saturated potentiation obtained with periodic stimuli largely
      depends on the frequency and is insensitive to the number of stimuli, once the
      saturation level has been obtained. Furthermore, we investigated nonperiodic
      stimuli and found that the magnitude of the saturated potentiation is also
      sensitive to the statistical correlation between successive interstimulus
      intervals, even when their average frequency is held constant. In order to
      explain the LTP dependence on these various experimental parameters, we propose a
      simple mathematical model for the induction of LTP. In the model, an
      exponentially decaying element released as a result of previous stimuli is
      coupled with a new stimulus to act as the potentiation force, and the magnitude
      of potentiation is determined by this potentiation force. We can determine the
      decaying time constant of this hypothetical element as a model parameter by
      fitting the model to the experimental data. The time scale is found to be of the
      order of 200 msc. A molecular or cellular factor with this decaying time constant
      is likely to be induced in LTP induction.

PMID- 9287082
TI  - Exposure to chronic psychosocial stress and corticosterone in the rat: effects on
      spatial discrimination learning and hippocampal protein kinase Cgamma
      immunoreactivity.
AB  - Previous reports have demonstrated a striking increase of the immunoreactivity of
      the gamma-isoform of protein kinase C (PKCgamma-ir) in Ammon's horn and dentate
      gyrus (DG) of rodent hippocampus after training in a spatial orientation task. In
      the present study, we investigated how 8 days of psychosocial stress affects
      spatial discrimination learning in a hole board and influences PKCgamma-ir in the
      hippocampal formation. The acquisition of both reference memory and working
      memory was significantly delayed in the stressed animals during the entire
      training period. With respect to cellular plasticity, the training experience in
      both nonstressed and stressed groups yielded enhanced PKCgamma-ir in the CA1 and
      CA3 regions of the posterior hippocampus but not in subfields of the anterior
      hippocampus. Stress enhanced PKCgamma-ir in the DG and CA3 pyramidal cells of the
      anterior hippocampus. In stressed animals that were subsequently trained, the
      PKCgamma-ir was increased in the posterior CA1 region to the same level as that
      found in nonstressed trained animals. Stress apparently abrogated the PKCgamma-ir
      training response in the CA3 region. In a second experiment, the elevation of
      plasma corticosterone levels to values that are found during stress did not
      significantly influence reference memory scores but slightly and temporarily
      affected working memory. The training-induced enhancement of PKCgamma-ir in the
      CA1 region was similar in trained and corticosterone-treated trained animals, but
      the learning-induced PKCgamma-ir response in the posterior CA3 area was absent
      after corticosterone pretreatment. These results reveal that prolonged
      psychosocial stress causes spatial learning deficits, whereas artificial
      elevation of corticosterone levels to the levels that occur during stress only
      mildly affects spatial memory performance. The spatial learning deficits
      following stress are reflected only in part in the redistribution of hippocampal
      PKCgamma-ir following training.

PMID- 9287084
TI  - Radionuclides in the body: meeting the challenge. Lauriston S. Taylor Lecture.

PMID- 9287083
TI  - Feed-forward and feed-back activation of the dentate gyrus in vivo during dentate
      spikes and sharp wave bursts.
AB  - Intermittently occurring field events, dentate spikes (DS), and sharp waves (SPW)
      in the hippocampus reflect population synchrony of principal cells and
      interneurons along the entorhinal cortex-hippocampus axis. We have investigated
      the cellular-synaptic generation of DSs and SPWs by intracellular recording from
      granule cells, pyramidal cells, and interneurons in anesthetized rats. The
      recorded neurons were anatomically identified by intracellular injection of
      biocytin. Extracellular recording electrodes were placed in the hilus to record
      field DSs and multiple units and in the CA1 pyramidal cell layer to monitor SPW
      associated fast field oscillations (ripples) and unit activity. DSs were
      associated with large depolarizing potentials in granule cells, but they rarely
      discharged action potentials. When they were depolarized slightly with
      intracellular current injection, bursts of action potentials occurred
      concurrently with extracellularly recorded DSs. Two interneurons in the hilar
      region were also found to discharge preferentially with DSs. In contrast, CA1
      pyramidal cells, recorded extracellularly and intracellularly, were suppressed
      during DSs. In association with field SPWs, extracellular recordings from the CA1
      pyramidal layer and the hilar region revealed synchronous bursting of these cell
      populations. Intracellular recordings from CA3 and CA1 pyramidal cells, granule
      cells, and from a single CA3 region interneuron revealed SPW-concurrent
      depolarizing potentials and action potentials. These findings suggest that
      granule cells may be discharged anterogradely by entorhinal input or retrogradely
      by the CA3-mossy cell feedback pathway during DSs and SPWs, respectively.
      Although both of these intermittent population patterns can activate granule
      cells, the impact of DSs and SPWs is diametrically opposite on the rest of the
      hippocampal circuitry. Entorhinal cortex activation of the granule cells during
      DSs induces a transient decrease in the hippocampal output, whereas during SPW
      bursts every principal cell population of the hippocampal formation may be
      recruited into the population event.

PMID- 9287085
TI  - Summary and evaluation of guidelines for occupational exposure to power frequency
      electric and magnetic fields.
AB  - Major U.S. and international guidelines for limiting occupational exposures to
      EMF are evaluated. These safety guidelines are designed to prevent short-term
      adverse effects by maintaining bulk-tissue current densities below 10 mA m(-2)
      (rms). Above this level, effects of induced currents and electric fields can
      include stimulation of neural and cardiac tissues. The models and input data used
      by guideline-setting organizations to relate 50/60-Hz magnetic-field exposures to
      induced current densities differ significantly. In order to develop a better
      understanding of such differences, the current densities derived from exposure
      guideline models are compared to minimum thresholds for cardiac stimulation and
      fibrillation. The nominal minimum thresholds for cardiac stimulation and
      ventricular fibrillation are 100 times and 200 times greater, respectively, than
      the current density of 10 mA m(-2) used as a dosimetric limit. However, the
      assumed relationship between the 10 mA m(-2) dose limit and magnetic field
      exposure limits introduces additional uncertainty. The ratios between the
      threshold for cardiac stimulation and the calculated induced current density at
      the exposure limit vary between a low of 50 and a high of 526, depending upon the
      guideline. These ratios, as indicators of implicit safety factors, are larger
      than those recommended to protect against adverse effects of induced current
      density, including cardiac stimulation, in magnetic resonance imaging or against
      adverse effects of toxic chemical exposures. This review and assessment of EMF
      occupational exposure guidelines suggests that several scientific and compliance
      issues remain ambiguous or unresolved. Recommendations are made for guideline
      organizations to strengthen and clarify the scientific basis for the guideline
      process. These recommendations include the documentation of supporting data,
      development of operational definitions for guidelines, examination of dosimetric
      models, clarification of safety factors, and identification of high priority
      topics for future research.

PMID- 9287086
TI  - UV protection by clothing: an intercomparison of measurements and methods.
AB  - In an attempt to reduce the incidence of skin cancer, cancer foundations have run
      educational campaigns which encourage the general population to limit their solar
      UVR exposures. An important part of these campaigns, in particular in Australia,
      but also more recently in Europe and the U.S., has been the adoption of
      protective measures such as sunscreens, hats, sunglasses and clothing. The
      protective properties of fabrics and clothing against ultraviolet radiation (UVR)
      have been known for some time, but recently there has been considerable interest
      in quantifying the degree of protection. This has been generated, in part, by the
      requirements for occupational protection for outdoor workers as well as the
      provision of UVR protection for the recreational market. The quantification of
      UVR protection has been laboratory based using in vitro test methods. Development
      of a standard test method has become an important part of the testing process,
      and this paper presents results from an intercomparison involving five
      independent testing laboratories. Agreement is good, in particular for samples
      with protection factors below 50. Technical difficulties and sources of errors
      associated with the measurements are discussed.

PMID- 9287087
TI  - 60Co contamination in recycled steel resulting in elevated civilian radiation
      doses: causes and challenges.
AB  - Since late 1992, more than 100 building complexes containing public and private
      schools and nearly 1,000 apartments have been identified in Taiwan with elevated
      levels of gamma-radiation from construction steel contaminated with 60Co. Due to
      improper handling of 60Co contaminated scrap steel in late 1982 and 1983,
      contaminated construction materials have been widely distributed throughout the
      country. These contaminated construction materials have generated elevated
      radiation exposures to members of the public in Taiwan. As of early 1996, more
      than 4,000 people, including young students, have been identified as receiving
      more than 1 mSv y(-1) above the local background for up to 12 y. This report
      provides a detailed discussion of the sources of the 60Co contamination in
      construction steel, its discovery in the building complexes, and preliminary
      evaluation and remediation activities.

PMID- 9287088
TI  - Fundamentals for establishing a risk communication program.
AB  - This paper provides a suggested outline for developing a risk communication
      organizational plan that could be used by a variety of federal, state, or private
      agencies. Drawing on various techniques presented in the literature and on the
      authors' insights, suggestions are provided as to how to formulate and convey
      risk messages. First, the paper provides a few risk communication fundamentals
      including definitions, the goal of informing vs. influencing, the importance of
      public participation in risk management, building trust and credibility, the
      consideration of outrage, and the importance of oral and visual communications.
      Second, a stepwise approach synthesized by the authors is presented that can be
      applied in developing a risk communication program. The approach is a 13-step
      method based on the premise that the risk communication program should be
      dynamic, flexible, and involve interaction with the public at every possible
      step.

PMID- 9287089
TI  - Temperature response of two photographic films and TLDs suitable for patient
      dosimetry of high dose fluoroscopic procedures.
AB  - When making direct measurements of skin entrance dose for patients undergoing
      interventional x-ray procedures the dosimeter may be placed near or in direct
      contact with the skin. The response of such dosimeters to heating during x-ray
      exposure must be known for accurate dosimetry. Two photographic films and MgB4O7
      TLDs used for patient dose monitoring were exposed under different temperature
      conditions. Film dose response curves were obtained at room temperature and body
      temperature (22 degrees C and 38 degrees C). The TLD response at room and body
      temperature was also checked at 14 Gy. Dose response curves of FGP film show at
      most a 22+/-2% increase in predicted dose at 37 degrees C in the range of 0.3 to
      2.8 Gy. LOC4 film showed less than a 2% difference in response between 22 and 37
      degrees C over a range of 1 to 11 Gy. The TLDs showed less than a 2% difference
      at a dose of 14 Gy. Uncertainty in skin dose estimation is less than 2% using
      LOC4 film and MgB4O7 TLD arrays. Uncertainty in temperature during exposure of
      Kodak fine grain positive film may lead to errors in dose estimates of +/-11%.
      Arrays of TLDs and copy film are more suitable for measurements of high doses and
      are less sensitive to temperature changes during exposure than the fine grain
      film.

PMID- 9287091
TI  - A new device to measure the activity size distribution of radon progeny in a low
      level environment.
AB  - In order to easily measure the activity size distribution of radon progeny, a new
      instrument was developed that can determine their activity median diameter in a
      low level environment within 90 min. A four stage low-pressure cascade impactor
      was used. The particle size cut-off points were >2,100, 700, 210 and 70 nm, based
      on a particle density of 1 g cm(-3). A 300 metal wire screen diffusion collector
      facing with a silicon semiconductor detector was placed within the first air
      inlet in order to measure unattached radon progeny concentrations and also to
      prevent unattached progeny from entering the impactor. Silicon photodiodes, from
      which the ceramic windows were removed, were installed in each stage of the
      impactor. Alpha particles could be effectively detected with 46.2% efficiency as
      radon progeny were directly collected on the detecting surface of the photodiode.
      The surface of the photodiodes was coated with silicon grease to prevent particle
      bounce-off. An inline-type filter holder with a silicon semiconductor detector
      was connected at the exit of the impactor in order to collect the remaining radon
      progeny and to measure their concentrations. The instrument was used to
      concurrently measure the size distribution of radon progeny and the aerosol in
      the natural environment. The results indicated that the activity median diameter
      fell in between the median diameter of the aerosol derived from number statistics
      and that derived from surface-area statistics. A negative correlation was found
      between the unattached fraction (f(p)) and the activity median diameter.

PMID- 9287090
TI  - Non-linear radionuclide transfer from the aquatic environment to fish.
AB  - Uptake of 226Ra, 232Th, 230Th, and 228Th from water, sediment, and diet sources
      to bone and muscle of white suckers (Catostomus commersoni) was studied in
      sixteen lakes in the uranium-mining district of Ontario, Canada. Fish tissues did
      not increase linearly with environmental concentrations. The best relationship
      appears to be a power function. This has implications for the accuracy of
      radiological dose and risk estimates for uranium mining impacts, which are often
      based on a linear model.

PMID- 9287092
TI  - 137Cs urinary excretion by northwestern Italians ten years after the Chernobyl
      accident.
AB  - Measurements of 137Cs contamination in the urine of 37 individuals were performed
      in 1995 and 1996 in order to evaluate the 137Cs daily urinary excretion in the
      northwestern italian people ten years from the Chernobyl accident. The difference
      between the average 137Cs daily urinary excretion assessed for 1995 and for 1996
      was not statistically significant. Using the values of urine contamination, an
      estimate of 0.2 Bq(-1) of mean ingested activity was obtained. A mean committed
      effective dose of about 1 microSv was determined as due to the 137Cs ingestion
      during 1 y at 10 y after the accident. Such a dose is lower by a factor of 10(3)
      than the corresponding value for the population of North Italy in the first year
      following the Chernobyl accident.

PMID- 9287093
TI  - Carbon cartridge standards for 125I and suggested applications.
AB  - Carbon cartridge standards were prepared to assess the activity of 125I incident
      on, and adsorbed in, cartridge samples during air sampling. Each cartridge
      standard consisted of an 125I-spiked filter paper at a known depth, ranging from
      0 to 19 mm, embedded in approximately 34 g of 20-30 mesh activated carbon
      contained within a 6.35 cm diameter by 2.22 cm deep metal cartridge with screened
      openings. The total counting efficiency values range from 17.8 to 20.8% for
      cartridges counted at 3.2 mm from a thin-crystal NaI(Tl) detector. The standards
      were analyzed using a front/back counting technique, and fitting functions were
      developed relating the front/back net counts ratio and counting efficiency to the
      125I depth of burial. A method for determining sample activity that accounts for
      exponential radioiodine loading in cartridge samples is compared to a less
      complicated technique that assumes all the radioiodine is located at an
      equivalent depth of burial that is based on the sample front/back net counts
      ratio. In addition, methods are presented for determining airborne 125I activity
      for constant and variable concentrations. Variable concentrations are assumed to
      occur in a fume hood duct by one or more bulk releases as a result of iodinations
      that are performed during a given sampling interval. The two methods are shown to
      have maximum relative deviations ranging from -16 to +16%.

PMID- 9287094
TI  - Determination of MDA for a two count method for stripping short-lived activity
      out of an air sample.
AB  - When measuring airborne activity of isotopes with very low annual limit of
      intakes, interference from natural radioactivity presents an obstacle to
      obtaining timely results. One method for solving this problem is to perform two
      separate counts of the sample and mathematically strip-out the contribution from
      the short-lived component. While this method can process a large volume of
      samples with little or no preparation time, the sensitivity of the analysis is
      hard to determine. In an attempt to determine the sensitivity of the analysis and
      to quantify the parameters that affect it, an equation for the minimum detectable
      activity was derived. Actual air sample data were then evaluated against this
      equation to determine its usefulness.

PMID- 9287095
TI  - Performance testing of the Eberline RMS-II criticality accident monitor.
AB  - The Plutonium Facility at Los Alamos uses Eberline RMS-II monitors as part of its
      criticality accident alarm system. The monitors are designed to accommodate a
      wide spectrum of criticality accident scenarios from both liquid and metal
      supercriticalities. A series of experiments were performed at the Los Alamos
      Critical Experiments Facility to evaluate the response of the monitor to a wide
      range of radiation transients. The primary objectives of the evaluation were to
      verify reliable and prompt latching of the criticality alarms in accordance with
      the performance criteria of ANSI/ANS-8.3-1986. The RMS-II monitor performed
      reliably during all of the experiments and was found to meet specific ANSI/ANS
      performance criteria for latching.

PMID- 9287096
TI  - Response to Beninson.

PMID- 9287097
TI  - Condensation of Laurie Taylor's 1980 article.

PMID- 9287098
TI  - Environmental radiation dose in Semipalatinsk area near nuclear test site.

PMID- 9287099
TI  - Issues concerning EPA's cost/benefit analyses of radiological cleanup criteria.

PMID- 9287100
TI  - Response to Cohen's plea for help.

PMID- 9287101
TI  - Sex-specific tissue weighting factors.

PMID- 9287102
TI  - Response to Potter.

PMID- 9287103
TI  - Response to C.S. Sims.

PMID- 9287104
TI  - Response to C.S. Sims.

PMID- 9287105
TI  - Guidelines on limits of exposure to broad-band incoherent optical radiation (0.38
      to 3 microM). International Commission on Non-Ionizing Radiation Protection.

PMID- 9287106
TI  - The active site region of the vitamin K-dependent carboxylase includes both the
      amino-terminal hydrophobic and carboxy-terminal hydrophilic domains of the
      protein.
AB  - In order to localize the active site of the vitamin K-dependent carboxylase, we
      developed an affinity probe containing the propeptide and the first two
      carboxylatable glutamate residues conserved in many native substrates. This probe
      crosslinked to both the hydrophobic amino-terminal and hydrophilic carboxy
      terminal domains of the carboxylase, in contrast with previous work which
      localized both the catalytic and the propeptide binding site within the amino
      terminal hydrophobic domain. Amino acid analysis revealed that the mass of an
      amino-terminal fragment is seriously underestimated by SDS-PAGE. Reanalysis of
      the published data in light of this information suggests that a portion of the
      propeptide binding site resides within the carboxy-terminal hydrophilic domain.

PMID- 9287107
TI  - Burdock, a novel retrotransposon in Drosophila melanogaster, integrates into the
      coding region of the cut locus.
AB  - The burdock element is known to be the 2.6-kb insertion into the same region of
      the cut locus in 12 independently obtained ct-lethal mutants. Here we have
      determined the complete sequences of this insertion and of the hot spot region.
      It was found that the burdock is a short retrotransposon with long terminal
      repeats and a single open reading frame (ORF). The polypeptide encoded by the
      burdock ORF contains two adjacent regions homologous to the gag and pol
      polyproteins of the gypsy mobile element. The burdock insertion interrupts the
      short ORF of the cut locus. The target site sequence of the burdock insertions is
      similar to the Drosophila topoisomerase II cleavage site.

PMID- 9287108
TI  - The receptor for urokinase-type plasminogen activator is expressed during mouse
      spermatogenesis.
AB  - Urokinase-type plasminogen activator (uPA) binds to a plasma membrane receptor
      (uPAR) that localizes plasmin generation to the cell environment. Mouse
      spermatozoa have surface-bound uPA, which appears to be acquired from genital
      tract secretions at ejaculation. We determined the presence of uPAR mRNA in
      spermatogenic cells and their uPA-binding activity. Northern blot and in situ
      hybridization demonstrated the presence of uPAR mRNA in germ cells. Binding of
      uPA, but not of a mutant enzyme lacking the receptor-binding domain, indicated
      the presence of uPAR on spermatids and spermatozoa. The uPAR and/or receptor
      bound uPA may be involved in spermatogenesis, spermatozoa maturation or
      fertilization.

PMID- 9287109
TI  - Functional cloning of a cDNA encoding Mei2-like protein from Arabidopsis thaliana
      using a fission yeast pheromone receptor deficient mutant.
AB  - To isolate Arabidopsis cDNAs that encode signal transducers and components
      involved in the regulation of meiosis, a trans-complementation analysis was
      performed using a Schizosaccharomyces pombe meiosis-defective mutant in which the
      genes for pheromone receptors were disabled. One cDNA obtained in this screening
      encodes a polypeptide, named AML1, that shows significant similarity to S. pombe
      Mei2 protein and has three putative RNA-recognition motifs like as Mei2. Mei2 is
      involved in the regulation of meiosis in fission yeast. Northern blot analysis
      showed that the AML1 gene is expressed in each organ. The possible functions of
      AML1 are discussed.

PMID- 9287111
TI  - Expression and subcellular localization of mouse 20S proteasome activator complex
      PA28.
AB  - We have cloned the mouse PA28 proteasome activator cDNAs. Northern blot
      demonstrates high PA28 mRNA levels in liver, kidney and lung. mRNA levels are low
      in thymus, spleen and brain. In contrast, PA28 protein levels vary little between
      these tissues. Immunocytological analysis and cell fractionation experiments
      demonstrate that both subunits are almost equally distributed between the
      cytoplasm and the nucleus. Interestingly, PA28alpha spares nucleoli, while
      PA28beta is strongly enhanced in the nucleolus. This indicates for the first time
      that the PA28alpha and PA28beta subunits may serve nuclear functions which may be
      different from and independent of each other.

PMID- 9287110
TI  - Stromal and thylakoid-bound ascorbate peroxidases are produced by alternative
      splicing in pumpkin.
AB  - A cDNA encoding stromal ascorbate peroxidase (sAPX) was isolated using poly(A)+
      RNA of pumpkin cotyledons by RT-PCR. The cDNA encodes a polypeptide with 372
      amino acids and shares complete sequence identity with pumpkin thylakoid-bound
      ascorbate peroxidase (tAPX), except for the deletion of a putative membrane
      spanning region located in the carboxy domain of tAPX. Southern blot
      hybridization and analysis of intron structure indicated that mRNAs for sAPX and
      tAPX, whose suborganellar localizations in chloroplasts are different, are
      produced by alternative splicing. Immunoblot analysis showed that the
      accumulation of sAPX and tAPX was differently regulated during germination and
      subsequent greening of pumpkin cotyledons.

PMID- 9287112
TI  - Inhibition of gibberellin biosynthesis by nitrate in Gibberella fujikuroi.
AB  - Gibberellin production in Gibberella fujikuroi starts upon exhaustion of the
      nitrogen source. To determine the role of nitrate and ammonium in the regulation
      of gibberellin biosynthesis we have isolated mutants that cannot use nitrate as a
      nitrogen source. Nitrate inhibited partially the production of gibberellins in
      mutants devoid of nitrate reductase activity. The inhibition occurred whether
      nitrate was added before or after the onset of gibberellin production. Addition
      of tungstate to the wild type mimicked the results with nitrate reductase
      mutants. We conclude that nitrate inhibits gibberellin biosynthesis by itself,
      independently of the intracellular signal that conveys nitrogen availability.

PMID- 9287113
TI  - Involvement of 5' flanking sequence for specifying RNA editing sites in plant
      mitochondria.
AB  - Unsuccessful insertion of foreign DNA into plant mitochondrial genomes has
      hindered scientific evaluation of cis-elements needed for RNA editing. Both a
      normal atp6 gene and a chimeric atp6 sequence are present in rice mitochondria.
      The chimeric atp6 contains one-half of the normal atp6 sequence in its 5' portion
      and an unknown sequence in its downstream portion. The C-nucleotide at position
      511, located just upstream of the unknown sequence recombined in the chimeric
      atp6 sequence, is edited, as are other possible editing sites upstream from
      position 511. We report here that the 5' sequence adjacent to the editing site of
      atp6 contains cis-information required for RNA editing and that the 3' sequence
      flanking the editing site provides little contribution to editing-site
      recognition.

PMID- 9287114
TI  - The mouse genome encodes a single homolog of the antimicrobial peptide human beta
      defensin 1.
AB  - The cysteine-rich beta-defensin peptides are broad-spectrum bactericidal agents
      expressed in epithelial and myeloid tissues. The human beta-defensin-1 (hBD-1)
      gene maps adjacent to the human alpha-defensin cluster and is expressed in the
      respiratory, gastrointestinal and genitourinary tracts. Here, we characterize a
      mouse beta-defensin gene (mBD-1) which is: (1) closely related to hBD-1 both in
      sequence and gene organization; (2) expressed at high levels in the mouse kidney
      and at lower levels in brain, heart, lung, uterus, spleen, skeletal muscle,
      stomach, and small intestine; and (3) maps to mouse chromosome 8 at or near the
      location of the mouse alpha-defensin genes. These data indicate that mBD-1 is a
      close homolog of hBD-1, and suggest that analysis of its role in mouse host
      defense may provide significant insights into human epithelial innate immunity.

PMID- 9287115
TI  - A multifunctional protein: involvement of the alpha-1 serum protease inhibitor in
      SDS and high salt-stable DNA-protein complexes.
AB  - Occasionally new and intriguing roles arise for proteins with well established
      functions. The alpha-1 serum protease inhibitor (alpha-1 PI) represents another
      example. Sequence identities exist in the alpha-1 PI and in a nuclear 52-kDa
      glycoprotein which is involved in resistant DNA-polypeptide complexes. The
      results of Western blots support the identity of the two proteins and
      immunocytochemical studies indicate the nuclear location of the alpha-1 PI.
      Consistently, e.g. Ehrlich ascites tumor cells express the alpha-1 PI, and the
      fusion protein between the alpha-1 PI and the green fluorescent protein from
      Aequorea victoria shows intracellular accumulation and partly nuclear location.

PMID- 9287116
TI  - A single mutation at the catalytic site of TF1-alpha3beta3gamma complex switches
      the kinetics of ATP hydrolysis from negative to positive cooperativity.
AB  - Previously, we reported the substitution of Tyr341 of the F1-ATPase beta subunit
      from a thermophilic Bacillus strain PS3 with leucine, cysteine, or alanine (M.
      Odaka et al. J. Biochem., 115 (1994) 789-796). These mutations resulted in a
      great decrease in the affinity of the isolated beta subunit for ATP-Mg and an
      increase in the apparent Km of the alpha3beta3gamma complex in ATP hydrolysis
      when examined above 0.1 mM ATP. Here, we examined the ATPase activity of the
      mutant complexes in a wide range of ATP concentration and found that the mutants
      exhibited apparent positive cooperativity in ATP hydrolysis. This is the first
      clear demonstration that a single mutation in the catalytic sites converts the
      kinetics from apparent negative cooperativity in the wild-type alpha3beta3gamma
      complex to apparent positive cooperativity. The conversion of apparent
      cooperativity could be explained in terms of a simple kinetic scheme based on the
      binding change model proposed by Boyer.

PMID- 9287117
TI  - Trans-activation by the Drosophila myb gene product requires a Drosophila
      homologue of CBP.
AB  - Attempts to demonstrate trans-activation activity by the Drosophila myb gene
      product (D-Myb) have been unsuccessful so far. We demonstrate that co
      transfection of Schneider cells with a plasmid expressing the Drosophila
      homologue of transcriptional co-activator CBP (dCBP) results in transactivation
      by D-Myb. Using this assay system, the functional domains of D-Myb were analyzed.
      Two domains located in the N-proximal region, one of which is required for DNA
      binding and the other for dCBP binding, are both necessary and sufficient for
      trans-activation. In this respect, D-Myb is similar to c-Myb and A-Myb, but
      different from mammalian B-Myb. These results shed light on how the myb gene
      diverged during the course of evolution.

PMID- 9287119
TI  - Identification of a cyclic peptide inhibitor of platelet-derived growth factor-BB
      receptor-binding and mitogen-induced DNA synthesis in human fibroblasts.
AB  - Peptides corresponding to residues from Loops I and III of platelet-derived
      growth factor-BB (PDGF-BB) were examined for their potential to act as PDGF
      antagonists. We have identified two peptides which directly stimulated DNA
      synthesis in human dermal fibroblasts and a cyclic peptide which inhibited PDGF
      induced DNA synthesis. The inhibitory action of cyclic PDGF-BB(73-81), on DNA
      synthesis was shown to be restricted to cells which express PDGF receptors. Also
      cyclic PDGF-BB(73-81) specifically competed for 125I-labelled PDGF-BB but not for
      125I-labelled EGF binding to their respective cellular receptors. The cyclic
      peptide therefore provides a minimum structure to investigate PDGF/receptor
      interactions and our findings confirm the importance of the loop configuration of
      PDGF-BB(73-81) in the native molecule. The cyclic peptide may constitute a basis
      for developing more potent inhibitors of PDGF action.

PMID- 9287118
TI  - pmg-1, a novel gene specifically expressed during the invasive growth phase of
      the mammary gland at puberty.
AB  - The acquisition of invasive properties is a crucial event during carcinogenesis,
      determining the clinical outcome. The mammary gland at puberty provides an ideal
      model for investigating the induction and control of invasive growth. During this
      growth phase, the mammary epithelium participates in a normal, hormonally
      controlled invasive penetration into the stroma. We have applied the differential
      display method to search for genes specifically activated during this
      developmental stage. We have identified and molecularly characterized a novel
      pubertal mammary gland specific gene, pmg-1. This gene is conserved in mammals
      and encodes a protein of 19.9 kDa. Northern blotting and in situ hybridization
      revealed that pmg-1 expression was exquisitely restricted to the epithelium at
      early puberty. To our knowledge this represents the first isolation of a gene
      specifically associated with the induction of mammary epithelial invasiveness at
      puberty.

PMID- 9287120
TI  - HIV-1 envelope protein, gp120, has no effects on inositol phosphate production
      and metabolism in the Jurkat T-cell line either in the presence or absence of
      receptor stimulation.
AB  - We have used HPLC techniques to investigate the effects of gp120 upon inositol
      phosphate turnover in Jurkat E6-1 CD4+ T-cells, to pursue previous reports that
      this viral coat protein: (a) inhibits receptor-activated inositol phosphate
      release; (b) stimulates basal inositol phosphate release; (c) inhibits inositol
      polyphosphate 5-phosphatase. Treatment of cells with up to 10 microg/ml gp120
      from between 10 min and 24 h was without effect upon inositol phosphate turnover
      in both basal cells, and in C305 and OKT3 stimulated cells. This is the first
      report that biologically competent gp120 does not affect any aspect of inositol
      phosphate turnover in either basal or receptor-activated lymphocytes.

PMID- 9287121
TI  - Glutamine accelerates interleukin-6 production by rat peritoneal macrophages in
      culture.
AB  - The effect of glutamine on the production of interleukin-6 (IL-6) was studied in
      rat peritoneal macrophages in culture. A maximal production of IL-6 was measured
      at 4 h in lipopolysaccharide (LPS)-stimulated macrophages, and addition of
      glutamine (5 mM) anticipated this increase by 1 h without any increase in the IL
      6 mRNA level. The effect of glutamine required the presence of LPS. Thus,
      glutamine accelerates IL-6 production from the pre-existing mRNA. The effect of
      glutamine was not mediated by cell swelling since culture of macrophages in
      hypoosmotic condition decreased the production of IL-6 in the culture medium with
      a corresponding decrease in the IL-6 mRNA level.

PMID- 9287122
TI  - Isolation and partial characterization of a novel and uncommon two-chain 64-kDa
      ribosome-inactivating protein from the bark of elder (Sambucus nigra L.).
AB  - A novel, strongly basic, two-chain ribosome-inactivating protein (RIP) with an
      apparent Mr of 64000 by SDS-PAGE and 63469 by mass spectrometry analysis, that we
      have named basic nigrin b, has been found in the bark of elder (Sambucus nigra
      L.). The new protein does not agglutinate red blood cells, even at high
      concentrations and displays an unusually and extremely high activity towards
      animal ribosomes (IC50 of 18 pg/ml for translation by rabbit reticulocyte
      lysates). However, it is inactive against plant and HeLa cells protein synthesis.
      Our functional and structural data are consistent with a heterodimeric structure
      for basic nigrin b of the type A-B*, B* being a truncated lectin lacking
      functional binding domains equivalent to the B (lectin) chain of the type 2 RIP
      SNA I and nigrin b present also in elder bark.

PMID- 9287123
TI  - Essential role of the first intron in the transcription of hsp90beta gene.
AB  - The human HSP90 gene family contains introns. There are two typical heat shock
      elements (HSE) in the first intron of human hsp90beta gene. As detected by
      chloramphenicol acetyl transferase (CAT) reporter activity assays, the HSE
      containing intron is essential in maintaining high constitutive expression and is
      critical for heat shock inducibility of the human hsp90beta gene. Cellular heat
      shock factor 1 (HSF 1) shows much higher binding affinity toward the intronic
      HSEs in comparison to an atypical HSE in the 5' flanking sequence. Novel
      initiation sites found in the first intron probably also contribute to
      constitutive and heat-inducible expression of the hsp90beta gene in Jurkat cells.

PMID- 9287124
TI  - Inhibitors of poly(ADP-ribose) polymerase suppress nuclear fragmentation and
      apoptotic-body formation during apoptosis in HL-60 cells.
AB  - The effects of 3-aminobenzamide (3ABm) and benzamide (BAm), known specific
      inhibitors of poly(ADP-ribose) polymerase (PARP), on actinomycin D (Act D)
      induced apoptosis in HL-60 cells were examined. These inhibitors had no
      appreciable effect on apoptotic DNA fragmentation, chromatin condensation or PARP
      restriction cleavage, but clearly inhibited morphological changes, especially
      nuclear fragmentation and apoptotic-body formation, in a dose-dependent manner.
      These results suggest that the synthesis of ADP-ribose polymers is not essential
      for the progression of apoptotic DNA fragmentation and chromatin condensation,
      but is required in the processes leading to nuclear fragmentation and the
      subsequent apoptotic-body formation during apoptosis in HL-60 cells.

PMID- 9287125
TI  - Cloning and characterization of a Drosophila adenylyl cyclase homologous to
      mammalian type IX.
AB  - A novel Drosophila adenylyl cyclase (AC) was identified by PCR using degenerate
      primers specific for the known metazoan ACs. The full-length cDNA predicts a
      protein displaying significant sequence homology with mammalian Type IX AC (AC9).
      The abundance and size of the message for the Drosophila AC9 homolog (DAC9)
      changes through development. Biochemical analysis of DAC9 confirms it encodes a
      functional enzyme which can be activated by forskolin or G protein. Together with
      the Drosophila Type I AC homolog encoded by the learning and memory gene,
      rutabaga, the molecular identification of DAC9 demonstrates there is a family of
      Drosophila AC isoforms reflecting at least part of the diversity of mammalian AC
      isoforms.

PMID- 9287126
TI  - In vitro membrane integration of leader peptidase depends on the Sec machinery
      and anionic phospholipids and can occur post-translationally.
AB  - A cell-free system based on a lysate and membrane vesicles from Escherichia coli
      is used to study characteristics of the membrane integration reaction of the
      polytopic membrane protein leader peptidase (Lep). Integration into inverted
      inner membrane vesicles was detected by partial protection against externally
      added protease. Integration is most efficient when coupled to translation but can
      also occur post-translationally and depends on the action of the proteinaceous
      Sec machinery and availability of anionic phospholipids. Lep is the first example
      of a membrane protein without cleavable signal sequence which requires anionic
      lipids for integration in vitro.

PMID- 9287127
TI  - Distinct type-2A protein phosphatases activate HMGCoA reductase and acetyl-CoA
      carboxylase in liver.
AB  - Acetyl-CoA carboxylase and HMGCoA reductase are inactivated by the same AMP
      activated protein kinase and are activated by type-2A protein phosphatase. To
      determine whether the same species of protein phosphatase-2A were involved, we
      studied the interconversion of acetyl-CoA carboxylase and HMGCoA reductase in
      isolated rat hepatocytes. We show that (i) these enzymes are differently
      regulated in hepatocytes and (ii) the species of type-2A protein phosphatase
      involved in their activation are different and can be separated by anion-exchange
      chromatography.

PMID- 9287128
TI  - Role of the prohormone convertase PC2 in the processing of proglucagon to
      glucagon.
AB  - Proglucagon is alternatively processed to glucagon in pancreatic alpha-cells, or
      to glucagon-like peptide-1 in intestinal L cells. Here, the specificity of PC2,
      the major prohormone convertase of alpha-cells, was examined both in vivo and in
      vitro. Adenovirus-mediated co-expression of proglucagon and PC2 in GH4C1 cells
      resulted in a pattern of processing products very similar to that observed in
      alpha-cells. Oxyntomodulin, an intermediate in the processing of proglucagon, was
      quantitatively converted to glucagon in vitro by purified recombinant PC2, in
      combination with carboxypeptidase E. It is concluded that PC2 is able to act
      alone in the pancreatic pathway of proglucagon processing.

PMID- 9287129
TI  - Requirement of nitric oxide and calcium mobilization for the induction of
      apoptosis in adrenal vascular endothelial cells.
AB  - Exposure of adrenal vascular endothelial cells (AVEC) to pharmacological nitric
      oxide (NO) donors, proinflammatory cytokines or lipopolysaccharide was unable to
      induce apoptosis as occurred when macrophages were treated under identical
      experimental conditions. However, when the intracellular Ca2+ concentration
      increased, AVEC displayed apoptotic features upon exposure to NO. This apoptosis
      was confirmed by the release of oligonucleosomes to the cytosol and by the
      characteristic DNA laddering observed after electrophoresis in agarose gels. Ca2+
      mobilizing agents and interleukin-1beta (IL-1beta) also elicited an apoptotic
      response in these cells through a mechanism that required NO synthesis. The
      ability of NO and intracellular Ca2+ to promote apoptosis was dependent on the
      number of passages of the cells in culture, suggesting the loss of protective
      factors in the course of ex vivo cell culture. Because AVEC exhibit an important
      capacity to increase the intracellular Ca2+ concentration in response to a wide
      array of agonists, this condition might affect the integrity of the vascular
      system under pathological circumstances such as those prevailing in the course of
      septic shock.

PMID- 9287130
TI  - Primary structure of matrilin-3, a new member of a family of extracellular matrix
      proteins related to cartilage matrix protein (matrilin-1) and von Willebrand
      factor.
AB  - A mouse cDNA encoding for matrilin-3, the third member of the novel matrilin
      family of extracellular matrix proteins, was cloned. The protein precursor of 481
      amino acids consists of a putative signal peptide, a short positively charged
      sequence, a single vWFA-like domain followed by four epidermal growth factor-like
      modules and a potential coiled-coil alpha-helical oligomerization domain at the C
      terminus. It is the smallest member of the matrilin family with a predicted Mr of
      the mature protein of 48 902. The primary structure of a C-terminal portion of
      310 amino acids of the human matrilin-3 was determined and showed a sequence
      identity to the mouse matrilin-3 of 84.8%. Northern blot hybridization of mouse
      matrilin-3 mRNA showed a 2.9 kb mRNA expressed in sternum, femur and trachea and
      indicates a cartilage-specific expression.

PMID- 9287131
TI  - Mutational analysis of human prothymosin alpha reveals a bipartite nuclear
      localization signal.
AB  - Mutants of human prothymosin alpha with impaired ability to inhibit yeast
      Saccharomyces cerevisiae. cerevisiae cell growth were characterized. Two types of
      prothymosin alpha-inactivating mutations were observed. Mutations that belong to
      the first type compromised the nuclear entry of prothymosin alpha by affecting
      its nuclear localization signal. Analysis of subcellular distribution of GFP
      prothymosin alpha fusions revealed a bipartite nuclear localization signal that
      is both necessary and sufficient for nuclear import of the protein in human
      cells. Mutations of the second type abrogated the inhibitory action of
      prothymosin alpha through an unknown mechanism, without influencing the nuclear
      import of the protein.

PMID- 9287132
TI  - Amino acid substitutions in the first transmembrane domain (TM1) of P
      glycoprotein that alter substrate specificity.
AB  - Recently, we showed that the amino acid at position 61 in TM1 of human P
      glycoprotein is important in deciding the substrate specificity of this protein.
      In this work, we investigated whether the amino acids other than His61 in TM1 of
      P-glycoprotein are also essential in the function of this protein. Nine amino
      acids residues, from Ala57 to Leu65 in TM1, were independently substituted to
      Arg, and analyzed the drug resistance of cells stably expressing each of these
      mutant P-glycoproteins. The mutant P-glycoproteins Ile60 --> Arg, His61 --> Arg,
      Ala63 --> Arg, Gly64 --> Arg, and Leu65 --> Arg were normally processed and
      expressed in the plasma membrane. Substrate specificities of mutant P
      glycoproteins Gly64 --> Arg and Leu65 --> Arg were quite different from that of
      the wild type, and similar to that of the His61 --> Arg mutant, while the Ile60 -
      > Arg and Ala63 --> Arg mutant P-glycoproteins showed similar substrate
      specificities to that of the wild-type P-glycoprotein, suggesting that not only
      the amino acid residue at position 61 but also those at position 64 and 65 are
      also important in deciding the substrate specificity of P-glycoprotein. These
      three amino acids His61, Gly64, and Leu65 would form a compact region on an alpha
      helix arrangement of TM1. These results suggest that a region consisting of
      His61, Gly64, and Leu65 in TM1 would participate in the formation of the
      recognition site for substrates of P-glycoprotein.

PMID- 9287133
TI  - Apoptosis induction by inhibitors of Ser/Thr phosphatases 1 and 2A is associated
      with transglutaminase activation in two different human epithelial tumour lines.
AB  - Two epithelial tumour lines, HeLa and KB, were treated with okadaic acid and
      calyculin A, specific inhibitors of Ser/Thr phosphatases (PP), esp. PP1 and PP2A.
      Morphological criteria, analysis of DNA fragmentation and studies of membrane
      integrity revealed that both agents concentration- and time-dependently induced
      apoptosis at nanomolar concentrations which in these cells was associated with
      the stimulation of a transglutaminase activity. Since a non-functional derivative
      of okadaic acid did not affect cell viability apoptosis was apparently related to
      the inhibition of PP1 and PP2A. Membrane damage marker activity was delayed by at
      least 24 h when compared to nuclear alterations.

PMID- 9287134
TI  - The protein kinase C pseudosubstrate peptide (PKC19-36) inhibits insulin
      stimulated protein kinase activity and insulin-mediated translocation of the
      glucose transporter glut 4 in streptolysin-O permeabilized adipocytes.
AB  - The effect of insulin on protein kinase activity and plasma membrane
      translocation of the glucose transporter GLUT 4 has been studied in adipocytes
      permeabilized by Streptolysin-O. Insulin increased protein kinase activity, and
      this was completely inhibited by the PKC pseudosubstrate inhibitor peptide (PKC19
      36). Insulin-mediated translocation of GLUT 4 was also inhibited by the PKC
      inhibitor peptide. Both these insulin effects were blocked by a PKCbeta
      neutralizing antibody. Our results are consistent with the hypothesis that
      insulin activates PKCbeta activity in adipocytes in situ, and that this PKC
      activation is a component of the system whereby insulin regulates translocation
      of GLUT 4 to the plasma membrane.

PMID- 9287135
TI  - Role of dopamine at the onset of pupal diapause in the cabbage armyworm Mamestra
      brassicae.
AB  - Experiments were conducted to examine the relationship between an onset of
      diapause and dopamine (DA) content in the cabbage armyworm Mamestra brassicae
      during pupation. The DA levels were significantly higher in haemolymph,
      integument and brain-central nervous system of diapause-destined pupae than in
      non-diapause-destined pupae. The elevated level of the integumental DA content
      was demonstrated to be due to an increase in dopa decarboxylase activity in
      diapausing pupal integuments through an enhancement of transcript levels of this
      enzyme. Elevation of the DA level accomplished by feeding L-DOPA to last instar
      larvae induced a diapause-like state in more than 50% of the pupae under long
      daylengths.

PMID- 9287136
TI  - Two regions in c-myb proto-oncogene product negatively regulating its DNA-binding
      activity.
AB  - The c-myb proto-oncogene product (c-Myb) is a transcriptional regulator that
      binds to the specific DNA sequence. Deletion of the negative regulatory domain
      (NRD) in the carboxyl-proximal region of c-Myb results in both increased trans
      activating capacity and oncogenic activation. One possible mechanism to modulate
      c-Myb activity is a regulation of DNA-binding activity. However, it is not known
      whether any region in NRD affects the in vivo DNA-binding activity of c-Myb.
      Using the highly transfectable cell line 293T, we developed a system to precisely
      measure the DNA-binding activity of Myb expressed in mammalian cells. Using this
      system, two regions in NRD were shown to repress DNA-binding activity. These
      results suggest that DNA-binding activity of c-Myb is independently regulated by
      multiple mechanisms through these subdomains.

PMID- 9287138
TI  - Purification, characterization and cloning of a novel variant of the superantigen
      Yersinia pseudotuberculosis-derived mitogen.
AB  - The novel superantigen designated as Yersinia pseudotuberculosis-derived mitogen
      typeB (YPMb) was purified from the cell lysate of Y. pseudotuberculosis O:6
      strain (R-104). Proliferative response of human peripheral blood mononuclear
      cells to the purified YPMb was detectable at a concentration of as low as 1
      pg/ml, that is comparable to the previously documented YPM (YPMa). The Vbeta
      repertoire specificity (3, 9, 13.1 and 13.2) of YPMb was also the same as that of
      YPMa. A gene (ypmB) encoding YPMb was cloned and its nucleotide sequence was
      determined. The open reading frame (ORF 453 bp) of the ypmB encodes a protein
      with 150 amino acid residues, though the precursor protein of YPMa consists of
      151 amino acid residues. There is a nucleotide sequence homology of 88.9% between
      ypmB and ypmA. The low homology in the downstream of the structural gene between
      ypmB and ypmA and the difference in the GC content in the ORF of ypmB and ypmA
      from that of the base usage of Y. pseudotuberculosis suggest that the ypm gene
      originates from another organism. The alignment of the amino acid sequences of
      mature proteins of YPMb and YPMa revealed that there is 83% homology (108 amino
      acid residues are identical). Between YPMa and YPMb, the central region is less
      homologous than the N- and C-terminal regions. Based on the functional similarity
      of two superantigen molecules, the less homology suggested that the central
      region is less important for the function of both YPM molecules.

PMID- 9287137
TI  - Site-directed mutagenesis of maize recombinant C4-pyruvate,orthophosphate
      dikinase at the phosphorylatable target threonine residue.
AB  - A key regulatory enzyme of the C4-photosynthetic pathway is stromal
      pyruvate,orthophosphate dikinase (PPDK, EC 2.7.9.1). As a pivotal enzyme in the
      C4 pathway, it undergoes diurnal light-dark regulation of activity which is
      mediated by a single bifunctional regulatory protein (RP). RP specifically
      inactivates PPDK in the dark by an ADP-dependent phosphorylation of an active
      site Thr residue (Thr-456 in maize). Conversely, RP activates inactive PPDK in
      the light by phosphorolytic dephosphorylation of this target Thr-P residue. We
      have employed a His-tagged maize recombinant C4 PPDK for directed mutagenesis of
      this active-site regulatory Thr. Three such mutants (T456V, T456S, T456D) were
      analyzed with respect to overall catalysis and regulation by exogenous maize RP.
      Substitution with Val and Ser at this position does not affect overall catalysis,
      whereas Asp abolishes enzyme activity. With respect to regulation by RP, it was
      found that Ser can effectively substitute for the wild-type Thr residue in that
      mutant enzyme is phosphorylated and inactivated by RP. The T456V mutant, however,
      could not be phosphorylated and was, thus, resistant to ADP-dependent
      inactivation by RP.

PMID- 9287139
TI  - Immunoliposomes bearing polyethyleneglycol-coupled Fab' fragment show prolonged
      circulation time and high extravasation into targeted solid tumors in vivo.
AB  - We have developed a new type of long-circulating immunoliposome (Fab'-PEG
      immunoliposomes) which is efficiently extravasated into the targeted solid tumor
      in vivo. Small unilamellar liposomes (100-130 nm in diameter) were prepared from
      distearoylphosphatidylcholine (DSPC), cholesterol (CHOL) and a
      dipalmitoylphosphatidylethanolamine derivative of PEG with a terminal maleimidyl
      group (DPPE-PEG-Mal), and conjugated Fab' fragment of antibody. Inclusion of DPPE
      PEG-Mal and linkage of the Fab' fragment instead of intact antibody to PEG
      terminals allowed the liposomes to evade RES uptake and remain in the circulation
      for a long time, resulting in enhanced accumulation of the liposomes in the solid
      tumor. Because of the ability of such Fab'-PEG immunoliposomes to target solid
      tumors, they appear highly attractive as carriers of not only chemotherapeutic
      agents, but also of macromolecular drugs.

PMID- 9287141
TI  - Annexin I targets S100C to early endosomes.
AB  - Immunofluorescence and subcellular fractionation localize annexin I and the EF
      hand protein S100C to the same membranous structures which in part correspond to
      transferrin receptor-positive endosomes. The association of S100C with endosomal
      membranes is strictly dependent on annexin I binding since a D91stop-S100C mutant
      protein, in which the residues essential for annexin I binding have been removed,
      fails to colocalize with membraneous structures. This indicates that annexin I
      and S100C form a complex in vivo and that the endosomal localization of this
      complex is mediated through an interaction of annexin I with the endosomal
      membrane.

PMID- 9287140
TI  - Isolation and characterization of replication protein A (RP-A) from tobacco
      cells.
AB  - Replication protein A (RP-A) was isolated from tobacco suspension cells and
      purified to near homogeneity by a procedure involving isolation of protoplasts,
      preparation of nuclei, nuclear lysis, binding to a column of single-stranded (ss)
      DNA cellulose and elution at different salt concentrations. The purified protein
      contained three subunits with molecular masses of 70, 34 and 14 kDa, and was free
      from nuclease activity. Tobacco RP-A had a high affinity for ssDNA. Binding
      competition experiments indicated only a weak affinity for double-stranded DNA
      and no detectable affinity for ssRNA. Photochemical cross-linking experiments
      indicated that the 70 kDa subunit has the ssDNA-binding activity. Tobacco RP-A
      was able to stimulate the activity of a tobacco alpha-like DNA polymerase about 4
      fold. This is the first isolation of RP-A from a plant and the procedure may be
      generally applicable to other plant species.

PMID- 9287142
TI  - LacZ and interleukin-3 expression in vivo after retroviral transduction of marrow
      derived human osteogenic mesenchymal progenitors.
AB  - Human marrow-derived mesenchymal progenitor cells (hMPCs), which have the
      capacity for osteogenic and marrow stromal differentiation, were transduced with
      the myeloproliferative sarcoma virus (MPSV)-based retrovirus, vM5LacZ, that
      contains the LacZ and neo genes. Stable transduction and gene expression occurred
      in 18% of cells. After culture expansion and selection in G418, approximately 70%
      of neo(r) hMPCs co-expressed LacZ. G418-selected hMPC retain their osteogenic
      potential and form bone in vivo when seeded into porous calcium phosphate ceramic
      cubes implanted subcutaneously into SCID mice. LacZ expression was evident within
      osteoblasts and osteocytes in bone developing within the ceramics 6 and 9 weeks
      after implantation. Likewise, hMPCs transduced with human interleukin-3 (hIL-3)
      cDNA, adhered to ceramic cubes and implanted into SCID mice, formed bone and
      secreted detectable levels of hIL-3 into the systemic circulation for at least 12
      weeks. These data indicate that genetically transduced, culture-expanded bone
      marrow-derived hMPCs retain a precursor phenotype and maintain similar levels of
      transgene expression during osteogenic lineage commitment and differentiation in
      vivo. Because MPCs have been shown to differentiate into bone, cartilage, and
      tendon, these cells may be a useful target for gene therapy.

PMID- 9287143
TI  - Replicative potential and telomere length in human skeletal muscle: implications
      for satellite cell-mediated gene therapy.
AB  - In this study, we have evaluated the ability of human satellite cells isolated
      from subjects aged from 5 days to 86 years to proliferate in culture. Cells were
      cultivated until they became senescent. The number of cell divisions was
      calculated by counting the number of cells plated in culture compared to the
      number of cells removed following proliferation. Telomere length, which is known
      to decrease during each round of cell division, has been used to analyze the in
      vitro replicative capacity and in vivo replicative history of human satellite
      cells at isolation. The rate of telomere shortening in myonuclei of these muscle
      biopsies was also examined. Our results show that both proliferative capacity and
      telomere length of satellite cells decreases with age during the first two
      decades but that the myonuclei of human skeletal muscle are remarkably stable
      because telomere length in these myonuclei remains constant from birth to 86
      years. The lack of shortening of mean terminal restriction fragments (TRF) in
      vivo confirms that skeletal muscle is a stable tissue with little nuclear
      turnover and therefore an ideal target for cell-mediated gene therapy. Moreover,
      our results show that it is important to consider donor age as a limiting factor
      to obtain an optimal number of cells.

PMID- 9287144
TI  - Induction of a cAMP-stimulated chloride secretion in regenerating poorly
      differentiated airway epithelial cells by adenovirus-mediated CFTR gene transfer.
AB  - In cystic fibrosis (CF), the airway epithelium is in the process of injury and
      regeneration. In the context of the CF gene therapy, we previously reported that
      regenerating poorly differentiated (PD) cells of human airway epithelium
      represent preferential cell targets for recombinant adenoviral gene vectors. To
      define whether PD non-CF and CF epithelial cells possess a functional cystic
      fibrosis transmembrane conductance regulator protein (CFTR) chloride channel, we
      analyzed the CFTR expression and the regulation of chloride secretion under
      cyclic (c)AMP stimulation in these regenerating PD epithelial cells of non-CF and
      CF airway tissue. Moreover, we studied the effects of CFTR gene transfer mediated
      by a replication-defective adenovirus containing the wild-type CFTR gene (AdCFTR)
      on CFTR expression and on cAMP-stimulated chloride secretion. Distribution of the
      CFTR protein was evaluated in regenerating PD airway cells by light fluorescence
      microscopy and scanning laser confocal microscopy. The cAMP-mediated regulation
      of cell membrane chloride secretion was investigated using the whole-cell patch
      clamp and SPQ (6-methoxy-N-[3-sulfopropyl]quinolinium) techniques. Compared with
      the absence of CFTR expression and cAMP-regulated chloride secretion in
      nontransduced regenerating PD cells of either non-CF or CF origin, transduction
      with AdCFTR induces a CFTR expression and a cAMP-regulated stimulation of the
      cell membrane chloride secretion in the regenerating PD cells. These results
      suggest that, out of the context of CF, remodeled and poorly differentiated
      airway epithelium may present abnormalities in ion transport. Moreover, our data
      suggest that, in the context of CF gene therapy, adenoviral vectors can be
      efficient in correcting, at least partially, the chloride secretion defect in the
      remodeled CF airway epithelium.

PMID- 9287145
TI  - CTL response and protection against P815 tumor challenge in mice immunized with
      DNA expressing the tumor-specific antigen P815A.
AB  - A DNA immunization approach was used to induce an immune response against the
      tumor-specific antigen P815A in DBA/2 mice. The P1A gene, which encodes the P815A
      antigen, was modified by the addition of a short sequence coding for a tag
      epitope recognized by the monoclonal antibody AU1, and cloned into the eukaryotic
      expression vector pBKCMV, resulting in plasmid pBKCMV-P1A. L1210 cells stably
      transfected with pBKCMV-P1A expressed P1A mRNA and were lysed by the syngeneic
      P815A-specific cytotoxic clone CTL-P1:5, thus confirming that the tag-modified
      P1A protein underwent correct processing and presentation. A single intramuscular
      injection of 100 microg of pBKCMV-P1A induced the expression of P1A mRNA for at
      least 4 months. Eighty percent of DBA/2 mice injected three times with 100 microg
      of pBKCMV-P1A generated cytotoxic T lymphocytes (CTL) that lysed P815 tumor
      cells, whereas mock-inoculated animals failed to show any cytotoxicity. Moreover,
      experiments designed to evaluate the protection of pBKCMV-P1A-immunized mice
      against a lethal challenge with P815 tumor cells showed that 6 of 10 immunized
      mice rejected the tumor, and 2 mice showed prolonged survival compared to control
      animals.

PMID- 9287146
TI  - Retroviral particles produced from a stable human-derived packaging cell line
      transduce target cells with very high efficiencies.
AB  - The goal of this work was to determine whether a stable 293 amphotropic packaging
      line, which we have designated 293-SPA, is useful for the production of high
      titer stable virus by comparison to the murine psiCRIP line. Here, we report our
      unexpected findings that particles derived from the 293-SPA line transduce target
      cells (both NIH-3T3 cells and primary melanoma cells) with greatly enhanced
      efficiencies (at least 10-fold) compared to particles derived from the psiCRIP
      packaging line. We show that the presence of a transferable inhibitor in the
      psiCRIP line at least partially accounts for this dramatic difference in
      transduction efficiency. This work has important implications for improving the
      efficiency of retrovirus-mediated gene transfer in general as well as in the
      design of new packaging cell lines.

PMID- 9287147
TI  - Myositis induced by naked DNA immunization with the gene for histidyl-tRNA
      synthetase.
AB  - Polymyositis is regarded as an autoimmune inflammatory muscle disease. A major
      subgroup of patients have autoantibodies to cellular histidyl-transfer RNA
      synthetase (HRS). We have analyzed the role of the autoantigen HRS in the
      induction of murine myositis in a comparative study of inoculation of BALB/c mice
      with recombinant HRS protein versus naked DNA coding for HRS. Adult BALB/c mice
      produced antibodies to human HRS following inoculation with HRS protein and
      adjuvant, but myositis was not observed. Alternatively, expression plasmid DNA
      constructs encoding full-length and truncated human HRS were inoculated
      intramuscularly in gene transfer studies. DNA-inoculated mice produced relatively
      low anti-HRS antibody titers. However, in contrast to recombinant HRS protein
      inoculated mice, HRS gene transfer induced pathology with evidence of cellular
      infiltration of perivascular and endomysial regions of the inoculated muscle.
      Multiple inoculations of a plasmid construct encoding a hybrid molecule
      consisting of HRS and the transferrin receptor cytoplasmic tail induced the
      highest levels of antibodies and persisting cellular infiltration. Unlike HRS,
      expression of influenza virus hemagglutinin (HA) following inoculation of an HA
      plasmid did not induce myositis. Transfer of naked DNA constructs expressing HRS
      is likely to provide valuable information on the autoimmune response to this
      protein and its role in the development of myositis.

PMID- 9287148
TI  - Gut epithelial cells as targets for gene therapy of hemophilia.
AB  - Gut epithelium is an attractive target for gene therapy of hemophilia due to the
      large number of rapidly dividing cells that should be readily accessible to a
      wide range of vectors by a noninvasive route of administration. We have performed
      in vitro tests to determine the suitability of gut epithelial cells for gene
      transfer, protein synthesis, and secretion of coagulation factors VIII and IX.
      The results with retroviral vectors indicate that transduced epithelial cells
      from human, rat, or porcine small or large intestine can synthesize significant
      amounts of factor VIII or factor IX and that two-thirds or more of the
      recombinant protein is secreted in a basolateral direction (i.e., away from the
      lumen and toward underlying capillaries and lymphatics). Furthermore, we have
      demonstrated that intestinal epithelial cells are susceptible to efficient gene
      transfer by lipofection and adenovirus vectors. In the case of factor IX, we have
      produced a high-titer adenovirus vector capable of transducing gut epithelial
      cells resulting in synthesis of factor IX. The results of our in vitro studies
      indicate that gene transfer targeting gut epithelium as a new approach to
      hemophilia gene therapy is rational and merits in vivo studies in hemophilia
      animal models.

PMID- 9287149
TI  - Highly efficient retrovirus-mediated gene transfer into rat hepatocytes in vivo.
AB  - We have used high-titer (10(8) ffu/ml) recombinant retroviral vectors to transfer
      the beta-galactosidase (beta-Gal) gene to rat hepatocytes in vivo. In animals
      injected twice in the portal blood stream the next day after partial hepatectomy,
      half of the hepatocytes (46 +/- 17%) expressed the marker at the end of liver
      regeneration. The number of positive cells closely correlated with the viral
      titer as well as with beta-Gal enzymatic activity present in the whole liver.
      Because genes transferred via retroviral vectors in the liver are known to be
      expressed permanently, our present results open new possibilities for the
      development of gene therapy protocols for hereditary liver diseases using
      recombinant retroviral vectors.

PMID- 9287150
TI  - Aminoacyl thioester chemistry of class II aminoacyl-tRNA synthetases.
AB  - Lysyl-tRNA synthetase, a class II enzyme, edits homocysteine by converting it
      into homocysteine thiolactone. In a similar reaction, the enzyme converts
      homoserine into homoserine lactone. Other class II enzymes, aspartyl-tRNA
      synthetase and seryl-tRNA synthetase, do not edit any of the amino acids tested.
      However, all three class II aminoacyl-tRNA synthetases catalyze AMP- and
      pyrophosphate-independent deacylation of cognate aminoacyl-tRNA in the presence
      of thiols, mimicking editing of homocysteine. Thiol-dependent deacylations
      exhibit saturation kinetics with respect to concentration of thiols, suggesting
      the presence of a thiol binding site on each enzyme. 3-Mercaptopropionate-, N
      acetyl-L-cysteine-, and dithiothreitol-dependent deacylations of aminoacyl-tRNA
      yield corresponding aminoacyl thioesters. Cysteine-dependent enzymatic
      deacylations of aminoacyl-tRNA by these class II enzymes yield dipeptides, N
      (aminoacyl)cysteine. The formation of N-(aminoacyl)cysteine involves thioester
      intermediates S-(aminoacyl)-L-cysteine, which are not observed because of the
      facile transacylation of the aminoacyl residue from the sulfur to the alpha-amino
      group of cysteine to form a stable peptide bond. These data indicate that class
      II aminoacyl-tRNA synthetases possess unique thiol-binding subsites within their
      active sites. That the thiol-binding subsite exists also in AspRS and SerRS,
      which do not need editing function, suggests that these class II enzymes possess
      vestigial editing functions.

PMID- 9287151
TI  - Site-directed mutagenesis of putative active site residues of MunI restriction
      endonuclease: replacement of catalytically essential carboxylate residues
      triggers DNA binding specificity.
AB  - Mapping of the conserved sequence regions in the restriction endonucleases MunI
      (C/AATTG) and EcoRI (G/AATTC) to the known X-ray structure of EcoRI allowed us to
      identify the sequence motif 82PDX14EXK as the putative catalytic/Mg2+ ion binding
      site of MunI [Siksnys, V., Zareckaja, N., Vaisvila, R., Timinskas, A., Stakenas,
      P., Butkus, V., & Janulaitis, A. Gene (1994) 142, 1-8]. Site-directed mutagenesis
      was then used to test whether amino acids P82, D83, E98, and K100 were important
      for the catalytic activity of MunI. Mutation P82A generated only a marginal
      effect on the cleavage properties of the enzyme. Investigation of the cleavage
      properties of the D83, E98, and K100 substitution mutants, however, in vivo and
      in vitro, revealed either an absence of catalytic activity or markedly reduced
      catalytic activity. Interestingly, the deleterious effect of the E98Q replacement
      in vitro was partially overcome by replacement of the metal cofactor used. Though
      the catalytic activity of the E98Q mutant was only 0.4% of WT under standard
      conditions (in the presence of Mg2+ ions), the mutant exhibited 40% of WT
      catalytic activity in buffer supplemented with Mn2+ ions. Further, the DNA
      binding properties of these substitution mutants were analyzed using the gel
      shift assay technique. In the absence of Mg2+ ions, WT MunI bound both cognate
      DNA and noncognate sequences with similar low affinities. The D83A and E98A
      mutants, in contrast, in the absence of Mg2+ ions, exhibited significant
      specificity of binding to cognate DNA, suggesting that the substitutions made can
      simulate the effect of the Mg2+ ion in conferring specificity to the MunI
      restriction enzyme.

PMID- 9287152
TI  - DNA binding specificity of MunI restriction endonuclease is controlled by pH and
      calcium ions: involvement of active site carboxylate residues.
AB  - Gel shift analysis reveals [Lagunavicius, A., & Siksnys, V. (1997) Biochemistry
      36 (preceding paper in this issue)] that at pH 8.3 in the absence of Mg2+, MunI
      restriction endonuclease exhibits little DNA binding specificity, as compared
      with the D83A and E98A mutants of MunI. This suggests that charged carboxylate
      residue(s) influence the DNA binding specificity of MunI. In our efforts to
      establish the determinants of MunI binding specificity, we investigated the
      possible role of the ionic milieu, and we found that lowering pH or elevating
      Ca2+ levels per se induces specific DNA recognition by WT MunI. In contrast to
      the binding experiments at pH 8.3, gel shift analysis at pH 6.5 indicated tight
      sequence-specific binding of WT MunI in the absence of Mg2+, suggesting that
      protonation of active site carboxylate residue(s) which manifest anomalously high
      pKa value(s) control binding specificity. Interestingly, Ca2+ ion concentrations,
      which did not support DNA cleavage by MunI also induced DNA binding specificity
      in WT MunI at pH 8.3. To explore possible structural changes upon DNA binding, we
      then used a limited proteolysis technique. Trypsin cleavage of MunI-DNA complexes
      indicated that in the presence of cognate DNA the MunI restriction endonuclease
      became resistant to proteolytic cleavage, suggesting that binding of specific DNA
      induced a structural change. CD measurements confirmed this observation,
      suggesting minor secondary structural differences between complexes of MunI with
      cognate and noncognate DNA. These results therefore suggest that binding of MunI
      to its recognition sequence triggers a conformational transition that correctly
      juxtaposes active site carboxylate residues, which then chelate Mg2+ ions. In the
      absence of Mg2+ ions, at pH 8.3, conditions in which carboxylate groups would be
      expected to be completely ionized, electrostatic repulsion between charged
      carboxylates and phosphate oxygens is enhanced such as to interfere with specific
      DNA binding. Elimination of such repulsive constraints by replacement of
      carboxylate residues, by lowering pH, or by metal ion binding, then promotes MunI
      binding specificity.

PMID- 9287153
TI  - Structure-function relationships in Anabaena ferredoxin: correlations between X
      ray crystal structures, reduction potentials, and rate constants of electron
      transfer to ferredoxin:NADP+ reductase for site-specific ferredoxin mutants.
AB  - A combination of structural, thermodynamic, and transient kinetic data on wild
      type and mutant Anabaena vegetative cell ferredoxins has been used to investigate
      the nature of the protein-protein interactions leading to electron transfer from
      reduced ferredoxin to oxidized ferredoxin:NADP+ reductase (FNR). We have
      determined the reduction potentials of wild-type vegetative ferredoxin,
      heterocyst ferredoxin, and 12 site-specific mutants at seven surface residues of
      vegetative ferredoxin, as well as the one- and two-electron reduction potentials
      of FNR, both alone and in complexes with wild-type and three mutant ferredoxins.
      X-ray crystallographic structure determinations have been carried out for six of
      the ferredoxin mutants. None of the mutants showed significant structural changes
      in the immediate vicinity of the [2Fe-2S] cluster, despite large decreases in
      electron-transfer reactivity (for E94K and S47A) and sizable increases in
      reduction potential (80 mV for E94K and 47 mV for S47A). Furthermore, the
      relatively small changes in Calpha backbone atom positions which were observed in
      these mutants do not correlate with the kinetic and thermodynamic properties. In
      sharp contrast to the S47A mutant, S47T retains electron-transfer activity, and
      its reduction potential is 100 mV more negative than that of the S47A mutant,
      implicating the importance of the hydrogen bond which exists between the side
      chain hydroxyl group of S47 and the side chain carboxyl oxygen of E94. Other
      ferredoxin mutations that alter both reduction potential and electron-transfer
      reactivity are E94Q, F65A, and F65I, whereas D62K, D68K, Q70K, E94D, and F65Y
      have reduction potentials and electron-transfer reactivity that are similar to
      those of wild-type ferredoxin. In electrostatic complexes with recombinant FNR,
      three of the kinetically impaired ferredoxin mutants, as did wild-type
      ferredoxin, induced large (approximately 40 mV) positive shifts in the reduction
      potential of the flavoprotein, thereby making electron transfer thermodynamically
      feasible. On the basis of these observations, we conclude that nonconservative
      mutations of three critical residues (S47, F65, and E94) on the surface of
      ferredoxin have large parallel effects on both the reduction potential and the
      electron-transfer reactivity of the [2Fe-2S] cluster and that the reduction
      potential changes are not the principal factor governing electron-transfer
      reactivity. Rather, the kinetic properties are most likely controlled by the
      specific orientations of the proteins within the transient electron-transfer
      complex.

PMID- 9287155
TI  - Mutations induced by 2-hydroxyadenine on a shuttle vector during leading and
      lagging strand syntheses in mammalian cells.
AB  - An oxidatively damaged base, 2-hydroxyadenine (2-OH-Ade), was incorporated into a
      predetermined site of one of the strands {(+)- or (-)-strand} of the double
      stranded shuttle vector, pSVK3, and the modified DNAs were transfected into
      simian COS-7 cells. The nucleotide sequences in which the modified base was
      incorporated were 5'-GTCGA*C and 5'-CTTA*AG (A* represents 2-OH-Ade). The former
      is the recognition site for the restriction enzyme SalI, and the latter is that
      for AflII. The DNAs replicated in the cells were recovered and were transfected
      again into Escherichia coli. The DNAs recovered from the COS-7 cells transfected
      with a plasmid containing 2-OH-Ade at either site of the (+)-strand (a template
      strand for lagging strand synthesis) formed colonies about 50%-70% as frequently
      as the unmodified DNA. This indicated that the base weakly blocked DNA
      replication during lagging strand synthesis. On the other hand, the base in the (
      )-strand did not appear to affect the efficiency of leading strand synthesis in
      COS-7 cells. The mutation frequencies of 2-OH-Ade in COS-7 cells were 0.6%-0.1%,
      depending on the sequence and the strand location. Although the mutation spectra
      of 2-OH-Ade also differed with sequences and strands, the base elicited
      substitution and deletion mutations in mammalian cells, as in E. coli. These
      results indicate that 2-OH-Ade is mutagenic in eukaryotic cells as well as in
      prokaryotic cells.

PMID- 9287154
TI  - Specificity of DNA repair methyltransferases determined by competitive
      inactivation with oligonucleotide substrates: evidence that Escherichia coli Ada
      repairs O6-methylguanine and O4-methylthymine with similar efficiency.
AB  - DNA repair methyltransferases (MTases) are stoichiometric acceptor molecules that
      are irreversibly inactivated in the course of removing a methyl group from O6
      methylguanine (meG)-DNA or O4-methylthymine (meT)-DNA. A new assay has been
      developed to determine the relative efficiency of repair of meG and meT. The
      assay is based on the deprotection of methylated restriction sites in synthetic
      oligonucleotides and can be used to measure meG repair or meT repair directly.
      More importantly, relative repair efficiencies can be measured in competition
      experiments, using each of the methylated oligomers in turn as an inhibitor of
      repair for the other. Relative repair rates are determined by numerical solution
      of the coupled rate equations that describe this competition to the experimental
      data. We find that the human MTase repairs meT about 35-fold less well than meG,
      qualitatively similar to earlier studies. Contrary to previous reports, however,
      we find that Escherichia coli Ada repairs meG and meT with nearly equal
      efficiency. This finding, in conjunction with other recent reports, may indicate
      that low meT repair is a relatively unusual characteristic of the human homolog.

PMID- 9287156
TI  - Effects of Mg2+ and the 2' OH of guanosine on steps required for substrate
      binding and reactivity with the Tetrahymena ribozyme reveal several local folding
      transitions.
AB  - Transient kinetic studies with fluorescence detection were used to determine the
      effects of Mg2+ concentration and the 2' OH group of guanosine monophosphate,
      prG, substrate on various steps in the transesterification reaction of prG with
      5' pyrene-labeled oligonucleotides as catalyzed by the L-21 ScaI ribozyme. The
      effect of increasing Mg2+ from 5 to 10 mM on the rate constants of association
      and dissociation of 5' pyrene-labeled CUCUA at 15 degrees C was measured. The
      rate constant of association increases about 3-fold to (8.7 +/- 0.7) x 10(6) M-1
      s-1 at 10 mM Mg2+. The rate constant for dissociation is 25 +/- 4 s-1 at 10 mM
      Mg2+, within experimental error of the rate constant of 17 +/- 5 s-1 measured at
      5 mM Mg2+. This Mg2+ dependence is attributed to nonspecific binding of Mg2+ to
      the duplex helix. In the absence of prG, no docking of substrate is observed. The
      effect of Mg2+ concentration on rates for docking of 5' pyrene-labeled substrate,
      pyrCCUCUA, were measured at [Mg2+] >/= 2 mM and at temperatures </= 20 degrees C,
      where optical melting curves indicate global folding is complete. Thus the rates
      monitor local folding steps important for catalytic function. Three and possibly
      four local cooperative transitions were induced by Mg2+. The fastest fluorescence
      transient, which is associated with substrate docking, changes from a quenching
      to an enhancement between 2 and 4 mM Mg2+, and its observed rate constant at pH
      6.5 and 7.5 is about 1 s-1, independent of [Mg2+] when 4 </= [Mg2+] </= 15 mM.
      The slowest fluorescence transient, which is apparently associated with
      transesterification, has an observed rate constant that continues to increase
      when [Mg2+] >/= 4 mM. In the presence of Ca2+, such that [Ca2+] + [Mg2+] = 15 mM,
      the observed rate constants of both transients are constant when 4 mM </= [Mg2+]
      </= 7 mM but double between 7 and 11 mM Mg2+. At pH 6.5 when 4 mM </= [Mg2+] </=
      7 mM in the absence of Ca2+, there is also evidence for a third transient with a
      Mg2+-dependent observed rate constant that is intermediate between the observed
      rate constants of docking and transesterification. Thus these experiments reveal
      several separable, local folding transitions that are dependent on Mg2+ in a very
      cooperative manner and are important for function. When pdG is substituted for
      prG, no transesterification is observed, and fluorescence quenching is observed
      for 1-15 mM Mg2+. The switch from fluorescence enhancements with prG to quenching
      with pdG suggests the 2' OH of prG is important for proper positioning of
      substrate in the catalytic site.

PMID- 9287157
TI  - Cloning, overexpression, and biochemical characterization of the catalytic domain
      of MutY.
AB  - Proteolysis of MutY with trypsin indicated that this DNA mismatch repair enzyme
      could exist as two modules and that the N-terminal domain (Met1-Lys225),
      designated as p26, could serve as the catalytic domain [Manuel et al. (1996) J.
      Biol. Chem. 271, 16218-16226]. In this study, the p26 domain has been cloned,
      overproduced, and purified to homogeneity. Synthetic DNA duplexes containing
      mismatches, generated with regular bases and nucleotide analogs containing
      altered functional groups, have been used to characterize the substrate
      specificity and mismatch repair efficiency of p26. In general, p26 recognized and
      cleaved most of the substrates which were catalyzed by the intact protein.
      However, p26 displayed enhanced specificity for DNA containing an inosine.
      guanine mismatch, and the specificity constant (Kcat/Km) was 2-fold higher. The
      truncated MutY was able to cleave DNA containing an abasic site with equal
      efficiency. Dissociation constants (Kd) were obtained for p26 on noncleavable DNA
      substrates containing a tetrahydrofuran (abasic site analog) or a reduced abasic
      site. p26 bound these substrates with high specificity, and the Kd values were 3
      fold higher when compared to the intact MutY. p26 contains both DNA glycosylase
      and AP lyase activities, and we provide evidence for a reaction mechanism that
      proceeds through an imino intermediate. Thus, we have shown for the first time
      that deletion of 125 amino acids at the C-terminus of MutY generates a stable
      catalytic domain which retains the functional identity of the intact protein.

PMID- 9287158
TI  - Analysis of ion transport perturbations caused by hu MDR 1 protein
      overexpression.
AB  - In previous work [Luz et al. (1994) Biochemistry 33, 7239-7249; Roepe et al.
      (1994) Biochemistry 33, 11008-11015] we measured changes in Cl- and HCO3-
      dependent pHi regulation for LR73 Chinese hamster ovary fibroblasts
      overexpressing mu MDR 1 protein. However, only one clonal cell line
      overexpressing the protein but not previously exposed to chemotherapeutic drug
      (i.e., a "true" transfectant) was examined, since very few MDR cell lines of this
      nature have been constructed. Recently [Hoffman et al. (1996) J. Gen. Physiol.
      108, 295-313] we derived a series of true LR73/hu MDR 1 transfectants that are
      valuable for defining the MDR phenotype mediated by MDR protein alone, without
      the additional complexities introduced by exposing cells to chemotherapeutic
      drugs. Several independently derived clones from these and additional
      transfection experiments exhibit expression of MDR protein that is higher than
      that found in other true transfectants, and that is similar to the highest level
      of overexpression yet recorded for drug selected MDR cells. We examined altered
      Cl--dependent pHi regulation for these clones using improved single-cell
      photometry (SCP) techniques. Short-term isotonic Cl- substitution experiments
      performed in the presence of CO2/HCO3- reveal that mild overexpression of hu MDR
      1 protein alters anion exchange (Cl-/HCO3- exchange or AE) for LR73 cells, as
      expected on the basis of previous work [Luz et al. (1994) Biochemistry 33, 7239
      7249]. Interestingly, we now find that several independently selected high-level
      MDR 1 overexpressing clones acidify quite extensively upon isotonic exchange of
      Cl- and then rapidly alkalinize upon restoring normal [Cl-]. These data suggest
      that MDR protein may effectively compete against AE. The MDR protein effect is
      not dependent on HCO3-/CO2 or K+, is partially inhibited by verapamil, is
      completely inhibited by substituting K+ or N-methylglucamine (NMG+) for Na+ in
      the SCP perfusate but is not affected by 100 microM levels of amiloride,
      bumetanide, chlorothiazide, or stilbene. ATP depletion inhibits the MDR 1 effect.
      We are unable to restore normal AE activity for the MDR clones via manipulation
      of Cl- or HCO3- gradients. We thus suggest that MDR protein overexpression
      provides a novel Na+- and Cl--dependent pathway for transmembrane H+ transport.
      From analysis of ion dependency and inhibitor sensitivities, we conclude the
      transport is not via altered regulation of any known K+/H+, Na+/H+, or Cl-/HCO3-
      antiporters, Na+:K+:2Cl-, Na+:K+:2HCO3-, K+:HCO3-, or Na+:HCO3- co-transporters,
      or any combination of these. Thus, it appears to represent a novel ATP and Na+
      dependent Cl-/H+ antiport process that (1) may be directly mediated by the MDR
      protein, (2) may represent the modulation of one or more currently unidentified
      ion transport proteins by MDR protein, (3) may be due to some combination of
      direct ion transport and regulation of ion transport, or (4) may represent
      unusual passive H+ movement in response to a novel Cl--dependent electrical
      perturbation that occurs during our Cl- substitution protocol. The results have
      important implications for understanding drug resistance mediated by MDR 1
      overexpression, as well as the physiologic function of endogenously expressed MDR
      protein.

PMID- 9287159
TI  - Human MDR 1 protein overexpression delays the apoptotic cascade in Chinese
      hamster ovary fibroblasts.
AB  - Several laboratories have reported that overexpression of the multidrug
      resistance (MDR) protein is associated with intracellular alkalinization, and
      several investigators have reported that cells induced to undergo programmed cell
      death (apoptosis) acidify quite significantly. Because it is difficult to fully
      explain the resistance to apoptosis-inducing chemotherapeutic drugs that is
      exhibited by MDR tumor cells solely via altered drug transport alone [Hoffman et
      al. (1996) J. Gen. Physiol. 108, 295-313], we have investigated whether
      overexpression of the hu MDR 1 protein alters progression of the apoptotic
      cascade. LR73 fibroblasts induced to undergo apoptosis either via treatment with
      the chemotherapeutic drug colchicine or by serum withdrawal exhibit cellular
      volume changes, intracellular acidification, nuclear condensation, and
      chromosomal digestion ("ladder formation"), characteristic of apoptosis, in a
      temporally well-defined pattern. However, multidrug resistant LR73/20E or LR73/27
      hu MDR 1 transfectants recently created in our laboratory without selection on
      chemotherapeutic drug are significantly delayed in the onset of apoptosis as
      defined by the above criteria, regardless of whether apoptosis is induced by
      colchicine treatment or by serum withdrawal. Thus, the delay cannot simply be due
      to the well-known ability of MDR protein overexpression to lower chemotherapeutic
      drug accumulation in MDR cells. LR73/27V500 "selectants", exhibiting similar
      levels of MDR protein overexpression but higher multidrug resistance due to
      selection with the chemotherapeutic drug vincristine, exhibit a slightly longer
      delay in the progression of apoptosis. Normal apoptotic cascade kinetics are
      partially restored by pre-treatment of the MDR cells with the MDR protein
      inhibitor verapamil. Untransfected LR73 cells not expressing MDR protein but
      elevated in pHi via manipulation of CO2/HCO3- as described [Hoffman et al. (1996)
      J. Gen. Physiol. 108, 295-313] are inhibited in DNA ladder formation, similar to
      LR73/hu MDR 1 transfectants. These results uncover an additional mechanism
      whereby MDR protein overexpression may promote the survival of tumor cells and
      further support the notion that in some systems intracellular acidification may
      be either causal or permissive for proper progression of the apoptotic cascade.

PMID- 9287160
TI  - Conformations of primary amphipathic carrier peptides in membrane mimicking
      environments.
AB  - Two peptides designed for drug delivery were generated by the combination of a
      signal peptide with a nuclear localization sequence and are shown to facilitate
      the cellular internalization of small molecules which are covalently linked to
      these peptides. In order to understand the mechanism of internalization, the
      conformations of the peptides were investigated through different approaches both
      in solution and in membrane-mimicking environments. These peptides are highly
      versatile and adopt different conformational states depending on their
      environment. While in a disordered form in water, they adopt an alpha-helical
      structure in TFE and in the presence of micelles of SDS or DPC. The structured
      domain encompasses the hydrophobic part of the peptides, whereas the charged C
      termini remain unstructured. In contrast, in the presence of lipids and whatever
      the nature of the phosphate headgroup, the two peptides mainly adopt an
      antiparallel beta-sheet form and embed in the lipidic cores. This result suggests
      that the beta-sheet is responsible for the translocation through the cellular
      membranes but also questions the conformational state of signal peptides when
      associated to hydrophilic sequences.

PMID- 9287161
TI  - Structure and dynamics of the glucocorticoid receptor DNA-binding domain:
      comparison of wild type and a mutant with altered specificity.
AB  - Nuclear magnetic resonance was used to compare parameters reflecting solution
      structure and dynamics of the glucocorticoid receptor DNA-binding domain (GRDBD),
      which binds specifically to a GRE binding site on DNA, and a triple mutant
      (GRDBDEGA), which binds to an ERE site. The studies were prompted by an earlier
      observation that the cooperativity for dimeric DNA-binding is 10 times higher for
      the GRDBDEGA-ERE association than for the GRDBD-GRE association (Lundback et al.,
      1994). The higher binding cooperativity of the mutant was unexpected since the
      triple mutation (G458E, S459G, and V462A) is made in the recognition helix and
      distant from the dimerization surface which is formed by residues in the fragment
      A477-N491. Sequential and long-range NOE connectivities and measured 3JHNHalpha
      coupling constants indicate that the overall structures of the two proteins are
      very similar, possibly with a less well-defined structure of the fragment K486
      N491 in GRDBDEGA. However, chemical shift changes, line broadening, and increased
      amide proton exchange rates are observed for several residues at, or close to,
      the dimerization surface of the mutant. These observations are interpreted as a
      lower stability and/or several slowly interconverting folded conformations of
      this region of GRDBDEGA. The effects are likely to be due to the loss of a
      hydrogen bond which links S459 to the dimerization region in GRDBD. Different
      mechanisms for the increased binding cooperativity of the mutant are discussed,
      and it is noted that the properties of the GRDBDEGA dimerization region are
      reminiscent of those reported for the estrogen receptor DBD, which also binds to
      an ERE site.

PMID- 9287162
TI  - Spectroscopic effects of polarity and hydration in the distal heme pocket of
      deoxymyoglobin.
AB  - Distal pocket mutations at the E7 position (His64) of sperm whale deoxymyoglobin
      (deoxyMb) are used as a probe of distal pocket polarity and hydration. Changes of
      two key spectroscopic markers, the Fe-His(F8) stretch in the resonance Raman
      spectrum and the position of band III in the absorption spectrum, are monitored
      as the His64Tyr, His64Phe, His64Leu, and His64Gly mutations alter the distal heme
      pocket environment. The Fe-His vibration for the Phe, Leu, and Gly mutants is
      shifted to a lower frequency by 1-2 cm-1 relative to the Tyr mutant, wild type
      (WT), and native deoxyMb. Band III shifts to the red by approximately 4 nm (
      approximately 70 cm-1) relative to WT and native deoxyMb for all the His64
      mutants examined in this work. We correlate the small shift in the Fe-His
      frequency to the local electrostatic environment directly above the heme iron,
      affected by the presence of a localized water molecule in the heme pocket that is
      hydrogen-bonded to the E7 residue. The position of band III is roughly correlated
      to the displacement of the iron from the heme plane; however, the relatively
      large scatter in this correlation, as well as its dependence on distal pocket
      mutations, suggests that the heme pocket environment, particularly the E7
      residue, also affects the energy of this transition.

PMID- 9287163
TI  - Crystal structures of human DNA polymerase beta complexed with gapped and nicked
      DNA: evidence for an induced fit mechanism.
AB  - DNA polymerase beta (pol beta) fills single nucleotide (nt) gaps in DNA produced
      by the base excision repair pathway of mammalian cells. Crystal structures have
      been determined representing intermediates in the 1 nt gap-filling reaction of
      pol beta: the binary complex with a gapped DNA substrate (2.4 A resolution), the
      ternary complex including ddCTP (2.2 A), and the binary product complex
      containing only nicked DNA (2.6 A). Upon binding ddCTP to the binary gap complex,
      the thumb subdomain rotates into the closed conformation to contact the otherwise
      solvent-exposed ddCTP-template base pair. Thumb movement triggers further
      conformational changes which poise catalytic residue Asp192, dNTP, and template
      for nucleotidyl transfer, effectively assembling the active site. In the product
      nicked DNA complex, the thumb returns to the open conformation as in the gapped
      binary DNA complex, facilitating dissociation of the product. These findings
      suggest that pol beta may enhance fidelity by an induced fit mechanism in which
      correct base pairing between template and incoming dNTP induces alignment of
      catalytic groups for catalysis (via thumb closure), but incorrect base pairing
      will not. The structures also reveal that pol beta binds both gapped and nicked
      DNA with a 90 degrees kink occurring precisely at the 5'-phosphodiester linkage
      of the templating residue. If the DNA were not kinked in this way, contact
      between the thumb and dNTP-template base pair, presumably important for the
      checking mechanism, would be impossible, especially when the gap is but a single
      nucleotide. Such a 90 degrees kink may be a mechanistic feature employed by any
      polymerase involved in filling gaps to completion.

PMID- 9287164
TI  - Role of phospholipids in the protein stability of an insect lipoprotein,
      lipophorin from Rhodnius prolixus.
AB  - Lipophorin (Lp) is the major lipoprotein in insect hemolymph. The structural
      organization proposed for Lp is basically the same as that suggested for
      vertebrate lipoproteins, consisting of a hydrophobic core containing neutral
      lipids, stabilized in the aqueous environment by surrounding polar moieties of
      protein and phospholipids at the particle surface. After complete removal of
      phospholipids from Lp by phospholipase A2, the particle remains soluble [Gondim,
      K. C., Atella, G. C., Kawooya, J. K., & Masuda, H. (1992) Arch. Insect Biochem.
      Physiol. 20, 303-314]. However, studies on the roles of phospholipid on the
      structural stability of Lp are still lacking. In the present work, we have
      studied the structure and stability of dephospholipidated lipophorin (d-Lp).
      Trypsinolysis of d-Lp indicated no exposure of new cleavage sites on the protein
      when compared to Lp. However, an enhanced rate of proteolysis of the apoproteins
      (especially apolipophorin II) was observed in d-Lp. Circular dichroism analysis
      indicated that the secondary structure of Lp was not significantly affected by
      phospholipid removal. Furthermore, the exposure of tryptophan residues to the
      aqueous solvent in d-Lp was the same as in Lp, as indicated by intrinsic
      fluorescence emission spectra and fluorescence quenching experiments.
      Interestingly, d-Lp was more resistant to denaturation by guanidine hydrochloride
      than Lp. d-Lp was also found to be less sensitive than Lp to structural changes
      induced by hydrostatic pressure. Taken together, these results indicate that,
      although changes in its structural organization were subtle, dephospholipidated
      lipophorin may have additional protein-protein and/or protein-neutral lipid
      interactions that are responsible for the observed increase in stability.
      Therefore, phospholipids are not only not essential for Lp stability, but their
      presence in the particle seems to result in a less stable structure in the
      aqueous environment.

PMID- 9287165
TI  - Phosphoinositide-specific phospholipase C delta1 activity toward micellar
      substrates, inositol 1,2-cyclic phosphate, and other water-soluble substrates: a
      sequential mechanism and allosteric activation.
AB  - The kinetics of full-length and PH domain truncated cloned PI-PLC delta1 from rat
      toward soluble substrates [inositol 1, 2-(cyclic)-phosphate (cIP) and
      glycerophosphoinositol phosphates (GPIPx)] as well as PI in detergent micelles
      provide the following insights into the mechanism of this enzyme. (i) That cIP is
      a substrate for the enzyme implies a two-step mechanism for PI hydrolysis
      [intramolecular phosphotransferase reaction to form cIP followed by cyclic
      phosphodiesterase activity to form inositol-1-phosphate (I-1-P)]. The dependence
      of enzyme activity on cIP is sigmoidal, suggesting a transition between less
      active and more active forms of the enzyme that is affected by substrate. (ii)
      Interfaces increase the kcat for cIP (but do not affect the cooperativity), and
      this allosteric activation requires an intact PH domain. (iii) Phosphorylation of
      the soluble inositol phosphodiesters GPI, GPIP, and GPIP2 enhances PI-PLC delta1
      activity by dramatically increasing kcat and decreasing Km. For these
      phosphodiesters, the substrate saturation curve is no longer sigmoidal but
      hyperbolic, indicating the phosphorylated substrate can shift the enzyme to the
      activated form. (iv) Given the kinetic parameters for cIP hydrolysis and the
      constant ratio of cIP/I-1-P generated during PI hydrolysis, the cIP produced in
      situ is either released (and not readily rebound since its concentration is well
      below Km) or attacked by a water molecule for the generation of the acyclic
      product.

PMID- 9287166
TI  - Role of deprotonation events in ubihydroquinone:cytochrome c oxidoreductase from
      bovine heart and yeast mitochondria.
AB  - The pH dependence of bovine and yeast cytochrome bc1 complex catalyzing electron
      transfer from ubi- and plastohydroquinone to cytochrome c have been analyzed. The
      pH dependence of the steady-state rate was found to be governed by two protonable
      groups, one of which (pK approximately 6.6) has to be deprotonated while the
      other (pK approximately 9.2) has to be protonated to allow catalysis. Using
      ubideuteroquinone instead of ubihydroquinone as a substrate resulted in 1.4- and
      1.7-fold lower steady-state rates for the bovine and yeast enzymes, respectively.
      The activation energy at pH 8.0 was 33 kJ/mol for the bovine and 44 kJ/mol for
      the yeast enzyme and exhibited a linear decrease between pH 5.4 and 9.2. For
      ubihydroquinone the slope was very close to a value of -5.7 kJ/mol expected if
      the activation energy depended on a single deprotonation event. When
      plastohydroquinone was used instead, the slope more than doubled, indicating that
      a second deprotonation contributed to the activation barrier with this
      nonphysiological substrate. In contrast to previous kinetic models for the
      cytochrome bc1 complex, which propose that the activation barrier is associated
      with the formation of ubisemiquinone at the ubihydroquinone oxidation center, our
      results strongly suggest that the best approximation of the transition state is
      the singly deprotonated form of ubihydroquinone. This supports the recently
      proposed proton-gated charge transfer mechanism, which has control of catalysis
      by the first deprotonation of ubihydroquinone as one of its key features [Brandt,
      U. (1996) FEBS Lett. 387, 1-6]. All results reported here can be rationalized in
      a straightforward way based on other aspects of the same hypothesis.

PMID- 9287167
TI  - Mechanism of carbon monoxide oxidation by the carbon monoxide
      dehydrogenase/acetyl-CoA synthase from Clostridium thermoaceticum: kinetic
      characterization of the intermediates.
AB  - Carbon monoxide dehydrogenase/acetyl-CoA synthase (CODH/ACS) from Clostridium
      thermoaceticum catalyzes (i) the synthesis of acetyl-CoA from a methylated
      corrinoid protein, CO, and coenzyme A and (ii) the oxidation of CO to CO2. CO
      oxidation occurs at a Ni- and FeS-containing center known as cluster C. Electrons
      are transferred from cluster C to a separate metal center, cluster B, to external
      acceptors like ferredoxin. In the work described here, we performed reductive
      titrations of CODH/ACS with CO and sodium dithionite and monitored the reaction
      by electron paramagnetic resonance (EPR) spectroscopy. We also performed pre
      steady-state kinetic studies by rapid freeze-quench EPR spectroscopy (FQ-EPR) and
      stopped-flow kinetics. Redox titrations of CODH/ACS revealed the existence of a
      UV-visible and EPR-silent electron acceptor denoted center S that does not appear
      to be associated with any of the other metal centers in the protein. Our results
      support the previous proposals [Anderson, M. E., & Lindahl, P. A. (1994)
      Biochemistry 33, 8702-8711; Anderson, M. E., & Lindahl, P. A. (1996) Biochemistry
      35, 8371-8380] that the Cred2 form of cluster C is two electrons more reduced
      than the Cred1 form. The combined results from titrations and pre-steady-state
      studies were used to formulate a mechanism for CO oxidation, composed of the
      following steps: (i) CO binding to the [Cred1,Box, Xox] state to yield a Cred1-CO
      complex; (ii) two-electron reduction of Cred1 to Cred2 concerted with CO2
      release; (iii) binding of a second CO molecule to the [Cred2,Box,Xox] state to
      form a Cred2-CO complex; (iv) electron transfer from Cred2-CO to cluster B to
      form [Cred2,Bred,Xred] with concerted release of the second CO2. Step iii
      competes with internal electron transfer from Cred2 to Box and Xox. At high CO
      concentrations, step iii is favored, whereas at low concentrations, only one CO
      molecule per turnover binds and undergoes oxidation. Closure of the catalytic
      cycle involves electron transfer from reduced enzyme to an electron acceptor
      protein, like ferredoxin. Xox is a yet-uncharacterized electron acceptor that may
      be an intermediate in the reduction of center S. The Cred2 state appears to be
      the predominant state of cluster C during steady-state turnover. The rate
      determining step for the first half-reaction is step iv, while during steady
      state turnover, it appears to be electron transfer to external electron
      acceptors.

PMID- 9287168
TI  - Mechanism-based phage display selection of active-site mutants of human
      glutathione transferase A1-1 catalyzing SNAr reactions.
AB  - A library of active-site mutants has been constructed by targeting selected amino
      acid residues in human glutathione transferase (GST) A1-1 for random mutagenesis.
      The mutated residues are suitably positioned for interaction with the second,
      electrophilic substrate, in particular chloronitrobenzene derivatives undergoing
      SNAr reactions. DNA representing the GST A1-1 mutant library was fused with DNA
      encoding gene III protein, a component of the coat of filamentous phage. Phage
      display was used for affinity selection of GST A1-1 mutants with altered
      catalytic properties. The affinity ligand used was the sigma-complex of 1,3,5
      trinitrobenzene and glutathione immobilized to Sepharose. The complex was
      designed to mimic the transition state of SNAr reactions catalyzed by GSTs. The
      selection system is based on the combination of affinity for the sigma-complex as
      well as the ability to promote its formation, thus mimicking two salient features
      of the assumed catalytic mechanism for the SNAr reactions. Many of the GST A1-1
      mutants selected and analyzed contained an aromatic amino acid residue in one of
      the mutated positions, suggesting favorable interactions with the
      trinitrocyclohexadienate moiety of the affinity ligand. A mutant C36 was selected
      for more detailed studies. Its catalytic efficiency with several
      chloronitrobenzene substrates was 20-90-fold lower than that of wild-type GST A1
      1, but fully comparable to naturally evolved GSTs of different classes, providing
      a 10(5)-fold rate enhancement over the uncatalyzed reaction. In the conjugation
      of ethacrynic acid, a Michael addition reaction, mutant C36 was 13-fold more
      efficient than the wild-type enzyme. Within experimental error, the quotient
      between the KF values for wild-type GST A1-1 and mutant C36 is the same as that
      between the kcat/KM values determined with 1-chloro-2,4-dinitrobenzene for the
      two enzyme forms. This result indicates that sigma-complex formation is rate
      limiting for the catalyzed reaction. Thus, the principle of transition-state
      stabilization as a component of catalysis has been successfully exploited in
      affinity selection of catalytically competent GST A1-1 mutants. This mechanism
      based procedure also selects for the ability to promote sigma-complex formation,
      and serves as a probe of the catalytic mechanism.

PMID- 9287169
TI  - Design and characterization of a multisite fluorescence energy-transfer system
      for protein folding studies: a steady-state and time-resolved study of yeast
      phosphoglycerate kinase.
AB  - A multisite distance-based fluorescence resonance energy-transfer assay system
      was developed for the study of protein folding reactions. Single- and double
      cysteine substitution mutagenesis was utilized to place sulfhydryl residues
      throughout the tertiary structure of the bidomain enzyme yeast phosphoglycerate
      kinase (PGK). These reactive cysteines were covalently modified with extrinsic
      donor [5-[[2-(2-iodoacetamido)ethyl]amino]-1-naphthalenesulfonic acid] and
      acceptor (5-iodoacetamidofluorescein) fluorescent labels. A detailed experimental
      strategy was followed, which revealed that, when these relatively large extrinsic
      fluorescent labels are covalently attached to properly selected solvent-exposed
      residues, they do not affect the intrinsic stability of the protein. The PGK
      crystal structure was combined with molecular dynamics simulations of the dyes
      built into the protein and time-resolved anisotropy experiments, in order to
      estimate a more realistic orientation factor, <kappa2>*, for each donor/acceptor
      pair. Time-resolved and steady-state fluorescence energy-transfer experiments
      revealed that this distance assay, spanning six different donor-acceptor
      distances, is linear and accurate (to within 10-20%) over the range of 30-70 A.
      This distance assay system for PGK allows for the measurement of long-range
      changes in intra- and interdomain spatial organization during protein folding
      reactions. The approach which we have developed can be applied to any protein
      system in which unique one- and two-site cysteine residues can be engineered into
      a protein. In the following paper [Lillo, M. P., et al. (1997) Biochemistry 36,
      11273-11281], these multisite energy-transfer pairs are utilized for stopped-flow
      unfolding studies.

PMID- 9287170
TI  - Real-time measurement of multiple intramolecular distances during protein folding
      reactions: a multisite stopped-flow fluorescence energy-transfer study of yeast
      phosphoglycerate kinase.
AB  - Understanding the set of rules which dictate how the primary amino acid sequence
      determines tertiary structure is an unsolved problem in biophysics. If it were
      possible to simultaneously measure all of the intramolecular distances in a
      protein (in real time) during a folding reaction, the "second" genetic code
      problem would be solved. Regrettably, no such technique currently exists. As a
      first step toward this goal, an optical distance assay system has been developed
      for a two-domain protein, yeast phosphoglycerate kinase (PGK), using Forster
      resonance energy transfer [Lillo, M. P., et al. (1997) Biochemistry 36, 11261
      11272]. In this study, real-time stopped-flow distance changes are measured using
      six unique pairs of donor/acceptor fluorescent labels strategically placed
      throughout the tertiary structure of PGK. These multiple donor/acceptor sites
      were genetically engineered into PGK by cysteine substitution mutagenesis
      followed by extrinsic labeling with fluorescent probes, 5-[[[(2
      iodoacetyl)amino]ethyl]amino]naphthalenesulfonic acid (as a donor) and 5
      iodoacetamidofluorescein (acceptor). The unfolding of PGK is found to be a
      sequential multistep process (native --> I1 --> I2 --> unfolded) with rate
      constants of 0.30, 0.16, and 0.052 s-1, respectively (from native to unfolded).
      Unique to this unfolding study, six intramolecular distance vectors have been
      resolved for both the I1 and I2 states. With this distance information, it is
      shown that the transition from the native to I1 state can be modeled as a large
      hinge-bending motion, in which both domains "swing away" from each other by about
      15 A. As the domains move apart, the carboxyl-terminal domain rotates almost 90
      degrees about the hinge region connecting the two domains. It is also shown that
      the amino-terminal domain remains intact during the native --> I1 transition,
      consistent with our previous site-specific tryptophan fluorescence anisotropy
      stopped-flow study [Beechem, J. M., et al. (1995) Biochemistry 34, 13943-13948].
      Future experiments are proposed which will attempt to resolve in detail the
      unfolding/refolding transitions in this protein with a resolution of
      approximately 5-10 A.

PMID- 9287171
TI  - The role of betaArg-10 in the B800 bacteriochlorophyll and carotenoid pigment
      environment within the light-harvesting LH2 complex of Rhodobacter sphaeroides.
AB  - Previous work has suggested that the betaArg-10 residue forms part of the binding
      site for the B800 bacteriochlorophyll in the LH2 complex of
      Rhodobactersphaeroides [Crielaard, W., Visschers, R. W., Fowler, G. J. S., van
      Grondelle, R., Hellingwerf, K. J., Hunter, C. N. (1994) Biochim. Biophys.
      Acta1183, 473-482], and this is consistent with the X-ray crystallographic data
      that have been subsequently obtained for the related LH2 complex from
      Rhodopseudomonas acidophila [McDermott, G., Prince, S. M., Freer, A. A.,
      Hawthornthwaite-Lawless, A. M., Papiz, M. Z., Cogdell, R. J., Isaacs, N. W.
      (1995) Nature 374, 517-521]. Therefore, in order obtain more information about
      the B800 binding site and its effect on the B800 absorption band, betaArg-10 was
      replaced by residues Met, His, Asn, Leu, and Lys (in addition to the Glu mutant
      described in our previous work); these residues were thought to represent a
      suitable range of amino acid shape, charge, and hydrogen-bonding ability. This
      new series of betaArg-10 mutants, in the form of LH2 complexes in the native
      membrane, has been characterized using a variety of biochemical and spectroscopic
      techniques in order to determine the ways in which the mutants differ from wild
      type (WT) LH2. For example, most of the mutant LH2 complexes were found to have
      blue-shifted B800 absorption bands ranging from 794 to 783 nm at 77 K; the
      exception to this trend is the betaArg-10 to Met mutant, which absorbs maximally
      at 798 nm. These blue shifts decrease the spectral overlap between the "B800" and
      B850 pigments, which allowed us to examine the nature of the B800 to B850
      transfer step for the betaArg-10 mutant LH2 complexes by carrying out a series of
      room temperature subpicosecond energy transfer measurements. The results of these
      measurements demonstrated that the reduced overlap leads to a slower B800 to B850
      transfer, although the alterations at betaArg-10 were found to have little effect
      on the efficiency of internal energy transfer within LH2. Similarly, carotenoid
      to bacteriochlorophyll energy transfer was largely unaffected, although shifts in
      the excitation spectra in the carotenoid region were noted. These betaArg-10
      mutant complexes provide an opportunity to investigate the structural
      requirements for the binding of monomeric bacteriochlorophyll and to examine the
      basis of the red shift seen for bacteriochlorophyll in photosynthetic complexes,
      in addition to providing new information about the environment of the carotenoid
      pigments in this complex.

PMID- 9287172
TI  - Co-receptors for HIV-1 entry.
AB  - HIV-1 enters its target cells by fusion at the plasma membrane. The primary
      cellular receptor for HIV is CD4, but this molecule is insufficient to permit
      viral fusion. During 1996, the necessary entry co-factors (co-receptors or second
      receptors) were identified as being members of the seven-transmembrane-spanning
      receptor family fusin: CXCR4 for T-tropic strains and CCR5, principally, for M
      tropic strains. The co-receptor functions of these proteins are inhibited by
      their natural alpha- and beta-chemokine ligands.

PMID- 9287173
TI  - Recombinant viruses as vaccines and immunological tools.
AB  - Recombinant viruses have been investigated as candidate vaccines, and have also
      been used extensively as immunological tools. Recent advances in this area
      include the following: the construction and testing of a recombinant simian
      immunodeficiency virus encoding human interferon-gamma; the development of new
      vectors such as recombinant poliovirus; and the generation of polyepitope
      vaccines. Basic immunological research has benefited from the use of recombinant
      viruses to further understand the role of molecules such as CD40 ligand, nitric
      oxide and interleukin-4.

PMID- 9287174
TI  - Immunobiology of Helicobacter pylori infection.
AB  - Helicobacter pylori is a 'slow' bacterial pathogen. While infection is usually
      acquired early in life, only decades later does severe pathology appear. During
      this long period of incubation, the host mounts a vigorous immune response
      against H. pylori which fails to resolve the infection and may in fact contribute
      to the severity of the disease. In the past year, evidence has accumulated
      indicating a role for a polarized T helper 1 cell response in the gastric
      pathology induced by H. pylori. Furthermore, a pathogenicity island in type I H.
      pylori strains has been shown to be responsible for H. pylori induced
      inflammation. Recent advances in animal models have provided the rationale for
      entering into human clinical trials of an H. pylori vaccine

PMID- 9287175
TI  - The role of Jak3 in lymphoid development, activation, and signaling.
AB  - Mutations in a number of lymphoid signaling molecules lead to immunodeficiencies
      in mice and humans. Among these, one very pleiotropic syndrome results from
      deficiencies in an array of cytokine signaling pathways utilizing a cytokine
      receptor common gamma chain, gammac, and the tyrosine kinase Jak3. Recent
      advances in our understanding of the role of gammac and Jak3 in lymphocyte
      development and function highlight the importance of cytokine receptor signaling
      pathways in regulating lymphoid homeostasis and responsiveness.

PMID- 9287176
TI  - Early responses to infection: chemokines as mediators of inflammation.
AB  - Chemokines are a superfamily of small related protein molecules that are secreted
      by a variety of cells and that have, among their diverse biological properties,
      the ability to recruit a wide range of immune cells to the sites of infection and
      disease. Chemokines are secreted in response to bacterial, viral, parasitic, and
      mycobacterial pathogens. Our recent progress in understanding the patterns of
      chemokine secretion in response to various pathogens and their impact on disease
      manifestations is likely to lead to the development of novel therapeutic
      approaches for a variety of serious infections.

PMID- 9287177
TI  - Immune reconstitution in HIV infection.
AB  - Progressive immune deficiency arising during HIV disease reflects the continual
      degradation and the ultimate deletion of immune specificites defined by the
      CD4(+) T lymphocyte repertoire. Recent evidence suggests that improvements in the
      immune function of patients with HIV who receive therapy primarily reflects the
      expansion of CD4(+) T lymphocyte populations present before therapy commenced.
      These observations have implications for clinical management, therapeutic
      strategies, and future research.

PMID- 9287178
TI  - The T cell response against fungal infections.
AB  - A variety of pathological conditions, including impaired immune function, is
      believed to underlie host susceptibility to fungal infections and to determine
      both the severity and the characteristic of the associated pathology. Although
      the redundancy and the interdependence of antifungal responses may not favor the
      proper dissection and appreciation of individual effector mechanisms, the T
      helper type 1/type 2 paradigm of acquired immunity to fungi is proving essential
      for a better understanding of the host response from a regulatory perspective.
      The recent understanding of the importance of the different T helper cell subsets
      in fungal infections and the increasing appreciation of the reciprocal regulation
      between the innate, humoral, and adaptive immune systems in the development of
      optimal antimicrobial immunity have offered us new clues which may lead to an
      understanding of T cell dependent immunity to fungi.

PMID- 9287179
TI  - Alternative antigen processing pathways in anti-infective immunity.
AB  - Proteinaceous and nonproteinaceous antigens from exogenous microorganisms can be
      processed by the host for MHC class I restricted presentation to T cells.
      Macrophages, B cells, mast cells and dendritic cells are antigen-presenting cells
      that process such exogenous antigens through multiple pathways before MHC
      restricted epitope presentation. New conceptual frameworks are emerging regarding
      the processing and presentation to T cells of peptide or nonpeptide epitopes from
      bacteria in the context of conventional MHC class I molecules, nonconventional
      MHC class I molecules, or CD1 molecules. Animal experiments have demonstrated
      that these pathways are of central importance for generating protective
      antibacterial T cell responses. These findings form the basis for new vaccine
      designs that specifically target MHC class I restricted T cell reactivity.

PMID- 9287180
TI  - Interference with antigen processing by viruses.
AB  - Viruses that establish persistent infections in their host, such as
      herpesviruses, adenoviruses or HIV, express proteins designed to pre-empt or
      evade recognition and elimination by MHC class I restricted CD8+ T lymphocytes.
      Notable discoveries during the annual period of review have demonstrated that, in
      principle, each single step within the MHC class I pathway of antigen processing
      and presentation is fair game for manipulation by viral functions. The viral
      factors that are natural inhibitors of this pathway have been instrumental for
      the elucidation of the distinct molecular mechanisms that are exploited by
      viruses. The viral stealth strategies that downregulate MHC class I protein
      surface expression may lead, however, to a higher susceptibility of virus
      infected cells to natural killer cell activity. Strikingly, there is evidence
      that some viruses counteract increased natural killer cell recognition by
      expressing viral MHC class I homologues that function as surrogate inhibitors of
      natural killer cell activity.

PMID- 9287181
TI  - HIV. A clever hijacker of the immune system.

PMID- 9287182
TI  - Immunity to infection.

PMID- 9287183
TI  - Genetic effects on immunity. Protein tyrosine kinases: disease loci for inherited
      immunodeficiencies.

PMID- 9287184
TI  - The CD40-CD154 system in anti-infective host defense.
AB  - Research in the past few years has documented significant advances in our
      understanding of the CD40-CD40 ligand (CD154) system in diverse immune functions.
      This system influences many T cell mediated inflammatory immune responses and
      effector functions, unmasking a previously unexpected role for CD40-CD154 in cell
      mediated immunity. Manipulation of CD154 in animal models of infection by the use
      of CD154-deficient mice or anti-CD154 antibodies has shown the importance of this
      system in the initiation of the inflammatory response, in the activation of
      antigen-presenting cells and in resistance to infections.

PMID- 9287185
TI  - The role of CD1 molecules in immune responses to infection.
AB  - Recent work on CD1 molecules has demonstrated that human CD1b and a lipoglycan
      from mycobacteria that CD1b presents colocalize to late endosomes. Presentation
      of this lipoglycan by CD1b requires antigen uptake via the mannose receptor.
      CD8(+) CD1-restricted T cells can decrease the load of intracellular mycobacteria
      by granule release. TCR-transgenic and CD1-deficient mice have provided insights
      into the role of CD1 in the T helper responses required for the clearance of some
      microorganisms.

PMID- 9287186
TI  - Role of Btk in B cell development and signaling.
AB  - Bruton's tyrosine kinase (Btk), the target of inactivating mutations in X-linked
      immunodeficiency diseases of mice and humans, is essential for normal B cell
      responsiveness. Recent studies have outlined a mechanism for the activation of
      Btk by B cell receptor engagement and have identified proximal and distal targets
      of Btk action.

PMID- 9287187
TI  - Tuning into immunological dissonance: an experimental model for infectious
      mononucleosis.
AB  - Virus infections cause a much more profound perturbation of the lymphoid tissue
      than can be accounted for by the exigencies of the antigen-specific response. The
      extent of this 'immunological dissonance' is seen most dramatically in mice
      infected with a persistent gamma-herpesvirus, MHV-68. A profile of massive,
      continuing proliferation of both T and B cells in the lymph nodes and spleen
      leads to a dramatic increase in the prevalence of a CD62Llow CD8+ T cell subset
      in the blood, a pattern first detected two to three weeks after intranasal
      exposure to the inducing virus. This syndrome, which seems identical to human
      infectious mononucleosis (IM), persists for a further month or more. Part of the
      IM-like phase of MHV-68 infection reflects the selective expansion of Vbeta4+
      CD8+ T cells, with the Vbeta4 effect being apparent for several different MHC
      class I H-2 types but not in mice that are deficient in MHC class II glycoprotein
      expression. Depleting CD4(+) T helper cells in MHV-68-infected mice leads to the
      decreased proliferation of the CD8+ T cells in the spleen and fewer CD62Llow CD8+
      T lymphocytes than would be expected in peripheral blood, but fails to diminish
      the prominence of the V4beta+ CD8+ population. The results so far of this unique
      experimental mouse model of IM suggest that both cytokine-mediated effects and a
      viral superantigen are operating to promote the dramatic expansion and
      persistence of activated CD8+ T cells in the vascular compartment.

PMID- 9287188
TI  - Protein tyrosine kinases in thymocyte development.
AB  - Much has been learned over the past few years about how protein tyrosine kinases
      mediate pre-TCR and mature alphabetaTCR function. The highlights include
      understanding the roles and the distinct effects of the Src and Syk families of
      protein tyrosine kinases in thymocyte development and function.

PMID- 9287189
TI  - Role of dendritic and follicular dendritic cells in HIV infection and
      pathogenesis.
AB  - Dendritic cells (DCs) and follicular dendritic cells (FDCs) play important roles
      in HIV-mediated pathogenesis. Recent studies have defined new DC subsets and
      shown that DCs in lymphoid mucosa can both harbor virus and stimulate its spread
      into CD4(+) T cells. FDCs harbor unspliced HIV mRNA and immune complexed virus,
      but not actively infectious virus, yet these cells are a key regulated reservoir
      of virions.

PMID- 9287191
TI  - Immunology on the Internet.

PMID- 9287190
TI  - The impact of host genetics on susceptibility to human infectious diseases.
AB  - The development of genetic epidemiology methods using recent human genetic
      mapping information, together with the growing availability of candidate genes,
      has led to major advances in the identification of host genes involved in human
      infectious diseases. Within the past year, highlights include the mapping of a
      locus controlling the intensity of infection by Schistosoma mansoni, the
      demonstration that mutations in the interferon-gamma receptor 1 gene are
      causative of disseminated infection due to weakly pathogenic mycobacteria, and
      the identification, in the CCR5 gene, of a deletion which provides high
      protection against HIV-1 infection. The impact of these findings on the
      understanding of infectious disease pathogenesis and on the design of future
      preventive and therapeutic strategies should be considerable.

PMID- 9287192
TI  - Web alert. Immunity to infection. Genetic effects on immunity. HIV.

PMID- 9287194
TI  - Cellular mechanisms for preservation of timing in central auditory pathways.
AB  - The faithful preservation of acoustic timing information, as signals are passed
      from one synaptic level to another, requires a convergence of morphological,
      biophysical, and biochemical specializations in auditory neurons. Recent studies
      have focused on the adaptive membrane properties of neurons in the auditory
      brainstem. These include analyses of neurotransmitter receptors and voltage-gated
      channels, as well as the mechanisms of transmitter release and its modulation.
      The molecular composition of the relevant proteins are now being demonstrated,
      including the glutamate receptor Dflop (GluR-Dflop) subunit of AMPA receptors and
      members of the Kv1 and Kv3 families of potassium channels.

PMID- 9287193
TI  - Activation and inactivation steps in the visual transduction pathway.
AB  - Recent genetic, biochemical and electrophysiological evidence has provided
      insights into the molecular identity of the substance responsible for bleaching
      desensitization in vision. Studies examining the molecular defects that cause
      delayed dark adaptation suggest that the desensitizing substance is recognized by
      rhodopsin kinase and/or arrestin and, therefore, is probably a complex comprising
      all-trans-retinal and opsin.

PMID- 9287195
TI  - Sensory hyperacuity in the jamming avoidance response of weakly electric fish.
AB  - Sensory systems often show remarkable sensitivities to small stimulus parameters.
      Weakly electric fish are able to resolve intensity differences of the order of
      0.1% and timing differences of the order of nanoseconds during an electrical
      behavior, the jamming avoidance response. The neuronal origin of this
      extraordinary sensitivity is being studied within the exceptionally well
      understood central mechanisms of this behavior.

PMID- 9287196
TI  - Olfactory processing: maps, time and codes.
AB  - Natural odors are complex, multidimensional stimuli. Yet, they are learned and
      recognized by the brain with a great deal of specificity and accuracy. This
      implies that central olfactory circuits are optimized to encode these complex
      chemical patterns and to store and recognize their neural representations. What
      shape this optimization takes remains somewhat mysterious. Recent results from
      studies focusing on odor representation in the first olfactory relay (i.e. one
      synapse downstream of the receptor neurons) suggest a great deal of order and
      precision in the spatial and temporal features of odor representation. Whether
      these spatio-temporal features of neural activity are an essential part of the
      code for odors (i.e. whether these features are essential for the downstream
      decoding circuits) remains a central issue.

PMID- 9287197
TI  - What fMRI has taught us about human vision.
AB  - The recent application of functional magnetic resonance imaging (fMRI) to visual
      studies has begun to elucidate how the human visual system is anatomically and
      functionally organized. Bottom-up hierarchical processing among visual cortical
      areas has been revealed in experiments that have correlated brain activations
      with human perceptual experience. Top-down modulation of activity within visual
      cortical areas has been demonstrated through studies of higher cognitive
      processes such as attention and memory.

PMID- 9287198
TI  - Parietal cortex: from sight to action.
AB  - Recent findings have altered radically our thinking about the functional role of
      the parietal cortex. According to this view, the parietal lobe consists of a
      multiplicity of areas with specific connections to the frontal lobe. These areas,
      together with the frontal areas to which they are connected, mediate distinct
      sensorimotor transformations related to the control of hand, arm, eye or head
      movements. Space perception is not unitary, but derives from the joint activity
      of the fronto-parietal circuits that control actions requiring space computation.

PMID- 9287199
TI  - Mechanical amplification of stimuli by hair cells.
AB  - Unlike any other known sensory receptor, the hair cell uses positive feedback to
      augment the stimulus to which it responds. In the internal ears of many
      vertebrates, hair cells amplify the inputs to their mechanosensitive hair
      bundles. Outer hair cells of the mammalian cochlea display a unique form of
      somatal motility that may underlie their contribution to amplification. In other
      receptor organs, hair cells may effect amplification by hair-bundle movements
      driven by the activity of myosin or of transduction channels. Recent work has
      demonstrated the presence of several myosin isozymes in hair bundles, confirmed
      that bundles display myosin ATPase activity, and shown that the work performed by
      myosin molecules could account for one aspect of the amplificatory process.

PMID- 9287200
TI  - Peripheral pain mechanisms.
AB  - Our understanding of the cellular and molecular bases of transduction of painful
      stimuli has burgeoned in the past year, mainly as a result of studies on isolated
      sensory neurones in culture. The ion channels underlying neuronal responses to
      noxious heat, to protons and to ATP have recently been characterized. The typical
      increase in nociceptor sensitivity produced by tissue damage has been found to be
      mediated by at least two distinct mechanisms. In the first, bradykinin augments
      the current activated by heat through a mechanism that involves activation of
      protein kinase C. In a second sensitization mechanism, prostaglandin E2 alters
      the voltage threshold of several ion channels, including a novel tetrodotoxin
      insensitive Na+ channel, in such a way that initiation of action potentials is
      facilitated.

PMID- 9287201
TI  - Insect visual perception: complex abilities of simple nervous systems.
AB  - Despite their relatively simple nervous systems, insects display a rich
      behavioural repertoire, in which vision plays a major role. In the past two
      years, much knowledge has been gained about how insects are capable of a variety
      of flexible, visually guided tasks that involve a high level of complexity. From
      long-range navigation to median-range orientation and close-up recognition,
      insects apply different strategies that complement each other, that are used
      sequentially during their approach flight towards their goals, and that may
      replace each other, depending on the salience of, and the attention towards,
      particular visual cues.

PMID- 9287202
TI  - Learning perceptual skills: behavioral probes into adult cortical plasticity.
AB  - Recent studies of the improvement of perceptual performance as a function of
      training - perceptual learning - have provided new insights into the neuronal
      substrates of this type of skill learning in the adult brain. Issues such as
      where in the brain, when and under what conditions practice-related changes occur
      are under investigation. The results of these studies suggest that a behaviorally
      relevant degree of plasticity is retained in the adult cortex, even within early,
      low-level representations in sensory and motor processing streams. The
      acquisition and retention of skills may share many characteristics with the
      functional plasticity subserving early-life learning and development. While the
      specificity of learning provides localization constraints, an important clue to
      the nature of the underlying neuronal changes is the time course of learning.

PMID- 9287203
TI  - New perspectives on the mechanisms for orientation selectivity.
AB  - Since the discovery of orientation selectivity by Hubel and Wiesel, the
      mechanisms responsible for this remarkable operation in the visual cortex have
      been controversial. Experimental studies over the past year have highlighted the
      contribution of feedforward thalamo-cortical afferents, as proposed originally by
      Hubel and Wiesel, but they have also indicated that this contribution alone is
      insufficient to account for the sharp orientation tuning observed in the visual
      cortex. Recent advances in understanding the functional architecture of local
      cortical circuitry have led to new proposals for the involvement of intracortical
      recurrent excitation and inhibition in orientation selectivity. Establishing how
      these two mechanisms work together remains an important experimental and
      theoretical challenge.

PMID- 9287204
TI  - Mechanisms of visual object recognition: monkey and human studies.
AB  - The feature-based representations of object images in the inferotemporal cortex
      of macaque monkeys have been further characterized by optical imaging
      experiments. Recently, the close correlation between the activity of
      inferotemporal cells and the perception of object images has been revealed by
      single-unit recordings from behaving monkeys. The human homologue of the monkey
      inferotemporal cortex has been identified through use of new non-invasive
      techniques.

PMID- 9287206
TI  - Sensory systems. Editorial overview.

PMID- 9287205
TI  - Synchronous oscillatory activity in sensory systems: new vistas on mechanisms.
AB  - The origin and nature, as well as the functional role, of synchronous oscillatory
      activity in the cortex are among the major unresolved issues in systems
      neurobiology. Recent advances in understanding the mechanisms underlying
      oscillations include the description of intrinsically bursting pyramidal cells in
      striate cortex in vivo and the discovery of inhibitory interneurons that fire
      spike doublets to induce synchrony. The behavioral consequences of coordinated
      activity in cortical neurons remain poorly understood.

PMID- 9287207
TI  - Genomic imprinting in the brain.
AB  - Human genetic studies have directed attention to genetic imprinting in a number
      of syndromes involving brain dysfunction, such as Prader-Willi syndrome, Angelman
      syndrome, Turner's syndrome, bipolar depression and schizophrenia. Molecular
      genetics is providing insights into the complexity of these imprinting
      mechanisms, while experimental studies are revealing the differential roles that
      maternal and paternal genomes may play in brain development and growth.

PMID- 9287208
TI  - Web alert. Sensory systems.

PMID- 9287210
TI  - STATs and gene regulation.
AB  - STATs (signal transducers and activators of transcription) are a family of latent
      cytoplasmic proteins that are activated to participate in gene control when cells
      encounter various extracellular polypeptides. Biochemical and molecular genetic
      explorations have defined a single tyrosine phosphorylation site and, in a
      dimeric partner molecule, an Src homology 2 (SH2) phosphotyrosine-binding domain,
      a DNA interaction domain, and a number of protein-protein interaction domains
      (with receptors, other transcription factors, the transcription machinery, and
      perhaps a tyrosine phosphatase). Mouse genetics experiments have defined crucial
      roles for each known mammalian STAT. The discovery of a STAT in Drosophila, and
      most recently in Dictyostelium discoideum, implies an ancient evolutionary origin
      for this dual-function set of proteins.

PMID- 9287216
TI  - Requirement for GD3 ganglioside in CD95- and ceramide-induced apoptosis.
AB  - Gangliosides participate in development and tissue differentiation. Cross-linking
      of the apoptosis-inducing CD95 protein (also called Fas or APO-1) in lymphoid and
      myeloid tumor cells triggered GD3 ganglioside synthesis and transient
      accumulation. CD95-induced GD3 accumulation depended on integral receptor "death
      domains" and on activation of a family of cysteine proteases called caspases.
      Cell-permeating ceramides, which are potent inducers of apoptosis, also triggered
      GD3 synthesis. GD3 disrupted mitochondrial transmembrane potential (DeltaPsim),
      and induced apoptosis, in a caspase-independent fashion. Transient overexpression
      of the GD3 synthase gene directly triggered apoptosis. Pharmacological inhibition
      of GD3 synthesis and exposure to GD3 synthase antisense oligodeoxynucleotides
      prevented CD95-induced apoptosis. Thus, GD3 ganglioside mediates the propagation
      of CD95-generated apoptotic signals in hematopoietic cells.

PMID- 9287217
TI  - A broad-spectrum chemokine antagonist encoded by Kaposi's sarcoma-associated
      herpesvirus.
AB  - Kaposi's sarcoma-associated herpesvirus encodes a chemokine called vMIP-II. This
      protein displayed a broader spectrum of receptor activities than any mammalian
      chemokine as it bound with high affinity to a number of both CC and CXC chemokine
      receptors. Binding of vMIP-II, however, was not associated with the normal, rapid
      mobilization of calcium from intracellular stores; instead, it blocked calcium
      mobilization induced by endogenous chemokines. In freshly isolated human
      monocytes the virally encoded vMIP-II acted as a potent and efficient antagonist
      of chemotaxis induced by chemokines. Because vMIP-II could inhibit cell entry of
      human immunodeficiency virus (HIV) mediated through CCR3 and CCR5 as well as
      CXCR4, this protein may serve as a lead for development of broad-spectrum anti
      HIV agents.

PMID- 9287218
TI  - Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary
      adrenal responses to stress.
AB  - Variations in maternal care affect the development of individual differences in
      neuroendocrine responses to stress in rats. As adults, the offspring of mothers
      that exhibited more licking and grooming of pups during the first 10 days of life
      showed reduced plasma adrenocorticotropic hormone and corticosterone responses to
      acute stress, increased hippocampal glucocorticoid receptor messenger RNA
      expression, enhanced glucocorticoid feedback sensitivity, and decreased levels of
      hypothalamic corticotropin-releasing hormone messenger RNA. Each measure was
      significantly correlated with the frequency of maternal licking and grooming (all
      r's > -0.6). These findings suggest that maternal behavior serves to "program"
      hypothalamic-pituitary-adrenal responses to stress in the offspring.

PMID- 9287219
TI  - Structure of a murine leukemia virus receptor-binding glycoprotein at 2.0
      angstrom resolution.
AB  - An essential step in retrovirus infection is the binding of the virus to its
      receptor on a target cell. The structure of the receptor-binding domain of the
      envelope glycoprotein from Friend murine leukemia virus was determined to 2.0
      angstrom resolution by x-ray crystallography. The core of the domain is an
      antiparallel beta sandwich, with two interstrand loops forming a helical
      subdomain atop the sandwich. The residues in the helical region, but not in the
      beta sandwich, are highly variable among mammalian C-type retroviruses with
      distinct tropisms, indicating that the helical subdomain determines the receptor
      specificity of the virus.

PMID- 9287221
TI  - Regulation of human placental development by oxygen tension.
AB  - Cytotrophoblasts, specialized placental cells, proliferate early in pregnancy and
      then differentiate into tumor-like cells that establish blood flow to the
      placenta by invading the uterus and its vasculature. In this study,
      cytotrophoblasts cultured under hypoxic conditions (2 percent oxygen), mimicking
      the environment near the uterine surface before 10 weeks of gestation, continued
      proliferating and differentiated poorly. When cultured in 20 percent oxygen,
      mimicking the environment near uterine arterioles, the cells stopped
      proliferating and differentiated normally. Thus, oxygen tension determines
      whether cytotrophoblasts proliferate or invade, thereby regulating placental
      growth and cellular architecture.

PMID- 9287222
TI  - Proteolysis and DNA replication: the CDC34 requirement in the Xenopus egg cell
      cycle.
AB  - The cell division cycle gene, CDC34, is required for ubiquitin-mediated
      degradation of G1 regulators and cell cycle progression through the transition
      from G1 to S phase in budding yeast. A CDC34 requirement for S phase onset in
      higher eukaryotes has not been established. Studies of the simple embryonic cell
      cycle of Xenopus laevis eggs demonstrated that Cdc34p in a large molecular size
      complex was required in the initiation of DNA replication. Cdc34p appears to
      regulate the initiation function of Cdk2-cyclin E, perhaps through the
      degradation of the Xenopus cdk inhibitor, Xic1.

PMID- 9287223
TI  - X-ray structure of bacteriorhodopsin at 2.5 angstroms from microcrystals grown in
      lipidic cubic phases.
AB  - Lipidic cubic phases provide a continuous three-dimensional bilayer matrix that
      facilitates nucleation and growth of bacteriorhodopsin microcrystals. The
      crystals diffract x-rays isotropically to 2.0 angstroms. The structure of this
      light-driven proton pump was solved at a resolution of 2.5 angstroms by molecular
      replacement, using previous results from electron crystallographic studies as a
      model. The earlier structure was generally confirmed, but several differences
      were found, including loop conformations and side chain residues. Eight water
      molecules are now identified experimentally in the proton pathway. These findings
      reveal the constituents of the proton translocation pathway in the ground state.

PMID- 9287224
TI  - Cysteine and glutathione secretion in response to protein disulfide bond
      formation in the ER.
AB  - Protein folding in the endoplasmic reticulum (ER) often involves the formation of
      disulfide bonds. The oxidizing conditions required within this organelle were
      shown to be maintained through the release of small thiols, mainly cysteine and
      glutathione. Thiol secretion was stimulated when proteins rich in disulfide bonds
      were translocated into the ER, and secretion was prevented by the inhibition of
      protein synthesis. Endogenously generated cysteine and glutathione counteracted
      thiol-mediated retention in the ER and altered the extracellular redox. The
      secretion of thiols might link disulfide bond formation in the ER to intra- and
      intercellular redox signaling.

PMID- 9287225
TI  - Synaptic efficacy enhanced by glial cells in vitro.
AB  - In the developing nervous system, glial cells guide axons to their target areas,
      but it is unknown whether they help neurons to establish functional synaptic
      connections. The role of glial cells in synapse formation and function was
      studied in cultures of purified neurons from the rat central nervous system. In
      glia-free cultures, retinal ganglion cells formed synapses with normal
      ultrastructure but displayed little spontaneous synaptic activity and high
      failure rates in evoked synaptic transmission. In cocultures with neuroglia, the
      frequency and amplitude of spontaneous postsynaptic currents were potentiated by
      70-fold and 5-fold, respectively, and fewer transmission failures occurred. Glial
      cells increased the action potential-independent quantal release by 12-fold
      without affecting neuronal survival. Thus, developing neurons in culture form
      inefficient synapses that require glial signals to become fully functional.

PMID- 9287226
TI  - "Killer" impacts and life's origins.

PMID- 9287227
TI  - A controlled trial of two nucleoside analogues plus indinavir in persons with
      human immunodeficiency virus infection and CD4 cell counts of 200 per cubic
      millimeter or less. AIDS Clinical Trials Group 320 Study Team.
AB  - BACKGROUND: The efficacy and safety of adding a protease inhibitor to two
      nucleoside analogues to treat human immunodeficiency virus type 1 (HIV-1)
      infection are not clear. We compared treatment with the protease inhibitor
      indinavir in addition to zidovudine and lamivudine with treatment with the two
      nucleosides alone in HIV-infected adults previously treated with zidovudine.
      METHODS: A total of 1156 patients not previously treated with lamivudine or
      protease inhibitors were stratified according to CD4 cell count (50 or fewer vs.
      51 to 200 cells per cubic millimeter) and randomly assigned to one of two daily
      regimens: 600 mg of zidovudine (or stavudine) and 300 mg of lamivudine, or that
      regimen with 2400 mg of indinavir. The primary end point was the time to the
      development of the acquired immunodeficiency syndrome (AIDS) or death. RESULTS:
      The proportion of patients whose disease progressed to AIDS or death was lower
      with indinavir, zidovudine, and lamivudine (6 percent) than with zidovudine and
      lamivudine alone (11 percent; estimated hazard ratio, 0.50; 95 percent confidence
      interval, 0.33 to 0.76; P=0.001). Mortality in the two groups was 1.4 percent and
      3.1 percent, respectively (estimated hazard ratio, 0.43; 95 percent confidence
      interval, 0.19 to 0.99; P=0.04). The effects of treatment were similar in both
      CD4 cell strata. The responses of CD4 cells and plasma HIV-1 RNA paralleled the
      clinical results. CONCLUSIONS: Treatment with indinavir, zidovudine, and
      lamivudine as compared with zidovudine and lamivudine alone significantly slows
      the progression of HIV-1 disease in patients with 200 CD4 cells or fewer per
      cubic millimeter and prior exposure to zidovudine.

PMID- 9287228
TI  - Treatment with indinavir, zidovudine, and lamivudine in adults with human
      immunodeficiency virus infection and prior antiretroviral therapy.
AB  - BACKGROUND: The new protease inhibitors are potent inhibitors of the human
      immunodeficiency virus (HIV), and in combination with other antiretroviral drugs
      they may be able to cause profound and sustained suppression of HIV replication.
      METHODS: In this double-blind study, 97 HIV-infected patients who had received
      zidovudine treatment for at least 6 months and had 50 to 400 CD4 cells per cubic
      millimeter and at least 20,000 copies of HIV RNA per milliliter were randomly
      assigned to one of three treatments for up to 52 weeks: 800 mg of indinavir every
      eight hours; 200 mg of zidovudine every eight hours combined with 150 mg of
      lamivudine twice daily; or all three drugs. The patients were followed to monitor
      the occurrence of adverse events and changes in viral load and CD4 cell counts.
      RESULTS: The decrease in HIV RNA over the first 24 weeks was greater in the three
      drug group than in the other groups (P<0.001 for each comparison). RNA levels
      decreased to less than 500 copies per milliliter at week 24 in 28 of 31 patients
      in the three-drug group (90 percent), 12 of 28 patients in the indinavir group
      (43 percent), and none of 30 patients in the zidovudine-lamivudine group. The
      increase in CD4 cell counts over the first 24 weeks was greater in the two groups
      receiving indinavir than in the zidovudine-lamivudine group (P< or =0.01 for each
      comparison). The changes in the viral load and the CD4 cell count persisted for
      up to 52 weeks. All the regimens were generally well tolerated. CONCLUSIONS: In
      most HIV-infected patients with prior antiretroviral therapy, the combination of
      indinavir, zidovudine, and lamivudine reduces levels of HIV RNA to less than 500
      copies per milliliter for as long as one year.

PMID- 9287230
TI  - Mutation of RFXAP, a regulator of MHC class II genes, in primary MHC class II
      deficiency.
AB  - BACKGROUND: Major-histocompatibility-complex (MHC) class II deficiency is an
      autosomal recessive primary immunodeficiency disease in which MHC class II
      molecules are absent. It is a genetically heterogeneous disease of gene
      regulation resulting from defects in several transactivating genes that regulate
      the expression of MHC class II genes. The mutations responsible for MHC class II
      deficiency are classified according to complementation group (a group in which
      the phenotype remains uncorrected in pairwise fusions of cells). There are three
      known complementation groups (A, B, and C). METHODS: To elucidate the genetic
      defect in patients with MHC class II deficiency that was not classified
      genetically, we performed direct complementation assays with the three genes
      known to regulate the expression of MHC class II genes, CIITA, RFX5, and RFXAP,
      and the relevant mutations were identified in each patient. RESULTS: Mutations in
      the RFXAP gene were found in three patients from unrelated families, and the
      resulting defect was classified as belonging to a novel complementation group
      (D). Transfection with the wild-type RFXAP gene restored the expression of MHC
      class II molecules in the patients' cells. CONCLUSIONS: Mutations in a novel MHC
      class II transactivating factor, RFXAP, can cause MHC class II deficiency. These
      mutations abolish the expression of MHC class II genes and lead to the same
      clinical picture of immunodeficiency as in patients with mutations in the other
      two MHC class II regulatory genes.

PMID- 9287229
TI  - Stent placement compared with balloon angioplasty for obstructed coronary bypass
      grafts. Saphenous Vein De Novo Trial Investigators.
AB  - BACKGROUND: Treatment of stenosis in saphenous-vein grafts after coronary-artery
      bypass surgery is a difficult challenge. The purpose of this study was to compare
      the effects of stent placement with those of balloon angioplasty on clinical and
      angiographic outcomes in patients with obstructive disease of saphenous-vein
      grafts. METHODS: A total of 220 patients with new lesions in aortocoronary-venous
      bypass grafts were randomly assigned to placement of Palmaz-Schatz stents or
      standard balloon angioplasty. Coronary angiography was performed during the index
      procedure and six months later. RESULTS: As compared with the patients assigned
      to angioplasty, those assigned to stenting had a higher rate of procedural
      efficacy, defined as a reduction in stenosis to less than 50 percent of the
      vessel diameter without a major cardiac complication (92 percent vs. 69 percent,
      P<0.001), but they had more frequent hemorrhagic complications (17 percent vs. 5
      percent, P<0.01). Patients in the stent group had a larger mean (+/-SD) increase
      in luminal diameter immediately after the procedure (1.92+/-0.30 mm, as compared
      with 1.21+/-0.37 mm in the angioplasty group; P<0.001) and a greater mean net
      gain in luminal diameter at six months (0.85+/-0.96 vs. 0.54+/-0.91 mm, P=0.002).
      Restenosis occurred in 37 percent of the patients in the stent group and in 46
      percent of the patients in the angioplasty group (P=0.24). The outcome in terms
      of freedom from death, myocardial infarction, repeated bypass surgery, or
      revascularization of the target lesion was significantly better in the stent
      group (73 percent vs. 58 percent, P = 0.03). CONCLUSIONS: As compared with
      balloon angioplasty, stenting of selected venous bypass-graft lesions resulted in
      superior procedural outcomes, a larger gain in luminal diameter, and a reduction
      in major cardiac events. However, there was no significant benefit in the rate of
      angiographic restenosis, which was the primary end point of the study.

PMID- 9287231
TI  - Images in clinical medicine. HIV-associated nephropathy.

PMID- 9287233
TI  - Pathogenesis and treatment of sickle cell disease.

PMID- 9287232
TI  - The sleep of long-haul truck drivers.
AB  - BACKGROUND: Fatigue and sleep deprivation are important safety issues for long
      haul truck drivers. METHODS: We conducted round-the-clock electrophysiologic and
      performance monitoring of four groups of 20 male truck drivers who were carrying
      revenue-producing loads. We compared four driving schedules, two in the United
      States (five 10-hour trips of day driving beginning about the same time each day
      or of night driving beginning about 2 hours earlier each day) and two in Canada
      (four 13-hour trips of late-night-to-morning driving beginning at about the same
      time each evening or of afternoon-to-night driving beginning 1 hour later each
      day). RESULTS: Drivers averaged 5.18 hours in bed per. day and 4.78 hours of
      electrophysiologically verified sleep per day over the five-day study (range,
      3.83 hours of sleep for those on the steady 13-hour night schedule to 5.38 hours
      of sleep for those on the steady 10-hour day schedule). These values compared
      with a mean (+/-SD) self-reported ideal amount of sleep of 7.1+/-1 hours a day.
      For 35 drivers (44 percent), naps augmented the sleep obtained by an average of
      0.45+/-0.31 hour. No crashes or other vehicle mishaps occurred. Two drivers had
      undiagnosed sleep apnea, as detected by polysomnography. Two other drivers had
      one episode each of stage 1 sleep while driving, as detected by
      electroencephalography. Forty-five drivers (56 percent) had at least 1 six-minute
      interval of drowsiness while driving, as judged by analysis of video recordings
      of their faces; 1067 of the 1989 six-minute segments (54 percent) showing drowsy
      drivers involved just eight drivers. CONCLUSIONS: Long-haul truck drivers in this
      study obtained less sleep than is required for alertness on the job. The greatest
      vulnerability to sleep or sleep-like states is in the late night and early
      morning.

PMID- 9287234
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 28-1997. A 67-year-old woman with increasing neurologic deficits
      and a history of breast and ovarian cancer.

PMID- 9287235
TI  - Battling HIV on many fronts.

PMID- 9287236
TI  - The case of the bare lymphocyte syndrome--tracking down faulty transcription
      factors.

PMID- 9287237
TI  - The perils of drowsy driving.

PMID- 9287238
TI  - A novel approach to preventing insect-borne diseases.

PMID- 9287239
TI  - Abnormal activation of cytokine gene expression by intracisternal type A particle
      transposition: effects of mutations that result in autocrine growth stimulation
      and malignant transformation.
AB  - This review will focus on understanding the mechanisms resulting in the
      deregulated expression of cytokine genes that can lead to autocrine
      transformation. The murine genome contains over 2000 copies of intracisternal
      type A particles (IAPs), which under certain circumstances can transpose to
      different positions in the genome. When these transpositions affect the
      expression of a gene that can either positively or negatively regulate cell
      growth, a malignant or transformed cell may arise that has different growth
      characteristics than the parental cells. If this mutation confers a growth
      advantage to the cell, a tumor may develop. IAP transpositions have been
      frequently observed in hematopoietic cells, and they often affect cytokine gene
      expression. Genetic elements that possess similar transposable characteristics
      are also contained in the human genome. This review will discuss how IAP
      transpositions can result in the autocrine transformation of hematopoietic cells.

PMID- 9287240
TI  - Quantification of CD34+ cells mobilized into the peripheral blood predicts the
      yield of the leukapheresis product and can replace progenitor assays.
AB  - We reviewed 333 concomitant blood and cytapheresis samples from 101 patients with
      solid malignancies of various histological cell types. All samples were analyzed
      for CFU-GM, BFU-E and CD34+ determination. We found a good correlation between
      progenitor assays CFU-GM and CD34+ determination in the blood and cytapheresis (r
      = 0.77, p < 0.0001 and r = 0.79, p < 0.0001 respectively). The number of CD34+
      cells in the peripheral blood was predictive of the CD34+ yield in the
      cytapheresis (r = 0.86, p < 0.0001), and we determined that a threshold of 26
      CD34+/microliter of blood was sufficient to harvest 10(6) CD34+/kg in a single
      apheresis. Thirty breast cancer patients received injections of peripheral blood
      stem cells after the same high-dose chemotherapy. For these patients, we found a
      significant correlation between the quantity of CD34+ cells or CFU-GM collected
      and both granulocyte and platelet recovery. In conclusion, there is a very good
      correlation between CFU-GM assays and CD34+ determination and a good correlation
      between circulating CD34+ cells and the yield obtained by the cytapheresis. The
      number of CD34+ cells collected is also significantly correlated with
      hematological recovery. Because CD34+ quantification is an accurate, fast and
      inexpensive technique, this can lead to the progressive forsaking of progenitor
      assays in a clinical setting.

PMID- 9287241
TI  - Incidence of antibodies to interferon-beta in patients treated with recombinant
      human interferon-beta 1a from mammalian cells.
AB  - Patients receiving recombinant human interferon-beta 1a (IFN-beta 1a) produced in
      Chinese hamster ovary (CHO) cells were tested for the formation of neutralizing
      antibodies (NABs) to IFN-beta. Samples were tested in an enzyme-linked
      immunosorbent assay (ELISA), and if positive were then tested for neutralization
      of antiviral activity in an IFN-beta bioassay. A total of 793 patients with viral
      diseases, premalignant and malignant diseases, and multiple sclerosis received
      IFN-beta 1a in clinical studies. Long-term studies included 56 patients with
      cancer treated for 6 or 12 months and 334 patients with multiple sclerosis (MS)
      at the end of one year of treatment. All of the NAB-positive patients were found
      in the latter. Positivity in a single specimen was found in 14.4% of the MS
      patients. The incidence of sustained neutralizing antibody titres (i.e. positive
      in two tests at least 6 months apart) was 6.9% in this group. Comparison with
      results from other studies suggests that CHO-derived IFN-beta 1a induces less
      neutralizing antibody than IFN-beta 1b produced in E. coli.

PMID- 9287242
TI  - Quantification of IL-2 and IL-2 receptor mRNA in peripheral blood mononuclear
      cells by the RT-PCR based SHARP Signal system.
AB  - Nuclear transcription assays have shown that increases in interleukin 2 (IL-2)
      and its receptor (IL-2R) mRNA are reflected at the level of transcription.
      However, the quantification of transient and low-level expression of IL-2/IL-2R
      mRNAs in normal resting peripheral blood mononuclear cells (PBMC) requires a
      sensitive and reliable assay. We have established a quantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR) assay to measure IL-2/IL-2R
      transcripts by modifying the commercially-available SHARP Signal system to
      include IL-2/IL-2R RNA probes that were constructed by in vitro transcription of
      phagemid clones. To evaluate this modified SHARP Signal system and to demonstrate
      its clinical utility, the expression levels of IL-2 and IL-2R were assessed for
      40 healthy normal donors. The mean +/- SEM levels of transcripts in normal PBMC
      expressed in zeptomol per micrograms total RNA for IL-2, IL-2R alpha and IL-2R
      beta were 2.6 +/- 0.5, 23.3 +/- 2.2 and 157.2 +/- 32.2 respectively. Compared
      with the conventional RT-PCR and gel-electrophoresis-based detection method, the
      SHARP Signal system is fast, not labor-intensive and inexpensive, and can be
      readily adapted for the measurement of other cytokines or cytokine receptor gene
      expressions in a clinical diagnostic laboratory environment without extensive
      experience in molecular techniques.

PMID- 9287244
TI  - Differential modulation of LAK and ADCC functions of natural killer cells from AK
      5 tumor-bearing rats by IL-2, IL-12 and IFN-gamma.
AB  - Modulation of NK cell activity by various lymphokines is well documented. Freshly
      isolated NK cells exhibit natural cytotoxicity (NC) and antibody-dependent
      cellular cytotoxicity (ADCC) against certain targets. Upon stimulation with IL-2,
      the NK cells acquire lymphokine-activated killer (LAK) activity, which enables
      them to kill a wide variety of targets. Our results demonstrate that freshly
      isolated NK cells from tumor-bearing rats exhibit NK activity towards YAC-1, and
      ADCC activity towards AK-5 targets. Fresh NK cells did not lyse AK-5 targets in
      the absence of anti AK-5 antibody. However, in vitro culture of fresh NK cells in
      the presence of rat recombinant IL-2 (r-IL-2) over a period of 7 days resulted in
      complete loss of ADCC activity with concomitant acquisition of LAK activity on AK
      5 tumor targets. The LAK and ADCC activities could be effectively distinguished
      based on our observation that monoclonal anti-rat ICAM-1 and anti-rat LFA-1
      antibodies inhibited only LAK activity, but not ADCC activity, in addition, anti
      AK-5 antiserum, but not purified anti-AK-5 antibody, inhibited LAK activity,
      suggesting that soluble ICAM-1 present in hyperimmune serum could be responsible
      for inhibition of LAK activity. The loss of ADCC activity upon culture of NK
      cells with rIL-2 was not observed when the cultures were grown on a macrophage
      feeder layer. In addition, NK cells retained their ADCC activity when cultures
      were supplemented with a combination of recombinant IL-2 and IL-12. However IL-2,
      IFN-gamma or IL-12 alone did not prevent the loss of ADCC activity, suggesting
      the requirement of a combination of these lymphokines for the maintainance of
      ADCC activity.

PMID- 9287243
TI  - The effects of human macrophage inflammatory protein-1 alpha and its genetically
      modified variant, BB10010, on phagocyte function.
AB  - BB-10010 is a genetically modified form of human macrophage inflammatory protein
      1 alpha (MIP-1 alpha) with a single amino acid substitution of Asp26 by alanine,
      which inhibits aggregation of the native molecule. BB-10010 has stem cell
      protective properties, and has entered clinical trials for this purpose. The aim
      of this study was to determine the effects of BB-10010 on human phagocyte
      function and compare them with the native molecule. MIP-1 alpha and BB-10010 had
      identical dose-response curves in assays of calcium mobilization; however,
      neutrophils were less sensitive than monocytes to either MIP-1 alpha form,
      suggesting differences in receptor expression. Neither MIP-1 alpha type directly
      stimulated phagocyte superoxide production, nor did it have any priming effect on
      agonist-induced superoxide production. Both MIP-1 alpha and BB-10010 enhanced
      monocyte migration; however, cells were more sensitive to the native molecule,
      with optimal effects seen at 1 ng/ml compared with 100 ng/ml BB-10010.
      Concomitant alteration of CD11b, CD18, and CD49d (VLA-alpha 4) cell adhesion
      molecule expression was not seen with either MIP-1 alpha type. With the exception
      of the difference in monocyte sensitivity in chemotaxis assays, BB-10010
      reproduces the effects of the native molecule on phagocytes. BB-10010 does not
      have proinflammatory effects on neutrophil activation, and this bodes well for
      its clinical use.

PMID- 9287245
TI  - Control of transcriptional activation of the lipopolysaccharide binding protein
      (LBP) gene by proinflammatory cytokines.
AB  - The lipopolysaccharide binding protein (BLP) is of major importance for endotoxin
      recognition, presentation and subsequent cytokine induction in immune cells. As a
      member of a growing family of structurally and functionally related proteins, LBP
      is synthesized in hepatocytes and constitutively secreted into the bloodstream.
      During the acute-phase response, however, LBP levels rise substantially. In this
      article the mechanisms of induction of LBP protein synthesis are highlighted.
      Induction of LBP in hepatocytes is the result of transcriptional and
      posttranscriptional mechanisms, as shown by nuclear run-on and RNA half-life
      experiments. Cloning of the 5' flanking region of the LBP gene gave results
      consistent with the LBP promoter as a typical acute-phase protein promoter.
      Reporter-gene assays employing the Luciferase gene and mutation variants of the
      LBP promoter revealed that integrity of a common acute-phase promoter motif,
      binding STAT-3, is essential for activation of the LBP promoter. Elucidating the
      transcriptional activation mechanism could show the way how to therapeutically
      lower LBP levels in high-risk patients in order to reduce their susceptibility to
      Gram-negative septic shock.

PMID- 9287246
TI  - G-CSF activates STAT pathways in Kasumi-1 myeloid leukemic cells with the t(8;
      21) translocation: basis for potential therapeutic efficacy.
AB  - In an attempt to find new agents that promote differentiation and have
      therapeutic potential in acute myeloid leukemias, we have studied the effect of
      recombinant human granulocyte colony stimulating factor (rhG-CSF) on the Kasumi-1
      AML2 t(8; 21) cell line. Upon incubation with rhG-CSF (0.2-2000 ng/ml), Kasumi-1
      cells showed a peak of cell growth, with a subsequent decrease of cell survival
      after 4 days of culture. At that time, more than 80% of the cell population
      expressed myeloid differentiation antigens (CD11b, CD13, CD15 and CDw85), and
      increased G-CSF receptors. Gel shift assays were performed with nuclear extracts
      of Kasumi-1 cells after 1, 5, 10, 15, 30 and 60 min incubations with G-CSF and
      oligonucleotides containing the high-affinity SIF-binding site. At least three
      specific complexes were obtained, and shown by supershift assays to be
      STAT3/STAT3, STAT1/STAT3 and STAT1/STAT1 dimers. These results suggest that in G
      CSF-sensitive Kasumi-1 cells, normal JAK-STAT pathways are activated, providing a
      further molecular basis for the effect of G-CSF in these cells.

PMID- 9287247
TI  - Inclusion of IL-3 during retrovirally-mediated transduction on stromal support
      does not increase the extent of gene transfer into long-term engrafting human
      hematopoietic progenitors.
AB  - Interleukin 3 (IL-3) supports the survival of multilineage hematopoietic
      progenitors, and increases the extent of retrovirally mediated gene transfer into
      colony-forming cells. However, effects from the supraphysiological levels used in
      ex-vivo expansion and gene-therapy protocols on subsequent differentiation of
      human progenitors have not been well defined. In the current studies, the extents
      of retrovirally mediated transduction and lineage development from CD34+ cells
      cultured ex vivo in the presence or absence of IL-3 were compared. All
      transductions were performed in the presence of an irradiated stromal support
      layer, IL-6 and SCF, with and without inclusion of 10 ng/ml IL-3. Following
      transduction, colony-forming (CFU) assays were done, and the remaining cells were
      transplanted into cohorts of sibling beige/nude/xid (bnx) mice. Marrow from the
      mice was harvested 9-10 months post transplantation. The average extent of human
      CD45+ cell engraftment in the bone marrow and the human hematopoietic lineages
      recovered from the mice in the +IL-3 and -IL-3 groups did not vary significantly.
      No deleterious effects on the extent of engraftment, lineage generation, or
      survival of clonogenic progenitors was observed with inclusion of IL-3 in the
      transductions performed on stromal support. The percentage of G418-resistant
      human progenitors recovered from mice was equivalent. The extent of marking by
      the neo gene in the marrow of the mice was equal in both groups, and inverse PCR
      revealed that primitive cells transduced in the absence of IL-3 had generated
      progeny with slightly better clonal diversity than progenitors transduced in the
      presence of IL-3. These data show that, while transduction of colony-forming
      progenitors may not always be apparent, primitive human hematopoietic cells can
      be transduced to significant levels in the absence of IL-3.

PMID- 9287248
TI  - Multidrug resistance: molecular and clinical aspects.
AB  - Clinical drug resistance, a common and compromising side-effect during anticancer
      chemotherapy, is an acquired cellular resistance simultaneously to several
      cytotoxic drugs. Expression of the multidrug resistance gene (mdr) is one of the
      most-studied potential underlying mechanisms. The human mdr gene family
      encompasses two homologous members, the first of which, called the mdr1 gene, is
      the best-characterized so far. The human mdr1 gene has been shown to encode a
      membrane P-170 glycoprotein that, on the basis of its structure, is considered to
      act as a drug-efflux pump excreting various drugs from cells. The human mdr1 gene
      is thus a major regulated gene playing an important role in the molecular
      mechanism of multidrug resistance. Its bipartite structure of two similarly
      organized halves is explained by a gene fusion event during evolution. However,
      the clinical significance of this particular feature, if it seemed obvious in the
      1980s as a factor producing chemoresistance, is currently revised-being a marker
      of tumor aggressiveness rather than the cause of drug resistance.

PMID- 9287249
TI  - Mobilization of peripheral blood progenitor cells for allogeneic transplantation.
AB  - Allogeneic transplantation of peripheral blood stem/progenitor cells (PBSC/PBPC)
      has been increasingly used as an alternative to allogeneic bone marrow
      transplantation. To mobilize and collect a sufficient number of PBSC/PBPC for
      engraftment after allotransplantation, granulocyte colony-stimulating factor (G
      CSF) has been preferentially used. The mobilization protocol, however, has not
      been fully established. In this review, dose and schedule of G-CSF
      administration, characteristics of G-CSF-mobilized PBPC products, cytokines other
      than G-CSF for PBSC/PBPC mobilization, and safety of the PBSC/PBPC donors are
      discussed for clinical application of allogeneic PBSC/PBPC transplantation.

PMID- 9287251
TI  - DNA for genetic vaccination and therapy.
AB  - DNA coding for an antigen can be directly injected into muscle or skin and
      stimulate an immune response against the expressed antigen. The genes expressed
      can be derived from pathogens (e.g. viruses or bacteria), and can either code for
      surface molecules, which are often the basis for conventional peptide vaccines,
      or from the more genetically stable internal proteins. The DNA mimics a real
      infection in that the antigens are produced intracellularly where they are
      correctly folded and where they can be presented to the immune system so that
      cytotoxic T cells are stimulated as a defense mechanism. The DNA is expressed at
      low, but long-lasting, levels which is presumably the mechanism of its efficacy.
      Details of the mode of action and improvements for efficacy need to be worked
      out. Preclinical animal studies looked very promising, but need to be verified in
      humans. The method is safe and simple; DNA can be easily produced and
      transported, and can be composed of various genes. Recently also tumor-associated
      antigens have been tested in preclinical animal models, for example against colon
      cancer and malignant melanoma. Combinations with immune modulators are being
      worked out for improved efficacy. Successful therapies with this kind of gene
      medicine would be much cheaper and therefore superior to viral vectors. However,
      improvements are still required to prove that hopes are justified.

PMID- 9287250
TI  - MHC-derived peptides and the CD4+ T-cell repertoire: implications for autoimmune
      disease.
AB  - The receptor repertoire of peripheral CD4+ cells is primarily determined by
      selection processes in the thymus. These result in the positive selection of T
      cells whose receptors weakly recognize self-peptides restricted by class II self
      MHC heterodimers. A majority of such self-peptide partial agonists are likely to
      be derived from self-MHC molecules. It is suggested that these thymically
      selected, weakly autoreactive T cells may subsequently be stimulated by
      peripheral exposure to microbially derived agonists that 'mimic' corresponding
      self-MHC peptides. In turn, 'molecular mimicry' between microbial agonists and
      tissue-specific self-peptides may lead to T-cell-mediated autoimmune disease.
      Hence such disease may reflect 'three-way mimicry' between peptides of
      respectively target tissue, pathogen and self-MHC (or other self-peptide
      dominantly presented in the thymus). This hypothesis accounts for the role of MHC
      haplotype in determining susceptibility to (or protection from) autoimmune
      disease. Direct evidence is presented in favour of the model as applied to
      diseases such as rheumatoid arthritis, autoimmune uveitus and autoimmune
      diabetes. Strong circumstantial evidence, based primarily on sequence
      similarities, is also presented for other autoimmune diseases. However, it is
      noted that the statistics of database searches, and the lack of predictable
      correlation between sequence similarity and T-cell cross-reactivity, require that
      such evidence be substantiated by further direct experiment.

PMID- 9287252
TI  - The effects of alpha (10-Hz) and beta (22-Hz) "entrainment" stimulation on the
      alpha and beta EEG bands: individual differences are critical to prediction of
      effects.
AB  - Two different groups of normal college students were formed: One (the alpha
      group) received 10-Hz audiovisual (AV) stimulation for 8 minutes, and the other
      (beta) group received 22-Hz AV stimulation for 8 minutes. EEG power in the alpha
      (8-13 Hz) and beta (13-30 Hz) bands was FFT-extracted before, during, and for 24
      minutes after stimulation. It was found that baseline (prestimulation) alpha and
      beta power predict the effects of stimulation, leading to individual differences
      in responsivity. High-baseline alpha participants showed either no entrainment or
      relatively prolonged entrainment with alpha stimulation. Low-baseline
      participants showed transient entrainment. Baseline alpha also predicted the
      direction of change in alpha with beta stimulation. Baseline beta and alpha
      predicted beta band response to beta stimulation, which was transient enhancement
      in some participants, inhibition in others. Some participants showed relatively
      prolonged beta enhancement with beta stimulation.

PMID- 9287253
TI  - Change mechanisms associated with combined relaxation/EMG biofeedback training
      for chronic tension headache.
AB  - Therapeutic mechanisms hypothesized to underlie improvements in tension headache
      activity achieved with combined relaxation and electromyographic (EMG)
      biofeedback therapy were examined. These therapeutic mechanisms included (1)
      changes in EMG activity in frontal and trapezii muscles, (2) changes in central
      pain modulation as indexed by the duration of the second exteroceptive silent
      period (ES2), and (3) changes in headache locus of control and self-efficacy.
      Forty-four young adults with chronic tension-type headaches were assigned either
      to six sessions of relaxation and EMG biofeedback training (N = 30) or to an
      assessment only control group (N = 14) that required three assessment sessions.
      Measures of self-efficacy and locus of control were collected at pre- and
      posttreatment, and ES2 was evaluated at the beginning and end of the first,
      third, and last session. EMG was monitored before, during, and following training
      trials. Relaxation/EMG biofeedback training effectively reduced headache
      activity: 51.7% of subjects who received relaxation/biofeedback therapy recorded
      at least a 50% reduction in headache activity following treatment, while controls
      failed to improve on any measure. Improvements in headache activity in treated
      subjects were correlated with increases in self-efficacy induced by biofeedback
      training but not with changes in EMG activity or in ES2 durations. These results
      provide additional support for the hypothesis that cognitive changes underlie the
      effectiveness of relaxation and biofeedback therapies, at least in young adult
      tension-type headache sufferers.

PMID- 9287254
TI  - The effect of facial and trapezius muscle tension on respiratory impedance in
      asthma.
AB  - This study tested two theories about the relationship between voluntary changes
      in muscle tension and pulmonary function in asthma. Kotses has theorized that
      decreased facial muscle tension decreases respiratory impedance via a
      hypothesized vagaltrigeminal reflex, but that muscle tension in other muscle
      groups has no such effect. Others have suggested that decreased thoracic muscle
      tension improves pulmonary function. Subjects were 19 volunteer asthmatic adults.
      They performed 3-minute cycles of deliberate muscle contraction, alternating two
      each for the shoulder and forehead muscles, followed by dominant forearm
      contraction. Surface EMG was measured from the frontalis and right trapezius
      areas. Airway impedance was measured by forced oscillation pneumography. Cardiac
      interbeat interval and respiratory sinus arrhythmia were measured to assess vagal
      tone. Frequency dependence of respiratory impedance increased during shoulder
      tension, giving some support to the theory relating thoracic tension to
      impairment in pulmonary function. Correlational analyses suggested a negative
      relationship between changes in cardiac interbeat interval and both frontalis
      muscle tension and decreased compliance of tissues in the airways. These findings
      are the opposite of those predicted by the vagal-trigeminal reflex theory.

PMID- 9287255
TI  - Comparison of treatment outcome measures for irritable bowel syndrome.
AB  - We have examined the relations among three common treatment outcome measures in
      irritable bowel syndrome (IBS): end of treatment global ratings by a physician,
      end of treatment patient global ratings, and measures derived from a daily
      symptom diary completed by the patient. Eighty-four IBS patients (53 female, 31
      male) participated in a randomized controlled evaluation of three psychological
      treatment conditions for IBS. Treatment outcome measures from this trial
      (Blanchard et al., 1992) were used in the present methodological study. Physician
      global ratings were significantly correlated with patient global ratings (r =
      .45, p < .01). Both of these global ratings also correlated significantly with a
      composite score from patient diary ratings. Multiple regression analyses revealed
      that reductions in bloating and constipation account for 18% of the variance in
      patient global ratings. Global ratings at end of treatment by either patient or
      physician were only partially related to symptom relief as measured by a daily
      diary.

PMID- 9287256
TI  - Outcome of biofeedback-assisted relaxation for neurocardiogenic syncope and
      headache: a clinical replication series.
AB  - Preliminary evidence exists through single case reports that psychophysiological
      interventions may be useful in the treatment of syncope (fainting). To explore
      this possibility, a case series of ten patients with histories of recurrent
      unexplained syncope or near syncope, headache, and a poor response to or
      tolerance for medication was performed. All patients were treated with
      electromyographic, thermal, biofeedback as well as progressive and autogenic
      relaxation. Six of the ten patients showed a major decrease in symptoms at the
      end of treatment. Descriptive comparisons between the improved and unimproved
      group were made and a detailed case study of one improved patient is presented.
      The results suggested that biofeedback-assisted relaxation treatment was most
      effective in younger patients whose syncope was associated with a strong
      psychophysiological response and whose headaches were intermittent, not daily
      occurrences.

PMID- 9287257
TI  - Managing stable angina: time to re-evaluate medical therapy.

PMID- 9287258
TI  - European stroke prevention study 2: dipyridamole and acetylsalicylic acid in the
      secondary prevention of stroke.
AB  - In 1988, an optimal antiplatelet regimen for secondary stroke prevention remained
      to be defined. We undertook a randomised, placebo-controlled, double-blind trial
      to investigate the safely and efficacy of low-dose acetylsalicylic acid (ASA),
      modified-release dipyridamole, and the two agents in combination. Patients with
      prior stroke or transient ischaemic attack (TIA) were randomised to treatment
      with ASA alone (50 mg daily), modified-release dipyridamole alone (400 mg daily),
      the two agents in a combined formulation, or placebo. Primary endpoints were
      stroke, death, and stroke or death. TIA and other vascular events were secondary
      endpoints. Patients were followed on treatment for two years. We concluded that
      dipyridamole, in a modified-release form, at a dose of 200 mg b.d. and ASA 25 mg
      b.d., have been shown to be equally effective in the secondary prevention of
      ischaemic stroke and TIA; that when co-prescribed, the protective effects are
      additive, the combination being significantly more effective than each agent
      prescribed singly; and that low-dose ASA does not eliminate the propensity for
      induced bleeding.

PMID- 9287259
TI  - A randomised, double-blind, parallel-group comparison of venlafaxine and
      dothiepin in geriatric patients with major depression.
AB  - This randomised, double-blind study conducted at nine sites in the UK and the
      Netherlands compared the safety and antidepressant efficacy of venlafaxine and
      dothiepin. Ninety-two geriatric patients (aged 64-87 years) with major depression
      were randomly assigned to receive either venlafaxine or dothiepin for up to 43
      days. The dose of venlafaxine or dothiepin was titrated up to a maximum of 150 mg
      per day for the first 15 days, and thereafter could range from 50 to 150 mg per
      day. Adjusted mean scores on the MADRS and the HAM-D decreased significantly (p
      0.05) for baseline to the end of the study in both groups. A response to therapy
      was observed in 60% of patients in the venlafaxine group and 53% of patients in
      the dothiepin group on the MADRS, and in 60% of patients in both groups on the
      HAM-D. Suicidal ideation scores on the MADRS were significantly (p = 0.042) lower
      in the venlafaxine group at week 6. Treatment-emergent study events were the
      primary reasons for withdrawal in only 7% of venlafaxine-treated patients and 8%
      of dothiepin-treated patients. The results confirm the efficacy and tolerability
      of venlafaxine for treating major depression in the elderly.

PMID- 9287260
TI  - Helicobacter pylori eradication--comparison of three drug regimens and
      symptomatic assessment in duodenitis and antral gastritis.
AB  - Helicobacter pylori (Hp) eradication in peptic ulcer disease is associated with a
      greatly reduced recurrence rate. The optimal drug regimen for HP eradication
      remains uncertain. It is also unclear if eradication of Hp in duodenitis and
      antral gastritis improves symptoms. The aims of this study were to compare the
      efficacy of three drug regimens in the eradication of Hp and to assess if Hp
      eradication improved symptoms in patients with duodenitis and antral gastritis.
      Patients (n = 79) found to have duodenal ulcer, duodenitis and/or antral
      gastritis with a positive urease test (CLO) at endoscopy were allocated to one of
      the three regimens: A. omeprazole 20 mg b.d. and clarithromycin 500 mg t.d.s. for
      two weeks (n = 27), B. De-Nol 240 mg b.d. for four weeks, metronidazole 400 mg
      t.d.s. and amoxicillin 500 mg t.d.s. for one week (n = 26), and C. omeprazole 20
      mg b.d. and amoxicillin 500 mg t.d.s. for two weeks (n = 26). In conclusion,
      traditional 'triple' therapy with bismuth and two antibiotics achieved the
      highest Hp eradication rate and was best tolerated. Recolonisation with Hp was
      uncommon after eradication. Dyspeptic symptoms improved with Hp eradication in
      duodenitis and antral gastritis.

PMID- 9287261
TI  - Audit of oxygen therapy.
AB  - We audited the use of oxygen in our hospital. Over three days we found 119
      patients using oxygen, 21 wearing their mask incorrectly or not at all. The
      commonest indication was chronic obstructive pulmonary disease. Forty patients
      had no record of arterial gas analysis. Of those who had, 29 did not require
      oxygen and the average time from last arterial gas analysis was 5.7 days and only
      eight patients were being monitored with an oximeter. Taking into account the
      risk of exacerbating carbon dioxide retention and the problems that arise when
      discharging a patient who has been receiving oxygen therapy for the duration of
      their admission, we fee oxygen therapy should only be administered with the
      knowledge of the arterial gases and with frequent reassessment during therapy.

PMID- 9287262
TI  - Long-term potassium supplementation lowers blood pressure in elderly hypertensive
      subjects.
AB  - Following a randomised cross-over trial of the effect of a four-week 60 mmol/day
      potassium supplement versus placebo on blood pressure (BP), eight of the original
      18 hypertensive subjects continued with a 48 mmol daily potassium supplement for
      four months. For these eight subjects 24-h potassium excretion during placebo,
      one month of 60 mmol and four months of 48 mmol daily potassium supplementation
      phases was 56 +/- 23, 102 +/- 28 and 90 +/- 35 mmol/24 hours, respectively, and
      mean 24-h BP following each phase was 160 +/- 16/89 +/- 11, 147 +/- 13/83 +/- 12
      and 145 +/- 14/81+/- 9 mmHg respectively, a significant fall in mean 24-h SBP
      between four months of potassium supplement and placebo period of 15 +/- 13 mmHg
      (95% CI: 4, 26 mmHg, p = 0.02), although the fall in 24-h DBP was not significant
      (8 +/- 11 mmHg, 95% CI: 0, 17 mmHg, p = 0.08). Modest increases in dietary
      potassium intake could have significant effects on lowering BP in the large
      proportion of elderly subjects with hypertension.

PMID- 9287263
TI  - Acute admissions with heart failure to a district general hospital serving a
      multiracial population.
AB  - To assess te incidence, clinical characteristics and current strategies in the
      management of patients with acute heart failure, we conducted a prospective
      survey of all acute medical admissions with heart failure to a district hospital
      serving a city centre population of 300,000 people in a multiracial community. Of
      7451 such admissions, 348 (4.7%) were diagnosed as having acute heart failure:
      265 Caucasian (76.1%), 27 black/Afro Caribbean (7.7%), 56 Indo-Asian (16.1%).
      Complete clinical data were available from 260 patients. The main presenting
      symptom was dyspnoea in 233 patients (89.6%) and chest pain in 60 patients
      (23.1%); 139 patients (53.5%) had a history of ischaemic heart disease, 87
      (33.5%) hypertension and 49 (18.8%) had diabetes; 103 patients (39.6%) had a
      previous history of heart failure; 75 patients (28.8%) were in atrial
      fibrillation. An echocardiogram was performed in 89 patients (34.2%). On
      admission, ACE inhibition was prescribed to only 78 patients (30.0). The
      diagnosis of heart failure was stated on the hospital inpatient data sheet (KMR
      1) in only 170 patients (65.4%). Following admission, 50 patients (19.2%) died
      while in the wards. Heart failure is a common problem among acute medical
      admissions and has a poor prognosis. The KMR-1 diagnosis may underestimate the
      prevalence of heart failure.

PMID- 9287264
TI  - Audit of once-daily dosing gentamicin therapy in neutropenic fever.
AB  - During a 12-month study, 42 adult patients with febrile neutropenia (granulocytes
      < 1 x 10(9)/l) were treated with once-daily gentamicin (5 mg/kg). Serum
      gentamicin trough levels were measured 24 hours after the first dose, then twice
      weekly if < 1 mg/l. Gentamicin was halved if the trough level was 1-2 mg/l and
      usually stopped if > 2 mg/l. One hundred and sixty samples were assayed: 122
      (76%) < 1 mg/l, 27 (17%) l-2 mg/l and 11 (7%) > 2 mg/l. All 1-2 mg/l samples and
      three of the > 2 mg/l samples (taken at the wrong time) reverted to <1 mg/l with
      dosage adjustment. The protocol proved simple and effective with a low incidence
      of gentamicin-associated nephrotoxicity (7%) and no sepsis-related deaths.

PMID- 9287265
TI  - Immune modulation and sepsis.
AB  - The pathogenesis of sepsis involves not only microbial toxins but also activated
      host inflammatory mediators. Therefore, besides conventional antibiotic or
      surgical treatment of infection and supportive intensive therapy, modulating host
      inflammatory mediators as a conjunctive therapeutic option has been explored in
      the past decade. Although successful in animal models of sepsis, inhibiting host
      inflammatory response in human sepsis has failed to improve survival or otherwise
      show efficacy. Studies are needed which better describe the circumstances under
      which these therapies may ultimately prove successful.

PMID- 9287266
TI  - Controversy and consensus in the management of upper gastrointestinal disease in
      primary care. The International Gastro Primary Care Group.
AB  - Approximately 5% of all primary care consultations in the UK are for upper
      gastrointestinal (GI) diseases, the most common of which is dyspepsia, with a
      prevalence of between 25 and 50% in the western world. The exact definition of
      dyspepsia is elusive, which has resulted in confusion about diagnosis and
      treatment, highlighting the need for management guidelines. The International
      Gastro Primary Care Groups (IGPCG) has developed, by consensus, practical
      guidelines to help GPs manage patients with upper GI symptoms. After a detailed
      history is taken, alarm symptoms identified and organic disease excluded, the
      predominant symptom should be identified. This strategy, as outlined in the IGPCG
      upper GI disease management plan, can help the GP in the selection of the most
      appropriate treatment for each patient. This plan is flexible enough to be used
      in a wide variety of healthcare systems and will evolve as new evidence becomes
      available.

PMID- 9287267
TI  - On the causes of collapse and sudden death by Avicenna.
AB  - Avicenna's views on the causes of collapse and sudden death are presented from a
      literal translation of the mediaeval Arabic text. Medical knowledge based on
      observation mixed with pure abstract reasoning forms the essence of Avicenna's
      medical writings.

PMID- 9287269
TI  - Spontaneous regression of cancer or misdiagnosis? Four case reports.
AB  - Four case reports regarding possible spontaneous regression of cancer are given.
      This is a rare but previously documented occurrence, with the literature
      suggesting possible causal factors for cancer regression or an indefinite period
      of dormancy. These include genetic, hormonal, immunological and psychological
      factors. However, the literature makes no reference to potential misdiagnosis,
      either clinically or histologically. The effect of being diagnosed as having
      terminal cancer is profound and even after regression or resolution of the
      disease, there are inevitable psychological sequelae.

PMID- 9287268
TI  - Koch's or Crohn's?
AB  - Abdominal tuberculosis is not uncommon in the UK, especially in Asian immigrants.
      It resembles Crohn's disease clinically and radiologically, and it may be
      difficult to differentiate between them, even at laparotomy or histology. The
      distinction is important, however, for proper management of the two conditions.
      Every effort must be made to exclude abdominal tuberculosis before the patient is
      diagnosed as having Crohn's disease and is treated with steroids.

PMID- 9287270
TI  - Henoch-Schonlein purpura associated with ranitidine.
AB  - Ranitidine is one of the widely prescribed H2 receptor antagonists in the
      treatment of peptic ulcer. It is well tolerated and has few side-effects.
      Vasculitic rash occurring in association with ranitidine has been described. We
      report a case of a 39-year-old man who developed a purpuric rash, polyarthritis,
      abdominal pain, melaena and impaired renal function characteristic of Henoch
      Schonlein purpura, following treatment with ranitidine.

PMID- 9287271
TI  - Slipping rib syndrome: an overlooked cause of chest and abdominal pain.
AB  - Slipping rib syndrome is a poorly recognised cause of chest and abdominal pain.
      It occurs principally in the middle-aged but may occur at any age. It is equally
      common in men and women and is frequently confused with other serious causes of
      chest and abdominal pain. Patients are often subjected to extensive and sometimes
      invasive needless investigation for unexplained symptoms. Greater awareness of
      this syndrome among clinicians could sale both patient and doctor time and
      unnecessary concern. Two case reports are presented.

PMID- 9287272
TI  - Subdural effusion in chronic cryptococcal meningitis in a cirrhotic patient.

PMID- 9287273
TI  - Widening of the mediastinum following a sternal fracture.
AB  - Sternal fractures, once thought of as uncommon, occur with increasing frequency,
      parallelling the incidence of motor vehicle accidents. A fractured sternum can
      produce a widening of the mediastinum even in the absence of an aortic injury.
      The Advanced Trauma Life Support course teaches that a widening of the
      mediastinum after blunt chest injury is an indication for aortography. In this
      case report we recommend computerised axial tomography (CT) scan of the chest as
      the investigation of choice in the non-hypotensive patient who has sustained a
      fractured sternum after a blunt chest trauma, and who has widening of the
      mediastinum on the chest X-ray, with no other radiological features suggesting
      traumatic aortic rupture.

PMID- 9287275
TI  - A case of relapsing psittacosis associated with a stroke.
AB  - Psittacosis, caused by Chlamydia psittaci, is mainly associated with an atypical
      pneumonia. We report a case of psittacosis where onset of respiratory symptoms
      was soon followed by the onset of focal neurological signs, a very uncommon
      feature. Despite adequate treatment with erythromycin, the patient relapsed when
      re-exposed to a sick pet bird. A prolonged course of doxycycline led to
      resolution of the pneumonia, but it is important to recall that successful
      management must also include the elimination of the precipitating cause of the
      infection.

PMID- 9287274
TI  - Ruptured hepatoma presenting with peritonitis and acute lactic acidosis.
AB  - A case is reported in which a large hepatoma presented with rupture and acute
      severe lactic acidosis. Spontaneous rupture is a rare but recognised mode of
      presentation of hepatoma. Malignancy has also occasionally been associated with
      acute lactic acidosis, though the association with hepatoma has not previously
      been reported.

PMID- 9287276
TI  - Acute renal failure in association with fusidic acid.

PMID- 9287277
TI  - Functional correlates in the rehabilitation of occupational low back pain.
AB  - The aim of this preliminary report was to identify physiological parameters
      related to functional improvement in industrial workers with occupational low
      back pain (LBP) undergoing an intensive rehabilitation program. Four able-bodied
      and four LBP industrial workers were evaluated before and after a 4-week
      rehabilitation program. Dynamic and static strength tests, namely sustained
      isometric contractions, were performed in conjunction with surface
      electromyographic (EMG) measurements. Significant pre-rehabilitation differences
      were found between the two groups. Measured forces changed significantly in LBP
      subjects immediately after rehabilitation. No significative changes were found in
      the control subjects after the rehabilitation program. After rehabilitation, the
      slope of decay of the median frequency of the EMG power spectrum at L4 level,
      during a 60-sec isometric submaximal (60% MVC) contraction, decreased
      significantly (p < 0.02) indicating a lower fatigue level.

PMID- 9287278
TI  - Instrumental and metabolic evaluation of patients affected by peripheral arterial
      occlusive disease (PAOD) following surgical revascularization surgery.
AB  - Experiments were performed on eight subjects affected by peripheral arterial
      occlusive disease (PAOD) of the lower limbs. Each patient was submitted to
      Ecodoppler, angiography and the "Treadmill test". Two bioptic muscle of these
      patients. A sample was used for the spectrophotometric and
      spectrophotofluorimetric determinations of: glycogen, pyruvate, lactate, citrate,
      alpha-ketoglutarate, malate, aspartate, glutamate, AMP, ADP, ATP and creatine
      phosphate (CP). The other bioptic sample was used to determine the following
      enzyme activities: hexokinase, phosphofructokinase, pyruvate kinase, lactate
      dehydrogenase, citrate synthase, succinate dehydrogenase, malate dehydrogenase,
      total NADH cytochrome c reductase, cytochrome oxidase, aspartate aminotransferase
      and alanine aminotransferase. Patients showed an increase in lactate
      dehydrogenase, total NADH cytochrome c reductase and succinate dehydrogenase
      activities, a decrease in glycogen, ATP and CP concentrations. Telethermographic
      data showed patient muscle thermic emission quantitatively different from control
      group. The telethermographic test can be used as an additional diagnostic tool to
      determine and monitor the efficiency of a muscle undergoing metabolic failure.

PMID- 9287280
TI  - [Clinical research in nursing care].

PMID- 9287281
TI  - [Speech implants following total laryngectomy and nursing care].

PMID- 9287279
TI  - Individual susceptibility to inhaled pollutants--identification, mechanisms and
      public health policy implications.
AB  - In every community, there are individuals whose chances of illness or accident
      are greater than those of others. In susceptible persons, adverse health effects
      occur at a lower exposure than in the majority of population. The reason for
      this, though often weak, can usually be ascertained. The paper focuses primarily
      on host factors that may increase an individual's susceptibility to air
      pollutants present in the general environment. These factors include genetic
      background, age, gender, nutritional status, physiological status, presence of
      coexisting lung disease, and lifestyle. They relate to various mechanisms of
      individual susceptibility to air pollutants from the environment into the body,
      to alterations in detoxification and immunological reactions, and to variations
      in the responsiveness of lung tissues. Several epidemiological techniques to
      detect biological events relevant to host susceptibility and disease progression
      are mentioned. They are mainly based on genetic traits, host characteristics,
      pulmonary function tests, biochemical and immune changes. Measuring the
      variations in risk among susceptible individuals is necessary to assess correctly
      respiratory health risk due to inhaled pollutants at the population level, and
      subsequently to develop rational public health policy to reduce the incidence of
      those diseases in a given population. Before being able to formulate this policy,
      however, one must know how to detect those individuals who are susceptible to air
      pollutants.

PMID- 9287282
TI  - [Admission of patients with sickle cell disease in pain crisis].

PMID- 9287283
TI  - [Monitoring the end of pregnancy].

PMID- 9287284
TI  - [Pain evaluation and therapeutic management in the recovery room].

PMID- 9287285
TI  - [Clinical research: definition and principles].

PMID- 9287286
TI  - [Experience of an infarction, which changes?].

PMID- 9287287
TI  - [Colostomy: in search of the unknown].

PMID- 9287288
TI  - [Anxieties and fears in diabetic patients].

PMID- 9287289
TI  - [Introduction to the nursing diagnosis of pain, a team undertaking (comparative
      analysis of 2 methods of change)].

PMID- 9287290
TI  - Lipoprotein trafficking in vascular cells. Molecular Trojan horses and cellular
      saboteurs.
AB  - During the pathogenesis of atherosclerosis, inflammatory cells such as the
      monocyte-derived macrophage accumulate in the vessel wall where they release
      cytokines. Initially, cytokines may assist in CE removal of lipoprotein-derived
      cholesterol/CE hydrolysis to clear intracellular lipid. When plasma levels of LDL
      become elevated, the vessel wall becomes lipid-engorged over time because it is
      unable to traffick the large amounts of endocytosed LDL-CE from the cell. In
      addition, lipoprotein entrapment by the extracellular matrix can lead to the
      progressive oxidation of LDL because of the action of lipoxygenases, reactive
      oxygen species, peroxynitrite, and/or myeloperoxidase. A range of oxidized LDL
      species is thus generated, ultimately resulting in their delivery to vascular
      cells through several families of scavenger receptors (Fig 1). These molecular
      Trojan horses and cellular saboteurs once formed or deposited in the cell can
      contribute to, and participate in, formation of macrophage- and smooth muscle
      derived foam cells. A lipid-enriched fatty streak along the vessel wall can
      ensue. In addition to foam cell development, products of LDL peroxidation may
      activate endothelial cells, increase smooth muscle mitogenesis, or induce
      apoptosis because of the effects of oxysterols and products of lipid peroxidation
      (Fig 1). Because antioxidant defenses may be limited in the microenvironment of
      the cell or within LDL, the oxidation process continues to progress. Enzymes
      associated with HDL such as PAF acetylhydrolase and paraoxonase can participate
      in the elimination of biologically active lipids, but diminished cellular
      antioxidant activity coupled with low levels of HDL may allow acceleration of the
      clinical course of vascular disease. There is still much to be learned about how
      modified LDL initiate cellular signals that lead to inflammation, mitosis, or
      cholesterol accumulation. The present challenges include elucidation of the key
      signaling events that regulate lipoprotein-derived cholesterol trafficking in the
      vessel wall, which can impact on the pathogenesis of vascular disease.

PMID- 9287291
TI  - A novel Go-mediated phototransduction cascade in scallop visual cells.
AB  - Scallop retinas contain ciliary photoreceptor cells that respond to light by
      hyperpolarization like vertebrate rods and cones, but the response is generated
      by a different phototransduction cascade from those of rods and cones. To
      elucidate the cascade, we investigated a visual pigment and a G-protein
      functioning in the hyperpolarizing cell. Sequencing of cDNAs and in situ
      hybridization experiments showed that the hyperpolarizing cells express a novel
      subtype of visual pigment, which showed significant differences in amino acid
      sequence from other visual pigments. Cloning cDNA genes of G-protein and
      immunohistochemical analysis revealed the presence of an alpha subunit of a Go
      type G-protein, 83% identical in amino acid sequence to mammalian Go(alpha) in
      the nervous system, in the photoreceptive region of the cells. The results
      demonstrate that a novel, Go-mediated, phototransduction cascade is present in
      the hyperpolarizing cells. The phototransduction cascade in the scallop
      hyperpolarizing cell provides an alternative system to investigate Go-mediated
      transduction pathways in the nervous system. Molecular phylogenetic analysis
      strongly suggests that the Go-mediated phototransduction system emerged before
      the divergence of animals into vertebrate and invertebrate in the course of
      evolution.

PMID- 9287292
TI  - MgADP antagonism to Mg2+-independent ATP binding of the sulfonylurea receptor
      SUR1.
AB  - Pancreatic beta-cell ATP-sensitive potassium (KATP) channels play an important
      role in the regulation of glucose-induced insulin secretion. The beta-cell KATP
      channel comprises two subunits, the sulfonylurea receptor SUR1, a member of the
      ATP-binding cassette (ABC) superfamily, and Kir6.2, a member of the inward
      rectifier K+ channel family. The activity of the KATP channel is under complex
      regulation by the intracellular ATP and ADP. To understand the roles of the two
      nucleotide-binding folds (NBFs) of SUR1 in the regulation of KATP channel
      activity, we introduced point mutations into the core consensus sequence of the
      Walker A or B motif of each NBF of SUR1 and characterized ATP binding and ADP or
      MgADP antagonism to it. SUR1 was efficiently photolabeled with 8-azido-[alpha
      32P]ATP and 8-azido-[gamma-32P]ATP in the presence or absence of Mg2+ or
      vanadate. NBF1 mutations impaired ATP binding, but NBF2 mutations did not. MgADP
      strongly antagonized ATP binding, and the NBF2 mutation reduced MgADP antagonism.
      These results show that SUR1, unlike other ABC proteins, strongly binds ATP at
      NBF1 even in the absence of Mg2+ and that MgADP, through binding at NBF2,
      antagonizes the Mg2+-independent high affinity ATP binding at NBF1.

PMID- 9287293
TI  - Acceleration of amyloid fibril formation by specific binding of Abeta-(1-40)
      peptide to ganglioside-containing membrane vesicles.
AB  - The interaction of Alzheimer's Abeta peptide and its fluorescent analogue with
      membrane vesicles was studied by spectrofluorometry, Congo Red binding, and
      electron microscopy. The peptide binds selectively to the membranes containing
      gangliosides with a binding affinity ranging from 10(-6) to 10(-7) M depending on
      the type of ganglioside sugar moiety. This interaction appears to be ganglioside
      specific as under our experimental conditions (neutral pH, physiologically
      relevant ionic strength), no Abeta binding was observed to ganglioside-free
      membranes containing zwitterionic or acidic phospholipids. Importantly, the
      addition of ganglioside-containing vesicles to the peptide solution dramatically
      accelerates the rate of fibril formation as compared with that of the peptide
      alone. The present results strongly suggest that the membrane-bound form of the
      peptide may act as a specific "template" (seed) that catalyzes the
      fibrillogenesis process in vivo.

PMID- 9287294
TI  - DNA damage recognition by XPA protein promotes efficient recruitment of
      transcription factor II H.
AB  - The human basal transcription factor IIH (TFIIH) is an essential component of the
      nucleotide excision repair machinery. TFIIH is required for reaction steps
      concomitant with or prior to the formation of dual incisions in the damaged DNA
      strand. To understand the mechanism underlying the recruitment of TFIIH to DNA
      damage sites we have analyzed i) the direct affinity of TFIIH for damaged or
      undamaged DNA and ii) the interaction of TFIIH with XPA.DNA complexes, formed
      using unirradiated or UV-irradiated DNA. Filter binding assays showed that TFIIH
      has some affinity for the DNA, but in contrast to XPA, does not show any
      preference for UV-irradiated DNA. Pull-down experiments demonstrated that TFIIH
      binds to XPA.DNA complexes in an UV damage-dependent manner by a direct protein
      protein interaction with XPA. We propose that an enhancement of the affinity of
      XPA protein for TFIIH could arise from conformational changes of XPA when it
      binds to UV lesions on the DNA.

PMID- 9287296
TI  - Molecular basis for the interaction of [Nle4,D-Phe7]melanocyte stimulating
      hormone with the human melanocortin-1 receptor.
AB  - The melanocortin-1 receptor (MC1R) is a seven-transmembrane (TM) G-protein
      coupled receptor whose natural ligands are the melanocortin peptides,
      adrenocorticotropic hormone, and alpha-, beta-, and gamma- melanocyte stimulating
      hormone (MSH). To test a previously constructed three-dimensional model of the
      molecular interaction between the long-acting, superpotent alpha-MSH analog
      [Nle4,D-Phe7]MSH (NDP-MSH) and the human MC1R we examined the effects of site
      directed receptor mutagenesis on the binding affinity and potency of NDP-MSH. In
      addition, we also examined the effects of these same mutations on the binding
      affinity and potency of the structurally related agonists alpha-MSH, gamma-MSH,
      and Ac-Nle4-cyclic-[Asp5,His6,D-Phe7,Arg8,Trp9,Lys10]NH2 (MT-II). Mutagenesis of
      acidic receptor residues Glu94 in TM2 and Asp117 or Asp121 in TM3 significantly
      altered the binding affinity and potency of all four agonists suggesting that
      these receptor residues are important to the ligand-receptor interactions of all.
      A disproportionate change in agonist potency versus affinity observed with
      simultaneous mutation of these acidic residues (mutant constructs D117A/D121A or
      E94A/D117A/D121A) or introduction of a single positive charge (mutant construct
      D121K) also implicates these residues in receptor activation. In addition,
      results from the individual mutation of aromatic receptor residues Phe175,
      Phe196, and Phe257, and simultaneous mutation of multiple TM4, -5, and -6
      tyrosine and phenylalanine residues suggests that aromatic-aromatic ligand
      receptor interactions also participate in binding these melanocortins to the
      MC1R. These experiments appear to have identified some of the critical receptor
      residues involved in the ligand-receptor interactions between these melanocortins
      and the hMC1R.

PMID- 9287295
TI  - A conditionally expressed third partner stabilizes or prevents the formation of a
      transcriptional activator in a three-hybrid system.
AB  - We describe a three-hybrid system that involves three polypeptides that allow or
      prevent the formation of the transcriptional activator. Beside the two-hybrid
      fusion proteins, the third partner is under the control of the Met25 promoter,
      which is positively regulated in medium lacking methionine. We document a
      situation where such a third partner promotes interaction between two proteins,
      one fused to a DNA-binding domain and the other fused to an activator domain.
      This is demonstrated for cdk7-MAT1 interaction stabilized by the presence of
      cyclin H; these three polypeptides are found either free or associated with the
      transcription/DNA repair factor TFIIH. We also document the capacity of our
      system to conditionally inhibit the interaction between two polypeptides that
      otherwise elicit a positive two-hybrid response. This is demonstrated for Ras-Raf
      interaction precluded by an excess of Raf. The presence of a methionine-regulated
      promoter provides an "on" or "off" switch for the formation of the
      transcriptional activator, thus also providing an excellent control to evaluate
      the activation or inhibition properties of the third partner.

PMID- 9287297
TI  - Thermal conversion from low- to high-activity forms of catalase I from Bacillus
      stearothermophilus.
AB  - Catalase I from Bacillus stearothermophilus has the interesting property of
      increasing its enzyme activity on heating. It was confirmed that after heating at
      70 degrees C for 10 min or 65 degrees C for 20 min, almost all the enzyme
      molecules were converted irreversibly to the activated form. The increase in kcat
      from 1400 to 3930 s-1 and the decrease in Km for H2O2 from 4.4 to 2.7 mM by heat
      activation indicate changes in the kinetic property of the enzyme molecule.
      Therefore, it follows that catalase I has two active forms, a high-activity form
      and a low-activity form. The heat activation process followed the first-order
      kinetics with an activation enthalpy (DeltaH*) of 191 kJ/mol while the heat
      denaturation process had a DeltaH* of 545 kJ/mol. The CD spectra of the two
      enzyme forms had small but marked differences. The conversion of the low-activity
      form to the high-activity form was an endothermic process with a Tm of 56 degrees
      C, which is much lower than that of the heat denaturation (Tm = 76 degrees C),
      and the enthalpy change for the transition was only 5% of that for the
      denaturation. It has to be noted that the high-activity form of the enzyme was
      converted back to a low-activity form through the process of denaturation,
      refolding, and reconstitution with heme. In addition, the newly obtained low
      activity form was brought to a high-activity form by heating. These results
      suggest that the native state of catalase I has two active conformations that are
      roughly the same but not identical and are separated by a high energy barrier.

PMID- 9287298
TI  - Threonine 435 of Escherichia coli DnaA protein confers sequence-specific DNA
      binding activity.
AB  - The Escherichia coli DnaA protein, as a sequence-specific DNA binding protein,
      promotes the initiation of chromosomal replication by binding to four asymmetric
      9-mer sequences termed DnaA boxes in oriC. Characterization of N-terminal, C
      terminal, and internal in-frame deletion mutants identified residues near the C
      terminus of DnaA protein required for DNA binding. Furthermore, genetic and
      biochemical characterization of 11 missense mutations mapping within the C
      terminal 89 residues indicated that they were defective in DNA binding. Detailed
      biochemical characterization of one mutant protein bearing a threonine to
      methionine substitution at position 435 (T435M) revealed that it retained only
      nonspecific DNA binding activity, suggesting that threonine 435 imparts
      specificity in binding. Finally, T435M was inactive on its own for in vitro
      replication of an oriC plasmid but was able to augment limiting levels of wild
      type DnaA protein, consistent with the proposal that not all of the DnaA monomers
      in the initial complex are bound specifically to oriC and that direct interaction
      occurs among monomers.

PMID- 9287299
TI  - Rapid Up-regulation of IkappaBbeta and abrogation of NF-kappaB activity in
      peritoneal macrophages stimulated with lipopolysaccharide.
AB  - Lipopolysaccharide (LPS) administration to mice elicited the activation of
      nuclear factor kappaB (NF-kappaB) in several tissues including liver and
      macrophages. Maximal activation was observed 1 h after treatment but declined at
      3 and 6 h. The levels of IkappaBalpha and IkappaBbeta were analyzed during this
      period in an attempt to correlate NF-kappaB activity with IkappaB resynthesis.
      Degradation of IkappaBalpha was very rapid and was followed by recovery 1 h after
      LPS administration. IkappaBbeta degradation, which has been associated with
      persistent NF-kappaB activation, was complete at 1 h. However, a rapid recovery
      of IkappaBbeta in these tissues was observed at 3 h in parallel with the
      abrogation of NF-kappaB activity. Immunolocalization of newly synthesized
      IkappaBbeta by confocal microscopy revealed its preferential accumulation in the
      cytosol. Analysis of IkappaBbeta by Western blot using high resolution
      polyacrylamide gel electrophoresis showed the presence of two bands in cytosolic
      extracts of LPS-treated macrophages at 3 h, but only one band with the same
      mobility as the control was detected at 6 h. Moreover, treatment of extracts of
      resynthesized IkappaBbeta with alkaline phosphatase resulted in the accumulation
      of the protein of slightly higher electrophoretic mobility, indicating the
      prevalence of a rapid phosphorylation of the newly synthesized IkappaBbeta. At
      the mRNA level, up-regulation of IkappaBbeta was observed in macrophages
      stimulated for 1 h with LPS. When the effect of pro-inflammatory cytokines was
      investigated, tumor necrosis factor alpha, but not interleukin-1 or interferon
      gamma, promoted an important degradation of IkappaBbeta followed by an increase
      in the mRNA at 1 h. These results suggest the existence of LPS- and tumor
      necrosis factor alpha- specific pathways involved in a rapid IkappaBbeta
      degradation and resynthesis and might explain the transient period of activation
      of NF-kappaB in these tissues upon stimulation with these factors. This rapid
      control of NF-kappaB function may contribute to the attenuation of the
      inflammatory response of these cells.

PMID- 9287300
TI  - Characterization of alpha-ketoglutarate-dependent taurine dioxygenase from
      Escherichia coli.
AB  - The Escherichia coli tauD gene is required for the utilization of taurine (2
      aminoethanesulfonic acid) as a sulfur source and is expressed only under
      conditions of sulfate starvation. The sequence relatedness of the TauD protein to
      the alpha-ketoglutarate-dependent 2,4-dichlorophenoxyacetate dioxygenase of
      Alcaligenes eutrophus suggested that TauD is an alpha-ketoglutarate-dependent
      dioxygenase catalyzing the oxygenolytic release of sulfite from taurine (van der
      Ploeg, J. R., Weiss, M. A., Saller, E., Nashimoto, H., Saito, N., Kertesz, M. A.,
      and Leisinger, T. (1996) J. Bacteriol. 178, 5438-5446). TauD was overexpressed in
      E. coli to approximately 70% of the total soluble protein and purified to
      apparent homogeneity by a simple two-step procedure. The apparent Mr of 81,000 of
      the native protein and the subunit Mr of 37,400 were consistent with a
      homodimeric structure. The pure enzyme converted taurine to sulfite and
      aminoacetaldehyde, which was identified by high pressure liquid chromatography
      after enzymatic conversion to ethanolamine. The reaction also consumed equimolar
      amounts of oxygen and alpha-ketoglutarate; ferrous iron was absolutely required
      for activity; and ascorbate stimulated the reaction. The properties and amino
      acid sequence of this enzyme thus define it as a new member of the alpha
      ketoglutarate-dependent dioxygenase family. The pure enzyme showed maximal
      activity at pH 6.9 and retained activity on storage at -20 degrees C for several
      weeks. Taurine (Km = 55 microM) was the preferred substrate, but pentanesulfonic
      acid, 3-(N-morpholino)propanesulfonic acid, and 1,3-dioxo-2
      isoindolineethanesulfonic acid were also desulfonated at significant rates. Among
      the cosubstrates tested, only alpha-ketoglutarate (Km = 11 microM) supported
      significant dioxygenase activity.

PMID- 9287301
TI  - Identification of S100b protein as copper-binding protein and its suppression of
      copper-induced cell damage.
AB  - We have isolated from bovine brain a protein with a high capacity to inhibit the
      copper ion-catalyzed oxidation of L-ascorbate and identified it as S100b protein,
      an EF-hand calcium-binding protein, by sequencing its proteolytic peptides.
      Copper binding studies showed that this protein has four copper-binding sites per
      dimeric protein molecule with a dissociation constant of 0.46 microM and that in
      the presence of L-ascorbate, copper ions bind to a total of six binding sites
      with a great increase in affinity. Furthermore, we examined whether S100b protein
      can prevent copper-induced cell damage. Bovine S100b protein was found to
      suppress dose-dependently the hemolysis of mouse erythrocytes induced by CuCl2.
      We transformed Escherichia coli cells with pGEX-5X-3 vector containing a cDNA for
      rat S100b protein, so that this protein could be expressed as a fusion protein
      with glutathione S-transferase. The transformed cells were demonstrated to be
      markedly resistant to a treatment with CuCl2 plus H2O2 as compared with the
      control cells expressing glutathione S-transferase alone. These results indicate
      that S100b protein does suppress oxidative cell damage by sequestering copper
      ions.

PMID- 9287302
TI  - Isolation, expression, and regulation of the pgr1(+) gene encoding glutathione
      reductase absolutely required for the growth of Schizosaccharomyces pombe.
AB  - The pgr1(+) gene encoding glutathione reductase (GR, EC 1.6.4.2) was isolated
      from Schizosaccharomyces pombe using a polymerase chain reaction fragment as a
      probe. The gene consists of two exons and an intron of 55 nucleotides, encoding a
      polypeptide of 465 amino acids (50,238 Da) with conserved residues characteristic
      of GR. The transcriptional start site was localized at 239 nucleotides upstream
      from the ATG initiation codon. The level of transcript as well as the GR enzyme
      activity increased more than 11-fold when the cloned pgr1(+) gene was expressed
      on a multicopy plasmid. This overexpression conferred on S. pombe cells more
      resistance against menadione, a redox cycling agent, but not against H2O2. The
      level of pgr1(+) transcripts increased by treatment with oxidants such as
      menadione, cumene hydroperoxide, and diamide. It also increased by treatment with
      high osmolarity, heat shock, or at the stationary growth phase. The deletion of
      the pap1(+) gene encoding an AP-1 homolog in S. pombe caused reduction in the
      pgr1(+) gene expression. Furthermore, Deltapap1 cells lost the inducibility of
      pgr1(+) gene expression by the above stresses, implying that Pap1 is involved in
      general stress-inducible gene expression. When the pgr1(+) gene was disrupted,
      the haploid spores were not viable. Repression of nmt1 promoter-driven pgr1(+)
      expression by thiamine caused cessation of growth, which was rescued by the
      episomal pgr1(+) gene. These results indicate that GR activity, which efficiently
      reduces GSSG, is essentially required for the growth of S. pombe, unlike in
      Saccharomyces cerevisiae or Escherichia coli.

PMID- 9287303
TI  - Circular dichroism and 1H NMR studies on the structures of peptides derived from
      the calmodulin-binding domains of inducible and endothelial nitric-oxide synthase
      in solution and in complex with calmodulin. Nascent alpha-helical structures are
      stabilized by calmodulin both in the presence and absence of Ca2+.
AB  - There exist two types of nitric-oxide synthase (NOS); constitutive isozymes that
      are activated by binding calmodulin in response to elevated Ca2+ and an inducible
      isozyme that binds calmodulin regardless of Ca2+. To study the structural basis
      of the difference in Ca2+ sensitivity, we have designed synthetic peptides of
      minimal lengths derived from the calmodulin-binding domain of endothelial NOS
      (eNOS) and that of macrophage NOS (iNOS). A peptide, KRREIPLKVLVKAVLFACMLMRK,
      derived from human iNOS sequence, retained the ability to bind to calmodulin both
      in the presence and absence of Ca2+, while a peptide derived from human eNOS
      sequence, RKKTFKEVANAVKISASLMG, bound to calmodulin only in the presence of Ca2+.
      Circular dichroism and two-dimensional 1H nuclear magnetic resonance studies
      suggested that both peptides assume nascent alpha-helical structures in aqueous
      solution. When mixed with calmodulin, both peptides showed circular dichroism
      spectra characteristic for alpha-helix. In contrast to other target proteins, the
      addition of iNOS peptide to calmodulin did not affect the Ca2+ binding of
      calmodulin appreciably. The peptide derived from the calmodulin-binding domain of
      iNOS, therefore, binds in alpha-helical structures both to Ca2+-calmodulin and
      apo-calmodulin, which is unique among various target proteins of calmodulin.

PMID- 9287304
TI  - Mutation of tyrosine 383 in leukotriene A4 hydrolase allows conversion of
      leukotriene A4 into 5S,6S-dihydroxy-7,9-trans-11,14-cis-eicosatetraenoic acid.
      Implications for the epoxide hydrolase mechanism.
AB  - Leukotriene A4 hydrolase is a bifunctional zinc metalloenzyme that catalyzes the
      final step in the biosynthesis of the proinflammatory mediator leukotriene B4. In
      previous studies with site-directed mutagenesis on mouse leukotriene A4
      hydrolase, we have identified Tyr-383 as a catalytic amino acid involved in the
      peptidase reaction. Further characterization of the mutants in position 383
      revealed that [Y383H], [Y383F], and [Y383Q] leukotriene A4 hydrolases catalyzed
      hydrolysis of leukotriene A4 into a novel enzymatic metabolite. From analysis by
      high performance liquid chromatography, gas chromatography/mass spectrometry of
      material generated in the presence of H216O or H218O, steric analysis of the
      hydroxyl groups, treatment with soybean lipoxygenase, and comparison with a
      synthetic standard, the novel metabolite was assigned the structure 5S, 6S
      dihydroxy-7,9-trans-11,14-cis-eicosatetraenoic acid (5S,6S-DHETE). The kinetic
      parameters for the formation of 5S,6S-DHETE and leukotriene B4 were found to be
      similar. Also, both activities were susceptible to suicide inactivation and were
      equally sensitive to inhibition by bestatin. Moreover, from the stereochemical
      configuration of the vicinal diol, it could be inferred that 5S, 6S-DHETE is
      formed via an SN1 mechanism involving a carbocation intermediate, which in turn
      indicates that enzymatic hydrolysis of leukotriene A4 into leukotriene B4 follows
      the same mechanism. Inasmuch as soluble epoxide hydrolase utilizes leukotriene A4
      as substrate to produce 5S,6R-DHETE, our results also suggest a functional
      relationship between leukotriene A4 hydrolase and xenobiotic epoxide hydrolases.

PMID- 9287305
TI  - The guanylyl cyclase-deficient mouse defines differential pathways of natriuretic
      peptide signaling.
AB  - A genetic model of salt-resistant hypertension has been developed recently
      through disruption of the guanylyl cyclase-A (GC-A) natriuretic peptide receptor
      gene (Lopez, M. J., Wong, S. K., Kishimoto, I., Dubois, S., Mach, V., Friesen,
      J., Garbers, D. L., and Beuve, A. (1995) Nature 378, 65-68). These genetically
      altered mice were used to determine which of the natural peptides with
      natriuretic peptide-like structures regulate blood pressure through the GC-A
      receptor. Atrial natriuretic peptide (ANP) or B-type natriuretic peptide (BNP)
      half-maximally relaxed precontracted aortic rings in wild-type mice at about 24
      nM, but failed to relax such aortas in GC-A null mice, even at micromolar
      concentrations. C-type natriuretic peptide (CNP), in contrast, caused half
      maximal relaxation at concentrations of 335 and 146 nM in aortas from either wild
      type or null mice, respectively, suggesting that this peptide acted through a
      receptor other than GC-A. Since the in vitro results with aortic smooth muscle do
      not necessarily reflect the physiology of the smaller blood vessels important in
      blood pressure regulation, the blood pressures of conscious mice infused with the
      various peptides were determined. ANP caused decreases in blood pressure when
      infused at rates of 500 ng/kg/min, a rate which resulted in a plasma
      concentration of 0.8 nM. In the null mice, in contrast, ANP failed to lower blood
      pressure even at infusion rates of 50 microg/kg/min. Much higher infusion rates
      for CNP (50 microg/kg/min), which yielded final plasma concentrations of 18.3 nM,
      were required to lower blood pressure in wild-type mice, but the effects of CNP
      were not altered in GC-A null mice. Thus, two natriuretic peptides (ANP, BNP) act
      through GC-A whereas another (CNP) acts through another receptor to regulate
      blood pressure.

PMID- 9287306
TI  - Agonistic and antagonistic variants of ciliary neurotrophic factor (CNTF) reveal
      functional differences between membrane-bound and soluble CNTF alpha-receptor.
AB  - Ciliary neurotrophic factor (CNTF) drives the sequential assembly of a receptor
      complex containing the ligand-specific alpha-receptor subunit (CNTFR) and the
      signal-transducing beta-subunits gp130 and leukemia inhibitory factor receptor
      beta (LIFR). CNTFR can function in either membrane-bound or soluble forms. The
      membrane-bound form mediates the neuronal actions of CNTF, whereas the soluble
      form serves to confer cytokine responsiveness to non-neuronal cells expressing
      gp130 and LIFR. The objective of this work was to analyze whether the two
      receptor isoforms differ in their ability to interact functionally with CNTF and
      related proteins. Two new types of CNTF variants, characterized by weakened
      interactions with either CNTFR or both LIFR and gp130, were developed, and the
      biological activities of these and other mutants were determined in non-neuronal
      versus neuronal cells, as well as in non-neuronal cells transfected with an
      expression vector for CNTFR. Membrane anchoring of CNTFR was found to render the
      CNTF receptor complex relatively insensitive to changes in agonist affinity for
      either alpha- or beta-receptor subunits and to promote a more efficient
      interaction with a gp130-depleting antagonistic variant of CNTF. As a result of
      this phenomenon, which can be rationalized in terms of the multivalent nature of
      CNTF receptor interaction, CNTF variants display striking changes in receptor
      selectivity.

PMID- 9287307
TI  - Nitroxides increase the detectable amount of nitric oxide released from
      endothelial cells.
AB  - Nitroxides are known to exert superoxide dismutase-mimetic properties and to
      decrease O-2- and H2O2-mediated cytotoxicity. However, the effect of nitroxides
      on .NO homeostasis has not been studied yet. The present study investigates the
      effect of nitroxides on the detectable amount of .NO released by 3
      morpholinosydnonimine (SIN-1) and cultured endothelial cells. Cultured bovine
      aortic and atrial endothelial cells stimulated with 10 microM A23187 released a
      stable flux of .NO, as detected by .NO chemiluminescence. Addition of 100
      units/ml SOD or 10 microM of the nitroxides 4-hydroxy-2,2,6, 6
      tetramethylpiperidine-N-oxyl (TEMPOL), 3-carboxy-proxyl, and 3-ethoxycarbonyl
      proxyl, increased the chemiluminescence signal. The effect of these nitroxides on
      the amount of .NO released from cell monolayers was dose-dependent, with the
      highest efficacy between 30 and 100 microM. EPR spin trapping in SIN-1 solutions
      revealed the formation of .OH adducts from spontaneous dismutation of O-2 and
      concomitant reaction with H2O2. Both SOD and TEMPOL increased the signal
      intensity of the .OH adduct by accelerating the dismutation of O-2. The results
      of this study demonstrate that the SOD-mimetic activity of nitroxides increases
      the amount of bioavailable .NO in vitro.

PMID- 9287308
TI  - Partial agonist activity of 11-cis-retinal in rhodopsin mutants.
AB  - Rhodopsin, the photoreceptor molecule of the vertebrate rod cell, is a G protein
      coupled receptor. Rhodopsin consists of the opsin apoprotein and its 11-cis
      retinal chromophore, which is covalently bound to a specific lysine residue by a
      stable protonated Schiff base linkage. Rhodopsin activation occurs when light
      causes photoisomerization of the 11-cis chromophore to its all-trans form. The
      all-trans chromophore is the receptor agonist. The 11-cis-retinylidene
      chromophore is analogous pharmacologically to a potent inverse agonist of the
      receptor. We report here that replacement of a highly conserved glycine residue
      (Gly121) causes 11-cis-retinal to become a pharmacologic partial agonist.
      Although the mutant apoproteins do not display constitutive activity, they are
      active in the dark when bound to an 11-cis-retinylidene chromophore, or to a
      "locked" chromophore analogue, Ret-7. The degree of partial agonism is directly
      related to the size of the amino acid replacement at position 121, and it can be
      reversed by a specific second-site replacement of Phe261. Thus, mutation of
      Gly121 in rhodopsin causes 11-cis-retinal to act as a partial agonist rather than
      an inverse agonist, allowing the mutant pigment to activate transducin in the
      dark.

PMID- 9287309
TI  - Activity of ubiquitin-dependent pathway in response to oxidative stress.
      Ubiquitin-activating enzyme is transiently up-regulated.
AB  - Relations between the ubiquitin pathway and cellular stress have been noted, but
      data regarding responses of the ubiquitin pathway to oxidative stress are scanty.
      This paper documents the response of this pathway to oxidative stress in lens
      cells. A brief exposure of lens epithelial cells to physiologically relevant
      levels of H2O2 induces a transient increase in activity of the ubiquitin
      dependent pathway. Ubiquitin conjugation activity was maximal and increased 3. 5
      9.2-fold over the activity noted in untreated cells by 4 h after removal of H2O2.
      By 24 h after removal of H2O2, ubiquitin conjugation activity returned to the
      level noted in untreated cells. In parallel to the changes in ubiquitin
      conjugation activity, the activity of ubiquitin-activating enzyme (E1), as
      determined by thiol ester formation, increased 2-6.7-fold during recovery from
      oxidation. Addition of exogenous E1 resulted in an increase in ubiquitin
      conjugation activity and in the levels of ubiquitin carrier protein (E2)
      ubiquitin thiol esters in both the untreated cells and the H2O2-treated cells.
      These data suggest that E1 is the rate-limiting enzyme in the ubiquitin
      conjugation process and that the increases in ubiquitin conjugation activity
      which are induced upon recovery from oxidation are primarily due to increased E1
      activity. The oxidation- and recovery-induced up-regulation of E1 activity is
      primarily due to post-synthetic events. Substrate availability and up-regulation
      of E2 activities also appear to be related to the enhancement in ubiquitinylation
      upon recovery from oxidative stress. The oxidation-induced increases in ubiquitin
      conjugation activity were associated with an increase in intracellular
      proteolysis, suggesting that the transient increase in ubiquitinylation noted
      upon recovery from oxidative stress may play a role in removal of damaged
      proteins from the cells.

PMID- 9287310
TI  - The phosphatidyl-myo-inositol anchor of the lipoarabinomannans from Mycobacterium
      bovis bacillus Calmette Guerin. Heterogeneity, structure, and role in the
      regulation of cytokine secretion.
AB  - Lipoarabinomannans are major mycobacterial antigens capable of modulating the
      host immune response; however, the molecular basis underlying the diversity of
      their immunological properties remain an open question. In this study a new
      extraction and purification approach was successfully applied to isolate ManLAMs
      (lipoarabinomannans with mannosyl extensions) from bacillus Calmette Guerin
      leading to the obtention of two types of ManLAMs namely parietal and cellular.
      Structurally, they were found to differ by the percentage of mannooligosaccharide
      caps, 76 and 48%, respectively, and also, thanks to a new analytical method, by
      the structure of the phosphatidyl-myo-inositol anchor lipid moiety. A novel fatty
      acid in the mycobacterium genus assigned to a 12-O-(methoxypropanoyl)-12
      hydroxystearic acid was the only fatty acid esterifying C-1 of the glycerol
      residue of the parietal ManLAMs, while the phosphatidyl unit of the cellular
      ManLAMs showed a large heterogeneity due to a combination of palmitic and
      tuberculostearic acid. Finally, parietal and cellular ManLAMs were found to
      differentially affect interleukin-8 and tumor necrosis factor-alpha secretion
      from human dendritic cells. We show that parietal but not cellular ManLAMs were
      able to stimulate tumor necrosis factor-alpha secretion from dendritic cells.
      From these studies we propose that the 1-[12-O-(methoxypropanoyl)-12
      hydroxystearoyl]-sn-glycerol part is the major cytokine-regulating component of
      the ManLAMs. It seems likely that modification of the ManLAM lipid part, which
      may occur in hostile environments, could regulate macrophagic mycobacterial
      survival by altering cytokine stimulation.

PMID- 9287311
TI  - Expression of alpha-1,3-galactose and other type 2 oligosaccharide structures in
      a porcine endothelial cell line transfected with human alpha-1,2
      fucosyltransferase cDNA.
AB  - The binding of xenoreactive natural antibodies to the Galalpha1-3Galbeta1-4GlcNAc
      (alpha-galactose) oligosaccharide epitope on pig cells activates the recipient's
      complement system in pig to primate xenotransplantation. Expression of human
      alpha-1, 2-fucosyltransferase in pigs has been proposed as a strategy for
      reducing the expression level of the alpha-galactose epitope, thereby rendering
      the pig organs more suitable for transplantation into humans. The aim of this
      study was to examine how the cell surface expression of alpha-galactose, H, and
      related fucosylated and sialylated structures on a pig liver endothelial cell
      line is affected by transfection of human alpha-1,2-fucosyltransferase cDNA.
      Nontransfected and mock-transfected cells expressed alpha-galactose, alpha-2,3
      sialylated, and alpha-2,6-sialylated epitopes strongly, with low level expression
      of type 2 H and LewisX. By contrast, expression of the H epitope was increased 5
      8-fold in transfected cells with a 40% reduction in the expression of alpha
      galactose epitope and a 50% decrease in sialylation, as measured by binding of
      Maackia amurensis and Sambuccus nigra agglutinins. LewisX expression was reduced
      to background levels, while the LewisY neoepitope was induced in human alpha-1,2
      fucosyltransferase-expressing pig cells. The activities of endogenous alpha-1,3
      galactosyltransferase, alpha-1,3-fucosyltransferases, and alpha-2,3- and alpha-2,
      6-sialyltransferases acting on lactosamine were unaffected. Our results show that
      a reduction in alpha-galactose epitope expression in porcine endothelial cells
      transfected with human alpha-1, 2-fucosyltransferase cDNA may be achieved but at
      the expense of considerable distortion of the overall cell surface glycosylation
      profile, including the appearance of carbohydrate epitopes that are absent from
      the parent cells.

PMID- 9287312
TI  - Requirement of the caspase-3/CPP32 protease cascade for apoptotic death following
      cytokine deprivation in hematopoietic cells.
AB  - Hematopoietic cytokines transduce cell survival signals, which are distinct from
      the signals necessary for the stimulation of DNA synthesis. Recently, the Ras and
      phosphatidylinositol 3-kinase pathways have been shown to play important roles in
      preventing apoptosis in various cell types, e.g. hematopoietic cells and neuronal
      cells. Withdrawal of cytokine(s), in turn, results in rapid inactivation of these
      survival pathways and eventually leads to cell death accompanied by the hallmarks
      of apoptosis. However, the mechanism of cell death caused by cytokine deprivation
      has not been fully elucidated. In this study, we demonstrate that caspase
      3/CPP32, a member of the caspase/interleukin-1beta-converting enzyme family, is
      activated upon interleukin (IL)-3 deprivation in IL-3-dependent cells as well as
      IL-2 deprivation in IL-2-dependent cells. In addition, poly(ADP-ribose)
      polymerase, a cellular substrate for the caspase family proteases, was degraded
      into apoptotic fragments in both cell lines after cytokine removal. Furthermore,
      inhibition of a caspase family protease by synthetic peptides suppressed
      apoptotic death. These results indicate that the activation of a caspase-like
      protease(s) is required for the progression of apoptosis following cytokine
      deprivation. However, readdition of IL-3 did not restore the proliferative
      potential of the cells that survived in the presence of the peptide inhibitor
      after IL-3 depletion. Therefore, cellular commitment to apoptosis appears to
      precede the activation of a caspase-like protease(s).

PMID- 9287313
TI  - Multiple dimeric forms of human CD69 result from differential addition of N
      glycans to typical (Asn-X-Ser/Thr) and atypical (Asn-X-cys) glycosylation motifs.
AB  - CD69 is expressed on the surface of all hematopoietically derived leukocytes and
      is suggested to function as a multipurpose cell-surface trigger molecule
      important in the development and activation of many different cell types. Human
      CD69 contains only a single consensus sequence for N-linked oligosaccharide
      addition within its extracellular domain (Asn-Val-Thr), yet exists as two
      distinct glycoforms that are assembled together into disulfide-linked homodimers
      and heterodimers. The molecular basis for human CD69 heterogeneity has remained
      elusive. In the current report we show that human CD69 glycoforms are generated
      before the egress of CD69 proteins from the endoplasmic reticulum to the Golgi
      and are synthesized under conditions where Golgi processing is inhibited,
      effectively ruling out the possibility that CD69 heterogeneity results from the
      differential processing of a single glycosylation site in the Golgi complex.
      Importantly, these data demonstrate that contrary to current belief, not one but
      two sites for N-glycan addition exist within the human CD69 extracellular domain
      and identify the second, "cryptic" CD69 N-glycan attachment site as the atypical
      Cys-containing glycosylation motif, Asn-Ala-Cys. The results in this study
      provide a molecular basis for human CD69 heterogeneity and show that multiple
      dimeric forms of human CD69 result from the variable addition of N-glycans to
      atypical and typical glycosylation motifs within the CD69 extracellular domain.

PMID- 9287314
TI  - Human fibroblasts prefer mannose over glucose as a source of mannose for N
      glycosylation. Evidence for the functional importance of transported mannose.
AB  - Mannose in N-linked oligosaccharides is assumed to be derived primarily from
      glucose through phosphomannose isomerase (PMI). The discovery of mammalian
      mannose-specific transporters that function at physiological concentrations
      suggested that mannose might directly contribute to oligosaccharide synthesis. To
      determine the relative contribution of glucose and mannose, human fibroblasts
      were labeled with either [2-3H]mannose or [1,5,6-3H]glucose at the same specific
      activity, and the N-linked chains were released by PNGase F digestion. Most of
      the trichloroacetic acid-precipitable [3H]mannose label was released by this
      digestion, but only about 10% of the trichloroacetic acid-precipitable material
      was released from cells labeled with [1,5,6-3H]glucose. Both sugars labeled a
      similar array of oligosaccharides, and acid hydrolysis of these chains showed
      that [2-3H]mannose contributed 65-75% of the [3H]mannose in cells labeled for 1
      h, despite the 100-fold higher concentration of exogenous glucose. Mannose
      consumption and [2-3H]mannose utilization were within the range of rates expected
      for mannose transport via the mannose-specific transporter. About 7-14% of the [2
      3H]mannose is used for glycosylation, while the rest (86-93%) is catabolized to
      3H2O via PMI. Increasing the exogenous mannose concentration beyond mannose
      transporter saturation results in the conversion of >99% of [2-3H]mannose into
      3H2O. Long term labeling of cells with [2-3H]mannose showed that the specific
      activity of mannose in glycoproteins reached 77% of the specific activity of [2
      3H]mannose added to the medium. These results show that when fibroblasts are
      provided with physiological concentrations of mannose, they use the mannose
      specific transporter to supply the majority of mannose needed for glycoprotein
      synthesis. PMI may normally be used to catabolize excess mannose rather than to
      primarily supply Man-6-P for glycoprotein synthesis.

PMID- 9287315
TI  - Betagamma subunits of pertussis toxin-sensitive G proteins mediate A1 adenosine
      receptor agonist-induced activation of phospholipase C in collaboration with
      thyrotropin. A novel stimulatory mechanism through the cross-talk of two types of
      receptors.
AB  - COS-7 cells were transiently transfected with human thyrotropin receptor and dog
      A1 adenosine receptor cDNAs. An A1 agonist, N6-(L-2-phenylisopropyl) adenosine
      (PIA), which is ineffective alone, enhanced the thyrotropin (TSH)-induced
      inositol phosphate production, reflecting phospholipase C (PLC) activation, but
      inhibited the TSH-induced cAMP accumulation, reflecting adenylyl cyclase
      inhibition. These PIA-induced actions were completely inhibited by pertussis
      toxin (PTX) treatment. Moreover, in the cells expressing a PTX-insensitive mutant
      of Gi2alpha or Gi3alpha, in which a glycine residue was substituted for a
      cysteine residue to be ADP-ribosylated by PTX, at the fourth position of the C
      terminus, PIA effectively exerted both stimulatory and inhibitory effects on the
      TSH-induced actions although the cells were treated with the toxin.
      Overexpression of the betagamma subunits of the G proteins enhanced the TSH
      induced inositol phosphate production without any significant effect on the cAMP
      response; under these conditions, PIA did not further increase the elevated
      inositol phosphate response to TSH. On the contrary, overexpression of a
      constitutively active mutant of Gi2alpha, in which the guanosine triphosphatase
      activity is lost, inhibited the TSH-induced cAMP accumulation but hardly affected
      the inositol phosphate response; under these conditions, PIA never exerted
      further inhibitory effects on the cAMP response to TSH. In contrast to the case
      of the TSH-induced inositol phosphate response, the response to a constitutively
      active G11alpha mutant was not appreciably affected, and that to NaF was rather
      inhibited by PIA and overexpression of the betagamma subunits. Taken together,
      these results suggest that a single type of PTX-sensitive G protein mediates the
      A1 adenosine receptor-linked modulation of two signaling pathways in
      collaboration with an activated thyrotropin receptor; alpha subunits of the PTX
      sensitive G proteins mediate the inhibitory action on adenylyl cyclase, and the
      betagamma subunits mediate the stimulatory action on PLC. In the case of the
      latter stimulatory action on PLC, the betagamma subunits may not directly
      activate PLC. The possible mechanism by which betagamma subunits enhance the TSH
      induced PLC activation is discussed.

PMID- 9287316
TI  - Equilibrium and kinetic study of the conformational transition toward the active
      state of p21Ha-ras, induced by the binding of BeF3- to the GDP-bound state, in
      the absence of GTPase-activating proteins.
AB  - Hitherto ras-related GTP-binding proteins have been considered not to bind
      phosphate analogs (Kahn, R. A. (1991) J. Biol. Chem. 266, 15595-15597), at least
      in the absence of activating proteins (Mittal, R., Reza, M., Goody, R., and
      Wittinghofer, A. (1996) Science 273, 115-117). In this work, we have used a
      fluorescent active mutant (Y32W) of p21(Ha-)ras to demonstrate that BeF3- binds
      to the GDP. p21(Ha-ras) complex in the absence of activating proteins. It induces
      a conformational change leading to a state with fluorescence properties similar
      to those of the active state. The binding has a low affinity (Kd at 25 degrees C
      = 8.1 +/- 0.3 mM) and is endothermic (DeltaH = 22.3 +/- 1.6 kJ mol-1). The
      similarity between the GTP-bound form and the GDP.BeF3--bound form has been
      confirmed using lifetime analysis of the tryptophan fluorescence. The kinetic
      analysis of the process indicates that the binding can be divided into a first
      bimolecular step, which accounts for the association of the anion with its
      binding site, and a second step, which corresponds to an internal conformational
      transition of the GDP. BeF3-.p21(Ha-)ras complex to its final state. Both steps
      are endothermic (DeltaH1 = 15 +/- 2 kJ mol-1 and DeltaH2 = 8 +/- 2 kJ mol-1). The
      kinetically determined enthalpy change of 23 +/- 4 kJ mol-1 is in excellent
      agreement with the equilibrium analysis.

PMID- 9287317
TI  - Sp1-mediated transcriptional activation from the dominant promoter of the rat
      alpha1B adrenergic receptor gene in DDT1MF-2 cells.
AB  - In the rat liver, NF1 and CP1 bind to the major P2 promoter of the alpha1B
      adrenergic receptor gene to generate footprint II. Here we show that, in DDT1MF-2
      smooth muscle cells, the major protein bound to footprint II is not NF1 but Sp1,
      which binds to the 5'-portion of the footprint II sequence (footprint IIb).
      Mutational analyses demonstrate that the CCCGCG sequence in footprint IIb is
      critical for Sp1 binding and P2 promoter activity. A second GC box in the P2
      promoter also binds the Sp1 protein and contributes to the P2 promoter activity.
      Gel shift assays indicate that footprint II can bind Sp1, NF1, and CP1, and that
      the binding of these 3 proteins is mutually exclusive. This is also indicated by
      the results of functional cotransfection experiments, where transient
      overexpression of NF1 and Sp1 together caused a similar increase in the activity
      of a P2/CAT reporter construct as overexpression of either Sp1 or NF1 alone,
      indicating lack of additivity. The preferential interaction of footprint II with
      Sp1 in DDT1MF-2 cells and NF1 in liver appears to be due to low levels of NF1
      expression in DDT1MF-2 cells and low levels of Sp1 in liver. These observations
      suggest that NF1 and Sp1 are the major transcription factors involved in
      controlling the P2 promoter in liver versus DDT1MF-2 cells, respectively, which
      may be one of the mechanisms responsible for the complex tissue-specific
      regulation of the expression of the alpha1B adrenergic receptor gene.

PMID- 9287318
TI  - KIS is a protein kinase with an RNA recognition motif.
AB  - Protein phosphorylation is involved at multiple steps of RNA processing and in
      the regulation of protein expression. We present here the first identification of
      a serine/threonine kinase that possesses an RNP-type RNA recognition motif: KIS.
      We originally isolated KIS in a two-hybrid screen through its interaction with
      stathmin, a small phosphoprotein proposed to play a general role in the relay and
      integration of diverse intracellular signaling pathways. Determination of the
      primary sequence of KIS shows that it is formed by the juxtaposition of a kinase
      core with little homology to known kinases and a C-terminal domain that contains
      a characteristic RNA recognition motif with an intriguing homology to the C
      terminal motif of the splicing factor U2AF. KIS produced in bacteria has an
      autophosphorylating activity and phosphorylates stathmin on serine residues. It
      also phosphorylates in vitro other classical substrates such as myelin basic
      protein and synapsin but not histones that inhibit its autophosphorylating
      activity. Immunofluorescence and biochemical analyses indicate that KIS
      overexpressed in HEK293 fibroblastic cells is partly targetted to the nucleus.
      Altogether, these results suggest the implication of KIS in the control of
      trafficking and/or splicing of RNAs probably through phosphorylation of
      associated factors.

PMID- 9287319
TI  - Cellular binding of soluble CD14 requires lipopolysaccharide (LPS) and LPS
      binding protein.
AB  - The stimulation of nonmyeloid cells by lipopolysaccharide (LPS) is mediated by
      the serum protein, soluble CD14 (sCD14). We have examined the interaction of
      sCD14 with whole cells using a biologically active radiolabeled sCD14 molecule as
      a ligand. Specific binding of sCD14 to nonmyeloid cells is detected only when it
      is first incubated with both LPS and the serum LPS-binding protein (LBP). Through
      the use of an anti-CD14 monoclonal antibody, we demonstrate that sCD14 must
      interact with LPS in order for cellular binding to occur. Although LBP is
      traditionally known to function as a catalyst in the transfer of LPS to sCD14,
      our results reveal that LBP is actually a physical part of sCD14-containing, cell
      associating complexes. The LPS- and LBP-dependent cell surface binding of sCD14
      appears to be distinct from events leading to cell stimulation, since certain
      anti-CD14 and anti-LBP monoclonal antibodies have different effects on cellular
      binding versus cellular activation. Bound sCD14 is internalized, indicating that
      the LBP- and LPS-dependent binding of sCD14 may represent a novel general
      mechanism by which nonmyeloid cells clear LPS.

PMID- 9287321
TI  - Turnover of heparan sulfate depends on 2-O-sulfation of uronic acids.
AB  - To study how the pattern of sulfation along a heparan sulfate chain affects its
      turnover, we examined heparan sulfate catabolism in wild-type Chinese hamster
      ovary cells and mutant pgsF-17, defective in 2-O-sulfation of uronic acid
      residues (Bai, X., and Esko, J. D. (1996) J. Biol. Chem. 271, 17711-17717).
      Heparan sulfate from the mutant contains normal amounts of 6-O-sulfated
      glucosamine residues and iduronic acid and somewhat higher levels of N-sulfated
      glucosamine residues but lacks any 2-O-sulfated iduronic or glucuronic acid
      residues. Pulse-chase experiments showed that both mutant and wild-type cells
      transport newly synthesized heparan sulfate proteoglycans to the plasma membrane,
      where they shed into the medium or move into the cell through endocytosis.
      Internalization of the cell-associated molecules leads to sequential
      endoglycosidase (heparanase) fragmentation of the chains and eventual lysosomal
      degradation. In wild-type cells, the chains begin to degrade within 1 h, leading
      to the accumulation of intermediate (10-20-kDa) and small (4-7-kDa)
      oligosaccharides. Mutant cells did not generate these intermediates, although
      internalization and intracellular trafficking of the heparan sulfate chains
      appeared normal, and the chains degraded with normal kinetics. This difference
      was not due to defective heparanase activities in the mutant, since cytoplasmic
      extracts from mutant cells cleaved wild-type heparan sulfate chains in vitro.
      Instead, the heparan sulfate chains from the mutant were relatively resistant to
      degradation by cellular heparanases. These findings suggest that 2-O-sulfated
      iduronic acid residues in heparan sulfate are important for cleavage by
      endogenous heparanases but not for the overall catabolism of the chains.

PMID- 9287322
TI  - A betagamma dimer derived from G13 transduces the angiotensin AT1 receptor signal
      to stimulation of Ca2+ channels in rat portal vein myocytes.
AB  - A G protein composed of alpha13, beta1, and gamma3 subunits selectively couples
      the angiotensin AT1A receptors to increase cytoplasmic Ca2+ concentration
      ([Ca2+]i) in rat portal vein myocytes (Macrez-Lepretre, N., Kalkbrenner, F.,
      Morel, J. L., Schultz, G., and Mironneau, J. (1997) J. Biol. Chem. 272, 10095
      10102). We show here that Gbetagamma transduces the signal leading to stimulation
      of L-type Ca2+ channels. Intracellular dialysis through the patch pipette of a
      carboxyl-terminal anti-betacom antibody and a peptide corresponding to the
      Gbetagamma binding region of the beta-adrenergic receptor kinase 1 inhibited the
      stimulation of Ca2+ channels and the increase in [Ca2+]i evoked by angiotensin
      II. The Gbetagamma binding peptide did not prevent the dissociation of the
      heterotrimeric G protein into its subunits, as it did not block activation of
      phospholipase C-beta by Galphaq in response to stimulation of alpha1
      adrenoreceptors. Transient overexpression of the beta-adrenergic receptor kinase
      1 fragment and of Galpha subunits also inhibited the angiotensin II-induced
      increase in [Ca2+]i. Both anti-alpha13 antibody and carboxyl-terminal alpha13
      peptide abrogated the angiotensin II-induced stimulation of Ca2+ channels. We
      conclude that activation of angiotensin AT1 receptors requires all three alpha,
      beta, and gamma subunits of G13 for receptor-G protein interaction, whereas the
      transduction of the signal to L-type Ca2+ channels is mediated by Gbetagamma.

PMID- 9287323
TI  - The amino-terminal domain of CCR2 is both necessary and sufficient for high
      affinity binding of monocyte chemoattractant protein 1. Receptor activation by a
      pseudo-tethered ligand.
AB  - High affinity binding of monocyte chemoattractant protein 1 (MCP-1) requires the
      presence of the amino-terminal domain of CCR2, the MCP-1 receptor. Here we report
      that the 35 amino-terminal residues of CCR2, expressed as a membrane-bound fusion
      protein, bound MCP-1 with an affinity similar to that of the intact, wild-type
      receptor. Furthermore, the amino-terminal fusion protein enhanced, in trans,
      agonist-dependent activation of a CCR2 variant that was engineered to lack the
      high affinity binding sites for MCP-1. Mutation of highly conserved cysteines in
      the amino-terminal domain and third extracellular loop of CCR2, but not in the
      fusion protein, resulted in a dramatic loss of MCP-1 binding, suggesting the
      existence of a critical intramolecular disulfide bond that positions the amino
      terminal protein for ligand interaction. These data indicate that the amino
      terminal region of CCR2 is both necessary and sufficient for the high affinity
      binding of MCP-1 and provide the first direct evidence for activation of a
      chemokine receptor by a pseudo-tethered ligand. In this model, high affinity
      binding by the relatively short amino-terminal domain of CCR2 serves to tether
      MCP-1 and enhance low affinity interactions with distal regions of the receptor.

PMID- 9287320
TI  - Phosphorylation site mutations in the human multidrug transporter modulate its
      drug-stimulated ATPase activity.
AB  - In the human multidrug transporter (MDR1), three serine residues located in the
      "linker" region of the protein are targets of in vivo phosphorylation. These
      three serines, or all eight serines and threonines in the linker, were
      substituted by alanines (mutants 3A and 8A) or with glutamic acids (mutants 3E
      and 8E). The wild-type and mutant proteins were expressed in baculovirus-infected
      Spodoptera frugiperda (Sf9) ovarian insect cells, and the vanadate-sensitive,
      drug-stimulated ATPase activity was measured in isolated membrane preparations.
      The maximum drug-stimulated MDR1-ATPase activity was similar for the wild-type
      and the mutant proteins. However, wild-type MDR1, which is known to be
      phosphorylated in Sf9 membranes, and the 3E and 8E mutants, which mimic the
      charge of phosphorylation, achieved half-maximum activation of MDR1-ATPase
      activity at lower verapamil, vinblastine, or rhodamine 123 concentrations than
      the nonphosphorylatable 3A and 8A variants. For some other drugs (e.g.
      valinomycin or calcein acetoxymethylester) activation of the MDR1-ATPase for any
      of the mutants was indistinguishable from that of the wild-type protein. Kinetic
      analysis of the data obtained for the 3A and 8A MDR1 variants indicated the
      presence of more than one drug interaction site, exhibiting an apparent negative
      cooperativity. This phenomenon was not observed for the wild-type or the 3E and
      8E MDR1 proteins. The dependence of the MDR1-ATPase activity on ATP concentration
      was identical in the wild-type and the mutant proteins, and Hill plots indicated
      the presence of more than one functional ATP-binding site. These results suggest
      that phosphorylation of the linker region modulates the interaction of certain
      drugs with MDR1, especially at low concentrations, although phosphorylation does
      not alter the maximum level of MDR1-ATPase activity or its dependence on ATP
      concentration.

PMID- 9287324
TI  - Structure and expression of human fibroblast growth factor-10.
AB  - We isolated the cDNA encoding a novel member of the human fibroblast growth
      factor (FGF) family from the lung. The cDNA encodes a protein of 208 amino acids
      with high sequence homology (95.6%) to rat FGF-10, indicating that the protein is
      human FGF-10. Human FGF-10 as well as rat FGF-10 has a hydrophobic amino terminus
      ( approximately 40 amino acids), which may serve as a signal sequence. The
      apparent evolutionary relationships of human FGFs indicate that FGF-10 is closest
      to FGF-7. Chromosomal localization of the human FGF-10 gene was examined by in
      situ hybridization. The gene was found to map to the 5p12-p13 region. Human FGF
      10 (amino acids 40 to 208 with a methionine residue at the amino terminus) was
      produced in Escherichia coli and purified from the cell lysate. Recombinant human
      FGF-10 (approximately 19 kDa) showed mitogenic activity for fetal rat
      keratinizing epidermal cells, but essentially no activity for NIH/3T3 cells,
      fibroblasts. The specificity of mitogenic activity of FGF-10 is similar to that
      of FGF-7 but distinct from that of bFGF. In structure and biological activity,
      FGF-10 is similar to FGF-7.

PMID- 9287325
TI  - Determinants of apamin and d-tubocurarine block in SK potassium channels.
AB  - Small conductance calcium-activated potassium channels show a distinct
      pharmacology. Some, but not all, are blocked by the peptide toxin apamin, and
      apamin-sensitive channels are also blocked by d-tubocurarine. Cloned SK channels
      (small conductance calcium-activated potassium channel) recapitulate these
      properties. We have investigated the structural basis for these differences and
      found that two amino acid residues on either side of the deep pore are the
      primary determinants of sensitivity to apamin and differential block by d
      tubocurarine. Therefore, the pharmacology of SK channels compared with other
      potassium channels correlates with structural differences in the outer pore
      region. However, introduction of a tyrosine residue in the position analogous to
      that which determines sensitivity to external tetraethylammonium for voltage
      gated potassium channels endows SK channels with an equivalent tetraethylammonium
      sensitivity, indicating that the outer vestibules of the pores are similar. The
      pharmacology of channels formed in oocytes coinjected with SK1 and SK2 mRNAs, or
      with SK1-SK2 dimer mRNA, show that SK subunits may form heteromeric channels.

PMID- 9287326
TI  - SUG1, a component of the 26 S proteasome, is an ATPase stimulated by specific
      RNAs.
AB  - SUG1 is an integral component of the 26 S proteasome. Belonging to a novel
      putative ATPase family, it shares four conserved motifs characteristic of ATP
      dependent DNA/RNA helicases. Recombinant rat SUG1 (rSUG1) produced in Escherichia
      coli was highly purified and characterized in terms of its biochemical
      properties. The rSUG1 exhibited a Mg2+-dependent ATPase activity. The Km for ATP
      and Vmax of rSUG1 were 35 microM and 7 pmol of ATP/min/microg of protein,
      respectively. Both ATPase activity to release [32P]monophosphate and [32P]ATP
      labeling activity were coordinately affected by cold ATP severely, GTP and UTP
      moderately, and CTP little. Interestingly, the rSUG1 ATPase activity was
      stimulated by poly(U) and poly(C), but not by poly(A), poly(G), or by any forms
      of DNAs tested. A UV cross-linking assay also indicated poly(U)- and poly(C)
      stimulated labeling of rSUG1 with [alpha-32P]ATP. Moreover, the ATPase activity
      was facilitated by cellular poly(A)+ RNA, but not by poly(A)- RNA. RNA
      transcribed in vitro from cDNA encoding a b-Zip protein could stimulate the
      ATPase activity. This is the first report to demonstrate a specific RNA
      requirement for ATPase with respect to the proteasomal ATPases. Our present work
      suggests that SUG1 can specifically interact with protein-coding RNA (mRNA) and
      play some roles in mRNA metabolism.

PMID- 9287327
TI  - Existence of two heme B centers in cytochrome b561 from bovine adrenal chromaffin
      vesicles as revealed by a new purification procedure and EPR spectroscopy.
AB  - We have established a new purification procedure of cytochrome b561 from bovine
      adrenomedullary chromaffin vesicles. The heme content analysis of the purified
      sample indicated the presence of 1.7 molecules of heme B/cytochrome b561
      molecule. EPR spectroscopy of the purified enzyme in oxidized state showed that
      there were three types of low spin heme species. Two of them showed usual EPR
      signals at gz = 3.14 and gz = 2.84 arising from the same heme and were
      interconvertible depending on pH. The other species showed a highly anisotropic
      low spin signal at gz = 3.70, with a lower redox potential than the others, and a
      temperature-sensitive character. These properties are very similar to low
      potential cytochrome b (bL or b566) of the mitochondrial complex III, indicating
      that the gz = 3.70 species is derived from a heme component different from the
      one that shows the usual low spin EPR signals. Based on our new structural model,
      these two heme B prosthetic groups are likely to be located on both sides of the
      membranes in close contact with the ascorbic acid- and semidehydroascorbic acid
      binding sites, respectively, to facilitate the electron transfer across the
      membranes. This molecular architecture may provide a structural basis for the
      transmembrane electron transfer catalyzed by this hemoprotein.

PMID- 9287328
TI  - Autocrine nitric oxide modulates CD95-induced apoptosis in gammadelta T
      lymphocytes.
AB  - Gammadelta T lymphocytes play an important early role in the defense against
      pathogens. Their function is terminated by acquisition of susceptibility to CD95
      triggered apoptosis. Here we show that the regulation of this process depends on
      the activity of the endothelial NO synthase expressed by gammadelta T
      lymphocytes, which is modulated in an activation-dependent way. The effects of
      nitric oxide thus generated, mediated via cGMP generation, are exerted at at
      least two sites along the CD95 signaling cascade: one at, or upstream, and the
      other downstream of ceramide generation. At either site, nitric oxide/cGMP action
      is sufficient for protection from apoptosis. The effect of NO is selective for
      apoptosis induced by CD95 cross-linking, since it does not affect apoptotic
      program triggered by other stimuli. The evidence here reported demonstrates a new
      physiological role for nitric oxide, acting as a survival factor for T
      lymphocytes.

PMID- 9287329
TI  - Binding of NF-Y transcription factor to one of the cis-elements in the
      myeloperoxidase gene promoter that responds to granulocyte colony-stimulating
      factor.
AB  - The expression of the myeloperoxidase (MPO) gene is restricted to cells of the
      myeloid cell lineage and is induced by granulocyte colony-stimulating factor (G
      CSF). In this study, a series of deletion mutations was introduced in the
      promoter of the human MPO gene, which was then fused to the chloramphenicol
      acetyltransferase gene. The G-CSF-induced promoter activity was examined in mouse
      myeloid precursor FDC-P1 transformants that constitutively express the G-CSF
      receptor. A G-CSF-responsive element (GRE) in the MPO gene was found
      approximately 800 base pairs upstream from the transcription initiation site.
      When the 5'-flanking region of the human MPO gene contained this element, it
      yielded promoter activity in cells cultured with G-CSF but not in cells cultured
      with interleukin 3. Gel shift assays with the element showed that a specific
      nuclear factor(s) (NF/G-CSF) binds to the element. The NF/G-CSF was purified by
      affinity chromatography using an oligonucleotide of GRE. Protein sequence
      analysis of the purified NF/G-CSF indicated that NF/G-CSF is a ubiquitous
      transcription factor, NF-Y, which is composed of three subunits. The recombinant
      NF-Y was then shown to bind to GRE in a combination of the three subunits.

PMID- 9287330
TI  - Saccharomyces cerevisiae basic region-leucine zipper protein regulatory networks
      converge at the ATR1 structural gene.
AB  - Saccharomyces cerevisiae cells express a family of transcription factors
      belonging to the basic region-leucine zipper family. Two of these proteins, yAP-1
      and Gcn4p, are known to be involved in oxidative stress tolerance and general
      control of amino acid biosynthesis, respectively. Strains lacking the YAP1 or
      GCN4 structural gene have very different phenotypes, which have been taken as
      evidence that these transcriptional regulatory proteins control separate
      batteries of target genes. In this study, we provide evidence that both yAP-1 and
      Gcn4p control the expression of a putative integral membrane protein, Atr1p. Both
      yAP-1 and Gcn4p can elevate resistance to 3-amino-1,2,4-triazole and 4
      nitroquinoline-N-oxide but only if the ATR1 gene is intact. Expression of ATR1 is
      enhanced in the presence of constitutively active alleles of YAP1 and GCN4.
      Regulation of ATR1 transcription by yAP-1 and Gcn4p occurs through a common DNA
      element related to the yAP-1 recognition element found upstream of other yAP-1
      regulated genes. These data provide the first indication of overlap between the
      regulatory networks defined by yAP-1 and Gcn4p.

PMID- 9287331
TI  - A dominant role of the juxtamembrane region of the TrkA nerve growth factor
      receptor during neuronal cell differentiation.
AB  - All receptor tyrosine kinases share a common intracellular signaling machinery,
      including ras activation, whereas cellular responses vary from mitogenesis to
      cell differentiation. To investigate the structural basis for receptor tyrosine
      kinase action for nerve growth factor, the juxtamembrane region of TrkA was
      transferred to a corresponding region of the epidermal growth factor (EGF)
      receptor. The resulting chimeric receptor contains an additional Shc site,
      Tyr490, in the juxtamembrane region. In transfected PC12 cell lines, neuronal
      differentiation was observed with EGF treatment, as evidenced by increased
      neurite extension. The action of the chimeric receptor was correlated with
      prolonged activation of MAP kinases and a 3-4-fold increase in
      phosphatidylinositol 3-kinase activity. The effect of the juxtamembrane chimera
      was dependent upon the Shc site at Tyr490, because expression of a chimeric
      receptor containing a Y490F mutation resulted in a complete loss of
      neuritogenesis by EGF treatment. These findings indicate that the juxtamembrane
      region of the TrkA receptor serves as a key functional domain that can confer a
      dominant effect upon neuronal differentiation.

PMID- 9287332
TI  - Topology of the integral membrane form of Escherichia coli SecA protein reveals
      multiple periplasmically exposed regions and modulation by ATP binding.
AB  - SecA insertion and integration into the Escherichia coli inner membrane is a
      critical step for the catalysis of protein translocation across this layer. To
      understand this step further, SecA topology was investigated. To determine which
      regions of SecA are periplasmically exposed, right-side out membrane vesicles
      were prepared from strains synthesizing monocysteine SecA variants produced by
      mutagenesis and probed with a membrane-impermeant sulfhydryl-labeling reagent. To
      determine which regions of SecA contain membrane-integration determinants,
      inverted inner membrane vesicles were subjected to proteolysis, and integral
      membrane fragments of SecA were identified with region-specific antibodies. The
      membrane association properties of various truncated SecA species produced in
      vivo were also determined. Our analysis indicates that the membrane topology of
      SecA is complex with amino-terminal, central, and carboxyl-terminal regions of
      SecA integrated into the membrane where portions are periplasmically accessible.
      Furthermore, the insertion and penetration of the amino-terminal third of SecA,
      which includes the proposed preprotein-binding domain, is subject to modulation
      by ATP binding. The importance of these studies to the cycle of membrane
      insertion and de-insertion of SecA that promotes protein translocation and SecA's
      proximity to the preprotein channel are discussed.

PMID- 9287334
TI  - The high affinity calcium-binding sites in the epidermal growth factor module
      region of vitamin K-dependent protein S.
AB  - Vitamin K-dependent protein S, a cofactor of the anticoagulant enzyme-activated
      protein C, has four epidermal growth factor (EGF)-like modules, all of which have
      one partially hydroxylated Asp (EGF 1; beta-hydroxyaspartic acid) or Asn (EGF 2,
      3, and 4; beta-hydroxyasparagine) residue. The three C-terminal modules have a
      typical Ca2+ binding sequence motif that is usually present in EGF modules with
      hydroxylated Asp/Asn residues. Using the chromophoric Ca2+ chelators Quin 2 and
      5,5'-Br2BAPTA, we have now determined the Ca2+ affinity of recombinant fragments
      containing EGF modules 1-3, 1-4, 2-3, and 2-4. EGF modules 1-4 and 2-4 each
      contains two very high affinity Ca2+-binding sites, i.e. with dissociation
      constants ranging from 10(-10) to 10(-8) M in the absence of salt and from 10(-8)
      to 10(-6) M in the presence of 0.15 M NaCl. In contrast, in EGF 1-3 and EGF 2-3,
      the Ca2+ affinity is 2-4 orders of magnitude lower. EGF 4 thus appears to have
      the highest Ca2+ affinity, and furthermore it seems to influence the Ca2+
      affinity of its immediate N-terminal neighbor EGF 3 by a factor of approximately
      230. In addition, EGF 4 seems to influence the Ca2+ affinity of EGF 2 by a factor
      of approximately 25. The Ca2+ affinity of the binding sites in EGF modules 3 and
      4 in fragments EGF 1-4 and EGF 2-4 is 10(3)-10(5)-fold higher than in the
      corresponding isolated modules, implying important contributions to the Ca2+
      affinity of each module from interactions with neighboring modules. This
      difference is much higher than the approximately 10-fold difference previously
      found in similar comparisons of EGF modules from fibrillin. However, the modules
      studied in protein S and fibrillin appear to have the similar Ca2+ ligands. The
      structural basis for the difference in Ca2+ affinity is not yet understood.

PMID- 9287333
TI  - Unliganded epidermal growth factor receptor dimerization induced by direct
      interaction of quinazolines with the ATP binding site.
AB  - Receptor dimerization is critical for signaling by the epidermal growth factor
      receptor (EGFR) tyrosine kinase. This occurs after binding of the receptor's
      extracellular domain by ligand or bivalent antibodies. The role of other receptor
      domains in dimerization is less clear, and there are no examples of dimers
      induced by direct perturbation of the EGFR kinase domain. Submicromolar
      concentrations of AG-1478 and AG-1517, quinazolines specific for inhibition of
      the EGFR kinase, induced reversible receptor dimerization in vitro and in intact
      A431 cells. Consistent with the inhibitory effect of quinazolines on receptor
      kinase activity, the dimers formed lacked a detectable Tyr(P) signal. Quinazoline
      induced EGFR dimerization was abrogated in vitro by ATP and the ATP analog adenyl
      5'-yl imidodiphosphate. Receptors with a single-point mutation in the ATP binding
      site as well as wild-type EGFR with a covalent modification of the ATP site
      failed to dimerize in response to AG-1478 and AG-1517. These data suggest that
      EGFR dimerization can be induced by the interaction of quinazolines at the ATP
      site in the absence of receptor ligand binding. In SKBR-3 cells, the quinazolines
      induced the formation of inactive EGFR/ErbB-2 heterodimers, potentially
      sequestering ErbB-2 from interacting with other coreceptors of the ErbB family.
      Structural studies of the quinazoline interaction with the EGFR tyrosine kinase
      domain should allow for an analysis of receptor-specific chemical features
      required for binding to the ATP site and disruption of signaling, a strategy that
      can be perhaps applied to other tumor cell receptor systems.

PMID- 9287335
TI  - One of two NTP binding sites in poliovirus RNA polymerase required for RNA
      replication.
AB  - The poliovirus RNA-dependent RNA polymerase (3Dpol) has been shown to contain two
      NTP binding sites by chemical cross-linking of oxidized nucleotide to the intact
      protein. Only one site (Lys-61) was shown to be essential for RNA chain
      elongation activity by purified enzyme; however, a full-length viral RNA, coding
      for an altered lysine residue (K276L) in the second site, generated virus with a
      minute plaque phenotype that rapidly reverted to a wild-type phenotype with Arg
      276 replacing Leu-276 in 3D. Viruses with lysine to leucine substitutions in
      other positions of the second binding site of their polymerase proteins grew with
      wild-type phenotype. To test the significance of the second binding site,
      poliovirus 3Dpol was generated with lysine (wild-type), leucine, or arginine at
      residue 276 and tested for NTP cross-linking using 32P-oxidized GTP. Analysis of
      cyanogen bromide peptides of each 3D preparation showed that the second NTP
      binding site had severely reduced NTP binding in mu276(Leu) but not in the
      revertant mu276(Arg), despite the reported requirement for lysine in the cross
      linking reaction. To eliminate the possibility that 32P-oxidized GTP cross-linked
      to Arg at residue 276, a model system was designed with unmodified amino acid or
      acetylated (alpha-amino) amino acid and 32P-oxidized GTP. Cross-linking to
      lysine, but not leucine or arginine, was observed thus eliminating the
      possibility that NTP could be cross-linked to residue 276 in 3D. We conclude that
      NTP binding at the second site in poliovirus 3D is at lysine residues at
      positions other than 276 (278 or 283), and nucleotide binding at these sites has
      no bearing on elongation activity or replication of the virus. Nucleotide binding
      only at the site including Lys-61 is essential for RNA replication.

PMID- 9287336
TI  - Electrostatic influence on the kinetics of ligand binding to
      acetylcholinesterase. Distinctions between active center ligands and fasciculin.
AB  - To explore the role that surface and active center charges play in electrostatic
      attraction of ligands to the active center gorge of acetylcholinesterase (AChE),
      and the influence of charge on the reactive orientation of the ligand, we have
      studied the kinetics of association of cationic and neutral ligands with the
      active center and peripheral site of AChE. Electrostatic influences were reduced
      by sequential mutations of six surface anionic residues outside of the active
      center gorge (Glu-84, Glu-91, Asp-280, Asp-283, Glu-292, and Asp-372) and three
      residues within the active center gorge (Asp-74 at the rim and Glu-202 and Glu
      450 at the base). The peripheral site ligand, fasciculin 2 (FAS2), a peptide of
      6.5 kDa with a net charge of +4, shows a marked enhancement of rate of
      association with reduction in ionic strength, and this ionic strength dependence
      can be markedly reduced by progressive neutralization of surface and active
      center gorge anionic residues. By contrast, neutralization of surface residues
      only has a modest influence on the rate of cationic m
      trimethylammoniotrifluoroacetophenone (TFK+) association with the active serine,
      whereas neutralization of residues in the active center gorge has a marked
      influence on the rate but with little change in the ionic strength dependence.
      Brownian dynamics calculations for approach of a small cationic ligand to the
      entrance of the gorge show the influence of individual charges to be in
      quantitative accord with that found for the surface residues. Anionic residues in
      the gorge may help to orient the ligand for reaction or to trap the ligand. Bound
      FAS2 on AChE not only reduces the rate of TFK+ reaction with the active center
      but inverts the ionic strength dependence for the cationic TFK+ association with
      AChE. Hence it appears that TFK+ must traverse an electrostatic barrier at the
      gorge entry imparted by the bound FAS2 with its net charge of +4.

PMID- 9287337
TI  - FAP52, a novel, SH3 domain-containing focal adhesion protein.
AB  - Src-homology 3 (SH3) domain is a 60-70-amino acid motif present in a large
      variety of signal transduction and cytoskeletal proteins. We used reverse
      transcriptase-polymerase chain reaction with degenerate and specific primers and
      chicken brain mRNA to clone a cDNA that codes for a novel SH3 domain-containing
      protein. The sequence predicts a 448-amino acid polypeptide with a molecular mass
      of 51, 971 daltons. In the amino terminus, it shows a very high propensity for
      alpha-helicity, suggesting coiled-coil and possibly a higher order oligomeric
      arrangement. In the carboxyl terminus, there is a unique SH3 sequence. In
      Northern blotting, a major 3.7-kilobase and a minor 7.2-kilobase transcript was
      detected in most chicken tissues. In immunofluorescence microscopy and
      immunoelectron microscopy on cultured chicken fibroblasts, the protein was
      localized to focal adhesions in which it showed a distinct codistribution with
      the focal adhesion proteins vinculin, talin, and paxillin. Phosphoamino acid
      analysis showed that in cultured chicken heart fibroblasts, the protein contains
      phosphoserine, but no phosphothreonine or phosphotyrosine, and that the
      phosphorylation is not dependent on fibronectin. We propose this protein the name
      FAP52, for Focal Adhesion Protein of 52 kDa, and suggest that it forms part of
      the multimolecular complex constituting focal adhesion sites.

PMID- 9287338
TI  - GAS6 mediates adhesion of cells expressing the receptor tyrosine kinase Axl.
AB  - Axl is a receptor tyrosine kinase that contains both immunoglobulin and
      fibronectin III repeats in its extracellular domain reminiscent of cell adhesion
      molecules. Expression of the receptor tyrosine kinase Axl in the 32D myeloid cell
      line permits aggregation of cells in response to treatment with the native ligand
      GAS6; this aggregation was not observed in untreated 32D-Axl cells nor in treated
      parental cells. This aggregation can be blocked by the addition of excess Axl
      extracellular domain peptide and does not require intracellular Axl kinase
      activity. Cell surface binding activity of GAS6 was mapped to distinct plasma
      membrane interacting domains that are separate from the GAS6 motifs that engage
      the Axl receptor. This suggests that aggregation is mediated by a heterotypic
      intercellular mechanism whereby cell-bound GAS6 interacts with Axl receptor on an
      adjacent cell. This mechanism is supported by our observation that GAS6 binds to
      32D parental cells which then permits their aggregation with untreated 32D-Axl
      cells. We have recently demonstrated that the GAS6-Axl interaction does not
      initiate mitogenesis in 32D cells. When considered with the adhesion results,
      these data suggest that an important biological function of the Axl-GAS6
      interaction is to mediate cell-cell binding.

PMID- 9287339
TI  - The surface region of the bifunctional vaccinia RNA modifying protein VP39 that
      interfaces with Poly(A) polymerase is remote from the RNA binding cleft used for
      its mRNA 5' cap methylation function.
AB  - VP39 is a single-domain, bifunctional viral protein, which acts at both ends of
      nascent mRNA. At the 5' end, it acts as a cap-specific 2'-O-methyltransferase. At
      the 3' end, it acts as a poly(A) polymerase processivity factor, requiring its
      direct association with poly(A) polymerase. Although crystallographic and
      biochemical data show the catalytic center and associated binding sites for
      VP39's methyltransferase function to be juxtaposed around a superficial cleft on
      the protein surface, surface regions required for VP39's mRNA 3' end modifying
      functions are not known. Here, we identify a surface region that interfaces
      directly with poly(A) polymerase, taking three independent approaches: (i)
      development of a direct in vitro dimerization assay, which is applied to numerous
      VP39 point mutants; (ii) identification of sites within VP39 that become
      protected from protease cleavage upon dimerization and further mutagenesis based
      upon these data; (iii) site-specific photo-cross-linking of VP39 to VP55. We find
      that the dimerization interface lies on a surface region remote from the
      methyltransferase cleft and contains a 3-5-residue "hot-spot," which is very
      sensitive to amino acid substitutions. Various other sites within VP39
      consistently became hypersensitive to protease cleavage upon interaction with
      VP55, indicating the occurrence of extensive conformational changes.

PMID- 9287340
TI  - An NADPH:FAD oxidoreductase from the valanimycin producer, Streptomyces
      viridifaciens. Cloning, analysis, and overexpression.
AB  - The valanimycin producer Streptomyces viridifaciens contains a two-component
      enzyme system that catalyzes the oxidation of isobutylamine to
      isobutylhydroxylamine. One component of this enzyme system is isobutylamine
      hydroxylase, and the other component is a flavin reductase. The gene (vlmR)
      encoding the flavin reductase required by isobutylamine hydroxylase has been
      cloned from S. viridifaciens by chromosome walking. The gene codes for a protein
      of 194 amino acids with a calculated mass of 21,265 Da and a calculated pI of
      10.2. Overexpression of the vlmR gene in Escherichia coli as an N-terminal His
      tag derivative yielded a soluble protein that was purified to homogeneity.
      Removal of the N-terminal His-tag from the overexpressed protein by thrombin
      cleavage also produced a soluble protein. Both forms of the protein exhibited a
      high degree of flavin reductase activity, and the thrombin-cleaved form
      functioned in combination with isobutylamine hydroxylase to catalyze the
      conversion of isobutylamine to isobutylhydroxylamine. Kinetic data indicate that
      the overexpressed protein utilizes FAD and NADPH in preference to FMN,
      riboflavin, and NADH. The deduced amino acid sequence of the VlmR protein
      exhibited similarity to several other flavin reductases that may constitute a new
      family of flavin reductases.

PMID- 9287341
TI  - The binding mode of calyculin A to protein phosphatase-1. A novel spiroketal
      vector model.
AB  - The catalytic subunits of serine/threonine protein phosphatases 1 and 2A are
      subject to inhibition by various toxins such as the microcystins, the nodularins,
      okadaic acid, tautomycin, and the calyculins. A recent paper (Bagu, J. R., Sykes,
      B. D, Craig, M. M., and Holmes, C. F. B. (1997) J. Biol. Chem. 272, 5087-5097)
      reported the successful docking of the crystal structure of calyculin A to the
      crystal structure of protein phosphatase-1. Unfortunately, the model presented
      there is based on the structure of the unnatural enantiomer of calyculin A and
      must therefore be incorrect. We have developed a spiroketal vector model which
      appears to account for the spatial orientation of the hydrophobic and basic
      chains extending from the spiroketal-phosphate core of calyculin A. The model
      also clearly demonstrates why the unnatural enantiomer of calyculin A does not
      fit properly into the pocket of the active site. Based on our model, we present a
      possible open binding mode for calyculin A in the enzyme. This open structure is
      conceptually similar to the predicted binding mode of the peptide inhibitor DARPP
      32 to the enzyme; the hydrophobic, metal-binding, and electrostatic interactions
      are all retained in this model.

PMID- 9287342
TI  - Identification of a 190-kDa vascular endothelial growth factor 165 cell surface
      binding protein on a human glioma cell line.
AB  - Vascular endothelial growth factor (VEGF) is an angiogenesis factor for which two
      signaling protein tyrosine kinase receptors, Flt1 and KDR, have been identified.
      We describe here a 190-kDa component present on a human glioma cell line that
      binds VEGF165 with high affinity. In contrast, VEGF121 is bound only with low
      affinity, suggesting that the C-terminal part of VEGF165 is important for
      interaction with the 190-kDa component. No internalization or stimulation of
      tyrosine phosphorylation was recorded after ligand binding to the 190-kDa
      component, suggesting that it may not be directly involved in signaling; its
      function may be to present ligand or stabilize ligand binding to signaling
      receptors.

PMID- 9287343
TI  - The amino terminus of insulin-responsive aminopeptidase causes Glut4
      translocation in 3T3-L1 adipocytes.
AB  - The insulin-responsive aminopeptidase (IRAP) is a constituent of the vesicles
      that contain the insulin-regulated glucose transporter (Glut4). Like Glut4, IRAP
      translocates to the cell surface in response to insulin. Microinjection into 3T3
      L1 adipocytes of a glutathione S-transferase (GST) fusion protein containing the
      cytosolic portion of IRAP (GST-IRAP-(1-109)), resulted in translocation of Glut4
      to the cell surface. Immunostaining of 3T3-L1 adipocytes for Glut4 showed that
      the percentage of cells with substantial cell surface Glut4 was 10% in
      unstimulated cells, 8% following injection of GST, and 27% following injection of
      GST-IRAP-(1-109). Increased cell surface Glut4 occurred within 5-10 min following
      injection and was maintained for at least 4 h. A fusion protein containing only
      28 amino acids from IRAP (GST-IRAP-(55-82)) was as effective in increasing cell
      surface Glut4 as stimulation with 100 nM insulin (44% versus 43%, respectively).
      In contrast to insulin-stimulated Glut4 translocation, the redistribution of
      Glut4 following injection of GST-IRAP-(55-82) was not blocked by wortmannin or co
      injection with a SH2 domain from the regulatory subunit of phosphatidylinositol 3
      kinase. These data suggest that the amino terminus of IRAP interacts with a
      retention/sorting protein that also regulates the distribution of Glut4 in
      insulin-responsive cells.

PMID- 9287344
TI  - Elevated homologous recombination activity in fanconi anemia fibroblasts.
AB  - It is widely believed that Fanconi anemia cells possess a reduced ability to
      repair inter-strand DNA cross-links. While the mechanism through which inter
      strand DNA cross-links are removed from mammalian chromosomes is unknown, these
      lesions are repaired via homologous recombination in lower eukaryotes and
      bacteria. Based on the hypothesis that a similar mechanism of DNA repair
      functions in mammalian somatic cells, we measured homologous recombination
      activity in diploid fibroblasts from healthy donors, and Fanconi anemia patients.
      Somewhat surprisingly, homologous recombination levels in nuclear protein
      extracts prepared from Fanconi anemia cells were nearly 100-fold higher than in
      extracts prepared from control cells. We observed a similar increase in the
      activity of a 100-kDa homologous DNA pairing protein in extracts from Fanconi
      anemia cells. Transfection studies confirmed that plasmid homologous
      recombination levels in intact Fanconi anemia cells were substantially elevated,
      compared with control cells. These results suggest that inappropriately elevated
      levels of homologous recombination activity may contribute to the genomic
      instability and cancer predisposition that characterize Fanconi anemia.

PMID- 9287345
TI  - Transcriptional control of the forkhead thyroid transcription factor TTF-2 by
      thyrotropin, insulin, and insulin-like growth factor I.
AB  - The hormonal regulation of both thyroglobulin and thyroperoxidase promoter
      activity in FRTL-5 thyroid cells takes place, at least in part, through a hormone
      responsive element to which the thyroid transcription factor TTF-2 binds. The TTF
      2 cDNA, encoded by the titf2 locus, has recently been cloned and classified as a
      member of the forkhead transcription factor family. Here, we demonstrate that TTF
      2 mRNA levels become undetectable in FRTL-5 thyroid cells cultured for 4 days in
      0.2% serum and in the absent of thyrotropin (TSH) and insulin. Addition of TSH,
      insulin or insulin-like growth factor I (IGF-I) to the culture medium increases
      the levels of this transcription factor in a dose- and time- dependent manner and
      requires ongoing protein synthesis. The TSH effect is greater than that produced
      by insulin or IGF-I and is similar to the effect produced by the cAMP analog
      forskolin. The TSH and insulin effects are additive. In all cases, the mRNA
      levels increase is accompanied by an increase in transcription rate, as
      demonstrated by run-off assays. These data demonstrate that the TTF-2 mRNA is
      under tight hormonal control. This is consistent with an important role for TTF-2
      as a mediator of the transcriptional activation of thyroid-specific genes
      (thyroglobulin and thyroperoxidase) by TSH via cAMP and by insulin through the
      IGF-I receptor.

PMID- 9287346
TI  - Identification of the membrane receptor binding domain of thyroglobulin. Insights
      into quality control of thyroglobulin biosynthesis.
AB  - The last stages of thyroglobulin maturation occur in the thyroid follicular lumen
      and include thyroid hormone formation and glycan completion. In this compartment,
      newly secreted thyroglobulins interact with a thyrocyte membrane receptor that
      prevents their premature lysosomal transfer and degradation. Both GlcNAc moieties
      and thyroglobulin peptide determinants are involved in receptor interaction. Here
      we used monoclonal antibodies (mAbs) directed against human thyroglobulin either
      to inhibit (mAb78) or to enhance (mAb240) the thyroglobulin binding and to
      identify the region of the thyroglobulin involved in the receptor recognition.
      Peptides containing the mAb epitopes were obtained by immunoscreening cyanogen
      bromide-derived native human thyroglobulin peptides and a cDNA thyroglobulin
      expression library. Three peptides, localized in the thyroglobulin N-terminal
      domain, were obtained. Peptides N1 (Ala1148-Gln1295) and N2 (Ser789-Met1008) were
      recognized by mAb240 and mAb78, respectively. None of them bound the receptor.
      The third peptide, N3 (Ser789-Met1172), (i) overlapped all or part of the N1 and
      N2 peptide sequences and was recognized by both mAbs, (ii) carried two complex
      glycans at Asn797 and Asn928, of which a subset presented accessible GlcNAc
      residues, and (iii) inhibited the thyroglobulin binding to FRTL5 cell membrane
      preparations. The N3 peptide includes tyrosine residues that have been reported
      to be involved in hormone formation. These results suggest that structural
      modifications closely associated with hormone formation within this domain act as
      sensors for the receptor interaction and thus for the intrafollicular retention
      or lysosomal homing of the prohormone.

PMID- 9287347
TI  - Phosphatidylinositol 3'-kinase-independent p70 S6 kinase activation by fibroblast
      growth factor receptor-1 is important for proliferation but not differentiation
      of endothelial cells.
AB  - p70(s6k) has a role in cell cycle progression in response to specific
      extracellular stimuli. The signal transduction pathway leading to activation of
      p70(s6k) by fibroblast growth factor receptor-1 (FGFR-1) was examined in FGF-2
      treated rat L6 myoblasts. p70(s6k) was activated in a biphasic and rapamycin
      sensitive manner. Although phosphatidylinositol 3'-kinase was not activated in
      the FGF-2 treated cells, as judged from in vitro and in vivo analyses, wortmannin
      and LY294002 treatment inhibited p70(s6k) activation. Inhibition of protein
      kinase C (PKC), by bisindolylmaleimide or by chronic phorbol ester treatment of
      the FGFR-1 cells, suppressed but did not block p70(s6k) activation. In cells
      expressing a point-mutated FGFR-1, Y766F, unable to mediate PKC activation,
      p70(s6k) was still activated, in a bisindolylmaleimide- and phorbol ester
      resistant manner. The involvement of S6 kinase in FGFR-1-dependent biological
      responses was examined in murine brain endothelial cells. In response to FGF-2,
      these cells differentiate to form tube-like structures in collagen gel cultures
      and proliferate when cultured on fibronectin. p70(s6k) was not activated in
      endothelial cells on collagen, whereas activation was observed during
      proliferation on fibronectin. In agreement with this finding, rapamycin inhibited
      the proliferative but not the differentiation response. Our results indicate that
      FGFR-1 mediates p70(s6k) activation by a phosphatidylinositol 3'-kinase
      independent mechanism that does not require PKC activation and, furthermore,
      proliferation, but not differentiation of endothelial cells in response to FGF-2,
      is associated with p70(s6k) activation.

PMID- 9287348
TI  - Isolation and characterization of a prenylcysteine lyase from bovine brain.
AB  - Prenylated proteins contain one of two isoprenoid lipids, either the 15-carbon
      farnesyl or the 20-carbon geranylgeranyl, covalently attached to cysteine
      residues at or near their C terminus. The cellular abundance of prenylated
      proteins, which can comprise up to 2% of total cellular protein, raises the
      question of how cells dispose of prenylcysteines produced during the normal
      turnover of prenylated proteins. We have identified and characterized a novel
      enzyme, which we term prenylcysteine lyase, that is capable of cleaving the
      thioether bond of prenylcysteines. The enzyme was isolated from bovine brain
      membranes and exhibits an apparent molecular mass of 63 kDa. The enzyme did not
      require NADPH as cofactor for prenylcysteine degradation, thus distinguishing it
      from cytochrome P450- and flavin-containing monooxygenases that catalyze S
      oxidation of thioethers. Purified prenylcysteine lyase shows similar kinetics in
      utilization of both farnesylcysteine and geranylgeranylcysteine as substrates,
      although Vmax is 2-fold higher with the former compound. Interaction of
      prenylcysteine substrates with the enzyme requires that they possess a free amino
      group; N-acetylated prenylcysteines and prenyl peptides are not substrates. These
      findings suggest that prenylcysteine lyase is a specific enzyme involved in
      prenylcysteine metabolism in mammalian cells, most likely comprising the final
      step in the degradation of prenylated proteins.

PMID- 9287349
TI  - Yeast DNA repair proteins Rad6 and Rad18 form a heterodimer that has ubiquitin
      conjugating, DNA binding, and ATP hydrolytic activities.
AB  - The RAD6 and RAD18 genes of Saccharomyces cerevisiae are required for
      postreplicative bypass of ultraviolet (UV)-damaged DNA and for UV mutagenesis.
      The RAD6 encoded protein is a ubiquitin conjugating enzyme, and RAD18 encodes a
      protein containing a RING finger motif and a nucleotide binding motif. Rad18 can
      be co-immunoprecipitated with Rad6, indicating that the two proteins exist in a
      complex in vivo. Here, we co-overproduce the two proteins using a yeast multicopy
      plasmid, purify the Rad6-Rad18 complex to near homogeneity, and show that the
      complex is heterodimeric. The Rad6-Rad18 heterodimer has ubiquitin conjugating
      activity, binds single-stranded DNA, and possesses single-stranded DNA-dependent
      ATPase activity. The Rad6-Rad18 complex provides the first example wherein a
      ubiquitin conjugating activity is physically associated with DNA binding and
      ATPase activities provided by an associated protein factor. The co-existence of
      these activities should provide the complex with the ability to recognize single
      stranded DNA resulting from stalling of the replication machinery at DNA damage
      sites and to recognize the components of the DNA replication machinery for
      ubiquitination by Rad6.

PMID- 9287350
TI  - Sustained activation of the extracellular signal-regulated kinase/mitogen
      activated protein kinase pathway is required for megakaryocytic differentiation
      of K562 cells.
AB  - The extracellular signal-regulated kinase (ERK), originally identified as a
      participant in mitogenic signaling, has recently been implicated in the signaling
      of cellular differentiation. To examine the role of the ERK/MAP kinase pathway in
      megakaryocytic differentiation of K562 cells, the effects of 12-O
      tetradecanoylphorbol-13-acetate (TPA) and bryostatin on ERK activation were
      determined. Both TPA and bryostatin are known to activate PKC but paradoxically
      have opposing effects on megakaryocytic differentiation. TPA, a differentiation
      inducer, caused sustained activation of ERK (>24 h), whereas bryostatin, a
      differentiation blocker, only transiently activated ERK ( approximately 6 h) and
      attenuated the activation of ERK by TPA. To confirm a requirement for sustained
      ERK activation for megakaryocytic differentiation, PD098059, a synthetic
      inhibitor of the MAP kinase kinase 1 (MEK1) was employed. Introduction of
      PD098059 at any time during the first 18 h of TPA treatment completely abrogated
      megakaryocytic differentiation of K562 cells. After 24 h of TPA treatment,
      introduction of PD098059 failed to block differentiation. Differentiation
      blockade by PD098059 occurred via inhibition of MEK because transfection of a
      constitutively active mutant of MEK2 could override the PD098059 blockade.
      Experiments with conditioned media suggested that sustained activation of the
      ERK/MAP kinase pathway promoted the autocrine secretion of megakaryocytic lineage
      determination factors.

PMID- 9287351
TI  - Direct interaction of the Rho GDP dissociation inhibitor with
      ezrin/radixin/moesin initiates the activation of the Rho small G protein.
AB  - The Rho GDP dissociation inhibitor (GDI) forms a complex with the GDP-bound form
      of the Rho family small G proteins and inhibits their activation. The GDP-bound
      form complexed with Rho GDI is not activated by the GDP/GTP exchange factor for
      the Rho family members, suggesting the presence of another factor necessary for
      this activation. We have reported that the Rho subfamily members regulate the
      ezrin/radixin/moesin (ERM)-CD44 system, implicated in reorganization of actin
      filaments. Here we report that Rho GDI directly interacts with ERM, initiating
      the activation of the Rho subfamily members by reducing the Rho GDI activity.
      These results suggest that ERM as well as Rho GDI and the Rho GDP/GTP exchange
      factor are involved in the activation of the Rho subfamily members, which then
      regulate reorganization of actin filaments through the ERM system.

PMID- 9287352
TI  - Positive effects of SH2 domain-containing tyrosine phosphatase SHP-1 on epidermal
      growth factor- and interferon-gamma-stimulated activation of STAT transcription
      factors in HeLa cells.
AB  - SHP-1 (also known as PTP1C, SHPTP-1, SHP, and HCP) is an SH2 domain-containing
      protein-tyrosine phosphatase. We have stably overexpressed the native form and a
      catalytically inactive cysteine to serine mutant of the enzyme, SHP-1-(Cys -->
      Ser), in human cervical carcinoma HeLa cells. Following stimulation of the cells
      with epidermal growth factor (EGF) and interferon-gamma (INF-gamma), signal
      transducers and activators of transcription (STAT) activity was analyzed by using
      two 32P-labeled DNA probes, namely hSIE which is derived from a high affinity
      mutant form of the serum-inducible element in the c-fos promotor and GAS which
      resembles the INF-gamma activation site. EGF induced hSIE binding activity only,
      and the activity was suppressed by approximately 70% when the inactive mutant
      form of SHP-1 was expressed but was essentially unaffected by expression of the
      native enzyme. INF-gamma treatment resulted in appearance of both hSIE and GAS
      binding activities. While expression of the inactive mutant reduced the
      activities by 30-50%, the native enzyme caused a 20-30% increase. Consistent with
      effects on STAT activation, altered SHP-1 expression also affected EGF-induced
      activation of the mitogen-activated protein kinase pathway; expression of SHP-1
      (Cys --> Ser) inhibited activity of MEK by approximately 25%, whereas expression
      of SHP-1 resulted in a approximately 25% increase. Further studies revealed that
      overexpression of SHP-1 caused decreased tyrosine phosphorylation of the EGF
      receptor and that EGF induced phosphorylation and recruitment of SHP-1. Together,
      the data suggest that SHP-1 is positively involved in EGF- and INF-gamma-induced
      STAT activation in non-hematopoietic HeLa cells and that, in the EGF signaling
      system, SHP-1 functions at least partly by modulating tyrosine phosphorylation of
      EGF receptor.

PMID- 9287353
TI  - Dependence on the motif YIPP for the physical association of Jak2 kinase with the
      intracellular carboxyl tail of the angiotensin II AT1 receptor.
AB  - Angiotensin II is the effector molecule of the renin-angiotensin system.
      Virtually all of its biochemical actions are mediated through a single class of
      cell-surface receptors called AT1. These receptors contain the structural
      features of the seven-transmembrane, G-protein-coupled receptor superfamily.
      Angiotensin II, acting through the AT1 receptor, also stimulates the Jak/STAT
      pathway by inducing ligand-dependent Jak2 tyrosine phosphorylation and
      activation. Here, we show that a glutathione S-transferase fusion protein
      containing the carboxyl-terminal 54 amino acids of the rat AT1A receptor
      physically binds to Jak2 in an angiotensin II-dependent manner. Deletional
      analysis, using both in vitro protocols and cell transfection analysis, showed
      that this association is dependent on the AT1A receptor motif YIPP (amino acids
      319-322). The wild-type AT1A receptor can induce Jak2 tyrosine phosphorylation.
      In contrast, an AT1A receptor lacking the YIPP motif is unable to induce ligand
      dependent phosphorylation of Jak2. Competition experiments with synthetic
      peptides suggest that each of the YIPP amino acids, including tyrosine 319, is
      important in Jak2 binding to the AT1A receptor. The binding of the AT1A receptor
      to the intracellular tyrosine kinase Jak2 supports the concept that the seven
      transmembrane superfamily of receptors can physically associate with
      enzymatically active intracellular proteins, creating a signaling complex
      mechanistically similar to that observed with growth factor and cytokine
      receptors.

PMID- 9287354
TI  - Complex formation between junctin, triadin, calsequestrin, and the ryanodine
      receptor. Proteins of the cardiac junctional sarcoplasmic reticulum membrane.
AB  - Several key proteins have been localized to junctional sarcoplasmic reticulum
      which are important for Ca2+ release. These include the ryanodine receptor,
      triadin, and calsequestrin, which may associate into a stable complex at the
      junctional membrane. We recently purified and cloned a fourth component of this
      complex, junctin, which exhibits homology with triadin and is the major 125I
      calsequestrin-binding protein detected in cardiac sarcoplasmic reticulum vesicles
      (Jones, L. R., Zhang, L., Sanborn, K., Jorgensen, A. O., and Kelley, J. (1995) J.
      Biol. Chem. 270, 30787-30796). In the present study, we have examined the binding
      interactions between the cardiac forms of these four proteins with emphasis
      placed on the role of junctin. By a combination of approaches including
      calsequestrin-affinity chromatography, filter overlay, immunoprecipitation
      assays, and fusion protein binding analyses, we find that junctin binds directly
      to calsequestrin, triadin, and the ryanodine receptor. This binding interaction
      is localized to the lumenal domain of junctin, which is highly enriched in
      charged amino acids organized into "KEKE" motifs. KEKE repeats are also found in
      the common lumenal domain of triadin, which likewise is capable of binding to
      calsequestrin and the ryanodine receptor (Guo, W., and Campbell, K. P. (1995) J.
      Biol. Chem. 270, 9027-9030). It appears that junctin and triadin interact
      directly in the junctional sarcoplasmic reticulum membrane and stabilize a
      complex that anchors calsequestrin to the ryanodine receptor. Taken together,
      these results suggest that junctin, calsequestrin, triadin, and the ryanodine
      receptor form a quaternary complex that may be required for normal operation of
      Ca2+ release.

PMID- 9287356
TI  - Primary structure and differential gene expression of three membrane forms of
      guanylyl cyclase found in the eye of the teleost Oryzias latipes.
AB  - Three cDNAs (OlGC3, OlGC4, and OlGC5) encoding membrane guanylyl cyclases were
      isolated from a medaka (Oryzias latipes) eye cDNA library. An open reading frame
      for OlGC3 predicted a protein of 1057 amino acids, and those for OlGC4 and OlGC5,
      1134 and 1151, respectively. These proteins consist of an apparent signal peptide
      (21 residues for OlGC3, 50 residues for OlGC4, and 48 residues for OlGC5) and a
      single transmembrane domain that divides the protein into an amino-terminal
      extracellular domain and a carboxyl-terminal intracellular domain that further
      divides into a kinase-like domain and a cyclase catalytic domain. Phylogenetic
      analysis with amino acid sequences of OlGC3, OlGC4, and OlGC5, as well as those
      of other membrane guanylyl cyclases, indicated that OlGC3, OlGC4, and OlGC5 are
      members of the sensory organ-specific guanylyl cyclase family. Reverse
      transcription-polymerase chain reaction and Northern blot analyses demonstrated
      that OlGC3, OlGC4, and OlGC5 transcripts are present in the eye, which contains
      more cGMP than the other organs. In addition to being expressed in the eye, OlGC3
      transcripts are also present in the brain, heart, liver, pancreas, and ovary,
      while OlGC4 is present in the liver and OlGC5 in the heart. Reverse transcription
      polymerase chain reaction analysis with RNA from unfertilized eggs and embryos
      showed that OlGC3 and OlGC5 are expressed both maternally and zygotically, while
      OlGC4 is expressed only zygotically, and that the zygotic expression of these
      three genes is differentially activated. These results suggest a structural and
      functional diversity of sensory organ-specific guanylyl cyclases in vertebrates.

PMID- 9287355
TI  - The basic helix-loop-helix-zipper transcription factor USF1 regulates expression
      of the surfactant protein-A gene.
AB  - Expression of the rabbit pulmonary surfactant protein A (SP-A) gene is lung
      specific, occurs primarily in type II cells, and is developmentally regulated. We
      previously identified two E-box-like enhancers, termed the distal binding element
      (DBE) and proximal binding element (PBE), in the 5'-flanking region of the rabbit
      SP-A gene. In the present study, the PBE was used to screen a rabbit fetal lung
      cDNA expression library; a cDNA insert was isolated which is highly similar in
      sequence to human upstream stimulatory factor 1 (hUSF1). By use of reverse
      transcription polymerase chain reaction, two isoforms of rabbit USF1 (rUSF1)
      mRNAs were identified in fetal rabbit lung and other tissues. The levels of rUSF1
      mRNAs reach a peak in fetal rabbit lung at 23 days gestation, in concert with the
      time of initiation of SP-A gene transcription. Binding complexes of nuclear
      proteins obtained from fetal rabbit lung tissue and isolated type II cells with
      the DBE and PBE were supershifted by the addition of anti-rUSF1 IgG. Binding
      activity was enriched in type II cells compared with lung fibroblasts.
      Overexpression of rUSF1s in A549 adenocarcinoma cells positively regulated SP-A
      promoter activity of cotransfected reporter gene constructs. It is suggested that
      rUSF1s, which bind to two E-box elements in the SP-A gene 5'-flanking region, may
      serve a key role in the regulation of SP-A gene expression in pulmonary type II
      cells.

PMID- 9287357
TI  - Interaction of factor IXa with factor VIIIa. Effects of protease domain Ca2+
      binding site, proteolysis in the autolysis loop, phospholipid, and factor X.
AB  - We previously identified a high affinity Ca2+ binding site in the protease domain
      of factor IXa involving Glu235 (Glu70 in chymotrypsinogen numbering; hereafter,
      the numbers in brackets refer to the chymotrypsin equivalents) and Glu245[80] as
      putative ligands. To delineate the function of this Ca2+ binding site, we
      expressed IXwild type (IXWT), IXE235K, and IXE245V in 293 kidney cells and
      compared their properties with those of factor IX isolated from normal plasma
      (IXNP); each protein had the same Mr and gamma-carboxyglutamic acid content.
      Activation of each factor IX protein by factor VIIa.Ca2+.tissue factor was normal
      as analyzed by sodium dodecyl sulfate-gel electrophoresis. The coagulant activity
      of IXaWT was approximately 93%, of IXaE235K was approximately 27%, and of
      IXaE245V was approximately 4% compared with that of IXaNP. In contrast,
      activation by factor XIa.Ca2+ led to proteolysis at Arg318-Ser319[150-151] in the
      protease domain autolysis loop of IXaE245V with a concomitant loss of coagulant
      activity; this proteolysis was moderate in IXaE235K and minimal in IXaWT or
      IXaNP. Interaction of each activated mutant with an active site probe, p
      aminobenzamidine, was also examined; the Kd of interaction in the absence and
      presence (in parentheses) of Ca2+ was: IXaNP or IXaWT 230 microM (78 microM),
      IXaE235K 150 microM (145 microM), IXaE245V 225 microM (240 microM), and autolysis
      loop cleaved IXaE245V 330 microM (350 microM). Next, we evaluated the apparent Kd
      (Kd,app) of interaction of each activated mutant with factor VIIIa. We first
      investigated the EC50 of interaction of IXaNP as well as of IXaWT with factor
      VIIIa in the presence and absence of phospholipid (PL) and varying concentrations
      of factor X. At each factor X concentration and constant factor VIIIa, EC50 was
      the free IXaNP or IXaWT concentration that yielded a half-maximal rate of factor
      Xa generation. EC50 values for IXaNP and IXaWT were similar and are as follows:
      PL-minus/X-minus (extrapolated), 2.8 microM; PL-minus/X-saturating, 0.25 microM;
      PLplus/X-minus, 1.6 nM; and PL-plus/X-saturating, 0.09 nM. Further, Kd,app of
      binding of active site-blocked factor IXa to factor VIIIa was calculated from its
      ability to inhibit IXaWT in the Tenase assay. Kd,app values in the absence and
      presence (in parentheses) of PL were: IXaNP or IXaWT, 0. 19 microM (0.07 nM);
      IXaE235K, 0.68 microM (0.26 nM); IXaE245V, 2.5 microM (1.35 nM); and autolysis
      loop-cleaved IXaE245V, 15.6 microM (14.3 nM). We conclude that (a) PL increases
      the apparent affinity of factor IXa for factor VIIIa approximately 2,000-fold,
      and the substrate, factor X, increases this affinity approximately 10-15-fold;
      (b) the protease domain Ca2+ binding site increases this affinity approximately
      15-fold, and lysine at position 235 only partly substitutes for Ca2+; (c) Ca2+
      binding to the protease domain increases the S1 reactivity approximately 3-fold
      and prevents proteolysis in the autolysis loop; and (d) proteolysis in the
      autolysis loop leads to a loss of catalytic efficiency with retention of S1
      binding site and a further approximately 8-fold reduction in affinity of factor
      IXa for factor VIIIa.

PMID- 9287358
TI  - The H3/H4 tetramer blocks transcript elongation by RNA polymerase II in vitro.
AB  - We have investigated transcript elongation efficiency by RNA polymerase II on
      chromatin templates in vitro. Circular plasmid DNAs bearing purified RNA
      polymerase II transcription complexes were assembled into nucleosomes using
      purified histones and transient exposure to high salt, followed by dilution and
      dialysis. This approach resulted in nucleosome assembly beginning immediately
      downstream of the transcription complexes. RNA polymerases on these nucleosomal
      templates could extend their 15- or 35-nucleotide nascent RNAs by only about 10
      nucleotides in 15 min, even in the presence of elongation factors TFIIF and SII.
      Efficient transcript elongation did occur upon dissociation of nucleosomes with
      1% sarkosyl, indicating that the RNA polymerases were not damaged by the high
      salt reconstitution procedure. Since the elongation complexes were released by
      sarkosyl but not by SII, these complexes apparently did not enter the arrested
      conformation when they encountered nucleosomes. Surprisingly, elongation was no
      more efficient on nucleosomal templates reconstituted only with H3/H4 tetramers,
      even in the presence of elongation factors and/or competitor DNA at high
      concentration. Thus, in a purified system lacking nucleosome remodeling factors,
      not only the core histone octamer but also the H3/H4 tetramer provide an nearly
      absolute block to transcript elongation by RNA polymerase II, even in the
      presence of elongation factors.

PMID- 9287359
TI  - Hypoxia induces c-fos transcription via a mitogen-activated protein kinase
      dependent pathway.
AB  - Hypoxia is a pathophysiological condition that occurs during injury, ischemia,
      and stroke. It is characterized by a decrease of reactive oxygen intermediates
      and a change of the intracellular redox level. In tumors hypoxia is regarded as a
      trigger for enhanced growth and metastasis. Here we report that in HeLa cells,
      hypoxic conditions induce the transcriptional activation of c-fos transcription
      via the serum response element. Mutations in the binding site for the ternary
      complex factor Elk-1 and the serum response factor abolished this induction,
      indicating that a ternary complex at the serum response element is necessary for
      the induction of the c-fos gene under hypoxia. The transcription factor Elk-1 was
      covalently modified by phosphorylation in response to hypoxia. Furthermore this
      hyperphosphorylation of Elk-1, the activation of mitogen-activated protein kinase
      (MAPK), and the induction of c-fos transcripts were blocked by PD98059, a
      specific inhibitor of mitogen-activated protein kinase kinase/extracellular
      signal-regulated protein kinase kinase 1. An in vitro kinase assay with Elk-1 as
      substrate showed that MAPK is activated under hypoxia. The activation of MAPK
      corresponds temporally with the phosphorylation and activation of Elk-1. Thus, a
      decrease of the intracellular reactive oxygen intermediate level by hypoxia
      induces c-fos via the MAPK pathway. These results suggest that the intracellular
      redox levels may be directly coupled to tumor growth, invasion, and metastasis
      via Elk-1-dependent induction of c-Fos controlled genes.

PMID- 9287360
TI  - Isolation and identification of a plasmatocyte-spreading peptide from the
      hemolymph of the lepidopteran insect Pseudoplusia includens.
AB  - Insect blood cells (hemocytes) play an essential role in defense against
      parasites and other pathogenic organisms that infect insects. A key class of
      hemocytes involved in insect cellular immunity is plasmatocytes. Here we describe
      the isolation and identification of a peptide from the moth Pseudoplusia
      includens that mediates the spreading of plasmatocytes to foreign surfaces. This
      peptide, designated plasmatocyte-spreading peptide (PSP1), contains 23 amino acid
      residues in the following sequence: H-ENFNGGCLAGYMRTADGRCKPTF-OH. In vitro assays
      using the synthetic peptide at concentrations >/=2 nM induced plasmatocytes from
      P. includens to spread on the surface of culture dishes. Injection of this
      peptide into P. includens larvae caused a transient depletion of plasmatocytes
      from circulation. Labeling studies indicated that this peptide induced 75% of
      plasmatocytes that were double-labeled by the monoclonal antibodies 49G3A3 and
      43E9A8 to spread, whereas plasma induced significantly more plasmatocytes to
      spread. This suggests that only a certain subpopulation of plasmatocytes responds
      to the peptide and that other peptidyl factors mediate plasmatocyte adhesion
      responses.

PMID- 9287361
TI  - Chemotactic peptide-induced activation of Ras in human neutrophils is associated
      with inhibition of p120-GAP activity.
AB  - The monomeric G-protein Ras is now considered to function as an initial regulator
      of multiple signaling pathways in both normal and transformed cell types.
      Adhesion and chemoattractant receptors are known to trigger activation of Ras in
      human neutrophils, but the signaling mechanism that activates Ras has only been
      partially elucidated. The present results show that in neutrophils, a time- and
      dose-dependent f-Met-Leu-Phe (FMLP)-induced activation of Ras is mediated by Gi2
      proteins, because such activation is inhibited by pertussis toxin and because
      direct stimulation of heterotrimeric G-proteins with AlF4- is sufficient to
      activate Ras. Pretreatment of neutrophils with tyrosine kinase inhibitors, i.e.
      genistein or erbstatin that completely block FMLP-stimulated protein tyrosine
      phosphorylations, did not affect the FMLP-induced activation of Ras. Moreover,
      FMLP did not induce any detectable translocation of Grb2 and Sos to the plasma
      membrane of neutrophils. Other signaling molecules, such as protein kinase C,
      phosphatidylinositol 3-kinase and Ca2+, do not appear to be involved in the FMLP
      induced Ras activation. Instead, stimulation of neutrophils with FMLP or C5a, the
      latter of which also activates Gi2-proteins, resulted in transient inhibition of
      the activity of Ras GTPase-activating proteins (GAP) with kinetics that
      correlated well with the kinetics of Ras activation. Moreover, decreased Ras-GAP
      activity was found in p120-GAP but not in neurofibromin immunoprecipitates of
      FMLP-stimulated cells. These results suggest that tyrosine kinase-dependent Ras
      exchange factors do not contribute to the FMLP-induced activation of Ras but that
      such activation is mediated via inhibition of p120-GAP in neutrophils.

PMID- 9287363
TI  - Recent nutritional approaches to the prevention and therapy of cardiovascular
      disease.
AB  - Nutritional factors play an important role in the development and treatment of
      cardiovascular disease (CVD). However, health care professionals may overlook, or
      even disregard, some of these factors for several reasons, including inadequate
      training and conflicting reports in the biomedical literature. This review
      provides a synopsis of more than two-dozen nutritional approaches to primary and
      secondary prevention and therapy of CVD. Favorable cardiovascular effects have
      been reported with the use of unsaturated fatty acids, vegetarian and semi
      vegetarian diets, dietary fiber, plant sterols, alcoholic beverages, vitamins
      (niacin, E, C, B6, B12, folate), minerals (potassium, calcium, magnesium,
      selenium), conditionally-essential nutrients (coenzyme Q10, L-carnitine, taurine)
      and botanical agents (garlic, hawthorn, gugulipid). In contrast, trans-fatty
      acids, oxysterols, homocysteinemia, carbohydrate intolerance, and excessive
      sodium chloride and iron have been associated with undesirable cardiovascular
      effects. A nutritional approach to CVD provides a pivotal adjuvant to traditional
      pharmaceutical and/or surgical interventions by maximizing the likelihood of
      success in decreasing CVD morbidity and mortality and minimizing the economic and
      social costs associated with this disease.

PMID- 9287364
TI  - A guide to successfully recruiting patients for cardiovascular clinical trials.
AB  - To maximize enrollment in clinical trials, an efficient mechanism for screening
      and recruitment is needed. A national referral center for the treatment of heart
      disease developed a mechanism to maximize patient enrollment in more than 20
      clinical trials simultaneously with a cardiac catheterization laboratory. It
      consists of four primary components: preparation, screening and recruitment,
      evaluation and problem-solving, and communication. This paper describes these
      components and presents information that may be useful in the recruitment of
      patients for clinical trials. It also provides tools that can be adapted and used
      to screen patients for trial eligibility.

PMID- 9287362
TI  - Inhibitory tyrosine protein kinase p50csk is associated with protein-tyrosine
      phosphatase PTP-PEST in hemopoietic and non-hemopoietic cells.
AB  - p50(csk) is a cytosolic tyrosine protein kinase expressed in all cell types.
      Accumulating data show that it inhibits multiple cellular processes, as a
      consequence of its ability to repress the enzymatic activity of Src family
      tyrosine protein kinases. We previously demonstrated that, via its Src homology 3
      (SH3) domain, Csk is tightly bound to PEP, a protein-tyrosine phosphatase (PTP)
      exclusively expressed in hemopoietic cells. In this report, we have tested the
      possibility that Csk also interacts with PTP-PEST, a ubiquitous PTP sharing
      structural homology with PEP. Our studies revealed that Csk was associated with
      PTP-PEST in a variety of cell types, including non-hemopoietic cells. This
      interaction involved the SH3 region of p50(csk) and a proline-rich region
      (PPPLPERTPESFVLADM) outside the catalytic region of PTP-PEST. Even though both
      PTP-PEST and PEP were associated with Csk, significant differences were noted
      between these two PTPs. PTP-PEST, but not PEP, was also complexed with Shc, an
      adaptor molecule implicated in the Ras pathway. Moreover, PTP-PEST and PEP were
      found to accumulate primarily in distinct intracellular compartments in cell
      fractionation studies. In combination, these findings indicated that, like PEP,
      PTP-PEST is probably involved in Csk-mediated functions in mammalian cells.
      Moreover, they suggested that the roles of Csk-PTP-PEST and Csk-PEP are likely to
      be different.

PMID- 9287365
TI  - Antiarrhythmic drug therapy--Part IV: Ventricular arrhythmias.

PMID- 9287366
TI  - Do you have nursing professional liability insurance?--Part II.

PMID- 9287367
TI  - An unexpected ST segment deviation during an exercise treadmill test.

PMID- 9287368
TI  - Strategies for successful reimbursement for investigational circulatory support.

PMID- 9287369
TI  - Activation of left posterior cingulate gyrus by the auditory presentation of
      threat-related words: an fMRI study.
AB  - This study investigated the cortical response to hearing threat-related and
      neutral words using functional magnetic resonance imaging (fMRI) in 16 coronal
      planes. Right-handed volunteers listened to (i) neutral words alternating with no
      words as the control condition, and (ii) neutral words alternating with threat
      related words as the experimental condition. Threat-related words compared to
      neutral words activated left posterior cingulate gyrus in eight of 10 subjects
      with activation most prominent in the retrosplenial region. Patterns of
      activation produced by neutral words compared to no words included bilateral
      temporal and frontal regions but not posterior cingulate. The retrosplenial
      cingulate region has recently been implicated in episodic memory processes. We
      discuss the possible role of the posterior cingulate cortex in processes
      involving emotion and memory and in anxiety disorders.

PMID- 9287370
TI  - A method to determine activation thresholds in fMRI paradigms.
AB  - Determining meaningful activation thresholds in functional magnetic resonance
      imaging (fMRI) paradigms is complicated by several factors. These include the
      time-series nature of the data, the influence of physiological rhythms (e.g.
      respiration) and vacillations introduced by the experimental design (e.g.
      cueing). We present an empirical threshold for each subject and each fMRI
      experiment that takes these factors into account. The method requires an
      additional fMRI data set as similar to the experimental paradigm as possible
      without dichotomously varying the experimental task of interest. A letter fluency
      task was used to illustrate this method. This technique differs from classical
      methods since the Pearson correlation probability values tabulated from
      statistical theory are not used. Rather each subject defines his or her own set
      of threshold probability values for correlations. It is against these empirical
      thresholds, not Pearson's, that an experimental fMRI correlation is assessed.

PMID- 9287371
TI  - Measurement of frontal lobe volume on magnetic resonance imaging scans.
AB  - This article describes rules for measurement of the frontal lobe on thin SPGR
      (spoiled gradient recalled echo in steady state) MRI (magnetic resonance imaging)
      scans. Measurements were performed using a locally-developed software program
      that allows 3-dimensional reconstruction of images, 'painting' of landmarks on
      the surface of the brain, and reconstruction of 2-dimensional images in any plane
      with landmark 'paint' remaining on the surface of the brain. Excellent inter
      rater reliability has been achieved for this method. The approach may be
      particularly useful for studies involving groups of patients whose brains are
      known to be dysmorphic and who may not, therefore, be appropriate for measurement
      methods that involve image warping or dependence on arbitrary landmarks for
      defining the posterior boundary of the frontal lobe.

PMID- 9287372
TI  - Reliability and validity of MRI measurement of the amygdala and hippocampus in
      children with fragile X syndrome.
AB  - Evidence from numerous structural magnetic resonance imaging (MRI) studies has
      converged to implicate mesial temporal lobe structures in the pathophysiology of
      several developmental and psychiatric disorders. Efforts to integrate the results
      of these studies are challenged, however, by the lack of consistency, detail and
      precision in published protocols for the manual measurement of the amygdala and
      hippocampus. In this study, we describe a highly detailed, standardized protocol
      for measuring the amygdala and the hippocampus. Within the context of this
      protocol, we tested the inter- and intra-rater reliability of two frequently
      cited methods for normalizing the anatomical position of the amygdala and
      hippocampus prior to measurement. One method consisted of creating a coronal data
      set in which images are rotated in a plane perpendicular to the long axis of the
      hippocampus. The second method consisted of creating a coronal data set in which
      images are rotated in a plane perpendicular to the axis connecting the anterior
      and posterior commissures. Inter- and intra-rater reliability coefficients (using
      the intraclass correlation) ranged from 0.80 to 0.98, indicating that both
      methods for positional normalization are highly reliable. In addition, we tested
      the validity of each method by comparing the temporal lobe anatomy of children
      with fragile X syndrome to a group of unaffected children matched by age and
      gender. We found that hippocampal volumes in children with fragile X were
      significantly increased when either rotational method was used. These results
      replicated previous findings, suggesting that either method can be validly
      applied to neuronanatomic studies of pediatric populations.

PMID- 9287373
TI  - Altered distribution of parvalbumin-immunoreactive local circuit neurons in the
      anterior cingulate cortex of schizophrenic patients.
AB  - Several lines of evidence support an involvement of the anterior cingulate cortex
      in the pathophysiology of schizophrenia. Immunocytochemical techniques using
      antibodies against calcium-binding proteins permit a selective demonstration of
      certain subgroups of cortical GABAergic interneurons. The anterior cingulate
      cortex from the brains of schizophrenic patients and control subjects was studied
      with an antibody against parvalbumin. The immunoreactive structures were assessed
      qualitatively and quantitatively. Parvalbumin immunoreactivity was detected in a
      subpopulation of GABAergic local circuit neurons, in axonal structures (including
      axon cartridges) and in diffuse, band-like neuropil material. Schizophrenic
      anterior cingulate cortex was found to contain the same interneuron types as
      controls, but displayed a significant increase of parvalbumin-immunoreactive
      neuronal soma profiles in layers Va and Vb, whereas the total neuronal density
      determined in Nissl preparations showed no difference in the two groups. A higher
      density of parvalbumin-positive local circuit neurons may indicate an increased
      inhibition of projection neurons, thus altering the neuronal output pattern of
      the anterior cingulate cortex in schizophrenia.

PMID- 9287374
TI  - The cytokine network in juvenile chronic arthritis.
AB  - This article is an overview of the cytokine network in patients with different
      types of juvenile chronic arthritis. The concept of the production of TH1-cell or
      TH2-cell differentiation as a result of cytokine production and the concept of
      the balance between proinflammatory and anti-inflammatory cytokines are explored.
      The balance of proinflammatory and anti-inflammatory cytokines could be altered
      as a result differences in the expression levels of a number of key cytokines and
      could be the critical events leading to chronic inflammation. Identifying
      molecular targets for intervention therapy to change the balance of the cytokine
      network is proposed.

PMID- 9287375
TI  - Abnormalities in skeletal growth in children with juvenile rheumatoid arthritis.
AB  - A review of the acquisition of peak skeletal mass in normal children and studies
      that have been reported for children with JRA lead to the following tentative
      conclusions: (1) The appendicular skeleton is predominantly the overall status of
      skeletal mineralization; (2) a failure to develop adequate bone mineralization is
      virtually universal in children with JRA and is characterized by a failure of
      bone formation. A failure to undergo the normal increase in bone mass during
      puberty is common in children with JRA and markedly decreases their potential to
      achieve an adequate peak skeletal mass; (3) the onset of accelerated skeletal
      maturation with puberty is a critical period of potential intervention in JRA.
      Conversely, therapeutic interventions later during adolescence offer less promise
      of reversal of inadequate bone mineralization; and (4) the most important
      therapeutic maneuver is likely to be control of the inflammation process,
      although there is hope, at present unsubstantiated, that supplemental dietary
      calcium and vitamin D, and normalization of physical activity, many lead to some
      "catch-up" mineralization.

PMID- 9287376
TI  - Imaging techniques in childhood arthritis.
AB  - Technological advances in imaging have given physicians caring for children with
      arthritis a greater opportunity to detect abnormalities early in the course of a
      disease and better methods for monitoring chronic changes. Indications for using
      radiography, bone densitometry, nuclear medicine, ultrasound, CT scanning, and MR
      imaging are discussed in this article. In this era of managed care, the
      practicing clinician is urged more than ever to consult with the radiologist in
      selecting the study or sequence of studies to be used in particular case. In this
      way, evaluation can be limited to the most effective strategy from both the
      clinical and cost perspectives.

PMID- 9287377
TI  - Acute rheumatic fever. Still a challenge.
AB  - At the end of the 20th century, after an apparent decline, acute rheumatic fever
      (ARF) now constitutes a great challenge for developed and developing countries.
      It is caused by a group A beta-hemolytic Streptococcus upper airways infection,
      but the exact pathogenetic mechanisms are not yet clear. The role of the immune
      system in the pathogenesis of ARF is understood better than genetic host factors.
      ARF can mimic many other diseases, and the diagnosis is based on clinical
      criteria. It is still overdiagnosed and underdiagnosed in different settings.
      Penicillin has greatly contributed to the reduction in the incidence and
      recurrence of this disease. Current schemes of prophylaxis, however, present many
      problems, and failures are common. Future efforts to reduce the burden of this
      disease should induce public health measures the vaccine strategies.

PMID- 9287378
TI  - Juvenile-onset spondyloarthropathies.
AB  - This article discusses the clinical spectrum and characteristics of juvenile
      onset spondyloarthropathies and includes a review of the demographic, clinical,
      radiographic (and other imaging techniques), and laboratory data of conditions,
      syndromes, and diseases making up this group. The pathogenic role of several
      factors in the context of adult-onset patients, but also in regards to studies
      already performed in juvenile-onset patients, is discussed.

PMID- 9287379
TI  - Neonatal lupus erythematosus.
AB  - This article discusses neonatal lupus erythematosus, which is a disease of the
      newborn defined by the presence of maternal autoantibodies and characteristic
      clinical features in the neonatal period. Although the autoantibodies often are
      not associated with clinical disease in the mother, neonatal lupus erythematosus
      is likely the result of fetal or neonatal tissue damage caused by maternally
      transmitted IgG autoantibodies.

PMID- 9287380
TI  - Classification and treatment of the juvenile idiopathic inflammatory myopathies.
AB  - This article reviews the current status of the classification and treatment of
      the juvenile idiopathic inflammatory myopathies. The intent of classification is
      to define homogeneous groups that share similar clinical features, disease
      courses, and responses to therapy. The classification scheme proposed includes
      clinicopathologic subsets, serologic subjects based on the presence of myositis
      specific and myositis-associated autoantibodies, and environmental triggers of
      myositis. Juvenile dermatomyositis is the most common and widely recognized of
      these disorders. The second part reviews the history of treatment of juvenile
      dermatomyositis and discusses agents to consider for patients with refractory
      disease, unacceptable steroid toxicity, or poor prognostic factors.

PMID- 9287381
TI  - Antiphospholipid antibody syndrome in pediatric patients.
AB  - The antiphospholipid antibody syndrome is characterized by the association
      between recurrent arterial or venous thrombosis and the presence of circulating
      antiphospholipid antibodies. Antiphospholipid antibody-related thrombosis seems
      to constitute a significant proportion of childhood thromboses. About one third
      of children suffering a thrombotic event have circulating antiphospholipid
      antibodies, and more than two thirds of children with idiopathic cerebral
      ischemia meet the criteria for the diagnosis of antiphospholipid antibody
      syndrome. Because the other risk factors for thrombosis commonly found in adults
      have no impact on the pediatric patient, the risk for thrombosis and thrombotic
      recurrences and the optimal anticoagulation therapy may differ from adults.

PMID- 9287382
TI  - Infection-related arthritis.
AB  - Postinfection arthritis represents a significant portion of the referrals to
      pediatric rheumatology centers, particularly in the United States. Many viral and
      common bacterial infections can be associated with arthritis, and their
      recognition can sometimes be difficult on a clinical basis. In patients with
      acute onset of arthritis, the clinician should actively seek epidemiologic,
      clinical, or laboratory evidence of infection. Diagnostic tests should be used
      rationally and results interpreted carefully. Some infections, once recognized,
      require antibiotic treatment, but in most cases anti-inflammatory therapy is
      successful in treating articular symptoms.

PMID- 9287383
TI  - Success on the road to adulthood. Issues and hurdles for adolescents with
      disabilities.
AB  - Outcome data from children with connective tissue disease or other disabilities
      and how they function in adulthood continue to underscore the need for transition
      planning. This article addresses the components of transition and the barriers to
      its accomplishment along with the special issues adolescents with disabilities
      face in attaining the developmental tasks along the road to adulthood. Health
      care professionals can be catalyst in the transition process in their role as a
      consultant to young persons with disabilities and their families. It can be
      rewarding and challenging to be a catalyst for a successful transition process
      that results in a happy, meaningful life as an adult with a disability.

PMID- 9287384
TI  - Syndromes and arthritis.
AB  - There are many questions and no clear answers raised by these children. These
      syndromes, however, seem to be biologic experiments of nature and present unique
      opportunities to study the various elements involved in the pathogenesis of
      arthritis. Pediatric rheumatologists are in a unique position to study these
      syndromes.

PMID- 9287385
TI  - Chronic pain states: pathophysiology and medical therapy.
AB  - OBJECTIVE: The pathophysiology and management of chronic pain are reviewed in
      this two-part article, with an emphasis on pharmacological therapies and surgical
      interventions. DATA SOURCES: A thorough literature review of published articles
      available in Medline from 1966 to 1996 on the topic of pain management, including
      diagnosis, pathophysiology, interventions, and treatment. CONCLUSIONS: Despite
      the development of new instruments and treatments to assess and manage pain,
      chronic pain is often poorly understood and inadequately addressed. Caregivers
      often lack sufficient skills to intervene promptly and effectively.
      Traditionally, drug therapy has relied on the nonsteroidal antiinflammatory drugs
      (NSAIDs) and opioid analgesics for chronic nociceptive pain. A newer analgesic
      choice for moderate to moderately severe pain is tramadol, a centrally acting
      agent with at least two complementary mechanisms of action and minimal
      gastrointestinal or renal toxicity. Adjuvant agents, including tricyclic
      antidepressants (TCAs), anticonvulsants, and local anesthetics, also help manage
      chronic neuropathic pain. Although significant advances in the understanding of
      chronic pain and its pathophysiological mechanisms and newer techniques
      (noninvasive and invasive) for chronic pain management have become available,
      reduced patient morbidity and improved quality of life may only be realized with
      an improved understanding of available resources.

PMID- 9287386
TI  - Outcome of renal transplantation in systemic lupus erythematosus.
AB  - OBJECTIVES: (1) To provide an overview of the world's experience with renal
      transplantation in systemic lupus erythematosus (SLE), and to consider the most
      important studies in detail. (2) To examine four specific questions raised by the
      review, including (a) the frequency of recurrent lupus glomerulonephritis (GN);
      (b) the effect of pretransplantation dialysis on transplantation outcome; (c) the
      method of monitoring lupus activity in transplant patients; and (d) the frequency
      of early graft loss among lupus patients. METHODS: We performed a MEDLINE search
      of the world's literature from 1975 to 1997 on the subject of renal
      transplantation in SLE, using the search terms "lupus," "SLE," "kidney," "renal
      transplantation," and "outcome." We included in this review 20 original reports
      that devoted significant attention to the outcome of renal transplantation among
      patients with lupus. RESULTS: Of the nine studies that compared the
      transplantation outcomes of lupus patients with those of transplant patients with
      other causes of end-stage renal disease, the allograft survival rates were
      superior in the comparison groups in six, and approximately equivalent in three.
      The 1-year allograft survival rate of lupus patients with cadaveric renal
      transplants (CRTs) was 67% in the largest multicenter study, significantly lower
      than the rate for the other 14 diseases examined (77%; P = .009). In most
      studies, the lupus groups were significantly younger than their comparison
      groups, but they frequently included larger percentages of black patients. Lupus
      patients who received living-related renal transplants (LRRTs) generally had
      superior graft survival rates compared with those who received CRTs. In the
      largest single-center report, the 5-year graft survival rate in the cyclosporine
      era was 89% for LRRTs, compared with 41% for CRTs. Recurrence of lupus nephritis
      in the allograft is relatively rare, approximately 2%; this estimate is probably
      low. However, recurrent lupus glomerular nephritis (GN) did not invariably result
      in allograft failure. Short length of pretransplantation dialysis (i.e., less
      than 6 months) had no adverse effect on transplantation outcome in 10 of 11
      studies that examined the relationship. Pretransplantation serological
      parameters, such as complement and anti-double-stranded DNA antibody levels,
      appear to be unreliable predictors of the likelihood of recurrence, and also may
      be inaccurate measures of disease activity in the posttransplantation period.
      Finally, 9 of the 20 studies reviewed noted an increased risk of early graft loss
      among lupus transplant patients, possibly because of an increased frequency of
      acute injection reactions and thrombotic events associated with antiphospholipid
      antibodies. CONCLUSIONS: Despite the fact that many lupus patients have excellent
      renal transplantation outcomes, substantial evidence indicates that renal
      transplant patients with lupus do not fare as well as patients with other causes
      of end-stage renal disease. Lupus patients may be particularly susceptible to
      adverse events occurring in the first year after transplantation. Further
      investigation is needed to improve renal transplantation outcomes for patients
      with lupus.

PMID- 9287387
TI  - Valvular dysfunction in antiphospholipid syndrome: prevalence, clinical features,
      and treatment.
AB  - Valvular abnormalities develop in 36% and 35% of patients with primary
      antiphospholipid syndrome (PAPS) and with systemic lupus erythematosus (SLE)
      respectively, and in 48% of patients with SLE and antiphospholipid antibodies
      (aPL). Valvulopathy includes leaflet thickening, vegetations, regurgitation, and
      stenosis. A literature survey shows that significant morbidity from valvular
      dysfunction, mostly mitral regurgitation leading to congestive heart failure,
      occurs in 4% and 6% of SLE and PAPS patients, respectively. The pathogenesis of
      valvulopathy may involve interaction of aPL with antigens on the valve surface,
      resulting in valvulitis. Current therapy includes symptomatic measures and valve
      replacement. A novel approach for symptomatic antiphospholipid syndrome (APS)
      related valvulopathy involves treatment with systemic corticosteroid. We describe
      four such patients and their dramatic clinical and hemodynamic response to
      treatment with prednisone when symptomatic measures failed.

PMID- 9287388
TI  - Therapy with cyclosporine in psoriatic arthritis.
AB  - OBJECTIVE: To evaluate the efficacy and toxicity of cyclosporin A (CsA) in the
      treatment of patients with psoriatic arthritis (PsA). METHODS: We reviewed the
      literature dealing with CsA treatment of PsA. RESULTS: In the 1980s, some studies
      evaluating CsA in severe cases of psoriasis documented an improvement in the
      associated arthritis. Subsequently, open prospective studies included patients
      with active peripheral arthritis. Using initial CsA dose of 3 to 6 mg/kg/day,
      improvement in the clinical parameters was noted. A controlled trial showed that
      CsA and methotrexate (MTX) are equally effective treatment for PsA. CsA and MTX
      combination was effective in PsA patients resistant to previous second-line
      therapy. No studies have evaluated the efficacy of CsA on axial disease and on
      the progression of radiological damage. The most important side effect was
      nephrotoxicity. However, of 170 CsA-treated patients in 16 studies, only 10 (6%)
      discontinued the drug because of renal side effects. CONCLUSIONS: CsA seems to be
      an effective and safe therapy for PsA. However, controlled studies on large
      number of patients are necessary.

PMID- 9287389
TI  - Total joint arthroplasty and the immune response.
AB  - Total joint replacement arthroplasty has proved highly successful in the
      management of osteoarthritis and rheumatoid arthritis. The cause of aseptic
      loosening of prosthetic joint replacement components is unclear. Early experience
      with total joint arthroplasty was plagued by a number of problems that no longer
      exist as major impediments to long-term success. Improvement in the operating
      room environment and the use of prophylactic antibiotics have substantially
      reduced the high incidence of infection to less than 1%. Implant materials have
      long been considered biologically inert, but recent studies indicate that
      inflammatory reactions directed against the implanted materials may contribute to
      aseptic loosening. Currently, particulate debris from cement or polyethylene
      causing loosening of the prosthesis is the major problem in total joint
      arthroplasty. Significant data suggest a progression from a simple inflammatory
      reaction to complex immune responses against the biomaterials. The cellular
      responses to particles of polymethylmethacrylate, ultra-high-molecular-weight
      polyethylene, and alloys of cobalt-chromium and titanium have been assayed in
      vitro in patients with osteoarthritis, rheumatoid arthritis, and avascular
      necrosis who had total joint replacement. Elevated immunologic cell proliferation
      responses to both acrylic and cobalt chromium were observed in patients with
      aseptically loosened prostheses. These findings suggest that the development of a
      cellular response to particulate debris may be significant in the pathogenesis of
      aseptic loosening.

PMID- 9287390
TI  - William Osler and development of the concept of systemic lupus erythematosus.
AB  - OBJECTIVE: This historical review summarizes the understanding of lupus
      erythematosus (LE) during the time of the career of William Osler and analyzes
      factors that may have retarded the clinical identification of this disease.
      METHODS: All of Osler's writings related to diseases that he defined as the
      "erythema group" were studied, in conjunction with relevant writings on Schonlein
      Henoch purpura and erythema multiforme. RESULTS: Osler did not knowingly describe
      cases of LE, nor did he discuss the disease in general. He proposed that a
      primary skin disease, which in some cases has visceral manifestations, may
      develop as a purely visceral disease, using cases from his "erythema group"
      cohort as evidence. CONCLUSIONS: The reluctance into the 1940s to diagnose
      systemic LE was primarily a consequence of the erroneous belief that a skin
      eruption was required to establish the diagnosis. Osler's teaching the possible
      dissociation of visceral from cutaneous symptoms with regard to the erythema
      group was not analogized to LE. The interpretation that Osler had elucidated
      aspects of LE has developed since 1937 and attributes insights to Osler that his
      writings do not substantiate.

PMID- 9287392
TI  - Immunological gene therapy approaches for malignant melanoma. 2. Preclinical
      studies and clinical strategies.
AB  - Immuno-gene therapy approaches for the treatment of malignant melanoma are
      categorized into two major subgroups according to an active or passive
      immunological principle. Active immuno-gene therapy is subdivided into melanoma
      cell vaccines, DNA-based vaccinations and the treatment of pre-existing tumor
      tissue by cell-mediated or direct transfer of cytokine and/or cell surface signal
      genes. Passive immuno-gene therapy, employing an adoptive treatment with in vitro
      activated and expanded anti-tumor effector cells, involves two major application
      fields for gene transfer techniques, first the genetic modification of the
      effector cells, and second the in vivo amplification of pre-effector cells by
      procedures also used in active immuno-gene therapy. Corresponding preclinical
      studies are reviewed. The clinical studies inaugurated during the last few years
      are mostly still ongoing and focus on treatment safety and tolerability rather
      than efficacy. A recent trend is emerging to explore recombinant adenovirus and
      vaccinia virus vectors particularly with regard to in vivo gene transfer
      applications. Overall, immuno-gene therapy of melanoma is still in a highly
      experimental stage of development but may become a safe, efficacious and
      practical adjuvant treatment modality in the future.

PMID- 9287391
TI  - An historical review of rheumatoid arthritis treatment: 1948 to 1952.
AB  - OBJECTIVES: The early responses by practicing physicians to the discovery of the
      effect of cortisone (compound E) and adrenocorticotropic hormone (ACTH) on acute
      rheumatoid arthritis in 1948 and their reactions to the drugs' scarcity have been
      reviewed. METHODS: Review of the relevant literature in American, British, and
      European medical journals and some newspapers. RESULTS: Whereas the effect of the
      compound E and ACTH was stunning, their scarcity made them unavailable to most
      physicians. Nevertheless, practicing physicians took a lively interest in the new
      therapy, as witnessed by the large number of letters with comments and questions
      to professional journals from all over the world. As expected, most of these were
      about attempts to find a substitute for cortisone or a way to release it
      endogenously to a sufficient degree. A few alternative therapies were suggested
      too, some quite unorthodox. A lively interest was shown by the general public.
      CONCLUSIONS: No alternative therapy recommended to treat acute rheumatoid
      arthritis in lieu of cortisone proved to be effective. The era of scarcity was
      ended by the discovery of a more efficient method to manufacture cortisone.

PMID- 9287393
TI  - Sebaceous-gland deposition of isotretinoin after topical application: an in vitro
      study using human facial skin.
AB  - As yet, topically applied isotretinoin fails to show convincing clinical efficacy
      in the treatment of severe recalcitrant acne. Although the reason for this is not
      known, it is possible that topical application results in low, pharmacologically
      inactive isotretinoin concentrations in the sebaceous glands, the most likely
      site of isotretinoin action. It has been suggested that topically applied
      liposomes enhance the delivery of drugs into the sebaceous glands. Accordingly,
      we compared the isotretinoin concentration in sebaceous glands and other skin
      compartments following topical application of small unilamellar vesicles,
      multilamellar vesicles, preformed vesicles (Natipide II) or mixed micelles of
      lecithin and bile salt. We found that the concentration of isotretinoin measured
      in the sebaceous glands varied between 0.17 and 1.57 ng/mg tissue. The comparison
      between ethanolic gel and liposomal or micellar gel did not reveal any
      significant difference. However, application of the Natipide formulation resulted
      in significantly lower isotretinoin concentrations in the sebaceous glands when
      compared to the ethanolic gel. Autoradiography and fluorescence microscopy
      indicated that isotretinoin penetrated the sebaceous glands along the follicular
      route. In conclusion, our in vitro study showed that, following topical
      administration, substantial amounts of isotretinoin were delivered to the
      sebaceous glands via the follicular route, whereby the ethanolic gel was as
      efficient as a liposomal or a mixed micellar gel.

PMID- 9287394
TI  - DNA ploidy changes in rhino mouse skin induced by all-trans retinoic acid and
      retinol.
AB  - OBJECTIVE: In order to assess the proliferative changes induced by all-trans
      retinoic acid (RA) and retinol (ROL), we have carried out a study of the DNA
      content of basal and suprabasal keratinocytes after epicutaneous application on
      the rhino mouse. STUDY DESIGN: Skin sections were analyzed stereologically and
      cytophotometrically using the Feulgen technique. The diploid DNA value (2C) was
      obtained from hepatocyte nuclei of control animals. Whereas cells in phase G0-G1
      will show a 2C content, cells during phase S and in phase G2-M will show DNA
      values ranging from 2C to 4C and 4C, respectively. RESULTS: Although epidermal
      thickness (ET) increased significantly in all treated animals, surface density
      only increased in animals treated with all-trans RA. Quantification of DNA
      content of basal keratinocytes showed reduction of 2C and 2C-4C populations with
      a commensurate increase in proportions of cells with 4C and > 4C in the animals
      treated with 0.025% all-trans RA and ROL. Suprabasal keratinocytes of mice
      treated with 0.025% all-trans showed a decrease of the 2C population and an
      increased proportion of cells with 4C. Whereas 0.025% all-trans RA induced an
      increase of both basal and suprabasal DNA indices, ROL enhanced only the basal
      DNA index significantly. CONCLUSION: Animals treated with 0.025% ROL showed a
      significant increase in the basal proliferative index (PI) while the suprabasal
      PI remained constant; treatment with 0.025% all-trans RA produced a significant
      increase of both basal and suprabasal PIs and parakeratotic hyperkeratosis
      probably due to incomplete differentiation.

PMID- 9287395
TI  - Effects of vitamin D3 on keratinocyte proliferation and differentiation in vitro:
      modulation by ligands for retinoic acid and retinoid X receptors.
AB  - Keratinocytes express receptors for 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], all
      trans-retinoic acid (all-trans-RA), 9-cis-retinoic acid (9-cis-RA) and
      triiodothyronine (T3). The vitamin-D receptor (VDR) can act as a transcription
      factor by forming homodimers or heterodimers with the retinoic-acid receptor
      (RAR), the retinoid X receptor (RXR) or the triiodothyronine receptor (TR). This
      study investigated whether the antiproliferative and prodifferentiating effects
      of 1,25(OH)2D3 on normal human keratinocyte cultures is modified by all-trans-RA,
      a ligand for RAR, by CD2809, a ligand for RXR, by 9-cis-RA, a ligand for the RAR
      and RXR, and T3, a ligand for the TR. Submerged, second-passage normal human
      keratinocytes were grown to approximately 30% confluency before incubation for 4
      days with ligands in keratinocyte growth medium supplemented with 3% charcoal
      stripped fetal calf serum and 0.3 mM Ca2+. Proliferation was measured by the
      dimethylthiazolyl-diphenyl-tetrazolium-bromide assay. Then differentiation was
      determined in the same culture, performing a cell ELISA for transglutaminase type
      1. All-trans-RA, 9-cis-RA and CD2809 had a slight stimulatory effect on
      proliferation. In combination with 1,25(OH)2D3, all retinoids partially
      counteracted the antiproliferative effect of 1,25(OH)2D3. The differentiation was
      dose-dependently inhibited by all-trans-RA, 9-cis-RA and CD2809 alone. In
      combination with 1,25(OH)2D3, all retinoids reversed the prodifferentiating
      effect of 1,25(OH)2D3, resulting in a net inhibition of differentiation. T3 had
      no effect on proliferation of differentiation, either alone or in combination
      with 1,25(OH)2D3. In conclusion, retinoids with different receptor selectivities
      had similar effects on keratinocyte proliferation and differentiation. The
      effects of 1,25(OH)2D3 on proliferation and differentiation were reversed by all
      retinoids. Therefore ligand-dependent heterodimer formation between the VDR and
      retinoid receptors may not be important for the combined effects of 1,25(OH)2D3
      and retinoids on keratinocyte proliferation and differentiation in vitro.

PMID- 9287396
TI  - Effects of ethyl alpha-D-glucoside on skin barrier disruption.
AB  - Daily treatments of skin in hairless mice with concentrates of rice wine,
      Japanese traditional alcohol, lowered transepidermal water loss levels compared
      to the controls on the 3rd day after ultraviolet B (UVB) irradiation. These
      findings indicate that the concentrates of rice wine suppress the murine skin
      barrier disruption caused by UVB. Ethyl alpha-D-glucoside (alpha-ethylglucoside),
      one of the peculiar components in rice wine, showed the same effect, whereas beta
      ethylglucoside had no effect. In order to clarify the functions of alpha
      ethylglucoside on murine skin, we examined the effects of this compound on the
      expression of some phenotypes in human keratinocytes in vitro. As a result, alpha
      ethylglucoside as well as beta-ethylglucoside enhanced cell proliferation weakly,
      and the formation of cornified envelopes and differentiated type keratin (K1) in
      keratinocytes was accelerated by alpha-ethylglucoside but not by beta
      ethylglucoside. From the results, we conclude that alpha-ethylglucoside enhanced
      the differentiation of keratinocytes, which might be related to reduced barrier
      disruption by UVB.

PMID- 9287398
TI  - Prevention of graft rejection and graft-versus-host reaction by a novel
      immunosuppressant, FTY720, in rat small bowel transplantation.
AB  - In the present study, we examined the immunosuppressive effect of a new drug,
      FTY720, on small bowel transplantation (SBT) in rats. Grafts from (LEW x BN) F1
      to-LEW rats treated with FTY720 at 0.5 mg/kg from day 0 to 14 post-SBT survived
      significantly longer than untreated grafts. In addition, the administration of
      FTY720 combined with cyclosporin (CyA; 5 mg/kg per day) had a synergistic effect
      on allograft survival. The graft-versus-host reaction (GVHR) that occurred in the
      LEW-to-F1 rats was markedly reduced after the administration of FTY720. FTY720
      combined with a low dose of CyA completely abrogated GVHR without any adverse
      reaction. FTY720 treatment resulted in a significant decrease in the number of
      lymphocytes in the peripheral blood and the spleen, but the number of peripheral
      neutrophils was unchanged. Thus, FTY720 would appear to be an ideal drug to
      combine with CyA in order to control the immune reaction after SBT.

PMID- 9287397
TI  - Activity and inhibition of 3-beta-hydroxysteroid dehydrogenase/delta-5-4
      isomerase in human skin.
AB  - Activity and inhibition of 3 beta-hydroxysteroid dehydrogenase/delta 5-4
      isomerase, a key example of biosynthesis of androgenic steroids, in human skin
      were studied. Whole-width dermal tissue specimens excised from various regions of
      the male and female body were investigated with an in vitro radioenzyme assay
      method using dehydroepiandrosterone as substrate. The Michaelis-Menten constant
      of the enzyme was found to be Km = 10nM and the maximal velocity was Vmax = 0.625
      pmol produced 4-androstene-3,17-dione/mg protein/20 min. Activity of 3 beta
      hydroxysteroid dehydrogenase/delta 5-4-isomerase in male inguinal skin (n = 8)
      was 0.132-0.412, in female abdominal skin (n = 4) 0.140-0.255, in perineal skin
      (n = 4) 0.138-0.962 pmol/mg protein/20 min. The synthetic steroids cyproterone
      acetate, 4-MA and epostane proved to be potent inhibitors, IC50 values were 150,
      6.2 and 1.45 nM, respectively.

PMID- 9287399
TI  - The characterization of reconstituted passenger leukocytes on the induction of
      tolerance in rat liver transplantation.
AB  - The tolerance induced by orthotopic liver transplantation [DA (RT1a) rats to PVG
      (RT1c) rats] can be prevented by total body irradiation of the donor rat.
      Reconstitution of the irradiated donor with DA splenic leukocytes reintroduces
      this tolerance. To investigate the major histocompatibility complex (MHC)
      specificity of passenger leukocytes, irradiated DA donors were reconstituted by
      third-party BN (RT1n) splenic leukocytes. The reconstitution with BN splenocytes
      re-established DA-specific tolerance in PVG recipients, as confirmed by
      subsequent DA cardiac allografting, while BN hearts were rejected with second-set
      tempo. To determine which cell components play an important role in re
      establishing liver graft tolerance, DA splenic leukocytes were further purified
      into three types: T, B, and adherent cells. Only "T-cell-enriched" preparations
      restored liver graft tolerance in three out of five PVG recipients. These results
      suggest that passenger leukocytes of differing MHC types can help to induce liver
      specific tolerance and that T cells in the liver graft may be essential to
      regulate tolerance induction.

PMID- 9287400
TI  - Comparison of Neoral and Sandimmun for induction and maintenance
      immunosuppression after kidney transplantation.
AB  - We compared the mean trough level/dose (L/D) ratio, mean coefficient of variation
      (CV) of individual patients, and graft, patient, and rejection-free survival
      rates of 40 renal transplant recipients receiving Neoral (CyE) with 103
      consecutive renal transplant recipients receiving Sandimmun (CyA). The mean L/D
      ratio on the 3rd post-transplant day (16.2 vs 11.8, P < 0.04), in the 1st week
      (24.6 vs 16.1; P < 0.03), and 1st month (39.1 vs 28.7; P < 0.05) were higher in
      the CyE group. In both groups the L/D ratio improved in proportion to the
      duration of time post-transplant and reached a maximum in the 3rd post-transplant
      month. In the early post-transplant period in particular, the number of patients
      achieving target levels was significantly higher, and the mean dose needed to
      achieve target levels lower, in the CyE group. The variation in trough levels,
      demonstrated by the CV, was lower in the CyE group (0.41 +/- 0.14) than in the
      CyA group (0.62 +/- 0.21; P < 0.005). Actuarial 1-year patient and graft survival
      rates in the CyE group were 100% and 96%, respectively; these were similar to the
      100% and 95% in the CyA group. The 1-year rejection-free survival rate in the CyE
      group was 61% compared to 43% in the CyA group (P < 0.02). We conclude that it is
      possible to obtain higher blood trough levels at lower doses by administering
      CyE, particularly in the early post-transplant period. The lower variability of
      trough levels and the higher L/D ratio in the CyE group, which are related ti
      improved bioavailability of CyE, may explain the lower rejection rate among these
      patients. In this study, the microemulsion formulation of cyclosporin (CyE) was
      found to be more beneficial and cost-effective as induction and maintenance
      immunosuppression than the conventional formulation (CyA).

PMID- 9287401
TI  - Homologous testis transplantation in dogs.
AB  - There is growing interest in the possible use of homologous testis
      transplantation for the treatment of anorchia and male infertility. In order to
      test the surgical and immunological feasibility of this therapy, three series of
      experimental studies of homologous testis transplantation were carried out in
      dogs. In the first pilot study, four beagles from the same litter were
      transplanted using microsurgical techniques for end-to-end anastomosis of the
      testicular vessels and the vas deferens. These dogs received cyclosporin A (CyA)
      for 3 months after transplantation. The longest functional graft survival in this
      series was 163 days, strongly suggesting that long-term survival of a
      homologously transplanted testis graft is possible. A second series of operations
      was performed on ten mongrel dogs. The same surgical technique was employed and
      the series was divided into three groups. Group 1 received CyA monotherapy, group
      2 a combination of CyA and prednisolone, and group 3 received no
      immunosuppression. The average graft survival time in this series was 28 days,
      significantly less than the 71 days in the first series. The dogs in group 2,
      however, had graft survival times that were three times longer than those in the
      other two groups, suggesting that CyA in combination with prednisolone yields the
      best graft survival. In the third series, five littermates received a testis
      graft after castration. Immunosuppression was achieved by administration of CyA
      and prednisolone for 3 months. In three out of five animals, the graft survived
      until the immunosuppressive therapy was suspended. Histological biopsies of the
      graft 3 months after transplantation showed the same maturation of sperm cells as
      in the control testis of the same dog. The results of the last series suggest
      that long-term survival of homologously transplanted testis grafts in dogs is,
      indeed, possible with the aid of CyA and prednisolone.

PMID- 9287402
TI  - A prospective study on the effect of recipient nutritional status on outcome in
      liver transplantation.
AB  - In a prospective study, we have examined the effect of nutritional status, using
      anthropometric measurements, on outcome in 102 consecutive adult patients
      undergoing elective orthotopic liver transplantation. Mid-arm muscle
      circumference was calculated from these two measurements. Patient outcome
      variables were time spent in the intensive therapy unit, total time in hospital,
      infective complications and mortality within 6 months. Graft outcome variables
      were early graft function, peak aspartate transaminase, alkaline phosphatase,
      bilirubin and prothrombin time. Group A patients were below and group B patients
      above the 25th percentile for mid-arm circumference and triceps skin fold
      thickness. Eighty-four patients (79%) were at or below the 25th percentile of
      anthropometric measurements and 30 patients (28%) were below the 5th percentile.
      The median mid-arm muscle circumference in group A was 22.3 (range 16.4-28.9) cm
      and 25.7 (range 21.7-31.8) cm in group B. The medial albumin level was similar in
      the two groups. There were significantly more bacterial infections in group A
      (27/84, 32%) than in group B (2/22, 8%; chi(2) = 5.4, P = 0.02). There was a
      difference in mortality up to 6 months post-operatively that failed to reach
      statistical significance (Wilcoxon-Gehan statistic -199, P = 0.09). There were
      11/84 (13%) deaths in group A and no deaths in group B (chi(2) = 2.8, P = 0.09).
      Post transplantation, there were significant differences (Kruskal-Wallis Anova)
      between groups A and B for peak alkaline phosphatase (683 vs 334 IU/I, P = 0.05)
      and peak prothrombin time [16 (range 13-25) vs 19.5 (range 12-65), P = 0.03].
      These data suggest that a significant proportion of patients undergoing liver
      transplantation are nutritionally compromised and that this has effects on
      patient infection, susceptibility, graft function and mortality, which may
      possibly be improved by nutritional intervention.

PMID- 9287404
TI  - Cold storage sensitizes hepatocytes to oxidative stress injury.
AB  - Liver cold storage leads to oxygen free radical production and reperfusion
      injury. Antioxidants are effective in suppression reperfusion injury in rat
      livers when used in the reperfusion medium. However, in clinical liver
      transplantation their effectiveness is not clear, which may be due to the way
      they are used (in the recipient). In this study we compare the effectiveness of
      antioxidants when used in the reperfusion medium versus the cold storage solution
      in isolated hepatocytes and the isolated perfused liver. Hepatocytes were cold
      stored in UW solution for 24 h. Oxidative stress, induced by t-butyl
      hydroperoxide (tBHP), was measured in the presence of one of five different
      antioxidants--deferoxamine (DFO), dithiothreitol (DTT), trolox, tocopherol,
      dimethylthiourea (DMTU)--in the reperfusion buffer or UW solution. Efficacy was
      judged by reduction in membrane damage (LDH release) during rewarming. Also, rat
      livers were cold stored for 48 h in UW solution (+/- antioxidant) and reperfused
      (+/- antioxidants). Efficacy was judged by the effect on enzyme release and bile
      production. Cold storage of hepatocytes for 24 h sensitized them to oxidative
      stress. The concentration of tBHP required to induce maximal cell death (80%-90%
      LDH release) was reduced from 1.3 mM (fresh cells) to 0.37 mM (LD-50 values). All
      antioxidants except DMTU suppressed oxyradical-induced LDH release when used in
      the reperfusion medium, but only DFO was effective when used in the UW solution.
      In the isolated perfused liver, DFO, DTT, and trolox were effective and
      suppressed enzyme release when added to the reperfusion buffer, but none were
      effective when used in the UW solution. We conclude that cold storage sensitizes
      liver cells to oxidative stress. The most effective antioxidant was the iron
      chealator, DFO, which was effective in the reperfusion buffer (isolated perfused
      sliver or hepatocytes) but not in the UW solution when tested in the isolated
      perfused liver. Suppression of reperfusion injury in liver transplantation could
      be obtained by antioxidant therapy. However, it is unclear how best to deliver
      the antioxidants to the site of oxyradical generation.

PMID- 9287403
TI  - Prophylaxis of acute gastroduodenal bleeding after renal transplantation.
AB  - Severe gastroduodenal bleeding after renal transplantation is effectively
      prevented by H2 receptor blockers. New drugs for prophylaxis include proton pump
      inhibitors. The aim of the present study was to compare the effects of
      prophylaxis with the H2 blocker ranitidine and with the proton pump inhibitor
      omeprazole. One hundred seventy-seven consecutive patients were included in a
      controlled, prospective, randomized study after cadaveric renal transplantation.
      In one case, ranitidine failed to prevent exsanguination due to duodenal peptic
      ulcer bleeding. No bleeding was noted in the omeprazole group. There were no
      significant differences between the groups in hospitalization time, development
      of renal function, amount of cyclosporin A, prednisone, azathioprine, or
      methylprednisoline ingested, or laboratory biochemical parameters. We conclude
      that prophylaxis of severe gastroduodenal bleeding after renal transplantation
      with omeprazole is effective. Omeprazole is certainly as good as ranitidine; its
      advantages are a prolonged effect and a simple dosage, independent of graft
      function development.

PMID- 9287407
TI  - Orthostatic acute renal failure in a renal transplant.
AB  - Complications due to ureteric obstruction are an occasional cause for renal
      transplant dysfunction. Here we report an unusual case of orthostatic renal
      failure in a renal transplant recipient. Our patient had the previously reported
      predisposing risk factors including: female sex, obesity, and lax abdominal
      musculature. It is important to recognize this unusual complication of renal
      transplantation early in order to preserve long-term graft function.

PMID- 9287405
TI  - Integrated intestinal capacity and nutritional status following small bowel
      transplantation.
AB  - Successful small bowel transplantation requires normal functional capacity of the
      graft and unaltered metabolism of the host. Weight gain and wet weight of muscle
      groups and intra-abdominal fat pads were compared between transplanted, sham
      operated, short bowel-operated, and normal rats that were fed either standard
      chow or fat-enriched (15%) pellets. Weight gain and wet weight of muscle groups
      and fat pads for the control, transplanted, and sham-operated rats were
      identical, while short bowel animals showed reduced weight. Transplanted rats
      receiving fat-enriched food had lower wet weight of fat pads than control animals
      on the high-fat diet. We conclude that small bowel transplantation makes it
      possible to overcome the intestinal failure associated with short bowel syndrome,
      leading to overall normal weight gain and development of the recipient. However,
      altered fat metabolism, reflected in changed body composition, was observed in
      transplanted animals on the high-fat diet.

PMID- 9287408
TI  - Conversion from cyclosporin to tacrolimus in a patient with prolonged acute
      tubular necrosis.
AB  - Acute tubular necrosis (ATN) is a common condition of following cadaveric renal
      transplantation with an incidence in many series of nearly 50%. The aetiology is
      uncertain; however, it would appear to be related to damage to the transplant
      kidney either prior to retrieval, During cold preservation or during re-warming
      of the kidney at the time of anastamotic construction. There is no specific
      therapy for ATN and treatment is comprised of an expectant policy with supportive
      dialysis and fluid restriction. Renal function improves in the majority of cases,
      though there may be delayed function for several weeks. We report a case of
      dialysis-dependent ATN that had persisted for 5 months following transplantation.
      Following conversion to tacrolimus there was immediate improvement in renal
      function, and after a month of tacrolimus therapy the patient was dialysis
      independent.

PMID- 9287406
TI  - Renal-splenic shunt for infrahepatic caval occlusion after piggy-back liver
      transplantation.
AB  - Inferior vena cava thrombosis after liver transplantation is uncommon. We
      describe a case of this unusual complication occurring after piggy-back (end-to
      side) graft implantation. Renal failure, lower limb edema, and hemodynamic
      instability were the presenting symptoms requiring immediate surgical correction
      with a left renal-to-splenic vein shunt over a ringed 2.5-cm prosthesis. The
      decision to go ahead with the shunt was preceded by an intraoperative
      confirmation of a 10-cm H2O pressure gradient between the caval and portal
      circulations. This gradient, unlike that observed in liver cirrhosis, ultimately
      turned a splenorenal shunt into a renal-splenic one. Six months after the
      procedure, the patient is alive and well with normal liver and renal function.
      The technique described may be useful in the management of other clinical
      conditions of acute infrahepatic caval hypertension.

PMID- 9287409
TI  - Systemic liberation of interleukin-8 in the perioperative phase of liver
      transplantation.
AB  - Serum levels of interleukin-8 (IL-8) were investigated in the perioperative phase
      of liver transplantation (LTx) in order to help determine whether this cytokine
      might serve as a parameter for preservation injury. In a study of 45 patients
      undergoing LTx, systemic IL-8 was estimated at the end of the anhepatic phase, at
      30, 60, and 120 min after reperfusion of the graft, and 24 h and 7 days after
      LTx. A maximum mean concentration of 665 +/- 135 pg/ml was seen 60 min after LTx.
      The minimum was found on the 1st postoperative day (POD 1): 328 +/- 33 pg/ml.
      Significant changes were found between 60 min and PODs 1 and 7, as well as
      between 120 min and POD 1. Differences in cold ischemia time were not found to be
      significant. We conclude that monitoring of systemic IL-8 levels is not useful in
      the development of new liver preservation concepts.

PMID- 9287410
TI  - Hepatic artery thrombosis as a complication of amputation neuroma of the liver
      graft hilum.

PMID- 9287411
TI  - Extra-anatomic venous graft for portal vein thrombosis in liver transplantation.

PMID- 9287412
TI  - Comparison of old and new IMX assays for monitoring of tacrolimus levels.

PMID- 9287413
TI  - Isolation and structure of the human cancer cell growth inhibitory
      cyclodepsipeptide dolastatin 16.
AB  - An investigation of the sea hare Dolabella auricularia from Papua New Guinea has
      led to discovery of the new cyclodepsipeptide dolastatin 16 (3) containing two
      new amino acid units designated dolamethylleuine (Dml) and dolaphenvaline (Dpv).
      The structural elucidation was achieved by means of high-field (500 MHz) NMR and
      tandem MS/MS mass spectral interpretations and allowed the assignment of cyclo
      (Pro-Dpv-Pro-Dml-O-Lac-Pro-O-Hiv-MeVal). The new depsipeptide exhibited strong
      inhibition of growth against a variety of human cancer cell lines.

PMID- 9287414
TI  - Pyrrolidinooxazolidine alkaloids from two species of ladybird beetles.
AB  - From the mixture of alkaloids obtained from adults of two species of ladybird
      beetles, Epilachna varivestis and Epilachna borealis, a novel bicyclic alkaloid,
      5-(12'-aminotridecyl)pyrrolidinooxazolidine [(5 alpha, 7 a beta)-hexahydro-alpha
      methylpyrrolo[2,1-b]oxazole-5-dodecaneami ne] (2) was characterized on the basis
      of spectrometric and synthetic investigations. This new alkaloid is related
      structurally to a monocyclic congener 1-(2-hydroxyethyl)-2-(12'
      aminotridecyl)pyrrolidine (1), previously characterized from E. varivestis. Two
      additional alkaloids (lower homologs of 1 and 2) from E. borealis were
      characterized as 5-(10'-aminoundecyl)pyrrolidinooxazolidine [(5 alpha,-7 a beta)
      hexahydro-alpha-methylpyrrolo[2,1-b]oxazole-5-decaneamine ] (7) and 1-(2
      hydroxyethyl)-2-(10'-aminoundecyl)pyrrolidine (8), on the basis of their mass
      spectra.

PMID- 9287415
TI  - Flavonoids as inhibitors or enhancers of the cytotoxicity of tumor necrosis
      factor-alpha in L-929 tumor cells.
AB  - The effects of some selected flavonoids on tumor necrosis factor-alpha (TNF)
      induced cytotoxicity in murine fibroblast L-929 cells were studied. All of the
      flavanones tested as well as a flavan, epicatechin, protected L-929 cells from
      TNF-induced cell death of the flavanones tested, hesperetin, isosakuranetin, and
      pinocembrin failed to modify TNF cytotoxicity, but the 3',4'-dihydroxyflavanones,
      eriodictyol and taxifolin, showed a protective effect. Eriodictyol was the most
      potent protective agent of all the flavonoids tested, while a 4'
      hydroxyflavanone, naringenin, rather showed enhancement of TNF cytotoxicity. Of
      the flavones tested, chrysin and apigenin markedly augmented the cytotoxicity of
      TNF, while luteolin showed a weak protective effect. The magnitude of protection
      and potentiation by these flavonoids were concentration-dependent and these
      effects were not altered when the flavonoids were added as much as 2 h after TNF
      treatment.

PMID- 9287416
TI  - Koreoside A, a new nonholostane triterpene glycoside from the sea cucumber
      Cucumaria koraiensis.
AB  - The new triterpene glycoside koreoside A (1) has been isolated from the sea
      cucumber Cucumaria koraiensis. Koreoside A (1) is the first glycoside reported
      from holothurians that presents a delta(7) nonholostane aglycon without a lactone
      group and with a shortened side chain. Its structure has been elucidated by 13C
      and 1H NMR as well as FABMS studies.

PMID- 9287417
TI  - Structure of eximisoside A, a novel triterpene glycoside from the Far-Eastern sea
      cucumber psolus eximius.
AB  - The new triterpene saponin eximisoside A (1) has been isolated from the Far
      Eastern sea cucumber Psolus eximius and its structure elucidated by 1D and 2D NMR
      (13C, 1H, 1H-1H COSY, HMQC, and NOESY spectra), and FABMS studies. The structural
      features of eximisoside A (1) are the rare presence of a 23 double bond in the
      aglycon and the absence of quinovose, typically found in the oligosaccharide
      chain of holothurian glycosides.

PMID- 9287418
TI  - Cembrene A and a congeneric ketone isolated from the paracloacal glands of the
      Chinese alligator (Alligator sinensis).
AB  - A diterpene hydrocarbon and diterpene ketone isolated from the paracloacal gland
      secretions of the Chinese alligator (alligator sinensis) were examined by GC-MS
      and 1H-NMR, 13C-NMR, and IR spectroscopy, and identified as 4,8,12-trimethyl-1-(1
      methylethenyl)-3,7,11-cyclotetradecatrien e (cembrene A, 1) and its congeneric
      ketone, 4,8,12-trimethyl-1-(1-methylethenyl)-3,7-cyclotetradecadien- 10-one (2),
      respectively. This is the first report of cembrene A from a vertebrate; the
      ketone has not been described previously.

PMID- 9287419
TI  - Trypanocidal flavonoids from Trixis vauthieri.
AB  - The crude extract of Trixis vauthieri (Asteraceae) was active against the
      trypomastigote forms of Trypanosoma cruzi, the protozoan that causes Chagas'
      disease. Bioassay-guided fractionation of this extract afforded the trypanocidal
      flavonoids 5,4'-dihydroxy-7-methoxyflavanone (1) and 5,4'-dihydroxy-3,6,7
      trimethoxyflavone (2) besides the inactive flavonoids 3,5,4'-trihydroxy-7
      methoxyflavanone (3) and 5,4'-dihydroxy-3,6,7,8-tetramethoxy flavone (4). The
      trypanocidal activity of 1 and 2 and the presence of compounds 2 and 4 in Trixis
      vauthieri are reported here for the first time.

PMID- 9287420
TI  - Structure and anti-acetylcholinesterase activity of 4 alpha-(hydroxymethyl)-4
      alpha-demethylterritrem B.
AB  - The structure of a metabolite produced on incubation of territrem B (1) with rat
      liver microsomes has been established to be 4 alpha-(hydroxymethyl)-4 alpha
      demethylterritrem B (5). Compound 5 was a potent inhibitor of electric eel
      acetylcholinesterase (AChE) (E.C. 3.1.1.7).

PMID- 9287421
TI  - A new flavone C-glycoside and antiplatelet and vasorelaxing flavones from
      Gentiana arisanensis.
AB  - A new flavone C-glycoside, isovitexin 6"-O-glucoside (1), and three known
      flavonoids, quercetin, isovitexin, and luteolin-7-O-beta-D-glucoside, have been
      further isolated from the whole plant of Gentiana arisanensis Hayata. The new
      compound was characterized by spectral methods and chemical reactions. The
      antiplatelet effects of isovitexin 6"-O-glucoside (1), isoorientin (2), 2
      peracetate (3), isovitexin (4), luteolin 7-O-beta-D-glucoside (5), luteolin (6),
      isoorientin 6"-O-glucoside (7), and 7 peracetate (8) were studied using washed
      rabbit platelets. Of the compounds tested, 6 showed potent antiplatelet effects
      on arachidonic acid (AA)-induced platelet aggregation (IC50 = 43.5 microM). The
      effect of 2, 5, and 6 on the contraction of rat thoracic aorta was also studied.
      Compound 6 depressed markedly the contraction induced by Ca2+ (1.9 mM) in high-K+
      (80 mM) medium, with an IC50 of about 156 microM and also inhibited noradrenaline
      (3 microM)-induced phasic and tonic contractions, with an IC50 of about 68 and 72
      microM, respectively.

PMID- 9287422
TI  - Widespread and ancient distribution of a noncanonical genetic code in
      diplomonads.
AB  - Recently, a group of diplomonads has been found to use a genetic code in which
      TAA and TAG encode glutamine rather than termination. To survey the distribution
      of this characteristic in diplomonads, we sought to identify TAA and TAG codons
      at positions where glutamine is expected in genes for alpha-tubulin, elongation
      factor-1 alpha, and the gamma subunit of eukaryotic translation initiation factor
      2. These sequences show that the variant genetic code is utilized by almost all
      diplomonads, with the genus Giardia alone using the universal genetic code.
      Comparative phylogenetic analysis reveals that the switch to this genetic code
      took place very early in the evolution of diplomonads and was likely a single
      event. Termination signals and downstream untranslated regions were also cloned
      from three Hexamita genes. In all three of these genes, the predicted TGA
      termination codon was found at the expected position. Interestingly, the
      untranslated regions of these genes are high in AT. This is incongruent with the
      coding regions, which are comparatively GC-rich.

PMID- 9287423
TI  - Molecular phylogeny of the major arthropod groups indicates polyphyly of
      crustaceans and a new hypothesis for the origin of hexapods.
AB  - A phylogeny of the arthropods was inferred from analyses of amino acid sequences
      derived from the nuclear genes encoding elongation factor-1 alpha and the largest
      subunit of RNA polymerase II using maximum-parsimony, neighbor-joining, and
      maximum-likelihood methods. Analyses of elongation factor-1 alpha from 17
      arthropods and 4 outgroup taxa recovered many arthropod clades supported by
      previous morphological studies, including Diplopoda, Myriapoda, Insecta,
      Hexapoda, Branchiopoda (Crustacea), Araneae, Tetrapulmonata, Arachnida,
      Chelicerata, and Malacostraca (Crustacea). However, counter to previous studies,
      elongation factor-1 alpha placed Malacostraca as sister group to the other
      arthropods. Branchiopod crustaceans were found to be more closely related to
      hexapods and myriapods than to malacostracan crustaceans. Sequences for RNA
      polymerase II were obtained from 11 arthropod taxa and were analyzed separately
      and in combination with elongation factor-1 alpha. Results from these analyses
      were concordant with those derived from elongation factor-1 alpha alone and
      provided support for a Hexapoda/Branchiopoda clade, thus arguing against the
      monophyly of the traditionally defined Atelocerata (Hexapoda + Myriapoda).

PMID- 9287424
TI  - Mutation accumulation in nuclear, organelle, and prokaryotic transfer RNA genes.
AB  - A comparative analysis of the transfer RNA genes in the genomes of the major
      kingdoms of eukaryotes and prokaryotes leads to the general conclusion that the
      rate of evolution of organelle tRNA genes is typically equal to of greater than
      that of their nuclear counterparts. Situations where this is not the case, most
      notably in vascular plants, are attributable to an elevated mutation rate in the
      nuclear genome. Through a comparison of rates of mutation with rates of
      nucleotide substitution, it is shown that there is a reduction in the efficiency
      of selection on new mutations in organelle genes. Numerous lines of evidence,
      including observed reductions in stem duplex stability and changes in loop sizes,
      suggest that the excess changes observed in the organelle genes are mildly
      deleterious. Uniparental inheritance of organelles causes a reduction in the
      efficiency of selection through the joint effects of an increase in linkage
      disequilibrium and a decrease in effective population size. These results provide
      molecular support for the idea that asexually propagating genomes are subject to
      long-term, gradual fitness loss and raise questions about the role of organelle
      mutations in the long-term survival of major phylogenetic lineages.

PMID- 9287425
TI  - Biased mutations and microsatellite variation.
AB  - Mutation bias is one of the forces that may constrain the variation at
      microsatellite loci. Here, we study the dynamics of population statistics and the
      genetic distance between two populations under multiple stepwise mutations with
      linear bias and random drift. Expressions are derived for these statistics as
      functions of time, as well as at mutation-drift equilibrium. Applying these
      expressions to published data on humans and chimpanzees, the regression
      coefficient of mutation bias on allele size was estimated to be at least between 
      0.0064 and -0.013. The assumption of mutational bias produces larger estimates of
      divergence times than are obtained in its absence; in particular, the time of
      split between African and non-African human populations is estimated to be
      between 183,000 and 222,000 years, assuming one-step mutations and no selection.
      With multistep mutations, the divergence time is estimated to be lower.

PMID- 9287426
TI  - Evolution of SINE S1 retroposons in Cruciferae plant species.
AB  - The S1 element is a plant short interspersed element (SINE) that was first
      described and studied in Brassica napus. In this work, we investigated the
      distribution and the molecular phylogeny of the S1 element within the Cruciferae
      (= Brassicaceae). S1 elements were found to be widely distributed within the
      Cruciferae, especially in species of the tribe Brassiceae. The molecular
      phylogeny of S1 elements in eight Cruciferae species (Brassica oleracea, Brassica
      rapa, Brassica napus, Brassica nigra, Sinapis, arvensis, Sinapis pubescens,
      Coincya monensis, and Vella spinosa) was inferred using 14-36 elements per
      species. Significant neighbor-joining and maximum-parsimony phylogenetic
      clusters, supported by high bootstrap P values and/or represented in 100% of the
      most-parsimonious trees, were observed for each species. Most of these clusters
      probably correspond to recent species-specific bursts of S1 amplification. Since
      these species diverged recently, S1 amplification in Cruciferae plants is
      proposed to be a highly dynamic process that could contribute to genome
      rearrangements and eventually lead to reproductive isolation. S1 sequence
      analysis also revealed putative gene conversion events that occurred between
      different S1 elements of a given species. These events suggest that gene
      conversion is a minor but significant component of the molecular drive governing
      S1 concerted evolution.

PMID- 9287427
TI  - Molecular evolution of the Amy multigenes in the subgenus Sophophora of
      Drosophila.
AB  - Molecular evolution of the Amy multigenes in Drosophila was investigated using
      PCR amplification. Twenty-five partial Amy sequences from 13 species belonging
      mainly to the subgenus Sophophora were determine, and a molecular phylogeny of
      the Amy genes in Drosophila was constructed, together with published Amy
      sequences. Clustering of species are mostly consistent with the traditional
      classification and that inferred from other genes. From sequence divergence
      between PCR products, several species, including D. elegans and D. fuyamai, were
      suggested to have multiple copies of the Amy genes. The loss of an intron took
      place at least three times after the Sophophora radiation. In order to
      investigate the mechanism of sequence evolution, the numbers of amino acid
      replacement and synonymous substitutions in five lineages were estimated. The
      heterogeneity in the relative numbers of synonymous and replacement substitutions
      among the lineages was found. Possible roles of selection in the sequence
      evolution of the Amy gene are discussed.

PMID- 9287428
TI  - Phylogenetic relationships among prokaryotic and eukaryotic catalases.
AB  - Seventy-four catalase protein sequences, including 29 bacterial, 8 fungal, 7
      animal, and 30 plant sequences, were compiled, and 70 were used for phylogenetic
      reconstruction. The core of the resulting tree revealed unique, separate groups
      of plant and animal catalases, two groups of fungal catalases, and three groups
      of bacterial catalases. The only overlap of kingdoms occurred within one branch
      and involved fungal and bacterial large-subunit enzymes. The other fungal branch
      was closely linked to the group of animal enzymes. Group I bacterial catalases
      were more closely related to the plant enzymes and contained such diverse taxa as
      the Gram-positive Listeria seeligeri, Deinocococcus radiodurans, and gamma
      proteobacteria. Group III bacterial sequences were more closely related to fungal
      and animal sequences and included enzymes from a broad range of bacteria
      including high- and low-GC Gram positives, proteobacteria, and a bacteroides
      species. Group II was composed of large-subunit catalases from diverse sources
      including Gram positives (low-GC Bacilli and high-GC Mycobacteria),
      proteobacteria, and species of the filamentous fungus Aspergillus. These data can
      be interpreted in terms of two gene duplication events that produced a minimum of
      three catalase gene family members that subsequently evolved in response to
      environmental demands. Horizontal gene transfer may have been responsible for the
      group II mixture of bacterial and fungal large-subunit catalases.

PMID- 9287429
TI  - Phylogenetic evidence for role-reversals of gender-associated mitochondrial DNA
      in Mytilus (Bivalvia: Mytilidae).
AB  - Distinct gender-associated mitochondrial DNA (mtDNA) lineages (i.e., lineages
      which are transmitted either through males or through females) have been
      demonstrated in two families of bivalves, the Mytilidae (marine mussels) and the
      Unionidae (freshwater mussels), which have been separated for more than 400 Myr.
      The mode of transmission of these M (for male-transmitted) and F (for female
      transmitted) molecules has been referred to as doubly uniparental inheritance
      (DUI), in contrast to standard maternal inheritance (SMI), which is the norm in
      animals. A previous study suggested that at least three origins of DUI are
      required to explain the phylogenetic pattern of M and F lineages in freshwater
      and marine mussels. Here we present phylogenetic evidence based on partial
      sequences of the cytochrome c oxidase subunit I gene and the 16S RNA gene that
      indicates the DUI is a dynamic phenomenon. Specifically, we demonstrate that F
      lineages in three species of Mytilus mussels, M. edulis, M. trossulus, and M.
      californianus, have spawned separate lineages which are now associated only with
      males. This process is referred to as "masculinization" of F mtDNA. By extension,
      we propose that DUI may be a primitive bivalve character and that periodic
      masculinization events combined with extinction of previously existing M types
      effectively reset the time of divergence between conspecific gender-associated
      mtDNA lineages.

PMID- 9287430
TI  - The geographic apportionment of mitochondrial genetic diversity in east African
      chimpanzees, Pan troglodytes schweinfurthii.
AB  - This study is a geographically systematic genetic survey of the easternmost
      subspecies of chimpanzee, Pan troglodytes schweinfurthii. DNA was noninvasively
      collected in the form of shed hair from chimpanzees of known origin in Uganda,
      Rwanda, Tanzania, and Zaire. Two hundred sixty-two DNA sequences from
      hypervariable region 1 of which of the mitochondrial control region were
      generated. Eastern chimpanzees display levels of mitochondrial genetic variation
      which are low and which are similar to levels observed in humans (Homo sapiens).
      Also like humans, between 80% and 90% of the genetic variability within the
      eastern chimpanzees is apportioned within populations. Spatial autocorrelation
      analysis shows that genetic similarity between eastern chimpanzees decreases
      clinically with distance, in a pattern remarkably similar to one seen for humans
      separated by equivalent geographic distances. Eastern chimpanzee mismatch
      distributions (frequency distributions of pairwise genetic differences between
      individuals) are similar in shape to those for humans, implying similar
      population histories of recent demographic expansion. The overall pattern of
      genetic variability in eastern chimpanzees is consistent with the hypothesis that
      the subject has responded demographically to paleoclimatically driven changes in
      the distribution of eastern African forests during the recent Pleistocene.

PMID- 9287432
TI  - Conservative management of ureteric stones.
AB  - The authors review the current conservative management of ureteric stones. The
      physiopathology of the renal colic is analyzed with its implications in the
      medical treatment. The role of NSAID is enhanced. Stone size and stone location
      are to be considered when evaluating the possibility of spontaneous passage of
      the stone. Stones less than 3 mm in diameter of the lower ureter will pass
      spontaneously in 90% of the cases while stones more then 6 mm in the upper ureter
      will not pass in most cases. The role of stone dissolution in uric acid and
      cystine stones is discussed. SWL is not controversial in the management of upper
      stones less than 15 mm in size. The authors report their experience with SWL of
      ureteric stones in upper, middle or lower ureteric stones with a success rate of
      respectively 87%, 65% and 84%.

PMID- 9287431
TI  - New data on diagnosis and medical treatment of retroperitoneal fibrosis.
AB  - A review of the literature of the last 5 years on retroperitoneal fibrosis is
      given. MRT seems to add to the exact extend of the disease and
      galliumscintigraphy can give new information on the activity of the process and
      the usefulness of medical therapy. The use of corticosteroid or other
      immunosuppressive drugs such a azathioprine, again is confirmed. Other drugs
      mentioned in the medical therapy are methotrexate, cyclophosfamide and
      penicillamine. A few cases responded well to tamoxifen, a drug which was already
      used in therapy of desmoid tumours. Medical treatment is anyhow superior to
      surgery alone.

PMID- 9287433
TI  - Endoscopical management of ureteral trauma.
AB  - Ureteric injuries are encountered with increasing frequency. Adequate definitions
      and etiologies are discussed. All treatment modalities are summarised with
      special attention for the use of JJ stents, the different endourological
      approaches and "urological pearls".

PMID- 9287434
TI  - Treatment of the neonatal and infant megaureter in reflux, obstruction and
      complex congenital anomalies.
AB  - Controversy exists about the timing of surgery in neonates and infants with
      congenital anomalies such as refluxing and/or obstructing megaureters and ectopic
      ureteroceles. Discussion acuminates to the fact whether or not early
      reconstruction causes irreversible damage to the urodynamic properties of the
      bladder. Between 1986 and 1992, 49 neonates and infants with obstructing or
      refluxing megaureters and 23 neonates and infants with ectopic ureteroceles have
      been operated in our hospital with a mean follow-up of 7.3 years. Reimplant
      surgery consisted of a modified Politano Leadbetter procedure, ureterocele
      surgery consisted of complete excision of the ureterocele, including the urethral
      part, with reconstruction of the urethra, bladder neck and bladder base combined
      with ureteral reimplants. Urodynamically no unexpected changes or deteriorisation
      have been seen in any of the patients. Bladder capacity for age, especially in
      the reflux group, averages 200%. Two of the ureterocele patients needed clean
      intermittent catheterisation for several years. Results of reflux cure in
      megaureter surgery were disappointing in ureters with a flat diameter between 6
      and 9 mm's that were not recalibrated leading to the conclusion that in young
      children recalibration of the distal ureter should be done from 6 mm's upwards.
      No post-operative ureteral obstruction was observed in any of the cases. The
      conclusion is that early major reconstructions of the lower urinary tract causes
      no specific harm to the urodynamic properties of the bladder and pelvic floor,
      provided that the surgery is performed by specialised pediatric urological
      surgeons. The reported urodynamic problems in this patient group are probably
      related to lack of experience to deal with dysfunctional voiding habits that are
      quite common in these children, also after successful surgery. These micturation
      problems are not related to the surgical procedures, they are the result of pre
      existing urodynamic changes of bladder function in these children.

PMID- 9287435
TI  - Megaureter in childhood: conservative or surgical management?
AB  - Antenatal and incidentally diagnosed megaureters can be safely treated
      conservatively after careful work up by combined imaging technics. Serial and
      repeated imaging are non the less usually necessary to confirm the diagnosis.
      This aspect could be fastidious and expensive. In case of symptoms, breakthrough
      infections or loss of kidney function, surgical treatment should be considered
      and good results can be expected. Refluxing megaureter has to be considered as
      high grade reflux and surgical approach is more often suggested. The authors have
      reviewed the experience of 139 patients with megaureters treated in the last
      decade to illustrate those facts.

PMID- 9287437
TI  - The forces of healing: reflections on energy, consciousness, and the beef
      stroganoff principle.

PMID- 9287436
TI  - Can NPTR data predict the cause of organic impotence?
AB  - Conventional diagnostic evaluation, including color duplex doppler ultrasound of
      the penile vessels, pharmaco-cavernosometry, intracavernosal drug testing and
      neurologic tests, were used to classify 78 patients with complaints of erectile
      impotence into one of the following three groups: non-organogenic, arteriogenic,
      vascular and neurogenic impotence. Nocturnal penile tumescence and rigidity
      (NPTR) measurements were also performed. Differentiation between patients with
      organic and non-organic impotence proved possible. The "best night" and "best
      erection" alone could not outline a pathognomonic pattern for the different
      causes of organic impotence.

PMID- 9287438
TI  - 'Guilt' and 'responsibility' must be differentiated.

PMID- 9287439
TI  - Taking issue with animal studies.

PMID- 9287440
TI  - The abiding importance of cultural context for 'twins'.

PMID- 9287441
TI  - Article misses the mark on 'supernatural' healing.

PMID- 9287442
TI  - Alternative medicine on the Internet.

PMID- 9287443
TI  - Riverside Methodist Hospitals: partnering with patients on pain control.

PMID- 9287444
TI  - Revisiting accepted wisdom in the management of breast cancer.
AB  - Misconceptions and illusions prevail in the management of breast cancer.
      Historical review reminds us that medical practice is commonly rooted in
      tradition rather than proof. The Halsted mastectomy inadvertently served the
      burgeoning profession of surgery in the early 20th century more than it has
      benefited women with breast cancer, yet 100 years later the operation continues
      to thrive. Despite evidence that mastectomy, radiation following lumpectomy,
      axillary node dissection, or intensive follow-up surveillance have little impact
      on survival, these practices are adhered to tenaciously. The extent to which
      current treatment for breast cancer succeeds in prolonging life remains open to
      question. Many accepted ideas and interventions are perilously disconnected from
      their true merit. The imperative for doctors to do something sometimes
      contradicts their pledge to do no harm. Reflection on what is known should guide
      future action.

PMID- 9287445
TI  - An exploration of the meaning and use of spirituality among women with HIV/AIDS.
AB  - Disease progression and the onset of AIDS slowly strip away the human form and
      dignity. As the physical body succumbs to the disease, those with HIV/AIDS search
      for meaning in life as they seek ways to prolong survival. The purpose of this
      study was to explore the meaning and use of spirituality in women infected with
      HIV/AIDS. Data were generated through the use of focus group methodology in eight
      sessions. The sample was composed of 45 women, aged 20 to 63, of whom 12 were
      white and 33 were black. Focus group sessions generated 76 descriptions of
      spirituality and six major themes: relationship with a supreme being, prayer and
      meditation, healing, peace, love, and religiosity. The acceptance of spirituality
      as a component of health and quality of life requires a shift in perspective that
      may allow for the development of new treatment and care strategies that are
      meaningful to those whose conditions are presently incurable.

PMID- 9287446
TI  - Coping, life attitudes, and immune responses to imagery and group support after
      breast cancer treatment.
AB  - BACKGROUND: The pilot study used clinical trial methodology to differentiate the
      effects of imagery and support on coping, life attitudes, immune function,
      quality of life, and emotional well-being after breast cancer. METHODS: Women (N
      = 47) who completed treatment for primary breast cancer, excluding stage IV, were
      randomly assigned to standard care (n = 15) or six weekly support (n = 16) or
      imagery (n = 16) sessions. Self-report measures included Ways of Coping-Cancer,
      Life Attitude Profile, Quality of Life (FACT-B), Profile of Mood States, and
      Functional Support. Immune measures included natural killer cell activity, plasma
      neopterin, interferon-gamma, interleukins 1 alpha, 1 beta, and 2, and beta
      endorphin levels. Differences between groups over time were tested using general
      linear models, adjusted for pretest score and covariates (age, stage, and months
      posttreatment). RESULTS: For all women, interferon-gamma increased, neopterin
      decreased, quality of life improved, and natural killer activity remained
      unchanged. Compared with standard care, both interventions improved coping skills
      (seeking support) and perceived social support, and tended to enhance meaning in
      life. Support boosted overall coping and death acceptance. When comparing imagery
      with support, imagery participants tended to have less stress, increased vigor,
      and improved functional and social quality of life. CONCLUSION: Although imagery
      reduced stress and improved quality of life, both imagery and support improved
      coping, attitudes, and perception of support. The clinical implications of these
      changes warrant further testing.

PMID- 9287447
TI  - Participant assessment of a nonmedical breast cancer support group.
AB  - BACKGROUND: This study was designed to examine how a particular format of a
      support group for women with breast cancer was related to the use of the group
      and experiences of the participants. SUBJECTS: A total of 131 women who
      participated in a breast cancer support group under the auspices of the YWCA were
      interviewed. RESULTS: Findings replicated existing studies indicating such
      generic benefits of support group participation as enhanced sense of control,
      sharing of information and experiences, and acquaintance with positive role
      models. In addition to these benefits, participants reacted favorably to the
      opportunities provided by a drop-in format, an exercise component, and
      opportunities for sharing in a nonmedical setting. Active use of the group was
      associated with lack of emotional support from family. Active use also was
      associated with favorable reported outcomes for well-being and health.

PMID- 9287449
TI  - Complementary medicine in the Nordic countries.

PMID- 9287448
TI  - Susan Love, MD. What we really know about breast cancer and HRT. Interview by
      Bonnie Horrigan.

PMID- 9287450
TI  - Government is not the problem.

PMID- 9287451
TI  - Let's join the consumer revolution.

PMID- 9287452
TI  - Delivery of vaccines to adults: correlations with physician knowledge and patient
      variables.
AB  - Our objective was to explore reasons why vaccines are not provided to adult
      patients receiving primary health care. The study setting was a primary health
      care clinic in a urban hospital staffed primarily by residents and teaching
      faculty. The patients were identified as all continuity care patients with a
      scheduled visit to the clinic during the 4-week study period in April 1995. The
      providers were all primary care providers for the patients during the study
      period. The providers were given two surveys before the study: one to assess
      their knowledge of published preventive health care guidelines and one to assess
      their perspective of the guidelines. During the study period, the charts of the
      patients were reviewed for the services they had received. An assessment was
      placed in each patient's chart for the provider's completion during the visit.
      The assessment enabled the provider to explain why services had not been
      provided. The results showed that influenza, pneumococcal, and diphtheria-tetanus
      vaccines were provided at varying rates. Each vaccine had a different profile as
      to noncompliance with guidelines. Lack of provider knowledge of the guideline was
      most apparent with pneumococcal vaccine. Providers' ambivalence regarding the
      scientific basis and/or clinical importance was most apparent with influenza
      vaccine. Patient refusal was a prominent cause with influenza vaccine in the
      elderly. Patient appointment behavior (opportunity for care and compliance) also
      seemed to play an important role. We conclude that explanations for nondelivery
      of vaccines to adults seem to be multiple. Lack of physician knowledge and
      physician perception of the guidelines provide some explanations. Patient-related
      factors including refusal, decreased opportunity for care, and noncompliance also
      play important roles in why vaccinations are not provided. Improvement in the
      rates at which immunizations to adults are provided will require interventions in
      multiple areas.

PMID- 9287453
TI  - Assessing medical care of dying residents in nursing homes.
AB  - Although approximately one of five people in the United States die in nursing
      homes (NHs), little has been written about their quality of dying, including the
      quality of terminal medical care. The purpose of this study is to review actual
      medical practices in NHs to suggest factors important for delivering good quality
      terminal care. Four NHs were surveyed for management of residents who died in
      1992. A convenience sample of charts of newly admitted and longer term residents
      were abstracted for demographic variables, death, diagnostic categories, and
      various laboratory and other parameters. Charts of those residents who died were
      further reviewed using indicators of quality medical care, such as presence of
      advance directives, control of pain, and control of dyspnea, based upon recent
      published clinical practice guidelines for terminal care in NHs. Three hundred
      and seventy-one charts were abstracted. Forty-one charts documented the
      resident's death. We found that NHs without regulatory difficulties usually had
      expected deaths that were managed approximately as measured by terminal medical
      care quality indicators. NHs with a history of regulatory difficulties had a
      higher prevalence of residents who died suddenly and unexpectedly, often with
      problems in the quality of care as measured by the same indicators. There was a
      correspondence between physician certification, antemortem diagnosis of terminal
      illness, and appropriate terminal care. We conclude that physicians are able to
      recognize impending death and redirect the medical care of dying NH residents
      toward goals of terminal care management. This is more likely to occur in a NH
      environment that places greater emphasis upon total quality management. We
      suggest that another indicator in providing good NH terminal care is the
      physician's performance in predicting a short life expectancy.

PMID- 9287454
TI  - Commentary: extended care paths and the continuum of care.

PMID- 9287455
TI  - Validity of clinical information from a maternity survey.
AB  - This research was designed to validate data collected through a survey--an
      inexpensive way to provide information for quality measurement. The survey was
      sent to health maintenance organization (HMO) enrollees who had given birth(s)
      between October 1, 1994, and May 31, 1995. The responses were compared with the
      medical records. A sample of 407 women was randomly selected from the completed
      surveys. Medical records were reviewed for 89.9% (362/407) of the sample based on
      medical record availability. Over 98% of responses agreed with the medical record
      information regarding whether there were cesarean sections for previous
      deliveries (kappa = 1.0), cesarean section for recent delivery (kappa = 0.95),
      and vaginal birth after cesarean section (kappa = 0.96). Over 99% of the mothers
      agreed with the information regarding whether the newborn birth weight was under
      2500 g (kappa = 0.91). The findings strongly support the validation of this
      instrument. Using this validated instrument enables health plans to cost
      effectively obtain crucial information.

PMID- 9287456
TI  - Using proprietary methods to evaluate acute care admissions to a Veterans Affairs
      tertiary care center: are the appropriateness criteria appropriate?
AB  - An important question for facilities monitoring acute care bed admissions with
      proprietary criteria is whether these methodologies remain valid after
      substantial changes to the criteria sets. This is especially true for publicly
      funded hospitals whose medical and social mission is often broader than that of
      private sector facilities for which insurance-based claim review is most
      relevant. To further address this issue, we used sequential sets (1994 and 1995)
      of InterQual Intensity, Severity, and Discharge criteria to assess a cohort of
      patients referred to our Veterans Affairs facility as acute care admissions
      between December 1, 1994, and February 28, 1995. We found that the
      appropriateness rate for the subset of medical admissions dropped from 88% when
      using the 1994 criteria set to 49% when using the more stringent 1995 criteria
      set (P < 0.001). We conclude that substantive changes to previously validated
      criteria sets require revalidation. Furthermore, consideration should be given to
      the role that insurance-based utilization review should play in publicly funded
      hospital systems.

PMID- 9287457
TI  - The introduction of ambulatory electrocardiographic monitoring for the diagnosis
      and management of myocardial ischemia.
AB  - We report on the introduction of a new technology and a new method for the
      management of chronic coronary artery disease into a managed care environment.
      The introduction incurred substantial resistance from subspecialty consultants,
      primary care physicians, and top management. Strategies were developed to
      overcome these resistances. Modification of the program as well as the
      development of incentives occurred. These measures continue to evolve. The
      program, to date, has achieved approximately 50% penetration. The demonstration
      of better health outcomes and financial savings will almost certainly temper the
      resistance encountered from all three groups identified.

PMID- 9287458
TI  - Meningococcal disease in Australia; looking at the past, thinking of the future.
AB  - In 1987 an unexpected change in the epidemiology of meningococcal disease began
      in Australia. The change was accompanied by an outbreak of serogroup A
      meningococcal disease among Aboriginal central Australians, and was followed by a
      progressive rise in notifications of disease caused by both serogroup B and C
      nationwide. Over the last 4 years, the notification rate has plateaued at 2.1-2.3
      per 100,000 population. Virulent clonal groups of serogroup A and C meningococci
      that have caused outbreaks appear to be identical to strains that have caused
      large outbreaks in other countries. We cannot predict where and when the next
      outbreak will occur. However, we can plan to respond swiftly when it does. This
      report presents an overview of the observed trends, the association between the
      microbiology and epidemiology of meningococcal disease, and the relevance of this
      association to outbreaks, with recommendations for management.

PMID- 9287459
TI  - Communicable diseases surveillance.

PMID- 9287460
TI  - High frequency of leukemic lymphomas with osteosarcomas but no myeloid leukemias
      in C3H mice after 239Pu citrate injection.
AB  - Female C3H strain mice, which do not spontaneously exhibit frequent bone tumors
      and myeloid leukemias, were injected intraperitoneally with various doses of 10
      to 12,000 Bq/animal of monomeric 239Pu citrate to clarify lifetime carcinogenesis
      caused by alpha-particles distributed mainly in the skeleton. Survival time was
      reduced significantly at mean skeletal doses of more than 2.93 Gy and was
      accompanied by marked life-shortening as compared to the controls due to an
      earlier increase in neoplastic or non-neoplastic death. Bone tumors, almost all
      of which were osteosarcomas, were not found in the controls, whereas their
      incidence increased sharply to a maximum of 96% at 6.92 Gy, then dropped at
      higher doses (20% at 42.4 Gy). Although lymphoid tumors were present in 20% of
      the control animals, their incidence dropped to zero at 6.92 Gy, then increased
      at higher doses (36% at 25.5 Gy). Non-thymic, mostly pre-B cell type, leukemic
      lymphomas mainly occurred at early time after 239Pu-injection; whereas, in the
      controls thymic, lymphocytic or histiocytic lymphomas occurred only at a later
      time. Of the other soft tissue tumors, neither myeloid leukemias nor myelogenous
      neoplasms were found in the controls or the 239Pu-injected animals. Tumors
      affecting the lungs, liver, ovaries, and skin were much fewer or not found at
      mean doses of more than 2.93 Gy. These results indicate dose-dependent,
      differential tumor induction resulting from bone and lymphoid tumor competition
      after an injection of plutonium.

PMID- 9287461
TI  - Effects of continuous low-dose prenatal irradiation on neuronal migration in
      mouse cerebral cortex.
AB  - We investigated the effects of continuous exposure to gamma-rays during
      corticogenesis on the migration of neuronal cells in developing cerebral cortex.
      Pregnant mice were injected with 0.5 mg of bromodeoxyuridine (BrdU) on day 14 of
      gestation to label cells in the S phase. The mice were then exposed to 137Cs
      gamma-rays (dose rates of 0.1, 0.3, and 0.94 Gy/day) continuously for 3 days.
      Brains from 17-day-old embryos and from offspring at 3 and 8 weeks after birth
      were processed immunohistochemically to track the movements of BrdU-labeled
      cells. Comparative analyses of the distribution pattern of BrdU-labeled cells in
      the cerebral cortex revealed that (1) the migration of neurons was delayed during
      the embryonic period in mice irradiated at 0.94 Gy/day, (2) in 3-week-old mice,
      there was a significant difference in the distribution pattern of BrdU-labeled
      cells in the cerebral cortex between the mice irradiated prenatally and control,
      and (3) in 8-week-old mice, there were no differences in the distribution pattern
      of BrdU-labeled cells between control and animals irradiated with 0.1 and 0.3
      Gy/day. In contrast, in the animals irradiated with 0.94 Gy/day, the significant
      difference in the distribution pattern of the labeled cells relative to control
      was maintained. These results suggest that the migration of neuronal cells in
      mouse cerebral cortex is disturbed by continuous prenatal irradiation at low-dose
      and some modificational process occurred during the postnatal period.

PMID- 9287463
TI  - Analysis of relative biological effectiveness of high energy heavy ions in
      comparison to experimental data.
AB  - We report that the relative biological effectiveness (RBE) of accelerated heavy
      ions for inactivation of cells can be analyzed by using the quadratic dependence
      on the linear energy transfer (LET) of the cellular effect. For high-LET
      radiation in low-dose regions, the inactivation cross section (sigma) can be
      approximately expressed as sigma max [1-exp[-k.(LET/Li)2]; here, k is the number
      of heavy-ions traversed in a cell nucleus and Li is a geometrical parameter
      related to the DNA structure, which depends on cell type. This original
      expression was first presented by Powers et al [Int. J. Radiat. Biol. 14 (1968)].
      Using this expression and the Poisson distribution for the stochastic property of
      particle hitting, the mortality of cell populations was calculated. The numerical
      results were compared to the RBE values recently obtained with Chinese hamster
      V79 cells, and an Lt value of 152 keV/micron was found to give the best fit. At
      LETs of between 30 and 500 keV/micron, the D10 values (10% survival dose) agreed
      with the experimental data within an error range of -15%-(+8%).

PMID- 9287462
TI  - Concentration-dependent modes of cell death in Chinese hamster V79 cells after
      treatments with H2O2.
AB  - Deterioration in the clonogenic ability of Chinese hamster V79 cells was observed
      after treatments with low concentrations of H2O2 (0.06-0.2 mM) for 1 h and
      subsequent incubation for 6-8 days, whereas no loss of ability of the cells to
      exclude trypan blue after treatments with H2O2 for 1 h and subsequent incubation
      for 6 h was observed in this concentration range. The loss of the dye-exclusion
      ability became observable when the cells were treated with concentrations greater
      than 0.9 mM H2O2 for 1 h and subsequently incubated for 6 h. Agarose gel
      electrophoresis of DNA extracted from cells treated with 1-5 mM H2O2 showed
      specific regular fragmentation of DNA, suggesting that apoptotic cell death was
      induced. The induction of apoptotic cell death was further confirmed by observing
      the protective effects of several modifiers, a protein synthesis inhibitor
      (cycloheximide), a Ca(2+)-chelator (BAPTA-AM) and an antioxidative compound PBN),
      against cell survival and DNA fragmentation. From these results, it was concluded
      that apoptotic cell death was induced by H2O2 in Chinese hamster cells at high
      concentrations, where their clonogenic ability completely disappeared.

PMID- 9287465
TI  - Comparison of oxidation products from DNA components by gamma-irradiation and
      Fenton-type reactions.
AB  - The four 2'-deoxyribonucleosides were gamma-irradiated or were aerobically
      treated with Fenton-type-reagents, Fe(II)-EDTA or a renal carcinogen Fe(II)
      nitrilotriacetic acid (NTA) under the neutral conditions. The reaction mixtures
      were immediately analyzed by reverse-phase HPLC. Major products detected were 2
      hydroxydeoxyadenosine (2-OH-dA), 8,5'-cyclodeoxyadenosine (cyclo-dA), 8
      hydroxydeoxyadenosine (8-OH-dA). 5-formyldeoxyuridine (5-CHO-dU), 5
      hydroxydeoxycytidine (5-OH-dC), 8-hydroxydeoxyguanosine (8-OH-dG), 8,5'
      cyclodeoxyguanosine (cyclo-dG), and glyoxal and its adduct with dG. Ratio of
      these oxidized products were dramatically changed depending upon the agents used.
      For example, 2-OH-dA was a modified nucleoside produced most efficiently by
      Fe(II)-EDTA, while 5-CHO-dU and 5-OH-dC were the major products by the Fe(II)-NTA
      treatment and gamma-irradiation, respectively. Glyoxal itself was estimated to be
      produced most frequently (13 folds of 8-OH-dG) when treated with Fe(II)-EDTA, but
      its formation was not detected by the treatment with Fe(II)-NTA or by gamma
      irradiation. 8-OH-dA was not produced by Fe-EDTA or Fe-NTA but was produced by
      gamma-irradiation. In contrast, 2-OH-dA was not produced by gamma-irradiation.
      These results suggest that triphosphates of 2-OH-dA, cyclo-dA, 8-OH-dA, cyclo-dG,
      5-CHO-dU, 5-OH-dC, and glyoxal-dG as well as 8-OH-dG may be produced in cells
      with different ratio by various types of oxidative stress and involved in
      mutagenesis and carcinogenesis.

PMID- 9287464
TI  - Acceleration of granulocytic cell recovery in irradiated mice by a single
      subcutaneous injection of a heat-killed Lactobacillus casei preparation.
AB  - Flow cytometric analysis showed that the treatment of irradiated mice with a heat
      killed Lactobacillus casei preparation (LC 9018) accelerated the recovery of
      granulocytic cell populations in peripheral blood, spleen and femur bone marrow.
      The recovery of the lymphocytic cell population was not accelerated while the
      recovery of the B-lymphocytic cell population was inhibited. Histological
      analysis also showed that the LC-9018 treatment markedly enhanced granulopoiesis
      in the spleen and bone marrow of irradiated mice. The same LC-9018 treatment
      significantly increased 30-day survival rates of athymic nude mice after lethal
      whole-body irradiation. The recovery of the granulocytic cell population in
      peripheral blood of irradiated athymic nude mice was also accelerated by LC-9018
      treatment. Our results suggest that LC 9018 protected lethally irradiated mice
      from bone marrow death by enhancing granulopoiesis rather than lymphopoiesis and
      that the contribution of activated T lymphocytes to the enhancement of the
      granulopoiesis was small.

PMID- 9287466
TI  - Treatment of spontaneous pneumothorax in a rural hospital setting.

PMID- 9287468
TI  - The relationship between physicians' malpractice claims history and later claims:
      does the past predict the future?

PMID- 9287467
TI  - Case records of the Department of Medicine University of Mississippi Medical
      Center. Leukocytoclastic vasculitis, probable polyarteritis nodosa, clinically
      indolent lymphoma, but never firmly established.

PMID- 9287470
TI  - Interview with Jean Kerwin. Interview by Robin K. Levinson.

PMID- 9287469
TI  - Socially-assisted dying and people with disabilities: some emerging legal,
      medical, and policy implications.

PMID- 9287472
TI  - Pets helping to heal the elderly.

PMID- 9287471
TI  - The golden boom: the health needs of seniors.

PMID- 9287473
TI  - Video-assisted esophageal myotomy for achalasia.

PMID- 9287475
TI  - Home care: old concepts and new technologies.

PMID- 9287474
TI  - Oh, my aching head: treating headaches.

PMID- 9287476
TI  - Taking care of their own: how professionals deal with impairment.

PMID- 9287477
TI  - MSNJ's Legal Consultant Network.

PMID- 9287478
TI  - The role of radiologic methods in assessing body composition and related
      metabolic parameters.
AB  - The measurement of body composition and related metabolic parameters has become
      an important issue in clinical nutrition. Numerous techniques to assess visceral
      fat, which is strongly associated with metabolic disorders, have been developed.
      Other techniques focus mainly on the measurement of specific body components
      related to metabolic disturbances. This paper reviews methods that directly
      assess body composition and associated metabolic parameters. The principles of
      these methods and their accuracy, reproducibility and safety, as well as the
      clinical implications of their use, are discussed. Recent studies have documented
      the safety and efficacy of radiologic methods of assessing visceral fat, muscle
      mass, and morphology to obtain body composition data related to metabolic
      disturbances. Because these techniques have been documented to be safe and
      effective, clinicians should consider using them in the evaluation and follow-up
      of patients with various conditions.

PMID- 9287479
TI  - Three cases of comprehensive dietary therapy and pharmacotherapy of patients with
      complex obesity-related diseases.
AB  - The effect of weight loss with anorectic medications on sleep apnea, non-insulin
      dependent diabetes, and steatohepatitis is illustrated in three cases from
      practice in a clinical nutrition setting. Prevention of obesity, a chronic
      disorder, is preferable, but when obesity becomes a major obstacle in the care of
      patients with respiratory, cardiovascular, and metabolic disorders and
      osteoarthritis, an intense course of weight reduction using anorectic medications
      under medical and dietetic guidance is essential for patients' survival and
      reduction of medical cost.

PMID- 9287480
TI  - Dietary pattern and hypertension: the DASH study. Dietary Approaches to Stop
      Hypertension.

PMID- 9287481
TI  - Importance of adequate vitamin A status during iron supplementation.
AB  - Nutritional deficiencies, including iron deficiency, may promote infection by
      lowering the body's resistance to infectious diseases. However, it has been shown
      that administration of iron in developing countries can result in increased
      morbidity, because pathogenic bacteria may compete effectively for iron in the
      circulation, resulting in an exacerbation of existing infections. Improved
      vitamin A status may protect against this potentially harmful effect of iron
      supplementation in environments where infections are highly prevalent.

PMID- 9287482
TI  - Retinoic acid as a therapy for emphysema?
AB  - In concert with its action as a morphogen during embryonal development, retinoic
      acid appears to be able to regenerate lung alveoli in an experimental model of
      elastase-induced emphysema in rats, thereby inhibiting manifestation of the
      disease. The application to humans is now an interesting possibility.

PMID- 9287483
TI  - A half-century perspective on world nutrition and the international nutrition
      agencies.
AB  - This paper reviews the birth and evolution of the international nutrition agenda.
      International nutrition issues of today are discussed, as are recommendations and
      projections for the future.

PMID- 9287484
TI  - Center for Food Safety and Applied Nutrition.

PMID- 9287485
TI  - Retinoids: from hindbrain patterning to Parkinson disease.

PMID- 9287486
TI  - Mammalian artificial chromosomes and chromosome transgenics.

PMID- 9287487
TI  - Transgenic plants: environmentally safe factories of the future.

PMID- 9287488
TI  - The spreading influence of heterochromatin.

PMID- 9287489
TI  - A Human Genome Evolution Project is needed.

PMID- 9287490
TI  - The Eph receptor family: axonal guidance by contact repulsion.
AB  - Eph receptors and their ligands have been implicated in axonal pathfinding during
      the formation of neuronal networks. Whereas other guiding molecules, such as
      netrins and most semaphorins, are diffusible factors that can guide axons over
      considerable distances, Eph receptors and their ligands are cell-surface bound
      and are, therefore, involved in short-range contact-mediated guidance. Those
      molecules that have been analyzed appear to guide axons by repelling the growth
      cone, rather than attracting it. Here, we summarize the known biological
      functions of Eph receptors and ligands focusing on the developing nervous system,
      and we review the data on possible mechanisms of action.

PMID- 9287491
TI  - Evolutionary origins and maintenance of redundant gene expression during metazoan
      development.
AB  - Various levels of redundancy in developmental gene function appear common in
      complex metazoans. There might be no apparent phenotype at many, or even any, of
      a gene's specific expression sites in homozygous null mutant embryos. Here we ask
      what underlies the origin of such arrangements. The generation of families of
      genes by duplication has clearly been important. Additionally, however, selection
      might have driven molecularly unrelated genes, which encode proteins of similar
      physiological function, to become expressed during the same sets of developmental
      events (times and places), even though each such gene might initially have
      evolved in connection with just one of these events.

PMID- 9287492
TI  - Modular regulation of muscle gene transcription: a mechanism for muscle cell
      diversity.
AB  - Skeletal, cardiac and smooth muscle cells express overlapping sets of muscle
      specific genes, such that some muscle genes are expressed in only a single muscle
      cell lineages. Recent studies in transgenic mice have revealed that, in many
      cases, multiple, independent cis-regulatory regions, or modules, are required to
      direct the complete developmental pattern of expression of individual muscle
      specific genes, even within a single muscle cell type. The temporospatial
      specificity of these myogenic regulatory modules is established by unique
      combinations of transcription factors and has revealed unanticipated diversity in
      the regulatory programs that control muscle gene expression. This type of
      composite regulation of muscle gene expression appears to reflect a general
      strategy for the control of cell-specific gene expression.

PMID- 9287494
TI  - A database for post-genome analysis.

PMID- 9287493
TI  - Gene trapping and functional genomics.
AB  - Classical genetics depends upon investigation of function by random destruction
      with little information on structure. Modern mapping using random polymorphisms,
      cloning and sequencing investigates structure without function. The genome
      projects with their rapid gene discovery are, however, redefining classical
      genetic approaches. The efficient translation of this wealth of new information
      into insights in biological function at molecular, cellular and organismal levels
      requires large-scale approaches to the generation of mutants. Gene trapping in
      embryonic stem (ES) cells allows an efficient approach to the functional analysis
      of the murine genome. The usually separate processes of gene discovery, mapping,
      the observation of the expression pattern and the mutant phenotype in vivo, can
      be integrated by the use of an indexed library of insertionally mutated ES cell
      clones. It should be possible to generate mutants for a large proportion of the
      genes of the mammalian genome.

PMID- 9287495
TI  - It's a knockout!

PMID- 9287496
TI  - Expanded programme on immunization (EPI). Progress towards poliomyelitis
      eradication, WHO Eastern Mediterranean Region.

PMID- 9287498
TI  - Zoonoses control. Rabies situation and trends in Asia.

PMID- 9287499
TI  - Declaration of Olympia on Nutrition and Fitness. Ancient Olympia, Greece, May 28
      29, 1996.

PMID- 9287500
TI  - Diet, physical activity, and health: policies for the new millennium.

PMID- 9287501
TI  - Evolutionary aspects of diet: old genes, new fuels. Nutritional changes since
      agriculture.

PMID- 9287502
TI  - Paleonutrition and modern nutrition.

PMID- 9287504
TI  - Genetic variation: nutrients, physical activity and gene expression.

PMID- 9287503
TI  - Evolutionary aspects of exercise.

PMID- 9287506
TI  - Nutritional needs of the exercising child.

PMID- 9287505
TI  - Genetics, response to exercise, and risk factors: the HERITAGE Family Study.

PMID- 9287507
TI  - Health-related physical activity and fitness among European children and
      adolescents.

PMID- 9287508
TI  - Nutrition and physical activity perspectives for all Americans: government and
      private sector partnerships for the twenty-first century.

PMID- 9287509
TI  - National policies promoting better nutrition, physical fitness and sports for all
      in China.

PMID- 9287510
TI  - National programs and policies promoting better nutrition, physical fitness and
      sports for all: experiences from Africa.

PMID- 9287511
TI  - National programs and policies promoting better nutrition, fitness and sports for
      all in Greece.

PMID- 9287512
TI  - National policies for promoting physical activity, physical fitness and better
      nutrition in Europe.

PMID- 9287513
TI  - National policies promoting better nutrition, physical fitness and sports for all
      in Australia.

PMID- 9287514
TI  - Is physical activity promotion on the primary health care agenda?

PMID- 9287516
TI  - Health promotion: enlarging our scope of vision.

PMID- 9287515
TI  - "Co-opetition": a model for multidisciplinary practice.

PMID- 9287517
TI  - Health promotion in the Hutterite community and the ethnocentricity of
      empowerment.
AB  - Empowerment, one of the cornerstones of health promotion, has been influenced by
      the transformative and emancipatory perspectives of the revolutionary educator
      Paulo Freire and critical social theory. The empowerment process is conceived as
      one of liberation from oppression, powerlessness, and ignorance, and at its core
      are notions of grassroots activism and rejection of the status quo. This paper
      critically examines the challenges faced by health-promotion practitioners and
      researchers who seek to work in an empowering way with a culturally distinct
      group, the Hutterites. The Hutterian world-view, which values (a) communalism,
      (b) respect for hierarchical decision-making, and (c) strict adherence to a
      traditional code of conduct, values, and beliefs, provides an opportunity to
      critique the ethnocentricity of the empowerment process.

PMID- 9287518
TI  - The Adolescent Lifestyle Questionnaire: development and psychometric testing.
AB  - This paper describes the development and psychometric testing of an instrument
      designed to measure healthy lifestyle in adolescents. The Adolescent Lifestyle
      Questionnaire (ALQ) was tested on 292 adolescents residing in eastern Canada
      using item analysis, factor analysis, and reliability measures. Factor analysis
      isolated seven dimensions to a healthy lifestyle in adolescents, which accounted
      for 56.0% of the variance in the 43-item measure. The seven factors were:
      identity awareness, nutrition, physical participation, safety, health awareness,
      social support, and stress management. The alpha reliability coefficient for the
      total scale is .91; alpha coefficients for the subscales range from .60 to .88.
      The instrument warrants further testing and development with different adolescent
      populations. The instrument will enable researchers to investigate lifestyle
      patterns in adolescents and to assess the impact of interventions of lifestyle
      change in this population.

PMID- 9287519
TI  - The "social determinants" of practice? A critical analysis of the discourse of
      health promotion.
AB  - Developments in the practice of health promotion have centred on considerations
      of what clients bring to their encounters with professionals. This changes in the
      provider-client relationship marks a significant departure from practice models
      that relied on the professional giving the client expert health instructions. The
      literature that seeks to illuminate these more contemporary relationships with
      clients tends to ignore what practitioners bring to the health promotion
      encounter and, significantly, the social conditions that underlie the encounter.
      This paper, drawing on research gathered during an ethnographic study of practice
      in a public health clinic, critically analyzes health promotion with a view to
      challenging researchers, educators, and practitioners concerning the health
      promoting possibilities in existing practice settings.

PMID- 9287520
TI  - Health promotion: issues for the year 2000.

PMID- 9287521
TI  - Development and testing of the Primary Health Care Questionnaire (PHCQ): results
      with students and faculty in diploma and degree nursing programs.
AB  - Primary health care (PHC) has been proposed as a key strategy for improving the
      health of the world community, and nurses are acknowledged as key health-care
      professionals in meeting this goal. Efforts to have nurses implement PHC policies
      presuppose that they are knowledgeable about this approach to health care and
      have positive attitudes. The underlying aim of this study was to develop a
      measure of knowledge, attitudes, and practices in PHC and to assess the
      reliability and validity of the measure with a sample of student nurses and
      faculty in degree and diploma programs. The Primary Health Care Questionnaire
      (PHCQ) is a three-part self-report measure that provides quantitative data on
      knowledge and attitudes and qualitative data on practices of PHC. The instrument
      was developed from a rigorous review of the literature and systematic feedback
      from two panels (local and national) expert in PHC. Data were collected from 457
      students and faculty in one four-year degree program (three sites), one post
      diploma degree program, and three diploma programs, in a western Canadian
      province. Internal consistency reliability estimates using Cronbach's alpha were
      .76 (knowledge) and .85 (attitudes). Test-retest reliability at two weeks was r =
      .67 (knowledge) and .76 (attitudes). Content validity was enhanced through a
      systematic review of the instrument by a two-phase local and a national expert
      panel. Findings indicated greater knowledge and more positive attitudes among
      senior compared to junior students, degree compared to diploma students, and
      faculty compared to students. These findings lend support to the validity of the
      measure. The qualitative data revealed that learning opportunities related to PHC
      were built into both the diploma and the degree program through classroom
      teaching, clinical practice, and written assignments.

PMID- 9287522
TI  - Clarifying the nature of conceptualizations about nursing.
AB  - This discipline of nursing is at a crucial point in its development.
      Conceptualizations about nursing are being developed and tested without benefit
      of a clear conception as to their nature. Consequently, the nursing literature on
      the topic tends to confuse rather than clarify thought. The purpose of this
      philosophic treatise is to show that greater clarity could be achieved by
      acknowledging the fact that questions addressed in conceptions about nursing are
      philosophic in nature. The influential thought of Jacqueline Fawcett is critiqued
      with reference to how acknowledging and acting in terms of this fact would also
      lend parsimony to thought on the matter.

PMID- 9287523
TI  - The ethical theory of existential authenticity: the lived experience of the art
      of caring in nursing administration.
AB  - The purpose of this research was to conduct a study of the art of caring in
      nursing administration. By means of a phenomenologic-hermeneutic approach, the
      caring experiences of six nurse administrators were revealed and analyzed.
      Essential themes emerged from their descriptions of their experiences.
      Interpretation of the data served as the lens through which the expressions of
      the art of caring related to archetypical philosophies of art: living form,
      imitation, and expression. An ethical theory, Existential Authenticity, was
      uncovered as the unity of meaning of nursing administrative caring art. This
      unity of meaning embodied statespersonship, which was viewed by Plato as the
      highest form of art. Implications for the transformation of nursing
      administrative practice as an ethical caring enterprise by the manifestation of
      statespersonship are presented.

PMID- 9287524
TI  - Centres for health promotion research in Canada.

PMID- 9287525
TI  - An issue that affects us all.

PMID- 9287526
TI  - Men in nursing.

PMID- 9287528
TI  - HIV collaboration project.

PMID- 9287527
TI  - Discharge planning isn't working.

PMID- 9287530
TI  - Sexual health care: the role of the nurse.

PMID- 9287531
TI  - Minimizing transfer injuries.

PMID- 9287529
TI  - The physician-nurse relationship in family practice.

PMID- 9287532
TI  - Nurses, computers and confidentiality.

PMID- 9287533
TI  - Surely you jest: bringing humour to the workplace.

PMID- 9287534
TI  - What do nurses do?

PMID- 9287535
TI  - Keeping up with health care technologies.

PMID- 9287537
TI  - Why do a Whipples?

PMID- 9287536
TI  - Patient-centered care in the OR: is this possible?
AB  - Patient-centered care can be practiced in high technology areas such as the
      operating room if care-givers develop an attitude of seeing their care delivery
      through the patient's eyes. Through caring interactions with our patients, we can
      find out what matters most to them. It seems that the more complex our technology
      and the more bureaucratic our hospitals have become, the less respect and
      positive regard is being communicated to patients. In addition, time is becoming
      increasingly scarce in our busy operating rooms. However, it is not how much time
      we spend with our patients. Instead, it is how we are with our patients in these
      stressful moments before surgery. Using concepts of relational care discussed in
      current nursing literature, nurses can evolve from a technically dominant care
      giving paradigm towards a humanistic paradigm that focuses on the patient's
      expressed needs. This enables our clients to experience health and healing in
      their context.

PMID- 9287538
TI  - From theory to perioperative practice with Parse.
AB  - The operating room nurse today is often thought of as a task skilled, highly
      technical, process oriented, and efficient member of the operating room team. Too
      often her/his nursing education and preparation in practice, theory and
      discipline are overlooked. Perioperative nursing as a specialty is an important,
      vital factor in the success of the planned surgical intervention. Perioperative
      nursing practice involves caring for the patient; it is patient-centered rather
      than task oriented. The RN combines both the physiologic and psychosocial aspects
      of nursing in delivery of care. This is reflective of the theoretical model used
      to plan effective nursing care. The RN interacting with the preoperative patient
      has a focus on being in true presence with the patient (Parse, 1987). The
      interrelationship sets in motion utilization of theory, reflecting nursing
      knowledge and practice.

PMID- 9287539
TI  - Innocence lost in first harvesting.

PMID- 9287541
TI  - Laughter in leadership: bringing out your lighter side.

PMID- 9287540
TI  - Making meaning and care.

PMID- 9287542
TI  - A bridge to unite nursing. Interview by Marie Manthey.

PMID- 9287543
TI  - Preparing students for leadership in practice.

PMID- 9287545
TI  - Confronting diversity: experiences of nurses in a sanatorium.
AB  - Tuberculosis has been identified as a major health problem in South Africa.
      Although the trend is towards treatment from clinics, in certain cases patients
      are admitted to a sanatorium, which means that they may come into contact with
      nursing staff whose frame of reference regarding tuberculosis frequently differs
      from their own. In this contact situation a number of problems were seen to
      arise, both as a result of circumstances within the sanatorium and because many
      patients retain health-beliefs of a more traditional kind. The purpose of this
      study is to investigate how some nurses who are confronted with socio-cultural
      diversity in a sanatorium experience and deal with such problems. A number of
      strategies that may be applied in approaching socio-cultural diversity are
      suggested from an anthropological perspective Data were collected during
      interviews with members of the nursing staff of a sanatorium.

PMID- 9287546
TI  - Programme evaluation in problem-based and community-based nursing education.
AB  - The article outlines a case study of formative evaluation of a new Master's
      Degree Programme in Nursing Education. The programme based on a model of problem
      and community learning is offered at a major South African university. While the
      findings of the external evaluators are presented, the meta- (second order)
      evaluation is discussed, providing some current limitations in the evaluation of
      problem and community-based degree programmes. Guidelines to overcome these
      limitations are suggested.

PMID- 9287547
TI  - Attitudes of nursing students towards the seminar method of teaching.
AB  - After experiencing problems associated with student-centred teaching methods, the
      researcher resolved to undertake a study on the attitudes of the student nurses
      towards the seminar method of teaching. A survey was undertaken among twenty five
      third and fourth year student nurses. The instrument for collecting data was a
      questionnaire. From the study it is clear that: negative attitudes exist towards
      the seminar method of teaching in spite of students' awareness of its
      contribution to self-directed learning. The majority of student nurses of the
      basic nursing programme are adolescents who resent any time consuming academic
      commitment which interferes with their private life. Lack of correlation between
      teaching methods used at high school and those used at the nursing college leads
      to poor adjustment to seminar method as a student-centred, independent learning
      method. Library facilities are inadequate which makes it more difficult and more
      time consuming for student nurses to find suitable material for preparation of
      quality presentations.

PMID- 9287548
TI  - The importance of traditional midwives in the delivery of health care in the
      Republic of South Africa.
AB  - From the data collected during qualitative research, in 1995, to determine the
      possibility of collaboration with traditional healers a number of themes were
      highlighted. The different types of traditional healers, the way in which they
      operate as well as the importance of collaboration was identified. In this
      article the contributions of traditional midwives in rendering health care,
      especially in the rural areas in the Northern Cape and the Free State will be
      discussed. The data was collected during interviews and observations, done over a
      period of seven months. When the respondents could not speak English or Afrikaans
      an interpreter was used. Interviews were also conducted with health care staff
      and patients. The contributions of the traditional midwives are of utmost
      importance and should not be discouraged. With the necessary training the
      traditional midwives could help in providing an effective and efficient health
      service to pregnant women. Traditional midwives have been an integral part of
      African medicine for centuries. This is not only because African people still
      love and fear the spirits, but also because a great number of the South African
      population do not have access to existing health services. This is especially so
      in the rural areas and informal settlements. According to the Reconstruction and
      Development Programme (RDP) of the Government of National Unity it is important
      that everyone who could make a contribution towards the provision of health care
      should be involved. This view is supported in the ANC Health Plan and a Policy
      Document for the Development of a District Health System for South Africa, where
      it is stated that traditional healers (traditional midwives are included in this
      category) could play a role in the delivery of health care. The research on which
      the article is based was done to determine the role traditional healers could
      play in collaboration with primary health care services. In this article only the
      role of the traditional midwife will be discussed.

PMID- 9287549
TI  - Community surveys: the benefits and sacrifices.
AB  - Community-based research is becoming more important, especially with the
      introduction of the RDP and the changing role of NGOs. Community surveys are a
      part of this new research approach. This paper enters the debate around the role
      and importance of surveys. A case study of a community survey done in Mfuleni by
      the Western Cape Community Partnership Project will be used to illustrate the
      points made. Key considerations are raised in terms of the potential for the
      community survey to be useful. These include the role of the survey in providing
      information and assisting in the process of the development of the project as a
      whole. In addition the cost effectiveness plus the ethical and political
      dimensions are considered. In the course of the survey important lessons were
      learned that could benefit others also doing research of this type. Issues raised
      include the importance of the presence of specific research skills being part of
      the team throughout the project, the importance of full negotiation of access,
      being clear in terms of objectives and the questions to be asked, sampling
      issues, problems of questions demanding memory recall, community participation
      and spreading of skills, and the dissemination of results.

PMID- 9287551
TI  - A comparison between nursing degree programmes offered at the University of Malta
      and the University of Fort Hare.
AB  - The purpose of thus study was to compare the undergraduate nursing programme of
      the Institute of Health Care of the University of Malta with that of the
      Department of Nursing Sciences of the University of Fort Hare. Historical facts
      about each institution are briefly described followed by a more detailed
      description of the respective undergraduate programmes. The programmes are
      compared according to the curriculum content and assessment strategy used for
      each. Although both programmes are four year degree programmes, distinct
      similarities, and differences in the curricular content and assessment strategies
      are noted and discussed.

PMID- 9287550
TI  - The effect of violence on primary health care nurses in selected areas of the
      former Natal region.
AB  - An exploratory descriptive study aimed at analyzing problems confronting nurses
      in primary health care settings during civil unrest is described. Data were
      collected by means of open and closed ended questionnaires. The response is
      recorded from twenty five participants who completed the questionnaire. Data
      analysis showed that nurses who were directly or indirectly affected by violence
      at work or at home were unable to render health care effectively. Experiences of
      harassment, intimidation and physical abuse were reported. Recommendations
      include what employers and professional organisations could do for the nurses
      trapped in socio-political violence.

PMID- 9287553
TI  - Preparing educators for problem-based and community-based curricula: a student's
      experiences.
AB  - The Department of Nursing at the University of Natal Durban (UND) introduced a
      one year Masters Degree in Progressive Education for Health Professionals in
      1996, the aim of which is to prepare educators of health professionals to
      understand better innovative methods of teaching, learning and more specifically
      problem-based learning (PBL) and community-based education (CBE). The author of
      this paper is a registered nurse and this paper focuses on her experiences as a
      student in this programme. Most of the experiences gained are related to the use
      of a Personal and Academic Development Portfolio, which covered activities from
      both her own classes and those related to facilitation of basic student's
      learning.

PMID- 9287552
TI  - The reliability of hand-written and computerised records of birth data collected
      at Baragwanath hospital in Soweto.
AB  - This study examined the reliability of hand written and computerised records of
      birth data collected during the Birth to Ten study at Baragwanath Hospital in
      Soweto. The reliability of record-keeping in hand-written obstetric and neonatal
      files was assessed by comparing duplicate records of six different variables
      abstracted from six different sections in these files. The reliability of
      computerised record keeping was assessed by comparing the original hand-written
      record of each variable with records contained in the hospital's computerised
      database. These data sets displayed similar levels of reliability which suggests
      that similar errors occurred when data were transcribed from one section of the
      files to the next, and from these files to the computerised database. In both
      sets of records reliability was highest for the categorical variable infant sex,
      and for those continuous variables (such as maternal age and gravidity) recorded
      with unambiguous units. Reliability was lower for continuous variables that could
      be recorded with different levels of precision (such as birth weight), those that
      were occasionally measured more than once, and those that could be measured using
      more than one measurement technique (such as gestational age). Reducing the
      number of times records are transcribed, categorising continuous variables, and
      standardising the techniques used for measuring and recording variables would
      improve the reliability of both hand-written and computerised data sets.

PMID- 9287554
TI  - Barriers to cervical screening: women's and health workers' perceptions.
AB  - Cancer of the cervix is the most common cause of cancer mortality among Black
      South African women. Mortality can be reduced by an effective screening
      programme. Such a programme is being considered for implementation in South
      Africa. It is important that the implementation of a national screening programme
      be based on solid understanding of the current situation as well as the
      anticipated barriers to the effectiveness of the programme. This qualitative
      study was done at three rural sites in order to explore the barriers to effective
      utilisation of cervical screening from the perspectives of women and health
      workers. The aim was to inform the local service organisers as well as the policy
      process when planning the new screening programme. There were interesting
      similarities and differences between the barriers that were identified by the
      health workers and those by the women. Those identified by the health workers
      included several structural problems associated with the service such as busy
      clinics and problems of access including lack of transport, the mobility of the
      people and opposition from men. None of the women spoke of these service and
      access factors. Women emphasised issues surrounding the actual procedures which
      were based on their experiences and information they had gained from friends and
      other community networks. The barriers identified by women are amenable to change
      through careful attention to health education and the circumstances of the test.
      If the new screening policy is to be implemented nationally and be successful in
      recruiting cervical cancer cases, nurses will have a key role in identifying and
      overcoming barriers to smear uptake at a local level. This study has shown the
      importance of listening to patients in this process.

PMID- 9287555
TI  - Communication with TB patients; a neglected dimension of effective treatment?
AB  - Previous research has shown that patients who are satisfied with their
      interactions with a health provider tend to adhere to treatment. This study sets
      out to investigate the quality of the communication in the interactions between
      clinic nurses at a Western Cape clinic and newly notified tuberculosis patients.
      Routine interviews between clinic nurses and tuberculosis patients were video
      recorded, transcribed and analysed, using a qualitative instrument devised by the
      researchers. The interactions were evaluated as being essentially nurse-centred;
      there was an unequal distribution of control, poor receptivity to the patient and
      little confirmation of the patient. The nursing staff received a period of
      training in communication skills. After this training their interviews with
      patients revealed a significant shift towards a more patient-centred approach,
      resulting in mutual satisfaction of nurse and patient. Training in communication
      skills should be introduced at TB clinics, in order to improve patients'
      adherence to therapy.

PMID- 9287556
TI  - Factors associated with the increased number of caesarean sections at Nkhensani
      Hospital.

PMID- 9287559
TI  - Yet another late-breaking story: Adam take back your rib.

PMID- 9287560
TI  - Cultural priorities and elder care: the impact on women.
AB  - In this article I address the institutional and personal processes associated
      with providing and receiving elder care. Although cultural differences abound, it
      is argued that five conditions currently affect the social response to frail
      elders all around the world: (a) male dominance of political and economic social
      institutions; (b) elder care dependent on the "dirty work" of women; (c) limited
      and ambiguous social recognition for providing elder care; (d) the aging of
      population as a whole (i.e., the proportion of old people in the world is
      increasing; and (e) frail old women fare worse than do frail old men. Regardless
      of which institution (government, economic marketplace, or family) has assumed
      the responsibility for elder care, the decision-making role has been dominated by
      men, and household tasks have been disproportionately provided by women. Women's
      elder-care work is physically draining. It tends to be work for which the
      providers receive, even within cultural boundaries, what is considered to be
      inadequate compensation. Nevertheless, women continue to provide labors of duty
      and labors of love. What is truly remarkable is that so many women report that
      their efforts are emotionally and spiritually satisfying. However, increasingly
      researchers report that women also experience depression and burnout. I discuss
      the extent to which the five current conditions of elder care will impede the
      performance of elder care in the future.

PMID- 9287561
TI  - AIDS-related risk behaviors and safer sex practices of women in midlife and older
      in the United States: 1990 to 1992.
AB  - Women in midlife and older represent over 25% of all women with AIDS and 4% of
      all reported AIDS cases in the United States. We present prevalence estimates and
      demographic correlates of AIDS-related risk behavior and safer sex practices
      among women in midlife and older from the National AIDS Behavioral Surveys
      (NABS). Data are of women aged 40 to 75 in the (a) NABS 1 national sample (n =
      887), (b) NABS 1 urban sample (n = 2,111), and (c) NABS 2 national sample (n =
      624). Data from the baseline survey (NABS 1) revealed that approximately 8% or
      4.5 million women aged 40 to 75 engaged in behaviors that might expose them to
      HIV. Data from the follow-up survey (NABS 2) indicated that the proportion of
      women who reported a risk factor remained at about 8%. Overall safer sex
      practices among older women who reported sexual risk behaviors were minimal.
      Between 90% and 100% had not used condoms in the previous 6 months. Moreover,
      almost 90% of the women who reported a risk behavior did not perceive themselves
      to be at risk.

PMID- 9287562
TI  - Auxiliary nurses in Mexico: impact of multiple roles on their health.
AB  - As more women worldwide enter the labor force, debate has been generated over how
      this additional work role influences women's health. In this study, we explored
      the work, maternal, and spousal roles of 59 auxiliary nurses in two university
      affiliated Mexican hospitals. Participants completed questionnaires that included
      demographics, a women's roles interview protocol, a self-rating of health status,
      and the Cornell Medical Index (CMI). No significant correlation was found between
      the perception of their health status and the number of roles, amount of role
      involvement, or their perceived levels of stress and satisfaction in any of their
      three roles. Work stress was significantly correlated with the number of physical
      symptoms (r = .30, p < .05), longer periods of standing (r = .31, p < .05), more
      muscle strain (r = .53, p < .01), eye problems (r = .43, p < .01), frequent
      changes in environmental temperature (r = .30, p < .05), and perceptions of
      economic inadequacy (r = .37, p < .01). Years of education was not related to any
      health measure or degree of stress or satisfaction in any of the roles. The
      greater the degree of role integration, that is, the greater the sum of
      satisfactions minus stresses of each role, the fewer the physical symptoms (r =
      .48, p < .05) and the fewer total symptoms (r = .43, p < .05) reported on the
      CMI. Those with more spousal stress reported more work-related muscle strain (r =
      .35, p < .05), and working mothers with three or more children tended to perceive
      themselves as less healthy (r = .75, p < .01). Thus, analyzing the
      interrelationship of women's multiple roles is a better predictor of health than
      examining specific role stresses in isolation.

PMID- 9287563
TI  - Trends in fertility patterns of women in rural Zimbabwe.
AB  - To study changes over time in reproductive health and living conditions of women
      in a rural setting in Zimbabwe, 12 villages were selected at random in the Gutu
      district, Masvingo province. During two study periods in 1992 and 1993, 1,213
      women of fertile age (15-44 years) were interviewed and examined. Median age at
      menarche was 15 years, with a decrease of 0.4 years from the oldest to the
      youngest age group. There has been no increase in the mean height of women,
      indicating no change in determinants of nutritional status of girls in childhood
      and adolescence. Younger women still marry at a median age of 19 years but prefer
      smaller families. Level of education is the main determinant for age at marriage
      and preferred family size. A low prevalence of primary (1%) as well as secondary
      infertility (4%) was found in spite of the currently reported high prevalence of
      sexually transmitted diseases in Zimbabwe.

PMID- 9287564
TI  - Medical education, women's status, and medical issues' effect on women's health
      in the Caribbean.
AB  - At an international conference in 1992 on women and health, an attempt was made
      to redefine health concerns for women of the English-speaking Caribbean in the
      1990s. Medical practices in developing countries change as advances are made in
      public health; clinical issues on the islands now resemble those in the United
      States (e.g. hypertension, cancer, sexually transmitted diseases, domestic
      violence, and abortion). In the Caribbean, however, these problems exist in a
      unique socioeconomic context, and women's health there suffers indirectly because
      of cultural mores. Gender bias in medical education and practice influences
      treatment of women and obstructs their advancement to policy-making levels in the
      design and delivery of programs that bear on maternal and child health, among
      others. The effect of local cultural beliefs and practices on women's health must
      be considered when setting goals and direction for health policy if aid or
      educational programs are to be effective.

PMID- 9287565
TI  - The impact of women on women's health research: an interview with Dr. Ruth
      Wilson. Interview by Lisa Calder.
AB  - As women become more prominent players in the health sciences, it seems logical
      to ask the question, How are women affecting issues of health specific to women?
      Few authors have addressed this important query. In this article, I look at the
      views of a female researcher with respect to the literature about women's health
      research and the impact of women researchers on the information exchange between
      patient and physician, provider competence, and continuity of care. These factors
      all affect the quality of care being received by women in many different areas of
      health care.

PMID- 9287566
TI  - Toward a women-centered health care system: women's experiences, women's voices,
      women's needs.
AB  - In this report we describe the results from 19 focus groups of nearly 250 women
      held in 1993 and 1994, in which diverse groups of women were asked to respond to
      a model health care delivery system. This project, sponsored by the Women's
      Health Advisory Committee of the San Francisco Department of Public Health,
      solicited focused input from diverse groups of women as they reviewed the draft
      of an "ideal" women's health care service model. Women's responses to an ideal
      system revealed some of the problems inherent with the current "nonsystem" of
      health care delivery. These responses were categorized into general themes and
      are presented here to demonstrate the range of women's experiences with their
      current health care, from their perspective and in their voices.

PMID- 9287567
TI  - The nursing profession in the media. A public image to cheerish.

PMID- 9287568
TI  - [A nurse who has put her mark on psychiatry: France Frechette].

PMID- 9287570
TI  - [A poster session brings forth the students' projects on clinical intervention].

PMID- 9287569
TI  - [The poster, an intelligent choice for scientific communication].
AB  - The dissemination of knowledge is a fundamental duty in any discipline, and
      nurses are increasingly required to communicate the results of their clinical or
      theoretical accomplishments. In recent years, thanks to computerization and other
      technological advances, poster sessions have become a preferred instrument for
      communicating scientific information to a large audience. After presenting the
      advantages of this type of communication, the authors-two nurses and a programmer
      analyst-deal with the essentials of creating a poster, from choosing a type of
      poster, its content and its visual design to planning the necessary human and
      material resources. They then describe the delivery of a poster session and
      stress the importance of evaluating the experience. Their technical advice on
      such matters as the choice of materials, colours and illustrations will be a
      valuable resource for those who are considering a poster session as a vehicle for
      scientific communication.

PMID- 9287571
TI  - [Physical examination. What does it do for us?].

PMID- 9287572
TI  - Of change, challenges, communication and collaboration...

PMID- 9287573
TI  - Patient-controlled analgesia compared with nurse-controlled infusion analgesia
      after heart surgery.
AB  - A randomized, controlled clinical trial was conducted on 66 patients undergoing
      elective cardiac surgery to compare patient-controlled analgesia (PCA) to nurse
      controlled analgesia (NCA) with continuous morphine infusion. Hourly assessment
      of pain (at rest and on movement) using a visual analogue scale (VAS), of
      respiratory rate, and level of sedation took place for the 24 h following
      extubation. The incidence of nausea was also recorded. Mean pain scores were
      calculated, and peak pain and sedation scores, together with lowest respiratory
      rates, were identified. Morphine consumption was measured at 24 h. No significant
      differences were found between the groups' scores for pain or sedation. The PCA
      group had significantly lower respiratory rates (P = 0.02) and a lower incidence
      of nausea (P = 0.008). The PCA group also consumed significantly more morphine (P
      = 0.0001). The study suggests a beneficial effect from PCA after cardiac surgery
      in reducing nausea, compared to NCA. It confirms nurse-controlled infusion
      analgesia as an effective form of pain relief in an intensive care and high
      dependency setting.

PMID- 9287574
TI  - Development of a sedation scoring protocol.
AB  - The creation of a research and development post within the Intensive Therapy Unit
      (ITU) environment at St Helier has provided the opportunity to review all aspects
      of practice to ensure that the care delivered is evidence-based and not merely
      rooted in routines and rituals. The first aspect of care to be examined was our
      sedation practice. It was felt that sedation procedures varied at times and that
      a research-based protocol was necessary to ensure that patients receive optimal
      levels of sedation consistently. A 'sedation scoring group' was set up in order
      to achieve this. Questionnaires were sent to all members of staff and the
      resulting data used to formulate a sedation scoring system and algorithm as well
      as a protocol which included information on sedative drugs and the effects of
      over- and under-sedating patients.

PMID- 9287575
TI  - Dignity in situations of ethical difficulty in intensive care.
AB  - In intensive care, situations of ethical difficulty are common. For the purpose
      of illuminating the meaning of being in ethically difficult situations, 20
      registered nurses (RNs) employed in six intensive care units in Sweden narrated
      episodes of ethical difficulty. From a phenomenological hermeneutic perspective,
      the core theme of 'dignity' was identified in 85 stories. Stories with the
      concept of dignity reveal a threefold meaning; transforming disrespect into
      respect for the inviolable value of the human being; transforming ugly situations
      into beautiful ones; transforming discord of death into togetherness. Stories
      without the concept of dignity were oriented toward skills and physical care
      without reflection on actions and a 'taken-for-granted attitude' that good will
      prevail. Comparing and contrasting stories with and without dignity revealed the
      demands of dignity: attentiveness, awareness, personal responsibility,
      engagement, fraternity and active defence of dignity. In light of the
      philosophies of Weil, Marcel and Ricoeur, the demands of dignity correspond to
      qualities generated when struggling for respecting the dignity of human beings.
      This study reveals that dignity begets dignity, which opens the RNs to the
      ethical dimension. This, in turn, counteracts the risk of dehumanizing care in
      technocratic environments.

PMID- 9287577
TI  - Nursing perspectives for intensive care.
AB  - Within health care, market forces increasingly determine what services have
      economic value. For nursing to survive this economic onslaught, nurses must
      clarify their values and roles. While nurses working in intensive care develop
      useful technical skills and normally work within a constructive multi
      disciplinary team framework, they have a potentially unique contribution to care,
      focusing on the patient as a whole person rather than intervening to solve a
      problem. The need for both physiological and psychological care creates a need
      for holistic values, best achieved through humanistic perspectives. Humanistic
      nursing places patients as people at the centre of nursing care, as illustrated
      by the limitations of reality orientation compared with the potentials of
      validation therapy. Intensive care nurses asserting and developing such patient
      centred roles offer a valuable way forward for nursing to develop into the 21st
      century.

PMID- 9287576
TI  - Old habits die hard: changing paediatric nurses' perceptions of families in ICU.
AB  - Although partnership-in-care is now widely accepted in most areas of paediatrics,
      the intensive care environment is still reluctant to welcome this advancement. In
      an attempt to update visiting guidelines in the Intensive Care Unit (ICU) of a
      major paediatric hospital, a survey of the staff (n = 84) was conducted in July
      1995. The discussion in this paper on the results of the survey will disappoint
      many paediatric nurses. Despite the literature identifying the major stressors
      for families in ICU environments and promoting parental participation, this study
      found that the majority of nursing and medical staff remained unwilling to
      'allow' parents to stay with their child during most procedures. In addition,
      senior nursing staff strongly disapproved of the idea of parents being present
      during resuscitation of their child-'old habits die hard'. The conclusion from
      this pilot study is that although the nurses viewed themselves a 'family
      friendly', in reality they still regard families as 'visitors' who should leave
      when the 'going gets tough'. If paediatric nurses are to meet the needs of
      families adequately, they need to give more than lip-service to the partnership
      in-care philosophy. Acknowledgement of family needs is not enough; implementation
      is required.

PMID- 9287579
TI  - Focus of nursing in critical and acute care settings: prevention or cure?
AB  - The fluidity of the boundaries of critical and acute care can lead to challenges
      for nurses working on acute general wards when caring for post-critical care
      patients and for those in whom a critical care situation arises during a period
      of acute care. The development and use of critical care skills pose special
      difficulties for acute care nurses, because of the acuteness and infrequency of
      such incidents and the diversity of skills the nurses need to possess.
      Nonetheless, critical care is an important component of an acute ward nurse's
      repertoire, particularly in relation to preventing episodes of critical illness.
      It might be expected that the increased provision of high dependency units and
      the formation of postoperative care teams would relieve some of this pressure,
      but such developments are, in fact, more likely to create an increase in overall
      patient acuity. They may, in addition, lead to an over-reliance on the use of
      such facilities and must be implemented carefully in order to bridge, rather than
      widen, the gap between acute and critical care. Critical care is used in this
      paper as a global term, to encompass all settings where patients are usually more
      highly dependent and critically ill than patients on general wards. It includes
      intensive therapy, high-dependency, coronary care and other specialist critical
      care units.

PMID- 9287578
TI  - Ethical considerations relating to terminal weaning in intensive care.
AB  - The ethical considerations relating to terminal weaning from mechanical
      ventilation will be discussed within this paper. The principles of beneficence,
      non-maleficence and autonomy are seen to be the key considerations within the
      discussion. The difference between terminal weaning and regular weaning from a
      ventilator is that it proceeds as vital signs deteriorate and the expected
      outcome is death of the patient. A deterioration in vital signs would normally
      result in a change in the weaning process. The indications for terminal weaning
      have been classified into three categories by Campbell and Carlson. These are the
      patient's informed request to have the ventilator withdrawn, reduction of patient
      pain and suffering and medical futility. These categories will be used to
      facilitate the discussion which will draw on both the relevant literature and
      clinical experience.

PMID- 9287580
TI  - Ethical decision-making in intensive care: are nurses suitable patient advocates?
AB  - According to the United Kingdom Central Council for Nursing, Midwifery and Health
      Visiting (UKCC) code of conduct (1992), nurses in Britain are expected to act as
      patient advocates. An advocate is someone who 'pleads for another' (Concise
      Oxford Dictionary 1982). However, it has been shown that advocacy is a complex
      issue and it is debatable as to whether or not it is a legitimate attribute of
      the role of the nurse (Gates 1995). Mallik (1997) also finds that advocacy can be
      a risky career option. Professional codes of conduct spell out duties, but do not
      give moral guidance. Phrases such as 'promote and safeguard the well-being of the
      patient' (UKCC 1992) are used, but although undoubtedly well-intentioned, this is
      platitudinous and these codes commonly shed little light on how to define an
      action that is to the patient's benefit or detriment. It is tempting to suggest
      that they are used as a drunken man uses a street lamp; more for support than
      illumination. Castledine (1981) identified a number of factors that would make a
      nurse an inappropriate advocate and these will be discussed within the context of
      intensive care units (ICUs).

PMID- 9287581
TI  - Protection of sensitive patient-connected medical devices from the subversive use
      of mobile telecommunication equipment.
AB  - The UK Department of Health has recently advised caution with respect to the
      uncontrolled use of private mobile telecommunication equipment in designated
      sensitive hospital areas. This advice, which has clear implications for patient
      safety and well being, was issued following reports of the interference of
      automatic drug delivery devices, infusion pumps and other sensitive systems. The
      difficulty of monitoring relatives, visitors and, occasionally, staff who use
      such mobile telephones in the sensitive areas has led to an initiative by The
      Princess Margaret Hospital to automatically and continuously monitor the
      frequencies used by the mobile telephones and to initiate an alarm should such
      phones be used within a designated area. This paper describes a protocol for the
      use of these monitors developed in the Princess Margaret Hospital which is
      designed to minimize the number of monitoring units while providing optimum
      departmental cover.

PMID- 9287582
TI  - Amphotericin intravenous preparations.
AB  - Alternative forms of amphotericin injection have been introduced in recent years.
      Though better tolerated and less toxic to kidney tissues, they are substantially
      more expensive than conventional amphotericin and their use is best reserved for
      specific indications.

PMID- 9287583
TI  - Thinking about thinking.
AB  - BACKGROUND: The nursing leadership at a 900-bed tertiary-care facility in the
      southeast believed an opportunity existed to improve the critical thinking
      abilities of the professional nursing staff. METHOD: A team, consisting of a
      diversified group of nurse educators and managers, had the opportunity to gain
      understanding of the critical thinking process of the nursing staff as well as to
      develop a plan designed to improve critical thinking skills. RESULTS: Outputs of
      the team included development of a critical thinking model and process as well as
      an action plan that specifically outlined how it would implement the model within
      the organization using a preceptor-based educational process. CONCLUSION: Nursing
      leadership within this facility believes that nurturing critical thinking in the
      staff will have a positive impact on care delivery outcomes. Creating shared
      visions through the assumptions that the staff and organization hold is important
      to improving care provided. Assisting staff with using a critical thinking
      process in order to construct, tear down, and then reconstruct clinical incidents
      as encouraged by this model is one key to problem-solving.

PMID- 9287584
TI  - A holistic model for moving toward excellence in chaotic times.
AB  - BACKGROUND: Staff development experts in a tertiary-care hospital were searching
      for a holistic approach to facilitating improved outcomes. METHOD: Staff
      development experts, clinical nurse specialists, and clinical managers developed
      a model that provides a framework for educators to integrate their energies with
      those of other leaders in order to create a holistic approach to the goal of
      achieving excellence. RESULTS: The model that is proposed links strategies for
      change with outcome evaluation. CONCLUSIONS: The model provides a conceptual lens
      that helps nurse leaders focus on organizational assessment, strategies to
      improve the work environment, and the evaluation of outcomes. The model is useful
      for guiding practice as well as research.

PMID- 9287585
TI  - Computer-assisted instruction for home study: a new venture for continuing
      education programs in nursing.
AB  - BACKGROUND: Advanced practice nurses (APNs) tested a 5-contact hour home-study
      computer assisted instructional (CAI) program in pharmacokinetics developed by
      the author. METHOD: Twenty-seven APNs enrolled in a traditional lecture
      continuing education course in pharmacology participated in the study. The APNs
      were given a knowledge test and self-efficacy questionnaire before using the CAI
      program and again at the completion of program use. RESULTS: Significant gains in
      knowledge and self-efficacy with large effect sizes were achieved by the program
      users. They cited the convenience, organization and simplicity of use, graphic
      animations, and interactive question sequences as advantages of the program.
      CONCLUSION: Home study by computer may be a feasible option to printed home-study
      and lecture-based continuing education programs in nursing.

PMID- 9287586
TI  - The provision of staff development programs in adult day care centers.
AB  - BACKGROUND: Little is known about staff development activities in adult day care
      (ADC) programs. Therefore, this descriptive study was used to compare existing
      center programs with research- and practice-derived "model staff development
      program" for orientation, inservice education, and continuing education
      opportunities. METHOD: A multi-step mail survey design was used to study licensed
      adult day care programs in Virginia (n = 38). The design produced a 92% (n = 35)
      response rate among eligible respondents. RESULTS: Thirty-seven percent (n = 13)
      of the responding administrators described staff development activities that met
      the criteria for a model program. Despite limited financial support, Virginia
      centers are making an effort to provide comprehensive staff development
      opportunities for their staff. CONCLUSION: Centralized or regionalized
      programming may be two viable solutions for addressing unmet staff training
      issues for these community-based agencies. Moreover, because their staff tend to
      be interdisciplinary in nature, educational programming for an interdisciplinary
      audience will be in order.

PMID- 9287588
TI  - The cultural and critical thinking connection.

PMID- 9287589
TI  - Critical thinking, health policy, and the Hmong culture group, Part I.
AB  - The author discusses the historical connection between the Hmong and the U.S.
      military operations in South Eastern Asia; gives an overview of Hmong culture
      health traditions, such as efficacious, neutral and harmful; socioeconomic data;
      immigration and the local community; and health problems specific to the Hmong.

PMID- 9287587
TI  - Collaborative research among clinical nurse specialists and staff nurses.
AB  - BACKGROUND: Conducting research in clinical settings can be problematic for many
      nurses in practice due to lack of experience and support. METHOD: Research
      collaboration between clinical nurse specialists and staff nurses in clinical
      settings can promote development of their research process skills. RESULTS:
      Strategies identified can be applied by clinical nurse specialists involved in
      continuing education and staff development in clinical practice through further
      research development. CONCLUSION: Collaboration among clinical nurse specialists
      and staff nurses provides a unique and strong link that transcends degrees and
      roles to make substantial contributions to professional nursing practice.

PMID- 9287590
TI  - Life in migrant camps for children-a hazard to health.
AB  - Migrant workers are a national resource as they plant, maintain, harvest, and
      process America's food. However, migrant workers and their children encounter
      many health hazards in the course of providing this service to the nation. This
      article describes life among migrants, and the health hazards to which they are
      constantly exposed.

PMID- 9287591
TI  - Stress and social support among Hispanic student nurses: implications for
      academic achievement.
AB  - This article describes two studies examining the effects of stress and social
      support on the academic achievement of Hispanic associate degree nursing
      students. The first study investigated stress, measured by the Life Experiences
      Survey (LES), and its relationship to academic achievement. Data analysis
      revealed a relationship between negative stress and academic achievement. Student
      level and ethnic origin were found to be predictive of stress. Ethnic origin and
      age also had an effect on academic achievement. Qualitative data indicated that
      students experienced stresses as a result of the academic environment. The second
      study investigated the effect of social support, measured by the Norbeck Social
      Support Questionnaire (NSSQ), on student persistence. No significant relationship
      was found. Qualitative data revealed less than desired social support in lower
      achieving students. Conclusions from these studies form the basis for
      identification of the high risk student and strategies to remediate the
      academically handicapped Hispanic student.

PMID- 9287592
TI  - Canadian transcultural nursing: applying the Giger and Davidhizar model.
AB  - Giger and Davidhizar (1995) provide a model for assessing clients from differing
      cultures in order to be aware of differences and to plan appropriate strategies.
      This model is appropriate for use with groups of individuals regardless of
      culture and is particularly useful and appropriate in Canada where society is a
      mixture of people from different ethnic backgrounds, different political and
      religious persuasions, and different aspirations. This paper presents an overview
      of the cultural diversity among Canadians and then applies the model as an
      assessment tool that can be used by Canadian nurses.

PMID- 9287594
TI  - Cultural diversity and today's managed health care.

PMID- 9287593
TI  - Relationship between social support, self-esteem and codependency in the African
      American female.
AB  - Increasing numbers of minorities are seeking mental health assistance. Inclusion
      of cultural considerations is important for increasing sensitivity to those whose
      life experiences differ. For African Americans, therapy is better facilitated if
      one operates from a cultural specific frame of reference. African American women
      attending a women's support group were surveyed. Questionnaires querying
      dimensions on family relationships, self-esteem and dependency were utilized.
      Results indicated a relationship between social support, self-esteem and
      codependency in African American females. Social support and self-esteem were
      inversely associated with codependency. This study provides insight for mental
      health professionals in counseling African American females.

PMID- 9287595
TI  - The cross-cultural applicability of Orem's conceptual framework.
AB  - This study examined the applicability of the Orem's Theory of Self-Care with
      Chinese clients. The central concepts included the universal self-care behaviors
      (USC), health-deviation self-care behaviors (HDSC), health, and the basic
      conditioning factors of adults with Type II diabetes mellitus. Basic conditioning
      factors (BCF) were internal or external factors that affected an individual's
      ability to engage in self-care bahaviors (Orem, 1991). This study used a
      descriptive correlation design. Orem's theory of self-care guided the selection
      of the variables and the hypothesized outcomes. Data were collected through phone
      interviews of 100 Chinese at Taiwan. The average age was 57.88 (SD = 12.41). A
      total of 51 items on questionnaires was used to measure self-care behaviors and
      health. An investigator developed a questionnaire assessing sociodemographic
      characteristics. Sixty-six percent of respondents perceived they lived with
      someone who helped too much and hindered their own diabetes-related self-care. A
      significant correlation was found between educational level and diabetes-related
      self-care behaviors. A significant correlation was also found between the
      educational level and the universal self-care behaviors. There were significant
      correlations among the universal self-care behaviors and diabetes-related self
      care; between the universal self-care behaviors and the perception of health;
      between the diabetes-related self-care behaviors and the perception of health.
      The findings implicated cross-cultural applicability of Orem's conceptual
      framework.

PMID- 9287597
TI  - Exploring cultural diversity.
AB  - "Exploring Cultural Diversity" and "Out of the Comfort Zone" are companion
      articles written from a professor's and student's perspective about experiences
      in transcultural nursing. The nursing professor describes the planning and
      implementation phases of the program, and the student describes the life-changing
      experiences and impressions which occurred. The theory portion of the program
      takes place at the university in the semester prior to the clinical segment, and
      the experiential component of the course includes traveling to, living, and
      practicing within a developing country. A journey to the Dominican Republic in
      1994 is recounted. Together the articles emphasize the need for increasing global
      understanding of the relationship of culture to health in order to promote high
      level wellness for all the citizens of this planet.

PMID- 9287596
TI  - A cultural values assessment tool.
AB  - Faculty members at a small liberal arts college teaching in a course entitled
      "Contemporary Cultures: China, Guatemala and Nigeria" found that using a cultural
      values assessment tool strengthened the course. This assessment tool was
      developed by a faculty member teaching in the course when no standardized tool of
      this type could be found. Students and faculty involved with this senior core
      course found the cultural values assessment tool to be effective in introducing
      the course, in stimulating some critical thinking throughout the course and in
      concluding the course.

PMID- 9287598
TI  - Out of the comfort zone.

PMID- 9287599
TI  - Critical thinking, health policy, and the Hmong culture group, Part II.
AB  - The Hmong are an Asian cultural group originating primarily in the northern hills
      of Laos. During the Vietnam conflict, they fought and died for the U.S. during a
      secret Laotian war. The U.S. gained their support in exchange for protecting them
      from their enemies in Laos regardless of the war's outcome. When North Vietnam
      took over Laos, hundreds of thousands of Hmong fled to Thailand's refugee camps;
      from there, over 100,000 Hmong refugees relocated to the U.S. (Heu, 1996). With
      them, the Hmong brought culture, language, and healthcare beliefs and rituals, as
      well as distinct challenges to U.S. communities, policy makers, and healthcare
      professionals. This article is the second in a two-part series on critical
      thinking and health policy and the Hmong culture group.

PMID- 9287600
TI  - Spirituality and aging.

PMID- 9287601
TI  - The Eating Behavior Scale. A simple method of assessing functional ability in
      patients with Alzheimer's disease.
AB  - Health care providers and family members need practical methods of assessing
      functional skills of individuals with Alzheimer's Disease (AD). There are
      neuropsychological tests that identify areas of function and dysfunction in the
      brain, but discrepancies have been noted between test scores and functional
      behaviors in activities of daily living (ADLs). The Eating Behavior Scale (EBS)
      was developed to measure functional ability during meals. A sample of 30 patients
      with probable AD were observed using the EBS during two meals on two different
      days. There was a strong negative correlation between meal duration and the EBS
      score. That is, the lower the EBS score, the longer the time required to complete
      the meol. Mini-Mental Status Exam (MMSE) scores were positively correlated with
      EBS scores. Patients with higher MMSE scores and less time since diagnosis tended
      to have higher EBS scores, indicating greater independence in eating.

PMID- 9287602
TI  - Quiet music. An intervention for mealtime agitation?

PMID- 9287603
TI  - Reporting elder mistreatment.
AB  - Elder mistreatment, defined as the abuse and neglect of older persons, includes
      physical, psychological, and sexual abuse, caregiver and self-neglect, and
      financial exploitation. Fifty states and the District of Columbia have passed
      legislation to establish adult protective service (APS) programs. State APS
      statutes authorize APS agencies to investigate cases of elder mistreatment. Some
      status fund services to alleviate the abusive or neglectful situation. This
      article analyzes the critical aspects of state-specific APS legislation affecting
      nursing practice with older adults and the nurse's role in reporting cases of
      elder mistreatment.

PMID- 9287604
TI  - The mealtime experience of a cognitively impaired elder: ineffective and
      effective strategies.

PMID- 9287605
TI  - Promoting physical activity in the senior years.

PMID- 9287607
TI  - Collaborating for our patients' well-being.

PMID- 9287606
TI  - What can nurses do about financial exploitation of elders?

PMID- 9287608
TI  - Planning for the future of long-term care: consumers, providers, and purchasers.
AB  - The number of consumers needing long-term care services, including nursing home
      care, will more than triple during the next 30 years, and their characteristics
      will change dramatically. Providers will be in short supply, and an increasing
      variety of professionals will participate in meeting the long-term care needs of
      the older population. Purchasers will make decisions about providing services
      based on the health-related outcomes and value of these services. While an
      integrated delivery system that incorporates a range of alternatives to the
      nursing home is the ideal, the demands and preferences of consumers, the
      availability of providers, and purchasers' mostly financially driven decisions
      will influence the achievement of such a system. The challenge to the nursing
      profession will be to continue to serve as an advocate for the patient as the
      system evolves and to provide data for wise policy decision-making.

PMID- 9287609
TI  - Inadequate staffing at mealtime. Implications for nursing and health policy.

PMID- 9287610
TI  - Payment incentives and conflicts of interest within a managed care environment.

PMID- 9287611
TI  - Managed care. What is its impact on nursing education and practice?
AB  - Market forces present the nursing profession with an urgency to prepare
      gerontological nurses to assume significant roles in the managed care industry.
      An understanding of the current managed care environment underscores the need for
      training. Nurses require a "managed care" skill-set encompassing a firm grasp of
      the organization, financing, delivery, and policy implications of managed care as
      well as advanced practice clinical skills and a sound business orientation. The
      importance of the consumer as a significant player in managed care is
      highlighted.

PMID- 9287612
TI  - A residential care alternative for elderly deaf persons.

PMID- 9287613
TI  - Geropsychiatry. Barriers to follow-up studies with the chronically mentally ill
      elderly in long-term care settings.

PMID- 9287614
TI  - The major increase in the number of older adults is big news today. How do you
      feel about being part of those statistics? Should you need nursing care, what is
      your expectation about how that care should be provided?

PMID- 9287615
TI  - Mentoring our young.

PMID- 9287616
TI  - The art of research participants in doing science.

PMID- 9287617
TI  - Experiences of the chronically ill. A covert caring for the self.
AB  - The biomedical paradigm of Western society has dictated the values, attitudes,
      and behaviors of many health care professionals. For people living with chronic
      illnesses, this biomedical domination has reduced client control. Because of the
      prolonged nature of chronic conditions, these clients often become the best
      experts on themselves; however, this is rarely recognized or respected by health
      care professionals. As a result, people living with chronic illnesses often go
      underground and engage in a covert caring for the self. Results of a recent
      research project highlight four themes that provide insight into these covert
      caring practices: (a) taking control, (b) seeking knowledge, (c) accessing
      alternate healing modalities, and (d) an altered relationship with health care
      providers. These findings provide nurses with an opportunity for increased
      awareness and sensitivity to the experiences of people living with chronic
      conditions. Such a sensitivity could lead to enhancing client autonomy.

PMID- 9287618
TI  - The experience of therapeutic touch for novice recipients.
AB  - This study explored the experience of receiving Therapeutic Touch (TT) from the
      point of view of recipients with no prior experience with TT. Eleven female
      graduate students who were part of a larger study were interviewed after the
      second of two TT sessions and statements from the transcripts were analyzed for
      words, phrases, or sentences that fell into one of five categories: (a)
      relaxation, (b) physical sensations, (c) cognitive activity, (d) emotional
      (feelings), and (e) spiritual/transcendent. All participants reported feeling
      relaxed and had physical sensations and cognitive activity during the TT
      sessions, and most of the statements fit into these categories. Fewer statements
      reflected emotional or spiritual experiences and not all participants had these
      experiences. The sensations associated with TT may occur developmentally.
      Initially, physical and cognitive experiences are identified. The deeper,
      meaningful sensations may occur after an individual has more experience with the
      intervention.

PMID- 9287619
TI  - Perimenopausal women's alienation.
AB  - A feminist perspective was used to interpret data gathered from perimenopausal
      women using hormonal replacement therapy. Silence was the most pervasive and
      disquieting theme. These women parroted biomedical cognizance and iterated little
      authentic expression of experience. This silence reflected the women's
      existential position of the double other, marginalized first by being a woman and
      second by reason of medical norms for women being based on reproductive function.
      This position of alienation is explored within the context of Western culture and
      the patriarchal values of rationality and science. Implications are drawn for
      holistic nurses to facilitate women's physical awareness and articulation of
      their personal experiences.

PMID- 9287620
TI  - Nursing and alternative medicine. Legal and practice issues.
AB  - The burgeoning interest in alternative medicine in the past decade has created a
      demanding health care climate for professional nursing. Rising consumer
      consciousness and the cost of traditional Western medicine have together
      influenced an environment in which individuals and payers seek low-cost, high
      value remedies. This article presents a definition of alternative medicine and an
      overview of related research initiatives. In addition, legal and practice
      considerations for professional nursing are discussed. The language of current
      nurse practice acts neither prohibits nor actively promotes alternative medicine
      practices. However, differences in the regulation of health care professionals,
      specifically physicians and nurses, create challenges for nurses as they respond
      to both consumer demand and the need for consumer protection, and work with
      physician colleagues in alternative medicine. Accompanying these challenges is
      the need to protect nurses' regulatory freedom and autonomy.

PMID- 9287621
TI  - Sexual risk behaviors among rural women of childbearing age.
AB  - Given the morbidity and mortality associated with sexually transmitted diseases
      and HIV/AIDS, the increasing number of HIV/AIDS cases among heterosexual women,
      and the limited information regarding rural women's health, it is timely to
      holistically examine the determinants of sexual risk behavior(s) among rural
      women of childbearing age. Use of the Interaction Model of Client Health Behavior
      allows an integrated perspective of demographic characteristics, motivation,
      problem-solving, self-esteem, and sexual risk behaviors for this population. The
      144 subjects in this study included 76 African American and 60 White women
      (average age 28.76 years, SD 6.58 years). Sexual risk behaviors were defined as
      more than one sex partner and (partner) not using a condom. African American
      women reported using condoms more than White women. Younger married women used
      condoms more than older married women.

PMID- 9287622
TI  - A lifeworld paradigm for nursing research.
AB  - This article is a companion to an earlier article entitled "Challenging a
      Reductionistic Paradigm as a Foundation for Nursing," which appeared in the
      December 1995 issue of the Journal of Holistic Nursing. The authors discuss how
      five concepts-encounter, openness, immediacy, uniqueness, and meaning-which
      constitute their philosophy for nursing practice, also comprise a foundation for
      human sciences research. In the first article, encounter was presented as the
      core concept for practice. In the present work, openness is the central idea in a
      lifeworld research paradigm, with encounter, immediacy, uniqueness, and meaning
      as supporting concepts. Openness is explicated with the notions of open
      mindedness, open-heartedness, phenomenological questioning, and preunderstanding.
      A lifeworld paradigm for research is based on phenomenological philosophy and the
      understanding that the conduct of research is guided by the researcher's openness
      to the phenomena of the everyday world.

PMID- 9287623
TI  - Prayer and healing. A case study.
AB  - This article examines the relationship between prayer and healing and its
      relationship to holistic health. The apparent healing that results from prayer
      mystifies researchers. Numerous theories may be offered as to the mechanism by
      which this healing occurs. The belief of the praying person in the power of the
      prayer itself may stimulate healing, as the placebo effect suggests. The
      relaxation response and the sense of self-efficacy gained through the act of
      praying may enhance the immune system. Despite these explanations of the
      mechanisms through which prayer promotes healing, there some-times exists a facet
      of prayer and healing that defies rational explanation and seems to suggest the
      existence of a higher power. A case is presented that explores assistance from a
      higher power as a potential explanation for the healing.

PMID- 9287624
TI  - An innovative teaching strategy for staff development departments. Olga and
      Bertha to the rescue.
AB  - Efforts to address facility-wide educational topics in one staff development
      department have resulted in the development of innovative strategies to reach the
      maximum number of nurses with the greatest positive outcome. We were faced with
      the challenge of trying to improve discharge planning. A random chart review
      completed by the hospital utilization coordinator showed an appalling lack of
      discharge planning on the part of most hospital nursing staff. How would we
      entice nurses to attend inservice programs concerning such a potentially "dry"
      topic? Enter Olga and Bertha Smith, two characters devised to inject humor and
      entertainment into the educational sessions. The characters were role played by
      the authors and videotaped to show a standard scenario that demonstrated the
      intricate discharge planning needs of a young single mother (Olga) and her
      dependent mother (Bertha). Evaluations revealed extremely positive feedback for
      the characters as an enjoyable and effective way of teaching. Since then, Olga
      and Bertha have attracted, entertained, and educated nurses about three
      subsequent inservice topics.

PMID- 9287625
TI  - The effects of inservice education on the institution of triage protocols.
AB  - This correlational study examined the effects of inservice education on the
      initiation of triage protocols by emergency room nurses for patients experiencing
      cardiac symptom distress. The study used a pretest/posttest design with a
      convenience sample of 40 patients who were experiencing cardiac symptom distress.
      Chart reviews were conducted on 20 patients seen in the emergency room with
      suspected myocardial infarction. Then emergency room nurses had an inservice
      program on institution of triage protocols, and 20 more patient charts were
      reviewed. The study revealed two statistically significant findings. First, the
      staff nurses incorporated pain and symptom distress measurement tools in physical
      assessments more frequently after inservice education sessions than before
      inservice education sessions. Second, the staff nurses documented the use of
      triage protocols more frequently after the inservice education sessions than
      before the sessions. These findings suggest that nursing inservice education
      positively affects nursing care for patients with suspected myocardial
      infarction.

PMID- 9287626
TI  - Action research applied to a preceptorship program.
AB  - In this article the authors describe the development of a framework designed to
      discuss expectations between preceptors, orientees, nursing unit managers and
      clinical nurse educators. Action research theory provided the framework for this
      process. Preceptors found the process of articulating expectations helpful,
      relevant, and meaningful to their practice.

PMID- 9287627
TI  - The effect of peer review on professionalism, autonomy, and accountability.
AB  - In this article, the authors describe the relevance and impact of peer review on
      professional nursing practice. The healthcare, business, education, and social
      science literature are reviewed. Although the benefits of peer review often are
      assumed to contribute to increased professionalism, autonomy, and accountability,
      there is little formal research evidence to support these assumptions.
      Regardless, empirical data show potential for increased professionalism, improved
      performance, and valuable feedback provided to nursing personnel. In addition,
      the authors explore the potential of peer review in developing and maintaining
      professional accountability among practicing staff nurses.

PMID- 9287629
TI  - An investigation into modification of personality hardiness in staff nurses.
AB  - Responsibilities of nurse educators include assisting nurses to adjust to a
      rapidly changing healthcare environment and demonstrating how these efforts are
      effective. In this article, the authors describe a study that measures the
      effects of teaching hardiness, a characteristic encompassing commitment, control,
      and challenge, to newly employed hospital nurses. The authors believe the study
      results indicate that instruction in hardiness is possible and may have an impact
      on morale.

PMID- 9287630
TI  - Transcultural nursing. A source guide.
AB  - The concept of transcultural nursing is relatively new to the nursing literature.
      It had been less than 30 years since Madeleine Leininger first began to develop a
      theory of transcultural nursing as part of a doctoral study in anthropology. Much
      has changed in that time, and nursing staff development and inservice educators
      need to provide educational offerings within a multicultural context in a timely
      manner. Cultural diversity is the standard in the mid-1990s, and those nursing
      staff development programs that are sensitive to this fact produce employees with
      advantages over those from settings that do not prepare staff for practice in a
      constantly changing world. This annotated bibliography about transcultural
      nursing details key references for staff development and inservice programs. It
      is not intended as an exhaustive review but rather focuses on the most relevant,
      timely, and useful of the ever increasing number of publications concerning this
      important subject. Six major books and four of the most pertinent recent journal
      articles are included. Conclusions and implications for nursing staff educators
      are offered.

PMID- 9287628
TI  - Development of a Code Blue Protocol test.
AB  - The purpose of this project was to develop a test to evaluate knowledge of the
      Code Blue Protocol at St. John's Regional Health Center. In critical care and
      telemetry units, the registered nurses are required to pass a yearly test
      concerning the Code Blue Protocol. The content of the test was based on the
      nursing service policy containing the Code Blue Protocol. The test was based on
      content items deemed very important by nursing directors. A panel of experts in
      education and critical care reviewed the test. A pilot administration of the test
      occurred in January 1994. Any item with a 50% pass/ nonpass was examined by the
      panel of experts; their feedback was used to modify those test items. The test
      was administered to the population of registered nurses in March 1994.

PMID- 9287631
TI  - Simulation game: a tool for staff development and its effects on staff behavioral
      outcomes.

PMID- 9287632
TI  - Hospital-community job exchange: an innovative nursing staff development
      experiment.

PMID- 9287634
TI  - Reflections on the art and science of perianesthesia nursing.
AB  - The 21 words that form the basis for this article were selected because they
      convey the art and science of perianesthesia nursing practice, place
      perianesthesia nursing in both a national and global context, and facilitate
      reflection about this specialty practice. Reflection can lead to affirmation or
      change and perhaps even a design for the future.

PMID- 9287633
TI  - The T bag.

PMID- 9287635
TI  - Practice characteristics of the dual certificant--CPAN/CAPA.
AB  - Little information is available regarding the practice of nurses who hold two
      perianesthesia certification credentials (CPAN/CAPA) and their motivation in
      achieving a dual certification distinction. Achievement of certification in both
      areas of perianesthesia nursing is a significant accomplishment. Nurses with dual
      certification are a valuable asset to the profession, their employer, and the
      perianesthesia patient. The characteristics of this unique group were surveyed by
      the American Board of Perianesthesia Nursing Certification, Inc. The findings
      have implications for nurse managers, educators, and perianesthesia colleagues.

PMID- 9287636
TI  - Obstetrical patient postanesthesia management protocol.
AB  - There is current evidence that maternal surgery, ie, surgery performed during
      pregnancy (for any reason) and requiring an anesthetic, is associated with
      increased perinatal morbidity and mortality rates. The "Obstetrical Patient
      Management Protocol" details the behaviors and actions required by the
      postanesthesia nurse in providing quality care for the pregnant patient requiring
      surgery and/or anesthesia that is related or unrelated to her pregnancy.

PMID- 9287637
TI  - Chicken feet: Part two.
AB  - This article is the second part of the story of a trip taken by the author to
      Guatemala, Central America in 1996. It was a part of Operation Kids, which is
      sponsored by the Christian Children's Fund in Richmond, VA. The author and her
      fellow medical staff represented the Plastic Surgery Division of the Medical
      College of Virginia Hospitals.

PMID- 9287638
TI  - Neuromuscular relaxation and reversal: an update.
AB  - Neuromuscular relaxants are commonly used in the provision of general anesthesia
      for the majority of surgical procedures. After a brief overview of the physiology
      of the neuromuscular junction, pharmacology of both depolarizing and
      nondepolarizing muscle relaxants will be discussed. Attention will be given to
      side effects and factors that influence neuromuscular blockade including reversal
      agents. This article will provide the PACU nurse with the knowledge necessary to
      provide safe and effective nursing care.

PMID- 9287639
TI  - Designing research survey design--Part one.
AB  - Surveys are essential for discovering the incidence, distribution, and
      interrelationship of variables within a population. As such, it is important that
      we are able to critically read published surveys. This manuscript is the first of
      two dealing with survey research. Sampling and external validity are covered in
      this manuscript.

PMID- 9287640
TI  - Practical points in the management of the hospitalized epileptic patient.
AB  - This article briefly discusses the etiology and pathophysiology of epilepsy.
      Therapeutic management and nursing considerations of the hospitalized epileptic
      patient are the primary focus.

PMID- 9287642
TI  - Putting principles into practice.

PMID- 9287641
TI  - Learning to learn: step one for survival in the new paradigm.
AB  - New challenges require new approaches and many of the suggested solutions are in
      conflict with how we were taught in our formative years. Team work in high school
      and college was mostly found in sports-related activities. Collaboration in a
      classroom was not encouraged and could be viewed as cheating. We did not learn to
      share knowledge in a group nor to group problem solving, yet we are told that
      those are the very skills we need to have to survive in today's workplace. The
      first step to success is to look at how we were taught to learn and make the
      shift to learning in a different manner.

PMID- 9287643
TI  - Restrictive practice environment and nurse practitioners' prescriptive authority.
AB  - This study analyzes the impacts of several variables, including a restrictive
      practice environment, on a nurse practitioner's level of autonomy with respect to
      prescribing selected categories of medicines. A general linear model is applied
      to data from the 1992 national sample of nurse practitioners. Results show that
      among the significant independent variables, a restrictive environment of imposed
      state laws and regulations reduces nurse practitioners' level of autonomy in
      prescribing medications and acts as a barrier to their practicing to full
      potential. Results and policy implications are discussed.

PMID- 9287644
TI  - Family stress theory: implications for family health.
AB  - The Resiliency Model of Family Stress, Adjustment and Adaptation explains
      variations in how families respond to stressful situations and crisis. Key
      concepts of the model and supporting research are presented. Suggestions for ways
      to use the Resiliency Model in practice are provided. This article demonstrates
      the value of theory-based nurse practitioner practice by describing how
      assessment and interventions based on the Resiliency Model can assist the family
      nurse practitioner in supporting and guiding a family in crisis.

PMID- 9287645
TI  - Commercial services and women's health on the information superhighway.

PMID- 9287647
TI  - Evaluation and management of primary nocturnal enuresis.
AB  - Enuresis can be a source of family crisis, and can contribute to a lack of self
      esteem in the affected child. It must be stressed to both parent and child that
      improvement is gradual and largely a function of maturation in cases where no
      organic problem is identified. Research shows that many enuretic children seem to
      have small bladder capacities (Long, 1991), and that the majority have a polyuric
      factor such as a decreased level of AVP that is amenable to replacement therapy
      with desmopressin (Bloom, 1993; Hamburger, 1993; Hjalmas & Bengtsson, 1993;
      Norgaard & Djurhuus, 1993). Utilizing pharmacologic treatment can accelerate
      spontaneous cure or act as a substitute until time provides nocturnal continence
      (Norgaard & Djurhuus, 1993). Nurse practitioners can use multiple modalities in a
      holistic approach to reframe this problem and to involve children in solving
      their own problem. The child who is given a basic understanding of the physiology
      involved in the healing process will be able to identify inner healing resources
      and utilize external resources available to him or her. This approach begins with
      children's imaging the desired outcome of urinary control and ends with achieving
      increased self-esreem and the sense of competence they deserve.

PMID- 9287648
TI  - Donald Weaver, MD, National Health Service Corps: celebrating 25 years of care to
      the underserved. Interview by Carol Jennings and Jan Towers.

PMID- 9287649
TI  - Quick Reference Guide for Clinicians. Early identification of Alzheimer's disease
      and related dementias. U.S. Department of Health and Human Services.
AB  - This Quick Reference Guide for Clinicians contains highlights from Recognition
      and Initial Assessment of Alzheimer's Disease and Related Dementias, Clinical
      Practice Guideline No. 19, which was developed by a multidisciplinary panel
      composed of health care professionals and consumer representatives. The Quick
      Reference Guide focuses on (a) symptoms that suggest the presence of a dementing
      disorder and (b) steps to follow in conducting an initial assessment for
      Alzheimer's disease or a related dementia, including use of specific mental and
      functional status tests on the basis of their efficacy and clinical utility in
      discriminating early-stage dementia. It also addresses how to interpret test
      results, the role of neuropsychological testing, and resources for patients and
      families facing a diagnosis of probable dementia.

PMID- 9287646
TI  - Blood pressure. US Public Health Service.

PMID- 9287650
TI  - Impacting maternal and child nutrition in rural Vietnam: experiences of an
      American nurse-consultant.
AB  - This article describes a pilot project undertaken by the author, her physician
      husband and a Vietnamese physician partner in a rural Vietnamese community on the
      Mekong Delta approximately 80 kilometers from Saigon. The project was focused on
      reducing malnutrition in a community of approximately 11,000 people. Successful
      steps were taken, based on earlier research, to help the members of this rural
      community to get involved in developing a solution for maternal and infant
      malnutrition in their community.

PMID- 9287651
TI  - Psychotropic prescriptive patterns among nurse practitioners in nonpsychiatric
      settings.
AB  - This study explores mental health care treatment among primary care nurse
      practitioners. Forty-two nurse practitioners from a variety of specialty practice
      areas responded to a questionnaire focusing on mental health care management in
      their practice setting. Results showed that 95% of the nurse practitioners
      encountered clients with mental illness in their practices. The most common
      psychiatric disorders seen among the nurse practitioners were depression and
      anxiety disorders. Attention deficit/hyperactivity disorder was the most
      frequently encountered mental illness among the pediatric nurse practitioners.
      Bipolar disorder and schizophrenia were also encountered by nurse practitioners
      in a variety of settings, though with less frequency. Seventy-six percent of the
      nurse practitioners reported prescribing psychotropic medications. Details of the
      nurse practitioners' prescriptive patterns are described. Recommendations for
      further research are discussed, and the need for continuing education in
      psychopharmacology among primary care nurse practitioners is highlighted.

PMID- 9287652
TI  - Assessment of body composition in the healthy adult.
AB  - Information obtained from body composition assessment can provide a foundation
      for the development of weight-loss and exercise guidelines. The ideal method for
      assessing body composition in the clinical setting should be relatively
      inexpensive, as convenient as possible for the individual, reproducible and
      accurate, and helpful in evaluation considerations (Lohman, 1992). It appears
      that skinfold thickness measurements could have specific advantages in the
      clinical setting when compared to bioelectrical impedance and traditional methods
      of using height and weight. Ideally, body composition assessment should be an
      integral component of the physical examination of the healthy adult.

PMID- 9287653
TI  - Driving and the elderly.

PMID- 9287654
TI  - Today's health care news on the information superhighway.

PMID- 9287655
TI  - Lung cancer.
AB  - The primary prevention of lung cancer is to avoid and decrease the use of
      tobacco. Further research could include studying the effects of culture,
      ethnicity, and geographic location on smoking. Education needs to start early in
      the educational systems. At present there are programs for primary grades on drug
      and alcohol abuse and how to say "no." Education also needs to include the family
      when the parents are smokers, as their children are exposed to second-hand smoke
      and are led by example. Certain religious groups believe it is their duty to keep
      healthy and, therefore, do not smoke. These groups may be able to provide some
      answers as to how to prevent people from smoking. Prevention--it is our real
      hope.

PMID- 9287656
TI  - The importance of culture in the provision of midwifery care.

PMID- 9287657
TI  - Chinese zuo yuezi (sitting in for the first month of the postnatal period) in
      Scotland.
AB  - OBJECTIVE: To examine how Chinese women experience postnatal care in a Scottish
      setting, their beliefs, needs and experience, and why any differences exist. The
      aim is to bring the knowledge forward and to improve these women's childbearing
      experience. DESIGN: a qualitative comparative approach. SETTING: maternity units
      in Scotland. PARTICIPANTS: ten Chinese and ten Scottish women, ten health
      workers, five relatives, five Chinese women's friends, and five Scottish women's
      friends, plus two groups discussions of four and six Chinese discussants, and one
      group discussion with four Scottish mothers and a health worker. METHOD: four
      stage semi-structured interviews with the two comparison groups of ten Chinese
      and ten Scottish women, and non-structured interviews/talks/discussions with ten
      health workers, ten women, five relatives and ten friends. FINDINGS: zuo yuezi is
      a popular integrated set of postnatal practices for Chinese mothers, not only in
      China, but also in Scotland, in their convalescence after giving birth. This
      traditional postnatal behaviour is embedded in culture. It is used to facilitate
      the physical recovery of the mothers, to prevent chronic illness, and also to
      strengthen their intra-family relationships. CONCLUSION: zuo yuezi serves as a
      physical convalescence, a preventative measure, a social sanction to rest, a
      consolation, and a prompt for Chinese women to concentrate on their baby and
      their role of breast feeding, as well as an occasion to strengthen the intra
      family tie, especially between the woman and her own mother or mother-in-law.
      This practice has a direct bearing upon the psychological well-being of Chinese
      women postnatally and in their future life. This suggests that these puerperal
      practices and the custom deserve the cognitive recognition of midwives, so that
      they can be aware of and respect the indigenous beliefs and practices that link
      the events of childbearing, the health status of women, and family relationships
      in order to provide better maternity care for this group of women.

PMID- 9287658
TI  - Hong Kong Chinese women's perception of support from midwives during labour.
AB  - OBJECTIVE: to identify what support from midwives  hinese women find most helpful
      in contributing to a positive labour and childbirth experience. DESIGN: a
      quantitative study using a cross-sectional design was employed. Data were
      collected using a Chinese language version of the Bryanton Adaptation of Nursing
      Support in Labor Questionnaire. SETTING: a postnatal ward in a Hong Kong public
      hospital. PARTICIPANTS: purposive sample of 30 Hong Kong Chinese women, from 24
      to 38 hours after delivery. KEY FINDINGS: the category of 'informational support'
      with the specific behaviour of 'praise' was identified as the most supportive.
      Tangible support such as 'touching' was considered the least helpful behaviour.
      IMPLICATIONS FOR PRACTICE: suggestions are made for promoting culturally
      sensitive midwifery care for Chinese women to include: 'saving face';
      interpreting personal orientation; and supporting Chinese 'hot and cold' beliefs.

PMID- 9287659
TI  - Elderly nulliparae in midwifery care in Amsterdam.
AB  - OBJECTIVE: to compare labour complications, after an uncomplicated pregnancy, of
      first births in women 35 years and older with women 20-30 years old. DESIGN: an
      explorative prospective cohort study. SETTING: four independent midwives'
      practices in Amsterdam. PARTICIPANTS: a group of 49 elderly nulliparae was
      compared with a group of 99 younger nulliparae. MEASUREMENTS AND FINDINGS:
      percentage of referrals and reasons for referral during pregnancy and labour,
      mode of delivery and obstetric outcome. KEY CONCLUSIONS: no significant
      differences in referrals were found between the two compared groups. Obstetric
      outcome was not different between the groups, except for a lower birthweight in
      the elderly group. A trend is seen for a raised percentage of referrals during
      labour in the older group. This is almost completely explained by a failure to
      progress during first and second stages of labour. Related to this was a trend
      for an increased incidence of caesarean section in the older group of women.
      IMPLICATIONS FOR PRACTICE: after selection, the elderly nullipara, under the care
      of a midwife, does not have an increased risk of fetal distress or other
      emergency factors compared to the younger nullipara. However, the referral rates
      during labour, both of younger and older women, are high.

PMID- 9287660
TI  - The experience of labour: using ethnography to explore the irresistible nature of
      the bio-medical metaphor during labour.
AB  - OBJECTIVE: taking evidence provided by an ethnographic study based on women's
      experiences of pregnancy and childbirth, and using ritual theory in the analysis
      of the relationship between the medical metaphor, inherent in contemporary birth
      settings, and the views and expectations of childbirth which the women bring with
      them to that setting. DESIGN: small scale qualitative study using ethnographic
      research techniques. SETTING: GP surgeries, two consultant-led, hospital-based
      antenatal units, labour suites and postnatal wards, plus the homes of the women
      involved from the north east of England. PARTICIPANTS: 40 primigravid women
      providing two sample groups. Half of the women were actively involved in
      antenatal class programmes run by the National Childbirth Trust and the NHS and
      the other half did not attend any antenatal classes. MAIN FINDINGS: within the
      sample there was a clear cultural diversity which carried significant
      implications on how the women assembled their understanding of pregnancy and
      birth antenatally. However, this division lost clarity at the onset of labour,
      rendering delivery experiences more similar than might have been expected. Ritual
      theory offers significant insight into this phenomenon, analysing birth as a rite
      of passage provided a necessary tool to explain why this pattern emerged in the
      data. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: cultural diversity suggests
      an element of caution should be used when advocating the notion of 'informed
      choice' across the board, sensitivity to existing cultural values is imperative.
      Despite an emphasis on informed choice, midwifery practice continues to offer the
      medical metaphor as the dominant cultural prop in the labour ward.

PMID- 9287661
TI  - Challenges of clinical learning for student midwives.
AB  - OBJECTIVE: to identify factors which affect the learning of clinical skills by
      student midwives. DESIGN: ethnographic, grounded theory. SETTING: a large urban
      maternity hospital and its community area in the south of England. PARTICIPANTS:
      student midwives, midwives, midwifery managers and teachers. DATA COLLECTION: by
      observation in clinical settings and interviews. KEY CONCLUSIONS: observation,
      indirect learning and trial and error were the strategies used by midwives and
      students in order to obtain competency in clinical skills. However, anxiety,
      because of inadequate instruction and supervision and poor communication,
      interfered with learning and students felt ill prepared to function as midwives.
      IMPLICATIONS FOR PRACTICE: clinical midwives need to be educated to facilitate
      the transfer of theoretical learning into clinical practice, and teachers need to
      re-learn the experience of being a clinical midwife.

PMID- 9287662
TI  - Community midwives' and general practitioners' perspectives, of antenatal care in
      the community.
AB  - OBJECTIVE: to ascertain who was providing antenatal care in the community in a
      defined geographical area in the north of England, and whether the care could
      achieve the government objectives presented in Changing Childbirth (DoH 1993).
      DESIGN: a questionnaire was used to obtain demographic information and semi
      structured interviews were held with care providers in order to assess the
      perspective of those providing care. PARTICIPANTS: a purposive sample of nine
      community midwives and six general practitioners (GPs). FINDINGS: the midwife was
      the professional undertaking most of the antenatal care although in most
      instances there was a GP available on site if required. GPs saw the midwife as
      the main provider of care with themselves as 'back up'. Conflict over
      responsibility for care was an issue in some instances. Whilst changes in
      antenatal care provision had been, or were about to be made, only one midwife
      expressed a clear positive feeling towards midwife-led care. Giving women the
      opportunity for choice provoked an overwhelming feeling of helplessness for
      midwives. Midwives and GPs believed their education adequately prepared them to
      provide antenatal care in the community, however, GPs did not attend regular
      updating sessions. IMPLICATIONS FOR PRACTICE: whilst it was recognised that
      midwives are taking increasing responsibility for antenatal care, GPs still
      believe that overall responsibility lies with them; therefore, there is a need to
      clarify roles. The majority of midwives expressed reservations about midwife-led
      care.

PMID- 9287663
TI  - Care of the perineum in the second stage of labour: a study of views and
      practices of Australian midwives.
AB  - OBJECTIVES: to seek the views of midwives on the practices related to the
      perineum in the second stage of labour; to identify predictors of their practices
      and to identify their actual practices in the second stage of labour, prior to a
      randomised trial of second stage perineal massage. PARTICIPANTS AND SETTING:
      independent midwives in South Australia and 194 midwives working in the delivery
      suites and birth centres of seven public hospitals in four states of Australia.
      DESIGN: midwives were surveyed using a questionnaire which sought their views on,
      and practices relating to, second stage perineal massage, delivery of the head
      and reasons for cutting an episiotomy. FINDINGS: one third of the respondents
      'never' practised perineal massage in the second stage of labour, 43% were
      'undecided' as to its value and 19% disagreed with the practice. Over half agreed
      that its use should be decided by the woman and her partner. When invited to
      select the five statements they most agreed with, and the five they most
      disagreed with, out of a possible 24, equal numbers (26%) were for and against
      the statement referring to such massage as helping to stretch the perineum and
      prevent tearing. More than half (55%) disagreed with the statement which
      predicted they would find the practice distasteful, while only 1.6% agreed with
      this statement. During delivery of the head, 71% of respondents attempted some
      form of flexion. There was 100% agreement that fetal distress almost always or
      frequently was an indication for cutting an episiotomy. CONCLUSIONS: there is
      little evidence from randomised trials to support many of the second stage
      practices, and further research will clarify those which are most effective. This
      sample of midwives demonstrated considerable variation in their views on, and
      practices in, the second stage of labour. Although one-fifth disagreed with the
      practice of second stage perineal massage, and 40% agreed that the midwife should
      decide, more than half (57%) believed it was a matter of choice for the woman and
      her partner. All were supportive of episiotomy use for fetal distress.

PMID- 9287664
TI  - Comment ... will you vote?

PMID- 9287665
TI  - RCM 115th annual conference in Harrogate.

PMID- 9287666
TI  - The mechanisms involved in the initiation of term labour.

PMID- 9287667
TI  - The 'little brown book'.

PMID- 9287668
TI  - Termination of pregnancy: Scotland, England and Guernsey.

PMID- 9287669
TI  - Routine iron supplementation--is it necessary?

PMID- 9287670
TI  - The use of actresses in midwifery education.

PMID- 9287671
TI  - The Miscarriage Association.

PMID- 9287672
TI  - Delegation of specialized health care services: using unlicensed assistive
      personnel in the school setting.

PMID- 9287674
TI  - New position statement. Regulations on bloodborne pathogens in the school
      setting. National Association of School Nurses, Inc.

PMID- 9287673
TI  - Anaphylactic shock--a personal experience.

PMID- 9287675
TI  - New core indicator data shows continued improvement in URRs, Kt/Vs. Nutrition,
      blood pressure values unchanged.

PMID- 9287677
TI  - Traveling with ESRD. Bon voyage.

PMID- 9287676
TI  - The shifting winds of renal care. Part I.

PMID- 9287678
TI  - Traveling with ESRD. Ain't no mountain high enough.

PMID- 9287679
TI  - Traveling with ESRD. On the road again.... Part I.

PMID- 9287680
TI  - Issues in Vascular Access. Improving outcomes in the face of managed care and
      capitation: one surgeons perspective.

PMID- 9287681
TI  - A facility guide to termination of dialysis services.

PMID- 9287682
TI  - Potential impact of "no-show" ESRD treatments on hospitalization.

PMID- 9287683
TI  - The kidney/pancreas transplant: an alternative for type I diabetics.
AB  - Whole pancreas transplantation is becoming a real and safe option for treatment
      of type 1 diabetic patients. Several controversial issues are still waiting for
      answers. Portal drainage has been reported to be a possible alternative to
      systemic drainage, but no prospective data comparing the two techniques is
      available yet. Further data comparing enteric and bladder drainage is also
      overdue. With new immunosuppressive agents, isolated pancreas transplantation may
      also gain better survival and wider application.

PMID- 9287684
TI  - Getting the most from your database: some basics for nephrologists.

PMID- 9287685
TI  - From fee-for-service to capitation: factors driving ESRD reimbursement system
      change.

PMID- 9287686
TI  - A plan for improving outcomes for patients with chronic renal failure.

PMID- 9287687
TI  - "Freedom of choice" argument may end shielding ESRD from managed care.

PMID- 9287688
TI  - Traveling with ESRD. On the road again... Part II.

PMID- 9287689
TI  - Litigation moves ahead in Alabama "old dialyzer" case.

PMID- 9287690
TI  - Reviewing the draft NKF-DOQI guidelines. 1. National Kidney Foundation-Dialysis
      Outcome Quality Initiative.

PMID- 9287691
TI  - Nutritional guidelines for infants and pediatric patients on peritoneal dialysis.

PMID- 9287692
TI  - Study: low transplant referral rate in NJ linked to few programs, patient
      education.

PMID- 9287693
TI  - A look at potential ESRD treatment alternatives for the future. Daily home
      hemodialysis.

PMID- 9287694
TI  - Shrinking resources and the growing ESRD population.

PMID- 9287695
TI  - Rediscovering long duration hemodialysis.

PMID- 9287696
TI  - On the front lines: a nursing perspective of managed care in the renal unit.

PMID- 9287697
TI  - Higher use of fistulae, improved surveillance key to reducing vascular access
      complications. National Kidney Foundation-Dialysis Outcomes Quality Initiative.

PMID- 9287698
TI  - An exercise program for CAPD patients.

PMID- 9287699
TI  - Renal physicians get managed care update.

PMID- 9287700
TI  - Capitation of ESRD services: when, where, why, how?

PMID- 9287701
TI  - Identifying potential organs for procurement: AOPO's death record review project.

PMID- 9287702
TI  - Kidney/pancreas transplants: worth the risks?

PMID- 9287703
TI  - A look at potential ESRD treatment alternatives for the future. The bioartificial
      kidney.

PMID- 9287704
TI  - MegaProviders forming partnerships to protect "specialized" care for ESRD
      patients.

PMID- 9287705
TI  - Beyond the MegaProviders. Other approaches to providing renal care.

PMID- 9287706
TI  - Issues in peritoneal dialysis. Adequacy, initiating dialysis, patient selection.
      National Kidney Foundation-Dialysis Outcomes Quality Initiative.

PMID- 9287708
TI  - Licensing dialysis facilities in Texas--a review.

PMID- 9287707
TI  - A review of worldwide use of patient questionnaires in dialysis.

PMID- 9287709
TI  - Movement to gospel music: an alternative therapy for nursing home residents.

PMID- 9287710
TI  - Creating solutions to an ethical dilemma.

PMID- 9287711
TI  - Oral exams: an alternative evaluation method.

PMID- 9287712
TI  - A solution-focused approach to help high-risk students.

PMID- 9287714
TI  - Opportunities for research in nursing education.

PMID- 9287713
TI  - Improving teaching effectiveness: facilitating student feedback.

PMID- 9287715
TI  - From hospital to home: a teaching and learning strategy.

PMID- 9287716
TI  - Unfolding cases: an experiential learning model.
AB  - The focus of education has changed from teaching to learning. This educational
      model stresses student outcomes that include critical thinking, effective
      communication, and students' ability to reflect their own learning. This article
      describes "unfolding cases," a comprehensive plan of learning that allows student
      practice time to solve individually and collectively problems they may encounter
      in clinical situations. It combines a variation and extension of the frequently
      used strategy of case study with multiple cooperative learning strategies,
      culminating in an individual reflective writing experience.

PMID- 9287717
TI  - Teaching nursing in a developing country.
AB  - Cultural competence is expected of nurses and educators in transcultural
      relationships. The author describes the Ugandan setting, where she taught
      registered nurse students for 9 months, and her process of assimilation leading
      to cultural competence. Concepts and issues pertinent to the acculturation of a
      nurse educator into international nursing in a developing country are discussed.

PMID- 9287718
TI  - A program evaluation approach to drug administration education.
AB  - To evaluate the education of undergraduate nursing students in drug
      administration, the faculty of La Salle University School of Nursing structured a
      program evaluation plan using a curriculum map. Faculty track the cognitive,
      affective, and psychomotor skills involved in drug administration. For example,
      all clinical nursing courses and the pharmacology course contain dosage and
      intravenous solution calculations in didactic material and tests. Program
      evaluation of the outcomes of medication administration education is continuous
      throughout the curriculum.

PMID- 9287719
TI  - Health promotion in a museum: a collaborative community partnership.
AB  - A collaborative community health education project connecting a science and
      history museum and a university school of nursing is described. This highly
      successful partnership connected senior community health nursing students with
      public education programs of the museum that focused on human body functioning,
      health promotion, risk reduction, and disease prevention. This project serves as
      a model for various other educational partnerships, including programs in the
      sciences, arts, humanities, and history.

PMID- 9287720
TI  - The personally perceived problem technique: enhancing clinical instruction.
AB  - Critical and creative thinking skills are essential when addressing health needs
      of patients in the rapidly changing health care arena. The personally perceived
      problem technique, an instructional tool based on the inquiry learning
      philosophy, can be used to refine critical and creative thinking skills in the
      clinical setting. The author discusses this unique instructional tool along with
      the role of the instructor.

PMID- 9287722
TI  - The transition to active learning: a lived experience.
AB  - As a guide for faculty initiating active learning strategies, the authors
      describe the transition from teaching by traditional lecture to an active
      learning approach in an introductory pharmacology course. Reasons for the
      transition are identified along with factors to consider related to faculty,
      students, course content, and resources. Appropriate activities are discussed,
      and a description of activities used successfully in this course is given.

PMID- 9287721
TI  - Integrating management concepts into licensed practical nurse and associate
      degree in nursing student clinical experiences.
AB  - In an associate degree nursing program in which students have the option to take
      the practical nurse licensing examination at the end of the first year,
      management concepts and experiences are introduced during the second semester.
      Many students work as licensed practical nurses and are expected to manage care
      for groups of clients. Using this model, students work together to practice time
      management and leadership skills.

PMID- 9287723
TI  - Education and bonhomie at Jalandhar. A report on XVII S.N.A. Biennial Conference.

PMID- 9287724
TI  - Supervision--a key to successful administration.

PMID- 9287725
TI  - Dengue fever. Some basic facts.

PMID- 9287728
TI  - Aspects of nursing education and the new approaches. A report on panel discussion
      at XVII SNA Biennial Conference.

PMID- 9287727
TI  - Status report on recommendations of High Power Committee on Nursing and Nursing
      Profession. Government of Florida.

PMID- 9287726
TI  - Management skills in nursing--quality patient care. The vital factors.

PMID- 9287729
TI  - A glossary of managed care terms.
AB  - With health care changing by the nanosecond and managed care entities growing,
      mixing and mutating even more quickly, the words used to describe, distinguish
      and categorize various entities and activities are confusing even the most
      sophisticated professionals. This "article" provides a much-needed dictionary of
      managed care terms.

PMID- 9287730
TI  - The phases of managed care: where does subacute care fit?
AB  - There are four phases of development in managed care based on their degree of
      market penetration: Phase I = up to 10%; Phase II = 11% to 30%; Phase III = 31%
      to 50%; and Phase IV = 50%+ of the market. Negotiation strategies vary according
      to the phase the market is in.

PMID- 9287731
TI  - Manage authorizations to manage care.
AB  - Managed care organizations rely on different ways to authorize the utilization of
      hospital services, physician specialty care and other referral services. Critical
      differences revolve around the role the primary care physician plays in the
      authorization process. The more tightly managed the system, the more likely
      unnecessary medical costs will be avoided.

PMID- 9287732
TI  - Medicare's point-of-service.
AB  - Guidelines recently issued by the Health Care Financing Administration (HCFA)
      explicity allow health maintenance organizations (HMOs) with a Medicare risk
      contract to sell a point-of-service (POS) benefit to their Medicare members. For
      an additional charge, these HMO members will now be allowed to go out-of-network
      for certain medical services.

PMID- 9287735
TI  - Competence: the shot heard around the nursing world.
AB  - In this column, the Joint Commission on Accreditation of Healthcare Organizations
      (JCAHO) addresses the issue of competence, how it is documented and the areas in
      which staff must demonstrate competence. Readers are urged to send in any
      questions they may have and JCAHO staff will answer them.

PMID- 9287733
TI  - Monitoring managed care's quality.
AB  - The Health Plan Employer Data and information Set (HEDIS) relies on over 60
      quality indicators divided into five categories to measure a health plan's
      performance. In 1995, the National Committee for Quality Assurance issued "report
      cards" for 21 health plans participating in its pilot project. The Health Care
      Financing Administration also will be measuring quality among the managed care
      organizations providing care to Medicare patients.

PMID- 9287736
TI  - Removing the confusion about infusion.
AB  - There is more to infusion technology than simply connecting the "pump-du-jour" to
      the central line. The purpose of infusion technology, its safety products and
      four categories of devices-elastomeric, mechanical, gas and membrane-are
      discussed.

PMID- 9287737
TI  - Labor law update--Part 2.
AB  - As a nurse moves away from the patient's bedside, the liability exposure for
      malpractice decreases. However, the nurse who moves into a management position
      faces another kind of liability-one regarding disciplinary actions such as
      employee terminations.

PMID- 9287738
TI  - State regulation in a world of "boundary-less" technology.
AB  - Today's technology links health care providers and patients across town, in the
      next state or even another country. Nursing across state lines poses
      complications: state-bound regulatory and licensure issues.

PMID- 9287739
TI  - Latest Medicaid managed care plans.
AB  - Several states are now studying ways to transfer aged and disabled Medicaid
      recipients to managed care plans. The most ambitious initiatives call for broad
      changes that integrate the financing and delivery of acute and long-term-care
      services. Greatly complicating matters is the fact that most of these recipients
      are also entitled to Medicare benefits. Unsustainable ballooning budgets make
      solutions imperative.

PMID- 9287740
TI  - Business strategies in subacute care.
AB  - To increase market share in a managed care environment, subacute care providers
      must confront several issues: business strategies, information technology and
      human resource management. The backbone of the subacute care facility is its
      human resources, its link to the world is information technology and its
      foundation is the business plan.

PMID- 9287741
TI  - Evaluating the performance of the APN.
AB  - Evaluation is the process of delineating, obtaining and providing useful
      information for judging decision-making alternatives. This article presents
      several models of evaluation and reviews the application of those models to
      advanced practice nursing.

PMID- 9287743
TI  - The future perioperative role.
AB  - Technology will be the engine driving high speed changes in surgery. To remain
      viable, perioperative nurses will need more advanced education and expanded
      activities outside the clinical setting. A more technologically-driven specialty
      may be at odds with the values that attracted young nurses to OR nursing.

PMID- 9287744
TI  - A nurse executive's nightmare. The rogue nurse.
AB  - An overview of rogue behavior by nurses is presented: drug diversion, posing as a
      nurse without a license sexual predator behavior and murdering patients. Several
      vignettes are given. Suggestions on how to recognize these behaviors and prevent
      these situations from happening follow.

PMID- 9287742
TI  - Bridging the care continuum for open heart surgery patients.
AB  - A pilot program followed patients who were recovering from coronary artery bypass
      graft procedures. A cardiac surgery nurse visits patients in their homes to
      provide physical assessments, reinforce discharge teaching and answer questions.
      Because of the pilot's success, the program was integrated with the transitional
      open heart unit.

PMID- 9287745
TI  - Substance abuse in nursing. Forming policies.
AB  - A written policy addressing impaired practice increases the likelihood that all
      nurses will be treated similarly. It also protects the organization legally. One
      large Midwestern medical center's approach to policy development, completed after
      1 year of task force work, is described.

PMID- 9287746
TI  - Does certification mean better performance?
AB  - This research addresses the efficacy of certification in nursing in terms of
      differences in job performance and self-esteem. Study results could help nurse
      managers determine hiring criteria, design professional development programs and
      restructure pay scales and reward systems.

PMID- 9287748
TI  - Managed care pure and simple.

PMID- 9287747
TI  - Implementing a nursing computerization project.

PMID- 9287749
TI  - Assessment of the need for nursing care.

PMID- 9287750
TI  - Managed care trends: the effect on subacute care.
AB  - Despite the recent mega-mergers of managed care organizations, health maintenance
      organizations (HMOs) are increasing. To understand what this growth means for
      subacute providers, trends in HMO enrollment must be identified.

PMID- 9287751
TI  - Managed care liability update.
AB  - As the volume of litigation involving managed care grows, the liability issues
      become clearer. For example, recent decisions demonstrate that failure to provide
      access to qualified physicians, failure to process claims appropriately, denial
      of claims and undue delay of treatment can and do lead to liability. Moreover,
      the federal Employment Retirement Income Security Act of 1974 (ERISA) won't
      protect the managed care providers, and physicians may sue the managed care
      organization if its policies or agents open them to liability.

PMID- 9287752
TI  - Take advantage of managed care opportunities.
AB  - Looking at the positive outcomes of managed care emphasizes the opportunities
      specific to nursing: continuum of care, critical pathways and patient education.
      With advanced information systems and managed care, nurses can demonstrate how
      models of preventive care, patient education and self-care should be set up and
      managed.

PMID- 9287753
TI  - The Carondelet experience.
AB  - Carondelet's preliminary data on their Community Nursing Organization indicate
      that members are satisfied; hospitalizations, length of stay and home health
      visits are down; client participation in health screening and health education
      activities is up; health problems and concerns are resolved and early
      intervention is effective.

PMID- 9287754
TI  - The Carondelet model.

PMID- 9287755
TI  - The University of Rochester experience.
AB  - To establish a school-based health center, it is more important than ever to plan
      for financial support for building a practice. It is difficult to get to and stay
      at the target enrollment for this population since it is ever-changing group of
      students. Plan for increased numbers of initial assessments since every year at
      least one-fourth of the enrollees in the program change. Work closely with
      primary care providers and make it clear in verbal and written communication that
      there is no intent to disrupt the relationship with the student. Assess risk of
      the population and attempt to predict utilization of services (number and type of
      encounters) and determine costs of care. It is also important to find ways to
      track hospitalizations, emergency room visits and other unscheduled access to
      care. Since adolescents frequently seek confidential care, parents and providers
      may be uninformed regarding the actual cost of management of covered lives in a
      managed care environment.

PMID- 9287756
TI  - The Carle Clinic.
AB  - Confronting the challenge of effective, efficient health care for the elderly has
      led to many variations in service delivery modalities. The approach employed by
      the Community Nursing Organization (CNO) is based on nurse coordinated care.
      Nurses are integrally involved in the authorization, coordination, evaluation and
      payment of services. The nursing role encompasses case management, including
      coordination of non-CNO covered services as well as those provided through the
      capitated payment schedule. Thus, in addition to authorizing CNO services, the
      nurse also may coordinate services such as physician visits, home repair,
      transportation, respite services and home-delivered meals, even though they are
      not covered financially under the auspices of the CNO. Preliminary findings
      indicate that this model may be successful clinically and financially by
      determining and utilizing an appropriate mix, intensity and duration of services.

PMID- 9287758
TI  - The Vanderbilt University experience.
AB  - The four models that form the University Community Health Services (UCHS) group
      practice include (1) Primary Care Centers, (2) Physician Partnerships, (3)
      Outsourcing of Nurse Practitioners, and (4) Employee-Based Health Care. Success
      is demonstrated by the following: UCHS practitioners deliver quality health care
      at 23% below the average cost of all other primary care providers, UCHS hospital
      inpatient rate is 21% below the average of all other primary care providers; the
      UCHS lab utilization rate is 24% below the other primary care providers;
      prescription drug utilization is 42% below average; and the latest patient
      satisfaction survey suggests that 82% of all patients (respondents) are very
      satisfied with their quality of care and on a scale of 1 to 4 (4 being the best)
      UCHS patients averaged services at 3.56. All the data suggest that UCHS providers
      have demonstrated above-average performance in cost-efficiency while delivering
      top quality health care.

PMID- 9287757
TI  - Community nursing centers--issues for managed care.
AB  - Community nursing centers (CNCs) can contribute significantly to the
      effectiveness and efficiency of managed care networks. The Silver Spring CNC is
      one example of a community nursing center that has demonstrated the ability to
      positively affect both the process and outcome of care for users from an urban
      community in Milwaukee. The CNCs must develop mechanisms to document both the
      process and outcomes of nursing practice and place these data squarely in the
      public policy arena if the full potential of these innovative practice
      organizations is to be realized.

PMID- 9287759
TI  - Merger motorway. Giving staff the tools to reengineer.
AB  - Mergers and health care agencies' response to mergers dominate current
      conversations in this evolving managed care environment. Hospitals are rapidly
      learning to adjust to declining occupancy rates and deceased utilization of
      resources. A business model to guide mergers was adapted to assist staff with the
      people, structural, cultural and political issues of organizational change.
      Creating successful new work environments, moving from a "We-they" mentality to
      unity and decreasing use of resources are outcomes described in this article.

PMID- 9287760
TI  - Flexible monitoring. Bringing technology to the patient.
AB  - Flexible monitoring helped to establish an intermediate care unit, close an
      intensive care unit (ICU) and reduce cost by decreasing length of stay (LOS) and
      matching patients to appropriate care. These efforts saved the hospital
      $3,260,215 over the first year while maintaining positive patient outcomes.

PMID- 9287761
TI  - Code team hazards.
AB  - Hospitalised resuscitation code) team members face unique risks: physical,
      chemical, environmental, psychosocial/ psychosocial and/or infectious hazards.
      The everyday health and safety dangers code teams encounter are discussed.

PMID- 9287762
TI  - Culture and consent.
AB  - Consent for surgical procedures is a surgeon's nontransferable legal duty.
      However, nurses often are involved in the communication of relevant, culturally
      sensitive information.

PMID- 9287763
TI  - Using service robots to deliver medications.

PMID- 9287764
TI  - Teaching staff about managed care.

PMID- 9287765
TI  - Patient information systems: unbiased information is key.
AB  - Successful patient information systems must have user-friendly services to
      transfer vast amounts of information. Whether it is preprinted discharge
      instructions for standard wound care, an algorithm-based triage discussion of
      one's chest pain, or simply a database to search out the current recommendations
      for flu shots or pediatric immunizations, the challenge for patient education in
      the communications revolution is high stakes indeed.

PMID- 9287766
TI  - HMOs must submit Medicare HEDIS.
AB  - Health maintenance organizations (HMOs) are now required to submit the Health
      Plan Employer Data and Information Set (HEDIS) for Medicare members to the
      federal government. The information will be used to assess an HMO's stability and
      performance in meeting its contractual obligations, including providing Medicare
      members with timely access to quality care. It also may be used to develop
      explanatory materials for Medicare beneficiaries trying to decide which health
      plan to join.

PMID- 9287767
TI  - Competency fairs: the answer to the staff-development dilemma.

PMID- 9287769
TI  - Looking for outcomes in all the wrong places...

PMID- 9287770
TI  - "Conscious sedation". Questions about the anesthesia continuum.
AB  - In this column, the Joint Commission on Accreditation of Healthcare Organizations
      (JCAHO) addresses the issue of conscious sedation, which standards apply and what
      JCAHO expects in regard to the development, implementation and evaluation of
      hospital-developed protocols for the care of sedated/anesthetized patients.

PMID- 9287768
TI  - The Social Security safety net.
AB  - Is it possible to build a stronger future for Social Security while, at the same
      time, protect the well being of the vulnerable elderly and maintain critical
      protection for families? Contrary to those who call for radical measures, the
      evidence is mounting: Social Security can be made stronger for the long-term with
      a package of modest, responsible reforms.

PMID- 9287771
TI  - Organizational diagnosis: a six-box model.
AB  - Six categories are used to perform an organizational diagnosis: purposes,
      structure, relationships, rewards, leadership and helpful mechanisms. A subacute
      care organization's diagnosis can determine the appropriateness and profitability
      of its current business, any gaps that must be rectified and the action plan that
      must be undertaken.

PMID- 9287772
TI  - Medicare marketing guidelines for managed care.
AB  - Health maintenance organizations must have their marketing materials approved by
      the federal government before disseminating them to Medicare beneficiaries. Draft
      national marketing guidelines have been issued to help ensure that the materials
      are understandable, contain the information Medicare beneficiaries need to make
      informed choices and facilitate comparisons of health plans. The guidelines also
      are intended to streamline the approval process.

PMID- 9287773
TI  - Including nursing in medical outcomes research.
AB  - Standardization efforts are going a long way to improve the quality of medical
      outcomes research, yet is nursing represented? Nursing's contributions to patient
      outcomes must be assessed properly and included in medical outcomes research.

PMID- 9287774
TI  - Legal update-1996, Part 1.
AB  - In the midst of managed care and hospital restructuring, delegating tasks
      previously performed by the nurse remains a constant issue. This month's column
      begins a summary of legal updates and discusses recent case examples and emerging
      trends.

PMID- 9287775
TI  - A standardized weight-based heparin protocol. Improving clinical outcomes.
AB  - A 3-year study evaluated various heparin dosing regimens. The clinical outcomes
      of a traditional non-weight-based method were compared with a newly designed
      standard protocol that related the heparin dose to patient weight. The relative
      time to achieve therapeutic anticoagulation, the number of additional intravenous
      heparin injections required and the length of hospitalization were all evaluated.
      Overall, it was found that the individualized weight-based protocol improved
      clinical outcomes and lowered medical costs.

PMID- 9287776
TI  - Tools for a successful interview.
AB  - Using a group interview tool encourages objective data. Guidelines make certain
      that the legal process is being followed. Tools for a successful interview
      process are provided.

PMID- 9287777
TI  - Reengineering in behavioral medicine.
AB  - Shifting demographics, local market issues and new strategic priorities
      precipitated an examination of operations at a large midwestern hospital. In this
      context, the Department of Behavioral Medicine embarked upon an intensive,
      structured process to reengineer its therapeutic model and operating systems. The
      principal objective of the redesign effort was a shift in the department's
      orientation from an intrapsychic inpatient paradigm to one that was short-term,
      crisis intervention-focused and fully integrated with community resources.

PMID- 9287778
TI  - Revising nursing documentation to meet patient outcomes.
AB  - Often, complex documentation forms place unnecessary burdens on nurses. A change
      in one hospital's patient care forms contributes to positive outcomes. With the
      revised documentation, nurses spend more time caring for patients while still
      meeting the Joint Commission on Accreditation of Healthcare Organizations'
      requirements.

PMID- 9287779
TI  - Accreditation surveys. Coping with the worst-case scenario.
AB  - Survey scheduled? Feeling out of control? An administrator from a small Texas
      hospital shares her worst-case experience-five surveys in 3 months.

PMID- 9287780
TI  - Self-scheduling in five med/surg units. A comparison.
AB  - As part of an Enhanced Professional Practice Model, self-scheduling was
      implemented in five medical/ surgical units. Each unit had varying degrees of
      success. The five factors that influenced successful implementation-committee
      structure, staff education, negotiation skills, guidelines and managerial support
      are discussed.

PMID- 9287781
TI  - Speak to me! An overview of patient communication systems.
AB  - One way to match professional expertise to the insatiable demand for patient
      information is to use new communication technologies. Patient communication
      systems and the opportunities they offer are explored. When using these emerging
      technologies, risks also should be addressed: not only must the information be
      accurate, but the systems must be secure.

PMID- 9287782
TI  - Heart failure in a health care organization.

PMID- 9287783
TI  - The three S's: salary, schedules and satisfaction.

PMID- 9287784
TI  - Arbitration without representation.

PMID- 9287785
TI  - Lean, mean and stupid!

PMID- 9287786
TI  - Technology vendors: how to get what you really want.
AB  - Influencing vendors to satisfy the institution's needs is paramount to success.
      When defining your system's vision, work with the vendor; share the larger
      picture. Guidelines to influence a vendor or consultant are provided.

PMID- 9287789
TI  - Report cards can improve choice.
AB  - Consumers want accurate and impartial information to help them select the best
      health plan. To arm them with such information, employers, state agencies and the
      media are publishing report cards for managed care plans. Disagreement exists,
      however, about the content and format of the report cards, as well as the best
      way to disseminate the information.

PMID- 9287788
TI  - Direct contracting: a new wave for subacute care.
AB  - Direct contracting, called "the wave of the future," poses particular challenges
      in two key areas for subacute care providers: quality of care and price. Using
      this process, employer groups bypass managed care organizations and directly
      contract with health care providers.

PMID- 9287787
TI  - Legal aspects of physician-assisted suicide.
AB  - Arguments presented before the Supreme Court reflect the national debate: Do
      mentally competent, terminally ill patients have a constitutionally protected
      right to seek a physician's aid to end their lives? Cases involving physician
      assisted suicide are discussed.

PMID- 9287790
TI  - Nursing care plans: are they required?

PMID- 9287791
TI  - Variable budgeting for staffing. Analysis and evaluation.
AB  - A successful resource-management system must be based on variable budgeting
      principles to account for fluctuation in patient census, methodically prepared
      through historical analysis of operations, carefully executed and monitored by
      accountable multidisciplinary managers. Significant attention must be paid to
      communication, positioning and stability of the patient care organization.

PMID- 9287792
TI  - Remote monitoring. Expanding a successful system.
AB  - A successful telemetry placement system moves into five medical/surgical areas
      and two step-down units. The updated equipment included an alarm gateway with an
      arrhythmia detection system. Telemetry signals are transmitted to a pager worn by
      nurses; remote display monitors allow nurses to eyeball arrhythmias and reset
      their alarm without going to a central station.

PMID- 9287793
TI  - Sounds of silence.
AB  - Strategies are described for dealing with three categories of reportable
      occurrences: inappropriate peer behavior, including substance abuse and
      behavioral problems; abuse, neglect and exploitation of patients; and issues
      concerning treatment orders. The American Nurses Association's (ANA) Code for
      Nurses, individual State Departments of Nursing License Regulations and State
      Intervention Projects for Nurses provide some direction for identifying,
      reporting and resolving occurrences.

PMID- 9287795
TI  - Measuring competencies of temporary staff.
AB  - Strategic staffing requires an understanding of a new model, what Charles Handy
      has named the "Shamrock Organizational Model," in which you have three equally
      valuable groups of staff a minimal core of full-time staff; a short-term
      contingency workforce; and a supplemental workforce for long-range temporary
      staffing needs. Ensuring the competency of all three is a nontransferable,
      although shared, responsibility of both the hospital and the supplemental
      staffing company.

PMID- 9287797
TI  - ORYX. The next evolution in accreditation. Joint Commission on Accreditation of
      Healthcare Organizations.
AB  - The Joint Commission on Accreditation of Healthcare Organization announces the
      details of an initiative to integrate performance measurement data into the
      accreditation process. As part of ORYX: The Next Evolution in Accreditation,
      accredited health care organizations will be required for the first time to
      collect data about the results of patient care.

PMID- 9287796
TI  - Job sharing at the managerial level.
AB  - Job sharing restructures a full-time position-two individuals share the
      responsibilities and the benefits of the position. If nurses are committed to
      making it work, this arrangement can succeed at the managerial level.

PMID- 9287798
TI  - Meeting JCAHO patient-education standards.
AB  - Specific standards and interdisciplinary coordination improve educational
      services and help to meet the Joint Commission on Accreditation of Healthcare
      Organization's standards. A flow chart detailing the patient/family education
      process is provided.

PMID- 9287794
TI  - Improving ambulatory surgery reimbursement.
AB  - As outpatient services become the new focal point for managed care, ambulatory
      surgery reimbursement structures are coming under increasing scrutiny. Operating
      room managers play a key role in developing ambulatory surgery payment mechanisms
      that are competitive, clinically meaningful and profitable. Operating room
      managers must understand the market forces that are redefining outpatient surgery
      reimbursement as well as the reimbursement mechanisms involved. Payment
      methodologies in ambulatory surgery are explored.

PMID- 9287799
TI  - Turnover among nursing home staff. A review.
AB  - Turnover is especially critical in nursing homes: continuity of care and personal
      relationships between care-givers and residents are important determinants of
      quality of care. Additionally, for the cognitively impaired nursing home
      resident, constant change of staff is bound to aggravate disorientation. Research
      demonstrates links between turnover and employment/employee characteristics and
      employment availability.

PMID- 9287801
TI  - Building a successful team through collaboration.
AB  - This is a tale of successfully building an interdisciplinary team in a stressful
      and rapidly changing ambulatory environment. It uses a framework where the leader
      does not have direct control over the assets but tries to influence the group to
      build trust, improve communication and collaborate toward common goals.

PMID- 9287800
TI  - Maximizing resources. 4 microanalysis assessment tool.
AB  - As the consequences of managed care create unstable financial trends and increase
      competition for health care organizations, it is essential to improve services.
      The microanalysis assessment tool provides a systematic process that examines
      resource utilization and helps to develop strategies to improve efficiency and
      reduce costs.

PMID- 9287802
TI  - Vital signs: are we monitoring the right parameters?
AB  - Measuring vital signs began with simple observations by the great masters. New
      technologies are now used to correlate old theorems about cardiovascular
      efficiencies into accepted measured parameters. Measuring temperature, blood
      pressure and respiration has never been easier.

PMID- 9287803
TI  - Staffing for census fluctuations.

PMID- 9287804
TI  - A tool for improving supplemental staffing.

PMID- 9287805
TI  - Improving recruitment and retention.

PMID- 9287806
TI  - Expanding a career progression program.

PMID- 9287807
TI  - Nursing bureau: a vision of self-governance.

PMID- 9287809
TI  - Wound care: the healing process.
AB  - When caring for a patient with a wound, regardless of its aetiology, a thorough
      assessment of the patient, the wound and any other relevant factors must be
      undertaken before care can be planned, if a successful outcome is to be achieved
      and realistic time scales set. Accurate wound assessment and appropriate care
      planning is dependant upon an understanding of the physiology of healing and any
      factors that may potentially delay or prolong the healing process. To be accurate
      and meaningful the information recorded should be concise, objective and
      comprehensive.

PMID- 9287810
TI  - Step into the future ... the language of change.

PMID- 9287808
TI  - Revitalizing nurses' week celebration.

PMID- 9287811
TI  - Boosting your career with a mentor.
AB  - Mentoring is the last topic in a series of six articles designed to help
      orthopaedic nurses adjust career goals and strengthen their professional and
      personal achievements. Becoming a protege to an experienced and successful person
      can be the linchpin that helps bring together the other elements-resume writing,
      job interviews, critical thinking, networking, and going back to school-you need
      to achieve your full potential. This article describes what to look for and
      expect from a mentor, how-to be a good protege, and the mentor-protege
      relationship. The author uses her personal experience as a mentor and protege to
      describe the risks and rewards of this influential relationship.

PMID- 9287812
TI  - The sling. Shoulder immobilization devices.
AB  - Currently a myriad of devices are available for immobilization of the injured or
      postsurgical upper extremity. Some of these devices are straightforward and
      easily used, but some are more complicated and require more familiarity for their
      successful application. However, even simple devices have the potential for
      misapplication and thus prevent their benefit to the patient. This article is the
      first in a 3-part series. The goals of the series are (1) to present and review
      several devices on the market used by shoulder surgeons to immobilize the upper
      extremity, and (2) to discuss proper application and precautions of their use. It
      is intended that this series will benefit nurses, therapists, and trainers
      involved in the use of these devices.

PMID- 9287815
TI  - Implementation of a pain management program in a community hospital.
AB  - Literature reports and staff concerns about management of patients' pain prompted
      nurses in a 337-bed suburban community hospital to implement a pain management
      education program. The Task Force tackled physician collaboration, securing
      resources, revising documentation tools, and designing an educational workshop.
      Their efforts resulted in the purchase of audiovisual materials for staff and
      patient use, addition of information about patient-controlled analgesia (PCA)
      devices to the hospital closed-circuit patient education TV channel, distribution
      of the Agency for Health Care Policy and Research (AHCPR) guidelines to hospital
      staff, revision of documentation tools, and the implementation of a 4-hour pain
      management education workshop for all professional nurses. Quality monitoring
      after the workshop reflected an improvement in nursing documentation of pain
      management.

PMID- 9287817
TI  - Pipkin types of fracture/dislocation of the hip.

PMID- 9287816
TI  - Understanding bone banking.
AB  - Allograft bone tissue is frequently used in orthopaedic reconstructive surgery.
      At many major medical centers, this procedure is as routine as the implantation
      of manmade metallic prosthetics. The harvesting, preparation, and delivery of
      bone used for transplantation is a complex and intricate process coupled with
      varying practices among different bone banks. This article provides the reader
      with information on current standards and practices in bone banking and
      transplantation. This will help the perioperative orthopaedic nurse deliver safe
      patient care during procedures using cadaveric bone and tissue.

PMID- 9287818
TI  - Entrepreneurship: I am an orthopaedic nurse!
AB  - In this time of downsizing and rightsizing, orthopaedic nurses are looking for
      new ways to apply their knowledge and remain orthopaedic nurses. For the
      experienced orthopaedic nurse, entrepreneurship may be in your future as an
      alternative to employment in the traditional health care settings. This article
      provides the realities and personal qualities required of an entrepreneur through
      the personal experiences of an orthopaedic nurse entrepreneur.

PMID- 9287814
TI  - Improving pain management in an acute care setting. The Crawford Long Hospital of
      Emory University experience.
AB  - PURPOSE: To identify which of three pain intensity measurement scales is most
      appropriate for use with patients admitted to the inpatient units of the study
      hospital. The following questions were addressed: Is one of the scales easier for
      most patients? Is the choice of scales influenced by nursing unit, age,
      education, race, SES, diagnosis, or type of pain experienced? Do patients
      perceive that a rating scale helps them describe their pain more effectively?
      SAMPLE: 267 patients admitted over a 3-week period completed a four-page
      questionnaire and demographic form distributed on admission. The primary
      admitting diagnosis for 39.5% of the sample reflected acute pain, 40.3% chronic
      pain, and 20.2 no pain. METHODS: Three pain rating scales were presented: two
      visual analogues (one contained a 100 mm line; the other contained six faces
      depicting graduated levels of distress); and a cognitive number rating scale.
      Each scale used a 0 (no pain) to 10 (worst pain possible) rating format. Patients
      completed the questionnaire by rating the intensity of pain experienced using
      each of the three scales once over the next 24 hours. The last page contained
      questions related to which of the scales was easiest to use, whether the scale
      was helpful or needed further explanation, and work and education information.
      The demographic form was completed from information contained in the patient
      record. FINDINGS: The scale selected most frequently was the visual analogue
      containing faces (48.6%), followed by the number (35.3%) and line scales (16.1%).
      None of the demographic information was found to significantly influence choice
      of preferred scale. A majority (85.8%) indicated a rating scale as helpful; only
      13.6% indicated a need for further explanation. The means for pain intensity
      ranged from 5.09 to 5.75. The interval between pain ratings for the majority (>
      71%) was less than 2 hours. Patients tended to tell the nurse about their pain
      when the intensity exceeded the midpoint on the scales. A reliability coefficient
      for the three scales was computed at alpha = 0.88. CONCLUSION: The use of rating
      scales for pain assessment in adult inpatient units was viewed positively by
      patients. Recommendations for incorporating self-ratings of pain intensity are
      set forth. Involving both patients and providers in the process is essential to
      improving both our processes and the outcomes achieved.

PMID- 9287819
TI  - Everyday ethics.
AB  - While dramatic issues such as assisted suicide and genetic engineering raise
      unique ethical questions for health care professionals, they are not the typical
      ethical concerns that nurses face in their daily practice. The more usual ethical
      situation or "everyday ethics" occur during the regular interactions that nurses
      have with patients, their families, and other health care providers. Everyday
      ethics is central to nursing practice. Being attuned to this aspect of
      professional practice gives meaning and purpose to nursing care. Typical clinical
      examples provide the backdrop for the discussion of everyday ethics. Through
      increasing their knowledge of ethical theory and values, their sensitivity to
      ethical issues in daily practice, their ability to use critical thinking, and
      their communication skills, nurses will be better able to provide ethically
      appropriate care to their patients.

PMID- 9287820
TI  - Tuberculosis drugs.
AB  - Tuberculosis is an old disease, and for some time thought to be almost eliminated
      in industrial societies. With the advent of the AIDS epidemic, it has made a
      comeback and often in a form more virulent than was seen in the past. This
      article summarizes the drugs used to treat the disease and suggests ways nurses
      may help keep this once underestimated problem in control.

PMID- 9287822
TI  - [Legal acting competencies in nursing and its importance for nursing as a
      profession relating to the new health and nursing legislation].

PMID- 9287821
TI  - [Prevention of HIV infections after professional exposure].

PMID- 9287823
TI  - [Nursing--what is it? The role of women in nursing is a historical one and did
      not happen by chance. A scientific discussion of this topic by Anna Sommer,
      president of the Austrian Nursing Society].

PMID- 9287825
TI  - [We have always done it that way! Ritualized work in nursing and its effect on
      the climate of the department and on the patients].

PMID- 9287826
TI  - [Professionalism in nursing. Nursing rounds--a step towards the future?].

PMID- 9287824
TI  - [Orientation on the nursing process].

PMID- 9287827
TI  - [Getting to know each other.... the importance of body hygiene for the emotional
      development].

PMID- 9287828
TI  - An evaluation of a self-directed program for feeding certification.

PMID- 9287813
TI  - The spondyloarthropathies.
AB  - The spondyloarthropathies represent a heterogeneous group of arthropathies
      including ankylosing spondylitis, reactive arthritis with Reiter syndrome as one
      subtype, arthritis associated with inflammatory bowel disease, arthritis
      associated with psoriasis, and juvenile spondyloarthritis. These conditions are
      linked by several common features: inflammatory arthritis involving the back, a
      high prevalence of HLA-B27, frequent tendon/ligament insertion inflammation, and
      several common extra-articular manifestations (iritis, skin lesions). Although
      not uncommon, these types of arthritis are more difficult to recognize than other
      types of arthritis such as osteoarthritis and rheumatoid arthritis.

PMID- 9287829
TI  - Caring for the caregiver.

PMID- 9287830
TI  - Parish nursing.

PMID- 9287831
TI  - Nothing but the truth?

PMID- 9287832
TI  - Her father's death.

PMID- 9287833
TI  - Problems with food packaging: are we promoting mealtime dependence in the
      elderly?

PMID- 9287834
TI  - Home safe home.

PMID- 9287836
TI  - One day in the life of an author--episode two.

PMID- 9287835
TI  - Focus groups: determining issues surrounding physical restraint use.

PMID- 9287837
TI  - Continuity of care: were we providing continuity of care for our clients?

PMID- 9287838
TI  - Sexuality in late years.

PMID- 9287839
TI  - Dispelling myths regarding aging.

PMID- 9287840
TI  - [Continuing education within the hospital as a counseling mandate].

PMID- 9287841
TI  - [Quality specialist--a new professional field].

PMID- 9287842
TI  - ["It is the simple things that are hard to do". Exchange of information between
      professional groups and facilities].

PMID- 9287843
TI  - [Care of victims of torture].

PMID- 9287845
TI  - [Nursing with Physicians Without Borders].

PMID- 9287846
TI  - [Dietetic measures in constipation].

PMID- 9287847
TI  - [In need of care--who is helping?].

PMID- 9287844
TI  - [Use of scoring systems in health care].

PMID- 9287848
TI  - [The social work visit--more than a nursing transfer].

PMID- 9287849
TI  - [The quality of care in ambulatory surgery has to be assured].

PMID- 9287851
TI  - [Literature searches on a theme. III].

PMID- 9287850
TI  - [Eucalyptus oil dressings in urinary retention].

PMID- 9287852
TI  - [The aroma of the great wide world].

PMID- 9287853
TI  - [Nosocomial urinary tract infections].

PMID- 9287854
TI  - [We are strengthening nursing].

PMID- 9287856
TI  - Problems of human sexuality.

PMID- 9287855
TI  - A paper exercise?

PMID- 9287857
TI  - Nutritional responsibilities.

PMID- 9287858
TI  - The named nurse: patient and nurse expectations.
AB  - The named nurse concept was introduced to provide patients with one nurse
      responsible for their care during a hospital stay. Research into patient and
      nurse expectations of the role is needed if the named nurse concept is to be
      evaluated.

PMID- 9287859
TI  - Running an erectile dysfunction clinic.
AB  - Men experiencing erectile dysfunction may appreciate attending a clinic where
      staff deal specifically with this problem. Several treatments are available for
      impotence, including hormone replacement, penile injections and vacuum therapy.

PMID- 9287860
TI  - Alternatives to mercury thermometers.
AB  - Training is essential to ensure the effectiveness of most temperature measurement
      devices. There are a number of factors that need to be considered when choosing a
      temperature measurement device for a particular clinical setting. There are
      currently four main alternatives to the mercury thermometer.

PMID- 9287862
TI  - Wound cleansing.
AB  - It is not necessary or cost-effective to cleanse wounds every time a dressing is
      changed. This Update describes the rationale behind wound cleansing and the
      optimum techniques to encourage healing.

PMID- 9287861
TI  - Nutrition in patients undergoing radiotherapy.
AB  - The metabolic changes accompanying cancer can contribute to a negative energy
      balance and weight loss. Many people with cancer will require additional
      nutritional support. Radiotherapy to the gastro-intestinal tract can cause
      debilitating symptoms affecting the ability to maintain nutritional intake.

PMID- 9287863
TI  - Glaucoma.

PMID- 9287864
TI  - Patient education in TENS pain management.
AB  - Chronic pain affects around 11% of the population and pain management costs the
      NHS Pounds 270 million a year. Conclusions are mixed but many studies have found
      TENS to be effective in the management of chronic pain, especially if used
      correctly and for a sufficient duration. The nurse's role as patient educator can
      be a strong influence on the therapy's success.

PMID- 9287865
TI  - Pressure-relief seating.
AB  - Chair-bound patients are significantly at risk of developing pressure sores.
      Little comparative research has been undertaken on pressure-relief seating. An
      understanding of a patient's requirements for pressure-relief seating will help
      when selecting products from the huge range available.

PMID- 9287866
TI  - Managing stress.
AB  - Managing stress is about achieving a balance between its positive and negative
      aspects. The final part of this module explores some of the common stress factors
      in nursing and considers a strategy which will help you manage your own
      stressors.

PMID- 9287867
TI  - Chronic fatigue syndrome.

PMID- 9287868
TI  - Drug administration and professional accountability.

PMID- 9287869
TI  - Where are clinical ladders headed?
AB  - Now that restructuring projects are under way, revision of the delivery system
      has expanded to related areas. One system that is being reviewed is the clinical
      ladder. This article discusses the future directions of clinical ladders within a
      restructured healthcare system.

PMID- 9287870
TI  - Counselling new graduates to find jobs.
AB  - Current trends in health care system hiring practices make it clear that new
      graduates need to consider additional alternatives for a successful job search in
      this highly competitive environment. Nurse executives, recruiters, human resource
      directors and faculty can help new graduates to find jobs, even during this
      period of tight job market. Strategies that executives, recruiters and faculty
      can use are discussed in this article.

PMID- 9287871
TI  - Relax!

PMID- 9287872
TI  - Alcohol withdrawal? This protocol works.

PMID- 9287874
TI  - Patient teaching tips from the horse's mouth.

PMID- 9287873
TI  - Epidural pain control--your job, too.

PMID- 9287875
TI  - Preserving renal function.

PMID- 9287876
TI  - The great mammogram debate.

PMID- 9287877
TI  - Antipsychotics.

PMID- 9287878
TI  - Herbal therapy: more than just folklore.

PMID- 9287880
TI  - Alternatives to litigation.

PMID- 9287879
TI  - Herbal therapy: there are risks.

PMID- 9287881
TI  - A new option for trigeminal neuralgia.

PMID- 9287882
TI  - Life's song lingers.

PMID- 9287883
TI  - Pediatric cervical spine injury sustained in falls from low heights.
AB  - STUDY OBJECTIVE: To determine whether history and clinical examination findings
      can identify young children who have sustained cervical injury after falling
      short distances. METHODS: We conducted a retrospective review of the medical
      records of children younger than 6 years old with the diagnosis of cervical
      vertebral fracture or cervical spinal cord injury after a fall of less than 5
      feet. Data from medical records over an average time span of 11 years at four
      large children's hospitals were compiled. RESULTS: We identified eight children
      who sustained cervical spine injury after a fall of less than 5 feet. These
      children ranged in age from 9 to 68 months. Three had rotary subluxation of C1,
      and three had subluxation of C1-C2. One of the children in the latter group also
      had an odontoid fracture. Two children had a fracture of C2. All the children had
      limited range of motion of the neck or neck pain. CONCLUSION: All children in
      this study with the diagnosis of cervical spine injury had clinical evidence of
      that injury on history or physical examination. Clinicians treating asymptomatic
      young children who sustain short falls may not need to perform radiographic
      evaluation of the cervical spine.

PMID- 9287884
TI  - Infants with isolated skull fracture: what are their clinical characteristics,
      and do they require hospitalization?
AB  - STUDY OBJECTIVE: We sought to identify the historical factors and physical
      examination findings typical of infants who have sustained isolated skull
      fracture (ISF)--in the absence of associated intracranial injury--after head
      trauma. We also assessed the risk of clinical deterioration (and therefore the
      need for inpatient observation) in infants with ISF. METHODS: We conducted a
      retrospective analysis of all patients younger than 2 years admitted to a
      tertiary care pediatric hospital with a diagnosis of ISF over a 3-year period.
      RESULTS: During the study period, 101 infants with radiographically proven ISF
      were admitted to the hospital. Falls were the most common reported mechanism of
      injury (n = 90 [89%]). Many falls involved short distances: 18 patients (18%)
      fell less than 3 feet. Nonaccidental trauma was suspected in only 10 patients
      (10%). Seventy-two patients (71%; 95% confidence interval [CI], 61%, 79%) had at
      least one of the clinical signs considered potential indicators of serious head
      injury: initial loss of consciousness, seizures, vomiting, lethargy,
      irritability, depressed mental status, and focal neurologic findings. In 97
      patients (96%; 95% CI, 89%, 98%), local findings of head injury (palpable
      fracture, soft-tissue swelling, or signs of basilar skull fracture) were noted on
      physical examination. None of the patients (0%; 95% CI, 0%, 3%) demonstrated
      clinical decline during hospitalization. All were neurologically normal on
      discharge. CONCLUSION: A diagnosis of ISF should be considered even in infants
      with minor mechanisms of head injury who appear well. However, infants with ISF
      rarely present without local signs of head injury on physical examination. If no
      other specific clinical concerns necessitate hospital admission, infants with ISF
      who have reliable caretakers may be considered for discharge home.

PMID- 9287885
TI  - Bicycle-related injuries among preschool children.
AB  - STUDY OBJECTIVE: To describe the circumstances, severity, and outcome of bicycle
      related injuries among hospitalized children younger than 5 years and to compare
      injuries in young children (< 5 years) and older children (5 to 14 years).
      METHODS: We studied a case series of children (0 to 14 years) with bicycle
      related injuries requiring hospital admission reported to the National Pediatric
      Trauma Registry (NPTR) between January 1986 and June 1996. RESULTS: Bicycle
      related injuries were reported for 4,041 patients; 219 (5%) involved children
      younger than 5 years. Two young children and 124 older children (3%) wore bicycle
      helmets. Young children were less likely than older ones to be injured in the
      street (46% versus 81%, P < .001) and were more likely to be injured at home in
      the driveway or yard (39% versus 9%, P < .001). Interaction with a motor vehicle
      contributed to injuries in 31% of young children and 47% of older children (P <
      .001). Forty-five percent of young children and 56% of older children sustained
      head injuries (P < .002). The fractions of children in each age group with facial
      trauma, abdominal or thoracic injury, and fractures were similar. Pediatric
      Trauma Scores, Glasgow Coma Scale scores, operating room use rates, and median
      number of hospital days were similar for both age groups. Rehabilitation or
      extended care was required by 1% of young children and 2% of older children. Two
      deaths occurred among young children (1%); 2% of older children died. CONCLUSION:
      Of patients with bicycle-related injuries reported to the NPTR, a minority are
      young children, but they have injuries similar in severity and outcome to those
      of older children. Because young children sustain severe injuries, including head
      trauma, helmets are indicated for them, as well as for older children.

PMID- 9287886
TI  - Occupational injuries among adolescents in Dunedin, New Zealand, 1990-1993.
AB  - STUDY OBJECTIVE: In this study we describe occupational injuries among
      adolescents (ages 15 through 19 years) presenting at a hospital ED in Dunedin,
      New Zealand, 1990-1993. METHODS: We used a new database to identify work-related
      injuries, as well as type of injury, cause of injury, injury site, occupation,
      industry, age, and sex. RESULTS: During the 4 years of the study, 1,361 work
      related injuries were treated at the ED, for an injury rate of 13.8 per 200,000
      hours worked (100 full-time equivalents). Males had a rate of 20.6 injuries,
      females 5.8 injuries, per 200,000 hours. Compared with injury rates from other
      studies, rates were lower than, but reasonably comparable to, those rates
      estimated through more detailed surveys. Main injury sites included upper
      extremities (mostly hands), head (mostly eyes), and lower extremities. Laceration
      was the main type of injury, followed by sprain/strain and foreign body. External
      cause of injury was mainly cutting/piercing objects, followed by foreign body and
      being struck by or against an object. The rate was highest for the 16- and 17
      year-olds and decreased for 18- and 19-year-olds. The rates of injuries in the
      construction sector were the highest of all occupational groups, at 27 injuries
      per 200,000 hours, followed by transportation/ communication, manufacturing
      (including meat and fish processing), and business and repair services. Laborers
      were the highest occupational risk group, with 36 injuries per 200,000 hours,
      followed by machine operators, precision production workers, and service workers.
      CONCLUSION: These findings may be helpful in focusing prevention efforts in high
      incidence areas. This study demonstrates how a well-planned data-collection
      system can overcome some of the previously described difficulties of getting
      prevention-oriented information from EDs.

PMID- 9287887
TI  - EMS for children: recommendations for coordinating care for children with special
      health care needs. Emergency Medical Services for Children, National Task Force
      on Children With Special Health Care Needs.
AB  - STUDY OBJECTIVE: To address the need for coordinated care for children and their
      families during the acute care phase of their hospitalization. METHODS: A
      multidiscipline task force developed this concept paper through a consensus
      process. The process was coordinated by the Emergency Medical Services for
      Children Program (a program of the Health Resources and Services Administration
      and the National Highway Traffic Safety Administration). The task force included
      representatives from prehospital care, acute care, rehabilitation, primary care,
      and education, as well as consumers. This representation provided a broad
      perspective on the needs of children and their families in the transition from
      hospital care to home. CONCLUSION: One designated individual is essential during
      the acute care phase who can assist the family with gaining information and
      resources to ensure a successful transition to community services and resources.
      This article provides a framework for acute care facilities and providers to use
      in planning services and working with acutely ill and injured children. Several
      recommendations highlight the need for care coordination to be initiated early in
      the child's hospitalization. An overview of services and resources (both health
      and educational) that a child and family may need is also provided. Such services
      and resources include identifying a care coordinator, working with the family to
      identify a primary care provider before hospital discharge, and building bridges
      with community-based health and education services.

PMID- 9287888
TI  - Access to emergency care under TennCare: do patients understand the system?
AB  - STUDY OBJECTIVE: To determine patient understanding of how to properly gain
      access to urgent and emergency medical care under TennCare, a government-mandated
      managed health care initiative designed to replace Medicaid in Tennessee.
      METHODS: We prospectively surveyed a convenience sample of ED patients at
      university hospital ED with an annual census of 50,000 during two periods (summer
      1994 and summer 1995). In 1994, 250 TennCare patients were enrolled (part 1). In
      1995, 199 were enrolled (part 2). RESULTS: Patients from seven different TennCare
      managed care organizations (MCOs) were interviewed. Thirty-eight percent of part
      1 patients and 37% of part 2 patients did not have or did not know the names of
      their primary care physicians (PCPs). Fifty-eight percent of the part 1 patients
      who knew their PCPs' names had never visited them. This figure had decreased to
      25% by the time part 2 patients were surveyed. Seventy-three percent of part 1
      patients interviewed did not call their PCPs before coming to the ED. This figure
      had decreased to 48% by the time part 2 patients were interviewed. Thirty-two
      percent of part 1 patients were aware that they were supposed to contact the PCP
      before visiting the ED, whereas 94% of part 2 patients were aware of this
      requirement. Thirty-one percent of part 1 patients and 40% of part 2 patients who
      tried to contact their PCPs were unsuccessful, most often because of a delay on
      the part of PCPs in returning calls. Fifty-six percent of part 1 patients and 69%
      of part 2 patients did not know that they might be held responsible for the bill
      if an ED visit was not considered a true emergency and was not approved by the
      MCO. CONCLUSION: Improvements in communication of pertinent information must be
      implemented in managed care systems such as TennCare to better inform
      participants of the proper use of the system. MCOs will not reduce inappropriate
      use of the ED if patients are not aware of their responsibilities and do not know
      their PCPs or how to gain access to them. PCP responsiveness to patients must
      also be improved.

PMID- 9287889
TI  - Use of the ED as a regular source of care: associated factors beyond lack of
      health insurance.
AB  - STUDY OBJECTIVE: To determine the characteristics and health care experiences of
      patients who identify the ED as their usual source of care. METHODS: We conducted
      a cross-sectional survey in a Level I trauma center ED at an urban teaching
      hospital. Our population comprised 892 adults who presented to the ED over the
      course of 30 days. We asked participants about their regular source of health
      care, previous health care experiences, and perceptions of the use of the ED.
      RESULTS: Patients who reported the ED as their regular source of care were three
      times more likely to have used the ED more than once in the preceding year. Among
      the regular ED users, 68% desired a physician as their regular source of care,
      and 46% of these subjects said they had tried unsuccessfully to get one in the
      preceding year. Five variables were associated with self-report of the ED as the
      regular source of health care: annual income less than $30,000, having been
      refused care in an office or clinic in the past, perception that an ED visit
      costs less than an office visit, absence of chronic illness, and unwillingness to
      use the ED if a $25 copayment were in effect. CONCLUSION: Low income, perceived
      mistreatment by health care providers, and misperception about charges contribute
      to use of the ED as a regular site for health care. These factors suggest the
      difficulty of altering health care use patterns in this group.

PMID- 9287891
TI  - Safety evaluation and confidence intervals when the number of observed events is
      small or zero.
AB  - A common objective in many clinical studies is to determine the safety of a
      diagnostic test or therapeutic intervention. In these evaluations, serious
      adverse effects are either rare or not encountered. In this setting, the
      estimation of the confidence interval (CI) for the unknown proportion of adverse
      events has special importance. When no adverse events are encountered, commonly
      used approximate methods for calculating CIs cannot be applied, and such
      information is not commonly reported. Furthermore, when only a few adverse events
      are encountered, the approximate methods for calculation of CIs can be applied,
      but are neither appropriate nor accurate. In both situations, CIs should be
      computed with the use of the exact binomial distribution. We discuss the need for
      such estimation and provide correct methods and rules of thumb for quick
      computations of accurate approximations of the 95% and 99.9% CIs when the
      observed number of adverse events is zero.

PMID- 9287890
TI  - Managed care and emergency medicine: conflicts, federal law, and California
      legislation.
AB  - The traditional use of the American ED, one of unrestricted access by patients
      and payment for services by insurers, is being questioned in this era of health
      care reform. Both primary care physicians and managed care organizations have
      questioned the use of the ED by patients without obvious problems of an emergency
      nature. We attempt to address this issue from the emergency medicine and managed
      care perspectives.

PMID- 9287892
TI  - What is confidence? Part 1: The use and interpretation of confidence intervals.
AB  - Hypothesis testing and the P value it generates are overemphasized in statistical
      analyses published in medical journals. An alternative, the confidence interval
      (CI), offers significantly more information to readers interpreting results.
      There have been many authoritative calls for the report of CIs in place of P
      values, such as that of the International Committee of Medical Journal Editors,
      whose guidelines for statistical reporting give the following instructions: "When
      possible, quantify findings and present them with appropriate indicators of
      measurement error or uncertainty (such as confidence intervals)," and "Avoid sole
      reliance on statistical hypothesis testing, such as the use of P values, which
      fails to convey important quantitative information." In this article, part 1, we
      provide an overview of CIs for the clinician reading the medical literature. We
      describe the advantages of CIs and explain and illustrate their proper
      interpretation. In part 2, which follows this article, we provide added
      information important for clinical researchers, including a precise definition of
      CIs, a compact reference to methods for calculating CIs in common situations, and
      an explanation of the difference between CIs and probability intervals.

PMID- 9287893
TI  - What is confidence? Part 2: Detailed definition and determination of confidence
      intervals.
AB  - In many cases, CIs should be reported in place of P values. The lower limit of a
      95% CI is chosen such that the probability of obtaining the value observed in the
      trial or a greater value is .025 and the upper limit such that the probability of
      obtaining the value observed or a lesser value is also .025. CIs for data from
      most clinical trials may be calculated easily with the use of formulas given in
      this article. A 95% CI is not the same as a 95% probability interval. The 95% CI
      contains values statistically consistent with the data obtained, whereas a 95%
      probability interval has a 95% probability of containing the true value of
      interest.

PMID- 9287894
TI  - Emergency medicine in Jordan.
AB  - The kingdom of Jordan is well known in the Middle East for the high-quality
      health care it provides its citizens and other patients from throughout the
      region. The specialty of emergency medicine is developing in Jordan along unique
      lines, mainly as an outgrowth of family medicine.

PMID- 9287895
TI  - Acute abdominal pain and vomiting in a 10-year-old girl.

PMID- 9287896
TI  - What, another milestone? The first steps in the founding of a specialty.

PMID- 9287897
TI  - Human rabies--Kentucky and Montana, 1996.

PMID- 9287898
TI  - Syncope in a 2-year-old: ED presentation of primary pulmonary hypertension.
AB  - We describe the case of a previously well 2-year-old girl who was found to have
      primary pulmonary hypertension (PPH) after presenting to the ED with syncope.
      Although physical examination findings were normal, an ECG and chest radiograph
      showed signs of PPH. The patient's hospital course was significant for syncopal
      episodes and sudden death while she awaited a heart transplant. This case
      illustrates that suspected cardiac syncope in the young warrants a focused ED
      evaluation with attention to causes of a life-threatening nature.

PMID- 9287900
TI  - Sucrose as an aid to manual reduction of incarcerated rectal prolapse.
AB  - Incarcerated rectal prolapse is a potential surgical emergency. We report a case
      in which a simple but effective technique involving the desiccating effect of
      granulated sugar (sucrose) was used to aid the manual reduction of prolapsed but
      viable rectal tissue.

PMID- 9287899
TI  - Gastric rupture with tension pneumoperitoneum: a complication of difficult
      endotracheal intubation.
AB  - Gastric rupture is a rare complication of difficult airway management. In cases
      of vigorous mouth-to-mouth ventilation, bag-valve-mask ventilation, or esophageal
      intubation, gastric rupture and massive intraperitoneal free air may cause
      tension pneumoperitoneum. Hemodynamic instability necessitates immediate
      intervention, including needle decompression of the peritoneum followed by
      surgical exploration. We recently encountered two cases of gastric rupture with
      tension pneumoperitoneum that occurred after difficult endotracheal intubation.
      This report describes the presentation, treatment, and prevention of this entity.

PMID- 9287901
TI  - Informed consent.

PMID- 9287902
TI  - Prehospital 12-lead ECG.

PMID- 9287903
TI  - Glucagon and phenol toxicity.

PMID- 9287904
TI  - Verapamil or diltiazem for acute rate control.

PMID- 9287906
TI  - Spirometric testing in acute asthma.

PMID- 9287907
TI  - Motor vehicle safety. American College of Emergency Physicians.

PMID- 9287908
TI  - Expanded roles of EMS personnel. American College of Emergency Physicians.

PMID- 9287905
TI  - Corticosteroids and asthma in children.

PMID- 9287909
TI  - Compensation arrangements for emergency physicians. American College of Emergency
      Physicians.

PMID- 9287910
TI  - Use of ultrasound imaging by emergency physicians. American College of Emergency
      Physicians.

PMID- 9287911
TI  - Appropriate interhospital patient transfer. American College of Emergency
      Physicians.

PMID- 9287912
TI  - Code of ethics for emergency physicians. American College of Emergency
      Physicians.

PMID- 9287913
TI  - The Cowlishaw symposium: introduction to the proceedings.

PMID- 9287914
TI  - Kenneth Fitzpatrick Russell: the first reader to the Gordon Craig Library.
AB  - A review of the life and achievements of Kenneth Fitzpatrick Russell, whose death
      in his 76th year robbed us of a civilized gentleman who was at the zenith of his
      creative output, would be a daunting task, if only because of the breadth of his
      hobbies and interests: art and medical literature; reading; sinology and seal
      carving; numismatics, medical philately; bookbinding, collecting bookplates;
      carpentry; metal work, including pewter casting and silversmithing; model ship
      building and cooking. Yet these various interests were simply a backdrop to his
      public career at the University of Melbourne and the Royal Australasian College
      of Surgeons, where he laid the foundations of an international reputation as
      scholar and collector.

PMID- 9287918
TI  - William Cheselden (1688-1752): humane anatomist and master surgeon.
AB  - William Cheselden (1688-1752) as a young man had a considerable reputation as an
      anatomist. He was one of the first to give a regular series of
      lecture/demonstrations and he incorporated this material into a basic text The
      Anatomy of the Humane Body, which was extremely popular and was in print for 100
      years. He was even better known as a surgeon, being on the staff of three
      teaching hospitals and recognized as the most skillful lithotomist of his time.
      His achievements are on record and he must be regarded as one of the greatest of
      British surgeons. Perhaps his greatest impact was his strong advocacy for the
      separation of surgeons from the Barber-Surgeons Company. He realised how much
      this long-established relationship was delaying the advancement of surgeons and
      surgery, and his vigorous action resulted in an Act of Parliament that severed
      the old ties and established in 1745 the Corporation of Surgeons, forerunner of
      the Royal College of Surgeons of England.

PMID- 9287915
TI  - Nom et lumiere: enlightenment through nomenclature (the 1996 Kenneth F. Russell
      Memorial Lecture).
AB  - The classification of living things is both an acknowledgement of biological
      relationships and an identification of their differences. When Linnaeus, in 1735,
      published Systema Naturae, he set in place a system of biological classification
      that saw its apogee in the invention of binomial nomenclature: the description of
      every living thing being embodied simply in two names, (i.e. a genus and the
      species within it). Linnaeus built on the work of scientific forebears, of whom
      Nehemiah Grew (1641-1712) was one of the most influential. Grew was a surgeon
      physician whose passionate interest was plant anatomy; his work led to the
      discovery and documentation of sexual dimorphism in plants. Grew's life and works
      are a witness to that philosophy which views nature as a continuum, a broad
      holistic entity in which discoveries in one biological field have ramifications
      in other areas. Grew allowed his scientific curiosity full rein, manifested the
      courage to publish his work and possessed the self-discipline to stand by the
      audit of his peers. Modern biological research and contemporary clinical practice
      owes much to the enlightenment engendered by the classification and nomenclature
      that developed from his work.

PMID- 9287916
TI  - Beneficence, temperance and medical science.
AB  - John Coakley Lettsom (1744-1815) founded the Medical Society of London and played
      a key role in the development of the Royal Humane Society. His Quaker background
      underpinned his interest in social reform. He established dispensaries and soup
      kitchens for the poor, recognized the need for public health measures in the
      control of disease, and advocated prison reform and education of the poor.

PMID- 9287917
TI  - Pott, pedantry and precision.
AB  - The historical section of the Gordon Craig Library at the Royal Australasian
      College of Surgeons contains a copy of Pott's major work, which includes most of
      his surgical papers. It also contains three volumes by Sir James Earle, which
      include most of Pott's papers, together with an account of the life of Pott. What
      follows is the basis of an illustrated lecture that sought to sample and review
      these books for those who do not have an opportunity to read them.

PMID- 9287919
TI  - Abernethy and the golden age of surgical teaching.
AB  - A beautifully bound handwritten volume, John Abernethy's Lectures on Surgery in
      the Cowlishaw Collection at the library of the Royal Australasian College of
      Surgeons proved the stimulus for a study of the work of Abernethy and two of his
      contemporaries in 19th century London, namely Charles Bell and James Paget. All
      excelled in the teaching of anatomy, physiology and pathology, continuing the
      Hunterian tradition. Abernethy extended Hunter's work on ligation of aneurysms
      and was a prime mover in the establishment of the Medical School at St
      Bartholomew's; Bell likewise assisted in the foundation of the Middlesex Hospital
      Medical School and made important discoveries relating to the nervous system and
      the circulation; James Paget excelled in the description of surgical pathology as
      a basis for disease presentation. All three became Fellows of the Royal Society
      and left a legacy of eponymous structures and important pathological and clinical
      knowledge.

PMID- 9287920
TI  - A debt to Alexis: the Beaumont-St Martin story.
AB  - This paper is based on the book Experiments and Observations on the Gastric Juice
      and the Physiology of Digestion, originally published in 1833. The book held in
      the Cowlishaw Collection of the Royal Australasian College of Surgeons is the
      Edinburgh edition of 1838, which contains a preface by Andrew Combe, MD. The
      paper explores several aspects of the Beaumont-St Martin story, from St Martin's
      original injury and the primary care undertaken by Dr William Beaumont, whose
      numerous studies of the actions and reactions of the stomach were made possible
      because St Martin was left with a permanent gastric fistula. While the debt we
      owe to Beaumont is often acknowledged, patients are not mere machines and
      surgeons must recognize that surgery also owes a debt to its patients; in this
      case, to Alexis St Martin for what he permitted by way of experiment.

PMID- 9287921
TI  - Pare as a neurosurgeon.
AB  - The Cowlishaw Collection gives a splendid representation of the works of a
      Ambroise Pare (1510-1590). His Complete Works, in the great French edition edited
      by J.F. Malgaigne, are essential in any study of Pare's achievement, but the 1649
      English edition provides a good basis for consideration of Pare's practice in
      what would now be termed neurosurgery. Pare had a large clinical experience in
      head injury management. His patients included Henri II King of France, who died
      from a penetrating orbital wound, and be described a number of other craniofacial
      wounds sustained in war or in warlike sports. His surgical instruments and
      operative techniques do not appear very innovative, but were doubtless good in
      their day; his methods of trephination compare favourably with those of the
      English surgeon John Woodall, his younger contemporary. He operated on head
      injuries and cranial infection, but had no capacity to treat intradural
      conditions, such as cerebral abscesses and tumours: his technical limitations are
      obvious, and the physicians on whom he had to rely could give him no guidance in
      neurological diagnosis. He was keenly interested in developmental malformations,
      and described several conditions that would now be referred to a paediatric
      neurosurgeon. Pare is of great historical importance as an outstanding
      Renaissance surgeon, whose influence extended throughout the literate world, and
      as far as Japan. With him, France replaced Italy and Spain in leadership in
      European surgical progress, a position that France retained at least until the
      age of Hunter.

PMID- 9287922
TI  - Home away from home.
AB  - A discourse on the careers and events that relate to Everard Home's Lectures on
      Comparative Anatomy, published in six volumes, of which the final supplementary
      volume of 1828 is in the Gordon Craig Library. This volume contains 68
      engravings, of subjects as diverse as the stomach of the alpaca and the female
      organs of the duckbilled platypus Ornithorhynchus, and Home's credentials occupy
      about half of the title page.

PMID- 9287923
TI  - Electrohydraulic lithotripsy: an effective and economical modality of endoscopic
      ureteric lithotripsy.
AB  - BACKGROUND: Electrohydraulic lithotripsy (EHL) has been available for endoscopic
      treatment of urinary calculi since 1960, but the large probe size and concerns
      regarding safety had previously restricted its use to the treatment of bladder
      calculi. However, recent refinements have made it particularly suitable for the
      treatment of ureteric calculi. METHODS: The authors report their initial
      experience using EHL in conjunction with mini-ureteroscopy in the treatment of 94
      ureteric calculi in 89 patients. The size of the calculi ranged from 3 to 19 mm
      in diameter, with a mean of 8.2 mm. The mean operating time was 29 min, ranging
      from 10 to 120 min. RESULTS: A complete fragmentation rate of 91.5% of the
      calculi was achieved. There were no major complications and a low incidence of
      minor complications: haematuria (2.2%), urinary tract infection (3.4%) and
      postoperative ureteric colic (2.2%). There were four cases of minor ureteric
      perforations (4.5%); all were successfully treated using conservative measures.
      CONCLUSIONS: It is concluded that EHL is a safe and effective method of treating
      ureteric calculi.

PMID- 9287924
TI  - A prospective randomized controlled trial comparing suprapubic with urethral
      catheterization in rectal surgery.
AB  - BACKGROUND: Bladder drainage is necessary for several days following rectal
      surgery. Urethral catheterization has long been known to be associated with
      significant morbidity. Therefore a prospective randomized trial was performed to
      determine if this morbidity could be decreased by suprapubic catheterization.
      METHODS: One hundred and thirty-seven patients undergoing rectal surgery were
      prospectively randomized to either suprapubic or urethral catheterization.
      RESULTS: After exclusions, 108 patients were analysed. Of the 49 patients with
      suprapubic catheters there was 14% morbidity, and of the 59 patients with
      urethral catheters there was 32% morbidity. Significant bacteriuria was halved
      with suprapubic catheterization. Patient acceptability of suprapubic
      catheterization was high, and there was no increased morbidity in any of the
      areas studied. CONCLUSIONS: This study suggests that suprapubic catheterization
      has advantages over urethral catheterization with decreased bacteriuria, and
      greater patient acceptability. However, the significance of decreased bacteriuria
      is not clear and therefore we can only say suprapubic catheter drainage is
      comparable to urethral catheter drainage.

PMID- 9287925
TI  - Colorectal surgery in the elderly: an audit of surgery in octogenarians.
AB  - BACKGROUND: Morbidity and mortality rates are higher in elderly compared to
      younger patients undergoing colorectal cancer surgery. This study was undertaken
      to see whether this finding applied to all colorectal surgery in the elderly and
      if so to try to identify the determining factors. METHODS: All patients
      undergoing colorectal surgery between 1975 and 1990 were entered into a
      computerized database. Patients were divided into two groups, those less than 80
      years (< 80) and those 80 years and more (80+), and compared with regard to the
      type of surgery performed, the patient's race, the seniority of the surgeon, the
      patient's disease, the operation performed and the postoperative morbidity and
      mortality. In addition, patients undergoing major resectional surgery and
      patients undergoing colorectal cancer surgery were compared separately. RESULTS:
      Of 2011 admissions, 88 were for patients of 80+. The male to female admission
      rate was 1:0.79 in the < 80 group and 1:1.25 in the 80+ group. More surgical
      procedures were performed by consultants in older patients. More emergency
      admissions were for 80+ patients. Rectal, sigmoid and right colonic pathology was
      more common in the elderly. Very few elderly patients were admitted with minor
      anorectal problems. Rectal prolapse and colorectal cancer were the commonest
      causes for admission in octogenarians. There were more pulmonary and
      cardiovascular postoperative complications in 80+ patients. Urinary tract
      infections were also more common. The postoperative mortality rate was higher in
      older patients (7.9 vs 1.4%). Four hundred and sixty-two patients underwent major
      resectional surgery and 45 were 80+. Surgery for diverticular disease was more
      frequent in younger patients (13.4 vs 2.2%) and cancer surgery in older patients
      (93.3 vs 70.5%). The postoperative mortality rate was higher in the elderly (11.1
      vs 3.6%). Three hundred and thirty-six major resections were for cancer and 42
      were 80+. Emergency surgery was performed more commonly in the older group (38.1
      vs 14.9%). The rate of advanced disease seemed to be similar in both groups. The
      postoperative death rate was higher in the elderly (11.9 vs 3.4%). CONCLUSIONS:
      Elderly patients were more likely to die from cardiopulmonary problems after
      surgical interventions than either from their primary disease or from the surgery
      undertaken for it. Good postoperative cardiopulmonary support should thus be
      provided for all such patients.

PMID- 9287926
TI  - Laparoscopic-assisted compared with open total colectomy in treating slow transit
      constipation.
AB  - BACKGROUND: Total colectomy is the procedure of choice when slow transit
      constipation (STC) can be confidently diagnosed. A laparoscopic-assisted
      technique (LTC) may be potentially advantageous over traditional open technique
      (OTC) in the treatment of this benign condition. METHODS: A historical control
      (non-randomized) study was performed on patients diagnosed to have STC after
      clinical, anorectal physiologic and transit marker studies. All earlier
      consecutive patients underwent OTC and the latter consecutive patients underwent
      LTC. The intra-operative time, blood loss, postoperative ileus recovery, duration
      of hospitalization and complications were recorded. A bowel function and patient
      satisfaction questionnaire was administered on follow-up. RESULTS: Twenty-four of
      411 patients were found to have STC; 17 (2 men, 15 women; mean age, 40 (standard
      error of mean [SEM] 5) years) underwent OTC and 7 (2 men, 5 women; mean age, 39.5
      (SEM 6) years) underwent LTC. There were significant improvements in the stool
      frequency, need for assisted evacuation and abdominal distension (P < 0.05) after
      both procedures; 96% were fully satisfied with the resulting bowel function.
      However, OTC patients were less satisfied with the cosmetic outcome (P < 0.05).
      Intra-operative time for LTC was longer by a mean 74 min (P < 0.05).
      Postoperative blood loss, recovery of ileus and hospitalization time were the
      same in both groups. There were no deaths. The complication rates were 43% for
      LTC and 24% for OTC. The predominant complication was bowel obstruction for which
      two patients (both OTC) required adhesiolysis. CONCLUSIONS: Both OTC and LTC
      improve bowel function for STC;LTC gives a better cosmetic result, but takes
      longer to perform.

PMID- 9287928
TI  - Ventilation tube duration versus site of placement.
AB  - BACKGROUND: The duration a ventilation tube remains in the tympanic membrane is
      thought to be related to the design of the ventilating tube, and to the site of
      placement of the ventilation tube into the tympanic membrane. Theoretically a
      ventilating tube placed superiorly should remain longer than one placed
      inferiorly. METHODS: A prospective study was designed to test the hypothesis that
      ventilation tubes placed into the antero-superior quadrant of the tympanic
      membrane remained longer than those placed into the antero-inferior quadrant.
      RESULTS: In 106 children no statistically significant difference in duration was
      identified using three designs of ventilation tube. CONCLUSIONS: Ventilating
      tubes placed antero-superiorly into the tympanic membrane do not have a longer
      duration than those placed antero-inferiorly.

PMID- 9287927
TI  - Postanal repair for faecal incontinence: long-term follow-up.
AB  - BACKGROUND: To determine the long-term outcome of postanal repair, and to assess
      whether the preoperative and physiological tests had any bearing on this outcome.
      Review included an opportunity for assessment with anal manometry and anal
      ultrasound. METHOD: Review of all patients (n = 22) over a 10 year period from
      1986 to 1996. Comparison was of pre-operative symptoms to symptoms at review.
      Correlation of outcome with pre-operative manometry and the results of manometry
      and ultrasound at review (n = 6) was determined. RESULTS: Assessment was possible
      in 19 of the 22 patients. Follow-up ranged from 2 to 10 years (median, 8 years).
      Two had stomas created at 6 and 9 months and are considered failures. Seven
      patients considered the operation a success, in four it improved their symptoms
      and in six it was considered a failure. Comparison of pre- and postoperative
      symptoms scores found a statistically significant improvement (P = 0.0093; two
      tailed Wilcoxon signed rank sum test). The outcome was not influenced by the
      results of pre-operative anal manometry. Anal ultrasound found five sphincter
      defects in six patients. Such defects did not preclude improvement from postanal
      repair. CONCLUSIONS: Although the results showed improvement or success in only
      11 (58%) of the patients this was felt to be important given that these patients
      may have few alternatives other than complicated procedures or a stoma. Postanal
      repair has a place in the management of faecal incontinence.

PMID- 9287929
TI  - Congenital bulbar urethral strictures occurring in three brothers: comment.

PMID- 9287930
TI  - Delayed rupture of the spleen 5 1/2 years after conservative management of
      traumatic splenic injury: comment.

PMID- 9287931
TI  - Biliary ascariasis: a worm in the bag.

PMID- 9287932
TI  - Angiosarcoma occurring with chronic osteomyelitis and residual foreign material:
      case report of a late World War II wound complication.
AB  - The case is reported of a World War II veteran who developed an angiosarcoma at
      the site of wounding 46 years previously. The wound was complicated by retained
      foreign material and chronic infection involving bone. The patient died, 6 weeks
      after tumour diagnosis, from a complication of the disease. There is slight but
      definite risk of tumour development in association with retained foreign
      material. This risk may be greater in older patients who have retained this
      foreign material for long periods and where the presence of the material is
      complicated by chronic infection.

PMID- 9287933
TI  - Anomalous azygos vein: a potential danger during endoscopic thoracic
      sympathectomy.
AB  - A report of a patient with an azygos lobe and an associated anomalous azygos vein
      covering the upper thoracic sympathetic chain. This anomaly poses a significant
      risk during the procedure of endoscopic thoracic sympathectomy. A chest X-ray is
      useful in detecting this anomaly and alerting the surgeon to potential problems.

PMID- 9287935
TI  - The abductor digiti minimi flap: a case report and review.
AB  - The use of an abductor digiti minimi flap is reported here for coverage of a
      dorso-ulnar defect of the hand following excision of a tumour. This flap has not
      been widely used before. The abductor digiti minimi flap appears to have minimal
      donor site morbidity and a reliable vascular supply, and is straightforward to
      raise. The authors consider it would be a useful flap to provide cover on the
      ulnar side of the hand and wrist in patients who do not require highly dextrous
      use of the little finger.

PMID- 9287934
TI  - Gastric cancer in the bypassed segment after operation for morbid obesity.
AB  - A case is reported in which two separate adenocarcinomas were detected in the
      bypassed distal stomach 13 years after gastric stapling with loop gastro
      enterostomy was performed for the treatment of morbid obesity. Retrograde
      endoscopy via the afferent loop was used to establish the diagnosis. Although
      gastritis and metaplasia have been described in the bypassed stomach, only one
      case of carcinoma in this area has previously been reported.

PMID- 9287936
TI  - Swimming-associated haemorrhagic colitis due to Escherichia coli O157:H7
      infection: evidence of prolonged contamination of a fresh water lake.
AB  - We describe an Escherichia coli O157:H7 outbreak associated with a fresh water
      lake at a county park. Campers were surveyed for diarrhoeal illness within 10
      days of their visit, and a case-control study of day visitors was conducted. A
      confirmed case was a symptomatic person with a stool culture positive for E. coli
      O157:H7 and a probable case was a person with bloody diarrhoea. Clinical isolates
      of E. coli O157 were subtyped by pulsed field gel electrophoresis (PFGE). In the
      camper survey, 12 (38%) of 32 swimmers had a diarrhoeal illness (relative risk
      [RR] = 12.4; 95% confidence interval [CI] = 1.7-89.7). For the case-control
      study, the 12 cases were more likely than controls to have purposefully ingested
      lake water (odds ratio [OR] = 6.9, 95% CI = 0.9-55.8). The PFGE patterns of six
      clinical isolates were indistinguishable. This report further demonstrates that
      contaminated fresh-water lakes can be the source of community outbreaks of E.
      coli O157:H7.

PMID- 9287941
TI  - The effect of ice-cream-scoop water on the hygiene of ice cream.
AB  - A survey of unopened ice cream, ice cream in use, and ice-cream-scoop water (n =
      91) was conducted to determine the effect of scoop water hygiene on the
      microbiological quality of ice cream. An aerobic plate count around 10(6) c.f.u.
      ml-1 was the modal value for scoop waters. Unopened ice creams generally had
      counts around 10(3)-10(4) c.f.u. ml-1 and this increased by one order of
      magnitude when in use. Many scoop waters had low coliform counts, but almost half
      contained > 100 c.f.u. ml-1. E. coli was isolated in 18% of ice creams in use,
      and in 10% of unopened ice creams. S. aureus was not detected in any sample.
      Statistical analysis showed strong associations between indicator organisms and
      increased counts in ice cream in use. EC guidelines for indicator organisms in
      ice cream were exceeded by up to 56% of samples.

PMID- 9287939
TI  - Minimum inhibitory concentration (MIC) of some antibiotics against Vibrio
      cholerae O139 isolates from Pondicherry.
AB  - The antibiotic susceptibility pattern of Vibrio cholerae O139, Bengal, an
      emerging intestinal pathogen has been determined by the Kirby Bauer technique and
      the MIC values of some antibiotics against these strains by agar dilution
      technique. All the strains were susceptible to tetracycline, norfloxacin,
      ciprofloxacin and a majority was susceptible to gentamicin (95.7%) and nalidixic
      acid (82.9%). Only 51% were susceptible to cefotaxime and most strains were
      resistant to furazolidone (95.7%), ampicillin (87.3%) and co-trimoxazole (91.5%).
      The study shows the importance of judicious use of antibiotics in cholera cases
      and the need for monitoring the susceptibility status of these strains
      particularly because of their ability to cause extra-intestinal infections like
      septicaemia.

PMID- 9287940
TI  - Helicobacter antibodies in 1973 and 1994 in the adult population of Vammala,
      Finland.
AB  - Changes in Helicobacter pylori seroprevalence were studied determining IgG and
      IgA antibodies of 408 randomly selected adults aged 15-74 years living in
      Vammala, Finland in 1973 and of 504 similarly selected subjects in 1994.
      Seroprevalence increased by age at both time points. The age-adjusted
      seroprevalence rate was clearly lower in 1994 than in 1973 (31 vs. 56%, P =
      0.001). Paired serum samples of 224 subjects collected in 1973 and 1994 showed
      that the antibody status remained unaltered in 92%; 4% seroconverted and 4%
      seroreverted within the 21 years. The decrease in the seroprevalence rate in the
      population and the persistence of individual antibody status over two decades
      support a difference in H. pylori infection rates among birth cohorts over time
      rather than continuous acquisition of new infections with advancing age. Thus the
      risk of helicobacter infection in Vammala, Finland has been highest in childhood
      and continuously decreased at least for the last five decades.

PMID- 9287937
TI  - Outbreaks of food poisoning in adults due to Escherichia coli O111 and
      campylobacter associated with coach trips to northern France.
AB  - Thirty-seven out of 48 people on a coach excursion to northern France developed
      gastrointestinal symptoms within 4 days of the trip. Twenty-six had stool samples
      positive for Escherichia coli O111, 8 were also positive for Campylobacter
      species, and 1 was positive for campylobacter alone. Strains of E. coli were
      positive for the effacing and attaching protein (eaeA) gene, but negative for
      other E. coli virulence genes, and therefore belonged to the enteropathogenic E.
      coli (EPEC) group. Twenty-two out of 37 people in a second party which followed
      the same itinerary 2 weeks later also became ill. One had a stool sample positive
      for E. coli O111. Analytical epidemiology suggested that the source of infections
      was a restaurant in northern France at which both parties had eaten.

PMID- 9287942
TI  - Serotyping of Streptococcus pyogenes isolated from common and severe invasive
      infections in Japan, 1990-5: implication of the T3 serotype strain-expansion in
      TSLS. The Working Group for Group A Streptococci in Japan.
AB  - To clarify the relationship between the epidemics of severe invasive group A
      streptococcal infections (streptococcal Toxic Shock-Like Syndrome: TSLS) and
      common group A streptococcal infections in Japan, we examined the T serotypes of
      S. pyogenes strains (group A streptococci) isolated from clinical specimens of
      the streptococcal infections (17999 cases) in the period 1990-5, including the
      severe infections (TSLS) (29 cases) in the period 1992-5. Characteristic points
      of the analyses were: (1) dominant serotypes of the infections in these periods
      were T12, T4, T1, T28 and TB3264, which were consistently isolated; (2) isolates
      of T3 rapidly increased through 1990 to 1994 while T6 decreased in the period
      1990-3; (3) when Japanese area was divided into three parts, T3 serotype tended
      to spread out from the north-eastern to the south-western area; (4) strains of T3
      and T1 serotypes were dominant in the TSLS. Dominant-serotype strains of
      streptococcal infections did not always induce severe infections and dominance of
      T3 serotype in the TSLS seemed to be correlated with the increase of T3 in
      streptococcal infections. These results may indicate that certain clones of S.
      pyogenes are involved in the pathogenesis of the TSLS.

PMID- 9287943
TI  - The influence of demographic change and cumulative risk of pelvic inflammatory
      disease on the incidence of ectopic pregnancy.
AB  - A retrospective study was carried out to determine the recent epidemiology of
      ectopic pregnancy in England between the biennial years 1988/9 and 1992/3. The
      number of ectopic pregnancy cases were combined with numbers of conceptions and
      the rates analysed for trend over time. The incidence of ectopic pregnancy rose
      significantly (P = 0.05) over this period. However, this could be entirely
      explained by increasing numbers of births in older women and a highly significant
      positive association was found between risk of ectopic pregnancy and maternal age
      (P < 0.0001). Over the study period the incidence of ectopic pregnancy in women
      aged 40 years or more was over 14 times that observed in those under 16 years of
      age. It is suggested that this reflects cumulative risk of acquiring pelvic
      inflammatory disease. The surveillance of ectopic pregnancy provides a useful
      indicator of the level of reproductive morbidity in women.

PMID- 9287944
TI  - Cryptosporidiosis in children during a massive waterborne outbreak in Milwaukee,
      Wisconsin: clinical, laboratory and epidemiologic findings.
AB  - During the spring of 1993 an estimated 403000 residents of the greater Milwaukee,
      Wisconsin area experienced gastrointestinal illness due to infection with the
      parasite Cryptosporidium parvum following contamination of the city's water
      supply. To define the clinical, laboratory and epidemiologic features of outbreak
      associated cryptosporidiosis in children, medical and laboratory records for all
      children submitting stool samples to the microbiology laboratory of the
      Children's Hospital of Wisconsin between 7 April and 13 May 1993 were reviewed
      retrospectively. Interviews with parents were also conducted to obtain additional
      clinical history. Cryptosporidium, as the sole pathogen, was identified in stools
      from 49 (23%) of the 209 children enrolled in the study. Children with laboratory
      confirmed cryptosporidiosis were more likely to live in areas of Milwaukee
      supplied with contaminated water (RR = 1.92, CI = 1.19-3.09), to be tested later
      in their illness (P < 0.05), to have submitted more than one stool specimen (P =
      0.01), to have an underlying disease that altered their immune status (RR = 2.78,
      CI = 1.60-4.84), and to be older than 1 year of age (RR = 2.02, CI = 1.13-3.60).
      Clinical illness in these patients was more prolonged and associated with weight
      loss and abdominal cramps compared with Cryptosporidium-negative children. In the
      context of this massive waterborne outbreak relatively few children had
      documented infection with Cryptosporidium. If many children who tested negative
      for the parasite were truly infected, as the epidemiologic data suggest, existing
      laboratory tests for Cryptosporidium were insensitive, particularly early in the
      course of illness.

PMID- 9287938
TI  - Salmonella isolated from humans, animals and other sources in Canada, 1983-92.
AB  - A total of 89760 human and 22551 non-human isolates of salmonella were serotyped
      in Canada during the period 1983-92. There were 2180 reported outbreaks
      associated with 10065 cases during the 10-year period. The most common salmonella
      serovars isolated from human and non-human sources were S. typhimurium and S.
      hadar. The third and fourth most common serovars from human sources were S.
      enteritidis and S. heidelberg, respectively, and from non-human sources they were
      S. heidelberg and S. infantis. The number of S. typhimurium isolations from human
      and non-human sources showed a downward trend over the 10-year period. A total of
      222 outbreaks of S. typhimurium associated with 1622 cases occurred. The S. hadar
      isolations from human and non-human sources reached a peak during the years 1987
      90 and declined thereafter. The number of human isolates of S. enteritidis
      increased until 1985 and fluctuated at a level of 8.3-12.8% of all human isolates
      thereafter. Seventy-three outbreaks of S. enteritidis infection associated with
      568 cases occurred. More than 50% of the S. enteritidis infections in humans were
      caused by phage type (PT) 8. During the review period, infections caused by PT4
      were less common and were almost exclusively found in people who had travelled
      abroad. The annual isolation rates of S. heidelberg from human and non-human
      sources increased steadily during the period. Bacteriophage typing of serovars
      from outbreaks showed that contaminated food products of poultry and bovine
      origin were common sources of human infection. Salmonella typhi was identified as
      the cause of 43 small outbreaks affecting 116 persons.

PMID- 9287946
TI  - Epidemiological features of entero non-poliovirus isolations in Belgium 1980-94.
AB  - Between 1980 and 1994 the virological laboratory of the Institute of Hygiene and
      Epidemiology was responsible for the typing of enteroviruses, isolated by other,
      mainly university, hospital laboratories. Altogether 3333 strains of entero non
      polio (EnP) were typed. The number and the most common types of EnP virus
      isolations varied from year to year. Each year two to three predominant types
      determined the main character of the EnP associated illness seen.

PMID- 9287947
TI  - Assessment of neutralizing antibodies elicited by a vaccine (Nakayama) strain of
      Japanese encephalitis virus in Taiwan.
AB  - A total of 368 blood specimens were resampled from a serum collection containing
      2914 blood samples which were collected by a random sampling in Taiwan in 1991.
      The plaque reduction neutralization test was applied to evaluate the neutralizing
      ability to two strains of Japanese encephalitis viruses, i.e. Nakayama (the
      present vaccine strain) and JE5 (a Taiwan isolate). The result revealed that
      antibodies against JE virus were present in each stratified age group. Antibody
      positive rates were both highest in the group older than 70 years although the
      lowest rates were located in different groups. In addition, the result showed
      that the immunogenicity potency of the antibody induced by the vaccine strain did
      not have a good coverage against JE5. The rate of neutralizing antibodies above
      the level of protective efficacy of the present vaccine was limited as low as
      37.93%. Efficacy of the vaccine used at present was apparently not efficient.
      Consideration of a more promising vaccine may be necessary.

PMID- 9287945
TI  - Clearance of young parasite forms following treatment of falciparum malaria in
      humans: comparison of three simple mathematical models.
AB  - To characterize post-treatment clearance of young forms of Plasmodium falciparum
      from the blood, three differential equation models, a linear decline, a linear
      then logarithmic decline, and the Michaelis-Menten (MM) kinetic equation, were
      fitted to log-transformed serial parasite counts from 30 semi-immune patients
      with synchronous parasitaemias allocated one of six antimalarial drug regimens.
      The first two equations were solved analytically. The MM equation was solved
      numerically using a fifth-order Runge-Kutta method. For each equation, parasite
      clearance was assumed stochastic and log-transformed parasite counts were assumed
      to be normally distributed at each time-point. Comparisons between models were by
      Minimum Akaike Information Criterion Estimate. A constrained MM equation fitted
      the data at least as well as the other two models in 5 of 6 drug groups and also
      when pooled data were analysed, providing a single index which could be used in
      drug efficacy studies in similar situations or as part of more complex models
      that encompass asynchronous, complicated infections.

PMID- 9287948
TI  - Acute hepatitis B in Edinburgh 1975-92: a retrospective study in a population
      where human immunodeficiency virus is highly prevalent.
AB  - A retrospective study of notified hepatitis B virus (HBV) infection in Edinburgh
      during 1975-92 identified 525 acute cases. For 343 where a probable transmission
      route could be determined, 215 were due to shared equipment by injection drug
      users (IDUs), 29 to homosexual intercourse, 25 to heterosexual or household
      contact with IDUs, 21 to heterosexual contact with infected non-IDU partners and
      53 to various other or multiple routes. Cases were unevenly distributed
      geographically, particularly those among IDUs. The highest incidence within a
      post code district was approximately 2.5 times that for all Edinburgh. Annual
      cases peaked in 1984 then declined to low levels in the early 1990s. This
      reduction was most marked among IDUs, and may be ascribed both to changed
      injecting behaviour and decreased susceptibility within this group. The latter
      factor implies that HBV infections may be an unreliable guide to human
      immunodeficiency virus (HIV) infection in populations where HBV is highly
      prevalent.

PMID- 9287949
TI  - A computer simulation of the transmission dynamics and the effects of duration of
      immunity and survival of persistently infected animals on the spread of bovine
      viral diarrhoea virus in dairy cattle.
AB  - This paper describes a computer model that mimics the spread of bovine viral
      diarrhoea virus (BVDV) infection through a closed herd. The model is able to
      simulate the spread of infection when a persistently infected (PI) animal is
      introduced into an infection-free herd, and it is used to investigate the role of
      persistently infected animals, seroconverting animals, loss of PI calves and
      duration of immunity on the level of infection within the herd. Under typical
      management conditions one persistently infected animal poses a real threat to a
      herd, and the prospect of the herd becoming infection free in a 10-year period
      without intervention is remote. Seroconverting animals are found to be an
      important source of infection in herds with few immune animals. The increased
      loss of PI calves is likely to restrict the numbers of PI animals in a herd, and
      loss of immunity is important since it increases the possibility of a PI calf
      being born.

PMID- 9287950
TI  - The stimulating effect of fosfomycin, an antibiotic in common use in Japan, on
      the production/release of verotoxin-1 from enterohaemorrhagic Escherichia coli
      O157:H7 in vitro.
AB  - In 1996 Japan had a big outbreak of enterohaemorrhagic Escherichia coli (EHEC)
      O157:H7, especially in Osaka prefecture where about 6000 patients (mainly
      schoolchildren) suffered from diarrhoea, haemorrhagic colitis and haemolytic
      uraemic syndrome (HUS) due to EHEC infection via school lunch. Our survey of
      doctors who took care of those patients showed that most patients had received
      antibiotics, especially fosfomycin which comprised 84% of the prescribed
      treatment. Since the administration of antibiotics for EHEC infection is under
      discussion, we analysed the effect of fosfomycin on production/release of
      verotoxins (VTs). Addition of fosfomycin into EHEC culture in CAYE broth at 2 and
      5 h after start of incubation caused marked increase of VT1 release. This
      observation warns of the possibility of fosfomycin treatment making the disease
      worse.

PMID- 9287951
TI  - Cryptosporidium parvum: oocyst excretion and viability patterns in experimentally
      infected lambs.
AB  - Cryptosporidium parvum infections of domestic animals can have a considerable
      economic impact and as oocysts are voided in the faeces of infected hosts,
      environmental contamination with agricultural waste has also become a matter of
      concern. Since only viable oocysts are potentially infectious, the numbers of
      oocysts excreted during infection can have important implications for both
      veterinary and public health. During the course of infection in experimentally
      infected lambs, oocyst viability was assessed by a fluorogenic vital dyes assay
      and by a maximized in vitro excystation assay. The excreted oocyst populations
      contained a higher proportion of viable oocysts 5-11 days post infection (d.p.i.)
      than later in the infection. Oocyst viability declined consistently 11-15 d.p.i.
      and coincided with periods when peaks in serum and intestinal anti
      Cryptosporidium antibodies have been reported to occur. Infected lambs excreted a
      mean of 4.8 (standard error [S.E.] +/- 0.4) x 10(9) oocysts per g of faeces, of
      which half were non-viable and therefore of no significance for disease
      transmission. This study demonstrates that the numbers of viable oocysts excreted
      by infected lambs is smaller than previously suspected.

PMID- 9287952
TI  - Leishmania infantum promastigotes: flow cytometry as a possible tool for
      assessing the effects of drugs on cellular functions.
AB  - The capacity of flow-cytometric techniques to detect drug-specific biochemical
      targets and side effects in Leishmania infantum promastigotes was estimated by
      assessing the effects of three antileishmanial drugs (pentamidine, allopurinol,
      and amphotericin B) on parasite metabolism. Cell cycle and total protein content
      were estimated by staining cells with propidium iodide and fluorescein
      isothiocyanate, nonprotein thiols were stained by mercury orange, and membrane
      potential was measured by the accumulation of 3,3'-dipenthyloxacarbocyanine
      iodide inside the cell. Results showed that dynamic studies in parasites treated
      with subtoxic concentrations of drugs allowed the detection of drug-specific
      targets: pentamidine primarily affected nonprotein thiol contents and DNA
      synthesis, allopurinol primarily affected intracellular protein contents, and
      amphotericin B primarily affected membrane potential. Moreover, the assessment of
      cellular functions in parasites treated with increasing concentrations of drugs
      certified the capacity of these techniques to establish dose-response curves and
      to permit the detection of side effects.

PMID- 9287954
TI  - Brugia pahangi: differential induction and regulation of jird inflammatory
      responses by life-cycle stages.
AB  - It has been hypothesized that different life-cycle stages of filarial nematodes
      induce different host responses. This concept was examined in the Brugia pahangi
      jird model of lymphatic filariasis by measuring the kinetics of inflammatory
      responses to parasite antigens following intraperitoneal inoculation of different
      life-cycle stages. For this purpose, viable female or male worms, L3, L4, or
      microfilarial stage, were used. Dead worms served as controls. Worm and
      microfilarial burdens, pulmonary granulomatous inflammation (PGRN) to soluble
      adult worm antigen (SAWA)-coated beads, and peritoneal eosinophil and macrophage
      numbers were assessed at different days post-inoculation. All jirds inoculated
      with any of these life-cycle stages developed an early PGRN to SAWA which was
      later significantly reduced. Only viable worms induced down-regulation of the
      PGRN response. These results indicate that the hyporesponsive state is induced
      and maintained by all life-cycle stages. Also, the degree of granulomatous
      response was influenced by worm burden, with larger worm burdens inducing lower
      initial levels of PGRN to SAWA. Peritoneal inflammatory responses differed from
      the systemic response in that numbers of macrophages increased with time and
      microfilarial accumulation. No correlation was observed between peritoneal
      inflammatory responses measured by eosinophil and macrophage numbers and PGRN to
      SAWA.

PMID- 9287953
TI  - Trypanosoma cruzi: nitrogenous-base-containing phosphatides in trypomastigote
      forms--isolation and chemical analysis.
AB  - In trypanosomatids, little is known about the biosynthetic pathways involved in
      the metabolism of ethanolamine. In an attempt to clarify this point, an
      exhaustive analysis of the chloroform:methanol extract of T. cruzi
      trypomastigotes metabolically labeled with [14C]ethanolamine, in comparison with
      the lipids from [3H]palmitic acid-incorporated parasites, was performed. In both
      cases, phosphatidylethanolamine and lysophosphatidylethanolamine were detected,
      while phosphatidylcholine and lysophosphatidylcholine were only labeled with the
      fatty acid precursor. However, dimethylphosphatidylethanolamine was isolated from
      parasites labeled with the base precursor, indicating the ability of trypanosomes
      to methylate phosphatidylethanolamine to dimethylphosphatidylethanolamine. Fatty
      acids of the labeled phospholipids were analyzed by reverse-phase thin-layer
      chromatography and fluorography. Interestingly, phospholipids from the
      trypomastigote stage show palmitic acid (C16:0) and stearic acid (C18:0) as the
      only labeled components. The same saturated fatty acids were found free and as
      components of the radioactive triglycerides. No unsaturated fatty acids were
      detected, in accordance with the results obtained with inositolphospholipids.
      Conversely, when the fatty acids of phospholipids purified from nonlabeled
      parasites were analyzed by gas-liquid chromatography and gas-liquid
      chromatography-mass spectrometry, C18:1 was also detected. A striking finding was
      the presence of a considerable amount of free lignoceric acid (C24:0). Also, the
      C24:0 fatty acid was identified in the triglyceride fraction and as a component
      of phosphatidylcholine. The limited capacity of trypomastigote forms to elongate
      fatty acids was determined. In contrast with the results reported for other
      noninfective forms of the parasite, the absence of unsaturated fatty acids due to
      a low activity of desaturases was observed.

PMID- 9287955
TI  - Isolation and characterization of americanin, a specific inhibitor of thrombin,
      from the salivary glands of the lone star tick Amblyomma americanum (L.).
AB  - A thrombin (EC 3.4.21.5) inhibitor (americanin) was isolated from the salivary
      glands of the lone star tick Amblyomma americanum (L.) using reversed-phase
      chromatography and anion-exchange chromatography. Americanin did not inhibit any
      other protease tested, including factor Xa, plasmin, trypsin, chymotrypsin,
      elastase, papain, pepsin, and carboxypeptidase. The inhibition of thrombin by
      americanin decreased dramatically with dilution of the reaction mixture including
      thrombin, its substrate, and americanin. When thrombin assays were performed in
      the presence of americanin, the reaction curve showed a time-dependent
      inhibition. Significant inhibition was observed when americanin concentration was
      approximately equal to that of thrombin, with a Ki of 0.073 nM. The results
      suggest that americanin is a specific, reversible, competitive, slow, tight
      binding inhibitor of thrombin.

PMID- 9287959
TI  - Echinococcus granulosus: cloning and characterization of a tandemly repeated DNA
      element.
AB  - A repetitive DNA element from the genome of the cestode Echinococcus granulosus
      has been cloned and sequenced. The 186-base-pair repeating units are arranged in
      direct tandem, probably clustered in the parasite genome. The estimated copy
      number of the repeat is 11,500 and represents between 2 and 3% of the parasite
      genome. The repetitive sequence is specific for Echinococcus since it does not
      cross-hybridize with either DNA of other cestode species or pig and dog DNA. The
      repetitive element is capable of detecting between 250 and 500 pg of E.
      granulosus DNA by dot blot assay.

PMID- 9287956
TI  - Plasmodium falciparum: sickle-cell trait is associated with higher prevalence of
      multiple infections in Gabonese children with asymptomatic infections.
AB  - Through PCR amplifications of the gene encoding the merozoite surface antigen 2,
      utilizing allele-specific 3D7 and FC27 probes, we have examined the prevalence of
      Plasmodium falciparum in children aged from 7 to 14 years living in a village
      located in the equatorial forest region of Central Africa (Gabon). Using this
      technique, 61% (100/163) of the blood samples were shown to be infected with P.
      falciparum with 24 alleles distinguished by size polymorphism and sequence type.
      The two main families (3D7 and FC27) and hybrid alleles were detected regardless
      of sex and hemoglobin phenotype. No age-related changes in prevalence of P.
      falciparum strains were observed; however, the prevalence of infection (42%) was
      significantly lower in individuals with the sickle-cell trait compared with their
      normal-hemoglobin counterparts (68%). Mixtures of genetically distinct parasite
      clones were present in 82% of children carrying the sickle-cell trait but in only
      58% of normal-hemoglobin carriers. The significance of these observations
      regarding the design and interpretation of epidemiological investigations is
      discussed in the context of malaria transmission in the region studied.

PMID- 9287958
TI  - Trypanosoma cruzi: T cell subpopulations in the Peyer's patches of BALB/c
      infected mice.
AB  - The changes in the T cell subsets of the Peyer's patches and the thymus were
      analyzed in BALB/c mice infected with Trypanosoma cruzi, Tulahuen strain. During
      the acute stage of the infection both lymphoid organs drastically reduced their
      cellularity. This was mainly due to the decrease in the immature CD4+CD8+ T cell
      population in the thymus and in both T and B cells in the Peyer's patches. In the
      acute infection, few Peyer's patches were found and the histological studies
      revealed a depletion of the thymic-dependent areas, paralleling the decreased
      number of cells expressing CD4 and alpha beta T cell receptor. After 14 weeks, in
      the late stage of the infection, the cellularity and the levels of the T cell
      subsets studied returned to values similar to those of noninfected mice.

PMID- 9287961
TI  - Trichomonas vaginalis: analysis of codon usage.

PMID- 9287957
TI  - Leishmania major: a clone with low virulence for BALB/c mice elicits a Th1 type
      response and protects against infection with a highly virulent clone.
AB  - BALB/c mice are highly susceptible to infection with Leishmania major and
      generally develop a severe, nonhealing form of disease following parasite
      inoculation. As opposed to protective Th1 type immune responses which develop in
      resistant strains of mice, BALB/c mice develop predominant Th2 type responses
      characterized by the production of high levels of IL-4, but only low levels of
      IFN-gamma. However, BALB/c mice will develop resistance and Th1 type responses
      following the inoculation of very low numbers of L. major promastigotes. In this
      study, we have examined the effects of parasite virulence on the immune response
      and disease phenotype in susceptible BALB/c mice. Two clones of L. major were
      isolated which differed with respect to their in vitro growth rates as
      promastigotes and their virulence for mice. One rapidly growing clone, L.m.F1,
      was highly virulent in BALB/c mice and produced nonhealing infections
      characterized by predominant Th2 type responses. In contrast, a slow-growing
      clone, L.m.S2, was less virulent in BALB/c mice and produced self-healing
      infections at parasite doses equivalent to those which produced progressive
      disease with the more virulent clone. Mice which healed infections with the
      L.m.S2 clone developed responses characterized by elevated production of IFN
      gamma and were resistant to a challenge infection with the virulent L.m.F1 clone.
      These results suggest that the virulence of individual parasite clones may
      influence both the course of disease and the phenotype of the immune response
      which develops during infection.

PMID- 9287962
TI  - Image of the month. Pancreas divisum.

PMID- 9287960
TI  - Plasmodium falciparum: soluble thrombospondin increases cytoadherence of
      parasitized erythrocytes to human microvascular endothelium under shear flow
      conditions.

PMID- 9287963
TI  - 24-hour gastric pH and extent of duodenal gastric metaplasia in Helicobacter
      pylori-positive patients.
AB  - BACKGROUND & AIMS: Gastric metaplasia (GM) is essential to explain duodenal
      colonization by Helicobacter pylori. It seems to be acid induced but also occurs
      in H. pylori-positive patients with nonulcer dyspepsia (NUD), who are not acid
      hypersecretors. The aim of this study was to assess the circadian gastric acidity
      of 47 patients with duodenal ulcers (DUs) and 32 patients with NUD, both H.
      pylori positive, and its correlation to duodenal GM extent. METHODS: H. pylori
      was detected by histology and CLOtest, and GM was diagnosed and graded on four
      bulb biopsy specimens. Each patient underwent 24-hour gastric pH-metry, and the
      relation between gastric pH and GM extent was assessed by factorial analysis.
      RESULTS: Gastric pH was greater in patients with NUD than in patients with DU
      during 24 hours, night and daytime (P < 0.03-0.005). Gastric pH differed
      significantly (P < 0.0002) in relation to GM extent between the two populations,
      whereas no difference was found among the pH values of GM degrees. A significant
      increase in 24-hour gastric pH was associated with greater GM in patients with
      DU, whereas the opposite occurred in patients with NUD (P < 0.007). CONCLUSIONS:
      The lower gastric acidity in patients with NUD than in patients with DU and the
      lack of correlation between gastric pH and the various GM degrees in the two H.
      pylori-positive populations suggest that gastric hyperacidity is not associated
      with duodenal GM.

PMID- 9287965
TI  - Comorbid occurrence of laryngeal or pulmonary disease with esophagitis in United
      States military veterans.
AB  - BACKGROUND & AIMS: It has been speculated that gastroesophageal reflux disease
      (GERD) represents a risk factor for the occurrence of extraesophageal
      complications. The aim of this study was to compare the comorbid occurrence of
      sinus, laryngeal, and pulmonary diseases in case subjects with and control
      subjects without reflux esophagitis. METHODS: The case population consisted of
      all patients with erosive esophagitis (International Classification of Diseases
      code 530.1) or esophageal stricture (ICD code 530.3) who were discharged from
      hospitals of the Department of Veteran Affairs between 1981 and 1994. In
      multivariate logistic regressions, the occurrence of sinus, pharyngeal,
      laryngeal, or pulmonary disease was compared between cases with and an equal
      number of controls without esophagitis or stricture. RESULTS: A total of 101,366
      case subjects was analyzed. Erosive esophagitis and esophageal stricture were
      associated with sinusitis (odds ratio, 1.60; 95% confidence interval, 1.51-1.70),
      pharyngitis (1.48; 1.15-1.89), aphonia (1.81; 1.18-2.80), laryngitis (2.01; 1.53
      2.63), laryngeal stenosis (2.02; 1.12-3.65), chronic bronchitis (1.28; 1.22
      1.34), asthma (1.51; 1.43-1.59), chronic obstructive pulmonary disease (1.22;
      1.16-1.27), pulmonary fibrosis (1.36; 1.25-1.48), bronchiectasis (1.26; 1.09
      1.47), pulmonary collapse (1.31; 1.23-1.40), and pneumonia (1.15; 1.12-1.18).
      CONCLUSIONS: Patients with reflux esophagitis are at an increased risk of
      harboring a large variety of sinus, pharyngeal, laryngeal, and pulmonary
      diseases.

PMID- 9287964
TI  - Mast cell involvement in gastritis with or without Helicobacter pylori infection.
AB  - BACKGROUND & AIMS: Mast cells are initiators and regulators of inflammation, but
      their role in the human stomach remains unclear. Therefore, the extent and
      distribution of mast cell involvement in gastritis with or without Helicobacter
      pylori infection was investigated. METHODS: Mapped biopsy specimens from 17 H.
      pylori-positive and 20 H. pylori-negative subjects were examined. Sections were
      assessed for infection and inflammation and stained with anti-human mast cell
      tryptase to count mucosal and epithelial mast cells. Density of mast cells in
      different gastric compartments, their response to infection treatment, and their
      relationship with other inflammatory cells were evaluated. Mast cell
      degranulation was evaluated by electron microscopy. RESULTS: Mast cell density
      was significantly greater in the mucosa with gastritis, with or without H. pylori
      infection, than in the mucosa of noninfected normal subjects. In the antrum,
      density was much greater in H. pylori-infected peptic ulcer subjects than in the
      other gastritis groups. It also correlated significantly with the intensity of
      inflammation. Mast cell degranulation was demonstrated by electron microscopy in
      H. pylori-infected mucosa. Mast cell density in ulcer patients decreased
      significantly after cure of H. pylori infection. CONCLUSIONS: Mast cells may be
      important effector cells in the pathogenesis of gastritis, especially in H.
      pylori-associated peptic ulcer.

PMID- 9287966
TI  - Prognostic value of chromosome 1p allelic loss in colon cancer.
AB  - BACKGROUND & AIMS: Current evidence suggests that there may be a tumor-suppressor
      gene on chromosome 1p associated with colorectal cancer. The aim of the present
      study was to determine whether allelic loss on chromosome 1p is of prognostic
      value in colorectal cancer. METHODS: Polymerase chain reaction was used to assess
      allelic loss of five chromosome 1p microsatellite markers in tumor specimens.
      Genomic DNA was prepared from archival tumor and corresponding normal tissue
      specimens from 116 patients who had undergone curative treatment for
      adenocarcinoma of the colon. Allelic loss was correlated with disease-free
      interval and survival. RESULTS: Deletion of 1p sequence was detected in 22 of 82
      tumors. Deletions of the microsatellite markers D1S228 (1p36) and HY-TM1 (1p32)
      were significantly associated with poor survival (P < 0.05): relative risk, 4.1;
      95% confidence interval, 1.25-9.23 for D1S228; and relative risk, 6.6; 95%
      confidence interval, 1.4-19 for HY-TM1. Loss of heterozygosity at D1S228 was also
      associated with shorter disease-free interval: relative risk, 4.5; 95% confidence
      interval, 1.3-11. CONCLUSIONS: Allelic loss in the 1p36 and 1p32 regions of
      chromosome 1 appears to be an independent predictor of poor prognosis in patients
      with adenocarcinoma of the colon.

PMID- 9287967
TI  - Inhibition of tumor cell kinetics and serum insulin growth factor I levels by
      octreotide in colorectal cancer patients.
AB  - BACKGROUND & AIMS: Octreotide was shown to inhibit the growth of colon cancer and
      to reduce serum concentrations of tumor growth factors such as insulin-like
      growth factor I (IGF-I) and epidermal growth factor (EGF) in vitro and in animal
      models. Effects of octreotide on tumor cell kinetics and serum concentration of
      IGF-I and EGF in patients with colorectal cancer were evaluated. METHODS: Seventy
      five patients with colorectal cancer were randomized to receive octreotide (200
      micrograms daily) in the 2 weeks before surgery or the usual medications. Samples
      of tumor tissue were taken at endoscopy and at surgery. [3H]Thymidine labeling
      index and flow cytometry were used to assess the S-phase fraction. In octreotide
      treated patients, plasma levels of IGF-I, EGF, and growth hormone were assessed
      before and after treatment. RESULTS: There was a statistically significant
      reduction in the mean percentage of the S-phase fraction as a result of
      octreotide treatment measured by both [3H]thymidine labeling index (P = 0.001)
      and flow cytometry (P = 0.001). No reduction in the percentage of the S-phase
      fraction was observed in the control group patients. Serum values of IGF-I were
      significantly reduced by octreotide, whereas EGF and growth hormone levels were
      not affected. CONCLUSIONS: Octreotide reduces the proliferative activity of tumor
      cells and the serum IGF-I levels in patients with colorectal cancer. This
      activity may have a role in the treatment of colorectal cancer.

PMID- 9287968
TI  - The multiple endocrine neoplasia type I gene locus is involved in the
      pathogenesis of type II gastric carcinoids.
AB  - BACKGROUND & AIMS: Both gastrin and genetic factors were suggested to underlie
      the pathogenesis of multiple gastric enterochromaffin-like (ECL) cell carcinoids.
      To assess the role of genetic alterations in carcinoid tumorigenesis, loss of
      heterozygosity (LOH) at the locus of the multiple endocrine neoplasia type 1 (MEN
      1) gene was studied in gastric carcinoids of patients with MEN-1 and chronic
      atrophic type A gastritis (A-CAG), as well as in sporadically arising intestinal
      carcinoids. METHODS: DNA extracted from archival tissue sections of 35 carcinoid
      tumors was assessed for LOH with eight polymorphic markers on chromosome 11q13. A
      combined tumor and family study was performed in 1 patient with MEN-1-Zollinger
      Ellison syndrome (ZES). RESULTS: LOH at 11q13 loci was detected in 15 of 20 (75%)
      MEN-1-ZES carcinoids, and each ECL-cell carcinoid with LOH showed deletion of the
      wild-type allele. Only 1 of 6 A-CAG carcinoids displayed LOH at the MEN-1 gene
      locus, and none of the 9 intestinal and rectal carcinoids showed 11q13 LOH.
      CONCLUSIONS: Gastric ECL-cell carcinoid is an independent tumor type of MEN-1
      that shares a common developmental mechanism (via inactivation of the MEN-1 gene)
      with enteropancreatic and parathyroid MEN-1 tumors. Further analysis of sporadic
      and A-CAG carcinoids is needed to elucidate genetic factors involved in their
      tumorigenesis.

PMID- 9287978
TI  - Intestinal absorption of proline and leucine in chronically catheterized rats.
AB  - BACKGROUND & AIMS: Most studies of intestinal amino acid absorption use methods
      in which intestinal function is studied immediately after surgical manipulation.
      The unphysiological experimental conditions present in these studies limit the
      ability to extrapolate their results to normal physiological conditions. The aim
      of this study was to determine the rates of proline and leucine absorption under
      normal physiological conditions. METHODS: Absorption of proline and leucine was
      measured in long-term catheterized rats using a method of dual infusion of
      radiolabeled isotopes. RESULTS: The maximum transport velocity and apparent
      membrane permeability for proline were 16.1 mumol/ min and 0.07 mumol.min
      1.mmol/L-1. For leucine, the maximum transport velocity and apparent membrane
      permeability were 14.9 mumol/min and 0.08 mumol.min-1.mmol/L-1. Surgical bowel
      manipulation decreased the maximum transport velocities for proline and leucine
      by > 80%. The adverse effects of surgery were present for 24 hours. CONCLUSIONS:
      Under normal physiological conditions, most proline and leucine is absorbed by
      active transport. Measurements of amino acid absorption using methods in which
      the intestine has been surgically manipulated within the previous 24 hours
      significantly underestimate proline and leucine absorption and do not reflect
      absorption under normal physiological conditions.

PMID- 9287969
TI  - Regulation of growth of human gastric cancer by gastrin and glycine-extended
      progastrin.
AB  - BACKGROUND & AIMS: Gastrin (G-17) stimulates the growth of certain gastric and
      colon cancers mostly through gastrin/cholecystokinin (CCK)-B receptors. Glycine
      extended gastrin (Gly-G) stimulates growth of a rat pancreatic acinar cell line;
      however, the effect of Gly-G on human gastric cancers is not known. The purpose
      of this study was to characterize the trophic effect of G-17 and Gly-G on two
      human gastric cancer cell lines, AGS and SIIA. METHODS: Binding analyses were
      performed, and cell growth was assessed by counting cells over a time course.
      RESULTS: G-17 stimulated growth of both AGS and SIIA cells. In AGS cells,
      gastrin/CCK-B receptor antagonists inhibited the effect of G-17 and competitively
      antagonized 125I-G-17 binding, whereas the CCK-preferring (CCK-A) receptor
      antagonists had no effect. In contrast, CCK-A receptor antagonists inhibited the
      stimulatory effect of G-17 in SIIA cells, whereas CCK-B receptor antagonists had
      no effect. Gly-G stimulated the growth of AGS and SIIA cells; neither the CCK-B
      nor the CCK-A receptor antagonists blocked this effect. CONCLUSIONS: G-17
      stimulates proliferation of AGS cells through the CCK-B receptor; however, G-17
      mediated growth of SIIA acts through a CCK-A-like receptor. Furthermore, Gly-G
      stimulates growth of human gastric cancer cell lines, possibly through a receptor
      other than the CCK-B or CCK-A receptor.

PMID- 9287970
TI  - Chromosomal alterations in ulcerative colitis-related neoplastic progression.
AB  - BACKGROUND & AIMS: It is unclear whether genomic derangement precedes the
      histological development of dysplasia in ulcerative colitis (UC)-related
      neoplastic progression. The primary aim of this study was to determine if
      chromosomal alterations occur early in the progression pathway of UC-related
      neoplasia. METHODS: Fluorescence in situ hybridization (FISH) was performed on
      nuclei dissociated from sites of cancer, dysplasia, and UC-involved nondysplastic
      epithelium in five UC-related cancer colectomy specimens using a panel of
      pericentromeric probes. Comparative genomic hybridization (CGH) was used to
      detect clonal chromosomal losses and gains in DNA extracted from these sites.
      RESULTS: FISH analysis revealed significant and often dramatic alterations in
      chromosome copy number compared with controls in all biopsy specimens of cancer,
      dysplasia, and nondysplastic UC-involved epithelium. Clonal chromosomal losses
      and gains were detected by CGH in all but one analyzed site of dysplasia and
      cancer and in two of the five nondysplastic sites. FISH and CGH frequently
      detected the relative loss of chromosome 18. CONCLUSIONS: Chromosomal alterations
      may occur early in UC-related neoplastic progression and seem to precede the
      histological development of dysplasia. Relative loss of 18q may be important in
      the progression of UC-related neoplasia. The detection of chromosomal alterations
      as an intermediate end point may prove useful in identifying patients at high
      risk for the development of colorectal cancer.

PMID- 9287973
TI  - Autocrine regulation of growth in cultured human intestinal muscle by growth
      factors.
AB  - BACKGROUND & AIMS: Transforming growth factor (TGF)-alpha, insulin-like growth
      factor (IGF)-I, and TGF-beta 1 are expressed in vivo by intestinal smooth muscle.
      The aim of this study was to determine whether these growth factors were produced
      by human intestinal muscle cells in culture and to identify their roles in
      regulating growth. METHODS: Muscle cells were examined at various times in
      culture: during rapid growth (day 3), at confluence (day 7), and after confluence
      (day 14). Growth factor production was measured by radioimmunoassay or enzyme
      linked immunosorbent assay. Growth was measured from [3H]thymidine incorporation.
      RESULTS: Production of pro-TGF-alpha and TGF-alpha (1550 +/- 100 and 1260 +/- 150
      pg/mg protein, respectively) and free IGF-I (86.2 +/- 23.7 ng/mg protein) was
      highest during rapid growth and 3-40-fold lower later in culture. Production of
      soluble and latent TGF-beta 1 was highest in postconfluent cells (280 +/- 74 and
      4320 +/- 610 pg/mg protein, respectively) and 4-7-fold lower earlier in culture.
      TGF-alpha and IGF-I caused concentration-dependent stimulation of growth in
      rapidly growing cells. TGF-beta 1 caused concentration-dependent inhibition of
      growth predominantly in postconfluent cells. Neutralizing antibodies to TGF-alpha
      or IGF-I inhibited growth and neutralizing antibody to TGF-beta augmented growth.
      CONCLUSIONS: Human intestinal muscle cells produce TGF-alpha, IGF-I, and TGF-beta
      1 in a time-dependent reciprocal fashion that parallels their effects on growth.

PMID- 9287972
TI  - The C-X-C chemokine ENA-78 is preferentially expressed in intestinal epithelium
      in inflammatory bowel disease.
AB  - BACKGROUND & AIMS: Secretion of chemokines by epithelial cells may represent a
      crucial event in the pathogenesis of inflammatory bowel disease (IBD). Expression
      of the chemokine epithelial neutrophil-activating peptide 78 (ENA-78) was
      monitored in patients with IBD and normal controls. METHODS: In situ
      hybridizations were performed on 41 tissue specimens from 15 patients with IBD
      and 10 controls to detect ENA-78 messenger RNA (mRNA). Immunofluorescence
      stainings were used to localize ENA-78 protein. RESULTS: Intestinal epithelial
      cells expressing ENA-78 mRNA at detectable levels are found at comparable
      frequencies in patients with Crohn's disease and ulcerative colitis. Tissue
      specimens with mild to moderate histological signs of disease activity show
      slightly higher frequencies of ENA-78 mRNA-expressing epithelial cells than areas
      with signs of severe disease activity (P = 0.14). Immunofluorescence stainings
      showed presence of the ENA-78 protein in > 90% of preserved epithelial cells in
      IBD, in control tissues, ENA-78 mRNA was not detectable, and ENA-78 protein was
      detectable in 0%-30% of epithelial cells. CONCLUSIONS: The observations are in
      agreement with a role of the C-X-C chemokine ENA-78 in the pathogenesis of IBD.

PMID- 9287977
TI  - Rapid transepithelial antigen transport in rat jejunum: impact of sensitization
      and the hypersensitivity reaction.
AB  - BACKGROUND & AIMS: Intestine from sensitized rats develops a rapid secretory
      response to luminal antigen challenge that depends on activation of subepithelial
      mast cells. The aim of this study was to determine the timing and route of the
      transepithelial protein antigen transport. METHODS: Rats were sensitized to
      horseradish peroxidase (HRP). After 10-14 days, jejunal segments were resected,
      mounted in Ussing chambers, and challenged with HRP on the luminal side. RESULTS:
      Electron microscopy of tissue specimens fixed at 2 minutes (before mast cell
      activation) showed enhanced endocytic uptake of HRP in enterocytes of HRP
      sensitized rats compared with ovalbumin-sensitized or saline-injected controls.
      At this time, HRP was distributed throughout epithelial cells and was already
      evident in the lamina propria. In contrast, HRP was restricted to the apical
      region of enterocytes in controls. At 30 minutes (after mast cell activation), in
      HRP-sensitized rats only, HRP was also located within tight junctions and the
      paracellular region between epithelial cells. Tissue conductance was increased in
      HRP-sensitized rats beginning 30 minutes after HRP addition and correlated with
      the overall flux of HRP across the tissue. CONCLUSIONS: The results show that
      specific sensitization enhances the initial uptake and transcytosis of antigen
      across intestinal epithelium. Subsequent to activation of mast cells, antigen
      transport is further enhanced by penetration through the paracellular pathway.

PMID- 9287979
TI  - Luminal acid increases apical cell membrane resistance in isolated Necturus
      antral mucosa.
AB  - BACKGROUND & AIMS: The gastric mucosa must have efficient protective mechanisms
      to maintain physiological intracellular pH. The aim of this study was to
      investigate the effect of low luminal pH on apical membrane permeability.
      METHODS: Chambered Necturus antral mucosa was perfused with Ringer's/95% O2-5%
      CO2 at pH 7.25. The mucosal side was exposed to pH 4.0-2.0 with four
      microelectrodes placed in surface cells. Two-dimensional cable analysis was used
      to measure apical, basolateral, and shunt resistances. In some experiments,
      liquid sensor pH or Na(+)-selective microelectrodes were used. RESULTS: Luminal
      acidification hyperpolarized apical cell membrane potential and increased apical
      cell membrane resistance from 21.3 +/- 2.6 (pH 7.25) to 38.0 +/- 2.3 k omega.cm2
      (pH 3.0; n = 8). The increase in apical cell membrane resistance was preceded by
      transient intracellular acidosis from 7.32 +/- 0.07 (pH 4.0) to 7.23 +/- 0.06 (pH
      3.0; n = 6). Similar intracellular acidosis (provoked by NH4+ prepulse) failed to
      cause the effects observed with luminal acid. The increase in apical cell
      membrane resistance caused by luminal acid was eliminated when N-methyl-D
      glucamine+, but not Na+, was substituted for all cations in the luminal solution.
      CONCLUSIONS: Luminal acidification (pH 3.0-2.0) closes apical amiloride-blockable
      Na+ channels. Protons are probably able to pass and even block these channels,
      but their effect in closing the channels does not occur intracellularly.

PMID- 9287974
TI  - Mice lacking transforming growth factor alpha have an increased susceptibility to
      dextran sulfate-induced colitis.
AB  - BACKGROUND & AIMS: There is indirect evidence that transforming growth factor
      alpha (TGF-alpha) is an important mediator of mucosal defense and repair. TGF
      alpha knockout mice and TGF-alpha-deficient mice (wa-1) provide novel approaches
      to evaluate the role of TGF-alpha in preserving the integrity of the colon.
      METHODS: Colitis was induced by oral administration of dextran sodium sulfate
      (DSS, 5 g/dL) to knockout mice, their genetic controls (GC), wa-1 mice, and
      BALB/c mice. TGF-alpha was also administered intraperitoneally to wa-1 mice to
      evaluate the effect of exogenous TGF-alpha in DSS colitis. RESULTS: In response
      to DSS, nearly 60% of the entire colonic mucosa was destroyed in knockout and wa
      1 mice, compared with 22% in GC mice and 16% in BALB/ c mice. Body weight loss
      was doubled in knockout (28%) and wa-1 mice (23%) compared with GC (11%) and
      Balb/c mice (12%). TGF-alpha application to wa-1 mice reduced the severity of
      mucosal injury by almost 70% compared with controls. CONCLUSIONS: The marked
      susceptibility of TGF-alpha knockout and wa-1 mice to DSS and the obvious
      amelioration of the colonic injury by exogenous TGF-alpha application in wa-1
      mice suggest that TGF-alpha is a mediator of protection and/or healing mechanisms
      in the colon.

PMID- 9287976
TI  - Rat lactase-phlorizin hydrolase/human growth hormone transgene is expressed on
      small intestinal villi in transgenic mice.
AB  - BACKGROUND & AIMS: Lactase-phlorizin hydrolase (LPH) is an absorptive enterocyte
      specific gene that is expressed in a well-characterized pattern along the
      cryptvillus (vertical), proximal-distal (horizontal), and developmental
      (temporal) gradients. The aim of this study was to characterize the capacity of
      regulatory elements within the rat LPH gene to direct appropriate cell lineage
      and topographical patterns of expression in vivo in transgenic mice. METHODS:
      Transgenic mouse lines were established using a construction containing bases 
      2038 to +15 of the rat LPH gene fused to a human growth hormone reporter gene.
      RESULTS: In one line, the transgene was expressed only in small intestine and was
      localized to absorptive enterocytes on villi. The transgene was not expressed in
      goblet or enteroendocrine cells or in crypts. Transgene expression along
      horizontal and developmental gradients was different from that of the native
      mouse LPH gene. CONCLUSIONS: The results suggest that the region from -2038 to
      +15 of the rat LPH gene contains regulatory elements that direct correct tissue,
      cell, and vertical expression but may not contain all the elements necessary for
      appropriate horizontal and temporal control. This investigation provides further
      insight into the complexities of the molecular control of intestinal gene
      expression.

PMID- 9287975
TI  - Distribution of cell adhesion molecules in infants with intestinal epithelial
      dysplasia (tufting enteropathy).
AB  - BACKGROUND & AIMS: Intestinal epithelial dysplasia, or tufting enteropathy, is a
      newly described clinicopathologic entity with refractory diarrhea in infants.
      Histological abnormalities include villous atrophy, disorganization of the
      surface epithelium, and basement membrane abnormalities. The aim of this study
      was to examine defects in intestinal epithelial cell adhesion, differentiation,
      or proliferation in the pathogenesis of epithelial dysplasia. METHODS:
      Histological, immunohistochemical, and ultrastructural characteristics of
      epithelial dysplasia in a group of 6 children were compared with those groups
      with normal small bowel and other villous atrophy (celiac sprue and microvillous
      inclusion disease). Distribution of adhesion molecules, markers of cell
      polarization and proliferation, and the phenotype of intraepithelial lymphocytes
      were determined. RESULTS: Alterations suggestive of abnormal cell-cell and cell
      matrix interactions were present in patients with epithelial dysplasia. They
      included abnormal distribution of alpha 2 beta 1 integrin along the crypt-villus
      axis, increased immunohistochemical expression of desmoglein, and ultrastructural
      changes of desmosomes increased in length and number. No evidence for
      abnormalities in epithelial cell polarization, proliferation, or T-cell
      activation was found. CONCLUSIONS: This study strongly suggests a role played by
      alterations of cell-cell and cell-matrix interactions in the pathogenesis of
      epithelial dysplasia.

PMID- 9287971
TI  - Clustering of increased small intestinal permeability in families with Crohn's
      disease.
AB  - BACKGROUND & AIMS: Small intestinal permeability is increased in a proportion of
      patients with Crohn's disease (CD) and a subset of their healthy relatives. A
      primary permeability defect was postulated in the pathogenesis of the disease.
      The aim of this study was to identify a possible genetic pattern in the
      distribution of CD and/or abnormal permeability. METHODS: Differential urinary
      excretion of lactulose and mannitol (L/ M) in complete CD families was
      determined. Controls included healthy families and families with ulcerative
      colitis. Pedigrees were used to compare the distribution of CD and/or increased
      permeability. RESULTS: The L/M was significantly increased in patients with CD.
      Seventeen of 67 first-degree relatives (25%) had a ratio greater than the upper
      limit (P95 = 0.0170). Permeability results of CD families showed a highly
      significant familial aggregation. The lack of a genetic pattern in relation with
      CD and occurrence of disturbed permeability especially within generation, points
      toward a shared environmental factor. Five of 14 healthy spouses (36%) of
      patients with CD had also an increased permeability, and prevalence of increased
      permeability was not higher in families with known familial occurrence (P =
      0.85). CONCLUSIONS: This large family study confirms an increased permeability in
      a subset of healthy relatives of patients with CD. However, the absence of a
      typical family pattern and the high prevalence in spouses is in favor of a common
      nongenetic factor or a subclinical disease manifestation.

PMID- 9287980
TI  - Combined analysis of randomized controlled trials of ursodeoxycholic acid in
      primary biliary cirrhosis.
AB  - BACKGROUND & AIMS: Long-term ursodeoxycholic acid (UDCA) therapy slows the
      progression of primary biliary cirrhosis. This study examined the effect of UDCA
      therapy on survival free of liver transplantation in a large group of patients.
      METHODS: Data from three clinical trials were combined in which patients with
      primary biliary cirrhosis were randomly assigned to receive UDCA (n = 273) or
      placebo (n = 275). After 2 years, patients from French and Canadian studies
      received UDCA for up to 2 years. Patients from the American study remained on
      their assigned treatment for up to 4 years. RESULTS: Survival free of liver
      transplantation was significantly improved in the patients treated with UDCA
      compared with the patients originally assigned to placebo (P < 0.001; relative
      risk, 1.9; 95% confidence interval, 1.3-2.8). Subgroup analyses showed that
      survival free of liver transplantation was significantly improved in medium- and
      high-risk groups (serum bilirubin level, 1.4 to 3.5 or > 3.5 mg/dL; P < 0.0001
      and P < 0.03, respectively) and histological stage IV subgroup (P < 0.01).
      CONCLUSIONS: Long-term UDCA therapy improves survival free of liver
      transplantation in patients with moderate or severe disease. An effect in
      patients with mild disease is probably not found because they do not progress to
      end-stage disease in 4 years.

PMID- 9287982
TI  - Relationship of necrosis to organ failure in severe acute pancreatitis.
AB  - BACKGROUND & AIMS: Pancreatic necrosis and organ failure are principal
      determinants of severity in acute pancreatitis. The purpose of this study was to
      determine the relationship of necrosis to organ failure in severe acute
      pancreatitis. METHODS: Patients with necrotizing pancreatitis from May 1992 to
      January 1996 were retrospectively studied. Pancreatic necrosis was identified by
      characteristic findings on dynamic contrast-enhanced computerized tomography scan
      and infected necrosis by computerized tomography-guided percutaneous aspiration.
      Organ dysfunction was defined in accordance with the Atlanta symposium. RESULTS:
      Organ failure was present in only 26 of 51 patients (51%). There was no
      difference in the prevalence of organ failure in infected necrosis compared with
      sterile necrosis (approximately 50% in both groups). Patients with increased
      amounts of necrosis did not have an increased prevalence of organ failure or
      infected necrosis compared with those with lesser amounts of necrosis. Patients
      with organ failure had an increased morbidity and mortality compared with those
      without organ failure. CONCLUSIONS: Organ failure occurred in only one half of
      patients with necrotizing pancreatitis. Because organ failure increases the
      severity of illness, studies of patients with necrotizing pancreatitis must
      stratify for organ failure to facilitate interpretation of results.

PMID- 9287985
TI  - Retinoic acid receptor beta regulates growth and differentiation in human
      pancreatic carcinoma cells.
AB  - BACKGROUND & AIMS: Retinoic acid receptor beta (RAR beta) expression is lost or
      decreased during malignant transformation in human pancreatic adenocarcinoma. The
      aim of this study was to evaluate the role of RAR beta expression in the
      propagation of a malignant phenotype in human pancreatic carcinoma cells.
      METHODS: Overexpression of RAR beta in the human pancreatic carcinoma cell line
      DAN-G was achieved by selecting stable transfected cell clones. Genomic
      integration and expression were verified by Southern and Northern blotting and
      electrophoretic mobility shift assays. Growth was determined by cell number and
      xenografts transplanted into nude mice. Differentiation was examined by
      immunohistochemistry. RESULTS: Overexpression of RAR beta in DAN-G cells
      inhibited cellular proliferation in vitro and in vivo. Furthermore, RAR beta
      overexpression resulted in induction of cellular differentiation in xenografted
      tumors as evidenced by increased tumor cell expression of duct cell
      differentiation markers carcinoembryonic antigen (CEA), CA19-9, and cytokeratin
      7. CONCLUSIONS: Decreased expression of RAR beta plays a key role in the
      maintenance of a malignant phenotype in human pancreatic adenocarcinoma and
      therefore represents a novel target for experimental strategies in the treatment
      of pancreatic cancer patients.

PMID- 9287983
TI  - Enhanced urokinase plasminogen activation in chronic pancreatitis suggests a role
      in its pathogenesis.
AB  - BACKGROUND & AIMS: Urokinase plasminogen activator (uPA) regulates plasmin
      generation from plasminogen. The aim of this study was to analyze the role of the
      plasminogen activator/plasmin system in chronic pancreatitis (CP). METHODS: Using
      Northern blot analysis, in situ hybridization, and immunohistochemistry, the
      expression of uPA, its receptor (uPAR), plasminogen activator inhibitor 1 (PAI
      1), and transforming growth factor beta 1 (TGF-beta 1) was studied in 14 patients
      undergoing pancreatic resection for CP. Normal control pancreatic tissue was
      obtained through an organ donor program. RESULTS: Eight of 14 CP samples showed
      concomitant increased expression (P < 0.001) of uPA (5.2-fold), uPAR (5.9-fold),
      and TGF-beta 1 (8.8-fold) messenger RNA (mRNA) compared with normal controls. PAI
      1 mRNA expression was increased (6.5-fold; P < 0.001) in all CP samples. By in
      situ hybridization, moderate to strong mRNA staining of all four factors was
      present in acinar cells, some ductal cells, and areas with ductal metaplasia in
      CP samples. A similar staining pattern was found by immunohistochemistry. Intense
      mRNA and immunostaining for all of these factors in CP samples was associated
      with a higher degree of pancreatic damage. CONCLUSIONS: uPA and its receptor may
      contribute to the lytic damage observed in CP by plasmin generation. Similarly,
      increased amounts of plasmin may activate latent TGF-beta, thereby leading to the
      accumulation of fibrotic tissue.

PMID- 9287981
TI  - Altered cardiovascular responsiveness to active tilting in nonalcoholic
      cirrhosis.
AB  - BACKGROUND & AIMS: The hyperdynamic circulation of cirrhosis has been related
      either to plasma volume expansion (increased preload) or peripheral arterial
      vasodilation (reduced afterload). The aim of this study was to evaluate
      cardiovascular function in patients with nonalcoholic cirrhosis by
      echocardiography. METHODS: Nineteen patients with abnormal sodium handling (11
      sodium excretors and 8 sodium retainers) and 15 healthy volunteers underwent
      echocardiographic evaluation of left ventricular end-diastolic volume index
      (LVEDVI) and left ventricular end-systolic volume index (LVESVI), left
      ventricular ejection fraction (LVEF), cardiac index (CI), mean arterial pressure,
      and systemic vascular resistance (SVR) during supine resting and after 5 minutes
      of standing. RESULTS: Supine patients had increased LVEF and CI and reduced
      LVESVI and SVR. LVEDVI was increased only in sodium excretors. Standing induced a
      decrease in LVEDVI in all subjects. Healthy volunteers maintained cardiovascular
      homeostasis by increasing LVEF and heart rate, whereas cirrhotic patients
      experienced a decrease in SVI and CI despite marked increments in heart rate,
      plasma renin activity, and plasma norepinephrine level. CONCLUSIONS: In patients
      with cirrhosis, the increased LVEF and reduced LVESVI while in a supine position
      point at reduced afterload as an important determinant of the hyperdynamic
      circulation. Evidence of an increased preload secondary to increased blood
      volume, indicated by a high LVEDVI and increased plasma atrial natriuretic
      peptide levels, was found only in sodium excretors. The altered response to
      active tilt in cirrhotic patients suggests an impaired myocardial contractility.

PMID- 9287984
TI  - The cystic fibrosis transmembrane conductance regulator as a marker of human
      pancreatic duct development.
AB  - BACKGROUND & AIMS: The cystic fibrosis transmembrane conductance regulator (CFTR)
      protein is a small conductance adenosine 3',5'-cyclic monophosphate (cAMP)
      activated chloride ion channel found in the apical membranes of epithelia within
      the pancreas, airway, intestine, bile duct, sweat gland, and male genital ducts.
      Pancreatic insufficiency is a feature of about 85% of patients with cystic
      fibrosis and is believed to be caused by pancreatic autolysis after pancreatic
      duct obstruction. The aim of this study was to investigate the expression of CFTR
      in the pancreas from early development to postnatal life to establish whether the
      CFTR plays a key role in development of the pancreatic duct epithelium. METHODS:
      Expression of CFTR from the start of the mid-trimester of human development
      through term to adult life by messenger RNA (mRNA) in situ hybridization was
      examined. RESULTS: CFTR mRNA is detected throughout the pancreatic duct
      epithelium and its pattern of expression follows the differentiation of the duct
      system. CONCLUSIONS: CFTR is a valuable marker of human pancreatic duct cell
      development and differentiation.

PMID- 9287986
TI  - Gallbladder relaxation in patients with pigment and cholesterol stones.
AB  - BACKGROUND & AIMS: Gallbladders with cholesterol stones show a defective
      contraction in response to agonists. The aim of this study was to investigate the
      muscle relaxation of human gallbladders with cholesterol or black pigment
      gallstones. METHODS: Gallbladder relaxation was measured in vitro using muscle
      strips and single muscle cells. Relaxation was expressed as percent inhibition of
      either basal active tension in strips or maximal cell contraction induced by
      diacylglycerol. The production of cyclic nucleotides was determined using a 125I
      labeled radioimmunoassay kit. RESULTS: Frequency-dependent relaxation evoked by
      electrical field stimulation was significantly lower in gallbladders with
      cholesterol stones than in gallbladders with pigment stones. Relaxation and
      adenosine 3',5'-cyclic monophosphate (cAMP) production induced by isoproterenol,
      vasoactive intestinal peptide, and forskolin were also significantly decreased in
      gallbladders with cholesterol stones. However, the relaxation in response to 8
      bromo-cAMP, nitric oxide (NO), and the NO donor S-nitroso-N-acetylpenicillamine
      (SNAP), which circumvent plasma membrane receptors and directly activate
      intracellular mechanisms, was similar in gallbladders with cholesterol and
      pigment stones. Guanosine 3',5'-cyclic monophosphate production induced by NO and
      SNAP was also similar. CONCLUSIONS: Human gallbladder muscle from specimens with
      cholesterol stones show an impaired relaxation and lower cAMP production compared
      with specimens with pigment stones. The muscle defect(s) responsible for this
      impairment seem to be in the plasma membranes.

PMID- 9287987
TI  - Hemodynamics of pancreatic ischemia in cardiogenic shock in pigs.
AB  - BACKGROUND & AIMS: Previous studies have shown that the renin-angiotensin axis
      plays a pivotal role in vasoconstriction of the gastric, intestinal, and hepatic
      circulations during cardiogenic shock. The aim of this study was to evaluate the
      fundamental hemodynamic mechanism of pancreatic ischemia during cardiogenic shock
      induced by pericardial tamponade. METHODS: Cardiogenic shock was induced by
      pericardial tamponade. Cardiac output (and total peripheral vascular resistance)
      was determined by thermodilution. Pancreatic blood flow (and vascular resistance)
      was determined with radiolabeled microspheres. RESULTS: Graded increases in
      pericardial pressure produced corresponding decreases in cardiac output to 42% +/
      1% and arterial pressure to 67% +/- 3% of baseline and increases in total
      peripheral vascular resistance to 146% +/- 5% of baseline. Pancreatic blood flow
      decreased disproportionately to 30% +/- 3% of baseline, because of a
      disproportionate increase in pancreatic vascular resistance to 220% +/- 19% of
      baseline. Previously confirmed blockade of the renin-angiotensin axis ablated
      this response, whereas confirmed blockade of the alpha-adrenergic system or
      vasopressin system had no significant effect. Without shock, central intravenous
      infusions of angiotensin II closely mimicked this selective vasoconstriction.
      CONCLUSIONS: Angiotensin-mediated selective pancreatic vasoconstriction results
      in significant pancreatic ischemia during cardiogenic shock.

PMID- 9287988
TI  - Induction of ferritin synthesis in ischemic-reperfused rat liver: analysis of the
      molecular mechanisms.
AB  - BACKGROUND & AIMS: Iron may catalyze the production of reactive oxygen species
      (ROS) during postischemic reoxygenation. Ferritin, a cellular iron storage
      protein, can either represent a source of iron or perform a cytoprotective action
      against ROS. The aim of this study was to address the role of ferritin in
      postischemic reperfusion. METHODS: Transcriptional and posttranscriptional
      mechanisms controlling ferritin gene expression were studied in reperfused rat
      livers. RESULTS: Proteolysis reduced ferritin levels 2 hours after reperfusion,
      but a concomitant increase of synthesis, accompanied by enhanced transcription
      and accumulation of H and L ferritin subunit messenger RNAs (mRNAs), almost re
      established normal ferritin content at 4 hours. Pretreatment with interleukin 1
      receptor antagonist (IL-1RA) did not prevent the rise of ferritin mRNAs. RNA
      bandshift assays showed that the activity of the iron regulatory proteins (IRPs),
      which control ferritin mRNA translation, declined early after reperfusion and
      recovered progressively thereafter. Pretreatment with either the antioxidant N
      acetyl cysteine or IL-1RA was sufficient to prevent almost completely down
      regulation of IRP activity. CONCLUSIONS: Postischemic reperfusion causes
      degradation of ferritin, possibly increasing iron levels. However, induction of
      ferritin gene transcription, possibly mediated by ferritin-derived iron and ROS
      mediated inactivation of IRP, which allows translation of ferritin mRNAs,
      counteracts this effect and concurs to reestablish the amount of ferritin, which
      may thus act to limit reperfusion damage.

PMID- 9287993
TI  - Evolution and current status of the Whipple procedure: an update for
      gastroenterologists.
AB  - The Whipple procedure has undergone a remarkable gradual evolution in the last 20
      years, of which many gastroenterologists are unaware. Improvements in staging,
      particularly staging laparoscopy with ultrasonography, have reduced the incidence
      of negative laparotomies. The forbidding mortality of pancreaticoduodenectomy,
      approximately 20% just a generation ago, has decreased precipitously in high
      volume referral centers. Near zero mortality rates are now common. Morbidity and
      length of stay have also been reduced. Cardiac and pulmonary complications have
      been markedly reduced, whereas others such as pancreatic fistula still remain a
      problem. Modifications of the procedure have been introduced to improve long-term
      outcome of pancreatic cancer and to lessen digestive sequelae. Total
      pancreatectomy and large regional excisions did not improve results. However, 5
      year survival rates of 20% are now reported by several centers for adenocarcinoma
      of the pancreas, and long-term survival rates for other periampullary tumors are
      approximately 40%. Pylorus-sparing procedures can be performed and may lessen
      postoperative sequelae. The clinical consequences of improved results are that
      large numbers of procedures are being performed at specialty centers, providing
      the opportunity to perform clinical trials, and that the procedure is used more
      widely, for instance, in benign diseases such as chronic pancreatitis.

PMID- 9287990
TI  - Recurrent familial prolonged intrahepatic cholestasis of pregnancy associated
      with chronic liver disease.
AB  - Four Puerto Rican sisters had recurrent prolonged cholestasis of pregnancy
      without preexisting or intercurrent hepatic disorders. Available information was
      reviewed on the course, mechanism, and sequelae of prolonged recurrent
      cholestasis after 14 pregnancies in the 4 sisters. Etiologic, clinical,
      laboratory, radiological, and morphological studies of the liver and biliary
      tract were assessed. Each sister had contraceptive pill-induced pruritus.
      Prolonged recurrent cholestasis in the eldest sister was followed by cirrhosis
      and death. The second and third sisters had biopsy evidence of portal triaditis
      and fibrosis after five and three pregnancies, respectively. Intrahepatic
      cholestatic cirrhosis was present after three pregnancies in the youngest sister,
      necessitating an orthotopic liver transplantation; a posttransplantation
      pregnancy was also associated with prolonged cholestasis. Recurrent prolonged
      intrahepatic cholestasis of pregnancy was followed by periportal fibrosis or
      cirrhosis in 4 sisters. This finding suggests that patients with prolonged
      cholestasis after pregnancy should be followed up for evidence of ongoing liver
      disease, should be counseled on the potential of recurrence and disease
      progression in future pregnancies, and should alert family members at risk of
      possible occurrence of the syndrome.

PMID- 9287991
TI  - Esophageal carcinosarcoma: a genetic analysis.
AB  - Carcinosarcoma of the esophagus is a rare malignant neoplasm that consists of
      both carcinomatous and sarcomatous elements. The histogenesis of the sarcomatous
      component is generally considered to result from metaplasia of carcinomatous
      cells toward mesenchymal differentiation. True carcinosarcoma, characterized as a
      collision between a carcinoma and a sarcoma, is extremely rare. We describe a
      patient with primary achalasia who developed a true carcinosarcoma of the
      esophagus in which clonal differences between carcinomatous and sarcomatous
      elements were genetically and immunohistochemically demonstrated. A polypoid
      tumor located in the middle third of the esophagus developed in a 51-year-old man
      with longstanding achalasia. The tumor was predominantly composed of spindle
      shaped sarcomatous cells. Squamous cell carcinoma in situ and islands of well
      differentiated squamous cell carcinoma in the sarcomatous element were
      histologically observed. The sarcomatous element was immunoreactive for both
      mesenchymal and myoid markers. The carcinomatous component expressed type I and
      type II cytokeratins as well as epithelial membrane antigen. Analysis for
      chromosomal loss of heterozygosity performed in multiple microdissected samples
      of each sarcomatous and carcinomatous element revealed distinct genetic
      clonalities. These differences in immunohistochemical and genetic clonalities
      suggest that the tumor composed of squamous cell carcinoma and leiomyosarcoma
      originated separately from epithelial and mesenchymal precursors.

PMID- 9287994
TI  - Diagnosis and management of hemochromatosis.

PMID- 9287995
TI  - Uroguanylin and guanylin: distinct but overlapping patterns of messenger RNA
      expression in mouse intestine.
AB  - BACKGROUND & AIMS: Uroguanylin and guanylin, endogenous ligands of the guanylate
      cyclase C receptor, are presumed to mediate fluid and electrolyte secretion in
      the intestine. The aim of this study was to characterize the expression patterns
      of uroguanylin and guanylin messenger RNA (mRNA) in the mouse intestine. METHODS:
      A mouse uroguanylin complementary DNA was amplified from a partial genomic clone,
      and Northern analyses and in situ hybridization were performed to localize
      guanylin and uroguanylin mRNA along the duodenal-colonic and crypt-villus axes.
      RESULTS: Uroguanylin mRNA was expressed throughout the mouse intestine and also
      in the kidney. Signal intensity was greatest in the small intestine for
      uroguanylin and in the distal small intestine and colon for guanylin. In situ
      hybridization showed uroguanylin mRNA localized predominantly in intestinal villi
      and the corticomedullary junction of the kidney, whereas guanylin mRNA was
      localized in both crypts and villi in the small intestine and to superficial
      epithelial cells in the colon. CONCLUSIONS: Mouse uroguanylin mRNA expression is
      discrete from guanylin expression in the intestine. The patterns of distribution
      in the intestine and the known pH optima of these ligands suggest a complementary
      role for these secretagogues.

PMID- 9287999
TI  - Medical progress and ulcer disease: three key observations that changed the
      compass.

PMID- 9287992
TI  - Acute hemoperitoneum after large-volume paracentesis.
AB  - Hemoperitoneum resulting from rupture of mesenteric varices is a rare
      complication of portal hypertension with a high mortality of up to 70%. This case
      report describes the symptoms, clinical course, and treatment of 4 patients with
      acute hemoperitoneum caused by mesenteric variceal bleeding after large-volume
      paracentesis. Abdominal pain and/or hemorrhagic shock developed in 4 patients
      (age, 48-68 years), admitted for refractory ascites, 3 hours to 4 days after 1-4
      large-volume paracenteses (> 4000 mL). Duplex sonography, performed in 3 of the 4
      patients before onset of bleeding, showed retrograde flow in the mesenteric
      veins, suggesting large-caliber mesenteric collateralization. Treatment consisted
      of surgical ligation followed by transjugular intrahepatic portosystemic shunt
      (TIPS) (2 patients) and emergency TIPS with embolization of the bleeding vessel
      (1 patient). One patient died before any intervention could be initiated. In
      these 4 patients, the concurrence of large-volume paracentesis and hemoperitoneum
      suggests their causal relationship. The mechanism may be a sudden reduction in
      intraperitoneal pressure increasing the pressure gradient across the wall of the
      mesenteric varices, resulting in rupture and bleeding. The awareness of this
      complication may accelerate the diagnostic process and treatment.

PMID- 9287998
TI  - The science of today is the clinical practice of tomorrow.

PMID- 9287996
TI  - Uroguanylin is expressed by enterochromaffin cells in the rat gastrointestinal
      tract.
AB  - BACKGROUND & AIMS: Guanylin and uroguanylin are recently discovered intestinal
      peptides. Identifying the type of cell that synthesizes and secretes each peptide
      is an important step toward defining their physiological functions. However, the
      site of uroguanylin expression has not been identified, and the site of guanylin
      expression remains controversial (some studies implicate goblet cells, whereas
      others implicate enterochromaffin cells). The aim of the present study was to
      identify cellular sites of uroguanylin expression in the rat gastrointestinal
      tract and resolve the guanylin localization controversy. METHODS: Polyclonal
      antibodies against two independent regions of the uroguanylin prohormone were
      raised and used to evaluate prouroguanylin expression by Western blotting and
      immunohistochemistry. In parallel, uroguanylin mRNA was localized by in situ
      hybridization. RESULTS: Uroguanylin propeptide expression is high in proximal
      small intestine, low in stomach and distal small intestine, and almost
      undetectable in large intestine. Uroguanylin-expressing cells are identified as a
      subpopulation of enterochromaffin cells. CONCLUSIONS: Previous results showing
      guanylin expression in enterochromaffin cells appear to be a consequence of
      antibody cross-reactivity for epitopes conserved between proguanylin and
      prouroguanylin. Expression of uroguanylin in enterochromaffin cells is consistent
      with the hypothesis that uroguanylin is secreted both apically (into the lumen)
      and basolaterally (into the circulation).

PMID- 9287997
TI  - Gastrin deficiency results in altered gastric differentiation and decreased
      colonic proliferation in mice.
AB  - BACKGROUND & AIMS: Gastrin is a peptide hormone important in the regulation of
      both acid secretion and differentiation of oxyntic mucosal cells of the stomach.
      To further elucidate the role of gastrin in the growth and development of the
      gastrointestinal tract, we have generated mice that are deficient in gastrin.
      METHODS: Gastrin-deficient mice were generated through targeted gene disruption.
      Gastric and colonic architecture were determined by routine histology and
      immunohistochemical techniques. Proliferation was assessed by 5-bromo-2'
      deoxyuridine incorporation. RESULTS: Targeted disruption of the gastrin gene
      resulted in mice incapable of expressing gastrin messenger RNA (mRNA) or
      producing gastrin peptide. This deficiency led to a marked change in gastric
      architecture, with a decrease in number of parietal and enterochromaffin-like
      cells and an increase in number of mucous neck cells. There was no difference in
      the proliferation labeling index of the stomach in gastrin-deficient mice (3.04%
      +/- 0.33%) compared with wild-type littermates (3.15% +/- 0.18%). The colon of
      gastrin-deficient mice seemed normal histologically, although there was a
      decreased proliferation labeling index (2.97% +/- 0.52%) compared with wild-type
      littermates (4.71% +/- 0.44%; P < 0.01). CONCLUSIONS: Gastrin is important in
      regulating the differentiation of the gastric mucosa and is a trophic factor for
      the colonic mucosa.

PMID- 9288000
TI  - Putting up a different front for food hypersensitivity.

PMID- 9288002
TI  - In search of a better aspirin: suppression of intestinal polyposis by targeted
      inhibition of cyclooxygenase 2.

PMID- 9288003
TI  - Of opie, opossums, and others: emergent ERCP for gallstone pancreatitis.

PMID- 9288004
TI  - A controlled trial of anti-tumor necrosis factor alpha antibody for Crohn's
      disease.

PMID- 9288001
TI  - Guanylin: where it's at! Why's it there?

PMID- 9287989
TI  - Regulation of endocytic-transcytotic pathways and bile secretion by
      phosphatidylinositol 3-kinase in rats.
AB  - BACKGROUND & AIMS: Phosphatidylinositol 3-kinases (PI3-K) are a family of enzymes
      that play key roles in control of cell growth, membrane recycling, and vesicular
      endoexocytotic processes. The aim of this study was to investigate the effect of
      a specific PI3-K inhibitor, wortmannin, on bile secretion, cytoskeleton
      organization, and endotranscytotic pathways in rats. METHODS: Isolated perfused
      rat liver (IPRL) and isolated rat hepatocyte couplets (IRHCs) were used. RESULTS:
      Wortmannin induced a 25% inhibition of basal bile flow in IPRL (P < 0.01).
      Horseradish peroxidase biliary excretion in the IPRL was markedly decreased by
      wortmanin. In IRHC incubated with 25 nmol/L wortmannin for 10 minutes at 37
      degrees C, morphological studies showed early significant dilatation of bite
      canalicular lumen (P < 0.001). At short intervals (3 minutes), uptake of the
      fluid-phase marker, Lucifer yellow, was markedly decreased by exposure to
      wortmannin (P < 0.001). At longer times (20 minutes), Lucifer yellow was retained
      in basolateral area of IRHC as compared with control cells, where the marker was
      rapidly transported to the pericanalicular area. In IRHC, wortmannin induced a
      marked disorganization of microfilaments. CONCLUSIONS: Wortmannin inhibits basal
      bile flow, endocytosis, and transcytotic transport of fluid-phase markers in the
      liver, and causes an early dilatation of the canalicular lumen and
      disorganization of microfilaments. These findings suggest that PI3-K is involved
      in the regulation of vesicle trafficking, cytoskeleton organization, and the
      process of bile formation.

PMID- 9288005
TI  - Colonoscopy versus barium enema: a reappraisal of the facts and issues.

PMID- 9288006
TI  - Bystander T-cell clones in chronic hepatitis C.

PMID- 9288010
TI  - Association of postprandial hypotension with incidence of falls, syncope,
      coronary events, stroke, and total mortality at 29-month follow-up in 499 older
      nursing home residents.
AB  - OBJECTIVE: To investigate whether a marked decrease in postprandial systolic
      blood pressure correlates with a higher incidence of falls, syncope, new coronary
      events, new stroke, and total mortality at long-term follow-up in older nursing
      home residents. DESIGN: In a prospective study of 499 nursing home residents aged
      62 years or older, at 29-month mean follow-up, the maximal reduction in
      postprandial systolic blood pressure was correlated with the incidence of falls,
      syncope, new coronary events, new stroke, and total mortality. SETTING: A large
      long-term health care facility. PATIENTS: The 499 ambulatory or wheelchair-bound
      residents included 354 women and 145 men, mean age 80 +/- 9 years (range 62-100).
      MEASUREMENTS AND MAIN RESULTS: The mean follow-up was 29 +/- 10 months (range 1
      36). At follow-up, falls had occurred in 199 persons (40%), syncope in 72 persons
      (14%), new coronary events in 139 persons (28%), new stroke in 61 persons (12%),
      and total mortality in 199 persons (40%). The mean maximal decrease in
      postprandial systolic blood pressure was 20 +/- 5 mm Hg for persons with falls
      and 12 +/- 4 mm Hg in persons without falls (P < 0.001); 23 +/- 5 mm Hg in
      persons with syncope and 14 +/- 5 mm Hg in persons without syncope (P < 0.001);
      18 +/- 6 mm Hg in persons with coronary events and 14 +/- 5 mm Hg in persons
      without coronary events (P < 0.001); 21 +/- 6 mm Hg in persons with stroke and 15
      +/- 5 mm Hg in persons without stroke (P < 0.001); and 17 +/- 6 mm Hg in persons
      who died and 15 +/- 5 mm Hg in persons who did not die (P < 0.001). Maximal
      decrease in postprandial systolic blood pressure was an independent risk factor
      for falls, syncope, new coronary events, new stroke, and total mortality. Age was
      an independent risk factor for new coronary events and for total mortality. Male
      sex was an independent risk factor for syncope, new coronary events, stroke, and
      total mortality. Prior falls was an independent risk factor for new falls. Prior
      syncope was an independent risk factor for new syncope. Prior stroke was an
      independent risk factor for new stroke. CONCLUSIONS: A marked reduction in
      postprandial systolic blood pressure in older nursing home residents was
      associated at long-term follow-up with a higher incidence of falls, syncope, new
      coronary events, new stroke, and total mortality.

PMID- 9288007
TI  - Childhood hepatocellular tumors in FAP.

PMID- 9288008
TI  - The value of hepatic iron index in cirrhosis.

PMID- 9288011
TI  - Criteria for enrolling dementia patients in hospice.
AB  - OBJECTIVE: Because survival time varies greatly, it is difficult for dementia
      patients to meet a key criterion for eligibility for the Medicare hospice
      benefit: a 6-month survival time. We have developed criteria for the Medicare
      hospice benefit that include the characteristics of advanced dementia and related
      medical complications. The purpose of the study was to determine survival time
      among dementia patients who met these criteria. Additionally, because the
      National Hospice Organization (NHO) developed its own guidelines while the study
      was in progress, we retrospectively examined the application of these guidelines
      to our sample. DESIGN: Two cohorts of hospice patients were studied
      longitudinally, each for 2 years. SETTING: Nine Midwestern hospice programs.
      PARTICIPANTS: Forty-seven patients were enrolled in home hospice and
      institutional hospice settings. MEASUREMENTS: Survival time consisted of the
      number of days between enrollment in the hospice program and death or the end of
      the study. Other measures included Activities of Daily Living, ratings of
      Appetite, Nourishment, and Mobility, Functional Assessment Staging (FAST), a
      Medical Complications Checklist, and a care plan concerning the use of
      medications for acute illness. RESULTS: Our hospice enrollment criteria predicted
      a median survival time of 4 months and a mean survival time of 6.9 months; 38% of
      patients survived for more than 6 months. FAST scores and Mobility ratings were
      significantly related to survival time. However, 41% could not be scored on the
      FAST as their disease progression was not ordinal. Among patients who could be
      scored on the FAST and who had reached Stage Seven C, their mean survival time
      was 3.2 months compared with 18 months among those who could be scored and had
      not reached this stage and 8.6 months among patients whose disease progression
      was not ordinal, P < .001. When the palliative care plans were examined, less
      aggressive care plans resulted in shorter survival times, P < .01. CONCLUSION:
      Our hospice enrollment criteria identified a group with a median survival time of
      4 months and a mean survival time of 6.9 months. Using NHO criteria relying on
      the FAST allows the identification of a subgroup with very high mortality and a
      short time until death. Although the FAST can identify a subgroup of appropriate
      candidates for hospice, sole reliance on this measure might decrease access to
      hospice care for many dementia patients.

PMID- 9288009
TI  - The process of care in preventive in-home comprehensive geriatric assessment.
AB  - OBJECTIVES: To describe the process of care of a program of in-home comprehensive
      geriatric assessment (CGA) and to determine: (1) if there are major findings in
      all domains of CGA (medical, functional, mental health, and social/
      environmental), (2) if there is a continued clinical yield when CGA is repeated
      annually, and (3) factors that affect patient adherence with recommendations from
      CGA. DESIGN: Descriptive prospective study of subjects allocated to the
      intervention group of a 3-year randomized trial of preventive in-home CGA.
      SETTING: Homes of participants living in an urban setting. PARTICIPANTS: Persons
      aged 75 years or older and living at home who received the intervention (N = 202
      subjects, mean age 80.8 years, 70% female, 95% white, 64% living alone).
      INTERVENTION: Annual in-home CGA and quarterly home visits by gerontologic nurse
      practitioners for 3 years. MEASUREMENTS: Detailed data were collected
      prospectively on clinical problems detected by CGA, and specific recommendations
      were made for these problems using an instrument developed explicitly for this
      project to study the CGA process. Subject adherence with these recommendations
      was also recorded. RESULTS: Major problems were identified in all domains of CGA;
      the most common problems were medical. In the first year, 76.7% of subjects had
      at least one major problem identified that was either previously unknown or
      suboptimally treated. One-third of subjects had additional major problems
      identified during the second and third years. A constant number of therapeutic
      and preventive recommendations was made each year (11.5 per subject annually).
      Subject adherence varied by type of recommendation (ANOVA, F = 108.4, P < .001);
      adherence was better for referrals to a physician than for referrals to a non
      physician professional or community service or for recommendations involving self
      care activities (Scheffe's test, P < .001). CONCLUSION: In these community
      dwelling older people, there was a continued yield of problems identified and
      recommendations made when CGA was repeated annually for 3 years, supporting the
      practice of repeat CGA in older people in the community. Subject adherence with
      recommendations from CGA varied by type of recommendation, but further work is
      needed to determine additional factors that affect this adherence and to
      determine the association between the yield of CGA (i.e., problems identified,
      recommendations given and adherence with these recommendations) and important
      clinical outcomes.

PMID- 9288013
TI  - Prospective evaluation of clinical criteria to select older persons with acute
      medical illness for care in a hypothetical home hospital.
AB  - OBJECTIVE: To evaluate criteria to select older persons who need hospitalization
      for common acute medical illnesses for care in a hypothetical home hospital.
      DESIGN: Prospective record review. SETTING AND PARTICIPANTS: Patients aged 65 and
      older admitted to the general medical service of a community-based university
      hospital. MEASUREMENTS: We developed illness-specific selection criteria to
      identify older persons with certain acute medical conditions for treatment in a
      hypothetical home hospital. The selection criteria were reviewed prospectively
      against all community-dwelling older patients admitted to the general medical
      service of a community-based university hospital over a 2-month period. We
      determined eligibility for home hospital admission based on information available
      at the time of admission and then tracked the patient's hospital course. RESULTS:
      One hundred fifty-seven admissions of 143 patients were reviewed. The selection
      criteria identified 33% of patients admitted to the acute hospital with one of
      the three target diagnoses as eligible for a home hospital model of care had it
      been available. Eligible patients experienced shorter lengths of stay (3.7 vs 5.4
      days, P = .012), fewer mean number of procedures performed (0.98 vs 1.70, P =
      .001), fewer mean number of complications (0.17 vs 0.56, P = .010), and fewer
      events that could be handled only in the acute hospital setting (P = .036). In
      addition, in logistic regression analysis, three criteria for home hospital
      ineligibility, pulmonary congestion associated with ischemic chest pain (odds
      ratio 6.85, 95% CI 2.64, 17.81), the presence of an acute coexisting illness
      requiring hospitalization independent of the target conditions (odds ratio 2.66,
      95% CI 1.11, 6.41), and significant pulmonary congestion after initial treatment
      (odds ratio 14.4, 95% CI 1.77, 117.41) were significantly associated with items
      difficult to accomplish at home. CONCLUSIONS: Criteria can be delineated that
      identify older persons with acute medical illnesses who may be suitable for
      treatment in a home hospital.

PMID- 9288017
TI  - To treat or not to treat: issues in decisions not to treat older persons with
      cognitive impairment, depression, and incontinence.
AB  - OBJECTIVES: To examine decisions not to treat problems identified during
      outpatient geriatric assessment, particularly problems of cognitive impairment,
      depression, or urinary incontinence. DESIGN: A descriptive study using patients'
      medical charts and survey data and interviews with clinical staff. SETTING: Four
      hospital-based, ambulatory, geriatric assessment clinics in Allegheny Country,
      PA. PARTICIPANTS: The sample comprised 128 older adults, recruited to a
      randomized, controlled clinical trial, who had problems associated with cognitive
      impairment, depression, or urinary incontinence. RESULTS: Although treatment was
      recommended for most of the problems relating to cognitive impairment,
      depression, and/or incontinence experienced by this group, slightly more than one
      third of cognitive impairment and depression problems and nearly one-half of
      incontinence did not receive treatment recommendations. Treatment rates varied
      considerably by condition and combination of comorbidity. Decisions not to treat
      are classified into six categories: patient or family refused treatment, the
      assessment was not completed, an intervention was already in place, concurrent
      problems or comorbities might have interfered with treatment, there was no
      documented diagnosis or there was a documented consideration and rule out of the
      problem, or no documented reason. CONCLUSION: Outpatient geriatric assessment
      units are designed to deal with the multiple problems experienced by their
      geriatric patients, and they identify successfully most problems presented by
      their frail constituents. However, identification of the patient's problems is
      only the first step in the assessment process and does not necessarily lead to
      either a documented diagnosis or to a treatment recommendation. Multiple social,
      cultural, environmental, and medical factors complicate the assessment process
      and, hence, the decision clinicians face when they decide whether to make
      recommendations to treat. These clinicians must weigh all medical and non-medical
      factors, including the patient's receptivity to treatment, when prioritizing the
      problems they deem to be treatable and making recommendations to treat.

PMID- 9288019
TI  - A survey of grief and bereavement in nursing homes: the importance of hospice
      grief and bereavement for the end-stage Alzheimer's disease patient and family.
AB  - OBJECTIVES: To determine the prevalence of grief and bereavement services in
      nursing homes. To highlight the importance of grief and bereavement as provided
      in the Medicare hospice benefit for the end-stage Alzheimer's Disease (AD)
      patient and family residing in long-term care facilities. DESIGN: Telephone
      survey of nursing homes. PARTICIPANTS: One hundred twenty-one nursing homes in
      the Lower Peninsula of the state of Michigan. MEASUREMENTS: The facilities were
      asked questions about on-site grief and bereavement services, services routinely
      offered by licensed hospice agencies. RESULTS: Fifty-five percent of the homes
      sent sympathy cards after the patients death. Ninety-nine percent of the
      facilities surveyed did not provide materials to the family or primary caregiver
      on the grieving process or bereavement after the death. None of the facilities
      sent a letter after the patients death informing them of local, community or on
      site bereavement support group meetings. Seventy-six percent of the homes were
      not able to offer a referral to a counseling or psychiatric professional when
      bereavement intervention was deemed appropriate. Fifty-four percent of the homes
      usually went to the funeral home or the funeral of a patient who died it their
      facility. Ninety-eight percent of the nursing homes neither visited, made phone
      calls, nor provided written communication (i.e., bereavement newsletter) to the
      family members after the patients death. CONCLUSION: The study demonstrated few
      grief and bereavement services for families of patients residing in long-term
      care facilities. Because grief and bereavement is part of the career of most
      Alzheimer's caregivers, access to the Medicare hospice benefit should be
      encouraged for families of patients with end-stage Alzheimer's Disease residing
      in nursing facilities.

PMID- 9288018
TI  - Advance planning for dementia caregivers.

PMID- 9288016
TI  - Everyday matters in the lives of nursing home residents: wish for and perception
      of choice and control.
AB  - OBJECTIVES: This study examined the importance that nursing home residents and
      nursing assistants ascribed to control and choice over everyday issues, the
      satisfaction of residents with their control and choice over these issues, and
      the nursing assistants' impressions of the extent to which control and choice
      exist for nursing home residents on everyday matters. DESIGN: Cross-sectional in
      person interviews with a stratified representative sample of nursing home
      residents and nursing assistants using semi-structured interview protocols with
      both fixed-choice and open-ended questions. SETTING: A random sample of 25
      nursing homes in the Twin Cities, MN area; a random sample of five nursing homes
      in North Little Rock, AR; all five nursing homes in Sante Fe, NM; and five
      purposively selected nursing homes in each of New York City and Los Angeles, CA.
      PARTICIPANTS: One hundred thirty-five cognitively intact residents, three from
      each facility, were selected and included the resident council chair, one
      randomly selected short-stay resident, and one randomly selected long-stay
      resident from each facility. Also participating were 134 nursing assistants (1
      selected randomly from each shift from those employed at least two-thirds time
      and who had worked in the facility for at least 3 months). MEASUREMENTS: The most
      important measurements were ordinal-level ratings of the importance of choice and
      control for nursing home residents over 10 selected areas of everyday life;
      ordinal measures of residents' satisfaction with their choice and control over
      these areas; and nursing assistants' ratings of the extent to which they thought
      it possible for residents to achieve choice and control. Open-ended comments were
      also elicited. Also measured were demographic data, ADL status, frequency of
      trips away from the nursing home, frequency of receiving visitors, and (for
      nursing assistants) length of employment, wages, job satisfaction, and extent to
      which they knew the residents under their care. MAJOR RESULTS: Cognitively intact
      nursing home residents attach importance to choice and control over matters such
      as bedtime, rising time, food, roommates, care routines, use of money, use of the
      telephone, trips out of the nursing home, and initiating contact with a
      physician. Nursing assistants view such control as important to residents.
      Residents and staff differ significantly in the importance attached to particular
      items, with staff placing lower importance than residents on use of the telephone
      and personal expenditures and higher importance on control and choice over
      visitors and formal nursing home activities. Residents were not very satisfied
      with their control and choice, and nursing assistants viewed them as unlikely to
      experience control and choice. Nursing home, resident, and staff characteristics
      were not associated with the patterns of results. CONCLUSIONS: A self-defeating
      cycle has been identified where neither resident nor staff are optimistic about
      achieving more resident control and choice, which both groups perceive as
      desirable. To end this cycle, suggestions are offered for structuring the role of
      the nursing assistant, physician and nurse leadership, changes in nursing home
      routines and practices, and public policy changes.

PMID- 9288015
TI  - Baseline correlates with quality of life among men and women with medication
      controlled hypertension. The trial of nonpharmacologic interventions in the
      elderly (TONE).
AB  - OBJECTIVES: To examine Quality of Life (QOL) and its correlates among older
      adults with medication-controlled hypertension. DESIGN: Baseline data from the
      TONE clinical trial. MEASUREMENTS: Demographic variables (age, race, income),
      hypertension treatment (medication class, years treated), health status (obesity,
      physical symptoms), and QOL status (MOS-Short-Form 36, Jenkins Sleep Disturbance,
      and CES-D Depression). PARTICIPANTS: A total of 975 men and women, aged 60 to 81
      years and free of major diseases and disability, with a screening blood pressure
      (BP) of < or = 145/85 mm Hg, treated medically for hypertension with
      antihypertensive medication. RESULTS: On average, TONE participants reported a
      QOL level on the SF-36 that was similar to or better than that reported by older
      adults in the general population. However, there was a strikingly high prevalence
      of physical complaints or symptoms: 90.3% of men and 93.3% of women experienced
      one or more physical symptoms or complaints, and nearly 50% reported that such
      symptoms had disrupted their daily functioning. Among variables-considered, only
      the physical symptoms index score, number of severe symptoms, and obesity status
      were correlated consistently with QOL among TONE men and women. Lower QOL scores
      were associated with higher symptom scores and with obesity. Neither medication
      class nor age were appreciably associated with QOL status. CONCLUSIONS: Physical
      symptoms, rather than medication class and age, were the strongest correlates of
      QOL in TONE. This underscores the importance of identifying the etiology of
      symptoms as a means to improve the QOL of order hypertensive persons rather than
      substituting medication. The association of poorer physical well-being with
      obesity suggests that weight reduction to manage BP may also improve QOL for some
      individuals.

PMID- 9288020
TI  - Circumstances of falls resulting in hip fractures among older people.
AB  - OBJECTIVES: To describe the circumstances of falls resulting in hip fractures
      among older people and to determine whether the circumstances differ by gender,
      age, and residential status. DESIGN: Cross-sectional study. SETTING: Two
      hospitals in Auckland, New Zealand, in which all individuals aged 60 years or
      older with a fracture of the proximal femur are hospitalized. PARTICIPANTS: A
      total of 911 individuals (97% response rate) were hospitalized with fractures of
      the proximal femur; 77% were women, 66% were aged 80 years or older, and 58% were
      living in private homes at the time of fracture. MEASUREMENTS: Data were
      collected face-to-face by a trained interviewer using a standardized
      questionnaire. RESULTS: Ninety-six percent of the fractures were associated with
      a fall, with fewer that 2% of subjects reporting that their fractures occurred
      spontaneously before a fall. Sixteen percent of fractures were associated with an
      acute medical or physical condition. Although 85% of the fractures involving a
      fall occurred at home, only about 25% of these were associated with an
      environmental hazard, and only a proportion of these were likely to have been
      amenable to modification. The circumstances of falls differed significantly by
      age and residential status. CONCLUSION: Strategies aimed at preventing fall
      related hip fractures among the old old and among institutionalized individuals
      should focus primarily on the modification of intrinsic factors. Modification of
      environmental hazards has the greatest potential for prevention among the young
      old and those living in private homes.

PMID- 9288012
TI  - Physician attitudes concerning warfarin for stroke prevention in atrial
      fibrillation: results of a survey of long-term care practitioners.
AB  - BACKGROUND: The prevalence of atrial fibrillation (AF) increases dramatically
      with advancing patient age, and, as a result, this condition is common in persons
      residing in the long-term care setting. OBJECTIVES: To assess the knowledge and
      attitudes of physicians regarding the use of warfarin for stroke prevention in
      patients with atrial fibrillation in long-term care facilities. METHODS: We
      surveyed physicians actively providing primary care to older patients in 30 long
      term care facilities located in New England, Quebec, and Ontario. Physicians were
      requested to complete a structured questionnaire about use of warfarin therapy
      for stroke prevention in patients with AF residing in long-term care facilities.
      The questionnaire included two clinical scenarios designed to provide substantial
      contrasts in patient characteristics including underlying comorbidity, functional
      status, bleeding risk, and stroke risk. RESULTS: A total of 269 physicians were
      asked to participate in the survey, and 182 (67.7%) completed the questionnaire
      between February 1, 1995, and July 31, 1995. Only 47% of respondents indicated
      that the benefits of warfarin therapy "greatly outweigh the risks" in this
      setting; the remainder of physicians indicated that benefits only "slightly
      outweigh the risks" (34%) or that risks "outweigh benefits" (19%). The most
      frequently cited contraindications to warfarin use were: excessive risk of falls
      (71%), history of gastrointestinal bleeding (71%), history of other non-central
      nervous system bleeding (36%), and history of cerebrovascular hemorrhage (25%).
      Among the 164 physicians who reported using the international normalized ratio to
      monitor warfarin therapy, 27% indicated a target range with a lower limit less
      than 2, 71% indicated a target range between 2 and 3, and 2% indicated an upper
      limit greater than 3. Among respondents who answered questions about the two
      clinical scenarios, estimates of the risk of a stroke without warfarin therapy
      and the risk of an intracranial hemorrhage with therapy varied widely.
      CONCLUSIONS: Our findings suggest that many uncertainties surround the decision
      to prescribe warfarin to patients with AF in the long-term care setting, as well
      as questions about the appropriate intensity of this treatment when it is
      prescribed. Concerns about the risks of bleeding appear to prevail over stroke
      prevention when physicians make such prescribing decisions.

PMID- 9288014
TI  - Psychotic symptoms and physically aggressive behavior in Alzheimer's disease.
AB  - OBJECTIVE: To examine the relationship between psychotic symptoms and subsequent
      physically aggressive behavior in outpatients with Alzheimer's disease. DESIGN:
      This observational study used a time series design to measure the presence and
      frequency of physically aggressive behavior over a 52-week period. Multiple
      regression models were used to evaluate delusions and hallucinations, assessed at
      baseline, as predictors of physical aggression, controlling for demographic and
      clinical variables. SETTING AND PARTICIPANTS: Of 315 consecutive eligible
      outpatients from the Rush Alzheimer's Disease Center, referred for evaluation for
      dementia, 270 (86%) participated in the study. All participants met NINCDS/ADRDA
      criteria for probable Alzheimer's disease; Mini-Mental State Examination scores
      ranged from 0 to 27, with a mean of 14.9 (SD = 5.6). MEASUREMENTS: Psychotic
      symptoms, previous episodes of physical aggression, and demographic variables
      were measured at baseline through a structured interview with an informant living
      in the same household. Physically aggressive behavior was measured sequentially
      at 1-week intervals over a period of 52 consecutive weeks and also through
      structured informant interviews. RESULTS: A total of 75 persons had one or more
      episodes of physical aggression during the 52 weeks of observation. The presence
      of delusions significantly predicted the presence and frequency of physical
      aggression. Of participants with high rates of physical aggression (> 1
      episode/month), 80% had delusions. This effect was robust, even after controlling
      for the effects of other clinical variables. By contrast, hallucinations did not
      reliably predict episodes of physical aggression. CONCLUSIONS: These data suggest
      that delusions, but not hallucinations, predict physically aggressive behavior in
      persons with Alzheimer's disease. In light of the persecutory nature of most
      delusional ideation in Alzheimer's disease, delusions may be associated with
      distortions in the perception of threat in common social situations.

PMID- 9288021
TI  - Use of the diagnosis "failure to thrive" in older veterans.
AB  - OBJECTIVES: To describe how physicians apply the term "failure to thrive" (FTT)
      to older patients. Specifically, to describe the clinical presentation,
      underlying etiologies, diagnostic and therapeutic interventions, and discharge
      outcomes of veterans having the discharge diagnosis of FTT. DESIGN: Retrospective
      chart review. SETTING: The Department of Veterans Affairs Medical Center (VAMC),
      Portland, Oregon, a 400-bed referral and teaching hospital. PARTICIPANTS: All
      veterans 65 years of age and older admitted to the Portland VAMC from October 1,
      1990, through September 30, 1993, whose coded discharge diagnoses included FTT (n
      = 132). MEASUREMENTS: Medical records were reviewed by a trained abstractor to
      obtain key data about clinical presentation, etiologies, interventions, and
      discharge outcomes. RESULTS: Subjects were predominantly male (98%), with a mean
      age of 76 years +/- 9 years. Weight loss was a key feature: 67% of subjects had
      evidence of weight loss by study criteria. Anemia was present in 55%, low
      cholesterol in 50%, and low albumin in 44%. Lymphopenia was common, present in
      66% of subjects. Most patients were admitted from home (83%); only 7% came from
      nursing homes. On admission, the majority (82%) were dependent in at least one
      ADL, and 36% were cognitively impaired. Cancer was the most common underlying
      diagnosis (30%), followed by infection (18%), dehydration (13%), and depression
      (12%). Only 46% of subjects were discharged home, while 34% went to nursing
      homes. Fourteen percent of subjects died during the hospitalization, an
      additional 11% died within 30 days after discharge, and 32% died within 1 year
      after discharge. The subgroup of subjects with cancer and/or infection had
      increased mortality rates at 30 days and 1 year after hospitalization.
      CONCLUSION: We conclude that FTT may constitute a discrete syndrome with
      diagnostic, therapeutic and prognostic implications in older people, but in the
      absence of consensus about diagnostic criteria, there is a large degree of
      subjective variation in how physicians apply the term.

PMID- 9288023
TI  - Is managed care good or bad for geriatric medicine?
AB  - This article uses clinical vignettes to examine the simultaneous dangers and
      opportunities that managed care brings to geriatric medicine. While the complex
      multifactorial syndromes prevalent in older adults might at first glance seem
      poorly handled under capitation, we argue that the incentives provided under
      existing delivery systems can be equally perverse. These improper incentives have
      arisen from (1) the fee-for-service payment mechanism itself, which has spawned a
      subspecialty culture ill-equipped to deal with the primary care needs of older
      adults and (2) the fragmentation of funding sources for geriatric care into two
      major payers (Medicare and Medicaid), encouraging providers to focus on cost
      shifting rather than the logical integration of services. The result has been a
      delivery system that provides little impetus to maximize functional status, the
      central goal of modern geriatric medicine. Because physicians may assume
      financial risk under global capitation, and because the cost of caring for a
      frail older adult is inversely related to functional status, managed care offers
      the potential to align the goals of cost containment with the goals of modern
      geriatric medicine. Physicians should have a substantive voice in the design and
      implementation of these systems.

PMID- 9288025
TI  - The history of geriatric medicine in Canada.

PMID- 9288022
TI  - Characteristics of patients receiving or foregoing resuscitation at the time of
      cardiopulmonary arrest.
AB  - OBJECTIVE: To compare clinical, functional and social characteristics of DNR
      patients at the time of their cardiopulmonary arrest with characteristics of
      patients who receive cardiopulmonary resuscitation. DESIGN: Retrospective chart
      review of all 261 patients who had a cardiopulmonary arrest during a 6-month
      period in an academic institution. SETTING: Teaching Veterans Affairs Medical
      Center serving a large metropolitan area. MEASUREMENTS: Demographic
      characteristics, medical diagnoses, and measures of functional status were
      collected when DNR orders were initiated and at the time of cardiopulmonary
      arrest. RESULTS: The mean age of the studied group was 62 years. Ninety-nine
      percent were males, and the majority were non-Hispanic white men. One hundred
      ninety-eight (76%) patients/proxies elected for limiting treatment. Most (85%)
      elected a DNR order only. Patients were the most frequently documented
      participants in advance directive decisions in the DNR group. At the time of
      cardiopulmonary arrest, a higher proportion of the CPR group had coronary artery
      disease or chronic renal failure, and a higher proportion of the DNR group had
      cancer or AIDS. The functional status of the DNR group deteriorated from the time
      of DNR order to death. At the time of cardiopulmonary arrest, the majority of
      both groups were dependent in all functional domains, and 70% of the DNR group
      were stuporous or comatose compared with 47% of the CPR group (P = .05). DNR
      patients were hospitalized for an average of 13.7 +/- 29.5 days after a DNR order
      was initiated. Six of the 81 patients who received CPR (7.4%) were alive at
      discharge. CONCLUSIONS: Patients and physicians deciding to implement a DNR order
      may be overly focused on medical diagnoses and less so on functional status. A
      significant proportion of patients with clinical characteristics associated with
      poor CPR outcome are electing for CPR.

PMID- 9288029
TI  - The state of geriatrics training programs: findings from the National Study of
      Internal Medicine Manpower (NASIMM) by Edward F. Lawlor, Christopher S. Lyttle,
      and Elisse Moldwin.

PMID- 9288028
TI  - Geriatrics in managed care: a call for papers.

PMID- 9288026
TI  - What does cell death have to do with aging?
AB  - When Lockshin and Zakeri discussed the relevance of apoptosis to aging 7 years
      ago, the common view was that apoptosis would have primarily a negative impact on
      aging by destroying essential and often irreplaceable cells. That view has now
      changed to one that acknowledges that there are two general ways in which
      apoptosis can play a role in aging: (1) elimination of damaged and presumably
      dysfunctional cells (e.g., fibroblasts, hepatocytes), which can then be replaced
      by cell proliferation, thereby maintaining homeostasis, and (2) elimination of
      essential post-mitotic cells (e.g., neurons, cardiac myocytes), which cannot be
      replaced, thereby leading to pathology. Evidence exists in two systems
      (fibroblasts and thymocytes/lymphocytes) that there are age-related decreases in
      the potential for apoptosis, although the molecular bases for the decreases in
      these two systems appear to differ. Upon becoming senescent, fibroblasts lose the
      ability to down-regulate expression of the bcl-2 gene in response to an apoptotic
      signal; thus, apoptosis is blocked even though an initiating signal has been
      received. In contrast, thymocytes/lymphocytes lack the ability to initiate the
      signal because of down-regulation of the cell surface receptor Fas. There is
      limited information available for other tissue types, and nothing is known about
      why and how age-related changes occur. An interesting observation is that the
      frequency of up-regulation of the bcl-2 gene as a result of chromosome
      translocation in otherwise normal B cells increases with age; the functional
      consequences of this phenomenon during aging are not known. The role of apoptosis
      in regulating cell number is also a promising area of research. The studies on
      liver damage and neoplastic lesions suggest an extremely important role for
      apoptosis in controlling cancer. This may be particularly important in the
      prostate where hypertrophy and/or cancer are a virtual certainty with ever
      increasing age. It is not known whether the ability to undergo apoptosis declines
      in the prostate with increasing age, but it appears possible that it may, thus
      explaining the loss of control over cell number in this tissue. A particularly
      important area of research is whether apoptosis plays a role in the changing
      balance between bone formation and resorption observed during osteoporosis.
      Monica Driscoll has already pointed out that, "regulation and execution of cell
      death is an absolutely critical process that interfaces with nearly every aspect
      of life. Future investigation of the links of cell death to cellular aging and
      the aging of organisms should be an exciting enterprise." The results currently
      available do suggest that apoptosis is a process that may be important in aging,
      at least in some tissues, and the mechanism of its regulation, in particular,
      needs to be understood. Several tumor suppressor gene and oncogene products are
      involved in signal transduction associated with apoptosis, but it remains to be
      shown which of these, if any, are actually involved in "on-off" switches for
      apoptosis. Where great progress has been made is in understanding the events
      occurring after binding of either Fas ligand or tumor necrosis factor to their
      respective receptors. However, one area about which little is known is the
      identity of the signals that initiate this process in response to intracellular
      damage. Through continuing research on cell death mechanisms, funded by the NIA,
      we hope to provide answers to such fundamental questions as: 1. Are there age
      related changes in apoptosis, and what role, if any, do these have in the aging
      process? 2. If age-related changes in apoptosis do occur, what molecular
      mechanisms are altered to produce these changes? 3. Can approaches be developed
      to improve the detection and elimination of damaged cells in vivo in tissues
      where cell replacement is possible? 4. Can death of damaged cells be attenuated
      or delayed in nonrenewable tissues, and, if so, is it advantageous to the org

PMID- 9288030
TI  - APOE4 testing for Alzheimer's disease.

PMID- 9288027
TI  - Hospice care for dementia patients.

PMID- 9288034
TI  - External hip protectors.

PMID- 9288032
TI  - Advance directives.

PMID- 9288033
TI  - Laparoscopic cholecystectomy in older Medicare patients.

PMID- 9288031
TI  - APOE4 genotyping.

PMID- 9288035
TI  - Subnormal serum vitamin B12 concentration.

PMID- 9288036
TI  - Quality control and essential drugs.

PMID- 9288038
TI  - MTHFR 677C-->T mutation, folate intake, neural-tube defect, and risk of
      cardiovascular disease.

PMID- 9288037
TI  - Treatment dilemma in childhood idiopathic thrombocytopenic purpura.

PMID- 9288024
TI  - The clinical diagnosis of heart failure in older patients.
AB  - OBJECTIVE: To review the differences in presentation and clinical manifestation
      of heart failure in older and younger patients and to determine if these
      differences influence the ability to diagnose the disorder clinically. Based on
      this information, an approach to diagnosing heart failure in older patients is
      provided. DATA SOURCE: Scientific reports regarding heart failure in both the
      general population and the geriatric population were identified from repeated
      searches of MEDLINE data base and citations from appropriate articles. DATA
      EXTRACTION AND SYNTHESIS: Relevant data were obtained from articles, with special
      importance placed on studies designed to examine older patients exclusively or as
      a subgroup in a larger study. Review of data pertaining to clinical
      characteristics and presentation of heart failure was performed, with emphasis on
      comparing the characteristics between age groups. Specific cardiac diseases that
      cause ventricular impairment in older patients were assessed, and the importance
      of systolic versus diastolic dysfunction in this age group was analyzed.
      CONCLUSION: Clinical diagnosis of heart failure in older patients may be
      difficult because of the absence of typical symptoms and physical findings. When
      present, the symptoms and signs may be mistakenly diagnosed as caused by
      concomitant disorders or aging changes. In other older patients, the symptoms and
      signs will be obscured by the presence of aging changes or the presence of other
      diseases. As a result of these difficulties, the initial diagnosis of heart
      failure in older patients is made later in the course of the cardiac disease
      process; older patients will be more unstable, and secondary preventive therapies
      may be of less benefit than in younger patients with the disorder. Though
      clinically difficult, the differentiation between systolic and diastolic
      ventricular dysfunction is mandatory in all older patients with heart failure.

PMID- 9288040
TI  - Are CS sprays safe?

PMID- 9288041
TI  - Physician empathy--should we care?

PMID- 9288039
TI  - Effects of systematic geriatric assessment.

PMID- 9288047
TI  - A running nose.

PMID- 9288043
TI  - Clinical value of 12-lead electrocardiogram after successful reperfusion therapy
      for acute myocardial infarction. Zwolle Myocardial infarction Study Group.
AB  - BACKGROUND: A simple clinical method to stratify risk for patients who have had
      successful reperfusion therapy after myocardial infarction is attractive since it
      facilitates the tailoring of therapy. METHODS: We investigated the clinical value
      of the 12-lead electrocardiogram (ECG), in 403 patients after successful
      reperfusion therapy by primary coronary angioplasty, in relation to infarct size
      measured by enzyme activity, left-ventricular function, and clinical outcome.
      ECGs were analysed to find the extent of the ST-segment-elevation resolution 1 h
      after reperfusion therapy. FINDINGS: A normalised ST segment was seen in 51% of
      patients, a partly normalised ST segment in 34%, and 15% had no ST-segment
      elevation resolution. Enzymatic infarct size and ejection fraction were related
      to the extent of the early resolution of the ST segment. The relative risk of
      death among patients with no resolution compared with patients with a normalised
      ST segment was 8.7 (95% CI 3.7-20.1), and that among patients with partial
      resolution compared with patients with a normalised ST segment was 3.6 (1.6-8.3).
      INTERPRETATION: Our findings suggest that ECG patterns reflect the effectiveness
      of myocardial reperfusion. Patients for whom reperfusion therapy by primary
      angioplasty was successful and who had normalised ST segments had limited damage
      to the myocardium and an excellent outlook during follow-up. Patients with
      persistent ST elevation after reperfusion therapy may need additional
      interventions since they have more extensive myocardial damage and have a higher
      mortality rate.

PMID- 9288045
TI  - Assessment of worldwide tuberculosis control. WHO Global Surveillance and
      Monitoring Project.
AB  - BACKGROUND: Because worldwide tuberculosis (TB) control had never been assessed,
      WHO set up a surveillance and monitoring project in 1995. The objectives were to
      assess the performance of national TB programmes; to assess the extent of
      implementation of the WHO strategy of TB control; and to attempt a comparison
      between regions that had adopted the WHO strategy and those that had not.
      METHODS: In June, 1996, we sent data-collection forms requesting information on
      national TB programmes' control policies, 1995 case notifications, and 1994
      treatment results to 216 countries, areas, and territories. We assessed the
      performance of national TB programmes by comparing case notifications with
      estimated incidence and by outcome of treatment in cohorts of patients. We also
      investigated worldwide treatment success and case detection among sputum-smear
      positive patients. FINDINGS: 180 (83%) of the 216 countries, areas, and
      territories surveyed replied to WHO (98% of the worldwide population). In 1995,
      the WHO control strategy had been implemented in 75 countries, and in 39 of these
      implementation was countrywide. UP to 23% of the worldwide population lived in
      regions where the strategy was available. In 1995, 3 297 688 cases of TB (all
      types) were reported, of which 1161411 (35%) were sputum-smear positive. 54% of
      all reported cases in countries that used the WHO strategy were sputum-smear
      positive, compared with 30% in other countries. The worldwide case-detection rate
      of new sputum-smear-positive cases was 35%. 92% of cases registered for treatment
      in 1994 in regions that used WHO strategy were assessed for outcome and 76% were
      treated successfully, compared with 54% and 42%, respectively, in regions that
      had not implemented the WHO strategy. Among cases reported worldwide in 1994, the
      documented treatment-success rate was 43%. INTERPRETATION: National TB programmes
      that have adopted the WHO TB control strategy achieve higher cure rates, but
      their impact on TB is modest on a worldwide scale. Wider continuous coverage with
      the WHO strategy is needed for effective worldwide TB control.

PMID- 9288044
TI  - Assessment of UK practice for management of acute childhood idiopathic
      thrombocytopenic purpura against published guidelines.
AB  - BACKGROUND: Guidelines for management of acute immune thrombocytopenic purpura
      (ITP) in childhood were published in 1992. Regional audit in 1995 showed
      substantial variation in clinical practice not related to clinical differences in
      patient groups, which indicated a need for national audit. METHODS: Individuals
      aged from birth to their 16th birthday newly presenting with ITP were identified
      over 14 months by regular mailing of paediatricians and haematologists for case
      notification. Information was obtained from follow-up by a detailed
      questionnaire. FINDINGS: ITP was clinically mild and benign in 323 (76%) of 427
      cases, including 181 (70%) of 260 cases with platelet counts below 10 x 10(9)/L.
      There were no deaths or intracranial haemorrhages. There was a substantial
      discrepancy between clinical practice and published guidelines: many children
      were admitted to hospital and received treatment unnecessarily; there was overuse
      of intravenous immunoglobulin (IVIg) as first-line therapy (94 children);
      children received steroids without marrow examination; and there was
      inappropriate use of platelet transfusions (41 with mild or moderate disease).
      INTERPRETATION: Our results indicate a need for change in practice.

PMID- 9288042
TI  - Systematic review of evidence on thrombolytic therapy for acute ischaemic stroke.
AB  - BACKGROUND: Recent trials of thrombolytic therapy in acute ischaemic stroke have
      given apparently conflicting results. Only one trial, the National Institute of
      Neurological Disorders and Stroke trial of tissue plasminogen activator (tPA),
      suggested that thrombolysis was definitely beneficial. To make sense of these
      results, we have done a systematic review of all available randomised trials of
      thrombolysis in acute ischaemic stroke. METHODS: From all available completed
      randomised trials of thrombolytic therapy compared with control in acute
      ischaemic stroke (with prerandomisation CT), we checked tabular data on deaths
      during roughly the first 2 weeks, deaths from all causes and functional outcome
      (disability) at the end of the trial follow-up period, and early symptomatic and
      fatal intracranial haemorrhages. FINDINGS: 12 trials included 3435 patients, of
      whom 694 (20%) were dead and 1001 (39%) of 2567 were functionally dependent at
      the end of follow-up (duration of follow-up varied between trials, but the
      longest was 6 months). 214 (6%) of the 3435 patients had early symptomatic or
      fatal intracranial haemorrhages. Thrombolytic therapy was associated with a
      significant excess of early deaths (91 per 1000 patients treated [95% CI 54
      134]), and total deaths (37 per 1000 [20-83]), but there was nevertheless a
      significant reduction in the number of patients in the combined outcome of dead
      or dependent (65 fewer per 1000 patients treated [28-107]). There was a
      substantial and significant excess of symptomatic and fatal intracranial
      haemorrhages with thrombolysis-which was similar in all recent trials-of about 70
      extra symptomatic intracranial haemorrhages per 1000 patients treated (of which
      51 per 1000 were fatal). In the cohort of patients randomised within 3 h of
      stroke, there was a significant reduction in the number of patients who were dead
      or dependent at the end of follow-up (141 fewer dead or dependent per 1000
      patients treated [75-206] and a non-significant increase in the number dead (nine
      per 1000 treated [-39 to 70]). There was significant heterogeneity between the
      trials for total deaths at the end of follow-up, which may be partly explained by
      differences in the use of antithrombotic drugs within the first 24 h of
      thrombolysis; the variation in severity of strokes included: the time window to
      thrombolytic treatment; and the dose of thrombolytic drug used. There were no
      direct comparisons of tPA with streptokinase or urokinase: much of the poor
      outcome in the streptokinase-treated patients might be explained by the inclusion
      of more severe strokes, greater use of antithrombotic drugs, higher doses, and
      the longer time to treatment compared with the trials that used tPA.
      INTERPRETATION: Thrombolysis requires further testing in large randomised trials
      because the risks seem substantial, and the benefit uncertain. The time window
      for effective treatment remains unclear. There is no objective evidence to
      suggest that tPA is safer than streptokinase; the apparent hazards and benefits
      may be similar when differences in trial design and baseline variables are
      accounted for.

PMID- 9288046
TI  - Association between polymorphism in gene for microsomal epoxide hydrolase and
      susceptibility to emphysema.
AB  - BACKGROUND: The first-pass metabolism of foreign compounds in the lung is an
      important protective mechanism against oxidative stress. We investigated whether
      polymorphisms in the gene for microsomal epoxide hydrolase (mEPHX), an enzyme
      involved in this protective process, had any bearing on individual susceptibility
      to the development of chronic obstructive pulmonary disease (COPD) and emphysema.
      METHODS: We designed PCR-based genotyping assays to detect variant forms of mEPHX
      that confer slow and fast activity. We used these assays to screen 203 blood
      donor controls and groups of patients with asthma (n = 57), lung cancer (n = 50),
      COPD (n = 68), and emphysema (n = 94), who were attending specialised clinics in
      Edinburgh, UK. FINDINGS: The proportion of individuals with innate slow mEPHX
      activity (homozygotes) was significantly higher in both the COPD group and the
      emphysema group than in the control group (COPD 13 [19%] vs control 13 [6%];
      emphysema 21 [22%] vs 13 [6%]). The odds ratios for homozygous slow activity
      versus all other phenotypes were 4.1 (95% CI 1.8-9.7) for COPD and 5.0 (2.3-10.9)
      for emphysema. INTERPRETATION: Genetic polymorphisms in xenobiotic enzymes may
      have a role in individual susceptibility to oxidant-related lung disease. Epoxide
      derivatives of cigarette-smoke components may be the cause of some of the lung
      damage characteristic of these diseases.

PMID- 9288049
TI  - Is there tissue penetration after application of topical salicylate formulations?

PMID- 9288048
TI  - Absence of viral rebound after treatment of HIV-infected patients with didanosine
      and hydroxycarbamide.

PMID- 9288050
TI  - Interaction between tramadol and phenprocoumon.

PMID- 9288051
TI  - Low medial prefrontal dopaminergic activity in autistic children.

PMID- 9288052
TI  - p53 mutations in BRCA1-associated familial breast cancer.

PMID- 9288053
TI  - Commuting, overtime, and cardiac autonomic activity in Tokyo.

PMID- 9288054
TI  - Mutations in GTP-cyclohydrolase I gene and vitiligo.

PMID- 9288055
TI  - Suppression of bladder hyperreflexia by intravesical resiniferatoxin.

PMID- 9288056
TI  - Endotoxin activity of collagenase and human islet transplantation.

PMID- 9288057
TI  - Who comes to be weighed: an exception to the inverse care law.

PMID- 9288058
TI  - Creutzfeldt-Jakob disease and eating squirrel brains.

PMID- 9288059
TI  - Havana. Assessing Cuba's approach to contain AIDS and HIV.

PMID- 9288061
TI  - Towards filmless and distance radiology.
AB  - To many people radiology is synonymous with films. For 20 years or so, however,
      it has been possible to capture digitally data traditionally displayed on film,
      and that was true from the beginning of computed tomography and magnetic
      resonance imaging too. There is more to picture archiving and communication
      systems (PACS) than the economies of filmlessness and the ability to modify
      images. To realise the full potential of PACS requires huge and expensively
      equipped networks linking the radiology department, hospital wards, outpatient
      clinics, laboratories, family doctors' clinics, and so on, permitting
      simultaneous consultations on different sites and almost instant reporting from
      specialist radiologists at a distance. The data sets that need to be transferred
      are huge but some of the technical obstacles are now being overcome and the past
      few years have seen some hospitals move to a filmless state. The more common
      pattern, though, will be a piecemeal approach. PACS and teleradiology certainly
      provide a quicker imaging service. How soon a total PACS will save money for a
      hospital operating budget is less clear.

PMID- 9288060
TI  - Cryptogenic fibrosing alveolitis.

PMID- 9288062
TI  - Tuberculosis: a clinical problem of international importance.

PMID- 9288063
TI  - Lisinopril and albumin excretion in diabetes.

PMID- 9288065
TI  - Lisinopril and albumin excretion in diabetes.

PMID- 9288064
TI  - Lisinopril and albumin excretion in diabetes.

PMID- 9288066
TI  - Lisinopril and albumin excretion in diabetes.

PMID- 9288067
TI  - Low-molecular-weight heparin and serum potassium.

PMID- 9288068
TI  - Folic acid and prevention of neural-tube defects.

PMID- 9288069
TI  - Folic acid and prevention of neural-tube defects.

PMID- 9288070
TI  - Folic acid and prevention of neural-tube defects.

PMID- 9288071
TI  - Trouble-shooting in minimally invasive direct coronary artery bypass.

PMID- 9288072
TI  - Directly observed therapy.

PMID- 9288073
TI  - Antioxidants and ischaemic heart disease.

PMID- 9288074
TI  - Antioxidants and ischaemic heart disease.

PMID- 9288075
TI  - Antioxidants and ischaemic heart disease.

PMID- 9288077
TI  - Medical ethics: the Israeli Medical Association.

PMID- 9288076
TI  - Codon 129 genotype and new variant CJD.

PMID- 9288078
TI  - Medical ethics: the Israeli Medical Association.

PMID- 9288079
TI  - Medical ethics: the Israeli Medical Association.

PMID- 9288080
TI  - Overdiagnosis of intestinal amoebosis in Turkey.

PMID- 9288081
TI  - UK country profile.

PMID- 9288082
TI  - Holes in the Swiss legislation?

PMID- 9288083
TI  - Save the males!

PMID- 9288084
TI  - From mighty mice to mighty cows.

PMID- 9288085
TI  - A tenascin knockout with a phenotype.

PMID- 9288086
TI  - Heterozygote advantage for HLA class-II type in hepatitis B virus infection.

PMID- 9288087
TI  - Imprinting of the Angelman syndrome gene, UBE3A, is restricted to brain.

PMID- 9288088
TI  - The Angelman syndrome candidate gene, UBE3A/E6-AP, is imprinted in brain.

PMID- 9288089
TI  - Stargardt's ABCR is localized to the disc membrane of retinal rod outer segments.

PMID- 9288090
TI  - What is expanded in progressive myoclonus epilepsy?

PMID- 9288091
TI  - Mutations in CDMP1 cause autosomal dominant brachydactyly type C.

PMID- 9288092
TI  - Ethics and genetics in China: an inside story.

PMID- 9288093
TI  - The use of a genetic map of biallelic markers in linkage studies.
AB  - Improvements in genetic mapping techniques have driven recent progress in human
      genetics. The use of single nucleotide polymorphisms (SNPs) as biallelic genetic
      markers offers the promise of rapid, highly automated genotyping. As maps of SNPs
      and the techniques for genotyping them are being developed, it is important to
      consider what properties such maps must have in order for them to be useful for
      linkage studies. I examine how polymorphic and densely spaced biallelic markers
      need to be for extraction of most of the inheritance information from human
      pedigrees, and compare maps of biallelics with today's genome-scanning sets of
      microsatellite markers. I conclude that a map of 700-900 moderately polymorphic
      biallelic markers is equivalent--and a map of 1,500-3,000 superior--to the
      current 300-400 microsatellite marker sets.

PMID- 9288094
TI  - A candidate gene for familial Mediterranean fever.
AB  - Familial Mediterranean fever (FMF) is an autosomal recessive disorder
      characterized by attacks of fever and serositis. In this paper, we define a
      minimal co-segregating region of 60 kb containing the FMF gene (MEFV) and
      identify four different transcript units within this region. One of these
      transcripts encodes a new protein (marenostrin) related to the ret-finger protein
      and to butyrophllin. Four conservative missense variations co-segregating with
      FMF have been found within the MEFV candidate gene in 85% of the carrier
      chromosomes. These variations, which cluster at the carboxy terminal domain of
      the protein, were not present in 308 control chromosomes, including 162 validated
      non-carriers. We therefore propose that the sequence alterations in the
      marenostrin protein are responsible for the FMF disease.

PMID- 9288095
TI  - DMBT1, a new member of the SRCR superfamily, on chromosome 10q25.3-26.1 is
      deleted in malignant brain tumours.
AB  - Loss of sequences from human chromosome 10q has been associated with the
      progression of human cancer. Medulloblastoma and glioblastoma multiforme are the
      most common malignant brain tumours in children and adults, respectively. In
      glioblastoma multiforme, the most aggressive form, 80% of the tumours show loss
      of 10q. We have used representational difference analysis to identify a
      homozygous deletion at 10q25.3-26.1 in a medulloblastoma cell line and have
      cloned a novel gene, DMBT1, spanning this deletion. DMBT1 shows homology to the
      scavenger receptor cysteine-rich (SRCR) superfamily. Intragenic homozygous
      deletions has been detected in 2/20 medulloblastomas and in 9/39 glioblastomas
      multiformes. Lack of DMBT1 expression has been demonstrated in 4/5 brain-tumour
      cell lines. We suggest that DMBT1 is a putative tumour-suppressor gene implicated
      in the carcinogenesis of medulloblastoma and glibolastoma multiforme.

PMID- 9288096
TI  - The early-onset torsion dystonia gene (DYT1) encodes an ATP-binding protein.
AB  - Early-onset torsion dystonia is a movement disorder, characterized by twisting
      muscle contractures, that begins in childhood. Symptoms are believed to result
      from altered neuronal communication in the basal ganglia. This study identifies
      the DYT1 gene on human chromosome 9q34 as being responsible for this dominant
      disease. Almost all cases of early-onset dystonia have a unique 3-bp deletion
      that appears to have arisen idependently in different ethnic populations. This
      deletion results in loss of one of a pair of glutamic-acid residues in a
      conserved region of a novel ATP-binding protein, termed torsinA. This protein has
      homologues in nematode, rat, mouse and humans, with some resemblance to the
      family of heat-shock proteins and Clp proteases.

PMID- 9288097
TI  - A mouse model for Zellweger syndrome.
AB  - The cerebro-hepato-renal syndrome of Zellweger is a fatal inherited disease
      caused by deficient import of peroxisomal matrix proteins. The pathogenic
      mechanisms leading to extreme hypotonia, severe mental retardation and early
      death are unknown. We generated a Zellweger animal model through inactivation of
      the murine Pxr1 gene (formally known as Pex5) that encodes the import receptor
      for most peroxisomal matrix proteins. Pxr1-/- mice lacked morphologically
      identifiable peroxisomes and exhibited the typical biochemical abnormalities of
      Zellweger patients. They displayed intrauterine growth retardation, were severely
      hypotonic at birth and died within 72 hours. Analysis of the neocortex revealed
      impaired neuronal migration and maturation and extensive apoptotic death of
      neurons.

PMID- 9288098
TI  - Disruption of human limb morphogenesis by a dominant negative mutation in CDMP1.
AB  - Chondrodysplasia Grebe type (CGT) is an autosomal recessive disorder
      characterized by severe limb shortening and dysmorphogenesis. We have identified
      a causative point mutation in the gene encoding the bone morphogenetic protein
      (BMP)-like molecule, cartilage-derived morphogenetic protein-1 (CDMP-1). The
      mutation substitutes a tyrosine for the first of seven highly conserved cysteine
      residues in the mature active domain of the protein. We demonstrate that the
      mutation results in a protein that is not secreted and is inactive in vitro. It
      produces a dominant negative effect by preventing the secretion of other, related
      BMP family members. We present evidence that this may occur through the formation
      of heterodimers. The mutation and its proposed mechanism of action provide the
      first human genetic indication that composite expression patterns of different
      BMPs dictate limb and digit morphogenesis.

PMID- 9288099
TI  - Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion.
AB  - The gene for spinocerebellar ataxia 7 (SCA7) has been mapped to chromosome 3p12
      13. By positional cloning, we have identified a new gene of unknown function
      containing a CAG repeat that is expanded in SCA7 patients. On mutated alleles,
      CAG repeat size is highly variable, ranging from 38 to 130 repeats, whereas on
      normal alleles it ranges from 7 to 17 repeats. Gonadal instability in SCA7 is
      greater than that observed in any of the seven known neuro-degenerative diseases
      caused by translated CAG repeat expansions, and is markedly associated with
      paternal transmissions. SCA7 is the first such disorder in which the degenerative
      process also affects the retina.

PMID- 9288100
TI  - A deletion in the bovine myostatin gene causes the double-muscled phenotype in
      cattle.
AB  - An exceptional muscle development commonly referred to as 'double-muscled' (Fig.
      1) has been seen in several cattle breeds and has attracted considerable
      attention from beef producers. Double-muscled animals are characterized by an
      increase in muscle mass of about 20%, due to general skeletal-muscle hyperplasia
      that is, an increase in the number of muscle fibers rather than in their
      individual diameter. Although the hereditary nature of the double-muscled
      condition was recognized early on, the precise mode of inheritance has remained
      controversial; monogenic (domainant and recessive), oligogenic and polygenic
      models have been proposed. In the Belgian Blue cattle breed (BBCB), segregation
      analysis performed both in experimental crosses and in the outbred population
      suggested an autosomal recessive inheritance. This was confirmed when the
      muscular hypertrophy (mh) locus was mapped 3.1 cM from microsatellite TGLA44 on
      the centromeric end of bovine chromosome 2 (ref. 5). We used a positional
      candidate approach to demonstrate that a mutation in bovine MSTN, which encodes
      myostatin, a member of the TGF beta superfamily, is responsible for the double
      muscled phenotype. We report an 11-bp deletion in the coding sequence for the
      bioactive carboxy-terminal domain of the protein causing the muscular hypertrophy
      observed in Belgian Blue cattle.

PMID- 9288101
TI  - Imprinted expression of the murine Angelman syndrome gene, Ube3a, in hippocampal
      and Purkinje neurons.
AB  - Angelman syndrome (AS) is a human genetic disorder characterized by mental
      retardation, seizures, inappropriate laughter, abnormal galt, tremor and ataxia.
      There is strong genetic evidence that the disorder is associated with a
      maternally expressed, imprinted gene mapping to chromosome 15q11-13. Affected
      patients demonstrate varied molecular abnormalities, including large maternal
      deletions, uniparental paternal disomy (UPD). Imprinting mutations and loss of
      function mutations of E6-associated-protein (E6-AP) ubiquitin-protein ligase
      (UBE3A). All of these abnormalities are associated with loss of maternal
      expression of UBE3A. Although mutations in UBE3A cause AS, indicating that
      maternal-specific expression of UBE3A is essential for a normal phenotype,
      evidence for maternal-specific expression of UBE3A has been lacking. Using mice
      with partial paternal UPD encompassing Ube3a to differentiate maternal and
      paternal expression, we found by in situ hybridization that expression of Ube3a
      in Purkinje cells, hippocampal neurons and mitral cells of the olfactory bulb in
      UPD mice was markedly reduced compared to non-UPD littermates. In contrast,
      expression of Ube3a in other regions of the brain was only moderately or not at
      all reduced in UPD mice. The major phenotypic features of AS correlate with the
      loss of maternal-specific expression of Ube3a in hippocampus and cerebellum as
      revealed in the mouse model.

PMID- 9288102
TI  - Familial colorectal cancer in Ashkenazim due to a hypermutable tract in APC.
AB  - Approximately 130,000 cases of colorectal cancer (CRC) are diagnosed in the
      United States each year, and about 15% of these have a hereditary component. Two
      well-defined syndromes, familial adenomatous polyposis (FAP) and hereditary non
      polyposis colorectal cancer (HNPCC), account for up to 5% of the total new cases
      of CRC. Truncating APC mutations are responsible for FAP, and defective mismatch
      repair genes cause HNPCC. However, the genes responsible for most of the familial
      cases are unknown. Here we report a mutation (T to A at APC nucleotide 3920)
      found in 6% of Ashkenazi Jews and about 28% of Ashkenazim with a family history
      of CRC. Rather than altering the function of the encoded protein, this mutation
      creates a small hypermutable region of the gene, indirectly causing cancer
      predisposition.

PMID- 9288103
TI  - Mapping of a familial essential tremor gene, FET1, to chromosome 3q13.
AB  - Essential tremor (ET), the most common movement disorder in humans, appears to be
      inherited as an autosomal dominant trait in many families. The familial form is
      called familial essential tremor (FET), which seems similar to sporadic essential
      tremor. ET is a cause of substantial disability, particularly in the elderly. The
      prevalence of Parkinson's disease and dystonia may be increased in families with
      ET, but other movement disorders are seldom encountered in these families. Here
      we report the results of a genome-wide scan for FET genes in 16 Icelandic
      families with 75 affected individuals, in whom FET was apparently inherited as a
      dominant trait. The scan, which was performed with a 10-cM framework map,
      revealed one locus on chromosome 3q13 to which FET mapped with a genome-wide
      significance when the data were analysed either parametrically, assuming an
      autosomal dominant model (lod score = 3.71), or non-parametrically (NPL Z score =
      4.70, p < 6.4 x 10(-6).

PMID- 9288105
TI  - Epilepsy and mental retardation limited to females: an X-linked dominant disorder
      with male sparing.
AB  - Several X-linked disorders affect females disproportionately or exclusively.
      These including focal dermal hypoplasia, oral-facial-digital syndrome type I
      (ref. 3) and epilepsy with bilateral periventricular heterotopias. X-linked
      dominant inheritance with male lethality is probably responsible for sex-limited
      expression of these disorders, as affected women have frequent spontaneous
      abortions and the sex ratio of their live offspring is often skewed. The same
      inheritance pattern has been proposed for Rett syndrome, Aicardi syndrome and
      microphthalmia with linear skin defects, but in these sporadic conditions,
      evidence of male lethality is lacking. We investigated an unusual family with
      epilepsy and mental retardation limited to females (EFMR, #121250 in ref. 9);
      this disorder is transmitted both by females and by completely unaffected carrier
      males. Assignment of the EFMR disease locus (EFMR) to the X chromosome indicates
      that selective involvement of females in X-linked disease may in some instances
      result from male sparing rather than male lethality.

PMID- 9288104
TI  - Secretory phospholipase Pla2g2a confers resistance to intestinal tumorigenesis.
AB  - Individuals inheriting the same mutation predisposing to cancer may show very
      different outcomes, ranging from early aggressive cancer to disease-free
      survival. Experimental mouse models can provide a powerful tool to identify
      factors in the environment and genetic background that account for such
      modifications. The Min mouse strain, in which the ApcMin mutation disrupts the
      mouse homologue of the human familial polyposis gene, develops intestinal
      neoplasms whose multiplicity is strongly affected by genetic background. We
      previously mapped a strong modifier locus, Mom1 (modifier of Min-1), to a 4-cM
      region on mouse chromosome 4 containing a candidate gene Pla2g2a encoding a
      secretory phospholipase. Here, we report that a cosmid transgene overexpressing
      Pla2g2a caused a reduction in tumour multiplicity and size, comparable to that
      conferred by a single copy of the resistance allele of Mom1. These results offer
      strong evidence that this secretory phospholipase can provide active tumour
      resistance. The association of Pla2g2a with Mom1 thus withstands a strong
      functional test and is likely to represent the successful identification of a
      polymorphic quantitative trait locus in mammals.

PMID- 9288106
TI  - Clustering of missense mutations in the ataxia-telangiectasia gene in a sporadic
      T-cell leukaemia.
AB  - Ataxia-telangiectasia (A-T) is a recessive multi-system disorder caused by
      mutations in the ATM gene at 11q22-q23 (ref. 3). The risk of cancer, especially
      lymphoid neoplasias, is substantially elevated in A-T patients and has long been
      associated with chromosomal instability. By analysing tumour DNA from patients
      with sporadic T-cell prolymphocytic leukaemia (T-PLL), a rare clonal malignancy
      with similarities to a mature T-cell leukaemia seen in A-T, we demonstrate a high
      frequency of ATM mutations in T-PLL. In marked contrast to the ATM mutation
      pattern in A-T, the most frequent nucleotide changes in this leukaemia were
      missense mutations. These clustered in the region corresponding to the kinase
      domain, which is highly conserved in ATM-related proteins in mouse, yeast and
      Drosophila. The resulting amino-acid substitutions are predicted to interfere
      with ATP binding or substrate recognition. Two of seventeen mutated T-PLL samples
      had a previously reported A-T allele. In contrast, no mutations were detected in
      the p53 gene, suggesting that this tumour suppressor is not frequently altered in
      this leukaemia. Occasional missense mutations in ATM were also found in tumour
      DNA from patients with B-cell non-Hodgkin's lymphomas (B-NHL) and a B-NHL cell
      line. The evidence of a significant proportion of loss-of-function mutations and
      a complete absence of the normal copy of ATM in the majority of mutated tumours
      establishes somatic inactivation of this gene in the pathogenesis of sporadic T
      PLL and suggests that ATM acts as a tumour suppressor. As constitutional DNA was
      not available, a putative hereditary predisposition to T-PLL will require further
      investigation.

PMID- 9288107
TI  - The Werner syndrome protein is a DNA helicase.
AB  - Werner syndrome (WS) is an uncommon autosomal recessive disorder characterized by
      premature aging. The clinical manifestations of WS, including atherosclerosis and
      osteoporosis, appear early in adulthood, and death in the fourth to sixth decade
      commonly ensues from myocardial infarction or cancer. In accord with the aging
      phenotype, cells from WS patients have a reduced replicative life span in
      culture. Genomic instability is observed at the cytogenetic level in the form of
      chromosome breaks and translocations and at the molecular level by multiple large
      deletions. The Werner syndrome gene (WRN) has recently been cloned. The predicted
      product is a 1,432-amino-acid protein whose central domain is homologous to
      members of the RecQ family of DNA helicases. Such homology does not necessarily
      mean that WRN encodes an active helicase. For example, the Saccharomyces
      cerevisiae RAD26 gene protein and the human transcription-repair coupling factor
      CSB (Cockayne syndrome 8) are highly homologous to known helicases, yet neither
      encodes an active helicase. Moreover, the Bloom's syndrome gene (BLM), discovered
      before WRN, is also homologous to the RecQ family of DNA helicases, though we
      still await demonstration that it encodes an active helicase. Here we report that
      the WS protein does indeed catalyze DNA unwinding.

PMID- 9288108
TI  - Tenascin-X deficiency is associated with Ehlers-Danlos syndrome.
AB  - The tenascins are a family of large extracellular matrix proteins with at least
      three members: tenascin-X (TNX), tenascin-C (TNC, or cytotactin) and tenascin-R
      (TN-R, or restrictin). Although the tenascins have been implicated in a number of
      important cellular processes, no function has been clearly established for any
      tenascin. We describe a new contiguous-gene syndrome, involving the CYP21B and
      TNX genes, that results in 21-hydroxylase deficiency and a connective-tissue
      disorder consisting of skin and joint hyperextensibility, vascular fragility and
      poor wound healing. The connective tissue findings are typical of the Ehlers
      Danlos syndrome (EDS). The abundant expression of TNX in connective tissues is
      consistent with a role in EDS, and our patient's skin fibroblasts do not
      synthesize TNX protein in vitro or in vivo. His paternal allele carries a novel
      deletion arising from recombination between TNX and its partial duplicate gene,
      XA, which precludes TNX synthesis. Absence of TNX mRNA and protein in the
      proband, mapping of the TNX gene and HLA typing of this family suggest recessive
      inheritance of TNX deficiency and connective-tissue disease. Although the precise
      role of TNX in the pathogenesis of EDS is uncertain, this patient's findings
      suggest a unique and essential role for TNX in connective-tissue structure and
      function.

PMID- 9288109
TI  - Fusion of retinoic acid receptor alpha to NuMA, the nuclear mitotic apparatus
      protein, by a variant translocation in acute promyelocytic leukaemia.
AB  - Acute promyelocytic leukaemia (APL) is uniquely associated with chromosomal
      translocations that disrupt the gene encoding the retinoic acid receptor, RARA.
      In more than 99% of cases, this disruption results in the formation of a PML-RARA
      gene fusion. Two rare variants of APL have been described, in which RARA is fused
      to one of two other genes, PLZF and NPM. Although RARA dysregulation is evidently
      important in APL, the role of the various fusion partners remains unclear. We
      have characterized a fourth APL gene fusion, which links exons encoding the
      retinoic acid and DNA-binding domains of RARA to 5' exons of NuMA, a gene that
      encodes the nuclear mitotic apparatus protein. The NuMA-RARA fusion protein
      exists in sheet-like nuclear aggregates with which normal NuMA partly co
      localizes. In contrast to t(15;17) APL, the intracellular distribution of PML is
      normal in these cells. Our results suggest that interference with retinoid
      signalling, and not disruption of PML organization, is essential to the APL
      phenotype and implicates for the first time an element of the mitotic apparatus
      in the molecular pathogenesis of human malignancy.

PMID- 9288111
TI  - Reverse genetics by chemical mutagenesis in Caenorhabditis elegans.
AB  - Traditional reverse genetics on yeast, mice and other organisms uses homologous
      recombination with transgenic DNA to interrupt a target gene. Here we report that
      target-selected gene inactivation can be be achieved in Caenorhabditis elegans
      with the use of chemical mutagens. We use PCR to selectively visualize deletions
      in genes of interest; the method is sensitive enough to permit detection of a
      single mutant among more than 15,000 wild types. A permanent frozen mutant
      collection of more than a million mutagenized animals has been established, and
      deletion mutants of several G-protein genes were isolated from it. The approach
      is suitable to be scaled up for systematic inactivation of all 17,000 C. elegans
      genes. Because it requires no transgenesis or cell culturing, it may also be
      applicable to small organisms usually considered to be outside the realm of
      reverse genetics (for example, other nematodes and insects). Any sequenced gene
      in any organism that can be handled in very large numbers can possibly be
      targeted in this way.

PMID- 9288110
TI  - Female embryonic lethality in mice nullizygous for both Msh2 and p53.
AB  - The mutator hypothesis of tumorigenesis suggests that loss of chromosomal
      stability or maintenance functions results in elevated mutation rates, leading to
      the accumulation of the numerous mutations required for multistep carcinogenesis.
      The human DNA mismatch repair (MMR) genes are highly conserved homologues of the
      Escherichia coli MutHLS system, which contribute to genomic stability by
      surveillance and repair of replication misincorporation errors and exogenous DNA
      damage. Mutations in one of these MMR genes, hMSH2, account for about half of all
      cases of genetically linked hereditary non-polyposis colorectal cancer. Loss of
      function of p53 has also been proposed to increase cellular hypermutability,
      thereby accelerating carcinogenesis, although a clear role for p53 in genomic
      instability remains controversial. p53 is mutated frequently in a wide range of
      human cancers, including colonic tumours. Both Msh2- and p53-targeted knockout
      mice are viable and susceptible to cancer. Here we demonstrate that combined Msh2
      and p53 ablation (Msh2-/-p53-/-) results in developmental arrest of all female
      embryos at 9.5 days. In contrast, male Msh2-/-p53-/- mice are viable, but succumb
      to tumours significantly earlier (t1-2 is 73 days) than either Msh2-/- or p53-/-
      littermates. Furthermore, the frequency of microsatellite instability (MSI) in
      tumours from Msh2-/-p53-/- mice is not significantly different than in Msh2-/-
      mice. Synergism in tumorigenesis and independent segregation of the MSI phenotype
      suggest that Msh2 and p53 are not genetically epistatic.

PMID- 9288112
TI  - Congenital hypothyroidism caused by a mutation in the Na+/l-symporter.

PMID- 9288113
TI  - A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in
      recessive Stargardt macular dystrophy.

PMID- 9288116
TI  - Activation of pp60c-src is necessary for human vascular smooth muscle cell
      migration.
AB  - BACKGROUND: The most widely distributed nonreceptor tyrosine kinase is pp60c-src
      (src), yet the role of this intracellular signaling protein in cell migration has
      not been defined. Given that smooth muscle cell (SMC) migration is essential for
      the development of intimal hyperplasia, we investigated the importance of src in
      locomotion of human vascular SMC. METHODS: SMC migration was evaluated using a
      microchemotaxis chamber assay and videomicroscopy. Src kinase activity was
      determined by measuring phosphorylation of a synthetic derivative of p34cdc2, a
      specific substrate for src. Blocking antibodies to src were introduced using a
      cytoplasmic microinjection technique. RESULTS: Stimulation of SMC with platelet
      derived growth factor (PDGF)-BB and AB resulted in an increase in src activation,
      whereas PDGF-AA did not consistently enhance src activity. These findings
      correlated with the ability of the PDGF isotypes to stimulate SMC chemotaxis;
      PDGF-BB and AB produced 7.4 +/- 0.3- and 5.3 +/- 0.5-fold increases in SMC
      chemotaxis, whereas PDGF-AA inhibited chemotaxis. SMC migration in response to
      PDGF-BB and serum was significantly inhibited by intracellular injection of a
      blocking antibody. CONCLUSIONS: Our findings reveal an association between
      agonist-induced src activation and chemotaxis. Moreover, an antibody that
      inhibits src activation dramatically inhibits migration of individual SMC. We
      conclude that activation of src is necessary for SMC migration. Because of its
      importance in SMC migration, either molecular or pharmacologic inhibitors of src
      may be useful in the control of intimal hyperplasia.

PMID- 9288115
TI  - CD28 blockade alters cytokine mRNA profiles in cardiac transplantation.
AB  - BACKGROUND: T-cell response to alloantigen is dependent on T-cell receptor
      activation and costimulation through the CD28 receptor, because T-cell receptor
      activation alone is insufficient for optimal immune response. The CD28 receptor
      on helper T cells interacts with its ligand B7 on activated B cells-macrophages
      as costimulus to support T-cell activity. CTLA4Ig is a recombinant inhibitor of
      CD28 receptor activation. In vivo studies with a rat major histocompatibility
      complex mismatch heterotopic cardiac transplant model demonstrate that CTLA4Ig
      prolongs cardiac allograft survival. This CTLA4Ig survival benefit is enhanced
      with prior donor-specific antigen exposure. METHODS: To investigate CTLA4Ig
      mechanisms, we examined the differential expression of B7 and cytokine mRNAs for
      interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-4, and IL-10 (Th1 or Th2
      activation) in cardiac allografts after treatment with CTLA4Ig and donor-specific
      antigen exposure versus conventional immunotherapy (cyclosporine,
      cyclophosphamide, or antilymphocyte serum). In the above major histocompatibility
      complex mismatch model, hearts (on day 5 after transplantation at peak rejection)
      had cytokine mRNA expression determined by semiquantitative reverse transcriptase
      polymerase chain reaction. RESULTS: Inhibition of B7 expression was observed in
      CTLA4Ig animals. Expression of IL-2 and IFN-gamma was near undetectable in
      CTLA4Ig and cyclophosphamide rats but was only moderately reduced by cyclosporine
      and antilymphocyte serum. IL-4 mRNA expression was reduced equally in all
      animals. Finally, IL-10 levels were unchanged by CTLA4Ig but were decreased by
      other therapies. CONCLUSIONS: The beneficial effect of CTLA4Ig, inhibiting
      expression of B7, alters Th1 cytokines IL-2 and IFN-gamma, with a resultant
      predominant IL-10 driven, Th2 tolerogenic response.

PMID- 9288117
TI  - Anti-interleukin-10 antibody restores burn-induced defects in T-cell function.
AB  - BACKGROUND: Studies have shown that susceptibility to sepsis after severe injury
      correlated with reduced production of T-helper 1 (Th1) cytokines (interleukin-2
      [IL-2] and interferon-gamma [IFN-gamma]) and a persistence of T-helper 2 (Th2)
      cytokines (IL-4 and IL-10). The mechanisms responsible for this effect are not
      clear. We used a T-dependent antigen to study both the effect of burn injury on
      antigen-specific Th functions in vivo and the effect of anti-IL-10 antibody on
      these functions. METHODS: Male A/J mice were anesthetized and given a 25% scald
      burn or a sham burn. On day 0 all mice were immunized with 100 micrograms
      trinitrobenzene sulfonic acid (TNP) haptenated ovalbumin (TNP-OVA) in complete
      Freund's adjuvant. Mice (10 per group) were given 250 micrograms monoclonal rat
      antimurine IL-10 antibody (anti-IL-10 MAB) or control rat immunoglobin G (IgG) on
      day 0 and 100 micrograms anti-IL-10 MAB or IgG on day 2. On day 10 the mice were
      killed to obtain serum and spleen cells. TNP-specific serum antibody isotype
      titers were determined by enzyme-linked immunosorbent assay (ELISA). Splenocyte
      proliferation and cytokine-production in response to TNP-OVA or to anti-CD3 MAB
      were determined by tritiated thymidine incorporation and by ELISA, respectively.
      RESULTS: Burn injury resulted in depressed levels of the TNP-specific IgG2a
      antibody isotype (Th1 dependent), whereas TNP-specific IgG1 and IgE (Th2
      dependent) levels were not decreased in burn versus sham burn mice. Anti-IL-10
      MAB but not IgG restored the IgG2a response. Burn injury also resulted in reduced
      TNP-OVA-specific proliferation of splenocytes, whereas anti-CD3 proliferation was
      equivalent in burn and sham mice. TNP-OVA-specific IL-2 and IFN-gamma production
      were significantly reduced by burn injury. Anti-IL-10 MAB restored TNP-OVA
      specific proliferation and antigen-specific IL-2 and interferon-gamma production
      by splenocytes from burn mice. CONCLUSIONS: Burn injury induces the loss of
      antigen-specific Th1 cell function, and IL-10 acts as a trigger to down-regulate
      Th1 activity after injury.

PMID- 9288118
TI  - Integrin regulation of polymorphonuclear leukocyte apoxis during hypoxia is
      primarily dependent on very late activation antigens 3 and 5.
AB  - BACKGROUND: Apoptosis is thought to be a central mechanism that leads to
      resolution of the inflammatory response. The regulation of polymorphonuclear
      leukocyte (PMN) apoptosis during hypoxia has not been previously characterized,
      and we hypothesized that integrin signaling by matrix proteins (laminin) would
      regulate PMN apoptosis. METHODS: PMNs at 1 x 10(5)/ml were adhered on plastic or
      laminin for 12 hours during normoxia or hypoxia. Apoptosis was determined both by
      cellular histologic evaluation and the TUNEL assays (Tdt). Phagocytosis in
      apoptotic PMNs was determined with two-color flow cytometric analyses with
      rhodamine-labeled heat-killed Escherichia coli (511 nm) and the Tdt reagent (563
      nm). Western blot analyses were performed on nine apoptotic regulatory proteins
      with monoclonal antibodies directed against each protein, and tyrosine
      phosphorylation was assessed after integrin receptor cross-linkage. RESULTS:
      Adherence of PMNs to laminin reduced apoptosis by cellular histologic evaluation
      and the Tdt method (%apoptosis = 19 +/- 1.0 versus 63 +/- 4.2 by histologic
      evaluation, 38 +/- 3.8 versus 60 +/- 10.5 by flow cytometry +/- adherence to
      laminin). Apoptosis-positive PMNs exhibited significantly greater phagocytosis
      than apoptosis-negative PMNs +/- laminin. Western blot analyses demonstrated
      increased p53 expression after 2 and 4 hours of hypoxia. Cross-linkage of very
      late activation antigen-3 (alpha 3/beta 1) resulted in the phosphorylation of 53
      kd, 44 kd, and 39 kd proteins at 30 seconds. CONCLUSIONS: (1) Chemotaxis of PMNs
      into the interstitium during hypoxia not only provides a means of ensuring PMN
      pathogen contact but also provides a mechanism for improved survival by reducing
      apoptosis. (2) The reduction of apoptosis is mediated primarily by very late
      activation antigen-3, which leads to a subsequent increase in the intracellular
      expression of p53 and increased bacterial phagocytosis.

PMID- 9288120
TI  - The natural resistance-associated macrophage protein gene is associated with
      Crohn's disease.
AB  - BACKGROUND: Identification of the genes causing inflammatory bowel disease (IBD)
      would enhance the understanding of and the treatment options for this disease. A
      hyperreactive immune response toward the intestinal flora has been implicated in
      the pathology of IBD. The natural resistance-associated macrophage protein
      (NRAMP) gene is believed to regulate macrophage function, especially the ability
      to fight intracellular pathogens. Genetic differences of NRAMP might, therefore,
      be associated with IBD. METHODS: Two DNA markers (D2S434 and D2S1323) near NRAMP
      were polymerase chain reaction (PCR) amplified and genotyped with DNA from 103
      patients with Crohn's disease, 85 patients with ulcerative colitis, and 98
      control subjects. Clinical data were obtained for all patients. Comparisons were
      made by chi-squared analysis. Disease association with significant haplotypes was
      expressed as odds ratio. RESULTS: Allele and genotype distributions were similar
      for both markers among all groups. Haplotype frequencies were different among
      Crohn's disease and control groups (p = 0.024). Two individual haplotypes of the
      patients with Crohn's disease were significant compared with control subjects: DA
      (p = 0.023; odds ratio, 0.5; 95% confidence interval, 0.3 to 0.9) and EA (p =
      0.001; odds ratio, 3.5; 95% confidence interval, 1.6 to 3.2). The haplotype
      distribution was different within three age-of-onset groups of patients with
      Crohn's disease (p = 0.05). CONCLUSIONS: This study is the first to report an
      association between the NRAMP gene and Crohn's disease.

PMID- 9288121
TI  - Src-mediated activation of the human neurotensin/neuromedin N promoter.
AB  - BACKGROUND: Expression of the gene encoding the neurotensin/neuromedin N (NT/N)
      is developmentally regulated in the gut in a distinctive temporal and spatial
      fashion. Src kinase, a nonreceptor tyrosine kinase, has been implicated in the
      growth and differentiation of various tissues; its role in gut differentiation is
      not known. The purpose of this study was to determine whether the Src signaling
      pathway plays a role in the activation of the human NT/N promoter. METHODS: Caco
      2 cells, a human colon cancer cell line that can differentiate to a small bowel
      phenotype, were transiently transfected with human NT/N promoter fragments linked
      to luciferase and various amounts of Src expression plasmids or dominant negative
      Raf; luciferase and beta-galactosidase activities were measured after 48 hours.
      RESULTS: Cotransfection of Src resulted in an approximate eightfold increase of
      NT/N promoter activity; mutation of a proximal activating protein-1/cyclic
      adenosine monophosphate responsive element site resulted in a dramatic decrease
      of Src-mediated NT/N induction. Cotransfection with a dominant negative Raf
      plasmid partially blocked Src-mediated NT/N activation. CONCLUSIONS: Src
      increases NT/N promoter activity in Caco-2 cells acting, in part, through a
      proximal AP-1/CRE promoter element. In addition, Src regulation of the NT/N
      promoter appears to be mediated through a Raf-dependent pathway. We propose that
      Src may play a role in tissue-specific gene expression in the gut.

PMID- 9288119
TI  - Impaired apoptotic death signaling in inflammatory lung neutrophils is associated
      with decreased expression of interleukin-1 beta converting enzyme family
      proteases (caspases).
AB  - BACKGROUND: Fas and tumor necrosis factor receptor 1 (TNFR1) are membrane
      proteins that signal for apoptotic cell death by downstream activation of
      proteins of the interleukin-1 beta converting enzyme (ICE) family. Spontaneous
      apoptosis is delayed in neutrophils activated by transmigration into an
      inflammatory focus. In this study we evaluated the effects of transmigration on
      Fas and TNFR1-induced apoptosis and apoptotic gene expression. METHODS: Sprague
      Dawley rats were killed 4 hours after intratracheal challenge with 500 micrograms
      lipopolysaccharide (LPS). Neutrophils isolated from the systemic circulation
      (circulation) or bronchoalveolar lavage fluid (lung) were incubated with or
      without an agonistic antibody to Fas (clone CH-11, 100 ng/ml) or TNF (10 ng/ml)
      for 24 hours. Apoptosis and Fas expression were assessed by flow cytometry.
      Expression of the antiapoptotic protein Bcl-2 and proapoptotic proteins ICE and
      CPP32 were measured by Western blots. RESULTS: Neutrophils transmigrating into
      the lung in response to LPS showed delayed apoptosis compared with circulating
      neutrophils and failed to undergo apoptosis in response to anti-Fas antibody or
      TNF-alpha. Fas expression was unaltered; however, TNFR1 expression was reduced.
      Bcl-2 was not detected in either group; both the pro- and active forms of ICE and
      active CPP32 were significantly decreased in lung neutrophils. The specific ICE
      inhibitor, YVAD-CMK, partially blocked the increased rates of apoptosis resulting
      from engagement of Fas or TNFR1. CONCLUSIONS: Neutrophil transmigration retards
      apoptosis through engagement of the death receptors Fas and TNFR1. This
      refractory state is associated with reduced levels of proapoptotic proteins.
      Blunted responsiveness to physiologic apoptotic stimuli prolongs neutrophil
      functional survival during acute inflammation and may contribute to the tissue
      injury associated with acute respiratory distress syndrome.

PMID- 9288122
TI  - Cyclin-dependent kinase inhibitors block proliferation of human gastric cancer
      cells.
AB  - BACKGROUND: Olomoucine and roscovitine are novel compounds that are designed to
      inhibit cyclin-dependent kinases (e.g., Cdk2 and cdc2). Cdks regulate progression
      through key checkpoints of the cell cycle. The purpose of this study was to
      determine (1) whether olomoucine and roscovitine inhibit Cdk2 and cdc2 kinase
      activities of the human gastric cancer cell line SIIA and (2) whether olomoucine
      and roscovitine block cell proliferation and cell cycle progression. METHODS:
      SIIA cells were treated with olomoucine or roscovitine and examined for Cdk2 and
      cdc2 activities by using histone H1 as the substrate. Cell numbers were counted
      with a Coulter counter. Cell cycle distribution was analyzed by DNA flow
      cytometry. RESULTS: Olomoucine and roscovitine completely blocked Cdk2 and cdc2
      activities in SIIA cells. Both compounds were also able to inhibit proliferation
      of SIIA cells, as well as three other human gastric cancer cell lines (AGS, MKN45
      630, and SNU-1). Cell cycle analysis showed that treatment with olomoucine or
      roscovitine for 24 hours led to a decrease in the S phase population and an
      increase in the G2/M population. CONCLUSIONS: We have shown that Cdk inhibitors,
      olomoucine and roscovitine, are a new class of antineoplastic molecules with
      potential therapeutic benefits for gastric cancers.

PMID- 9288123
TI  - Nitric oxide attenuates platelet-activating factor priming for elastase release
      in human neutrophils via a cyclic guanosine monophosphate-dependent pathway.
AB  - BACKGROUND: Nitric oxide (NO) has proven benefits in treating adult respiratory
      distress syndrome (ARDS). The protective mechanism remains unclear, but cyclic
      guanosine monophosphate (cGMP)-dependent signal transduction pathways have been
      suggested. Our laboratory has implicated polymorphonuclear neutrophil (PMN)
      priming and subsequent activation in the pathogenesis of postinjury ARDS and has
      shown that NO inhibits superoxide anion production from activated PMNs. More
      recently, the pivotal role of elastase in PMN-mediated tissue injury has been
      emphasized. Consequently, our study hypothesis was that NO attenuates platelet
      activating factor (PAF) priming for elastase release through a cGMP-dependent
      pathway in human PMNs. METHODS: PMNs isolated from human volunteers were
      preincubated with the NO donor 3-morpholinosydnonimine hydrochloride (SIN-1; 10(
      6) to 10(-2) mol/L), cGMP (10(-3) mol/L), or the cell-permeable cGMP analog
      dibutyryl-cGMP (10(-3) mol/L) for 10 minutes. The cells were then primed with
      platelet-activating factor (PAF) 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine
      (200 nmol/L), which was followed by N-formyl-methionyl-leucyl-phenylalanine
      (fMLP) activation (1 mumol/L). Elastase release was measured by the cleavage of N
      methoxysuccinyl-Ala-Ala-Pro-Val p-nitroanilide (AAPV-pNA). RESULTS: NO (through
      SIN-1) significantly attenuated elastase release from PAF-primed PMNs in a dose
      dependent manner. Cell-permeable dibutyryl-cGMP attenuated PMN elastase release
      similar to NO, but cGMP (not cell-permeable) had no effect. CONCLUSIONS: NO
      attenuates elastase release from PAF-primed PMNs through an intracellular cGMP
      dependent signal transduction pathway. These findings may partially explain the
      beneficial effects of NO in the treatment of postinjury ARDS and add to our
      knowledge of the complex intracellular pathways involved in NO/PMN interactions.

PMID- 9288124
TI  - Protein kinase C regulates macrophage tumor necrosis factor secretion: direct
      protein kinase C activation restores tumor necrosis factor production in
      endotoxin tolerance.
AB  - BACKGROUND: Macrophages pretreated in vitro with endotoxin (LPSp) secrete less
      tumor necrosis factor (TNF) in response to a second LPS activating (LPSa)
      stimulus. Protein kinase C (PKC) is required for TNF secretion in a macrophage
      stimulated with LPSa. In these experiments we examined the role of PKC in TNF
      signal transduction in naive and tolerant macrophages. METHODS: Murine
      macrophages were cultured +/- LPSp for 24 hours. Cultures were washed and treated
      for 1 hour with PKC inhibitors or phorbol myristate acetate (PMA), a direct PKC
      activator. Cells were then stimulated with a range of LPSa for 6 hours, and TNF
      was determined by bioassay. RESULTS: LPSa-stimulated TNF secretion by nontolerant
      macrophages was inhibited by LPSp in the absence of PMA. PKC inhibitors decreased
      TNF by naive macrophages and exaggerated inhibition in tolerant cells. Depletion
      of PKC by 24 hours of PMA decreased TNF production by both naive and tolerant
      macrophages. PKC activation with PMA 1 hour before LPSa augmented TNF secretion
      in naive cells and reversed TNF inhibition of tolerant cells. CONCLUSIONS: Direct
      PKC activation with PMA restored TNF secretion in LPS-tolerant macrophages.
      Endotoxin tolerance may alter the LPSa signal transduction pathway between the
      LPS receptor and PKC activation.

PMID- 9288125
TI  - Tolerance to heart and kidney grafts induced by nondepleting anti-CD4 monoclonal
      antibody (RIB 5/2) versus depleting anti-CD4 monoclonal antibody (OX-38) with
      donor antigen administration.
AB  - BACKGROUND: The monoclonal antirat CD4 antibody RIB 5/2 has been shown to
      modulate the CD4 glycoprotein without eliminating the affected T cells. We have
      shown that the administration of multiple doses of RIB 5/2 during the
      peritransplantation period prevents the rejection of rat kidney allografts.
      METHODS: We compared the efficacy of a single intraperitoneal dose of 20 mg/kg
      RIB 5/2 plus donor antigen (25 x 10(6) spleen cells [SCs]) given by either an
      intrathymic or an intravenous route with the depleting anti-CD4 monoclonal
      antibody (mAb) OX-38 plus antigen 21 days before a major histocompatibility
      complex (MHC)-mismatched Lewis (RT1l) to Buffalo (RT1b) rat cardiac or renal
      allograft. By delaying the transplantation for 21 days, recovery from the
      nonspecific effects of the antibody treatment allowed the demonstration of donor
      antigen-specific tolerance. RESULTS: OX-38 mAb given with intrathymic SCs induced
      tolerance to heart but not kidney grafts, whereas OX-38 given with intravenous
      SCs failed to prolong survival of either heart or renal allografts. In contrast,
      RIB 5/2 mAb administration, when combined with alloantigen given by either
      intravenous or intrathymic routes, induced tolerance to heart allografts, whereas
      only alloantigen given by the intravenous route with RIB 5/2 resulted in
      tolerance to renal grafts. CONCLUSIONS: Concomitant administration of intravenous
      donor alloantigen and the modulation of CD4+ recipIent cells by nondepleting RIB
      5/2, rather than elimination of these CD4+ cells with depleting mAb OX-38, is a
      more potent method for the induction of allograft tolerance.

PMID- 9288126
TI  - In vivo depletion of host CD4+ and CD8+ cells permits engraftment of bone marrow
      stem cells and tolerance induction with minimal conditioning.
AB  - BACKGROUND: Solid organ transplantation has become the preferred approach for the
      treatment of end-stage organ failure. However, the toxicity associated with the
      nonspecific immunosuppression essential to graft survival is substantial. Bone
      marrow transplantation (BMT) can overcome these limitations by the induction of
      donor-specific tolerance. The morbidity and mortality associated with fully
      ablative conditioning used to achieve engraftment has prevented the clinical
      application of BMT for induction of tolerance for solid organ transplantation.
      Although it was previously believed that fully ablative conditioning was
      essential to achieve engraftment, it has recently become apparent that partial
      conditioning may be sufficient to achieve chimerism and tolerance. The focus of
      this study was to characterize which cells in the host microenvironment must be
      eliminated for engraftment of MHC-disparate bone marrow to be achieved. METHODS:
      C57BL/10SnJ mice were depleted of CD4+, CD8+, or both cell types with monoclonal
      antibodies before irradiation with 300 centigray (cGy) and transplantation of 15
      x 10(6) allogeneic (B10.BR) bone marrow cells. Two days after transplantation the
      animals were treated with 200 mg/kg cyclophosphamide. Animals were typed for
      chimerism at 28 days and monthly thereafter. RESULTS: The combination of CD4+ and
      CD8+ depletion resulted in multilineage engraftment in 76.5% of the animals at a
      level of 57.1 +/- 17.7%. The depletion of CD4+ cells alone was not sufficient to
      allow engraftment, whereas depletion of CD8+ cells alone was. CONCLUSIONS: T
      cells in the recipient's marrow space play an important role in hindering
      allogeneic engraftment in the mouse. The T-cell subset responsible appears to be
      CD8+ cells rather than CD4+ cells.

PMID- 9288127
TI  - Active immunization using dendritic cells mixed with tumor cells inhibits the
      growth of primary breast cancer.
AB  - BACKGROUND: Dendritic cells (DCs) are potent antigen-presenting cells regarded as
      crucial in the priming of an immune response. The goal of our study was to test
      whether bone marrow-generated DCs are capable of inducing protective immunity
      against a murine breast carcinoma (4T1). METHODS: DCs were grown from Balb/c mice
      by culturing lymphocyte-immunodepleted bone marrow in murine granulocyte
      macrophage colony-stimulating factor containing medium for 10 days. Balb/c mice
      (five to eight per group) were immunized intradermally with 1 x 10(6) DCs mixed
      with 2 x 10(6) lethally irradiated 4T1 cells on day 0. Mice in control groups
      were given intradermal inoculations of phosphate-buffered saline solution, 1 x
      10(6) DCs, or lethally irradiated 4T1 cells alone. Booster intraperitoneal
      immunizations of 2 x 10(6) lethally irradiated 4T1 cells were given on days 7 and
      14. All mice were challenged with 5 x 10(3) 4T1 cells subcutaneously 7 days after
      the final immunization. Animals were examined daily, and tumor volume was
      recorded twice weekly with calipers. RESULTS: At 21 days there was a significant
      reduction in tumor growth in mice immunized with DCs mixed with irradiated 4T1
      cells as compared with the control groups (p = 0.0005, Kruskal-Wallis test).
      CONCLUSIONS: These results suggest that DCs mixed with tumor cells as a source of
      undefined tumor antigen can induce an effective antitumor immune response. This
      finding provides a rationale for the use of cultured DCs in immunotherapy of
      breast and other cancers.

PMID- 9288128
TI  - Generation of peptide-specific cytotoxic T lymphocytes using allogeneic dendritic
      cells capable of lysing human pancreatic cancer cells.
AB  - BACKGROUND: Dendritic cells (DCs) are potent antigen presenting cells (APCs),
      able to efficiently induce primary T cell-mediated responses to foreign antigens.
      In earlier studies we were able to identify a histocompatibility antigen (HLA)-A
      2-restricted nine amino acid peptide (GP2, peptide 654-662) from the
      transmembrane portion of the protooncogene HER2/neu as a tumor-associated antigen
      (TAA) in human pancreatic cancer. METHODS: Peripheral blood mononuclear cells
      (PBMCs) of HLA-A2+ and HLA-A2 healthy volunteers were isolated. PBMCs were grown
      with initial anti-CD3, low-dose interleukin-2 (IL-2), and peptide-pulsed DC
      stimulation. T-cell lines were analyzed in functional studies. RESULTS: After 4
      weeks, T-cell cultures were more than 50% CD8+. All peptide-pulsed T cells
      significantly lysed APC pulsed with the immunizing antigen in an HLA-A2
      restricted fashion. Furthermore, HLA-A2+,HER2/neu+ human pancreatic cancer cells
      were lysed significantly higher than HLA-A2 HER2/neu+ pancreatic cancer cells.
      Transfection of an HLA-A2 pancreatic cancer cell line with the HLA-A2 gene
      resulted in a significantly higher lysis of the transfected cell line compared to
      the wild type. In HLA-A2+ pancreatic cancer targets, specific lysis was HLA-A2
      restricted. CONCLUSION: The ability to use DCs for presentation of either tumor
      or peptide antigen in an HLA-restricted fashion to stimulate T-cell
      proliferation, as well as cytotoxicity, demonstrates the potential of this
      technology for future development of a pancreatic cancer vaccine.

PMID- 9288129
TI  - Endothelial cell apoptosis is accelerated by inorganic iron and heat via an
      oxygen radical dependent mechanism.
AB  - BACKGROUND: Iron participates in diverse pathologic processes by way of the
      Fenton reaction, which catalyzes the formation of reactive oxygen species (ROS).
      To test the hypothesis that this reaction accelerates apoptosis, we used human
      umbilical vein endothelial cells (HUVECs) as surrogates for the microvasculature
      in vivo. METHODS: HUVECs were loaded with Fe [III](ferric chloride and ferric
      ammonium citrate) with 8-hydroxyquinoline as carrier and were then challenged
      with two stimuli of the heat shock response, authentic heat or sodium arsenite.
      Iron dependence was tested with two chelators, membrane-impermeable deferoxamine
      and membrane-permeable o-phenanthroline. The role of ROS was assessed with
      superoxide dismutase, catalase, and the reporter compound dichlorofluorescein
      diacetate. The mechanism of cell death was assessed with three complementary
      techniques, Annexin V/propidium iodide labeling, the TUNEL stain, and electron
      microscopy. RESULTS: Iron-loaded HUVECs executed apoptosis after a heat shock
      stimulus. Iron-catalyzed formation of ROS appeared to be a critical mechanism,
      because both chelation of iron and enzymatic detoxification of ROS attenuated
      this apoptosis. CONCLUSIONS: Inorganic iron, in concert with chemical and
      physical inducers of the heat shock response, may trigger apoptosis. The
      accumulation of iron in injured tissue may thereby predispose to accelerated
      apoptosis and account, in part, for poor wound healing and organ failure.

PMID- 9288130
TI  - Adenoviral transfer of the inducible nitric oxide synthase gene blocks
      endothelial cell apoptosis.
AB  - BACKGROUND: We have previously reported that vascular inducible nitric oxide
      synthase (iNOS) gene transfer inhibits injury-induced intimal hyperplasia in
      vitro and in vivo. One mechanism by which NO may prevent intimal hyperplasia is
      by preserving the endothelium or promoting its regeneration. To study this
      possibility we examined the effect of iNOS gene transfer on endothelial cell (EC)
      proliferation and viability. METHODS: An adenoviral vector (AdiNOS) containing
      the human iNOS cDNA was constructed and used to infect cultured sheep arterial
      ECs. NO production was measured, and the effects of continuous NO exposure on EC
      proliferation, viability, and apoptosis were evaluated. RESULTS: AdiNOS-infected
      ECs produced 25- to 100-fold more NO than control (AdlacZ) infected cells as
      measured by nitrite accumulation. This increased NO synthesis did not inhibit EC
      proliferation as reflected by tritiated thymidine incorporation. Chromium 51
      release assay revealed that EC viability was also unaffected by AdiNOS infection
      and NO synthesis. In addition, prolonged exposure to NO synthesis did not induce
      EC apoptosis. Instead, NO inhibited lipopolysaccharide-induced apoptosis in these
      cells by reducing caspase-3-like protease activity. CONCLUSIONS: Vascular iNOS
      gene transfer, while inhibiting smooth muscle cell proliferation, does not impair
      EC mitogenesis or viability. Augmented NO synthesis may also protect ECs against
      apogenic stimuli such as lipopolysaccharide. Therefore iNOS gene transfer may
      promote endothelial regeneration and can perhaps accelerate vascular healing.

PMID- 9288132
TI  - Flow-induced arterial enlargement is inhibited by suppression of nitric oxide
      synthase activity in vivo.
AB  - BACKGROUND: Acute flow-induced arterial dilation is mediated by nitric oxide
      (NO). The role of NO in chronic flow-induced adaptive enlargement is unknown. We
      assessed the role of NO in arterial adaptation to increased blood flow (BF).
      METHODS: Iliac artery BF was increased in adult male rats by creating a left
      femoral arteriovenous fistula. Left iliac BF and diameter were measured, and wall
      shear stress was calculated. The effect of the NO synthase inhibitor N omega
      nitro-L-arginine-methyl ester (L-NAME) was studied in arteriovenous fistula rats
      divided into three groups (group 1, vehicle, group 2, 0.5 mg/ml; group 3, 2
      mg/ml) in drinking water. Arterial diameter, blood pressure, and medial cell
      density were assessed after 21 days. Left iliac cyclic guanosine monophosphate
      content was measured in an additional group of animals. RESULTS: BF and wall
      shear stress in the left iliac artery increased fourfold immediately after
      arteriovenous fistula. Arterial enlargement was evident after 7 days, and wall
      shear stress normalized after 42 days. Flow-induced arterial enlargement was
      inhibited by both low- and high-dose L-NAME compared with control (analysis of
      variance p < 0.05). Blood pressure was elevated only in animals treated with high
      dose L-NAME. Left iliac cyclic guanosine monophosphate content was lower in rats
      treated with L-NAME than in the control group (p < 0.05). CONCLUSIONS: NO
      suppression by L-NAME inhibits flow-induced iliac artery enlargement in rats.
      This finding suggests that NO plays a role in flow-induced arterial remodeling.

PMID- 9288131
TI  - Expression of matrix metalloproteinases and their inhibitors in aneurysms and
      normal aorta.
AB  - BACKGROUND: Abdominal aortic aneurysms (AAAs) are characterized by degradation of
      collagen and elastin resulting from increases in matrix metalloproteinase (MMP)
      activity. Previous authors have identified isolated increases in expression of
      specific MMPs in AAAs, but none have compared relative levels of expression of
      particular MMPs to one another or to those of their inhibitors, the tissue
      inhibitors of metalloproteinases (TIMPs). This study proposes to quantify
      relative mRNA levels for interstitial collagenase (MMP-1), 72 kd type IV
      collagenase (MMP-2), 92 kd type IV collagenase (MMP-9), TIMP-1, and TIMP-2 in
      normal aorta (NA) and AAA to provide insight as to the relative importance of
      each in aneurysm formation. METHODS: Competitive polymerase chain reactions
      (PCRs) with gene-specific external standards and cDNA derived from AAAs (n = 8;
      mean age, 67.4 years) and NA (n = 5; mean age, 40.6 years) were used to quantify
      mRNA levels. Results were normalized to glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) mRNA levels, determined by means of competitive PCR, and compared by
      means of Mann-Whitney statistics. RESULTS: Significant increases in MMP mRNA
      expression in AAA over NA were observed for MMP-1 (3.64 versus 0.3, p = 0.007),
      MMP-9 (78.03 versus 3.35, p = 0.003), TIMP-1 (835.32 versus 477.2, p = 0.027),
      and TIMP-2 (18.09 versus 4.14, p = 0.003). The ratio of MMP to TIMP mRNA levels
      was higher in AAA than NA (0.135 versus 0.045, p = 0.018). CONCLUSIONS: Increases
      in expression of MMP-1, MMP-9, and MMP/TIMP ratios may result in increased
      proteolysis and matrix degradation, which characterize AAAs. MMP-9 appears to be
      the predominant metalloproteinase expressed in AAA, because its mRNA levels were
      more than 20 times and 2 times higher than those of MMP-1 and MMP-2,
      respectively. TIMP-1 mRNA levels were in molar excess to those of any of the
      metalloproteinases studied.

PMID- 9288133
TI  - Obstructive jaundice in rats results in exaggerated hepatic production of tumor
      necrosis factor-alpha and systemic and tissue tumor necrosis factor-alpha levels
      after endotoxin.
AB  - BACKGROUND: Obstructive jaundice (OJ) predisposes patients to postoperative
      sepsis. We determined whether OJ led to an increased endotoxin stimulated tumor
      necrosis factor-alpha (TNF-alpha) production by macrophage-rich organs and
      whether a lack of intraluminal gut bile contributed to this increased
      sensitivity. METHODS: Rats underwent laparotomy and common bile duct ligation and
      division (CBDL) or sham operation after they were given low-dose endotoxin or
      saline solution (NS). TNF-alpha levels in plasma, perfusate from the isolated
      perfused rat liver, and tissue from lung, spleen, and liver were measured 90
      minutes later. An additional group underwent creation of a choledochal-vesical
      fistula and endotoxin administration. RESULTS: The plasma TNF-alpha, liver
      perfusate TNF-alpha, and the tissue TNF-alpha levels in liver, lung, and spleen
      were significantly elevated in the CBDL + endotoxin (CBDL + ETX) group compared
      with the SHAM + ETX and CBDL + NS groups (p < 0.05). The choledochal-vesical
      fistula group after endotoxin had plasma TNF-alpha levels only 27% that of the
      CBDL + ETX group (p < 0.05). CONCLUSIONS: OJ sensitizes macrophage-rich organs to
      produce larger amounts of TNF-alpha in response to endotoxin. This sensitization
      is not solely due to decreased intraluminal gut bile.

PMID- 9288134
TI  - Interleukin-10 reduces the systemic inflammatory response in a murine model of
      intestinal ischemia/reperfusion.
AB  - BACKGROUND: Intestinal ischemia/reperfusion (I/R) is known to increase systemic
      cytokine levels, as well as to activate neutrophils in distant organs. This study
      was designed to investigate the effect of interleukin-10 (IL-10) on cytokine
      release, pulmonary neutrophil accumulation, and histologic changes in a murine
      model of I/R. METHODS: Forty female Swiss-Webster mice were divided into four
      groups. Group 1 underwent 45 minutes of superior mesenteric artery occlusion
      followed by 3-hour reperfusion (I/R). Group 2 underwent laparotomy alone (Sham).
      Group 3 underwent I/R, but was treated with IL-10, 10,000 units IP every 2 hours,
      starting 1 hour before reperfusion (Pretreatment). Group 4 was treated with an
      equal dose of IL-10, starting 1 hour after reperfusion (Posttreatment). All
      animals were killed at 3 hours, standard assays were performed for serum cytokine
      levels, and lung myeloperoxidase activity and intestinal histology were scored.
      RESULTS: Serum cytokines (TNF-alpha and IL-6), lung myeloperoxidase levels, and
      histologic score were significantly reduced when IL-10 was administered either
      before or after reperfusion. CONCLUSIONS: IL-10 reduced the severity of local and
      systemic inflammation in a murine model of intestinal I/R when given before or
      after reperfusion injury. These observations suggest that IL-10 may exert its
      effect by blocking cytokine production and distant organ neutrophil accumulation.

PMID- 9288136
TI  - The novel chemokine mob-1: involvement in adult respiratory distress syndrome.
AB  - BACKGROUND: Using differential display reverse transcriptase-polymerase chain
      reaction we have recently identified mob-1, the novel rat homologue of the human
      alpha-chemokine IP-10, as a highly inducible gene in adult respiratory distress
      syndrome (ARDS) lungs. The present study aimed to further implicate mob-1 in the
      pathogenesis of ARDS. METHODS: Pulmonary mob-1 mRNA up-regulation was confirmed
      by Northern blot analysis in three different rat models of ARDS-like lung injury
      and localized to pulmonary macrophages by using in situ hybridization. Also,
      Escherichia coli-derived recombinant mob-1 (rmob-1) was tested for its properties
      in relationship to lung injury. RESULTS: In vivo, intratracheal injection of rmob
      1 (50 micrograms/rat) induced pulmonary leukosequestration (myeloperoxidase +93%
      +/- 8% versus control, p < 0.05) with preferential accumulation of neutrophils in
      bronchoalveolar lavage fluid (36.0% +/- 1.0% versus 0.1% +/- 0.1% in controls, p
      < 0.01). In vitro, transwell migration studies demonstrated chemotactic activity
      of rmob-1 (50 to 100 ng/ml) toward human monocytes (+151% +/- 34% versus rmob-1
      vehicle, p < 0.01) and only weak chemotaxis for human neutrophils (+15% +/- 0%
      versus rmob-1 vehicle, p < 0.01). Utilizing a rat aortic ring model ex vivo, rmob
      1 at 100 ng/ml exerted a very potent inhibitory effect on angiogenesis (-78.7% +/
      6.3% versus rmob-1 vehicle, p < 0.01), a major component of the resolution phase
      of ARDS. CONCLUSIONS: Taken together, these data support the involvement of mob-1
      in the pathogenic mechanisms of ARDS possibly through chemotaclic actions on
      inflammatory cells and modulation of angiogenesis in the recovery phase of the
      disease.

PMID- 9288135
TI  - Evidence for an unknown component of pancreatic ascites that induces adult
      respiratory distress syndrome through an interleukin-1 and tumor necrosis factor
      dependent mechanism.
AB  - BACKGROUND: The development of acute respiratory distress syndrome (ARDS) during
      acute pancreatitis is associated with interleukin (IL)-1 and tumor necrosis
      factor (TNF) gene expression within the pulmonary parenchyma. Although activated
      pancreatic enzymes have been thought to mediate pancreatitis-induced ARDS, they
      are not capable of inducing cytokine production in vitro. We hypothesized that IL
      1 and TNF production in the lungs is essential to the development of ARDS and is
      induced by a mediator released from the inflamed pancreas. METHODS: Pancreatic
      ascites was obtained from rats after induction of bile-salt pancreatitis,
      cultured, and assayed for IL-1, TNF, IL-6, IL-8, IL-10, interferon-gamma, and
      endotoxin. Sterile, cytokine-free ascites or saline (control) was subsequently
      administered intravenously (20 ml/kg) to healthy rats and to IL-1 R1 or TNF R1
      knockout mice. RESULTS: Animals administered intravenous ascites had a 30-fold
      rise in pulmonary IL-1 and TNF mRNA, as well as increased alveolar leukocytes and
      protein. Knockout animals devoid of active IL-1 or TNF receptors failed to
      develop increased alveolar protein or leukocytes. CONCLUSIONS: A component of
      pancreatic ascites other than activated enzymes, bacteria, or inflammatory
      cytokines is capable of inducing ARDS in healthy animals. The mechanism appears
      to be directly attributable to the activity of pulmonary IL-1 and TNF.

PMID- 9288138
TI  - Improving residents' clinical skills with the structured clinical instruction
      module for breast cancer: results of a multiinstitutional study. Breast Cancer
      Education Working Group.
AB  - BACKGROUND: The purpose of this study was to determine, in a multiinstitutional
      setting, the effectiveness of the structured clinical instruction module (SCIM)
      as an instructional format for surgical residents. METHODS: The breast cancer
      SCIM is an abbreviated (3-hour) clinical skills course that places residents in
      realistic clinical settings. The curriculum encompasses all aspects of breast
      cancer patient assessment. The SCIM was administered to 137 residents at five
      institutions. Sixty-six faculty members and 52 patients participated. All
      participants were surveyed with multiitem questionnaires. The residents were also
      asked to perform a self-assessment of their skills before and after the SCIM.
      RESULTS: The SCIM was delivered at all institutions without difficulty. All
      participants rated the SCIM highly (from "above average" to "outstanding"). Mean
      ratings (on a 5-point scale) for the overall effectiveness of the SCIM as an
      educational format follow: [table: see text] The pretest mean (on a 5-point
      scale) on the self-assessment was 2.46 ("less than competent"); the posttest mean
      was 3.54 ("more than competent") (p < 0.0001). CONCLUSIONS: Residents are acutely
      aware of their deficiencies in understanding breast cancer. The SCIM is a
      standardized, reproducible, portable, and effective educational vehicle.

PMID- 9288137
TI  - Distribution of pulmonary blood flow and total lung water during partial liquid
      ventilation in acute lung injury.
AB  - BACKGROUND: Gas exchange is improved during partial liquid ventilation (PLV) with
      perfluorocarbon in animal models of acute lung injury. The mechanisms are not
      fully defined. We hypothesize that redistribution of pulmonary blood flow (PBF)
      along with redistribution of, and decrease in, total lung water (TLW) during PLV
      may improve oxygenation. METHODS: We characterized PBF and TLW in anesthetized
      adult dogs by using positron emission tomography with H2(15)O. Measurements of
      gas exchange, PBF, and TLW were made before and after acute lung injury was
      induced with intravenous oleic acid. The same measurements were made during PLV
      (with 30 ml/kg perfluorocarbon) and compared with gas ventilated (GV) controls.
      RESULTS: Oxygenation was significantly improved during PLV. PBF redistributed
      from the dependent zone of the lung to the nondependent zones, thus potentially
      improving ventilation/perfusion relationships. However, a similar pattern of PBF
      redistribution was observed during GV such that there was no significant
      difference between groups. TLW redistributed in a similar pattern during PLV. By
      quantitative measurements, PLV ameliorated the continued accumulation of TLW
      compared with GV animals. CONCLUSIONS: We conclude that PBF and TLW
      redistribution and attenuation of increases in TLW may contribute to the
      improvement in gas exchange during PLV in the setting of acute lung injury.

PMID- 9288139
TI  - A new assessment tool: the patient assessment and management examination.
AB  - BACKGROUND: The major goal of certification is to assure the public that the
      candidate is competent in all facets required of the position. The patient
      assessment and management examination (PAME) was developed to enable a more
      comprehensive assessment of competence in the practice of surgery. METHODS: A six
      station, 3-hour, standardized-patient-based evaluation was developed. Each
      station was scored using a set of five-point global rating scales. PAME results
      were compared to the last two in training evaluation reports (ITER), the clinical
      knowledge component of the ITER (ITER-CK), an in-house oral examination (OE), and
      the Canadian Association of General Surgeons' multiple-choice examination (CAGS).
      RESULTS: Eighteen senior general surgery residents were evaluated. Overall
      reliability was 0.70 (Cronbach's alpha). Fifth-year residents scored
      significantly better than fourth-year residents (t = 3.062; p = 0.0074), with 1
      year of training accounting for 37% of the variance in scores. Correlations
      between the PAME and each of the other measures were ITER, 0.24; ITER-CK, 0.38;
      OE, -0.13; and CAGS, 0.061, with the PAME demonstrating better reliability and
      stronger evidence of validity than any other. CONCLUSIONS: The PAME had better
      psychometric properties than other measures and assessed areas often not
      evaluated. This type of evaluation may be useful for feedback, remediation, or
      certification decisions.

PMID- 9288140
TI  - Increased mediastinal pressure and decreased cardiac output during laparoscopic
      Nissen fundoplication.
AB  - BACKGROUND: Laparoscopic Nissen fundoplication (LNF) is gaining popularity.
      Although the hemodynamic effects of the typical pneumoperitoneum have been
      studied, the additional consequences of the hiatal dissection necessary for LNF
      have not. METHODS: Seven female pigs were anesthetized, intubated, and ventilated
      with a volume ventilator and hemodynamic and mechanical pressure monitoring
      devices were placed. Pressures were recorded every 15 minutes for 1 hour after
      each of four interventions: (1) anesthesia induction, (2) CO2 pneumoperitoneum
      (15 mm Hg), (3) LNF, and (4) release of pneumoperitoneum (and removal of ports).
      RESULTS: Right atrial, inferior vena caval, mediastinal, pleural, airway, and
      pulmonary capillary wedge pressures all increased after pneumoperitoneum (p <
      0.05). Only mediastinal pressure (8.6 vs 13.7 mm Hg, pneumoperitoneum vs LNF; p <
      0.05) and pleural pressure (2.6 vs 3.5 mm Hg, pneumoperitoneum vs LNF; p < 0.05)
      showed a further significant increase after LNF. In addition, cardiac output fell
      significantly after LNF (5.9 vs. 4.6 L/min; p < 0.05). Mediastinal pressure and
      cardiac output remained significantly altered after the release of
      pneumoperitoneum. CONCLUSIONS: Surgical disruption of the esophageal hiatus
      during LNF causes both increased mediastinal and pleural pressure and a
      significant reduction in cardiac output. These findings uncover a previously
      unsuspected physiologic detriment that may occur during LNF.

PMID- 9288141
TI  - Iron deficiency enhances cholesterol gallstone formation.
AB  - BACKGROUND: Cholesterol gallstones occur most commonly in multiparous women, but
      the causes for this phenomenon remain unclear. This same patient population is
      prone to chronic iron deficiency anemia. In addition, iron is known to play an
      important role in hepatic enzyme metabolism. Therefore, we tested the hypotheses
      that iron deficiency would alter hepatic cholesterol metabolism and enhance
      gallstone formation. METHODS: Forty adult prairie dogs were fed either a control
      iron-supplemented (200 ppm), an iron-deficient (8 ppm), a 0.4% cholesterol iron
      supplemented (200 ppm), or a 0.4% cholesterol iron-deficient (8 ppm) diet. After
      8 weeks gallbladder bile, serum, and liver were harvested. Gallbladder bile was
      examined for cholesterol crystals and gallstones. Bile lipids and hepatic enzymes
      were measured, and a cholesterol saturation index (CSI) was calculated. RESULTS:
      Animals receiving the iron-deficient diet were more likely to have cholesterol
      crystals in their bile than were animals on the control diet (80% vs. 20%; p <
      0.05). Animals on the 0.4% cholesterol iron-deficient diet had more cholesterol
      crystals per high-powered field (79 +/- 10 vs. 49 +/- 9; p = 0.07), a higher
      molar % cholesterol (6.0 +/- 0.3 vs 4.4 +/- 0.5; p < 0.05), and a higher CSI
      (1.27 +/- 0.10 vs. 0.91 +/- 0.07; p < 0.05) compared to animals receiving the
      0.4% cholesterol iron supplemented diet. The 7 alpha-hydroxylase levels were
      lower in the animals on the iron-deficient diet compared to those receiving the
      control diet (0.42 +/- 0.08 vs 1.17 +/- 0.40 pmol/mg per minute; p = 0.07).
      CONCLUSIONS: These data suggest that an iron-deficient diet (1) alters hepatic
      enzyme metabolism, which, in turn, (2) increases gallbladder bile cholesterol and
      promotes cholesterol crystal formation. We conclude that iron deficiency plays a
      previously unrecognized role in the pathogenesis of cholesterol gallstone
      formation in women.

PMID- 9288143
TI  - Antiproliferative and antiinvasive effects of carboxyamido-triazole on breast
      cancer cell lines.
AB  - BACKGROUND: Basement membrane invasion is one of the critical components of the
      metastatic cascade. The antiproliferative and antiinvasive activity of
      carboxyamido-triazole (CAI), a calcium influx inhibitor, was studied in five
      human breast cancer cell lines (MCF-7, MCF-7/ADRR, MDA-231, MDA-231R44, and BT
      474). METHODS: Sensitivity of the cell lines to CAI was measured with a
      microculture tetrazolium assay. The Boyden chamber Matrigel chemoinvasion assay
      was used to measure the antiinvasive activity of CAI. Matrix metalloproteinase
      activity was analyzed by gelatin zymography. RESULTS: The 50% inhibitory
      concentrations of CAI were cell line dependent and ranged from 7.49 +/- 4.05
      mumol/L to 46.1 +/- 8.6 mumol/L. CAI at a low, minimally toxic concentration (5
      mumol/L) inhibited invasion by greater than 75% in the four invasive cell lines
      (MCF-7/ADRR, MDA-231, MDA-231R44, and BT-474) regardless of estrogen receptor or
      p-glycoprotein status (p < 0.01). CAI treatment also reduced matrix
      metalloproteinase activity in conditioned media from three of the four invasive
      lines (p < 0.05). CONCLUSIONS: CAI at clinically achievable concentrations is an
      effective antiproliferative and antiinvasive agent against human breast cancer
      cell lines regardless of estrogen receptor or p-glycoprotein status. Reduction in
      matrix metalloproteinase activity may be partially responsible for CAI inhibition
      of invasion.

PMID- 9288142
TI  - "Cold" single-strand conformational variants for mutation analysis of the RET
      protooncogene.
AB  - BACKGROUND: RET protooncogene mutation analysis is a routinely performed
      predictive DNA test in kindreds affected by multiple endocrine neoplasia (MEN)
      types 2A and 2B and familial medullary thyroid carcinoma (FMTC), and is a
      valuable diagnostic tool in newly diagnosed cases of medullary thyroid carcinoma
      (MTC). METHODS: We tested the suitability of the recently introduced "cold"
      single-strand conformational variant (SSCV) technique, which promises rapid,
      simple, nonradioactive detection of sequence variants in the identification of
      germline and somatic RET mutations. A total of 11 different mutations in exon 10
      (codons 609, 611, 618, and 620) and 6 mutations in exon 11 (codon 634) were
      studied. RESULTS: Conditions were optimized so that conformational variants were
      demonstrated for all mutations examined in a single setting for exons 10 and 11.
      A novel six base pair (bp) inframe deletion between cysteines 630 and 634 was
      detected in a sporadic MTC. This adds to the evidence that not only cysteine
      deletions and substitutions but also changes in the spacing between cysteine
      residues have a pathogenic effect. CONCLUSIONS: Our results indicate that the
      cold SSCV method offers the advantages of simplicity, time savings, and
      nonradioactive detection for screening for RET sequence variants in hereditary
      and sporadic MTCs.

PMID- 9288144
TI  - Design of a potent novel endotoxin antagonist.
AB  - BACKGROUND: Bactericidal permeability increasing protein (BPI) binds to and
      neutralizes lipopolysaccharide (LPS, endotoxin). Small synthetic peptides based
      on the amino acid sequence of the LPS binding domain of BPI neutralize LPS,
      albeit inefficiently. Although the LPS binding domain of native BPI possesses a
      beta-turn secondary structure, this structure is not present in small derivative
      peptides. The purpose of this study was to determine whether the addition of a
      beta-turn to a BPI-derived peptide is associated with more potent endotoxin
      antagonism. METHODS: We generated a hybrid peptide (BU3) on the basis of (1) a
      portion of the LPS binding domain from BPI and (2) amino acids known to initiate
      a beta-turn. BU3 folds with a beta-turn, and we tested its effects on LPS
      neutralization and LPS-induced tumor necrosis factor-alpha secretion, comparing
      it with BPI-derived peptide BG22 that lacks a beta-turn and to an irrelevant
      peptide (BG16). RESULTS: Compared with BG22, BU3 demonstrated enhanced LPS
      neutralization and inhibition of LPS-induced tumor necrosis factor-alpha
      secretion in vitro and a similar diminution of endotoxemia and tumor necrosis
      factor-alpha secretion in a murine model of endotoxemia. CONCLUSIONS: These data
      demonstrate the potential for enhancing the biologic activity of a BPI-derived
      peptide endotoxin antagonist via manipulation of its conformational structure.

PMID- 9288145
TI  - Cholecystokinin modulates mucosal immunoglobulin A function.
AB  - BACKGROUND: We have established that mucosal immunoglobulin A (IgA) production is
      highly dependent on cholecystokinin release and is markedly suppressed by
      glucocorticoids. The purpose of the present study was to examine the role of
      cholecystokinin on the functional responsiveness of the mucosal IgA system in
      glucocorticoid treated rats. METHODS: A total of 24 Fischer rats were assigned to
      three groups of 8 animals each. Animals were injected with vehicle (CON),
      dexamethasone (DEX) (0.08 mg/150 g), or DEX (0.08 mg/150 gm) and ARL1294KF (500
      ng twice daily), a novel and potent long-acting cholecystokinin agonist
      (DEX+CCK). Animals were treated for 48 hours and killed. Duodenum was harvested,
      and the total mucosal concentration of cholecystokinin was measured by
      radioimmunoassay. Mucosal IgA was assayed by quantitation of immunoreactive cells
      in the ileum. Bacterial adherence was evaluated by quantitative culture of
      vigorously washed stripped cecal mucosa. Transepithelial electrical resistance, a
      measure of tight junction permeability, was assessed by mounting strips of
      adjacent cecal mucosa in Ussing chambers. RESULTS: Glucocorticoid administration
      resulted in a statistically significant (p < 0.001) decrease in duodenal
      cholecystokinin, decreased IgA, and impaired mucosal immunity (increased
      bacterial adherence and decreased tissue resistance). Cholecystokinin
      administration preserved mucosal immune function in DEX-treated rats.
      CONCLUSIONS: Cholecystokinin may play an important role in maintaining the
      functional responsiveness of mucosal immunity during catabolic stress.

PMID- 9288147
TI  - Effect of a dominant negative ras on myocardial hypertrophy by using adenoviral
      mediated gene transfer.
AB  - BACKGROUND: The small guanosine triphosphate-binding protein ras regulates a
      signal transduction cascade linking cell surface receptors to mitogen-activated
      protein kinase (MAPK). Because the molecular signaling mechanisms underlying
      cardiac hypertrophy remain unclear, the current study examined the regulatory
      role of ras in both the biochemical and morphologic aspects of hypertrophy.
      METHODS: Adenoviral-mediated gene transfer was used to express a dominant
      negative mutant of ras (rasN17) at high efficiency in primary neonatal
      ventricular myocytes. Beta-galactosidase staining and Western blot analysis
      confirmed successful transfection and expression of the rasN17 gene product. MAPK
      activity was measured by an in vitro kinase assay resulting in radioactive
      phosphorus labeled product. Morphologic hypertrophy was assessed by fluorescein
      conjugated phalloidin. RESULTS: Compared with uninfected or control adenoviral
      infected cells, myocytes infected with rasN17 demonstrated attenuated basal MAPK
      activity. In contrast, rasN17 expression did not affect endothelin 1-induced MAPK
      activation. Morphologic studies showed that although rasN17 produced a phenotypic
      difference in the basal state, the ability of cardiac myocytes to morphologically
      respond to endothelin 1 stimulation, as manifested by sarcomeric reorganization,
      remained unaltered by the expression of the rasN17 gene product. CONCLUSIONS:
      Endothelin 1-stimulated MAPK activation and endothelin 1-induced morphologic
      hypertrophy are ras-independent processes.

PMID- 9288146
TI  - Endotoxin-mediated synthesis of nitric oxide is dependent on Gq protein signal
      transduction.
AB  - BACKGROUND: Nitric oxide (NO) is a ubiquitous multifunctional free radical
      produced during sepsis, shock, reperfusion injury, and allograft rejection. Many
      studies are presently evaluating the functional roles of NO production in these
      settings. However, the signal transduction mechanisms underlying initiation of NO
      production are largely unknown. This study defines the cell surface receptor
      proteins that mediate endotoxin-induced NO synthesis in ANA-1 murine macrophages.
      METHODS: Endotoxin (LPS, 10 micrograms/ml) was added to ANA-1 macrophages to
      induce NO synthesis. In selected instances guanosine 5'-O-(2-thiodiphosphate)
      trilithium salt (GOTP), pertussis toxin, cholera toxin, or suramin were added as
      inhibitors of specific subclasses of heterotrimeric G proteins. Calphostin was
      added as a protein kinase C inhibitor, and ET-OCH3 was added as a phospholipase C
      beta inhibitor. NO release was quantified by measurement of the NO metabolite,
      nitrite. Membrane guanosine triphosphatase (GTPase) activity was also analyzed.
      Steady-state levels of inducible nitric oxide synthase (iNOS) mRNA were
      determined by using reverse transcription-polymerase chain reaction analysis.
      RESULTS: Inhibition of G protein function by suramin or GOTP significantly
      decreased synthesis of NO and expression of iNOS mRNA. Pertussis and cholera
      toxin did not alter NO synthesis, suggesting that the Gi and Gs classes are not
      involved. Inhibition of protein kinase C or upstream phospholipase C-beta
      activity decreased NO synthesis, implicating the Gq class of heterotrimeric G
      proteins. CONCLUSIONS: In ANA-1 macrophages, endotoxin-mediated NO synthesis is
      dependent on heterotrimeric Gq protein-phospholipase C-beta-protein kinase C
      signal transduction.

PMID- 9288149
TI  - Loss of endothelial barrier function requires neutrophil adhesion.
AB  - BACKGROUND: The inflammatory response is characterized by cytokine-induced up
      regulation of endothelial adhesion molecules followed by polymorphonuclear
      neutrophil (PMN) adhesion and breakdown of tight junctions between cells. The
      purpose of this investigation was to determine whether PMN adhesion is an
      essential element in the alteration of endothelial permeability or whether
      cytokines alone can produce this change. METHODS: Human umbilical vein
      endothelial cells (HUVECs) were exposed to formylated met-leu-phe-activated PMNs.
      In a second series of experiments, PMNs were contained in a microporous membrane
      that allowed passage of secreted cytokines but not cells. Permeability was
      quantified by using transendothelial electrical resistance (TEER, ohm.cm2,)
      whereas expressions of two cell adhesion molecules (endothelial leukocyte
      adhesion molecule-1 [ELAM-1] and intercellular adhesion molecule-1 [ICAM-1]) were
      measured by flow cytometry (% shift). Cytokine production was monitored with
      enzyme-linked immunosorbant assays (picograms per milliliter). RESULTS:
      Stimulated PMNs secreted comparable amounts of cytokines whether allowed access
      to HUVECs or trapped in a microporous membrane (interleukin-1 alpha, 5.88 +/-
      2.38 versus 3.65 +/- 1.84 pg/ml; tumor necrosis factor-alpha, 10.27 +/- 3.21
      versus 6.61 +/- 1.82 pg/ml). Up-regulation of ELAM-1 and ICAM-1 was observed
      whether PMNs were free or restricted (52.97% +/- 2.14% versus 75.32% +/- 4.19%
      and 71.66% +/- 7.37% versus 73.66% +/- 4.32%, respectively). TEER was unchanged
      in controls and when PMNs were membrane restricted. In contrast, TEER decreased
      precipitously (51% +/- 5.9% of control, p < 0.05) if PMNs were allowed access to
      HUVECs. CONCLUSIONS: Cytokine secretion by PMNs is independent of endothelial
      contact and is sufficient to upregulate adhesion molecules. However, PMN adhesion
      is essential for the loss of endothelial barrier function, which leads to
      diapedesis of activated PMNs and eventual tissue injury.

PMID- 9288148
TI  - Hemodynamic alteration by fetal surgery accelerates myocyte proliferation in
      fetal guinea pig hearts.
AB  - BACKGROUND: Fetal heart development occurs by hyperplasia as myocytes lose the
      capacity to proliferate at birth. This potential for cell division may have
      application in altering fetal growth patterns in congenital cardiac
      malformations, but it is not known whether the proliferative activity can be
      modified by intrauterine surgical manipulation. The purpose of this study was to
      determine whether hemodynamic alteration by fetal surgery influences myocyte
      proliferation and myocardial development. METHODS: Six pregnant guinea pigs of 50
      to 52 days of gestation (term, 65 days) underwent hysterotomy, and the fetal
      ascending aorta was banded and narrowed by 50% (AoB). Cesarean section was
      performed near term, and the heart was assessed for myocyte proliferative
      activity (Ki-67 monoclonal antibody), apoptosis, and morphologic features.
      RESULTS: The heart to body weight ratio (1.02% +/- 0.12% versus 0.42% +/- 0.02%,
      p < 0.01) and left ventricular posterior wall thickness (1.89 +/- 0.25 mm versus
      1.31 +/- 0.19 mm, p < 0.01) were significantly higher in the AoB group. The
      percentage of Ki-67 positive cells was increased in AoB group (29.5% +/- 4.4%
      versus 15.3% +/- 1.3% in right ventricle, 35.8% +/- 5.1% versus 13.1% +/- 1.7% in
      interventricular septum, and 39.8% +/- 3.2% versus 12.0% +/- 2.0% in left
      ventricle (p < 0.01). The apoptotic cell to myocyte ratio was less than 1/1000 in
      both groups. CONCLUSIONS: Fetal hemodynamic alteration by aortic banding
      accelerates myocardial cellular proliferation without affecting apoptosis,
      suggesting that in utero cardiac interventions have a greater influence on
      myocardial development compared with postnatal intervention.

PMID- 9288150
TI  - Adenoviral-mediated gene transfer of a constitutively active retinoblastoma gene
      inhibits human pancreatic tumor cell proliferation.
AB  - BACKGROUND: The development of pancreatic cancer involves an accumulation of
      genetic changes, including oncogene activation and mutations in tumor suppressor
      genes important in cell cycle regulation. As a step to developing gene therapies
      to restore cell cycle control, we hypothesized that adenoviral-mediated gene
      transfer of a constitutively active, nonphosphorylatable form of the
      retinoblastoma gene (AdRb) would inhibit human pancreatic tumor cell
      proliferation. METHODS: Transfection efficiency was assessed by beta-gal staining
      with an adenovirus expressing the beta-galactosidase gene (AdLacZ). The effect of
      AdRb on DNA synthesis in pancreatic cancer cell lines was determined by tritiated
      thymidine incorporation. Western blotting with an antihemagglutinin antibody
      directed to the hemagglutinin-tagged AdRb construct was performed to confirm
      transfection of pancreatic cancer cells. Apoptosis was evaluated with a TUNEL
      assay. RESULTS: Efficient transfection of human pancreatic cancer cell lines was
      achieved with AdLacZ. AdRb inhibited tritiated thymidine uptake in the cancer
      cell lines BxPC-3, MIA PaCa-2, and PANC-1. Western blotting confirmed
      transfection of cancer cells with AdRb. AdRb did not inhibit growth by apoptosis.
      CONCLUSIONS: Adenoviral-mediated gene delivery of constitutively active Rb
      produces significant growth inhibition in human pancreatic cancer cell lines and
      is not a result of apoptosis. Further studies examining the role of Rb in
      pancreatic cancer are warranted.

PMID- 9288151
TI  - Excellence of the two-layer method (University of Wisconsin
      solution/perfluorochemical) in pancreas preservation before islet isolation.
AB  - BACKGROUND: In islet transplantation pancreatic preservation before islet
      isolation is an obstacle compromising islet yield and viability. We tested the
      feasibility of a two-layer method (University of Wisconsin solution
      [UW]/perfluorochemical) for pancreatic preservation before islet isolation.
      METHODS: Dog pancreases were processed into pure islets by the method of Ricordi
      preceded by five different preservations (groups 1-a and 1-b, the two-layer
      method for 3 and 24 hours; groups 2-a and 2-b, simple cold storage in UW for 3
      and 24 hours; group 3, without preservation). Islet yields and functional success
      after autotransplantation into the liver were compared among the groups. RESULTS:
      Postpurification islet equivalents (IE)/gm pancreas and functional success rate
      were 5600 (mean), 83% in group 1-a; 4000, 56% in group 1-b; 4700, 33% in group 2
      a; 1300, 0% in group 2-b; and 5000, 89% in group 3 (p < 0.05; 2b versus 1-a, 1-b,
      and 3), respectively. There was no statistical difference among groups 1-a, 1-b,
      and 3 in terms of islet yield and function (p > 0.2). CONCLUSIONS: The two-layer
      method is more effective than conventional simple cold storage in UW for
      pancreatic preservation before islet isolation. Clinical trials with the two
      layer method are warranted.

PMID- 9288152
TI  - An ETa/ETb endothelin antagonist ameliorates systemic inflammation in a murine
      model of acute hemorrhagic pancreatitis.
AB  - BACKGROUND: Endothelin peptides are polykines with strong vasoconstrictor
      properties. We have previously shown that endothelin antagonism (PD145065)
      reduces the local severity of acute pancreatitis. We now investigated the effect
      of endothelin antagonism on systemic inflammation in a model of acute hemorrhagic
      pancreatitis. METHODS: Forty-two mice were divided into four groups. Group 1 was
      fed standard food plus PD145065 every 8 hours. Group 2 was fed a choline
      deficient ethionine (CDE) supplemented diet and given saline every 8 hours. Group
      3 was fed a CDE diet and treated with PD145065 every 8 hours from initiation of
      diet. Group 4 was fed a CDE diet and given PD145065 from 48 hours after
      initiation of diet. Animals were killed at 70 hours. Serum was collected.
      Pancreata and lung tissue were harvested. RESULTS: Histology score, serum amylase
      level, lung myeloperoxidase, and interleukin (IL)-10 were all significantly
      reduced in both treatment groups (groups 3 and 4) (p < 0.05). IL-6 levels were
      reduced in group 3 only (p < 0.05). The mortality rate did not differ among any
      of the groups. CONCLUSIONS: Endothelin antagonism decreased the severity of acute
      pancreatitis and reduced markers of systemic inflammation. Late treatment at 48
      hours failed to prevent the rise in IL-6. Mortality rates were unaffected by
      treatment.

PMID- 9288154
TI  - PACAP-38 causes phospholipase C-dependent calcium signaling in rat acinar cell
      line.
AB  - BACKGROUND: Pituitary adenylate cyclase activating peptide (PACAP-38), a
      neuropeptide of the vasoactive intestinal peptide/secretin family, localizes to
      intrapancreatic neurons and stimulates exocrine secretion from the pancreas.
      PACAP-38 stimulates calcium signaling in the rat pancreatic cell line AR42J. The
      purpose of this study was to elucidate the mechanisms of PACAP-evoked calcium
      signaling in these cells. METHODS: Continuous measurements of intracellular
      calcium were taken by fluorescent digital microscopy with the dye fura-2.
      Mechanisms of PACAP-38-evoked calcium signals were determined by a panel of
      inhibitors. Inositol phosphates production in response to PACAP-38 was measured.
      The ability of PACAP-38 to stimulate amylase release was used to determine a
      relevant dose range for these studies. RESULTS: We have shown that (1) AR42J
      cells respond to PACAP-38 with biphasic increases in [Ca2+]i in a dose-dependent
      fashion; (2) PACAP-38 acts through phospholipase C to release inositol
      triphosphate (IP3)-sensitive Ca2+ stores with (3) a subsequent influx of
      extracellular Ca2+. CONCLUSIONS: PACAP-38 activates calcium signaling through
      phospholipase C at concentrations that stimulate amylase release in AR42J cells.

PMID- 9288153
TI  - Regulation of glutamine synthetase in human breast carcinoma cells and
      experimental tumors.
AB  - BACKGROUND: Acute deprivation of extracellular glutamine causes up-regulation of
      glutamine synthetase (GS) expression by a mechanism involving an increase in GS
      protein stability. This study examines GS expression in a highly glutamine
      dependent and tumorigenic human breast cancer cell line, TSE cells, in response
      to acute and chronic glutamine deprivation in culture and during tumor formation.
      METHODS: TSE cells were subjected to acute glutamine deprivation, adapted to
      growth in low glutamine concentrations, and subcutaneously injected into nude
      mice. GS protein and mRNA levels were assayed by Western and Northern blotting,
      and intracellular glutamine levels were evaluated by using a colorimetric assay.
      RESULTS: GS protein levels increased, but GS mRNA levels were unchanged in
      response to acute glutamine deprivation. Chronic glutamine deprivation in vitro
      and tumor growth in vivo caused an increase in both GS protein and mRNA levels.
      Large tumors exhibited lower intracellular glutamine, higher GS protein, and
      relatively unchanged GS mRNA levels relative to small tumors. CONCLUSIONS: TSE
      tumors exhibit up-regulation of GS protein and mRNA levels and declines in
      intracellular glutamine content, suggesting that growth in vivo causes a chronic
      and progressive glutamine deprivation. Up-regulation of GS expression may
      contribute to adaptation to a nutrient-poor intratumor environment.

PMID- 9288155
TI  - The pancreatic duct epithelium in vitro: bile acid injury and the effect of
      epidermal growth factor.
AB  - BACKGROUND: Pancreatic duct epithelial cells form a barrier against parenchymal
      injury. The capacity of these cells to respond to injury has not been
      investigated. We hypothesized that epidermal growth factor (EGF), normally found
      in pancreatic juice, could protect the duct epithelium from damage. METHODS: An
      explant system of duct cell culture developed in our lab with the bovine main
      pancreatic duct was used. Explants were exposed to bile acid (taurodeoxycholic
      acid [TDCA] 0, 0.05, 0.5, and 1 mmol/L) in the presence or absence of EGF (0, 1,
      10, and 100 nmol/L) for 48 hours. Epithelial proliferation, damage, and growth
      out from the explant edge were assessed histologically. Expression of ductal
      markers and the extent of cell proliferation were determined by
      immunohistochemistry using specific antibodies. RESULTS: Explant duct cells
      proliferated and demonstrated continued expression of key duct antigens in
      culture. TDCA produced dose-dependent mucosal damage and reduced epithelial
      density and growth from the edge. EGF increased cellular density in the native
      epithelium, but did not significantly alter growth from the edge. Mucosal damage
      created by TDCA exposure was significantly decreased with EGF and both growth
      from the edge and cell density were preserved. CONCLUSIONS: Explants created from
      the bovine main pancreatic duct serve as an excellent model for the study of duct
      epithelial cells in vitro. These cells proliferate in response to EGF and are
      damaged by TDCA at concentrations below those normally associated with detergent
      like activity and below levels observed in bile and duodenal secretions. The
      ability of EGF to protect from this injury suggests a potential physiologic role
      in the maintenance of the pancreatic duct mucosal barrier.

PMID- 9288156
TI  - Nitric oxide-induced hyperpermeability of human intestinal epithelial monolayers
      is augmented by inhibition of the amiloride-sensitive Na(+)-H+ antiport:
      potential role of peroxynitrous acid.
AB  - BACKGROUND: Nitric oxide (NO.) increases the permeability of cultured intestinal
      epithelial monolayers. NO. reacts with superoxide anion to form peroxynitrite
      anion, which can be protonated under mildly acidic conditions to form the potent
      and versatile oxidizing agent, peroxynitrous acid. We hypothesized that
      intracellular acidosis induced by the Na(+)-H+ antiport blocker, amiloride, would
      favor the formation of peroxynitrous acid and thereby augment hyperpermeability
      induced by the NO. donor, SIN-1. METHODS: Caco-2BBe human intestinal epithelial
      monolayers were grown on permeable supports in bicameral chambers. The
      permeability of monolayers was assessed by measuring the transepithelial flux of
      fluorescein disulfonic acid (FS). RESULTS: Incubation of monolayers with SIN-1
      increased permeability to FS. Adding amiloride augmented SIN-1-induced
      hyperpermeability. SIN-1 plus amiloride also decreased cellular adenosine
      triphosphate content and caused derangements of the actin-based cytoskeleton as
      demonstrated by fluorescence microscopy. Coincubation of monolayers with several
      free-radical or peroxynitrous acid scavengers (deferoxamine, mannitol, dimethyl
      sulfoxide, or ascorbate) ameliorated hyperpermeability induced by SIN-1 plus
      amiloride. CONCLUSIONS: Amiloride augments NO.-induced intestinal epithelial
      permeability, apparently by promoting the development of intracellular acidosis
      and thereby favoring the formation of the peroxynitrous acid.

PMID- 9288157
TI  - Thrombospondin-1 and transforming growth factor-beta l promote breast tumor cell
      invasion through up-regulation of the plasminogen/plasmin system.
AB  - BACKGROUND: Pericellular proteolysis is crucial in tumor cell invasion. The
      plasminogen/plasmin system is one of the main protease systems involved in cancer
      progression. Thrombospondin-1 (TSP-1), through activation of transforming growth
      factor-beta 1 (TGF-beta 1), up-regulates the main plasminogen activator, the
      urokinase-type plasminogen activator (uPA). The objectives of this study were to
      determine the role of TSP-1 and TGF-beta 1 in the localization of the
      plasminogen/plasmin system to the tumor cell surface by the uPA receptor (uPAR)
      and to determine its effect in breast tumor cell invasion. METHODS: The effect of
      TSP-1 and TGF-beta 1 in uPAR expression was determined in MDA-MB-231 human breast
      cancer cells by enzyme-linked immunosorbent assay and Western blot analysis.
      Their effect and the role of the plasminogen/plasmin system in breast tumor cell
      invasion were studied with a Boyden Chamber assay. RESULTS: uPAR expression was
      up-regulated more than twofold by both TSP-1 and TGF-beta 1. The effect of TSP-1
      involved its receptor and the activation of TGF-beta 1 by TSP-1. Breast tumor
      cell invasion was up-regulated sevenfold to eightfold by both TSP-1 and TGF-beta
      1 compared with the control group. Antibodies against uPA or uPAR neutralized the
      TSP-1- and TGF-beta 1-promoted breast tumor cell invasion. CONCLUSIONS: TSP-1,
      through the activation of endogenous TGF-beta 1, up-regulates the
      plasminogen/plasmin system and promotes tumor cell invasion in breast cancer
      cells.

PMID- 9288158
TI  - Regulation of vascular endothelial growth factor expression in human colon
      carcinoma cells by activity of src kinase.
AB  - BACKGROUND: The c-src protooncogene encodes a protein tyrosine kinase, pp60c-src,
      that is a mediator in many signal transduction pathways. One pathway in which
      pp60c-src protein tyrosine kinase activity is implicated involves regulation of
      vascular endothelial growth factor (VEGF), an angiogenic factor important to
      neovascularization of growing tumors. Recently we demonstrated that decreased
      activity of pp60c-src in colon tumor cells contributes to decreased expression of
      VEGF. This study examined the relationship between pp60c-src activation, cell
      density, and VEGF production in a colon tumor cell line. METHODS: Parental HT-29
      colon adenocarcinoma cells and stable subclones created by transfection with c
      src antisense and sense (control) expression vectors were plated under sparse (2
      x 10(4) cells/cm2) and confluent (20 x 10(4) cells/cm2) conditions and grown for
      36 hours. Protein and RNA were extracted from cells to determine pp60c-src
      levels, c-Src tyrosine kinase activity, and VEGF mRNA expression. RESULTS: The
      pp60c-src kinase activity of HT-29 cells and control sense-transfected clones
      grown under confluent conditions was increased threefold to fivefold compared
      with cells grown under sparse conditions. In contrast, the ability of confluent
      culture conditions to increase pp60c-src activity was blunted in antisense
      transfectants. By regression analysis, VEGF expression was found to vary directly
      with pp60c-src levels (r2 = 0.886). CONCLUSIONS: Cell density contributes to the
      regulation of c-src kinase activity and VEGF expression in HT-29 cells. When the
      steady-state level of pp60c-src is reduced in antisense transfectants, not only
      is the steady-state level of VEGF reduced, but the ability of confluence to
      stimulate pp60c-src activity and VEGF production is too. These data suggest that
      c-src may be an intermediary of both constitutive and inducible pathways for VEGF
      production in colon tumor cells.

PMID- 9288160
TI  - New approaches to antiglaucoma therapy.

PMID- 9288159
TI  - Breast cancer increases initiation of angiogenesis without accelerating neovessel
      growth rate.
AB  - BACKGROUND: Recurrence and mortality rates in patients with breast cancer
      correlate with the degree of tumor angiogenesis (angiogenic index). We have
      developed a novel angiogenesis model by using disks of fresh human placental vein
      that initiate an angiogenic response and exhibit linear radial capillary growth
      in culture. We hypothesized that the addition of human breast cancer cells to
      this human placental vein angiogenesis model would increase the incidence of
      angiogenesis and accelerate the rate of neovessel growth compared with vein disk
      cultured without tumor cells. METHODS: To test this hypothesis, vein explants
      from seven human placentas were incorporated into clots of 0.3% fibrin in Medium
      199 and fetal bovine serum with or without 1.5 x 10(5) T-47D (n = 6 placentas) or
      MCF-7 (n = 1 placenta) breast cancer cells. Statistical differences between the
      experimental (with breast cancer cells) and control (no added cells) cultures
      were determined by repeated measures ANOVA. RESULTS: The proportion of disks
      exhibiting neovessel growth (initiation) by day 12 was significantly increased in
      the presence of T-47D cells (p < 0.05 at day 12, p < 0.001 at day 15). No
      statistical difference was seen in rates of neovessel growth (millimeters per
      day). Similar results were seen with MCF-7 cells. CONCLUSIONS: Tumor enhancement
      of angiogenesis may occur by increased initiation of the angiogenic response.
      Subsequent vessel growth rates may be tumor independent. We predict that
      effective antiangiogenic therapies will block a tumor's ability to augment
      angiogenesis initiation rather than subsequent neovessel growth.

PMID- 9288161
TI  - 12,13-isotaxanes: synthesis of new potent analogs and X-ray crystallographic
      confirmation of structure.

PMID- 9288163
TI  - Terbenzimidazoles: influence of 2"-, 4-, and 5-substituents on cytotoxicity and
      relative potency as topoisomerase I poisons.
AB  - Terbenzimidazoles poison the nuclear enzyme topoisomerase I and possess
      significant cytotoxic activity against several human tumor cell lines. The
      relative pharmacological activity of 4,5- and 5,6-benzoterbenzimidazoles was
      compared to that of 5-phenylterbenzimidazole (3). 5,6-Benzoterbenzimidazole is
      inactive as a topoisomerase I poison and did not exhibit significant cytotoxic
      activity. In contrast, 4,5-benzoterbenzimidazole retained activity as a
      topoisomerase I poison but exhibited weak cytotoxic activity relative to 3. While
      5-(1-naphthyl)terbenzimidazole is less potent than 3 as a topoisomerase I poison
      and cytotoxic agent, 5-(2-naphthyl)-terbenzimidazole has comparable activity to
      3. The presence of a p-methoxy or p-chloro substituent on the phenyl moiety did
      not dramatically alter the pharmacological activity of 3. Several analogs of 3
      were synthesized wherein the 2"-substituent varied from methyl, ethyl, propyl,
      isopropyl, phenyl to p-methoxyphenyl. Evaluation of the intrinsic activity of
      these analogs as topoisomerase I poisons indicates that topoisomerase I poisoning
      was not diminished by the presence of a methyl, ethyl, propyl, and isopropyl
      substituent at the 2"-position. Among the various 2"-substituted analogs
      evaluated, only in the case of 2"-(p-methoxyphenyl)-5-phenylterbenzimidazole was
      a significant decrease in cytotoxicity observed.

PMID- 9288162
TI  - Selective inhibition of neuronal nitric oxide synthase by N omega-nitroarginine
      and phenylalanine-containing dipeptides and dipeptide esters.
AB  - A series of N omega-nitroarginine (ArgNO2)- and phenylalanine-containing
      dipeptides and dipeptide esters were synthesized as potential selective
      inhibitors of neuronal nitric oxide synthase (nNOS). All of the dipeptides and
      dipeptide esters are competitive inhibitors of nNOS, macrophage nitric oxide
      synthase (iNOS), and endothelial nitric oxide synthase (eNOS), except for the
      ones that contain D-ArgNO2 (8-10, 12, 13), which are uncompetitive inhibitors of
      iNOS but competitive inhibitors of nNOS and eNOS. None of the dipeptides or
      dipeptide esters tested (1, 2, 12, 13) exhibited time-dependent inhibition of any
      of the NOS isoforms, unlike N omega-nitro-L-arginine itself, which does, although
      it is reversible. The order of the amino acids in the dipeptide or dipeptide
      ester is important to selectivity, and the selectivity depends on the chirality
      of the amino acids. In the case of the corresponding benzyl esters (5 vs 6), both
      dipeptides favor iNOS over nNOS and eNOS inhibition. All of the dipeptide methyl
      esters containing a D-amino acid, however, exhibit an inhibitory preference for
      nNOS over iNOS and eNOS. The most impressive selectivities observed are 1800- and
      800-fold for 12 and 13, respectively, in favor of nNOS over iNOS; unfortunately,
      the selectivities of these compounds for nNOS over eNOS are only 2.5 and 5.3,
      respectively.

PMID- 9288164
TI  - Synthesis of carboranes containing an azulene framework and in vitro evaluation
      as boron carriers.
AB  - 3-(o-Carboranylhydroxymethyl)-7-isopropylazulene sodium carboxylate (1) and 3-(o
      carboranylmethyl)-7-isopropylazulene sodium sulfonate (2) were synthesized from
      the palladium-catalyzed addition reaction of 1-carboranyltributylstannane (4) to
      azulene aldehydes (3 and 9). Although the water solubility of 1 was of the order
      of 10(-6) M, that of 2 was of the order of 10(-3) M and was enough for clinical
      use. The cytotoxicity of 1 (IC50) toward B-16 melanoma cells was of the order of
      10(-5) M, whereas that of 2 was of the order of 10(-4) M. This value was close to
      that of BPA (approximately 9 x 10(-3) M) which is utilized for clinical use. The
      boron uptake by B-16 cells was 0.17 microgram of B/10(6) cells for 1 and 0.25
      microgram of B/10(6) cells for 2. It is clear that compound 2 accumulates in B-16
      melanoma cells with a significantly high level although it is highly water
      soluble and its cytotoxicity is significantly low.

PMID- 9288165
TI  - Heteroaryl analogues of AMPA. Synthesis and quantitative structure-activity
      relationships.
AB  - A number of 3-isoxazolol bioisosteres, 7a-i, of (S)-glutamic acid (Glu), in which
      the methyl group of (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic
      acid (AMPA, 1) was replaced by different 5-membered heterocyclic rings, were
      synthesized. Comparative in vitro pharmacological studies on this series of AMPA
      analogues were performed using receptor binding assays (IC50 values) and the
      electrophysiological rat cortical slice model (EC50 values). None of these
      compounds showed detectable affinity for the N-methyl-D-aspartic acid subtype of
      Glu receptors. Some of the compounds were weak inhibitors of [3H]kainic acid
      binding. The inhibitory effects on [3H]AMPA binding and agonist potencies at AMPA
      receptors of 7a-i were strictly dependent on the structure, electrostatic
      potential, and methyl substitution of the heterocyclic 5-substituent. Thus, while
      7a (IC50 = 0.094 microM; EC50 = 2.3 microM) was approximately equipotent with
      AMPA (IC50 = 0.023 microM; EC50 = 5.4 microM), (RS)-2-amino-3-[3-hydroxy-5-(1H
      imidazol-2-yl)isoxazol-4-yl]propio nic acid (7b) (IC50 = 48 microM; EC50 = 550
      microM) was some 2 orders of magnitude weaker than AMPA, and (RS)-2-amino-3-[3
      hydroxy-5-(1-methyl-1H-imidazol-2-yl)-isoxazol-4 -yl] propionic acid (7c) (IC50 >
      100 microM; EC50 > 1000 microM) was inactive. Furthermore, (RS)-2-amino-3-[3
      hydroxy-5-(2-methyl-2H-tetrazol-5-yl)isoxazol -4-yl] propionic acid (7i) (IC50 =
      0.030 microM; EC50 = 0.92 microM) was more potent than AMPA, whereas its N-1
      methyl isomer, (RS)-2-amino-3-[3-hydroxy-5-(1-methyl-1H-tetrazol-5-yl)isoxazol -4
      yl] propionic acid (7h) (IC50 = 54 microM; EC50 > 1000 microM) was inactive as an
      AMPA agonist. A quantitative structure-activity relationship (QSAR) analysis
      revealed a positive correlation between receptor affinity, electrostatic
      potential near the nitrogen atom at the "ortho" position of the heterocyclic 5
      substituent, and the rotational energy barrier around the bond connecting the two
      rings. We envisage that a hydrogen bond between the protonated amino group and an
      ortho-positioned heteroatom of the ring substituent at the 5-position stabilize
      receptor-active conformations of these AMPA analogues.

PMID- 9288167
TI  - Novel biological response modifiers: phthalimides with tumor necrosis factor
      alpha production-regulating activity.
AB  - Novel N-substituted phthalimides (2-substituted 1H-isoindole-1,3-diones) were
      prepared, and their effects on tumor necrosis factor-alpha (TNF-alpha) production
      by human leukemia cell line HL-60 stimulated with 12-O-tetradecanoylphorbol 13
      acetate (TPA) or okadaic acid (OA) were examined. A structure-activity
      relationship study of the N-phenylphthalimides and N-benzylphthalimides revealed
      that their enhancing effect on TPA-induced TNF-alpha production by HL-60 cells
      and their inhibiting effect on OA-induced TNF-alpha production by HL-60 cells are
      only partially correlated.

PMID- 9288166
TI  - Use of conformationally restricted benzamidines as arginine surrogates in the
      design of platelet GPIIb-IIIa receptor antagonists.
AB  - The use of 5,6-bicyclic amidines as arginine surrogates in the design of a novel
      class of potent platelet glycoprotein IIb-IIIa receptor (GPIIb-IIIa) antagonists
      is described. The additional conformational restriction offered by the bicyclic
      nucleus results in 20-400-fold increases in potency compared to the freely
      flexible, acyclic benzamidine counterpart. The design, synthesis, structure
      activity relationships (SAR), and in vitro activity of this novel class of GPIIb
      IIIa antagonists are presented.

PMID- 9288168
TI  - Substituted (pyridylmethoxy)naphthalenes as potent and orally active 5
      lipoxygenase inhibitors; synthesis, biological profile, and pharmacokinetics of L
      739,010.
AB  - Dioxabicyclooctanyl naphthalenenitriles have been reported as a class of potent
      and nonredox 5-lipoxygenase (5-LO) inhibitors. These bicyclo derivatives were
      shown to be metabolically more stable than their tetrahydropyranyl counterparts
      but were not well orally absorbed. Replacement of the phenyl ring in the
      naphthalenenitrile 1 by a pyridine ring leads to the potent and orally absorbed
      inhibitor 3g (L-739,010, 2-cyano-4-(3-furyl)-7-[[6-[3-(3-hydroxy-6,8
      dioxabicyclo[3.2.1] octanyl)]-2-pyridyl]methoxy]naphthalene). Compound 3g
      inhibits 5-HPETE production by human 5-LO and LTB4 biosynthesis by human PMN
      leukocytes and human whole blood (IC50S of 20, 1.6, and 42 nM, respectively).
      Derivative 3g is orally active in the rat pleurisy model (inhibition of LTB4,
      ED50 = 0.3 mg/kg) and in the anesthetized dog model (inhibition of ex vivo whole
      blood LTB4 and urinary LTE4, ED50 = 0.45 and 0.23 microgram/kg/min, respectively,
      i.v. infusion). In addition, 3g shows excellent functional activity against
      ovalbumin-induced dyspnea in rats (60% inhibition at 0.5 mg/kg, 4 h pretreatment)
      and Ascaris-induced bronchoconstriction in conscious sheep (50% and > 85%
      inhibition in early and late phases, respectively at 2.5 micrograms/kg/min, i.v.
      infusion) and, more particularly in the conscious antigen sensitive squirrel
      monkey model (53% inhibition of the increase in RL and 76% in the decrease of
      Cdyn, at 0.1 mg/kg, po). In rats and dogs, 3g presents excellent pharmacokinetics
      (estimated half-lives of 5 and 16 h, respectively) and bioavailabilities (26% and
      73% when dosed as its hydrochloride salt at doses of 20 and 10 mg/kg,
      respectively, in methocel suspension). Based on its overall biological profile,
      compound 3g has been selected for preclinical animal toxicity studies.

PMID- 9288169
TI  - Design of low molecular weight hematoregulatory agents from the structure
      activity relationship of a dimeric pentapeptide.
AB  - We report herein, a new class of simple hematoregulatory semipeptides, formally
      derived from the cystine-dimerized peptide pGlu-Glu-Asp-Cys-Lys-OH, where the
      disulfide bond has been replaced by an isosteric dicarba bridge. The structure
      activity relationship (SAR) of a series of analogues incorporating replacements
      at positions 1 and 2 of peptide 1 led to the design of active conformationally
      constrained cyclic peptides (12, 13). Ring closure was achieved by cyclization of
      the N-terminal amino groups at position 2 of peptide 2 using pyrazine-2,3
      dicarboxylic acid. Subsequent excision of the putative C-terminal scaffold domain
      from the active cyclic peptides resulted in the discovery of a new class of low
      molecular weight hematoregulatory agents exemplified by compound 16. This
      semipeptide analogue, comprising two D-Ser residues connected via amide bonds to
      the acid groups of pyrazine-2,3-dicarboxylic acid, had comparable biological
      activity to the lead peptide 1. The stereochemical requirements for the observed
      biological activity of these novel compounds were examined. Furthermore, the
      hematopoietic synergistic activity induced by compound 16 in stromal cell
      cultures was blocked by an antibody known to neutralize the hematoregulatory
      effect of 1, indicating a common mechanistic end point. Compounds of the class
      typified by 16 may form the basis for the development of novel therapeutic agents
      within the area of immunoregulation.

PMID- 9288170
TI  - Synthesis and activity of 6-substituted purine linker amino acid
      immunostimulants.
AB  - A series of 6-substituted purinyl alkoxycarbonyl amino acids were synthesized and
      evaluated for their ability to stimulate cytotoxic T lymphocytes (CTLs) and the
      mixed lymphocyte reaction (MLR). A few of these compounds, in particular [[5-[6
      (N,N-dimethylamino)purin-9-yl]pentoxy]-carbonyl]D-arginine (BCH-1393, 4a),
      displayed an in vitro stimulation of CTLs comparable to interleukin 2 (IL 2). BCH
      1393 increased the CTL response between 10(-9) M and 10(-5) M. Further, this
      potent in vitro activity was reflected as a significant increase in CTL cell
      number in vivo. However, immunophenotyping of some of the other equipotent
      compounds did not reveal a parallel relative increase in CTLs in vivo. It was
      difficult to formulate a rigorous structure-activity relationship based on in
      vitro CTL activity. Nevertheless, the activity was dependent upon the nature of
      the 6-substituent on the purine, the type and stereochemistry of the amino acid,
      and the distance and spatial freedom between the purine and amino acid as defined
      by the length and rigidity of the linker. These compounds were generally
      nontoxic, as exemplified by BCH-1393. BCH-1393 is a promising immunostimulant
      which may be targeted for those disease states which require an increased CTL or
      TH1 type response.

PMID- 9288171
TI  - Total syntheses and anticholinesterase activities of (3aS)-N(8)-norphysostigmine,
      (3aS)-N(8)-norphenserine, their antipodal isomers, and other N(8)-substituted
      analogues.
AB  - N(8)-Benzylesermethole (6) was prepared from 5-methoxytryptamine (1) in five
      steps. Resolution of compound 6 by dibenzoyl- and ditoluyltartaric acid provided
      enantiomers (-)- and (+)-7. After demethylation, reaction with isocyanates and
      catalytic debenzylation over hydrogen, the total syntheses of (-)- and (+)-N(8)
      norphysostigmine [(-)- and (+)-11] and (-)- and (+)-N(8)-norphenserine [(-)- and
      (+)-12] were accomplished, (-)-N(8)-Norphysostigmine [(-)-11] and (-)-N(8)
      norphenserine [(-)-12] were also obtained by transformations of natural
      physostigmine [(-)-13] and phenserine [(-)-14] prepared from (-)-13. The absolute
      configurations and optical purity of compounds (-)-11, (-)-12, (+)-11, and (+)-12
      were confirmed by a comparison of their optical rotations with those of the
      compounds synthesized from physostigmine [(-)-13]. The anticholinesterase
      activities of N(8)-nor- and N(8)-substituted analogues, (-)- and (+)-9, -10, -11,
      -12, 15, and 16, were compared with those of physostigmine [(-)- and (+)-13] and
      phenserine [(-)- and (+)-14] and are reported.

PMID- 9288172
TI  - O6-(alkyl/aralkyl)guanosine and 2'-deoxyguanosine derivatives: synthesis and
      ability to enhance chloroethylnitrosourea antitumor action.
AB  - A series of O6-(alkyl/aralkyl)guanosines and 2'-deoxyguanosine analogs extended
      to peracetyl and N2-acetyl derivatives, potentially water soluble, was
      synthesized. Each was associated with N'-(2-chloroethyl)-N-[2
      (methylsulfonyl)ethyl]-N'-nitrosourea for in vitro evaluation on M4Beu melanoma
      cells of their ability to enhance the cytotoxic effect of this
      chloroethylnitrosourea, which is frequently reduced by repairs performed by O6
      alkylguanine-DNA-alkyltransferase. Structure-activity analysis revealed that (i)
      benzyl and 4-halobenzyl are the O6-substituents required to afford a significant
      activity, (ii) 2'-deoxyguanosine derivatives demonstrate greater potency than
      guanosine analogs, (iii) acetylation, especially at the N2 position, generally
      results in compounds with moderate ability but may prevent incorporation of such
      nucleosides into DNA. Accordingly, O6-(4-iodobenzyl)-N2-acetylguanosine (3b) and
      O6-benzylperacetyl-2'-deoxyguanosine (2a), as well as O6-benzyl-N2
      acetylguanosine (1b) and O6-benzyl-N2-acetyl-2'-deoxyguanosine (2b), by far the
      most water soluble, exhibit a good profile for further in vivo trials by the
      intravenous route.

PMID- 9288173
TI  - Mapping the peripheral benzodiazepine receptor binding site by conformationally
      restrained derivatives of 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-
      isoquinolinecarboxamide (PK11195).
AB  - A synthetic-computational approach to the study of the binding site of peripheral
      benzodiazepine receptor (PBR) ligands related to 1-(2-chlorophenyl)-N-methyl-N-(1
      methylpropyl)-3-isoquinolinecarboxam ide (PK11195, 1) within their receptor has
      been developed. A wide series of conformationally restrained derivatives of 1 has
      been designed with the aim of probing the PBR binding site systematically. The
      synthesis of these compounds involves palladium-catalyzed coupling and amidation
      as the key steps. Twenty-nine rigid and semirigid derivatives of 1 were tested in
      binding studies using [3H]-1, and most of these showed PBR affinities in the
      nanomolar range. The essential role of the carbonyl moiety as a primary
      pharmacophoric element in the recognition by and the binding to PBR has been
      confirmed, and the restricted range of the carbonyl orientations, which
      characterizes the most potent ligands, points to a specific hydrogen-bonding
      interaction, mainly directed by the geometrical factors, when the electronic ones
      are fulfilled. Moreover, the fundamental importance of the short-range dispersive
      interactions in the modulation of the binding affinity and, hence, in the
      stabilization of the ligand-receptor complex, emerged from the QSAR models
      reported.

PMID- 9288174
TI  - Synthesis and structure-activity relationships of 6,7-benzomorphan derivatives as
      antagonists of the NMDA receptor-channel complex.
AB  - We have synthesized a series of stereoisomeric 6,7-benzomorphan derivatives with
      modified N-substituents and determined their ability to antagonize the N-methyl-D
      aspartate (NMDA) receptor-channel complex in vitro and in vivo. The ability of
      the compounds to displace [3H]-MK-801 from the channel site of the NMDA receptor
      in rat brain synaptosomal membranes and to inhibit NMDA-induced lethality in mice
      was compared with their ability to bind to the mu opioid receptor. Examination of
      structure-activity relationships showed that the absolute stereochemistry is
      critically important for differentiating these two effects. (-)-1R,9 beta,2"S
      enantiomers exhibited a higher affinity for the NMDA receptor-channel complex
      than for the mu opioid receptor. The aromatic hydroxy function was also found to
      influence the specificity of the compounds. Shift of the hydroxy group from the
      2'-position to the 3'-position significantly increased the affinity for the NMDA
      receptor-channel complex and considerably reduced the affinity for the mu opioid
      receptor. From this series of 6,7-benzomorphan derivatives, the compound 15cr.HCl
      [(2R)-[2 alpha, 3(R*),6 alpha]-1,2,3,4,5,6-hexahydro-3-(2-methoxypropyl)-6,11,11
      trimethyl -2,6-methano-3-benzazocin-9-ol hydrochloride] was chosen as the optimum
      candidate for further pharmacological investigations.

PMID- 9288175
TI  - (S)-spiro[(1,3-diazacyclopent-1-ene)-5,2'-(7'-methyl-1',2',3',4'-
      tetrahydronaphthalene)]: resolution, stereospecific synthesis, and preliminary
      pharmacological characterization as a partial alpha-adrenergic agonist.
AB  - Recently, we reported on the design, synthesis, and structure-activity
      relationships of a series of spiroimidazolines endowed with alpha-adrenergic
      agonist activities. Among the compounds described, (R,S)-spiro(1,3-diazacyclopent
      1-ene)-[5,2'](7'-methyl-1'2',3', 4',-tetrahydronaphthalene) fumarate (5RS) was
      chosen for further development as a venotonic agent. The resolution of this
      compound, as well as the pharmacological characterization of the enantiomers,
      stereospecific synthesis of eutomer (5S, S 18149), and determination of absolute
      configuration by single-crystal X-ray diffraction analysis, are described.

PMID- 9288177
TI  - Synthesis and pharmacological activity of deltorphin and dermorphin-related
      glycopeptides.
AB  - The solid phase procedure, based on the Fmoc chemistry, was used to prepare some
      opioid deltorphin (H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2, DEL C) and dermorphin (H
      Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2, DER) analogues in which a D-glucopyranosyl
      moiety is beta-O-glycosidically linked to a Thr4 or Thr7 side chain. Their
      activities were determined in binding studies based on displacement of mu- and
      delta-receptor selective radiolabels from rat brain membrane synaptosomes, in
      guinea pig ileum and rabbit jejenum bioassays, and, in vivo, by a mouse tail
      flick test after intracerebroventricular (icv) and subcutaneous (sc)
      administrations. The glyco analogues modified at position 4 displayed low opioid
      properties, while Thr7-glycosylated peptides retained high delta- or mu
      selectivity and remarkable activity in vivo. In particular, as systemic
      antinociceptive agents, the latter glucoside-bearing compounds were more potent
      than the parent unglycosylated peptide counterparts, showing a high blood to
      brain rate of influx which may be due to the glucose transporter GLUT-1.

PMID- 9288176
TI  - Probes for narcotic receptor-mediated phenomena. 25. Synthesis and evaluation of
      N-alkyl-substituted (alpha-piperazinylbenzyl)benzamides as novel, highly
      selective delta opioid receptor agonists.
AB  - A series of N-alkyl- and N,N-dialkyl-4-[alpha-[(2S,5R)-4-allyl-2,5-dimethyl-1
      piperazinyl] benzyl]-benzamides were synthesized and evaluated for binding
      affinities at mu, delta, and kappa opioid receptor subtypes. Several compounds
      (2e,f,h,i,m) strongly bound to the delta receptor with IC50 values in the
      nanomolar range. On the other hand, the binding affinities of these compounds for
      the mu and kappa receptors were in the micromolar or greater range indicating
      excellent delta opioid receptor subtype selectivities. In this series, two
      important structure-activity relationships were found for the delta receptor
      binding affinity. First, the spatial orientation of the alpha-benzylic position
      influenced the affinities with the alpha R derivatives 2a-n generally showing
      more than 10-fold greater affinity than the alpha S derivatives 3a-n. Second, the
      binding affinities were strongly influenced by the number of alkyl substituents
      on the amide nitrogen. N-Monoalkylbenzamide derivatives 2b-d showed lower
      affinity than N,N-dialkylbenzamide derivatives 2e-n, and the N-unsubstituted
      benzamide derivative 2a had the lowest affinity for the delta receptor in the
      series. The dramatic effect of the amide group substitution pattern on the
      binding affinity for the delta receptor strongly suggests that the amide function
      is an important structural element in the interaction of this series of compounds
      at the delta receptor. Selective compounds in this series were examined for
      binding affinity in cloned human mu and delta receptors. The results obtained
      generally paralleled those from the rat brain binding assay. Compounds 2e,f with
      potent delta binding affinities and high delta selectivities were shown to be
      delta agonists with high selectivity by studies in the guinea pig ileum (GPI) and
      mouse vas deferens (MVD) preparations. Compound 2f was the most selective
      compound in the rat brain and GPI/MVD assays with 1755- and 958-fold delta vs mu
      selectivity, respectively.

PMID- 9288178
TI  - A theoretical investigation of tight-binding thermolysin inhibitors.
AB  - A tight-binding thermolysin inhibitor, Cbz-Phe-psi[PO2NH]-Leu-Ala (ZFpLA, Ki =
      0.068 nM), and its analogs, ZRp(O)LA (R = Ala, Leu or Phe) have been studied
      using the finite difference solution to the linearized Poisson-Boltzmann equation
      (FDPB) and solvation entropy correction (SEC). The binding energy difference
      between conformationally different thermolysin inhibitors ZFpLA and ZGpLL is
      estimated using three approaches. Two of approaches use the X-ray structures of
      ZFpLA-thermolysin and ZGpLL-thermolysin structures. The third one uses both X-ray
      structures to calculate binding energy differences from ZFpLA and ZGpLL to a
      hypothetical intermediate MepLA. All the results are qualitatively correct with
      one closely reproducing the experimental value. The enhancement of the ZFpLA
      binding is attributed largely to the solvation entropy or "hydrophobic force".
      The binding mode of the ZGpLR N-terminal moiety appears to be electrostatically
      unfavorable. Reducing the polarity of that moiety is predicted to enhance binding
      affinity. The binding trends due to the hydrophobic variation of ZRp(O)LA are
      calculated within 1 kcal/mol of the experimental values. Increasing lipophilicity
      of a ligand favors the binding due to the difference of surface area change
      between the free state and the bound state. The analysis of energetic components
      shows that these trends are not specific for the binding of phosphorus-containing
      inhibitors but are generally true for protein-ligand interactions. The
      electrostatic calculation does not support the involvement of the second
      protonation of ZFpLA in binding. Therefore, reexamining the second protonation of
      ZFpLA or seeking further experimental support seems appropriate. The structural
      sensitivity of the FDPB calculation was assessed by using ligand and receptor
      structures from different X-ray studies of thermolysin. The small deviations (<
      0.3 A) in the receptor structures do not cause significant changes in
      electrostatic binding energy if there is no structural change in modified
      regions.

PMID- 9288179
TI  - Synthesis and properties of second-generation 2-5A-antisense chimeras with
      enhanced resistance to exonucleases.
AB  - In order to stabilize 2-5A-antisense chimeras to exonucleases, we have
      synthesized chimeric oligonucleotides in which the last phosphodiester bond at
      the 3'-terminus of the antisense domain was inverted from the usual 3',5'-linkage
      to a 3',3'-linkage. The preparation of such analogues was accomplished through
      standard phosphoramidite chemistry with the use of a controlled pore glass solid
      support with a nucleoside attached through its 5'-hydroxyl, thereby permitting
      elongation at the 3'-hydroxyl. The structures of such terminally inverted linkage
      chimeras of the general formula pA4-[pBu]2-(pdNn3'-3'dN) were corroborated by a
      combination of snake venom phosphodiesterase digestion in the presence or absence
      of bacterial alkaline phosphatase. Most characteristically, the presence of the
      3'-terminal-inverted phosphodiester linkage produced an unnatural dinucleotide of
      general composition dN3'p3'dM. These structures could be confirmed by independent
      synthesis and fast atom bombardment mass spectroscopy (FAB). 2-5A-Antisense
      chimeras of this structural class, pA4-[pBu]2-(pdNn'3-3'dN), were 5-6-fold more
      stable than their unmodified congeners, pA4-[pBu]2-(pdN)n, to degradation by a
      representative phosphodiesterase from snake venom. In 10% human serum, the new 2
      5A-antisense chimeras, pA4-[pBu]2-(pdNn3'-3'dN), possessed a half-life that was
      28-fold longer than that of the unmodified chimeras. These results provide entry
      to a second generation of 2-5A-antisense chimeras.

PMID- 9288180
TI  - Expression of antioxidant enzymes in human prostatic adenocarcinoma.
AB  - BACKGROUND: Antioxidant enzymes (AEs), which catalyze the conversion of reactive
      oxygen species (ROS) to water, include catalase (CAT), manganese-containing
      superoxide dismutase (MnSOD), and copper and zinc-containing superoxide dismutase
      (CuZnSOD). Previous work has indicated that MnSOD, CAT, and CuZnSOD levels are
      nearly always low in cancer cells. METHODS: Formalin-fixed, paraffin-embedded
      tissue from 31 radical prostatectomy specimens was immunohistochemically stained
      with polyclonal antibodies to CAT, MnSOD, and CuZnSOD. RESULTS: Malignant glands
      are typically stained with less intensity than benign/ hyperplastic glands.
      Marked heterogeneity of staining intensity was seen in the malignant glands for
      each of the three enzymes. A similar, though less marked, spectrum of
      heterogeneity of staining intensity was observed in the benign/hyperplastic
      epithelium contained in the specimens. No statistically significant correlation
      was found between intensity of staining for any of the three antioxidant enzymes
      and Gleason score, tumor stage, or preoperative prostate-specific antigen (PSA).
      CONCLUSIONS: Cellular levels of CAT, MnSOD, and CuZnSOD in prostatic
      adenocarcinoma reveal that many tumors appear to have decreased levels of
      expression. The finding that malignant prostate epithelium may have lowered
      expression of AEs suggests that further study of the role of AEs in malignant
      transformation in the prostate is warranted.

PMID- 9288181
TI  - Epidermal growth factor-related peptides in human prostatic fluid: sources of
      variability in assay results.
AB  - BACKGROUND: Prostatic fluid (PF) provides a unique medium for noninvasive
      evaluation of critical growth and differentiation signals in the prostatic
      microenvironment. The purpose of this study was to establish the feasibility of
      measuring two prostatic mitogens, epidermal growth factor (EGF) and transforming
      growth factor-alpha (TGF-alpha) in PF, and specifically to quantify extraneous
      variability attributable to the assay itself, sample handling, or biological
      variation within an individual over time. METHODS: PF was collected by
      transrectal massage from consecutive patients attending a urology clinic. Pooled
      PF and individual samples from 25 men with stable benign prostatic hyperplasia
      (BPH) were analyzed for EGF and TGF-alpha by radioimmunoassay and for total
      protein. RESULTS: Reproducibility was adequate at dilutions as low as 1:50 (2
      microliter pooled sample) and 1:5 (20 microliters) for EGF and TGF-alpha,
      respectively. Results were not affected by freeze-thaw cycles, time in storage,
      or protease inhibition in fresh PF. EGF and TGF-alpha were detectable in 100% and
      92% of individual men, with respective means of 152 and 0.2 ng/ml. Correlations
      between two samples obtained from the same man within 12 months were highly
      significant (EGF r = 0.89, TGF-alpha r = 0.71). Protein concentrations were
      consistent over time; expression of either peptide per weight of protein rather
      than per volume did not improve within-man correlation. Between-man variability
      far exceeded within-man variability for both peptides, and was estimated to
      account for 84% and 61% of the total variability in EGF and TGF-alpha,
      respectively. There was no correlation between EGF and TGF-alpha in the same
      samples. CONCLUSIONS: We conclude that men with BPH secrete consistent and
      distinct levels of EGF-related peptides in PF, and that these levels can be
      detected with acceptable sensitivity and precision by radioimmunoassay (RIA).
      Measurement of TGF-alpha, which has not been reported previously, requires a
      relatively larger sample.

PMID- 9288182
TI  - Metastatic prostatic adenocarcinoma presenting as a pituitary mass: shrinkage of
      the lesion and clinical improvement with medical treatment.
AB  - BACKGROUND: Metastatic involvement of the pituitary gland is a very unusual
      presentation of prostatic cancer. We report a favorable response to medical
      treatment in such a patient. METHODS AND RESULTS: A 77-year-old man presented
      with blindness, ophthalmoplegia in his left eye, and mild impairment of memory
      and mental status. Neuroradiological studies showed a huge intra- and suprasellar
      lesion that destroyed the sellar floor and extended into the sphenoid sinus.
      Transsphenoidal biopsy of the lesion demonstrated a prostatic adenocarcinoma.
      Postoperative studies revealed an enlarged prostate gland and multiple lytic bone
      lesions. The patient was treated with a combination of leuprolide acetate plus
      flutamide. Four months later, the patient exhibited a marked improvement in his
      neurologic status and regained vision in the right eye (visual acuity 6/20).
      Repeat magnetic resonance imaging of the sellar region confirmed a striking
      shrinkage of the prostatic metastasis. The clinical status remained stable for 22
      months, after which time the disease progressed and the patient died 25 months
      after beginning treatment. CONCLUSIONS: A favorable response to combined androgen
      blockade suggests that medical therapy should be considered the therapy of first
      choice when surgical removal of the metastatic lesion in the pituitary is
      impossible or too risky.

PMID- 9288183
TI  - Development of a hammerhead ribozyme against bcl-2. I. Preliminary evaluation of
      a potential gene therapeutic agent for hormone-refractory human prostate cancer.
AB  - BACKGROUND: The bcl-2 oncoprotein suppresses apoptosis and, when overexpressed in
      prostate cancer cells, makes these cells resistant to a variety of therapeutic
      agents, including hormonal ablation. Therefore, bcl-2 provides a strategic target
      for the development of gene knockout therapies to treat human prostate cancers.
      Towards this end, we have synthesized an anti-bcl-2 gene therapeutic reagent
      based on ribozyme technology and have tested its effectiveness against bcl-2 mRNA
      in vitro and in vivo. METHODS: A divalent hammerhead ribozyme was constructed by
      recombining two catalytic RNA domains into an antisense segment of the coding
      region for human bcl-2 mRNA. A disabled ribozyme lacking catalytic activity was
      also constructed as a control reagent for our experiments. The ribozymes were
      tested for endonucleolytic activity against synthetic and natural bcl-2 mRNAs.
      Simple transfection procedures were then utilized to introduce the ribozymes into
      cultured prostate cancer cells (LNCaP derivatives). We measured the effects of
      the ribozymes on endogenous expression of bcl-2 mRNA and protein in these cells
      as well as their ability to induce apoptosis. RESULTS: The functional but not the
      disabled ribozyme was able to rapidly degrade bcl-2 mRNA in vitro, without the
      requirement for any other cellular protein or factor. When directly transfected
      into LNCaP cell variants, it significantly reduced bcl-2 mRNA and protein levels
      within 18 hr of treatment. This activity was sufficient to induce apoptosis in a
      low-bcl-2-expressing variant of LNCaP, but not in a high-bcl-2-expressing LNCaP
      line. For the high-bcl-2-expressing variant, however, it did restore the ability
      to genetically respond to a secondary apoptotic agent, phorbol ester, as
      evidenced by the renewed ability of phorbol ester to induce NGF1A mRNA in these
      cells. CONCLUSIONS: This study supports the potential utility of an anti-bcl-2
      ribozyme reagent for reducing or eliminating bcl-2 expression from hormone
      refractory prostate cancer cells and for killing prostate cancer cells. As such,
      it is the first step toward an effective gene therapy against hormone-refractory
      human prostate cancers.

PMID- 9288184
TI  - Effects of a new 5 alpha reductase inhibitor (epristeride) on human prostate cell
      cultures.
AB  - BACKGROUND: Inhibitors of 5 alpha reductase (5 alpha R), the enzyme that converts
      testosterone to dihydrotestosterone (DHT), have been shown to retard the growth
      of hyperplastic prostates. This study evaluates the effects of the 5 alpha R
      inhibitor, epristeride, on cultured stromal and epithelial cells from benign,
      hyperplastic adult prostates. METHODS: [3H]-thymidine incorporation was used as a
      measure of proliferation. Prostate-specific antigen (PSA) was quantified by ELISA
      and reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Stromal
      cell proliferation in response to testosterone was dose-dependently inhibited by
      epristeride (1 x 10(-9) -3 x 10(-7) M, P < 0.05). However, epristeride had no
      effect on DHT-induced growth or the growth of androgen-unresponsive stroma.
      Upregulation of PSA secretion from epithelial cells by androgens was
      downregulated by epristeride (3 x 10(-9) M, P < 0.05) in testosterone-treated
      cells. Transforming growth factor beta-1 (TGF beta-1) secretion was downregulated
      by testosterone treatment and increased following treatment with epristeride (3 x
      10(-9) M, P < 0.05). CONCLUSIONS: This demonstrates that epristeride specifically
      blocks testosterone-induced effects on prostatic cultures. TGF beta-1 may be a
      marker of 5 alpha reductase activity.

PMID- 9288185
TI  - Transient tyrosine phosphorylation of p34cdc2 is an early event in radiation
      induced apoptosis of prostate cancer cells.
AB  - BACKGROUND: Previous studies have demonstrated that androgen-independent human
      prostate cancer cells undergo radiation-induced apoptosis. The present study
      investigated the early events that trigger the apoptotic response of prostate
      cancer cells after exposure to ionizing irradiation. METHODS: Human prostate
      cancer cells (PC-3) were exposed to single doses of ionizing irradiation, and the
      immediate protein phosphorylation events were temporally correlated with
      induction of apoptosis. Apoptosis among the irradiated cell populations was
      evaluated using the fluorescein-terminal transferase assay. RESULTS: The kinetics
      of phosphorylation of a Mr 34,000 substrate followed a transient course: an
      initial increase was observed after 10 min postirradiation, reaching maximum
      levels by 60 min, and the protein subsequently underwent rapid dephosphorylation.
      Subsequent analysis revealed that the substrate for this tyrosine phosphorylation
      is the serine/ threonine p34cdc2 protein kinase, a cell cycle regulatory protein
      that controls cell entry into mitosis. This enhanced phosphorylation temporally
      preceded the radiation-induced apoptotic DNA fragmentation as detected by the
      terminal transferase technique. Arresting the cells in G0/G1 phase by
      pretreatment with suramin totally abrogated radiation-induced phosphorylation of
      p34cdc2 protein at the tyrosine residue, indicating that this posttranslational
      modification occurs in cell populations that escape G2 arrest and undergo
      apoptosis in response to radiation. CONCLUSIONS: These results suggest that a
      rapid and transient phosphorylation of a protein that controls mitotic
      progression precedes and potentially triggers radiation-induced apoptosis in
      prostate cancer cells.

PMID- 9288186
TI  - Follow-up evaluation of prostate cancer patients infused with autologous
      dendritic cells pulsed with PSMA peptides.
AB  - BACKGROUND: We recently conducted a phase I clinical trial administering
      autologous dendritic cells pulsed with prostate-specific membrane antigen (PSMA)
      peptides to advanced prostate cancer patients. Participants were divided into 5
      groups receiving 4 or 5 infusions of peptides alone (PSM-P1 or -P2; groups 1 and
      2, respectively), autologous DC (group 3), or DC pulsed with PSM-P1 or -P2
      (groups 4 and 5, respectively). Seven partial responders were observed. Follow-up
      evaluation of these responders is presented in this report. METHODS: Clinical
      monitoring for hematological studies and prostate markers was conducted up to 370
      days from the start of the phase I study. Data collected include: lymphocyte,
      hematocrit, alkaline phosphatase, prostate-specific antigen (PSA), free PSA, and
      PSMA levels. RESULTS: Groups 4 and 5 (patients infused with DC pulsed with PSM-P1
      or -P2) represented 5/7 responders. The length of response was between 100 days
      (1 patient) to 200 days or above (6 patients). Four patients still remained
      responsive at the end of the period of observation. CONCLUSIONS: The responses
      observed in this phase I clinical trial are significant and of long duration.
      Most of the responders were in treatment groups infused with DC pulsed with PSM
      P1 or -P2, suggesting the requirement of both components for effective
      immunotherapy.

PMID- 9288187
TI  - Transrectal ultrasound microbubble contrast angiography of the prostate.
AB  - BACKGROUND: Prostate cancer, suspected by serum prostate-specific antigen (PSA)
      elevation and/or digital abnormalities, is not always evident on gray-scale or
      color Doppler transrectal ultrasound (TRUS). EchoGen (Sonus Pharmaceuticals,
      Inc., Bothell, WA), a blood vessel image enhancer able to visualize smaller, low
      flow vessels and thus possibly the microvascular angiogenesis often associated
      with cancer, was employed to see if it would improve prostate cancer detection,
      particularly in patients with a rising serum PSA and prior negative biopsies.
      METHODS: Color Doppler TRUS was performed before and after intravenous injection
      of 0.05 ml/kg of EchoGen. Random and/or specifically directed sextant TRUS
      biopsies were performed. RESULTS: Fifteen patients with serum PSA elevations were
      included in the study. Fourteen had a negative prior biopsy (1-3 x). Prostate
      cancer was detected in 5 patients. Microvascular patterns were judged abnormal in
      8 patients, 2 of which proved malignant, 2 of which were benign, and 1 of which
      was diagnosed with prostatis. False-negative results were observed in 3 patients,
      whose positive biopsy sites were from the prostate apex. CONCLUSIONS: Following
      EchoGen administration, prostate blood vessel image enhancement was noted in all
      patients, and there were no adverse reactions during or after EchoGen
      administration with the dose employed.

PMID- 9288188
TI  - Target to apoptosis: a hopeful weapon for prostate cancer.
AB  - BACKGROUND: Prostate cancer is the most commonly diagnosed neoplasm and the
      second leading cause of male death in this country. Multiple genetic and
      epigenetic factors have been implicated in the oncogenesis and progression of
      prostate cancer. However, the molecular mechanisms underlying the disease remain
      largely unknown. The major difficulty in the clinical management of prostate
      cancer stems from the reality that reliable and accurate diagnostic/prognostic
      biomarkers are not available and that effective treatment regimens for hormone
      resistant prostate cancers are yet to be developed. METHODS: The present review,
      through extensive literature research, summarizes the most recently accumulated
      experimental and clinical data on the relationship between apoptosis and prostate
      cancer. We analyze the possibility of inducing prostate cancer cell apoptosis by:
      1) androgen ablation by castration or biochemical antagonists: 2)
      chemotherapeutic drugs or natural/synthetic chemicals; 3) manipulation of
      apoptosis-related oncoproteins; and 4) modulation of intracellular signal
      transducers. RESULTS: 1) Prostate cancer, like most other solid tumors,
      represents a very heterogeneous entity. Most prostate cancers, at the time of
      clinical diagnosis, present themselves as mixtures of androgen-dependent and
      androgen-independent cells. 2) Most prostate cancers respond initially to
      androgen ablation since the population of androgen-dependent cells undergoes
      rapid apoptosis upon androgen withdrawal. However, androgen ablation rarely cures
      patients, most of whom will experience recurrence due to takeover of the tumor
      mass by androgen-independent tumor cells as well as the emergence of apoptosis
      resistant clones as a result of further genetic alterations such as bcl-2
      amplification. 3) On the other hand, although androgen-independent prostate
      cancer cells do not undergo apoptosis upon androgen blocking, they do maintain
      the appropriate molecular machinery of apoptosis. Therefore, certain conventional
      chemotherapy drugs can eliminate androgen-independent cancer cells by inducing
      apoptosis. 4) However, most drugs used in chemotherapy induce apoptosis or
      mediate cytotoxicity only in proliferating cancer cells. Human prostate cancer
      cells demonstrate very slow growth kinetics. Thus, novel chemical/natural
      products need be identified to eradicate those nonproliferating cancer cells. In
      this regard, the angiogenesis inhibitor, linomide, and a plant extract, beta
      lapachone, demonstrate very promising apoptosis-inducing effects on prostate
      cancer cells in a proliferation-independent manner. 5) An alternative way to
      modulate the apoptotic response is by interfering with the expression levels of
      essential regulatory molecule of apoptosis. Bcl-2 and p53 represent two prime
      targets for such manipulations. 6) Finally, modulation of signal transduction
      pathways (e.g., intracellular Ca2+ levels, PKC activity) involved in apoptosis
      may also induce and/or enhance the apoptotic response of prostate cancer cells.
      CONCLUSIONS: Modulation of apoptotic response represents a novel mechanism-based
      approach which may help identify novel drugs and/or develop new therapeutic
      regimens for the treatment of prostate cancers.

PMID- 9288189
TI  - Hypertensive heart disease: quantitative evaluation of response to therapy with
      cine MR imaging.
AB  - RATIONALE AND OBJECTIVES: To assess the ability of cine magnetic resonance (MR)
      imaging to help detect and quantity changes in left ventricular parameters in
      patients receiving antihypertensive therapy. MATERIALS AND METHODS: After
      undergoing baseline cine MR imaging of the heart, 16 (12 men, four women)
      hypertensive patients participating in a prospective drug trial began isradipine
      therapy. Follow-up serial cine MR imaging was performed at 3 months and 6 months.
      Myocardial mass, end-systolic volume, end-diastolic volume, stroke volume, and
      ejection fraction were measured. Results from transaxially acquired three
      dimensional data sets and monoplanar imaging were compared. RESULTS: Three
      dimensional data showed reductions of 11% in end-systolic volume (P = .0051) and
      17% in end-diastolic volume (P = .0023). These changes were not detected with
      monoplanar imaging. Changes in myocardial mass, stroke volume, and ejection
      fraction were not statistically significant. CONCLUSION: Three-dimensional cine
      MR imaging can depict small yet statistically significant reductions in left
      ventricular volumes in response to antihypertensive therapy.

PMID- 9288190
TI  - Percutaneous implantation of non-small-cell lung carcinoma: technique and
      observations.
AB  - RATIONALE AND OBJECTIVES: The authors performed this study to determine whether
      intrathoracic inoculation of non-small-cell lung carcinoma with fluoroscopic
      guidance would provide for more accurate implantation. MATERIALS AND METHODS: A
      tumor cell inoculum (2 x 10(6) cells per 0.15 mL) was injected percutaneously
      under fluoroscopic guidance at the posterior midaxillary line in 22 athymic nude
      mice. The mice underwent imaging with a mammographic unit at 3, 5, and 8 weeks
      after implantation. The mice were sacrificed at 8 weeks, and autopsy was
      performed to determine tumor yield. RESULTS: The use of a percutaneous technique
      under fluoroscopic guidance greatly facilitated the accurate implantation of
      xenografts. Tumor growth was seen at radiography in 18 of the 22 (82%) mice at 8
      weeks. Necropsy revealed a 100% tumor yield. Histologic examination confirmed
      adenocarcinoma of the lung. The average number of tumors found in the lung
      parenchyma was 1.05 +/- 0.35; the average number of tumors found in the
      mediastinum was 0.59 +/- 0.67. The average tumor weight was 389 mg +/- 64.3. The
      average tumor size was 300 mm3 +/- 66.23. CONCLUSION: With fluoroscopic guidance,
      percutaneous implantation of tumor cells in athymic nude mice is simple and
      effective.

PMID- 9288191
TI  - Liver tumor ablation: real-time monitoring with dynamic CT.
AB  - RATIONALE AND OBJECTIVES: To determine whether incomplete contact of ethanol with
      tumor limits the success of percutaneous ethanol injection therapy. MATERIALS AND
      METHODS: Percutaneous ethanol injection was performed in seven normal New Zealand
      white rabbits and 18 rabbits with 1-3-cm liver tumors 10-14 days after
      percutaneous implantation of suspended tumor cells. A 3-5 mL dose of ethanol was
      injected at a rate of 0.2 mL/sec either into normal liver remote from large
      vessels or directly into tumor. During and immediately after injection, axial, 2
      mm-thick, contrast material-enhanced computed tomography scans were obtained at
      reach of three levels every 9 seconds. RESULTS: In normal animals, virtually all
      injected ethanol tracked to the hepatic capsule. As ethanol was injected into
      tumors, peripheral tracking, similar to that seen in normal livers, or
      extratumoral puddling was observed. Ethanol-tumor contact was incomplete in 16 of
      18 animals (89%). Histopathologic analysis showed incomplete tumor necrosis.
      CONCLUSION: In this model of hepatic carcinoma metastasis, the tumor failed to
      hold sufficient ethanol for successful ablation by means of percutaneous ethanol
      injection therapy.

PMID- 9288192
TI  - Efficacy and feasibility of breast shielding during abdominal fluoroscopic
      examinations.
AB  - RATIONALE AND OBJECTIVES: The purpose was to measure radiation exposure to the
      breasts during abdominal fluoroscopic examinations and evaluate the efficacy of
      breast shielding with a leaded vest. MATERIALS AND METHODS: Sixty-six women
      underwent routine abdominal fluoroscopic examinations. During the examinations
      one breast was covered with a leaded shield. Radiation doses to both breasts were
      measured with a thermoluminescent dosimeter. The amount of radiation at the skin
      of the shielded breast was then compared with that at the skin of the nonshielded
      breast. RESULTS: Radiation exposure to the breasts varied substantially with the
      type of examination being performed and with the individual patient. The average
      radiation level at the skin of the unshielded breast was 119 mR (range, 0-6,320
      mR), compared with 59.6 mR (range, 0-1,640 mR) at the shielded breast. The
      average reduction in radiation exposure was 50% with shielding. CONCLUSION:
      Although the average level of radiation exposure to the breast during abdominal
      fluoroscopic examinations is generally low, use of a leaded vest can further
      reduce radiation to the breast for different types of examinations.

PMID- 9288193
TI  - Smaller format, laser camera-generated images: acceptability and cost savings.
AB  - RATIONALE AND OBJECTIVES: To evaluate the use of laser-generated smaller images
      in neuroradiologic practice. MATERIALS AND METHODS: Computed tomographic (CT)
      scans of the heads of five subjects were obtained at bone and brain windows in
      three formats: 12:1 (12 images on a 35 x 43-cm film), 15:1 and 20:1. Two laser
      camera systems were used. Images were measured, physically separated, and
      reconstructed as a 35 x 43-cm ensemble; they were presented randomly to seven
      radiologists who assessed image size and interpretability. Observer preference
      was also noted. One camera system was evaluated for contrast and spatial
      resolution by a medical physicist. RESULTS: These were negligible differences in
      image area between the 15:1 and 20:1 formats. No discernible differences in
      quality were found among the three formats. The 12:1 images were preferred by the
      radiologists, but the 20:1 images were deemed acceptable. Annualized cost savings
      of 46.7%, or $46,650, were projected for adoption of the 20:1 image format for
      neuroradiologic CT and magnetic resonance imaging. CONCLUSION: No major
      differences were detected in image area between the 15:1 and the 20:1 image
      formats or in image quality among the three formats. Use of a smaller image
      format may result in substantial cost savings.

PMID- 9288194
TI  - Radiology conference room: planning and development.

PMID- 9288195
TI  - Diagnostic radiology in an integrated curriculum: experience from the United Arab
      Emirates.

PMID- 9288196
TI  - We regret to inform you.

PMID- 9288197
TI  - Assessment and staging of nasal polyposis.
AB  - This paper deals only with "simple" nasal polyposis which is almost always found
      in both cavities of the nose. A computer-based questionnaire will be described.
      Objective methods are described, i.e. rhinostereometry, acoustic rhinometry,
      rhinomanometry, and nasal peak flow, and their value in estimating changes of the
      size of nasal polyps discussed.

PMID- 9288198
TI  - Horizontal otolith-ocular responses to lateral translation in benign paroxysmal
      positional vertigo.
AB  - Benign paroxysmal positional vertigo (BPPV) is assumed to result from utricular
      damage, but it is controversial if patients have manifest utricular dysfunction.
      Therefore, we investigated linear vestibulo-ocular reflexes (LVORs) during
      lateral whole-body translation in 14 patients with unilateral BPPV. Patients were
      subjected to linear acceleration steps of 0.24 g along the interaural axis, which
      were applied randomly to the left and right, both in the dark and in the light
      with a visual target at a distance of 60 cm. The LVOR was measured by EOG from
      the slow phase velocity of the averaged and desaccaded compensatory eye movement.
      In normal cases, maximum asymmetry of LVOR velocity was 13% in the dark and 10%
      in the light. In patients, LVOR velocities were normal in the dark but mildly
      reduced in the light (p < 0.05). Five patients had mild LVOR asymmetries in the
      dark (range 18-38%) and two in the light (11 and 13%), but there was no
      consistent relationship to the affected side. The absence of gross changes of the
      LVOR may be explained either by minor utricular damage that is functionally
      irrelevant or by central compensation of a chronic unilateral deficit.

PMID- 9288199
TI  - Myogenic vestibular-evoked potentials in normal subjects: a comparison between
      responses obtained from sternomastoid and trapezius muscles.
AB  - Brief intense clicks cause short latency microcontraction of cervical muscles.
      Several studies have supported the hypothesis that these microcontractions are of
      vestibular origin. Averaging these muscular responses enables us to obtain
      myogenic vestibular evoked potential (MVEP). The receptor of these responses is
      thought to be the saccule, afferent pathways being the vestibular nerve and
      efferent pathways the vestibulospinal tract. However, discrepancies are reported
      with regard to results obtained in healthy subjects: some authors obtained
      symmetrical response to monaural clicks whereas others obtained responses of
      greater amplitude on the muscle ispilateral to stimulation. These discrepancies
      may be due to the presence of different recording sites (inion, sternomastoid or
      trapezius muscles). The aim of this study was to clarify MVEP results in healthy
      subjects, using a simple non-traumatic method, and to compare the results
      obtained on sternomastoid (SM) and trapezius muscles (TRP). Sixteen normal
      hearing healthy subjects were involved. Latencies and amplitude of both SM and
      TRP muscle were reproducible in the same subject. Patterns of response were
      similar to those obtained in previous studies. Following binaural and monaural
      stimulations, latencies of MVEP were symmetrical on both muscles and amplitudes
      tended to be greater on muscles contralateral to stimulation, which conflicts
      with previous results in the literature. Whatever the type of stimulation,
      latencies of responses obtained on SM were significantly shorter (mean = -3.8
      ms), and amplitudes lower (mean = -7.1 microV), than those obtained on TRP.
      Binaural stimulation resulted in responses of greater amplitude compared to
      monaural (mean = 0.45 microV). Given the intrasubject reproducibility of the
      responses, these methods allow MEVP to be recorded in a standardized and
      reproducible way.

PMID- 9288200
TI  - PET-methionine of skull base neuromas and meningiomas.
AB  - Eighteen patients with intracranial skull base tumours diagnosed at CT or MR as
      neuromas or meningiomas were studied with positron emission tomography (PET)
      using L-(methyl-11C) methionine. Compared with normal cerebellar tissue, the
      uptake of methionine in the tumours increased more rapidly and reached a higher
      level, and showed a slow decline after a peak occurring about 5 min after the
      injection. All the meningiomas exhibited considerably higher accumulation of the
      tracer compared with the surrounding cerebellar tissue, which made the tumour
      easy to identify and to demarcate from the surrounding cerebellar tissue, which
      made the tumour easy to identify and to demarcate from the surrounding structures
      (tumour to cerebellum ratios 2.62-5.37, mean 3.63). The uptake was homogeneous in
      all meningiomas, which were all of the syncytial type. The neuromas showed lower
      contrast against the cerebellum (tumour to cerebellum ratios 1.1-1.87, mean
      1.48). Some neuromas displayed an irregular pattern with regions of decreased
      tracer uptake corresponding to small cystic areas within the neuroma. There was
      no overlap in methionine uptake between the two tumour groups. The results
      indicate that PET-methionine may contribute to the evaluation, treatment planning
      and follow-up of patients with skull base meningiomas and neuromas.

PMID- 9288201
TI  - Sound-induced activation of auditory cortices in cochlear implant users with post
      and prelingual deafness demonstrated by positron emission tomography.
AB  - Changes of regional cerebral blood flow (rCBF) in the auditory cortices induced
      by sound stimulation were examined in nine postlingually and five prelingually
      deaf cochlear implant (CI) users by 15O-labeled water Positron Emission
      Tomography, and the results were compared with those of eight normal volunteers.
      Speech stimulation caused significantly greater rCBF increase compared with noise
      stimulation in the auditory association area in normal and postlingually deaf
      subjects. In prelingually deaf subjects, however, speech activation of the
      auditory association area was much less than that found in either of the other
      two groups. Neuronal networks for speech sound processing in the auditory
      association area in postlingually deaf individuals are thought be similar to
      those in normal subjects, while those in prelingually deaf patients who received
      CI after the speech acquisition period may not develop completely.

PMID- 9288202
TI  - Experimental sensorineural hearing loss following drill-induced ossicular chain
      injury.
AB  - In a guinea pig model, a standardized drill-induced injury to the body of the
      incus was applied, and the effects on hearing were characterized by
      electrocochleography. Drilling resulted in a threshold shift within seconds, and
      after 15 min it averaged 35.7 dB for clicks, 35 dB nHL for 4 kHz bursts, 36.7 dB
      nHL for 6 kHz bursts and 39 dB nHL for 8 kHz bursts. The deterioration of the
      threshold shift remained stable throughout the 5-week post-operative observation
      period. In five animals a disarticulation of the incudostapedial joint was
      performed prior to drilling, but this did not reduce the threshold shift. Caution
      is mandatory during drilling around an intact ossicular chain to avoid a
      permanent sensorineural hearing loss, and disarticulation of the incudostapedial
      joint prior to drilling has no protective value.

PMID- 9288203
TI  - Autoantibodies in inner ear disease.
AB  - The etiopathogenesis of many inner ear disorders still remains idiopathic.
      Immunological mechanisms are attracting attention in relation to a number of
      these diseases. Some cases are believed to be autoimmune in origin. The present
      study was conducted to determine whether patients with inner ear disorders
      produce antibodies that may be pathologic to the inner car or result from its
      damage. Sera from 100 patients with various inner ear disorders were tested for
      autoantibodies using the indirect immunofluorescence test. Inner ear tissue
      preparations from healthy guinea pigs were used as antigen substrates. Adequate
      tissue and serological controls were applied. Two groups of antibodies were
      detected; antibodies directed against the inner ear tissues (18%) and antibodies
      directed against different tissue/cellular elements (41%). A wide variety of
      inner ear antibodies were found, though no common type manifested itself.
      Meniere's disease was the most common clinical diagnosis in the antibody-positive
      group.

PMID- 9288204
TI  - Neural interaction in the human spiral ganglion: a TEM study.
AB  - A TEM study was performed on freshly fixed human spiral ganglions (HSG) collected
      during skull base surgery. This technique gives well preserved tissue for
      ultrastructural analysis. Unlike spiral ganglion cells in mature animals so far
      studied, most HSG cells lack a myelin coat, but are surrounded by a thin rim of
      Schwann cell (SC) cytoplasm. In the region of maximal innervation density (upper
      basal and middle turn), HSG cells were frequently ensheathed by the same Schwann
      cell, forming a "unit-like" structure. In this region the cells often showed
      signs of physical interaction where the SCs were frequently incompletely
      developed ("gaps") so that the cell membranes of adjacent ganglion cells
      (sometimes as many as four in one section plane) were in direct apposition. In
      one thin section as many as 20 of 100 ganglion cells were found to face the cell
      membrane, at any point, of an adjacent cell. At these "gaps" in the SC, complexes
      of cell membrane specializations occurred between individual HSG cells. The same
      nerve junctions were also found between unmyelinated nerve fibres and the body of
      large ganglion cells. Our findings may challenge the view that afferent
      information in the acoustic nerve is conveyed uninterrupted to the CNS at the
      level of the spiral ganglion.

PMID- 9288205
TI  - Morphological changes of stria vascularis in congenital hearing impairment due to
      membranous labyrinth underdevelopment.
AB  - Congenital malformations of the inner ear may involve either the bone and
      membranous labyrinth or the membranous labyrinth alone. The same labyrinth
      structures can be affected with an acquired disease, toxaemia or viral
      labyrinthitis, for instance, with the same or very similar histologic findings.
      So far, there have been no studies examining the possible morphological changes
      of stria vascularis in different diseases with sensorineural anomalies. We
      examined the temporal bones of 16 patients, from whom audiograms and history data
      on hearing impairments present at birth or later were obtained previously. When
      malformation of the membranous labyrinth was caused by a congenital anomaly,
      three groups of typical changes of stria vascularis were observed: i)
      pseudocystic formation which replaced the strial tissue, with dark-stained
      deposits: ii) accumulation of endothelial cells or irregularly shaped cells in
      the basal coil of the cochlea: and iii) atrophy of the stria vascularis tissue in
      all coils. These findings may prove important for accurate diagnostic procedures.

PMID- 9288206
TI  - Presence of glycosaminoglycans in the endolymphatic sac.
AB  - Earlier morphological investigations have revealed that the endolymph, which is
      present in the endolymphatic sac (ES) seems to differ from that found elsewhere
      in the labyrinth, in that it contains a stainable substance. Histochemical
      investigations indicate that this substance is rich in glycosaminoglycans (GAGs).
      It has been speculated that the stainable substance might play a role in
      regulation of fluid and ions and also, possibly, the pressure within the
      endolymphatic sac compartment. Endolymphatic sac specimens obtained from adult
      guinea pigs, rats, mice and in vitro cultured fetal inner ears were incubated
      with monoclonal antibodies against epitopes, and after enzymatic digestion
      revealed five different GAGs: hyaluronan, chondroitin-4-sulphate+dermatan
      sulphate, chondroitin-6-sulphate and keratan sulphate. In order to verify the
      specificity of these antibodies, otocysts from fetal mice were incubated in the
      same way. These cartilaginous specimens are known to contain GAGs in abundance
      and served as positive controls. The results indicate that the hyaluronan
      visualized by the monoclonal antibody is present to a large extent in the lumen
      of the ES and in the epithelial cells. Keratan sulphate and chondroitin-4
      sulphate+dermatan sulphate are present within the epithelial lining, in the
      subepithelial tissue, and to some minor extent in the lumen, while chondroitin-6
      sulphate does not show any specific staining.

PMID- 9288207
TI  - The mechanism and site of action of lidocaine hydrochloride in guinea pig inner
      ear.
AB  - Lidocaine was applied to the round window (RW) in order to localize its site of
      action in the cochlea. Cochlear microphonic (CM), summating potential (SP), and
      compound action potential (CAP) input/output functions were measured to a 16 kHz
      tone burst to assess the functional changes of the cochlea. In separate
      experiments, the effect of lidocaine on the whole cell current of isolated outer
      hair cells (OHC) was studied. A dose of 2 microliters of 40 mM lidocaine in
      saline solution, when applied to the RW, caused a small change in all measured
      variables, indicating a passage of the drug through the RW membrane to sites of
      action. However, 160 mM of lidocaine further decreased CM, SP, and CAP by a total
      of 40% from the control. A partial recovery occurred for CM during the 30 min
      follow-up period. CAP and SP continued to decline. In isolated OHCs, lidocaine
      decreased the whole cell current in a dose-dependent fashion. The KD for
      lidocaine effect on OHCs was 7 mM. Our in vivo results indicate that lidocaine
      affects OHCs and reduces CM, causing a subsequent reduction in SP and CAP. The
      increased effect of lidocaine on CAP and SP, while CM is recovering, suggests an
      additional specific effect of lidocaine on the cochlear nerve and/or on inner
      hair cells. Considering that lidocaine alters OHC current (in isolated hair
      cells) and that lidocaine does not affect endocochlear potential [Laurikainen et
      al. Acta Otolaryngol (Stockh) 1991: 112: 800-9], the observed CM changes are most
      likely due to an in vivo effect on OHCs. Thus, the early effect of lidocaine on
      the cochlea appears to be due to a significant change in organ of Corti function,
      rather than to direct anesthesia of the cochlear nerve. Later, an independent
      effect of the drug may occur on neural tissues in the inner ear.

PMID- 9288208
TI  - Electron probe X-ray microanalysis of otoconia in guinea pig inner ear: a
      comparison between young and old animals.
AB  - Using the electron probe X-ray microanalysis technique, the elemental composition
      of otoconia was analysed in both young and old normal pigmented guinea pigs.
      Calcium concentration in both the utricular and the saccular otoconia was lower
      in the old animals, which indicates that the loss of calcium from otoconia and/or
      decrease in calcium ion uptake may occur in the old animals. The present study
      has established that calcium and other elements (P, S, Cl and K) in the otoconia
      of the young animals are related via a linear function, indicating that P, S, Cl
      and K are present in the mineral phase of the otoconia. The associations of Ca-P,
      Ca-K and Ca-S are not maintained in the old animals. It has been suggested that
      the aging phenomenon may influence the ionic metabolism in the vestibular end
      organs resulting in the altered mineral composition of otoconia.

PMID- 9288210
TI  - Extracellular ATP-induced Ca2+ mobilization of type I spiral ganglion cells from
      the guinea pig cochlea.
AB  - Intracellular calcium concentrations ([Ca2+]i) in type I cochlear spiral ganglion
      cells (SGCs) of the guinea pig were measured by digital imaging microscopy and
      the Ca(2+)-sensitive dye Fura-2. Extracellular ATP induced elevation of [Ca2+]i
      in type I SGCs in a concentration-dependent manner. The ATP-induced elevation of
      [Ca2+]i in SGC was even evident in the Ca(2+)-free solution, thereby suggesting
      that ATP induces a Ca(2+)-release from intracellular stores in SGCs. Suramin and
      reactive blue 2, both antagonists for the P2-purinergic receptor, inhibited the
      [Ca2+]i increase in SGCs induced by extracellular ATP in a dose-dependent manner.
      Adenosine did not induce any changes of [Ca2+]i in SGC. These results suggest
      that type I SGCs may possess P2-purinergic receptor but not P1-purinergic
      receptor. Extracellular ATP induced a [Ca2+]i increase in type I SGCs, with and
      without neuritic processes, while L-glutamate increased [Ca2+]i in type I SGCs
      with neuritic processes, but not SGCs without neuritic processes. The ATP-induced
      [Ca2+]i increase was almost equal in both soma and processes. Therefore, the
      distribution of P2-purinergic receptor in type I SGCs may be homogeneous in soma
      and processes. Based on these observations, we suggest that extracellular ATP may
      act as a neurotransmitter or neuromodulator of the hair cell-afferent nerve
      synapse in the guinea pig cochlea.

PMID- 9288209
TI  - Formation and fate of giant otoconia of the guinea pig following streptomycin
      intoxication.
AB  - Formation and fate of abnormal (giant) otoconia of the guinea pig following
      streptomycin intoxication were investigated using scanning electron microscopy.
      The giant otoconia formed as multifaceted morphology in their early developmental
      period. They grew up the the transitional type and finally to the cylindrical
      type. It has been suggested that the giant otoconia found following streptomycin
      intoxication may be formed mainly by dissolution of normal otoconia due to the
      loss of environmental calcium, followed by recrystallization as giant crystals.
      These phenomena seemed to be closely related to the otoconial dynamics which may
      regulate calcium ion homeostasis of the endolymph.

PMID- 9288211
TI  - Ca(2+)-ATPases in the cochlear duct.
AB  - Differing levels of the Ca(2+)-ATPase enzymes that reside on the plasma membrane
      (PM) and on the endoplasmic reticulum (ER) were identified in individual rat
      cochlear tissues by the use of a semi-quantitative enzyme-linked immunosorbent
      assay (ELISA). Unlike other studies, a specific antibody to PM Ca(2+)-ATPase was
      used to detect significantly greater levels (about 2x) of PM Ca(2+)-ATPase in the
      stria vascularis (SV) than that in the spiral ligament (SL) and organ of Corti
      (OC) tissues. Similarly, levels of ER Ca(2+)-ATPase were also significantly
      higher in the SV than in the SL and OC tissues. The presence of ER Ca(2+)-ATPase
      in the tissues of the SV has not been demonstrated previously. Given the
      importance of Ca2+ homeostasis in the inner ear, the statistically significantly
      higher densities of both PM and ER Ca(2+)-ATPase measured in the SV relative to
      the SL and OC regions would indicate tissue-specific responses to fluctuations in
      systemic and local Ca2+ concentrations.

PMID- 9288212
TI  - In vivo vestibular blood flow in the Mongolian gerbil: angiotensin III-provoked
      changes in systemic and local factors.
AB  - The current literature contains little information on vestibular end organ blood
      flow. The absence of an accepted model, difficulties applying dynamic in vivo
      measurement techniques and the inaccessibility of the inner ear organs contribute
      to the shortage of experimental findings. The purpose of the current study is to
      introduce the gerbil as a viable model for the in vivo study of vestibular blood
      flow dynamics. The potent vasoactive peptide, angiotensin III (AIII), was used to
      provoke blood pressure and blood flow changes. The results of this study
      demonstrate that viable blood flow measures may be obtained from the vestibule of
      the gerbil. Dose-dependent changes in blood pressure and vestibular blood flow
      were observed in response to high concentrations of AIII. Pretreatment with the
      receptor antagonist, sarthran, attenuated both blood pressure and blood flow
      increases in response to subsequent AIII infusions. The gerbil model offers the
      advantages of easily accessible and identifiable peripheral vestibular organs, as
      well as responsive local blood flow. Investigations using this model may provide
      information on the regulation of blood flow during presentation with a variety of
      stimulus modalities. Information from such studies may lead to development of
      strategies for treatment of vestibulopathies suspected to be of vascular origins.

PMID- 9288213
TI  - Middle ear inflation as a treatment for secretory otitis media in children.
AB  - Clinical evaluations of middle ear inflation for secretory otitis media (SOM)
      were performed with special emphasis on the influence of seasonal and aging
      factors. One hundred and forty-nine children between the ages of 3 and 9 years
      (227 ears) were all diagnosed as SOM by pneumatic-otoscopic findings, and type B
      tympanogram (TG) at 3 weeks or more after the onset of acute SOM or the initial
      observation of SOM. Middle ears were inflated by Politzer's method or by our
      modified method once or twice each week for 2 months. After inflation, TG
      displayed two different time sequences: one group changed to the A or C type
      immediately after inflating the ear one or more times, but usually returned
      gradually to the B type (TG-improved group): and the other group remained without
      any changes (TG-unchanged group) for the duration of this study. The healing rate
      in the TG-improved group was significantly higher than in the TG-unchanged group
      at the 2-month endpoint. The cure rate of SOM was significantly higher in spring
      than in autumn in the TG-unchanged group but not in the TG-improved group. There
      were almost no differences between the healing rates in the 3-5 and 6-9 year-old
      children. When a TG-unchanged ear is found in autumn during the 2-month inflation
      treatment, more careful and forcible treatments should be introduced later,
      especially to children between the ages of 3 and 9 years.

PMID- 9288214
TI  - Early post-tympanostomy otorrhea in children under 17 months of age.
AB  - A total number of 281 consecutive children with recurrent acute otitis media
      (RAOM) or otitis media with effusion (OME) was treated with ventilation tubes
      (VT), inserted under local anesthesia. Patients were prospectively followed-up
      for post-tympanostomy otorrhea, classified as "early" if observed within 7 days
      of the tympanostomy procedure. The age of children ranged from 5 to 16 months
      (average 10.1 months). VT were placed bilaterally in 279 of 281 children. The
      average length of otitis media (OM) history prior to tympanostomy was 3.4 months.
      An episode of OM had been diagnosed 1-2 times in 18.9%, 3-4 times in 68.0%, and
      at least 5 times in 13.1% of the children. Middle ear effusion (MEE), most often
      classified as mucoid was present in 65.8% of the ears. Cultures were positive for
      bacteria in 41 of the 185 ears with MEE (22.2%). The mastoid air cell system was
      radiographically normal in 9.6% and markedly clouded in 56.6%. Early post
      tympanostomy otorrhea was observed in 16.0% of ears, occurring more often when
      MEE, especially mucopurulent, was present at tympanostomy (p < 0.01). The risk of
      otorrhea was significantly increased by a positive culture for pathogenic
      bacteria in MEE (p < 0.01) and highly significantly by the advanced opacification
      of the mastoid air cell system (p < 0.001). It is concluded that early post
      tympanostomy otorrhea in young children is caused by the advanced infectious
      process in the middle ear cleft, including mastoid cell system rather than by the
      tympanostomy procedure itself. It may indicate the need for more active treatment
      in this age group.

PMID- 9288215
TI  - Influence of the upper respiratory tract infection on tubal compliance in
      children with otitis media with effusion.
AB  - To clarify the influence of inflammation on tubal compliance in children with
      otitis media with effusion (OME), we investigated the change of compliance of the
      ET by upper respiratory tract infection (URTI) in 18 children (23 ears) with OME
      using the forced response test. The tubal compliance index (TCI), the ratio of
      passive tubal resistances at two different airflow rates, significantly increased
      during URTI represented by acute rhinitis or paranasal sinusitis in comparison
      with non-URTI periods (paired t-test: t = 4.14, p < 0.001). In nine ears, the TCI
      could be followed for some months after that, during which the children had had
      URTI several times. A clear reproducible correlation was found between the
      presence or absence of URTI and the TCI values; the TCI values increased again
      during URTI and decreased after the URTI periods. These results seemed to support
      our hypothesis that compliance of the ET may depend not only on the property of
      the cartilaginous framework of the ET but also upon the mucosal condition.

PMID- 9288216
TI  - Recurrent acute otitis media: the significance of age at onset.
AB  - In order to assess the relationship between recurrent acute otitis media (rAOM)
      and age at first acute otitis media (AOM) episode, a prospective cohort of 3754
      Norwegian children born in 1992-1993 was followed from birth to 2 years.
      Recurrent acute otitis media was defined by the criterion of four or more
      episodes of AOM during a 12-month period. Approximately 5.4% of the children
      experienced rAOM before the age of 2. Furthermore, children whose first AOM
      episode occurred before the age of 9 months were at a significantly higher risk
      for developing rAOM compared to children whose first AOM episode was 10-12
      months. In children who had the first ear infection during the first 9 months of
      life, one-quarter developed rAOM before the age of 2. Multiple logistic
      regression analysis adjusted for confounding showed that gender and a familial
      history of atopy were significantly associated with rAOM. In conclusion, the
      present study found an association between age at first AOM episode and the later
      subsequent AOM proneness. Additionally, both gender and a family history of atopy
      seemed to predispose towards otitis-proneness.

PMID- 9288217
TI  - Endoscopy and otomicroscopy in the estimation of middle ear structures.
AB  - In order to study the variation within and between endoscopy and otomicroscopy a
      Gage repeatability and reproducibility design was created, with which the middle
      ears were studied of eight cadaver temporal bone blocks through the ear canal
      three times in random order using both methods. A Zeiss OPMT-1 operating
      microscope and Olympus endoscopes were used. The data were analysed in accordance
      with the analysis of variance principle, where the total variation was divided
      into different components. The anatomical areas were counted and registered via
      quadrants. There was a distinct difference between the results of the two methods
      in favour of the endoscopes. Furthermore, the variation between the methods and
      between the trials was analogous.

PMID- 9288218
TI  - Spontaneous changes of unilateral nasal airflow in man. A re-examination of the
      'nasal cycle'.
AB  - It is now over 100 years since Kayser (Archiv fur Laryngol Rhinol 1895; 3: 101
      120) first reported in the scientific literature that the human nasal passages
      exhibit spontaneous changes in unilateral nasal airway resistance, yet our
      understanding of this unusual phenomenon is still very confused. Spontaneous,
      reciprocal changes in unilateral nasal resistance are often referred to as a
      "nasal cycle" and although this term is now commonly used to describe spontaneous
      changes in nasal resistance in man and animals, there is little evidence for any
      true periodicity. A major problem in increasing our knowledge and understanding
      of the so-called "nasal cycle" is that most studies have relied on simple
      descriptions of the changes in nasal resistance and have not developed any
      numerical parameters to quantify the changes in resistance over time. This lack
      of definition of what actually constitutes a nasal cycle has meant that the
      literature of the present day generally accepts the views put forward by
      Heetderks (Am J Med Sci 1927; 174; 231-244) and Stoksted (Acta Otolaryngol
      (Stockh) 1953; Suppl 109: 159-175) that around 80% of the healthy population
      exhibit a regular cycle. In order to define the characteristics of the
      spontaneous changes in nasal airway resistance we have used numerical measures of
      reciprocity and also developed a measurement of the division of airflow between
      the nasal passages over time. With these two parameters it is possible to
      describe the nature of the spontaneous changes in airflow in numerical terms and
      to define what exactly constitutes a nasal cycle. Fifty-two volunteers underwent
      hourly measurement of unilateral nasal airflow for 8 h. For each volunteer, two
      values were derived from the graph of unilateral nasal airflows against time; the
      correlation coefficient between unilateral airflows (r) and the airflow
      distribution ratio between the two nasal airways (ADR). The spread of different
      types of airflow pattern (nasal cycle) throughout the population was illustrated
      by plotting r against ADR for each subject. A nasal cycle was defined as having
      an r value between -0.6 and -1.0, and an ADR value between 0.7 and 1.0. Only 21%
      (11 of the 52 volunteers) exhibited airflow patterns that could be defined as a
      nasal cycle in these terms. This finding contradicts the generally accepted, but
      undefined, view that around 80% of the population exhibit a regular nasal cycle.
      The numerical definition of a nasal cycle in terms of both reciprocity and
      airflow distribution, as described in this paper may help to clarify our
      understanding of this interesting phenomenon and allow rhinologists to describe
      the spontaneous changes in nasal airflow in more exact terms than have been used
      previously in the literature.

PMID- 9288219
TI  - Physiological fluctuations in nasal resistance may interfere with nasal
      monitoring in the nasal provocation test.
AB  - The physiological fluctuations in nasal flow and resistance in allergic subjects
      were studied by monitoring 12 subjects with perennial occupational allergic
      rhinitis with active anterior rhinomanometry (AAR) for 3 h at 15 min intervals.
      The subjects were then challenged bilaterally with the diluent solution for
      allergen extracts and the effect was monitored with AAR. In AAR. cellular rubber
      nose adapters were used. Many physiological fluctuations in nasal patency were
      observed. Reference intervals were calculated for the changes in flow and
      resistance at the gradient pressure of 150 pa. For example, a 100% increase in
      unilateral resistance was found to be significant at the risk level of 5-10% for
      the observation time of 30-60 min. The corresponding increase for bilateral
      resistance was close to 70%. Challenge with diluent solution had a negliglible
      effect on the resistance fluctuation, the reference intervals being close to
      those for baseline monitoring. In conclusion, rapid changes in nasal flow and
      resistance in allergic subjects were common, and caution is necessary when
      interpreting these changes as a positive nasal reaction in the nasal provocation
      test. In addition, the use of other objective parameters, such as the amount of
      nasal secretion is recommended.

PMID- 9288220
TI  - Comparison of functional results after ethmoidectomy and nasalization for diffuse
      and severe nasal polyposis.
AB  - Taking advantage of a natural experimental situation, we compared,
      retrospectively, functional results after nasalization and ethmoidectomy for
      diffuse nasal polyposis. Nasalization was a radical ethmoidectomy systematically
      removing all the bony lamellae and mucosa within the labyrinth, with large
      antrostomy, sphenoidotomy, frontotomy, and middle turbinectomy (Surgeon 1, 39
      consecutive patients operated on between March and September 1991). Ethmoidectomy
      was a less systematic procedure, that was adapted to the extent of the pathology
      (Surgeon 2, 37 consecutive patients, operated on between October 1991 and
      November 1994). In May 1994, a third physician mailed a questionnaire
      simultaneously to all patients including 10-point visual analog scales 34/39
      patients in the nasalization group (age: 28-71 years: 20 asthmatics; follow-up:
      32-36 months), and 29/37 patients in the ethmoidectomy group (age: 26-65 years: 9
      asthmatics: follow-up: 18-31 months) participated in the study. The overall nasal
      improvement was 8.8 +/- 0.2 (mean +/- SEM) after nasalization and 5.9 +/- 0.6
      after ethmoidectomy (p = 0.0001). Olfaction improvement was similar in both
      groups 6 months after surgery, remained at the same level 36 months after
      nasalization (6.9 +/- 0.7), but decreased to 4.2 +/- 1 points 24 months after
      ethmoidectomy (p = 0.02). Asthma improvement remained significantly better after
      nasalization (p = 0.05), and the need for systemic steroids was also lower (p =
      0.03). Results of this study suggest that when dealing with nasal polyposis, the
      more radical the surgery, the better the functional results.

PMID- 9288221
TI  - Post-exercise nasal vasoconstriction and hyporeactivity: possible involvement of
      neuropeptide Y.
AB  - Neuropeptide Y (NPY) is co-localized with noradrenaline (NA) in perivascular
      sympathetic nerve and is a vasoconstrictor. Pre-treatment with exogenous NPY
      markedly reduced nasal airway obstruction and rhinorrhea induced by the irritant
      capsaicin in control subjects. The aim of the present experiments was to study
      the time course variations of plasma concentrations of NA and NPY during and
      after intense exercise in 17 healthy volunteers. In parallel, changes in nasal
      airway resistance (NAR) were recorded. Nasal obstruction and rhinorrhea induced
      by capsaicin were compared after 30 min of rest and after 30 min of exercise.
      Both subjective and objective NAR were significantly reduced (p < 0.05) for over
      15 min after the end of exercise. Plasma levels of NPY remained increased for
      more than 15 min after exercise whereas NA returned to basal values within less
      than 10 min. The increases of NAR and mucus production evoked by capsaicin were
      markedly attenuated for 30 min after exercise (p < 0.05). Variations of plasma
      NPY concentrations over time correlated better with post-exercise nasal
      vasoconstriction and hyporeactivity to capsaicin than NA. These observations
      suggest that endogenous NPY could be involved in the prolonged post-exercise
      nasal vasoconstriction and acts as a modulator of nasal airways reactivity.

PMID- 9288222
TI  - Changes in nasal nitric oxide concentration associated with symptoms of common
      cold and treatment with a topical nasal decongestant.
AB  - Nitric oxide (NO) is known to play a role in the non-specific host defence
      mechanism. Furthermore, it has been proposed that NO may be important in
      respiratory defence against the viruses which cause the common cold. Indeed,
      elevated NO levels have previously been observed in orally expired air during
      upper respiratory tract infection (URTI). We wanted to investigate further the
      role of NO in the host response to URTI. Total nasal airway resistance (tNAR) and
      nasal NO levels were obtained during symptomatic URTI in 97 subjects. Of these,
      80 received treatment with either oxymetazoline or a placebo spray. Post
      treatment tNAR and NO levels were obtained 60 min after treatment. Measurements
      of NO were also repeated 4-6 weeks later, when subjects were healthy, (n = 82).
      NO levels were measured using a chemiluminescence gas analyse whilst tNAR was
      measured using posterior rhinomanometry. The mean pre-treatment NO level (1063 +/
      541 ppb) was shown to be reduced significantly after treatment with
      oxymetazoline (827 +/- 373ppb), p < 0.0001. The mean pre-treatment tNAR, 0.42 Pa
      cm-3 sec-1, was also reduced significantly to 0.21 Pa cm-1 sec-1 (p < 0.001)
      after treatment with oxymetazoline. There was no significant correlation between
      the change in NO levels and change in tNAR following treatment with oxymetazoline
      (p. corrected for ties = 0.011, p = 0.98. No significant difference was found
      between NO levels obtained during URTI (1130 +/- 444 ppb) when compared to values
      obtained when healthy (1197 +/- 361 ppb), p = 0.25. These results demonstrate
      that treatment with a topical nasal decongestant spray causes a reduction in
      nasal NO levels. We propose that this occurs as an indirect consequence of the
      vasoconstrictor actions of oxymetazoline. Since no change in NO levels was
      observed during URTI, we propose that the NO synthase responsible for NO
      production in the nose responds in a different manner to that in the lungs.

PMID- 9288223
TI  - Clindamycin in recurrent group A streptococcal pharyngotonsillitis--an
      alternative to tonsillectomy?
AB  - Fifty-three patients with bacterial treatment failure after a 10-day course of
      treatment with phenoxymethyl penicillin (pcV) for group A streptococcal (GAS)
      pharyngotonsillitis were randomly assigned to continued treatment with pcV, or to
      treatment with clindamycin instead. The patients were then followed for 1 year
      with throat cultures and clinical examination every third month and in the event
      of symptoms of sore throat. In the first 3-month period, 15/22 patients in the
      pcV group yielded one or more positive cultures for GAS, all of the same T-type
      as in the original throat culture, as compared to 3/26 in the clindamycin group
      (p < 0.001). All three cases in the clindamycin group were due to a new T-type
      and thus were re-infections. In the pcV group, owing to repeated treatment
      failure, 12/22 patients were switched to treatment with clindamycin within the 3
      month period following the second treatment. During the remainder of the 1-year
      follow-up period, sporadic cases of GAS-positive throat cultures occurred in both
      groups, but there was no significant difference in frequency between the two
      groups. It is concluded that, in patients with GAS pharyngotonsillitis and
      failure after pcV treatment, a 10-day course of clindamycin can protect the
      patient from recurrence for at least 3 months and might be an alternative to
      tonsillectomy.

PMID- 9288224
TI  - Warthin's tumour associated with autoimmune diseases and tobacco use.
AB  - To better clarify the possible role of immune mechanisms in the pathogenesis of
      Warthin's tumour (WT), we performed a retrospective study of patients with WT
      surgically treated at the Institute of Otolaryngology Head and Neck Surgery,
      University of Florence, during a 25-year period; looking for a possible
      association with autoimmune pathologies. The retrospective analysis of clinical
      records of 140 WT patients compared with those of 380 patients with pleomorphic
      adenoma revealed a higher incidence of autoimmune disorders, particularly organ
      specific disease (i.e. insulin-dependent diabetes mellitus, Hashimoto's
      thyroiditis, autoimmune hyperthyroidism and hypothyroidism) in WT patients than
      in pleomorphic adenoma (PA) patients (23% vs 3%; R.R.: 8.69; p < 0.0001).
      Moreover, we demonstrate a positive smoking history in 87% of WT patients
      compared to only 38% of PA subjects (p < 0.001). Because of the well-known
      possible association among multiple immune disorders, our data support the
      hypothesis of an immune pathogenesis of WT and also suggest the possible role of
      tobacco smoke in facilitating such immune reactions responsible for the lympho
      epithelial coexistence of WT.

PMID- 9288225
TI  - A simple and reliable technique for culturing of human oral keratinocytes and
      fibroblasts.
AB  - Cultures of non-malignant oral cells are needed for many applications in the
      field of oral biology. We describe an efficient and rapid method for the culture
      of both keratinocytes and fibroblasts isolated from oral tissue, uvulas from
      patients undergoing reconstructive surgery and non-cancerous tissue from oral
      cancer patients. High cell yields with a high purity could be obtained. The
      technique is described in detail with respect to isolation of the cell types, the
      best way to propagate for over 5 passages and to measure cell proliferation in a
      colorimetric assay. Culture was successful in over 80% of cases for keratinocytes
      and over 63% for fibroblasts. Problems encountered were the risk of
      microbiological infection, the size of the specimen and the type of culture
      medium used. The potential applications of these primary cell cultures are
      mentioned.

PMID- 9288226
TI  - Effects of acidic and basic fibroblast growth factors on cell proliferation in
      pleomorphic adenoma of the parotid gland.
AB  - Localization and biochemical characteristics of acidic and basic fibroblast
      growth factor (aFGF and bFGF) were studied in the normal parotid gland (NPG) and
      in pleomorphic adenoma (PA). In addition, the effects of these factors on
      proliferation activity were investigated in cultured PA cells. aFGF and bFGF were
      detected immunohistochemically in 62% and 58% of NPG and 44% and 58% of PA,
      respectively, and they localized in the cytoplasm of the ductal segments of the
      NPG, and of the tubular, trabecular and squamous components of PA. Both aFGF and
      bFGF, each with a molecular weight of 18 kDa, were identified in PA using heparin
      sepharose chromatography and Western blot analysis. Both recombinant human aFGF
      and bFGF stimulated [3H]-thymidine incorporation by cultured PA cells. These
      results indicated that aFGF and bFGF, probably produced by neoplastic cells, play
      important roles in the proliferation of PA of the parotid gland.

PMID- 9288227
TI  - Acoustic neuroma/vestibular schwannoma in vivo and in vitro growth models. A
      clinical and experimental study.

PMID- 9288228
TI  - Asialo GM1-positive cells in mouse cochlea.
AB  - The presence of ganglio-N-tetraosylceramide (asialo GM1)-positive cells in mouse
      cochlea was tested for using an immunohistochemical method with an anti-asialo
      GM1 antibody which reacts with natural killer cells and macrophages in mouse.
      Only a few asialo GM1-positive cells were present on the surface of the scala
      tympani of the basal turn near the collecting venules. Transmission electron
      microscopic study showed the internal structure of these cells to be that of
      macrophages. These findings suggest that asialo GM1-positive cells function as
      resident type macrophages against invasion by pathogens of the mouse cochlea.

PMID- 9288229
TI  - Preliminary study of the role of endothelin-1 in the homeostasis of the inner
      ear.
AB  - Endothelin (ET), originally characterized as a 21-residue vasoconstrictor peptide
      from endothelial cells, has been reported to act as a local hormonal regulator of
      pressure, fluid, ions, and neurotransduction. Our previous studies suggested an
      important role of ET-1 in the inner ear. The present study investigated the time
      kinetics of ET-1 in the epithelium of the endolymphatic sac (ES) of guinea pigs
      and its relation to the development of endolymphatic hydrops (EH) following
      locally mounted secondary immune reaction. In the duration between 12 h and day
      1, ET-1-like activity completely disappeared from the epithelium of the ES and
      was associated with the accumulation of inflammatory cells in the ES and a rapid
      development of EH. On day 7, ET-1-like activity recovered as a consequence of the
      decrease of inflammatory cells and reduction of EH. These findings suggest that
      ET-1 may play an important role as one of the regulators maintaining the fluid
      balance.

PMID- 9288230
TI  - Anionic sites of charge barrier in the guinea pig crista ampullaris.
AB  - In present studies we obtained anionic sites in the epithelial and capillary
      basement membranes in the dark cell area of the crista ampullaris in the guinea
      pig. The immersion method with cationic tracer polyethyleneimine (PEI) was
      applied. Electronmicroscopically, the arrangement of PEI particles was observed
      as two strata along the basement membrane. The number of particles could be
      counted and compared in each portion. The control test with protamine sulfate
      showed that the number of PEI particles decreased in both the epithelium and
      capillaries of the dark cell area. In the experiment using furosemide, the stria
      vascularis and the dark cells had changed, with pathological findings of
      interstitial edema and PEI particles reduced in number. It is suggested that the
      PEI particles reflect different conditions of charge in the basement membrane,
      which influences the production or absorption of the inner ear fluid.

PMID- 9288231
TI  - Induction of free radicals in the cochlea by an aminoglycoside antibiotic.
AB  - Free radicals are known to cause damage to biological tissues. We used
      histochemical methods to examine the emergence of free radicals in kanamycin (KM)
      treated guinea pig cochlea. As a preliminary in vitro study, the emergence of
      free radicals was observed in guinea pig cochlea incubated with KM. In an in vivo
      study, KM was placed on the guinea pig round window membrane and the emergence of
      free radicals was observed over time. The emergence of free radicals was observed
      along the luminal membrane and hair bundles of outer hair cells. The appearance
      and disappearance of free radicals in the cochlea coincided with the transport of
      KM into the inner ear. These findings suggest that the emergence of free radicals
      could be attributed to the administration of KM.

PMID- 9288233
TI  - Measurement of pressure and displacement of the membranous labyrinth in
      endolymphatic hydrops by the tensile test.
AB  - We measured the mechanical characteristics, particularly the strength of various
      regions of the membranous labyrinth by the penetration test with a specially
      designed machine. A load-displacement curve was drawn by the tensile test for the
      Reissner's and basement membranes. Additionally, a stress-strain curve was drawn.
      The modulus of elasticity was measured showing a straight line in the stress
      strain curve: 1.5 x 10(2) mN/mm2 for Reissner's membrane and 9.3 x 10(2)-1.3 x
      10(3) mN/mm2 for the basement membrane. Furthermore, the endolymphatic pressure
      was calculated at the point in time when the maximum strain as the limit of
      elasticity was 0.2. It was 81 Pa. The displacement of Reissner's membrane was 0.2
      mm when the initial tension was taken as 0 in the formula, and that of the
      basement membrane was 3 to 37 microns when the initial tension was 0, 0.1, 0.2
      and 0.3.

PMID- 9288232
TI  - Effect of gentamycin on the melanosomes in the stria vascularis of the pigmented
      guinea pig: an ultrastructural study.
AB  - Melanosomes of the stria vascularis in gentamycin (GM)-intoxicated guinea pigs
      were examined ultrastructurally. Experimental animals were given GM sulfate
      intramuscularly in a daily adjusted dose of 100 mg/kg for 15 consecutive days
      (group A), and 150 mg/kg for 5 consecutive days (group B). Melanosomes of the
      intermediate cells in group B significantly increased in number in comparison
      with those in group A and the control group. Melanosomes in the apical turn
      outnumbered those in the basal turn in all three groups. Cytochemically, Na+,
      K(+)-ATPase activity was also demonstrated in the marginal cells. There was
      little difference in the degree of enzyme activity between groups A, B and the
      control group. The role and significance of melanosomes of the stria vascularis
      are discussed.

PMID- 9288235
TI  - The origin of thermally evoked vestibular potential.
AB  - The origin of the thermally evoked ampullary nerve action potential was searched
      using isolated frog posterior semicircular canal (PSC). The PSC was placed in the
      dish with 2 chambers separating endo- and perilymphatic fluid. Cooling stimulus
      was given by approximating the iced bar to the ampulla, and induced action
      potential (CAP) was recorded. When only the endolymph contained Ca2+, no CAP was
      evoked, while, the perilymph contained Ca2+, CAP was observed. These findings
      were comparable between with and without cupula. When only the endolymph
      contained tobramycin (TOB), the spike count did not change. However, when TOB was
      added into the perilymph, the spike count decreased according to concentration of
      TOB. When TOB was washed out, the spike count recovered. These findings were also
      comparable between with and without cupula. The above results indicate that
      thermally evoked vestibular potentials possibly originate in the hair cell.

PMID- 9288234
TI  - Effect of histamine on intracellular Ca2+ concentration in guinea pig isolated
      vestibular hair cells.
AB  - The present study examined the effects of histamine in the guinea pig isolated
      vestibular hair cells (VHCs) by measuring the dynamic changes of intracellular
      free calcium ion ([Ca2+]i) concentration using calcium sensitive dye Fura-2. The
      histamine-induced calcium response in VHCs was markedly increased at the
      concentration of 10 microM histamine in the presence of extracellular Ca2+, while
      in the absence of extracellular Ca2+, a slow increase of [Ca2+]i was evident.
      Receptor specificity of the response to histamine was examined: promethazine (H1
      receptor antagonist), cimetidine (H2 receptor antagonist) and thioperamide (H3
      receptor antagonist) completely blocked the histamine-induced calcium response at
      the concentrations of 2.5 microM, 1.0 microM and 1.0 nM, respectively. The
      responses were mediated by H1, H2 and H3 receptors and resulted in a rise of
      [Ca2+]i due to an influx of Ca2+ from the extracellular space and a release from
      intracellular stores. Our preliminary data suggest that under immuno-pathological
      conditions of the inner ear, histamine released from the mast cells distributed
      in the endolymphatic sac may act through receptors located on the vestibular hair
      cell membrane and may regulate the cell function and the signal transduction in
      the vestibular nerve-hair cell afferent system.

PMID- 9288236
TI  - Utricular input to cat extraocular motoneurons.
AB  - Intracellular recordings from 200 identified extraocular motoneurons in the
      bilateral III, IV and VI cranial nuclei were studied to determine the
      connectivities between the utricular nerve and the extraocular motoneurons in
      cats. Stimulating electrodes were placed within the left utricular nerve, while
      other branches of the vestibular nerve were removed. Monosynaptic and disynaptic
      connections between the utricular nerve and the ipsilateral abducens motoneurons
      and interneurons were recorded as described previously. Stimulation of the
      utricular nerve evoked longer latency depolarizing and hyperpolarizing potentials
      in contra- and ipsilateral medial rectus motoneurons, respectively. Depolarizing
      and hyperpolarizing potentials with longer latencies were also recorded in the
      ipsilateral inferior oblique and contralateral trochlear motoneurons. The short
      and longer latency circuits between the utricular nerve and extraocular
      motoneurons may play a role in stabilizing the retinal image during head tilt and
      horizontal linear acceleration.

PMID- 9288237
TI  - Connections between otolith receptors and neck motoneurons.
AB  - Intracellular recordings from ipsilateral and contralateral neck extensor and
      flexor motoneurons were studied to determine the connections between the
      utricular nerve and neck motoneurons and between saccular nerves and neck
      motoneurons in cats. Stimulating electrodes were placed within the left utricular
      nerve or saccular nerve. Electrical stimulation of the utricular nerve evoked
      excitatory postsynaptic potentials (EPSPs) with disynaptic latency in almost all
      ipsilateral extensor motoneurons and disynaptic EPSPs in all ipsilateral flexor
      motoneurons. In contralateral extensor and flexor motoneurons, the initial
      response to utricular stimulation was usually inhibitory postsynaptic potentials
      (IPSPs) with trisynaptic linkage. Thus, the utriculo-neck connectivities
      essentially differentiated between the left and right side. In response to
      stimulation of the saccular nerve, the initial response in bilateral extensor
      motoneurons ws EPSPs. Ipsilateral projections were always disynaptic;
      contralateral projections could be di- or trisynaptic. IPSPs were evoked in
      almost all bilateral flexor motoneurons with di- or trisynaptic latencies. The
      sacculo-neck motoneuron relationship thus has a qualitatively, bilaterally
      symmetric organization with regard to flexors and extensors.

PMID- 9288239
TI  - Excitatory synaptic transmission in the rat medical vestibular nucleus.
AB  - In vitro brainstem slice preparations have provided the opportunity to obtain
      accurate information about the neuropharmacology of the vestibular system. By
      stimulating the root of the eighth cranial nerve, excitatory synaptic
      transmission in the rat medial vestibular nucleus has been observed and analyzed
      with extra- and intra-cellular recordings. Recently, tight-seal, whole-cell
      recordings, perforated whole-cell recordings and microfluorometry of Ca2+ were
      applied to in vitro brainstem slice preparations to obtain detailed information.
      Excitatory synaptic transmission to MVN neurons is reviewed.

PMID- 9288240
TI  - Effect of isosorbide on distortion-product otoacoustic emissions and endocochlear
      DC potential in experimentally induced hydropic ears.
AB  - The effects of isosorbide on distortion-product otoacoustic emissions (DPOAEs)
      and endocochlear DC potential (EP) were examined in experimentally induced
      endolymphatic hydropic ears and untreated control ears using 20 albino guinea
      pigs. DPOAEs and EP in the hydropic ears decreased after obliteration of the
      endolymphatic duct and sac. The administration of isosorbide restored DPOAEs to
      the normal level, whereas EP was further reduced. In control ears there was no
      significant change in DPOAEs and EP after the administration of isosorbide. The
      results obtained in the present study indicate that the effect of isosorbide on
      DPOAEs is different from that on EP, and the recovery of DPOAEs in hydropic ears
      is not a secondary phenomenon due to the recovery of EP.

PMID- 9288238
TI  - Effects of newly developed excitatory amino acid antagonists on vestibular type I
      neurons in the cat.
AB  - A newly synthesized compound NC-1200 (oxazolidinone) has been shown to have a
      powerful inhibitory action on the glutamate response at the neuromuscular
      junction in crayfish where glutamate is thought to be an excitatory
      neurotransmitter. However, the pharmacological function of NC-1200 in the CNS of
      mammals remains unknown. We examined the glutamate blocking action of NC-1200 on
      various glutamate receptors of cat's vestibular neurons. The effects of NC-1200
      on secondary vestibular neurons were studied by intra-venous (3-5 mg/kg) and
      iontophoretic application using multi-barreled electrodes filled with NMDA,
      kainic acid and NC-1200 in decerebrated cats. After identification of type 1
      neurons, the chemicals were applied to examine their effects on neuronal
      activity. The results were as follows; i) Systemic application of NC-1200
      suppressed type 1 responses to yaw rotation; ii) both NMDA-mediated and kainate
      mediated excitations on the vestibular neurons were abolished by application of
      NC-1200; iii) the suppression of various glutamic receptors was dose-dependent;
      and iv) the kainate receptor was more strongly suppressed than the NMDA receptor
      by NC-1200.

PMID- 9288241
TI  - ABR findings, electrocochleograms and caloric tests in vertebrobasilar ischemic
      rats.
AB  - In rats with ischemia induced by occlusion of the anterior inferior cerebellar
      artery (AICA) or vertebral artery (VA), we investigated the auditory brainstem
      response (ABR), electrocochleogram and caloric test result. Upon occlusion of the
      VA, there was no change of the ABR, whereas in the caloric test the duration of
      nystagmus upon stimulation of both ears shortened. Upon occlusion of the AICA,
      the cochlear blood flow (CoBF) showed one of three patterns of change no change:
      n = 5; decrease: n = 10; and transient decrease with recovery: n = 5. The
      cochlear potentials were dependent on the residual CoBF. In the caloric test,
      when the left AICA was occluded, the duration of nystagmus induced by stimulation
      of the left (ipsilateral) ear was shorter than that induced by the right
      (contralateral) ear. Based on the functional test results, we conclude that in
      this model of ischemia the function of the vestibular structures including the
      semicircular canals is more severely affected than is the hearing function.

PMID- 9288242
TI  - Light-weight and low-cost infrared CCD eye monitoring system designed for routine
      vestibular clinic use.
AB  - A simple and low-cost eye monitoring system with infrared illumination was
      developed. This system consists of a small board mounted with an infrared
      sensitive CCD camera and its control unit and a swimming goggle; it is light
      weight and visualizes eye movements by connecting the output lines of the board
      to the video input on a monitor. We have found the present system useful in the
      routine vestibular clinic practice.

PMID- 9288243
TI  - Vestibulo-ocular reflex and visual vestibulo-ocular reflex during sinusoidal
      rotation in children.
AB  - To clarify the relationship between vestibular and visual (optokinetic) stimuli
      in normal children, we investigated the vestibulo-ocular reflex (VOR) and visual
      VOR (VVOR). The subjects were 20 healthy children aged 3-6 years and 24 healthy
      adults aged 21-29 years. The VOR gains and phase were measured under two visual
      conditions: with eyes open in complete darkness and with eyes open in a lighted
      optokinetic drum. In both visual conditions, phase did not significantly differ
      between children and adults. In the dark, children presented a significantly
      larger gain than that of adults. In the optokinetic drum, however, the gain
      values of the children were almost the same as in adults. We suggest that the
      large VOR gain values of children may be due to immaturity of the inhibitory
      regulation system of the VOR.

PMID- 9288244
TI  - Clinical significance of the subjective vertical in patients with unilateral
      vestibular disorders.
AB  - The subjective vertical was estimated by using a concentrically movable spotlight
      line on a specially devised dome-shaped screen and a controller in patients with
      unilateral vestibular disorders. The test was performed in a dark room to measure
      the deviation of the subjective vertical from the true vertical to the earth
      gravity. The result showed characteristic deviation of the subjective vertical to
      the affected ear side in most subjects. The relationship between the subjective
      deviation and body sway was investigated to estimate the clinical significance of
      the subjective vertical. The locus pattern, area, locus length and the trajectory
      of head movements while measuring the subjective vertical were recorded. The
      patterns were centripetal or right-left types, the values of the head movement
      seemed to be proportional to the magnitude of the subjective vertical. The time
      course of the subjective vertical depended on the stage of the disorder. Some
      cases with active vestibular disorders showed directional changes of the
      subjective vertical deviation depending on the extent of the lesion. The most
      interesting results were obtained in the relationship between the caloric
      response and the subjective vertical, suggesting the clinical significance of the
      subjective vertical in vestibular function.

PMID- 9288245
TI  - 3D analysis of nystagmus during peripheral vertiginous attacks.
AB  - In order to localize the site of lesion of peripheral vertigo, 3D analysis of
      nystagmus during peripheral vertiginous attacks was carried out. In comparison
      between the three components, the horizontal component had the largest ratio in
      each disease. Spontaneous nystagmus was directed toward the affected side in 3
      cases and to the opposite side in 15. In patients with Meniere's disease (MD),
      all subjects had horizontal and torsional components and had almost the same slow
      phase velocity in these two components. In patients with vestibular neuritis (VN)
      and Hunt's syndrome (HS), nystagmus was directed toward the opposite side.
      Furthermore, in VN, all subjects had an upward component, in addition to
      horizontal and torsional components. Inferring the focus from the character of
      nystagmus, it is speculated that the pathological changes are located in the
      entire inner ear in MD, whereas in VN the lesion is located in the horizontal and
      anterior semicircular canal or the superior vestibular nerve.

PMID- 9288246
TI  - Computed radiographic measurement of the dimensions of the vestibular aqueduct in
      Meniere's disease.
AB  - Lateral polytomography of the vestibular aqueduct by computed radiography was
      carried out in 30 normal subjects and 25 patients with Meniere's disease, 14 of
      whom had bilateral involvement. The vestibular aqueduct could be identified
      clearly not only in normal subjects but also in patients with Meniere's disease.
      Normal vestibular aqueducts were funnel-shaped or tubular, and the width of the
      external aperture was 6.0 mm on average. In contrast, a hypoplastic vestibular
      aqueduct with a narrow external aperture was often observed in patients with
      Meniere's disease. Especially, in affected ears of patients with unilateral
      Meniere's disease, the external aperture was very narrow; its mean width was 2.2
      mm. In these cases, the most common radiographic configuration of the vestibular
      aqueduct was filiform. Meanwhile bilateral Meniere's disease had a relatively
      wide external aperture compared with that of unilateral Meniere's disease,
      although a hypoplastic vestibular aqueduct was also observed in patients with
      bilateral Meniere's disease. As to the distribution of radiographic configuration
      types, bilateral Meniere's disease had almost the same distribution as in normal
      ears. From these results, it was concluded that a hypoplastic development of the
      vestibular aqueduct was based on the etiology of Meniere's disease, but general
      factors as well as a hypoplastic vestibular aqueduct seem to be responsible for
      bilateral involvement.

PMID- 9288247
TI  - Application of parasagittal surface coil MRI to otoneurological diagnosis.
AB  - Parasagittal surface coil magnetic resonance imaging (MRI) of the internal
      auditory canal and the inner ear was performed in patients with otoneurological
      diseases. T2-weighted fast spin-echo sequences, plain and enhanced T1-weighted
      sequences were used to examine the inner ear and the individual nerves in the
      internal auditory canal. Normal parasagittal images of the inner ear and the
      internal auditory canal and 4 patients with otoneurological disorders are
      presented. Precise location of the acoustic tumor was visualized and
      postoperative status of the internal auditory canal and the inner ear was
      assessed by the present method. The cochlear nerve was not identified in a
      patient with long-standing unilateral deafness. A follow-up study with MRI was
      performed in a patient with Meniere's disease who underwent endolymphatic-mastoid
      shunt surgery, showing gradual postoperative shrinkage of the shunted
      endolymphatic sac. The present method provides a new approach to the assessment
      of otoneurological disorders.

PMID- 9288248
TI  - Usefulness of magnetic resonance imaging in diagnosing vertebro-basilar
      insufficiency.
AB  - To estimate the usefulness of magnetic resonance imaging (MRI) in diagnosing
      vertebro-basilar insufficiency (VBI), 41 VBI patients with vertigo or dizziness
      and 26 subjects without vertigo or dizziness (as control) were examined by MRI.
      Sixty-eight percent of the VBI group and 12% of the control group showed a large
      difference between the right and the left vertebral artery diameter, the
      incidence being significantly higher in the VBI group. Thirty-nine percent of the
      VBI group and 12% of the control group had lacunar infarction in the brain stem,
      of which the incidence was significantly higher in the VBI group, MRI can be
      recommended to diagnose VBI providing information on both blood vessel disorder
      and ischemic changes in the brain.

PMID- 9288249
TI  - The prevalence of definite cases of Meniere's disease in the Hida and Nishikubiki
      districts of central Japan: a survey of relatively isolated areas of medical
      care.
AB  - In order to evaluate the prevalence of definite cases of Meniere's disease (MD),
      we performed a 1-year survey in 1994 of patients in the Hida and Nishikubiki
      districts, where a majority of the patients are thought to seek treatment at the
      medical facilities within these areas for geographical reasons. As a result of
      the cooperation of all ENT departments of the general hospitals and ENT clinics
      (general practitioners) in these districts, 67 patients were diagnosed as
      definite cases of MD according to the diagnostic criteria proposed by The
      Meniere's Disease Research Committee of Japan. Annual prevalence was estimated at
      36.6 per 100,000 population in the Hida district and at 21.4 per 100,000
      population in the Nishikubiki district, which is higher than those reported in
      previous Japanese surveys.

PMID- 9288251
TI  - Compensation after sudden loss of unilateral vestibular function and optokinetic
      after-nystagmus.
AB  - After unilateral labyrinthectomy or vestibular neurectomy, optokinetic after
      nystagmus (OKAN) to the ipsilateral side was abolished, then gradually recovered.
      We studied whether the compensation could be evaluated by observing OKAN.
      METHODS: Unilateral labyrinthectomy or vestibular neurectomy was performed under
      general anesthesia in cases of severe inner ear origin vertigo. Eye movements
      were recorded by electronystagmography (ENG), and the duration of OKAN was
      measured. RESULTS: The duration of OKAN to the ipsilateral side was shorter than
      that to the contralateral side (85%), the ipsilateral side was longer in 15%
      after labyrinthectomy. After vestibular neurectomy, the duration of OKAN to the
      ipsilateral side was shorter in 90%, and in 10% it became symmetrical.
      CONCLUSION: The stage of compensation after unilateral labyrinthectomy or
      vestibular neurectomy can be seen by measuring the duration of OKAN.

PMID- 9288250
TI  - Time series analysis of the course of Meniere's disease.
AB  - Subjective symptoms of Meniere's disease (vertiginous attacks, nonparoxysmal
      dizziness, tinnitus, hearing loss, headache, stiff neck, nausea etc.) were graded
      respectively according to severity (0-3 or 0-5) and were recorded daily by
      affected patients. These recordings, from 20 cases of Meniere's disease, were
      collected and analysed by an original program of time series analysis including
      autocorrelation, cross-correlation, daily sum of inner ear related factors and
      general factors, and their moving average. Cluster occurrence of dizzy spells in
      the active stage and a marked cross-correlation between inner ear factors and
      general factors were found to constitute a characteristic pattern in Meniere's
      disease in relation to its pathophysiology. Time series analysis was also useful
      for clinical decision-making, such as evaluation of the effect of treatment, and
      estimation of prognosis.

PMID- 9288252
TI  - Antidiuretic hormone and psychosomatic aspects in Meniere's disease.
AB  - We studied the relation between psychosomatic profiles of patients with Meniere's
      disease and antidiuretic hormone (ADH). For investigation of the psychosomatic
      aspects, we used the Cornell Medical Index (CMI), Yatabe-Guilford personality (Y
      G) test and the originally produced stress questionnaire. In Y-G test, patients
      with Meniere's disease are classified in normal group. In the CMI test, on the
      other hand, types III and IV were significantly more often observed in Meniere's
      disease than normal control (chi 2 test, p < 0.05). However, the CMI test results
      have no correlation to plasma ADH (p-ADH) levels. The survey of our original
      questionnaire revealed that stress has a close relationship to vertiginous
      attacks. Further, high p-ADH levels were significantly frequently observed in
      cases with stress compared with cases without stress (t-test, p < 0.05).

PMID- 9288253
TI  - Treatment of ipsilateral delayed endolymphatic hydrops.
AB  - Nine patients with ipsilateral delayed endolymphatic hydrops were treated. All
      cases were initially treated by conservative therapy using isosorbide or other
      drugs and 4 patients have been doing well without surgical intervention, though
      they occasionally have slight dizziness. Five patients required surgery to
      control vertigo. Three patients first underwent cochleosacculotomy to maintain
      the vestibular function in the diseased ear, but vertigo recurred after 6 months
      in all 3 cases. These 3 patients and another patient who wanted definitive
      treatment right from the start underwent transmastoid labyrinthectomy which
      resulted in complete control of vertigo. One patient received chorda tympani
      nerve section because he did not want his vestibule destroyed. After the nerve
      section, he has had no vertigo though sometimes dizziness. Transmastoid
      labyrinthectomy seems to be the best treatment for ipsilateral delayed
      endolymphatic hydrops.

PMID- 9288255
TI  - How common is recurrent acute otitis media?
AB  - To illustrate how the number of children with recurrent acute otitis media (RAOM)
      and the natural history of this condition vary according to the criterion used,
      different criteria were tested in a random sample of 2,411 children monitored for
      otitis media up to an average age of 22 months. The numbers of children
      fulfilling the criteria of at least 2, 3 and 4 episodes in 6 months were
      calculated and the natural history of otitis media during the following 6 months
      was examined among the children who had had a sufficient follow-up time and who
      had received no special prophylaxis. At least 2, 3 or 4 episodes in 6 months were
      experienced by 825 (34%), 375 (15%) and 118 (5%) children, respectively. During
      the 6 subsequent months after contracting the second, third or fourth episode, 5,
      4 and 5% of the infants developed chronic otitis media with effusion and an
      additional 10, 12 and 7% respectively, continued to have recurrent episodes
      without any special prophylaxis. In all, the proportion of children with
      recurrent episodes varied according to the criterion used. RAOM seemed to be a
      temporal phenomenon, however, and spontaneous recovery without any special
      prophylaxis was common with increasing age irrespective of the criterion used.

PMID- 9288254
TI  - Effects of vestibular rehabilitation on postural control.
AB  - We evaluated the effects of vestibular rehabilitation on postural instability in
      2 patients with unilateral and bilateral reduced vestibular function. Another
      patient with unilateral vestibular disorder was treated with drugs without
      vestibular rehabilitation. The outcome of postural control in these 3 patients
      was measured using an EquiTest. With this apparatus, improvement of postural
      stability and change of postural strategy were measured under the condition eyes
      closed and platform movement was dependent on the subject's anterior-posterior
      sway. The observations suggest that the vestibular rehabilitation had a positive
      effect not only on postural stability but also on postural strategy.

PMID- 9288256
TI  - Occurrence of otitis media in an arctic region.
AB  - The occurrence of otitis media (OM) was examined retrospectively in files at
      Longyearbyen Hospital, Svalbard, Norway during 1991-1994. Acute OM (AOM) with and
      without spontaneous drum perforation, secretory OM (SOM) and chronic OM (COM)
      with and without suppuration were registered, as were patient's sex, age, and
      climatic conditions. These findings were compared with weather observations
      obtained from the Norwegian Meteorological Institute, Tromso in the same period.
      Sixty-four percent of the OM patients registered were classified as AOM, 17%
      having a spontaneous drum perforation. Thirty percent suffered from SOM, whereas
      6% had COM. Forty percent of the patients were younger than 6 years. The
      distribution of OM cases during the year showed a peak during the spring,
      especially in May. Another minor peak was noted in September. Average daily
      temperature in the period was -5.6 degrees C, range -14 degrees C to +6 degrees
      C. Humidity and precipitation were fairly stable throughout the observation
      period 74% and 240 mm/year, respectively. OM is a common disease at Svalbard and
      is apparently related to seasonal shifts in temperature.

PMID- 9288257
TI  - Early acute otitis media: determined by exposure to respiratory pathogens.
AB  - The purpose of the present study is to assess the relationship between early
      acute otitis media (AOM) and exposure to respiratory pathogens mediated by
      siblings and day-care. A prospective cohort of 3,754 Norwegian children born in
      1992-93 was followed from birth through 12 months. One or more episodes of AOM
      had been experienced by 25% of the children before age one. Logistic regression
      analysis showed that siblings attending day-care is the most important risk
      factor for early AOM (ORadj = 1.9 (1.4-2.3)). The total number of children in the
      day-care setting is another determinant for early AOM (ORadj = 2.0 (1.4-2.6) in
      groups of 4 or more other children and ORadj = 1.3 (1.0-1.7) in groups of 1-3
      other children as compared with those who are cared for alone). Siblings who
      attend day-care and the number of children in the child's own day-care setting
      are the most important determinants for AOM the first year of life.

PMID- 9288258
TI  - Are there microbiological markers to predict recurrent acute otitis media?
AB  - The nasopharynx is a natural reservoir for several bacterial species, including
      Streptococcus pneumoniae and Haemophilus influenzae. Carriership is a potential
      mechanism for pathogenicity, since bacteria might invade the Eustachian tube and
      cause middle ear disease. Whether the pattern of nasopharyngeal colonization is
      different in infection prone vs healthy children is still a matter of
      controversy. In several studies it has been shown that H. influenzae is carried
      significantly more often in otitis-prone children compared with healthy control
      children. Colonization with H. influenzae in young children may be regarded as a
      candidate for a microbiological marker for recurrent episodes of acute otitis
      media.

PMID- 9288259
TI  - Bacteriological findings and persistence of middle ear effusion in otitis media
      with effusion.
AB  - The bacteriology of middle ear effusion (MEE) of asymptomatic otitis media with
      effusion (OME) was studied in 165 children, aged 5 months to 12 years, from the
      MEE samples obtained during tympanostomy under general anaesthesia in 1993-1994.
      MEE had persisted for 1 to 12 (mean 3.5) months. Major otitis pathogens (S.
      pneumoniae, H. Influenzae, B. catarrhalis and S. pyogenes) were cultured in 41%
      of the children under 2 years of age and in 17% of older children (p < 0.001).
      Respiratory infections and attacks of acute otitis media (AOM) during the last 6
      months were also more frequent in children younger than 2 years (p < 0.001). The
      proportion of S. pneumoniae (25%) and H. influenzae (38%), but not of other
      bacteria, was higher in the children with less than 2 months' persistence of MEE
      as compared with those with a longer duration (8% and 3%) (p < 0.01). After 2
      months, the occurrence of different bacteria remained relatively unchanged until
      6 months' persistence of MEE, and thereafter no pathogens were culturable. Among
      the children adenotomized earlier, the proportion of those with major otitis
      pathogens in MEE was 8% compared with 32% in non-adenotomized children (p =
      0.02). S. pneumoniae, B. catarrhalis or S. pyogenes were not culturable in any of
      the adenotomized children, while MEE grew them in 25% of the non-adenotomized
      children (p < 0.001). Since the MEE bacteriology of OME with less than 2 months'
      persistence resembles that of AOM, it may be that these cases represent a
      transitory phase between AOM and an established OME.

PMID- 9288260
TI  - Extended high frequency hearing and history of acute otitis media in 14-year-old
      children in Finland.
AB  - We studied the extended high frequency hearing of 573 white, urban, mean 13.8
      year-old unselected children in Tampere, Finland. All their ear-related morbidity
      had been recorded since their birth and they had been examined at the ages of 7
      months, 2 years, and some of them at 5 years. The extended high frequency
      audiometry was measured from 10 to 18 kHz, with 1 kHz steps, and the results were
      related to the number of attacks of acute otitis media (AOM) (0, 1-2, 3-7 and >
      or = 8) they had experienced. The mean pure tone hearing thresholds varied from
      10.7 dB at 10 kHz to 37.0 dB at 18 kHz in the right ears and between 11.6 dB at
      10 kHz and 37.4 dB at 18 kHz in the left ears. Among those with > or = 8 attacks
      of AOM the the thresholds were highest, the difference between them and each of
      the first 3 groups being statistically significant at 13 and 14 kHz. From 11 to
      16 kHz the same difference was significant between the last (> or = 8 AOM) and at
      least 2 of the first 3 AOM groups. Numerous attacks of AOM may have a harmful
      effect on high frequency hearing in the long term.

PMID- 9288261
TI  - Prognosis of acute otitis media. Factors associated with the development of
      recurrent acute otitis media.
AB  - Clinical factors associated with the development of recurrent acute otitis media
      (RAOM) (> or = 3 recurrences during 6 months' follow-up period) after acute
      otitis media (AOM) were analysed in 121 children aged 3 months to 7 years (median
      2 years 6 months). After AOM, 19 (16%) children had primary recurrence (pre
      treatment signs and symptoms firstly improved or cured, but worsened or recurred
      within 30 days' post-treatment) and 33 (27%) developed RAOM during 6 months'
      follow-up period. It seemed that children < 2 years of age (p = 0.04), children
      with bilateral disease (p = 0.007), strong infection status (p = 0.05), primary
      clinical failure (p = 0.04) and development of primary recurrence after AOM (p =
      0.001) were significantly related to the development of RAOM in univariate
      analysis, but only children < 2 years of age (OR 1.5, 95% CI 1.0-5.7, p = 0.04)
      and the development of primary recurrence (OR 5.1, 95% CI 1.8-14.1, p = 0.002)
      related to the development of RAOM in multivariate analysis. None of the bacteria
      cultured from middle ear effusion were related to the development of RAOM.

PMID- 9288263
TI  - Preconditioning the tympanic membrane: identification of cholesteatoma prone
      ears?
AB  - Preconditioning refers to changes in the mechanical properties of tissues due to
      repeated stress-strain experiments. Generally, after a number of cyclic
      deformation, a steady state is reached, where the experiment becomes repeatable,
      and the specimen is preconditioned. Tympanometric measurements of middle ear
      compliance also show increasing values for repeated trials until after 5 or 6
      measurements, where steady state is reached. However, in some normal cases with
      high compliance it has previously been found that the tympanic membrane is not
      always able to reach a steady state, but displays larger and larger compliance
      over trials. This property may be characterized as a decreased resistance against
      pressure loads, which may lead to retractions, atelectasis, and cholesteatomas.
      Preconditioning was investigated in a group of 21 patients with cholesteatomas.
      Due to perforations and discharge the contralateral ear was measured. Nine
      tympanometries were recorded in one sequence. The increase in compliance between
      trials showed a complete overlap with a group of 25 normal subjects. For both
      groups good repeatability between trials with insignificant effect of
      preconditioning can be obtained after 4 trials.

PMID- 9288262
TI  - Endoscopy of the middle ear structures.
AB  - The anatomical structures of the middle ear cleft were investigated with
      endoscopes of angle of view of 0 degree , 3 degrees and 90 degrees (1.7 mm in
      diameter). Temporal bone blocks donated by lately succumbed patients were studied
      3 times in random order. Forty-three anatomical structures of the middle ear
      cleft were chosen for inspection. The anatomical structures were counted and
      registered alternately at the time of endoscopy through 4 quadrants of the
      tympanic membrane. The study included 12,384 observation pieces. The results are
      presented in tables. The most suitable quadrant of the tympanic membrane and the
      angle of endoscope for optimal visualization are presented. The visualization is
      also presented by anatomical structure and by quadrants of the tympanic membrane.
      The authors' opinion for selection of the most convenient quadrant of the
      tympanic membrane and suitable angle of endoscope is presented. The majority of
      the anatomical structures could be visualized with either a 30 degrees or 90
      degrees endoscope. There were difficulties in observing the neck of the malleus,
      the head of the malleus and the lateral semicircular canal. There was no benefit
      from the use of a 0 degree angled endoscope in the visualization of the middle
      ear structures.

PMID- 9288264
TI  - Axial HRCT, two-dimensional and maximum intensity projection reconstructions in
      temporal bone lesions.
AB  - Axial and coronal high resolution computer tomography (HRCT) of the temporal bone
      is an important imaging technique to evaluate hearing loss. However the
      acquisition of the coronal imaging proves uncomfortable to the patient and is not
      always technically possible in old and ill patients. Clinical diagnoses of
      chronic otitis media, mastoiditis, cholesteatoma and cochlear otosclerosis in 10
      patients were studied on a third generation CT scanner. Axial 1 mm HRCT slices
      were acquired and the images were transferred to an Advantage Windows workstation
      where two-dimensional (2D) multiplanar and sagittal maximum intensity projection
      (MIP) reformations were performed. Our aim was to study the ability of this
      technique to identify several small structures of the temporal bone in various
      diseases. In all cases the finer structures of the temporal bone were identified
      in axial HRCT images. The tegmen tympani, atticus and the cochlea were best seen
      in the 2D coronal reconstructions. The aditus ad antrum, facial canal, vestibule
      and the semicircular canals were best seen on 2D sagittal reconstructions. The
      joints between the bony ossicles of the middle ear was best seen in the sagittal
      MIP reconstructions. Our results suggest that axial HRCT, 2D multiplanar and MIP
      reconstructions of the temporal bone produce images with sufficient diagnostic
      quality in patients with hearing loss.

PMID- 9288266
TI  - From posterior crus stapedectomy to 0.6 mm stapedotomy--towards reliability in
      otosclerosis surgery.
AB  - In the 1980s, in Oulu, clinical otosclerosis was primarily managed with posterior
      crus stapedectomy and in the 1990s, the method was changed to stapedotomy. This
      retrospective study was carried out to assess the results of different methods of
      stapes surgery in the hands of one surgeon. Subsequent primary stapes operations
      in 1989-1990 (91 operations including 74 posterior crus stapedectomies and 1
      Causse stapedotomy) and in 1993-1994 (117 operations including 1 posterior crus
      stapedectomy, 95 Causse pistons) were analysed. Changes in air and bone
      conduction thresholds were compared 5 weeks, 7 months and 19 or more months
      postoperatively. There was a significant difference in hearing (air-conduction-AC
      and bone-conduction-BC) in favor of Causse 0.6 mm teflon piston prostheses as
      compared to posterior crus stapedotomies at 7 months and 19 or more months.
      Likewise, the 4 kHz gain at the same time was also significantly better with
      Causse 0.6 mm all teflon piston. At 5 weeks, 81% of posterior crus stapedectomies
      and 78% of Causse stapedotomies had air conduction thresholds within 10 dB of
      preoperative bone conduction. However, at 7 months, the corresponding figures
      were 68% and 89%. Re-operations were performed in 26.7% posterior crus
      stapedectomies but only in 1% Causse 0.6 mm teflon piston stapedotomies. In the
      hands of the senior author (KL), the change from posterior crus stapedectomy
      technique to stapedotomy with 0.6 mm Causse teflon piston in primary stapes
      surgery proved to be successful. Surprisingly, the AC and BC hearing in the
      Causse stapedotomy group kept on improving during the follow-up.

PMID- 9288265
TI  - Computed tomography data based rapid prototyping model of the temporal bone
      before cochlear implant surgery.
AB  - Rapid prototyping (RP) technique allows automatic fabrication of 3D model parts.
      This method was applied to make a temporal bone model before cochlear implant
      surgery. A helical CT scan is used to acquire high resolution data from the
      middle and the inner ear of the patient. From the scanning data bone structures
      and soft tissues can be separated because their different grayscale pixel values.
      By using a guided image processing tool the desired parts of the anatomy can be
      extracted and 3D data created. The segmented data are processed to the form
      suitable for creating a high accuracy RP model. The RP model is made in the
      stereolithography (SLA) process by means of a computer guided HeCd laser beam
      inducing polymerisation of acrylic solution as it passes layer by layer over the
      surface of the polymer solution. In this prototype model the anatomy of the
      temporal bone can be clearly visualised, including, e.g., mastoid cells, tympanic
      cavity, bony canal of facial nerve, and round and oval windows. The inner ear
      spaces including vestibule, semicircular canals and cochlear turn are also
      shaped. The transparent acrylic material allows bonelike mechanical handling. The
      RP model can be dissected and used in individual surgical planning and simulation
      prior to cochlear implantation.

PMID- 9288267
TI  - Increase of diagnosed vestibular schwannoma in Denmark.
AB  - The incidence of acoustic neuroma/vestibular schwannoma (VS) in Denmark, with a
      population of approximately 5 million inhabitants was estimated in 3 periods:
      June 1976-June 1983, July 1983-June 1990 and July 1990-December 1995. The
      incidence of tumors increased from 7.8 tumors per million per year in the first
      period to 9.5 tumors per million per year in the second period. The figure of 12
      tumors per million per year is established in the third period. A significant
      increase of the newly diagnosed intracanalicular and small tumors, with an
      extracanalicular extension of 1-10 mm was observed in the third period compared
      with the first 2 periods. Correspondingly a decrease in the newly diagnosed giant
      tumors was noted in the last 2 periods compared with the first period.

PMID- 9288268
TI  - Non-surgical treatment of vestibular schwannoma patients.
AB  - The aim of the study was to evaluate the course of vestibular schwannoma (VS)
      when surgery was not attempted. The tumor may be slowly growing and surgery a
      risk for a patient. Twenty-eight patients out of 390 VS patients during years
      1981-1995 were primarily recommended a non-surgical treatment. Another 3 patients
      refused the operation. Altogether 23 women and 8 men were evaluated. Their age
      varied from 30.6 to 74.6 years (median 56.7 years). Tumor size varied from 5 to
      30 mm (median 15.0 mm) at the beginning of the follow-up. Patients symptoms,
      condition and other illnesses were recorded. Seven patients had neurofibromatosis
      2 (3 of them had one hearing ear), 2 had severe mental problems, 5 patients had
      their only hearing ear and 11 patients were not recommended an operation because
      of their age and other illnesses. Patients were controlled with MRI at intervals
      from 1 to 3 years. The follow-up time varied from 1 to 20 years (median 2.0
      years). The average tumor growth rate among unilateral VS patients was 0.035
      cm/year and among bilateral tumors the average tumor growth rate was 0.015
      cm/year. Two patients were later operated on, one 2 years after diagnosis because
      of the tumor growth and the other one 4 years after diagnosis-she had refused an
      operation earlier. Two patients could not be reached. Another patient had tumor
      growth but because of his illnesses he got a radiation beam instead of an
      operation. The majority of the patients could live fairly normal lives and
      required no treatment. Surgery is not the only alternative to VS patients. Wait
      and-see policy is also a good alternative to those who have high operation risk
      or who refuse an operation.

PMID- 9288269
TI  - The "toughening" phenomenon in rat's auditory organ.
AB  - In audiological "toughening" or "conditioning" phenomenon prior exposure to
      moderate noise reduces the extent of hearing deterioration caused by the
      subsequent exposure to traumatic test noise known to cause inner ear damage.
      "Toughening" has been demonstrated in many mammalian laboratory animals such as
      guinea pig and chinchilla but not in rat or mouse. Our aim was to study the
      occurrence of this phenomenon in the rat. Ninety-one white male Wistar rats were
      divided into four groups: unexposed control group (U, n = 10), "conditioning"
      only (C, n = 32), "conditioning" plus test noise (C + T, n = 36) and test noise
      only (T, n = 13). Groups C and C + T were "conditioned" for 10 hours with 4.0 kHz
      OBN between 55 and 95 dB sound pressure levels (SPLs). After 10 hours rest groups
      C + T and T were exposed to the same noise at 105 dB SPL for 13 hours. The
      hearing thresholds were determined by auditory brainstem response audiometry
      (ABR) either immediately after or 3 weeks after the exposures. After that the
      animals were sacrificed. The cochleas were removed and perilymphatically fixed
      and further processed for quantitative cytocochleograms. Both the temporary (TTS)
      and the permanent threshold shifts (PTS) were smaller in animals which had been
      "conditioned" prior exposure to traumatic noise. Yet only 95 dB SPL
      "conditioning" gave statistically significant difference (p < 0.05) in PTS. From
      our results we conclude that "conditioning" effect seems to be present also in
      the rat. However to confirm this, further experiments are needed. The mechanisms
      behind "conditioning" are still unknown and also to clarify them, further efforts
      are needed.

PMID- 9288270
TI  - Transtympanic electrocochleography in evaluation of cochleovestibular disorders.
AB  - We examined the electrocochleography (ECochG) parameters in patients suffering
      from Meniere's disease (n = 5) or other type of vertiginous disorder (n = 4).
      Fourteen ears were examined by introducing a needle electrode through the
      tympanic membrane to the promontorium. The summating potential (SP), action
      potential (AP) and the SP/AP ratio were measured from the alternating polarity
      click response, and the latency difference from the condensation and rarefaction
      click responses. These 2 patient groups differed from each other most clearly as
      to the audiometry results and the duration of symptoms. We also found differences
      in electrocochleographic results, especially in latency differences between the
      condensation and rarefaction click responses. Although the present material is
      small we conclude that transtympanic electrocochleography is a sensitive method
      to measure cochlear potentials, and might be a valuable addition in diagnosing
      patients suffering from various cochleovestibular disorders.

PMID- 9288271
TI  - A new analysis method for the evaluation of transient evoked otoacoustic
      emissions.
AB  - An analysis system with the Matlab 4.2 system with a filter bank is presented
      that provides graphically created 2D and 3D views of responses in the frequency,
      time and amplitude coordinates. Smoothed spectral and noise responses are
      presented. The start end and maximum TEOAE amplitude latencies are presented
      graphically and calculated numerically. The fast Fourier transformation (FFT),
      filter bank and wavelet transforms were developed and compared for the TEOAE
      analysis purposes.

PMID- 9288272
TI  - Hearing in 55 to 75 year old people in northern Finland--a comparison of two
      classifications of hearing impairment.
AB  - A total of 5,400 persons from different age groups was randomly selected from the
      population register for the study, and of the 1,620 55 to 75 year old persons
      invited, 1,233 attended the check-ups (76.1%). Air conduction pure tone
      thresholds were measured at the frequencies of 0.25, 0.5, 1, 2, 3, 4, 6 and 8
      kHz. The findings were interpreted according to both the EU and WHO
      classifications. According to the WHO classification, 1,046 subjects (85.0%) had
      normal hearing and 124 persons (10.1%) had a mild hearing impairment, 44 (3.6%) a
      moderate, 13 (1.1%) a severe and 3 (0.2%) had a profound hearing impairment.
      According to the EU classification, 758 subjects (61.6%) were found to have
      normal hearing, a mild impairment was observed in 363 persons (29.5%), a moderate
      hearing impairment in 96 (7.8%) and a severe impairment in 13 (1.1%) persons.
      None had a profound hearing impairment. The difference between these
      classifications is remarkable as is evident in even this small study. A thorough
      discussion on the role of different gradings for hearing is needed.

PMID- 9288273
TI  - New speech-in-noise test in different types of hearing impairment.
AB  - A new test was developed to assess speech recognition in noise. The test was
      designed to be run in a personal computer supplied with a sound card. One
      thousand disyllabic test words and noise were stored in digitized form on the
      hard disk of the computer. The measure given by this test is speech recognition
      threshold in noise (SRTN) corresponding to 50% recognition. The present series of
      180 cases with various hearing impairments and 39 controls were examined with
      speech-in-noise test and conventional audiometry. In keeping with earlier
      studies, the SRTN turned out to be significantly elevated in cases with
      sensorineural hearing impairment; this elevation was related to the grade of
      hearing impairment. On the other hand, no essential difference was seen between
      the SRTN values of subjects with mixed hearing impairment and persons with normal
      hearing.

PMID- 9288274
TI  - New computerized Finnish speech in noise test and binaural hearing.
AB  - Aided and unaided binaural versus monaural recognition of speech has been studied
      with more or less laborious methods when speech and noise sources are spatially
      separated. The efficacy of the new Finnish speech in noise test to show binaural
      advantage was evaluated in free field conditions. Thirteen subjects with normal
      hearing were tested measuring speech recognition thresholds in noise (SRTN) in
      anechoic chambre with different situations of spatial separation of speech and
      noise sources monaurally and binaurally. The noise source was fixed above the
      head (treating both ears similarly) and equidistant speech was delivered at
      different azimuths. SRTNs with mixed speech and noise without spatial separation
      served as normalizing reference. Differencies in SRTNs consistently followed the
      changing head and pinna shadow effects on the speech-to-noise ratio with a
      smaller binaural advantage. This new test seems to give quite economically the
      same results as those of previous more sophisticated investigations on speech
      recognition in free field situations.

PMID- 9288275
TI  - Non-specific effect of beettahistine on cochlear electrophysiology in guinea pig.
AB  - Beettahistine hydrochloride (BH) is reported to be beneficial in the treatment of
      certain type of vestibulo-cochlear disorders. Experimentally is shown that BH
      inhibits vestibular firing rate and improves cochlear blood flow by dilatating
      the larger feeding vessels. Both these effects are weak, and hardly can explain
      the clinical benefits reported for the drug. We investigated the effect of BH on
      the organ of Corti electrophysiology in vivo. Two microliters of 1, 2, 5 and 10%
      saline solutions of BH was applied (in increasing order) to the round window (RW)
      membrane in an anesthetized guinea pig (n = 5). Summating potential (SP), action
      potential (AP), and cochlear microphonics (CM) were recorded at 16 kHz frequency
      using RW Ag wire electrode. The repeated applications of BH with increasing
      concentrations produced a dose-dependent threshold shift in CAP. The I/O function
      for 20, 30, 40, 50, 60, 70, and 80 dB at 16 kHz indicated that there was a
      saturation before complete blockade of the responsiveness in all measured
      parameters. SP and CM changes nearly followed CAP changes. The changes recover
      during 2 hours follow-up period. Our findings indicate that BH affects the organ
      of Corti electrophysiology. That the drug effect saturates before a complete
      blockade suggests non-specific effect of BH on the organ of Corti structures and
      cochlear nerve.

PMID- 9288276
TI  - Effect of hyperbaric oxygen treatment on permanent threshold shift in acoustic
      trauma among rats.
AB  - Impulse noise from firearms is a common cause of acute acoustic trauma (AAT).
      Recently hyperbaric oxygen treatment has become available in many hospitals
      treating AAT. We exposed 39 Wistar rats to intense impulse noise of 60 shots from
      the assault rifle (162 dB SPL). After the exposure 15 animals were given
      hyperbaric oxygen treatment (HBO) by 10 treatment cycles of 90 minutes 100%
      oxygen in 0.25 MPa, one treatment cycle per day. Four weeks after the exposure
      the hearing thresholds were measured with auditory brainstem response audiometry
      at frequencies of 1.0, 2.0, 4.0, 6.0, 8.0 and 10.0 kHz. Characteristics for the
      resulting noise-induced hearing loss were large variations in its severity not
      only between animals, but also between the ears of a single animal. The largest
      permanent threshold shifts were found at 6.0, 8.0 and 10.0 kHz. Most of the HBO
      treated animals showed less threshold shift than the non-treated animals. The
      difference between the HBO group and the control group was only slightly
      statistically significant (p = 0.067).

PMID- 9288277
TI  - Azathioprine with cortisone in treatment of hearing loss in only hearing ear.
AB  - A sudden or progressive hearing loss in the only hearing ear is an otologic
      emergency, in which therapeutic possibilities are limited. We describe results of
      immunosuppressive therapy in 10 patients with one deafened ear either due to
      cochlear hydrops or Meniere's disease, who developed progressive or fluctuant
      hearing loss in the only hearing ear. The perilymphatic fistula was excluded with
      tympanoscopy. Azathioprine (25 mg t.i.d.) with prednisone (initial dose 20-40 mg
      with daily dose of 5-15 mg/day) was used. The hearing of 6 subjects responded to
      treatment. The initial pure tone audiogram (PTA) at speech frequencies of the
      "only hearing ear" was 57.3 dB HL with speech discrimination score (SDS) of 85%.
      The hearing improvement occurred successively within days or weeks. The average
      improvement of PTA was 22.4 dB HL after the mean treatment period of 5 weeks. In
      contralateral ear (the average PTA and SDS were 72.5 dB HL and 28%, respectively)
      the mean improvement in PTA was insignificant (4.4 dB). In 5 patients with
      vertigo it was improved in 3 cases. Cortisone alone or with combination of
      cyclophosphamide or ciclosporine was not effective in our hands.

PMID- 9288278
TI  - Comparison of carbogen inhalation and intravenous heparin infusion therapies in
      idiopathic sudden sensorineural hearing loss.
AB  - The effect of carbogen (5% carbon dioxide and 95% oxygen) inhalation and
      intravenous heparin on sudden sensorineural hearing loss was compared. Forty-four
      patients received the former, 43 the latter treatment, respectively. The patients
      were unselected patients of the clinic. The PTA (0.5-2.0 kHz) at the pretreatment
      stage was 62 dB in the heparin and 55 dB in the carbogen group. One month later
      the corresponding figures were 34 and 32 dB, the difference being statistically
      not significant. Thus neither of these methods proved superior in the treatment
      of sudden sensorineural hearing loss.

PMID- 9288279
TI  - Tinnitus treatment by transcutaneous nerve stimulation (TNS).
AB  - Twenty-six patients were treated with transcutaneous nervous stimulation (TNS)
      for tinnitus. Except for 3 normal hearing patients, all had cochlear hearing
      losses. Tinnitus disappeared in none, but diminished in 7 cases against 3 in 24
      nontreated controls. In the controls there were no reliefs in low-frequency
      tinnitus cases. One of these 7, who reported benefit initially, used the TNS
      system for several months. It seems that TNS is not as good as expected, but
      probably in cases where the tinnitus frequency is low and it disappears with TNS
      totally, the patients may use it.

PMID- 9288280
TI  - Radiotherapy enhanced ototoxicity of cisplatin in children.
AB  - We reviewed and re-examined 31 children (6 months-14 years at the time of
      diagnosis), who had been treated for a neoplasm in Turku University Central
      Hospital between 1989 and 1994. The children were divided into 3 groups according
      to the site of the neoplasm and the type of therapy. Group I included 13
      children, operated on for an intracranial tumor and received postoperative radio-
      and cisplatin-based chemotherapy. Group II included 14 children operated on for
      intracranial tumors and treated with radiotherapy, but not given chemotherapy.
      Group III included 4 children suffering from extracranial malignancies and they
      had received chemotherapy including cisplatin. The children in Group I had
      significantly worse hearing thresholds in the middle- and high-frequency range
      than children in Groups II and III. In a precise analysis of the different
      factors, no single dose of cisplatin, inner ear irradiation dose or totally to
      the central nervous system (CNS) received irradiation dose correlated to the
      detected hearing loss. However, multiple linear correlation analyses suggest a
      combined effect of radiotherapy plus cisplatin resulting in a high frequency
      hearing loss. This is in accordance with earlier random case reports, and
      supports the idea that radiotherapy should be considered cautiously in children
      treated with cisplatin for intracranial malignancies.

PMID- 9288281
TI  - Postural stability, neck proprioception and tension neck.
AB  - We examined whether tension neck (TN) may due to inadequate proprioceptive and
      vestibular activation of the cervico-collic reflex (CCR). CCR and vestibulospinal
      responses (VSRs) were recorded from 106 forest workers by stimulating the neck,
      lumbar or calf proprioceptors by vibration. The VSRs were recorded with
      posturography. TN occurred in 27 out of 106 subjects. The subjects with TN (48.5
      years) were older than those without TN (43.1). The mean body sway during quiet
      stance was the same in both groups during the neck stimulation. In subjects with
      tension neck stimulation of neck or lumbar proprioceptors caused excessive,
      unpredictable body excursion in the lateral and anteroposterior direction that
      continued after stimulation. Results from stimulation of lower limb
      proprioceptors did not significantly differ between the 2 groups. In logistic
      regression analysis a model to predict TN consisting of perstimulatory postural
      stability (odds ratio 1.4) and poststimulatory postural stability (odds ratio
      1.8) turned out to be statistically significant. The anatomical findings of CCR
      in the medulla oblongata suggest that neck muscle afferents control the posture
      and muscle activity of the neck. The erroneus facilitation of proprioception in
      TN subjects indicate that TN may be raised by inadequate facilitation of CCR.

PMID- 9288282
TI  - Phase difference of vestibulo-ocular reflex in head autorotation test.
AB  - In the head autorotation test (HART) gain is commonly used to determine the
      vestibulo-ocular reflex (VOR). The purpose of this work was to evaluate the
      relevance of phase (the phase difference between the eye and corresponding head
      movement) in describing the VOR. The phase was determined in 5 frequency bands in
      both degrees and milliseconds (ms) in 4 groups: 30 healthy adults, 15 elderly
      subjects, 37 vestibular schwannoma (VS) patients, and 35 Meniere's disease (MD)
      patients. In healthy adults and in MD patients the phase was close to nil in the
      frequency bands of 3 and 4 Hz. In elderly subjects phase lead was between 5.0 and
      15.5 ms in each frequency band. Patients with VS showed a phase lag of -4.2 to 
      7.6 ms. The mean phase of the elderly in the frequency band of 3 Hz differed
      statistically significantly from that of MD and VS patients, and in the frequency
      band of 4 Hz from that of healthy adults and VS patients. In summary, the elderly
      had phase lead and VS patients showed increased phase lag in the frequency bands
      higher than 2 Hz. The phase is useful parameter together with gain in evaluating
      VOR and it seems to change in aged subjects and in patients with permanent
      vestibular lesion.

PMID- 9288283
TI  - Benign recurrent vertigo--true or artificial diagnosis?
AB  - The etiology of many diseases involving vertigo is still unknown although the
      same etiologic factors have been suggested for several diseases. In most cases
      the diseases are diagnosed on the basis of exclusion-other possible causes being
      ruled out before the diagnosis can be confirmed. Benign recurrent vertigo (BRV)
      has been defined as spells of vertigo characteristic of Menieres disease without
      auditory or clinical neurologic symptoms and signs. The etiology of this
      condition is also unknown. BRV has been linked to migraine and viral diseases. In
      a prospective study we collected the clinical history and the signs and results
      of neurotologic and audiologic tests from 33 patients with a BRV diagnosis. The
      clinical characteristics truly mimicked the vertigo seen in Menieres disease. The
      concept of vestibular Menieres disease is not widely accepted, and without
      auditory signs BRV is the only diagnosis that can be given to these patients. In
      other studies up to 25% of the patients initially diagnosed with BRV subsequently
      developed another peripheral vestibular disorder. Until the etiology of diseases
      involving vertigo is more clearly understood, artificial diagnoses like BRV, must
      be accepted.

PMID- 9288284
TI  - Stability limits for visual feedback posturography in vestibular rehabilitation.
AB  - Vestibular rehabilitation therapy (VRT) is used to enhance compensation after
      peripheral vestibular lesion. In visual feedback posturography (VFP) a patient
      can practice postural control actively on a force platform and progress in the
      VRT can be objectively measured. The aim of the study was to determine normative
      values for stability limits (SL) in the VFP. Eleven healthy subjects were
      measured with force platform in visual feedback condition. Subjects were
      instructed to move their center of gravity (COG) marker to given targets, which
      were displayed on a computer screen in front of them. Target distance from the
      center of the platform was increased step by step to determine the SL in 8
      directions. Hit delays (HD) to the targets and hold percentages (HP) within the
      targets were measured to quantify the difficulty of the individual targets as a
      function of subject's shoe size. With fixed feet position the SL in anterior
      direction increased 1.2 times the absolute increase in shoe length. An almost
      similar increase was found in anterolateral direction. The knowledge of the
      mechanical SL is important, because targets near SL should be avoided for safety
      reasons.

PMID- 9288285
TI  - Changes in vestibulo-ocular reflex of elderly people.
AB  - Dizziness is a common symptom in elderly people. Head autorotation test (HART)
      has earlier shown no significant vestibulo-ocular reflex (VOR) disturbances in
      healthy elderly subjects. We used our recently developed HART to determine VOR in
      14 elderly volunteers without otoneurological diseases and sedative medications.
      Gain and phase were determined in 5 frequency bands from 0.5 to 5 Hz. The gain of
      the elderly was significantly increased to 1.11-1.27 in the frequency range of 3
      5 Hz compared with the controls. The phase lead of 7-8 degrees in the frequency
      bands of 2 and 4 Hz differed significantly from normative values of the controls.
      The percentage of the elderly to reach high-frequency head movements was
      diminished to 50% in the frequency band of 3 Hz and to 36% in the frequency band
      of 4 Hz (controls 100% and 95%, respectively). The individual HART results were
      abnormal in 86% of the elderly. The high-frequency VOR of the elderly was
      inaccurate in magnitude and timing. More than half of aged subjects were not able
      to generate voluntary fast head movements. These findings may explain the high
      prevalence of dizziness and falls in elderly subjects.

PMID- 9288286
TI  - Prognostication of Bell's palsy using transcranial magnetic stimulation.
AB  - Transcranial magnetic stimulation (TMS) provides a method to noninvasive
      excitation of the facial nerve in its intracranial segment close to the internal
      acoustic meatus. Thus, the site of facial nerve activation with TMS is proximal
      to or within the site of the lesion in Bell's palsy. To evaluate the prognostic
      capability of TMS in unilateral Bell's palsy we examined 137 patients with this
      method, and compared the results with electroneuronography (ENoG). Within 0-4
      days from the onset of palsy, the patients with elicitable TMS responses
      recovered better than those in whom TMS responses were not elicitable. If TMS was
      performed 5-9 days or 10-28 days after the onset of palsy, it did not provide any
      prognostic information. Based on amplitude side-to-side differences, ENoG did not
      contribute prognostic information during the first 9 days from the onset of
      palsy. Later on, 10-28 days after the onset of palsy, ENoG showed an increased
      capability to discriminate the patients with poor prognosis. Thus, elicitable
      facial motor response with TMS predicts good prognosis of Bell's palsy at an
      early stage whereas poor response with ENoG predicts less favorable prognosis at
      a later stage.

PMID- 9288287
TI  - Pediatric facial paralysis--a spirochetal infection with good prognosis?
AB  - The aim of the study was to investigate the possible signs of chronic spirochetal
      infection in 27 children with a history of facial paralysis with onset of
      symptoms during May-October 1985-1993. These children had not been studied at the
      time of facial paralysis for possible Lyme borreliosis and none of these children
      had received antimicrobial therapy at that time. The patients were interviewed
      with special reference to symptoms and signs of Lyme borreliosis and thereafter
      examined clinically and with laboratory tests. None of the patients showed signs
      or symptoms of chronic Lyme borreliosis. One child-now a 14-year old girl-had a 4
      fold rise in serum Borrelia burgdorferi antibodies as a sign of a recent
      infection. According to our prospective studies on pediatric facial paralysis in
      Finland (over 50% of children presenting with facial paralysis during May-October
      have Lyme borreliosis), we have a reason to assume that at least some in our
      study group had a facial paralysis caused by Borrelia burgdorferi infection. The
      results of our study indicate that facial paralysis has a favorable prognosis and
      in short-term follow-up the children do not have symptoms or signs of chronic
      Lyme borreliosis.

PMID- 9288288
TI  - Hemangioblastoma and oculomotor pathology.
AB  - We examined voluntary eye movements of 20 ophtalmologically screened patients
      (mean age of 51 years) with operated hemangioblastoma (HAB) in the cerebellum.
      Constant and pseudo-random saccades and pseudo-random smooth pursuit eye movement
      (PRPEM) test (with 4 frequency combinations) were evaluated. As controls 38
      healthy subjects were examined. In the logistic regression analysis latency and
      accuracy of constant saccades were the best predictors for operated HAB with
      correct overall classification rate of 79.3%. Accuracy was worse and latency
      longer in operated HAB group than in control group. In pseudo-random saccades
      correct classification between the groups was achieved in 82.8% of all cases with
      latency and accuracy as predictors. In PRPEM test the best frequency combinations
      in differentiating operated HAB patients from controls were 0.25 and 0.425 Hz for
      gain, and 0.3 and 0.7 Hz for phase and gain, the correct overall classification
      rate being 73.3% in both cases. The characteristic changes in voluntary eye
      movements after removal of cerebellar hemangioblastoma seem to be insufficient
      timing of initiating the eye movement.

PMID- 9288289
TI  - Oculomotor pathology in Meniere's disease.
AB  - In this study data of voluntary eye movements 62 patients (mean age was 49.6
      years) with Meniere's disease and 38 healthy control subjects were examined.
      Pseudo-random smooth pursuit (PRPEM) tests were conducted with frequency
      combination of 0.25 and 0.425 Hz. Saccades at constant targets and pseudo
      randomly shifting targets were evaluated. In logistic regression analysis
      constant saccades correctly classified the cases in 57% as saccadic latency
      discriminating the groups best, latency being longer in Meniere group. In pseudo
      random saccades, correct classification was achieved in 75.4% of all cases as
      latency discriminating the groups best, and latency was longer in Meniere group.
      In PRPEM, correct classification was achieved in 65.3% of all cases as gain by
      amplitude (GA), discriminating the groups best, and GA was smaller in Meniere
      group. Pseudo-random saccade test is a demanding task and that may explain why a
      peripheral vestibular lesion may interfere visual tracking and scanning
      performance. Latency is the most vulnerable of parameters to be lesioned. Results
      indicate that a peripheral vestibular lesion influences the control of voluntary
      eye movements and may explain the complaints of visual targeting on objects that
      patients with Meniere's disease have.

PMID- 9288290
TI  - Neural networks in neurotologic expert systems.
AB  - Artificial intelligence donates new possibilities to neurotologic research.
      Neural networks are a computer-based reasoning method which can be applied in
      expert systems created for clinical decision support. Neural networks have been
      used in medical imaging, in medical signal processing and to analyze both
      clinical and laboratory data. Principally, neural networks simulate the function
      of the brain. They have to be taught to make correct decisions from the input
      data. This learning process can be either supervised or unsupervised. The
      decision making is based on mathematical transformations and it occurs on a
      hidden level. Calculations are made on parallel manner and the decision making
      simulates pattern recognition method. Neural networks suit well in medical
      problems which cannot be defined in simple rules. A drawback of neural networks
      is that the decisions are irrational and cannot be motivated to the user. Another
      problem is neural networks' difficulty to handle incomplete input data, i.e., how
      to define some default or expected values for unknown input parameters. In a
      complex medical area, which would require multilayered neural networks, the
      neural networks require a large amount of solved cases for the learning process.
      In our experience neural networks seem not suitable for diagnosing vertigo and a
      better choice would be either case-based reasoning or possibly genetic algorithms
      or a combination of these.

PMID- 9288291
TI  - Change in minimal cross sectional area using the new nasal dilator, "Airplus".
AB  - In 36 persons without nasal complaints nasal cavities were investigated using
      acoustic rhinometry (Rhin 2000), to study the effect of a nasal dilator (ND)
      named "Airplus". The minimal cross sectional area (MCA) of both the right and
      left side was assessed before and after application of the ND, and the total MCA
      was calculated as the sum of the right and left side. In 8 persons the MCA was
      measured before and after 2 applications of the ND. In 8 persons the MCA was
      measured before, immediately after and 2 hours after application of the ND. In
      trial one the median total MCA was 1.37 cm2 before and 1.96 cm2 after application
      of the ND. This corresponds to an increase of 43%, p < 0.000-01. In trial two the
      median total MCA was increased from 1.37 cm2 respectively 1.35 cm2 to 1.98 cm2
      respectively 2.01 cm3, an increase of 45% respectively 49%, p < 0.008 in both. In
      trial three the median total MCA was 1.21 cm2 before and 1.95 cm2 immediately
      after application and 1.93 cm2 after 2 hours. The increase was 61 and 59%, p <
      0.008 in both. The results show that the "Airplus" nasal dilator improves
      significantly the MCA, it was possible to reproduce the effect and it was stable
      in the recorded period.

PMID- 9288292
TI  - Nasal provocation test in the diagnostics of hairdressers' occupational rhinitis.
AB  - Hairdressers are exposed daily at their work to many different hair chemicals and
      dandruff. The work-related nasal symptoms are common, especially with hair
      bleaching and striping. There are some reports on hairdressers asthma, but
      publications concerning occupational rhinitis among hairdressers are very few.
      The purpose of this study is to investigate the work-related rhinitis symptoms of
      hairdressers, and to study whether nasal provocation tests (NPTs) can be applied
      in diagnostics. The study subjects were 40 hairdressers having work-related
      rhinitis symptoms. Detailed work and exposure histories and work-related symptoms
      were inquired of using a questionnaire. Prick tests were done. Altogether 142
      NPTs were done: 40 placebo, 36 dandruff, 35 ammonium persulphate (APS), and 31
      ammonium thioglycolate (ATG). To register the nasal response rhinorrhea and nasal
      blockage were scored. In 3 allergen NPTs there was an essential change in the
      nasal status: in 2 APS and in 1 dandruff tests. Three patients were diagnosed as
      having an occupational rhinitis. The low number of positive reactions in NPTs and
      few positive reactions in skin prick tests verified that immediate allergy caused
      by hairdressers' work substances is uncommon. However, in cases of clear work
      related rhinitis, there is a need to perform examinations to find the probable
      allergy.

PMID- 9288293
TI  - Ciliary ultrastructure in experimental sinusitis.
AB  - Ultrastructure of respiratory cilia was observed in experimental sinusitis of
      rabbit maxillary sinuses. Sinus mucosa of 15 rabbits was inoculated with
      Streptococcus pneumonia bacteria and of 16 rabbits with Bacteroides fragilis
      bacteria. Specimens were taken during 12 weeks' observation time and they were
      studied by transmission electron microscopy from the cross-sections. A special
      emphasis was paid to the number of cilia, the ciliary orientation, the tubular
      anomalies, the presence of dynein arms and the compound cilia. It seems likely
      that pneumococcal sinusitis is a more toxic infection to the epithelium causing
      loss of ciliated cells and cilia than B. fragilis infection. In anaerobic
      infection ciliary ultrastructure remains normal and dynein arms as well as normal
      tubular ultrastructure were seen even after 12 weeks' infection.

PMID- 9288294
TI  - Clinical relevance of tubulus anomalies and compound cilia.
AB  - Transmission electron microscopy (TEM) from nasal mucosa and nasal mucociliary
      transport rate (MTR) with a radio-isotopic method were examined in 144 patients
      with various respiratory symptoms. Examinations were not performed during acute
      infections. In cases of increased amount of tubulus anomalies: nasal MTR was not
      significantly slower than in other patients, the disorientation of ciliary beat
      direction was significantly larger, there was no connection with increased amount
      of compound cilia and there was no correlation to any specific symptom or
      respiratory disease. In cases of increased amount of compound cilia: nasal MTR
      did not differ from other patients and the disorientation of ciliary beat
      direction did not differ from other patients. In a follow-up study of 76 patients
      5-11 years (mean 9.3 years) later the amount of tubulus anomalies and compound
      cilia had changed in most patients. In patients with less symptoms at the follow
      up than primarily, there was a non-significant tendency to have less tubulus
      anomalies, too, but no change in the amount of compound cilia. The amount of
      tubulus anomalies and compound cilia is not stable. Their number can either
      increase or decrease during a follow-up. Tubulus anomalies are non-specific and
      probably secondary changes of minor clinical importance and compound cilia would
      seem to be quite irrelevant findings in the ultrastructural evaluation of
      respiratory cilia.

PMID- 9288296
TI  - An ultrasound device in the diagnosis of acute maxillary sinusitis.
AB  - This multicenter study comprised 161 consecutive and unselected patients with
      suspected acute maxillary sinusitis (AMS). Altogether 322 maxillary sinuses were
      examined radiologically and by untrasound device (US). Of these, 234 antra were
      punctured, aspirated and irrigated. The volume of secretion coming out by
      irrigation was evaluated. The results of US, x-ray and irrigation were compared.
      For US, the proportion of correct positive results was 82.7% when the secretion
      volume was heavy, 78.6% when the secretion volume was moderate and 84.3% when the
      secretion volume was slight. When US finding was compared with the puncture
      result, the US gave false positive results in 8% of the cases and false negative
      results in 18.5% of the cases. Out of 187 positive irrigation findings,
      radiographs revealed fluid retention in 99 cases (score 3-6) (53%). Similarly, 11
      radiographs showed fluid retention in 47 cases of negative irrigation findings
      (23.4%). Statistical calculation shows that both US and radiology were equally
      reliable in diagnosing fluid retention and sinusitis, when the results are
      compared with the findings of the sinus puncture. US and radiology gave false
      positive findings almost equally (p > 0.05). On the other hand, when the volume
      of secretion was slight (< 1 ml), US gave a fluid echo finding more often than
      radiology showed fluid retention.

PMID- 9288295
TI  - Do simple laboratory tests help in etiologic diagnosis in acute maxillary
      sinusitis?
AB  - The aim of the present study was to evaluate whether the results of such simple
      hematologic tests as erythrocyte sedimentation rate (ESR), white blood cell count
      (WBC) and C-reactive protein (CRP) could give any useful information about the
      causative agents in 176 patients with acute maxillary sinusitis (AMS). The great
      majority of tests (82%) showed values which were within normal limits. This may
      be due to the fact that 22% of AMS cases were culture negative for bacteria and
      about 60% of culture positive cases had Haemophilus influenzae as the etiologic
      agent. Significantly raised test values were seen in connection with
      Streptococcus pyogenes in the majority of cases, less frequently with
      Streptococcus pneumoniae and rarely with Haemophilus influenzae. We conclude that
      none of the evaluated routine blood tests are particularly sensitive indicators
      of the specific etiology of AMS in general. However, elevated CRP values (> 40
      mg/l) associated with AMS should alert the physician to the suspicion of
      Streptococcus pyogenes or Streptococcus pneumoniae in etiology, since both, if
      left untreated, may lead to sinus empyema. With CRP or other evaluated tests
      Haemophilus influenzae- or Branhamella catarrhalis-positive AMS cannot be
      distinguished from a purely viral disease.

PMID- 9288297
TI  - Radiological findings in the maxillary sinuses of symptomless young men.
AB  - The maxillary sinuses were examined radiologically by occipitomental projection
      (Waters' view) in 404 conscripts without any symptoms of sinusitis. Abnormalities
      were found in 188 (23.3%) of all 808 sinuses, the most common being mucosal
      thickening of > 6 mm (12.3% of the sinuses), cysts or polyps (7.2%), and
      completely opacified sinus (3.3%). Normal x-ray findings were more common in the
      conscripts examined during the summer months and mucosal thickening was more
      frequently encountered in winter than in summer. Nasal bacteria were studied in
      100 cases. Findings of normal bacterial flora and of pathogenic bacteria were
      equally frequent among subjects with normal sinus x-ray (score 0 and 1) and
      subjects with severe abnormalities (scores 3-6), but mucosal cysts (score 2) was
      more often combined with pathogens in the nose. Mucosal thickening was more often
      observed in non-allergic than in allergic persons; thus allergy did not seem to
      increase radiological abnormalities. Of young men engaged in outdoor activities,
      about one fifth seem to have significant chronic mucous membrane abnormalities in
      the maxillary antra without clinical symptoms. In 1-2% of cases secretion is
      detected in the maxillary sinus indicating a subclinical sinusitis.

PMID- 9288299
TI  - Bacteriological evaluation of 194 adult patients with acute frontal sinusitis and
      findings of simultaneous maxillary sinusitis.
AB  - In a prospective study bacteriological findings from frontal and maxillary sinus
      secretes were analyzed. Frontal sinus trephination was performed to 103 and
      maxillary irrigation to 192 patients. Main pathogens in the frontal as well as in
      the maxillary sinus secretes were Haemophilus influenzae and Streptococcus
      pneumoniae. beta-lactamase production of H. influenzae was found in 17% of
      frontal and in 16% of maxillary sinus samples. Bacteriological findings were
      supported by the staining results. The portion of anaerobic pathogens in cultures
      were poor, though Bacteroides fragilis antigen was detected in 8 frontal and 6
      maxillary sinus samples. The acute frontal sinusitis should be treated with
      respective antibiotics. Complications seem not to develop in the acute phase and
      the disease can primarily be treated conservatively. It should however be
      controlled properly to avoid prolonged disease and late complications.

PMID- 9288298
TI  - Immunoglobulin-coated bacteria in effusions obtained during chronic maxillary
      sinusitis.
AB  - Local protection of the maxillary sinuses against bacterial invasion takes both
      specific and non-specific forms. The present study is intended to evaluate the
      participation of the specific protective factors, immunoglobulins IgG, secretory
      IgA, IgM and complement, in protecting the maxillary sinuses during chronic
      maxillary sinusitis (CMS). We collected 47 sinus effusion samples from 37
      patients (17 male, 20 female) with current CMS of at least 3 months' duration.
      Patients' ages ranged from 3 to 80 years. The effusion material was subjected to
      qualitative and quantitative bacteriological analyses, while bacterial coating
      with IgG, SIgA, IgM and C3b was determined using an immunofluorescence technique.
      Detectable bacteria were harboured by 55% of the samples, the most common species
      being Moraxella catarrhalis, Streptococcus pneumoniae and Staphylococcus aureus.
      The bacterial counts ranged from 0 to 10(9) per ml effusion. Half of the samples
      hosting detectable bacteria showed microorganisms coated with protective
      immunoglobulins. Antibacterial factors had completely eradicated the
      microorganisms in 45% of the CMS cases and coated the organisms with specific
      immunoglobulins in a further 28%.

PMID- 9288300
TI  - Bacterial findings in acute maxillary sinusitis--European study.
AB  - Bacteriology of acute maxillary sinusitis was studied in 569 patients in 16
      centers of 6 countries located throughout Europe during 1992-1994 by ENT
      specialists. Patients with symptoms of acute sinusitis lasting less than 3 weeks
      with ongoing purulent nasal discharge were included. Diagnosis was verified by
      sinus x-ray or ultrasonography and a positive aspiration finding in maxillary
      sinus puncture. One or more pathogens were isolated from the maxillary sinus
      aspirates of 375 (66%) patients. Fifty-six percent of patients harboured 1
      pathogen and 10% multiple pathogenic organisms, respectively. Haemophilus
      influenzae was the most common pathogen isolated (148 isolates), occurring as a
      single pathogen in 14% of the patients. The occurrence of H. influenzae was
      highest in Finnish military hospital patients (43-48%), as compared with the non
      military Finnish patients (9-11%) or to patients from other European centers
      (mean 13%). H. influenzae was more frequently beta-lactamase positive in other
      European centers (22%) than in Finnish centers (7%). Streptococcus pneumoniae was
      the most common pathogen isolated in other European centers (20%) but second most
      common in Finnish centers (13%). Moraxella catarrhalis occurred at quite similar
      frequency among Finnish centers (9-14%), but clearly less often in other centers
      (mean 4%). S. aureus, which in acute maxillary sinusitis is regarded as a
      contaminant from the nasal cavity, was more prevalent in other European centers
      (12%) than in Finnish centers (4%). In patients with acute maxillary sinusitis
      reliable bacteriological samples should be taken by antral aspiration directly
      from the diseased sinus.

PMID- 9288301
TI  - Humoral responses to bovine dust in dairy farmers with allergic rhinitis.
AB  - During the indoor cattle feeding season, dairy farmers are continuously exposed
      to allergenic bovine-derived materials for a long time every year. Limited
      information is available about the dynamics of exposed people's antibody
      responses under the influence of this kind of exposure. In this study, the level
      of antibodies to bovine epithelial antigen (BEA) was found to reflect the level
      of clinical allergy. On the other hand, the level of immunoglobulin (Ig)E, IgA
      and IgG antibodies to bovine urinary antigen (BUA) was lower in the group of
      bovine-allergic farmers than among other farmers. It was concluded that
      antibodies to different allergen extracts reflect different phenomena. Antibodies
      to BEA seem to be associated more with allergic symptoms, where as anti-BUA
      antibodies might reflect the level of bovine exposure. The indoor cattle feeding
      season did not cause any major changes in dairy farmers' humoral responses. The
      continued allergen exposure did not increase the level of sensitization as
      determined by antibody responses.

PMID- 9288302
TI  - Functional vs. radical maxillary surgery. Failures after functional endoscopic
      sinus surgery.
AB  - Randomized FES or Caldwell-Luc (C-L) operations were performed in 150 patients
      suffering from chronic maxillary sinusitis during 1987-1989. Follow-up
      examination was done for 143 patients (95%) 1 year postoperatively. Although 15
      patients had already deceased, questionnaires were obtained from 128 patients
      (85%) 5-9 years after operation. One year after surgery 51% of the C-L patients
      and 77% of the FES patients reported no symptoms or distinct improvement in their
      global symptoms, whereas 5-9 years postoperatively 82% of the C-L and 76% of the
      FES patients reported this outcome, respectively. Thirteen C-L operated patients
      (18%) and 14 FES patients (20%) have been reoperated during 7-9 years follow-up.
      In most cases revision surgery was done for polyposis or maxillary sinusitis. In
      the long term, altogether 21 patients (28%), including 14 reoperated patients,
      were failures after FES. These included also 4 patients with global symptoms
      unchanged at late inquiry and 3 other patients, though getting better, reported
      unwillingness for FES operation if they had known the result beforehand.

PMID- 9288303
TI  - Endoscopic sinus surgery or Caldwell-Luc operation in the treatment of chronic
      and recurrent maxillary sinusitis.
AB  - The treatment of chronic and recurrent maxillary sinusitis has been changed in
      recent years. The radical Caldwell-Luc approach has increasingly been replaced by
      more conservative functional endoscopic sinus surgery (FESS). In the central
      hospital of Central Finland between 1991 and 1992, 260 patients (424 sinuses)
      suffering from chronic or recurrent maxillary sinusitis were operated on.
      Patients were classed into three groups according to the patient history of
      sinusitis. The plain sinus films (occipitomental projections) were evaluated.
      Complication rate and the need for reoperations were evaluated retrospectively
      after a mean follow-up time of 3.8 years. Patients in the Caldwell-Luc group had
      more serious disease than in the FESS or antrostomy group. The plain sinus films
      taken preoperatively showed more opacification in maxillary sinuses in the
      Caldwell-Luc group than in the FESS or antrostomy group. Complication rate was
      4.4% in the Caldwell-Luc group and 2.6% in the FESS group. No serious
      complications existed in the whole material. Patients treated with Caldwell-Luc
      operation in 1991 and 1992 needed reoperation in 7/96 cases (7.3%) and 3/63 cases
      (4.8%), respectively. In the FESS group, patients operated 1991 and 1992 needed
      reoperation in 3/11 cases (27%) and 13/72 cases (18%), respectively.

PMID- 9288304
TI  - Operative treatment of frontal sinusitis.
AB  - When the medical therapy fails trephination is the primary operation indicated in
      acute eroding sinusitis when drainage is necessary to avoid severe complications.
      In recent years also endoscopic transnasal surgery has been recommended for
      exenteration of the underlying disease in the ostiomeatal unit as well as for
      opening of the obstructed nasofrontal duct in acute phase of the disease. In
      Turku University Central Hospital endoscopic frontal sinus surgery is still
      reserved for cases with prolonged or delayed disease performed as a secondary
      operation after trephination and CT examination. Failures are common after these
      operations and both types of surgical treatment may be needed. Three percent of
      our patients developed a persistent chronic infection inside the frontal sinus.
      In these cases external osteoplastic approach is recommended. In these operations
      we have used bioactive glass as obliteration material with promising clinical
      results.

PMID- 9288305
TI  - Report on results of frontal sinus obliterations in Turku University Central
      Hospital 1977-1994.
AB  - When a sinusitis develops into a chronic stage, for which endoscopic sinus
      surgery is not radical or successful enough, we currently perform in our hospital
      obliteration of the infected frontal sinuses. The present study is a partly
      retrospective and partly prospective evaluation of the outcome of patients
      operated on by osteoplastic approach. Obliteration materials used during years
      1977-1994 have been ossar, collagen matrix and since 1990 bioactive glass.
      Although major differences between the obliteration materials could not be
      demonstrated the obliteration with bioactive glass has proven to be a safe and
      effective method for patients who did not show any improvement after endoscopic
      sinus surgery.

PMID- 9288306
TI  - Results of dacryocystorhinostomy in 96 patients.
AB  - Between years 1895 and 1995, 112 patients underwent dacryocystorhinostomy in the
      Department of Otorhinolaryngology at Tampere University Hospital. A questionnaire
      considering the recent symptoms of patients was sent to 108 patients. Four of the
      patients have died. Ninety-six patients returned the questionnaire. Seventy-nine
      (61 primary operations) lacrimal systems underwent dacryocystorhinostomy (DCR) by
      external approach (Toti) and 25 (23 primary operations) by transnasal approach
      (West). Mean follow-up time was 5 years and 8 months. In extranasal DCR group 13%
      (8/61) of patients required a re-operation and of the others 85% (45/53) were
      satisfied with the result and still chose the same operation. In transnasal
      surgery group 30% (7/23) of patients required a re-operation and of the others
      56% (9/16) were satisfied and still chose the same operation. Twelve extranasal
      DCR were made due to trauma or congenital deficiency and 67% of them reported
      relief of their symptoms. In both groups the results were significantly better if
      silicon tubes were introduced after operation between eye and nose to keep the
      lacrimal system open.

PMID- 9288307
TI  - Snoring children: factors predicting sleep apnea.
AB  - Many snoring children present obstructive symptoms according to their parents.
      The seriousness of the symptoms and the possibility of the obstructive sleep
      apnea syndrome (OSAS) in these children may be difficult to judge on the basis of
      the clinical findings and the patient's history only. In order to evaluate
      snoring children's relative risk (RR) to have OSAS, their symptoms and signs, as
      reported by the parents, and clinical findings were compared with the results of
      overnight polysomnography (PSG). An obstructive apnea index (AI) > or = 1 in PSG
      was regarded as the criterion for OSAS. The mean AI was 1.55 (range 0-15), and 29
      children had a pathological AI, while 49 had a normal PSG recording. Apneic
      episodes every night detected by the parents was the most important single risk
      factor for OSAS (RR 3.6, 95% confidence interval (CI) 1.7-7.7). The RR ratio
      decreased when apneas appeared less frequently, but any detected apnea was still
      a single risk factor (RR 1.4, CI 1.2-1.8). The other risk factors of night-time
      symptoms were constant snoring (RR 1.5, CI 1.0-2.1) and restless sleep (RR 2.1,
      CI 1.1-4.0). Of the daytime symptoms, absence of excessive sleepiness was a
      protective factor against OSAS (RR 0.3, CI 0.1-1.0). Previous adenoidectomy was
      found to be a risk factor (RR 1.7, CI 1.1-2.7), as was tonsillar enlargement (RR
      1.4, CI 1.1-1.8). These two findings suggest that the epipharyngeal space does
      not play a central role in the development of OSAS in children. OSAS cannot be
      reliably diagnosed without PSG, which is the most important examination for
      snoring children with obstructive symptoms. For clinical decisions, the
      consideration of risk factors is essential.

PMID- 9288308
TI  - The effect of nasal obstruction on outcomes of uvulopalatopharyngoplasty.
AB  - Nasal obstruction is considered an aggravating factor in some patients with
      obstructive sleep disorders. There are no previous reports about the effect of
      nasal obstruction on outcomes of uvulopalatopharyngoplasty (UPPP). The symptoms
      of 100 patients treated by UPPP in our hospital were analysed. Forty-nine of them
      were diagnosed as having obstructive sleep apnea syndrome (OSAS), as ODI 4 was >
      5. Nasal obstruction was measured using preoperative anterior active
      rhinomanometry. The degree of snoring and daytime sleepiness was evaluated using
      a questionnaire preoperatively and again 6-12 months after the operation. Snoring
      was relieved in 96% of all patients. Excessive daytime sleepiness improved in
      87%, which is also consistent with earlier good results. There was no significant
      difference in improvement of these symptoms in nonapneic snorers and in patients
      with OSAS. In the group of 10 patients with highest nasal airway resistance
      snoring was relieved in only 78% as compared with 98% in the others (p < 0.05).
      Also excessive daytime sleepiness was better relieved in the group of patent
      nasal airway, but this difference was not statistically significant. Nasal
      obstruction can effect the outcome of UPPP. Treatment of nasal obstruction should
      be considered in chronic snoring if snoring and excessive daytime sleepiness
      persist after UPPP.

PMID- 9288310
TI  - The effect of laser-uvulopalatopharyngoplasty on the nasal and nasopharyngeal
      volume measured with acoustic rhinometry.
AB  - Nasal breathing is considered as an important factor in sleep apnea and snoring,
      and nasal obstruction can lead to an increased respiratory resistance and to
      inflammatory reactions in the nasal mucosa. Uvulopalatopharyngoplasty is an
      effective treatment for sleep apnea and snoring. Different operation techniques
      with minor variations have been introduced during the last few years.
      Uvulopalatopharyngoplasty with laser technique (LUPPP) has made it possible to
      perform the operation in local anesthesia. Acoustic rhinometry is a new method
      for the evaluation of the nasal cavities and the nasopharynx. We measured the
      volume of nasal cavities and nasopharynx of 29 patients using acoustic rhinometry
      before and 6 months after the LUPPP operation. There was a tendency to a better
      nasal patency in the turbinate area, but no change was found in the
      nasopharyngeal volume. Acoustic rhinometry is a useful tool for measuring the
      turbinate area, and this part of the nasal cavities seems to be influenced by the
      LUPPP operation, maybe due to a better ventilation or reduction of the
      inflammation of the nose. However, technical and methodological improvements are
      needed before reliable measurements are achieved from the nasopharynx area.

PMID- 9288309
TI  - Sleep disorders in patients with severe nasal obstruction due to septal
      deviation.
AB  - The role of nasal obstruction in etiology of the sleep apnea disease is
      controversial in literature. Forty-six subjects (3 women, 43 men) with severe
      nasal obstruction due to septal deviation were evaluated. The examination
      included case history, clinical ORL examination by ENT specialist, rhinomanometry
      and whole night sleep recording (SCSB, oximetry, EKG). Mean age of the patients
      was 40.0 years (from 17 to 68 years) and body mass index 26.0 kg/m2 (from 20.3 to
      34.6 kg/m2). The chief complaint of the patients was a severe nasal obstruction.
      Thirty-one patients (67%) had also heavy disturbing snoring, and apnea periods
      during sleep were reported by 10 cases. The evaluation of the sleep recordings
      revealed 12 cases with partial upper airway obstruction (26%), 1 case with severe
      airway obstruction, 1 case with mixed type of obstructive apnea and 3 cases with
      periodic limb movements. Evaluation of the oxygen desaturation of the blood
      revealed only 6 cases with significant disturbance (pO2 below 90% level). As a
      final result we conclude that severe nasal obstruction can lead to breathing
      disturbance during sleep.

PMID- 9288311
TI  - Immediate histological changes in soft palate after uvulopalatopharyngoplasty
      with CO2, contact Nd:YAG or combined CO2 and Nd:YAG laser beams.
AB  - CO2, contact Nd:YAG and Combolaser (combined, simultaneous and coaxial CO2 +
      Nd:YAG laser beam) were used for uvulopalatopharyngoplasty (UPPP). It has been
      proposed that the combined beam geometry diminishes thermal damage to surrounding
      tissues when compared with single laser radiation. To study the extent of thermal
      tissue damage produced by the lasers, tissue samples for light (LM) and
      transmission electron microscopy (TEM) were taken from the surface of the
      resected area and 2 and 4 mm below the resection plane. The depth of tissue
      damage and coagulation was measured. The results showed no consistent differences
      in the inflammatory reactions or the amount and depth of tissue coagulation
      observed in samples taken immediately after the operation. The CO2 laser
      typically produced a carbonized and coagulated wound edge. Combolaser and contact
      Nd:YAG lasers generated slightly less charring but otherwise resembled each other
      with coagulated and vacuolized resecate margins. These results indicate that the
      beam geometry in Combolaser does not diminish thermal damage to surrounding
      tissues.

PMID- 9288312
TI  - Pharyngeal patency caused by stimulation of the hypoglossal nerve in anaesthesia
      relaxed patients.
AB  - Impaired function of the genioglossal muscle is the most frequent reason for
      upper airway obstruction during sleep. Functional electrical stimulation (FES) of
      the hypoglossal nerve may be used to push the tongue forward to release the
      obstruction. Anaesthesia-induced upper airway obstruction resembles the situation
      during obstructive sleep apnea (OSA) syndrome. In order to develop an implantable
      FES system for treatment of OSA, we stimulated the exposed hypoglossal nerve in 6
      patients undergoing radical cancer surgery of the head and neck region. Tongue
      movements during stimulation were video filmed and the amount of unobstructed
      airway achieved with stimulation was estimated using the adjacent intubation tube
      as reference. In every case, stimulation created an unobstructed airway, larger
      than the intubation tube.

PMID- 9288313
TI  - Identification of Streptococcus pyogenes on tonsillar epithelium during
      infection.
AB  - Epithelial cells were swabbed from the tonsillar surfaces of 5 patients with
      acute tonsillitis culture-positive for Streptococcus pyogenes. By using 10 nm
      gold particles conjugated to antiserum to S. pyogenes it was possible to trace
      the actual microorganisms when examined in a transmission electron microscope.
      The S. pyogenes bacteria, usually in pairs, were attached to the epithelial
      surface by their pili. The bacteria often formed a hollow in the epithelial cell
      surface. Coccus-shaped bacteria expressing positive affinity to immunogold
      labelled antiserum were intermingled with bacteria, often rods, having no
      affinity whatsoever to the antiserum. With the immunocytological technique
      outlined in this study it is possible to study more closely cellular/bacterial
      adhesion mechanisms.

PMID- 9288314
TI  - Etiological factors of laryngeal cancer.
AB  - In order to evaluate the etiological factors, all 318 cases of laryngeal cancer
      diagnosed during the period of 1962-91 in the Tampere University Hospital area
      with a population of 400,000 were reviewed. Among males the annual age-adjusted
      incidence decreased significantly from 7.1 to 2.3 per 100,000. No significant
      difference in the occurrence was found between urban and rural areas. In males
      the relative risk (RR) was significantly higher in the lower socio-economic
      groups. In both sexes smokers had significantly higher risk compared to non
      smokers. For male smokers RR was 15.5 (95% CI 10.0-25.4) and for female smokers
      12.4 (95% CI 3.9-39.5). Changes in smoking habits seem to be the most important
      factor contributing to the decreasing incidence of laryngeal cancer in Finland,
      but other factors like changes in dietary and sauna habits may also have some
      significance.

PMID- 9288315
TI  - Cancer of the nasopharynx in children and young adults in Scandinavia.
AB  - Reports have been published indicating an increase in the incidence of cancer in
      the head and neck, e.g. the tongue, in children and young adults under 40 years
      of age. In the present study the number of new cases of nasopharyngeal cancer in
      Scandinavia during the period 1958-1992 was reviewed in the respective national
      cancer registers. Altogether 3,675 patients were diagnosed with cancer of the
      nasopharynx. Of these, 371 or 10.1% were under 40 years of age at the time of
      diagnosis. Within this time period no increase was seen in the relative amount of
      young among nasopharynx cancer patients in Scandinavia. When considering the
      whole 35-year period the percentage of patients below 40 years varied between the
      countries from 7.5% to 18.3%. The majority of the cases in each country occurred
      in males, both among the young patients as well as in the older age groups.
      Malignant neoplasms of the nasopharynx are rare in Scandinavia. Both the relative
      and absolute amount of patients under 40 years of age at the time diagnosis was
      stable. No difference in the 5-year relative survival rates was seen between the
      patient group under 40 years when comparing it with all age groups combined.

PMID- 9288316
TI  - The evaluation and treatment of the neck in carcinoma of the oral cavity.
AB  - Locoregional recurrence is the most common cause of failure in the treatment of
      carcinoma in the oral cavity. The extent of the disease can be evaluated by
      inspection, endoscopy, palpation, computed tomography (CT), magnetic resonance
      imaging (MRI), and ultrasound (US). The treatment consists of surgery, radiation,
      and their combination. The purpose of this study was to evaluate the effect of
      imaging and active treatment of the neck in patients with oral cancer. Altogether
      31 consecutive patients with 32 squamous cell carcinomas in the oral cavity were
      included. Of the tumors, 5 were T1, 18 were T2, 5 were T3 and 4 were T4.
      According to CT and US findings, 19 of the patients had a normal lymph node
      status, whereas 12 patients had enlarged or rim-like enhanced lymph nodes in the
      neck. Preoperative radiotherapy to the primary site and the neck was given to all
      except 3 patients. Surgery was carried out in all except 4 patients. A neck
      dissection was performed in N-positive cases (n = 9) and electively in patients
      with a high risk of metastases (n = 10). The median follow-up time was 31 months,
      with the minimum of 11 months, or until death. Seventeen (55%) of the patients
      experienced a recurrence. In only 1 patient the recurrence appeared initially in
      the neck, whereas all others had a local recurrence. Later, a distant metastasis
      was found in 3 patients. The meticulous imaging and active treatment of the neck
      were successful since only one patient's disease recurred primarily in the neck.
      The high number of recurrencies at the primary site show the need for intensified
      therapy.

PMID- 9288317
TI  - Squamous cell carcinoma of the oral cavity: the results of the surgical and non
      surgical therapeutic modalities in a consecutive series of 156 patients treated
      in Copenhagen county.
AB  - A retrospective study on patients, treated for intraoral squamous cell carcinoma
      in Copenhagen county, is reported. The material included 156 patients, 66 females
      and 90 males. Age at diagnosis varied between 35 and 95 years with a mean of 65
      years. Mean age of females/males was 70/62 years. Twelve therapeutic modalities
      were performed; surgery, radiotherapy, chemotherapy and different combinations of
      these. Three and five years crude survival were 43% and 37%. Three and five years
      crude survival rates were 70% and 61% for patients in stage I, 39% and 32% for
      patients in stage II, 29% and 16% for patients in stage III and 19% and 17% for
      patients in stage IV. The results are similar to those achieved in other centers.
      Since no significant improvement has been noted in patient survival during the
      last 5-6 decades and since the therapeutic morbidity has not always been
      acceptable to the patients, other therapeutic principles such as the so-called
      minimal invasive therapy should be considered in future treatment of intraoral
      cancer.

PMID- 9288318
TI  - Identifying genetic changes associated with tumor progression in squamous cell
      carcinoma.
AB  - Tumor behavior is the result of specific genetic changes that alter gene
      expression. From our cytogenetic studies chromosome 18 loss emerged as a common
      genetic change in squamous carcinoma cell lines. In this report we summarize data
      that link loss of 18 to tumor progression and reduced survival, indicating that
      one or more tumor suppressor gene(s) are located on this chromosome. Tumors grown
      in vitro were karyotyped either as short-term or permanent cultures. Loss of
      chromosome 18 was measured by karyotype, decreased frequency of heterozygosity at
      the DCC locus, and loss of heterozygosity (LOH) for microsatellite repeat
      polymorphisms (MSRP). Loss of any part of chromosome 18 was observed in
      approximately 63% of cultured tumors. Primary and secondary tumors from the same
      individuals sometimes differed in loss of 18 indicating that this genetic change
      is associated with tumor progression. Heterozygosity for DCC was present in only
      3/19 cultured SCC (16%), compared with 68% (11/16) of blood samples from
      unrelated donors, which is consistent with LOH in roughly one half of the cases.
      Of 4 informative cases with normal and tumor tissue, LOH was observed in 2.
      Microsatellite analysis also shows loss of 18q in 55% of fresh tumors. Analysis
      of tumor tissue and cell lines from the same patient gave identical results.
      There was an excess of deaths from cancer in the group with 18 loss (20/25) when
      compared with the group without (5/15). Loss of chromosome 18 appears to be a
      marker of tumor progression in SCC. It is likely that mutation affecting DCC or
      another gene on 18 affects tumor growth or spread, leading to more rapid
      progression and reduced survival.

PMID- 9288319
TI  - The bcl-2 gene status of human head and neck cancer cell lines.
AB  - The bcl-2 oncogene was originally found in the translocation in a pre-B cell
      acute lymphocytic leukemia cell line. Since then a high expression of Bcl-2 has
      been found in many types of cancer. The bcl-2 gene encodes an intracellular
      membrane-associated protein. Overexpression of bcl-2 inhibits apoptosis induced
      by many drugs and radiation. In this study the bcl-2 gene status of 9 human head
      and neck squamous cell carcinoma cell lines was studied. Mutations of the bcl-2
      gene were studied at mRNA and DNA levels. The presence and abundance of the Bcl-2
      protein in cells were also investigated. In earlier studies the p53 tumour
      suppressor gene was screened for point mutations, and the radiosensitivity of
      these cell lines was measured. We were able to amplify bcl-2 cDNA from 5 of the 9
      cell lines, which shows that bcl-2 was expressed in these cells. No point
      mutations were found in the bcl-2 gene in any of these cell lines. Loss of
      heterozygosity was observed in 2 cell lines at the bcl-2 locus, and these cell
      lines had no detectable levels of bcl-2 mRNA or Bcl-2 protein. The Bcl-2 protein
      was abundant in the cell lines with the wild-type p53 gene, and these cell lines
      were radioresistant. The Bcl-2 protein was also found in many other cell lines in
      mitotic cells. It seems that cells expressing bcl-2 are radioresistant, and even
      functional p53 cannot induce apoptosis in these cells.

PMID- 9288320
TI  - p53 mutations in human head and neck cancer cell lines.
AB  - The p53 tumour suppressor gene is commonly mutated in human cancers. We performed
      a molecular analysis of the frequency and spectrum of p53 gene mutations in 40
      cell lines (23 from oral cavity tumours and 17 from larynx tumours) derived from
      33 patients with squamous cell carcinoma of the head and neck (SCCHN). Using PCR,
      SSCP, and sequence analysis, we detected the mutated p53 gene in 26 patients
      (79%); in 23 patients (70%) the wild-type allele of the p53 gene was deleted.
      Four patients had 2 p53 gene mutations each, and thus the total number of p53
      mutations observed was 30. Seven patients had 2 cell lines each, established from
      the primary and recurrent/metastatic tumour, and the status of the p53 gene
      (mutant or normal) was identical in both cell lines. Forty percent of the
      mutations were transitions, 33% transversions, and 27% deletions, insertions and
      other more complicated changes. In oral cavity tumours the predominant mutation
      type was G:C-->A:T transition at a CpG site (50% of mutations), and in larynx
      tumours the predominant type was G:C-->T:A transversion (50% of mutations). These
      suggest endogenous and exogenous factors in tumour etiology. The G:C-->T:A
      transversions in larynx tumours are probably associated with mutagenic components
      in the cigarette smoke, but the causative factor in G:C-->A:T transitions
      (apparent oxidative damage) remains to be identified.

PMID- 9288321
TI  - Squamous cell cancer cell lines: sensitivity to bleomycin and suitability for
      animal xenograft studies.
AB  - Bleomycin (BLM) is a natural antibiotic, toxic to dividing cells (G2/M-phase),
      also proven effective in squamous cell carcinomas (SCC). We have clinically shown
      that a short-range beta-emitting radionuclide combined to bleomycin (In-111-BLMC)
      is a tumor-targeting agent in SCCs. With higher radionuclide activities it may be
      possible to develop a more effective agent, to be tested in animal studies. Using
      a 96-well clonogenic assay we investigated three SCC cell lines, grown in our own
      laboratory. IC20, IC50 and IC90 values for BLM were determined. The UT-SCC-12A
      and UT-SCC-12B cells were originated from a primary tumor and a metastasis of the
      same patient. UT-SCC-12A cells were also inoculated subcutaneously into nude mice
      and the tumor growth was analysed. The IC50 value for UT-SCC-19A cell line was
      4.0 +/- 1.3 nM. UT-SCC-12A and UT-SCC-12B were both more resistant to BLM; IC50
      values were 14.2 +/- 2.8 nM and 13.0 +/- 1.1 nM, respectively. Within 35 days the
      weight of nude mice increased 2.8 +/- 0.6g. At 25 and 35 days after tumor
      inoculations the tumor volumes were 111 +/- 51 mm3 and 874 +/- 577 mm3,
      respectively. The calculated doubling time was 3.86 +/- 0.76 days. SCC cell lines
      demonstrate different sensitivity to BLM. Our SCC tumor xenograft model showed a
      rapid growth proper for radiochemotherapeutic studies using In-111-BLMC. The
      uptake of In-111-BLMC in vivo has been directly proportional to proliferation
      activity, and the tumors with high binding capacity could be predicted from
      animal model dose calculations.

PMID- 9288323
TI  - Microvascular free tissue transfers after preoperative irradiation in head and
      neck reconstructions.
AB  - Surgical reconstruction of large head and neck tumors involves great problems.
      Preoperative irradiation increases the risk of postoperative complications. The
      use of microvascular free flaps has definitive advantages over conventional
      reconstruction techniques and permits immediate preoperative high-dose radiation
      therapy. Eighty-eight patients, 55 (62%) men and 33 (38%) women, with head and
      neck tumors underwent microvascular reconstruction at the Turku University
      Central Hospital in 1985-1995; 77 of them were irradiated before surgery. All
      irradiated patients underwent primary reconstruction. The preoperative radiation
      dose was 50-65 Gy. The free tissue transfer was successful in 77 (88%) of the 88
      patients. The success rate was 87% in irradiated patients and 91% in
      nonirradiated patients. Free tissue transfers are suitable for one-stage
      reconstruction in selected patients such as those receiving high-dose
      preoperative irradiation. The transfer of microvascular free flaps to the head
      and neck has become the most common reconstruction method owing to its increasing
      success rates as well as its excellent esthetic and functional results.

PMID- 9288322
TI  - Microvascular free flaps in head and neck cancer surgery in Finland 1986-1995.
AB  - Microvascular free tissue transfer has in many cases replaced classic flap
      techniques and is now an established workhorse for head and neck reconstructions.
      In this retrospective study the over 300 patients, who had microvascular free
      flap reconstructions in head and neck cancer surgery in Finland during a 10-year
      period (1986-1995) were reviewed. The operations were performed in the University
      Hospitals by plastic surgeons, ENT specialists or maxillofacial surgeons. The
      cases consisted of defects resulting from resection of oral cavity tumors (63%),
      mid- or upper-face and skullbase tumors (20%) and hypopharyngo-esophageal tumors
      (17%). The series includes a wide range of flap types and analyses flap outcome
      and complications. A total of 313 cases was reconstructed by 317 flaps (forearm
      flaps 47%, latissimus dorsi flaps 19%, free jejunum or colon transfers 15%, free
      iliaca crest flaps 8% and other flaps 11%). Thrombosis of one of the vessels and
      haematoma were the most frequent causes of failure in microvascular free tissue
      transfer. A total flap necrosis occurred in 27 (8.5%) and a partial necrosis in
      12 (4%) patients. The most reliable flap in terms of survival was the radial
      forearm flap. The ever-improving success of microvascular free tissue transfer
      has made it a useful procedure for head and neck reconstructions. There is also a
      growing need for microvascular team surgery in the field of head and neck cancer
      therapy.

PMID- 9288324
TI  - Speech rehabilitation by Provox voice prosthesis combined with heat and moisture
      exchange filters.

PMID- 9288325
TI  - The probability of conception on different days of the cycle with respect to
      ovulation: an overview.
AB  - Several mathematical models have been developed over the past thirty years to
      investigate how the probability of conception changes on the different days of
      the cycle with respect to ovulation. A problem general to all models is to
      estimate the day of ovulation. Since the most fertile days are those close to
      ovulation, less precise estimates of this event will lead to less accurate
      estimates of the probability of conception on a given day of the cycle. Given
      that a reference point for ovulation is available, the first model considered
      conception as dependent only on the timing of intercourse. Conception was found
      to be most likely to occur on only six days in each cycle. However, the model is
      biologically unrealistic because it assumes that all ova can be fertilized and
      lead to a viable pregnancy. There are other factors that affect the probability
      of conception, including whether the ovum is viable or not. Recent models have
      extended the idea of cycle viability to allow for differences between cycles
      within couples and for the introduction of couple specific covariates. In a
      second group of models the probability of conception depends mainly on the time
      of intercourse and the survival times of sperm and ovum. A graphical summary of
      the results available in the literature is presented. Conception probabilities
      have been found to be significantly different from zero from five days before
      ovulation to the day of ovulation itself. On average, less than half of the
      cycles are viable in women, although recent studies suggest that different cycle
      viability between women should be taken into account. Survival times for sperm
      and the ovum have been estimated to be 1.4 days and 0.7 days, respectively. Sperm
      would have a 5% probability of surviving more than 4.4 days and a 1% probability
      of surviving more than 6.8 days.

PMID- 9288326
TI  - Model-based approaches to studying fertility and contraceptive efficacy.
AB  - Statistical methods recently developed to aid in identifying environmental
      exposures with reproductive toxicity can also be applied to trials of
      interventions undertaken specifically to impair fertility, i.e. methods of
      contraception. Although only applicable in a trial that includes a reliable
      benchmark for identifying the day of ovulation, the proposed measures of
      contraceptive efficacy derived from such a trial offer certain interpretive
      advantages over the more traditional approaches of evaluating contraceptives.
      Extensions of the same models also allow one to evaluate efficacy under any
      assumed pattern of imperfect use. One can also evaluate methods based on
      biomarkers for the fertile phase of the cycle, such as hydration of the cervical
      mucus, that may prove to be enormously helpful to couples who wish to use
      periodic abstinence as their method. In prospective studies of fertility, couples
      who occasionally use a barrier method should not be excluded from the study, but
      can be retained, without biasing the estimates for fertility parameters.

PMID- 9288327
TI  - Probability of conception on different days of the menstrual cycle: an ongoing
      exercise.
AB  - The design of the European Multicenter Study on the probabilities of conception
      in different days of the menstrual cycle is reviewed. Some results, based on part
      of the data, are presented. These can be summarized as follows: a) Estimates of
      the probabilities of conception are lower than the ones previously reported in
      the literature; b) A strong effect of the man's age on fecundability was found.
      No evidence of a similar impact of the woman's age was demonstrated; c) The
      number of days with 'most fertile' mucus and parity affect fecundability.

PMID- 9288328
TI  - Is male reproductive health at risk? Longitudinal semen analysis studies.

PMID- 9288329
TI  - Incidence and implications of altered semen quality on family planning.
AB  - Alterations in the expression of the human genome, or interference with its
      products, can be induced in the male reproductive system by chemicals mimicking
      or antagonizing naturally occurring hormones. Opportunities exist for disruption
      at the hypothalamus, pituitary and testis levels. Recent concerns generated by
      the increased incidence of testicular cancer, congenital anomalies of the male
      genitalia and possible alterations in human semen quality have been linked to the
      environment. The report by Carlsen in 1992 [1] suggested that semen quality has
      deteriorated over the past six decades. More recent reports suggest that the
      decline may be globally non-uniform and regional in nature. The effects of any
      such declines upon overall pregnancy rates are generally unknown, although some
      studies have attempted to address them. A preliminary review of the impact of a
      small decrease in sperm concentrations suggests that a directly measurable
      reduction in fecundity does not occur, but that future problems could be
      anticipated. Decrements in semen quality will alter the epidemiological
      probabilities of pregnancy due to coitus on different cycle days and may thereby
      change the duration of the fertile time. Current understanding of the
      implications of altered semen quality on relative fertility is not sufficient to
      change our current teaching and practice of NFP.

PMID- 9288331
TI  - Monitoring reproductive hormones to detect the fertile period: development of
      Persona--the first home use system.

PMID- 9288330
TI  - Prediction and detection of the fertile phase of the menstrual cycle: an
      overview.
AB  - Distinct means have been developed to answer an increasing demand and need for
      methods that can accurately predict and detect the fertile phase of the menstrual
      cycle and fit various indications and changing situations of women's reproductive
      life. Methods based on the detection of direct fertility markers, such as
      hormonal tests and ultrasound, are more objective and accurate than traditional
      markers based on indirect markers, but cost and dependence on supplies limit
      their application. Nevertheless, these methods could be used during a few cycles
      either as support in the teaching phase or in difficult cases and for specific
      indications. Likewise, some new devices designed to facilitate recording and
      calculation of fertility signals could be combined with clinical methods to
      improve prediction and detection of the fertile phase. Besides the search for new
      fertility markers and the development of new methods, the possibility of
      combining already existing methods would certainly improve use-effectiveness and
      acceptance.

PMID- 9288332
TI  - Analysis of pre-ovulatory changes in cervical mucus hydration and sperm
      penetrability.
AB  - Changes in cervical mucus occur during the proliferative phase of the menstrual
      cycle and are known to correlate with receptivity to sperm and to the endocrine
      milieu. Prior studies, however, have often lacked biological incisiveness and
      technical objectivity and precision. This study analyzed daily changes in mucus
      water content (hydration) prior to the LH surge (LH+0) in normal women, in
      relation to daily levels of serum LH, FSH, estradiol and progesterone, and to
      daily tests of sperm penetration of the mucus. Cervical mucus was studied for 12
      cycles in 10 ovulating women. Three to ten mucus specimens were collected per
      cycle, over the days LH-8 to LH+0. Each specimen was subjected to measurement of
      both water content (hydration) and penetration by spermatozoa from fresh
      specimens of normal human semen. For the latter, a new microscale assay was
      developed and applied, which was amenable to very small volumes of mucus. The new
      technique determines objective measures of both the numbers of penetrating sperm
      (motile and non-motile) and the distance penetrated by the forward most vanguard
      sperm. In these experiments, variations in semen quality were controlled by
      performing a companion penetration assay in an artificial 1.5% polyacrylamide
      gel. The patterns of change in mucus hydration varied quantitatively among women,
      with preovulatory baseline levels ranging from 93.8-96.5%. All normal cycles (as
      defined by endocrine profiles) displayed a significant increase in hydration over
      a one-day period occurring 3-4 days before the LH peak. The magnitude of this
      shift varied among women between 2 and 3% (absolute hydration), a distinction
      well within the precision of the hydration assay. This quantum increase in
      hydration was more pronounced than the corresponding increase in serum estradiol
      on the same day. The change in mucus hydration, and the associated increase in
      sperm penetrability, were more consistent among cycles than the changes in
      reproductive hormones. There was a strong but non-linear correlation between
      mucus hydration and sperm penetrability. Once the value of hydration rose above
      approximately 97.5%, there was a substantial increase in penetrability. This 'cut
      off point' in sperm penetrability was in the middle of the range of hydration
      values (across women) which preceded the quantum jump in hydration-which, itself,
      preceded the surge of LH. Hydration began to increase approximately 2 days before
      measurable increases in sperm penetration of the mucus in vitro. These results
      demonstrate that mucus hydration may be a valuable marker of the approach to
      ovulation and delineation of the fertile period. They also provide new methods
      for assessing sperm penetration into both large peri-ovulatory and very small
      samples of collected mucus.

PMID- 9288333
TI  - Natural family planning effectiveness: evaluating published reports.
AB  - OBJECTIVE: To equip the reader with the tools necessary to evaluate studies of
      natural family planning (NFP) effectiveness found in the literature and to make
      recommendations for future NFP effectiveness studies. DESIGN: Current standards
      to evaluate contraceptive method effectiveness are reviewed. A framework for
      evaluating reports on NFP is presented. RESULTS: Most NFP studies found in the
      literature are flawed in design and do not calculate pregnancy rates correctly.
      The results from the few well-designed studies are presented. DISCUSSION: Many
      factors influence NFP effectiveness, and these factors must be considered when
      evaluating published studies and designing future studies.

PMID- 9288334
TI  - Simplifying NFP: preliminary report of a pilot study of the 'collar' method in
      Brazil.
AB  - Natural methods of fertility regulation are acceptable in most cultures. Many
      couples worldwide do not wish to use contraceptives or do not have access to them
      but wish to limit their family size or lengthen the time between births. Barriers
      to expanding use of natural family planning (NFP) methods include a lack of
      providers who can teach NFP and a lack of time to teach and follow couples during
      the initial months of NFP use. If simple yet effective methods of NFP are
      available, then NFP could be introduced to a wider audience. Recently, calendar
      rules have been revised that use a set interval to identify fertile days. These
      new rules provide better coverage of fertile days and require less abstinence
      than the rules traditionally used with the calendar method. One of these new
      rules is being field tested in a pilot study in Brazil. Couples are asked to
      abstain from day 9-19 (inclusive) of the menstrual cycle, using a beaded necklace
      (the 'collar') as a mnemonic device. Focus groups with the teacher-monitors and
      in-depth interviews with female and male users were carried out to evaluate the
      acceptability of the 'collar' method. A preliminary analysis of these focus
      groups and interviews from the first site is presented.

PMID- 9288335
TI  - Alternatives to vaginal intercourse practiced during the fertile time among
      calendar method users in Ireland.
AB  - A pilot study was conducted in Ireland to test the effectiveness of the calendar
      method of contraception. A conservative rule was used, requiring on average 16
      days of abstinence per cycle. Among the 19 couples who entered into the study and
      were followed for up to seven cycles, there were no pregnancies. Since the length
      of abstinence was relatively long, we collected data to determine how couples
      expressed love and affection towards each other during those days when the woman
      was potentially fertile. We also collected data about barrier method use during
      the fertile time. We found that almost all couples gave each other hugs and
      kisses to show affection although couples were taught to abstain from vaginal
      intercourse during the fertile time. About one-third of the couples avoided
      genital contact, while about half reported using oral sex and/or frottage (body
      rubbing). Twice as many men reported using masturbation compared to women,
      although about half of the couples practiced mutual (partner) masturbation. In
      addition, about one-fifth of the couples used condoms during the fertile time in
      some cycles. These findings show that a variety of sexual expressions are used by
      couples when vaginal intercourse is to be avoided. Knowledge about these
      alternative sexual expressions may be important for couples who wish to engage in
      sexual activity and to avoid pregnancy.

PMID- 9288336
TI  - Natural family planning with and without barrier method use in the fertile phase:
      efficacy in relation to sexual behavior: a German prospective long-term study.
AB  - A large prospective long-term study with users of natural family planning (NFP)
      methods has been conducted to analyze the relation between unintended pregnancy
      rates and sexual behavior with special reference to barrier method use in the
      fertile phase. Seven hundred and fifty eight NFP beginners, 19-45 years of age,
      14870 cycles, 28 unintended pregnancies were studied. Of the couples, 54.2% use
      NFP only or predominantly and 45.9% use mixed methods (additional barrier method
      use in the fertile phase in 55.7% of the cycles). The overall pregnancy rate
      after 12 cycles of exposure is 2.2% according to the actuarial method. There is
      no significant difference between NFP users and mixed methods users and also no
      significant effect of duration of use in the first 5 years of exposure. During
      "perfect use" the pregnancy rate at 12 months is 0.63%. When only protected
      intercourse takes place in the fertile phase the pregnancy rate is 0.45%. The
      symptothermal method of NFP is most unforgiving for imperfect use (unprotected
      intercourse in the fertile phase). However, it is extremely effective when either
      abstinence or protected intercourse is used in the fertile phase.

PMID- 9288337
TI  - Natural family planning in New Zealand: a study of continuation rates and
      characteristics of users.
AB  - This study has determined long-term continuation rates of clients who attended
      clinics of the New Zealand Association of Natural Family Planning and became
      autonomous users. It has also identified factors which might influence the
      continuation of NFP use. A total of 509 female subjects, 452 of them with their
      male partners, were enrolled in the study at the beginning of clinic teaching.
      Once autonomous they were sent questionnaires at 6-monthly intervals for a period
      of 24 months. Time out was allowed for pregnancy. The number of female subjects
      entering the 2-year follow-up phase of the study was 406 (79.8%). Of these 164
      completed 2 years of use with 102 (20% of study entrants) using NFP and 62
      (12.2%) using fertility awareness in combination with a barrier method. Subjects
      for whom NFP was their first family planning method, who were Catholic or who
      gave religion as their reason for choosing NFP were more likely to continue long
      term use. The majority of subjects (> 90%) were highly satisfied with NFP use,
      with the most common reasons for satisfaction being self-awareness, freedom from
      drugs, naturalness and effectiveness. The difficulties reported related to
      abstinence and cycle interpretation.

PMID- 9288340
TI  - Pregnancy complications in natural family planning users.
AB  - A multicenter cohort study was designed to assess pregnancy outcome among natural
      family planning (NFP) users, and provide the opportunity to address complications
      in NFP users by planning status and by timing of conception with respect to day
      of ovulation. There were 877 singleton births in this sample. Complications
      evaluated were abnormal vaginal bleeding, urinary tract infection, vaginal
      infection, hypertension of pregnancy, proteinuria, glycosuria, and anemia. There
      was no significant difference in the mean age, number of prenatal visits or birth
      weight among optimally and non-optimally timed pregnancies or for planned and
      unplanned pregnancies. There were higher incidences of "parity 2 or more" and
      current smokers in the non-optimally timed pregnancies and lower incidences of
      prior pregnancy loss and "currently employed" in the non-optimally timed
      pregnancies. There was little difference in pregnancy complications with respect
      to pregnancy timing, with the exception of a significant increased risk of
      vaginal bleeding late in pregnancy among non-optimally timed conceptions (11.5%)
      compared to optimally timed pregnancies (5.2%, RR = 2.2, 95% CI 1.3-3.7). More
      differences were observed in pregnancy complication rates by planning status.
      Unplanned pregnancies were associated with significantly more late pregnancy
      bleeding, vaginal infections, proteinuria, glycosuria and medication use than
      planned pregnancies. Unplanned pregnancies had lower incidences of maternal
      anemia. Complications of pregnancy were low in this NFP population, irrespective
      of planned versus unplanned status. Women with planned pregnancies had even fewer
      complications during pregnancy than women with unplanned conceptions, suggesting
      that women using NFP to plan their reproduction may be at particularly low risk.

PMID- 9288338
TI  - Pregnancy outcome in natural family planning users: cohort and case-control
      studies evaluating safety.
AB  - Conceptions involving aging gametes are of relevance to natural family planning
      (NFP) because women using NFP to avoid pregnancy abstain from intercourse during
      the fertile time of the cycle. To help verify the safety of pregnancies occurring
      among NFP practitioners, our group has, since 1986, conducted a large cohort
      study involving six experienced NFP centers. Timing of conception was determined
      from NFP charts, in which women recorded days on which intercourse occurred. The
      number of days from the most probable conception intercourse to probable day of
      ovulation was first determined, and used as an estimate of the time gametes
      remained in the genital tract before fertilization. Several studies have already
      been completed, cohort as well as case-control in nature.

PMID- 9288339
TI  - Effects of timing of conception on birth weight and preterm delivery of natural
      family planning users.
AB  - OBJECTIVE: Various birth defects and untoward perinatal outcomes have been
      claimed to be associated with pregnancies conceived by gametes aged in vivo
      before fertilization. Thus, these outcomes were systematically assessed in
      pregnancies occurring in natural family planning (NFP) users. Our international
      multicenter cohort study of NFP pregnancies (n = 877) is by far the largest
      systematic study designed to assess pregnancy outcome and is of sufficient power
      to allow us to address the concern of low birth weight (< 2500 g) and preterm
      delivery (< 37 weeks gestation). STUDY DESIGN: In addition to gathering baseline
      medical data, evaluation was performed at 16 weeks, 32 weeks and at term. Data
      were collected in a systematic cohort fashion, verified by the five collaborating
      international recruiting centers, and analyzed by investigators in the US. Most
      recruiting center principal investigators are obstetrician-gynecologists and, if
      not, have integral relationships with such specialists. Standard criteria could
      thus be applied within and among centers. In our cohort, birth weight was
      recorded accurately at delivery. Almost all of the deliveries occurred in
      hospitals; thus, data should be quite reliable. Neonatal examination for
      anomalies was usually conducted immediately after delivery, when birth weight was
      recorded. RESULTS: Analysis of risk factors for low birth weight and preterm
      delivery showed that this population had a low risk profile. Low birth weight
      infants (< 2500 g) and preterm deliveries were increased among women with a
      history of either prior low birth weight or preeclampsia in the index pregnancy.
      However, mean birth weight was unaffected by the timing of conception vis a vis
      ovulation or pregnancy history. Mean birth weight for the 877 singleton NFP
      pregnancies was 3349.6 g. The risk of preterm delivery was increased among older
      women who drank alcohol, but there were no significant effects of timing of
      conception vis a vis ovulation on preterm delivery. Results held when analysis
      was stratified according to whether NFP was being used for contraception or to
      achieve pregnancy. CONCLUSIONS: Our data do not appear to show striking
      differences between 877 NFP pregnancies and the general obstetric population. The
      timing of conception vis a vis ovulation does not exert significant effects on
      the birth weight or preterm delivery of resulting pregnancies, a reassuring
      finding for NFP users.

PMID- 9288341
TI  - Requirements for NFP service delivery: an overview.
AB  - This paper reviews the salient features of natural family planning (NFP) and how
      it is provided. It also reviews the issues that influence how NFP is mainstreamed
      including client needs, provider expectations and capabilities, service delivery
      strategies and policy questions. Ways providers could make NFP easier for clients
      to learn include incorporating fertility awareness in all family planning client
      education efforts, teaching NFP in groups, and using a competency-based approach
      to teach NFP. The question of whether NFP teachers need to be users is analyzed
      from historical and current perspectives, and four options are presented for
      organizing NFP services in multi-method settings. Finally, the policy issues that
      multi-method providers will need to address when NFP is incorporated into their
      choice of methods are discussed.

PMID- 9288342
TI  - Main-streaming NFP into the Department of Health of the Philippines:
      opportunities and challenges.
AB  - In 1994, the Department of Health (DOH) of the Philippines issued a circular
      which reaffirmed natural family planning (NFP) as one of the basic services to be
      offered in all government family planning service sites and urged family planning
      workers to develop competence in teaching NFP methods. Although the circular
      represented a major policy breakthrough for the main-streaming of NFP it found
      the department without the capability or experience to directly provide NFP
      services. The two approaches the department is taking to respond to this new
      policy initiative are described in this paper. The selection of these approaches
      was influenced by the devolution of central government authority to local
      government units. The approaches include developing department capability in NFP
      training, service provision and service installation and creating a supportive
      program and policy environment. DOH partnership with an NFP non-government
      organization (NGO) has been critical in developing NFP capability within the
      government sector, particularly in NFP training and service installation.

PMID- 9288344
TI  - Factors to address when periodic abstinence is offered by multi-method family
      planning programs.
AB  - Multi-method family planning programs are committed to informed free choice of
      contraceptives. Thus they are expected to provide information and education, and
      facilitate access to services for those individuals and couples who want to
      practice periodic abstinence. Various factors affect the commitment and ability
      of multi-method family planning programs for providing periodic abstinence
      services. These factors include the effectiveness and cost of the method,
      attitude and technical competence of service providers, information and education
      strategies, and approaches for providing services. These factors are discussed in
      this paper. Information on providing periodic abstinence in a multi-method
      service situation is very scarce. The need for research, particularly operations
      research, for gathering information to guide program managers and service
      providers in the integration of periodic abstinence services is discussed.

PMID- 9288343
TI  - Comparing a public and private sector NFP program: implications for NFP
      expansion.
AB  - This paper synthesizes a six year collaboration between a natural family planning
      (NFP) non-governmental organization (NGO) and the National Health Service of the
      Emilia Romagna region in Italy. It also compares the public program experience
      with NFP services provided in the private sector in the adjacent region of
      Veneto. Midwives provided NFP services in government family health clinics while
      in the private sector NFP was taught by non-health laypersons in a church-based
      facility. The populations served by these two programs were different. Women in
      the public sector were slightly older and two-thirds were married. Forty percent
      of the clients had chosen to use NFP to achieve a pregnancy. The private sector
      client, recruited in part through premarriage counseling programs, was equally
      divided between married and single women, though the majority came for advice on
      avoiding or spacing pregnancies. In both regions NFP users were more highly
      educated than the general population.

PMID- 9288345
TI  - Approaches for incorporating ovulation detection devices and home kits into
      learning NFP--implications for service delivery.
AB  - This paper presents demographic data about use of NFP in Europe and the factors
      which have been identified as influencing that very low use level. Experience
      with a new ovulation detection device in clinical trials and observations of its
      over-the-counter promotions is discussed in the context of what is already known
      about how to maximize uptake of contraception in main-stream service provision.
      Some suggestions are offered as to appropriate means of encouraging women who are
      using artificial methods or no method to understand enough about their natural
      fertile cycle to consider NFP as an acceptable option.

PMID- 9288346
TI  - Expanding the availability and improving delivery of natural family planning
      services and fertility awareness education: providers' perspectives.
AB  - Despite the recognized benefits for clients and programs of providing natural
      family planning (NFP) services, few family planning programs offer NFP and few
      provide fertility awareness education. Furthermore, many non-governmental
      organizations (NGOs) that provide only NFP actually reach a very small percentage
      of the potential NFP users in the areas they serve. This paper discusses the
      results of interviews with selected family planning providers that were conducted
      to explore reasons why NFP and fertility awareness education are not offered in
      their programs, and with NFP providers to get their opinions on how to improve
      service delivery. The interviews were structured around some of the lessons
      learned from the successful incorporation of the lactational amenorrhea method
      (LAM) into several multimethod family planning programs. There is agreement that
      the need for NFP services* is far from being met and that most clients lack the
      information and skills they could learn through fertility awareness education.
      The providers interviewed also acknowledged that offering these services would
      improve the quality of reproductive health services in general. Presented here
      are some ideas about why these services are not offered, as well as suggestions
      for integrating NFP and fertility awareness education into existing family
      planning programs.

PMID- 9288347
TI  - The behavior of Italian family physicians regarding the health problems of women
      and, in particular, family planning (both contraception and NFP).
AB  - The hospital-centered trend that has dominated medical culture and the management
      of health care during this entire century has, in the last few years, undergone a
      reversal in Italy. Conditions in other countries suggest that similar changes
      have or will become increasingly common. The family physician today manages many
      of the functions previously handled by hospitals and specialists. In the field of
      reproductive health, family physicians are responsible not only for diagnosis and
      treatment, but also for prevention and education. The present study considers
      this new context with the objective of investigating the knowledge and behavior
      of Italian family physicians in the field of women's health, with particular
      regard to family planning (including natural family planning), through (1) a
      qualitative study (focus groups) of a small group of family physicians and (2) a
      questionnaire sent to 500 family physicians throughout Italy. The results of the
      focus group are summarized in the form of obstacles that the family physician
      finds in providing family planning services and proposals for change. The results
      indicate that because of their holistic approach, the family physician is an
      appropriate provider of family planning services although continued use of
      specialists' services, changes in logistics of the family physicians' practice,
      increased gender sensitivity, and additional training and information are
      necessary. The results of the questionnaire (121 responses, 24.2%) indicate that
      the Italian family physician currently lacks certain important information about
      family planning and would require logistical support to provide these services
      but is interested in acquiring information and is an appropriate family planning
      provider. An additional challenge for encouraging family practitioners to provide
      natural methods is that they favor a "medical" approach rather than a
      "behavioral" one in their treatment preferences for several other conditions.

PMID- 9288348
TI  - The benefits and barriers associated with a national natural family planning
      service: the New Zealand experience.
AB  - This paper provides a case study of a model for expanding natural family planning
      (NFP) from a small local program to the national level through the creation of a
      national association and the development of a public-private partnership. The
      experience of the New Zealand Association of Natural Family Planning (NZANFP) is
      analyzed in terms of both the benefits and barriers of using this model.
      Recommendations are given to guide others in developing a similar model.

PMID- 9288349
TI  - Gender, sexuality and communication issues that constitute barriers to the use of
      natural family planning and other fertility awareness-based methods.
AB  - Fertility awareness-based methods of family planning are rarely offered through
      reproductive health services in Latin America, despite evidence that many women
      use them. Providers state that clients do not want these methods, but provider
      bias is evident. Providers overestimate the difficulty of learning and using
      fertility awareness-based methods, and they underestimate their efficacy. Both
      providers and clients have difficulty dealing with sexuality (which is central to
      fertility awareness-based methods). Many providers lack gender sensitivity,
      'worsening' the unequal relationship between providers and clients. Experience
      has shown that when fertility awareness-based methods are well provided, they can
      have a positive effect on sexuality, self-understanding, and equality in the
      couple's relationship.

PMID- 9288350
TI  - Reproductive health awareness: an integrated approach to obtaining a high quality
      of health.
AB  - The Georgetown University Institute for Reproductive Health has evolved a multi
      dimensional approach to reproductive health education which has grown from their
      work in natural family planning and fertility awareness. This cohesive approach
      offers help to community, educational, and health organizations in providing
      knowledge and skills development in body/self-care, gender awareness, sexuality,
      and interpersonal communications.

PMID- 9288351
TI  - Body/self awareness and interpersonal communications: fundamental components of
      reproductive health awareness.
AB  - To protect and advocate for their own reproductive health, people of all ages can
      greatly benefit from enhanced body/self awareness and strong interpersonal
      communication skills. Body/self awareness and interpersonal communications, along
      with gender awareness and the integration of sexuality, are the fundamental
      components of a new approach to obtaining high quality health called reproductive
      health awareness.

PMID- 9288352
TI  - The potential contribution of sexuality and gender awareness.
AB  - To make well-informed decisions about reproductive health, individuals need
      information about their body, gender and sexuality as well as the communication
      skills to convey their choices to their family, partners and health care
      providers. Gender and sexuality are at the core of each individual's identity;
      understanding and acceptance of these aspects of ourselves is basic to our
      ability to have healthy relations with self, family and sexual partners.
      Throughout an individual's life cycle information is needed about gender and
      sexuality changes according to needs of their age group. A holistic approach to
      reproductive health is needed, based in the community where people live, in the
      schools where young people study and in the community health care centers where
      they receive services.

PMID- 9288354
TI  - The reproductive health awareness (RHA) model: a qualitative perspective.
AB  - The Reproductive Health Awareness model developed by Georgetown University
      Institute for Reproductive Health is responsive to the elements of quality of
      care articulated by Judith Bruce in 1989. The model encourages self-choice
      regarding family planning options, informed choice and flexibility to change
      family planning options with changing circumstances, and inclusion of men and the
      family. Providers utilizing the model must know the stages of behavior change and
      how to program care based on the client's knowledge and readiness, and how to
      communicate with clients such that they are facilitating care rather than
      prescribing it.

PMID- 9288353
TI  - Reproductive health awareness: an important dimension to be integrated into
      existing sexual and reproductive health programs.
AB  - The ultimate goal of any sexual and reproductive health program is to ensure cost
      effectiveness, quality and sustainability. Reproductive health awareness is an
      educational approach which is both relevant and sensitive to many communities'
      existing sexual and reproductive health needs and concerns. When working with
      community groups, a participatory approach that includes reproductive health
      awareness concepts is a simple non-threatening way for programs to quickly expand
      beyond pure information giving and explore what reproductive health means to
      people. Although many community sexual and reproductive health programs do not
      the term reproductive health awareness, they use techniques similar to the
      reproductive health awareness education approach, when facilitating discussions
      about sexual or reproductive health. If reproductive health awareness is
      identified and included as one of the dimensions of future sexual and
      reproductive health programs, this will hopefully strengthen the program's
      overall quality and effectiveness.

PMID- 9288356
TI  - Changing behavior: a challenge for reproductive health awareness.
AB  - Social marketing applies commercial sector ideas to programs to change behavior.
      It involves a mindset that is customer-focused; a process that starts with
      customers and continually returns to them for validation; and concepts to make
      change happen. Customer behavior models guide strategy. One useful model is based
      on stages of change and four behavioral influences: perceived benefits, perceived
      costs, the influence of others, and perceived behavioral control.

PMID- 9288355
TI  - Issues to consider in operationalizing reproductive health.
AB  - The International Conference on Population and Development (ICPD) served as the
      international launchpoint for a broadened reproductive health agenda, bringing
      global attention to a variety of underlying issues that impact on women's health
      and well-being, and highlighting the need to redress imbalances in gender equity
      that have had negative health and social consequences in particular for women and
      girls. To meet the challenges of the ICPD, programs must assess, prioritize and
      implement an expanded set of reproductive health interventions within an
      environment of diminishing resources. This paper argues that hidden social and
      health costs that particularly affect women must be included in the assessment
      and prioritization of reproductive health interventions. In addition, it argues
      that issues of gender and sexuality cannot be separated from the delivery of
      appropriate family planning and reproductive health care if we are to have a
      significant impact on improving the reproductive health of current and future
      generations.

PMID- 9288358
TI  - Implementing reproductive health awareness: progress to date.
AB  - This paper describes the experience of various institutions in integrating a
      reproductive health awareness (RHA) approach into different health, school and
      community-based programs. RHA, an educational approach that evolved from the
      Institute's client empowerment approach to natural family planning and fertility
      awareness, is based on helping women and men to participate actively in their own
      family planning and reproductive health care by developing skills in self
      observation, communication and self-advocacy. In addition to providing the
      Institute with an avenue for responding to the Cairo and Beijing mandates, RHA
      has also provided a means to introduce family planning, particularly natural
      methods of family planning, into programs and institutions. RHA has continued to
      evolve and strengthen during the process of field testing its contributions to
      existing reproductive health programs.

PMID- 9288357
TI  - Breaking the mold: expanding options for reproductive health awareness: the CARE
      experience.
AB  - The early years of the CARE family planning and reproductive health program were
      geared primarily toward modern methods of contraception and providing services.
      However, new and fresh opportunities to address reproductive health awareness and
      natural family planning are now emerging as important options. In these programs,
      coordination and collaboration with other sectors such as food and nutrition,
      children's health and natural resource management, combined with more
      sophisticated approaches for assessing need and reaching communities with
      information, has resulted in more people being reached than ever before with
      appropriate options and opportunities for reproductive health awareness and care.
      There are examples of CARE projects from India, Peru and Nepal where activities
      which feature working across development sectors and engaging communities to
      address their individual and collective RH needs are featured. Ways to
      disseminate information about reproductive health are being broadened to include
      creative combinations of interpersonal, mass and folk media', whether it be an
      informal one-to-one counseling session with flipcharts, a community mobilization
      event, a multi-media campaign, or any combination thereof. Likewise, the target
      audience need not always be the women of reproductive age, not should the RH
      messengers always be the medical and public health professionals. What is
      critical in all of these instances is to craft strategies based on appropriate
      research and need, continuously monitor progress, refine approaches as necessary,
      track results and evaluate the process and impact of interventions leading to
      behavior change. The challenge is not insignificant, but the rewards to be reaped
      through the improved programs are clearly worth striving for.

PMID- 9288359
TI  - Experimental evidence of a plant meridian system: IV. The effects of acupuncture
      on growth and metabolism of Phaseolus vulgaris L. beans.
AB  - We have shown previously that plants exhibit functional characteristics similar
      to the meridian system in humans and animals, such as high potential and low
      electrical resistance, high temperature, and spontaneous sound production. Here
      we will show the effect of acupuncture on plants. When plants of Phaseolus
      vulgaris L. pole bean (cv. Kentucky wonder) and bush bean (cv. Slenderette) were
      subjected to acupuncture by inserting two needles into opposite sides of the stem
      of the unifoliolate buds, it was found that acupuncture strengthened the growth
      and development of the plants. Two repeated experiments showed that the mean net
      photosynthesis rate of plants subjected to acupuncture increased about 20.5%, the
      mean transpiration 27.2%, the growth and total length of internodes 22.5%, and
      the total dry weight of shoots from the cotyledon to the apex 22.9%, in
      comparisons with control plants under the same growing conditions. In addition,
      treated plants flowered three days earlier and had 14.4% more fruit than the
      untreated control plants. Thus, acupuncture may serve as a viable technique for
      increasing yield in agricultural plants.

PMID- 9288360
TI  - Effect of indirect moxibustion on mouse skin.
AB  - Effect of indirect moxibustion stimulation on mouse skin was studied by thermal
      qualitative, biochemical, and histological methods. The maximum temperature
      change by indirect moxibustion was about 65 degrees C on the skin, and 45 degrees
      C in the subcutaneous layer. The treatment of indirect moxibustion was found to
      be associated with the decrease of lipid peroxidation and increase of superoxide
      dismutase (SOD) in the skin. Histological findings after indirect moxibustion
      showed an increase in the number of hair mother cells and hypertropy of the
      cells.

PMID- 9288361
TI  - Evaluation of the antioxidant and hepatoprotective activity of Terminalia
      catappa.
AB  - The free radical scavenging and antihepatotoxic activity from Terminalia catappa
      was studied. Treatment with T. catappa water extracts showed antihepatotoxic
      activity against CCl4-induced toxicity in the rat liver that was tested. The
      crude drug also exhibited anti-oxidant effects in FeCl2-Ascorbic acid induced
      lipid peroxidation in the rat liver homogenate. Moreover, the superoxide radical
      scavenger effect of T. catappa was demonstrated using electron spin resonance
      (ESR) and spintrapping technique. The results indicate that T. catappa possesses
      good antihepatotoxic activity and superoxide radical scavenger activity.

PMID- 9288362
TI  - Effects of siegesbeckia pubescens on immediate hypersensitivity reaction.
AB  - This study was carried out to examine the effect of an aqueous extract from
      Siegesbeckia pubescens (Compositae) (SPAE) on immunoglobulin E (IgE)-mediated
      immediate hypersensitivity reaction. Forty-eight hours passive cutaneous
      anaphylaxis in rats was significantly inhibited by oral administration of SPAE
      (100 micrograms/g). It also inhibited histamine release from rat peritoneal mast
      cells induced by anti-dinitrophenyl (DNP)-IgE and DNP-human serum albumin. The
      data indicate that SPAE has antiallergic activity, and that its action may be due
      to inhibition of histamine release from mast cells.

PMID- 9288363
TI  - Hypoglycemic action of embelia madagascariensis in normal and diabetic mice.
AB  - The hypoglycemic effect of Embelia madagascariensis (Myrsinaceae) was
      investigated in both normal and streptozotocin-induced diabetic mice. The
      methanol extract of leaves of Embelia madagascariensis (EL)(500 mg/kg) reduced
      the blood glucose of normal mice from 206 +/- 9 to 137 +/- 10 mg/100 ml 4 hours
      after intraperitoneal administration (P < 0.001), and also significantly lowered
      the blood glucose of streptozotocin-induced diabetic mice from 570 +/- 29 to 401
      +/- 59 mg/100 ml under similar conditions (P < 0.05). EL also suppressed
      epinephrine-induced hyperglycemia in mice (control vs EL, P < 0.01).

PMID- 9288364
TI  - Studies on the antimicrobial activity of juglans regia.
AB  - Juglans regia L. bark is used in some countries as a toothbrush and as a dye for
      coloring the lips for cosmetic purposes. Its extract showed a broad spectrum
      antimicrobial activity in a dose dependent manner. It inhibited the growth of
      several species of pathogenic micro-organisms representing Gram-positive bacteria
      (Staphylococcus aureus and Streptococcus mutans), Gram-negative bacteria
      (Esherichia coli and Pseudomonas aeruginosa) and a pathogenic yeast (Candida
      albicans). The extract has either synergistic or additive action when tested with
      a wide range of antibacterial drugs. It also increased the pH of saliva. Thus,
      brushing the teeth with this bark may improve oral hygiene, prevent plaque and
      caries formation, and reduce the incidence of gingival and periodontal
      infections.

PMID- 9288365
TI  - Antifungal activity of plant extracts against Candida albicans.
AB  - In previous papers, we reported the antimicrobial activity of plants used in
      Argentine folk medicine against different micro-organisms. The present study
      deals with the screening of 11 of these plants against the opportunistic pathogen
      fungus Candida albicans. Aqueous extracts 6% p/v (6 mg dry plant per 100 ml of
      water) were checked against fungus cultures by the agar-well diffusion method.
      Five extracts showed antifungal activity.

PMID- 9288366
TI  - Ameliorative effect of traditional Chinese medicine prescriptions on alpha
      naphthylisothiocyanate and carbon-tetrachloride induced toxicity in rats.
AB  - Syh-Mo-Yin (SMY), Guizhi-Fuling-Wan (GFW), Shieh-Qing-Wan (SQW) and Syh-Nih-San
      (SNS) are prescriptions of Traditional Chinese Medicine (TCM) for liver disease.
      The effects of these four prescriptions against experimental liver injury induced
      by alpha-Naphthylisothiocyanate (ANIT) and carbon tetrachloride (CCl4) were
      studied. Rats treated with ANIT (100 mg/kg) exhibited elevations of serum total
      bilirubin (TBI), alkaline phosphatase (ALP), glutamate-oxalatetransaminase (sGOT)
      and glutamate-pyruvate-transminase (sGPT) as well as cholestasis and
      parenchymanecrosis. In rats receiving SMY, SQW and SNS treatment after ANIT
      challenged, the biochemical and morphological parameters of liver injury were
      significantly reduce. Elevated lipid peroxidation (LPO) level in liver tissue,
      associated with an increase in serum GOT and GPT level, was observed in CCl4
      treated rats. Treatment with these four prescriptions on CCl4-induced liver
      injury rats showed a remarkable hepatoprotective effect. A significant decrease
      in peroxidative level suggested that these prescriptions have anti free radical
      properties.

PMID- 9288368
TI  - Analgesic effect of a herbal medicine for treatment of primary dysmenorrhea--a
      double-blind study.
AB  - We evaluated the analgesic effect of Toki-shakuyaku-san (TSS) in women who had a
      combination of "deficiency," of "Yin," "cold," and "stagnated blood" syndromes,
      and were suffering from dysmenorrhea. A diagnostic scoring system was used for
      determination of these conditions. We treated patients with either TSS or placebo
      during 2 menstrual cycles with a double-blind technique, and we followed them for
      2 additional cycles. A significant alleviation of dysmenorrhea was observed in
      patients treated with TSS as compared to those treated with placebo. Our results
      suggest that TSS is effective for treatment of dysmenorrhea in patients with the
      above-mentioned conditions.

PMID- 9288367
TI  - The effects of ninjinyoeito on cultured venous endothelial cells.
AB  - The effects of Ninjinyoeito on endothelial cells in human umbilical veins was
      examined. We found that Ninjinyoeito accelerates the inhibition and decomposition
      of Endothelin-1 production, which is known to constrict veins and raise blood
      pressure, and promote the synthesis of nitric oxicide which is known to have a
      vasophypotonic effect. We also found that Ninjinyoeito accelerates Interleukin 1
      beta (IL-1 beta) production. IL-1 beta is a substance that plays important roles
      in maintaining the homeostasis of living organisms in immunity and inflammation,
      for example, as well as in the production of tissue plasminogen activators, which
      are known to have an anti-thrombotic effect on blood coagulation and on the
      fibrinolysis mechanism. Thus, it is suggested that Ninjinyoeito is effective in
      accelerating the physiological functions of human vein endothelial cells in
      vitro.

PMID- 9288369
TI  - Computerized color analysis of "xue yu" (blood stasis) in the sublingual vein
      using a new technology.
AB  - Computer-assisted image analyses were performed on the color of the tongues of 95
      medical students to enhance the accuracy and objectivity of tongue inspections
      for determining blood stasis. Areas from the sublingual vein were selected and
      subjected to image analysis. A slide scanner was used to digitize the color
      slides, and the digital information was transmitted to a personal computer for
      subsequent feature extraction and analysis. A comparison was then made between
      the computerized data using Red-Green-Blue color components, and inspection with
      the naked eye based on the diagnostics of traditional Chinese medicine. The
      results obtained suggest that there are statistically significant correlations
      between visual analyses and the computerized normalized R value (F value; 3.397,
      p < 0.05). The examination of sublingual veins with the naked eye showed the
      validity of computer-assisted image analysis. This analysis may provide a
      potential solution to the demand for a sophisticated means of quantitative and
      qualitative observation of physiological parameters regarding blood stasis,
      including that for the sublingual vein.

PMID- 9288370
TI  - Comparison between ethnopharmacology in traditional Chinese medicine and
      Brazilian popular phytotherapy.
AB  - 850 Chinese medicinal plants contained in various publications were compared with
      plants existing in Brazil. The species were classified according to Chinese
      ethnopharmacological groups, and these were compared to Brazilian ones. According
      to the principles proposed by the author, 122 species existing in Brazil could be
      related to the Chinese species (14.35% of the samples). In this comparison,
      62.27% of the plants had similar ethnopharmacological use. Comparison between the
      ethnopharmacological groups showed some similarity in 91.60%. Pharmacological
      actions disclosed by research also showed concordance with ethnopharmacological
      uses.

PMID- 9288371
TI  - Service quality of Chinese traditional medicine in Taiwan: a comparative study.
AB  - A consensus is growing that measuring service quality level based on patients'
      perceptions is crucial for continuous improvement. This work involved a
      questionnaire survey to evaluate the gap of perceived service quality level
      between Chinese traditional medicine and Western medicine in Taiwan. The ten
      dimensions of service quality proposed by Parasuraman et al. (1985) were adopted
      as a framework to design an instrument. The results of data analyses indicated
      that significant differences arise in perceived quality level between the two
      systems in four dimensions: competency, tangibles, courtesy, and communication.
      Managerial implications of the results were discussed. We recommend that the two
      systems learn from each other to enhance patient satisfaction.

PMID- 9288372
TI  - Clearing the airway--mouth gags, wedges and openers.

PMID- 9288373
TI  - Effect of low concentrations of prostacyclin on platelet function in vitro.
AB  - The study was performed to determine the possible direct effects of low
      concentrations of prostacyclin that might spill over into the systemic
      circulation during the administration of inhaled aerosolized prostacyclin.
      Platelet aggregation in response to adenosine diphosphate and collagen, as well
      as measurement of the maximum amplitude of the thrombelastograph (TEG), was
      undertaken in vitro using venous blood exposed to low concentrations of
      prostacyclin (0, 10, 100 and 500 pg/ml) from eight healthy volunteers. There were
      statistically significant reductions in parameters of platelet aggregation in
      response to the agonists adenosine diphosphate (1 mumol/l and 8 mumol/l) and
      collagen (10 mumol/l) following exposure to as little as 10 pg/ml of
      prostacyclin. The maximum amplitude of the TEG was unchanged over the entire
      range of prostacyclin concentrations studied. The results indicate that low
      concentrations of prostacyclin or prostacyclin metabolite such as may be observed
      during inhaled aerosolized prostacyclin therapy are likely to be associated with
      a marked platelet aggregation defect. This defect was not detected by the TEG.

PMID- 9288374
TI  - The effect of supplemental oxygen on the incidence of hypoxaemia after
      premedication in patients undergoing cardiac surgery.
AB  - Opiate premedication may cause significant respiratory depression, particularly
      when other sedative agents such as scopolamine or benzodiazepines are added. This
      can cause hypoxaemia with potential for worsening myocardial ischaemia in cardiac
      surgery patients. The aim of this study was to investigate the incidence of
      hypoxaemia (SpO2 < 90%) in elective patients undergoing cardiac surgery and to
      assess the efficacy of supplemental oxygen in preventing it. One hundred elective
      patients without significant respiratory disease or cardiac failure, who received
      both an opiate and a sedative premedication, were prospectively randomized to
      receive either oxygen via a facemask at 4 l/min or no oxygen. Continuous arterial
      oxygen saturation was recorded using a pulse oximeter from the time of
      premedication until the patient arrived in theatre. An SpO2 < 90% was recorded as
      a significant event and oxygen was administered to the patients. Six patients
      were excluded because of equipment failure or protocol violations. The patient
      groups were comparable with respect to patient demographics, premedication type
      and dose or the duration of monitoring. In patients receiving oxygen (n = 48)
      there were no episodes of hypoxaemia (0%). In patients not receiving oxygen (n =
      46) there were 14 episodes of hypoxaemia (30%, P < 0.0001). We conclude that
      there is a significantly high incidence of hypoxaemia in cardiac surgery patients
      following combined opiate and sedative premedication and that it can be reduced
      by the routine administration of supplemental oxygen.

PMID- 9288375
TI  - Polyurethane central venous catheters, hydrochloric acid and 70% ethanol: a
      safety evaluation.
AB  - Three groups of polyurethane central venous catheters (CVC) were infused daily
      for twenty days with 0.1 normal hydrochloric acid, 70% ethanol and normal saline
      (control) respectively to look for any changes in microscopic structural
      integrity. A 1 cm segment was cut from the distal end of each CVC daily. All
      sections were examined in a scanning electron microscope, looking for evidence
      either of damage to the lumen surface or of wall thinning. No significant damage
      to the lumen surfaces was observed with either treatment. Sporadic fine surface
      pitting appeared late in the study without any clear temporal or treatment
      related pattern. The mean CVC wall thickness did not change significantly over
      the study period (P = 0.15). Qualitative softening of ethanol treated catheters
      was observed, and this finding limits the recommendations for the use of ethanol.
      0.1N HCl does not compromise the structural safety of the catheters, and its use
      should be considered when polyurethane CVC. become occluded.

PMID- 9288376
TI  - Bacteraemia following percutaneous dilational tracheostomy.
AB  - This study reports the incidence of bacteraemia following 106 consecutive bedside
      percutaneous tracheostomies. Post-tracheostomy blood culture results were
      compared with other blood cultures from the same population. The incidence of
      positive post-tracheostomy blood cultures was 10.4% (11/106), compared with 6.6%
      (7/106) for other blood cultures (odds ratio 1.64, 95% confidence interval 0.61
      4.40, P = 0.46). Staphylococcus epidermidis was the most common organism
      cultured, 7/106 (6.6%) of post-tracheostomy cultures, compared with 3/106 (2.8%)
      for other cultures (odds ratio 2.43, 95% confidence interval 0.61-9.65, P =
      0.33). The other four post-tracheostomy cultures grew an organism cultured from
      that patient's tracheal secretions. Seventy-four patients were receiving
      antibiotics at the time of tracheostomy, of these 7 (9.5%)-had positive blood
      cultures, a similar incidence (4 of 32, 12.5%) to those not receiving antibiotics
      (odds ratio 0.73, 95% confidence interval 0.20-2.70, P = 0.90). We conclude
      bacteraemia is a common complication of percutaneous tracheostomy; the causative
      organisms come from the patients' trachea or skin.

PMID- 9288377
TI  - Midazolam-flumazenil topical anaesthesia for microlaryngoscopy with jet
      ventilation.
AB  - A comparison between midazolam and midazolam-flumazenil for total intravenous
      anaesthesia in combination with topical anaesthesia and muscle relaxants was
      performed in a double-blind, parallel study in 40 patients scheduled for
      microlaryngoscopy with or without bronchoscopic procedures using jet ventilation
      with oxygen. A single intravenous injection of midazolam 0.3 mg/kg, lignocaine
      spray and muscle relaxants provided adequate anaesthesia and good operative
      conditions throughout the procedures, which took 20 to 30 minutes. Patients who
      had placebo at the end of the procedures had a longer recovery and a high
      incidence of airway obstruction (20%). Administration of flumazenil provided
      prompt awakening in 19 of 20 patients (95%) within five minutes, resulting in
      rapid and favourable recovery without resedation or other side-effects, while
      only three of 20 (15%) patients in the placebo-treated group had improved
      consciousness within five minutes. The simplicity and reliability of the
      midazolam-flumazenil technique is attractive. We consider it worthy of further
      investigation for wider application in clinical practice.

PMID- 9288378
TI  - Tracheostomy in a neuro-intensive care setting: indications and timing.
AB  - A retrospective review was made of 49 survivors who were mechanically ventilated
      for more than 48 hours in the neurosurgical ICU. Thirty-two patients (Gp I) were
      successfully extubated, 9 patients (Gp II) underwent tracheostomy after one or
      more failed extubations, and 8 patients (Gp III) underwent elective tracheostomy.
      Glasgow Coma Scale (GCS) scores at extubation were 11.3 +/- 2.8 (mean (SD) for Gp
      I vs 7.8 +/- 2.7 for Gp II (P = n.s.) and at elective tracheostomy (Gp III) was
      5.4 +/- 2.3. Incidence of ventilator-associated pneumonia were 35% in Gp I vs
      100% of patients in Gp II and III (P < 0.05). Reasons for reintubation in 7 of 9
      patients (Gp II) were upper airway obstruction and tenacious tracheal secretions
      while 14 of 17 patients were weaned off the ventilator within 48 hours of
      tracheostomy. The length of stay in ICU was 16.8 +/- 7.1 days in Gp II vs 11.7 +/
      2.9 days in Gp III (P < 0.05). In our study, elective tracheostomy for selected
      patients with poor GCS scores and nosocomial pneumonia has resulted in shortened
      ICU length of stay and rapid weaning from ventilatory support.

PMID- 9288379
TI  - Plasma lignocaine concentration following nebulization for awake intubation.
AB  - Nebulization of lignocaine is a common technique for preparing the airway prior
      to awake intubation. The aim of the study was to assay the serum levels of
      lignocaine. Ten ASA I volunteers had 6 mg/kg of 10% lignocaine solution nebulized
      via facemask. Blood assays for peak levels were performed. Mean peak serum
      lignocaine level was 0.29 mg/l with a highest measurement of 0.45 mg/l. This peak
      occurred 30 minutes following commencing nebulization. No subject developed
      symptoms or signs of lignocaine toxicity. Peak plasma lignocaine levels were an
      order of magnitude below the accepted toxic threshold of 5 mg/l. This indicates
      that supplemental doses of lignocaine via the bronchoscope can be given with
      safety.

PMID- 9288380
TI  - Charging for intensive care using direct nursing hours as the cost marker.
AB  - The hypothesis that direct nursing hours correlate with the cost of a patient
      stay in intensive care was tested. One hundred and thirty-nine patients were
      studied and the data collected included: (a) direct nursing hours applied to each
      patient; (b) a daily TISS score: (c) a detailed costing of each patient (all
      costs are shown in N.Z.$). There was a strong correlation between the direct
      nursing hours and the total cost per patient (r2 = 0.98) (total cost = 54 x
      direct nursing hours + 344). Also a strong correlation existed between the total
      TISS scores and the total costs per patient (r2 = 0.96) (total cost = 67.13 x
      TISS). Direct nursing hours offer a relatively simple and logical method of
      allocating costs per patient.

PMID- 9288381
TI  - Retrospective review of 100 cases of endoluminal aortic stent-graft surgery from
      an anaesthetic perspective.
AB  - One hundred cases of endoluminal aortic stent surgery were retrospectively
      reviewed and analysed with respect to outcome. The overall mortality rate was
      consistent with standard rates for open surgical repair. One hundred per cent of
      patients who developed multiorgan failure died (7), as did 78% of those who
      developed acute renal failure (9), and 55% of those who had a serum creatinine
      rise greater than 100 mumol/l (9). Patients given mannitol had an increased
      incidence of a serum creatinine rise of greater than 100 mumol/l, at 16% versus
      4% for those not given mannitol. Patients with documented intra- or postoperative
      anaemia (Hb < or = 80 g/l) had a mortality rate of 22% compared to 5% for non
      anaemic patients. The mortality rate increased from 3% to 15% if the procedure
      took more than four hours. The anaesthetic requirements for this new type of
      surgery are outlined and discussed with respect to these results. The surgical
      technique is summarized.

PMID- 9288382
TI  - The role of the anaesthetist during the transjugular intrahepatic porto-systemic
      stent shunt procedure (TIPPS).
AB  - A retrospective review of the clinical experience associated with the
      transjugular intrahepatic porto-systemic stent shunt procedure revealed that
      there was a potential for life-threatening critical incidents to occur. Adequate
      stabilization and facilities for advanced monitoring and resuscitation by skilled
      personnel are essential.

PMID- 9288383
TI  - Continuous extrapleural intercostal nerve block for post thoracotomy analgesia in
      children.
AB  - The safety and efficacy of continuous extrapleural intercostal nerve block has
      been well established in adults. This review of our initial paediatric experience
      suggests a role for this technique in children and discusses risks and benefits
      relative to other forms of regional analgesia for thoracotomy. Nine children aged
      one to twelve years received extrapleural infusions of bupivacaine 0.1-0.2%
      following lateral thoracotomy for lung resection. An extrapleural catheter was
      placed by the surgeon prior to thoracotomy closure, and correctly positioned
      under direct vision external to the parietal pleura alongside the vertebral
      column. An intraoperative loading dose of bupivacaine, 0.25-0.5% (0.28 +/- 0.1
      ml/kg, mean +/- SD) was injected so as to raise a bleb under the parietal pleura
      which spread longitudinally to bathe several intercostal nerves in the
      paravertebral gutter. The chest wall was then closed. Infusions of bupivacaine
      were commenced in the recovery room and continued at a constant rate of 0.21 +/-
      0.09 ml/kg/h for 72 +/- 15 hours. The mean dose of bupivacaine was 284 +/- 97
      micrograms/kg/h. Patients also received standard analgesia as an intravenous
      morphine infusion (10-50 micrograms/kg/h), or patient-controlled analgesia.
      Nursing staff were specifically instructed not to alter their usual management of
      variable rate morphine infusions which are titrated to adequate analgesia.
      Morphine requirements in the first 48 postoperative hours remained less than 30
      micrograms/kg/h, oral fluids were well tolerated after 31.2 +/- 19.1 hours,
      nasogastric tubes were removed at 16.7 +/- 11.2 hours. Postoperative nausea and
      vomiting and respiratory depression were not observed in any patient and all were
      able to comply with physiotherapy. There were no complications of catheter
      placement or bupivacaine administration. Our initial experience suggests that
      this is a safe technique which minimizes complementary opioid administration and
      provides adequate analgesia for children postthoracotomy for lung resection.

PMID- 9288384
TI  - Management of malignant hyperthermia susceptible parturients.
AB  - The management of eleven women susceptible to malignant hyperthermia during
      twenty deliveries is presented. These women were managed over a six-year period
      following guidelines that were established in 1990. Initial problems identified
      were the management of labour and caesarean section, the use of sympathomimetics
      and potential problems for the newborn, viz placental transfer of drugs and the
      possibility of a stress-induced malignant hyperthermia reaction in the newborn.
      There was little evidence that the stress of labour produced hypermetabolic
      responses in either mother or neonates and the use of sympathomimetics increased
      throughout the six-year period with no evidence of adverse effects. A caesarean
      section using general anaesthesia was not required but the management of this
      situation is described in both the protocol and discussion sections of this
      paper.

PMID- 9288385
TI  - Preliminary clinical use of a patient-controlled intranasal analgesia (PCINA)
      device.

PMID- 9288386
TI  - Laryngeal mask insertion following inhalational induction in children: a
      comparison between halothane and sevoflurane.
AB  - The aim of this study was to compare laryngeal mask insertion conditions
      following inhalational induction with either halothane or sevoflurane. Fifty
      eight healthy children scheduled for dental extraction were randomly assigned to
      receive nitrous oxide 66% in oxygen and 3.0 MAC of either halothane or
      sevoflurane introduced in a stepwise fashion. The laryngeal masks were inserted
      when an adequate depth of anaesthesia was attained and the reactions and time to
      insertion noted. Inhalational induction was smooth in both halothane and
      sevoflurane groups. Induction time and time to laryngeal mask insertion were
      significantly faster with sevoflurane. The conditions for laryngeal mask
      insertion were generally good with 86.2% and 89.2% in the halothane and
      sevoflurane groups respectively having had no reactions to insertion. The
      complications to laryngeal mask insertion encountered were mild. The emergence
      time from the anaesthetic was found to be shorter for sevoflurane but the
      difference was not statistically significant.

PMID- 9288387
TI  - Inspired oxygen concentrations with or without an oxygen economizer during ether
      draw-over anaesthesia.
AB  - An oxygen economizer tube is attached to draw-over vaporizers and acts as a
      reservoir of supplemental oxygen. The clinical importance of the presence or
      absence of the economizer tube (volume 130 ml) has not been adequately studied in
      manually ventilated patients using ether from an Ohmeda Cyprane Portable
      Anesthesia Complete (PAC) draw-over vaporizer. A total of sixteen patients ASA 1
      2, undergoing elective surgery for peripheral orthopaedic procedures were studied
      with and without an economizer tube. Each patient acted as his or her own
      control. Standard procedures were used for anaesthetic induction with muscle
      relaxant, endotracheal intubation and anaesthetic maintenance. Supplemental
      oxygen was supplied by an oxygen concentrator. Using the draw-over vaporizer
      without an oxygen economizer tube, there was a slight increase in FiO2 of 20%,
      23%, 27%, 30%, 33% and 33%, with increasing oxygen supplementation of 0 to 5
      l/min, respectively. With an economizer tube, the FiO2 values increased to 20%,
      26%, 35%, 46%, 54% and 66% at 0 to 5 l/min of oxygen respectively. The FiO2
      values were significantly different at 3, 4, and 5 l/min (P < 0.05), showing the
      potential advantages of an oxygen economizer tube attached to a draw-over
      vaporizer in this setting. No significant differences were seen in the oxygen
      saturations of these healthy patients with or without an oxygen economizer.

PMID- 9288389
TI  - Neck haematoma and airway obstruction in a pre-eclamptic patient: a complication
      of internal jugular vein cannulation.

PMID- 9288388
TI  - Massive air embolism with pulmonary arterio-bronchial fistula and ventricular
      septal defect.

PMID- 9288391
TI  - Propofol infusion for conscious sedation in dentistry in patients with
      involuntary movement disorders--a note of caution.

PMID- 9288390
TI  - Management of a low tracheal tear.

PMID- 9288392
TI  - Inadvertent intra-arterial midazolam.

PMID- 9288394
TI  - Recurrence of post dural puncture headache.

PMID- 9288393
TI  - Acute renal failure potentiated by gentamicin and calcium.

PMID- 9288395
TI  - Monitoring in anaesthesia and alarm systems.

PMID- 9288396
TI  - Bite blocks and the LMA.

PMID- 9288397
TI  - Uterine rupture and scar dehiscence.

PMID- 9288398
TI  - Injection port failure with blockage of intravenous tubing.

PMID- 9288399
TI  - Postoperative epidural ropivacaine.

PMID- 9288400
TI  - Pain associated with 2% lignocaine epidural anaesthesia.

PMID- 9288401
TI  - A non-radioactive and two radioactive assays for selenophosphate synthetase
      activity.
AB  - Selenophosphate synthetase catalyzes the formation of monoselenophosphate
      (SePO3(3-)) from ATP and selenide (reaction 1). [formula: see text] In one assay
      frequently used, [8-14C]AMP formation from [8-14C]ATP is estimated after
      separation of the nucleotides by thinlayer chromatography. An alternative non
      radioactive assay in which the AMP product is estimated using AMP deaminase is
      described. The highly oxygen-labile selenophosphate product can be estimated in
      an assay employing [gamma-32P]ATP. The 32P-labeled selenophosphate is converted
      to [32P]orthophosphate by treatment with iodine and estimated after removal of
      residual [32P]ATP on charcoal.

PMID- 9288402
TI  - cDNA and deduced polypeptide sequence of a mouse selenoprotein P.
AB  - An 11-day embryonic Swiss Webster/NIH mouse cDNA library was screened with a
      partial murine selenoprotein P cDNA probe and a murine selenoprotein-P-type cDNA
      clone of 2075 bp length was obtained. The clone contained a 5'-leader sequence of
      132 bp length, the selenoprotein P coding frame, and 803 base pairs in the 3'
      untranslated region. Alignment and RNA folding studies revealed the presence of
      two well conserved selenocysteine inserting motifs in the 3' flanking region. The
      deduced polypeptide sequence comprises 380 residues including ten
      selenocysteines. Identical amino acid residues in homologous positions are 86%,
      71%, and 64% when compared to the previously reported selenoprotein P sequences
      of rat, man, and cattle, respectively. The comparatively low similarity between
      the selenoprotein P sequences reported so far leaves open the question whether
      they belong to the same molecular clade.

PMID- 9288403
TI  - Lipoic acid increases de novo synthesis of cellular glutathione by improving
      cystine utilization.
AB  - Lipoic acid (thiotic acid) is being used as a dietary supplement, and as a
      therapeutic agent, and is reported to have beneficial effects in disorders
      associated with oxidative stress, but its mechanism of action remains unclear. We
      present evidence that lipoic acid induces a substantial increase in cellular
      reduced glutathione in cultured human Jurkat T cells human erythrocytes, C6 glial
      cells, NB41A3 neuroblastoma cells, and peripheral blood lymphocytes. The effect
      depends on metabolic reduction of lipoic acid to dihydrolipoic acid.
      Dihydrolipoic acid is released into the culture medium where it reduces cystine.
      Cysteine thus formed is readily taken up by the neutral amino acid transport
      system and utilized for glutathione synthesis. By this mechanism lipoic acid
      enables cystine to bypass the xc- transport system, which is weakly expressed in
      lymphocytes and inhibited by glutamate. Thereby lipoic acid enables the key
      enzyme of glutathione synthesis, gamma-glutamylcysteine synthetase, which is
      regulated by uptake-limited cysteine supply, to work at optimum conditions. Flow
      cytometric analysis of freshly prepared human peripheral blood lymphocytes, using
      monobromobimane labeling of cellular thiols, reveals that lipoic acid acts mainly
      to normalize a subpopulation of cells severely compromised in thiol status rather
      than to increase thiol content beyond physiological levels. Hence lipoic acid may
      have clinical relevance in restoration of severely glutathione deficient cells.

PMID- 9288404
TI  - The effects of insulin, transferrin and androgens on rat prostate explants in
      serum-free organ culture.
AB  - A model previously developed in our laboratory to culture rat prostate explants
      in serum-free chemically-defined medium was used to evaluate the direct influence
      of potential regulators. The aim of the present work was to verify the effects of
      insulin (I) and transferrin (Tr), two hormones considered as essential in other
      serum-free culture systems, and three androgenic hormones, since the prostate is
      known to be androgen-dependent. Explants of rat prostate were cultured for five
      days in serum-free Leibovitz's L-15 medium (37 degrees C, 95% air-5% CO2). The
      addition of Tr (50 micrograms/ml) had no effect, but I (5 micrograms/ml)
      significantly increased DNA synthesis. This influence was amplified by
      combination of the two hormones. However, protein synthesis was only slightly
      stimulated. Testosterone (T) or androstanediol significantly increased DNA
      synthesis when compared to corresponding control values at five days. In
      combination with I plus Tr, each hormone showed potentiated effects, particularly
      T with a twofold increase over day 0 values. When dihydrotestosterone was added
      singly, the incorporation of 3H-thymidine was stimulated by 300% over control
      values at five days, and by 100% over values in uncultured explants. This
      influence was maximal since it was not improved by I plus Tr. Protein synthesis
      was increased significantly by the triple combination. In addition, each androgen
      as well as the combination of I plus Tr had a positive influence on explant
      morphology. The above conditions optimize the present culture system and
      establish its usefulness as a valuable tool to study the direct influence of
      different effectors in prostate metabolism and to eventually identify putative
      cancer markers.

PMID- 9288405
TI  - Evidence for a functional relevance of the selenocysteine residue in mammalian
      thioredoxin reductase.
AB  - Human thioredoxin reductase was recently shown to contain a TGA encoded
      selenocysteine residue at the penultimate position of its amino acid chain.
      Depending on the availability of selenium during biosynthesis, an authentic
      selenocysteine-containing or a selenium-free enzyme truncated at the penultimate
      position is expected to be formed. Correspondingly, the enzymatic activity should
      be altered by selenium restriction, if the selenocysteine residue is functionally
      important. In order to check the catalytic role of the selenocysteine residue,
      four different human cell lines were grown in selenium deficient media or with
      adequate selenium supplementation (40 nM sodium selenite) and thioredoxin
      reductase activity was measured as NADPH-dependent DTNB reduction or thioredoxin
      mediated insulin reduction. Thioredoxin reductase activities, like glutathione
      peroxidase activities, were consistently higher in selenium supplemented cells,
      whereas glutathione reductase activity was not affected by the selenium. The dose
      response was similar for thioredoxin reductase and glutathione peroxidase, but
      the recovery of glutathione peroxidase activity upon selenium supplementation was
      faster than with thioredoxin reductase. Also the increase of glutathione
      peroxidase activities was substantially higher than that of thioredoxin reductase
      (400-1200% versus a maximum of 250%). These observations clearly indicate a
      catalytic role of the selenocysteine residue in the thioredoxin reductase, but
      suggest either the existence of a selenium-unresponsive isoenzyme or a residual
      disulfide reductase activity in the selenium-free truncated protein made under
      conditions of selenium deficiency.

PMID- 9288406
TI  - Farnesyl: proteintransferase inhibitors as agents to inhibit tumor growth.
AB  - Ras, a signal-transducing protein involved in mediating growth factor-stimulated
      proliferation, is mutationally activated in over 30% of human tumors. To be
      functional Ras must bind to the inner surface of the plasma membrane, with post
      translational lipid modifications being necessary for this localization. The
      essential, first modification of Ras is farnesylation catalyzed by the enzyme
      farnesyl: proteintransferase (FPTase). Inhibitors of FPTase (FTIs) are currently
      being tested to determine if they are capable of tumor growth inhibition. Here we
      describe our efforts, along with those of other groups, in testing the biological
      and biochemical effects of FTIs.

PMID- 9288407
TI  - Cellular regulation by protein phosphorylation: a historical overview.

PMID- 9288408
TI  - Event-related potentials in a passive and active auditory condition: effects of
      diazepam and buspirone on slow wave positivity.
AB  - The effects of single, oral doses of diazepam (10 mg), buspirone (10 mg) and
      placebo on auditory event-related potentials were assessed in healthy volunteers.
      Subjects received two series of auditory stimuli: a series of identical stimuli
      presented in a neutral, passive condition and a series of identical standard
      tones (P = 0.8), but now intermixed with target tones (P = 0.2), in an active,
      oddball condition. The analysis focused on the average value of the potential in
      two different phases, from 250 till 574 ms post-stimulus (including P300) and
      from 576 till 900 ms post-stimulus (including late slow wave positivity). Event
      related potentials for the standards of the oddball task were compared with the
      potentials of the same stimuli presented in the neutral condition. In addition,
      the classical comparison between the target and the standard in the oddball task
      was made. The first comparison was designed to isolate any effect of a change in
      the level of vigilance and attention due to involvement in the oddball task. This
      effect was evident as an increase in positivity that was smaller in the diazepam
      condition. The second comparison was designed to isolate the distinctive
      processing associated with task-relevant stimuli. This revealed that the P300 was
      reduced in the 250-574 ms window in the diazepam group. Both results suggest that
      cognitive processing of relevant stimuli is reduced by diazepam. Presumably, this
      is associated with the sedative effects of this drug. Consistent with this
      interpretation, subjects under the influence of diazepam made more omissions in
      the detection of targets in the oddball condition and had longer reaction times.
      In contrast to diazepam, the anxiolytic buspirone did not appear to have
      measurable effects on cognition.

PMID- 9288409
TI  - Biological determinants of P300: the effects of a barbiturate on latency and
      amplitude.
AB  - Polich & Kok (1995) (Biological Psychology, 41, 103-146) have recently argued
      that P300 is not only sensitive to specific 'cognitive' variables, but also to
      non-specific biological processes such as arousal. Fluctuations in arousal are
      said to be indexed by an inverse relationship between latency and amplitude. We
      tested this hypothesis with a drug that decreases arousal-the barbiturate
      secobarbital sodium. Twelve subjects performed a visual 80-20% oddball task at
      two levels of stimulus quality and after ingesting the drug (2.9 mg/kg body
      weight) or a placebo. Reaction time (RT) and P300 were collected simultaneously
      and the latter was analyzed on both a single trial and average basis. The RT
      results confirmed that secobarbital interacts with stimulus quality. Secobarbital
      slowed single trial P300 by about half as much as RT, and this slowing was
      additive with stimulus quality. Thus the two measures dissociated. Secobarbital
      did not influence P300 amplitude. Average P300 revealed the same pattern of
      results, although the size of the latency effects was somewhat attenuated. RT and
      P300 latency were more strongly correlated than P300 latency and amplitude. We
      propose that P300 latency reflected the slowing of stimulus evaluation produced
      by the depressant properties of the drug, and that fluctuations in arousal are
      not necessarily associated with a simple inverse relationship between P300
      latency and amplitude.

PMID- 9288410
TI  - Rate effect and mismatch responses in the somatosensory system: ERP-recordings in
      humans.
AB  - In the first experiment, somatosensory event-related potentials (SERPs) were
      recorded to tactile pulses and vibration bursts applied to the left middle finger
      in trains of 4-8 stimuli with 1 s intervals. In addition to the negative N140
      deflection, also the positive P50, P100 and P300 waves attenuated in amplitude
      with stimulus repetition. These decreases were immediate, there being no marked
      further amplitude attenuation after the second stimulus. The locus of this rate
      effect appears not to be the primary SI or SII, but rather prefrontal cortices or
      some deeper structures. In the second experiment, vibratory stimuli of different
      frequencies or at different skin sites were presented using the oddball paradigm.
      When the deviant stimulus was a high-frequency vibration burst, it elicited a
      distinct N250 deflection, probably analogous to the auditory N2b. When the
      deviation was a change in the stimulation site, no N250 deflection but instead an
      extra negativity between 100-200 ms latency, probably analogous to the auditory
      mismatch negativity, was observed.

PMID- 9288411
TI  - Brain potentials elicited by words: word length and frequency predict the latency
      of an early negativity.
AB  - Prior work has suggested that open- and closed-class words elicit negative
      components in the event-related potential (ERP) that differ in timing and scalp
      distribution. We tested this hypothesis against the possibility that the word
      class effects are attributable to quantitative differences in word length and
      frequency. Event-related brain potentials (ERPs) were recorded from 13 scalp
      sites while participants read normal or scrambled prose. ERPs were averaged as a
      function of word class (open vs. closed) and grammatical category (articles,
      nouns, verbs, etc.). Regression analyses indicated that the latency of an early
      occurring negative component was highly correlated with the mean length and
      normative frequency of words in each grammatical category. Stronger correlations
      were observed in the scrambled prose condition than in the normal prose
      condition. Differences in the scalp distributions of these negativities were
      found to be a function of grammatical category rather than word class. These
      results are taken to be inconsistent with the claim that open- and closed-class
      words elicit qualitatively distinct negativities.

PMID- 9288412
TI  - Effects of body core temperature and brain dopamine activity on timing processes
      in humans.
AB  - In a placebo-controlled study, the effects of experimentally induced increase in
      body core temperature and of the dopamine antagonist haloperidol on judgments of
      an apparent second, a speeded-tapping task, and temporal discrimination of
      intervals in the range of milliseconds and seconds were investigated in 40
      healthy male subjects. A 0.7 degree C-increase in body core temperature due to 3
      h exposure to an ambient temperature of 52 degrees C did not cause any
      statistically significant changes in timing tasks. Unlike heat exposure, 3 mg of
      haloperidol caused a pronounced impairment of performance on the temporal
      discrimination of intervals in the range of milliseconds and seconds (P < 0.01
      and P < 0.001, respectively) as well as speeded tapping (P < 0.05). For temporal
      discrimination of intervals in the range of seconds, a significant interaction
      between ambient temperature and haloperidol could be established (P < 0.05)
      indicating that haloperidol caused a significant performance decrement only in
      subjects exposed to an ambient temperature of 28 degrees C but not in those
      exposed to 52 degrees C. The overall pattern of results suggests that temporal
      processing of intervals in the range of milliseconds can be considered a function
      of dopaminergic activity in the basal ganglia while temporal processing of longer
      intervals appears to be cognitively mediated. Furthermore, the hypothesis that
      timing processes in humans are modulated by changes in body core temperature
      could not be established.

PMID- 9288414
TI  - Morphology and distribution of pit organs and canal neuromasts in non-teleost
      bony fishes.
AB  - The morphology of the pit organs and canal neuromasts of the actinopterygian
      Polypterus and the lungfishes Lepidosiren, Neoceratodus and Protopterus are
      described using light microscopy, scanning electron microscopy and transmission
      electron microscopy. Pit organs resemble canal neuromasts in their hair cell
      polarization, but they differ in size, shape, hair cell density and in the length
      of the kinocilia. Pit line neuromasts in Lepidosiren, Polypterus and Protopterus
      are arranged in dense lines, with numerous neuromasts between pores in the canal,
      and are an order of magnitude smaller than canal neuromasts in Polypterus. We
      suggest that the evolutionary transformation of canal neuromasts into superficial
      neuromasts occurred through the evolutionary reduction of the lateral line
      canals, either as the result of selection for changes in neuromast function, or
      as the result of non-adaptive reduction of dermal bone around the lateral line
      canals and their neuromasts. Protopterus (a lepidosirenid lungfish) is apparently
      unique among bony fishes in that it has multiple neuromasts between adjacent
      pores in lateral line canals on the head. An analysis of the distribution of this
      character among major gnathostome clades indicates that multiple canal neuromasts
      between pore positions is a primitive gnathostome character. Latimeria,
      Neoceratodus and actinopterygian fishes are characterized by an alternative
      character state, the presence of one canal neuromast between adjacent pores.

PMID- 9288413
TI  - Immunoreactive gonadotropin-releasing hormone (GnRHir) is associated with
      vestibular structures in the green anole (Anolis carolinensis).
AB  - The distribution of immunoreactive gonadotropin-releasing hormone (GnRHir) in
      relation to endocrine and behavioral pathways is not well established for
      lizards. To more completely understand the GnRHir distribution and its possible
      function in a lizard, we investigated the brain of Anolis carolinensis, a species
      whose visual courtship displays, mating postures and gonadal cycles are well
      known. Using antisera that recognize multiple GnRH forms, we observed no GnRHir
      cells or fibers in the forebrain. In the midbrain, however, GnRHir cells occurred
      along the medial border of the medial longitudinal fasciculus. These cells
      appeared to project GnRHir fibers to nuclei of cranial nerve III and IV. In the
      hindbrain, positive fibers were observed in the area of the vestibular nuclei and
      dorsal funiculus. These hindbrain fibers were followed to their terminals in the
      cerebellum. The GnRHir midbrain distribution suggests an association of GnRH with
      eye movements, whereas the hindbrain distribution suggests a GnRH-vestibular
      association. The lack of GnRHir in the forebrain of Anolis could reflect the
      minimal role of the vomeronasal system in mediating reproduction in this species.
      Thus, our study cannot verify hypothalamic GnRH control of the pituitary in A.
      carolinensis, but it does indicate GnRH control of oculomotor and vestibular
      nuclei, which might play a role in Anolis reproductive behaviors.

PMID- 9288415
TI  - The distribution of reduced nicotinamide adenine dinucleotide phosphate
      diaphorase in the leopard frog telencephalon and related projections.
AB  - The distribution of reduced nicotinamide adenine dinucleotide phosphate
      diaphorase (NADPH-D) was mapped histochemically in the forebrain of Rana pipiens,
      the leopard frog. Intense staining was observed which was strikingly restricted
      to certain nuclear groups and fiber tracts. The densest concentrations of NADPH-D
      stained cell bodies and fibers were observed in the granule layer of the
      accessory olfactory bulb and in the ventral aspect of the lateral pallium.
      Intense staining has also been reported in the presumed mammalian homologues of
      these regions. Less densely packed clusters of intensely stained neurons were
      found in the striatum, the anterior entopeduncular nucleus, the olfactory
      tubercle and the pars lateralis of the amygdala, whereas the preoptic region and
      the medial septum exhibited dense accumulations of lightly stained cells. Several
      fiber systems or terminal fields could be detected, including a ring of heavy
      staining which enclosed the striatum and an apparent terminal field in the
      lateral part of the medial pallium. A prominent compact tract, which may be
      homologous to a component of the stria terminalis of mammals, could be also
      followed from the ventral portion of the lateral pallium to the infundibular
      hypothalamus.

PMID- 9288416
TI  - Microhabitat use, trophic patterns, and the evolution of brain structure in
      African cichlids.
AB  - The species assemblages of cichlids in the three largest African Great Lakes are
      among the richest concentrations of vertebrate species on earth. The faunas are
      broadly similar in terms of trophic diversity, species richness, rates of
      endemism, and taxonomic composition, yet they are historically independent of
      each other. Hence, they offer a true and unique evolutionary experiment to test
      hypotheses concerning the mutual dependencies of ecology and brain morphology. We
      examined the brains of 189 species of cichlids from the three large lakes:
      Victoria, Tanganyika, and Malawi. A first paper demonstrated that patterns of
      evolutionary change in cichlid brain morphology are similar across taxonomic
      boundaries as well as across the three lakes [van Staaden et al., 1995 ZACS 98:
      165-178]. Here we report a close relationship between the relative sizes of
      various brain structures and variables related to the utilization of habitat and
      prey. Causality is difficult to assign in this context, nonetheless, prey size
      and agility, turbidity levels, depth, and substrate complexity are all highly
      predictive of variation in brain structure. Areas associated with primary sensory
      functions such as vision and taste relate significantly to differences in feeding
      habits. Turbidity and depth are closely associated with differences in eye size,
      and large eyes are associated with species that pick plankton from the water
      column. Piscivorous taxa and others that utilize motile prey are characterized by
      a well developed optic tectum and a large cerebellum compared to species that
      prey on molluscs or plants. Structures relating to taste are well developed in
      species feeding on benthos over muddy or sandy substrates. The data militated
      against the existence of compensatory changes in brain structure. Thus enhanced
      development of a particular function is generally not accompanied by a parallel
      reduction of structures related to other modalities. Although genetic and
      environmental influences during ontogeny of the brain cannot be isolated, this
      study provides a rich source of hypotheses concerning the way the nervous system
      functions under various environmental conditions and how it has responded to
      natural selection.

PMID- 9288417
TI  - From genetic research to new thoughts about evaluating psychotherapy: child
      psychiatry approaches the year 2000.

PMID- 9288419
TI  - Severe conduct disorder--some key issues.
AB  - OBJECTIVE: To examine the state of knowledge about clinically severe conduct
      disorder and identify key issues. METHOD: This paper surveys the literature on
      conduct disorder and delineates and discusses the critical issues. RESULTS:
      Conduct disorder is the subject of a vast and growing amount of research on
      taxonomy, correlates, etiology, outcome, management, and prevention. There are 2
      distinctive types: childhood and adolescent onset. Comorbidity with other
      disorders is common. It remains a costly disorder, however, with a generally poor
      prognosis for the childhood-onset type. The validity of the separation of conduct
      and antisocial personality disorder is questionable. CONCLUSIONS: In view of its
      huge cost, chronicity, and generally poor outcome, childhood-onset or severe
      conduct disorder should be considered one of if not the major public health
      problems of our time, and resources for its study and management should reflect
      this. The disorder is poorly defined and inadequately studied in females.

PMID- 9288418
TI  - Implications of genetic research for child psychiatry.
AB  - OBJECTIVE: To review implications of genetic research in child psychiatry.
      METHOD: Key advances in quantitative and molecular genetics are noted and
      findings are summarized with respect to autism, attention-deficit hyperactivity
      disorder, oppositional defiant and conduct disorders, depression, schizophrenia,
      and Tourette's syndrome. CONCLUSIONS: Genetic findings will be helpful clinically
      in the elucidation of disordered brain processes, the understanding of nature
      nurture interplay, diagnosis, genetic counselling, and pharmacotherapy.

PMID- 9288420
TI  - Evaluating the effectiveness of interventions in child psychiatry.
AB  - OBJECTIVE: To review the nature of outcome measures used to evaluate psychosocial
      treatment in children. METHOD: Recent research findings that highlight the
      importance of outcome data and justify randomized controlled trials (RCTs) are
      reviewed. RESULTS: Outcome measures of child therapy can focus on changes in the
      child's symptoms, adaptation to the psychosocial environment, cognitive or
      emotional capacities, and changes in interaction with others. They can also
      assess service utilization, related costs, and the suffering of those associated
      with the child before and after treatment. RCTs remain the optimal methodology,
      notwithstanding current critiques. CONCLUSION: Studies assessing the
      effectiveness of psychosocial treatment must include a definition of various
      outcomes and use appropriate methodologies to measure them.

PMID- 9288421
TI  - Psychotherapy outcome research in child psychiatric disorders.
AB  - OBJECTIVE: To compile, review, and comment upon the application of psychotherapy
      to the treatment of psychiatric disorders first appearing in childhood and
      adolescence. METHOD: Representative research papers published over the past 4
      decades on the subject of psychotherapy of children and adolescents were
      compiled. Selection for inclusion in this review was based upon salience to the
      subject of treatment of child psychiatric disorders. Special consideration was
      given to large-scale and metaanalytic studies, as well as to studies comparing
      psychotherapy with other forms of treatment. RESULTS: There is mixed evidence for
      the efficacy of psychotherapy for child psychiatric disorders. There are few
      direct comparisons between treatment modalities in the child psychiatric
      literature. Methodological problems include a history of theoretical development
      of therapies without reference to current conceptions of mental illness, a
      paucity of direct comparisons among psychotherapies and between psychotherapy and
      other psychiatric treatments, inconsistent definition of psychotherapy from study
      to study, and inconsistency in stated outcome measures. In general, cognitive
      behavioural therapies performed better in application to child psychiatric
      disorders than did insight-oriented therapies. CONCLUSIONS: Outcome research in
      child-oriented psychotherapy is still in its infancy. There are simply too few
      studies of many therapies and many conditions to draw firm conclusions about
      efficacy. More work is needed in matching discrete, consistently applied
      therapies to selected psychiatric pathologies. Questions regarding
      psychotherapy's potential application to prevention of mental illness and to
      management of distress surrounding mental illness (as distinct from treatment of
      the illness itself) remain to be answered.

PMID- 9288422
TI  - Are there injury-prone children? A critical review of the literature.
AB  - OBJECTIVES: To review the evidence of general injury and pedestrian injury
      studies to determine if there are child behavioural, emotional, developmental, or
      physical characteristics that put children at higher risk for injury and, if
      there are such proneness risk factors, to determine their importance relative to
      other risk factors. METHODS: This paper critically assesses 11 general child
      injury studies and 6 child pedestrian injury studies that have examined variables
      of child proneness. Information on study design, source of data, magnitude and
      significance of the risk factors identified, and study limitations are presented
      in separate sections. RESULTS: A critical review of the literature suggests that
      aggression is a consistent risk factor for general injuries but not for
      pedestrian injuries, hyperactivity is inconsistently associated with all types of
      injuries, and both a general measure of behaviour problems and a measure of
      unsafe behaviour were found to be significantly related to pedestrian injuries. A
      look at the pedestrian injury literature suggests that child risk factors make a
      consistent but minor contribution to injuries in comparison with environmental
      and social risk factors. CONCLUSIONS: We need to address the environmental and
      social risk factors by educating parents about the roles of home stressors, poor
      supervision, and high-risk exposure in child injuries and by adding our voice to
      the efforts to bring into effect engineering and legislative interventions.

PMID- 9288423
TI  - Posttraumatic stress symptoms and medical procedures in children.
AB  - OBJECTIVE: To focus on posttraumatic stress symptoms after childhood diseases
      such as cancer, organ transplantation, and severe burns. METHODS: Differential
      diagnoses, risk factors, and treatment aspects (psychological and
      pharmacological) are discussed. RESULTS: The concept of adjustment problems in
      chronic or severe illnesses is widely used in pediatrics. Many aspects of severe
      childhood diseases are traumatic, as defined by the DSM-IV: severe illnesses are
      life-threatening, medical procedures threaten the child's physical integrity, and
      disorganized behaviour periods are common. CONCLUSION: This concept, which
      remains insufficiently investigated, is a promising area of investigation for
      prospective and prevention studies.

PMID- 9288424
TI  - The delusional parent: family and multisystemic issues.
AB  - OBJECTIVES: To examine the dilemmas for children, family, and mental health
      professionals posed by the presence of a delusional parent in a family, including
      someone with induced psychotic disorder (IPD); to identify frequently
      unrecognized problems; and to propose practical suggestions for professionals.
      METHOD: The pertinent literature on the effects of delusional parents on
      children, families, and professionals is reviewed. By way of 3 case vignettes,
      the dilemmas are identified and discussed. RESULTS: Delusional disorders are
      underdiagnosed, resulting in poor anticipation of their implications.
      Unanticipated family factors, such as "pursuit of isolation" and the related
      heightened risk of violence, contribute to the failure of professional
      interventions, which has been described as "therapeutic systems paralysis."
      CONCLUSIONS: These cases are complex, often requiring multisystemic involvement
      to reduce the risks of flight. violence, psychosis, posttraumatic stress
      disorder, and other psychiatric sequelae to children and other family members.
      The critical features of the innovative collaboration ("therapeutic consensus")
      required between professionals for successful therapeutic interventions with
      these families are described.

PMID- 9288425
TI  - Children of parents with bipolar disorder: a metaanalysis of risk for mental
      disorders.
AB  - OBJECTIVE: To compare the prevalence rates of mental disorders among children of
      parents with bipolar disorder and of parents with no mental disorders. METHOD:
      Seventeen studies, meeting specific selection criteria, were included in the
      metaanalyses. Risks for mental disorders among children were estimated by
      aggregating raw data from the selected studies. RESULTS: Results indicate that in
      comparison with children of parents with no mental disorders, children of parents
      with bipolar disorder are 2.7 times more likely to develop any mental disorder
      and 4.0 times more likely to develop an affective disorder. The metaanalyses
      indicate that during childhood and adolescence, the risks for any mental disorder
      and for affective disorders in children are consistently but moderately related
      to having a parent who suffers from bipolar disorder. CONCLUSIONS: Risk factors
      that could account for the psychopathology observed in children of bipolar
      parents are explored.

PMID- 9288426
TI  - Bipolar disorder in children and adolescents: current challenges.
AB  - OBJECTIVE: To demonstrate the diagnostic and treatment challenges in juvenile
      onset bipolar disorder. METHOD: Three case vignettes are outlined to demonstrate
      different bipolar presentations in children and adolescents. RESULTS: These case
      examples illustrate important issues in the diagnosis and management of juvenile
      onset bipolar disorder. These issues include diagnostic confusion with atypical
      initial presentation and the effect of developmental factors on symptom
      expression. The relationship among genetic risk, early affective instability, and
      the stress generated by affectively ill family members is complex and circular.
      Comorbidity with disruptive behaviour disorders, as well as anxiety disorders, is
      demonstrated by the cases discussed. Comorbid disorders may affect outcome and
      require separate treatment intervention. There is evidence for the prophylactic
      antimanic effect of lithium carbonate in children and adolescents, but its
      specificity as an antimanic agent is still uncertain. There is less evidence, at
      present, for effectiveness of other mood stabilizers in this age group, although
      sodium valproate may prove more effective in mixed mania and rapid cycling, which
      are so often seen with early-onset bipolar disorder. CONCLUSIONS: While the
      existence of juvenile-onset bipolar disorder is no longer in dispute, several
      outstanding issues related to diagnosis and long-term management remain. Careful
      prospective research will be necessary to sort out these issues definitively.

PMID- 9288427
TI  - The treatment of conduct disorder: perspectives from across Canada.
AB  - OBJECTIVE: To provide a synopsis of treatment programs for conduct-disordered
      children in Canada. METHOD: Five groups of authors from British Columbia,
      Ontario, Quebec, and New Brunswick describe their approaches to the treatment of
      children with conduct disorder. RESULTS: All programs emphasize the needs to use
      multimodal treatment schemes, including day and short-term residential care, and
      to base programs on identified factors associated with the development of conduct
      disorder. CONCLUSION: Specific forms of treatment of conduct disorder are
      promising but are often hampered by social and political agendas.

PMID- 9288428
TI  - Judicial case management and the custody and access assessment: melding the
      approaches.
AB  - BACKGROUND: The presence of the Unified Family Court, with procedures emphasizing
      judicial case management and settlement in custody disputes, provided an
      opportunity to combine these practices with those of a university hospital-based
      family court clinic experienced in the provision of custody assessments.
      Specifically, a process integrating the clinical custody assessment with the work
      of counsel and court procedures was developed. This format, incorporating the
      preparation of a clinical settlement conference brief, was then evaluated with
      emphasis on time management, outcome in relation to settlement or trial, and the
      effect of clinical assessment at critical points in the combined endeavour.
      METHOD: Seventy-two judicial referrals conducted using this format were reviewed.
      To assess efficiency, we determined time intervals to various points in the
      process and compared them to previous local practice. Settlement rates, recorded
      incrementally to mark each component's contribution, were compared with rates
      noted in the literature. Assessment functions were identified according to the
      point of resolution of the dispute and in a manner to facilitate comparison with
      previously published work. RESULTS: The format resulted in 50% of cases settling
      without trial in under 5 months, a minimum settlement rate of 50%, and confirmed
      the ability of clinical assessment to contribute flexibly to dispute resolution
      in several conciliation venues and at trial. CONCLUSIONS: Combining legal and
      mental health efforts can results in more efficient use of resources and a
      substantial diversion of cases from continuing litigation. While altering the
      process of clinical assessments enhances such findings, further work is required
      to assure appropriate selection criteria for various intervention formats.

PMID- 9288429
TI  - Child psychiatric consultation service to community agencies: a collaborative
      approach involving three community agencies.
AB  - OBJECTIVE: To report the early experience of a multiagency child psychiatric
      consultation service. METHOD: The program is described, and the demographic
      characteristics of clients referred to the consultation program over the first 25
      months of operation are presented. Referrals were examined for demographics and
      the questions consultees wanted to have answered. RESULTS: In 59 of 100
      consultations, physical and/or sexual abuse was proved or highly suspected. In 82
      of the 100 cases, consultees had questions pertaining to management issues.
      Questions related to diagnostic issues numbered 62, and there were 45 questions
      about safety issues. CONCLUSION: Effective psychiatric consultations services to
      rural areas can be established. Once established, the questions of consultees can
      provide an effective training ground for future community-oriented child
      psychiatrists.

PMID- 9288430
TI  - Re: A time to bury tricyclic antidepressants or to praise them?

PMID- 9288431
TI  - Evaluation of children's social skills groups using self-report measures with
      children and parents.

PMID- 9288432
TI  - Depression in a 13-year-old child: a near miss.

PMID- 9288433
TI  - The "delirium" of delusional misidentification: implications for the
      classification of delusional misidentification syndromes.

PMID- 9288435
TI  - Couples communication skills training for schizophrenia.

PMID- 9288436
TI  - A possible new treatment approach to obsessive-compulsive disorder.

PMID- 9288434
TI  - Spiramycin-associated acute dystonia during neuroleptic treatment.

PMID- 9288437
TI  - Treatment of the mentally ill physician.

PMID- 9288438
TI  - The foundations of effective management of bipolar disorder.
AB  - OBJECTIVES: To understand the epidemiology and course of bipolar disorder; to
      outline the importance of accurate and reliable diagnosis of bipolar disorder
      both on a cross-sectional and longitudinal basis; and to emphasize the value of a
      collaborative therapeutic relationship, psychoeducation, and psychotherapy.
      METHODS: A brief review of relevant literature to deal with the issues of
      diagnosis and laying the foundations for effective treatment. RESULTS: Bipolar
      disorder may well be a heterogeneous group of conditions with varying forms of
      biphasic mood dysregulation and a changing course across a lifetime. A
      collaborative therapeutic relationship, psychoeducation, and psychotherapy can be
      the basis for effective management. CONCLUSIONS: As the concept of bipolar
      disorder has broadened, the condition is being identified with increasing
      frequency in many clinical settings. It is a relapsing and recurring condition.
      It is now recognized that in addition to rational pharmacotherapy, there is a
      need to encourage a high level of treatment adherence while providing a holistic
      package of interventions.

PMID- 9288439
TI  - Psychosocial interventions as an adjunct to pharmacotherapy in bipolar disorder.
AB  - OBJECTIVE: To summarize the evidence and make treatment recommendations regarding
      the use of psychosocial interventions as an adjunct to pharmacotherapy for
      bipolar disorder. METHODS: We reviewed published outcome studies since 1975
      identified in MEDLINE and PsychLIT searches. RESULTS: Available studies are
      initial and of highly variable methodological rigour. Evidence is most robust for
      the efficacy of psychoeducation and family therapy, and these received the
      highest level of recommendation as interventions. Group therapy, cognitive
      behavioural therapy, and behavioural family management therapy are supported by
      weaker evidence and received a lower-level treatment recommendation. Availability
      of only a single interpersonal and social rhythms therapy trial limited the
      confidence of the recommendation for this intervention. CONCLUSIONS: Controlled
      trials are needed to replicate early outcome studies and guide treatment
      recommendations. Accumulated evidence of favourable psychosocial intervention
      outcomes supports, with variable confidence, their use as adjuncts to
      pharmacotherapy in the treatment of bipolar disorder.

PMID- 9288440
TI  - Treatment of mania, mixed state, and rapid cycling.
AB  - OBJECTIVES: To summarize the quality of evidence for the efficacy of different
      biological treatments in mania, mixed state, and rapid cycling and to propose
      guidelines for treatment of these conditions. METHOD: Articles published on
      treatment of acute mania, mixed states, and rapid cycling were reviewed and rated
      for quality of evidence using Periodic Health Examination guidelines. RESULTS:
      Lithium and divalproex sodium are effective in classical pure mania, whereas
      divalproex sodium and carbamazepine are likely more effective in mixed states.
      Divalproex sodium is likely more efficacious than carbamazepine and lithium when
      the mania is part of a rapid-cycling course. Typical neuroleptics are efficacious
      in acute mania, particularly in the presence of marked psychotic symptoms.
      Atypical neuroleptics can be useful in refractory mania. Some benzodiazepines do
      have antimanic effects, but they are increasingly being shown to have usefulness
      as adjuncts to mood stabilizers or neuroleptics rather than as primary antimanic
      agents. Electroconvulsive therapy (ECT) is an efficacious and broad-spectrum
      treatment. CONCLUSIONS: Mania can present with or without mood-congruent or mood
      incongruent psychotic features and as part of a rapid-cycling or nonrapid-cycling
      course. Mixed state is a common presentation in an acutely manic patient. The
      accurate assessment of these issues can serve as a guide in determining treatment
      options and choices.

PMID- 9288441
TI  - Bipolar depression: treatment options.
AB  - OBJECTIVE: To review studies on treatments for bipolar depression and make
      recommendations for practising clinicians treating patients with bipolar
      depression. METHOD: Studies that examined various treatments for bipolar
      depression were evaluated and rated for evidence of efficacy using Periodic
      Health Examination criteria. The rating for classification of recommendation for
      an intervention was made taking both the efficacy and the side effects into
      consideration. RESULTS: Mood stabilizers, cyclic antidepressants, monoamine
      oxidase inhibitors (MAOIs), and electroconvulsive therapy (ECT) are all effective
      in treating bipolar depression. Almost all antidepressant treatments with the
      exception of mood stabilizers have been reported to induce a manic-hypomanic
      switch and rapid cycling. CONCLUSIONS: Mood stabilizers, lithium in particular,
      are recommended as the first-line treatment. Addition of a second mood stabilizer
      or a cyclic antidepressant would be an appropriate next step. Newer agents such
      as lamotrigine offer considerable promise in treating bipolar depressed patients.

PMID- 9288442
TI  - Continuation and prophylactic treatment of bipolar disorder.
AB  - OBJECTIVES: To summarize the evidence for efficacy from published literature of
      biological treatments in the continuation and maintenance phases of bipolar
      disorder, as well as the recommendations about different treatment options made
      by the working group within the Bipolar Sub-Committee of the Canadian Network for
      Mood and Anxiety Treatments (CANMAT). METHODS: A review of relevant published
      literature and proceedings of international conferences was conducted. The
      quality of evidence was assessed and classified according to the Periodic Health
      Examination criteria. Treatment recommendations of the working group were based
      on quality of evidence, a consensus of expert views, and the opinions of
      psychiatrists and family physicians from across Canada. RESULTS: There is
      overwhelming evidence for the efficacy of lithium in the prophylaxis of bipolar
      disorder. The evidence for carbamazepine is less robust. There are no published
      double-blind studies with adequate numbers of subjects treated with divalproex
      sodium. CONCLUSIONS: During and at the end of the continuation phase it is
      recommended that mood stabilizers should remain the mainstay of therapy and that
      other treatments should be gradually discontinued or maintained only if there is
      valid reason to do so. Efficacious maintenance treatment can reduce morbidity and
      mortality significantly and improve patients' quality of life.

PMID- 9288443
TI  - Tropical sprue and subclinical enteropathy: a vision for the nineties.
AB  - Aside from infectious intestinal diseases with known etiology, there is a group
      of gastrointestinal disorders mainly affecting the small intestine of individuals
      predominantly living in and less often visiting or returning from the Third
      World, usually the tropics, and ranging from asymptomatic structural and/or
      functional abnormalities of the gastrointestinal mucosa (subclinical enteropathy,
      SE) to a fully symptomatic condition highlighted by malabsorption of nutrients
      with associated nutritional deficiencies responsive to folate and broad spectrum
      antibiotic treatment (tropical sprue, TS). Mounting evidence supports an
      infectious cause in many instances. The exact nature of the infection, whether
      initiated and/or perpetuated by enterotoxigenic coliform bacteria, virus(es) or a
      combination of these, is not clear. Further studies, including those using
      molecular techniques, are needed in order to clarify various aspects of these
      widely prevalent disorders.

PMID- 9288444
TI  - Candidate genes, small effects, and the prediction of atherosclerosis.
AB  - Atherogenesis is a complex process that involves the contributions of several
      pathophysiological subsystems. The dissection of the genetic component of
      atherosclerosis has become possible using current molecular technologies and
      analytical methods. Genetic factors are considered to determine the limits under
      which atherosclerosis develops and environmental factors are considered to
      position an individual's risk within these limits. Atherosclerosis proceeds
      through a well-characterized series of pathological stages that involve key cell
      types and the expression of particular gene products. Reductionist experimental
      models have helped to produce a list of several hundred candidate genes for the
      study of the genetic component of atherosclerosis. Within certain families and
      isolated communities, the effect of a single candidate gene on atherosclerosis
      susceptibility may be profound, as in the case of mutations in the gene encoding
      the low-density lipoprotein receptor, which produce familial hypercholesterolemia
      and premature atherosclerosis. However, particular candidate genes have small
      effects on atherosclerosis, or to one of its intermediate phenotypes, in whole
      populations. In addition, pleiotropy and epistasis can confound the
      identification of the genetic component of atherosclerosis. Despite these
      limitations, it might still be possible to use genetic information clinically in
      order to classify individuals who are susceptible to atherosclerosis, especially
      if as-yet undiscovered candidate genes, which are found to be important
      determinants of disease. However, it will be impossible to predict the onset of a
      clinical manifestation of atherosclerosis in a particular person. This is due to
      the confounding influence of other forces, such as variations in interindividual
      environmental landscape, nonlinear interactions between genes and environment,
      and even the possible influence of biological chaos.

PMID- 9288445
TI  - The toxicology of mercury.
AB  - The major physical forms of mercury to which humans are exposed are mercury
      vapor, Hg0, and methylmercury compounds, Ch3HgX. Mercury vapor emitted from both
      natural and anthropogenic sources is globally distributed in the atmosphere. It
      is returned as a water-soluble form in precipitation and finds its way into
      bodies of fresh and ocean water. Land run-off also accounts for further input
      into lakes and oceans. Inorganic mercury, present in water sediments, is subject
      to bacterial conversion to methylmercury compounds that are bioaccumulated in the
      aquatic food chain to reach the highest concentration in predatory fish. Human
      exposure to mercury vapor is from dental amalgam and industries using mercury.
      Methylmercury compounds are found exclusively in seafood and freshwater fish. The
      health effects of mercury vapor have been known since ancient times. Severe
      exposure results in a triad of symptoms, erethism, tremor, and gingivitis. Today,
      we are concerned with more subtle effects such as preclinical changes in kidney
      function and behavioral and cognitive changes associated with effects on the
      central nervous system. Methylmercury is a neurological poison affecting
      primarily brain tissue. In adults, brain damage is focal affecting the function
      of such areas as the cerebellum (ataxia) and the visual cortex (constricted
      visual fields). Methylmercury also at high doses can cause severe damage to the
      developing brain. Today the chief concern is with the more subtle effects arising
      from prenatal exposure such as delayed development and cognitive changes in
      children.

PMID- 9288446
TI  - Vitamin C in human and guinea pig aqueous, lens and plasma in relation to intake.
AB  - PURPOSE: Given the recent correlation between nutrition and risk for eye disease,
      there is keen interest in a possible correlation between nutrient intake and eye
      tissue nutrient levels. In this work, the objective was (1) to determine, for the
      first time, the relation between dietary intake of vitamin C and eye tissue
      levels of the vitamin in free-living humans, (2) to determine the relation
      between levels of the vitamin in plasma, lens and aqueous, and (3) to compare
      this information to data gathered for a carefully reared group of guinea pigs
      that were fed different levels of vitamin C. METHODS: Two hundred sixty-five
      cataract patients (mean age = 72 years) from a clinical practice were recruited
      for this study. One hundred thirty-two patients provided the dietary intake data
      via a food frequency questionnaire, which we used for this work. Plasma, aqueous
      humor, and lens samples were obtained at the time of lentectomy and preserved for
      vitamin C analysis. Comparable samples were obtained from male Hartley white
      guinea pigs that were fed known amounts of vitamin C. Linear and log10-linear
      statistical models were also used to characterize the relation between vitamin C
      intake and human ocular tissue levels of the vitamin and to examine potential
      confounding and the effect of modification by age and sex. RESULTS: In humans,
      plasma and aqueous vitamin C concentrations were related to intake in a log
      linear fashion, with slopes of 0.03 mM plasma vitamin C/log10-mg daily vitamin C
      intake and 0.41 mM aqueous vitamin C/log10-mg daily vitamin C intake. The best
      fit of vitamin C levels in lens and diet predicts a linear relationship with a
      sex-adjusted slope of 0.00094 mM lens vitamin C/mg daily vitamin C intake,
      although a log-linear relation can also be modeled. In guinea pigs, diet was
      related to eye tissue and plasma levels of the vitamin by a log10 linear
      relationship in all cases. Vitamin C in human lens was linearly related to plasma
      and aqueous vitamin C with slopes of 8.8 and 0.23, respectively. Vitamin C in
      aqueous was related to plasma in a log10-linear fashion with a slope of 1.6 mM
      aqueous vitamin C/log10 mM plasma vitamin C. In guinea pigs, vitamin C in plasma
      was related to aqueous and lens vitamin C by log10-linear relationships, whereas
      lens and aqueous vitamin C were clearly linearly related. CONCLUSIONS: Plasma and
      aqueous appear to be saturated in humans with intakes of < 250 mg vitamin C/day.
      However, a saturating relationship between lens vitamin C and dietary intake in
      humans was not indicated in this study, although such a relationship is seen in
      guinea pigs. Intertissue relations between vitamin C levels in humans and guinea
      pigs are similar for some but not all relations.

PMID- 9288447
TI  - Uveitis in the southeastern United States.
AB  - PURPOSE: Previous epidemiologic studies of uveitis have focused on predominantly
      Caucasian populations, and none have been based in the Southeast. We analyzed the
      epidemiology of uveitis among a referral population with a high percentage of
      African Americans in the United States. METHODS: We evaluated demographic data
      from 385 consecutive patients referred to the Duke Uveitis Clinic. RESULTS: Of
      the 385 patients, 120 (31%) were African American and 258 (67%) Caucasian; 237
      (62%) were female and 148 (38%) male. The most common diagnoses among the 385
      patients were idiopathic panuveitis (64 patients [17%]), idiopathic anterior
      uveitis (47 patients [12%]), pars planitis (46 patients [12%]), sarcoidosis (44
      patients [11%]), and toxoplasmosis (39 patients [10%]). These diagnoses were also
      the most common among the 120 African American patients: 33 patients (28%) had
      idiopathic panuveitis, 30 (25%) had sarcoidosis, 10 (8%) had idiopathic anterior
      uveitis, 8 (7%) had toxoplasmosis, and 6 (5%) had pars planitis. Among the 258
      Caucasian patients, the most common diagnoses were pars planitis (39 patients
      [15%]), idiopathic anterior uveitis (37 patients [14%]), toxoplasmosis (30
      patients [12%]), idiopathic panuveitis (28 patients [11%]), and multifocal
      choroiditis and panuveitis (MCP) (17 patients [7%]). Categorizing diagnoses of
      all 385 patients by anatomic location, panuveitis was most frequent (148 patients
      [38%]), followed by anterior uveitis (97 patients [25%]), posterior uveitis (93
      patients [24%]), and intermediate uveitis (47 patients [12%]). CONCLUSIONS: The
      higher frequency of sarcoidosis and idiopathic panuveitis than previously
      reported is related to our larger African American population base. The racial
      composition of the Southeast does not, however, account for differences such as
      our higher percentage of MCP; it is possible that other genetic or environmental
      factors play a role in this region.

PMID- 9288448
TI  - Concentrations of adenosine and its metabolites in the rat retina/choroid during
      reperfusion after ischemia.
AB  - PURPOSE: Little is known about the nature of biochemical disturbances during
      reperfusion after retinal ischemia. Previous studies have suggested that
      adenosine is responsible for regulation of retinal blood flow soon after ischemia
      has ended. Therefore, in this study we measured concentrations of adenosine and
      its metabolites in the rat retina/choroid after brief (10 min) or prolonged (60
      min) periods of ischemia, and the functional consequences of inhibiting adenosine
      metabolism. METHODS: Ischemia was produced in anesthetized rats by ligation of
      the central retinal artery. The eyes were frozen in situ and purine nucleoside
      concentration was determined by high performance liquid chromatography. The
      functional effects of pre-ischemic inhibition of xanthine dehydrogenase/xanthine
      oxidase were assessed by measurement of the electroretinogram before, during, and
      up to 7 days following 60 min ischemia. RESULTS: Changes in the concentrations of
      adenosine and its metabolites were significant early in the reperfusion period,
      and were greater in magnitude and occurred earlier in prolonged, compared to
      brief, ischemic periods. Concentrations of adenosine, inosine, and hypoxanthine
      remained elevated for 30 min following the end of 60 min ischemia, and xanthine
      concentration was significantly elevated until 60 min after the end of either 10
      or 60 min of ischemia. The onset of its peak value after ischemia was delayed in
      comparison to that of adenosine. Ischemia-evoked increases in xanthine
      concentration were attenuated by inhibition of adenosine deaminase or xanthine
      oxidase/xanthine dehydrogenase. Pre-ischemic inhibition of xanthine
      oxidase/xanthine dehydrogenase by oxypurinol (40 or 80 mg/kg intraperitoneally
      [IP]) resulted in a significant improvement in recovery of the a and b waves of
      the electroretinogram in comparison to a saline-treated control group.
      CONCLUSIONS: These results indicate that adenosine is a major component of the
      biochemical changes that occur after retinal ischemia. Long-lasting increases in
      xanthine concentration during reperfusion after ischemia could be a source of
      oxygen free radicals that may contribute to delayed injury of the retina,
      attempts to decrease xanthine concentration would ideally be initiated within one
      hour after the end of ischemia.

PMID- 9288449
TI  - Mediation of prostaglandin f2 alpha-induced ocular surface hyperemia by sensory
      nerves in rabbits.
AB  - PURPOSE: Prostaglandin F2 alpha (PGF2 alpha) and several other prostaglandins
      cause surface hyperemia of the eye when applied topically. The purpose of the
      present study was to investigate the role of sensory nerves in prostaglandin
      induced ocular hyperemia. METHODS: The ophthalmic branch of the trigeminal nerve
      was unilaterally electrocoagulated in rabbits using a stereotaxic technique. Two
      weeks later the animals received bilaterally one drop of PGF2 alpha-isopropyl
      ester (PGF2 alpha-IE) at a dose of 1 microgram/ eye. The blood flow to the
      different parts of the eye was measured with the radioactively labeled
      microsphere technique before, 30 and 60 min after treatment with PGF2 alpha-IE.
      RESULTS: In the control eyes with intact sensory innervation, PGF2 alpha-IE
      caused a marked increase in blood flow to the surface structures of the eye
      (conjunctiva, anterior sclera, eyelids and nictitating membrane) and the iris,
      and a moderate increase in the blood flow to the ciliary processes, but no
      increase in the choroidal blood flow. In the denervated eyes the increase in
      blood flow to the surface structures was almost completely abolished, and there
      was also a tendency toward less increase in blood flow in the anterior uvea.
      CONCLUSIONS: These results indicate that PGF2 alpha-induced ocular surface
      hyperemia, at least at the early stage, is mediated to a large extent by sensory
      nerves.

PMID- 9288450
TI  - Cell association increases RPE outgrowth from primary explant.
AB  - PURPOSE: Most studies of cell growth of the RPE employ cultures which have been
      previously passaged, but here we investigated freshly-explanted RPE cells, which
      may have been growth-quiescent for years, within the eye to determine whether co
      culture affects initial outgrowth in primary culture. METHODS: Bovine or human
      RPE were co-cultured in primary culture with several cell types to test the
      effects of homologous or heterologous cell association. For bovine RPE, cell
      number was measured over 14 days in cultures of RPE alone, or RPE in co-culture
      with irradiated living cells, with fixed-killed cells, with cells separated from
      the RPE by a semipermeable membrane, or in medium conditioned by the cell types
      used for co-culture. For human RPE, isolates from all donors were randomized,
      over a 13-month period, to co-culture or to culture alone. The number of cultures
      attaining a cell number at one month that was sufficient for further propagation
      was compared. RESULTS: Co-culture with irradiated living cells increased the
      growth of primary cultures of both bovine and human RPE. Living cells were
      required; fixed-killed cells were ineffective. The outgrowth-promoting activity
      was not tissue or species specific, and it appeared to require close cell
      association between the RPE and the co-culture cell population. Conditioned media
      were ineffective and rather were slightly growth inhibitory. Primary RPE cells
      showed an earlier expression of vimentin (a marker of Gzero-G1 transition), more
      rapid cell spreading, and a greater increase in cell number between 7 and 14 days
      after explant when grown in co-culture than when cultured alone. CONCLUSIONS: The
      results indicate that cell association between non-mitotic RPE cells and
      previously cultured cells of many types increases the outgrowth of the RPE by
      accelerating the early stages of growth activation in vitro. Co-culture methods
      offer a practical means for increasing the likelihood of producing cultures from
      small RPE isolates. Further, should cells involved in proliferative pathologies
      in situ associate with non-mitotic RPE within the monolayer, the latter cells may
      also be activated, leading to an augmentation of the pathology.

PMID- 9288451
TI  - Aqueous humor induces transforming growth factor-beta (TGF-beta)-producing
      regulatory T-cells.
AB  - PURPOSE: The intraocular microenvironment is an immune-privileged site where
      immunogenic inflammation is suppressed. Suppression of immunogenic inflammation
      has been associated with immunosuppressive factors found in aqueous humor
      produced by ocular tissues. To further understand the mechanisms suppressing
      immunogenic inflammation in the eye, we have examined the production of
      lymphokines by primed T-cells activated in the presence of aqueous humor.
      METHODS: Enriched in vivo primed T-cells were T-cell receptor-stimulated in the
      presence of fresh aqueous humor. The culture supernatant was assayed for IFN
      gamma and IL-4 by sandwich ELISA. TGF-beta production by T-cells stimulated in
      the presence of aqueous humor was assayed by a TGF-beta bioassay of the culture
      supernatant and by quantitative RT-PCR for TGF-beta 1 mRNA expression. Aqueous
      humor-treated T-cells were assayed for their capacity to suppress IFN-gamma
      production by stimulated, primed T-cells. RESULTS: Aqueous humor-enhanced
      proliferation but irreversibly suppressed production of both IFN-gamma and IL-4
      by in vitro-activated, in vivo-primed T-cells. Aqueous humor induced in vivo
      primed T-cells to produce TGF-beta in vitro, and these TGF-beta-producing T-cells
      suppressed IFN-gamma production by other T-cells activated in co-cultures.
      CONCLUSIONS: Aqueous humor alters the functional program of TCR-ligand-activated,
      primed T-cells, converting the cells to TGF-beta-producing regulatory cells.

PMID- 9288452
TI  - Role of T cells in the pathogenesis of autoimmune lacrimal gland disease in
      MRL/Mp-lpr/lpr mice.
AB  - PURPOSE: MRL/Mp-lpr/lpr mice (MRL/lpr) spontaneously develop an autoimmune
      disease, including lacrimal gland lesions, which are a model for Sjogren's
      syndrome. Target organ lesions in MRL/lpr mice are composed largely of CD4+ T
      cells, and treatment with monoclonal antibodies (mAb) against CD4 improves in the
      systemic autoimmune disease but not the lacrimal gland inflammation. In anti-CD4
      mAb-treated MRL/lpr mice, the lacrimal gland lesions are composed largely of CD8+
      T cells. The effects of depletion of: (1) all T cells; (2) both CD4+ and CD8+ T
      cells, and (3) only CD8+ T cells on the lacrimal gland disease were investigated.
      METHODS: MRL/lpr mice underwent neonatal thymectomy and were treated with weekly
      injections of 6 mg of anti-Thy 1 mAb from age one week until sacrifice at age
      five months. Control nonthymectomized mice underwent similar treatment with
      either saline or normal rat immunoglobulin (rIg) injections. In a second
      experiment, MRL/lpr mice were treated with weekly injections of either: (1) 2 mg
      anti-CD4 mAb and 5 mg anti-CD8; or (2) 5 mg anti-CD8 alone. Control mice
      underwent similar treatment with either saline or rIg injections. RESULTS:
      Combined treatment with neonatal thymectomy and anti-Thy 1 mAb was effective in
      reducing the lacrimal gland disease in both frequency (50% > or = grade 3 vs.
      100% in controls, P < 0.002) and extent (median 0% of lacrimal gland area
      involved by inflammation vs. 14.8% in controls; P = 0.01). Combined anti-CD4 and
      anti-CD8 therapy also was effective in reducing the lacrimal gland disease in
      terms of frequency (25% grade 3 vs. 93% in controls; P = 0.002) and extent
      (median 0% of lacrimal gland involved by inflammation vs. 12.9% in controls; P =
      0.0005). Treatment with anti-CD8 mAb therapy alone was ineffective. The systemic
      autoimmune disease was also improved by T cell depletion and by combined anti-CD4
      and anti-CD8 mAb therapy but not by anti-CD8 mAb therapy alone. CONCLUSIONS:
      Suppression of both CD4+ and CD8+ T cells is required to suppress lacrimal gland
      inflammation in MRL/lpr mice.

PMID- 9288453
TI  - On the nature of hereditary cataract in strain 13/N guinea pigs.
AB  - PURPOSE: Congenital nuclear cataracts in strain 13/N guinea pigs are caused by a
      single splice-site mutation in the zeta-crystallin gene. Very little is known of
      the physical factors involved in lens opacification of this system. The aim of
      this study is to elucidate the biophysical processes causing the nuclear
      turbidity. METHODS: Normal, homozygous and heterozygous mutant guinea pig lenses
      were studied. Polarized light scattering measurements were performed on thin
      sections of lenses as a function of scattering angle. Scattering intensities were
      collected in two modes, I- and I+. The total water content of lenses was
      determined by thermogravimetric analysis. The nonfreezable (bound) water content
      was obtained by differential scanning calorimetry. The morphology of lenses was
      investigated by scanning electron microscopy. RESULTS: Normal lenses scatter 5-
      to 10-fold less light than cataractous lenses at wide angles in both modes. The
      intensity ratios of the two modes imply that most of the scattering comes from
      density fluctuations; 10-20% of the turbidity may be contributed by orientation
      fluctuations. The nucleus of heterozygous cataractous lenses contain less total
      water than normal lenses, whereas the cortex has the same hydration as the normal
      lens. The nonfreezable water content of the cataractous nucleus is higher than
      that of the normal lens. Scanning electron microscopy showed frequent truncation
      of the fiber cells, cavitations and occasional longitudinal splitting resulting
      in hollow cylinder formation in the nucleus of the cataractous lens. CONCLUSION:
      Mutation of zeta-crystallin in guinea pigs causes a congenital cataract. A number
      of supramolecular events contribute to the turbidity. The mobile water leaves the
      nuclear fiber cells, causing a collapse of supramolecular structures. Both the
      size of the aggregates and their refractive index increase by this dehydration
      process, contributing to the turbidity. The truncation and hollowing of fiber
      cells causes the orientation fluctuations that also increase turbidity.

PMID- 9288454
TI  - Membrane type-1 matrix metalloproteinase in human ocular tissues.
AB  - PURPOSE: Membrane type-1 matrix metalloproteinase (MT1-MMP) (MMP-14) (EC
      3.4.24.xx) is involved in the activation of progelatinase A (MMP-2) (EC
      3.4.24.24). MMP-2 is present at least in the interphotoreceptor matrix and
      vitreous. The purpose of this study was to determine the distribution of MT1-MMP,
      and MMP-2, in human ocular tissues. METHODS: The distribution of MT1-MMP and MMP
      2 was investigated in vitreous and in membrane extracts from eye tissues obtained
      from postmortem human eyebank eyes. Western blot analysis was performed using
      mouse monoclonal anti-MT1-MMP and anti-MMP-2 antibodies. RESULTS: MT1-MMP was
      found in sclera, cornea, lens, choroid, retinal pigment epithelium (RPE) and
      retina. MMP-2 was found in sclera, cornea, choroid, vitreous, RPE and retina but
      was absent from lens. CONCLUSION: We provide the first evidence for the presence
      and distribution of membrane-type-1 matrix metalloproteinase in human ocular
      tissues. MT1-MMP may be responsible for the activation of progelatinase A in many
      ocular extracellular matrices in a manner similar to that exhibited in other
      systems.

PMID- 9288456
TI  - Mass spectroscopic identification of in vitro glycated sites of MIP.
AB  - PURPOSE: Earlier reconstitution studies showed that glycation of the major
      intrinsic peptide (MIP) of the lens affected the permeability of liposomes. This
      study is aimed to identify in vitro glycated sites. METHODS: Urea- and alkali
      washed calf lens membranes were incubated with 0 and 1 M glucose for 5 days.
      Following the incubation, MIP was purified by size exclusion HPLC. The C-terminus
      peptide of MIP was then cleaved by cyanogen bromide (CNBr) and purified by C4
      reversed-phase HPLC. The CNBr peptide was analyzed, either directly or after
      digestion with trypsin, by electrospray ionization mass spectrometry (ESIMS) and
      matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS).
      RESULTS: The ESIMS and MALDI-MS analyses of the intact C-terminus peptide from 1
      M glucose incubated samples showed a mass shift equivalent to one, two and three
      glucose adducts. The MALDI-MS of the tryptic digest of the same sample showed
      peptides with mass shift equivalent to one or more glucose adducts. Sequence
      assignment confirmed that these glycated peptides contained lys238 and lys259.
      Although the intact C-terminus peptide showed up to three glucose adducts, we
      could not assign any tryptic peptide that contained glycated lys228. Samples
      incubated with 0 M glucose did not show any protein modifications. CONCLUSIONS:
      The data suggest that in vitro glycation sites of calf lens MIP are lys238 and
      lys259, and possibly lys228.

PMID- 9288455
TI  - Biodegradable scleral implant for intravitreal controlled release of fluconazole.
AB  - PURPOSE: To evaluate the feasibility of using a biodegradable polymeric scleral
      implant containing fluconazole (FLCZ), a bis-triazole antifungal agent, as a
      potential intravitreal-controlled drug delivery system. METHODS: The scleral
      implants, loaded with 10, 20, 30, and 50% FLCZ, were prepared with biodegradable
      polymers of poly (DL-lactide-co-glycolide). Those with all loading doses were
      used for the in vitro release studies; those with 30% FLCZ were used for the
      intravitreal release studies in pigmented rabbits. The in vitro and in vivo
      release rates of FLCZ from the implants were measured periodically with
      spectrophotometry and high performance liquid chromatography, respectively. The
      effects of the implants on ocular tissues were evaluated ophthalmoscopically,
      histologically, and electrophysiologically. RESULTS: The scleral implants loaded
      with 10, 20, and 30% doses gradually released FLCZ over 4 weeks in vitro; those
      with 50% FLCZ released most of the drug in one week. FLCZ concentration in the
      rabbit vitreous remained within the 99% inhibitory concentration for Candida
      albicans for 3 weeks after implantation. The scleral implant gradually
      biodegraded, and it disappeared by 4 months after implantation. The
      electrophysiologic and histopathologic findings demonstrated no substantial toxic
      reactions in the ocular tissues. CONCLUSION: The current study suggests that a
      biodegradable, polymeric scleral implant containing FLCZ may be a promising
      intravitreal drug delivery system to treat fungal endophthalmitis.

PMID- 9288457
TI  - High-oxygen-transmissibility soft contact lenses do not induce limbal hyperaemia.
AB  - PURPOSE: To establish the temporal sequence of limbal hyperaemia in humans
      without contact-lens wear and during conventional and highly oxygen-permeable
      soft-contact-lens wear. METHODS: Two, 16-h, non-dispensing clinical studies were
      conducted, each incorporating 8 h of open eye with normal blinking, followed by 8
      h of eye closure during sleep. In the first study, six non-habitual contact-lens
      wearers did not wear contact lenses. In the second study, the same subjects were
      each randomly assigned, in a double-masked fashion, to wear a conventional, thin,
      38% water, pHEMA soft contact lens (SCL) in one eye and an experimental high Dk
      (EHD), 20%-water soft contact lens in the other. Limbal redness (LR) was graded,
      using a 0-4 scale with decimalised subdivisions, at baseline and after 4, 8 and
      16 h. ANOVA was applied to the data, and the level for statistical significance
      was set at p < or = 0.005. RESULTS: In the non-wearing eye, LR changes averaged
      0.2 +/- 0.2 and 0.4 +/- 0.2 grades at 4 and 16 h, respectively (inferior
      quadrant). The corresponding values for SCL wear were 1.0 +/- 0.6 and 1.1 +/-
      0.6, while for EHD wear they were 0.2 +/- 0.4 and 0.5 +/- 0.5. Both for the
      normal eye and those wearing EHD lenses, increases in LR were significant only
      during eye closure (p < 0.005). During SCL wear, significant and larger LR
      increases were seen after 4 h open eye wear (p < 0.005), with only relatively
      small further changes being observed over the next 12 h. CONCLUSIONS: SCL wear
      induces a marked increase in limbal hyperaemia during open-eye wear, which is not
      seen either in the no lens situation or when EHD lenses are worn. The pattern of
      limbal hyperaemia for both the open and closed eyes during EHD lens wear is very
      similar to that for the no-lens situation. The mechanism whereby SCL induces
      excess limbal hyperaemia has not been absolutely established, but it may involve
      local hypoxia.

PMID- 9288458
TI  - Evaluation of recombinant adeno-associated virus as a gene transfer vector for
      the retina.
AB  - PURPOSE: To evaluate recombinant adeno-associated virus (AAV) as an in vivo gene
      transfer vector for the retina. METHODS: A recombinant AAV, vCMVp-lacZ, in which
      the bacterial beta-galactosidase reporter gene (lacZ) was placed under the
      control of a cytomegalovirus (CMV) early promoter, was injected into the vitreous
      body or the subretinal space of mouse eyes. The reporter gene expression was
      followed by histochemical analyses from 10 to 100 days post-injection. The effect
      of several variables on the extent of AAV-mediated gene transfer was examined,
      including routes of delivery, presence of an underlying mutation that caused
      retinal degeneration, and prior treatment with hydroxyurea. RESULTS: As measured
      by reporter gene expression, the AAV vector mediated gene transfer to three major
      cell types in the retina: the retinal pigment epithelium (RPE), ganglion cells
      and photoreceptor cells. Following a single injection, more than half of the
      total retinal areas were typically positive for gene transfer. Reporter gene
      expression was stable for at least 3 months, the farthest time point examined.
      Gene transfer to photoreceptor cells was observed only following subretinal
      delivery, and was greatly enhanced in mice undergoing early retinal degeneration.
      Cells in the inner nuclear layer were rarely transduced. Systemic administration
      of a genotoxic drug, hydroxyurea, 2 days prior to AAV delivery did not affect the
      patterns and extent of reporter gene expression. There was minimal histopathology
      associated with AAV transduction in the retinas of recipient mice, as determined
      by light microscopy. CONCLUSION: Recombinant AAV mediates efficient gene transfer
      to RPE and ganglion cells, and to photoreceptor cells under certain conditions.
      Persistence of transgene expression is of long duration and without apparent
      histopathology. The greater stability, lower cytopathicity, and the ability to
      transduce retinal ganglion cells are three distinct features of the AAV vector
      compared to current adenovirus-based vectors.

PMID- 9288459
TI  - Presence of ERK2 in rat retinal cells.
AB  - PURPOSE: Extracellular signal-regulated kinase 2 (ERK2) participates in the
      phosphorylation cascade that is activated in the an early intracellular response
      to various hormones and growth factors. We examined the expression and
      distribution of the ERK2 protein and mRNA in the rat retina before and after
      light exposure. METHODS: Rats were held on a 12 hr light/dark cycle and their
      retinas were removed and examined either just before or 2 or 30 min after light
      exposure. The tissue was processed for Western blotting to evaluate the presence
      of the protein for ERK2, and for in situ hybridization to evaluate the mRNA of
      ERK2. RESULTS: The Western blotting method showed a strong specific staining of a
      42 kDa protein band in the retinal samples. This band corresponded to the
      expected size of p42 MAP kinase (ERK2). In situ hybridization histochemistry
      showed an intense localization of ERK2 mRNA in the outer nuclear layer (ONL), the
      inner nuclear layer (INL), and the ganglion cell layer (GCL) of the retina. The
      intensity and distribution of these signals did not differ among the animals,
      regardless of exposure to light. CONCLUSIONS: While ERK2 may be involved in the
      signal transduction system activated in retinal cells by light exposure, its
      precise role remains to be defined.

PMID- 9288460
TI  - Detection of substance P in human tears by laser desorption mass spectrometry and
      immunoassay.
AB  - PURPOSE: To determine whether substance P is present in human tears. METHODS:
      Tear samples (1-2 microliters) were collected from one eye of each of 12
      subjects. Two of the eyes had dry eye syndrome, two wore contact lenses and had
      dry eye syndrome, and eight were normal. Five of the eight normal eyes were
      scheduled to undergo excimer laser refractive surgery, and tears were collected
      from these eyes before and after surgery. Tear samples were analyzed by laser
      desorption mass spectrometry. Pooled samples from one individual were subjected
      to enzyme-linked immunoabsorbent assay. RESULTS: Laser desorption mass spectra of
      the 18 tear samples displayed well defined peaks with mass to charge (m/z) ratios
      ranging from 1343.7 to 1355.9 and/or 1356.9 to 1364.7, corresponding to an
      average m/z of 1349.8 +/- 1.13 for protonated substance P and 1361.2 +/- 0.54 for
      oxidized substance P obtained from 14 mass spectra of standards formulated with
      substance P concentrations ranging from 10(-4) M to 10(-12) M. As confirmation,
      an enzyme-linked immunoabsorbent assay performed twice on pooled tears from one
      eye detected substance P in both replicates at a concentration of 125 pg/ml (9.26
      x 10(-11) M). CONCLUSIONS: These findings demonstrate that substance P is a
      component of tears obtained from normal eyes of men and women ranging in age from
      26 to 60 years, from eyes fitted with contact lenses, from eyes with dry eye
      syndrome, and from eyes 1 and 2 days after excimer laser refractive surgery.
      Whether the concentration of substance P in tears varies with sex, age, or eye
      condition, the source of substance P in tears, and its role in tears remains to
      be discovered.

PMID- 9288461
TI  - Inhibitors of the platelet GP IIb-IIIa function in the treatment of acute
      coronary syndromes.
AB  - Platelet activation is a critical mechanism in acute coronary artery syndromes
      and ischemic complications of percutaneous coronary revascularization. Thrombin
      and platelet inhibition are the current mainstays of therapy for these problems.
      Inhibitors of platelet GP IIb-IIIa, the final common pathway of platelet
      aggregation, have recently undergone clinical evaluation as therapeutics for
      acute ischemic syndromes, and as adjuvants for percutaneous revascularization.
      The results of these prospective, controlled trials, and current evaluations of
      GP IIb-IIIa inhibitors are summarized in this review.

PMID- 9288462
TI  - Venous thromboembolism in the cancer patient.
AB  - Patients with malignancies are at increased risk of developing venous
      thromboembolic disease. Diagnosis and treatment of deep venous thromboembolism
      and pulmonary embolism in this group of patients poses some unique challenges,
      but generally should parallel that of patients without malignancy. Prophylaxis
      with low-dose warfarin should be considered in patients with indwelling central
      venous catheters and in some patients receiving chemotherapy for cancer. Although
      patients who present with idiopathic deep venous thromboembolism or pulmonary
      embolism may be at increased risk of developing clinically apparent malignancy,
      there is no data to suggest that an aggressive search for cancer in these
      patients is more appropriate than routine physical exam and laboratory testing.

PMID- 9288463
TI  - Mechanism of action and clinical trials of Mpl ligand.
AB  - Mpl ligand is the hematopoietic growth factor responsible for regulating the
      production of platelets. Since its discovery just 3 years ago, it has provided
      both unique insights into megakaryocytopoiesis and the means to stimulate
      platelet production in numerous clinical situations. In animals deficient in Mpl
      ligand, the number of megakaryocytes and platelets decreases by more than 80%. In
      addition to having an effect on the megakaryocyte lineage, Mpl ligand supports
      the growth of stem cells, multipotential cells, and erythroid precursors. The
      endogenous Mpl ligand, thrombopoietin, is produced in the liver and kidneys, and
      circulating levels appear to be regulated primarily by the mass of platelets and
      megakaryocytes, which bind and catabolize Mpl ligand. The clinical utility of
      recombinant Mpl ligands is currently under intense investigation. Early results
      have demonstrated a marked stimulation of megakaryocyte and platelet production
      with no apparent adverse effects. In patients with cancer who are treated with
      chemotherapy, the duration of thrombocytopenia was shorter in patients treated
      with Mpl ligand than in those receiving placebo. The eventual role of Mpl ligand
      in clinical practice will be determined by the results of many ongoing clinical
      studies.

PMID- 9288464
TI  - Structure and function of platelet alpha IIb beta 3.
AB  - Platelet aggregation is mediated by the platelet fibrinogen receptor, the alpha
      IIb beta 3 integrin (glycoprotein IIb-IIIa). This integrin has served as a
      prototype for studies probing structure-function relationships, cellular
      modulation of integrin function, and integrin-mediated signaling. Use of new
      model systems and molecular approaches have helped investigators to make rapid
      progress in our understanding of these areas, as reviewed here.

PMID- 9288465
TI  - Structure and function of the glycoprotein Ib-IX-V complex.
AB  - Following injury to a blood vessel, platelets rapidly adhere to the site of
      exposed subendothelial matrix in the vessel wall, become activated, and secrete
      granule contents that will recruit and activate other platelets, which then
      aggregate at the site and seal the defect in the vessel wall. The clot that forms
      prevents further blood loss. This process can become deranged in diseased blood
      vessels, such as coronary arteries narrowed by atherosclerosis. Platelets will
      also adhere to these vessels when matrix components are exposed by plaque
      rupture, with potentially disastrous results. The platelet glycoprotein Ib-IX-V
      complex plays crucial roles in both of these processes by mediating platelet
      adhesion to sites of blood vessel injury and by participating in the thrombin
      induced aggregation of platelets. This adhesion receptor complex is unique in
      that it is the only one of its kind. In this review, we discuss recent
      developments in elucidating the structure, topography, and functions of this
      important receptor complex.

PMID- 9288466
TI  - Platelet kinetics.
AB  - Platelet survival can be determined with considerable precision using
      radioisotopic methodologies; however, complications associated with these
      techniques still catalyze the search for nonisotopic procedures to estimate
      platelet survival as well as surrogate markers of platelet life span. Recent
      reports on markers of platelet age have focused on thiazole orange-staining for
      enumeration of "reticulated platelets," ie, young platelets with residual mRNA.
      Numerous clinical studies have observed a correlation between thiazole orange
      positive platelets and platelet synthesis, thereby providing a noninvasive means
      to differentiate between synthetic and destructive mechanisms in
      thrombocytopenia. Additionally, nonisotopic methods for quantitating platelet
      survival have recently been developed in animal systems, although they have not
      yet been transferred to human use. And finally, an ancillary topic related to
      platelet turnover is the impact of cell age on platelet reactivity. Prevailing
      paradigms concerning age and reactivity are complicated by recent studies with
      cytokines, such as interleukin-6, which demonstrate that platelet age is not the
      sole determinant of platelet reactivity.

PMID- 9288467
TI  - Thrombosis in pregnancy.
AB  - Thrombosis during pregnancy poses special problems. This review focuses on risk
      factors for the development of venous thromboembolism during pregnancy, diagnosis
      of deep vein thrombosis and pulmonary embolism during pregnancy, therapeutic
      recommendations for the treatment of acute thromboembolism during pregnancy, and
      thromboprophylaxis in the pregnant woman. Management of pregnant women with
      antiphospholipid antibodies is also reviewed.

PMID- 9288468
TI  - Mechanisms of activity of lupus anticoagulants.
AB  - Lupus anticoagulants comprise a heterogenous group of circulating immunoglobulins
      that are associated with an increased risk of thrombosis. It was believed earlier
      that these antibodies were directed against anionic phospholipids. Recent
      findings, however, establish that the autoantibodies in lupus anticoagulants are
      not directed against "native" anionic phospholipids but rather to modified
      phospholipids, lipid-protein adducts, and certain phospholipid binding proteins.
      Despite a marked increase in the number of citations in recent years on
      laboratory and clinical manifestations of lupus anticoagulants, the pathogenetic
      mechanisms involved remain unknown. This review focuses on antigen specificities
      of autoantibodies in lupus anticoagulants and the mechanisms by which these
      antibodies contribute to an increased thrombotic risk in patients with lupus
      anticoagulant.

PMID- 9288469
TI  - Polyphosphoinositide synthesis and platelet shape change.
AB  - Polyphosphoinositides both integrate signaling pathways at the cytoplasmic
      surface of the plasma membrane and serve as the final messenger of signaling
      pathways. They have a well-defined role in the release of calcium through the
      degradative pathway. Recent work, however, has highlighted the role of the
      polyphosphoinositide synthetic pathways in activated cells. This review
      emphasizes the role of polyphosphoinositides in recruiting signaling proteins
      that have pleckstrin homology domains and in directly regulating actin assembly
      in the human blood platelet.

PMID- 9288471
TI  - Hemostasis and thrombosis.

PMID- 9288470
TI  - Congenital dysfibrinogenemia.
AB  - Fibrinogen abnormalities can be classified as congenital or acquired. Each class
      manifests quantitative or qualitative alterations; the latter are known as
      dysfibrinogenemias. In dysfibrinogenemias, structural defects cause alterations
      in the conversion of fibrinogen to fibrin. Approximately 300 abnormal fibrinogens
      have been reported, and about 83 structural defects have been identified. The
      most common structural defect involve the fibrinopeptides and their cleavage
      sites, and the second most common involves the gamma-chain polymerization region.
      Approximately half of the mutants are clinically silent, whereas hemorrhage and
      thrombosis occur in almost equal numbers of cases. Study of the abnormal
      fibrinogens has provided insight into fibrinogen structure and fibrin formation
      and dissolution. Some of the structural abnormalities exhibit defective assembly
      and activation of components of the fibrinolytic system on the abnormal fibrin,
      resulting in impaired dissolution of fibrin, clinically associated with
      thrombosis.

PMID- 9288473
TI  - A new method of measuring distortion product otoacoustic emissions using multiple
      tone pairs: study of human adults.
AB  - OBJECTIVE: To increase the speed of a distortion product otoacoustic emissions
      (DPOE) test of cochlear function by employing a new multiple-tone-pair method and
      to validate the method. DESIGN: We used a new method of employing multiple tone
      pairs in measuring DPOEs proposed by Zurek and Rabinowitz and implemented in a
      modified Grason-Stadler Model GSI-60. We investigated the applicability of the
      multiple-pair method by comparing the 2f1-f2 DPOEs obtained with a 3-pair method
      with the conventional 1-pair results in human adults; f1 and f2 represent two
      frequencies of each tone pair, f1 < f2, f2/f1 = 1.2. We used two sets of 3-pair
      stimuli: 1) f2 at 1.5, 3, and 6 kHz; and 2) f2 at 2, 4, and 8 kHz. The 1-pair
      stimuli had f2 at each of the above six frequencies. The primary tone levels were
      L1 = 65 and L2 = 50 dB SPL re 20 microPa. RESULTS: We obtained DPOEs from 98 ears
      with normal hearing and 94 ears with sensorineural hearing loss in 103 human
      adults. We found: 1) that the DPOE levels obtained with the 3-pair method were
      strongly correlated with those of the 1-pair method, with correlation
      coefficients of 0.83 to 0.96; 2) that the mean DPOE level versus frequency
      functions for the normal ears were similar between the 3-pair and 1-pair methods;
      a 2-way analysis of variance indicated no significant difference between the two
      methods; 3) that the mean difference between DPOE levels obtained with the 3-pair
      and 1-pair methods was small (less than 1.3 dB in 11 of the 12 conditions
      examined, i.e., six frequencies each for normal ears and hearing-impaired ears)
      although the differences were significant in 6 of the 12 conditions as determined
      by the paired t-test; and 4) that the DPOE test performances of distinguishing
      normal from impaired ears were similar between the 3-pair and 1-pair tests; areas
      under the receiver operating characteristic curves were not significantly
      different between the two tests for four of the six frequencies tested as
      determined by a statistical procedure of Hanley and McNeil; for the remaining two
      frequencies where the differences were significant, each of the two tests was
      better than the other at one frequency. CONCLUSIONS: The 3-pair DPOE method
      yielded results generally in good agreement with those of the conventional 1-pair
      DPOE method. To our knowledge, this is the first systematic study of a multiple
      pair DPOE method. Because a 3-pair method can be conducted approximately two to
      three times as fast as a 1-pair method, the former is advantageous, particularly
      for an auditory screening test.

PMID- 9288472
TI  - Field sensitivity of targeted neonatal hearing screening by transient-evoked
      otoacoustic emissions.
AB  - OBJECTIVE: Population ascertainment of children having bilateral moderate to
      profound hearing impairment was undertaken to find out how many had passed (false
      negatives) and how many had failed (true negatives) a neonatal screening test
      based on transient-evoked otoacoustic emissions (TEOAE). DESIGN: Neonatal
      screening using a purpose-built TEOAE instrument was undertaken in neonates, at
      eight hospitals in districts distributed around the United Kingdom starting in
      1988. Screening was targeted on neonates at risk of hearing impairment. A total
      of 7500 babies had been tested by the end of 1995. Searching of audiological
      records in the districts completed at the end of 1995 ascertained 218 children
      born between January 1988 and December 1993 who 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 those, 47 had completed the neonatal TEOAE screening test. Retrospective
      examination of their TEOAE records indicated whether they had passed or failed
      the screening test. RESULTS: Eleven of the 47 had passed the screening test,
      although two of those had documented acquired hearing impairment occurring after
      screening. Disregarding those two cases leaves nine false negatives out of 45,
      giving a sensitivity estimate of 80% (36 divided by 45). In two of the nine
      cases, there was documented evidence of progression, one of whom had a family
      history of progressive hearing loss. CONCLUSIONS: Targeted neonatal hearing
      screening programs based on TEOAE can expect to identify hearing impairment in
      approximately 80% of babies screened. The cause of false negatives is a matter
      for conjecture. There may be several reasons: the test may give an incorrect
      result, there may be a later acquired hearing impairment, or there may be a
      progressive hearing loss of unknown origin. Passing a neonatal screening test is
      not a valid reason to forego further surveillance, or to disregard parental
      suspicion of hearing impairment.

PMID- 9288474
TI  - The role of transient-evoked otoacoustic emission testing in the evaluation of
      elderly persons.
AB  - OBJECTIVE: The purposes of this study were: To determine the quantitative and
      qualitative changes that occur in transient-evoked otoacoustic emissions (TEOAEs)
      in older individuals without addressing the effect of aging alone and without
      correction for hearing loss of the subject selection. To investigate the clinical
      value of measuring TEOAEs in the routine audiological evaluation of older people
      reasoning that a finding of hearing loss in the presence of TEOAEs could indicate
      a form of presbycusis with a primary central component. DESIGN: Click-evoked
      otoacoustic emissions (CEOAEs) were measured in 201 subjects without middle ear
      problems aged 60 yr and older (range 60 to 97 yr) who volunteered for the study
      because of complaints concerning their hearing. Audiological procedures included
      a pure-tone audiogram, modified Speech Perception in Noise test (German version:
      Basler Satztest), and the Hearing Handicap Inventory for the Elderly (German
      version). Results from ears with a pure-tone average (PTA) at 0.5, 1, and 2 kHz
      of < or = 30 dB HL were further analyzed with respect to the presence or absence
      of CEOAEs. In addition, tone burst evoked otoacoustic emissions (TbOAEs) were
      tested in ears with responses to click stimuli. The test consisted of a paradigm
      used previously in our laboratory to assess superposition and suppression of
      frequency within the cochlea (see Xu, Probst, Harris, & Roede, 1994). RESULTS:
      CEOAEs were not detectable in ears with a PTA > 30 dB HL. The prevalence of
      CEOAEs in ears with a PTA < or = 30 dB HL was 60%. Response levels decreased as
      hearing thresholds became poorer, but there was no apparent influence on TEOAE
      level due to age alone. The audiological measures from ears with and without
      CEOAEs and with PTAs < or = 30 dB HL were similar with the exception of small
      between group differences at lower frequencies. The TbOAE results showed no
      differences in linear superposition and suppression when results were compared
      with those of younger subjects tested previously. CONCLUSIONS: The lower overall
      amplitudes of TEOAEs and the lower prevalence of 60% in comparison to results
      from younger subjects with normal hearing imply that cochlear changes do occur
      with aging. However, the preservation or loss of TEOAEs does not separate
      subjects with presbycusis into distinct audiological categories or handicaps.
      Tone burst results suggest that frequency processing within the cochlea is not
      affected by age alone. We conclude that TEOAEs add no relevant information in the
      routine clinical evaluation of elderly persons with hearing problems.

PMID- 9288475
TI  - Subjective judgments of speech clarity measured by paired comparisons and
      category rating.
AB  - OBJECTIVE: The purpose of this study was to compare listeners' subjective
      judgments of speech clarity via paired comparisons and category rating using
      stimulus conditions that varied in the relative spacing between stimulus items,
      producing either a wide or narrow range of performance. DESIGN: Subjective
      judgments of speech clarity were measured via paired comparisons and category
      rating in 12 normal-hearing (Experiment 1) and eight hearing-impaired adults
      (Experiment 2). Sentences processed by six band-pass filters that increased
      monotonically in Articulation Index (AI) estimates constituted the stimuli to be
      judged. Using subsets of three filters from the group of six, subjective
      judgments were additionally obtained for stimulus conditions in which the
      performance ranges were wide (large differences in AI) and narrow (small
      differences in AI). RESULTS: Speech clarity judgments obtained by paired
      comparisons and category rating were highly related to the AI estimates both for
      normal-hearing and hearing-impaired subjects. When the performance range was
      wide, both methods provided similar judgments for the normal-hearing subjects.
      For the hearing-impaired subjects, paired comparisons were more sensitive than
      category rating. When the performance range was narrow, paired comparisons were
      more sensitive than category rating in differentiating between filters for both
      groups of subjects. This difference was less obvious for the normal-hearing
      subjects when paired comparison data were converted to a scale comparable to the
      category ratings. Large between-subject variability was evident for the hearing
      impaired subjects on the psychophysical scaling procedures, most notably for
      category rating. CONCLUSIONS: When judging the clarity among stimulus items where
      performance varied over a wide range, both category rating and paired comparisons
      provided comparable judgments for normal-hearing listeners. For conditions in
      which perceptual differences between stimulus items were restricted either by the
      choice of conditions or by the effects of sensorineural hearing loss, the method
      of paired comparisons was the more sensitive procedure.

PMID- 9288476
TI  - A comparison of vowel production by children with multichannel cochlear implants
      or tactile aids: perceptual evidence.
AB  - OBJECTIVE: To examine changes in perceived vowel production accuracy over time in
      prelingually deafened children who use a multichannel cochlear implant (Nucleus
      22 channel) or a multichannel tactile aid (Tactaid 7) and to compare the levels
      of perceived vowel production accuracy attained by the two device groups. DESIGN:
      The subjects were participants in longitudinal studies of the effects of sensory
      aids on the development of perceptual, speech, and language skills. As part of
      these studies, imitative vowel productions were elicited and transcribed before
      each child received their sensory aid and at 6 mo intervals thereafter. Data for
      the current study was obtained from the predevice interval and a later interval
      (postdevice) that was an average of 1.8 yr after the subjects received their
      respective devices. The subjects' vowel productions were judged for accuracy in
      matching an imitative model and for correctness of vowel features (height and
      place). Within-group analyses were completed to determine if vowel production
      scores improved over the course of the study for each device group. Between group
      comparisons were performed to examine differences in mean scores at each
      interval. RESULTS: Before receiving their multichannel devices, the two groups of
      subjects demonstrated similar imitative vowel production skills. After an average
      of 1.8 yr of device use, the cochlear implant subjects demonstrated significantly
      improved production of diphthongs and all vowel categories except low vowels. The
      Tactaid 7 subjects demonstrated significant improvement only in the production of
      diphthongs. Thus, cochlear implant recipients' vowel production skills were found
      to be significantly better than those of the Tactaid 7 users after a comparable
      amount of device experience. CONCLUSIONS: The vowel production gains of the
      cochlear implant subjects were similar in amount to those noted in other studies
      of children who use the Nucleus multichannel cochlear implant and further confirm
      the potential of this device for improved speech production in prelingually
      deafened children. The differences between the performance of the two groups
      demonstrate that vowel production skills improved to a greater degree through use
      of a multichannel cochlear implant than through use of the Tactaid 7.

PMID- 9288478
TI  - Standard and multifrequency tympanometry in normal and otosclerotic ears.
AB  - OBJECTIVES: The primary goal of this study was to evaluate alternative
      tympanometric parameters for distinguishing normal middle ears from ears with
      otosclerosis. A secondary goal was to provide guidelines and normative data for
      interpreting multifrequency tympanometry obtained using the Virtual 310
      immittance system. DESIGN: Nine tympanometric measures were examined in 68 normal
      ears and 14 ears with surgically confirmed otosclerosis. No subjects in either
      group had a history of head trauma or otoscopic evidence of eardrum
      abnormalities. Two parameters, static admittance and tympanometric width, were
      derived from standard low-frequency tympanometry and two parameters, resonant
      frequency and frequency corresponding to admittance phase angle of 45 degrees
      (F45 degrees), were derived from multifrequency tympanometry. RESULTS:
      Differences between normal and otosclerotic ears were statistically significant
      only for resonant frequency and F45 degrees. Group differences in resonant
      frequency were larger when estimated using positive tail, rather than negative
      tail, compensation. Group differences in both resonant frequency and F45 degrees
      were larger when estimated from sweep frequency (SF), rather than sweep pressure,
      tympanograms. Test performance analysis and patterns of individual test
      performance point to two independent signs of otosclerosis in the patient group;
      1) an increase in the stiffness of the middle ear, best indexed by F45 degrees
      derived from SF recordings, and 2) a change in the dynamic response of the
      tympanic membrane/middle ear system to changes in ear canal pressure, best
      indexed by tympanometric width. Most patients were correctly identified by only
      one of these two signs. Thus, optimal test performance was achieved by combining
      F45 degrees derived from SF recordings and tympanometric width. CONCLUSIONS: The
      findings confirm the advantage of multifrequency tympanometry over standard low
      frequency tympanometry in differentiating otosclerotic and normal ears.
      Recommendations for interpreting resonant frequency and F45 degrees measures
      obtained using the Virtual Immittance system are also provided. In addition, the
      relationship among different tympanometric measures suggests a general strategy
      for combining tympanometric measures to improve the identification of
      otosclerosis.

PMID- 9288477
TI  - Pulse rate matching by cochlear implant patients: effects of loudness
      randomization and electrode position.
AB  - OBJECTIVE: To assess the accuracy with which cochlear implant patients are able
      to match two stimuli on the basis of pulse rate pitch. DESIGN: Patients were
      required to adjust the pulse rate of a comparison stimulus to match that of a
      fixed reference stimulus. The comparison and the reference stimuli differed in
      loudness or were presented to different electrodes. RESULTS: Patients were able
      to match stimuli on the basis of pulse rate, with varying degrees of accuracy.
      Deviations from the target and the amount of variability were greater when
      stimuli were presented to different electrodes. The results also provide evidence
      regarding level-dependent pitch shifts. CONCLUSIONS: Because of methodological
      limitations, conclusions regarding pitch equivalence are limited. However,
      patients vary significantly in their ability to utilize temporal information.

PMID- 9288479
TI  - Field-to-microphone transfer functions for completely-in-the-canal (CIC)
      instruments.
AB  - OBJECTIVE: To measure the field-to-microphone transfer function for two sizes of
      completely-in-the-canal (CIC) devices, at two loudspeaker azimuths. DESIGN: Field
      to-microphone transfer functions were measured for both standard- and micro-CIC
      instruments, at 0 degree and 45 degrees azimuth, in a sample of 24 adults. This
      was accomplished with custom instruments, which allowed for a direct connection
      between the CIC microphone electrical output and the measurement/analysis
      instrumentation system. RESULTS: For the standard-CIC, the peak in the average
      field-to-microphone transfer function was 8 dB at 4000 Hz for 0 degree azimuth
      and 13.7 dB at 5000 Hz for 45 degrees azimuth. CONCLUSIONS: The results
      demonstrate and define, at two signal azimuths, the acoustic advantage of the CIC
      microphone placement relative to that reported for alternative hearing aid
      styles.

PMID- 9288480
TI  - Converting insertion gain to and from headphone coupler responses.
AB  - OBJECTIVE: The paper aims to show how insertion gain responses can be translated
      into equivalent headphone responses, and vice versa. DESIGN: The relationship
      between the response types is theoretically derived by allowing for real ear to
      coupler differences and for real ear unaided responses. RESULTS: The necessary
      corrections for each of these factors are obtained from published data, and the
      combined correction factors are compared with independently obtained published
      data. CONCLUSIONS: The equations and data presented can be used to translate
      insertion gain responses into responses suitable for use with equipment using
      headphones and, by inference, insert phones.

PMID- 9288481
TI  - Playing in the sand.

PMID- 9288482
TI  - Radiation exposure and cancer: a simpler view of Three Mile Island.

PMID- 9288483
TI  - Consequences of the 1979 Three Mile Island accident continued: further comment.

PMID- 9288484
TI  - Bisphenol A in food cans: an update.

PMID- 9288485
TI  - NRDC report trashes recycling critics.

PMID- 9288486
TI  - Environmental aces.

PMID- 9288487
TI  - Fake DNA.

PMID- 9288488
TI  - A known human carcinogen.

PMID- 9288489
TI  - Understanding gene-environment interactions.

PMID- 9288490
TI  - NIEHS director receives inaugural NAPE Award.

PMID- 9288491
TI  - A driving force.

PMID- 9288492
TI  - Exotic invasion.

PMID- 9288493
TI  - Mapping the environment.

PMID- 9288494
TI  - Geographic information systems: their use in environmental epidemiologic
      research.
AB  - Advances in geographic information system (GIS) technology, developed by
      geographers, provide new opportunities for environmental epidemiologists to study
      associations between environmental exposures and the spatial distribution of
      disease. A GIS is a powerful computer mapping and analysis technology capable of
      integrating large quantities of geographic (spatial) data as well as linking
      geographic with nongeographic data (e.g., demographic information, environmental
      exposure levels). In this paper we provide an overview of some of the
      capabilities and limitations of GIS technology; we illustrate, through practical
      examples, the use of several functions of a GIS including automated address
      matching, distance functions, buffer analysis, spatial query, and polygon
      overlay; we discuss methods and limitations of address geocoding, often central
      to the use of a GIS in environmental epidemiologic research; and we suggest ways
      to facilitate its use in future studies. Collaborative efforts between
      epidemiologists, biostatisticians, environmental scientists, GIS specialists, and
      medical geographers are needed to realize the full potential of GIS technology in
      environmental health research and may lead to innovative solutions to complex
      questions.

PMID- 9288495
TI  - The relationship between selected causes of postneonatal infant mortality and
      particulate air pollution in the United States.
AB  - Recent studies have found associations between particulate air pollution and
      total and adult mortality. The relationship between particulate air pollution and
      mortality among infants has not been examined in the United States. This study
      evaluates the relationship between postneonatal infant mortality and particulate
      matter in the United States. Our study involved analysis of cohorts consisting of
      approximately 4 million infants born between 1989 and 1991 in states that report
      relevant covariates; this included 86 metropolitan statistical areas (MSAs) in
      the United States. Data from the National Center for Health Statistics-linked
      birth/infant death records were combined at the MSA level with measurements of
      particulate matter 10 microns or less (PM10) from the EPA's Aerometric Database.
      Infants were categorized as having high, medium, or low exposures based on
      tertiles of PM10. Total and cause-specific postneonatal mortality rates were
      examined using logistic regression to control for demographic and environmental
      factors. Overall postneonatal mortality rates were 3.1 among infants with low
      PM10 exposures, 3.5 among infants with medium PM10 exposures, and 3.7 among
      highly exposed infants. After adjustment for other covariates, the odds ratio
      (OR) and 95% confidence intervals (CI) for total postneonatal mortality for the
      high exposure versus the low exposure group was 1.10 (1.04, 1.16). In normal
      birth weight infants, high PM10 exposure was associated with respiratory causes
      [OR = 1.40, (1.05, 1.85)] and sudden infant death syndrome [OR = 1.26, (1.14,
      1.39)]. For low birth weight babies, high PM10 exposure was associated, but not
      significantly, with mortality from respiratory causes [OR = 1.18, (0.86, 1.61)].
      This study suggests that particulate matter is associated with risk of
      postneonatal mortality. Continued attention should be paid to air quality to
      ensure optimal health of infants in the United States.

PMID- 9288496
TI  - The role of particulate size and chemistry in the association between summertime
      ambient air pollution and hospitalization for cardiorespiratory diseases.
AB  - In order to address the role that the ambient air pollution mix, comprised of
      gaseous pollutants and various physical and chemical measures of particulate
      matter, plays in exacerbating cardiorespiratory disease, daily measures of fine
      and coarse particulate mass, aerosol chemistry (sulfates and acidity), and
      gaseous pollution (ozone, nitrogen dioxide, sulfur dioxide, and carbon monoxide)
      were collected in Toronto, Ontario, Canada, in the summers of 1992, 1993, and
      1994. These time series were then compared with concurrent data on the number of
      daily admissions to hospitals for either cardiac diseases (ischemic heart
      disease, heart failure, and dysthymias) or respiratory diseases
      (tracheobronchitis, chronic obstructive long disease, asthma, and pneumonia).
      After adjusting the admission time series for long-term temporal trends, seasonal
      variations, the effects of short-term epidemics, day of the week effects, and
      ambient temperature and dew point temperature, positive associations were
      observed for all ambient air pollutants for both respiratory and cardiac
      diseases. Ozone was least sensitive to adjustment for the gaseous and particulate
      pollution measures. However, the association between the health outcomes and
      carbon monoxide, fine and coarse mass, sulfate levels and aerosol acidity could
      be explained by adjustment for exposure to gaseous pollutants. Increases in
      ozone, nitrogen dioxide, and sulfur dioxide equivalent to their interquartile
      ranges corresponded to an 11% and 13% increase in daily hospitalizations for
      respiratory and cardiac diseases, respectively. The inclusion of any one of the
      particulate air pollutants in multiple regression models did not increase these
      percentages. Particle mass and chemistry could not be identified as an
      independent risk factor for the exacerbation of cardiorespiratory diseases in
      this study beyond that attributable to climate and gaseous air pollution. We
      recommend that effects of particulate matter on health be assessed in conjunction
      with temporally covarying gaseous air pollutants.

PMID- 9288498
TI  - Alveolar breath sampling and analysis to assess trihalomethane exposures during
      competitive swimming training.
AB  - Alveolar breath sampling was used to assess trihalomethane (THM) exposures
      encountered by collegiate swimmers during a typical 2-hr training period in an
      indoor natatorium. The breath samples were collected at regular intervals before,
      during, and for 3 hr after a moderately intense training workout. Integrated and
      grab whole-air samples were collected during the training period to help
      determine inhalation exposures, and pool water samples were collected to help
      assess dermal exposures. Resulting breath samples collected during the workout
      demonstrated a rapid uptake of two THMs (chloroform and bromodichloromethane),
      with chloroform concentrations exceeding the natatorium air levels within 8 min
      after the exposure began. Chloroform levels continued to rise steeply until they
      were more than two times the indoor levels, providing evidence that the dermal
      route of exposure was relatively rapid and ultimately more important than the
      inhalation route in this training scenario. Chloroform elimination after the
      exposure period was fitted to a three compartment model that allowed estimation
      of compartmental half-lives, resulting minimum bloodborne dose, and an
      approximation of the duration of elevated body burdens. We estimated the dermal
      exposure route to account for 80% of the blood chloroform concentration and the
      transdermal diffusion efficiency from the water to the blood to in excess of 2%.
      Bromodichloromethane elimination was fitted to a two compartment model which
      provided evidence of a small, but measurable, body burden of this THM resulting
      from vigorous swim training. These results suggest that trihalomethane exposures
      for competitive swimmers under prolonged, high-effort training are common and
      possibly higher than was previously thought and that the dermal exposure route is
      dominant. The exposures and potential risks associated with this common
      recreational activity should be more thoroughly investigated.

PMID- 9288499
TI  - Methylsulfonyl metabolites of PCBs and DDE in human tissues.
AB  - Methylsulfonyl metabolites of chlorinated biphenyls (MeSO2-CBs) and p,p'-DDE
      (MeSO2-DDEs) were determined in human adipose and liver tissues obtained at
      autopsy of seven Swedish individuals 47-80 years of age. Twenty MeSO2-CBs and two
      MeSO2-DDEs were found in the analyzed samples. In adipose tissue, most of the 4
      MeSO2-CBs were found at higher concentrations than the corresponding 3-MeSO2-CBs
      and, in all samples of adipose tissue, 4-MeSO2-2,2',3',4',5-pentaCB (4-87) and 4
      MeSO2-2,2',3,4',5',6-hexaCB (4-149) occurred at higher concentrations than other
      MeSO2-CBs. In the liver, 3-MeSO2-2,2',3',4',5,6-hexaCB (3-132) was by far the
      most abundant MeSO2-CB, contributing to 61-82% of the sum of MeSO2-CBs. In this
      tissue, most of the other 3-MeSO2-CBs were also found at higher concentrations
      than the corresponding 4-MeSO2-CBs. The ratios of the sum of MeSO2-CBs to the sum
      of determined chlorinated biphenyls (CBs) were 1/250 and 1/28 in adipose tissue
      and the liver, respectively, calculated from the median values. The concentration
      of 2-MeSO2-DDE was lower than that of 3-MeSO2-DDE in both adipose tissue and
      liver, except in the liver from one of the individuals. The concentration ratios
      of 2-MeSO2-DDE to 3-MeSO2-DDE were about 10 times higher in liver than in adipose
      tissue. The ratios of the sum of MeSO2-DDEs to p,p'-DDE were 1/455 and 1/61 in
      adipose tissue and liver, respectively, calculated from the median values. MeSO2
      CBs and MeSO2-DDEs were also determined in lung tissue from one of the
      individuals. In this sample, the profiles of MeSO2-CBs and MeSO2-DDEs were
      similar to the profiles of these compounds in adipose tissue.

PMID- 9288497
TI  - The effect of outdoor fungal spore concentrations on daily asthma severity.
AB  - The relationship between day-to-day changes in asthma severity and combined
      exposures to community air pollutants and aeroallergens remains to be clearly
      defined. We examined the effects of outdoor air pollutants, fungi, and pollen on
      asthma. Twenty-two asthmatics ages 9-46 years were followed for 8 weeks (9 May-3
      July 1994) in a semirural Southern California community around the air inversion
      base elevation (1,200 ft). Daily diary responses included asthma symptom severity
      (6 levels), morning and evening peak expiratory flow rates (PEFR), and as-needed
      beta-agonist inhaler use. Exposures included 24-hr outdoor concentrations of
      fungi, pollen, and particulate matter with a diameter < 10 microns (PM10; maximum
      = 51 micrograms/m3) and 12-hour day-time personal ozone (O3) measurements (90th
      percentile = 38 ppb). Random effects longitudinal regression models controlled
      for autocorrelation and weather. Higher temperatures were strongly protective,
      probably due to air conditioning use and diminished indoor allergens during hot,
      dry periods. Controlling for weather, total fungal spore concentrations were
      associated with all outcomes: per minimum to 90th percentile increase of nearly
      4,000 spores/m3, asthma symptom scores increased 0.36 (95% CI, 0.16-0.56),
      inhaler use increased 0.33 puffs (95% CI, -0.02-0.69), and evening PEFR decreased
      12.1 l/min (95% CI, -1.8-22.3). These associations were greatly enhanced by
      examining certain fungal types (e.g., Alternaria, basidiospores, and hyphal
      fragments) and stratifying on 16 asthmatics allergic to tested deuteromycete
      fungi. There were no significant associations to low levels of pollen or O3, but
      inhaler use was associated with PM10 (0.15 inhaler puffs/10 micrograms/m3; p <
      0.02). These findings suggest that exposure to fungal spores can adversely effect
      the daily respiratory status of some asthmatics.

PMID- 9288500
TI  - Intercomparison of analytical methods for arsenic speciation in human urine.
AB  - An intercomparison exercise was conducted for the quantification of arsenic
      species in spiked human urine. The primary objective of the exercise was to
      determine the variance among laboratories in the analysis of arsenic species such
      as inorganic As (As+3 and As+5), monomethylarsonic acid (MMA), and
      dimethylarsinic acid (DMA). Laboratories that participated had previous
      experience with arsenic speciation analysis. The results of this interlaboratory
      comparison are encouraging. There is relatively good agreement on the
      concentrations of these arsenic species in urine at concentrations that are
      relevant to research on the metabolism of arsenic in humans and other mammals.
      Both the accuracy and precision are relatively poor for arsenic concentrations of
      less than about 5 micrograms/l.

PMID- 9288501
TI  - Springtime peaks of trace metals in Antarctic snow.
AB  - Drifting snow samples were collected at Asuka Station (71 degrees 32'S, 24
      degrees 08'E, 930 m above sea level) over a period from July to December 1991; 36
      elements (including Na, Mg, K, Ca, Fe, Al, Li, V, Cr, Mn, Co, Ni, Cu, Zn, Ga, Se,
      Rb, Sr, Cd, Pb, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, and
      Th) in snow were analyzed by inductively coupled plasma-mass spectrometry (ICP
      MS) by direct sample introduction. Concentrations of Cl-, NO3-, and SO(4)2- in
      the snow were also determined by ion chromatography. In late September to early
      October, there was a pronounced peak concentration of most of the elements
      together with non-sea salt sulfate. Enrichment factor analyses suggest that Na,
      Mg, Ca, K, and Sr are of marine origin and Al, Fe, Mn, Rb, Cr, Ni, Ga, V, and all
      the rare earth elements are of crustal origins. Volcanic eruption of Mt. Pinatubo
      (June 1991) and Mt. Hudson (August 1991) could be the reason for the
      precipitation of Pb, Cd, Cu, Zn, and Se together with non-sea salt sulfates in
      the austral spring at Asuka Station.

PMID- 9288502
TI  - Atrioventricular septal defect and tetralogy of Fallot: a 15-year experience.
AB  - AIM: Atrioventricular septal defect and tetralogy of Fallot is a relatively
      uncommon lesion in which there is a risk of right ventricular dysfunction related
      to inlet and outlet valve problems. For this reason, conservative management
      involving an initial palliative procedure is often chosen. The aim of this report
      is to retrospectively review our experience with this lesion. PATIENT POPULATION:
      35 patients with atrioventricular septal defect and tetralogy of Fallot have been
      surgically managed at this institution between January 1980 and June 1995. Twenty
      one (60%) of these patients underwent 28 initial palliative shunt procedures.
      Fourteen (40%) patients underwent primary definitive repair. The criteria for
      choosing one management strategy over another was based on a number of factors,
      including age at presentation, anatomy of the lesion, and severity of symptoms.
      Of the 21 patients who underwent an initial shunt procedure, 15 have undergone
      definitive operation. Of the 6 patients who did not undergo definitive operation,
      three died (two directly related to complications of the shunt procedure), two
      are awaiting operation, and one was lost to follow-up. RESULTS: The primary
      indication for operation in all patients was cyanosis. Freedom from reoperation
      at 5 years after definitive operation was 65.1% for all patients; most
      reoperations were related to left atrioventricular valve regurgitation or
      residual leaks across the ventricular septal defect patch. The operative
      mortality at definitive operation was 10.3% (70% CL 4.5-20%) for all patients.
      The actuarial estimate of survival 7 years following definitive repair was 77.3%
      (70% CL 68.7-85.9%) for all patients. The actuarial estimate of survival at 7
      years was 84.4% (70% CL 73.8-95%) in the patients undergoing primary repair and
      65% (70% CL 52.4-77.6%) in patients initially palliated if the mortality of the
      palliative shunt procedure is included (P = 0.35). CONCLUSION: Patients with
      atrioventricular septal defect and tetralogy of Fallot can be successfully
      managed with a variety of surgical strategies. Primary repair may be a reasonable
      option in carefully selected patients, as this eliminates the morbidity and
      mortality of an initial shunt procedure and the subsequent interval between
      initial palliation and definitive repair.

PMID- 9288503
TI  - Bidirectional Glenn followed by total cavopulmonary connection or primary total
      cavopulmonary connection?
AB  - OBJECTIVE: Analysis of mortality and morbidity of patients treated by primary
      total cavopulmonary connection (TCPC)-Primary correction group, and comparison to
      patients treated by bidirectional Glenn (BDG) followed by total cavopulmonary
      connection-two stage TCPC group. METHODS: Retrospective study of 123 consecutive
      patients who underwent 144 different types of cavopulmonary connections between
      1987-1995: bidirectional Glenn 59, HemiFontan operation 10, primary total
      cavopulmonary connection 54, and total cavopulmonary connection completion after
      previous bidirectional Glenn 21. Important preoperative risk factors: age,
      systemic outflow obstruction, pulmonary venous obstruction, pulmonary artery (PA)
      hypoplasia (McGoon ratio), PA stenosis/distortion, PA mean pressure, PA vascular
      resistance, atrioventricular valve regurgitation, systolic and diastolic
      ventricular function and ventricular hypertrophy were re-evaluated according to
      Texas Heart Institution Scoring System in both groups. Three different
      preoperative risk groups were established: low risk, score (0-3) moderate risk
      (4,5) and high risk score (> or = 6). RESULTS: Mean age was 85.2 month (range
      16.1-229.5 months) and 106.6 months (range 42.6-178.9 months) in primary
      correction group and two stage TCPC group, respectively. Diagnosis was similar in
      both groups, majority having univentricular heart or hypoplastic one ventricle.
      Initial palliation (pulmonary artery banding, modified aortopulmonary shunt,
      coarctation repair etc.) was performed in 38 (70.3%) patients of primary
      correction group and in 12 (57.1%) two stage TCPC group. The mortality was 7.4%
      (4 out of 54) and 14.2% (3 out of 21) for primary correction and two stage TCPC
      group, respectively. There were two take down in the primary correction group.
      There was no late death in either group. Operative data and postoperative
      morbidity did not statistically differ in both groups. CONCLUSION: Until 1993
      bidirectional Glenn was preferred to primary total cavopulmonary connection for
      high risk patients. High mortality 14.2% patients of two stage TCPC group vs.
      7.4% of primary correction group in patients with the same preoperative hazard
      led us to change our policy. We now prefer primary TCPC for all patients with
      functional single ventricle and surgically correctable major associated defects.
      High risk patients undergo TCPC with fenestration. Patients not suitable for TCPC
      undergo either HemiFontan operation or some type of initial palliative procedure.

PMID- 9288504
TI  - Good exercise tolerance and impaired lung function after atrial repair of
      transposition.
AB  - OBJECTIVE: Evaluation of long-term results of atrial correction of transposition
      of the great arteries (TGA), focusing on the relationship between pulmonary
      function and exercise tolerance. METHODS: A prospective population-based study-56
      out of 60 survivors of Mustard/Senning repair, born in Bohemia in 1980-1984
      (median age at surgery 0.85 years) were followed up over 13.4 +/- 1.2 years and
      studied by complete lung function and bicycle exercise testing. RESULTS: Maximum
      heart rate on exercise reached 181 +/- 14 bpm (Z-score: -1.06 +/- 1.66, range 
      6.7 to +1.6); VO2max: 40.6 +/- 6.7 ml/kg per min (Z-score: -0.97 +/- 1.4, range 
      5 to +1.8). A total of 73.6% had abnormal lung function, most frequently features
      of stiff lung (39.6%) and lung restriction (32.1%). Static recoil pressure of the
      lungs measured at 100, 90 and 60% of total lung capacity reached 137, 126 and
      130%, respectively (Z-score: 1.93 +/- 2.33, 1.64 +/- 1.96, and 1.14 +/- 1.95,
      respectively). There was an inverse relationship between static recoil pressure
      of the lungs and VO2max (r = -0.306, P = 0.043), indicating the impact of lung
      function abnormalities on exercise tolerance. Comparison with lung function study
      of the group of 'pioneer' Mustard patients operated at the mean age of 4.4 years
      revealed a similar pattern and frequency (73.6% in current series vs. 88%, NS).
      CONCLUSIONS: Long-term follow-up has shown good exercise tolerance in the
      majority of patients after atrial correction of TGA performed in infancy. Many of
      them, however, have impaired lung function, especially stiff lung, although less
      frequently than original patients operated at a later age. The stiff lung can
      impair the exercise tolerance.

PMID- 9288505
TI  - Evaluation of gastric intramucosal pH during and after pediatric cardiac surgery.
AB  - OBJECTIVES: In adult patients, intramucosal pH (pHi) has been advocated to detect
      postoperative complications. The purpose of our study was to evaluate this
      technique in pediatric patients during and after cardiac surgery. METHODS: Thirty
      five infants (age: 5 days to 15 years, median 1.8 years; and weight: 3.2-32 kg,
      median 9.8 kg) were studied. pHi was measured before cardiopulmonary bypass
      (CPB), after 30 min of CPB, prior to weaning off CPB, at intensive care unit
      arrival, and 6, 12, 24, 48 and 72 h after surgery. RESULTS: There were no
      complications related to the tonometer. A pathologically low pHi < 7.32 was found
      during surgery in less than 17%, at intensive care unit arrival in 83% and after
      48 h in 18%. pHi values were lower (P < 0.05) at intensive care unit arrival
      (7.25 +/- 0.08) and after 6 h (7.28 +/- 0.09) than afterwards. pHi correlated
      with arterial pH (r = 0.66), central-peripheral temperature difference (r = 
      0.36), lactate (r = -0.32) and central venous pressure (r = -0.21). Patients
      after a Fontan procedure had postoperatively a lower pHi than after other
      operations (P < 0.05). None of the patients died or developed organ failure. Six
      patients had signs of organ dysfunction. Their pHi (median 7.23, range 7.14-7.28)
      could not differentiate them from the other patients. CONCLUSIONS: With current
      equipment, tonometry cannot be recommended for the management of pediatric
      patients after cardiac surgery. However, as a semi-invasive method tonometry
      deserves further evaluation.

PMID- 9288507
TI  - Aortic dissection type A versus type B: a different post-surgical death hazard?
AB  - OBJECTIVE: Patients with type B aortic dissection differ from patients with type
      A dissection in age, hypertension prevalence, indications and timing of surgical
      treatment, yet reported long-term results have been rather similar (see Doroghazi
      et al. J Am Coll Cardiol 1984;3:1026-1034). METHODS: With the aim of comparing
      the post-surgical history, we have reviewed our results in 288 dissections, 213
      type A and 75 type B, operated consecutively between 1 January 1970 and 31
      November 1994. Follow-up was 100% complete. Empirical survival of both groups was
      interpolated with a fully parametric method and the shape and scale of the hazard
      function was investigated. RESULTS: Survival was not significantly different
      between type A and type B. Parametric survival was, respectively, 0.52% (70%
      C.L.: 0.48-0.55) vs. 0.56% (0.51-0.62) at 5 years, 0.44% (0.40-0.47) vs. 0.28%
      (0.23-0.25) at 10 years, 0.37% (0.33-0.41) vs. 0.25% (0.19-0.32) at 15 years, and
      0.31% (0.26-0.35) vs. 0.24% (0.18-0.31) at 20 years. Following the high
      perioperative risk phase in type A dissection, the intermediate and late risk
      remains constant at a rate of 0.0033 events/month (3.9% patient-years (pt.
      years)). By contrast, the postoperative course of type B dissection shows an
      intermediate risk phase between 4 and 10 years with an average linearized risk of
      9.3% pt.-years and a peak of 20%. This determined lower survival rates (24 vs.
      31% at 20 years, P = NS). CONCLUSIONS: We conclude that patients with type B
      dissection have a steeper postoperative death hazard as compared to type A
      dissection patients. Age confounding or late entry do not explain the difference.
      This could be possibly related to a greater propensity for expansion, higher risk
      of malperfusion complications or to limitations of our current surgical
      treatment.

PMID- 9288506
TI  - Aortobronchial and aortoesophageal fistulae as risk factors in surgery of
      descending thoracic aortic aneurysms.
AB  - OBJECTIVE: Assess outcome of patients with descending thoracic aortic aneurysms
      complicated by aortobronchial and aortoesophageal fistulae in comparison to
      patients undergoing repair of aortic aneurysms without fistulae. METHODS: In a
      consecutive series of 145 patients (age 60 +/- 12 years) with repair of
      descending thoracic and thoracoabdominal aortic aneurysms, 11 patients (8%; age
      63 +/- 9; NS) primarily presented for hematemesis and/or hemoptysis. In 8/11
      patients (73%) an aortobronchial fistula was identified, and 3/11 patients (27%)
      suffered from an aortoesophageal fistula. Five of 11 patients (45%) had undergone
      previous aortic surgery in the same region. RESULTS: Extent of aortic segments
      (range 1-8) replaced was 3.1 +/- 1.4 for all versus 2.6 +/- 0.9 for fistulae
      (NS). Aortic cross clamp time was 38 +/- 22 min for all versus 45 +/- 15 min for
      fistulae (NS). Mortality at 30 days was 18/145 (12%) for all versus 16/134 (12%)
      without fistulae versus 2/11 (18%) with fistulae (NS). Paraparesis and or
      paraplegia was observed in 11/145 (8%) for all versus 10/134 (7%) without
      fistulae versus 1/11 (9%) for cases with fistulae (NS). Nine additional patients
      died after hospital discharge, seven without fistulae and two with fistulae (days
      80, and 120) bringing the 1-year mortality up to 23/134 (17%) without fistulae
      versus 4/11 (36%) with fistulae (NS). Further analysis shows that the 1-year
      mortality accounts for 1/8 patients (13%) with aorto-bronchial fistulae versus to
      3/3 patients (100%) with aorto-esophageal fistulae (esophageal versus bronchial
      fistula: P = 0.018; esophageal versus no fistula: P = 0.006). CONCLUSIONS:
      Outcome of patients suffering from descending thoracic aortic aneurysms
      complicated by aorto-bronchial fistulae can be similar to that without fistulae,
      whereas for cases complicated by aorto-esophageal fistulae the prognosis seems to
      remain poor even after successful hospital discharge.

PMID- 9288508
TI  - Pneumonectomy for tuberculosis.
AB  - OBJECTIVE: Surgery for tuberculosis has been of major concern because of its
      associated morbidity and mortality, particularly with respect to pneumonectomy.
      METHODS: Over a period of 11 years, between January 1985 and December 1995,
      pneumonectomy was performed for 20 patients with documented history of
      mycobacterium tuberculosis (TB). There were 12 male and eight female patients
      with an average age of 28.7 years. All patients had productive cough for an
      average duration of 12.8 years, while ten (50%) had an additional hemoptysis for
      an average duration of 3.9 years. Four patients (20%) were still with positive
      acid-fast bacilli due to drug resistance and four (20%) had aspergilloma complex.
      Preoperatively, all patients showed radiological evidence of unilateral destroyed
      lung with no perfusion. RESULTS: Among the 20 patients with post-tuberculosis
      lung destruction, 16 had left lung destruction and four had the right lung
      destroyed. In this series, there was no mortality and morbidity accounted for 15%
      (n = 3). Two patients required re-exploration for bleeding, while one patient
      developed post-pneumonectomy empyema without bronchopleural fistula, for which
      drainage with rib resection was performed. All patients were found to be symptom
      free during the follow up period which averaged 93.7 +/- 23.9 months (range
      between 12 and 124 months). CONCLUSIONS: In this series of 20 patients,
      pneumonectomy for TB and post-tuberculosis lung destruction was performed with no
      mortality and acceptable morbidity. Meticulous surgical technique is mandatory to
      avoid operative complications. Persistent positive sputum for acid-fast bacilli
      should not be considered as contraindication in symptomatic patients.

PMID- 9288509
TI  - Is there a role for video-assisted thoracoscopy in the staging of non-small cell
      lung cancer?
AB  - OBJECTIVE: To evaluate the role of video-assisted thoracoscopy (VAT) in the
      staging of non-small cell lung cancer (NSCLC). METHODS: In 30 patients (18 male,
      12 female, median age 62 (50-78) years) VAT was used to assess the operability of
      NSCLC in cases where doubt existed after conventional staging investigations had
      been performed. RESULTS: VAT was used to assess direct tumour invasion of
      adjacent organs in 17 patients (mediastinal invasion in 14 and chest wall
      invasion in 3 patients). In 4 patients with limited respiratory reserve, VAT
      confirmed the need only for lobectomy prior to thoracotomy. Mediastinal lymph
      node biopsy was performed in 5 patients with significant (> 1.5 cm)
      lymphadenopathy on CT scan. VAT was also used to assess bilateral lesions in 4
      patients with suspected synchronous tumours. Conversion to thoracotomy was
      necessary in 4 patients for technical reasons. Successful resection was possible
      in 17 of the remaining 26 cases, while unnecessary thoracotomy was avoided in 9
      patients (30%) with unresectable or benign disease. In 4 patients deemed
      inoperable on CT scan, VAT staging enabled subsequent resection. CONCLUSIONS:
      Video-assisted thoracoscopy appears to have a complementary role in staging NSCLC
      when other methods are equivocal. It has the potential for increased sensitivity
      over conventional staging methods.

PMID- 9288510
TI  - Prognosis of ipsilateral intrapulmonary metastases in resected nonsmall cell lung
      cancer.
AB  - OBJECTIVE: According to the new classification of intrapulmonary metastasis (pm)
      of lung cancer by the American Joint Committee on Cancer (AJCC), ipsilateral pm
      is classified as a T factor. We evaluated the prognostic factors of ipsilateral
      pm after surgical treatment, and validity of the new classification. METHODS:
      From January 1977 to December 1994, 41 patients (24 males and 17 females) with
      lung cancer had a postoperative diagnosis of intrapulmonary pm. The histologic
      type consisted of 27 adenocarcinoma. 12 squamous cell carcinoma, and 1 large cell
      carcinoma. Twenty patients had pm in the same lobe in which the primary lesion
      was located, and 21 patients had pm in ipsilateral different lobe(s). Thirty
      patients underwent lobectomy, 5 bilobectomy and 6 pneumonectomy. Survival was
      calculated by the Kaplan Meier method, and Cox proportional hazards model was
      used for multivariate analysis. RESULTS: The overall survival was 25.8% at 5
      years (median survival time (MST), 26 months). The 3-year survival of patients
      with pm in the same lobe was 49% (MST, 33 months), and that of patients with
      different lobe was 21% (MST, 16 months) (P = 0.237). There were no significant
      differences in survival in relation to age, sex, histology, pathological N
      factor, or number of pm. Multivariate analysis identified a significant
      correlation between survival and T factor proposed by AJCC (P = 0.022).
      CONCLUSIONS: The new classification seems useful for estimating postoperative
      prognosis of the resected patients with lung cancer accompanied by ipsilateral
      pm.

PMID- 9288512
TI  - Thromboxane A2-receptor blockade improves cerebral protection for deep
      hypothermic circulatory arrest.
AB  - OBJECTIVE: Following the use of deep hypothermic circulatory arrest in cardiac
      surgery, cerebral blood flow and cerebral oxygen metabolism are impaired. These
      may result from abnormal cerebral vasospasm. Powerful vasoconstrictors including
      endothelins and thromboxane A2 could mediate these processes. We investigated
      possible involvement of these two factors by assessing the effects of (a)
      phosphoramidon-an inhibitor of endothelin converting enzyme, and (b) vapiprost
      (GR32191B)-a specific thromboxane A2-receptor antagonist, on the recovery of
      cerebral blood flow and cerebral oxygen metabolism following deep hypothermic
      circulatory arrest. METHODS: A total of 18 1-week-old piglets were randomised
      into three groups (n = 6 per group). At induction, the control group received
      saline; group PHOS received phosphoramidon 30 mg kg-1 intravenously. Group VAP
      received vapiprost 2 mg kg-1 at induction and at 30 min intervals thereafter. All
      groups underwent cardiopulmonary bypass cooling to 18 degrees C, exposed to 60
      min of deep hypothermic circulatory arrest, rewarmed and reperfused for 1 h.
      Cerebral blood flow was measured with radio-labeled microspheres: cerebral oxygen
      metabolism was calculated at baseline before deep hypothermic circulatory arrest
      and at 1 h of reperfusion and rewarming. RESULTS: In the control group, cerebral
      blood flow decreased to 40.2 +/- 2.0% of baseline after deep hypothermic
      circulatory arrest and cerebral oxygen metabolism decreased to 50.0 +/- 5.5% (P <
      0.0005). The responses in group PHOS were similar. In group VAP, cerebral blood
      flow and cerebral oxygen metabolism were 64.3 +/- 10.6 and 80.1 +/- 9.8% of
      baseline, respectively, after deep hypothermic circulatory arrest. Thus,
      treatment with vapiprost significantly improved recovery of cerebral blood flow
      (P = 0.046) and cerebral oxygen metabolism (P = 0.020) following deep hypothermic
      circulatory arrest. No such improvement was seen after treatment with
      phosphoramidon. CONCLUSIONS: Thromboxane A2 mediates impairments in cerebral
      perfusion and metabolism following deep hypothermic circulatory arrest. These
      changes were attenuated by blockade of thromboxane A2-receptors using vapiprost.
      Endothelins are not shown to be involved. Better knowledge of injury mechanisms
      will enable development of more effective cerebral protection strategies and
      allow safer application of deep hypothermic circulatory arrest.

PMID- 9288513
TI  - Near-infrared monitoring of myocardial oxygenation during intermittent warm blood
      cardioplegia.
AB  - OBJECTIVE: This study was performed to examine the ability of near-infrared
      spectroscopy to monitor tissue oxygenation in the cardioplegically arrested heart
      and to assess myocardial oxygen metabolism during intermittent warm blood
      cardioplegia. METHODS: Using a three-wavelength near-infrared spectroscopy, we
      continuously measured myocardial tissue oxygen saturation and the tissue
      hemoglobin concentration during intermittent warm blood cardioplegia. Under
      normothermic cardiopulmonary bypass, 20 dogs received three 5-min periods of
      antegrade warm blood cardioplegia, interrupted by three 10-min episodes of
      ischemia in group 1 (n = 7), three 15-min episodes of ischemia in group 2 (n =
      6), or three 20-min episodes of ischemia in group 3 (n = 7). RESULTS: Myocardial
      oxygen saturation during beating and ventricular fibrillation was 80 +/- 1 and 59
      +/- 1%, respectively. Myocardial oxygen saturation rapidly increased to 82 +/- 1%
      at blood cardioplegic infusion and decreased to 58 +/- 1% 3 min after
      cardioplegic interruption. The time required to reach the peak oxygen saturation
      level decreased significantly at the second and third infusions compared to the
      first infusion in group 1, whereas the time increased significantly at the third
      infusion in groups 2 and 3. The slower rate of increase in oxygen saturation
      suggested reduced coronary vasodilator reserve due to microvascular
      abnormalities. Reperfusion ventricular fibrillation occurred in none of group 1,
      one of group 2 and three of group 3. CONCLUSIONS: Near-infrared spectroscopy is a
      useful method of continuously monitoring myocardial oxygenation and ischemia
      during warm heart surgery. Episodes of ischemia longer than 10 min during warm
      blood cardioplegia resulted in less-than-optimal myocardial preservation and
      should be avoided.

PMID- 9288511
TI  - Comparison of imaging TNM [(i)TNM] and pathological TNM [pTNM] in staging of
      bronchogenic carcinoma.
AB  - OBJECTIVE: Precise tumor (T) and nodal (N) staging is imperative in non-small
      cell lung cancer (NSCLC) as it determines subsequent treatment, certainly when
      considering neoadjuvant treatment for stage IIIA or IIIB disease. To determine
      the accuracy of present-day computed tomographic (CT) scanning a prospective
      study was performed comparing imaging TNM [(i)TNM] and pathological TNM [pTNM].
      METHODS: In 74 patients with NSCLC without distant metastases (i)TNM was
      determined on CT findings. The TNM system advocated by the American Joint
      Committee on Cancer was used. All patients underwent cervical mediastinoscopy.
      When superior mediastinal nodes were negative this was followed by thoracotomy
      and pathological examination of the resected specimen and lymph nodes to
      determine pTNM. RESULTS: The agreement between (i)TNM and pTNM was only 35.1%.
      The primary tumor (T) was correctly staged in 54.1%, overstaged in 27.0% and
      understaged in 18.9% of the patients. Invasion of chest wall, pericardium and of
      major mediastinal structures (T3, T4) was not reliably detected by CT scan.
      Sensitivity and specificity of CT regarding hilar and mediastinal lymph node
      staging were 48.3 and 53.3%, positive and negative predictive value 40 and 61.1%
      and its overall accuracy 51.4%. The nodal (N) factor was correctly determined by
      CT scan in 35.1%, overstaged in 44.6%, and understaged in 20.3% of the patients.
      CONCLUSIONS: Even with present-day CT scanners (i)TNM provides no accurate
      staging and routine mediastinoscopy is necessary for precise mediastinal lymph
      node staging. Likewise, (i)T3 and (i)T4 determinations are unreliable and should
      not contraindicate thoracotomy.

PMID- 9288514
TI  - Assessment of myocardial distribution of retrograde and antegrade cardioplegic
      solution in the same patients.
AB  - OBJECTIVE: In order to clarify intramyocardial delivery and distribution of
      retrograde cardioplegic solution in humans, we induced both ante- and retrograde
      methods in the same patients to compare their respective delivery and
      distribution using myocardial contrast echocardiography during surgery. METHODS:
      15 patients consisting of nine patients with valvular heart diseases and six
      patients with coronary artery diseases (including two patients with myocardial
      infarcted areas and two patients with areas supplied by coronary collateral
      situation associated with totally occluded coronary arteries without myocardial
      infarction). Induction of cardioplegia was initially accomplished antegradely and
      thereafter retrogradely. RESULTS: In valvular heart disease, retrograde
      cardioplegic solution was distributed less homogeneously, and was not delivered
      to the midportion of the interventricular septum in two-thirds of the patients
      (6/9). The transmural myocardial distribution in the anterior, lateral, and
      posterior walls in the left ventricle were similar for both ante- and retrograde
      cardioplegic solution, while delivery to the endocardial halves was better than
      to the epicardial halves (endo-/epicardial intensity ration in antegrade versus
      retrograde: 1.31 +/- 0.24 versus 1.29 +/- 0.26; 1.19 +/- 0.05 versus 1.36 +/-
      0.23; 1.33 +/- 0.28 versus 1.44 +/- 0.35, respectively (all NS)). For delivery to
      the right ventricle, the existence of small cardiac vein was important. In
      patients with small cardiac vein (34% in our study), the delivery to the right
      ventricular dorsal walls was shown. In coronary heart disease, retrograde
      cardioplegic solution was well delivered to the areas by coronary collateral
      situation associated with totally occluded coronary arteries, but antegrade
      solution was not. Neither ante- nor retro grade solution was delivered to
      myocardial infarcted areas. CONCLUSIONS: These results have important
      implications for planning strategies for myocardial protection. We think that it
      is necessary to fully grasp the coronary arterial and venous anatomy of
      individual patients and to know how to use either ante- or retrograde
      cardioplegia properly.

PMID- 9288516
TI  - Cardiac troponin T and troponin I release during coronary artery surgery using
      cold crystalloid and cold blood cardioplegia.
AB  - OBJECTIVE: To evaluate and compare myocardial protection using cold crystalloid
      and blood cardioplegia by measuring release of cardiac Troponin T and Troponin I
      during coronary artery surgery. METHODS: Forty two patients undergoing myocardial
      revascularization were prospectively randomised into two groups in whom
      myocardial protection was achieved with either antegrade cold (4 degrees C)
      crystalloid (CCP) (n = 21) St. Thomas' I cardioplegic solution. Serial venous
      blood samples were collected for measurement of cardiac Troponin T and Troponin
      I, prior to induction of anesthesia and at 4, 12, 24 and 48 h after removal of
      the aortic cross clamp. RESULTS: There were no hospital deaths in the two groups
      and one patient in each group suffered a perioperative myocardial infarction.
      Rising levels of Troponin T and Troponin I were found in all patients. Serum
      concentrations increased as early as 4 h after removal of the aortic cross clamp,
      and reached a peak at 12 h postoperatively in both groups. These levels
      subsequently declined, but remained higher than preoperative values at 48 h.
      There were no differences between the two groups with respect to serum Troponin T
      and I release at 4, 12, 24 and 48 h, area under the respective curves, and peak
      Troponin T and I release. Serum Troponin levels were significantly higher in
      patients with unstable angina and in two patients who suffered a perioperative
      myocardial infarction. CONCLUSION: Serum release of cardiac Troponin T and
      Troponin I is significantly raised in low risk patients undergoing myocardial
      revascularization. This release is similar when either cold crystalloid or cold
      blood cardioplegia are used. This may imply that both methods offer identical
      protection to the myocardium in a low risk group of patients.

PMID- 9288515
TI  - Lipid peroxidation, antioxidant status and troponin-T following cardiopulmonary
      bypass. A comparison between intermittent crossclamp with fibrillation and
      crystalloid cardioplegia.
AB  - OBJECTIVE: Intermittent crossclamp with fibrillation affords equivalent
      myocardial protection to cold crystalloid cardioplegia in patients undergoing
      elective coronary artery surgery. This study is a direct comparison between the
      two techniques with regards to free radical activity. METHODS: The study design
      was part of a prospective randomised trial. We studied 24 consecutive patients
      with ejection fraction of 30% or greater undergoing elective coronary artery
      surgery. Patients were randomised into two groups. In group 1 (n = 13) the
      myocardium was protected by intermittent aortic cross clamping with fibrillation
      and group 2 (n = 11) by antegrade cold crystalloid cardioplegia. The determinants
      of free radical activity were serial peripheral venous samples for lipid
      peroxidation and plasma antioxidant status (before and at 1, 6, 24 and 72 h after
      the end of cardiopulmonary bypass). The determinant of the efficacy of myocardial
      protection was serial peripheral venous samples of cardiac troponin-T taken at
      the same time intervals. RESULTS: The groups were similar with respect to age,
      sex distribution, preoperative ventricular function, left main stem disease,
      number of grafts and bypass times. Lipid peroxidation measurements at the 1 h
      time point were higher than preoperative values (7.24 +/- 1.19 vs. 4.48 +/- 0.69
      and 9.36 +/- 1.46 vs. 4.98 +/- 1.02 (mean +/- S.E) in groups 1 and 2,
      respectively (units in mmol/l) thereafter values decreased to near preoperative
      values by 72 h. There was no significant difference between the groups (P =
      0.42). Total plasma antioxidant status values at the 1 h time point were lower
      than the preoperative values for all patients (1.33 +/- 0.07 vs. 1.63 +/- 0.06
      and 1.42 +/- 0.07 vs. 1.63 +/- 0.05 (mean +/- standard error) in groups 1 and 2,
      respectively, (units in mmol/l) and thereafter at the subsequent time points
      increased but never attained their preoperative value. There was no statistically
      significant difference between the two groups (P = 0.59). Troponin-T measurements
      showed no significant difference between the two groups at all time points (P =
      0.2217). CONCLUSIONS: This study shows that lipid peroxidation is initially
      elevated and the defence mechanisms against oxygen free radicals-antioxidant
      status'-are depressed following cardiopulmonary bypass. The degree of oxygen free
      radical activity produced during ischaemia and reperfusion was similar in both
      types of myocardial protection employed in this study.

PMID- 9288517
TI  - Induction of early immediate genes and programmed cell death following
      cardioplegic arrest in human hearts.
AB  - OBJECTIVE: Under experimental conditions cardiac stress may induce early
      immediate genes. Of these, heat shock proteins like hsp 70 have been linked to
      preconditioning and cellular salvage. Protooncogenes like c-fos and c-jun act as
      transcription factors for other genes and may be involved in the regulation of
      programmed cell death. METHODS: Patients, 30, undergoing elective coronary artery
      bypass grafting, received either cold antegrade St. Thomas II or Bretschneider or
      Hamburg cardioplegic solutions with ten patients in each group. Tissue from right
      atria was removed before cardiopulmonary bypass and following cardioplegic arrest
      and reperfusion. Tissues were examined by Northern blots, immunohistochemistry,
      and in situ nick-end labeling of fragmented DNA as evidence for programmed cell
      death. RESULTS: There were no significant preoperative or operative differences
      between groups. Following cardioplegia and reperfusion, a significant induction
      of both protooncogene and heat shock protein 70 mRNA was observed. Whereas levels
      of hsp 70 were increased about two-fold in all groups (P < 0.05), induction of c
      fos and c-jun was most pronounced following the Hamburg cardioplegic solution (P
      < 0.05 versus baseline and for differences to other groups). Induction on the
      protein level was confirmed using immunohistochemistry that furthermore,
      identified cardiac myocytes and endothelial cells being the cell types that
      expressed these genes. In contrast to prebypass samples, in situ nick-end
      labeling of fragmented DNA following cardioplegic arrest and reperfusion was
      positive, preponderately in subendocardial myocytes and endothelial cells.
      CONCLUSIONS: Cold cardioplegia is a potent stimulus for induction of the early
      immediate genes examined in human hearts. Increased expression of protooncogenes
      may be deleterious to cardiac myocytes as indicated by in situ nick-end labeling
      of DNA fragments. Differences in gene induction may add additional information
      for the evaluation of different cardioplegic strategies.

PMID- 9288518
TI  - Cell activation and thrombin generation in heparin bonded cardiopulmonary bypass
      circuits using a novel in vitro model.
AB  - OBJECTIVE: It is generally agreed that when the blood contact surfaces of a
      cardiopulmonary bypass circuit are treated with a layer of heparin molecules the
      activation of the humoral pathways is attenuated. However, there is still debate
      as to whether heparin-bonded circuits reduce thrombin generation. This study aims
      to examine the effects of immobilized heparin on cell activation and thrombin
      generation in a novel, well controlled model of cardiopulmonary bypass. METHODS:
      The model used consisted of a heparin-bonded and a non-bonded cardiopulmonary
      bypass circuit perfused in tandem with the same unit of fresh heparinized (3.3
      U/ml) human blood for a period of 6 h. Samples were taken for analysis from the
      bag just prior to perfusion and at 30, 60, 120 and 360 min of perfusion. Whole
      blood was used to analyse platelet and white blood cell count, haematocrit and
      activated coagulation time. Plasma samples were prepared for batch analysis of
      the cell activation markers p-selectin, elastase and interleukin-8, and the
      thrombin generation markers thrombin-antithrombin and prothrombin fragment F1 +
      2. A sample of tubing was taken from each circuit at the end of the perfusion and
      prepared for visualization by scanning electron microscopy. RESULTS: Platelet
      counts were significantly reduced in the non-bonded circuits compared with the
      heparin-bonded circuits at 30 (22 versus 200 x 10(9)/L P < 0.01), 60 (26 versus
      193 x 10(9)/L P < 0.01) and 120 min (28 versus 193 x 10(9)/L P < 0.01) as were
      white blood cell counts at 30(1.5 versus 2.7 x 10(9)/L P < 0.01), 60 (0.9 versus
      2.4 x 10(9)/L P < 0.01), 120 (0.9 versus 1.8 x 10(9)/L P < 0.01) and 360 min (0.4
      versus 0.9 x 10(9)/L P < 0.05). The concentration of p-selectin was found to be
      significantly higher in the non-bonded circuits than in the heparin-bonded
      circuits at 30 (37 versus 29 ng/ml P < 0.01), 60 (37 versus 28 ng/ml P < 0.01).
      120 (42 versus 27 ng/ml P < 0.01) and at 360 min (72 versus 46 ng/ml P < 0.01).
      Elastase was elevated in the non-bonded circuits at 30 (570 versus 145
      micrograms/l P < 0.01), 60 (646 versus 278 micrograms/l P < 0.01) and 120 min
      (613 versus 403 micrograms/l P < 0.05) and interleukin-8 at 120 (705 versus 520
      pg/ml P < 0.05) and 360 min (11326 versus 9910 pg/ml P < 0.05). A similar picture
      was found for the thrombin generation markers. Thrombin-antithrombin complexes
      were raised in the non-bonded circuits compared with heparin-bonded circuits at
      60 (24 versus 13 micrograms/l P < 0.05) and 120 min (46 versus 17 micrograms/l P
      < 0.05) as was prothrombin fragment F1 + 2 at 30 (1.1 versus 0.7 nmol/l P <
      0.01), 60 (1.3 versus 0.7 nmol/l P < 0.01), 120 (1.8 versus 0.9 nmol/l P < 0.01)
      and 360 min (15.0 versus 13.6 nmol/l P < 0.05). Scanning electron microscopy
      revealed a greater amount of adherent material on the non-bonded surface relative
      to the heparin-bonded surface. CONCLUSIONS: In a cardiopulmonary bypass circuit
      perfused with human blood the activation of platelets and white blood cells has
      been seen to be significantly reduced in the presence of a heparin-bonded
      surface. Thrombin generation due to contact activation of the intrinsic
      coagulation pathway is also reduced.

PMID- 9288519
TI  - Transmyocardial laser revascularisation combined with coronary artery bypass
      grafting without cardiopulmonary bypass.
AB  - OBJECTIVE: To achieve complete myocardial revascularisation in patients with
      diffuse coronary artery disease, patients with inordinately high risk of
      cardiopulmonary bypass (CPB) like severe systemic disease or diffuse
      atherosclerosis of the aorta. METHODS: We have adopted the technique of combining
      coronary artery bypass grafting (CABG) with transmyocardial laser
      revascularisation (TMLR) using 1000 W CO2 laser machine. TMLR is done to areas
      supplied by ungraftable arteries, while CABG without cardiopulmonary bypass is
      done to the left anterior descending artery (LAD) and/or right coronary artery
      (RCA). TMLR + CABG on beating heart without CPB has been performed on 56
      patients. Age ranged from 37 to 81 years with a mean of 56.17. Four patients were
      in renal failure, two were redo CABG. Preoperatively 39.28% patients had angina
      class III and 10.71% had angina class IV. Four patients were on preoperative IABP
      support. RESULTS: The mean number of grafts was 1.09. Internal thoracic artery
      (ITA) was used in 96.4% of the patients. Five patients showed elevation of CPK
      MB, while three patients had an increase in Troponin T. Mortality was 1.8% (one
      patient died of intractable ventricular arrhythmia). The mean follow-up is 9.2
      months. Myocardial perfusion scanning showed a stepwise improvement in reversible
      ischemia increasing from 52% at baseline to 91% at 12 months; 90.9% of the
      patients were angina free at 12 months. Metabolic stress test demonstrated an
      average increase in exercise tolerance from 5.2 min at baseline to 9.4 min at 12
      months. Metabolic equivalents (METs) increased from 4.5 at baseline to 9.4 at 12
      months. The average 44% Karnofsky score preoperative also increased to 86% at 12
      months. CONCLUSIONS: Our results indicate that the technique is surgically
      feasible and safe, with excellent short term results.

PMID- 9288520
TI  - Single-institution effectiveness assessment of open-heart surgery in
      octogenarians.
AB  - OBJECTIVE: To determine short- and long-term outcome of open-heart surgery in
      octogenarians. METHODS: We reviewed the medical charts of 130 consecutive
      octogenarians undergoing open-heart surgery. Patients with significant
      comorbidity were excluded from the study. The effect of cardiac and operative
      risk factors on mortality and morbidity was evaluated. General practitioners and
      cardiologists were contacted in order to obtain information on the patients'
      current medical and functional status. RESULTS: Operative mortality for valve
      replacement (VR) and coronary artery bypass grafting (CABG) was 11.5%. Four-year
      survival was 73.5% with 75.9% still living independently. The relative risk for
      operative mortality was 4.3 in case of extracorporeal bypass time exceeding 95
      min and 3.6 in case of significant left main stem disease. The risk of late death
      increased 2.5 times at a left ventricular ejection fraction lower than 50%.
      CONCLUSIONS: Our data match the results of similar studies involving large
      numbers of patients. When a multicenter data bank is missing, the evaluation of a
      relatively small patient group can yield information that may be as useful to
      patient and physician as information obtained by large studies. Open-heart
      surgery in octogenarians carries an acceptable mortality risk and its
      effectiveness in terms of improved quality of life is good.

PMID- 9288521
TI  - Left ventricular aneurysmectomy; comparison between two techniques; early and
      late results.
AB  - OBJECTIVE: The aim of the present study was to evaluate early and late results of
      two different surgical techniques for left ventricular aneurysms repair. The
      conventional aneurysmectomy and direct closure of the ventricular wall and the
      endoventricular patch plasty. METHODS: We retrospectively reviewed 118 patients
      operated on for postinfarction left ventricular aneurysm from 1981 to 1994.
      Eighty-seven patients (Group A) were operated upon between 1981 and 1991 with the
      conventional technique and 31 patients (Group B) between 1992 and 1994 with the
      endoventricular patch plasty technique. Preoperative clinical, hemodynamic and
      echocardiographic evaluation with operative procedures and early postoperative
      results of all patients are reported. We also analyzed results of late clinical
      and echocardiographic controls of 34 patients of Group A and all patients of
      Group B after a mean follow-up of 42 and 28 months, respectively. RESULTS: Mean
      number of by-pass grafts was 1.9 in Group A and 2.6 in Group B (P = 0.01). The
      left anterior descending coronary artery was revascularized in 27 patients of
      Group A (34.6%) and 26 of Group B (89.7%) (P < 0.001); the left internal mammary
      artery was used in seven patients of Group A (8.9%) and 24 of Group B (82.8%) (P
      < 0.001). Hospital mortality in Group A was 10.3% (9/87), in Group B there was no
      hospital mortality (P > 0.05). Thirty-two patients of Group A (36.8%) and 3 of
      Group B (9.7%) suffered of low cardiac output syndrome (P = 0.01). At late
      control, improvements observed in NYHA and CCS classes, left ventricular ejection
      fraction (all P < 0.001 in both groups versus preoperative values) and left
      ventricular end-diastolic diameter (P > 0.05 in Group A and P < 0.001 in Group B)
      proved to be statistically higher in patients of Group B. CONCLUSIONS:
      Endoventricular patch plasty associated with a complete myocardial
      revascularization, in particular of the anterior descending coronary, and a
      larger use of the internal mammary artery, permits, by means of reconstruction of
      the left ventricular geometry, a better outcome for patients undergoing left
      ventricular aneurysmectomy.

PMID- 9288522
TI  - Surgical treatment of acquired ventricular septal defects in the elderly.
AB  - OBJECTIVE: As the population continues to age, older patients are being referred
      for repair of acquired ventricular septal defect (VSD) following myocardial
      infarction (MI). The purpose of this study was to assess the effect of age (> or
      = 70 years) on operative risk and long term survival following repair of an
      acquired VSD. METHODS: Between January 1972 and December 1995, 179 patients have
      undergone repair of acquired VSDs following MI in our unit. There were 118 males
      and 61 females (age range 43-80 years) of whom 60 were aged 70 years or above.
      RESULTS: The overall early mortality was 27%. On univariate analysis risk factors
      for early death included shorter time from both MI and detection of murmur to
      operation (P < 0.01, P = 0.04), site of MI (P < 0.01), higher NYHA class (P <
      0.01), lower preoperative blood pressure (P < 0.01) and longer cardiopulmonary
      bypass and cross clamp times (P < 0.01, P = 0.03). Non significant variables
      included age, sex, concomitant CABG and preoperative renal function. Early
      mortality was 28.6% (34/119) in patients under 70 and 25.0% (15/60) in those over
      70. This difference was not significant. The only significant differences between
      the age groups were sex distribution (females > males, P < 0.01), in the older
      group, and shorter time from both MI and detection of murmur to operation (P =
      0.04, P = 0.02). Cardiopulmonary bypass was the only statistically significant
      variable on multivariate analysis (P = 0.01). CONCLUSIONS: There was no
      significant difference in early mortality between the two age groups. As shorter
      times from both MI and detection of murmur to operation adversely affect early
      mortality, age over 70 years should not be used to determine suitability for
      surgery.

PMID- 9288523
TI  - Predictors for recurrent chest pain and relationship to myocardial ischaemia
      during long-term follow-up after coronary artery bypass grafting.
AB  - OBJECTIVE: To describe the impact of coronary artery bypass grafting on chest
      pain during 2 years of follow-up after the operation and to identify predictors
      of chest pain and its relationship to myocardial ischaemia 2 years after the
      operation. METHODS: Patients were approached with a questionnaire at the time of
      coronary angiography (1291) and 3 months (1664), 1 year (1638) and 2 years (1613)
      after coronary artery bypass grafting. Two years after the operation, a
      computerised 12-lead electrocardiogram was obtained during a standardised bicycle
      exercise test (618). RESULTS: Prior to surgery, 37% of the patients were unable
      to perform physical activity compared with 6% after the operation (P < 0.0001 for
      change in degree of limitation). Only 3% had no chest pain at all prior to the
      operation, while 58% of the patients were free from chest pain 2 years after
      surgery (P < 0.0001). We found no correlation between patients reporting chest
      pain and signs of ischaemia at exercise test, but there was a highly significant
      correlation with chest pain during the exercise test (P < 0.0001). Independent
      predictors of chest pain were severity of preoperative angina (P < 0.0001),
      younger age (P = 0.0009), previous coronary artery bypass grafting (P = 0.003),
      duration of symptoms (P = 0.005), the need for prolonged cardiopulmonary bypass
      (P = 0.04) and the absence of left main stenosis (P = 0.04). CONCLUSION:
      Independent predictors of chest pain were identified 2 years after coronary
      artery bypass grafting. There was a dramatic improvement after coronary artery
      bypass grafting. However, almost half the patients complained of some kind of
      chest pain even after the operation. This chest pain correlated well with chest
      pain during the exercise test but not with signs of myocardial ischaemia.

PMID- 9288524
TI  - Coronary artery revascularization in an adult with coronary aneurysms probably
      secondary to childhood Kawasaki disease.
AB  - Kawasaki disease is an acute febrile illness affecting mainly infants and
      children. The fatal complication of Kawasaki disease is coronary involvement
      pertaining to coronary artery aneurysms. Surgical experience of adults that had
      childhood Kawasaki disease with coronary lesion has been rarely reported. We
      experienced coronary artery bypass grafting in a 44 year old man with no risk
      factors for atherosclerosis but with coronary lesions possibly secondary to
      Kawasaki disease. Coronary artery sequelae of Kawasaki disease may become part of
      a cause of coronary disease in young adults and we should recognize this
      condition in such patients with coronary disease but no coronary risk factors.

PMID- 9288525
TI  - Four-channeled aortic dissection and rupture.
AB  - A four-channeled aortic dissection is quite rare, which is a highly life
      threatening situation predisposing to aortic rupture. We report a successful
      management of a four-channeled aortic dissection and an aortic rupture in a 59
      year-old woman with Marfan's syndrome 11 years after an initial Bentall procedure
      for DeBakey type I dissection. The total arch and the descending thoracic aorta
      were replaced under deep hypothermia and circulatory arrest.

PMID- 9288526
TI  - Isolated primary chylopericardium.
AB  - Isolated primary chylopericardum is known to be a rare clinical entity. A 17-year
      old girl was diagnosed as isolated primary chylopericardium. She was unresponsive
      to conservative treatment with pericardial tube drainage and medium chain
      triglyceride diet. At 2 weeks after the conservative treatment, ligation and
      resection of the thoracic duct with establishment of a pericardial window through
      a left thoracotomy was performed. At 6 months, follow-up showed no accumulation
      of the pericardial fluid. This case also supports that ligation and resection of
      the thoracic duct with establishment of a pericardial window is the treatment of
      choice in isolated primary chylopericardium.

PMID- 9288527
TI  - Repair of anomalous connection of the left coronary artery to the pulmonary
      artery using native aortic and pulmonary tissue flaps.
AB  - A modified repair technique in anomalous connection of the left coronary artery
      to the main pulmonary artery is reported in which transfer of the origin of the
      vessel into the aortic root is facilitated by augmentation with native aortic and
      pulmonary tissue flaps. This modification reduces tension on the anastomosis and
      may enhance the likelihood of successful transfer of the left coronary artery
      into the aortic root.

PMID- 9288528
TI  - Aortic root replacement in type A dissection.

PMID- 9288529
TI  - Lung volume reduction for congenital lobar emphysema.

PMID- 9288530
TI  - Surgical approach for replacement of degenerated mitral bioprostheses.

PMID- 9288531
TI  - Relationships among microalbuminuria, insulin resistance and renal-cardiac
      complications in insulin dependent and non insulin dependent diabetes.
AB  - A rate of albumin excretion rate above 20 micrograms/min is a predicting factor
      of overt nephropathy in Type I diabetes. It has not yet been established whether
      this is the case also for Type II diabetes, where microalbuminuria is antecedent
      to general and cardiovascular mortality but not to end-stage renal disease. The
      reasons accounting for this discrepancy between Type I and Type II diabetes have
      not been fully elucidated. In principle two different hypotheses can be
      postulated to explain these findings. Firstly it can be suggested that overt
      proteinuria is not detected with similar incidence rates in microalbuminuric
      patients with the two types of diseases because Type II diabetics are older and
      more prone to develop cardiovascular events. Therefore these patients would die
      frequently before developing overt proteinuria not because microalbuminuria is
      not a predicting factor of End-stage Renal Disease, but rather because the follow
      up period is not long enough to monitor the patients till the very moment they
      develop renal complications. Alternatively it is possible that microalbuminuria
      reflect a systemic, endothelial and vascular disorder rather than glomerular
      structural abnormalities in these patients. We have recently described a
      clustering of clinical features encompassing microalbuminuria, hypertension,
      peripheral extrahepatic insulin resistance, renal and cardiac hypertrophy and
      altered cation membrane transport systems, not in the overall Type II diabetic
      population, but only in a cohort of these patients. Evidences in keeping with a
      strict association between insulin resistance, hypertension and microalbuminuria
      in a subgroup of Type II diabetic patients have been recently reported by several
      authors both in cross-sectional and longitudinal studies. However the hypothesis
      that microalbuminuria reflects a systemic endothelial and vascular disorder in
      Type II diabetic patients, does not rule out the possibility that these systemic
      disturbances are also associated with histologic abnormalities of the kidney.
      With regard to the characteristics of renal histology in Type II diabetic
      patients with and without microalbuminuria, preliminary data from our laboratory
      demonstrate that there is no evidence of any renal disorder other than diabetes
      in microalbuminuric Type II diabetic patients. More particularly in this subset
      of patients we observed typical features of diabetic nephropathology (glomerular,
      tubulo-interstitial and arteriolar changes), while a substantial number of
      patients with increased albumin excretion rate exhibited either marked tubulo
      interstitial lesions or arteriolar hyalinosis or both, in absence of significant
      glomerular changes. These findings suggest that it is not true that Type II
      diabetic patients with microalbuminuria show quite often normal renal histology,
      but rather than hyperglycemia may cause different patterns of renal injury as
      compared to Type I Diabetes. Furthermore always with regard to renal histology,
      it has been pointed out that in Type I diabetes glomerulopathy (especially
      mesangial) is the crucial change, whereas recent studies found considerable
      structural heterogeneity amongst proteinuric Type II diabetic patients with
      relatively high incidence of renal diseases other than diabetes. However parallel
      studies in a small group of micromacroalbuminuric Type II diabetic patients
      reported the typical glomerular changes, usually shown by Type I diabetic
      patients with similar patterns of renal damage. The issue of the relationships
      between microalbuminuria, hypertension and the development of overt nephropathy
      in Type II diabetes has been also examined in Pima Indians. The clinical scenario
      found in these patients does closely resemble that of Caucasian Type I diabetic
      patients.

PMID- 9288532
TI  - Circadian variations in blood pressure and heart rate in diabetes prone and
      resistant rat strains compared with spontaneously hypertensive rats.
AB  - Circadian blood pressure (BP), heart rate (HR) and motor activity (MA) of
      nondiabetic (nd) and spontaneously diabetic (d) BB/OK rats were compared with
      that of spontaneously hypertensive rats (SHR). In addition a diabetes-resistant
      and non-hypertensive rat strain (LEW.1W) was monitored for the same parameters.
      Systolic and diastolic BP (SBP, DBP), HR and MA were measured telemetrically. In
      d BB rats, the 24 h mean value of SBP (132 +/- 0.15 mm-Hg) was significantly
      increased compared to nd BB rats (125 +/- 0.18 mmHg). No differences were found
      in DBP between d and nd BB rats (93 +/- 0.13 v.s. 94 +/- 0.15 mmHg). Both, d and
      nd BB rats were significantly different in SBP and DBP to that of SHR (155 +/-
      0.19 and 110 +/- mmHg). Nondiabetic BB rats did not significantly differ from
      LEW.1W rats in SBP and DBP (125 vs. 123 mmHg and 94 vs. 94 mmHg). The heart rate
      was lowest in diabetic BB rats compared with all other strains. Compared to nd BB
      the diabetic rats had an altered daily rhythm in BP. The results demonstrate that
      the diabetic BB rats develop circadian variations in BP and HR similar to those
      observed in hypertensive rats.

PMID- 9288533
TI  - Neurovascular compression at the left ventrolateral medulla as an etiological
      factor for arterial hypertension.
AB  - Clinical studies by Jannetta and others implicated that arterial compression of
      the root entry zone (REZ) of cranial nerves IX and X at the left ventrolateral
      medulla may represent an etiological factor for arterial hypertension. Positive
      therapeutic outcomes with reduction of hypertension in 42 of Jannetta's patients
      by microsurgical decompression initiated further studies. Experience of our group
      points in the same direction. Four patients treated by microvascular
      decompression showed lasting reduction of severe hypertension postoperatively. In
      our previous comparing postmortem explorations and angiographic studies essential
      hypertensive patients displayed signs of left sided neurovascular compression in
      opposition to normotone controls or renal hypertensive patients. By using MR
      imaging we are currently developing a method of detecting neurovascular
      compression syndromes in hypertensive patients suitable for surgical management.

PMID- 9288534
TI  - Distal arterial occlusive disease in diabetes is related to medial arterial
      calcification.
AB  - In diabetes mellitus, peripheral arterial occlusive disease predominantly affects
      the lower leg (tibial and peroneal vessel disease). Our study suggests that this
      feature is related to the presence of forefoot medial arterial calcification.

PMID- 9288535
TI  - Sodium-hydrogen exchange isoform expression in blood cells: implications for
      studies in diabetes mellitus.
AB  - There have been many reports of increased Na-H exchange (NHE) activity in the
      peripheral blood cells (erythrocytes, lymphocytes and platelets) of patients with
      diabetes mellitus compared to nondiabetic controls. This raised NHE activity has
      been hypothesized to reflect increased NHE activity in kidney and vascular smooth
      muscle. Raised NHE activity in these tissues could play a pathophysiological role
      in mediating hypertension, vascular smooth muscle cell proliferation and
      progressive renal impairment. It is now known that there are at least five NHE
      isoforms, but a specific study examining expression of NHE isoforms in peripheral
      blood cells has not been reported. This study used specific antisera to NHE
      isoforms 1, 3 and 4 to examine NHE expression by immunoblot analysis.
      Erythrocyte, lymphocyte and platelet membranes from both rabbit and rat were
      separated by standard methods. A monoclonal antibody to NHE-1 reacted with a 100
      110 kDa band in rabbit and rat platelets and lymphocytes (identical to that
      observed in basolateral-enriched renal cortical vesicles) and a 100 kDa band in
      rabbit and rat erythrocytes. In both species, the intensity of the staining was
      greatest in platelet membranes. A polyclonal antibody to NHE-3, the isoform
      present on the apical membranes of renal proximal tubule, showed no evidence of
      staining in any of the peripheral blood cell preparations. Similarly there was no
      evidence of expression of NHE-4 in the peripheral blood cell preparations.
      Peripheral blood cells express NHE-1, which likely accounts for amiloride
      sensitive Na-H exchange in these cells, playing a role in cell volume and pH
      regulation. However, there is no evidence that there is expression of NHE-3 or
      NHE-4 in peripheral blood cells. These data have implications for studies in
      hypertension and diabetes mellitus which measure peripheral blood cell Na-H
      exchange and hypothesize regarding a direct pathophysiological role for this
      increased activity.

PMID- 9288536
TI  - Erythrocyte carbonic anhydrase activity in smokers and in diabetic patients.
AB  - Carbonic anhydrase activity was measured in lyzed erythrocytes from smoking and
      non-smoking young men as well as from diabetic and healthy young women. Enzyme
      activity was determined by a changing-pH-assay, using a stirred reaction vessel
      and glass pH electrode. CAA was lower in smokers than in non-smokers.
      Furthermore, it was lower in diabetics than in nondiabetic controls. We conclude
      that cigarette smoking as well as diabetes mellitus may reduce erythrocyte
      carbonic anhydrase activity.

PMID- 9288537
TI  - K(+)-permeability in diabetics and nondiabetics with and without renal
      insufficiency.
AB  - Looking for causes or consequences of primary hypertension much attention is
      drawn to the ion transport systems of the cellular membrane. The existence of
      endogeneous digitalis-like factors, that lower the activity of Na+/K(+)-ATPase
      and result in a complex change of electrolyte balance of cells are discussed as a
      reaction of the organism to salt and volume retention. The measurement of passive
      permeability of erythrocyte membranes for potassium is an easy and useful method
      for the detection of disturbances of Na+/K(+)-transport, especially for extensive
      screening investigations. We examined the potassium permeability of erythrocytes
      in healthy individuals (GR1, n = 48), patients with compensated renal
      insufficiency (GR2, n = 36) and diabetics (GR3, n = 25) as well as a group of
      diabetics with renal failure (GR4, n = 47). The relative change of potassium
      concentration in the whole blood, based on the efflux of potassium during a 4
      hour-incubation at 37 degrees C, is defined as a measure for K(+)-permeability.
      K(+)-concentrations are determined every 60 minutes with ion sensitive
      electrodes. K(+)-permeability was significantly increased in patients with
      compensated renal insufficiency compared to the control group and to diabetics.
      Diabetics differed markedly in their erythrocyte reaction regarding K(+)
      permeability. Whereas patients with renal insufficiency show an efflux of
      potassium during investigation there is a decrease of potassium in plasma in
      diabetics. The K(+)-permeability results of patients with both diseases are
      intermediate between the GR2- and GR3 results and are significantly different
      from the control group. When g-strophanthin is added to inhibit the sodium pump,
      the differences between the groups are abolished. The decreased K+permeability in
      diabetics compared to the control group could be explained by the increased
      supply of energy-rich substrates for the Na+/K(+)-ATPase.

PMID- 9288538
TI  - Salt sensitivity and insulin resistance in normotensives.
AB  - Among hypertensive patients salt sensitivity and insulin resistance are commonly
      observed together. We investigated if a causal relationship already exists in
      young normotensive adults. With a standardized dietary regimen we determined salt
      sensitivity in 35 male volunteers by measuring diastolic blood pressure (24-hours
      RR-recording). Insulin resistance was tested using hyperinsulinaemic-euglycaemic
      clamp-technique by de Fronzo after a freely chosen diet, after 7 days of salt
      loading (260 mmol/d) and after 7 days of salt restriction (60 mmol/d). Data from
      euglycaemic-clamp technique were available from 27 subjects. 18 of them (67%)
      could be characterized as salt resistant; 9 persons (33%) were salt sensitive.
      Glucose infusion rate, mean glucose and insulin concentrations were measured in
      plasma, metabolic clearance rate (MCR) and indices of insulin sensitivity (ISI)
      were calculated. The results of MCR and ISI show large interindividual variances.
      There were no differences between the salt sensitive and salt resistant group
      regarding the mean insulin concentrations and also the mean glucose uptake in the
      steady state clamp period and also the calculated MCR and ISI. Comparing the
      periods of different salt intake, there were no differences between salt loading
      and salt restriction. Whereas salt sensitivity can already be shown in the
      normotensive state, with this experimental design a changed insulin sensitivity
      is not detectable. This supports the idea, that insulin resistance is not
      causally linked with salt sensitivity. It may be a secondary phenomenon of salt
      induced hypertension.

PMID- 9288539
TI  - Cardiovascular and renal effects of systemic hypoxia in chronically instrumented
      conscious WKY and SHR rats.
AB  - The effects of systemic hypoxia upon cardiovascular and renal function in
      normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) are
      controversial. We examined the effects of systemic normobaric hypoxia (12.5% O2
      in N2 for 4 hours) on arterial blood gases (pO2, pCO2, pH), mean arterial
      pressure (MAP), heart rate (HR), effective renal blood flow (ERBF), glomerular
      filtration rate (GFR), urine flow (UMV) and renal sodium excretion (U Na V) in
      conscious unilaterally nephrectomized WKY (n = 12) and SHR (n = 14) chronically
      instrumented with an arterial, venous and ureter cannula. In WKY hypoxia caused a
      reduction in arterial pO2 and pCO2 but no change in MAP and HR. In SHR hypoxia
      induced similar reductions in arterial blood gases, a small decrease in MAP and
      no change in HR. In both strains hypoxia caused significant increases in ERBF,
      GFR and U Na V, but insignificant changes in UMV. The hypoxia-induced natriuresis
      developed 90-120 min after starting the hypoxia. These data indicate that a 4
      hour lasting hypoxia has profound effects on sodium excretion in conscious WKY as
      well as SHR. Systemic hypoxia did not cause significant changes in arterial blood
      pressure in both rat strains.

PMID- 9288540
TI  - The role of insulin and proinsulin in the regulation of triglyceride metabolism.
AB  - The mechanisms underlying the associations between abnormal glucose tolerance and
      myocardial infarction are poorly understood. It has often been suggested that an
      increased plasma insulin concentration is causally linked to many of the
      metabolic abnormalities that are associated with abnormal glucose tolerance,
      although this suggestion remains controversial. Recently it has been proposed
      that proinsulin and proinsulin-like molecules may also be involved in the
      atherogenic process. Both hyperinsulinaemia and insulin resistance are associated
      with fasting hypertriglyceridaemia and both increased VLDL production and
      increased plasma triglyceride concentrations commonly occur in association with
      abnormal glucose tolerance and atheromatous vascular disease. In order to study
      the effects of insulin, proinsulin and proinsulin-like molecules on hepatic
      triglyceride secretion we have undertaken experiments in vitro using the liver
      cell line HepG2. In conjunction with these in vitro experiments we have also
      studied, in vivo, the associations between insulin, proinsulin, proinsulin-like
      molecules and plasma triglyceride concentrations in subjects with both normal and
      abnormal glucose tolerance. Our results in vitro show that proinsulin and
      proinsulin-like molecules have similar and not different effects to insulin but
      are less biologically active. In vivo, our results show that concentrations of
      insulin, proinsulin and proinsulin-like molecules per se are not an important
      determinant of plasma triglyceride concentrations. Both abnormal NEFA suppression
      during an oral glucose tolerance test and increased central adiposity are closely
      linked to poor glucose tolerance and are the most important determinants of
      plasma triglyceride concentrations. Taken together these results suggest that it
      is not insulin nor proinsulin concentrations per se that are causally linked to
      hypertriglyceridaemia. We suggest that abnormal NEFA suppression plays an
      important part in the increase in risk of vascular disease associated with
      insulin resistance.

PMID- 9288541
TI  - Chylomicrons induce E-selectin and VCAM-1 expression in endothelial cells.
AB  - An increased adherence of leukocytes to the vascular endothelium appears to be a
      crucial event in the development of atherosclerosis. The role of endothelial cell
      adhesion molecules is gaining increasingly interest in this context. Several
      studies show an influence of lipoproteins, especially low-density-lipoproteins on
      adhesion molecule stimulation. The aim of our study was to analyze the
      atherogenic potential of postprandially elevated serum triglyceride levels by
      investigating the impact of postprandial lipoproteins (chylomicrons (CH, isolated
      4 h after a standard oral lipid load)) on the expression of E-selectin
      (endothelial leukocyte adhesion molecule-1, ELAM-1) and VCAM-1 (vascular cell
      adhesion molecule-1). In addition we used chylomicrons that had been incubated
      with lipoprotein lipase (50 U/ml) for 3 h (CH-LPL). The endotoxin
      lipopolysaccharide (LPS) served as positive control for adhesion molecule
      stimulation. Human umbilical vein endothelial cells (HUVEC) were incubated with
      the samples for 4 h and expression of E-Selectin and VCAM-1 was determined by
      ELISA. The expression of E-selectin was induced by LPS (530 +/- 64% compared to
      the basal activity (= 100%)) and by CH (342 +/- 94%); CH-LPL had no effect on E
      Selectin expression. VCAM-1 expression was stimulated by LPS (395 +/- 221%) and
      similarly by CH-LPL (322 +/- 136%) but considerably stronger by CH (1245 +/-
      324). In summary, chylomicrons induced an enhancement of the expression of both
      adhesion molecules, which closely resembled or even exceeded the endotoxin
      induced stimulation. Interestingly, this effect was diminished or even reversed
      after incubation with LPL.

PMID- 9288542
TI  - Circulating endothelin-1 levels in obese patients with the metabolic syndrome.
AB  - We evaluated venous plasma ET-1 concentrations in 18 never-treated obese men
      (body mass index 31.0 +/- 0.5 kg/m2; age 45.4 +/- 4.3 years) showing the whole
      features of the above syndrome and 12 control men (age 44.1 +/- 3.6 years).
      Circulating ET-1 levels were significantly higher in patients than in controls (p
      < 0.05), and were directly correlated with fasting insulin levels (r = 0.564, p =
      0.015) and erythrocyte Na+/Li+ counter-transport activity (r = 0.504, p = 0.033).
      In conclusion, venous plasma ET-1 levels are elevated in obese men manifesting
      the whole features of the metabolic syndrome. Due to the biological properties of
      ET-1, our findings suggest the peptide as a further component of the cluster of
      cardiovascular risk factors which characterizes this syndrome.

PMID- 9288544
TI  - Hyper- and hypoinsulinemia in type-2 diabetes: what may be wrong in the secretory
      mechanism of the B-cell.
AB  - Type-2 diabetes frequently is the consequence of overnutrition causing
      overweight, which then produces insulin resistance. The following hyperglycemia
      induces permanent overstimulation of the insulin secretory machinery of the B
      cell, which results in hyperinsulinemia and/or hypoinsulinemia. The mechanisms,
      however, of these disturbances are not understood so far. Animal models, which
      can be used to solve these questions, are, among others, long-term incubation of
      pancreatic islets in culture in the presence of high glucose and/or long-term
      infusion of rats with glucose. Using these models sensitization [Bedoya and
      Jeanrenaud, 1991; Leahy et al., 1987; Purrello et al., 1992; Thams, 1991;
      Thibault et al., 1993; Timmers et al., 1990] and/or desensitization of insulin
      release [Bedoya and Jeanrenaud, 1991; Leahy et al., 1987; Davalli et al., 1992;
      Eizirik et al., 1992; Bolaffi et al., 1988; Timmers et al., 1990] have been
      reported. Whether or not there is sensitization or desensitization depends on the
      glucose concentration [Eizirik et al., 1992; Leahy et al., 1986; Sako and Grill,
      1990] and the duration of glucose action [Bedoya and Jeanrenaud, 1991; Bolaffi et
      al., 1988]. Both, sensitization and desensitization, appear to be reversible on
      return to normal glucose or mild hypoglycemia [Leahy and Weir, 1991; Svenson and
      Hellerstrom, 1991]. It seems, however, that there is a fluent change from the
      first occurring hyperinsulinemia to hypoinsulinemia. In this lecture I first want
      to talk about the possible mechanism of sensitization of insulin secretion
      discussing previous results we have obtained from rat islets isolated after a 48
      hours period of i.v. infusion with 50% glucose. In the second part I will discuss
      some of the findings coming from the respective literature concerning
      desensitization of insulin secretion.

PMID- 9288543
TI  - Increased levels of plasma endothelin-1 in non-insulin dependent diabetic
      patients with retinopathy but without other diabetes-related organ damage.
AB  - Increased levels of endothelin (ET-1), a potent endothelium-derived
      vasoconstrictive peptide, have been found in plasma from non-insulin dependent
      diabetic (NIDDM) patients, suggesting that ET-1 might represent a new marker of
      diabetes-related vascular damage. To elucidate this topic, circulating ET-1
      levels were evaluated in 16 NIDDM patients in good metabolic control without
      either cardiovascular risk factors (obesity, hypertension, smoking,
      hyperdislipidaemia, etc.) or diabetes-related damage of other districts and in 12
      healthy subjects. Retinopathy was assessed by ophthalmological evaluation and its
      severity determined by Klein criteria. Resulting data showed higher levels of
      plasma ET-1 in NIDDM patients than in control subjects (0.80 +/- 0.13 vs 0.60 +/-
      0.12 pg/mL, p < 0.001). Plasma ET-1 levels were directly correlated with
      retinopathy degrees in NIDDM patients affected by retinopathy (n = 10; r = 0.368;
      p = 0.02), and were significantly higher in these latter (n = 10) than in those
      without retinopathy (n = 6) (0.89 +/- 0.13 vs 0.71 +/- 0.19 pg/mL, p < 0.05). The
      increased levels of ET-1 could contribute to retinopathy development or, more
      probably, represent a marker of this diabetes-related complication.

PMID- 9288545
TI  - Functional alterations in the rat kidney induced either by diabetes or high
      protein diet.
AB  - The aim of this study was to compare the effect of long-term diabetes with that
      of a long-term high protein diet in vivo on the kidney function and in vitro on
      cellular parameters of isolated glomeruli of BB rats. Four groups of rats were
      investigated: Group 1 = normoglycaemic (N) rats > 250 days old; group 2 = age
      matched diabetic (D) rats with a diabetes duration of more than 150 days; group 3
      = BB rats which were fed a protein diet of 8% (low protein = LP) and group 4 =
      rats which received a high protein (HP) diet (32%) for more than 80 weeks. From
      24-h-urine samples albumin, urea, creatinine and electrolyte excretion were
      estimated. At the end of the study the total kidney weight was determined and
      glomeruli were isolated for in vitro experiments. Hyperglycaemic and HP fed rats
      were characterised by a significantly increased excretion of albumin, urea and
      different electrolytes compared to normoglycaemic or LP fed animals. Creatinine
      excretion was neither affected by hyperglycaemia nor HP diet. HP and D caused a
      significant increase in total kidney weight when compared to the LP and N group,
      respectively (N: 1.79 +/- 0.08; D: 2.33 +/- 0.09; LP: 2.26 +/- 0.18; HP: 3.28 +/-
      0.46 g; p < 0.05). The increased kidney weight of diabetic and HP rats correlated
      well with a significant enhanced DNA content of isolated glomeruli (N: 3.41 +/-
      0.15; D: 4.45 +/- 0.19; LP: 4.18 +/- 0.35; HP: 6.40 +/- 0.62 micrograms/1000
      glomeruli; p < 0.02). In addition, glomeruli obtained from either D or HP fed BB
      rats incorporated significantly more 3H-thymidine into their DNA indicating an
      elevated rate of DNA synthesis. The results demonstrate that HP diet caused
      markedly altered kidney function and induced cellular changes of glomeruli which
      are interpreted as enhanced proliferative processes. These alterations are
      comparable to those associated with diabetes mellitus. An unbalanced high protein
      diet represents a considerable risk factor for the development of functional and
      structural impairments of the kidney and should absolutely be avoided in patients
      suffering from diseases which are known to be associated with kidney alterations.

PMID- 9288547
TI  - The metabolic syndrome: from inherited survival trait to a health care problem.
AB  - A critical role is proposed for the quantity and quality of dietary carbohydrate
      in the pathogenesis of the insulin resistance and hyperinsulinaemia which
      characterise the Metabolic Syndrome. We propose that an insulin-resistant
      genotype evolved to provide survival and reproductive advantages for the cold
      climate, large game hunters of the last Ice Age who consumed a low carbohydrate,
      high protein diet with periodic starvation. Insulin resistance would have
      minimised glucose utilisation by muscles thereby facilitating the preferential
      utilisation of glucose by the brain, foetus and mammary gland. But beginning
      about 10,000 years ago following the end of the last Ice Age and the development
      of agriculture, dietary carbohydrate increased and the selection pressure for
      insulin resistance decreased in some groups. Agriculture began in the Middle East
      and spread throughout Europe long before it was developed elsewhere. Hence the
      prevalence of the insulin-resistant genotype decreased in Europeans and other
      groups exposed to a high carbohydrate intake for sufficiently long. Some
      geographically isolated groups such as the Pima Indians and Nauruans experienced
      conditions which further diminished the gene pool diversity and resulted in
      particularly insulin resistant populations. Traditional carbohydrate foods have a
      low glycaemic index and produce only modest increases in plasma insulin. However,
      the constant supply of highly refined high glycaemic index carbohydrate in modern
      diets, results in postprandial hyperinsulinaemia. The insulin-resistant genotype
      is now disadvantageous and predisposes to the development of the Metabolic
      Syndrome.

PMID- 9288546
TI  - Increased prevalence of elevated urinary albumin excretion rate in type 2
      diabetic patients suffering from ischemic foot lesions.
AB  - Present cross-sectional clinical study was aimed at the evaluation the prevalence
      of cardiovascular risk factors in Type 2-diabetics suffering from different
      clinical manifestations of diabetic foot lesions due to peripheral vascular
      disease and/or diabetic neuropathy. 1025 non-insulin-dependent (Type 2) diabetics
      (NIDDM) of both sexes were investigated. Patients were classified in Type II
      diabetes without peripheral vascular disease and foot lesions (group 0,
      controls), with macroangiopathic related foot lesions (group 2), with neuropathic
      foot lesions (group 3), and with mixed neuropathic-ischemic foot lesions (group
      4). Apart from urinary albumin excretion rate (UAE), the following micro- and
      macroangiopathic risk factors and diseases were taken into account: Hypertension,
      degree of metabolic control (HbA1c), lipid concentrations, duration of diabetes,
      retinopathy, clinical nephropathy. RESULTS: In the total population the UAE was
      significantly (p < 0.01) correlated with duration of diabetes, serum creatinine,
      hypertension, age, lipid concentrations, HbA1c and insulin requirement. In
      comparison to Type II diabetic patients without peripheral vascular disease
      (group 0) and with neuropathic foot lesions (group 3), subjects with ischemic
      (group 2) and mixed neuropathic-ischemic foot lesions demonstrated an increased
      prevalence of pathological UAE, which was associated with a higher frequency of
      clinical nephropathy, retinopathy, an older age and longer duration of diabetes.
      It is concluded that microalbuminuria in Type 2 diabetes reflects both the
      existence of diabetic nephropathy and peripheral vascular disease which is often
      associated with the insulin resistance syndrome.

PMID- 9288548
TI  - Cellular protective action of angiotensin converting enzyme inhibitors.
AB  - In several studies organ protective effects of ACE inhibitors independent from
      their antihypertensive action have been demonstrated. The mechanisms of the
      protective effects of angiotensin converting enzyme (ACE) inhibitors on
      vasculature and kidney are largely unknown. In the present study the modulatory
      action of captopril on the angiotensin II (AngII), arginine vasopressin (AVP),
      and platelet derived growth factor (PDGF)-induced increase of cytosolic free
      calcium concentration ([Ca2+]i) was investigated in cultured vascular smooth
      muscle cells (VSMC) and cultured glomerular mesangial cells (MC) from rats using
      the fluorescent dye technique. Resting [Ca2+]i in VSMC or MC was not
      significantly affected by captopril. The preincubation of VSMC with 1 mumol/l
      captopril significantly reduced the AngII-induced [Ca2+]i increase in VSMC from
      90 +/- 10 nmol/l (n = 78; mean +/- SEM) to 51 +/- 16 nmol/l (n = 53; p < 0.05)
      and in MC from 102 +/- 42 nmol/l (n = 14) to 43 +/- 12 nmol/l (n = 7; p < 0.05).
      In the absence of extracellular calcium captopril produced no effect on AngII
      induced changes of [Ca2+]i. Captopril significantly attenuated the AVP-induced
      [Ca2+]i increase in VSMC and MC. The preincubation of MC with 1 mumol/l captopril
      for 40 min significantly reduced the PDGF-induced [Ca2+]i increase in MC from 127
      +/- 31 nmol/l (n = 11) to 61 +/- 32 nmol/l (n = 5, p < 0.05). The present results
      may indicate that part of the protective effects of ACE inhibitors on vasculature
      and kidney may be promoted by inhibition of growth-factor induced changes of
      calcium homeostasis.

PMID- 9288549
TI  - New drugs and clinical trials in diabetes and hypertension.
AB  - Hypertension is a well-established risk factor for cerebro-cardiovascular disease
      in diabetics, as well as for progressing renal disease. Several
      pathophysiological mechanisms link hypertension with non-insulin-dependent
      diabetes (NIDDM), e.g. insulin resistance. This will be discussed below as
      regards pathophysiology and treatment possibilities, especially with new drugs in
      ongoing clinical trials.

PMID- 9288550
TI  - Complementary insulin therapy improves blood glucose and serum lipid parameters
      in type 2 (non-insulin-dependent) diabetic patients. I. Effects on blood glucose
      control.
AB  - Aim of the present prospective study was to assess the potential benefits of
      complementary insulin therapy, consisting of a single dose of 1 to 8 units of
      shortacting insulin before each meal, on blood glucose, serum lipid parameters
      and on patient's well-being. A group of 251 type 2 (non-insulin-dependent)
      diabetic patients completed the study. The complementary insulin therapy was
      introduced in hospital in the course of one week. Number of injections per day
      was increased, the average dose of insulin per day and the average dose of
      glibenclamide decreased, amount of carbohydrates in food (adapted by patients
      themselves) diminished, mean blood glucose, number of hyperglycaemia's and number
      of hypoglycaemia's decreased. At a check-up 8 to 10 weeks later, a decrease of
      haemoglobin A1c, glycated proteins in serum and body mass index together with
      improved patient's well-being have been shown. These results demonstrate a good
      effectiveness of complementary insulin therapy in type 2 (non-insulin-dependent)
      diabetic patients. We assume this kind of therapy should be more often
      recommended.

PMID- 9288551
TI  - Complementary insulin therapy improves blood glucose and serum lipid parameters
      in type 2 (non-insulin-dependent) diabetic patients. II. Effects on serum lipids,
      lipoproteins and apoproteins.
AB  - The aim of the present study was to evaluate the effects of complementary insulin
      therapy, consisting of a single dose of 1 to 8 units of shortacting insulin
      before each meal (4-6x daily) and sometimes at 02.30 h, on concentrations of
      serum lipids, lipoproteins and apoproteins in type 2 (non-insulin-dependent)
      diabetic patients, unsatisfactorily controlled either by oral hypoglycemic agents
      (OHA) or by longacting insulin 1-2x daily (INS 1-2). Compared means +/- SD.
      Patients on INS 1-2 (n = 82) had better baseline glycemic control than patients
      on OHA (n = 68) (HbAlc: 9.33 +/- 1.76% vs. 10.59 +/- 1.83%, p < 0.001 and
      fructosamine: 3.34 +/- 0.74 mmol/l vs. 3.85 +/- 0.84 mmol/l, p < 0.001) and serum
      triglyceride concentrations (3.03 +/- 2.05 mmol/l vs. 4.95 +/- 4.48 mmol/l, p <
      0.001), in spite of longer duration of diabetes (13.35 +/- 8.07 years vs. 10.1 +/
      6.9 years, p < 0.001). After 8-10 weeks of complementary insulin therapy, OHA
      patients (n = 33) improved both the glycemic control (HbA1c: 10.5 +/- 1.78% vs.
      9.0 +/- 1.75%, p < 0.001) and fructosamine: 4.0 +/- 0.85 mmol/l vs. 3.5 +/- 0.76
      mmol/l, p < 0.001) and most of the lipid parameters (decreased serum
      triglyceride: 5.8 +/- 5.64 mmol/l vs. 3.6 +/- 4.69 mmol/l, p < 0.001, total
      cholesterol/HDL-cholesterol: 6.8 +/- 3.13 vs. 5.6 +/- 2.23, p < 0.01 and
      increased HDL-cholesterol: 1.0 +/- 0.30 mmol/l vs. 1.2 +/- 0.30 mmol/l, p <
      0.001, apo AI: 1.6 +/- 0.26 g/l vs. 1.8 +/- 0.28 g/l, p < 0.001, LpAI particles:
      0.6 +/- 0.1 g/l vs. 0.7 +/- 0.12 g/l, p < 0.001 and LDL-cholesterol/apo B: 2.1 +/
      0.67 vs. 2.7 +/- 0.67, p < 0.001). In patients previously on INS 1-2x (n = 34),
      complementary insulin therapy with reduced dose of insulin per day (49.6 +/- 22.5
      U/d vs. 36.6 +/- 13.3 U/d, p < 0.001) did not further improve glycemic control
      but improved the number of proatherogenic and antiatherogenic lipoprotein
      particles (decreased apo B: 1.7 +/- 0.52 g/l vs. 1.5 +/- 0.94 g/l, p < 0.01, apo
      AI/Lp AI: 2.9 +/- 1.01 vs. 2.3 +/- 0.98, p < 0.01 and increased Lp AI particles:
      0.6 +/- 0.10 g/l vs. 0.7 +/- 0.12 g/l, p < 0.0001); BMI also decreased (29.4 +/-
      4.28 kg/m2 vs. 28.9 +/- 4.24 kg/m2, p < 0.05). These results demonstrate that
      complementary insulin therapy probably induces antiatherogenic lipoprotein
      changes in NIDDM patients previously treated by either OHA or INS 1-2x. Thus,
      this type of therapy should be used more often and start earlier, and should be
      preferred to longacting insulins.

PMID- 9288552
TI  - Palmitic acid but not stearic acid inhibits NO-production in endothelial cells.
AB  - Several studies showed a diminished production of the endothelium-derived
      relaxing factor nitric oxide (NO) in the early stage of atherosclerosis. The
      inhibition of NO-production seems to be mediated by lipoproteins, especially
      oxidized low-density lipoproteins (ox-LDL). There is some evidence, that the
      interactions of lipoproteins and NO are associated with the phospholipid fraction
      of lipoproteins. Since fatty acids have different atherogenic properties
      depending on chain length, degree of saturation and steric configuration-, we
      investigated the effect of fatty acids on endothelial NO-production. Human
      umbilical vein endothelial cells were incubated with palmitic acid and stearic
      acid in different concentrations in culture medium enriched with serum albumin
      for five hours. After that, NO-production was stimulated by calcium-ionophore
      A23187. NO-production was determined by a bioassay method using RFL-6 cells
      followed by radioimmunological determination of cGMP. NO-production stimulated by
      calcium-ionophore A23187(100%) was decreased by palmitic acid (10, 50, 100
      microM) to 79 +/- 12%; 63 +/- 10% and 53 +/- 14%. In contrast, incubation with
      stearic acid (10, 50 and 100 microM) had no effect on A23187-stimulated NO
      production (94 +/- 11%; 93 +/- 11%; 104 +/- 15%). Thus, palmitic acid but not
      stearic acid dose-dependently inhibited NO-release by endothelial cells. These
      different actions parallel the differing atherogenic potential of the two fatty
      acids.

PMID- 9288553
TI  - Nephropathy in type II diabetes.
AB  - The incidence and prevalence of endstage renal failure from renal involvement in
      patients with type II diabetes has recently increased in the Western world and in
      Asia. Interesting differences of prevalence are found between different nations.
      The reasons for the recent increase in the frequency of nephropathy in type II
      diabetes include (i) an increasing prevalence of type II diabetes, (ii) aging of
      the population and (iii) improved survival of patients with type II diabetes.
      Today patients more frequently live long enough to experience diabetic
      nephropathy. In contrast to previous opinion, no major differences with respect
      to renal involvement are found between type I and type II diabetes. This concerns
      renal hemodynamics as well as renal histology, although non-specific changes
      presumably of an ischemic nature are more frequently found in patients with type
      II diabetes. The renal risk appears to be similar in type II diabetes, i.e.
      cumulative prevalence of proteinuria and the same is true for the rate of
      progression to renal failure.

PMID- 9288554
TI  - Differences in sarcoplasmic reticulum gene expression in myocardium from patients
      undergoing cardiac surgery. Quantification of steady-state levels of messenger
      RNA using the reverse transcription-polymerase chain reaction.
AB  - Little is known about any alterations in sarcoplasmic reticulum (SR) gene
      expression associated with cardiac diseases of varying degrees of severity. We
      assessed, using the reverse transcription-polymerase chain reaction (RT-PCR)
      technique, SR Ca2+ transport protein gene expression in small tissue samples from
      failing hearts in patients undergoing cardiac surgery. Total RNA was extracted
      from 30- to 50-mg samples from the hearts of 13 patients with coronary artery
      disease, congenital heart disease, or valvular heart disease. We used RT-PCR to
      synthesize and amplify cDNA encoding cardiac SR Ca(2+)-ATPase, ryanodine receptor
      (RYR), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The amount of each
      mRNA in the sample was expressed relative to the amount of GAPDH mRNA. The
      expression level of each mRNA was correlated with the cardiac functional index.
      The mRNA levels for Ca(2+)-ATPase and RYR varied between heart samples, but
      showed a positive correlation with left ventricular ejection fraction. Ca(2+)
      ATPase mRNA levels showed in inverse relationship with plasma brain natriuretic
      peptide. In addition, we isolated partial cDNA encoding a human cardiac RYR. The
      cDNA consisted of 487 nucleotides, and the nucleotide and deduced amino acid
      sequences showed 93% and 99% homology, respectively, to those of rabbit cardiac
      RYR. These results suggest that decreased levels of mRNA for SR Ca2+ transport
      protein could be related to abnormal cardiac function, regardless of the etiology
      of the heart disease. RT-PCR provides a rapid and economical way of quantifying
      the expression of multiple genes in small specimens and may, therefore, aid
      understanding of the pathophysiology and treatment of heart disease.

PMID- 9288555
TI  - Attenuated inhibition of adrenergic contraction by nitric oxide in injured guinea
      pig femoral artery.
AB  - The present study aimed to examine the altered modulation of adrenergic
      contraction by nitric oxide and sensory neuropeptides in balloon-injured muscular
      artery. A guinea pig femoral artery (GPFA) was injured by a newly developed
      silastic microballoon catheter. The contralateral GPFA served as the control. The
      studied GPFAs consisted of six groups; control (C) and injured (I) GPFA, isolated
      at 0 days, and 2 and 8 weeks after injury (C0, I0, C2, I2, C8, and I8). Isometric
      tension was measured in the presence of indomethacin (10(-5) M), to exclude
      effects of cyclooxygenase-generated eicosanoids. Endothelial removal with the
      catheter was confirmed by histological examination. In each group, except for 10,
      NG-nitro-I-arginine methyl ester (L-NAME, 10(-6) M) induced significant
      augmentation of perivascular nerve stimulation (PNS)-evoked adrenergic
      contraction, which was blocked by L-arginine (3 x 10(-4) M). The degree of L-NAME
      augmentation in I8 was significantly smaller than that in C8 and I2. Capsaicin
      (10(-6) M) did not significantly affect PNS-contraction in any group, indicating
      that there was no sensory neuropeptide involvement in this contraction. In I8,
      acetylcholine (10(-6) M)-induced relaxation after noradrenaline (10(-5) M)
      precontraction was significantly smaller than that seen in the other groups,
      except for I0, which was lacking in acetylcholine-induced relaxation.
      Histologically, injured GPFAs showed progressive intimal thickening. The present
      findings thus showed attenuated nitric oxide-mediated inhibition of adrenergic
      contraction, accompanying intimal thickening, in balloon-injured muscular artery,
      8 weeks after injury.

PMID- 9288556
TI  - Nipradilol, a new beta-adrenergic blocker, reduces left ventricular remodeling
      following myocardial infarction in spontaneously hypertensive rats.
AB  - Left ventricular (LV) cavity dilation (remodeling) following myocardial
      infarction (MI) is a risk factor for morbidity and mortality. This study was
      undertaken to determine whether nipradilol, a new beta-adrenergic blocker with
      vasodilating action, reduces LV remodeling after MI produced by coronary ligation
      in spontaneously hypertensive rats. The effects on LV remodeling of the following
      drugs, which were administered orally for 4 weeks, were evaluated by assessing LV
      end-diastolic volume index (LVEDVI): (1) vehicle, (2) nipradilol, 10 mg/kg per
      day. (3) propranolol, 50 mg/kg per day, and (4) captopril, 30 mg/kg per day.
      Since LVEDVI depends on infarct size, the effects of the drugs on LVEDVI were
      compared between rats with a similar infarct size, i.e., moderate, 20%-40%; and
      large, 40%-60%, on the basis of the histological determination of infarct size.
      The nipradilol-treated and captopril-treated rats had significantly smaller
      LVEDVI than did the vehicle-treated rats with both moderate and large infarction
      (large infarct: 2.48 +/- 0.12 ml/kg for the vehicle group, 1.69 +/- 0.10 ml/kg
      for the nipradilol group, P < 0.01, and 1.79 +/- 0.14 ml/kg for the captopril
      group, P < 0.01). In contrast, LVEDVI-in the propranolol-treated rats was
      significantly greater than that in the vehicle-treated rats with a moderate
      infarct (2.09 +/- 0.09 ml/kg for the vehicle group versus 2.44 +/- 0.10 ml/kg for
      the propranolol group, P < 0.05). The results indicate that nipradilol and
      captopril reduce LV remodeling after MI, whereas propranolol promotes it.

PMID- 9288557
TI  - QTc and not QTc dispersion behavior affects the occurrence of ventricular
      extrasystole during exercise in infarcted patients.
AB  - Both a long QTc and a large QTc dispersion (QTcd) can predispose infarcted
      patients to ventricular arrhythmias. The former simply reflects a general
      prolongation of ventricular recovery time, whereas QTcd is useful for revealing
      regional inhomogeneities of ventricular repolarization. The aim of our study was
      to evaluate QTc and QTcd behavior during exercise in 50 patients (all men) with
      previous myocardial infarction, and its possible correlation with the occurrence
      of exercise-induced premature ventricular complexes (EIPVC). Our patients
      underwent ergometric stress test with a load increase of 25 W, every 2 min, until
      the maximal age-related heart rate or symptoms were obtained, followed by a 10
      min recovery phase. QTc and QTcd measurement was performed at rest (BS) and
      during exercise at two progressively increasing heart rate steps: 100-115
      beats/min (T1) and 116-130 beats/ min (T2). The patients were divided into two
      groups according to the absence (group A; n = 22) or presence (group B; n = 28)
      of EIPVC. In terms of QTcd, no significant difference was found between the two
      groups at BS, T1, and T2. As for the mean QTc (QTcm), it was significantly longer
      in group B at BS (416 +/- 22 ms versus 395 +/- 19 ms; P = 0.001) and at T1 (431
      +/- 24 ms versus 410 +/- 8 ms; P = 0.0001). When group B was further
      differentiated into two subgroups-Bx and Bz-according to the severity of EIPVC,
      we noted that patients with the most severe arrhythmic response (group Bz; n =
      12) showed a persisting, significantly longer QTcm than group A (BS, 426 +/- 28
      ms versus 395 +/- 19 ms; P < 0.05; T1, 445 +/- 24 ms versus 410 +/- 8 ms; P <
      0.05; T2, 427 +/- 17 ms versus 412 +/- 14 ms; P < 0.05), and group Bx (n = 16)
      (BS, 426 +/- 28 ms versus 409 +/- 15 ms; P < 0.05; T1, 445 +/- 24 ms versus 420
      +/- 19 ms; P < 0.05; T2, 427 +/- 17 ms versus 410 +/- 17 ms; P < 0.05). Group Bx
      showed a significantly longer QTcm than group A only at BS (409 +/- 15 ms versus
      395 +/- 19 ms; P < 0.05). No significant difference in QTcd was found between the
      three groups at BS, T1, and T2. We also noted that the relationship between QTcm
      and QTcd was modified by the exercise, changing from a trend of direct relation
      at BS, towards an inverse one during effort, which reached significance at T2 (r
      = -0.319; P = 0.037). Based on our data, EIPVC occurrence seems to be more
      affected by the total duration rather than by regional inhomogeneities of the
      ventricular recovery time. In those patients with the most severe arrhythmic
      response, the autonomic modifications generated by the exercise succeed in
      attenuating only the regional inhomogeneities, but do not eliminate the
      differences in total duration of the repolarization period.

PMID- 9288558
TI  - Simultaneous evaluation of left- and right-sided heart pumping function during
      dynamic leg exercise in patients with mild chronic congestive heart failure, with
      special reference to afterload and plasma noradrenaline.
AB  - We simultaneously measured increases in mean pulmonary capillary wedge pressure
      (delta PCW), mean right atrial pressure (delta RA), and cardiac index (delta CI)
      in response to dynamic leg exercise in 81 patients with mild congestive heart
      failure to clarify the relationship between the left-sided and right-sided
      pumping function of the heart. The ratio of delta CI to delta PCW was used as an
      index of left-sided heart performance and the delta CI/delta RA as an index of
      right-sided heart performance. We also determined systemic vascular resistance,
      as an index of afterload on the left heart; pulmonary vascular resistance, as an
      index of afterload on the right heart; and the plasma level of noradrenaline
      before and during dynamic leg exercise. Patients with delta CI/delta PCW > 0.181/
      min/m2 per mmHg were regarded as having a well functioning left heart, and the
      patients with delta CI/delta PCW < or = 0.181/min/m2 per mmHg as having a poorly
      functioning left heart. Patients with delta CI/delta RA > 0.3111/min/m2 per mmHg
      were regarded as having a well functioning right heart, and those with delta
      CI/delta RA < or = 0.311/l/min/m2 per mmHg as having a poorly functioning right
      heart. Patients were classified into three groups: well functioning left and
      right heart (normal group; n = 40), poorly functioning left and right heart
      (bilateral group; n = 34), and poorly functioning left heart and well functioning
      right heart (left-sided group; n = 7). The systemic vascular resistance index
      decreased during leg exercise in all patients. The decrease was smaller in the
      bilateral group and the left-sided group than in the normal group. The pulmonary
      vascular resistance index increased during exercise in the bilateral group but
      was unchanged in the normal group and the left-sided group. The plasma level of
      noradrenaline increased during exercise in all patients, but the increase was
      greater in the bilateral and left-sided groups than in the normal group.
      Pretreatment with phentolamine, an alpha-adrenoceptor antagonist, inhibited the
      increase in the pulmonary vascular resistance index and restored the decrease in
      the systemic vascular resistance index during exercise in the bilateral group.
      Our results showed that systemic vascular resistance, which represents afterload
      on the left heart, increased in the presence of impaired left-sided heart pumping
      function and pulmonary vascular resistance, which represents afterload on the
      right heart, increased in the presence of impaired right-sided heart pumping
      function. The inhibited decrease in systemic vascular resistance and the increase
      in pulmonary vascular resistance during exercise were associated with alpha
      adrenoceptor-mediated vasoconstriction caused by the increase in the plasma level
      of noradrenaline.

PMID- 9288559
TI  - Evolution to dilated cardiomyopathy from acute eosinophilic pancarditis in Churg
      Strauss syndrome.
AB  - We describe the clinical manifestations of a patient with Churg-Strauss syndrome
      who presented with severe acute cardiac involvement and whose disease evolved to
      dilated cardiomyopathy (DCM), with special reference to the histopathological
      findings. Endomyocardial biopsies, conducted sequentially, three times within 10
      months, revealed severe eosinophilic endomyocarditis in the acute phase,
      interstitial fibrosis in the subacute phase, and endocardial thickening with
      mural thrombi, at 10 months. Although acute inflammation associated with
      elevation of eosinophil granule proteins subsided with steroid therapy, left
      ventricular dilatation with reduced contractility progressed. A subgroup of DCM
      is not considered to be idiopathic but, rather, an aftereffect of
      hypereosinophilic heart disease.

PMID- 9288560
TI  - Combined use of detachable coil against persistent mechanical hemolysis after
      transcatheter occlusion using Rashkind umbrella device in adult patient with
      patent ductus arteriosus.
AB  - Mechanical hemolysis after transcatheter occlusion of the patent ductus
      arteriosus using the Rashkind umbrella device has been postulated as a rare, but
      serious complication, even necessitating surgical repair. A rare, case of an
      adult patient with massive hemolytic anemia, successfully controlled by the
      combined use of several detachable coil devices is reported. The use of coil
      devices might be considered as a therapeutic option in such cases.

PMID- 9288562
TI  - Diabetes mellitus--new and noninvasive techniques for the study of metabolism.

PMID- 9288561
TI  - The epidemic of NIDDM in Asian and Pacific Island populations: prevalence and
      risk factors.

PMID- 9288563
TI  - Stable isotope techniques for the study of gluconeogenesis in man.
AB  - Glucose is produced by gluconeogenesis from pyruvate and its precursors and from
      glycerol and by glycogenolysis (Fig.1). We introduced a technique using 2H2O to
      quantitate the contribution of gluconeogenesis to glucose production in the
      fasted state (1,2). The method removes the uncertainty in older methods using
      radioactive or stable isotopes of knowing 1) the enrichment or specific activity
      of the gluconeogenic precursor being traced, 2) the contribution to
      gluconeogenesis of that precursor compared to contributions by the other
      precursors, and 3) the extent of dilution of label of that precursor in the Krebs
      cycle during the course of its conversion to glucose.

PMID- 9288564
TI  - Applications of PET in diabetes research.
AB  - Use of positron emission tomography (PET) combined with 18F-fluoro-2-deoxy-D
      glucose (18FDG) allows a noninvasive quantitation of glucose uptake in individual
      tissues such as human muscles and heart. Using 15O-labelled water and 18FDG the
      role of blood flow as a regulator of glucose metabolism can be studied with PET.
      PET has allowed study of the factors regulating heart glucose uptake in normal
      subjects and in subjects with alterations in skeletal muscle insulin sensitivity,
      and has provided evidence that insulin stimulated rates of blood flow and glucose
      uptake do not co-localize within muscle tissues.

PMID- 9288565
TI  - NMR and stable isotope techniques for studies of liver metabolism in man.
AB  - The pivotal role of the liver for glucose homeostasis resides within its ability
      to store large amounts of glucose in the form of glycogen, but also to rapidly
      release glucose into the circulation (1,2). Despite extensive studies on liver
      glycogen metabolism in vitro, studies in humans were limited to measurements of
      glycogen content by biopsy (3) before the introduction of in vivo 13C NMR
      spectroscopy for monitoring of hepatic glycogen in man (4).

PMID- 9288566
TI  - Microdialysis in adipose tissue and skeletal muscle.
AB  - Traditionally, investigation of metabolism in peripheral tissues such as the
      adipose tissue and muscles has been done by indirect measurements on whole body
      metabolism or in cannulated limbs. The microdialysis technique (1) was first
      invented and further developed (2) by neurobiologists for regional measurements
      in the rat brain. During the last ten years the technique has been used in
      several other organs in laboratory animals and since the first application in man
      (3) it has become wide spread for clinical investigation of human metabolism as
      well as for clinical pharmacology research. In this article some methodological
      aspects will be discussed and a few examples of the application of the technique
      will be given.

PMID- 9288568
TI  - Changes in free radical scavengers and lipid peroxide in thyroid glands of
      various thyroid disorders.
AB  - To clarify whether the changes of free radicals and its scavengers are induced by
      thyroid disorders, we measured levels of free radical scavengers and checked O2
      radical generating systems in the human thyroid gland. Thyroid specimens from
      patients with Graves' disease, follicular adenoma, and papillary and follicular
      carcinomas contained significantly higher concentrations of xanthine oxidase
      (XOD) and gluthathione peroxidase (GSH-PX), compared to those in the normal
      thyroid tissue. Catalase concentration was significantly lower in thyroid
      specimens from patients with Graves' disease and significantly lower in thyroid
      specimens from patients with follicular adenoma, compared to those in the normal
      thyroid tissue. Cu/Zn superoxide dismutase (Cu/Zn SOD) concentration was
      significantly lower in the specimens from follicular adenoma and papillary
      carcinoma and Mn SOD concentration was significantly higher in the specimens from
      papillary carcinoma than those in the normal thyroid tissue. The lipid peroxide
      concentration, expressed as malondialdehyde (MDA) concentration, was
      significantly higher in the specimens from papillary carcinoma than those in the
      normal thyroid tissue. These findings suggest that the levels of free radicals
      are increased and are scavenged and catalyzed in the thyroid of Graves' disease,
      whereas free radicals and lipid peroxide are not completely scavenged in
      papillary carcinoma tissues, suggesting that these substances affect some role in
      cell function of thyroid tumors.

PMID- 9288567
TI  - Glyceraldehyde 3-phosphate-induced DNA or protein modifications severely inhibit
      the protein/DNA interaction.
AB  - In this study, the effect of the reducing sugar glyceraldehyde 3-phosphate on
      protein/DNA interaction has been investigated. Treatment with glyceraldehyde 3
      phosphate of oligonucleotides recognized by various transcription factors
      severely inhibits protein binding. The inhibitory effect is time and dose
      dependent. Treatment with glyceraldehyde 3-phosphate of the homeodomain protein
      TTF-1 HD has also an inhibitory effect on the interaction with DNA, again in a
      time and dose-dependent manner. These "in vitro" effects could have "in vivo"
      counterparts and therefore contribute to molecular alterations observed either
      when intracellular protein are exposed to high doses of reducing sugars (i.e. in
      diabetes) or after a long time exposure (i.e. in Gzero-arrested cells during
      aging).

PMID- 9288569
TI  - Plasma uric acid and total antioxidant status in patients with diabetes mellitus.

PMID- 9288570
TI  - Hormonal studies in Cushing's syndrome during petrosal sinus catheterization:
      Part I: Existence of multihormonal gradients.

PMID- 9288571
TI  - Hyperglycemic hyperosmolar syndrome associated with severe ketosis in Japanese
      woman.

PMID- 9288572
TI  - Melatonin in relation to cellular antioxidative defense mechanisms.
AB  - Melatonin's actions in organisms are more widespread than originally envisaged.
      Over three decades ago, the changing pattern of nocturnal melatonin production
      was found to be the signal for the annual cycle of reproduction in photoperiodic
      species. Since then, melatonin's actions also have been linked to circadian
      rhythms, immune function, sleep, retinal physiology and endocrine functions in
      general. In recent years, however, the sphere of influence of melatonin was
      further expanded when the indole was found to be an effective free radical
      scavenger and antioxidant. Free radicals are toxic molecules, many being derived
      from oxygen, which are persistently produced and incessantly attack and damage
      molecules within cells; most frequently this damage is measured as peroxidized
      lipid products, carbonyl proteins, and DNA breakage or fragmentation.
      Collectively, the process of free radical damage to molecules is referred to as
      oxidative stress. Melatonin reduces oxidative stress by several means. Thus, the
      indole is an effective scavenger of both the highly toxic hydroxyl radical,
      produced by the 3 electron reduction of oxygen, and the peroxyl radical, which is
      generated during the oxidation of unsaturated lipids and which is sufficiently
      toxic to propagate lipid peroxidation. Additionally, melatonin may stimulate some
      important antioxidative enzymes, i.e., superoxide dismutase, glutathione
      peroxidase and glutathione reductase. In in vivo tests, melatonin in
      pharmacological doses has been found effective in reducing macromolecular damage
      that is a consequence of a variety of toxic agents, xenobiotics and experimental
      paradigms which induce free radical generation. In these studies, melatonin was
      found to significantly inhibit oxidative damage that is a consequence of paraquat
      toxicity, potassium cyanide administration, lipopolysaccharide treatment, kainic
      acid injection, carcinogen administration, carbon tetrachloride poisoning, etc.,
      as well as reducing the oxidation of macromolecules that occurs during strenuous
      exercise or ischemia-reperfusion. In experimental models which are used to study
      neurodegenerative changes associated with Alzheimer's and Parkinson disease,
      melatonin was found to be effective in reducing neuronal damage. Its lack of
      toxicity and the ease with which melatonin crosses morphophysiological barriers
      and enters subcellular compartments are essential features of this antioxidant.
      Thus far, most frequently pharmacological levels of melatonin have been used to
      combat oxygen toxicity. The role of physiological levels of melatonin, which are
      known to decrease with age, is being investigated as to their importance in the
      total antioxidative defense capacity of the organism.

PMID- 9288573
TI  - Corticotropin-releasing hormone-binding protein and its possible role in
      neuroendocrinological research.
AB  - Corticotropin-releasing hormone-binding protein (CRH-BP), predominately produced
      by the liver, is a glycoprotein with a molecular weight of 37 kDa. The mature
      protein consists of 7 exons and 6 introns, with 5 tandem disulfide bridges which
      are essential for the binding of corticotropin-releasing hormone (CRH). This
      binding protein is distributed and expressed differently from corticotropin
      releasing hormone receptors (CRH-Rs), as is the ligand requirement. Most CRH in
      plasma is bound to its binding protein, is therefore inactive and unable to bind
      to its receptor. Other competitives can reverse the binding, liberating CRH.
      Together with the CRH neuropeptides and CRH receptors, CRH-binding protein plays
      a role in the hypothalamic-pituitary-adrenal axis, in immune/inflammatory
      reactions as an auto/paracrine proinflammatory regulator, in pregnancy, as well
      as in some pathological conditions.

PMID- 9288575
TI  - Insulin-like growth factor-1 reverses diabetes-induced wound healing impairment
      in rats.
AB  - Impaired wound healing is an enigmatic and debilitating complication of diabetes.
      A consensus as to the pathogenesis of this disorder has yet to emerge. Recent
      concepts suggest that IGF-1 is an important regulator of the healing process. The
      level of this growth factor is reduced in the wound environment of diabetics. We
      tested the premise that IGF-1 administration may prevent or ameliorate wound
      healing impairment in streptozotocin (STZ, 55 mg/kg, iv) diabetic rats. IGF-1 (15
      micrograms/day) or placebo was infused via mini-osmotic pumps into standardized
      stainless steel dorsal wound chambers. Wound-related parameters including
      protein, DNA, hydroxyproline and macrophages were decreased as a function of
      diabetes. A 14-day treatment with IGF-1 reversed the diabetes effect and
      increased total hydroxyproline, DNA, protein and macrophage numbers by 48%, 52%,
      31% and 40% above vehicle-control values, respectively. The data support the
      premise that diabetes, related suppression of IGF-1 and/or macrophage function
      within the wound environment is responsible, at least in part, for the wound
      healing impairment in this disease state.

PMID- 9288574
TI  - Pioglitazone and metformin reverse insulin resistance induced by tumor necrosis
      factor-alpha in liver cells.
AB  - Tumor necrosis factor-alpha (TNF-alpha) has recently been implicated as a cause
      of insulin resistance (IR) in obesity and non-insulin dependent diabetes mellitus
      (NIDDM). To examine mechanisms involved, we induced IR induced IR in H-411 E
      cells with graded doses of TNF-alpha and measured the ability of insulin (INS) to
      stimulate both calmodulin (CaM) mRNA and glucose utilization. With TNF-alpha
      concentration at 1 ng/ml and 10(4) muU/ml INS, metformin 10 microM and
      pioglitazone 1.5 microM, reversed the IR induced by TNF-alpha restoring biologic
      response to 100% of INS effect alone. Furthermore, comparable results were
      obtained with glucose utilization/oxidation experiments in the H-411 E cells
      using glucose U-14C, trapping 14CO2 release in a hyamine filter and extracting
      14C labelled lipids with Dole's reagent. In condusion, these data add scientific
      support for the use of both metformin and pioglitazone in treatment of IR in
      NIDDM patients and support a rationale for use of use of these drugs alone, and
      in conjuction with oral agents and/or INS treatment.

PMID- 9288577
TI  - Insulin sensitivity and insulin response in women with gestational diabetes
      mellitus.
AB  - Gestational diabetes mellitus (GDM) is associated with much increased risk of
      developing diabetes later on in life. Using the frequently sampled intravenous
      glucose tolerance test and the minimal model analyses we have therefore
      determined the early insulin response to glucose (EIR) and insulin sensitivity
      (Si), in women with GDM of different severity (n = 14) and in normal women (n =
      10). During the last trimester of pregnancy. GDMs compared to controls had
      significantly lower EIR (p < 0.001) and Si (p < 0.01). The reduction in EIR was
      less marked in GDM patients treated with diet alone (n = 6) as compared to GMD
      patients (n = 8) who subsequently during pregnancy needed treatment also with
      insulin. The insulin treated GDM group only had higher fasting glucose level than
      controls (5.2 vs 4.2 mmol/l, p < 0.001). Both GDM subgroups had slightly elevated
      basal levels of FFA and 3-hydroxybutyrate. Si and EIR were inversely correlated
      in control women and their fasting glucose correlated both to EIR (r = 0.63, p <
      0.05) and to Si (r = 0.59, p < 0.05). In the GDM subgroups Si and EIR were
      unrelated and there were no correlations between fasting glucose and Si or EIR.
      These results suggest that glucose intolerance in GDM patients in the last
      trimester of pregnancy is characterized by both an impaired insulin secretion and
      an increased resistance to insulin. The impairment of insulin secretion and
      action increases with the severity of hyperglycemia, and the relative insulin
      deficiency characterizing GDM patients is associated with a selected defect in
      insulin action mainly affecting gluco-regulation.

PMID- 9288576
TI  - Effect of successful parathyroidectomy on hematopoietic progenitor cells and
      parameters of red blood cells in patients with primary hyperparathyroidism.
AB  - Elevated levels of parathyroid hormone (PTH) in primary and secondary
      hyperparathyroidism inhibit hematopoiesis at the level of hematopoietic
      progenitor cells, mainly the burst forming units-erythroid (BFUe). Removal of
      parathyroid adenomas is associated with an increase in hematopoietic progenitor
      cells. In contrast, a certain amount of PTH and calcium is needed to correct
      anemia after bleeding demonstrating that PTH has also a stimulatory effect on the
      bone marrow. We examined the effect of parathyroidectomy (PTX) in 10 patients
      with histologically proven primary hyperparathyroidism on hematopoietic
      progenitor cells and several parameters of red blood cells before and at 5, 30
      and 90 days after PTX. After successful surgery serum levels of iPTH (p < 0.01)
      and calcium (p < 0.001) decreased significantly. Subsequently a steady increase
      in all hematopoietic progenitor cell classes was observed reaching significance
      for BFUe only (p < 0.05). Red blood cells and hemoglobin reached nearly
      pretreatment values within 90 days after PTX after they had decreased due to
      surgery associated blood loss. 8 patients undergoing hemithyroidectomy without
      PTX showed a similar decrease in red blood cells and hemoglobin followed by a
      rise after the operation. The changes of these parameters did not differ
      significantly from the patients with pHPT. In contrast to the patients with pHPT,
      no changes in hematopoietic progenitor cells during the 90 days were observed.
      The presented data provide further evidence that increased PTH concentrations
      might inhibit hematopoiesis in humans in vivo. The inhibition can be reversed
      following PTX by normalisation of PTH concentrations.

PMID- 9288578
TI  - Oxidation of remnant-like particles from serum of diabetic patients, patients
      with ischemic heart disease and normal subjects.
AB  - Remnant-like particles (RLP) are reportedly involved in the pathogenesis of
      atherosclerosis, as are lipid peroxides. To assess the role of the oxidation of
      RLP in this disease, we compared the oxidation of RLP with that of total very low
      density lipoproteins (VLDL) obtained from the serum of 10 patients with ischemic
      heart disease (IHD), 10 patients with diabetes mellitus (DM) and 10 normal
      subjects by measuring the levels of thiobarbituric acid reactive substances
      (TBARS). Our results indicated that RLP were oxidized in vivo to a greater extent
      than total VLDL in all three groups of subjects. The serum levels of RLP were
      significantly higher in the patients than in the normal subjects. The oxidation
      of RLP may therefore be involved in the progression of atherosclerosis in
      patients with IHD or DM.

PMID- 9288579
TI  - Comparison of a new anti-glutamic acid decarboxylase (GAD) enzyme-linked
      immunosorbent assay (ELISA) with radioimmunoassay methods: a multicenter study.
AB  - Several methods are available for the measurement of antibodies to glutamic acid
      decarboxylase (anti GAD). These antibodies are valuable tools for the
      immunodiagnosis of insulin-dependent (type 1) diabetes mellitus (IDDM) and for
      the assessment of risk for the future development of IDDM. We here describe a new
      enzyme-linked immunosorbent assay (ELISA) for the detection of anti-GAD which was
      tested in a multicenter study. The results of the new anti-GAD ELISA correlate
      well with those obtained by radioimmunoassays (RIA) and they have a higher
      sensitivity (69%) and specificity (98%) compared to other anti-GAD enzyme
      immunoassays as determined in the IDW Proficiency Test Program for the detection
      of GAD antibodies. The new ELISA is simple and easy to perform, with convenient
      handling of the reagents. Quantitative and reproducible test results are
      available within approximately four hours. The new anti-GAD ELISA can be used for
      large scale population screening to indicate a prediabetic state as well as to
      diagnose autoimmune diabetes in adults (LADA) and the risk for IDDM in pregnant
      women with gestational diabetes.

PMID- 9288580
TI  - The efficacy of voglibose on daily glycemic excursions assessed by the "J"-index
      in non-insulin dependent diabetes mellitus.

PMID- 9288581
TI  - Hormonal studies in Cushing's syndrome during petrosal sinus catheterization.
      Part II: Absence of relationship between intestinal vasoactive peptide and
      prolactin.

PMID- 9288582
TI  - Urinary excretion of amphetamine after termination of drug abuse.
AB  - Important issues in urinary drug testing are the variability between consecutive
      urine specimens, the duration of positive specimens after last intake, and the
      usefulness of creatinine concentration to correct for variability in urine
      concentration. These issues were addressed in the present study with amphetamine
      as the drug of abuse. Drug users who were starting their sentences in prison
      participated in the study. Urine specimens were collected 1 to 5 times per day.
      Screening was performed by EMIT d.a.u. (cutoff, 0.30 microgram/mL) and EMIT II
      (cutoff, 1.00 microgram/mL), and confirmation was performed with gas
      chromatography-mass spectrometry. Creatinine and pH were recorded. Amphetamine
      was demonstrated in seven subjects. The highest concentration was 135
      micrograms/mL. The last positive-screened specimen was observed by EMIT d.a.u.
      after almost 9 days of imprisonment and by EMIT II after 3 days. Large
      concentration differences could be found between consecutive specimens,
      accompanied by considerable differences in creatinine and pH. The individual
      curves were generally smoother after creatinine correction of concentrations. As
      expected, urinary pH was observed to influence the excretion.

PMID- 9288583
TI  - Electrospray analysis of biological samples for trace amounts of trichloroacetic
      acid, dichloroacetic acid, and monochloroacetic acid.
AB  - Trichloroethylene (TCE) has been identified as a widespread groundwater
      contaminant. Trichloroacetic acid (TCA) and dichloroacetic acid (DCA) are
      toxicologically relevant metabolites of TCE that produce tumors in B6C3F1 mice. A
      sensitive method for measuring these metabolites in plasma has been developed to
      obtain pharmacokinetic data from TCE exposure. This is particularly important
      because DCA is more potent at producing hepatoproliferative lesions than TCA. At
      present, it is unclear whether DCA is produced by humans. Existing gas
      chromatographic methods cannot detect DCA at low nanogram-per-milliliter levels.
      A Finnigan TSQ 700 mass spectrometer (MS) with electrospray ionization was used
      to measure TCA, DCA, and monochloroacetic acid (MCA) in plasma. The MS was
      operated in negative ion tandem MS mode. The limit of detection for TCA and DCA
      was 4 ng/ml, and the limit of detection for MCA was 25 ng/mL. Plasma samples from
      human subjects exposed to 100 ppm TCE for 4 h contained TCA at concentrations as
      high as 10 micrograms/mL. DCA concentrations were less than 5 ng/mL, and MCA was
      not detected (less than 25 ng/mL).

PMID- 9288584
TI  - A sensitive GC-MS procedure for the analysis of flunitrazepam and its metabolites
      in urine.
AB  - Analysis of urine specimens collected from individuals ingesting 2 and 4 mg
      flunitrazepam (FN) showed positive results by OnLine and OnTrak immunoassays for
      up to 60 h. Gas chromatographic-mass spectrometric (GC-MS) analysis of these
      specimens for FN, 3-OH-FN, 7-amino-FN, 7-amino-3-OH-FN, desmethyl-FN, and 3-OH
      desmethyl-FN after glucuronidase treatment showed only low levels of 7-amino-FN
      with almost none of the other metabolites. These levels were far below the
      expected results based on the immunoassay data. This study reports on a GC-MS
      procedure for FN and the previously listed metabolites. The method is based on
      acid hydrolysis of the urine specimens, which converts FN and all its metabolites
      described previously to one of four amino-benzophenone derivatives (1-4) with
      oxazepam-d5 as the internal standard. Under the experimental conditions, the
      internal standard is converted to 2-amino-5-chloro-benzophenone-d5. The limit of
      detection for 7-amino-FN and 7-amino-desmethyl-FN and their 3-OH derivatives was
      less than 1 ng/mL. Analysis of urine specimens collected for 72-h postingestion
      of 1, 2, or 4 mg FN showed appreciable levels of benzophenone 3 (product of 7
      amino-FN and 7-amino-3-OH-FN) and lower levels of benzophenone 4 (product of 7
      amino-desmethyl-FN and 7-amino-3-OH-desmethyl-FN) with no detectable levels of
      benzophenones 1 and 2. The method makes it possible to confirm the presence of FN
      metabolites in urine at least 72-h postingestion of small doses of the drug.

PMID- 9288585
TI  - Flunitrazepam excretion patterns using the Abuscreen OnTrak and OnLine
      immunoassays: comparison with GC-MS.
AB  - A study was conducted to compare the performance of the OnLine and OnTrak
      immunoassays for benzodiazepines with gas chromatographic-mass spectrometric (GC
      MS) analysis in detecting flunitrazepam (FNP) and its metabolites in human urine.
      Urine was collected over a 72-h period from six individuals (four male and two
      female) who had taken a single oral dose of either 1 or 4 mg of FNP. The OnTrak
      assay was run at a 100-ng/mL cutoff of nordiazepam (NDP), and the OnLine assay
      was run with a standard curve from zero to 200 ng/mL of NDP with and without beta
      glucuronidase treatment. Each sample was analyzed by GC-MS using FNP, 7-amino
      FNP, 3-hydroxy-FNP, desmethyl-FNP, 7-amino-3-hydroxy-FNP, and desmethyl-3-hydroxy
      FNP as standards with beta-glucuronidase treatment. The specimens from the 1-mg
      dose did not yield a positive result by immunoassay over the 72-h collection
      period. Specimens from the 4-mg dose did yield positive results in both
      immunoassays. The time of the first positive result ranged from 4 to 12 h, and
      the time to the last positive result ranged from 18 to 60 h. Treatment of the
      samples with beta-glucuronidase increased the OnLine values between 20 and 60%,
      but it did not appreciably increase the detection time. GC-MS analysis showed no
      detectable levels of FNP, 3-hydroxy-FNP, desmethyl-FNP, 7-amino-3-hydroxy-FNP,
      and desmethyl-3-hydroxy-FNP. However, all samples collected past time zero showed
      detectable levels of 7-amino-FNP (> 2 ng/mL) with peak concentrations at 12-36 h.
      The peak levels of 7-amino-FNP by GC-MS paralleled the peak levels of the
      immunoassay response. The amount of 7-amino-FNP metabolite quantitated by GC-MS,
      however, accounted for only 15-20% of the total immunoassay crossreactive FNP
      metabolites.

PMID- 9288586
TI  - Morphine, morphine-3-glucuronide, morphine-6-glucuronide, and 6
      monoacetylmorphine determined by means of atmospheric pressure chemical
      ionization-mass spectrometry-liquid chromatography in body fluids of heroin
      victims.
AB  - Morphine, morphine-3-glucuronide (M3G), morphine-6-glucuronide (M6G), and 6
      monoacetylmorphine (6-MAM) were isolated from body fluids using solid-phase
      extraction and determined by means of atmospheric pressure chemical ionization
      mass spectrometry-liquid chromatography (APCI-LC-MS) in selected ion monitoring
      mode. The following ions were monitored: m/z 286 for morphine; m/z 286 and 462
      for M3G and M6G; m/z 211, 268, and 328 for 6-MAM; and m/z 289 for morphine-d3
      (internal standard). The recoveries ranged from 82 to 89% The limits of detection
      were as follows: 0.1 ng/mL (morphine), 0.5 ng/mL (6-MAM), and 1 ng/mL (M3G and
      M6G). The analytes were determined in samples taken from 21 heroin-overdose
      victims. Twenty-one blood samples, 11 cerebrospinal fluid (CSF) samples, 12
      vitreous humor (VH) samples, and 6 urine samples were investigated. Blood
      concentrations (ng/mL) of morphine ranged from 8 to 1539, of M3G from 111 to 941,
      of M6G from 32 to 332, and of 6-MAM from 0 to 73. The levels of morphine were
      correlated with glucuronide values and with 6-MAM. The concentrations of
      morphine, M3G, and M6G in CSF were, as a rule, lower than in blood and lower in
      VH than in CSF. The concentrations of morphine and molar ratios of M6G-morphine
      in blood and CSF were correlated. Low ratios of M3G-morphine and M6G-morphine in
      blood of heroin-overdose victims indicated short survival time after drug intake.

PMID- 9288587
TI  - Hair analysis for drugs of abuse. XVII. Simultaneous detection of PCP, PCHP, and
      PCPdiol in human hair for confirmation of PCP use.
AB  - The paper reports the simultaneous detection hair of phencyclidine (PCP) and its
      two major metabolites, 1-(1-phenylcyclohexyl)-4-hydroxypiperidine (PCHP) and
      trans-1-(1-phenyl-4-hydroxycyclohexyl)-4'-hydroxypiperidine (t-PCPdiol) in human
      hair. The detection of these metabolites provides definitive evidence that a
      positive hair analysis result is due to active PCP use and not due to external
      contamination of the hair specimen. Hair (5 mg) from known PCP users was washed
      three times with 0.1% sodium dodecyl sulfate for 1 min before analysis. Three
      extraction methods were compared: methanol-5N HCl (20:1) (Method A), 10% HCl
      (Method B), and 2N sodium hydroxide digestion (Method C). PCP-d5 and PCHP-d5 were
      used as internal standards. Extracts were purified by Bond Elut Certify solid
      phase extraction procedures. Samples were derivatized with N,O-bis-trimethylsilyl
      acetamide and analyzed by gas chromatography-mass spectrometry. Compared with
      Method A, the extraction efficiencies of Methods B and C for PCP were 83-89%;
      however, the extraction efficiencies of Methods B and C for the two metabolites
      were only half or less than that of Method A. Method A was therefore selected for
      the analysis of clinical hair specimens from eight PCP users. The coefficients of
      variation of this method (n = 5) for PCP at 4 ng/mg and for PCHP and t-PCPdiol at
      0.2 ng/mg were 2.13, 6.09, and 9.38%, respectively. In the eight hair specimens,
      PCP values ranged between 0.33 and 14 ng/mg. PCHP between 0.02 and 0.12 ng/mg,
      and trans-PCPdiol between 0.09 and 0.45 ng/mg. It was found that t-PCPdiol was
      the major metabolite in the PCP users' hair specimens, although t-PCPdiol was a
      minor metabolite in the hair specimens of rats intoxicated with PCP.

PMID- 9288588
TI  - An isotope-dilution gas chromatography-mass spectrometry method for trace
      analysis of xylene metabolites in tissues.
AB  - A gas chromatography-mass spectrometry (GC-MS) method using isotope dilution was
      developed to measure trace levels of xylene metabolites in brain tissues. The
      primary metabolites of xylene are dimethylphenol (DMP), methylbenzyl alcohol
      (MBA), toluic acid (TA), and methylhippuric acid (MHA). The internal standard was
      a mixture of deuterated DMP-d3, TA-d7, and MHA-d7. DMP-d3 was commercially
      available and was used as the internal standard for both DMP and MBA. TA-d7 and
      MHA-d7 were biosynthesized by administering xylene-d10 to rats and collecting
      their urine. Based on the noise peaks in 10 blank samples, the on-column limits
      of quantitation (mean +10 SD of noise peaks) were approximately 305, 1220, 545,
      and 386 pg for DMP, MBA, TA, and MHA, respectively. Analyte detection and
      recovery tests from brain tissues of control rats were conducted by spiking the
      tissues with 32 nmol/g of each analyte, together with the deuterated metabolites.
      The tissues were homogenized, extracted with ethyl acetate, and derivatized by
      trimethylsilylation. One microliter of the sample was injected into the GC-MS.
      The recoveries of the analytes were 104 +/- 8%, 80 +/- 9%, 93 +/- 10%, and 92 +/-
      11% (mean +/- SD, n = 7) for DMP, MBA, TA, and MHA, respectively. The tissue
      preparation efficiency, which was indicated by absolute recoveries of internal
      standards, was approximately 33% for DMP, MBA, and TA and approximately 80% for
      MHA. No metabolites were detected in untreated control tissues. This simple and
      sensitive method to simultaneously detect major xylene metabolites in brain
      tissues could also be used for the analysis of blood and urine samples from
      workers to monitor p-xylene exposure.

PMID- 9288589
TI  - Confirmation of ethanol compressed gas standard concentrations by an NIST
      traceable, absolute chemical method and comparison with wet breath alcohol
      simulators.
AB  - This study compares compressed-gas Ethanol Breath Standards (EBS) with wet
      simulators as calibration standards for breath alcohol analyzers. After reviewing
      the technical basis and traceability for the two calibration sources, new
      analytical data verifying the ethanol content of EBS gas are presented. Based on
      collection of ethanol in an impinger and titration using a modified California
      Department of Health method, the data confirm the alcohol content of EBS
      compressed gas standards by an absolute, wet chemical method. These results
      establish the concentration accuracy and the NIST traceability of the EBS gas by
      two independent methods, gas chromatographic analysis traceable to NIST standards
      and the new wet chemical method. Effluent gas from a wet simulator standard is
      then analyzed by the wet method to show its equivalence with EBS gas.

PMID- 9288590
TI  - Excretion of cannabinoids in urine after ingestion of cannabis seed oil.
AB  - Gas chromatographic-mass spectrometric (GC-MS) quantitation of 25 cannabis sed
      oils determined delta 9-tetrahydrocannabinol (THC) concentrations from 3 to 1500
      micrograms/g oil. In a pilot study, the morning urine of six volunteers who had
      ingested 11 or 22 g of the oil, which contained the highest THC content (1500
      micrograms/g), was collected for six days. The urine samples were screened by
      immunoassay, and the content of 11-nor-9-carboxy-delta 9-THC (THCCOOH) was
      determined by GC-MS. Urine samples were found cannabis positive for up to six
      days with THCCOOH-equivalent concentrations up to 243 ng/mL. by the Abuscreen
      OnLine immunoassay and THCCOOH contents from 5 to 431 ng/mL by the GC-MS method.
      All subjects reported THC-specific psychotropic effects.

PMID- 9288591
TI  - The analysis of thebaine in urine for the detection of poppy seed consumption.
AB  - The consumption of poppy seeds in various foods may lead to a positive opiate
      result in urine subjected to testing for drugs of abuse. As a natural constituent
      of poppy seeds, thebaine was investigated as a possible marker for poppy seed
      consumption. Poppy seeds were examined for opiate content by gas chromatography
      ion trap mass spectrometry (GC-MS) after extraction with methanol. Urine samples
      spiked with thebaine and urine from subjects given 11 g of poppy seeds were
      tested for the presence of thebaine, codeine, and morphine. Street heroin, one
      morphine and one codeine tablet, and urine from individuals who had used heroin
      were also examined for thebaine. Urine specimens were screened by enzyme
      immunoassay (EMIT) and confirmed for thebaine by GC-MS using a solid-phase
      extraction method. The GC-MS assay showed a linear response over a range of 1-100
      ng/mL and a limit of detection of 0.5 ng/mL. Thebaine was detectable in the urine
      of poppy seed eaters in concentrations ranging from 2 to 81 ng/mL. Because
      thebaine was absent in powdered drugs and the urine of true opiate drug users,
      thebaine is proposed as a direct marker for poppy seed use.

PMID- 9288592
TI  - Solid-phase extraction of THC metabolite from urine using the Empore disk
      cartridge prior to analysis by GC-MS.
AB  - The Empore disk cartridges (C18) were evaluated for sample preparation in the gas
      chromatography-mass spectrometry confirmational assay for the 11-nor-9-carboxy
      delta 9-tetrahydro-cannabinol (THCCOOH) metabolite. The performance of the Empore
      disk cartridges, determined by the recovery, precision, limit of detection (LOD),
      and limit of quantitation (LOQ) of the assay was comparable with the performance
      of a widely used solid-phase extraction cartridge (Spec C18 cartridges) and the
      traditional liquid-liquid extraction technique. The Empore disk cartridges showed
      an average recovery of 89% at low concentrations of 6 ng/mL of the THC metabolite
      spiked into urine. The recovery was consistent across three different lots of
      Empore disk cartridges. The within-run precision of the assay at a concentration
      of 18 ng/mL had a coefficient of variation of 2%, and the LOD and LOQ were
      determined to be 1 ng/mL.

PMID- 9288593
TI  - Analysis of zolpidem in human plasma by high-performance liquid chromatography
      with fluorescence detection: application to single-dose pharmacokinetic studies.
AB  - Zolpidem, an imidazopyradine hypnotic agent, can be quantitated by high
      performance liquid chromatography (HPLC) with fluorescence detection. After the
      addition of a structurally related internal standard (propyl-zolpidem), plasma
      samples were double-extracted at neutral pH with toluene-isoamyl alcohol or
      benzene-isoamyl alcohol. The organic extracts were evaporated to dryness,
      reconstituted with mobile phase, and analyzed by HPLC using a C-18 reversed-phase
      column, a mobile phase of acetonitrile-50mM potassium dihydrogen phosphate
      (50:50), and fluorescence detection with excitation and emission wavelengths of
      254 and 390 nm, respectively. The lower limit of reliable quantitation was in the
      range of 1-2.5 ng/mL. The method is applicable to single-dose pharmacokinetic
      studies of zolpidem in humans.

PMID- 9288594
TI  - The use of ELISA tests and immunoaffinity chromatography combined with reversed
      phase high-performance liquid chromatography for dexamethasone detection in
      equine urine.
AB  - Dexamethasone is a corticosteroid drug widely used in racehorses because of its
      anti-inflammatory effect. It is, therefore, frequently detected in antidoping
      tests. A method for the antidoping control of dexamethasone in equine urine using
      screening by ELISA and confirmation by immunoaffinity chromatography combined
      with reversed-phase high-performance liquid chromatography-diode array detection
      (HPLC-DAD) is described. The ELISA test is frequently used in antidoping tests
      for its sensitivity, relative speed, and low cost. The test showed linearity in
      the range of 4-500 ng/mL of urine, and the intra-assay and interassay imprecision
      were 9.4 and 9.7%, respectively. The confirmation method showed a limit of
      detection of 4 ng/mL for dexamethasone. The intra-assay and interassay
      imprecisions were 10.3 and 14.4%, respectively. The HPLC-DAD showed a limit of
      detection of 5 ng and linearity in the range of 25-500 ng of dexamethasone. The
      absolute method recovery was 56.4%. The proposed method detected dexamethasone up
      to 52 h after administration and proved to be adequate for the antidoping
      control.

PMID- 9288595
TI  - HPLC determination of flumethrin, deltamethrin, cypermethrin, and cyhalothrin
      residues in the milk and blood of lactating dairy cows.
AB  - A procedure to determine residue concentrations of synthetic pyrethroid
      insecticides (flumethrin, deltamethrin, cypermethrin and cyhalothrin) in the milk
      and blood of lactating dairy cows was developed. Extraction was performed with
      acetoritrile, n-hexane partitioning, and silica gel column cleanup with n-hexane
      and diethyl ether. Analysis was carried out by high-performance liquid
      chromatography and ultraviolet detection. Recovery of the four pyrethroids
      averaged 78 to 91% with a minimum detectable concentration of 0.001 mg/kg. The
      method was reproducible and sensitive.

PMID- 9288596
TI  - Urine adulteration with denture-cleaning tablets.

PMID- 9288597
TI  - Persistence of hepatitis B virus DNA in serum and liver from patients with
      chronic hepatitis B after loss of HBsAg.
AB  - BACKGROUND/AIMS: The persistence of serum and liver hepatitis B virus (HBV)
      sequences in patients with chronic hepatitis B after loss of HBsAg has already
      been described. We have attempted to elucidate the significance of these HBV
      sequences after loss of HBsAg. METHODS: Fifteen patients were studied. We looked
      for serum and liver HBV DNA, using polymerase chain reaction (PCR) with different
      sets of primers and in situ hybridization. The sedimentation velocity of serum
      HBV DNA was measured on a gradient of sucrose in two patients. RESULTS: Serum HBV
      DNA was detected by PCR in four of the 14 patients tested at 0 months after loss
      of HBsAg, two patients remained HBV DNA positive until 12 months, and none was
      positive at 24 months. The sedimentation velocity of serum HBV DNA in sucrose was
      relatively similar to that of a chronic HBV carrier with active viral
      replication. Liver HBV DNA was demonstrated by PCR in all 15 patients and by in
      situ hybridization in six patients. CONCLUSIONS: Our results show that: 1) HBV
      DNA may persist in the serum in a minority of patients and may be associated with
      circulating viral particles; 2) HBV DNA persists in the liver in all patients and
      its extrachromosomal localization was shown by in situ hybridization technique in
      some cases. These results suggest the persistence of low-level HBV replication
      after loss of HBsAg.

PMID- 9288598
TI  - MHC class II genes influence the susceptibility to chronic active hepatitis C.
AB  - BACKGROUND/AIMS: Chronic hepatitis C develops in more than 70% of hepatitis C
      virus infected subjects. Viral factors influence the disease course, but little
      is known about the importance of host factors. METHODS: Frequencies of major
      histocompatibility complex (MHC) class I and class II antigens were analyzed in
      two groups of patients with chronic hepatitis C virus infection and in control
      subjects. MHC class I typing was done by standard microlymphocytotoxicity assays.
      DRB1 and DQA1 genotyping was done by PCR based typing methods. RESULTS: DRB1*0301
      was found in 26 of 75 patients with chronic hepatitis C virus infection (34.7%)
      and in 12 of 101 control subjects (11.9%) (relative risk 3.9; p < 0.001).
      Homozygosity for this allele appeared to confer a stronger risk. In contrast,
      DRB1*1301 was detected in three subjects with persistent infection (4.0%)
      compared to 21 control subjects (20.8%) (relative risk 0.2; p < 0.008). This
      allele was linked with DQA1*0103, which was found in 10 patients (13.3%) compared
      to 34 control subjects (33.7%) (relative risk 0.31; p < 0.003). An even stronger
      protective effect was provided by the presence of DRB1*1301 and DQA1*0103
      (relative risk 0.08; p < 0.005). These findings were confirmed in a second group
      of chronic hepatitis C virus infected patients. CONCLUSIONS: The MHC class II
      allele DRB1*0301 appears to predispose to progression to chronic active hepatitis
      C, whereas the class II alleles DRB1*1301 and DQA1*0103 appear to provide
      protection against chronic active infection with hepatitis C virus.

PMID- 9288599
TI  - Evidence for a deficiency of interferon response in mononuclear cells from
      hepatitis C viremic patients.
AB  - BACKGROUND/AIMS: The pathophysiology of chronic hepatitis C and the mechanisms of
      resistance to interferon alpha are poorly understood. The aim of this work was to
      assess the influence of HCV infection and the viral genotype on lymphocyte
      production of 2',5' oligo-adenylate synthetase activity and monocyte production
      of TNF alpha and IL1 beta. METHODS: Mononuclear cells from 50 consecutive
      patients were studied after 6 months of interferon treatment. Patients with
      persistent viremia (PCR-positive, elevated ALT, n = 39) were compared with the
      PCR-negative patients with normal ALT activity (n = 11) of similar age and sex
      ratio. RESULTS: Cells from the viremic patients showed lower basal and stimulated
      2',5' oligo-adenylate synthetase activity, and a lower in vitro response capacity
      to human recombinant interferon. In contrast, no difference was observed in basal
      and stimulated TNF alpha or IL1 beta production between the two groups. In the
      PCR-positive patients the viral genotype had no significant influence on the
      response of mononuclear cells to interferon or endotoxin. CONCLUSIONS: These
      results show that the presence of HCV in blood is associated with an elective
      defect in interferon system activation, independently of the viral genotype.

PMID- 9288601
TI  - Prevalence and clinical and histological manifestation of hepatitis G/GBV-C
      infections in patients with elevated aminotransferases of unknown etiology.
AB  - BACKGROUND/AIMS: Hepatitis G virus (HGV) and hepatitis GB virus-C (GBV-C) are
      recently identified non-A-E hepatitis-associated viruses. The prevalence of
      HGV/GBV-C in the general population is high (1.0-1.7%), but data on the clinical
      and histological manifestations of the new viruses are sparse. In the present
      study we investigated the prevalence and clinical and histological manifestation
      of HGV/GBV-C infections in patients with elevated aminotransferase levels of
      unknown etiology. METHODS: In 52 of 630 consecutive patients referred for
      evaluation of elevated aminotransferases the underlying liver disease remained
      unknown. Serum samples of these 52 patients with elevated aminotransferase levels
      of unknown etiology were tested for HGV/GBV-C RNA by reverse transcription
      polymerase chain reaction (RT-PCR) using primers deduced from nonstructural
      regions. Cloned PCR products were sequenced and compared by phylogenetic
      analysis. RESULTS: HGV/GBV-C RNA was consistently detected in 7 of the 52
      patients (13%). Sequence and phylogenetic analysis revealed the presence of only
      one subtype, with nucleotide sequence homologies between 86 and 91%. All seven
      patients had persistent viremia for at least 9 months. In six patients liver
      function test results normalized, and alanine aminotransferase levels remained
      persistently elevated in only one patient. Four HGV/GBV-C positive and ten
      HGV/GBV-C negative patients consented to a liver biopsy, which revealed similar
      results with minimal to mild chronic hepatitis and mild portal fibrosis.
      CONCLUSIONS: The prevalence of HGV/GBV-C infections in patients with elevated
      aminotransferases of unknown etiology is low. Since clinical, biochemical and
      histomorphologic features of patients with elevated aminotransferases of unknown
      etiology with and without HGV/GBV-C infection are indistinguishable, the role of
      HGV/GBV-C in the pathogenesis of chronic liver disease appears insignificant.

PMID- 9288600
TI  - Interleukin-1 receptor antagonist plasma concentration is specifically increased
      by alpha-2A-interferon treatment.
AB  - BACKGROUND/AIMS: The mechanism of action of recombinant interferon-alpha (rIFN
      alpha) treatment in chronic hepatitis C is not fully understood, and may include
      modulation of the immune system as well as a direct antiviral effect. We have
      therefore evaluated the plasma concentrations of pro- and anti-inflammatory
      cytokines in patients with chronic hepatitis C before and during treatment with
      rIFN alpha. METHODS: Twenty-three patients were studied. Plasma concentrations of
      IL-1 beta, IL-6, TNF, IL-1 receptor antagonist (IL-1RA) and soluble TNF receptors
      (sTNFRs) type I and type II were determined twice before rIFN alpha treatment (on
      day -11 and day 1), and on days 11, 32 and 120 of treatment. RESULTS: IL-1 beta,
      IL-6 and TNF plasma concentrations were rarely increased before treatment (in
      one, six and seven patients, respectively), and usually declined during
      treatment. sTNFRs I and II plasma concentrations were not increased either before
      or during treatment. This was not the case for IL-1RA. In untreated patients, the
      plasma concentration of IL-1RA was higher than normal in 16 out of 23 patients.
      When rIFN alpha treatment was initiated, there was a constant and dramatic
      increase in IL-1RA levels, which reached 8 times the upper limit of the normal
      range (p < 0.001 as compared to pretreatment values). This increase was sustained
      up to day 120. CONCLUSIONS: These results indicate that induction of an anti
      inflammatory status through modulation of the IL-1/IL-1RA balance may be a key
      mechanism of action of rIFN alpha treatment in chronic hepatitis C.

PMID- 9288602
TI  - Continuous blood pressure monitoring in cirrhosis. Relations to splanchnic and
      systemic haemodynamics.
AB  - BACKGROUND/AIMS: Low arterial blood pressure is recognised as a distinctive
      factor in the hyperdynamic circulation in cirrhosis. 24-hour monitoring of the
      blood pressure and heart rate has recently revealed a reduced circadian variation
      with relation to liver function. However, associations with other clinical and
      haemodynamic characteristics have not been investigated and the aim of the
      present study was to identify splanchnic and systemic determinants of the 24-h
      blood pressure and heart rate in cirrhosis. METHODS: The variables were measured
      by an automatic ambulant device for monitoring blood pressure and related to the
      results of an invasive haemodynamic investigation, including measurements of
      intra-arterial blood pressure (9.00-11.00 h) in 37 patients with cirrhosis.
      RESULTS: The 24-h blood pressures were significantly lower and the heart rate was
      significantly higher in patients with cirrhosis than in matched controls (p <
      0.05-0.001). To identify determinants of 24-h or intra-arterial blood pressures
      and heart rate, pertinent variables were included in a multivariate regression
      model. This model revealed that independent determinants of a low 24-h arterial
      blood pressure were a high post-sinusoidal resistance, a low plasma volume, a
      short central circulation time, and the presence of ascites. In contrast, a low
      intra-arterial blood pressure was determined by a low serum sodium, a low
      haemoglobin, and a high cardiac output. Diuretic treatment did not influence this
      model. CONCLUSIONS: Although the 24-h blood pressure and the intra-arterial blood
      pressure were determined by different variables, the overall results indicate
      that abnormalities in both splanchnic and central haemodynamics and sodium-water
      retention are important in the pathophysiology of arterial hypotension in
      patients with portal hypertension.

PMID- 9288603
TI  - An economic analysis of norfloxacin prophylaxis against spontaneous bacterial
      peritonitis.
AB  - BACKGROUND/AIMS/METHODS: Spontaneous bacterial peritonitis (SBP) is a frequent
      complication of advanced liver disease and in high-risk patients, it is
      associated with a mean (per episode) mortality of 29% and a mean 1-year mortality
      of 82%. The 1-year recurrence rate of SBP can be as high as 30-70%. Selective
      intestinal decontamination with antibiotic prophylaxis has been shown to
      significantly reduce the incidence of recurrent SBP. The aim of this study was to
      perform an economic analysis of norfloxacin prophylaxis to prevent SBP
      recurrence. RESULTS: This analysis showed that norfloxacin prophylaxis in high
      risk patients with cirrhosis resulted in USD 4632 savings per patient per year by
      avoiding SBP and its associated expense. A sensitivity analysis showed that the
      norfloxacin prophylaxis remained cost-saving, even if it resulted in only a
      modest reduction in the SBP recurrence rate. CONCLUSIONS: Selective gut
      decontamination with norfloxacin is not only efficacious in preventing SBP, but
      can also be cost-saving by avoiding the resource utilization associated with its
      treatment.

PMID- 9288604
TI  - Plasma cholecystokinin and its precursors in hepatic cirrhosis.
AB  - BACKGROUND/AIMS: The liver influences the metabolism of several peptide hormones.
      The metabolic effect may, however, change considerably by diseases in the liver.
      This study examined whether hepatic cirrhosis influences the occurrence and
      concentrations of procholecystokinin (proCCK) and its products in plasma.
      METHODS: The sum of proCCK and its products (both processing intermediates and
      bioactive fragments) in plasma were measured by a recently developed "processing
      independent analysis". Bioactive forms of CCK in plasma were measured using a
      highly specific radioimmunoassay directed against the C-terminal epitope of CCK.
      RESULTS: In plasma from patients with primary biliary cirrhosis the basal
      concentration of the total proCCK product was increased. Moreover, a mixed meal
      increased plasma concentrations of both bioactive CCK (i.e. carboxyamidated an 0
      sulfated CCK peptides) and the total proCCK product in primary biliary cirrhosis.
      In contrast, plasma concentrations of bioactive CCK and the total proCCK product
      were normal in patients with alcoholic liver cirrhosis-both pre- or
      postprandially. The fraction of bioactive CCK in plasma from patients with both
      biliary and alcoholic cirrhosis was also normal. Hence, in primary biliary
      cirrhosis, alcoholic cirrhosis and in controls, respectively, bioactive CCK
      constituted 15%, 15% and 17% of the total proCCK product in the basal state; 70%,
      58% and 53% 30 min after and 48%, 56% and 51% 90 min after the meal. As shown by
      gel chromatography, plasma from patients with primary biliary cirrhosis and
      controls sampled 30 min after a meal contained CCK-33, -22 and -8-like peptides.
      In addition, plasma contained non-amidated (approximately non-bioactive) proCCK
      products corresponding in size to CCK-83, -58 and -33. Ninety minutes after a
      meal, CCK-8 predominated in plasma from patients with primary biliary cirrhosis,
      whereas plasma from controls displayed a CCK profile similar to that obtained 30
      min post-prandially. CONCLUSIONS: The results show that CCK-8 is metabolized at a
      slower rate in patients with primary biliary cirrhosis.

PMID- 9288605
TI  - Gallbladder motility and cholecystokinin secretion in chronic pancreatitis:
      relationship with exocrine pancreatic function.
AB  - BACKGROUND/AIMS: Postprandial gallbladder motility is regulated mainly by the
      hormone cholecystokinin (CCK). Since CCK secretion may be reduced in patients
      with pancreatic insufficiency (PI), we studied postprandial gallbladder motility
      in these patients. METHODS: Fifteen patients with PI due to chronic pancreatitis
      and 17 healthy control subjects were studied. Gallbladder volumes
      (ultrasonography) and plasma CCK concentrations (RIA) were determined at regular
      intervals for 120 min after meal ingestion. Urinary PABA and faecal fat excretion
      were measured to determine pancreatic exocrine function. RESULTS: Patients with
      PI had larger fasting gallbladder volumes than controls (48 +/- 6 cm3 versus 29
      +/- 2 cm3; p < 0.01). Gallbladder ejection volume at time 120 min was not
      significantly different between patients with PI (14 +/- 4 cm3) and controls (20
      +/- 2 cm3). However, the percentage postprandial gallbladder emptying in patients
      with PI was significantly reduced compared to controls (at 120 min: 29 +/- 8%
      versus 68 +/- 3%; p < 0.001). Residual postprandial gallbladder volume was
      increased in patients with PI compared to controls (at 120 min: 34 +/- 4 cm3
      versus 9 +/- 1 cm3; p < 0.001). Postprandial endogenous CCK secretion was
      significantly reduced in patients with PI compared to controls (78 +/- 13 pM.120
      min versus 155 +/- 14 pM.120 min; p < 0.001). Postprandial gallbladder emptying
      (%) was related to the degree of exocrine pancreatic insufficiency (r = 0.81; p <
      0.001). CONCLUSIONS: In patients with pancreatic insufficiency due to chronic
      pancreatitis: 1) fasting and residual postprandial gallbladder volumes are
      significantly increased; 2) postprandial CCK secretion and percentage gallbladder
      contraction are significantly reduced; 3) percentage postprandial gallbladder
      emptying is related to the degree of pancreatic exocrine insufficiency.

PMID- 9288606
TI  - Interphase cytogenetic analysis reveals numerical chromosome aberrations in large
      liver cell dysplasia.
AB  - BACKGROUND/AIMS: Little is known about genetic alterations in large or small
      liver cell dysplasia. The aim of this study was to determine whether these
      lesions present numerical chromosome aberrations. METHODS: Eight patients with
      hepatocellular carcinoma on cirrhosis, five with large liver cell dysplasia and
      three with small liver cell dysplasia, were analysed by in situ hybridization
      with different centromeric nucleic acid probes specific respectively for
      chromosomes 1, 7, 17 and 18. In each case results were compared between
      dysplastic, tumoral and non-dysplastic cirrhotic cells. Four normal livers were
      also studied with the same method and served as cytogenetic controls. RESULTS:
      All cases of large liver cell dysplasia dysplayed a polysomic population for each
      investigated chromosome. A high variability of numerical chromosome aberrations
      was observed with a copy number of chromosomes which ranged from two to more than
      six. By contrast, only one case of small liver cell dysplasia showed chromosomal
      anomalies. Numerical aberrations of at least one chromosome were observed in six
      of the eight hepatocellular carcinoma while the non-dysplastic cirrhosis and
      normal liver always showed a diploid pattern. CONCLUSIONS: These results
      demonstrate that cellular modifications in large liver cell dysplasia coexist
      with an early acquisition of genomic alterations, supporting the view that these
      phenotypic changes are preneoplastic.

PMID- 9288607
TI  - Effect of aflatoxin metabolism and DNA adduct formation on hepatocellular
      carcinoma among chronic hepatitis B carriers in Taiwan.
AB  - BACKGROUND/AIMS: Aflatoxins (AFs) are established hepatic carcinogens in several
      animal species. This study was performed to establish whether aflatoxin exposure
      may affect the risk of developing hepatocellular carcinoma in chronic hepatitis B
      virus carriers. METHODS: Urinary AF metabolites were measured for 43 HCC cases
      and 86 matched controls nested in a cohort of 7342 men in Taiwan. Thirty
      hepatocellular carcinoma cases and 63 controls were also tested for AFB1-albumin
      adducts. RESULTS: There was a dose-response relationship between urinary AFM1
      levels and risk of hepatocellular carcinoma in chronic hepatitis B virus
      carriers. Comparing the highest with the lowest tertile of urinary AFM1 levels,
      the multivariate-adjusted odds ratio (OR) was 6.0 (95% confidence interval (CI) =
      1.2-29.0). The hepatocellular carcinoma risk associated with AFB1 exposure was
      more striking among the hepatitis B virus carriers with detectable AFB1-N7
      guanine adducts in urine. Compared with chronic hepatitis B virus carriers who
      were negative for AFB1-albumin adducts and urinary AFB1-N7-guanine, no elevated
      risk was observed for those who were positive for either marker. But an extremely
      high risk of hepatocellular carcinoma among those having both markers was found
      (OR = 10.0, 95% CI = 1.6-60.9). The proportion of AFB1 converted to AFM1
      decreased with the progress of liver disease, whereas the formation of AFP1
      increased. The difference in patterns of AFB1 metabolite formation was an
      independent risk factor for hepatocellular carcinoma after adjustment for total
      AFB1 excretion. There was a synergistic interaction between glutathione S
      transferase M1 genotype and AFB1 exposure in hepatocellular carcinoma risk.
      CONCLUSIONS: AFB1 intake and expression of enzymes involved in AFB1
      activation/detoxification may play an important role in hepatitis B virus-related
      hepatocarcinogenesis.

PMID- 9288608
TI  - Hepatitis C virus infection in the development of hepatocellular carcinoma in
      cirrhosis.
AB  - BACKGROUND/AIMS: The role of hepatitis C virus replication and different
      genotypes in the progression of cirrhosis to hepatocellular carcinoma is examined
      on the basis of a prospective follow-up of 1438 patients with histologically
      proven cirrhosis. METHODS: The presence of HCV RNA, anti-HCV and characterisation
      of virus genotypes were determined in 72 cases who developed hepatocellular
      carcinoma after a median follow-up of 5.3 years (range 1 to 16) and compared to
      72 controls who had cirrhosis only, after a median follow-up of 4.8 years (range
      1 to 16). Patients in the hepatocellular carcinoma group and controls were
      matched, one to one, for age, sex, nationality, HBsAg seropositivity, duration of
      follow-up and aetiology of cirrhosis. RESULTS: HCV RNA was detected in 31 of 72
      (44%) patients who developed hepatocellular carcinoma, significantly more
      frequently than in 17 of 72 (23%) controls with cirrhosis (odds ratio 2.4, 95%
      confidence interval 1.2 to 5.0; p = 0.013). When cirrhosis of different
      aetiologies was analysed, hepatitis C virus replication was more frequently
      detected in patients developing hepatocellular carcinoma in association with
      cryptogenic cirrhosis (p = 0.007), alcoholic cirrhosis (p = 0.043) and hepatitis
      B virus seronegative cirrhosis (p = 0.05). Hepatitis C virus genotypes 1b and 4
      were the most prevalent; they were found in 53% and 25%, respectively, of the
      patients studied, but were equally distributed between cirrhosis progressing to
      hepatocellular carcinoma and controls. CONCLUSIONS: Persistent hepatitis C virus
      replication is closely associated with hepatocellular carcinoma development in
      cirrhosis, and there is no preferential role of individual hepatitis C virus
      genotypes.

PMID- 9288609
TI  - Aberrant dipeptidyl peptidase IV (DPP IV/CD26) expression in human hepatocellular
      carcinoma.
AB  - BACKGROUND/AIMS: Diagnosis of small nodular lesions in the liver is often
      difficult because polarization of hepatocytes under pathological conditions is
      not as easily determined as for glandular or squamous epithelia. The aim of the
      present study was to investigate whether the bile canalicular enzyme dipeptidyl
      peptidase IV (DPP IV) would be useful to assess the pattern of hepatocellular
      surface polarity in liver sections. METHODS: Expression of DPP IV activity was
      determined by enzymatic cytochemistry and image cytometry in 25 human
      hepatocellular carcinomas and five cirrhotic livers removed at transplantation.
      Samples from the central and/or peripheral portion of neoplastic nodules and from
      surrounding tissue were analyzed in each case. Control specimens were obtained
      from normal liver of seven patients who underwent surgery for non-neoplastic
      conditions. RESULTS: In normal liver, DPP IV activity was confined to the bile
      canalicular plasma membrane with a zone 3 predominance in the hepatic acinus.
      This was also the case in the majority of pathological non-neoplastic livers, but
      the cell distribution pattern of DPP IV was altered in all hepatocellular
      carcinomas: 2/25 cases were completely devoid of DPP IV activity and in the
      remaining 23 DPP IV expressing hepatocellular carcinomas, three different
      patterns were observed that deviated distinctly from the typical canalicular
      pattern: (i) canaliculi were distorted and convoluted and contained an abnormally
      high DPP IV activity; (ii) canalicular activity was lost and enzymatic activity
      was restricted to isolated spots; (iii) pseudoacinar structures of hepatocytes
      with both basolateral and apical DPP IV expression appeared. CONCLUSIONS: It is
      concluded that DPP IV is a useful bile canalicular enzyme to assess the
      functional polarization of hepatocytes and that aberrant DPP IV expression occurs
      in human hepatocellular carcinoma.

PMID- 9288610
TI  - Profiles of bile acids and progesterone metabolites in the urine and serum of
      women with intrahepatic cholestasis of pregnancy.
AB  - BACKGROUND/AIMS AND METHODS: The etiology of intrahepatic cholestasis of
      pregnancy (JCP) is unknown. We have performed comprehensive chromatographic and
      mass spectrometric analyses of progesterone metabolites and bile acids in serum
      and urine of six patients in order to characterize changes that might be of
      importance for the development of the disease. RESULTS: Conjugated bile acids
      were increased in serum and urine of patients with ICP while the levels of
      unconjugated bile acids were similar in healthy pregnancies and ICP. Unconjugated
      and conjugated 7 alpha, 12 alpha-dihydroxy-3-oxo-4-cholenoic acid was excreted in
      urine both in healthy pregnancies and in ICP, possibly indicating a rate
      limitation of 3-oxo-delta 4-steroid 5 beta-reductase in pregnancy. The serum
      levels and urinary excretion of total sulfated progesterone metabolites were
      increased in ICP while the glucuronides were unchanged or low. Confirming
      previous results, the fraction of metabolites with 3 alpha-hydroxy-5 alpha(H)
      configuration was increased. The urinary excretion of 5 alpha-pregnane-3 alpha,
      20 alpha-diol 3-sulfate, 20-N-acetylglucosaminide was greatly increased in ICP,
      as was that of 3 alpha-hydroxy-5 alpha-androstane-17 beta-carboxylic acid,
      assumed to be a progesterone metabolite. CONCLUSIONS: The combined results of
      this and previous studies are compatible with a primary change in the reductive
      metabolism of progesterone in ICP, resulting in increased formation of
      metabolites with a 3 alpha-hydroxy-5 alpha(H) configuration and a larger fraction
      of sulfates. There also seems to be a selective defect in the biliary secretion
      of sulfated metabolites, particularly disulfates.

PMID- 9288611
TI  - Screening for Wilson's disease in patients with liver diseases by serum
      ceruloplasmin.
AB  - BACKGROUND/AIMS: A low serum ceruloplasmin level is considered a diagnostic test
      for Wilson's disease. To examine whether it is useful to detect presymptomatic
      patients with Wilson's disease, serum ceruloplasmin was determined by radial
      immunodiffusion (normal: 20-60 mg/dl) in all patients (n = 2867) admitted for
      evaluation of a liver disease in 1993 and 1994. METHODS: Patients with levels
      lower than 20 mg/dl were further evaluated by determination of serum copper
      concentration, urine copper excretion and ophthalmological examination. If
      possible, a liver biopsy was performed and the hepatic copper content was
      determined by flame atomic absorption spectroscopy. RESULTS: Seventeen patients
      had serum ceruloplasmin levels < 20 mg/dl. One had asymptomatic Wilson's disease
      (no Kayser-Fleischer rings or neurological symptoms). In the other 16 patients
      Wilson's disease was excluded. Based on elevated hepatic copper concentration,
      there were considered as heterozygous carriers of the WD gene. The remaining
      patients had various liver diseases (acute viral hepatitis in three, chronic
      hepatitis in two, drug-induced liver disease in three, alcoholic induced liver
      disease in two) or malabsorption (n = 3). CONCLUSIONS: The positive predictive
      value of low serum ceruloplasmin was only 5.9%. Although helpful for identifying
      presymptomatic Wilson's disease, screening by determination of serum
      ceruloplasmin in unselected patients with clinical or laboratory evidence of
      liver disease is neither feasible nor cost effective.

PMID- 9288612
TI  - Antioxidant enzyme status in biliary obstructed rats: effects of N
      acetylcysteine.
AB  - BACKGROUND/AIMS: N-acetylcysteine (NAC) is a modulator of thiol levels that
      protects against hepatotoxic agents. The aim of this study was to investigate
      whether NAC might improve hepatic antioxidant defenses in chronically biliary
      obstructed rats. METHODS: Secondary biliary cirrhosis was induced by 28 days of
      bile-duct obstruction. Groups of control and cirrhotic animals received NAC (50
      mumol .kg-1.d-1 i.m.) through the experimental period. RESULTS: Bile-duct
      obstruction resulted in decreased liver glutathione concentrations.
      Dichlorofluorescein (DCF) and thiobarbituric acid reactive substances (TBARS)
      concentrations, measured as markers of production of reactive oxygen species and
      lipid peroxidation, respectively, were significantly increased. Microsomal and
      mitochondrial membrane fluidity and the activities of catalase, cytosolic and
      mitochondrial superoxide dismutase (SOD), glutathione S-transferase, and
      cytosolic and mitochondrial Se-dependent and Se-independent glutathione
      peroxidase (GPx) were significantly reduced. NAC corrected the reduction in
      glutathione concentration and partially prevented the increases in DCF and TBARS
      concentrations. In addition, NAC treatment resulted in significant preservation
      of membrane fluidity and of the activities of catalase, mitochondrial SOD and the
      different forms of GPx. CONCLUSIONS: Our data indicate that NAC maintains
      antioxidant defenses in biliary obstructed rats. These effects of NAC suggest
      that it may be a useful agent to preserve liver function in patients with biliary
      obstruction.

PMID- 9288613
TI  - gamma-Interferon inhibits secretin-induced choleresis and cholangiocyte
      proliferation in a murine model of cirrhosis.
AB  - BACKGROUND/AIMS: Cholangiocyte proliferation is associated with increased
      secretin receptor gene expression and secretin-induced choleresis. Since gamma
      interferon has antiproliferative effects, we tested the hypothesis that gamma
      interferon inhibits ductal proliferation and secretin-stimulated choleresis
      associated with cirrhosis. METHODS: Mice were treated with 0.1 ml of 25% carbon
      tetrachloride intraperitoneally twice weekly and 5% alcohol in drinking water for
      12 weeks to induce cirrhosis and subsequently gamma-interferon 10(5)
      intramuscularly was administered daily for 10 weeks. We measured the effects of
      carbon tetrachloride and gamma-interferon on liver collagen content by
      morphometric analysis and hydroxyproline content. We measured the effects of
      gamma-interferon on ductal mass by morphometry and on ductal secretion by
      assessment of secretin receptor gene expression and secretin-induced choleresis.
      RESULTS: Compared to controls, there was an increase in liver hydroxyproline
      content of carbon tetrachloride-treated mice with histologic evidence of
      cirrhosis. Gamma-interferon treatment significantly decreased collagen liver
      content with loss of histologic features of cirrhosis. Morphometry revealed an
      increased number of bile ducts in cirrhotic mice as compared to controls or
      cirrhotics who received gamma-interferon. Secretin receptor mRNA levels were
      higher in cirrhotic mice compared to controls but this increase was inhibited by
      gamma-interferon. Secretin stimulated ductal secretion in cirrhotic mice but not
      control or cirrhotic mice who received gamma-interferon. CONCLUSIONS: We have
      established a murine model for cirrhosis and have shown, consistent with our
      hypothesis, that gamma-interferon decreases collagen content, ductal mass and
      secretin-induced choleresis incirrhotic mice.

PMID- 9288614
TI  - Stimulation of liver regeneration and function after partial hepatectomy in
      cirrhotic rats by continuous infusion of recombinant human hepatocyte growth
      factor.
AB  - BACKGROUND/AIMS: Radical resection is accepted as one of the most curative
      treatments for hepatocellular carcinoma. However, most patients have coexisting
      cirrhosis and their liver function is usually impaired. It is therefore important
      to stimulate the regeneration and function of the remnant cirrhotic liver after
      hepatectomy. Hepatocyte growth factor is a potent mitogen that has been suggested
      to play a crucial role in liver regeneration. METHODS: In this study, we
      performed 45% hepatectomy in rats with cirrhosis induced by thioacetamide, and
      administered recombinant human hepatocyte growth factor (rhHGF) with dextran
      sulfate by continuous infusion into the jugular vein with an infusion pump.
      RESULTS: rhHGF stimulated an increase in the wet weight of the remnant liver
      compared with untreated control rats. The proliferating cell nuclear antigen
      labeling index showed that this increase resulted from the stimulation of DNA
      synthesis. Serum levels of liver enzymes increased after hepatectomy, but
      returned to the prehepatectomy level more rapidly in rhHGF-treated rats than in
      controls. rhHGF increased hepatic protein synthesis above prehepatectomy levels
      and also markedly increased the serum levels of hepatic lipid metabolites.
      CONCLUSIONS: These results demonstrate that continuous intravenous infusion of
      rhHGF enhances the growth and function of the remnant liver in rats with
      cirrhosis after partial hepatectomy. Therefore, rhHGF may be useful after hepatic
      resection in patients with cirrhosis.

PMID- 9288615
TI  - Halofuginone, a specific inhibitor of collagen type I synthesis, prevents
      dimethylnitrosamine-induced liver cirrhosis.
AB  - BACKGROUND/AIMS: Hepatic cirrhosis is characterized by excessive deposition of
      collagen, resulting from an increase in type I collagen gene transcription. We
      evaluated the effect of halofuginone-a specific inhibitor of collagen type alpha
      1(I) gene expression-on dimethylnitrosamine (DMN)-induced liver
      fibrosis/cirrhosis in rats. METHODS: Fibrosis was induced by intraperitoneal
      injection of DMN. Halofuginone (5 mg/kg) was added to the diet. Collagen was
      stained with Sirius red and collagen alpha 1(I) gene expression was evaluated by
      in situ hybridization. RESULTS: In control rats, a low level of collagen alpha
      1(I) gene expression was observed. A high dose of DMN (1%) caused severe
      fibrosis, as indicated by induction of collagen alpha 1(I) gene expression and
      increased liver collagen content. Addition of halofuginone before the onset of
      fibrosis, almost completely prevented the increase in collagen type I gene
      expression and resulted in lower liver collagen content. Moreover, halofuginone
      partially prevented the marked decrease in liver weight and reduced the mortality
      rate. At a lower dose of DMN (0.25%), which causes mild fibrosis, halofuginone
      prevented the increase in collagen alpha 1(I) gene expression, prevented the
      increase in liver collagen deposition and reduced plasma alkaline phosphatase
      activity, all of which are characteristic of liver fibrosis/ cirrhosis.
      CONCLUSIONS: These results suggest that halofuginone can be used as an important
      tool to understand the regulation of the collagen alpha 1(I) gene and may become
      a novel and promising antifibrotic agent for liver fibrosis/ cirrhosis.

PMID- 9288617
TI  - Choledocholithiasis in a patient with Crohn's disease and choledochal varices.

PMID- 9288616
TI  - Acute hepatitis caused by alverine associated with anti-lamin A and C
      autoantibodies.
AB  - We report the case of a 67-year-old woman in whom onset and regression of acute
      hepatitis were closely related to the time of administration and withdrawal of
      the smooth muscle relaxant alverine. Antinuclear antibodies were positive, and
      their titer followed the course of hepatitis. They presented a smooth rim-like
      nuclear immunofluorescence staining pattern. Immunoblot assay showed that they
      were directed against lamin A and lamin C. This suggests that alverine should be
      added to the list of drugs known to produce acute hepatitis, and that drug
      induced liver injury is a possible cause of antinuclear antibodies specific for
      lamin A and lamin C.

PMID- 9288618
TI  - Apoptosis in liver disease.

PMID- 9288619
TI  - The pathogenesis of growth failure in paediatric liver disease.

PMID- 9288620
TI  - Increased serum soluble Fas (sFas) concentrations in HCV-positive patients with
      liver cirrhosis.

PMID- 9288621
TI  - Timing of IFN therapy initiation for acute hepatitis C after accidental
      needlestick.

PMID- 9288622
TI  - Co-transmission of hepatitis C and G viruses.

PMID- 9288623
TI  - Transmission of hepatitis G virus in HCV-infected couples: myth or reality?

PMID- 9288624
TI  - Dopa-responsive dystonia: a syndrome of selective nigrostriatal dopaminergic
      deficiency.
AB  - Dopa-responsive dystonia (DRD) is no longer a rare oddity. For the clinician, DRD
      poses a diagnostic challenge as its clinical presentation can be quite diverse.
      Marked and sustained response to L-dopa is the most crucial and absolute hallmark
      in confirming a diagnosis. Absence of degenerative nigral cell loss underlies the
      remarkable L-dopa response. The broadening spectrum of the clinical
      presentations, progress in molecular genetics with evidence of incomplete
      penetrance and phenotypic variability, biochemistry, utility of nuclear imaging
      in differential diagnosis, and treatment are discussed. I propose the concept of
      DRD as a syndrome, defined as selective nigrostriatal dopamine deficiency caused
      by genetic defects in dopamine synthesis without degenerative cell loss. I
      further propose the term DRD-plus, defined as inherited metabolic disorders which
      have symptomatic features of DRD, and those features not seen in DRD as well.

PMID- 9288625
TI  - Reconstitution of class I MHC molecules expressed in E. coli and complexed with
      single antigenic peptides.
AB  - The HLA-Cw3 heavy chain has been expressed at high level as insoluble protein
      aggregates in E. coli. The protein aggregates dissolved in strong denaturant
      solution were efficiently reconstituted by removal of denaturant in the presence
      of an HLA-Cw3 binding peptide (FAM) and beta 2m. The reconstituted HLA-Cw3/FAM
      protein binds specifically to a p58 natural killer cell inhibitory receptor, a
      natural ligand. The HLA-A2 molecule has also been reconstituted in complex with
      either of a peptide from myelin associated glycoprotein (MAG) or a peptide from
      the GAG protein of human immunodeficiency virus. The HLA-A2/MAG protein
      crystallized under the identical conditions as HLA-A2 purified from human
      lymphoblastoid cells. The reconstitution method has yielded an abundant supply of
      HLA molecules complexed with single antigenic peptides, and may be of general
      utility in reconstituting any class I MHC molecules. However, the HLA molecules
      could not be reconstituted either without a peptide or with an irrelevant
      peptide. Using this property, the reconstitution method could be used to
      determine whether a peptide is restricted/bound to certain class I MHC molecule.

PMID- 9288626
TI  - Reduced dihydroxyacetone sensitivity and normal sensitivity to glyceraldehyde and
      oxidizing agent of ATP-sensitive K+ channels of pancreatic beta cells in NIDDM
      rats.
AB  - The inhibition of ATP-sensitive K+(KATP) channels in pancreatic beta cells is a
      key step of insulin secretion induced by glucose. Glucose-induced insulin
      secretion from the beta cells is selectively impaired in patients with noninsulin
      dependent diabetes mellitus (NIDDM) and in animal models of it. In order to
      clarify the site of this abnormal glucose response, we studied the effects of
      insulin secretagogues and sulfhydryl oxidizing agent, 2,2'-dithio-bis (5
      nitropyridine) (DTBNP), on KATP channels in single beta cells of neonatally
      streptozotocin-induced NIDDM rats. We used the patch-clamp technique in cell
      attached mode (Vpipette = 0 mV). The inhibitory response to glucose of KATP
      channels was lacking in NIDDM rats, indicating reduced sensitivity to glucose of
      the channels. Glyceraldehyde (2-5 mM) in the diabetic beta cells elicited the
      same KATP channel inhibition as that obtained in controls. In contrast,
      dihydroxyacetone (DHA, 2-10 mM) sensitivity of KATP channels was significantly
      reduced in the beta cells of NIDDM rats. KATP channels in the diabetic beta cells
      were rapidly inhibited by 50 microM DTBNP, just as in the normal beta cells,
      suggesting that KATP channel function was normal. This indicates that one of the
      sites responsible for impaired glucose-induced insulin secretion in the
      pancreatic beta cells of NIDDM rats is located in the glycerol phosphate shuttle.

PMID- 9288627
TI  - Inhibition of diabetes in non-obese diabetic mice by nicotinamide treatment for 5
      weeks at the early age.
AB  - To know the effects of nicotinamide (NCT) treatment for 5 weeks at the early age
      on insulitis and development of diabetes in non-obese diabetic (NOD) mice, this
      experiment was performed. Ten ICR (Institute of Cancer Research) and 15 female
      NOD mice at 4 weeks of age were used. Mice were assigned to ICR and NOD groups,
      and NOD mice were randomly divided to control and NCT-treated groups. NCT was
      administered to mice orally as a solution and in a dose of 500 mg/kg body weight
      a day from the age of 4 to 8 weeks. Diabetes onset was 18 weeks of age in control
      group, and 22 weeks of age in NCT-treated group. Cumulative incidences of
      diabetes at 25 weeks of age in control and NCT-treated NOD mice were 63 and 29%,
      respectively. Insulitis occurred in all NOD mice. Incidence of insulitis in total
      islets was decreased by NCT treatment in diabetic NOD mice, but intensity of
      insulitis was not improved by NCT treatment. Blood glucose level was increased
      markedly, and plasma insulin level was decreased by diabetes development in NOD
      mice. Plasma triglycerides and total cholesterol levels were increased in
      diabetic mice than in non-diabetic mice. In conclusion, these results suggest
      that NCT treatment for 5 weeks at the early age in NOD mice inhibits development
      of diabetes and insulitis in diabetic NOD mice.

PMID- 9288628
TI  - Clinical trial of low dose cytosine arabinoside in the treatment of acute
      promyelocytic leukemia.
AB  - The purpose of this study is to determine the efficacy of low dose cytosine
      arabinoside (LD Ara-C) as an alternative treatment to conventional cytotoxic
      induction chemotherapy in childhood acute promyelocytic leukemia (APL). Four
      children with APL in poor medical condition prior to chemotherapy were treated
      with LD Ara-C (10 mg/m2/12 h) for 3 weeks. In three patients, the second course
      was administered after a resting period of two weeks. Subsequent conventional
      cytotoxic induction chemotherapy was applied in patients who did not enter
      complete remission (CR). After induction of CR, maintenance chemotherapy with a
      conventional monthly multi-drug regimen was applied. CR in one patient and
      partial remission (PR) in two patients were obtained after two courses of LD Ara
      C. Patients who did not enter CR after LD Ara-C entered on subsequent
      conventional chemotherapy. There were no major complications such as intracranial
      hemorrhage and sepsis; myelosuppression was not as severe as in conventional
      chemotherapy; there was clinical and laboratory improvement in coagulopathy. We
      concluded that LD Ara-C may be an alternative treatment to the conventional
      chemotherapy in children with APL, especially in whom conventional cytotoxic
      induction chemotherapy is thought to increase the risk of serious complications
      and early fatality during induction chemotherapy.

PMID- 9288629
TI  - Expression of HuD (a paraneoplastic encephalomyelitis antigen) mRNA in lung
      cancer.
AB  - HuD, one of the Hu antigens (HuD and HuC), was recognized in the sera of small
      cell lung cancer (SCLC) patients with antibody-associated paraneoplastic
      encephalomyelitis/peripheral sensory neuropathy (PEM/PSN). Three forms of HuD
      mRNA, 197, 156, 110 nucleotides are made by alternative splicing at 868-909
      residues and an additional 3'-splice site. To determine the diagnostic value of
      the HuD expression for small cell lung cancer, we examined 4 SCLC cell lines, 9
      surgically resected SCLCs, and 12 surgically resected non-SCLCs using the reverse
      transcriptase-polymerase chain reaction with the HuD-specific primer pairs that
      spanned the putative alternative 3'-splicing site and direct DNA sequencing. None
      of the patients were associated with PEM/PSN. A single RNA transcript (156
      nucleotides) among three forms (110, 156, 197 nucleotides) of the HuD gene was an
      alternatively spliced at 868-909 residues in SCLC cell lines. Expression of the
      HuD gene was stronger in three classic cell lines, but not in a variant cell
      line. Two of 9 SCLCs (22%) and 3 of 12 non-SCLCs (25%) expressed only the major
      RNA transcript (156 nucleotides) of the HuD gene, which was alternatively spliced
      in the same fashion as the cell line. These results revealed that no aberrant
      alternative splicing occurred in SCLC not associated with PEM/PSN and the
      expression of HuD gene was not specific for a particular histologic subtype of
      human lung cancer.

PMID- 9288630
TI  - Amplification of c-erbB-2 proto-oncogene in cancer foci, adjacent normal,
      metastatic and normal tissues of human primary gastric adenocarcinomas.
AB  - Genetic damages are frequently found in both tumor and normal cells at carcinogen
      exposed areas in the patients with upper aerodigestive tract cancer. These
      phenomena are explained by the multistage process and/or field cancerization
      theories. The c-erbB-2 proto-oncogene has been amplified in many human tumors
      including breast, stomach, kidney and lung cancers. To study the possible
      evidence of multistage process and/or field cancerization in the development of
      gastric adenocarcinoma, the amplification statuses of c-erbB-2 proto-oncogene
      using the Southern hybridization technique were evaluated at the 45 gastric
      adenocarcinoma specimen sets consisting of tumor tissue, adjacent normal tissue
      (within 2 cm of the primary tumor), metastatic tissue and normal stomach tissue
      (at least 5 cm away from primary tumor). As a result, c-erbB-2 proto-oncogene at
      2 specimen sets (4.4%) was amplified 2- to 4-fold to normal control status. In
      these 2 cases, c-erbB-2 proto-oncogene at histologically normal tissue adjacent
      to tumor tissue was amplified. And, the metastatic tissue of 1 case also
      exhibited c-erbB-2 proto-oncogene amplification of which the degree was less than
      that of tumor tissue. From these results, we were able to suspect that c-erbB-2
      proto-oncogene amplification in the normal tissue adjacent to tumor tissue could
      be a biomarker of premalignant changes in a small proportion of gastric
      adenocarcinoma patients. And, this result might suggest the possible role of
      multistage process and/or field cancerization in the development of gastric
      adenocarcinoma.

PMID- 9288631
TI  - Glutathione recycling is attenuated by acute ethanol feeding in rat liver.
AB  - The mechanism for ethanol-induced oxidative stress has been disputed because of
      the controversies on modulation of radical generating and scavenging activities
      by ethanol. In the present work, we attempted to clarify the acute effect of
      ethanol on the radical generating system as well as the radical scavenging
      system. For that purpose, chow-fed rats were given ethanol (5 g/kg) or isocaloric
      glucose solution by intragastric intubation and placed at 32 degrees C for 6 hr.
      Acute ethanol administration enhanced the expression of cytochrome P450 II E1(CYP
      II E1) in the liver and attenuated the activities of hepatic glutathione
      peroxidase (GPx) and reductase (GR). It also caused a significant increase in the
      level of hepatic thiobarbituric acid reactive substances (TBARS), an indicator of
      lipid peroxidation. On the other hand, acute ethanol feeding had no effect on the
      activities of catalase, xanthine oxidase (XO), glutathione transferase (GST) and
      glucose-6-phosphate dehydrogenase (G6PDH). From this result, it is suggested that
      acute ethanol administration causes the oxidative tissue damage by CYP II E1
      associated radical generation and the decreased radical scavenging function due
      to the reduced activities of hepatic glutathione recycling system such as GPx and
      GR.

PMID- 9288632
TI  - Analysis of clonality by X chromosome inactivation in uterine cervix cancer.
AB  - The determination of a unicellular or a multicellular origin of a tumor is an
      important due for understanding its etiology. To investigate this issue, we
      performed clonality assay of cervix cancer using polymerase chain reaction based
      on highly polymorphic locus of the androgen receptor gene, in which methylation
      of DNA correlates with inactivation of X chromosome. DNA samples were obtained
      from formalin-fixed, paraffin-embedded tissue of 20 invasive epidermoid
      carcinomas and 10 carcinoma in situ. Seven of ten carcinoma in situ, heterozygous
      for the androgen receptor locus, were monoclonal pattern. Among twenty invasive
      epidermoid carcinomas, eighteen of which showed heterozygous, twelve were
      monoclonal pattern and six were polyclonal pattern. We conclude that carcinoma in
      situ arises from a single cell. In invasive epidermoid carcinoma, most cases were
      monoclonal, although some cases were polyclonal. These suggest that invasive
      carcinoma of the cervix does not always arise from a single cell, but may arise
      from several cells with different mechanisms.

PMID- 9288633
TI  - Characteristics of pain following intracavernous injection of prostaglandin E1.
AB  - The aim of this study was to determine the incidence and characteristics of pain
      following intracavernous injection of prostaglandin E1 (PGE). We injected PGE
      into the cavernous tissues of 156 patients with erectile dysfunction who had
      never previously been injected with PGE. The incidence and characteristics of
      pain after injection were evaluated by the patients' response to a questionnaire.
      The intensity of pain was determined by the degree of impediment to intercourse,
      verbal rating scale (VRS), numerical rating scale (NRS), and visual analogue
      scale (VAS). Patients scoring 'no pain' on the VRS, NRS, and VAS were 11.5%,
      7.7%, and 7.7%, respectively. Overall incidence of pain was 91%. There was 'much'
      or 'very much' impediment to intercourse because of pain in 14 (9.1%) patients.
      The most common kind of pain was 'heavy pain' in 90% of the patients followed by
      'throbbing' in 38%, 'aching' in 21%, 'tightening' in 18%, and 'shooting' in 13%.
      The mean duration of pain was 101.2 +/- 63.7 minutes and it lasted during the
      entire erection period in 71(50.4%) patients. There were significant correlations
      among the degree of impediment to intercourse, VRS, NRS, and VAS scores (all p <
      0.01). However, no association was noted between pain intensity and both erectile
      response to PGE and injected dose. The higher incidence of intracavernous PGE
      induced pain reported here compared to other studies might be related to
      difference in pain thresholds among races. The high incidence of pain but low
      frequency of much impediment to intercourse would be related to the pain
      characteristics as well as the intensity of pain.

PMID- 9288634
TI  - Molecular analysis of hypoxanthine guanine phosphoribosyltransferase (HPRT) gene
      in five Korean families with Lesch-Nyhan syndrome.
AB  - Lesch-Nyhan syndrome is caused by the complete deficiency of hypoxanthine guanine
      phosphoribosyl-transferase (HPRT). By the analysis of genomic DNA and mRNA using
      the polymerase chain reaction (PCR) technique coupled with direct sequencing,
      five independent mutations in HPRT genes have been identified in Korean Lesch
      Nyhan families. Two novel mutations and three previously reported mutations have
      been found in five independent families. Heterozygous carriers were detected in
      all the families, and prenatal diagnosis was carried out in two families.

PMID- 9288636
TI  - The computed tomographic attenuation and the age of subdural hematomas.
AB  - The sequential change in density (attenuation coefficient) of subdural hematomas
      (SDHs) in computed tomography (CT) is important in understanding the pathogenesis
      and evolution of SDHs. We retrospectively investigated the age of SDHs by CT in
      446 cases. We included 30 cases of chronic SDHs, in whom the density was directly
      measured in the CT. The density of acute (within 7 days) SDH was hyperdense in
      98.6%, isodense in 1.1%, and hypodense in 0.3% of the cases. In subacute (8-22
      days) SDHs, it was hypodense in 45.7%, isodense in 42.9%, and hyperdense in
      11.4%. In chronic (over 22 days) SDHs, 86.7% was isodense and only 13.3% was
      hypodense. In hypodense SDHs, 64.0% was the subacute, and 73.2% of the isodense
      SDHs was the chronic one. The mean interval from injury to CT was 0.5 +/- 1.6
      days in hyperdense SDHs, 20.9 +/- 20.7 days in hypodense SDHs, and 54.9 +/- 44.0
      days in isodense SDHs. In 30 cases of chronic SDH, the average density was 38.0
      +/- 6.9 Hounsfield number(H) in 20 approximately 30 days, 43.8 +/- 12.8 H in 31
      approximately 60 days, 51.8 +/- 5.1 H in 61 approximately 90 days, and 44.2 +/-
      8.3 H in over 90 days. The density of acute SDH is usually hyperdense. It becomes
      hypodense within 3 weeks. Then the density progressively increases by the
      repeated microhemorrhage, which is the mechanism of enlargement of chronic SDH.
      The density of chronic SDH increases with time up to 90 days, then decreases
      again after maturation of the neomembrane, which is the mechanism of spontaneous
      resolution.

PMID- 9288635
TI  - CNS innervation of the urinary bladder demonstrated by immunohistochemical study
      for c-fos and pseudorabies virus.
AB  - The aim of the present study is to verify the functional and anatomical neural
      pathways which innervate the urinary bladder in the central nervous system of the
      rat. To identify the functional neural pathway, the urinary bladder was
      stimulated by infusing formalin for 2 h. Then, brain and spinal cord were
      dissected out and immunohistochemistry was done by using anti-c-fos antibody.
      Many c-fos immunoreactive (IR) neurons were identified in the telencephalic
      cortical areas and in several brainstem nuclei, which are known mostly to be
      related with urinary bladder. In the spinal cord, a number of c-fos IR neurons
      were found in the lamina I, IIo, dorsal gray commissure, sacral parasympathetic
      nucleus. To identify the anatomical neural pathway of the urinary bladder,
      Pseudorabies virus (PRV) was injected into the wall of urinary bladder and was
      identified with anti-PRV by using immunohistochemistry. Most PRV labeled neurons
      were found where c-fos IR neurons were identified and few of them were also in
      the areas where c-fos IR neurons were not found, e.g., prefrontal cortex,
      agranular insular cortex, and subfornical organ. In the spinal cord, PRV labeled
      cells were found all over the gray matter. The present study presents
      morphological evidence demonstrating the supraspinal areas are related with the
      neural control of the urinary bladder and most functional neural pathway of the
      urinary bladder is well consistent with the anatomical neural pathway except in
      some telencephalic cortical areas.

PMID- 9288637
TI  - Recurrent herpes zoster myelitis.
AB  - Recurrent zoster myelitis is quite rare. We present a previously healthy 27-year
      old woman who developed recurrent attacks of myelopathy shortly after the
      characteristic skin rashes of herpes zoster. Magnetic resonance imaging studies
      demonstrated each lesion in the spinal cord at the same segments as the skin
      lesions. She had two attacks at opposite sites at the same spinal cord level and
      complete recovery after being treated with intravenous acyclovir. We suspect that
      direct invasion of varicella zoster virus was the cause of recurrent myelopathy
      in our patient.

PMID- 9288638
TI  - Adult T-cell leukemia/lymphoma with features of CD30-positive anaplastic large
      cell lymphoma--a case report.
AB  - We experienced a 58-year-old Korean man with adult T-cell leukemia/lymphoma with
      features of histologically anaplastic large cell lymphoma involving the skin and
      testis. The patient had cutaneous nodules in both extremities and a palpable
      right testicular mass. Right orchiectomy was performed and specimens of removed
      testicle and skin nodules showed immunohistologically anaplastic large cell
      lymphoma with T-cell phenotype, and CD30 antigen was positive. A human T-cell
      lymphotropic virus type 1 (HTLV-1) antibody titer was over 1 : 256 and
      integration of HTLV-1 proviral DNA pX gene was identified in the peripheral blood
      mononuclear cells and lymphoma tissue by polymerase chain reaction. Peripheral
      blood and bone marrow did not show any evidence of characteristic neoplastic T
      cells.

PMID- 9288639
TI  - Mixed hepatoblastoma in an adult--a case report and literature review.
AB  - Hepatoblastoma is thought to originate from embryonal hepatic tissue, and most of
      these tumors occur in children under the age of 2 years. Hepatoblastoma in adults
      is extremely rare, and the prognosis is much worse than the mixed hepatoblastoma
      of childhood. We experienced a case of mixed hepatoblastoma in a 51 year old
      female patient. She had been suffering from a mild pain and a palpable lump in
      the epigastric area. Serum AFP was 43,850 ng/ml. Computerized tomography and
      selective abdominal angiography showed a large low-density mass. With a suspicion
      of hepatocellular carcinoma of the left lobe, a left lateral segmentectomy was
      performed. The external surface showed a huge protruding mass and the capsule was
      previously ruptured. On section, the tumor was a 11 x 7 cm sized expanding mass
      which had a variegated surface composed of yellow-white friable tissue with
      multifocal hemorrhagic areas. Microscopic examination revealed a tumor consisted
      of epithelial and mesenchymal elements. The mesenchymal cells were spindle in
      shape and proliferated over the whole tumor with focal osteosarcomatous
      differentiation. The epithelial components showed well-differentiated
      hepatocellular carcinoma-like areas, poorly differentiated acinar or tubular
      structures.

PMID- 9288640
TI  - Adrenal carcinosarcoma--a case report.
AB  - Carcinosarcoma of the adrenal gland is an extremely rare variant of
      adrenocortical carcinoma, characterized by a biphasic pattern of carcinoma and
      sarcoma-like components. We report a case of adrenal carcinosarcoma occurring in
      a 61-year-old Korean man who presented with right flank pain of one month
      duration radiating to the back and right iliac crest. The tumor measured 12 x 12
      x 7 cm and adhered to the liver and right upper pole of the kidney. The
      carcinomatous component of the tumor showed polygonal cells in a broad
      anastomosing trabecular pattern with delicate slit-like vascular channels; the
      sarcomatous component showed uniform spindled cells in a fascicular pattern. Both
      the carcinomatous and sarcomatous portions of the tumor were positive for pan
      cytokeratin, and vimentin stained only the sarcomatous areas.

PMID- 9288641
TI  - Cerebral leiomyoma in a child.
AB  - A case of primary cerebral leiomyoma in a 12 year-old boy with unique clinical
      features is described. He presented with fever, and the magnetic resonance
      imaging demonstrated a well demarcated mass in the subcortical white matter of
      the right temporal lobe. The mass showed low signal intensity on T1-weighted
      images and high signal intensity on T2-weighted images with a strong homogeneous
      gadolinium-DTPA enhancement. The mass was removed in toto and was composed of
      fasciculating, monotonous oval to spindle cells which had both
      immunohistochemical and ultrastructural features of primitive smooth muscle
      differentiation. The patient is free of recurrence during the follow-up period of
      56 months. Detailed clinicopathologic findings are discussed.

PMID- 9288642
TI  - Improving stereological estimates for the volume of structures identified in
      three-dimensional arrays of spatial data.
AB  - Investigators frequently measure the volumes of anatomic structures. These
      volumes can answer important scientific questions such as whether a structure
      differs between two groups, which structures a disease affects, or how the size
      of a structure relates to its function. Magnetic resonance (MR) imaging, X-ray
      computed tomography and confocal microscopy are used more and more frequently in
      anatomic studies; each yields information that is spatially organized as a three
      dimensional array. We describe how to improve an efficient stereological
      technique for estimating the volumes of structures that are identifiable in these
      arrays. As an example, we apply the technique to measuring brain volumes by MR
      imaging. We then show how the results of the technique may be used for solving a
      typical problem in experimental design. This technique is applicable to a wide
      range of experimental problems. We discuss its limitations and offer some
      suggestions and observations relating to its use.

PMID- 9288645
TI  - Semithin cryosections as a tool to perform high resolution immunofluorescence and
      in situ hybridization analysis of the nervous tissue: a study in the supraoptic
      nucleus.
AB  - Immunofluorescence and fluorescence in in situ hybridization represent powerful
      approaches to correlate biochemical and molecular data with the structural
      organization of cells and tissues. However, the analysis of tissues by
      fluorescence microscopy is limited by the fact that most methods currently used
      to preserve the morphological integrity of sectioned samples at high resolution
      do not allow access of the labeled probes to the target molecules. Here we have
      made use of semithin cryosections obtained from rat supraoptic nucleus to perform
      immunofluorescence with antibodies directed against cytoplasmic and nuclear
      antigens, as well as fluorescence in situ hybridization with antisense
      oligonucleotide probes complementary to the poly(A) tail of mRNA and to specific
      mRNAs. In addition, DNA was visualized by incubation of sections with digoxigenin
      labeled nucleotides in the presence of Escherichia coli DNA polymerase I. The
      high resolution of this DNA staining in combination with immunolabeling for
      nuclear antigens provides a powerful tool to analyze the structural and
      functional compartmentalization of neuronal cell nuclei. The major conclusion
      from this study is that performing fluorescence microscopy on 1 micron-thick
      cryosections provides an important tool to accurately localize proteins, DNA and
      RNA within nervous tissue in general and particularly in the model of supraoptic
      nucleus. Moreover, the cryosectioning technique appears particularly suited to
      the study of the localization of specific mRNA species in the neuronal cytoplasm
      and represents a useful approach to addressing the functional significance of
      mRNA localization in protein targeting.

PMID- 9288643
TI  - Empirical assessment of synapse numbers in primate neocortex.
AB  - Reliable methods are needed to assess the impact of synaptic loss on brain
      function. In this empirical study we demonstrate a novel and efficient method
      using immunocytochemistry (ICC) and modern stereological techniques to quantify
      synapses in neocortex of adult primates (Macaca fascicularis). Systematic-uniform
      random sections through forebrain from two 10-year-old monkeys were immunostained
      for estimation of synaptophysin-immunoreactive (synaptophysin-IR) presynaptic
      boutons (synapses). Adjacent sections were stained with cresyl violet for
      estimation of total number of neuronal cell bodies. The unbiased Cavalieri method
      was used to estimate total forebrain and neocortical volumes to a high level of
      precision (coefficient of error (CE) < or = 0.10)). Synapse-to-neuron ratios
      varied from 860 in frontal cortex to 2300 in parietal-temporal cortex. The
      combination of Cavalieri and optical disector methods provided a direct means of
      estimating approximately 1.25 trillion (x 10(12)) total synaptophysin
      immunopositive boutons and approximately 1.01 billion (x 10(9)) cell bodies in
      neocortex, with low CEs (0.12). Time required to make precise estimates of total
      neocortical and forebrain volumes and total numbers of synapses and neurons in
      neocortex was approximately 2-3 h per case from stained sections. The approach is
      a direct and efficient technique to quantify total synapse and neuron numbers
      within a defined brain structure.

PMID- 9288644
TI  - Confocal imaging of intracellular chloride in living brain slices: measurement of
      GABAA receptor activity.
AB  - We have developed a method using UV laser-scanning confocal microscopy and the
      fluorescent chloride ion indicator, 6-methoxy-N-ethylquinolinium chloride (MEQ),
      to image GABA-mediated changes in intracellular chloride (Cli-) in individual
      neurons of the rat acute brain slice. After bath-loading slices with the cell
      permeant form (reduced) of MEQ, there was intense fluorescence within neurons of
      diverse morphologies in the hippocampus, neocortex and cerebellum. MEQ
      fluorescence localized to the cytosolic compartment of both the somata and
      proximal dendrites. MEQ fluorescence was calibrated using the ionophores
      nigericin and tributyltin in the presence of varying extracellular Cl-
      concentrations. Neuronal MEQ fluorescence was inversely related to intracellular
      Cl-, with a Stern-Volmer constant of 16 M-1 (50% quench by 61 mM Cl-).
      Application of GABA in the perfusate produced a concentration-dependent decrease
      in MEQ fluorescence (EC50 = 40 microM) that was blocked in the presence of the Cl
      channel antagonist, picrotoxin. Bath perfusion of hippocampal slices with
      modulators of the GABAA receptor, pentobarbital and diazepam, potentiated the
      GABA-mediated response by 85 and 44%, respectively. A regional comparison
      identified larger GABA responses for both cerebellar Purkinje and granule cells
      relative to pyramidal neurons of the hippocampus and neocortex and to hippocampal
      interneurons. Pressure ejection of the GABAA agonist, muscimol (40 microM), from
      a micropipet onto individual hippocampal neurons allowed the measurement of rapid
      responses (1-5 s), compared to those obtained with bath application. Thus,
      optical imaging of [Cl-]i using MEQ and UV-laser-scanning confocal microscopy
      provides investigators with a new method to study GABAA pharmacology in
      neighboring neurons and perhaps even in the soma versus dendrites simultaneously,
      within living brain slices.

PMID- 9288646
TI  - AVERAGE: a Windows program for automated analysis of event related cerebral blood
      flow.
AB  - Functional transcranial Doppler sonography (fTCD) is used to measure changes in
      brain perfusion during different states of brain activity by evaluating flow
      velocities within the major brain arteries. We developed a computer program
      called AVERAGE which can be used with various TCD devices and allows for subtle
      quantitative off-line analysis of Doppler flow signals. AVERAGE supports data
      transformation, heart beat analysis, noise reduction, trigger signal and marker
      modification, artifact analysis and artifact rejection, as well as data
      reduction. Perfusion differences and their time course within two different
      arteries can be analyzed by parametric and non parametric statistical methods.
      This is important, for instance, in studies on hemispherical dominance during
      mental task processing. Each data processing step is supported by graphical
      output. If investigated bilaterally with interhemispheric analysis even minimal
      activations can reliably be detected and quantified with a sensitivity known from
      positron emission tomography approaches.

PMID- 9288647
TI  - A chronic model to simultaneously measure intracranial pressure, cerebral blood
      flow, and study the pial microvasculature.
AB  - In an effort to study changes in cerebral blood flow (CBF), intracranial pressure
      (ICP) and intracranial compliance (ICC) simultaneously, we have developed a
      chronic model in rats using a pial window crown with two ports. This model can
      also be used to study vasoreactivity of pial vessels. Female Sprague-Dawley rats
      weighing between 225-250 g underwent placement of cranial chamber with dual ports
      under pentobarbital anesthesia. To test the utility of this technique 45 groups
      of rats were studied. Group 1 consisted of control animals. Group 2 consisted of
      rats undergoing 15 min of global cerebral ischemia. Rats in group 3 were
      evaluated for changes in vessel diameter and ICP after adenosine injection. In
      group 4 leukocyte/endothelial interactions were evaluated. These groups
      demonstrate the ability of this model to monitor CBF, ICP, ICC and pial vessel
      architecture in chronic rat experiments.

PMID- 9288648
TI  - Injection of dye into neurones in rat and human post-mortem brain, in combination
      with acetylcholinesterase histochemistry: permanent preparations.
AB  - We describe a protocol for the intracellular injection of dye into neurones in
      thick sections of fixed, post-mortem rat and human brain tissue. To render the
      sections with the intracellularly injected neurones permanent, they are sectioned
      again, and the resulting subsections are either immunocytochemically treated or
      stained histochemically for acetylcholinesterase (AChE) activity. The resultant
      preparations can be stored at room temperature for prolonged periods. Background
      staining produced by accumulation of erythrocytes in blood vessels is greatly
      reduced or virtually eliminated by exposure of the sections to ultraviolet
      radiation prior to the intracellular injection. The pattern of AChE staining is
      not affected by this procedure. This ability to stain sections according to a
      histochemical AChE procedure after the intracellular injection of dyes into
      striatal neurons opens the possibility to study the relationship of neuronal
      dendritic trees with the striosome/matrix compartmental boundaries in post-mortem
      (human) brain tissue of Huntington's disease patients.

PMID- 9288649
TI  - Preferential glial cell attachment to microcontact printed surfaces.
AB  - Microcontact printing is introduced as a method for fabricating test surfaces for
      attachment of cells to chemically patterned silicon surfaces. Tests with
      astroglial cells indicate that cells attach to microcontact printed surfaces
      similarly to surfaces produced by traditional photolithographic methods.
      Astroglial cells attach selectively to 50 microns wide bars of N1[3
      (Trimethoxysilyl)propyl]diethylenetriamine (DETA) self-assembled monolayers
      (SAMs) on surfaces prepared using variable width spaces generated from
      microcontact printing with octadecyltrichlorosilane (OTS) as the ink. Our results
      demonstrate that microcontact printing provides an effective and rapid method for
      routine production of patterned self-assembled monolayers that can be used for
      directing cell attachment and studying cell morphology.

PMID- 9288650
TI  - Potential misconceptions in dopamine transporter assays arising from the binding
      of [125I]RTI-121 to filters: effect of ions and cocaine.
AB  - Binding of the cocaine analog 3 beta-(4-[125I]iodophenyl)tropane-2 beta
      carboxylic acid isopropyl ester ([125I]RTI-121) to filters was studied in order
      to assess its contribution to labeling dopamine transporters on rat striatal
      synaptosomal membranes in filtration assays. Filter binding (FB) decreased with
      increasing Na+. Cocaine (30 and 100 microM) substantially reduced the FB at low
      Na+ with much less of an effect at higher Na+. Similar results were observed with
      K+. At 10 mM Na+, RTI-121 (1 microM) displaced the FB to the same degree as
      cocaine (100 microM); mazindol (10 microM), BTCP (1 microM), and dopamine (1 mM)
      did so to a lesser degree; and GBR12935 (1 microM) did not. If the specific
      binding was calculated without deducting the FB displaced with cocaine (DFB), the
      DFB accounted for 15-19% of the 'specific binding' at 10 mM Na+ in the assay.
      This additional binding population resulted in an upward curvilinear Scatchard
      plot and incorrect estimation of equilibrium binding parameters and ion
      potencies. At 10 mM Na+, without deduction of DFB, the high-affinity component
      had a Kd of 3.4 nM and Bmax of 2.4 pmol/mg protein, and the respective values for
      the low-affinity component were 84 nM and 16 pmol/mg protein; when DFB was
      deducted, one component was observed with a Kd of 4.4 nM and Bmax of 3.3 pmol/mg
      protein. The presence of higher Na+ in the assay diminished these artifacts.
      Thus, at 150 mM Na+, without deduction of DFB, there was one binding component
      with a Kd of 3.9 nM and Bmax of 4.6 pmol/mg protein; these values became 3.3 nM
      and 3.8 pmol/mg protein when DFB was deducted.

PMID- 9288651
TI  - Performance of real time separation of multi-neuron recordings with a DSP32C
      microprocessor.
AB  - The performance of a method for sorting of waveforms in multi-neuron data
      (Gadicke and Albus, 1995) is evaluated by using artificial spike patterns
      generated by the computer and by adding to these spikes noise or free running
      sine waves of varying frequency and amplitude to simulate EEG-waves. The DSP32C
      is capable of continuously processing spikes at 183.106 Hz. In addition to real
      time sorting the DSP32C also performs a running average of the spikes sorted into
      each class and transfers data to the host computer. The ability of the system to
      analyse burst of activity is determined by the FIFO memory buffer (2048 samples,
      or 32.768 ms at 62.5 kHz sampling rate). Adding a 50 Hz sine wave discrimination
      worked correctly with sine wave amplitudes of up to 2.5 times that of the
      smallest spike. Combining spikes with noise revealed errors of inclusion and/or
      exclusion of less than 0.1% provided the models spikes were determined from
      noiseless spikes and the spike threshold was set above the noise peak level. When
      noisy spikes were used to define model spikes about 4% of the smallest amplitude
      spikes (signal to noise ratio 3.3) were incorrectly classified. For higher
      amplitude spikes (signal to noise ratio > or = 5) the classification error was on
      average less than 1%. The artificial patterns used for performance testing are
      exactly defined and could be used to standardize the comparison between different
      sorting techniques.

PMID- 9288652
TI  - Recording the slow potentials evoked by odors in the olfactory mucosa of awake
      animals.
AB  - The aim of this report is to expose several improvements which are essential for
      obtaining good recordings from the basal side of the olfactory mucosa of awake
      rats with Ag-AgCl electrodes implanted through holes drilled in the roof of the
      nasal bone. In a first step, we present how this minimally invasive method was
      developed and validated in anesthetized rats. We insist particularly on several
      important points such as the size and form of the electrode tip, the careful
      deposit of silver chloride on this tip or the location of the implanting site.
      Then we demonstrate that the recorded signals have the characteristics of an
      electro-olfactogram (EOG), i.e that they have a local origin, that they change
      with odors and concentrations, and that they do not appear during pure air
      delivery, nor after ipsilateral nostril closure. Lastly we show that this method
      was successfully utilized in awake rats. In provided data demonstrating the
      rhythmicity of EOGs in freely-breathing animals and allowed us to study their
      relationships with respiration.

PMID- 9288653
TI  - Use of cell ELISA for the screening of neurotrophic activities on minor cell
      populations in retinal monolayer cultures.
AB  - In this study we describe a large-scale screening cell ELISA protocol which is
      suitable for the characterization of exogenic factor effects in mixed central
      nervous system (CNS) culture. The main novelty of the assay is that it permits
      the measurement of cellular responses in populations comprising as little as 2-4%
      of the total cell number. For standardization of the assay, we employed
      antibodies against opsin and microtubule-associated protein (MAP2) which label
      distinct retinal cell classes. Embryonic chick retinal neurons were grown in
      microtiter plates and directly processed for detection of antibody binding on the
      same plate. Binding of the antibodies was saturable and the ELISA signal was
      proportional to the number of immunoreactive cells comprising 2-4% and 16% of the
      total cell number with opsin and MAP2 antibodies, respectively. A minimum of 2000
      opsin-positive cells could be reliably determined. Using our cell ELISA protocol,
      we demonstrate a developmental increase of both cell markers which reflected an
      increase in the number of opsin-positive cells but an enhanced expression per
      cell in the case of MAP2. We also show that growth-promoting activity-the
      presumed chick ciliary neurotrophic factor (CNTF)-stimulated the expression of
      opsin in retinal cultures (EC50; 2.3 pM) and that a corresponding activity is
      specifically expressed in the developing retina. Our results show that the cell
      ELISA protocol allows the rapid screening for distinct, low-percentage cell
      populations responding to exogenous factors in mixed CNS cultures.

PMID- 9288654
TI  - Release of endogenous glutamate and gamma-aminobutyric acid from rat striatal
      tissue slices measured by an improved method of high performance liquid
      chromatography with electrochemical detection.
AB  - The release of endogenous glutamate and gamma-aminobutyric acid (GABA) from rat
      brain tissue slices was studied using a tissue slice assay in which detectable
      amounts of the amino acids were released from 1-2 mg of tissue. An improved
      method of high performance liquid chromatography (HPLC) with electrochemical
      detection was employed to measure both glutamate and GABA after derivatization
      with o-phthalaldehyde and sulfide in a single isocratic HPLC analysis. The non
      endogenous amino acid, homoglutamine, was used as an internal standard in
      verifying the consistent derivatization of amino acids and in quantifying amounts
      of glutamate and GABA released from the caudate-putamen tissue. The derivatized
      amino acids (1-30 pmol) were detected as chromatographic peaks eluting at
      baseline level and free of significant interfering co-eluates in a 25-30 min
      analysis time.

PMID- 9288655
TI  - Making the female condom a "reality" for adolescents.
AB  - Alarming rates of pregnancy, sexually transmitted diseases, and human
      immunodeficiency virus infection among adolescents point to the need for
      expanding contraceptive options for adolescents. The female condom-a female
      controlled barrier method that protects both partners from sexually transmitted
      diseases-marks an important breakthrough in contraceptive technology. This report
      reviews current research on the efficacy and acceptability of the female condom
      and considers the feasibility of its use in the adolescent population.
      Specifically, the authors first consider the factors that affect teenage condom
      (and other contraceptive) use (efficacy, cost and availability, and
      acceptability) and then apply the mechanics of the female condom to these issues.
      Based on this analysis, recommendations for future steps to be taken by
      researchers, adolescent health practitioners, and the manufacturer of the female
      condom are presented.

PMID- 9288657
TI  - Hyperlipidemia and presence of thyroid autoantibodies in girls with Turner's
      syndrome or mosaic variance.
AB  - OBJECTIVE: The investigation of differences in the medical status between girls
      with Turner's syndrome or mosaic variance and healthy girls of the same age. In
      addition, the existence of differences between those persons with full Turner's
      syndrome and those with mosaic variance were examined. The influence of the
      treatment was also of concern because a number of the subjects in the study group
      were being treated with hormones (estrogen and progestin). Investigation
      concerned cardiovascular abnormalities, bone age, and lipid and hormonal profiles
      of the participating persons. PARTICIPANTS: Girls came to the hospital with
      problems in their menstrual cycles. Genetic control (karyotyping) took place.
      Each patient with symptoms of Turner's syndrome or mosaic variance was included
      in the study group. Every third patient with no symptoms of the syndromes and
      near the same age were included in the control group. METHODS: Stratification was
      made according to the body mass index of the participating persons. Nonparametric
      tests were used for the analysis. RESULTS: Differences were detected in the
      levels of cholesterol, low-density lipoproteins (LDLs), high-density lipoproteins
      (HDLs), and triglycerides, and were increased in the study group. Presence of
      thyroid autoantibodies, antithyreo-globulin-antibodies (AASTs) and
      antimicrosomatic antibodies (AASMs), was observed in the study group. In
      addition, differences were observed in HDL levels between persons with full
      Turner's syndrome and those with mosaic variance. Finally, significant difference
      was observed in the level of triglycerides and in the presence of AASTs and AASMs
      in treated and untreated persons with mosaic variance. CONCLUSIONS: Metabolic,
      genetic, eating or autoimmune mechanisms are suspected.

PMID- 9288656
TI  - Clinical, endocrinologic, and ultrasonographic features of polycystic ovary
      syndrome in Singaporean adolescents.
AB  - The study sought to evaluate the clinical, endocrinologic, and ultrasonographic
      features in 150 Singaporean adolescent girls with polycystic ovary syndrome
      (PCOS) before and after treatment, which was composed primarily of a combined
      hormone therapy of estrogen and cyproterone acetate. The patients' ages ranged
      from 12 to 22 years with the majority between 15 and 18 years of age. Most of
      these girls were seen between their third and fifth gynecologic year. A
      considerable proportion of them had matured early, experiencing menarche between
      9 and 12 years of age. Tanner staging was normal except for a greater proportion
      at higher stages for pubic and axillary hair, most likely a reflection of the
      substantial degree of androgenization commonly found in subjects with PCOS. All
      150 patients presented with menstrual disorders including secondary amenorrhea,
      menarche only, anovulatory uterine bleeding, oligomenorrhea, and primary
      amenorrhea. The majority had normal body weight; 10% to 27% were either
      underweight or overweight, respectively. On ultrasound, patients presented with
      enlarged ovaries; enlargement was more pronounced in the right ovary with dense
      stroma and multiple subcapsular cysts. Many subjects had elevated androgen,
      luteinizing hormone (LH), and LH/ follicle-stimulating hormone (FSH) levels.
      Although characteristic of PCOS, FSH levels were either low or normal. Prolactin,
      estradiol, dehydroepiandrosterone sulfate (DHEAS), and androstenedione were
      generally normal. A substantial proportion of the study group had elevated
      cortisol levels. It was noted that adolescent girls with PCOS responded well to
      treatment; more than 60% showed improvement in cycle profiles following at least
      1 year of treatment. Our current opinion is that adolescents with PCOS should be
      managed early, and that treatment should include medical correction of any
      hormonal or body-weight imbalance and include psychologic intervention when
      necessary.

PMID- 9288658
TI  - Follow-up of abnormal Papanicolaou smears in a hospital-based adolescent clinic.
AB  - STUDY OBJECTIVE: To present data on the spectrum of abnormal Papanicolaou (PAP)
      smears in adolescents and to determine factors that influence compliance with
      recommendations to return for repeat PAP smears or for colposcopic examination.
      DESIGN: Retrospective chart review with follow-up telephone calls to patients who
      did not follow recommendations for colposcopy. SETTING: Adolescents receiving
      health care in a hospital-based adolescent clinic. PARTICIPANTS: Patients with
      abnormal PAP smears between July 1, 1994 and June 30, 1995. MAIN OUTCOME
      MEASURES: Compliance with follow-up for abnormal PAP smears including referral to
      the colposcopy clinic, and the results of repeat PAP smears and colposcopy.
      RESULTS: Of 888 adolescents undergoing PAP smear evaluation 119 (13.4%) had an
      abnormal PAP smear during the study year (index PAP). The results of the index
      PAP were 97 (81.5%) atypia and 22 (18.5%) squamous intraepithelial lesion low
      grade (SIL LG). The index PAP was the first abnormal PAP smear for 92 of the
      patients (77%); 27 had one or more previous abnormal PAP smears (18 atypia, 7 SIL
      LG, 2 SIL high grade [HG]), and 13 had been referred for colposcopy in the past.
      For 76 of 92 patients with atypia on index PAP (84%), the index PAP was the first
      abnormal PAP smear. Of these 76 patients, 51 had a second PAP smear: 27 (53%)
      were normal, 13 (25%) atypia, and 11 (22%) SIL LG. Sixty patients were referred
      to the colposcopy clinic, but only 37 actually kept the colposcopy appointment
      despite outreach. The only significant factor for obtaining colposcopy was a
      visit to the Adolescent Clinic after notification of the abnormal PAP smear
      result and before the colposcopy appointment; 79% of those who had a visit
      obtained colposcopy compared with 45% of those who did not have such a visit (p =
      0.007). There were no significant differences by race, insurance status, age, PAP
      smear result, previous referral for colposcopy, or number of reminders with
      compliance with recommendations for repeat PAP smears or colposcopy. CONCLUSIONS:
      Although a sizable proportion of adolescents with abnormal PAP smears have
      significant pathology on repeat PAP smears, adolescents with abnormal PAP smears
      have a high failure rate in keeping appointments for follow-up PAP smears and
      colposcopy. Interventions that target all adolescents with abnormal PAP smears
      need to be designed and tested to aid follow-up.

PMID- 9288659
TI  - Persistence of autonomous ovarian activity after discontinuation of therapy for
      precocious puberty in McCune-Albright syndrome.
AB  - OBJECTIVE: The aim of this study was to evaluate the possibility of persistence
      of autonomous ovarian activity in girls with McCune-Albright syndrome (MAS) after
      withdrawal of medroxyprogesterone therapy administered for precocious puberty.
      DESIGN, SETTING, AND PARTICIPANTS: Five girls with MAS were followed-up 1.2 to
      8.5 years after the end of treatment. The girls underwent luteinizing hormone
      releasing hormone (LH-RH) tests, estradiol (E2) basal measurement, and pelvic
      ultrasound two times in the follow-up period. RESULTS: Menses resumed in four of
      five girls, 1.4 +/- 0.9 years after the end of treatment, at chronologic age of
      11.3 +/- 1.3 years. Cycles for all girls were irregular. Three patients presented
      inadequate E2 levels (from 56 to 320 pg/mL) associated with low or absent
      gonadotropin response to LH-RH tests. The pelvic ultrasound showed ovarian cysts
      at the time of the study. CONCLUSION: These hormonal and ultrasonographic
      findings provide evidence of persistence of autonomous ovarian activity in some
      young women with MAS.

PMID- 9288660
TI  - Sexuality and contraception in adolescents from Barcelona, Spain.
AB  - STUDY OBJECTIVE: To describe the sexual behavior and contraception use among a
      sample of high school and vocational school adolescents in Barcelona, Spain.
      DESIGN: Cross-sectional study. METHODS: A random sample of 3139 students, aged 14
      to 19 years, living in the city of Barcelona, were surveyed by means of an
      anonymous, self-administered questionnaire. SPSS/PC+ was used for statistical
      analysis. Significance criterion was set at 0.01. MAIN RESULTS: 13% of the
      students had previously participated in sexual intercourse; percentages between
      the sexes was equal. Frequency increased with age. Boys had their first
      experience at a significantly earlier age, but girls participated in sexual
      intercourse more often. The majority of adolescents used condoms as their primary
      contraceptive method; seven (3.3%) of the sexually active girls had been
      pregnant, and two (1%) boys had caused their partners to become pregnant.
      CONCLUSIONS: The rate of sexual activity among adolescents in Barcelona is low
      compared with those in both European and American studies. However, a higher rate
      of condom use is observed.

PMID- 9288662
TI  - High sensitivity test for the early diagnosis of gestational hypertension and
      preeclampsia. III. Computation of time-specified tolerance intervals as reference
      for blood pressure excess in the diagnosis of gestational hypertension.
AB  - According to classic embryological testbooks intervillous circulation is
      established early in the first trimester. This process starts with trophoblastic
      invasion of the decidua in which proteolytic enzymes facilitate the penetration
      and erosion of the adjacent maternal capillaries with formation of the lacunae.
      After the lacunar or previllous stage trophoblast invades deeper portions of
      endometrium with belonging spiral arteries. This gradual process finishes with
      direct opening of the spiral arteries in the intervillous space under the fully
      developed placenta. This classic concept of establishment of the intervillous
      circulation was challenged in 1987 and 1988 by the experiments of Hustin and
      Shaaps. The authors believed that blood flow in the intervillous space is absent
      in incompletely development before 12 weeks of gestation. After the introduction
      of the generation of far more sensitive color Doppler devices in the last few
      years, our group and several others reported a positive finding of intervillous
      circulation during the first trimester of pregnancy.

PMID- 9288661
TI  - Conflicting data on intervillous circulation in early pregnancy.
AB  - According to classic embryological textbooks intervillous circulation is
      established early in the first trimester. This process starts with trophoblastic
      invasion of the decidua in which proteolytic enzymes facilitate the penetration
      and erosion of the adjacent maternal capillaries with formation of the lacunae.
      After the lacunar or previllous stage trophoblast invades deeper portions of
      endometrium with belonging spiral arteries. This gradual process finishes with
      direct opening of the spiral arteries in the intervillous space under the fully
      developed placenta. This classic concept of establishment of the intervillous
      circulation was challenged in 1987 and 1988 by the experiments of HUSTIN and
      SHAAPS. The authors believed that blood flow in the intervillous space is absent
      in incompletely development before 12 weeks of gestation. After the introduction
      of the new generation of far more sensitive color Doppler devices in the last few
      years, our group and several others reported a positive finding of intervillous
      circulation during the first trimester of pregnancy.

PMID- 9288663
TI  - High sensitivity test for the early diagnosis of gestational hypertension and
      preeclampsia. IV. Early detection of gestational hypertension and preeclampsia by
      the computation of a hyperbaric index.
AB  - The aims of this study were to examine whether the combined approach of 1)
      establishing tolerance intervals for the circadian variability of blood pressure
      as a function of gestational age, and 2) computing the hyperbaric index by
      comparison of any patient's blood pressure profile (obtained by ambulatory
      monitoring) with the tolerance limits, provides a new highly sensitive test for
      the early detection of gestational hypertension and preeclampsia. We analyzed a
      total of 745 blood pressure series sampled by ambulatory monitoring for about 48
      hours in each of several occasions in 189 women with uncomplicated pregnancies,
      71 with gestational hypertension, and 29 with preeclampsia. After synchronization
      of all data by expressing times of sampling in hours from bed-time, circadian
      tolerance limits were first computed from the normotensive subjects as a function
      of trimester of pregnancy. The hyperbaric index and the percentage time of excess
      were then computed for each individual blood pressure series. The maximum
      hyperbaric index was below 15 mmHg X hour for normotensive pregnant women in all
      trimesters of pregnancy, and mostly above that value for women who subsequently
      developed gestational hypertension or preeclampsia. Sensitivity of the test based
      on the maximum hyperbaric index was 97% for women sampled during the first
      trimester of gestation, and increased up to 100% in the third trimester. The
      positive predictive value was 100% in all trimesters. Moreover, the computation
      of the hyperbaric index provided, on the average, an early identification of
      gestational hypertension or preeclampsia 20 weeks prior to the clinical
      confirmation of the disease. CONCLUSIONS: Ambulatory monitoring of blood pressure
      during gestation provides sensitive endpoints for use in early risk assessment
      and as a guide for establishing preventive interventions. The approach presented
      here represents a simple, reproducible, non-invasive, and highly sensitive test
      for the very early identification of gestational hypertension and preeclampsia.

PMID- 9288664
TI  - Fetal renal hyperechogenicity in pathological pregnancies.
AB  - A relationship was sought between renal hyperechogenicity and the hypoxic state
      of fetuses. 120 pathological pregnancies were examined between the 28th and 36th
      week. All of these women exhibited moderately increased levels of hepatic
      enzymes, 3 of them had a pathological kidney function, and 4 of them displayed
      hyperuricemia during the examination period. The echogenicity of the fetal
      kidneys was examined with Hitachi EUB-450 ultrasound equipment with a 3.5 MHz
      transducer. The kidney (creatinine, urea-N, uric acid, triglyceride, cholsterin)
      and liver (SGOT, SGPT, GGT, bilirubin) functions and plasma electrolytes (Na, K,
      Ca, Cl) of the mothers were also examined and blood was collected from the
      pulsating umbilical artery for determination of the same parameters. After
      delivery, the physical condition of the neonates was followed and their kidneys
      were examined with the same ultrasound equipment within the first 5 days. There
      was a significant correlation between a pathological neonatal clinical outcome
      and the frequency of fetal and hyperechogenicity (chi-square test with Yates
      correction, p < 0.01). The results demonstrate that fetuses exhibiting renal
      hyperechogenicity in pathological pregnancies require particularly careful
      obstetric control and neonatological consultation. It is important that
      hyperechogenic cases be admitted to a perinatal intensive care unit. Fetal renal
      hyperechogenicity is considered to be associated with an enhanced risk of an
      adverse perinatal outcome.

PMID- 9288665
TI  - Hyaline membrane disease (HMD) therapy in Latin America: impact of exogenous
      surfactant administration on newborn survival, morbidity and use of resources.
AB  - Impact of surfactant administration, on neonatal mortality, morbidity and
      resource use, was assayed in a historically controlled study in 19 NICUs from 5
      Latin American countries. Data from clinical records of infants with HMD were
      retrospectively reviewed for the previous 2 years (PRE phase n = 666 cases), and
      prospectively in cases that received surfactant (SURF phase, 348 cases). Birth
      weight stratified relative risk, with 95% confidence interval (RR +/-95% CI) for
      death, in the SURF as compared to the PRE was 0.60 (0.49-0.74), 0.79 (0.68-0.92)
      and 0.82 (0.71-0.94), for days 7, 28 and at discharge, respectively. At all ages
      mortality was significantly lower during SURF. Significant increases were
      observed in the occurrence of pulmonary interstitial emphysema, pulmonary
      hemorrhage, patent ductus arteriosus, bronchopulmonary dysplasia, intrahospital
      infection and necrotizing enterocolitis. Resource use increased significantly. It
      is concluded that the use of surfactant in the region is an important advance,
      and the efficacy of management of the late complications of the very premature
      and labile HMD survivors must increase. More attention should be given to thermal
      regulation, nutrition and management of infection in the survivors, before a more
      marked effect of surfactant can be seen.

PMID- 9288666
TI  - Parathyroid hormone and parathyroid hormone-related peptide in venous umbilical
      cord blood of healthy neonates.
AB  - Objective of this study was to assess the role umbilical cord serum parathyroid
      hormone (PTH), and parathyroid hormone-related peptide (PTH-RP) may play in
      maintaining the maternal-fetal calcium (Ca) gradient. PTH and PTH-RP and total
      and ionized Ca levels were measured in blood samples of 20 neonates immediately
      after birth. Maternal peripheral blood total Ca was measured simultaneously.
      Mothers were free of hypertension, diabetes or Ca disorders. Neonates were
      healthy term babies with Apgar scores of eight or greater at one and at five
      minutes post delivery. PTH was measured using an immunoradiometric double
      antibody assay that recognizes intact PTH (1-84). PTH-RP was measured by an
      immunoradiometric double antibody assay that recognizes only PTH-RP (1-74). There
      was no overlap between the two assays. Ca levels in the neonates were higher than
      those in their mothers (p < 0.01), confirming a maternal-fetal Ca gradient.
      However in 18 out of 20 neonates PTH levels in cord blood were below the
      detection limit (3 pg/ml) and PTH-RP levels also were below detection limit (0.2
      pmol/L). PTH-RP and PTH levels in the other two neonates were 0.5 and 0.6 pmol/L
      (PTH-RP) and 3 pg/ml (PTH) which are in the low normal range for normal adults.
      We conclude that these data do not support a role for either PTH or PTH-RP in
      venous cord blood in maintaining the maternal-fetal Ca gradient. They are,
      however, compatible with a paracrine role for these hormones.

PMID- 9288667
TI  - Parathyroid hormone levels in preterm and term labor.
AB  - This prospective study was undertaken to test the hypothesis that parathyroid
      hormone (PTH) might be involved in preterm or term labor. Four groups of patients
      were formed, 15 patients in each group. The preterm labor group were patients who
      were admitted to our perinatal care unit with preterm labor and unruptured
      membranes (< 35 weeks' gestation). The preterm or term nonlabor control groups
      were patients matched for gestational age, maternal age, and parity, who were not
      in labor. The term labor group were patients matched for maternal age and parity
      who were in active labor. Mean (+/-SD) level of biologically intact PTH was 18.9
      +/- 10.6 pgr/mL, 7.6 +/- 4.7 pgr/mL, 20.8 +/- 10.1 pgr/mL, 13.7 +/- 5.3 pgr/mL in
      preterm labor group, preterm nonlabor group, term labor group, and term nonlabor
      group, respectively (p < 0.05). No statistically significant differences were
      observed in the levels of calcium, phosphorus, magnesium, or albumin. We
      therefore suggest that PTH may have a role in preterm or term labor. The nature
      of its role should be investigated in further studies.

PMID- 9288668
TI  - Digitalization of the mother in treating hydrops fetalis in monochorionic twin
      with Ebstein's anomaly. Case report.
AB  - Hydrops fetalis thought to be due to Ebstein's anomaly was seen at 22 weeks'
      gestation in one of two fetuses with a monochorionic placenta. Hydrops was
      treated with maternal digitalization and resolved by the 28th week of gestation.
      Hydrops did not recur while maternal digitalization continued. A clinical
      diagnosis of twin-to-twin transfusion syndrome required termination of the
      pregnancy at 33 weeks of gestation. The twin with Ebstein's anomaly died 22 hours
      after birth. The other twin survived and was normal at 19 months of age. Thus,
      administration of digitalis to the mother controlled hydrops fetalis in one
      fetus, and ultimately led to the survival of the healthy infant.

PMID- 9288669
TI  - Outward currents in smooth muscle cells isolated from sheep mesenteric
      lymphatics.
AB  - 1. The patch-clamp technique was used to measure membrane currents in isolated
      smooth muscle cells dispersed from sheep mesenteric lymphatics. Depolarizing
      steps positive to -30 mV evoked rapid inward currents followed by noisy outward
      currents. 2. Nifedipine (1 microM) markedly reduced the outward current, while
      Bay K 8644 (1 microM) enhanced it. Up to 90% of the outward current was also
      blocked by iberiotoxin (Kd = 36 nM). 3. Large conductance (304 +/- 15 pS, 7
      cells), Ca(2+)- and voltage-sensitive channels were observed during single
      channel recordings on inside-out patches using symmetrical 140 mM K+ solutions
      (at 37 degrees C). The voltage required for half-maximal activation of the
      channels (V1/2) shifted in the hyperpolarizing direction by 146 mV per 10-fold
      increase in [Ca2+]i. 4. In whole-cell experiments a voltage-dependent outward
      current remained when the Ca(2+)-activated current was blocked with penitrem A
      (100 nM). This current activated at potentials positive to -20 mV and
      demonstrated the phenomenon of voltage-dependent inactivation (V1/2 = -41 +/- 2
      mV, slope factor = 18 +/- 2 mV, 5 cells). 6. Tetraethylammonium (TEA; 30 mM)
      reduced the voltage-dependent current by 75% (Kd = 3.3 mM, 5 cells) while a
      maximal concentration of 4-aminopyridine (4-AP; 10 mM) blocked only 40% of the
      current. TEA alone had as much effect as TEA and 4-AP together, suggesting that
      there are at least two components to the voltage-sensitive K+ current. 7. These
      results suggest that lymphatic smooth muscle cells generate a Ca(2+)-activated
      current, largely mediated by large conductance Ca(2+)-activated K+ channels, and
      several components of voltage-dependent outward current which resemble 'delayed
      rectifier' currents in other smooth muscle preparations.

PMID- 9288670
TI  - Tetrodotoxin-sensitive sodium current in sheep lymphatic smooth muscle.
AB  - 1. Fast inward currents were elicited in freshly isolated sheep lymphatic smooth
      muscle cells by depolarization from a holding potential of -80 mV using the whole
      cell patch-clamp technique. The currents activated at voltages positive to -40 mV
      and peaked at 0 mV. 2. When sodium chloride in the bathing solution was replaced
      isosmotically with choline chloride inward currents were abolished at all
      potentials. 3. These currents were very sensitive to tetrodotoxin (TTX). Peak
      current was almost abolished at 1 microM with half-maximal inhibition at 17 nM.
      4. Examination of the voltage dependence of steady state inactivation showed that
      more than 90% of the current was available at the normal resting potential of
      these cells (-60 mV). 5. The time course of recovery from inactivation was
      studied using a double-pulse protocol and showed that recovery was complete
      within 100 ms with a time constant of recovery of 20 ms. 6. Under current clamp,
      action potentials were elicited by depolarizing current pulses. These had a rapid
      upstroke and a short duration and could be blocked with 1 microM TTX. 7.
      Spontaneous contractions of isolated rings of sheep mesenteric lymphatic vessels
      were abolished or significantly depressed by 1 microM TTX.

PMID- 9288671
TI  - Calcium sparks and excitation-contraction coupling in phospholamban-deficient
      mouse ventricular myocytes.
AB  - 1. We examined [Ca2+]i and L-type Ca2+ channel current (ICa) in single cardiac
      myocytes to determine how the intracellular protein phospholamban (PLB)
      influences excitation-contraction (E-C) coupling in heart. Wild type (WT) and PLB
      deficient (KO) mice were used. Cells were patch clamped in whole-cell mode while
      [Ca2+]i was imaged simultaneously using the Ca2+ indicator fluo-3 and a confocal
      microscope. 2. Although ICa was similar in magnitude, the decay of ICa was faster
      in KO than in WT cells and the [Ca2+]i transient was larger and decayed faster.
      Furthermore, the E-C coupling 'gain' (measured as delta[Ca2+]i/ICa) was larger in
      KO cells than in WT cells. 3. Spontaneous Ca2+ sparks were three times more
      frequent and larger in KO cells than in WT myocytes but, surprisingly, the time
      constants of decay were similar. 4. SR Ca2+ content was significantly greater in
      KO than in WT cells. When the SR Ca2+ content in KO cells was reduced to that in
      WT cells, Ca2+ sparks in these 'modified' (KO') cells decayed faster. E-C
      coupling gain, [Ca2+]i transient amplitude and the kinetics of decay of ICa were
      similar in KO' and WT cells. 5. We conclude that SR Ca2+ content influences (1)
      ICa, (2) the amplitude and kinetics of Ca2+ sparks and [Ca2+]i transients, (3)
      the sensitivity of the RyRs to triggering by [Ca2+]i, (4) the amount of Ca2+
      released, (5) the magnitude of the E-C coupling 'gain' function, and (6) the rate
      of Ca2+ re-uptake by the SR Ca(2+)-ATPase. In KO cells, the larger [Ca2+]i
      transients and Ca2+ sparks speed up ICa inactivation. Finally, we conclude that
      PLB plays an important regulatory role in E-C coupling by modulating SR Ca(2+)
      ATPase activity, which establishes the SR Ca2+ content and consequently
      influences the characteristics of local and global Ca2+ signalling.

PMID- 9288672
TI  - The relationship between cutaneous C fibre type and antidromic vasodilatation in
      the rabbit and the rat.
AB  - 1. Skin blood flow was monitored during antidromic stimulation of identified
      cutaneous C fibres in fine filaments dissected from the saphenous nerve of
      anaesthetized rabbits and rats. The techniques used to monitor skin blood flow
      were laser Doppler perfusion imaging and laser Doppler flowmetry. 2. In the
      rabbit filaments a total of thirty-three C fibres were tested for their ability
      to produce antidromic vasodilatation. The only C fibres found to have vasodilator
      actions were of the polymodal nociceptor afferent class, and fourteen (50%) of
      the twenty-eight polymodal nociceptor units tested were vasoactive. The afferent
      receptive fields of polymodal nociceptor afferents were mapped carefully using
      suprathreshold mechanical stimuli, and there was a good correlation between
      afferent receptive field area and area of vasodilatation. 3. In the rat, eleven
      of the fifty-four C fibres antidromically stimulated had vasodilator actions. All
      eleven vasoactive C fibres were nociceptive and comprised seven polymodal
      nociceptor units, two heat nociceptor units and two incompletely classified
      nociceptor units. The area of increased blood flow was always coincident with the
      afferent field of the stimulated unit. 4. In the rat the vasodilator units were
      not evenly distributed over the saphenous nerve receptive field. Nine of the
      eleven vasoactive C fibres had receptive fields located on the foot or the
      digits, and only two were on the ankle or lower leg. Overall, the population of
      nociceptive C fibres was evenly distributed over the saphenous nerve receptive
      field. 5. In both the rabbit and the rat, a subclass of polymodal nociceptor
      afferents form the majority of the vasoactive units and will make the main
      contribution to axon reflex flare and other neurogenic inflammatory responses
      involving vasodilatation. The vasoactive polymodal nociceptor units tend to have
      relatively low mechanical sensitivity, although they have typical heat
      thresholds. In the rat heat nociceptor units also have vasodilator actions.
      However, such heat nociceptor units form a minor functional class of afferent C
      fibre in the rat saphenous nerve, and are not found in the rabbit saphenous
      nerve. 6. The findings from this study in the rabbit and the rat are compared
      with the situation in pig skin. The close relationship between afferent receptive
      field area and spread of flare across species is noted, and the way these
      measures increase with body size is discussed.

PMID- 9288673
TI  - Selective enhancement of the slow component of delayed rectifier K+ current in
      guinea-pig atrial cells by external ATP.
AB  - 1. The effects of external ATP on the rapidly and slowly activating components
      (IKr and IKs, respectively) of the delayed rectifier K+ current (IK) in guinea
      pig atrial myocytes were determined using the whole-cell configuration of the
      patch-clamp technique. 2. An envelope of tails test was conducted by applying
      depolarizing pulses to +40 mV from a holding potential of -40 mV for various
      durations between 50 ms and 2 s under control conditions and during exposure to
      50 microM ATP. The ATP-induced IK, obtained by digital subtraction, exhibited a
      constant ratio (0.37) of the tail current to time-dependent current, regardless
      of the pulse duration. This current ratio was compatible with the predicted ratio
      of the driving force at +40 and -40 mV for a non-rectifying K+ conductance,
      suggesting that the ATP-induced IK is due primarily to IKs. 3. The amplitude of
      IKr isolated from the IK enhanced by ATP, determined as an E-4031 (5 microM)
      sensitive current, was similar to the control magnitude of IKr, thus showing that
      external ATP did not cause an increase in IKr. 4. The voltage-dependent
      activation of the ATP-induced IK during 500 ms depolarizing test pulses could be
      described by a Boltzmann equation with a half-activation voltage (V1/2) of 11.5
      mV and slope factor (k) of 12.0 mV, which were close to those of IKs (V1/2 of
      12.1 mV and k of 12.3 mV), determined as an E-4031-resistant IK, under the same
      isochronal (500 ms) activation conditions. 5. These results provide evidence to
      suggest that extracellular ATP selectively potentiates the slow component of IK
      (IKs), with no measurable effects on IKr, in guinea-pig atrial myocytes.

PMID- 9288676
TI  - Lack of regulation by intracellular Ca2+ of the hyperpolarization-activated
      cation current in rat thalamic neurones.
AB  - 1. The regulation of the hyperpolarization-activated cation current, Ih, in
      thalamocortical neurones by intracellular calcium ions has been implemented in a
      number of mathematical models on the waxing and waning behaviour of synchronized
      rhythmic activity in thalamocortical circuits. In the present study, the Ca2+
      dependence of Ih in thalamocortical neurones was experimentally investigated by
      combining Ca2+ imaging and patch-clamp techniques in the ventrobasal thalamic
      complex (VB) in vitro. 2. Properties of Ih were analysed before and during
      rhythmic stimulation of Ca2+ entry by trains of depolarizing voltage pulses.
      Despite a significant increase in intracellular Ca2+ concentration ([Ca2+]i) from
      resting levels of 74 +/- 23 nM to 251 +/- 78 nM upon rhythmic stimulation,
      significant differences in the voltage dependence of Ih activation did not occur
      (half-maximal activation at -86.4 +/- 1.3 mV vs. -85.2 +/- 2.9 mV; slope of the
      activation curve, 11.2 +/- 2.4 mV vs. 12.5 +/- 2.5 mV). Recording of Ih with
      predefined values of [Ca2+]i (13.2 nM or 10.01 microM in the patch pipette)
      revealed no significant differences in the activation curve or the fully
      activated I-V relationship of Ih. 3. In comparison, stimulation of the
      intracellular cyclic adenosine monophosphate (cAMP) pathway induced a
      significantly positive shift in Ih voltage dependence of +5.1 +/- 1.9 mV, with no
      alteration in the fully activated I-V relationship. 4. These data argue against a
      direct regulation of Ih by intracellular Ca2+, and particularly do not support a
      primary role of Ca(2+)-dependent modulation of the Ih channels in the waxing and
      waning of sleep spindle oscillations in thalamocortical neurones.

PMID- 9288675
TI  - Fractional Ca2+ currents through capsaicin- and proton-activated ion channels in
      rat dorsal root ganglion neurones.
AB  - 1. Capsaicin and protons cause excitation and sensitization of primary
      nociceptive afferents. In a subset of dorsal root ganglion (DRG) neurones, which
      probably represent nociceptive neurones, both capsaicin and protons induce slowly
      inactivating non-selective cation currents. Whole-cell as well as single channel
      currents activated by these two stimuli share many biophysical and physiological
      properties in these neurones. This has lead to the suggestion that protons and
      capsaicin might activate the same ion channels. 2. In this study we
      simultaneously measured fluorescence signals and whole-cell currents activated by
      capsaicin or protons in acutely isolated DRG neurones filled with a high
      concentration (1 mM) of the Ca2+ indicator dye fura-2. From these measurements
      the fractional contribution of Ca2+ (Pf; the portion of the whole-cell current
      carried by Ca2+) to capsaicin- and two types of proton-induced (fast and slowly
      inactivating) membrane currents was determined. 3. Capsaicin- and slowly
      inactivating proton-induced currents were accompanied by a change in fluorescence
      that was dependent on the presence of extracellular Ca2+. With 1.6 mM
      extracellular Ca2+ and at a holding potential of -80 mV Pf of capsaicin-induced
      currents (at pH 7.3) was 4.30 +/- 0.17% (mean +/- S.E.M.; no. of experiments, n =
      16) and of slowly inactivating proton-induced currents (at pH 5.1) was 1.65 +/-
      0.11% (n = 17). Pf of fast inactivating proton-induced currents was negligible.
      4. Pf of capsaicin- and slowly inactivating proton-induced currents increased
      with increasing extracellular Ca2+ concentration (0.5-4.8 mM). 5. Pf of both
      current types decreased linearly with decreasing extracellular pH by about 0.7%
      per pH unit over the pH range investigated. When determined at the same
      extracellular pH Pf values were significantly different for the two current types
      at all pH values tested. 6. In summary, our results provide evidence that
      capsaicin and protons activate ion channels which are markedly permeable to Ca2+.
      The fractional contribution of Ca2+, however, was significantly different for
      capsaicin- and slowly inactivating proton-induced currents. This strongly
      suggests that the two stimuli activate different populations of ion channels and
      supports the possibility that Ca2+ influx through these channels may be important
      for Ca(2+)-dependent sensitization of primary nociceptive neurones.

PMID- 9288674
TI  - Differential effects of endothelin-1 on basal and isoprenaline-enhanced Ca2+
      current in guinea-pig ventricular myocytes.
AB  - 1. We examined the effect of endothelin-1 (ET-1) on basal and isoprenaline
      enhanced L-type Ca2+ current (ICa,L) in guinea-pig ventricular myocytes under
      nystatin-perforated patch configuration. 2. ET-1 at concentrations of 1, 5 and 10
      nM had little effect on basal ICa,L. However, ICa,L enhanced by isoprenaline (500
      nM) was significantly attenuated by 5 nM ET-1 by more than 50%. This effect was
      reversed upon washout. ICa,L enhanced by forskolin was also decreased by ET-1. 3.
      The inhibitory effect of ET-1 against isoprenaline was completely blocked by the
      ETA receptor antagonist BQ-123 (1 microM). In myocytes incubated with pertussis
      toxin (PTX, 2 micrograms ml-1) for 5 h, ET-1 did not inhibit isoprenaline
      enhanced ICa,L. 4. Although ET-1 has been shown to activate specific protein
      kinase C (PKC) isoforms, a significant inhibitory effect of ET-1 was maintained
      in the presence of the PKC inhibitor bisindolylmaleimide (20 nM). The nitric
      oxide (NO) donor SIN-1 (10 microM) attenuated but failed to prevent the ET-1
      effect. 5. In summary, our results demonstrate that ET-1 is devoid of any
      significant effects on basal ICa,L. However, it exerts a potent inhibitory effect
      against isoprenaline-enhanced ICa,L. This effect is mediated through ETA
      receptors coupled to PTX-sensitive G-proteins and occurs in the presence of PKC
      inhibition and NO generation.

PMID- 9288677
TI  - Neurotensin inhibition of the hyperpolarization-activated cation current (Ih) in
      the rat substantia nigra pars compacta implicates the protein kinase C pathway.
AB  - 1. Whole-cell patch-clamp recording was performed from principal neurones of the
      substantia nigra pars compacta (SNc). In 66% of these neurones, neurotensin (NT)
      induced, at -60 mV, an inward current associated with an increase in conductance.
      2. Principal neurones displayed, in response to hyperpolarizing voltage steps,
      the voltage-dependent inward cationic current, Ih. This current activated at
      potentials more negative than -65 mV and reached a maximum at -106 +/- 4 mV, with
      a half-activation potential of -86 +/- 3 mV. Its estimated reversal potential was
      -43 +/- 7 mV and its activation curve was fitted with two exponentials. 3. In 41%
      of neurones showing the inward current, NT (0.5 microM) also reversibly reduced
      the amplitude of Ih. The diminution was 48.5 +/- 12% when voltage steps were made
      from -60 to -95 mV. The decrease in Ih resulted from a reduction in the maximal
      current with no change in the voltage dependence of activation. 4. Forskolin (10
      microM), an activator of adenylate cyclase, increased Ih by shifting its
      activation range to more positive potentials, but it did not alter the NT
      inhibition of Ih. 5. The effect of NT was blocked by staurosporine (0.5 microM)
      and by PKC-(19-31) (0.5 microM), a specific protein kinase C (PKC) inhibitor, but
      was unaffected by Walsh's peptide (100 microM), a specific inhibitor of protein
      kinase A. The reduction of Ih was mimicked by 1-oleoyl-2-acetyl-sn-glycerol (0.5
      10 microM), an analogue of diacylglycerol, an endogenous PKC activator. 6. These
      results suggest that the inhibition of Ih by NT involves a phosphorylation
      mechanism that implies activation of PKC.

PMID- 9288679
TI  - Aminergic modulation of glycine release in a spinal network controlling swimming
      in Xenopus laevis.
AB  - 1. Neuromodulators can effect changes in neural network function by strengthening
      or weakening synapses between neurons via presynaptic control of transmitter
      release. We have examined the effects of two biogenic amines on inhibitory
      connections of a spinal rhythm generator in Xenopus tad poles. 2. Glycinergic
      inhibitory potentials occurring mid-cycle in motoneurons during swimming activity
      are reduced by 5-hydroxytryptamine (5-HT; serotonin) and enhanced by
      noradrenaline (NA). These opposing effects on inhibitory synaptic strength are
      mediated presynaptically where 5-HT decreases and NA increases the probability of
      glycine release from inhibitory terminals. 3. The amines also have contrasting
      effects on swimming: 5-HT increased motor burst durations while NA reduced
      swimming frequency. Aminergic modulation of glycinergic transmission may thus
      control fundamental parameters of swimming and force the spinal network to
      generate opposite extremes of its spectrum of possible outputs.

PMID- 9288678
TI  - Peptides homologous to extracellular loop motifs of connexin 43 reversibly
      abolish rhythmic contractile activity in rabbit arteries.
AB  - 1. Phenylephrine (10 microM) evoked rises in tension in isolated rings of
      endothelium-denuded rabbit superior mesenteric artery. These increases consisted
      of a tonic component with superimposed rhythmic activity, the frequency of which
      generally remained constant over time but whose amplitude exhibited cycle-to
      cycle variability. 2. The amplitude, but not the frequency, of the rhythmic
      activity was affected by a series of short peptides possessing sequence homology
      with extracellular loops 1 and 2 of connexin 43 (Cx43). Oscillatory behaviour was
      abolished at concentrations of 100-300 microM (IC50 of 20-30 microM), without
      change in average tone. No synergy was evident between peptides corresponding to
      the extracellular loops, and cytoplasmic loop peptides were biologically
      inactive. 3. The putative gap junction inhibitor heptanol mimicked the action of
      the extracellular loop peptides and abolished rhythmic activity at concentrations
      of 100-300 microM without effects on frequency. However, in marked contrast to
      the peptides, heptanol completely inhibited the contraction evoked by
      phenylephrine (IC50, 283 +/- 28 microM). 4. The presence of mRNA encoding Cx32,
      Cx40 and Cx43 was detected in the rabbit superior mesenteric artery by reverse
      transcriptase-polymerase chain reaction. Western blot analysis showed that Cx43
      was the major connexin in the endothelium-denuded vessel wall. 5. We conclude
      that intercellular communication between vascular smooth muscle cells via gap
      junctions is essential for synchronized rhythmic activity in isolated arterial
      tissue, whereas tonic force development appears to be independent of cell-cell
      coupling. The molecular specificity of the peptide probes employed in the study
      suggests that the smooth muscle relaxant effects of heptanol may be non-specific
      and unrelated to inhibition of gap junctional communication.

PMID- 9288680
TI  - Stimulation of alpha 1-adrenoceptors and protein kinase C-mediated activation of
      ecto-5'-nucleotidase in rat hearts in vivo.
AB  - 1. To determine whether protein kinase C (PKC)-mediated activation of ecto-5'
      nucleotidase would increase interstitial adenosine concentrations in the rat
      heart in vivo, we made use of the microdialysis technique and a flexibly mounted
      probe, which was implanted in the left ventricular myocardium and perfused with
      Tyrode solution. 2. The baseline level of dialysate adenosine was 0.51 +/- 0.09
      microM (n = 16). Perfusion of adenosine 5'-monophosphate (AMP, 100 microM)
      through the probe increased the dialysate adenosine concentration markedly to
      9.25 +/- 0.46 microM (n = 15). alpha, beta-Methyleneadenosine 5'-diphosphate
      (AOPCP, 100 microM), an inhibitor of ecto-5'-nucleotidase, abolished the AMP
      induced increase in dialysate adenosine, but did not affect the baseline level of
      adenosine. These observations suggest that the dialysate adenosine obtained
      during the perfusion with AMP, but not the baseline levels of adenosine,
      originated from the dephosphorylation of AMP by ecto-5'-nucleotidase. Thus, the
      level of adenosine measured during AMP perfusion gives an index of the activity
      of ecto-5'-nucleotidase in the tissue. 3. Noradrenaline (10 microM) increased the
      adenosine concentration measured in the presence of 100 microM AMP (i.e. the
      activity of ecto-5'-nucleotidase) by 38.7 +/- 9.6% (n = 5, P < 0.05), an increase
      which was inhibited by an antagonist of the alpha 1-adrenoceptor (prazosin, 50
      microM) or of PKC (chelerythrine, 10 microM). Further application of either the
      alpha 1-adrenoceptor agonist methoxamine (100 microM) or the diacylglycerol
      analogue 1,2-dioctanoyl-sn-glycerol (DOG, 100 microM) also increased the
      adenosine concentration by 35.1 +/- 10.0% (n = 6, P < 0.05) or 40.6 +/- 8.3% (n =
      5, P < 0.05), respectively. 4. The presence of okadaic acid (50 microM), an
      inhibitor of protein phosphatase, enhanced the noradrenaline-induced increase in
      adenosine concentration by 112.4 +/- 35.9% (n = 4, P < 0.05), to a level
      significantly (P < 0.05) greater than the increase caused by noradrenaline alone
      (38.7 +/- 9.6%). 5. These data provide the first evidence that alpha 1
      adrenoceptor stimulation and the subsequent activation of PKC can increase
      adenosine concentrations in interstitial spaces of ventricular muscle in vivo,
      through activation of endogenous ecto-5'-nucleotidase.

PMID- 9288681
TI  - Regulation of quantal secretion by neurotrophic factors at developing motoneurons
      in Xenopus cell cultures.
AB  - 1. The ability of different neurotrophic factors to maintain and regulate
      synaptic function at the developing motoneuron was studied in Xenopus nerve
      muscle co-cultures. Spontaneous synaptic currents (SSCs) were measured by using
      whole-cell voltage-clamped myocytes. 2. Compared with natural synapses,
      motoneurons without contact on a myocyte (naive neurons) released ACh in smaller
      quantal packets, the amplitude being inversely proportional to the days in
      culture. The mean SSC amplitudes of naive neurons, which were measured by
      manipulating a myoball into contact with the myocyte-free nerve terminals to form
      a manipulated synapse, were 99.5 +/- 6.7 and 48.2 +/- 1.9 pA for day-1 and day-3
      cultures, respectively. 3. Chronic treatment of day-1 cultures with brain-derived
      neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4), ciliary
      neurotrophic factor (CNTF) or glial cell line-derived neurotrophic factor (GDNF)
      for 2 days, increased the ACh quantal size of naive motoneurons in a
      concentration-dependent manner, whereas insulin-like growth factor-1 (IGF-1) and
      basic fibroblast growth factor (bFGF) had no effect, even at high concentrations.
      4. The interaction of various neurotrophic factors was examined, using
      concentrations that gave maximal effects. Combination of CNTF plus BDNF or CNTF
      plus NT-3 had synergistic effects in potentiating SSC amplitude of the
      manipulated synapse of naive neurons, whereas NT-3 plus BDNF, NT-3 plus GDNF,
      BDNF plus GDNF or CNTF plus GDNF had no synergistic action. 5. Chronic treatment
      with d-tubocurarine for 2 days resulted in a reduction of the quantal size of
      natural synapses. Concomitant treatment with BDNF, NT-3, GDNF, CNTF but not bFGF
      or IGF-1, reconstituted the SSC amplitude. 6. Taken together, these findings
      suggest that BDNF, NT-3, NT-4, CNTF and GDNF may regulate and maintain the
      synaptic function of developing motoneurons, and different neurotrophic factors
      utilizing distinct signalling mechanisms may have synergistic actions.

PMID- 9288682
TI  - The biphasic force-velocity relationship in frog muscle fibres and its evaluation
      in terms of cross-bridge function.
AB  - 1. The relationship between force and velocity of shortening was studied during
      fused tetani of single fibres isolated from the anterior tibialis muscle of Rana
      temporaria (1.5-3.3 degrees C; sarcomere length, 2.20 microns). Stiffness was
      measured as the change in force that occurred in response to a 4 kHz length
      oscillation of the fibre. 2. The results confirmed the existence of two distinct
      curvatures of the force-velocity relationship located on either side of a
      breakpoint in the high-force, low-velocity range. Reduction of the isometric
      force (P0) to 83.4 +/- 1.7% (mean +/- S.E.M., n = 5) of the control value by
      dantrolene did not affect the relative shape of the force-velocity relationship.
      The breakpoint between the two curvatures was located at 75.9 +/- 0.9% of P0 and
      11.4 +/- 0.6% of maximum velocity of shortening (Vmax) in control Ringer solution
      and at 75.6 +/- 0.7% of P0 and 12.2 +/- 0.7% of Vmax in the presence of
      dantrolene. These results provide evidence that the transition between the two
      curvatures of the force-velocity relationship is primarily related to the speed
      of shortening, not to the actual force within the fibre. 3. The instantaneous
      stiffness varied with the speed of shortening forming a biphasic relationship
      with a breakpoint near 0.15 Vmax and 0.8 P0, respectively. The force/stiffness
      ratio (probably reflecting the average force per cross-bridge), increased with
      force during shortening. The increase of the force/stiffness ratio with force was
      less steep at forces exceeding 0.8 P0 than below this point. 4. A four-state
      cross-bridge model (described in the Appendix) was used to evaluate the
      experimental results. The model reproduces with great precision the
      characteristic features of the force-stiffness-velocity relationships recorded in
      intact muscle fibres.

PMID- 9288683
TI  - Fusimotor influence on jaw muscle spindle activity during swallowing-related
      movements in the cat.
AB  - 1. The activity patterns of muscle spindle afferents in jaw-closer muscles were
      studied during reflex swallowing movements in anaesthetized cats. Simultaneous
      records were made of the electromyogram (EMG) in masseter and anterior digastric
      muscles and of the unloaded jaw movements. The underlying patterns of fusimotor
      activity were deduced by comparing afferent discharges occurring during active
      swallowing with those occurring when exactly the same movements were imposed
      passively. The interpretation of spindle behaviour was greatly facilitated by
      characterizing the afferents according to the evidence for their contact with the
      various intrafusal muscle fibres, derived from testing with succinylcholine. It
      was also valuable to have two different types of afferent recorded
      simultaneously. 2. There was clear evidence of fusimotor activity occurring
      during active jaw closing so as to oppose the spindle silencing. This effect was
      most marked in b2c-type afferents (probably secondaries) and was therefore
      attributed to a modulation of static fusimotor discharge approximately in
      parallel with alpha-activity. 3. Afferents with evidence of bag1 fibre contacts
      (primaries) showed much greater sensitivity to muscle lengthening during active
      movement than when the movement was imposed. This difference was exaggerated when
      anaesthesia was deepened for the passive movements. This was interpreted as
      evidence for a higher level of dynamic fusimotor activity maintained during
      active movements than at rest. 4. The results support the view that for a variety
      of active jaw movements, static fusimotor neurone firing is modulated roughly in
      parallel with alpha-activity but leading it so as to counteract spindle
      unloading. Dynamic fusimotor neurone firing appears to be set at a raised level
      during active movements. Anaesthesia appears to depress activity in the alpha
      motoneurones more than in gamma-motoneurones.

PMID- 9288684
TI  - Increased sensitivity of gastrin cells to gastric distension following antral
      denervation in the rat.
AB  - 1. Secretion of the antral hormone gastrin is increased by protein in the gastric
      lumen and by nervous reflexes. We have examined the relative importance of
      luminal and neuronal mechanisms, by lesioning the antral innervation using
      benzalkonium chloride. 2. Benzalkonium chloride was applied to the serosa of the
      antrum in anaesthetized rats. In some animals, a stainless-steel cannula was also
      implanted in the corpus. Animals were allowed 10 days to recover. Plasma gastrin
      was measured by radioimmunoassay and mRNAs encoding gastrin, somatostatin and
      histidine decarboxylase were measured by Northern blot. 3. Antral denervation was
      associated with gastric retention after fasting, and elevated plasma gastrin
      (28.4 +/- 7 pM compared with 7.6 +/- 1.0 pM in controls). When fasted control or
      denervated rats were refed, plasma gastrin increased 3-fold in both cases. A
      gastrin-releasing peptide antagonist inhibited the post-prandial rise in plasma
      gastrin in control rats, but had no effect in antrally denervated rats. 4. In
      fasted, antrally denervated rats with a gastric fistula, basal gastric acid
      secretion was depressed 3-fold, and plasma gastrin concentrations were similar to
      controls. 5. Distension of the stomach with peptone via a barostat attached to
      the gastric cannula (5 cm H2O, 30 min), produced 3-fold increases in plasma
      gastrin in both control and denervated rats. However, distension with a non
      nutrient solution at pH 6.0 had no effect in controls, but increased gastrin to a
      similar extent to peptone in denervated rats; distension with 50 mM HCl had no
      effect in either control or denervated rats. 6. Somatostatin and gastrin mRNA
      abundances in the antrum were depressed by about 35% by antral denervation, but
      somatostatin mRNA in the corpus was unchanged; GAPDH mRNA abundance was
      unaffected by antral denervation. 7. The data suggest that luminal nutrient
      releases gastrin in the rat, in vivo, via activation of antral neurons secreting
      gastrin-releasing peptide, and that the antral innervation normally inhibits G
      cell responses to non-nutrient distension of the stomach. After antral
      denervation, gastric distension with a non-nutrient solution is an adequate
      stimulus for gastrin release.

PMID- 9288685
TI  - Effect of midbrain stimulations on thermoregulatory vasomotor responses in rats.
AB  - 1. Efferent projections eliciting vasodilatation when the preoptic area is warmed
      were investigated by monitoring tail vasomotor responses of ketamine
      anaesthetized rats when brain areas were stimulated electrically (0.2 mA, 200
      microseconds, 30 Hz) or with the excitatory amino acid D,L-homocysteic acid (1
      mM, 0.3 microliter). 2. Both stimulations elicited vasodilatation when applied
      within a region extending from the most caudal part of the lateral hypothalamus
      to the ventrolateral periaqueductal grey matter (PAG) and the reticular formation
      ventrolateral to the PAG. 3. Vasodilatation elicited by preoptic warming was
      suppressed when either stimulation was applied within the rostral part of the
      ventral tegmental area (VTA). 4. Sustained vasodilatation was elicited by knife
      cuts caudal to the VTA, and vasodilatation elicited by preoptic warming was
      suppressed by cuts either rostral to the VTA or in the region including the PAG
      and the reticular formation ventrolateral to it. 5. These results, together with
      the results of earlier physiological and histological studies, suggest that warm
      sensitive neurones in the preoptic area send excitatory signals to vasodilatative
      neurones in the caudal part of the lateral hypothalamus, ventrolateral PAG and
      reticular formation, and send inhibitory signals to vasoconstrictive neurones in
      the rostral part of the VTA.

PMID- 9288686
TI  - Development of carotid chemoreceptor dynamic and steady-state sensitivity to CO2
      in the newborn lamb.
AB  - 1. The maturation of carotid chemoreceptor steady-state and dynamic responses to
      CO2 in newborn lambs was measured. In total, sixteen fibres (13 lambs) were
      studied at 3-4 days, nineteen fibres (13 lambs) at 5-9 days and twenty-one fibres
      (17 lambs) at 10-24 days after birth. 2. Steady-state CO2 sensitivity was
      measured over a range of arterial CO2 pressures (Pa,CO2) at four levels of
      arterial O2 pressure (Pa,O2): hyperoxia (Hyp), 115-150 mmHg; normoxia (Nx), 90
      105 mmHg; moderate hypoxia (ModHx), 40-60 mmHg; and severe hypoxia (SvHx), 20-35
      mmHg. 3. Steady-state CO2 sensitivity was present at all ages, and a significant
      effect of age (P < 0.001) and Pa,O2 (P < 0.025) (ANOVA) was observed. Older lambs
      were unable to sustain an increase in chemoreceptor discharge during SvHx as CO2
      was increased. 4. Dynamic CO2 sensitivity was measured by producing alternations
      in end-tidal CO2 levels (etCO2) (alternation amplitude, 1.23 +/- 0.07% (mean +/-
      S.E.M.); etCO2, 7.56 +/- 0.15%) over 2-8 s at two Pa,O2 levels only: 80-100 (Nx)
      and 40-60 mmHg (ModHx). Peak and trough values of the oscillation in
      chemoreceptor discharge were plotted against maximum and minimum etCO2 for the
      control and CO2-loaded breaths. Dynamic CO2 sensitivity was calculated as the
      slope between these points. 5. Dynamic CO2 sensitivity was greater than steady
      state sensitivity in Nx (P < 0.05) and ModHx (P < 0.01, Student's paired t test).
      Unlike steady-state CO2 sensitivity, there was no significant effect of age or
      Pa,O2 on dynamic sensitivity (P > 0.39 and P > 0.68, respectively, ANOVA). 6. Our
      results show that the neonatal lamb possesses a carotid body steady-state CO2
      sensitivity within a few days of birth, an age when hypoxia sensitivity is low.
      This CO2 sensitivity increases with age, perhaps due to the increasing
      interaction between CO2 and O2. Dynamic sensitivity of the carotid body to CO2 is
      mature at birth and does not increase with age, as predicted if the response of
      the carotid body to rapid changes in CO2 is independent of the sensitivity to the
      partial pressure of O2 (PO2).

PMID- 9288687
TI  - Oxygen transport and utilization during feeding in the young lamb.
AB  - 1. Five lambs (19-27 days old) were studied to determine the effects of feeding
      on cardiorespiratory function. 2. Each lamb was instrumented to record cardiac
      output, aortic and pulmonary artery pressure and arterial and mixed venous
      oxyhaemoglobin saturations (Sa,O2 and Sv,O2). 3. During feeding, arterial
      haemoglobin desaturated and resaturated sequentially during the periods of
      sucking and non-sucking. The nadir of these Sa,O2 desaturations (83 +/- 2%, mean
      +/- S.E.M.) was significantly lower than the baseline value (92 +/- 2%, P < or =
      0.05, ANOVA). Sa,O2 returned to the baseline level between periods of sucking.
      Sv,O2 also decreased (55 +/- 3% baseline, 46 +/- 3% sucking, P < or = 0.05) but,
      in contrast to Sa,O2, it remained significantly lower than baseline levels in the
      pauses between periods of sucking. 4. Arterial pressure increased during feeding
      (94 +/- 4 mmHg baseline, 113 +/- 6 mmHg feeding, P < or = 0.05), while heart rate
      and cardiac index did not change. 5. Total body oxygen consumption rose during
      the pauses between sucking periods (10.9 +/- 1.1 ml O2 min-1 kg-1 baseline, 13.9
      +/- 1.2 ml O2 min-1 kg-1 non-sucking, P < or = 0.05) and was provided for by a
      significant increase in total body oxygen extraction as systemic oxygen transport
      was unchanged. 6. Our results reveal that during feeding in young lambs oxygen
      consumption increases and body stores of oxygen (e.g. Sv,O2) become depleted;
      this combination may promote rapid arterial desaturation and cyanosis during
      feeding.

PMID- 9288688
TI  - A comparison of the ventilatory response of sleeping newborn lambs to step and
      progressive hypoxaemia.
AB  - 1. Slight variations in the rate at which hypoxaemia develops may significantly
      alter the ventilatory response (VR) elicited. Here we have developed a technique
      to compare the VRs elicited from sleeping newborn lambs by specific (step versus
      progressive), short-duration (< or = 5 min) episodes of hypoxaemia. The results
      may help us understand the limitations of using tests which deliver poorly
      defined stimuli to evaluate the postnatal development of the oxygen chemoreflex.
      2. The VRs of five lambs elicited by a 5 min step or progressive reduction in the
      arterial oxygen saturation (Sa,O2) during quiet sleep were compared. Minute
      ventilation (V1, face mask) and Sa,O2 (pulse oximeter) were measured
      continuously. Alternate step (Sa,O2 reduced to 80-85% within 60 s and maintained
      for a further 4 min) and progressive tests (progressive reduction in Sa,O2 to 80%
      over 5 min) were administered daily between postnatal days 2-14. 3. There was a
      significant difference between the mean VR to step versus progressive hypoxaemia.
      The VR to a step challenge was biphasic (delta Vi = +32 +/- 5% at 1 min and -1 +/
      4% at 5 min; mean +/- S.E.M.). Progressive hypoxaemia elicited a more subdued
      but sustained hyperpnoea (delta Vi = +11 +/- 2% at 1 min and +11 +/- 4% at 5
      min). The difference between these two response profiles was statistically
      significant (P < 0.001). 4. Mean responses of lambs aged < or = 5 days (4 +/- 0.2
      days) and > or = 9 days (10 +/- 0.3 days) were also compared. There was an upward
      shift in the position of step and progressive response curves of older lambs,
      reflecting primarily the increased vigour of the initial hyperpnoea elicited by
      step (delta Vi at 1 min = +20 +/- 4% at 4 days vs. +40 +/- 11% at 10 days) as
      well as progressive (delta Vi at 1 min = +6 +/- 2% at 4 days vs. +17 +/- 5% at 10
      days) hypoxaemia. 5. Qualitatively different VRs may be elicited from the
      newborn, depending upon the specific hypoxaemic profile administered. Therefore,
      to evaluate the significance of VRs elicited in response to classical, steady
      state hypoxia at different postnatal ages properly, the stimulus must be
      accurately described.

PMID- 9288689
TI  - The effects of breathing He-O2 mixtures on maximal oxygen consumption in normoxic
      and hypoxic men.
AB  - 1. The hypothesis that the ventilatory resistance to O2 flow (RV) does limit
      maximal O2 consumption (VO2,max) in hypoxia, but not in normoxia, at least in non
      athletic subjects, was tested. RV was reduced by using He-O2 mixtures. 2. VO2,max
      was measured during graded cyclo-ergometric exercise in eight men (aged 30 +/- 3
      years) who breathed N2-O2 and He-O2 mixtures in normoxia (inspired oxygen
      fraction (FI,O2) = 0.21) and hypoxia (FI,O2 = 0.11). O2 consumption, expired and
      alveolar ventilations (VE and VA, respectively), blood lactate and haemoglobin
      concentrations, heart rate and arterial oxygen saturation (Sa,O2) were determined
      at the steady state of each work load. Arterial O2 and CO2 partial pressures
      (Pa,O2 and Pa,CO2, respectively) were measured at rest and at the end of the
      highest work load. 3. Maximal VE and VA were significantly increased by He-O2
      breathing in normoxia (+27 and +18%, respectively), without significant changes
      in Pa,O2, Sa,O2 and VO2,max. In hypoxia, VE and VA increased (+31 and +24%,
      respectively), together with Pa,O2 (+17%), Sa,O2 (+6%) and VO2,max (+14%). 4. The
      results support the hypothesis that the role of RV in limiting VO2,max is
      negligible in normoxia. In hypoxia, the finding that higher VE and VA values
      during He-O2 breathing led to higher VO2,max values suggests a greater role of RV
      as a limiting factor. It is unclear whether the finding that the VO2,max values
      were the same during He-O2 and N2-O2 breathing in normoxia is due to a non-linear
      response of the O2 transfer system, as previously proposed.

PMID- 9288691
TI  - Estrogen and heart disease: trials to prevent tribulations.

PMID- 9288690
TI  - Lymph flow pattern in the intact thoracic duct in sheep.
AB  - 1. To study the lymph flow dynamics in the intact thoracic duct, we applied an
      ultrasound transit-time flow probe in seven anaesthetized and four
      unanaesthetized adult sheep (approximately 60 kg). In unanaesthetized non-fasting
      animals we found that lymph flow in the thoracic duct was always regular
      pulsatile (pulsation frequency, 5.2 +/- 0.8 min-1) with no relation to heart or
      respiratory activity. At baseline the peak level of the thoracic duct pulse flow
      was 11.6-20.7 ml min-1 with a nadir of 0-3.6 ml min-1. Mean lymph flow was 5.4 +/
      3.1 ml min-1. The flow pattern of lymph in the thoracic duct was essentially the
      same in the anaesthetized animals. 2. In both the anaesthetized and
      unanaesthetized animals, the lymph flow response to a stepwise increase in the
      outflow venous pressure showed interindividual variation. Some were sensitive to
      any increase in outflow venous pressure, but others were resistant in that lymph
      flow did not decrease until outflow venous pressure was increased to higher
      levels. This resistance was also observed in the high lymph flow condition
      produced by fluid infusion in the anaesthetized animal and mechanical
      constriction of the caudal vena cava in the unaesthetized animals. Pulsation
      frequency of the thoracic duct flow initially increased and then decreased with a
      stepwise increase in the outflow venous pressure. This initial increase might be
      a compensatory response to maintain lymph flow against elevated outflow venous
      pressure. 3. To test the effect of long-term outflow venous pressure elevation in
      unanaesthetized sheep, outflow venous pressure was increased by inflation of a
      cuff around the cranial vena cava for 1, 5 or 25 h. The cuff was inflated to a
      level where lymph flow was reduced. Lymph flow remained low or decreased further
      during the entire cuff-inflation period. We calculated the lymph debt caused by
      the outflow venous pressure elevation and the amount 'repaid' when venous
      pressure returned to normal. Lymph debt for 25 h was 6400 ml but only 200 ml was
      repaid. Since we observed no visible oedema formation in the lower body of the
      sheep, the non-colloidal components of the lymph must have been reabsorbed into
      the bloodstream, most likely in the lymph nodes.

PMID- 9288692
TI  - Differential diagnosis of hot flashes.
AB  - OBJECTIVE: The purpose of this study is to present the physiology and
      differential diagnosis of hot flashes, other than associated with menopause, in
      order to facilitate the proper evaluation of symptomatic patients with hot
      flashes. STUDY DESIGN: Literature search using Med-Line computer access. RESULTS:
      Interest in flushing reaction began in historic times. With the rapidly expanding
      population of women over the age of 45 and prevalence of hot flashes as
      menopausal symptoms, physicians need to be aware of other medical conditions
      which may mimic hot flashes. These include flushing due to systemic diseases,
      carcinoid syndrome, systemic mast cell disease, pheochromocytoma, medullary
      carcinoma of the thyroid, pancreatic islet-cell tumors, renal cell carcinoma,
      neurological flushing, emotional flushing, spinal cord injury, flushing reaction
      related to alcohol and drugs, flushing associated with food additives and eating.
      CONCLUSION: There is a wide variety of disease processes that can cause hot
      flashes. Knowledge of the nature of these disease processes is necessary for
      quick recognition of patients with hot flashes who do not respond to estrogen
      replacement treatment, and to facilitate the proper evaluation of atypical
      patients.

PMID- 9288693
TI  - Perceived control over menopausal hot flushes: exploring the correlates of a
      standardised measure.
AB  - OBJECTIVES: A substantial minority of women report considerable distress during
      hot flushes. Coping with various chronic health problems has been related to
      perceived control in previous studies. Hence this study developed a standardised
      measure to investigate whether perceived control is associated with less distress
      during menopausal hot flushes. METHOD: The study presented a suitably re-worded
      15-item scale (the Arthritis Helplessness Index, originally developed by Nicassio
      et al., J Rheumatol 1985;12:462-467. Scoring was reversed so that high scores
      signified greater perceived control. A volunteer sample of 43 women (mean age 51
      years) completed the scale together with several further measures. A total of 35
      women returned 12 month follow-up questionnaires. RESULTS: The Perceived Control
      Index (PCI) scores correlated with standardised measures of self-esteem and
      simple self-ratings (0-100) of perceived control, and remained very stable over
      12 months. Self-rated distress during flush episodes was more closely related to
      perceived control than to more objective factors such as flush frequency and
      chronicity. CONCLUSION: These findings support further investigation into whether
      subjective coping with flushes may be improved by psychological interventions
      that enhance perceived control and self-esteem.

PMID- 9288694
TI  - Determinants of self rated menopause status.
AB  - This study, based on a population survey, examines the self ratings of progress
      through the menopausal transition of women in natural menopause, women using
      hormone therapy and women who have undergone hysterectomy. The latter two groups
      are usually excluded from discussions of menopausal transition, since the
      accepted menstrually defined criteria do not apply to them. Hysterectomised women
      do not differ in their self rating profile from non-hysterectomised women, after
      hormone therapy status is taken into account. This is surprising, since they may
      have been expected to see themselves as in the main postmenopausal. Use of
      hormone therapy is tantamount to self perception as at least perimenopausal.
      Among women in natural menopause there is 29% disagreement between self ratings
      and menstrually defined categories. On the basis of these observations it is
      hypothesised that experience of symptoms associated with menopause is important
      in determining self ratings. The good fit of logistic regression predictions of
      self ratings from hysterectomy status, hormone therapy status and experience of
      hot flushes is consistent with this hypothesis. This research indicates that it
      is important to take women's subjective evaluations into account in assessing
      progress through the menopausal transition.

PMID- 9288695
TI  - Impaired ovarian function and risk factors for atherosclerosis in premenopausal
      women.
AB  - OBJECTIVES: The aim of the study was to obtain information on the possible
      relationship between impaired ovarian function and risk factors for
      cardiovascular disease. MATERIAL AND METHODS: Serum lipid levels, plasma
      fibrinolytic potential and histological and biochemical changes in the intima of
      the uterine artery were investigated in premenopausal women with irregular
      menstrual cycles, and the results were compared with those from regularly
      menstruating women. In addition, the same parameters were studied in
      postmenopausal women on hormone replacement therapy (HRT) and in postmenopausal
      women who had never used HRT. In total 64 patients undergoing hysterectomy for
      benign reasons were included the study. RESULTS: Plasma fibrinogen concentration
      was significantly higher in irregularly menstruating women as compared with women
      with regular cycles. In women with irregular cycles thickened or sclerotic
      arterial intima was a significantly more common finding as compared with
      regularly menstruating women. A significant positive correlation was observed
      between plasma fibrinogen concentration and intimal esterified cholesterol
      content in women with thickened or sclerotic uterine artery. CONCLUSIONS: These
      data suggest an important role for normal ovarian function in the prevention of
      atherosclerosis.

PMID- 9288696
TI  - A study of European womens' experience of the problems of urogenital ageing and
      its management.
AB  - OBJECTIVES: A six country Pan-European study of aspects of urogenital ageing
      (UGA). METHODS: The study was carried out using a stratified random sample of
      3000 women between the ages of 55 and 75 years. RESULTS: A total of 30% suffered
      from UGA symptoms, of whom 60% made efforts to alleviate their UGA problems, most
      commonly using HRT. There were some international differences regarding womens'
      perceptions of HRT, sexual relationships, prevalence and treatment of UGA
      problems and their attitudes to them across the six European States. CONCLUSIONS:
      Despite some international differences there was a generally similar experience
      of UGA problems across the six European populations studied, with a minority of
      women suffering significantly, however the distress of that subgroup highlighted
      the need for health professionals to appreciate the impact of UGA on those
      affected and to understand that many of these older women may be reticent in
      seeking help.

PMID- 9288697
TI  - A surprisingly ameliorating effect of high doses of estradiol in primary
      osteomyelofibrosis: a case report.
AB  - OBJECTIVES: To report a case of a postmenopausal woman with primary (idiopathic)
      osteomyelofibrosis who showed a considerable improvement under the effect of high
      doses of estradiol given for the control of severe intractable menopausal
      symptoms. METHODS: This study was carried out by a case report. RESULTS:
      Astonishingly, under the effect of high doses of estradiol, both clinical and
      laboratory indices of the disease were not only kept stable but also showed a
      noticeable improvement. Hemoglobin increased from a value of 8.4 gm/dl in 1989 to
      10.7 gm/dl in 1996. Blood transfusion was no longer necessary, the patient had
      had no infections whatsoever and was only afraid of not being allowed to continue
      using these high estrogen doses, which seemed indispensable and central to her
      well-being. CONCLUSIONS: High doses of estrogens could possibly be given the
      credit for ameliorating the natural sinister course of primary
      osteomyelofibrosis.

PMID- 9288698
TI  - The relationship of bacterial vaginosis, Candida and Trichomonas infection to
      symptomatic vaginitis in postmenopausal women attending a vaginitis clinic.
AB  - OBJECTIVE: To estimate the prevalence of bacterial vaginosis, Candida albicans,
      and Trichomonas vaginalis infections in a population of postmenopausal women with
      symptoms of vaginitis seen at a vaginitis clinic either as self-referred or
      clinician referred patients. METHODS: A cross-sectional study of 148
      postmenopausal women (cases) and 1564 controls of reproductive age attending a
      vaginitis clinic. C. albicans and T. vaginalis infections were diagnosed by
      culture techniques. Bacterial vaginosis was diagnosed on the basis of clinical
      findings. RESULTS: Fifty-six (37.8%) postmenopausal women and 834 (53.3%)
      controls were diagnosed with T. vaginalis or C. albicans infection, or bacterial
      vaginosis, or mixed infection (odds ratio (OR) 0.53, 95% confidence interval (CI)
      0.37-0.75). C. albicans and T. vaginalis infection were diagnosed in 34.1%
      (534/1564) and 1.92% (30/1564) of women of childbearing age and in 13.5% (20/148)
      and 10.8% of postmenopausal women, respectively. (P < 0.05 for both comparisons).
      The prevalence of bacterial vaginosis was similar between the two groups (14/148
      in postmenopausal patients and 210/1564 in controls of reproductive age; P =
      0.22). CONCLUSIONS: Among postmenopausal women attending a vaginitis clinic, a
      defined diagnosis of bacterial vaginosis, C. albicans or T. vaginalis infection
      can be made in about one third of such patients. Concerning the two thirds of
      symptomatic women lacking such a microbiologic diagnosis, alternative causes
      (e.g., estrogen deficiency, nonanaerobic bacterial infections, local irritants or
      allergenes, and dermatologic conditions) need to be considered.

PMID- 9288699
TI  - The Postmenopausal Estrogen/Progestin Interventions Study: primary outcomes in
      adherent women.
AB  - OBJECTIVE: To assess the efficacy of unopposed estrogen, and three
      estrogen/progestin regimens on selected heart disease risk factors among adherent
      women and to contrast those results with efficacy among all women in the PEPI
      study. DESIGN: A 3-year, multicenter, randomized, double-blinded, placebo
      controlled clinical trial. PARTICIPANTS: A total of 847 healthy postmenopausal
      women aged 45 to 64 years of age with no known contraindication to hormone
      therapy, who attended their 36 month clinical visit. INTERVENTION: Participants
      were randomized in equal numbers to one of the following treatments: (1) placebo;
      (2) conjugated equine estrogen (CEE) 0.625 mg daily; (3) CEE 0.625 daily plus
      medroxyprogesterone acetate (MPA) 10 mg, days 1-12; (4) CEE 0.625 daily plus MPA
      2.5 mg daily; or (5) CEE 0.625 daily plus micronized progesterone (MP) 200 mg,
      days 1-12. ANALYSIS: Analyses are based on adherent women, where adherence is
      defined as taking at least 80% of pills at each 6-month visit. RESULTS: Adherence
      rates were high in all groups except women with a uterus assigned to unopposed
      CEE. The difference in HDL-C levels resulting from the CEE vs. CEE+MP was
      approximately three times larger than in the intent-to-treat analyses, reaching
      statistical significance (P < 0.05). In each active treatment, LDL-C decreased 10
      15%. Triglycerides increased 15-20% in each opposed CEE arm and over 25% in the
      CEE only arm; this difference was not statistically significant. Fibrinogen
      increased by 7% among placebo adherers, but decreased or remained fairly stable
      among the active arm adherers. Systolic blood pressure increased 3-5% in all
      treatment arms. Women adherent to the CEE+MPA arms had twice the increase of 2 h
      glucose levels as women adherent to CEE only, or CEE+MP (8-9% vs. 3-4%). Two-hour
      insulin levels decreased 3-12% for all arms. The patterns of change for
      fibrinogen, SBP, 2 h glucose and insulin were similar to those from the intent-to
      treat analyses. CONCLUSIONS: In analyses limited to adherent women, all active
      treatments, compared to placebo, continued to have similar and favorable effects
      on LDL-cholesterol and fibrinogen and no significant effects on blood pressure or
      insulin levels. Given the overall high adherence rates in PEPI, the results are
      similar to the intent-to-treat analyses, as expected. Only the trend of HDL-C to
      have a larger increase in the CEE only arm (in the intent-to-treat analyses)
      gained statistical significance in analyses restricted to adherers.

PMID- 9288700
TI  - Metabolic effect of two hormonal preparations in postmenopausal women.
AB  - OBJECTIVES: To compare the metabolic and endocrinological effects of estradiol
      valerate/cyproterone acetate (EV/CPA) to a regimen of conjugated
      estrogens/medroxyprogesterone acetate (CE/MPA) in postmenopausal women. METHODS:
      Lipid profile, endocrinological parameters, coagulation factors, renin and
      angiotensinogen were followed in postmenopausal women randomized to EV/CPA or
      CE/MPA during 12 cycles. RESULTS: Following 12 cycles of treatment, total plasma
      cholesterol decreased more with EV/CPA than with CE/MPA. Low-density cholesterol
      decreased with EV/CPA while it increased with CE/MPA. High-density cholesterol
      remained fairly unchanged, and triglycerides increased significantly in both
      groups. Estradiol and estrone levels increased significantly more with EV/CPA
      than with CE/MPA while the sex-hormone-binding globulin increased more with
      CE/MPA. Follicle stimulating and luteinizing hormone levels also decreased
      significantly. Total testosterone and dihydroepiandrosterone sulfate remained
      stable. Total levothyroxine serum levels increased significantly, but thyroid
      stimulating hormone and triiodothyronine levels remained stable. Coagulation
      parameters also remained stable. Angiotensinogen increased, while plasma renin
      activity and blood pressure remained unchanged. CONCLUSION: It is concluded that
      both EV/CPA and CE/MPA produce favourable metabolic effects. A better lipid
      profile, compatible with decreased cardiovascular risk, is observed with the
      EV/CPA regimen. Higher circulating estrogen levels may explain in part this
      observation.

PMID- 9288701
TI  - Efficacy and tolerability of Estraderm MX, a new estradiol matrix patch.
AB  - OBJECTIVES: To assess the efficacy and tolerability of a new matrix patch
      delivering 0.05 mg estradiol per day (Estraderm MX 50) in postmenopausal women
      with moderate to severe postmenopausal symptoms. METHODS: A multicenter, double
      blind, randomized, between-patient, placebo controlled trial in 109
      postmenopausal women was carried out. Patches were applied twice weekly for 12
      weeks. Patients were assessed at 4, 8 and 12 weeks of treatment. The primary
      efficacy variable was change from baseline in mean number of moderate to severe
      hot flushes (including night sweats) per 24 h during the last 2 weeks of
      treatment. Other variables included Kupperman Index, local and systemic
      tolerability. Plasma concentrations of estradiol (E2), estrone (E1) and estrone
      sulfate (E1S) were determined before and after treatment. RESULTS: Estraderm MX
      was significantly superior to placebo (P < 0.001) in reducing mean number of
      moderate to severe hot flushes (including night sweats) per 24 h after 4, 8 and
      12 weeks of treatment. The estimate of treatment group differences after 12 weeks
      was 4.2 hot flushes (95% confidence interval: 2.6-5.8). Estraderm MX also
      significantly reduced Kupperman Index at all time points compared to placebo (P <
      0.001). Estraderm MX induced increases in mean E2, E1 and E1S plasma levels as
      expected (E2: baseline 2.7 pg/ml, 12 weeks 38.9 pg/ml; E1: baseline 18.8 pg/ml,
      12 weeks 41.6 pg/ml; E1S: baseline 235.6 pg/ml, 12 weeks 765.1 pg/ml). Overall
      rates of adverse experiences were similar for Estraderm MX and placebo. The
      number of patients reporting skin irritation was low and similar in both groups.
      CONCLUSIONS: Estraderm MX 50, a new matrix patch, offers an effective and well
      tolerated dosage form for transdermal delivery of 0.05 mg E2 per day.

PMID- 9288702
TI  - Guidance on xenotransplantation sought.

PMID- 9288703
TI  - Mathematical models of HIV pathogenesis.

PMID- 9288706
TI  - Tobacco money to pay for diabetes research.

PMID- 9288704
TI  - Is leptin a stress related peptide?

PMID- 9288705
TI  - IL-16 anti-HIV-1 therapy.

PMID- 9288707
TI  - Coming closer to FDA reform.

PMID- 9288708
TI  - Who will pay for Britain's university teaching and research?

PMID- 9288709
TI  - Vaccines beyond 2000.

PMID- 9288710
TI  - AIDS patients demand drugs as government hesitates.

PMID- 9288711
TI  - Modification of vascular responses in xenotransplantation: inflammation and
      apoptosis.

PMID- 9288712
TI  - The Howard Hughes Medical Institute and science in Central Europe, the Baltics
      and the former Soviet Union.

PMID- 9288713
TI  - Xenografts, cloning and the immune system.

PMID- 9288714
TI  - The reproductive side of leptin.

PMID- 9288715
TI  - Caspases: a treatment target for neurodegenerative disease?

PMID- 9288716
TI  - Plumbing the depths of dental decay.

PMID- 9288717
TI  - Epilepsy and the too-well-connected brain.

PMID- 9288718
TI  - A brighter future for cataract surgery.

PMID- 9288719
TI  - Gotta find GATA a friend.

PMID- 9288720
TI  - Which guesstimate is the best guesstimate? Predicting chemotherapeutic outcomes.

PMID- 9288721
TI  - Benefits and risks of hosting animal cells in the human brain.

PMID- 9288723
TI  - Adrenocortical tissue formed by transplantation of normal clones of bovine
      adrenocortical cells in scid mice replaces the essential functions of the
      animals' adrenal glands.
AB  - Xenotransplanted adrenocortical tissue of clonal origin was formed in
      immunodeficient (scid) mice by using techniques of cell transplantation. The
      experiments reported here used a single clone of bovine adrenocortical cells, but
      5 of 20 other randomly selected clones also formed tissue. Most adrenalectomized
      animals bearing transplanted cells survived indefinitely, demonstrating that the
      cells restored the animals' capacity to survive in the absence of sodium
      supplementation. Formation of well-vascularized tissue at the site of
      transplantation was associated with stable levels of cortisol in the blood,
      replacing the mouse glucocorticoid (corticosterone). Ultrastructurally, the
      cultured cells before transplantation had characteristics of rapidly growing
      cells, but tissue formed in vivo showed features associated with active
      steroidogenesis. These experiments show that an endocrine tissue can be derived
      from a single, normal somatic cell.

PMID- 9288722
TI  - The fate of individual myoblasts after transplantation into muscles of DMD
      patients.
AB  - Muscle biopsies from six patients with Duchenne muscular dystrophy (DMD)
      participating in a myoblast transplantation clinical trial were reexamined using
      a fluorescence in situ hybridization (FISH)-based method. Donor nuclei were
      detected in all biopsies analyzed, including nine where no donor myoblasts were
      previously thought to be present. In three patients, more than 10% of the
      original number of donor cells were calculated as present 6 months after
      implantation. Half of the detected donor nuclei were fused into host myofibers,
      and of these, nearly 50% produced dystrophin. These findings demonstrate that
      although donor myoblasts have persisted after injection, their microenvironment
      influences whether they fuse and express dystrophin. Our methodology could be
      used for developing new approaches to improve myoblast transfer efficacy and for
      the analysis of future gene- and/or cell-based therapies of numerous genetic
      disorders.

PMID- 9288724
TI  - Acquired CD40-ligand deficiency in chronic lymphocytic leukemia.
AB  - Patients with B-cell chronic lymphocytic leukemia (CLL) acquire an
      immunodeficiency with many characteristics similar to those of persons with
      inherited defects in the gene encoding the CD40-ligand (CD154). We found that the
      blood and splenic CD4+ T cells of patients with CLL failed to express surface
      CD154 after CD3 ligation. However, using an enzyme-linked immunosorbent assay
      (ELISA)-based quantitative competitive polymerase chain reaction (PCR), we noted
      that CD3 ligation could induce such T cells to express CD154 messenger RNA at
      levels similar to that of CD3-activated T cells from normal donors. Moreover,
      addition of increasing numbers of CLL B cells to activated normal donor T cells
      rapidly resulted in progressively greater down-modulation of CD154. Such down
      modulation of CD154 could be blocked by addition of CD40 monoclonal antibody to
      cultures in vitro. We propose that leukemia cell-mediated down-modulation of
      CD154 on activated T cells accounts for some of the acquired immune defects of
      patients with CLL.

PMID- 9288725
TI  - Lesion-induced axonal sprouting and hyperexcitability in the hippocampus in
      vitro: implications for the genesis of posttraumatic epilepsy.
AB  - The delayed development of recurring seizures is a common consequence of
      traumatic head injury; the cause of such epilepsy is unknown. We demonstrate here
      that transection of the mature axons of CA3 pyramidal cells in hippocampal slice
      cultures leads to the formation by CA3 pyramidal cells of new axon collaterals
      that are immunoreactive with the growth-associated protein GAP-43. Individual CA3
      cell axons had an elevated number of presynaptic boutons 14 days after the
      lesion, and dual intracellular recordings revealed an increased probability that
      any two CA3 pyramidal cells were connected by an excitatory synapse. Lesioned
      cultures were hyperexcitable and synaptic responses often displayed unusual
      prolonged polysynaptic components. We thus demonstrate that recurrent axon
      collaterals are newly sprouted by pyramidal cells as a consequence of axonal
      injury and suggest that this underlies the development of posttraumatic epilepsy.

PMID- 9288726
TI  - Elevation of neuronal expression of NAIP reduces ischemic damage in the rat
      hippocampus.
AB  - We show here that transient forebrain ischemia selectively elevates levels of
      neuronal apoptosis inhibitory protein (NAIP) in rat neurons that are resistant to
      the injurious effects of this treatment. This observation suggests that
      increasing NAIP levels may confer protection against ischemic cell death.
      Consistent with this proposal, we demonstrate that two other treatments that
      increase neuronal NAIP levels, systemic administration of the bacterial alkaloid
      K252a and intracerebral injection of an adenovirus vector capable of
      overexpressing NAIP in vivo, reduce ischemic damage in the rat hippocampus. Taken
      together, these findings suggest that NAIP may play a key role in conferring
      resistance to ischemic damage and that treatments that elevate neuronal levels of
      this antiapoptotic protein may have utility in the treatment of stroke.

PMID- 9288727
TI  - Progesterone inhibits arterial smooth muscle cell proliferation.
AB  - Mortality from atherosclerotic cardiovascular disease is lower in premenopausal
      women than in age-matched men. It is also lower in postmenopausal women who take
      estrogens and progestins together rather than estrogens alone. Progesterone
      receptors were detected in human and rat aortic smooth muscle cells in vivo and
      in vitro (in subculture). We examined the effect of progesterone on proliferation
      of smooth muscle cells, important constituents of atherosclerotic plaques.
      Progesterone at physiologic levels inhibited DNA synthesis and proliferation in
      these cells in a dose-dependent manner, and pretreatment with the progesterone
      receptor antagonist RU486 blocked inhibition. Cyclin A and E messenger RNA levels
      decreased after progesterone treatment but those of cyclin B and D1 did not
      change. This cell cycle-dependent inhibition of arterial smooth muscle cell
      proliferation by progesterone may represent a mechanism for the hormone's
      protective effect against atherosclerosis.

PMID- 9288728
TI  - Allelic origin of the abnormal prion protein isoform in familial prion diseases.
AB  - The hallmark of prion diseases is the presence of an aberrant isoform of the
      prion protein (PrP(res)) that is insoluble in nondenaturing detergents and
      resistant to proteases. We investigated the allelic origin of PrP(res) in brains
      of subjects heterozygous for the D178N mutation linked to fatal familial insomnia
      (FFI) and a subtype of Creutzfeldt-Jakob disease (CJD178), as well as for
      insertional mutations associated with another CJD subtype. We found that in FFI
      and CJD178 subjects, only mutant PrP was detergent-insoluble and protease
      resistant. Therefore, PrP(res) derives exclusively from the mutant allele
      carrying the D178N mutation. In contrast, in the CJD subtype harboring
      insertional mutations, wild-type PrP was also detergent-insoluble and likely to
      be protease-resistant. Our findings indicate that the participation of the wild
      type PrP in the formation of PrP(res) depends on the type of mutations, providing
      an insight into the molecular mechanisms underlying the phenotypic heterogeneity
      in familial prion diseases.

PMID- 9288729
TI  - Distinct sites of intracellular production for Alzheimer's disease A beta40/42
      amyloid peptides.
AB  - The Alzheimer amyloid precursor protein (APP) is cleaved by several proteases,
      the most studied, but still unidentified ones, are those involved in the release
      of a fragment of APP, the amyloidogenic beta-protein A beta. Proteolysis by gamma
      secretase is the last processing step resulting in release of A beta. Cleavage
      occurs after residue 40 of A beta [A beta(1-40)], occasionally after residue 42
      [A beta(1-42)]. Even slightly increased amounts of this A beta(1-42) might be
      sufficient to cause Alzheimer's disease (AD) (reviewed in ref. 1, 2). It is thus
      generally believed that inhibition of this enzyme could aid in prevention of AD.
      Unexpectedly we have identified in neurons the endoplasmic reticulum (ER) as the
      site for generation of A beta(1-42) and the trans-Golgi network (TGN) as the site
      for A beta(1-40) generation. It is interesting that intracellular generation of A
      beta seemed to be unique to neurons, because we found that nonneuronal cells
      produced significant amounts of A beta(1-40) and A beta(1-42) only at the cell
      surface. The specific production of the critical A beta isoform in the ER of
      neurons links this compartment with the generation of A beta and explains why
      primarily ER localized (mutant) proteins such as the presenilins could induce AD.
      We suggest that the earliest event taking place in AD might be the generation of
      A beta(1-42) in the ER.

PMID- 9288730
TI  - Alzheimer's A beta(1-42) is generated in the endoplasmic reticulum/intermediate
      compartment of NT2N cells.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder involving the florid
      deposition of vascular and cerebral plaques composed chiefly of amyloid beta
      peptide (A beta) derived from cleavage of the amyloid precursor protein (APP).
      Varying in length from 39 to 43 amino acids, A beta, particularly the longer A
      beta(42), is thought to play a significant role in AD pathogenesis. To better
      understand AD it is important to identify the subcellular organelles generating A
      beta. Studies using agents that disrupt endosomal/lysosomal function suggest that
      A beta is generated late in the secretory and endocytic pathways. However, much
      of what is known about A beta biosynthesis has been inferred by monitoring
      extracellular A beta levels since intracellular A beta is undetectable in most
      cell types. Consequently, the precise site or sites that generate A beta, or
      whether A beta(1-40) and A beta(1-42) are generated at the same point in the
      biosynthetic pathway, is not known. Using human NT2N neurons, we found that
      retention of APP in the endoplasmic reticulum/intermediate compartment (ER/IC) by
      three independent approaches eliminated production of intracellular A beta(1-40),
      but did not alter intracellular A beta(1-42) synthesis. These findings suggest
      that the ER/IC may be an important site for generating this highly amyloidogenic
      species of A beta.

PMID- 9288731
TI  - Influence of maternal lead ingestion on caries in rat pups.
AB  - Lead is one of the most toxic and pervasive pollutants in society, and although
      there has been some lowering of blood lead levels in recent years, the levels
      continue to be of concern for African Americans, central city residents,
      residents in the Northeast region of the United States, persons with low income,
      and those with low educational attainment. Notably, these are the persons and the
      region where the highest prevalence of dental caries is observed. Information
      relating lead toxicity to oral health is sparse, but the preponderance of
      epidemiological data shows a relation between lead in the environment and the
      prevalence of dental caries. Using our well-defined rat caries model we found
      that pre- and perinatal exposure to lead results in an almost 40% increase in the
      prevalence of caries and a decrease in stimulated parotid function of nearly 30%.
      Levels of lead in milk from lead-treated dams were approximately 10 times as high
      as the corresponding blood lead levels, suggesting that lead is being
      concentrated by mammary glands. These findings may help in part to explain the
      comparatively high levels of dental caries observed in the inner cities of the
      United States where exposure to lead is common. Environmental sources of lead
      include drinking water, lead-based paint and, to a lesser extent, automobile and
      industrial emissions. In humans lead is accumulated and stored in bones (half
      life of approximately 62 years), and even maternal exposure to lead decades
      before pregnancy can subsequently result in exposure of the developing fetus to
      elevated levels of lead. Moreover, lead concentration in maternal blood has been
      shown to increase during pregnancy and lactation because of mobilization of
      stored lead from bone, and typically, lead is found in milk at a higher
      concentration than the level found in maternal plasma at the same time point.

PMID- 9288732
TI  - Thapsigargin-coated intraocular lenses inhibit human lens cell growth.
AB  - Cataract is responsible for rendering several million people blind throughout the
      world and is also by far the most common cause of low visual acuity. Although
      cataract surgery is common, routine and effective, posterior capsule
      opacification (PCO) occurs in 30-50% of patients following modern cataract
      surgery. This condition arises from stimulated cell growth within the capsular
      bag after surgery. The resulting decline in visual acuity requires expensive
      laser treatment, and PCO therefore prevents modern cataract surgery from being
      carried out routinely in underdeveloped countries. The present study, using a
      human lens capsular bag culture system, has confirmed that cells from a wide age
      range of donors proliferate in the absence of added serum protein and explains
      why PCO is such a common problem even in aged patients. This study also provides
      one possible solution for PCO by using polymethylmethacrylate (PMMA) implanted
      intraocular lenses as a drug delivery system. PMMA lenses coated with
      thapsigargin, a hydrophobic inhibitor of endoplasmic reticulum (ER) (Ca2+)
      ATPase, greatly reduced cell growth in the capsular bag at relatively low coating
      concentrations (200 nM) but, more significantly, induced total cell death of the
      residual anterior epithelial cells at higher concentrations (>2 microM).

PMID- 9288733
TI  - Nonadipose tissue production of leptin: leptin as a novel placenta-derived
      hormone in humans.
AB  - Leptin is a circulating hormone that is expressed abundantly and specifically in
      the adipose tissue. It is involved in the regulation of energy homeostasis, as
      well as the neuroendocrine and reproductive systems. Here, we demonstrate
      production of leptin by nonadipose tissue, namely, placental trophoblasts and
      amnion cells from uteri of pregnant women. We show that pregnant women secrete a
      considerable amount of leptin from the placenta into the maternal circulation as
      compared with nonpregnant obese women. Leptin production was also detected in a
      cultured human choriocarcinoma cell line, BeWo cells, and was augmented during
      the course of forskolin-induced differentiation of cytotrophoblasts into
      syncytiotrophoblasts. Plasma leptin levels were markedly elevated in patients
      with hydatidiform mole or choriocarcinoma and were reduced after surgical
      treatment or chemotherapy. Leptin is also produced by primary cultured human
      amnion cells and is secreted into the amniotic fluid. The present study provides
      evidence for leptin as a novel placenta-derived hormone in humans and suggests
      the physiologic and pathophysiologic significance of leptin in normal pregnancy
      and gestational trophoblastic neoplasms.

PMID- 9288734
TI  - Cell-cycle arrest versus cell death in cancer therapy.
AB  - In response to anticancer therapeutics, human colon cancer cells growing in vitro
      either enter into a stable arrest or die, depending on the integrity of their
      cell-cycle checkpoints. To test whether altered checkpoints can modulate
      sensitivity to treatment in vivo, xenografts were established from isogenic lines
      differing only in their p21 checkpoint status. Although all tumors with intact
      checkpoint function underwent regrowth after treatment with gamma-radiation, a
      significant fraction of checkpoint-deficient tumors were completely cured. This
      difference in sensitivity was not detected by the clonogenic survival assay,
      because both arrest and death preclude outgrowth of colonies. These results
      demonstrate that checkpoint status affects sensitivity to anticancer treatments
      in vivo, and these findings have important implications for identifying and
      testing new therapeutic compounds.

PMID- 9288736
TI  - Rapid construction of genome maps.

PMID- 9288735
TI  - Primary demyelination in transgenic mice expressing interferon-gamma.
AB  - Ever since the use of interferon-gamma to treat patients with multiple sclerosis
      resulted in enhanced disease, the role of IFN-gamma in demyelination has been
      under question. To address this issue directly, transgenic mice were generated
      that expressed the cDNA of murine IFN-gamma in the central nervous system by
      using an oligodendrocyte-specific promoter. Expression of the transgene occurred
      after 8 weeks of age, at which time the murine immune and central nervous systems
      are both fully developed. Directly associated with transgene expression, primary
      demyelination occurred and was accompanied by clinical abnormalities consistent
      with CNS disorders. Additionally, multiple hallmarks of immune-mediated CNS
      disease were observed including upregulation of MHC molecules, gliosis and
      lymphocytic infiltration. These results demonstrate a direct role for IFN-gamma
      as an inducer of CNS demyelination leading to disease and provide new
      opportunities for dissecting the mechanism of demyelination.

PMID- 9288737
TI  - Gut reaction to Wnt signaling in worms.

PMID- 9288738
TI  - Olfactory receptors, vomeronasal receptors, and the organization of olfactory
      information.

PMID- 9288739
TI  - Metalloprotease-disintegrins: links to cell adhesion and cleavage of TNF alpha
      and Notch.

PMID- 9288740
TI  - Activation of p53 sequence-specific DNA binding by acetylation of the p53 C
      terminal domain.
AB  - The tumor suppressor p53 exerts antiproliferation effects through its ability to
      function as a sequence-specific DNA-binding transcription factor. Here, we
      demonstrate that p53 can be modified by acetylation both in vivo and in vitro.
      Remarkably, the site of p53 that is acetylated by its coactivator, p300, resides
      in a C-terminal domain known to be critical for the regulation of p53 DNA
      binding. Furthermore, the acetylation of p53 can dramatically stimulate its
      sequence-specific DNA-binding activity, possibly as a result of an acetylation
      induced conformational change. These observations clearly indicate a novel
      pathway for p53 activation and, importantly, provide an example of an acetylation
      mediated change in the function of a nonhistone regulatory protein. These results
      have significant implications regarding the molecular mechanisms of various
      acetyltransferase-containing transcriptional coactivators whose primary targets
      have been presumed to be histones.

PMID- 9288741
TI  - Yeast TAF(II)145 required for transcription of G1/S cyclin genes and regulated by
      the cellular growth state.
AB  - TFIID comprises the TATA box-binding protein and a set of highly conserved
      associated factors (TAF(II)s). yTAF(II)145, the core subunit of the yeast TAF(II)
      complex, is dispensable for transcription of most yeast genes but specifically
      required for progression through G1/S. Here we show that transcription of G1 and
      certain B-type cyclin genes is dependent upon yTAF(II)145. At high cell density
      or following nutrient deprivation, yeast cells cease division, enter a G0-like
      state, and terminate transcription of most genes. In this stationary phase, we
      find that the levels of yTAF(II)145, several other yTAF(II)s, and TBP are
      drastically reduced. Collectively, our results indicate that yTAF(II)145 and
      other TFIID components have a specialized role in transcriptional regulation of
      cell cycle progression and growth control.

PMID- 9288742
TI  - Yeast TAF(II)145 functions as a core promoter selectivity factor, not a general
      coactivator.
AB  - In yeast, TATA box binding protein associated factors (TAF(II)s) are dispensable
      for transcription of most genes. Here we use differential display to identify a
      small subset of yeast genes whose transcription in vivo requires yTAF(II)145.
      Promoter-mapping studies reveal, unexpectedly, that the region of a gene that
      renders it yTAF(II)145-dependent is not the upstream activating sequence, which
      contains the activator-binding sites, but rather the core promoter. In fact, a
      core promoter requiring yTAF(II)145 retained that requirement when its
      transcription was directed by several unrelated upstream activating sequences and
      even in the absence of an activator. Taken together, our results indicate that
      yTAF(II)145 functions in recognition and selection of core promoters by a
      mechanism not involving upstream activators.

PMID- 9288743
TI  - ATP-dependent positive supercoiling of DNA by 13S condensin: a biochemical
      implication for chromosome condensation.
AB  - 13S condensin is a five-subunit protein complex that plays a central role in
      mitotic chromosome condensation in Xenopus egg extracts. Two core subunits of
      this complex, XCAP-C and XCAP-E, belong to an emerging family of putative
      ATPases, the SMC family. We report here that 13S condensin has a DNA-stimulated
      ATPase activity and exhibits a high affinity for structured DNAs such as
      cruciform DNA. 13S condensin is able to introduce positive supercoils into a
      closed circular DNA in the presence of bacterial or eukaryotic topoisomerase I.
      The supercoiling reaction is ATP-dependent. We propose that 13S condensin wraps
      DNA in a right-handed direction by utilizing the energy of ATP hydrolysis. This
      reaction may represent a key mechanism underlying the compaction of chromatin
      fibers during mitosis.

PMID- 9288744
TI  - Major domain swiveling revealed by the crystal structures of complexes of E. coli
      Rep helicase bound to single-stranded DNA and ADP.
AB  - Crystal structures of binary and ternary complexes of the E. coli Rep helicase
      bound to single-stranded (ss) DNA or ssDNA and ADP were determined to a
      resolution of 3.0 A and 3.2 A, respectively. The asymmetric unit in the crystals
      contains two Rep monomers differing from each other by a large reorientation of
      one of the domains, corresponding to a swiveling of 130 degrees about a hinge
      region. Such domain movements are sufficiently large to suggest that these may be
      coupled to translocation of the Rep dimer along DNA. The ssDNA binding site
      involves the helicase motifs Ia, III, and V, whereas the ADP binding site
      involves helicase motifs I and IV. Residues in motifs II and VI may function to
      transduce the allosteric effects of nucleotides on DNA binding. These structures
      represent the first view of a DNA helicase bound to DNA.

PMID- 9288745
TI  - Loading of an Mcm protein onto DNA replication origins is regulated by Cdc6p and
      CDKs.
AB  - In eukaryotic cells, firing of DNA replication origins normally does not recur
      until after M phase. This characteristic is thought to be due to the properties
      of "initiation" proteins like Orc, Cdc6, and Mcms. Using formaldehyde cross
      linking, we show that Cdc6p and Mcm7p associate specifically with replication
      origins during G1 but not during G2 in S. cerevisiae. Mcm7p's association with
      origins depends on Cdc6p. Ectopic expression of Cdc6p enables it to associate
      with origins during G2, but this fails to recruit Mcm7p. Our data suggest that
      the loading of Mcm proteins onto origins is regulated by two mechanisms: first,
      by Cdc6p occupancy, and second, by S- and M-CDKs, whose activity during S, G2,
      and M phases prevents Mcm loading.

PMID- 9288746
TI  - The crystal structure of plasma gelsolin: implications for actin severing,
      capping, and nucleation.
AB  - The structure of gelsolin has been determined by crystallography and comprises
      six structurally related domains that, in a Ca2+-free environment, pack together
      to form a compact globular structure in which the putative actin-binding
      sequences are not sufficiently exposed to enable binding to occur. We propose
      that binding Ca2+ can release the connections that join the N- and C-terminal
      halves of gelsolin, enabling each half to bind actin relatively independently.
      Domain shifts are proposed in response to Ca2+ as bases for models of how
      gelsolin acts to sever, cap, or nucleate F-actin filaments. The structure also
      invites discussion of polyphosphoinositide binding to segment 2 and suggests how
      mutation at Asp-187 could initiate a series of events that lead to deposition of
      amyloid plaques, as observed in victims of familial amyloidosis (Finnish type).

PMID- 9288747
TI  - Drosophila fizzy-related down-regulates mitotic cyclins and is required for cell
      proliferation arrest and entry into endocycles.
AB  - We demonstrate that fizzy-related (fzr), a conserved eukaryotic gene, negatively
      regulates the levels of cyclins A, B, and B3. These mitotic cyclins that bind and
      activate cdk1(cdc2) are rapidly degraded during exit from M and during G1. While
      Drosophila fizzy has previously been shown to be required for cyclin destruction
      during M phase, fzr is required for cyclin removal during G1 when the embryonic
      epidermal cell proliferation stops and during G2 preceding salivary gland
      endoreduplication. Loss of fzr causes progression through an extra division cycle
      in the epidermis and inhibition of endoreduplication in the salivary gland, in
      addition to failure of cyclin removal. Conversely, premature fzr overexpression
      down-regulates mitotic cyclins, inhibits mitosis, and transforms mitotic cycles
      into endoreduplication cycles.

PMID- 9288748
TI  - Yeast Hct1 is a regulator of Clb2 cyclin proteolysis.
AB  - Stage-specific proteolysis of mitotic cyclins is fundamental to eukaryotic cell
      cycle regulation. We found that yeast Hct1, a conserved protein of eukaryotes, is
      a necessary and rate-limiting component of this proteolysis pathway. In hct1
      mutants, the mitotic cyclin Clb2 is highly stabilized and inappropriately induces
      DNA replication, while G1 cyclins and other proteolytic substrates remain short
      lived. Viability of hct1 mutants depends on SIC1. This and further results
      suggest that inhibition of cyclin-dependent kinases may compensate for defects in
      cyclin proteolysis. Remarkably, elevated levels of Hct1 ectopically activate
      destruction box- and Cdc23-dependent degradation of Clb2 and cause phenotypic
      effects characteristic for a depletion of M-phase cyclins. Hct1 and the related
      Cdc20 may function as substrate-specific regulators of proteolysis during
      mitosis.

PMID- 9288749
TI  - Wnt signaling polarizes an early C. elegans blastomere to distinguish endoderm
      from mesoderm.
AB  - A polarizing signal induces endoderm production by a 4-cell stage blastomere in
      C. elegans called EMS. We identified 16 mutations in five genes, mom-1 through
      mom-5, required for EMS to produce endoderm. mom-1, mom-2, and mom-3 are required
      in the signaling cell, P2, while mom-4 is required in EMS. P2 signaling
      downregulates an HMG domain protein, POP-1, in one EMS daughter. The sequence of
      mom-2 predicts that it encodes a member of the Wnt family of secreted
      glycoproteins, which in other systems activate HMG domain proteins. Defective
      mitotic spindle orientations in mom mutant embryos indicate that Wnt signaling
      influences cytoskeletal polarity in blastomeres throughout the early embryo.

PMID- 9288750
TI  - Wnt signaling and an APC-related gene specify endoderm in early C. elegans
      embryos.
AB  - In a 4-cell stage C. elegans embryo, signaling by the P2 blastomere induces
      anterior-posterior polarity in the adjacent EMS blastomere, leading to endoderm
      formation. We have taken genetic and reverse genetic approaches toward
      understanding the molecular basis for this induction. These studies have
      identified a set of genes with sequence similarity to genes that have been shown
      to be, or are implicated in, Wnt/Wingless signaling pathways in other systems.
      The C. elegans genes described here are related to wnt/wingless, porcupine,
      frizzled, beta-catenin/armadillo, and the human adenomatous polyposis coli gene,
      APC. We present evidence that there may be partially redundant inputs into
      endoderm specification and that a subset of these genes appear also to function
      in determining cytoskeletal polarity in certain early blastomeres.

PMID- 9288751
TI  - Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy.
AB  - The absence of dystrophin at the muscle membrane leads to Duchenne muscular
      dystrophy (DMD), a severe muscle-wasting disease that is inevitably fatal in
      early adulthood. In contrast, dystrophin-deficient mdx mice appear physically
      normal despite their underlying muscle pathology. We describe mice deficient for
      both dystrophin and the dystrophin-related protein utrophin. These mice show many
      signs typical of DMD in humans: they show severe progressive muscular dystrophy
      that results in premature death, they have ultrastructural neuromuscular and
      myotendinous junction abnormalities, and they aberrantly coexpress myosin heavy
      chain isoforms within a fiber. The data suggest that utrophin and dystrophin have
      complementing roles in normal functional or developmental pathways in muscle.
      Detailed study of these mice should provide novel insights into the pathogenesis
      of DMD and provide an improved model for rapid evaluation of gene therapy
      strategies.

PMID- 9288752
TI  - Skeletal and cardiac myopathies in mice lacking utrophin and dystrophin: a model
      for Duchenne muscular dystrophy.
AB  - Dystrophin is a cytoskeletal protein of muscle fibers; its loss in humans leads
      to Duchenne muscular dystrophy, an inevitably fatal wasting of skeletal and
      cardiac muscle. mdx mice also lack dystrophin, but are only mildly dystrophic.
      Utrophin, a homolog of dystrophin, is confined to the postsynaptic membrane at
      skeletal neuromuscular junctions and has been implicated in synaptic development.
      However, mice lacking utrophin show only subtle neuromuscular defects. Here, we
      asked whether the mild phenotypes of the two single mutants reflect compensation
      between the two proteins. Synaptic development was qualitatively normal in double
      mutants, but dystrophy was severe and closely resembled that seen in Duchenne.
      Thus, utrophin attenuates the effects of dystrophin deficiency, and the double
      mutant may provide a useful model for studies of pathogenesis and therapy.

PMID- 9288753
TI  - Neuropilin is a receptor for the axonal chemorepellent Semaphorin III.
AB  - Extending axons in the developing nervous system are guided to their targets
      through the coordinate actions of attractive and repulsive guidance cues. The
      semaphorin family of guidance cues comprises several members that can function as
      diffusible axonal chemorepellents. To begin to elucidate the mechanisms that
      mediate the repulsive actions of Collapsin-1/Semaphorin III/D (Sema III), we
      searched for Sema III-binding proteins in embryonic rat sensory neurons by
      expression cloning. We report that Sema III binds with high affinity to the
      transmembrane protein neuropilin, and that antibodies to neuropilin block the
      ability of Sema III to repel sensory axons and to induce collapse of their growth
      cones. These results provide evidence that neuropilin is a receptor or a
      component of a receptor complex that mediates the effects of Sema III on these
      axons.

PMID- 9288754
TI  - Neuropilin is a semaphorin III receptor.
AB  - The semaphorin family contains a large number of phylogenetically conserved
      proteins and includes several members that have been shown to function in
      repulsive axon guidance. Semaphorin III (Sema III) is a secreted protein that in
      vitro causes neuronal growth cone collapse and chemorepulsion of neurites, and in
      vivo is required for correct sensory afferent innervation and other aspects of
      development. The mechanism of Sema III function, however, is unknown. Here, we
      report that neuropilin, a type I transmembrane protein implicated in aspects of
      neurodevelopment, is a Sema III receptor. We also describe the identification of
      neuropilin-2, a related neuropilin family member, and show that neuropilin and
      neuropilin-2 are expressed in overlapping, yet distinct, populations of neurons
      in the rat embryonic nervous system.

PMID- 9288755
TI  - A novel family of putative pheromone receptors in mammals with a topographically
      organized and sexually dimorphic distribution.
AB  - Mammals have retained two functionally and anatomically independent collections
      of olfactory neurons located in the main olfactory epithelium and in the
      vomeronasal organ (VNO). Pheromones activate the VNO in order to elicit fixed
      action behaviors and neuroendocrine changes involved in animal reproduction and
      aggression. Differential screening of cDNA libraries constructed from individual
      rat VNO neurons has led to the isolation of a novel family of approximately 100
      genes encoding seven transmembrane receptors with sequence similarity with Ca2+
      sensing and metabotropic glutamate receptors. These genes are likely to encode a
      novel family of pheromone receptors. Patterns of receptor gene expression suggest
      that the VNO is organized into discrete and sexually dimorphic functional units
      that may permit segregation of pheromone signals leading to specific arrays of
      behaviors and neuroendocrine responses.

PMID- 9288756
TI  - A multigene family encoding a diverse array of putative pheromone receptors in
      mammals.
AB  - The vomeronasal organ of mammals is an olfactory sensory structure that detects
      pheromones. It contains two subsets of sensory neurons that differentially
      express G alpha(o) and G alpha(i2). By comparing gene expression in single
      neurons, we identified a novel multigene family that codes for a diverse array of
      candidate pheromone receptors (VRs) expressed by the G alpha(o)+ subset.
      Different VRs are expressed by different neurons, but those neurons are
      interspersed, suggesting a distributed mode of sensory coding. Chromosome mapping
      experiments suggest an evolutionary connection between genes encoding VRs and
      receptors for volatile odorants. However, a dramatically different structure for
      VRs and the existence of variant VR mRNA forms indicate that there are diverse
      strategies to detect functionally distinct sensory stimuli.

PMID- 9288757
TI  - hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in
      tumor cells and during immortalization.
AB  - Telomerase, the ribonucleoprotein enzyme that elongates telomeres, is repressed
      in normal human somatic cells but is reactivated during tumor progression. We
      report the cloning of a human gene, hEST2, that shares significant sequence
      similarity with the telomerase catalytic subunit genes of lower eukaryotes. hEST2
      is expressed at high levels in primary tumors, cancer cell lines, and telomerase
      positive tissues but is undetectable in telomerase-negative cell lines and
      differentiated telomerase-negative tissues. Moreover, the message is up-regulated
      concomitant with the activation of telomerase during the immortalization of
      cultured cells and down-regulated during in vitro cellular differentiation. Taken
      together, these observations suggest that the induction of hEST2 mRNA expression
      is required for the telomerase activation that occurs during cellular
      immortalization and tumor progression.

PMID- 9288758
TI  - Ancient missense mutations in a new member of the RoRet gene family are likely to
      cause familial Mediterranean fever. The International FMF Consortium.
AB  - Familial Mediterranean fever (FMF) is a recessively inherited disorder
      characterized by dramatic episodes of fever and serosal inflammation. This report
      describes the cloning of the gene likely to cause FMF from a 115-kb candidate
      interval on chromosome 16p. Three different missense mutations were identified in
      affected individuals, but not in normals. Haplotype and mutational analyses
      disclosed ancestral relationships among carrier chromosomes in populations that
      have been separated for centuries. The novel gene encodes a 3.7-kb transcript
      that is almost exclusively expressed in granulocytes. The predicted protein,
      pyrin, is a member of a family of nuclear factors homologous to the Ro52
      autoantigen. The cloning of the FMF gene promises to shed light on the regulation
      of acute inflammatory responses.

PMID- 9288759
TI  - Monoallelically expressed gene related to p53 at 1p36, a region frequently
      deleted in neuroblastoma and other human cancers.
AB  - We describe a gene encoding p73, a protein that shares considerable homology with
      the tumor suppressor p53. p73 maps to 1p36, a region frequently deleted in
      neuroblastoma and other tumors and thought to contain multiple tumor suppressor
      genes. Our analysis of neuroblastoma cell lines with 1p and p73 loss of
      heterozygosity failed to detect coding sequence mutations in remaining p73
      alleles. However, the demonstration that p73 is monoallelically expressed
      supports the notion that it is a candidate gene in neuroblastoma. p73 also has
      the potential to activate p53 target genes and to interact with p53. We propose
      that the disregulation of p73 contributes to tumorigenesis and that p53-related
      proteins operate in a network of developmental and cell cycle controls.

PMID- 9288760
TI  - Monoclonal antibodies to the extracellular domain of prostate-specific membrane
      antigen also react with tumor vascular endothelium.
AB  - Prostate-specific membrane antigen (PSMA), initially defined by monoclonal
      antibody (mAb) 7E11, is a now well-characterized type 2 integral membrane
      glycoprotein expressed in a highly restricted manner by prostate epithelial
      cells. 7E11 has been shown to bind an intracellular epitope of PSMA that, in
      viable cells, is not available for binding. Herein, we report the initial
      characterization of the first four reported IgG mAbs that bind the external
      domain of PSMA. Competitive binding studies indicate these antibodies define two
      distinct, noncompeting epitopes on the extracellular domain of PSMA. In contrast
      to 7E11, these mAbs bind to viable LNCaP cells in vitro. In addition, they show
      strong immunohistochemical reactivity to tissue sections of prostate epithelia,
      including prostate cancer. These mAbs were also strongly reactive with vascular
      endothelium within a wide variety of carcinomas (including lung, colon, breast,
      and others) but not with normal vascular endothelium. These antibodies should
      prove useful for in vivo targeting to prostate cancer, as well as to the vascular
      compartment of a wide variety of carcinomas.

PMID- 9288761
TI  - Cellular adhesion regulates p53 protein levels in primary human keratinocytes.
AB  - To gain insight into p53 tissue-specific regulatory pathways and biological
      activities, we investigated mechanisms that may account for the elevated levels
      of p53 protein in human foreskin keratinocytes, relative to levels in dermal
      fibroblasts in vitro. Here, we report that the loss of cell anchorage resulted in
      an approximately 5-fold decrease in p53 levels in keratinocytes, which was
      reversible upon reattachment of cells to a substratum. In contrast, fibroblasts
      did not exhibit such adhesion-dependent regulation of p53 protein. Furthermore,
      p53 function was attenuated in keratinocytes relative to fibroblasts. These
      results link p53 to cell adhesion pathways and may provide a molecular basis for
      epigenetic differences in the maintenance of genomic stability among normal cell
      types.

PMID- 9288762
TI  - Role for E2F in DNA damage-induced entry of cells into S phase.
AB  - Mammalian cells respond to ionizing radiation (IR) with transient cell cycle
      arrest and induction of apoptosis. Here we show that IR increases the expression
      of the E2F-1 transcription factor and the entry of cells into S phase. E2F-1
      transactivation function is inhibited by cyclin A-kinase to ensure orderly
      progression through S phase. However, in contrast to proliferating cells, IR
      treatment results in down-regulation of cyclin A-kinase. Expression of a dominant
      negative form of the E2F heterodimeric partner DP-1 confirmed the involvement of
      E2F in IR-induced S-phase entry. These findings also support opposing signals
      involving the induction of E2F and the down-regulation of cyclin A-kinase in the
      IR response.

PMID- 9288763
TI  - 1,4-phenylenebis(methylene)selenocyanate exerts exceptional chemopreventive
      activity in rat tongue carcinogenesis.
AB  - Among the organoselenium compounds, 1,4-phenylenebis(methylene) selenocyanate (p
      XSC) is reported to exert the most effective chemopreventive effect on chemically
      induced carcinogenesis in the mammary glands, colon, and lung of laboratory
      animals. This study was designed to test the inhibitory effects of dietary p-XSC
      (5 and 15 ppm as selenium) during the initiation phase (1 week before, during,
      and up to 1 week after the carcinogen exposure) and the postinitiation phase (1
      week after carcinogen administration until termination) on the formation of
      neoplasms of the tongue induced in male F344 rats by 4-nitroquinoline-1-oxide (4
      NQO). The doses of p-XSC were 20% (5 ppm selenium) and 60% (15 ppm selenium) of
      maximum tolerated dose levels. At 6 weeks of age, all rats except those given p
      XSC alone and those in untreated groups were treated with 4-NQO (20 ppm in the
      drinking water for 8 weeks). Dietary p-XSC, administered at selenium levels of 5
      and 15 ppm during either the initiation or postinitiation phases, significantly
      reduced the incidence of carcinoma of the tongue. p-XSC was especially effective
      when it was administered at 15 ppm selenium during the postinitiation phase, in
      which case it completely inhibited the development of tongue carcinoma (from 47%
      in the dietary control to 0%). Glutathione S-transferase activities in the liver
      and tongue of rats treated with 4-NQO and p-XSC were significantly elevated
      compared to those in rats treated with 4-NQO alone. Similarly, quinone reductase
      activity was significantly elevated in the liver but decreased in the tongue
      (posterior portion). Such modulation by p-XSC in the phase II enzyme activities
      of the liver and tongue might be related to inhibition of the initiation. In
      addition, the expression of cell proliferation biomarkers, such as polyamine
      level, ornithine decarboxylase activity, 5-bromodeoxyuridin-labeling index, and
      argyrophilic nucleolar organizer's protein number, in the epithelium of the
      tongue was significantly reduced in rats that were fed thep-XSC diets compared to
      those who were fed the basal diet. Such alteration in cell proliferation through
      modulation of ornithine decarboxylase activity and polyamine biosynthesis in the
      tongue epithelium might be related to inhibition occurring in the postinitiation
      phase of carcinogenesis. The dose levels of p-XSC used induced no toxicity or
      alteration in body weight gain. Although the precise mechanisms of p-XSC-induced
      inhibition of tongue carcinogenesis remains to be elucidated, it is evident that
      p-XSC has powerful chemopreventive efficacy against tongue carcinogenesis.

PMID- 9288764
TI  - Inhibition of cytochromes P-450 and induction of glutathione S-transferases by
      sulforaphane in primary human and rat hepatocytes.
AB  - The isothiocyanate sulforaphane (SF) is thought to be a potential chemoprotective
      agent. Its effects on Phase I and Phase II enzymes of carcinogen metabolism in
      primary cultures of rat and human hepatocytes have been investigated. Northern
      blot analyses of rat hepatocytes showed a dose-dependent induction of mRNAs for
      rat glutathione S-transferases (rGSTs) A1/A2 and P1 but not M1. This was
      associated with enhanced levels of not only rGSTA1, A2, A4, A5, and P1 but also
      of rGSTs M1 and M2. On the other hand, the enzyme activities in rat hepatocytes
      associated with cytochromes P-450 (CYPs) 1A1 and 2B1/2, namely ethoxyresorufin-O
      deethylase and pentoxyresorufin-O-dealkylase, respectively, were decreased in a
      dose-dependent manner. In SF-treated human hepatocytes, hGSTA1/2 but not hGSTM1
      mRNAs were induced, and the expression of CYP1A2 was unaffected, whereas the
      expression of CYP3A4, the major CYP in human liver, was markedly decreased at
      both mRNA and activity levels. These observations demonstrate that in intact
      human and rat hepatocytes, SF may both induce a number of GSTs and cause enzyme
      inhibition of some but not all CYPs and, in the case of CYP3A4, inhibit both its
      enzyme activity and its expression.

PMID- 9288766
TI  - Mutation analysis of the putative tumor suppressor gene PTEN/MMAC1 in primary
      breast carcinomas.
AB  - A novel gene was identified recently at chromosome 10q23, named PTEN or MMAC1,
      and based on several criteria it was designated as a potential human tumor
      suppressor gene. Loss of heterozygosity affecting this region of 10q is observed
      in several cancer types, especially glioblastoma, and inactivating mutations of
      the PTEN/MMAC1 gene are found in some of these cancers as well as cell lines and
      xenografts. Breast cancer is among the tumor types in which mutations are
      documented, and germline mutations of the gene appear to be responsible for the
      rare autosomal dominant familial cancer syndrome known as Cowden disease, which
      includes breast cancer among its clinical features. To further determine the role
      that PTEN/MMAC1 mutations may play in breast tumorigenesis, the entire coding
      region was screened for mutations in 54 unselected primary breast cancers. Two
      mutations were identified, a somatic 2-bp deletion in an apparently sporadic
      breast cancer, and a germ-line 4-bp deletion in a breast cancer patient with a
      clinical history consistent with Cowden disease. These data indicate that somatic
      mutations of PTEN/ MMAC1 occur in only a small fraction of primary breast cancers
      and confirm the role of this gene in the etiology of Cowden disease. Evidence is
      also presented suggesting that numerous polymorphisms and missense variants exist
      in the PTEN/MMAC1 transcript.

PMID- 9288765
TI  - Fine mapping of a genetic locus for Peutz-Jeghers syndrome on chromosome 19p.
AB  - Peutz-Jeghers syndrome (PJS) was recently mapped in a single report to the
      telomeric region of chromosome 19p (A. Hemminki et al., Nat. Genet., 15: 87-90,
      1997). Our studies confirm this location and provide further localization of the
      PJS locus. In the five families examined, there were no recombinants with the
      marker D19S886. The multipoint log odds score at D19S886 is 7.52, and we found no
      evidence for genetic heterogeneity. We also found that all carriers expressed the
      PJS phenotype and no noncarriers displayed PJS sequellae, indicating complete
      penetrance with no sporadic cases.

PMID- 9288767
TI  - Disruption of the MMAC1/PTEN gene by deletion or mutation is a frequent event in
      malignant melanoma.
AB  - The MMAC1/PTEN gene, located at 10q23.3, is a candidate tumor suppressor commonly
      mutated in glioma. We have studied the pattern of deletion, mutation, and
      expression of MMAC1/PTEN in 35 unrelated melanoma cell lines. Nine (26%) of the
      cell lines showed partial or complete homozygous deletion of the MMAC1/PTEN gene,
      and another six (17%) harbored a mutation in combination with loss of the second
      allele. Mutations could also be demonstrated in uncultured tumor specimens from
      which the cell lines had been established, and cell lines derived from two
      different metastases from one individual carried the same missense mutation.
      Collectively, these findings suggest that disruption of MMAC1/PTEN by allelic
      loss or mutation may contribute to the pathogenesis or neoplastic evolution in a
      large proportion of malignant melanomas.

PMID- 9288768
TI  - Analysis of the FHIT gene and FRA3B region in sporadic breast cancer,
      preneoplastic lesions, and familial breast cancer probands.
AB  - The FHIT gene, which spans the FRA3B fragile site at chromosome 3p14.2, is a
      candidate tumor suppressor gene in breast and other cancers. We investigated FHIT
      and FRA3B for loss of heterozygosity (LOH); homozygous deletions; abnormal
      transcripts; and acquired/germ-line point mutations in breast cancer cell lines
      (n = 32), breast epithelial and stromal cell cultures (n = 18), microdissected
      invasive (n = 16) and ductal in situ carcinomas (n = 6), and their accompanying
      normal and abnormal epithelial foci (n = 14). LOH at 3p14.2, especially at FHIT
      intragenic marker D3S1300, was found in 6 of 16 microdissected invasive tumors
      and 3 of 6 ductal in situ carcinomas. In accompanying preneoplastic foci, LOH
      occurred in two of eight intraductal hyperplasias but not in histologically
      normal ductal epithelium (n = 6). Three of 32 (9%) breast cancer cell lines
      demonstrated homozygous deletions of FHIT exon 4 (two cases) and exon 5 (one
      case), which correlated with exon 4-deleted transcripts and loss of the cDNA
      transcript containing the coding exons 5-9, respectively. Normal mammary cultures
      and 31 of 32 tumor cell lines (97%) expressed wild-type coding transcripts as
      well as a minor exon 8-deleted message. Single-strand conformation polymorphism
      analysis of the coding exons in the 32 tumor and 18 normal breast cell lines and
      their sequencing revealed four silent polymorphisms and a germ-line histidine
      triad point mutation (651 G-->T) in a tumor arising in a 70-year-old woman. This
      mutation was also present in one of her two thus far unaffected daughters.
      Analysis of additional DNAs from 280 probands of high-risk breast cancer families
      for other FHIT exon 8 mutations detected an intronic point mutation 13 bases
      upstream of exon 8. Thus, we have demonstrated relatively early abnormalities of
      the FHIT/FRA3B region in breast cancer and discovered two rare FHIT germ-line
      mutations. The expression of a transcript containing the coding exons in nearly
      all cell lines, including those with germ-line mutations, suggests the
      possibility that another gene in the FRA3B region may be involved in the
      pathogenesis of breast cancer.

PMID- 9288770
TI  - Methylation hot spots in the 5' flanking region denote silencing of the O6
      methylguanine-DNA methyltransferase gene.
AB  - The mechanism whereby the DNA repair protein O6-methylguanine-DNA
      methyltransferase (MGMT) is silenced in repair-deficient (Mer-) human tumor cells
      is unknown. The role of methylation of the 5' CpG island in MGMT gene suppression
      is controversial. Although we previously showed by restriction enzyme analysis
      that CpG methylation in this region was associated with gene suppression,
      methylation at such sites was generally incomplete, suggesting heterogeneity. To
      clarify this issue, we have unequivocally defined the methylation status of every
      CpG by genomic sequencing of individual cloned copies of bisulfite-modified DNA.
      The region from -249 to +259 at the transcription start site was virtually
      methylation free in HT29 cells (Mer+), whereas in BE or HeLa S3 cells (Mer-),
      this region was substantially methylated in every DNA copy, with "hot spots" from
      -249 to -103 and from +107 to +196. Up-regulation of MGMT in HeLa S3 cells
      induced by 5-azacytidine was accompanied by progressive demethylation and the
      appearance of totally unmethylated copies of DNA. We conclude that, in Mer-
      cells, the MGMT promoter contains specific CpG methylation hot spots that are
      tightly linked to and are potential markers of gene silencing.

PMID- 9288769
TI  - Differential messenger RNA and protein expression of the receptor for advanced
      glycosylated end products in normal lung and non-small cell lung carcinoma.
AB  - The receptor for advanced glycosylated end products (RAGE), a member of the
      immunoglobulin superfamily, was one of the cDNA subtraction clones that was found
      to be differentially expressed in human lung and the corresponding tumor tissue.
      In nine additional matched normal/tumor pairs, a strongly reduced or missing
      expression, not only on a transcriptional level but also on a protein level, was
      demonstrated in the non-small cell lung carcinoma tissue. Because amphoterin, a
      physiological ligand of RAGE that is highly expressed in the lung, mediates cell
      differentiation via RAGE, a down-regulation of the receptor may be considered as
      a critical step in lung tumor formation. Furthermore, we determined the complete
      reading frame of RAGE.

PMID- 9288771
TI  - Does oral contraceptive use increase the risk of breast cancer in women with
      BRCA1/BRCA2 mutations more than in other women?
AB  - We conducted a study to determine whether the risk of breast cancer associated
      with oral contraceptive (OC) use is higher in women with BRCA1/BRCA2 mutations
      than in other women by examining whether breast cancer patients with these
      mutations were more likely than breast cancer patients without mutations in
      BRCA1/BRCA2 to have used OCs. We tested for BRCA1 185delAG and 5382insC and BRCA2
      6174delT mutations in a population-based sample of 50 young Ashkenazi Jewish
      breast cancer patients. Nine patients (18%) had a BRCA1 mutation, and five
      patients (10%) had a BRCA2 mutation. Long-term OC use (>48 months) before a first
      full-term pregnancy was associated with an elevated risk of being classified as a
      mutBRCA carrier (odds ratio, 7.8; trend, P = 0.004). The results suggest that OC
      use may increase the risk of breast cancer more in mutBRCA carriers than in
      noncarriers; however, they must be interpreted with caution given the small
      sample size.

PMID- 9288772
TI  - Ultraviolet radiation A-induced precursors of cutaneous melanoma in Monodelphis
      domestica.
AB  - Two groups of 30 dorsally shaved opossums (Monodelphis domestica) were exposed
      three times per week for 81 weeks to 250 J/m2 of UV radiation from FS40 sunlamps
      (approximately 150 J/m2 of UV radiation B; UV-B), or to 2.5 x 10(4) J/m2 of UV
      radiation A (UV-A) from filtered F40BLB fluorescent lamps (black lights). Animals
      were monitored for the appearance of nonmelanoma skin tumors (NMSTs) and
      melanocytic hyperplasia (MH). After 81 weeks of exposures, the prevalence of
      NMSTs was 71% and 4% for animals exposed to UV-B and UV-A, respectively. The
      difference between the treatment groups was statistically significant (P <
      0.001). However, the prevalence of MH in the treatment groups, 31% for UV-B
      exposed animals and 22% for UV-A-exposed animals, was not significantly different
      (P > 0.05). Thus, a dose of UV-A that was relatively ineffective in producing
      NMSTs, compared to UV-B, was as effective as UV-B in the induction of MH. If, as
      shown previously, MH is the precursor lesion for melanoma in this model, these
      results suggest that the action spectra for the induction of melanoma and NMSTs
      in the opossum are different.

PMID- 9288773
TI  - Regulation of mevalonate synthesis in rat mammary glands by dietary n-3 and n-6
      polyunsaturated fatty acids.
AB  - It is well established that dietary n-6 polyunsaturated fatty acids (PU-FAs)
      enhance rat mammary tumor development whereas n-3 PUFAs inhibit it, yet the
      mechanisms are unclear. The objective of this study was to investigate a
      mechanism by which n-3 and n-6 PUFAs could modulate mammary carcinogenesis.
      Female Sprague Dawley rats were fed diets containing either menhaden (n-3) or
      safflower oil (n-6) in a 7% fat diet for 1 week. In comparison to the n-6 diet,
      the n-3 diet significantly reduced the activity and levels of 3-hydroxy-3
      methylglutaryl CoA (HMG-CoA) reductase in mammary glands, thereby suppressing the
      formation of mevalonate. In addition to being essential for cholesterol
      biosynthesis, mevalonate is also required for DNA synthesis and may be involved
      in malignant transformation. Serum cholesterol was lower in the n-3 group than in
      the n-6 group (1.91 +/- 0.18 versus 2.61 +/- 0.37 mM; P < 0.01). Extrahepatic
      tissues meet most of their cholesterol requirements from circulating cholesterol,
      and the internalized cholesterol down-regulates HMG-CoA reductase. Thus, the
      concomitant decrease in serum cholesterol and mammary gland HMG-CoA reductase
      levels suggests that changes in circulating cholesterol levels do not solely
      determine the activity of extrahepatic reductase. We conclude that the mevalonate
      pathway may be a mechanism through which different types of dietary fat modulate
      breast cancer development.

PMID- 9288774
TI  - Growth of human nondiploid primary prostate tumor epithelial cells in vitro.
AB  - Research into molecular and cellular defects underlying prostate cancer would be
      advanced by in vitro models of prostate tumor cells representing patient tumors.
      We have propagated, in serum-free medium, epithelial cell cultures derived from
      nondiploid prostate tumors and normal human prostate. The serial passage tumor
      cells exhibited nondiploid karyotype and transformed phenotypes of focus
      formation and anchorage-independent growth. In contrast, the normal prostate
      cells showed diploid karyotype and lacked transformed phenotypes. Both the tumor
      and normal cells were positive for prostate-specific antigen and cytokeratins 18
      and 19 and negative for keratin 15. These results demonstrate that the nondiploid
      prostate tumors and normal prostate epithelial cell cultures retained their
      respective in vivo properties and should allow studies to elucidate molecular
      alterations involved in human prostate cancer.

PMID- 9288775
TI  - CREB-binding protein and p300/CBP-associated factor are transcriptional
      coactivators of the p53 tumor suppressor protein.
AB  - The structurally related transcriptional coactivators p300 and CBP possess
      histone acetyltransferase activity and associate with P/CAF, which is also a
      histone acetyltransferase. CBP and p300 have properties of tumor suppressor
      proteins; their interaction with P/CAF is disrupted by the adenoviral E1A
      oncoprotein, and the genes encoding CBP and p300 are mutated in human cancer. We
      observed a physical interaction between the transactivation domain of the p53
      tumor suppressor protein and CBP. Furthermore, CBP and P/CAF enhanced the ability
      of p53 to activate expression of the endogenous p21(cip1/waf1) gene, whereas E1A
      and dominant negative CBP mutants suppressed p53-dependent p21(cip1/waf1)
      expression. These studies link two tumor suppressor families and provide a
      framework for understanding the molecular mechanism by which p53 activates
      transcription.

PMID- 9288776
TI  - Induction of caspase-3 protease activity and apoptosis by butyrate and
      trichostatin A (inhibitors of histone deacetylase): dependence on protein
      synthesis and synergy with a mitochondrial/cytochrome c-dependent pathway.
AB  - The induction of apoptosis of tumor cells by the colonic fermentation product
      butyrate is thought to be an important mechanism in protection against colorectal
      cancer. Because a major action of butyrate is to inhibit histone deacetylase
      (leading to chromatin relaxation and altered gene expression), butyrate may
      induce apoptosis by derepression of specific cell death genes. Here we show that
      butyrate and trichostatin A (a more selective inhibitor of histone deacetylase)
      induce the same program of apoptosis in Jurkat lymphoid and LIM 1215 colorectal
      cancer cell lines that is strictly dependent on new protein synthesis (within 10
      h) and that leads to the conversion of the proenzyme form of caspase-3 to the
      catalytically active effector protease (within 16 h) and apoptotic death (within
      24 h). Cells primed with a low concentration of butyrate that itself did not
      induce activation of caspase-3 or apoptosis were, nevertheless, rendered highly
      susceptible to induction of apoptosis by staurosporine (an agent that has
      recently been shown to act by causing mitochondrial release of cytochrome c).
      Synergy between butyrate and staurosporine was due to the presence of a factor in
      the cytosol of butyrate-primed cells which enhanced over 7-fold the activation of
      caspase-3 induced by the addition of cytochrome c and dATP to isolated cytosol.
      We propose that changes at the level of chromatin structure, induced by a
      physiological substance butyrate, lead to the expression of a protein that
      facilitates the pathway by which mitochondria activate caspase-3 and trigger
      apoptotic death of lymphoid and colorectal cancer cells.

PMID- 9288777
TI  - Identification of a new P-glycoprotein-like ATP-binding cassette transporter gene
      that is overexpressed during hepatocarcinogenesis.
AB  - The liver is remarkably insensitive to a variety of cytotoxins and expresses a
      number of known drug resistance genes. To isolate new P-glycoprotein (Pgp)
      related genes, we screened a normal rat liver cDNA library at low stringency with
      a MDR1 cDNA fragment containing the P-loop and ATP binding site. We isolated a
      novel cDNA closely related to the Pgps that is dramatically increased in hepatic
      neoplasia and refer to it as P-glycoprotein-related protein (PRP). The predicted
      protein shows PRP to be a member of the ATP-Binding Cassette (ABC) family of
      proteins, and a multisequence comparison of the nucleotide binding domain and the
      ABC family signature sequences reveals that PRP sequences are highly conserved
      with the greatest similarity to the yeast heavy metal transporter encoded by
      hmtl. However, the hydropathy plot analysis suggests that PRP does not have any
      prominent membrane-spanning domains and thus is not typical of ABC transporters.
      The PRP transcript is detected in many normal tissues. In the H35 hepatoma cell
      line, PRP was overexpressed compared to normal liver. Southern blot analysis of
      DNA from the H35 rat hepatoma cells reveals that the PRP gene was amplified
      compared to normal liver. The orotic acid model of hepatocarcinogenesis was used
      to determine if during stepwise progression to liver cancer, PRP changed with
      hepatocarcinogenesis. At the hyperplastic nodule stage, PRP expression was
      increased over its expression in normal surrounding liver. More dramatic
      increases in PRP expression were found in frank hepatic carcinomas. Cumulatively,
      these studies are the first to link a novel ABC family member to the hepatic
      neoplastic process, a role that may be recapitulated in other cells, considering
      the ubiquitous expression of PRP.

PMID- 9288779
TI  - Comparison of estrogen receptor DNA binding in untreated and acquired
      antiestrogen-resistant human breast tumors.
AB  - Preliminary studies have suggested that measuring the ability of immunoreactive
      67-kDa estrogen receptor (ER) to bind DNA and form in vitro complexes with its
      cognate estrogen response element (ERE) might serve to identify breast tumors
      most likely to respond to antiestrogens like tamoxifen. Data from two different
      surveys of untreated primary breast tumors confirmed that only 67% (74 of 111) of
      ER-positive tumors express a receptor capable of forming ER-ERE complexes by gel
      shift assay, with tumors of lower ER content having significantly reduced ER DNA
      binding frequency (56%) relative to those of higher ER content (82%; P = 0.007).
      In contrast to these untreated tumors, a panel of 41 receptor-positive breast
      tumors excised after acquiring clinical resistance to tamoxifen during either
      primary (n = 26) or adjuvant therapy (n = 15) showed a significantly greater ER
      DNA-binding frequency, with nearly 90% capable of forming ER-ERE complexes (P <
      0.02). To assess experimentally whether ER DNA-binding function is altered during
      the development of antiestrogen resistance, nude mouse MCF-7 tumor xenografts
      were analyzed before and after the acquisition of in vivo resistance to either
      tamoxifen or a pure steroidal antiestrogen, ICI 182,780. Tamoxifen-resistant MCF
      7 tumors retained full expression of 67-kDa DNA-binding ER, and despite a
      markedly reduced ER content in the ICI 182,780-treated tumors, the expressed ER
      in these antiestrogen-resistant tumors exhibited full ability to form ER-ERE
      complexes. These findings indicate that breast tumors with acquired antiestrogen
      resistance continue to express ER of normal size and DNA-binding ability and
      suggest that the failure of antiestrogens to arrest tumor growth during emergence
      of clinical resistance results from an altered gene-regulatory mechanism(s) other
      than ER-ERE complex formation.

PMID- 9288778
TI  - Enhancement of experimental colon cancer by genistein.
AB  - Several phytochemicals and micronutrients that are present in fruits and
      vegetables are known to exert cancer chemopreventive effects in several organs,
      including the colon. Among them, the soybean isoflavonoid genistein received much
      attention due to its potential anticarcinogenic, antiproliferative effects and
      its potential role in several signal transduction pathways. The present study was
      designed to investigate the effect of genistein on azoxymethane (AOM)-induced
      colon carcinogenesis and to study its modulatory role on the levels of activity
      of 8-isoprostane, cyclooxygenase (COX), and 15-hydroxyprostaglandin F2alpha
      dehydrogenase (15-PGDH) in the colonic mucosa and colon tumors of male F344 rats.
      At 5 weeks of age, groups of male F344 rats were fed control (AIN-76A) diet or a
      diet containing 250 ppm genistein. Beginning 2 weeks later, all animals except
      those in the vehicle-treated groups were given weekly s.c. injections of AOM (15
      mg/kg body weight) for 2 successive weeks. All rats were continued on their
      respective dietary regimen for 52 weeks after AOM treatment and were then
      sacrificed. Colon tumors were evaluated histopathologically. Colonic mucosae and
      tumors were analyzed for COX, 15-PGDH, and 8-isoprostane levels. Administration
      of genistein significantly increased noninvasive and total adenocarcinoma
      multiplicity (P < 0.01) in the colon, compared to the control diet, but it had no
      effect on the colon adenocarcinoma incidence nor on the multiplicity of invasive
      adenocarcinoma (P > 0.05). Also, genistein significantly inhibited the 15-PGDH
      activity (>35%) and levels of 8-iosoprostane (50%) in colonic mucosa and in
      tumors. In contrast, genistein had no significant effect on the COX synthetic
      activity, as measured by the rate of formation of prostaglandins and thromboxane
      B2 from [14C]arachidonic acid. The results of this investigation emphasize that
      the biological effects of genistein may be organ specific, inhibiting cancer
      development in some sites yet showing no effect or an enhancing effect on the
      tumorigenesis at other sites, such as the colon. The inhibition of 8-isoprostane
      levels by genistein indicates its possible antioxidant potential, which is
      independent of the observed colon tumor enhancement, yet this agent may also
      possess several biological effects that overshadow its antioxidant potential. The
      exact mechanism(s) of colon tumor enhancement by genistein remain to be
      elucidated; it is likely that its colon tumor-enhancing effects may, at least in
      part, be related to inhibition of prostaglandin catabolic enzyme activities.

PMID- 9288781
TI  - Development of antiangiogenin peptide using a phage-displayed peptide library.
AB  - Angiogenesis is essential for tumor growth and metastasis. Here, we have
      developed a peptide antagonist of human angiogenin, which is a potent and tumor
      associated angiogenic factor. ANI-E peptide was derived from the phage clone,
      which binds to angiogenin via the disulfide-constrained octapeptide epitope that
      is displayed on its surface, and is displaced by actin. Disulfide-constrained ANI
      E peptide inhibits the interaction of angiogenin with actin, which is regarded as
      the angiogenin-binding protein on the surface of endothelial cells, without any
      visible effect on the ribonucleolytic activity of angiogenin. The peptide also
      inhibits the neovascularization that is induced by angiogenin in the chick
      chorioallantoic membrane assay. The antiangiogenic activity of the peptide is
      specific for angiogenin because the peptide does not have any apparent effect on
      embryonic angiogenesis or the preexisting blood vessels. The disulfide bond and
      the glutamic acid inside the disulfide ring of ANI-E peptide are indispensable
      for its antiangiogenin activity. Furthermore, ANI-E peptide blocks the
      angiogenesis that is induced by the angiogenin-secreting PC3 human prostate
      adenocarcinoma cells, without any direct effect on the proliferation, as well as
      the adhesion of PC3 cells to angiogenin. Therefore, the inhibition of the tumor
      induced angiogenesis by ANI-E peptide is most likely caused by the neutralization
      of the extracellular angiogenin that is secreted by PC3 cells. On the basis of
      our results, ANI-E peptide may be effective for the treatment of various human
      tumors that secrete angiogenin. Our results also strongly support the hypothesis
      that the interaction of angiogenin with the cell surface actin-like protein is
      essential for the biological action of angiogenin, and angiogenin has an
      essential role in tumor-induced angiogenesis.

PMID- 9288780
TI  - Dichlorodiphenyltrichloroethane serum levels and breast cancer risk: a case
      control study from Mexico.
AB  - Some, but not all, epidemiological studies have suggested that
      dichlorodiphenyltrichloroethane (DDT) may play a role in the development of
      breast cancer. These investigations have been conducted in countries where this
      substance has been banned for at least 20 years. We conducted a study in Mexico,
      a country in which DDT is still being used to control malaria. In a hospital
      based case-control study, we compared 141 histologically confirmed cases of
      breast cancer with 141 age-matched controls (+/-3 years). All subjects were
      identified at three referral hospitals of Mexico City between March 1994 and
      April 1996. Reproductive histories and other variables were obtained by
      structured interviews, DDT/DDE levels were determined in serum by gas-liquid
      chromatography. The arithmetic mean of serum DDE in lipid basis was 562.48 +/-
      676.18 ppb (range, 10.24-4661.44) for the cases and 505.46 +/- 567.22 ppb (range,
      0.004 to 4361.75) for the controls, but this difference was not statistically
      significant. The age-adjusted odds ratios for breast cancer regarding the serum
      level of DDE were 0.69 (95% confidence interval, 0.38-1.24) and 0.97 (confidence
      interval, 0.55-1.70) for the contrasts between tertile 1 (lowest level) and
      tertiles 2 and 3, respectively. These estimates were unaffected by adjustment for
      body mass, accumulated time of breast-feeding and menopause, and other breast
      cancer risk factors. These results do not lend support to the hypothesis that DDT
      is causally related to breast cancer at the body-burden levels found in our study
      population but do not exclude the possibility that higher levels of exposure
      could still play a role in the etiology of this tumor.

PMID- 9288782
TI  - Inhibitors of epidermal growth factor receptor kinase and of cyclin-dependent
      kinase 2 activation induce growth arrest, differentiation, and apoptosis of human
      papilloma virus 16-immortalized human keratinocytes.
AB  - Human papilloma virus 16 (HPV 16) is associated with cervical cancer and is
      therefore considered a major health risk for women. Immortalization of
      keratinocytes induced by HPV infection is largely due to the binding of p53 and
      Rb by the the viral oncoproteins E6 and E7, respectively, and is driven to a
      large extent by a transforming growth factor alpha/amphiregulin epidermal growth
      factor receptor autocrine loop. In this study, we show that the growth of HPV 16
      immortalized human keratinocytes can be blocked by a selective epidermal growth
      factor receptor kinase inhibitor, AG 1478, and by AG 555, a blocker of cyclin
      dependent kinase 2 (Cdk2) activation. AG 1478 induces a massive increase in the
      Cdk2 protein inhibitors p27 and p21, whereas AG 555 appears to have a different
      mechanism of action, inhibiting the activation of Cdk2. Growth arrest induced by
      AG 1478 and AG 555 is accompanied by up to 20% of cells undergoing apoptosis.
      Following AG 1478 treatment but not AG 555 treatment, up to 50% of cells undergo
      terminal keratinocyte differentiation as determined by filaggrin expression and
      by the decline in the expression of cytokeratin 14. The growth-arresting
      properties of AG 1478 and AG 555 identifies them as possible lead antipapilloma
      agents.

PMID- 9288783
TI  - Microfilament depletion and circumvention of multiple drug resistance by
      sphinxolides.
AB  - Sphinxolides, a newly described family of cytotoxins from the New Caledonian
      sponge Neosiphonia superstes, bear structural resemblance to scytophycins. We now
      demonstrate that the cytotoxicity of sphinxolides is associated with cell cycle
      arrest in G2-M and induction of apoptosis. Like scytophycins and cytochalasins,
      sphinxolides caused rapid loss of microfilaments in cultured cells, without
      affecting microtubule organization. Microfilament reassembly was very slow after
      removal of the sphinxolide, consistent with the slow recovery of cellular
      proliferation. Sphinxolides potently inhibited actin polymerization in vitro and
      the microfilament-dependent ATPase activity of purified actomyosin, indicating a
      direct effect on actin. Importantly, sphinxolides were equally cytotoxic toward
      MCF-7 human breast carcinoma cells and a subline which overexpresses P
      glycoprotein (MCF-7/ADR). Similarly, overexpression of the multidrug resistance
      associated protein MRP by HL-60 cells did not confer resistance to the
      sphinxolides. These studies demonstrate that sphinxolides are potent new
      antimicrofilament compounds that circumvent multidrug resistance mediated by
      overexpression of either P-glycoprotein or MRP. Therefore, these agents may be
      useful in the treatment of drug-resistant tumors.

PMID- 9288784
TI  - Potentiation of cisplatin antitumor activity using a vitamin D analogue in a
      murine squamous cell carcinoma model system.
AB  - In a murine squamous cell carcinoma (SCC) model, we have demonstrated that both
      1,25-dihydroxycholecalciferol (1,25-D3) and the analogue 1,25-dihydroxy-16-ene-23
      yne-cholecalciferol (Ro23-7553) have significant in vitro and in vivo antitumor
      activity. We have examined here the cell cycle effect of 1,25-D3 and Ro23-7553 on
      SCCVII/SF tumor cells by quantitating nuclear DNA using a detergent-trypsin
      method via flow cytometry analysis. Both 1,25-D3 and Ro23-7553 resulted in a
      significant increase of cells in G0-G1, with an accompanying decrease of cells in
      S phase. The ability to arrest cells in G0-G1 has been exploited by combining
      Ro23-7553 with the cytotoxic agent cisplatin (cis-diamminodichloroplatinum;
      cDDP). Using the in vitro clonogenic assay, pretreatment with Ro23-7553 for 24-48
      h significantly enhanced cDDP-mediated tumor cell kill as compared to concurrent
      treatment with Ro23-7553 and cDDP or cDDP alone. To examine the effect of Ro23
      7553 and cDDP in vivo, C3H/HeJ mice with 9-14-day SCC tumors were treated either
      for 3 days with varying i.p. doses of Ro23-7553 or for 7 days continuously
      through the use of Alzet pumps, and on the last day of Ro23-7553 treatment, cDDP
      (1-6 mg/kg) was administered. Using the in vivo excision tumor cell clonogenic
      assay, in which tumors were removed from animals 24 h after cDDP treatment and
      plated in a clonogenic assay, pretreatment with Ro23-7553 markedly enhanced cDDP
      mediated clonogenic tumor cell kill, even at low doses of cDDP as compared to
      cDDP treatment alone. Similarly, a significant decrease in fractional tumor
      volume and increase in tumor regrowth delay was observed when animals were
      pretreated before cDDP with Ro23-7553 as compared to either agent alone. These
      results demonstrate a significant enhanced antitumor effect with Ro23-7553
      pretreatment before cDDP both in vitro and in vivo and suggest that Ro23-7553 may
      potentiate cDDP cytotoxicity through effects on cell cycle progression.

PMID- 9288785
TI  - Mutator phenotype in Msh2-deficient murine embryonic fibroblasts.
AB  - Embryonic fibroblast cell lines were established from mice deficient,
      heterozygous, or proficient for Msh2, one of the three known DNA mismatch repair
      genes involved in hereditary nonpolyposis colon cancer (HNPCC). Cell lines were
      established by transfection of primary mouse embryo fibroblasts with E7 and Ras
      oncogenes or mutant p53. Spontaneously immortalized cells derived from the
      primary cultures were also studied. To determine whether these cells developed a
      mutator phenotype similar to that found in colon cancer cells deficient in
      mismatch repair, we measured mutation rates, microsatellite instability, and
      sensitivities to a range of DNA-damaging agents. The mutator phenotype detected
      in the E7 and Ras or mutant p53-immortalized Msh2-/- mouse cells was similar to
      that found in human mismatch repair-deficient colorectal carcinoma cell lines.
      Mutation rates to ouabain resistance were increased 8-12-fold relative to lines
      from Msh2+/+ mice, and microsatellite instability was detectable in 12-18% of
      subclones derived from the Msh2-/- line but was undetectable in subclones
      developed from the Msh2+/+ line. Furthermore, E7 and Ras or spontaneously
      immortalized Msh2-/- cells were significantly more resistant to the cytotoxic
      effects of 6-thioguanine relative to Msh2+/+ cells. In contrast, these lines
      showed various responses to UV light and cis-platinum, suggesting that mismatch
      repair deficiency was not the sole determinant for sensitivity to these DNA
      damaging agents. Particular attention was paid to the properties of cells
      heterozygous for the Msh2 mutant gene, which would mimic the situation of an
      HNPCC carrier. However, our studies failed to reveal any properties of these
      cells that might provide a growth advantage or predispose them for the
      acquisition of further mutations. This observation is consistent with the model
      that inactivation of the wild-type Msh2 allele is a critical step for
      tumorigenesis in HNPCC patients.

PMID- 9288786
TI  - Expression and mutational analysis of the DCC, DPC4, and MADR2/JV18-1 genes in
      neuroblastoma.
AB  - Loss of heterozygosity (LOH) on chromosome 18q21 is found frequently in various
      human cancers. Three candidate tumor suppressor genes, DCC (deleted in colorectal
      carcinomas), DPC4 (deleted in pancreatic carcinomas, locus 4), and MADR2/JV18-1
      (MAD-related gene 2), have been cloned and identified from this chromosome
      region. We have reported recently that LOH on chromosome 18q is observed
      frequently in neuroblastoma. Alterations of DCC are involved in many human
      tumors. DPC4 and MADR2/JV18-1 are recently demonstrated to be altered in
      pancreatic and colorectal cancers, respectively. To confirm if inactivation of
      the DCC, DPC4, and MADR2/JV18-1 genes is involved in the pathogenesis of
      neuroblastoma and to clarify the mechanism of inactivation, we analyzed the
      expression of DCC, DPC4, and MADR2/JV18-1 in neuroblastoma cell lines and primary
      tumors by reverse transcription-PCR and investigated the mutations in the coding
      regions of these genes by PCR/reverse transcription-PCR single-strand
      conformation polymorphism. We found that 12 of 25 (48%) cell lines and 14 of 32
      (44%) primary tumors, including 3 with 18q LOH, had absent or reduced expression
      of DCC mRNA. Expression was more likely to be reduced in advanced (67%) than in
      early stage neuroblastomas (24%) (P = 0.036), suggesting that inactivation of the
      DCC gene plays an important role in the progression of neuroblastoma. Altered
      expression of DPC4 was found in six (24%) cell lines and six (19%) tumors.
      MADR2/JV18-1 expression was reduced or absent only in four (16%) cell lines and
      three (9%) tumors. Mutations of the DCC genes were examined in 25 of 29 exons in
      neuroblastoma cell lines, and those exons in which mutations were found were
      further examined in primary tumors. We found missense mutations of AAC (Asn) to
      AGC (Ser) at DCC codon 176 in one cell line and ACC (Thr) to ATC (Ile) at codon
      1105 in one cell line and tumor, respectively; polymorphisms of CGA (Arg) to GGA
      (Gly) at codon 201 and TTT (Phe) to TTG (Leu) at codon 951 in most of the cell
      lines and tumors; and a silent mutation of GAG (Glu) to GAA (Glu) at codon 118 in
      four cell lines and five primary tumors. We did not identify any mutations in the
      DPC4 and MADR2/JV18-1 genes in neuroblastoma. Our results suggested that
      mutations of the DCC gene may be involved in the pathogenesis of neuroblastomas
      but failed to account for the relatively high frequency of the altered
      expression, implying that other mechanisms are responsible for the inactivation
      of the DCC gene in neuroblastoma. Low frequency of reduced or absent mRNA
      expression and lack of mutations in DPC4 and MADR2/JV18-1 genes suggested a
      limited role for these two genes in neuroblastoma.

PMID- 9288787
TI  - Localization of SMAD5 and its evaluation as a candidate myeloid tumor suppressor.
AB  - Acquired interstitial or complete losses of chromosome 5 are recurring anomalies
      associated with preleukemic myelodysplasia and acute myelogenous leukemia with a
      poor prognosis. Previous studies have delineated a potential myeloid tumor
      suppressor locus to a <2.4-Mb interval between the genes for IL9 and EGR1 on
      5q31. In this report, we have localized the SMAD5 gene, a homologue of the tumor
      suppressor genes SMAD4/DPC-4 and SMAD2/JV18.1, to the minimal myeloid tumor
      suppressor locus and characterized its open reading frame and genomic
      organization. SMAD5 transcripts are readily detectable in hematolymphoid tissues
      and leukemic blasts. Absence of intragenic mutations in the remaining SMAD5
      allele of leukemic patients and multiple solid tumor cell lines prescreened for
      loss of heterozygosity suggests that SMAD5 may not be a common target of somatic
      inactivation in malignancy.

PMID- 9288788
TI  - Differential involvement of the human mismatch repair proteins, hMLH1 and hMSH2,
      in transcription-coupled repair.
AB  - Defects in DNA mismatch repair have been associated with both hereditary and
      sporadic forms of cancer. Recently, it has been shown that human cell lines
      deficient in mismatch repair were also defective in the transcription-coupled
      repair (TCR) of UV-induced DNA damage. We examined whether TCR of ionizing
      radiation-induced DNA damage also requires the genes involved in DNA mismatch
      repair. Cells defective in the hMSH2 gene were deficient in the removal of
      oxidative damage, including thymine glycols, from the transcribed strand of an
      active gene. However, an hMLH1 mutant showed normal levels of TCR. By comparison,
      defects in either hMSH2 or hMLH1 resulted in reduced TCR of UV damage.
      Introducing chromosomes carrying either hMSH2 or hMLH1 into these cell lines
      restored their ability to carry out TCR. Deficiencies in either hMSH2 or hMLH1
      did not result in decreased overall genomic levels of repair or lead to an
      increased sensitivity to either UV or ionizing radiation. Our results provide the
      first evidence for a protein that is absolutely required for the preferential
      removal of UV-induced DNA damage but not oxidative DNA damage from the
      transcribed strand of an active human gene.

PMID- 9288789
TI  - Rapid detection of specific messenger RNAs in thyroid carcinomas by reverse
      transcription-PCR with degenerate primers: specific expression of oncofetal
      fibronectin messenger RNA in papillary carcinoma.
AB  - The search for mRNAs that are specifically expressed in cancer tissues is
      important for gene diagnosis and therapy. However, finding such mRNAs in human
      cancers is usually very difficult, both because of the limited volume of RNA
      obtainable from the tissues and the many technical difficulties of RNA analysis.
      To address these problems, the present study compared mRNA from thyroid cancer
      tissues with those from normal and benign tissues by reverse transcription-PCR
      using two degenerate primers. Amplified cDNAs were separated by electrophoresis
      with nondenaturing acrylamide gel, then three bands that are increased in cancer
      tissues were selected, reamplified by PCR, and cloned into T-vector. One of the
      bands was determined by sequencing analysis to be oncofetal fibronectin. The
      expression of oncofetal fibronectin mRNA in benign and malignant tissues was
      examined by Northern blot and reverse transcription-PCR using specific primers of
      its cDNA sequence, and its increased expression was observed only in papillary
      and anaplastic carcinomas. Thus, the present method rapidly detected specific
      mRNAs in cancer tissues, and one of these, oncofetal fibronectin mRNA, is a good
      target for gene diagnosis of papillary carcinoma.

PMID- 9288791
TI  - Neu differentiation factor induces ErbB2 down-regulation and apoptosis of ErbB2
      overexpressing breast tumor cells.
AB  - Neu differentiation factor (NDF), a member of the epidermal growth factor (EGF)
      related peptide family, activates ErbB2 via heterodimerization with the NDF
      receptors ErbB3 and ErbB4. In a similar fashion, EGF receptor (EGFR) agonists
      induce heterodimers of EGFR and ErbB2. In this paper, we show that the ErbB2
      overexpressing breast tumor cells SKBR3, AU565, and MDA-MB453 are growth
      inhibited by NDF. Cells with elevated levels of ErbB2 but little or no NDF
      receptors (SKOV3 and MDA-MB361) or cells with low levels of ErbB2 (T47D and MCF7)
      are not growth inhibited. None of the EGFR agonists tested (EGF, beta-cellulin,
      or heparin-binding EGF) inhibited growth of ErbB2-overexpressing cells. These
      results suggest that formation of an ErbB2/NDF receptor heterodimer, but not of
      an ErbB2/EGFR heterodimer, promotes growth inhibition. In addition, NDF caused a
      down-regulation of ErbB2 but not of ErbB3. The mechanism underlying the
      inhibitory effect was examined further in SKBR3 cells, which are 95% growth
      inhibited by NDF. A G2-M arrest is seen 24 h after NDF treatment, and increased
      apoptosis is detectable from day 2 onward. The results demonstrate for the first
      time that NDF induces apoptosis of tumor cells overexpressing ErbB2.

PMID- 9288790
TI  - Genomic DNA-based hMSH2 and hMLH1 mutation screening in 32 Eastern United States
      hereditary nonpolyposis colorectal cancer pedigrees.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant cancer
      syndrome characterized by early age of onset colorectal cancer (mean 45 years) as
      well as endometrial, urinary tract, and upper gastrointestinal adenocarcinomas.
      The HNPCC phenotype has been shown to segregate with germline mutations in the
      human homologues of the DNA mismatch repair genes MSH2, MLH1, PMS1, and PMS2.
      However, the majority of published DNA mismatch repair gene mutation surveys
      associated with HNPCC kindreds report multiple levels of preselection, including
      2p and 3p chromosomal linkage analysis and the evaluation of microsatellite
      instability of proband colorectal cancers prior to mutation analysis. For this
      reason, the concise contribution of each of the known DNA mismatch repair genes
      to the HNPCC phenotype remains unknown. We report the results of a genomic DNA
      based analysis of hMSH2 and hMLH1 germline mutations in 32 unrelated Eastern
      United States HNPCC kindreds. These families were selected for study on the basis
      of phenotype only. We identified three hMSH2 and six hMLH1 mutations in eight
      families, for a positive mutation rate of 25%. Two mutations were identified in
      one of the families. Four of the mutations detected have not been reported in the
      literature previously. One of the mutation-positive families is African American;
      the others were of European-American ancestry. These results provide a
      clarification of the contribution of hMSH2 and hMLH1 to the HNPCC phenotype and
      suggest that in the majority of Eastern United States HNPCC kindreds selected by
      phenotype alone, the molecular genetic basis for the disease remains unknown.

PMID- 9288792
TI  - An epitope on VLA-6 (alpha6beta1) integrin involved in migration but not adhesion
      is required for extravasation of murine melanoma B16F1 cells in liver.
AB  - VLA-6 (alpha6beta1) integrin represents the major receptor for interaction with
      laminin substrate. It has been proposed that VLA-6 mediates tumor cell adhesion
      to the endothelium during extravasation. We have further explored this
      possibility using mouse melanoma B16F1 cells, which express VLA-6 as the
      principal laminin receptor, and two VLA-6 monoclonal antibodies (mAbs), MA6 and
      GoH3. Adhesion is a prerequisite of cell movement on matrix proteins. Thus, GoH3,
      which inhibited VLA-6-mediated adhesion, blocked cell movement on laminin. The
      recently prepared alpha6 integrin-specific mAb MA6 bound to an epitope in close
      proximity to GoH3, but it had no effect on VLA-6-mediated cell adhesion. We
      report here that although MA6 did not affect adhesion, it blocked mouse melanoma
      B16F1 cell movement on laminin to the same extent as GoH3. Results therefore
      demonstrate an active role of VLA-6 in providing cell movement as well as the
      initial adhesive event on laminin. In addition, mAb MA6 had no effect on the
      induction of tyrosine phosphorylation of focal adhesion kinase upon adhesion of
      B16F1 cells to laminin. Therefore, inhibition of cell movement by MA6 involved
      mechanism(s) other than an interference of VLA-6 signaling events leading to
      phosphorylation of focal adhesion kinase. The epitopes of GoH3 and MA6 may
      represent spatially and temporally related sites on VLA-6 that are involved
      during cell movement, or, alternatively, MA6 may inhibit the interaction of VLA-6
      with associated cell surface molecules required for cell movement. In vivo
      videomicroscopy experiments also revealed that an inhibition of VLA-6 migratory
      function by MA6 resulted in a reduction in the ability of B16F1 to extravasate
      during hematogenous metastasis in the liver.

PMID- 9288793
TI  - Paclitaxel- and docetaxel-dependent activation of CA-125 expression in human
      ovarian carcinoma cells.
AB  - Taxanes represent a new class of antineoplastic agents that are being evaluated
      in several malignant tumors; they have been shown to induce a high remission rate
      and to prolong survival in ovarian cancer patients. However, CA-125 has been
      suggested to be an unreliable marker for monitoring response to paclitaxel
      therapy. Therefore, we were interested in whether taxanes may directly modulate
      CA-125 expression. Human ovarian carcinoma cell lines OVCAR-3, HOC-7, SKOV-6,
      2780, 2774, and HTB-77 were treated with paclitaxel or docetaxel. Secreted,
      surface-associated, and cytosolic CA-125 were estimated by means of a sandwich
      solid-phase RIA or by immuno-flow cytometry. In addition to in vitro
      antiproliferative activity, paclitaxel and docetaxel augmented the expression of
      the tumor marker CA-125 in the three ovarian carcinoma cell lines, OVCAR-3, HOC
      7, and SKOV-6, constitutively expressing this tumor marker. The three CA-125
      negative cell lines, 2780, 2774, and HTB-77, did not respond to taxane treatment
      by expressing this tumor marker, although their proliferation was markedly
      inhibited. The taxane-mediated induction of CA-125 was found to be dependent on
      intact protein and RNA biosynthesis. However, CA-125 concentration was increased
      in the supernatant medium only and not on cell surface or cytosol. Our results
      demonstrate an in vitro activation of ovarian carcinoma cells in terms of CA-125
      secretion by taxanes. This may explain the CA-125 fluctuations observed in vivo
      under paclitaxel treatment and may indicate that CA-125 is not a reliable tumor
      marker during taxane chemotherapy.

PMID- 9288794
TI  - The CD95 (APO-1/Fas) system mediates drug-induced apoptosis in neuroblastoma
      cells.
AB  - Anticancer agents have been shown to trigger apoptosis in chemosensitive tumors
      such as neuroblastomas. We previously identified activation of the CD95 system as
      one of the key mechanisms for doxorubicin-induced apoptosis in leukemic T cells.
      Here, we report that therapeutic concentrations of doxorubicin, cisplatinum, and
      VP-16 led to induction of CD95 receptor and CD95 ligand (CD95-L) that mediated
      cell death in chemosensitive neuroblastoma cells. Using F(ab')2 anti-CD95
      antibody fragments to interfere with CD95-L-receptor interaction markedly reduced
      apoptosis induced by those drugs in vitro. Cyclosporin A inhibited induction of
      CD95 mRNA and CD95-L mRNA and blocked drug-mediated apoptosis. Drug-induced
      apoptosis involved activation of caspases (interleukin 1beta-converting
      enzyme/Ced-3-like proteases) and processing of the prototype caspase substrate
      PARP and was completely blocked by benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl
      ketone, a peptide inhibitor of caspases. In addition, neuroblastoma cells that
      were resistant to CD95-triggered apoptosis also displayed cross-resistance to
      chemotherapeutic agents. These data provide new clues for understanding the
      molecular requirements for drug-induced apoptosis in chemosensitive neuroblastoma
      cells by demonstrating that cell death was mediated via the CD95-L-receptor
      system and may open new avenues for targeting drug resistance of neuroblastoma.

PMID- 9288795
TI  - The biosynthesis and secretion of prostate-specific antigen in LNCaP cells.
AB  - Prostate-specific antigen (PSA) has been demonstrated to release the active form
      of insulin-like growth factor I in vitro (P. Cohen et al., J. Clin. Endocrinol. &
      Metab., 75: 1046-1053, 1992; P. Cohen et al., J. Clin. Endocrinol. & Metab., 79:
      1410-1415, 1994; P. Cohen et al., Horm. Metab. Res., 26: 81-84, 1994) and has
      significant mitogenic activity on osteoblast cells, fibroblasts, and other
      cultured cells (C. S. Killian et al., Biochem. Biophys. Res. Commun., 192: 940
      947, 1993). Recently, PSA has been found not only in prostate tissues but also in
      breast, colon, ovarian, and other tissues (E. P. Diamandis and H. Yu, J. Clin.
      Endocrinol. & Metab., 80: 1515-1517, 1995; E. P. Diamandis and H. Yu, Clin.
      Chem., 41: 204-210, 1995; A. Clements and A. Mukhtar, J. Clin. Endocrinol. &
      Metab., 78: 1536-1539, 1994). Therefore, PSA has been proposed as a candidate
      growth factor, cytokine, or growth factor regulator. In this setting, knowing how
      to manipulate or block the secretion of PSA by the prostate cancer cells could be
      a useful approach to controlling the progression of human prostate cancers. Using
      metabolic labeling experiments, we have studied the biosynthesis and secretion of
      PSA in LNCaP cells. We have also examined the effects of DTT, tunicamycin, 1
      deoxymannojirimycin, pilocarpine, and testosterone on PSA biosynthesis and
      secretion. The results indicate that the secretion of PSA in LNCaP cells is
      constitutive instead of regulated and that the disruption of intramolecular
      disulfide bonds affects the transport of PSA from the endoplasmic reticulum to
      the Golgi apparatus. The biosynthesis of PSA is potentiated by testosterone and
      inhibited by brefeldin A and DTT. These results will help us understand PSA
      biosynthesis and secretion in human prostate cancers.

PMID- 9288796
TI  - Melanoma cell-cell interactions are mediated through heterophilic Mel-CAM/ligand
      adhesion.
AB  - Mel-cell adhesion molecule (CAM), also known as MUC18 and CD146, is a novel
      member of the immunoglobulin supergene family. Mel-CAM was first identified as an
      integral membrane glycoprotein in human melanoma and is also abundantly expressed
      by endothelial cells of various origins. In a previous study (I. M. Shih et al.,
      Cancer Res., 54: 2514-2520, 1994), we showed that Mel-CAM is a cell-cell adhesion
      molecule with a possible role in melanoma invasion and metastasis. Here, we
      define the molecular mechanism responsible for cell-cell adhesion of Mel-CAM and
      demonstrate its role in melanoma-endothelial cell interactions. Most of human
      melanoma cells, including Mel-CAM-negative SBcl-2 cells, adhered to
      nitrocellulose-immobilized Mel-CAM produced by baculovirus recombinants. This
      adhesion can be blocked by full-length Mel-CAM or polyclonal antiserum against
      Mel-CAM. Adhesion is not affected by the presence of EDTA, truncated Mel-CAM
      extracellular domain, or heparan sulfate proteoglycan. In cell aggregation
      assays, Mel-CAM-negative SBcl-2 cells cluster with U937TM cells (U937 transfected
      with Mel-CAM cDNA) but not with control nontransfectants, suggesting that SBcl-2
      cells express the ligand for Mel-CAM. SBcl-2 cells also form heterotypic
      aggregates with Mel-CAM-positive human endothelial cells but not with Mel-CAM
      negative but ligand-positive smooth muscle cells. Taken together, our results
      show that Mel-CAM mediates cell-cell adhesion through heterophilic adhesion to an
      as yet unidentified ligand present on melanoma but not on endothelial cells.
      Thus, melanoma-endothelial interactions during metastasis may occur through this
      novel mechanism.

PMID- 9288797
TI  - Simultaneous detection of all four alkaline phosphatase isoenzymes in human germ
      cell tumors using reverse transcription-PCR.
AB  - We have developed a reverse transcription-PCR method that clearly distinguishes
      between the RNA transcripts of all four alkaline phosphatase (AP) genes. If
      compared to the methods used up to the present, the main advantages of the
      reverse transcription-PCR method presented are its specificity and high
      sensitivity. The germ cell AP and the placental AP, which are the two most
      closely related AP isoenzymes (98% homology), can clearly be distinguished
      without any interference by other AP isoenzymes. An enhanced expression of AP
      isoenzymes has been reported for various tumors. The examination of the pattern
      of AP isoenzyme expression in a specific tumor and the corresponding tissue of
      origin enables discrimination between eutopically and ectopically expressed
      isoenzymes and thus represents an important tool in the elucidation of AP
      isoenzymes as potential tumor markers. The pattern of AP expression in 15 germ
      cell tumors, 2 germinal epithelia adjacent to seminoma, 2 cell lines of germ cell
      tumor origin (Tera-1 and BeWo), and 5 normal testes was studied. In comparison to
      normal testes, in all seminomatous germ cell tumors eutopic expression of germ
      cell AP and ectopic expression of tissue-nonspecific AP were demonstrated. In
      both samples of pure embryonal carcinoma and in the embryonal carcinoma cell
      line, the transcription of all four mRNAs was shown. These results indicate that
      the expression of the isoenzymes depends on the degree of differentiation of a
      tumor and that a simultaneous up-regulation of all AP isoenzymes in all types of
      germ cell tumors does not exist.

PMID- 9288798
TI  - A highly sensitive model for quantification of in vivo tumor angiogenesis induced
      by alginate-encapsulated tumor cells.
AB  - A remarkable approach to a specific tumor angiogenesis model in vivo is the use
      of alginate implants encapsulating tumor cells. However, this previously reported
      approach has often been questioned because of doubts regarding the relevance of
      hemoglobin at the alginate implant as a parameter of vascularization. In the
      present investigation, we examined whether or not the use of the blood pool
      agents FITC-dextran of high molecular weight would significantly improve the
      determination of vascularization at the alginate implant. In our experiments, we
      found a rapid distribution of FITC-dextran within the blood circulation of mice
      after i.v. bolus injection. The amount of FITC-dextran within alginate implants
      strongly correlated with the number of LL2 carcinoma cells or B16/F10 cells
      encapsulated. Even a low number of 10(3) cells per alginate implant led to a
      significantly increased accumulation of FITC-dextran. A more than 10-fold
      stimulation above that of controls was found with alginate implants containing
      10(4) LL2 or B16/F10 tumor cells. Using the investigational compound AGM-1470 in
      different treatment schedules, we found that quantification of alginate implant
      anglogenesis with FITC-dextran is a sensitive method for the determination of
      angiogenesis inhibition. In conclusion, our results demonstrated that the use of
      FITC-dextran enables highly sensitive, quantitative measurement of blood vessel
      formation by alginate implants.

PMID- 9288799
TI  - Up-regulation of flk-1/vascular endothelial growth factor receptor 2 by its
      ligand in a cerebral slice culture system.
AB  - Vascular endothelial growth factor (VEGF) and its tyrosine kinase receptors VEGFR
      1 (flt-1) and VEGFR-2 (flk-1/KDR) are key mediators of physiological and
      pathological angiogenesis. They are expressed in most tissues during embryonic
      development but are down-regulated in the adult, when angiogenesis ceases. Up
      regulation of VEGFR-2 and of VEGF are observed in many pathological conditions
      under which angiogenesis is reinduced. A major regulator of VEGF expression is
      hypoxia. Although the temporal expression pattern of VEGFR-2 parallels VEGF
      expression to a high extent, little is known about its regulation. Here, we show
      that VEGFR-2 is highly expressed in early postnatal mouse brain but is down
      regulated commencing at postnatal day 15 (P15) of mouse brain development and is
      hardly detectable in P30 mouse brain. Using P30 mouse brain slices, we observed
      that hypoxia up-regulates VEGFR-2 in the slices but not in human umbilical vein
      endothelial cells, suggesting the presence of a hypoxia-inducible factor in the
      murine neuroectoderm that up-regulates VEGFR-2. To identify the factors involved,
      normoxic P30 cerebral slices were cultured with growth factors that are either
      hypoxia-inducible (e.g., PDGF-BB, erythropoietin, and VEGF) and/or are known to
      act on endothelial cells (e.g., PDGF-BB, VEGF, and PIGF). Exogenously added
      recombinant VEGF led to an up-regulation of VEGFR-2 expression, which could be
      inhibited by preincubation with a neutralizing anti-VEGF antibody. Addition of
      PDGF-BB, PIGF, and erythropoietin had no effect on VEGFR-2 expression. Our
      results suggest a differential but synergistic regulation by hypoxia of VEGF and
      VEGFR-2: a direct induction of VEGF that subsequently up-regulates VEGFR-2 in
      endothelial cells. This autoenhancing system may represent an important mechanism
      of tumor angiogenesis.

PMID- 9288801
TI  - Impact of dengue virus infection on feeding behavior of Aedes aegypti.
AB  - In addition to heavily infecting the salivary glands of Aedes aegypti (L.)
      mosquitoes, dengue viruses produce a significant infection of the nervous system,
      involving the brain, Johnston's organ, compound eye, and thoracic and abdominal
      ganglion. To determine if dengue infection affects feeding behavior of Ae.
      aegypti we measured feeding times, counted the number of feeding delays or
      interruptions, and by in situ immunocytochemistry techniques determined the
      spatial and temporal distribution of dengue infections in females parenterally
      infected with dengue 3 virus. The mean of the total time required for feeding by
      infected mosquitoes was significantly longer than the time required by uninfected
      mosquitoes. Similarly, the mean of the time spent probing was significantly
      longer in infected mosquitoes than in uninfected mosquitoes when day after
      inoculation was considered. Significant increases in the length of feeding
      activity in infected mosquitoes corresponded to virus infection in organs that
      are known to control or influence activities associated with blood feeding.
      Sequential infections of the salivary glands (five days postinoculation [PI]),
      brain and compound eye (eight days PI), and Johnston's organ and midgut and
      abdominal ganglion (11 days PI) of most mosquitoes were observed. The increased
      time required by infected Ae. aegypti mosquitoes to acquire a blood meal may
      contribute to the efficiency of Ae. aegypti as a vector of dengue virus. Longer
      feeding periods are more likely to be interrupted by the host, which increases
      the chance that an infected mosquito will probe or feed on additional hosts.

PMID- 9288802
TI  - Venereal and vertical transmission of the Aedes albopictus parvovirus in Aedes
      aegypti mosquitoes.
AB  - Following per oral infection of Aedes aegypti larvae with Aedes albopictus
      parvovirus (AaPV), infected males and females adults were tested for their
      ability to transmit the virus venereally and vertically, respectively. Both types
      of transmission were observed. A low percentage (2.2%) of AaPV-free females were
      found contaminated by the virus after mating with AaPV-infected males. Although
      no significant difference was observed in the fecundity of orally infected and
      virus-free females, 17.1% of infected ones died before egg laying, whereas no
      mortality occurred during the same period in virus-free females. There was a
      clear relationship between the virus titer in the orally infected females and
      both mortality and infection in their offspring. The virus titer averaged 10(6.2)
      50% tissue culture infective doses (TCID50s) in F1 females and 10(3.3) TCID50 in
      F1 females. Nevertheless, AaPV did not persist in an experimentally infected
      population of mosquitoes beyond the second generation.

PMID- 9288800
TI  - Up-regulation of vascular endothelial growth factor expression in a rat glioma is
      conferred by two distinct hypoxia-driven mechanisms.
AB  - Up-regulation of vascular endothelial growth factor (VEGF) expression is a major
      event leading to neovascularization in malignant gliomas. Hypoxia is believed to
      be the crucial environmental stimulus for this up-regulation. To critically
      assess this hypothesis, we asked whether the mechanisms defined previously for
      hypoxia-induced VEGF expression in vitro are similarly involved and sufficient
      for up-regulation of VEGF gene expression in vivo, using a lacZ reporter gene
      under the control of VEGF regulatory sequences in an experimental glioma model.
      Inclusion of the binding site for hypoxia-inducible factor 1 (HIF 1) in the 5'
      regulatory sequences used in the hybrid gene produced weak beta-galactosidase
      staining in a special tumor cell subtype, the so-called perinecrotic palisading
      (PNP) cells that flank necrotic regions within the tumor. Deletion of the HIF 1
      binding site abolished reporter gene expression in the PNP cells, indicating that
      transcriptional activation of VEGF expression in gliomas is mediated by HIF 1.
      Inclusion of 3' untranslated sequences from the VEGF gene in the reporter
      constructs resulted in an increased beta-galactosidase staining in the PNP cells,
      suggesting that mRNA stabilization also contributes to VEGF up-regulation in
      glioblastoma cells growing as solid tumors. Combination of the 5' flanking region
      including the HIF 1 site along with 3' untranslated sequences produced increased
      levels of beta-galactosidase expression in PNP cells. EF 5 immunostaining for
      regions of low oxygen partial pressure covered the same PNP cells that were
      stained for beta-galactosidase. Collectively, the data provide experimental
      evidence that VEGF gene expression is activated in a distinct tumor cell
      subpopulation, the perinecrotic palisading cells of gliomas, by two distinct
      hypoxia-driven regulatory mechanisms.

PMID- 9288803
TI  - An epidemic of sylvatic yellow fever in the southeast region of Maranhao State,
      Brazil, 1993-1994: epidemiologic and entomologic findings.
AB  - Yellow fever virus transmission was very active in Maranhao State in Brazil in
      1993 and 1994. An investigation was carried out to evaluate the magnitude of the
      epidemic. In 1993, a total of 932 people was examined for yellow fever from
      Maranhao: 70 were positive serologically, histopathologically, and/or by virus
      isolation, and another four cases were diagnosed clinically and
      epidemiologically. In Mirador (17,565 inhabitants), the incidence was 3.5 per
      1,000 people (case fatality rate [number of deaths/number of cases diagnosed] =
      16.4%), while in a rural yellow fever risk area (14,659 inhabitants), the
      incidence was 4.2 and the case-fatality rate was 16.1% (10 of 62). A total of
      45.2% (28 of 62) asymptomatic infections were registered. In 1994, 49 serum
      samples were obtained and 16 cases were confirmed (two by virus isolation, two by
      seroconversion, and 12 by serology). No fatal cases were reported. In 1993, 936
      potential yellow fever vectors were captured in Mirador and a single strain was
      isolated from a pool of Haemagogus janthinomys (infection rate = 0.16%). In 1994,
      16 strains were isolated from 1,318 Hg. janthinomys (infection rate = 1.34%) and
      one Sabethes chloropterus (infection rate = 1.67%). Our results suggest that this
      was the most extensive outbreak of yellow fever in the last 20 years in Brazil.
      It is also clear that the lack of vaccination was the principal reason for the
      epidemic, which occurred between April and June, during the rainy season, a
      period in which the mosquito population in the forest increases.

PMID- 9288804
TI  - Association of infections with human immunodeficiency virus and human
      papillomavirus in Honduras.
AB  - The etiologic role of the oncogenic types of human papillomavirus (HPV) in the
      development of cervical cancer has been widely proven. Since this cancer occurs
      more frequently in immunosuppressed individuals, we sought to evaluate the
      prevalence of HPV infection among human immunodeficiency virus (HIV)-infected and
      HIV-noninfected prostitutes in Tegucigalpa, Honduras. Cervical scrapes were
      collected from 23 HIV-seropositive and 28 HIV-seronegative prostitutes for HPV
      DNA detection by the polymerase chain reaction. Fifty-six percent of the HIV
      seropositive women and only 18% of the seronegative women were HPV DNA positive
      (odds ratio = 6.0). In addition, there was a significant association between
      seropositivity for HIV with a history of sexually transmitted diseases (P <
      0.01). Our data confirm the association between infections with HIV and HPV.

PMID- 9288805
TI  - Laboratory characterization of human T cell lymphotropic virus types 1 (HTLV-1)
      and 2 (HTLV-2) infections in blood donors from Sao Paulo, Brazil.
AB  - Serologic screening for human T cell lymphotropic virus types 1/2 (HTLV-1/2)
      infection in blood donors has been recently introduced in Brazil. Analysis of
      351,639 blood donations in Sao Paulo from January 1992 to October 1993 identified
      1,063 positive (0.30%) and 2,238 indeterminate (0.63%) samples based on serologic
      confirmation using a 21e Western blot. A detailed analysis (serologic, molecular,
      and virologic), based on a laboratory diagnostic algorithm for characterization
      of HTLV-1 and HTLV-2 infections was undertaken in 50 seropositive or
      seroindeterminate blood donors. Modified serologic assays (2.3 Western blot that
      incorporate type-specific recombinant peptides) performed in 29 HTLV-1/2 positive
      and 21 HTLV-1/2 indeterminate donors with the 21e Western blot identified 25 as
      infected with HTLV-1, four with HTLV-2, five with untypable HTLV-1/2, 15 as HTLV
      1/2 indeterminate, and one as seronegative. Polymerase chain reaction (PCR)
      analysis using DNA amplification of proviral pol and tax sequences from
      peripheral blood mononuclear cells confirmed HTLV-1 and HTLV-2 infections in all
      2.3 Western blot seropositive donors; of the five serologically untypable donors,
      three were confirmed to be HTLV-1 positive, one HTLV-2 positive, and one negative
      by PCR. All of the seroindeterminate donors were also negative by PCR.
      Furthermore, HTLV-1 could be isolated in cocultures from 10 of 18 infected
      donors. Cell lines developed from two HTLV-1-infected donors were of T cell
      phenotype (CD2+, CD3+), exhibiting surface markers of activated CD4 cells (CD4+
      CD25+ HLA-DR+). Thus, we provide evidence for the high seroprevalence of HTLV
      infection in blood donor population in Sao Paulo, Brazil compared with North
      American donors and propose a comprehensive serologic and genotypic diagnostic
      algorithm for HTLV-infected donors that has strong implications for counseling of
      these individuals.

PMID- 9288806
TI  - Short report: further evidence for hepatitis E in the Brazilian Amazon.
AB  - During an investigation of a hepatitis outbreak occurring in a small village in
      the Brazilian Amazon, serum samples from 16 recent hepatitis cases and 66 of
      their asymptomatic relatives were tested for the presence of hepatitis A, B, C,
      and E markers. Sanitation is poor and organized disposal of sewage is absent in
      the village. Two of the 16 hepatitis cases were non-A, non-B and non-C hepatitis,
      but their sera reacted to hepatitis E antibodies of the IgG class (anti-HEV).
      Likewise, sera from seven of the 66 asymptomatic relatives were positive for anti
      HEV. Four of the nine anti-HEV positive sera had their reactivity confirmed by a
      neutralization test using synthetic peptides based on the nucleotide sequences of
      open reading frames 2 (ORF2) and 3 (ORF3) encoded in the HEV genome. To our
      knowledge, this is the first report suggesting the occurrence of acute E
      hepatitis cases in the Brazilian Amazon.

PMID- 9288807
TI  - Water-borne hepatitis E virus epidemic in Islamabad, Pakistan: a common source
      outbreak traced to the malfunction of a modern water treatment plant.
AB  - During December 1993 and in the first three months of 1994, an explosive water
      borne epidemic of hepatitis E virus (HEV) occurred in two sectors of Islamabad,
      Pakistan. In a survey of a population of 36,705 individuals, a total of 3,827
      cases of acute icteric hepatitis were recorded with an overall attack rate (AR)
      of 10.4%. The etiologic role of HEV in the epidemic was proven by demonstrating
      anti-HEV IgG and HEV IgM in the tested serum samples. The water-borne nature of
      the epidemic was suggested by a study of the case distribution according to water
      supply. Prior to the epidemic, there had been an operational breakdown in a water
      treatment plant that distributed water to the affected areas while transforming
      its purification system from slow sand to rapid sand filtration. The primary
      source of water for the plant was derived from a heavily contaminated stream. The
      highest AR (16.3%) was observed in the areas where the source of drinking water
      was exclusively from the purification plant, followed by ARs of 12.4% and 5.3%
      for those receiving 50% and 30% or less of their water supply from the treatment
      plant, respectively, while the lowest AR (1.8%) was observed in the neighboring
      areas that did not receive water from this source. The AR was significantly
      higher in the group 11-30 years of age (15.3%) as compared with children less
      than 11 years of age (1.4%) and also relative to the group greater than 30 years
      of age (10.5%). The AR among the 162 recorded pregnant females was 21.6%, which
      was higher than that found among nonpregnant females of child-bearing age
      (10.9%). All four reported adult deaths occurred among females in their third
      trimester of pregnancy with a case fatality rate of 11.4%, while the other four
      fatal cases were newborn infants of mothers with acute icteric hepatitis.
      Although the aggregation of cases within households was significantly related to
      family size, the temporal relationship between cases in households with two or
      more cases revealed that 83.7% of 1,463 presumed secondary cases occurred within
      one month of the first case in the same household, which is not suggestive of
      person-to-person transmission of disease. The termination of providing water from
      the source was effected, which was followed by an apparent decrease in cases.

PMID- 9288808
TI  - Urinary schistosomiasis contracted from an irrigation pool in Ramah, the southern
      Jordan Valley, Jordan.
AB  - Autochthonous cases of urinary schistosomiasis are reported for the second time
      in Jordan. Eight Jordanian juveniles (seven males and one female) ranging in age
      from 10 to 15 years were diagnosed in 1995 as having the disease. Urine
      examination using the membrane filtration technique showed varying intensities of
      infection. The patients were treated with praziquantel and a follow-up showed the
      passage of dead eggs in the urine of five patients one month after treatment. All
      had egg-negative urine three months post-treatment. Epidemiologic investigation
      showed that the patients did not leave Jordan and that the seven males swam
      frequently in 1994 in an irrigation pool present in a farm at Ramah, in the
      southern Jordan Valley. The female patient had frequent contact with the pool
      water since she often went to the farm to obtain water for domestic animals.
      Bulinus truncatus snails were found in the pool and in pools on other farms in
      the area. Two hundred snails collected from the site did not shed cercariae after
      six months of observation. Several foreign workers in the area were found
      infected with Schistosoma haematobium, suggesting they were the source of
      infection.

PMID- 9288809
TI  - Cercarial density in the river of an endemic area of schistosomiasis haematobia
      in Kenya.
AB  - The cercarial density in natural water and number of infected Bulinus globosus
      were monitored over a one-year period to identify the transmission foci in an
      endemic area of schistosomiasis haematobia in Kenya. Overall prevalence and
      intensity of infection of the study community were 59.2% and 10.9 eggs/10 ml of
      urine. Cercariometry was carried out on 456 occasions at 20 study sites while
      snail sampling was done on 465 occasions at the same sites over a one-year
      period. Cercariometry was exclusively done at flowing water habitats. The results
      showed the focality and seasonality of transmission. Cercariae were detected on
      44 occasions at 11 sites. The detections were made on seven occasions at two
      study sites, six occasions at one site, four occasions at four sites, three
      occasions at one site, two occasions at two sites, and one occasion at one site.
      Densities of 1-4 cercariae/100 liters of water were found on 31 occasions. Five
      to nine cercariae/100 liters of water were found on seven occasions, 10-19
      cercariae/100 liters of water were found on two occasions, and high cercarial
      densities greater than 20 cercariae/100 liters of water were found on four
      occasions. The highest count was 52 cercariae/100 liters of water. The presence
      of cercariae in natural water was shown to depend on the water temperature, but
      the intensity and duration of sunlight did not affect the presence of cercariae
      in water. The monthly variability of cercarial density was proportional to the
      number of infected snails. Cercarial density was highest in March and April, in
      the middle of the rainy season, whereas no cercariae were detected in cool dry
      season. The snail population peaked late in March, the beginning of the long
      rainy season, remained high for two months, and decreased rapidly late in May
      when heavy rain occurred. The overall infection rate of snails was 7.3% and the
      majority of infected snails were collected from March to May. There was no
      definite correlation between the presence or absence of cercariae and infected
      snails. Cercariae were frequently found where infected snails were absent and
      cercariae were sometimes absent where infected snails were present. Cercariometry
      and snail sampling remain quite complementary in identifying the transmission
      foci of schistosomiasis.

PMID- 9288810
TI  - Prevalence of anti-Leishmania donovani antibody among Brazilian blood donors and
      multiply transfused hemodialysis patients.
AB  - The prevalence of anti-Leishmania donovani antibodies was investigated in 1,500
      Brazilian blood donors and multiply transfused hemodialysis patients. Sera were
      tested using the fucose-mannose ligand (FML) ELISA, which was shown to have 100%
      sensitivity and 96% specificity for kala-azar. Among 1,194 volunteer blood
      donors, seroreactivity was 9%, increasing to 25% in a periurban kala-azar focus.
      However, higher positivity (37%) was found in multiply transfused hemodialysis
      patients from Natal, where kala-azar is constantly present in low numbers
      (endemic), with sporadic outbreaks in localized regions (endemic and epidemic).
      Risk factors included blood transfusion, which was significantly associated with
      the presence of anti-Leishmania antibodies (chi2 = 8.567, P < 0.005), but did not
      include potential exposure to sandfly bites (chi2 = 0.033, P > 0.1). The
      prevalence significantly decreased to 7% in hemodialysis patients from Rio de
      Janeiro, where kala-azar is only occasionally seen, and was 0% in patients
      undergoing continuous ambulatorial peritoneal dialysis. The prospective analysis
      of 27 FML-seroreactive donors from Natal revealed amastigotes of Leishmania in
      the bone marrow of one subject while four had clinical complaints, including
      splenomegaly and hepatosplenomegaly. Our results point to the need for control of
      blood transfusion as a possible route for transmission of kala-azar in endemic
      areas.

PMID- 9288811
TI  - Short report: Leishmania tropica: etiologic agent of a case of canine visceral
      leishmaniasis in northern Morocco.
AB  - The domestic dog has been previously demonstrated to be the reservoir of
      Leishmania infantum, the etiologic agent of human visceral leishmaniasis around
      the Mediterranean Basin. It can also be infected with L. tropica, the etiologic
      agent of anthroponotic cutaneous leishmaniasis in Morocco. We report a canine L.
      tropica visceral infection for the first time in Morocco.

PMID- 9288812
TI  - Bartonellosis in Ecuador: serosurvey and current status of cutaneous verrucous
      disease.
AB  - Human bartonellosis is a classically biphasic disease caused by infection with
      the alpha-2 Proteobacteria Bartonella bacilliformis, which is phylogenetically
      related to the etiologic agents of cat scratch disease, bacillary angiomatosis,
      and trench fever. In Ecuador, typical bartonellosis has remained endemic for the
      past century in highland provinces near the Peruvian border. During the past six
      years, public health officials have noted an increasing number of atypical cases
      in which monophasic verrucous cutaneous disease is the only clinical
      manifestation. Epidemiologic, immunologic, histopathologic, and molecular
      biological studies have confirmed the presence of sporadic, atypical
      bartonellosis in residents of the lowland province of Manabi, where archeologic
      evidence exists of bartonellosis in pre-Colombian times. Between 1987 and 1995,
      11 cases of cutaneous bartonellosis were investigated and serologic studies were
      done on 224 persons from five villages, two lowland and three highland. In the
      lowland village of Pajan in the province of Manabi, there was a 21%
      seropositivity proportion in contacts of index cases. These combined data suggest
      that bartonellosis is significantly under-reported due to the existence of mild
      clinical disease, possibly associated with less virulent bacterial strains, which
      are now disseminating or re-emerging in previously disease-free areas.

PMID- 9288813
TI  - A maternal screening program for congenital toxoplasmosis in Quindio, Colombia
      and application of mathematical models to estimate incidences using age
      stratified data.
AB  - We studied 937 pregnant women from Quindio, Colombia for the presence of specific
      anti-Toxoplasma gondii IgG antibodies using the indirect immunofluorescence
      antibody technique (IFAT-IgG). Specific anti-T. gondii IgM antibodies detected
      using the immunosorbent agglutination assay (ISAgA-IgM) were investigated in
      patients with high titers in the IFAT-IgG (dilutions > or = 1:1,024). We used
      mathematical models based on the age prevalence results of the IFAT-IgG to
      estimate the number of seroconversions and these were compared with the results
      predicted by the IgM based-incidence results. We found 15 positive cases by ISAgA
      IgM and we were able to follow the children of six mothers from this group in
      which we found one case of congenital toxoplasmosis with the development of a
      retinal scar despite prenatal and postnatal treatment. The estimation of new
      cases for the annual total of pregnancies (approximately 8,000) in the Quindio
      region was 30-120 according to the ISAgA-IgM results and 57-85 using mathematical
      models. Thus, mathematical models based on age prevalence can give useful
      estimations of the magnitude of the problem.

PMID- 9288815
TI  - Skin test and radioallergosorbent test characteristics of scabietic patients.
AB  - The scabies mite Sarcoptes scabiei and the Dermatophagoides house dust mites
      (HDM) are related phylogenetically and are the sources of several cross-reactive
      antigens. The purpose of this study was to investigate the immune response to S.
      scabiei and HDM in scabietic patients. Skin test sensitivity and serum IgE to
      both S. scabiei and HDM were determined for patients who had or previously had
      confirmed ordinary scabies. A retrospective group included nine subjects who had
      received successful treatment three weeks to one year prior to the study. A
      prospective group included 16 subjects with active scabies. Allergic histories
      were obtained, serum was collected, and skin prick tests (SPTs) were performed at
      enrollment for all and periodically over the next 12 months for the prospective
      patients. None of the individuals in either group reported a known sensitivity to
      HDM. Six of the nine retrospective patients were SPT positive to both S. scabiei
      and HDM and two of these showed circulating IgE specific for these antigens. At
      diagnosis, 13 of 16 patients with active scabies were SPT positive to S. scabiei
      and 12 of these were also SPT and/or radioallergosorbent test positive to HDM.
      Six patients had circulating IgE directed at both S. scabiei and HDM antigens
      while one subject had IgE to S. scabiei only and another had IgE directed at HDM
      only. Twelve of the 15 subjects tested also showed IgE and/or IgG binding to one
      or more bands on Western blots of an S. scabiei-specific protein fraction. This
      study indicated that approximately half of the patients with active scabies had
      S. scabiei- and HDM-specific circulating IgE while most patients cured of scabies
      lacked S. scabiei- and HDM-specific serum IgE. The data also suggested that
      antibodies to S. scabiei in scabietic patients also recognize HDM; however, some
      antibodies were directed at scabies-specific antigens.

PMID- 9288814
TI  - Seroepidemiology of Rickettsia typhi, spotted fever group rickettsiae, and
      Coxiella burnetti infection in pregnant women from urban Tanzania.
AB  - Immunofluorescent antibody (IFA) testing was performed on sera drawn from 150
      pregnant women in the port city of Dar es Salaam, Tanzania. Prevalence of
      antibodies to Rickettsia typhi was 28%, higher than in any of the 12 other
      African countries in which serosurveys using IFA testing have been performed.
      Seroprevalence of antibodies to spotted fever group rickettsiae antigens was
      25.3%, comparable with that found in other sub-Saharan countries endemic for
      Amblyomma ticks. Only 4.7% of women were seropositive for Coxiella burnetii.

PMID- 9288817
TI  - Detection of microfilarial antigen in circulating immune complex from sera of
      Wuchereria bancrofti-infected individuals.
AB  - Polyethylene glycol-precipitated circulating immune complexes (CICs) from the
      sera of patients with Bancroftian filariasis were examined for parasite antigen
      content by an ELISA. Of the 227 patients, 214 were asymptomatic microfilariae
      carriers with microfilaremias ranging between six and 14,000/ml blood, and 13
      were symptomatic patients with chronic filariasis without microfilaremia. In
      addition, the sera of 10 of the patients treated with diethyl carbamazine were
      also examined. These assays were devised using mouse monoclonal antibody raised
      against microfilariae of Wuchereria bancrofti. Using an acid-phase covalent-bound
      plate for the ELISA makes it possible to assay the antigen contents simply.
      Microfilarial antigens were detected from 92 (43.0%) of microfilaria (mf)
      positive individuals. Furthermore, the level of antigen in CIC was correlated
      with mf counts from night blood Nuclepore filtration results. Antigen was not
      detected in CIC from patients with a variety of nonfilarial helminth infections.
      These findings indicate that microfilariae play an important role of CIC
      formation in lymphatic filariasis.

PMID- 9288816
TI  - Immunogenicity of recombinant hepatitis B vaccine among infants of mothers with
      active schistosomiasis.
AB  - A study of the immunogenicity of a recombinant hepatitis B vaccine was conducted
      among 385 Egyptian infants, 191 (49.6%) of whom were born to mothers with
      moderately active Schistosoma mansoni infection (mean egg count = 224 eggs/g of
      feces). All mothers were seronegative for hepatitis B surface antigen (HBsAg) and
      hepatitis B e antigen. Infants were vaccinated with a 2.5-microg dose of this
      vaccine, given along with diphtheria, tetanus, and pertussis (DTP) vaccine, at
      the ages of two, four, and six months. Serum samples taken from each infant at
      nine months of age were tested for HBsAg, antibody to hepatitis B core antigen,
      and quantitatively for antibody to hepatitis B surface antigen (anti-HBs). There
      was no significant difference (P = 0.1) between anti-HBs titers in infants of S.
      mansoni-infected mothers (mean = 539 mIU/ml) and in infants of noninfected
      mothers (mean = 377 mIU/ml). This study shows that there was no apparent effect
      of maternal schistosomiasis infection on the immune response of these infants to
      vaccination.

PMID- 9288818
TI  - Limited spatial clustering of individual Plasmodium falciparum alleles in field
      isolates from coastal Kenya.
AB  - We describe Plasmodium falciparum genetic diversity in coastal Kenya, typing S
      antigen and the merozoite surface proteins 1 and 2 (MSP-1 and MSP-2) in field
      isolates by the polymerase chain reaction (PCR). Malaria in coastal Kenya is
      characterized by low seasonal transmission, and a relatively high incidence of
      severe disease, which tends to occur in time-space clusters. We chose the highly
      polymorphic S-antigen as a marker for localized parasite diversity because it has
      been shown to vary in serotype prevalence in time and space. A total of 261
      children (up to nine years of age) in two neighboring locations with different
      transmission rates were sampled for blood-stage parasites in cross-sectional
      surveys before and after the main transmission period in 1991, and also in a
      concomitant one-year longitudinal survey tracing clinical infections. Six major
      sequence types of S-antigen were identified, which were subdivided into 70
      alleles; however, only 50% of isolates were typeable. The S-antigen sequence
      types varied qualitatively between locations, over time, and between asymptomatic
      and clinical disease infections, but not between different age groups. The MSP-1
      and MSP-2 sequence type prevalences, in contrast, did not differ in any of these
      comparisons. We describe the use of the Mantel test for assessing clustering of
      individual parasite alleles at the household level, and demonstrate low-level
      clustering of MSP-1 and MSP-2 alleles and S-antigen sequence types, at the end of
      a long period of low transmission.

PMID- 9288819
TI  - Patterns of genetic variability in colonized strains of Lutzomyia longipalpis
      (Diptera: Psychodidae) and its consequences.
AB  - The genetic qualities of laboratory colonies of phlebotomine sand flies have not
      been compared with field specimens despite 1) probable genetic shifts due to the
      colonization process and 2) the problems associated with the extrapolation of
      experimental data derived from colonized organisms to field populations. The
      present study compared the genetic profiles of five laboratory colonies of
      geographic strains of the New World sand fly Lutzomyia longipalpis, and
      contrasted them with field populations. The profiles were based on the
      variability exhibited with polyacrylamide gels at 14 enzyme loci. A general
      pattern of a loss of infrequent alleles and decreased heterozygosity emerged as
      an apparent consequence of colonization. The average number of alleles per locus
      ranged from 1.2 to 1.6, and the average heterozygosity ranged from 4% to 11%. The
      field collection from Lapinha Caves (near Belo Horizonte, Brazil) averaged 2.1
      alleles with a heterozygosity of 16%. In contrast, the LAPINHA laboratory colony
      established from that site 24 years earlier showed very low values (1.2
      alleles/locus and 4% heterozygosity) and fixation for alleles not present or rare
      in the field collection from the same site. The genetic differences between the
      other Brazilian colonies and the Lapinha Caves field samples were due to presence
      of both different alleles and highly diverged allelic frequencies. Biological
      inferences based on colonized sand flies must be tempered by recognizing that the
      colony may represent a highly skewed genetic subsample of the L. longipalpis
      field genome.

PMID- 9288820
TI  - Genotypic and phenotypic variation of selected Saint Louis encephalitis viral
      strains isolated in California.
AB  - The mechanism for long-term maintenance of St. Louis encephalitis (SLE) virus in
      California is unknown. Two possibilities are 1) that the virus is maintained
      locally in discrete enzootic foci by one or more reservoir mechanisms, and/or 2)
      that the foci are ephemeral in nature and virus is reintroduced periodically from
      other enzootic areas by migratory birds or movement of vectors. We have
      investigated these epidemiologic alternatives by studies of genetic variation
      within a 277 nucleotide portion of the envelope-encoding region among 17 strains
      of SLE virus isolated since 1952 from different geographic locations in
      California. Three lineages of virus were detected. One lineage, Group A,
      consisted of four SLE virus strains isolated in California since 1972 from the
      Coachella, Sacramento, and San Joaquin Valleys. The group A strains were closely
      related to strain MSI-7 of SLE virus isolated in Mississippi in 1975. The 13
      other strains formed the second and third lineages (Groups B1 and B2) that had
      geographically overlapping distributions. Group A (BFN 4585) and Group B2 (BFN
      4820) appeared to be sympatric in the Sacramento Valley in 1972. Strains from the
      San Joaquin Valley isolated prior to 1989 (Groups B1 and B2) differed markedly
      from a 1989 isolate from the same location, Kern 373 (Group A). These results
      suggest that virus introduction(s) led to changes in genotype, or alternatively
      that the enzootic virus was subjected to selective pressure leading to rapid
      emergence of a new genotype. Nucleotide sequences of the envelope and 5'
      untranslated region of the viral genome of these virus strains did not correlate
      with virulence as measured by mortality in weanling mice, nor viremia levels and
      duration in chickens.

PMID- 9288822
TI  - A fitness advantage for Aedes aegypti and the viruses it transmits when females
      feed only on human blood.
AB  - Literature on arthropod-borne diseases has traditionally supported the notion
      that mosquito vectors maintain a feeding duality that includes vertebrate blood
      meals for egg development and sugar meals from plants for the synthesis of flight
      and survival energy reserves. Aedes aegypti was found to deviate from that
      feeding pattern by obtaining a reproductive advantage when feeding only on human
      blood. Female mosquitoes fed human blood alone had a greater net replacement rate
      and intrinsic rate of growth during all phases of their reproductive life than
      conspecifics fed human blood plus sucrose. Feeding frequently on human hosts
      during each gonotrophic cycle is necessary to avoid death due to starvation and
      increases exponentially the spread of Ae. aegypti-borne disease. Our results help
      explain why Ae. aegypti is such an unusually efficient vector of human disease;
      frequent biting of humans results in a high reproductive rate for vectors as well
      as the viruses they transmit.

PMID- 9288821
TI  - Genetic stability among temporally and geographically diverse isolates of Barmah
      Forest virus.
AB  - An increase in the incidence of polyarthritis caused by Barmah Forest (BF) virus,
      and its recent emergence into Western Australia, prompted a study of the
      molecular epidemiology of this Australian mosquito-borne alphavirus. The
      nucleotide sequence of a 500-basepair region of the 3' end of the envelope (E2)
      gene of the prototype BF virus strain (BH2193) was compared with other members of
      the alphavirus genus, and to a panel of isolates of BF virus collected more for
      than 20 years from different geographic regions of Australia. The BF virus was
      shown to be genetically distinct from other members of the alphavirus genus. A
      high degree of sequence homology (98-100%) was found between the BF isolates,
      with no evidence of geographic or temporal divergence. This nucleotide
      homogeneity was similar to that observed with other Australian mosquito-borne
      viruses with avian vertebrate hosts, such as Sindbis, Murray Valley, and Kunjin
      viruses, but it contrasts to the heterogeneity reported for Ross River virus, an
      alphavirus with mammalian vertebrate hosts.

PMID- 9288823
TI  - Mouse and baby chicken virulence of enzootic strains of western equine
      encephalomyelitis virus from California.
AB  - Eight enzootic strains of western equine encephalomyelitis (WEE) virus isolated
      from Culex tarsalis or Aedes melanimon collected in several geographic areas of
      California were evaluated for their virulence in suckling mice, adult mice, and
      one-day-old baby chickens. The epidemic Fleming strain and the cloned B628(Cl 15)
      variant were used as virulent and avirulent control viruses, respectively, in
      adult mice. Enzootic strains of WEE virus were grouped into three phenotypes on
      the basis of their neurovirulent and neuroinvasive properties in adult mice.
      Three strains possessed high neurovirulence and were neuroinvasive; three strains
      had intermediate neurovirulence and lacked neuroinvasiveness; and two strains had
      low to nil neurovirulence and were non-neuroinvasive. In fact, five of the eight
      enzootic strains lacked neuroinvasiveness. Interestingly, highly virulent
      enzootic strains of WEE virus were isolated from Cx. tarsalis collected in the
      Sacramento Valley during 1994 and 1995 in the absence of identified human
      disease. The Fleming strain, the B628(Cl 15) variant, and four enzootic strains
      from the Sacramento Valley were virulent for baby chickens following subcutaneous
      inoculation. Thus, inoculation into baby chicks cannot discriminate between WEE
      viruses that are virulent and avirulent for adult mice.

PMID- 9288825
TI  - Behavioral validation of the elevated T-maze, a new animal model of anxiety.
AB  - The elevated T-maze test of anxiety has been used to separate in the same rat
      conditioned from unconditioned responses of fear/anxiety. The test apparatus
      consists of three elevated arms-one enclosed and two open. Inhibitory avoidance-
      representing learned fear--is measured by recording the time taken to leave the
      enclosed arm in three consecutive trials. Unconditioned fear is evaluated by
      recording the time to escape from the open arm. In this study we investigated
      procedural questions raised by the use of the elevated T-maze. Experiment 1
      showed that restraining the animals at the end of the enclosed arm for 30 s did
      not change the first (baseline) latency to leave this arm, indicating that
      aversion for the hands of the experimenter is not a key motivation for this
      response. The results of Experiment 2 indicated that open-arm experience, but not
      handling stress is the main cause for inhibitory avoidance acquisition, because
      rats trained in a T-maze with the three arms enclosed did not show the usual
      increase in withdrawal latency along the three consecutive trials. The same
      experiment also showed that the latency to leave the open arm did not undergo
      habituation over five consecutive trials, evidencing an aversive motivation for
      this response. The importance of open-arm experience for inhibitory avoidance
      acquisition was further suggested by the results of Experiment 3, as the removal
      of a shield that prevents perception of openness tended to increase avoidance
      latency in the elevated T-maze from the first trial.

PMID- 9288824
TI  - Organometric investigations of the spleen and liver by ultrasound in Schistosoma
      mansoni endemic and nonendemic villages in Senegal.
AB  - With the intention of ultrasonographically assessing hepatosplenic morbidity in
      Schistosoma mansoni infection and of validating the grading system applied (Cairo
      classification), 191 subjects in a schistosomiasis endemic village and 247
      controls from a nonendemic village in northern Senegal underwent sonographic
      examination of the liver and spleen. Measurements of the diameters of the
      peripheral periportal vein branches, the main portal vein stem, liver size (left
      lobe and right lobe), and spleen length in the endemic village were compared with
      those in the nonendemic village to evaluate the much discussed influence of S.
      mansoni infection on those variables. To subtract this presumed influence from
      reference values for the named variables, they are given as measured in the
      nonendemic village, stratified by body weight, enabling future investigators on
      schistosomiasis-induced morbidity to refer to these reference values. The 95th
      percentile regarding peripheral periportal vein branch diameter in the control
      groups was exceeded in 24% of the subjects in the endemic group. It was exceeded
      by 6% for the main portal vein stem diameter, 13% for the left liver lobe, 12%
      for the right liver lobe, and 14% for the spleen length. According to the Cairo
      classification, 97% of the endemic population and 81% of the controls had
      periportal thickening of the liver, mostly grade I. We conclude that 1) hepatic
      morbidity in the S. mansoni endemic area was low, despite strikingly high
      intensities of infection; 2) the Cairo classification in its present form
      overestimates periportal thickening, especially in the case of mild morbidity;
      and 3) body height-dependent reference values, obtained from endemic controls,
      must be applied for organometric parameters.

PMID- 9288826
TI  - Evaluation of simplified compartmental models of reconstructed neocortical
      neurons for use in large-scale simulations of biological neural networks.
AB  - The electrotonic properties of the complex arborizations of neurons can be
      simulated by creating compartmental models based on the morphology of real
      neurons. These models can be very detailed with thousands of individual
      compartments and active channels. Large numbers of these models can be linked
      together into biologically realistic, large-scale neural networks with which to
      obtain a better understanding of the interactions among real neurons. However,
      the use of detailed compartmental models in such large networks is hindered by
      long computation times. Methods exist to reduce the complex morphology of
      detailed compartmental models to simpler reconstructions that retain many of the
      electrotonic properties of the original model yet are computationally efficient.
      However, little work exists that evaluates the limitations and performance of
      such reduced models with realistic active conductances modeled in both the soma
      and the dendrites to ensure that they are appropriate for use in biologically
      realistic network models. We have created detailed and reduced models of
      reconstructed dye-filled neurons from rat somatosensory neocortex and evaluated
      the ability of the reduced models to faithfully reproduce the input-output
      functions of the more detailed models. We find that the reduced models are not
      capable of perfectly reproducing the exact output of the detailed models using
      identical parameters. However, if the parameters are adjusted the reduced models
      are certainly capable of providing input-output patterns that are well within an
      acceptable range of known neural activity. The limitations and the benefits of
      such models are discussed.

PMID- 9288827
TI  - Beta-endorphin inhibition of endogenous norepinephrine release from the A2
      noradrenergic nucleus in vitro: role of mu opiate receptors and Na+ ion
      permeability.
AB  - An in vitro approach was used to determine the opioid receptor subtype mediating
      beta-endorphin inhibition of endogenous norepinephrine release from the A2
      nucleus in the caudal dorsomedial medulla of rats. The voltage-sensitive Na+
      channel blocker tetrodotoxin was used to investigate the role of Na+-dependent
      action potentials in beta-endorphin inhibition of K+-evoked norepinephrine
      release. Human beta-endorphin(1-31) inhibited K+-evoked norepinephrine release in
      a concentration-dependent fashion. Activation of delta- and kappa-opioid
      receptors had no effect on endogenous norepinephrine release. The inhibitory
      effect of beta-endorphin was blocked in a concentration-dependent manner by the
      mu-opioid receptor antagonist CTOP (Cys2, Tyr3, Orn5, Pen7 amide). Tetrodotoxin
      (TTX) inhibited norepinephrine release evoked by 25 mM K+ in a concentration
      dependent manner and blocked the inhibitory effects of beta-endorphin. These
      results indicate that beta-endorphin acts on mu-opioid receptors to inhibit K+
      evoked norepinephrine release from A2 neurons and suggest that the receptors
      involved are not located on noradrenergic nerve terminals.

PMID- 9288828
TI  - Non-selectivity of the monoclonal antibody M35 for subtypes of muscarinic
      acetylcholine receptors.
AB  - The monoclonal antibody M35, one of the first monoclonal antibodies successfully
      raised against muscarinic acetylcholine receptors, has been widely used to study
      the distribution of this protein in a variety of tissues and cell types of
      different species. It is not fully known, however, to which muscarinic
      acetylcholine receptor subtypes M35 binds. Knowledge of subtype-selectivity of
      M35 is a necessary step towards a functional interpretation of the obtained
      immunocytochemical data. The aim of the present study was to determine the
      subtype-selectivity of M35 employing transfected CHO-K1 cells stably expressing
      human m1-m5 muscarinic acetylcholine receptors separately, and to study M35
      immunoreactivity in areas of rat central and peripheral tissues known to be
      specifically enriched in a single muscarinic acetylcholine receptor subtype. The
      results show that (a) all five transfected cell lines were immunopositive for
      M35, (b) nontransfected control cells were immunonegative, (c) the number of
      mAChRs expressed per cell correlated positively with the intensity of M35
      immunoreactivity, and (d) cell types in aldehyde-fixed rat tissue enriched in a
      single m1-m4 subtypes revealed clear M35 immunoreactivity. Taken together, the
      present results show that M35 does not discriminate between muscarinic
      acetylcholine receptor subtypes. Evidently, the epitope of M35 on the receptor
      protein is preserved on all muscarinic acetylcholine receptor subtypes. The
      epitope for M35 must, therefore, be localized on a homologous part of each
      subtype.

PMID- 9288829
TI  - Autoradiographic mapping of brain 5-HT2A binding sites in P and in AA alcohol
      preferring rats.
AB  - There is considerable evidence for an involvement of serotonergic mechanisms in
      the control of alcohol consumption. In the present study, an extensive 5-HT2A
      receptor autoradiographic investigation was carried out in two genetically
      selected rat strains, P and AA alcohol-preferring rats, respectively, as well as
      in the corresponding NP and ANA alcohol-nonpreferring rats. The aim was to
      determine if there is any common pattern in 5-HT2A binding site densities that
      may illuminate mechanisms of alcohol preference in these animals. For
      quantitating 5-HT2A binding sites, [3H]ketanserin (2 nM) was used. Nonspecific
      binding was measured in the presence of methysergide 10(-6) M. Results
      demonstrated a lower level (from 50 to 70%) of 5-HT2A binding sites in the layer
      IV of prefrontal cortex, frontal cortex, parietal cortex of P rats compared to NP
      controls. Similarly, in the claustrum, 5-HT2A binding density of P rats was 50%
      lower than that of NP rats, although this failed to achieve statistical
      significance. No difference was detected in the other areas investigated,
      including the olfactory tubercles, nucleus accumbens, caudate putamen, pyriform
      cortex, ventral tegmental area, temporal cortex, and entorhinal cortex. In AA
      rats, [3H]ketanserin binding density measured in these brain areas was very
      similar to that observed in ANA nonpreferring controls, and statistical analysis
      did not reveal any significant difference between the two rat lines. The present
      study confirms previous reports demonstrating lower densities of 5-HT2A binding
      sites in the P rats and provides the first autoradiographic evidence showing that
      such an alteration does not occur in AA rats. These findings suggest that the
      expression of high alcohol preference in genetically selected P and AA rats is
      not associated with a shared neurochemical alteration of the 5-HT2A receptor
      system.

PMID- 9288830
TI  - In vitro autoradiographic localization of 5-HT1A receptor-activated G-proteins in
      the rat brain.
AB  - Serotonin 5-HT1A receptors belong to the superfamily of G-protein-coupled
      receptors. Receptor activation of G-proteins can be determined by agonist
      stimulated [35S]GTPgammaS binding in the presence of excess GDP, and in vitro
      autoradiographic adaptation of this technique allows visualization of receptor
      activated G-proteins in tissue sections. The present study was performed to
      examine 5-HT1A receptor activation of G-proteins using 8-OH-DPAT-stimulated
      [35S]GTPgammaS binding in membranes and brain sections. In hippocampal membranes,
      8-OH-DPAT stimulated [35S]GTPgammaS binding by twofold, with an ED50 value of 25
      nM. 5-HT1 antagonists, but not 5-HT2 antagonists, increased the ED50 of 8-OH-DPAT
      in a manner consistent with competitive antagonists. Scatchard analysis of
      [35S]GTPgammaS binding showed that 8-OH-DPAT induced the formation of high
      affinity [35S]GTPgammaS binding sites with a KD for GTPgammaS of 3.2 nM.
      [35S]GTPgammaS autoradiography, performed in brain sections with the 5-HT1A
      agonist 8-OH-DPAT, revealed high levels of 5-HT1A-stimulated [35S]GTPgammaS
      binding in the hippocampus, lateral septum, prelimbic cortex, entorhinal cortex,
      and dorsal raphe nucleus. 5-HT1A-stimulated [35S]GTPgammaS binding in sections
      was blocked by the addition of the 5-HT1 antagonist methiothepin. These results
      show that the use of agonist-stimulated [35S]GTPgammaS autoradiography for the 5
      HT1A receptor system should provide new information regarding signal transduction
      in specific brain regions.

PMID- 9288831
TI  - Loss of inhibitory synapses on the soma and axon initial segment of pyramidal
      cells in human epileptic peritumoural neocortex: implications for epilepsy.
AB  - The peritumoural neocortex removed from epileptic patients represents an
      important region for research because of its possible relationship to the
      generation, maintenance, and propagation of seizures. The peritumoural neocortex
      removed from an epileptic patient showing a regrowth of an anaplastic astrocytoma
      was examined in detail using immunocytochemistry for gamma-aminobutyric acid,
      glutamic acid decarboxylase, parvalbumin, nonphosphorylated neurofilament
      protein, glial fibrillary acidic protein, and histocompatibility antigen HLA-DR.
      The patterns of immunostaining were compared with the cytoarchitecture and
      myeloarchitecture in adjacent sections, and with the patterns of immunostaining
      observed in normal control neocortex. Furthermore, quantitative electron
      microscopy was used to compare the synaptic densities of presumptive excitatory
      and inhibitory synapses between regions showing different grades of
      cytoarchitectural and neurochemical alterations in the peritumoural neocortex,
      and to compare these regions with normal neocortex. A variety of changes in
      synaptic circuits in the peritumoural neocortex was found, but it appears that
      neurons within the less abnormal-looking regions were involved in altered
      synaptic circuits that might contribute to epileptic activity. In these regions,
      the most prominent change was the loss of inhibitory synapses on the soma and
      axon initial segment of pyramidal cells, but numerous excitatory synapses were
      present on their dendrites that would make these neurons hyperexcitable. However,
      the most abnormal regions histologically were likely a primary zone for
      progression of the tumour, with many surviving neurones, but which received and
      formed very few synapses; thus, they were probably unrelated to the initiation,
      maintenance, or propagation of seizures.

PMID- 9288832
TI  - HIV-1 envelope glycoprotein 120 regulates brain IL-1beta system and TNF-alpha
      mRNAs in vivo.
AB  - Human immunodeficiency virus type I (HIV-1)-derived envelope glycoprotein 120
      (gp120) is proposed to play an important role in HIV-1 neuropathology. Gp120 may
      act through mediators including proinflammatory cytokines. Here, we investigated
      the regulation of the IL-1beta system [IL-1beta, IL-1 receptor type I (IL-1RI),
      IL-1 receptor antagonist (IL-1Ra)], TNF-alpha and TGF-alpha mRNAs in the rat
      central nervous system (CNS) in response to the constant intracerebroventricular
      (ICV) microinfusion of HIV-1 gp120 for 72 h and 144 h. The results show that
      gp120: (1) increased IL-1beta and IL-1Ra mRNAs levels in the same samples from
      the cerebellum, hypothalamus and midbrain, with the largest increase in the
      hypothalamus; (2) induced profiles of IL-1beta mRNA and IL-1Ra mRNA that were
      highly intercorrelated; (3) increased the hypothalamic TNF-alpha mRNA levels; and
      (4) did not affect the IL-1RI mRNA and TGF-alpha mRNA levels in any brain region.
      A dysregulation in the IL-1beta/IL-1Ra CNS balance and a mutual induction and
      synergistic activity of IL-1beta and TNF-alpha could result in a deleterious
      amplification cycle of cellular activation and cytotoxicity with implications to
      HIV-1-associated encephalitis, encephalopathy, and neurological manifestations.

PMID- 9288833
TI  - Deficient cation channel regulation in neurons from mice with targeted disruption
      of the extracellular Ca2+-sensing receptor gene.
AB  - This study presents evidence that a receptor sensitive to the concentration of
      extracellular Ca2+ (Ca[2+]o) (CaR) is functionally coupled to ion channels
      involved in modulation of neuronal excitability. This receptor is expressed in
      hippocampus and other brain regions, suggesting that it could mediate some of the
      well-recognized but poorly understood direct actions of extracellular Ca2+
      (Ca[2+]o) on neuronal function. The effects of polycationic CaR agonists on the
      activity of a nonselective cation channel (NCC) in cultured hippocampal neurons
      from wild-type mice and from mice homozygous for targeted disruption of the CaR
      gene (CaR -/-) were compared in this study. The CaR agonists, neomycin (100
      microM), spermine (300 microM), and elevation of Ca(2+)o from 0.75 to 3 mM,
      significantly increased the probability of channel opening (Po) in wild-type
      neurons. None of these agents, however, produced any effect on Po in neurons from
      mice lacking the CaR. The same NCC, however, could be activated by thapsigargin
      in neurons from both wild-type mice and CaR-deficient mice, most likely through
      an associated increase in the cytosolic free calcium concentration (Ca[i]). Thus
      the CaR regulates the activity of Ca2+-permeable NCC in hippocampal neurons and
      could potentially modulate key neuronal functions, including neurotransmission
      and neuronal excitability, via membrane depolarization.

PMID- 9288834
TI  - Lateralized attenuation of hypothalamic self-stimulation after injecting
      histamine synthesis blocker alpha-FMH into the E2 tuberomammillary subnucleus.
AB  - The tuberomammillary nucleus (TM), located in the posterior hypothalamic region,
      is the only known source of neuronal histamine. Unilateral lesions in the
      rostroventral part of this nucleus enhanced ipsihemispheric lateral hypothalamic
      self-stimulation behavior, suggesting that this region exerts inhibitory control
      over the neuronal systems related to reward or reinforcement processes. To
      examine whether the amplification of reinforcing stimulation following lesions of
      histamine synthesizing neurons is indeed histamine mediated, we blocked histamine
      synthesis unilaterally by injection of 200 microg alpha-fluoromethylhistidine
      into the E2 region of the TM, and assessed the effects on electrical self
      stimulation behavior in the lateral hypothalamus (LH) of rats. Based on the
      finding that TM lesions facilitated such self-stimulation behavior, we
      hypothesized that this treatment would have similar effects. Unexpectedly, there
      was a sharp decrease in the rate of ipsihemispheric lateral hypothalamic self
      stimulation following the injection of alpha-FMH compared to the contralateral
      hemisphere of treated animals as well as compared to the vehicle group. Response
      rates were most strikingly attenuated 1 h postinjection, but remained low over
      the whole 7 days of testing. Opposite behavioral effects of TM lesions and alpha
      FMH application have been reported previously, and the effectiveness of alpha-FMH
      in reducing brain histamine levels is known to differ between brain regions. The
      fact that the alpha-FMH injection affected self-stimulation only in the
      ipsilateral hemisphere rules out an interpretation of the results in terms of
      unspecific effects of the treatment on arousal and other performance variables,
      and, instead, indicates a functional interaction with a subsystem linked to
      lateral hypothalamic reinforcement processes.

PMID- 9288835
TI  - Peptide GEGLSS-like immunoreactivity in the rat central nervous system.
AB  - A rabbit antiserum was raised against the N-terminal fragment peptide, GEGLSS
      (Gly-Glu-Gly-Leu-Ser-Ser) of bovine neuropeptide AF (NPAF, A18Famide). NPAF is an
      octadecapeptide isolated from the bovine brain together with neuropeptide FF
      (NPFF). GEGLSS-like immunoreactivity was localized with immunofluorescence
      technique in colchicine-treated rats in neuronal cell bodies of the supraoptic
      (SON) and paraventricular (PVN) hypothalamic nuclei. A few neurons were also
      observed in the retrochiasmatic part of the SON. GEGLSS-like immunoreactivity was
      also localized to nerve terminals of the posterior pituitary. No GEGLSS-ir
      neuronal cell bodies were observed in the medial hypothalamus, in an area that
      contains NPFF-ir neurons. GEGLSS immunoreactivity was also seen in the fibers and
      terminals of nucleus of the solitary tract. We injected a retrograde tracer,
      fluorogold, to the posterior pituitary gland and visualized GEGLSS-ir neuronal
      cell bodies double-labeled with the tracer in SON, PVN, and SOR. The pituitary
      stalk transsection totally abolished the GEGLSS-ir structures from the posterior
      pituitary. Our results suggest that GEGLSS immunoreactivity in the rat brain has
      a more limited distribution than NPFF immunoreactivity. GEGLSS immunoreactivity
      was partially colocalized with arginine-vasopressin and oxytocin in neuronal cell
      bodies in the SON and PVN. Considering the fact that the known rat NPFF-NPAF
      precursor does not contain GEGLSS structure, the detected GEGLSS immunoreactivity
      may be derived from a previously unknown precursor.

PMID- 9288836
TI  - Intracerebroventricular administration of NPY increases sympathetic tone
      selectively in vascular beds.
AB  - NPY is widely distributed and has broad regulatory actions in the peripheral and
      central nervous system (CNS) and is especially important in the regulation of
      cardiovascular responses. CNS administered NPY has been demonstrated to produce
      both increases and decreases in cardiovascular tone. In this study we evaluated
      the effect of intracerebroventricular (ICV) administered NPY on cardiovascular
      tone, regional blood flow dynamics, as well as the mechanism of this action in
      normal animals. Male rats were instrumented with ICV cannulas and allowed to
      recover. At the time of the experiment the rats were anesthetized with
      urethane/chloralose and the femoral artery cannulated for blood pressure
      determinations. The abdomen was opened and Doppler flow probes were placed around
      the iliac, renal, and superior mesenteric artery. Mean arterial pressure (MAP),
      heart rate (HR), iliac, renal, and superior mesenteric flow, as well as the
      calculated iliac, renal, and superior mesenteric conductance were determined. ICV
      administered NPY resulted in an increase in MAP and HR, which was associated with
      decreased flows in the iliac and superior mesenteric vessels while increasing
      renal flow. Conductance was decreased in the iliac and superior mesenteric
      vascular beds but not the renal artery. ICV administration of NPY in the presence
      of a systemically administered alpha1-adrenergic inhibitor, prazosin, attenuated
      the NPY-mediated effects on MAP as well as vascular conductance in the iliac and
      superior mesenteric vessels. Additionally, ICV administration of NPY in the
      presence of a systemically administered beta1-adrenergic inhibition, atenolol,
      also attenuated the NPY-mediated increase in HR and MAP. Blood flow responses and
      iliac and superior mesenteric vascular conductance were also attenuated by
      atenolol pretreatment. In these studies we conclude that lateral ventricular
      administration of NPY acts to increase systemic MAP and HR and the response is
      mediated by an increase in sympathetic tone to the heart and especially the
      splanchnic and skeletal muscle vasculature.

PMID- 9288837
TI  - Accelerated fractionation: what is the price for speeding?

PMID- 9288838
TI  - The Klaas Breur Lecture. Radiation, hypoxia and genetic stimulation: implications
      for future therapies.
AB  - The cellular stress response, whereby very low doses of cytotoxic agents induce
      resistance to much higher doses, is an evolutionary defence mechanism and is
      stimulated following challenges by numerous chemical, biological and physical
      agents including particularly radiation, drugs, heat and hypoxia. There is much
      homology in the effects of these agents which are manifest through the up
      regulation of various genetic pathways. Low-dose radiation stress influences
      processes involved in cell-cycle control, signal transduction pathways, radiation
      sensitivity, changes in cell adhesion and cell growth. There is also homology
      between radiation and other cellular stress agents, particularly hypoxia. Whereas
      traditionally, hypoxia was regarded mainly as an agent conferring resistance to
      radiation, there is now much evidence illustrating the cytokine-like properties
      of hypoxia as well as radiation. Stress phenomena are likely to be important in
      risks arising from low doses of radiation. Conversely, exploitation of the stress
      response in settings appropriate to therapy can be particularly beneficial not
      only in regard to radiation alone but in combinations of radiation and drugs.
      Similarly, tissue hypoxia can be exploited in novel ways of enhancing therapeutic
      efficacy. Bioreductive drugs, which are cytotoxically activated in hypoxic
      regions of tissue, can be rendered even more effective by hypoxia-induced
      increased expression of enzyme reductases. Nitric oxide pathways are influenced
      by hypoxia thereby offering possibilities for novel vascular based therapies.
      Other approaches are discussed.

PMID- 9288839
TI  - Accelerated fractionation (AF) compared to conventional fractionation (CF)
      improves loco-regional control in the radiotherapy of advanced head and neck
      cancers: results of the EORTC 22851 randomized trial.
AB  - BACKGROUND AND PURPOSE: A 5 week-hyperfractionated and accelerated radiotherapy
      regimen without reduction of the total dose was developed to fight tumour
      repopulation during treatment and tumour hypoxia. The purpose of the study was to
      try to improve loco-regional control in high risk head and neck carcinoma treated
      with curative radiotherapy. METHODS AND MATERIALS: From 1985 to 1995, a
      randomised controlled trial of the EORTC Cooperative Group of Radiotherapy (EORTC
      22851) compared the experimental regimen (72 Gy/45 fractions/5 weeks) to standard
      fractionation and overall treatment time (70 Gy/35 fractions/7 weeks) in T2, T3
      and T4 head and neck cancers (hypopharynx excluded). The end-point criteria were
      local and loco-regional control, overall and disease-free survival, and acute and
      late toxicities. Five hundred twelve patients were accrued. RESULTS: Patients in
      the AF (accelerated fractionation) arm did significantly better with regard to
      loco-regional control (P = 0.02) resulting at 5 years in a 13% gain (95% CI 3-23%
      gain) in loco-regional control over the CF (conventional fractionation) arm. This
      improvement is of larger magnitude in patients with poorer prognosis (N2-3 any T,
      T4 any N) than in patients with more favourable stage. Multivariate analysis
      confirmed AF as an independent prognostic factor of good prognosis for loco
      regional control (P = 0.03). Specific survival shows a trend (P = 0.06) in favour
      of the AF arm. ACUTE AND LATE TOXICITIES: Acute and late toxicity were increased
      in the AF arm. Late severe functional irradiation damage occurred in 14% of
      patients of the AF arm versus 4% in the CF arm. Two cases of radiation-induced
      myelitis occurred after doses of 42 and 48 Gy to the spinal cord. CONCLUSIONS:
      This trial shows that accelerated radiotherapy improves loco-regional control in
      head and neck squamous cell carcinomas. A less toxic scheme should, however, be
      investigated and documented before using accelerated radiotherapy as a standard
      regimen of curative radiotherapy for head and neck cancers.

PMID- 9288840
TI  - A randomised multicentre trial of CHART versus conventional radiotherapy in head
      and neck cancer.
AB  - BACKGROUND AND PURPOSE: Continuous, hyperfractionated, accelerated radiotherapy
      (CHART) has shown promise of improved tumour control and reduced late morbidity
      in pilot studies and has now been tested in a multicentre randomised controlled
      clinical trial. MATERIAL AND METHODS: Patients with squamous cell cancer in the
      main sites within the head and neck region with the general exception of early T1
      N0 tumours were entered into the study by 11 centres. There was a 3:2
      randomisation to either CHART, where a dose of 54 Gy was given in 36 fractions
      over 12 days, or to conventional therapy where 66 Gy was given in 33 fractions
      over 6.5 weeks. A total of 918 patients were included over a 5 year period from
      March 1990. RESULTS: ACUTE MORBIDITY: Acute radiation mucositis was more severe
      with CHART, occurred earlier but settled sooner and was in nearly all cases
      healed by 8 weeks in both arms. Skin reactions were less severe and settled more
      quickly in the CHART treated patients. TUMOUR CONTROL AND SURVIVAL: Life table
      analyses of loco-regional control, primary tumour control, nodal control, disease
      free interval, freedom from metastasis and survival showed no evidence of
      differences between the two arms. In exploratory subgroup analyses there was
      evidence of a greater response to CHART in younger patients (P = 0.041) and
      poorly differentiated tumours appeared to fare better with conventional
      radiotherapy (P = 0.030). In the larynx there was evidence of a trend towards
      increasing benefit with more advanced T stage (P = 0.002). LATE TREATMENT RELATED
      MORBIDITY: Osteoradionecrosis occurred in 0.4% of patients after CHART and 1.4%
      of patients after conventional radiotherapy. The incidence of chondritis or
      cartilage necrosis was similar in both arms. Life table analysis showed evidence
      of reduced severity in a number of late morbidities in favour of CHART. These
      were most striking for skin telangiectasia, superficial and deep ulceration of
      the mucosa and laryngeal oedema. CONCLUSION: Similar local turnout control was
      achieved by CHART as compared with conventional radiotherapy despite the
      reduction in total dose from 66 to 54 Gy supporting the importance of
      repopulation as a cause of radiation failure. The effects seen in advanced
      laryngeal cancer and those related to histological differentiation need further
      study. Reduced late morbidity is a factor which together with patient preference
      should be considered in the decision as to the programme of radiotherapy to
      employ in the curative treatment of head and neck cancer.

PMID- 9288841
TI  - Does waiting time affect the outcome of larynx cancer treated by radiotherapy?
AB  - AIM: To determine the impact of waiting for radiotherapy on local control in
      early larynx cancer treated by radiotherapy alone. METHODS: Records of patients
      with T1 and T2, N0-2 larynx cancer were examined at three radiotherapy centres.
      Waiting time was defined in three ways, (1) time from biopsy to radiotherapy, (2)
      time from presentation to radiation department to start of radiotherapy and (3)
      the minimum of (1) and (2). Time to relapse was the major end point. RESULTS:
      There were 581 patients with a median follow-up of 6.8 years. Stage distribution
      was as follows: T1, 370; T2a, 106; T2b, 94; T2 unspecified, 11; N0, 563; N+, 18.
      Median times from biopsy, presentation and minimum time to treatment were 24, 16
      and 15 days, respectively. Ninety percent of minimum waiting times were < or = 31
      days. The median dose was 61 Gy in a median of 30 fractions over a median 46
      days. Local recurrence occurred in 126 patients. The actuarial recurrence free
      rate at 5 years was 77% (SE 2%). In a multivariate analysis the significant
      predictors of relapse were higher T stage, longer treatment duration and
      increasing field area. Waiting time was not significantly associated with local
      relapse. CONCLUSION: This study did not show longer waiting time to be a
      significant predictor of relapse in early larynx cancer. Other end-points which
      are relevant, such as quality of life, have not been examined. Longer treatment
      times were significantly associated with relapse.

PMID- 9288842
TI  - Analysis of risk factors for mandibular bone radionecrosis after exclusive low
      dose-rate brachytherapy for oral cancer.
AB  - BACKGROUND: Brachytherapy is widely adopted as an exclusive treatment of T1/T2
      oral cancer with a high probability of definitive cure. Therefore, any major
      complication, like mandibular bone necrosis, should be avoided. Many risk
      factors, either clinical or technical, have been considered in the literature.
      MATERIALS AND METHODS: One hundred consecutive interstitial iridium LDR
      treatments for early cancers of the tongue and floor of the mouth performed from
      January 1989 to November 1993 were reviewed. An analysis of some simple technical
      parameters (total dose, dose-rate, reference volume, linear activity, total
      reference kerma) was performed in order to identify the main physical risk
      factors. Moreover, total dose was recalculated as extrapolated responsive dose
      for normal tissue complications. RESULTS: Bone necrosis was observed in 10 out of
      100 patients with a median follow-up of 38 months. No significant incidence of
      this complication was observed when tumor site (mobile tongue versus floor of the
      mouth), dental status or total physical dose were considered. A significant
      correlation between the incidence of bone necrosis and two main parameters was
      found, i.e. dose-rate (P < 0.02) and reference volume (P < 0.05). CONCLUSIONS: A
      threshold value may be suggested both for dose-rate (50 cGy/h) and reference
      volume (25,000 mm3). Bone necrosis is clearly related to both these parameters
      since most cases (i.e. 80%) were observed in the subgroup over the volume and
      dose-rate threshold.

PMID- 9288843
TI  - Two-dimensional exit dosimetry using a liquid-filled electronic portal imaging
      device and a convolution model.
AB  - BACKGROUND AND PURPOSE: To determine the accuracy of two-dimensional exit dose
      measurements with an electronic portal imaging device, EPID, using a convolution
      model for a variety of clinically relevant situations. MATERIALS AND METHODS:
      Exit doses were derived from portal dose images, obtained with a liquid-filled
      EPID at distances of 50 cm or more behind the patient, by using a convolution
      model. The resulting on- and off-axis exit dose values were first compared with
      ionization chamber exit dose measurements for homogeneous and inhomogeneous
      phantoms in open and wedged 4,8 and 18 MV photon beams. The accuracy of the EPID
      exit dose measurements was then determined for a number of anthropomorphic
      phantoms (lung and larynx) irradiated under clinical conditions and for a few
      patients treated in an 8 MV beam. The latter results were compared with in vivo
      exit dose measurements using diodes. RESULTS: The exit dose can be determined
      from portal images with an accuracy of 1.2% (1 SD) compared with ionization
      chamber measurements for open beams and homogeneous phantoms at all tested beam
      qualities. In the presence of wedges and for inhomogeneous phantoms the average
      relative accuracy slightly deteriorated to 1.7% (1 SD). For lung phantoms in a 4
      MV beam a similar accuracy was obtained after refinement of our convolution
      model, which requires knowledge of the patient contour. Differences between diode
      and EPID exit dose measurements for an anthropomorphic lung phantom in an 8 MV
      beam were 2.5% at most, with an average agreement within 1% (1 SD). For larynx
      phantoms in a 4 MV beam exit doses obtained with an ionization chamber and EPID
      agreed within 1.5% (1 SD). Finally, exit doses in a few patients irradiated in an
      8 MV beam could be determined with the EPID with an accuracy of 1.1% (1 SD)
      relative to exit dose measurements using diodes. CONCLUSIONS: Portal images,
      obtained with our EPID and analyzed with our convolution model, can be used to
      determine the exit dose distribution with an accuracy of 1.7% (1 SD) for most
      clinically relevant situations. EPID exit dosimetry is therefore a good
      alternative for diode dosimetry. The EPID system is a powerful tool in a
      dosimetric quality control programme during high dose/high precision
      radiotherapy.

PMID- 9288844
TI  - Non-invasive tumour perfusion measurement by dynamic CT: preliminary results.
AB  - In 18 patients the perfusion of a malignant head and neck tumour was estimated
      using contrast enhanced dynamic computed tomography. The mean estimated perfusion
      was 75.5 ml/100 g/min, varying between 27.9 and 131.9. Eleven patients were
      treated with radiation therapy; the obtained perfusion rates were significantly
      different between tumours with a favourable and those with an unfavourable early
      outcome.

PMID- 9288845
TI  - Oxygen tension in human tumours measured with polarographic needle electrodes and
      its relationship to vascular density, necrosis and hypoxia.
AB  - BACKGROUND AND PURPOSE: The use of polarographic needle electrodes for
      measurement of oxygen tension (pO2) in tumours requires documentation of the
      validity of the method. In the present work the pO2 values measured
      polarographically with the Eppendorf pO2 histograph in human tumours were
      compared with the histological appearance of the tumour tissue, i.e. vascular
      density, fraction of necrosis and fraction of hypoxic tissue, to investigate
      whether the measurements reflected the expected pO2. MATERIALS AND METHODS: The
      pO2 was measured in cervix tumours in patients and in human melanoma xenografted
      tumours in athymic mice. Vascular density was determined in the cervix tumours by
      histological analysis of biopsies from the pO2 measurement tracks. Fraction of
      necrosis and fraction of hypoxic tissue, i.e. tissue binding the hypoxia marker
      pimonidazole, were determined in the melanomas by analysis of histological
      sections from the tumour planes in which the pO2 measurements were performed.
      RESULTS: The pO2 distributions showed large intratumour heterogeneity. In cervix
      tumours, tumour regions with vascular density (vascular length per unit tissue
      volume) in the range of 47-77 mm/mm3 showed higher pO2 than tumour regions with
      vascular density in the range of 20-47 mm/mm3, which in turn showed higher pO2
      than tumour regions with vascular density in the range of 0-20 mm/mm3. In
      melanomas, tumour regions in which necrosis and hypoxia constituted more than 50%
      of the tissue showed lower pO2 than other tumour regions. CONCLUSIONS: The pO2
      measured in the tumours was consistent with the histological appearance of the
      tissue in which the measurements were performed, suggesting that reliable pO2
      distributions of tumours can be obtained with polarographic needle electrodes.

PMID- 9288846
TI  - Hypoxia marker labeling in tumor biopsies: quantification of labeling variation
      and criteria for biopsy sectioning.
AB  - BACKGROUND AND PURPOSE: The error associated with using biopsy-based methods for
      assessing parameters reflective of the tumor microenvironment depends on the
      variability in distribution of the parameter throughout the tumor and the biopsy
      sample. Some attention has been given to intratumoral distribution of parameters,
      but little attention has been given to their intrabiopsy distribution. We
      evaluated the intrabiopsy distribution of CCI-103F, a 2-nitroimidazole hypoxia
      marker. MATERIALS AND METHODS: The hypoxia marker CCI-103F was studied in dogs
      bearing spontaneous solid tumors. Two biopsies were taken from each of seven
      tumors, for a total of 14 biopsies. Biopsies were serially sectioned and four to
      six contiguous slides from each 100-150 microm of the biopsy were used to
      formulate the best estimate of CCI-103F labeled area throughout the biopsy
      sample. One, two or four slides were then randomly selected from each biopsy and
      the labeled area, based on this limited sample, was compared to the estimate
      obtained from counting all available slides. Random sampling of slides was
      repeated 1000 times for each biopsy sample. RESULTS: CCI-103F labeling variance
      throughout the biopsy decreased as the estimated overall labeled area in the
      biopsy decreased. The error associated with estimating the overall labeled area
      in a biopsy from a randomly selected subset of slides decreased as the number of
      slides increased, and as the overall labeled area in the biopsy decreased. No
      minimally labeled biopsy was classified as unlabeled based on limited sampling.
      CONCLUSION: With regard to CCI-103F labeling, quantification of the labeled area
      in four randomly selected slides from a biopsy can provide, in most biopsies, an
      estimate of the labeled area in the biopsy within an absolute range of +/-0.05.

PMID- 9288847
TI  - Hypoxia-induced changes in radiation sensitivity in human melanoma cells:
      importance of oxygen-regulated proteins, adenylate energy charge and cell cycle
      distribution.
AB  - BACKGROUND AND PURPOSE: The effects of transient hypoxia on the radiation
      sensitivity of human tumour cells have so far been investigated only to a limited
      extent, and only up to 12 h after reoxygenation. We irradiated cells shortly
      after reoxygenation (<1 h) or at prolonged times after reoxygenation (24 h and 48
      h) in order to examine possible relationships between changes in radiation
      sensitivity on the one hand and changes in rates of synthesis of oxygen-regulated
      proteins, changes in energy metabolism and changes in cell cycle distribution on
      the other. MATERIALS AND METHODS: Four human melanoma cell lines (A-07, D-12, R
      18 and U-25) were included in the study. After hypoxia treatment (4 h or 16 h)
      and reoxygenation, cells were either irradiated as monolayers at a dose rate of
      2.0 cGy/min or prepared for protein analysis, energy charge measurements or flow
      cytometric measurements of DNA. RESULTS: U-25 was the only line that showed
      increased radiation sensitivity shortly after reoxygenation, possibly because of
      extensive energy depletion. A-07 was the only line that showed increased
      radiation sensitivity at prolonged times after reoxygenation, possibly because of
      hypoxia-induced changes in the cell cycle distribution. The rates of synthesis of
      oxygen-regulated proteins (GRP78, GRP94, HSP70 and HSP90) were transiently
      perturbed to a similar extent in all lines after hypoxia treatment. CONCLUSION:
      The radiation sensitivity of the human melanoma cell lines was changed only to a
      minor extent by transient exposure to hypoxia.

PMID- 9288848
TI  - Effects of carbogen plus fractionated irradiation on KHT tumor oxygenation.
AB  - BACKGROUND AND PURPOSE: Numerous studies have demonstrated improvements in the
      oxygenation of tumor cells following both irradiation and carbogen breathing. The
      current studies were initiated to measure the combined effects of carbogen
      inhalation plus single and multi-dose irradiation on tumor oxygen availability,
      to better define the underlying physiological relationships. MATERIALS AND
      METHODS: Using KHT murine sarcomas, radiation was delivered to the tumor-bearing
      legs of non-anesthetized mice. Tumors were quick-frozen prior to or following
      single or multifraction irradiation and carbogen breathing, and intravascular
      HbO2 saturation profiles were determined cryospectrophotometrically. RESULTS:
      HbO2 levels for blood vessels located near the tumor surface initially decreased
      following 10 Gy irradiation, then increased and remained elevated. Interior HbO2
      levels remained unchanged. Following 2.5 Gy, HbO2 changes were minimal. At 24 h
      following 10 Gy, HbO2 levels were significantly increased compared to non
      irradiated controls, and carbogen breathing produced no additional benefit. At 24
      h following five fractions of 2 Gy, HbO2 levels throughout the tumor volume were
      significantly higher in carbogen breathing animals than in air breathing
      controls. CONCLUSIONS: Although peripheral blood vessels demonstrated substantial
      improvements in oxygenation following irradiation, oxygen availability nearer the
      tumor center remained at very low levels. The utility of carbogen in enhancing
      tumor oxygen availability was maintained following five clinically relevant
      fractions. At higher doses, radiation-induced enhancements in HbO2 levels
      overshadowed the carbogen effect. For either air or carbogen breathing, a
      decrease in the percentage of vessels with very low oxygen content did not appear
      to be a major factor in the reoxygenation of the KHT tumor.

PMID- 9288850
TI  - Molecular aspects of cellular responses to radiotherapy.
AB  - Advances have been made in unravelling the molecular chains of cause and effect
      that determine cellular responses to radiotherapy, including cell cycle arrest,
      DNA repair and apoptosis. To begin with, cells must have mechanisms that enable
      them to sense DNA damage. Little was known about this until recently, when a DNA
      protein kinase (DNA-PK) system for detecting radiation-induced strand breaks was
      described. The ataxia telangiectasia (ATM) gene has amino acid sequence
      similarities to DNA-PK, raising the possibility that the ATM protein also
      functions in some way as a sensor of DNA damage. However, just knowing the DNA
      damage is present is not enough. Signals must be transmitted via afferent
      biochemical pathways to proteins, such as p53, that determine which cellular
      responses are activated. The responses include cell cycle arrest, apoptosis and
      DNA repair, all of which relate closely to loss of clonogenic capacity and the
      outcome of treatment in our patients.

PMID- 9288849
TI  - Erythema: goodbye LQ!

PMID- 9288851
TI  - Confirmation of a prognostic index for patients with inoperable non-small cell
      lung cancer.
AB  - BACKGROUND AND PURPOSE: The prognostic index derived from a group of 502 patients
      with inoperable stages I-IIIb non-small cell lung cancer (NSCLC) from 1974 to
      1981 has been tested in an independent population of patients with NSCLC from
      1989 to 1993 for the relationship between this index and survival. MATERIALS AND
      METHODS: This recent population comprised 210 patients treated with radiotherapy;
      for staging and treatment planning more advanced technology (CT-imaging, CT-based
      dose-planning) was used. The five most powerful determinants, established in the
      previous study, were disease extent, clinical symptom score by Feinstein,
      performance status, tumour size and haemoglobin level. These key prognostic
      variables of the index had equal impact on survival. Thus, based only on the
      number of adverse factors, the patient falls into one of the six possible
      prognostic groups. RESULTS: In the present study we verified with the new patient
      material that the index applies to patients with inoperable NSCLC. All five
      factors were significantly predictive of survival and the inclusion of the other
      known prognostic variables in the multivariate analyses did not result in any
      further improvement. Furthermore, the composite index turned out to be as
      informative as the five variables separately and the index discriminates
      effectively between the low and high risk groups. Ninety-eight patients (47%)
      with three or more risk factors had a 2-year survival rate of less than 2%,
      whereas 17 patients (8%) with no risk factor had a survival of 53% during a
      minimum follow up of 2 years. CONCLUSIONS: As each of the five variables has the
      advantage of being routinely available the index is simple and can easily be used
      to guide management in daily clinical practice. The scoring system may also help
      to design new treatment strategies and facilitate the comparison of different
      studies.

PMID- 9288853
TI  - Volume and dose parameters for survival of non-small cell lung cancer patients.
AB  - BACKGROUND AND PURPOSE: To determine the effect of tumor volume and dose factors
      derived from 3-D treatment planning dose distributions on survival outcome for
      non-small cell lung cancer patients. MATERIALS AND METHODS: Seventy-six
      consecutive patients diagnosed with medically inoperable or locally advanced,
      unresectable non-small cell lung cancer planned with 3-D treatment planning
      between 1986 and 1992 were the subject of this retrospective study. Patient
      characteristics and dosimetric parameters were analyzed for influence on overall
      survival and local progression-free survival (LPFS) using univariate and
      multivariate analysis. RESULTS: Nodal stage and stage were the most significant
      factors for overall survival and LPFS duration on both univariate and
      multivariate analysis. We found a wide range of primary tumor volume sizes for
      each stage. Patients with tumor volumes <200 cm3 had longer survival (P = 0.047).
      In an analysis stratifying patients into four groups by tumor volume (<200 cm3
      versus >200 cm3) and nodes (negative versus positive), patients in the group with
      no nodal disease and <200 cm3 tumor volumes survived longer than patients in any
      other group (P = 0.046). No dose factors were statistically significant for
      longer survival. Longer LPFS was seen for (a) isocenter dose >70 Gy (P = 0.055)
      for the overall group of patients, (b) within a subgroup with no nodal disease
      and >73 Gy (P = 0.054), and (c) within a subgroup with no nodal disease and tumor
      volume <200 cm3 receiving >73 Gy (P = 0.086). CONCLUSIONS: Several findings from
      the volume and dosimetric analysis in this study are noteworthy. Stage was found
      to be a poor predictor of primary tumor volume size. Also, tumor volume size
      (<200 cm3) in conjunction with nodal status (negative nodes) had an impact on
      survival though there was a mix of stage (I, IIIa, IIIb) in this group of
      patients. Finally, dose appears to influence local control (LPFS) for the overall
      group of patients and when tumor volumes are <200 cm3. Our data indicate that
      outcome following radiation may be better predicted by a staging system that
      takes into account tumor volume and nodal spread rather than a system that is
      largely based on anatomic location of disease. Dose prescription for lung cancer
      treatment might better be written based on tumor volume size.

PMID- 9288852
TI  - Promising survival with three-dimensional conformal radiation therapy for non
      small cell lung cancer.
AB  - PURPOSE: Local failure is a major obstacle to the cure of locally advanced non
      small-cell lung cancer. Three-dimensional conformal radiation therapy (3-DCRT)
      selects optimal treatment parameters to increase dose to tumor and reduce normal
      tissue dose, potentially representing an enhancement of the therapeutic ratio of
      radiation therapy for lung cancer. We performed this analysis of 45 non-small
      cell lung cancer patients treated with 3-DCRT alone, to evaluate the ability of
      computer derived lung dose volume histograms to predict serious pulmonary
      toxicity, to assess the feasibility of this approach, and to examine the
      resulting survival. METHODS: There were 28 males (62%) and 17 females (38%). The
      median age was 65 (range: 38-82). Tumor stage was Stage I/II in 13%, IIIa in 42%,
      and IIIb in 44%. The histology was squamous in 44%, adenocarcinoma in 36%, and
      other non-small cell histologies in the others. Only 47% of patients. had
      combined favorable prognostic factors (i.e. KPS < or = 80, and < or = 5% wt.
      loss). The median dose of radiation to gross disease was 70.2 Gy (range: 52.2-72
      Gy) delivered in fractions of 1.8 Gy, 5 days per week. RESULTS: Seven patients
      did not complete 3-DCRT due to disease progression outside the port. Follow-up
      data are mature: the median follow up of the 6 survivors is 43.5 months (35-59).
      Thoracic progression occurred in 46%. Median survival (all 45 patients.) is 15.7
      months and survival is 32% at 2 years and 12% at 59 months. Pulmonary toxicity >
      or = grade 3 occurred in 9% of patients. Dose volume histograms were available in
      31 patients and showed a correlation between risk of pulmonary toxicity and
      indices of dose to lung parenchyma. Grade 3 or higher pulmonary toxicity occurred
      in 38% (3/8) of patients with > 30% of lung volume receiving > or = 25 Gy, versus
      4% (1/23) of patients with < or = 30% lung receiving > or = 25 Gy (P = 0.04).
      Grade 3 or higher pulmonary toxicity occurred in 29% (4/14) of patients with a
      predicted pulmonary normal tissue complication probability of 12% or higher
      versus 0% (0/17) in patients with a predicted probability of less than 12% (P =
      0.03). CONCLUSIONS: Despite adverse prognostic criteria median survival is
      encouraging and may be higher than some combined modality approaches. Dose volume
      histogram parameters may be useful to determine the maximum dose for individual
      patients and thereby permit avoidance of toxicity.

PMID- 9288854
TI  - Acute changes in peak expiratory flow rate following palliative radiotherapy for
      bronchial carcinoma.
AB  - PURPOSE: Changes in respiratory function occurring in the months and years
      following radiotherapy have been well documented. The changes that occur in the
      hours after treatment are less clear, we report a study that recorded peak
      expiratory flow rate (PEFR) in the 72 h following radiotherapy to the mediastinum
      and large airways. METHODS: Fifty-six patients with carcinoma affecting the major
      bronchii were recruited; 39 were male, with a median age of 66 years; 49 had
      histologically confirmed lung cancer. The median baseline PEFR was 300 1/s
      (range: 120-600). Patients were asked to record home PEFR readings in the 72 h
      that followed the first fraction of radiotherapy. Doses ranges from an 8-Gy
      single fraction to 60 Gy in 30 fractions. RESULTS: Forty-nine patients recorded a
      fall in PEFR (3%-60% of the baseline value) in the 24 h after radiotherapy, the
      mean for all 56 patients was a fall of 20.3% (95% confidence interval -15.8% to 
      24.8%). These lowest values occurred a median time of 6 h after treatment (range:
      2-24 h). By 72 h the mean PEFR had returned to the baseline. Tumour site (central
      or lobar bronchus) and fraction size (<3 GY or >3 Gy) had no significant effect
      on the fall in PEFR (Mann-Whitney U-test P = 0.15 and P = 0.06, respectively).
      CONCLUSION: We conclude that a fall in PEFR can occur after radiotherapy
      treatment to the mediastinum. This is of concern in patients being treated for
      bronchial carcinoma whose respiratory function may already be compromised.

PMID- 9288855
TI  - Effect of irradiated volume on lung damage in pigs.
AB  - BACKGROUND AND PURPOSE: The volume dependence of radiation induced lung damage is
      of important clinical concern. The aim of the present study was to investigate
      the effect of irradiated volume on radiation pneumonitis and lung fibrosis in
      pigs after fractionated irradiation. MATERIALS AND METHODS: Twenty-five animals
      were irradiated with 10 x 14 cm2 fields to the whole right lung (about 530 cm3),
      while 19 animals received irradiation only to the lower part of the right lung
      (10 x 8 cm2 fields, about 260 cm3). The irradiations were given in five fractions
      over 5 days with total doses ranging from 14.3-38.0 Gy (whole lung) or 21.3-31.2
      Gy (half lung) using a 60cobalt unit and an isocentric technique. Early lung
      damage was assessed during the first 8 weeks after the start of treatment by
      weekly chest radiographs and by twice weekly determinations of the breathing rate
      in resting animals. Fibrosis was quantified at autopsy (after 8 weeks or after 5
      8 months) by histological evaluation and by determination of the hydroxyproline
      content of the lung tissue. Based on reference values obtained in 17 untreated
      control animals the experimental data were converted to quantals for probit
      analysis. RESULTS: The data did not indicate any significant differences for the
      incidence of lung damage after half lung and whole lung irradiation when injury
      was assessed by radiography, histology, or hydroxyproline content. However, using
      an increase in breathing rate as experimental endpoint, significant differences
      of radiation induced morbidity were observed. While none of the animals after
      half lung irradiation showed pathological breathing rates even after doses of 29
      Gy and 31 Gy, a clear if shallow dose-response relationship with an ED50-value of
      27 +/- 11 Gy (SD) was obtained after whole lung irradiation (P < 0.01).
      CONCLUSIONS: A volume effect can only be demonstrated for functional lung
      morbidity whereas induction of structural lung damage is independent of the
      volume irradiated.

PMID- 9288856
TI  - Plasma TGFbeta level in rats after hemithoracic irradiation.
AB  - Changes in TGF-beta plasma levels were observed 18 weeks after hemithoracic
      irradiation in rats. This coincides with an increase in the breathing frequency.
      being most pronounced between 22 and 28 weeks after irradiation. The correlation
      suggests a potential role of the circulating TGF-beta in the monitoring of
      localized radiation-induced lung injury.

PMID- 9288857
TI  - Combined endoluminal and external irradiation of inoperable oesophageal
      carcinoma.
AB  - PURPOSE: Higher radiation doses to oesophageal cancer might be possible by the
      steep dose gradient of an afterloading source. Structures at risk are not
      impaired by endoesophageal brachytherapy. Our experiences with endoesophageal
      afterloading in combination with external beam treatment are reported. METHODS
      AND MATERIALS: Fifty-four patients were treated by this technique. All patients
      suffered from an inoperable oesophageal carcinoma (7 adenocarcinoma, 47 squamous
      cell carcinoma). Patients were scheduled by tumour stage and medical condition
      into a curative group (21 patients) and into a palliative group (33 patients).
      Mean sum doses of 60.3 Gy (range 58-70 Gy) percutaneously and an additional
      endoluminal dose of 13.6 Gy (range 10-20 Gy) were applied endoluminally in the
      curative group and 44.9 Gy (range 14-53 Gy) plus 17.5 Gy (range 5-30 Gy),
      respectively, in the palliative group. Overall treatment time was 10 weeks (range
      4.6-14.3 weeks) for the curative group and 9.3 weeks (range 4.1-13.9 weeks) for
      the palliative group. RESULTS: Six weeks after the end of therapy a radiological
      remission could be observed in 32/33 of the palliatively treated patients (10
      complete, 22 partial, 1 none). In 13 patients of this group a local progression
      was observed after a median time of 7.1 months. Median survival of this group was
      9 months. A radiological remission occurred in 18/21 of the curatively treated
      patients (11 complete, 7 partial, 3 none). Median time to local progression (12
      patients) was 4.5 months in this group and median survival was 7.7 months. The
      difference in time to progression reached a significant level (P = 0.05). The
      only favourable factors for survival were an incomplete or complete radiological
      remission (median survival 7.5 versus 11.4 months, P = 0.003) and stage I/II or
      III/IV (median survival 7.4 versus 12.6 months, P = 0.0024). The prior estimation
      of the treatment goal was not confirmed by survival data (curative, 7.7 months
      versus palliative, 9.0 months (not significant)). Eight of 54 minor and 8/54
      (15%) major adverse events were observed. In four of these patients major
      complications were caused by progressive tumour. CONCLUSIONS: Endoesophageal
      afterloading combination with percutaneous irradiation is a feasible save
      treatment in inoperable cases. A good local tumour regression and functional
      results can be reached. The data suggest that higher endoluminal doses extend the
      time to local progression. In comparison with the literature survival can not be
      increased by this treatment technique. The best way to combine both treatment
      modalities has not yet been found.

PMID- 9288858
TI  - Treatment outcome following radiotherapy in elderly patients with bladder cancer.
AB  - BACKGROUND AND PURPOSE: The optimal treatment of elderly patients with bladder
      cancer is not established. This study aimed to evaluate prognostic variables for
      survival and morbidity, which may be important for treatment strategy. MATERIAL
      AND METHODS: The medical records of 94 patients aged > or = 75 years receiving
      curatively intended radiotherapy for bladder cancer were reviewed
      retrospectively. RESULTS: Median age was 78 years (range 75-93 years). Fifty
      patients had T1-2 tumors, and 42 patients had T3-4 tumors. The total planned dose
      was 57.6-62.6 Gy in 24-30 fractions in 6 weeks. In 76 patients, a 2 week rest
      period was planned after 16 fractions (split course). Half of the patients were
      hospitalized during or after the treatment because of gastrointestinal or
      urogenital side effects. Median survival was 13.9 months (range 0.6-150.0 +
      months), 29% survived for 2 years and 7% survived for 5 years. Patients aged > 78
      years survived for a shorter period than patients aged 75-78 years (13.4 versus
      16.1 months). Univariate survival analysis revealed that low stage (T1-2), good
      performance status (PS < or = 1), split course treatment, no treatment
      interruption due to side effects, and no hospitalization during treatment were
      associated with long survival. In multivariate analyses, T-stage, split course
      treatment, and performance status were independent prognostic factors.
      CONCLUSION: The results confirm that curative intended radiotherapy is feasible
      in elderly patients, but patients with stage T3-4 and PS > 1 have a short
      survival. These patients should be offered palliative treatment.

PMID- 9288859
TI  - A randomized double blind placebo controlled multicenter study of mesalazine for
      the prevention of acute radiation enteritis.
AB  - BACKGROUND AND PURPOSE: Symptoms of acute radiation enteritis (ARE), dominated by
      diarrhea, occur in more than 70% of patients receiving pelvic irradiation.
      Eicosanoids and free radicals release have been implicated in the pathogenesis.
      Mesalazine (5-ASA) is a potent inhibitor of their synthesis in the mucosa and
      could therefore be of some interest in preventing ARE. PATIENTS AND METHODS: The
      study was performed in six radiotherapy units in France who agreed on
      standardized irradiation procedures. One hundred and fifty-three patients planned
      for external beam radiotherapy to the pelvis > or = 45 Gy for prostate (n = 97)
      or uterus (n = 54) cancer were randomized on a double blind basis to receive
      prophylactic 5-ASA (4 g/day Pentasa) or placebo. Patients with concomitant
      chemotherapy were excluded. Prostate and uterus cancers were chosen since these
      centropelvic tumors require a similar radiotherapy protocol during the first step
      of treatment and involve a comparable volume of small intestine. The symptoms of
      ARE and their severity were assessed every week during irradiation, and 1 and 3
      months after its end. All patients followed a low fiber and low lactose diet. End
      points were diarrhea, use of antidiarrheal agents, abdominal pain, and body
      weight. Effficacy was evaluated using intention to treat. RESULTS: (means +/- SD)
      Groups did not differ for age (mean 64 +/- 9 years), sex, tumor site, or
      irradiation procedure. During irradiation, diarrhea occurred in 69% and 66% of
      the 5-ASA and placebo groups, respectively (chi2, P = 0.22). Curves of survival
      without diarrhea did not differ between groups (logrank P = 0.09). Severity of
      diarrhea did not differ between groups except at d15 where it was significantly
      more severe in the 5-ASA group (ANOVA P = 0.006). Duration of diarrhea did not
      differ (22 +/- 15 days in both groups, P = 0.88). Abdominal pain was less
      frequently reported in the 5-ASA group at d28 (34% vs. 51%, P = 0.048). Use of
      antidiarrheal agents and body weight did not differ between groups. CONCLUSION:
      Mesalazine 4 g/day did not decrease the symptoms of ARE.

PMID- 9288860
TI  - Is the loss of endothelial thrombomodulin involved in the mechanism of chronicity
      in late radiation enteropathy?
AB  - BACKGROUND AND PURPOSE: Radiation enteropathy is characterized by locally
      elevated levels of inflammatory and fibrogenic cytokines. Microvascular injury
      may sustain these alterations through persistent local hypercoagulopathy,
      platelet aggregation, leukocyte adhesion and release of biologically active
      mediators. This study assessed the relationship of endothelial thrombomodulin
      (TM), a key regulator of the protein C anticoagulant pathway and marker of
      endothelial function, with transforming growth factor beta (TGF-beta)
      immunoreactivity and morphologic alterations in radiation enteropathy. MATERIALS
      AND METHODS: Small bowel resection specimens from 9 patients with radiation
      enteropathy were analyzed by computerized quantitative immunohistochemistry using
      antibodies against TM, von Willebrand factor (vWF) and TGF-beta. Identical
      measurements were performed on intestinal resection specimens from otherwise
      healthy penetrating trauma victims and on archived small intestines. A previously
      validated image analysis technique was used to assess submucosal vessels for TM
      and vWF immunoreactivity, and the intestinal wall for total extracellular matrix
      associated TGF-beta immunoreactivity. RESULTS: Specimens from irradiated patients
      showed prominent submucosal and subserosal thickening and fibrosis, and
      obliterative vasculopathy. Control specimens were histopathologically normal.
      Vascular density and vWF immunoreactivity were similar in radiation enteropathy
      patients and controls. The image-analysis techniques were highly reproducible,
      with correlation coefficients for repeated measurements ranging from 0.86 to
      0.93. Radiation enteropathy specimens exhibited a highly significant reduction in
      the number and proportion of TM-positive submucosal vessels per unit area (P <
      0.0001) and increased intestinal wall TGF-beta immunoreactivity (P = 0.002).
      CONCLUSIONS: These data support the theory that sustained endothelial dysfunction
      is involved in the molecular pathogenesis of radiation enteropathy, and point to
      TM as important in the chronic nature of radiation enteropathy and a potential
      target for prophylactic and therapeutic interventions.

PMID- 9288861
TI  - Reconstruction accuracy of a dedicated localiser for filmless planning in intra
      operative brachytherapy.
AB  - BACKGROUND AND PURPOSE: With the use of HDR and PDR afterloaders containing a
      single stepping source, brachytherapy dose distributions can be optimised by
      varying the source dwell time. With the goal of implementing 'conformal
      brachytherapy', i.e. ensuring that the dose distribution conforms as accurately
      as possible to the target volume, we evaluated a set-up which enabled on-line
      implant localisation and dose planning during implantation. MATERIALS AND
      METHODS: The set-up, designated as an integrated brachytherapy unit (IBU),
      consists of a shielded operating room equipped with an HDR afterloader and a
      dedicated brachytherapy localiser connected to a treatment planning computer. The
      localiser is isocentric and has an extra degree of freedom in comparison to
      conventional simulators (i.e. an L-arm in combination with a C-arm) and enables
      viewing of the implant from any direction. A reconstruction algorithm which takes
      into account both rotation axes, i.e. the L-arm and C-arm angle, was developed
      for the localiser. The reconstruction procedure was tested by using the IBU
      localiser to measure the reconstruction accuracy with a phantom (containing 25
      markers at well defined positions) and using reconstruction from radiographs.
      These results were compared to simulations where the accuracy of reconstruction
      was determined as a function of the reconstruction angle and the accuracy of read
      outs of the localiser settings. On-line localisation and dose planning during
      implantation is based on filmless planning, i.e. fluoroscopy images and the
      corresponding localiser settings are imported into the treatment planning
      computer during implantation. The accuracy of filmless planning was determined
      using fluoroscopy images in the same set-up as for the experiments with the
      radiographs. The effect of reconstruction inaccuracies on the total irradiation
      time and the dose in target or normal tissue points was elucidated for clinically
      relevant implant geometries. The treatment plans of two phantoms based on
      reconstruction from films as well as fluoroscopy images were compared with plans
      for implants defined by exact co-ordinates. RESULTS: The average reconstruction
      error due to the accuracy of the read-out of the localiser settings varied
      between -0.18 and 0.24 mm, with a standard deviation (arising from digitisation
      errors) ranging from 0.11 to 0.22 mm. Using filmless reconstruction and the 10
      inch field of view of the image intensifier (without applying correction for the
      geometric distortions) the average reconstruction error ranged from 0.01 to 0.65
      mm, and the standard deviation ranged from 0.40 to 0.73 mm. These errors arose as
      a consequence of the finite pixel size and geometric distortions. These limited
      errors did not influence the treatment time for clinical implant geometries and
      had only a minor effect (<1%) on the dose in markers during filmless planning.
      CONCLUSION: This IBU set-up, with a dedicated brachytherapy localiser, allows for
      a rapid and accurate filmless planning procedure based on implant localisation
      from fluoroscopy images.

PMID- 9288862
TI  - Patterns of dose variability in radiation prescription of breast cancer.
AB  - PURPOSE: Comparison of radiation outcome of various treatment protocols is
      difficult due to the variability of dose prescription. A retrospective analysis
      of the pattern and intercomparison of dose prescriptions is presented for the
      treatment of breast cancer. MATERIALS AND METHODS: To represent the clinical
      practice for breast irradiation with tangential fields, commonly used
      prescription points were chosen that lie on the perpendicular bisector of the
      chest wall separation (s) that represents the breast apex height (h). These
      points are located at 1.5 cm from the posterior beam edge, at the chest wall-lung
      interface (2-3 cm), at distances of h/3 and h/2, and at the isocenter. One
      hundred consecutive patients treated with intact breast following excisional
      biopsy were used in this study. For analysis, treatment planning was carried out
      without lung correction with a 6 MV beam for all patients, even though some of
      the patients were treated with high energy beams for dose uniformity. Dose
      distributions were optimized with wedges and beam weights to provide a
      symmetrical dose distribution on the central axis plane. The statistical analyses
      of the different parameters, s, h, maximum dose, and doses at various
      prescription points were carried out. RESULTS: The maximum dose (hot spot) in
      breast varied from +5% to +27% above the prescribed dose among the patient
      population. The hot spot was directly related to s, and appeared to be
      independent of h and the ratio h/s. Among 55%, 40%, and 5% of the patients, the
      magnitude of the hot spot was 5-10%, 10-15%, and >15%, respectively. Except for
      the magnitude of the hot spot, the doses at various prescription points were
      independent of the breast size. For a prescription point at h/3 or at the lung
      chest wall interface, the dose variation within +/- 1% is observed for 90% of the
      patient population. On the other hand, the average dose variation is about +/- 3%
      among other protocols with dose prescription point varying up to the h/2 point.
      With the prescription point at the isocenter, an average and maximum variation of
      4-5% and 11% were observed, respectively. The maximum dose inhomogeneity for some
      patients was significantly higher, i.e. up to +27% even without the lung
      correction. CONCLUSIONS: A wide variation in prescription dose is observed among
      the different treatment protocols commonly used in breast treatment. For a total
      dose of 46-50 Gy delivered at 2 Gy/fraction to the breast, the prescribed dose
      may vary between 50 and 55 Gy and the hot spot dose per fraction may range
      between 2.3 and 2.5 Gy depending on the protocol and breast size. Thus dose
      normalization at hot spot and the isocenter should be discouraged unless the
      total dose to the breast is modified. A uniform definition of dose prescription
      for breast treatment is greatly required for intercomparison of clinical data.

PMID- 9288863
TI  - Mediastinal irradiation in lung cancer three years after heart transplantation: a
      case report.

PMID- 9288864
TI  - The need for the development of therapeutically combined artificial organs.

PMID- 9288865
TI  - Errors in the selection of dialysate concentrates cause severe metabolic acidosis
      during bicarbonate hemodialysis.
AB  - Severe metabolic acidosis occurred during bicarbonate hemodialysis as the result
      of an error made in the selection of the dialysate concentrate. We questioned
      whether or not it was possible for the dialysis equipment to regulate the
      proportions in the dialysate fluid using an incorrect dialysate concentrate and
      still obtain the proper conductivity. We simulated this situation in vitro and
      found that during bicarbonate dialysis an inappropriately acidic dialysate fluid
      could replace the normal dialysate with an adequate range of conductivity still
      being maintained and therefore no triggering of alarms. The investigation showed
      that the dialysis machines were not adequately adjusted for sensitivity to the
      concentrates being employed during dialysis. We concluded that dialysis equipment
      should be fitted with on-line pH meters with alarm systems.

PMID- 9288866
TI  - Proportional changes in body fluid with hemodialysis evaluated by dual-energy X
      ray absorptiometry and transthoracic bioimpedance with particular emphasis on the
      thoracic region.
AB  - Alterations in body composition during extracorporeal hemodialysis (HD) were
      investigated in 12 hemodialysis patients (9 males and 3 females, mean age 50 +/-
      15 years) with a mean ultrafiltration of 2.6 +/- 1.0 L. Analysis was performed
      using a dual-energy x-ray absorptiometry technique (DXA), which measures 3
      principal components of the body: fat mass (FM): lean body mass (LBM), i.e., all
      soft tissues excluding fat; and bone mineral content (BMC). These 3 components
      were calculated for the whole body and for different body regions (namely, the
      thorax, trunk, lower limbs, and upper limbs). The thoracic cage region could be
      defined manually, separately from the trunk, and its tissue composition was
      calculated. DXA analysis was performed concomitant with a measurement of the
      basal thoracic impedance (TFI) by bioimpedance cardiography prior to and 1 h
      after dialysis. We found a significant decrease in the total LBM, from 55.8 +/-
      8.8 to 53.3 +/- 9.3 kg (p < 0.05), but no change in either the FM or BMC.
      Moreover, there was a disproportional reduction in the LBM in different regions,
      being significantly greater in the thorax (7.47 +/- 3.7%) than in the other body
      regions (trunk 4.3 +/- 2.0%, lower limbs 5.4 +/- 2.1%, and upper limbs 4.7 +/-
      1.5%). Regarding bioimpedance, a stronger significant correlation was detected
      between the percentage changes in the TFI and the changes in thoracic fluid (r =
      0.80, p < 0.01) than between the changes in the TFI and the changes in the total
      body fluid (r = 0.63, p < 0.01). The absolute values of the TFI were also
      significantly and negatively correlated to the thoracic lean mass to fat mass
      ratio, both before and after HD (r = 0.82, p < 0.001 and r = 0.86, p < 0.001,
      respectively). In conclusion, DXA is a very sensitive technique to detect fluid
      changes during HD in the thorax when the thoracic cavity is defined as a region
      of interest as well as for the whole body. The data also indicate an
      extracellular compartmental imbalance between different regions with a
      significantly greater change in the thoracic region. Transthoracic bioimpedance
      is a useful technique for evaluating the HD induced changes in the thoracic
      fluid, rather than total body fluid.

PMID- 9288867
TI  - LDL hemoperfusion--a new procedure for LDL apheresis: first clinical application
      of an LDL adsorber compatible with human whole blood.
AB  - To date, lipid apheresis procedures can remove low-density lipoprotein (LDL)
      cholesterol (LDL-C) only from plasma. Thus, initially plasma has to be separated
      from the blood cells, which increases the costs and complexity of the
      extracorporeal circuit. This paper describes the first clinical application of a
      new LDL adsorber that eliminates LDL directly from whole blood. The goal of this
      pilot study was to test the efficacy, safety, and feasibility of direct
      lipoprotein adsorption in patients. In a 2 center Phase II clinical trial, 12
      hypercholesterolemic patients suffering from overt coronary or peripheral artery
      disease were treated once with LDL hemoperfusion. The new LDL adsorber (DALI,
      Fresenius, St. Wendel, Germany) contained 480 ml of polyacrylate coated
      polyacrylamide gel. The anticoagulation consisted of an initial heparin bolus
      followed by an acid citrate dextrose (ACD)-A infusion during the treatment. The
      processing of nearly 1 patient blood volume resulted in a reduction of LDL-C by
      45 +/- 8% and triglycerides by 23 +/- 20%. HDL-C, fibrinogen, and cell counts
      were not significantly influenced. In a subgroup of 5 patients who exhibited
      elevated lipoprotein (a) (Lp[a]) levels, Lp(a) reduction was 43 +/- 15% (all
      results corrected for plasma volume shifts). The sessions were clinically
      uneventful; the system was technically safe and easily handled. In conclusion,
      short-term LDL hemoperfusion by the DALI proved to be a safe, effective, and
      simple procedure for the treatment of patients suffering from symptomatic
      recalcitrant hypercholesterolemia. The present study represents a solid basis for
      the clinical long-term evaluation of this new technique in the future.

PMID- 9288868
TI  - Cyclosporine and therapeutic plasma exchange in treatment of progressive
      autoimmune diseases.
AB  - Despite treatment with intensive immunosuppressive drug regimens, the prognosis
      of patients suffering from severe progressive autoimmune diseases like systemic
      lupus erythematosus (SLE), nephrotic syndrome (NS), and Behcet's disease is poor.
      Side effects (infections and malignant tumors) often occur. In the present trial,
      35 patients suffering from autoimmune diseases (SLE, n = 21; NS, n = 10; and
      Behcet's disease, n = 4) were treated for 3.7 +/- 2.0 years with 2.5 +/- 0.6 mg
      cyclosporine/kg body weight/day in addition to corticosteroids alone or in
      combination with azathioprine and/or cyclophosphamide. In active stages of the
      diseases with extremely high concentrations of anti-ds-DNA-antibodies,
      antinuclear antibodies, circulating immunocomplexes, and reduced complement
      concentrations, therapeutic plasma exchange (TPE) has been applied. Compared with
      previous treatment modalities, significantly (p < 0.05) more effective and rapid
      reductions of the antibodies were reached. Clinical disorders improved within 1-6
      weeks. All patients reported increased performance and a better quality of life.
      After 1-12 months, the previously required doses of immunosuppressive drugs and
      the frequency of TPE could be reduced by 40-100%. After 13.4 +/- 11.8 months in
      17 of 35 patients (8 with SLE, 5 with NS, 4 with Behcet's disease), cyclosporine
      was established as the monotherapy. No severe side effects were registered. In
      treating active stages of severe progressive autoimmune diseases and forms with
      persistent high antibody levels, the addition of TPE to conventional therapy was
      very effective, as observed in both clinical and laboratory parameters.

PMID- 9288869
TI  - Granulocytapheresis in the treatment of patients with rheumatoid arthritis.
AB  - The G-1 column is an extracorporeal type granulocytapheresis device packed with
      220 g cellulose acetate beads to which granulocytes and monocytes specifically
      adhere. A total of 59 rheumatoid arthritis patients with elevated granulocyte
      counts from 4 hospitals in Japan received 2 apheresis sessions of 1 h
      duration/week for a total of 8 times over a period of 4 weeks. About 55% of the
      leukocytes which entered the G-1 column were adsorbed onto the beads: 95% were
      granulocytes, 3.5% monocytes, and 0.4% lymphocytes. Clinical and efficacy
      assessments showed improvements in swollen joints (p < 0.01), tender joints (p <
      0.001), the active joint score (p < 0.001), duration of morning stiffness (p <
      0.01), and grip strength (p < 0.001). In good responders, the improvements were
      observed for up to 12 weeks following the last apheresis. Exacerbation was noted
      in 2 patients. It is suggested that the efficacy of the G-1 column is
      attributable to the removal or suppression of hyperactive leukocytes and
      inflammatory cytokines, inducing a kind of immunomodulation.

PMID- 9288870
TI  - Tissue reactions to various percutaneous materials with different surface
      properties and structures.
AB  - Tissue responses to various percutaneous materials with different surface
      properties and structures were investigated. Dense hydroxyapatite (HA),
      tricalcium phosphate (TCP), glassy carbon (GC), and 2 types of porous HA were
      used. Cutaneous and subcutaneous tissues were tightly attached to the surface of
      the penetrating portion of an HA percutaneous device (PD). Neither bacterial
      infection nor serious epidermal downgrowth were observed in the area surrounding
      the shaft of the HA-PD. At the margin of the epidermis, fibroblasts and collagen
      fibrils of fibrous connective tissue were well oriented and formed perpendicular
      to the shaft. The tissue response to the TCP was mild and nearly the same as that
      to the HA. The GC induced serious epidermal downgrowth and inflammatory cell
      infiltration. In contrast to dense HA-PD, the insertion of both types of porous
      HA-PDs, 1 with a spongy structure and 1 with close pores was followed by acute
      infection within 1 month. Based upon these results, it was concluded that the
      dense HA was the best percutaneous material of those tested.

PMID- 9288871
TI  - Characterization of modified alginate-poly-L-lysine microcapsules.
AB  - Various modifications of alginate-poly-L-lysine microcapsules were made, such as
      the inclusion of polyethylenimine (PEI) or carboxyl methyl cellulose (CMC) in the
      core and the coating of bis(polyoxyethylene bis[amine]) (PEGA) onto the
      microcapsule membrane surface. A characterization of the modified microcapsules
      in terms of mechanical and mass transfer properties as well as their chemical
      composition was performed. The PEI treatment greatly enhanced the mechanical
      stability of the microcapsules, and this treatment did not affect the coating
      process of poly-L-lysine or PEGA. PEGA was found to be able to coat the
      microcapsules while the mass transfer property was similar to the poly-L-lysine
      coated ones.

PMID- 9288873
TI  - Effects of tilting disk heart valve gap width on regurgitant flow through an
      artificial heart mitral valve.
AB  - While many investigators have measured the turbulent stresses associated with
      forward flow through tilting disk heart valves, only recently has attention been
      given to the regurgitant jets formed as fluid is squeezed through the gap between
      the occluder and housing of a closed valve. The objective of this investigation
      was to determine the effect of gap width on the turbulent stresses of the
      regurgitant jets through a Bjork-Shiley monostrut tilting disk heart valve seated
      in the mitral position of a Penn State artificial heart. A 2 component laser
      Doppler velocimetry system with a temporal resolution of 1 ms was used to measure
      the instantaneous velocities in the regurgitant jets in the major and minor
      orifices around the mitral valve. The gap width was controlled through
      temperature variation by taking advantage of the large difference between the
      thermal expansion coefficients of the Delrin occluder and the Stellite housing of
      Bjork-Shiley monostrut valves. The turbulent shear stress and mean (ensemble
      averaged) velocity were incorporated into a model of red blood cell damage to
      assess the potential for hemolytic damage at each gap width investigated. The
      results revealed that the minor orifice tends to form stronger jets during
      regurgitant flow than the major orifice, indicating that the gap width is not
      uniform around the circumference of the valve. Based on the results of a red
      blood cell damage model, the hemolytic potential of the mitral valve decreases as
      the gap width increases. This investigation also established that the hemolytic
      potential of the regurgitant phase of valve operation is comparable to, if not
      greater than, the hemolytic potential of forward flow, consistent with
      experimental data on hemolysis.

PMID- 9288872
TI  - Glutaraldehyde treated bovine pericardium: changes in calcification due to
      vitamins and platelet inhibitors.
AB  - Cardiovascular calcification, the formation of calcium phosphate deposits in
      cardiovascular tissue, is a common endstage phenomenon affecting a wide variety
      of bioprostheses. The purpose of the present paper is to study the possibility
      that some antiplatelet drugs (aspirin and persantine) and certain vitamins
      (vitamin C, vitamin B6, and vitamin E) and their combinations might prevent the
      mineralization of glutaraldehyde treated bovine pericardium (GABP) by modifying
      the pericardial surface. In this experimental protocol, we used Golomb and
      Wagner's (1991) in vitro model for studying GABP calcification and a diffusion
      cell with 2 compartments for evaluating the diffusion of calcium across the GABP.
      The results showed that a combination of aspirin and vitamins (0.5 mg% aspirin,
      1.5 mg% vitamin C, 4 mg% vitamin B6, and 2 mg% vitamin E) in a metastable calcium
      phosphate solution not only reduced the transport of calcium ions through GABP,
      but along with the combinations of 0.5 mg% aspirin and 5 mg% persantine also
      produced significant reductions in GABP calcification. The exact mechanism of
      these changes in the calcification of GABP are still unknown. From these in vitro
      findings, it appears that a combined vitamin therapy with low doses of aspirin
      may be beneficial for platelet suppression and thereby prevent thrombosis. In
      addition, the vitamins may modify calcium transport and interfere with the
      adsorption at the surface, thus reducing GABP calcification. However, an
      important question that remains unanswered is whether this inhibitory effect
      would continue if the antiplatelet drugs and vitamins were discontinued. For the
      answer, more in vivo studies are needed to develop applications.

PMID- 9288874
TI  - Development of a direct mechanical left ventricular assist device for left
      ventricular failure.
AB  - We have developed a direct mechanical left ventricular assist device (DMLVAD) for
      severe left ventricular failure. The DMLVAD was attached to the left ventricle
      and compressed the heart by a pneumatic driving unit. In a mock circulation model
      with an extracted nonbeating heart, a cardiac output (CO) of 1.93 L/min was
      obtained at a driving pressure of 200 mm Hg. In a canine left ventricular failure
      model induced by injection of sodium hydroxide into the myocardium, the systolic
      arterial pressure, systolic left ventricular pressure, maximum LV dP/dt, peak
      flow, and CO increased by 21, 24, 58, 144, and 37%, respectively. The mean left
      atrial pressure also decreased by 15% when the DMLVAD was driven. These effects
      were most prominent when the mean left atrial pressure was over 15 mm Hg, and the
      driving pressure was over 100 mm Hg. Compression at late systole was more
      effective in obtaining greater CO. We suggest that the DMLVAD could be an
      optional circulatory assist device for patients with left ventricular failure
      awaiting heart transplantation.

PMID- 9288875
TI  - Application of argatroban, direct thrombin inhibitor, in heparin-intolerant
      patients requiring extracorporeal circulation.
AB  - This study describes the present knowledge regarding the clinical application of
      argatroban, a direct competitive thrombin inhibitor for heparin-intolerant
      patients, including those with congenital and acquired antithrombin III
      deficiencies, those with heparin-induced thrombocytopenia, and those with high
      levels of polymorphonuclear granulocyte elastase. These patients are often
      associated with intracircuit clot formation with heparin anticoagulation during
      extracorporeal circulation. Therefore, argatroban may be chosen as one of the
      alternate anticoagulants. Because the anticoagulant effect of argatroban is
      reflected in the prolongation of activated thromboplastin time, monitoring is
      easy, similar to that for heparin. Because argatroban has a fast acting
      anticoagulant effect without any cofactors such as antithrombin III, this drug is
      a favorable anticoagulant for heparin-intolerant patients with antithrombin III
      deficiencies requiring extracorporeal circulation. In adverse reactions to
      heparin, heparin acts as an antigen after complexing with platelet factor 4,
      which leads to life-threatening heparin-induced thrombocytopenia. As argatroban
      prevents heparin-induced platelet aggregation, it is effective for use as a
      therapeutic anticoagulant. In other clinical applications, heparin decreases
      antithrombin activity and causes intracircuit clot formation during
      extracorporeal circulation when the polymorphonuclear granulocyte elastase level
      is very high. The antithrombin activity shows less decrease when argatroban is
      substituted for heparin. These findings indicate that argatroban is a useful
      alternative anticoagulant in these heparin-intolerant patients.

PMID- 9288876
TI  - Surface-treated catheters with ion beam-based process evaluation in rats.
AB  - Ion beam-based processes such as ion implantation (silicone rubber) and ion beam
      assisted deposition (silver-based coatings) affect the outer micron layers of
      catheter surfaces. These processes were used on the common catheter materials of
      silicone and polyurethane. In 56 rats, surface (Spi-Silicone and Spi-Argent I and
      II) catheter segments were implanted for 1, 3, and 6 weeks. After removal, these
      pieces were investigated for bacterial colonization and fixed for scanning
      electron microscopic evaluation. As controls, untreated catheter segments were
      implanted in 28 rats. Bacterial colonization was found in 2.4% in the surface
      treated catheter pieces versus 7.1% in the control group. The scanning electron
      microscope investigations showed low thrombogenicity in all of the treated
      catheters independent of the implantation times.

PMID- 9288877
TI  - Adsorption of basic fibroblast growth factor onto Dacron vascular prosthesis and
      its biological efficacy.
AB  - Adsorption of basic fibroblast growth factor (bFGF) onto a plain fabric Dacron
      vascular prosthesis (Micron, InterVascular Co., Ltd., Clearwater, FL, U.S.A.) and
      its release properties from the graft were examined using labeled bFGF, and its
      biological efficacy was evaluated in an animal study. In an in vitro study, 6
      pieces of a Dacron graft were soaked in [(125)I]-bFGF solution for 30 min. Then
      these pieces were soaked in 500 ml saline solution for 15 days, and the
      radioactivity of each piece was counted at various times. The initial amount of
      adsorbed bFGF was 2.48 ng/cm2. At 24 h, 41% of the adsorbed bFGF was released and
      59% remained. On the third day 55% remained, on the seventh day 52%, and on the
      15th day 50% remained on the Dacron surface. Using the atmospheric glow discharge
      (APG) plasma treatment to render hydrophilic properties, no significant
      difference between plasma-treated grafts and non-plasma-treated grafts regarding
      the adsorption of bFGF was observed. In an in vivo study, 6 Dacron pieces
      adsorbed with bFGF were implanted in the subcutaneous layer of 2 dogs and removed
      5 days after implantation. Six Dacron pieces without bFGF were also implanted as
      a control into the 2 dogs. Fibroblast migration with capillary ingrowth was
      observed in the specimens with bFGF compared to the controls. These results
      indicate that the simple adsorption of bFGF onto Dacron fabric is a useful method
      for the acceleration of host cell migration and capillary ingrowth into Dacron
      fabric vascular prostheses.

PMID- 9288879
TI  - The influence of the Product Liability Act, governmental regulation, and medical
      economics on medical devices and their clinical applications.

PMID- 9288878
TI  - Single lead atrial synchronous ventricular pacing in Japanese patients with
      complete atrioventricular block.
AB  - The purpose of this study was to review our experience with atrial synchronous
      ventricular pacing devices (THERA VDD pacing systems, Medtronic, Inc., U.S.A.)
      using single atrioventricular leads in Japanese patients with complete
      atrioventricular block and normal sinus function. Twenty patients with a mean age
      of 55 +/- 13 years underwent implantation of VDD pacemakers. At implantation the
      amplitude of atrial signals in the supine position during normal breathing, which
      was measured directly using an external pacing system analyzer, ranged from 1.8
      to 5.8 mV with a mean amplitude of 3.4 +/- 1.4 mV. Atrial amplitudes did not
      change during deep breathing (3.3 +/- 1.1 mV) or in the semi-Fowler position (3.4
      +/- 1.6 mV). Atrial oversensing or undersensing was not observed in any of the
      patients. During a follow-up period, the percentage of atrial synchronization was
      >95% in 19 patients, and none of the patients had pacemaker related tachycardia
      or pacemaker related complications. These results were promising enough to
      warrant the extension of the clinical use of the VDD pacemaker.

PMID- 9288880
TI  - Detection of DNA modifications by the 32P-postlabelling assay.
AB  - The 32P-postlabelling assay is widely used for detection of carcinogen-DNA
      adducts and other types of modified nucleotides in DNA. The principle of the
      method is the enzymatic digestion of DNA to nucleotides, 5'-labelling of these
      nucleotides with an isotopically labelled phosphate group, and the resolution and
      detection of the labelled products. Since the development of the original
      procedure in the early 1980s, many methods have been developed to increase the
      sensitivity of the method by selection of the modified nucleotides prior to
      labelling. In favourable circumstances, the method can achieve a level of
      detection as low as 1 modification in 10(10) nucleotides and requires relatively
      small quantities of DNA (less than 10 microg). It has been used to detect and
      characterise DNA adducts formed by numerous genotoxic carcinogens in bacterial
      and mammalian cells, in animals and, in some cases, in human tissues. Most
      classes of carcinogen have been subjected to 32P-postlabelling analysis, ranging
      from bulky and/or aromatic compounds to small and/or aliphatic compounds; it has
      also been used, with modifications, to detect apurinic sites in DNA, oxidative
      damage to DNA, UV-induced photodimers and, to a lesser extent, DNA damage caused
      by cytotoxic drugs. It has provided the first clear evidence for the DNA-damaging
      properties of several synthetic carcinogenic hormones. It has revealed the DNA
      damaging potential of complex mixtures such as coal-tar and tobacco smoke. It has
      been used in human biomonitoring studies to detect DNA damage from occupational
      exposure to carcinogens, and also from environmental (i.e. non-occupational)
      exposures. It has also led to the discovery of the presence of numerous
      modifications in DNA arising from endogenous processes. The rapid expansion in
      the use of the assay has resulted in some divergence of procedures and there is a
      case to be made for the use of more standardised protocols, particularly where
      human exposure to carcinogens is being measured and where such results may be
      required for risk assessment. While the procedure is quantifiable, the efficiency
      of adduct labelling is, in many cases, not quantitative, and the lack of adduct
      standards has, in many cases, limited the interpretation of data to a
      demonstration of higher adduct levels in exposed groups compared with unexposed
      groups. Future developments are expected in automation, standardisation and, in
      combination with other analytical methods, elucidation of the structures of the
      many DNA lesions whose existence has been revealed by the 32P-postlabelling
      technique.

PMID- 9288881
TI  - Pancreatic DNA adducts formed in vitro and in vivo by the food mutagens 2-amino-1
      methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3-methyl-9H-pyrido[2,3
      b]indole (MeA alphaC).
AB  - Genotoxic heterocyclic amines have been detected in grilled or fried meat and
      tobacco smoke. Among these, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      (PhIP) and 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alphaC) have been shown
      to induce tumours in rodents in several organs. Here we report on the DNA adduct
      formation by PhIP and MeA alphaC in vitro and in vivo, both in rat hepatic and
      rat pancreatic tissues or cells. Using 32P-postlabelling analysis both compounds
      were shown to induce a dose-dependent DNA modification in primary rat hepatocytes
      that was correlated with cytotoxicity in these cells. In explanted rat pancreas
      maintained in dynamic short-term organ culture MeA alphaC was shown to induce
      covalent DNA adducts. No DNA adducts were observed with PhIP in this assay. DNA
      adducts were observed in the liver and the pancreas of F344 rats treated with
      PhIP, with a 36-times higher level of adducts in the pancreas, confirming data
      reported earlier. DNA adduct levels induced by feeding 32, 160 or 800 ppm MeA
      alphaC in the diet were dose-dependent and higher in the liver compared with
      other organs including pancreas. While for PhIP the N2-(desoxyguanin-8-yl)
      derivative was accounting for more than 90% of DNA adducts detected, in the case
      of MeA alphaC the N2-(desoxyguanin-8-yl) adduct was predominant in vitro and
      determined in vivo as one of up to 5 DNA adducts. MeA alphaC had been reported to
      induce preneoplastic foci and tumours in the liver and tumours and atrophy in the
      pancreas. In the case of MeA alphaC, the DNA adduct formation and cytotoxicity
      observed by us in vitro and in vivo correlate with the organ specificity of the
      reported pathological lesions. In the case of PhIP our in vitro data in pancreas
      and liver and the low adduct levels in liver in vivo also reflect the reported
      lack of pathological effects in these organs. In contrast, in pancreas, in vivo
      extraordinarily high adduct levels induced by PhIP were observed confirming
      studies published earlier, in spite of the fact that this compound does not cause
      pancreatic lesions. This enigmatic observation is discussed and the relevant
      literature is reviewed.

PMID- 9288882
TI  - Formation and persistence of DNA adducts of 2-amino-3-methylimidazo[4,5
      f]quinoline (IQ) in CDF1 mice fed a high omega-3 fatty acid diet.
AB  - The potent bacterial mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is
      carcinogenic in the CDF1 mouse, affecting the liver, lungs and forestomach. IQ
      forms DNA adducts in both target- and non-target organs of the CDF1 mouse. The
      chemopreventive effects of menhaden oil (MO), a fish oil high in omega-3 fatty
      acids, are well known. Because DNA adduct formation is considered to be a
      critical event in the initiation of carcinogenesis, we have assessed the effects
      of dietary MO on IQ-DNA adduct formation. For the duration of the study, young
      adult, male CDF1 mice were maintained on either powdered chow diet, AIN-76A diet,
      or AIN-76A diet modified to contain 19% MO (19% MO diet). After 2 weeks on these
      diets, all animals received 0.01% (w/w) IQ in the diet for the next 3 weeks.
      Groups of 4 animals were killed 1, 2, 4, 6, 8 or 12 days thereafter for analysis
      of IQ-DNA adducts by 32P-postlabeling. IQ-DNA adduct patterns were qualitatively
      similar in the liver, lungs, stomach, small intestine, cecum, colon, kidneys,
      heart and spleen. Adduct levels in the liver, lungs, stomach and colon decreased
      significantly during the 12-day study period, but only to a relatively small
      extent and only with certain of the diets. On day 1, the 19% MO diet
      significantly decreased (35.8-90.0%) adduct levels in the stomach, cecum, colon
      and kidneys, when compared to chow diet or AIN-76A diet. On day 12, adduct levels
      in the liver, stomach, heart and spleen were decreased (36.5-64.7%) as a result
      of MO feeding. With the exception of the liver, heart and spleen on day 12, there
      were no significant differences in organ adduct levels between the chow diet and
      the AIN-76A diet. It is concluded that feeding 0.01% (w/w) IQ in the diet for 3
      weeks results in a relatively slow rate of adduct removal and that this rate is
      largely independent of the type of diet. Dietary MO inhibits IQ-DNA adduct
      formation only in certain target- and non-target organs of the CDF1 mouse, a
      finding similar to our previous results in the F344 rat. MO may affect the
      initiation phase of IQ tumorigenesis by inhibiting IQ-DNA adduct formation in
      certain target organs.

PMID- 9288884
TI  - The use of benzo[a]pyrene diolepoxide-modified DNA standards for adduct
      quantification in 32P-postlabelling to assess exposure to polycyclic aromatic
      hydrocarbons: application in a biomonitoring study.
AB  - The 32P-postlabelling assay is one of the most sensitive methods for detection of
      DNA adducts induced by exposure to genotoxic chemicals. Under optimal conditions,
      detection limits of one adduct per 10(9)-10(10) nucleotides have been reported.
      This sensitivity now allows monitoring of occupational and even environmental
      exposure of humans to certain classes of chemicals, mainly polycyclic aromatic
      hydrocarbons (PAH). Despite its widespread use, 3P-postlabelling is still not a
      standardized method. Rigorous interlaboratory comparisons are scarce, and those
      that have been undertaken often show rather different results, both in relative
      and in absolute values, for the amounts of DNA adducts in the same samples.
      Furthermore, the optimization of many steps in the procedure has still not been
      given adequate attention. This paper deals with some technical aspects of
      detection of PAH-DNA adducts by 32P-postlabelling, in particular with assay
      calibration and adduct quantification. For this purpose, benzo[a]pyrene (BP)
      modified DNA standards were prepared, the adduct contents of which were
      determined by use of an independent fluorometric method, viz. synchronous
      fluorescence spectrophotometry (SFS). These BP-DNA standards are processed along
      with the test samples throughout the entire 32P-postlabelling procedure, from the
      enzymic digestion up to and including the determination of radioactivity in
      adduct spots on the chromatogram. As such, these reference samples can be
      considered as external standards for inter-assay calibration. This method for
      adduct quantification was compared with the commonly used relative adduct
      labelling (RAL) and comparative dAMP labelling, which appeared to give rise to an
      underestimation of adduct levels. The method was applied in a biomonitoring study
      among workers in a carbon-electrode manufacturing plant, exposed to PAH. Although
      DNA adduct levels in peripheral blood lymphocytes of exposed workers, as
      determined by 32P-postlabelling, were not significantly different from those of
      controls, a significant difference was seen when smokers and non-smokers were
      compared.

PMID- 9288883
TI  - Tissue distribution of DNA adducts in rats treated by intramammillary injection
      with dibenzo[a,l]pyrene, 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene.
AB  - Dibenzo[a,l]pyrene (DBP) has recently emerged as a potent environmental
      carcinogen having greater carcinogenicity in the rat mammary epithelial glands
      than 7,12-dimethylbenz[a]anthracene (DMBA), previously considered to be the most
      potent mammary carcinogen and benzo[a]pyrene (BP), a ubiquitous environmental
      carcinogen. Previous studies on the tumor-initiating potential of DBP, DMBA, and
      BP demonstrated that DBP was 2.5 times more potent in inducing the tumors in
      mouse skin and rat mammary glands than DMBA; BP was a weak mammary carcinogen in
      these animals. The present study was designed to investigate if the significantly
      increased mammary carcinogenicity of DBP over DMBA and BP was related to
      increased DNA adduction at the target site. Female Sprague-Dawley rats were
      treated by intramammillary injection with an equimolar dose of 0.25
      micromol/gland of DBP, DMBA, and BP at the 3rd, 4th and 5th mammary glands on
      both sides. 32P-Postlabeling analysis of mammary epithelial DNA of rats treated
      with DBP produced two major (nos. 3 and 6) and at least 5 minor adducts. DMBA
      treatment resulted in one major and 4 minor DNA adducts while BP produced one
      major and two minor adducts. Quantitation of the adduct radioactivity revealed
      that DNA adduction was 6- and 9-fold greater in DBP-treated animals than in BP-
      and DMBA-treated animals, respectively. The adduct levels per 10(9) nucleotides
      in mammary epithelial cells for DBP, BP and DMBA were in the following descending
      order: 1828 +/- 378, 300 +/- 45 and 207 +/- 72, respectively. Tissue distribution
      of DNA adducts in non-target organs following DBP treatment showed similar adduct
      pattern as found in the mammary epithelial cells except the liver, which resulted
      in 4 additional adduct spots; vehicle-treated tissue DNA processed in parallel
      did not show any detectable adducts. DMBA- and BP-DNA adduct patterns in various
      tissues were similar to that found in mammary epithelial cells, however,
      significant quantitative differences were found; BP-DNA adducts were undetectable
      in the pancreas and bladder. Quantitation of adduct radioactivity showed a 15- to
      60-fold lower DBP-DNA adduction in these tissues than the levels found in the
      mammary tissue; similarly 5-20 and 30-100 times lower DNA adduction was found
      following treatment with DMBA and BP, respectively. The significantly increased
      binding of DBP to the mammary epithelial DNA over BP and DMBA is in concordance
      with its known higher mutagenicity and tumorigenicity.

PMID- 9288885
TI  - Air pollution exposure-DNA adduct dosimetry in humans and rodents: evidence for
      non-linearity at high doses.
AB  - The impact of air pollution exposure on the level of total DNA adducts in human
      white blood cells (WBCs) was evaluated in two populations in the Czech Republic
      and compared to the exposure-DNA adduct relationship in other populations in the
      US and China in human lung cells and rodent lung tissue. The human populations
      examined were exposed to respirable particles (< 2.5 microm) (PM2.5) in urban,
      rural, and occupational settings where the particles originated from coal and
      petroleum fuel combustion, coke production, and other coal-tar aerosols (e.g.,
      used in aluminum production). These particles contain carcinogenic polycyclic
      aromatic hydrocarbons (PAHs) that are known to form DNA adducts through covalent
      binding. Personal exposure to PM2.5 and PAHs were measured prior to collection of
      blood samples for DNA adduct analysis by 32P-postlabeling. Coke oven workers (n =
      76), in 10 job categories on the top and side of a coke oven in Ostrava, CZ, were
      studied and compared to a different population exposed to environmental levels of
      PAHs from air pollution in Teplice, CZ. Personal exposures to airborne particles
      ranged from < 1 to more than 15,000 microg/m3 and carcinogenic PAHs exposure
      ranged from < 5 to > 200,000 ng/m3. At low to moderate environmental exposures to
      carcinogenic PAHs, DNA adduct levels in the WBCs were significantly correlated
      with exposure. However, at the higher occupational levels found on the coke oven,
      the exposure-DNA adduct relationship became non-linear. Under these high exposure
      conditions, the relative DNA adduct level per unit of exposure (DNA-binding
      potency) was significantly lower than measured at environmental exposures. This
      finding is consistent with observations in lung cells from bronchoalveolar lavage
      of humans exposed to a wide range of PAH. This same high exposure-dose non
      linearity was also observed in lung DNA from rats exposed by inhalation to a coal
      tar pitch aerosol. DNA adduct levels in all these cases show evidence of a form
      of non-linearity at high doses that has been described by Lutz (W.K. Lutz, Dose
      response relationship and low dose extrapolation in chemical carcinogenesis,
      Carcinogenesis, 11 (1990) 1243-1247) as a superlinear dose response. This
      superlinear response may be due to saturation of metabolic activation enzymes,
      induction of either DNA repair processes or detoxification enzymes, or other
      mechanisms. Regardless of the mechanism, this decrease in the DNA-binding potency
      at moderate to high doses of PAH has important implications for dose-response
      extrapolation in risk assessment.

PMID- 9288886
TI  - 32P-postlabelling of aromatic DNA adducts in white blood cells and alveolar
      macrophages of smokers: saturation at high exposures.
AB  - DNA adducts may serve as a molecular dosimeter of exposure to cigarette smoke
      associated carcinogens such as polycyclic aromatic hydrocarbons (PAH). Target
      tissues for cigarette smoke-induced carcinogenesis are rarely accessible;
      therefore, peripheral blood cells or cells obtained by bronchoalveolar lavage
      (BAL) may be used as surrogate sources of exposed DNA. However, the relationship
      between cigarette smoke exposure and aromatic-DNA adducts in white blood cells
      and BAL cells is still unclear. In this study, we examined DNA adduct formation
      in lymphocytes and BAL cells in several populations of smoking individuals by
      means of 32P-postlabelling. Significant correlations between the amount of
      cigarettes smoked per day and the level of aromatic-DNA adducts were found in
      lymphocytes. In BAL cells, DNA adduct levels were associated with age (p = 0.05)
      and gender (p = 0.10) after adjustment for smoking behaviour. Adduct formation
      levelled off at higher exposure levels, suggesting less efficient adduct
      formation; decreases in the formation of adducts per unit of exposure were found
      in lymphocytes (r(s) = -0.80, p < 0.001) and BAL cells (r(s) = -0.72, p < 0.001).
      To assess intra-individual variation in adduct levels at constant smoking
      behaviour, sampling was repeated after a period of 2 and 6 months. In
      lymphocytes, repeated measurements with an interval of 2 months were highly
      correlated (r = 0.84, p = 0.009, n = 8), whereas repeated measurements with an
      interval of 6 months showed no correlation (r = 0.30, p = 0.27, n = 16). Repeated
      measurements in BAL cells showed a significant correlation after 6 months (r =
      0.68, p = 0.03, n = 10). Furthermore, in a group of occupationally exposed
      aluminium workers, adduct levels in total white blood cells were correlated with
      the average concentrations of PAH in the ambient air of workers who smoked
      cigarettes, whereas in non-smokers, no such relationship was found. We conclude
      that cigarette smoking may directly or indirectly influence DNA adduct levels and
      saturation of DNA adduct formation may occur, leading to non-linear dose-response
      relationships.

PMID- 9288887
TI  - The application of the 32P-postlabelling assay to aquatic biomonitoring.
AB  - The aquatic environment is known to contain a variety of natural and
      anthropogenic compounds that are capable of interacting with the genetic material
      of aquatic organisms. The increases in the levels of these anthropogenic
      contaminants, associated with widespread industrialisation, has led to the
      requirement for reliable methodologies to monitor their potential impact upon
      exposed aquatic organisms. Of the molecular techniques currently available, the
      32P-postlabelling assay for the detection of DNA adducts offers considerable
      potential for the qualitative and quantitative assessment of genotoxin exposure.
      Here we describe several studies in which the technique was adapted for
      evaluation in two marine bioindicator species the common mussel Mytilus edulis
      and the flatfish Limanda limanda. Laboratory studies in which M. edulis specimens
      were exposed to 2-aminofluorene and 4-nitroquinoline 1-oxide confirmed the
      species' capacity to form genotoxin-related adducts. However, in further studies,
      no exposure-related adducts could be detected in M. edulis specimens placed in
      mesocosms containing environmentally realistic levels of anthropogenic
      contaminants. Biologically significant levels of adducts were detected in L.
      limanda specimens exposed to sediment bound contaminants under controlled
      conditions, although the levels did not appear to be statistically significant.
      An in situ study in which adduct levels were determined in L. limanda specimens
      from two sites of contrasting contamination levels proved to be more conclusive.
      The results were both biologically and statistically significant, suggesting that
      adduct levels could well be related to the levels of sediment-bound contaminants.
      Together the studies confirmed that the determination of the levels of DNA
      adducts could be used as indicators of the exposure of aquatic organisms to
      environmental genotoxins.

PMID- 9288888
TI  - Correlation of mutagenic potencies of various petroleum oils and oil coal tar
      mixtures with DNA adduct levels in vitro.
AB  - An in vitro system was utilized to measure DNA adduct-forming ability of
      petroleum oils and oil coal tar mixtures to define correlations between DNA
      adduct levels and their mutagenic potencies. The system consisted of reaction of
      dimethyl sulfoxide extracts of oils with calf thymus DNA in the presence of
      Aroclor-induced hamster liver microsomes for 30 min. Following DNA extraction,
      DNA adducts were measured by the nuclease P1-enhanced postlabeling assay coupled
      with two-dimensional polyethyleneimine (PEI)-cellulose TLC. Thin layer plates
      showed putative aromatic DNA adducts, with levels ranging from 60 to 1400 adducts
      per 10(9) DNA nucleotides. TLC mobilities suggested adducts to be aromatic
      compounds containing 4 or more rings. A good correlation (coefficient of
      correlation = 0.91) was observed between DNA adduct levels and Salmonella
      mutagenicity for 19 oils. All 19 samples tested produced DNA adducts. To expedite
      the TLC procedure, adducts were resolved by one-dimensional TLC and the
      radioactivity measured using a mechanical scanner. Results were comparable to
      those obtained by two-dimensional TLC and quantification after scraping. Our data
      show that the in vitro incubation system coupled with the postlabeling adduct
      assay is a useful screening method to identify mutagenic and potentially
      carcinogenic oils.

PMID- 9288889
TI  - Immunochemical, 32P-postlabeling, and GC/MS detection of 4-aminobiphenyl-DNA
      adducts in human peripheral lung in relation to metabolic activation pathways
      involving pulmonary N-oxidation, conjugation, and peroxidation.
AB  - 4-Aminobiphenyl (ABP) is a recognized human bladder carcinogen, whose presence in
      cigarette smoke results in DNA adduct formation in the human urothelium. Since
      preliminary studies indicated that even higher levels of ABP-DNA adducts may be
      present in human peripheral lung, we utilized a sensitive immunochemical assay,
      in combination with 32P-postlabeling, to quantify the major 4-aminobiphenyl (ABP)
      DNA adduct, N-(guan-8-yl)-ABP, in surgical samples of peripheral lung tissue from
      smokers and ex-smokers. No differences in adduct levels were detected between
      smokers and ex-smokers by immunoassay. In contrast, the 32P-postlabeling method
      showed statistically significant differences between adduct levels in smokers and
      ex-smokers; however, a relatively high background of smoking-related adducts
      chromatograph near the major ABP adducts and may compromise estimation of the
      level of ABP-DNA adducts in smokers. Furthermore, the levels measured by 32P
      postlabeling were 20- to 60-fold lower than that measured by immunoassay. Since
      32P-postlabeling may underestimate and immunochemical assays may overestimate
      adduct levels in the lung, selected samples were also evaluated by GC/MS. The
      immunochemical and GC/MS data were concordant, leading us to conclude that N
      (guan-8-yl)-ABP adducts were not related to smoking status. Since ABP-DNA adduct
      levels in human lung did not correlate with smoking status as measured by
      immunoassay and GC/MS, the metabolic activation capacity of human lung microsomes
      and cytosols was examined to determine if another exposure (e.g., 4
      nitrobiphenyl) might be responsible for the adduct. The rates of microsomal ABP N
      oxidation were below the limit of detection, which was consistent with a lack of
      detectable cytochrome P4501A2 in human lung. N-Hydroxy-ABP O-acetyltransferase
      (but not sulfotransferase) activity was detected in cytosols and comparative
      measurements of N-acetyltransferase (NAT) using p-aminobenzoic acid and
      sulfamethazine indicated that NAT1 and NAT2 contributed to this activity. 4
      Nitrobiphenyl reductase activity was found in lung microsomes and cytosols, with
      the reaction yielding ABP and N-hydroxy-ABP. Lung microsomes also demonstrated
      high peroxidative activation of ABP, benzidine, 4,4'-methylene-bis(2
      chloroaniline), 2-aminofluorene, and 2-naphthylamine. The preferred co-oxidant
      was hydrogen peroxide and the reaction was strongly inhibited by sodium azide but
      not by indomethacin or eicosatetraynoic acid, which suggested the primary
      involvement of myeloperoxidase rather than prostaglandin H synthase or
      lipoxygenase. This was confirmed by immunoinhibition and immunoprecipitation
      studies using solubilized human lung microsomes and antisera specific for
      myeloperoxidase. These data suggest that ABP-DNA adducts in human lung result
      from some environmental exposure to 4-nitrobiphenyl. The bioactivation pathways
      appear to involve: (1) metabolic reduction to N-hydroxy-ABP and subsequent O
      acetylation by NAT1 and/or NAT2; and (2) metabolic reduction to ABP and
      subsequent peroxidation by myeloperoxidase. The myeloperoxidase activity appears
      to be the highest peroxidase activity measured in mammalian tissue and is
      consistent with the presence of neutrophils and polymorphonuclear leukocytes
      surrounding particulate matter derived from cigarette smoking.

PMID- 9288890
TI  - The use of 32P-postlabelling in studies of the nature and origin of DNA adducts
      formed by bile from patients with familial adenomatous polyposis and from normal
      patients.
AB  - 32P-postlabelling is a highly sensitive technique for the detection of DNA
      adducts. It is unique in that it requires no prior knowledge of the nature of
      adducts or adduct-forming species under investigation. In the past, we have used
      this technique to investigate the role of bile in the production of foregut
      adenomas in patients with familial adenomatous polyposis (FAP). We have found
      that bile contains constituents that form DNA adducts directly, and after
      metabolic activation, and that the bile of FAP patients has an increased capacity
      for adduct formation with DNA in vitro, in human cell lines in culture, and in
      the gastrointestinal tract of rats given bile by gavage. The sensitivity of 32P
      postlabelling is such that it is difficult to obtain sufficient quantities of DNA
      adducts for chemical analysis. The nature of the adducts produced by bile, or of
      the bile constituents that produce them is as yet undetermined. In the present
      studies, we have combined 32P-postlabelling with indirect methods to gain some
      insight into the nature of DNA adducts produced by bile and the properties of the
      reactive species that form them. Firstly, bile was incubated with synthetic
      monodeoxynucleotides or polydeoxynucleotides. Bile did not produce adducts when
      incubated with monodeoxynucleotides or single-stranded polydeoxynucleotides.
      However, it did produce adducts when incubated with double-stranded
      polydeoxynucleotides. The pattern of adduct formation suggested that human bile
      forms a mixture of adenine and guanine adducts. Secondly, bile was fractionated
      by extraction with blue cotton or with neutral, acid or alkaline organic solvent.
      Blue cotton, which efficiently and selectively absorbs mutagens having 3 or more
      fused aromatic rings, did not absorb biliary constituents that could form adducts
      with DNA in vitro or with DNA of MCL-5 cells, a metabolically competent human
      cell line. This suggests that biliary DNA adduct precursors are polar compounds
      that contain fewer than 3 aromatic rings or are non-aromatic. Acidic organic
      extracts of human bile produced much higher levels of DNA adducts in vitro or
      with DNA of MCL-5 cells than did neutral or alkaline organic extracts, suggesting
      that constituents of bile that form DNA adducts are acidic in nature.

PMID- 9288891
TI  - Use of a postlabelling assay to examine the removal of radiation-induced DNA
      lesions by purified enzymes and human cell extracts.
AB  - We have used a 32P-postlabelling assay to examine the activity of purified
      Esherichia coli endonuclease IV, human apurinic/apyrimidinic endonuclease I and
      human cell-free extracts towards irradiated DNA. The assay can detect thymine
      glycols, 3'-phosphoglycolate groups and at least one other major lesion that has
      yet to be fully characterized. It was observed that endonuclease IV removed the
      phosphoglycolates and the uncharacterized lesion(s) suggesting that the latter
      are abasic sites with modified deoxyribose residues. The purified human enzyme
      acted only on the phosphoglycolate residues. Cell-free extract, prepared from
      A549 lung carcinoma cells by sonication or treatment with toluene, efficiently
      removed the phosphoglycolate and unknown lesions, but was less reactive towards
      thymine glycols. The extract was completely inactivated by heating at 60 degrees
      C for 10 min. Removal of the unknown product and phosphoglycolate did not require
      magnesium, but 1 mM EDTA did inhibit release of the latter. The cell-free extract
      exhibited substantially more activity towards native than heat-denatured DNA. A
      comparison of extracts prepared from 4 cell lines displaying a range of
      radiosensitivities, including an ataxia telangiectasia cell line, showed that all
      contained similar levels of repair activity towards the detectable lesions.

PMID- 9288893
TI  - Self-cleaving ribozymes of hepatitis delta virus RNA.
AB  - Hepatitis delta virus (HDV) is a small single-stranded RNA satellite of hepatitis
      B virus. Although it is a human pathogen, it shares a number of features with a
      subset of the small plant satellite RNA viruses, including self-cleaving
      sequences in the genomic and antigenomic sequences of the viral RNA. The self
      cleaving sequence is critical to viral replication and is thought to function as
      a ribozyme in vivo to process the products of rolling-circle replication to unit
      length molecules. A divalent cation is required for cleavage and while a
      structural role is implicated for metal ions, a more direct role for a metal ion
      in catalysis has not yet been proven. A minimal natural ribozyme sequence with
      proficient in vitro self-cleavage activity is about 85 nucleotides long and
      adopts a secondary structure with four paired regions (P1-P4). The two pairings
      that define the 5' and 3' boundaries of the ribozyme, P1 and P2, form an atypical
      pseudoknot arrangement. This secondary structure places a number of constraints
      on the possible tertiary folding of the sequence, which together with chemical
      probing, photo-cross-linking, mutagenesis and computer-assisted modeling provides
      clues to the three-dimensional structure. The data are consistent with a model in
      which the cleavage site, located at the 5' end of P1, is in close proximity to
      three single-stranded regions, consisting of a hairpin loop at the end of P3 and
      two sequences joining P1 to P4 and P4 to P2. While the natural forms of the HDV
      ribozymes appear to be prone to misfolding, biochemical and mutagenesis studies
      from a number of laboratories has allowed the production of trans-acting
      ribozymes and smaller more active cis-acting ribozymes, both of which will aid in
      further mechanistic and structural studies of this RNA.

PMID- 9288892
TI  - 32P-postlabelling approaches for the detection of 8-oxo-2'-deoxyguanosine-3'
      monophosphate in DNA.
AB  - 32P-Postlabelling methods have been investigated for the analysis of the
      oxidative DNA damage lesion 8-oxoguanine. The extent of digestion of commercially
      available calf thymus DNA and an 8-oxo-2'-deoxyguanosine-3'-monophosphate
      (8oxodGp) containing oligonucleotide to 2'-deoxynucleotide-3'-monophosphates,
      using calf spleen phosphodiesterase and micrococcal nuclease, was determined by
      HPLC. The extent of unmodified nucleotide release from DNA, and the extent of
      8oxodGp released from the oligomer did not increase between 1 and 16 h of
      incubation at 37 degrees C. Normal nucleotide release from DNA was found to be
      quantitative under these conditions, and 8oxodGp release from the oligomer was in
      the range of 84-91%. RNA contamination in DNA prepared for 32P-postlabelling
      severely compromised 8oxodGp analysis. Guanosine-3'-monophosphate (Gp) was found
      to exhibit similar chromatographic and electrophoretic properties to 8oxodGp and
      as such compromised both 8oxodGp isolation in enrichment steps and subsequent
      resolution of the 32P-labelled bisnucleotides by TLC. The effect of ribonuclease
      A, T1 and T2 was investigated and a combination of A + T1 was found to reduce Gp
      contamination in DNA samples to levels which no longer interfered with 8oxodGp
      analysis. We have successfully applied an HPLC enrichment protocol to the
      analysis of 8oxodGp in calf thymus DNA. Since determination of damage levels in
      human samples is often restricted by the amount of DNA available for analysis, a
      novel capillary electrophoresis (CE) technique for the enrichment of 8oxodGp has
      been developed. The advantage of CE is that it can achieve resolution of 8oxodGp
      and unmodified deoxynucleotides from much smaller samples and minimises the
      amount of [gamma-32P]ATP necessary for the analysis.

PMID- 9288894
TI  - Binding kinetics of Bacillus sphaericus binary toxin to midgut brush-border
      membranes of Anopheles and Culex sp. mosquito larvae.
AB  - Direct-binding assays and homologous-competition assays were used to identify
      specific binding between the radiolabelled toxin of Bacillus sphaericus and brush
      border membrane fractions (BBMF) from Anopheles gambiae and Anopheles stephensi,
      obtained from whole larvae preparations. In both species, the toxin bound to a
      single class of receptors. BBMF of A. gambiae had the highest binding affinity
      for the toxin of the species tested, with a dissociation constant (Kd) of 30 +/-
      15 nM and a maximum receptor concentration of 5 +/- 1 pmol/mg. Toxin binding to
      A. gambiae BBMF was compared with that to BBMF from B. sphaericus-susceptible
      (IP) and B. sphaericus-resistant (SPHAE) Culex pipiens populations. BBMF toxin
      binding was slower in A. gambiae than in the C. pipiens populations. The BBMF of
      the B. sphaericus-resistant population of C. pipiens had an association profile
      that was similar to the susceptible population, despite of the lack of
      susceptibility in vivo. No relationship between toxicity and irreversibility of
      toxin binding was detected. On the contrary, toxin dissociation from BBMF was
      fast and almost complete in BBMF of all species studied.

PMID- 9288895
TI  - Identification of an adenine-nucleotide-binding site on interferon alpha2.
AB  - Using 32P-labeled 2-azidoadenosine 5'-triphosphate (2N3ATP) and 8-azidoadenosine
      5'-triphosphate (8N3ATP), we have identified a site on human interferon alpha2
      (IFN-alpha2) that binds adenine nucleotides. The results from saturation and
      competition experiments demonstrated the specificity of the nucleotide
      interaction. Half-maximal saturation of IFN-alpha2 was observed at 10 microM
      2N3ATP or 35 microM 8N3ATP. ATP effectively decreased photoinsertion of both
      photoaffinity analogs of ATP. Photoinsertion of 8N3ATP was enhanced by MgCl2,
      independent of the ionic strength, and exhibited an optimum pH between 7.0 and
      7.5. Immobilized-Al3+ affinity chromatography and HPLC were used to purify the
      modified peptides from IFN-alpha2 that had been photolabeled with 8N3ATP and
      digested with trypsin or chymotrypsin. Overlapping-sequence analysis localized
      the sites of photoinsertion to the region corresponding to Lys121-Tyr135 in the
      amino acid sequence of IFN-alpha2, which almost perfectly overlaps a nuclear
      localization signal (R120KYFQRITLYLKEKKY135).

PMID- 9288896
TI  - Oligomeric states and siderophore binding of the ligand-gated FhuA protein that
      forms channels across Escherichia coli outer membranes.
AB  - The channel-forming FhuA protein, which translocates ferrichrome across
      Escherichia coli outer membranes, binds 1 mol ligand/mol monomer in detergent
      solution. The protein is homogenous and migrates as a single band with a mobility
      corresponding to 77 kDa in SDS/PAGE electrophoresis. Analytical
      ultracentrifugation revealed a monodisperse species (s(20,w) = 3.8 S) with a mass
      of 77,800 +/- 3200 Da. The properties of ligand binding, determined by two
      independent methods, revealed one binding site/monomer, but are complicated by a
      pronounced convexity of the Scatchard plot and a Hill coefficient calculated to
      be 2.5. This strongly suggests that oligomeric species are present. Cross-linking
      agents revealed the existence of possibly transient, mostly dimeric and trimeric
      species. The difference between the FhuA protein in detergent solution and in its
      native membrane environment may be related to the removal of lateral pressure
      that exists in situ.

PMID- 9288897
TI  - A heterodimer of the Zn2Cys6 transcription factors Pip2p and Oaf1p controls
      induction of genes encoding peroxisomal proteins in Saccharomyces cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, two transcriptional activators belonging
      to the Zn2Cys6 protein family, Pip2p and Oaf1p, are involved in fatty-acid
      dependent induction of genes encoding peroxisomal proteins. This induction is
      mediated via an upstream activation sequence called the oleate-response element
      (ORE). DNA-bandshift experiments with ORE probes and epitope-tagged proteins
      showed that two binary complexes occurred: in wild-type cells the major complex
      consisted of a Pip2p x Oaf1p heterodimer, but in cells in which Oaf1p was
      overexpressed an Oaf1p homodimer was also observed. The genes encoding Oaf1p and
      Pip2p were controlled in different ways. The OAF1 gene was constitutively
      expressed, while the PIP2 gene was induced upon growth on oleate, giving rise to
      positive autoregulatory control. We have shown that the Pip2p x Oaf1p heterodimer
      is responsible for the strong expression of the genes encoding peroxisomal
      proteins upon growth on oleate. Pip2p and Oaf1p form an example of a heterodimere
      of yeast Zn2Cys6 zinc-finger proteins binding to DNA.

PMID- 9288898
TI  - Isolation and amino acid sequence analysis reveal an ancient evolutionary origin
      of the cleavage stage (CS) histones of the sea urchin.
AB  - The cleavage stage (CS) H1, H2A, and H2B histones of the sea urchin, which have
      previously been identified by their distinct electrophoretic mobility on
      Triton/acid/urea gels, are known to be maternally expressed during oogenesis and
      have been implicated in chromatin remodeling of the male pronucleus following
      fertilization. Here, we describe the isolation of these three CS histones by
      reverse-phase HPLC chromatography. Moreover, a novel CS H3 protein was identified
      by the same purification procedure. A low incorporation of radioactive amino
      acids into the CS histones during early development revealed that the bulk of
      these proteins in the blastula embryo are derived from the maternal pool of the
      egg. Amino acid analysis, together with the previously described electrophoretic
      mobilities, unequivocally identified the purified proteins as CS histones.
      Peptide sequence analysis confirmed the novel nature of the CS variants as they
      are distantly related to the early, late, and sperm histone subtypes of the sea
      urchin. The CS H1 protein displays highest sequence similarity with the H1M (B4)
      histone of Xenopus laevis, indicating that the frog H1M protein may be a
      vertebrate homologue of the CS H1 histone. These data suggest an ancient
      evolutionary origin and wide distribution of the CS histone variants.

PMID- 9288899
TI  - Further characterization of a rat hepatoma-derived aldose-reductase-like protein-
      organ distribution and modulation in vitro.
AB  - A protein detected in N-methyl-N-nitrosourea-initiated rat hepatomas by two
      dimensional electrophoresis at 35 kDa/pI 7.4 was identified in a previous study
      by internal amino acid micro sequencing as an aldose-reductase-like protein
      [Zeindl-Eberhart, E., Jungblut, P. R., Otto, A. & Rabes, H. M. (1994)
      Identification of tumor-associated protein variants during rat
      hepatocarcinogenesis, J. Biol. Chem. 269, 14589-14594]. Two-dimensional
      electrophoresis of rat lens proteins revealed a spot at 37 kDa/pI 6.8 that showed
      a high degree of identity (98.5%) with rat lens aldose reductase after amino acid
      sequencing and 80% sequence identity to the rat-hepatoma-derived aldose-reductase
      like protein. This suggests that hepatoma-derived aldose-reductase-like protein
      and rat lens aldose reductase are related proteins encoded by different genes. A
      different expression profile of these proteins was found in various rat organs.
      Rat lens aldose reductase is present, in addition to in lens, in heart, brain,
      muscle, lung, duodenum, kidney, spleen and bone marrow, while the hepatoma
      derived aldose-reductase-like protein is found preferentially in hepatomas and in
      embryonic liver. Though different in organ expression, an identical response was
      found for both proteins after stimulation with fibroblast growth factor-1 and
      after exposure to increased glucose concentrations. Since rat hepatoma-derived
      aldose-reductase-like protein is expressed in embryonic, but not in adult liver,
      it is assumed that it is expressed in hepatomas as a functionally active
      embryonal type of aldose reductase during hepatocarcinogenesis.
      Immunohistochemistry revealed that the hepatoma-derived aldose-reductase-like
      protein is expressed already in the preneoplastic stage of hepatocarcinogenesis
      and might potentially serve as a marker enzyme in early hepatic neoplasia.

PMID- 9288900
TI  - Mechanism of action of sarcoplasmic reticulum calcium-uptake activators-
      discrimination between sarco(endo)plasmic reticulum Ca2+ ATPase and phospholamban
      interaction.
AB  - The Ca2+ uptake by the sarcoplasmic reticulum (SR) can be affected by direct
      modulation of the Ca2+ pump or by removing the inhibitory effect of
      dephosphorylated phospholamban. The effect of these mechanisms was assessed using
      ellagic acid and 1-(3,4-dimethoxyphenyl)-3-dodecanone. Both compounds (30
      micromol/l) enhanced SR-Ca2+ uptake in rabbit cardiomyocytes by 65.3 +/- 13% and
      44.3 +/- 6.7% for 1-(3,4-dimethoxyphenyl)-3-dodecanone and ellagic acid,
      respectively (at pCa 6.2). A similar effect was observed in cardiac SR microsomes
      (59.5 +/- 7.4% and 45.1 +/- 6.7) with 30 micromol/l 1-(3,4-dimethodoxyphenyl)-3
      dodecanone and ellagic acid, respectively. 1-(3,4-Dimethoxyphenyl)-3-dodecanone
      increased Ca2+ storage by cardiac SR microsomes mainly at high [Ca2+] with a 57%
      increase of Vmax, whereas ellagic acid increased Vmax to a smaller extent (22%)
      and stimulated Ca2+ uptake at lower [Ca2+] with a leftward-shift of the
      pCa/ATPase relationship by pCa 0.24. Ellagic acid also differed from 1-(3,4
      dimethoxylphenyl)-3-dodecanone in that it produced a Ca2+ sensitizing effect only
      in cardiac SR microsomes (by pCa 0.3) whereas 1-(3,4-dimethoxyphenyl)-3
      dodecanone stimulated the ATPase, at saturating Ca2+, in both cardiac and
      skeletal muscle SR vesicles. It is suggested that 1-(3,4-dimethoxyphenyl)-3
      dodecanone stimulates directly the Ca2+-ATPase activity, in contrast to ellagic
      acid which enhances the cardiac SR-Ca2+ uptake by interacting with phospholamban,
      as confirmed by the lack of additive effect between ellagic acid and monoclonal
      antibodies raised against phospholamban. 1-(3,4-dimethoxyphenyl)-3-dodecanone and
      ellagic acid constitute attractive pharmacological tools to investigate the
      functional consequences of enhancing SR Ca2+, uptake by affecting different
      mechanisms.

PMID- 9288901
TI  - In vitro mutagenesis of PH-20 hyaluronidase from human sperm.
AB  - The cDNA encoding PH-20 hyaluronidase from human sperm has been mutated at five
      positions by in vitro mutagenesis. We have changed three acidic amino acids and
      two arginine residues that are conserved in the sequence of mammalian PH-20
      polypeptides as well as in the hyaluronidases from bee and hornet venom. Of the
      former, the mutants [Gln113]PH-20 and [Gln249]PH-20 had no detectable enzymatic
      activity; the mutant [Asn111]PH-20 had about 3% activity. The mutant [Thr252]PH
      20 was also inactive, while [Gly176]PH-20 had only about 1% activity. This
      indicates that the PH-20 hyaluronidases, like numerous enzymes that hydrolyze
      glycosidic bonds, have acidic amino acids in their active site. Moreover, for the
      binding of the substrate, the polyanion hyaluronan, arginine residues appear to
      be essential.

PMID- 9288902
TI  - Structural studies of the O-antigenic polysaccharide of the lipopolysaccharide
      from Acinetobacter (DNA group 11) strain 94 containing 3-amino-3,6-dideoxy-D
      galactose substituted by the previously unknown amide-linked L-2-acetoxypropionic
      acid or L-2-hydroxypropionic acid.
AB  - A polysaccharide containing D-Gal, D-GalNAc, 3-(L-2-acetoxypropionamido)-3,6
      dideoxy-D-galactose (approximately 80%) and 3-(L-2-hydroxypropionamido)-3,6
      dideoxy-D-galactose (approximately 20%) was isolated by mild acid hydrolysis,
      followed by gel-permeation chromatography, from the phenol-soluble
      lipopolysaccharide (phenol/water extracted) derived from Acinetobacter strain 94.
      The polysaccharide, characterised by means of monosaccharide analyses, partial
      acid hydrolysis, and NMR studies, consisted of a branched tetrasaccharide
      repeating unit, as depicted below, in which Fucp3Nacyl represents 3-(L-2
      hydroxypropionamido)-3,6-dideoxy-D-galactose, in which approximately 80% of the
      acyl residues are O-acetylated. These Fucp3N derivatives and an O-acetylated acyl
      group are therefore constituents of bacterial LPS, but to our knowledge are not
      present in any other natural carbohydrates. [sturcture: see text]

PMID- 9288903
TI  - Subunit c from the sodium-ion-translocating F1F0-ATPase of Propionigenium
      modestum--production, purification and properties of the protein in
      dodecylsulfate solution.
AB  - Escherichia coli strain PEF42 produces a sodium-ion-dependent hybrid F1F0-ATPase
      consisting of the Propionigenium modestum subunits a, b, c and delta, of a hybrid
      alpha subunit and of the E. coli subunits beta, gamma and epsilon. The gene
      encoding subunit c of the P. modestum F1F0-ATPase was cloned into the pT7-7
      expression vector to yield plasmid pT7c. E. coli PEF42 was transformed with
      plasmid pT7c together with plasmid pGP1-2, which harbours the gene for the T7 RNA
      polymerase. The production of the P. modestum subunit c was induced by a
      temperature shift from 30 degrees C to 42 degrees C for 30 min and led to an
      increased concentration of this protein in the membrane of the host strain. The c
      subunit produced in E. coli moved as a monomer in dodecylsulfate electrophoresis.
      The protein was extracted from the cells with chloroform/methanol, purified and
      incorporated into sodium dodecylsulfate micelles. Circular dichroism of subunit c
      in sodium dodecylsulfate showed a temperature-stable spectrum (between 20-60
      degrees C) with a high proportion of alpah-helical structure. Upon incubation of
      subunit c with [14C]dicyclohexylcarbodiimide the protein became labelled in a
      sodium-ion-dependent manner, similar to the labelling observed if the purified
      F1F0-ATPase of P. modestum, was treated with the radioactive carbodiimide. The
      Na+-specific site was therefore retained in the isolated c subunit dissolved in
      dodecylsulfate.

PMID- 9288904
TI  - Cloning and biochemical characterization of an anionic peroxidase from Zea mays.
AB  - We have isolated, cloned and characterized a cDNA from Zea mays L., denoted
      ZmAP1, coding for an anionic peroxidase. The open reading frame of ZmAP1 starting
      72 residues from the 5' end of the cDNA predicts a 37,778 dalton protein of 356
      amino acid residues. The protein has high similarity to other peroxidases and
      contains two peroxidase motifs that carry two highly conserved histidines in the
      active center. We expressed recombinant ZmAP1 protein in E. coli as a fusion with
      maltose-binding protein. The fusion protein was biochemically active after
      addition of hemin to the apoprotein. The maize peroxidase ZmAP1 has a pH optimum
      at pH 4.0 and a Km of 0.2 mM for the substrate 2,2'-azino-bis-(3-ethyl
      benzothiazolin-6-sulfonic acid) at this pH. In maize seedlings the ZmAP1 gene is
      expressed predominantly in roots, the mesocotyl, the coleoptile and to a lower
      extent in the node, whereas no expression in the primary leaf was found. In situ
      hybridization shows that the expression of ZmAP1 in the young maize root is
      confined to the epidermis, hypodermis and the pericycle.

PMID- 9288906
TI  - Association of human immunodeficiency virus Nef protein with actin is
      myristoylation dependent and influences its subcellular localization.
AB  - Human immunodeficiency virus (HIV) Nef functions are thought to be mediated via
      interactions with cellular proteins. Utilizing zone velocity sedimentation in
      glycerol gradients we found that recombinant HIV-1 Nef non-covalently associates
      with actin forming a high-molecular-mass complex of 150-300 kDa. This Nef/actin
      complex was present in human B and T lymphocytes but not in insect cells and was
      dependent on the N-terminal myristoylation of Nef, whereas the SH3-binding
      proline motif of Nef was not involved. Despite being myristoylated, HIV-2 Nef did
      not associate with actin. This might reflect differences in the subcellular
      localization of Nef since cell-fractionation experiments revealed that HIV-1 Nef
      was virtually exclusively localized in the cytoskeletal (detergent-insoluble)
      fraction whereas HIV-2 Nef had significantly reduced affinity for the
      cytoskeleton. Colocalization experiments in HIV-1-infected CD4+ fibroblasts
      revealed that Nef/actin complexes may also exist in HIV-infected cells. This
      novel interaction of HIV-1 Nef with actin provides insight into the association
      of Nef with cellular structures and reveals general differences in the
      interactions of the Nef proteins from HIV-1 and HIV-2.

PMID- 9288907
TI  - The ribosomal S16 protein of Escherichia coli displaying a DNA-nicking activity
      binds to cruciform DNA.
AB  - We have recently shown that the ribosomal S16 protein of Escherichia coli is a
      magnesium-dependent DNase which introduces nicks into supercoiled DNA molecules
      [Oberto, J., Bonnefoy, E., Mouray, E., Pellegrini, O., Wikstrom, P. M. & Rouviere
      Yaniv, J. (1996) Mol. Microbiol. 19, 1319-1330]. In this work we analysed the DNA
      binding and DNA-nicking properties of S16 using two different approaches. Gel
      retardation assays showed that S16 is a structure-specific DNA-binding protein
      displaying a preferential binding for cruciform DNA structures. This specific
      binding to cruciform DNA was further investigated using a supercoiled plasmid
      carrying the origin of replication of E. coli (oriC) which is an (A+T)-rich DNA
      region with abundant palindromic sequences susceptible of forming cruciform-like
      structures in vivo. We show that the nicks introduced by S16 in oriC are not
      randomly positioned but are precisely localised near such palindromic sequences.
      In addition, the nicking activity of S16 appeared to be sequence dependent since
      the cuts introduced by S16 occurred next to an adenine, in most cases an unpaired
      adenine, usually followed by a GTT sequence. Overall these experiments indicate
      that S16 requires a cruciform-like DNA structure to bind DNA and the presence of
      a particular sequence in order to introduce specific single-stranded cuts into a
      DNA molecule.

PMID- 9288905
TI  - Molecular characterization of Fdx1, a putidaredoxin-type [2Fe-2S] ferredoxin able
      to transfer electrons to the dioxin dioxygenase of Sphingomonas sp. RW1.
AB  - Bacterium Sphingomonas sp. strain RW1 is, under aerobic conditions, able to
      degrade dibenzofuran and dibenzo-p-dioxin. The first step of the pathway is
      performed by a ring-dihydroxylating enzyme. Bunz and Cook have reported the
      purification and characterization of this dioxin dioxygenase and a ferredoxin
      able to transfer electrons to the dioxygenase [Bunz, P. V. & Cook, A. M. (1993)
      J. Bacteriol. 175, 6467-6475]. The gene encoding this [2Fe-2S] ferredoxin was
      identified by screening a genomic library constructed in pLAFR3 with a probe
      generated by a nested-PCR amplification. Primers for the amplification were
      designed based on the N-terminus sequence of the purified ferredoxin and on
      sequence comparisons with related proteins. Several cosmids were obtained and the
      ferredoxin gene, fdx1, was subcloned from one of them. The nucleotide sequence of
      a 4.6-kb DNA fragment encompassing the ferredoxin gene was determined. While in
      the case of all known multi-component dioxygenases, genes encoding the alpha and
      beta subunits are found to be contiguous with the gene of the specific electron
      carrier, the fdx1 gene in Sphingomonas sp. RW1 does not appear to be directly
      linked with the dioxin dioxygenase genes. Rather, it is clustered with genes
      apparently encoding two atypical decarboxylases/isomerases and a glutathione S
      transferase. The ferredoxin gene was hyperexpressed and the recombinant
      ferredoxin was purified. Spectroscopic characterization of Fdx1 demonstrated the
      presence of a putidaredoxin-type [2Fe-2S] cluster in this protein. Its redox
      potential was determined to be -245 (+/- 5) mV versus the normal hydrogen
      electrode at 25 degrees C, pH 8.0. Therefore, the protein is closely related to
      [2Fe-2S] ferredoxins known to be electron donors to monooxygenases involved in
      hydroxylation of aromatic compounds. Thus, this report provides clear evidence
      that a putidaredoxin-type [2Fe-2S] ferredoxin, namely Fdx1, is able to transfer
      electrons to the dioxin dioxygenase of Sphingomonas sp. RW1.

PMID- 9288908
TI  - Determination of functional domains of the human transcription factor PAX8
      responsible for its nuclear localization and transactivating potential.
AB  - The conserved structure of the transcription factors of the Pax gene family may
      reflect functional conservation. We have demonstrated that the human Pax8
      transcription factor is organized in several functional domains and contains two
      regions responsible for its nuclear localization, in addition to an activating
      region at the carboxy terminus of the protein and an inhibitory region encoded by
      the exon 9 present only in a splice variant PAX8a. Regions of PAX8 determining
      the nuclear localization of the PAX8A/lacZ fusions contain short amino acid
      sequences similar to several described nuclear localization sites (NLS). These
      NLS were identified in the paired domain and between the octapeptide and the
      residual homeodomain, respectively. The activating domain is encoded by the exons
      10 and 11 and its function is modulated by the adjacent domains encoded by the
      exons 9 and 12. The domain encoded by exon 9 significantly inhibits the function
      of the activating domain. Pax8 is expressed in thyroid cells and its product
      binds promoters of the thyroglobulin and thyroperoxidase genes through its paired
      domain. Thyroid cell growth and differentiation depend on thyrotropin which, by
      stimulating cAMP synthesis, activates the cAMP-dependent protein kinase A (PKA).
      We have investigated a link between thyrotropin stimulation and gene activation
      by Pax8. Stimulation of cAMP synthesis augments Pax8-specific transcription in
      thyroid cells, indicating that PKA is involved in Pax8 activation. Cotransfection
      of GAL4/PAX8 fusions and the catalytic subunit of PKA in A126, a PKA-deficient
      derivative of the PC12 pheochromocytoma cell line, synergistically activates the
      GAL4-specific reporter, suggesting the activating domain of PAX8 is dependent
      upon the catalytic subunit of the PKA. We propose that this dependence is due to
      a hypothetical adaptor which forms a target for PKA and interacts with the
      activating domain of PAX8. We show that PAX8 isolated from the thyroid cell line
      FTRL5 is a phosphoprotein in which phosphorylation is not dependant on cAMP
      pathway activation. Our results suggest that Pax8 is part of the cAMP signaling
      pathway and mediates thyrotropin-dependent gene activation in thyroid cells.
      Investigation of the PAX8 expression in a panel of Wilms' tumors shows a striking
      correlation between the expression of PAX8 and another transcription factor, WT1,
      indicating that these two genes may interact in vivo.

PMID- 9288909
TI  - Identification in a fish species of two Id (inhibitor of DNA
      binding/differentiation)-related helix-loop-helix factors expressed in the slow
      oxidative muscle fibers.
AB  - Helix-loop-helix (HLH) proteins related to the inhibitor of DNA
      binding/differentiation (Id) serve as general antagonists of cell
      differentiation. They lack a basic DNA-binding domain and are thought to function
      in a dominant negative manner by sequestering basic HLH (bHLH) transcription
      factors that are involved in cell determination and differentiation. Four Id
      encoding genes have been shown in mammals, they have a distinct pattern of
      expression suggesting different functions for each member in different cell
      lineage. In this study we describe the identification and cloning of two trout
      cDNAs which encode helix-loop-helix proteins showing a high degree of similarity
      with mammalian Id family members. One cDNA encodes a trout putative Id1 protein
      (TId1) that is 63% identical to the human Id1 protein over the entire length and
      78% identical within the HLH region. The other cDNA encodes a trout putative Id2
      protein (TId2) that shows 82% identity to the human Id2 protein and only one
      change that is conservative over the HLH region. In the 3' untranslated region,
      TId2 mRNA exhibits 16 nucleotides upstream from the AATAAA site, a palindromic
      sequence similar to the cytoplasmic polyadenylation element (CPE) which is also
      present in Id2 and Id3 mRNAs from mammals and in XIdx/XIdI mRNA from Xenopus. In
      the fish, TId1 and TId2 are expressed in a tissue-specific manner, with slightly
      different patterns. During myogenesis, TId1 and TId2 are highly expressed in the
      myotomal musculature of fish embryos and of early alevins but are down-regulated
      in that of late alevins. In muscle from juveniles and adults, TId1 and TId2
      transcripts are abundant in the slow oxidative fibers while they are absent in
      the fast glycolytic fibers. This expression pattern suggests that Id genes play a
      role in the regulation of muscle fiber phenotype in addition to controlling early
      myogenesis. On the whole, the identification of two HLH-Id encoding genes in a
      major taxonomic group like teleosts, suggests an early divergence of Id genes in
      vertebrate evolution. The observation that Id transcripts are present selectively
      in the slow muscle reveals that their expression is more complicated than
      previously appreciated.

PMID- 9288910
TI  - Cloning and characterization of the Oxytricha granulifera chaperonin containing
      tailless complex polypeptide 1 gamma gene.
AB  - Here we report the cloning and characterization of the Oxytricha granulifera
      CCTgamma (chaperonin containing tailless complex polypeptide 1) gene encoding a
      protein that consists of 559 amino acids. The derived amino acid sequence shares
      68% identity with Tetrahymena pyriformis CCTgamma and 58% identity with Mus
      musculus CCTgamma. The O. granulifera CCTgamma gene is located on a 2.07-kbp
      macronuclear gene-sized piece. Its transcription initiation site was determined
      by primer extension analysis. The expression of the CCTgamma gene was
      investigated by northern blot hybridization of the coding region with
      exponentially growing cells, heat shocked cells, and cells treated with 50 microM
      CdCl2. After heat shock, a decrease in the amount of the transcript compared to
      that of exponentially growing cells could be shown. In contrast, higher amounts
      of the transcript could be detected after treatment with CdCl2.

PMID- 9288911
TI  - Studies on the omega subunit of Escherichia coli RNA polymerase--its role in the
      recovery of denatured enzyme activity.
AB  - Highly purified Escherichia coli RNA polymerase contains a small subunit termed
      omega that has a molecular mass of 10,105 Da and is comprised of 91 amino acids.
      To elucidate the function of omega, whose role is as yet undefined, the subunit
      was purified to over 95% purity from an overproducing strain [BL21 (pGP1-2, pE3C
      2)]. Purified omega was then reconstituted with RNA polymerase isolated from an
      omega-less mutant. Externally added omega inhibited promoter-specific
      transcriptional activity at all promoters tested. Renaturation of fully denatured
      omega-less RNA polymerase in the presence of excess omega yielded maximum
      recovery of activity suggesting a structural rather than functional role for
      omega.

PMID- 9288912
TI  - Expression of natural and synthetic genes encoding herpes simplex virus 1
      protease in Escherichia coli and purification of the protein.
AB  - An attractive target for anti-herpes chemotherapy is the herpes simplex virus 1
      (HSV-1) protease encoded by the UL26 gene. Studies with HSV-1 strains that
      harbour mutations in the protease gene have demonstrated that the protease is
      essential for DNA packaging and virus maturation. The UL26 translation product is
      635 amino acids long and undergoes autoproteolytic processing between residues
      Ala247/Ser248 and Ala610/Ser611. The N-terminal processing product (amino acids 1
      247) contains the protease domain. To perform crystallization studies and high
      throughput screening for potent inhibitors, large amounts of the HSV-1 protease
      are required. However, expression of the natural HSV-1 protease gene in
      Escherichia coli using a T7-promoter-regulated system is low and does not allow
      for the efficient production of larger amounts of highly purified enzyme. In this
      report, we describe the use of a synthetic protease gene with optimized E. coli
      codon usage. The level of protease expression was at least 20 times higher with
      the synthetic gene as compared to the natural UL26 gene. The HSV-1 protease was
      purified to homogeneity in three steps using mixed-bed ion-exchange
      chromatography, affinity chromatography, and hydroxyapatite chromatography.

PMID- 9288913
TI  - The FLG motif in the N-terminal region of glucoprotein 41 of human
      immunodeficiency virus type 1 adopts a type-I beta turn in aqueous solution and
      serves as the initiation site for helix formation.
AB  - NMR and CD studies were carried out on a peptide representing the hydrophobic N
      terminal domain of envelope glycoprotein of human immunodeficiency virus type-1
      in solutions of varying polarity. It was found that in aquaeous solution the
      amide proton of glycine in the FLG motif resonated at a considerably high field
      and its chemical shift, within the limit of experimental precision, had a
      temperature coefficient of zero in the range studied. The upfield shift of NH of
      the glycine could be largely attributed to the ring-current effect of
      phenylalanine in the FLG motif that participated in a type-1 beta turn with a
      short Cbeta(i)-NH(i+2) distance. The slower proton-deuterion exchange for the
      glycine amide proton relative to that of other glycines was consistent with a
      folded structure for the motif in aquaeous solution. Results of the molecular
      simulation showed that this proton was shielded from the solvent by non-polar
      side chains of the amino acid residues surrounding the turn stabilized by
      hydrophobic interactions, thus explaining the zero temperature coefficient of the
      proton chemical shift. The structural stabilizing effect of the hydrophobic
      interaction was supported by the behavior of the proton in less polar Me2SO
      solution, in which the anomaly in the chemical shift and its temperature
      coefficient was less prominent. Detailed secondary-structure analysis suggested
      that the beta turn of the FLG motif may act as an initiation core for helix
      formation, probably because the turn readily transforms into helical form.

PMID- 9288915
TI  - Fourier transform infrared spectroscopic studies of proton transfer processes and
      the dissociation of Zn2+-bound water in alcohol dehydrogenases.
AB  - The following complexes were investigated by Fourier transform difference
      spectroscopy: binary complexes of alcohol dehydrogenases from yeast (YADH) and
      horse liver (LADH) with nicotinamide adenine dinucleotide (NAD+) and adenosine
      (5')-diphospho(5)-beta-D-ribose (ADP-Rib); the binary complex of Zn2+-free YADH
      with NAD+, the ternary complex of LADH with NAD+ and 2,2,2-trifluoroethanol.
      After addition of NAD+ to YADH and LADH, protonation of the N1 atom of the
      adenine ring of NAD+ is observed. It is shown that this proton arises from the
      dissociation of the Zn2+-bound water. The interaction of the Zn2+ ion with water
      is very strong, since this interaction is not just an electrostatic interaction.
      If the Zn2+ ions are in a tetrahedral environment, a large covalent contribution
      also occurs. If ADP-Rib is present instead of NAD+, no protonation of the N1 atom
      of the adenine ring of ADP-Rib is found, which demonstrates that the positively
      charged nicotinamide ring favors the conduction of the positive charge. All these
      results confirm the mechanism of Branden et al. (1975): the Zn2+-bound water is
      split and the arising (OH)- deprotonates the alcohol. In the case of the ternary
      complex of LADH with NAD+ and 2,2,2-trifluoroethanol, we demonstrate that the
      alcohol is deprotonated and the alcoholate ion is bound directly to the Zn2+ ion.
      The conduction of the proton from the active site to the N1 atom of adenine
      occurs via a hydrogen-bonded chain with large proton polarizability due to
      collective proton motion. The nature and mechanism of this pathway are discussed
      on the basis of data from previous studies.

PMID- 9288914
TI  - Efficient photoaffinity labeling of the rat V1a vasopressin receptor using a
      linear azidopeptidic antagonist.
AB  - We have synthesized and fully characterized by fast-atom-bombardment-mass, NMR
      and ultraviolet spectroscopies the vasopressin antagonist 3-azidophenylpropionyl
      D-Tyr(Me)-Phe-Gln-Asn-Arg-Pro-Arg-Tyr(3I )-NH2. Easily radioiodinatable just
      before use, it has a high affinity for the natural rat liver V1a receptor
      [dissociation constant (Kd) = 54 +/- 20 pM; Carnazzi, E., Aumelas, A., Barberis,
      C., Guillon, G. & Seyer, R. (1994) J. Med. Chem. 37, 1841-1849] and for both the
      rat vasopressin V1a receptor expressed in Spodoptera frugiperda 9 cells (Sf9
      cells, Kd = 688 +/- 35 pM) and in COS-7 cells (Kd = 320 +/- 20 pM). This probe
      labels specifically the V1a receptors in an ultraviolet-dependent manner, and
      binds covalently to about 12% of the receptors with high stability over several
      days, even in dissociation or solubilization conditions. SDS/PAGE studies and
      autoradiographic analyses of the photolabeled receptors reveal a single band
      (49.5 kDa) and two bands (63 kDa and 93.6 kDa) for receptor-probe associations
      obtained in Sf9 and COS-7 cells respectively. These molecular masses are
      consistent with non-glycosylated and highly glycosylated forms of the receptor,
      according to each expression system. In rat liver membranes, we have identified
      apparent molecular masses of about 32, 45 and more than 67 kDa. We finally
      demonstrated a proteolysis of the receptor that appeared to be Zn2+ and leupeptin
      sensitive. The high potency of this ligand is promising for the monitoring of the
      purification of the V1a receptor and for mapping its antagonist-binding site.

PMID- 9288916
TI  - Polarised expression of human intestinal N-benzoyl-L-tyrosyl-p-aminobenzoic acid
      hydrolase (human meprin) alpha and beta subunits in Madin-Darby canine kidney
      cells.
AB  - N-Benzoyl-L-tyrosyl-p-aminobenzoic acid hydrolase (PPH, human meprin), is a
      peptidase found in the microvillus membrane of human small intestinal epithelial
      cells. PPH belongs to the astacin family of zinc-metalloendopeptidases and is a
      protein complex composed of two glycosylated subunits, alpha and beta. The
      present report describes the cloning of the complete beta subunit and the
      remaining N2-terminal end of the alpha subunit for analysis of their primary
      structures in addition to the examination of their biogenesis in transfected cell
      cultures. The complete open reading frame of the PPH beta cDNA translates into
      700 amino acid residues compared with 746 residues for the PPH alpha cDNA. The
      primary structure of beta and alpha subunits are 44% identical and 61% similar.
      As predicted from their primary structure, the two subunits of PPH have identical
      modular structures; starting at the N2-terminus both contain a signal peptide, a
      propeptide, a protease domain containing the astacin signature, a meprin A5
      protein tyrosine phospatase mu (MAM) and a meprin and TRAF homology domain (MATH)
      domain, an epidermal growth factor(EGF)-like domain, a putative transmembrane
      anchor domain and a short cytosolic tail. Pulse/chase labelling and immuno-Gold
      electronmicroscopy of recombinant PPH beta and alpha subunits expressed in
      transfected Madin-Darby canine kidney (MDCK) cells show that post-translational
      processing and transport of the two subunits are very different. When expressed
      alone, the beta subunit acquired complex glycan residues, readily formed
      homodimers and was transported to the plasma membrane. Small amounts of PPH beta
      were found in the culture medium. In contrast, the cell-bound alpha subunit, when
      expressed alone, remained primarily in the high-mannose form, was aggregated and
      not expressed at the cell surface. However, the bulk of mostly endo-beta-N
      acetylglucosaminidase H-resistant alpha subunit was found in the filtered culture
      medium. The proteolytic event that leads to the formation of this soluble
      transport-competent form occurs in the endoplasmic reticulum (ER). Coexpression
      of the alpha subunit with the beta subunit allowed the localisation of the alpha
      subunit to the plasma membrane. These studies indicate that assembly of the two
      subunits of PPH is required for the localisation of the alpha subunit to the
      plasma membrane. In contrast to rodent meprin, both PPH subunits are apically
      secreted from MDCK cells.

PMID- 9288917
TI  - C-cytosolic and transmembrane domains of the N-benzoyl-L-tyrosyl-p-aminobenzoic
      acid hydrolase alpha subunit (human meprin alpha) are essential for its retention
      in the endoplasmic reticulum and C-terminal processing.
AB  - N-benzoyl-L-tyrosyl-p-aminobenzoic acid hydrolase (PPH, human meprin) is a member
      of the astacin family of Zn-metalloendopeptidases and is highly expressed in the
      microvillus membrane of human small intestinal epithelial cells. It is a type I
      transmembrane protein consisting of differentially processed glycosylated alpha
      and beta subunits. Biosynthesis experiments using transfected, metabolically
      labelled simian virus 40 (SV40) transformed african green monkey kidney cells
      (COS-1) and Madin Darby canine kidney (MDCK) cells, have previously shown that
      PPH alpha was retained in the endoplasmic reticulum (ER) and that for subsequent
      secretion removal of the alpha-tail was necessary [Grunberg, J., Dumermuth, E.,
      Eldering, J. A. & Sterchi, E. E. (1993) FEBS Lett. 335, 376-379]. We proposed an
      involvement of the alpha-tail in ER retention. To investigate the possible role
      of the transmembrane and/or the C-terminal domain of the alpha-subunit,
      tailswitch mutants were constructed in which these domains were exchanged between
      the alpha and beta subunits. Biosynthesis and post-translational processing of
      these mutants were investigated in transiently transfected COS-1 cells. The
      beta/alpha tailswitch mutant, in which the transmembrane and C-cytosolic parts of
      PPH beta were substituted by the corresponding parts of the PPH alpha subunit,
      was transported much slower compared with the wild-type PPH beta subunit. In
      addition, fusion of the alpha-tail to a C-terminally truncated secretory form of
      PPH alpha leads to its retention in the ER. This mutant, but not the secretory
      form, coimmunoprecipitated with calnexin, indicating an involvement of this
      molecular chaperone in retaining PPH alpha in the ER. The alpha/beta tailswitch
      mutant, in which the transmembrane domain and the C-cytosolic part of PPH alpha
      were substituted by the corresponding parts of PPH beta, was processed less
      efficiently in comparison with PPH alpha, resulting in a lower secretion rate.
      Taken together these data suggest a role of the alpha-tail in mediating
      association with ER-resident machinery, facilitating C-terminal processing.

PMID- 9288918
TI  - Chloroplast import of four carotenoid biosynthetic enzymes in vitro reveals
      differential fates prior to membrane binding and oligomeric assembly.
AB  - The precursor proteins of the carotenogenic enzymes geranylgeranyl diphosphate
      synthase, phytoene synthase, phytoene desaturase and lycopene cyclase were
      imported into isolated pea chloroplasts. Geranylgeranyl diphosphate synthase
      remained soluble in the stroma in a free form and phytoene synthase associated to
      thylakoid membranes upon import, both as expected. Surprisingly, phytoene
      desaturase and lycopene cyclase, which strongly depend on membrane association
      for enzymatic activity, also remained soluble in the chloroplast stroma. The
      soluble forms of these enzymes were, however, still competent for membrane
      association, e.g. with protein-free liposomal membranes. Indeed the soluble forms
      of phytoene synthase, phytoene desaturase and lycopene cyclase occurred as ATP-
      and cold-sensitive high-molecular-mass complexes. Gel-filtration experiments and
      blue native-PAGE plus autoradiography and western blot analysis indicated a
      participation of the chloroplast 60-kDa chaperonin (Cpn60) in the soluble high
      molecular-mass complexes of imported carotenogenic enzymes. Finally, it was
      inferred that a membrane-bound regulatory factor plays a decisive role in
      membrane-binding.

PMID- 9288919
TI  - Structure of the O-specific polysaccharide of Proteus vulgaris O25 containing 3-O
      [(R)-1-carboxyethyl]-D-glucose.
AB  - The O-specific polysaccharide of Proteus vulgaris O25 was studied by acid
      hydrolysis and by 1H-NMR and 13C-NMR spectroscopies, including one-dimensional
      NOE and two-dimensional COSY and heteronuclear 13C,1H correlation (HETCOR)
      spectroscopy. The polysaccharide was found to contain 3-O-[(R)-1-carboxyethyl]-D
      glucose (D-RGlc), and the following structure of the pentasaccharide repeating
      unit was established: [structure in text]

PMID- 9288920
TI  - Involvement of lysine residues in the gating of the ryanodine receptor/Ca2+
      release channel of skeletal muscle sarcoplasmic reticulum.
AB  - In this study, the modification of skeletal muscle ryanodine receptor (RyR)/Ca2+
      release channel with 7-chloro-4-nitrobenzo-2-oxa-1,3,-diazole (Nbd-Cl)
      demonstrates that lysyl residues are involved in the channel gating. Nbd-Cl was
      found to have a dual effect: stimulation and inhibition of ryanodine binding and
      single channel activities. Nbd-Cl, in a time-dependent manner, first stimulated
      and subsequently inhibited ryanodine binding to both membrane-bound and purified
      RyR. Incubation of sacroplasmic reticulum membranes with Nbd-Cl for 5-20 s
      resulted in enhanced ryanodine-binding activity by 2-4-fold due, to an increased
      binding affinity by about tenfold, with no effect on the total binding sites
      (Bmax). However, under prolonged incubation (5-20 min), Nbd-Cl strongly inhibited
      ryanodine binding by decreasing the Bmax with no effect on the binding affinity.
      Similar effects of stimulation and inhibition by Nbd-Cl were obtained with single
      channel activity of RyR reconstituted into planar lipid bilayer. Nbd-Cl initially
      (within a few seconds) activated the channel to a highly open state, then (within
      a few minutes) inactivated it to the completely closed state. Nbd-Cl-modified
      protein, as assayed by ryanodine binding or single channel activities, was stable
      against thiolysis by dithiothreitol, suggesting Nbd-Cl modification of lysyl
      residues. Evidence from absorption and fluorescence excitation and emission
      spectra also demonstrated that lysyl residues in RyR were modified by Nbd-Cl.
      Spectrophotometric data were used to estimate a ratio of up to 1 mol Nbd
      bound/mol RyR (tetramer) and up to 4 mol Nbd bound per mol RyR (tetramer) for Nbd
      Cl stimulated and inhibited RyR activities, respectively. The results clearly
      indicate the involvement of two classes of lysyl residues in RyR activity.
      Modification by Nbd-Cl of the fast-reacting group led to stimulation of ryanodine
      binding and single channel activities, while modification of the slow-reacting
      group resulted in inhibition of these activities. Thus, the involvement of lysine
      residues in the gating of the RyR channel is proposed.

PMID- 9288921
TI  - Regulation of the wound-induced myrosinase-associated protein transcript in
      Brassica napus plants.
AB  - Two slightly differing cDNA clones corresponding to the wound-inducible form of a
      previously characterized seed myrosinase-associated protein (MyAP) have been
      isolated from Brassica napus L. The transcripts corresponding to the induced MyAP
      (iMyAP) were found to be developmentally regulated in various vegetative organs.
      Both young and old leaves exhibited wound-inducible iMyAP expression.
      Furthermore, in the young plant, wounding resulted in a systemic increase in
      leaves located both acropetally and basipetally to the wounded leaf. Also, the
      iMyAP transcripts were induced by methyl jasmonate, jasmonic acid and abscisic
      acid. The different inductions could be antagonized by salicylic acid. A general
      responsiveness in methyl-jasmonate-treated leaves was demonstrated by in situ
      hybridization. No effect on the amount of iMyAP transcript was detected after
      feeding the plants with the ethylene precursor 1-aminocyclopropane-1-carboxylic
      acid. The similarity between MyAP and a lipase from Arabidopsis thaliana
      indicated a possible function in liberating acylated glucosinolates from their
      acyl group, thereby making them available for hydrolysis by the myrosinase
      enzymes. We also report on a reduction in the amount of myrosinase transcripts
      derived from the vegetatively expressed MB-gene family after treatment with
      exogenously applied salicylic acid or abscisic acid.

PMID- 9288922
TI  - Cytosolic aspartate aminotransferase encoded by the AAT2 gene is targeted to the
      peroxisomes in oleate-grown Saccharomyces cerevisiae.
AB  - Fatty acid beta-oxidation in peroxisomes requires the continued uptake of fatty
      acids or their derivatives into peroxisomes and export of beta-oxidation products
      plus oxidation of NADH to NAD. In an earlier study we provided evidence for the
      existence of an NAD(H) redox shuttle in which peroxisomal malate dehydrogenase
      plays a pivotal role. In analogy to the NAD(H)-redox-shuttle systems in
      mitochondria we have investigated whether a malate/aspartate shuttle is operative
      in peroxisomes. The results described in this paper show that peroxisomes of
      oleate-grown Saccharomyces cerevisiae contain aspartate aminotransferase (AAT)
      activity. Whereas virtually all cellular AAT activity was peroxisomal in oleate
      grown cells, we found that in glucose-grown cells most of the AAT activity
      resided in the cytosol. We demonstrate that the gene AAT2 codes for the cytosolic
      and peroxisomal AAT activities. Disruption of the AAT2 gene did not affect growth
      on oleate. Furthermore beta-oxidation of palmitate was normal. These results
      indicate that AAT2 is not essential for the peroxisomal NAD(H) redox shuttle.

PMID- 9288923
TI  - Two ribosomal DNA-binding factors interact with a cluster of motifs on the 5'
      external transcribed spacer, upstream from the primary pre-rRNA processing site
      in a higher plant.
AB  - In radish the primary processing site in pre-rRNA has been mapped to a TTTTCGCGC
      sequence (motif P) in the 5' external transcribed spacer (5' ETS) of the
      ribosomal DNA (rDNA) [Delcasso-Tremousaygue, D., Grellet, F., Panabieres, F.,
      Ananiev, E. & Delseny, M. (1988) Eur. J. Biochem. 172, 767-776]. The processing
      site is just downstream of four similar motifs named A1, A2, A3 and B. The five
      motifs constitute cluster A123BP. We have described previously that in radish
      extracts a nuclear protein, nuclear factor B (NF B) specifically binds to motif B
      [Echeverria, M., Penon, P. & Delseny, M. (1994) Mol. Gen. Genet. 243, 442-452].
      Here, by means of electrophoretic-mobility-shift assays, we describe an rDNA
      binding activity, nuclear factor D (NF D), that interacts with the A123BP
      cluster. Using various rDNA probes and competitors we show that NF D binds
      specifically to the A123 clustered motifs but not to similar B or P motifs. We
      used sequence-specific DNA-affinity chromatography to separate NF D from NF B.
      DNase I footprinting was used to map the binding site of NF D on the A123BP
      cluster and we compared it with that of NF B on the same probe. The footprint of
      NF D extends from the A1 motif to the 5' end of the NF B-binding site and
      includes motifs A2 and A3 on each strand. The footprinting of NF B is restricted
      to motif B and adjacent nucleotides. Thus the NF D-binding and NF B-binding sites
      are distinct but overlap. These two factors bind with a high specificity to the
      A123BP cluster in the radish 5' ETS. The possibility that these factors regulate
      rDNA transcription elongation at the level of the primary pre-rRNA processing
      site in crucifers is discussed.

PMID- 9288925
TI  - Heparin-induced structural modifications and oxidative cleavage of human serum
      albumin in the absence and presence of glucose--implications for transcapillary
      leakage of albumin in hyperglycaemia.
AB  - Both unfractionated and fractionated, low-molecular-mass heparins were tested on
      human serum albumin in the absence and presence of glucose at concentrations
      similar to those frequently found in diabetic hyperglycaemic patients, to
      ascertain whether heparin and glucose interfered with each other in affecting the
      conformation of albumin. Reproducible results were obtained with both heparins
      when used at equal masses, but not when used at equal molar concentrations,
      suggesting a crucial role of the amount of the saccharide units in determining
      the observed effects. Spectroscopic studies showed that the binding sites of
      glucose and heparin on albumin do not overlap and that changes in protein
      structure depend on complex and mutual interference of glucose and heparin with
      the protein, although the effects of heparin in modifying the chromophore
      environment and increasing the ordered structure of the protein also prevailed in
      the presence of glucose. Heparin binding to albumin rapidly gave rise to
      oxidative reactions, which were responsible for the increase in the carbonyl
      content of the protein together with its higher susceptibility to tryptic
      digestion. Glucose enhanced and prolonged the production of heparin-induced
      oxidants. Oxidation caused peptide bond cleavage at Lys323 in the primary
      structure of albumin, yielding two large fragments of 27.5 kDa and 35 kDa which
      aggregated to form disulphide-linked homodimers visible in SDS/PAGE as two new
      bands of 54 kDa and 74 kDa, respectively. This was accompanied with a reduction
      in Val, Glu, and Gly residues, only partially counterbalanced by an increase in
      Thr and Ser residues. While only a small percentage of albumin molecules
      underwent fragmentation in the presence of heparin with glucose, albumin turned
      out to display in an even higher proportion structural modifications consistent
      with a higher degree of ordered structure. The mechanism(s) underlying this
      heparin-driven effect and possible physiopathological implications in vivo are
      discussed.

PMID- 9288924
TI  - Guanosine 3',5'-bis(diphosphate) (ppGpp)-dependent inhibition of transcription
      from stringently controlled Escherichia coli promoters can be explained by an
      altered initiation pathway that traps RNA polymerase.
AB  - An in vitro analysis was performed to investigate the inhibitory mechanism of the
      global regulatory substances guanosine 3',5'-bis(diphosphate) (ppGpp) and
      guanosine 3'-diphosphate 5'-triphosphate (pppGpp) during initiation of
      transcription. Three promoters with well known differential ppGpp sensitivities
      in vivo were studied: the Escherichia coli rrnB P2 promoter that is only weakly
      ppGpp dependent; a P2 base change variant (P2F) that confers both stringent and
      growth rate regulation; and the completely unregulated PtacI promoter. The in
      vivo ppGpp dependency for all three promoters was verified in vitro in multiple
      round transcription reactions, reflecting a combination of the effects at
      initiation, promoter clearance, and elongation. In the main part of our study, we
      concentrated on the contribution of initiation complex formation to the overall
      inhibition of transcription. Kinetic measurements of complex association and
      dissociation revealed that at sensitive promoters (p)ppGpp triggered an
      alternative initiation pathway by RNA polymerase. This involved the stabilization
      of the initial closed complexes, and impeded open complex formation. Subsequently
      formed ternary complexes were structurally altered. Based on the above findings,
      we propose a model which suggests that ppGpp-altered RNA polymerases are
      preferentially bound and enter the alternative pathway. Thus, discrimination is
      obtained at early steps of initiation, which causes efficient inhibition at later
      steps of the transcription cycle probably involving promoter clearance and
      elongation.

PMID- 9288927
TI  - The bioactive conformation of neuropeptide Y analogues at the human Y2-receptor.
AB  - Several attempts to investigate the bioactive conformation of neuropeptide Y have
      been made so far. As cyclic peptides are much more rigid than linear ones, we
      decided to synthesise cyclic analogues of the C-terminal dodekapeptide amide
      neuropeptide Y Ac-25-36. Cyclisation was performed by side chain lactamisation of
      ornithine or lysine and glutamic or aspartic acid. The affinity of the 19
      peptides ranged from Ki 0.6 nM to greater than 10,000 nM. We found that the size,
      position, orientation, configuration. and the location of the cycle plays an
      important role for receptor recognition. Circular dichroic studies have been
      performed to characterise the secondary structure of each peptide. Receptor
      binding studies were carried out on human neuroblastoma cell lines SK-N-MC (Y1)
      and SMS-KAN (Y2), and on rabbit kidney membranes (Y2). The pharmacological and
      spectral data showed that the alpha-helix content was not the predominant factor
      for high Y2-receptor affinity. Instead, the location and the size of the
      hydrophobic lactam bridge, and the conserved C-terminal tetrapeptide (Arg-Glu-Arg
      Tyr) seemed to be the main parameters. Using molecular dynamics, the structures
      of four cyclic peptides (i,i+4) have been investigated and compared with the
      previously published NMR structure of one of the cyclic peptide analogues.
      Significant differences have been found in the overall three-dimensional fold of
      the peptides. The distances between the N- and the C-terminus allow
      discrimination between peptides with high binding affinity and those with low
      binding affinity, because of the correlation that was found with the measured
      affinity. Thus, this study suggests that a turn-like structure and the
      orientation of the C-terminus towards the N-terminus play major roles for high
      affinity binding of cyclic dodecapeptides to the Y2-receptor. None of the cyclic
      segments exhibits significant affinity to the Y1-receptor. Thus, these results
      support the hypothesis of a discontinuous binding site of neuropeptide Y at the
      Y1-receptor.

PMID- 9288928
TI  - cDNA cloning, recombinant expression, and site-directed mutagenesis of bovine
      liver carnitine octanoyltransferase--Arg505 binds the carboxylate group of
      carnitine.
AB  - The cDNA for bovine liver carnitine octanoyltransferase (COT) has been cloned by
      a combination of lambda gt11 library screening and 3' rapid amplification of cDNA
      ends (3'-RACE). The cDNA comprises 338 bases of 5' non-coding sequence, a reading
      frame of 1839 bases including the stop codon, and 820 bases of 3' non-coding DNA.
      The deduced amino acid sequence of 612 residues predicts a protein with a
      calculated mass of 70263 Da and pI 6.28. The enzyme was expressed in recombinant
      soluble form in Escherichia coli and was purified by a two-step procedure to near
      homogeneity with a yield of purified protein of 2-3 mg/l culture. Recombinant COT
      had similar kinetic properties to those of the enzyme isolated directly from beef
      liver. Arg505 in COT, conserved in all reported carnitine acyltransferase
      sequences but replaced by asparagine or isoleucine in the choline
      acetyltransferases, was converted to asparagine by site-directed mutagenesis.
      This single mutation resulted in a greater than 1650-fold increase in the Km
      value for COT towards carnitine, but had little effect on the value of k(cat) or
      the Km value for the acyl-CoA substrate. In addition, although choline was an
      extremely poor substrate for COT, the k(cat)/Km ratio towards this substrate was
      increased fourfold as a result of the mutation. These data support the notion
      that Arg505 in COT, and other carnitine acyltransferases, contributes to
      substrate binding by forming a salt bridge with the carboxylate moiety of
      carnitine.

PMID- 9288929
TI  - Isolation of the gene encoding Pyrococcus furiosus ornithine carbamoyltransferase
      and study of its expression profile in vivo and in vitro.
AB  - The gene coding for ornithine carbamoyltransferase (OTCase, argF) in the
      hyperthermophilic archaea Pyrococcus furiosus was cloned by complementation of an
      OTCase mutant of Escherichia coli. The cloned P. furiosus argF gene also
      complemented a similar mutant of Saccharomyces cerevisiae. Sequencing revealed an
      open reading frame of 314 amino acids homologous to known OTCases and preceded by
      a TATA box showing only limited similarity with the Euryarchaeota consensus
      sequence. This is in accordance with the comparatively low in vitro promoter
      activity observed in a cell-free purified transcription system. Transcription
      initiates in vivo as well as in vitro at a guanine, 22 nucleotides downstream of
      the TATA box. Upstream from argF is a putative gene for diphthine synthetase, a
      eukaryotic enzyme assumed to occur also in archaea but not in bacteria.

PMID- 9288926
TI  - Expression, purification, mass spectrometry, crystallization and multiwavelength
      anomalous diffraction of selenomethionyl PvuII DNA methyltransferase (cytosine-N4
      specific).
AB  - The type II DNA-methyltransferase (cytosine N4-specific) M.PvuII was
      overexpressed in Escherichia coli, starting from the internal translation
      initiator at Met14. Selenomethionine was efficiently incorporated into this short
      form of M.PvuII by a strain prototrophic for methionine. Both native and
      selenomethionyl M.PvuII were purified to apparent homogeneity by a two-column
      chromatography procedure. The yield of purified protein was approximately 1.8
      mg/g bacterial paste. Mass spectrometry analysis of selenomethionyl M.PvuII
      revealed three major forms that probably differ in the degree of selenomethionine
      incorporation and the extent of selenomethionine oxidation. Amino acid sequencing
      and mass spectrometry analysis of selenomethionine-containing peptides suggests
      that Met30, Met51, and Met261 were only partially replaced by selenomethionine.
      Furthermore, amino acid 261 may be preferentially oxidized in both native and
      selenomethionyl form. Selenomethionyl and native M.PvuII were crystallized
      separately as binary complexes of the methyl donor S-adenosyl-L-methionine in the
      monoclinic space group P2(1). Two complexes were present per asymmetric unit. Six
      out of nine selenium positions (per molecule), including the three that were
      found to be partially substituted, were identified crystallographically.

PMID- 9288931
TI  - Mutational analysis of domain II of flavonol 3-sulfotransferase.
AB  - The flavonol 3- and 4'-sulfotransferases (ST) from Flaveria chloraefolia catalyze
      the transfer of the sulfonate group from 3'-phosphoadenosine 5'-phosphosulfate
      (PAdoPS) to position 3 of flavonol aglycones and position 4' of flavonol 3
      sulfates. We identified previously a protein segment, designated domain II, that
      contains all the determinants responsible for the specificity of these enzymes.
      Within domain II, at least five amino acids specific to the 4'-ST that could bind
      the sulfate group of quercetin 3-sulfate were identified. In this study, these
      amino acid residues were introduced at equivalent positions in the flavonol 3-ST
      sequence by site-directed mutagenesis of the cloned cDNA. No reversal of the
      substrate specificity was observed after the individual mutations. However,
      mutation of Leu95 to Tyr had different effects on the kinetic constants depending
      on the substitution pattern of the flavonoid B ring, suggesting that the tyrosine
      side chain may be in direct contact with this part of the molecule. The function
      of conserved amino acids present in domain II was also investigated.
      Unconservative mutations at Lys134, Tyr137 and Tyr150 resulted in protein
      instability in solution, suggesting that these residues might be important for
      the structural stability of the enzyme. Replacement of Arg140 with Lys or Ser had
      no effect on protein stability, but resulted in a strong reduction in specific
      activity. The results of photoaffinity-labeling experiments with PAdoP[35S]S
      suggest that this residue is required to bind the cosubstrate. In addition, the
      reduced affinity of [Ser140]ST for 3'-phosphoadenosine 5'-phosphate (PAdoP)
      agarose indicates that Arg140 is also involved in binding the coproduct.
      Replacement of His118 with Glu or Ala resulted in a strong reduction in catalytic
      activity. However, [Lys118]ST retained a significant amount of catalytic
      activity. The results of photoaffinity-labeling experiments with PAdoP[35S]S and
      affinity chromatography on PAdoP-agarose suggest that His118 might be involved in
      catalysis in the flavonol 3-ST.

PMID- 9288930
TI  - Biochemical characterisation of ornithine carbamoyltransferase from Pyrococcus
      furiosus.
AB  - Ornithine carbamoyltransferase (OTCase) was purified to homogeneity from the
      hyperthermophilic archaeon Pyrococcus furiosus. The enzyme is a 400 +/- 20-kDa
      polymer of a 35-kDa subunit, in keeping with the corresponding gene sequence
      [Roovers, M., Hethke, C., Legrain, C., Thomm, M. & Glansdorff, N. (1997)
      Isolation of the gene encoding Pyrococcus furiosus ornithine cabamoyltransferase
      and study of its expression profile in vivo and in vitro, Eur. J. Biochem. 247,
      1038-1045]. In contrast with the dodecameric catabolic OTCase of Pseudomonas
      aeruginosa, P. furiosus OTCase exhibits no substrate cooperativity. In keeping
      with other data discussed in the text, this suggests that the enzyme serves an
      anabolic function. Half-life estimates for the purified enzyme ranged over 21-65
      min at 100 degrees C according to the experimental conditions and reached several
      hours in the presence of ornithine and phosphate. The stability was not markedly
      influenced by the protein concentration. Whereas comparative examination of
      OTCase sequences did not point to any outstanding feature possibly related to
      thermophily, modelling the enzyme on the X-ray structure of P. aeruginosa OTCase
      (constituted by four trimers assembled in a tetrahedral manner) suggests that the
      molecule is stabilized, at least in part, by a set of hydrophobic interactions at
      the interfaces between the trimers. The comparison between P. aeruginosa and P.
      furiosus OTCases suggests that two different properties, allostery and
      thermostability, have been engineered starting from a similar quaternary
      structure of high internal symmetry. Recombinant P. furiosus OTCase synthesised
      by Escherichia coli proved less stable than the native enzyme. In Saccharomyces
      cerevisiae, however, an enzyme apparently identical to the native one could be
      obtained.

PMID- 9288932
TI  - A reciprocal allosteric mechanism for efficient transfer of labile intermediates
      between active sites in CAD, the mammalian pyrimidine-biosynthetic multienzyme
      polypeptide.
AB  - Carbamoyl phosphate is the product of carbamoyl phosphate synthetase (CPS II)
      activity and the substrate of the aspartate transcarbamoylase (ATCase) activity,
      each of which is found in CAD, a large 240-kDa multienzyme polypeptide in mammals
      that catalyses the first three steps in pyrimidine biosynthesis. In our study of
      the transfer of the labile intermediate between the two active sites, we have
      used assays that differentiate the synthesis of carbamoyl phosphate from the
      overall reaction of CPS II and ATCase that produces carbamoyl aspartate. We
      provided excess exogenous carbamoyl phosphate and monitored its access to the
      respective active sites through the production of carbamoyl phosphate and
      carbamoyl aspartate from radiolabelled bicarbonate. Three features indicate
      interactions between the folded CPS II and ATCase domains causing reciprocal
      conformational changes. First, even in the presence of approximately 1 mM
      unlabelled carbamoyl phosphate, when the aspartate concentration is high ATCase
      uses endogenous carbamoyl phosphate for the synthesis of radiolabelled carbamoyl
      aspartate. In contrast, the isolated CPS II forward reaction is inhibited by
      excess unlabelled carbamoyl phosphate. Secondly, the affinity of the ATCase for
      carbamoyl phosphate and aspartate is modulated when substrates bind to CPS II.
      Thirdly, the transition-state analogue phosphonacetyl-L-aspartate is a less
      efficient inhibitor of the ATCase when the substrates for CPS II are present. All
      these effects operate when CPS II is in the more active P state, which is induced
      by high concentrations of ATP and magnesium ions and when 5'-phosphoribosyl
      diphosphate (the allosteric activator) is present with low concentrations of ATP;
      these are conditions that would be met during active biosynthesis in the cell. We
      propose a phenomenon of reciprocal allostery that encourages the efficient
      transfer of the labile intermediate within the multienzyme polypeptide CAD. In
      this model, binding of aspartate to the active site of ATCase causes a
      conformational change at the active site of the liganded form of CPS II, which
      protects it from inhibition by its product, carbamoyl phosphate; reciprocally,
      the substrates for CPS II affect the active site of ATCase by increasing the
      affinity for its substrates, endogenous carbamoyl phosphate and aspartate, and
      thus impede access of exogenous carbamoyl phosphate or the transition-state
      analogue. Reciprocal allostery justifies the close association of the enzyme
      activities within the polypeptide and ensures that carbamoyl phosphate is
      efficiently synthesised and is dedicated to the second step of pyrimidine
      biosynthesis. These conditions fulfill those required for metabolic channeling in
      the cell.

PMID- 9288933
TI  - The adenylation domain of tyrocidine synthetase 1--structural and functional role
      of the interdomain linker region and the (S/T)GT(T/S)GXPKG core sequence.
AB  - Sequence analysis of peptide synthetases revealed extensive structure similarity
      with firefly luciferase, whose crystal structure has recently become available,
      providing evidence for the localization of the active site at the interface
      between two subdomains separated by a distorted linker region [Conti, E., Franks,
      N. P. & Brick, P. (1996) Structure 4, 287-298]. The functional importance of two
      flexible loops, corresponding to the linker region of firefly luciferase and the
      highly conserved (S/T)GT(T/S)GXPKG core sequence, has been studied in view of the
      proposed conformational changes by the use of mutant analysis, limited
      proteolysis and chemical modification of tyrocidine synthetase 1. Substitution of
      the highly conserved Arg416, residing in the loop separating the subdomains of
      the adenylation domain, resulted in profound loss of activity. Limited
      proteolysis of the mutant suggested significant structural changes as manifested
      by lack of protection to degradation in the presence of substrates, revealing a
      probable disturbance of the induced-fit mechanism regulating the transformation
      from an open to a closed conformation. Mutants, obtained by replacement of the
      conserved Lys186 from the (S/T)GT(T/S)GXPKG core sequence, displayed only minor
      differences in substrate-binding affinity despite significant reduction of
      catalytic efficiency. Residue Lys186 appears to play an important role in either
      stabilization of the bound substrate through charge-charge-interactions, and/or
      fixing of the loop for maintainance of the active-site conformation.

PMID- 9288935
TI  - Expression and characterization of a lactosaminoglycan-carrying glycoprotein of
      Zajdela hepatoma cell surface--structural analysis of the carbohydrate moiety.
AB  - In poorly differentiated hepatoma cells, a glycoprotein carrying
      lactosaminoglycans is identified, and the structure of its glycan moiety is
      proposed. After membrane solubilization, protein fractionation by gel filtration,
      and electroelution, this glycoprotein (GPIII) was identified by its affinity for
      Datura stramonium lectin and its content in large glycopeptides. As shown by
      PAGE, GPIII has an apparent molecular mass of 100 kDa and is highly glycosylated
      (36%). It appears as an integral membrane glycoprotein. It is absent from normal
      hepatocytes, in that no heavy glycopeptides could be detected that bound to
      Datura lectin or to specific antiserum. The glycan moiety of GPIII has been
      analyzed according to carbohydrate composition, glycosidase treatment, affinity
      chromatography on immobilized pokeweed, Datura and Griffonia lectins, and by NMR
      and methylation analyses. The glycan is a N-linked tetraantennary
      lactosaminoglycan of 6.6 kDa, containing Gal, GlcNAc, Man, and NeuNAc in a
      16:14:3:4 molar ratio, with an average of three repeating units/branch. Its beta
      Gal residues are in the penultimate position and are linked in beta1-4 at least
      in four structural elements (three peripheral and one internal). It contains a
      very branched structure with Gal alpha1-3Gal beta1-4GlcNAc side chains linked in
      the C6 position to an inner Gal residue in a main branch. Alpha-Gal and NeuNAc
      residues [mainly NeuNAc alpha(2-3) linkage] are expressed as the nonreducing
      terminal groups. A possible structural model is proposed for this heterogeneous
      lactosaminoglycan, although no definitive structure can be established. That this
      lactosaminoglycan-carrying glycoprotein GPIII is not expressed in hepatocytes
      suggests its expression to be linked to the undifferentiated and/or malignant
      state of this hepatoma.

PMID- 9288934
TI  - All-transglycolytic synthesis and characterization of sialyl(alpha2
      3)galactosyl(beta1-4)xylosyl-p-nitrophenyl(beta1-), an oligosaccharide derivative
      related to glycosaminoglycan biosynthesis.
AB  - Beta-D-Xylopyranosides, such as p-nitrophenyl-beta-D-xylopyranoside (Xyl-Np) or 4
      methylumbelliferyl-beta-D-xylopyranoside (Xyl-MeUmb), when added to the culture
      medium of human skin fibroblasts have previously been shown to produce some Np-
      or MeUmb-oligosaccharides related to the regulation of glycosaminoglycan
      biosynthesis. Among these oligosaccharide derivatives, we synthesized the
      trisaccharide derivative NeuAc(alpha2-3)Gal(beta1-4)Xyl-Np(beta1- as a potential
      inhibitor of human skin fibroblast glycosaminoglycan biosynthesis. This synthesis
      was achieved by sequential use of transglycosylating activities of Escherichia
      coli beta-galactosidase and Trypanosoma cruzi trans-sialidase. The structure of
      the oligosaccharide obtained was determined by HPLC, ion-spray mass spectrometry,
      and NMR.

PMID- 9288936
TI  - Hypoxanthine uptake through a purine-selective nucleobase transporter in
      Trypanosoma brucei brucei procyclic cells is driven by protonmotive force.
AB  - The mechanism of purine nucleobase transport in procyclic cells of the protozoan
      parasite Trypanosoma brucei brucei was investigated. Hypoxanthine uptake at 22
      degrees C was rapid and saturable, exhibiting an apparent Km of 9.3 +/- 2.0
      microM and a Vmax of 4.5 +/- 0.8 pmol x (10(7) cells)(-1) x s(-1). All the
      natural purine nucleobases tested (Ki 1.8-7.2 microM), as well as the purine
      analogues oxypurinol and allopurinol, inhibited hypoxanthine influx in a manner
      consistent with the presence of a single high-affinity carrier. Nucleosides and
      pyrimidine nucleobases had little or no effect on hypoxanthine influx. The uptake
      process was independent of extracellular sodium, but inhibited by ionophores
      inducing cytosolic acidification (carbonyl cyanide chlorophenylhydrazone,
      nigericin, valinomycin) or membrane depolarisation (gramicidin) as well as by the
      adenosine triphosphatase inhibitors N-ethylmaleimide and N,N'
      dicyclohexylcarbodiimide. Using the fluorescent dyes bisoxonol and 2',7'-bis
      (carboxyethyl)-5,6-carboxy-fluorescein to determine membrane potential and
      intracellular pH (pHi), the rate of hypoxanthine uptake was shown to be directly
      proportional to the protonmotive force. Similarly, under alkaline extracellular
      conditions hypoxanthine uptake was reversibly inhibited alongside a reduction in
      protonmotive force. In addition, hypoxanthine accelerated the rate of pH,
      recovery to pH 7 after base-loading with NH4Cl, indicative of a proton influx
      concurrent with hypoxanthine transport. Finally, after pretreatment of cells with
      N-ethylmaleimide, hypoxanthine induced a slow membrane depolarisation,
      demonstrating that hypoxanthine transport is electrogenic. These data show that
      hypoxanthine uptake in T. b. brucei procyclic cells is dependent on the
      protonmotive force, and are consistent with a nucleobase/H+-symporter model for
      this transporter.

PMID- 9288937
TI  - The subunit f of mitochondrial yeast ATP synthase--characterization of the
      protein and disruption of the structural gene ATP17.
AB  - The subunit f of the yeast F1F0ATP synthase has been isolated from the purified
      enzyme. Amino acid composition, protein and peptide sequencing were performed.
      The data are in agreement with the sequence of the predicted product of the gene
      D9481.21 identified on the Saccharomyces cerevisiae chromosome IV. A 303-bp open
      reading frame encoding a 101-amino acid polypeptide is described. The deduced
      amino acid sequence from the ATP17 gene is 6 amino acids longer than the mature
      protein, which displays a molecular mass of 10567 Da. The protein is basic with a
      short hydrophobic segment located in the C-terminal part of the subunit. Subunit
      f remained associated with other F0 subunits upon sodium bromide treatment of the
      whole enzyme. A null mutant was constructed. The disrupted strain was unable to
      grow on glycerol medium and the mutation was recessive; rho- cells arose
      spontaneously. The null mutant mitochondria were devoid of oligomycin-sensitive
      ATPase, but still contained an active F1, while the subunits f, 6 and 8 were
      absent.

PMID- 9288938
TI  - 1H-NMR-derived secondary structure and overall fold of a natural anatoxin from
      the scorpion Androctonus australis hector.
AB  - The venom of the scorpion Androctonus australis hector contains several protein
      neurotoxins of which structure and structure/activity relationships have been
      extensively studied. It also contains polypeptides such as Aah STR1, which are
      not toxic, while having highly similar sequences to fully active toxins. We have
      determined the solution structure of Aah STR1 by use of conventional two
      dimensional NMR techniques followed by distance-geometry and energy minimization.
      We have demonstrated that, despite its lack of toxicity, Aah STR1 is structurally
      highly related to anti-mammal scorpion toxins specific for Na+ channels. The
      calculated structure is composed of a short alpha-helix (residues 26-33)
      connected by a tight turn to a three-stranded antiparallel beta-sheet (sequences
      3-6, 38-41 and 44-48). This beta-sheet is right-handed twisted as usual for such
      secondary structures. The beta-turn connecting the strands 38-41 and 44-48
      belongs to type II'. The overall fold of Aah STR1 is typical of beta-type
      scorpion toxins. This is, however, the first example of such a fold in Old World
      scorpion toxins. Either the absence of a basic residue in position 63 or the high
      mobility of loops, compared to active beta-type neurotoxins, may explain the lack
      of activity of this protein.

PMID- 9288939
TI  - Purification, characterization and partial amino acid sequencing of
      hydroxycinnamoyl-CoA:tyramine N-(hydroxycinnamoyl)transferase from tobacco cell
      suspension cultures.
AB  - We report the purification of hydroxycinnamoyl-CoA:tyramine N
      (hydroxycinnamoyl)transferase (THT) to apparent homogeneity in 12% yield from
      tobacco (Nicotiana tabacum L. cv. Xanthi) cell-suspension cultures elicited with
      a commercial preparation of pronase. The purification procedure employs only four
      chromatography steps and takes advantage of the fact that the transferase binds
      tightly both to phenyl-Sepharose and to hydroxyapatite. The native enzyme has a
      pI of 5.2 and consists of two identical or very similar subunits of approximately
      24 kDa. The purified enzyme can synthesise a wide range of amides due to its
      relatively low specificity for cinnamoyl-CoA derivatives and
      hydroxyphenethylamines, but its best substrates are tyramine and feruloyl-CoA.
      THT follows Michaelis-Menten kinetics in the presence of low concentrations of
      feruloyl-CoA but negative cooperativity occurs when this concentration increases
      above 2.5 microM, resulting in a marked decrease of the affinity for tyramine.
      Large deviations from Michaelis-Menten kinetics are also observed when 3
      methoxytyramine is used as acyl acceptor. The activity of tobacco THT is not
      affected by the addition of CaCl2 or MgCl2 but its maximal velocity is increased
      up to twofold by addition of ethanol to the assay mixture. It is inhibited in
      vitro by L-tyrosine benzyl ester, which binds reversibly to the tyramine-binding
      site. Experiments performed using L-tyrosine benzyl ester and caffeoyl-CoA as
      inhibitors confirm that feruloyl-CoA is the first substrate to add to the
      transferase in an ordered bi-bi mechanism. Part of the amino acid sequence of the
      transferase, elucidated by microsequencing of tryptic peptides, is also
      described.

PMID- 9288940
TI  - Characterization of two F-actin-binding and oligomerization sites in the cell
      contact protein vinculin.
AB  - Vinculin, a structural protein of animal cells, is critically involved in the
      assembly of microfilament/plasma membrane junctions at cell contacts. To
      understand its role in organizing the distal portions of microfilaments into
      specific, morphologically distinct structures at these sites in more detail, we
      characterized its interaction with filamentous actin and with itself by means of
      in vitro assays. Using recombinant proteins comprising different parts of the
      vinculin tail fused to the maltose-binding protein of Escherichia coli, we show
      in sedimentation assays that this part of vinculin harbors two discrete sites
      that can bind to actin independently. They reside within amino acid residues 893
      985 and 1016-1066 of the 1066-residue polypeptide chain. However, both sites are
      necessary to cross-link or bundle actin filaments, as demonstrated by low shear
      viscometry. Crosslinking and bundling are alternatives determined by the molar
      ratio of fusion protein to F-actin. Both actin-binding sequences are capable of
      oligomer formation, as shown in chemical-cross-linking and dot-overlay assays.
      These data allow us to propose a possible role for vinculin in organizing the
      distal ends of microfilaments at the plasma membrane into the point-like
      structure characteristic for cell-matrix contacts.

PMID- 9288942
TI  - Selective stimulation of a cAMP-specific phosphodiesterase (PDE4A5) isoform by
      phosphatidic acid molecular species endogenously formed in rat thymocytes.
AB  - We have previously reported that concanavalin A (ConA) stimulation of rat
      thymocytes induces an increase in the cellular phosphatidic acid mass as well as
      a change in its fatty acid composition. An increase in phosphodiesterase (PDE)
      activity, mostly due to cAMP-specific (PDE4) isoforms, has also been observed in
      thymocytes stimulated by ConA. Furthermore, phosphatidic acid was able to
      stimulate PDE4 activity in vitro. In the present study, cAMP levels have been
      shown to decrease upon ConA stimulation of thymocytes. Decreasing phosphatidic
      acid level using diacylglycerol kinase inhibitors induced a parallel decrease of
      the ConA-stimulated cAMP-specific PDE activity in these cells. Analyses of
      phosphatidic acid molecular species in cells stimulated for 5 min by ConA
      revealed a significant increase in 1-stearoyl-2-arachidonoyl-sn-glycerol-3
      phosphate and a relative decrease in the other molecular species of phosphatidic
      acid, mainly species containing palmitate. On the other hand, phosphatidic acid
      extracted from ConA-stimulated cells activated more efficiently the recombinant
      PDE4A5 isoform in vitro, as compared to phosphatidic acid extracted from
      unstimulated cells. In addition, phosphatidic acid species containing unsaturated
      fatty acids were stimulatory, while those containing two saturated fatty acids
      had only a marginal effect on the enzyme activity. Taken together, these data
      suggest that the mitogenic stimulation of thymocytes is accompanied by the
      synthesis of peculiar phosphatidic acid molecular species able to activate a PDE4
      isoform. This activation might be of physiological relevance since cAMP is a
      major negative effector of the mitogenic response.

PMID- 9288941
TI  - The heat-shock protein HslVU from Escherichia coli is a protein-activated ATPase
      as well as an ATP-dependent proteinase.
AB  - HslVU in Escherichia coli a new two-component ATP-dependent protease composed of
      two heat-shock proteins, the HslU ATPase and the HslV peptidase which is related
      to proteasome beta-type subunits. Here we show that the reconstituted HslVU
      enzyme degrades not only certain hydrophobic peptides but also various
      polypeptides, including insulin B-chain, casein, and carboxymethylated
      lactalbumin. Maximal proteolytic activity was obtained with a 1:2 molar ratio of
      HslV (a 250-kDa complex) to HslU (a 450-kDa complex). By itself, HslV could
      slowly hydrolyze these polypeptides, but its activity was stimulated 20-fold by
      HslU in the presence of ATP. The ATPase activity of HslU was stimulated up to 50%
      by the protein substrates, but not by nonhydrolyzed proteins, and this
      stimulation further increased 2-3-fold in the presence of HslV. Concentrations of
      insulin B-chain that maximally stimulated the ATPase allowed maximal rates of the
      B-chain hydrolysis. Furthermore, addition of increasing amounts of ADP or N
      ethylmaleimide reduced ATP and protein or peptide hydrolysis in parallel. Thus,
      HslVU is a protein-activated ATPase as well as an ATP-dependent proteinase, and
      these processes appear linked. Surprisingly, the protein and peptide substrates
      do not compete with each other for hydrolysis. Lactacystin strongly inhibits
      protein degradation, but has little effect on peptide hydrolysis, while the
      peptide aldehydes are potent inhibitors of hydrolysis of small peptides, but have
      little effect on proteins. Thus, the functional requirements for ATP-dependent
      hydrolysis of peptides and proteins appear different.

PMID- 9288944
TI  - Phosphorylation of human general transcription factors TATA-binding protein and
      transcription factor IIB by DNA-dependent protein kinase--synergistic stimulation
      of RNA polymerase II basal transcription in vitro.
AB  - DNA-dependent protein kinase (DNA-PK) has been known to catalyze phosphorylation
      of a number of regulatory factors involved in DNA replication and transcription
      such as simian virus 40 T antigen, p53, c-Myc, Sp1, and RNA polymerase II (Pol
      II). We examined the possibility that DNA-PK phosphorylates the general
      transcription factors TATA-binding protein (TBP) and transcription factor (TF)
      IIB, which play key roles in the formation of transcription initiation complex
      with Pol II. By using a highly purified preparation of DNA-PK from Raji cells,
      both TBP and TFIIB were shown to be phosphorylated in vitro by DNA-PK. We then
      investigated the effect of the phosphorylation of these factors on Pol II basal
      transcription. Stepwise analysis of preinitiation complex formation by
      electrophoretic mobility shift assay revealed that the phosphorylation of TBP and
      TFIIB by DNA-PK did not affect the formation of promoter (P)-TBP and P-TBP-TFIIB
      complexes but synergistically stimulated the formation of P-TBP-TFIIB-TFIIF-Pol
      II complex. Similarly, combination of the phosphorylated TBP and TFIIB
      synergistically stimulated Pol II basal transcription from adenovirus major late
      promoter. These observations suggest that DNA-PK could positively regulate the
      Pol II basal transcription by phosphorylating TBP and TFIIB.

PMID- 9288943
TI  - The regulatory functions of the gamma and epsilon subunits from chloroplast CF1
      are transferred to the core complex, alpha3beta3, from thermophilic bacterial F1.
AB  - The expression plasmids for the subunit gamma (gamma(c)) and the subunit epsilon
      (epsilon(c)) of chloroplast coupling factor (CF1) from spinach were constructed,
      and the desired proteins were expressed in Escherichia coli. Both expressed
      subunits were obtained as inclusion bodies. When recombinant gamma(c) was mixed
      with recombinant alpha and beta subunits of F1 from thermophilic Bacillus PS3
      (TF1), a chimeric subunit complex (alpha3beta3gamma(c)) was reconstituted and it
      showed significant ATP hydrolysis activity. The ATP hydrolysis activity of this
      complex was enhanced in the presence of dithiothreitol and suppressed by the
      addition of CuCl2, which induces formation of a disulfide bond between two
      cysteine residues in gamma(c). Hence, this complex has similar modulation
      characteristics as CF1. The effects of recombinant epsilon(c) and epsilon subunit
      from TF1 (epsilon(t)) on alpha3beta3gamma(c) were also investigated. Epsilon(c)
      strongly inhibited the ATP hydrolysis activity of chimeric alpha3beta3gamma(c)
      complex but epsilon(t) did not. The inhibition was abolished and the ATP
      hydrolysis activity was recovered when methanol was added to the assay medium.
      The addition of epsilon(c) or epsilon(t) to the alpha3beta3gamma(t) complex,
      which is the authentic subunit complex from TF1, resulted in weak stimulation of
      the ATP hydrolysis activity. These results suggest that (a) the specific
      regulatory function of gamma(c) can be transferred to the bacterial subunit
      complex; (b) the interaction between the gamma(c) subunit and epsilon(c) strongly
      affects the enzyme activity, which was catalyzed at the catalytic sites that
      reside on the alpha3beta3 core.

PMID- 9288945
TI  - The biochemical effect of the naturally occurring Trp64-->Arg mutation on human
      beta3-adrenoceptor activity.
AB  - A Trp-->Arg mutation at amino acid position 64 in the human beta3-adrenoceptor is
      reportedly associated with morbid obesity; carriers suffer from increased gain in
      mass, early-onset diabetes, insulin resistance, and an increased waist-to-hip
      ratio [Clement, K., Vaisse, C., Manning, B. S., Basdevant, A., Guy-Grand, B.,
      Ruiz, J., Silver, K. D., Shuldiner, A. R., Froguel, P. & Strosberg, A. D. (1995)
      N. Engl. J. Med. 333, 352-354]. Here, we report the stable expression of the
      genes encoding the wild-type or the [Arg64]beta3-adrenoceptor in two different
      cell types: hamster CHO-K1 and human HEK293. The mutated receptor displayed
      unchanged pharmacological values compared to the wild type for the binding
      inhibition (Ki) and adenylyl cyclase activation constants (K(act)) in two
      independent clones of both cell lines. However, maximal cAMP accumulation was
      significantly reduced in response to various beta3-adrenergic agonists, including
      endogenous catecholamines, (-)-epinephrine and (-)-norepinephrine, the non
      selective agonist (-)-isoproterenol, and the beta3-adrenergic selective agonist
      CGP 12177A. Treatment with Pertussis toxin did not restore the adenylyl cyclase
      activity to that of the wild type, suggesting that the reduction in cAMP
      accumulation observed in cells expressing [Arg64]beta3-adrenoceptor is not due to
      enhanced interaction of the beta3-adrenoceptor with the inhibitory Gi protein.

PMID- 9288946
TI  - Participation of a stress-activated protein kinase cascade in the activation of
      tyrosine hydroxylase in chromaffin cells.
AB  - Sodium arsenite and osmotic shock both stimulated stress-activated protein kinase
      2 (SAPK2, also termed RK, p38, CSBP and Mxi2) and its downstream target mitogen
      activated protein kinase (MAP kinase)-activated protein kinase-2 (MAPKAP-K2) in
      bovine adrenal chromaffin and rat PC12 cells. The same stimuli also increased
      tyrosine hydroxylase activity 2-3-fold and induced its phosphorylation at Ser19,
      a residue phosphorylated by MAPKAP-K2 in vitro. The arsenite-induced activation
      of tyrosine hydroxylase and its phosphorylation at Ser19 were prevented by SB
      203580 at concentrations similar to those that inhibited SAPK2 in vitro. These
      results indicate that MAPKAP-K2 mediates the stress-induced activation of
      tyrosine hydroxylase. SB 203580 had no effect on the phosphorylation or
      activation of tyrosine hydroxylase induced by nerve growth factor or forskolin,
      which trigger the phosphorylation of Ser31 and Ser40, respectively. Stimulation
      of bovine adrenal chromaffin cells with acetylcholine activated SAPK2 and MAPKAP
      K2, as well as p42/p44 MAP kinases and their downstream target MAPKAP-K1. The
      half-times for activation of MAPKAP-K1 and MAPKAP-K2 (1 min) were similar. In
      contrast, the activation of tyrosine hydroxylase by acetylcholine peaked within 1
      min and gradually declined thereafter. Neither SB 203580 (which blocked the
      activation of MAPKAP-K2 by acetylcholine) nor PD 98059 (which prevented the
      activation of p42/p44 MAP kinases by acetylcholine) affected tyrosine hydroxylase
      activation after 1 min, but these compounds inhibited activation by 40-50% after
      5 min. PD 98059 prevented the acetylcholine-induced phosphorylation of tyrosine
      hydroxylase at Ser31, the residue targetted by p42/p44 MAP kinases in vitro, but
      did not inhibit the phosphorylation of Ser40 (which is phosphorylated by MAPKAP
      K1 in vitro). Our results establish that p42/p44 MAP kinases mediate the
      acetylcholine-induced phosphorylation of tyrosine hydroxylase at Ser31. SB 203580
      did not suppress the phosphorylation of Ser19 or Ser40 by acetylcholine but, like
      PD 98059, this drug decreased the phosphorylation of Ser31. SAPK2 may therefore
      contribute to the acetylcholine-induced activation of tyrosine hydroxylase by
      facilitating (in an unknown way) its phosphorylation by MAP kinases.

PMID- 9288947
TI  - Identification of an ubiquitin-ligation system for the epidermal-growth-factor
      receptor--herbimycin A induces in vitro ubiquitination in rabbit-reticulocyte
      lysate.
AB  - Some receptor tyrosine kinases such as the receptors for epidermal-growth factor
      (EGF) and platelet-derived growth factor undergo polyubiquitination as a
      consequence of ligand binding. The EGF receptor is also ubiquitinated by
      treatment with herbimycin A, an ansamycin antibiotic widely used as a tyrosine
      kinase inhibitor. To investigate the mechanism of the receptor ubiquitination, we
      have established an assay system in which herbimycin-A-induced ubiquitination
      processes can be analyzed in vitro. We now show that herbimycin A treatment of
      the purified EGF receptor induces polyubiquitination of the receptor in rabbit
      reticulocyte lysate. Both DEAE unadsorbed material (fraction I) and high salt
      eluate (fraction II) of the reticulocyte lysate are involved cooperatively in the
      ubiquitination process, where the ubiquitin-conjugating enzyme UBC4 can
      functionally substitute for fraction I. A ubiquitin-protein ligase-like activity,
      partially purified from fraction II by DEAE anion-exchange chromatography, also
      functions in concert with UBC4. The precise mechanism of herbimycin A-induced
      ubiquitination of the EGF receptor is not fully understood, however, our present
      findings suggest that direct interaction with herbimycin A results in some
      modification of the receptor which is recognized by the ubiquitin-conjugating
      system in rabbit-reticulocyte lysate.

PMID- 9288948
TI  - ADP-binding and ATP-binding sites in native and proteinase-K-digested creatine
      kinase, probed by reaction-induced difference infrared spectroscopy.
AB  - Conformational changes induced by nucleotide binding to native creatine kinase
      (CK) from rabbit muscle and to proteinase-K-digested (nicked) CK, were
      investigated by infrared spectroscopy. Photochemical release of ATP from
      ATP[Et(PhNO2)] in the presence of creatine and native CK produced reaction
      induced difference infrared spectra (RIDS) of CK related to structural changes of
      the enzyme that paralleled the reversible phosphoryl transfer from ATP to
      creatine. Similarly the photochemical release of ADP from ADP[Et(PhNO2)] in the
      presence of phosphocreatine and native CK allowed us to follow the backward
      reaction and its corresponding RIDS. Infrared spectra of native CK indicated that
      carboxylate groups of Asp or Glu, and some carbonyl groups of the peptide
      backbone are involved in the enzymatic reaction. Native and proteinase nicked CK
      have similar Stokes' radii, tryptophan fluorescence, fluorescence fraction
      accessible to iodide, and far-ultraviolet CD spectra, indicating that native and
      modified enzymes have the same quaternary structures. However, infrared data
      showed that the binding site of the gamma-phosphate group of the nucleotide was
      affected in nicked CK compared with that of the native CK. Furthermore, the
      infrared absorptions associated with ionized carboxylate groups of Asp or Glu
      amino acid residues were different in nicked CK and in native CK.

PMID- 9288949
TI  - Obstacles of nomenclature.

PMID- 9288951
TI  - Animal researchers should 'start talking' to anti-vivisectionists.

PMID- 9288950
TI  - Exonerated researcher settles for $3m.

PMID- 9288952
TI  - Consortium aims to revive sterile-mosquito project.

PMID- 9288953
TI  - US patent office withdraws patent on Indian herb.

PMID- 9288954
TI  - Curbs on B6 highlight dietary dilemmas.

PMID- 9288955
TI  - Eugenics scandal reveals silence of Swedish scientists.

PMID- 9288956
TI  - Gourmet cannibalism in New Guinea tribe.

PMID- 9288957
TI  - Pseudo-authorship.

PMID- 9288958
TI  - Reversing the kinesin ratchet--a diverting tail.

PMID- 9288960
TI  - Epidemiology. A human germ project?

PMID- 9288959
TI  - Membrane transport. Green light for Golgi traffic.

PMID- 9288962
TI  - How hosts control worms.

PMID- 9288961
TI  - Anandamide may mediate sleep induction.

PMID- 9288963
TI  - Structure of Cre recombinase complexed with DNA in a site-specific recombination
      synapse.
AB  - During site-specific DNA recombination, which brings about genetic rearrangement
      in processes such as viral integration and excision and chromosomal segregation,
      recombinase enzymes recognize specific DNA sequences and catalyse the reciprocal
      exchange of DNA strands between these sites. The bacteriophage recombinase Cre
      catalyses site-specific recombination between two 34-base-pair loxP sites. The
      crystal structure at 2.4 A resolution of Cre bound to a loxP substrate reveals an
      intermediate in the recombination reaction, in which a Cre molecule has cleaved
      the substrate to form a covalent 3'-phosphotyrosine linkage with the DNA. Four
      recombinases and two loxP sites form a synapsed structure in which the DNA
      resembles models of four-way Holliday-Junction intermediates. The Cre-loxP
      complex challenges models of site-specific recombination that require large
      changes in quaternary structure. Subtle allosteric changes at the carboxy termini
      of the Cre subunits may instead coordinate the cleavage and strand-exchange
      reactions.

PMID- 9288964
TI  - Oxidative acylation using thioacids.
AB  - Several important prebiotic reactions, including the coupling of amino acids into
      polypeptides by the formation of amide linkages, involve acylation. Theae
      reactions present a challenge to the understanding of prebiotic synthesis.
      Condensation reactions relying on dehydrating agents are either inefficient in
      aqueous solution or require strongly acidic conditions and high temperatures.
      Activated amino acids such as thioester derivatives have therefore been suggested
      as likely substrates for prebiotic peptide synthesis. Here we propose a closely
      related route to amide bond formation involving oxidative acylation by thioacids.
      We find that phenylalanine, leucine and phenylphosphate are acylated efficiently
      in aqueous solution by thioacetic acid and an oxidizing agent. From a prebiotic
      point of view, oxidative acylation has the advantage of proceeding efficiently in
      solution and under mild conditions. We anticipate that oxidative acylation should
      prove to be a general method for activating carboxylic acids, including amino
      acids.

PMID- 9288965
TI  - RNA-catalysed carbon-carbon bond formation.
AB  - The 'RNA world' hypothesis, which assumes that the chemical processes that led to
      the appearance of life were carried out by RNA molecules, has stimulated interest
      in catalytic reactions involving oligonucleotides such as catalytic RNA
      (ribozymes). Naturally occurring ribozymes have, for example, been shown to
      efficiently catalyse the formation and cleavage of nucleic-acid phosphodiester
      bonds, and this narrow range of RNA-catalysed reactions has been subsequently
      expanded by in vitro selection methods to include ester and amide bond formation
      S(N)2 reactions and porphyrin metallations. Carbon-carbon bond formation and the
      creation of asymmetric centres are both of great importance biochemically, but
      have not yet been accomplished by RNA catalysis. A widely used reaction that
      creates two new carbon-carbon bonds and up to four stereo-centres is the Diels
      Alder cycloaddition, which occurs between a 1,3-butadiene and an alkene. Here we
      report the successful application of in vitro selection to isolate pyridine
      modified RNA molecules that catalyse a Diels-Alder cycloaddition. We find that
      the RNA molecules accelerate the reaction rate by a factor of up to 800 relative
      to the uncatalysed reaction.

PMID- 9288966
TI  - An intrinsic frequency limit to the cochlear amplifier.
AB  - Hearing in mammals depends on a feedback process within the inner ear termed the
      'cochlear amplifier'. The essential components of this amplifier are sensorimotor
      cells, the outer hair cells, which transduce motion of the basilar membrane
      induced by sound and generate forces to cancel the viscous damping of the
      cochlear partition. Outer hair cells alter the passive mechanics of the cochlea,
      enhancing both the sensitivity and the frequency selectivity of the auditory
      system. The molecular basis of the mechanism is thought to be a voltage-sensitive
      'motor' protein, as yet unidentified, embedded in the basolateral membrane of the
      outer hair cell. The cochlear amplifier operates up to at least 22 kHz, but by
      measuring both the charge and mechanical movements associated with the motor in
      isolated membrane patches under voltage clamp, we show here that the limiting
      frequency at which the motor operates lies near 25 kHz. This value therefore sets
      an upper limit to the range of hearing in mammalian cochleas using this
      mechanism. The fast charge movement, arising from charge displacement within the
      presumed motor molecule, further suggests that the protein is more likely to be
      related to a transporter than to a modified ion channel.

PMID- 9288967
TI  - Modulation of neuronal activity by target uncertainty.
AB  - Visual scenes are composed of many elements and although we can appreciate a
      scene as a whole, we can only move our eyes to one element of the scene at a
      time. As visual scenes become more complex, the number of potential targets in
      the scene increases, and the uncertainty that any particular one will be selected
      for an eye movement also increases. How motor systems accommodate this target
      uncertainty remains unknown. The activities of neurons in both the cerebral
      cortex and superior colliculus are modulated by this selection process. We
      reasoned that activity associated with target uncertainty should be evident in
      the saccadic motor system at the final stages of neural processing, in the
      superior colliculus. By systematically changing the number of stimuli from which
      a selection must be made and recording from superior colliculus neurons, we found
      that as the target uncertainty increased, the neural activity preceding target
      selection decreased. These results indicate that neurons within the final common
      pathway for movement generation are active well in advance of the selection of a
      particular movement. This early activity varies with the probability that a
      particular movement will be selected.

PMID- 9288968
TI  - PrP-expressing tissue required for transfer of scrapie infectivity from spleen to
      brain.
AB  - Much available evidence points to a pathological isoform of the prion protein PrP
      being the infectious agent that causes transmissible spongiform encephalopathies,
      but the mechanisms controlling the neurotropism of prions are still unclear. We
      have previously shown that mice that do not express PrP (Prnp[o/o] mice) are
      resistant to infection by prions, and that if a Prnp(+/+) neurograft is
      introduced into such animals and these are infected intracerebrally with scrapie,
      the graft but not the surrounding tissue shows scrapie pathology. Here we show
      that PrP-expressing neurografts in Prnp(o/o) mice do not develop scrapie
      histopathology after intraperitoneal or intravenous inoculation with scrapie
      prions. Prion titres were undetectable in spleens of inoculated Prnp(o/o) mice,
      but were restored to wild-type levels upon reconstitution of the host
      lymphohaemopoietic system with PrP-expressing cells. Surprisingly, however, i.p.
      or i.v. inoculation failed to produce scrapie pathology in the neurografts of 27
      out of 28 reconstituted animals, in contrast to intracerebral inoculation. We
      conclude that transfer of infectivity from the spleen to the central nervous
      system is crucially dependent on the expression of PrP in a tissue compartment
      that cannot be reconstituted by bone marrow transfer. Thus the requirement for
      the normal isoform of PrP in peripheral tissues represents a bottleneck for the
      spread of prions from peripheral sites to the central nervous system.

PMID- 9288969
TI  - The mouse Dazla gene encodes a cytoplasmic protein essential for gametogenesis.
AB  - RBM and DAZ/SPGY are two families of genes located on the Y chromosome that
      encode proteins containing RNA-binding motifs, and both have been described as
      candidate human spermatogenesis genes. Transmission of deletions from father to
      son has been observed in the case of DAZ, but neither gene family has been shown
      to be essential for spermatogenesis in human males. The DAZ/SPGY genes are
      particularly amenable to a knockout approach, as they are found on the Y
      chromosome in Old World primates and apes, but in other mammals, they are
      represented only by an autosomal gene, DAZLA, which is also present in Old World
      primates and apes. It has also been shown that a Dazla homologue is essential for
      spermatogenesis in Drosophila. Here we show that Dazla protein is cytoplasmic in
      male and female germ cells, unlike the nuclear RBM protein. Disruption of the
      Dazla gene leads to loss of germ cells and complete absence of gamete production,
      demonstrating that Dazla is essential for the differentiation of germ cells.

PMID- 9288970
TI  - Mechanism of inhibition of the human matrix metalloproteinase stromelysin-1 by
      TIMP-1.
AB  - Matrix metalloproteinases (MMPs) are zinc endopeptidases that are required for
      the degradation of extracellular matrix components during normal embryo
      development, morphogenesis and tissue remodelling. Their proteolytic activities
      are precisely regulated by endogenous tissue inhibitors of metalloproteinases
      (TIMPs). Disruption of this balance results in diseases such as arthritis,
      atherosclerosis, tumour growth and metastasis. Here we report the crystal
      structure of an MMP-TIMP complex formed between the catalytic domain of human
      stromelysin-1 (MMP-3) and human TIMP-1. TIMP-1, a 184-residue protein, has the
      shape of an elongated, contiguous wedge. With its long edge, consisting of five
      different chain regions, it occupies the entire length of the active-site cleft
      of MMP-3. The central disulphide-linked segments Cys 1-Thr 2-Cys 3-Val 4 and Ser
      68-Val 69 bind to either side of the catalytic zinc. Cys 1 bidentally coordinates
      this zinc, and the Thr-2 side chain extends into the large specificity pocket of
      MMP-3. This unusual architecture of the interface between MMP-3 and TIMP-1
      suggests new possibilities for designing TIMP variants and synthetic MMP
      inhibitors with potential therapeutic applications.

PMID- 9288971
TI  - ER-to-Golgi transport visualized in living cells.
AB  - Newly synthesized proteins that leave the endoplasmic reticulum (ER) are
      funnelled through the Golgi complex before being sorted for transport to their
      different final destinations. Traditional approaches have elucidated the
      biochemical requirements for such transport and have established a role for
      transport intermediates. New techniques for tagging proteins fluorescently have
      made it possible to follow the complete life history of single transport
      intermediates in living cells, including their formation, path and velocity en
      route to the Golgi complex. We have now visualized ER-to-Golgi transport using
      the viral glycoprotein ts045 VSVG tagged with green fluorescent protein (VSVG
      GFP). Upon export from the ER, VSVG-GFP became concentrated in many differently
      shaped, rapidly forming pre-Golgi structures, which translocated inwards towards
      the Golgi complex along microtubules by using the microtubule minus-end-directed
      motor complex of dynein/dynactin. No loss of fluorescent material from pre-Golgi
      structures occurred during their translocation to the Golgi complex and they
      frequently stretched into tubular shapes. Together, our results indicate that
      these pre-Golgi carrier structures moving unidirectionally along microtubule
      tracks are responsible for transporting VSVG-GFP through the cytoplasm to the
      Golgi complex. This contrasts with the traditional focus on small vesicles as the
      primary vehicles for ER-to-Golgi transport.

PMID- 9288972
TI  - Smad4 and FAST-1 in the assembly of activin-responsive factor.
AB  - Members of the TGF-beta superfamily of signalling molecules work by activating
      transmembrane receptors with phosphorylating activity (serine-threonine kinase
      receptors); these in turn phosphorylate and activate SMADs, a class of signal
      transducers. Activins are growth factors that act primarily through Smad2,
      possibly in partnership with Smad4, which forms heteromeric complexes with
      different ligand-specific SMADs after activation. In frog embryos, Smad2
      participates in an activin-responsive factor (ARF), which then binds to a
      promoter element of the Mix.2 gene. The principal DNA-binding component of ARF is
      FAST-1, a transcription factor with a novel winged-helix structure. We now report
      that Smad4 is present in ARF, and that FAST-1, Smad4 and Smad2 co
      immunoprecipitate in a ligand-regulated fashion. We have mapped the site of
      interaction between FAST-1 and Smad2/Smad4 to a novel carboxy-terminal domain of
      FAST-1, and find that overexpression of this domain specifically inhibits activin
      signalling. In a yeast two-hybrid assay, the FAST-1 carboxy terminus interacts
      with Smad2 but not Smad4. Deletion mutants of the FAST-1 carboxy terminus that
      still participate in ligand-regulated Smad2 binding no longer associated with
      Smad4 or ARF. These results indicate that Smad4 stabilizes a ligand-stimulated
      Smad2-FAST-1 complex as an active DNA-binding factor.

PMID- 9288973
TI  - Actin-dependent localization of an RNA encoding a cell-fate determinant in yeast.
AB  - The cytoplasmic localization of messenger RNA creates an asymmetric distribution
      of proteins that specify cell fate during development in multicellular
      eukaryotes. The protein Ash1 is a cell-fate determinant in budding yeast which
      localizes preferentially to the presumptive daughter nucleus, where it inhibits
      mating-type switching. Here we show that Ash1 mRNA is localized to the distal tip
      of daughter buds in post-anaphase cells. Three-dimensional imaging reveals that
      Ash1 mRNA is assembled into particles that associate with the cell cortex. To
      achieve this localization, Ash1 mRNA must have its 3' untranslated region and the
      actin cytoskeleton must be intact. Ash1 mRNA is not localized correctly in the
      absence of a myosin (Myo4) and is mislocalized to the mother-bud neck in the
      absence of a regulator of the actin cytoskeleton known as Bnil. We propose that
      Ash1 mRNA particles are transported into the daughter bud along actin filaments
      and are anchored at the distal tip. Thus, as in higher eukaryotes, Saccharomyces
      cerevisiae employs RNA localization to generate an asymmetric distribution of
      proteins and hence to determine cell fate.

PMID- 9288974
TI  - Reversal in the direction of movement of a molecular motor.
AB  - Kinesin and non-claret disjunctional (ncd) are molecular motors of the kinesin
      superfamily that move in opposite directions along microtubules. The molecular
      basis underlying the direction of movement is unclear, although it is thought to
      be an intrinsic property of the motor domain, a conserved region about 330 amino
      acids in length. The motor domain is found at the amino terminus in conventional
      kinesins, but at the carboxy terminus in ncd. Here we report on a chimaera
      composed of the motor domain of the minus-end-directed kinesin of Neurospora
      crassa. The bacterially expressed fusion protein was tested in motility assays
      using polarity-marked microtubules. Surprisingly, the chimaera moved towards the
      plus end, demonstrating that the polarity of force generation of the ncd motor
      domain has been reversed. This finding indicates that the domain organization,
      particularly the position of the motor domain, is of fundamental importance for
      the polarity of force production. It also demonstrates that the direction of
      microtubule movement is not controlled solely by the motor domain.

PMID- 9288976
TI  - Naja naja cobra bite.
AB  - Most venomous snakes in the United States are of the Crotalidae family. Another
      family of snakes, the Elapidae, are not so common, but their bites may be a
      threat to zoo keepers and persons who have exotic snakes as pets. Because
      Elapidae envenomation is not common, signs and symptoms of such envenomation may
      not be recognized. Elapidae venom, because of a curare-like property, can produce
      respiratory compromise followed by death within 10 minutes. Antivenin,
      cholinesterase inhibitors, and mechanical ventilation are treatments to consider
      in such envenomations. Unlike Crotalidae antivenin, Elapidae antivenin may not
      confer protection against species not used in its preparation. Identification of
      the involved snake, by family and specie, should be an early priority. Correct
      management of the envenomated patient is dependent on the prompt administration
      of the most specific antivenin available when indicated.

PMID- 9288975
TI  - Structure of the inhibitory receptor for human natural killer cells resembles
      haematopoietic receptors.
AB  - Abnormal cells deficient in class I major histocompatibility complex (MHC)
      expression are lysed by a class of lymphocytes called natural killer (NK) cells.
      This lysis provides a defence against pathogens and tumour cells that
      downregulate MHC expression to avoid an MHC-restricted, T-cell immune response.
      Normal cells escape lysis because their MHC molecules are recognized by NK-cell
      inhibitory receptors, which inhibit lysis. Several such inhibitory receptor
      families have been described in humans and mice. In the human killer-cell
      inhibitory receptor family, individual p58 members are specific for a subset of
      class I human leukocyte antigen (HLA)-C molecules. The human p58 natural killer
      cell inhibitory receptor clone 42 recognizes HLA-Cw4, -Cw2 and -Cw6, but not HLA
      Cw3, -Cw2, -Cw7 or -Cw8, which are recognized by p58 killer-cell inhibitor
      receptor clone 43. We have determined the X-ray structure of the p58 NK-cell
      inhibitory receptor clone 42 at 1.7-A resolution. The structure has tandem
      immunoglobulin-like domains positioned at an acute, 60-degree angle. Loops on the
      outside of the elbow between the domains form a binding site projected away from
      the NK-cell surface. The topology of the domains and their arrangement relative
      to each other reveal a relationship to the haematopoietic receptor family, with
      implications for the signalling mechanism in NK cells.

PMID- 9288977
TI  - IMG applicants to a medical residency program.

PMID- 9288978
TI  - Special issue: Communications from the 11th International Conference on Methods
      in Protein Structure Analysis.

PMID- 9288979
TI  - HIV-1 viral load in blood, semen and saliva.

PMID- 9288980
TI  - Developing intergroup nursing research in pediatric oncology.

PMID- 9288981
TI  - Lasting imprints, knowledge that changes practice.

PMID- 9288982
TI  - [Catheter ablation with radiofrequency energy in 100 patients with Wolff
      Parkinson-White syndrome].
AB  - OBJECTIVE: The aim of this paper was to evaluate our results of radiofrequency
      catheter ablation (RFCA) of accessory pathways in patients with WPW syndrome.
      STUDY PATIENTS: We studied 100 consecutive patients with WPW syndrome, 52 men and
      48 women, mean age 37 +/- 15 years who underwent RFCA. All patients were
      symptomatic, with documented episodes of supraventricular tachycardia and 9% of
      patients had underlying cardiac disease. METHODS: The RFCA was performed without
      antiarrhythmic drugs in the same session of the electrophysiologic diagnosis. The
      location of the accessory pathway site was obtained by catheter mapping, based on
      the premature and/or the presence of Kent potentials. According to the location
      of the accessory pathway, the ablation catheter was introduced either by the
      femoral vein or artery with mapping of the tricuspid or mitral ring. In the first
      cases performed energy application was manually controlled and thereafter was
      temperature guided with an upper temperature limit of 70 degrees C. We considered
      primary success criteria the disappearance of the delta wave in the surface ECG
      and the absence of ventricular preexcitation under atrial pacing and after
      adenosine injection. Clinical success was defined as the absence of clinical
      recurrence of tachycardia during the follow-up period. RESULTS: The primary
      success rate achieved was 88%; 91% in the left free wall pathways, 100% in the
      right free wall and 85% in the septal pathways (antero-septal-83%; right postero
      septal-76.5%; left postero-septal-92%). A second ablation procedure was performed
      in seven of the twelve patients with primary unsuccess obtaining a final success
      rate of 93% (left free wall-94.5%; septal pathways-91.6%). After a mean follow-up
      period of 8 +/- 7 months clinical recurrence occurred in 9% (eight patients),
      five of which are under anti-arrhythmic therapy (62.5%). Clinical success rate at
      the end of the follow-up period was 88%. CONCLUSIONS: In our experience RFCA has
      shown to be safe and with a high success rate in patients with symptomatic pre
      excitation. In this group of patients it was an effective therapy.

PMID- 9288983
TI  - [Transesophageal echocardiography in patients treated with ventilation at a
      polyvalent intensive care unit].
AB  - Transthoracic echocardiography (TTE) has a definite role in general ICUs where
      its indications are now generally accepted. Transesophageal echocardiography
      (TEE) has widened the diagnostic scope of ultrasonic and doppler technology,
      partly by resolving the physical limitations of TTE. In this article the authors
      comment on their series of TTEs and TEEs, pointing out advantages, the diagnostic
      and therapeutic implications, especially in artificially ventilated patients.
      They conclude by emphasising the need to establish TEE as a routine diagnostic
      tool in general ICUs.

PMID- 9288984
TI  - [Mitral valve insufficiency caused by tendinous cord rupture and mitral valve
      aneurysm. Significance of the echocardiographic study].
AB  - Mitral valve aneurysm is a rare complication that may occur in a myxomatous
      valve. We report the case of a 73 year old male patient with severe mitral
      regurgitation and heart failure-class IV NYHA. Echocardiography showed
      perforation of an aneurysm of the anterior leaflet of the mitral valve associated
      with rupture of tendinous cords of the posterior mitral leaflet. Diagnosis was
      made by transthoracic echocardiography and confirmed by transesophageal
      echocardiography. The patient was urgently operated with success and a mitral
      valve prosthesis was implanted.

PMID- 9288985
TI  - [Antithrombotic therapy in the elderly patient].
AB  - In 1994 there were about 100,000 deaths in Portugal (99.621), most of these (43%)
      were caused by cardiocirculatory and cerebrovascular diseases. A revision about
      antithrombotic therapy in the elderly is completely justified by the importance
      of these numbers. In respect to oral anticoagulant therapy, special attention is
      given to its use in atrial fibrillation concerning the actual therapeutic levels.
      The current recommendations point to the use of INR levels inferior to those
      usually used. An INR superior to 2.0-3.0 is only used in the case of valvular
      mechanical prosthesis. Particular importance is given to the problem of
      therapeutic induction, mentioning the principal causes of fluctuation of
      dose/response to oral anticoagulants in the elderly, with special attention to
      the possible alterations of vitamin K metabolism and the therapeutic
      interference. Finally, we specify the hemorrhagic complications of this kind of
      antithrombotic treatment, and give the recommended measures for a practical
      action for patients with a high level of INR with or without hemorrhages.
      Concerning heparin therapy, an explanation of the action of heparin and the
      principal differences between standard heparin and low molecular weight heparins
      are presented. In the elderly, we point out the secondary effects, such as
      hemorrhages, thrombocytopenia induced by heparin and osteoporosis. The usual
      measures for its minimization are related to the recommended dose and type of
      heparin administered. Finally, we approach the problem of the antiplatelet
      therapy. The current knowledge is reviewed concerning its use in primary
      prevention and the minimum dose of aspirin that seems to be effective. The use of
      aspirin in primary prevention, even if it is not well specified, can be proposed,
      in a minimum dose, in the elderly with high vascular risk (among other associated
      factors). However, some particular cases must be studied because an identical
      clinical attitude cannot be accepted for all patients. The minimum effective dose
      of aspirin is now also known to be significantly inferior to the one that has
      been used. With the possible exceptions of atrial fibrillation and valvular
      prosthesis, aspirin seems to be effective in doses of approximately 75 to 150
      mg/day. Other possibilities of antiplatelet therapy, are also analysed, with
      emphasis on platelet receptor inhibitors and metabolic inhibitors, even if their
      indications not yet been have completely established.

PMID- 9288987
TI  - [New method for the modulation of the atrioventricular conduction system in the
      treatment of atrial tachyarrhythmia. Preliminary study].

PMID- 9288986
TI  - [Ablation of the bundle of His versus modulation of the atrioventricular
      conduction system in patients with atrial tachyarrhythmia].

PMID- 9288989
TI  - [Utilization and practical significance of superficial electrocardiogram in the
      location of atrio-ventricular accessory pathways].

PMID- 9288988
TI  - [Catheter ablation of the common atrial flutter --preliminary clinical results].

PMID- 9288991
TI  - [Circadian patterns of heart rate variability in patients with dysautonomia].

PMID- 9288990
TI  - [Prevalence of late potentials in coronary patients with and without a history of
      myocardial infarction].

PMID- 9288992
TI  - [Intermittent chronotropic incompetence: an indication for permanent pacemaker?
      Report of a clinical case].

PMID- 9288993
TI  - [Acute myocardial infarction with angiographically normal epicardial coronary
      vessels].

PMID- 9288994
TI  - [Right bundle-branch block, the elevation of the ST segment in V1 to V3 and
      sudden death: the diagnostic and therapeutic approach].
AB  - In 1992, Brugada and Brugada described the "syndrome of right bundle branch
      block, persistent ST segment elevation and sudden death". This clinical and
      electrocardiographic entity, which occurs in patients with a structurally normal
      heart, has drawn the attention of many investigators. Nowadays, the occurrence of
      sudden death in otherwise asymptomatic patients with a typical ECG, and the
      transient normalization of the ECG in symptomatic patients, support the existence
      of asymptomatic and intermittent forms of this disease. The knowledge of these
      new forms and the modulation of the ECG pattern by administration of
      antiarrhythmic and autonomic drugs suggest that a functional abnormality of the
      electrical activity of the heart is responsible for this syndrome. The role of "M
      cells" in ventricular repolarization and in the occurrence of polymorphic
      ventricular arrhythmia suggests that these cells are the substrate for that
      electrical abnormality. Further studies are required to determine the appropriate
      therapeutic strategy for these patients. Until new information is available, the
      implantable cardioverter defibrillator is indicated in all symptomatic patients.

PMID- 9288995
TI  - [A comparison of unipolar versus bipolar mapping in the ablation of left-sided
      accessory atrioventricular conduction pathways].
AB  - PURPOSE: To compare the utility of unipolar versus bipolar mapping to guide
      radiofrequency catheter ablation of manifest left-sided accessory pathways.
      SETTING: University Hospital PATIENTS AND INTERVENTIONS: We studied twelve
      patients with a mean age of 42 +/- 13 years, submitted to a successful left-sided
      accessory pathway ablation. Detailed mapping was performed with the ablation
      catheter, recording simultaneous unipolar (distal electrode) and bipolar
      electrograms, in sinus rhythm. Twenty-three recordings were analyzed, including
      twelve successful, and eleven unsuccessful sites. The following measurements were
      analyzed: atrial and ventricular amplitude; interval between atrial and
      ventricular electrogram onset; interval between onset of ventricular electrogram
      and delta wave; interval between ventricular electrogram activation and delta
      wave and; unipolar morphology, classified as P-rS, P-QS or PQS. MAIN RESULTS:
      Accessory pathway ablation required a mean of 6.3 +/- 7.9 (median of 2) energy
      applications. Analysis of the electrogram revealed that ventricular activation
      was significantly earlier in successful versus unsuccessful sites. Unipolar
      morphology was also different according to the ablation result: among
      unsuccessful applications the P-rS configuration occurred in one, and the P-QS in
      ten cases, while in successful sites, seven had P-QS, and five had PQS
      morphology. CONCLUSIONS: Unipolar recordings are useful to guide radiofrequency
      catheter ablation of manifest left-sided accessory pathways and should be used in
      association with bipolar electrograms.

PMID- 9288996
TI  - [Purulent pericarditis. A 10-year retrospective study].
AB  - The authors carried out a retrospective study of 10 cases (ages below 11 years)
      with purulent pericarditis diagnosed and treated at the Coimbra Paediatric
      Hospital during a 10 year period (1 January 1985-31 December 1994). This study
      identified an average of 1 case per year, a low age group, low morbidity and nil
      mortality. Our results were due to early diagnosis and immediate aggressive
      medico-surgical managements, namely, systemic antibiotics covering the most
      common organisms during at least 3 weeks coupled with extensive
      pericardiocentesis associated with saline lavage.

PMID- 9288998
TI  - [Intensive care units for patients with cerebrovascular strokes. Are they
      worthwhile?].
AB  - In Portugal, strokes are the leading cause of mortality and one of the most
      important causes of hospital admission. An educational programme at several
      levels, involving the media, populations and health professionals, is necessary
      to reduce mortality and morbidity rates as well as the resulting high costs.
      According to international literature, stroke units have shown efficacy in the
      reduction of mortality, morbidity and costs. They are therefore worthwhile and it
      is time they were considered.

PMID- 9288997
TI  - [Systemic vasculitis as the initial presentation of a left atrial myxoma].
AB  - Left atrial myxoma remains a diagnostic challenge. The authors briefly review
      previously reported cases and their individualistic clinical and laboratory
      features. This report documents an unusual clinical presentation, initially
      directing attention to the central nervous system as well as bilateral tenderness
      and weakness of the extremities. The illness was considered to be a vasculitis
      until thirty-one months later when the diagnosis of left atrial myxoma was made.
      The tumor was successfully removed.

PMID- 9288999
TI  - [New challenges for the Sociedade Portuguesa de Cardiologia].

PMID- 9289000
TI  - [Case of myelomeningeal neurosyphilis].

PMID- 9289001
TI  - [Recent, closed trapezio-metacarpal luxation, treated by pinning.Apropos of 7
      cases with a median follow-up of 8 years].
AB  - Seven cases of acute and closed traumatic dislocation of the trapezio-metacarpal
      joint treated by percutaneous pinning adapted by Wiggins are reported with an
      average follow-up of eight years. Seven patients (five men and two women) aged 18
      to 62 were treated. The injury was due to a road traffic accident in four cases.
      The dominant hand was injured in six cases. The metacarpal base was always
      dislocated dorsally and closed reduction always remained unstable. All cases
      consisted of closed dislocation but in two cases dislocation was associated with
      upper limb fractures. On the initial radiographs no patients had degenerative
      changes. All patients were treated as an emergency or the following during the
      days injury by reduction and stabilization by one or two percutaneous kirschner
      wires followed by a scaphoid cast for three to six weeks. All patients were
      followed and reviewed for this study between two and thirteen years (mean eight
      years) after injury. Enquiries were made about return to work, pain, stability,
      range of movement, key-pinch and grasp compared with the uninjured side. The
      joint was examined radiographically with particular attention to the presence of
      subluxation and degenerative changes. 2 patients with associated complex injury
      of the upper limb developed reflex sympathetic dystrophy. 2 patients had moderate
      pain, 2 patients had limitation of joint movement, 1 patient presented a
      reduction of strength (pinch and grasp) but none had subluxation, instability, or
      degenerative changes. Closed reduction and stabilization by percutaneous pinning
      is a simple method and gives good or excellent results in the treatment of acute
      traumatic dislocation of the trapezio-metacarpal joint.

PMID- 9289003
TI  - [A significant increase in superficial sensation, a number of years after a
      peripheral neurologic lesion, using transcutaneous vibratory stimulation].
AB  - A patient with sensory changes in the territory of the ulnar nerve due to a
      partial nerve lesion 19 years previously, was treated by Transcutaneous Vibratory
      Stimulation. The effectiveness of this treatment was verified by subjective
      criteria and by the following tests: Moving and Static Two-Point discrimination
      Test, Light-touch-Deep-pressure (Semmes-Weinstein) Test, Ninhydrin sweat Test and
      Wrinkle Test. These tests document both a marked improvement in superficial
      sensitivity and partial regulation of sympathetic nervous system function.

PMID- 9289002
TI  - [Pinch deficit of the thumb-index finger due to a lesion of the anterior
      interosseous nerve. Apropos of 17 cases].
AB  - We report 17 cases of abnormal pinch due to anterior interosseous nerve (AIN)
      palsy. The AIN lesion was complete with palsy of flexor pollicis longus (FPL) and
      Flexor digitorum profondus of the second digit (FDP2) in nine cases. A partial
      lesion with FPL palsy was observed in four cases, and FDP2 in four other cases.
      Three of this eight cases were initially considered to be tendon ruptures.
      Electrodiagnosis assessed AIN lesion and respect of the main median trunk in all
      cases. Pronator quadratus examination provided the diagnosis in 14/17 cases and
      FPL or FPD2 examination established the diagnosis in the other 3 cases.
      Associated nerve lesions were found in four cases. Pinch grip was spontaneously
      recovered in 9/10 cases. The AIN lesion was due to compression in 3 cases and to
      mononeuritis such as Parsonage Turner neuralgic amyotrophy in 14 cases. As 2/3
      cases of compression resolved spontaneously, surgery indications are rare and
      should not be considered before 12 to 16 months when the lesion is not traumatic.

PMID- 9289005
TI  - [Metastasis of an adenocarcinoma of the colon to the 1st metacarpal bone].
AB  - The authors report a clinical case of metastasis to the first metacarpal arising
      from carcinoma of the colon, treated surgically four years previously. Clinical
      examination revealed painful swelling over the right thenar eminence. The
      diagnosis was established by radiology and needle biopsy. No treatment was
      administered and the patient died one month later. Metastases of the hand are
      uncommon and, according to the review of the international literature concerning
      bone metastases in the hand conducted by Kerin (1987), are usually secondary to
      lung, renal and breast cancers. Only a few cases have been described in the
      literature of bone metastases of the hand from carcinoma of the colon. The
      authors feel that some of these cases probably remain undiagnosed, as they are of
      secondary importance in view to the severity of the disease.

PMID- 9289004
TI  - [Repeated rupture of the extensor tendons of the hand due to fluoroquinolones.
      Apropos of a case].
AB  - Fluoroquinolone toxicity on cartilages and tendons has been well known since
      1983. Tendon inflammation or rupture has been described. Achilles tendon rupture
      is the most frequent complication but many other sites of tendon injuries have
      been reported. This article presents a case of rupture of extensor tendons of the
      hand in an elderly woman treated by fluoroquinolones. As far as we know, this
      site of tendon lesion has never been previously described. Histological
      examination of tendon injuries was possible after surgical treatment.
      Histological structures were similar to the classical description but had
      specific features. Like other authors, we think that the mechanism of the disease
      involves vascular disorders as well as direct toxicity. The histological lesions
      seem to be different in chronic and acute forms.

PMID- 9289006
TI  - [An experimental study of a cyanoacrylate biological adhesive in view of its use
      in the fixation of various fractures of the fingers].
AB  - Following certain interesting results reported in publications by researchers
      from the nineteen-sixties up to the present time, we decided to experiment a
      particular adhesive with high adhesive properties: this is composed of monomers
      of alpha-cyanoacrylate ethyl-2-alpha-cyanoacrylate. For this end, experiments
      were performed on 15 adult chickens, aged around 4 months, weighing 2 kg, divided
      into 5 groups of 3 chickens each. In each chicken, a rectangular bone fragment
      from the proximal-middle third of the tibia was prepared, completely separated,
      and then subsequently re-positioned and fixed with the adhesive plus collagen. At
      pre-established intervals (7, 14, 21, 30 and 60 days), each group of chickens was
      examined by x-rays and then killed, so that the particular anatomical part under
      examination could be studied both microscopically and macroscopically. The aim of
      these experiments was to evaluate the ability of cyanoacrylate adhesive to ensure
      setting of small bone-fragments that would otherwise be unstable. The results
      obtained showed the following: good stability of the bone fragment; good bone
      consolidation; absence of foreign body reactions. The positive nature of these
      results leads us to propose the use of this adhesive in hand surgery.
      Nevertheless, duty requires that further experiments be performed in order to
      acquire even greater guarantees for the positive results obtained.

PMID- 9289007
TI  - [Compression of the ulnar nerve at the wrist due to an arthro-synovial cyst.
      Apropos of 2 cases].
AB  - The authors report two cases of ulnar nerve compression at the wrist due to
      arthrosynovial cysts arising from the hamatotriquetral joint. The absence of
      strict parallelism between the type of neurological deficit observed, the site of
      the cyst and the site of compression requires ulnar nerve release as far as its
      division in the pisi-unciform hiatus, where the section of the hypothenar fibrous
      arcade and pisi-unciform ligament is essential. Complete recovery of these 2
      patients confirmed the favourable prognosis of this form of compression provided
      surgical treatment is performed early and rigorously.

PMID- 9289008
TI  - [Retrosternal luxation of the clavicle. Apropos of 4 cases surgically treated
      using a temporary screwed anterior plate and review of the literature].
AB  - The authors report 4 new cases of retrosternal dislocation of the clavicle
      operated by capsular and ligament restoration, and temporary stabilization by
      anterior plating. The 4 patients were men with a mean age of 17.5 years. The
      lesion was caused by a sports injury (football, rugby) in 3 out of 4 cases and
      was related to an indirect mechanism. Clinical examination allowed the diagnosis,
      was related to based on painful palpation of a dip over the joint, supported by
      radiology and computed tomography. CT did not reveal the epiphyseal separation
      present in two cases. Complications were frequent: 1 case of tracheal
      compression, 2 cases of temporary paresthesia of the upper limb, 2 cases of
      venous compression with one case of subclavian and medial jugularis venous
      thrombosis, 1 hemopneumothorax. Surgical reduction was performed in all 4 cases
      after 2 failures of attempted orthopedic treatment under general anesthesia. All
      patients recovered a full range of movement, a painless shoulder and no
      recurrence has been observed. All complications resolved after reduction. Venous
      thrombosis responded favourably after 6 months of anticoagulant therapy. One
      plate breakage was observed with no clinical implications. On the basis of an
      extensive review of the literature, the authors discuss the epidemiology,
      pathology and the importance of associated injuries, which are frequent and
      sometimes serious, justifying urgent reduction. Computed tomography is the most
      useful radiologic modality, both for diagnosis and for investigation of
      complications. Orthopedic treatment must be attempted first (especially in
      children) according to a well systematized technique. One third of attempts fail,
      and cases of delayed diagnosis and serious vascular complications, then require
      surgical treatment. The costoclavicular ligament is repaired either by Burrows's
      ligamentoplasty or by bone suture; the clavicle is stabilized by bone suture or
      by anterior plating. The authors do not advocate either joint fixation by
      Kirschner wire, or resection of the medial end of the clavicle.

PMID- 9289010
TI  - The 6th International Conference on Malignant Lymphoma. Proceedings, part 2.
      Lugano, Switzerland, June 5-8, 1996.

PMID- 9289009
TI  - Hearstart's arresting success.

PMID- 9289011
TI  - Binding of two novel bisdaunorubicins to DNA studied by NMR spectroscopy.
AB  - In the search for new generations of anthracycline drugs, lower cytotoxic side
      effects and higher activity against resistant cancer cells are two major goals. A
      new class of bis-intercalating anthracycline drugs has been designed,
      synthesized, and shown to have promising activity against multidrug-resistant
      cells. Two daunorubicins symmetrically linked together via a p-xylenyl group,
      either at their N3' (compound WP631) or N4' sites (compound WP652), exhibit
      extraordinary DNA binding affinities. We have used high-resolution NRM studies to
      understand the DNA binding mode of these two new bis-daunorubicin anticancer
      compounds. The structures of the WP631-d(ACGTACGT)2 and the WP652-d(TGTACA)2
      complexes have been determined by NOE-restrained refinement. WP631 binds strongly
      to the 5'-CG(A/T)(A/T)CG hexanucleotide sequence, with the aglycons intercalated
      between the two CpG sites at both ends of the hexanucleotide sequence. The
      overall conformation of the WP631-d(CGTACG)2 part is remarkably similar to the
      crystal structure of the 2:1 complex of daunorubicin and d(CGTACG)2, as predicted
      previously [Gao, Y.-G., & Wang, A.H.H. (1996), J. Biomol. Struct. Dyn. 13, 103
      117]. In contrast, the related bis-intercalator WP652 prefers the 5'-PyGTPu
      tetranucleotide sequence, with the aglycons intercalated between the PypG and
      TpPu sites. The binding of WP652 to DNA results in a severely distroted B-DNA
      duplex with the p-xylenyl tether moiety significantly protruded away from the
      bottom of the minor groove. While WP652 in some ways behaves similarly to other
      anticancer bis-intercalating antibiotics (e.g., triostine A and echinomycin), the
      detailed interactions between those two classes of bis-intercalators are quite
      different.

PMID- 9289012
TI  - Glutamate-194 to cysteine mutation inhibits fast light-induced proton release in
      bacteriorhodopsin.
AB  - Substitution of glutamic acid-194, a residue on the extracellular surface of
      bacteriorhodopsin, with a cysteine inhibits the fast light-induced proton release
      that normally is coupled with the deprotonation of the Schiff base during the L
      to M transition. Proton release in this mutant occurs at the very end of the
      photocycle and coincides with deprotonation of the primary proton acceptor, Asp
      85, during the O to bR transition. the E194C mutation also results in a slowing
      down of the photocycle by about 1 order of magnitude as compared to the wild type
      and produces a strong effect on the pH dependence of dark adaptation that is
      interpreted as a drastic reduction or elimination of the coupling between the
      primary proton acceptor Asp-85 and the proton release group. These data indicate
      that Glu-194 is a critical component of the proton release complex in
      bacteriorhodopsin.

PMID- 9289013
TI  - Antenna excited state decay kinetics establish primary electron transfer in
      reaction centers as heterogeneous.
AB  - The decay of the excited primary electron donor P* in bacterial photosynthetic
      reaction centers (both membrane-bound and detergent-isolated) has been observed
      to be nonexponential on a time scale of some tens of picoseconds. Although the
      multipicosecond nonexponentiality of P* has been ascribed to heterogeneity in teh
      rate of primary electron transfer (PET), the decay kinetics can be interpreted
      equally well using homogeneous models. To address this ambiguity, we studied the
      decay of excited bacteriochlorophyll (Bchl) in the membrane-bound core
      antenna/reaction center complexes of wild-type and mutant reaction center strains
      of Rhodobacter capsulatus. Reaction centers isolated from these same strains
      display a range of multiexponentiality in primary charge separation. The mutant
      strains carry substitutions of amino acids residing near the monomeric Bchl on
      the active and/or inactive sides of the reaction center. Transient absorption
      measurements monitoring the Qy bleach of antenna Bchls require at least two
      exponential components to fit all decays. The wild type was fitted with equal
      amplitude components whose lifetimes are 24 and 65 ps. The shortest-lived
      component is relatively insensitive to mutation, in contrast to the longer-lived
      component(s) whose amplitude and magnitude were dramatically perturbed by amino
      acid substitutions. Unlike the situation with isolated reaction centers, here the
      only kinetic models consistent with the data are those in which the primary
      electron-transfer rate constant is heterogeneous, suggesting at least two
      structural populations of RCs. PET in the population with the shortest-lived
      antenna decay causes the kinetics to be transfer-to-trap-limited, whereas the
      kinetics in the other population(s)--having longer-lived antenna decays--are
      limited by the rate of PET. Observation of both types of kinetic limitation
      within a single light-harvesting system is unexpected and complicates any
      discussion of the rate-limiting step of light energy utilization in
      photosynthesis.

PMID- 9289014
TI  - Microsecond protein folding kinetics from native-state hydrogen exchange.
AB  - Native-state amide proton (NH) exchange in turkey ovomucoid third domain (OMTKY3)
      has been used to determine rates of unfolding and folding at the 13 most slowly
      exchanging residues. Ten of the 13 NHs have previously been demonstrated to
      exchange via complete unfolding of OMTKY3 while the remaining three exchange more
      slowly than expected on the basis of thermal stability alone [Swint-Kruse, L.,
      Robertson, A. D. (1996) Biochemistry 35, 171-180]. Rates of unfolding and folding
      have been determined by monitoring MH exchange over a range of pH where (1) the
      free energy of unfolding for third domain, about 7 kcal/mol, is insensitive to pH
      and (2) the mechanism of exchange changes from one governed by a rapid
      equilibrium preceding the chemistry of exchange (i.e., EX2 exchange) to one where
      exchange is limited by the rate of unfolding (i.e., EX1 exchange). The pH
      dependence of exchange has then been fit to a two-state model to obtain the
      unfolding and folding rates. Unfolding rates at these 13 NHs in native third
      domain range from 0.003 to >/= 0.03 s-1. No correlation is observed between
      opening rates and the free energies measured at the same NHs: for example, the
      slowest and most rapid opening rates occur at Leu 23 and Asn 33, respectively,
      and these two NHs show very similar free energies of 6.7 and 6.9 kcal/mol,
      respectively. In contrast, folding rates show a positive correlation (R2 = 0.90)
      with free energies, the most rapid folding occurring at the sites with the
      largest free energies. folding rates are most rapid, 10(3)-10(4) s-1, in the
      middle of the helix, intermediate rates of around 10(3) s-1 are found in the
      remainder of the helix and through much of the beta-sheet, and the slowest
      folding, 10(2)-10(3) s-1, occurs at the juncture between the helix and sheet.
      Overall, MH exchange from native proteins provides remarkable structural and
      temporal precision for measuring very rapid conformational fluctuations.

PMID- 9289015
TI  - Gelsolin activates DNase I in vitro and cystic fibrosis sputum.
AB  - Because actin can form a complex in vitro containing both gelsolin and DNase I,
      gelsolin and DNase I have been assumed to bind independently to actin. Although
      this assumption is consistent with the known crystalline structures of gelsolin
      with one actin and of actin with DNase I, which suggest that the binding sites on
      actin for both gelsolin and DNase I are distinct and separate, we propose that a
      second actin binding site on gelsolin competes with DNase I for actin. Since
      actin is an inhibitor of DNase I, competition at the second binding site results
      in activation of DNase I by gelsolin. Covalent cross-linking experiments confirm
      that DNase I prevents dimerization of actin by gelsolin, consistent with
      displacement of one actin from gelsolin by DNase I. Activation of DNase I by
      gelsolin is a novel function for a cytoskeletal protein and could have broad
      implications for biology, such as a role in initiating apoptosis. These results
      also may explain why both gelsolin and DNase I decrease sputum viscosity in
      cystic fibrosis (CF). While the activity of DNase I had originally been
      attributed to fragmentation of DNA, subsequent data suggested that both gelsolin
      and DNase I may affect viscosity by depolymerizing filamentous actin. The current
      results alternatively suggest aht dissociation of the actin-DNase I complex by
      gelsolin in CF sputum results in activation of the nuclease activity of
      constitutive DNase I. The nuclease activity of DNase I alone is therefore
      sufficient to explain the effects of both gelsolin and DNase I on CF sputum.

PMID- 9289016
TI  - Distinct but overlapping epitopes for the interaction of a CC-chemokine with
      CCR1, CCR3 and CCR5.
AB  - Chemokines play an important role in inflammation. The mechanism via which they
      bind to more than one receptor and activate them is not well understood. The
      chemokines are thought to interact with their receptors via two distinct sites,
      one necessary for binding and the other for activation of signal transduction. In
      this study we have used alanine scanning mutagenesis to identify residues on
      RANTES that specifically interact with its receptors CCR1, CCR3, and CCR5 for
      binding and activation. Residues within a potential receptor binding site known
      as the N-loop (residues 12-20) and near the N-terminus of RANTES were
      individually mutated to alanine. The results of this study show that, within the
      N-loop, the side chain of R17 is necessary for RANTES binding to CCR1, F12 for
      binding to CCR3, and F12 and I15 for binding to CCR5, thus forming distinct but
      overlapping binding epitopes. In addition, our finding that P2 is necessary for
      binding to CCR5 is the first to show that a residue near the N-terminus of a CC
      chemokine is involved in binding to a receptor. We have also found that P2, D6,
      and T7 near the N-terminus are involved in activating signal transduction via
      CCR1, P2 and Y3 via CCR3, and Y3 and D6 via CCR5. These results indicate that
      RANTES interacts with each of its receptors in a distinct and specific manner and
      provide further evidence to support the two-site model of interaction between
      chemokines and their receptors.

PMID- 9289017
TI  - Three-dimensional structure of the cytoplasmic face of the G protein receptor
      rhodopsin.
AB  - Rhodopsin is a G protein receptor from a many-membered family of membrane
      receptors. No high-resolution structure exists for any member of this family due
      to the insolubility of membrane proteins and the difficulty in crystallizing
      membrane proteins. Two new approaches to the structure of rhodopsin are described
      that circumvent these limitations: (1) individual solution structures of the four
      cytoplasmic domains of rhodopsin are fitted with the transmembrane domain; (2)
      the solution structure of a complex of the four cytoplasmic domains is determined
      from nuclear magnetic resonance data. The two structures are similar. To test the
      validity of these structures, specific site-to-site distances measured on intact
      membrane-bound rhodopsin are compared to the same distances on the structures
      reported here. Excellent agreement is obtained. Furthermore, the agreement is
      obtained with distances measured on the activated form of teh receptor and not
      with distances on the dark-adapted form of rhodopsin. This approach may prove to
      have general applicability for the determination of the structure for membrane
      proteins.

PMID- 9289018
TI  - 3rd International Society for the Advancement of Respiratory Psychophysiology
      (ISARP) Congress. Nijmegen, The Netherlands, August 26-27, 1996. Abstracts.

PMID- 9289019
TI  - [Swan song on the Swan-Ganz catheter?].

PMID- 9289020
TI  - [Mild and moderate hypothermia as a new therapy concept in treatment of cerebral
      ischemia and craniocerebral trauma. Pathophysiologic principles].
AB  - Hypothermia protects the brain and other vital organs during periods of
      ischaemia. We differentiate between mild (36-34 degrees C), moderate (33-29
      degrees C), deep (28-17 degrees C) and profund (16-4 degrees C) hypothermia.
      During hypothermia, cerebral metabolic rate and cerebral blood flow decrease
      dependent on temperature. The relation between temperature and cerebral
      metabolism is expressed by the temperature coeffizient Q10, which is the ratio
      between two metabolic rates separated by 10 degrees C. The following factors
      contribute to decreases in cerebral blood flow seen during hypothermia: cerebral
      metabolic depression, decreases in cardiac output, and decreases in arterial
      blood pressure with pH-stat management, increases in hematocrit and in blood
      viscosity. Mild or moderate hypothermia reduces histopathological damage and
      neurological deficits if started before and during cerebral ischaemia.
      Hypothermia may also improve neurologic outcome if initiated following focal
      cerebral ischaemia, but is less effective after global ischaemic insults. Mild
      hypothermia appears to be safer and more effective compared to moderate
      hypothermia. In most instances, deep hypothermia renders neurologic outcome
      worse, which is most likely related to the generation of toxic metabolites and
      inadequate myocardial function during rewarming. The neuroprotective effects of
      hypothermia are related to several mechanisms along the ischaemic cascade:
      prevention of postischaemic hypoperfusion, reduction of functional and basal
      metabolism, decreased accumulation of lactic acid and oedema formation,
      inhibition of excitatory neurotransmitter release, prevention of Ca(++)- and
      Na(+)-influx, inhibition of lipid peroxidase activity, and free radical
      formation, stimulation of regenerative immediate early genes. The side effects of
      hypothermia include myocardial ischaemia, cardiac arrhythmias, decreased left
      ventricular contractility, coagulation abnormalities, and suppression of
      metabolic and immunological processes.

PMID- 9289022
TI  - [Comparison between continuous and intermittent thermodilution measurement of
      cardiac output during coronary artery bypass operation].
AB  - PURPOSE OF THE STUDY: Continuous recording of cardiovascular parameters ranks
      high in cardioanaesthesia. Various methods to measure the cardiac output have
      been developed within a period of a few years. We compared the bolus
      thermodilution method (COI), which has been internationally adopted as "gold
      standard" method, with the continuous thermodilution method (CCO) for measuring
      the cardiac output by means of the CCO Vigilance Monitor. Our aim was to find out
      whether cardiac output can be determined with valid results during coronary
      artery bypass surgery when using CCO. METHOD: A flow-directed catheter was used
      (8 Fr. Intelli-Cath CCO PA) in 98 patients during coronary artery bypass surgery
      after initiation of anaesthesia, introducing the catheter via the right
      V.jugularis interna, for continuous measurement of the cardiac output via the CCO
      Vigilance Monitor. The same equipment was also used to measure the cardiac output
      via the bolus thermodilution method (COI mode) at the following stages: after
      abandoning the CCO mode 10 minutes subsequent to beginning the operation before
      sternotomy; 10 minutes after sternotomy before connecting to the heart-lung
      machine; 15 minutes after disconnecting the heart-lung machine before closing the
      thorax; and 10 minutes after closing the thorax. As a corresponding comparative
      value of the CCO method, we used the average cardiac output value calculated for
      each of the four times of measurement for the last three minutes before applying
      the boli. RESULTS: In regression analysis we chose the linear model CCO = b x COI
      with gradient b = 1 and zero point ordinate a = 0. The identity measures,
      Spearman's rank correlation coefficients, and linear regression coefficients
      calculated for the four times of measurement, showed good agreement. Scatter of
      the paired differences between both methods (CCO-CCI) did not have any
      deterministic structure at all times of measurement. The average bias at the 4
      times of measurement was 0.10 l/min, -0.12 l/min, -0.1 l/min, and -0.03 l/min,
      respectively, with a precision = 2 x s of 1.17 l/min, 1.36 l/min, 1.69 l/min and
      1.50 l/min, respectively. The average relative error (100 x [CCO-COI]/COI) with
      standard deviation was calculated for the 4 times of measurement as 3.2% (s =
      15.4%), -1.6% (s = 15.3%), -0.9% (s = 13.9%) and -0.3% (s = 12.0%), respectively.
      CONCLUSIONS: Literature references show that the continuous thermodilution method
      is not only valid for intensive-care long-term measurement of cardiac output with
      approximately stationary haemodynamics, but also-as our results prove-valid if
      haemodynamics are not usually stationary, such as during coronary artery bypass
      surgery. The pros of the continuous thermodilution method are that no additional
      equipment is required apart from the standard equipment used in intensive-care
      medicine and cardio-anaesthesiology: that there is no stress caused by volume;
      and that manipulation is safe because no calibration routine is needed and also
      because measurement and analysis techniques are fully automated. Hence, we are of
      the opinion that the intraoperative use of this cardiac output measurement
      technique during open heart surgery is clinically indicated.

PMID- 9289021
TI  - [Calculation of lavage volume in transurethral prostate resection (TURP)].
AB  - PURPOSE: Evaluation of the relationship between ethanol concentration in expired
      air and the amount of absorbed irrigation fluid in patients who undergo a
      transurethral resection of the prostate. METHODS: 76 patients were evaluated in a
      prospective study. The irrigation fluid contained 1.92 w/w% of ethanol. The
      ethanol concentration in breath was measured at least every 10 minutes with a
      Alcotest 7410 (Drager) or a Biomed 3010 (Biotest). Documented values: breath
      ethanol concentration, mean arterial pressure, heart rate, haemoglobin
      concentration, serum sodium concentration, the amount of irrigation fluid, the
      time of operation, special events, therapeutic interventions. A modification of
      the Widmark formula was used for calculating the amount of absorbed irrigation
      fluid from the breath ethanol concentration. RESULTS: A rise of the ethanol level
      above 0.2/1000 was observed in 10 patients. No clinically significant difference
      in heart rate and blood pressure during surgery between the 24 patients with no
      alcohol in breath and the 10 patients with more than 0.2/1000 was observed.
      Prolonged duration of resection and greater amount of used irrigation fluid
      correlated with higher ethanol concentration in breath. During the study period
      no patient developed the clinical features of a transurethral resection syndrome.
      CONCLUSIONS: If 2 w/w% of ethanol is added to the irrigation fluid, breath
      ethanol concentration under 0.2/1000 may be considered harmless, while values
      above 0.2/1000 are predictors of massive absorption of irrigation fluid. In our
      patients, the addition of ethanol to the irrigation fluid has been a suitable and
      easy way to monitor the absorption of irrigation fluid, if the ethanol
      concentration in the breath is measured every ten minutes. If 2 w/w% of ethanol
      have been added to the irrigation fluid, the absorbed volume (E) can be estimated
      using the formula: E = 37.5 x body weight (kg) x ethanol concentration (/1000).

PMID- 9289024
TI  - [Ventilation methods with kinetic therapy].

PMID- 9289025
TI  - [Treatment strategies in intensive care of patients with severe thoracic injuries
      and lung contusions].

PMID- 9289023
TI  - [Effects of various feeding regimens in multiple trauma patients on septic
      complications and immune parameters].
AB  - OBJECTIVE: The aim of this study was to investigate the incidence of septic
      complications, the immunological changes by the course of lymphocyte subsets and
      metabolic parameters on polytraumatised patients when given nutritional support
      in form of early enteral and total parenteral nutrition. Furthermore, we looked
      for differences between a standard enteral diet and a diet supplemented with
      arginine, omega-3-fatty acids, nucleotide, and selenium. METHODS: 30
      polytraumatised patients with an Acute Physiology and Chronic Health Evaluation
      II (APACHE II)-Score > 10 points, who received nutritional support for a minimum
      of 7 days, were randomised to a "supplemented enteral group" (group 1), an
      "enteral standard group" (group 2), or a "parenteral group" (group 3). In the
      first both groups there were early enteral feeding. The patients of group 3 were
      fed isonitrogenous and isocaloric to group 2. Leucocytes, lymphocytes, CD3(+)-,
      CD4(+)-, CD3+HLA-DR(+)-, CD8(+)-, CD19(+)-subsets, natural killer-cells (CD56+)
      and metabolic parameters were measured on days 1, 3, 5, 7. RESULTS: Septic
      complications occurred in 2 patients in group 1, in 1 patient in group 2 and in 4
      patients in group 3. The total number of lymphocytes had an increase on day 7 in
      group 1 (1420/microliter) and group 2 (1620/microliter) and were higher compared
      with group 3 (1044/microliter). On day 7 T-cells (CD3+) were 1107/microliter in
      group 1, 1014/microliter in group 2 and 770/microliter in group 3, T-helper-cells
      (CD4+) rose on day 7 higher in the enteral fed groups (group 1:746/microliter,
      group 2:719/microliter) than in group 3 (570/microliter). No significant
      differences between the groups were seen by CD3+HLA-DR(+)-cells, T-suppressor
      cells (CD8+), B-cells (CD19+) and natural killer-cells (CD56). CONCLUSION: Early
      enteral nutrition seems to stabilise the immunosuppression of polytraumatised
      patients in an earlier phase. There is a consolidation of the lymphocyte counts,
      and of T(CD3+)- and T-helper-cells (CD4+). This could be the immunological
      correlate for the number of septic complications in the enteral fed groups.
      Therefore polytraumatised patients should be fed rather early enteral than
      parenteral when possible. In the initial phase after the trauma the way of
      nutritional support has more importance on the immune system as nutritional
      contents. So, in this form of studying, there is no advantage of immunonutrition.

PMID- 9289026
TI  - [Clinical concepts for differentiated ventilation].

PMID- 9289027
TI  - [Continuous axial position change in post-traumatic lung failure--preventive or
      therapeutic indications?].

PMID- 9289029
TI  - [Epidural administration of opioids in labor: pro].

PMID- 9289028
TI  - [Kinetic therapy within the scope of treating septic surgical patients].

PMID- 9289030
TI  - [Epidural administration of opioids in labor: contra].

PMID- 9289032
TI  - [Comment on Deusch et al.: Patient knowledge about anesthesia practice and
      responsibilities of the anesthetist].

PMID- 9289031
TI  - [Diagnosis and therapy of tracheal rupture after blunt thoracic trauma].
AB  - Tracheobronchial ruptures are rare but potentially lifethreatening events. We
      report on the case of a 34-year-old suicidal unrestrained car driver, who
      developed subcutaneous and mediastinal emphysema and right-sided haematothorax
      following blunt thoracic trauma. Fibreoptical inspection of the tracheobronchial
      system revealed a rupture (approximately 2 cm in length) of the pars membranacea
      of the trachea ending shortly above the carina. CT-scan confirmed the diagnosis
      of mediastinal emphysema, tracheal rupture and, in addition, left-sided pulmonary
      contusion. A repair of the tracheal tear was performed by right-sided thoracotomy
      using a double-lumen tube. The left-sided double-lumen tube was used
      postoperatively to achieve respirator ventilation with low pressure on the
      tracheal lumen and on the suture of the tracheal tear. On the other hand,
      sufficient airway pressure with PEEP for the left lung showing contusion could be
      provided, using the endobronchial tube. The postperative course was without
      complications. The patient was on respiratory support for three days due to his
      pulmonary contusion. Following final endoscopic control of the trachea he was
      discharged from the ICU one week after the trauma. The clinical and radiological
      signs of tracheobronchial ruptures are discussed (respiratory distress,
      haemoptysis, cyanosis, localised pain, hoarseness, coughing, dysphagia, stridor,
      subcutaneous emphysema and pneumothorax, tension pneumothorax, mediastinal
      emphysema). Fibreoptic bronchoscopy is the present gold standard for confirming
      the diagnosis. The surgical and anaesthesiological approach to the management of
      tracheobronchial ruptures is described reviewing the current literature.

PMID- 9289033
TI  - [Spinal anesthesia for ambulatory interventions: pro and contra].

PMID- 9289034
TI  - [The fundamentals of future radiation protection legislation].

PMID- 9289035
TI  - [Abdominothoracic large-caliber skin vein--a symptom of vena cava discontinuity].

PMID- 9289036
TI  - [The physiological pattern of lumbar intervertebral disk height].
AB  - Purpose of this study is to present a new method of quantifying objectively the
      height of all discs in lateral radiographs of the lumbar spine and of analysing
      the normal craniocaudal sequence pattern of lumbar disc heights. METHODS: The new
      parameter is the ventrally measured disc height corrected for the dependence on
      the angle of lordosis by normalisation to mean angles observed in the erect
      posture of healthy persons. To eliminate radiographic magnification, the
      corrected ventral height is related to the mean depth of the cranially adjoining
      vertebra. In this manner lumbar disc heights were objectively measured in young,
      mature and healthy persons (146 males and 65 females). The craniocaudal sequence
      pattern was analysed by mean values from all persons and by height differences of
      adjoining discs in each individual lumbar spine. RESULTS: Mean normative values
      demonstrated an increase in disc height between L1/L2 and L4/L5 and a constant or
      decreasing disc height between L4/L5 and L5/S1. However, this "physiological
      sequence of disc height in the statistical mean" was observed in only 36% of
      normal males and 55% of normal females. CONCLUSION: The radiological pattern of
      the "physiological sequence of lumbar disc height" leads to a relevant portion of
      false positive pathological results especially at L4/L5. An increase of disc
      height from L4/L5 to L5/S1 may be normal. The recognition of decreased disc
      height should be based on an abrupt change in the heights of adjoining discs and
      not on a deviation from a craniocaudal sequence pattern.

PMID- 9289037
TI  - [Spiral CT for the detection of coronary artery calcifications and the prognosis
      of coronary heart disease--a comparison with fluoroscopy and coronary
      angiography].
AB  - PURPOSE: Evaluation of clinical relevance of coronary calcifications detected by
      helical CT. Evaluation of congruence with fluoroscopy (FS) and coronary
      angiography. Comparison with studies reporting on application of ultrafast
      computed tomography. MATERIALS AND METHODS: 40 patients underwent helical CT (2
      mm slice thickness, table-feed 3 mm/s). Coronary angiography and FS were
      performed in usual technique. Stenosis and calcifications were evaluated
      semiquantitatively. RESULTS: 28 of 28 stenoses > or = 75% were detected via
      helical CT by evaluation of calcification (FS: 19). One non-detected solitary
      stenosis was calculated as 40%. FS did not detect 4 cases with 2-vessel and 3
      vessel disease each one case with 1-vessel disease, and one case with a main stem
      stenosis. Sensitivity of helical CT was 97% (FS: 66%). For the evaluation of
      stenosis III degree (> or = 75%), sensitivity was 100% (FS: 58%), specificity was
      77% (FS: 48%). CONCLUSION: Helical CT is more sensitive for haemodynamically
      relevant stenoses than FS. Helical CT is suitable as a substantial non-invasive
      diagnostic procedure in coronary heart disease. In certain cases, e.g. if the
      patient suffers from additional risks, helical CT should be done prior to
      coronary angiography. Coronary calcifications found incidentally in symptomatic
      patients at chest CT warrant further cardiological investigation.

PMID- 9289038
TI  - [The typical radiological findings and course of invasive pulmonary aspergillosis
      in the immunosuppressed patient].
AB  - PURPOSE: This retrospective study was designed to show whether invasive pulmonary
      aspergillosis, which is often difficult to diagnose by bronchoscopy or serology,
      can be diagnosed at an early stage by typical radiological findings on
      conventional radiographs or by CT, specially high resolution CT (HR-CT). PATIENTS
      AND METHODS: In 19 Patients with 20 disease episodes, 20 thorax radiographs and
      eight spiral CT examinations were performed and in four cases HR-CT was also
      available. The earliest pathological findings and the course of the disease were
      analysed and the results of the various examinations were compared. RESULTS: 90%
      of chest examinations, including CT and HR-CT, showed the following lesions as
      part of the earliest changes: round or wedge-shaped opacities or the so-called
      "halo" sign. CT or HR-CT always demonstrated more lesions than plain chest
      radiographs; 75% of lesions appeared typical and thereby contributed to the
      diagnosis. CONCLUSION: The typical radiological findings of round or wedge-shaped
      opacities and the so-called "halo" sign are additional criteria for the diagnosis
      of invasive pulmonary aspergillosis. The superiority of CT or HR-CT in the
      demonstration of pathological changes suggests that these should be used early in
      the investigation of patients who are specially at risk.

PMID- 9289039
TI  - [The significance of the arterial vascular supply of segment IV in living liver
      donation].
AB  - PURPOSE: Postoperative CT's in living liver donors were analysed retrospectively
      to examine whether atrophies of segment IV occur after procurement depending on
      arterial vascular supply. PATIENTS AND METHODS: Postoperative CT's from 19 living
      donors were retrospectively analysed. DSA of the upper abdomen had been performed
      on all donors prior to donation. RESULTS: The pre-operative DSA images
      demonstrated an arterial vascular supply of segment IV from the right hepatic
      artery in 10/19 cases, from the left hepatic artery in 7/19 cases and from both,
      left and right hepatic artery, in 2/19 cases. Atrophies were seen in 3/7 patients
      in which segment IV was perfused via left hepatic artery, in further two patients
      with perfusion from the right hepatic artery or from both sides respectively.
      Clinically only one patient presented with an abscess. CONCLUSIONS: The patterns
      of vascular supply to segment IV seen in our patients differ from those published
      by Couinaud. Since only 3/7 patients with an arterial supply from the left
      hepatic artery developed a segmental atrophy, we conclude that there must be
      additional, radiologically not identifiable portal venous branches or collaterals
      from the right portal vein that maintain perfusion of segment IV.

PMID- 9289040
TI  - [The intracavitary administration of contrast medium in the aftercare of
      complicated thoracic empyema with long-term drainage: x-ray fluoroscopy compared
      to computed tomography].
AB  - PURPOSE: To define the value of conventional radiography compared with CT in the
      follow-up of complicated, long-term tube drained pleural empyema after
      intracavitary application of contrast medium. METHODS: 28 patients with
      complicated pleural empyema (stage III) and long-term tube drainage were
      submitted to fluoroscopy of the pleural cavity and a CT of the thorax after
      contrast medium had been instilled into the pleural space. Both examinations were
      judged by the following criteria: number and morphology of pleural cavities,
      quality of drainage and accompanying thoracic disease. RESULTS: 49 pleural
      cavities were diagnosed. Judgement of drainage corresponded in 79% of cases and
      differed in 21% with proof of further not drained cavities only on CT. 4
      bronchopleural fistulas were diagnosed by fluoroscopy, of which only 2 were
      evident on CT. Accompanying thoracic disease was reliably detected by CT only.
      CONCLUSIONS: Diagnosis of bronchopleural fistulas and judgement of the pleural
      drainage is best possible using fluoroscopy after application of contrast medium
      into the pleural space. CT is most accurate to detect further cavities that have
      not been drained, to look for concomitant thoracic disease, and to judge the
      morphology of the pleural cavity. Conventional radiography of the pleural space
      is effective and recommended to be used as a first line investigation for the
      follow-up of stage III empyemas. Patients in poor general condition (fever,
      elevated blood markers indicating inflammation) should be examined by both
      fluoroscopy and CT.

PMID- 9289041
TI  - [Can digital selenium-based radiography in thoracic diagnosis replace the analog
      x-ray imaging technic?].
AB  - PURPOSE: To find out the diagnostic value of digital selenium radiography, we
      compared the image quality of chest x-ray images from 50 patients who had been
      examined via conventional chest x-ray and digital selenium radiography of the
      chest. METHOD: 50 patients with a malignant melanoma underwent chest x-ray within
      3 months in conventional technique and with digital selenium radiography
      (Thoravision: Philips Medical Systems, Hamburg, Germany). In this period none of
      the patients showed a difference in respect of clinical status or radiological
      diagnosis. Simultaneous examinations on the same day were not performed to avoid
      unnecessary exposure to x-rays. The digital and conventional images were compared
      by 4 radiologists with regard to image quality by the detection of defined
      anatomic structures. RESULTS: Image quality of digital selenium radiography was
      considered superior to that of conventional chest x-rays in the mediastinum, the
      retrocardiac and retrodiaphragmatic areas, the superior and inferior lobes of the
      lung especially near the parietal pleura, and the chest wall. CONCLUSIONS:
      Compared to analogous techniques there is no loss of image information when
      employing digital selenium radiography in chest x-rays. On the contrary, new
      assessment criteria may be gained. We conclude that digital selenium radiography
      offers diagnostic advantages in chest x-ray examination.

PMID- 9289042
TI  - [Indirect MR arthrography in the diagnosis of lesions of the labrum glenoidale].
AB  - PURPOSE: It has been shown that intravenous administration of contrast media
      produces an MR arthrographic effect without the need for intraarticular
      injection. This is the first study evaluating this new technique of indirect MR
      arthrography in the diagnosis of glenoid labrum tears. METHODS: 28 patients with
      clinically suspected labral injuries were prospectively investigated (1.5 Tesla,
      flexible surface coil). A plain MR examination of the shoulder (transverse and
      oblique-coronal orientation, T1-weighted spin- [TE/TR 15/675], proton density-
      and T2*-weighted gradient echo [TE/TR/Flip 14,32/600/30 degrees] sequences) and
      indirect MR arthrography (transverse and oblique-coronal orientation, fat
      suppressed T1-weighted spin-echo sequences [TE/TR 15/675], intravenous injection
      of gadopentetate dimeglumine [0.1 mmol/kg], followed by 10-15 min of joint
      movement) were performed. Results were confirmed by arthroscopy and/or open
      surgery. RESULTS: Indirect MR arthrography significantly improved delineation of
      the glenoid labrum and hyaline cartilage (p < 0.05). Sensitivity and specificity
      of indirect MR arthrography in the diagnosis of labral injuries were 90% and 89%,
      compared to 79% and 67% of the native MR examination. CONCLUSION: Indirect MR
      arthrography is a promising non-invasive technique in the evaluation of the
      glenoid labrum.

PMID- 9289043
TI  - [Magnetic resonance tomography in the diagnosis of mandibular osteomyelitis].
AB  - PURPOSE: A prospective study of the value of MRI in the diagnosis of
      osteomyelitis of the mandible with special reference to the suitability of
      different MR sequences. MATERIAL AND METHODS: In 13 patients, average age 55
      years (12-82), with clinical suspicion of osteomyelitis of the mandible, 18 MRI
      examinations were carried out (STIR, TSE T2, proton and SE T1 weighted scans with
      and without contrast, slice thickness 3.5 to 6 mm). Image quality of the
      sequences was evaluated as well as the suitability of the various sequences for
      showing the lesion, its location and extent. Activity of the osteomyelitis was
      judged by the degree of contrast uptake and was correlated with 3-phase bone
      scintigraphy and with histological findings. RESULTS: In 9 of the 14 cases the
      findings on MRI and of the scintigraphy agreed with the histology. In two
      patients the activity of the inflammatory process was exaggerated by the MRI. In
      another follow-up examination it was slightly underestimated. All lesions were
      shown to be highly active by the histology were recognized as such by MRI. For
      the localisation and recognition of the extent of the inflammatory processes STIR
      sequences and T1 weighted non-enhanced SE sequences proved the most suitable.
      Contrast medium is essential to evaluate the inflammatory activity. CONCLUSION:
      MRI is a sensitive diagnostic method; it is as good as 3-phase bone scintigraphy
      in demonstrating osteomyelitis of the mandible and of its activity but is
      superior for showing the pathological anatomy.

PMID- 9289044
TI  - [MRI dacryocystography after applying gadolinium-containing eyedrops].
AB  - PURPOSE: To determine the efficacy of MRI for the lacrimal drainage system after
      conjunctival application of gadolinium-DTPA solution. MATERIAL AND METHODS: MRI
      dacryocystography of 32 nasolacrimal duct systems was performed in 16 patients
      additional to digital subtraction dacryocystography. The gadolinium solution was
      prepared by diluting the commercially available gadolinium-DTPA (Magnevist,
      Schering AG, Berlin) 1:10 in sterile saline solution. 3 x 2 drops of this
      contrast medium were instilled bilaterally immediately before MRI scanning.
      RESULTS: MRI dacryocystography provided detailed information on the nasolacrimal
      duct system in all 32 cases. In 16 cases localisation and functional degree of
      nasolacrimal duct obstruction or stenosis was determined reliably. In 15 cases
      normal nasolacrimal duct system showed no contrast enhancement. In one case
      stenosis of the canaliculus was observed. CONCLUSION: MRI dacryocystography
      provides detailed morphological soft tissue information of the lacrimal drainage
      system. Local conjunctival application of gadolinium solution allows functional
      tests of the lacrimal duct system in patients suffering from epiphora.

PMID- 9289045
TI  - [31P-MR spectroscopy of the human liver--the spectral indications of lymphoma
      infiltration].
AB  - PURPOSE: To evaluate whether phosphorus magnetic resonance spectroscopy (31P-MRS)
      enables a non-invasive detection of liver involvement in systemic diseases like
      Hodgkin's lymphoma. MATERIALS AND METHODS: Using a clinical 1.5 Tesla whole-body
      MR system image-guided localised phosphorus MR spectra from the anatomically
      defined volumes of interests were measured. A combination of surface coil,
      adiabatic excitation pulse and modified image-selected in vivo spectroscopy
      (ISIS)-sequence was applied. The spectroscopy data were evaluated quantitatively
      with a time-domain fit programme using non-linear optimisation algorithms to
      quantify peak areas. After establishment of the examination protocol, 22 healthy
      volunteers and 13 patients with suspected lymphoma infiltration of the liver were
      examined. RESULTS: Liver spectra of patients suffering from lymphoma infiltration
      differed significantly from spectra of persons with normal liver: 1. The peak
      area ratio of phosphomonoesters (PME) to beta-NTP was elevated in all patients
      with histologically confirmed liver lymphoma. 2. Patients suffering from
      Hodgkin's disease with specific or unspecific liver infiltration (n = 7) could be
      differentiated from patients without liver involvement. In case of infiltrated
      liver, the peak area ratio PME to beta-NTP was increased, and the pH value was
      shifted to lower values. Unambiguous differentiation between non-specific (n = 3)
      and specific (n = 4) infiltration of the liver was not possible. 3. In patients
      after cytostatic treatment (n = 3), an increase of the peak area ratio of
      inorganic phosphate to beta-NTP was observed. CONCLUSIONS: Our preliminary
      results indicate that 31P-MRS can yield pointers to liver involvement in patients
      with systemic diseases such as Hodgkin's disease, which may be hardly detected by
      imaging methods.

PMID- 9289046
TI  - [Digital subtraction angiography with carbon dioxide using a new gas dosage
      system].
AB  - PURPOSE: The clinical evaluation of digital subtraction angiography with carbon
      dioxide using a newly developed low-tech CO2 dosage and injection system. METHOD
      AND PATIENTS: The hand-held system (CO2 angio set) consists of a dosage chamber
      in connection with a special stopcock to apportion the gas. By optimising
      injection volume and pressure steady gas flow characteristics are approximated. A
      safety design prevents unintentional gas injection. CO2 arteriographies were
      performed on 185 patients. Main indications were renal insufficiency and a
      history of adverse reactions to iodinated contrast media. In patients with
      femoral cannula access, catheterless reflux angiography was performed. RESULTS:
      The injection system provided complete and coherent visualisation of the
      abdominal aorta, visceral, pelvic, and lower limb arteries via catheter (71
      cases) or via femoral cannula using reflux technique (114 cases). Stenoses,
      occlusions, and collaterals were assessable. Employing the gas reflux over the
      aortic bifurcation bilateral run-off studies up to the calf trifurcation were
      performed via unilateral femoral cannula. Use of a dedicated stacking software
      improved image quality of distal femoral, popliteal and calf arteries.
      CONCLUSION: The CO2 management system allows adequate imaging of the arteries
      below the diaphragm. Ease and safety of use and low costs are advantageous.

PMID- 9289047
TI  - [The diagnosis of deep venous thromboses of the leg using a new rapid test
      (SimpliRED)].
AB  - PURPOSE: Evaluation of sensitivity and specificity of a bed-side test in the
      diagnosis of deep-vein thrombosis compared to contrast phlebography. METHODS: 122
      patients, referred for phlebography, underwent bedside testing (SimpliRED) for
      detection of deep vein thrombosis. Contrast phlebography was confirmed
      immediately afterwards. SimpliRED provides a clearly visible agglutination of the
      patient's red blood cells in the presence of elevated levels of crosslinked
      fibrin derivatives (D-dimer) in the sample, being specific for fibrin breakdown.
      RESULTS: In 37 (30.3%) patients deep vein thrombosis could be confirmed. An
      abnormal D-dimer test was found in 35 of the 37 patients with thrombosis
      (sensitivity: 94.6%). Two patients who had not been identified by agglutinin
      testing, showed an isolated calf thrombosis in small muscle veins (< 2 cm in
      diameter) not requiring treatment. 55 of 85 patients without thrombosis in
      phlebography were stated correctly by SimpliRED (specificity: 64.7%). CONCLUSION:
      All thrombotic disorders in the leg with the need for 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 such patients where the D-dimer test is abnormal. A
      false positive result of the bed-side test may be non-specific or due to elevated
      levels of fibrin split products, if the coagulation system is activated in
      several other conditions.

PMID- 9289048
TI  - [Sutureless vascular end-to-side anastomosis: an in-vivo test of a percutaneous
      concept in the animal model].
AB  - PURPOSE: To test a percutaneous concept for creation of a sutureless
      terminolateral vascular anastomosis in vivo. MATERIAL AND METHOD: By creating
      sideholes into the middle portion of a stent and a stent graft, both implants
      could be arranged in a Y-shaped configuration. An arteriovenous shunt was created
      in 3 sheep between the left carotid artery and the left external jugular vein. A
      stent graft was partially inserted into the venous lumen. Axial venous patency
      was restored by placing a stent through the sidehole into the graft lumen from an
      upstream puncture site. Graft patency was maintained by placing the sidehole of
      the stent at the bridging point between stent graft and stent with no stent
      struts crossing. Arterial end-to-end anastomosis was performed by retrograde
      placement of a stent graft into the arterial lumen. Both anastomoses were
      connected by a silicone tube. RESULTS: In all cases, a venous end-to-side
      anastomosis was created that was blood-tight and safely secured into the vascular
      lumen. CONCLUSION: Y-shaped configuration of stent and stent grafts through
      sideholes allows creation of sutureless end-to-side anastomoses in vivo.

PMID- 9289050
TI  - [Flow direction-sensitive spin-echo MR angiography].
AB  - New blood pool contrast agents yield a significant shortening of T1 of blood.
      Consequently, the usual techniques of time-of-flight and phase-contrast
      angiographies cannot produce angiograms sensitive to one flow direction, even if
      saturation slabs are applied. It was our aim to test the hypothesis of displaying
      arterial and venous flow selectively with a specially designed spin echo sequence
      even after administration of contrast agents. Parallel slice selective 90-degree
      and 180-degree pulses were applied. The distance between slices could be varied.
      It was attempted to obtain MR angiographies that were flow sensitive for one
      direction only. We performed flow phantom studies without the use of contrast
      media and first in vivo experiments in pigs after administration of iron oxide
      particles. With our modified spin echo sequence unidirectional flow can be
      displayed, whereas stationary tissue is totally suppressed. There are no special
      demands for the hardware and no additional postprocessing needs to be performed.
      The locally off-centred 90-degree and 180-degree pulses are responsible for this.
      Exclusively, protons excited by the 90-degree pulse and flowing into the slice of
      the 180-degree pulse will be refocused and only such protons will give rise to
      signal in the images.

PMID- 9289049
TI  - [2-phase contrast for the CT imaging of fistulae].
AB  - To improve the diagnosis of fistulas in CT by using a new method. 68 CT
      examination of fistulas from 1990 to 1995 were evaluated retrospectively. The
      examinations were performed in two phases: The regions of interest were scanned
      as usual, in the case of abdominal fistulas after filling the bowels with
      contrast medium. In the second phase, the fistulas were filled with highly
      concentrated contrast medium and re-examined. The presentation of this
      examination was carried out in a wide window and a high centre. In 59 of the 68
      cases the fistula and a communication with an organ or an abscess was found, in 9
      cases only the fistulous tract. The fistula and its surrounding structures can be
      well defined each with a different and individual density. By means of the chosen
      method the different density readings are visualised. Therefore, the 2-phase
      contrast method can improve fistula diagnosis by using CT.

PMID- 9289051
TI  - [The staging of rectal tumors with endorectal study technics: the demonstration
      of a possible source of error].

PMID- 9289219
TI  - Festschrift in honor of Dr. Robert L. Brent.

PMID- 9289220
TI  - [The dilemma of effectiveness and economic value of alternative medicine].
AB  - Medical practice is today, and has always been, subject to a professional ethos
      that excludes unnecessary and dishonest methods. There is some concern about
      soundness and affordability of our health service if one sees that despite the
      financial worries that beset our health services, more and more alternative
      treatments are being proposed and used which are not equal to their money's
      worth. Political and legal decisions, as well as the activities of alternative
      healers, illustrate the onslaught on the supremacy of scientific teaching. These
      developments must be opposed vigorously for sake of protecting our patients.

PMID- 9289052
TI  - [Methanol poisoning with bilateral necrosis of the putamen and additional
      involvement of the globus pallidus].

PMID- 9289221
TI  - [Social medicine evaluation of pre-employment medical screening of civil service
      candidates].
AB  - The findings and resulting number of rejections from 9.043 medical examinations
      of candidates for posts as civil servants in 1994 in Bavaria and a retrospective
      evaluation of 500 examinations at two large public health departments in Bavaria
      were used to discuss the value of such examinations and present possible
      alternatives. The rate of rejections for medical reasons in the 9.043
      examinations of civil servants starting new jobs in Bavaria was 0.57%. The most
      frequent reason for rejection was obesity. In the retrospective evaluation of 500
      medical examinations of candidates starting new jobs there were no cases of final
      rejection for medical reasons. In 0.4% of cases (n = 2) the candidates were
      considered suitable for the probationary period before becoming a civil servant,
      but unsuitable for health reasons for a life-time post in the civil service. In
      27% of cases the findings were normal without any diagnosis stated in the
      examination report. The most frequent diagnoses were refractive ametropia (55.8%)
      and changes in the locomotor system (22.2%), in particular deviation of the axis
      are vertebral column (17.6%). The results are comparable with those obtained in
      studies carried out in Europe, although the procedures and study designs
      differed. Even with a low number of rejections of around 0.5%, examinations of
      the candidates economically justified for the employer (the state). In view of
      the high number of civil servants taking early retirement, the sensitivity and
      specificity of the medical examinations before starting work are discussed, as
      well as possible and better alternatives to a single examination. One suggestion
      is continuous monitoring of all civil servants by a physician specialised in
      occupational medicine, although in particular for teachers and office workers no
      standards have been developed for the scope and frequency of occupational-medical
      health checks and consultation.

PMID- 9289222
TI  - [Social rehabilitation in day care facilities for psychiatrically ill and
      handicapped patients--results of a concomitant study of a model program by the
      Rhine-Land District Group].
AB  - Within the extension of new services for mentally ill and disabled peoples
      outside of inpatient settings, the Landschaftsverband Rheinland (LVR) decided in
      1990 to finance day care facilities especially for those patients who could
      previously not be integrated in the existing community psychiatry service
      structure due to the severity of their illness or handicap. A cost reducing
      effect in the clinical and residential service area was also intended. The first
      ten of these facilities were included in a 2-year research project. This report
      includes findings in various sectors: characteristics of the user group,
      functions and focal points of care, association with other community psychiatry
      services, cost effectiveness, and user opinions. Most visitors experienced a
      stabilisation of their personal situation and improvement of their quality of
      life. The average length of hospital stays was reduced from 102 to 25 days per
      year. The hopes accompanied with the programme were only partially fulfilled;
      possible consequences are discussed.

PMID- 9289223
TI  - [Calculation of mortality tables and trends longevity figures for the Saxony
      population 1980 to 1994].
AB  - Basing on the population figures and deaths between 1980 to 1994, we calculated
      mortality tables for the Grman province (or "Free State", as 1st is called) of
      Saxony. The method for calculating the period mortality tables according to
      Becker, Zeuner based on the year of dying, was modified for small parent
      populations (correction of baby mortality according to Rahts, smoothing
      algorithm). The influence exercised by baby mortality and migration on life
      expectancy is shown. Estimated errors of the model are calculated for the first
      time (maximum absolute deviation for eo scatter, 95% confidence interval for eo).
      Presentation of different lifespan data proves that the positive trend of the
      life prolongation process is continuing. For example, the life expectancy of male
      newborn increased during the observation period by 1.94 years (from 69.38 to
      71.31 years), that of female newborn by 3.50 years (from 75.2 to 78.62). Women
      increased their lead in life expectancy against men by 1.56 years (from 5.75 to
      7.31 years). The reduction in baby morality and in the standardised mortality
      rate are other favourable factors. These figures dropped during the observation
      period from M: 12.0 on 7.0 and from F: 8.9 on 4.8, respectively from M: 14.4 on
      1.0 and F: 13.3 on 12.7 per 1000 of the population.

PMID- 9289225
TI  - [Frankfurt Vaccination Intervention Study--Friva].
AB  - The success of the recommendation of vaccinations on the occasion of school
      beginner examinations is assessed. The feedback rate of the intervention group
      amounts to 65%. The recommended vaccinations were carried out at 60% (measles
      mumps-rubella) up to 90% (tetanus).

PMID- 9289224
TI  - [Non- and low-response after preventive hepatitis B vaccination].
AB  - 20 years after the introduction of the hepatitis-B vaccine the question still
      remains unsolved as to how the 2 to 5 per cent of the vaccinees who, after basic
      immunisation, respond with no anti-HBs levels (0-10 IU/l nonresponder, NR) or low
      levels (11-99 IU/l low-responder, LR) should be boostered to acquire sufficient
      and long-lasting protective anti-HBs levels. In a retrospective analysis of
      booster results we found in 75 NR and LR that the probability for long-lasting
      protection is very low for NR, but better for LR (60%). In a second part of this
      publication, the efficacy of intradermal and intramuscular hepatitis-B boosters
      was examined by retrospective analysis of booster results among 26 NR and LR. A
      slight advantage of the intradermal application was found concerning post-booster
      anti-HBs increase and the maximal HBs values reached. Long-lasting protective
      anti-HBs values could not be established for either way of application. Finally,
      a survey of the literature summing up true results of intradermal hepatitis-B
      basic immunisations with reduced doses (mostly 2 micrograms), shows that whereas
      the seroconversion rates achieved by this method are almost compatible with those
      after regular basic vaccination, the GMT values were far lower than those after
      regular basic vaccination. Prospective and randomised studies are needed to show
      which kind of booster is most efficient for nonresponders and low-responders.

PMID- 9289226
TI  - [What is the current age and sex-related cadmium burden of the human kidney
      cortex?].
AB  - 55 persons of either sex in the age bracket between 0.02 and 87 years had to be
      examined by experts in forensic medicine. In these examinations, slices of kidney
      cortex were removed and prepared for cadmium(Cd)-determination by atomic
      absorption spectrophotometry. The samples were wet ashed by a special and quick
      method developed in our laboratory, using concentrated (65%) HNO3 for a short
      period of 1 hour at 90 degrees C. The main results of the present study were that
      Cd accumulation in the kidney cortex was delayed in the age group between 0.02
      and 40 years. The highest Cd concentration of 27 micrograms/g wet weight was
      found in the age group between 50-59 years. In persons of higher age, above 60
      years, the Cd concentrations were generally lower than in persons of the age
      group between 50-59 years; however, this decline does not seem to be significant.
      Summing up, we can say that the delayed increase in Cd concentrations in the
      kidney cortex of persons in the age group between 0.02 and 40 years might be
      regarded as the first positive result of the restrictive use of Cd materials,
      resulting in food intake with lower Cd contamination. The present study should be
      repeated after about 5 years to confirm whether this hopeful assumption is true.

PMID- 9289228
TI  - [Understanding and motivation: 10 primary responsibilities for public health].

PMID- 9289227
TI  - [Limits of optimizing resource allocation by debiting the public health service].
AB  - Based on the Dornier consulting opinion on the public health service system of
      Berlin, the limits of optimising the resource allocation process are discussed
      with respect to austerity budgets. The discussion focuses firstly on problems of
      finding a consensus of opinion about public tasks and purposes in the German
      settings of pluralistic impact on health policy, and secondly on methodical,
      functional and practical limits. Methodical arguments are supported by a
      comparison of personal density with regard to the twelve largest cities of
      Western Germany, and supplemented by a factor analysis of sociodemographic
      characteristics in order to quantify the need of social work in an urban context.
      Functional and practical limits are demonstrated with respect to the realisation
      of the principle of subsidiary and concerning the practice of wholesale cut-downs
      of public health services budget.

PMID- 9289229
TI  - [Tradition and future with reference to an academy].

PMID- 9289230
TI  - [A comparative study of pulmonary elasticity and diffusion through the
      alveolocapillary membrane in major collagenoses with lung involvement].
AB  - We studied 60 patients with collagen-vascular diseases with pulmonary
      manifestations (SLE-25; SSc-13; mixed connective tissue disease-12; RA-6; PD-DM
      3; ankylosing spondylitis-1), 54 females and 6 males, mean age 42.4 +/- 9.9
      years. We measured lung volumes (total lung capacity-TLC) by spirography
      (Flowscreen Jaeger) and body plethysmography (Bodyplethismograph Jaeger);
      compliance of the lungs (CL) and elastic recoil pressures at 100%, 80% and 70%
      TLC (PL,el 100%, 80%, 70% TLC) by the esophageal catheter method; diffusing
      capacity of the lungs by the single-breath method (DL,COSB) (Alveo-Diffusionstest
      Jaeger). DL,CO was diminished in 45 (75%) of cases. 11 patients (18.3%) had an
      increased elastic recoil, equally distributed between mild and severe decrease of
      DL,CO. Statistical significant correlations were found between TLC-DL,CO (r =
      0.63; p < 0.001) and TL-CL (r = 0.49; p < 0.001). No correlations were found
      between DL,CO and PL,el 100, 80, 70% TLC. The results are expressed as percent of
      predicted value (% pred.). The mean values and standard deviation (X +/- sd) were
      calculated. CONCLUSIONS: I) DL,CO is the most frequent altered pulmonary function
      test in collagen-vascular diseases with pulmonary manifestations; it seems to be
      a sensible parameter for diagnosing these diseases. 2) The alteration of DL,CO,CL
      and PL,el appears to be rather as a result of "shrinking lungs" due to
      respiratory muscle involvement than to an interstitial lung disease. 3) Elastic
      recoil pressures and compliance should be considered as routine pulmonary
      function test, important for the evaluation of treatment and prognosis.

PMID- 9289231
TI  - [The comparative results of the antibiograms for Mycobacterium tuberculosis
      performed in 2 different laboratories].
AB  - The aim of this study was to appreciate the accuracy of the technique for
      sensitivity test for M. tuberculosis. We have tested the same bacterial strains
      (101) using the same drugs concentrations, by absolute concentration method, and
      we have compared the results obtained in two different laboratories. The
      concordance of the obtained results (94.05% for SM, 97.03% for INH, 99.01% for
      RMP, 100% for EMB) is in the limits of reproducibility obtained by other authors.
      The obtained results show a good technique for sensitivity test in the two
      laboratories.

PMID- 9289232
TI  - [The diagnostic and treatment aspects in bronchopulmonary neoplasms in Dolj
      County].
AB  - The study carried out during 1991-1995 concerns 50 subjects with lung cancer
      confirmed by microscopy registered in the Oncology Department of Craiova
      University Hospital. The patients were studied on terms of clinical stage which
      indicated the regime of treatment associations: surgery + chemotherapy +
      radiotherapy, chemo-radiotherapy, chemo-immunotherapy, in order to improve
      surviving. The treatment results were assayed for each group of patients
      according to the international criteria of treatment response evaluation. The
      efficiency of various cytostatics associations according to histopathologic form
      was finally evaluated on terms of asymptomatic period and survival duration.

PMID- 9289233
TI  - [Single-dose administration in the treatment with penicillin G (PG) and
      metronidazole (Me) in primary pulmonary abscesses (a preliminary study)].
AB  - The anaerobic bacteria play the main role in the etiology of the lung abscesses
      (Finegold, 1989). From this reason, the administration of the association PG and
      Me (endovenously or per os) gives a high healing rate in our country; 90.5%. The
      objective of this work was to study the influence of the drug-administration
      rhythm on the therapeutical results. The drugs were given once daily, several
      times daily, or in a combination of those 2 modalities. A lot of 38 patients
      hospitalized between 1.01.94-31.12.95 in the Institute of Pneumophthisiology, was
      divided in 3 groups: U (11 cases--28.9%), treated with PG: 5-10 mill and Me: 1.5
      2 g in one endovenous perfusion, daily: M (18 cases--47.3%), treated with PG: 5
      10 mill, one endovenous perfusion daily and Me: 1.5-2 g, 2-4 times daily: F (9
      cases--23.8%), treated with both PG: 5-10 mill and Me: 1.5-2 g, 2-4 times daily.
      Cases with lung abscess and advanced neoplasia, hepato-renal or cardio-pulmonary
      insufficiencies, were excluded. The hospitalization period was 15-77 days, with
      an average of 38.3 +/- 26. The proportion of the therapeutical successes,
      estimated as the disparition of the clinical suppurative symptomatology and the
      reduction > or = 90% of the lesions and cavity surfaces on the chest X-ray, was
      for the group U: 90.9% (10 from 11 cases), for M: 94.4% (17 from 18 cases) and
      for F: 88.9% (8 from 9 cases), the difference being statistical non-significant.

PMID- 9289234
TI  - [An evaluation of the identification technics with IS6110 and Mt308 used as
      molecular markers for Mycobacterium tuberculosis strains isolated in Romania].
AB  - During the past years, new diagnostic technologies based on DNA methods including
      PCR, were developed in the aid of tuberculosis control. Among several DNA
      sequences, an insertion sequence IS6110, found to be specific to mycobacteria
      belonging to M. tuberculosis complex were used. However, recent studies showed
      the absence of this IS6110 in 3-4% of M. tuberculosis strains isolated from
      patients of Vietnamese origin. In order to evaluate the frequency of IS6110 among
      a series of strains isolated in Romania, we have performed the PCR technique for
      amplification of 2 DNA specific regions of M. tuberculosis complex. The sequences
      of primers were as shown before (Guesdon et al., 1990). For this study, 219
      strains have been isolated from tuberculous patients, in "Marius Nasta" Institute
      of Bucharest, Romania. We have shown that genomic DNA from 3.6% of 219 strains
      evaluated in our study do not contain the IS6110 sequence and could determine
      some identification problems when this molecular sequence is targeted.

PMID- 9289235
TI  - [Pulmonary complications during HIV infection in children].

PMID- 9289236
TI  - [Cough--its neurophysiological mechanism, phases and sound].

PMID- 9289238
TI  - [The therapeutic and diagnostic contribution of ceftazidime (Fortum) in
      Pseudomonas aeruginosa superinfection in a patient with chronic bronchopathy].

PMID- 9289239
TI  - [Adhesion molecules and their role in bronchial asthma].

PMID- 9289237
TI  - [The plurality of risk factors in a case of right-sided pneumonectomy].
AB  - A right lung cancer case is presented, aged 65 years, obese, submitted to a right
      lung resection. Stress is laid on the difficult evolution concerning the
      haemodynamics and particularly the breathing owing to the association of risk
      factors.

PMID- 9289241
TI  - [The epidemiological aspects of tobacco use disorder in Europe].

PMID- 9289240
TI  - [Fluticasone propionate--a new name common in asthma and rhinitis].

PMID- 9289242
TI  - [The 25th National Conference of Pneumophthisiology, 17-18 October 1996, Poiana
      Brasov. Roundtable: care in chronic obstructive bronchopulmonary diseases].

PMID- 9289244
TI  - [The progress of malaria in sahelian eastern Niger. An ecological disaster zone].
AB  - The south eastern part of the Republic of Niger was ecologically damaged by the
      dryness since 1971. Rainfall decreased by 30 to 40% as compared to 1961-70 and
      lake Chad retreated 100 km to the south. Now it does not reach any more the
      Republic of Niger. Malaria studies have been carried out in urban and suburban
      places in Zinder and in the Diffa area at the extreme east. In Zinder parasitic
      indexes (PI) after the rainy season were around 30% to 10% according to the
      situation of the corner in respect with surface waters during the rains. In dry
      season the index fell to 3%. In Diffa in a part of the city at high risk because
      lining the Komadougou river, PI was only 6.7% in October after the rains. Before
      1970 PI recorded in Niamey were up to 50%. In Diffa area they were of 49% in
      N'Guigmi and 32% in Bosso, ecologically similar to Diffa. Obviously there was a
      sharp decrease of malaria which could be due to the disappearance of An. funestus
      after 1970. It was one of the main malaria vectors. Its larvae were developing in
      pools remaining after the rains with heavy standing vegetation. These breeding
      sites have been destroyed by both dryness and human activities. Now the area has
      became hypoendemic and is suitable for epidemic because population has not much
      immunity. A surveillance system for epidemic control should be settle.

PMID- 9289243
TI  - [The tuberculosis endemic and its control in the city of Bucharest in 1996].
AB  - Tuberculosis is one of the main problems of public health and the population has
      to face it in one of the biggest crowded town in Romania, Bucharest. It is also
      the capital of the country. An increasing tendency has appeared in the number of
      cases and deaths due to tuberculosis. The overall incidence of tuberculosis has
      increased by 5% in 1996, attaining finally the level of 128.6/100,000. The level
      is exceeded only by a few towns in Romania. The increase is due almost
      exclusively to the new cases of disease. The program of chemotherapy is facing a
      more reduced rate of cure and, implicitly, a high rate of failure by treatment.
      The periodical prevalence of the bacilliferous patients has attained
      129.0/100,000 inhabitants. The deaths by tuberculosis have been increasing for a
      few years; the mortality was of 13.6/100,000 inhabitants in 1995 more than double
      as that in 1995 (6.5/100,000).

PMID- 9289245
TI  - [Blood levels of protein markers of inflammation and nutrition in the meningo
      encephalitis phase of human African trypanosomiasis].
AB  - Two acute phase proteins; C-reactive protein and acid alpha 1-glycoprotein and
      three nutritional markers; prealbumin, retinol binding protein and transferrin
      have been evaluated in 8 patients suffering from trypanosomiasis in
      meningoencephalitic state and compared to those obtained from 15 normal control
      subjects. Findings show a markly decrease of nutritional markers without change
      of sera acute phase proteins. We concluded that in meningo-encephalitic state of
      human african trypanosomiasis, denutrition was a major biological or clinical
      feature in association with lymphoid cells stimulation as revealed by beta 2-M
      levels.

PMID- 9289246
TI  - [Endemic disease and clinical manifestations of onchocerciasis in the province of
      Rutana (Burundi)].
AB  - In 9 'collines' (administrative units) of the province of Rutana (Burundi) a
      sample of the population was examined to determine the prevalence and intensity
      of onchocerciasis in this endemic region. In all, the area is hypoendemic with
      7.9% of the population infected. This means that, in a population of 52,000,
      about 4000 persons are parasitised. The intensity of onchocerciasis is low, in
      general. Clinical examination in a subsample of 4 collines showed that the number
      of people with onchocerciasis who complain about pruritus or who have skin
      lesions is limited (respectively 54.4% and 38.1%). Subcutaneous nodules are small
      and difficult to detect (20.6% in positive persons). Ocular damage, as measured
      by visual acuity, is minimal: 89.9% of the examined eyes had a visual acuity of
      10/10. Amongst positive persons, 23.6% had a slightly deteriorated vision
      (between 9/10 and 3/10) which might be attributed to onchocerciasis.

PMID- 9289247
TI  - [Acquired recto-vaginal fistula in children: is HIV infection a cause?].
AB  - Seven successive cases of acquired rectovaginal fistula have been diagnosed on
      children of three and half to eighteen months old. These fistula were localised
      on the fourchette. The seropositivity for HIV of five cases confirmed the results
      of similar reports found in literature. Surgical treatment of these girls was not
      done because of their bad presentation. Two of these children died. The other did
      not come for follow-up. The acquired rectovaginal fistula seems to be a sign of
      HIV infection. This work is meant to emphasise the relationship between AIDS and
      acquired rectovaginal fistula for a closer surveillance of future cases.

PMID- 9289248
TI  - [Neuromyelopathy in the population of Noir-marron of Saint-Laurent du Maroni in
      French Guiana].
AB  - The neurological observations have been reported at Andre Bouron Hospital of
      Saint-Laurent du Maroni and at General Hospital of Cayenne during a period of 5
      years. All patients belonged to the "Noir Marron" ethnic group and lived in the
      area of Saint-Laurent. There were six women and four men, aged 15-35 years.
      Neurological symptoms were isolated or associated to other organ failure.
      Neurological manifestations included retrobulbar optic neuropathy, spastic
      paraparesis, sensitive ataxia and cerebellar ataxia, psychiatric symptoms were
      observed. Other organs affected were cardiovascular, digestive, cutaneous or
      endocrinologic (thyroid). Diet consist mainly in cassava. Thiamin deficiency has
      been observed several times. Improvement of neurological deficits following
      thiamin administration points towards Thiamin as an etiological factor.
      Ethnological specificity of Saint-Laurent area may explain that such neurological
      manifestation have not been observed in the rest of the department.

PMID- 9289250
TI  - [The role of Huhner's direct post-coital test in the evaluation of conjugal
      sterility in the African environment in Senegal. (Apropos of 2593 post-coital
      tests performed by the clinical cytology, cytogenetic and reproduction biology
      laboratory at the University Hospital Center in Dakar, Senegal) 1983-1993].
AB  - About 2593 post-coital tests (PCT) or Huhner direct tests were realised in the
      laboratory of clinical cytology, cytogenetics and reproductive biology of the
      University medical Centre of Dakar, Senegal from 1983 to 1993. Analysing the
      results, the authors showed the importance of the infectious factor in women and
      also the role of male deficiency in conjugal sterility in black African
      environment. These realities have been confirmed cytospermiologic test deficient
      results. These sperm exams have shown among other things, the prevailing number
      of azoospermia (25%) and of oligo-asthenoteratozoospermia (44%) in husbands of
      sterile women in the black African environment of Senegal. Pap's Tests have been
      jointly realised at the same time as 1902 PCT. The results have enabled us to
      track down 120 cervix with precancerous and cancerous cell alterations; 81
      condylomas (HPV), 25 CIN1, 11 CIN2 and 3 CIN3 (CIN: cervical intra-epithelial
      Neoplasia). These facts suggest a cautious technics, and a prudent interpretation
      of the results and taking into account the competence and the subjectivity of the
      practitioner. We have learnt from the study that we must give as much as possible
      to biologists of Reproduction in southern countries, where conjugal sterility and
      cervix precancerous and cancerous cell alterations are high, a polyvalent
      training so that they can practise jointly the post-coital or Huhner direct test
      (PCT) and the Papanicolaou Colpocytologic Test (TP), provided that one owes a
      microscope.

PMID- 9289249
TI  - [A case of acute pyrimethamine poisoning].
AB  - Intoxication by pyrimethamine is rare compare to these of patients who ingest a
      massive dose of amino-4-quinoleine. Clinic manifestations can be delayed and they
      are specially based on haematologic disorder as shown by literature data. Others
      organs can be concerned. The authors would like to present the case of a patient
      with a severe pancytopenia accompanied with: ocular blow like hyperhaemia of
      conjunctiva then iris siderosis. skin attack as Gunther's disease. Etiologic
      treatment by folinic acid is the only deduction. Recovery is complete.

PMID- 9289252
TI  - [Anopheles species and the transmission of malaria in the forest/savannah
      transition zone in central Cameroon].
AB  - A longitudinal study on malaria vectors and transmission was carried out in a
      forest-savannah transitional area in Cameroon. Indoor all night mosquito
      collections on human bait were performed during one year in two villages: Nditam
      and Ngoume. Nditam was located in a secondary forest block surrounded by
      savannah, while Ngoume was situated in an ancient forest block. The results
      showed that at Nditam, only one anopheline species was collected, that was
      Anopheles gambiae s.l.. The average daily biting rate was 2.4 bites per man per
      night. The sporozoitic index of An. gambiae was 9.4%. The entomological
      inoculation rate was therefore estimated at 0.225 infective bite per man per
      night that is to say 82 infective bites per man per year. Malaria transmission
      was low during the year, but an important increase was observed in September,
      when the rainfall was at its peak. At Ngoume, no Anopheles mosquito was
      collected. Therefore, malaria transmission was not observed in that village.

PMID- 9289251
TI  - [The results of retreatment of pulmonary tuberculosis using a short 6-month
      protocol 1985-1991 in the pneumo-phthisiology department of the Point G hospital
      in Bamako].
AB  - This study concerns 321 files of smear positive tuberculosis patients admitted in
      the pneumo-phtysiology service of Pt G Hospital for re-treatment from April 1985
      to December 1991. The re-treatment pulmonary tuberculosis with positive spits
      represent 13.3% of pulmonary tuberculosis cases and 10.1% of the whole
      tuberculosis diseases. High rate with a ratio of 3 men for a woman was found
      among men. The same conclusion was reached by SAMAKE (7). Patients age raking
      from 20 to 49 were the most affected in a proportion of 75.7%. Evolutive relapses
      were the principal reasons for re-treatment (71.2%) and take place above all
      among patient treated with the 12 months conventional regime. The conclusion
      reached corroborates those of STYBLO (8). The regime was 3RHZES3/3R3H3E3. The
      maximum of negating has been reached during the 3rd month with 93.4% rate. It has
      been during these 3 last months consolidation phase that the highest drop out has
      been noticed (17.1%). This is certainly due to the better off felt by patients.
      At the end of treatment 76.3% of the patients have recovered against 1.5% failure
      rate and 5.3% drop out. Our treatment regime, though different from those advised
      by WHO and IUATLD, is an efficient one. However in the new programme of fighting
      against tuberculosis of Mali, it has been decided to replace our treatment with
      that of WHO and IUATLD.

PMID- 9289253
TI  - [Human ecology and tropical medicine].
AB  - Tropical medicine's growing interest in social sciences has not remedied the
      neglect of some biological aspects related to human species polymorphism. These
      are adaptability to the environment and variability in time and space. Physical
      anthropology, when it is enlarged to include population genetics and the
      influence of the non-linear mode of thinking used in ecological sciences, may
      provide a good approach for solving problems related to development. Adaptability
      to a changing environment is partly cultural and partly biological. Medical
      standards used in developed countries may not be adequate in tropical regions.
      This paper reviews different areas in which human ecology can be useful to
      physicians, especially the study of the interactions between pathogens, human
      hosts, culture, and the physical environment.

PMID- 9289254
TI  - [Dehydration: an important factor of mortality in human immunodeficiency virus
      (HIV) seropositive malnourished children].
AB  - A combination of diarrhoea and malnutrition frequently occurs in HIV seropositive
      children and constitutes a bad prognosis factor. The impact of dehydration
      induced by diarrhoea in these children has not as yet been assessed and
      constitutes the aim of this study. This retrospective analysis was conducted on
      121 malnourished children monitored in 1994 at an infant home in Cote d'lvoire.
      46.2% of the children were HIV seropositive and their mortality rate was
      significantly higher than that observed among seronegative children (42.8% vs.
      15.3%; p < 0.01). Among the various pathologies observed in these children,
      diarrhoea and oral candidosis were discriminating factors in seropositive
      children. Besides, the findings confirmed the effect of dehydration on the
      mortality of malnourished children as a whole. Studies allowing a better
      understanding of factors involved in diarrhoea or dehydration among HIV
      seropositive malnourished children appears to be essential to improve the
      management of these children.

PMID- 9289256
TI  - [A case of Mycobacterium shimoidei lung infection in Madagascar].
AB  - In 1980, a 32 years-old Madagascan female developed a pulmonary tuberculosis,
      bacteriologically confirmed. She cured with right apical cavitary sequellae. In
      1989, she presented haemoptysis again. Antituberculous treatment was adopted
      without bacteriological confirmation and did not improve clinical symptoms. In
      1991 and 1992 cultures from sputa and bronchi aspiration yielded acid-fast
      bacilli identified as Mycobacterium shimoidei. M. tuberculosis could not be
      detected. The patient died during treatment. This case is the fourth one in the
      literature. Whereas previous cases have been reported in Europe, Australia, Asia,
      this new case shows M. shimoidei is also present in Africa.

PMID- 9289255
TI  - [Detection of hepatitis c in blood donors in Niamey].
AB  - We searched for HCV antibodies in a random sample of 410 blood donors negative
      for HIV infection, hepatitis B and syphilis. 16 peoples were positive by ELISA
      and 13 by RIBA. So 3.2% of these donors negative for the three actual compulsory
      tests, are able to transmit HCV.

PMID- 9289257
TI  - [Chancroid in Algeria: the status of this sexually transmitted disease in 1995].
AB  - Absent for several decades, the chancroid reappeared in Algeria in 1988. In the
      unique department of Dermatology and Venereology of the University Hospital of
      the country of Tlemcen (more than 700,000 inhabitants), we wanted to know the
      state of this STD seven years after the report of the first cases. The file of
      the consulting patients were examined. We looked for the principal
      characteristics of this STD: age, sex, incubation period, place infection
      contact, type of relation, clinical presentation, evolution without and with
      treatment, other associated STD (syphilis, HIV). From August 1988 (1st case) to
      December 1995, 144 cases of chancroid were collected = 1988: 6, 1989: 5, 1990: 7,
      1991: 18, 1992: 11, 1993: 33, 1994: 48, 1995: 16. The presentation is quite
      stereotyped; it concerns males only, singles in must cases, having had sexual
      relations with prostitutes. The incubation period is short (less than 10 days),
      the characteristic ulceration presents, very often, some adenopathies. The
      treatment by cotrimoxazole is efficient. They are no concomitant syphilis or HIV
      infection. The chancroid is the first cause of genital ulceration in the world.
      Since 1991, it is the principal STD in our department. It spreads within a male
      population, young singles associated with prostitutes. It is well installed in
      Algeria, and its role, although minor, in the transmission of the HIV infection,
      should not be neglected.

PMID- 9289258
TI  - [The microbial etiology of genital discharges in Nouakchott, Mauritania].
AB  - The survey carried on 579 patients of both sexes, consulting for genital
      discharges (spontaneous or referred), showed that in 61.1% men cases, STD agents
      were isolated (Neisseria gonorrhoeae 51.5%) and 64.4% in women cases (Gardnerella
      vaginalis 24%, Candida albicans 20%. Trichomonas vaginalis 14%). 17% of Neisseria
      gonorrhoeae strains were penicillinase-producing (PPNG).

PMID- 9289259
TI  - [In vivo chemosensitivity tests of Plasmodium falciparum to chloroquine in
      Senegal: the development of resistance and the assessment of therapeutic
      efficacy].
AB  - The efficacity of oral chloroquine was assessed in 360 out-clinic patients with
      symptomatic Plasmodium falciparum malaria who were enrolled at five sites, in
      four administrative regions of Senegal, between 1991 and 1995. They were three
      rural areas: Mlomp (Casamance), Bandafassilbel (Eastern Senegal), Diohine (Sine
      Saloum) and one urban area: Pikine (agglomeration of Dakar). Parasitological
      failure at Day-7 was observed in 108 patients (30%) and ranged from 14% to 50%
      according to the study areas. The proportion of RI, RII and RIII responses were
      6%, 23% and 1%, respectively. Chloroquine resistance was lowest in Bandafassi,
      one of the most remote area of Senegal. It was highest in Mlomp where a malaria
      control programme with mass chemoprophylaxis had been carried out since 1975. The
      therapeutic failure rate defined by the persistence or reappearance of fever and
      P. falciparum trophozoites on days 4-7 was 6%. The percentages of therapeutic
      failure for RI, RII and RIII patients were respectively 14%, 19% and 100%. These
      results and those of previous studies in Senegal suggest that chloroquine
      resistance, which first emerged in vivo in 1988 in Dakar, spread between 1990 and
      1993 in all regions of this country. The limitations of in vivo tests for the
      determination of the therapeutic efficacy of chloroquine in malaria endemic
      regions with increasing chemoresistance are discussed. The low proportion of
      potentially severe malaria infections in semi-immune persons, the biases in
      patients selection, and the possibility of delayed complications, considerably
      limit the potential of these tests for guiding the choice of the best adapted
      first line treatment.

PMID- 9289260
TI  - In vitro sensitivity of Plasmodium falciparum to anti-folinic agents
      (trimethoprim, pyrimethamine, cycloguanil): a study of 29 African strains.
AB  - The in vitro drug sensitivity of three dihydrofolate reductase inhibitors
      (pyrimethamine, cycloguanil, trimethoprim) was determined against 29 strains and
      isolates of Plasmodium falciparum by an isotopic semi-microtest. Trimethoprim is
      less active than pyrimethamine or cycloguanil and its activity is correlated with
      that of two other inhibitors, suggesting cross-resistance in vitro among the
      dihydrofolate reductase inhibitors.

PMID- 9289261
TI  - [Eco-epidemiology of malaria in Niamey and in the river valley, the Republic of
      Niger, 1992-1995].
AB  - The Niger valley is an original ecosystem in the Sahelian belt. For more than 25
      years it has been affected by dryness and rainfall decreased by more than 30% as
      compared to the period 1950-1960. Moreover the demography has sharply increased
      and the capital town Niamey grew by 10% a year. The Niger valley including Niamey
      has about 1 million inhabitants. Three sites have been selected to study the
      status of malaria and its evolution for the last 30 years: Niamey, Karma 40 km on
      the N.W. on the river and the nearby fossil valley of Fatay-Karma. In the sixties
      the malaria vectors were An. gambiae, An. arabiensis et An. funestus. The last
      species was no more harvested after 1970 because its breeding places have been
      destroyed on the combined action of dryness and human activities. In Niamey,
      parasite index was very low in the dry season but grew by 5 to 10 times during
      the rainy season to reach 50% in certain corners. The highest plasmodic index
      (PI) were recorded along the river banks where vectors are found all the year
      long. It decreases in the central part of the city and becomes very low in some
      peripheral suburban settlements. This situation is quite different of most of the
      cities of the area where prevalence decrease from outskirts to city centre. The
      serology confirms these points. In Karma, along the Niger and despite a perennial
      transmission, the PI removes low as well as the malaria antibodies, probably
      because of the self use of antimalarial drugs by the population. In Fatay-Karma
      the PI of 23.9% after the rainy season drops to 6% in the dry one. In data prior
      to 1970 the PI was over 60%, reaching 89% in young children of Niamey suburbs.
      Obviously it has strongly decreased. It is very likely that this is due partly to
      the disappearance of An. funestus after the drought.

PMID- 9289262
TI  - [Laparoscopic surgery: its value and limits. Is the conversion a failure?].

PMID- 9289263
TI  - [A minimally invasive approach in choledocholithiasis].
AB  - In the last years several less aggressive procedures diminished the role of open
      choledochotomy (CT) in the treatment of common bile duct (CBD) lithiasis. Between
      them are endoscopic sphincterotomy (EST) and laparoscopic choledochotomy. In a
      lap of 18 month were followed up, in a prospective way, all the cases of CBD
      lithiasis admitted in our department. Twenty-seven patients were treated by EST
      and 28 by CT. The endoscopy was as efficient as open CT in clearing the CBD (85%
      vs. 83%). Even if the endoscopic group was at a higher risk the morbidity was
      lower than in the classic approach and the mortality was the same (3.5%). The
      most common complication after EST was acute pancreatitis (7.5%). The mean
      hospital stay was lower after EST. Near by are discussed 3 cases of associated
      gallbladder and CBD lithiasis treated exclusively by laparoscopic approach.

PMID- 9289264
TI  - [Breast cancer in men. The clinico-therapeutic considerations].

PMID- 9289265
TI  - [Breast cancer in men].
AB  - In 20 years we registered 10 observations of male breast cancer (MBC),
      representing 1.3% out of 767 patients with breast cancer. Two observations of
      gynecomastia have been noted as a possible risk factor for MBC. A tumoral mass
      behind the areola suggested the diagnosis in 9 patients, whether in one case the
      attention was drawn by a bloody nipple discharge. In 3 cases we noted local
      aggravation clinical signs, and 6 observations presented homolateral palpable
      adenopathy. Diagnosis was completed by radiology, scintigraphy and pathology. As
      for clinical staging, we had 1 case in stage I,3 patients in stage II, 5 in stage
      III and I case in stage IV. Surgical treatment was the major therapeutical mean
      of the complex oncological procedure. We performed radical mastectomy in 4 cases.
      MBC prognosis was poor. Only one patient of the 6 ones in stage III and IV
      survived to five years; among other 4 observations in stage I and II, 2 patients
      have survived to five years, and other 2 being followed-up through the
      oncological network.

PMID- 9289266
TI  - [Early results in the treatment of colonic cancer. The case histories of Surgical
      Clinic No. 1 in Tirgu-Mures].

PMID- 9289267
TI  - [Spigelian hernias. The authors' own experience and a review of the literature].
AB  - There are presented nine patients with spigelian hernia operated on between 1964
      and 1996 (33 years interval). These patients represent 0.19% of the totality of
      the patients operated for different hernias in the same period. The sex ratio
      female/male was 7/2. The medium age of the patients was 55 years old +/- 12-18,
      the extremes being 37 and 67 years. To all the patients the hernia was located on
      the right side of the abdomen. The main associated disease, the degree III and IV
      obesity was present in 8 from 9 cases. In 3 cases (33%) the evolution was
      complicated by incarceration of the big epiploon and to one patient (11%) by
      partial strangulation of a jejunum ansae, Richter's type. Two patients with very
      large, nonreducible hernias created possibilities of confusions with abdominal
      tumors. Generally, the diagnosis was established only on clinical basis. All the
      patients were operated on (the Bachy techniques with direct approach) without
      immediate or late complications (there were no recurrences).

PMID- 9289268
TI  - [Motility deficits in Roux-loop gastrojejunal reconstruction after the surgical
      treatment of reflux diseases (the Roux stasis syndrome)].
AB  - Motor disorders due to Roux-en-Y gastrojejunostomy are not uncommon, although not
      yet fully explained. Facing Roux stasis syndrome in patients who underwent Roux
      en-Y diversion for secondary reflux pathology, we decided to study the motoric
      outcome of all 28 cases operated on for benign conditions in 1981-1996. We were
      interested only in motility disturbance related to our surgical act, so other
      therapeutic results were neglected. Since we could not perform manometric
      research and scintigraphic clearance was performed only in selected cases, our
      study was mainly clinical and based on radiology. There was no late stasis
      symptomatology in 19 patients operated for non-reflux pathology, but one third of
      refluxers developed Roux stasis syndrome, occasionally revisional surgery was
      performed.

PMID- 9289270
TI  - [Delayed rupture of the spleen in a multiply injured patient].
AB  - The authors present a case of delayed rupture of the spleen in a polytraumatised
      patient. This entity was defined as a late occurrence of signs and symptoms
      attributed to splenic injury not detected by diagnostic computed tomographic
      scanning during the initial examination. The mechanisms in which the delayed
      rupture of the spleen occurs are discussed and the conclusion is that the delayed
      rupture of the spleen represent a real clinical entity.

PMID- 9289269
TI  - [The experimental heterotopic transplantation of an isolated segment of colon].
AB  - The heterotopic transplantation of isolated colon segment was achieved in the
      cervical region, for to study the behaviour of the colon in this new situation.
      The study included 20 dogs from which there were taken segments of 10 cm length
      from, the left colon. Then was prepared the common carotid artery, superficial
      jugular vein and their branches. In 5 dogs the cervical esophagus was resected.
      Then was performed the transplant using micro-surgical techniques. In 15 dogs the
      colon was exteriorized at the skin and in 5 dogs the colon was placed between the
      ends of the esophagus. In 76% of cases the postoperative evolution was good. From
      the viable colon transplants were taken fragments for histologic examinations
      after 1, 2 respectively 4 weeks postoperative. The results obtained, recommend
      the colic transplant as a possible graft for repairing the cervical esophagus
      defects.

PMID- 9289271
TI  - [Vaccination against typhoid fever: results and perspectives].
AB  - The review deals with the world history and the current status of typhoid fever
      vaccination. It analyzes parenteral and oral killed cellular, oral live
      attenuated, molecular vaccines are analyzed. The results of field trials of
      parenteral and oral vaccines in the areas showing different epidemiology and
      incidence are analyzed. The problems in the designing of molecular typhi vaccines
      are considered. The results of designing the new generation vaccines S. typhi
      strains attenuated by means of site-specific mutagenesis and Vi-polysaccharide
      protein conjugates are presented.

PMID- 9289272
TI  - [Molecular mechanisms underlying bacillus anthracis infection at early stages and
      search for novel vaccines].
AB  - The developmental mechanisms of anthrax immunity were studied. Immunization was
      found to generally generate specific antibodies and lysozyme. Collectively, all
      the factors are responsible for suppressing the development of spores in the
      body. This proves the fact that the immunity is directed not only towards the
      exotoxin of B. anthracis, but it affects mainly the formation of vegetative
      cells. On entering the immuned body, vegetative cells may cause B. anthracis
      infection because antitoxic antibodies have no effect on encapsulated cells. The
      findings indicate that any anti-anthrax vaccine strain must show a complete
      immunological response in the body, as well as constitute immunity to all
      pathogenetic factors of B anthracis.

PMID- 9289274
TI  - [Morphology, ultrastructure and populational features of bacteria francisella].
AB  - The morphology, ultrastructure of cells and the structure of microbial
      populations of various bacteria of the Francisella genus were estimated by
      electron microscopy. The strain 503 has been found to produce a bacterial
      population that is most homogeneous in shape and size. It contains microbes of
      only round and avoid forms, 0.5-0.6 micron in size. In addition of oval and round
      microbes there are ellipsoid and rod-shaped ones in the strains 15/3M, A. Cole
      120, 117, etc. The largest tularemia microbes are typical of the strain Schu. The
      bacteria of all strains are covered by a capsule-like coat with well-defined
      borders. A thick capsule (0.12-0.35 micron) is specific for virulent strains
      whereas a thin capsular coat (0.06-0.12 micron) is encountered in vaccinal and
      avirulent microbes. The cells of the strain 503 were also shown to have the
      thickest envelope. All tularemia microbes have an asymmetric structure in the
      outer and cytoplasmic membranes due to the location of the bulk of intramembrane
      particles on their inner hydrophobic surfaces. Some F. tularensis microbes are
      able to produce keel-like protrusions on the outer membrane. The microbial
      nucleotide occupies 55-65% of the cytoplasmic volume and forms about 20-30 DNA
      membrane contacts. Under unfavourable conditions, the microbes are capable of
      producing cell envelop protrusions and involutional cells, 0.1-0.3 micron in
      size.

PMID- 9289275
TI  - [Prion infections: most important medical and veterinary aspects].
AB  - The paper reviews the most important and topical information on prionic diseases
      in the medical and veterinary context. It gives data on bovine sponge-like
      encephalopathy and other new prionic infections in animals, as well as on a new
      type of the Greutzfeldt-jakob disease. The common pathology, pathogenesis, and
      transmission of the infections of this group, a prionic concept of their
      etiology, constituents of present-day epidemiological survey are generalized.
      Some most tasks of medical and veterinary importance, which are most essential to
      Russian science, are worded in the conclusion.

PMID- 9289273
TI  - [Elucidation of functionally active domains in molecules of protective antigen
      bacillus anthracis's toxin].
AB  - Limited proteolysis has established that the protective antigen (PA) molecule
      consists of four functional-active domains. So, the shielding domain borrows an
      area in the linear structure of the PA molecule with NH2 of the end up to Lys 166
      and plays a conducting role in the proteolytic activation of PA. The associative
      domain, engaging in the area Arg 167-Met266, plays a key role in the interaction
      with LF or EF at self-assembly toxic complexes LT or ET. The stabilizing domain
      borrows in the linear structure of the PA molecule are with Gly351 up to Met434.
      On the one hand, this area promotes formation with LF conformationally steady
      toxic complex's, and, on the other, takes a direct participation in the formation
      of a hydrophobic channel by which the molecule LF or EF enters the target cell.
      The receptor domain, representing a COOH-terminal area, starting from Leu663
      amino acid, begins to interact with specific receptors on the macrophages and
      thus delivers the toxic complex to the target cell. It has been found that in the
      molecule of lethal factor there are 3 functionally active domains located in the
      linear structure of the molecule as follows: the associative domain borrows an
      area from Lys39 up to Met242, stabilizing and effector domains occupy areas from
      Leu517 to Lys614 and from that point to Lys COOH-terminal amino acid.

PMID- 9289276
TI  - [Tularemia vaccine strain is a potential vector].
AB  - The immunological and genetic properties of Francisella tularensis vaccine strain
      are discussion with regard to its use to produce recombinant vaccines. This
      bacterium-based vector is supposed to be an excellent object for investigating
      the role of protective antigens in the development of immunity against
      intracellular bacteria.

PMID- 9289279
TI  - [Designing the latex test system for express identification of legionella in the
      external medium and clinical materials].
AB  - A highly sensitive latex test system for identification of Legionella in the
      external medium and clinical materials have been designed. Protein antigens and
      polysaccharide components of the outer membrane of the agent were analyzed.
      Proteins having a molecular mass of 45, 29, and 24 kDa, as well as a
      polysaccharide component of LPS were found to be common for all L. pneumophila
      species. Highly affinic immunoglobulins to the antigenic components obtained were
      covalently linked with latex particles. The test system developed does not give
      cross-reactions with other microorganisms. The sensitivity of the system is 10(4)
      COE/ml. Testing water and clinical material samples confirmed that the developed
      system is more sensitive than the bacteriological method and the direct
      fluorescence test. In addition, the system is simple to use, cost-effective, it
      requires little time (no more than 5 min).

PMID- 9289277
TI  - [Immunogenic potential of glanders and melioidosis agents].
AB  - Unlike the glanders agent, the superficial structures of the melioidosis agent
      were demonstrated to be responsible for marked was immunosuppressive activity.
      Some antigenic fractions suppressing the blast transformation of lymphocytes,
      reducing the count of T helpers and profoundly potentiating the infection in vivo
      were isolated from P. pseudomallei cells. The immunogenic and immunosuppressive
      activities of both agents' superficial structures were studied by high
      performance chromatography. Antigenic complexes that were able to protect
      immunized laboratory animals against fatal infections and to prevent bacterial
      carriage due to the activation of T cells and to the bacterial activity of
      macrophages were identified. A composition comprising several immunogens was
      found to provide an additive protective action against both causative agents.
      Therefore, the composition may be considered to be a prototype of a molecular
      antipseudomonadic vaccine.

PMID- 9289280
TI  - [Recombinant plasmids carrying yersinia pestis fra-operon: specific features of
      genetic transmission, inheritance and expression in attenuated enterobacterial
      cells].
AB  - The study was undertaken to study the specific features of transformation of E.
      coli strains having different R-chemotypes, Y. pestis, S. minnesota R595, and S.
      typhi Ty21a by plasmids carrying Yersinia pestis Fra-operon which controls the
      formation of a plague microbe capsular F1 antigen in this microorganism. Calcium
      transformation was shown to be rather effective for the plasmids constructed on
      the basis of a cosmid vector (pFS1), rather than those designed by using the Y.
      pestis plasmid pPst I (pFSK3, pP3). The level of plasmid stability varied and
      failed to correlate with taxonomy fitting and the chemotype of a recipient
      strain. The cells of all recombinant strains produced F1 antigen, secreted it
      into the environment; the synthesis was temperature-regulated. F1 was identified
      both in the diffuse precipitation and serological tests. The levels of F1 antigen
      synthesis decreased whereas nutritious requirements for the maintenance of
      protein synthesis increased for bacterial strains with higher levels of LPS
      reduction.

PMID- 9289278
TI  - [Effect of TRA-system of plasmids RP4 and R68.45 on pseudomonas mallei
      virulence].
AB  - In Pseudomonas mallei, spontaneous mutants (Tra- mutants) of the plasmids RP4 and
      R68.45, losing the ability to transfer at conjugation are formed. The plasmids
      RP4 and R68.45 with Tra(+)-phenotype caused a decrease in P. mallei virulence for
      laboratory animals. At the same time, Tra- mutants of these plasmids do not
      affect P. mallei virulence. The insertion of DNA fragment of about 1900 bp into
      the plasmid transfer gene regions (tra-2-tra-3) gave rise to RP4 and R68.45 tra
      mutations detectable on examination.

PMID- 9289281
TI  - [Stable expression of heterologous proteins in salmonella: problems and
      approaches to their designing].
AB  - Live attenuated Salmonella vaccines may be used as carriers of heterologous
      antigens. The optimum expression system for each heterologous antigen requires to
      be established on an individual basis. This will ensure that the antigen in
      question is produced at appropriate levels and in the correctly folded
      conformation. Different techniques for producing stable recombinant Salmonella
      strains suitable for their use as bivalent vaccines.

PMID- 9289282
TI  - [Targeted action proteins as potential drugs].
AB  - The data available in the literature over the past decade as to the design and
      use of directly acting proteins in the treatment of a number of diseases are
      analyzed. The structure and functions of toxins inhibiting protein synthesis are
      reviewed. The structural and functional properties of conjugated and recombinant
      immunotoxins are compared and clinical findings are reviewed. Particular emphasis
      is laid on the requirements for such hybrid proteins. It is concluded that
      specific cell elimination as a principal approach to treating tumors, autoimmune
      and other diseases will find wide medical application just in the near future.

PMID- 9289284
TI  - [Position effect mosaicism in polytene chromosomes of pseudonurse cells of the
      otu(11) Drosophila melanogaster mutant].

PMID- 9289283
TI  - [A new member of the MER2 repeat family is detected in the promoter region of the
      human X11 gene].

PMID- 9289285
TI  - [Dioxin and furan levels in Baikal seals].

PMID- 9289286
TI  - [Acquisition of ability to metastasize by spontaneous tumors under the effect of
      metastazin 1 in transgenic animals].

PMID- 9289287
TI  - [Disruption of phospholipid metabolism and intensity of free radical oxidation of
      lipids in rat splenic lymphocyte membranes exposed to the mycotoxin zearalenone
      and the role of sodium thiosulfate in their leveling and correction].

PMID- 9289288
TI  - [Distribution of DNA-synthesizing cells in migrating colonies of human epidermal
      keratinocytes].

PMID- 9289290
TI  - [Discovery of plantar glandular organs in the marbled polecat Vormela peregusna
      (Mustelidae, Mammalia)].

PMID- 9289289
TI  - [Viability of smallpox virus in scabs from patients].

PMID- 9289291
TI  - [Circadian variation of lung function in bronchial asthma].

PMID- 9289292
TI  - [The usefulness of certain diagnostic tests for diagnosis of bronchial asthma in
      epidemiologic investigations].
AB  - The study was carried out to assess accuracy of questionnaire, bronchial
      inhalation challenge, physical examination and spirography in identifying
      subjects with bronchial asthma of 582 chemical industry workers, compared with 80
      persons with atopic bronchial asthma in epidemiologic screening study. It was
      found, that based on standards against which tests have been verified, none of
      them have shown 100% sensitivity and specificity in recognition of asthma in
      screening group. The best accurate tests in recognition of asthma were bronchial
      inhalation challenge (sensitivity 47%, specificity 96%) and questionnaire
      (sensitivity 68%, specificity 88%). Bronchial hyperreactivity showed the highest
      positive predictive value (82%) in prevision cases of the disease. In
      conclusions, standard mostly close to bronchial asthma in epidemiologic surveys
      should contain bronchial hyperreactivity and typical asthmatic symptoms according
      to the questionnaire.

PMID- 9289293
TI  - [Genetic factors and environmental factors regulating synthesis of immunoglobulin
      E].

PMID- 9289294
TI  - [The role of neuroendocrine cells and bombesin neuropeptides in the pathogenesis
      of smoking related diseases, especially chronic obstructive pulmonary disease].

PMID- 9289296
TI  - [A report from the IV Inter-European Conference on the subject of lung neoplasms
      in Gdansk, 26-29 September 1996].

PMID- 9289295
TI  - [Resolution of the main board of the Polish Society of Allergology].

PMID- 9289297
TI  - [History of the thoracic surgery ward at the WZP ZOZ Lung Diseases and
      Tuberculosis Sanitarium in Otwock].

PMID- 9289299
TI  - [Experimental model of chronic bronchitis].
AB  - In 20 rats bronchitis was evoked by permanent 12-week long inhalation of SO2. For
      this purpose a special chamber with gas supply was prepared. In all rats exposed
      to SO2 changes in cellularity of BALF were found (a statistically significant
      increase of the percent of macrophages and neutrophils). Histologic examination
      revealed bronchial changes especially in epithelium. The method applied, based on
      an original technology is cheap and effective and can be recommended in
      developing experimental bronchitis.

PMID- 9289298
TI  - [The influence of multiple histamine inhalation on nonspecific airway
      hyperresponsiveness to histamine in patients with bronchial asthma].
AB  - The study was performed in 19 patients with stable mild/moderate asthma aged from
      16 to 66. Nonspecific airway hyperresponsiveness (AH) to histamine was measured
      according to Cockcroft's et al. method and expresses as PC20H in mg/ml. The study
      was controlled by inhalation of PBS. The histamine or PBS challenges were
      performed three times at 45 min. intervals on the third day in case when the
      stability of AH on two preceding days was observed. The geometric means of PC20H
      (xg PC20H) during the consecutive three days did not change. They were 0.97,
      0.92, 0.87 mg/ml (p > 0.05) respectively. Three times histamine challenges
      performed on the same day induced the decrease of AH (xg PC20H increased from
      1.48 to 6.55 mg/ml) in 5 patients. In 4 other subjects the increase of AH was
      observed (xg PC20H decreased from 1.14 to 0.20 mg/ml). In 10 subjects the three
      times histamine challenges performed on the same day had no influence on AH to
      histamine.

PMID- 9289301
TI  - [An increase of nonspecific airway hyperreactivity after repeated challenge with
      subthreshold doses of allergen in asthma patients].
AB  - The study was performed in 11 patients suffering from stable mild and moderate
      atopic asthma. Bronchial allergen challenges were performed according to Chai et
      al method. Airway hyperreactivity-AH (PC20H in mg/ml) was determined in each
      study day before subthreshold allergen inhalation dose, meaning the dose which
      did not induce asthmatic responses. Then FEV1 was measured in 2, 5, 15, 30 i 60
      min. after allergen provocation throughout 4 to 9 consecutive days. A significant
      increase of PC20H was observed in 8 patients (xg PC20H in whole group decreased
      from 0.93 to 0.35 mg/ml after allergen challenges). The authors conclude that
      allergen inhalation challenge without asthmatic bronchial responses can cause an
      increase AH.

PMID- 9289300
TI  - [The influence of heparin on the course of bronchitis experimentally provoked by
      sulfur dioxide in rats in evaluation of lung histology and cytology of bronchial
      alveolar lavage fluid].
AB  - The aim of our study was to evaluate the influence of heparin on inflammed
      bronchial mucosa in rats. Sixty five animals were used in the study; 5 of them
      constituted the control group, whereas 60 were submitted to long term SO2
      irritation in specially constructed chamber, what resulted in chronic bronchitis.
      Low molecular weight heparin preparation--Frexiparine has been administered in
      inhalation or parenterally to 40 rats, simultaneously or immediately after SO2
      exposition. In all animals exposed to SO2 the BALF evaluation revealed
      predomination of inflammatory cells. The results obtained in healthy rats were
      different and BALF cellular sediment contained 92% of epithelial cells. However
      in animals submitted to SO2 irritation and simultaneous heparin treatment we
      observed significant increase of the number of inflammatory cells in BALF in
      comparison to healthy rats but it was not as high when compared to animals
      irritated only with SO2. In all animals exposed only to SO2 we were able to find
      disseminate inflammatory changes and/or planoepithelial metaplasia in bronchial
      specimens. However we did not observe any sings of inflammation in specimens
      obtained from 50% of heparin treated rats, whereas in the other 50% they were
      described as mild or moderate. CONCLUSIONS: 1. Low molecular weight heparin
      decreased signs of experimentally provoked bronchial inflammation in rats. 2.
      Simultaneous heparin and SO2 administration was extremely efficient. This finding
      suggests prophylactic properties of heparin. 3. The heparin activity does not
      depend on inhalatory or parenteral way of administration.

PMID- 9289302
TI  - [Surgical lung volume reduction in emphysema].

PMID- 9289304
TI  - [Frequency of positive skin tests in asthma patients over 30 years].
AB  - Frequency of positive skin in adults with asthma is poorly understood. 153
      persons aged over 30 years were selected out of 575 patients suspected of asthma
      (26.6%). Positive skin reactions among adults, were confirmed in 64.1% of the
      examined patients. Positive skin reactions were analysed according to age and
      sex. Opinion about low frequency of allergy and asthma in elderly should be
      verified.

PMID- 9289303
TI  - [Evaluation of hyperresponsiveness to the exercise challenge test in school
      children].
AB  - Bronchial hyperresponsiveness (BHR) to the exercise challenge test was measured
      in 161 pupils randomly chosen from the epidemiologic survey of 2967
      schoolchildren (13 to 14 yr of age). In the study group there were 73 pupils who
      were identified as "ever wheezers" by the ISAAC questionnaires, and 88 ones as
      the control group. BHR was measured as the percentage drops in FEV, FEF50, FEF25
      75 from the baseline (% delta FEV1, % delta FEV50%, % delta FEF25-75%). The %
      delta FEV1 was significantly higher in the "ever wheezers" comparing to the
      control group, and this parameter was also significantly higher for the "wheezers
      in the last 12 mo" in comparison to "ever wheezers", who had no symptoms in the
      last year. The "ever wheezers" group had higher % delta FEF50%, % delta FEF25-75%
      but the value was not significant when compared to the control group. In the
      epidemiologic survey, the sensitivity and specificity for the exercise challenge
      test as a screening test (level %FEV1 > 11%) to identify "wheezers in the last
      12mo" were 39% and 81%, respectively, and to identify the "diagnosed asthma"
      group were 40% and 76%. The BHR was modified by atopy (measured with the allergic
      skin tests) and the diagnosis of asthma.

PMID- 9289306
TI  - [Intralobar pulmonary sequestration treated surgically in a patient with
      sarcoidosis].
AB  - Pulmonary sequestration is an uncommon but clinically significant congenital
      malformation characterised by the presence of nonfunctioning lung tissue that
      receives its blood supply from anomalous systemic arteries and has no
      communication with the normal bronchial tree. We describe a patient with an
      intralobar pulmonary sequestration of the left lower lobe associated with
      sarcoidosis. The patient was treated successfully by resection of the lesion. The
      postoperative period was uneventful. We found no report where a pulmonary
      sequestration was associated with sarcoidosis.

PMID- 9289305
TI  - [Evaluation of the efficacy of immunotherapy with allergovit and catalet in
      patients with hay fever--multidrug evaluations].
AB  - The aim of this study was to compare the efficacy of the immunotherapy by
      Allergovit and Catalet. 699 patient in age 5-56 were desensitized. 213 were given
      Allergovit: 137 in one season, 56 in two seasons and 20 in three seasons and 484
      were given Catalet: 288 in one season, 151 in two seasons and 45 in three
      seasons. The Catalet vaccine contains 12 grasses, rye and plantain pollen, but
      Allergovit contains a group of grass pollen-60% and rye pollen-40%. Qualification
      to the desensensitization was performed on the ground of clinics symptoms,
      positive (+ + + +) prick skin tests, of specific antibody IgE, positive
      provocation nose test presence and symptoms connected with pollen fall checked
      every day in the area of Poznan, Lodz and Katowice city. Estimation of the
      immunotherapy efficiency was assessed by patients, who noted their remarks in
      prepared "Patient card" using enclose score. In result of desensitization by
      Allergovit we achieved good and very good improvement (0 + 1 score) after one
      desensitization season in 77.3% patients, after two seasons in 85.7% and after
      three seasons in 90.0%, on the contrary by patients desensibilized by Catalet
      results good and very good were achieved in 50% after one season, after two
      seasons in 63.6% and after three seasons in 77.8%. CONCLUSIONS: Better results
      were achieved in patients desensibilized by Allergovit than Catalet. It is
      necessary of compose the contain of Catalet vaccine for every patient.

PMID- 9289307
TI  - [Pulmonary alveolar proteinosis--diagnostic problem].
AB  - A case of a 37 years old woman with suspicion of sarcoidosis is presented.
      However, the course of disease was not typical for sarcoidosis. The previous
      diagnosis was verified. The results of bronchoalveolar lavage and histological
      examination of lung biopsy sample revealed features characteristic for pulmonary
      alveolar proteinosis. The diagnostic methods, clinical course of disease and the
      ways of treatment are presented.

PMID- 9289308
TI  - [A case of sarcoidosis with massive pleural and pericardial effusion].
AB  - A rare case of sarcoidosis with massive pleural and pericardial effusion in 30
      year-old female patient was presented. Diagnosis was established on the basis of
      the specimen examination of bronchial mucosa and lymph nodes. Suspicion of heart
      sarcoidosis was supported by radioisotopic examination. Following steroid
      therapy, fast disappearance of the pathological changes was observed.

PMID- 9289309
TI  - [Pneumococcal pneumonia with a sever course].
AB  - The authors present a case of a 70-years old patients with bilateral pneumonia of
      pneumococcal etiology. During the treatment, after the initial improvement
      respiratory failure was observed and mechanical ventilations was applied.
      Following this procedure appeared such complications as left pneumothorax and
      pleural empyema. After drainage and evacuation of purulent fluid from pleural
      cavity the clinical improvement was observed. The case shows how pneumonia is
      still dangerous, especially for patients with chronic obstructive pulmonary
      disease.

PMID- 9289310
TI  - [Coexistence of Pneumocystis carini infection and pertussis].

PMID- 9289311
TI  - [Circadian variation of lung function in health persons].

PMID- 9289312
TI  - Diagnostic imaging in oncology. Proceedings of a meeting. Naples, Italy, 28-30
      April 1993.

PMID- 9289313
TI  - Thymectomy and autoimmunity.

PMID- 9289314
TI  - [Comparative rhinomanometric measurements in children with cleft palate after
      cleft closure with and without velopharyngoplasty].
AB  - To answer the question if a cranially based pharyngeal flap in patients with
      cleft palate could affect nasal breathing, 49 children were examined by active
      anterior rhinomanometry with and without decongestion of the nasal mucosa. All
      patients were between 10 and 12 years old. In 18 of them palatoplasty with a
      cranially based pharyngeal flap was performed at the average age of 3.5 years.
      The control group consisted of 21 children who had been treated with an
      intravelar veloplasty without any flap at the age of 11-13 months. None of the
      patients had any appreciable narrowing of the nasal airways. Using the U test we
      found no significant difference between the inspiratory breathing volume of both
      groups. The difference between in- and expiratory volume in each group showed no
      significance either while the volumes we examined before and after decongestion
      differed significantly. Thus, we cannot conclude that the cranially based flap
      affects nasal breathing in cleft palate patients compared to those without any
      flap.

PMID- 9289316
TI  - Material selection for foot orthoses.

PMID- 9289315
TI  - The menopausal transition: a different view. Proceedings of an international
      symposium. Leiden, The Netherlands, 18-19 June 1997.

PMID- 9289317
TI  - Firing turns on religious jewelry.

PMID- 9289318
TI  - [Science and society: determinants of a compromise].

PMID- 9289319
TI  - [Lung volume reduction surgery in patients with emphysema].

PMID- 9289320
TI  - [Outpatient emergency care in pneumology. A method to alleviate pressure of
      hospital emergency services].
AB  - We analyze the result of using a pneumological rapid-attention facility for
      diagnosis and immediate treatment of patients with respiratory symptoms arriving
      at the emergency room of University Hospital Virgen del Rocio in Seville (Spain).
      In the first six months the outpatient service saw 321 patients (male/female
      ratio 2.6), most of whom were between 55 and 75 years of age and had never before
      seen a pneumologist (83.4%). Dyspnea was the most common respiratory symptom
      named (by 35% of patients), and acute exacerbation of chronic obstructive
      pulmonary disease was the most usual diagnosis (in 19.1%). Only 21 (7%) were
      admitted to the hospital. We that creating the outpatient unit effectively met a
      societal need for rapid diagnosis and treatment of patients with respiratory
      complaints in the area served by our hospital emergency service.

PMID- 9289321
TI  - [Relation between asthma and atopy markers in children and young adults].
AB  - The aim of this study was to assess whether atopy, measured as total IgE level
      (IgEt) and/or skin test (ST) reactivity is related to bronchial asthma in the
      same way in children and young adults. Three hundred fifty-three children between
      11 and 15 years of age (mean 12.6 years) and 208 adults between 20 and 44 years
      old (mean 32.1 years) were selected randomly as representative of persons living
      in the city of Huelva (Spain). All subjects filled out a questionnaire on
      respiratory symptoms (The European Community Respiratory Health Survey--[ECRHS])
      and were given a methacholine challenge test (MT) with results expressed as PD20
      as well as IgEt and ST assessments of atopy. We defined bronchial asthma as the
      association of having experienced wheezing within the last 12 months and having a
      positive ST. Among children, 4.5% suffered bronchial asthma. Among adults the
      proportion was 5.3%. The IgEt value that best discriminated between asthmatics
      and non asthmatics was 145.5 U/ml in children (sensitivity 75% and specificity
      69.1%) and 96.6 U/ml in adults (sensitivity 90.9% and specificity 73.6%). A
      logarithmic transformation (log IgEt) was used to study the relation between
      bronchial asthma and IgEt. By simple analysis, IgEt and ST were related to
      bronchial asthma in children (p = 0.002 and p < 0.0001, respectively), while only
      IgEt (p < 0.001) was related in adults. By multiple regression analysis,
      controlling for both factors simultaneously as well as for smoking in adults, we
      found that ST (p = 0.023) but not IgEt was related in children, whereas IgEt (p =
      0.0005) but not ST was related in adults. We conclude that the two markers of
      atopy studied are related to bronchial asthma differently and have different
      manifestations at different stages of life. ST is more useful in children,
      whereas IgE determination is of more use in adults.

PMID- 9289322
TI  - [High-dose endobronchial brachytherapy in malignant tumors of the lung].
AB  - To assess clinical and bronchoscopic evolution as well as outcome in patients
      treated with high dose rate (HDR) endobronchial brachytherapy in order to
      determine its effectiveness for treating malignant airway obstruction. From May
      1993 to January 1996, 10 patients (9 men and 1 woman) with bronchogenic carcinoma
      received 24 HDR endobronchial treatments. The mean age was 61.9 years (range 34
      to 78 years). Inclusion criteria were, for palliative treatment, incurable
      endobronchial cancer, and, for curative treatment, residual tumor in the margins
      after resection, or endobronchial tumor that could not be treated surgically.
      Exclusion criteria were site of lesion unsuitable for placement of the
      brachytherapy catheter, life expectancy less than two months, Karnofsky index
      less than 60 or absence of signed consent from the patient. Response criteria was
      either complete or partial for symptoms and endobronchial tumor. Ten patients
      received 24 HDR endobronchial treatment from and HDR source of I192 radiation
      with remote afterloading. A flexible bronchoscope was passed down the bronchial
      tree toward the area affected by the tumor. At intervals of one week, four
      separate fractions between 5 and 10 Gy were delivered to a depth of 0.5 to 1 cm
      and a length of 1 to 5 cm. One month after the last session, each patient
      underwent endoscopic examination with removal of a histology specimen. Response
      was considered complete based on clinical signs in 66%; response was complete
      based on endoscopy in 50%. Three patients died within the first year after
      treatment and one patient did not return for a follow-up examination. Five
      patients who had been followed for less than one year were still living. The
      remaining patient was living 18 months after treatment. All tolerated the
      treatments well, showing neither early nor late complications. HDR endobronchial
      brachytherapy is effective both for preventing and relieving malignant
      endobronchial obstruction. Response to therapy is good, as shown by clinical
      symptoms and endobronchial examination. HDR endobronchial brachytherapy can cure
      in carefully selected patients.

PMID- 9289323
TI  - [Surgical diagnostic procedures in superior vena cava syndrome].
AB  - We evaluate surgical risk and efficacy in a series of 29 patients referred to us
      over a 22-year period with diagnoses of superior vena cava syndrome (SVCS)
      requiring surgical removal of histology specimens. We did 34 procedures: 23
      mediastinoscopies, 6 mediastinotomies, 2 thoracotomies, 2 sternotomies and 1
      Daniel's biopsy procedure. Mean surgical time was 88 minutes. There were no
      serious surgical complications and no deaths. Histological diagnoses (27
      malignant and 2 benign) were obtained for all patients. The efficacy of
      mediastinoscopy was 82.6% whereas the efficacy of mediastinotomy was 66.6%. We
      believe that diagnostic surgical procedures in patients with SVCS are safe and
      effective. The use of blind radiation therapy is unjustified, given that some
      patients present benign processes or malignant ones that are more responsive to
      chemotherapy. Moreover, subsequent histologic confirmation can be made more
      difficult after blind radiation.

PMID- 9289324
TI  - [Application of clinical guidelines in the management of pleural effusion].
AB  - To analyze compliance with recommendations on the diagnosis and treatment of
      pleural effusion (PE), we conducted a retrospective study of 60 consecutive
      patients with PE. Thirty had been treated on the internal medicine ward (IM) and
      30 had been cared for in the pneumology unit (P). Twelve variables were studied:
      3 reflected the efficacy of medical intervention and 9 were related to diagnostic
      and therapeutic procedures as recommended by the American Thoracic Society and
      the American College of Physicians. PE was generally managed in accordance with
      the aforementioned guidelines. However, a number of unnecessary analytical tests
      were performed on pleural liquid from the first thoracocentesis. Although IM
      patients were comparable to P ward patients as to age, sex and concurrent chronic
      disease, the mean hospital stay was shorter for P ward patients (16 days versus
      18 days in the IM ward, p < 0.05), and the percentage for whom an etiological
      diagnosis had been achieved upon discharge was higher in the P group (56% of P
      patients versus 26% of IM patients, p < 0.002). More P group patients than IM
      patients were followed up after discharge (83% versus 40%, respectively; p <
      0.001). There were no significant differences in the remaining variables. Within
      the limitations of any retrospective study, these results allow us to conclude
      that PE is generally managed in accordance with international guidelines at our
      hospital and that diagnostic efficacy is greater on the pneumology ward, where
      mean stay is shorter.

PMID- 9289325
TI  - [The IBERPOC project: an epidemiological study of COPD in Spain. Scientific
      Committee of the IBERPOC study].
AB  - The aim of the IBERPOC study is to determine the prevalence of chronic
      obstructive pulmonary disease in Spain, to collect data on its management, the
      degree of variability in diagnosis, treatment and quality of life, and to
      estimate the mean annual direct health costs for these patients. IBERPOC is a
      multicentric transversal epidemiologic study that selects participants from
      populations corresponding to geographic and/or administrative areas using a
      probabilistic formula. Included are both males and females between 40 and 69
      years of age who are residents in the study area and living outside institutions.
      This article describes the study design, sample selection criteria, the method
      and its application, and control systems used to prevent errors in patient
      selection and in pulmonary function testing. The schedule for data analysis is
      also included.

PMID- 9289326
TI  - [Estimation of initial interobserver variability of forced spirometry in the
      multicenter epidemiological study IBERPOC. Scientific Committee of the IBERPOC
      study].
AB  - To estimate the interobserver variability and degree of agreement for basic
      spirometric parameters before beginning field work for the IBERPOC Project. Study
      of agreement between 7 observers (pneumologists) and a gold standard, using a
      scheme of incomplete balanced and randomized blocks with an equal number of
      spirometric measurements (n = 3) per patient and an equal number of measurements
      (n = 9) per observer performed at the same session. The study population
      consisted of 14 patients with different degrees of air flow obstruction and 7
      normal volunteers. Statistically significant differences attributable to subjects
      (inter-patient variability) were found for the three variables analyzed.
      Variability attributable to the observer was found for FVC and FEV1 but not for
      FEV1/FVC. The greatest interobserver differences were found for FEV1, such that 4
      of the 7 observers recorded values that were significantly different from the
      mean (p < 0.05). The differences were less marked for FVC and for the FEV1/FVC
      ratio, with only 2 observers recording significantly different values for each
      variable. The high degree of reproducibility as well as the excellent
      interobserver agreement found in this standardization session provide an a priori
      guarantee of validity for spirometric measurements and rule out the existence of
      differential bias in data recorded at the various geographic areas involved in
      the study.

PMID- 9289327
TI  - [Acute eosinophilic pneumonia in a pregnant woman].
AB  - Acute eosinophilic pneumonia is a recently described pulmonary phenomenon
      involving rapidly progressing respiratory insufficiency. Although it can appear
      at any age, it has never been reported during pregnancy and its impact on
      gestation is therefore unknown. We describe the clinical signs and course of
      disease in this first report of acute eosinophilic pneumonia in a pregnant woman.
      We emphasize the diagnostic utility of bronchoalveolar lavage, the resolution of
      symptoms without corticoid treatment and, mainly, the absence of adverse
      repercussions of the disease on pregnancy.

PMID- 9289328
TI  - [Pneumonitis caused by mesalazine].
AB  - 5-aminosalicylic acid (5-ASA) has been used to treat inflammatory bowel disease
      satisfactorily. Lung disease related to 5-ASA administration has been described
      only rarely. We report a case of alveolitis related to 5-ASA treatment in a woman
      with Crohn's disease. We review the literature and describe clinical, biological
      and radiological manifestations, along with the clinical course of this
      complication.

PMID- 9289329
TI  - [Trousseau's syndrome in lung adenocarcinoma. The rare appearance of venous
      gangrene].
AB  - Trousseau's syndrome includes a wide range of coagulation disorders, migratory
      thrombotic phenomena being the main associated entities. Treatment is difficult
      and venous gangrene constitutes a rare but deadly final stage that is
      particularly painful for the patient. The outlook after treatment is poor.

PMID- 9289330
TI  - [Pleural metastasis of choroid melanoma].

PMID- 9289331
TI  - [Tracheotomy complicates disease in patients with mediastinitis of oropharyngeal
      origin].

PMID- 9289332
TI  - [Medical and medico-social aspects of the birth rate and mortality under current
      conditions].

PMID- 9289334
TI  - [Various aspects of price formation in public health].
AB  - The main problems involved in estimating the cost of medical service are
      discussed. Up to the present time, there was no universal approaches to price
      formation in practical public health. Economists and public health organizers are
      not trained to cope with this task. Based on the results of five-year studies and
      published data, the author present in detail the methodology of practical price
      formation and offer the typical problems in price estimation. The recommendations
      contained in this paper will help improve the work of specialists in price
      formation and aid all those engaged in the sphere of paid medical service.

PMID- 9289335
TI  - [Strategy and methodology of professional preparation of personnel for work under
      conditions of carrying out market reform].

PMID- 9289336
TI  - [Theoretical and organizational aspects of primary health care in Russia].

PMID- 9289333
TI  - [Suicide from the standpoint of social medicine].
AB  - Demographic, social, and medical analysis of more than 30,000 suicide cases in a
      large region of Russia (Krasnodar region) over 1969-1994 showed the prevalence of
      men, subjects aged over 60, divorced and widowed subjects, individuals living
      alone, subjects without permanent occupation, mental patients, chronic
      alcoholics, and invalids in this group. The principal factors determining the
      processes of formation of the totality of suicides have been determined and the
      most prevalent social and hygienic characteristics of a suicide described. Groups
      with the highest level of suicides have been identified: narcomaniacs, mental
      patients, chronic alcoholics, disabled subjects. The authors emphasize not so
      much the medical, but the social aspect of the problem. They offer the priority
      research trends and organization measures aimed at investigation of the suicide
      phenomena and prevention thereof.

PMID- 9289337
TI  - [Medical staff in Russia].

PMID- 9289338
TI  - [The low effectiveness of public health management].

PMID- 9289339
TI  - [Problems in organization and management of Russian public health in the XXI
      century: style, strategy, system].

PMID- 9289343
TI  - [Number of consultations in an outpatient clinic practice].
AB  - Presents the results of introducing a new system of registration of physicians'
      work and patients' diseases at a municipal outpatient clinic.

PMID- 9289342
TI  - [The problem of staff imbalance in public health and its consequences].

PMID- 9289344
TI  - [Organization of the national public health system in Finland].

PMID- 9289341
TI  - [The system of training future leaders in public health].
AB  - The authors analyze the present-day status of the system of training specialists
      in public health organization in Russia. Based on the experience gained in St.
      Petersburg, they demonstrate that full-time training combined with studies by
      correspondence is the most effective approach to preparing such specialists.

PMID- 9289340
TI  - [Medico-social policy as an integral part of the strategy of present-day public
      health development in Russia].
AB  - The authors discuss the new approaches to the solution of a complex of
      medicosocial problems which should not be disregarded when developing the
      strategy of public health development under conditions of reformation of the
      Russian economy. An integral system of medicosocial care of the population both
      at the federal and regional levels should be formed and the mechanisms and
      methods of its realization developed in order to pursue an effective medicosocial
      policy, which represents an integral element of the strategy of public health
      development, with due consideration for the social, economic, demographic,
      ecological, sociohygienic, and other factors. The authors believe that
      medicosocial policy should be characterized by clear-cut strategic direction as
      regards all public health services.

PMID- 9289345
TI  - [Anatomy instruction at the Medical Faculty of Moscow University in the XVIII
      century].

PMID- 9289346
TI  - [A society of amateurs in the history of medicine].

PMID- 9289347
TI  - [History of sanitary protection in the Far East].

PMID- 9289348
TI  - [Family and problems of young mothers].
AB  - Discusses the problems of adolescent pregnancy and maternity in young age.
      Presents the sociohygienic characteristics of young mothers and their parents.
      Shows that the problem of young maternity became typical for complete and
      seemingly successful families in the majority of cases. Pays special attention to
      difficulties (material, communal, psychological, etc.) experienced by adolescent
      girls becoming mothers before they are 18. Validates the necessity of developing
      and introducing addressed programs of medicosocial support of young mothers and
      adolescent families, which should be aimed at the soonest possible solution of
      acute vital problems (communal, psychological, economic, medical (including
      contraception), those associated with completion of education, etc.).

PMID- 9289350
TI  - GABA mechanisms in the cerebral cortex. Proceedings of a symposium. Montreal,
      Quebec, Canada, 9-10 May 1996.

PMID- 9289349
TI  - [An outline of a method for estimating the calculated economic cost of malaria
      cases: its application to a rural area in Burkina Faso (Western Africa)].
AB  - A precise method to estimate the cost of malaria in a rural area was developed
      and applied in 3 villages in Burkina Faso. The estimate takes into account direct
      costs such as consultation fees, microscopic examinations, medication and
      transport as well as indirect costs caused by lost work-days. The formula uses 6
      variables: age of subject, degree of invalidity, duration of illness, profession,
      income and percentage of income lost. In the region of Bobo-Dioulasso, 3065
      health centre clients were registered in the course of the study: 17% had been
      clinically diagnosed as having malaria but this was confirmed microscopically in
      only 11.6% of cases; 73.1% were children aged < 5 years, 13.9% children aged 6-15
      years, 12.2% adults aged 16-50 years and 0.8% adults aged > 50 years. Most
      patients worked in agriculture and trade. The average duration of illness was 4
      days, with each case incurring a cost of $11.7 comprised of $8 direct costs and
      $3.7 indirect costs.

PMID- 9289351
TI  - Recovery of coliform bacteria from rural groundwater supplies using reduced
      oxygen concentrations during incubation.
AB  - The effect of decreased oxygen concentration during incubation of M-Endo medium
      on detection of coliforms from rural groundwater supplies was examined.
      Incubation oxygen concentrations of 0?(anaerobic GasPak), 4, 8, and 21%
      (atmospheric) were examined. Our findings point to several advantages of using
      anaerobic incubation for the isolation of coliforms: (i) higher verification
      rates with concomitant decreases in occurrence of false-positive coliforms; (ii)
      overall reduction in growth of nonsheen colonies; and (iii) reduction in colony
      size for nonsheen organisms, thereby minimizing crowding effects and facilitating
      enumeration of coliform colonies. However, these advantages were not sufficient
      to permit increased recovery of total coliforms as compared with aerobic
      incubation. In addition, the increased frequency of detecting false-negative
      coliforms during anaerobic incubation is a disadvantage to this method. While
      detection of total coliforms was reduced under conditions of anaerobiosis,the
      detection of fecal coliforms and (or) E. coli was not impeded.

PMID- 9289353
TI  - Anonymous peer review?

PMID- 9289352
TI  - Pyridine degradation and heterocyclic nitrification by Bacillus coagulans.
AB  - A gram-positive, pyridine-degrading microorganism identified as Bacillus
      coagulans has been isolated from contaminated soil by enrichment culture
      technique. Pyridine was used as sole source of carbon, nitrogen, and energy.
      Bacillus coagulans has a unique potential to reduce nitrogen from aromatic ring
      to ammonia and subsequently heterotrophically to nitrite and nitrate. The maximum
      degradation of pyridine was 94.1% within 72 h at 30 degrees C with a 7.57-h
      doubling time. The study suggests possible existence of aromatic degradation and
      heterotrophic nitrification in Bacillus coagulans.

PMID- 9289354
TI  - An unnecessary death.

PMID- 9289355
TI  - Verdict of the coroner's jury.

PMID- 9289357
TI  - Verbal abuse of hospital staff.
AB  - Many researchers have investigated verbal abuse against nurses, but few or no
      investigators have studied nurses and physicians collectively. At our 650-bed
      community hospital, anecdotal reports of verbal abuse of nurses by physicians led
      our research team to investigate.

PMID- 9289356
TI  - Teens for healthy living.
AB  - Improving the health and quality of life of adolescents is a fundamental
      aspiration of community health nurses. But developing health promotion programs
      that are attractive to young people can be a major challenge. In a rural Nova
      Scotia school district, this challenge has been met by bringing the teens
      themselves into the design and implementation of the program.

PMID- 9289358
TI  - Learning with the community for staff development.
AB  - Staff development, or inservice education, has been a part of the nursing work
      environment for many decades. Recently, our public health unit in British
      Columbia introduced an innovative and exciting approach to staff development.
      This fresh approach involves community participation and health promotion, the
      principles of primary health care, as well as participatory research--today's
      vital influences on nursing and health care generally.

PMID- 9289360
TI  - On being a witness.

PMID- 9289359
TI  - [Exercises that should be prescribed for heart patients].
AB  - The goal of cardiac rehabilitation is to assist the patient in regaining, as
      close as possible, normal functioning. Participation in an exercise program is
      one way to achieve this objective. Exercise improves not only the physiologic
      state of the patient, but also produces many psychosocial benefits. However,
      exercise prescription is different for cardiac patients, according to the factors
      associated with the type of cardiac pathology and the surgical intervention. The
      goal of this article is to inform and guide the nurse in prescribing exercise for
      cardiac patients. A case study of a patient with cardiac pathologies such as
      angina, myocardial infarction, and congestive heart failure is presented. The
      nurse will learn how to prescribe the appropriate types of activities as well as
      the intensity, duration and frequency of the training sessions. The nurse will
      also be able to recommend appropriate physical activities for phase II of cardiac
      rehabilitation, a phase embracing the time from hospital discharge through the
      following three months. Finally, a list of activities and hobbies, with various
      energy costs, is presented.

PMID- 9289361
TI  - Drug administration made safer.

PMID- 9289362
TI  - Reforming primary care.

PMID- 9289363
TI  - [The atrioventricular node: the ultimate "black box"?].

PMID- 9289364
TI  - [Myocardial reperfusion injury: implications in clinical practice].

PMID- 9289365
TI  - [Myocardial revascularization in patients with ischemic cardiomyopathy and left
      ventricular dysfunction].
AB  - In this study we evaluated the outcome of coronary artery bypass grafting (CABG)
      in patients with coronary artery disease and left ventricular dysfunction. The
      aim of the study was to identify the risk factors for operative and medium-term
      mortality. We evaluated 117 consecutive patients (98 men, 19 women, aged 42 to 84
      years, mean 65 +/- 9) with ejection fraction (EF) < 40%, operated on from January
      1994 to December 1995. Patients who had previously undergone CABG, or who had
      other procedures associated with CABG, were excluded. Preoperatively, mean EF was
      32 +/- 5%; 65 patients (56%) had angina and 62 (53%) had congestive heart failure
      in NYHA functional class III and IV. Hospital mortality rate was 5% (i.e. 6
      deaths). At multivariate analysis significant risk factors were: NYHA functional
      class IV and moderate/ severe mitral regurgitation. All patients were evaluated
      at a mean follow-up time of 13 +/- 8 months (range 3 to 30); 9 deaths occurred, 7
      due to cardiac causes. Actuarial survival rate at 24 months was 85 +/- 4%;
      freedom from death due to cardiac causes was 87 +/- 4%. Significant risk factors
      for medium-term mortality at multivariate analysis were age, moderate/severe
      mitral regurgitation and marked impairment of regional myocardial contractile
      function, evaluated by the wall motion score index (> or = 2.25). At follow-up
      the majority of patients showed improved clinical conditions: mean EF was 40 +/-
      8%; 8 patients (8%) had angina and 12 (12%) were in NYHA functional class III and
      IV. Myocardial revascularization in patients with coronary artery disease and
      left ventricular dysfunction is characterized by low operative risk and good
      survival rate at 2 years, with improvement of both angina and congestive heart
      failure. The best results were obtained in those patients who preoperatively
      showed the best regional contractile function, even though the global EF was
      poor, and in those with signs of reversible left ventricular dysfunction, such as
      angina or documented myocardial viability.

PMID- 9289366
TI  - [Reintervention in mitral valve prostheses. Analysis of risk factors].
AB  - From 1980 to 1996, 111 patients (83 females, 28 males, mean age 51.47 +/- 15.73
      years, range 1-76) underwent mitral valve replacement. Seventy-five patients
      underwent replacement of a biological valve and 36 of a mechanical valve. Three
      patients underwent a third operation. Seventy prostheses were replaced because of
      a structural dysfunction. Other causes of valve failure were: 24 thrombosis (23
      mechanical and 1 biological), 10 endocarditis (7 mechanical, 3 biological) and 4
      leakages (3 mechanical and 1 biological). One patient who had recurrent
      anticoagulant-related haemorrhage underwent reoperation to replace his mechanical
      valve with a biological prosthesis. Two patients had their valve replaced because
      of mismatch between size of the valve and body surface area. Thirteen operations
      were performed on emergency and 29 on urgency. There were 22 in-hospital deaths
      with a hospital mortality of 19.82%. Fourteen deaths (63.63%) occurred in
      patients operated on emergency or urgency. All deceased patients were in NYHA
      functional class III or IV. Our data suggest that risk of reoperation on mitral
      prosthesis is highly influenced by the preoperative functional class. In spite of
      the fact that replacement of biological valves should be more elective than that
      of mechanical valves, we did not find any difference between the two groups of
      patients.

PMID- 9289368
TI  - [Italian clinical cardiology research at the international level. Statistical
      data from the period 1983-1993].
AB  - Recent studies show that, among advanced countries, the rank of cardiological
      research finds Italy last for number of scientific publications and for gross
      expenditure on research and development. To assess more thoroughly the
      characteristics of Italian clinical cardiological research we examined, over the
      period 1983-1993, all original articles published by five important international
      cardiology journals (Circulation, American Heart Journal, American Journal of
      Cardiology, Journal of the American College of Cardiology and European Heart
      Journal). During the mentioned period the Italian contribution (743 articles over
      a total of 16375, mean prevalence of 4.5%) has increased from 3% in 1983-1985 to
      5.8% in 1991-1993 (p < 0.0001). Taking into account that research often results
      from the joint-work of different centers, the 743 articles derived from 1056
      contributions from just over 120 centers. Of these contributions 57% were from
      universities, 23% from hospitals, 19% from research institutes, and 1% from
      private foundations. The cooperation with foreign countries has steadily
      increased, particularly with the USA (45%) and with the European nations (42%).
      Within the first three names, the contribution of female Authors has increased
      from 7% in 1983-1985 to 16% in 1991-1993 (p = 0.0001). The mean prevalence of
      female Authors as last name was 4% and did not change with time. As to geographic
      distribution, 57% of the scientific publications comes from the North, 28% from
      the Centre, and 15% from the South. After adjusting these data for population
      size, the percentages were respectively 40, 46, and 14%. An index of productivity
      (the ratio between the number of scientific contributions from universities and
      research institutes and their funding) was highest in the North. The Italian
      scientific contribution to international cardiological research is not
      satisfactory, although it is significantly increasing; yet, this trend might
      worsen due to the shortage of funding. The collected data outline that in the
      three main national geographic areas, the distribution of funds and scientific
      productivity are markedly unbalanced.

PMID- 9289369
TI  - [A query system for the "SINTESI" database in scientific research and medical
      practice].
AB  - "SINTESI release 1.0" is an application for Windows that was designed to enable a
      practical approach to day-hospital evaluation and management of several metabolic
      and instrumental parameters. "SINTESI" provides electronic archives such as
      demographics, history, follow-up, laboratory, electrocardiogram, Doppler
      echocardiography, vascular echo-Doppler, Holter ECG, nuclear imaging, radiology,
      ergometric testing, ambulatory blood pressure monitoring, hemodynamics. We have
      improved the first release (1.0) with a new application that queries the database
      ("SINTESI release 2.0"). The new query application, developed in collaboration
      with experts of the Italian Group for the Study of Atherosclerosis and Metabolic
      Diseases, was designed with the central file displaying buttons that recall
      electronic archives, allowing to select the variables for the query. At the end
      of each operation, the user always returns to the central file, where it builds
      the query formula by "AND/OR" logic operators. Query formula and results can be
      recorded to be used whenever needed. The results of the query can be exported as
      DBF or ASCII files for analysis with statistical packages. This feature allows
      the use of the data bank for medical research.

PMID- 9289370
TI  - [Congenital arterio-venous coronary fistula associated with patent ductus
      arteriousus: description of a clinical case and review of the literature].
AB  - Congenital coronary artery fistulae are rare anomalies (0.27-0.4% of all
      congenital heart defects) and consist of a communication between a coronary
      artery and a cardiac chamber, a great artery or the superior vena cava. The
      association of these congenital anomalies with other congenital cardiovascular
      defects is unusual. The purpose of this paper is to report a case of congenital
      coronary fistula between the anterior descending coronary artery and the
      pulmonary artery associated with patent ductus arteriosus and to review the
      literature on the subject.

PMID- 9289367
TI  - [The effects of mid- and long-term administration (3-4 years) of carvedilol in
      patients with idiopathic dilated cardiomyopathy].
AB  - Carvedilol has been shown to determine a significant improvement in left
      ventricular function, symptoms, clinical course and prognosis of patients with
      chronic heart failure. However, these results were obtained in medium-term
      studies of < 1 year duration. We report the results obtained with long-term (3-4
      years) carvedilol administration to 40 patients with idiopathic dilated
      cardiomyopathy who were initially recruited in a 4-month double-blind placebo
      controlled trial. In the initial 4-month double-blind trial, 20 patients were
      randomized to placebo and 20 to carvedilol treatment. All patients, except one
      who was not on ACE-inhibitors, were on digoxin, furosemide and ACE-inhibitors.
      Carvedilol or placebo doses were progressively titrated, at weekly intervals, up
      to the maximal doses of 25 mg bid. After the initial 4-month double-blind phase,
      all patients were followed long term. Mean follow-up duration was 52 +/- 12
      months (range 48-61). Among the 20 patients initially randomized to carvedilol
      administration, 4 died (3 for cardiac and 1 for extracardiac causes) and 2
      underwent heart transplant. Among the 20 patients initially randomized to
      placebo, 5 died for cardiac causes, 3 underwent heart transplant and 4 were
      started on carvedilol because of progressive heart failure during the initial 4
      months of the study. The remaining 8 patients, who were kept on digoxin,
      furosemide and ACE-inhibitors, were used as control group. Each patient underwent
      an assessment of clinical conditions (NYHA functional classification and
      Minnesota Living with Heart Failure questionnaire), equilibrium radionuclide
      ventriculography, and maximal cardiopulmonary bicycle exercise testing. Exams
      were performed before treatment, after 4 and 12 months, and at the end of the
      follow-up period. No significant difference between the carvedilol and control
      group was present at baseline. Compared with baseline, patients in the control
      group presented a significant increase in left ventricular end-diastolic volume
      after long-term follow-up (from 126 +/- 62 to 138 +/- 43 and 158 +/- 52 ml/m2
      after 12 and 48 months, respectively). No significant difference, compared to
      baseline values, was noted. Patients on carvedilol presented a persistent
      improvement in left ventricular function. This was shown by the progressive
      increment in left ventricular ejection fraction from 22 +/- 6 to 34 +/- 11, 37 +/
      11 and 37 +/- 13%, after 4, 12 and 48 months, respectively (p < 0.001) with a
      concomitant reduction in left ventricular end-diastolic volume from 147 +/- 54 to
      101 +/- 44 ml/m2 at the end of the follow-up (p < 0.05). NYHA functional class
      remained significantly improved, in comparison with baseline (2.6 +/- 0.5 to 1.9
      +/- 0.3, 1.9 +/- 0.8 and 2.0 +/- 1.0 after 4, 12 and 48 months, respectively; p <
      0.01). Maximal functional capacity, assessed as peak VO2 was not significantly
      changed after 4 months (from 15.2 +/- 3.6 to 16.4 +/- 4.0 ml/kg/min) and showed a
      tendency towards a further improvement after 12 months and at the end of the
      follow-up (17.3 +/- 5.6 and 17.2 +/- 5.3 ml/kg/min, respectively). These results
      show that the favorable effects of carvedilol administration on left ventricular
      function and clinical symptoms are maintained also after long-term treatment.

PMID- 9289371
TI  - [Morphofunctional changes induced by acute pressure overload the isolated working
      rat heart].

PMID- 9289372
TI  - [Cardiopulmonary support in high-risk percutaneous coronary angioplasty].

PMID- 9289373
TI  - [Isolated systolic hypertension, a malady related to age].

PMID- 9289374
TI  - [Contrast echocardiography: current trends and future prospects].

PMID- 9289375
TI  - [The timing of surgical correction of mitral insufficiency].

PMID- 9289376
TI  - [The antagonistic effect of aspirin on the expression of prostaglandin
      participation in the antihypertensive activity of ACE inhibitors].
AB  - ACE-inhibitors antagonize both angiotensin production and bradykinin breakdown,
      resulting in enhancement of vasodilating prostaglandin release. This provides an
      explanation for the experimental observation that cycloxygenase blockers (such as
      aspirin or indomethacin) may counteract the antihypertensive efficacy of the ACE
      inhibitors; it may be also possible that hypertensive patients taking aspirin as
      an antiplatelet agent may fail to benefit from ACE-inhibition. This study was
      aimed at: evaluating the magnitude and incidence of the inhibitory phenomenon;
      defining the minimal aspirin dosage that produces an antagonistic effect, as well
      as the possible reasons for a different individual susceptibility. We have
      studied untreated patients with mild (10 cases, Group 1), moderate (16 cases,
      Group 2) or severe (26 cases, Group 3) hypertension. The ACE-inhibitor enalapril
      was used at doses of 10 mg bid (groups 1 and 2) or 20 mg bid (Group 3). Active
      drug treatment periods had a 5-day duration. A daily dose of aspirin of 100 mg
      had no effect on the antihypertensive efficacy of enalapril. On the contrary,
      when a dose of 300 mg was used, 60, 57 and 50% of patients in Group 1, 2 and 3,
      respectively, showed a > 20% restraint of the mean arterial pressure fall with
      enalapril (20% was the lower arbitrary limit for defining antagonism). Inhibition
      was independent of the sequence of drug administration. In these patients
      counteraction averaged 60, 70 and 90%, respectively. In them, and not in the
      remaining patients in each group, aspirin substantially attenuated the renin rise
      elicited by ACE-inhibition. These data suggest that: a dosage of 100 mg aspirin
      is devoid of any inhibitory effect; more that 50% of ACE inhibited patients are,
      at least in the short term, susceptible to the action of 300 mg aspirin,
      regardless of the severity of hypertension; counteraction is seemingly mediated
      through a prostaglandin inhibition and depends on the individual predominance of
      prostaglandin activation (also as a renin secretory stimulus) or angiotensin
      inhibition by the ACE-inhibitor.

PMID- 9289377
TI  - [Evaluation of left ventricular function in patients with mammary carcinoma after
      treatment with epidoxorubicin using a high-dose, short-term protocol].
AB  - Anthracyclines are effective chemotherapeutic agents against various malignancies
      but their therapeutic value is limited by well-known dose-related cardiotoxicity,
      mainly induced by oxygen free radicals. Left ventricular diastolic and systolic
      functional abnormalities precede the clinical evidence of cardiotoxicity. The aim
      of this study was to evaluate the possible cardiotoxicity of epidoxorubicin
      administered as "high-dose short-term" protocol. Twenty patients (mean age 50.4
      +/- 7.9 years) without cardiac disease, affected by advanced breast cancer were
      studied. All patients were treated with epidoxorubicin as neoadjuvant
      chemotherapy according to the new protocol "high-dose short-term" (cumulative
      dose 475.8 +/- 35.6 mg/m2, range 450-600 mg/m2, in 4-6 weeks). The effectiveness
      of cancer chemotherapy was monitored by clinical evaluation and mammography
      performed before and after treatment. All patients underwent color Doppler
      echocardiography and resting radionuclide angiocardiography in baseline condition
      and 30 +/- 10 days after the last cycle of chemotherapy. All patients showed a
      significant reduction of tumor lesion after chemotherapy. Left ventricular
      systolic and diastolic function parameters obtained by echocardiography
      (fractional shortening 33.1 +/- 4.5% vs 32.4 +/- 4.8%; ejection fraction 63.6 +/-
      6.2% vs 62.9 +/- 5.7%; E/A ratio 1.73 +/- 0.64 vs 1.82 +/- 0.67; E wave
      deceleration time 204 +/- 24.6 ms vs 208.5 +/- 31.7 ms;isovolumetric relaxation
      time 79 +/- 15.7 ms vs 80 +/- 17.8 ms) and radionuclide angiocardiography
      (ejection fraction 62.4 +/- 7% vs 61.8 +/- 5.9; peak ejection rate 2.87 +/- 0.44
      VTD/s vs 2.74 +/- 0.46 VTD/s; peak filling rate 2.72 +/- 0.54 VTD/s vs 2.6 +/-
      0.58 VTD/s) did not show significant changes after treatment. In conclusion, our
      results suggest that epidoxorubicin administration using the "high-dose short
      term" protocol in patients with breast cancer does not induce early significant
      abnormalities of left ventricular systolic and diastolic function.

PMID- 9289378
TI  - [Stress echocardiography with dobutamine in the identification of coronary
      disease in patients with left bundle branch block].
AB  - Left bundle branch block does not permit an easy diagnosis of coronary heart
      disease (CAD) with provocative non-invasive test such as bicycle or treadmill
      stress test. Echocardiography allows the identification of segmental wall motion
      by evaluating the movement as well the thickness of the segment examined. Due to
      its agonist action on beta 1 receptors, dobutamine causes an increase in
      myocardial oxygen consumption and, as a consequence, may reveal myocardial
      ischemia; on this basis, we evaluated the sensibility, specificity and diagnostic
      accuracy of dobutamine stress-echo in identifying CAD in patients with left
      bundle branch block, and compared results with those obtained from coronary
      catheterization. From February 1994 to September 1995 we observed 25 patients
      with left bundle branch block (17 men, 8 women, mean age 61.8 +/- 8.4 years,
      range 43.75), affected or suspected for CAD. All patients underwent dobutamine
      stress-echo test and coronary arteriography. We divided patients into two groups:
      the first one (11 patients) with acute myocardial infarction, the second one (14
      patients) without previous ischemic episodes. Diagnostic accuracy, specificity
      and sensibility of the stress-echo test were evaluated in order to identify
      significant stenosis of the left anterior descending (LAD), right coronary (RCA),
      and/or circumflex artery (CA). Dobutamine stress echocardiography showed in all
      patients, from basal to peak, an increase in blood pressure (from 121.2 +/- 17.4
      to 141.8 +/- 23.6 mmHg), heart rate (from 81.3 +/- 10.9 to 140.7 +/- 8.9 b/min),
      and double product (from 9861.1 +/- 1898.1 to 19976.6 +/- 3603.6). In 8 (32%)
      patients who had typical chest pain, 7 had CAD. In 17 (68%) patients without
      chest pain, 5 had CAD and 12 had normal coronary arteries. Dobutamine stress
      echocardiography showed segmental wall motion variations only in 13 patients; 12
      of them had a significant stenosis of coronary artery relative to the ischemic
      area, the other 1 was a false positive. Coronary arteriography showed stenosis of
      LAD in 10 and of RCA and/or CA in 12 patients, in both groups dobutamine stress
      echo test had 1 false negative. Dobutamine stress echocardiography showed high
      diagnostic value as a provocative non-invasive test for CAD in patients with left
      bundle branch block. In conclusion, or study shows that no statistical difference
      exists in identifying ischemia in identifying ischemia in the LAD territory
      compared to RCA and/or CA. Further investigations are need to confirm the higher
      diagnostic accuracy in patients with left bundle branch block and to establish
      whether lower specificity in patients with a previous myocardial infarction is
      due to the smaller number of patients or to methodology.

PMID- 9289379
TI  - [Changes in serum levels of N-terminal procollagen type III propeptide as an
      index of postinfarction ventricular remodeling].
AB  - The levels of aminoterminal propeptide of type III procollagen (PIIINP) can be
      used as an index of collagen breakdown. The aim of our study was to evaluate
      modifications in serum concentration of PIIINP (PIIINPs) in patients with a first
      episode of myocardial infarction. We examined 70 patients admitted at our
      Institution for acute myocardial infarction and 10 normal subjects. PIIINPs
      dosage was obtained by radioimmunoassay method utilizing a commercial available
      kit. All patients underwent three PIIINPs dosages: within 24 hours after
      admission, at 6 and 12 months after myocardial infarction. Control values were
      0.4 +/- 0.1 U/ml. In 38 patients (Group I) PIIINPs levels increased at 6 and 12
      months after infarction: 0.53 +/- 0.2, 0.75 +/- 0.2 and finally 0.76 +/- 0.1
      U/ml. In the remaining 32 patients (Group II) PIIINPs values increased at 6
      months and then returned to baseline at 12 months: 0.56 +/- 0.2, 0.75 +/- 0.1 and
      then 0.46 +/- 0.1 U/ml. The end-diastolic volume index did not change
      significantly in Group I (from 93.7 +/- 21 to 79.7 +/- 20 ml/m2) while it
      decreased after 12 months in Group II (from 88.9 +/- 13 to 58.6 +/- 11 ml/m2;
      confidence interval 95% from 2 to 55 ml/m2; p = 0.03). Similarly, there was no
      significant variation in end-systolic volume index (ESVI, from 39.7 +/- 11 to
      36.9 +/- 11 ml/m2) and ejection fraction (from 60 +/- 10 to 59 +/- 15%) in Group
      I; while in Group II ESVI decreased significantly (from 33.6 +/- 13 to 20 +/- 5
      ml/m2, confidence interval 95% from 3 to 24 ml/m2; p = 0.02) and ejection
      fraction improved (from 62 +/- 11 to 72 +/- 15%; confidence interval 95% from -20
      to -1%; p = 0.04). In conclusion, patients with elevated levels of PIIINPs at 12
      months did not improve ventricular function while patients with PIIINPs returning
      to baseline at 12 months had an improvement. Our results suggest an active
      participation of newly formed collagen in post-infarct ventricular remodeling.
      Therefore PIIINPs may be a marker of this process.

PMID- 9289380
TI  - [Silent myocardial infarction in a patient treated with radiation therapy and
      polychemotherapy for Hodgkin's lymphoma].
AB  - A 48-year-old woman with no cardiovascular risk factors was admitted to the
      hospital because of acute dyspnea. At 27-year-old, she developed Hodgkin's
      disease, that was successfully treated with splenectomy, combined chemotherapy
      (nitrogen mustard, vincristine, procarbazine, prednisone-MOPP regimen) and
      radiotherapy (4500 rads). At 43-year-old the lymphoma relapsed and she had
      further chemotherapy with doxorubicin, bleomycin, vinblastina and dacarbazine.
      After this treatment, she had an episode of pulmonary edema, attributed to
      doxorubicin acute cardiotoxicity. She responded to digitalis and diuretics and
      was discharged with an electrocardiogram (ECG) showing left bundle branch block
      and a normal echocardiogram. The patient enjoyed good health for several years
      and 4 months before the present admission the ECG and echocardiogram were
      unchanged. On this admission there were signs of left ventricular failure with
      acute pulmonary edema, and a new soft apical murmur (3-4 Levine). The patient
      required endotracheal intubation and high doses of diuretics, digitalis and
      vasodilators. The cardiac enzymes were negative, the serial ECGs confirmed left
      bundle branch block, while the echocardiogram showed moderate to severe mitral
      regurgitation, akinesia of the interventricular septum and inferior wall with
      dilation of the left ventricle. A previous silent myocardial infarction was
      suspected. After recovery, she underwent cardiac catheterization confirming
      akinesia of the interventricular septum and inferior wall with moderate mitral
      regurgitation, while coronary angiography showed a critical ostial stenosis of
      the right coronary artery. In view of a dipyridamole-thallium scan negative for
      myocardial viability, reperfusion was not attempted. With changes in
      radiotherapeutic techniques, the incidence of radiation-induced heart disease
      (pericarditis, myocarditis, conduction abnormalities and, rarely, occlusive
      coronary artery disease) is declining. Nevertheless, after irradiation of the
      chest and mediastinum a longterm cardiological follow-up is useful in selecting
      patients at higher risk of radiation-induced coronary artery disease, who will
      eventually require coronary angiography and reperfusion intervention.

PMID- 9289382
TI  - [The implantable automatic defibrillator: state of the art].

PMID- 9289381
TI  - [Hemodynamic effects of continuous intrathecal infusions of clonidine from a
      telemetric pump].

PMID- 9289383
TI  - [The heart of philosophers].

PMID- 9289384
TI  - Commentary on Reinhold Haux: aims and tasks of medical informatics.

PMID- 9289385
TI  - Editorial commentary: aims and tasks of medical informatics.

PMID- 9289386
TI  - Aims and tasks of medical informatics--a commentaryon Reihnold Haux's paper.

PMID- 9289387
TI  - Distance-based approaches to protein structure determination III. Copenhagen,
      Denmark, 5-8 November 1996.

PMID- 9289388
TI  - Incidence of anti-mouse antibodies in thrombocytopenic patients with autoimmune
      disorders.
AB  - Idiopathic thrombotycopenic purpura (ITP) is an autoimmune disorder in which
      circulating autoantibodies react with target antigens on the platelet membrane.
      In order to identify the autoimmune response in ITP, two MAIPA (Monoclonal
      Antibody (MAb) Immobilization of Platelet Antigen) assays (MAIPA I and MAIPA II)
      were performed on sera from thrombocytopenic patients. In the classic MAIPA assay
      (MAIPA I), control platelets were incubated simultaneously with human serum and a
      mouse MAb to a platelet glycoprotein. In MAIPA II, the control platelets were
      incubated first with the human serum and then, after washing, with the selected
      mouse MAb. A positive MAIPA I test but a negative MAIPA II has been shown to
      result from the presence of serum antibodies recognizing mouse MAb to platelet
      glycoproteins used in the assay. We compared the frequency of such 'anti-mouse'
      antibodies in patients with thrombocytopenia associated or not with other
      autoimmune states and in healthy donors with a normal platelet count.
      Statistically significant differences were found in the incidence of anti-mouse
      antibodies between patients and healthy donors. Furthermore, the identity of the
      targeted mouse MAbs varied in sera from the patients. The detected anti-mouse
      antibodies may include anti-idiotypic antibodies produced against cross-reactive
      idiotypes shared by human and mouse anti-platelet antibodies.

PMID- 9289389
TI  - Anti-tumor activity of monoclonal antibody CIBCNSH3 generated to the human EGF
      receptor.
AB  - The overexpression of the human epidermal growth factor receptor (EGFR) has been
      demonstrated in many malignancies like squamous cell carcinoma of the head and
      neck, cervix, breast etc. which are most prevalent in India. This is often
      associated with poor prognosis and high mortality in these patients. Monoclonal
      antibodies generated against EGFR which inhibit binding of ligands like EGF to
      their receptor have anti-tumor activity and hence therapeutic application. One
      such monoclonal antibody designated as CIBCNSH3 generated in our laboratory has
      been found to recognize an epitope in the extracellular domain of EGFR by
      immunoprecipitation. By immunoperoxidase test this antibody exhibited strong
      reactivity to EGFR in head and neck cancers and breast cancers studied. It also
      inhibited the binding of Epidermal Growth Factor (EGF) to its receptor on MDA
      MB468 breast cancer cells rich in EGFR as revealed by competitive binding assay
      using 125I EGF, indicating its anti-tumor activity. The in vivo therapeutic
      efficacy has been demonstrated by injecting i.p. into tumor bearing mice 200
      micrograms of the antibody for 4 consecutive days and then 100 micrograms twice a
      week resulting in complete regression of tumors of initial tumor size of 0.5-1.0
      cm diameter. These results were compared with a control antibody against EGFR and
      also a nonspecific antibody which were administered to different groups of
      animals. In vivo studies performed using cell lines in culture like MDA MB468,
      MDA MB157 and HN5 with overexpression of EGFR revealed 98% cell death when
      incubated with different concentrations of the antibody. This monoclonal antibody
      seems to have a promising future application as therapeutic agent for tumors
      which overexpress EGFR.

PMID- 9289390
TI  - Human monoclonal antibodies to viral peptides.
AB  - A new approach to the developing of human monoclonal antibodies to viral peptides
      is described. The method is based on the positive selection of B cells specific
      to viral peptides from normal human tissues. To isolate B cells bearing
      immunoglobulin receptors specific to viral epitopes magnetic beads coated by
      viral peptides were used. Human B lymphocytes specific to the neutralizing
      epitope of gp120 of human immunodeficiency virus and to the major epitope of
      Epstein-Barr nuclear antigen-I were isolated from freshly removed human tonsils.
      Preselected cells were transformed by Epstein-Barr virus and cultivated on
      irradiated human embryonic lung fibroblasts in RPMI 1640-OptiMEM medium with 10%
      fetal calf serum and all necessary supplements. The cultures of B cells producing
      antibodies to viral epitopes used for selection were obtained. Two cultures
      secreting IgM antibodies to the peptide MN-24 (neutralizing epitope of
      immunodeficiency virus) and to the peptide p107 of Epstein-Barr nuclear antigen-1
      were expanded, and the specificity of the antibodies and antibody-producing cells
      was analyzed. The method of positive selection of B cells specific to viral
      peptides may be used for the preparation of human monoclonal antibodies to viral
      antigens.

PMID- 9289391
TI  - The emerging concept of pathogenic natural autoantibodies.
AB  - Natural autoantibodies (NAA) are self-reacting antibodies found in the serum. NAA
      do not require antigenic or mitogenic stimuli for their synthesis. These low
      affinity antibodies are found in the sera of normal healthy subjects and animals
      and are thought to constitute part of the innate immunity by providing a first
      line of defense against foreign invading pathogens. In this paper we summarize
      the recently accumulated data which points to the pathogenic potential of NAA,
      challenging the paradigm of nonharmful antibodies.

PMID- 9289392
TI  - The role of the fetal immune system in the pathogenesis of RhD-hemolytic disease
      of newborns.
AB  - Data in the literature and author's research regarding the role of the immune
      reaction of fetuses and newborns in the pathogenesis of RhD conflict and
      hemolytic disease of newborns was analyzed. In this disease, the immune response
      of fetuses and newborns is shown to develop under the effects of maternal
      antigens, including RhD IgG, which cross the placenta. One of the results is the
      formation of immune complexes (ICs) between the maternal antigens and fetal IgM.
      In the intensive immune reaction, these ICs are removed from the infants at a
      high rate. As a result, the intensity of erythrocyte destruction, the degree of
      anemia and hyperbilirubinemia decrease. Various forms of HDN are of different
      intrauterine duration: from a few days in the icteric form without anemia to a
      month or more, in the hydropic form. In the latter form, decompensation of the
      immune system develops; extravascular erythroclasia by macrophages is replaced by
      intravascular lysis of erythrocytes. We suggest some methods to determine the
      fetal condition and a cure for the most severe cases of HDN, as well as a way of
      decreasing RhD-sensitization in women. These suggestions may be of interest to
      specialists in pediatrics and obstetrics and may be of clinical use.

PMID- 9289394
TI  - Immune stimulatory and anti-tumor properties of anti-CD3 and BAT monoclonal
      antibodies: a comparative study.
AB  - A novel monoclonal antibody raised to Daudi cell membranes was found to exhibit
      immune stimulatory and anti-tumor properties. The activity of this antibody (BAT)
      which also binds T cells was compared to that of anti-CD3. Anti-CD3 reacts with
      the T cell receptor complex, induces cell proliferation, and cytolytic activity
      in vitro and also manifests in vivo anti-tumor effect against murine tumors.
      Comparison of the two antibodies demonstrates similar induction in vitro of
      splenocyte proliferation and cytolytic activity. Both BAT and anti-CD3 antibodies
      manifest anti-tumor activity in mice bearing B16 melanoma. They differ however in
      the timing of antibody administration post-tumor inoculation which is most
      effective in eliciting the anti-tumor effect. Whereas BAT is most effective when
      administered 10 to 14 days post-tumor inoculation, anti-CD3 is effective at an
      early time. Data also indicate that BAT synergises with tumor cells in eliciting
      cell proliferation in vitro. In contrast, this effect could not be demonstrated
      with anti-CD3. The properties of BAT may be of advantage in its potential
      clinical use.

PMID- 9289393
TI  - The effects of T cell subpopulations and recombinant interleukin (IL)-2 on
      peripheral B cell function in patients with myasthenia gravis.
AB  - Myasthenia gravis is an autoimmune disease mediated by antibodies to
      acetylcholine receptors (AChR) of skeletal muscle. The production of anti-AChR
      antibodies has been shown to be T cell dependent. To elucidate the mechanism(s)
      of anti-AChR antibody production in myasthenic patients, we studied the effects
      of regulatory T cells and/or IL-2 on the differentiation of AChR-primed B cells,
      with use of AChR stimulation for the induction of anti-AChR antibodies in vitro.
      Our data suggest that CD8+ T cells possess some complicated functions. CD8+ T
      cells could not only provide help for B cells to secrete anti-AChR antibody, but
      also possibly inhibit response of CD4+ T cells or kill B cells, then repress anti
      AChR antibody production in MG patients. There might be some defect either in the
      number or function of CD8+ T cell in MG patients. Exogenous IL-2 could completely
      restore the suppression activity of CD8+ T cells in anti-AChR antibody production
      in vitro.

PMID- 9289395
TI  - Patient of client? If in doubt, ask.

PMID- 9289397
TI  - 37th Italian Congress of Nephrology. Cagliari, 29 May-1 June 1996. Abstracts.

PMID- 9289398
TI  - New therapeutic strategies for higher cure rates: high dose therapy and new
      therapeutic modalities. Proceedings of the 12th Bristol-Myers Squibb Nagoya
      International Cancer Treatment Symposium. Nagoya, Japan, 4-5 October 1996.

PMID- 9289396
TI  - Recent literature on cell stress & chaperones.

PMID- 9289400
TI  - Evolution of hydrothermal ecosystems on Earth (and Mars?). Proceeding of a
      symposium. London, January 30-February 1, 1996.

PMID- 9289399
TI  - [Two kinds of cytokine gene expression in umbilical cord blood of premature and
      mature neonates].
AB  - OBJECTIVE: To study the immunological function of premature and mature neonates.
      METHOD: By means of in situ hybridization technique, mRNA expression of
      interleukin-1 (IL-1) beta and IL-1r alpha in umbilical cord blood of 34 cases was
      analyzed. RESULTS: It showed that mRNA expression of IL-1 beta and IL-1r alpha
      were significantly lower in the group of preterm vaginal delivery resulting from
      premature rupture of membranes than that of preterm cesarean section with the
      indication of pregnancy induced hypertension and than that of full term delivery
      (P < 0.001). No significant difference was found between the latter 2 groups.
      CONCLUSIONS: It indicated that gene expression of IL-1 beta and IL-1r alpha
      probably related to the fetal maturity.

PMID- 9289401
TI  - [Frequency and etiology of calf losses and calf diseases before weaning in cow
      calf farms. II. Microbiological and parasitological diagnoses in diarrheic
      calves].
AB  - Diarrhea is the most frequently diagnosed disease in Swiss cow-calf farms. During
      an longitudinal study conducted in 105 cow-calf farms in Switzerland in 1993-95,
      blood and fecal samples were collected from diarrheic calves and from calves that
      died because of diarrhea. Campylobacter spp. were detected in 42%, E. coli (VTEC)
      in 32%, rotavirus in 33%, coronavirus in 13%, coccidia in 43% and helminths in 8%
      of the cases. In some samples Yersinia pseudotuberculosis were isolated. The BVD
      virus antigen was not detected in any of the calves examined. In most cases
      concurrent infection with several enteropathogens was diagnosed. Specific causes
      of diarrhea were therefore difficult to establish. The bacteriological findings
      of this study have implication for food safety: VTEC, Campylobacter spp. Yersinia
      spp. and cryptosporidia are considered as potential causes on zoonoses.

PMID- 9289402
TI  - [Reproductive toxicological fundamental investigations on adult male rats of the
      WIST/Lppt stock on the determination of swelling after administration of cadmium
      chloride].
AB  - The reproductive-toxic effects after an oral administration of Cadmium as Cadmium
      chloride on testes and epididymidis of mature Wistar rats were investigated.
      After daily dosages of 0.3, 0.6, 1.0 oder 2.0 mg CdCl2/kg b.w. over one or two
      weeks no changes of testes and epididymidis were detected in comparison with
      control animals by histological observations. By means of morphometrical methods
      significant changes of the testes from a dosage of 1.0 mg/kg b.w. and changes of
      the epididymidis previously a dosage of 0.3 mg/kg b.w. have been demonstrated.
      That means the effect level of Cadmium is higher by consideration of testes than
      of epididymidis. Consequently, during investigations of reproductive toxicity one
      hand to test both organs.

PMID- 9289404
TI  - Use of carbon-11 nicotine in PET studies.

PMID- 9289403
TI  - [Problematic aspects of breeding dwarf rabbits].
AB  - Some aspects of relevance for animal protection in breeding dwarf (pet) rabbits
      are enumerated and discussed. The predisposition of these standard dwarfs (Dw/dw)
      for certain defects and diseases underlines the partial dominance of Dw; mating
      of these heterozygous dwarfs is an open neglect of the German animal protection
      law (section 11b). For feasibility of control breeders (and especially so in
      commercial pet rabbitries) should be obliged to guarantee unambiguous
      identification of breeding animals and their progeny.

PMID- 9289405
TI  - [Simultaneous occurrence of cervicofacial an pleuropulmonary actinomycosis].
AB  - Successful treatment of rapidly spread cervicofacial and pleuropulmonary
      actinomycosis case is reported. Significant law destruction and pathological
      fractures were observed as well.

PMID- 9289406
TI  - [Stomatologic implications of Turner syndrome II. Orthodontic disorders and some
      characteristics of the temporomandibular joint].
AB  - Turner syndrome is a disease belonging to the group of chromosome disorders,
      which affect sexual chromosomes. The present study aims at analysing and
      describing orthodontic and TMI joint disorders in patients with Turner's
      syndrome, and comparing the results with those healthy controls. Data of 24
      patients with Turner's syndrome as well as 24 healthy controls were collected and
      analysed. No significant alteration in TMI was found in any of the two groups.
      Both groups presented orthodontic anomalies, however, crowding was the most
      common anomaly in the control group, whereas in the case of patients with
      Turner's syndrome, other anomalies (protrusion, open bite, cross bite) could also
      be found more frequently.

PMID- 9289407
TI  - [Prophylactic use of roxithromycin in dental procedures].
AB  - In this study roxithromycin was applied for prophylactic treatment of 104
      patients (implantology, dentoalveolar surgery, risk patients etc.) underwent
      dental surgery. The efficacy and side effects of roxithromycin were studied. The
      efficacy of this antibiotic was 92%, gastrointestinal complains, as the most
      common side effects were obtained in 2.8% of the patients treated with
      roxithromycin.

PMID- 9289408
TI  - Cloning and expression pattern of a second [His5Trp7Tyr8]gonadotropin-releasing
      hormone (chicken GnRH-H-II) mRNA in goldfish: evidence for two distinct genes.
AB  - Complementary DNAs (cDNAs) encoding [Trp7Leu8]GnRH (sGnRH) and [His5Trp7Tyr8]GnRH
      (cGnRH-II) peptides have been isolated from the brain of goldfish (X. W. Lin and
      R. E. Peter, 1996, Gen. Comp. Endocrinol. 101, 282-296). In the present study we
      report the isolation of a second cDNA encoding cGnRH-II peptide in the brain of
      goldfish using reverse transcription (RT) and rapid amplification of cDNA ends.
      There is an overall 79.7% nucleotide sequence similarity between the two cGnRH-II
      cDNAs, with 65.3, 91.2, and 76.3% similarity between the 5'-untranslated regions,
      coding regions, and 3'-untranslated regions, respectively, of the two cGnRH-II
      cDNAs. Comparison of the two cGnRH-II precursors shows 87.2% amino acid
      similarity. The presence of two cGnRH-II genes was confirmed by the sequence
      analysis of the introns between exon II and exon III of the two cGnRH-II genes.
      Results indicate that the intron of the two cGnRH-II genes shows a high
      divergence in size and sequence, but contains the same splice junction.
      Expression of the two cGnRH-II mRNAs was detected by RT-polymerase chain reaction
      assay and Southern blot analysis in all five grossly dissected brain areas,
      olfactory bulbs and tracts, telencephalon, hypothalamus, optic tectum-thalamus,
      and posterior brain. However, there was a difference in apparent intensity of
      hybridization signal for the two cGnRH-II mRNAs in all brain areas, suggesting a
      difference of expression levels. sGnRH mRNA was detected in the olfactory bulbs,
      telencephalon, and hypothalamus, but not in midbrain and posterior brain areas.
      The present finding of duplicate cDNAs and genes for cGnRH-II in goldfish is in
      agreement with the recent tetraploidization in this species.

PMID- 9289409
TI  - [Cloning of ribR, an additional regulatory gene of the Bacillus subtilis
      riboflavin operon].
AB  - A 13.0-kb EcoRI fragment of Bacillus subtilis DNA carrying an additional
      regulatory ribR gene of riboflavin operon was cloned on the basis of resistance
      to 7, 8-dimethyl-10 (O-methylacetoxym)-isoalloxasin. The cloned fragment was
      trans-dominant with regard to ribC constitutive mutations that block the
      overproduction of riboflavin but inactive relative to constitutive mutations in
      the rib(O) regulatory region.

PMID- 9289410
TI  - [The topological structure of the genetic code].
AB  - On the basis of the topological concept of the vicinity of the point, graphs of
      connectedness for four nitrous bases (L and D tetrahedra) and the topological
      patterns of doublet and triplet genetic codes were constructed. These topological
      patterns were isomorphic to Boolean hypercubes B4 and B6, respectively. The
      resultant structures of the genetic code resembled those obtained earlier in
      terms of the rhombic variant of the genetic code table, which was constructed on
      the basis of complementarity of the coding doublets. Specifically, both models
      assumed the following: (1) when two groups of doublets and quartets of triplets
      that coded for one amino acid or two amino acids each were transformed into each
      other according to Rumer's rule (C <--> A, G <--> U), they retained C2 symmetry,
      and (2) single transitions of nitrous bases changed the structures of the encoded
      amino acids to the minimum possible extent. A possible mechanism for the origin
      of the genetic code and the possibility of using the characteristics of the
      obtained structures to develop the algorithm of prediction of the supermolecular
      protein structure, read genetic "texts", and refine the functions of amino acids
      as molecular modules are discussed in terms of the results obtained.

PMID- 9289411
TI  - [Divergence between "early" genes from defective phages of various strains of
      soil bacilli, close to Bacillus subtilis 168].
AB  - The extent of xre gene divergence was studied in nine soil bacillus strains with
      different degrees of relationship to Bacillus subtilis 168. This gene product is
      a repressor of defective phages. Bac. subtilis 168 recipient strains were
      transformed by DNA from these bacillus strains for the xhi-1479 marker and ten
      markers of amino acid and nitrous bases metabolism. The efficiency of soil strain
      DNA hybridization with Bac. subtilis 168 DNA was assessed. Eight strains were
      close to Bac. subtilis 168 with respect to the efficiency of heterotransformation
      for all markers and hybridization, and one strain (1621) strongly differed from
      other strains with regard to these parameters. As determined by the degree of
      differences in heterotransformation for all markers, the nucleotide sequence of
      the xre gene diverged in the evolution process at a rate similar to that of the
      nucleotide sequences of the housekeeping genes. All examined genes were shown to
      have similar selective value.

PMID- 9289412
TI  - [Hyperrecombination of plasmids is characteristic for hyperresistant strains of
      Escherichia coli].
AB  - Intraplasmid recombination frequency was assessed in several Escherichia coli K12
      strains by the kinetic bioluminescence method. Enhanced plasmid recombination was
      observed in two mutant E. coli K12 strains, which were hyperresistant to DNA
      damaging agents, gamma-rays, photosensitizer 8-methoxypsoralen. Plasmid
      recombination frequency per one generation (P) was calculated. In mutant strains,
      this value was shown to exceed that in control isogenic strains with a standard
      resistance approximately by a factor of 15. Enhanced constitutive synthesis of
      specific proteins such as heat-shock proteins in Gamr444 and a 55-kDa protein in
      SA270 in hyperresistant mutant strains is assumed to promote activity of the
      recombinational RecF pathway system.

PMID- 9289413
TI  - [Genetic control of naphthalene biodegradation by a strain of Pseudomonas sp.
      8909N].
AB  - The ability of Pseudomonas sp. 8909N to grow using Naphthalene and salicylate as
      the sole source of carbon and energy is mediated by the presence of an 80-kb
      conjugative pBS1145 plasmid in this strain. Structural genes for naphthalene
      degradation in pBS1145 plasmid are homologous to those in the known NAH7 plasmid.
      Conjugational transfer of pBS1145 from the original strain is accompanied by a
      deletion of a plasmid DNA fragment that does not affect the Nah+Sal+ phenotype.
      Plasmid pBS1145 specifies a low constitutive level of catechol-2,3-dioxygenase,
      the key enzyme of the metha-pathway of catechol degradation. Activity of this
      enzyme is induced in the presence of salicylate. Enzymes of both the metha and
      ortho-pathway of catechol degradation (catechol-2-3-dioxygenase) were shown to
      operate in the process of naphthalene degradation in Pseudomonas sp. 8909N. The
      ability of this strain to bring about transformation of polycyclic aromatic
      hydrocarbon phenanthrene is also controlled by pBS1145 plasmid.

PMID- 9289414
TI  - [Associated changes in recombination length, number of exchanges, and
      interference in Drosophila chromosome 2].
AB  - A set of eight strains differing in recombinational length of the left arm of
      chromosome 2(2L) was obtained by means of inserting genetic material of the Y
      chromosome into the 34A region and two inversions, In(1)dl-49 + BM1 and In(3LR)D,
      demonstrating interchromosomal effects on crossing over. The length of 2L ranged
      from 15.0 to 64.9 cM. Interchromosomal effects on crossing over differed in
      extent and in distribution over 2L between females carrying wild-type chromosome
      2 and the chromosome with inserts. Tetrad analysis showed that the 2L
      recombinational length was increased up to the normal level (females +/+; +/+,
      +/+) or more due to increased proportions of single- or double-exchange tetrads,
      respectively. A model of pairing and crossing over proposed earlier was used to
      interpret crossing-over patterns. The model implies that initial pairing of
      homologous chromosomes involves the formation of local contacts between them. The
      number of exchanges in a bivalent is determined by the number of local contacts
      at the onset of an event termed the determination of crossing-over sites (DCS).
      Interference is determined by the mechanism of contact formation. The extent of
      interference varies both temporally and spatially (within a chromosome),
      decreasing from the periphery to a contact site as the time from contact
      formation increases.

PMID- 9289415
TI  - [Cyclic nucleotide phosphodiesterases in mutant lines of Drosophila
      melanogaster].
AB  - The activities of general phosphodiesterase and its Ca(2+)-calmodulin-independent
      from (PDE-1) were studied in strains mutant for the agnostic gene and in the
      strain Canton S. Enzyme activity was determined in males and homo- and hemizygous
      females of four strains. It was found that mutation at the agnostic gene resulted
      in increased PDE-1 activity. This effect appears to depend on the dose of the
      mutant gene, because it was revealed only in homozygous females. We have
      substantiated the notion that the agnostic gene controls calmodulin properties by
      virtue of encoding a calmodulin-inhibiting protein.

PMID- 9289416
TI  - [N-acetylation of biogenic amines in Drosophila virilis].
AB  - In adults of two Drosophila virilis lines displaying different genetically
      determined reactions to stress, N-acetyl-transferase (NAT) activity against
      substrates dopamine and octapamine was studied. Sexual dimorphism was
      characteristic of NAT activity when octapamine served as a substrate. However, in
      the case of dopamine, this phenomenon was not found. This suggests that two
      different enzymes with N-acetyltransferase activities exist in D. virilis. The
      flies of the studied lines were not shown to be indistinguishable in both enzyme
      activities. Short-term stress (38 degrees C for 30 and 60 min) did not affect NAT
      activity in flies of either studied line.

PMID- 9289418
TI  - [Increase in the effectiveness of using inbreeding in pedigree stocks of dairy
      cattle].
AB  - At the main Russian bloodstock farms improving Black-Pied cattle, the influence
      of inbreeding level on pedigree and reproductive characteristics of animals was
      studied. Inbreeding patterns with the highest selective effect were revealed.
      Mothers were found to have an increased effect on milk productivity of daughters
      obtained from close inbreeding. Recommendations for improving breeding strategy
      are given.

PMID- 9289417
TI  - [Cytogenetic and cytobiophysical study of temperature adaptation and heterosis
      mechanisms in Drosophila melanogaster Meig].
AB  - The degree of polyteny of giant chromosomes and electrokinetic properties of cell
      nuclei salivary glands of Drosophila melanogaster were studied in relation to
      genotype and rearing temperature. Inbred and selected Drosophila lines and
      interlinear F1 hybrids were used. The experiments were conducted in three
      temperature regimes: 25 (control), 18, and 28 degrees C. At low (18 degrees C)
      and high (28 degrees C) temperatures, the degree of polyteny and number of
      electronegative nuclei was respectively higher and lower than in the control. The
      correlation of these parameters with a number of adaptive traits was studied. The
      results suggest that chromosome polyteny and nuclear electrokinetic potential
      play a significant role in heterosis and adaptation of Drosophila melanogaster to
      adverse temperatures.

PMID- 9289419
TI  - [Chromosomal polymorphism in mole rat Spalax microphthalmus (Rodentia,
      Spalacidae) from results of differential staining].
AB  - Differential stained chromosomes of the mole rat Spalax microphthalmus Guld.
      (Rodentia, Spalacidae) (2n = 60; NF = 110-112) from Streletskaya and Kazatskaya
      steppes (Kurskaya oblast, Russia) are described. Animals heterozygous for a
      complex chromosome rearrangement resulting in increased chromosome size and
      altered location of the centromere were revealed.

PMID- 9289420
TI  - [Activity of the embryonal genome of mink during diapause (cytogenetic analysis):
      number of cells and cell nucleus size in blastocysts or various size and age].
AB  - The number of cells and the morphology and size of the nuclei of these cells in
      diapausal mink embryos were investigated. Growth of blastocysts from 0.25 to 1.2
      mm in diameter in the complete absence of classical mitoses is accompanied by an
      increase in the average number of cells per embryo from between 100 and 150 to
      2000, respectively; diameters of cell nuclei vary from 6 to 19 and from 6 to 53
      micron, respectively. Some giant nuclei exhibit morphological signs of polyteny.
      In all nuclei, the number of active (silver-stained) nucleoli does not exceed
      that of nucleolar organizers in the mink diploid genome. The obtained results,
      combined with data from the literature, allow the inference that polytenization
      of trophoblast cells followed by cryptic segregation of genomes provides the key
      mechanism for rapid growth of diapausal blastocysts.

PMID- 9289421
TI  - [DNA genotyposcoy in determining paternity: use of hybridized probes].
AB  - Analysis of hybridization probes for DNA genotypescopy (DNA genotyping and genome
      fingerprinting) was performed to detect 21 cases of paternity testing. A system
      with the highly informative multilocus DNA probe Red4, isolated by us earlier,
      and two single-locus probes (YNH24 and CMM101) detecting highly polymorphic (H >
      96%) loci D2S44 and D14S13 was tested. In the cases analyzed, the Red probe was
      shown to detect, on average, 19.28 +/- 3.6 polymorphic BsuRI fragments in the DNA
      profile of presumable fathers and 19.67 +/- 5.84 BsuRI fragments in the DNA
      profile of mothers. The average number of DNA fragments inherited by a child from
      either parent was approximately equal (8.72 +/- 3.77 and 7.11 +/- 2.66,
      respectively). The low population frequency of DNA fragments detected by the Red4
      probe allowed highly effective positive paternity identification to be performed.
      Paternity was established in 86% (with probability > 99.75 or > 99.99%) and
      excluded in 14% of expertises. Single-locus probes YNH24 and CMM101 were used as
      an additional criterion in cases when, in the DNA profile of a child, a single
      band (probable de novo mutation) or several bands (probable false paternity or
      maternity) were revealed but absent in both presumable parents. In once case, a
      de novo mutation for the YNH24 probe, not described earlier, was revealed.
      Therefore, a combination of multilocus and single-locus hybridization probes
      appeared to be the most promising method for significant paternity testing in
      forensic and medical genetic practice.

PMID- 9289422
TI  - [Hereditary nervous system diseases in Mordovia].
AB  - A medical genetic study on hereditary neural diseases was performed in 21
      districts of the Mordovian Republic. The total number of persons examined was
      936,800. The population load of autosomal dominant, autosomal recessive, and X
      linked recessive diseases was 0.1696 +/- 0.0129, 0.1075 +/- 0.0107, and 0.0341 +/
      0.0010, respectively. Twenty-eight disease entities were revealed, including 10
      autosomal recessive (AR), 15 autosomal dominant (AD), 2 X-linked recessive (XR)
      diseases, and 1 genetically heterogenous disease. These diseases were
      nonuniformly distributed among different populations of Mordovia. The incidence
      of AR diseases was highest in the Mordovian and Tatar populations; that of AD
      diseases, in the Russian population; and that of XR diseases, in the Mordovian
      population.

PMID- 9289423
TI  - [Resistance to hunger as an element of the adaptive strategy of malaria mosquito
      larva].
AB  - Mortality from starvation in larvae of malaria mosquito species Anopheles
      beklemishevi, A. messeae, and A. sinensis (Diptera, Culicidae) was compared. The
      results showed that the southern species. A. sinensis is more resistant to
      starvation and more competitive than A. messeae, the species with chromosome
      polymorphism. Mortality of larvae increased when they starved in groups. Starving
      A. messeae larvae with "southern" inversions (K-strategists) proved to be more
      viable than larvae with "northern" karyotypes (r-strategists). The relationship
      between resistance to starvation and selection strategies in malaria mosquito
      populations is discussed.

PMID- 9289425
TI  - [Induction of cytogenetic damage to rat bone marrow cells by combined exposure to
      chronic and acute gamma radiation].
AB  - The combined influence of various doses of chronic irradiation (0.029 Gy/day)
      followed by acute irradiation at doses of 4 and 6 Gy (0.47 Gy/min) on the
      frequency of chromosomal aberrations in rat bone-marrow cells was studied. A
      pronounced adaptive response was observed at all doses of chronic irradiation
      followed by acute irradiation.

PMID- 9289424
TI  - [A rare case of chromosome mutation in the ground vole Terricola majori
      (Arvicolinae, Rodentia)].
AB  - A rare case of chromosome variability is described for the ground vole, Terricola
      majori, from the Lagodekhi Nature Reserve (Georgia). This species is
      characterized by a stable karyotype (2n = 54, NF = 60), but we found an animal in
      which 2n = 53, NF = 60. The change in the diploid number resulted from a
      Robertsonian translocation accompanied by a local amplification of satellite
      sequences in centrometric heterochromatin. This structural rearrangement is
      probably a neutral mutation and is described for forest T. majori voles for the
      first time.

PMID- 9289426
TI  - [A simple method of selecting Saccharomyces cerevisiae ade1 and ade2 mutants].
AB  - A simple technique of selection for spontaneous red mutants of yeast
      Saccharomyces cerevisiae is proposed. It is based on incubation of yeast cells
      carrying a deletion in the GCN4 gene on a solid selective medium containing 3
      amino-1, 2, 4-triazole (3AT). After incubation for three weeks at 30 degrees C,
      the 3 AT-resistant mutants ade2 and ade1 were easily visualized due to the pink
      or red colony color; they were then selected and analyzed by genetic and
      biochemical methods. The frequency of these colored mutants was approximately 10
      9. The method proposed is shown to be suitable for selection and analysis of both
      spontaneous mutants ade2 and ade1 and those induced by various mutagens. The
      possible molecular mechanism of 3AT-resistance of red mutants is discussed. This
      mechanism involves GCN4-independent activation of expression of genes of purine
      and histidine metabolism. This activation results from purine starvation caused
      by arrest of purine biosynthesis the ade2 and ade2 mutations.

PMID- 9289427
TI  - [Lipid metabolism in women with threatened abortion].
AB  - The study group consisted of 130 subjects: 50 healthy nonpregnant, 35 healthy
      women in the I trimester of gestation (gestational age 6-15 weeks) and 45
      patients with symptoms of threatened abortion (the same gestational age). In the
      latter group pain and bleeding ceased after hormonal treatment and spasmolytic
      drugs. Serum blood concentration of following compounds were determined: total
      lipids, LDL fraction, total cholesterol, phospholipids, triglycerides, HDL and
      LDL cholesterol fractions. Threatened abortion had changed lipids profile;
      diminished concentrations of LDL fraction, total cholesterol, LDL cholesterol
      fraction and phospholipids were observed. Levels of total lipids, phospholipids
      and triglycerides++ in blood serum of healthy pregnant women in the I trimester
      of gestation were higher than in nonpregnant women.

PMID- 9289429
TI  - [Ultrasonographic examination of the newborn brain in various states of perinatal
      risk].
AB  - A group of 91 neonates born in different states of the perinatal risk was
      analysed. During the ultrasonography testing of the brain the intracranial
      bleeding was stated. The dominant risk factors of the occurring of bleeding were
      EPH gestosis, preterm rupture of the membranes, operative delivery and the
      immaturity of the immaturity of the child.

PMID- 9289428
TI  - [Homeostasis of calcium-phosphorus-magnesium in women with pregnancy induced
      hypertension].
AB  - Study group consisted of 63 women in the III trimester of pregnancy (gestational
      age 29-40 weeks). 32 subjects with PIH (investigated group) were compared to
      control group consisted of 30 healthy patients with uneventful course of
      gestation. Women with PIH had no proteinuria nor oedema, their mean blood
      pressure remained at the level of 161 +/- 16.7/98 +/- 12.8 mm Hg. Concentration
      of calcium, phosphorus and magnesium in serum blood and urine were determined. It
      was stated that due to renal impairment observed during PIH, calcium urine
      excretion and calcium concentration in blood serum are decreased while serum
      inorganic phosphorus levels are increased. No changes in magnesium and ionised
      calcium homeostasis were seen in the course of PIH.

PMID- 9289430
TI  - [GnRH analogs for treatment of ovarian cancer].
AB  - To make use of antigonadotropin and antiproliferating action of the synthetic
      analogs of GnRH there was applied this decapeptide in 33 patients with ovarian
      cancer who were treated traditionally by chemotherapeutics PAC and radiotherapy.
      The monitoring of treatment was supported on the clinical opinion of the whole
      and locally state of health, the USG examinations of pelvic and diaphragm, the
      measure of level of CA-125 and second-look operations. There were got
      statistically characteristic rise of remissions and stabilizations of neoplastic
      process.

PMID- 9289431
TI  - [Changes in activity of alpha amylase and its salivary isoenzyme in serum and
      urine after surgical treatment of ovarian neoplasms].
AB  - Serum and urinary activity of alpha-amylase and isoamylase salivary was assessed
      in 40 patients with different types of ovarian cancer. The measurements were
      performed before surgical procedure and the 7th day after surgical removal of the
      tumor. Significant increases activity was found in patients with serosal ovarian
      cancer p < 0.001. On the 7th day after operation the activity of alpha-amylase
      and her of isoenzyme salivary reached control values.

PMID- 9289432
TI  - [Intracavitary brachytherapy method using after-loading for treatment of women
      with endometrial uterine neoplasm].
AB  - We would like to introduce intracavitary brachytherapy using double rod-shaped
      applicators. The women who are treated with this method are evaluated in III FIGO
      stage and the patients in stage I and II who could not undergo the operation.
      This method allows to distribute equally the dose in whole uterus, insertion of
      the applicators is not difficult. The brachytherapy treatment is well tolerated.

PMID- 9289433
TI  - [Primary nontrophoblastic tumors of the placenta].
AB  - Looking from histogenetical point of view primary neoplastic alterations of
      placenta and umbilical cord can be divided in two main groups. First group
      consists of neoplasms of trophoblastic disease's origin: placental site
      trophoblastic tumor, choriocarcinoma and hydatidiform mole, according to most
      authors it not belonging to neoplasms. The second group consists of
      nontrophoblastic tumors, like: chorioangioma and teratoma. Hepatocellular adenoma
      and leiomyoma are also enclosed to the nontrophoblastic tumors. It hasn't been
      defined yet whether all nontrophoblastic changes in placenta or in umbilical cord
      should be considered as neoplasms or like pseudoneoplastic changes. Comparing to
      neoplasms of trophoblastic disease's origin nontrophoblastic tumors are not
      frequent changes to be observed, moreover they are always benign tumors. In some
      cases these neoplasms are asymptomatic, however clinical course of some of them
      may become severe. The influence of nontrophoblastic tumors on pregnancy and
      delivery is often underestimated. It could be observed that studies on these
      neoplasms are performed very seldom what may be result of their infrequent
      appearance and because of their asymptomatic natural history. In this study we
      presented an up-to date opinions about the histopathogenesis of the
      nontrophoblastic tumors and also their histopathological characteristics and the
      most common symptoms which can accompany the development of these neoplasms. An
      important notice is that these tumors can remain undetected during macroscopic
      examination of secundines.

PMID- 9289434
TI  - [Spontaneous rupture of the pregnant uterus in a primipara as an unusual
      complication of previous salpingectomy].
AB  - The case of spontaneous rupture of uterus in 38th week of pregnancy in a 24 year
      old primipara is describe. The rupture was localized the site of dexon sutures
      applied during left salpingectomy performed because of ectopic pregnancy nine
      months ago. Diagnosis was made during cesarean section performed as a life saving
      procedure. Conservative repair of uterus resulted in uneventful recovery of the
      patient.

PMID- 9289435
TI  - [Chondrosarcoma of the small pelvis imitating an ovarian tumor].
AB  - The authors present diagnostic-therapeutic record concerning chondrosarcoma-tumor
      in 41-year-old women operated on ovary-tumor. They point out the rareness of
      chondrosarcoma within pelvis, the diagnostic and therapeutic difficulties and
      relapses into illness after radical remove of tumour without pelvis bones
      resection.

PMID- 9289436
TI  - [Obstruction of biliary tracts in infants].
AB  - Three cases with the biliary tracts obstruction in infants are reported. Similar
      early clinical symptoms were subsequently distinguished by the serious of the
      diagnostic examinations. That allowed for undertaking proper treatment. The
      prognosis in congenital biliary tract obstruction depends on the child's age time
      of the operation and in the cases of the inflammatory ethiology depends on the
      proper antibiotic therapy.

PMID- 9289437
TI  - [Body weight distribution norms of newborns and fetuses with a gestational age
      with 28 weeks or more].

PMID- 9289438
TI  - [Graphic modification of the Ballard-Klimek scale].
AB  - 95% of mature newborns have 39 +/- 3 points in the new Ballard-Klimek after labor
      and delivery in the normal range of birth occurrence. It means that in the range
      starting from 37 0/7 to 43 2/7 gestational week there is no linear increase from
      30 to 50 points of Ballard scale.

PMID- 9289442
TI  - [Cervix neoplasms in women younger than 36 years of age].
AB  - Between 1970 and 1986, 252 women under 36 years of age with cervical carcinoma
      were treated in the Center of Oncology in Cracow. The five-year disease-free
      survival for all patients was 52.8%. In the multivariate analysis tumor stage IIB
      and III and the age under 30 years were adverse prognostic factors.

PMID- 9289439
TI  - [Radioimmunologic methods for determining cortisol binding globulin-CBG in human
      serum].
AB  - The authors described double antibodies radioimmunoassay of human cortisol
      binding globulin serum level in support of previous isolated and purified
      trancortin and anti-transcortin antibodies produced by rabbit immunization.
      Antigen was iodinated by chloraminet method and purification on Ultragel AcA 54
      column. Standard curve had specific Bx/Box100%. Using described method
      investigation of transcortin globulin serum level is precise and repetitive.

PMID- 9289441
TI  - [Usefulness of clinical evaluation for the level of CA-125 antigen and
      ultrasonographic color Doppler examination in diagnosis of ovarian tumor].
AB  - The objective of our study was to evaluate the predictive value of serum CA-125
      levels and transvaginal ultrasound with color Doppler flow mapping (RI) in
      patients with benign and malignant ovarian tumors. The retrospective analysis
      included 78 women in whom 92 tumors were detected. Eleven patients had ovarian
      carcinoma (a total of 16 tumors). Predictive values were compared for tumor
      morphology, lowest resistive index (RI) < 0.40 and CA-125 > 35 IU/ml.
      Sensitivity, specificity, positive and negative predictive values in
      differentiating malignancy were highest for RI (94%, 87% 87% and 94%,
      respectively). Morphological criteria or CA-125 levels alone had lower predictive
      accuracy. Combining of the correctly identified all of the malignancies. It is
      concluded that preoperative transvaginal ultrasound with color Doppler flow
      mapping is valuable tool in the assessment of adnexal tumors and can be of
      assistance in prediction of ovarian cancer.

PMID- 9289440
TI  - [Thromboembolism prophylaxis in pregnancy and labor].
AB  - Oral anticoagulants are contraindicated during pregnancy, especially during the I
      and III trimester, therefore heparin is recommended instead. We used fraxiparine
      s.c. once daily in prophylactic doses in 6 patients during pregnancy and labor
      (mean time of prophylaxis 6.5 months). Two of them received fraxiparine because
      of mechanical valve prosthesis, four after deep venous thrombosis occurring
      during the first few weeks of pregnancy. The pregnancies were uneventful,
      thromboembolic or haemorrhagic complications during delivery did not occur.
      Newborns were healthy, disturbances of hemostasis were not observed.

PMID- 9289443
TI  - [Evaluation of hormone therapy in women during postmenopause with the help of
      Kliogest].
AB  - Seventeen women were observed during a six-month lasting period of replacement
      hormonotherapy. In all women there appeared decrease in subjective symptoms, as
      well as decrease in the blood level of FSH and LH and increase in the blood level
      of estradiol were observed.

PMID- 9289444
TI  - [Usefulness of counting leukocytes and round cells in determination of bacterial
      infection of semen in infertile men].
AB  - The authors measured efficiency of the determination of bacterial infection from
      the semen of infertile men. They compared the correlation of counts of bacteria
      with white blood cells (peroxidase method) and round cells in ejaculate. Seminal
      white blood cells counts (more than 1 x 10(5)/ml) correlated well with
      bacteriospermia (more than 1000 cells/ml), R = 0.4741, p = 0.0007. Determination
      of round cells in semen has no clinical value in prediction of seminal infection,
      R = 0.0153, p = 0.6022.

PMID- 9289445
TI  - [Chorea gravidarum--case report].
AB  - A case of a 19 years old pregnant girl with chorea gravidarum is described, the
      diagnosis assuming rheumatic background to be the direct cause of the disease.
      Administered were: relanium, penicillin, solu-medrol and encorton with a positive
      therapeutic outcome.

PMID- 9289446
TI  - [Alloimmune neonatal thrombocytopenia caused by serologic incompatibility of HPA
      1a platelet antigen--case report].
AB  - A case of newborn of the 7th pregnancy; 3rd delivery with NAIT is presented. We
      focus on the necessity of performing serological diagnostics of platelet antigens
      and antibodies if in the former neonate the thrombocytopenia of unknown etiology
      was observed or previous pregnancies resulted in natural abortion of unknown
      origin.

PMID- 9289447
TI  - FIGO Committee for the study of ethical aspects of human reproduction. Guidelines
      regarding informed consent. International Federation of Gynecology and
      Obstetrics.

PMID- 9289448
TI  - FIGO committee for the study of ethical aspects of human reproduction. Violence
      against women. International Federation of Gynecology and Obstetrics.

PMID- 9289449
TI  - FIGO committee for the study of ethical aspects of human reproduction. Ethical
      aspects in the management of the severely malformed fetus. International
      Federation of Gynecology and Obstetrics.

PMID- 9289450
TI  - [Mathematic models of fetal maturity based on ultrasonographic monitoring].
AB  - An ability to fetal maturity prediction is particularly important in high risk
      pregnancies. A computer-aided ultrasonographic monitoring of pregnancy enables to
      assess an actual fetal maturity on the base on two or more ultrasound
      measurements. This paper presents a mathematical method of the actual fetal
      maturity evaluation on the base a single ultrasound measurements.

PMID- 9289451
TI  - [Evaluation of fetal condition in pregnancy complicated by hypertension-
      biochemical assessment of amniotic fluid. I. Protein and lipid components and
      kidney maturation].
AB  - Sixty two samples of amniotic fluid were submitted to biochemical investigation
      including 31 samples from women with pregnancy complicated by hypertension
      (studied group with mean blood pressure 165 +/- 15/95 +/- 5 mmHg) and 31 samples
      deriving from healthy pregnant women (control group with mean blood pressure 118
      +/- 10/74 +/- +/- 9 mmHg). In the studied group pregnancy induced hypertension,
      primary hypertension and nephrogenic hypertension scored 58%, 32% and 10% of
      cases respectively. Both investigated and control groups consisted of pregnant
      women with the same gestational age of 37 +/- 2 weeks (34-40 weeks). The
      following parameters of amniotic fluid were measured: 1) total protein, 2)
      albumin, 3) beta-lipoprotein, 4) cholesterol, 5) uric acid, 6) urea, 7)
      creatinine. Micromethods were used. Amniotic fluid deriving from women with
      pregnancy complicated by hypertension showed decreased concentrations of total
      protein, albumin and beta-lipoprotein. In pregnancy complicated by hypertension
      kidneys of the fetuses were estimated to be as mature as in the normal pregnancy
      within the same gestational age.

PMID- 9289452
TI  - [Evaluation of fetal condition in pregnancy complicated by hypertension-
      biochemical assessment of amniotic fluid. II. Enzymes].
AB  - Sixty two samples of amniotic fluid were submitted to biochemical investigation
      including 31 samples from women with pregnancy complicated by hypertension
      (studied group with blood pressure -65 +/- 15/95 +/- 5 mm Hg) and 31 samples
      deriving from healthy pregnant women (control group with mean blood pressure 118
      +/- 10/74 +/- +/- 9 mm Hg). The following parameters of amniotic fluid were
      measured: 1) aminotransferases: alanine AlAT and aspartate AspAT, 2) alkaline
      phosphatase (APt) and its thermostable isoenzyme (APh), 3) ceruloplasmin (Crlp),
      4) alpha-amylase (alpha-Amy). The study showed pregnancy complicated by
      hypertension is related to fetal salivary gland's immaturity presenting decreased
      activity of alpha amylase in amniotic fluid. Amniotic fluids deriving from women
      with pregnancy complicated by hypertension showed normal activities of AlAT,
      AspAT, APt, APh and Crlp.

PMID- 9289455
TI  - [Primary fallopian tube carcinoma. Analysis of 32 cases].
AB  - A retrospective analysis of 32 patients with primary fallopian tube carcinoma
      treated at Center of Oncology in Krakow is presented. In all cases therapy
      consisted of primary total abdominal hysterectomy with bilateral salpingo
      oophorectomy followed by adjunctive radiotherapy. Five year without evidence of
      disease survived 53.1% of the patients. Stage of disease was the only prognostic
      factor: survival at 5 years was 76.9% for stage Io, 55.6% for stage IIo, and 20%
      for stage III.

PMID- 9289454
TI  - [Magnesium and calcium level in blood serum of pregnant women with pregnancy
      threatening miscarriage].
AB  - Concentration of magnesium and calcium was determined in the blood serum of 43
      women with pregnancy threatening miscarriage and 32 ones with normal uterine
      pregnancy in the time interval from 6th to 22nd week. I spite of considerable
      oscillations in magnesium concentration, particularly in the group of threatened
      pregnancies as compared with the normal ones, the differences were not
      significant. Neither were there found any significant differences in calcium
      concentration between the populations tested.

PMID- 9289453
TI  - [Evaluation of fetal condition in pregnancy complicated by hypertension-
      biochemical assessment of amniotic fluid. III. Acid-base balance].
AB  - Sixty two samples of amniotic fluid, collected by ultrasound guided
      amniocentesis, were submitted to biochemical investigation including 31 samples
      from women with pregnancy complicated by hypertension (studied group) and 31
      samples deriving from healthy pregnant women (control group with). The following
      parameters of acid-base balance were measured in amniotic fluids of both groups:
      pH, pCO2, base deficiency, standard HCO3 and total CO2. Corning device type 168
      was used. Distinct metabolic-respiratory acidosis was present in amniotic fluids
      of studied group showing the decrease of a pH, pO2, standard HCO3 values and an
      increase of CO2 values and base deficiency. Authors believe in pregnancy
      complicated by hypertension biochemical environment of intrauterine fetal
      development with regard to acid-base balance is highly unfavourable.

PMID- 9289456
TI  - [Index of fetal maturity].
AB  - A fetal maturity is a typical evolutionary notion. It signifies some level of
      human development and if it concerns a fetus, it means an ability to survive
      outside mothers womb. This paper presents a new practical fetal maturity index (Q
      quotient) which is common for all method of fetal maturity evaluation.

PMID- 9289457
TI  - [Substance abuse and pregnancy: alcohol].
AB  - Alcohol is one of the most widespread substances being abused. In recent years
      the usage of alcohol has increased in most societies. Its abuse concerns also
      pregnant women. In this article the problem of alcohol consumption during
      pregnancy is taken up.

PMID- 9289458
TI  - [Spontaneous uterus eversion in a primipara after delivery repositioned manually
      under fenoterol premedication].
AB  - The complete, spontaneous uterus eversion in 23 years old primipara in the third
      stage of normal labour is described. After detachement of placenta the uterus was
      repositioned manually. To make the procedure easier the drip infusion of
      fenoterol was applied.

PMID- 9289459
TI  - [Coexistence of endometrioid ovarian tumor and squamous cell carcinoma of the
      cervix].
AB  - A case of the coexistence of the endometrioid ovary carcinoma and frank cervical
      carcinoma was shown. The diagnostic procedure, surgery and complementary therapy
      were described. On the basis of the follow-up of the patient it seams that the
      coexistence of these carcinomas neither accelerate the development of disease nor
      make worse the prognosis.

PMID- 9289461
TI  - [Analysis of the questionnaire for prenatal ultrasonography in women delivering
      at the Polish Mother's Memorial Hospital in the year 1995].
AB  - After delivery at the Polish Mother's Memorial Hospital, Lodz Poland (PMMH), 1658
      women were asked to fulfill the questionnaire regarding US studies during their
      pregnancy. At least one US study had 94% (1559) of pregnant women, 6% (99) had
      none. Three-US studies (the optimal number recommended by the authors) had 26%, 2
      US studies had 33%, 1-US studies had 22%. Our data confirm that the series of 3
      US studies during the low risk pregnancy, as it is recommended in most European
      countries needs further promotion and implementation in Poland. In our center, in
      the majority of cases, 4 or more US studies were performed in high risk
      pregnancies.

PMID- 9289460
TI  - [Collagen degradation products in amniotic fluid].
AB  - It was found that amniotic fluid (38-42 Hbd) contains hydroxyproline in
      concentration about 10 micrograms/ml. Gel filtration and dialysis demonstrated
      that most of hydroxyproline exists in a form of low molecular weight products.
      Furthermore, it was found that amniotic fluid contains a protein which eluates
      during gel filtration in void volume of the column. It gives a positive reaction
      for hydroxyproline but the absorption spectrum of such product is not
      characteristic for this amino acid. Furthermore, it is not digested by bacterial
      collagenase. It allows to conclude that amniotic fluid (38-42 Hbd) does not
      contain collagenous proteins. Only low molecular weight degradation products were
      found. Only part of them is susceptible on the action of bacterial collagenase.

PMID- 9289462
TI  - [The effect of total estrogens and lactogen hormone on lipid metabolism in women
      during normal pregnancy].
AB  - Lipids parameters and total oestrogen and HPL levels were estimated in blood
      serum. Investigated group consisted of 45 women with uneventful course of
      pregnancy. All pregnant women were in the gestational age between 29 and 40
      weeks. This is positive correlation increased concentration of total lipids, LDL
      fraction, phospholipids, triglycerids and raising of total oestrogens. High
      concentration of total cholesterol, LDL cholesterol fraction and phospholipids
      were observed at the same time as increased levels of HPL. We suggest that
      multivariative hormonal changes during uncomplicated course of gestation could be
      the cause of modificated lipids profile.

PMID- 9289463
TI  - [Bile acids in blood serum of women during normal pregnancy, early puerperium and
      in the neonate].
AB  - Total bile acids in serum blood samples from 325 subjects were estimated. Study
      group consisted of 50 nonpregnant women, 40-in the I trimester, 50-in the II and
      100-in the III trimester of gestation, 55 patients in the third day of puerperium
      and 30 newborn infants (cord serum). All women were healthy, their age varied
      between 20 and 36 years. Children were mature, born in good condition (Apgar
      score > 8 points). Bile acids concentration were determined using enzymatic
      method with reagent kits by Nycomed Pharme, Norway. In the course of pregnancy
      continuous increase of investigated compounds was observed. The concentration of
      bile acids in puerperium was lower than in the III trimester of pregnancy and
      equal to that determined in cord serum. Authors conclude that during normal,
      uneventful course of gestation symptomless, benign intrahepatic cholestasis
      occurs.

PMID- 9289464
TI  - [Morphometric analysis of the human placenta in physiologic term pregnancy].
AB  - Thirty placentas (after physiological deliveries of full term pregnancies) were
      morphometrically examined. Computer aided analysis of microscopic picture was
      used in those examinations. Measurements of terminal villi and epithelial plates
      were underwent. The efficiency of measuring methods was confirmed in morphometric
      examinations. The area of metabolic transport in placental plates was estimated
      to 1,222 m2. The results of measurements may constitute the basis for further
      examinations on morphology placenta.

PMID- 9289465
TI  - [The effect of ovariectomy in women on metabolism of phenazone].
AB  - The studies were aimed to prove the effect of surgical ovariectomy in women with
      normal estrogen levels on the metabolism of medicaments in the hepatocyte.
      Phenazone, which has lost its significance as a medicament, was used as a model
      substance since it is often used as a preparation in the pharmacokinetic
      investigations. Phenazone levels in sera of women's blood were tested twice. The
      first test was carried out in the women before the operation which included among
      other things a surgical ovariectomy. Before the operation, the women manifested
      normal estrogen levels. The test was repeated 30 days after the operation.
      Phenazone levels were again tested after oral administration of phenazone in the
      dose of 18 mg/kg body mass. Before each test, the women were checked twice for
      the clinical and laboratory parameters of liver functions. Phenazone levels were
      determined seven times in the blood serum at 3- to 6-hour intervals within 24
      hours. The determinations were performed using the Brodie (Brody) method. Average
      phenazone levels in blood sera were given mathematical analysis in the women
      before and after surgical ovarlectomy. The two curves were compared to obtain
      statistically significant differences in most pharmacokinetic parameters. It was
      shown that sudden drop in estrogen levels due to surgical ovariectomy causes a
      diminished constant elimination (K), prolongation of half-life (t0.5), an
      increase in distribution volume (Vd), its reduced derivative (Vd) and increased
      distribution volume calculated from the area under the curve (VdAUC). It points
      to the effect of estrogens on the metabolism of medicaments in the liver and
      indicates a careful dosage of some medicines in chronic use which have a long
      biological half-life in post-menopausal women and in women following surgical
      ovariectomy.

PMID- 9289466
TI  - [Evaluation of SCC antigen in patients with advanced cervix cancer treated with
      radiation].
AB  - The TA-4 antigen was isolated and described in 1977 by Kato and Torigoe. The
      antigen called SCC-squamous cell carcinoma is subfraction TA-4 isolated of liver
      metastases from cervix uteri. The cut-off limits for SCC-antigen is counted as
      1.5-2.5 ng/ml. The level of SCC-antigen was determined in the serum of 41 women
      with advanced cervix uteri cancer-IIIB and IV FIGO stage. The value of SCC
      antigen was evaluated twice: before and after the treatment. The increasing of
      SCC-level was observed in the serum of 80% women. The conclusion are: There was
      the lowering of SCC-antigen value in patients after the irradiation. In cases of
      patients who still had high SCC-antigen level after the treatment and it exceeded
      8 ng/ml., progression of cancer also was found. The progression of cancer after
      the treatment was found in women with pretreatment level of SCC-antigen higher
      than 30 ng/ml.

PMID- 9289467
TI  - [Combined dose distribution in the small pelvis of postsurgical radiotherapy
      patients with cancer of the endometrium].
AB  - X-ray's doses in the pelvis area was published and discussed in this paper. On
      the CT scan base, doses was calculated by the treatment planning system Target 2
      plus. The analysis of dose distribution was performed on 26 patients with the
      postsurgical cancer of endometrium. The treatment was combined teletherapy and
      brachytherapy techniques.

PMID- 9289468
TI  - [Immunology of early pregnancy. I. Immunologically competent cells in the
      endometrium and decidua].
AB  - Changes in the proportion of macrophages, granulocytes and subpopulations of
      lymphocytes in the secretory endometrium and decidua have been reviewed. The
      decidual transformation and principles of the neutralization of an adaptative
      response to embryonic tissues as well as the fetal growth promoting decidual
      factors have been discussed. The immunological response can broadly be divided
      into two types, cell mediated and humoral. Cell-mediated immune responses involve
      the activation of macrophages and the induction of macrophages and the induction
      of cytotoxic CD8+ and CD4+. T cells, whereas humoral immunity is characterized by
      antibody production. These two arma of the immune response are regulated by
      distinct subsets of CD4+ helper T cells, termed Th1 and Th2 cells, which secrete
      different patterns of cytokines. The pregnancy induced possible Th2 prevalence so
      as role of such factors like PGE2, TGF2, 1.25-(OH)2-Vit. D3, IL-2, progesteron,
      estrogens and dehydroepiandrosteron have been reviewed.

PMID- 9289470
TI  - [Pregnancy in the rudimentary horn of the uterus--case report].
AB  - A rare case of pregnancy in rudimentary horn is presented. As the result of
      rupture of the horn in 12th week of pregnancy, the horn had to be resected with
      the fallopian tube. Two years later the patient was pregnant again and delivered
      in time by natural labour.

PMID- 9289469
TI  - [Immunology of early pregnancy. II. Decidua and trophoblast relationship].
AB  - Immunological competent cells and their cytokines exert a potent influence on
      both the placental function and the fetus. The different fetal and placental
      cells and in the same way modify cytokines production by the immunological
      system. The further characteristic of decidual lymphocytes subpopulations and
      their role in the regulation of embryonic development has been presented. The
      interactions between cytokines and growth factors derived from both decidua and
      trophoblast have been reviewed. The role of HLA-G, TLX and expressed cell
      differentiation antigens (complement system suppression) in the early pregnancy
      protection as well as trophoblast invasion inhibition have been discussed. The
      potential role of these factors in the early pregnancy loss has been considered.

PMID- 9289471
TI  - [Polypectomy in the colon--prevention of carcinoma or cosmetic advantage?
      Learning curve of European physicians--approaches for optimization].

PMID- 9289472
TI  - [Polyps and polyposis--limits of endoscopic therapy. Are we currently
      overtreating by removing colorectal polyps?].
AB  - Today, endoscopic polypectomy is the standard procedure for the diagnosis and
      treatment of neoplastic polyps of the colon. There is no longer any doubt that
      the adenoma-(dysplasia)-carcinoma sequence actually holds true. Size,
      configuration and histology identify the risk for colorectal carcinoma, and
      endoscopic treatment can be considered a carcinoma-preventive measure. Even in
      the case of invasive carcinoma developing in a tubular adenoma, endoscopic
      polypectomy with a margin of 2 to 3 mm is believed to suffice unless the
      carcinoma involved is undifferentiated and has invaded blood vessels. In the case
      of polyposis coli, endoscopic polypectomy serves to establish an accurate
      classification of the polyposis, however, mass polypectomy must be rejected. In
      adenomatosis coli colectomy with pouch-anal anastomosis is the treatment of
      choice.

PMID- 9289473
TI  - [Doxycycline-induced ulcerous esophagitis].
AB  - Since 1972, a number of publications, in particular in the Anglo-American
      literature, have reported the occurrence of drug-induced esophagitis. Among the
      causative agents under discussion, tetracyclines and their derivatives play a
      leading role. We now report on a case with the aim of describing the typical
      course and clinical symptoms, diagnosis and treatment of such ulcerative
      esophagitis, and also consider the pathophysiological basis for its development.

PMID- 9289474
TI  - [Female sexuality doesn't stop with aging. Physiological aging processes can
      generally be controlled].

PMID- 9289475
TI  - [Bad fortune for elderly women. Demographic considerations complicate the search
      for new partners].

PMID- 9289476
TI  - [Sexuality in old age homes--a taboo zone. Interview by Beatrice Wagner].

PMID- 9289477
TI  - [Infectiology of the urogenital tract. 4: Quality assurance--antibiotic selection
      in uncomplicated urinary tract infections].

PMID- 9289478
TI  - [General practice 2000--what should be done today?. Interview by Till Uwe Keil].

PMID- 9289479
TI  - The psychoanalyst at the movies.

PMID- 9289480
TI  - [Gaceta Sanitaria 1995-1996: balance and prospects].

PMID- 9289481
TI  - [Transverse study on sex behavior associated with HIV transmission among
      homosexual men in Catalonia].
AB  - In 1993, a cross sectional study was carried out on the sexual behaviour of a
      sample of homosexual men recruited in saunas, sex shops and a gay community
      beased organisation of Catalonia. A total of 551 men with an average age of 34
      years and a high educational level sent in an anonymous questionnaire. In the
      previous 6 months the mean number of male sexual partners was 6 and for
      penetrative partners 3. In the previous month, 94% had had oral sex (22% with
      ejaculation) and 76% anal intercourse (38% without a condom and 21% with
      ejaculation). During sex, 51% used alcohol, 34% nitrite inhalants, 20% hashish
      and 10% cocaine, 61% had had the HIV test, with a self-reported HIV prevalence of
      21%. 86% stated that they knew of one or more people infected by HIV or with
      AIDS. The high percentage of men who had unprotected anal intercourse and the
      high self-reported HIV prevalence highlights the need to increase efforts in AIDS
      prevention and research in this group. Monitoring HIV associated sexual
      behaviours provides valuable indicators of the evolution of the epidemic, useful
      for designing and evaluating preventive interventions.

PMID- 9289482
TI  - [Update on regression: softening relationships].
AB  - A frequently used methodology for the analysis of different kinds of health
      problems is based on regression models: lineal, logistic, etc.; these models
      depend on a set of parameters that must be estimated from the data. However, they
      present the drawback of being very rigid since, occasionally, they impose overly
      strict relations between the variables. Non-parametric regression methods present
      the advantage of not establishing a priori restrictions, allowing the data to
      indicates us the appropriate functional form. In this paper several modern non
      parametric regression methods are presented that in addition to their usefulness
      per se can prone to be of invaluable help in the diagnostic process for
      parametric regression methods. The current availability of the necessary software
      should contribute to their increased use which, in turn, will probably lead to an
      improved understanding of the health problems under study.

PMID- 9289483
TI  - [Estimation of the use of seat belts: an observational study and a telephone
      survey].
AB  - OBJECTIVE: To estimate the prevalence of safety-belt use in a telephone survey
      and an observational survey. PATIENTS AND METHODS: Observational survey. Trained
      interviewers studied 4,067 front-seat occupants, at ten intersections of Madrid,
      according to "National Highway Traffic Safety Administration" guidelines.
      TELEPHONE SURVEY: We selected 433 front seat occupants from the Madrid city
      residential telephone directory. The questionnaire was completed by trained
      interviewers. RESULTS: Prevalence by the observational survey was 58.5%, and was
      significantly higher at interurban intersections (OR = 2.1) than city
      intersections. In the telephone survey, the overall prevalence was 94% at
      interurban area and 64% at city area and it was associated with no history of
      lines and positive opinion of effectiveness of safety belts. CONCLUSIONS: The
      safety belt prevalence observed is low, especially in the urban area. The
      telephone survey overestimates the safety belt use, but contributes with useful
      information for planning strategies.

PMID- 9289484
TI  - [Convergence in health: dream or reality?].
AB  - In the last fifty years the distance between the poorest and the richest
      countries, measured in income per capita, has augmented. Keeping in mind the
      absence of economic convergence, this paper use the life expectancy data compiled
      by the World Bank for 125 countries to examine whether their health levels have
      converged in the period 1960-1992. In order to answer this question we apply the
      concepts of beta and sigma convergence and the evolution of the distribution
      developed in the economic literature. The most relevant results that arise from
      the analysis are that 1) there is convergence in the health levels in the world
      during the period 1960-89, 2) the existence of convergence is not sensible to the
      measure used but it is to the variable used to proxy the health level, 3) the
      speed of convergence fell down from the eighties, and 4) the African countries
      reduced the distance from their health level to the levels of the rest of the
      world but, within Africa, the differences increased along 1960-92. These
      evidences suggest a nonlinear relation between health and income per capita.

PMID- 9289485
TI  - [Incidence of bronchopulmonary carcinoma in the Province of Caceres (1986-1995)].

PMID- 9289486
TI  - [Prison environment, HIV/AIDS and health promotion].

PMID- 9289487
TI  - [Health promotion in relation to HIV in the prison environment].

PMID- 9289488
TI  - [Modeling of daily mortality in the Autonomous Community of Madrid (1986-1991)].
AB  - OBJECTIVE: To describe, estimate and model trends and seasonal variations in
      daily mortality in the Comunidad of Madrid, Spain. METHODS: Overall mortality
      rate, as well as gender, age and cause-specific mortality rates between january
      1, 1986 and december 31, 1991 were analyzed. A cyclic pattern was detected using
      fast Fourier transform. Mortality was modelled using ARIMA stochastic models and
      Poisson regression models. RESULTS: Spectral analysis detected two statistically
      significant periodic components (winter-summer). Winter peak was related mainly
      to an excess in cardiovascular diseases in women aged 65 and over, as well as
      with cardiovascular, respiratory and digestive diseases in men aged 45 and over.
      The summer peak was related with women, aged 65 and over with cerebrovascular
      diseases as the cause of death. CONCLUSIONS: The two cycles detected support the
      hypothesis of an association between mortality and environmental factors.

PMID- 9289489
TI  - Oxidative decay of DNA.

PMID- 9289490
TI  - Novel Ca2+-binding protein (CAPS) related to UNC-31 required for Ca2+-activated
      exocytosis.
AB  - Exocytotic secretion in neuroendocrine cells is activated by cytoplasmic Ca2+
      increases. Late post-docking events in dense core vesicle exocytosis in permeable
      PC12 cells require cytosolic factors for sequential ATP-dependent priming and
      Ca2+-dependent triggering steps. The cytosolic proteins phosphatidylinositol
      transfer protein and phosphatidylinositol (4)-phosphate 5-kinase, as well as
      membrane-bound N-ethylmaleimide-sensitive factor, are required for the ATP
      dependent priming step. Following priming, the Ca2+-dependent triggering of
      vesicle fusion requires an additional cytosolic factor, CAPS, which was purified
      as a 145-kDa protein. To clarify late Ca2+-dependent events in vesicle fusion,
      the sequence of rat CAPS cDNA was determined and found to encode a novel protein
      that is the vertebrate homologue of the Caenorhabditis elegans UNC-31 protein
      shown genetically to be required for neurosecretion. Recombinant CAPS substituted
      for cytosol in the Ca2+ triggering step in permeable PC12 cells and exhibited
      moderate affinity (Kd = 270 microM) Ca2+ binding (2 mol Ca2+/mol CAPS dimer),
      consistent with a role at a Ca2+-regulated step in exocytosis.

PMID- 9289491
TI  - CASH, a novel caspase homologue with death effector domains.
AB  - CASP-8 and CASP-10, members of a cysteine protease family that participates in
      apoptosis, interact with MORT1/FADD, an adapter protein in the CD120a (p55 tumor
      necrosis factor receptor), and CD95 (Fas/Apo-1) death-inducing signaling
      pathways, through a shared N-terminal sequence motif, the death effector domain.
      We report cloning of two splice variants of a novel protein, CASH, that contain
      two N-terminal death effector domains and can bind through them to each other, to
      MORT1/FADD, to CASP-8, and to CASP-10. The unique C-terminal part of the longer
      variant shows marked sequence homology to the caspase protease region yet lacks
      several of the conserved caspase active site residues, suggesting that it is
      devoid of cysteine protease activity. Overexpression of the short CASH splice
      variant strongly inhibited cytotoxicity induction by CD120a and CD95. Expression
      of the longer variant, while inhibiting cytotoxicity in HeLa cells, had a marked
      cytocidal effect in 293 cells that could be shown to involve its protease
      homology region. The findings suggest that CASH acts as an attenuator and/or
      initiator in CD95 and CD120a signaling for cell death.

PMID- 9289492
TI  - Research radionuclide availability in North America: part 2.

PMID- 9289493
TI  - The Canadian Rheumatology Association Meeting. Mont Tremblant, Quebec, February
      26-March 1, 1997. Abstracts.

PMID- 9289494
TI  - [Percutaneous bile drainage in neoplastic obstructive pathology of the biliary
      tract. Experience of the Hotel-Dieu of France in 100 drainages].
AB  - Between 1981 and 1994, a 100 biliary drainages were introduced transhepatically
      in 71 patients with malignant biliary disease. Eighty-six endoprosthesis were
      inserted, 6 internal-external drainages and 8 external drainages. Our success
      rate in catheterization of the stenosis was 97%. The early complication rate was
      17% (12/71) most often due to hemorrhage (n = 3), infection (n = 4), duodenal
      perforation (n = 1), biliary leak (n = 2) and death by septic shock (n = 2).
      Twenty-nine patients with 39 endoprosthesis had a long-term follow-up. The most
      common late complication observed was occlusion (15/39, 37%) and migration (1/39,
      2.5%). Specific treatment of complications was carried out in 10 of the 29
      patients (35%). It is concluded that patients with inoperable malignant
      obstruction of the bile ducts should be offered an indwelling endoprosthesis
      whatever their prognosis; an occluded stent can be removed or at least bypassed
      in nearly all patients, thereby maintaining palliation of symptoms.

PMID- 9289495
TI  - [Coronary surgery in patients 70 years and older. Report of 70 cases].
AB  - Between January 1993 and January 1995, seventy patients over 70 years of age
      underwent coronary artery revascularization and were retrospectively reviewed.
      The anesthetic protocole, the surgical technique and the intraoperative
      myocardial protection were similar for all patients. Fourteen patients (19.8%)
      suffered major postoperative complications: stroke (3 cases), myocardial
      infarction (5 cases), left ventricular failure with intraaortic counter-pulsation
      (2 cases), gastrointestinal hemorrhage (2 cases), respiratory failure (2 cases).
      Thirty patients (42.6%) had minor complications with no impact on survival or
      hospital stay. Hospital mortality was 7.1% (5 patients) and was caused by left
      ventricular failure (2 cases), stroke (1 case), gastrointestinal hemorrhage (1
      case), respiratory failure (1 case). Mortality was found to be correlated with
      preoperative renal failure, peripheral vascular disease and concomitant carotid
      endarterectomy. Patients remained in the cardiac surgery unit for 60 hours. The
      mean length of hospital stay was 8.2 days. Follow-up from 1 to 24 months revealed
      NYHA angina class I-II in 85% of the patients. These results are similar to other
      studies. We conclude that coronary artery revascularization in the elderly yields
      good results, with fair mortality and morbidity rates.

PMID- 9289496
TI  - [Screening of Streptococcus agalactiae (group B) in the perinatal period].
AB  - OBJECTIVE: To determine the carriage rate of Streptococcus agalactiae in a group
      of pregnant women and evaluate its role in a neonatal infections. DESIGN:
      Prospective study between December 1992 and May 1993. SETTING: University
      hospital. PARTICIPANTS: 166 patients aged 17 to 41 years (m = 28 yrs) with a
      gestational age of 32 to 42 wks (m = 39.99 +/- 1.73) were admitted to the
      delivery suite. All patients had a vaginal swab on admission before any lavage.
      RESULTS: The recovery rate of Streptococcus agalactiae (group B) was found to be
      7.8% (13/166) in our population. Twelve of the thirteen newborn to colonized
      mothers (92%) were term newborn as compared to 141 of 153 (92.1%) newborn to non
      colonized mothers (p = 0.72). Three of thirteen (23%) colonized mothers had
      premature rupture of membranes and 23% (3/13) had prolonged labor > 12 h as
      compared to of 38 (25.1%) and 8 (5.1%) non-colonized mothers (respectively p =
      0.58; NS; p = 0.035). No intra-partum fever was reported. All neonates born to
      colonized mothers had a birth weight > 2,800 g, an average Apgar score of 8.6
      while neonates of non-colonized women had a weight > 2,800 g in 89.4% of cases
      and an average Apgar of 8.8 (p = 0.9). Two (15.4%) newborn infants born to
      colonized mothers had an early neonatal infection: one had a pneumonia and had a
      favorable outcome, the other one developed sepsis and meningitis and died on day
      3. CONCLUSION: Despite the low rate of Streptococcus agalactiae (group B)
      colonization (found in our population), regular identification of the organism is
      recommended because of the high risk of neonatal infection with a high mortality.
      Further studies on a larger group are needed to confirm such an approach.

PMID- 9289497
TI  - [Accidents in children. Retrospective epidemiological study of 1671 cases
      collected at the Hotel-Dieu of Beirut].
AB  - Injuries are the first cause of death in children after the neonatal age; their
      prevention is still critical in Lebanon. At Hotel-Dieu de France Hospital, 1671
      children aged less than 18 years have had their files reviewed in the emergency
      department. Minor traumas represent less than half the cases. Though most of the
      injuries were light, in 5% of cases primary care was necessary, and 11% were
      admitted (10% in the Pediatric Intensive Care Unit); 0.5% of the children died
      upon arrival. Moreover, 15% of our Pediatric Intensive Care Unit population are
      admitted for accidents. Boys are more frequently affected (69%); toddlers, small
      children and adolescents are risky populations. After minor traumas, the most
      frequent accidents are: falls (21.3%), traffic road accidents (8.9%), poisoning
      (5.7%) and burns (5%). Firearms injuries seem rare (2.8%) but are, in this study,
      the first cause of mortality. Foreign body inhalation are very rare (< 1%) but
      are a significant source of morbidity. This analysis is compared to published
      data, and allows accurate and general recommendations for injuries prevention in
      children.

PMID- 9289498
TI  - [Validation of choice of experts for the spondylarthropathy study in Lebanon].
AB  - A study of the spondylarthropathies, their recent diagnostic criteria and the
      prevalence of HLA B27 in these affections in Lebanon will soon be started.
      Experts will have to include patients, prospectively, and to classify them as
      having or not a spondylarthropathy, according solely to their clinical judgement.
      The decision of the expert is of major importance in including patients in the
      study. We performed a clinical evaluation of inter-observer variability to select
      experts according to a significant concordance in the clinical diagnosis of
      different rheumatic diseases, especially spondylarthropathies. Results of the
      evaluation are presented and discussed.

PMID- 9289500
TI  - [Congenital diverticula of the ureter].
AB  - We report a case of congenital diverticulum of the ureter diagnosed during the
      neonatal period in a female patient associated with a contralateral multicystic
      kidney. The prenatal ultrasound has suspected the presence of hydronephrosis and
      the final diagnosis was made after birth by the intravenous pyelography and
      retrograde uretro-pyelography. A simple resection with termino-terminal
      anastomosis was made with uneventful postoperative course.

PMID- 9289499
TI  - [Thermocoagulation in the treatment of facial neuralgia. Preliminary results in
      22 cases].
AB  - Twenty-two patients suffering from trigeminal neuralgia were treated by
      thermocoagulation from June 92 to June 94 at Hotel-Dieu de France Hospital.
      Epidemiological, clinical, para-clinical elements and the therapeutic approach
      were studied. The results after a median follow-up of one year were satisfactory
      in twenty patients (90.9%) who became asymptomatic. No major complication was
      noticed. Two recurrences occurred however, one responded to another thermolesion.
      We propose and discuss this technic for the treatment of the trigeminal
      neuralgia.

PMID- 9289501
TI  - [Generalized amyloidosis associated with Hashimoto's thyroiditis and
      hypothyroidism].
AB  - Involvement of the thyroid gland in systemic amyloidosis is known since 1855,
      most frequently histologic than clinical. We report here a case of systemic
      amyloidosis associated with myxedema and Hashimoto's thyroiditis which has been
      rarely reported in the literature, and may represent a new example of auto-immune
      diseases associated with systemic amyloidosis.

PMID- 9289502
TI  - [A rare cause of diplopia: a sinus cavernous dural fistula. A case report].
AB  - Dural fistulas of the cavernous sinus represent a relatively unknown etiology for
      diplopia. The authors report on a case where combination of MR and transcranial
      Doppler (especially transocular) helped in diagnostic and therapeutic approach.
      They propose a new algorithm for the management of diplopia.

PMID- 9289503
TI  - [Parathyroidectomy under local anesthesia. First two cases in Lebanon and review
      of the literature].
AB  - The routine use of automated techniques to measure serum calcium levels have made
      disease states of the parathyroid gland a common endocrinologic problem. Because
      of the low sensitivity and specificity of early radiologic techniques to identify
      enlarged parathyroid glands, and because skilled endocrine surgeons report
      success rates of > 95% in identifying abnormal parathyroid glands, historically
      most parathyroid glands surgery consisted in a large cervicotomy under general
      anesthesia without preoperative localization. However, the development of
      sophisticated imaging techniques has now made it possible to identify the
      abnormal gland in a significant number of patients, leading some surgeons to
      choose unilateral neck exploration under local anesthesia for primary
      hyperparathyroidism. The success of the procedure is ascertained by measuring PTH
      peroperatively. We report the first two Lebanese patients, presenting with a
      solitary parathyroid adenoma, who underwent this easy, safe and cost-effective
      surgical technique.

PMID- 9289504
TI  - [Arabic medicine. An unveiled art].

PMID- 9289505
TI  - [Breast feeding practice in a region of Beirut].
AB  - The practice of breast-feeding was reviewed in an inquiry carried on by the
      nursing students in Beirut and suburbs. 170 mothers answered the questionary
      concerning their experience in feeding their 170 babies as well as their previous
      263 children of whom 249 were breast-fed. 31.17% of these mothers were breast
      feeding for the first time. 11% of the newborns were fed in the first hour of
      life. 29% of the newborns received breast milk as the first food. Breast milk
      remained exclusive for the first month of life in 37.54% of these newborns.
      Breast-feeding mothers changed their feeding habit in half of the cases. They
      increased the quantity but the quality of nutriments was still deficient. This
      misunderstanding of breast-feeding is due primarily to the insufficiently
      informed mothers and to the inadequate habits of nursery. It is important to
      ameliorate the quality of information for the breast-feeding mothers and their
      household for the success of any policy encouraging breast-feeding in Lebanon.

PMID- 9289507
TI  - [Effect of antigenemia on diagnosis and determination of the result of therapy of
      cytomegalovirus infection in formerly healthy adults].

PMID- 9289506
TI  - [Thyroid-stimulating hormone hypophyseal adenoma. A case report].
AB  - TSH pituitary adenomas represent less than 1% of operated pituitary adenomas.
      More then 200 cases have been described till now and more patients are now
      identified since the widespread of ultrasensitive TSH assay which can detect
      paradoxical situations of elevated serum thyroxine levels with detectable TSH
      levels. Differential diagnosis must be done with pituitary resistance to thyroid
      hormones, disorder in which there is a state of "TSH mediated hyperthyroidism".
      Transsphenoidal surgery remains the treatment of choice of TSH secreting adenoma.
      A medical treatment with octreotide can improve biological findings and induce
      tumor shrinking. We report in this paper a TSH pituitary adenoma in a young girl
      of 15 years old.

PMID- 9289509
TI  - [Superior vena cava replacement].

PMID- 9289508
TI  - [Superior vena cava replacement].

PMID- 9289510
TI  - Purine and pyrimidine disorders, the porphyrias, homocysteine metabolism,
      trinucleotide repeat disorders. Proceedings of the 34th annual symposium of the
      Society for the Study of Inborn Errors of Metabolism. Cardiff, 1996.

PMID- 9289511
TI  - [Molecular genetics of non insulin dependent diabetes mellitus].

PMID- 9289512
TI  - [It's time to join efforts in favor of the accreditation in infectious diseases].

PMID- 9289513
TI  - [It's time to join efforts in favor of the accreditation in infectious diseases].

PMID- 9289514
TI  - [Diseases in mountain expeditions].

PMID- 9289515
TI  - [Drugs and biomedical journals: better information, more precision].

PMID- 9289516
TI  - [Desperation due to an excess of waiting].

PMID- 9289517
TI  - [Internists and county hospitals].

PMID- 9289518
TI  - [Estimation of potential impact of ambulatory surgery in Catalonia].
AB  - BACKGROUND: In recent years, ambulatory surgery has received much attention in
      Catalonia, Spain, because of its potential to reduce unnecessary bed utilization.
      To estimate the number of potentially ambulatory procedures could be useful for
      planning and contracting health care services and could give an idea of its
      potential impact in the existing health care system. METHODS: The number of
      hospital discharges in Catalonia (1993) for 34 groups of procedures suitable for
      ambulatory surgery were obtained from the computerised uniform hospital discharge
      system. The percentage of procedures that could be carried out as day cases
      published in three delphi studies were applied to the number of hospital
      discharges to estimate a target number of ambulatory procedures. The number of
      hospital bed days that could be saved was calculated multiplying the estimated
      number of ambulatory procedures by the actual average length to stay for each
      procedure. Finally, Delphi substitution percentages were compared to those
      reported by a Catalan hospital with an ambulatory surgery unit. RESULTS: The
      estimated annual number of ambulatory procedures ranges from 37,453 to 44,752
      (6.5 to 7.7% of the annual hospital discharges) and the estimated hospital day
      from 159,773 to 193,709 (3.3 to 4.0% of all hospital bed days). Among the
      procedures with the highest potential in ambulatory surgery there are: cataract
      surgery, inguinal hernia repair, uterine dilatation and curettage, and
      arthroscope. Most of the reported hospital substitution indexes are positioned
      between the highest and the lowest delphi indexes. CONCLUSIONS: A significant
      percentage of the procedures currently carried out on an inpatient basis could be
      performed in ambulatory arrangements. The hospital reported percentages of
      substitution suggest the feasibility of achieving the estimated number of
      ambulatory procedures. In the Catalan public health sector, ambulatory surgery
      has shown an increasing trend towards the estimated number of ambulatory
      procedures.

PMID- 9289519
TI  - [Hematologic deficiencies in patients with recurrent oral aphthae].
AB  - BACKGROUND: The prevalence of iron, folic acid and vitamin B12 deficiencies and
      their role in the development of recurrent oral ulcerations is not well known.
      The aim of this study was to determine the prevalence of these deficiencies in
      our patients. PATIENTS AND METHODS: Iron, folic acid and vitamin B12 levels were
      studied in 80 patients with recurrent oral ulcerations (ROU) and the results were
      compared with a control group of 29 patients with different oral diseases.
      RESULTS: In the recurrent oral ulcers patients, deficiencies were detected in
      21/80 patients (26.2%). In 18 cases they were pure: iron (4), folic acid (10) and
      vitamin B12 (4). In 3 patients, combined deficiencies were detected, being
      secondary to pernicious anaemia in two patients. In the control group,
      deficiencies were observed in 4/29 cases (13.7%). In three cases they were
      isolated (one case suffered from ferropenic anaemia and two patients of
      pernicious anaemia). CONCLUSIONS: Patients with recurrent oral ulcerations have
      more frequently iron, folic acid and vitamin B12 deficiencies than those with
      other diseases of oral mucosa. However, there were not significant differences
      when the frequency of deficiency of each one of such elements were taken into
      account separately.

PMID- 9289520
TI  - [Consumption of sweets and snacks by a population of school children in the
      Autonomous Community of Madrid. The CAENPE Group].
AB  - BACKGROUND: In our society advertising compaigns promote consumption of
      superfluous foods, such as sweets and snacks, displacing the intake of other
      basic nutrients. The aim of this study is to assess the intake of these foods by
      children, their relative contribution to overall macronutrient intake and their
      effects on health. SUBJECTS AND METHODS: A dietary assessment was performed on a
      representative sample of scholar children from the Autonomous Community of
      Madrid. It reflects food consumption for a 4-days period (3 week-days and 1
      weekend day) in 2,698 boys and girls aged 6 to 15 years. The intake is expressed
      as grams per 1,000 kcal to standardize nutrient consumption in boys and girls.
      Lipid profile and several markers of nutritional status are also determined.
      RESULTS: The consumption of sweets and snacks items per 1,000 kcal is higher in
      boys than in girls (35.8 +/- 20.0 and 34.2 +/- 19.6 g/1,000 kcal, respectively; p
      = 0.01) and increases during adolescence (12 and 13 years) in both sexes. Sweets
      and snacks provide 16.1% of dietary total caloric intake, 7.1% of saturated fatty
      acids, 10.7% of monounsaturated fatty acids, 10.4% of polyunsaturated fatty acids
      and 11.3% of cholesterol. Children of ages 6, 7, 8 and 9 years with high
      calculated LDL-cholesterol levels (> or = 120 mg/dl) consume significative higher
      amounts of sweet foods than children with low calculated LDL-cholesterol levels
      (< or = 90 mg/dl). CONCLUSIONS: Children from the Autonomous Community of Madrid,
      Spain consume excessive sweets, which could be responsible for a higher
      prevalence of diseases related to this intake, such as caries, obesity and
      obesity-related associate diseases.

PMID- 9289521
TI  - [Major ambulatory surgery and short-stay surgery. Expectations, current reality
      and possibilities].

PMID- 9289522
TI  - [Aphthae].

PMID- 9289523
TI  - [Tacrolimus (FK506): clinical, pharmacological and analytical aspects].

PMID- 9289524
TI  - [Multicenter study on the efficacy of advice for the prevention of alcoholism in
      primary health care].
AB  - BACKGROUND: The aim of this study was to analyse and to verify the efficacy of
      systematic advice for alcoholism prevention, assessing the reduction of the
      number in risk drinkers. PATIENTS AND METHODS: A multicenter randomized
      controlled clinical trial was designed, to perform in general practitioner
      setting, on a sample of risk drinkers (alcohol intake > 280 g weekly, without
      dependence) sent by random in intervention group (systematic brief advice with
      support material and a five visit program during a year) and control group (once
      brief advice and a control in 1 year). The procedure to incorporate in both
      groups included physical exam, a blood test and the MALT questionnaire. A
      descriptive and analytic study on included variables was realised, assessing the
      percentage of drinkers who reduced alcohol intake below risk limit at the end of
      a year follow up, as well as the reduction intake in each group. RESULTS: Of the
      139 included males, 75 were in the intervention group and 64 in the control
      group. The percentage of patients not excluded by MALT > 10, and/or liver
      disease, that finished the 1 year follow up, was 46%, being the sample average
      age of 43 +/- 11.8. Patients included in both groups were initially comparable.
      At the end of a year follow up there were statistically significant differences
      in: percentage of risk drinkers who decreased alcohol intake below 280 g weekly
      (82% intervention group; 47% control group); percentage of reduction in GPT, GGT,
      triglycerides, systolic blood pressure and the MALT questionnaire. CONCLUSIONS:
      The efficacy of isolated advice of general practitioner was proved to achieve the
      alcohol intake reduction below the risk limit accepted in male risk drinkers
      without alcohol dependence. The systematic follow up during a year significantly
      improves the results achieved with the isolated advice.

PMID- 9289525
TI  - [Smoking prevalence trends in Catalonia, Spain, 1982-1994].
AB  - BACKGROUND: Smoking prevalence trends from 1982 to 1994 of adult population in
      Catalonia (Spain) are described. SUBJECTS AND METHODS: Four population surveys
      have been carried out periodically using the same questionnaires and definitions
      for smoking status. Surveys in 1982, 1986 and 1990 have been implemented taking
      samples of Catalonia population through a multistage sampling with random
      stratified selection by province and habitat. Individuals were chosen through a
      random route process. In 1994, a survey with a complex probabilistic sample
      design with 8 geographical areas (health regions) and 2 basic units (towns and
      individuals) was implemented. RESULTS: Among the 15-64 years old adults, a
      decrease of 6.9% in smoking prevalence has been observed. The initial prevalence
      in 1982 was 37.9% (CI 95%: 35.4; 40.3); in 1994 this prevalence was 35.3% (CI
      95%: 34.4; 36.2). In 1994, the prevalence of current smokers in population over
      14 years old was 30.6% (CI 95%: 29.8; 31.4). We have observed a significant
      decrease in smoking prevalence in all age groups among male population (-20.6%
      for the 12-year period) whereas prevalence has increased among female (+28.0%)
      mainly among those between 25 and 54 years old. The main percentual decrease in
      smoking prevalence has been observed among young people aged 15-24 years old for
      both genders. The proportion of former smokers has remained stable (11.4% in
      1982, 12.9% in 1994) during the period studied. The proportion of former smokers
      increases with age among man over 25 years. CONCLUSIONS: Smoking habit is still
      very prevalent in Catalonia, even higher than in other Western European
      countries. In spite of the increase among women, the significant dectines of
      smoking prevalence among men and youngsters (of both genders) could represent
      encouraging findings in order to pursue the efforts aimed at reducing the morbi
      mortality burden of smoking in our society.

PMID- 9289527
TI  - [Silicone and disease: myth or reality?].

PMID- 9289528
TI  - [Advice by the family physician and healthy life style].

PMID- 9289526
TI  - [Efficacy and safety of nabumetone in the treatment of knee osteoarthritis: a
      comparative clinical trial versus aceclofenac. Study Group of Nabumetone for
      Osteoarthritis of the Knee].
AB  - BACKGROUND: Non-steroidal antiinflammatory drugs are extensively prescribed for
      the symptomatic treatment of osteoarthritis (OA). This study compared the
      efficacy and safety of nabumetone with aceclofenac in patients with active knee
      osteoarthritis. PATIENTS AND METHODS: Phase IV, multicentre, prospective, open
      label, parallel-group, randomized, three-month treatment, clinical trial, of
      nabumetone (1-2 g once a day) vs aceclofenac (100 mg two times each day). The
      main efficacy variable was intensity of pain, evaluated on a Visual Analogic
      Scale (VAS). In addition: Gonarthrosis Severity Index (GSI)-baseline score > 5
      and < 17-, patient and physician Global Assessment of OA Activity, patient and
      physician Global Assessment of OA progression were assessed. Adverse events
      incidence and severity were assessed. Three study visits were made on a monthly
      basis. The main statistical analysis was by intention to treat (ITT). RESULTS: In
      12 centres 274 patients were recruited (137/group), aged 62.5 +/- 8.4 years, of
      whom 189 completed the trial (97 nabumetone and 92 aceclofenac). 90% were female,
      and 83% of the patients had both knees affected. In both groups the intensity of
      pain at month 3 improved significantly (p < 0.001) with respect to baseline: VAS
      of the nabumetone group: 6.1 +/- 1.9 to 4.3 +/- 2.8 cm; VAS of the aceclofenac
      group: 6.1 +/- 1.9 to 4.4 +/- 2.7 cm. There were no significant differences in
      any of the intergroup comparisons made. 15 nabumetone-treated and 23 aceclofenac
      treated patients withdrew from the study due to moderate to severe adverse
      events. Gastrointestinal adverse events were the reason for withdrawal in 7
      nabumetone and 14 aceclofenac-treated patients. CONCLUSIONS: The efficacy and
      safety of nabumetone are similar to those of aceclofenac in the treatment of knee
      osteoarthritis.

PMID- 9289529
TI  - [Family and social aspects in dementia].

PMID- 9289531
TI  - [Splenectomy as the treatment in a case of recurrent thrombotic thrombocytopenic
      purpura in a patient with HIV infection].

PMID- 9289530
TI  - [Dyspnea and cough in a 58-year-old male].

PMID- 9289532
TI  - [Resolution of a disseminated infection by Fusarium solani in a patient with
      acute promyelocytic leukemia and granulocytopenia secondary to chemotherapy by
      the combined use of G-CSF and liposomal amphotericin B].

PMID- 9289533
TI  - [Spontaneous hemoperitoneum due to rupture of a regenerating nodule as primary
      manifestation of hepatic cirrhosis].

PMID- 9289534
TI  - [Bacteremia by Alcaligenes xylosoxidans: report of a case].

PMID- 9289535
TI  - [The false illusion of medicinal herbs].

PMID- 9289536
TI  - [Treatment with adenosine for supraventricular paroxysmal tachycardia during
      pregnancy].

PMID- 9289537
TI  - [Familial combined hyperlipidemia: detection and characterisation of the
      hyperlipidemic profile among children and adolescents].
AB  - BACKGROUND: Familial combined hyperlipidemia is the commonest genetic form of
      hyperlipidemia among survivors of myocardial infarction and, therefore, its early
      detection is crucial for the prevention of coronary artery disease. The aim of
      the study was to establish the prevalence of hyperlipidemia in the offspring of
      affected families and to characterize their lipid, lipoprotein and apolipoprotein
      profile. PATIENT AND METHODS: Forty five subjects below the age of 19 were
      studied from which 30 were from affected families and 15 from healthy control
      families. Cholesterol and triglycerides in plasma, VLDL, IDL, LDL and HDL as well
      as apolipoproteins AI, B, C-II and C-III were measured. RESULTS: Hyperlipidemia
      was detected in 13 children (43%) from affected families. They also presented
      significantly elevated concentrations of cholesterol in plasma (p < 0.0001), LDL
      (p < 0.0001) and HDL (p < 0.05); triglycerides in plasma (p < 0.007), VLDL (p <
      0.05) and LDL (p < 0.008), together with significantly increased concentrations
      of apolipoproteins AI (p < 0.02), B (p < 0.0004), C-II (p < 0.0005) and C-III (p
      < 0.03). No changes were observed in the IDL fraction. CONCLUSIONS: There is an
      elevated prevalence of hyperlipidemia among the offspring of patients with
      familial combined hyperlipidemia. On the contrary to that observed in adults, no
      alterations of the IDL fraction are present among affected children.

PMID- 9289538
TI  - [Bacteremia in the elderly. Clinical features and prognostic factors].
AB  - BACKGROUND: The analysis of the most relevant characteristics and prognostic
      factors in elderly patients with bacteremia. PATIENTS AND METHODS: For the period
      1989-1993 a prospective study of all significant bacteremias in adult patients
      admitted to a General Hospital was performed. Patients were visited until their
      death or during at least 50 days. The most relevant findings in elderly patients
      (over 65 years old) are described. Overall survival probabilities were obtained
      by Kaplan-Merner analysis. Cox proportional models were used to examine hazards
      of dying. RESULTS: Of the 1,128 bacteremias studied, 603 (53.9%) were in elderly
      patients. In this group, the increasing age was related with higher frequency of
      urinary (p = 0.02) and biliary (p = 0.001) sources of infection and lower
      frequency of underlying neoplasia (p = 0.06), immunosuppression (p = 0.0000) and
      development of septic shock (p = 0.02). These differences are higher in patients
      over 85. Among older patients the survival probability in the day 21 after
      diagnosis was 0.71 (95% CI 0.66-0.74), significantly lower to the probability in
      younger patients (p = 0.0001). In the elderly patients, the worse prognestic was
      associated to shock (RR = 8; 95% CI 5.8-11), indeterminated source of infection
      (RR = 3.6; 95% CI 2.2-5.8), underlying neoplasia (RR = 1.7; 95% CI 1.3-2.4),
      neutropania (RR = 1.5; 95% CI 1.1-2.1) nosocomial acquisition (RR = 1.3; 95% CI
      1.0-3.1) and inappropriate treatment (RR = 1.2; 95% CI 1.0-3.2), but age was not
      an independent contributor. CONCLUSIONS: We found differences between the
      clinical characteristics and the prognosis of bactermia in elderly and younger
      patients. Among elder patients, those over 85 years old constitute a particular
      group with well defined characteristics.

PMID- 9289539
TI  - [The female sex is an independent prognostic factor for mortality in the acute
      phase of myocardial infarction].
AB  - BACKGROUND: To assess the effect of female gender on mortality after acute
      myocardial infarction (AMI), we studied a cohort of 876 consecutive patients,
      being women 253 of them (28.8%), admitted to the intensive Care Unit (ICU)
      because of a first AMI, from September 1992 to October 1995. PATIENTS AND
      METHODS: We compared the clinical characteristics, the complications and the
      treatment in both sexes. We estimated the relative risk using logistic
      regression, being the sex, the independent variable and dependent variables age,
      history of hypertension and diabetes, AMI location and thrombolytic treatment.
      RESULTS: The age was higher and the history of hypertension and diabetes more
      frequent. The AMI location was less often inferior. Women received fibrinolytic
      treatment less frequently in women than in men. The mortality in the ICU was
      higher in the women (29.2 vs. 13.5% in the men) and, after adjusting for the
      previous factors the relative risk was 1.51 (95% confidence internal of 1.01
      2.26). CONCLUSIONS: In the population studied, the female gender is an
      independent risk factor for early mortality in the AMI.

PMID- 9289540
TI  - [Familial combined hyperlipidemia].

PMID- 9289541
TI  - [Epidemics and society: from leprosy to AIDS].

PMID- 9289542
TI  - [Autologous hemopoietic progenitor cell transplantation in chronic myelogenous
      leukemia].

PMID- 9289543
TI  - [Metabolic host-tumor relationships during perinatal phase].

PMID- 9289544
TI  - [Inappropriate hospital admission and stay according to the Appropriateness
      Evaluation Protocol. Study of point prevalence in a geriatric department].

PMID- 9289545
TI  - [Is a second dose of the triple viral vaccine necessary?].

PMID- 9289546
TI  - [The videodisc for medical training. Should it be massively introduced in
      Spain?].

PMID- 9289547
TI  - [Echographic diagnosis of inferior pancreatoduodenal artery aneurysm].

PMID- 9289548
TI  - [Intraoperative serum parathyroid hormone measurement in the surgical treatment
      of hyperparathyroidism].
AB  - BACKGROUND: PTH(1-84) short half life permits us to monitor parathyroidectomy
      efficacy, confirming complete resection after unilateral surgical approach in
      some cases of primary hyperparathyroidism. Nevertheless, this utility has been
      tested in controlled clinical trials and there is no agreement regarding the
      extraction of samples, their processing and interpretation of results. PATIENTS
      AND METHODS: In 18 consecutive patients operated on for primary or secondary
      hyperparathyroidism, serum PTH(1-84) concentrations were assessed at different
      times before, during and after partial (in 11 patients with multiglandular
      illness) and total resections. RESULTS: Initial PTH(1-84) concentrations very
      largely in different pre-resection samples, and these variations significantly
      affect post-resection percentage reduction. Plasmatic clearance of PTH(1-84)
      after incomplete resection follows a decreasing exponential curve towards new
      equilibrium concentrations. The difference is significant comparing with
      concentrations following complete resection only 5 minutes after, but the 95%
      intervals with a confidence level of 90% of confidence are exclusive only for
      determinations after 120 minutes. CONCLUSIONS: The decrement of serum PTH(1-84)
      concentrations to 20% of the preresection levels 120 minutes after an
      adenomectomy confirms the complete removal of all pathologic parathyroid tissue.
      A less sharp decrement must be investigated and may justify an early surgical
      revision.

PMID- 9289549
TI  - [Hospital at home and conventional hospitalization. An economic evaluation].
AB  - BACKGROUND: To carry out an economic evaluation of hospital at home (HH) vs.
      conventional hospitalization (CH) from the hospital cost perspective. METHODS: A
      minimization cost analysis were performed in 2 groups of patients (HH: 148
      patients, 1,776 days of care; CH: 148 patients, 1,113 days) with similar
      characteristics. We used cost per hospital episode (only for the comparable
      period in HH and HC) and cost per day as outcome measures. The costs of health
      care professionals, pharmacy, sanitary material, diagnostic and therapeutic tests
      and transport were directly estimated for each patient. Other costs were
      indirectly assigned from the hospital accountability information system. RESULTS:
      The average episode cost at home was 172,043 ptas. (about $1,300) less compared
      to the conventional hospitalization. Cost per diem for HH was 25,565 ptas. less
      than CH. Marginal costs were 14,987 and 2,913 ptas. minor in HH than CH, per
      episode and day respectively. When we consider HH staff as a differential cost
      (i.e. to establish a new hospital at home unit with new staff) marginal cost per
      episode was 2,276 pesetas higher than CH. CONCLUSIONS: HH is a cost-effective
      option when decisions take into account the average cost (establishment of a new
      unit vs. a new ward) or when the HH unit is created as a substitute service
      through the conversion of pre-existent resources. However, HH is a disadvantaged
      cost option when it is created as an additional resource.

PMID- 9289550
TI  - [Infection by Strongyloides stercoralis in the county of Safor, Spain].
AB  - BACKGROUND: Strongyloides stercoralis is an endemic nematode in tropical and
      subtropical regions, but almost unknown in Spain. PATIENTS AND METHODS: In order
      to know some epidemiological, clinical and analytic features of this infection in
      our area (La Safor, Valencia), we performed a prospective study for 19 months.
      Through the search for the parasite in feces of patients with eosinophilia, we
      identified 37 subjects who were studied at diagnosis and 4 months later. RESULTS:
      Thirty-three patients (89%) were currently, or had been agricultural workers, and
      thirty had worked barefooted and/or had drunk contaminated irrigation water.
      Twenty-three patients (62%) had a chronic or immunosuppressive diseases, and two
      of them on steroid treatment, developed a disseminated strongyloidiasis. Thirteen
      patients (35%) were asymptomatic; the rest had clinical manifestations attributed
      S. stercoralis, mainly digestive. Two of the patients with disseminated
      strongyloidiasis also had concomitant bacterial infections by Streptococcus
      bovis, Streptococcus faecalis and Enterobacter sp. At diagnosis, besides
      eosinophilia, 86.5% had raised levels of IgE. Four months later treatment, the
      number of eosinophils was normal and IgE levels significantly decreased. The
      diagnostic yield of parasitic study of feces was increased with the number of
      samples examined. Thiabendazole achieved erradication of the parasite in 35
      patients, and the other two died because of disseminated strongyloidiasis.
      CONCLUSIONS: The presence of eosinophilia in patients from rural areas with
      subtropical climate should raise suspicion about infection by S. stercoralis,
      which, although sometimes is asymptomatic, may cause systemic bacterial
      infections in cases of hyperinfestation, specially when glucocorticoid treatment
      is given.

PMID- 9289551
TI  - [Apolipoprotein E and disease].

PMID- 9289552
TI  - [Neurologic development, morphogenic receptors and schizophrenia].

PMID- 9289553
TI  - [Massive pleural effusion secondary to pancreatic-pleural fistula as first
      manifestation of chronic pancreatitis. Report of three cases].
AB  - Patients with chronic pancreatitis develop massive pleural effusion in less than
      1% and its frequency as the first clinical manifestation of the disease is
      unknown. Three patients with massive pleural effusion and dyspnea which led to
      the diagnosis of chronic pancreatitis are referred. The patients were 28, 37 and
      41 years old, they were hard-drinking and they came to the hospital because of
      quick and progressive dyspnea, with hypoxemia and hypocapnia. Two patients had
      right and one left pleural effusion. The thoracothentesis gave 10, 9 and 3.5 l of
      serohematic liquid rich in pancreatic enzymes. All cases showed tomographic
      changes of chronic pancreatitis and pancreatic pseudocysts. Only in one of them
      the link between the pseudocyst and pleural effusion through a fistula in the
      right support of the diaphragm could be identified. The different therapeutic
      possibilities are discussed. Pancreatopleural fistula diagnosis should be
      considered in patients with massive fast pleural effusion and a history of high
      alcohol intake. High levels of pancreatic enzymes in the pleural liquid confirm
      the diagnosis.

PMID- 9289554
TI  - [Should moderate hypercholesterolemia be treated? New reasons for old opinions].

PMID- 9289555
TI  - [Atherosclerosis: a dynamic disease of the arterial intima with a chronic
      evolution in a predictable phase and an unpredictable phase].

PMID- 9289556
TI  - [Microangiopathic hemolytic anemia associated with acute brucellosis].

PMID- 9289558
TI  - [Familial essential thrombocythemia associated with von Willebrand disease].

PMID- 9289557
TI  - [The immune status against hepatitis A virus in medical residents].

PMID- 9289559
TI  - [Clinical-basic or basic-clinical investigation?].

PMID- 9289560
TI  - [Hypersensitivity vasculitis as a paraneoplastic manifestation prior to acute
      monocytic leukemia].

PMID- 9289561
TI  - [Rifabutin as a cause of curable visual alterations in patients with human
      immunodeficiency virus infection].

PMID- 9289562
TI  - [50 years since the Nuremberg code. Physicians under the Nazi regime were no
      reluctant servants].

PMID- 9289564
TI  - [Cloning, biobanks, multicultural meetings, medical turism....Medical ethics
      confronted with new challenges].

PMID- 9289563
TI  - [Torture and human rights 50 years after Nuremberg. The evil of the world today-
      seen from a physician's perspective].

PMID- 9289565
TI  - ["Doping control" may prevent scientific fraud. Scrutinize the raw material for
      articles and lectures before publication].

PMID- 9289566
TI  - [Several thousand years of experience do not prove harmlessness].

PMID- 9289567
TI  - [Accreditation may be a false quality label].

PMID- 9289568
TI  - [Improve the quality of quality work].

PMID- 9289569
TI  - [The time element should be considered in the article on the mildly retarded].

PMID- 9289571
TI  - [Economic intervals in the shipping of prescription drugs!?].

PMID- 9289570
TI  - ["Visual stress"--how to explain certain visual hallucinations?].

PMID- 9289572
TI  - [Normal life processes are ascribed to somatic disease].

PMID- 9289573
TI  - [Risk or advantage with repeated tests?].

PMID- 9289574
TI  - [The Adel reform causes problems with charges].

PMID- 9289575
TI  - [Forced lack of conformity in thyroid surgery].

PMID- 9289576
TI  - [Misleading information about the management of malignant melanomas].

PMID- 9289577
TI  - [The National Board of Health and Welfare does not have evidence (?) on
      statements about the interns].

PMID- 9289578
TI  - [I don't want to be reduced to a combination of numbers!].

PMID- 9289579
TI  - [Vaccination against chickenpox at age 12 should be tested].

PMID- 9289580
TI  - [Therapeutic alternatives in choledocholithiasis].

PMID- 9289581
TI  - [Laparoscopy possible even in cholelithiasis. Results for 96 patients from three
      different hospitals are reviewed].
AB  - At laparoscopic cholecystectomy, a procedure routinely used at Swedish surgery
      departments today, common bile duct stones are found to be present in 5-10 per
      cent of cases. During recent years, several alternative procedures have been
      evolved for the management of duct stones, such as operative or postoperative
      endoscopic sphincterolomy, or conversion to open surgery and choledochotomy. The
      article gives an account of laparoscopic treatment of common bile duct stones,
      and results obtained in 96 patients from three surgery departments in Sweden.
      Three different primary techniques were used: saline flushing via the
      cholangiography catheter, after intravenous injection of 1 mg of glucagon (in six
      cases of small stones); transcystic common duct exploration (TCDE), with
      cholodochoscopy and a Dermia basket (68 cases); and laparoscopic choledochotomy
      and choledochoscopy (22 cases). The success rate was 88 per cent (84/96), and
      mortality zero. In many cases the postoperative course was similar to that of
      patients undergoing laparoscopic cholecystectomy alone. We recommend TCDE in
      cases of common bile duct stones of no more than 8-9 mm in diameter, and where
      the cystic duct is large. Single-stage laparoscopic treatment of bile duct stones
      seems to be a safe and effective method of dealing with two problems in the same
      setting, and is an important alternative in the management of duct stones.

PMID- 9289583
TI  - [Bacterial cultures and follow up visits instead of penicillin. Diagnostic aids
      and free of charge follow ups can reduce the use of antibiotics].

PMID- 9289584
TI  - [Is there anything new under the sun? Historical pandemic and link to modern
      time].

PMID- 9289582
TI  - [Insulin as vasoactive hormone. Significance for diabetes, obesity and
      hypertension].

PMID- 9289587
TI  - [A year with pertussis vaccine].

PMID- 9289586
TI  - [The gene for hereditary pancreatitis discovered].

PMID- 9289585
TI  - [Is Good Clinical Practice necessary? How to avoid a painful experience].

PMID- 9289588
TI  - [How to investigate and treat sleep apnea syndrome? Medical specialty and place
      of residency may be decisive].

PMID- 9289589
TI  - [Hospital infections in intensive care units. Quick isolation is a beneficial
      measure].

PMID- 9289590
TI  - [Successful treatment of recurrent esophageal stricture. Steroids and dilatation
      resulted in permanent cure].

PMID- 9289591
TI  - [Skip routine prophylaxis in total hip alloplasty! The orthopedic surgeons decide
      the risk of thrombosis from case to case].

PMID- 9289592
TI  - ["Debriefing" -- psychological survey].

PMID- 9289593
TI  - Breast cancer gets the hard sell.

PMID- 9289594
TI  - Aspirin for bowel cancer: an old friend finds a new role.

PMID- 9289595
TI  - Interpretation of IST and CAST stroke trials. International Stroke Trial. Chinese
      Acute Stroke Trial.

PMID- 9289596
TI  - Deaths fom venous thromboembolism associated with combined oral contraceptives.

PMID- 9289597
TI  - [Snake bite during pregnancy].

PMID- 9289598
TI  - [Correspondence of the World Health Organization relative to the editorial by T.
      Ancelle (Med. Trop. 1996; 56: 347-348)].

PMID- 9289599
TI  - [Correspondence of the French Ministry of Cooperation relative to the editorial
      by J. Drucker and T. Ancelle (Med. Trop. 1996; 56: 345-346 and 346-348)].

PMID- 9289600
TI  - [Video-surgery in black Africa: apropos of 270 operations performed in Dakar].

PMID- 9289602
TI  - [Costa Rica, at the center of the Americas].

PMID- 9289601
TI  - [In the alphabet of hepatitis: the G virus].

PMID- 9289603
TI  - [Which vaccines for which travelers?].

PMID- 9289604
TI  - [Unusual mitral valve insufficiency].

PMID- 9289605
TI  - [The need to advance pharmaceutical innovation in tropical medicine: from
      incantations to reality].

PMID- 9289606
TI  - [Medical imaging in the topical environment].

PMID- 9289607
TI  - [Legal format and costs of prescriptions at the Central Hospital in Yaounde,
      Cameroon].
AB  - Prescribing treatment is the last act of a medical visit. A prescription is a
      written document that engages the medical and legal responsibility not only of
      the physician but of all those subsequently involved in its execution. In
      countries with weaker economies and more limited health care insurance the costs
      of filling a prescription can place a heavy financial burden on the families. In
      the present study we analyzed 285 prescriptions written in the Emergency Room and
      Outpatient Clinic of Central Hospital in Yaounde, Cameroon. In most cases
      prescribers were in compliance with legal requirements regarding their identity,
      but in 20 to 30% of cases neither the name nor function of the prescriber was
      mentioned. Most prescriptions were written legibly and coherently for both
      paramedical personnel and the patient. The number of products prescribed ranged
      from 2 to 5 depending on the issuing department. Practitioners in the outpatient
      clinic prescribed few brand-name products from the public outlet of the hospital
      pharmacy (16% of the prescriptions). In 68% of the cases a generic replacement
      was available. Practitioners in the emergency room were more apt to prescribe
      brand-name products (73% of the prescriptions). Five classes of drugs accounted
      for two thirds of prescriptions, i.e. analgesics-antipyretics, usual antibiotics,
      antimalarials, non-steroid anti-inflammatory drugs, and vitamins. Lawfully
      required information (drug presentation, route of administration, dose unit,
      directions and duration of treatment) was stated on 85% of prescriptions from the
      outpatient clinic and 50% from the emergency room. Although there were large
      variations, the mean cost of filling a prescription at the town pharmacy was
      identical in the two groups, i.e. 9500 CFA francs. The cost was 50% lower at the
      hospital pharmacy. All prescribers and in particular medical students should
      receive instruction in prescription writing. Careful selection of brand and non
      brand-name drugs in agreement with practitioners should achieve further
      reductions in the cost of filling a prescription in hospital pharmacy.

PMID- 9289608
TI  - [Seroprevalence of cysticercosis, taeniasis and swine infection on Reunion Island
      in 1992].
AB  - Cysticercosis is a parasitic disease commonly observed in developing countries in
      Latin America, Africa, and Asia. Many cases involving cerebral injury have been
      reported on Reunion Island, a French department in the Indian Ocean. The present
      article describes the findings of a seroprevalence survey performed from
      September 1990 to May 1992 using an ELISA technique. Out of a total of 1010
      individuals randomly selected from the voter registration records of the island's
      24 polling districts, 993 agreed to be interviewed and undergo blood testing.
      Samples from 14 individuals were positive for cysticercosis, indicating a
      seroprevalence of 1.4% with 95% confidence interval from 0.7 to 2.1%.
      Seropositive individuals were evenly distributed throughout the island with no
      statistical difference regarding sex and age. A retrospective study showed that
      diagnosis of taeniasis was uncommon (less than 0.02% of stool examinations for
      parasites). Meat inspection records showed that no pork had be seized due to
      taeniasis since 1993 but raising of pigs by private citizens without veterinarian
      control is still widespread. Living conditions are improving and eradication of
      endemic cysticercosis seems achievable by enforcing zoning codes and educating
      people about the need for proper meat handling and treatment of taeniasis.

PMID- 9289609
TI  - [Evaluation of the treatment of malaria using a 3-day regimen of quinine in
      Dakar].
AB  - The efficacy of quinine treatment for Plasmodium falciparum strains remains
      sound. However reports of decreased sensitivity and resistance of some strains in
      Asia and East Africa indicate that current treatment regimens should be re
      adjusted. The purpose for the present study carried out in Dakar, Senegal, was to
      evaluate the local regimen for acute Plasmodium falciparum malaria using quinine
      at a dose of 20 mg/kg per day in two daily injections on 3 consecutive days.
      Thirty-seven patients with acute Plasmodium falciparum malaria including 10
      severe cases were treated using the standard regimen and followed up clinically
      and parasitologically from Day 0 to Day 7. On Day 7 parasites were still
      detectable in the blood of four patients for a failure rate of 10.8%. Persistence
      of parasites despite disappearance of clinical symptoms suggests that the regimen
      should be increased to 25 mg/kg per day for at least for 3 days or longer if
      symptoms persist. Due to its adverse effects and cost (10 times higher than
      chloroquine treatment), quinine treatment should be prescribed only for patients
      with severe malaria forms.

PMID- 9289610
TI  - [Evaluation of the nutritional status of children less than 5 years of age in
      Moundou, Chad: correlations with morbidity and hospital mortality].
AB  - The purpose of this study carried out in the pediatric ward of the regional
      hospital in Moundou, Chad, between June 1992 and May 1993 was to assess the
      prevalence of protein-energy malnutrition in children under 5 years of age and
      its relationship with various diseases and in-hospital mortality. A total of 1050
      children ranging in age from 1 to 59 months were hospitalized in the ward during
      the study period and included in the study. Nutritional status was assessed using
      weight-for-height (W/H) and height-for-age (H/A) charts. Diarrhea, dehydratation,
      malaria, anemia, acute respiratory infection, and meningitis accounted for 85.5%
      of the underlying diseases and for 76% of deaths. At entry into study the
      prevalence of malnutrition was 63.1% (W/H < -2 Z-score) including 37% with severe
      malnutrition (W/H < -3 Z-score) and 16.1% with stunted growth (H/A < -2 Z-score).
      Malnutrition was more prevalent in children under than over 2 years of age (80%
      vs. 42.7% respectively). The same trend was observed with regard to severe
      malnutrition. The prevalence of malnutrition was highest in children with acute
      respiratory infections or diarrhea (61.3% and 89.8% respectively). Mortality was
      significantly higher in severely malnourished children and malnourished children
      with respiratory infection especially at ages under 1 year. Death was attributed
      to malnutrition in 30% of cases. Better low cost nutritional care is currently
      feasible. The most cost efficient methods of fighting against this problem are
      prevention and education especially concerning breast feeding.

PMID- 9289611
TI  - [Mass ciguatera poisoning after eating barracuda in Mexico: prognostic and
      therapeutic implications].
AB  - Thirty patients were admitted to the Anti-Poison Center of Marseille, France, on
      the fifth day of ciguatera fish poisoning due to ingestion of the same barracuda
      in Mexico. The purpose of this prospective study conducted during management of
      this group was to identify prognostic factors and evaluate the efficacy of
      treatment using mannitol. Upon admission severity was individually scored based
      on clinical findings. Twenty-two patients exhibiting the highest severity scores
      were immediately treated by infusion of 250 ml of 20% mannitol within one hour.
      These patients presented low plasma cholinesterase levels. Treatment led to
      transient improvement mainly with regard to cramping and digestive
      manifestations. All patients who presented high severity scores upon admission
      reported persistent manifestations lasting between 1 and 7 months. In 6 of these
      patients symptoms recurred after ingestion of seafood and/or alcohol. The fact
      that the extent of clinical symptoms in terms of severity and duration was
      correlated with the amount of fish ingested confirms that ciguatera poisoning is
      dose-dependent in man. However cholinesterase levels were not correlated with the
      severity of clinical manifestations.

PMID- 9289613
TI  - [29 cases of malaria introduced into New Caledonia from 1992 to 1995].
AB  - Although located in a tropical zone of the South Pacific, the island of New
      Caledonia is malaria-free. This retrospective study of imported malaria was
      conducted jointly by the Pasteur Institute of New Caledonia and the Gaston
      Bourret Territorial Hospital between January 1, 1992 and December 31, 1995. A
      total of 29 patients were hospitalized for malaria. Most contracted the disease
      in Vanuatu. Plasmodium vivax was involved more often than Plasmodium falciparum
      (22 vs. 11). No case was severe, complicated, or fatal. In most cases treatment
      consisted of quinine followed by mefloquine. The median duration of
      hospitalization was 5.7 days. Since the annual incidence of imported malaria is
      significantly higher in New Caledonia than in France, the authors propose that a
      Travelers Information Center should be set up in New Caledonia to improve
      prophylaxis against malaria.

PMID- 9289612
TI  - [AIDS and HIV infection in the Federal Islamic Republic of Comores (1988-1995)].
AB  - Since 1991 AIDS and HIV infection in the Federal Islamic Republic of the Comoros
      have been monitored through a network of sentinel sites including predetermined
      target populations. In all cases seropositivity for HIV was confirmed by western
      blotting after two ELISA screening tests. AIDS was diagnosed on Bangui clinical
      criteria and positive western blotting results. As of June 30, 1996, the
      cumulative number of AIDS cases reported to the World Health Organization was 7
      for a prevalence of 1.4 per 100000 inhabitants. The prevalence of HIV antibodies
      has remained at less than 1% in target populations, i.e. women undergoing
      prenatal examinations, patients with newly diagnosed tuberculosis, blood donors,
      and patients presenting sexually transmitted diseases (STD). This low stable
      prevalence rate which is similar to those reported in other Indian Ocean
      countries is in sharp contrast with the high incidence of syphilis and STD in the
      region.

PMID- 9289614
TI  - [Recurrent varicella and HIV infection. Apropos of 10 cases seen in Lome].
AB  - Herpes-zoster is commonly observed in immunodepressed patients with HIV infection
      in Africa. It is due to reactivation of the varicella-zoster virus. Varicella
      which is usually considered as the acute invasive phase of infection can recur in
      the same subject during immunodepression, thus constituting recurrent varicella.
      Little information is available concerning recurrent varicella in Africa. The
      purpose of the present report is to describe 10 cases observed in 9 adults and 1
      child in Lome, Togo. In 6 cases recurrence of varicella allowed diagnosis of HIV
      infection. Clinical symptoms were severe with widespread lesions and fever
      related changes in general status. Nine of the 10 patients required
      hospitalization. In all cases the illness lasted more than 3 weeks. This series
      demonstrates that varicella in adults can be the first clinical manifestation of
      HIV infection in tropical areas and that this possibility should be investigated
      especially if varicella is recurrent.

PMID- 9289615
TI  - [Epidemiology of supracondylar fractures of the humerus in children in Bangui,
      Central African Republic].
AB  - The purpose of this retrospective study was to evaluate the epidemiological,
      clinical, and anatomical aspects of supracondylar fractures of the humerus in
      children treated at the National University Hospital Center (NUHC) of Bangui,
      Central African Republic. Between January 1992 and March 1995 a total of 119
      documented cases involving children between the ages of 0 and 15 years were
      treated. Most patients were boys (62%) between 3 and 8 years of age. Fracture
      occurred during play in 74% of cases on the left side (92 cases) more often than
      the right. The mechanism of fracture was extension in 115 of the 119 cases with
      only four open fractures. Most fractures (68.1%) were severe (Lagrange Grade 3
      and 4). These findings which are comparable to those reported in other countries
      confirm the high incidence of supracondylar fracture of the humerus and need for
      appropriate treatment in African orthopedic facilities.

PMID- 9289616
TI  - [Current status of dengue virus infections. Epidemiologic and pathogenetic
      aspects].
AB  - The epidemiology of dengue fever is changing dramatically. The worldwide
      incidence is rising and clinical symptoms are worsening. Reports describing forms
      associated with hemorrhage or shock syndrome involving both children and adults
      are increasingly frequent in regions beyond Southeast Asia where the first cases
      were observed. Many mechanisms could be implicated in these changes including
      modifications of the virus, host, vector, or socioeconomic factors. Since no
      current model allows laboratory analysis of these mechanisms, observation of
      epidemics is still a major source of data. The findings of well conducted
      epidemiological studies allow not only assessment of morbidity and mortality in
      endemic areas and early detection of epidemic outbreaks but also evaluation of
      socioeconomic impact and effectiveness of control measures. Surveillance
      techniques must be chosen in function of prevailing local conditions. To ensure
      reliable results studies should be carried out in collaboration with an
      international network and a simple and accurate method of disease identification
      should be used.

PMID- 9289617
TI  - [Helicobacter pylori infection in developing countries].
AB  - Helicobacter pylori infection is probably the most common bacterial infection in
      the world. The pathogenicity of this bacteria has been recognized since 1989 in
      the developed world where prevalence is 20 to 40%. Its role in gastric and
      duodenal disease is certain and its low recurrence rate justifies eradication. In
      the developing world prevalence of Helicobacter pylori infection is over 80% with
      contamination being maximal in children. Transmission is oro-oral and even feco
      oral. Crowded living conditions is the determinant factor. Helicobacter pylori
      infection exhibits special features in developing world. The prevalence of
      gastroduodenal disease varies according to geographic area independently of the
      prevalence of Helicobacter pylori infection and stomach cancer is uncommon. In
      newborns Helicobacter pylori infection seems to be the primary event for chronic
      malnutrition and diarrhea syndrome with failure to thrive. In practice detection
      of Helicobacter pylori is difficult in the developing world and presumptive
      treatment is always followed by recurrence. In the future active or passive
      immunization will be the solution.

PMID- 9289619
TI  - [The organization of helicopter emergency services for the rescue of aircraft
      crash victims in the topical forest].
AB  - The purpose of this report was to describe lessons learned from experience in the
      tropical forest of Guyana and one helicopter rescue mission in that hostile
      environment. With previous data reported in the literature several guidelines for
      organizing these operations can be proposed. These rescue operations involve
      hoisting the victim to helicopter, medical treatment itself, and penetration into
      a hostile environment. Effectiveness and safety mandate that the physicians
      involved receive regular training in the techniques of helicopter evacuation,
      first aid, and survival. It is necessary to adapt conventional first aid kits for
      the purpose and to develop light and adequate survival equipment as listed
      exhaustively by the author.

PMID- 9289620
TI  - [Use of artemether in the treatment of severe malaria, an alternative in an
      unusual situation].

PMID- 9289618
TI  - [Buruli ulcers in rural areas of Benin: management of 635 cases].
AB  - Over the last six years we have treated 635 cases of Buruli ulcer at the Health
      and Nutrition Center of Zagnanado located in a rural area of southern Benin. Two
      thirds of cases involved children or adolescents from damp, swamp-land areas. The
      large size of this series and the fact that the number of cases increased yearly
      underlines the epidemic nature of this disease in Benin. Surgery was the only
      effective treatment and should be performed as early as possible. In our series
      of 635 cases wide excision of the ulcer and surrounding tissue was performed 797
      times and was followed by skin grafting using thin skin grafts in 574 cases.
      Antibiotic treatment was begun immediately in order to avoid or treat secondary
      infection which can be severe. Despite the primitive facilities available, in
      particular the necessity to harvest skin grafts using a plain razor blade, all
      patients recovered except 5 who died of intercurrent infection. Our experience
      confirms the efficacy of early treatment of the ulcer by wide excision associated
      with antibiotic treatment and followed by skin grafting using fine grafts.

PMID- 9289621
TI  - [Will a gametocytocide combined with an antimalarial schizonticide soon be
      necessary in areas of drug resistance?].

PMID- 9289622
TI  - [The status of antibiotic sensitivity of Vibrio cholerae 0:1 in Ecuador].

PMID- 9289624
TI  - [Efficacy of pyrantel pamoate in ascaridiasis in Vietmanese children].

PMID- 9289623
TI  - [A new epidemic of meningococcal meningitis in Burundi].

PMID- 9289625
TI  - [Antibiotics in animal husbandry].

PMID- 9289626
TI  - [Beta receptors and beta blockers in heart failure].

PMID- 9289627
TI  - [Multiple sclerosis].

PMID- 9289628
TI  - [Randomized controlled trials].

PMID- 9289629
TI  - [The presence of Human Papillomavirus (HPV) in microinvasive in situ
      spinocellular carcinoma of the oral cavity. Preliminary report].
AB  - BACKGROUND: The authors examined 15 cases of in situ and early oral SCC to detect
      the presence of HPV genoma. METHODS: They proceeded to in situ hybridization on
      paraffined specimens utilizing DNA-biotinylated fragments in commercial kit (Vyra
      Type in situ, Life Technologies, Gaithersburg, MD, USA). RESULTS: HPV-DNA was
      detected in 9 cases: 6/11, 16/18, 31/33/35 serotypes were detected. The
      distribution of viral serotypes by sites showed a prevalence of 16/18 serotype in
      tongue and floor of the mouth carcinoma, a prevalence of 6/11 serotype in
      gingiva, hard palate and buccal mucosa carcinoma, and 31/33/35 in commissura.
      CONCLUSIONS: The results suggest an important role of HPV in oral carcinogenesis,
      but further investigations are necessary to confirm these data on larger groups
      of patients to obtain a higher significance of the results.

PMID- 9289630
TI  - [Preoperative preparation for oral surgery of patients with underlying systemic
      diseases].

PMID- 9289631
TI  - [Sucralfate in odontostomatology. Clinical experience].
AB  - BACKGROUND: We here describe the pharmacological and pharmacodynamic
      characteristics of the molecule sucralfate, the aluminum subsalt of sucrose-8
      sulphate, introduced in Japan in 1968 as a mucoprotector for the treatment of
      peptic ulcers. For many years, attempts have been made to broaden the therapeutic
      indications of this molecule as has happened in oral medicine. This paper
      describes the results of the clinical trials reported in the international
      literature which were designed to investigate the use of sucralfate in the
      treatment of mucositis secondary to radio- and/or chemotherapy and during the
      course of recurrent aphtous stomatitis (RAS). METHODS: The authors carried out a
      pilot study with the aim of testing the efficacy and the tolerability of two
      formulations of sucralfate (20% suspension and 1 gram chewable tablets) in a
      total of 28 patients [14 with RAS: group A; and 14 with burning mouth syndrome
      (BMS): group B]. Each group was further divided into two subgroups [A1, A2, B1,
      B2] of 7 patients each. RESULTS: The results obtained in the RAS patients were
      encouraging, with an improvement in symptomatology in respectively 71.4% and
      42.8% of the patients in subgroups A1 and A2; a number of authors have previously
      suggested that this is due to a primarily mucoprotective mechanism similar to
      that occurring in patients with peptic ulcer. The results were less favourable in
      the BMS patients: symptoms improved in respectively 42.8% and 28.6% of the
      patients in subgroups B1 and B2, but worsened in 28.6% and 28.6% in teh same
      subgroups. CONCLUSIONS: In conclusion we believe that sucralfate can be
      considered a valid therapeutic support in the context of the lenitive
      pharmacological protocols in which it is currently used, but our results do not
      allow a definitive judgement of its efficacy in patients with BMS.

PMID- 9289632
TI  - [Clinico-diagnostic and odonto-stomatologic therapeutic problems in patients with
      HIV infection and AIDS].
AB  - During the last decade, scientific studies and new knowledges concerning HIV
      infection and AIDS, have constituted one of the main topics for discussion in the
      fields of biology and medicine. AIDS is a serious disease and it is unfortunately
      characterized by a very high death rate. In spite of all the efforts deployed by
      researchers and scientists, there is at present no effective therapy capable of
      restoring a proper immunological balance in the affected subjects. In the field
      of odontostomatology all diagnostic, clinical or therapeutic operation in HIV
      patients, is to be considered as particularly complex and characterized by some
      degree of real risk. It is therefore necessary to develop a whole set of health
      care models which must provide a broad range of different interventions in order
      to assure a rational and technically profitable service. We point to the various
      diagnostic, clinical and therapeutic methods and approaches to be recommended in
      the case of HIV and AIDS patients, and we add some reference to health care
      activities at the "San Luigi Center" of the Scientific Istitute San Raffaele
      Hospital in Milan.

PMID- 9289633
TI  - [Melanoma of the oral cavity. Review of the literature].
AB  - The location of melanoma in the oral cavity is extremely rare: its frequency
      varies between 0.2 and 8%. Oral melanoma strikes mainly male subjects and is more
      frequently seen at the level of the hard palate and gingiva. Today the
      clinicopathological classification of oral melanoma is not yet clearly outlined,
      and that is why the skin form is often taken as a reference. The acral
      lentiginous subtype proves to be the most common in this seat. In many cases (up
      to 50%) the diagnosis of melanoma is made on lesions which have evolved from the
      pre-existing pigmented lesions: as a consequence, every pigmented lesion of
      undetermined origin must be biopsied as a routine. The prognosis often proves
      poor and the surgical approach, combined with the chemotherapeutic one, is the
      first choice treatment. Lymph node dissection is not routinely practiced.

PMID- 9289635
TI  - [Mandibular cysts treated by decompression].
AB  - The authors reports a case of mandibular keratocystis treated using decompressive
      therapy and subsequent cystectomy after subtotal reduction of the cystic lacuna.
      The bone regenerative process was probably aided by the young age of the patient.

PMID- 9289634
TI  - [Clinical cases of teeth previously treated by endodontic restoration using intra
      canal pins of gold-coated brass].
AB  - The authors, in previous studies, showed that morphological alterations on gold
      coated brass pins, extracted after some years of staying in dental roots, are the
      consequence of a localized corrosion attack, produced by anaerobic bacteria,
      whose presence is confirmed by the high concentration of sulphur on the most
      attacked spots. Since, by using a suitable technique of pin inserting, the
      corrosion should not occur, it was supposed that root resorption could lead to
      favourable conditions to create corrosion. In order to bear out this assumption,
      10 meaningful clinical cases of teeth previously restored by gold coated
      radicular pins are critically evaluated.

PMID- 9289636
TI  - [Evolution of maxillo-malar osteotomy. Clinical experience].
AB  - Zygomaticomaxillary osteotomy is indicated in patients who have midfacial
      deficiency, a class III skeletal malocclusion and normal nasal projection. Many
      surgical procedures using an intraoral and an extraoral approach of the intraoral
      approach alone have been described. We prefer the intraoral approach because of
      the good aesthetic and functional results and the very low incidence of operative
      and postsurgical complications. As an alternative to these methods some authors
      have proposed a Le Fort I osteotomy associated with bone or alloplastic grafts in
      the malar region and a "high" Le Fort I osteotomy called quadrangular Le Fort I
      osteotomy. These techniques envisage total mobilization of the maxilla including
      the infraorbital rim. In our experience patients who have a scleral-show can
      undergo an osteotomy with infraorbital rim mobilization; patients who don't need
      a protection of the inferior sclera, instead, are advantageously treated without
      mobilizing the intraorbital rim. We illustrate our experience by reporting two
      out of 48 patients operated on using the intraoral approach.

PMID- 9289637
TI  - Risk of breast cancer in carriers of BRCA gene mutations.

PMID- 9289639
TI  - Risk of breast cancer in carriers of BRCA gene mutations.

PMID- 9289638
TI  - Risk of breast cancer in carriers of BRCA gene mutations.

PMID- 9289640
TI  - Risk of breast cancer in carriers of BRCA gene mutations.

PMID- 9289642
TI  - Sarcoidosis.

PMID- 9289641
TI  - Risk of breast cancer in carriers of BRCA gene mutations.

PMID- 9289643
TI  - Sarcoidosis.

PMID- 9289644
TI  - Sarcoidosis.

PMID- 9289645
TI  - Sarcoidosis.

PMID- 9289646
TI  - Sarcoidosis.

PMID- 9289647
TI  - Sarcoidosis.

PMID- 9289648
TI  - Cockroach allergen and asthma.

PMID- 9289649
TI  - Cockroach allergen and asthma.

PMID- 9289650
TI  - Artesunate and cerebellar dysfunction in falciparum malaria.

PMID- 9289651
TI  - Artesunate and cerebellar dysfunction in falciparum malaria.

PMID- 9289652
TI  - Treatment of bacterial infections.

PMID- 9289654
TI  - The validity of self-reported drug use: improving the accuracy of survey
      estimates. Proceedings of a meeting. September 8-9, 1994.

PMID- 9289653
TI  - Detection of Lyme disease after OspA vaccine.

PMID- 9289655
TI  - [Neurosurgical treatment of Parkinson's disease and other movement disorders.
      History].

PMID- 9289656
TI  - [Serial anatomy and MRI of the basal ganglia and the thalamus].

PMID- 9289657
TI  - [Anatomy and physiopathology of the basal ganglia].

PMID- 9289658
TI  - [Functional imaging].

PMID- 9289659
TI  - [Clinical features and current principles in medical treatment].

PMID- 9289661
TI  - Neurosurgical treatment of Parkinson's disease and other movement disorders.
      Bibliography.

PMID- 9289660
TI  - [Neurosurgical treatment of Parkinson's disease and other movement disorders.
      Marrakech, 25-28 May 1997].

PMID- 9289662
TI  - [The role of transvaginal ultrasonography in the screening of ovarian tumors].
AB  - BACKGROUND: From January 1992 to March 1996, 1987 women underwent vaginal
      sonography screening, at the Department of Obstetrics and Gynaecology of the II
      Faculty of Medicine and Surgery "Federico II" in Naples. This mass screening
      aimed at early diagnosis of ovarian cancer. METHODS: Patients included in this
      investigations were all asymptomatic and had no pelvic abnormalities. Each ovary
      was measured in three planes and ovarian volume was calculated using the prolate
      ellipsoid formula. In premenopausal women, ovaries were normal if their volume
      was of > or = 18 cm3 and if they were hypoechogenic or anechogenic. In
      postmenopausal women a normal ovary was defined as having a volume of > or = 8
      cm3 and a uniformly hypogenic internal structure. RESULTS AND CONCLUSIONS: In
      thirty-five premenopausal women was detected an abnormal volume of the ovaries.
      Forty-six postmenopausal women had abnormal vaginal sonograms. In this
      investigations vaginal sonography has permitted the detection of about 4.88%
      ovarian tumors in asymptomatic women, so that, it can be considered a more
      accurate and direment screening method for ovarian cancer than abdominal
      sonography.

PMID- 9289664
TI  - [Evaluation of bone loss in patient treated with Gn-Rh analogs].
AB  - BACKGROUND: The increasing use of analogs of Gn-RH during treatment of some
      benign gynaecological diseases, has induced the authors to investigate the
      principal collateral effects, fixing one's attention on the loss of bony mass.
      METHODS: This perspective research has considered 38 patients selected for two
      diseases "endometriosis" and "uterine fibromyomatosis". The therapy has been
      effected with triptorelin intramuscularly in a dose of 3.75 mg every 28 days for
      six months, in all six phials. RESULTS: After a half-yearly cycle of therapy, the
      loss of bony mass was valued about 3% medium. CONCLUSIONS: In the light of other
      studies too, it was decided to confirm the necessity of associating other
      medicines able to prevent the side effects caused by their analogs of Gn-RH.

PMID- 9289663
TI  - [Transvaginal ultrasonography vs. hysteroscopy. Study of 288 cases of abnormal
      uterine bleeding].
AB  - BACKGROUND: Abnormal uterine bleeding is the most common symptom of endometrial
      pathology. In the past, D and C (Dialation and Curettage) was the best way for
      both diagnosis and therapy. We used hysteroscopy in the study of endometrial
      pathology. The purpose of this study was to evaluate transvaginal ultrasound
      testing compared to hysteroscopy. METHODS: 288 women with abnormal uterine
      bleeding underwent transvaginal tests and hysteroscopies with biopsy and
      curettage. RESULTS: The study reported a 0.91 sensitivity and 0.89 specificity of
      the transvaginal probe. The authors consider the transvaginal examination a good
      to evaluate endometrial pathology. CONCLUSIONS: Furthermore, they have found the
      endometrial thickness and pattern with the TVG probe of value as the first step
      in any endometrial diagnosis, with or without bleeding.

PMID- 9289665
TI  - [Pattern of normal fetal heart rate in the third trimester of pregnancy].
AB  - BACKGROUND: It has been shown by previous studies that the mean fetal heart rate
      (FHR) decreases from the 11th to the 30th week, afterwards the values remain more
      stable. In the present study we evaluated the FHR pattern throughout the last
      stages of pregnancy and particularly we estimated the interindividual variability
      to achieve the maturation of the parasympathetic nervous system in the control of
      the FHR rythm. METHODS: Serial FHR determinations were made from the 28th week
      until term in 126 physiological pregnancies, submitted to umbilical Doppler
      velocimetry. The mean FHR was measured on the length of 6 cardiac beats. The FHR
      patterns of 48 healthy pregnancies, were also analyzed longitudinally. RESULTS:
      The transversal data, related to the 126 physiological pregnancies, show a
      further decrease of the FHR during the last stages of pregnancy: from the 28th to
      40th week it drops from the average value of 141 bpm to 133 bpm (r = -0.1469).
      The longitudinal data show that this decrease occurs in 27% of patients between
      the 30th and the 33rd week and in 73% of patients between the 34th and the 40th
      week. CONCLUSIONS: The conclusion is drawn that the physiological decrease of the
      mean FHR value occurs for each fetus at different gestational ages due to a
      different balance between the sympathetic and parasympathetic tone; moreover, we
      find that the interindividual variability in achieving the full maturation of the
      parasympathetic nervous system is quite wide.

PMID- 9289666
TI  - [Delivery in nulliparous women aged < or = 18 years].
AB  - METHODS: A retrospective study of 733 nulliparous women who gave birth at the
      Department of Obstetrics and Gynecology at the University of Bari, in the period
      from 1-1-1994 to 31-12-1995, was performed to evaluate the outcome of pregnancy
      and neonatal outcome in adolescents < or = 18 years old. The sample was
      subdivided into two subgroups; the first of 114 girls < or = 18 years old; the
      latter of 619 women 22-34 years of age, and they were compared. RESULTS: We have
      found a more lengthy term of pregnancy (39.66 weeks vs 39.27 weeks p = 0.008) and
      a greater incidence of vacuum extraction (VE) in the group of < or = 18 years old
      (7.89% vs 3.23% p = 0.03).

PMID- 9289667
TI  - [Hormonal contraception and benign breast disease. Evaluation of a treatment
      protocol for chronic mastopathy with mastalgia].
AB  - INTRODUCTION AND AIMS: The aim of this study was to study patients suffering from
      mammary nodules, fibrocystic disease and mastodynia. Having established the
      absence of malignant disease, the effect of EP (oestroprogestin) was evaluated in
      the treatment of fibrocystic disease with mastalgia. METHODS: From January 1990
      to December 1995 a total of 1921 women underwent breast examination at the
      "Centro di Fisiopatologia della Mammella" in the Division of Gynecology and
      Obstetrics of Iseo Municipal Hospital. Subjects were aged between 9 and 84 years
      old. The experimental protocol included a retrospective study of a group of 89
      patients suffering from chronic fibrocystic disease with mastalgia with a 3-month
      follow-up. The clinical examination was commenced by recording the patient's
      history and the measurement of the thickness of the gland and the evaluation of
      mastalgia represented important stages of the eco-clinical assessment. The
      setting for the study was the breast pathology out-patient clinic of the Division
      of Gynecology and Obstetrics. These women regularly attended our outpatient
      clinics for the following reasons: depistage, mastodynia, mammary secretion, self
      diagnosis of mammary nodules, checkups in patients during follow-up after surgery
      for genital neoplasia. All patients underwent clinical, echographic and often
      mammography/X-ray. Patients were selected on the basis of the following criteria:
      absence of malignant pathology and presence of chronic fibrocystic disease with
      mastalgia. Of those admitted to the study (no. = 89), only 59 completed the
      course. In addition to the absence of malignant pathology and the presence of
      chronic fibrocystic disease with mastalgia, the following parameters were
      assessed: measurement of the thickness of the mammary gland involving QSE before
      and after 3-month treatment with EP. The EP used were: gestodene 0.075 mg and
      etynylestradiol 0.03 mg-Minulet, or etynylestradiol 0.02 mg and dexogestrel 0.150
      mg-Securgin and Mercilon. RESULTS: The response to treatment was classified
      according to the 4 levels of the Cardiff Breast Score (CBS). The results were
      relatively good: 35.59% of patients showed a reduction in symptoms; 25.42% showed
      a marked improvement, and 18.64% a remission of symptoms. No effect was reported
      in 20.33% of patients. CONCLUSIONS: In conclusion, it may be said that EP
      treatment for 3 months can at least be proposed in patients with chronic
      fibrocystic disease and mastalgia given that a reduction and improvement in
      symptoms was seen in 60% of patients.

PMID- 9289668
TI  - [Mediterranean anemia in 124 Sicilian pregnant women].
AB  - INTRODUCTION AND AIMS: The aim of this study was to verify knowledge of beta
      thalassemia in a group of Sicilian puerpere. METHODS: The study was performed in
      a group of 124 pregnant women chosen at random from 2769 who gave birth in 1995
      in the third trimester of pregnancy at the Specialised Maternity Hospital of
      Santo Bambino in Catania. RESULTS: A total of 124 puerpere replied to the
      questionnaire out of 124 interviewed. Their age ranged from 15 to 46 years old;
      the most frequent age group was 20-35 years old (81 cases-65.4%). 69.3% (86
      cases) were married, 5.6% (7 cases) were separated or divorced, 24.9% (31 cases)
      were single or living with partners. The level of education was mainly lower
      (39.6%-49 cases) and upper (26.6%-33 cases) secondary school; there were few
      cases of illiteracy (3.2%-4 cases). The women were predominantly workers (25%-31
      cases), employees (37.1%-41 cases) and in 14.4% (18 cases) neither of the couple
      worked. 4% (5 cases) of women lived alone. 73.3% (91 cases) reported that they
      knew what Mediterranean anemia was, 85% (35 cases) had recently spoken about this
      pathology with their doctor, 57.2% (71 cases) with their gynecologist. 36.2% (45
      cases) knew the meaning of hemoglobinophoresis. 25% (31 cases) replied in the
      affirmative to the question regarding the hemoglobinophoresis test, 28.5% (35
      cases) were unable to answer and 46.7% (58 cases) replied negatively. 11.2% (14
      cases) of the puerperae had been informed about this disease when they were under
      20, 39.5% (49 cases) between 20 and 35 years old, and 0.80% (1 case) after 36
      years old. 36.2% of those interviewed (45 cases) responded correctly to the
      question "when does a carrier of Mediterranean anemia risk producing children
      suffering from a severe blood pathology?".

PMID- 9289669
TI  - [Ovarian granulosa cell tumor of juvenile type associated with pregnancy.
      Clinical case and review of the literature].
AB  - The granulosa cell tumor is the most common sex ovary stromal tumors. Ten percent
      of cases present during pregnancy. Two histopathologically well defined patterns
      of granulosa cell tumors are known: the common adult granulosa cell tumors (AGCT)
      and the less frequent juvenile granulosa cell tumor (JGCT). This report describes
      a case of juvenile tumor of the granulosa occurring in a 22 year-old pregnant
      woman.

PMID- 9289670
TI  - [Clinical-diagnostic considerations of a case of endometrial ossification as a
      cause of secondary infertility].
AB  - Endometrial ossification is a rare finding. Its aetiology and pathogenesis are
      controversial. However a history of previous abortion is usually present. It has
      variable clinical presentations. We report a case in which the patient presented
      with secondary infertility.

PMID- 9289673
TI  - Restraining a child for a procedure.

PMID- 9289672
TI  - Pediatric genital exam.

PMID- 9289671
TI  - [Cervical factor in sterility: treatment with intravaginal estriol].
AB  - BACKGROUND: The aim of our study was to evaluate the efficacy and tolerability of
      vaginal estriol in treating the isolated cervical factor. METHODS: Three
      different groups of patients were selected at random on the basis of the
      administered therapy (estriol, ethinyl-estradiol, bromhexine associated with
      gonadotropins). The patients (thirty in all) came to the Autonomous Sterility
      Department of the Niguarda Ca' Granda Hospital in Milan during the November 1994
      January 1996 period. The following parameters were evaluated: cervical score
      according to Insler, cervical pH; in vivo penetration test (PCT) at third and
      sixth cycle of treatment; evaluation of the hormonal profile during the ovulatory
      period of estriol, estradiol, LH and progesterone at the third and sixth cycles
      of treatment; any possible pregnancy. RESULTS: On the whole, 23 patients out of
      30 (76.6%) had a positive in vivo penetration test. Particularly, a more
      favourable result was observed in the group to which vaginal estriol was
      administered as it presented, at treatment end, a positive PCT in 90% of cases.
      Moreover, always in the latter group, a greater percentage of pregnancies (40%)
      was observed. CONCLUSIONS: The obtained results have demonstrated that the drug
      we have studied can be recommended as a valid therapy for the treatment of the
      isolated cervical factor of sterility.

PMID- 9289675
TI  - [Organ and tissue regeneration in lower vertebrate animals during space flight
      and after its completion].
AB  - The most important data obtained in studies of the influence of space flight
      factors on the limb and lens regeneration in the newt Pleurodeles waltlii have
      been summarized. Regeneration of these organs under the conditions of space
      flight and after its termination proceeded just as on the ground. However after
      the 7th, 13th and 16th days of space flight, a trend was shown toward
      acceleration of the limb and lens regenerates development according to the
      regeneration stages and synchronization of the achieved stages, which was
      accompanied in some cases by an increased proliferative activity of the
      regenerate cells. It was shown that in two groups of animals operated before the
      16-day space flight (I) and just after its termination (II) accelerated
      development of the limb and lens regenerates was observed. In group II, at the
      large bud stage, the index of 3H-thymidine labeled blastema cells was more than
      twice that in the control. The size of regenerates in groups I and II exceeded
      reliably those in the control. These results suggest a prolonged effect of space
      flight factors on the limb and lens regeneration. It was also shown that the
      capacity of the muscle minced 14 days before the flight for regeneration was not
      suppressed, although somewhat decreased. An electron microscopic study showed
      degenerative-atrophic changes in the intact hind limb muscle after the 16-day
      space flight. We believe that the phenomenon of synchronization and accelerated
      regeneration of the limb and lens observed in the most experiments are due to the
      effect of microgravity on the animals.

PMID- 9289674
TI  - [A new class of small RNP (alpha-RNP) containing antisense RNA in K-562 cells.
      III. The DNA-binding activity of nuclear alpha-RNP. The Signal Transmission from
      Growth Factors Group of the Medical Faculty, F. Schiller University, Jena,
      Germany].
AB  - DNA-binding activity of small nuclear alpha-RNP identified in acid-soluble
      fraction of chromatin of human proerythroleukemic cell line K-562 was studied
      using the technique of gel retardation. We found that nuclear alpha-RNP isolated
      from K-562 cells through treatment with dimethylsulfoxide, an agent inducing
      differentiation, acquire a capacity to specific interaction with Alu repeats of
      DNA leading to the formation of alpha-RNP-Alu-DNA complexes; nuclear alpha-RNP
      from cells that were not treated with dimethylsulfoxide do not show such
      capacity, although they are tightly bound with chromatin in the cell. Thus, the
      capacity of nuclear alpha-RNP to direct interaction with DNA Alu repeats
      appearing after the induction of K-562 cells to differentiation along erythroid
      pathway is an inducible property. We discuss hypothesis about the involvement of
      nuclear alpha-RNP in the control of expression of inducible genes at the level of
      chromatin and interaction with DNA.

PMID- 9289678
TI  - [An electron microscopic study of the structure of the spermatozoa from sterile
      males from a crossing of Drosophila virilis x Drosophila lummei].
AB  - Using electron microscope, we have studied structure of the tail region of
      developing spermatozoa in sterile hybrid males FB1 and F2 resulting from D.
      virilis x D. lummei crosses, as well as in fertile males of D. virilis. Multiple
      disturbances in the structure of spermatid plasma membrane have been found in
      sterile males. The membrane is interrupted in many points; this is particularly
      apparent in the outer thicker layer. The adjacent nucleus (AN) of spermatids of
      hybrids also differs from that in D. virilis spermatid. The crystalline
      ultrastructure in this case has a lower volume as compared with D. virilis, it is
      located asymmetrically within the AN and is displaced to the edge of that part of
      the AN, which is located closely to the bundle of contractile fibrils. At the
      stage of elongation, nonuniform inclusions of irregular shape, several times
      larger than globules of the crystalline structure, are located nonuniformly
      within this crystal-like structure. The membrane of the AN is interrupted in many
      points or is fully absent. Matrix consisting of a large number of small globules
      is distributed nonuniformly within the AN. It is concluded that the presence of
      multiple disturbances of spermatid ultra-structure is the main factor leading to
      lack of sperm mobility and, correspondingly, sterility of virilis-lummei hybrid
      males.

PMID- 9289677
TI  - [The expression of desmin and cytokeratins No. 8 and 18 in the nonhematopoietic
      cells of the rat liver].
AB  - During prenatal ontogenesis of mammals, liver plays a role as the hemopoietic
      organ. We have studied the distribution of hepatocytes (antigenic markers-
      cytokeratins No 8 and 18) and Ito cells (antigenic marker--desmin) in the liver
      and the interaction of these two cell classes with hemopoietic cells. At days 14
      and 15 of embryonic development, nonhemopoietic liver cells had many processes,
      expressed desmin and were stained with antibodies against cytokeratins No 8 and
      18. The amount of desmin-positive cells shortly diminished on day 16 of
      gestation, when embryonic hepatoblasts (prehepatocytes) acquired cubical shape
      and expressed only cytokeratins, but not desmin. Morphometric analysis had shown
      that the amount of cells expressing desmin in the liver during the prenatal and
      neonatal periods is greater, than in the adult organ. We have observed tight
      association of desmin-positive cells and their processes with hemopoietic cells
      during prenatal and early postnatal ontogenesis. It is proposed that in the
      embryonic liver, desmin-positive cells may play a role of stromal elements
      involved in embryonic hemopoiesis; they also may support hepatocyte development.

PMID- 9289676
TI  - [The role of eicosanoids and progesterone in the ovulation of the oocytes in the
      common frog].
AB  - Prostaglandin F2 alpha (1-5 micrograms/ml) stimulated ovulation in vitro of Rana
      temporaria oocytes in the absence of pituitary suspension and potentiated the
      effects of progesterone. The inhibitor of cyclooxygenase indomethacin (0.01-10
      micrograms/ml) decreased the rate of oocyte ovulation stimulated by the pituitary
      suspension. An increased pituitary suspension concentration decreased the
      inhibitory effect of indomethacin. Indomethacin did not affect oocyte ovulation
      stimulated by prostaglandin F2 alpha or progesterone. The inhibition of ovulation
      by the chloride channel blocker SITS (10 microM) is partly relieved by
      prostaglandin F2 alpha or progesterone but completely eliminated by their
      mixture.

PMID- 9289679
TI  - [The phenotypic diversity of the disorders of embryogenesis in Notch mutants].
AB  - We analyzed embryogenesis of two Notch mutants of Drosophila melanogaster: Notch
      84k35 and Notch-88n, and their compounds. Three types of embryonic patterns of
      the mutants with different doses of gene Notch. Neurogenesis of the head and
      ventral regions is differentially regulated by gene Notch. Two factors have been
      identifies that affect the direction of migration of the somatic mesoderm cells.
      The role of visceral mesoderm in formation of the proventriculus.

PMID- 9289680
TI  - [Corneal transplantation in Hungary. Data of the National Keratoplasty Registry
      1992-1996].
AB  - Upon the request of the National Transplantation Committee a nationwide
      keratoplasty register is functioning at the Department of Ophtalmology,
      University Medical School of Debrecen. Since then at the end of each year we
      collected data from the University Departments and Hospitals performing corneal
      transplantation concerning their keratoplasties and related activities. According
      to the acquired data the number of corneal transplantations performed in Hungary
      was 299 in 1992, 298 in 1993, 320 in 1994, 426 in 1995, and 479 in 1996.
      Keratoplasties in Hungary were performed in 6 University Departments and in 13
      Hospitals, all together in 19 institutions in the past five years. The
      overwhelming majority of corneal transplantations (in 1995 95.8% and in 1996
      96.4%) were penetrating keratoplasties. The ratios of lamellar keratoplasties in
      1995 and in 1996 were 3.0% and 2.5%, respectively. The ratios of
      sclerokeratoplasties were slightly above 1% in both years. The distributions of
      implanted fresh and preserved (eye bank) corneas were around 50-50% in these two
      years so, that in 1995 a somewhat more and in 1996 somewhat less preserved
      corneas were used. This ratio for preserved corneas was less than 20% in the
      period between 1992 and 1994. The law regulating the procurement and the
      transplantation of corneas is based on presumed consent and explicit objection
      which is the better type of regulation for the performance of keratoplasties in
      large numbers. The number of corneal transplantations in Hungary in the past
      years was close to the figures of industrial countries (England, Germany)
      calculated for similar populations, inspite of the fact that financing was in
      many respects unacceptable.

PMID- 9289681
TI  - [Data on cholesterol level screening of patients with ischemic heart disease in
      the light of the Scandinavian Simvastatin Survival Study].
AB  - The authors carried out a coronary heart disease risk factor screening on 1240
      people of two villages of Bekes county, Hungary. The prevalence of coronary heart
      disease among the 969 people 35-70 years old was 12.0%, in the different age
      groups varied between 0.8 and 20.9%. This high prevalence could be explained by
      the high occurence of the different risk factors. The results of cholesterol
      levels were analysed according to that of Scandinavian Simvastatin Survival
      Study. From 35-70 years old screened people with coronary heart disease 77 had a
      cholesterol level between 5.5 and 8.0 mmol/l. In these patients with 20-40 mg
      daily dose of simvastatin during 5.4 years long treatment from 7 predicted
      coronary death 3, from 17 expected non fatal myocardial infarction 5, from 13
      anticipated revascularisation procedures 5 would be preventable. The 5.4 years
      long treatment with 20 mg simvastatin calculated with the prices of July 1996 in
      Hungary would cost 292831 forints, from which 87847 has to be paid by the
      patient. If the decrease of hospitalization costs of the coronary heart disease
      patients treated with simvastatin is also taken into account, the drug treatment
      costs, according to the literature, could be reduced with additional 88%.

PMID- 9289682
TI  - [Adult-onset sex-linked familial hypophosphatemic osteomalacia].
AB  - Three patients (a grandmother, her daughter and her grandson) belonging to a 23
      number-kindred of five generations suffered from adult-onset, X-linked, familiar
      hypophosphataemic osteomalacia. According to the familiar anecdotes the great
      grandmother also had the same disease. The clinical diagnosis was documented by X
      ray pictures, scintigraphic and bone histological results, the laboratory
      diagnosis was proven by blood and urine analyses examined after phosphate
      loading. The youngest, 24-year-old patient was treated with daily 3 g phosphate
      and high doses of calcitriol for 2 years. As a new feature of our therapy, per os
      treatment with 1.25 micrograms calcitriol was supplemented by daily 2-4
      micrograms iv. bolus calcitriol for one week every month. The osteomalacia,
      causing serious symptoms and complaints, healed. Our treatment seemed to be safe,
      as renal functions, serum total and ionized calcium and PTH levels (including
      midnight values) remained in normal range. On the basis of our results this
      disease can be treated by administration of high doses of phosphate, provided
      that development of hyperparathyroidism is prevented by the coadministration of
      high doses of calcitriol.

PMID- 9289683
TI  - [Prediction of the result of high-risk coronary bypass surgery by positron
      emission tomography].
AB  - Coronary angiography revealed three-vessel disease in a 56-year-old male with two
      previous myocardial infarctions. Coronary bypass surgery was initially ruled out
      by cardiac surgeon because of the poor left ventricular function (EF: 23%),
      despite moderate viability signs during conventional isotope techniques. Positron
      emission tomography with 18FDG indicated a large periinfarction area of
      hibernating myocardium. Accordingly, coronary bypass grafting was performed.
      Postoperatively, the symptoms disappeared, the left ventricular wall motion
      abnormalities (with the exception of the scarred region demonstrated by PET)
      improved, and the global left ventricular function increased significantly. This
      case and the role of cardiac PET study for prediction of the result of
      revascularization are discussed.

PMID- 9289685
TI  - [History of the Numismatic Division of the Hungarian Society of Medical History
      1976-1996].

PMID- 9289686
TI  - [Immunopathologic changes in atopic dermatitis].

PMID- 9289684
TI  - [Merkel cell tumor].
AB  - Merkel cell cancer is a rare carcinoma arising from the neuroendocrin cells of
      the skin. The diagnosis is based on the clinical behaviour, histopathologic and
      ultrastructural findings and immunohistochemical results. An unusual case of
      Merkel cell carcinoma is presented. Mass from the umbiculus and a right inguinal
      lymph node was excised in a 63-year-old female. The histologic features of a
      typical, primitive small cell tumor combined with the immunohistochemical
      evaluations established the diagnosis. Rare polynuclear giant cells were focally
      present in our case. Patient was treated with combination of chemotherapy
      (Cisplatin, Etoposid) and radiotherapy. Control examinations showed complete
      respond. One year later metastasis developed. Resection of all known metastasis
      were performed. Two months after the laparotomy she died of metastatic disease.
      The autopsy did not reveal any other primary tumor. The capricious nature of the
      clinical course and the differences between this tumor and other carcinomas is
      emphasized.

PMID- 9289688
TI  - [Cardiovascular complications of pancreatis diseases].
AB  - Under physiological conditions, the pancreas scarcely influences the function of
      the cardiovascular system, although the hormones produced in the healthy pancreas
      (insulin, glucagon and somatostatin) affect the myocardial contractility in
      pharmacological doses. Among the diseases of the pancreas, the pancreatic tumours
      (insulinoma, glucagonoma and vipoma), furthermore the acute and chronic
      pancreatitis involve cardiovascular complications, which influence the outcome of
      the disease. Although the clinical picture is dominated by the metabolic changes
      of the excessively produced hormones in pancreatic tumours, the cardiac and
      vascular effects of the hormones may be considerable. In acute necrotizing
      pancreatitis, enzymes released from the pancreas and inflammatory mediators
      transform acute necrotizing pancreatitis into "multiple organ disease"; one of
      the important forms of this disease is the cardiovascular shock syndrome. One of
      the best-known complications of chronic pancreatitis is the pancreoprive diabetes
      mellitus, and beside that other, nonspecific cardiac alterations (e.g. ECG
      changes) may occur.

PMID- 9289689
TI  - [ACE inhibitor therapy of hemodialyzed patients].
AB  - Authors studied the daily dose of angiotensin converting enzyme inhibitor
      captopril and enalapril in patients with hypertension on regular hemodialysis of
      three hemodialysis units, and the relationship between the daily doses of
      angiotensin converting enzyme inhibitors and the number of simultaneously used
      other antihypertensive agents in the same patients. 104 out of 133 hemodialysed
      patients were treated with antihypertensive agents, 53 patients received
      angiotensin converting enzyme inhibitor. The data of 23 captopril treated
      patients in 3 dialysis units and data of 17 enalapril treated patients in 2
      dialysis units were used as the basis of the study. The difference between the
      average daily doses of captopril applied at the different hemodialysis units was
      significant (111, 61 and 26 mg/day). However the difference between the average
      doses of enalapril was not significant (18 and 12.9 mg/day). The correlation was
      found to be significant between the dose of captopril and the number of
      simultaneously used antihypertensive agents: r = 0.46, p < 0.05. The correlation
      was also significant between the dose of enalapril and the number of combinations
      of other antihypertensive agents: r = 0.50, p < 0.05. These relations and the
      analysis of antihypertensive therapy of 4 patients, receiving the largest doses
      of captopril suggest that larger doses of angiotensin converting enzyme
      inhibitors were used in the more resistant hypertensive patients, where more
      antihypertensive agents were needed to be administered to control the blood
      pressure.

PMID- 9289687
TI  - [Detection of human papillomavirus gene sequences in laryngeal tumors and
      premalignant changes by polymerase chain reaction].
AB  - Human papillomavirus gene sequences have been detected in a number of malignant
      and benign tumours. Non-oncogenic types 6 and 11 are etiological factors of
      benign mucosal tumours. Types 16 and 18 can be detected in malignancies most
      often but their role in the etiopathogenesis of cancers is still unclear. In our
      study we examined formalin-fixed and paraffin-embedded archive laryngeal tissues
      containing squamous cell carcinoma, papilloma and precancerous lesions for the
      presence of human papillomavirus genes. As a control we also examined tissues
      harbouring laryngeal nodules which represented the normal larynx in our study.
      After DNA preparation from the paraffin blocks we performed polymerase chain
      reaction to detect the DNA of human papillomavirus types 6, 11, 16 and 18. In the
      squamous cell carcinomas, papillomas and precancerous lesions the presence of
      human papillomavirus gene sequences was significantly higher than in the control
      group. To verify the integrity of DNA we also amplified a sequence deriving from
      the cellular beta-globin gene. Based on the 100% positivity for this gene we
      declare that the combination of our DNA preparation and polymerase chain reaction
      is a reliable method for detecting DNA sequences from formalin-fixed and paraffin
      embedded tissues.

PMID- 9289690
TI  - [Fatal sepsis due to long-term use of intrauterine device].
AB  - The author describes the case history of 36 years of age woman who developed
      generalised peritonitis with multiple abscesses in liver and brain having worn
      intrauterine device under no control by gynecologist for more than 15 years.
      During acute surgical intervention, abscess of the liver and interintestinale
      abscesses, were evacuated with excision of dead tissues. The patient underwent
      also oophorectomy with continuous postoperative peritoneal lavage and had been
      treated in intensive care unit for four days. She recovered, her bowel movement
      restored, her temperature returned to normal but she suddenly died due to
      cerebellar impactment caused by brain-abscess.

PMID- 9289692
TI  - [Bicentenary of the birth of Marton Csausz (1797-1860)].

PMID- 9289691
TI  - [Metastasis in metastasis].
AB  - Double metachron neoplasm was found in a 75 year-old man by the authors, myxoid
      chondrosarcoma as primer neoplasm of the right leg, and cecum adenocarcinoma. In
      the centre of myxoid chondrosarcoma's metastasis of the lung adenocarcinoma
      metastasis occurred. Metastasis in metastasis is a histological rarity.

PMID- 9289694
TI  - [Determination of melanogens in urine].

PMID- 9289693
TI  - [International medical congress in Moscow 100 years ago].

PMID- 9289696
TI  - [Age dependence of cerebral Tc-99m-ECD distribution between preschool and school
      age children and adults].
AB  - AIM: This present study deals with the question whether normal distribution of
      local cerebral blood flow (ICBF) agents in adults can be transferred to the age
      group of 4 to 15 years old children. METHODS: 23 children (age: 4-15 years, mean
      11 +/- 3 y) (group I) and 10 adults (age: 27-56 years, mean 45 +/- 10 y) (group
      II) without evidence of cerebrovascular disease or other brain diseases underwent
      Tc-99m-ECD-SPECT imaging. Counts in the cortical ROIs were related to those of
      cerebellar ROIs (= 100%). RESULTS: In group I, relative cortical activity
      exceeded that of group II, particularly in parietal (107.6 +/- 9.8 vs. 84.1 +/-
      12.4%), frontal (97.7 +/- 6.7 vs. 79.4 +/- 8.9%), left temporal areas (99.7 +/-
      7.4 vs. 84.9 +/- 10.1%) and in the singular cortex (112.1 +/- 9.1 vs. 95.9 +/-
      10.1%, p < 0.05). Cerebral activity uptake/injected dose/acquisition period was
      linearly correlated with age in group I (r = -0.78, p < 0.001). There was also a
      correlation of the relative local count density with age in 5 parietal ROIs (r = 
      0.42 to -0.57), in 2 frontal ROIs (r = -0.48), in 7 temporal ROIs (r = -0.42 to 
      0.58) and in 2 occipital ROIs (r = -0.44). In 14 cortical regions relative counts
      differed when subgroups of children aged 4-10 and 11-15 years were analysed.
      CONCLUSION: There are systematic differences between 4 to 15 years old children
      and adults regarding the normal distribution of ICBF. Diagnostic use of perfusion
      agents has to consider the respective age-adjusted normal flow maps; respective
      normal ranges should be determined for age groups of 4-10 and of 11-15 years
      separately.

PMID- 9289695
TI  - A role for microtubules in Plasmodium falciparum merozoite invasion.
AB  - Colchicine, a drug which poisons the polymerization of microtubules, was assayed
      for effects on the invasion of Plasmodium falciparum merozoites into red cells in
      order to investigate if merozoite microtubules have a function in invasion.
      Culture conditions and concentrations of colchicine were established where the
      maturation and rupture of schizonts was unaffected by the drug. This was judged
      first by light microscopy, including morphology and counts of nuclear particle
      numbers, then by ultrastructural studies which excluded deranged organellogenesis
      as a cause of merozoite failure, and finally by diachronic cultures in which both
      recruitment and loss of schizonts could be counted. Specific invasion inhibition
      was seen when 10 microM-1 mM colchicine was present. Red cells pre-incubated in
      colchicine and then washed showed no reduction in their extent of invasion, and
      neither red cell lysis, sphering nor blebbing were apparent. We conclude that
      intact microtubules are necessary for successful merozoite function.

PMID- 9289697
TI  - [Prediction of pharmacological effect of octreotide in acromegaly by means of
      111In-pentetreotide scintigraphy and calculation of a pituitary uptake index].
AB  - AIM: The aim of our prospective study was to optimize the determination of the
      pituitary somatostatin receptor status by means of 111-In-pentetreotide
      scintigraphy and to compare it intraindividually with the pharmacological effect
      of octreotide in active acromegaly. METHODS: In n = 22 patients with growth
      hormone (GH) secreting pituitary adenoma, 111-In-pentetreotide scintigraphy was
      performed, and the specific radionuclide accumulation in the pituitary area
      (evaluation visually as well as semiquantitatively by means of ROI technique and
      calculation of various uptake indices) was correlated with the acute drop of GH
      after administration of 100 micrograms octreotide s. c. (octreotide acute test).
      RESULTS: The uptake index we propose (cts/pixel-ratio circular pituitary ROI:
      irregular cerebrum ROI after background correction in the sagittal SPECT slice
      with maximum pituitary uptake 24 h p.i.) correlates best with the pharmacological
      effect (acute decrease of GH levels) of octreotide; its upper normal limit
      amounts of 3.5. CONCLUSION: As often the normal pituitary gland can be visualized
      scintigraphically, the purely visual differentiation between a normal and a
      pathological receptor status sometimes is equivocal. A pituitary uptake index,
      calculated by means of a standardized ROI technique, facilitates this
      discrimination and so contributes to select possible responders for a treatment
      with octreotide.

PMID- 9289698
TI  - [18Fluoro-FDG SPECT for the demonstration of hibernating myocardium: an interim
      account].
AB  - AIM: The present investigation demonstrates an intraindividual comparison of FDG
      PET and FDG-SPECT. MATERIAL AND METHODS: Thirty patients with CHD and planed
      revascularisation underwent both modalities. Myocardial perfusion was evaluated
      by 99mTc-MIBI SPECT. The myocardium was divided into 25 segments and the results
      were compared by two experienced observers. RESULTS: Segmental concordance of FDG
      PET and -SPECT was 94.1%. PET indicated a higher percentage of hibernating
      myocardium (8.9% vs. 5.7%) and a lower rate of matched defects (11.5% vs. 16.0%).
      In 22 cases the need for revascularisation was assessed identically. In the
      remaining 8 patients FDG-PET and FDG-SPECT required an intervention in 6 and 2
      cases, respectively. CONCLUSION: The results of FDG-PET and FDG-SPECT showed a
      high segmental concordance, but the individual assessment of hibernation
      worthwhile for revascularisation demonstrated important differences in patient
      management.

PMID- 9289699
TI  - [Intra-individual comparison of gastric peristalsis after ingestion of a
      semiliquid and solid test meal].
AB  - AIM: Patients with various disorders of gastric function were studied with
      radiolabeled test meals of different consistency to elaborate the effect of
      ingested media on gastric peristalsis and emptying. METHODS: In 12 patients
      parameters of gastric function were intraindividually compared after ingestion of
      a semiliquid and a solid test meal. In addition to the standard evaluation
      derived from time activity curves condensed images were established from two
      fixed time intervals (early and late period). These images were used to evaluate
      the amplitude and frequency of gastric contractions using Fourier analysis.
      RESULTS: As expected gastric emptying was influenced by the consistency of the
      test meal. Mean emptying rates for the solid meal were significant lower than
      those for the semiliquid one (p < 0.01). The amplitude and frequency of gastric
      contractions, however, did not depend on the consistency of the test meal. Within
      the course of the examination contraction amplitudes significantly increased (p <
      0.05) from the early to the late period using both, solid as well as semiliquid
      test meals. The frequency of gastric contractions remained unchanged. CONCLUSION:
      As shown by an intraindividual data comparison amplitude and frequency of gastric
      contractions seem to be independent of the consistency of ingested test meals
      whereas gastric emptying is significantly influenced by the administered media.
      Semiliquid meals offer advantages with respect to the shorter examination time
      and simpler preparation and therefore may be preferred for routine use. Since
      amplitudes seem to vary within the observation period standardized acquisition
      protocols are recommended for the evaluation of this parameter.

PMID- 9289700
TI  - [Double isotope albumin flux measurement: diagnosis and therapeutic monitoring of
      acute lung injury].
AB  - PURPOSE: Acute Lung Injury (ALI) is a clinical condition which is associated with
      a high lethality. It is characterized by an increased pulmonary capillary
      permeability and non-cardiogenic pulmonary edema. This study was designed to
      answer the question whether double isotope albumin-flux measurement is a useful
      tool both for diagnosis of increased pulmonary capillary permeability and for
      monitoring therapeutic interventions (nitric oxide (NO) inhalation). METHOD: In
      12 patients with clinical signs of ALI, transvascular albumin-flux was measured
      by a double radioisotope technique before, during and after NO inhalation. 99mTc
      labeled albumin and 51Cr labeled autologous erythrocytes were used as tracer. The
      radioactivity of both radiopharmaceuticals was measured externally over the right
      lung by a radiation probe and simultaneously in arterial blood. For
      quantification of transvascular albumin-flux Normalized Index (NI) and Normalized
      Slope Index (NSI) were calculated. Furthermore, pulmonal vascular pressures and
      other physiological parameters were recorded. RESULTS: All 12 patients showed
      markedly increased NSI before inhalation of NO. NSI decreased from 0.0074 +/-
      0.0046 min-1 without nitric oxide to -0.0051 +/- 0.0041 min-1 during nitric oxide
      and increased to 0.0046 +/- 0.0111 min-1 after nitric oxide. The decrease of the
      NSI correlated well with decrease of venous pulmonary resistance during
      inhalation of NO. CONCLUSION: Inhalation of NO reduces transvascular albumin-flux
      in patients with ALI. Double isotope albumin-flux measurement enables diagnosis
      of increased capillary permeability as well as monitoring therapeutic
      interventions.

PMID- 9289702
TI  - [Use of interferon alpha in treatment of hematopoietic and lymphatic system
      diseases].

PMID- 9289703
TI  - [Lymphoplasmacytoid lymphoma and the immune system in patients with this type of
      lymphoma].
AB  - Among 82 patients with L-LP in clinical stage IV, 14% were found to have
      monoclonal gammapathy and 22% polyclonal gammapathy. The other classes of
      immunoglobulins were not affected. In 78%, cell immunity was impaired. Decrease
      in T cell count (CD2+ and CD3+) in blood was found. Particularly T helper cells
      (CD4+), to a lesser degree T suppressor cells (CD8+) were affected. The life time
      of patients varied from 3 to 120 months. 60% of deaths were caused by infection.

PMID- 9289701
TI  - [Functional/metabolic CAD diagnosis: arbutamine-RNV, stress-Echo, Tl-SPECT and
      gated FDG-PET].
AB  - In this report we discuss the abilities of intercorrelative cardiovascular
      nuclear medicine to detect and characterize myocardial perfusion anomalies and
      viable myocardium in a 58-year-old patient before revascularization.

PMID- 9289704
TI  - [Primary forms of extralymphatic non-Hodgkin's lymphoma].
AB  - In 1981-1990, 584 patients with non-Hodgkin malignant lymphoma, 209 women and 375
      men, aged between 17 and 75 years, were treated at the I Department of Medicine
      and Department of Hematology, Silesian Medical Academy in Katowice. In this group
      the primary localization outside lymph nodes was seen in 26 patients (9 women and
      17 men), i.e. 4.6% of all patients with malignant non-Hodgkin lymphomas. Most
      frequently digestive tract was involved-19 patients (73.1%). Twenty three
      patients were treated surgically followed by chemotherapy and/or irradiation. Not
      operated patients were treated with either chemotherapy or both radio- and
      chemotherapy. Complete remission was achieved in 17 patients (65.4%), partial
      remission in 4 (15.4%) patients. Five patients did not respond to therapy
      (19.2%). A mean survival time was 49.4, 14.3, and 6.4 months, respectively.

PMID- 9289705
TI  - [Prognostic factors in patients with lymphoplasmacytic lymphoplasmacytoid
      lymphoma in stage IV of clinical progression].
AB  - Retrospective investigations were carried out in 50 patients with L-LP in
      clinical stage IV. All those patients died of this disease. The life time of the
      studied patients varied from 2 to 120 months and the median was 29 months.
      Advanced age, co-occurrence of anaemia and increased serum gammaglobulin level
      were found to be bad prognostic factors. No correlation was found between life
      time and tumour size, platelet number, lymphocyte count of blood and bone marrow.

PMID- 9289707
TI  - [Factors of liver damage in patients with acute leukemia].

PMID- 9289706
TI  - [Examination of human neutrophil activation in hyperlipidemia].
AB  - Chemotaxis, spontaneous migration, phagocytosis, expression of the receptors of
      Fc Ig fragments and of C3 component of complement has been examined in blood of
      51 patients with obesity divided into 3 groups with: 1. disturbances in
      carbohydrate and lipid metabolism, 2. disturbance in lipid metabolism, 3. no
      symptoms of metabolic diseases and 20 healthy controls. A comparison of the
      characteristics of neutral granulocytes in the blood of the healthy controls
      before and after fat rich meal has been performed. Obtained results indicate that
      high concentration of lipids, decrease granulocyte activity therefore could be
      the cause of the decrease of immunological defence.

PMID- 9289708
TI  - [Bone mineral disorders in patients with multiple myeloma].
AB  - The aim of the study was to evaluate bone mineralization in the patients with
      multiple myeloma. The examinations were performed in 49 patients (25 men and 24
      women). Seven patients were before chemotherapy and 42 patients were treated with
      chemotherapy. All of them received prednisone. The bone mineral density was
      measured by dual-energy X-ray absorptiometry with Lunar spine (L2-L4) in AP
      projection, femoral neck and total body were examined. There was a decrease of
      bone mineral density in 35 patients in at least one place (T-score more than 2 SD
      below normal of young healthy persons). There was no correlation between
      densitometric results and the duration of multiple myeloma, or chemotherapy. The
      decrease of bone mineral density (expressed es T-score) of lumbar spine (for the
      patients without spinal degenerative changes) was higher than that of femoral
      neck (p < 0.05). The decrease of bone mineral density (expressed as T-score) of
      lumbar spine and femoral neck was more pronounced than that of total body (p <
      0.001). Bone densitometry, especially of lumbar spine and femoral neck and less
      of total body is indicated in the patients with multiple myeloma. The result of
      this examination may be considered as an independent parameter of disease
      intensity.

PMID- 9289709
TI  - [Anxiety and depression during chemotherapy for lymphoproliferative diseases].
AB  - In order to analyse anxiety and depression states observed during the treatment
      of lymphoproliferative diseases, a group of 23 patients were studied. For
      assessment of the variables the following was used: history taking, psychological
      observation and psychometric techniques. The obtained results point to various
      dynamics of anxiety and depression. The intensity of anxiety states decreases
      during single as well as successive courses of chemotherapy. Depression states
      intensify during one course with a tendency for mood lowering with prolonged
      treatment duration. Therapeutic conclusions: 1. It is necessary to minimize
      anxiety attitudes, particularly during the first phase of the treatment
      (cognitive psychotherapy). 2. In deep depression it is indicated to use
      antidepressants and supportive psychotherapy.

PMID- 9289711
TI  - [Preliminary results of interferon alpha treatment for patients with chronic
      myelogenous leukemia].

PMID- 9289710
TI  - [Examination of interleukin levels and growth factor from blood platelets in
      leukemia].
AB  - Plasma concentrations of interleukines 1, 3, 6, 8 and platelet derived growth
      factor (PDGF) were estimated in 45 patients with leukaemias. Among patients were
      12 with acute myeloblastic leukaemia-AML (type M1 according to FAB
      classification), 9 with chronic granulocytic leukaemia-CGL, 10 with blastic
      crisis of CGL (CGL-BC) and 14 with chronic lymphocytic leukaemia-CLL (in 1 and 2
      stage according to Rai classification). Additionally the concentration of IL-3
      was measured in 10 patients with exacerbation of CLL. Control group consisted of
      12 health volunteers. The concentrations of interleukines and PDGF were
      determined by means of radioimmunoassay or immunoradiometric assay. In the
      patients with AML, CGL-BC and CLL significant increase of concentrations of IL
      1B, IL-6 were found. The patients suffers from CGL and CGL-BC had increase
      concentrations of IL-3, but patients with CLL-interleukin 8. The concentrations
      of PDGF were significantly decreased in the patients with AML, CGL-BC, and CGL.
      The differences of concentrations of studied interleukines can confirm their
      great significance in proliferation of leukaemic cells. The decrease of
      concentrations of PDGF in myelocytic leukaemias may reflect thrombopoietic
      disturbances in these illnesses.

PMID- 9289712
TI  - [Preliminary results of erythropoietin treatment of anemia in myelodysplastic
      syndromes and chronic lymphocytic leukemia].
AB  - Six patients with myelodysplastic syndromes (MDS) and two patients with chronic
      lymphocytic leukemia, all with severe anemia entered the study. Before treatment
      reasons of secondary anemia were excluded. Concentration of erythropoietin, iron,
      transferrin, ferritin were measured before, and in the second and the third month
      of the trial. A r-HuEpo dosage of 80 U/kg was administered intravenously three
      times weekly for a minimum of three months. Four patients finished the study. The
      increase in hemoglobin concentration by 6 g% was observed in one patient with MDS
      subtype RA. In three other patients who apart from r-HuEpo received chemotherapy
      transfusion requirements decreased by 90%. Together with increase in hemoglobin
      decrease in ferritin was observed. The correlation between r-HuEpo and endogenous
      erythropoietin and ferritin was defined.

PMID- 9289714
TI  - [Use of human recombinant granulopoietic colony growth factor rhGM-CSF combined
      with interferon alpha for preparation in preparation of a patient with hairy-cell
      leukemia for splenectomy].

PMID- 9289713
TI  - [Chronic granulocytic leukemia and an organ neoplasm in the same person].
AB  - Among 200 patients treated for chronic granulocytic leukaemia (CGL) 6 (3%) cases
      have been selected in whom a second synchronic or metachronic neoplasma
      coexisted. In one patient CGL was the first neoplasma and skin basalioma the
      second in line. In the remaining fife; Thyroid adenocarcinoma, adeno-carcinoma of
      the bowl (bis), epithelial carcinoma of the penis, epithelial carcinoma of the
      pulmonary, were followed respectively CGL as secondary tumor in same patient.

PMID- 9289715
TI  - [Deficiency of C2 component in a 9-year old girl].
AB  - The authors describe a 9 year-old girl with homozygous deficiency of C2
      component, causing null activity of the classical pathway of complement. The girl
      suffered from several recurrent infections since birth, later developed signs of
      the Henoch-Schonlein disease. At the age of 1 1/2 years she was hospitalized due
      to bacterial meningitis, most probably of Neisseria meningitis etiology.

PMID- 9289716
TI  - [Thyroid gland neoplasm in a child in remission from acute lymphoblastic
      leukemia].

PMID- 9289717
TI  - [A case of secondary amyloidosis in Hodgkin's disease].
AB  - A case of hepatic and intestinal secondary amyloidosis in 43 years old patient
      with Hodgkin's disease is presented. Diagnostic difficulties due to atypical
      localization of Hodgkin's disease were discussed. Therapeutic problems were
      caused by severe hepatic insufficiency.

PMID- 9289718
TI  - [Antiphospholipid antibody syndrome in systemic lupus erythematosus].
AB  - Various hemostatic abnormalities that can be met in the course of apparently
      unrelated diseases are caused by antiphospholipid antibodies (APA). Nearly on
      half of the population with antibodies detectable in serum suffer from systemic
      lupus erythematosus (SLE) or the disease will be diagnosed in the future. The
      supposition considering that APA do not bind phospholipids directly becomes
      popular recently. They bind serum beta 2-Glycoprotein. The APA-beta 2 GIP
      complexes speed up prothrombin activation and make beta 2 GIP less available for
      serum C- and S-protein transformation. APA are a heterogenous population of
      antibodies. Postinfectious APA differ from those found in autoimmune diseases.
      Thrombotic events caused by APA are treated according to general principles.
      Steroid therapy is essential in treatment programme of SLE with APA. In severe
      cases it is supplemented by intravenous cyclophosphamide. Plasmapheresis and
      intravenous immunoglobulins are of limited usefulness. In severe resistant
      thrombocytopenia one can try to introduce Danazol carefully.

PMID- 9289719
TI  - [Circulating immune complexes as markers of Hodgkin's disease activity].
AB  - Immune complexes may appear in autoimmune, lympho- and meyloproliferative
      diseases and in solid tumors. Literature data are presented on immune complexes
      in Hodgkin disease taking into account their prognostic importance in the course
      of the disease.

PMID- 9289720
TI  - [Informed consent--psychosocial barriers].

PMID- 9289722
TI  - [Linear prokaryotic chromosome; structure and synthesis of telomeres].

PMID- 9289721
TI  - [Nicholaus Copernicus as the precursor of mechanistic medicine (in the 450th
      anniversary of Nicholaus Copernicus's death)].

PMID- 9289723
TI  - [Organization and structure of genomes in Papilloma viruses].

PMID- 9289724
TI  - [Professor David Shugar awarded a honorary doctorate from the University of
      Warsaw].

PMID- 9289725
TI  - ["X"--the last unknown of hepatitis B virus? Gene X and products of its
      expression].

PMID- 9289726
TI  - [Oxidative damage of mitochondrial DNA associated with degenerative diseases and
      aging].

PMID- 9289727
TI  - [Rieske protein--a component of transmembrane cytochrome complexes].

PMID- 9289728
TI  - [Cooperation of phage and bacterial proteins in bacteriophage lambda DNA
      replication].

PMID- 9289729
TI  - [Protein C inhibitor: its properties, function and significance in equilibrium of
      hemostasis].

PMID- 9289730
TI  - [The battle against AIDS in not yet won].

PMID- 9289731
TI  - [Allow me some remarks on the views of the future in issue 6/96 pages 298-300].

PMID- 9289732
TI  - [Establishment of a work group on pharmacoepidemiology in the German
      Pharmaceutical Society].

PMID- 9289734
TI  - [The third edition of the European Pharmacopoeia and the German Pharmacopoeia].

PMID- 9289733
TI  - [The establishment and changes in ethical values in therapy and research].

PMID- 9289735
TI  - [The German Pharmaceutical Society--the regional group of Hamburg introduces
      itself].

PMID- 9289736
TI  - [Malaria].

PMID- 9289737
TI  - [Diphtheria, turning back an old epidemic?].

PMID- 9289738
TI  - [Aids].

PMID- 9289740
TI  - Caring for the patient.

PMID- 9289739
TI  - [Nevirapine--the first non-nucleoside inhibitor of reverse transcriptase in the
      battle against AIDS].

PMID- 9289741
TI  - Caring for the patient.

PMID- 9289742
TI  - Caring for the patient.

PMID- 9289744
TI  - Caring for the patient.

PMID- 9289743
TI  - Caring for the patient.

PMID- 9289745
TI  - Caring for the patient.

PMID- 9289746
TI  - The electronic Plant Gene Register.

PMID- 9289747
TI  - It isn't in the wrists?

PMID- 9289748
TI  - Child care--where to from here?

PMID- 9289749
TI  - [Pre-implantation evaluation using medical imagery: scanner or Scanora?].
AB  - A pre-implant investigation by way of medical imaging techniques may be effected
      by means of traditional X-ray cliches. However, a proper appreciation of the bone
      volume and the relations between the different bone structures is only possible
      by means of a three-dimensional evaluation. As a matter of fact, "sectional"
      pictures can be made by means of the "Scanner", but also by means of the
      "Scanora". The following article gives a detailed description of the "Scanora"
      technique and compares it with the "Dentascan" technique.

PMID- 9289750
TI  - [Radiation protection and quality assurance in dental radiography. A treatise
      from the European Community].
AB  - In general, the doses appearing during the dental examinations are relatively
      small, but as dental radiodiagnostics represents almost 25% of the entire
      radiological examinations in the European Union, some particular attention is to
      be paid to this kind of examination in terms of radiation protection. Article 2
      of the "patients directive" stipulates that dentists are to show some skills in
      the field of radiation protection. In addition they need to have enjoyed a proper
      training, aimed at the application of techniques in the field of dental
      radiodiagnostics. In order to make it easier for the Member States to execute
      this article, the commission has decided to draw up this text, containing some
      clear and understandable information on the proper use of radiological equipment
      and film development techniques, as well as on measures for radiation protection
      during dental radiodiagnostics, which will be to the benefit of both the patient
      and the personnel. The text is drawn up on the basis of the most recent
      technological concepts in this field.

PMID- 9289751
TI  - [Commentary on the treatise "Radiation protection and quality assurance in dental
      radiography". Scientific Commission of the Society of Dental Medicine].

PMID- 9289752
TI  - [Magnetic resonance imaging in oral medicine. Principle indications and contra
      indications].
AB  - MRI is the most recent of diagnostic imaging possibilities. It completes the
      information provided by panoramic X-rays and scanner. The technique is based on
      proton excitation within an intense magnetic field and does not release any
      ionizing radiation, as opposed to conventional images (panoramic and CT scanner).
      This technique is harmless, provided that known and continuously updated
      contraindications be complied with. Its major advantages include imaging within
      different spatial planes without moving the patient and its excellent tissular
      discrimination capacities. The latter quality accounts for spontaneous visibility
      of the TMA disc. Currently, it is the golden standard in exploring painful TMAs
      (internal derangements).

PMID- 9289753
TI  - [Digital radiology using the DIGORA registration technic].
AB  - Improvements in computer technology have brought about great changes in the
      manner in which X-ray diagnostics can be carried out. Both the registering and
      analysis of X-ray images can now be facilitated by the use of computer apparatus.
      The registering of X-ray images can be carried out with an X-ray sensitive sensor
      (CCD-sensor), which is inserted in the mouth and is linked to the computer by a
      thin cable. Another technique is based upon the use of storage phosphor plates.
      These are made of a material that can hold the latent X-ray image for some time
      after radiation and can be read by stimulation with laser light. The advantages
      of this method are that there is much similarity with the way in which X-ray
      photographs are registered on X-ray film and that the sensor is not connected to
      a cable. This latter quality allows one more freedom of movement in relation to
      the computer apparatus in the place were the X-ray photos are taken. Storage
      phosphor plates are less suitable than CCD systems for very precise quantitative
      measurement of X-ray photos. For diagnostic purposes, however, their picture
      quality is in no way inferior to that of CCD systems and of film-based X-ray
      techniques.

PMID- 9289755
TI  - [Digital image processing in orthodontics].
AB  - Digital image processing is an exciting and rapidly evolving technology that has
      become available for orthodontic purposes because of the constantly increasing
      speed and power of desktop computers, their peripherals and storage systems. This
      paper describes the typical hardware and some of the technical features and
      limitations of digital image processing in general. A critical review of its
      major applications in the field of orthodontics (i.e. growth and surgical
      prediction) reveals that the accuracy of the digital techniques is less than
      ideal, although image manipulation is faster and easter. Given the scientific
      limitations of contemporary digital image software, its major strength rather
      lies in its ability to improve patient communication.

PMID- 9289754
TI  - [Selection criteria for dental software].
AB  - Dentists who wish to introduce a computer based patient record system in their
      office are confronted with a lack of information concerning the selection of
      dental software. As wishes and demands concerning the content and options given
      by a dental computer program can vary widely from dentist to dentist and as
      dental software is changing rapidly a global objective evaluation is of no
      practical validity. Therefore a list of general and specific selection criteria
      was developed, enabling the practitioner to make a personal, objective comparison
      of quality of content versus wishes, price and service of different dental
      software programs. The criteria are discussed in this article.

PMID- 9289756
TI  - [Electronic communication in dentistry, 1996].
AB  - Computer network devices and systems have been introduced in dentistry for
      several years, but more and more software applications support not only the
      individual dentist as well as the complete dental profession in the progress for
      quicker information, better teaching and greater possibilities in postacademic
      education. Internet, Bulletin Board Systems. Electronic Mail and Computer Aided
      Learning are now very useful tools and will become indispensable and even
      essential in the near future.

PMID- 9289757
TI  - [Hypertext and expertext: how to navigate on an ocean of information].
AB  - Computers have made possible an explosive increase of information flow. In this
      ocean of information it becomes more and more easy to get lost. Computers again
      may provide answers to this problem. This article describes principles of small
      volume hypertext, large-volume hypertext and expertext as up-to-date navigation
      tools for the beginning as well as the advanced skipper. In addition, it is
      argued that the orthodontist should take responsibility in guiding these
      developments on his or her domain. He can do this by getting acquainted with the
      possibilities and choosing the right software. Ultimately, technology should not
      be developed for its own sake, but for the benefit of orthodontists and their
      patients.

PMID- 9289758
TI  - [Use of the computer in dentistry: video superimposition and facial reproduction
      using the expedience of the computer interface].
AB  - Both video superimposition and computer facial reproduction play a useful role in
      the process of identification, particularly in the early stages of an
      investigation or when other more definitive methods may not be available. Video
      superimposition combined with a computer overlay technique can be used to
      establish whether a skull outline matches an image of a missing person, being a
      photograph, slide or videoimage. A computer driven robot can be used to simplify
      the alignment of the skull with the position of the head on the image.
      Craniofacial or facial reproduction are used in both 2D or 3D to produce an image
      which can be used for identification purposes.

PMID- 9289760
TI  - [The uncertain boundaries between diabetes mellitus type I and type II:
      ketoacidosis in non-insulin-dependent diabetics].

PMID- 9289759
TI  - [Definitive or exploratory periodontal experimentation: an overview of the
      literature].
AB  - Definitive and exploratory randomized controlled trials (RCTs) have different
      goals as well as different design and analysis characteristics. The goal of
      definitive studies is to provide unequivocal evidence of a treatment's tangible
      benefit to the patient; a pre-trial-specified hypothesis is tested by use of a
      pre-trial-specified method. The goal of exploratory studies is to elucidate
      biological treatment mechanisms, to identify promising treatments, and to
      generate hypotheses for definitive studies: multiple hypotheses are evaluated to
      extract as much information from the data as possible. The purposes of this study
      were: (1) to survey selected design and analysis characteristics of randomized
      controlled periodontal trials published between 1988 and 1992 (n = 86), and (2)
      to classify trials as exploratory or definitive studies. The periodontal RCTs
      surveyed were typical of exploratory studies whose primary goal was to elucidate
      biological treatment mechanisms. Trial reports indicated the testing of multiple
      hypotheses (> or = 6 hypothesis tests in 70 of the 86 trials) on a variety of
      biological markers (86 out of 86 trials). The sample size (< or = 30 subjects in
      67 out of 86 trials), duration (< or = 6 months in 65 out of 86 trials), and
      design and analysis characteristics (e.g., an absence of masking in 57 out of 86
      trials) were also typical of exploratory studies which strive to obtain quick
      answers (short duration) at a low cost (small sample size; accept bias for
      increased efficiency and a lower cost). No definitive trials were identified.
      Promising, biologically active, treatments identified in exploratory trials
      should be evaluated in definitive studies where the primary goal is the
      procurement of unequivocal evidence of a treatment's tangible benefit to the
      patient. The costs and benefits of conducting definitive periodontal RCTs to
      provide such evidence should be investigated.

PMID- 9289761
TI  - [Mild hypercholesterolemia. Diagnosis and prognosis].
AB  - The finding of normocholesterolaemia, characterized by plasmatic values of total
      cholesterol < 2 g/l, which may hide silent lipidic alterations, is not by itself
      sufficient to rule out the existence of cardiovascular risk. First level
      screening of patients exposed to atherogenic risk must begin from dosage of three
      basic lipidic indicators, represented by total cholesterol, triglycerides, and
      HDL cholesterol. By using the values of the three above-mentioned indicators and
      by applying Friedewald's formula, it is possible to calculate LDL cholesterol
      indirectly. Atherogenic risk is present when HDL cholesterol and LDL cholesterol
      show plasmatic concentration inferior to 0.35 g/l and superior to 1,3 g/l
      respectively. The European Atherosclerosis Society lists five hyperlipidaemic
      classes, from A to E, determined on the basis of plasmatic levels of cholesterol
      and triglycerides. Mild hypercolesterolaemia associated with modest atherogenic
      risk and which largely occurs in people and is frequently underestimated form a
      diagnostic point of view, contributes to cardiovascular mortality more
      considerably than more serious forms of hypercholesterolaemia. On the basis of
      this observation, there originated the programmatic proposal for the prevention
      of hyperlipidaemic complications, presented by the Authors.

PMID- 9289762
TI  - [Clinical significance of Hurthle cell in the cytology of thyroid disease].
AB  - The natural history of Hurthle cell (HC) lesions has been the focus of a
      considerable debate. The difficulties in defining the malignant potential of HC
      has led to the current designation of HC tumor, with the implication that it may
      behave as either a benign or a malignant lesion. The objective of our study was
      to verify the clinical and prognostic relevance of the cytological diagnosis of
      HC in the thyroid lesion, 10,950 consecutive patients (F/M = 5.6/1) with thyroid
      nodules were evaluated by means of fine needle aspiration biopsy (FNAB).
      Cytological diagnosis showed the presence of HC in 285 cases (2.6%), with a F/M
      ratio of 8.2/1. In 123 cases (43.2%) cytologic diagnosis resulted benign. A
      suspicious pattern of follicular neoplasm was observed in 159 cases (55.8%). Only
      in 3 cases (1%) thyroid carcinomas were preoperatively identified. No false
      positive or negative cases were observed. Among the HC lesions, 85 patients
      (29.8%) underwent thyroid surgery because of a malignant or suspicious cytologic
      diagnosis, continuous nodular growth despite LT4 therapy, mechanical compression
      or clinical judgement. The other two hundred patients were clinically evaluated
      and, one year later, repeated FNAB confirmed the cytologic diagnosis of
      benignity. Among the follicular neoplasm nodules, 80 cases (55.3%) were
      surgically explored, and thyroid carcinoma diagnosed in 30 of them (37.5%), this
      percentage being greater than that observed in the group of non-HC follicular
      neoplasm (17%). Pathologic criteria for malignancy (vascular invasion,
      transcapsular penetration, destructive capsular invasion) were described in 25
      out of all carcinomas.

PMID- 9289763
TI  - [Anemia associated with chronic illness].

PMID- 9289764
TI  - [Pre-surgical medical therapy of hyperthyroidism].
AB  - The Authors analyze the use and the efficacy of antithyroidal drugs administered
      to the patients affected by hyperthyroidism, that must undergo thyroidectomy. The
      aim is that the patients arrive to the operation in euthyroidism: this is very
      important to avoid the complications that can occur during or just after the
      thyroidectomy. They believe that till today the most effective treatment of
      hyperthyroidism before thyroidectomy is based on the use of thyonamide and
      iodine. In case of intolerance to these drugs or if it is necessary an emergency
      thyroidectomy or in case of a low compliance of the patient, there is the
      possibility to use different therapeutic approaches with beta-blockers or
      betametasone plus iopanoic acid and propranolol administered together for a few
      days. As concerning the possible complications that can occur during or after the
      thyroidectomy, the Authors analyze in particular the thyrotoxicosis and the
      "hungry bone" syndrome.

PMID- 9289765
TI  - [Variations in the anatomy and physiology of the thyroid gland in old age].
AB  - Recently, the anatomical and physiological modifications of thyroid gland in the
      elderly have been undergone to many investigations. However, it does not exist an
      univocal interpretation about the results. Furthermore, non-thyroidal diseases,
      in the elderly, can modify TSH, FT3 and FT4 serum levels because of an important
      inhibition of T3 and T4 peripheric conversion; moreover, many drugs have been
      reported interactions with hypothalamus-hypophysis-thyroid axis in the
      senescence. At present, the international literature confirm, in the elderly, a
      reduction of the activity of the hypothalamus-hypophysis-thyroid axis, associated
      with an adaptation of hormones production; moreover, the thyroid gland undergoes
      anatomical (weight) and physiological (captation of iodine and hormones
      synthesis) adaptations, age-related, which witness for a reduction of thyroid
      function. Furthermore, FT3 and FT4 plasma levels present in old persons are
      comparable to younger subjects; in fact, in the elderly, it has been proved a
      reduction of T4 peripheric degradation which equilibrates its low production. So,
      the progressive reduction of thyroid gland activity in the old men must be
      explained like an adaptation to the new metabolic rhythm associated with a
      reduced TSH secretion and with a smaller body mass in the elderly. However, this
      peculiar new steady-state is not like an hypothyroidism syndrome, because there
      is not a real hormones reduction.

PMID- 9289766
TI  - [Multiple coronary revascularization using exclusively arterial bypasses
      (internal mammary arteries and the left radial artery)].

PMID- 9289768
TI  - [Percutaneous balloon dilatation of the mitral valve in a case of severe mitral
      stenosis].

PMID- 9289767
TI  - [How I treat onychomycosis using pulsed therapy].

PMID- 9289769
TI  - [Methods of hepatitis C virus transmission].

PMID- 9289770
TI  - [Pregnancy and cancer of the breast].

PMID- 9289771
TI  - [Ethical approaches in intensive care: restriction and/or cessation of treatment
      of patients in intensive care units].

PMID- 9289772
TI  - [The loss of autonomy in disabling neurologic diseases. Ethical considerations].

PMID- 9289773
TI  - [Ethics and economic imperatives in the distribution of care].

PMID- 9289774
TI  - [Euthanasia and assisted suicide: judicial and political developments in the
      Netherlands].

PMID- 9289775
TI  - [Ethical and legal considerations on euthanasia].

PMID- 9289776
TI  - [From the Hospice de la Misericorde to the Sart Tilman University Hospital
      Center].

PMID- 9289777
TI  - [How I examine cancer of the rectum using echoendoscopy].

PMID- 9289778
TI  - [Drug of the month. Fluvastatin (Lescol)].

PMID- 9289780
TI  - [Cerebral venous sinus thrombosis in a young women].

PMID- 9289779
TI  - [The mechanism of action of hypolipidemic drugs].

PMID- 9289781
TI  - [Clinical signs of connective tissue diseases in children].

PMID- 9289782
TI  - [Ventricular aneurysm or pseudoaneurysm?].

PMID- 9289783
TI  - [Superficial liposuction: a new treatment for lipodystrophies].

PMID- 9289784
TI  - [Some aspects of wound scarring].

PMID- 9289785
TI  - [Preeclampsia resulting from placental defects: biology to clinical
      considerations].

PMID- 9289786
TI  - [An often misdiagnosed cervical mass: carotid chemodectoma].

PMID- 9289787
TI  - [Cavernostomy: an old but effective technique in the treatment of pulmonary
      abscesses].

PMID- 9289788
TI  - [Question: phototherapy and newborn icterus].

PMID- 9289790
TI  - [Results of microsurgical reconstruction after vasectomy].
AB  - Because of the increasing number of divorces surgical refertilisation by
      vasovasostomy has become increasingly important. Of 33 patients operated in the
      last decade, 32 could be reached for follow-up. The patency-rate was 86% and the
      pregnancy-rate 28%. Possible explanations for this discrepancy are discussed. The
      time lag between vasectomy and vasovasostomy was the most important prognostic
      factor. There was no difference in the results between one-layer and two-layer
      anastomosis. With an interdisciplinary approach the same patency rate as
      described in the literature was achieved.

PMID- 9289789
TI  - [Can HIV/AIDS be healed with new therapies?].

PMID- 9289791
TI  - [Disorders of water- and electrolyte balance in a triathlon. 2 case reports and
      review of the literature].
AB  - Triathlon is an increasingly popular sport. The number of active triathletes in
      Switzerland has increased greatly in recent years. We report two participants of
      the Zurcher Euroman. Triathlon 1995, who presented with clinically significant
      water and electrolyte disturbance. The race took place on a hot day and both
      athletes ingested large amounts of hypoosmolar fluids during and in case 1, after
      the competition. Case 1 was a 27 year old woman who developed generalized
      seizures one hour after finishing the race. She had confusion which persisted for
      several hours. The initial serum sodium concentration was 118 mmol/L. Case 2 was
      a 29 year old man who collapsed during the triathlon and was confused for hours
      afterwards. He presented with a serum sodium concentration of 120 mmol/L. Both
      patients had massive polyuria (first hour urine output of 900 ml, and 1300 ml
      respectively) that decreased in parallel with the normalization of the serum
      sodium. The pathophysiology, differential diagnosis and therapy of electrolyte
      and water disturbances in triathletes is discussed in relation to our two cases
      and the literature is reviewed.

PMID- 9289792
TI  - [Is urine examination in urinary tract infection superfluous?].

PMID- 9289793
TI  - [Voluntary mercury poisoning: biological consequences and psychiatric
      significance].
AB  - A young patient suffering from schizophrenia had intense headaches and
      photophobia which were induced by intra-ocular injections of mercury. The
      clinical diagnosis was established once foreign bodies were visualized on regular
      X-rays of the patients skull. The mercury intoxication in combination with the
      secondary irreversible lesions to the eyes necessitated a bilateral enucleation
      and the use of a chelating treatment with sodium-dimercapto-1-propane sulfate
      (DMP). Automutilation is a very rare and dramatic complication of schizophrenia.
      The psychiatric handling and meaning of such dramatic automutilation is discussed
      in this case report together with a recent review of the toxicologic treatment of
      mercury intoxication in humans.

PMID- 9289795
TI  - [General practice case. Acute hepatitis A infection. Symptomatic and icteric
      course].

PMID- 9289794
TI  - [Follow-up and therapy of acute colchicine poisoning].
AB  - Colchicine poisoning is a rare event. Its outcome is, compared to other drug
      intoxications, often serious or even fatal. Intaxications with colchicine may
      occur by ingestion of tablets as well as by consumption of meadow saffron leaves
      (Colchicum autumnale) that are often mistakenly collected instead of the leaves
      of ramson herb (Allium ursinum). Colchicine poisoning typically shows three
      phases: initially gastrointestinal symptoms predominate, in the second phase
      multiorgan failure may occur possibly leading to death. In case the patient
      survives, the third phase of recovery follows during which the patients often
      present with hair loss. The fatal dose of acute colchicine poisoning is estimated
      at about 0.9 mg/kg. Since hemodialysis and hemoperfusion are not effective
      measures because of the high volume of distribution, an aggressive primary
      decontamination with gastric lavage and activated charcoal is required as early
      as possible. A promising new aspect in the treatment of heavy colchicine overdose
      is the immunotherapy with colchicine-specific fab-fragments. At present this
      treatment is still in an experimental stage and has been applied so far to one
      patient with beneficial effects. Unfortunately colchicine-specific antibodies are
      not yet commercially available.

PMID- 9289796
TI  - [Different methods of evaluation--object assessment of hair loss and alopecia].

PMID- 9289797
TI  - [Hair diseases: diagnosis and therapy].

PMID- 9289799
TI  - [Hair shaft anomalies].
AB  - Hair shaft disorders lead to brittle and uncombable hair. As a rule the hair
      feels dry and lusterless. Hair shaft abnormalities may present as localized of
      generalized alterations. Genetic predisposition and exogenous factors are able to
      produce hair shaft abnormalities. The most important examination to analyze a
      hair shaft problem is light microscopy. Treatment of hair shaft disorders should
      focus on the cause. In addition, minimizing traumatic influences to hair shafts,
      such as electric dryer, permanent waves and dyes is important.

PMID- 9289798
TI  - [Cycle of hair growth and evaluation of alopecia].
AB  - Hair follows a cycle of growth and involution which is asynchronous among
      follicles. Three phases are distinguished, namely the anagen growth phase and the
      catagen and telogen phases of regression. Any kind of alopecia results from
      perturbations of the hair cycle. Among triggering factors, various hormones,
      cytokines and apoptosis-inducing agents are currently recognized. Some
      microorganisms inducing inflammation could modulate the severity of selected hair
      loss disorders.

PMID- 9289800
TI  - [Cicatricial alopecias: diagnosis and therapy].
AB  - The cicatricial alopecias often are both a diagnostic and therapeutic challenge
      to the practitioner. Where there is no obvious physical/chemical injury or acute
      infectious etiology, clinical differential diagnosis of scarring alopecia is
      often difficult. The loss of follicular orifices in an area of alopecia points to
      a permanent loss of hair. In all of these cases a scalp biopsy is indicated.
      Primary and secondary scarring alopecia are differentiated: While the former is
      due to preferential destruction of the follicle, the latter results from events
      outside the follicle, which eventually impinge upon and eradicate the follicle.
      These include infiltrative processes such as granulomatous inflammation or
      neoplastic disease. In the group of primary scarring alopecia, well-defined
      chronic-inflammatory diseases of the scalp amenable to specific therapies are
      differentiated microscopically on the basis of the pattern of inflammation and
      the type of inflammatory cell that predominates. Thus, accurate diagnosis based
      on histopathology is a prerequisite to any rational therapy. Management of the
      less well classified diseases is much more problematic. Where end-stage fibrosis
      is established, surgical treatment and/or prosthetic help are taken into
      consideration. With the expanding knowledge of the immunology and molecular
      biology of the hair follicle, there is hope for the feasibility of therapeutic
      interventions that interfere early in the course of the pathogenetic processes
      ultimately leading to the permanent loss of hair.

PMID- 9289801
TI  - [Pathogenesis and diagnosis of androgenetic manifestations].
AB  - The endrocrinologic evaluation of androgenetic phenomena is complex and
      difficult. The targeted use of diverse hormone determinations and functional
      tests, of vaginal sonography and other imaging measures as well as selective
      catheterization of adrenal and ovarial veins in exceptional cases, however,
      permit efficient and precise diagnoses.

PMID- 9289802
TI  - [Current treatment of androgenetic male and female alopecia (with the exception
      of hormone treatment)].
AB  - Various non-hormonal therapies, either prescribed systemically such as certain
      hair-specific vitamins, or applied via the topical route, such as 2% Minoxidil,
      permit a normalisation of androgenic hair loss. The trichogenic action of these
      products should be verified in each individual with a comparative study using a
      trichogram and a phototrichogram. Any alopecia, be it large or small, may cause
      aesthetic discomfort. Currently, no medical or cosmetic product can give hope for
      a discernible and definitive hair regrowth. Only a micrograft reimplantation,
      hair by hair, produces tangible, aesthetically-denser hair in the bald region.

PMID- 9289803
TI  - [What is your diagnosis? Thalamic pacemaker].

PMID- 9289804
TI  - [Breath tests in intestinal diseases and functional gastrointestinal diagnosis].
AB  - Among the numerous breath tests described for gastroenterological applications,
      breath hydrogen (H2) tests have emerged during the past two decades as a most
      sensitive, reliable and feasible method for detecting carbohydrate malabsorption
      and maldigestion (e. g. lactose maldigestion). Hence they are regarded time
      honored standards of contemporary gastroenterological function tests. For the
      diagnosis of the small bowel bacterial overgrowth syndrome the glucose H2 breath
      test is a feasible tool with moderate sensitivity (approximately 65%), which,
      however, is not higher with alternative breath test (e. g. the 1 g 14C-D-xylose
      breath test). Measuring mouth-to-caecum-transit time by the breath H2 response
      after lactulose is more of scientific interest than clinically informative.
      Breath tests making use of 14C labeled substrates (usually 5 to 10 microCi) bear
      a rather low calculated radiation hazard and are thus in routine use in some
      countries, e. g. in Scandinavia, but they are abandoned in others. At least,
      however, radioactive 14C breath tests are (partially) dispensible, as these
      restrictions do not apply for the stable isotope 13C breath tests which are
      nonradioactive and thus devoid of any radiation hazard. For the purpose of
      gastroenterological function testing the 13C urea breath test for the detection
      of Helicobacter pylori infection, quantitative studies of gastric emptying with
      13C-acetate or 13C-octanoate and quantitative liver function tests have gained
      diagnostic use while 13C-breath tests assessing intestinal absorption or exocrine
      pancreatic function have been found less effective than the respective
      alternatives, or too expensive. Both, H2-breath tests and 13CO2-breath tests are
      clinically important, diagnostic methods with well delineated indications in
      gastroenterology.

PMID- 9289805
TI  - [Preserving continence in treatment of inflammatory bowel disease associated anal
      fistulas].
AB  - An overview of frequency, diagnosis, classification and therapy of perianal
      fistula in Crohn's disease is presented. There is a positive correlation with the
      extent of intestinal disease. The fistula as primary manifestation can present
      problems of differential diagnosis. Crohn fistulas may persist for an extended
      period of time without discomfort and complaints. Surgical treatment should be
      individualized for any given form of fistula. Hemorrhoidectomy in Crohn's disease
      associated with perianal fistulas should be avoided. Transspincteric and recto
      vaginal fistulas can be treated by peranal mucosal flap with good results. In
      summary, neither therapeutic nihilism nor hyperactivity is justified.

PMID- 9289806
TI  - [New therapeutic possibilities in chronic inflammatory bowel diseases].
AB  - New therapeutic measures in inflammatory bowel diseases (IBD) are either based on
      actual data on disease pathogenesis or on new pharmaceutic preparations of known
      drugs. An overshooting immune response with T cell activation in the local gut
      associated immune system seems to be central in the etiopathogenesis of IBD.
      Modulation of the antigenic load in the gut lumen by parenteral or enteral
      nutrition or antibiotic treatment can alter disease activity. Immunosuppressive
      drugs are able to decrease the overshooting immune response. Azathioprin has its
      clear value in chronic active steroid dependent disease courses of Crohn's
      disease. According to recent studies, Methotrexate seems to be active as well,
      however, more studies are necessary. Several studies were not able to prove that
      Cyclosporine is of value in the treatment of Crohn's disease. Newer preparations
      of aminosalicylates have shown effectiveness in both active disease and
      prolongation of remission in Crohn's disease in high doses. Local release
      formulations of steroids with high first-pass-effect as Budesonide will have
      their indication in subgroups of IBD patients. However, systemic steroid
      application is still the gold standard in active disease.

PMID- 9289807
TI  - [Stepwise diagnosis of intestinal hemorrhage].
AB  - Endoscopy is the method of choice in diagnosing gastrointestinal bleeding. In
      case of acute and severe bleeding a bleeding-source in the upper gastrointestinal
      tract has to be excluded with priority. The efficiency of endoscopy would be
      enhanced by endoscopic Doppler ultrasound. A diagnostic gap in the region of
      small bowel possibly will be closed by recently developed push-enteroscopy.
      Angiography and scintigraphy with labeled autologous erythrocytes are reserved to
      bleeding of still unknown source. Enteroclysis and double contrast barium enema
      are necessary only in very rare cases.

PMID- 9289808
TI  - [Neuchatel Tumor Registry : evaluation and results of 25 years of activity].

PMID- 9289809
TI  - Chlamydia pneumoniae. Proceedings of a meeting. Gavle, Sweden, 9-10 November
      1995.

PMID- 9289810
TI  - [Etiology, pathogenesis and pathophysiology of acute pancreatitis].
AB  - The etiology of acute pancreatitis is based on several causes, among which
      idiopathic nature (< 30%) is second to biliary stone disease (60-70%). It is
      still under debate whether alcohol as the main cause of chronic pancreatitic
      disease can cause acute pancreatitis. Based on Opie's "obstruction theory" of
      1901 and experimental data, it is now widely accepted that the gallstone passage
      into or through the terminal biliopancreatic ductal system triggers acute
      (necrotizing) pancreatitis by causing pancreatic ductal obstruction. However, the
      sequential intracellular mechanisms in the pathogenesis of acute pancreatitis
      remain unclear. A co-localization hypothesis has been proposed to explain the
      premature intracellular activation of trypsinogen to trypsin: due to a yet
      unknown defect in the intracellular protein transport and sorting system within
      the acinar cell, lysosomal hydrolases (i.e. cathepsin B) and secretory proteins
      (i.e. trypsinogen) co-localize in a fragile postgolgi vacuole where activation
      can occur. In addition, alterations of exo- and endocytosis at the apical pole
      exist (i.e. secretion block). The pathophysiological events are characterized by
      local and systemic hypovolemia and (micro)circulatory failure aggravating
      necrosis, followed by ARDS, renal failure and several other severe complications
      (i.e. sepsis and DIC). The systemic overflow of proteolytic enzymes (i.e. PLA-2)
      and kinins plays a major role as mediating factor in severe cases, resulting in
      multiorgan failure.

PMID- 9289811
TI  - [Etiology and perinatal medical significance of prematurity below 1,500 g].
AB  - 305 preterm babies with birthweight below 1500 g were delivered at our centre
      between 1991 and 1994. Classification according to etiology shows that more than
      half (52.7%) of these deliveries had to be induced secondary to underlying fetal
      or maternal pathology. A more efficient tocolysis could have prevented up to one
      third of these deliveries (31.4%). The main cause of each preterm delivery was
      defined according to Whitfield's etiological classification. In decreasing order
      of frequency we found hypertensive disorders of pregnancy, multiple pregnancy,
      preterm premature rupture of membranes, preterm labour and vaginal bleeding in
      the third trimester. The majority of these deliveries (88.6%) were prenatal
      referrals, reflecting widespread regionalization of obstetric services in
      Switzerland. Nevertheless, 64 women (24.2%) with threatening preterm labour
      before the 32nd week of gestation had to be denied admission to our hospital
      because of shortage of neonatal intensive care beds, or had to be transferred
      from our hospital to another offering perinatal facilities during the study
      period (1991-1994). Acute lack of neonatal intensive care unit beds in
      Switzerland requires closer attention in the future.

PMID- 9289813
TI  - [Fever: friend or enemy?].
AB  - Normal body temperature values are distributed in a Gaussian manner and are
      subject to circadian variation. Therefore, the usually accepted upper limit of 37
      degrees C for normal body temperature should be replaced by a value of 37.1
      degrees C in the morning and 37.4 degrees C in the afternoon. Fever develops when
      cytokines increase the thermostatic set point in the hypothalamus, which in turn
      results in increased body temperature via increased heat production and decreased
      heat dissipation. Hyperthermia is a distinct entity in which the thermostatic set
      point is normal but the heat control mechanism fails. Increased body temperature
      has positive effects (e.g. decreased bacterial growth, stimulation of host
      defence mechanisms) as well as negative effects (e.g. increased heart rate,
      oxygen consumption and metabolism). Whether fever is a friend or foe depends on
      the actual clinical circumstances. Antipyretic treatment should, therefore, not
      be applied routinely. In the case of pure hyperthermia (e.g. heat stroke),
      physical cooling is appropriate, while in the case of fever the thermostatic set
      point must first be normalized with drugs before cooling can be applied.

PMID- 9289812
TI  - [A young man with sore throat and infection].
AB  - Postanginal septicemia (Lemierre's syndrome) is an infection with anaerobes that
      ensues from certain oropharyngeal infections: septic thrombophlebitis of the
      internal jugular vein leads to abscess formation in the lungs and possibly in
      other organs. Based upon a recently observed typical case the syndrome is
      presented and its possible importance for empirical therapy of
      tonsillopharyngitis and septicemias involving unknown organisms is briefly
      discussed.

PMID- 9289814
TI  - [Guidelines for long-term home oxygen therapy in patients with chronic
      respiratory insufficiency. Swiss Society for Tuberculosis and Lung Diseases
      Control and Swiss Society of Pneumology].

PMID- 9289815
TI  - [New aspects in the treatment of bronchial asthma and chronic obstructive lung
      diseases].
AB  - The expansion of our knowledge regarding the pathogenesis of asthma has now made
      clear that it is an inflammatory disease. Although the treatment of bronchospasm
      associated with asthma is essential, it is important to consider the inflammatory
      aspect of the disease. The first therapeutic approach is to control environmental
      hazards (allergen, air pollution, tobacco smoke). It should always be remembered
      that patient education is of critical importance. Patients with only occasional
      asthma symptoms (2-4 times a week) should receive inhaled short-acting beta-2
      agonists as needed. Treatment with inhaled corticosteroids is instituted in all
      asthmatics except the mildest cases. Long-acting beta-2 agonists are an
      additional therapy for patients with unsatisfactory symptom control despite an
      optimal dose of inhaled steroids, particularly when there are nocturnal symptoms.
      Chronic obstructive pulmonary disease is defined as a disease state characterized
      by the presence of airflow obstruction due to chronic bronchitis or emphysema.
      Although the airflow obstruction is generally progressive, comprehensive
      therapeutic management benefits all patients including those with severe disease:
      stopping smoking, vaccination against influenza and pneumococcus, pharmacologic
      therapy. The judicious use of bronchodilators increases airflow and reduces
      dyspnea. Ipratropium and beta-2 agonists are equally efficacious and may work
      synergistically. The use of corticosteroids is controversial. Thus a closely
      monitored steroid trial of therapy should be considered in patients who have
      continuing symptoms or severe airflow limitation despite maximal therapy with
      other agents. Broad spectrum antibiotics are beneficial in severe exacerbations.

PMID- 9289816
TI  - [Choice of therapy in unifocal functional autonomy of the thyroid gland with
      hyperthyroidism].
AB  - Over the last 20 years, unifocal functionally autonomous nodes (UFA) of the
      thyroid have accounted for more than one third of all patients with
      hyperthyroidism in the former iodine-deficient and goiter-endemic region of Bern.
      This situation calls for a special diagnostic approach, i.e. etiologic diagnosis
      of any solitary nodule and careful consideration of therapy in contrast to
      regions with iodine excess where UFA is very rare, such as the USA. Therapy is
      recommended even where hyperthyroidism is still latent (blocked TRH test, normal
      TT3 and TT4) and reliably leads to subjective and objective improvement even in
      oligosymptomatic individuals. The safe and easy radioiodine therapy (RIT) is
      preferred in elderly patients with associated conditions. Surgical resection is
      recommended chiefly where malignancy is suspected or RIT is technically
      inappropriate. Both methods produce prompt eradication of the source of
      hyperthyroidism. The most frequent complication is hypothyroidism requiring
      lifelong follow-up.

PMID- 9289817
TI  - [Use of skin protective agents by patients with occupational dermatoses: need for
      improved preventive behavior].
AB  - QUESTIONS UNDER STUDY: In high-risk workplaces, primary and secondary measures to
      prevent occupational dermatoses are necessary. Therefore, protective creams as
      useful tools in prevention have to be applied adequate. The purpose of the
      present study was to determine whether a protective cream is adequately applied
      to the hands by patients with occupational dermatoses after self-application, and
      to quantify what areas are covered or missed. METHODS: 50 patients of the
      Department of Dermatology of the University Hospital, Zurich, suffering from job
      related skin diseases were recruited for a questionnaire and self-application of
      a cream as they would typically apply it. The cream contained 1% vitamin A
      acetate in order to fluoresce bright yellow when irradiated with Wood's light.
      RESULTS: 84% believed that their symptoms were occupationally-related. However,
      only 44% were occasional or regular users of protective creams and only 36% had
      previously been informed about skin protection at the workplace. Self-application
      of a fluorescent preparation resulted in many areas shown as skipped when viewed
      under Wood's lamp. Only 60% applied the test preparation sufficiently and the
      application was incomplete, especially in the dorsal aspects of the hands.
      CONCLUSIONS: Our results underline the necessity of educational efforts in the
      prevention of occupational dermatoses and present an effective approach to
      teaching patients the proper use of protective creams.

PMID- 9289818
TI  - [Inhalational antibiotic therapy in patients with cystic fibrosis and Pseudomonas
      infection].
AB  - Treating chronic Pseudomonas infection of the bronchial tree is a very important
      part of the treatment strategy in patients with cystic fibrosis. There are only a
      few antibiotics which are effective against pseudomonas. Many of them soon lead
      to bacterial resistance (e.g. fluoro-quinolones). Inhaling antibiotics produces
      high sputum concentrations and low systemic toxicity. Tolerance is good and
      resistance rare. Several clinical studies, some of them doubleblind placebo
      controlled, have shown a positive effect of inhaled antibiotics on symptoms, on
      frequency of necessary i.v. therapies and also on pulmonary function. Most
      commonly aminoglycosides (tobramycin) and colistin, which is not yet registered
      in Switzerland, are used. The main indication is chronic therapy of Pseudomonas
      infection.

PMID- 9289819
TI  - ["Subclavian steal syndrome"].

PMID- 9289820
TI  - [Primary pulmonary hypertension. Clinical aspects, follow-up and prognostic
      factors].
AB  - A retrospective study is presented of all patients with primary pulmonary
      hypertension (PPH) observed at Zurich University Hospital between 1980 and 1990.
      In 16 of the 36 patients (23 females/13 males, median age 40) there was a known
      risk factor for PPH: HIV infection (8), use of anorectic agents (7), liver
      cirrhosis (1). In 20 cases no risk factor could be found. In 4 of them PPH was
      diagnosed before the study period. We calculated an incidence of PPH in north
      east Switzerland of about 1.5 cases per million per year. The clinical course in
      the 20 patients without known risk factors for PPH was analyzed in more detail:
      treatment consisted of oral anticoagulation (15) and vasodilators (7); the median
      survival was 48 (1-307) months. Only 7 patients (35%) are still alive. Prognosis
      of PPH correlated with the severity of hemodynamics. The median survival in
      patients with pulmonary vascular resistance of < 1000 versus > or = 1000
      dyn.sec.cm-5 was 151 (106-307) months versus 13 (1-73) months (p < 0.001), with
      mean pulmonary artery pressure of < 50 versus > or = 50 mm Hg it was 151 (73-307)
      versus 13 (1-106) months (p = 0.0015), with right atrial pressure of < 10 versus
      > or = 10 mm Hg it was 90 (4-307) versus 3 (1-60) months, and with mixed venous
      O2-saturation of > or = 62% versus < 63% it was 119 (4-307) versus 14 (1-106)
      months (p = 0.024). PPH is a rare disease with a poor prognosis depending mainly
      on the severity of hemodynamic changes. However, despite this fact, the clinical
      course of individual patients may be unexpectedly favourable. Treatment of PPH is
      limited, and lung transplantation remains the most promising therapeutic
      approach. In this regard the quality of life aspect is of great importance.

PMID- 9289822
TI  - [Neurosyphilis 12 years after treatment of primary infection in a meanwhile HIV
      infected patient].
AB  - A 33-year-old male HIV-positive patient developed pure right motor hemiplegia due
      to meningovascular neurosyphilis. 12 years ago he was successfully treated for
      early syphilis with a single dose of 2.4 million units penicillin G benzathine
      without subsequent evidence of new infection or disease progression. Repeated HIV
      tests remained negative until 1993 when the HIV infection was diagnosed. It is
      well known that Treponema pallidum, the etiologic agent of syphilis, may be
      detected in the cerebrospinal fluid during early infection. Thus the former
      recommended regimen of single-dose penicillin G benzathine may not reliably
      eradicate T. pallidum from the CNS. Residual organisms may serve as a reservoir
      for relapse and dissemination in an immunocompromised host.

PMID- 9289821
TI  - [Aortic valve insufficiency in Crohn disease].
AB  - We report on a 39-year-old man with Crohn's disease who was admitted with
      cardiogenic shock after a short history of progressive dyspnea. Echocardiographic
      examination (transthoracic echocardiography) showed severe aortic regurgitation,
      mild mitral regurgitation, and enlargement of the sinus of Valsalva and of the
      ascending aorta at the level of the right pulmonary artery. The left ventricular
      ejection fraction was 30%. After aortic valve replacement, histologic examination
      of the ascending aorta showed chronic aortitis resembling syphilitic aortitis
      (serology for syphilis was negative) and HLA B27 related aortitis. The aortic
      valve showed deformation and thickening of the cusps by fibrous tissue without
      evidence of endocarditis. The patient remained well after surgery and
      echocardiographic examination 6 months later showed normal function of the aortic
      valve prosthesis. The diameter of the sinus of Valsalva and of the ascending
      aorta was slightly bigger, possibly indicating ongoing destruction. The left
      ventricular ejection fraction nearly normalized. It seems possible that this type
      of aortitis, characterized by its proximity to the valve ring, is another
      extraintestinal cardiac manifestation of Crohn's disease. The possibility of
      ongoing destruction of the sinus of Valsalva and of the ascending aorta after
      valve replacement makes regular echocardiographic control necessary.

PMID- 9289824
TI  - [Tumor in the abdomen?].

PMID- 9289823
TI  - [Rational intra-articular corticosteroid injection].
AB  - The intraarticular injection of corticosteroids has been a well known and
      effective therapy for rheumatoid arthritis and swollen joints of other, non
      infectious origin for almost 50 years. Today the indication for this intervention
      has to be more restrictive, and possible alternative therapies must be discussed
      with the patient. The number of injections in weight-bearing joints should not
      exceed three per year, and should no effect be noted, there is no reason to
      repeat an intraarticular injection. As there is a considerable variability in the
      details of administration of the injection, and the legal implications are
      currently changing, the practical aspects are discussed in this article. An
      extensive review of the literature leads to the distinction of actual knowledge
      from adopted faith and points out the relevant measures to minimize the risks and
      increase the benefits of the injection; most important is a precise and quick "no
      touch"-technique. The restrictive indication and a standardized practical
      procedure are the basis for successful intraarticular injection of
      corticosteroids.

PMID- 9289825
TI  - [Sports activity and risk of arthrosis].
AB  - Although the potential risk of exercise-induced osteoarthrosis (OA) of weight
      bearing joints such as hip, knee and ankle is of great public health importance,
      very little is known about it. One reason for this lack of knowledge may be the
      multifactorial etiology of degenerative joint disease, rendering it difficult to
      quantify the effect of an isolated factor such as exercise and sport on OA. The
      present review summarizes the current state of knowledge. Recent epidemiologic
      studies consistently find a slight increase in the risk of OA of hip and knee in
      those exercising very heavily, which is more marked in ball games than in
      endurance disciplines. Several epidemiologic studies (including the
      methodologically best ones) have investigated the effect of jogging on OA risk.
      They find that extremely active runners may be exposed to increased risk of OA of
      hip and knee that should not be totally disregarded. On the other hand, regular
      jogging in middle age is likely to help maintain physical function. A typical
      finding is that in former athletes the radiologic signs of degenerative joint
      disease appear to correspond more to the hypertrophic type (with osteophytes and
      subchondral sclerosis) than the destructive type (with joint space narrowing).
      This observation raises the question of the prognostic value of the radiologic
      signs observed in heavy exercisers. Accordingly, taking into account animal
      experiments and occupational studies as well, a slight increase in the risk of OA
      of weight-bearing joints due to very frequent and heavy exercise over many years
      cannot be entirely ruled out. However, for the majority of (less active)
      exercisers, recreational physical activity seems neither to increase nor decrease
      the risk of OA to any marked extent.

PMID- 9289826
TI  - [Heart rate, blood lactate concentration and subjective stress perception in
      submaximal running: new nomograms for assessment of endurance capacity].
AB  - Considering the protective effect of physical activity against coronary heart
      disease, the estimation of endurance capacity is not only recommended for
      sportsmen but is also useful for exercise counselling of unfit persons. Endurance
      capacity can be estimated with test protocols leading to complete exhaustion, or
      by submaximal test procedures. Submaximal tests have the advantage of putting
      less stress on subjects than maximal test protocols; on the other hand, they are
      less accurate. As a complement to traditional submaximal test protocols based on
      heart rate analysis, a new submaximal protocol is proposed based on measurements
      of capillary blood lactate concentration during exercise. Incremental tests of
      319 men with wide variation of endurance capacity were used to calculate
      nomograms of the typical pattern of exercise-induced increase in capillary blood
      lactate concentration, heart rate, and rating of perceived exertion in relation
      to endurance capacity. The running velocity eliciting a capillary blood
      concentration of 4 mmol/l lactate was selected as the parameter for endurance
      capacity. With the help of these nomograms, the 4 mmol/l-velocity could be
      estimated with submaximal values of lactate, heart rate or rating of perceived
      exertion. The appropriateness of the nomograms was checked against the data of
      100 independent maximal treadmill tests. Estimation of 4 mmol/l-velocity with
      submaximal lactate values showed good precision (with a small standard deviation
      of +/-0.17 m/s); in contrast, the estimation of endurance capacity with
      submaximal values for heart rate and rating of perceived exertion showed
      substantially larger standard deviations (approximately +/-0.56 m/s). We conclude
      that, for estimation of endurance capacity from submaximal running values, the
      nomogram for blood lactate concentrations can be recommended.

PMID- 9289827
TI  - [Detection of human herpesvirus 8 (HHV 8) in Kaposi sarcomas of the
      gastrointestinal tract].
AB  - Involvement of Kaposi's sarcoma in the gastrointestinal tract is common in AIDS
      patients. The disease is, however, usually asymptomatic and, due to the tumor
      growth primarily in the submucosa, biopsy diagnosis is possible in under 25%. The
      recently described human herpes virus 8 (HHV8) is closely associated with all
      forms of Kaposi's sarcoma. Detection of HHV8 in the tissue samples may therefore
      improve the diagnosis of gastrointestinal Kaposi's sarcoma. In the present study
      we analyze autopsy samples of tumor and non-tumor tissue from the
      gastrointestinal tract in patients with and without Kaposi's sarcoma for the
      presence of HHV8 DNA using a nested polymerase chain reaction (PCR) assay. HHV8
      DNA was present in all 15 tissues with Kaposi's sarcoma. In contrast, HHV8 DNA
      was present only in 3 (18.8%) of 16 gastrointestinal tissues of patients with
      Kaposi's sarcoma but without histologically detectable tumor. No HHV8 DNA was
      present in 15 tissue samples of AIDS patients without Kaposi's sarcoma. Our data
      show that detection of HHV8 DNA using a nested PCR assay is a highly sensitive
      and specific diagnostic test for Kaposi's sarcoma in autopsy tissue samples from
      the gastrointestinal tract. It should therefore be possible to use detection of
      HHV8 DNA in biopsy material as an assay for the diagnosis of Kaposi's sarcoma.

PMID- 9289828
TI  - [Cardiovascular surgery in Marfan syndrome. A review with case examples].
AB  - It has been clearly recognized that the diagnosis, management and long-term
      follow-up of operated and non-operated Marfan patients require a
      multidisciplinary approach. Despite the high quality of medical care in this
      country, the diagnosis of Marfan syndrome will be delayed in a majority of the
      cases even if the patient has already been treated for one of the aspects of this
      disease. Indications for surgery have recently been simplified. Regarding aortic
      and mitral valve regurgitation, the indications for surgical repair are similar
      to those of non-Marfan patients. The aortic root and ascending aorta should be
      replaced when the diameter reaches 50 to 55 mm. In children and adolescents,
      surgery is considered indicated when the diameter of the diseased aortic segment
      is more than twice the diameter of the normally expected aortic arch. This review
      presents a single center experience in the surgical treatment of cardiovascular
      manifestations associated with Marfan syndrome and summarizes some interesting
      cases treated in the recent past. Despite the progress made in the fields of
      surgery, anesthesiology, intensive care and cardiology, the mortality of acute
      surgery because of aortic dissection remains about 10% whereas elective surgery
      can be performed with a perioperative risk of around 2%. Even if composite graft
      replacement gives excellent long-term results, some alternatives to this
      technique should be considered, especially in patients in whom anticoagulation
      with cumadines is not recommended. More recently, a Working group for Adult and
      Teenager Congenital Heart Disease (WATCH) has been established within the Swiss
      Society of Cardiology, with the aim of optimizing the management of grown-up
      patients with congenital heart defects. Marfan syndrome was included in the
      recommendations of this group. Follow-up before or after surgery is recommended
      at yearly (or half-yearly) intervals and should include echocardiography and/or
      computed tomography or magnetic resonance imaging. Finally, the patient and his
      family should be informed about the prognosis of the disease, the technical
      options in the treatment of cardiovascular manifestations, and the possibility of
      assistance from the Marfan Foundation.

PMID- 9289829
TI  - [Experimental changes in the alveolo-capillary barrier induced by artificial
      ventilation].
AB  - Mechanical ventilation can have deleterious effects on the lungs. Extra-alveolar
      escape of air, such as pneumothorax or subcutaneous emphysema, are complications
      which have long been known. New experimental studies have clearly shown that
      mechanical ventilation can also result in pathologic changes to the air/blood
      barrier. Mechanical ventilation with high end-inspiratory pressure and high
      volume causes lung edema in whose origin abnormal permeability of the alveolo
      capillary barrier plays a major role. The abnormalities are in fact the result of
      pulmonary distention and not of elevated air pressure; this justifies the term
      "volume traumatism". The presence of a previous acute pulmonary injury
      considerably increases the deleterious effects of mechanical ventilation on the
      lungs. Although the clinical implications of these experimental studies are
      difficult to assess, they have nevertheless resulted in major changes in
      ventilation strategy for acute lung diseases such as the acute respiratory
      distress syndrome of the adult.

PMID- 9289831
TI  - [Kidney transplantation in the child].
AB  - The goal of treatment of end-stage renal failure in pediatric patients is a
      functioning transplant. Due to the serious shortage of cadaver kidneys, we have
      to consider living related donor transplantation (tpl) more frequently. Certain
      features are characteristic of pediatric patients before transplantation:
      underlying disease (over 2/3 are congenital or hereditary), the form of dialysis
      (automated peritoneal dialysis at home in young children) and the frequent need
      for tube feeding and treatment with growth hormone. Patients weighing 10 kg or
      more can be given an adult kidney. Young recipients are at risk for vascular
      thrombosis and hence the CVP should be kept high to allow good circulation, and
      continuous heparinization (10 units per kg and hour) is advocated. Minor
      rejection episodes may be overlooked in the presence of a large graft in a small
      child. Bladder dysfunction is a problem in many children with obstructive
      uropathy. Later on, viral infections (CMV, EBV) may pose serious problems since
      most children have not previously been exposed to them. Further problems are
      pyelonephritis in the graft and recurrence of the underlying disease. Long-term
      results are very satisfactory in terms of survival and quality of life including
      later social integration.

PMID- 9289830
TI  - [Perspectives in mechanical ventilation in ARDS].
AB  - Despite more than 25 years of extensive research, the mortality of ARDS patients
      remains high. The inflammatory process within the lung and the associated gas
      exchange disturbances require an aggressive ventilatory regimen, which itself may
      harm the lung. Therapeutic measures which are used to reduce iatrogenic damage to
      the lung are pressure controlled mechanical ventilation in combination with PEEP
      and permissive hypercapnia, dehydration and extracorporeal gas exchange. At
      present, new strategies such as intratracheal instillation of surfactant, partial
      liquid ventilation and inhalation of nitric oxide (NO) are being evaluated.
      Surfactant reduces the surface tension, forming a monomolecular layer at the
      air/tissue interface. It thereby decreases the forces necessary to expand the
      alveoli and prevents alveoli with small diameter from collapsing. In ARDS, a
      disturbance of surfactant synthesis, function and re-uptake is the rationale for
      treatment with exogenous surfactant. Initial clinical results suggest a limited
      positive effect independently of the surfactant preparation used, the dose and
      the application mode. Experience with partial liquid ventilation with
      perfluorocarbons in ARDS has also been reported. Perfluorocarbons are liquids
      with a high binding capacity for oxygen and carbon dioxide. During normal
      mechanical ventilation with gas, repetitive doses of perfluorocarbons are
      instilled into the lungs up to a volume equal to the functional residual
      capacity. The liquid is pushed into collapsed alveoli and keeps them open by
      reducing the surface tension. First clinical studies have demonstrated the
      possible improvement in pulmonary gas exchange. In ARDS, inhalation of NO may
      cause a predominantly selective vasodilation in blood vessels of ventilated lung
      regions, resulting in an increase in PaO2 and a decrease in pulmonary artery
      pressure. The effect of NO on the pulmonary vasculature also induces a reduction
      in right ventricular afterload and also in pulmonary capillary pressure, which
      may lead to a faster resolution of pulmonary edema. However, in spite of the
      promising results of these new strategies, further studies are needed to evaluate
      their influence on morbidity and mortality.

PMID- 9289832
TI  - [Life support for homeostasis in organ donors].
AB  - The main goal of intensive care of potential organ donors includes the
      maintenance of the organs' function with respect to their integrity after
      transplantation. Profound disturbances of cardiovascular, respiratory and
      endocrinological function may lead to early organ loss. Therefore, comprehensive
      therapy is required from the onset of brain death. The major dysfunctions and
      therapeutic goals in organ donors are summarized on the basis of current
      literature and our own findings.

PMID- 9289833
TI  - [Effectiveness of short-term triple therapy for healing Helicobacter pylori
      infection in ulcer disease].
AB  - There is evidence that triple therapy with two antibiotics and a proton pump
      inhibitor is more cost-effective than various dual therapies for the eradication
      of Helicobacter pylori. We have analyzed the effectiveness and acceptability of
      the so-called "Italian protocol" (clarithromycin 250 mg b.i.d., metronidazole 500
      mg b.i.d. and omeprazole 20 mg daily for one week, followed by 20 mg omeprazole
      daily for further 3 weeks) in a prospective study of 36 patients with
      Helicobacter pylori-associated ulcers (10 gastric ulcers, 26 duodenal ulcers).
      Primary eradication was achieved in 35 out of 36 patients (96%). Side effects
      such as dysgeusia and diarrhea were rare and rapidly reversible. We conclude that
      this triple therapy was cost-effective and well tolerated in our study
      population.

PMID- 9289834
TI  - [Conservative treatment of gastroduodenal peptic ulcer perforations: indications
      and results].
AB  - Surgery is the conventional form of treatment for perforated peptic ulcer.
      Conservative treatment has however been described, and is still used in rare
      situations. The present study analyzes the indications and results of
      conservative therapy in our hospital. Between 1978 and 1995, 332 patients were
      admitted for perforated peptic ulcer. Twelve (3.5%), with a mean age of 85 (67
      93) years, underwent conservative treatment (gastric suction, H2-blockers and
      broad-spectrum antibiotics). The diagnosis was established on the basis of
      epigastric pain and the finding of a pleuriperitoneum on the plain film of the
      abdomen. The indication for conservative treatment was a prohibitive
      anesthesiological risk in 11 patients and absence of peritoneal sign in one. The
      evolution was favourable only in 4 patients, who were discharged after a median
      stay of 18 days. Mortality was 8/12 patients. In one of these, autopsy showed
      ischemic colonic perforation. Conservative treatment of perforated peptic ulcer
      is associated with very high mortality. The results suggest that frequent and
      careful clinical monitoring is essential during the first 24 hours. In the event
      of deterioration, surgery must be reconsidered. In addition, the diagnosis should
      be confirmed by ruling out perforation of another abdominal organ.

PMID- 9289836
TI  - [Laparoscopic colon surgery in the regional hospital: initial experiences after
      65 interventions].
AB  - 321 colorectal operations have been performed in our institution in a 4-year
      period from 1992 to 1996. They included 65 laparoscopic interventions for benign
      disease or for palliative treatment of malignancy. 40 patients underwent low
      anterior resections, mostly for diverticular disease. 11 right hemicolectomies, 3
      left hemicolectomies, 1 total colectomy and 7 rectopexies (6 with sigmoid
      resection) were performed. 3 patients with advanced malignant disease underwent
      colostomy. There was a conversion rate of 26%, largely due to adhesions or
      unclear anatomy, decreasing with increasing experience. One trokar-injury of a
      major vessel required immediate conversion to laparotomy. 2 reoperations were
      performed, for an anastomotic leakage after low anterior resection and an
      incarcerated port-site-hernia respectively. A rather high rate of wound
      infections (27%) was reduced to 15% by modifying the technique for retrieval of
      the specimen. The median postoperative hospital stay was 11.6 days. The trend
      towards shorter hospital stay and recovery should not result in uncritical use of
      laparoscopy in colon surgery, in an attempt to meet the rising demand for less
      postoperative pain and shorter hospital stay. This criticism mainly applies to
      tumor surgery, where laparoscopic procedures are indicated in our institution
      only for palliative treatment.

PMID- 9289835
TI  - [Carcinoid tumor in Meckel's diverticulum: case presentation and review of the
      literature].
AB  - Meckel's diverticulum is the most common anomaly of the gastrointestinal tract.
      Neoplasms are extremely rare. We report a case of carcinoid tumor of Meckel's
      diverticulum in a patient with acute abdominal pain. So far, 111 cases have been
      reported. Review of the literature reveals that carcinoids are the most common
      malignant tumors of Meckel's diverticulum. Two thirds of the patients remain
      asymptomatic. Metastases are seen in 25% at diagnosis. The probability of
      metastases depends on the size of the primary tumor. Because of the early
      metastases rate even in small tumors, aggressive surgical management is
      justified.

PMID- 9289837
TI  - [Liver transplantation at the Bern Island Hospital: results from the last 5
      years].
AB  - Today, orthotopic liver transplantation (OLT) is the treatment of choice for the
      endstage of various liver diseases, a 1-year survival rate of 80% and a 5-year
      survival rate of 70% in elective patients without tumor is reported in
      international surveys. The liver transplant program of the Inselspital Bern is
      very small compared with international centers, and this may raise questions
      about the (long-term) results and the justification for such a program. During
      the last 63 months, 59 liver transplantations (including two retransplants) have
      been performed in 57 patients at the Inselspital. The 30-day mortality was 3.5%
      and the 2.5-year overall survival rate was 82% and 93% for elective cases without
      tumor. After a median follow-up of 29 months, 67% of all patients were
      reintegrated fully or part-time in their profession and 81% were independent of
      others' help. We conclude that even a small liver transplant program based on
      routine resources only can achieve results which are comparable to international
      standards.

PMID- 9289838
TI  - [Orthotopic liver transplantation for familial Portuguese amyloidosis].
AB  - Type I familial amyloid polyneuropathy (FAP), or Andrade's disease, is an
      inherited autosomal dominant disease, always fatal, involving mixed progressive
      polyneuropathy associated with systemic amyloid deposits. The disease is
      secondary to mutations of a gene (located on chromosome 18) which encodes for a
      serum protein, transthyretin. This variant protein is essentially (> 90%)
      produced in the liver and constitutes the biological marker of the disease. Many
      surgical teams have established a liver transplantation program for this non
      cirrhotic pathology. Between January and August 1994, we performed three
      orthotopic liver transplantations (OLT) in patients with FAP. The patients were
      men aged between 30 and 33 years and the mean duration of symptoms was 3 years.
      The diagnosis of FAP was confirmed by rectal biopsy and detection of the genetic
      mutation (PCR analysis). All patients presented a severe sensory, motor and
      autonomic neuropathy with major digestive and urologic dysfunction. Two other
      patients were not accepted for OLT because of advanced disease with ulcerous
      lesions of the inferior limbs and cardiopathy. All patients survived with
      excellent post-operative hepatic function. One month after OLT, one patient had
      hepatocellular rejection which responded favorably to steroids. Another patient
      developed post-transfusional B hepatitis 10 months after the graft, but without
      major hepatic lesions. In the three cases, we observed stabilization of the
      peripheral neuropathy and an objective improvement of the autonomic affection
      (neurogenic bladder, diarrhea). The patients who did not undergo transplantation
      died within a year. Thus, in patients suffering from familial amyloid
      polyneuropathy OLT must be performed, especially in the early stage of the
      disease and especially in young patients before serious neurological
      complications set in.

PMID- 9289839
TI  - [Islands of Langerhans autotransplantation after pancreatic resection for benign
      pathology].
AB  - One way to prevent the occurrence of insulin-dependent diabetes after major
      pancreatic resection is to perform islet of Langerhans autotransplantation. Thus
      far, we have performed nine autotransplantations. The last three
      autotransplantations were performed in patients with benign tumoral pathology
      (one corporeal mucinous cyst, one isthmic insulinoma and one corporeal
      cystadenoma). In these three cases, we performed a distal 40%, 75% and 80%
      pancreatectomy respectively, since enucleation was not indicated or not feasible.
      After resection and removal of the tumoral lesion, pancreatic segments were
      injected intraductally with collagenase and digested according to a modified semi
      automated Ricordi's technique. We obtained 105,000, 415,000 and 144,300 non
      purified islets which were then embolized into the liver by intraportal injection
      during the same operative procedure. After surgery, all patients were insulin
      independent. There was no morbidity or mortality. In a patient who presented
      acute pancreatitis of the residual pancreas five months after transplantation,
      insulin therapy was introduced. More than one year after the graft, the two other
      patients remain insulin-independent. In conclusion, we propose islet
      autotransplantation after pancreatic resection for benign focal pathology, to
      prevent or delay the occurrence of insulin-dependent diabetes.

PMID- 9289840
TI  - [Small intestine graft in Switzerland: indications and potential recipients].
AB  - Small bowel transplantation is theoretically the best treatment for patients with
      short bowel syndrome and receiving total parenteral nutrition (TPN). The aim of
      our study was to determine the number of potential candidates for small bowel
      transplantation in Switzerland. We analyzed the clinical parameters of patients
      treated by TPN for short bowel syndrome obtained from university pediatric
      clinics, the SVK (Schweizerischer Verband fur Gemeinschaftsaufgaben der
      Krankenkassen) and referring physicians. In 1995, 7 adults and 2 children were
      under TPN for short bowel syndrome. In the adult group (mean age 57), the causes
      of short bowel syndrome were 3 cases of mesenteric infarct, 2 cases of mechanical
      ileus, one Gardner syndrome and one inflammatory bowel disease. In the pediatric
      group, the causes of intestinal insufficiency were in one chronic enteropathy
      with malabsorption and in one congenital malformation. The average duration of
      TPN was 4.4 (1-10) years for the adults and 13 months for the children. The
      various complications related to TPN were repeated catheter sepsis in 5 patients,
      2 cases of catheter thrombotic occlusion and 3 cases of cholestatic hepatopathy.
      The contraindications to small bowel transplantation were age, a history of
      malignant tumor, pulmonary hypertension and a psychiatric disorder. 4 patients
      were considered potential candidates for transplantation: 2 adults and 2
      children, corresponding to an incidence of 0.5/million inhabitants. Considering
      that the prevalence and incidence of short bowel syndrome in Switzerland are
      comparable to those in other western countries, we think it should be possible to
      initiate a small bowel transplantation program in Switzerland.

PMID- 9289841
TI  - [Clostridium difficile associated diarrhea in cephalosporin administration:
      experiences of the Swiss Adverse Drug Reaction Reporting System 1981-1995].
AB  - 20-25% of antibiotics-associated diarrhea cases are caused by infection with
      toxin-producing Clostridium difficile. Since the advent of broad-spectrum
      antibiotics Clostridium difficile-associated diarrhea has been observed both in
      ambulatory practice and as a nosocomial infection in medical and nursing
      institutions. Clindamycin, aminopenicillins, and cephalosporines are by far the
      most common triggers for this infection. We reviewed all cases of Clostridium
      difficile-associated diarrhea due to cephalosporines which were reported to the
      Swiss Drug Monitoring Center (SANZ) between 1981 and 1995. 87 cases were reported
      (0.9% of 9720 spontaneous reports in this period), 69 (79%) of which were
      considered to be due to cephalosporines. In 74% of the cases the indication for
      the antibiotic treatment was an upper respiratory tract infection. 61 patients
      received cephalosporines by oral route and 9 patients by intravenous route. Two
      patients had to be hospitalized. There were no deaths. The pathogenesis, clinical
      picture, and therapy of Clostridium difficile-associated diarrhea is discussed.
      We conclude from these cases in the spontaneous reporting system of SANZ that
      Clostridium difficile infection due to cephalosporines is a frequent occurrence.
      Because the course can be severe, cephalosporines should be used restrictively.

PMID- 9289842
TI  - [Symptomatic therapy of severe diarrhea in eosinophilic gastroenteritis with the
      somatostatin analog octreotide (Sandostatin)].
AB  - We describe a patient with eosinophilic gastroenteritis whose symptoms included
      severe watery diarrhea (1.5 l/d), abdominal cramps, and weight loss. Biopsies
      revealed massive eosinophilic inflammation of the entire gastrointestinal tract.
      The total plasma eosinophilic count was elevated by up to 30%. Infectious
      etiologies and chronic inflammatory bowel disease had been ruled out. By use of
      the somatostatin analogue octreotide the diarrhea decreased immediately in a dose
      dependent fashion and the patient recovered within twelve days. In this case
      octreotide was helpful in controlling severe diarrhea and limiting the subsequent
      necessary i.v. fluid replacement.

PMID- 9289843
TI  - Neandertal genetics.

PMID- 9289844
TI  - Neandertal genetics.

PMID- 9289845
TI  - Mouse engineering.

PMID- 9289847
TI  - Primordial soup researchers gather at watering hole.

PMID- 9289846
TI  - A bitter battle over insulin gene.

PMID- 9289848
TI  - Novel campaign to test live HIV vaccine.

PMID- 9289850
TI  - NGF signals ride a trolley to nucleus.

PMID- 9289849
TI  - DNA ventures into the world of designer materials.

PMID- 9289851
TI  - Biological information processing: bits of progress.

PMID- 9289853
TI  - Reactions to managed health care.

PMID- 9289852
TI  - No such correspondence.

PMID- 9289855
TI  - Consensus document -- allergic rhinitis in South Africa.

PMID- 9289854
TI  - Reactions to managed health care.

PMID- 9289856
TI  - [An interdisciplinary consensus conference on the diagnosis and therapy of
      testicular tumors].
AB  - In 1988 the German testicular working group was set up by leading experts in the
      fields of urology, medical and radio-oncology. Since then, the working group has
      initiated several clinical studies and conferences with the aim of defining
      current standards in the treatment of testicular germ cell tumours. After a
      series of preliminary joint meetings with representatives from the AUO, AIO and
      ARO of the "Deutsche Krebsgesellschaft", a conference was held in May 1996 to
      agree on a consensus in diagnosis and treatment of testicular germ cell tumours.
      The standards which have been agreed on at the conference refer to the current
      international literature and provide recommendations for the majority of clinical
      situations. Treatment strategies differing from these standards should not be
      chosen except for well argued individual settings or patients treated in clinical
      trials. No consensus could be reached for nonseminomatous stage I, IIA and IIB
      tumours. As a consequence, the differing treatment strategies for these stages
      are summarized in this paper. A subsequent conference in later years is needed to
      possibly find an agreement for these tumour stages and to update the current
      standards according to new clinical experience and knowledge.

PMID- 9289857
TI  - [The demonstration of the radiation-induced production of tumor necrosis factor
      alpha in Ewing's sarcoma RM 82 in vitro and in vivo].
AB  - AIM: The expression of cytokines plays an important role in the transmission of
      the effects of ionizing radiation to tumor cells and normal tissue. Tumor
      necrosis factor alpha (TNF alpha), a pleiotropic monokine, is of special interest
      because of its cytotoxic effect on tumor cells and the induction of hemorrhagic
      necrosis in tumors. We examined the influence of ionizing radiation on TNF alpha
      production in a human Ewing's sarcoma cell line in vitro and in vivo. METHODS:
      The protein and mRNA levels of the Ewing's sarcoma cell line RM 82 were examined
      in vitro with "Enhanced Amplified Sensitivity Immunoassay" (EASIA) and
      semiquantitative RT-PCR before and after treatment with single doses of 2 to 40
      Gy, 1 to 72 hours after irradiation. After successful transplantation to nude
      mice, the time and dose correlation of TNF alpha mRNA production was examined in
      vivo. RESULTS: In vitro, RM 82 had a basal protein level of TNF alpha of 20.1 +/-
      4.3 pg/ml/10(6) cells. We observed a time- and dose-dependent increase of TNF
      alpha expression with a maximum of 125 pg/ml/10(6) (5.9 fold) 24 hours after
      irradiation with 20 Gy. At the mRNA level, the maximal up-regulation occurred 6
      to 12 hours after 10 Gy. In vivo, the xenograft tumor maintained the capacity of
      TNF alpha expression. Time- and dose-dependency in mRNA production showed a
      maximum increase 6 hours after treatment with 10 Gy. CONCLUSIONS: The presented
      experiments show in vitro a dose- and time-dependent up-regulation of TNF alpha
      in the Ewing's sarcoma cell line RM 82 on protein and mRNA level. For the first
      time this phenomenon was also observed in vivo in a human xenograft tumor. This
      tumor model could be used for further experiments to examine the role of TNF
      alpha as a biologic radiation response modifier in human tumors.

PMID- 9289859
TI  - [Which factors modify the reproducibility of patient positioning in the daily
      irradiation routine?].
AB  - AIM: Factors which influence the accuracy of the field application during daily
      irradiation routine are not well known. The aim of this prospective analysis was
      to determine the significance of these factors on the occurrence of field
      misadjustments in irradiation without immobilization and to evaluate their
      clinical relevance. PATIENTS AND METHODS: Fifty-three patients received external
      cobalt-60 beam irradiation without fixation. Once weekly portal images of all
      treatment fields were carried out. In addition to objective patient data (age,
      weight, height, general condition, irradiation indication), the psychological
      situation of the patient during treatment (anxiety, restlessness, pain) and work
      circumstances of the medical staff during treatment were evaluated once weekly.
      The distance of clearly visible anatomic structures to the field borders of the
      portal images were measured and the deviation to the corresponding simulator
      images was calculated. Patient data were correlated to the number of field
      misadjustments (deviation larger than 1 cm). RESULTS: Patients whose condition is
      generally poor and patients being treated palliatively, patients with feeling of
      anxiety, restlessness or pain during simulation or irradiation and heavy patients
      (90 kg and more) were more often misadjusted. The number of field misadjustments
      increased with the stress of the medical staff. CONCLUSIONS: The problem of
      reproducibility of external beam irradiation without fixation in palliative
      treatment is of clinical relevance. Effective analgesic therapy and a comfortable
      and painfree patient set-up reduce misadjustments. In curative treatment,
      immobilization techniques should be used.

PMID- 9289858
TI  - [The acute toxicity of the simultaneous radiochemotherapy of rectal carcinoma].
AB  - AIM: We retrospectively examined the acute toxicity of (neo-)adjuvant combined
      treatment for rectal cancer in an attempt to evaluate potential factors that
      influence the severity of toxic side effects. PATIENTS AND METHOD: Between 1987
      and 1995, 120 patients with rectal cancer (73 patients with primary tumor, 47
      with recurrent disease) received chemoradiation for rectal cancer. Fifty-six
      patients received preoperative chemoradiation, 64 patients were treated
      postoperatively. Radiation was given by 4-field box technique with 6 to 10 MV
      photons. Daily fraction size was 1.8 Gy, total dose 50.4 Gy (range: 41.4 to 56
      Gy) +/- 5.4 Gy (range: 3.6 to 19.8 Gy) local boost in selected cases, specified
      to the ICRU reference point. During the first and fifth week of radiation 5-FU at
      a dose of 1000 m2/d for 120 hours was administered by continuous infusion.
      Toxicity was recorded following (modified) WHO-criteria. RESULTS: Acute grade 3
      toxicity occurred mainly as diarrhea (33%), perineal skin reaction (37%), and
      leukopenia (10%). Extension of the treatment volume including paraaortic lymph
      nodes (L3) led to a significant increase of grade 3-diarrhea (68% vs. 25%, p =
      0.0003) and grade 3-leukopenia (18% vs. 8%, p = 0.03). After abdominoperineal
      resection less patients suffered from grade 3-diarrhea (8% vs. 47% after
      sphincter preserving procedures, p = 0.0006), whereas severe perineal erythema
      occurred more frequently (56% vs. 29%, p = 0.02). Women had significantly more
      toxic side effects (grade 3-diarrhea: 39% vs. 16% in men, p = 0.04; grade 2 to 3
      nausea/emesis: 21% vs. 8% in men, p = 0.018; grade 2 to 3-leukopenia 53% vs. 31%
      in men, p = 0.02). After preoperative chemoradiation a significant reduction of
      grade 3-diarrhea (11% vs 29%, p = 0.03) and grade 3-erythema (16% vs. 41%, p =
      0.04) was noted. CONCLUSION: Treatment volume, type of surgery, sex and sequence
      of treatment modalities are the most important factors that influence the
      severity of toxic side effects. Individual adjustment of 5-FU dosage by
      monitoring its systemic clearance (which is lower in women) could help to avoid
      toxic side effects. The reduced acute toxicity of the preoperative approach
      provides a further argument in favor of the neoadjuvant chemoradiation for rectal
      cancer.

PMID- 9289861
TI  - [Gene therapy with wild-type p53 in lung tumors].

PMID- 9289860
TI  - [Volume changes to the neck lymph node metastases in head-neck tumors. The
      evaluation of radiotherapeutic treatment success].
AB  - AIM: This work is engaged with the volume change of neck lymph node metastasis of
      malignant tumors in the head-neck region during radiotherapy. PATIENTS AND
      METHOD: In 54 patients with head and neck tumors, the volume of neck lymph nodes
      before and after radiation was measured. The volumetry was done with CT
      planimetry. The total dose was 66 Gy (2 Gy/d) telecobalt from 2 lateral opponated
      fields. The time of volume change could be defined with measuring of the half
      time and the doubling-time by the help of Schwartz formula. RESULTS: After 10 Gy
      the volume diminution was about 20% and half-time 24 to 26 days. Afterwards the
      time of volume diminution picked up speed and finally achieved 60 to 72%.
      Meanwhile the half-time decreased to the half value. The result was independent
      of the site of primary tumor, the patient's sex and age. CONCLUSION: In our
      opinion the effectivity of radiotherapy can best be judged with defining of the
      volume change of lymph nodes of the neck.

PMID- 9289862
TI  - [In cervical carcinoma pelvic tumor control improves the cure rate. Can the
      benefit of irradiation without a randomized study be proved?].

PMID- 9289864
TI  - Radiotherapy is a necessary adjuvant in the treatment of early breast cancer.

PMID- 9289863
TI  - [The resection of single brain metastases before whole-brain irradiation].

PMID- 9289865
TI  - [Functional disability in the elderly: epidemiologic aspects].
AB  - The improvements in life expectancy have resulted in an increasing number of
      people at older ages with specific medical problems. The "epidemiologic
      transition" from acute to chronic diseases makes it imperative to change the
      focus from the treatment of different acute diseases to a broader approach. As a
      greater proportion of the population survives to very old ages, the public health
      impact of the burden of disease and disability and related utilization of medical
      care and need for supportive and long-term care has become an important concern.
      This requires a specific approach emphasizing the functional well-being of older
      persons. Recent studies have shown that age and frailty are no synonyms and even
      a greater proportion of the oldest old have a potential for improving. Therefore,
      it is necessary to address this perspective in the medical care of elderly
      people.

PMID- 9289866
TI  - [The preventive home visit--possibilities for geriatric preventive care].
AB  - The major goals of preventive care in the elderly is not to prolong life, but to
      optimize quality of life, to preserve independence and to prevent the onset of
      disability. Not only the disease itself, but also extra- and intra-individual
      risk factors play an outstanding role in the process of disablement. Prevention
      in old age consists of identification and modification of these risk factors.
      Studies have shown that preventive in-home visits with annual geriatric
      assessments can result in reduced nursing home stay and improved functional
      status. This article summarizes the practical approach for conducting preventive
      in-home visits with multidimensional geriatric assessments.

PMID- 9289867
TI  - [Patient assessment in suspected dementia].
AB  - In the near future the number of patients suffering from cognitive impairment and
      senile dementia will increase because of the change in the structure of
      population. General practitioners and specialists will be confronted with this
      problem. The early and differential diagnosis of senile dementia is still a
      problem. Corresponding with the diagnostic algorithms of ICD 10 and DSM IV the
      diagnostic procedure is discussed with geriatric, neuro/psychiatric,
      psychological and psychosocial aspects. The diagnosis also relies on history
      obtained from family and friends. Although cognitive loss is considered a core
      symptom of senile dementia, loss of behavioral disinhibition, loss of functional
      autonomy and mood problems are considered as more important by clinicians and
      family and are of great diagnostic value. Psychometric tests are important but
      they are only one out of many different possibilities to find the right
      diagnosis. If it is possible different specialists should examine the patient.
      Out of the different methods and views of the specialists a comprehensive image
      of the patient takes shape and allows a better understanding of dementia.

PMID- 9289869
TI  - [Assessment of the quality of life].
AB  - Assessment of quality of life (qol) is becoming increasingly important,
      particularly as an outcome variable in assessing the impact of disease, illness
      and treatment. However, considerable problems exists in formulation, measurement
      and interpretation of qol. There is as yet no agreed-upon definition of qol nor
      is there a gold standard measure what complicates the selection of an appropriate
      assessment scale. The various aspects for the selection of a scale are described.

PMID- 9289868
TI  - [Significance of impartial assessment of geriatric brain diseases].
AB  - In addition to traditional psychodiagnostic and neuropsychological methods used
      for assessing cognitive performance and its possible deterioration in the
      elderly, a number of instruments are available today that allow reliable and
      valid behavioural assessments to be made of geriatric patients' everyday
      behaviour. While rating of institutionalized geriatric patients usually focuses
      on the type and amount of nursing care needed, other areas of behaviour, such as
      activities of daily life (ADL) and instrumental ADL (IADL), memory, mood, social
      behaviour and disturbing behaviours are of primary interest in the case of aged
      individuals living in their own homes. The NOSGER (Nurses' observation scale for
      geriatric patients), which was introduced a few years ago, allows assessment of
      six important dimensions of behaviour; the scale can be easily and reliably used
      by professional nursing personnel as well as by untrained caregivers. The present
      paper describes the practical use of the instrument as well as possible graphic
      display of NOSGER findings; furthermore, normative values for five out of six
      NOSGER dimensions are given.

PMID- 9289870
TI  - [Emotionality, age and aging--research perspectives, methodological approaches
      and empirical results].
AB  - The topic of emotionality can be regarded as a frame of reference for different
      perspectives in psycho-gerontological research. In the first chapter five facets
      of the meaning of emotionality are distinguished: emotionality as a trait,
      emotionality as an attribute describing actual subjective experiences,
      emotionality as an attribute describing coping with (stressful) experiences and
      life events or as a consequence of coping activity, emotionality as a result of
      self-regulating processes and as an attribute describing feelings of subjective
      well-being in old age. In a further step methodological approaches for these
      different facets of meaning are described. In the third chapter empirical results
      of three research questions are reviewed: How do people perceive old age and how
      do they perceive the process of aging? Do well developed or regressive coping
      techniques become more important in old age? Which dimensions of personality are
      the best predictors of life satisfaction and perceptions of the process of aging?
      Results of our own research on two specific aspects of emotionality in old age
      are described in detail in the last part of this contribution: How do sensations
      of pain and limits of independent living in old age influence life satisfaction
      and perceptions of the process of aging? How do Jewish extermination camp
      survivors cope with the increasing reminiscence of holocaust-traumatization?

PMID- 9289871
TI  - [Goals in rehabilitation: assessment and outcome evaluation].
AB  - Major aims of rehabilitation in geriatrics are related to the ICIDH
      classification. Therefore, scales of functional competence and measures of
      handicap are predominantly used for outcome measurements, the Barthel-Index, for
      example. Further important aims and criteria are reductions in the demand of
      nursing care and institutionalized care. Studies of the impact of geriatric
      rehabilitation on quality of life are still lacking.

PMID- 9289872
TI  - [Assessment of chronic pain in elderly patients].
AB  - Pain is extremely common among older people but often inadequately treated.
      Chronic pain and its management have major implications for quality of life and
      quality of care, especially for terminal ill patients and residents of long-term
      care facilities. Many physicians lack information about pain assessment and may
      have an inaccurate knowledge base about pharmacological agents and non
      pharmacological approaches used in pain control. Although fundamental data on the
      pathophysiology and management of chronic pain is still lacking there is some
      information to provide a framework for rational nosology and therapeutic
      strategy. Some guidelines may help to improve pain assessment and management in
      elderly people and may help to enhance physicians' awareness about that problem.

PMID- 9289873
TI  - [Malnutrition in the elderly: the Mini Nutritional Assessment (MNA)].
AB  - Frail elderly in the community, in nursing homes or in hospitals are at increased
      risk of malnutrition. In many instances, their existing nutritional disorders go
      unrecognised and adversely affect their health, ability to overcome disease, and
      so is associated with poor clinical outcome. The prevalence of malnutrition
      ranges from 5-10% in free-living elderly to 30-85% in homebound, nursing home,
      and hospitalised elderly. Possibilities exist to prevent or correct this
      malnutrition, but have not been frequently used until now due to the lack of a
      specific validated tool to screen for malnutrition. The goal of the Mini
      Nutritional Assessment (MNA) is to determine who is at risk of malnutrition, and
      hence to permit early nutritional intervention. It has been designed for easy use
      by general practitioners as well as health professionals involved in admitting
      patients to hospitals and nursing homes. The test, which comprises simple
      measurements and a brief questionnaire, can be performed in about 10 minutes. It
      involves: anthropometric assessment (weight, height and weight loss) general
      assessment (lifestyle, medication and mobility) dietary assessment (number of
      meals, food and fluid intake, autonomy of eating self assessment (self-perception
      of health and nutrition). The MNA has now been validated in three studies
      involving more than 600 elderly individuals, from the very frail to the very
      active in free-living and long-term care environments. The MNA was validated
      against a clinical evaluation and a comprehensive nutritional assessment. It can
      classify the elderly as well-nourished, undernourished, or at risk of
      malnutrition. The MNA can be an important tool in evaluating the risk of
      malnutrition in the elderly, if integrated into geriatric assessment programs.

PMID- 9289875
TI  - [Social competence and ability to make decisions].
AB  - Social competence and judgement can be separated in a somatic and in a mental
      competence. In mental competence, the capacity to consent has to be distinguished
      from the capacity to judge legal or more complex matters. Autonomy of patients
      requests that the capacity of consent is given, even in the presence of
      considerable cognitive impairment. On the other hand, competence in legal matters
      may be not any longer given in the presence of light to moderate cognitive
      impairment. In the assessment of competence, it is important that the person has
      the ability to make a choice, the ability to give directives, and the ability to
      do for oneself. Cognitively impaired patients therefore require assistance and
      protection in legal matters already at an early stage of the disease.

PMID- 9289874
TI  - [Assessment of need for nursing care].
AB  - The ideal prerequisites for the evaluation of care needs in geriatric patients
      are mainly four: First a comprehensive assessment of the status of the geriatric
      patient. Second the existence of procedural standards. Third the existence of
      consensus about what quality standards in geriatric medicine could be and fourth
      a resource allocation system that gives some confidence in its capacity to set
      clinically sound incentives and its intention to guarantee quality and equity.
      Because of the fact, that the author is convinced that the US (Omnibus Budget
      Reconciliation Act (OBRA-87) mandated Minimum Data Set (MDS) for nursing homes
      with the connected Resident Assessment Instrument (RAI) meets some of these
      criterias, this system and the Resource Utilisation Groups (RUGs) case-mix
      methodology which is based on MDS data is described.

PMID- 9289876
TI  - [Problems of laparoscopy using captoperitoneum: controlled ventilation,
      circulation, blood gas and body temperature].
AB  - More and more veterinarians are going to perform laparoscopic diagnosis and
      surgery those days. But the technique using capnoperitoneum implicates several
      alterations of different physiological parameters, which, without proper
      monitoring, are often realized to late. Pathophysiology under CO2 insufflated
      abdomen as well as counter measures to keep or reestablish physiological
      situations are described. Within experimental studies, 27 pigs received partial
      colon resection using the laparoscopic technique, another six after laparotomy.
      They were compared concerning controlled ventilation, cardiovascular and blood
      gas parameters as well as the body temperature. Monitoring of the end-exspiratory
      CO2-gas tension as well as controlled ventilation seems to be essential. Blood
      gas analyses are proposed additionally. Under the described laparoscopic
      conditions blood circulation and body temperature seem to be influenced
      positively.

PMID- 9289877
TI  - [Case report. Two pregnant cows of the bright red German thoroughbred strain].

PMID- 9289878
TI  - [Contribution to the treatment of acute bovine mastitis with cefquinome].
AB  - Cefquinome is the first 4th generation cephalosporin antibiotic developed for use
      in veterinary medicine. A European multicentre study established a high in vitro
      activity for this modern antimicrobial drug against a wide spectrum of bovine
      pathogens. Gram-positive and gram-negative mastitis agents were inactivated even
      at very low active ingredient concentrations, including Enterobacteriaceae which
      are often resistant to other drugs. The results of clinical trials using
      experimental E. coli mastitis as an example demonstrate the efficacy of
      cefquinome in vivo. Parenteral administration at a dose rate of 1 mg/kg body
      weight when compared with conventional therapy using a control drug with equally
      good in vitro activity, produced significantly better therapeutic results.

PMID- 9289879
TI  - [Critical comparison of rectal and ultrasonographic results of ovarian conditions
      in the interestrus of cattle].
AB  - 41 heifers of 260-440 kg body weight used in an experiment were polyovulated with
      PGF2 alpha and PMSG (1000 IU). Animals were slaughtered during luteal phase of
      ovarian cycle (day 12-15). Shortly before slaughter ovarian structures were
      defined by rectal palpation und ultrasonographical examination. Post mortem
      ovaries were collected to compare their structures with previously performed in
      vivo diagnosis. More follicular structures were detected sonographically (109%)
      than could be found by morphologic examination (100%). Concerning corpora lutea a
      right diagnosis was made by palpation in 94% of cases, whereas the rate was only
      85% for ultrasonographical examination. Main reasons for false diagnoses of
      ultrasonographical examination are as follows: multiple ovarian structures,
      corpora lutea with holes inside, atypical shape of ovaries, atypical
      ultrasonographical pictures and irregular shape of follicles.

PMID- 9289880
TI  - [Real-time ultrasonographic pregnancy diagnosis (B-mode) in sheep. 3.
      Determination of the number of embryos and fetuses].
AB  - Transrectal ultrasound examination was performed once in 1159 German Mutton
      Merino ewes in a standing position using a 5.0 MHz linear array transducer (group
      1), 505 German Mutton Merino ewes were restrained in dorsal recumbency while
      scanned transrectally using a 7.5 MHz probe (group 2). Referring to actual number
      of lambs born the prepartal prediction of fetal number was correct in 71.8%
      (group 1) and 78.6% (group 2) of the ewes from days 17 to 69 p.c. The highest
      accuracy for determining fetal number (89.1%) was in group 1 at days 35 to 46 of
      gestation. In group 2 the accuracy was more consistent over the whole period of
      examinations and reached over 80% from as early as 29 days p.c. As litter size
      increased, examinations in both groups became increasingly inaccurate in
      determining correct litter size. A subdivision of living, underdeveloped and dead
      embryos or foetuses was possible by the presence or the absence of a heartbeat
      and the crown-rump-length of the embryos or foetuses. The percentage of ewes with
      embryonic or fetal loss is given.

PMID- 9289881
TI  - [Examination of primary SPF swine after experimental infection with Haemophilus
      parasuis. Clinical symptoms, changes in hematological parameters and in the
      parameters of the cerebrospinal fluid].
AB  - The objectives of this work were to cause the Glasser's disease (GD) in primary
      specific pathogen free piglets after experimental infection, to observe the
      clinical symptoms and to examine the influence of the infection on the
      haematological parameters. GD was caused by experimental infection of Haemophilus
      parasuis in seven to eight weeks old specific pathogen free piglets. In relation
      to the infection route the morbidity was high (83-100%) and 20% of the infected
      piglets died. Based on the physical examination fever, respiratory distress,
      cramps and paralysis were observed which are typical for GD. Arthritis and nerval
      symptoms are also typical but less common in Glasser's disease. PCV was
      significantly decreased and WBC significant increased before the piglets were
      euthanatized.

PMID- 9289882
TI  - [Behavior dissorders in psittacines. 1. Symptoms and causes].
AB  - Psittacines embody in an ideal fashion the child-like characteristics that humans
      adore. Animal lovers are unable to resist their expressive eyes, brightly
      coloured plumage, tameness and mimicry of human speech. The desire of pet-owners
      to have a tame, speaking bird with a very strong bond to its owner is achieved
      through hand-rearing, but this results in psychoreactive behavioural
      abnormalities in these highly social birds due to abnormal fixation. The signs
      and causes of these behavioural abnormalities, also called cage neuroses, are
      explained. The complex of feather-plucking, feather-ingestion and self-mutilation
      is considered in depth, and there are numerous illustrations.

PMID- 9289883
TI  - [Equine motor neuron disease (EMND). A case report].
AB  - A 13-year-old warmblood mare was presented because of progressive weight loss,
      general weakness and trembling. On examination the horse stood with its head
      lowered and the limbs placed under the body. On lifting its head spasms of the
      neck muscles could be observed. At the same time the horse developed trembling
      over the lower neck and muscle fasciculations continued over the whole body.
      Additional signs included frequent recumbency, polyphagia and facial
      hyperaesthesia. The horse showed no signs of ataxia. Haematology was normal.
      Blood biochemistry revealed slight increased aspartate aminotransferase (AST:
      1060 U/I) and creatine kinase levels (CK: 441 U/I). Based on the clinical
      findings equine motor neuron disease was diagnosed. The horse was euthanatized
      due to poor prognosis and the progression of symptoms. The typical
      neurodegenerative changes found on histological examination of the spinal cord
      confirmed the diagnosis.

PMID- 9289884
TI  - [Doping in animal rights law: the responsibility of the veterinary surgeon].
AB  - Unlike the situation in humans, it is illegal to administer doping drugs to
      animals. The Doping Commission of the European Council has defined the term
      doping. According to this definition, the therapeutic use of drugs is not doping.
      The treatment of pain is also therapeutic. However, governing bodies of sport can
      apply stricter regulations (doping lists). It is possible for veterinarians to
      infringe paragraph 3 (11) of the German animal welfare act if they act recklessly
      or without due care, and a prosecution may result. It is therefore obligatory for
      the veterinarian to advise of the possible consequences of administering a drug
      which has a doping effect, or is included on a doping list.

PMID- 9289885
TI  - [Diagnostic and therapeutic aspects of the pyometra-endometritis complex in
      dogs].
AB  - 652 bitches suffering from the pyometra-endometritis complex were divided into
      three groups. General condition and the haemogramm were examined. The bitches of
      group III (n = 220) had greatest disturbances, and the mortality rate was high,
      especially in bitches with uterine rupture (50%). The healing rate of 63.7% in
      this group is the result of a special treatment schedule that is also possible
      under practical conditions.

PMID- 9289886
TI  - [Hepatozoon canis infection of dogs in Germany: case report and epidemiology].
AB  - This paper reports on a case of hepatozoonosis of a dog imported from Italy to
      Germany being additionally infected with Ehrlichia canis and Babesia canis.
      Furthermore, a survey of the epidemiology of the Hepatozoon canis infection is
      presented.

PMID- 9289887
TI  - [Results of bacteriologic and mycologic investigations of otitis media in dogs].
AB  - This study describes the bacteriological and mycological investigation of 212 ear
      swab samples of dogs with an otitis externa. 11 samples were sterile. Malassezia
      pachydermatis could be cultivated in 72.1% of all samples, in 21.9% of these
      cases in pure culture. In 27.9% of all samples only bacteria were found.
      Coagulase-positive haemolytic Staphylococcus and Malassezia pachydermatis were
      isolated together in 31.8% of all ear swab samples. Pseudomonas aeruginosa could
      be detected in 22.9%, haemolytic Streptococcus in 8.0%. The evaluation of
      antibiograms showed little resistance of staphylococcus to most common
      antibiotics or chemotherapeutics respectively, but the growth of Pseudomonas
      aeruginosa and especially Proteus spec. was only inhibited by a few substances.

PMID- 9289889
TI  - [Observations on epidural anesthesia in cats from the anatomical viewpoint].
AB  - The topographic-anatomical situation of the conus medullaris and the cauda equina
      in cats is shown: in about two thirds of the cases the conus medullaris at least
      reaches the level of the first sacral vertebra. As far as the site of the
      epidural injection is concerned the sacrococcygeal space or the first
      intercoccygeal space are proposed in order to avoid damage to the spinal cord.
      When seeking the site of injection it is advantageous to orientate oneself by
      following the sacral processus spinosi in caudal direction beginning with the
      lumbosacral space. In case of adipose animals the first intercoccygeal space can
      be palpated by moving the tail up and down. Both sites are equivalent. The volume
      to be injected varies between 0.3 and 0.9 ml solution per cat depending on the
      needs.

PMID- 9289888
TI  - [Placebo-controlled double-blind study on the efficacy of a paramunity inducer in
      the treatment of naturally FeLV-infected cats].
AB  - The study involved 120 cats, of which 60 were treated with Baypamun HK and 60
      cats received a preparation of virus free cell culture medium. Therapeutic
      efficacy was determined by monitoring the general status of health, body weight,
      skin, lymph nodes, oral cavity, the presence of the p27 antigen and the FeLV p27
      antigen concentration in serum. No statistically significant differences between
      both groups could be demonstrated neither for clinical nor for virologic
      parameters. Remission of the viremia occurred in 11.7% of the cats treated with
      Baypamun HK and in 6.7% of the cats treated with placebo. The FeLV p27 antigen
      level decreased by an average of 7.2% with Baypamun HK and by an average of 5.1%
      with placebo.

PMID- 9289890
TI  - [Intraocular metastasis of bronchial carcinoma in a cat].
AB  - A rare case of a ten-year-old neutered male Persian cat is described, in which
      metastasis of a pulmonary adenocarcinoma into the choroid of the right eye had
      led to visual impairment and major ophthalmoscopically detectable changes of the
      fundus. These were a generalized hyporeflectivity of the tapetal fundus due to
      retinal edema with multiple areas of retinal detachment and also severe edema of
      the papilla, furthermore an increased tortuosity and congestion of the retinal
      vessels. While the diagnosis of a primary lung tumor could be made intra vitam
      based on the result of an x-ray examination, the neoplastic nature of the fundic
      lesions could only be confirmed by histopathologic examination.

PMID- 9289891
TI  - [Osteosarcoma in cats: epidemiological, clinical and radiological findings in 78
      animals (1990-1995)].
AB  - In this study 78 cats with osteosarcoma were identified from biopsy logs and
      evaluated retrospectively regarding breed, sex, and age distribution, tumor
      location, clinical symptoms, radiographic findings, biologic behavior of the
      neoplasm, and outcome following therapy. There was no significant breed or sex
      prediffection among the cats. The average age was 10.1 years, with a range of
      less than one to over 17 years. 36 (46%) of the osteosarcomas were localized in
      the bones of the limbs, 42 (54%) were found in flat or irregular bones. The hind
      limbs (25 cases) were affected significantly more often than the front limbs (10
      cases). The most prevalent sites were the distal femur, proximal tibia, the
      humerus and the digits. Four of the tumors occurred after osteosynthesis of a
      previous fracture. In most of the cats limb tumors were associated with chronic
      lameness. The skull was the most common site for tumors of the flat and irregular
      bones (35 cases), which involved the oral cavity in 27 cases. The most common
      symptoms were dental problems, deformations of the skull, and nasal discharge.
      The remaining tumors of the flat and irregular bones were located in the pelvis
      (3), vertebrae (2), scapula (1), and rib (1). Radiographic findings were very
      variable and ranged from lytic to purely osteoproliferative forms. With tumors of
      the flat and irregular bones, tumor recurrence was a common cause for euthanasia.
      Animals with tumors of the limbs had a good prognosis following amputation.

PMID- 9289892
TI  - [Gas bubble disease of fish].
AB  - Gas bubble disease (GBD), a non-infectious, environmentally/physically induced
      trauma, is caused by an increase in the dissolved gas pressure above the ambient
      air pressure (supersaturation). Frequently the cause is an increased partial
      pressure of nitrogen-especially in spring-/groundwater. All fish species as well
      as amphibians and aquatic invertebrates are susceptible. Fish species and age
      groups are different sensitive; swim up fry is very endangered. The disease may
      occur in a chronic form at approximately 103% and in an acute form at above
      110/115% total gas pressure (TGP). Fish, especially fry, with the chronic form
      die slowly without symptoms. The clinical symptoms of the acute form are
      disorientation, subcutaneous emphysema, embolism, exophthalmus mostly only on one
      side, swimming near the water surface with darkened skin, haemorrhages and high
      mortality. Losses increase with increased TGP. Generally, mortality in the
      chronic form increases by secondary infections of emphysematous tissue. As
      technical processes may be the cause for an increased total gas pressure, such as
      water pumping, heating water or mixing cold with warm water, in this context we
      could speak from a "technopathy". The following "therapeutic" measurement is
      recommended: avoid causal factors, transfer damaged fish in expanded water, turn
      off the cause, compensate the pressure in deeper water, if possible.

PMID- 9289893
TI  - [Electron microscopy].

PMID- 9289894
TI  - [Prohibition of use of beta agonists in the feed of market animals].

PMID- 9289895
TI  - Proceedings of the 2nd International Congress on Hazardous Waste: Impacts on
      Human and Ecological Health. Atlanta, Georgia, June 5-8, 1995.

PMID- 9289897
TI  - Antisense gene knockdown in the nervous system revisited: optimism for the
      future.

PMID- 9289896
TI  - 12th European Symposium on Animal, Plant and Microbial Toxins. Basel,
      Switzerland, 25-28 August 1996. Abstracts.

PMID- 9289898
TI  - John C. Eccles (1903-1997)

PMID- 9289900
TI  - [Clinical application of X-ray endovascular revascularization of pyelonephritic
      kidney: first experience].
AB  - For compensation of schronic ischemia of the pyelonephritically afflicted kidney,
      the authors first used peripheral venous revascularization. The surgical
      intervention involved X-ray endovascular stenosing of the subsegmental renal
      veins. Local rearrangement of venous circulation provided a better ischemic
      tolerance due to more complete oxygen uptake from the highly oxygenized renal
      venous blood. The results of peripheral venous revascularization were analyzed.
      There were improvements in the clinical presentation of the underlying disease,
      in the filtration and reabsorption of the kidney exposed to operation, and a
      reduction in blood pressure.

PMID- 9289901
TI  - [Contrast-enhanced ultrasound studies in gynecological practice].
AB  - Sixty eight female patients of fertile age (54 with infertility and 14 with
      uterine abnormalities) were examined by sonocontrast hysterosalpingography. The
      results of X-ray contrast hysterosalpingography, sound hysterosalpingian
      hydrotubation, laparoscopic chromotubation, and MRT were compared. Echovist-200
      (Schering, Germany) was used as a contrast agent. Ultrasonography was performed
      under the guidance of a convex vaginal transducer at 6.5 mHz using a Philips P700
      scanner. The findings show the great potentialities and advantages of the
      techniques in evaluating the tubes of the uterus and in diagnosing its diseases.

PMID- 9289899
TI  - [Differential radiation diagnosis of microcalcinates grouped in breast].
AB  - A complex methods was used to examine 39 females with the microcalcinates grouped
      in the breast. The diagnostic efficiency of a number of mammographic and
      sonographic signs was comparatively evaluated. Ultrasonography was shown to be
      advisable in differentially diagnosing cancer and sclerosing adenosis. A
      combination of mammography and sonography may establish an accurate diagnosis in
      78% of cases.

PMID- 9289902
TI  - [Technological problems in use of fast reactors for radiotherapy of patients with
      malignant tumors].
AB  - The authors discuss the technological problems associated with the use of fast
      neutrons in radiotherapy of cancer patients and outline the approaches to the
      solution of these problems. The state of the art is assessed. Physical and
      radiobiological prerequisites for the use of fast reactors for radiotherapy of
      patients with malignant tumors are analyzed. Results of clinical use of BR-10
      reactor at the Medical Radiology Research Center, Russian Academy of Medical
      Sciences, are presented. Experimental and clinical findings indicate that the
      results of radiotherapy may be appreciably improved if a novel perspective source
      of fast neutrons, a nuclear reactor, is used.

PMID- 9289903
TI  - [A case of using PALMAZ-SCHATZ intracoronary stent in patient with nonspecific
      aortoarteritis].

PMID- 9289904
TI  - [A case of tunnelized concrement in ureterocele].

PMID- 9289905
TI  - [Combination of two diseases of knee joint].

PMID- 9289906
TI  - [Technological approaches to total body radiotherapy of cancer patients].

PMID- 9289908
TI  - [Methods of introscopy in diagnosis of diastematomyelia].

PMID- 9289907
TI  - [Differential diagnosis of posterior cranial fossa: potentialities and unsolved
      problems].
AB  - Brain CT was made in 720 patients with tumors of the central nervous system. The
      subtentorial site of the process was encountered in 50.4% of cases. The paper
      outlines the skialogic characteristics of tumors having varying structures:
      medulloblastomas, ependymomas, astrocytomas, angioreticulomas, truncal gliomas,
      metastases, epidermoids, neurinomas, meningiomas, chemodectomas, arteriovenous
      malformations. Difficulties in determining the histostructure of tumors on the
      basis of skialogic manifestations were noted. Anatomic and skialogic approaches
      which may assume the type of neoplasmic process were outlined.

PMID- 9289909
TI  - [Current methods for processing of radiographic medical films].

PMID- 9289910
TI  - [The University of X-ray laboratory Assistants. Lesson 1. Million microns].

PMID- 9289911
TI  - [Routine chest x-ray study in diagnosis of myocardial dysfunction. Part 1].

PMID- 9289913
TI  - [Vitamin status of the population from regions suffering from the accident at the
      Chernobyl power plant, and its correction with multivitamins "Duovit" and
      "Undevit" and multivitamin premix 730/4 of the firm "Roche"].
AB  - There was no differences of principle in vitamin status of population living in
      'zones of strict control' (Brjanskaja, Mogilevskaja, Gomel'skaja regions) and
      Moscow's population. Mean indices of vitamin C, A, E, B1 and carotene status in
      children and adults were not differed in two groups of population. But vitamin B2
      and niacin status in Moscow's adults were worse. Among children from Moscow
      vitamin C deficiency was found more rare and vitamin E deficiency more often than
      those in population from regions suffering from Chernobyl. It was established
      that supplement of third dishes with vitamin C is not sufficient for elimination
      of vitamin C deficiency. Polyvitamin pills 'Duovit' or premix 'Roche' were more
      effective in removal vitamin deficiency.

PMID- 9289912
TI  - [Value of X-ray findings and chronic ischemic heart disease risk factors for
      prognosis of myocardial infarction].
AB  - The results of comprehensive studies of 120 males aged 22-69 years who suffered
      from CHD with angiographic signs of coronary sclerosis were analyzed. The
      findings have indicated that in young patients (aged 22-40 years) X-ray
      cardiometric evidence may long remain in the normal range despite profound
      functional changes in them. Cardiac arrhythmia concurrent with the enlarged heart
      is an important poor predictor of myocardial infarction.

PMID- 9289914
TI  - [Selenium content in wheat and rye flow from Russia, cis nations and Baltic
      countries].
AB  - Selenium concentrations in wheat and rhy flour of Russia and CSC vary from 46 to
      577 mg/kg and from 6 to 87 mg/kg correspondingly. The highest wheat flour
      selenium--300-600 mg/kg--is typical to wheat, imported from USA and Canada. Low
      values of selenium wheat flour (34-64 mg/kg) and of selenium rhy flour (5-20
      mg/kg) from Kaliningrad, Novgorod, Pskov, Leningrad regions, Altay, Byelorussia
      and Baltic countries show the possibility of low selenium consumption by the
      population of these regions. Low selenium is demonstrated for wheat flour
      imported to Kirghizia - 81 +/- 31 mg/kg and produced in north-western part of
      Ukrain: Volinsk, Sumi, Kiev regions--64-78 mg Se/kg. Sakhalin and selenium
      deficient Buryatia utilize predominently imported wheat flour with high selenium
      content - 250-260 mg/kg. Native grain with relatively high selenium is found in
      Kurgan, Orenburg, Lipetsk, Tambov regions, Tataria and Uzbekistan - 160-185
      mg/kg.

PMID- 9289915
TI  - [Enzymatic analysis of the quality of foodstuffs].
AB  - Enzymatic analysis is an independent and separate branch of enzymology and
      analytical chemistry. It has become one of the most important methodologies used
      in food analysis. Enzymatic analysis allows the quick, reliable determination of
      many food ingredients. Often these contents cannot be determined by conventional
      methods, or if methods are available, they are determined only with limited
      accuracy. Today, methods of enzymatic analysis are being increasingly used in the
      investigation of foodstuffs. Enzymatic measurement techniques are used in
      industry, scientific and food inspection laboratories for quality analysis. This
      article describes the requirements of an optimal analytical method: specificity,
      sample preparation, assay performance, precision, sensitivity, time requirement,
      analysis cost, safety of reagents.

PMID- 9289916
TI  - [Evaluation of modern child nutrition in boarding schools in Taimyr].
AB  - The given reference includes an information about a nourishment, an average daily
      nutrient and energetic content of foodstuffs in the menu of students in boarding
      schools on Tajmir. It is determined that there is a disbalance of the main
      components and the fatty acid, mineral, vitamin contents in the menu of the
      children of all the ages. The nourishment of the children living in the condition
      of the Far North has been demonstrated to need correcting.

PMID- 9289917
TI  - [Structure of nutrition of one of Moscow's districts and its relationship to risk
      factors of chronic noninfectious diseases from the standpoint of medical
      prevention].
AB  - Dietary intake was studied in 295 of Moscow's residents by 24-hour recall method.
      High level of animal fat, sugar and cholesterol (Ch) were found in diet of man
      and women. Energy intake of men is higher than that of women at the expense of
      animal fat and protein. Women consume less amount of cholesterol-containing food.
      The levels of serum Ch, HDLP-Ch, triglycerides are in close relation with blood
      pressure values. The levels of serum Ch, HDLP-Ch, systolic and diastolic blood
      pressure are connected with variables of age and body mass index.

PMID- 9289918
TI  - [Therapeutic-prophylactic milk products with a new immunocorrector of natural
      origin].
AB  - Authors had received and investigated on experiment milk medical and prophylactic
      products (milk and kefir) with addition peptide, obtained from nervous tissue of
      squids. It has been established that addition of gangliin to the milk and kefir
      causes stimulation cellular and humoral factors of immunity answer at laboratory
      animals. Medical and prophylactic milk products with gangliin return to the
      normal state reduced immunity indexes of the mice with experimental
      immunodeficits.

PMID- 9289920
TI  - [Structure of the actual nutrition of patients with non-insulin-dependent
      diabetes mellitus in Moscow in 1994-1995].
AB  - Dietary intake with computer conversion was studied in patients with insulin
      dependent diabetes mellitus in Moscow in 1994-1995. It was shown that dietary
      intake of energy from macronutrients and intake of some micronutrient were
      inadequate in these patients.

PMID- 9289921
TI  - [Use of the term "dietary fiber" and its classification].
AB  - Complexity of dietary fiber composition, differences of their chemical structure
      and ratio of components, dependence of composition and properties upon the
      methods of isolation resulted in different definitions of dietary fibers and
      misunderstanding of their nature and role in nutrition. Among different
      definition--dietary fibers, raw fibers, crude fibers, vegetable fibers--the most
      adequate the definition 'dietary fibers'. This definition indicates on fibrous
      nature of main components: celluloses, hemicelluloses, pectines and on their
      significance in nutrition. The term dietary fibers obtains recognition and
      supplements the other synonyms.

PMID- 9289919
TI  - [Clinical and metabolic effects of biological active food additives-
      phospholipids--in patients with cardiovascular diseases].
AB  - Uses of new phospholipid-containing food supplement 'Tonus' in patients with
      ischemic heart disease, hyperlipoproteinemia or hypertension during 4 weeks
      promoted positive changes clinical symptoms of diseases against a background of
      lowering of serum cholesterol, triglycerides and increasing of HDLP-cholesterol
      and improving liver function.

PMID- 9289922
TI  - [Lipid peroxidation and various parameters of mineral metabolism in patients with
      alimentary obesity during therapy with monosodium glutamate].
AB  - Lipid peroxidation and mineral metabolism were studied in patients with III
      degree of obesity and bad standing of sodium restricted diet before and after
      treatment with including in diet of monosodium glutamate (MSG). It was
      established well being of MSG and absence of negative effect on loss of body mass
      in course of dietary treatment. MSG caused normalization of level of diene
      conjugates and some minerals in serum of patients.

PMID- 9289924
TI  - [Fluke invasion and the immune system of the snail].
AB  - This is a review article concerning an influence of trematodes infections on a
      defence system of snails. Changes in: snails' plasma composition, a number of
      hemocytes, size of a hemopoietic organ, molecules secreted by hemocytes and
      defence cells activities caused by the infections are discussed in detail. The
      differences in humoral and cellular response between susceptible and resistant
      strains of snails as well as between young and old snails are also presented in
      the article. Finally, the problem of an existence of the specific immunological
      memory in snails is analyzed.

PMID- 9289923
TI  - [Prof. Dr. Hab. Witold Kasprzak (obituary)].

PMID- 9289925
TI  - [Toxocara canis (Nematoda) and toxocariasis of animals and humans].
AB  - Some aspects of dog toxocarosis and syndrome of visceral larva migrans in human
      toxocarosis, particularly in children were presented. In detail the morphological
      characters and biology of Toxocara canis, its pathogenicity, ways of invasions as
      well as conditions favouring the spreading of parasites were discussed. Attention
      was paid to the efficacy of diagnosis of invasions, treatment and prophylaxis.
      The current toxocarosis threat was analysed and epidemiological prognosis was
      moved forward.

PMID- 9289927
TI  - [The influence of treatment on the course of experimental Fasciola hepatica
      infection and weight gains in sheep].
AB  - The course of Fasciola hepatica infection was studied by the coproscopical
      methods in two farms of Southern Poland. The extensity of infection reached
      between 84 to 94 per cent. The experimental studies has been done on 54 lambs at
      the average weight of 21.50 kg. The lambs were divided in 3 groups with 18 lambs
      in each. In the first group were non-infected animals; second group was infected
      with 200 metacercaria and treated with Fasinex (10 mg/#kg body weight) 6 weeks
      after infection. The third group was infected with 200 metacercaria, but has not
      been treated with Fasinex. The best results were obtained in the first group. In
      this group the weight gain was about 4 kg (14.7 per cent) higher comparing with
      the group third (infected, non-treated) group. The weight gain of group two
      (infected and treated) was 2.42 kg (11.0 per cent) higher as in group third
      group.

PMID- 9289926
TI  - [Use of the ISAGA method in detection of specific IgM, IgA, IgE antibodies in
      acquired and congenital toxoplasmosis].
AB  - Immunocapture assays ISAGA PLUS IgA/IgM (bioMerieux) and IgE ISAGA were used to
      determine their usefulness in the diagnosis of acquired and congenital
      toxoplasmosis. Specific IgM, IgA and IgE antibodies were tested in 134 patients,
      namely pregnant women who seroconverted during gestation (n = 20), children with
      congenital toxoplasmosis (n = 5), patients with toxoplasmic lymphadenitis (n =
      56) and immunocompetent individuals with chronic Toxoplasma gondii infection (n =
      53). Altogether 172 sera were examined. Specific IgM antibodies were detected in
      all sera from pregnant women (100%) with recent T. gondii infection (1-8 weeks
      after seroconversion), in all patients with toxoplasmic lymphadenopathy (1-3
      months after onset of symptoms) and in their control examinations after 2 and 5
      months (100%) and also in 35 (66%) out of 53 patients with chronic infection. In
      infants with congenital toxoplasmosis IgM were found only in one new-born;
      equivocal results were obtained in 3 children during the asymptomatic serological
      reactivation in the second year of life. Specific IgA antibodies were present in
      sera from 15 (75%) out of 20 women seroconverted during pregnancy; in 3 cases the
      results were equivocal. IgA antibodies were detected in sera from 30 (81.1%) out
      of 37 patients with toxoplasmic lymphadenitis examined once; in 19 patients
      examined 3 times IgA antibodies were present in all the cases in the first
      serological examination performed when clinical symptoms were first observed
      (100%), in 17 patients after 2 months (89.5%) and in 11 patients after 5 months
      (57.9%). IgA antibodies were also detected in 21 sera (39.6%) from patients with
      chronic T. gondii infection. In children with congenital toxoplasmosis IgA
      antibodies were found in 3 cases during serological reactivation after
      discontinuation of pyrimethamine-sulfadiazine therapy; in these cases equivocal
      results of IgM antibodies were present, and positive result of IgE antibodies in
      one case. Specific IgE antibodies were detected in sera from 17 (85%) out of 20
      women with seroconversion and in 18 patients with lymphadenopathy (32.1%); in the
      last group IgE antibodies were not present in the follow-up examination after 5
      months. IgE antibodies were detected only in 5 cases (9.4%) with chronic
      infection. IgA and IgE antibodies in ISAGA begin to appear about a week later
      than IgM antibodies: in sera collected between the 2nd and 3rd week after
      invasion the positive results were obtained in all cases (100%). Therefore, ISAGA
      PLUS IgA/IgM (bioMerieux) is useful for the diagnosis of recent T. gondii
      infection especially in women with suspected seroconversion during pregnancy.
      ISAGA PLUS IgA/IgM is more sensitive than any conventional method routinely used
      and so far is a specially efficient technique for newborns and infants suspected
      for congenital infection and/OR IN DIAGNOSING CONGENITAL TOXOPLASMOSIS DURING
      IMMUNOLOGICAL RECRUDESCENCE. tHIS TEST HAS A LIMITED VALUE IN TOXOPLASMOSIS WITH
      LYMPHADENOPATHY BY REASON OF POSSIBILITY OF A LONG PERSISTENCE OF iGm and IgA
      antibodies detected by ISAGA. Detection of specific IgE antibodies using ISAGA
      technique may be useful for differential diagnosis of acute and chronic phase of
      T. gondii infection and also in some cases of serological reactivation of
      congenital toxoplasmosis.

PMID- 9289929
TI  - [Problems with nosematosis in reproduction apiaries].
AB  - Nosemosis is on the list B of International Animal Disease Office. Nosema apis
      was found in Poznan voivodship apiaries. The level of invasion of this parasite
      was 0-40% of investigated colonies in particular apiaries. According to the
      Polish programme only 20% of colonies can be N. apis positive in a honeybee
      breeding apiary. It is suggested that the minimum should be 30% in a reproduction
      apiary. Such a level could be found in former Czechoslovakia in a honeybee
      breeding apiary (30-50%). In the author's opinion the invasion level of N. apis-
      20% of colonies--is too hard a programme for Polish conditions.

PMID- 9289931
TI  - The 3rd NO-Forum. Innsbruck, Austria, 21-23 March 1997. Abstracts.

PMID- 9289930
TI  - [Professor Zbigniew Stanislaw Pawlonski--jubilee celebration].

PMID- 9289928
TI  - [Delayed diagnosis of Trichinelliasis focused in the Poznan Province].
AB  - The study compares chronologically the weeks in which Trichinella spiralis
      infected meat was consumed. The first symptoms appeared and clinical diagnosis of
      trichinellosis was made in 37 patients. Several factors were responsible for the
      delay in final diagnosis of trichinellosis: widely distributed infected meat,
      contemporary common respiratory viral infections in population with fever and
      myalgia, diagnostic difficulties in the first index case.

PMID- 9289932
TI  - [Os odontoideum. A neurologic syndrome after orthopedic reduction of a C1-C2
      subluxation].
AB  - A case of os odontoideum associated with a C1-C2 subluxation is described. During
      the reduction procedure by external manipulation, bulging of the membrana
      tectoria resulted into medullary compression followed by a neurological syndrome.
      An occipito-C2 arthrodesis was performed later on when the neurological status
      recovered back to normal. The case reported underlines the possibility of
      neurological damage following closed reduction of a C1-C2 subluxation, while the
      surgical procedure should not be incriminated. The pathogenic mechanism may not
      be properly understood if closed reduction is followed by surgical treatment
      during the same session.

PMID- 9289933
TI  - [The philosophy of orthopedics].

PMID- 9289935
TI  - [Some thoughts on Bateman's equation].
AB  - The authors have investigated the characteristics of one of the basic equations
      of pharmacokinetics, Bateman's equation in the function of the differences
      between the absorption and elimination constants.

PMID- 9289934
TI  - [A unicompartment knee prosthesis: the effect of the positioning of the tibial
      plate on the functional results].
AB  - The authors analyse the results of 51 unicompartmental knee prostheses with 1 to
      12 years follow-up (mean follow-up: 5 years). The results were evaluated using
      the scoring system of the "Knee Group" of the SO.B.C.O.T. (Societe Belge de
      Chirurgie Orthopedique et de Traumatologie). This analysis demonstrates that the
      quality of the results depends on implant positioning. The authors suggest
      positioning the tibial implant parallel with the healthy plateau and slightly
      distal, i.e. to position the tibial implant perpendicular to the epiphyseal axis
      and not to the mechanical axis, as is systematically done with the usual tibial
      cutting guides. When this ideal positioning was respected, 77.5% of the patients
      had a score above 90 points (out of a possible maximum of 100 points) and 12.5%
      had a score between 75 and 89 points. When this condition was not respected, none
      of the knees obtained more than 75 points. The difference was statistically
      significant (p = 0.0001).

PMID- 9289936
TI  - [Validation of gas and liquid chromatographic methods in the bioanalytical
      laboratory].
AB  - The authors discuss the validation of bioanalytical methods used to generate data
      for bioavailability, bioequivalence and pharmacokinetics studies. The basis of
      this manuscript is a consensus on the requirements for bioanalytical validation,
      which has been reached by a panel of experts at the Washington Conference Report.
      In this paper it is attempted to suggest approaches to validation parameters both
      for the method and assay to be evaluated, namely specificity/selectivity,
      linearity, LOQ/LOD, accuracy, prescision, recovery and stability.

PMID- 9289937
TI  - [Pharmacokinetic study of nerisopam and its n-acetyl metabolite in rats].
AB  - Three doses were administered to the rats during the pharmacokinetic study of
      nerisopam and the plasma concentrations of nerisopam and its N-acetyl metabolite
      were determined parallelly by means of validated SPE-HPLC method developed by the
      authors. The pharmacokinetics of nerisopam could be described by a two
      compartment open model in rats, it was absorbed rapidly and could be measured in
      plasma for about 8 hours. The peak plasma concentration of the N-acetyl
      metabolite was reached rapidly a little bit later than that of the parent
      compound, similarly to the human plasma, and it could be measured for about 12
      hours. The pharmacokinetics of N-acetyl metabolite could be described by an one
      compartment open model. The fast appearance of the metabolite and the Cmax and
      AUC 0-infinity values higher than those of nerisopam refer to an intensive "first
      pass" metabolism. The AUC-dose curves indicate that supposingly the mechanism
      transforming the N-acetyl metabolites are not as fast as the acetylation.

PMID- 9289939
TI  - [Pharmaceutical technology of Tensiomin].
AB  - The physical chemical properties, stability and incompatibility of captopril (the
      active ingredient of Tensiomin tablets) have been discussed. Captopril has two
      polimorphic crystal modifications, the form I. of higher melting point is applied
      in the therapy. Captopril has a better stability in solutions below pH 4, the
      degradation is accelerated by metallic ions (Cu, Fe). In solid phase the
      degradation is accelerated by the humidity of the air. No incompatibility was
      found with the tabletting excipients but stearic acid and sodium-carboxymethyl
      starch. Under compaction at higher pressure captopril itself shows tendency for
      lamination. The dissolution rate of the Tensiomin tablets can meet the
      requirement of USP if direct tabletting method was used. In this case the
      breaking strength of the tablets has no influence on the dissolution rate. The
      main properties (weight uniformity, content uniformity, tensile strength,
      friability, disintegration time, dissolution time) of the Tensiomin tablets of
      12.5 mg, 25 mg, 50 mg and 100 mg of captopril meet the requirement of USP not
      only after manufacturing but after the accelerated stability test of three month
      as well.

PMID- 9289938
TI  - [Human pharmacokinetic study of nerisopam and its n-acetyl metabolite].
AB  - It was established during the human phase I study of nerisopam, a new anxiolytic
      drug, that nerisopam (EGIS-6775) shows two, while N-acetyl metabolite (EGIS-7649)
      shows one compartmental pharmacokinetic behaviour. Acetylation of nerisopam is
      polymorph, so that volunteers belonging into slow or fast acetylating group show
      significantly different plasma concentration. Observed pharmacokinetic
      differences are primarily manifested in the absorption phase, and not in the
      elimination one. Accordingly, slow acetylators have higher nerisopam levels,
      while fast acetylators possess higher metabolite levels. Elimination phase is
      practically parallel for both compounds. At the same time, significant
      differences are found in the AUC and Cmax values. Nerisopam is rapidly absorbed,
      but N-acetyl metabolite is appeared especially fast in the blood. Our
      consideration is, that nerisopam undergoes significant "first-pass" metabolism
      process, the extent of which is different between the two acetylator phenotypes.

PMID- 9289940
TI  - [Bioanalytic examination and pharmacokinetics of captopril. Bioequivalence
      studies of different captopril-containing Tensiomin preparations].
AB  - The authors of the present report reviewed the literature of various
      bioanalytical methods for the pharmacokinetics and metabolism of captopril and
      present their own results obtained in bioanalytical and pharmacokinetic studies.
      The authors performed a detailed comparative clinical, pharmacokinetic and
      bioequivalence study, in Hungary, with 3 different captopril tablets, 50 mg each,
      namely with Tensiomin (EGIS Pharmaceuticals Ltd.), as test preparation and
      Capoten (E.R. Squibb & Sons, Inc.) and Lopirin (Squibb Pharma GmbH) as reference
      preparations. Bioequivalence study of Tensiomin and Capoten preparations both
      containing 100 mg of captopril was carried out in the United States. Relative
      bioavailability and comparative pharmacokinetic parameters were determined in 24
      and 25 healthy volunteers, respectively, in single-dose, randomised studies of
      three-way (50 mg) or two-way (100 mg) cross-over design. The individual
      pharmacokinetic parameters determined for the test and reference preparations
      with different active principle content were tmax, Cmax, AUCOo-t, AUCo-infinity t
      beta 1/2, Cmax/AUCo-infinity. Statistical evaluation of the results of
      bioequivalence studies was made using confidence interval calculation and the
      Test/Reference ratio (50 and 100 mg), and by Schuirmann's, Hauck-Anderson's,
      Westlake's, Wilcoxon's methods (50 mg) and power test (100 mg). All the above
      tests indicated statistical equivalence between the test and reference
      preparations. The test and reference preparations of different strengths had
      identical relative bioavailability. Accordingly, the clinical and biological
      equivalence of 50 mg and 100 mg Tensiomin tablets with 50 mg and 100 mg Capoten
      tablets and 50 mg Lopirin tablet have been demonstrated in two independent
      comparative bioequivalence studies.

PMID- 9289941
TI  - [Report on the experience of clinical trials performed according to GCP].
AB  - As well known GCP is described more accurately by Good Clinical Research
      Practice, Good Clinical Trial Practice and Good Clinical Regulatory Practice. The
      Authority (National Institute of Pharmacy) from 1st January 1994 required that
      clinical trials phase I-II-III had to be performed in accordance with the GCP
      guideline (appeared in 1992 in edition of NIP). We tried to present in what
      follows a brief account of our experience considering the performance of clinical
      trials in accordance with Good Clinical Practice requirements.

PMID- 9289942
TI  - [Captopril treatment of hypertension].
AB  - After the brief description of the most important hypertensive pathophysiological
      processes (renin, angiotensins) which are closely related to angiotensin
      converting enzyme (ACE) inhibitors as well as to the mechanisms of action of
      captopril, author summarizes the essential clinical findings from the
      international and Hungarian literature. A short guideline for the administration
      of captopril to hypertensive patients is also given.

PMID- 9289943
TI  - [Use of captopril in therapeutic combinations].
AB  - The importance of captopril in the combined drug treatment of hypertension,
      congestive heart failure and ischemic heart disease is reviewed.

PMID- 9289944
TI  - [Captopril in the treatment of heart failure].
AB  - The author takes the characteristic hemodynamic features and neurohumoral factors
      associated with heart failure as the starting point for the discussion. He
      specifies fundamentals of the current strategies and goals of the management of
      heart failure. Treatment with vasodilatator and ACE inhibitors has paved novel
      way for treatment of heart failure, because it is not only able to alleviate the
      symptoms, but also to improve hemodynamic parameters and increase survival.
      Initiation of treatment at early stage (silent ventricular dysfunction) is able
      to prevent the development of manifest signs of heart failure. Captopril, a
      classical ACE inhibitor, is suitable for modern treatment of heart failure, as
      well for prevention of myocardial remodelling following acute myocardial
      infarction.

PMID- 9289945
TI  - Proceedings of the Vth Joint Meeting of the Hungarian, Polish and Italian
      Pharmacological Societies. Pecs, Hungary, 1996. Part I.

PMID- 9289946
TI  - Nutrition, Immunity, and Infection. Proceedings of a symposium. Madrid, Spain,
      October 24-25, 1994.

PMID- 9289947
TI  - Re:"Morton Levin (1904-1995): history in the making".

PMID- 9289948
TI  - Excerpts from United States Renal Data System 1997 Annual Data Report.

PMID- 9289949
TI  - [An analysis of the indications for episiotomy in current obstetrical practice].
AB  - The aim is to analyze the accepted indications for episiotomy in nowadays
      practice. The investigations is retrospective for the period from April to May
      1996. The material includes 459 term singleton pregnancy in vertex presentation
      and 46 cases of premature neonates with weight from 1300 to 1499 g. The results
      show high risk (77.1%) of episiotomy in nulliparous women. The multiparity, the
      length of second period and the high risk pregnancies have not effect on the use
      of episiotomy. The wight of the fetus is essential factor. The highest rate of
      episiotomy is at premature births (65.2%) followed by the group of neonates with
      weight over 4000 g (61.5%). The lowest rist of episiotomy is then the weight of
      newborn is between 2500 and 3800 g (21.8%). Almost hundred percent rate of
      episiotomy in operative vaginal and breech deliveries show that we accept the
      episiotomy as obligatory of these vaginal deliveries.

PMID- 9289950
TI  - [The use of cefotetan for the prevention of infectious postoperative
      complications in gynecology].
AB  - The study presents the results from the use of cefotetan for perioperative
      prophylaxis in 43 gynaecology patients compared with 29 controls without
      perioperative antibiotic prophylaxis with similar diseases and operations. Both
      groups show equal percentage of the cases with smooth postoperative period (70
      and 72% respectively). 13 of the patients on cefotetan prophylaxis received
      additional antibiotic treatment (9 because of temperature up to 37.5 degrees and
      4 because of temperature from 37.6 to 38.5 degrees). Mo major infections
      postoperative complications occurred among the patients on cefotetan prophylaxis.
      8 of the non-prophylacted patients needed antibiotic treatment postoperatively
      including 4 with temperature above 38.5 degrees. Two infections of the operative
      wounds also occurred in the same group. The conclusion is that cefotetan
      effectively prevents the major infection postoperative complications in
      gynaecology. The administration of additional antibiotic treatment is most often
      not warranted.

PMID- 9289951
TI  - [The appearance of ciprofloxacin resistance in the microbial strains isolated
      from gynecologic patients].
AB  - The sensitivity of 415 microbial strains isolated from clinically taken samples
      from gynecologically diseased women was determined. The urine strains showed
      sensitivity up to 93.3%, but 7 Gram/-/ strains isolated in the last 3 months of
      the study were resistant to Ciprofloxacin. The cervical secretion strains, those
      of CD aspirates, of IUP and wound secretions were found sensitive up to 81.2%.
      The 50 Enterococcus strains isolated in gynecological infections were found in
      28% resistant to Ciprofloxacin, with 7 of the 19 resistant strains were isolated
      in the last 3 months of the study. The appearance of resistant strains in some
      microbial species, pointed out in the literature as markedly sensitivity to
      Ciprofloxacin, as well as the data of a fast developed resistance Ciprofloxacin
      in the course of treatment, allowed us to recommend their application in the
      infections caused by microorganisms resistant to the habitual antibiotics.

PMID- 9289952
TI  - [Surgical pelvioscopy in gynecologic surgery].
AB  - The author tells his experience from the operative pelvioscopy performed on 350
      women. Using different surgery techniques he coagulates endometrial sites, he
      performs cystectomy, salpingostomy, myomectomy and ovarian biopsy. The most often
      diagnosis in these 350 cases is external endometriosis (43.14%), followed by an
      adhesiolysis of the Fallopian tubes end the ovaries (23.43%) and salpingoneostomy
      (10.57%). The percentage of pregnancy after an operative pelvioscopy performance
      is 27.89%. The author thinks a wide spectrum of interventions can be performed on
      the female internal genital organs with no need of more serious and damaging
      operations.

PMID- 9289953
TI  - [Changes in the amniotic fluid volume in fetal structural anomalies].

PMID- 9289954
TI  - [The ultrasonic diagnosis of endometrial pathological.processes in the
      postmenopause].
AB  - The diagnostic value of endovaginal ultrasound in some perimenopausal endometrial
      disorders has been evaluated. A search of the literature included in the Medline
      database system has been performed and more than 20 original papers were
      reviewed. Endovaginal ultrasound could play important diagnostic role in
      postmenopausal bleeding, but also in diagnosis, treatment, follow-up and
      screening of endometrial cancer.

PMID- 9289955
TI  - [The etiology and pathogenesis of the premenstrual syndrome].

PMID- 9289956
TI  - [Diagnostic difficulties in a degeneratively altered myoma].

PMID- 9289957
TI  - [A case of hemorrhage from a vaginal hematoma complicated by retroperitoneal and
      gluteal hematomas during labor ending with a cesarean section].

PMID- 9289958
TI  - [Mesodermal mixed tumors of the endometrium with a report of 7 cases].
AB  - Frequency and characteristics of mixed mesodermal tumors (MMT) and some
      terminology disparities in the comparatively scarce literature are discussed. The
      low frequency of MMT described and difficulties in diagnosing have been pointed
      out. A final diagnosis can be made on operative material only, since curettage
      contains one (more often the epithelial) of the components of biphase tumorous.
      The authors emphasize on guided attention to MMT, as well as the necessity of
      serial sections. The most important factor is depth of invasion.

PMID- 9289959
TI  - [The results of the limited use of episiotomy in managing the second stage of
      labor].
AB  - The purpose is to asses the effect of restrictive use of mediolateral episiotomy
      on the spontaneous laceration of the low birth canal. The material includes 613
      labors some of which gave birth with indication for episiotomy and control group
      of 441 retrospective cases with routine management of the second period of labor.
      The restrictive use of episiotomy decreases the rate from 45.6% in the routine
      practice to 32.8%. The reduced rate of episiotomy has as a consequent increase
      rate of second degree perineal laceration adn insignificant increase of vaginal
      lacerations. The management of restrictive and liberal use of mediolateral
      episiotomy has not effect on third and four degree perineal laceration, on the
      accessory tears of the vagina and on the rate of perineotomy. If from all labors
      are subtracted operative deliveries, surgical intervention for repairing the
      laceration of the birth canal and pathology of the placental period the rate of
      labors without any intervention is only 13.3%. Our results suggest that labor
      nowadays is operative activity.

PMID- 9289960
TI  - [The treatment of acute mycotic colpitis with ciclopiroxolamine in patients using
      oral contraceptives].
AB  - The author reveal the results of treatment with ciclopiroxolamine of women
      suffering from mycotic colpitis and using OC's. The research covers 26 women
      users of monophasic OC's with mycotic colpitis during the last 2-3 weeks before
      the research. The cause for the colpitis in 92% of cases is Candida albicans. The
      treatment was successful in 84.6% of the cases after the first 6-day-course with
      Batrafen creme. With 7.7% the treatment course with Batrafen creme was repeated,
      and with another 7.7% was included oral antimycotic (itraconazol). After
      treatment was performed microbiological check-up that confirmed the positive
      result of treatment. The authors' conclusion is that Batrafen creme is an
      effective device suitable for application on patients, CO's users.

PMID- 9289961
TI  - [A clinical study of the efficacy of and tolerance for the combined transdermal
      preparation Estracomb TTS (CIBA)].
AB  - Result from the first study, carried out in our country an the therapeutic
      effects of Estracomb TTS in women with peri- and postmenopausal symptoms are
      reported. Seven women with postcastration syndrome and eight women with an intact
      uterus and no vaginal bleeding for a least 6 months were treated. In all women
      enrolled in the study the application of the preparation Estracomb TTS led to a
      significant improvement of peri- and postmenopausal symptoms without serious side
      effects.

PMID- 9289962
TI  - [The use of the preparation Cilest in the practice of the Bulgarian Association
      for Family Planning].
AB  - Data are presented from a questionnaire study on the sexual activity of Bulgarian
      teenagers as well information on the contraceptive methods chosen by them. The
      authors inform in short about the activities of the Bulgarian Association for
      Family Planning (BAFP). Analyses are made of the data obtained from BAFP card
      index for the last two years. Information is given on the number of observed
      cycles, types of applied contraceptive method, aims of their application
      (contraception, treatment of acne, menstrual disturbances etc.). The attention
      was concentrated on the third generation contraceptive pills Cilest, on the age
      of patients, as well as on the adverse effects--change in blood pressure, body
      weight changes, intermenstrual bleeding, hairiness, breast problems, paraclinical
      changes, etc. Underlined is the number of teenagers who seen the BAFP help on
      problems of contemporary contraception. The observed cycles show a very small
      percentage of adverse effects with hormonal contraception, mainly during the
      first 2 of 3 cycles, with predominance of intermenstrual bleeding. No body-weight
      changes or increased hairiness were observed.

PMID- 9289964
TI  - [A single-stage double-layer suture for restoration of the uterine wall in
      cesarean section--our experience].
AB  - The author report, that in the Clinic of Obstetric & Gynaecology--St. Zagora,
      since 15 years, the uterine wall was reconstructed in two stories during
      caesarean section with continued catgut stitches. From 1990 they set the task to
      study prospectively the results of using the new surgical technics--one-stored,
      two-layered suture for reconstruction of the uterine wall during caesarean
      section. The received results of this method at 71 patients for 4 years & 5
      months are very good and they confirm the effectiveness of one-stored, two
      layered suture. The task is to enlarge the limits of using this technics from the
      others assistants in the clinic.

PMID- 9289963
TI  - [The use of Geniia vaginal suppositories in patients employing hormonal
      contraceptives].

PMID- 9289965
TI  - [A histogenetic classification of ovarian tumors].

PMID- 9289966
TI  - [Protracted labor ending with a cesarean section--a high-risk factor for
      puerperal infection].
AB  - The author undertakes a study to investigate the protracted delivery with
      different duration of prematurely ruptured membranes, to investigate and to
      compare the morbidity and structure of patients. To investigate the lochia
      secretions and to compare the microflora of the patients with ruptured membranes
      at different times with a view to their influence by antibiotic prophylaxis. At
      the end author makes appropriate conclusions.

PMID- 9289967
TI  - [The characteristics of labor in multifetal pregnancy based on our data].
AB  - The pregnancy and delivery in multifetal pregnancy most often are accompanied by
      complications and by a high degree of risk both for the mother and the foetus.
      The successful and of the delivery depends on the condition of the mother, the
      good obstetric status, the gestation age of the foetuses and their presentation.
      The authors have followed the characteristic of the delivery in multifetal
      pregnancy over 10-years material in 137 cases of pregnancy. After strict
      indications, in 26 cases the delivery has been completed though caesarean
      section. In 111 cases the delivery has been vaginal. A characteristic of the
      delivery has been made and it has been expressed in diagrams. The authors have
      been successful in the vaginal deliveries in multifetal pregnancy. They emphasize
      the active observation of the patient, especially in the first stage, and the
      monitoring of the foetus.

PMID- 9289968
TI  - [Fetal diaphragmatic hernia. Concomitant anomalies].
AB  - According to different investigations congenital diaphragmatic hernia (CDH) is
      associated with other anomalies in 29% to 53%. The aim of our study was to
      present our experience with the prenatal diagnosis of CDH and to analyse the
      associated anomalies. For a ten-year period there were 18 fetuses born after 24
      gestational week with CDH. The associated anomalies were found in 66.7%, most
      common they involved the nervous system, the heart and the kidneys. Our results
      confirm that there is a concentration of the most severe and with the worst
      prognosis cases of CDH in the bid neonatal centers.

PMID- 9289969
TI  - [Antibiotic prophylaxis in cesarean section with cefoxitin (Mefoxin)].
AB  - The ain of this presentation is to show the advantages and disadvantages of a
      single prophylactic dose of Mefoxin, in comparison to the classical antibiotic
      prophylaxis with penicillin and gentamicin. The authors conclude that: single
      dose prophylaxis with Mefoxin significantly reduces the rate of infection
      morbidity after caesarean section; a single application of 2 g Mefoxin after
      clamping of the umbilicus is enough for prophylaxis of infectious complications
      after caesarean section.

PMID- 9289970
TI  - [New advances in the treatment of climacteric disorders: quality of life in the
      menopausal and the elderly woman].

PMID- 9289971
TI  - [Surgery of the areola and the mammary ducts].

PMID- 9289972
TI  - [The physician before requested death].

PMID- 9289973
TI  - [New arguments with respect to the physiopathology of the polycystic ovary
      syndrome].

PMID- 9289974
TI  - [The Wertheim-Meigs operation].

PMID- 9289975
TI  - [Mechanism of propagation of tumors: metastasis, forms and main ways].

PMID- 9289976
TI  - [New possibilities in cataract surgery].

PMID- 9289977
TI  - [Antibiotics in emergency medicine].

PMID- 9289979
TI  - [Use of ofloxacin in the treatment of suppurative-inflammatory complications in
      surgery].
AB  - Analysis of ofloxacin use in clinical surgery over the latest decade showed that
      despite its wide clinical application for the prevention and therapy of
      postoperative complications, this drug remains highly active for the majority of
      micro-organisms. Hence, a wide spectrum, high bactericidal activity of the drug,
      optimal pharmacokinetics, and a high bio-availability (95-100%) still recommend
      ofloxacin, a highly effective agent for the treatment of infectious complications
      of surgery.

PMID- 9289978
TI  - [General and local antibiotic treatment with ceftriaxone of suppurative-septic
      diseases and complications].
AB  - A third-generation cephalosporin, Ceftriaxone, was used in intensive care of
      patients subjected to elective and urgent surgery in the Regional Clinical
      Hospital, St. Petersburg. A total of 105 patients were divided in 4 groups: 1) a
      course of ceftriaxone in combination with aminoglycosides started before the
      intervention; 2) the same, with the disease course complicated by peritonitis; 3)
      patients with neurosurgical diseases and brain injuries complicated by secondary
      meningoencephalitis; and 4) abdominal surgical patients in whom the severity of
      illness was determined by the abdominal process of different localization. The
      treatment included general and local use of ceftriaxone under ultrasonic control.
      The results indicate that ceftriaxone is a broad-spectrum drug effective in the
      treatment of nosocomial infections and neuroinfections; it can be applied locally
      and is economic.

PMID- 9289980
TI  - [Filtration of media for infusion-transfusion therapy as a measure of prevention
      of systemic inflammatory reaction in surgery using artificial blood circulation].
AB  - Sixty-five coronary patients were subjected to aortocoronary bypass surgery.
      Three groups were distinguished: 1) controls-no filters; 2) patients in whom
      hemotransfusion (40 mu) and infusion filters were used during and on day 1 after
      surgery; and 3) in whom leukocyte filters for filtering residual perfusate from
      artificial circulation device were used in addition to the filters used in group
      2. In the controls plasma level of leukocytic alpha-glycoprotein after artificial
      circulation increased 22 to 36 times, whereas in groups 2 and 3 it did not
      increase at all. After surgery the severity of leukocytosis, hyperthermia, and
      hyperenzymia assessed from the level of SGOT was reliably lower in patients in
      whom the filters were used. The time course of the oxygenation index (PaO2/FiO2)
      indicated an improvement of gas exchange due to filtration of infusion
      transfusion media. The minimal values of PaO2/FiO2) and plasma content of C
      reactive protein were observed in group 3. The mechanisms of systemic
      inflammatory reaction and organ dysfunction and some aspects of the protective
      effect of filters are discussed.

PMID- 9289982
TI  - [Severe sepsis and multiple organ failure in surgical patients in intensive care
      unit of oncological profile].
AB  - Forty-seven cases with grave sepsis and multiple organ failure in patients
      operated on for malignant tumors of different localizations and treated in
      intensive care wards of Cancer Research Center in 1996 are analyzed. In 35
      patients sepsis developed due to pyoseptic complications of surgery and led to
      multiple organ failure, in 12 sepsis complicated multiple organ failure of other
      origin. Four or five organ systems were involved in 2/3 of patients with
      "primary" sepsis and in almost all patients with "secondary" sepsis. Sepsis and
      multiple organ failure in surgical cancer patients are believed to differ much
      from those in general surgical patients, which is explained by the scope of
      intervention, a tendency to decrease the number of indications for surgery, and
      by profound impairment of immunity and metabolism.

PMID- 9289981
TI  - [Diagnosis of the stage of adult respiratory distress syndrome in patients with
      peritonitis].
AB  - The respiratory function of the lungs was examined in 68 patients with diffuse
      peritonitis of different origin in the early postoperative period by laboratory,
      instrumental, and statistical methods and assessed by expert evaluation. The
      training sampling included 275 cases expertly classified as follows: health,
      stage I respiratory distress syndrome of adults (RDSAI), RDSAII, RDSAIII, and
      RDSAIV. Discriminant analysis was carried out fir the first four classes of
      patients. The best results were obtained when the following 6 variables were
      used: respiration rate, assessment of the irregularity of ventilation perfusion
      ratio (delta p/delta t), end-expiration maximal tension of carbon dioxide
      (FetCO2), resistance of the body site between the measuring electrodes in the
      course of tetrapolar chest rheography (Z), and arterial capillary blood pCO2 and
      pO2. The resultant discriminant functions permit the diagnosis of RDSA and help
      determine the stage of the syndrome development with a probability of at least
      90%, which may be used clinically to validate the conclusion of a physician
      concerning correction of the treatment policy in this patient population.

PMID- 9289983
TI  - [Enterosorption in intestinal failure syndrome].

PMID- 9289984
TI  - [New possibilities in prevention and correction of postoperative suppurative
      septic complications and multiple organ failure in oncological surgery].
AB  - The functional status of the oxidative-antioxidative system was studied in 72
      patients after vast cancer operations. Traditional surgical treatment and its
      combination with intraoperative irradiation were shown to lead to tense
      antioxidative defense and to suppressed T-cell immunity and to call for
      antioxidative and immunomodulating therapy. High intraoperative blood loss
      complicated by hemorrhagic shock injured the oxidative-antioxidative system
      greatly. The magnitude of this damage correlated with the rate of prehypoxia.
      Addition of the potent antioxidant Ceruloplasmin to the drug regimen normalized a
      recovery period, helped to correct posthypoxic multiorgan insufficiency, to
      recover oxidative-antioxidative balance, and to decrease the incidence of
      pyoinflammatory complications. Patients with endogenous intoxication showed
      activated lipid peroxidation, decreased functional activity of antioxidative
      defense components and of T-cell immunity in homeostasis. The use of
      Ceruloplasmin and Laprot had pronounced antiinflammatory and detoxifying effects
      on the patient's body and activated its antioxidative defense.

PMID- 9289985
TI  - [Nosocomial infections in intensive care].
AB  - Nosocomial infection remains a pressing problem of surgery and intensive care.
      The authors analyze the sources of infection, the factors predisposing to it, and
      the pathogenetic aspects. The strategy of nosocomial infection control is
      determined by the clinical and nosological structure and severity of patients'
      status. Microbiological and pharmacological studies helped the authors develop
      the protocols of the initial and alternative antibiotic therapy of various
      nosocomial complications of wound infection, abdominal sepsis, nosocomial
      pneumonia, and infectious toxic shock. Experience gained by the authors permitted
      them to recommend preventive measures decreasing the risk of exo- and endogenous
      infection and improving the mechanisms of patients' immunity.

PMID- 9289986
TI  - [Extrarenal purification of blood in patients with multiple organ failure:
      results and prognostic criteria].
AB  - Acetate hemodialysis (HD) with an artificial kidney an continuous hemofiltration
      were used in the treatment of 49 patients with the multiple organ failure
      syndrome (MOFS) developing as a complication of aortocoronary and mammary
      coronary shunting and heart valve replacement. MOFS involved failure of the
      function of 3.5 +/- 0.2 vital organs on average. Acute circulatory disorders were
      observed in 100% of patients, acute renal failure in 75.5%, and perioperative
      myocardial infarction in 34.7%. In 93.9% of patients HD and HF were combined with
      forced ventilation of the lungs, in 97.9% with catecholamine infusion, in 26.5%
      with assisted circulation, and in 57.1% with the Swan-Ganz monitoring of the
      central hemodynamics and of oxygen transporting function of circulation. Multiple
      modality intensive care resulted in survival of 21 (42.8%) patients. The survival
      of patients with MOFS depended on the number of involved organs, method of
      extracorporeal detoxication, and monitoring of central hemodynamics and oxygen
      transporting function of the blood. Acute renal failure, respiratory distress
      syndrome, and shock deteriorated the prognosis for patients with MOFS.

PMID- 9289988
TI  - [Experience in the treatment of severe forms of sepsis by extracorporeal therapy
      and hyperbaric oxygenation].
AB  - The results of multiple modality treatment of 81 patients with sepsis complicated
      by multiple organ failure are assessed. In 40 patients the traditional therapy of
      sepsis was supplemented with extracorporeal methods (hemoperfusion,
      autotransfusion of UV-exposed blood, and perfusion of xenospleen slices) and
      hyperbaric oxygenation (HBO) sessions. In the patients treated traditionally the
      mortality was 94%, whereas addition of extracorporeal treatment and HBO decreased
      this value to 40%. Hence, extracorporeal treatment and HBO are recommended for
      the treatment of sepsis.

PMID- 9289987
TI  - [Low-flow membrane oxygenation of blood in patients with diffuse purulent
      peritonitis].
AB  - Small-flow membranous oxygenation of the blood was used in 45 patients with
      peritonitis in the multiple organ failure phase. In ten cases blood oxygenation
      was combined with hemofiltration. MOCT 19-03 (Kvant Research and Production Unit)
      and Gambro FH hemofilters (Sweden) were employed. Combination of small-flow
      membranous oxygenation of the blood combined with hemofiltration appreciably
      improved the oxygen-transporting function of the blood in adult patients with the
      respiratory distress syndrome, which was due to mutual potentiation of the two
      methods' effects. Small-flow membraneous oxygenation alone improved cellular
      immunity and decreased the laboratory manifestations of endogenous intoxication
      due to biotransformation of toxic products.

PMID- 9289990
TI  - [Lymph dilution as a method of treatment in endotoxicosis].
AB  - Lymph dilution was used in 26 females with inflammation of the uterine appendages
      and 22 patients with appendicular infiltrate. 500 ml of sodium chloride solution
      with gentamycin (1.4 mg/kg) were dripped in the subcutaneous fat of the femur
      anterior surface. Pneumocompression was performed on the unit APKU-5. The
      response was identical to the direct endolymphatic antibiotic therapy.

PMID- 9289991
TI  - [Plasma contents of cytokines (TNF-alpha, IL-1 beta, IL-6) and their clearance
      during continuous hemofiltration in patients with sepsis and multiple organ
      failure].
AB  - The total-systems inflammatory response was assessed in patients with sepsis and
      multiple organ failure by measuring plasma cytokines TNF-alpha, IL-1 beta, and IL
      6 and their clearance and total elimination in the course of permanent
      hemofiltration (PHF). Sepsis and multiple organ failure were found to involve a
      stable circulation of numerous cytokines, their levels reaching the peaks in some
      cases. No correlation between the content of individual cytokines in the plasma
      were detected. Appreciable amounts of TNF-alpha and IL-1 beta were eliminated
      during PHF, their clearance being approximately 15 ml/min, whereas elimination of
      IL-6 was negligible. Hence, PHF affects the mediator component in the
      pathogenesis of sepsis and the multiple organ failure syndrome.

PMID- 9289989
TI  - [Indirect electrochemical oxidation of blood in multimodal intensive therapy of
      pneumonia in critical patients].
AB  - Seventy-five patients with severe pneumonia were treated with sodium hypochlorite
      solution (intravenous drip in concentration 600 mg/liter). Beneficial effect of
      the treatment manifested with lowering of body temperature, diminution of
      tachycardia, leukocytosis, leukocytic intoxication index. The patients recovered
      5-7 days earlier, the mortality reduced by 11%. Better clinical parameters were
      due rather to stimulation of anti-infection defence than to direct detoxication
      action of sodium hypochlorite on the causative agent and toxic products. The
      solution is recommended for treatment of critical pneumonia as an effective
      modality with immunostimulating, antiinfectious and detoxication abilities.

PMID- 9289992
TI  - [Endogenous intoxication and its treatment with sodium hypochlorite in
      neurosurgical patients].
AB  - Blood plasma levels of medium-mass molecules (MMM), antioxidant activity (AOA),
      and malonic dialdehyde (MDA) were measured in 51 neurosurgical patients before
      and directly and 24 h after intravenous drip infusion of sodium hypochlorite
      (SHC) solution. Preliminary in vitro studies showed the most expressed drop of
      initially high MDA and MMM levels to be associated with an increase of AOA. It
      was observed at SHC concentration of 0.05 mg/ml, corresponding to infusion of SHC
      in a concentration of 600 mg/liter in 0.1 of the total circulating blood volume.
      Even a single dose of SHC alleviated endogenous intoxication and decreased the
      concentration of MMM and lipid peroxidation products. The proper AOA of the blood
      did not drop in this case, and in patients with initially low AOA it appreciably
      increased. Infusion of SHC normalized the values of Kp, which reflected its high
      detoxifying activity in endogenous poisoning caused mainly by inflammatory
      changes.

PMID- 9289993
TI  - [Relationship of disorders of transcapillary fluid exchange in the lungs and
      respiratory mechanics in postoperative pulmonary complications].
AB  - The central hemodynamics, external respiration function, and transcapillary
      liquid exchange in the lungs were assessed in 23 patients operated on the lungs
      and in 18 subjected to open heart surgery. The content of extravascular liquid in
      the lungs was increased during the first hours postoperation in the patients with
      a complicated course of the postoperative period, in contrast to those with an
      uneventful course thereof. Disorders of transcapillary liquid exchange did not
      depend on the status of the central hemodynamics and probably reflected the
      increased permeability of the alveolocapillary membrane.

PMID- 9289994
TI  - [Hemo-hydrodynamic monitoring in intensive care of patients with severe course of
      peritonitis].
AB  - The central hemodynamics and aqueous spaces of the body were examined in patients
      with peritonitis running a grave clinical course. The authors developed rational
      methods to correct the hemodynamics and water balance at different stages of
      treating peritonitis and infectious toxic shock. Continuous hemohydrodynamic
      monitoring is recommended to be used during intensive care of patients with
      infectious toxic shock.

PMID- 9289995
TI  - [Physical features of high-frequency artificial ventilation of lungs].
AB  - The authors analyze main features of high-frequency forced ventilation of the
      lungs (HF FVL). Estimations indicate that the end-respiration pulmonary positive
      pressure inevitably develops during HF FVL; its value is 30 cm H2O and it starts
      no later than 10 sec after the beginning of HF FVL. Experiments showed that the
      maximal and minimal pressure of the respiratory cycle measured at the site
      accessible for measurements outside the device (at the exit) differ appreciably
      from pulmonary pressure which is clinically impossible to measure but is much
      more valuable. For assessing this value the mean respiratory cycle pressure is to
      be measured whose values outside the device and inside the lungs are similar and
      virtually do not change if the frequency of HF FVL changes. The volume of dead
      space and internal elasticity of common FVL devices influence appreciably the
      created minute ventilation, particularly its alveolar component, and the
      probability of using such devices for HF FVL is doubtful. Requirements to the
      injector design for the most frequently used injection HF FVL are contradictory.
      A reasonable compromise on providing the needed consumption of inhaled gas and
      oxygen concentration in it within a sufficiently wide range of pressure may be
      attained by supplementing the device with a kit of special injectors. Estimations
      of gas movement in the airways do not validate the hypothesis on the turbulence
      in the transitory and respiratory zones of the tracheobronchial tree as a factor
      explaining the efficacy of HF FVL with low respiratory volumes.

PMID- 9289996
TI  - [Clinical value of blood lactate measurements].

PMID- 9289997
TI  - [Role of antibiotics in the prophylaxis of surgical infections. A comparative
      analysis of short-acting and long-acting antibiotics].

PMID- 9289998
TI  - [Exchange plasmapheresis in surgical diseases of abdominal cavity organs].

PMID- 9289999
TI  - [Pharmacological correction of low cardiac output syndrome in hemofiltration].
AB  - Low cardiac output was corrected by catecholamines in the course of
      hemofiltration (HF) administered to 37 patients with multiple organ failure after
      surgery. Catecholamines (adrenaline hydrochloride, noradrenaline hydrotartrate,
      dopamine hydrochloride, and dobutamine hydrochloride) were used as monotherapy or
      in various combinations (two, three, or four drugs). Ninety percent of patients
      with low cardiac output subjected to HF were administered combined catecholamine
      therapy. Catecholamines provided the hemodynamic stability of HF in patients with
      low cardiac output. The frequency of noradrenaline administrations and its mean
      doses were reliably decreased in the course of HF, whereas the mean doses of
      adrenaline, dopamine, and dobutamine remained virtually the same.

PMID- 9290000
TI  - [Immunotherapy of sepsis: myth or reality?].

PMID- 9290003
TI  - [The First Conference of University Surgeons].

PMID- 9290001
TI  - [Hypoxia and its pharmacological correction: a key problem of anesthesiology and
      intensive care].

PMID- 9290002
TI  - [Low-intensity laser irradiation in the treatment and prevention of complications
      of catheterization of the subclavian vein].

PMID- 9290004
TI  - [The "mixed" hospital department for clinical and rehabilitation purposes].

PMID- 9290005
TI  - [Benign lesions of the breast].
AB  - Benign lesions represent the most frequent lesions of the breast. Such lesions
      often onset with nodules or palpable masses simulating a breast cancer. In
      uncertain cases, an excisional biopsy may be at the same time a diagnostic and a
      therapeutic solution. A high percentage (40%) of the diagnosed lesions belongs to
      fibrocystic disease. A remaining 50% can be shared among tumor-like lesions,
      inflammatory lesions or benign tumors like fibroadenomas. Only in the 10% of
      palpable breast masses, biopsy reveals a breast cancer. The role of the
      pathologist is strictly related to the surgeon's one. Clinically benign lesions
      may be excised throughout a biopsy performed under local anesthesia. Clinically
      uncertain lesion must be evaluated by a fine needle aspiration biopsy (FNAB),
      nevertheless in some cases the doubt may persist. In such cases an excisional
      biopsy performed while the patient is under general anesthesia may finally solve
      the question. In case of breast malignancies the intervention can be enlarged as
      described for cancer.

PMID- 9290006
TI  - [Clinical manifestations in benign breast diseases. The surgeon's role in the
      evaluation of signs and diagnostic work-up].
AB  - From January 1988 through December 1995, 1022 patients having a breast disease
      have been operated on in our center. Of them 342 had a breast malignancies
      whereas 680 beared a benign breast disease. Benign breast pathology presents to
      the physician two main problems, they are: i) the need to rule out a breast
      cancer, which often may be simulated by special clinical presentation ii) the
      need to determine if eventually such a benign lesion can degenerate into a
      malignancy. We conclude according to our experience and following several authors
      that although a very careful diagnostic evaluation must be performed for every
      breast lesion, only few benign lesions arising with particular patterns can
      change into a breast cancer.

PMID- 9290007
TI  - [The role of imaging techniques in benign breast lesions].
AB  - Imaging techniques in breast pathology represent a basic complement to clinical
      and histopathological examinations. The combined use of these diagnostic
      procedures allows in the 90-95% of all cases a preoperative diagnosis of the
      lesion. Our fifteen years experience, made of thousands of examinations,
      supported from the data from current literature lead us to stress on one side the
      efficacy of mammography, that may be considered one of the three basic step in
      the differentiation of benign from malignant lesions and on the other hand the
      importance of ultrasonography (US). Especially US seems to have a high
      sensitivity in examining the juvenile breast, which is more often source of
      benign pathology. Mammography, when supported by a stereotactic equipment, which
      enables the surgeon to perform a wire guided biopsy, may further reduce the need
      for intraoperative histopathological examinations, which often have to be done
      under general anaesthesia. Old or controversial imaging devices like thermography
      or diafanoscopy appear to have no more role in the preoperative diagnosis of
      breast masses. Newer techniques like nuclear magnetic resonance or breast
      scintigraphy with 99-Tc have not gained an exact role yet.

PMID- 9290008
TI  - [Cytopathology in the diagnosis of benign breast lesions].
AB  - In this review dealing with cytologic features of non-malignant diseases of the
      breast, authors try to correlate cytopathologic findings with clinical condition.
      Five different clinical presentations are recognized: cystic nodule, solid
      nodule, not palpable lesions, spontaneous secretion, mastitis. An overview of
      literature data is provided by authors who emphasize either reliability or
      specificity of cytopathological methodologies. Furthermore, they conclude that
      along with clinico-radiologic diagnostic procedures, cytology represents a
      mainstay for prognostic assessment and presurgical evaluation of breast lesions.

PMID- 9290009
TI  - [Benign breast diseases: the surgeon's role in its treatment].
AB  - INTRODUCTION: Surgery plays a key role in the diagnosis and treatment of breast
      diseases. Diagnostic answers and therapeutic solutions are offered thanks to
      surgery for both benign and malignant situations. PATIENTS AND METHODS: From
      January 1975 to August 1995 in our centre 1933 breast biopsy for benign breast
      diseases have been performed. In 98% of all cases the intervention has been
      performed under local anesthesia throughout the infiltration of 5 to 40 cc of
      Lidocaine or Mepivacaine. RESULTS: Mortality in our series was 0. Morbidity
      affected the 0.75% of all operated cases with hematomas or wound infections.
      DISCUSSION: Surgery becomes the solution in the diagnosis of breast diseases
      whenever previous diagnostic steps (Clinical examination+mammography+FNAB) or
      (Clinical examination+Ultrasonography+FNAB) or (Clinical examination+FNAB) fail
      to reveal a preoperative diagnosis. Of course surgery represents also the logical
      treatment of previously diagnosed lesions. The surgical excision of benign
      lesions must be meticulous due to the high recurrency rate that some of these
      lesions have (some histotype of fibrocystic disease or phyllodes tumors).
      Moreover surgery due to the benign nature of the lesions and to the fact that
      most part of the patients is represented by young women should always be as
      conservative and aesthetic as possible, by following anatomic lines and calibre
      sutures.

PMID- 9290010
TI  - [Our experience in the surgical treatment of early breast cancer. Results of a
      prospective study of 204 cases].
AB  - The authors report the results of a prospective study on 204 patients (1980-1993)
      affected by early infiltrating breast cancer (size pounds 2 cm) as a part of a
      surgical series of 608 cases. 53 cases who underwent QUART (25.9%) and 151 cases
      (74.1%) who underwent mastectomy modified according to Patey have been collected.
      10 years actuarial survival has been respectively 79% after extensive surgery and
      78% after conservative treatment. Local recurrences have been observed in 9 cases
      after meticulous follow-up (median 74.8 months, range 12-178): 3 (5.66%) patients
      after QUART and 6 (3.97%) after mastectomy; furthermore 1 patients after a
      conservative treatment (1.88%) has developed a second tumor at the same side
      probably dependent on the presence in the primary tumor of an extensive
      intraductal component. No correlations between histological features, grading,
      positive nodes, receptor status and local recurrences have been found. Only the
      age of patients looks significantly correlated with frequency of recurrences:
      44.45% of local recurrences have been observed in patients less than 45 years
      old. Local recurrences after QUART have obliged, in all cases, to a radical
      mastectomy. Furthermore, frequency of distant metastases has been considered:
      after QUART percentage is lower (9.43%) than after radical mastectomy (13.9%).
      This consideration looks correlated with the longer follow-up of the later group.
      A multidisciplinary approach is advised but the most important role is played by
      surgery. In conclusion it is outlined that conservative surgery is addressed to
      selection and consenting patients.

PMID- 9290011
TI  - [Primary lymphoma of the breast. Three cases of non-Hodgkin lymphoma].
AB  - Primary and sole breast lymphoma is a very rare disease. With the review of our
      series of 616 cases operated on for breast cancer, only 3 cases (0.48%) of
      primary breast non-Hodgkin lymphoma (LNH) have been observed. The authors outline
      the problems concerning diagnosis and therapy of this rare disease: pathological
      and immunohistochemical aspects are discussed. They stress the importance of
      staging in order to plan a correct multidisciplinary approach.

PMID- 9290012
TI  - [New directions in the surgical treatment of gastroesophageal reflux. Review of
      the literature].
AB  - The pathophysiology of gastroesophageal reflux disease (GERD) is often
      multifactorial, as abnormal function of the lower esophageal sphincter (LES) may
      be associated to abnormalities of the esophageal peristalsis, the esophageal
      clearance, and the gastric reservoir. The preoperative evaluation of patients
      with GERD must include esophageal function tests (esophageal manometry and
      ambulatory pH monitoring) and evaluation of the gastric emptying in addition to
      UGI series and endoscopy. The information provided by these tests is essential to
      identify the pathophysiology of the disease in the individual patient, and tailor
      the operative treatment accordingly. For patients with an incompetent LES but
      normal esophageal peristalsis, the Nissen fundoplication is the procedure of
      choice. When abnormal peristalsis and delayed clearance are identified by
      preoperative esophageal function tests, a partial fundoplication must be chosen
      in order to avoid postoperative dysphagia and gas bloat syndrome. Too many
      eponyms have been used to describe antireflux surgery (Nissen, Rossetti, Toupet,
      Lind, Hill, Guarner). It is time to go beyond these eponyms, and focus on the
      technical details which contribute to the stability of the wrap, as this is the
      main determinant of long term outcome.

PMID- 9290013
TI  - ["Killing" of pseudomonas aeruginosa isolated from patients with critical post
      operative complications. Effect of various antibiotics].
AB  - We undertook this study to estimate phagocytic killing by neutrophils (PMNs) of
      Pseudomonas aeruginosa pre-exposed to sub-inhibitory concentration of Amikacin
      and Imipenem. In particular, we have isolated bacteria from endotracheal
      aspirates of post-operative patients mechanically ventilated admitted to an ICU
      with respiratory failure. PMNs were obtained both from these patients (Group A,
      n. 6) as well as from subjects submitted to surgery with uncomplicated post
      operative period (Group B, n. 8). From specimens tested, 6 strains of Pseudomonas
      aeruginosa were isolated. Results showed that the rate of killing of bacteria
      treated with Amikacin was no different from that of untreated bacteria, whichever
      the source of PMNs, either from Group A or Group B patients. On the other hand,
      the microbicidal effect on P. aeruginosa exposed to Imipenem was significantly
      enhanced when PMNs were obtained from Group B patients. In the mixture bacteria,
      Imipenem and PMNs obtained from Group A the rate of killing was low, similar to
      the controls without antibiotics. Such a finding suggests a possible impairment
      of PMNs due to the critical disease and in some way responsible for the host
      adverse interaction between granulocytes, antibiotics and pathogens. The
      underlying mechanisms remain to be clarified and further studies are required to
      understand the possible clinical implications.

PMID- 9290015
TI  - [Cholecysto-colic fistula: laparoscopic treatment].
AB  - Cholecystocolic fistula is an unusual complication of biliary tract disease and
      it may defeat laparoscopic treatment. We recently was a patient who, while
      undergoing laparoscopic cholecystectomy, was found to have a fistula between the
      gallbladder and the transverse colon. The fistula was transected with a 3 cm
      endoscopic linear stapling device and uneventful laparoscopic cholecystectomy was
      performed. This report shows that, with increasing experience, no absolute
      contraindications exist to starting laparoscopic cholecystectomy by introducing
      the laparoscope.

PMID- 9290014
TI  - [The importance of pre-operative ultrasonography in assessing the technical
      difficulty and potential complications of laparoscopic cholecystectomy].
AB  - In this work thirty patients with symphtomatic not complicated gallbladder
      disease were studied by ultrasound (US) and by oral-cholecystography, to value
      the correlation between the results and the surgical judgement of laparoscopic
      cholecystectomy (LC) difficulty level (by Visual Analogue Scale). Wall thickening
      and diminished gallbladder function were significantly (P < 0.001) associated
      with increased technical difficulty of LC. Moreover the US evaluation of Veress's
      needle insertion seat is helpful. There was no significantly association between
      LC operative difficulty and volume and other US parameters (P > 0.05). Basing on
      results and on literature review, US and oral-cholecystography can be considered
      as predictors of LC operative difficulties and it can be used as a screening.

PMID- 9290016
TI  - [The use of laser through thoracoscopy in the treatment of spontaneous
      pneumothorax. Presentation of a clinical case].
AB  - The authors present the case of a patient with right plurirecidive pneumothorax.
      During the 12 months before the operation the patient suffered from 3 episodes of
      pneumothorax, treated with the insertion of an intrapleural drainage.
      Preoperative exams showed the presence of multiple emphysematous blebs with
      diameter ranging from 0.5 cm to 3 cm. The patient was treated with Nd:YAG laser
      photocoagulation of the blebs and mechanical abrasion of the parietal pleura
      through thoracoscopy. The laser photocoagulation of the blebs was performed using
      the contact technique and a 25 Watt power. After operation a TX of the thorax,
      using the high resolution technique, showed the presence of residual blebs
      involving the apex and the mediastinal surface of the inferior lobe of the right
      lung. After a 12 month follow-up no recidive pneumothorax occurred and the
      general conditions of the patient were good. The authors state that the laser
      treatment of spontaneous pneumothorax secondary to bullous emphysema is effective
      and safe and it is also successful in patients with multiple blebs. As it is
      often difficult to find and treat all the blebs, it may be useful to perform
      thoracography during thoracoscopy.

PMID- 9290017
TI  - ["Banding" of the venous side of an arteriovenous fistula for hemodialysis
      complicated with steal syndrome: a clinical case].
AB  - The duration of an arteriovenous fistula has a limit. In fact there are some
      complications that compromise a good working of them. We have dealed on of these
      complications, a steal syndrome of an omero-cephalic fistula by a simple
      operation of "banding" using a ring of Teflon around the arterialized vein
      getting a good clinical result with a good preservation of the blood flow trans
      fistula.

PMID- 9290019
TI  - [Chronic inflammation of mucous membranes: integration of immunity and
      regeneration].
AB  - Lymphoid tissue of mucous membranes is a morphological basis for local immunity.
      Lymphocytes of mucous membranes are bifunctional: reception of antigenic
      information and regulation of epithelial cells regeneration. The following
      structural manifestations of intercellular interactions are discussed: expression
      of HLA-DR antigens by the epithelium and endotheliocytes transforming them into
      "facultative" antigen-presenting cells; polyclonal plasmocyte proliferation; the
      exchange of their prevailing IgA phenotype for IgG; cytotoxic and cytogenetic
      effect of the interepithelial lymphocytes.

PMID- 9290018
TI  - [Plasma-cell granuloma of the sigmoid colon concomitant with adenocarcinoma of
      the cecum. Viewpoint for debate, literature review on pseudotumors, idiopathic
      colitis and cancer].
AB  - A case of colonic pseudotumor, causing intestinal occlusion, concomitant with a
      caecum neoplasia is reported. A male 69 years old was referred to our Institution
      for colic abdominal pain: colonoscopy aborted because of an insuperable sigma
      stenosis; diagnostic enema confirmed the sigmoid stenosis, originally advised as
      neoplastic. As operation, the sigmoid tumor appeared accompanied with enlarged
      draining lymph nodes and peritoneal sac was disseminated of miliary-like whity
      granules. Hystological examination showed a plasma-cell granuloma with nodular
      and peritoneal chronic inflammatory reaction. A pancolonoscopy, performed fourty
      days later, discovered an unsuspected adenocarcinoma neoplasia of the caecum,
      that was resected with a second operation. Regional nodes were not involved. The
      authors make a review of international literature about of plasma-cell granuloma,
      pseudotumor and inflammatory chronic bowel diseases in order to identify possible
      correlations between pseudotumor and neoplasms. The extremely low incidence of
      plasma-cell granulomas in the alimentary tract (17 case since 1970 to 1994) and
      the reported association with concomitant neoplasms (29%) suggest to consider
      extremely useful an accurate study of patients with intestinal pseudotumors in
      order to identify neoplasms of the gastrointestinal tract as well as of other
      organs.

PMID- 9290021
TI  - [Functional morphology of the adenohypophysis in gastric precancer and cancer].
AB  - 135 hypophyses of patients who had died of stomach precancer and cancer versus
      those of healthy controls were studied by histochemical methods allowing to
      distinguish various hormone producing cells. Participation of ACTH, TTH in the
      antitumor protection and that of FSH, LM, LTH and STH in the promotion and
      progression of stomach cancer is shown.

PMID- 9290020
TI  - [Sex hormone receptors in the gastric mucosa in gastric precancer and cancer].
AB  - Sex hormones receptors from 240 patients with stomach cancer and precancer were
      studied using an immunoperoxidase method. Reception of steroid hormones was shown
      to influence stomach cancer development while the "perversion" of this reaction
      may determine unfavourable prognosis.

PMID- 9290022
TI  - [A new international morphologic classification of gastritis (modification of the
      Sydney system)].
AB  - A new international classification of gastritis retained basic principles of the
      Sydney system-combination in the diagnosis of etiology, topography and
      morphological features. This makes the diagnosis close to the nosological one.
      The advantage of the classification is its visual-analogous scale of evaluation
      of the morphological changes degree. It will ensure higher reproducibility of the
      morphological results and will decrease the controversies between morphologists.
      Subdivision of chronic atrophic gastritis into the subtypes-autoimmune (etiology)
      and multifocal (morphology)-is lame. Likewise, so-called peculiar forms of
      gastritis are not covered. Nevertheless, this modified classification may be
      considered as acceptable for diagnostic and research goals.

PMID- 9290023
TI  - [Hypophysis compression syndrome in the sella turcica: mechanisms of development,
      pathology].
AB  - Intrasellar hypertension--a phenomenon of the hypophysis compression in the sella
      turcica-was described 13 years ago. It develops under stressor conditions and is
      probably one of the causes of frequent in critical situations (shock, collapse,
      coma, etc.) episodes of acute hypophyseo-adrenal failure. Intrasellar
      hypertension morphologically manifests by the volume unbalance between a suddenly
      increasing, 1.5-2 times, hypophysis (due to adenocyte hypertrophy, hyperemia,
      colloid retention) on the one hand, and its rigid capsule and sella turcica, on
      the other. Extrahypophyseal factors (high liquid and venous pressure) may take
      part in developing of this phenomenon due to hypophysis squeezing from outside.

PMID- 9290024
TI  - [Pathomorphology of the kidneys in hemolytic-uremic syndrome in children].
AB  - The kidneys were studied morphologically in 64 cases of hemolytic-uremic syndrome
      (HUS) in children aged from 17 days to 4 years. Three variants of the kidney
      alterations are distinguished depending on the duration of acute renal failure
      (ARF): early, late and delayed alterations. Early alterations were observed if
      ARF lasted for 1-10 days and were characterized by glomerular thrombotic
      microangiopathy with disturbance of the nephron proximal part function resultant
      from microcirculatory damage. Late kidney alterations (11-20 days of ARF)
      consisted of glomerular thrombi fibrinolysis, development of mesangial cell
      proliferation and mesangiolysis, proximal tubular epithelium regeneration and the
      appearance of nephrohydrosis resulting from the distal nephron part obstruction
      by hyalin cylinders. Delayed alterations (21-62 days of ARF) manifested with
      predominant atrophic and sclerotic processes. The first variant corresponded to
      the acute course of HUS while the two last variants to the subacute one.

PMID- 9290025
TI  - [Pathomorphology of extrarenal alterations in hemolytic-uremic syndrome in
      children].
AB  - Extrarenal alterations were studied in 64 cases of hemolytic-uremic syndrome
      (HUS) in children aged from 17 days to 4 years. Three groups are distinguished
      depending on the presence of acute renal failure (ARF) or induced by its
      treatment. Thrombotic microangiopathy which was present in the acute stage of the
      disease in the colon, pancreas, brain, spleen, liver represented the first group.
      The second group included extrarenal alterations associated with ARF
      hyperhydration of organs and tissues with accumulation of the liquid in the
      serous cavities, dilatation of the heart cavities and myocardial hypertrophy,
      brain hemorrhages, hemorrhagic diathesis, immunodepression of immunogenesis
      organs. The third group of the extrarenal alterations induced by the ARF
      treatment was characterized by infectious and iatrogenic complications.

PMID- 9290026
TI  - [Heterogeneity of pulmonary fibroblasts in tuberculosis].
AB  - Chronic inflammation and pneumofibrosis are the central events in tuberculosis
      morphogenesis. It was suggested that a certain type of fibroblasts may play a
      role in chronization of the inflammation and development of sclerosis in
      tuberculosis. Fibrous tissue from the foci of secondary tuberculosis (fibrous
      cavernous tuberculosis and tuberculomas) of 35 patients were studied light- and
      electron-microscopically and immunohistochemically. (THY 1-)fibroblasts non
      containing lipids and producing insulin-like growth factor 2 (ILGF 2), binding
      proteins 2 and 4 and epidermal growth factor receptors were found in the foci of
      secondary tuberculosis close to the granulomatous inflammation and in the new and
      scarrous fibrous connective tissue of the tuberculoma capsule and caverna walls.
      These fibroblasts are able for auto- and paracrine regulation of the
      proliferation of fibroblasts, epithelium and other cells in the inflammatory
      foci. (THY 1+) fibroblasts containing lipids were observed in the foci of old
      sclerotic changes among the rough collagen fibres. Thus, (THY 1-) fibroblasts
      probably play a key role in chronization of inflammation, proliferation and
      pretumorous dysplasia of pulmonary epithelium in secondary tuberculosis. (THY 1+)
      fibroblasts containing lipids may show more pronounced collagenesis and may
      persist under hypoxia condition in the collagenous scars for a long time.

PMID- 9290028
TI  - [Acute hemorrhagic leukoencephalitis in a woman with Goodpasture syndrome].
AB  - A case of acute leukoencephalitis in a 17-year-old female with Goodpasture
      syndrome is described. Acute leukoencephalitis is a rare inflammatory
      degenerative disease (practically not studied so far) affecting the brain white
      matter. The disease develops acutely as a rule after respiratory viral infection
      and has a fatal exitus. Multiple hemorrhages in the brain white matter with
      demyelinization and axons death are observed histologically.

PMID- 9290027
TI  - [Possible combination of eosinophilic infiltration of the stomach, small and
      large intestines with psoriasis].
AB  - The combination of the eosinophilic infiltration of the stomach, small and large
      intestine with psoriasis is described. Diarrhea and syndrome of the disturbed
      absorption in eosinophilic gastroenteritis coincided with exacerbation of the
      skin disease. Clinical regression of both conditions with disappearance of
      peripheral eosinophilia occurred simultaneously. Participation of T-cell immunity
      and IgE is suggested as a pathogenetic mechanism of eosinophilic gastroenteritis
      and psoriasis.

PMID- 9290029
TI  - [Nephropathic variant of AL-amyloidosis].
AB  - One case of a nephropathic variant of primary amyloidosis is described. Genetic
      or familial genesis of the disease is considered on the basis of anamnesis.

PMID- 9290030
TI  - [Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). Bone
      manifestations].
AB  - This is a benign disease from the group of histiocytoses with a slow progressive
      course. Bone manifestations are extranodal disease manifestations. 3 cases of the
      disease in females of 21, 42 and 49 years old with involvement of ilial, tibia
      and femur bones, respectively, are described. Lymph node changes in one patient
      arose 9 years after the bone involvement. Microscopic bone picture was similar to
      that in the lymph node. 2 patients received radiation therapy on the affected
      bone and were discharged from the hospital with the improvement and 1 patient was
      treated surgically.

PMID- 9290031
TI  - [A rare defect of esophageal development, simulating cancer].
AB  - One case of the semilunar valve of the cardial oesophageal aperture in a 86-year
      old female is described. The condition simulated carcinoma and resulted in the
      development of megaesophagus with a diverticule and forestomach formation. Colon
      diverticulosis was also observed. The complex of clinical and morphological
      manifestations characterizes this pathology as a peculiar syndrome. Syndrome of
      the semilunar aperture into the stomach with formation of the megaoesophagus,
      diverticules, forestomach and colon diverticulosis-Shmurun's syndrome.

PMID- 9290032
TI  - [Theoretical pathology of R. Virkhow and current problems and infectious diseases
      (175th anniversary of the birth of R. Virkhow)].

PMID- 9290033
TI  - [Classification, pathology and molecular biology of pituitary adenoma].
AB  - Pituitary adenomas were once considered a homogenous collection of morphologic
      entities distinguishable pathologically by differences in cytoplasmic staining
      affinities. Methodological and conceptual advances over the past decade have
      since confirmed the contrary demonstrating that pituitary adenomas are
      morphologically and biologically diverse, and that designations such as
      acidophilic, basophilic and chromophobic, beyond their descriptive merit, are
      without consistent morphologic, endocrinologic or practical significance. The
      application of electron microscopy and immunohistochemistry has brought forth a
      new classification of pituitary adenomas based on ultrastructure and hormonal
      content, updating understanding of their pathology, secretory function and
      cytogenesis. As a primary objective, current functional classification of
      pituitary tumors is discussed in detail. In addition to reviewing the morphology
      of pituitary tumors, special emphasis is also placed on the important
      clinicopathologic correlations relevant to these lesions.

PMID- 9290034
TI  - [Seventy-five years since foundation of the Pathology chair at Omsk Medical
      Academy].

PMID- 9290035
TI  - [Helicobacter pylori infection is carcinogenic for humans].
AB  - International Agency for Research on Cancer recognized as sufficient the evidence
      of Helicobacter pylori (HP) infection carcinogenicity and placed it into the 1st
      group of carcinogens. The results of the studies performed during last years are
      discussed. They showed the involvement of HP in the development of stomach
      cancer. HP enhances mitogenesis of epithelium with translocation of immature
      cells on the surface of stomach mucous membrane and thus forms the targets for
      mutagenic and carcinogenic influences. HP takes part in the formation of
      mutagens, primarily of free oxygen radicals. Achlorohydria is the outcome of HP
      gastritis and results in the bacterial growth in the stomach which participate in
      the formation of N-nitrosocompounds-well known carcinogens. Antitumor stomach
      defense is weakened by the decrease in the stomach of ascorbic acid, carotin and
      tocopherol resulting from HP-infection.

PMID- 9290036
TI  - [Epidemiological studies on the transmission of bovine spongiform encephalopathy
      (BSE)--remarks from a biometric viewpoint].
AB  - This contribution discusses biometrical aspects of the design and analysis of
      epidemiological case-control studies. The study chosen as an example was
      undertaken to investigate the transmission of bovine spongiform encephalopathy
      (BSE) to calves and the role of the inclusion of meat and bonemeal in proprietary
      feedstuffs. The hypothesis was examined by means of a case-control study which is
      summarized with emphasis on its study design and the collection of data. The
      analysis included the estimation of raw odds-ratios for the inclusion of meat and
      bonemeal in proprietary feedstuffs for calves as well as adjusted odds-ratios
      using logistic regression. This strategy is discussed and the chosen regression
      model is compared with an alternative one. Results show that problems occurred
      when recruiting herds for the study leading to uneven proportions of cases and
      controls. Because of these misproportions and due to different data quality for
      cases and controls the interpretation of the study results is difficult.

PMID- 9290037
TI  - [Significance of biotechnology in reproductive biology and veterinary medicine].
AB  - In the last decade a good number of biotechnical methods have been developed.
      They are available in medical, biological, and ecological fields of work as well
      as techniques that can replace animal experiments. These methods have been
      developed on the basis of researchwork in andrology (AI and cryoconservation of
      spermatozoa), endocrinology (hormonal control of reproduction) and the
      availability of industrial produced hormones and their analog. On the other hand
      practical clinical techniques for examination like the availability of sonography
      advice and clinical practical techniques for non-surgical recovery and
      transplantation of gamets and embryos have been the prerequisites for a
      successful work in this field of action. These fields of action are extended from
      breeding aspects (genetical progress) over the control of epidemics to the
      exportation of genetic material (especially developing countries to overcome
      hygienic and adaptation problems), the creation of gen-pools (conservation of
      breeds-species) and as well as the elimination of genetic defects like BLAD or
      DUMPS by help of PCR-techniques or the identification of positive characters like
      milk components and sexing of embryos. The industrial use of bioproducts produced
      by especially designed biosystems is in work but in Germany not possible by
      reasons of legislative restrictions. In the light of these developments the
      veterinary fields of work should be discussed and focussed towards an
      understanding that the veterinarian should be active and in a polposition in the
      processing of reproduction and production and presentation of food of animal
      origin by using these new technologies.

PMID- 9290039
TI  - [Yersinia enterocolitica serovar 2a, wb, 3:b,c biovar 5 in hares and sheep].
AB  - During the last fourty years the "hare type" of Yersinia enterocolitica was
      detected in the brown hare and other mammals in several European countries. In
      northern Germany (Province of Schleswig-Holstein) the pathogen was not found in
      the post mortem materials of the cattle, swine and horses during the years 1990
      1996. In approximately 1,000 sheep studied this yersinia was cultured from the
      internal organs of one diarrhoeic lamb. The examination of some 200 perished
      hares reveals one animal with granulomatous splenomegaly and culture of this
      pathogen. Yersinia enterocolitica is one of the pathogens causing
      pseudotuberculosis-like lesions in the hare.

PMID- 9290038
TI  - [Vaccination of pigeons against Salmonella infections].
AB  - The efficiency of the live vaccine Zoosal T with a double marker mutant of
      Salmonella Typhimurium was tested on conditioned pigeons. For challenge infection
      we used a pigeon specific variation copenhagen strain in a defined state of
      virulence. The reduction of mortality and the persistence of Salmonella in organs
      were evaluated. An oral booster enhances the protection due to vaccination.

PMID- 9290040
TI  - [Nutritional biochemical aspects of the significance, of the utilization, of
      metabolism and of the administration of vitamin E and of selenium in sheep
      (review)].
AB  - A review is given on the significance, availability, metabolism and application
      of vitamin E and selenium in sheep. Vitamin E deficiency commonly occurs in
      spring. Selenium deficiency occurs in certain areas where the selenium content of
      plants is low. A further factor is the low availability of selenium as a
      consequence of reduction reactions in the forestomachs. When the supply of
      vitamin E and selenium is suboptimal, activity of the immune system and growth
      are impaired.

PMID- 9290041
TI  - [Qualitative and quantitative kidney function testing in dogs using MAG3
      clearance].
AB  - In the presented study 99mTc-MAG3 clearance measurements were undertaken in 14
      dogs during renal scintigraphic examination. Of these dogs, 10 showed no renal
      impairment, the other 4 exhibited clinically manifested nephropathy. It was the
      aim of these examinations to determine if this type of clearance measurement that
      is routinely used in human medicine is suitable for diagnosis of canine
      nephropathy. An algorithm for the calculation of the MAG3-Clearance developed for
      humans was modified. The clearance measurement can be performed during the renal
      scintigraphic procedure without any difficulties. In the group of dogs with no
      renal impairment the clearance values ranged between 6.4 and 8.0 ml/min/kg,
      whereas in the group of patients exhibiting nephropathies the values ranged
      between 2.0 and 2.7 ml/min/kg. The suitability of the method for its use in dogs
      needs to be confirmed with higher patient numbers. In addition, further studies
      are necessary to precisely assess the correlation between measured clearance
      values and effective renal plasma flow in dogs.

PMID- 9290042
TI  - [Effects of captopril on the male reproductive organs and various semen
      parameters of rabbits].
AB  - The effect of the administration of captopril on the concentrations of Zn, Cu, Mg
      and Ca into different organs, on their histological structure and several semen
      parameters of male rabbits was studied. For 9 weeks 6.5 mgs captopril/kg b.w.
      were administered daily to 7 months old White New Zealand rabbits p.o. Semen
      samples were collected at the beginning of the experiment and after 4 and 9
      weeks. The animals were sacrificed 9 weeks after the beginning of the experiment
      and organ samples were collected for histological examination and for the
      determination of the Zn, Cu, Mg and Ca concentrations in several tissues and the
      semen samples. The absolute and relative weight of the right and left testes of
      the test animals revealed a tendency for increase. Absolute and relative weight
      of the right epididymis and the relative weight of the left epididymis were
      significantly increased. The concentration of Zn in the blood, of Cu and Ca in
      the epididymis and of Mg in the testes of the test animals were significantly
      decreased. A significant increase was observed of the Cu and Mg concentrations in
      the adrenals. In the semen Cu concentration was significantly increased 9 weeks
      after the beginning of the experiment. Mg concentration was significantly
      decreased 9 weeks as compared with 4 weeks after the beginning of the experiment.
      Histological examination of tissue specimens of brain, liver, kidney, adrenal
      glands, testes, epididymis, ductus deferens and seminal vesicles from all
      experimental animals didn't reveal any remarkable lesion under the light
      microscope. The other semen parameters like volume, motility, sperm number and
      morphology had not changed. As the values of alcalic and acid phosphatase and
      ASAT in the semen samples showed many variations, statistical analysis could not
      be performed.

PMID- 9290043
TI  - [Comparison of the results from commercially available Brucella ELISA test kits
      for the investigation of bovine sera].
AB  - Bovine sera from a farm with bacteriologically confirmed brucellosis were taken
      for comparative serological studies using conventional methods (slow
      agglutination test--SAT, complement fixation test--CFT, Rose-Bengal-plate
      agglutination-test--RBPT) and 5 different commercially available brucellosis
      ELISA testkits. These serum samples together with other infectious sera producing
      low level positive antibody titers in conventional tests did not react uniformly
      when tested by five different commercial ELISA testkits. The introduction of a
      standard control serum with a general cut-off resulted in a greater uniformity of
      ELISA results from 4 of 5 ELISA testkits and a closer approach to results of the
      CFT which is regarded as the confirmatory test for brucellosis. This control
      serum, on the other hand, was not suitable for the identification of the
      sensitivity of the various ELISA test kits. For this purpose, in SAT and CFT
      weakly positive reacting brucella sera from infected farms is needed.

PMID- 9290044
TI  - [Present problems in detection of sources of infection and chains of infection
      with enterohemorrhagic E. coli (EHEC)].
AB  - In the context of the detection of the haemolyticuraemic syndrome (HUS) and of
      enterohaemorrhagic E. coli (EHEC) in 13 persons, 372 faeces samples from 13 herds
      of cattle in northern Bavaria were examined for the presence of EHEC. 128 (34.4%)
      of the faeces samples were found to be VT-positive. From 78 of these samples
      (61%), verotoxin-producing E. coli strains (VTEC) could be isolated. During these
      examinations, E. coli strains with combinations of markers (VT, eae A, EHEC
      haemolysin) being typical of EHEC were found in 3 samples from animals belonging
      to the same herd. In 2 cases, these could be assigned to O157:H-, in one, to
      O118:H16. It has not been possible to detect possible sources of infection and
      chains of infection assumed to exist in association with the detection of HUS and
      EHEC infections in humans because most cases had been diagnosed on the basis of
      verotoxin detection in stool specimens. Moreover, corresponding isolates for a
      comparative onward differentiation from verotoxin-producing E. coli isolates from
      animals were not or could not be made available.

PMID- 9290045
TI  - [Integration of young goats into a herd of adult goats].
AB  - The female offsprings of a goat farm were observed to establish what effects the
      introduction of these goats to the older animals has on behaviour, physical
      development, fertility and milk yield. The 32 young goats were divided into two
      groups. Shortly after group 1 had been mounted, they were introduced to the older
      goats. From group 2 those who had already given birth were introduced to the
      older goats the following spring. The following results could be ascertained: In
      group 1 there were significantly more twin births and the weight of the newborn
      kids was greater than that of group 2. The weight gain of the two groups differed
      only marginally. This was also the case for the milk yield. After having
      integrated them into the herd of older goats, the young goats developed a
      strategy for avoiding, to a large extent, being pursued by older goats and to
      achieve almost undisturbed fodder intake. Amongst the young goats there is a
      marked sense of group cohesion. When the shed is well structured, a useable area
      of 1.2 m2/animal for hornless goats seems to be enough to ensure species specific
      husbandry conditions.

PMID- 9290046
TI  - [Contribution to therapy of the "prostate syndrome" in aged dogs].
AB  - The treatment of the "prostate syndrome" is a great challenge for the practicing
      veterinarian. In the present paper the therapeutic approach of this syndrome will
      be evaluated. 58 older dogs showing this syndrome were castrated and received
      thereafter oral antibiotic therapy. For further additional treatment the dogs
      were assigned to two groups. The groups were treated as follows: Group one: 41
      dogs were treated with retard Gestagen and Flumethason infiltrated into the
      prostate gland tissue. Group two: 17 dogs were treated with a single
      subcutaneously applied Gestagen injection. The success of the therapy was judged
      by decrease the size of the prostate gland to normal size. The first evaluation
      took place after 2 weeks and the second one after a year following castration and
      treatment. At the time of the first judgement 95.1% of the dogs in the group one
      and 70.6% in the group two showed normal prostate gland size. At the time of the
      second examination, a year after the treatment still 82.8% of the dogs in the
      group one and only 52.8% in the group two showed normal prostate gland size.
      These results suggest that the infiltration of the enlarged prostate gland with
      retard acting Gestagen and Flumethason results in long lasting diminishing of
      size of the diseased gland.

PMID- 9290047
TI  - [Helminth infection of slaughtered sheep in Upper Bavaria. 3. Distribution of
      colonization of nematodes in the large intestine of sheep].
AB  - The distribution of Chabertia (Ch.) ovina, Oesophagostomum (O.) venulosum and
      Trichuris spp. within the large intestine of naturally infected sheep in the
      dependence of worm counts and the presence of nematodes of other species or
      genera was evaluated. The large intestine was divided into 4 sections. More than
      75% of Ch. ovina were found within the disk-like section of the colon
      independently from worm count and presence of nematodes of other species. O.
      venulosum and Trichuris spp. preferred the caecum and the first section of the
      colon up to the beginning of the disk-like section. In both, the share of worms
      recovered from the first section of the colon did increase with higher worm
      counts. The simultaneous presence of O. venulosum and Trichuris spp. had a
      significantly negative influence on the share of Trichuris spp. isolated from the
      caecum.

PMID- 9290049
TI  - Carnitine palmitoyltransferase and acyl-coA binding protein: two more players in
      the membrane phospholipid fatty acid turnover of human red cells?

PMID- 9290050
TI  - [Biologically active peptide fragments of functional proteins produced by
      proteolysis in vitro].
AB  - Over 100 various peptides were identified as a result of numerous studies of in
      vitro proteolytic digestion of some proteins and tissue preparations. Many of
      them exhibit wide spectra of biological effects, which are similar to those
      described for some groups of endogenous peptide bioregulators. The possibility of
      in vitro modeling of endogenous processes of proteolytic digestion of proteins
      that provides biologically active peptides is discussed.

PMID- 9290048
TI  - Decreased secretion of very-low-density lipoprotein triacylglycerol and
      apolipoprotein B is associated with decreased intracellular triacylglycerol
      lipolysis in hepatocytes derived from rats fed orotic acid or n-3 fatty acids.
AB  - Hepatocytes from rats fed a chow (control) diet or from rats fed a chow diet
      supplemented with either orotic acid (OA; 1%, w/w) or fish oil (FO; 20%, v/w)
      were maintained in culture for periods up to 48 h. during the first 24 h period,
      the low rates of output of very-low-density lipoprotein (VLDL)-associated
      triacylglycerol (TAG) and apolipoprotein B (apoB) in hepatocytes from the FO- and
      OA-fed animals were associated with significantly lower rates of intracellular
      TAG lipolysis and re-esterification. Most of the VLDL TAG secreted was mobilized
      via lipolysis of the intracellular TAG pool, but the proportion of VLDL TAG
      secreted via this route in cells from the FO-fed and OA-fed animals was decreased
      compared with that in the control-fed animals' cells. In the presence of
      exogenous oleate the inhibitory effect of OA feeding on VLDL apoB and TAG
      secretion persisted in the derived hepatocytes for up to 48 h following
      isolation. However, when oleate was absent no inhibitory effect on the secretion
      of TAG and apoB was observed between 24 and 48 h. Under these conditions the rate
      of intracellular TAG turnover returned to normal. The initial inhibitory effect
      of FO feeding on VLDL TAG and apoB secretion did not persist in the derived
      hepatocytes between 24 h and 48 h of culture in the presence of exogenous oleate.
      Although intracellular TAG lipolysis and VLDL TAG and apoB secretion rates appear
      to be positively correlated, a causal relationship has not been conclusively
      established.

PMID- 9290051
TI  - [Non-natural aglycones of glycopeptide antibiotics of the vancomycin group.
      Synthesis and antibacterial activity].
AB  - A new approach for the modification of the heptapeptide core of glycopeptide
      antibiotics was proposed based on the replacement of amino acid residues in
      positions 1 and 3 in teicoplanin aglycone and in position 1 in the eremomycin
      aglycone. Six novel nonnatural aglycones of the vancomycin type were obtained.
      Compounds derived from the teicoplanin aglycone exhibited in vitro activity
      against Gram-positive bacteria, and two of them were also active against the
      vancomycin-resistant enterococci.

PMID- 9290052
TI  - [Interaction of anti-TNF-alpha monoclonal antibodies E7H2 with mutant and hybrid
      proteins].
AB  - A number of hybrid proteins containing amino acid sequences of human lymphotoxin
      and human and mouse tumor necrosis factors were obtained by means of genetic
      engineering. By using these proteins, an antigenic determinant in the molecule of
      human tumor necrosis factor for monoclonal antibodies E7H2 (MAb E7H2), previously
      developed against this factor was localized. It was demonstrated by Western blot
      analysis that the MAb E7H2-binding site is located in the sequence region 37-49
      of human tumor necrosis factor and includes the sequence Val41GluLeuArg44
      directly interacting with MAb E7H2.

PMID- 9290053
TI  - [Structural characteristics of four long terminal repeats (LTR) of human
      endogenous retroviruses and features of their integration sites].
AB  - Four LTR-containing regions of human chromosome 19 were sequenced by the primer
      walking technique using strings of short oligonucleotides tightly bound to the
      template. A comparative and evolutionary analysis of sequences homologous to
      human endogenous retroviruses (HERV) was performed, and the prototypes of the
      LTRs were determined. Analysis of the chromosome 19 sequences adjacent to LTR
      revealed that LTRs of HERV-K share a common location with other retroposons.

PMID- 9290054
TI  - [Molecular cloning and characterization of cDNA of the rpc10+ gene encoding the
      smallest subunit of nuclear RNA polymerases of Schizosaccharomyces pombe].
AB  - The full-length cDNA of the rpc10+ gene encoding mini-subunit Rpc10, which is
      common for all three nuclear RNA polymerases of the fission yeast
      Schizosaccharomyces pombe, was cloned and sequenced. The Rpc10 subunit of Sz.
      pombe and its homologs from S. cerevisiae and H. sapiens are positively charged
      proteins with a highly conserved C-terminal region and an invariant zinc-binding
      domain (Zn-finger) of a typical amino acid composition: YxCx2Cx12RCx2CGxR.
      Functional tests of heterospecific complementation, using tetrad analysis or
      plasmid shuffling, showed that the Rpc10 subunit of Sz. pombe can successfully
      replace the homologous ABC10 alpha subunit in nuclear RNA polymerases I-III of S.
      cerevisiae.

PMID- 9290055
TI  - Atherosclerosis and pentoxifylline. Proceedings of an international symposium.
      Prague, 10-12 October 1996.

PMID- 9290058
TI  - Ibuprofen inhibits arylamine N-acetyltransferase activity in the bacteria
      Klebsiella pneumoniae.
AB  - Ibuprofen, one of the nonsteroidal anti-inflammatory drugs, inhibited arylamine N
      acetyltransferase activity of Klebsiella pneumoniae both in vitro and in vivo.
      The NAT activities of Klebsiella pneumoniae were inhibited by ibuprofen in a dose
      dependent manner both in vitro and in vivo. In vitro, the NAT activity was 0.675
      +/- 0.028 nmol/min/mg of protein for the acetylation of 2-aminofluorene. In the
      presence of 8 mM ibuprofen, the NAT activity was 0.506 +/- 0.002 nmol/min/mg of
      protein for the acetylation of 2-aminofluorene. In vivo, the NAT activity was
      0.279 +/- 0.016 nmol/min/10(10) colony forming units (CFU) for the acetylation of
      2-aminofluorene. In the presence of 8 mM ibuprofen, the NAT activity was 0.228 +/
      0.008 nmol/min/10(10) CFU for the acetylation of 2-aminofluorene. The inhibition
      of NAT activity by ibuprofen was shown to persist for at least 4 h. For in vitro
      examination, the values of apparent Km and Vmax were 1.08 +/- 0.05 mM and 9.17 +/
      0.11 nmol/min/mg of protein, respectively, for 2-aminofluorene. However, when 8
      mM of ibuprofen was added to the reaction mixtures, the values of apparent Km and
      Vmax were 1.19 +/- 0.01 mM and 6.67 +/- 0.11 nmol/min/mg of protein,
      respectively, for 2-aminofluorene. For in vivo examination, the values of
      apparent Km and Vmax were 1.24 +/- 0.48 mM and 4.18 +/- 1.06 nmol/min/10 x 10(10)
      CFU, respectively, for 2-aminofluorene. However, when 8 mM of ibuprofen was added
      to the culture, the values of apparent Km and Vmax were 0.95 +/- 0.29 mM and 2.77
      +/- 0.37 nmol/min/mg protein, respectively, for 2-aminofluorene, respectively.
      This report is the first finding of ibuprofen inhibition of arylamine N
      acetyltransferase activity in a strain of Klebsiella pneumoniae.

PMID- 9290059
TI  - Formate hydrogenlyase is needed for proton-potassium exchange through the F0F1
      ATPase and the TrkA system in anaerobically grown and glycolysing Escherichia
      coli.
AB  - Anaerobically grown and glycolysing Escherichia coli produced H2 and carried out
      H+-K+-exchange in two steps, the first of which had the fixed stoichiometry for
      DCCD-sensitive fluxes (2H+/K+), and the second one had a variable stoichiometry
      for DCCD-sensitive fluxes. H2 production and the 2H+/K+-exchange were lost in the
      DeltafdhF or DeltahycA-H mutant. In the DeltafdhF mutant, H+-K+-exchange with Km
      for K+-uptake of 2.3 mM and less K+-gradient between the cytoplasm and the medium
      were observed. H2 production and H+-K+-exchange with a high Km for K+-uptake were
      carried out in the uncD mutant; however, both H2 production and H+-K+-exchange
      were lost in the Deltaunc or uncE mutant. H2 production was observed in the trkA
      trkD kdpA mutant. It was displayed in protoplasts with increased membrane
      permeability when donor or acceptor of reducing equivalents-formate with DTT or
      NADH respectively-was added. The F0F1 and the TrkA(H) or the F0 and the TrkA(G)
      had been assumed to form the united supercomplexes, functioning as a H+-K+-pump
      or antiporter respectively (for review see Bioelectrochem Bioenerg 33:1, 1994).
      Results allow the proposal that H2 production by FHL has a relationship with the
      H+-K+-exchange through a H+-K+-pump and via an H+-K+-antiporter. Formate and NADH
      can serve as a donor and an acceptor of reducing equivalent respectively, for
      operation of such supercomplexes.

PMID- 9290060
TI  - Molecular characterization of the clusters of genes encoding the botulinum
      neurotoxin complex in clostridium botulinum (Clostridium argentinense) type G and
      nonproteolytic Clostridium botulinum type B.
AB  - The cluster of genes encoding components of the progenitor botulinum neurotoxin
      complex has been mapped and cloned in Clostridium botulinum type G strain ATCC
      27322. Determination of the nucleotide sequence of the region has revealed open
      reading frames encoding nontoxic components of the complex, upstream of the gene
      encoding BoNT/G (botG). The arrangement of these genes differs from that in
      strains of other antigenic toxin types. Immediately upstream of botG lies a gene
      encoding a protein of 1198 amino acids, which shows homology with the nontoxic
      nonhemagglutinin (NTNH) component of the progenitor complex. Further upstream
      there are genes encoding proteins with homology to hemagglutinin components (HA
      17, HA-70) and a putative positive regulator of gene expression (P-21). Sequence
      comparison has shown that BoNT/G has highest homology with BoNT/B. The sequence
      of the BoNT-cluster of genes in non-proteolytic C. botulinum type B strain Eklund
      17B has been extended to include the complete NTNH and HA-17, and partial HA-70
      gene sequences. Comparison of NTNH/G with other NTNHs reveals that it shows
      highest homology with NTNH/B consistent with the genealogical affinity shown
      between BoNT/G and BoNT/B genes.

PMID- 9290062
TI  - Cellobiose and cellodextrin metabolism by the ruminal bacterium Ruminococcus
      albus.
AB  - Ruminococcus albus is an important fibrolytic bacterium in the rumen. Cellobiose
      is metabolized by this organism via hydrolytic and well as phosphorylytic
      enzymes, but the relative contributions of each pathway were not clear. The
      cellobiose consumption rate by exponentially growing cells was less than that of
      crude extracts (75 versus 243 nmol/min/mg protein). Cellobiose phosphorolytic
      cleavage was much greater than hydrolytic activity (179 versus 19 nmol/min/mg
      protein) indicating that phosphorylases were key enzymes in the initial
      metabolism of the soluble products of cellulose degradation. Cellodextrin
      phosphorylase appeared to be active against substrates as large as cellohexaose.
      Phosphorylase activities were cytoplasmic, but hydrolytic activities were
      associated with both the membrane and cytoplasmic fractions. Free glucose was
      phosphorylated with a GTP-dependent glucokinase, and this enzyme showed 20-fold
      higher activity with GTP or ITP (>324 nmol/min/mg protein) than with ATP, UTP,
      CTP, GDP, or PEP. The activity was decreased at least 57% when mannose, 2
      deoxyglucose, or fructose was used as substrate compared with glucose. The Kms
      for glucose and GTP were 321 and 247 microM, respectively. Since phosphorolytic
      cleavage conserves more metabolic energy than simple hydrolysis, it is likely
      that such pathways provide for more efficient growth of R. albus in substrate
      limiting conditions like those found in the rumen.

PMID- 9290063
TI  - A gene encoding an exo-beta-glucosidase from Cellvibrio mixtus.
AB  - Cellvibrio mixtus produces an array of endohydrolytic enzymes involved in the
      initial phases of beta-glycan polysaccharide degradation in the soil. These
      enzymes convert complex, high-molecular-weight, insoluble polysaccharides into
      low-molecular-weight, soluble oligosaccharides which must be further degraded for
      cellular uptake and catabolism. Little is known about the enzymes involved in
      this latter process in C. mixtus. In this paper we report the cloning of the lam2
      gene, which encodes an exohydrolase of low-molecular-weight, soluble beta-glucans
      and which may be involved in the latter stages of beta-glucan degradation in C.
      mixtus. The Lam2 enzyme has a broad substrate specificity including beta-1,3-,
      beta-1,4-, beta-1,6-, and beta-1,3-1,4-linked glucans. Analysis of the end
      products of laminarin hydrolysis showed that the Lam2 enzyme is an exohydrolase
      that removes terminal glucose residues from its substrate. The substrate
      specificity and action pattern of this enzyme indicate that it belongs to
      EC3.2.1.21 (beta-glucosidase). The 2.5-kb lam2 insert encodes a protein of
      approximately 91 kDa as determined by in vivo transcription/translation and
      deletion analyses. Southern analysis showed that a single copy of the gene exists
      on the C. mixtus chromosome.

PMID- 9290065
TI  - Molecular characterization of genes encoding a novel ABC transporter in
      Thermoanaerobacterium thermosulfurigenes EM1.
AB  - The nucleotide sequence of two open reading frames (ORFs) from
      Thermoanaerobacterium thermosulfurigenes EM1 was determined that encode proteins
      with similarity to components of ATP-binding cassette (ABC) transport systems.
      Sequence analysis suggests that the deduced proteins AbcA and AbcB consist of an
      NH2-terminal membrane-spanning domain and a COOH-terminal ATP-binding domain. The
      deduced proteins AbcA and AbcB showed highest similarity to proteins of the MsbA
      subfamily of ABC transporters. AbcA and AbcB probably function as a heterodimer.
      An ORF predicted to encode the primary sigma factor SigA was identified
      downstream of abcB.

PMID- 9290066
TI  - Sequence analysis of Spiroplasma phoeniceum and Spiroplasma kunkelii spiralin
      genes and comparison with other spiralin genes.
AB  - The spiralin genes from two phytopathogenic spiroplasmas, Spiroplasma phoeniceum
      and Spiroplasma kunkelii, were amplified by PCR, cloned, and sequenced.
      Comparison of the amino acid sequences of the five spiralins analyzed to date
      confirm that the spiralins have a general amphiphilic character and possess a
      conserved lipoprotein signal peptide. It also shows that a conserved central
      region and an amino acid repetition, including a VTKXE consensus sequence, are
      present in all spiralins analyzed.

PMID- 9290067
TI  - Phylogenetic and narG analysis of a Hyphomicrobium isolate.
AB  - An obligately methylotrophic organism was isolated from a water well that
      manifested symptoms of biofouling. The isolate was appendaged and utilized
      methylamine, dimethylamine, trimethylamine, or methanol as the sole carbon and
      energy source. The isolate exhibited hydroxypyruvate reductase activity,
      suggesting C1-assimilation via the serine pathway. Fatty acid profiling indicated
      the predominance of 18:1 cis-fatty acids. The isolate did not grow anaerobically
      with nitrate as the final electron acceptor. Genomic DNA from the isolate did not
      hybridize against the narG gene, which encodes the alpha subunit of dissimilatory
      nitrate reductase in Escherichia coli. The phenotypic data suggested the
      assignment of the isolate to the genus Hyphomicrobium. The identification was
      supported by phylogenetic characterization based on 16S rRNA sequence comparisons
      of the isolate.

PMID- 9290068
TI  - Enzyme-linked lectinsorbent assay measures N-acetyl-D-glucosamine in matrix of
      biofilm produced by Staphylococcus epidermidis.
AB  - An enzyme-linked lectinsorbent assay (ELLA) was developed for quantification of
      in situ biofilm produced by Staphylococcus epidermidis in polystyrene 96-well
      tissue culture plates with phosphatase-labeled wheat germ agglutinin (WGA) as a
      specific probe for the GlcNAcbeta-1,4n component of exocellular matrix material
      (EMM) that is responsible for intercellular adhesion and accumulation. The ELLA
      and the modified Christensen dye assay were used to test 13 laboratory strains of
      coagulase-negative staphylococci and 10 clinical isolates of S. epidermidis. Four
      biofilm-positive laboratory strains of S. epidermidis were positive by both
      tests, and six biofilm-negative strains were negative by both. One strain of S.
      hemolyticus was positive by the ELLA only. Two of the 10 clinical isolates of S.
      epidermidis were positive by both assays, two were negative by both, and the
      remaining were positive by the ELLA only. The ELLA was objective, reproducible,
      specific, sensitive, and useful for screening strains for their capacity to
      adhere to plastic, produce EMM, and form biofilm.

PMID- 9290069
TI  - The influence of EDTMP-concentration on the biodistribution of radio-lanthanides
      and 225-Ac in tumor-bearing mice. The ISOLDE Collaboration.
AB  - High-resolution gamma spectroscopy was applied to measure simultaneously the
      biodistribution of carrier-free radionuclides of several lanthanides (141Ce,
      145Sm, 149Gd, 167Tm) and 225Ac in tumor-bearing nude mice. Mixtures of the
      radiotracers were injected in solutions containing different concentrations of
      EDTMP (ethylenediaminetetramethylenephosphonic acid). The strong dependence of
      liver uptake on the ionic radius of the radio-lanthanides was confirmed for all
      tracers used. The ratios of radioactivity concentrated in tumour that
      concentrated in liver are strongly influenced by the EDTMP concentration,
      reaching values close to 10 for Tm, 3 for Sm, and 1 for Ac. The optimal EDTMP
      concentrations, giving highest tumor-to-liver ratios of enrichment, were between
      1 and 10 mM for 100 microL injected volume for the animal model used in this
      experiment. In radionuclide therapy using EDTMP as ligands, close control of
      ligand concentration will be necessary.

PMID- 9290070
TI  - Radioiodinated N-(alkylaminoalkyl)-substituted 4-methoxy-, 4-hydroxy-, and 4
      aminobenzamides: biological investigations for the improvement of melanoma
      imaging agents.
AB  - The syntheses and radiolabelling of 27 new N-(alkylaminoalkyl)-4-methoxy-, -4
      hydroxy-, and -4-aminobenzamides are described and evaluated in C57B1/6 mice with
      subcutaneously transplanted B16 melanoma in order to screen the optimal chemical
      structure for melanoma scintigraphy. Using T1(TFA)3 for 131I- labelling, a series
      of radioiodinated 4-methoxy benzamide derivatives proved to exhibit superior
      melanoma uptake with outstanding melanoma/non-target-tissue ratios. From the
      benzamide derivatives tested, N-(2-(1'-piperidinyl)ethyl-3-[131I]iodo-4
      methoxybenzamide and N-(2-diethylaminoethyl)-3-[131I]iodo-4-methoxybenzamide
      demonstrated best results. The introduction of 4-hydroxy and 4-amino groups led
      to less favourable benzamides. While the former compounds showed little melanoma
      uptake, the latter revealed unfavourable melanoma/non-target-tissue ratios.
      Additionally, it could be shown that an amino group was inevitably necessary for
      melanoma uptake, and that dialkylation of the amide nitrogen and replacing CONH
      by CH2NH revealed less advantageous results.

PMID- 9290071
TI  - Synthesis of some 11C-labelled MAO-A inhibitors and their in vivo uptake kinetics
      in rhesus monkey brain.
AB  - Five potential MAO-A inhibitors--harmine, N-methyl-harmine, harmaline,
      brofaromine, and clorgyline--were labelled with 11C and their brain kinetics
      evaluated in vivo in rhesus monkey using PET. The compounds were synthesized by
      alkylation with 11C methyl iodide and obtained in 48-89% radiochemical yield
      within 40 to 45 min synthesis time and with specific radioactivities in the
      region of 0.49-2.4 Ci mumol-1 (18-87 GBq mumol-1) at the end of synthesis. The
      kinetic pattern after administration of MAO-A inhibitors was comparable to that
      seen in the tracer study when using 11C-brofaromine, 11C-harmaline, or 11C
      clorgyline, although the magnitude of uptake markedly increased in the case of
      brofaromine and harmaline. Both 11C-methylharmine and 11C-harmine showed a
      significant washout in the inhibition studies. The kinetics of brain uptake with
      and without MAO-A inhibition is compatible with a significant fraction of the
      tracer bound to MAO-A for 11C-methylharmine and 11C-harmine, whereas 11C
      brofaromine, 11C-harmaline, or 11C-clorgyline did not seem to show specific
      enzyme binding.

PMID- 9290073
TI  - The prediction of the structure of technician (V) complexes using density
      functional techniques.
AB  - Electronic structure calculations using the local-density functional method were
      shown to accurately reproduce the geometry of five oxo-Tc (V)-based
      radiopharmaceuticals containing a variety of donor ligands. Calculations were
      performed using the DGauss program on a Cray C90 supercomputer, requiring
      approximately 40 CPU h for each molecule. The predicted bond lengths were within
      +/- 0.04 A of the crystallographic coordinates, and bond angles within +/- 4
      degrees. Root mean square (RMS) deviations between the predicted and
      crystallographic coordinates were less than 0.06, and visual inspection
      demonstrated nearly perfectly superimpossible structures.

PMID- 9290072
TI  - Autoradiographic comparison of [125I]epidepride and [125I]NCQ 298 binding to
      human brain extrastriated dopamine receptors.
AB  - Extrastriatal D2-dopamine receptors can be visualised in the monkey and human
      brain using the benzamides [11C]- and [76Br]FLB 457 in PET and [123I]epidepride
      in SPECT but not with the salicylamide analogues [76Br]FLB 463 and [123I]NCQ 298.
      To clarify the background for the differences in binding seen in vivo, we have
      compared the in vitro binding of [125I]epidepride and [123I]NCQ 298, using human
      whole hemisphere autoradiography. The images obtained with any radioligand showed
      detailed distribution with very dense binding in the putamen and the caudate
      nucleus and with the same detailed extrastriatal distribution. Thus, the
      divergent results obtained in vivo cannot be explained by different binding
      properties of the extrastriatal receptors.

PMID- 9290074
TI  - Radioiodinated alpha-p-iodophenyl-N-tert-butylnitrone as a radical detecting
      agent in vivo.
AB  - For in vivo detection of unstable radical species, a novel radioiodinated radical
      trapping agent, alpha-p-iodophenyl-N-tert-butylnitrone (IPBN), was designed based
      on the plausible characteristics of alpha-p-hydroxy-m-iodophenyl-N-tert
      butylnitrone (HIPBN). Both compounds are iodinated analogs of alpha-phenyl-N-tert
      butylnitrone (PBN), but the latter showed low stability in vivo. The present
      compound IPBN was easily prepared and labeled with radioiodine. It showed very
      stable characteristics in vitro as well as in vivo, but was easily metabolized
      and retained at sites of superoxide production.

PMID- 9290076
TI  - Analysis of radiation dose-response curve obtained with cytokinesis block
      micronucleus assay.
AB  - The frequency of micronuclei and acentrics obtained with different doses of 60Co
      gamma radiation was examined. When compared to acentric frequency the micronuclei
      frequency was found to be higher at about 115% for doses below 1 Gy. However, it
      dropped to about 65% as the dose was increased to 4 Gy. This paper discusses the
      causes for the reduced frequency of micronuclei at higher doses by taking into
      account the possibility of their being masked from view by the daughter nuclei in
      the binucleated cell.

PMID- 9290075
TI  - N-methylquipazine: carbon-11 labelling of the 5-HT3 agonist and in vivo
      evaluation of its biodistribution using PET.
AB  - N-Methylquipazine (2-[1-(4-methyl)-piperazinyl)quinoline)) was labelled with
      carbon-11 by reacting [11C]methyl iodide with the nor-compound, quipazine.
      Radiochemical conversions were 79 +/- 7%, based on the alkylating agent. The
      total synthesis time including purification was 40 to 45 min. N-[Methyl
      11C]methylquipazine thus synthesized was >99% radiochemically pure, and the
      specific activity ranged between 12-37 GBq/mumol. Dynamic imaging with PET was
      used to examine in vivo its distribution in rat and monkey. In rat the organ
      uptake at intermediate times was: liver > heart > whole brain > or = lung >
      extracerebral tissue. Brain uptake and wash-out were rapid: A maximum was reached
      in 2 to 3 min with subsequent decrease to approximately equal to 50% the peak
      value by 13 min. In monkey the tracer uptake was heterogeneous and high in
      regions known to contain 5-HT3 receptors but also in regions devoid of these
      receptors. Tissue kinetics were similar for all regions (initial rapid
      accumulation with tmax < or = 7 min, followed by slow decrease with all regions
      approaching the level of the cerebellum at 30 to 35 min). Pretreating with
      quipazine significantly decreased only the ratio of uptake in the medulla
      oblongata compared to the cerebellum. Although the nonspecificity of its binding
      limits the usefulness of N-[methyl-11C]methylquipazine, both its kinetic behavior
      and the blocking results indicate that a more selective arylpiperazine might
      prove to be a more attractive tracer for PET studies of 5-HT3 receptors.

PMID- 9290077
TI  - Biodistribution and metabolism of [N-methyl-11C]m-hydroxyephedrine in the rat.
AB  - Biodistribution and metabolism of [N-methyl-11C]m-hydroxyephedrine ([11C]mHED),
      an analogue of noradrenaline, were assessed in rats. Pretreatment with
      desipramine, an uptake blocker, reduced uptake of radioactivity in myocardium but
      not in lung, liver, kidney, and muscle. Brain uptake was negligible. HPLC showed
      six radioactive metabolites in plasma and liver but none in myocardium. Co
      injection of unlabelled mHED or metaraminol with [11C]mHED demonstrated no
      difference between the in vivo binding potentials for mHED and metaraminol in
      myocardium.

PMID- 9290078
TI  - Preparation and use of NHS-MAG3 for technetium-99m labeling of DNA.
AB  - The chelator mercaptoacetylglycylglycylglycine (MAG3) is on of several
      amidothiols that have been used successfully to radiolabeled proteins and other
      molecules with 99mTc. Prior to radiolabeling, the sulfur in these amidothiols is
      usually protected by a benzoyl group (i.e. S-benzoyl MAG3) which requires extreme
      alkaline pH or boiling water temperatures for rapid deprotection. As a result,
      the benzoyl-protected chelator is radiolabeled prior to conjugation (i.e.
      preconjugation labeling) in the case of carriers such as proteins or polypeptides
      which cannot withstand harsh conditions. We have employed a simple, two-step,
      synthesis of the N-hydroxysuccinimide ester of MAG3 in which the sulfur is
      protected with an acetyl group (i.e. S-acetyl NHS-MAG3). A single-stranded amine
      derivitized DNA was coupled with NHS-S-acetyl MAG3. Radiolabeling was
      accomplished at room temperature and neutral pH by transchelation from 99mTc
      tartrate. In comparison to labeled SHNH-DNA, the labeled MAG3-DNA was unstable to
      cysteine transchelation, however, in contrast to SHNH-DNA, no evidence for serum
      protein binding of the labeled MAG3-DNA was observed. We conclude that the S
      acetyl NHS MAG3 bifunctional chelator may prove to be an attractive alternative
      method of radiolabeling DNA and other biologically important molecules with
      99mTc.

PMID- 9290079
TI  - In vitro and in vivo properties of murine monoclonal antibody for a novel
      immature thymocyte-differentiated antigen, JL1.
AB  - JL1 is a novel thymocyte-differentiated antigen strictly confined to stage II
      immature cortical thymocytes. It is expressed in several types of leukemias and
      lymphomas. Murine anti-JL1 monoclonal antibody labeled with 131I and 99mTc showed
      60-70% of immunoreactivity and 1.4-1.9 x 10(9) L/mol of affinity constant. The
      incubation of the radiolabeled antibody with Molt-4 cells showed no evidence of
      modulation or shedding. Localization indices increased from day 3 to day 5 in
      SCID mice bearing Molt-4 cells.

PMID- 9290080
TI  - New bis(dithiocarboxylato) nitridotechnetium-99m radiopharmaceuticals for
      leucocyte labelling: in vitro and in vivo studies.
AB  - Dithiocarboxylate ligands were synthesized and characterised. New nitrido 99m
      technetium complexes were obtained with these ligands and identified by thin
      layer chromatography. The nitrido complexes were tested in vitro in whole blood
      for leucocyte labelling and the design of the ligand was optimized. Best results
      were obtained with aliphatic linear ligands, containing 9 to 11 atoms of carbon.
      The in vivo experiment failed because an inflammated area could not be visualized
      by gamma imaging, the cell labelling mechanism being probably different.

PMID- 9290081
TI  - Practical determination of organ S values for individual patients for therapy.
AB  - Radiation dose calculations using S values of a reference man can introduce
      substantial errors for individuals patients. We found that all non target sources
      can be included in the remainder of the body estimate for therapeutic
      radionuclides. A practical method to derive organ S values based on MIRD data and
      the mass of the organ and total body of individual patients is proposed.

PMID- 9290083
TI  - Evaluation of carbon-11-labelled phenoxy bridged fatty acids for studying
      myocardial fatty acid metabolism with PET.
AB  - A phenylene moiety in the chain of fatty acids was expected to impair metabolic
      degradation. Three phenoxy-containing [11C]carboxyl-labelled fatty acids were
      synthesized and evaluated in mice and an in vivo tissue distribution study. Of
      these three, 1[11C]-3-(p-dodecyloxyphenyl)propionic acid (C12C3) showed the most
      favourable uptake in the myocardium: 1.2% of the injected dose at 30 min p.i.,
      vs. 0.6% for [11C]palmitate. The metabolic stability of C12C3 and [11C]palmitate
      was assessed by determining the amount of exhaled [11C]CO2 during a 30-min
      interval after injection. It was found that the phenoxy moiety in the gamma
      position did not prevent the metabolic degradation of C12C3: After 30 min 20.7%
      of the injected dose was exhaled as [11C]CO2 vs. 12.7% for [11C]palmitate.

PMID- 9290082
TI  - Radioiodinated antibody targeting of the HER-2/neu oncoprotein.
AB  - The HER-2/neu oncogene encodes a 185 kDa phosphoglycoprotein that is
      overexpressed in breast, ovarian and other cancers. Seven monoclonal antibodies
      reactive with oncoprotein were labeled with 131I. In vitro experiments with SKOv3
      9002-18 cells determined binding affinity, internalization and degradation. The
      biodistribution of these antibodies in comparison to 125I-labeled nonspecific
      antibody was measured in athymic mice with SKOv3 9002-18 ovarian carcinoma
      xenografts. Antibody 520C9 exhibited the highest and most specific retention in
      tumor, peaking at 17.4 +/- 5.6% ID/g at 24 h.

PMID- 9290084
TI  - Preparation of yttrium-90-labeled human macroaggregated albumin for regional
      radiotherapy.
AB  - Human macroaggregated albumin (MAA), which is currently labeled with technetium
      99m (99mTc) and 99mTc-MAA, is used clinically as a pulmonary perfusion agent and
      was directly labeled with yttrium-90 (90Y)-acetate. This study evaluated whether
      90Y-MAA could be potential radiotherapeutic agent for regional radiotherapy
      against malignant tumors. MAA suspended in 0.1 M sodium acetate buffer, pH 5.8,
      was incubated with 90Y-acetate and purified in order to get rid of unstable
      binding of 90Y by electrophoresis. The radiochemical purity of 90Y-MAA in normal
      human serum was estimated by an agarose electrophoresis method and was more than
      94% over 168 h in vitro. Following the intratumoral administration of 90Y-MAA,
      the time course of tumor radioactivity and the biodistribution in nude mice
      bearing human neuroblastoma were investigated up to 168 h. More than 93% of the
      radioactivity of the injected dose was found on the subcutaneous tumor over 168
      h. The bone radioactivity was shown as 0.06 +/- 0.03% injection dose/gram tissue
      (% ID/g) (n = 5) at 24 h, 0.73 +/- 0.20% ID/g at 72 h, 0.92 +/- 0.16% ID/g at 120
      h, and 2.51 +/- 0.59% ID/g at 168 h. A slight increase in radioactivity was noted
      in the liver, kidneys, and spleen over the 168-h periods. In conclusion, 90Y-MAA
      may be a potential agent for regional radiotherapy (brachytherapy) because of the
      sufficient persistence in the tumor following an intratumoral administration.

PMID- 9290085
TI  - Synthesis of O-[11C]Acetyl CoA, O-[11C]Acetyl-L-carnitine, and L-[11C]carnitine
      labelled in specific positions, applied in PET studies on rhesus monkey.
AB  - The syntheses of L-carnitine, O-acetyl CoA, and O-acetyl-L-carnitine labelled
      with 11C at the 1- or 2-position of the acetyl group or the N-methyl position of
      carnitine, using the enzymes acetyl CoA synthetase and carnitine
      acetyltransferase, are described. With a total synthesis time of 45 min, O-[1
      11C]acetyl CoA and O-[2[11C]acetyl CoA was obtained in 60-70% decay-corrected
      radiochemical yield, and O-[1-11C]acetyl-L-carnitine and O-[2-11C] acetyl-L
      carnitine in 70-80% yield, based on [1-11C]acetate or [2-11C]acetate,
      respectively. By an N-methylation reaction with [11C]methyl iodide, L-[methyl
      11C]carnitine was obtained within 30 min, and O-acetyl-L-[methyl-11C]carnitine
      within 40 min, giving a decay-corrected radiochemical yield of 60% and 40-50%,
      respectively, based on [11C]methyl iodide. Initial data of the kinetics of the
      different 11C-labelled L-carnitine and acetyl-L-carnitines in renal cortex of
      anaesthetized monkey (Macaca mulatta) are presented.

PMID- 9290086
TI  - Faster and easier radiochemical purity testing for [125I]sodium iothalamate.
AB  - A previous method for determination of the radiochemical purity (RCP) value of
      [125I]sodium iothalamate uses two paper strips and solvents (total developing
      time is approximately 2.5 h). To simplify and shorten the RCP testing procedure,
      our laboratory has developed a single-strip chromatography method that not only
      distributes free 125I and [125I]sodium iothalamate to different relative front
      (Rf) locations, but is also faster and easier to perform. RCP of [125I]sodium
      iothalamate was determined with the use of a 10-cm instant thin-layer
      chromatography strip impregnated with polysilicic acid gel (ITLC-SA) as the solid
      phase, and a mobile phase of 2-butanol:acetic acid:water (140:2.5:70, v/v). By
      using autoradiography and counting the strip segments in a gamma counter, our
      results indicated that free 125I migrated to Rf = 0.89-1.00 while the
      [125I]sodium iothalamate moved to Rf = 0.44-0.67. The total developing time for
      the single-strip ITLC-SA system was approximately 1 h.

PMID- 9290089
TI  - Electrolyte composition of human breast milk beyond the early postpartum period.
AB  - The electrolyte composition of breast milk beyond 6 months postpartum has not
      been extensively examined, particularly chloride concentrations. A total of 140
      samples of breast milk from 30 breast-feeding mothers were collected and
      analyzed. Mean mother's values +/- standard error of sodium (141 +/- 17 mg/L),
      potassium (480 +/- 11 mg/L), and chloride (452 +/- 32 mg/L) were found to be
      stable after 4 months postpartum until weaning commenced. Considerable
      variability was found for each constituent, equally divided between intra
      individual and inter-individual for chloride and potassium, and predominantly
      intra-individual for sodium and lactose. In light of reported nutritional
      deficiency states involving electrolytes in exclusively breast-fed infants, it is
      possible that the variability of breast milk electrolyte concentrations may
      adversely affect infant nutrition in selected cases of older exclusively breast
      fed infants.

PMID- 9290087
TI  - Cytokines and cachexia.
AB  - Prolonged production of cytokines associated with cancer and chronic infections,
      and other long-term immune reactions is increasingly recognized as a main causal
      factor of the often severe signs and symptoms that accompany these diseases:
      weight loss, anorexia, and metabolic breakdown termed cachexia. The cytokine that
      initially was held responsible for causing these changes was tumor necrosis
      factor (TNF). However, from various studies it has become clear that the action
      of TNF can only be understood in the context of simultaneous presence of other
      cytokines, some of which have activities that are at the least equally important
      as TNF in bringing about cachexia. This review summarizes the experimental
      evidence for the involvement of cytokines in the pathogenesis of cachexia.
      Indirect evidence comes from the observation that cachexia can be induced in
      animals by repeated injections of cytokines or by inoculation of cytokine
      producing cells. Thus, cachexia has been described in mice inoculated with tumor
      cells carrying and expressing genes for either TNF, interleukin-6 (IL-6),
      leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF) and
      interferon-gamma (IFN-gamma). More direct evidence is provided by the
      observations that cachexia in experimental animal models can be mitigated by
      administration of specific antagonists of cytokines. These latter type of studies
      revealed that cachexia can rarely, if ever, be attributed to one single cytokine
      but rather to a set of cytokines that work in concert in cachexia. A pool of
      anticytokine antibodies or other cytokine inhibitors might, therefore, be
      considered as a potential intervention for the treatment of cachectic patients,
      but this approach may induce immunosuppression, and, therefore, danger exists
      that such treatment may benefit the infectious agent or tumor.

PMID- 9290088
TI  - Skin content of 7-dehydrocholesterol in patients with malabsorption.
AB  - The mechanism for the development of vitamin D deficiency in patients with
      malabsorption remains unclear. We wished to examine the hypothesis that one
      factor was a reduced skin content of 7-dehydrocholesterol, the precursor for the
      formation of vitamin D in the presence of ultraviolet radiation. We measured 7
      dehydrocholesterol in skin samples from 9 patients who had previously had vitamin
      D deficiency due to malabsorption (6 with Crohn's disease, 2 with primary biliary
      cirrhosis, and 1 with idiopathic pseudo-obstruction). We found no evidence of
      reduced levels of 7-dehydrocholesterol in the skin in these patients. Lack of 7
      dehydrocholesterol does not contribute to vitamin D deficiency in malabsorption.

PMID- 9290090
TI  - Effect of a glutamine-enriched diet on small bowel allograft during
      immunosuppressive therapy.
AB  - The effect of an orally administered glutamine-enriched elemental diet was
      examined following orthotopic small bowel allotransplantation using Brown Norway
      rats as donors and Lewis rats as recipients. The recipients was treated with FK
      506 and randomized to receive glutamine-free elemental enteral diet solution
      (glutamine-free group), glutamine-enriched elemental diet solution containing
      7500 mg of glutamine per 100 g diet (glutamine-enriched group) or standard chow
      (chow group) ad libitum for 7 d. There were no histological changes due to
      resection. Weight loss in the glutamine-enriched group was significantly less
      than that of the chow group. Both plasma glutamine levels and the ratio of
      glutamine to total amino acids in the homogenate of the graft mucosa of the
      glutamine-enriched group were significantly higher than those of the glutamine
      fee group. Villous height and crypt depth were significantly decreased in the
      glutamine-free group. The BrdU labeling index in the graft epithelium and
      alkaline phosphatase activity in the homogenate of the graft mucosa of the
      glutamine-enriched group were significantly higher than those of the glutamine
      free group. Therefore, orally administered glutamine-enriched elemental diet
      appears to promote the regeneration and differentiation of the graft mucosa
      following small bowel allotransplantation.

PMID- 9290091
TI  - Effects of insulin-like growth factor-1 on endotoxin translocation in burned rats
      receiving total parenteral nutrition.
AB  - The purpose of this study was to investigate the effect of insulin-like growth
      factor-1 (IGF-1) on the translocation of endotoxin from the gut of burned rats.
      Twenty-eight male Sprague-Dawley rats (7-wk-old) were subjected to 20% full
      thickness scald burns and were divided into two groups. One group received 4
      mg.kg-1.d-1 of IGF-1 (IGF-1 group, n = 14), and the other received saline
      (control group, n = 13). All rats were fed exclusively by total parenteral
      nutrition (TPN). On the second postburn day, rats were killed. The amount of
      endotoxin in the liver and spleen were measured. RNA from the terminal ileum was
      extracted, and Northern blot analyses of alpha-tubulin, beta-actin, cell division
      cycle-2 (cdc2), and immunoglobulin-A (IgA) were performed. Nitrogen balance was
      improved (p < 0.001), and the wet weight of intestine and its mucosa were
      increased significantly in the burned rats that received IGF-1. Gene expression
      of alpha-tubulin and beta-actin were not changed. Cdc2 was elevated (P < 0.05),
      but IgA was decreased (P < 0.05) in the IGF-1 group. Levels of endotoxin in the
      liver and spleen were significantly reduced (P<0.05) by the administration of IGF
      1. A negative correlation between the levels of endotoxin in the liver and the
      weight of the intestinal mucosa was observed. In conclusion, IGF-1 improved
      nitrogen balance, promoted the proliferation of intestinal mucosa and reduced the
      translocation of endotoxin.

PMID- 9290092
TI  - Nutritional efficacy of a spermidine supplemented diet.
AB  - Polyamines (PA) are ubiquitous cell components essential for growth. Dietary PAs
      are directed preferentially to tissues and organs that have been stimulated to
      grow by metabolic signals. Nutritional efficacy and growth potential of an oral
      PA supplement, spermidine (SD), was examined in growing rats. A group of 24-male
      Sprague-Dawley rats (200-220 g) was adapted to our vivarium conditions for 3 d,
      then fed ad libitum continuously for 14 d. During feeding they received either a
      basal diet (n = 8) or a test diet containing the basal diet with 0.05% SD (test
      diet 1, n = 8) or 0.10% SD (test diet 2, n = 8). This dose of SD corresponds to
      an intake of 54 and 108 mumol of SD per rat per day. At the end of 14 d of
      feeding, the animals were sacrificed and plasma, cerebral spinal fluid (CSF) and
      tissues (muscle, brain, and liver) were harvested for amino acid analysis.
      Voluntary food intake, body weight gain, and nitrogen excretion and balance were
      significantly decreased in test diet 2 fed rats compared to test diet 1. The
      opposing trends in the accumulation/depletion of free amino acids (AA) in muscle
      and plasma suggests that the exogenous supply of SD blocks the transport of amino
      acids, as well as PAs from the cells, since AA and PA share the same transport
      systems. A trend toward decreased weight gain and feeding efficiency was observed
      when high concentrations of SD were fed. It was concluded that feeding of SD at
      moderate intake is not toxic and does not retard growth. Oral administration of a
      smaller dose (<0.05%) of SD may promote further growth. The optimal level of SD
      dietary supplementation has thus yet to be established.

PMID- 9290093
TI  - Body fat distribution, insulin resistance, and metabolic diseases.
AB  - Obesity has now developed into a world-wide epidemic and is associated with large
      economic costs and prevalent diseases, particularly with central body fat
      distribution. Insulin resistance almost invariably occurs, and might be a major
      trigger for disease-generating mechanisms either directly or via generation of
      other disease precursors ("risk factors"). The hypothalamo-pituitary-adrenal
      (HPA) axis seems to be hypersensitive in abdominal obesity, a statement supported
      by increased responses to challenges from the adrenals to central regulatory
      centers. Furthermore, the feedback control by central glucocorticoid receptors,
      probably a secondary, functional consequence of an elevated HPA axis activity,
      because the receptor gene appears normal. Secretion of sex steroid and growth
      hormones is diminished, which might be consequence of elevated HPA axis activity.
      Hyperandrogenicity in women is probably of adrenal origin and another consequence
      of the sensitivity of the HPA axis. The endocrine abnormalities thus are
      periodically elevated cortisol and androgen (women) concentrations, as well as
      low secretions of gender-specific steroid and growth hormones. Since elevated
      cortisol, and low sex-steroid and growth hormone secretions, probably direct
      storage fat to visceral depots, the multiple endocrine abnormalities probably
      cause enlargement of these depots. Furthermore, these hormonal abnormalities most
      likely at least contribute to the creation of insulin resistance with additional
      effects of elevated fatty acids from central fat depots, which are sensitive to
      lipid mobilization agents. This chain of events indicates the central role of the
      hypersensitive HPA axis. Known causes of sensitization of this axis have been
      identified in subjects with abdominal obesity, including depression, anxiety,
      alcohol, and smoking. A common cause of HPA axis activation is perceived stress,
      with a depressive, defeatist, or "helplessness" reaction. In subjects with
      abdominal preponderance of body fat stores a number of psychosocial and
      socioeconomics handicaps have been identified, hypothetically predisposing to
      such reactions. In a primate model (monkeys), mild psychosocial stress is
      followed by identical psychological, endocrine, anthropometric, and metabolic
      abnormalities as in humans with abdominal preponderance of body fat stores,
      including early signs of diabetes and cardiovascular disease. These findings
      strongly support the interpretation that a stress reaction activating the HPA
      axis is involved also in the human syndrome. Interventions with normalization of
      the endocrine perturbations are followed by clear improvements of the multiple
      abnormalities in both clinical, experimental, cellular and molecular studies,
      suggesting that the pathogenesis of abdominal preponderance of body fat and its
      endocrine, anthropometric and metabolic abnormalities are indeed consequences of
      the endocrine abnormalities identified.

PMID- 9290094
TI  - Vitamin A homeostasis and diabetes mellitus.
AB  - Recent studies have shown that plasma concentrations of vitamin A (retinol) and
      its carrier proteins, retinol-binding protein (RBP), and transthyretin (TTR), are
      decreased in human subjects with insulin-dependent (IDDM) but not with noninsulin
      dependent diabetes mellitus (NIDDM). Rats made diabetic with streptozotocin (STZ)
      have also been shown to have reduced levels of plasma vitamin A while its hepatic
      concentrations elevate. The circulatory vitamin A levels remained low while its
      hepatic concentrations were further elevated following supplementation of the
      vitamin. The reduced circulatory status of vitamin A in diabetic animals was not
      caused by its impaired intestinal absorption. Further experimental studies have
      pointed to the fact that IDDM is associated with a deficiency of vitamin A, which
      is secondary to an impaired transport mechanism of this vitamin from its hepatic
      storage to the target site, such as retina of the eyes. The diabetes-associated
      changes in vitamin A metabolism were reserved to normal by insulin treatment. The
      underlying cause for decreased metabolic availability in uncontrolled diabetes,
      is not clearly understood. It appears that the increased hepatic store of vitamin
      A is attributed to a decreased availability of its carrier proteins. Subnormal
      vitamin A status in poorly controlled diabetic subjects may not respond to
      vitamin A supplementation, rather it may increase its load in the liver leading
      to hepatoxicity. These results clearly suggest that there is need for further
      research identifying the importance of vitamin A in diabetes mellitus.

PMID- 9290095
TI  - Maternal nutrition, fetal nutrition, and disease in later life.
AB  - Recent findings suggest that many human fetuses have to adapt to a limited supply
      of nutrients and in doing so they permanently change their physiology and
      metabolism. These "programmed" changes may be the origins of a number of diseases
      in later life, including coronary heart disease and the related disorders stroke,
      diabetes, and hypertension.

PMID- 9290096
TI  - Vitamin D deficiency in patients with intestinal malabsorption.

PMID- 9290097
TI  - Growth hormone therapy in intensive care patients: from biochemistry to muscle
      function.

PMID- 9290098
TI  - High proteins early in life as a predisposition for later obesity and further
      health risks.

PMID- 9290099
TI  - Early postoperative feeding.

PMID- 9290100
TI  - Weight gain, weight loss, and weight control: what is the role of physical
      activity?

PMID- 9290101
TI  - Relationship between omega-3 and omega-6 fatty acid ratios and breast cancer.

PMID- 9290102
TI  - Micronutrients and outcome.
AB  - Micronutrient deficiency not only causes symptoms of severe deficiency, but may
      also cause more subtle effects on tissue function, including immune deficiency
      and oxidative damage. The duration of a deficiency state, which is necessary
      before such effects are clinically significant, is not known. Most biochemical
      tests are relatively insensitive in detecting changes in micronutrient status,
      although they do provide a crude index. Many tests are nonspecific, being
      affected by the acute phase response as well as by nutritional status. Cellular
      tests are more sensitive and specific than tests in plasma. When interpreted
      carefully in association with the knowledge of the patient's clinical condition
      and nutritional intake, laboratory tests can be helpful in diagnosing deficiency
      states or conditions of excess provision, and in monitoring progress. Well
      conducted clinical trials of micronutrients in nutritional support are beginning
      to appear in the literature. Further studies are urgently required that relate
      outcome to levels of provision and biochemical indices of nutrient status.

PMID- 9290103
TI  - Vitamin C: what do we know and how much do we need?

PMID- 9290104
TI  - Supplementation of diets with nutritional pharmaceuticals.

PMID- 9290105
TI  - The competencies continuum in nutrition.

PMID- 9290106
TI  - From the binomial to the Poisson distribution.

PMID- 9290107
TI  - Eduard Schwarz, a neglected pioneer in the history of nutrition.
AB  - An account of the journey around the world by the Austrian ship's doctor Eduard
      Schwarz on a sailing ship from 1857 to 1859, his successful cure of
      nightblindness among the sailors, and how he was maligned by some of the Viennese
      medical press for his view that nightblindness is a nutritional disorder.

PMID- 9290108
TI  - Nutritional support in the critically ill: introduction.

PMID- 9290109
TI  - Energy metabolism in sepsis and injury.
AB  - The development of malnutrition is often rapid in critically ill patients with
      sepsis and severe trauma. In such patients, a wide array of hormonal and
      nonhormonal mediators are released, inducing complex metabolic changes.
      Hypermetabolism, associated with protein and fat catabolism, negative nitrogen
      balance, hyperglycemia, and resistance to insulin, constitute the hallmark of
      this response. Critically ill patients demonstrate a marked alteration in the
      adaptation to prolonged starvation: resting metabolic rate and tissue catabolism
      stay elevated, while ketogenesis remains suppressed. The response to nutrition
      support is impaired. Substrate use is modified in septic and traumatized
      patients. Glucose administration during severe aggression does not suppress the
      enhanced hepatic glucose production and the lipolysis. This phenomenon, related
      to tissue insulin resistance, ensures a high flow of glucose to the predominantly
      glucose-consuming cells, such as the wound, the inflammatory, and immune cells,
      all insulin-independent cells. In addition, the elevated protein catabolism is
      difficult to abolish, even during aggressive nutrition support. Thus, in patients
      with prolonged aggression, these alterations produce a progressive loss of body
      cell mass and foster the development of malnutrition and it dire complications.
      In this review, the relevant physiologic data and the nutritional implications
      related to energy metabolism in septic and injured patients are discussed, while
      potential therapeutic strategies are proposed.

PMID- 9290110
TI  - Metabolic response to injury and sepsis: changes in protein metabolism.
AB  - The metabolic response to trauma and sepsis involves an increased loss of body
      proteins. Specific sites of changes of protein and amino acid metabolism have
      been identified. In skeletal muscle, the rate of proteolysis is accelerated
      greatly. The rate of protein synthesis also may be increased but not enough to
      match the increase in degradation. Intramuscular glutamine concentration is
      decreased because of increased efflux and possibly decreased de novo synthesis.
      In the liver, the rate of synthesis of selected proteins (i.e., albumin,
      transferrin, prealbumin, retinol-binding protein, and fibronectin) is decreased,
      whereas acute phase protein synthesis is accelerated. Tissues characterized by
      rapidly replicating cells, such as enterocytes, immune cells, granulation tissue,
      and keratinocytes, exhibit early alterations in the case of decreased protein
      synthesis capacity. In these tissues, glutamine use is accelerated. Increased
      stress hormone (cortisol and glucagon) and cytokine secretion, as well as
      intracellular glutamine depletion, are potential mediators of altered protein
      metabolism in trauma and sepsis. However, the relative importance of these
      factors has not been clarified. Therapy of acute protein catabolism may include
      the use of biosynthetic human growth hormone, possibly in combination with
      insulin-like growth factor-1, and the administration of metabolites at
      pharmacologic doses. We recently studied the effects of carnitine and alanyl
      glutamine administration in severely traumatized patients. We found that both
      carnitine and the glutamine dipeptide restrained whole-body nitrogen loss without
      affecting selected indices of protein metabolism in the skeletal muscle.

PMID- 9290111
TI  - The route of nutritional support in the critically ill: physiological and
      economical considerations.
AB  - Although it generally is accepted that early enteral nutrition is of benefit to
      critically ill patients, there is little evidence to support this assertion.
      Nevertheless, enteral nutrition has many advantages over total parenteral
      nutrition (TPN), the latter being associated with several complications. Animal
      studies have shown that injury and infection can lead to gut atrophy and
      increased mucosal permeability. Translocation of bacteria and endotoxin in these
      animal models may initiate a systemic inflammatory response and cause multiple
      organ failure (MOF). Again, there is little direct evidence to suggest that
      similar mechanisms operate in humans. As a cause of MOF, simple splanchnic
      ischemia and reperfusion may be sufficient with no absolute requirement for
      translocation. In this setting, enteral nutrition may preserve splanchnic blood
      flow and prevent mucosal breakdown. Unfortunately there is a widespread
      misconception that gastric stasis, the absence of bowel sounds, and recent
      abdominal surgery preclude enteral feeding. There are few absolute
      contraindications to early enteral feeding and with motivated staff, the use of
      prokinetics, and the availability of jejunal feeding tubes, the majority of
      intensive care patients can be fed enterally. Enteral feeding is more cost
      effective than TPN, but TPN remains a common therapeutic intervention in the
      intensive care unit and represents a significant burden on health care budgets.
      Nutrition support teams have led to savings, particularly by identifying patients
      who have been inappropriately prescribed TPN and also by preventing excessive
      enteral feeding.

PMID- 9290112
TI  - Adjunctive therapies in nutritional support.
AB  - The need for new therapeutic approaches to improve the metabolic and clinical
      efficacy of nutritional therapy has been increasingly emphasized. The field of
      nutrition support of catabolic, malnourished, or hospitalized patients is rapidly
      evolving in response to the beneficial effects observed with adjunctive therapies
      in animal models and in emerging clinical investigations. Enteral nutrition is
      being increasingly administered, and enteral diets are being tested to improve
      gut structure and function. Adjunctive therapies in enteral and parenteral
      nutrition are being actively investigated. These include administration of
      recombinant growth factors and anabolic steroid hormones (e.g., growth hormone,
      oxandrolone); conditionally essential amino acids (e.g., arginine, glutamine);
      novel lipid products (e.g., structured lipids, fish oils); nutrient antioxidants
      (e.g., vitamins C and E); and combinations of these approaches. It is likely that
      current methods of enteral and parenteral nutrition support will evolve in
      response to the results of these research studies.

PMID- 9290113
TI  - Recent developments in lipid emulsions: relevance to intensive care.
AB  - For years, intravenous lipid supply has been considered as a means of providing
      an efficient fuel to many tissues of the body and of preventing or correcting
      essential fatty acid deficiency. The potential for lipid emulsions to modulate
      cell function via their content of specific fatty acids and of liposoluble
      vitamins has not received much attention yet. Soybean [long-chain triglycerides
      (LCT)] emulsions provide a valuable source of energy, but they are excessively
      rich in omega-6 essential fatty acids (FAs). Their infusion is associated with an
      accumulation of linoleate and a reduction of long-chain (> or = C20) omega-6 and
      omega-3 fatty acids in cell membrane phospholipids, as well as with a depletion
      of antioxidant status, associated with a reduction of alpha-tocopherol in plasma
      lipoproteins. Infusions of the mixed medium-chain triglycerides (MCT)/LCT
      (50%:50%; wt:wt) largely bypass these disadvantages. In addition, plasma
      elimination of MCT/LCT is faster than that of LCT. Recent advances indicate a
      great potential for omega-3 FAs incorporated into membrane phospholipids to
      modulate cell response to various stimuli and to influence several intracellular
      metabolic processes. Furthermore, some of these FA directly influence the
      production and the action of important mediators, the eicosanoids. In practical
      terms, an increased intake of omega-3 FAs may reduce inflammatory and thrombotic
      responses while protecting tissue microperfusion and immune defenses. Such
      properties may find interesting applications in several types of intensive care
      unit patients, provided that omega-3 FA incorporation takes place promptly. We
      recently had the opportunity to study in vitro and in vivo the metabolism of
      emulsions made of a mixture of MCT, soybean LCT, and fish oil triglycerides.
      Plasma elimination of such preparations appeared to be very fast, and their
      infusion was not associated with a prolonged residence of emulsion particles. In
      addition, uptake of remnants enriched with omega-3 FAs and liposoluble vitamins
      was fairly fast and occurred in several types of cells, leading to an efficient
      incorporation of omega-3 FAs in cell membranes within a few hours. The
      understanding that remnant uptake plays a significant role in the delivery of
      components included in lipid emulsions opens new areas of investigation and is
      likely to find several conditions of applications for new types of preparations.

PMID- 9290114
TI  - Can body composition in multiple organ failure be favorably influenced by
      feeding?
AB  - Multiple organ failure is the final common path of numerous medical conditions
      whereby the various organ systems fail and are supported by pharmacologic or
      mechanical means. The patient appears septic but often no septic focus can be
      found. Whole body protein dynamics are similar to severe sepsis with an elevation
      of both synthesis and breakdown. Lean body mass is not maintained even in the
      presence of an apparently adequate energy intake. The more common methods of
      assessing body composition are all confounded by fluid retention, which also
      limits parenteral nutrient intake. There are also difficulties with the tolerance
      of enteral feeding. In the long term, pharmacologic methods are going to be
      required if it is deemed that the maintenance of body mass is desirable, but in
      the interim, a robust noninvasive method is required of monitoring body mass in
      the presence of severe edema.

PMID- 9290116
TI  - Plasma selenium levels and the risk of colorectal adenomas.
AB  - Previous research has suggested that selenium may protect against the development
      of colorectal neoplasia. We examined the potential chemopreventive properties of
      selenium against colorectal adenomas while controlling for a number of dietary
      and life-style factors. We conducted a cross-sectional study among patients
      referred for colonoscopy to University of North Carolina Hospitals. Cases had one
      or more pathologically confirmed adenomas, and noncases had none. Plasma selenium
      levels were determined using graphite furnace atomic absorption spectrometry with
      Zeeman background correction and platform technique. Odds ratios were calculated
      using logistic regression analysis adjusting for potential confounders. The mean
      plasma selenium concentrations for cases (n = 37) and noncases (n = 36) were 107
      and 120 micrograms/l, respectively (p = 0.06). Those in the fourth quartile of
      plasma selenium level had 0.24 times the risk (95% confidence interval = 0.06
      1.04) for colorectal adenomas of those in the first quartile. The adjusted odds
      ratio for colorectal adenomas was 0.58 (95% confidence interval = 0.31-1.08) for
      a 30 microgram/l increase in plasma selenium level. Lower plasma selenium levels
      were associated with multiple adenomas but not with adenoma size or location.
      These data support a protective effect of selenium against colorectal adenomas
      after adjustment for possible confounders. Selenium might be a potentially useful
      chemopreventive agent for colorectal neoplasia.

PMID- 9290115
TI  - Cell density and antioxidant vitamins determine the effects of hyperoxia on
      proliferation and death of MDCK epithelial cells.
AB  - Epithelial cells are prone to oxidant injury, which could change epithelial cell
      homeostasis and lead to degenerative diseases. We examined the effects of
      hyperoxia on death and proliferation off Madin-Darby canine kidney (MDCK)
      epithelial cells and antioxidant vitamin protection. Subconfluent and near
      confluent MDCK cells were cultured under normoxia or hyperoxia for two days. We
      measured cell number and viability, mitochondria enzymatic activity, thymidine
      incorporation, necrosis [lactate dehydrogenase (LDH) release], and apoptosis (DNA
      fragmentation and morphological changes). When the cells were subconfluent,
      hyperoxia decreased the number of adherent cells, mitochondrial enzymatic
      activity, and thymidine incorporation, but neither LDH release nor apoptotic
      changes increased compared with normoxic controls. In normoxia, near-confluent
      cells had lower nonadherent cell numbers, mitochondrial enzymatic activity, and
      thymidine incorporation than subconfluent cells; hyperoxia further decreased the
      latter two parameters and increased apoptotic changes and LDH release in near
      confluent cells. Vitamin E protected mitochondrial enzymatic activity, apoptotic
      changes, and LDH release against hyperoxic injury but did not affect changes in
      thymidine incorporation with hyperoxia. Vitamin C partially protected the
      mitochondrial enzymatic activity and thymidine incorporation in subconfluence,
      but not in near confluence. These results indicate that cell density is a major
      determinant of the effects of hyperoxic injury and the profile of antioxidant
      vitamin protection.

PMID- 9290117
TI  - Nonlipopolysaccharide component(s) of Lactobacillus acidophilus stimulate(s) the
      production of interleukin-1 alpha and tumor necrosis factor-alpha by murine
      macrophages.
AB  - Previous studies in our laboratory suggested that Lactobacillus acidophilus
      strain DDS-1 (LA1) has a suppressive effect on chemically induced tumors in
      experimental animals. In an effort to understand the possible mechanisms
      underlying this effect, we investigated the ability of LA1 to induce the
      production of interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha
      (TNF-alpha), which have potent cytocidal and cytostatic effects on tumor cells.
      The mouse macrophage cell line RAW264.7 was incubated with live or heat-killed
      cells of four strains of L. acidophilus or Bifidobacterium bifidum. Escherichia
      coli was used as a source of lipopolysaccharide that is known to induce the above
      cytokines. The amount of the cytokines present in the culture fluid was
      quantitated by an enzyme-linked immunosorbent assay. LA1 induced the production
      of higher levels of IL-1 alpha and TNF-alpha than other lactobacilli and
      bifidobacteria. Stimulation of the production of the cytokines was not due to the
      lipopolysaccharide (LPS) component, since LPS at concentrations equivalent to, or
      100-fold greater than, that of LA1 induced only negligible amounts of IL-1 alpha
      and TNF-alpha. These results reveal that non-LPS component(s) of LA1 stimulate(s)
      the production of IL-1 alpha and TNF-alpha by macrophages, indicating that this
      organism stimulates the production of immunologic factors.

PMID- 9290119
TI  - Immunomodulatory effect of beta-carotene on T lymphocyte subsets in patients with
      resected colonic polyps and cancer.
AB  - Results from a number of studies suggest that beta-carotene-containing foods
      prevent the initiation or progression of various cancers. One possible mechanism
      for this effect could be enhancement of the immune response. The aim of this
      study was to determine whether beta-carotene modulates T lymphocyte subsets in
      patients affected with colonic polyps or cancerous lesions. Patients with
      previous adenomatous colonic polyps (n = 18) or colon cancers (n = 19) were
      randomized to receive placebo or beta-carotene (30 mg/day) for three months.
      Percentages of T lymphocyte subsets were determined using flow cytometry in blood
      samples collected before randomization and at three months. T lymphocyte subsets
      of 14 normal control subjects were also determined for comparison. Initially,
      there was no difference in total leukocyte counts, percentage of lymphocytes, and
      various subsets of lymphocytes among the three groups, although in cancer
      patients there was a lower percentage of CD4 and interleukin-2 (IL-2) receptor
      positive (IL-2R+) cells than in patients with polyps and in controls. After
      supplementation with beta-carotene, a significant increase in IL-2R+ T
      lymphocytes (from 12.7 +/- 3.0% to 26.0 +/- 1.9%) and CD4+ lymphocytes (from 40.9
      +/- 3.1% to 45.6 +/- 3.2%) was seen only in the cancer patients. These
      percentages remained unchanged in patients with adenomatous polyps receiving
      placebo or beta-carotene. We concluded that beta-carotene increased the number of
      IL-2R+ T lymphocytes and CD4+ lymphocytes, which in turn may produce IL-2 only in
      patients with cancer who may already have some deficiency in their immune system.
      This increase in activated T lymphocytes may mediate cytotoxic reactions to
      cancer cells via cytokine production.

PMID- 9290118
TI  - Expression of c-myc in human colonic tissue in response to beta-carotene
      supplementation.
AB  - Dietary supplementation with beta-carotene at 30 mg/day results in an increased
      serum trans-retinoic acid concentration in patients with a prior colonic polyp.
      In a number of human cell lines, trans-retinoic acid upregulates c-myc mRNA
      expression in colonic mucosa by reverse transcription polymerase chain reaction
      and correlated the results with serum concentrations of all-trans- (ATRA), 13-cis
      (13-cRA), and total retinoic acid. Serum and colonic biopsy samples were obtained
      before and 90 days after administration of a placebo (n = 7) or 30 mg of beta
      carotene (n = 5) daily. An increase in c-myc expression after supplementation was
      observed in 6 of 12 subjects, but 5 of these 6 subjects had decreased total serum
      retinoic acid concentration and 4 had decreased ATRA concentration. In addition,
      five of the six subjects with increased c-myc expression had received a placebo.
      Conversely, c-myc expression was increased in only two of five paired samples
      from subjects whose total serum retinoic acid concentration increased during the
      90-day supplementation period. We conclude that c-myc expression is not
      correlated with ATRA, 13-cRA, or total retinoic acid concentration in vivo and
      that increased serum retinoic acid secondary to increased tissue beta-carotene is
      not sufficient to activate c-myc transcription.

PMID- 9290120
TI  - Modification of azoxymethane intestinal carcinogenesis in rats by feeding sucrose
      boluses, pasta, and glucose.
AB  - We studied whether repeated boluses of sucrose or diets containing carbohydrates
      with a variable glycemic index (GI) affect intestinal carcinogenesis in rats.
      Male F344 rats were treated twice (1 wk apart) with 15 mg/kg sc azoxymethane
      (AOM) and then divided into four experimental dietary groups with different
      carbohydrate composition and administration schedules: the sucrose group was fed
      44% (wt/wt) sucrose (GI = 65), the bolus group was fed sucrose as carbohydrate
      and 43 boluses of sucrose (10-15 g/kg) at various time intervals, the pasta group
      was fed pasta [77% (wt/wt) cooked pasta, GI = 55], and the glucose group was fed
      44% (wt/wt) glucose (GI = 97). All nutrients, including carbohydrates, were
      provided in similar amount to the different groups. The experiment was terminated
      between Day 230 and Day 245 after AOM administration. At this time the pasta
      group had significantly higher cecal short-chain fatty acids than the other
      groups. Intestinal adenomas and cancers occurred with the same frequency in the
      bolus, sucrose, and glucose groups. On the contrary, we observed a significant
      decrease (p = 0.03) in the cumulative incidence of intestinal adenomas, but not
      adenocarcinomas, in the pasta group compared with the sucrose group (intestinal
      adenoma incidence in the pasta group was 31% compared with 63% in the sucrose
      group, 46% in the bolus group, and 37% in the glucose group). In conclusion,
      these results do not support the hypothesis that sucrose boluses or carbohydrates
      with a high GI stimulate colon carcinogenesis, but they indicate that foods such
      as pasta may exert a protective effect.

PMID- 9290121
TI  - S-allylmercaptocysteine, a stable thioallyl compound, induces apoptosis in
      erythroleukemia cell lines.
AB  - The antiproliferative potential of S-allylmercaptocysteine (SAMC), a stable
      organosulfur compound of aged garlic extract, has been investigated using two
      erythroleukemia cell lines, HEL and OCIM-1. It induces a dose-dependent
      inhibition of cell growth with a 50% lethal dose of 0.046 mM for OCIM-1 cells and
      0.093 mM for HEL cells. [3H]thymidine incorporation was reduced in cells treated
      with this thioallyl compound, and analysis of high-molecular-weight DNA showed
      fragmentation compatible with apoptosis. Flow cytometric analyses of DNA revealed
      an abnormal cell cycle progression in both types of erythroleukemia cells, with
      the major portion of the unsynchronized cells in the G2/M phase. Measurement of
      acid-soluble free sulfhydryl groups showed an initial increase in response to
      SAMC followed by a progressive dose-dependent decrease with extended incubation
      of cells. We conclude from these studies that SAMC is an effective
      antiproliferative agent against erythroleukemia cells that induces cell death by
      apoptosis.

PMID- 9290123
TI  - Effect of dietary supplementation of selenite on pulmonary metastasis of melanoma
      cells in mice.
AB  - The purpose of the present study was to determine the effect of dietary
      supplementation of selenite on experimental pulmonary metastasis of B16BL6 murine
      melanoma cells in C57BL/6 mice by means of an intravenous injection model. Three
      groups of mice were fed a basal AIN-93G diet containing 0.1 ppm selenium (control
      group) or the basal diet supplemented with 2 or 4 ppm selenium as selenite
      (experimental groups). Mice were fed the diet for two weeks before and after the
      intravenous injection of 0.75 x 10(5) viable tumor cells. At necropsy the number
      of tumors that developed in the lungs and their cross-sectional area were
      determined, and tumor volume was calculated. In the control group, 12 of the 15
      mice had > or = 1 lung tumors. In contrast, only 4 of the 15 mice in each of the
      selenite-supplemented groups had > or = 11 tumors. The incidence of metastasis in
      mice fed the control and the 2- and 4-ppm selenium diets was 93%, 73%, and 53%,
      respectively. The median number of lung tumors was 53, 1, and 1 in mice fed the
      basal and the 2- and 4-ppm selenium diets, respectively. Tumor cross-sectional
      area and tumor volume were significantly decreased in selenite-supplemented
      groups. These results demonstrate that dietary supplementation of selenite
      reduced pulmonary metastasis of B16BL6 melanoma cells in C57BL/6 mice and also
      inhibited the growth of the metastatic tumors that developed in the lungs. It is
      concluded that selenite may be a useful adjuvant to prevent metastatic diseases
      in cancer patients.

PMID- 9290122
TI  - NADPH-cytochrome P-450 reductase, cytochrome P-450 2C11 and P-450 1A1, and the
      aryl hydrocarbon receptor in livers of rats fed methyl-folate-deficient diets.
AB  - We investigated three hepatic cytochrome P-450 isozymes and the aryl hydrocarbon
      (Ah) receptor in rats fed one of the following three diets for 15 months: a diet
      containing the AIN vitamin mixture (control), the control diet devoid of choline
      and folate (CFD), or the CFD diet devoid of niacin (CFND). Hepatic tumors
      developed in all CFD- and CFND-fed rats. Western blot analyses of nontumor
      hepatic tissue showed that NADPH-cytochrome P-450 reductase (P-450 reductase)
      increased significantly in the CFD and CFND groups compared with the control
      group. Hepatic cytochrome P-450 2C11 (CYP2C11) was not detectable in the CFD and
      CFND groups compared with the control group. Ah receptor and cytochrome P-450 1A1
      (CYP1A1) were detected in higher amounts in livers of both deficient groups.
      CYP1A1 is an enzyme associated with bioactivation of exogenous genotoxins. To our
      knowledge, this is the first time it has been shown that CYP1A1 and the Ah
      receptor are induced by dietary deficiencies.

PMID- 9290124
TI  - The nonfermentable dietary fiber lignin alters putative colon cancer risk factors
      but does not protect against DMH-induced colon cancer in rats.
AB  - The effect of supplementation of the diet with autohydrolyzed lignin on 1,2
      dimethylhydrazine (DMH)-induced colon carcinogenesis was studied using 112 male
      Sprague-Dawley rats. Rats received eight weekly injections of DMH (9.5 mg/kg
      s.c.) or the saline vehicle solution and then were maintained on a basal AIN-76
      fiber-free diet or the basal fiber-free diet plus 5% or 10% (wt/wt) lignin for 24
      weeks. Rats were killed 32 weeks after the start of the experiment. Colon tumor
      incidence, location, and multiplicity were determined. Body weight, caloric
      intake, fecal dry weight, gut transit time, pH of cecal contents, and total fecal
      bile acid excretion were measured. Supplementation of the diet with 5% or 10%
      lignin resulted in increased fecal dry weight and total fecal bile acid excretion
      and in decreased gut transit time, colon pH, and fecal bile acid concentration.
      Dietary lignin did not significantly affect colon tumor incidence or multiplicity
      compared with the fiber-free diet. Thus dietary supplementation with
      autohydrolyzed lignin, a food fiber with good bulking characteristics, had a
      significant effect on several factors that have previously been linked to
      reduction of colon cancer risk, but the consumption of high levels of lignin did
      not decrease the risk for colon cancer.

PMID- 9290125
TI  - Inhibitory effects of phytopolyphenols on TPA-induced transformation, PKC
      activation, and c-jun expression in mouse fibroblast cells.
AB  - The effects of 12 phytopolyphenols, including 3 catechin derivatives, 8
      flavanols, and curcumin, on 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced
      transformation in mouse fibroblast cells are described. The location of hydroxyl
      functional groups at 2', 3', or 4' site(s), especially at the 4' site, as in
      apigenin, fisetin, morin, myricetin, and quercetin, seems essential for anti-TPA
      induced transformation, anti-protein kinase C (PKC) activation, and anti-TPA
      induced c-jun expression activities. Among the catechin derivatives, those with a
      cis form structure and with an additional hydroxyl group at the R1 site and
      galloyl groups at the R2 site, such as epigallocatechin gallate, have stronger
      inhibitory effects on the above-mentioned biochemical activities. Considering
      their polarities and chemical structures, these compounds have different oxygen
      radical absorbance capacity in the in vitro assay. In addition, curcumin also has
      these inhibitory effects on the above-mentioned biochemical activities and
      antioxidant activities for peroxyl radical but not hydroxyl radical. In addition
      to PKC activation, active oxygen species production, and c-jun induction, our
      data suggest that TPA treatment induces cellular transformation by other unknown
      routes, because some tested compounds have an inhibitory effect on TPA-induced
      transformation but have no or a slight inhibitory effect on PKC activation,
      active oxygen species production, and c-jun induction.

PMID- 9290126
TI  - Modulation of phase I and phase II xenobiotic-metabolizing enzymes by selenium
      enriched garlic in rats.
AB  - Previous research showed that treatment with selenium-enriched garlic (Se-garlic)
      was able to inhibit the initiation phase of mammary carcinogenesis in the
      dimethyl-benz[a]anthracene (DMBA) model in rats. The present study was designed
      to investigate the following parameters: 1) DMBA-DNA adduct formation in liver
      and mammary gland, 2) urinary excretion of DMBA metabolites, 3) phase I and phase
      II xenobiotic-metabolizing enzymes, and 4) tissue selenium levels as a function
      of Se-garlic supplementation. Prior feeding with an Se-garlic-containing diet (at
      3 ppm Se) for two weeks resulted in a consistent reduction of all DMBA adducts in
      liver and mammary gland. This was accompanied by a 40% increase in urinary
      excretion of DMBA metabolites over a two-day period. Several liver P-450 enzymes
      were examined in rats fed a diet supplemented with 1, 2, or 3 ppm Se. Compared
      with controls receiving 0.1 ppm Se, no significant alteration in activity was
      detected with respect to P-450 1A1 (responsible for DMBA activation), 1A2, 2B1,
      2E1, and 3A4. In contrast, glutathione S-transferase and uridine 5'-diphosphate
      glucuronyltransferase activities were elevated to a maximum of 2- to 2.5-fold in
      liver and kidney. As expected, there was a dose-dependent elevation of selenium
      concentrations in liver, kidney, mammary gland, and plasma as a function of the
      level of Se-garlic supplementation. Our data seem to suggest that an increased
      detoxification of carcinogen via the phase II conjugating enzymes might represent
      a mechanism of tumor suppression by Se-garlic.

PMID- 9290128
TI  - Antitumor effect of an oral administration of canthaxanthin on BALB/c mice
      bearing thymoma cells.
AB  - The antitumor effect of canthaxanthin in BALB/c mice bearing a transplantable
      thymoma was investigated. Male or female mice received two different doses of
      canthaxanthin (7 or 14 micrograms/g body wt/day) starting 15 days before tumor
      inoculation (7 x 10(7) cells i.p.). Canthaxanthin treatment delayed the
      appearance of macroscopic ascites and prolonged animal survival. This effect was
      dose dependent and more evident in females than in males. It appeared only when
      the carotenoid was administered before tumor transplantation. The antitumor
      efficacy of the carotenoid was related to its tissue incorporation. Canthaxanthin
      was incorporated in a dose-dependent manner in liver and thymoma cells and to a
      larger extent in females than in males. Our study shows the antitumor efficacy of
      canthaxanthin in vivo against a transplantable murine thymoma and points out the
      importance of dose, administration timing, and sex in the antitumor efficacy of
      this compound.

PMID- 9290127
TI  - Chronic dietary restriction influences tumor metastasis in the rat: parametric
      considerations.
AB  - Chronic dietary restriction is a well-documented means of inhibiting tumor
      growth. This study examines the effects of chronic dietary restriction on tumor
      metastasis in the rat. We investigate the effect of 1) the degree of food
      restriction, 2) the effect of preexposure to food restriction, and 3) the
      duration of food restriction after tumor inoculation on tumor metastasis. We also
      compare two methods of dietary restriction: 1) the time that food is available
      and 2) the amount of food available. Our findings demonstrate that rats
      restricted to 50% of ad libitum diet for one week before inoculation with MADB106
      tumor cells and for three weeks after inoculation exhibit a significant (p <
      0.001) reduction in lung colonization compared with animals fed ad libitum.
      Animals restricted to access to food for 4 hrs/day (60% of ad libitum) for the
      same period of time exhibit significantly (p < 0.005) greater lung tumor
      colonization than animals fed ad libitum. Preadaptation to the feeding regimen
      for one week before tumor inoculation proved to be critical in inhibiting tumor
      metastasis. The tumor-inhibitory effect was not significantly influenced by the
      duration of restriction after inoculation or by the manner in which food
      restriction was implemented. Finally, we demonstrate that inhibition of tumor
      colonization may be mediated by enhanced natural killer cell activity in the
      early postinoculation period.

PMID- 9290130
TI  - Oral administration of short-chain fatty acids reduces the intestinal mucositis
      caused by treatment with Ara-C in mice fed commercial or elemental diets.
AB  - Swiss mice fed commercial or elemental diets and an oral short-chain fatty acid
      (SCFA) solution or saline were treated with the cytostatic drug Ara-C
      (cytarabine, 3.6 mg/mouse/day) for two or four days. Histopathological
      examination revealed less damage (atrophy, inflammation, or necrosis) to the
      small intestine and colon caused by Ara-C when SCFA was administered.
      Accordingly, protein and nucleotide concentrations in the intestinal mucosa were
      higher in the group receiving SCFA than in the group receiving a placebo of the
      same pH and osmolarity. Improvement by SCFA treatment was correlated with an
      increase in the height of the intestinal villi, with no alterations of the
      crypts. Furthermore, the number of intraepithelial lymphocytes was similar to
      normal values in animals receiving SCFA and Ara-C. When large doses of SCFA were
      administered, xanthomized enterocytes appeared, suggesting an accumulation of
      fatty acids in these cells. We conclude that oral administration of SCFA at close
      to physiological proportions reduces the inflammation and necrosis caused by Ara
      C administration, thus representing a potential factor for the improvement of
      patients with mucositis caused by cancer treatment.

PMID- 9290129
TI  - Vitamin B6 suppresses growth and expression of albumin gene in a human hepatoma
      cell line HepG2.
AB  - The effect of vitamin B6 on the growth of a human hepatoma cell line HepG2 in
      culture was studied. The growth of HepG2 cells and protein synthesis were almost
      completely inhibited in medium supplemented with 5 mM pyridoxine. Pyridoxal was
      as effective as pyridoxine, but pyridoxamine showed no inhibitory action. The
      growth inhibition of HepG2 cells by pyridoxine was accompanied by a marked
      inhibition of secretion of plasma proteins, particularly albumin. Northern blot
      analysis of albumin mRNA showed that pyridoxine caused a rapid decrease in the
      expression of albumin gene. The electron-microscopic examination of pyridoxine
      treated HepG2 cells revealed a smoothing of nuclear membrane, a decrease in the
      number of nucleoli, and an appearance of aggregated heterochromatin structures.
      These morphological features are compatible with the depressed transcriptional
      activity in the pyridoxine-treated cells. The mechanism by which vitamin B6
      exerts its inhibitory effect was discussed in terms of our recent finding that
      vitamin B6 modulates expression of albumin gene by inactivating tissue-specific
      DNA-binding proteins. Binding of pyridoxal phosphate with tissue-specific
      transcription factors may reduce the capacity of these factors to interact with
      the regulatory region of albumin gene, resulting in the inhibition of the gene
      expression.

PMID- 9290131
TI  - Prenatal theophylline and necrotizing enterocolitis in premature newborn infants.
AB  - To determine whether prenatal theophylline therapy would increase the incidence
      of neonatal necrotizing enterocolitis (NEC) we studied bowel dysfunction in 59
      consecutive premature infants (g.s. < 34 weeks), whose mothers were treated with
      theophylline as a tocolytic during the last trimester, or as surfactant synthesis
      inductor, for at least three days prior to premature labor (Group A). As case
      control we considered the premature, matched for gestational age born immediately
      before, and whose was untreated with theophylline (Group B). NEC occurred in one
      patient from group A during the second postnatal week, and surgery was performed.
      First passage of meconium and start of enteral feeding were comparable in groups
      A and B, while gastric residuals lasting more than 4 days were found
      statistically increased (p < 0.03) in antenatally treated group A prematures.
      Furthermore, 18 out of 49 prematures postnatally treated with theophylline had
      gastric residuals (36%) with respect to 5 out of 69 untreated (7%) (p < 0.001).
      Also the premature infants treated ante and postnatally with theophylline showed
      a statistically significant increase of lasting gastric residuals with respect to
      the untreated, 13/16 vs 5/7, respectively (p < 0.03). Antenatal theophylline
      administered to high risk mothers, when maternal diseases do not allow the use of
      steroids, does not appear to later increase the risk of NEC in premature infants,
      and provides a chance to avoid the risks related to premature birth. Inhibitory
      activity on gut motility and gastric irritability are only detectable during the
      first postnatal days, enhanced by gut immaturity of preterm infants.

PMID- 9290132
TI  - [Syncopal pathology in childhood (II)].

PMID- 9290133
TI  - Normal variation in cutaneous blood content and red blood cell velocity in
      humans.
AB  - This study was designed to determine normal variations in cutaneous blood
      content, red blood cell content and skin thickness in healthy human volunteers.
      The blood content (BC) of human skin and the velocity of red blood cells (RBV)
      has been comprehensively mapped over 30 anatomical sites in 28 volunteers between
      the age of 7 and 77 years using reflectance spectrophotometry (RFS) and laser
      Doppler (LD) techniques respectively. Total skin thickness, which may have a
      relationship with blood content, has been mapped at the same anatomical sites in
      six of the volunteers using two-dimensional array, 12 MHz ultrasound equipment.
      The major determinant of BC and RBV was found to be anatomical site. Regardless
      of age, gender or prior sun exposure, anatomical sites above the waist produced
      higher readings than below. BC and RBV were found to be dependent on age and
      gender at most sites with higher readings being observed in males and younger
      volunteers. The largest difference was seen in males under 55 years whose RFS
      readings above the waist were significantly higher than in older males or females
      of any age. Heavy prior sun exposure and skin thickness could not be demonstrated
      to impact on either RFS or LD readings independently of the effects of anatomical
      site, gender or age. In general, RFS and LD readings paralleled one another and
      correlated linearly at most anatomical sites. While RFS readings tended to
      decrease in the cranio-caudal direction, LD readings were relatively uniform
      across the body except for the head and groin where they were higher, and the
      abdomen where they were lower. The site-to-site variations in RFS readings
      observed in this study correspond well to capillary density variations noted in
      previous studies.

PMID- 9290134
TI  - Correlation of radionuclide and optical tracer assessments of fluid flow in
      artificial ventricles.
AB  - Characterization of flow properties of an artificial ventricle may aid
      development of designs to minimize thrombosis. Techniques for determining two
      such flow properties, viz. ventricular clearance rate and ejection fraction, are
      compared and validated here for polyurethane and silicone rubber ventricles
      operated in a mock circulatory loop at various stroke volumes and pulse rates.
      Ventricular clearance rats were measured both by clinical radionuclide tracer
      techniques and by an optical tracer method. Ejection fractions were measured by
      radionuclide imaging and validated by direct measurements of flow rate and
      ventricular volume. Results from the two methods for ventricular clearance are in
      close agreement. The optical tracer method is superior in spatial resolution,
      convenience and economy, but the radionuclide tracer method for ejection fraction
      gives excellent agreement with the absolute measurements.

PMID- 9290135
TI  - Heart rate change as a function of age, tidal volume and body position when
      breathing using voluntary cardiorespiratory synchronization.
AB  - Voluntary cardiorespiratory synchronization (VCRS), where inspiration and
      expiration follows a fixed number of heart beats, was used to investigate heart
      rate change (HRC) in 16 subjects (grouped as 20-30 and 46-57 years of age) as a
      function of age, body position, and respiratory tidal volumes of 500 and 1000 ml.
      In phase I, the subjects, following a tone, inspired for two heart beats and
      expired for three beats. In phase II, the older group's breathing pattern was
      2/2, 2/3, 3/3, 4/4, 5/5, and 6/6 inspiratory and expiratory heart beats,
      respectively, per respiratory cycle. Comparing the younger and older groups, we
      found a statistically significant (p < 0.05) decrease in HRC for beat 1, 2, and 4
      of the respiratory cycle in the supine position, and also for beat 2 in the
      sitting position, but no significant change with tidal volume. The ratio of the
      younger to older group's beat 2 HRC was 2.54 sitting and 3.54 supine. Increasing
      the number of beats per respiratory cycle from four to 12 resulted in the HRC
      growing from 1.8 to 7.5 beats over the respiratory cycle, showing the importance
      of respiratory rate in measuring HRC. VCRS can easily observe the influence of
      each phase of the respiratory cycle on the HRC and show the unique phase
      dependent changes that occur.

PMID- 9290136
TI  - The study of steady magnetic fields associated with primary and secondary ST
      shift in ischaemic rabbit hearts.
AB  - The study of injury potentials associated with DC currents that generate the
      primary or secondary ST shifts during cardiac ischaemia is possible only through
      the invasive technique of the DC electrogram. Clinical surface ECG recordings are
      AC coupled and cannot be used. This paper reports the use of non-invasive and
      unshielded magnetocardiographic measurements to evaluate the DC injury currents
      associated with ST shifts during coronary artery occlusions in the isolated
      rabbit heart. The effect on the magnetic ST shift is studied under different
      ischaemic conditions including regional ischaemia, global ischaemia, global
      ischaemia following long periods of regional ischaemia, regional ischaemia after
      repeated episodes of reversible global ischaemia, and bilateral regional
      ischaemia. Recording of DC magnetic fields allows the characterization of primary
      and secondary ST displacement for each induced ischaemic condition. Our
      measurements show that the ST shift starts earlier when inducing ischaemia in
      hearts previously subjected to ischaemic episodes than in hearts where the
      ischaemia was produced for the first time.

PMID- 9290138
TI  - An assessment of infrared tympanic thermometers for body temperature measurement.
AB  - This article provides an experimental assessment of three commercially available
      clinical thermometers, using different thermal infrared sensors. This kind of
      thermometer measures body temperature by detecting infrared radiation from the
      tympanic membrane. These thermometers are growing in popularity thanks to their
      simplicity of use, rapid response and minimal distress to the patient. The
      purpose of the laboratory tests presented here was to assess the effect of
      varying ambient temperature and varying simulated patient temperature on the
      performance of the three infrared tympanic thermometers.

PMID- 9290137
TI  - Synchronous recording and review of oesophageal manometry and video fluoroscopy
      using a portable manometry recorder and PC with integrated digital video
      acquisition.
AB  - We present the technical details of a new system for the synchronous recording
      and review of a combined oesophageal manometry and video fluoroscopic barium
      swallow examination. The system developed uses a portable manometry recorder and
      personal computer (PC) with an integrated digital video acquisition system. These
      are controlled using software to enable the real time capture of digital video
      and manometric data throughout the combined examination. The recorded pressure
      waveforms can then be synchronously displayed on a screen with the recorded
      digital video of the fluoroscopic barium swallow. This new tool enables both
      comparative measurement and detailed analysis of the relationship between
      visualized bolus transport and pressure measurements. It provides for a deeper
      understanding and improved clinical assessment of complex motility disorders over
      those obtained when these two modalities are applied separately. The system is
      easily incorporated into a clinical radiology suite and it is both user and
      patient friendly. It uses readily available computer hardware together with
      multimedia software and is a comparatively economical addition to the radiology
      suite with the manometry analysis available fulfilling the criteria laid down by
      the Clinical Associates Group of the British Society of Gastroenterology.

PMID- 9290139
TI  - Hippocratic thermography.
AB  - The thermal measurement method of Hippocrates, which has been referred to as the
      first for measuring body temperature, was reproduced and the image obtained was
      compared with an infra-red radiation thermogram. Hippocrates' method involves
      covering the patient's thorax with an earth-soaked cloth. As the warmer areas dry
      faster, the pattern of enlargement of the dry area shows the temperature
      distribution. Therefore, it appears that Hippocrates was the first to obtain
      thermograms.

PMID- 9290140
TI  - A phantom for evaluating bone mineral density of the hand by dual-energy x-ray
      absorptiometry.
AB  - Dual-energy x-ray absorptiometry (DXA) is a precise, widely used method for
      measuring bone mineral density (BMD), usually of the lumbar spine and femoral
      neck. Recent developments, such as a lower x-ray tube current and pixel by pixel
      analysis, enable smaller bones and thinner tissues volumes, as in the hand, to be
      measured. Measurements of hand bone mineral content (BMC) and BMD could be useful
      in assessing disease severity in early rheumatoid arthritis and in monitoring
      disease progression and response to therapeutic intervention. A phantom is
      required for evaluating the software, measuring long-term precision and comparing
      with other DXA methods. This note describes the design and evaluation of a hand
      phantom for use on a Lunar DPX-L dual-energy x-ray absorptiometer. The phantom
      consists of three sections representing the metacarpals, and proximal and distal
      phalanges, using aluminum and Perspex as the bone and lean tissue equivalents
      respectively. The BMD of the three sections is approximately 1.0, 0.6 and 0.3 g
      cm-2. The phantom demonstrates limitations in the potential accuracy of BMD
      determination at low densities using the Small Animal Software on the Lunar DPX
      L. Improved recognition of low-density regions was obtained with the Lunar EXPERT
      with precision values of 0.9, 1.1 and 2.0% for the three sections of the phantom
      respectively.

PMID- 9290142
TI  - Immunohistochemical examination of trophoblast populations in human first
      trimester and term placentae and of first trimester spiral arteries with the
      monoclonal antibody GZ 112.
AB  - This paper presents an immunohistochemical study with a monoclonal mouse antibody
      GZ 112, an IgG1 kappa, which is directed against an antigen expressed in first
      trimester placenta by all proliferative and invasive extravillous trophoblast
      populations including a population of Langhans cells that represent extravillous
      stem cells. Additionally, the GZ 112 antigen is associated with morphological
      changes of spiral arteries preceding local trophoblast invasion. In term
      placentae, GZ 112 also strongly reacts with all extravillous trophoblast
      populations, but additionally recognizes partly villous cytotrophoblast and
      syncytiotrophoblast too, displaying a heterogeneous staining pattern. GZ 112 is
      directed against a 42-KDa antigen. Intracytoplasmic network-like staining and
      cross-reactivity with various human surface and glandular epithelia indicate a
      cytokeratin intermediate filament or a cytokeratin intermediate filament
      associated molecule as antigen.

PMID- 9290141
TI  - Cellular localization of gp46 at the human fetal-maternal interface.
AB  - gp46 is a collagen-binding heat-shock glycoprotein with a possible role in the
      biosynthesis of collagen as well as in cell differentiation and fusion. In this
      study, the relative levels of gp46 protein and its mRNA transcript were examined,
      as well as the mRNA levels of collagen types I and IV in first trimester and term
      human placental tissues. Western blot analysis revealed substantially higher
      levels of gp46 in first trimester placentae than in term placentae. Similarly,
      elevated levels of type IV collagen transcript were detected in first trimester
      relative to term issues. Interestingly, the levels of gp46 and type I collagen
      mRNA remained unchanged. Immunohistochemical analysis of first trimester tissues
      demonstrated intense gp46 staining in mononucleated villous and extravillous
      cytotrophoblasts, decidual cells and in the villous connective tissue stroma.
      Syncytiotrophoblast in the same tissues also exhibited gp46 staining but at a
      reduced intensity. In chronic villi of term placentae, faint gp46 staining was
      only observed in the syncytiotrophoblast layer. However, as in the first
      trimester placentae, intense labelling was evident in the extravillous
      cytotrophoblasts and decidual cells of these tissues. These results suggest a
      developmental regulation of gp46 expression at the fetal-maternal interface
      during pregnancy and suggest a possible functional link between gp46 and collagen
      type IV. during gestation.

PMID- 9290144
TI  - Cellular localization and developmental regulation of 11 beta-hydroxysteroid
      dehydrogenase type 1 (11 beta-HSD1) gene expression in the ovine placenta.
AB  - This study was designed to examine the cellular localization and developmental
      regulation of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) type 1 gene
      expression in the ovine placenta. Placental tissues were collected at discrete
      times between days 59 and 143 of pregnancy (term = 145 days). Levels of 11 beta
      HSD1 mRNA were determined by Norther blot analysis. The level of both
      dehydrogenase and reductase activities of 11 beta-HSD1 was assessed by a
      radiometric conversion assay using cortisol and cortisone as physiological
      substrates. The cellular localization of 11 beta-HSD1 protein was determined by
      standard immunohistochemical technique using a polyclonal antibody specific for
      the ovine protein. High levels of 11 beta-HSD1 mRNA were detected in the placenta
      by day 59, and there was a trend towards a decrease between days 98-103 and 125
      128 (P = 0.06). The level of placental 11 beta-HSD1 mRNA remained unchanged
      thereafter. Levels of both 11 beta-HSD1 dehydrogenase and reductase activities
      followed a similar pattern except that in both cases there was a significant
      decrease between 98-103 and 125-128 (P < 0.05). Moreover, under the present assay
      conditions, the dehydrogenase activity was always predominant, suggesting that
      the net effect of placental 11 beta-HSD1 activity would lead to glucocorticoid
      inactivation. Thus, the decreased 11 beta-HSD1 activity in the placenta at days
      125-128 was consistent with, and may help to explain, the apparent increase in
      the placental transfer of cortisol from mother to fetus during that time.
      Throughout pregnancy, intense 11 beta-HSD1 immunoreactivity was detected in fetal
      trophoblastic cells, maternal stromal cells and blood vessels. In contrast,
      maternal syncytium was immunonegative before day 125, but became immunopositive
      thereafter. The observed predominant direction of 11 beta-HSD1 activity in vitro
      and its pattern of localization in the ovine placenta are consistent with the
      hypothesis that placental 11 beta-HSD protects the fetus from adverse effects of
      maternal glucocorticoids by inactivating glucocorticoids locally.

PMID- 9290143
TI  - Highly specific monoclonal antibody demonstrates that pregnancy-specific
      glycoprotein (PSG) is limited to syncytiotrophoblast in human early and term
      placenta.
AB  - Pregnancy specific glycoproteins (PSG) in humans constitute a family of 11
      closely related glycoproteins (PSG1-8, PSG11-13) of unknown function(s), which
      are produced in large amounts by the placenta. As a step toward understanding the
      biology of PSG, specific monoclonal antibodies (mAbs) against PSG were developed
      and used to investigate the ultrastructural localization of PSG in the early and
      term placenta and in first trimester decidua. One mAb, BAP-3, was found to react
      with all six individually expressed PSGs representing five alternatively spliced
      forms, but not with any of the seven expressed members of the carcinoembryonic
      antigen (CEA) subfamily. The BAP-3 epitope is located in the PSG B2 domain. Using
      the BAP-3 mAb, PSGs were found to be expressed exclusively by the
      syncytiotrophoblast of first trimester and term villi. The intensity of the
      staining was much higher in early than in term placenta. All three main cellular
      compartments involved in the biosynthesis pathway of secreted proteins, i.e.
      rough endoplasmic reticulum, the Golgi complex and secretory vesicles, were
      stained for PSG. A second PSG-reactive mAb, BAP-1, also stained the apical plasma
      membrane of some glandular epithelial cells in first trimester decidua in
      addition to syncytiotrophoblast. This staining was most likely due to cross
      reactivity with biliary glycoprotein (BGP).

PMID- 9290145
TI  - Comparative localization of endothelial and inducible nitric oxide synthase
      isoforms in haemochorial and epitheliochorial placentae.
AB  - The presence and immunolocalization of type II (inducible or macrophage) and type
      III (endothelial) nitric oxide synthase (NOS) isoforms were compared in the term
      placentae of humans, rhesus monkeys, baboons, guinea-pigs, rats and sheep using
      isoform specific antibodies. In the human placenta, intense immunohistochemical
      staining for type III NOS was seen in syncytiotrophoblast with weaker staining in
      vascular endothelial cells. Only vascular endothelial cells showed positive III
      NOS staining in rhesus monkey, baboon, guinea-pig, rat and sheep placentae. No
      positive type III NOS immunostaining was seen in trophoblast from any non-human
      placentae. Western blotting revealed a 135-kDa type III NOS species in placental
      homogenates, semi-purified by ADP-sepharose affinity chromatography, from all the
      species tested confirming antibody specificity. Type II NOS immunostaining was
      localized to certain villous stromal cells which also stained for CD14 (a
      monocyte/macrophage marker) in the placenta of humans, rhesus monkeys, baboons
      and sheep. No specific immunohistochemical staining for type II NOS or CD14 was
      noted in the two rodent species, guinea-pig and rat. On Western blots, a 130-kDa
      type II NOS species was identified in semi-purified placental homogenates of
      every species except guinea-pig, although weak bands were seen for rhesus monkey
      and baboon. The failure of the antibodies to show type II NOS in the rat placenta
      by immunohistochemistry may be due to a difference in antigen conformation from
      Western blots. As only human placental syncytiotrophoblast expresses type III
      NOS, the putative functions ascribed to this isoform in syncytiotrophoblast,
      i.e., to prevent platelet and leucocyte aggregation in the intervillous space and
      adhesion to the trophoblast surface or to mediate peptide hormone release from
      trophoblast, may be unique to humans. Alternatively, syncytiotrophoblast-derived
      NO may fulfill some other unknown function. The similar pattern of expression of
      type II NOS in those species with villous fetomaternal interdigitation and
      multivillous fetomaternal blood flow interrelations may represent a more
      universal role in surveillance and/or protection against maternal insults or
      pathogens by immunologic activation and subsequent synthesis of nitric oxide
      which exerts a cytostatic/cytotoxic response.

PMID- 9290146
TI  - Tumour necrosis factor-alpha induces cyclo-oxygenase-2 gene expression in first
      trimester trophoblasts: suppression by glucocorticoids and NSAIDs.
AB  - Tumour necrosis factor-alpha (TNF-alpha) is a pleiotropic cytokine which
      stimulates the synthesis and release of prostaglandins (PGs) in several in vitro
      and in vivo models of preterm labour. While TNF-alpha simulated PG production has
      been described in decidual, amnion and myometrial cells, to date no studies have
      focused on the role of TNF-alpha in the stimulation of arachidonic acid
      metabolism in placental trophoblast cells. Cyclo-oxygenase-2 (COX-2) is the rate
      limiting enzyme in PG biosynthesis and is expressed de novo during cellular
      activation by cytokines. To test whether TNF-alpha alters expression of COX-2,
      trophoblasts from first trimester chorionic vili were cultured as a continuous
      cell line and treated with TNF-alpha alone or with TNF-alpha and dexamethasone
      (Dex). Total RNA and protein were extracted from the trophoblasts and subjected
      to Northern and immunoblot analysis, respectively. Northern blots were hybridized
      with a 32P-labelled probe encoding the COX-2 cDNA and immunoblots were incubated
      with anti-COX-2 antibodies. There was a time- and dose-dependent increase in COX
      2 mRNA and protein expression in cells stimulated with TNF-alpha. The effect of
      TNF-alpha on COX-2 mRNA and protein expression was inhibited by dexamethasone
      (Dex). To examine the production of PGE2 and PGF(2 alpha), specific RIAs were
      performed on culture media from similarly stimulated cells. PG accumulation after
      TNF-alpha stimulation occurred in a time- and dose-dependent fashion with a
      similar inhibition of PG accumulation after Dex exposure. To be certain that TNF
      alpha stimulated PGE2 production was, indeed, a result of COX-2 induction, RIAs
      were carried out with the COX-2-selective inhibitor NS-398. Cells stimulated with
      the NS-398 after TNF-alpha exposure demonstrated suppression of TNF-alpha
      stimulated PGE2 formation. The results suggest that TNF-alpha elicits part of its
      pathophysiologic effects in preterm labour via alterations in COX-2 gene
      expression within the placental microenvironment.

PMID- 9290147
TI  - Characterization of a sodium-dependent vitamin transporter mediating the uptake
      of pantothenate, biotin and lipoate in human placental choriocarcinoma cells.
AB  - The characteristics of the uptake of the vitamin pantothenate into JAr human
      placental choriocarcinoma cells were investigated and these cells were found to
      accumulate the vitamin against a concentration gradient by a Na(+)-dependent
      process. Substitution of Na+ with over other monovalent cations abolished the
      uptake completely. The transport process showed no preference for any particular
      anion. Kinetic analysis indicated the presence of a single saturable transport
      system with a Michaelis-Menten constant of 2.1 +/- 0.2 microM and a maximal
      velocity of 341 +/- 12 pmol/mg of protein per 10 min. The dependence of the
      uptake rate of pantothenate on Na+ concentration exhibited sigmoidal kinetics,
      indicating interaction of more than one Na+ ion with the transporter. The Hill
      coefficient for this process was calculated to be 1.6. The Na+/pantothenate
      coupling ratio being greater than unity suggests that the transport process is
      electrogenic, resulting in net transfer of positive charge across the membrane.
      This was confirmed in plasma membrane vesicles prepared from JAr cells where the
      uptake of pantothenate was found to be significantly stimulated by valinomycin
      induced inside-negative K(+)-diffusion potential. Substrate specificity studies
      showed that, in addition to pantothenate, the transporter interacts with two
      other vitamins, namely biotin and lipoate. The characteristics of pantothenate
      uptake in the placental cell line BeWo was also investigated. These cells were
      also found to express a pantothenate transport system similar to that expressed
      in the JAr cells.

PMID- 9290148
TI  - Thyroid hormone efflux from placental tissue is not stimulated during cell volume
      regulation.
AB  - The effects of cell swelling induced by hyposmotic shock on efflux of hybrid
      hormones and selected amino acids from human placental tissue were examined.
      Decreasing the osmolarity of external medium from 290 to 140 mOsm/kg stimulated
      release of taurine, tryptophan and glutamine from placental tissue fragments. The
      efflux rate constant for taurine increased from 0.0069 +/- 0.0012/min to 0.0646
      +/- 0.0217/min (n = 6) (P < 0.001), for tryptophan from 0.016 +/- 0.0010/min to
      0.0295 +/- 0.0016/min (n = 6) (P < 0.001), and for glutamine from 0.0267 +/-
      0.0027/min to 0.0659 +/- 0.0043/min (n = 4) (P < 0.001). In contrast, hyposmotic
      challenge did not affect release of triiodothyronine, thyroxine and leucine.
      These results indicate that transport processes involved in the regulation of
      cellular volume are unlikely to facilitate efflux of thyroid hormones from
      placental tissue, and therefore are unlikely to mediate transfer of thyroid
      hormones across the placenta. In addition, it is unlikely that the transport
      system facilitating the release of amino acids from placental tissue during
      regulatory volume decrease is one of the known amino acid carriers.

PMID- 9290149
TI  - Characterization of glutamine synthetase transcript, protein, and enzyme activity
      in the human placenta.
AB  - This study characterizes the molecular mechanisms necessary for glutamine
      synthesis in the human placenta. RNA hybridization and protein immunoblotting
      were used to verify the presence of glutamine synthetase (GS) transcripts and
      protein, respectively. Additionally, the presence of GS was determined by
      immunohistochemistry. RNA hybridization demonstrated the presence of 1.8- and 2.8
      kB transcripts and protein immunoblotting yielded a single 49-kDa band,
      characteristics of GS transcripts and protein, respectively. The mean (+/- s.d.)
      specific activity of placental GS, expressed as mumol gamma-glutamyl hydroxamic
      acid/mg protein/h was 1.80 +/- 0.59, which is comparable to other organs which
      are net glutamine producers. Immunohistochemical analysis indicated the presence
      of GS within the cytotrophoblast and mesenchyme layers of placental villi, but
      not in the syncytiotrophoblast. Although these results suggest that the human
      placenta is capable of synthesizing glutamine, the fate of glutamine produced by
      this organ remains speculative.

PMID- 9290150
TI  - Uptake of microparticles by rat visceral yolk sac.
AB  - The visceral yolk sac (VYS) is responsible for a major part of the amino acid
      nutrition of the early post-implantation rat embryo and possibly also at the
      fetal stage of gestation. The mechanism involves endocytic uptake of proteins by
      the tissue's epithelial cells followed by intralysosomal digestion to amino
      acids. The amino acid so generated are used for protein synthesis in both the
      embryo and the VYS. Previous reports had indicated that the endocytic capacity of
      the VYS might be limited to exclude larger macromolecules. This study
      demonstrates that Percoll, which comprises 30-nm silica particles coated with
      polyvinylpyrrolidone (PVP), is as effectively captured by the 17.5-day rat VYS
      cultured in vitro as PVP itself. Uptake of 125I-labelled Percoll was progressive
      with time over 5 h and was inhibited by a low incubation temperature, 2,4
      dinitrophenol (50 micrograms/ml), EGTA (5 mM), colchicine (10 micrograms/ml) or
      cytochalasin B (10 micrograms/ml). After uptake of 125I-labelled Percoll, VYSs
      released only 20 per cent of their radioactivity when re-incubated in fresh
      medium for 3 h. These data, and electron micrographs showing Percoll in
      intracellular vacuoles, are all consistent with uptake by endocytosis. Percoll's
      rate of uptake by the VYS indicates that, like 125I-labelled PVP, it enters the
      cell chiefly by fluid-phase pinocytosis. It is concluded that endocytosis by the
      VYS will efficiently capture even the largest globular proteins, and that
      previous indications of a relatively low size exclusion reflected the loosely
      coiled configuration of the synthetic polymers used in the earlier studies.

PMID- 9290151
TI  - Uptake and processing of 59Fe-labelled and 125I-labelled rat transferrin by early
      organogenesis rat conceptuses in vitro.
AB  - The delivery of iron to the early organogenesis rat embryo has been studied,
      using 59Fe- and 125I-labelled rat transferrin. Rat conceptuses at 9.5 days
      postconception were cultured for 27 or 51 h in whole rat serum. Rat transferrin
      labelled with 59Fe was added for the final 0.1, 0.5, 6, 24 or 48 h of culture.
      Radioactivity accumulated progressively in both the embryo and the visceral yolk
      sac. Similar results were obtained when unconjugated 59Fe3+ was added to the rat
      serum used as culture medium. Both acid-soluble and acid-insoluble 59Fe were
      substantially present in the embryo and yolk sac after all exposure periods. When
      conceptuses were cultured in the presence of 125I-labelled rat transferrin, acid
      soluble radioactivity was progressively released into the culture medium, but
      accumulation into the embryo and visceral yolk sac was slight and did not change
      with duration of exposure to the labelled protein. Similar findings were obtained
      using 125I-labelled bovine serum albumin. In these experiments, there was a close
      correspondence between the amount of iron accumulated by the embryo and visceral
      yolk sac in the final 24 h of a 51-h culture and the amount of transferrin
      converted into acid-soluble products in the same period. Visceral yolk sacs from
      17.5-day pregnant rats were explanted and cultured in the presence of 59Fe
      labelled rat transferrin, 125I-labelled rat transferrin or 125I-labelled bovine
      serum albumin, for periods up to 3 h. Again uptake of 59Fe increased with time of
      incubation, and the 125I-labelled proteins were digested to acid-soluble products
      which were released into the culture medium. The results indicate that
      transferrin delivers iron for incorporation into both the embryo and the visceral
      yolk sac, and are consistent with a mechanism involving receptor-mediated
      endocytosis of iron-laden transferrin by the cells of the visceral yolk sac. The
      transferrin itself appears to be quantitatively degraded, following delivery of
      iron to the yolk sac cells, a result that differs from findings in other cell
      types, in which the protein is not degraded but returns to the plasma membrane to
      participate in further cycles of iron acquisition and delivery.

PMID- 9290152
TI  - Increased N-glycosylation and reduced transferrin-binding capacity of transferrin
      receptor isolated from placentae of diabetic women.
AB  - Infants of diabetic mothers are frequently born iron deficient because their
      fetal iron demand exceeds placental iron transport capacity. Although transferrin
      receptor (TfR) expression is increased, binding to diferric transferrin is
      decreased proportionately to the severity of maternal disease. It is hypothesized
      that TfR isolated from diabetic placentae has altered N-glycosylation since
      proper glycosylation of N-linked oligosaccharides is important for normal TfR
      binding kinetics to diferric transferrin. TfR was obtained from
      syncytiotrophoblastic membranes of six diabetic and six non-diabetic human
      placentae. Competitive binding to 125I-transferrin demonstrated a higher Kd in
      the diabetic TfR (P = 0.04), directly correlated to cord serum C-peptide
      concentration (r = 0.81, P < 0.001). The molecular weight of the monomeric form
      of TfR prior to treatment with glycopeptidase F (PNG-F) was greater in the
      diabetic group (P < 0.001) was directly related to the Kd (r = 0.77, P = 0.002).
      Treatment with PNG-F eliminated the molecular weight difference between the two
      groups. Increased glycosylation of the N-linked oligosaccharides of TfR isolated
      from diabetic placentae may alter the three-dimensional structure or charge of
      the receptor, thus reducing its binding affinity for transferrin.

PMID- 9290153
TI  - Image analysis of protein profiles from paired microvillous and basal
      syncytiotrophoblast plasma membranes from term human placenta and
      characterization of IgG binding to membrane vesicles.
AB  - Image analysis of SDS-PAGE profiles of highly purified, paired maternal-facing
      (microvillous; MVM) and fetal-facing (basal; BM) plasmalemma membrane vesicles
      from six term human placentae showed that, while individual MVM or BM profiles
      were extremely reproducible, the two membrane populations were substantially
      different--although all of the seven major bands of molecular mass, 98.4, 79.4,
      71.1, 45.1, 40.9, 39.5 and 34.5 kDa found in MVM were present, albeit in
      differing amounts, in BM. BM were characterized by the presence of five low
      molecular weight bands which were not present in MVM. Despite this consistency of
      the membrane preparations, binding of 125I-IgG or its fragments showed marked
      variability in both MVM and BM. At pH 7.4, both MVM and BM bound similar amounts
      of 125I-IgG with Kd values of 5.2 +/- 1.9 x 10(-6) M (s.e., n = 8) and 2.9 +/-
      0.4 x 10(-6) M respectively, (P > 0.05). There were 1.2-1.6 x 10(15) binding
      sites/mg protein. Affinity constants for Fc fragment binding to MVM and BM were
      similar to those for IgG, although the Bmax value for BM Fc binding was greatly
      reduced compared to that for IgG (P > 0.001). Fab binding to MVM and BM was also
      saturable but substantially lower than that of Fc, whereas binding of F(ab')2 was
      low and linear. Both MVM and BM bound marginally more IgG at pH 6.0 than at pH
      7.4. These data provide further evidence for receptor-mediated transcytosis of
      maternal IgG across the placenta and confirm that the placental IgG transporter
      differs from classical Fc gamma receptors.

PMID- 9290154
TI  - In vitro cultured human term cytotrophoblast: a model for normal primary
      epithelial cells demonstrating a spontaneous differentiation programme that
      requires EGF for extensive development of syncytium.
AB  - Normal human term cytotrophoblast cells prepared by trypsin-DNAse I digestion
      with and without secondary immunological purification with CD9 antibodies were
      investigated for the expression of morphological and genetic markers of
      proliferation and differentiation. After 24 h of culture, the cell preparations
      demonstrated spontaneous formation of microvilli and formation of small syncytial
      units as assessed by desmoplakin staining and FITC-dextran microinjection. EGF
      was required for mature syncytial formation. Compared to log-phase proliferating
      HeLa cells, uptake of [3H]thymidine incorporation was low and quickly decreased
      to negligible levels. Expression of the proto-oncogenes c-myc, c-fos, and c-jun
      and histone 2A decreased rapidly in the first 24 h of culture in both cell
      preparations, followed by an increase in expression of c-fos and junB over the
      next 3 days of culture. Proto-oncogene changes were similar in attached and
      suspension cells. Spontaneous increases in alpha hCG, pregnancy-specific beta(1)
      glycoprotein and 3 beta-hydroxysteroid dehydrogenase (3 beta OHSD) occurred
      within 1 day in both cell preparations. EGF receptor blocking antibodies did not
      inhibit minor degrees of spontaneous syncytial formation nor inhibit spontaneous
      expression of alpha hCG or 3 beta OHSD mRNA, but did prevent extensive
      synctialization induced by EGF. The results demonstrate that term cytotrophoblast
      cells even in serum-free conditions or suspension culture rapidly commit to a non
      proliferative differentiation program in culture which includes limited
      syncytialization and marked hormone mRNA expression. However, EGF is required for
      extensive syncytial development.

PMID- 9290155
TI  - Vascular effects of PTHrP (1-34) and PTH (1-34) in the human fetal-placental
      circulation.
AB  - The aim of this study was to examine the vasodilatory effects of parathyroid
      hormone-related protein (PTHrP) (1-34) and parathyroid hormone (PTH) (1-34) on
      the human fetal-placental circulation utilising an in vitro placental perfusion
      model. In all experiments, the vasculature of an isolated human placental
      cotyledon was pre-constricted with the thromboxane A2 mimetic U46619. A simple
      dose of PTHrP (1-34) or PTH (1-34) (1.7-300 nM) was then infused into the fetal
      placental circulation of the cotyledon. In other experiments, cotyledons were
      repeatedly infused with PTHrP (1-34) or PTH (1-34) (51.3 nM). Vasodilatory
      responses were significantly reduced in response to repeated exposure to PTHrP (1
      34) (P < 0.001), indicating that this peptide desensitizes the fetal-placental
      vasculature. PTHrP (1-34) and PTH (1-34) equipotently stimulated a significant
      vasodilation of the fetal-placental circulation (P < 0.0001). The PTHrP receptor
      antagonist [Asn10, Leu 11]PTHrP (7-34) (102 nM) was infused in U46619-constricted
      placentae in the presence and absence of PTHrP (1-34) (10.2 nM). The PTHrP
      antagonist alone had no significant effect in the fetal-placental circulation.
      The antagonist significantly attenuated the response to PTHrP (1-34) (P < 0.015).
      Based on the data obtained in this study it is suggested that locally produced
      PTHrP (1-34) may be involved in the regulation of normal human fetal-placental
      vascular tone in autocrine and/or paracrine fashion.

PMID- 9290156
TI  - Placental ratio--its relationship with mild maternal anaemia.
AB  - To determine whether placental ratio is influenced by maternal anaemia, a
      retrospective observational study was performed in a regional tertiary hospital
      in Hong Kong. The gestational age, birthweight, placental weight, and placental
      ratio were studied in 152 mothers with anaemia due to thalassaemia trait, 232
      mothers with anaemia due to iron deficiency, and 279 non-anaemic mothers as
      controls. All had singleton pregnancies. Compared to the control group, the iron
      deficiency group had higher placental weight (P = 0.001) and placental ratio (P <
      0.001) while the thalassaemia trait group had higher placental ratio (P = 0.011)
      and, after including gestational age as covariate for analysis, higher placental
      weight (P = 0.019) as well. There was, however, no difference in the placental
      weight or ratio between the two anaemia groups. The placental ratio was not
      correlated to the haemoglobin levels at booking, third trimester, or the lowest
      one, in any group, but it was correlated with these three haemoglobin levels with
      the three groups combined. Placental ratio was also correlated to gestational age
      in all groups. The results confirm the observation that the placental ratio is
      increased in anaemic pregnancies, and indicate that anaemia, rather than
      underlying iron deficiency, is the cause for an increased placental ratio.

PMID- 9290157
TI  - Hypoxia downregulates continuous and interleukin-1-induced expression of human
      chorionic gonadotropin in choriocarcinoma cells.
AB  - The effects of hypoxia on JEG-3, BeWo, and JAr cells were investigated and it was
      demonstrated that choriocarcinoma cells can be used as a model to study the
      molecular mechanism of hypoxia-mediated repression of human chorionic
      gonadotropin (hCG). Cells were maintained under hypoxia (3.5 per cent O2) for 72
      h without loss of variability, as demonstrated by the fact that 93-98 per cent of
      the cells excluded trypan blue. Up to 48 h, cell growth was not significantly
      influenced by hypoxia, and analysis by flow cytometry did not reveal major
      changes in cell cycle distribution. JEG-3, BeWo, and JAr cells which were grown
      for 48 h under hypoxia secreted 81, 67, and 71 per cent less hCG than cells
      cultivated under normoxic conditions. The extent of hCG reduction was dependent
      on the oxygen concentration. Moreover, release of the hormone from hypoxic JAr
      cells was not stimulated upon addition of interleukin-1 (IL-1). Treatment of JEG
      3 cells with methotrexate (MTX) led to a 4.3-fold augmentation in hCG secretion
      and to an increase in the amount of G0/G1 cells. However, when cells were
      cultured in the presence of MTX and hypoxia, hCG secretion decreased 10-fold and
      beta hCG mRNA declined to almost undetectable levels suggesting that
      downregulation of beta hCG mRNA is the major cause of diminished hCG release
      under hypoxic conditions.

PMID- 9290158
TI  - Ontogenetic and phylogenetic evaluation of the presence of fibrin-type fibrinoid
      in the villous haemochorial placenta.
AB  - The hypothesis that fibrin type fibrinoid deposition on villi is unique to the
      term human placenta was tested. Bright-field microscopy was used to examine
      sections of first and second trimester human placental villi and tissues from
      three animal species that have villous haemochorial placentae similar to the
      human: the armadillo, the baboon and the rhesus. Sections stained with
      haematoxylin and eosin showed fibrin type fibrinoid deposits were hypocellular,
      eosinophilic masses attached to the surface of villi examined from both the human
      and the animal species. The deposits were located at discontinuities in the
      syncytiotrophoblast layer, and the fibrinoid provided a matrix for trophoblast re
      epithelization of the villous surface. It is concluded that fibrin-type fibrinoid
      is not unique to the term human placenta. The presence of the syncytiotrophoblast
      discontinuities associated with the fibrinoid deposition must be considered in
      models of maternal-fetal exchange in the villous haemochorial placenta.

PMID- 9290159
TI  - The North American trophoblast meeting, San Diego, California, USA, 19 March
      1997.

PMID- 9290160
TI  - Renal accumulation and distribution of hyaluronan after ureteral obstruction.
AB  - In a unilateral ureteral obstruction model, a progressive accumulation of
      hyaluronan (HA) was observed in the renal papilla during the first 11 days of
      obstruction, after which the amount of HA decreased until the last day of
      observation, i.e. day 22. The initial accumulation of HA in the obstructed kidney
      probably reflects the attempts of the kidney to maintain osmotic balance.
      Consequently, when filtration ceases, HA synthesis decreases and the
      concentration of HA falls. In the papilla of the contralateral kidney, that had
      not been exposed to any mechanical damage, the HA content was found to vary in a
      similar way to that in the obstructed kidney. The explanation for this could be
      that the mesenchymal cells within the papilla increase their production of HA in
      order to meet the requirements of increased function necessary to also shoulder
      the function of the damaged kidney. In short similar variations in the HA content
      of the renal papilla was observed in both healthy and obstructed kidneys in a
      unilateral ureteral obstruction model.

PMID- 9290161
TI  - Intracorporeal pneumatic lithotripsy for ureteral and vesical calculi.
AB  - To evaluate the effectiveness of pneumatic lithotripsy, 92 patients with 98 lower
      or mid-ureteric calculi and 8 with vesical calculi were treated with pneumatic
      lithotripsy (Swiss Lithoclast) under spinal anaesthesia. Successful stone
      fragmentation was achieved in 96 patients. In two patients their stones migrated
      to the upper ureter and renal pelvis during the procedure and so they were
      referred for extra corporeal shock wave lithotripsy. Total ureteral avulsion
      occurred in one patient and in another case attempts to dilate the stenotic
      ureteral orifice failed. In both cases, ureterolithotomy and ureteral
      reimplantation were performed. Pneumatic lithotripsy is found to be an easy,
      reliable and cost-effective method of endoscopic lithotripsy.

PMID- 9290162
TI  - Bladder cancer in Estonia, 1968-1992: incidence, mortality, prevalence and
      survival.
AB  - This paper summarizes what is known about the occurrence and survival of bladder
      cancer in Estonia from 1968 to 1992. In 1988-92 the age standardized (world
      standard) incidence rate of bladder cancer was 11.1 per 100,000 person-years in
      males and 2.0 in females, and the age standardized mortality rate was 8.2 and
      2.7, respectively; by July 1, 1990 the age standardized prevalence rate was 41.5
      and 14.7, respectively. Between 1968-72 and 1988-92, incidence increased by 1.26
      times (95% confidence interval 1.09 to 1.46) among males; incidence rates for
      females did not show a consistent trend. The time trends in mortality generally
      paralleled the trends in incidence. Higher rates of bladder cancer were found
      among males in five large towns. For patients diagnosed in 1983-87, the five-year
      relative survival was 32.4% (95% confidence interval 27.0 to 37.8) for males and
      32.5% (23.8 to 41.2) for females; throughout the 20 years there was no
      improvement in survival. As the survival rates are less favorable than those in
      the Nordic countries, further hospital-based studies are needed to investigate
      the relation between survival and clinical characteristics.

PMID- 9290163
TI  - Effects of intravesical instillation of 5-fluorouracil and interferon in patients
      with recurrent superficial urinary bladder carcinoma. A clinical and
      pharmacodynamic study.
AB  - Eleven patients with recurrent superficial bladder tumours were treated with 6
      weekly instillations of 10 million IU Introna and 1000 mg 5-fluorouracil for 1 h.
      Before and immediately after the first treatment biopsies were taken from normal
      urothelium and tumour for analysis of thymidylate synthase (TS). One papillary
      tumour was left as a marker. Tumour tissue had 9 times higher TS concentrations
      than normal urothelium (0.97 versus 0.11 pmol/g, p < 0.005). Despite a large
      variation in TS concentration in the tumours between different patients (range
      0.02-2.24 pmol/g), after instillation the TS concentration decreased
      significantly in all but one patient. Six patients had complete and 2 had partial
      tumour regression after treatment. The effect was inversely correlated to the
      initial TS value. A low TS value seemed to predict a good response. The data
      suggest that weekly administrations are not sufficient in those with high TS
      concentrations. New treatment schedules may be beneficial in those with highly
      proliferating bladder tumours.

PMID- 9290164
TI  - Long-term results of the Stamey Bladder-neck suspension procedure and of the
      Burch colposuspension.
AB  - This retrospective study compares the long-term results of the Stamey bladder
      neck suspension and the Burch colposuspension following operation for urinary
      incontinence in women. A total of 182 women underwent operation for urinary
      incontinence: 83 by Stamey bladder-neck suspension and 99 by Burch
      colposuspension. The case records were perused and questionnaires were sent to
      the 169 women who were still alive: 129 women had no previous operation for
      urinary incontinence. At follow-up in this group a median of 7 years after the
      operation, 32% were completely continent and 39% had improved after the Stamey
      method, as against 33% and 29%, respectively, after Burch (p > 0.05). The Stamey
      operation was associated with a lower complication rate (12%) and a lower rate of
      re-operation (16%) than the Burch operation (23% and 22%, respectively) (p >
      0.05). Previous incontinence surgery and mixed type of incontinence was
      associated with poor outcome in the Stamey group.

PMID- 9290165
TI  - Relapses in early-stage testicular seminoma: radiation therapy versus
      retroperitoneal lymphadenectomy.
AB  - Being among the most radiosensitive tumours, radiation therapy has replaced
      retroperitoneal lymphadenectomy in the treatment of early-stage testicular
      seminoma. One hundred and sixty-one patients who were treated from 1975 through
      to 1991 with histologically confirmed testicular seminoma of stages I and II were
      analyses retrospectively. After high semicastration, 98 patients were treated by
      radiation therapy of regional lymph nodes and 63 patients received
      retroperitoneal lymphadenectomy. Until 1985 retroperitoneal lymphadenectomy was
      preferred, but after 1985 radiotherapy outweighed retroperitoneal
      lymphadenectomy. The follow-up ranged from 11 months to 13.5 years, with a median
      of 79 months. Retroperitoneally, in-field relapses occurred in 9.5% (6/63
      patients) after retroperitoneal lymphadenectomy and in 2.0% (2/98 patients) after
      radiation therapy (Fisher exact test, p = 0.057). A trend to a higher frequency
      of retroperitoneal relapses after retroperitoneal lymphadenectomy seemed to be
      apparent. Relapses outside the operation site or radiation fields were registered
      with non-significantly different frequencies (p = 0.741) of 4.8% (3/63 patients)
      and 7.1% (7/98 patients), respectively. Relapses increased from 4.1% for stage I
      (5/121 patients) up to 58.3% for stage IIC (7/12 patients).

PMID- 9290166
TI  - Sexual development in patients treated for cryptorchidism.
AB  - An analysis of sexual development was carried out in adult patients treated in
      childhood for cryptorchidism. Forty-seven healthy men served as a control group.
      The cryptorchid patients had been treated between the ages of 10 months to 13
      years and their ages ranged from 16 to 30 years at follow-up. The onset of
      puberty, and sexual development, were within normal limits in all patients,
      although spermarche occurred somewhat later in the patients than in the controls.
      In addition, the patients were on average slightly less sexually active than the
      controls. Neither age at the time of treatment nor the method of treatment
      correlated with current sexual activity. The patients with larger testes were,
      however, sexually more active. Both treatment age and the method of treatment,
      whether hormonal or surgical, should be selected on the basis of fertility
      prognosis.

PMID- 9290167
TI  - Lack of association between cystopathy and progression of diabetic nephropathy in
      insulin-dependent diabetes mellitus.
AB  - Whether an association exists between cystopathy and progression of diabetic
      nephropathy has never been clarified. The aim of the present study was to measure
      the degree of cystopathy in relation to the rate of progression of diabetic
      nephropathy. To that end, 17 insulin-dependent diabetic patients with diabetic
      nephropathy but without voiding symptoms were investigated urodynamically. The
      median age of the patients was 45 years (range 27-67 years), diabetes duration 23
      years (range 14-44 years) and the serum creatinine level was 162 mumol/L (median,
      range 65-449 mumol/L) at the time of the study. The progression rate of diabetic
      nephropathy was analysed retrospectively by measuring changes in yearly mean
      values of Log10 serum creatinine for a period of 13 years (3-15 years) before the
      investigation. The progression rate was 0.028 mumol/L/year (median). Patients
      with a progression rate above and below the median rate were considered to be
      rapid (n = 8) and slow (n = 9) progressors, respectively. More women than men had
      a rapid progression rate of nephropathy. Rapid progressors were found to have
      smaller volume or residual urine (90 vs 165 ml; p < 0.05), larger volume voided
      (440 vs 270 ml; p < 0.05), lower opening pressure (18 vs 48 cm H2O; p < 0.05) and
      lower pressure at maximum flow (37 vs 64 cm H2O; p < 0.05) compared to slow
      progressors. However, these variables were not related to the progression rate of
      nephropathy (MANOVA). Furthermore, these results should be interpreted with
      caution because of the natural gender differences in pressure conditions. In
      conclusion, rapid progression of diabetic nephropathy does not seem to be
      associated with dysfunction of the urinary bladder measured with cystometry and
      pressure flow.

PMID- 9290169
TI  - Non-infectious complications of continuous ambulatory peritoneal dialysis:
      evaluation with peritoneal computed tomography.
AB  - The purpose of the study was to evaluate the non-infectious complications of
      continuous ambulatory peritoneal dialysis (CAPD) using peritoneal computed
      tomography (PCT). Twenty symptomatic patients were included in the study.
      Initially 2000 ml of dialysate fluid was infused into the peritoneal cavity and
      standard peritoneal computed tomography (SPCT) serial scans with 10 mm thickness
      were performed from the mid-thoracic region to the genital organs. Afterwards,
      100 ml of non-ionic contrast material containing 300 mg/ml iodine was injected
      through the catheter and was distributed homogeneously in the intra-abdominal
      dialysate fluid by changing the positions of the patients; after waiting 2-4 h,
      the CT scan was released as peritoneal contrast computed tomography (PCCT). In
      patients (n = 20) both SPCT and PCCT revealed 90% (n = 18) pathological findings.
      But PCCT showed 60% (n = 12) additional pathological findings. We believe that
      PCT is beneficial for evaluation of non-infectious complications of CAPD. But
      PCCT is superior to SPCT in evaluating non-infectious complications encountered
      in patients on CAPD treatment.

PMID- 9290168
TI  - Lipid peroxidation and antioxidant activity in chronic haemodialysis patients
      treated with recombinant human erythropoietin.
AB  - In anaemia of chronic renal failure, the most important factor in the shortened
      erythrocyte survival may be lipid peroxidation of the cell membrane. Defective
      antioxidant activity may increase this damage. Although recombinant human
      erythropoietin (r-HuEPO) can effectively correct anaemia in chronic haemodialysis
      patients, its actions on lipid peroxidation and antioxidant activity are not
      clear. These actions were investigated in 13 patients undergoing chronic
      haemodialysis. Antioxidant activity, including red blood cell superoxide
      dismutase and total glutathione peroxidase levels and the lipid peroxidation
      product malondialdehyde, were measured before and 3 months after initiation of r
      HuEPO treatment, using heparinized venous whole blood for cell and plasma
      determinations. Age-matched healthy volunteers were controls. Significantly
      higher levels of superoxide dismutase and total glutathione peroxidase were found
      in the patients than in the controls (p < 0.01). Plasma malondialdehyde levels
      were not affected by r-HuEPO. The results are explained by erythropoiesis and
      cellular haemoglobin synthesis due to r-HuEPO, followed by increase of
      circulating young red cells. The membranes of these young cells contain more
      antioxidant enzymes than the others. Despite r-HuEPO treatment, plasma
      malondialdehyde levels in haemodialysis patients may be higher than normal
      because of the uraemic milieu and the chronic haemodialysis.

PMID- 9290170
TI  - Acetylsalicylic acid-induced bleeding disorder.

PMID- 9290171
TI  - Management of complete ureteral replacement. Experiences and review of the
      literature.
AB  - The common treatment for patients with extensive damage to the ureter is complete
      ureteral replacement, combining Boari flap-psoas bladder hitch and downward
      mobilization of the involved kidney, with complete ideal replacement of the
      ureter, renal autotransplantation, of elective nephrectomy. Three case reports
      serve to describe two options of reconstructive treatment for complete ureteral
      replacement. The operative techniques, their limits, their postoperative results,
      and the treatment alternatives are discussed with due regard to recent
      literature. In the case of ileal replacement we have used a very short ileal
      segment to reduce the absorption surface of the ileal mucosa. Reflux prevention
      of the ileal segment was performed by creating an invaginated distal ileum nipple
      which was additionally fixed at the Boari flap by a third stapler row (auto
      suture TASS) to prevent potential nipple-gliding.

PMID- 9290172
TI  - Synchronous bilateral testicular tumour: nonseminomatous germ cell tumours and
      contralateral benign tumours.
AB  - Synchronous bilateral testicular germ cell tumours (TGCT) of different origin are
      very rare; the simultaneous appearance of a TGCT with a contralateral benign non
      germ cell tumour represents an even more seldom event. We report on three
      patients with nonseminomatous TGCT and a contralateral benign testis tumour being
      Leydig cell tumour, leiomyoma and epidermopid cyst, respectively. Patients were
      treated by radical orchiectomy in one case and by enucleation resection of the
      tumour in two cases. After follow-up of more than 5 years all patients are NED;
      no local recurrence occurred in the patients treated by tumour enucleation with
      their endogenous testosterone production being maintained. Although very rare the
      simultaneous appearance of a malignant TGCT and a contralateral benign
      intratesticular mass should be considered with bilateral tumours. Frozen section
      examination of the tumours might enable an organ sparing approach in benign
      testis tumours thereby maintaining endogenous testosterone production and
      fertility.

PMID- 9290173
TI  - Combined malignant testicular tumor and splenogonadal fusion. A case story.
AB  - Splenogonadal fusion may be misinterpretated as a primary malignant testicular
      tumor or as an adenomatoid tumor. Knowledge of this entity is important in order
      to preserve the testis at surgery. A rare case of simultaneous occurrence of
      splenogonadal fusion and mixed malignant tumor of the testis is reported.

PMID- 9290175
TI  - Strangulation of the scrotum.
AB  - A man presented to our department showed scrotal swelling and beginning priapism
      due to a ball bearing ring. The patient had passed his scrotum through the metal
      ring eight years before. Now he has observed an increasing swelling for seven
      days. The condition had to be treated operatively.

PMID- 9290174
TI  - Urologic complications from a gunshot wound and the rare course of a bullet in
      the human body.
AB  - Presentation of the medical history of a patient who received a gunshot wound in
      the Second World War, and the rare course the bullet took from the time of impact
      until its removal 11 months later. The entrance point of the bullet was the left
      supraclavicular area of the thorax, and it was eventually removed from the
      patient's urethra.

PMID- 9290177
TI  - Entrapment neuropathy of the internal pudendal nerve. Report of two cases.
AB  - Entrapment neuropathy of the internal pudendal nerve in the Alcock canal is a
      rare entity and literature on the subject is lacking. The pathogenesis of this
      disease is probably related to repeated microtraumatisms of the perineal region
      acting on the Alcock canal or dysmetabolic diseases favouring compression of the
      pudendal nerve inside the Alcock canal. In this article two new cases which have
      come to our attention are described and literature on the topic, with special
      regard to diagnosis and treatment, is reviewed.

PMID- 9290176
TI  - Recurrent hemorrhage for ileal conduit: an uncommon complication of portal
      hypertension.
AB  - Massive hemorrhage from an ileal conduit is rare. We report who presented with
      massive recurrent hemorrhage from previously undiagnosed ileal conduit varices
      secondary to portal hypertension. Current methods for diagnosis and treatment of
      this rare but life threatening entity are discussed.

PMID- 9290178
TI  - Reno-colo-cutaneous fistula. A case report.
AB  - Reno-colo-cutaneous fistula due to genito-urinary tuberculosis is extremely rare.
      We describe one such case which was successfully managed by single stage surgery
      (nephroureterectomy, fistulectomy and primary repair of colon) and anti
      tubercular treatment.

PMID- 9290179
TI  - Giant megalo-ureter and duplex kidney in an asymptomatic adult.
AB  - An abdominal mass was palpated in an asymptomatic adult during a routine medical
      check-up. Ultrasonography and computed tomography scan diagnosed a simple renal
      cyst, a mesenteric cyst and a seminal vesicle cyst. At laparotomy a complete
      ureteral duplication and a giant ectopic megalo-ureter were diagnosed. Other
      complications were ruled out in the follow-up. Ureterectomy without
      heminephrectomy was performed and the patient remains asymptomatic 5 years after
      surgery.

PMID- 9290180
TI  - Epidemiology of colic.
AB  - Understanding the epidemiology of equine colic is directly relevant to the
      management of individual horses with colic. In this article, the epidemiology of
      colic is reviewed with emphasis on epidemiologic studies that have identified
      specific factors associated with increased risk of colic and epidemiologic
      studies that are designed to predict the need for surgery and prognosis in horses
      with colic. Despite the magnitude of the problem of equine colic, much remains to
      be learned about the epidemiology of this disease.

PMID- 9290181
TI  - Advances in diagnostic techniques for horses with colic.
AB  - Recent advances in the use of abdominal ultrasound, endoscopy, laparoscopy,
      radiography, and peritoneal fluid analysis have contributed to the evaluation of
      horses with colic. Improved diagnostic capabilities allow earlier surgical
      intervention when necessary, and this should improve survival rates and the
      economic aspects of case management.

PMID- 9290182
TI  - Adjunctive methods in equine gastrointestinal surgery.
AB  - The medical management of postoperative abdominal disorders remains a diagnostic
      and therapeutic challenge for the equine clinician. Recent advances in the
      development of techniques and medications to offset or attenuate ischemia
      reperfusion injury, endotoxemia, and ileus are encouraging and potentially will
      decrease the incidence of additional complications.

PMID- 9290184
TI  - Surgery of the small intestine.
AB  - Although earlier reports describe a poor prognosis for small intestinal surgery
      in the horse, there is growing evidence that the short-term survival rate can
      exceed 80%. In addition to advancements in surgery and aftercare, early referral
      contributes considerably to the improved prognosis. Surgical procedures that
      restore anatomic and physiologic continuity to close to normal can minimize
      postoperative complications. Jejunojejunostomy carries a better prognosis than
      jejunocecostomy, probably because the latter involves anastomosis between two
      intestinal segments with dissimilar functions. Careful technique can reduce the
      prevalence of complications, such as postoperative ileus and serosal adhesions.

PMID- 9290183
TI  - Treatment of impaction colics.
AB  - Impactions have been reported in the stomach and all segments of the intestine.
      Impactions predominately occur just oral to sites of intestinal narrowing or
      active pacemakers. The most common sites of impaction are in the ileum, the
      cecum, and the large colon pelvic flexure. The treatment of gastrointestinal
      impactions depends on the segment affected and the amount of bowel damage which
      has occurred from distension. Many impactions respond to appropriate
      administration of analgesics, cathartics, and oral or intravenous fluids. The
      prognosis for impactions treated medically is better than for those which require
      surgery.

PMID- 9290185
TI  - Diseases and surgery of the cecum.
AB  - The cecum is an important site of water and electrolyte absorption, as well as
      microbial digestion of soluble and insoluble carbohydrates. These functions of
      the cecum and ascending colon require that ingesta be mixed constantly and
      retained long enough to complete the digestion of cellulose. Parasites, changes
      in regional blood flow, diet, and various pharmacologic agents are associated
      with alterations in normal cecal motility patterns.

PMID- 9290186
TI  - Diseases and surgery of the large colon.
AB  - Displacements and intraluminal obstructions of the large colon carry a good to
      excellent prognosis for long-term recovery, and surgery for these diseases is
      rarely followed by short-term or long-term complications. Entrapment of the large
      colon over the renosplenic ligament is amenable to medical therapies so that
      surgery can be avoided in many cases. However, preoperative diagnosis of all
      nonstrangulating diseases of the large colon can be difficult. Vascular diseases
      of the large colon, such as thromboembolic diseases and large colon volvulus, are
      more difficult to treat and carry a poorer prognosis for survival.

PMID- 9290187
TI  - Large colon resection.
AB  - Strangulating large colon volvulus presents the surgeon with the dilemma of
      determining the extent of compromise to the affected tissue and the most
      appropriate surgical treatment of this tissue. This decision is complicated
      because there is a significant volvulus recurrence rate. Large colon resection
      and anastomosis is the most aggressive treatment option but prevents recurrence
      and may provide an alternative to euthanasia for some horses.

PMID- 9290188
TI  - Colopexy.
AB  - Colopexy is a surgical procedure designed to create an adhesion from the ventral
      colon to the body wall to prevent recurrence of large colon volvulus or
      displacement, and is a useful technique to prevent recurrence of this disease.
      Colopexies usually are reserved for broodmares, because this is the population of
      horses that is most predisposed to recurrence of large colon volvulus.

PMID- 9290189
TI  - Diseases and surgery of the small colon.
AB  - Diseases of the small colon are numerous and they can affect horses of any age.
      Diseases can be simple obstructions, nonstrangulating obstructions, strangulating
      obstructions, and congenital defects. American Miniature Horses appear prone to
      luminal obstruction with impacted intestinal contents, and some ischemic diseases
      are more common in postpartum mares. Enterotomy and enterectomy have a high
      success rate in the small colon, provided the affected portion can be
      exteriorized. The beginning and terminal portions of the small colon can be
      involved in many diseases and are not readily accessible from standard abdominal
      approaches. The prognosis is generally more favorable than has been proposed.

PMID- 9290190
TI  - Management of rectal tears.
AB  - Rectal tears have important medicolegal implications, and severe tears have a
      poor prognosis. Prompt diagnosis, immediate application of first aid measures,
      early referral, use of appropriate definitive treatments, and aggressive
      aftercare will improve the prognosis. The grade of rectal injury will determine
      the definitive treatment, but there are few guidelines to determine which
      treatment is best in each case. Bypass procedures, such as colostomy and
      indwelling rectal liner, have their own advantages and disadvantages, but can
      facilitate healing and prevent life-threatening complications if they are used
      with minimum delay. Suture of the tear can be difficult, but should be attempted
      to hasten healing and to prevent progression of the tear to a more severe injury.

PMID- 9290191
TI  - Abdominal surgery in foals.
AB  - Foals are good candidates for abdominal surgery because their smaller size
      permits a more complete abdominal exploration and frequently definitive
      procedures in many cases. The use of rectal examination is replaced with
      alternative diagnostic modalities such as barium contrast radiography and
      ultrasonography. With the advancements in these technologies they can distinguish
      common gastrointestinal lesions and, in most cases, provide sufficient
      information to guide surgical intervention. The unique aspects of diagnosis and
      surgical management of gastrointestinal disorders of the foal are discussed.

PMID- 9290192
TI  - Current concepts in management of abdominal adhesions.
AB  - Adhesions are an important complication after abdominal surgery in horses and
      foals, especially after small intestinal resection and anastomosis. Prevention
      therapies used in horses have included nonsteroidal anti-inflammatory drugs,
      antibiotics, heparin, dimethyl sulfoxide, carboxymethylcellulose, and meticulous
      surgical technique; however, the ideal surgical technique and prevention therapy
      has not been determined. Further, treatment of abdominal adhesions has a poor
      prognosis, emphasizing the need for improvements in prevention methods.

PMID- 9290193
TI  - 'Dramatic drop' in BSE cases.

PMID- 9290194
TI  - Comparison of five tests for the detection of antibodies against chlamydial
      (enzootic) abortion of ewes.
AB  - Five tests for antibodies against chlamydial (enzootic) abortion of ewes were
      compared using 255 sera from experimentally (group 1) or naturally (group 2)
      infected animals, flocks free of the disease (group 3) and individual animals
      testing positively by the complement fixation test but from flocks with no
      evidence of chlamydial abortion (group 4). Sera from five specific pathogen-free
      lambs vaccinated with two different subtypes of Chlamydia pecorum were also
      included (group 5). All tests used some form of processed culture of C psitiaci
      as antigen. Specificities, established with group 3 and 4 sera, ranged between 96
      per cent (ELISA using lipopolysaccharide antigen) and 59 per cent (Immunocomb).
      Reactions with group 5 sera suggested that the cause of false positive results in
      the field might be cross-reactive antibodies against the arthritogenic subtype of
      C pecorum. Sensitivities, established with groups 1 and 2 sera, ranged between 81
      per cent (Immunocomb) and 51 per cent (ELISA using solubilised protein antigen).
      The minimum sample sizes required to be 95 per cent certain of detecting at least
      five seropositives in two infected flocks (combined data) were 15 to 48,
      dependent on the test applied. The Western blot test, applied to a proportion of
      samples, yielded no false positives with group 3 sera but 31.7 per cent with
      group 4 sera. Thus, none of the tests in this comparison emerged as sufficiently
      satisfactory in all respects, suggesting that further improvements in chlamydial
      serology must come through the use of non-native antigens or in the form of a
      competitive ELISA.

PMID- 9290195
TI  - Effect of platelet-activating factor on bovine pulmonary function.
AB  - The objectives of this study were to determine whether the infusion of platelet
      activating factor would modify bovine pulmonary function, heart rate and platelet
      count and whether any such modifications could be antagonised by the prior
      intravenous injection of a specific antagonist (WEB 2086). In saline-pretreated
      calves, the respiratory rate, total lung resistance (RL) and maximal changes in
      transpulmonary pressure (delta Ptp) were significantly increased whereas lung
      dynamic compliance (CLdyn), tidal volume (VT), platelet count and heart rate were
      significantly decreased. The changes in RL, CLdyn, VT and delta Ptp were
      abolished by pretreatment with WEB 2086, whereas respiratory rate remained
      significantly increased to 125 per cent of the baseline value, but less than in
      the saline-pretreated calves in which it was 250 per cent of the baseline value.

PMID- 9290196
TI  - Infectious temporomandibular joint disease in the horse: computed tomographic
      diagnosis and treatment of two cases.
AB  - Diagnostic imaging and treatment of unilateral destructive temporomandibular
      joint disease in two horses is described and discussed. Computed tomography
      appeared to be the best imaging technique for these lesions. The disease can be
      followed by functional recovery after the infection has resolved.

PMID- 9290197
TI  - Natural adaption to pigs of a Taiwanese isolate of foot-and-mouth disease virus.

PMID- 9290198
TI  - Detection of ovine herpesvirus 2 in Kenyan sheep by polymerase chain reaction.

PMID- 9290199
TI  - Persistent scratching in Cavalier King Charles spaniels.

PMID- 9290200
TI  - Frozen tail or limber tail in working dogs.

PMID- 9290202
TI  - Abdominal distension in a cat.

PMID- 9290201
TI  - Clinical mastitis in dairy cows after 'blitz' therapy.

PMID- 9290203
TI  - Rabies and quarantine.

PMID- 9290204
TI  - Vacuole segregation in the Saccharomyces cerevisiae vac2-1 mutant: structural and
      biochemical quantification of the segregation defect and formation of new
      vacuoles.
AB  - The conditional vacuolar segregation mutant vac2-1 [Shaw and Wickner (1991) EMBO
      J. 10, 1741-1748] shifted to non-permissive temperature (37 degrees C), forms
      large-budded cells without a vacuole in the bud, and daughter cells without an
      apparent vacuole. Some cells still contain normal segregation structures.
      Structural and biochemical quantification of the segregation defect showed that
      (i) about 10% of the full-grown buds did not contain a vacuole, (ii) about 15% of
      the small cells washed out of a population growing in an elutriation chamber at
      37 degrees C, did not contain a visible vacuole, and (iii) 15% of the cells per
      generation lost carboxypeptidase Y activity after proteinase A depletion. Thus,
      10-15% of the daughter cells did not inherit vacuolar structures or vacuolar
      proteolytic activity from the mother cell. To investigate the fate of vacuole
      less daughters, these cells were isolated by optical trapping. The isolated cells
      formed colonies on agar plates that consisted of cells with normal vacuoles, both
      at 23 and 37 degrees C. Thus, the vacuole-less cells that failed to inherit
      proteolytic activities from the mother cell apparently give rise to progeny
      containing structurally normal vacuoles. Time-lapse experiments showed that
      vacuole-less daughter cells formed vacuolar vesicles that fused into a new
      vacuole within 30 min. Although new buds only emerged after a vacuole had formed
      in the mother cell, the temporary lack of a vacuole had little effect on growth
      rate. The results suggest that an alternative pathway for vacuole formation
      exists, and that yeast cells may require a vacuole of some minimal size to
      initiate a new round of budding.

PMID- 9290205
TI  - Accumulation of misfolded protein aggregates leads to the formation of russell
      body-like dilated endoplasmic reticulum in yeast.
AB  - RNAP-1, an aspartic proteinase from a filamentous fungus Rhizopus niveus, is
      secreted very efficiently in Saccharomyces cerevisiae. It is synthesized first as
      a precursor form with signal sequence and prosequence in its amino-terminus. Our
      previous study indicated that the prosequence of RNAP-I had important roles in
      its correct folding and secretion in yeast, and that a prosequence-deleted
      derivative of RNAP-I, delta pro, was not secreted but was retained and degraded
      in the yeast endoplasmic reticulum (ER). In the present study, we show that the
      accumulation of delta pro in the yeast ER caused elevated synthesis of ER
      resident chaperones, indicating that delta pro is recognized as an unfolded
      protein species in the ER. Our biochemical data demonstrated that delta pro
      formed aggregates which contained BiP, but not protein disulfide isomerase (PDI),
      in the ER. Immunoelectron microscopical analysis revealed that the delta pro
      aggregates were indeed visible as electron-dense regions in the ER and nuclear
      envelope. Such 'chaperone-associated misfolded protein bodies' were observed for
      the first time in yeast. Morphologies of the ER and nucleus were drastically
      altered by the accumulation of the delta pro aggregates. The ER lost its flat
      cisternal shape; the ER lumen extended aberrantly and the ER membrane irregularly
      proliferated. The misfolded delta pro proteins are probably sorted from the
      ordinary ER lumen to form the aggregates so that the ER function would not be
      grossly impaired, and the dilated ER may represent an ER subcompartment where the
      delta pro aggregates are degraded.

PMID- 9290206
TI  - In vivo mutational analysis of highly conserved amino acid residues of the small
      subunit Cpa1p of the carbamylphosphate synthetase of Saccharomyces cerevisiae.
AB  - The role of selected amino acid residues located in the putative catalytic domain
      and of two conserved histidine residues within the small subunit of the
      carbamylphosphate synthetase (CPS) specific to the arginine biosynthesis pathway
      of the yeast Saccharomyces cerevisiae was studied using site-directed mutagenesis
      to change all residues to aspartic acid. Carbamylphosphate synthesis catalysed by
      modified CPS was tested in vivo. The C264D, H307D and H349D mutants were unable
      to grow on minimal medium, indicating the importance of these three residues for
      efficient CPS activity, whereas, four other mutated residues located in the
      catalytic site (including a proline residue) do not affect the growth rate. These
      results in comparison to those obtained with the CPS of Escherichia coli,
      implicate residues Cys 264 and His 349 in the glutaminase catalytic activity, and
      His 307 in the binding of glutamine to the active site. Using these three
      defective mutants, we investigated the in vivo utilization of ammonia by CPS.
      C264D and H307D mutants are able to use ammonia as a substrate when provided in
      sufficiently high concentrations (up to 200 mM). The H349D mutant, however, did
      not grow even at ammonium sulfate concentrations above 400 mM, suggesting that
      this substitution is critical to NH3-dependent CPS activity although the ammonia
      binding site is presumably located within the large subunit of the enzyme.

PMID- 9290207
TI  - Two new S-phase-specific genes from Saccharomyces cerevisiae.
AB  - Two new yeast genes, ASF1 (Anti-Silencing Function) and ASF2, as well as a C
      terminal fragment of SIR3, were identified as genes that derepressed the silent
      mating type loci when overexpressed. ASF2 overexpression caused a greater
      derepression than did ASF1. ASF1 overexpression also weakened repression of genes
      near telomeres, but, interestingly, ASF2 had no effect on telomeric silencing.
      Sequences of these two genes revealed open reading frames of 279 and 525 amino
      acids for ASF1 and ASF2, respectively. The ASF1 protein was evolutionarily
      conserved, MCB motifs, sequences commonly present upstream of genes transcribed
      specifically in S phase, were found in front of both genes, and, indeed, both
      genes were transcribed specifically in the S phase of the cell cycle. While an
      asf2 mutant was viable and had no obvious phenotypes, an asf1 mutant grew poorly.
      Neither mutant exhibited derepression of the silent mating type loci. The asf1
      mutant was sensitive to methyl methane sulfonate, slightly UV-sensitive and
      somewhat deficient in minichromosome maintenance. It also lowered the restrictive
      temperature of a cdc13ts mutant. These phenotypes suggested a role for ASF1 in
      DNA repair and chromosome maintenance.

PMID- 9290209
TI  - Who's who among the Saccharomyces cerevisiae actin-related proteins? A
      classification and nomenclature proposal for a large family.
AB  - Inspection of the complete Saccharomyces cerevisiae genome sequence and analysis
      of the actin-related proteins (ARPs) found therein revealed seven proteins, in
      addition to the previously designated actin-related proteins Arp1, Arp2 and Arp3,
      which contained substantial blocks of conservation relative to a chosen sub-set
      of actins. We have ordered the new ARPs relative to this group of actins and
      propose to name the more distantly related ARP members, according to their amino
      acid identity and similarity, Arp4-Arp10. Most of these proteins appear to
      represent the first example of new classes of ARPs, each of which may have
      specific localization(s) and cellular function(s). Recently reported ARPs from
      other species have also been included in the phylogenetic tree derived from the
      overall alignment of 29 actins and 28 ARPs.

PMID- 9290208
TI  - Impairment of peroxisome degradation in Pichia methanolica mutants defective in
      acetyl-CoA synthetase or isocitrate lyase.
AB  - Single recessive mutations of the methylotrophic yeast Pichia methanolica acs1,
      acs2, acs3 and icl1 affecting acetyl-CoA synthetase and isocitrate lyase, and
      growth on ethanol as sole carbon and energy source, caused a defect in autophagic
      peroxisome degradation during exposure of methanol-grown cells to ethanol. As a
      control, a mutation in mdd1, which resulted in a defect of the 'malic' enzyme and
      also prevented ethanol utilization, did not prevent peroxisome degradation.
      Peroxisome degradation in glucose medium was unimpaired in all strains tested.
      Addition of ethanol to methanol-grown cells of acs1, acs2, acs3 and icl1 mutants
      led to an increase in average vacuole size. Thickening of peroxisomal membranes
      and tight contacts between groups of peroxisomes and vacuoles were rarely
      observed. These processes proceeded much more slowly than in wild-type or mdd1
      mutant cells incubated under similar conditions. No peroxisomal remnants were
      observed inside vacuoles in the cells of acs1, acs2, acs3 and icl1 mutants after
      prolonged cultivation in ethanol medium. We hypothesize that the acs and icl
      mutants are defective in synthesis of the true effector--presumably glyoxylate-
      of peroxisome degradation in ethanol medium. Lack of the effector suspends
      peroxisome degradation at an early stage, namely signal transduction or
      peroxisome/vacuole recognition. Finally, these defects in peroxisome degradation
      resulted in mutant cells retaining high levels of alcohol oxidase which further
      led to increased levels of acetaldehyde accumulation upon incubation of mutant
      cells with ethanol.

PMID- 9290210
TI  - The effect of a suppressed rad52 mutation on the suppression of rad6 by srs2.
AB  - We have cloned a suppressor of a temperature-sensitive rad52 allele and found it
      to be a mutation in PUP1, a gene encoding a protease subunit of the 20s
      proteasome. This identity prompted us to examine the interrelationship among
      PUP1, RAD52, SRS2 and RAD6 because srs2 mutations not only suppress some rad52
      mutations but also suppress deletions of rad6, a gene encoding a protein in the
      ubiquination-dependent proteolysis pathway. We have found that while srs2
      suppresses the UV sensitivity of rad6 in the presence of RAD52, srs2 cannot
      suppress rad6 when the temperature-sensitive allele of rad52 is present. This
      inability of srs2 to suppress rad6 is irrespective of the incubation temperature
      or whether pup1 is suppressing the temperature-sensitive rad52 mutation.

PMID- 9290213
TI  - Current awareness on yeast.

PMID- 9290211
TI  - Heterologous HIS3 marker and GFP reporter modules for PCR-targeting in
      Saccharomyces cerevisiae.
AB  - We have fused the open reading frames of his3-complementing genes from
      Saccharomyces kluyveri and Schizosac-charomyces pombe to the strong TEF gene
      promotor of the filamentous fungus Ashbya gossypii. Both chimeric modules and the
      cognate S. kluyveri HIS3 gene were tested in transformations of his3 S.
      cerevisiae strains using PCR fragments flanked by 40 bp target guide sequences.
      The 1.4 kb chimeric Sz. pombe module (HIS3MX6) performed best. With less than 5%
      incorrectly targeted transformants, it functions as reliably as the widely used
      geniticin resistance marker kanMX. The rare false-positive His+ transformants
      seem to be due to non-homologous recombination rather than to gene conversion of
      the mutated endogenous his3 allele. We also cloned the green fluorescent protein
      gene from Aequorea victoria into our pFA-plasmids with HIS3MX6 and kanMX markers.
      The 0.9 kb GFP reporters consist of wild-type GFP or GFP-S65T coding sequences,
      lacking the ATG, fused to the S. cerevisiae ADH1 terminator. PCR-synthesized 2.4
      kb-long double modules flanked by 40-45 bp-long guide sequences were successfully
      targeted to the carboxy-terminus of a number of S. cerevisiae genes. We could
      estimate that only about 10% of the transformants carried inactivating mutations
      in the GFP reporter.

PMID- 9290212
TI  - Sequence analysis of 203 kilobases from Saccharomyces cerevisiae chromosome VII.
AB  - The nucleotide sequences of five major regions from chromosome VII of
      Saccharomyces cerevisiae have been determined and analysed. These regions
      represent 203 kilobases corresponding to approximately one-fifth of the complete
      yeast chromosome VII. Two fragments originate from the left arm of this
      chromosome. The first one of about 15.8 kb starts approximately 75 kb from the
      left telomere and is bordered by the SK18 chromosomal marker. The second fragment
      covers the 72.6 kb region between the chromosomal markers CYH2 and ALG2. On the
      right chromosomal arm three regions, a 70.6 kb region between the MSB2 and the
      KSS1 chromosomal markers and two smaller regions dominated by the KRE11 marker
      and another one in the vicinity of the SER2 marker were sequenced. We found a
      total of 114 open reading frames (ORFs), 13 of which were completely overlapping
      with larger ORFs running in the opposite direction. A total of 44 yeast genes,
      the physiological functions of which are known, could be precisely mapped on this
      chromosome. Of the remaining 57 ORFs, 26 shared sequence homologies with known
      genes, among which were 13 other S. cerevisiae genes and five genes from other
      organisms. No homology with any sequence in the databases could be found for 31
      ORFs. Furthermore, five Ty elements were found, one of which may not be
      functional due to a frame shift in its Ty1B amino acid sequence. The five
      chromosomal regions harboured five potential ARS elements and one sigma element
      together with eight tRNA genes and two snRNAs, one of which is encoded by an
      intron of a protein-coding gene.

PMID- 9290214
TI  - Homeoboxes in sea anemones (Cnidaria:Anthozoa): a PCR-based survey of
      Nematostella vectensis and Metridium senile.
AB  - Homeobox genes belong to a phylogenetically widespread family of regulatory genes
      that play important roles in pattern formation and cell-fate specification in
      several model systems (e.g., Drosophila, mouse, and C. elegans). Although the
      evolution of many classes of homeobox genes predates the diversification of the
      Bilateria, comparatively little is known about homeobox genes in outgroups to the
      Bilateria, such as the Cnidaria. We used the polymerase chain reaction to recover
      12 partial homeoboxes from 2 species of sea anemones, Metridium senile and
      Nematostella vectensis (phylum Cnidaria; class Anthozoa). These homeoboxes appear
      to represent 9 distinct, mutually paralogous homeobox genes, 5 of which belong to
      previously identified cnidarian homeobox classes, and 4 of which appear to
      represent previously unidentified classes. The evolutionary relationships between
      the homeodomains of sea anemones and of bilaterian animals were assessed through
      database searches and phylogenetic analyses. As many as 5 of the anemone
      homeoboxes may belong to the Hox class, which suggests that the Hox gene
      complement of cnidarians is larger than previously expected. Homologs of the even
      skipped gene of Drosophila were also identified in both Metridium and
      Nematostella.

PMID- 9290215
TI  - Identification and localization of a possible rhodopsin in the echinoderms
      Asterias forbesi (Asteroidea) and Ophioderma brevispinum (Ophiuroidea).
AB  - Protein extracts of optic cushion tissue from the asteroid Asterias forbesi and
      arm tissue from the ophiuroid Ophioderma brevispinum were subjected to Western
      blot analysis. Both tissues contain a membrane-associated protein that reacts
      with two monoclonal antibodies raised against bovine rhodopsin. This protein
      migrates slightly behind bovine rhodopsin during sodium-dodecyl-sulfate
      polyacrylamide gel electrophoresis, suggesting that its molecular weight is
      slightly larger. Immunohistochemical examination of the optic cushions of A.
      forbesi revealed a substance that reacts with both monoclonal antibodies;
      moreover, this substance is more abundant in dark-adapted animals than in light
      adapted animals. The arms and central disk of O. brevispinum were also examined
      immunohistochemically. The tips of the arm spines contain a substance that reacts
      with both monoclonal antibodies, and at higher magnification this immunoreactive
      material is localized to small regions within the stroma of the ossicles. Taken
      together, the biochemical and immunochemical evidence suggests that the cross
      reacting protein is homologous to other known rhodopsins and is serving as a
      visual pigment in echinoderms.

PMID- 9290216
TI  - Early stopping to accept H(o) based on conditional power: approximations and
      comparisons.
AB  - It is intuitively appealing to clinicians to stop a trial early to accept the
      null hypothesis Ho if it appears that this will be the likely outcome at the
      planned end of the trial. We consider procedures that calculate at each time
      point the conditional probability of rejecting Ho at the end of the trial given
      the current data and some value of the parameter of interest. Lan, Simon, and
      Halperin (1982, Communications in Statistics C1, 207-219) calculate this
      probability under the design alternative, and Pepe and Anderson (1992, Applied
      Statistics 41, 181-190) use an alternative based solely on the current data. We
      investigate a modification to Pepe and Anderson's (1992) procedure that has a
      more satisfying interpretation. We define all of these procedures as formal
      sequential tests with lower stopping boundaries and study them in this context.
      This facilitates an improved understanding of the interplay of parameters by
      introducing visual displays, and it leads to an approximation for power by
      treating it as a boundary crossing probability. We use these tools to compare the
      performances of the different designs under a variety of parameter
      configurations.

PMID- 9290217
TI  - Fieller's theorem, Scheffe simultaneous confidence intervals, and ratios of
      parameters of linear and nonlinear mixed-effects models.
AB  - The issue of joint confidence region and simultaneous confidence interval
      estimation for ratios of the parameters of a nonlinear mixed-effects model is
      addressed using a Fieller's theorem approach. The method presented is similarly
      applicable to linear mixed-effects models. In addition, previous work on linear
      fixed-effects models is demonstrated to be a special case of the present method.
      The methodology is applied to the ratios of slopes in a study of gestational
      maturation of placental glucose transfer capacity in sheep.

PMID- 9290218
TI  - A likelihood-based approach to the estimation of relative DNA copy number by
      comparative genomic hybridization.
AB  - A general approach is described for efficiently and objectively analyzing
      comparative genomic hybridization (CGH) profile data based on the use of
      realistic statistical models and the application of standard likelihood-based
      inference. In contrast to other methods in current use, the approach provides a
      most parsimonious explanation by identifying the smallest number of relative DNA
      copy number changes consistent with the data, together with estimates of their
      levels and positions and of their standard errors. By making efficient use of
      available data, it has the potential to enhance the resolution of CGH technology.
      The computational feasibility of the method is illustrated by application to real
      CGH profile data from human chromosome 4.

PMID- 9290219
TI  - Weighted estimating equations with nonignorably missing response data.
AB  - We propose weighted estimating equations for data with nonignorable nonresponse
      in order to reduce the bias that can occur with a complete case analysis. A
      survey concerning medical practice guidelines, malpractice litigation, and
      settlement provides the framework. The survey was sent to recipients in two
      waves: those who responded on the first or second wave are used to estimate a
      nonignorable nonresponse model, while the fraction of recipients who never
      responded is used to allow the percentage of missing data to change with each
      wave. We use the structure of the GEE of Liang and Zeger (1986, Biometrika 73, 13
      22), adding weights equal to the inverse probability of being observed. We
      present simulations demonstrating the bias that can occur with an unweighted
      analysis and use the survey data to illustrate the methods.

PMID- 9290220
TI  - Modification of the Greenwood formula for correlated response times.
AB  - Life-table methodology for interval-censored survival times is used to estimate
      marginal survival probabilities from data consisting of independent cohorts of
      correlated responses. We restrict our attention to situations where response
      times within cohorts are exchangeable and the marginal survival distributions are
      the same for all individuals within any cohort. A modification of the Greenwood
      formula is derived for estimating variances and covariances of the estimates of
      the marginal survival probabilities. Simulation results show that this formula
      provides accurate adjustments for within-cohort correlations in finite samples.
      Comparisons with a nonparametric maximum likelihood estimator indicate negligible
      loss in efficiency from using simple life-table estimators of marginal survival
      probabilities that ignore the within-cohort correlations. Data from an
      angioplasty study where more than one procedure is performed on some patients are
      used to illustrate this methodology.

PMID- 9290221
TI  - Generalized covariance-adjusted discriminants: perspective and application.
AB  - When discriminant analysis is used in practice for assessing the usefulness of
      diagnostic markers, the lack of control over covariates motivates the need for
      their adjustment in the analysis. This necessity for adjustment arises especially
      when the researcher's aim is classification based on a set of diagnostic markers
      and is not based on a set of covariates for which there exists known
      heterogeneity among the subjects with respect to the groups under consideration.
      The traditional covariance-adjusted approach is restrictive for such applications
      in that they assume linear covariates and a normal distribution for the the
      feature vector. Further, there is no available method for variable selection in
      using such covariance-adjusted models. In this paper, we generalize the
      traditional covariance-adjusted model to a general normal and logistic model,
      where these generalized models not only relax the distributional assumptions on
      the feature vector but also allow for nonlinear covariates. Exact and asymptotic
      tests are also derived for the problem of variable selection for these new
      models. The methodology is illustrated with both simulated data and an actual
      data set from a psychiatric study on using the Social Rhythm Metric for patients
      with anxiety disorders.

PMID- 9290222
TI  - Linear mixed models with heterogeneous within-cluster variances.
AB  - This paper describes an extension of linear mixed models to allow for
      heterogeneous within-cluster variances in the analysis of clustered data.
      Unbiased estimating equations based on quasilikelihood/pseudolikelihood and
      method of moments are introduced and are shown to give consistent estimators of
      the regression coefficients, variance components, and heterogeneity parameter
      under regularity conditions. Cluster-specific random effects and variances are
      predicted by the posterior modes. The method is illustrated through an analysis
      of menstrual diary data and its properties are evaluated in a simulation study.

PMID- 9290224
TI  - Sample size calculations for studies with correlated observations.
AB  - Correlated data occur frequently in biomedical research. Examples include
      longitudinal studies, family studies, and ophthalmologic studies. In this paper,
      we present a method to compute sample sizes and statistical powers for studies
      involving correlated observations. This is a multivariate extension of the work
      by Self and Mauritsen (1988, Biometrics 44, 79-86), who derived a sample size and
      power formula for generalized linear models based on the score statistic. For
      correlated data, we appeal to a statistic based on the generalized estimating
      equation method (Liang and Zeger, 1986, Biometrika 73, 13-22). We highlight the
      additional assumptions needed to deal with correlated data. Some special cases
      that are commonly seen in practice are discussed, followed by simulation studies.

PMID- 9290223
TI  - Assessing the effects of interventions using longitudinal data with samples
      subject to selection.
AB  - Consider an uncontrolled study in which subjects are selected to start a new
      intervention because one or more previous measurements of a variable are within a
      particular range. Our aim is to use the repeated values obtained prior and
      subsequent to the start of the intervention to assess the effects of its
      introduction. However, because selection is based on the same variable as is
      being used to assess efficacy, regression to the mean will confound the
      interpretation of the results. In this paper, we present a likelihood-based
      method for evaluating the effects of the intervention using the repeated
      measurements while adjusting for the effects of the selection. The method uses a
      linear model to describe each subject's pattern of responses before and after the
      start of the new intervention. Additionally, it assumes that the effect of
      starting the new intervention on an individual's intercept and slope is the same
      for all subjects. However, no distributional assumption is made about the pattern
      of the linear model across subjects, thus making it particularly appropriate for
      phase I/II studies when patient histories on those not selected for the study are
      not available.

PMID- 9290225
TI  - Latent variable modeling of diagnostic accuracy.
AB  - Latent class analysis has been applied in medical research to assessing the
      sensitivity and specificity of diagnostic tests/diagnosticians. In these
      applications, a dichotomous latent variable corresponding to the unobserved true
      disease status of the patients is assumed. Associations among multiple diagnostic
      tests are attributed to the unobserved heterogeneity induced by the latent
      variable, and inferences for the sensitivities and specificities of the
      diagnostic tests are made possible even though the true disease status is
      unknown. However, a shortcoming of this approach to analyses of diagnostic tests
      is that the standard assumption of conditional independence among the diagnostic
      tests given a latent class is contraindicated by the data in some applications.
      In the present paper, models incorporating dependence among the diagnostic tests
      given a latent class are proposed. The models are parameterized so that the
      sensitivities and specificities of the diagnostic tests are simple functions of
      model parameters, and the usual latent class model obtains as a special case.
      Marginal models are used to account for the dependencies within each latent
      class. An accelerated EM gradient algorithm is demonstrated to obtain maximum
      likelihood estimates of the parameters of interest, as well as estimates of the
      precision of the estimates.

PMID- 9290226
TI  - Log-linear modeling with the negative multinomial distribution.
AB  - We develop a negative multinomial sampling plan in which observed cell counts are
      positively correlated. We show that maximum likelihood estimates of cell means
      are the same as those found under independent Poisson sampling. There is no
      maximum likelihood estimate for the shape parameter in general. We propose an
      estimate of the shape parameter based on the mean and quantiles of Pearson's chi
      squared statistic. These techniques are applied to models of cancer incidence for
      three cities in Ohio and longitudinal health care utilization by a group of
      senior citizens.

PMID- 9290227
TI  - Evaluation of confounding effects in ROC studies.
AB  - In many clinical studies, it is clear that external forces can affect the
      performance of diagnostic tests, as these factors influence the distributions of
      separator variables. A new estimator for the receiver operating characteristic
      (ROC) function is proposed; this estimator converges to the ROC function
      uniformly on the interval [0,1]. Using this new estimator, the author proposes to
      use Cox's proportional hazards regression model for the evaluation of confounding
      effects in ROC studies. The method can be used even when concomitant information
      is only available for the cases, for example, disease severity. A textbook
      example on prostate cancer is described for illustration.

PMID- 9290228
TI  - A detailed evaluation of adjustment methods for multiplicative measurement error
      in linear regression with applications in occupational epidemiology.
AB  - It is often appropriately assumed, based on both theoretical and empirical
      considerations, that airborne exposures in the workplace are lognormally
      distributed, and that a worker's mean exposure over a reference time period is a
      key predictor of subsequent adverse health effects for that worker.
      Unfortunately, it is generally impossible to accurately measure a worker's true
      mean exposure. We begin by introducing a familiar model for exposure that views
      this true mean, as well as logical surrogates for it, as lognormal random
      variables. In a more general context, we then consider the linear regression of a
      continuous health outcome on a lognormal predictor measured with multiplicative
      error. We discuss several candidate methods of adjusting for the measurement
      error to obtain consistent estimators of the true regression parameters. These
      methods include a simple correction of the ordinary least squares estimator based
      on the surrogate regression, the regression of the outcome on the covariates and
      on the conditional expectation of the true predictor given the observed
      surrogate, and a quasi-likelihood approach. By means of a simulation study, we
      compare the various methods for practical sample sizes and discuss important
      issues relevant to both estimation and inference. Finally, we illustrate
      promising adjustment strategies using actual lung function and dust exposure data
      on workers in the Dutch animal feed industry.

PMID- 9290229
TI  - Analyzing bivariate continuous data grouped into categories defined by empirical
      quantiles of marginal distributions.
AB  - Epidemiologists sometimes study the association between two measurements of
      exposure on the same subjects by grouping the original bivariate continuous data
      into categories that are defined by the empirical quantiles of the two marginal
      distributions. Although such grouped data are presented in a two-way contingency
      table, the cell counts in this table do not have a multinomial distribution. We
      describe the joint distribution of counts in such a table by the term empirical
      bivariate quantile-partitioned (EBQP) distribution. Blomqvist (1950, Annals of
      Mathematical Statistics 21, 539-600) gave an asymptotic EBQP theory for bivariate
      data partitioned by the sample medians. We demonstrate that his asymptotic theory
      is not correct, however, except in special cases. We present a general asymptotic
      theory for tables of arbitrary dimensions and apply this theory to construct
      confidence intervals for the kappa statistic. We show by simulations that the
      confidence interval procedures we propose have near nominal coverage for sample
      sizes exceeding 60 for both 2 x 2 and 3 x 3 tables. These simulations also
      illustrate that the asymptotic theory of Blomqvist (1950) and the methods that
      Fleiss, Cohen, and Everitt (1969, Psychological Bulletin 72, 323-327) give for
      multinomial tables can yield subnominal coverage for kappa calculated from EBQP
      tables, although in some cases the coverage for these procedures is near nominal
      levels.

PMID- 9290230
TI  - A generalized estimating equation approach for modeling random length binary
      vector data.
AB  - A common measure in clinical trials and epidemiologic studies is the number of
      events such as seizures, hospitalizations, or bouts of disease. Frequently, a
      binary measure of severity for each event is available but is not incorporated in
      the analysis. This paper proposes methodology for jointly modeling the number of
      events and the vector of correlated binary severity measures. Our formulation
      exploits the notion that a given covariate may affect both outcomes in a similar
      way. We functionally link the regression parameters for the counts and binary
      means and discuss a generalized estimating equation (GEE) approach for parameter
      estimation. We discuss conditions under which the proposed joint modeling
      approach provides marked gains in efficiency relative to the common procedure of
      simply modeling the counts, and we illustrate the methodology with epilepsy
      clinical trial data.

PMID- 9290231
TI  - Methods for comparing the means of two independent log-normal samples.
AB  - Standard methods of using the t-test and the Wilcoxon test have deficiencies for
      comparing the means of two skewed log-normal samples. In this paper, we propose
      two new methods to overcome these deficiencies: (1) a likelihood-based approach
      and (2) a bootstrap-based approach. Our simulation study shows that the
      likelihood-based approach is the best in terms of the type I error rate and power
      when data follow a log-normal distribution.

PMID- 9290232
TI  - Modelling memory in coal tits: an illustration of the EM algorithm.
AB  - Some species of birds are known to use memory to retrieve previously stored food.
      A series of experiments on one of those species, coal tits, investigated various
      aspects of such memory. For one particular experiment, a number of statistical
      models describing the memory were fitted. However, some of the data were
      unavoidably incomplete. The expectation maximization (EM) algorithm provides a
      means of incorporating the incomplete data into the fitting procedure.

PMID- 9290233
TI  - Global measures of local influence for proportional hazards regression models.
AB  - Cox proportional hazards regression models have been extended to multiple failure
      times and other situations by using a robust covariance matrix instead of the
      usual inverse of the information matrix. We modify an existing measure of
      individual influence by substituting the robust covariance matrix for the inverse
      of the information matrix. This provides a scalar measure of influence with known
      mean and bounded range on the interval (0,1). The measure is applicable to
      marginal multiple failure time models. Two examples are presented.

PMID- 9290234
TI  - Test for linear trend in 2 x K ordered tables with open-ended categories.
AB  - A method of evaluating trend (positive or negative) in 2 x K ordered tables is
      suggested for cases in which the scores for the first (K-1) categories are known
      a priori but the score for the last category is not known. Such a category is
      termed as open-ended category in this paper. Ordered tables with an open-ended
      category are often encountered while evaluating the Cochran-Armitage-Mantel (CAM)
      trend. In the present paper, the distribution of the test statistic is presented
      and simulations are carried out to check the asymptotics. The method is then
      exemplified by an existing data set.

PMID- 9290235
TI  - Estimating the generalized impact fraction from case-control data.
AB  - The generalized impact fraction (also called the generalized attributable
      fraction) was introduced by Walter (1980, American Journal of Epidemiology 112,
      409-416) and Morgenstern and Bursic (1982, Journal of Community Health 7, 292
      309) as a measure that generalizes the population attributable fraction
      (attributable risk). It is defined as the fractional reduction of a disease
      resulting from changing the current distribution of a risk factor to some
      modified distribution. We show that the point and variance estimator derived by
      Greenland and Drescher (1993, Biometrics 49, 865-872) for fixed shift functions
      can be extended to situations where the shift is a probabilistic function of the
      actual exposure value. The formulas are applicable for case-control designs where
      the cases are simply randomly selected and the controls are chosen in one of
      three ways: simple random sampling, stratified random sampling, and frequency
      matching.

PMID- 9290236
TI  - Orthographic analogies and developmental dyslexia.
AB  - Goswami (1986, 1988) has demonstrated that children can use orthographic
      analogies (particularly at the onset-rime level) between the spelling patterns in
      words to help to decode new words (e.g. using 'beak' to read 'peak'). This
      strategy has been shown in children as young as six years old. Since it is known
      that children with developmental dyslexia find it particularly difficult to read
      words that they have not been specifically taught (Lovett, Warren-Chaplin, Ransby
      & Borden, 1990), the present study investigated whether dyslexic children might
      be unable to use analogies. Employing a design similar to that used by Goswami
      (1988), it was hypothesized that dyslexics would find it difficult to transfer
      spontaneously knowledge of a 'clue' word to decode new words that could be read
      by analogy with the clue word. The results of Expt 1 indicated that the dyslexic
      readers read significantly fewer of the analogous words than a reading age
      matched comparison group of younger children. Furthermore, none of the nine
      dyslexic children read as many of the analogous words as the lowest scoring
      control child. In a second experiment, a design similar to that of Muter,
      Snowling & Taylor (1994) was used with a new and larger sample of dyslexic
      children. In this experiment, all the children were brought to criterion in
      reading the clue words before the analogous words were presented. Once again, the
      dyslexic children read significantly fewer words that were analogous with the
      clue words than did a reading age-matched comparison group. The number of
      analogous words that the dyslexic children read was significantly correlated with
      their performance on a test that is sensitive to the ability to detect rhyme. It
      is argued that a failure to make analogies may be one of the main causes of the
      reading impairment experienced by children with developmental dyslexia.

PMID- 9290237
TI  - A comparison of the encoding of content and order in olfactory memory and in
      memory for visually presented verbal materials.
AB  - The claim that there is no olfactory short-term memory store, as olfactory serial
      position (SP) effects are absent (Engen, 1987, 1989; Lawless & Engen, 1977),
      raises the issue whether memory for sensory qualities is differently organized
      from memories for more cognitive materials in vision and hearing. Early memory
      processing in olfaction is re-examined by comparing the results of similarly
      designed experiments which examine short-term memory for words and consonants,
      and for odours. Memory for content and memory for order were separately examined
      in each case. Serial position functions were obtained both for visually presented
      verbal materials and for odours. The serial position effects for content and
      order memory in both modalities are sufficiently similar in pattern to support
      the conclusion that short-term memory processing of olfactory and verbal stimuli
      is conducted by analogous memory mechanisms.

PMID- 9290238
TI  - A cross-cultural study of colour grouping: evidence for weak linguistic
      relativity.
AB  - We report a cross-cultural study of colour grouping carried out as a test of the
      Sapir-Whorf hypothesis (linguistic relativity theory). Speakers of English,
      Russian and Setswana-languages that differ in their number of basic colour terms,
      and in how the blue-green region is categorized--were compared on a colour
      sorting task. Informants sorted a representative set of 65 colours into groups so
      that members of the groups looked similar to each other, with no restriction on
      the number of groups formed. If linguistic relativity theory is true, then there
      should be reliable differences between the three samples in the composition of
      the groups they formed associated with the differing positions of colour category
      boundaries in the languages. The most striking feature of the results,
      inconsistent with linguistic relativity theory, was the similarity amongst the
      patterns of choice of the three samples. However, there were also significant
      differences amongst the samples. Setswana speakers (who have a single basic term
      for BLUE or GREEN) were more likely to group BLUE colours with GREEN colours than
      either English or Russian speakers. But Russian speakers (who have two basic
      colour terms for BLUE) were no more likely than English speakers to group light
      and dark BLUE separately. In addition there were general structural differences
      in grouping among the samples: they differed in the level of consensus in
      grouping, the number of groups formed and in the distribution of the number of
      colours placed in a group. These structural differences may reflect differences
      in the availability and salience of the colour categories across the languages.
      Our data support perceptual universalism modulated by weaker linguistic effects.

PMID- 9290239
TI  - Hemiregional variations in facial expression of emotions.
AB  - This study examined expressiveness of facial regions during posed expressions of
      two basic emotions: happy and sad. Two types of composite photographs were
      prepared: hemifacial composites of left-left (LL) or right-right (RR); and
      hemiregional composites involving a left-left composite in the upper part and a
      right-right composite in the lower part (LL/RR) of the face or vice versa
      (RR/LL). Participants ranked photographs of an emotion expression: normal
      orientation (RL), mirror reversed (LR), left facial composite (LL), right facial
      composite (RR) and hemiregional composites (RR/LL; LL/RR), in order of
      expressiveness. The hemiregional composite RR/LL was judged as most expressive
      followed by LL. The findings are explained in terms of the neuroanatomy of fibre
      projections from the left and right cerebral hemispheres to the facial muscles.

PMID- 9290240
TI  - The genome and genes of Neurospora crassa.
AB  - Neurospora crassa is an organism with a 7-decade contribution to genetic
      research. in a genome of 42.9 Mb and just over 1000 map units, to date over 800
      different genes have been identified by phenotype and/or map location, and 222
      genes have been characterized by sequencing. Methods by which analysis of the
      genome has been carried out are discussed, including linkage, RFLP, and
      chromosome walking. Characterized centomeres, telomeres, the nucleolar organizer
      and the dispersed 5S rRNA genes are discussed. Analysis of the protein-encoding
      genes is undertaken, using new software for the querying of standard sequence
      databases. Gene analysis includes consensus sequences for transcription and RNA
      splicing and new insights into codon usage.

PMID- 9290241
TI  - Cloning heterologous genes: problems and approaches.
AB  - Model fungi such as Neurospora crassa, Aspergillus niger, and Saccharomyces
      cerevisiae have provided a wealth of genetic information and are currently the
      object of cooperative genome sequencing projects. Many agriculturally and
      medically economic important pathogenic fungi, however, are less well
      characterized, which makes it difficult to study their genes and gene products.
      Gene sequences from model fungi offer a unique opportunity to clone cognate genes
      from pathogenic counterparts. In this review, we propose three basic strategies
      for cloning such genes: Functional complementation, sequence similarity, and
      genetic linkage. These strategies involve Southern hybridization, cloning,
      library screening, genetic complementation, and the polymerase chain reaction. We
      review the major problems encountered using these strategies and outline useful
      solutions to these difficulties.

PMID- 9290242
TI  - The design of pooling experiments for screening a clone map.
AB  - We consider nonadaptive pooling designs for unique-sequence screening of a 1530
      clone map of Aspergillus nidulans. The map has the properties that the clones
      are, with possibly a few exceptions, ordered and no more than 2 of them cover any
      point on the genome. We propose two subdesigns of the Steiner system S(3, 5, 65),
      one with 65 pools and approximately 118 clones per pool, the other with 54 pools
      and about 142 clones per pool. Each design allows 1 or 2 positive clones to be
      detected, even in the presence of substantial experimental error rates. More
      efficient designs are possible if the overlap information in the map is
      exploited, if there is no constraint on the number of clones in a pool, and if no
      error tolerance is required. An information theory lower bound requires at least
      12 pools to satisfy these minimal criteria, and an "interleaved binary" design
      can be constructed on 20 pools, with about 380 clones per pool. However, the
      designs with more pools have important properties of robustness to various
      possible errors and general applicability to a wider class of pooling
      experiments.

PMID- 9290243
TI  - A Candida albicans genome project: cosmid contigs, physical mapping, and gene
      isolation.
AB  - A new project to map the genome of the pathogenic fungus, Candida albicans, has
      been started. The entire genome was cloned as 5088 cosmids, stored in individual
      microtiter plate wells. DNA was prepared and fingerprinted using restriction
      digestion, fluorescent labeling, and analysis on an ABI sequencer. These data are
      being used to construct contigs of the genome. Simultaneously, a DNA pooling
      system has been set up, suitable for PCR-based isolation of cosmids containing
      any known gene. Ultimately, these approaches will lead to the creation of a
      physically based map of the C. albicans genome, providing the means to localize
      precisely all the genes, act as a substrate for genome sequencing projects, and
      provide probes for future studies of genome rearrangement and comparative
      genomics.

PMID- 9290244
TI  - Mapping chromosome landmarks in the centromere I region of Neurospora crassa.
AB  - Chromosome translocation breakpoints, RFLP heterozygosity in partial chromosome
      duplications, and RFLP-marked crossover events have been used as chromosomal
      landmarks to find the position and orientation of cloned regions flanking
      centromere I of Neurospora crassa. Determination of physical:genetic ratios in
      genomic regions flanking the loci mei-3, un-2, and his-2 supports previous
      evidence indicating that recombinational activity is lower in regions flanking
      centromere I than in the general N. crassa genome. The homogeneous distribution
      of crossover events found in these regions suggests that there is not a gradient
      of crossover inhibition in the vicinity of centromere I. Thus, a largely extended
      centromeric effect and/or a general crossover inhibitory effect operating on
      linkage group I (LGI) could constitute the basis of these abnormal
      physical:genetic ratios. A DNA element containing about 76% A+T was isolated from
      the centromeric end of a cloned region on LGIR. The fragment includes a
      previously undescribed DNA sequence, highly repeated in the Neurospora genome,
      which may correspond to centromeric DNA.

PMID- 9290245
TI  - Genome analysis in Neurospora crassa; cloning of four loci arginine-1 (arg-1),
      methionine-6 (met-6), unknown-7 (un-7), and ribosome production-1 (rip-1) and
      associated chromosome walking.
AB  - We have cloned four Neurospora crassa genes by complementation analysis. Cloned
      genes include the arginine-1 (arg-1), methionine-6 (met-6), unknown-7 (un-7), and
      ribosome production-1 (rip-1) loci. Chromosome walks were initiated in ordered
      cosmid libraries from the cloned loci. A total of about 700 kb of the Neurospora
      genome is covered in these walks.

PMID- 9290246
TI  - Genome analysis on linkage group VI of Neurospora crassa.
AB  - Two chromosome walks covering 420 and 110 kb on the left arm of linkage group VI
      (LGVIL) of Neurospora crassa were purscrooued with the goal of cloning
      carotenogenic loci. Complementation analysis with clones isolated in the 420-kb
      walk allowed identification of the yellow-1 (ylo-1) gene which is essential for
      Neurospora carotenogenesis. We have physically located a second gene, unknown-13
      (un-13), between the cross-pathway control-1, (cpc-1) and ylo-1 loci. Cloning of
      a second potential carotenogenic locus, vivid (vvd), from our walks was attempted
      using screening of Northern blots with radiolabeled DNA fragments from walk
      clones to identify gene transcripts. The radiolabeled DNA fragments were used to
      clone complementary DNA isolates representing an additional four genes in the two
      walks.

PMID- 9290247
TI  - A large-insert (130 kbp) bacterial artificial chromosome library of the rice
      blast fungus Magnaporthe grisea: genome analysis, contig assembly, and gene
      cloning.
AB  - Magnaporthe grisea (Hebert) Barr causes rice blast, one of the most devastating
      diseases of rice (Oryza sativa) worldwide. This fungus is an ideal organism for
      studying a number of aspects of plant-pathogen interactions, including infection
      related morphogenesis, avirulence, and pathogen evolution. To facilitate M.
      grisea genome analysis, physical mapping, and positional cloning, we have
      constructed a bacterial artificial chromosome (BAC) library from the rice
      infecting strain 70-15. A new method was developed for separation of partially
      digested large-molecular-weight DNA fragments that facilitated library
      construction with large inserts. The library contains 9216 clones, with an
      average insert size of 130 kbp (> 25 genome equivalents) stored in 384-well
      microtiter plates that can be double spotted robotically on to a single nylon
      membrane. Several unlinked single-copy DNA probes were used to screen 4608 clones
      in the library and an average of 13 (minimum of 6) overlapping BAC clones was
      found in each case. Hybridization of total genomic DNA to the library and
      analysis of individual clones indicated that approximately 26% of the clones
      contain single-copy DNA. Approximately 35% of BAC clones contained the
      retrotransposon MAGGY. The library was used to identify BAC clones containing a
      adenylate cyclase gene (mac1). In addition, a 550-kbp contig composed of 6 BAC
      clones was constructed that encompassed two adjacent RFLP markers on chromosome
      2. These data show that the BAC library is suitable for genome analysis of M.
      grisea. Copies of colony hybridization membranes are available upon request.

PMID- 9290248
TI  - Expressed sequences from conidial, mycelial, and sexual stages of Neurospora
      crassa.
AB  - In the Neurospora Genome Project at the University of New Mexico, expressed
      sequence tags (ESTs) corresponding to three stages of the life cycle of the
      filamentous fungus Neurospora crassa are being analyzed. The results of a pilot
      project to identify expressed genes and determine their patterns of expression
      are presented. 1,865 partial complementary DNA (cDNA) sequences for 1,409 clones
      were determined using single-pass sequencing. Contig analysis allowed the
      identification of 838 unique ESTs and 156 ESTs present in multiple cDNA clones.
      For about 34% of the sequences, highly or moderately significant matches to
      sequences (of known and unknown function) in the NCBI database were detected.
      Approximately 56% of the ESTs showed no similarity to previously identified
      genes. Among genes with assigned function, about 43.3% were involved in
      metabolism, 32.9% in protein synthesis and 8.4% in RNA synthesis. Fewer were
      involved in defense (6%), cell signalling (3.4%), cell structure (3.4%) and cell
      division (2.6%).

PMID- 9290249
TI  - Multicellular ascomycetous fungal genomes contain more than 8000 genes.
AB  - Fungi comprise a large monophyletic group of uni- and multicellular eukaryotic
      organisms in which many species are of economic or medical importance. Fungal
      genomes are variable in size (13-42 Mb), and multicellular species support true
      spatial and temporal cell-type-specific regulation of gene expression. In a 38.8
      kb Aspergillus nidulans contiguous genomic DNA region, a transposable element and
      12 potential genes were identified, 7 similar to genes in other organisms. This
      observation is consistent with the prediction that multicellular ascomycetous
      fungi harbor 8000-9000 genes in a 36-Mb average genome. Thus, the genomic DNA
      sequence of filamentous fungi will provide substantial amounts of genetic and
      functional information that is not available in yeast, for the human and other
      metazoan minimal gene complement.

PMID- 9290250
TI  - Autonomous plasmid replication in Aspergillus nidulans: AMA1 and MATE elements.
AB  - With few exceptions, in eukaryotic organisms the presence of a chromosomal
      replicator on a circular vector molecule is not sufficient to confer on it the
      ability to persist and replicate extrachromosomally. However, it is possible to
      isolate from genomes of some filamentous fungi DNA fragments which can provide
      extrachromosomal maintenance of plasmids. In Aspergillus nidulans, two functional
      classes of such sequences can be distinguished: effective plasmid replicators
      (e.g., AMA1) and transformation enhancers (e.g., ANS1 or MATEs), which apparently
      are able to initiate aberrant replication, leading to vector rearrangement and
      multimerization and eventually resulting in chromosomal integration. We discuss
      the similarity of these events to DNA amplification in other eukaryotes. A model
      is suggested which accounts for the formation of effective replicating plasmids
      as a result of sequence amplification. The model is based on the observation that
      in some organisms, including A. nidulans and Schizosaccharomyces pombe,
      duplication of an inefficient replicator enhances its efficiency dramatically.
      Some structural traits of transformation enhancers in A. nidulans imply a role
      for topoisomerases in amplification and replication of circular DNA molecules. We
      discuss practical applications of replicative vectors for gene cloning and
      expression studies.

PMID- 9290251
TI  - Evolution of a fungal regulatory gene family: the Zn(II)2Cys6 binuclear cluster
      DNA binding motif.
AB  - The coevolution of DNA binding proteins and their cognate binding sites is
      essential for the maintenance of function. As a result, comparison of DNA binding
      proteins of unknown function in one species with characterized DNA binding
      proteins in another can identify potential targets and functions. The Zn(II)2Cys6
      (or C6 zinc) binuclear cluster DNA binding domain has thus far been identified
      exclusively in fungal proteins, generally transcriptional regulators, and there
      are more than 80 known or predicted proteins which contain this motif, the best
      characterized of which are GAL4, PPR1, LEU3, HAP1, LAC9, and PUT3. Here we review
      all known proteins containing the Zn(II)2Cys6 motif, along with their function,
      DNA binding, dimerization, and zinc(II) coordination properties and DNA binding
      sites. In addition, we have identified all of the Zn(II)2Cys6 motif-containing
      proteins in the sequence databases, including a large number with unknown
      function from the completed Saccharomyces cerevisiae and ongoing
      Schizosaccharomyces pombe genome projects, and examined the phylogenetic
      relationships of all the Zn(II)2Cys6 motifs from these proteins. Based on these
      relationships, we have assigned potential functions to a number of these unknown
      proteins.

PMID- 9290252
TI  - The effect of inorganic and organic supplements on the microbial degradation of
      phenanthrene and pyrene in soils.
AB  - The effects of several bioremediation stimulants, including potential metabolism
      pathway inducers, inorganic/organic nutrients, and surfactants on the metabolism
      of phenanthrene and pyrene, as well as the population dynamics of PAH degrading
      microorganisms was examined in five soils with differing background PAH
      concentrations, exposure histories and physical properties. Most of the
      supplements either had no significant effect or decreased the mineralization of
      [14C]-phenanthrene and [14C]-pyrene in soil slurry microcosms. The effect of a
      particular supplement, however, was often not uniform within or across soils.
      Decreased mineralization of [14C]-phenanthrene and [14C]-pyrene was usually due
      to either preferential use of the supplement as carbon source and/or stimulation
      of non-PAH degrading microorganisms. Many of the supplements increased
      populations of heterotrophic microorganisms, as measured by plate counts, but did
      not increase populations of phenanthrene degrading microorganisms, as measured by
      the [14C]-PAH mineralization MPN analysis or cellular incorporation of [14C]-PAH.
      These results suggest that the PAH degrading community at each site may be unique
      in their response to materials added in an attempt to stimulate PAH degradation.
      The characteristics of the site, including exposure history, soil type, and
      temporal variation may all influence their response.

PMID- 9290253
TI  - Enhancement of ethene removal from waste gas by stimulating nitrification.
AB  - The treatment of poorly water soluble waste gas compounds, such as ethene, is
      associated with low substrate concentration levels in the liquid phase. This low
      concentration level might hamper the optimal development of a microbial
      population. In this respect, the possible benefit of introducing nitrifying
      activity in the heterotrophic removal of ethene at moderate concentrations (<
      1000 ppm) from a waste gas was investigated. Nitrifying activity is known to be
      associated with (i) the production of soluble microbial products, which can act
      as (co-)substrates for heterotrophic micro-organisms and (ii) the co-oxidation of
      ethene. The used reactor configuration was a packed granular activated carbon
      biobed inoculated with the heterotrophic strain Mycobacterium E3. The nitrifying
      activity was introduced by regular submersion in a nitrifying medium prepared
      from (i) compost or (ii) activated sludge. In both cases a clear enhancement of
      the volumetric removal rate of ethene could be observed. When combined with a NH3
      dosage on a daily basis, a gradual increase of the volumetric removal rate of
      ethene could be observed. For a volumetric loading rate of 3 kg ethene-COD.m-3.d
      1, the volumetric removal rate could thus be increased with a factor 1.8, i.e.
      from 0.72 to a level of 1.26 kg ethene-COD.m-3.d-1.

PMID- 9290254
TI  - [Ribavirin in the treatment of bronchiolitis caused by syncytial respiratory
      virus].
AB  - OBJECTIVE: The aim of this study was to evaluate ribavirin therapy for acute
      bronchiolitis caused by viral syncytial respiratory infection. PATIENTS AND
      METHODS: Ninety-seven patients with acute bronchiolitis in which respiratory
      syncytial virus was identified by direct immunofluorescence and admitted to the
      hospital between October 1990 and May 1995 were studied. Data pertaining to age,
      sex, weight, respiratory frequency at admission, respiratory frequency on the
      fourth day, day in which respiratory ausculation was normal, day in which there
      were no thoracic retractions, number of days that the infants needed oxygen,
      duration of hospital stay, and whether or not they were treated with ribavirin
      were collected retrospectively. RESULTS: At admission there were no statistically
      significant differences in patients treated or not with ribavirin or in age, sex
      or weight, but the respiratory frequency was higher in those patients treated
      with ribavirin than in those who were not. The number of days of oxygen therapy
      was statistically different between these groups, with infants treated with
      ribavirin requiring oxygen for 2.7 days and the nontreated group requiring 1.7
      days. However, we think that this difference is not clinically relevant.
      CONCLUSIONS: We did not find any difference of clinical relevance between
      patients treated or not with ribavirin.

PMID- 9290255
TI  - Human genetics: past, present, and future, with special reference to major trends
      in Japan.

PMID- 9290256
TI  - Mucopolysaccharidosis IVA: a novel splice acceptor site mutation in intron 4 of
      the N-acetylgalactosamine-6-sulfate sulfatase gene in an Afghanistan girl with
      classical Morquio disease.
AB  - We report here a novel splice site mutation in intron 4 of the gene for N
      acetylgalactosamine-6-sulfate sulfatase (GALNS) in an Afghanistan girl with
      severe mucopolysaccharidosis IVA (classical Morquio disease). Direct sequencing
      revealed a homozygous G to A transition in the conserved splice acceptor site in
      intron 4 (cagG-->caaG: designated IVS 4(-I) G-->A) which eliminates 144
      nucleotides of exon 5 in her GALNS transcript and introduces an immediate
      premature termination codon (at Trp 141 of exon 4). The IVS 4(-1) G-->A has not
      been seen in other populations and this is the first report of the molecular
      basis of classical Morquio disease in an Afghanistan patient.

PMID- 9290257
TI  - The growth hormone receptor gene mutation of a Japanese patient with Laron
      syndrome.
AB  - Deletions and point mutations of the growth hormone (GH) receptor gene (GHR) have
      been identified in patients with Laron syndrome. We report the first detection of
      the GHR mutation among Japanese patients with Laron syndrome. Using the Japanese
      female patient's genomic DNA as a template, all exons and flanking portions of
      introns of GHR were amplified by polymerase chain reaction (PCR). Sequencing of
      the PCR products showed that the patient was homozygous for a G to A substitution
      at the first position of intron 4. This substitution was same as that detected in
      a Spanish patient and a north European patient. The base change occurred at the
      5' splice consensus sequence of intron 4, resulting in the abolition of a BanI
      restriction site. Since this substitution was not detected by a BanI restriction
      analysis in 85 control individuals, it is more likely a disease-related splice
      mutation than a polymorphism. The mutation in our patient was predicted to
      destroy the original 5' splice site of intron 4 of GHR and to produce a new
      cryptic splice site, leading to abnormal mRNA processing and a lack of GH binding
      activity of GH-binding protein (GHBP).

PMID- 9290259
TI  - Assignment of the human gene for KBF2/RBP-Jk to chromosome 9p12-13 and 9q13 by
      fluorescence in situ hybridization.
AB  - The transcription factor KBF2 has been characterized as a factor that binds to
      the NFkB site of mouse major histocompatibility complex (MHC) class I genes and
      its amino acid sequence has been shwn to be identical to those of members of the
      recombination signal-sequence binding protein (RBP-Jk) family. Previous studies
      by Amakawa et al. (Genomics 17, 306-315, 1993) demonstrated that the functional
      gene is localized at human chromosome 3q25. However, in the present study we
      showed by in situ hybridization with the functional KBF2/RBPJk cosmid clone that
      the gene is localized at 9p12-13 and 9q13, namely, at the same loci as
      pseudogenes that were reported previously (Zhang et al, Jpn J Human Genet 39, 391
      401, 1994).

PMID- 9290258
TI  - Distribution of ABO genotypes and allele frequencies in a Korean population.
AB  - The genotypes of the ABO blood group system were investigated in Korean living in
      Kangwon-Do area by PCR-RFLP analysis of the seven polymorphic nucleotide
      positions 261, 467, 526, 646, 703, 796 and 803 of the cDNA from A1 transferase.
      In 253 unrelated Korean individuals, 15 genotypes were found and the allele
      frequencies of A(Pro), A(Leu), B, O(T) and O(A) were 0.022, 0.209, 0.209, 0.360
      and 0.200, respectively, with no deviation from Hardy-Weinberg expectations (chi
      2 = 2.145, d.f. = 6, 0.90 < p < 0.95). As for the distribution of allele
      frequencies, a significant difference was noticed between the Korean and a
      Japanese (chi 2 = 30.87, d.f. = 4, p < 0.001) and a German (chi 2 = 127.76, d.f.
      = 4, p < 0.001) populations.

PMID- 9290260
TI  - Structure and organization of the human TRKA gene encoding a high affinity
      receptor for nerve growth factor.
AB  - Nerve growth factor (NGF) induces neurite outgrowth and promotes survival of
      embryonic sensory and sympathetic neurons. TRKA, a receptor tyrosine kinase
      cloned from a human colon cancer was later found to be expressed in the nervous
      system and phosphorylated in response to NGF. Somatic rearrangement(s) of the
      TRKA gene (also designated NTRK1) are responsible for formation of some
      oncogenes. Genetic defects in TRKA are responsible for a human disorder,
      congenital insensitivity to pain with anhidrosis (CIPA). We report here isolation
      and characterization of the TRKA gene which spans at least 23 kb and is split
      into 17 exons. Exon sizes range from 18 to 394 bp and intron sizes range from 170
      bp to at least 3.3 kb. Sizes and boundaries of the exons were determined, and all
      the splice donor and acceptor sites conformed to the GT/AG rule. Approximately
      1.2 kb of the 5'-flanking regions was sequenced, and putative regulatory elements
      were identified. These results will be useful for studies on the developmental
      and biological regulation of the TRKA gene and for further characterization of
      mutations in CIPA patients as well as elucidation of mechanisms responsible for
      rearrangement(s) observed in human tumors.

PMID- 9290261
TI  - Polymorphism of extracellular superoxide dismutase (EC-SOD) gene: relation to the
      mutation responsible for high EC-SOD level in serum.
AB  - Extracellular superoxide dismutase (EC-SOD) with amino acid substitution R213G
      generated by the nucleotide substitution 760C-->G in the heparin binding domain
      is responsible for the high EC-SOD level in serum. We identified the two DNA
      polymorphic sites in the coding region of EC-SOD gene related to the 760C-->G and
      determined the allele frequencies. The polymorphism were A and G at nucleotide
      position (nt.) 241 and C and T at nt. 280 near the N-terminal. The haplotype
      frequencies in Japanese were 241A280C: 0.45, 241G280T: 0.37, and 241G280C: 0.18.
      The haplotype of 241A280T did not exist. The mutation 760C-->G must occur on the
      allele having the haplotype of 241G280T.

PMID- 9290262
TI  - Analysis of the first intron of TNFB gene by NcoI RFLP in Koreans.
AB  - The tumor necrosis factor B (TNFB) gene is closely liked with tumor necrosis
      factor A (TNFA) gene between the HLA-B and C2 genes on chromosome 6p21.3. Several
      genetic variabilities at the human TNFB loci have been identified, which are the
      NcoI restriction fragment length polymorphism (RFLP) in the first intron, amino
      acid substitution at codon 26 of exon 3 and EcoRI RFLP in untranslated exon 4.
      The NcoI RFLP of TNFB gene gives two allelic fragments of 238/259 bp and 497 bp,
      corresponding to TNFB*1 and TNFB*2 alleles, respectively. To investigate the
      frequency of NcoI RFLP in the first intron of TNFB in Koreans and to compare to
      that of other ethnic population, genomic DNAs were extracted from leukocytes of
      305 unrelated healthy Koreans and amplified the first intron of TNFB gene by PCR.
      The phenotype frequencies of NcoI RFLP such as TNFB* 1/TNFB*1, TNFB*1/TNFB*2 and
      TNFB*2/TNFB*2 were 8.6% (n = 26), 45.2% (n = 138) and 46.2% (n = 141),
      respectively. The estimated allele frequencies for TNFB*1 and TNFB*2 were 0.3115
      and 0.6885, respectively. The observed and expected frequencies were in good
      agreement with the Hardy-Weinberg's equilibrium. The heterozygosity revealed
      45.2% and the allele frequencies of NcoI RFLP of TNFB in Koreans were observed
      comparatively similar to those of other ethnic groups.

PMID- 9290263
TI  - ITIH1*Q0iwate, a null allele of inter-alpha-trypsin inhibitor H1 caused by
      deletion/frameshift mutation.
AB  - The molecular characterization of the first example of null allele in the inter
      alpha-trypsin inhibitor H1 (ITIH1) system, ITIH1*Q0iwate, encountered as apparent
      inverse homozygosity of ITIH1 phenotypes between mother and child in a paternity
      case, is described. Single-strand conformation polymorphism analysis and
      subsequent sequencing showed that deletion of a single nucleotide in the codon
      for Lys87 results in a frameshift causing a terminator codon downstream of the
      deletion. This leads to premature termination of ITIH1 protein translation at
      amino acid 128, resulting in a truncated protein.

PMID- 9290264
TI  - G-->A transition at nucleotide 2110 in the human platelet glycoprotein (GP) IX
      gene resulting in Ala139(ACC)-->Thr(GCC) substitution.

PMID- 9290265
TI  - Soluble tumor necrosis factor receptor in serum of patients with arthritis.
AB  - Tumor necrosis factor (TNF) induces the production of two forms of soluble
      receptor (p55 and p75) that are present in human serum at concentrations that
      increase greatly in inflammatory rheumatic disease, as well as varying among
      healthy individuals. The purpose of this study was to evaluate the usefulness of
      soluble TNF receptors in distinguishing different forms of arthritis. Serum from
      patients with gout, rheumatoid arthritis, and osteoarthritis, and normal control
      subjects was analyzed for p55, p75, and TNF-alpha by enzyme-linked immunosorbent
      assay. Patients with gout had the highest level of soluble TNF receptor p55,
      while there was no significant difference in the level of this receptor between
      rheumatoid arthritis patients and controls. Both rheumatoid arthritis and gout
      patients had higher soluble TNF receptor p75 levels than osteoarthritis patients
      and control subjects, but there was no difference in the p75 level between
      rheumatoid arthritis and gout patients. Osteoarthritis patients had higher levels
      of p55 and lower levels of p75 than control subjects. The level of TNF-alpha in
      rheumatoid arthritis patients was higher than in osteoarthritis patients, gout
      patients, and control subjects. Determination of soluble TNF receptor levels,
      especially p55, might enable differentiation of rheumatoid arthritis from
      osteoarthritis and gout. The level of p75 cannot be utilized to differentiate
      rheumatoid arthritis and gout, in contrast to the results of previous
      investigations.

PMID- 9290267
TI  - Three-dimensional magnetic resonance cholangiopancreatography for evaluation of
      obstructive jaundice.
AB  - The purpose of this study was to assess the diagnostic value of magnetic
      resonance cholangiopancreatography (MRCP) in studying the anatomy, sites, and
      causes of obstructive jaundice. From September 1994 to May 1996 three-dimensional
      MRCP was performed on 31 patients with abdominal pain and obstructive jaundice
      with a fast spin-echo T2-weighted pulse sequence. The images were reconstructed
      using maximal intensity projection, AVERAGE and SURFACE algorithm processing
      techniques at a graphics workstation. All the reconstructed images were compared
      with those obtained using conventional cholangiographic techniques, such as
      endoscopic retrograde cholangiopancreatography, percutaneous transhepatic
      cholangiography and drainage, and intraoperative cholangiography. The patients'
      diagnoses included choledochal cyst (13), cholangiocarcinoma (five),
      choledocholithiasis (four), pancreatic head carcinoma (three), rhabdomyosarcoma
      (one), papillary Vater carcinoma (one), recurrent gastric carcinoma (one),
      ascaris (one), and biliary atresia (two). Extrahepatic biliary dilatation was
      present in all 13 patients with choledochal cyst; the pancreatic ducts and their
      entrance level to the common bile duct were observed in eight of these patients.
      The level of obstruction in patients with cholangiocarcinoma was well documented
      but the biliary tract of one patient with biliary atresia was not identified by
      MRCP. In one patient with biliary rhabdomyosarcoma, MRCP clearly delineated the
      extrabiliary extension of the tumor. In a patient with ascaris in the common bile
      duct an increase in signal intensity inside the digestive tract of the worm
      denoted fluid in its gut. Lithiasis was shown in all of the four patients with
      choledocholithiasis. Thus, MRCP is a useful tool in the assessment of biliary
      tract obstruction and its causes, and is a valuable addition to ultrasonography.

PMID- 9290266
TI  - Heparin-binding epidermal growth factor-like growth factor and transforming
      growth factor-alpha in human non-small cell lung cancers.
AB  - Transforming growth factor-alpha (TGF-alpha), a member of the epidermal growth
      factor (EGF) family that binds to the EGF receptor (EGFR), is thought to function
      in an autocrine manner in non-small cell lung cancers (NSCLC). Heparin-binding
      EGF-like growth factor (HB-EGF), a novel member of the EGF family, also binds to
      EGFR. To compare the expression of HB-EGF, TGF-alpha and EGFR genes in NSCLC and
      normal lung tissue, we measured the levels of messenger RNA (mRNA) for these
      genes in human NSCLC and normal lung tissues by Northern hybridization, reverse
      transcription-polymerase chain reaction (RT-PCR), and in situ hybridization. A
      total of eight specimens (paired tumor tissue and normal lung tissue) were
      harvested from four patients who underwent resection of primary resectable NSCLC.
      HB-EGF was not expressed in either tumor tissue or normal lung tissue, while EGFR
      and TGF-alpha were expressed in all samples. TGF-alpha was overexpressed in all
      tumor tissue samples by several hundred-fold, while the expression of EGFR was
      not significantly different in tumor tissue and normal lung tissue. There was no
      correlation between the expression of TGF-alpha and EGFR. In situ hybridization
      showed that TGF-alpha mRNA was localized mainly in the cancer cells of tumor
      tissues and in the macrophages of alveoli in normal lung tissue. Our results
      showed that HB-EGF plays no role in the growth of NSCLC, and that there was no
      significant overexpression of EGFR in tumor tissue. TGF-alpha may play a major
      role in the growth of NSCLC. This supports a new direction in rational NSCLC
      treatment.

PMID- 9290269
TI  - Clozapine dosages and plasma drug concentrations.
AB  - Steady-state plasma concentrations of clozapine and its metabolites,
      desmethylclozapine and clozapine-N-oxide, were measured in 162 Taiwanese patients
      with refractory schizophrenia. The daily doses of clozapine ranged from 100 to
      900 mg, with a mean value of 379.5 +/- 142.2 mg. A dosage of 400 mg/day or lower
      was used for most patients (n = 131, 81%). Plasma concentrations of clozapine and
      its two major metabolites were measured using high performance liquid
      chromatography with ultraviolet detection. The mean plasma clozapine
      concentration was 566.9 +/- 398.8 ng/mL. The plasma concentrations of
      desmethylclozapine and clozapine-N-oxide were 46% and 16% of the concentration of
      the parent drug, respectively. We used an approximate rule that each 100 mg/day
      dose results in about 150 ng/mL plasma clozapine. This value is about 30% to 50%
      higher than that reported in Caucasians. The suggested therapeutic plasma
      clozapine concentration range of 300 to 700 ng/mL can be achieved with a dose
      range of 200 to 500 mg/day in most Taiwanese patients. Dose-dependent plasma
      clozapine concentrations were found. The interpatient variation was up to 12-fold
      in patients receiving the same dose, eg, 400 mg/day (n = 62). In four of these
      patients, the plasma drug concentrations were very high (1,446 +/- 114 ng/mL).
      The application of therapeutic drug monitoring in clozapine-treated patients with
      refractory schizophrenia is important, not only in dose adjustment, prediction of
      severe side effects such as seizures, and exploration of drug interactions, but
      also in the effective use of this expensive drug.

PMID- 9290268
TI  - Proton magnetic resonance spectroscopy in patients with complex partial seizures.
AB  - We prospectively studied eight patients with complex partial seizures, using
      single-voxel proton magnetic resonance spectroscopy (MRS). Control data from 12
      healthy volunteers were obtained with the same MRS protocol. The ratios between
      the peak areas of N-acetylaspartate, creatine and phosphocreatine (Cr), and
      choline-containing compounds (Cho) were analyzed. The results showed
      statistically significant lower N-acetylaspartate:Cr, N-acetylaspartate:Cho, and
      N-acetylaspartate: Cho + Cr ratios, and a higher Cho:Cr ratio in the mesial
      temporal lobes of the patient group than in healthy controls. Because N
      acetylaspartate is located in the neurons and Cho and Cr in the glial cells,
      these observations represent the underlying neuronal loss and reactive
      astrocytosis in the epileptogenic foci. MRS can detect abnormal metabolic changes
      in most complex partial seizure patients with normal electroencephalography and
      magnetic resonance images. MRS can also identify bitemporal abnormalities which
      are a common feature in patients with complex partial seizures. Proton MRS could
      not confirm the specific location of seizure foci. Further investigation with
      quantitative spectral analysis and correlation with surgical outcome is needed to
      improve the contribution of MRS to the diagnosis and localization of seizure
      foci.

PMID- 9290270
TI  - Cutaneous microcirculation of diabetic foot: combined isolated cold stress
      testing and laser Doppler flowmetry study.
AB  - We evaluated the peripheral microvascular response to an isolated cold stress
      test in patients with diabetes of various severities. We studied four groups:
      diabetics without neuropathy (group A: six patients), diabetics with peripheral
      motosensory neuropathy (group B: 12 patients), diabetics with peripheral vascular
      disease (group C: eight patients), and healthy controls (group D: 16 patients).
      Digital temperatures of all four groups decreased during the 20-minute cooling
      period, though more in the controls, then increased during the 20-minute
      rewarming period with no difference among the groups. The digital temperatures of
      diabetics with and without neuropathy were higher than those of diabetics with
      peripheral vascular disease and controls throughout. Higher mean digital skin
      temperature was also noted in groups A and B throughout. Significant decreases in
      laser Doppler flowmetry value from the last minute of acclimatization to the last
      minute of the cooling session were found in groups A, B, and D. A significant
      increase during rewarming was found only in group A (p = 0.0475). Our study
      showed that increased digital vascular flow was consistent with arteriovenous
      shunting and abnormal vascular control in diabetics with and without neuropathy.
      Diabetic patients with peripheral vascular disease had the lowest value and the
      least fluctuation in laser Doppler flowmetry, but their digital skin temperature
      did not differ significantly from that of the normal subjects.

PMID- 9290271
TI  - A hypertension control program in Yu-Chi, Taiwan: preliminary results.
AB  - The purpose of this study was to evaluate the feasibility and effectiveness of a
      community approach to hypertension control in both high risk and general
      populations in an agricultural district with limited medical and community
      resources. It was conducted in Yu-Chi district of Nan-Tou county in central
      Taiwan from 1993 to 1994. The study included blood pressure screening, follow-up,
      health education, village-based campaigns, and program evaluation after 6 months
      of intervention. Two villages each were randomly assigned to intervention and
      control groups. Intervention comprised visits by trained volunteers to measure
      blood pressure and body weight, and education related to hypertension. All
      residents 40 years of age and older were enrolled. A total of 471 residents from
      the intervention villages and 426 residents from the control villages completed
      the study. Overall, for the intervention and control groups, the knowledge and
      behavior related to hypertension improved significantly 6 months after the
      baseline survey. The improvement was greater in the subgroup of hypertensives in
      the intervention group than in the controls. The educational intervention also
      significantly improved the status of awareness, treatment, and the control of
      hypertension, and reduced blood pressure in the hypertensive subjects. We
      conclude that a hypertension control program that relies solely on limited
      community resources is feasible and effective.

PMID- 9290272
TI  - Nontuberculous mycobacteria isolates: clinical significance and disease spectrum.
AB  - The incidence of diseases caused by nontuberculous mycobacteria (NTM) is
      increasing worldwide. There has been no previous report regarding the clinical
      significance and disease spectrum of these bacteria in Taiwan. From January 1992
      to June 1996, 201 isolates of NTM were recovered from clinical specimens from 143
      patients at National Taiwan University Hospital. We retrospectively studied the
      clinical records and radiographs of these patients. A total of 86 isolates of NTM
      were considered clinically significant; they were cultured from 39 patients with
      soft-tissue infections and/or osteomyelitis (16 patients), isolated pulmonary
      infections (10), keratitis (6), disseminated infections (4), peritonitis,
      enteritis, and conjunctivitis. The most common organisms involved in these
      patients were Mycobacterium fortuitum complex, followed by Mycobacterium avium
      intracellulare. Positive cultures of NTM were derived from respiratory sources
      (sputum, bronchial washing, and pleural effusion) from 111 patients; in 11 the
      isolates were associated with clinically significant disease, in two they were
      persistent colonizers, in 79 the isolates were considered to be contaminants, and
      for the remainder there were insufficient cultures to classify. The organisms
      involved in pulmonary diseases were M. avium-intracellular (4 patients),
      Mycobacterium chelonae (1), Mycobacterium abscessus (1), M. fortuitum (2),
      Mycobacterium gordonae (1), and unidentified scotochromogens (2), M. fortuitum
      complex (55%) was the most common pathogen of keratitis and soft-tissue
      infection. Three of the four cases of disseminated disease were caused by M.
      avium-intracellulare. The only isolate of Mycobacterium kansasii found in this
      study was a contaminant. The strains of clinically significant NTM isolates found
      in our hospital and their disease spectrum differ from those reported in other
      regions of the world.

PMID- 9290273
TI  - Clinical characteristics and antimicrobial susceptibility of invasive group B
      streptococcal infections in nonpregnant adults in Taiwan.
AB  - To understand group B streptococcal infections other than peripartum events in
      adults and to provide a regional antimicrobial therapy guide, we conducted a
      retrospective analysis of invasive diseases caused by group B streptococcus (GBS)
      in 33 nonpregnant adults treated in a medical center in southern Taiwan, from
      January 1993 to July 1994. Antimicrobial susceptibility tests were performed
      using the agar dilution method. The incidence of the disease was 1.6 per 1,000
      nonpregnant adult admissions, and the mean age of patients was 58 years (range 17
      86 years). Primary bacteremia (13) and soft-tissue infections (11) were the most
      common manifestations. Nearly all the patients had underlying disease(s) and/or
      condition(s); the three most common were diabetes mellitus (13), malignancy (5),
      and liver cirrhosis (5). There were eight nosocomial infections and six patients
      died. Of 32 GBS strains tested, 27 were susceptible to penicillin G and the rest
      were intermediately susceptible. All strains were uniformly susceptible to
      cephalothin, cefotaxime, ofloxacin, and vancomycin; two strains were susceptible
      to gentamicin and nearly half were intermediately susceptible. Our findings imply
      a requirement for higher doses of penicillin or combination with an
      aminoglycoside for treatment of GBS infection. First-generation cephalosporins
      may be an alternative for the treatment of GBS infections in Taiwan.

PMID- 9290274
TI  - Uncemented total arthroplasty in old quiescent infection of the hip.
AB  - We reviewed the outcomes of 24 cases (24 patients) of uncemented total hip
      arthroplasty done to treat secondary osteoarthritis due to quiescent previous
      infection. There were 16 men and eight women aged from 24 to 78 years (mean, 50
      yr). Eight patients had proven or probable tuberculous infection and the other 16
      patients had a past history of septic hip. The patients were followed for between
      2.5 and 7 years (mean, 4.5 yr). According to the Harris hip rating system, 18 of
      the patients had excellent or good results. Three patients had a preoperative
      erythrocyte sedimentation rate of 40 mm/h or higher and had a positive bacterial
      culture. Two of these patients developed reinfection. The other 21 patients had a
      preoperative erythrocyte sedimentation rate less than 40 mm/h and no reinfection
      postoperatively. There were five complications other than infection: dislocation
      with ipsilateral femoral shaft fracture, intraoperative femoral fracture, cup
      loosening, periprosthetic osteolysis, and nonunion of the greater trochanter.
      Uncemented total arthroplasty for old quiescent infection of the hip should be
      considered if the preoperative erythrocyte sedimentation rate is normal and a
      course of prophylactic antituberculous therapy is given in patients with an old
      tuberculous hip.

PMID- 9290275
TI  - Cycling injuries among junior high school children in Taiwan.
AB  - We surveyed the injuries sustained by 197 junior high school students (aged 12 to
      15 years) while riding a bicycle within the previous 12 months, together with the
      same number of controls matched according to age and sex. The case sites and
      control sites, selected from routes control subjects would have taken if pursuing
      the same purpose as the case subject at the time of the accident, were also
      investigated. Male students and older students were found to be at higher risk.
      One-third of the injuries occurred while the students were traveling to school.
      Nearly 40% of the accidents happened between 15:00 and 19:00, and 52% occurred
      during the summer months. More than half of the accidents took place near street
      corners. Injuries were mainly (89%) to one of the limbs. Injuries were more
      severe among those with head injuries. None of the injured children wore a helmet
      while cycling. Most injuries (83%) were due to collisions with another vehicle.
      Motorcycles were involved in the collisions most often. When compared with the
      total number of registered vehicles, the proportion of trucks, light commercial
      vans, and taxis involved in the crashes was significantly higher. Drivers of the
      vehicles involved were primarily males, evenly distributed across all age groups.
      The volume of traffic was marginally heavier at case sites, but estimated average
      speeds of vehicles were similar between case and control sites. More obstacles,
      such as illegally parked vehicles and vendors' stalls, were found at case sites.
      In addition to wearing a helmet, other prevention strategies should be
      considered.

PMID- 9290276
TI  - Flat adenoma of the colon: two cases.
AB  - Flat adenoma has been frequently reported to have a higher potential for
      malignant change than other polypoid adenomas. It is an endoscopically visible
      sessile lesion that consists histologically of an adenomatous change of the
      colonic mucosa. Detection, diagnosis, and treatment of flat adenoma has not
      previously been reported in Taiwan. We found such lesions in two patients during
      colonoscopic examinations as patches of discolored and irregular mucosa.
      Histopathologic studies revealed adenomas with mild to moderate dysplasia.
      Patient 1 underwent segmental colectomy; patient 2 underwent an endoscopic strip
      biopsy. Focal malignant changes were noted in patient 1. Both patients received
      close follow-up at the outpatient clinic. No recurrence has been seen in patient
      1. Patient 2 developed an enlarged sessile lesion with a histologic picture
      showing a tubular adenoma without malignancy but refused further surgical
      treatment. This paper outlines the endoscopic and pathologic characteristics of
      flat adenoma in two patients, and should alert physicians to the importance of
      early detection and treatment of this lesion.

PMID- 9290277
TI  - Cardiac angiomyolipoma: radiologic and pathologic correlation.
AB  - Primary tumors of the heart are rare. We report a case of large cardiac
      angiomyolipoma (hamartoma) that presented as a fat-containing tumor mass on
      imaging studies, diagnosed radiographically as teratoma. The patient was admitted
      through the emergency room at Tainan Municipal Hospital because of severe
      dyspnea. A chest radiograph revealed marked widening of the mediastinum.
      Echocardiography and computed tomographic scanning of the thorax showed a mass of
      mixed density with calcification. A teratoma with intrapericardial invasion was
      suspected. Sternotomy disclosed a large intrapericardial lobulated mass (34 x 30
      x 12 cm, 3,150 g) arising from the right atrium, with severe adhesion to the
      origin of the inferior vena cava. Histopathologic examination demonstrated an
      angiomyolipoma of the heart. To our knowledge, this is the largest cardiac
      angiomyolipoma reported. We report this case to emphasize that a differential
      diagnosis of angiomyolipoma must be included in a patient with a fat-containing
      cardiac tumor.

PMID- 9290278
TI  - Right aortic arch with mirror-image branching and coarctation of the aorta.
AB  - We report a case of right aortic arch with mirror-image branching and coarctation
      of the aorta and left ductus arteriosus in a 6-year-old boy. He was referred to
      Chang Gung Children's Hospital with suspected left ventricular failure. Physical
      examination revealed hypertension and a pulse discrepancy between the upper and
      lower extremities. Echocardiography and magnetic resonance imaging revealed a
      right aortic arch, a long segmental aortic coarctation, and a patent ductus
      arteriosus. In addition, mirror-image branching of the brachiocephalic vessels
      was found. The coarctation was resected and the ductus arteriosus was ligated.
      The postoperative recovery was uneventful and the blood pressure returned to
      normal. He remained normotensive and had no symptoms of heart failure within the
      2 years of follow-up.

PMID- 9290279
TI  - Topographic disorientation: two cases.
AB  - Topographic disorientation is very rare, and usually occurs as a result of a
      right occipitotemporal lesion. The substrates accounting for these symptoms are
      thought to be the right parahippocampal and lingual gyri. I report two cases of
      topographic disorientation. Patient 1, a 58-year-old male taxi driver, suddenly
      lost his way while driving home. At presentation he could neither describe nor
      draw a route from one place to another. This patient gradually regained his
      topographic orientation over the course of 3 months. Patient 2, a 58-year-old
      male farmer, suffered a headache and visual hallucinations, and subsequently lost
      his bearings. He could describe and draw a map of a route in detail, although the
      streets that he traveled daily appeared strange to him. The topographic
      disorientation of patient 2 had changed little 3 years after the onset. Both
      patients had left homonymous hemianopia, but no prosopagnosia, constructional
      apraxia, unilateral spatial neglect, or other cortical dysfunction. Brain
      computed tomography revealed an infarct of the right posterior cerebral artery,
      involving the cuneus and lingual gyri, in both patients. The lesion was located
      more dorsally in patient 1, involving part of the right parietal lobe, and more
      ventrally in patient 2, involving the right parahippocampal gyrus, which might
      account for the discrepancy between their topographic orientation and the
      clinical course.

PMID- 9290280
TI  - Agrobacterium radiobacter bacteremia in a patient with chronic obstructive
      pulmonary disease.
AB  - Agrobacterium radiobacter is a gram-negative bacillus, which is recognized as an
      emerging opportunistic human pathogen. To our knowledge, there have been only 25
      cases of A. radiobacter bacteremia reported. In most of these, A. radiobacter was
      associated with long-term indwelling plastic central venous catheters. We
      describe a 78-year-old man who had a history of chronic obstructive pulmonary
      disease with long-term use of a corticosteroid. He was admitted to the China
      Medical College Hospital with pneumonia caused by Serratia marcescens. His
      general condition gradually improved after initiation of appropriate treatment.
      Unfortunately, he developed A. radiobacter bacteremia while hospitalized in the
      medical intensive care unit. With the onset of this infection, the patient had a
      high fever, leukocytosis, raised C-reactive protein level, and positive blood
      cultures for A. radiobacter. A central venous catheter-related infection was
      suspected because of redness and localized tenderness at the catheter site. The
      patient gradually recovered after removal of the catheter and appropriate
      antimicrobial treatment with latamoxef 1.5 g intravenously every 8 hours for 10
      days.

PMID- 9290281
TI  - Improving neonatal care in a developing country.

PMID- 9290282
TI  - Helping children relax during magnetic resonance imaging.

PMID- 9290283
TI  - Group B streptococcus and pregnancy: update and recommendations.

PMID- 9290284
TI  - Neonatal group B streptococcal disease.

PMID- 9290285
TI  - Limiting legal liability in the NICU.

PMID- 9290287
TI  - Liability for unlicensed assistive personnel, Part I.

PMID- 9290286
TI  - Congenital diaphragmatic hernia: what happens after discharge?

PMID- 9290289
TI  - The Fort Bragg Sniper Attack and Mental Health Response.

PMID- 9290288
TI  - Tuberculosis treatment of women and children.

PMID- 9290290
TI  - Estrogenic hormones and dental implant therapy: the effects of estrogen and
      progesterone levels on osseointegration of dental implants.
AB  - Successful rehabilitation of female service members suffering traumatic injuries
      to the maxillofacial region is both a physiological and a psychological issue. A
      clinical evaluation to determine if an association exists between sex hormone
      levels and dental implant success was undertaken. Endosseous dental implants were
      placed in three patient groups: (1) male controls, (2) females with high
      estrogen, and (3) females with low estrogen. Female groupings were based on
      ovulation cycles. Serum estrogen (ng/dl), serum progesterone [ng/dl], and serum
      interleukin-6 (pg/ml) were determined at time of implant placement. Pre- and
      postsurgical photographs and vinyl-polysiloxane impressions were taken to
      evaluate crestal alveolar bone loss. Upon data analysis, the authors concluded
      that the balance of alveolar osseous wound healing was not influenced by temporal
      fluctuations in the ovulatory cycle.

PMID- 9290291
TI  - Factors influencing perceived need for dental care by active duty U.S. military
      personnel.
AB  - This study explores factors that influence perceived need for dental care among
      active duty U.S. military personnel. The data were collected on a prestratified
      random sample of 12,950 (76% response rate) service members between April 1994
      and January 1995. Participants received a comprehensive oral examination from a
      dentist and answered queries concerning perceived need on self-administered
      questionnaires. Using bivariate and logistic regression analyses, we examined the
      association between demographic and clinical measures and perceived need for
      dental care. Bivariate results show that half of all U.S. military personnel
      perceive a need for dental care, with statistically significant differences
      across race, rank, education, branch of service, dental health class, and dental
      utilization. Logistic regression results show that the likelihood of perceived
      need is influenced by age, race, rank, branch of service, dental disease, dental
      health class, and dental utilization. Extensive dental decay is the strongest
      predictor of perceived need in this population.

PMID- 9290292
TI  - Provider workforce model for regional TRICARE networks.
AB  - A model is presented that can estimate the total number and specialty mix of
      health care providers needed to serve a defined population. Military commanders
      in charge of TRICARE regions, known as "lead agents," can use this model to
      estimate the provider workforce composition needed to serve their area. Physician
      staffing patterns front managed-care organizations help define the provider-to
      patient proportions on which this model is based. Data needed to perform the
      model's computations are derived from the regional enrolled beneficiary
      population and the number of active duty providers. As a result, the model
      provides an estimate of the number and type of civilian providers that need to be
      contracted to adequately serve the regional military network.

PMID- 9290293
TI  - A form of human intercourse?
AB  - The philosophical basis of military medicine needs to be understood fully before
      progress can be made in doctrine, organization, training, and resourcing. During
      a time of increased resource constraint and radical restructuring of the
      military, an opportunity arises for a fundamental reexamination of the nature and
      philosophy of military medicine. In order to be effective in the role, a military
      physician needs to fully understand the obligations of the two professions that
      he or she straddles. The military physician needs to be fully conversant with the
      profession of arms as well as being a medical professional. The obligations of
      the two may occasionally be divergent, but the physician has an important role to
      play in reconciling them. This action may act synergistically and produce a
      maximally effective military system.

PMID- 9290294
TI  - Army family practice: does our training meet our needs?
AB  - OBJECTIVES: (1) To determine the perceived adequacy of residency training for
      current practice by Army family physicians; (2) to ascertain if differences exist
      by residency setting: medical center, medical activity, or civilian. METHODS:
      Surveys were mailed to the 334 family physicians in the Army in 1993. Training in
      various subject areas was rated as inadequate, adequate, or overly prepared.
      RESULTS: More than 75% of respondents felt prepared in 76% of general medical
      subjects (GM) but in only 39% of family medicine subjects (FM). There were no
      practice management subjects in which more than 75% felt adequately prepared.
      There were no differences in perceptions of GM or FM training between military-
      and civilian-trained respondents. CONCLUSIONS: Army and civilian residencies
      prepare family physicians for the medical aspects of practice. Early training in
      management subjects could be enhanced. Civilian and Army programs could improve
      training in family medicine subjects.

PMID- 9290295
TI  - Combat psychiatry: from history to theory.
AB  - Effective combat psychiatry requires specific knowledge of social psychiatry's
      ethics and morals and is incompatible with commonly used psychiatries. Its
      demonstrated usefulness requires that the psychiatrist be assigned with combat
      forces, where his membership is with them and not with hospitals. This lesson,
      learned in the Italian campaign of World War II and demonstrated as effective in
      the Korean War, remains in constant jeopardy of being forgotten because the
      required ethics and morals are so readily rejected by civilian and individual
      oriented psychiatrists untaught about special psychiatry. The history of the
      conflict between ideologies that took place in World War II and threatened the
      war effort is presented here. It is suggested that such dangerous conflicts
      between fundamental and strongly held civilian and military convictions remain
      poorly understood.

PMID- 9290296
TI  - Warm water immersion foot: still a threat to the soldier.
AB  - We report a significant incidence of warm water immersion foot (WWIF) in a light
      infantry battalion during a field exercise. Four hundred soldiers belonging to
      this battalion were surveyed to determine the prevalence of the WWIF syndrome.
      One hundred forty-nine soldiers surveyed developed the WWIF syndrome. The
      affected soldiers had a wide range of disability, ranging from mild discomfort to
      the inability to ambulate. All soldiers had full recovery within 2 weeks of the
      injuries. Although the syndrome is self-limited, the loss of these soldiers from
      combat critically impaired the battalion in its mission. We present this report
      as a reminder that effective preventive measures should be taken prior to field
      exercises and deployments.

PMID- 9290297
TI  - Detection of interleukin-6 and interleukin-2 in serum of rhesus monkeys exposed
      to a nonlethal dose of staphylococcal enterotoxin B.
AB  - The immune response to a nonlethal dose of aerosolized staphylococcal enterotoxin
      B (SEB) was studied in nonhuman primates to define the potential human host
      response to a nonlethal exposure of SEB on the battlefield. Serum levels of the
      cytokines interleukin 2 (IL-2) and interleukin 6 (IL-6) increased significantly
      (p < 0.01) in six juvenile rhesus monkeys 4 hours after receiving a nonlethal,
      inhaled dose of SEB. The mean (+/-SD) peak serum levels of IL-2 and IL-6 were 63
      +/- 39 units/ml and 514 +/- 234 pg/ml, respectively, post-SEB treatment. Tumor
      necrosis factor, known to be associated with SEB-mediated lethal toxic shock, was
      undetectable in all samples. gamma-Interferon concentrations were also elevated,
      but not significantly [p < 0.089]. Hence, elevated levels of IL-2 and IL-6 might
      be used as a serological marker for a nonlethal, incapacitating exposure to SEB.

PMID- 9290298
TI  - Pharmacological management of post-traumatic stress disorder: clinical summary of
      a five-year retrospective study, 1990-1995.
AB  - Beginning in 1990, the Department of Psychiatry. Tripler Army Medical Center
      developed a formal treatment program for post-traumatic stress disorder (PTSD).
      Between 1990 and 1996, 632 patients, the vast majority of whom suffered from
      combat-related PTSD, were treated. Historically, many PTSD patients were treated
      with benzodiazepines, often in high dosages. The risks attendant to
      benzodiazepine management of PTSD, coupled with poor clinical outcome, prompted
      the staff to explore treatment alternatives. This paper describes the role of
      pharmacotherapy in the management of PTSD. The medications described in this
      paper have other primary uses in clinical practice (e.g., hypertension, insomnia,
      seizure control, depression, and anxiety). Medications were selected for use
      based on the putative modes of action and the degree of symptom relief. The
      therapeutic rationale was to decrease hyperarousal and sleep disturbance to
      permit the patients to engage in other psychotherapeutic efforts.

PMID- 9290299
TI  - The maternity care practice of Navy family practice residency graduates while on
      active duty.
AB  - BACKGROUND AND OBJECTIVES: Military family practice residency programs produce a
      high percentage of graduates who provide maternity care. This study will define
      the scope of maternity care practice for one military family practice residency
      program's graduates while they were serving on active duty in the U.S. Navy.
      METHODS: Two hundred eight surviving graduates of the family practice residency
      at Naval Hospital, Jacksonville, Florida, from 1971 to 1995 were surveyed by mail
      regarding their maternity care practice while on active duty. One hundred eighty
      one (87%) responded to the survey, and the data were analyzed with descriptive
      statistics. FINDINGS: The vast majority of these Navy family practice residency
      graduates provided prenatal care (88.4%) and routine vaginal delivery services
      (85.1%) while on active duty. The majority repaired third- and fourth-degree
      perineal lacerations and performed vacuum- or forceps-assisted vaginal delivery.
      Additionally, a significant minority provided more advanced maternity care
      services such as dilation and curettage, tubal ligation, and cesarean section.
      The overwhelming majority (97%) of these graduates felt that their residency
      education had adequately prepared them to provide these maternity care services
      while on active duty. CONCLUSIONS: During the past 25 years, Navy residency
      trained family physicians provided a wide range of maternity care services while
      on active duty and felt that their Navy residency training program had prepared
      them well to meet this responsibility.

PMID- 9290300
TI  - The effects of prolonged passive heat exposure and basic military training on
      thermoregulatory and cardiovascular responses in recruits from a tropical
      country.
AB  - This study investigates the effects of long-term passive heat exposure and a 16
      week basic military training program on heat acclimatization. Thirty recruits
      were tested on the zero (T1), 2nd (T2), 6th (T3), and 16th (T4) weeks of the
      basic military training program. The trials involved 1 hour of marching on a
      treadmill at 5.5 km h-1, with a 5% gradient. The subjects wore their camouflage
      uniforms during the trials, with simulated combat loads. The trials were
      conducted in a climatic chamber programmed at 32 degrees C, 60% relative
      humidity, 900 Wm-2 of simulated solar radiation, and wind speed of 3 m s-1. There
      was no fluid replacement during the trials. Because only 9 subjects attended all
      the trials, the results presented are based on these subjects. No significant
      difference was found in mean skin temperature in all the four trials. Tympanic
      temperature was significantly reduced (p < 0.05) only at 20 minutes. Pairwise
      analysis was significant (p < 0.05) only between T1 (37.18 +/- 0.38 degrees C)
      and T4 (36.48 +/- 0.53 degrees C). Average body temperature was significantly
      different only at 10 and 60 minutes (p < 0.05). A significant pairwise difference
      (p < 0.05) was found only between T1 (36.61 +/- 0.33 degrees C) and T4 (36.07 +/-
      0.46 degrees C) in 10 minutes. No pairwise difference was found at 60 minutes.
      Mean heart rate (HR) was significantly reduced during the 16 weeks at 10, 20, and
      30 minutes. Mean HR at 10 minutes was reduced from 152.11 +/- 14.18 beats min-1
      in T1 to 130.78 +/- 10.43 beats min-1 in T4 (p < 0.001). Mean HR at 20 and 30
      minutes was reduced from 156.11 +/- 17.74 beats min-1 (T1) to 137.25 +/- 11.42
      beats min-1 (T4) (p < 0.001), and from 157.14 +/- 15.77 beats min-1 (T1) to
      146.11 +/- 12.64 beats min-1 (T4) (p < 0.05). There was no significant difference
      in sweat loss and mean sweat rate during the 16 weeks. This study concluded that
      long-term passive heat exposure was effective at inducing heat acclimatization in
      terms of tympanic temperature, average body temperature, mean skin temperature,
      sweat loss, and mean sweat rate, but not in terms of HR. Physical training was
      still necessary to induce further adaptation in HR. The limiting factor to task
      completion during the trials was physical fitness rather than beat fitness.

PMID- 9290301
TI  - Case managed mental health care in the San Antonio catchment area: the crisis
      intervention unit.
AB  - Through the use of government nursing case management, this crisis-focused
      inpatient psychiatric program provided cost-effective and therapeutically
      directed services to Civilian Health and Medical Program for the Uniformed
      Services (CHAMPUS)-eligible beneficiaries in the San Antonio catchment area.
      Using managed care principles and a continuum-based case management model, these
      services were provided in local contracted civilian facilities. This acute care
      mental health program directly saved Brooke Army Medical Center 1.1 million
      mental health dollars and saved 7.7 million CHAMPUS dollars in total cost
      avoidance. Program costs were minimal, resulting in a 557% return on investment.
      A joint Army/Air Force endeavor, the program was originally administered by the
      Coordinated Care Division, Brooke Army Medical Center as a CHAMPUS recapture
      initiative. Currently under TRICARE management, the program continues intact as a
      managed care mental health service alternative.

PMID- 9290302
TI  - Rickettsialpox-like illness in a traveler.
AB  - A patient presented after a trip to South Africa with a febrile illness and rash
      that was consistent with either rickettsialpox or mild boutonneuse fever. The
      clinical, laboratory, and geographic overlap of these diseases makes
      differentiation difficult in certain situations. Several different rickettsial
      infections may cause an eschar and a rash that may be papulovesicular. From a
      clinical perspective, distinguishing these diseases is not critically important
      as long as therapy with tetracycline is implemented. More precise identification
      of the etiologic agent could be required in certain military situations because
      the preventive measures employed for some of these diseases may be significantly
      different.

PMID- 9290303
TI  - Preoperative gadolinium-enhanced magnetic resonance pulmonary venography in an
      adolescent with atrial septal defect.
AB  - The conventional preoperative evaluation of congenital heart disease in the adult
      using only echocardiography and cardiac catheterization is frequently limited. We
      report a case in which newer magnetic resonance imaging with gadolinium
      angiographic techniques proved helpful by conclusively documenting normal
      pulmonary venous return in a patient with secundum [corrected] atrial septal
      defect. This evaluation obviated the need for referral to a more specialized
      tertiary-care center for congenital heart disease and dramatized the value of an
      interdisciplinary approach to the adult patient with newly diagnosed congenital
      heart disease.

PMID- 9290304
TI  - Measurement of health-related quality of life of patients receiving conservative
      treatment for limb lymphoedema using the Nottingham Health Profile.
AB  - There is increasing interest in the health-related quality of life (HRQOL) of
      patients with chronic oedema. Studies in this area have tended to be exploratory
      and little work has examined the potential for HRQOL as a treatment outcome
      indicator in this context. This study aimed to ascertain whether or not
      conservative treatment for lymphoedema results in a measurable change in HRQOL,
      using the Nottingham Health Profile Part 1 (NHP-1) as the study instrument.
      Thirty-four patients participated. The patients received a range of conservative
      treatments. The participants completed the NHP-1 prior to treatment and 4 weeks
      after completion of the initial treatment phase. The overall post-treatment NHP-1
      scores were significantly lower than the overall pre-treatment scores (z = 3.1
      and p < 0.01), indicating an improvement in the HRQOL. The greatest change in a
      single dimension was in physical mobility (z = 2.3 and p < 0.05). The change in
      limb volume was not associated with a change in any NHP-1 subscale. A significant
      correlation was found between an improvement in skin condition and an improvement
      in scores on the 'pain' subscale (r = 0.53 and P < 0.01). It is concluded that
      the NHP-1 was useful in the assessment of the 'physical' domains of HRQOL in this
      context, but was less useful with regard to psychological and emotional domains.

PMID- 9290305
TI  - Measurement of health-related quality of life in men with prostate cancer: the
      CaPSURE database.
AB  - This paper reviews the reliability and validity of an instrument for assessing
      health-related quality of life (HRQOL) in CaPSURE (Cancer of the Prostate
      Strategic Urologic Research Endeavor), an observational database of men with
      biopsy-confirmed prostate cancer. The questionnaire includes the RAND 36 item
      Health Survey 1.0, the UCLA Prostate Cancer Index and items measuring self-esteem
      and the impact of prostate cancer in general and on the family. The reliability
      and validity of this instrument are reported for a group of 2,382 men enrolled in
      CaPSURE. Individuals complete HRQOL questionnaires at enrollment and quarterly
      thereafter. The subscales of the instrument resulted in a high internal
      consistency reliability across all subscales (range = 0.75-0.94). The test-retest
      reliability was good with the exception of the comparative health item
      (intraclass correlation coefficient (ICC) = 0.55). The concurrent validity data
      included moderately strong associations with subscales of similar concepts and
      the ability to distinguish between patients who are known to be different--newly
      diagnosed (within 6 months) and patients diagnosed and treated an average of 3
      years ago. Overall, this instrument demonstrated good reliability and validity
      and supported the need for incorporating HRQOL as a component of outcomes
      assessment in the management of patients with prostate cancer.

PMID- 9290306
TI  - Causal indicators in quality of life research.
AB  - Quality of Life (QOL) questionnaires contain two different types of items. Some
      items, such as assessments of symptoms of disease, may be called causal
      indicators because the occurrence of these symptoms can cause a change in QOL. A
      severe state of even a single symptom may suffice to cause impairment of QOL,
      although a poor QOL need not necessarily imply that a patient suffers from all
      the symptoms. Other items, for example anxiety and depression, can be regarded as
      effect indicators which reflect the level of QOL. These indicators usually have a
      more uniform relationship with QOL, and therefore a patient with poor QOL is
      likely to have low scores on all effect indicators. In extreme cases it may seem
      intuitively obvious which items are causal and which are effect indicators, but
      often it is less clear. We propose a model which includes these two types of
      indicators and show that they behave in markedly different ways. Formal
      quantitative methods are developed for distinguishing them. We also discuss the
      impact of this distinction upon instrument validation and the design and analysis
      of summary subscales.

PMID- 9290309
TI  - [Recent advances in medical virology. 1. Introduction].

PMID- 9290307
TI  - A new self-completion outcome measure for diabetes: is it responsive to change?
AB  - Self-completion instruments assessing subjective health are increasingly being
      used to measure patient outcome. However, there is very little evidence as yet of
      existing instruments' responsiveness to change. This paper describes a study to
      evaluate the responsiveness to change of a self-completion instrument for the
      measurement of clinical outcome in patients with diabetes. A prospective follow
      up study of 48 patients with non-insulin-dependent diabetes commencing insulin
      therapy was carried out, with assessments at baseline (i.e. pre-intervention), 6
      weeks and 3 months post-intervention. The outcome measures used were the changes
      in scores on the self-completion instrument for symptom level, physical function,
      energy, depression, psychological distress and barriers to activity, HbA1c, non
      fasting serum cholesterol and the body mass index (BMI). There were significant
      improvements in HbA1c and non-fasting serum cholesterol and worsening of the BMI,
      as expected. The self-completion instrument detected significant improvements in
      patient-reported symptoms within 6 weeks of the intervention (p < 0.01) and in
      energy levels (p < 0.05). There is evidence from this study of the self
      completion instrument's ability to respond to change and it has potential for use
      in evaluative studies.

PMID- 9290308
TI  - Regional diastolic function in hypertrophic cardiomyopathy: a tissue Doppler
      echocardiographic study.
AB  - BACKGROUND: Tissue Doppler echocardiography (TDE) is a recent ultrasonic
      technique. One of its potential clinical uses is the assessment of regional
      diastolic function. OBJECTIVES: To compare left ventricular global diastolic
      function with interventricular septum regional diastolic function in patients
      with hypertrophic cardiomyopathy with different levels of global diastolic
      dysfunction. METHODOLOGY: 10 normal subjects (group 1), eight hypertrophic
      cardiomyopathy patients with abnormal relaxation (group 2) and 12 patients with
      hypertrophic cardiomyopathy with restrictive pattern (group 3) on the mitral
      inflow profile (pulsed wave Doppler) were studied. Each patient performed an M
      mode color; TDE of the basal septum in the four chamber view. Velocities during
      the rapid filling phase (RF), and during atrial contraction (AC) were measured
      and RF/AC ratio calculated in each patient. RESULTS: While in normal subjects
      (group 1) the RF/AC ratio was always higher than 1, in patients with hypertrophic
      cardiomyopathy patients with different levels of global diastolic dysfunction
      (groups 2 and 3), the RF/AC ratio was always lower than 1 (velocities during
      atrial contraction always higher than during rapid filling), despite the level of
      global diastolic dysfunction. CONCLUSIONS: A ratio between myocardial velocities
      during the rapid filling phase and during atrial contraction lower than one
      (RF/AC < 1) is a tissue Doppler echocardiography index of regional diastolic
      dysfunction, independently of the severity of global diastolic dysfunction.

PMID- 9290310
TI  - [Genetic divergence of measles virus and clinical significance].

PMID- 9290312
TI  - [Preparing for the next pandemic influenza: vaccine and antivirals].

PMID- 9290311
TI  - [Polio vaccine and polio eradication initiative--progress of polio eradication in
      China].

PMID- 9290313
TI  - [Possible association of Borna disease virus with human diseases].

PMID- 9290314
TI  - [Human herpesvirus 6 and 7 infections].

PMID- 9290315
TI  - [Human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus].

PMID- 9290317
TI  - [Induction and suppression of apoptosis by adenovirus genes].

PMID- 9290316
TI  - [Induction of apoptosis by influenza virus infection].

PMID- 9290318
TI  - [Regulation of apoptosis by the latent infection membrane protein 1 and the early
      protein BHRF1].

PMID- 9290319
TI  - [The role of env in HIV-mediated apoptosis].

PMID- 9290320
TI  - Is group selection a factor modulating the virulence of RNA viruses?
AB  - RNA viruses consist of populations of extremely high genetic heterogeneity called
      quasispecies. Based on theoretical considerations, it has been suggested that the
      unit of selection in such complex genetic populations is not the single viral
      particle but a set of genetically related particles which form the quasispecies.
      In the present study we carried out a set of experiments with the vesicular
      stomatitis virus (VSV) dealing with the evolution of life-history characters
      under selection acting at two factors either in the same or in opposite
      directions. The two factors at which selective pressure is applied are the
      individual and the group. We show evidence that group selection modulates the
      virulence of VSV populations, in opposition to an unlimited increase in virulence
      by competitive optimization promoted by individual selection. The results are of
      relevance for understanding the evolution of parasite virulence.

PMID- 9290321
TI  - Role of transposable elements in age-related genomic instability.
AB  - Genetic instability is associated with aging in many species. One of the
      initiating factors for genetic instability is the movement of transposable
      elements (TEs), which occur in all prokaryotic and eukaryotic organisms. The
      hypothesis that TEs could be involved in the aging process is discussed and the
      correlation between aging and activity of TEs is analysed in a variety of
      biological systems.

PMID- 9290322
TI  - Characterization of natural populations of Drosophila melanogaster with regard to
      the hobo system: a new hypothesis on the invasion.
AB  - Until now, with regard to the hobo system of hybrid dysgenesis, natural
      populations of Drosophila melanogaster have been investigated using only two
      criteria: at the molecular level, the presence or absence of XhoI fragments 2.6
      kb long or smaller; and/or at the genetic level, the ability to induce gonadal
      dysgenesis sterility in crosses A (females of an E reference strain crossed with
      males under test) and A* (females under test crossed with males of an H reference
      strain). Recently, analyses of laboratory strains using these criteria as well as
      the mobilization of two reporter genes, the male recombination and the number of
      'TPE' repeats in the S region, revealed a lack of correlation between the
      different dysgenic parameters themselves, and also between these parameters and
      the molecular characteristics of the strains. Thirteen current strains derived
      from world populations were therefore investigated with regard to all these
      dysgenic traits, to determine discriminating criteria providing a robust method
      of classifying natural populations and deducing the dynamics of hobo elements in
      these populations. We show, as in laboratory strains, a lack of correlation
      between the parameters studied. Therefore, the significance of each of them as
      well as the nature of hobo hybrid dysgenesis are discussed, to propose an
      analysis method of the hobo system applicable to natural populations. According
      to the geographical distribution of hobo activities in world populations and to
      the variable polymorphism of the number of 'TPE' repeats, we propose a new
      scenario for the invasion of D. melanogaster by hobo elements.

PMID- 9290323
TI  - The effect of cryopreservation on the lethal mutation rate in Drosophila
      melanogaster.
AB  - Although cryopreservation is routinely used for the storage of a range of
      biological organisms, few studies have been conducted to determine whether
      cryopreservation increases the frequency of mutation. A procedure for the
      cryopreservation of Drosophila melanogaster embryos has recently been developed.
      Cryopreservation of D. melanogaster is of special interest to geneticists and
      evolutionary biologists because it would make it possible to assay control and
      experimental populations simultaneously during long-term studies. Before
      cryopreserved embryos can be used for such studies, it is first necessary to show
      that cryopreservation is not mutagenic. We tested for mutagenic effects or
      cryopreservation in D. melanogaster embryos with an X-linked, recessive lethal
      assay. The mutation rates of cryopreserved and control flies were not
      significantly different. We can be 95% certain that cryopreservation does not
      increase mutation by a factor greater than 2.39. This is the first quantitative
      estimate of the mutagenic effect of cryopreservation on the germ line of a
      metazoan. The results are reassuring when considering the genetic impact of
      cryopreservation on mammalian gametes and embryos.

PMID- 9290324
TI  - Effects of leptin administration on long-term selected fat mice.
AB  - To assess the role of genetic changes in sensitivity to leptin hormone in
      contributing to responses to long-term selection for fatness, leptin was
      administered to a long-term fat selected (F) and a control line (C) of mice.
      These lines differ almost three fold in their percentage of fat (fat%) at about
      15 weeks of age. Treated (T) animals received twice-daily intraperitoneal
      injections of 5mg/kg leptin from 91 to 105 days of age; untreated (U) animals
      received equivolume injections of phosphate-buffered saline. Treated compared
      with untreated animals in both lines had significantly (P < 0.05) lower mean body
      weight, food intake and fatness at the end of test (fat%: CT 3%, CU 7.4%, FT
      14.9%, FU 21.1%). The differences in response between the lines [(CT-CU)-(FT-FU)]
      were all non-significant (P > 0.05), however. There was a very wide range of
      fatness (estimated from dry matter content) among FT animals (3-29%), much higher
      than in FU (15-31%), CT (0.7-6.4%) and CU (2-15%) animals. While sensitivity to
      leptin remains in the fat line, response appears to vary among animals at the
      dose level used.

PMID- 9290325
TI  - The use of selection experiments for detecting quantitative trait loci.
AB  - Gene frequency changes following selection may reveal the existence of gene
      effects on the trait selected. Loci for the selected quantitative trait (SQTL)
      may thus be detected. Additionally, one can estimate the average effect (alpha)
      of a marker allele associated with an SQTL from the allele frequency change
      (delta q) due to selection of given intensity (i). In a sample of unrelated
      individuals, it is optimal to select the upper and lower 27% for generating delta
      q in order to estimate alpha. For a given number of individuals genotyped, this
      estimator is 0.25i2 times more efficient than the classical estimator of alpha,
      based on the regression of the trait on the genotype at the marker locus. The
      method is extended to selection criteria using information from relatives,
      showing that combined selection considerably increases the efficiency of
      estimation for traits of low heritability. The method has been applied to the
      detection of SQTL in a selection experiment in which the trait selected was pig
      litter size averaged over the first four parities, with i = 3. Results for four
      genes are provided, one of which yielded a highly significant effect. The
      conditions required for valid application of the method are discussed, including
      selection experiments over several generations. Additional advantages of the
      method can be anticipated from determining gene frequencies on pooled samples of
      blood or DNA.

PMID- 9290326
TI  - A new chromosomal polymorphism by duplication of a heterochromatic region in
      cattle.

PMID- 9290328
TI  - The consumption bomb.
AB  - The explosion of the population bomb has long been predicted to cause massive
      famine in overpopulated countries. Rising consumption, even in a time of
      decreasing population growth rates, now threatens adverse global health effects
      more severe than localised famines. The world faces potential ecological
      entrapment. This has two dimensions: planetary eco-impoverisation and planetary
      eco-pathology. Eco-impoverisation, the depletion of natural capital, arises as
      the limit of the global human carrying capacity approaches. Eco-pathology, the
      disruption of ecological support systems, arises because of the way the biosphere
      has been modified by human activity and is caused particularly by unsustainable
      consumption for human purposes. Despite encroaching ecological entrapment, the
      dominant economic paradigm claims record levels of growth; a paradox that needs
      recognition. Reasons for denial of the gravity of ecological entrapment are
      discussed. Ways are suggested to defuse the consumption bomb and avert ecological
      entrapment.

PMID- 9290327
TI  - The radiological hazards of plutonium.
AB  - About 1,500 tonnes of plutonium, 1,200 tonnes civilian, are now in world
      stockpiles, of which 200 tonnes have been separated from spent fuel in
      reprocessing plants. This will rise to 300 tonnes by the year 2000. Such reactor
      grade plutonium contains a higher proportion of isotopes other than Pu-239, which
      progressively increases with longer burn-up. These isotopes have an increased
      risk of causing cancer, particularly if inhaled. Possible cancer rates from
      scattering of such plutonium in a city centre (e.g. by terrorist activity) are
      considered, and the implications of these calculations for the wisdom of
      continued reprocessing of spent nuclear reactor fuel are discussed.

PMID- 9290329
TI  - Armed conflicts, health and health services in Africa. An epidemiological
      framework of reference.
AB  - Because of war, between the 1980s and early '90s Africa suffered about 5 million
      excess deaths and economic losses estimated at US $13 billion per year. In 1995,
      war was directly or indirectly affecting 550 million people in 35 countries.
      Besides violent deaths, injuries and disabilities, displacements of population
      increase the risk for acute respiratory infections, diarrhoeas, epidemics and
      parasitic disease. The risk for malnutrition and deficiencies is made worse by
      the loss of means of production, of food stocks, of commerce and by banditism.
      Military operations target water plants and health facilities as means of
      deliberately hurting civilians. Economic crisis curtails the budgets of the
      social sectors and, together with social distress, undermines national
      capacities. The delivery of health care is hampered right when hazards and
      vulnerabilities increase, with general greater risk of illness and death. With
      the cessation of hostilities, the need for curative and preventative health
      activities increases and is a matter of emergency, as equitable access to
      services is important for peace. Repatriation of refugees, demobilization of
      soldiers and demining require special health activities. War leaves behind new
      hazards and vulnerabilities such as landmines, wide availability of weapons,
      artificial concentrations of population, loss of national capacities and
      psychological disorders. All this interacts tragically with Africa's wider
      epidemiological realities of poverty, food insecurity, proneness to natural
      disasters and endemic diseases.

PMID- 9290330
TI  - [365 days of danger of allergy by powdered latex gloves].

PMID- 9290331
TI  - [The taking of organs is permitted after brain death].

PMID- 9290332
TI  - [A new information system for the transfer of patients in need of care: smooth
      continuing care which centers on the patient's needs must be assured].

PMID- 9290334
TI  - [Sexuality--a tabu in nursing: proximity to the patient can be frightening].

PMID- 9290333
TI  - [Care of patients with tracheostomies: their psychological condition needs
      special attention].

PMID- 9290336
TI  - [Finland--nursing science from a different perspective: there is light and shade
      in the far north too].

PMID- 9290335
TI  - [The introduction of nursing standards: the project will fail without the
      acceptance of the coworkers].

PMID- 9290337
TI  - [The role of organization in the hospital of the future: responsibilities will
      have to be redistributed].

PMID- 9290338
TI  - [Operating room nurse turns into a screen writer: the nutty hospital becomes a
      reality].

PMID- 9290339
TI  - [Falls and drowning accidents: are errors in primary care the cause?].

PMID- 9290340
TI  - [Stress for the patient and the nurse. Stress experience and control by nurses.
      Care of cancer patients is getting to me...].

PMID- 9290342
TI  - [Fatigue and exhaustion syndrome].

PMID- 9290341
TI  - [Stress and its control in cancer patients. Loss of appetite and cachexia--nausea
      and vomiting].

PMID- 9290344
TI  - [Nursing transfer at the bedside].

PMID- 9290343
TI  - [Development and movement in oncologic nursing. Resource-oriented care--change of
      thought in oncologic nursing].

PMID- 9290345
TI  - [Importance of nursing research in nursing practice].

PMID- 9290346
TI  - [Preserving the proven principles in the health care system].

PMID- 9290347
TI  - [Figures of the German Hospital Society prove the increase in productivity of
      hospitals and nurses: nursing is a paid service--and not a cost factor of the
      hospital].

PMID- 9290349
TI  - [Health care and its economics have to be disentangled].

PMID- 9290350
TI  - [External services are increasing].

PMID- 9290352
TI  - [Selection of the legal form of a hospital. Its effects are also concerning
      care].

PMID- 9290351
TI  - [Psoriasis has many manifestations].

PMID- 9290353
TI  - [Biography-oriented pedagogy with long-term hospitalized patients. After some
      years the institution is regarded as home].

PMID- 9290354
TI  - [Motivation of coworkers--an important guidance measure. The nursing
      administration can influence the attitude of nursing personnel].

PMID- 9290355
TI  - [Nursing education courses in Germany. 11. In Hamburg education is based on the
      total professional field].

PMID- 9290356
TI  - [Mobile rehabilitation is recognized: a gap in geriatric care has been closed].

PMID- 9290357
TI  - [Family work in the hospital--a challenge for professional nurses].

PMID- 9290358
TI  - Classifying posterior vitreous detachment: a new way to look at the invisible.

PMID- 9290359
TI  - Investigating signs and symptoms in dry eyed patients.

PMID- 9290360
TI  - Organ culture: the method of choice for preservation of human donor corneas.

PMID- 9290361
TI  - Variations of posterior vitreous detachment.
AB  - AIMS: To identify variations in posterior vitreous detachment (PVD) and establish
      a clinical classification system for PVD. METHODS: 400 consecutive eyes were
      examined using biomicroscopy and vitreous photography and classified the PVD
      variations-complete PVD with collapse, complete PVD without collapse, partial PVD
      with thickened posterior vitreous cortex (TPVC), or partial PVD without TPVC.
      RESULTS: In each PVD type, the most frequently seen ocular pathologies were as
      follows: in complete PVD with collapse (186 eyes), age related changes without
      vitreoretinal diseases (77 eyes, 41.4%) and high myopia (55 eyes, 29.6%); in
      complete PVD without collapse (39 eyes), uveitis (23 eyes, 59.0%) and central
      retinal vein occlusions (8 eyes, 20.5%); in partial PVD with TPVC (64 eyes),
      proliferative diabetic retinopathy (30 eyes, 46.9%); and inpartial PVD without
      TPVC (111 eyes), age related changes without vitreoretinal diseases (62 eyes,
      55.9%). This PVD categorisation was significantly associated with the prevalence
      of each vitreoretinal disease (p < 0.0001, chi 2 test on contingency table).
      CONCLUSIONS: PVD variations can be classified into four types, which is
      clinically useful because each type corresponds well to specific vitreoretinal
      changes.

PMID- 9290362
TI  - Effectiveness of hyaluronan on corneal epithelial barrier function in dry eye.
AB  - AIMS/BACKGROUND: The aim of this study was to assess quantitatively the
      effectiveness of hyaluronan on corneal disruption in patients with dry eye.
      Corneal epithelial barrier function was evaluated by measuring fluorescein
      permeability using a slit-lamp fluorophotometer. METHODS: 11 patients with dry
      eye were assigned to this study. Hyaluronan ophthalmic solution (0.1% hyaluronic
      acid) was instilled five times a day to the right eye, in addition to the usual
      artificial tear solutions. The left eye received only the artificial tear
      solutions. Corneal barrier function was evaluated on the pretreatment day, and at
      2 and 4 weeks after treatment. Fluorophotometry was used to measure fluorescein
      uptake at the central and lower corneal portions. RESULTS: Two weeks after
      treatment, hyaluronan treated right corneas showed significant corneal epithelial
      barrier improvement in the lower portion, compared with the pretreatment day (p <
      0.025). Four weeks after treatment, the treated corneas showed significant
      improvement in the central corneal portion (p < 0.025) and improvement in the
      lower portion, compared with the pretreatment day. The untreated left corneas, on
      the other hand showed no improvement during the course of the study. CONCLUSION:
      This study suggests that hyaluronan is effective in the treatment of corneal
      epithelial disruption in dry eye.

PMID- 9290364
TI  - Holmium laser thermokeratoplasty for the reversal of hyperopia after myopic
      photorefractive keratectomy.
AB  - BACKGROUND: Overcorrection following myopic photorefractive keratectomy, with a
      target of emmetropia, leaving a spherical equivalent of more than 1.0 D of
      hyperopia is of the order of 1%. This study analyses the efficacy, safety, and 1
      year stability of outcome of laser thermokeratoplasty (LTK) carried out on eyes
      with persistent symptomatic hyperopia following photorefractive keratectomy (PRK)
      for myopia. METHOD: 11 consecutive eyes in 11 patients underwent LTK using the
      Technomed Holmium 25, contact holmium:YAG laser system. The mean spherical
      equivalent before LTK was +2.06 D (SD 1.02 D, range +1.00 D to +4.75 D) based on
      a non-cycloplegic refraction. Between four and 16 burns were used per eye,
      depending on the error to be corrected. RESULTS: The mean spherical equivalent
      was +0.511 D (SD 0.551) at 1 year. Ten of the 11 eyes were seeing 6/12 or
      greater, unaided (91%) and nine were within 1.0 D of the target sphere equivalent
      (82%). Recovery of unaided acuity occurred during the first week in four cases
      and the first month in the rest. One eye lost greater than one line of best
      corrected vision (9%), going from 6/5 to 6/7.5 and one gained a line (9%), 6/12
      to 6/7.5. No complications occurred during the follow up period. CONCLUSIONS: In
      this study of a small number of eyes with hyperopia induced by PRK, LTK appears
      safe, predictable, and stable for low errors followed for 1 year.

PMID- 9290363
TI  - Corneal infiltration after recurrent corneal epithelial erosion.
AB  - AIMS: To describe the clinical features of patients with a history of recurrent
      corneal epithelial erosion who develop acute corneal infiltration. METHODS: The
      records were reviewed of patients who had previously been examined and treated
      for recurrent corneal epithelial erosion and who presented again with signs
      suggestive of a microbial keratitis. RESULTS: 11 patients were described; one
      patient presented with similar signs on two occasions. There was typically a
      paracentral epithelial defect > 2 mm in diameter with an associated stromal
      infiltrate and an intense anterior uveitis. Three patients had a hypopyon, and
      four developed a subepithelial ring infiltrate. Samples were taken for microscopy
      and bacterial culture, with a positive isolate from two of 12 episodes (16%).
      Treatment with topical antibiotics and topical corticosteroid resulted in rapid
      re-epithelialisation and a reduction of inflammation. There was good visual
      outcome for all eyes, with a recurrence or symptoms of epithelial erosion in only
      one eye after a mean follow up period of 18 months. CONCLUSIONS: Corneal
      infiltrates are an uncommon complication of recurrent corneal epithelial erosion.
      Despite the intensity of the infiltration the majority are culture negative using
      established techniques. There is typically rapid resolution and a good visual
      outcome, with a tendency for the episode to mark the end of further symptoms of
      epithelial erosion.

PMID- 9290365
TI  - Relation between postoperative blood-aqueous barrier damage and LOCS III cataract
      gradings following routine phacoemulsification surgery.
AB  - AIM: To examine the relation between cataract density, the phacoemulsification
      energy required for its removal, and blood-aqueous barrier (BAB) damage on the
      first day after surgery. METHODS: A prospective study recruiting patients with
      normal eyes apart from senile cataract. Preoperatively, visual acuity, anterior
      chamber laser flare, and cell values were measured using the Kowa laser flare
      meter, and the LOCS III grading of the cataract defined. The patients all
      underwent standardised phacoemulsification surgery through a superior scleral
      tunnel incision, with confirmed in the bag placement of a one piece PMMA IOL; all
      surgical complications were excluded. The phaco power delivered was recorded as
      the cumulative delivered energy, CDE. On day 1 visual acuity and laser flare and
      cell readings were taken. RESULTS: 101 patients were recruited and all completed
      the protocol. Older patients had a higher preoperative flare value (p = 0.003);
      preoperative cell values were significantly related to nuclear opacity (p =
      0.021) and colour (p = 0.011). Postoperative flare was related to preoperative
      flare (p = 0.001) and nuclear colour (p = 0.038). CDE was related to nuclear
      colour (p = 0.031) and opacity (p = 0.022), but not to aqueous flare.
      CONCLUSIONS: Damage to BAB after routine phacoemulsification surgery is predicted
      by the preoperative flare values and the density of the cataract nucleus. The
      amount of phacoemulsification energy required to remove a cataractous lens is
      related to the density of the cataract but affects postoperative flare to a
      minimal degree. Other factors such as surgical technique are probably more
      important. Laser photometry is a useful tool for objectively assessing surgical
      technique.

PMID- 9290366
TI  - Conventional routine clinical review may not be necessary after uncomplicated
      phacoemulsification.
AB  - AIM: To determine the clinical intervention rate during routine review after
      uncomplicated phacoemulsification. METHODS: A review of case notes in 651
      consecutive cases of uncomplicated phacoemulsification from 1994 (< or = 5.5 mm
      self sealing wound) was performed. The intervention rate at scheduled routine
      review visits and at unscheduled visits to the eye casualty service in the first
      120 postoperative days was recorded. Interventions were defined as departures
      from predetermined postoperative care protocols. RESULTS: Clinical interventions
      were reported in 2.8% (95% confidence interval 1.5 to 4.1%) of (n = 1652) routine
      follow up visits. Many of these interventions were avoidable or trivial; 90% of
      patients had no postoperative intervention at any visit. 7.3% of patients made
      unscheduled visits to the emergency service. The intervention rate in this group
      was 50% (35.9 to 64.1%). CONCLUSIONS: The intervention rate in routine clinical
      review after uncomplicated modern cataract surgery is low. Alternatives to
      conventional postoperative review, including shared care with non
      ophthalmologists and improved perioperative patient education with an open
      channel for self referral, should be evaluated.

PMID- 9290367
TI  - Combined PRK and PTK in myopic patients with recurrent corneal erosion.
AB  - AIM: To study the results of combined photorefractive keratectomy (PRK) and
      phototherapeutic keratectomy (PTK) in myopic patients with recalcitrant recurrent
      corneal erosion. METHODS: PRK was performed in 16 eyes with the Visx 20/20
      excimer laser at a central 6.0 mm zone, following total epithelial scraping.
      Subsequently, confluent 3.0 mm zones of PTK were ablated at a depth of 6.0
      microns, surrounding the zone of PRK. The follow up period ranged from 26 to 42
      months. RESULTS: Complete alleviation of symptoms was demonstrated and there was
      no recurrence of corneal erosion. Visual acuity (VA) improved slowly following
      treatment, with a final uncorrected VA ranging between 6/9 and 6/12. A final
      myopic spherical equivalent < or = -1.0 D was found in 14 out of 16 eyes.
      CONCLUSIONS: A combination of PRK and PTK is effective in the alleviation of
      symptoms and prevention of recurrences of corneal erosion. It is suggested that
      recalcitrant recurrent corneal erosion is a diffuse disease, although it often
      manifests as a local problem, and therefore extensive excimer laser ablation is
      required to prevent recurrence and to alleviate symptoms completely.

PMID- 9290368
TI  - Trabeculectomy with intraoperative sponge 5-fluorouracil in Afro-Caribbeans.
AB  - AIM: To study the efficacy and safety of intraoperative 5-fluorouracil (5-FU) in
      Afro-Caribbean patients. METHODS: The results of trabeculectomy in 18 eyes of 18
      Afro-Caribbean patients in whom a sponge soaked in 25 mg/ml solution of 5-FU was
      applied between Tenon's capsule and sclera for 5 minutes before excision of the
      trabecula were compared with 16 eyes of 16 Afro-Caribbean patients matched for
      age, quantity, and duration of preoperative medications, who underwent
      trabeculectomy without 5-FU. RESULTS: The mean postoperative intraocular pressure
      (IOP) at 1 month was 15.6 (SD 6.1) mm Hg in the 5-FU group and 18.0 (5.2) mm Hg
      in the control group (p = 0.15). There was no significant difference in the IOP
      at 6, 12, 15, 18, and 24 months in the two groups. Success rate at 18 months
      defined as an IOP less than or equal to 21 mm Hg with no adjunctive medication
      was 56% in the 5-FU group and 55% in the control group. No major complications
      were noted in either group. CONCLUSION: Intraoperative sponge 5-FU alone is safe
      but does not appear to decrease the risk of failure of trabeculectomy in Afro
      Caribbeans.

PMID- 9290369
TI  - Incidence and survival of retinoblastoma in The Netherlands: a register based
      study 1862-1995.
AB  - AIM: The aim of this study was to determine the (time trends in) incidence and
      survival of hereditary (familial and sporadic) and non-hereditary retinoblastoma
      for male and female patients born in the Netherlands between 1862 and 1995.
      METHOD: The national retinoblastoma register was updated and now consists of 955
      patients. The missing dates of death were obtained from the municipal registers
      and the Central Bureau of Genealogy in The Hague. Mortality was compared with the
      Dutch vital statistics. RESULTS: From 1862 to 1995 no significant differences in
      incidence for retinoblastoma were found in the hereditary subgroups. Further, no
      significant differences between males and females were found, both overall and in
      the hereditary subgroups. The average incidence of retinoblastoma increased until
      1944, probably due to incompleteness of the register, and stabilised after 1945
      (1 per 17000 live births). From 1900 to 1995 the standardised mortality ratio
      increased for hereditary retinoblastoma patients from 2.9 to 9.0 and decreased
      for non-hereditary retinoblastoma patients from 1.9 to 1.0. CONCLUSION: Although
      survival for retinoblastoma was significantly better after 1945 than before, in
      comparison with the Dutch population the mortality between 1900 and 1990
      increased for the hereditary and decreased for the non-hereditary retinoblastoma
      patients.

PMID- 9290370
TI  - Does cryotherapy before drainage increase the risk of intraocular haemorrhage and
      affect outcome? A prospective, randomised, controlled study using a needle
      drainage technique and sustained ocular compression.
AB  - AIMS/BACKGROUND: A prospective, randomised, controlled clinical trial was
      conducted to investigate the effect of performing cryotherapy before drainage of
      subretinal fluid (SRF) on the incidence of intraocular haemorrhage (IOH) in the
      management of retinal detachment. METHODS: Eighty eyes of 80 patients with
      rhegmatogenous retinal detachment requiring SRF drainage were recruited. Thirty
      four cases were randomised to receive drainage before cryotherapy (drainage, air
      injection, cryotherapy, and explant = DACE group) while 46 cases had drainage
      after cryotherapy (cryotherapy, drainage, air injection, and explant = CDAE
      group). All cases had trans-scleral drainage of SRF using a 27 gauge hypodermic
      needle combined with prolonged, intraocular hypertension. RESULTS: There was a
      low incidence of IOH associated with drainage in both groups with no
      statistically significant difference between the groups (DACE group = 2.9%; CDAE
      group = 4.3%; p = 0.43). There was no significant difference between the groups
      in the rate of anatomical success with a single operation (DACE group = 82.4%;
      CDAE group = 86.9%; p = 0.38). There was no significant difference between the
      groups in the visual outcome. An improvement of two Snellen lines or more
      occurred in 52.9% of the DACE group and in 56.5% of the CDAE group (p = 0.93).
      CONCLUSION: It was concluded that the surgical sequence of applying cryotherapy
      before drainage of SRF can be safely and effectively performed. The sequences
      CDAE and CDE, when air injection is not required, along with DACE should all be
      part of the surgical repertoire for the management of retinal detachments.

PMID- 9290371
TI  - Scanning laser fundus perimetry before laser photocoagulation of well defined
      choroidal neovascularisation.
AB  - AIM: To assess the centre of fixation before laser photocoagulation of well
      defined juxtafoveal or extrafoveal choroidal neovascularisation (CNV) secondary
      to age related macular degeneration (AMD), and to better predict visual function
      after treatment using scanning laser ophthalmoscope (SLO) fundus perimetry.
      METHODS: 19 consecutive eyes with juxtafoveal or extrafoveal CNV were examined by
      fundus perimetry before and after laser treatment with documentation of the
      fixation point using the SLO. The stability of fixation was defined as standard
      deviation around the mean fixation point. Overlays of fluorescein angiographic
      pictures and fundus perimetry were obtained using image analysis software.
      RESULTS: Fundus perimetry allowed accurate determination of the centre of
      fixation. Overlays demonstrated the precise geographic relation of the
      angiographically detectable foveal margin of the CNV and the centre of fixation.
      Thereby, prediction of the visual outcome with regard to reading ability was
      facilitated. Stability of fixation did not change significantly after treatment.
      CONCLUSIONS: Fundus perimetry using the SLO was helpful in patients who underwent
      laser treatment for juxtafoveal or extrafoveal CNV secondary to AMD and may aid
      the pretreatment counselling of such patients.

PMID- 9290372
TI  - Visual impairment and socioeconomic factors.
AB  - BACKGROUND: Information about socioeconomic factors associated with visual
      impairment can assist in the design of intervention programmes. Such information
      was collected by the Melbourne Visual Impairment Project (Melbourne VIP).
      METHODS: The Melbourne VIP was a population based study of non-institutionalised
      permanent residents in nine suburbs of the Melbourne metropolitan area aged 40
      years of age and older. A standardised eye examination was provided to eligible
      residents which included a structured interview. Variables of interest for this
      analysis were age, sex, country of birth, language spoken at home, education
      level, use of private health insurance, employment status, and living
      arrangements. Visual impairment was defined as a best corrected visual acuity <
      6/18 and/or visual field constriction to within 20 degrees of fixation. RESULTS:
      A total of 3271 (83%) residents participated. Participants ranged in age from 40
      to 98 years; 54% were female. Forty four (1.34%) were classified as visually
      impaired due to visual acuity and/or visual field loss. To evaluate the
      independent association of the significant sociodemographic variables with visual
      impairment, a regression model was constructed that included age, retirement
      status, use of private health insurance, and household arrangement. The results
      showed that age was the significant predictor of visual impairment (OR: 3.19; CI:
      2.29-4.43), with the mean age of people with visual impairment significantly
      older (75.0 years) compared with people without visual impairment (58.2 years) (t
      test = 9.71; p = 0.0001). Of the 44 visually impaired people, 39 (87%) were aged
      60 years of age and older. CONCLUSION: The results indicate that age is the most
      significant factor associated with visual impairment. Of some importance was the
      finding that people with visual impairment were less likely to have private
      health insurance. With the aging of the population, the number of people affected
      by visual impairment will increase significantly. Intervention programmes need to
      be established before the onset of middle age to offset the escalation of visual
      impairment in the older population.

PMID- 9290373
TI  - A clinic based survey of blindness and eye disease in Cambodia.
AB  - AIMS: To survey the spectrum of eye disease presenting to rural eye clinics in
      Cambodia. METHODS: A total of 1381 patients seen consecutively at 13 eye clinics
      were examined and the findings recorded. RESULTS: 231 (16.7%) were bilaterally
      blind (visual acuity < 3/60 in both eyes); 263 (19%) were unilaterally blind, and
      169 (12%) had low vision (visual acuity < 6/18 in the better eye). Cataract was
      the commonest cause of visual loss in all three categories and was responsible
      respectively in 69%, 40%, and 55% of each group. Trachoma was diagnosed in 13% of
      patients. Thirty three of them needed lid surgery for trichiasis. CONCLUSION:
      With the difficult practical and political situation in Cambodia there seems
      little prospect of making substantial inroads into the backlog of avoidable
      blindness in the near future.

PMID- 9290374
TI  - Complications of fascia lata harvesting for ptosis surgery.
AB  - AIMS/BACKGROUND: The aim of this study was to assess the morbidity associated
      with harvesting autogenous fascia lata for brow suspension ptosis surgery.
      METHODS: A retrospective study by postal questionnaire of 24 consecutive
      patients. RESULTS: Early postoperative problems with pain on walking (67%),
      limping (38%), and wound pain (57%) occurred mostly for less than 1 week. The
      final cosmetic appearance of the scar caused minor concern in 38% of patients.
      CONCLUSION: Fascia lata is the preferred material for permanent ptosis correction
      when a brow suspension is required. Most of the patients, following fascia lata
      harvest, experienced some symptoms of leg pain and limping for less than 1 week.
      The only long term problem was the scar. 38% of patients found the final cosmetic
      appearance caused minor concern.

PMID- 9290375
TI  - Effect of mitomycin C on the optic nerve in rabbits.
AB  - AIM: To prevent scarring after surgical optic nerve sheath decompression, it has
      been suggested that treating the area of fenestration with mitomycin C (MMC)
      might be effective. An animal model was used to test whether this toxic substance
      may cause optic neuropathy. METHODS: The optic nerves of 15 rabbits were exposed
      to balanced salt solution (BSS) or mitomycin C (MMC) in a concentration of 0.2 or
      0.5 mg/ml. The unoperated fellow eyes and the eyes that received BSS served as
      controls. Steady state visual evoked potentials (VEPs) at 40, 50, and 60 Hz were
      recorded before and 4 weeks after surgery. The nerves were examined by light and
      electron microscopy after 5 weeks. RESULTS: VEPs in all non-operated eyes and
      eyes treated with BSS before and 4 weeks after surgery demonstrated responses at
      all three stimulus frequencies tested. Eyes operated with MMC had extinguished
      responses for one, two, or all the different temporal frequencies after 4 weeks
      with marked reduction in VEP amplitude. Eyes operated with MMC at a concentration
      of 0.5 mg/ml had significantly more reduced VEP responses than those where MMC
      0.2 mg/ml was used. On histopathological examination, special stains for myelin
      and axons showed normal axons and myelin. On electron microscopy, no distinct
      abnormalities were seen among nerves operated with MMC and controls. CONCLUSION:
      The data from this study suggest that in rabbits, the application of MMC to the
      optic nerve has a dose dependent toxic effect in the short term postsurgical
      follow up period. While a functional alteration could be demonstrated
      reproducibly by steady state VEPs, the extent was not obvious on
      histopathological examination of the nerves.

PMID- 9290376
TI  - Plasminogen in proliferative vitreoretinal disorders.
AB  - OBJECTIVE: Intravitreal fibrin formation is a frequent observation after
      vitrectomy performed for a variety of vitreoretinal disorders including
      proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR),
      and endophthalmitis. Plasminogen activators (PA) have been used for the
      management of this postoperative complication. This approach requires the
      presence of plasminogen, the substrate for PA mediated fibrinolysis, in the
      vitreal cavity. METHODS: Quantification of plasminogen in the vitreous of 60
      patients with PVR, PDR, and macular pucker was performed by streptokinase
      mediated activation using a chromogenic substrate. The presence of immunoreactive
      plasminogen was confirmed by immunoblot analysis of vitreal proteins and
      immunocytochemistry of surgically removed epiretinal membranes. RESULTS:
      Plasminogen levels were dramatically increased in the vitreous of PVR and PDR
      patients compared with macular pucker patients and normal controls. Staining for
      plasminogen in epiretinal membranes was confined to the extracellular matrix.
      Predominant staining of perivascular areas in PDR specimens indicated that
      breakdown of the blood-retinal barrier is an important source of intravitreal
      plasminogen in that condition. CONCLUSION: Plasminogen may play a role in
      traction membrane formation in PVR and PDR. Our biochemical analysis of
      presurgical vitreous indicates that there may be abundant substrate for PA
      mediated fibrinolysis in the vitreous cavity after vitrectomy.

PMID- 9290377
TI  - Human papilloma virus in neoplastic and non-neoplastic conditions of the external
      eye.
AB  - AIM: Human papilloma virus (HPV) types 16 and 18 have been associated with
      neoplastic conditions of the conjuctiva. However, the presence of this virus has
      not been reported in non-neoplastic disorders of the external eye nor has it been
      studied in normal conjunctival tissues. METHODS: Ninety six paraffin embedded
      tissue specimens with neoplastic and non-neoplastic lesions and 19 conjunctiva
      samples free from overt disease were studied for HPV types 16 and 18 positivity
      with the polymerase chain reaction. RESULTS: HPV types 16 and 18 DNA were
      identified in 57% of in situ squamous cell carcinoma, in 55% of invasive squamous
      cell carcinoma, in 20% of climatic droplet keratopathy, in 35% of scarred
      corneas, and in 32% of normal conjunctival tissue obtained during routine
      cataract extractions. CONCLUSION: These findings indicate that HPV types 16 and
      18 are detectable with the polymerase chain reaction not only in epithelial
      neoplasms of the ocular mucous membrane but also in non-neoplastic lesions as
      well as in apparently healthy conjunctiva.

PMID- 9290379
TI  - Unsuspected infections crystalline keratopathy masquerading as corneal graft
      rejection.

PMID- 9290380
TI  - Angle closure glaucoma as a presenting sign of Vogt-Koyanagi-Harada syndrome.

PMID- 9290381
TI  - Schwartz-Matsuo syndrome: atypical presentation as acute open angle glaucoma.

PMID- 9290382
TI  - Capsular bag distension syndrome.

PMID- 9290378
TI  - Use of isolated ocular arteries in vitro to define the pathology of vascular
      changes in glaucoma.

PMID- 9290383
TI  - Cavernous haemangioma of the iris in a leprosy patient.

PMID- 9290385
TI  - Intraepithelial sebaceous neoplasia invading the lacrimal gland.

PMID- 9290384
TI  - Sympathetic ophthalmia from inadvertent ocular perforation during conventional
      retinal detachment surgery.

PMID- 9290386
TI  - The oculocardiac reflex in cataract surgery in the elderly.

PMID- 9290388
TI  - Fast or slow pathway ablation (or neither) for AV nodal tachycardia?

PMID- 9290387
TI  - Slow potentials and catheter ablation for AVNRT.

PMID- 9290389
TI  - Jean Nicolas Corvisart (1755-1821).

PMID- 9290390
TI  - The evidence base for the cost effectiveness of cardiac rehabilitation.

PMID- 9290391
TI  - Images in cardiology. Cardiac sarcoidosis.

PMID- 9290392
TI  - Flow associated or flow mediated dilatation? More than just semantics.
AB  - Dilatation of the brachial artery occurs after flow is increased, and an
      attenuation in this response is seen in subjects with cardiovascular risk
      factors, and in those with established coronary artery disease. The mechanisms
      linking ischaemia, flow changes, and brachial artery dilatation are unclear, and
      it is not known how these are affected by arterial disease. For the present it
      might be more appropriate to refer to flow associated rather than flow mediated
      dilatation, to describe the phenomenon in the brachial artery. Despite these
      caveats, the non-invasive measurement of brachial artery following ischaemic
      dilatation represents a significant advance, and its suitability as a surrogate
      marker for coronary artery dysfunction appears promising. The technique has
      potential as a tool for screening those at high risk of vascular disease, and as
      a surrogate endpoint in intervention studies. Further research should clarify the
      mechanisms involved, and lead to greater insights into the nature of endothelial
      dysfunction and cardiovascular disease.

PMID- 9290393
TI  - Family planning requirements of adults with congenital heart disease.

PMID- 9290395
TI  - Management of adults with congenital heart disease.

PMID- 9290394
TI  - Pregnancy and congenital heart disease.

PMID- 9290396
TI  - Outcome of pregnancies in patients with complex pulmonary atresia.
AB  - OBJECTIVE: To evaluate the outcome of pregnancies in patients with complex
      pulmonary atresia, comparing those with and without previous radical surgical
      repair. DESIGN: A retrospective study of all pregnancies in women with complex
      pulmonary atresia registered on the Grown-up Congenital Heart Unit database
      between 1977 and 1994. SETTING: Referral centre for adolescents and adults with
      congenital heart disease. PATIENTS: Forty one pregnancies occurred in 15
      patients. They were divided into two groups; group I, 26 pregnancies in nine
      patients before radical repair (cyanotic); group II, 15 pregnancies in seven
      women after radical surgical repair. RESULTS: In group I there were three
      terminations, 13 miscarriages, eight healthy children, and two neonatal deaths.
      Five children were born prematurely and all had low birthweights. In group II
      there were two miscarriages, 11 normal children, and two children with congenital
      heart disease. None was premature and all had normal birthweights. There were
      major complications in both groups: in group I there were two thromboembolic
      complications and one episode of heart failure; in group II there was one
      pulmonary embolism and one arrhythmic complication, five pregnancies in three
      patients were complicated by left ventricular failure that was persistent in one
      case and progressive in another, leading to death 13 months after delivery.
      CONCLUSIONS: Patients with complex pulmonary atresia, with or without surgical
      repair, who have no or mild symptoms, can have successful pregnancies. Surgical
      repair decreases fetal complications significantly. In both groups thrombotic
      disorders and heart failure must be prevented. Patients with residual systemic
      pulmonary collaterals after surgical repair are particularly at risk of left
      ventricular failure.

PMID- 9290398
TI  - Thrombolytic treatment for myocardial infarction: an examination of practice in
      39 United Kingdom hospitals. Myocardial Infarction Audit Group.
AB  - OBJECTIVE: To examine use of thrombolytic drugs for myocardial infarction and use
      of contraindications to treatment in the United Kingdom. DESIGN: Observational
      study, based on a continuing audit. SETTING: 39 hospitals in the United Kingdom.
      PATIENTS: 30,029 patients admitted between November 1992 and June 1995 with
      suspected myocardial infarction. RESULTS: Of 13,628 patients with a final
      diagnosis of definite myocardial infarction 10,316 (75.7%) were considered
      eligible for thrombolytic treatment on the basis of typical cardiographic changes
      or new left bundle branch block. Of these, 8139 (59.7%) were diagnosed at
      admission to hospital and 6991 (85.9%) were administered thrombolytic drugs;
      14.1% were considered too late for treatment or had a clinical contraindication.
      In 2177 patients (16% of 13,628)-thrombolytic treatment was given in the absence
      of contraindications and after the diagnosis of infarction had been confirmed by
      further electrocardiographic evidence. A further 591 (4.3%) with a final
      diagnosis of definite infarction without typical cardiographic changes also
      received thrombolytic treatment as did 1018 patients without a final diagnosis of
      definite infarction. In total, 9459 of 13,628 patients (71.6%) received
      thrombolytic treatment. The range of use of treatment between hospitals for a
      final diagnosis of infarction was 49.1-85.4%. This variation reflected
      differences in the frequency with which a diagnosis of definite myocardial
      infarction was made at admission, and the subsequent use of clinical
      contraindications to thrombolytic treatment. CONCLUSIONS: 75.7% of patients with
      a final diagnosis of definite myocardial infarction were eligible for
      thrombolytic treatment on the basis of cardiographic changes. Differences between
      hospitals in the frequency with which a diagnosis of infarction was made on
      admission, and differences in subsequent use of thrombolytic drugs, results in
      wide variation in treatment rates. Differences in use of thrombolytic treatment
      mainly reflect different thresholds for the use of clinical contraindications
      relating to haemorrhagic risk.

PMID- 9290397
TI  - Non-invasive measurement of endothelial function: effect on brachial artery
      dilatation of graded endothelial dependent and independent stimuli.
AB  - OBJECTIVE: To examine the relation between endothelial dependent and endothelial
      independent stimuli of varying intensity and measures of vascular function in the
      brachial artery of young healthy adults, to determine whether these responses are
      consistent and can be used to assess endothelial function. DESIGN AND SETTING:
      High resolution ultrasound was used to measure brachial artery diameter at rest,
      after reactive hyperaemia induced by forearm cuff occlusion, and after sublingual
      isosorbide dinitrate (ISDN). Each subject was assigned to a random order of six
      cuff occlusion times (30 seconds, 1.5, 2.5, 3.5, 4.5, and 8 minutes) and six
      doses of ISDN (10, 20, 50, 100, 200, and 400 micrograms). SUBJECTS: Three males
      and three females mean age 31 years (range 25 to 43) with no known risk factors
      for cardiovascular disease. MAIN OUTCOME MEASURES: Flow mediated, endothelial
      dependent dilatation was compared to duration of cuff occlusion, peak reactive
      hyperaemia, and duration of increased flow. Nitrate induced, endothelial
      independent dilatation was compared to dose of ISDN and change in flow. RESULTS:
      Vessel dilatation and duration of peak flow change increased with longer duration
      of cuff occlusion. After 4.5 minutes of occlusion, flow mediated dilatation was
      mean (SD) 96 (6)% of maximal response and did not increase significantly with
      longer occlusion times. No significant dilatation occurred after 10 or 20
      micrograms of ISDN in any subject. With increasing doses up to 200 micrograms
      there was an increase in dilatation. Endothelial independent dilatation did not
      increase significantly with doses of ISDN above 200 micrograms. CONCLUSIONS:
      Measures of arterial function vary with duration of blood flow occlusion and ISDN
      dose. Maximum arterial response was reached in all subjects after 4.5 minutes of
      blood flow occlusion or 200 micrograms of ISDN. Therefore, these variables
      produce consistent reproducible measures of endothelial function.

PMID- 9290399
TI  - Prospective study of the value of necropsy examination in early death after
      cardiac surgery.
AB  - OBJECTIVE: To assess the value of necropsy examination in patients dying soon
      after cardiac surgery, particularly the proportion of clinical questions answered
      by the necropsy, the frequency of major unexpected findings, and the limitations
      of the procedure. DESIGN: A three year prospective study of necropsy examinations
      in adult patients dying before discharge or within 30 days of cardiac surgery
      performed under cardiopulmonary bypass in one hospital. SETTING: Tertiary
      referral centre. RESULTS: 123 of 2781 patients (4.4%) died in the early
      postoperative period, and necropsy examination was performed in 108 of these
      (88%). The mortality after emergency procedures (18%) was much higher than after
      routine operations (2.6%). The main causes of death were cardiac failure (52%),
      haemorrhage (14%), cerebral disease (6%), and pulmonary emboli (5%). The necropsy
      changed the stated cause of death in 16 patients (15%), and answered clinical
      questions in 24 of 38 patients. In 15 patients necropsy examination did not
      provide a full explanation of death. Most of these patients died of cardiac
      failure soon after surgery or were sudden unexpected deaths. CONCLUSIONS:
      Necropsy examination in patients dying early after cardiac surgery is valuable as
      it answers the majority of clinical questions, and shows unexpected findings in a
      significant proportion of cases.

PMID- 9290400
TI  - Relation between serum uric acid and lower limb blood flow in patients with
      chronic heart failure.
AB  - OBJECTIVE: To determine whether lower limb blood flow is related to serum uric
      acid concentrations in patients with chronic heart failure, taking into account
      the hyperuricaemic effects of diuretic treatment and insulin resistance. DESIGN:
      Lower limb blood flow was measured at rest and after maximum exercise followed by
      a five minute period of ischaemia (maximum blood flow) using strain gauge venous
      occlusion plethysmography. All patients underwent a metabolic assessment, which
      included an intravenous glucose tolerance test (IVGTT)-to obtain an index of
      insulin sensitivity- and measurement of serum uric acid. SETTING: University and
      hospital departments specialising in cardiology and metabolic medicine. SUBJECTS:
      22 patients with chronic heart failure. RESULTS: Mean (SEM) resting and maximum
      blood flow values were 2.87 (0.23) and 24.00 (1.83) ml/100 ml/min, respectively.
      Patients in the upper tertile of serum uric acid had lower maximum blood flow
      than those in the lowest tertile (15.6 (2.2) v 31.0 (2.1) ml/100 ml/min, P =
      0.003). Serum uric acid correlated with maximum blood flow (r = -0.86, P <
      0.001), but not with resting blood flow. In stepwise regression analysis, uric
      acid emerged as the only predictor of maximum blood flow (standardised
      coefficient = -0.83 (P < 0.001), R2 = 0.68 (P < 0.001)), independently of
      diuretic dose, age, body mass index, plasma creatinine, fasting and IVGTT glucose
      and insulin, insulin sensitivity, maximum oxygen uptake and exercise time during
      the treadmill exercise test, and alcohol intake. CONCLUSIONS: There is a strong
      inverse relation between serum uric acid concentrations and maximum leg blood
      flow in patients with chronic heart failure. Further studies are needed to
      determine whether serum uric acid can be used as an index of vascular function in
      cardiovascular diseases.

PMID- 9290401
TI  - Risk for atrial fibrillation in patients with hypertrophic cardiomyopathy
      assessed by signal averaged P wave duration.
AB  - OBJECTIVE: To assess the relation between P wave duration and the occurrence of
      atrial fibrillation in hypertrophic cardiomyopathy (HCM). DESIGN: High resolution
      signal averaged electrocardiography was used in 110 patients with HCM to
      determine whether patients at risk for paroxysmal atrial fibrillation could be
      detected during sinus rhythm by measuring P wave duration. Filtered P wave
      duration was measured manually, over an average of 300 beats per patient.
      RESULTS: During follow up, 18 patients (16%) had at least one one clinical
      episode of paroxysmal atrial fibrillation, including four patients whose initial
      episode followed the signal averaged electrocardiogram. The 18 patients with
      overt atrial fibrillation had greater P wave duration than the 69 patients who
      did not develop atrial fibrillation: 150 (SD 20) v 126 (14) ms; P < 0.001.
      Another 23 patients without clinically evident atrial fibrillation had prolonged
      bursts of the arrhythmia on Holter recording, and showed a P wave duration (138
      (15) ms) intermediate between patients with and without clinical atrial
      fibrillation. In assessing risk for atrial fibrillation, P wave duration > or =
      140 ms was associated with sensitivity, specificity, and positive predictive
      accuracy values of 56%, 83%, and 66%. Multivariate analysis showed that duration
      of the P wave was the only independent variable associated with occurrence of
      atrial fibrillation; if P wave duration > or = 140 ms was combined with left
      atrial enlargement > 40 mm, the specificity and positive predictive accuracy for
      atrial fibrillation increased to 93% and 78%. CONCLUSIONS: Measurement of P wave
      duration in sinus rhythm by high resolution signal averaged electrocardiography
      may be a useful non-invasive clinical tool for identifying patients with HCM
      likely to develop electrical instability and atrial fibrillation.

PMID- 9290402
TI  - Combined use of non-thoracotomy cardioverter defibrillators and endocardial
      pacemakers.
AB  - OBJECTIVE: To study the potential interactions in patients with endocardial
      permanent pacemakers and non-thoracotomy implantable cardioverter defibrillator
      (ICD) systems. DESIGN: Case series and cohort study. SETTING: Tertiary referral
      centre. PATIENTS: Fifteen consecutive patients with both endocardial pacemakers
      (12 dual chamber and three single chamber) and non-thoracotomy ICD systems. MAIN
      OUTCOME MEASURES: Detection inhibition of induced ventricular fibrillation;
      double counting; and pacemaker function after shocks. In the evaluation of
      detection inhibition, 124 VF inductions were analysed for detection duration
      compared with induced VF episodes in controls with an ICD but without a
      pacemaker. RESULTS: Two patients (13%) showed detection inhibition of VF and
      required pacemaker system change at the time of the ICD implant. With the final
      lead position, despite frequent pacemaker undersensing of VF, ICD detection of VF
      was not inhibited during any induction, and neither initial detection nor
      redetection times for VF were different from controls. Double/triple counting of
      pacemaker artefact and evoked electrogram was noted in three patients (20%). In
      two, this was remedied during the implantation procedure, and in the other it was
      abolished when amiodarone treatment was discontinued. Pacemaker function was
      affected by ICD discharges in two patients, one who showed postshock atrial
      undersensing and loss of capture, and another whose pacemaker reverted to VVI
      mode. CONCLUSIONS: When careful testing is performed at implantation to detect
      and remedy device interactions, non-thoracotomy ICD treatment and endocardial
      pacemakers can be used safely in combination.

PMID- 9290403
TI  - Can abnormalities of ventricular repolarisation identify insulin dependent
      diabetic patients at risk of sudden cardiac death?
AB  - OBJECTIVE: To study the possible association or QT dispersion and mean QTc
      intervals, as measured from standard 12 lead electrocardiograms, with
      baroreceptor-cardiac reflex sensitivity (BRS) in insulin dependent diabetic
      patients. DESIGN: Comparative study of non-invasive assessment of BRS, QT
      interval, and QT dispersion. SETTING: Large teaching hospital. SUBJECTS: 31 young
      asymptomatic, normotensive, insulin dependent diabetic patients, aged 20-55 years
      with normal clinical autonomic function. METHODS: QT intervals and QT dispersion
      were measured by a single observer blinded to other data about the patients. BRS
      was measured after activating the baroreflex with a Valsalva manoeuvre, and the
      rate in change of R-R interval to increasing systolic pressure during phase 4 was
      measured; in addition sequence analysis of resting systolic blood pressure and
      heart rate was performed during standing. The alpha coefficient--an index of the
      overall gain of the baroreflex mechanisms--was estimated from spectral analysis
      data of systolic blood pressure and pulse interval variability. RESULTS: Mean
      (SD) QTc interval was 406 (23) ms, QT dispersion was 44 (13) ms. There was no
      association between QT dispersion and any measurement of BRS. There was a
      negative correlation between mean QTc intervals and sequence analysis BRS (r = 
      0.355, P = 0.049), but no association with Valsalva BRS. The alpha coefficient,
      showed a significant negative correlation with mean QTc (r = -0.42, P = 0.008).
      CONCLUSIONS: Abnormal BRS may be reflected in the heart by global prolongation of
      ventricular repolarisation, but not by dispersion of ventricular repolarisation.
      This may, in part, explain the increase in sudden cardiac death seen in IDDM
      patients.

PMID- 9290404
TI  - Impairment of the myocardial vasomotor response to cold pressor stress in
      collateral dependent myocardium.
AB  - OBJECTIVE: To study the vasomotor response (cold pressor/basal flow) in
      myocardium perfused entirely by collaterals, using the reflex sympathetic
      stimulation of cold pressor stress. DESIGN: Regional myocardial blood flow was
      measured in collateral dependent and in remote myocardium using positron emission
      tomography with 15O water at basal and at cold pressor stress. Regional ischaemia
      was measured with 18F-fluorodeoxyglucose (FDG). PATIENTS: Nine patients (mean
      (SD) age 53 (6) years) with an occluded coronary artery supplied entirely by
      collaterals from other angiographically normal arteries. RESULTS: In remote
      myocardium, basal and cold pressor flow were 0.99 (0.26) and 1.46 (0.60) ml/min/g
      (P < 0.05), respectively, a myocardial vasomotor response of 1.46 (0.45). In
      collateral dependent myocardium, basal and cold pressor flow were 0.91 (0.20) and
      0.87 (0.35) ml/min/g, respectively (the latter value, P < 0.05 v remote region),
      a myocardial vasomotor response of 0.97 (0.43) (P < 0.05 v remote region). The
      myocardial vascular resistance (mean arterial pressure/flow) during cold pressor
      was higher in the collateral dependent than in remote myocardium, at 147.0 (61.1)
      and 85.6 (32.3) mm Hg.min.g/ml (P < 0.05), respectively, but with no relative
      increase in FDG uptake. CONCLUSIONS: In contrast to the decrease in myocardial
      resistance in remote myocardium with cold pressor, an increase was observed in
      collateral dependent myocardium suggesting a vasoconstrictor response in
      resistive vessels, without demonstrable myocardial ischaemia.

PMID- 9290405
TI  - Planimetry of aortic valve area using multiplane transoesophageal
      echocardiography is not a reliable method for assessing severity of aortic
      stenosis.
AB  - OBJECTIVE: To assess the reliability of aortic valve area planimetry by
      multiplane transoesophageal echocardiography (TOE) in aortic stenosis. DESIGN:
      Study of the diagnostic value of aortic valve area planimetry using multiplane
      TOE, compared with catheterisation and the continuity equation, both being
      considered as criterion standards. SETTING: University hospital. PATIENTS: 49
      consecutive patients (29 male, 20 female, aged 44 to 82 years, average 66.6 (SD
      8.5)), referred for haemodynamic evaluation of an aortic stenosis, were enrolled
      in a prospective study. From this sample, 37 patients were eligible for the final
      analysis. METHODS: Transthoracic and multiplane transoesophageal echocardiograms
      were performed within 24 hours before catheterisation. At transthoracic echo,
      aortic valve area was calculated by the continuity equation. At TOE, the image of
      the aortic valve opening was obtained with a 30-65 degrees rotation of the
      transducer. Numerical dynamic images were stored on optical discs for off-line
      analysis and were reviewed by two blinded observers. Catheterisation was
      performed in all cases and aortic valve area was calculated by the Gorlin
      formula. RESULTS: Feasibility of the method was 92% (48/52). The agreement
      between aortic valve area measured at TOE (mean 0.88 (SD 0.35) cm2) and at
      catheterisation (0.79 (0.24) cm2) was very poor. The same discrepancies were
      found between TOE and the continuity equation (0.72 (0.26) cm2). TOE planimetry
      overestimated aortic valve area determined by the two other methods. Predictive
      positive and negative values of planimetry to detect aortic valve area < 0.75 cm2
      were 62% (10/16) and 43% (9/21) respectively. CONCLUSIONS: Planimetry of aortic
      valve area by TOE is difficult and less accurate than the continuity equation for
      assessing the severity of aortic stenosis.

PMID- 9290406
TI  - Familial and primary (AL) cardiac amyloidosis: echocardiographically similar
      diseases with distinctly different clinical outcomes.
AB  - OBJECTIVE: To determine whether patients with myocardial amyloidosis due either
      to AL (primary) amyloid or familial amyloid have distinguishing echocardiographic
      or electrocardiographic features; and to compare the prevalence of heart failure
      and survival in the two types of amyloidosis in relation to echocardiographic
      findings. DESIGN: Blinded group comparison of randomly selected cases of cardiac
      amyloidosis. SETTING: International referral centre for amyloid research and
      treatment. PATIENTS: 36 patients with cardiac amyloid heart disease, of whom 12
      had familial and 24 had primary AL amyloidosis. RESULTS: Familial and AL
      echocardiograms were morphologically indistinguishable, with similar left
      ventricular wall thickness, mean (SD) 15.4 (2.3) nu 15.8 (2.5) mm, respectively;
      right ventricular wall thickness was also similar between amyloid types: 9.6
      (2.8) nu 9.7 (6.5) mm, respectively. Doppler indices of left and right
      ventricular function, left ventricular volume, and ejection fraction were also
      similar. Low voltage electrocardiograms (< 0.5 mV) were more common in the AL
      (16/24, 67%) than in the familial group (4/12, 25%), P < 0.05. The one year
      survival for familial and AL forms was 92% (11/12) nu 38% (6/24), respectively,
      with virtually all deaths due to cardiac causes. CONCLUSIONS: Although cardiac
      involvement is echocardiographically indistinguishable, cardiac mortality is very
      different between the two forms of amyloidosis. Preservation of
      electrocardiographic voltage in familial amyloidosis suggests that the particular
      biochemical characteristics of distinct types of amyloid fibril have different
      pathological effects on the myocardium. This distinction becomes critical in the
      evaluation, treatment, and management of patients who have a diagnosis within the
      spectrum of the protein deposition diseases.

PMID- 9290408
TI  - Images in cardiology. Non-invasive detection of quadricuspid aortic valve.

PMID- 9290407
TI  - Congenital quadricuspid aortic valve anomaly associated with hypertrophic non
      obstructive cardiomyopathy: a case report and review of the literature.
AB  - A case is reported of a 38 year old woman without known cardiac congenital
      abnormality but a history of well controlled arterial hypertension who was
      admitted to hospital after successful resuscitation at home following cardiac
      arrest. There was no evidence of myocardial infarction on 12-lead
      electrocardiogram but there were signs of left ventricular hypertrophy.
      Transoesophageal echocardiography revealed a rare quadricuspid aortic valve (QAV)
      malformation with concomitant mild aortic regurgitation. The left ventricle
      showed a massive concentric hypertrophy without obstruction. The patient was
      eventually transferred in a persistent vegetative state to a home care facility.
      A review of the literature revealed 70 cases of QAV diagnosed by transthoracic or
      transoesophageal echocardiography (26 cases), at necropsy (25), during surgery
      (15), and during angiography (4). The present case is the first report of QAV
      associated with non-obstructive hypertrophic cardiomyopathy.

PMID- 9290409
TI  - Myocardial infarction related atrial fibrillation: role of endogenous adenosine.
AB  - Exogenous administration of adenosine induces atrial fibrillation in up to 7.0%
      of patients. Animal studies affirm endogenous adenosine released in response to
      tissue hypoxia may play a mechanistic role in arrhythmias associated with
      myocardial ischaemia or hypoxia. Therefore, atrial fibrillation occurring early
      after the acute phase of myocardial infarction involving atrial tissue may be
      secondary to an excessive accumulation of adenosine that leads to a shortening of
      atrial refractory period. Early in the course of acute inferior myocardial
      infarction, two patients (males aged 45 and 68) suffered new onset sustained
      atrial fibrillation that was abrupt in onset and complicated their clinical
      management. They were administered 250 mg theophylline as a slow intravenous
      injection at a rate of 100 mg/min or until conversion to normal sinus rhythm
      occurred. Both patients converted to normal sinus rhythm within five minutes of
      the administration of theophylline. In up to 52 hours of continuous ECG
      monitoring after the theophylline administration the atrial fibrillation did not
      recur. Neither patient experienced any adverse outcome from theophylline
      administration. These observations are the first reported in humans or laboratory
      animals to suggest that atrial fibrillation, presumably due to elevated
      interstitial atrial concentration of adenosine caused by myocardial ischaemia,
      can be terminated with an adenosine receptor antagonist. However, the hypothesis
      that excessive accumulation of endogenous adenosine in atrial tissue may induce
      atrial fibrillation is well substantiated by other investigators. Thus, A1
      adenosine receptor antagonists may prove to be valuable in the management of
      ischaemia related atrial fibrillation.

PMID- 9290410
TI  - Multiple coronary artery-left ventricular fistulae: haemodynamic quantification
      by intracoronary Doppler ultrasound.
AB  - Multiple coronary artery-left ventricular fistulae involving all three major
      coronary arteries are extremely rare. Clinical findings are heterogeneous but
      include a history of typical or atypical angina pectoris in most cases. Coronary
      arteriography in a 65 year old woman who presented with chest pain at rest
      revealed multiple fine fistulae arising from the left anterior descending, left
      circumflex, and right coronary arteries. Left-to-left shunt was estimated by
      measurements of coronary artery flow velocity with intravascular Doppler
      ultrasound.

PMID- 9290411
TI  - Intractable vasospastic angina.

PMID- 9290412
TI  - Outcome of isolated congenital heart block diagnosed in utero.

PMID- 9290413
TI  - Bidirectional superior cavopulmonary anastomosis: how young is too young?

PMID- 9290414
TI  - Seven research projects for South Africa.

PMID- 9290415
TI  - The medical profession and justice. Nuffield lecture.

PMID- 9290416
TI  - Paracetamol hepatotoxicity: how to prevent.

PMID- 9290417
TI  - Risk factors for basal cell carcinoma in the UK: case-control study in 806
      patients.
AB  - Basal cell carcinoma (BCC) is the commonest malignant neoplasm in white people.
      We present a large UK case-control study in which conditional logistic regression
      analysis of age-matched and gender-matched data sets was used to compare, first,
      cases with controls (n = 403) and second, patients having multiple BCC with those
      having a single BCC (n = 278). Eye/hair colour, occupation, skin type, social
      class, tumour site at presentation and smoking history were assessed. Social
      class 1/2, skin type 1, red/blonde hair and blue/green eyes were all related to
      BCC risk, social class most strongly (odds ratio 2.36, P = 0.007). Truncal site
      at presentation was a risk factor for the development of multiple BCC (odds ratio
      4.03, P = 0.002). These data support the view that genetically mediated
      differences in ultraviolet responsiveness are important in BCC, though the scale
      of their effect is small. They may be exploitable in primary and secondary
      prevention as well as giving insights into pathogenesis. In particular, the fact
      that patients presenting with a truncal tumour are at increased risk of further
      BCC suggests that intermittent exposure in genetically predisposed individuals
      may contribute to a cancer susceptibility syndrome.

PMID- 9290418
TI  - Effect of anorectal eversion on long-term clinical outcome of restorative
      proctocolectomy.
AB  - Eversion of the rectum during restorative proctocolectomy with stapled ileal
      pouch-anal anastomosis (IPAA) remains a controversial surgical manoeuvre because
      of concern that it may impair anal sphincter function and adversely affect
      outcome. We have reviewed the long-term results in 41 patients whose operation
      included formation of a 20 cm J-pouch with stapled IPAA by the technique of
      rectal eversion. At median follow-up of 4 years (range 1-6 years), 4 pouches
      (10%) had been removed (2 for pelvic sepsis, 1 for rectovaginal fistula and 1 for
      Crohn's disease). In 34 patients with functioning pouches in situ, median stool
      frequency was 5 per 24 h (range 2-10). 11 patients (33%) regularly had to
      evacuate their pouch at night and 4 (12%) used antidiarrhoeal medication. No
      patients reported major incontinence; 2 (6%) had minor leakage, and in another 2
      minor leakage had now ceased. 4 patients had had episodes of pouchitis. These
      favourable results offer no support for the contention that rectal eversion
      substantially worsens the long-term results of restorative proctocolectomy.

PMID- 9290419
TI  - Assembling comparison groups to assess the effects of health care.

PMID- 9290420
TI  - Is there a role for surgery in small-cell lung cancer?

PMID- 9290422
TI  - Horner's syndrome due to herpes zoster in the T3-T4 dermatome.

PMID- 9290421
TI  - Fever--concepts old and new.

PMID- 9290423
TI  - A syllabus for evolutionary medicine.

PMID- 9290424
TI  - Diseases of consciousness?

PMID- 9290425
TI  - Female genital mutilation: a contemporary issue, and a Victorian obsession.

PMID- 9290426
TI  - Destruction of a hospital.

PMID- 9290427
TI  - Coronary heart disease in Africa.

PMID- 9290428
TI  - Foodborne triggers for epileptic attacks.

PMID- 9290429
TI  - Quality in general practice.

PMID- 9290430
TI  - Abdominal pain and psychosis.

PMID- 9290431
TI  - Hospital at home--which way will it go?

PMID- 9290432
TI  - Diabetes and Queen Anne.

PMID- 9290433
TI  - Scurvy, Lancaster, Lind, Scott and Almroth Wright.

PMID- 9290434
TI  - Hippocratic opinion.

PMID- 9290435
TI  - Schubert's last illness.

PMID- 9290436
TI  - The patient advocate.
AB  - The business environment in which we practice is changing. Social and medical
      problems of women continue for large numbers of our population. The obstetrician
      gynecologist as the primary care provider for women must be active as the
      patient's advocate in the areas of sex education, contraceptive counseling,
      teenage pregnancy, domestic violence, healthy lifestyles, and decisions regarding
      appropriate health care.

PMID- 9290438
TI  - Clinical predictors of urinary incontinence in women.
AB  - OBJECTIVE: Our purpose was to characterize historic and clinical parameters in
      incontinent women to determine the predictive value for urodynamic diagnoses.
      STUDY DESIGN: The analysis includes 535 consecutive women with final diagnoses of
      genuine stress incontinence, detrusor instability, or both. Evaluations included
      a standardized history, examination, urinary diary, quantitation test, and
      urodynamics. The analysis used one-way analysis of variance, chi 2 analysis with
      Yates' correction, and Fisher's exact test. RESULTS: A total of 351 (66%) women
      were diagnosed with genuine stress incontinence, 102 (19%) with detrusor
      instability, and 82 (15%) with both. Half had symptoms of both stress
      incontinence and urge incontinence, of whom only 21% had both genuine stress
      incontinence and detrusor instability. Fewer than half of women diagnosed with
      genuine stress incontinence or detrusor instability had just symptoms of stress
      incontinence or urge incontinence, respectively. Evaluation of historic,
      examination, and urinary diary data for their influences on the predictive value
      of pure stress incontinence or urge incontinence revealed statistical differences
      for urethral hypermobility, estrogen deficiency, and incontinent episodes, yet
      they were not clinically practical predictors. CONCLUSIONS: Pure symptoms
      identify fewer than half of patients with pure genuine stress incontinence or
      detrusor instability; historic and clinical parameters do not improve the
      sensitivity of these symptoms.

PMID- 9290437
TI  - The effect of indomethacin tocolysis on fetal ductus arteriosus constriction with
      advancing gestational age.
AB  - OBJECTIVE: Our purpose was to determine whether continuing exposure to
      indomethacin tocolysis is associated with an increased incidence of constriction
      of the human fetal ductus arteriosus with advancing gestational age. STUDY
      DESIGN: Fetal echocardiograms were reviewed in 61 cases in which the pregnant
      women were treated for preterm labor with indomethacin (25 mg orally every 6
      hours). Density function analysis and regression analysis were used to assess the
      effect of indomethacin tocolysis on ductal constriction with advancing
      gestational age. RESULTS: A total of 193 fetal echocardiograms were obtained for
      72 fetuses. Ductal constriction developed in 50% of the fetuses ranging from 24.7
      to 35.0 weeks' gestation. Fetuses with indomethacin-induced ductal constriction
      demonstrated a greater increase in systolic flow velocities with advancing
      gestational age compared with the nonconstricted group (p < 0.05). Constriction
      was detected at a mean gestational age of 30.9 +/- 2.3 weeks at an average of 5.1
      +/- 6.0 days after initiation of therapy. Ductal constriction occurred by 31
      weeks' gestation in 70% of the affected fetuses. After discontinuation of
      indomethacin therapy, all follow-up echocardiograms demonstrated a return to
      nonconstricted ductal flow velocities. No significant adverse neonatal outcomes
      were attributed to indomethacin use. CONCLUSIONS: A dramatic yet reversible
      increase in the incidence of indomethacin-induced ductal constriction occurs at
      31 weeks' gestation. However, ductal constriction can occur at any gestational
      age. With indomethacin tocolysis, weekly fetal echocardiography is warranted for
      the duration of therapy.

PMID- 9290439
TI  - Characteristics of successful claims for payment by the Florida Neurologic Injury
      Compensation Association Fund.
AB  - OBJECTIVES: Our purpose was to examine the obstetric characteristics of claims
      paid by the State of Florida after the birth of a neurologically impaired child.
      STUDY DESIGN: The Florida Birth Related Neurological Injury Compensation plan is
      a no-fault alternative to litigation for compensation after a catastrophic
      neurologic birth injury. The plan has specific criteria for inclusion. We
      retrospectively analyzed claims for compensation that were accepted and paid (n =
      64) after a birth-related neurologic injury. Simple description statistics were
      compiled for the relative frequencies of various obstetric correlates found in
      successful claims for payment. RESULTS: Seventy percent of infants (45) were
      delivered by cesarean section and 15 of 19 vaginal deliveries (79%) were
      operative (forceps or vacuum), yielding a 94% operative delivery rate. A
      persistent nonreassuring fetal heart rate tracing was seen before delivery in all
      cases. The 5-minute Apgar score was < or = 6 in 91% of deliveries and the 10
      minute Apgar score was < 6 in 86% of deliveries. When first examined in the labor
      and delivery suite, 17 women had a nonreassuring fetal heart rate, and a
      nonreassuring tracing developed in labor in 47. Nine attempts at vaginal birth
      after a cesarean section led to a uterine rupture. Seven of these deliveries were
      either inductions or augmentations against an unfavorable cervix. Forty-five
      percent (27) of deliveries were associated with meconium-stained amniotic fluid,
      including 17 infants with meconium aspiration syndrome. There were three shoulder
      dystocias and four infants with group B streptococcal sepsis. In eight cases
      (12.5%), there appeared to be a breach of the published standard of care, which
      contributed to the poor outcome. CONCLUSION: Most of these cases should not have
      been eligible for compensation in a traditional tort-based system because the
      applicable standard of care was not breached. Meeting the published standard for
      perinatal care failed to prevent these devastating neurologic injuries.
      Obviously, not all intrapartum injuries can be prevented; however, if we are to
      prevent similar injuries in the future, we will need to examine the clinical
      management in these or similar case for clues to develop novel strategies to
      respond to intrapartum emergencies. An unexpected finding was the frequency of
      catastrophic birth injuries after an attempted vaginal birth after cesarean
      section with the predominance of these deliveries associated with oxytocin
      stimulation against an unripe cervix. It is apparent that the push to lower
      cesarean section rates is not without some risk.

PMID- 9290441
TI  - Parental rights at the birth of a near-viable infant: conflicting perspectives.
AB  - OBJECTIVE: Our purpose was to clarify the roles of parents and caregivers in
      making decisions for resuscitation of near-viable infants. STUDY DESIGN: We
      present two cases and review ethical and legal issues involved in making
      decisions for near-viable infants. RESULTS: Medical responsibility for the infant
      shifts at birth from obstetrics to neonatology. Neonatologists will "opt for
      life" when prognosis is uncertain. As surrogate decision makers, parents have
      rights to make decisions about initiation of resuscitation, but these parental
      rights are limited by the infant's best interests. If caregivers believe parents
      are not acting in the infant's best interests, they may persuade parents,
      challenge parental refusal by petitioning the courts, or treat without consent
      with possible legal risk. CONCLUSIONS: Effective communication is essential to
      prevent misunderstanding and conflicts. In most instances parents are the best
      decision makers for a near-viable infant. Parental rights are limited by best
      interests of the infant.

PMID- 9290440
TI  - The etiology of fetal acidosis as determined by umbilical cord acid-base studies.
AB  - OBJECTIVE: Our purpose was to determine whether umbilical cord acid-base values
      might be used to differentiate abruptio placentae from cord prolapse. STUDY
      DESIGN: By use of a retrospective study design, umbilical cord blood acid-base
      values of 32 cases of severely acidotic acute abruptio placentae were
      statistically compared with those of 19 cases of severely acidotic acute cord
      prolapse with Fisher's exact test, Mann-Whitney U tests, and receiver-operator
      curve characteristic analyses. RESULTS: No significant differences in electronic
      fetal heart rate record interpretations were detected. Highly significant
      differences in umbilical arterial and umbilical venous blood gas values were
      noted between the two groups. Most notable were the differences between umbilical
      venous and arterial blood gas values in the cord prolapse group. Receiver
      operator characteristic curve analysis demonstrated that an umbilical venous
      arterial pH difference of 0.15 was an effective cutoff value in differentiating
      cord prolapse from abruptio placentae (accuracy 92%). CONCLUSION: Umbilical
      arterial blood gas values combined with umbilical venous blood gas values can
      assist in determining the pathogenesis of marked fetal acidosis.

PMID- 9290442
TI  - Ultrasonographic assessment of amniotic fluid does not reflect actual amniotic
      fluid volume.
AB  - OBJECTIVE: Our objective was to compare the ability of two methods of amniotic
      fluid assessment (two-diameter amniotic fluid pocket versus the amniotic fluid
      index) to predict oligohydramnios (actual amniotic fluid volume < 500 ml) or
      polyhydramnios (actual amniotic fluid volume > 1500 ml). STUDY DESIGN: The
      amniotic fluid index and the two-diameter amniotic fluid pocket were assessed
      before amniocentesis and determination of amniotic fluid volume with the dye
      (aminohippurate sodium)-dilution technique. To assess the detection of either
      oligohydramnios or polyhydramnios, the areas under the receiver-operator
      characteristic curves (+/-SE) were estimated by the point-to-point trapezoidal
      method of integration. Prediction limits were calculated by regression analysis
      of amniotic fluid index or two-diameter amniotic fluid pocket versus actual
      amniotic fluid volume and determination of 95th percentile ranges for amniotic
      fluid volume. RESULTS: We studied 144 patients with a mean (+/-SD) gestational
      age of 31.7 +/- 5.5 weeks; mean (+/-SD) amniotic fluid index and two-diameter
      amniotic fluid pocket were 12.6 +/- 6.1 cm and 21.2 +/- 18.4 cm2, respectively.
      Mean (+/-SD) actual amniotic fluid volume was 722 +/- 735 ml (range 101 to 4318
      ml). The areas under the four receiver-operator characteristic curves were not
      significantly different from the nondiagnostic line (p < 0.05). Regression slopes
      (r values) for amniotic fluid index and two-diameter amniotic fluid pocket versus
      actual amniotic fluid volume were 0.34 and 0.23, respectively. Calculation of the
      prediction limit for 95% confidence that oligohydramnios is absent requires that
      the amniotic fluid index be 30 cm and the two-dimension amniotic fluid pocket be
      90 cm2, both thresholds of which are currently considered to represent clinical
      polyhdramnios. CONCLUSIONS: Both amniotic fluid index and two-dimension amniotic
      fluid pocket appear to be inaccurate predictors of actual oligohydramnios or
      polyhydramnios when compared with dye-dilution calculations of actual amniotic
      fluid volume.

PMID- 9290443
TI  - Management of low-grade squamous intraepithelial lesions during pregnancy.
AB  - OBJECTIVE: Our purpose was to determine whether prenatal colposcopy is beneficial
      in pregnant women with squamous atypia, atypical squamous cells of undetermined
      significance, or low-grade squamous intraepithelial lesions on an initial
      screening Papanicolaou smear. STUDY DESIGN: A retrospective chart review
      identified a cohort of pregnant patients referred to the colposcopy clinic at
      Carolinas Medical Center between October 1991 and December 1994 with squamous
      atypia, atypical squamous cells of undetermined significance, or low-grade
      squamous intraepithelial lesions. Results of the colposcopic examination,
      cervical biopsy specimens, postpartum evaluation, and postpartum treatment were
      recorded. Descriptive statistics were used to tabulate numbers and percentages
      for all variables with 95% confidence intervals to determine disease progression.
      RESULTS: Prenatal colposcopy was performed on 253 women during the study period.
      The colposcopic impression was normal or consistent with low-grade squamous
      intraepithelial lesions in 235 (93%) of the women. Of the 67 women who had a
      cervical biopsy, 6 had a histologic diagnosis of high-grade squamous
      intraepithelial lesions. Postpartum Papanicolaou smears were obtained in 224
      patients; 71 (32%) were normal, 145 (65%) were unchanged, and 8 (3%) showed high
      grade squamous intraepithelial lesions. Of the 69 patients who had a postpartum
      cervical biopsy, 4 were found to have high-grade squamous intraepithelial
      lesions. Eight of the 10 women with biopsy-proved high-grade squamous
      intraepithelial lesions were compliant with treatment after delivery. Histologic
      examination of the cervix with tissue obtained by either loop conization or cold
      knife conization showed no evidence of invasive carcinoma. CONCLUSION: Squamous
      atypia, atypical squamous, cells of undetermined significance, or low-grade
      squamous intraepithelial lesions on a Papanicolaou smear in a pregnant patient
      does not require colposcopic evaluation during pregnancy. Progression of low
      grade dysplasia to carcinoma during pregnancy is unusual, and no patient in this
      study was found to have invasive cancer.

PMID- 9290444
TI  - Diagnosing intrinsic sphincteric deficiency: comparing urethral closure pressure,
      urethral axis, and Valsalva leak point pressures.
AB  - OBJECTIVES: Our purpose was to compare three measures proposed to diagnose
      intrinsic sphincteric deficiency: maximum urethral closure pressure, Valsalva
      leak point pressure, and straining urethral axis. STUDY DESIGN: A total of 159
      women with pure genuine stress incontinence had the three measures determined in
      a standardized fashion. Critical cutoff values for the Valsalva leak point
      pressure (52 cm) and urethral axis (22 degrees) were established by examining
      relative frequency distribution curves, using closure pressure of 20 as the
      arbitrary benchmark value for the prevalence of intrinsic sphincteric deficiency.
      The distribution of cutoff values is described and differences among the measures
      with respect to risk factors for intrinsic sphincteric deficiency and
      incontinence severity were determined. RESULTS: Half the subjects fell below at
      least one cutoff value, but only 10% fell below all three. Sixty-four percent of
      subjects with either low closure pressure or leak point pressure had low values
      for the other, whereas 21% had discordance between them. Only 53% of subjects
      with low closure pressure and 40% with low leak point pressure had an axis < or =
      22 degrees. Conversely, a substantial portion (36%) of subjects with pure genuine
      stress incontinence without urethral hypermobility had neither low urethral or
      leak point pressures. All three cutoff-values were associated with risk factors
      for intrinsic sphincteric deficiency, but only low closure and leak point
      pressures had significant associations with the severity of incontinence.
      CONCLUSIONS: Intrinsic sphincteric deficiency should be diagnosed by a composite
      of historic, urodynamic, anatomic, and clinical severity criteria. We would
      include a maximum urethral closure pressure < or = 20, a Valsalva leak point
      pressure < or = 50, and a stress urethral axis < or = 20 in this composite.

PMID- 9290445
TI  - Primary care by obstetricians and gynecologists: attitudes of the members of The
      South Atlantic Association of Obstetricians and Gynecologists.
AB  - OBJECTIVE: Our purpose was to determine the extent of primary care delivered by
      obstetrician-gynecologists and compare practice patterns with published primary
      care and preventive service guidelines. STUDY DESIGN: All 277 active fellows of
      The South Atlantic Association of Obstetricians and Gynecologists were mailed a
      self-administered questionnaire. The type of primary care offered by these
      physicians and their attitudes about the training of residents in obstetrics and
      gynecology were surveyed. Physicians were categorized as generalists or
      specialists on the basis of the completion of a fellowship program. Descriptive
      statistics and chi 2 analysis were used for statistical analysis. RESULTS:
      Completed surveys were returned by 82% of the fellows. The majority of the
      respondents perceived their practice as specialty care for women. Generalists
      offered recommended screening services to women of all ages with greater
      frequency than the specialists did (p = 0.05). Both groups did not provide care
      for the chronic medical illnesses most commonly seen in a primary care practice.
      The respondents favored more residency training in those common acute illnesses
      frequently encountered in a primary care setting. CONCLUSIONS: Obstetrician
      gynecologists in The South Atlantic Association of Obstetricians and
      Gynecologists selectively practice primary care. These physicians did not support
      caring for chronic medical problems frequently treated in an ambulatory care
      practice.

PMID- 9290446
TI  - Developmental outcomes of children with myelomeningocele: prenatal predictors.
AB  - OBJECTIVE: The purpose of the current investigation was to determine cognitive
      developmental outcomes for a cohort of children with prenatally detected
      myelomeningocele and to determine whether the variables of (1) severity of
      ventriculomegaly and (2) anatomic level of lesion were predictive of cognitive
      development. STUDY DESIGN: Prenatal ultrasonographic examinations were reviewed
      by a single perinatologist to determine the degree of ventriculomegaly and the
      anatomic level of the lesion. Ventriculomegaly was defined as a lateral
      ventricular atrial width > 10 mm. Anatomic level of lesion was defined as (1)
      thoracic, (2) high lumbar, (3) midlumbar, (4) low lumbar-high sacral, or (5)
      sacral. Cognitive developmental quotients for surviving children were determined
      by one of two developmental pediatricians with use of a modified version of the
      Clinical Adaptive Test/Clinical Linguistic Auditory Milestone Scale, a measure of
      visual-motor and language abilities. RESULTS: The mean cognitive developmental
      quotient for subjects with absent to mild ventriculomegaly was 90.3 (range 54 to
      120, SD 17.4), whereas the mean cognitive developmental quotient for those with
      moderate to severe ventriculomegaly was 74.0 (range 65 to 100, SD 17.1) (p <
      0.01). There was a negative correlation between the degree of ventriculomegaly
      and the cognitive developmental quotient (r = -0.43, p < 0.025) and a positive
      correlation between the level of the lesion and the cognitive developmental
      quotient (r = 0.50, p < 0.01). CONCLUSIONS: The degree of ventriculomegaly
      determined on high-resolution prenatal ultrasonography is predictive of early
      cognitive development in children with myelomeningocele, with worsening
      ventriculomegaly being associated with lower cognitive developmental quotients.
      The anatomic level of the lesion also has predictive value, with lower level
      lesions being associated with more favorable cognitive outcomes. However, because
      of the high degree of variance in developmental quotients within the two
      ventriculomegaly groups, we advise clinicians to use caution in the
      interpretation and use of our data.

PMID- 9290447
TI  - The role of p53 tumor suppressor gene and bcl-2 protooncogene in rat corpus
      luteum death.
AB  - OBJECTIVE: The purpose of this study was to find out whether the mammalian corpus
      luteum undergoes genetically programmed cell death as evidenced by the positive
      or negative expression of specific biochemical markers of apoptosis (p53 and bcl
      2). STUDY DESIGN: Twenty-six immature 28-day-old female Sprague-Dawley rats were
      given 10 IU of pregnant mare's serum gonadotropin to induce ovulation and corpus
      luteum formation. Corpora lutea were collected on postovulatory days 8, 10, 12,
      and 14 and snap-frozen immediately. Determinations of apoptotic fragmentation of
      deoxyribonucleic acid were performed with use of samples radiolabeled at 3'-ends
      with deoxynucleotide alpha-phosphorus 32-deoxycytidine triphosphate (3000
      Ci/mmol). Transcription of p53 and bcl-2 was determined by Northern blot analysis
      of total ribonucleic acid. Protein expression of p53 and bcl-2 was determined by
      Western blot analysis with a monoclonal rat antibody for p53 and a polyclonal
      rabbit antibody for bcl-2. RESULTS: The nuclear fragmentation assay revealed
      formation of oligonucleosomes resulting in typical laddering of the
      deoxyribonucleic acid (corpus luteum) consistent with programmed cell death.
      Northern blot analysis of total ribonucleic acid prepared from immature (28-day
      old) rat corpus luteum revealed the presence of a single p53 messenger
      ribonucleic acid transcript (2.1 kb) in all ages of corpus luteum studied from
      day 8 to day 14. Western blot analysis for p53 revealed a gradual reduction in
      p53 protein in corpus luteum from day 8 to day 12 until it became undetectable on
      day 14. Western blotting revealed expression of specific protein for bcl-2.
      CONCLUSIONS: It appears that programmed cell death, as evidenced by formation of
      oligonucleosomes, occurs during mammalian luteal regression. The patterns of p53
      ribonucleic acid expression in the corpus luteum suggest that the protein
      products of p53 and bcl-2 do not act in a diametric manner to regulate programmed
      cell death in the corpus luteum. The current results suggest that the mechanisms
      leading to programmed cell death in the mammalian corpus luteum may differ
      considerably from those in other organ systems.

PMID- 9290448
TI  - The Preterm Prediction Study: association of cesarean delivery with increases in
      maternal weight and body mass index.
AB  - OBJECTIVE: Our purpose was to evaluate whether maternal weight and body mass
      index measured either before or during pregnancy are associated with an increased
      risk of cesarean delivery. STUDY DESIGN: Maternal weight and height were
      prospectively collected on 2929 women in the National Institutes of Health
      Maternal-Fetal Medicine Units Network Preterm Prediction Study. Prepregnancy and
      27- to 31-week maternal weight and height were used to calculate the body mass
      index, and its contribution to the risk of cesarean delivery was determined.
      Women with prenatally diagnosed congenital anomalies (n = 89) and pregestational
      diabetes (n = 31) were excluded from analysis. RESULTS: Univariate analysis of
      risk factors for cesarean delivery in the 2809 eligible women revealed a
      decreased risk of cesarean delivery with maternal age < 18 years and multiparity;
      increased risk of cesarean delivery was noted with maternal age > 35 years and a
      male fetus. Increases in either prepregnancy or 27- to 31-week maternal weight (5
      pound units) or body mass index (1.0 kg/m2 units) were significantly associated
      with an increased odds of cesarean delivery (p = 0.0001). Each unit increase in
      prepregnancy or 27- to 31-week body mass index resulted in a parallel increase in
      the odds of cesarean delivery of 7.0% and 7.8%, respectively. Multivariable
      stepwise logistic regression analysis confirmed the association of male fetus,
      age, nulliparity, and body mass index as significant variables contributing to
      cesarean delivery risk. CONCLUSIONS: The risk of cesarean delivery is associated
      with incremental changes in maternal weight and body mass index before and during
      pregnancy after adjustment for potential confounding factors. Prepregnancy
      counseling about optimizing maternal weight and monitoring weight gain during
      pregnancy to decrease the risk of cesarean delivery are supported by this study.

PMID- 9290449
TI  - Twin-to-twin transfusion syndrome: aggressive therapeutic amniocentesis.
AB  - OBJECTIVE: Untreated twin-to-twin transfusion syndrome reportedly carries nearly
      a 100% mortality rate. Over the last decade a number of therapeutic modalities
      have been attempted, including aggressive amniocentesis. This study was a
      retrospective evaluation of a series of 22 patients with twin-to-twin transfusion
      syndrome referred to our prenatal diagnostic center to determine the
      effectiveness in treating twin-to-twin transfusion syndrome with aggressive
      therapeutic amniocentesis. STUDY DESIGN: In this study three patients did not
      meet diagnostic criteria. For various reasons six patients did not have
      therapeutic amniocentesis done. One patient chose to terminate the pregnancy
      after three amniocenteses. Another patient chose to discontinue therapy after
      removal of just 100 ml of amniotic fluid. Of the 11 treated patients, the mean
      gestational age at diagnosis was 22 weeks 4 days (range 15 weeks 4 days to 26
      weeks 4 days). RESULTS: The mean number of amniocenteses done was 5.5 (range 1 to
      12). The mean total of amniotic fluid removed over the course of the pregnancy
      was 8.0 L (range 1100 to 24,200 ml). The mean number of days gained in these
      pregnancies was 56 (range 9 to 125) compared with 54 days for the untreated
      women. Eighty-two percent of the treated fetuses survived compared with 50% in
      the untreated group. Newborns in the treated group were delivered at a later
      gestational age and weighed more than those in the untreated group. CONCLUSIONS:
      Spontaneous resolution of twin-to-twin transfusion syndrome does occur.
      Therapeutic amniocentesis offers a simple, effective method of therapy for twin
      to-twin transfusion syndrome.

PMID- 9290450
TI  - Multiple pregnancy rate and embryo number transferred during in vitro
      fertilization.
AB  - OBJECTIVE: Our goal was to achieve a good pregnancy rate after in vitro
      fertilization; more than one embryo, if available, is transferred to the uterine
      cavity. This is a recognition of the low implantation rates of embryos from in
      vitro fertilization. A consequence of this can be high-order multiple
      implantation with obstetric complications. STUDY DESIGN: Retrospectively, we
      reviewed 42 months' in vitro fertilization experience; we related the number of
      embryos transferred and the pregnancy outcome. During this period 2173 fresh and
      frozen-thawed embryo transfers were performed. One to six embryos were
      transferred to women whose average age was 34.4 years (range 21 to 49). RESULTS:
      A total of 734 delivered pregnancies (33.8% per embryo transfer) was analyzed
      according to whether they were single or multiple, and this was related to the
      original number of embryos transferred. The overall multiple pregnancy rate was
      31.3% (24.7% twins, 5.8% triplets, 0.8% quadruplets). CONCLUSIONS: There was a
      trend toward a higher pregnancy rate with more embryos transferred. The embryonic
      implantation rate, which reflects the number of embryos that implant per total
      transferred, was not significantly different in any one group, except in older
      women in whom more than one embryo was transferred. Whereas greater numbers of
      embryos (more than three) were transferred in couples with a poorer prognosis for
      successful in vitro fertilization (e.g., older women [> 36 years old], previous
      failure of in vitro fertilization, poor embryo quality, or severe male factor
      causing infertility), there still remained a significant trend toward a higher
      pregnancy rate when more embryos were transferred. The embryonic implantation
      rate did not decline in the poorer-prognosis groups (more than three embryos
      transferred), yet the multiple pregnancy rate was increased. Technologic
      procedures such as embryo biopsy for aneuploidy screening are proposed as one
      means to reduce embryo numbers transferred without decreasing the overall
      pregnancy rate.

PMID- 9290451
TI  - Coculture of human embryos with buffalo rat liver cells for women with decreased
      prognosis in in vitro fertilization.
AB  - OBJECTIVE: The coculture of human embryos with epithelial cells may improve both
      embryo quality and pregnancy rates. In this current study we tested the efficacy
      of coculture with the buffalo rat liver cell line on pregnancy rates in women
      with a potentially poor prognosis for success with in vitro fertilization
      (previous in vitro fertilization failure, advanced maternal age, increased early
      follicular follicle-stimulating hormone levels, and anovulation). STUDY DESIGN:
      This prospective controlled study evaluated a total of 203 women (135 coculture,
      68 controls) undergoing in vitro fertilization. Implantation rates per embryo,
      clinical pregnancy rates, and continuing/delivered pregnancy rates were analyzed.
      RESULTS: Buffalo rat liver cells, which are commercially available, are stable in
      coculture. Implantation rates (number of sacs with fetal heart motion per embryos
      transferred) were similar for coculture (19%) and control (18%) embryos. No
      difference in the rate of continuing/delivered pregnancies per retrieval was
      noted (17% coculture vs 14% control) in the group with advanced maternal age, but
      coculture caused a trend toward improved pregnancy rates in the group with
      ovulatory dysfunction (43% coculture vs 14% control) and the group with previous
      in vitro fertilization failure (34% coculture vs 28% control). CONCLUSION: This
      is the first published controlled study to our knowledge that reports the use of
      the buffalo rat liver cell coculture for human in vitro fertilization in a large
      number of patients. Our data support consideration of buffalo rat liver coculture
      for in vitro fertilization for women with previous in vitro fertilization failure
      and possibly for patients with oocyte or ovulatory dysfunction.

PMID- 9290452
TI  - Randomized trial of two doses of the prostaglandin E1 analog misoprostol for
      labor induction.
AB  - OBJECTIVE: Our purpose was to compare the safety and effectiveness of
      intravaginally administered misoprostol at doses of 25 micrograms and 50
      micrograms for indicated labor induction in patients with an unfavorable cervix.
      STUDY DESIGN: Three hundred ninety-nine patients received either 25 micrograms or
      50 micrograms of misoprostol, placed intravaginally in the posterior fornix, in
      this randomized double-blind trial. The dose was repeated every 3 hours until
      adequate labor was achieved (at least three contractions in 10 minutes). RESULTS:
      Among 399 patients evaluated, 192 patients were allocated to the 25 micrograms
      group and 207 patients to the 50 micrograms group. The start-to-delivery interval
      was shorter in the 50 micrograms group (826 minutes vs 970 minutes, p = 0.02).
      The incidence of vaginal delivery after one dose was higher in the 50 micrograms
      group (38.2% vs 25.0%, p = 0.007). Patients receiving 25 micrograms required
      oxytocin augmentation more frequently than did those receiving 50 micrograms
      (27.1% vs 16.9%, p = 0.02). No differences were noted in the cesarean or other
      operative delivery rates among patients in the two treatment groups. The
      incidence of newborns with a cord pH < 7.16 was greater in the 50 micrograms
      group (13.0% vs 6.8%, p = 0.04). Although the incidence of hyperstimulation was
      similar between the groups, the incidence of tachysystole was higher in the 50
      micrograms group (32.8% vs 15.6%, p = 0.0001). CONCLUSIONS: Although a dose of 50
      micrograms is associated with a shorter start-to-delivery interval and a higher
      incidence of vaginal delivery after one dose, 25 micrograms of intravaginal
      misoprostol is effective and associated with a lower incidence of tachysystole
      and cord pH values < 7.16.

PMID- 9290453
TI  - Radical hysterectomy: current management guidelines.
AB  - Over the past 11 years (January 1985 through December 1996) the senior authors
      (B.F.H. and H.B.K.) have performed 205 radical hysterectomies. The most notable
      trend observed was a marked decrease in length of stay from 12.8 days to 3.5
      days. Contributing factors include use of the Maylard incision, placement of
      suprapubic Foley catheters, discontinuation of drains, early oral feeding,
      admission to the hospital on the day of surgery, and initiation of a critical
      care pathway. All criteria for short-stay radical hysterectomy were established
      by 1994. With continued modification of surgical technique and use of the
      critical care pathway, short stay has become our standard of care for radical
      hysterectomy. Complications are minimal, with neither long-term morbidity nor
      mortality associated with the short stay. In addition, significant cost savings
      occur, which benefits the patient, hospital, and the health care system.

PMID- 9290454
TI  - Use of antibiotics to prevent preterm birth.
AB  - Our purpose is to review recent data and provide a clinical opinion on the use of
      antibiotics to prevent preterm birth or related maternal-neonatal complications.
      A literature review and a synthesis of opinion are provided. During prenatal
      care, standard practices should be applied regarding Neisseria gonorrhoeae,
      Chlamydia trachomatis, and bacteriuria. In addition, screen for and treat
      bacterial vaginosis in patients at high risk for preterm birth but do not treat
      Ureaplasma urealyticum or group B streptococci genital colonization. With preterm
      labor and intact membranes, standard practices should be applied regarding group
      B streptococci prophylaxis. Do not give antibiotics routinely to prolong
      pregnancy, but in patients with bacterial vaginosis and Trichomonas vaginalis
      specific treatment should be given. With preterm premature rupture of membranes,
      standard practices should be applied regarding group B streptococci prophylaxis,
      but additional antibiotics should also be given to prolong pregnancies at 24 to
      32 weeks' gestation. Reported adverse effects have been few to date. However,
      increased diligence is needed for resistant organisms. In selected clinical
      settings antibiotic therapy is now indicated to prolong pregnancy and prevent
      maternal-neonatal complications associated with preterm birth.

PMID- 9290455
TI  - Low rates of hormone replacement in visits to United States primary care
      physicians.
AB  - Our objective was to determine national rates and predictors of hormone
      replacement therapy. We analyzed a nationally representative sample of 6341
      office visits by women aged > or = 40 years to primary care physicians in the
      1993 and 1994 National Ambulatory Medical Care Surveys. Independent predictors of
      estrogen use were determined by logistic regression. Time trends from 1989
      through 1994 also were evaluated. Hormone replacement therapy was documented in
      4.7% of visits in 1989 to 1990 and 8.0% in 1993 to 1994. In 1993 to 1994 women
      with menopausal symptoms were six times more likely to have hormone replacement
      reported. In the absence of symptoms, obstetrician-gynecologists were nearly four
      times as likely to report hormone replacement therapy. Age 50 to 59 years, white
      race, osteoporosis, hyperlipidemia, and residence in the West and in
      nonmetropolitan areas also independently-predicted hormone replacement. Low rates
      of estrogen therapy by non-obstetrician-gynecologists and substantial practice
      variations suggest missed opportunities for hormone replacement therapy.

PMID- 9290456
TI  - Potential value of fetal echocardiography in the differential diagnosis of twin
      pregnancy with presence of polyhydramnios-oligohydramnios syndrome.
AB  - OBJECTIVE: Our purpose was to establish whether index values of cardiac
      performance could discriminate between the twin-twin transfusion syndrome and
      placental insufficiency as the etiology of the polyhydramnios-oligohydramnios
      sequence in monochorionic diamniotic twins. STUDY DESIGN: Thirteen monochorionic
      diamniotic twin pregnancies with ultrasonographic evidence of polyhydramnios
      oligohydramnios sequence had a complete echocardiography. The etiology was
      confirmed postnatally: placental insufficiency in eight pairs and the twin-twin
      transfusion syndrome in five. Intertwin comparisons were made for the following
      cardiac parameters: cardiothoracic index, end-diastolic thickness of the
      ventricular walls and septum, aortic and pulmonary artery Doppler peak
      velocities, ejection and acceleration times, left ventricular shortening
      fraction, and combined cardiac output and output indexed to fetal weight.
      RESULTS: All five recipient twins had thickened ventricular walls. The left
      ventricular shortening fractions and outputs were significantly increased in the
      donor twin with twin-twin transfusion syndrome and normal in placental
      insufficiency. CONCLUSION: In twin-twin transfusion syndrome the donor twin shows
      evidence of a hyperdynamic cardiac state. Intertwin comparison of cardiac
      parameters, especially the left ventricular shortening fraction, can be
      considered a useful tool in diagnosing the different etiologies of the
      polyhydramnios-oligohydraminos sequence.

PMID- 9290457
TI  - Plasma adenosine responses during repeated episodes of umbilical cord occlusion.
AB  - OBJECTIVE: The purpose of this study was to measure changes in adenosine
      concentration in fetal arterial blood with use of an animal model of intermittent
      cord occlusion. Adenosine has been shown to be a potent vasodilator and inhibitor
      of metabolic processes in the adult, actions that help maintain a balance between
      oxygen supply and oxygen use. STUDY DESIGN: After a 30-minute control period,
      five chronically instrumented fetal sheep (125 +/- 2.2 days' gestation) were
      subjected to a 1-minute cord occlusion, followed by a 2-minute recovery. The
      occlusion-release cycle was repeated 20 times. Then, after a 1-hour interim, the
      same 20 cycles of occlusion were repeated. Fetal blood was collected during cord
      occlusion and 30 seconds after release. RESULTS: The plasma adenosine
      concentration averaged 0.82 +/- 0.19 mumol/L during the initial control period.
      The plasma adenosine concentration increased significantly to 1.06 +/- 0.23
      mumol/L and 1.19 +/- 0.20 mumol/L during and after the fifth occlusion (p < 0.05
      and 0.01, respectively). The plasma adenosine concentration reached a maximal
      level of 1.31 +/- 0.28 mumol/L after the twentieth cord occlusion. The
      concentration during the second group of occlusions was also higher than that
      during the control period (p < 0.05) but not higher than that during the first
      recovery period. By the conclusion of the study the plasma adenosine
      concentration had returned to 0.70 +/- 0.16 mumol/L. CONCLUSIONS: Plasma
      adenosine increases cyclically with intermittent cord occlusion in the near-term
      fetal sheep, but the response is attenuated or lost after 2 hours. These results
      together with those of earlier studies are consistent with a hypoxic protective
      action of adenosine that is largely restricted to early time periods of
      continuing intermittent hypoxia.

PMID- 9290458
TI  - Fetal carriers of the factor V Leiden mutation are prone to miscarriage and
      placental infarction.
AB  - OBJECTIVES: The factor V Leiden mutation is the most common genetic
      predisposition to thrombosis. However, little is known concerning the
      reproductive outcome of mutation carriers or prenatal expressivity of this
      thrombogenic mutation. Our purpose was to examine whether this mutation presents
      phenotypically as miscarriage or idiopathic placental thrombosis. STUDY DESIGN:
      We performed two studies. First, a case-control comparison to determine whether
      fetal or maternal carriers of the factor V Leiden mutation are at risk for
      spontaneous miscarriage was performed, and, second, a cohort study evaluating
      placental infarction in fetuses carrying this mutation was performed. RESULTS: We
      found a twofold increase in the factor V Leiden carrier frequency in 12 of 139
      (8.6%) abortuses compared with 17 of 403 (4.2%) unselected pregnant women seen in
      the labor and delivery suite and, even more remarkable, a tenfold increase in the
      fetal carrier frequency in 10 of 24 (42%) placentas with > 10% placental
      infarction compared with 7 of 372 (1.9%) placentas with < 10% placental
      infarction. CONCLUSIONS: These findings suggest a prenatal phenotype and effects
      of this mutation at the fetoplacental interface. If large prospective studies
      confirm these findings, then testing for this thrombogenic mutation should be
      considered in women and placental tissue from spontaneous abortuses and placentas
      with evidence of placental infarction. In addition to identifying individuals and
      families at risk for thrombosis, this information may help to improve our
      understanding of hemostasis and circulatory disturbances at the fetoplacental
      interface.

PMID- 9290459
TI  - High expression of tumor necrosis factor-alpha and interleukin-6 in
      periventricular leukomalacia.
AB  - OBJECTIVE: Periventricular leukomalacia, a common neonatal brain white matter
      lesion, is a major risk factor for cerebral palsy. Subclinical chorioamnionitis
      is a risk factor for the development of periventricular leukomalacia, and
      inflammatory cytokines have been implicated as central mediators of brain injury
      in this disorder. To elucidate the relationship between the local expression of
      cytokines and periventricular leukomalacia, we studied neonatal brains to
      determine whether high expression of tumor necrosis factor-alpha, interleukin-1
      beta, and interleukin-6 was observed in these lesions. STUDY DESIGN:
      Immunohistochemical staining for cytokines (tumor necrosis factor-alpha,
      interleukin-1 beta, and interleukin-6) was performed in 10% formalin-fixed,
      paraffin-embedded brain sections of 17 cases with periventricular leukomalacia.
      Specimens were obtained from autopsies performed between 1987 and 1994. Brain
      sections from 17 cases of neonatal deaths without periventricular leukomalacia
      lesions matched for gestational age at birth, duration of postnatal survival, and
      presence or absence of infection-related morbidity were used as controls.
      RESULTS: The expression of tumor necrosis factor-alpha, interleukin-1 beta, or
      interleukin-6 was demonstrated in 88% (15/17) of cases with and in 18% (3/17) of
      cases without periventricular leukomalacia (p < 0.001). Cytokines were expressed
      mainly in hypertrophic astrocytes and microglial cells. The expression of tumor
      necrosis factor-alpha, interleukin-1 beta, and interleukin-6 was identified in
      82% (14/17), 29% (5/17), and 71% (12/17) of cases of periventricular
      leukomalacia, respectively. However, a significantly lower proportion of cases
      without periventricular leukomalacia expressed tumor necrosis factor-alpha (18%,
      3/17) and interleukin-6 (6%, 1/17) than those with the disorder (p < 0.005 for
      each). CONCLUSIONS: Expression of tumor necrosis factor-alpha and interleukin-6
      was observed more frequently in brain lesions with periventricular leukomalacia
      than in those without periventricular leukomalacia. These findings provide strong
      support for the hypothesis that proinflammatory cytokines play a role in the
      genesis of periventricular leukomalacia.

PMID- 9290460
TI  - Better postural balance in elderly women receiving estrogens.
AB  - OBJECTIVE: The amount of bone mass and the tendency to fall are main risk factors
      for hip fractures and both deteriorate with advancing age. The dynamics between
      estrogen exposure and fracture protection seem too rapid to be explained by an
      effect on bone mass only. Postural balance function may be another potential
      mechanism for the fracture-protecting effect of estrogens. STUDY DESIGN: We
      examined 16 long-term users of 17 beta-estradiol implants (20 mg) (mean age 67.9
      years and mean duration of treatment 17.3 years [3.3 to 34 years]) and 16 age
      matched (+/-2 years) nonusers (mean age 68.3 years). Postural balance (sway
      velocity) was measured by static posturography before and after blindfolding and
      application of vibration stimulus (20 to 100 Hz) to the calf muscles to disturb
      the proprioception and to induce imbalance. RESULTS: Sway velocities were
      significantly lower in estrogen users than in nonusers (p = 0.0067) and similar
      to those in young premenopausal women. The differences were accentuated after
      provocation by blindfolding and by increasing frequencies of vibration stimulus
      to the calf muscle. Serum levels of estradiol and estradiol/sex hormone-binding
      globulin were negatively and follicle-stimulating hormone levels positively
      associated with sway velocity (p = 0.0194, p = 0.0036, and p = 0.0052,
      respectively) and independent of age (p = 0.02 to 0.005), supporting causality
      between estrogen exposure and postural balance. CONCLUSIONS: These data indicate
      that postural balance function is better preserved in long-term estrogen users
      than in nonusers. Effects on postural balance function may be one mechanism
      explaining the rapid increase in distal forearm fractures early after menopause
      and the rapid dynamics between estrogen exposure and hip fracture protection and
      may potentially reduce the fracture risk in elderly women starting estrogen
      replacement therapy in spite of marginal increases in bone mass.

PMID- 9290461
TI  - Enhanced deoxyribonucleic acid damage and repair but unchanged apoptosis in
      uterine leiomyomas treated with gonadotropin-releasing hormone agonist.
AB  - OBJECTIVE: Our purpose was to investigate the histopathologic changes in uterine
      leiomyomas in cell proliferation, proliferating cell nuclear antigen expression,
      angiogenesis, and apoptosis after treatment with gonadotropin-releasing hormone
      agonist. STUDY DESIGN: Fifteen consecutive patients who had undergone
      gonadotropin-releasing hormone agonist treatment before surgery and 44 patients
      who did not were studied. The volumes of myomas were determined
      ultrasonographically, and in patients receiving gonadotropin-releasing hormone
      agonist therapy measurements were done again after administration of the
      gonadotropin-releasing hormone agonist to evaluate the response to treatment.
      Paraffin sections were stained with hematoxylin and eosin, PC 10 for
      proliferating cell nuclear antigen expression, MIB 1 for measurement of cell
      proliferation, ApopTag for apoptosis, and factor VIII for quantitation of
      microvessel density. A deoxyribonucleic acid fragmentation test was also done on
      nine cases with available frozen tissues. RESULTS: Most of the leiomyomas showed
      substantial expression of proliferating cell nuclear antigen. Gonadotropin
      releasing hormone agonist therapy further induced significant overexpression of
      proliferating cell nuclear antigen (p = 0.0004, chi 2 test). All three leiomyomas
      that failed to respond to therapy showed less proliferating cell nuclear antigen
      staining compared with the good responders. In contrast, data from MIB 1
      immunostaining showed that < 0.3% of leiomyoma cells were proliferating. However,
      positive-staining cells were more frequently detected in the treatment group
      (0.075% +/- 0.091% vs 0.002% +/- 0.010%, p = 0.0002, Mann-Whitney U test).
      Apoptosis developed spontaneously in leiomyoma cells independent of gonadotropin
      releasing hormone agonist therapy. No significant change in apoptosis but a
      significant increase in microvessel density was observed in the treatment group
      compared with the control group. CONCLUSION: Enhanced deoxyribonucleic acid
      damage or repair with cell growth arrest may be responsible for the action of
      gonadotropin-releasing hormone agonist in shrinking uterine leiomyomas. Moreover,
      the extent of proliferating cell nuclear antigen expression seems to be
      associated with the response to gonadotropin-releasing hormone agonist therapy.

PMID- 9290462
TI  - Women with sickle cell trait are at increased risk for preeclampsia.
AB  - OBJECTIVE: Our purpose was to determine the rate of preeclampsia in women who are
      positive for sickle cell trait. STUDY DESIGN: All African-American women were
      tested for sickle cell trait with the "sickledex" screen at the fist prenatal
      visit and prospectively enrolled in this study from March 1994 to June 1995.
      "Sickledex" screens were confirmed with hemoglobin electrophoresis. Demographic
      data were collected at the time of enrollment. Outcome data, including
      preeclampsia (as defined by The American College of Obstetricians and
      Gynecologists criteria), gestational age at delivery, birth weight, and
      postpartum endometritis were collected immediately post partum. Assuming a 10%
      rate of positive sickle cell trait, 1100 patients were required to demonstrate a
      doubling in the rate of preeclampsia with 80% power and p < 0.05. The Student t
      test, the Mann-Whitney U test, chi 2 analysis, and Fisher's exact tests were used
      for statistical analysis. RESULTS: Of 1584 women enrolled in the study, 162 were
      positive for sickle cell trait. Sickle cell trait-positive women were older than
      the sickle cell trait-negative women (24.4 +/- 4.6 vs 23.0 +/- 4.4 years, p <
      0.001), but there was no significant difference in parity. The rate of
      preeclampsia was significantly increased in sickle cell-positive women (24.7% vs
      10.3%, p < 0.0001). There was no significant difference in the rate of chronic
      hypertension, diabetes, or smoking. Parous sickle cell-positive women more
      frequently gave a history of preeclampsia in a previous pregnancy (21.4% vs 9.3%,
      p < 0.0001). There was a statistically significant decrease in gestational age at
      delivery and birth weight in sickle cell trait-positive women (36.7 +/- 2.7 vs
      37.7 +/- 3.0 weeks, p < 0.0001; and 3082 +/- 591 vs 3369 +/- 573 gm, p < 0.0001).
      The rate of postpartum endometritis was significantly increased in the women
      positive for sickle cell trait (12.3% vs 5.1%, p < 0.001), although both groups
      had a similar cesarean section rate (14.8% vs 12.6%, not significant).
      CONCLUSION: This is the first prospective study to demonstrate that sickle cell
      trait-positive women are at significantly higher risk for development of
      perinatal complications that have traditionally been associated with sickle
      disease.

PMID- 9290463
TI  - Plasma endothelin-1 and tumor necrosis factor-alpha concentrations in pregnant
      and cyclic rats after low-dose endotoxin infusion.
AB  - Plasma endothelin-1 and tumor necrosis factor-alpha were determined in pregnant
      and cyclic rats after infusion of either endotoxin (1.0 microgram/kg of body
      weight) or saline solution. After endotoxin, but not after saline solution,
      administration there was a transient endothelin-1 response in pregnant rats but
      not cyclic rats. In both reproductive conditions there was an equally high
      transient tumor necrosis factor-alpha response after endotoxin.

PMID- 9290464
TI  - Effect of antenatal thyrotropin-releasing hormone on uterine contractility, blood
      pressure, and maternal heart rate.
AB  - OBJECTIVE: The goal was to study the effects on uterine contractility, blood
      pressure, and heart rate of thyrotropin-releasing hormone given antenatally in
      combination with glucocorticoids to accelerate fetal maturation. STUDY DESIGN: A
      placebo-controlled, randomized, double-blind study was performed involving 30
      women whose pregnancies were followed up at the University Hospital Gasthuisberg
      in 1994 and 1995. RESULTS: Thyrotropin-releasing hormone induced a significant
      mean increase of nearly 6 mm Hg in systolic blood pressure and approximately 5 mm
      Hg in diastolic blood pressure. The duration of this raise was < 20 minutes.
      Thyrotropin-releasing hormone had no significant effect on maternal heart rate or
      uterine contractility: 4.2 +/- 1.6 contractions per hour before versus 4.7 +/-
      1.7 contractions per hour after treatment. CONCLUSIONS: Thyrotropin-releasing
      hormone induces a small (mean < 6 mm Hg) and brief mean (< 20 minutes) increase
      in blood pressure but appears to have no clinically detectable effect on uterine
      contractility.

PMID- 9290465
TI  - Can flow cytometric detection of platelet activation early in pregnancy predict
      the occurrence of preeclampsia? A prospective study.
AB  - OBJECTIVES: An increased platelet activation status is present in patients with
      preeclampsia. Our purpose was (1) to establish by means of flow cytometry whether
      platelets circulate in an activated state during the first and second trimesters
      of pregnancy and (2) to establish whether early platelet activation predicts the
      onset of preeclampsia. STUDY DESIGN: Consecutively, 244 pregnant women were
      included in a prospective study design. Platelets in whole blood samples from the
      pregnant women in the first trimester, the second trimester, and after delivery
      were labeled with the following antibodies associated with platelet activation:
      anti-CD62P (P-selectin, alpha-granule secretion), anti-CD63 (GP53, lysosomal
      secretion), anti-CD31 (GPIIa', platelet endothelial cell adhesion molecule-1).
      The surface antigen exposure was determined by double-label flow cytometry with
      anti-CD42b (GPIb, a platelet-specific monoclonal glycoprotein) to select
      platelets and platelet-derived materials. Preeclampsia was defined as a diastolic
      blood pressure > or = 90 mm Hg and proteinuria > or = 0.3 gm in a 24-hour urine
      sample (International Society for Study of Hypertension in Pregnancy criteria).
      RESULTS: Seventeen of 244 patients had preeclampsia (6.9%). Only first-trimester
      CD63 expression had an area under the curve > 0.5 by receiver-operator
      characteristic curve analysis and was selected as a possible predictor of
      preeclampsia. We found a sensitivity of 47% and a specificity of 76% with use of
      a percentage of activated platelets above 2% as a positive test. Likelihood
      ratios were 1.94 for positive likelihood and 0.69 for negative likelihood.
      Univariate logistic regression analysis results were odds ratio 2.8 (95%
      confidence interval 1.0 to 7.6). Multivariate logistic regression analysis
      results were odds ratio 2.9 (95% confidence interval 0.92 to 8.9). However, the
      odds ratio of first antenatal diastolic blood pressure was two to four times
      higher than the odds ratio of first-trimester CD63 expression. The combination of
      first-trimester CD63 and first antenatal diastolic blood pressure increases the
      positive likelihood ratio from 1.94 to 9.4, with a sensitivity of 41%, a
      specificity of 96%, and a negative likelihood ratio of 0.62. CONCLUSIONS:
      Increased first-trimester CD63 expression is an independent risk factor for
      development of preeclampsia. CD63 expression might be useful to identify a
      subgroup of patients with a high risk for development of preeclampsia, especially
      in combination with first-trimester antenatal diastolic blood pressure. This
      method of patient selection may enable more efficient intervention studies in
      patients at risk than do the selection methods used so far.

PMID- 9290467
TI  - Herpes simplex virus seropositivity and reactivation at delivery among pregnant
      women infected with human immunodeficiency virus-1.
AB  - OBJECTIVE: Our purpose was to determine whether pregnant women infected with
      human immunodeficiency virus-1 have an increased risk of herpes simplex virus-2
      seropositivity and herpes simplex virus reactivation at delivery. STUDY DESIGN:
      Sixty women infected with human immunodeficiency virus and 8408 other patients
      who were delivered at the University of Washington between 1989 and 1995 had
      herpes simplex virus serologic determinations at delivery. Genital herpes simplex
      virus cultures were obtained for 48 (80%) of the human immunodeficiency virus
      infected women and 5567 (66%) of the controls. Logistic regression was used to
      adjust for possible confounding factors. RESULTS: Forty-five (75%) of human
      immunodeficiency virus-infected women and 2709 (32%) controls were seropositive
      for herpes simplex virus-2 (p < 0.0001). Eight percent of human immunodeficiency
      virus-infected women and 2% of controls had herpes simplex virus reactivation in
      labor (p < 0.05). CONCLUSIONS: Infection with herpes simplex virus-2 is common
      among pregnant women infected with human immunodeficiency virus. Herpes simplex
      virus reactivation complicates labor in this group more often than in other
      obstetric patients. The role of herpes simplex virus in perinatal human
      immunodeficiency virus transmission warrants further study.

PMID- 9290466
TI  - Circulating endothelial cell adhesion molecules as diagnostic markers for the
      early identification of pregnant women at risk for development of preeclampsia.
AB  - OBJECTIVE: The aim of the current study was to determine levels of circulating
      endothelial cell adhesion molecules during preeclampsia and to assess their
      predictive value as diagnostic markers for the early identification of pregnant
      women at risk of developing preeclampsia. STUDY DESIGN: Plasma samples were
      obtained from women with preeclampsia; the syndrome of hemolysis, elevated liver
      enzymes, and low platelets; uncomplicated pregnancy-induced hypertension; and
      women with normal pregnancy. In addition, longitudinal plasma profiles of
      pregnant women were randomly collected to determine individual profiles of
      circulating endothelial cell adhesion molecules. A sandwich enzyme-linked
      immunosorbent assay technique was used to quantitate concentrations of soluble
      intercellular adhesion molecule-1 (CD54), vascular cell adhesion molecule-1
      (CD106), E-selectin (CD62E), platelet endothelial cell adhesion molecule (CD31),
      and P-selectin (CD62P). RESULTS: Plasma levels of intercellular adhesion molecule
      1, vascular cell adhesion molecule-1, E-selectin, and platelet endothelial cell
      adhesion molecule-1 were significantly elevated in women with preeclampsia
      compared with healthy control pregnant women. Longitudinal analysis of soluble
      plasma intercellular adhesion molecule-1 and vascular cell adhesion molecule-1
      levels during pregnancy revealed that these molecules (1) show little variation
      in healthy pregnant women, (2) do not vary during normal pregnancy, and (3) are
      significantly elevated in women with preeclampsia and the syndrome of hemolysis,
      elevated liver enzymes, and low platelets compared with control pregnant women
      and those with uncomplicated pregnancy-induced hypertension. Analysis of soluble
      intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 levels in
      longitudinal profiles of pregnant women identified significantly elevated levels
      of these molecules in the plasma of preeclampsia-prone women 3 to 15 weeks before
      the onset of clinical symptoms. CONCLUSION: Elevated soluble intercellular
      adhesion molecule-1 and vascular cell adhesion molecule-1 measurements during
      pregnancy can be considered as major risk factors. Elevated levels of these
      substances in the plasma of pregnant women with preeclampsia support the concept
      of a primary endothelial cell involvement in the pathogenesis of preeclampsia.
      Although currently based on a limited database, significantly elevated levels of
      soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1
      in the plasma of otherwise healthy pregnant women suggest a very high predictive
      value of these molecules for the earliest identification of women at risk of
      developing preeclampsia.

PMID- 9290468
TI  - Increased incidence of preeclampsia in women conceiving by intrauterine
      insemination with donor versus partner sperm for treatment of primary
      infertility.
AB  - OBJECTIVE: Reports suggest that there is an increased incidence of preeclampsia
      after a previously normal pregnancy if there is a change in paternity. We
      hypothesize that there is a higher incidence of preeclampsia (proteinuric
      hypertension) in women conceiving by intrauterine insemination with donor sperm
      versus intrauterine insemination with partner sperm. STUDY DESIGN: This was a
      retrospective cohort study. In women with primary infertility all pregnancies
      achieved by either partner or donor intrauterine insemination carried to birth of
      a fetus (> 20 weeks) were identified. The medical records were examined for the
      maternal and pregnancy outcome data. The relative risk and 95% confidence
      interval were calculated for the risk of preeclampsia. The baseline data were
      compared with t tests, chi 2 analysis and Fisher's exact test where appropriate.
      RESULTS: Forty-four patients in the partner intrauterine insemination group and
      37 in the donor insemination group were identified as having primary infertility.
      Three cases of mild preeclampsia were found in the partner insemination program
      and nine cases of preeclampsia (five severe, four mild) in the donor insemination
      program (relative risk 1.85, 95% confidence interval 1.20 to 2.85). CONCLUSIONS:
      There is a higher incidence of preeclampsia in women conceiving by intrauterine
      insemination with washed donor sperm compared with intrauterine insemination with
      washed partner sperm. This supports, indirectly, an immunologic basis for
      preeclampsia. The antigenic factor would appear to be located on the sperm as
      opposed to the seminal fluid itself.

PMID- 9290469
TI  - Pregnancy complicated by congenital hepatic fibrosis with cavernous
      transformation of the portal vein: a case report.
AB  - A 24-year-old primigravid woman with cogenital hepatic fibrosis associated with
      cavernous transformation of the portal vein is described. Although the neonate
      could not survive because of the ileal atresia, the pregnancy and delivery did
      not pose a significant threat to the mother.

PMID- 9290470
TI  - Pregnancy complicated by multiple endocrine neoplasia type IIA (Sipple's
      syndrome).
AB  - A patient with preexisting multiple endocrine neoplasia type IIA had normal 24
      hour urinary metanephrine and vanillylmandelic acid excretions before and during
      pregnancy. After a benign prenatal course, the patient had a term spontaneous
      vaginal delivery. Multiple endocrine neoplasia type IIA antedating pregnancy may
      be associated with a normal obstetric outcome in the absence of a
      phenochromocytoma.

PMID- 9290471
TI  - Catastrophic shoulder dystocia and emergency symphysiotomy.
AB  - We present three cases of shoulder dystocia unrelieved by standard maneuvers,
      including cephalic replacement. Symphysiotomy was performed in an effort to
      preserve fetal life. All three infants sustained severe neurologic injury and
      later died. Maternal morbidity including urinary incontinence was significant but
      responded to treatment. Symphysiotomy may be the only method of relieving some
      cases of shoulder dystocia, but its role remains unclear because of operator
      inexperience and maternal morbidity.

PMID- 9290472
TI  - Spinal cord surgery and galactorrhea: a case report.
AB  - We report the case of a 39-year-old nonpregnant woman with amenorrhea and
      galactorrhea after spinal cord surgery. Activation of the afferent neuroendocrine
      pathway is postulated to have occurred at surgery.

PMID- 9290473
TI  - Diagnostic dilemma with elevated level of alpha-fetoprotein in an undiagnosed
      twin pregnancy with a small discordant holoacardius acephalus.
AB  - We report a case of a patient who had highly elevated levels of alpha-fetoprotein
      when she was first examined and a positive acetylcholinesterase test result in
      amniotic fluid. Despite repeated ultrasonographic screening, pathologic findings
      were not detected and the holoacardius acephalus twin was not identified. After
      termination of pregnancy the histopathologic findings demonstrated a twin
      pregnancy with a holoacardius acephalus.

PMID- 9290475
TI  - Bilateral pleural effusion in the first trimester: a predictor of chromosomal
      abnormality and embryonic death?
AB  - We describe two cases of Turner's syndrome with transient bilateral pleural
      effusion demonstrated by transvaginal ultrasonography in the first trimester. Our
      cases suggest the necessity for close follow-up examination and possibly genetic
      counseling when pleural effusion is encountered during the first trimester.

PMID- 9290474
TI  - Idiopathic thrombocytopenic purpura in pregnancy treated with pulsed high-dose
      oral dexamethasone.
AB  - Idiopathic thrombocytopenic purpura in pregnancy is usually treated with
      prednisone or intravenous immune globulin. Because of the fetal risk, there are
      few good alternatives for women who do not respond. We report a case of
      refractory idiopathic thrombocytopenic purpura successfully treated with pulsed
      high-dose oral dexamethasone, which offered ease of administration, low cost, and
      low risk.

PMID- 9290476
TI  - Acute renal failure in the first trimester resulting from uterine leiomyomas.
AB  - A primigravid woman with multiple uterine leiomyomas was seen at 8 weeks'
      gestation with acute renal failure and hypertension. After placement of bilateral
      nephrostomy tubes, renal function improved and blood pressure normalized. The
      pregnancy was complicated by maternal abdominal discomfort, intrauterine growth
      restriction, and perinatal death. A myomectomy performed post partum revealed a
      24.4 pound pedunculated leiomyoma compressing the right kidney and liver. Large
      uterine leiomyomas may cause obstructive nephropathy and renal failure in
      pregnancy.

PMID- 9290477
TI  - Postpartum ultrasonographic diagnosis of inferior vena cava thrombus associated
      with ovarian vein thrombosis.
AB  - Postoperative ultrasonographic assessment as a result of unremitting fever after
      cesarean section depicted a large pedunculated thrombus within the inferior vena
      cava at the level of the right renal vein. Subsequent imaging studies revealed
      that this thrombus was the distal extension of right ovarian vein thrombosis into
      the inferior vena cava.

PMID- 9290478
TI  - Spontaneous ovarian hyperstimulation syndrome with pregnancy.
AB  - Only two cases of severe spontaneous ovarian hyperstimulation syndrome with
      pregnancy have been reported. We report the third one and the only one that was
      successfully managed conservatively throughout pregnancy.

PMID- 9290479
TI  - Recurrence of unclassifiable uterine cancer after modified laparoscopic
      hysterectomy with morcellation.
AB  - In a premenopausal patient with a 1-year history of abnormal bleeding
      laparoscopic supracervical hysterectomy in combination with vaginal intrafascial
      cylindriform enucleation of the cervix was performed. Histologic evaluation of
      the morcellated uterus was unremarkable. Five months later the patient was
      diagnosed with a pelvic mass consistent with an undifferentiated adenocarcinoma.
      Retrospective evaluation of the cored and morcellated hysterectomy specimen
      showed clusters of malignant cells that may have been detected by preoperative
      curettage.

PMID- 9290480
TI  - Beat-to-beat variability is important in diagnosing a compromised fetus.

PMID- 9290481
TI  - Physicians should not be allowed to enter into contractual agreements with
      managed care companies that do not meet basic ethical standards.

PMID- 9290482
TI  - False-negative results in polymerase chain reaction-based prenatal diagnosis from
      maternal blood.

PMID- 9290484
TI  - Plasma vitamin E in preeclampsia.

PMID- 9290483
TI  - Angiogenin: a marker for preterm delivery in midtrimester amniotic fluid.

PMID- 9290485
TI  - Fungal vaginitis caused by nonalbicans species.

PMID- 9290486
TI  - Thrombotic thrombocytopenic purpura in pregnancy: a multifaceted disease.

PMID- 9290487
TI  - Comment on outcome of in vitro fertilization and embryo transfer in women with
      congenital uterine malformations.

PMID- 9290488
TI  - Good Samaritan laws.

PMID- 9290490
TI  - Threading the needle: a method to assist in removing endocervical curettage
      specimens from Kevorkian curettes.

PMID- 9290489
TI  - Internet and medicine.

PMID- 9290491
TI  - Squirrel monkeys as animal models of pelvic relaxation.

PMID- 9290492
TI  - Human immunodeficiency virus-1 shedding in the genital tract of a female long
      term nonprogressor without detectable plasma human immunodeficiency virus
      ribonucleic acid.

PMID- 9290493
TI  - Multiple gestations from in vitro fertilization: successful implantation alone is
      not associated with subsequent preeclampsia.

PMID- 9290494
TI  - Cone size after carbon dioxide conization.

PMID- 9290495
TI  - About the efficacy of oral tocolytic therapy.

PMID- 9290496
TI  - Maternal serum human chorionic gonadotropin level at fifteen weeks as a predictor
      for preeclampsia?

PMID- 9290497
TI  - Head injury and risk of Alzheimer's disease by apolipoprotein E genotype.
AB  - Head injury and apolipoprotein E (APOE)-epsilon 4 (e4) genotype have each been
      associated with increased risk of Alzheimer's disease. If APOE-e4 affects
      neuronal viability and branching, and if response to head injury differs in e4
      patients, then the association between head injury and Alzheimer's disease may
      vary with the presence of the e4 allele. The authors examined this association in
      a case-control study conducted between 1987 and 1995 among enrollees of the Group
      Health Cooperative of Puget Sound, a health maintenance organization in Seattle,
      Washington. Proxy informants reported prior head injury with loss of
      consciousness for 32 of 349 patients with probable Alzheimer's disease and for 16
      of 342 control subjects of similar age and sex who had been randomly selected
      from the same population (odds ratio (OR) = 2.1, 95% confidence interval (CI) 1.1
      3.8). Elevated risk was observed among men (OR = 4.2, 95% CI 1.5-11.5) but not
      among women (OR = 1.1, 95% CI 0.5-2.6). No significant variation in the head
      injury-Alzheimer's disease risk relation by APOE-e4 genotype was found among 230
      cases and 309 controls (OR = 3.1 (95% CI 0.7-14.6) for persons with at least one
      e4 allele and OR = 2.0 (95% CI 0.8-5.2) for those without e4). Neither age,
      education, race, type of proxy informant, nor duration of relationship with the
      proxy confounded the association. Head injury with loss of consciousness,
      although uncommon in this sample, was associated with increased risk of
      Alzheimer's disease. APOE-e4 was an independent risk factor which neither
      modified nor confounded the association. Susceptibility to Alzheimer's disease as
      conferred by APOE-e4 does not appear to increase the risk associated with head
      injury.

PMID- 9290498
TI  - Epidemiology of idiopathic cardiomyopathies in children and adolescents. A
      nationwide study in Finland.
AB  - Although idiopathic cardiomyopathies are prognostically important and are a
      common indication for cardiac transplantation in all age groups, the incidence
      and age distribution of idiopathic cardiomyopathies in a well-defined pediatric
      population have been poorly characterized. A retrospective study was carried out
      in Finland in 1980-1991 to obtain information on the epidemiology of childhood
      cardiomyopathies. The medical records of all patients aged birth to 20 years with
      cardiomyopathy from the five university hospitals and 16 central hospitals
      covering the entire country were reviewed. Moreover, data on causes of death from
      the Finnish National Census Bureau were examined. Of the 808 potential cases
      screened, 118 infants, children, and adolescents, representing an average age
      specific population of 1.4 million, were definitely identified as having
      idiopathic cardiomyopathy. The average annual occurrence of new cases was 0.65
      per 100,000 population (95% confidence interval (CI) 0.53-0.79). If the 15 cases
      diagnosed only after death during the 12-year study period were included, the
      occurrence increased to 0.74 per 100,000 population per year. Fifty-six new cases
      of dilated cardiomyopathy and 40 new cases of hypertrophic cardiomyopathy were
      diagnosed during the study period, giving average annual occurrences of
      0.34/100,000/year (95% CI 0.26-0.44) and 0.24/100,000/year (95% CI 0.17-0.33) for
      new cases of dilated and hypertrophic cardiomyopathies, respectively. At the end
      of 1991, the prevalence of dilated cardiomyopathy was 2.6/100,000 (95% CI 1.8
      3.6) and that for hypertrophic cardiomyopathy was 2.9/100,000 (95% CI 2.0-4.0).
      The number of new cases of dilated cardiomyopathy per year increased over the
      study period, whereas the annual occurrence of hypertrophic cardiomyopathy
      remained relatively constant. Marked variability was seen in occurrence among the
      different age groups of children with dilated cardiomyopathy, suggesting that
      different pathophysiologic mechanisms, and possibly etiologies, may exist in
      different age groups.

PMID- 9290499
TI  - Severe obesity as an explanatory factor for the black/white difference in stage
      at diagnosis of breast cancer.
AB  - Black women with breast cancer are less likely than white women to be diagnosed
      while their disease is still at a localized stage. Racial differences in the
      prevalence of obesity in the United States have also been documented. This study
      was undertaken to determine the extent to which the observed racial difference in
      stage at diagnosis of breast cancer could be explained by racial differences in
      obesity, specifically severe obesity. This was a population-based, retrospective
      study of 145 black women and 177 white women in Connecticut who were diagnosed
      with breast cancer between January 1987 and March 1989. Severe obesity was
      associated with both race and stage at diagnosis: Black women were significantly
      more likely than white women to be severely obese (26% vs. 7%, respectively), and
      severe obesity was significantly associated with diagnosis at TNM stage II or
      greater (multivariate-adjusted odds ratio = 3.10, 95% confidence interval (CI)
      1.28-7.52). Adjustment for severe obesity in a logistic regression model reduced
      the risk of later stage at diagnosis in blacks relative to whites by 33%, from an
      odds ratio of 1.98 (95% CI 1.22-3.19) to one of 1.66 (95% CI 1.01-2.73). The
      higher prevalence of severe obesity among black women may play an important role
      in explaining their relative disadvantage in stage at diagnosis of breast cancer.

PMID- 9290500
TI  - Sex differences in the association between alcohol consumption and cognitive
      performance. EVA Study Group. Epidemiology of Vascular Aging.
AB  - Heavy alcohol drinking is associated with cognitive impairment, but little is
      known concerning the cognitive effect of moderate alcohol consumption. The
      Epidemiology of Vascular Aging (EVA) Study is a longitudinal study of cognitive
      and vascular aging. Between June 1991 and June 1993, 1,389 subjects aged 59-71
      years (574 men and 815 women) who had been recruited from the electoral rolls of
      Nantes, France, were examined. Trained psychologists administered a battery of 10
      neuropsychological tests assessing most areas of cognitive functioning. Detailed
      information on alcohol intake was collected during a structured interview. A
      multiple linear regression model was used to examine the relations between test
      scores and alcohol consumption at baseline in men and women separately,
      controlling for age, education, income, depressive symptoms, and smoking status.
      Odds ratios for being a high cognitive performer (i.e., being in the top 10% of
      the distribution of summary scores from the neuropsychological battery) were
      calculated. Among men, neuropsychological test scores were not associated with
      alcohol consumption in either univariate or multivariate analysis; nor did the
      proportion of high cognitive performers vary by alcohol consumption. In contrast,
      among women, significant positive associations between alcohol consumption and
      cognitive performance were observed for most tests in multivariate analysis. For
      example, for the Mini-Mental State Examination, the adjusted mean score for
      female nondrinkers was 27.5 and that for the heaviest drinkers 28.2 (p < 0.001).
      The odds ratio for being a high cognitive performer was 2.5 (95% confidence
      interval 1.1-5.7) for women who usually consumed two or more drinks per day in
      comparison with nondrinkers. These findings suggest that, among women, moderate
      alcohol consumption may have a beneficial effect on cognitive function.

PMID- 9290501
TI  - Declining effect of latitude on melanoma mortality rates in the United States. A
      preliminary study.
AB  - The gradient of mortality from melanoma of the skin with latitude among US whites
      was estimated from the slopes of semilogarithmic models fitted to the state
      specific mortality rates and the latitudes of the states' capital cities. The
      upward gradient of mortality from north to south for malignant melanoma of the
      skin has been decreasing since 1950-1959, when data first became available,
      through 1960-1969, 1970-1979, and 1988-1992. By the early years of the 21st
      century, rates of melanoma mortality in the contiguous United States are expected
      to be unaffected by latitude. For the country as a whole, melanoma mortality
      rates have been rising for many years. This rise has become progressively slower,
      such that national rates have been projected to stabilize in the near future.
      While increasing geographic mobility has probably played a role in reducing the
      latitude effect, melanoma mortality rates may have reached levels at which
      increased exposure of US whites to sunlight has little incremental effect.

PMID- 9290502
TI  - Proxy reporting in five areas of functional status. Comparison with self-reports
      and observations of performance.
AB  - Proxy ratings of functional status were compared with subject self-reports in
      five domains relevant to the study of older persons and with observations of
      subject performance in two areas (physical and instrumental functioning). Data
      were derived from 233 proxy-subject pairs evaluated in a prospective study of hip
      fracture patients aged 65 years or more in Baltimore, Maryland (1990-1991).
      Agreement between proxy and subject reports was highest for a summary measure of
      instrumental functioning and lowest for a measure of depression. Proxies tended
      to report more disability than did subjects, although bias varied by function.
      Patterns of agreement for proxy reports versus observations of performance
      compared with patterns for proxy reports versus subject reports were lower for
      measures of instrumental functioning, and bias was generally more extreme for
      instrumental and physical functioning measures. The authors conclude that
      agreement and bias differ by functional domain, by the way summary measures are
      created and scored, and by the criterion against which proxy reports are
      compared.

PMID- 9290503
TI  - Interviewer effects in a cohort study. Results from the Massachusetts Women's
      Health Study.
AB  - Although interviewer error is widely recognized as an important source of
      variation in epidemiologic investigations, scant published information exists
      documenting the impact of interviewer variation on study findings. Using data
      from the Massachusetts Women's Health Study, a population-based cohort study of
      2,569 middle-aged women (1982-1987), the authors evaluated interviewer variation
      in responses to different types of questions, and assessed the impact of
      interviewer variation on inferences derived from study data. Respondent
      sociodemographic and lifestyle characteristics were similar for the four study
      interviewers at the first follow-up. No interviewer variation was detected for
      questions concerning recall of specific events, but responses to questions
      regarding recall of subjective or personal information or those which required
      further probing did differ significantly by interviewer. Adjustment for
      interviewer effects had no impact on the conclusions obtained from one analysis
      of predictors of depression, despite significant interviewer variation in the
      outcome and predictor variables, but it did change conclusions from an analysis
      of the impact of support networks on psychological symptoms, wherein the
      interviewer variable was strongly related to the outcome after data were
      controlled for predictor variables. Given these findings, examination of data for
      interviewer effects is advisable despite incorporation of quality control
      measures in a study's design.

PMID- 9290504
TI  - Assessment of weighting methodology for the National Comorbidity Survey.
AB  - The authors studied weighting adjustments for the National Comorbidity Survey
      (1990-1992), a large-scale national epidemiologic investigation of the
      prevalence, risk factors, and consequences of psychiatric morbidity and
      comorbidity in the United States. Weighting adjustments for differential
      selection within households, new construction, unit nonresponse, and
      poststratification were examined separately and in combination. Specific issues
      addressed included the magnitude of the bias incurred from ignoring the weights,
      the added variance from weighting and how well this was predicted by simple
      formulae, and the performance of methods for trimming the weights. Weights had
      quite modest effects on point estimates of prevalences but resulted in major
      increases in variance unless trimmed. The weights after trimming and
      poststratification appeared to work well. It is suggested that the added variance
      from weighting be carefully monitored in similar surveys. Alternatives to the use
      of trimming for controlling variance are worth exploring.

PMID- 9290505
TI  - Two-stage sampling for etiologic studies. Sample size and power.
AB  - Preexisting computerized databases are potentially valuable sources of
      epidemiologic data. Since such databases are infrequently created specifically
      for etiologic research, data may be available for the exposure of interest and,
      through record linkage, for the endpoint of interest, but lacking for potential
      confounders. Because of the size of these databases, two-stage sampling is an
      efficient alternative to surveying the entire study population for confounder
      data. At stage 1, information on exposure and disease status is obtained for the
      entire study population. Confounder data are collected for probability-selected
      subsamples at stage 2. Logistic regression is performed on the stage 2 samples,
      with the parameter estimates and variances appropriately corrected to account for
      the stage 1 data. In this paper, the authors present methods for determining the
      required stage 2 sample size in the case of categorical exposure and confounding
      variables. Sample size tables, power curves, and a computer program have been
      produced to accommodate a binary exposure and a single binary confounder. With
      the increasing availability of preexisting yet incomplete databases, the
      potential for use of two-stage sampling will greatly increase in the future. This
      investigation provides a basis for estimating the number of participants to
      sample for the collection of confounder data at the second stage.

PMID- 9290506
TI  - Design and baseline participant characteristics of the Human Immunodeficiency
      Virus Epidemiology Research (HER) Study: a prospective cohort study of human
      immunodeficiency virus infection in US women.
AB  - The prospective, multisite human immunodeficiency (HIV) Epidemiology Research
      Study was established to define the biologic, psychologic, and social effects of
      HIV infection on the health of US women. From 1993 to 1995, a total of 871 HIV
      infected women and 439 demographically matched, uninfected women aged 16-55
      years, half of whom reported injection drug use and half of whom reported only
      sexual risk behaviors, were recruited in four US cities. Two sites recruited
      primarily from medical/drug therapy care settings, and two recruited from
      community sources. Women consented to biannual interviews; physical examination;
      blood, urine, and cervicovaginal specimen collection and repository; laboratory
      assays; and abstraction of outpatient and inpatient medical records to document
      HIV and acquired immunodeficiency syndrome-related diagnoses. Retention was
      greater than 88% at the third 6-month follow-up. Lower retention was associated
      with currently injecting drugs, not having dependent children, and not being
      infected with HIV at enrollment. In addition to the core study, a variety of
      nested studies are under way, some in collaboration with other HIV cohorts and
      various Public Health Service agencies. This cohort is distinct from other HIV
      longitudinal cohorts in the diversity of its participants and the comprehensive
      range of measures to study prospectively the biomedical, social, and emotional
      effects of the HIV epidemic on infected women and those whose behavior puts them
      at high risk of infection.

PMID- 9290507
TI  - Cancer incidence among an HIV-infected cohort. Pulmonary Complications of HIV
      Infection Study Group.
AB  - Malignancies, particularly Kaposi's sarcoma and non-Hodgkin's lymphoma (NHL), are
      associated with human immunodeficiency virus (HIV) infection. Cancer incidence
      among 1,073 asymptomatic HIV-infected individuals from the Pulmonary
      Complications of HIV Infection Study cohort, persons from six states followed
      from 1988 to 1994, was examined. Total cancer incidence was 3.99/100 person
      years; for Kaposi's sarcoma, incidence was 2.64 cases/100 person-years, and for
      NHL, it was 1.18 cases/100 person-years. Total cancer (n = 156 cases) was higher
      among nonblacks than among blacks (rate ratio = 2.8, 95% confidence interval 1.3
      6.1), with similar results for Kaposi's sarcoma and NHL. The rate of lung cancer
      (n = 5) among white, homosexual/bisexual males was 0.18 per 100 person-years,
      suggesting a high risk of lung cancer.

PMID- 9290508
TI  - Insulin and endometrial cancer.
AB  - Elevated insulin levels may explain part of the increased risk of endometrial
      cancer observed in obese postmenopausal women. Circulating sex hormones and
      fasting C-peptide levels were measured in sera obtained from 165 postmenopausal
      endometrial cancer cases accrued between June 1, 1987, and May 15, 1990, from
      hospitals in Chicago, Illinois; Hershey, Pennsylvania; Irvine and Long Beach,
      California; Minneapolis, Minnesota; and Winston-Salem, North Carolina, and 180
      community and hysterectomy controls. Women with a personal history of diabetes
      were excluded. Among controls, C-peptide was positively correlated with body mass
      index (BMI) ((r = 0.44), waist-to-thigh circumference ratio ((r = 0.24), estrone
      ((r = 0.18), and estradiol ((r = 0.28) (albumin-bound (r = 0.45), and free (r =
      0.37)) and negatively correlated with sex hormone-binding globulin (r = -0.48).
      In age-adjusted analyses, the odds ratios and 95% confidence intervals for
      tertiles of C-peptide and endometrial cancer were, from lowest to highest: 1.0
      (reference), 0.78 (95% confidence interval (CI) 0.43-1.4), and 2.2 (95% CI 1.3
      3.7). Further adjustment for BMI substantially attenuated the odds ratios for the
      highest tertile of C-peptide (odds ratio = 1.2, 95% CI 0.63-2.1), and adjustment
      for body mass index and other risk factors for endometrial cancer eliminated the
      association (odds ratio = 1.0, 95% CI 0.55-2.0). In contrast, adjustment for C
      peptide had little influence on the magnitude of the positive associations
      between body mass index (odds ratio for highest vs. lowest tertile, without and
      with adjustment for C-peptide = 4.1 (95% CI 2.3-7.5) and 3.7 (95% CI 1.9-7.1),
      respectively) or several steroid hormones and endometrial cancer. These data are
      not consistent with the hypothesis that the effect of obesity on endometrial
      cancer risk is mediated through high insulin levels.

PMID- 9290509
TI  - Association of coronary heart disease incidence with carotid arterial wall
      thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC)
      Study, 1987-1993.
AB  - Few studies have determined whether greater carotid artery intima-media thickness
      (IMT) in asymptomatic individuals is associated prospectively with increased risk
      of coronary heart disease (CHD). In the Atherosclerosis Risk in Communities
      Study, carotid IMT, an index of generalized atherosclerosis, was defined as the
      mean of IMT measurements at six sites of the carotid arteries using B-mode
      ultrasound. The authors assessed its relation to CHD incidence over 4-7 years of
      follow-up (1987-1993) in four US communities (Forsyth County, North Carolina;
      Jackson, Mississippi; Minneapolis, Minnesota; and Washington County, Maryland)
      from samples of 7,289 women and 5,552 men aged 45-64 years who were free of
      clinical CHD at baseline. There were 96 incident events for women and 194 for
      men. In sex-specific Cox proportional hazards models adjusted only for age, race,
      and center, the hazard rate ratio comparing extreme mean IMT (> or = 1 mm) to not
      extreme (< 1 mm) was 5.07 for women (95% confidence interval 3.08-8.36) and 1.85
      for men (95% confidence interval 1.28-2.69). The relation was graded (monotonic),
      and models with cubic splines indicated significant nonlinearity. The strength of
      the association was reduced by including major CHD risk factors, but remained
      elevated at higher IMT. Up to 1 mm mean IMT, women had lower adjusted annual
      event rates than did men, but above 1 mm their event rate was closer to that of
      men. Thus, mean carotid IMT is a noninvasive predictor of future CHD incidence.

PMID- 9290510
TI  - Alcohol consumption and coronary heart disease morbidity and mortality.
AB  - Alcohol consumption is associated with a reduced risk of coronary heart disease
      (CHD) but an increased risk of other causes of morbidity and mortality. It
      remains unclear whether there is an upper limit to a protective effect of alcohol
      intake on CHD risk. Whether there is a U- or an L-shaped relation between alcohol
      consumption and CHD incidence (hospitalization and mortality due to ischemic
      heart disease: International Classification of Diseases codes 410-414) is
      examined using the National Health and Nutrition Examination Survey I. Baseline
      data were collected in 1971-1975. Follow-up data through 1987 (14.6 years mean
      follow-up) were analyzed for 6,788 European-American males (n = 2,960) and
      females (n = 3,828) aged 40-75 years at baseline. Cox regression was used to
      assess the association between alcohol consumption and incidence of CHD. For
      females, an increased risk was found above 28 drinks per week relative to
      abstainers (relative risk = 2.6, 95% confidence interval 1.2-5.5), which was
      significant, but was based on small numbers. For males, no upturn in risk was
      found at higher intake. Mortality data supported these results. Sex differences
      should be explored further, since they are relevant to understanding causal
      mechanisms and public policy and prevention.

PMID- 9290511
TI  - Hip fracture incidence among elderly Asian-American populations.
AB  - This study estimated national age- and sex-specific nontraumatic hip fracture
      incidence rates for elderly Chinese Americans, Japanese Americans, and Korean
      Americans. Based on a 50 percent sample of 1992 Medicare enrollees with the
      race/ethnicity code "Asian" and "other," cohorts of persons with distinctive
      Chinese (n = 24,366), Japanese (n = 28,762), and Korean (n = 5,470) names were
      followed passively for 2 years for a hospitalization with a diagnostic code
      indicating hip fracture. Cohorts of whites and blacks were followed for
      comparison. Year of immigration was deduced from the year of issuance of the
      Social Security number. Age-adjusted hip fracture incidence was lower for all
      three Asian-American groups than for whites. For females, the standardized
      fracture ratio relative to whites was 30.1 for Chinese, 73.2 for Japanese, and
      52.8 for Koreans; for males, the standardized fracture ratio was 41.9 for
      Chinese, 58.1 for Japanese, and 90.7 for Koreans. Persons whose Social Security
      numbers were issued after the immigration Act of 1965 had an adjusted relative
      risk of 1.37 (95% confidence interval 1.05-1.78) compared with those in the US
      before that year, after adjustment for age, sex, and ethnic group.

PMID- 9290512
TI  - Effects of social support and personal coping resources on mortality in older
      age: the Longitudinal Aging Study Amsterdam.
AB  - This study focuses on the role of social support and personal coping resources in
      relation to mortality among older persons in the Netherlands. Data are from a
      sample of 2,829 noninstitutionalized people aged between 55 and 85 years who took
      part in the Longitudinal Aging Study Amsterdam in 1992-1995. Social support was
      operationally defined by structural, functional, and perceived aspects, and
      personal coping resources included measures of mastery, self-efficacy, and self
      esteem. Mortality data were obtained during a follow-up of 29 months, on average.
      Cox proportional hazards regression models revealed that having fewer feelings of
      loneliness and greater feelings of mastery are directly associated with a reduced
      mortality risk when age, sex, chronic diseases, use of alcohol, smoking, self
      rated health, and functional limitations are controlled for. In addition, persons
      who received a moderate level of emotional support (odds ratio (OR) = 0.49, 95%
      confidence interval (CI) 0.33-0.72) and those who received a high level of
      support (OR = 0.68, 95% CI 0.47-0.98) had reduced mortality risks when compared
      with persons who received a low level of emotional support. Receipt of a high
      level of instrumental support was related to a higher risk of death (OR = 1.74,
      95% CI 1.12-2.69). Interaction between disease status and social support or
      personal coping resources on mortality could not be demonstrated.

PMID- 9290513
TI  - On measures of agreement calculated from contingency tables with categories
      defined by the empirical quantiles of the marginal distributions.
AB  - Epidemiologists sometimes collect bivariate continuous data on a number of
      subjects, compute the empirical (sample) quantiles of the marginal data, and then
      use these values to partition the original data into two-way contingency tables.
      Tables created in this manner have row and column categories defined by the
      random empirical marginal quantiles rather than by preset cutpoints, so these
      tables have fixed marginal totals. Hence, instead of the conventional multinomial
      distribution, these tables have the empirical bivariate quantile-partitioned
      (EBQP) distribution. In this paper, the authors demonstrate how to use empirical
      methods appropriate for EBQP tables to make inferences and construct confidence
      intervals for three commonly used measures of agreement: kappa, weighted kappa,
      and another class of measures derived from conditional proportions in the extreme
      rows of the table. They also show that if one incorrectly applies conventional
      methods appropriate for multinomial tables to statistics calculated from EBQP
      tables, one can obtain substantially misleading results. In addition, the authors
      present alternative parametric methods for estimating these measures of agreement
      and illustrate corresponding methods of inference and confidence interval
      construction. Finally, they show that these empirical (EBQP) methods can have low
      efficiency compared with parametric methods for some of these measures of
      agreement.

PMID- 9290514
TI  - Re: "Invited commentary: response to Science article, 'Epidemiology faces its
      limits'".

PMID- 9290515
TI  - Re: "Time-to-event analysis of longitudinal follow-up of a survey: choice of the
      time-scale".

PMID- 9290516
TI  - Subclavian artery injuries.
AB  - Thirty-two consecutive patients with subclavian artery injuries were evaluated to
      assess the mechanism of injury, types of repair, and results. In this series,
      most wounds were from firearms. Although the mortality was high (19%), most
      patients had the vessel repaired successfully. Associated injuries, especially to
      neural structures, led to significant morbidity. Principles used in dealing with
      these injuries should be 1) proximal and distal control prior to exposing the
      injury site, 2) reestablishing distal circulation through primary repair or graft
      placement, and 3) identifying and treating associated injuries.

PMID- 9290517
TI  - Intraoperative photoplethysmographic diagnosis of ischemic colitis.
AB  - Intraoperative evaluation of ischemic colitis presents several problems related
      to diagnosis, severity, and extension. The aim of this study was to determine the
      usefulness of photopletysmography (PPG) to detect colonic arterial wave amplitude
      changes in patients operated on for ischemic colitis, comparing the affected area
      with a control area on the transverse colon. Four patients were studied, two with
      gangrenous colitis, and two with protracted "transient" ischemic colitis. All
      four patients survived. PPG is a useful method for intraoperative diagnosis and
      surgical assessment of ischemic colitis.

PMID- 9290518
TI  - Effectiveness of cholecystokinin-stimulated cholescintigraphy in the diagnosis
      and treatment of acalculous gallbladder disease.
AB  - We retrospectively reviewed the medical records of 107 patients in two community
      hospitals who had undergone cholecystokinin-stimulated cholescintigraphy with
      ejection fraction to determine whether this test is reliable in identifying
      patients whose symptoms will improve following cholecystectomy. Patients with
      cholelithiasis or incomplete medical records and patients who could not be
      interviewed were excluded from the study. Forty-two of 58 study patients (72%)
      had an abnormal ejection fraction (defined as 35% or less); 27 of 42 patients
      (64%) underwent cholecystectomy. Twenty-six of 27 (96%) reported lessening of or
      resolution of symptoms following cholecystectomy. Sixty-seven per cent of the
      surgical specimens from the 27 patients demonstrated chronic cholecystitis.
      Fifteen of 42 patients (36%) with abnormal ejection fractions did not undergo
      cholecystectomy; 12 of 15 (80%) also reported lessening or resolution of
      symptoms. Of the 16 of 58 patients with a normal ejection fraction, 2 underwent
      cholecystectomy and reported resolution of symptoms. Five of 14 (36%) with normal
      ejection fractions who did not undergo cholecystectomy reported improvement. In
      this series, most patients with an abnormal ejection fraction had lessening of
      symptoms regardless of whether they underwent cholecystectomy.

PMID- 9290519
TI  - The prevention of experimentally induced postoperative adhesions.
AB  - For many years, various substances have been used to prevent postoperative
      adhesions, with suboptimal effectiveness. Saline has been postulated to have a
      positive effect, but it is reabsorbed from the abdominal cavity within 24 hours.
      To determine whether a longer-lasting intraperitoneal solution would be effective
      in preventing postoperative adhesions, 36 rats were divided into three groups: in
      15 rats, a 2.5 per cent hyperosmolar solution of peritoneal dialysis fluid was
      injected intraperitoneally immediately following exploratory laparotomy, which
      included traumatization of the intestinal serosa at two sites; in 12 rats, normal
      saline was injected by the same procedure; and in 9 rats, no fluid was injected
      after the same operation. After 3 weeks, the group receiving the hyperosmolar
      peritoneal dialysis solution achieved the best results in both sites, the group
      that received normal saline showed marginal improvement, and the control group
      fared the worst.

PMID- 9290520
TI  - Acute appendicitis secondary to metastatic bronchogenic adenocarcinoma.
AB  - Metastatic tumors to the appendix are not common. However, these tumors should be
      one of the differential diagnoses in patients with known primary malignancy, who
      present with signs and symptoms of acute appendicitis. We report a case of an
      elderly male with poorly differentiated bronchogenic adenocarcinoma which
      metastasized to the appendix.

PMID- 9290521
TI  - Noniatrogenic pediatric vascular trauma: a ten-year experience at a level I
      trauma center.
AB  - We retrospectively reviewed all pediatric patients (< 18 years old) who presented
      to a Level I trauma center from 1984 to 1994 with noniatrogenic vascular trauma.
      There were 48 patients (42 male and 6 female) ages 2 to 17 years. Mechanism of
      injury included gunshot wounds (34) stab wounds (10), and blunt trauma (4). The
      lower extremities were most commonly injured (31), followed by upper extremity
      (17), trunk (8), and neck (4). Twenty-one (44%) patients had associated
      nonvascular injuries (primarily orthopedic or peripheral nerve). Eighteen (37%)
      patients underwent preoperative angiography for suspected extremity (15) or
      carotid injuries (3). Twenty-nine patients went to surgery without angiography
      based on severe ischemia (11) or hemorrhage (18). Arterial injuries (45) were
      managed by interposition reverse saphenous vein graft (16), primary repair (15),
      ligation (5), or other operative (5) and nonoperative treatment (4). Venous
      injuries (15) were treated with primary repair (8), patch (3), ligation (3), and
      nonoperative management (1). Fasciotomy was performed in six (12%). There were
      three deaths (6%), all due to aortic and/or caval injuries. Limb salvage in
      survivors was 100 per cent. There were no complications from angiography.
      Postoperative duplex scans demonstrated patency in six of the seven patients
      studied with venous injuries. We conclude that 1) noniatrogenic pediatric
      vascular trauma is uncommon, and 2) using an aggressive approach to both the
      diagnosis and treatment of these injuries can achieve excellent limb salvage
      rates with a low morbidity and mortality.

PMID- 9290522
TI  - Resection of a bronchogenic cyst involving the wall of the mainstem bronchus and
      repair utilizing a pedicled pericardial flap.
AB  - Symptomatic bronchogenic cysts should be completely resected because of
      uncertainties in diagnosis, to prevent recurrence, and to avoid late
      complications. Infrequently, these cysts may involve the proximal
      tracheobronchial tree. Often such cysts are incompletely excised with less than
      optimal results. A case of a patient with a bronchogenic cyst involving the wall
      of the right mainstem bronchus is presented. The cyst was completely excised and
      the bronchus repaired using a pedicled pericardial flap. The procedure may serve
      as the preferred method of reconstruction in such circumstances.

PMID- 9290524
TI  - Cryosurgery causes a profound reduction in tumor markers in hepatoma and
      noncolorectal hepatic metastases.
AB  - Cryosurgical ablation of hepatic metastases from colon carcinoma has become a
      useful adjunct in the management of patients whose tumors are not amenable to
      surgical resection. We evaluated cryoablation of hepatoma and noncolorectal
      hepatic metastases by examining its effect on serum levels of tumor markers in 20
      patients with primary liver cancer (N = 5) or liver metastases (N = 15) from
      breast cancer, neuroendocrine tumors, ovarian cancer, and thyroid cancer. All
      patients had failed conventional therapy and had no evidence of extrahepatic
      spread. After cryosurgery, 17 patients had a significant decrease in tumor marker
      levels (median 77%) and a significant improvement in symptoms. One patient died
      of nontumor causes, and five patients died of recurrent disease. Median interval
      to death or last follow-up was 28.3 months overall (range, 2-45 months), 17.9
      months for nonsurvivors (range, 2-44 months), and 35.2 months for survivors
      (range, 26-45 months). Median survival was 32 months following curative surgery
      (range, 16-45 months) and 25 months following palliative surgery (range, 2-42
      months). Cryosurgical ablation of noncolorectal hepatic metastases and primary
      hepatomas produces a profound reduction in serum levels of tumor markers. It is
      safe, provides excellent palliation of symptoms, and in selected patients can be
      performed with curative intent.

PMID- 9290523
TI  - Pneumostasis of experimental air leaks with a new photopolymerized synthetic
      tissue sealant.
AB  - Air leak is a major contributor to increased length of stay and postoperative
      morbidity following pulmonary surgery. The effectiveness of a new
      photopolymerized synthetic hydrogel (FocalSeal, Focal, Inc., Lexington, MA) as a
      sealant for pulmonary air leaks was determined in 10 mongrel dogs (20-35 kg). The
      animals were anesthetized and underwent left-sided anterolateral thoracotomy with
      amputation of a 2 x 3-cm segment of the lung apex. Hemostasis was achieved and
      terminal bronchial openings of 1.5 to 3 mm with vigorous air leaks were
      identified. After successful injury, the dogs were randomly assigned to sealant
      (n = 5) or control (n = 5) groups. In treated animals, the sealant was applied by
      brushing the solution to the cut parenchymal surface and solidified while briefly
      interrupting ventilation (40-60 seconds) using visible illumination (450-550 nm)
      from a xenon light source. Controls received no sealant. A single chest tube was
      maintained at the injury site with a continuous negative pressure of 20 cm of
      water. All dogs were extubated and allowed to breathe spontaneously under
      sedation for 24 hours. Chest radiographs were taken postsurgery and presacrifice.
      All control animals (n = 5) showed persistent vigorous air leak for the duration
      of the 24-hour observation period. All treated air leaks resolved immediately,
      and four of five remained sealed throughout the observation period. One leak
      reappeared after 17 hours due to inadequate sealant thickness over a 3-mm
      terminal bronchus. Gross evaluation of the treatment group at the end of 24 hours
      demonstrated intact sealant well adherent to the parenchyma. No evidence of
      atelectasis or excessive edema was seen, and no sealant-related complications or
      toxic effects were noted. Radiologically, lungs were fully inflated. Histologic
      evaluation at 24 hours revealed no evidence of a strong cellular response to the
      synthetic sealant, and no fibrosis or adhesions were seen, the onset of the
      healing process was favorable, indicating good biocompatability. In conclusion,
      this material was found to be an effective means for sealing bronchial and
      parenchymal air leaks in this model and warrants clinical evaluation.

PMID- 9290525
TI  - Prevention of compartment syndrome associated with dorsal lithotomy position.
AB  - There is a clear association between the dorsal lithotomy position and the
      development of a postoperative compartment syndrome. Compartment syndrome occurs
      when elevated pressure in an osteofascial compartment compromises local perfusion
      and often results in neurovascular damage and permanent disability. Surgeons must
      recognize this association and provide appropriate preventative measures, have a
      high index of suspicion in all patients, and be prepared to make an early
      diagnosis when it is encountered. We will report four cases we encountered,
      discuss the etiology, analyze the literature, and propose a modification on
      patient positioning that has minimized the incidence of compartment syndrome at
      our institution. A variety of intraoperative events, including hypotension,
      hypoxemia, leg elevation, hip and knee flexion, direct pressure, and compressive
      bandages may all contribute to compartmental ischemia. Ischemia is followed by
      reperfusion, capillary leakage from the ischemic tissue, and a further increase
      in tissue edema. Increased edema causes further embarrassment of perfusion and
      perpetuation of the cycle, ultimately resulting in neuromuscular compromise
      secondary to ischemia. To prevent this destructive cycle, emphasis must be placed
      on maintaining a high index of suspicion in all patients, minimizing leg
      elevation, and on the importance of early diagnosis and intervention.

PMID- 9290526
TI  - Lymphoma of the extrahepatic biliary ducts in acquired immunodeficiency syndrome.
AB  - Gastrointestinal neoplasia in acquired immunodeficiency syndrome (AIDS)
      frequently presents as a non-Hodgkin's lymphoma or Kaposi's sarcoma, at sites
      including the oral cavity, esophagus, small bowel, and mesenteries. Primary
      lymphoma of the biliary ducts, even in the setting of AIDS, is rare. This
      patient, an older male with no preoperatively known AIDS risk factors, presented
      with painless jaundice and radiographic findings of focal hepatic duct stenosis,
      suggesting either a Klatskin tumor or sclerosing cholangitis. Only after the
      pathologic diagnosis of a malignant large cell lymphoma from the en bloc tumor
      specimen was his human immunodeficiency virus status ascertained and noted to be
      positive.

PMID- 9290527
TI  - Factors predicting prolonged mechanical ventilation in critically injured
      patients: introducing a simplified quantitative risk score.
AB  - Our objective was to identify a set of readily available and easily obtainable
      parameters that would predict prolonged mechanical ventilation in the critically
      injured patient. A surgical intensive care unit of an academic Level I trauma
      center. Prospectively collected data were retrospectively analyzed on all
      critically injured patients receiving mechanical ventilation for more than 2 days
      between January and December 1994. Prolonged mechanical ventilation (PMV) was
      defined as the need for mechanical ventilatory support for more than 7 days. One
      hundred and nineteen patients entered the final analysis. Of these, 63 remained
      on the ventilator for 7 days or less and 56 for more than 7 days. The Injury
      Severity Score (ISS), partial arterial oxygen tension (PaO2)/inspired fraction of
      oxygen (FiO2), net fluid balance, and use of Swan-Ganz were significantly
      different between the two groups when calculated 48 hours after surgical
      intensive care unit admission. Furthermore, we dichotomized these four variables
      across cutpoints that were determined by statistical analysis (ISS more or less
      than 20, PaO2/FiO2 more or less than 250, fluid retention more or less than 2000
      cc, and presence or absence of Swan-Ganz). Again, significantly more patients
      required PMV if they had any one of the following: Swan-Ganz, ISS more than 20,
      PaO2/FiO2 less than 250, or fluid retention more than 2000 cc at 48 hours. An
      easily calculated five-point risk score (0-4 points) for predicting PMV based on
      these four variables was developed. Among the 35 patients at the extremes of the
      risk score (0 or 4 points), 33 (94.3%) were correctly prognosticated as to their
      needs for PMV. The need for an easily calculated score, which is derived from
      readily available parameters and can reliably identify patients with prolonged
      needs for ventilatory support, is obvious in the trauma setting. We describe a
      five-point risk score by which we can predict the need for PMV early in the
      course of the disease. Resource utilization and personnel allocation issues, as
      well as important therapeutic procedures, can be planned based on this score.

PMID- 9290528
TI  - Prevention of adhesions by Seprafilm, an absorbable adhesion barrier: an
      incisional hernia model in rats.
AB  - Adhesion formation, which is almost inevitable following incisional hernia repair
      with prosthetic mesh, may lead to intestinal obstruction and enterocutaneous
      fistulae. Physical barriers, namely carboxymethylcellulose and hyaluronic acid,
      have been reported to lessen the intra-abdominal adhesions. To evaluate the
      effects of Seprafilm (Genzyme Corp., Cambridge, MA), a bioresorbable, translucent
      membrane composed of carboxymethylcellulose and hyaluronic acid, in the presence
      of a foreign body such as polypropylene mesh, an incisional hernia model in rats
      was used. Twenty-four male rats were divided into two groups: control (12) and
      Seprafilm (12). A defect, measuring 1.5 x 2.5 cm, was created in each animal.
      Control animals had the polypropylene mesh sutured to the defect, whereas in the
      other group, two membranes of Seprafilm were laid over the abdominal viscera
      before repair with polypropylene mesh. Half of the animals from each group were
      killed at postoperative day 7 and remaining half at day 30 for adhesion scoring
      and histological evaluation of wound healing. Seprafilm animals had fewer
      adhesions compared with control animals (P = 0.0008). Seprafilm had no adverse
      effect on wound healing. This membrane seems to have the potential to lessen the
      adhesion-related morbidity following incisional hernia repair.

PMID- 9290530
TI  - The gluteal compartment syndrome.
AB  - The gluteal compartment syndrome is a rare, often unrecognized condition which,
      left untreated, can lead to renal failure, sepsis, and death. The etiology,
      physiology, and manifestations are similar to those seen in the more common and
      readily recognized compartment syndromes of the lower leg and forearm. The large
      gluteal muscle mass confined by the fascia lata of the thigh and tensor fascia
      lata can, under the right conditions, produce muscle necrosis, acidosis,
      elevations of creatinine phosphokinase, and ultimately renal failure. A gluteal
      compartment syndrome most commonly occurs in individuals with an altered mental
      status due to drugs or alcohol who remain in one position for an extended period
      of time. This prolonged compression leads to muscle damage, edema, and a full
      blown compartment syndrome. Due to its anatomic location and rarity, diagnosis is
      missed or delayed, resulting in significant morbidity and possible mortality. The
      mainstay of treatment consists of fasciotomy and debridement.

PMID- 9290529
TI  - Laparoscopic adrenalectomy in asymptomatic pheochromocytoma.
AB  - A patient with asymptomatic pheochromocytoma associated with catecholamine
      hypersecretion but no hypertension was treated by right laparoscopic
      adrenalectomy. The 63-year-old male patient was referred to us for treatment of
      an incidentaloma. The diameter of the adrenal tumor was 50 mm, and the peripheral
      blood nonrepinephrine level was 1.12 ng/ml (normal level, 0.4 ng/ml). Blood
      pressure was normal. A flexible electron laparoscope was used for open
      laparoscopy, and four trocars were inserted. The retroperitoneum was incised to
      the right of the inferior vena cava, and the tumor was excised. During the
      operation, blood pressure rose transiently, and a blocker and nitroglycerin were
      administered. The tumor bled extremely easily. The duration of surgery was 3
      hours and 20 minutes, and blood loss was 210 ml. The excised tumor was 55 mm in
      diameter. The patients's postoperative course was uneventful. If the size of
      asymptomatic pheochromocytoma is not large, and blood pressure and cardiac
      function are stable, laparoscopic adrenalectomy is indicated for this type of
      tumor as long as it is performed by experienced surgeons.

PMID- 9290531
TI  - The impact of image-directed core biopsy on the practice of breast surgery: a new
      algorithm for a changing technology.
AB  - Open surgical biopsy has long been the standard of care for the diagnosis of
      breast pathology. As more lesions are diagnosed by mammography, image-directed
      core biopsy has taken on increasing importance. This study consisted of a
      consecutive group of 540 patients who underwent breast biopsy for
      mammographically or sonographically detected lesions. The percentage of those
      undergoing image-directed biopsy and open biopsy were determined as well as the
      rate of positive biopsy for each method. Results showed that for patients with
      nonpalpable lesions, the proportion of image-directed core biopsies rose steadily
      during the study period, from 0 per cent in early 1993 to 70.1 per cent by early
      1996. During this same period, positive biopsy rate rose from 23.9 to 31.0 per
      cent in the first 18 months of the study to a range of 45.2 to 48.3 per cent in
      the last 18 months. It was concluded that image-directed core biopsies have begun
      to impact the practice of breast surgery by replacing, to a great extent, the
      open surgical biopsy. This study also demonstrates an increased proportion of
      positive biopsies done by open surgical technique. It was suggested that many of
      the mammographically benign lesions are diagnosed by image-directed core biopsy,
      obviating the need for an open technique. An algorithm for managing nonpalpable
      breast lesions is presented.

PMID- 9290532
TI  - Absorbable, delayed-release antibiotic beads reduce surgical wound infection.
AB  - Absorbable, polyglycolic acid (PGA) beads were evaluated as a new vehicle for
      local antibiotic delivery. Incisions on the dorsa of guinea pigs were
      contaminated with 1 x 10(8) Escherichia coli and 1 x 10(8) Staphylococcus aureus.
      PGA beads containing either minocycline, amikacin, or no antibiotic (placebo)
      were placed into these wounds and compared to animals treated with systemic
      minocycline or amikacin alone. The diameter of wound erythema was measured daily
      for 7 days. Serial blood and wound quantitative cultures were obtained, and serum
      and wound antibiotic concentrations were determined. Both minocycline-PGA and
      amikacin-PGA-treated wounds exhibited less erythema than placebo-PGA wounds (P <
      0.05). All minocycline-PGA and amikacin-PGA-treated wounds healed primarily,
      whereas 67 per cent of placebo-PGA wounds developed purulence, dehisced, and
      healed secondarily. Local antibiotic delivery was more effective than systemic
      administration in reducing wound erythema and the number of bacteria in wound
      quantitative cultures. E. coli and S. aureus were quantitatively reduced (P <
      0.05) in wounds of antibiotic PGA-treated animals compared to those in placebo
      PGA-treated and systemic minocycline and systemic amikacin-treated animals.
      Measurable minocycline and amikacin concentrations were present in antibiotic-PGA
      treated wounds through day 3, without detectable serum levels. Delayed-release,
      absorbable, antibiotic-containing PGA beads effectively prevent infection in
      contaminated wounds and have the advantage of not requiring vehicle removal.

PMID- 9290533
TI  - Limb revascularization to stimulate bone fracture healing.
AB  - A case of nonunion of a tibial fracture and traumatic occlusion of the
      superficial femoral artery is presented. Bone healing and consolidation occurred
      dramatically after revascularization was performed.

PMID- 9290535
TI  - Re: Laparoscopic cholecystectomy in the third trimester of pregnancy.

PMID- 9290536
TI  - Re: The Delorme procedure: a useful operation for complicated rectal prolapse in
      the elderly.

PMID- 9290534
TI  - A two-layer "telescoping" proximal anastomosis for repair of juxtarenal abdominal
      aortic aneurysms.
AB  - A two-layer proximal aortic anastomosis for juxtarenal abdominal aortic aneurysm
      resulting in satisfactory "match" between Dacron graft and aorta is obtained.
      With this technique we are able to avoid additional suture and carotid bleeding
      from the suture line. Follow-up aortograms and computerized tomography of the
      aorta have shown complete exclusion of aneurysmal portion of juxtarenal aorta.

PMID- 9290537
TI  - Is there a glycemic threshold?

PMID- 9290538
TI  - Case of the month. Autopsy Committee of the College of American Pathologists.

PMID- 9290540
TI  - Superficial thrombophlebitis and deep vein thrombosis. A controversial
      association.
AB  - BACKGROUND: Superficial thrombophlebitis is a common and benign disease. However,
      an association with deep vein thrombosis, a more severe condition that requires
      anticoagulant treatment, has been reported repeatedly with frequencies ranging
      from 12% to 44%. METHODS: All consecutive records of patients with lower limb
      superficial thrombophlebitis were retrieved from the laboratory database over a 6
      year period (1989-1994), and association with deep vein thrombosis was sought.
      Also, to detect late events, consultations were registered over a 3-month period
      after the initial examination. Patients with the association of superficial
      thrombophlebitis and deep vein thrombosis were also compared with a randomly
      selected sample of subjects with superficial thrombophlebitis only. RESULTS:
      Objectively confirmed deep vein thrombosis was detected in 31 patients (5.6%; 95%
      confidence interval, 3.8%-7.9%). Additional late thromboembolic events were
      detected in 1.7% of the patients during the 3-month follow-up period. Previous
      immobilization was more common among patients with deep vein thrombosis
      associated with superficial phlebitis (11/31, 36%) than among a randomly selected
      subset of patients with superficial thrombophlebitis only (13/93, 14%), the
      difference being statistically significant (P < .02). CONCLUSIONS: When large
      populations of patients with superficial thrombophlebitis are studied, the
      association with deep vein thrombosis appears rather small. Thus, systematic
      screening for deep vein thrombosis may not be warranted in the presence of
      superficial thrombophlebitis unless additional risk factors (eg, immobilization)
      are present.

PMID- 9290539
TI  - Pathophysiology of type 2 diabetes and modes of action of therapeutic
      interventions.
AB  - At least 90% of the 12 to 15 million persons with diabetes mellitus in the United
      States, half of whose condition remains undiagnosed, have type 2 diabetes. Type 2
      diabetes is preceded by a long period of impaired glucose tolerance, a reversible
      metabolic state associated with increased prevalence of macrovascular
      complications. Thus, at the time of diagnosis, long-term complications have
      developed in almost one fourth of patients. Susceptibility to type 2 diabetes
      requires genetic (most likely polygenic) and acquired factors, and its
      pathogenesis involves an interplay of progressive insulin resistance and beta
      cell failure. The ideal treatment of type 2 diabetes should reverse insulin
      resistance and beta-cell dysfunction in most treated patients and prevent, delay,
      or reverse long-term complications. Current strategies are aimed at amelioration
      of insulin resistance (diet, exercise, weight loss, and metformin and
      troglitazone therapy), augmentation of insulin supply (sulfonylurea and insulin
      therapy), or limitation of postprandial hyperglycemia (acarbose therapy). Future
      therapies probably will target (1) insulin resistance, using a multifaceted
      approach; (2) hepatic glucose production, using gluconeogenesis inhibitors; (3)
      excess nonesterified fatty acid production, using lipolysis inhibitors; and (4)
      fat oxidation, using carnitine palmitoyltransferase I and II inhibitors. Attempts
      also could be made to stimulate energy expenditure and increase nonoxidative
      glucose disposal by means of beta 3-adrenoceptor agonists. One promising strategy
      is an attack on multiple pathophysiological processes by combining antidiabetic
      agents with disparate mechanisms of action. Thus, we now have unprecedented
      resources for drug therapy for diabetes, with great opportunity for innovative
      combinations. It is hoped that these expanded choices will provide the tools
      necessary for a more efficient management of type 2 diabetes and prevention of
      its long-term complications.

PMID- 9290541
TI  - Human immunodeficiency virus disease-related neutropenia and the risk of
      hospitalization for bacterial infection.
AB  - BACKGROUND: Neutropenia is common in patients with human immunodeficiency virus
      (HIV) disease. However, the degree of risk for serious bacterial infections
      associated with various levels of neutropenia in patients with HIV disease is not
      well defined. METHODS: A retrospective analysis of databases containing
      demographic information for patients attending the San Francisco General Hospital
      HIV outpatient clinic, test results reported by the hospital's clinical
      laboratory, and the San Francisco General Hospital inpatient International
      Classification of Diseases, Ninth Revision (ICD-9) hospital discharge diagnosis
      codes from October 1, 1992, through November 30, 1993. Risk window time periods
      were defined, encompassing dates that consecutive absolute neutrophil counts
      (ANCs) occurred in a single ANC stratum. One risk window at the lowest ANC
      stratum for each patient was analyzed for hospitalizations with ICD-9 codes
      indicating bacterial infections. A 5% random sample of medical records was
      reviewed for end point validation. RESULTS: Codes from ICD-9 had 98% and 96%
      positive and negative predictive values, respectively, for meeting National
      Institute of Allergy and Infectious Diseases Division of AIDS [acquired
      immunodeficiency syndrome] clinical trial end point definitions for bacterial
      infections. Among 2047 evaluable patients, a significant increase in the
      incidence of hospitalization for serious bacterial infections was observed for
      those in the ANC strata of 500 to 749 X 10(6)/L and below. The 95% confidence
      intervals for the incidence of hospitalization associated with each ANC stratum
      below 500 X 10(6)/L did not overlap with that for any stratum of 750 X 10(6)/L or
      higher (22-117 vs 0.4-19 patient hospitalizations per 10000 days at risk,
      respectively). A multivariate analysis revealed only the severity and duration of
      neutropenia and black race to be significant end point predictors. CONCLUSION:
      Among 2047 patients with HIV disease, significantly higher risks of
      hospitalization for bacterial infections were associated with ANCs lower than 750
      X 10(6)/L, especially for ANCs lower than 500 X 10(6)/L.

PMID- 9290542
TI  - Cause of acute tubular necrosis affects its prognosis. The Auriculin Anaritide
      Acute Renal Failure Study Group.
AB  - BACKGROUND: Acute tubular necrosis (ATN) is the most common type of acute renal
      failure in hospitalized patients and is associated with a high morbidity and
      mortality. The cause of ATN can be divided into nephrotoxic, ischemic, or mixed.
      OBJECTIVE: To test the hypothesis that the cause of ATN affects its clinical
      outcome. METHODS: The study compares clinical outcomes of patients enrolled in
      the placebo arm of a multicenter, randomized, double-blinded, placebo-controlled
      trial of anaritide (Auriculin, synthetic atrial natriuretic peptide, Scios,
      Mountain View, Calif) in patients with well-defined ATN. Patients were divided
      prospectively into groups according to the cause of ATN: pure nephrotoxic, pure
      ischemic, or mixed nephrotoxic and ischemic. Outcomes of interest were dialysis
      free survival and all-cause mortality on day 14 and day 21. The causal groups
      were compared with respect to the prevalence of several comorbidities suspected
      of affecting the clinical outcomes. RESULTS: Mortality was 10% in the nephrotoxic
      group and 30% in the ischemic group on day 21. Dialysis-free survival was 66% in
      the nephrotoxic group and 41% in the ischemic group on day 21. Outcomes in the
      mixed and ischemic groups were similar. Compared with the nephrotoxic group,
      there was a significantly higher prevalence of cardiogenic shock, hypotension,
      sepsis, and respiratory failure and a tendency toward a higher prevalence of
      acute hepatic dysfunction in the ischemic group. Diabetes mellitus was more
      prevalent in the nephrotoxic group. Among patients with ischemic ATN, dialysis
      free survival improved significantly and mortality tended to decline with
      advancing age. CONCLUSIONS: Among patients with ATN, those in whom renal ischemia
      was causative had significantly higher mortality and lower dialysis-free survival
      than those whose ATN was purely nephrotoxic in origin. This difference in
      clinical outcomes was associated with a higher prevalence of serious
      commorbidities in the ischemic ATN group. Advancing age was associated with
      improved dialysis-free survival and a tendency toward reduced mortality in
      patients with ischemic ATN.

PMID- 9290543
TI  - Variation in the use of do-not-resuscitate orders in patients with stroke.
AB  - OBJECTIVES: To identify sociodemographic and clinical characteristics associated
      with the use of do-not-resuscitate (DNR) orders in hospitalized patients with
      stroke. To examine whether the use of DNR orders varies across hospitals.
      METHODS: This observational cohort study used data collected for 13337
      consecutive eligible patients with a primary diagnosis of stroke. These patients
      were discharged in 1991 through 1994 from 30 hospitals in a large metropolitan
      area. Study data were abstracted from patients' hospital records using standard
      forms. Admission severity of illness was measured using a validated multivariable
      model. Sociodemographic and clinical factors independently associated with the
      use of DNR orders were identified using stepwise logistic regression. RESULTS: Do
      not-resuscitate orders were written for 2898 patients (22%). Patient
      characteristics independently (P < .01) associated with increased use of DNR
      orders included increasing age (odds ratio [OR], 1.06 per year); admission from a
      skilled nursing facility (OR, 2.44) or through the emergency department (OR,
      1.49); cancer (OR, 2.73), intracerebral hemorrhage (OR, 2.12), coma (OR, 7.47),
      or lethargy or stupor on admission neurological assessment (OR, 3.38); and
      increasing admission severity (OR; 1.29 per decile). In contrast, African
      American race was associated with lower use of DNR orders (OR, 0.54). Although
      substantial variation in the use of DNR orders was observed across hospitals,
      with rates ranging from 12% to 32%, adjusting for the above patient
      characteristics eliminated much of this variation, including differences between
      major teaching and other hospitals and between hospitals with and without
      religious affiliations. CONCLUSIONS: In our community-based analysis of patients
      with stroke, the use of DNR orders was common and was strongly related to several
      patient characteristics. These factors explained much of the variation across
      hospitals. While our analysis did not account for differences in patient
      preferences for treatment, the differences we observed in the use of DNR orders
      across sociodemographic groups are suggestive of variations in care and may have
      important implications for the cost and quality of hospital care.

PMID- 9290544
TI  - Cumulative glycemic exposure and microvascular complications in insulin-dependent
      diabetes mellitus. The glycemic threshold revisited.
AB  - BACKGROUND: The development of microvascular insulin-dependent diabetes mellitus
      (IDDM) complications has been shown to be related to both duration of diabetes
      and the degree of glycemic exposure. However, controversy exists as to whether
      there is a threshold of glycemic exposure, below which there is minimal risk.
      Furthermore, there are few data describing the relationship of total glycemic
      exposure (duration x degree) to complications rates-a potentially useful research
      and clinical tool. OBJECTIVES: To determine a cumulative glycemic exposure
      variable that combines the effect of both degree and duration of hyperglycemia
      and to evaluate this variable in terms of its relation to microvascular
      complications. The association between cumulative glycemic exposure and
      complication risk was also examined to evaluate whether there was a threshold
      effect. METHODS: A total of 353 patients with IDDM who had completed the first 6
      years of follow-up in the Pittsburgh Epidemiology of Diabetes Complications Study
      were included in this analysis. These subjects had a mean age of 27.9 years, and
      the mean duration of the disease was 19.4 years. Subjects were examined at
      baseline (cycle 1) and then biennially (cycle 2, cycle 3, and cycle 4) for
      diabetes complications. Total glycosylated hemoglobin (HbA1) was measured at each
      cycle. A cumulative glycemic exposure variable, named A1months, was calculated by
      multiplying the number of HbA1 units above normal at each cycle by the number of
      months between the midpoints of the preceding and succeeding cycle intervals.
      RESULTS: The mean number of A1months experienced at the time of diagnosis of
      proliferative retinopathy (914), microalbuminuria (952), overt nephropathy
      (1043), and distal symmetrical polyneuropathy (1043) did not vary by duration of
      diabetes. Thus, approximately 1000 A1months were needed (on average) for the
      advanced complications to develop. Although the risk for developing proliferative
      retinopathy rose gradually as A1months increased, a more abrupt increase in the
      risk was seen (again at approximately 1000 A1months) for microalbuminuria (odds
      ratio, 6.9; 95% confidence interval, 2.5-19.1), overt nephropathy (odds ratio,
      6.5; 95% confidence interval, 2.0-21.7), and distal symmetrical polyneuropathy
      (odds ratio, 6.5; 95% confidence interval, 2.4-17.8). Nonetheless, complications
      developed in the majority of cases at glycemic exposures below 1000 A1months. The
      cumulative glycemic exposure variable A1months does not predict complications any
      better than its component variables (duration and HbA1). Furthermore, formal
      statistical testing failed to show a definitive threshold for any complication.
      CONCLUSIONS: Although A1months does not enhance prediction of complications, it
      may be a useful summary measure of glycemic exposure for both patients and
      physicians. However, although subjects with 1000 A1months or more appear to be at
      increased risk of developing most microvascular complications, because the
      majority of complications arise in subjects with less than this exposure, this
      threshold value should only be considered a minimal goal. For example, our data
      suggest that for most microvascular complications to develop, it would take, on
      average, 83 years with an HbA1 unit at 1% above normal, 42 years at 2% above
      normal, 28 years at 3% above normal. 21 years at 4% above normal, and 18 years at
      5% above normal.

PMID- 9290545
TI  - Analysis of compassionate use itraconazole therapy for invasive aspergillosis by
      the NIAID Mycoses Study Group criteria.
AB  - BACKGROUND: Successful therapy of invasive aspergillosis is difficult, and the
      place of new drugs is evolving. Earlier studies, with fewer patients, suggest
      itraconazole, an oral azole, is effective for some patients. METHODS:
      Compassionate use data were analyzed by criteria applied previously in a
      multicenter trial as a reference point. The course of 125 patients was evaluated
      and their clinical settings and responses were categorized. RESULTS: Overall, 34
      (27%) had a complete response, 45 (36%) improved, 20 (16%) were unchanged, and 26
      (21%) worsened. The subset receiving less than 2 weeks of itraconazole therapy
      had a worse outcome than the remainder of the group as did patients with sinus,
      central nervous system, or widely disseminated disease. Prior therapy, age,
      underlying disease, other sites of aspergillosis, dose, or Aspergillus species
      did not correlate closely with outcome. In patients who responded, a period of
      months was commonly required before objective improvement was documented.
      Patients who underwent bone marrow transplantation fared better than in previous
      reports. CONCLUSIONS: Itraconazole is effective in many patients with
      aspergillosis. This large series supports earlier conclusions that response rates
      are similar to those reported for amphotericin B.

PMID- 9290546
TI  - Diagnosis and management of neurological sarcoidosis.
AB  - BACKGROUND: Neurological involvement is a significant cause of morbidity and
      mortality in patients with sarcoidosis. Detection and management of
      neurosarcoidosis remains problematic. Our interest in immunosuppressive agents
      for chronic sarcoidosis has given us experience with various agents for the
      treatment of sarcoidosis, including cyclophosphamide and methotrexate. METHODS:
      We analyzed all patients with sarcoidosis seen in our clinic during a 10-year
      period. Evaluation for neurological disease included routine physical
      examination. Magnetic resonance imaging, cerebral spinal fluid analysis, and
      neural tissue biopsy were performed where clinically indicated. Patients were
      treated with corticosteroids, methotrexate, or cyclophosphamide. RESULTS:
      Neurological disease was identified in 71 of 554 patients with sarcoidosis.
      Seventh (facial) cranial nerve paralysis was the most common manifestation
      identified in 39 patients. This included 24 patients with facial nerve palsy as
      the only manifestation of neurological sarcoidosis in whom complete recovery was
      seen in all but 1 patient. Forty-eight patients with disease other than facial
      nerve palsy received corticosteroids or other therapies. Corticosteroids
      benefited only 14 patients (29%). Methotrexate successfully treated 17 (61%) of
      28 patients and cyclophosphamide controlled disease in 9 (90%) of 10 assessable
      patients. Methotrexate and cyclophosphamide were each associated with a higher
      response rate than corticosteroids alone (chi 2, 14.6; P < .001). CONCLUSIONS:
      Neurological symptoms can be significant manifestations of sarcoidosis. Facial
      nerve paralysis is a common, but usually self-limited form of disease. Other
      manifestations are usually chronic and agents other than corticosteroids appear
      to have increased efficacy with lower morbidity.

PMID- 9290549
TI  - Spook house sporotrichosis. A point-source outbreak of sporotrichosis associated
      with hay bale props in a Halloween haunted-house.
AB  - While isolated cases of sporotrichosis typically occur following contact with
      contaminated plant materials, outbreaks are distinctly unusual. A temporal
      increase in the incidence of sporotrichosis in a dermatology practice at a
      military installation in southwestern Oklahoma prompted an investigation.
      Patients with sporotrichosis presenting to a single dermatologist in the winter
      of 1992-1993 were interviewed, epidemiological data were collected, and fungal
      cultures were obtained from incriminated hay fields. Five patients presented with
      cutaneous sporotrichosis during a 5-week period beginning in December 1992. Four
      patients had maintained hay bales in a Halloween haunted house and the fifth
      patient had visited the house once. As in 3 previous reports, this outbreak was
      associated with stored hay or hay bales harvested in the US plains states.
      Contact with hay should be recognized as a risk factor for infection with
      Sporothrix schenckii. Outbreaks are possible given adequate intensity of exposure
      and may be difficult to recognize because of the delayed presentation of clinical
      illness.

PMID- 9290548
TI  - Perioperative management of colon cancer under Medicare risk programs.
AB  - OBJECTIVE: To determine differences in perioperative care and outcomes for
      patients with colon cancer enrolled in Medicare health maintenance organizations
      compared with similar fee-for-service nonenrollees. METHODS: Cross-sectional
      evaluation of hospital care and posthospital outcomes with data obtained from
      medical records. Nineteen health maintenance organizations representing all model
      types were selected from 12 states. The nonenrollee sample was drawn from the
      same areas. The sample included 412 enrollees and 401 nonenrollees, representing
      65 hospitals for health maintenance organizations and 61 hospitals for fee-for
      service. RESULTS: Nonenrollees were slightly older and had higher preoperative
      risk. Enrollees had shorter intervals between admission and surgery (enrollees,
      1.55 days vs nonenrollees, 2.85 days). Differences in length of stay (enrollees,
      10.9 days vs nonenrollees, 14.2 days) persisted even after controlling for
      preoperative health status. Differences in admissions to intensive care units
      (enrollees, 36.4% vs nonenrollees, 44.4%) were highly influenced by preoperative
      health status. Nonenrollees were more significantly likely to receive
      preoperative antibiotics, postoperative testing (eg, postoperative chest
      radiographs and electrocardiograms), and postoperative patient-controlled
      analgesia. Tumor staging was similar for both groups. Enrollees were more likely
      to be discharged home, while nonenrollees were more likely to be discharged to a
      nursing home. There were no significant differences in hospital deaths or
      postdischarge readmissions. CONCLUSIONS: Health maintenance organization
      enrollees with colon cancer received less clinical services of several types than
      similar patients in fee-for-service settings, had shorter hospital stays, and
      were less likely to be discharged to nursing homes. However, there was no
      evidence that they experienced different outcomes.

PMID- 9290547
TI  - Haemophilus species bacteremia in adults. The importance of the human
      immunodeficiency virus epidemic.
AB  - BACKGROUND: Until the late 1970s, invasive infections caused by Haemophilus
      species were thought to occur mainly in children and only infrequently in adults.
      OBJECTIVE: To report the largest series to date of Haemophilus species bacteremia
      (HB) from a single center. DESIGN: Retrospective. SETTING: Large, tertiary care,
      general teaching hospital. METHODS: We reviewed the charts of adult patients with
      HB detected from January 1, 1986, to December 31, 1994. Haemophilus strains were
      serotyped, and the antimicrobial resistance pattern was analyzed. RESULTS: One
      hundred sixteen patients had HB (0.26 cases per 1000 admissions). Thirty-eight
      children and 16 adults were excluded. Human immunodeficiency virus (HIV)
      infection was the most common underlying condition (n = 18 [29%]), followed by
      malignant neoplasms (n = 12 [19%]) and chronic obstructive pulmonary disease (n =
      12 [19%]). Prevalence in HIV-positive patients was 5 cases per 1000 admissions vs
      0.2 cases per 1000 admissions in HIV-negative patients. Infection was nosocomial
      in 16 patients (26%). Focal diseases were pneumonia in 41 patients (66%),
      cholangitis in 5 patients (8%), endocarditis in 3 patients (5%), meningitis and
      septic arthritis each in 1 patient (2%), and primary bacteremia in 9 patients
      (14%). The HIV-positive patients were significantly younger and presented more
      frequently with pneumonia (P < .05). Overall, 14 patients died (22%). Bacteremia
      was polymicrobial in 11 patients (18%). Haemophilus influenzae was isolated in 53
      patients (85%). Rates of antimicrobial resistance were 11% to chloramphenicol
      sodium succinate, 48% to ampicillin sodium, 78% to erythromycin stearate, 76% to
      combined sulfamethoxazole and trimethoprim, 15% to rifampin, and 57% to
      clarithromycin. CONCLUSIONS: Infection with HIV has become the most common
      underlying disease in adults with HB in our hospital. Therapeutic approaches must
      take into account the high rate of antimicrobial resistance.

PMID- 9290551
TI  - Transmission of human immunodeficiency virus through saliva after a lip bite.

PMID- 9290550
TI  - Toxic shock-like syndrome caused by non-group A beta-hemolytic streptococci.
AB  - Two patients with rapidly developing shock, multisystem organ failure, and
      destructive soft-tissue infection caused by groups G and C streptococci are
      described. Both patients died rapidly despite aggressive treatment. The clinical
      characteristics cannot be distinguished from those of toxic shock-like syndrome,
      but Streptococcus pyogenes was not recovered. These strains did not produce any
      previously identified type of streptococcal pyrogenic exotoxins. These findings
      suggest that toxic shock-like syndrome can be caused not only by group A but also
      groups G and C streptococci. The causative strains of toxic shock-like syndrome
      may have something in common with unknown virulent factors for this syndrome.

PMID- 9290552
TI  - Preventing strokes associated with carotid endarterectomy: detection of
      embolisation by transcranial Doppler monitoring.

PMID- 9290553
TI  - Conversion from endoluminal to open repair of abdominal aortic aneurysms: a
      hazardous procedure.
AB  - AIM: The purpose of this study was to analyse the technical problems associated
      with conversion from endoluminal repair of abdominal aortic aneurysms (AAA) to
      open repair and document the outcome in patients with this clinical course.
      METHODS: Between May 1992 and May 1996 endoluminal repair of AAA was undertaken
      in 113 patients. Forty-eight of these had medical co-morbidities which led to
      them being rejected for open repair at other medical centres. Conversion from
      endoluminal to open repair was required in 18 patients. Thirteen of these
      occurred at the original operation (primary conversion) and five occurred at a
      later operation (secondary conversion). Seven of the 18 patients undergoing
      conversion had serious medical co-morbidities. Three different methods of open
      repair were used. The technique selected was determined by the cause of failure
      leading to conversion. Standard open AAA repair was used in patients requiring
      conversion for access problems (n = 2) and balloon malfunction, where the device
      ended up entirely within the aneurysmal sac (n = 1). Modifications to the
      standard technique were required in patients in which the endograft was correctly
      positioned immediately below the renal arteries and/or where part of the
      endograft was within one or both common iliac arteries (n = 11). Supra-coeliac
      control was required for patients with aortic rupture (n = 1), renal arteries
      covered by the endograft (n = 2) and situations where the delivery catheter was
      trapped within the aorta above a twisted bifurcated graft (n = 1). The mean
      volume of contrast used was 225 ml and the mean operative time was 5.25 h in
      patients undergoing primary conversion. RESULTS: Conversion to open repair was
      achieved in all 18 patients. Renal impairment requiring dialysis occurred in
      three patients. There were three perioperative deaths, all of which were
      procedure-related (17%), and one late death. All four deaths occurred from among
      the group of seven patients with preoperative co-morbidities. CONCLUSIONS:
      Converting an endoluminal to an open AAA repair may require modifications to the
      standard open technique and result in a much higher than generally accepted
      morbidity and mortality rate. Patients rejected for open repair because of co
      morbidities ran the same chance of requiring conversion as those without co
      morbidities (15-17%). If conversion was required, however, they stood a 3 in 7 or
      43% chance of dying.

PMID- 9290554
TI  - Serum-elastin-peptides as a predictor of expansion of small abdominal aortic
      aneurysms.
AB  - OBJECTIVE: To optimise the indication and time for operation for abdominal aortic
      aneurysm (AAA), we analysed whether or not serum-elastin-peptides (SEP) could be
      a potential predictor for expansion. MATERIALS AND METHODS: Four thousand, four
      hundred and four 65-73-year-old males were invited for screening to detect an
      AAA. Three thousand, three hundred and thirty-four attended (76%). One hundred
      and forty-one had AAA, and 19 > 5 cm in diameter were referred for immediate
      operation. The remaining 122 AAA were offered an annual follow-up. Ninety-nine
      were later asked for a blood-sample, 83 attended. SEP was determined using an
      ELISA-technique. The observer was blinded to the SEP result. RESULTS: The average
      expansion was 2.6 mm/year, and 10 (8.1) were referred for operation because of a
      diameter of > 5 cm. SEP were positively correlated to expansion (R = 0.4, F =
      14.65). In multiple regression analyses, AAA size, SEP, beta-agonist-treatment,
      and FEV1, but not beta-blockers, were predictors of expansion. SEP remained a
      relatively strong predictor (F = 13.13). CONCLUSIONS: Serum-elastin-peptides seem
      to predict expansion, but a larger, longer study is needed to establish clinical
      recommendations.

PMID- 9290555
TI  - Lipoprotein (a) and its relationship to risk factors and severity of
      atherosclerotic peripheral vascular disease.
AB  - OBJECTIVES: To determine the significance of Lipoprotein (a) (Lp(a)) as a risk
      factor for atherosclerotic lower limb peripheral vascular disease (PVD), and its
      relationship to other demographic and biochemical variables and disease pattern
      and severity. DESIGN: Prospective case-control study. MATERIAL AND METHODS:
      Demographic and biochemical risk factors, lipoprotein fractions and Lp(a) were
      measured in 200 patients with PVD and 200 age- and sex-matched control subjects.
      Lp(a) levels were correlated with traditional risk factors and clinical and
      vascular laboratory disease parameters. RESULTS: Patients with PVD have a higher
      incidence of smoking, hypertension, and diabetes mellitus; and had significantly
      higher levels of serum cholesterol, triglycerides, LDL, VLDL, apolipoprotein B,
      fasting glucose, fibrinogen, plasminogen, haematocrit, white cell and platelet
      counts; but lower levels of HDL and apolipoprotein A1. Fasting Lp (a)
      concentration is an independent risk factor for PVD and is significantly higher
      in the patients (median = 26.1 mg/dl [4.8-195], mean = 36.5 +/- 32.6 mg/dl) than
      in controls (median = 18.2 mg/dl [5.4-216], mean = 27.2 +/- 28.1 mg/dl; p <
      0.0001). In patients with PVD, Lp(a) correlated positively with plasma LDL,
      cholesterol, fibrinogen, renal disease, and apolipoprotein B. Fasting levels of >
      24 mg/dl incurred a two-fold increase in risk of PVD. Patients with a higher
      Lp(a) have a significantly higher incidence of resting pain and ulcerations, and
      regression analysis confirmed smoking and Lp(a) level to be associated with the
      SVS category of disease severity. CONCLUSIONS: Lipoprotein (a) is a significant
      independent risk factor for PVD. Lp(a) levels correlated with LDL, cholesterol,
      fibrinogen, apolipoprotein B and disease severity. An elevated Lp(a) level may be
      associated with more severe forms of PVD.

PMID- 9290558
TI  - Pre-bypass quality assessment of the long saphenous vein wall with ultrasound and
      histology.
AB  - OBJECTIVES: Pre-existing unsuspected wall changes in saphenous vein grafts have
      been implicated in the graft outcome. Pre-bypass assessment of the vein may
      identify grafts at high risk for failure. This study was conducted to evaluate
      preoperatively the quality of the long saphenous vein (LSV) wall with ultrasound
      and histology. DESIGN: Prospective clinical study. MATERIAL AND METHODS: Three
      particular LSV segments, ankle, knee and mid-thigh, were evaluated preoperatively
      by ultrasound in 40 limbs of 38 patients, candidates for coronary artery bypass
      grafting. The venous wall was characterised based on its thickness and
      echogenicity in three categories: normal, moderately and severely fibrotic. LSV
      specimens taken from the above sites were also grouped into the same three
      categories based on their fibrotic content found on histology. RESULTS: In total,
      89 vein specimens were evaluated. On ultrasound, 81 specimens were detected as
      normal (91%), seven as moderately (8%) and one as severely fibrotic (1%). On
      histology, only eight specimens were found normal (9%), 75 with moderate (84%)
      and six with severe fibrosis (7%). Similar wall characterisation with both
      examinations was found in only 19% (17/89) of the specimens. Eighty-one specimens
      (91%) had some degree of fibrosis on histology. Different grades of fibrosis were
      found on histology in different sites of the same vein. CONCLUSIONS: Pre-existing
      wall changes are very common in vein grafts used for bypass surgery. However, the
      ultrasonic characterisation of the venous wall preoperatively cannot reliably
      identify these changes.

PMID- 9290557
TI  - Myointimal hyperplasia in vein collars for ePTFE grafts.
AB  - OBJECTIVE: To understand the cause of intermediate ePTFE graft failure when a
      venous boot is used. This might give insight into the improvement in patency that
      results from the use of a venous boot. DESIGN: A histological and radiological
      study of failed and failing grafts. METHODS: A review of patients operated upon
      in St Mary's Hospital under the care of a single consultant. RESULTS: Four
      anastomoses were retrieved following irretrievable occlusion and found to have
      myointimal hyperplasia at the function between the ePTFE graft and collar. The
      artery was relatively spared. In a further six patients these results have been
      corroborated by angiography. CONCLUSIONS: Myointimal hyperplasia occurs at the
      interface between ePTFE and vein collar and the recipient artery is relatively
      spared. This manipulation of the site of myointimal hyperplasia may result in
      improved patency rates.

PMID- 9290556
TI  - The first 15 months of transluminal abdominal aortic aneurysm management: a
      single centre experience.
AB  - OBJECTIVES: To assess the early experience with the transfemorally placed modular
      endovascular MinTec graft (TPEG) for abdominal aortic aneurysm (AAA). DESIGN: One
      single centre prospective evaluation of the endograft procedure as well as early
      postoperative results. SETTING: An academic teaching hospital. PATIENTS: 30
      consecutive patients treated during a period of 15 months. RESULTS: Peri- and
      postoperative morbidity and mortality were evaluated according to the
      recommendations of the Ad Hoc Committee on Reporting Standards. The endograft
      procedure was successful in 28 patients (93.4%); two patients (6.6%) needed
      conversion into open conventional y-graft replacement; one patient died 36 days
      following intervention from multiple organ failure. Another patient died from
      pancreatitis unrelated to the implantation. Endoleaks were treated by
      "overstenting" or distal extension of the endografts, but conversions were
      unnecessary. Five severe adverse events were noted in four patients. CONCLUSIONS:
      TPEG is a feasible but technically demanding procedure, requiring both surgical
      techniques and catheter skills. The potential for less operative morbidity and
      simpler aneurysm management compared to conventional open surgery may be present.
      Close follow-up of patients is necessary to understand the development and
      treatment of endoleaks.

PMID- 9290559
TI  - Dilatation of saphenous vein grafts by nitric oxide.
AB  - OBJECTIVES: To investigate firstly whether flow-dependent vasodilation is
      maintained in vein grafts, and secondly whether nitric oxide donors dilate vein
      grafts to improve the flow through graft stenoses. DESIGN, MATERIALS AND METHODS:
      The vasodilatation of mature patent vein grafts, in response to reactive
      hyperaemia and glyceryl trinitrate (GTN), was assessed by the change in external
      diameter using duplex ultrasonography. The severity (ratio of proximal systolic
      velocity, V1, to peak systolic velocity at the stenosis, V2, of vein graft
      stenoses was determined by duplex ultrasonography before and after 24 h of local
      application of GTN patches. RESULTS: In post-occlusion hyperaemia the diameter of
      patent distal vein grafts (n = 7) increased to a maximum of 112 +/- 1.9% of
      resting diameter after 2 min, p = 0.026. The diameter increased further to 117 +/
      2.5% of the resting value 5 min after oral GTN (n = 5), p = 0.007. The velocity
      ratio, V2/V1, through graft stenoses (n = 6) decreased by 20 +/- 5% after
      application of GTN patches, principally as a result of reduction in V2, mean
      difference 0.8, p = 0.15. The changes in response to GTN were more evident for
      proximal than distal vein graft stenoses. CONCLUSION: Flow-induced vasodilatation
      responses, which have been attributed to the endothelial release of nitric oxide,
      are maintained in patent vein grafts: the grafts dilate even further in response
      to GTN. The application of GTN patches close to a vein graft stenoses appears to
      reduce the velocity ratio through vein graft stenoses. GTN patches might be used
      to reduce the risk of graft occlusion when there is a delay between the detection
      and the treatment of haemodynamically significant graft stenoses.

PMID- 9290560
TI  - Endovascular abdominal aortic aneurysm repair induces significant alterations in
      surface adhesion molecule expression on donor white blood cells exposed to
      patient plasma.
AB  - OBJECTIVE: To determine the response of white blood cells in endovascular aortic
      aneurysm repair. MATERIALS AND METHODS: Seven patients treated with an
      endoluminal procedure (AAA-E) and seven patients undergoing conventional surgery
      (AAA-C) were included (all males, aged 52-80 years). A panel of monoclonal
      antibodies against CD11a, CD11b, CD11c, CD18 and L-selectin was used. To
      determine the surface receptors on both circulating and sequestered white blood
      cells, plasma from the patients and cells from healthy donors were combined for
      flow-cytometry. RESULTS: The expression of CD11a adhesion molecules only showed
      slight variations regarding granulocytes, but was more pronounced on monocytes,
      however, without significant differences between the two patient groups, CD11b,
      CD11c and CD18 molecules on both granulocytes and monocytes were significantly
      upregulated 60 min after the endovascular procedure compared to conventional
      aneurysm repair, and L-selectin molecules were by this time correspondingly
      cleaved off. CONCLUSION: Endovascular aneurysm repair differed significantly from
      conventional aneurysm surgery with peak adhesion molecule expression 60 min after
      balloon deflation, probably caused by release of tumour necrosis factor-alpha
      (TNF-alpha).

PMID- 9290561
TI  - Patch angioplasty following carotid endarterectomy using the ipsilateral superior
      thyroid artery.
AB  - OBJECTIVES AND DESIGN: Synthetic and saphenous vein patches, when used in the
      carotid territory, are disadvantaged by complications. We tested the feasibility
      of using a locally harvested artery, the ipsilateral superior thyroid artery
      (STA), as a source of patching material following carotid endarterectomy (CEA).
      MATERIALS AND METHODS: Twenty-two consecutive patients (15 male) with a median
      age of 70 (range 53-82) years underwent CEA with an intention to use the STA for
      patch angioplasty. The STA was harvested via a standard carotid incision and
      opened longitudinally to fashion a patch. RESULTS: Of the 22 STAs harvested, only
      two were rejected due to small calibre. Mean harvesting time was 12 min and there
      were no immediate complications. Duplex scanning has not revealed restenosis
      (mean peak velocity = 0.78 [range 0.45-1.16] m/s) in any patient with a median
      follow-up of 13 (range 3-19) months. CONCLUSIONS: This technique is quick,
      convenient and obviates many of the disadvantages associated with conventional
      patches. Follow-up has shown the technique to be both efficacious and durable in
      the medium term.

PMID- 9290562
TI  - Midline extraperitoneal approach for elective abdominal aortic aneurysm repair.
AB  - The incidence of abdominal aortic aneurysms (AAA) is rising and elective repair
      is becoming more commonplace. We describe a new, simple midline extraperitoneal
      approach for AAA repair. It is particularly suitable for patients who have an
      inflammatory AAA, abdominal adhesions or a horseshoe kidney. This approach
      provides excellent exposure to the whole aortoiliac system without the need for
      separate incisions, whilst retaining the potential advantages of the
      extraperitoneal approach.

PMID- 9290563
TI  - Retroperitoneal endoscopic iliofemoral cross-over graft for critical limb
      ischaemia.

PMID- 9290564
TI  - Aneurysm of the inferior mesenteric artery: case report and review of the
      literature.

PMID- 9290565
TI  - Problems of abdominal aortic aneurysm associated with horseshoe kidney.

PMID- 9290566
TI  - Pathophysiological functions of ATP-sensitive K+ channels in myocardial ischemia.
AB  - The ATP-sensitive K+ channels (KATP) are characterized by strong inhibition by
      intracellular ATP but their activity is also modulated by various intra- and
      extracellular factors with complicated and undefined mechanism. These factors
      include a low concentration of ADP (or ATP/ADP ratio), a mildly low pH, G-protein
      coupled process, adenosine and so on. Intracellular ATP has a ligand action to
      inhibit the channel activity on the one hand, but on the other ATP is necessary
      for maintaining the channels in an operative state, probably due to the enzymatic
      process involving ATP hydrolysis. KATP is inhibited by antidiabetic sulfonylureas
      and sodium 5-hydroxydecanoate. The channels are activated by the K+ channel
      openers in an ATP-dependent manner, but may have diverse mechanisms of actions
      depending on different compounds. The KATP channel openings are responsible for
      shortening the action potential duration (APD) and partial K(+)-efflux during
      early ischemia. The discrepancy between the high sensitivity of intracellular ATP
      to inhibit KATP in cell-free, inside-out patches and millimolar orders of
      myocardial ATP concentration determined by the biochemical techniques may cast
      some doubts on the actual openings of this channel. It can be explained by the
      presence of cofactors to stimulate channel opening, heterogeneity or
      compartmentation of ATP distribution in the cell, the properties and high density
      of KATP, or a combination of these factors. The opening of KATP during ischemia
      may contribute to the development and aggravation of serious arrhythmias to some
      extent, but their opening also protects cellular damage, limits infarct size and
      improves recovery of cardiac function during reperfusion, acting as a
      cardioprotection mechanism. KATP opening may mimick the effects of ischemic
      preconditioning, but its effect may be variable among different animal species
      and experimental conditions. Further studies are necessary to clarify the actual
      role of channel opening and the molecular mechanism.

PMID- 9290567
TI  - Alterations of signal transduction system in heart failure.
AB  - Congestive heart failure (CHF) patients share several similar features, such as
      reduced cardiac contractility and neurohumoral activation to compensate the
      impaired cardiac function. In CHF patients, the cardiac renin-angitensin (RA)
      system, receptors, GTP-binding proteins, and their effector molecules are
      inevitably exposed to chronically elevated neurohumoral stimulation. A widely
      recognized concept is that a chronic increase in such stimulation can desensitize
      target cell receptors and the post-receptor signal transducing pathway. Recently,
      reports of several studies have indicated that the inhibitory GTP-binding protein
      (Gi) can be increased in CHF patients and animal models. Although direct evidence
      for a change in catalytic protein of adenylyl cyclase has not been found, limited
      information has suggested a reduced catalytic activity in terminally failing
      hearts. In this paper, we have assessed the changes in beta AR, GTP-binding
      protein, catalytic protein and beta ARK. We also examined angiotensinogen mRNA
      expression in failing heart. It was detected not only in the liver, but also in
      both the atrial and ventricular heart tissues, suggesting that angiotensinogen is
      synthesized in the human heart. Immunohistochemical studies revealed a stronger
      reaction in the endocardial layer of the human left ventricle than in the
      epicardial layer, and intense immunoreactivity in the conduction system and right
      atrium. Our experiments revealed a widespread immunopositive reaction for
      angiotensinogen in the left ventricle of diseased hearts. In the non-diseased
      heart, ACE and AT1 receptor RNA are present in ventricular muscles. Renin and Ao
      mRNA could not be detected in the subendocardium of non-diseased left ventricle,
      but both were present in the left ventricle of diseased hearts. These data
      indicate that the cardiac RA system plays an important role in the deterioration
      of cardiac function.

PMID- 9290569
TI  - Use of the body surface recovery time for detection of coronary artery disease.
AB  - We explored the relationship between body surface recovery time (RT), the
      interval between the QRS onset and the time of maximum derivative in the T-wave
      on a 16 precordial lead system electrocardiogram (ECG), and monophasic action
      potential (MAP) duration of the left ventricular endocardium in 9 patients in
      whom electrophysiologic testing was indicated. The usefulness of RT measurement
      on body surface ECG for the detection of coronary artery disease was evaluated in
      98 patients who had chest pain. The RT located in the right clavicular or upper
      sternal area showed a very high positive correlation (r = 0.91, p < 0.001) with
      MAP duration from the left ventricular endocardium and showed specific shortening
      in patients with one-vessel disease of the left anterior descending coronary
      artery. With a criterion of the RT located in the right clavicular or upper
      sternal area corrected by Bazett's formula < 380 msec1/2, a sensitivity of 81%
      and a specificity of 80% were achieved for detection of one-vessel disease of the
      left anterior descending coronary artery.

PMID- 9290568
TI  - Comparison of exercise stress testing with dobutamine stress echocardiography and
      exercise technetium-99m isonitrile single photon emission computerized tomography
      for diagnosis of coronary artery disease.
AB  - To compare the value of exercise electrocardiography with dobutamine stress
      echocardiography and exercise technetium-99m isonitrile single-photon emission
      computed tomography for coronary artery disease, 70 patients with either
      suspected or proven coronary artery disease underwent dobutamine stress
      echocardiography, exercise technetium-99m isonitrile single-photon emission
      computed tomography (mibi-SPECT) and treadmill exercise electrocardiography
      (ECG). Dobutamine echocardiography and exercise mibi-SPECT revealed a higher
      overall sensitivity than exercise testing (90 vs 57%, p < 0.001; 96 vs 57%, p <
      0.001, respectively). Dobutamine stress echocardiography showed a higher
      specificity than both exercise mibi-SPECT and treadmill exercise
      electrocardiography (90 vs 71%, p > 0.05; 90 and 62% p < 0.05, respectively) but
      the difference between dobutamine stress echocardiography and exercise mibi-SPECT
      was not statistically significant. Diagnostic accuracy of dobutamine stress
      echocardiography and exercise mibi-SPECT was higher than that of exercise testing
      (90 vs 59%, p < 0.001; 89 vs 59%, p < 0.001, respectively). Dobutamine stress
      echocardiography and exercise mibi-SPECT have superiority over exercise testing
      in the diagnosis of coronary artery disease and dobutamine stress
      echocardiography is an alternative for exercise mibi-SPECT.

PMID- 9290570
TI  - The ventricular gradient and altered ventricular activation patterns.
AB  - The ventricular gradient vector was determined in normal persons and in cases
      with left and right bundle branch block (BBB) by means of the best fit method
      from body surface potential mapping data. Similar measurements were also made in
      cases with artificial ventricular pacing and the G vector during sinus rhythm was
      compared with that of the paced beats. Results indicated that the magnitude of
      the G vector in cases with BBB was smaller than in normal persons. The
      directional change in the G vector was found to be along the direction of the QRS
      change in the majority of cases with left BBB. In right BBB, the direction of the
      G change was variable but the angle between the QRS change was less than 90
      degrees on average. Following right ventricular pacing a small increase of the G
      magnitude was observed acutely, which was opposite in direction to the QRS
      change. Possible mechanisms are discussed. The G changes in left and right BBB
      are considered to be based on certain chronic processes, different from those
      involved in the acute immediate effect of altered activation.

PMID- 9290571
TI  - Fusion with postpaced return cycle identical to tachycardia cycle length during
      transient entrainment of ventricular tachycardia and its implications.
AB  - In reentrant ventricular tachycardia (VT), the postpaced return cycle (RC) during
      transient entrainment at a pacing site far from the central common pathway is
      longer than the VT cycle length (VTCL), when VT is represented by a figure-eight
      model. However, the reentrant circuit has not been fully elucidated. The purpose
      of this study was to present VT in which the postpaced RC became identical to
      VTCL during transient entrainment while fusion is evident in the surface
      electrocardiogram (ECG). Among 38 patients with inducible reentrant VTs who
      underwent electrophysiologic study (EPS), 10 VTs of six patients were selected.
      All patients had underlying heart diseases: dilated cardiomyopathy (n = 2),
      coronary artery disease (n = 1), postoperative tetralogy of Fallot (TOF; n = 2),
      and arrhythmogenic right ventricular dysplasia (n = 1). Catheter mapping was
      performed to demonstrate that the site of origin was distant from the pacing
      site. The cycle length of induced VT (n = 10 VTs) was 380 +/- 41 msec. Five
      patients (83%) had two morphological VTs; one a left bundle branch block (LBBB)
      and the other a right bundle branch block (RBBB) pattern. During rapid pacing,
      constant fusion was observed in all VTs, but the postpaced RC was identical to
      VTCL. In 2 patients (4 VTs), the revolution of wavefronts around an anatomical
      obstacle (scar of myotomy in TOF, and infarction) was demonstrated. The fact that
      the postpaced RC was identical to VTCL but showed fusion in the surface ECG can
      be explained by macro-reentry. The pacing site must be located at the
      preferential route of the macroreentrant circuit.

PMID- 9290572
TI  - Safety and efficacy of oral flecainide acetate in patients with cardiac
      arrhythmias.
AB  - We retrospectively studied the clinical efficacy and safety of oral flecainide in
      38 patients with symptomatic arrhythmias. Patients received 100 to 200 mg daily
      of flecainide for a mean of 25 months (range 8 to 50 months). All patients had
      normal cardiac function. Paroxysmal atrial fibrillation (PAF) was observed in 29
      patients (76%). Other forms of arrhythmia included paroxysmal atrial flutter,
      seen in 3 patients (8%); premature atrial contraction and ventricular premature
      contraction, each seen in 2 patients (5%); and supraventricular tachycardia and
      ventricular tachycardia, each seen in 1 patient (3%). A complete response was
      obtained in 15 (52%) of 29 patients with PAF and a partial response in 8 patients
      (27%). The remaining 6 patients (21%) showed no response. A complete response was
      also obtained in 7 of 9 patients with other forms of arrhythmia. There were no
      differences in cardiac function and ECG parameters before and after treatment.
      Flecainide was withdrawn in 4 patients due to the development of
      electrocardiographic abnormalities. Three of these patients showed an atrial
      proarrhythmic effect. Abnormal ST elevations in the precordial leads were
      observed in 1 patient who received 200 mg of flecainide daily. In conclusion,
      flecainide was effective treatment for supraventricular and ventricular
      arrhythmias, but attention must be paid to the drug's potential proarrhythmic
      adverse effects.

PMID- 9290573
TI  - Increase in erythrocyte volume in patients with chronic atrial fibrillation.
AB  - Non-anemic macrocytosis is occasionally observed in patients with a history of
      alcoholism or chronic liver disease. Recently we reported that patients with
      atrial fibrillation (AF) had larger erythrocytes than normal subjects. In the
      present study, we examined the temporal changes in hematologic measurements
      during the development of AF in 88 male patients (chronic AF: 49, paroxysmal AF:
      39), and compared alcohol intake among the groups. The mean corpuscular volume of
      erythrocytes was significantly greater in chronic AF patients, both before (98.1
      +/- 6.1 (SD) fl p < 0.05) and after onset (within 6 months: 98.4 +/- 7.1 fl p <
      0.05; 1 year: 98.6 +/- 6.2 fl p < 0.01), compared with 300 age-matched male
      control subjects with sinus rhythm (95.9 +/- 3.6 fl). Hematocrit increased
      significantly with development of AF in both chronic and paroxysmal AF patients
      (p < 0.005). Mean daily alcohol consumption did not differ significantly among
      the control, chronic AF and paroxysmal AF groups. Our findings indicate that
      erythrocyte size is already larger in patients with chronic AF before the
      condition develops.

PMID- 9290574
TI  - Assessment of the accuracy of indirect blood pressure measurements.
AB  - This study assessed the accuracy of indirect blood pressure (BP) measurements by
      simultaneously performing three kinds of indirect BP measurement on the left arm
      (auscultatory, microphone and oscillometric methods) and a direct BP measurement
      on the left arm. The subjects were 34 hospitalized patients, ranging in age from
      18 to 73 years (average 47.5 years). Highly significant correlations in systolic
      or diastolic BP between a given pair of the three indirect methods. The indirect
      methods underestimated systolic BP and overestimated diastolic BP compared with
      the direct method, with differences of -12.2 +/- 10.5/+4.6 +/- 7.6
      (systolic/diastolic BP) with the oscillometric method, -8.1 +/- 9.7/+1.2 +/- 8.9
      with the microphone method and -10.6 +/- 8.1/+3.7 +/- 6.5 mmHg with the
      auscultatory method. The difference in systolic BP between the auscultatory and
      direct methods was greater and the difference in diastolic BP was smaller in
      subjects older than 50 years than in those aged 50 years or less (p < 0.001 for
      systolic BP, p < 0.05 for diastolic BP). The auscultatory method revealed greater
      systolic BP in subjects with increased carotid arterial wall stiffness assessed
      by echoarteriography. Thus, it is concluded that there are inherent differences
      in BP between the indirect and direct methods which can be attributed to the
      changes in arterial wall physical properties partly due to aging.

PMID- 9290575
TI  - An analysis of the effects of nitroglycerin on forearm circumference, with
      simultaneous recordings of arterial and venous diameters and blood pressure.
AB  - The aim of this study is to define the effect of sublingually administered
      nitroglycerin (NTG) on the diameters of the forearm arteries and veins as well as
      to define the relationship between these vascular changes and the forearm
      circumference in healthy volunteers. For this purpose, we employed a noninvasive
      method permitting the simultaneous quantitative recording of vascular diameters,
      forearm circumference and blood pressure using a miniature load cell, linear
      differential transformers and mercury-in-rubber strain gauge. Sublingually
      administered NTG (0.3 mg) increased the radial arterial diameter and the forearm
      circumference, whereas the cephalic vein capacitance was decreased; consequently,
      the cephalic vein acts to moderate the increase in forearm circumference. The
      results clearly indicate that nitroglycerin dilates forearm arteries but not
      forearm veins in the normal state.

PMID- 9290576
TI  - Essential pathway of reentry in the canine model of atrial flutter. Analysis
      using radiofrequency ablation.
AB  - In humans, the isthmus in the low right atrium between the tricuspid annulus and
      the inferior vena cava or the coronary sinus ostium is a well-established target
      of catheter ablation of common atrial flutter. In the canine model of atrial
      flutter with a Y-shaped incision, the tricuspid annulus was thought to constitute
      the essential reentrant pathway. The present study was designed to determine
      whether the supravalvular tissue around the tricuspid annulus is essential to
      atrial flutter in the canine model with an intercaval obstacle on the basis of
      the results of radiofrequency ablation. Epicardial approach of radiofrequency
      ablation was tested in 4 groups of dogs. Group A (5 dogs): Single application of
      radiofrequency energy (20 W) for 5 sec to the mid right atrial free wall. Group B
      (9 dogs): One to two applications to the tricuspid annulus. A ligature was also
      placed encircling the tricuspid annulus from the supravalvular atrial tissue to
      the subvalvular ventricular tissue. Group C (9 dogs): Linear transverse
      applications to the mid right atrial free wall between the tricuspid annulus and
      the intercaval obstacle. Group D (10 dogs): The isthmus between the inferior vena
      cava and the tricuspid annulus was ablated. After the experiment, the heart was
      excised for anatomical and histological studies. Atrial flutter was never
      abolished in all dogs in Groups A and B. A ligature encircling the tricuspid
      annulus also failed to terminate atrial flutter in 2 dogs tested. In contrast,
      atrial flutter was successfully abolished in 6 dogs (67%) of Group C and in 7
      dogs (70%) of Group D. Total energy delivered was significantly higher in Group C
      than in Group D (364 +/- 133 versus 139 +/- 65 joules, p < 0.003). The total
      energy required for successful ablation was related to the cross sectional area
      of the ablation site (r = 0.55, p < 0.05). These results indicate that the
      tricuspid annulus is not an essential part of the reentrant pathway in the canine
      model of atrial flutter with an intercaval obstacle. The entire atrial tissue
      between the anatomical barriers could be involved in the reentrant pathway, and
      should therefore be ablated transmurally for successful ablation.

PMID- 9290578
TI  - Differential distribution of ecNOS and iNOS mRNA in rat heart after endotoxin
      administration.
AB  - To evaluate the relationship between cardiovascular injury and the pathological
      significance of endothelial constitutive nitric oxide synthase (ecNOS) and
      inducible nitric oxide synthase (iNOS) in endotoxic shock, Wistar rats were
      injected intraperitoneally with 10 mg/kg Escherichia coli endotoxin and the
      resulting cardiovascular changes observed using immunohistochemistry,
      immunoelectron microscopy, the reverse transcription polymerase chain reaction
      (RT-PCR) and in situ hybridization at 4, 6, 8 and 10 h after endotoxin
      administration. Immunohistochemical and electron microscopic observations showed
      that ecNOS was localized in the cytoplasmic vesicles and rough endoplasmic
      reticulum of the endothelium of coronary arteries and intermyocardial capillaries
      in both control and endotoxin-treated rats. iNOS was localized in the cytoplasmic
      vesicles and endoplasmic reticulum of vascular endothelial cells, vascular smooth
      muscle cells and cardiomyocytes after endotoxin administration. The RT-PCR study
      confirmed the expression of ecNOS and iNOS mRNA in the heart tissues of all
      animals including controls. In situ hybridization showed that ecNOS mRNA was
      expressed in the cytoplasm of vascular endothelial cells in control and endotoxin
      treated rats. After endotoxin administration, iNOS mRNA was strongly expressed in
      vascular endothelial cells, vascular smooth muscle cells, cardiomyocytes and a
      small number of macrophages. Bacterial lipopoly-saccharide induces rapid release
      of nitric oxide in the microvasculature and cardiomyocytes resulting in the
      depression of cardiomyocyte contraction. These findings may describe the cardiac
      response after endotoxin treatment.

PMID- 9290577
TI  - Age-related effects of norepinephrine on rat ventricular hypertrophy.
AB  - Norepinephrine (NE) (2.5 micrograms/kg/min) was administered to 5-week-old male
      Sprague Dawley rats by subcutaneous osmotic mini pumps for 14 days to generate an
      in vivo cardiac hypertrophy model and the responses with respect to aging
      examined. In the model, ventricles were significantly hypertrophied without
      myocardial necrosis and without significant increases in heart rate or blood
      pressure; the beta adrenergic system was down-regulated. In 37-week-old rats
      receiving 1.0 microgram/kg/min NE, there was a tendency towards heart failure,
      and myocardial necrosis and interstitial fibrosis were revealed by histological
      examinations. The density of beta adrenergic receptors and adenylyl cyclase
      activity was lower in the older rats. The excess stimulation of adrenergic
      receptors caused severe cardiac injury in old rats regardless of down regulation
      of beta adrenergic receptors.

PMID- 9290579
TI  - Cardiac papillary fibroelastoma excision combined with reconstructive surgery.
AB  - Three cases of cardiac papillary fibroelastomas are described. Two-dimensional
      echocardiography detected the tumors in the mitral valve, the cordae tendinae and
      in the apex of the left ventricle--a unique location. The tumor excisions were
      combined with bypass operation, mitral valve reconstruction, repair of cordae
      tendinae and Maze-procedure. The three patients are doing well after surgery.

PMID- 9290580
TI  - Gene expression induced by cerebral ischemia: an apoptotic perspective.

PMID- 9290581
TI  - In vivo kinetics of [18F](N-methyl)benperidol: a novel PET tracer for assessment
      of dopaminergic D2-like receptor binding.
AB  - A novel D2-like receptor-binding radioligand, [18F](N-methyl)benperidol
      ([18F]NMB), was evaluated via positron emission tomographic (PET) imaging studies
      of baboons. [18F]NMB rapidly localized in vivo within dopaminergic receptor-rich
      cerebral tissues, and striatum-to-cerebellum ratios as high as 35 were achieved
      after 3 hours. Pretreatment of an animal with unlabeled receptor-specific
      antagonists before injection of [18F]NMB confirmed that the radioligand bound
      specifically to central D2-like receptors in vivo, and not to S2- or D1-like
      receptors. Unlabeled eticlopride displaced striatal [18F]NMB in vivo, showing
      that D2-like binding is reversible. Receptor-binding by the radioligand was
      resistant to competitive displacement by synaptic dopamine, as illustrated by the
      lack of effect of intravenous d-amphetamine on the in vivo localization of
      [18F]NMB. Studies involving sequential intravenous administration of [18F]NMB, d
      amphetamine, and eticlopride show that the radioligand does not undergo agonist
      mediated internalization with subsequent trapping. The feasibility of applying a
      three-compartment non-steady state model for quantification of [18F]NMB receptor
      binding was demonstrated. These in vivo characteristics give [18F]NMB distinct
      advantages over the PET radiopharmaceuticals currently used for clinical
      investigation of D2-like receptor binding.

PMID- 9290582
TI  - Immunoreactivity of cyclin D1/cdk4 in neurons and oligodendrocytes after focal
      cerebral ischemia in rat.
AB  - We investigated the expression of cyclin D1 and its kinase, cdk4, after induction
      of focal cerebral ischemia in the rat. Brain from rats (n = 6) subjected to 2
      hours of transient middle cerebral artery occlusion and 46 hours of reperfusion,
      and control sham-operated (n = 3) and normal (n = 2) rats were processed for dual
      label immunohistochemical study for cellular identification of the expression of
      these cell cycle proteins. Antibodies raised against microtubule-associated
      protein 2 and neuronal specific enolase for neurons, glial fibrillary acidic
      protein for astrocytes, myelin basic protein for oligodendrocytes and lectin
      histochemical study with the B4-isolectin for microglia were used for cell type
      identification. Double staining for DNA fragmentation detection (TUNEL) and
      expression of cyclin D1 and cdk4 also was performed. Cyclin D1 and cdk4 were
      selectively expressed in morphologically intact or altered neurons and
      oligodendrocytes localized to the ischemic tissue. Apoptotic cells were not
      immunoreactive to cyclin D1 and cdk4 at 46 hours after 2 hours of middle cerebral
      artery occlusion. The selective expression of cell cycle proteins observed in
      nonapoptotic ischemic postmitotic neurons and oligodendrocytes suggests a role
      for these proteins in cell survival after transient focal cerebral ischemia.

PMID- 9290583
TI  - Reduction of infarct volume by halothane: effect on cerebral blood flow or
      perifocal spreading depression-like depolarizations.
AB  - Halothane is a strong inhibitor of potassium evoked spreading depression (SD) in
      cats. In the current study, we investigate halothane effects on induction of
      perifocal SD-like depolarizations, CBF, and infarct evolution in focal ischemia.
      Calomel and platinum electrodes measured cortical direct current potential and
      CBF in ectosylvian, suprasylvian, and marginal gyri. Left middle cerebral artery
      occlusion (MCAO) induced permanent focal ischemia for 16 hours in artificially
      ventilated cats (30% oxygen, 70% nitrous oxide) under halothane (0.75%, n = 8) or
      alpha-chloralose anesthesia (60 mg/kg intravenously, n = 7). Under alpha
      chloralose, MCAO induced severe ischemia in ectosylvian and suprasylvian
      gyri(mean CBF < 10 mL/100 g/min), and direct current potentials turned
      immediately into terminal depolarization. In marginal gyri, CBF reduction was
      mild (more than 20 mL/100 g/min), and in six of seven animals, frequent SD-like
      depolarizations turned into terminal depolarization at a later stage of the
      experiments. Under halothane, MCAO induced severe ischemia (less than 10 mL/100
      g/min) and immediate terminal depolarization only in ectosylvian gyrus. In
      suprasylvian gyrus, residual CBF remained significantly higher (more than 10
      mL/100 g/min) than under alpha-chloralose, whereas in marginal gyri, CBF did not
      differ between groups. Compared with chloralose, the number of transient
      depolarizations was significantly reduced in marginal gyrus, and in suprasylvian
      gyrus transient but significantly longer depolarizations than in marginal gyrus
      were recorded. Except for one animal, transient depolarizations did not turn into
      terminal depolarization under halothane, and infarct volume reduction was
      particularly seen in suprasylvian gyrus. We conclude that halothane, the most
      commonly used anesthetic in studies of experimental brain ischemia, has
      protective properties, which may depend on both cerebrovascular and
      electrophysiologic influences.

PMID- 9290584
TI  - Assessment of cerebral blood flow and CO2 reactivity after controlled cortical
      impact by perfusion magnetic resonance imaging using arterial spin-labeling in
      rats.
AB  - We measured CBF and CO2 reactivity after traumatic brain injury (TBI) produced by
      controlled cortical impact (CCI) using magnetic resonance imaging (MRI) and spin
      labeled carotid artery water protons as an endogenous tracer. Fourteen Sprague
      Dawley rats divided into TBI (CCI; 4.02 +/- 0.14 m/s velocity; 2.5 mm
      deformation), sham, and control groups were studied 24 hours after TBI or
      surgery. Perfusion maps were generated during normocarbia (Paco2 30 to 40 mm Hg)
      and hypocarbia (PaCO2 15 to 25 mm Hg). During normocarbia, CBF was reduced within
      a cortical region of interest (ROI, injured versus contralateral) after TBI (200
      +/- 82 versus 296 +/- 65 mL.100 g-1.min-1, P < 0.05). Within a contusion-enriched
      ROI, CBF was reduced after TBI (142 +/- 73 versus 280 +/- 64 mL.100 g-1.min-1, P
      < 0.05). Cerebral blood flow in the sham group was modestly reduced (212 +/- 112
      versus 262 +/- 118 mL.100 g-1.min-1, P < 0.05). Also, TBI widened the
      distribution of CBF in injured and contralateral cortex. Hypocarbia reduced
      cortical CBF in control (48%), sham (45%), and TBI rats (48%) versus normocarbia,
      P < 0.05. In the contusion-enriched ROI, only controls showed a significant
      reduction in CBF, suggesting blunted CO2 reactivity in the sham and TBI group.
      CO2 reactivity was reduced in the sham (13%) and TBI (30%) groups within the
      cortical ROI (versus contralateral cortex). These values were increased twofold
      within the contusion-enriched ROI but were not statistically significant. After
      TBI, hypocarbia narrowed the CBF distribution in the injured cortex. We conclude
      that perfusion MRI using arterial spin-labeling is feasible for the serial,
      noninvasive measurement of CBF and CO2 reactivity in rats.

PMID- 9290585
TI  - Neuroprotective properties of the benzodiazepine receptor, partial agonist PNU
      101017 in the gerbil forebrain ischemia model.
AB  - PNU-101017 is a novel, imidazoquinoline amide and benzodiazepine receptor partial
      agonist that has high affinity for the GABAA receptor subtypes containing the
      alpha 1 and alpha 3 or alpha 5 subunits. At each of these receptors, the compound
      is a partial agonist with approximately 50% of the intrinsic activity of the full
      agonist diazepam. In view of the previously demonstrated anti-ischemic effects of
      some GABA agonists, the purpose of this study was to determine the ability of PNU
      101017 to salvage selectively vulnerable neuronal populations in the gerbil
      forebrain ischemia model. In an initial set of experiments, male gerbils were
      pretreated 30 minutes before ischemia induction (5 minutes) with PNU-101017 (3,
      10, or 30 mg/kg intraperitoneally) and again 2 hours after reperfusion. In
      vehicle (0.05 N HC1)-treated gerbils, the loss of hippocampal CA1 neurons at 5
      days was 80%. PNU-101017 was shown to produce a dose-related increase in CA1
      neuronal survival; at either 10 or 30 mg/kg, the loss of CA1 neurons was only 21%
      (P < 0.005 versus vehicle). A second experiment, examined the therapeutic window
      for PNU-101017 using the dose level of 30 mg/kg intraperitoneally. Administration
      of the first of two doses (2 hours apart) at the time of reperfusion resulted in
      an identical decrease in CA1 damage at 5 days to that seen with preischemic
      treatment (P < 0.003 versus vehicle). Even with a delay of the initial dosing
      until 4 hours after reperfusion, PNU-101017 reduced CA1 neuronal loss to only 32%
      (P < 0.01 versus vehicle). In a third experiment in which the duration of the
      ischemic insult was increased to 10 minutes and the brains were not analyzed
      until 28 days after ischemia, daily PNU-101017 dosing for the full 28 days still
      significantly preserved CA1 neurons, although less effectively than in the milder
      5 minute-ischemia model. The loss of dopaminergic nigrostriatal neurons was also
      reduced. The neuroprotective effect of PNU-101017 was not associated with any
      overt CNS depression and it did not correlate with hypothermia. This
      benzodiazepine-receptor partial agonist may have potential for the treatment of
      global cerebral ischemia.

PMID- 9290586
TI  - Morphologic evidence for L-citrulline conversion to L-arginine via the
      argininosuccinate pathway in porcine cerebral perivascular nerves.
AB  - Results from biochemical and pharmacologic studies suggest that Lcitrulline is
      taken up by cerebral perivascular nerves and is converted to Larginine for
      synthesizing nitric oxide (NO). The current study was designed using morphologic
      techniques to determine whether Lcitrulline is taken up into axoplasm of
      perivascular nerves and to explore the possibility that conversion of Lcitrulline
      to Larginine in these nerves is through the argininosuccinate pathway in porcine
      cerebral arteries. Results from light and electron microscopic autoradiographic
      studies indicated that dense silver grains representing L-[3H] citrulline uptake
      were found in cytoplasm of perivascular nerves, smooth muscle cells, and
      endothelial cells. The neuronal silver grains were significantly decreased in
      arteries pretreated with glutamine, which has been shown biochemically to block
      neuronal uptake of Lcitrulline. Results from light and electron microscopic
      immunohistochemical and histochemical studies indicate that dense nitric oxide
      synthase-immunoreactive (NOS-I), argininosuccinate synthetase-immunoreactive (ASS
      I), and argininosuccinate lyase-immunoreactive (ASL-I) fibers were found in the
      adventitia of cerebral arteries. NOS-, ASS-, and ASL-immunoreactivities fibers
      were found in the axoplasm and in the endothelium. In whole-mount preparations,
      the NOS-I, ASS-I, and ASL-I fibers were completely coincident with NADPH
      diaphorase fibers, suggesting that axoplasmic ASS, ASL, and NOS were co-localized
      in the same neurons. These studies provide the first morphologic evidence
      indicating that Lcitrulline is taken up into cytoplasm of cerebral perivascular
      nerves and that the axoplasmic enzymes catalyzing the conversion of Lcitrulline
      to Larginine (for synthesizing NO) by argininosuccinate pathway always are co
      localized in same neurons. These results support the hypothesis that Lcitrulline,
      the by-product of NO synthesis, is recycled to form Larginine for synthesizing NO
      in perivascular nerves to mediate cerebral neurogenic vasodilation. Results of
      the current morphologic studies also support the presence of Lcitrulline
      Larginine cycle in cerebral vascular endothelium.

PMID- 9290587
TI  - Astroglial and vascular interactions of noradrenaline terminals in the rat
      cerebral cortex.
AB  - Noradrenaline (NA) has been shown to influence astrocytic and vascular functions
      related to brain homeostasis, metabolism, local blood flow, and blood-brain
      barrier permeability. In the current study, we investigate the possible
      associations that exist between NA-immunoreactive nerve terminals and astrocytes
      and intraparenchymal blood vessels in the rat frontoparietal cortex, both at the
      light and electron microscopic levels. As a second step, we sought to determine
      whether the NA innervation around intracortical microvessels arises from
      peripheral or central structures by means of injections of N-(2-chloroethyl-N
      ethyl-2-bromobenzylamine) (DSP-4), a neurotoxin that specifically destroys NA
      neurons from the locus ceruleus. At the light microscopic level, 6.8% of all NA
      immunoreactive nerve terminals in the frontoparietal cortex were associated with
      vascular walls, and this perivascular noradrenergic input, together with that of
      the cerebral cortex, almost completely disappeared after DSP-4 administration.
      When analyzed at the ultrastructural level in control rats, NA terminals in the
      neuropil had a mean surface area of 0.53 +/- 0.03 micron2 and were rarely
      junctional (synaptic incidence close to 7%). Perivascular terminals (located
      within a 3-micron perimeter from the vessel basal lamina) counted at the electron
      microscopic level represented 8.8% of the total NA terminals in the cortical
      tissue. They were smaller (0.29 +/- 0.01 micron2, P < 0.05) than their neuronal
      counterparts and were located, on average, 1.34 +/- 0.08 microns away from
      intracortical blood vessels, which consisted mostly of capillaries (65%). None of
      the perivascular NA terminals engaged in junctional contacts with surrounding
      neuronal or vascular elements. The primary targets of both neuronal and
      perivascular NA nerve terminals consisted of dendrites, nerve terminals,
      astrocytes, and axons, whereas in the immediate vicinity (0.25 micron or less) of
      the microvessels, astrocytic processes represented the major target. The results
      of the current study show that penetrating arteries and intracortical
      microvessels receive a central NA input, albeit parasynaptic in its interaction,
      originating from the locus ceruleus. Particularly, they point to frequent
      appositions between both neuronal and perivascular NA terminals and astroglial
      cells and their processes. Such NA neuronal-glial and neuronal-glial-vascular
      associations could be of significance in the regulation of local metabolic and
      vascular functions under normal and pathologic situations.

PMID- 9290588
TI  - A theoretical model of cerebral hemodynamics: application to the study of
      arteriovenous malformations.
AB  - A comprehensive computer model of the cerebral circulation, based on both
      hydrodynamics and electrical network analysis, was used to investigate the
      influences of arteriovenous malformations (AVM) on regional cerebral
      hemodynamics. The basic model contained 114 normal compartments: 55 arteries, 37
      veins, 20 microvessel groups (MVG), one compartment representing systemic and
      extracranial vascular resistance, and one representing the heart. Each
      microvessel group, which represented the arteriolar bed, consisted of 5000
      microvessels. Cerebral blood flow autoregulation was simulated by a formula that
      determined the resistance and therefore the flow rate of the microvessel groups
      (arterioles) as a function of perfusion pressure. Elasticity was introduced to
      describe the compliance of each vessel. Flow rate was made a controlling factor
      for the positive regulation of the diameters of conductance vessels by
      calculation of shear stress on the vessel wall (vessel dilation). Models
      containing an AVM were constructed by adding an AVM compartment and its feeding
      arteries and draining veins. In addition to the basic model, AVM models were
      simulated with and without autoregulation and flow-induced conductance vessel
      dilation to evaluate the contributions of these factors on cerebral hemodynamics.
      Results for the model with vessel dilation were more similar to clinical
      observations than those without vessel dilation. Even in the presence of total
      vasoparalysis of the arteriolar bed equivalent, obliteration of a large (1000
      mL/min) shunt flow AVM resulted in a near-field CBF increase from a baseline of
      21 to a post-occlusion value of no more than 74 mL/100 g/min, casting doubt on a
      purely hemodynamic basis for severe hyperemia after treatment. The results of the
      simulations suggest that our model may be a useful tool to study hemodynamic
      problems of the cerebral circulation.

PMID- 9290589
TI  - Re: Standardization of ethics education and the use of the Hippocratic Oath for
      health science students.

PMID- 9290590
TI  - A primer on competency-based evaluation.

PMID- 9290591
TI  - Geriatric patient simulations for dental hygiene.
AB  - The rapidly increasing number of this country's elderly requires that dental
      hygiene students practice the clinical problem-solving skills of information
      gathering, assessment, and treatment applied to geriatric patients. Computer
      based simulations are purported to provide this experience, but little research
      has been completed with simulations in the education of dental hygienists. This
      paper summarizes the process used to design, develop, and evaluate a series of
      eighteen computer-based geriatric simulated patients. It contains a brief
      description of the simulations and a description of the design, validation,
      authoring, and formative evaluation phases. The paper also describes the
      summative evaluation, provides implementation suggestions, and summarizes future
      directions. The summative evaluation, conducted at four institutions, suggests
      that computer-based simulations are an effective instructional method as measured
      by pre/post-tests. The results suggest that simulations can provide a
      standardized set of geriatric patient experiences. These simulations may prove
      especially valuable at institutions that are unable to provide clinical geriatric
      experiences or lack the expertise to conduct a didactic course in geriatrics.

PMID- 9290592
TI  - Academic and clinical ramifications of integrity and cheating.

PMID- 9290593
TI  - Academic integrity: what kind of students are we getting, and how do we handle
      them once we get them?

PMID- 9290594
TI  - Academic corrective action from a legal perspective.

PMID- 9290595
TI  - Academic integrity from a student's perspective.

PMID- 9290596
TI  - Neonatal hypoglycemia: how low is too low?

PMID- 9290597
TI  - Functional effects of increasing omega-3 fatty acid intake.

PMID- 9290598
TI  - The newborn infant with leukemia.

PMID- 9290599
TI  - Onion skin and functionality in congenital heart disease.

PMID- 9290600
TI  - Are the ear and the heart fellow travelers of a sort?

PMID- 9290602
TI  - Ehrlichiosis in children.

PMID- 9290601
TI  - The metabolic crisis: a diagnostic challenge [editoria; comment].

PMID- 9290603
TI  - Insulin-like growth factor binding protein-1 levels in the diagnosis of
      hypoglycemia caused by hyperinsulinism.
AB  - The diagnosis of hypoglycemia caused by hyperinsulinism may be difficult because
      insulin levels are not uniformly elevated at the time of hypoglycemia. Insulin
      like growth factor binding protein-1 (IGFBP-1) is a 28 kd protein whose secretion
      is acutely inhibited by insulin. We hypothesized that serum levels of IGFBP-1
      would be a useful marker of hyperinsulinism. We measured IGFBP-1 levels during
      the course of standardized fasting studies in hospitalized children; 36 patients
      became hypoglycemic during the fasting studies, and samples obtained at the point
      of hypoglycemia were analyzed. On the basis of the currently used diagnostic
      criteria, 13 children had hyperinsulinism, 16 had ketotic hypoglycemia or no
      disorder, 3 had hypopituitarism or isolated growth hormone deficiency, 2 had
      glycogen storage disease type 1 and 2 had fatty acid oxidation disorders. In
      control subjects (children with ketotic hypoglycemia or no disorder), IGFBP-1
      levels rose during fasting to a mean of 343.8 +/- 71.3 ng/ml in the sample drawn
      at the time of hypoglycemia. Mean IGFBP-1 levels at hypoglycemia for the entire
      group with hyperinsulinism were 52.4 +/- 11.5 ng/ml, significantly different from
      levels seen in control subjects (p < 0.0001). In children with moderately
      controlled hyperinsulinism (fasting tolerance > 4 hours), mean IGFBP-1 levels at
      the time of hypoglycemia were 71.5 +/- 16.9 ng/ml. IGFBP-1 levels in the children
      with poorly controlled hyperinsulinism (fasting tolerance < 4 hours) failed to
      rise during fasting, with a mean of 30.1 +/- 10.4 ng/ml in the final sample.
      IGFBP-1 levels were inversely correlated with serum insulin and C-peptide levels
      (r = -0.71 and -0.72, respectively; p < 0.0001). Patients with other
      endocrinologic or metabolic diseases that result in fasting hypoglycemia
      demonstrated a rise in IGFBP-1 levels similar to that seen in ketotic
      hypoglycemia. Low serum levels of IGFBP-1 at the time of hypoglycemia provide an
      additional marker of insulin action that might help to differentiate
      hyperinsulinism from other hypoglycemic disorders.

PMID- 9290604
TI  - Effect of dietary linoleic/alpha-linolenic acid ratio on growth and visual
      function of term infants.
AB  - OBJECTIVES: To determine the effect of alpha-linolenic acid (ALA) intake (or the
      dietary linoleic acid [LA]/ALA ratio) on the growth and visual function of term
      infants. STUDY DESIGN: Normal term infants were assigned randomly and in masked
      fashion at birth to receive formulas with approximately 16% of total fatty acids
      as LA and 0.4%, 1.0%, 1.7%, or 3.2% of fatty acids as ALA (LA/ALA ratios of 44,
      18.2, 9.7, and 4.8) for the first 4 months of life. The fatty acid pattern of
      plasma phospholipids was determined shortly after birth and at approximately 21,
      60, and 120 days of age. Anthropometric data were obtained at the same times and
      also at approximately 240 days of age. Transient visual evoked responses (VERs)
      were measured at approximately 120 and 240 days of age. For comparisons,
      anthropometric and VER data also were obtained in infants who were exclusively
      breast-fed for the first 4 months of life. RESULTS: Infants who received the
      formula with 3.2% ALA (LA/ALA ratio, 4.8) had higher plasma concentrations of
      phospholipid docosahexaenoic acid (DHA) but lower concentrations of arachidonic
      acid at 21, 60, and 120 days of age. Mean weight of this group at 120 days of age
      was 760 gm less (p < 0.05) than the mean weight of the group that received the
      formula with 0.4% ALA (LA/ALA ratio, 44). Despite differences in plasma
      phospholipid DHA contents among groups, neither VER latency nor amplitude
      differed significantly among formula groups or between any formula group and age
      matched, breast-fed infants. CONCLUSIONS: The highest versus the lowest ALA
      intake (or the lowest vs the highest LA/ALA ratio) resulted in higher plasma
      phospholipid DHA content from 21 to 120 days of age but was not associated with
      improved visual function as assessed by transient VER. Moreover, mean body weight
      of infants who received the highest versus lowest ALA intake was less at 120 days
      (p < 0.05). These data suggest that the lower LA/ALA ratios currently recommended
      for infant formulas should not be adopted until the effect of such ratios on
      growth are evaluated more completely.

PMID- 9290605
TI  - Excessive anaerobic metabolism during exercise after repair of aortic
      coarctation.
AB  - OBJECTIVES: To determine whether survivors of surgery for coarctation of the
      aorta (CoA) have an excessive reliance on anaerobic metabolism during exercise.
      BACKGROUND: Patients with peripheral vascular disease cannot increase blood flow
      to their muscles normally during exercise. Consequently they acquire an early,
      excessive reliance on anaerobic metabolism and have depression of the ventilatory
      anaerobic threshold (VAT) and of the slope of the oxygen consumption-work rate
      relationship (delta VO2/delta WR). We speculated that the capacity to augment
      blood flow to the lower extremities during exercise may be impaired after CoA
      surgery and would result in similar metabolic disturbances. STUDY DESIGN:
      Progressive exercise tests were performed on 15 patients (ages 19 +/- 7 years;
      range, 10 to 32) after successful repair of CoA (residual resting gradient, 7.7
      +/- 7.1 mm Hg; range, 0 to 18), 15 age- and sex-matched healthy control subjects,
      and 10 patients (ages 13 +/- 3 years; range, 10 to 20) who had undergone ligation
      of a patent ductus arteriosus. RESULTS: The CoA patients' VAT averaged 14.8 +/-
      3.8 ml O2/kg per minute versus 19.3 +/- 3.1 ml O2/kg per minute for the control
      subjects (p < 0.01), and their delta VO2/delta WR averaged 8.2 +/- 1.8 ml/watt
      compared with 10.1 +/- 1.4 ml/watt for control subjects (p < 0.01). Furthermore,
      10 of 15 CoA patients had a VAT of less than 40% of predicted maximal oxygen
      consumption, and 9 of 16 had a delta VO2/delta WR of less than 8.7 ml O2/watt
      (generally accepted abnormal values). Patients with patent ductus arteriosus
      resembled the healthy control subjects with regard to anaerobic metabolism during
      exercise. CONCLUSIONS: Patients who have had CoA repairs commonly manifest an
      excessive reliance on anaerobic metabolism during exercise. This phenomenon may
      result from persistent blood flow abnormalities across the aortic arch during
      exercise, which may be present even after apparently successful surgery.

PMID- 9290606
TI  - Conotruncal cardiac anomalies and otitis media.
AB  - BACKGROUND: The neural crest influences the differentiation of the branchial
      arches, including the precursor tissue of the cardiac outflow tract and the
      eustachian tubes. Abnormal eustachian tubes are associated with otitis media. We
      hypothesized a relationship between conotruncal anomalies and eustachian tube
      anomalies. METHODS: We surveyed 115 nonsyndromic patients, aged 5 to 20 years,
      attending a state-run pediatric cardiology clinic. The cardiac anomalies were
      conotruncal (transposition of the great arteries, tetralogy of Fallot, or aortic
      stenosis) or nonconotruncal (atrial septal defect, tricuspid atresia,
      atrioventricular canal). Tympanic membrane photographs were categorized
      independently by two physicians as to normal, abnormal (scarred or other
      indication of otitis proneness), or indeterminate. RESULTS: For the 37 patients
      who had both ears categorized as normal or abnormal by both physicians, 20 of the
      26 with a conotruncal anomaly had evidence of otitis media. In contrast, only 4
      of 11 with nonconotruncal cardiac anomaly had evidence of otitis (p < 0.03;
      relative risk [conotruncal vs nonconotruncal], 5.83; 95% confidence interval,
      1.26 to 26.95). CONCLUSION: The concept is supported that a neural crest
      determined branchial field defect influences the development of the cardiac
      outflow tract and the eustachian tubes. Children with congenital cardiac
      conotruncal anomalies are otitis media prone.

PMID- 9290608
TI  - Plasma L-arginine concentrations in premature infants with necrotizing
      enterocolitis.
AB  - OBJECTIVE: To determine whether L-arginine concentrations (the substrate for
      nitric oxide synthesis) are lower in premature infants in whom necrotizing
      enterocolitis (NEC) develops than in unaffected infants. METHODS: We measured
      arginine and nutritional intake, plasma arginine, glutamine, total amino acids,
      and ammonia concentrations in 53 premature infants (mean gestational age +/- SD:
      27 +/- 1.7 weeks) at risk of NEC. Measurements were done on days 3, 7, 14 and 21
      and just before treatment in infants with NEC. RESULTS: Necrotizing enterocolitis
      developed in 11 infants between postnatal days 1 and 26. On day 3, plasma
      arginine concentrations were decreased compared with normal published values
      (mean +/- SE, 41 mumol/L +/- 4). Arginine concentrations increased with day of
      life of measurement (p < 0.001) and arginine intake (p < 0.001). Plasma arginine
      concentrations were significantly lower at the time of diagnosis in infants with
      NEC compared with control subjects, even after adjusting for arginine intake and
      day of life (p = 0.032). Plasma glutamine and total amino acid concentrations
      were not significantly different in infants with NEC compared with control
      subjects. Plasma ammonia concentrations were elevated on day 3 (mean +/- SE, 72
      +/- 3.3 mumol/L) and decreased with postnatal age (p < 0.001) and increasing
      plasma arginine concentrations (p < 0.001). CONCLUSION: Plasma arginine
      concentrations are decreased at the time of diagnosis in premature infants with
      NEC. The potential benefit of arginine supplementation in the prevention of the
      disease deserves evaluation.

PMID- 9290607
TI  - Mitochondrial carnitine-acylcarnitine translocase deficiency presenting as sudden
      neonatal death.
AB  - A breast-fed female infant died suddenly in the neonatal period at 31 hours of
      age with profound macrovesicular fatty infiltration of liver, kidney, and muscle
      on postmortem examination, suggestive of a defect in fatty acid beta-oxidation.
      Fatty acid and palmitoyl-carnitine oxidation studies and direct enzyme study of
      cultured skin fibroblasts suggested a deficiency in the oxidation of long-chain
      fatty acids distal to carnitine palmitoyl-transferase I and before long-chain
      acyl-coenzyme A dehydrogenases. Deficient activity of carnitine-acylcarnitine
      translocase was demonstrated with intermediate levels of activity in the infant's
      parents, consistent with autosomal recessive inheritance. Fatty acid oxidation
      studies showed deficient oxidation of fatty acids at all chain lengths from C10:0
      to C24:0, with partially reduced oxidation of C26:0 fatty acid, indicating the
      occurrence of a single mitochondrial carnitine-acylcarnitine translocase and
      demonstrating the requirement in vivo for L-carnitine for mitochondrial transport
      of all medium- and long-chain fatty acyl moieties. The disorder may have been
      precipitated in this breast-fed infant by poor initial feeding, fasting stress,
      and the long-chain triglycerides of human milk. The severity of the disorder
      prompted prenatal diagnosis, and affected siblings were excluded in two
      subsequent pregnancies by fatty acid oxidation in cultured chorionic villus cells
      and amniocytes.

PMID- 9290609
TI  - Sensitivity and specificity of the neonatal brain-stem auditory evoked potential
      for hearing and language deficits in survivors of extracorporeal membrane
      oxygenation.
AB  - OBJECTIVE: We determined the sensitivity and specificity of neonatal brain-stem
      auditory evoked potentials (BAEP) as markers for subsequent hearing impairment
      and for developmental problems found later in infancy and childhood. METHODS:
      BAEP studies were performed before discharge in infants treated with
      extracorporeal membrane oxygenation (ECMO), and two specific abnormalities were
      analyzed: elevated threshold and delayed central auditory conduction. Behavioral
      audiometry was repeated during periodic follow-up until reliable responses were
      obtained for all frequencies, and standardized developmental testing was also
      conducted. The sensitivity and specificity of an elevated threshold on the
      neonatal BAEP for detecting subsequent hearing loss, and the relationship of any
      neonatal BAEP abnormality to language or developmental disorders in infancy, were
      calculated. RESULTS: Test results for 46 ECMO-treated infants (57.5%) were
      normal, and those for 34 infants (42.5%) were abnormal, with either elevated wave
      V threshold, prolonged wave I-V interval, or both on neonatal BAEP recordings.
      Most significantly, 7 (58%) of the 12 children with subsequent sensorineural
      hearing loss had left the hospital after showing normal results on threshold
      tests. There was no significant difference in the frequency of hearing loss
      between subjects with abnormal (5/21, or 24%) and those with normal BAEP
      thresholds (7/59, or 12%; Fisher Exact Test, p = 0.28). Therefore the sensitivity
      of neonatal BAEP testing for predicting subsequent hearing loss was only 42%.
      Neonatal BAEP specificity for excluding subsequent hearing loss was 76%. In
      contrast, on language development testing, 19 children demonstrated receptive
      language delay. Of these children, 12 (63%) had abnormal neonatal BAEP recordings
      and 7 (37%) had a normal BAEP threshold, normal central auditory conduction test
      results, or both (p = 0.04). CONCLUSIONS: Neonatal BAEP threshold recordings were
      of limited value for predicting subsequent hearing loss common in ECMO-treated
      survivors. However, an abnormal neonatal BAEP significantly increased the
      probability of finding a receptive language delay during early childhood, even in
      those with subsequently normal audiometry findings. Because neonatal ECMO is
      associated with a high risk of hearing and receptive language disorders, parents
      should be counseled that audiologic and developmental follow-up evaluations in
      surviving children are essential regardless of the results of neonatal BAEP
      testing.

PMID- 9290610
TI  - Brain magnetic resonance imaging in suspected extrapyramidal cerebral palsy:
      observations in distinguishing genetic-metabolic from acquired causes.
AB  - Experienced clinicians recognize that some children who appear to have static
      cerebral palsy (CP) actually have underlying genetic-metabolic disorders. We
      report a series of patients with motor disorders seen in children with
      extrapyramidal CP in whom brain magnetic resonance imaging abnormalities provided
      important diagnostic clues in distinguishing genetic-metabolic disorders from
      other causes. One cause of static extrapyramidal CP, hypoxic-ischemic
      encephalopathy at the end of a term gestation, produces a characteristic pattern
      of hyperintense signal and atrophy in the putamen and thalamus. Other signal
      abnormalities and atrophy in the putamen, globus pallidus, or caudate can point
      to genetic-metabolic diseases, including disorders of mitochondrial and organic
      acid metabolism. Progress in understanding and treating genetic diseases of the
      developing brain makes it essential to diagnose disorders that masquerade as
      static CP. Brain magnetic resonance imaging is a useful diagnostic tool in the
      initial evaluation of children who appear to have CP.

PMID- 9290611
TI  - Dysregulation of calcium homeostasis after severe burn injury in children:
      possible role of magnesium depletion.
AB  - OBJECTIVE: To determine the cause and extent of hypocalcemia observed in children
      after severe burns. DESIGN: We studied 10 children with burns covering 57% +/-
      17% (SD) body surface area, ages 9.6 +/- 4.7 years, who were admitted
      consecutively during a 6-month period. Diet supplied a minimum of 2.7 gm/m2 of
      calcium, 0.3 gm/m2 of magnesium, and 2.2 gm/m2 phosphate. Blood specimens were
      obtained daily for 10 +/- 5 days for the following tests: (1) simultaneous
      analysis for ionized calcium, magnesium, and intact parathyroid hormone (group
      A); (2) two of these children, randomly selected, had serial 2-hour
      determinations on a single day (group B); (3) a modified Ellsworth-Howard test,
      consisting of a 10-minute infusion of synthetic parathyroid hormone 18 +/- 10
      days post-burn and associated changes in urinary cyclic adenosine monophosphate
      excretion and renal threshold phosphate concentration (group C). Three of these
      children, when normomagnesemic, also received a standard magnesium infusion to
      determine magnesium retention (group D). Data were analyzed with chi-square,
      regression analysis, and non-parametric testing as appropriate. RESULTS: All
      patients showed sustained hypocalcemia and hypomagnesemia; intact parathyroid
      hormone response was inappropriately low and response to synthetic parathyroid
      hormone infusion was blunted. Lowest ionized calcium levels were associated with
      hypomagnesemia. CONCLUSION: Hypoparathyroidism and blunted renal response to
      parathyroid hormone suggest that magnesium depletion may contribute to their
      pathogenesis. Magnesium repletion and monitoring are recommended.

PMID- 9290612
TI  - Urinary phosphate/creatinine, calcium/creatinine, and magnesium/creatinine ratios
      in a healthy pediatric population.
AB  - OBJECTIVE: To determine reference values for urinary phosphate/creatinine (Cr)
      concentration ratios and to complete reference values for urinary
      calcium/creatinine and magnesium/creatinine ratios in the second morning urine
      sample of healthy infants, children, and adolescents. DESIGN: Urinary P/Cr,
      Ca/Cr, and Mg/Cr ratios were determined from the second morning urine sample. Two
      urine samples were obtained 1 week apart from most subjects to assess
      reproducibility. SETTING: Kindergartens and schools of Lausanne, Switzerland.
      PARTICIPANTS: A total of 410 healthy children aged 1 month to 17 years (197 girls
      and 213 boys) participated in the study. RESULTS: The 5th and 95th percentiles
      were estimated from 664 urine samples. There were no differences related to sex.
      A nonlinear regression in terms of age was used to smooth the estimated
      percentiles yielding reference curves from which critical values may be obtained
      for any given age. The 95th percentile for urinary Ca/Cr and Mg/Cr agreed with
      previously reported values in children older than 7 years. The upper limit of the
      three solute/creatinine ratios decreased significantly with age: for urinary P/Cr
      from 19.0 mol/mol at 1 month to 2.7 at 14 years; for urinary Ca/Cr from 2.2 to
      0.7 mol/mol, and for urinary Mg/Cr from 2.2 to 0.6 mol/mol. Lower limits varied
      little. Interindividual and intraindividual variations decreased with age.
      CONCLUSIONS: Urinary P/Cr, Ca/Cr, and Mg/Cr ratios vary strongly with age. We
      provide reference values, expressed both in SI and in mass units, for urinary
      P/Cr, Ca/Cr, and Mg/Cr in children aged one month to 17 years.

PMID- 9290613
TI  - Renovascular hypertension in children with moyamoya disease.
AB  - OBJECTIVES: To examine the incidence, clinical and radiologic findings, and
      response to treatment of renovascular hypertension (RVHT) in moyamoya disease
      (MMD). METHODS: A retrospective analysis of medical records in six RVHT cases
      (8.3%) among 72 MMD patients observed from November 1987 to December 1995.
      RESULTS: The age at onset of MMD ranged from 9 months to 7 years 1 month (mean,
      3.3 years). The most common initial manifestation of MMD was transient ischemic
      attack. Hypertension was detected between 4 years 4 months and 12 years 3 months
      (mean, 7.87 years). Unstimulated plasma renin activity was elevated in all six
      cases. Renal ultrasonography and captopril technetium 99m-labeled
      dimercaptosuccinic acid scan showed abnormal findings in four of five and in
      three of four available studies, respectively. However, both imaging studies
      showed abnormal findings only in the most severely affected kidneys even with
      bilateral renal artery stenosis. Renal arteriography revealed bilateral lesions
      in three of the patients and unilateral lesions in the others. Renal angioplasty
      was performed in four cases but was successful in only one and partially
      successful in another. A renal artery specimen obtained during renal
      autotransplantation showed intimal fibroplasia. At the last follow-up, one
      patient had normal blood pressure without the use of antihypertensive agents, but
      the other five patients needed this medication to control blood pressure.
      CONCLUSION: Because RVHT may be more commonly associated with MMD than has
      hitherto been appreciated, it is recommended that blood pressure be carefully
      followed and that diagnostic procedures for RVHT be carried out in hypertensive
      patients with MMD.

PMID- 9290614
TI  - Multilocular thymic cysts in children with human immunodeficiency virus
      infection: clinical and pathologic aspects.
AB  - BACKGROUND: Children with human immunodeficiency virus (HIV) infection have an
      increased susceptibility to severe and unusual infections, malignancies, and
      disorders characterized by abnormal lymphoproliferation (e.g., lymphoid
      interstitial pneumonitis). We report a novel disease entity associated with
      pediatric HIV infection that is characterized by massive enlargement of the
      thymus as a result of lymphoid hyperplasia and multicystic changes. METHODS:
      Eight patients with HIV infection and cystic enlargement of the thymus are
      subject of this report. The status of their HIV disease and its clinical and
      radiologic manifestations at the time of diagnosis of the mediastinal mass are
      described. Tissue specimens were obtained from six patients and examined by
      microscopy and immunohistochemistry. The specimens were also evaluated for the
      evidence of HIV and Epstein-Barr virus by in situ hybridization. RESULTS:
      Patients were between 2.1 and 12.1 years of age, with CD4+ cell counts between
      102 and 733 cells/mm3. In all eight cases an anterior mediastinal mass was
      discovered incidentally on radiography of the chest, and computed tomography of
      the chest revealed a multicystic appearance. Histologic examination demonstrated
      distortion of the thymic architecture by focal cystic changes, lymphoid
      follicular hyperplasia, diffuse plasmacytosis, and multinucleated giant cells. In
      situ hybridization revealed HIV particles on the surface of follicular dendritic
      cells. Further, results of in situ hybridization for EBV were positive in
      lymphoid cells from biopsy samples of four patients. The patients were followed
      between 8 months and 4.8 years. In five patients the mass either decreased in
      size or resolved completely. CONCLUSIONS: We describe a series of children with
      HIV infection and multilocular thymic cysts. We hypothesize that aberrant
      immunoregulation in these HIV-infected children leads to follicular hyperplasia
      and multicystic changes in the thymus, causing massive enlargement. EBV infection
      might also contribute to the pathogenesis of this process. Because none of our
      patients had symptoms from the mass, and there was no evidence of malignancy in
      the examined biopsy samples, it seems prudent to manage such children with
      careful follow-up examinations.

PMID- 9290615
TI  - Treatment of visceral leishmaniasis in children with liposomal amphotericin B.
AB  - We used liposomal amphotericin B as first-choice treatment of visceral
      leishmaniasis in 106 immunocompetent children who acquired the infection in a
      temperate region of southern Europe (Italy) where Leishmania infantum visceral
      leishmaniasis is endemic. The aim of the study was to identify the minimum total
      dose of liposomal amphotericin B needed to cure the infection in children and
      reduce the period of hospitalization. We conclude that the optimal regimen in
      immunocompetent children with L. infantum visceral leishmaniasis to be a total
      dose of 18 mg/kg of liposomal amphotericin B (3 mg/kg per day for 5 days,
      followed by 3 mg/kg administered as an outpatient regimen on day 10).

PMID- 9290616
TI  - Airway hyperreactivity in children with sickle cell disease.
AB  - Progressive restrictive defect with increasing age, obstructive lung disease, and
      bronchodilator responsiveness have been reported in sickle cell disease (SCD).
      Because airway hyperreactivity (AHR) can be underestimated when assessed by
      bronchodilator responsiveness in patients with normal baseline lung function, the
      aim of this study was to investigate the prevalence of AHR in SCD by cold-air
      bronchial provocation testing, and to assess whether AHR can be present in
      symptom-free patients with SCD. Forty patients aged 6 to 19 years (mean, 10.7
      years +/- 3.5 SD) performed pulmonary function tests. Eighteen were known to have
      a history of reactive airway disease (RAD group), and 22 had no known history of
      RAD (non-RAD group). A control group, aged 6 to 7 years (mean, 10.5 +/- 3.1
      years), consisted of 10 siblings of the non-RAD SCD group. There were no
      significant differences in age and height among the groups. If the forced
      expiratory volume in 1 second (FEV1) was greater than 70%, cold air challenge
      (CACh) was performed; if the FEV1 was less than 70%, aerosolized bronchodilator
      therapy was given. A decrease in FEV1 of more than 10% after CACh or an increase
      in FEV1 of 12% or greater after bronchodilator inhalation was considered evidence
      of AHR. In the RAD group, the total lung capacity was 88.9% +/- 14.0% of race
      corrected predicted values, the forced vital capacity was 91.2% +/- 12.6%, and
      FEV1 was 85.3% +/- 16.2%. The mean maximal percent fall in FEV1 after CACh (n =
      13) was 18.5% +/- 9.6% and was greater than 10% in 11 of 13 patients. The mean
      increase in FEV1 after bronchodilator therapy (n = 5) was 11.5% +/- 8.3%, and it
      was greater than 12% in 4 of 5 patients. In the non-RAD group the baseline total
      lung capacity was 101.6% +/- 11.7%, forced vital capacity was 95.5% +/- 10.2%,
      and FEV1 was 93.3% +/- 13.2%. The mean maximal percent fall in FEV1 after CACh (n
      = 19) was 14.1% +/- 8.8% and was greater than 10% in 13 of 19 patients. The mean
      increase in FEV1 after bronchodilator therapy (n = 3) was 14.7% +/- 11.3%, and
      was 12% of greater in 1 of 3 patients. In the control group the baseline total
      lung capacity was 105.7% +/- 12.1%, forced vital capacity was 96.2% +/- 11.1%,
      and FEV1 was 92.9% +/- 10.3%. The mean maximal percent fall in FEV1 was 5.0% +/-
      2.5%, and was greater than 10% in none of 10 patients. The prevalence of AHR in
      the control group, the RAD group, and the non-RAD group was zero, 83%, and 64%,
      respectively (p < 0.0001). The overall prevalence in the SCD group was 73%. We
      conclude that there is a high prevalence of AHR in children with SCD and that
      airway hyperreactivity may exist in patients with SCD even in the absence of the
      clinical symptoms of RAD. AHR may be a significant component of sickle cell lung
      disease.

PMID- 9290617
TI  - Glucose-6-phosphate dehydrogenase Durham: a de novo mutation associated with
      chronic hemolytic anemia.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked enzyme
      defect. We report a new variant, G6PD Durham713G, that is associated with chronic
      nonspherocytic hemolytic anemia. The G6PD Durham713G variant has a unique
      biochemical and enzymatic profile and a novel A-->G substitution mutation at
      nucleotide 713, changing lysine to arginine at amino acid 238. This mutation was
      not found in the mother of our patient, indicating that G6PD Durham713G resulted
      from a de novo mutation.

PMID- 9290618
TI  - Relationship between physical inactivity and adiposity in prepubertal boys.
AB  - OBJECTIVE: To study the relationship between the energy expenditure for activity
      (EEAct), the level of activity and adiposity in a group of 9-year-old boys (n =
      28) with different body composition (body weight, 38 +/- 10 kg [range, 23 to 66
      kg]; fat mass, 23% +/- 10% [range, 8% to 42%]). METHODS: Total energy expenditure
      (TEE) was measured by means of the heart-rate monitoring method. EEAct was
      calculated as TEE-(REE+0.1 TEE), where REE is the postabsorptive resting energy
      expenditure and 0.1 TEE corresponds to the postprandial thermogenesis
      (approximately 10% of TEE). RESULTS: TEE, REE, and EEAct were 9388 +/- 1859, 5154
      +/- 642, and 3295 +/- 1356 l J/day, respectively. Daily time devoted to sedentary
      and nonsedentary activities averaged 290 +/- 155 minutes (range, 69 to 621) and
      534 +/- 150 minutes (range, 180 to 783), respectively. Time spent on sedentary
      activities was directly proportional to fat mass percentage (r = 0.46; p < 0.05).
      It was the only variable, among the free-living physical-activity [EEAct,
      TEE/(REE+0.1 TEE) ratio, time spent in nonsedentary and sedentary activities]
      variables, which remained significantly in the multiple step-down regression
      analysis final equation (r = 0.46; p < 0.05). CONCLUSIONS: The positive
      relationship between adiposity and time spent on sedentary activities in 9-year
      old boys suggests the importance of the role played by muscular activity, at
      least in the maintenance of obesity in childhood. Prepubertal children should be
      encouraged to spend less time on sedentary activities to treat and prevent their
      obesity.

PMID- 9290619
TI  - Elevated IgG titer against the C region of streptococcal M protein and its
      immunodeterminants in patients with poststreptococcal acute glomerulonephritis.
AB  - OBJECTIVE: To determine the immune responses to the streptococcal M protein in
      patients with poststreptococcal acute glomerulonephritis (PSAGN). STUDY DESIGN:
      The gene coding type 12 M protein of group A streptococcus (M12), a known PSAGN
      associated serotype, was cloned and expressed in Escherichia coli to investigate
      the specific immune responses to the M12 protein in patients with PSAGN.
      Recombinant M proteins for the variable N-terminal half (AB region) and conserved
      C-terminal half (C region) were produced separately. IgG titers against each
      region were measured by enzyme-linked immunosorbent assay in patients with PSAGN
      (n = 51), uncomplicated streptococcal pharyngitis (n = 26), chronic
      glomerulonephritis (n = 10), and in healthy control subjects (n = 51).
      Immunodominant domains within the M protein in PSAGN were further investigated by
      use of overlapping synthetic peptides. RESULTS: IgG titers against the C region,
      but not the AB region, were markedly higher in the PSAGN group than in other
      groups (p < 0.01), and these titers were maintained for at least several months
      after antistreptolysin O or antistreptokinase levels had returned to normal.
      Studies with overlapping synthetic peptides demonstrated that increased IgG
      reactivity was observed against the C repeat blocks. CONCLUSION: IgG titers
      against the C region are significantly elevated in patients with PSAGN, and it
      may be a diagnostic marker for PSAGN.

PMID- 9290620
TI  - Spontaneous remission of congenital leukemia.
AB  - Most patients with congenital leukemia do not survive past infancy despite
      aggressive chemotherapy. We describe three patients with congenital leukemia who
      have undergone prolonged periods of spontaneous remission. Our experience
      suggests that some patients with congenital leukemia may benefit from initial
      conservative management without chemotherapy. We summarize the clinical
      presentations of these patients and review the literature.

PMID- 9290621
TI  - Sudden neonatal death in carnitine transporter deficiency.
AB  - A newborn infant died suddenly and unexpectedly on day 5 of life. Postmortem
      investigations led to a suspicion of carnitine transporter deficiency, a
      diagnosis supported by the finding that both parents are heterozygotes for this
      disorder. The fasting stress caused by poor breast-feeding with no formula
      supplements and, possibly, the vegetarian diet of the mother were likely the
      critical factors leading to neonatal death, an outcome previously not described
      in this disorder.

PMID- 9290622
TI  - Celiac disease and selective immunoglobulin A deficiency.
AB  - Selective IgA deficiency was observed in 12 of 688 (1.7%) patients with celiac
      disease who were clinically undistinguishable from patients with celiac disease
      with normal IgA levels. This high prevalence of IgA deficiency in patients with
      celiac disease makes serum IgA assay advisable when screening for celiac disease
      is performed by measurement of antigliadin antibodies or anti-IgA endomysium
      antibodies. Similarly, subjects with IgA deficiency should be considered at risk
      of celiac disease.

PMID- 9290623
TI  - Posttransplantation lymphoproliferative disorders in pediatric thoracic organ
      recipients.
AB  - OBJECTIVE: To determine the frequency, predisposing factors, clinical
      presentation, and outcome of posttransplantation lymphoproliferative disorders
      (PTLDs) in pediatric thoracic organ transplant recipients. METHODS: Retrospective
      review of the medical records of all 120 children who survived longer than 1
      month after thoracic organ transplantation at our center. RESULTS: PTLD was
      diagnosed in 14 patients (11.7%), including 7.7% of heart and 19.5% of heart
      lung/lung recipients. Presentation of PTLD was variable, ranging from
      asymptomatic lung nodules on chest radiograph to diffuse multiorgan failure.
      Treatment with a reduction of immunosuppression and antiviral therapy resulted in
      resolution of PTLD in eight patients. Eight patients died. PTLD contributed to
      death in five. No patient seropositive for Epstein-Barr virus (EBV) before
      transplantation had PTLD. There was a significant association between primary EBV
      infection after transplantation and the presence of PTLD. CONCLUSIONS: PTLD
      occurs with greater frequency in pediatric thoracic organ transplant recipients
      than in the adult transplant population. Primary EBV infection after
      transplantation is the major risk factor for the development of PTLD. Patients in
      whom primary EBV infection develops after transplantation should be managed with
      a reduction in immunosuppression and with heightened surveillance for the
      development of PTLD.

PMID- 9290625
TI  - Clostridium septicum infection in children with cyclic neutropenia.
AB  - Atraumatic Clostridium septicum infection is rare in infancy and childhood and is
      associated with a high mortality rate. Although in adults it has been reported to
      occur mainly in patients with gastrointestinal malignancy, pediatric cases were
      always associated with neutropenia. About 70% of the cases were described in
      children with neutropenia caused by chemotherapy and 30% were found in children
      with cyclic neutropenia. No case was described in children with other forms of
      congenital severe neutropenia. We describe three children with cyclic neutropenia
      and severe Clostridium septicum infection, discuss the various possibilities of
      causation, and the need for prompt and aggressive treatment of this serious
      condition.

PMID- 9290624
TI  - Low prevalence of antibody to hepatitis C virus in an urban adolescent
      population.
AB  - We tested 869 subjects attending either an urban adolescent medicine clinic or a
      school-based clinic for antibody to hepatitis C virus. Demographic data indicated
      a representative study sample, and behaviors associated with hepatitis C virus
      transmission. One subject (0.1%) was seropositive for antibody to hepatitis C
      virus, indicating a very low prevalence of hepatitis C virus exposure in
      adolescents.

PMID- 9290626
TI  - Neurodevelopmental dysfunction among nonreferred children with idiopathic
      megalencephaly.
AB  - PURPOSE: To determine whether nonreferred children with idiopathic megalencephaly
      show evidence of specific neurodevelopmental dysfunction compared with sibling
      control subjects and age-matched control subjects. DESIGN: Cross-sectional, case
      control study in a large, suburban pediatric practice. Subjects included 20
      children between the ages of 6 and 15 years with a head circumference at greater
      than the 98th percentile, 19 siblings of these children with normalsize heads,
      and 16 age-matched control subjects. Standardized tests of language, academic
      achievement, visuomotor integration, motor function, and neurodevelopmental
      function were administered. RESULTS: Multivariate analysis, with control for age,
      showed a main effect for the presence of megalencephaly (F = 3.2; p < 0.05).
      Follow-up univariate analyses, with control for age, showed that children with
      megalencephaly had poorer performance on tasks of upper limb speed, visuomotor
      control, running speed, bilateral coordination, visuomotor integration, naming
      fluency, and minor neurologic indicators. CONCLUSION: The relationship between
      idiopathic megalencephaly and external hydrocephalus in infants is discussed.
      Results show that so-called "benign" idiopathic megalencephaly in nonreferred
      school-age children appears to be a clinical entity associated with subtle motor
      problems and neurodevelopmental dysfunction.

PMID- 9290627
TI  - Centers for disease control and prevention lead guidelines: do pediatricians know
      them?
AB  - American Academy of Pediatrics (AAP) fellows responded to a questionnaire
      measuring knowledge of 1991 Centers for Disease Control and Prevention (CDC)
      guidelines. Generalists' scores on a knowledge scale were positively correlated
      with reporting CDC and AAP documents as knowledge sources, and negatively
      correlated with private practice, medical school as a knowledge source, and age.
      However, private practitioners who read AAP documents scored well.

PMID- 9290628
TI  - Newborn screening for 21-hydroxylase deficiency: results of CYP21 molecular
      genetic analysis.
AB  - Blood samples for plasma steroid hormone determinations and molecular genotype
      analysis of the 21-hydroxylase gene (CYP21) were obtained from 15 infants
      identified through a voluntary newborn screening program. Mutations were
      identified on both CYP21 alleles in 12 (80%) of 15 infants; all had confirmatory
      plasma 17-hydroxyprogesterone concentrations > 3500 ng/dl. No patient was found
      to carry mutations associated with late-onset 21-hydroxylase deficiency. Newborn
      screening hastened diagnosis in eight infants.

PMID- 9290629
TI  - Ibuprofen and/or acetaminophen: what price for "euthermia"?

PMID- 9290630
TI  - Ibuprofen and/or acetaminophen: what price for "euthermia"?

PMID- 9290632
TI  - From managed competition to managed cooperation: theory and lessons from the
      British experience.
AB  - The United Kingdom led the world in transforming the largest single health care
      system from a publicly administered service to a set of interlocking contracts.
      Policy lessons that can be adapted by employers, nations, and other large payers
      are identified. These lessons are drawn from the improvements that the British
      made over the design of managed competition, the mistakes and problems they
      experienced, the underlying trends toward privatization and class discrimination,
      and the limitations to competition that have led the British toward managed
      cooperation in collaborative purchasing for the health needs of communities. Yet
      market reform and the rhetoric of efficiency have justified the shrinking of
      health services, the shift of costs to household budgets, and the use of public
      moneys to support private services and investors at greater expense by moving
      properties and services off the public ledger. In these ways, managed competition
      can Americanize health care and pose fundamental questions about what policy
      goals are really being pursued.

PMID- 9290631
TI  - HELIOX in children with acute severe asthma.

PMID- 9290633
TI  - Physician responses to global physician expenditure budgets in Canada: a common
      property perspective.
AB  - Global expenditure budgets in the fee-for-service physician sector create
      management problems for both funders and physicians. Global expenditure cap
      policies must be designed, and appropriate institutional structures created, to
      mitigate perverse utilization incentives, manage collective utilization, and
      diffuse the internal professional and the funder-profession tensions created by a
      capped budget. Two Canadian provinces that adopted different approaches to the
      design of their physician expenditure cap policies experienced different outcomes
      in utilization growth. The outcomes, however, are the opposite to what one would
      predict based on an analysis of the incentive structures embodied in the two
      provinces' policies. An analytic framework developed for the study of common
      property resources is applied to the differing physician responses to global
      budgets across the two provinces. The insights offered by this framework can
      guide policy design for global physician budgets, and they indicate the critical
      importance of physician acceptance of such a policy.

PMID- 9290634
TI  - Medical necessity in Canadian health policy: four meanings and ... a funeral?
AB  - Four meanings of medical necessity have emerged, evolved, and dominated past and
      current health policy debates about the appropriate level of service coverage
      under Canada's health insurance program. To explore the shift in definition,
      provincial government and national health care association position papers
      responding to federal legislative and policy reviews of Canada's health insurance
      program from 1957 to 1984 were examined, as were more current reports on medical
      necessity. Four meanings of medical necessity predominated: "what doctors and
      hospitals do"; "the maximum we can afford"; "what is scientifically justified";
      and "what is consistently funded across all provinces." These meanings changed
      with time as different stakeholder associations and governments redefined the
      concept of medical necessity to achieve different policy objectives for health
      service coverage under Canada's health insurance program.

PMID- 9290635
TI  - Informing consumer decisions in health care: implications from decision-making
      research.
AB  - Despite the wider dissemination of health plan report cards, little is known
      about whether consumers will use this information in making plan and provider
      choices. Studies of human judgment and decision making are reviewed, as are their
      implications for devising strategies to inform consumers. The limitations of
      human information processing suggest that many consumers will not use performance
      information in making choices. Strategies are needed to support consumers who
      prefer to rely on intermediaries as well as those who wish to apply the
      information for their own use. Many current strategies are based on assumptions
      not supported by existing decision-making research. Although there is much to
      learn about assisting consumers in making informed choices, a great deal is known
      from decision-making research. Our approaches and our research agenda must be
      based on this existing foundation of knowledge.

PMID- 9290636
TI  - Cloning and characterization of elongation specific endo-1,4-beta-glucanase
      (cel1) from Arabidopsis thaliana.
AB  - The isolation of an elongation-specific endo-1,4-beta-glucanase-cel1 from
      Arabidopsis thaliana was made possible by the fact that considerable homology
      exists between different endo-1,4-beta-glucanase (EGase) genes from different
      plants. Degenerate primers were synthesized based on two conserved regions from
      the avocado and tomato cellulase amino acid sequences. The A.thaliana cel1 cDNA
      gene was found to encode a 54kDa protein; sequence comparison with the avocado
      EGase revealed 56% identity. Northern blot analysis of cel1 suggested its
      developmental regulation. RNA transcripts were undetectable in fully expanded
      leaves as well as at the basal internode of flowering stems. However, a strong
      transcript signal was detected in the elongating zone of flowering stems of
      normal plants. The RNA transcript level of cel1 in the elongating zone of dwarf
      flowering stems was significantly lower than in the corresponding zone in normal
      plants. This suggests cel1's involvement in cell elongation in A. thaliana.
      Transgenic tobacco plants transformed with the putative cel1 promoter region
      fused to the gus reporter gene, showed a significant GUS staining both in shoot
      and root elongating zones. These results further substantiate the link between
      cel1 expression and plant cell elongation.

PMID- 9290637
TI  - Maize glutathione-dependent formaldehyde dehydrogenase cDNA: a novel plant gene
      of detoxification.
AB  - We have previously shown that intact plants and cultured plant cells can
      metabolize and detoxify formaldehyde through the action of a glutathione
      dependent formaldehyde dehydrogenase (FDH), followed by C-1 metabolism of the
      initial metabolite (formic acid). The cloning and heterologous expression of a
      cDNA for the glutathione-dependent formaldehyde dehydrogenase from Zea mays L. is
      now described. The functional expression of the maize cDNA in Escherichia coli
      proved that the cloned enzyme catalyses the NAD(+)- and glutathione (GSH)
      dependent oxidation of formaldehyde. The deduced amino acid sequence of 41 kDa
      was on average 65% identical with class III alcohol dehydrogenase from animals
      and less than 60% identical with conventional plant alcohol dehydrogenases (ADH)
      utilizing ethanol. Genomic analysis suggested the existence of a single gene for
      this cDNA. Phylogenetic analysis supports the convergent evolution of ethanol
      consuming ADHs in animals and plants from formaldehyde-detoxifying ancestors. The
      high structural conservation of present-day glutathione-dependent FDH in
      microorganisms, plants and animals is consistent with a universal importance of
      these detoxifying enzymes.

PMID- 9290638
TI  - Effect of pollination on accumulation of ACC synthase and ACC oxidase
      transcripts, ethylene production and flower petal abscission in geranium
      (Pelargonium x hortorum L.H. Bailey).
AB  - Self-pollination of diploid zonal geranium (Pelargonium x hortorum L.H. Bailey)
      florets leads to a dramatic rise in ethylene production, followed by abscission
      within 4 h. Neither wounding of the stigma, pollination with tetraploid pollen,
      nor heat-killed self pollen could elicit as much ethylene production and petal
      abscission as self-pollination. A cDNA sharing sequence identity with ACC
      synthase (GACS2) and three different cDNAs sharing sequence identity with ACC
      oxidase (GACO1, GACO2, GACO3) were isolated from geranium pistils. Transcripts
      hybridizing with these probes increased slightly in response to self-pollination,
      but the degree of accumulation in response to various treatments did not
      correlate with ethylene production. When calculated on a per-plant-part basis,
      transcripts hybridizing with GACS2 were equally distributed among the
      stigma+style, sterile ovary, and ovary tissues, but transcripts hybridizing with
      the three ACC oxidase clones were differentially distributed. All transcripts
      were differentially expressed among the other tissues of the plant, with GACO1
      being the most widely distributed. Ethylene production in geranium pistils was
      not autocatalytic. Propylene failed to induce ethylene production and ethylene
      did not induce the accumulation of ACC synthase or ACC oxidase transcripts. ACC
      accumulated in the stigma and style, and to a smaller extent in the sterile
      ovary, after pollination. These data support a model of pollination-induced
      ethylene production by post-transcriptional regulation of ethylene biosynthetic
      gene expression.

PMID- 9290639
TI  - Cloning, molecular characterization and expression pattern of a strawberry
      ripening-specific cDNA with sequence homology to pectate lyase from higher
      plants.
AB  - A strawberry fruit cDNA showing sequence similarity to higher-plant pectate lyase
      genes has been isolated by differential screening of a strawberry fruit cDNA
      subtractive library. The cDNA contains a 396 amino acids open reading frame
      corresponding to a 44.8 kDa protein. The transcript is predominantly expressed in
      ripe fruits and was not detected at high levels in any other plant tissues. The
      removal of the achenes from unripe green fruits induced the expression of this
      putative pectate lyase gene. In common with other ripening related genes in
      strawberry, this induction was partially inhibited by treatment of de-achened
      fruit with the auxin NAA. Southern blot analysis of genomic DNA indicates that in
      strawberry there is more than one putative pectate lyase gene. We propose that
      the ripe fruit expression of this strawberry gene with similarity to pectate
      lyases could be related to cell wall pectin degradation contributing to
      strawberry fruit softening.

PMID- 9290641
TI  - Characterization of Zea mays endosperm C-24 sterol methyltransferase: one of two
      types of sterol methyltransferase in higher plants.
AB  - We report the characterization of a higher-plant C-24 sterol methyltransferase by
      yeast complementation. A Zea mays endosperm expressed sequence tag (EST) was
      identified which, upon complete sequencing, showed 46% identity to the yeast C-24
      methyltransferase gene (ERG6) and 75% and 37% amino acid identity to recently
      isolated higher-plant sterol methyltransferases from soybean and Arabidopsis,
      respectively. When placed under GALA regulation, the Z. mays cDNA functionally
      complemented the erg6 mutation, restoring ergosterol production and conferring
      resistance to cycloheximide. Complementation was both plasmid-dependent and
      galactose-inducible. The Z. mays cDNA clone contains an open reading frame
      encoding a 40 kDa protein containing motifs common to a large number of S
      adenosyl-L-methionine methyltransferases (SMTs). Sequence comparisons and
      functional studies of the maize, soybean and Arabidopsis cDNAs indicates two
      types of C-24 SMTs exist in higher plants.

PMID- 9290640
TI  - ACGT and vicilin core sequences in a promoter domain required for seed-specific
      expression of a 2S storage protein gene are recognized by the opaque-2 regulatory
      protein.
AB  - The expression of Brazil nut storage albumin genes is highly regulated during
      seed development. Several sequences in the promoter of one of these genes show
      homologies with the target sites of the maize O2 bZIP regulatory protein. We
      therefore asked whether the O2 protein would recognize these promoter sequences.
      We show that the O2 protein binds to three different sequences (F1, F2 and F3).
      F1 and F3 are hybrid C/G and A/G boxes, respectively, that are homologous to the
      O2-binding site of a maize alpha-zein gene. F2 is a new O2-binding sequence
      related to the O2 target sites of the Coix alpha-coxin, the maize b-32 genes and
      the AP-1 pseudopalindrome. Molecular modelling showed that an Asn and a Ser in
      the 02 DNA binding domain make different base-specific contacts with each
      operator. 5' Promoter deletions of the be2S1 gene showed that the domain
      containing the O2 target sites F1 and F2 is required for detectable reporter gene
      expression in transgenic tobacco seeds. Moreover, the homologous coix O2 protein
      was shown to in situ transactivate the promoter region encompassing the three O2
      binding sites F1, F2 and F3. Thus, these sites may be in vivo regulatory
      sequences mediating activation by bZIP regulatory proteins.

PMID- 9290642
TI  - Cloning and characterization of the calreticulin gene from Ricinus communis L.
AB  - A full-length cDNA encoding a calreticulin-like protein was isolated by immune
      screening a germinating castor bean endosperm cDNA library with antisera raised
      to the total lumenal fraction of purified plant endoplasmic reticulum. The
      calcium-binding properties of the recombinant protein were characterized and
      shown to be essentially identical to those reported for the mammalian
      calreticulin. Calcium overlays and immune blot analysis confirmed the endoplasmic
      lumenal identity of this reticuloplasmin. Probing protein blots of endoplasmic
      reticulum subfractions with radio-iodinated calreticulin showed specific
      associations with various polypeptides including one identified as the abundant
      reticuloplasmin protein disulfide isomerase. Characterization of the
      corresponding genomic clones revealed that calreticulin is encoded by a single
      gene of 3 kb in castor. The full genomic sequence reveals the presence of 12
      introns, 12 translated exons, and one exon containing the last three amino acids
      of the translated sequence and the 3'-untranslated region of the gene. Northern
      blot analysis of RNA isolated from various organ tissues showed a basal
      constitutive level of expression throughout the plant, but more abundant mRNA
      being detected in tissues active in secretion. This was confirmed by analysis of
      transgenic tobacco plants containing 1.8 kb of 5'-untranslated genomic sequence
      fused to the beta-glucuronidase reporter gene (GUS) showed a more localized
      pattern of expression. Activity being localized to the vasculature (phloem, root
      hairs and root tip) in vegetative tissue, and being strongly expressed in the
      floral organs including the developing and germinating seed.

PMID- 9290643
TI  - Frequent collinear long transfer of DNA inclusive of the whole binary vector
      during Agrobacterium-mediated transformation.
AB  - When Agrobacterium was used to transform Nicotiana plumbaginifolia protoplasts
      and Arabidopsis thaliana roots and seedlings, a large number of plants were found
      in which not only the T-region defined by the border repeat sequences but the
      entire binary vector was integrated, as determined by both PCR and Southern
      analysis techniques. N. plumbaginifolia protoplast co-cultivation experiments
      yielded 3 out of 5 transformants with collinear sequence past the left border. In
      Arabidopsis root transformation experiments, 33% (6/18) of the transformants had
      T-DNA which exceeded the left border repeat. Vacuum infiltration of Arabidopsis
      seedlings produced even a greater percentage of transformants with sequences
      outside the left border repeat (62%, 39/63). The long transfer DNA cosegregated
      with the T-region encoded hygromycin resistance in the T2 progeny eliminating the
      possibility that long transfer DNA was of extrachromosomal or Agrobacterium
      origin. The high frequency of long transfer after vacuum infiltration of A.
      thaliana needs to be considered when analyzing T-DNA tagged mutants.

PMID- 9290644
TI  - Differential and wound-inducible expression of 1-aminocylopropane-1-carboxylate
      oxidase genes in sunflower seedlings.
AB  - In an effort towards understanding the biochemical properties and physiological
      functions of 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase homologues, we
      have isolated three ACC oxidase clones from sunflower (Helianthus annuus)
      seedlings. ACCO1 is a cDNA clone while ACCO2 and ACCO3 and reverse transcriptase
      polymerase chain reaction clones. Southern analysis indicated the existence of at
      least three members in the sunflower ACC oxidase gene family. Expression studies
      showed that ACCO3 was equally expressed in leaves, hypocotyl, and roots of
      sunflower seedlings, but it constituted only a small amount of the total ACC
      oxidase transcripts. In contrast, ACCO1 and ACCO2 were differentially expressed
      in these organs. ACCO1 mRNA was most abundant in roots, whereas ACCO2 was the
      major homologue in leaves and in hypocotyl. The levels of total ACC oxidase
      transcripts in these organs were also determined. High ACC oxidase transcript
      levels were associated with tissue containing rapidly dividing cells. Wounding
      and silver ion treatments of hypocotyls increased ACC oxidase mRNA levels and ACC
      oxidase activity; these events being consistent with the increases in ethylene
      production. In contrast, ACC oxidase protein levels were not affected by these
      treatments, suggesting that either a translational regulation and/or a rapid turn
      over of the protein is involved in both wound- and silver ion-induced gene
      expression. Contrary to data in the literature, we found that auxins, ethephon
      and ACC did not affect ACC oxidase mRNA levels in sunflower hypocotyls. The
      complexity of ACC oxidase regulation and the significance of organ differential
      expression of ACC oxidase genes are discussed.

PMID- 9290646
TI  - Cloning and expression of a PR5-like protein from Arabidopsis: inhibition of
      fungal growth by bacterially expressed protein.
AB  - Pathogenesis-related (PR)-5 proteins are a family of proteins that are induced by
      different phytopathogens in many plants and share significant sequence similarity
      with thaumatin. We isolated a complementary DNA (ATLP-3) encoding a PR5-like
      protein from Arabidopsis which is distinct from two other previously reported PR5
      cDNAs from the same plant species. The predicted ATLP-3 protein with its amino
      terminal signal sequence is 245 amino acids in length and is acidic with a pl of
      4.8. The deduced amino acid sequence of ATLP-3 shows significant sequence
      similarity with PR5 and thaumatin-like proteins from Arabidopsis and other plants
      and contains a putative signal sequence at the amino-terminus. The expression of
      ATLP-3 and a related gene (ATLP-1) that we previously isolated from Arabidopsis
      was induced by pathogen infection and salicylic acid, a known inducer of
      pathogenesis-related genes. Southern blot analysis indicates that the ATLP-1 and
      ATLP-3 are coded by single-copy genes. To study the effect of ATLP-1 and ATLP-3
      proteins on fungal growth, the cDNA regions corresponding to putative mature
      protein were expressed in Escherichia coli and the cDNA encoded proteins were
      purified. ATLP-1 and ATLP-3 proteins cross-reacted with anti-osmotin and anti
      zeamatin antibodies. ATLP-3 protein showed antifungal activity against several
      fungal pathogens suggesting that ATLP-3 may be involved in plant defense against
      fungal pathogens.

PMID- 9290647
TI  - A promoter directing epidermal expression in transgenic alfalfa.
AB  - We describe the isolation, cloning and expression of a 2.8 kb promoter fragment
      of the Blec4 gene from pea (Pisum sativum cv. Alaska) and demonstrate that it is
      capable of directing the expression of the beta-glucuronidase coding region to
      the developing epidermal tissue of vegetative and floral shoot apices of
      transgenic alfalfa (Medicago sativa cv. RegenSY). The Blec4 promoter represents a
      useful tool with which to target the expression of foreign genes to the epidermal
      layer of actively growing shoots. The activity of the Blec4 promoter in the
      epidermis of the shoot apex makes it particularly suitable for genetically
      engineering defense against insects and diseases that attack the growing shoot
      apex.

PMID- 9290645
TI  - Molecular cloning and characterization of desacetoxyvindoline-4-hydroxylase, a 2
      oxoglutarate dependent-dioxygenase involved in the biosynthesis of vindoline in
      Catharanthus roseus (L.) G. Don.
AB  - A 2-oxoglutarate-dependent dioxygenase (EC 1.14.11.11) which catalyzes the 4
      hydroxylation of desacetoxyvindoline was purified to homogeneity. Three
      oligopeptides isolated from a tryptic digest of the purified protein were
      microsequenced and one oligopeptide showed significant homology to hyoscyamine 6
      beta-hydroxylase from Hyoscyamus niger. A 36-mer degenerate oligonucleotide based
      on this peptide sequence was used to screen a Catharanthus roseus cDNA library
      and three clones, cD4H-1 to -3, were isolated. Although none of the three clones
      were full-length, the open reading frame on each clone encoded a putative protein
      containing the sequence of all three peptides. Primer extension analysis
      suggested that cD4H-3, the longest cDNA clone, was missing 156 bp at the 5' end
      of the clone and sequencing of the genomic clone, gD4H-8, confirmed these
      results. Southern blot analysis suggested that d4h is present as a single-copy
      gene in C. roseus which is a diploid plant, and the significant differences in
      the sequence of the 3'-UTR between cD4H-1 and -3 suggest that they represent
      dimorphic alleles of the same hydroxylase. The identity of the clone was further
      confirmed when extracts of transformed Escherichia coli expressed D4H enzyme
      activity. The D4H clone encoded a putative protein of 401 amino acids with a
      calculated molecular mass of 45.5 kDa and the amino acid sequence showed a high
      degree of similarity with those of a growing family of 2-oxoglutarate-dependent
      dioxygenases of plant and fungal origin. The similarity was not restricted to the
      dioxygenase protein sequences but was also extended to the gene structure and
      organization since the 205 and 1720 bp introns of d4h were inserted around the
      same highly conserved amino acid consensus sequences as those for e8 protein,
      hyoscyamine-6 beta-hydroxylase and ethylene-forming enzyme. These results provide
      further support that a common ancestral gene is responsible for the appearance of
      this family of dioxygenases. Hydroxylase assays and RNA blot hybridization
      studies showed that enzyme activity followed closely the levels of d4h
      transcripts, occurring predominantly in young leaves and in much lower levels in
      stems and fruits. In contrast, etiolated seedlings which contained considerable
      levels of d4h transcripts had almost undetectable hydroxylase activity, whereas
      exposure of seedlings to light resulted in a rapid increase of enzyme activity
      without a significant further increase in d4h transcripts over those detected in
      dark-grown seedlings. These results suggest that the activating effect of light
      may occur at a point downstream of transcription which remains to be elucidated.

PMID- 9290649
TI  - Le Fort III advancement with gradual distraction using internal devices.
AB  - The purpose of this report is to demonstrate a practical clinical method for
      advancement of the midface using a combination of Le Fort III osteotomy and
      gradual distraction. Use of internal, submergible distraction devices and
      modification of the Ilizarov distraction protocol are presented. Case reports
      show the effect of departing from the Ilizarov protocol by eliminating the
      latency period, initiating distraction intraoperatively, and rapidly distracting
      the segments postoperatively. A method of controlling fragment distraction rate
      by regulating pressures within the osteotomy site is described. The design and
      surgical application of internal distraction devices are shown. Nine patients
      with midface hypoplasia related to craniofacial anomalies underwent Le Fort III
      osteotomies assisted by gradual distraction. Ages ranged from 4 to 13 years.
      Custom internal distraction devices were employed to meet the unique requirements
      of each patient. Activation of the distraction device was accomplished by a
      percutaneous pin that remained in place for 3 to 5 days. The rate of transport
      was determined by regulating the forces within the distraction site. The internal
      devices remained in place for 6 months for fixation of the transported fragment.
      Midface advancement, measured as the anterior displacement of the infraorbital
      rim, ranged from 16 to 30 mm, with a mean of 20 mm. The typical force required to
      produce incremental movement of the Le Fort III osteotomy was found to be between
      7 and 9 kg as transport exceeded 10 mm. Four patients with obstructive sleep
      apnea prior to surgery had resolution of the disorder. All the midface
      advancements remained clinically stable. Establishment of osseous continuity was
      verified by surgical examination in the four patients in whom the distraction
      devices have been removed. Combining intraoperative advancement of the Le Fort
      III osteotomy with gradual distraction consistently resulted in larger movements
      than could be achieved with conventional osteotomies and rigid fixation alone.
      The pediatric craniofacial skeleton responds differently to distraction than does
      the orthopedic skeleton. Eliminating the latency period, establishing a
      substantial bone gap intraoperatively, and rapidly distracting the fragment
      postoperatively did not adversely affect the osseous union in these patients. The
      internal, submergible feature of the device design offers advantages in patient
      acceptance, fixation stability, and wound management. This method of Le Fort III
      midface advancement has been shown to be clinically practical and effective.

PMID- 9290650
TI  - A fresh cadaveric study of the paratubal muscles: implications for eustachian
      tube function in cleft palate.
AB  - The aims of this anatomic investigation were to examine the levator veli
      palatini, tensor veli palatini, and salpingopharyngeus muscles in relation to
      normal eustachian tube function and to analyze the clinical implications of these
      data for tubal physiology in cleft palate individuals. Detailed dissections under
      3.2x loupe magnification were conducted on the paratubal muscles of 15 fresh
      human adult cadaveric head specimens, paying particular attention to their
      cranial base anatomy. Each half of the cadaveric heads was examined separately,
      giving a sample size of 30. The cranial base origin of the levator veli palatini
      was the junction of the cartilaginous and bony parts of the eustachian tube.
      Contrary to statements in the existing literature, it had no origin from the
      quadrate area of the petrous temporal bone. In its path toward the velum, it was
      related inferiorly and lay almost parallel to the tube. The tensor veli palatini
      originated from the scaphoid fossa of the sphenoid bone and the tube. In contrast
      to previous descriptions, it was found to consist of a single sheet of muscle
      with no bilaminar structure. Its axis was oblique to that of the tube. The
      salpingopharyngeus was a slender muscle attached to the posteroinferior aspect of
      the pharyngeal end of the tube. It inserted into the palatopharyngeus inferiorly.
      These morphologic characteristics and anatomic relationships suggest that (1) the
      levator veli palatini opens the eustachian tube by isotonic contraction that
      results in displacement of the medial tubal cartilage and the tubal membrane, (2)
      the tensor veli palatini opens the tube directly by traction on the lateral tubal
      membrane and indirectly by rotation of the medial tubal cartilage by means of
      traction on the lateral tubal cartilage, (3) because of its consistently small
      size, the salpingopharyngeus is probably functionally the least important of the
      paratubal muscles, (4) the levator veli palatini is unable to cause tubal
      dilatation in cleft palate because it can only contract isometrically, and (5)
      tensor veli palatini function is probably unaffected by clefting. However, its
      mechanism of action may be disrupted iatrogenically by complete hamular fracture
      or division of its tendon.

PMID- 9290648
TI  - Cloning and expression of an Arabidopsis gene encoding a putative peroxisomal
      ascorbate peroxidase.
AB  - An Arabidopsis 14-3-3 protein, AFT1, was used as a 'bait' in the two-hybrid
      system to identify its interacting proteins. One of the candidate proteins, APX3,
      was identified as a putative peroxisomal membrane-bound ascorbate peroxidase.
      Ascorbate peroxidases are important defense enzymes that protect plant cells from
      oxidative stress damage. DNA blot analysis indicates that APX3 is encoded by a
      single-copy gene in the Arabidopsis genome. RNA blot analyses show that APX3
      transcript levels increase slightly in response to cold, UV light, and treatments
      with hydrogen peroxide and paraquat. The activity of APX3 in Arabidopsis may be
      controlled in two ways: its enzymatic activity through protein-protein
      interactions and its transcription by transcriptional or posttranscriptional
      regulation.

PMID- 9290651
TI  - Blood supply of the Le Fort I maxillary segment: an anatomic study.
AB  - The vascular supply of the Le Fort I osteotomy segment was studied by utilizing
      standard latex injection techniques. Anatomic dissections in 10 fresh cadavers
      demonstrated interruption of the descending palatine arteries with preservation
      of the ascending palatine branch of the facial artery and the anterior branch of
      the ascending pharyngeal artery within the attached posterior palatal soft-tissue
      pedicle in all specimens following Le Fort I maxillary osteotomy. These ascending
      arterial branches entered the soft palate at a position approximately 1 cm
      posterior to the pterygomaxillary junction, which was disrupted during the Le
      Fort I maxillary osteotomy. Separate ink injections of total maxillary osteotomy
      segments confirmed vascular perfusion of the ipsilateral hemimaxillary segment by
      the ascending palatine artery. Thus vascular supply of the mobilized Le Fort I
      maxillary segment is by means of the ascending palatine branch of the facial
      artery and the anterior branch of the ascending pharyngeal artery in addition to
      the rich mucosal alveolar anastomotic network overlying the maxilla.

PMID- 9290652
TI  - Simultaneous mandibular and maxillary distraction in hemifacial microsomia in
      adults: avoiding occlusal disasters.
AB  - Mandibular elongation by gradual distraction in patients with hemifacial
      microsomia is a simple and effective procedure to correct facial asymmetry. The
      two-pin system joined by a softer distracting screw achieves elongation in
      vertical and sagittal directions as well as medial rotation. The changes in
      mandibular shape result in changes in dental occlusion. These are minimal in
      children because of the rapid growth of the maxilla and can be corrected easily
      with minor orthodontic work. Mandibular distraction in adults with hemifacial
      microsomia, who usually have stable dental occlusion, produces good aesthetic
      results but also severe alterations in the occlusion requiring complex
      orthodontic treatment over a long period. To avoid this problem, an incomplete Le
      Fort I osteotomy is done simultaneously with the mandibular corticotomy.
      Intermaxillary fixation is done on the fifth postoperative day, and distraction
      is initiated. In a series of seven patients, the maxilla was distracted
      simultaneously with the mandible, preserving the preexisting stable occlusion.
      Preoperative deviation of the occlusal plane from the horizontal varied from 12
      to 18 degrees. The plane became horizontal in four patients, and deviation of 2
      degrees persisted in three. The distance from the inferior orbital rim to the
      occlusal plane on the affected side was increased in all patients, achieving 100
      percent correction (compared with the normal side) in four patients and 95, 96,
      and 97 percent in the other three.

PMID- 9290653
TI  - Infections in craniofacial surgery: a combined report of 567 procedures from two
      centers.
AB  - This retrospective review of infectious complications was undertaken at two
      craniofacial centers (Dallas and Philadelphia). Fourteen infections were
      identified over a 6.5-year period in 567 intracranial procedures primarily for
      craniosynostosis. There were no infections in infants under 13 months of age and
      no cases of meningitis. The overall infection rate was 2.5 percent, and 85
      percent of infections occurred in secondary reoperative cases. Tracheostomies
      were not identified as a risk factor for infection. No difference was found in
      infection rates between patients with shaved and unshaved scalps. Candida and
      Pseudomonas were the two most common organisms identified, and 28 percent of our
      infections involved yeast. The average time to diagnose infection was 11.5 days
      (excluding three patients who averaged 5 months). Thirteen of the fourteen
      infections were treated surgically with placement of a subgaleal
      irrigation/drainage system. Initial bony debridement was kept to a minimum. Based
      on our findings, recommendations are made to further lower infection rates,
      particularly those caused by opportunistic organisms.

PMID- 9290654
TI  - The use of porous granular hydroxyapatite in secondary orbitocranial
      reconstruction.
AB  - The search for the ideal bone-graft substitute has been the focus of many
      research and clinical studies. Hydroxyapatite is one such material that combines
      osseointegration with maintenance of implant volume and excellent durability. We
      present our experience in 29 patients ranging in age from 3 to 22 years (mean age
      10.5 years) who underwent secondary orbitocranial reconstruction of large contour
      defects utilizing porous granular hydroxyapatite. Follow-up ranges from 6 to 72
      months (mean 30 months). Indications for secondary surgery included residual bony
      contour defects of the frontal bone, temporal areas, and superior orbital rims
      that were present 12 months or more after initial surgery. There was one
      infection secondary to a chronic seroma necessitating removal of the porous
      hydroxyapatite, and one patient required revision for underfilling and another
      for overfilling. Excellent permanent contour improvement was obtained with a
      smooth skin surface in the remainder of our patients. The contour corrections
      have been long lasting, without evidence of porous hydroxyapatite resorption or
      migration.

PMID- 9290655
TI  - Reduction mammaplasty: an outcome study.
AB  - Outcome studies of the value of reduction mammaplasties have only recently
      appeared in the literature. Medical directors of insurance companies and managed
      care plans have been reluctant to pay for reduction mammaplasties, citing the
      uncertainty of the medical necessity of the procedure. They have defended their
      position by stating that the medical literature is devoid of studies documenting
      that reduction mammaplasty is medically beneficial to the patient. For this
      reason, reduction mammaplasty is often excluded from health care benefit plans.
      Because of the need for outcome studies for this procedure, the charts of 363
      consecutive patients who had reduction mammaplasty at the Mayo Clinic from
      January of 1986 to December of 1993 were reviewed. Questionnaires were sent to
      all these patients asking them to evaluate their outcome, and 328 responded (90.4
      percent response rate). Of the respondents, 94.2 percent believed that the
      procedure was completely or very successful, and only 1.5 percent believed that
      it was not very successful or completely unsuccessful. The symptoms most
      frequently reported by patients preoperatively were as follows: uncomfortable
      feeling about their body, 97.0 percent: inability to find clothes that fit, 95.7
      percent; pain in bra-strap groove, 92.4 percent; shoulder pain, 86.0 percent;
      inability to run, 79.3 percent; upper back pain, 79.0 percent; inability to
      participate in sports, 77.4 percent; neck pain, 70.7 percent; lower back pain,
      64.0 percent; and intertrigo, 61.0 percent. The symptoms least frequently
      reported by patients preoperatively were as follows: pain or numbness in the
      hands, 22.6 percent; headaches, 30.2 percent; arm pain, 35.4 percent; and breast
      pain, 58.2 percent. These symptoms were either relieved or partially relieved in
      88 percent or more of the patients. Of the 328 patients, 97.3 percent responded
      that they definitely or probably would have the procedure again, and only 1.2
      percent definitely or probably would not have the operation again. Evaluation of
      medical treatment used to relieve symptoms showed a marked decrease in the need
      for such measures after reduction mammaplasty. Study of the charges for the
      procedure revealed that the setting of practice parameters for the procedure and
      the use of an ambulatory surgery center significantly decreased the charges for
      the procedure. This outcome study supports the hypothesis that reduction
      mammaplasty is an effective procedure and the treatment of choice for symptomatic
      mammary hyperplasia.

PMID- 9290656
TI  - Surgical treatment of dermatofibrosarcoma protuberans.
AB  - Dermatofibrosarcoma protuberans is a rare dermal tumor that recurs after
      inadequate primary treatment. In a retrospective study, we analyzed the outcomes
      of 117 patients (mean age 39 years) treated surgically for a dermatofibrosarcoma
      protuberans. In most cases (107 patients), surgery was performed according to a
      protocol of taking wide peripheral resection margins of 5 cm and by resecting a
      disease-free anatomic zone deep to the lesion. The mean follow-up was 61 months.
      The results suggest a difference in prognosis between patients treated primarily
      with wide initial resection and those referred secondarily with recurrent disease
      following previous treatment by narrow resection margins. There was no recurrent
      disease in the 66 patients treated primarily by wide peripheral (5 cm) and deep
      resection of the tumor. Of the 41 patients referred secondarily at the time of
      recurrence, 2 developed further local disease within a year, despite equally
      aggressive local treatments. Both patients eventually died of metastatic
      fibrosarcoma. We emphasize the value of a highly aggressive local resection in
      the primary treatment of dermatofibrosarcoma protuberans to minimize local
      recurrence and potential malignant transformation. Modern reconstructive
      techniques provide satisfactory solutions for defects of almost any size and
      composition. Our findings suggest that radical primary resection of
      dermatofibrosarcoma protuberans in conjunction with immediate reconstruction of
      the primary defect provides the best outcome for the patient.

PMID- 9290657
TI  - Nonoperative estimation of the soleus musculotendinous junction using magnetic
      resonance imaging.
AB  - Although it is recognized as the muscle flap of choice for middle-third defects
      of the lower limb, the capability for even more distal transposition of the
      soleus muscle remains controversial. Such reach depends directly on the site of
      insertion of the muscle and previously has not been assessed convincingly without
      surgical intervention. Magnetic resonance imaging (MRI) may be a noninvasive
      alternative for determining the distal extent of the musculotendinous junction of
      the soleus muscle. In our last four patients, preoperative MRI scans were
      obtained prior to an elective soleus muscle transfer. The distance from the ankle
      joint to the most distal site of the soleus insertion was measured on the MRI
      scan and compared with the actual intraoperative measurement, which had a
      significant correlation (r = 0.98, p = 0.019). A retrospective review of 42 other
      sagittal ankle MRI scans predicted the mean of this distance to be 1.92 +/- 1.23
      cm (range -0.4 to 4.5 cm), compared with gross anatomic dissections in 30
      unrelated fresh cadavers, where this was 4.06 +/- 3.11 cm (range -0.7 to 12.5
      cm). These additional data are pertinent because they reinforce recognition of
      the great variation in soleus anatomy, which would limit clinical applications
      for the distal third of the leg only for those individuals with very distal
      insertions. The MRI scan can reliably identify the soleus muscle and provides a
      nonoperative method for evaluation of potential feasibility for its use as a
      local muscle flap for distal lower extremity defects.

PMID- 9290658
TI  - Experimental study on donor nerves for brachial plexus injury: comparison between
      the spinal accessory nerve and the intercostal nerve.
AB  - The spinal accessory nerve and intercostal nerves are widely used as donor nerves
      for neurotization in patients with brachial plexus injuries. However, the
      characteristic differences in reinnervation by the spinal accessory and
      intercostal nerves have not been investigated. The purpose of this study is to
      compare the resulting contractile properties of the biceps muscles following
      nerve-crossing procedures of spinal accessory nerve and intercostal nerves to the
      musculocutaneous nerves. In 10 beagle dogs, the spinal accessory nerve was used
      to reinnervate the left biceps muscle, and the second and third intercostal
      nerves were used to reinnervate the right biceps muscle. After 10 months, the
      reinnervated muscles were studied by measuring their force of contraction as well
      as by histochemical methods. Biceps muscles reinnervated by spinal accessory
      nerves (A transfers) acquired the properties of fast, fatigable muscles, whereas
      those reinnervated by intercostal nerves (IC transfers) acquired the properties
      of slow, fatigue-resistant muscles. Furthermore, histochemical studies showed
      that type II fibers were predominant in A transfers, whereas type I fibers were
      predominant in IC transfers. This study clearly demonstrates the differences
      between the spinal accessory nerve and intercostal nerves as donor nerves. This
      may lead us to select appropriate donor nerves for nerve-crossing procedures and
      free-muscle transfer depending on the desired functions to be reconstructed.

PMID- 9290659
TI  - A new flap from the dorsum of the first intermetacarpal area: the first dorsal
      intermetacarpal flap.
AB  - Soft-tissue reconstruction of the hand still remains a challenge for plastic and
      reconstructive surgeons. Several flaps have been described to cover soft-tissue
      defects of the digits and the hand. In the first web region, there are some
      communications between the intermediate artery arising from the dorsal branch of
      the radial artery and the volar arteries of the thumb and the index finger.
      Depending on these communications, a new distally based flap is raised from the
      first dorsal intermetacarpal area. This flap has been used to cover various
      defects of the thumb in four patients and the distal radial side of the palmar
      area in one patient. Donor sites have been closed primarily except in one
      patient. There were no complications, and the results show that this flap is
      useful to cover soft-tissue defects of the thumb and proximal phalanx of the
      index finger as well as the radial side of the palmar and dorsal surfaces of the
      hand.

PMID- 9290660
TI  - Island fasciocutaneous flap based on the proximal perforators of the radial
      artery for resurfacing of burned cubital fossa.
AB  - In the vast majority of burned patients, the injury is limited to the skin and
      superficial subcutaneous tissue, and the vasculature of the deeper fascia is
      spared. This fact encouraged me to design a flap in which the burned scar tissue
      is employed. The island fasciocutaneous flap is based only on the proximal
      septocutaneous perforators of the radial artery. The flap is used to resurface
      the anterior as well as the lateral burned cubital fossa after excision of the
      scar tissue and release of contracture. An anatomic study as well as clinical
      approach has been conducted.

PMID- 9290661
TI  - Surgical treatment of large cutaneous lesions of the back in children by
      concentric cutaneous mobilization.
AB  - Excision of large cutaneous lesions of the back, such as giant nevi in children,
      represents a major surgical challenge. Actually, many authors use tissue
      expanders. Recently, we have proposed, through a better evaluation of the
      biomechanical properties of the skin, a natural expansion mode using the
      postoperative tension. This expansion is natural and delayed. In the back the
      natural expansion can be created by concentric excision, which takes maximum
      advantage of the possibilities of cutaneous mobilization of the back. The
      concentric excision has been used in 12 children presenting with cutaneous
      lesions of the back involving more than 30 percent of the dorsal anatomic unit.
      Nine patients underwent total excision; two patients were treated in one stage,
      four patients in two stages, and three patients in three stages. Three patients
      could not have total excision. The follow-up was uneventful, except in one
      patient who presented with wound dehiscence. The follow-up was 1 to 2 years and
      showed a modest scar widening (< 4 mm) in three patients, moderate widening (> 4
      min, < 7 mm) in three patients, and significant widening (> 10 mm) in three
      patients. The systematization of the cutaneous mobilization for each region of
      the back has allowed us to optimize the utilization of peripheral normal tissue
      in the surgical treatment of large cutaneous lesions of the back. In some
      circumstances, the gain in tissue has been superior to that we usually obtain
      with skin expanders and with lesser cost, lesser pain, and fewer risks.

PMID- 9290662
TI  - Gene expression of transforming growth factor beta-1 in rabbit zone II flexor
      tendon wound healing: evidence for dual mechanisms of repair.
AB  - The postoperative outcome of hand flexor tendon repair can be complicated by
      adhesions between the repair site and surrounding tissue. To date, the biology of
      hand flexor tendon wound healing remains controversial--both intrinsic (resident
      tenocyte) and extrinsic (tendon sheath fibroblast and inflammatory cell)
      processes may contribute to repair. Transforming growth factor beta-1 is a
      cytokine that plays multiple roles in wound healing but is also implicated in the
      pathogenesis of excessive scar formation. This study examines the activation of
      transforming growth factor beta-1 mRNA in a rabbit zone II flexor tendon wound
      healing model. Forty New Zealand White rabbit forepaws underwent complete
      transection and repair of the middle digit flexor digitorum profundus tendon in
      zone II. Tendons were harvested at increasing time intervals (1, 3, 7, 14, 28,
      and 56 days) and analyzed by in situ hybridization and immunohistochemistry to
      determine the expression patterns of transforming growth factor beta-1. A small
      number of tenocytes exhibited expression of transforming growth factor beta-1
      mRNA at baseline in nonwounded control tendon specimens. The surrounding tendon
      sheath in these control specimens also revealed low numbers of fibroblasts and
      inflammatory cells expressing transforming growth factor beta-1 mRNA. In
      contrast, flexor tendons subjected to transection and repair exhibited increased
      signal for transforming growth factor beta-1 mRNA in both resident tenocytes and
      infiltrating fibroblasts and inflammatory cells from the tendon sheath. These
      data demonstrate that (1) normal unwounded tenocytes and tendon sheath cells are
      capable of transforming growth factor beta-1 production, (2) this cytokine is
      activated in the tendon wound environment, as evidenced by mRNA upregulation, and
      (3) the upregulation of this cytokine in both "intrinsic" tenocytes and
      "extrinsic" tendon sheath fibroblasts and inflammatory cells supports dual
      mechanisms for tendon repair. Because transforming growth factor beta-1 is
      thought to contribute to the pathogenesis of excessive scar formation, the
      findings presented here suggest that perioperative biochemical modulation of
      transforming growth factor beta-1 levels may help limit flexor tendon adhesion
      formation.

PMID- 9290663
TI  - Effects of extradural anesthesia on microcirculatory blood flow in free
      latissimus dorsi musculocutaneous flaps in pigs.
AB  - Free musculocutaneous flaps are used frequently in plastic surgery to reconstruct
      soft-tissue defects after radical cancer surgery and trauma. Despite improved
      surgical techniques, some of these flaps fail due to insufficient blood supply.
      Extradural anesthesia causes both sensory (pain relief) and sympathetic
      (vasodilatation) block that may be advantageous in free-flap surgery. This
      hypothesis, however, has not yet been studied. An experimental model in pigs was
      developed in which clinical conditions for anesthesia and microvascular surgery
      on the lower extremity were simulated as closely as possible. The effects of
      extradural anesthesia as well as phenylephrine infusion, combined with general
      anesthesia, on central hemodynamics and on microcirculatory blood flow in skin
      and muscle of the latissimus dorsi free flap were studied. After surgery, seven
      animals received extradural anesthesia during stable normovolemic conditions and
      another seven during mild hypovolemia (10 percent blood loss). The extradural
      block was objectively evaluated using the temporal summation test. Thirty minutes
      after induction of extradural anesthesia, the animals received an intravenous
      infusion of phenylephrine 1 microgram/kg per minute over a period of 15 minutes.
      Multichannel laser-Doppler flowmetry was used to measure microcirculatory blood
      flow in skin and muscle of the free flap as well as in control skin and muscle on
      the same extremity simultaneously. In normovolemic animals, extradural block
      caused a 10 percent decrease in mean arterial pressure and cardiac output and an
      approximately 20 percent decrease in microcirculatory blood flow in both the skin
      and muscle of the flap (all changes were nonsignificant). In slightly hypovolemic
      animals, however, extradural anesthesia caused a significant decrease in cardiac
      output (31 percent, p < 0.01), mean arterial pressure (24 percent, p < 0.01), and
      in mean blood flow in the flap muscle (22 percent, p < 0.05) and skin (20
      percent, p < 0.05). During phenylephrine infusion, mean arterial pressure
      increased significantly (p < 0.05) in both hypovolemic and normovolemic animals,
      while cardiac output and microcirculatory blood flow in the flap remained almost
      unchanged. Extradural anesthesia does not improve microcirculatory blood flow in
      free musculocutaneous flaps in pigs. It causes a significant decrease in cardiac
      output, mean arterial pressure, and microcirculatory blood flow in slightly
      hypovolemic animals. During phenylephrine infusion, the microcirculatory blood
      flow in free flaps slightly improves due to the increase in mean arterial
      pressure. We suggest that extradural anesthesia for microvascular surgery should
      be used with great caution until human data are available.

PMID- 9290664
TI  - Improved preservation of rat hindlimbs with the University of Wisconsin solution
      and butanedione monoxime.
AB  - The purpose of this study was to compare the effects of the University of
      Wisconsin solution plus butanedione monoxime, the University of Wisconsin
      solution without butanedione monoxime, and saline on the preservation of muscle
      tissue. Forty-nine rat hindlimbs were amputated and replanted. The study
      population was subdivided into four groups according to flushing solution,
      storage, and replantation protocols. The limbs of the control group (n = 12) were
      flushed with 20 ml University of Wisconsin solution and immediately replanted
      onto the same rat. In the remaining three groups, the limbs were immersed in
      solution, stored in a refrigerator at 4 degrees C for 24 hours, and then
      replanted onto a fresh rat. The limbs in the no flushout group (n = 7) were
      placed into storage in cold saline solution without being flushed. The limbs in
      the University of Wisconsin solution group (n = 17) were flushed with 20 ml of
      University of Wisconsin solution prior to storage, and those in the University of
      Wisconsin solution plus butanedione monoxime group (n = 13) were flushed with 20
      ml University of Wisconsin solution plus 20 mM butanedione monoxime. Limb
      survival rate was 100 percent for the control and University of Wisconsin
      solution plus butanedione monoxime groups, 87 percent for the University of
      Wisconsin solution group, and 71 percent for the no flushout group. Seven days
      after replantation, ATP levels were 71 percent of control in the University of
      Wisconsin solution plus butanedione monoxime group, 33 percent in the University
      of Wisconsin solution group, and 29 percent in the no flushout group. Tissue
      K+/Na+ ratio showed that the University of Wisconsin solution plus butanedione
      monoxime group maintained electrolyte balance, whereas the balance was
      significantly lowered in University of Wisconsin solution and no flushout groups.
      The University of Wisconsin solution plus butanedione monoxime limbs did not
      exhibit cell swelling, whereas total tissue water values for the University of
      Wisconsin solution and no flushout groups increased significantly. Serum
      creatinine kinase, measured 24 hours after replantation, was 120 percent of
      control in the University of Wisconsin solution plus butanedione monoxime group,
      550 percent in the University of Wisconsin solution group, and 772 percent in the
      no flushout group. Limbs in the University of Wisconsin solution plus butanedione
      monoxime group had more flexible ankle joints and pliable muscle (i.e., less
      contracture) than those in the University of Wisconsin solution and no flushout
      groups. In conclusion, rat hindlimbs can be preserved hypothermically for 24
      hours using the University of Wisconsin solution, the University of Wisconsin
      solution plus butanedione monoxime, or saline. However, the University of
      Wisconsin solution plus butanedione monoxime limbs had better ATP levels and less
      cellular injury after replantation. Based on these results, we believe that,
      biochemically, flushing and storage of muscle tissue in the University of
      Wisconsin solution plus butanedione monoxime are the most effective means of
      those studied for preserving composite tissue grafts for 24 hours.

PMID- 9290665
TI  - A comparative study of the effect of ultrasound and electrostimulation on wound
      healing in rats.
AB  - A comparative study has been carried out to investigate the effects of electrical
      stimulation and ultrasound on wound healing. Eighty-four female rats were divided
      into four groups depending on the treatment received. The first group was given
      electrical stimulation of 300 microA direct current, 30 minutes daily, starting
      with negative polarity and then changed after 3 days of treatment. Group 2
      received sham electrostimulation treatment. The third group received 0.1 W/cm2
      pulsed ultrasound using the moving applicator technique for 5 minutes a day.
      Group 4 received sham ultrasound treatment. A total of 7 days of treatment was
      given to all groups. Histopathologic and biochemical analyses on the fourth and
      seventh days and wound breaking strength on the twenty-fifth day were performed
      for all groups. By accelerating the inflammatory phase, electrical stimulation
      had progressed the proliferative phase of wound healing earlier than ultrasound
      had done. Both electrical stimulation and ultrasound have positive effects on
      proliferative phases, but electrical stimulation was superior to ultrasound at
      the maturation phase. There was no difference between the two experimental groups
      on the mast cell reduction effect. Although ultrasound treatment may seem to be
      efficient in terms of time, when the effects of electrical stimulation and
      ultrasound on wound healing with the methods employed in our study are
      considered, it is concluded that electrical stimulation is a means of treatment
      superior to ultrasound in wound healing.

PMID- 9290666
TI  - Modulation of ultraviolet light-induced epidermal damage: beneficial effects of
      tocopherol.
AB  - Oxygen free radicals have been shown to result from and mediate deleterious
      effects of ultraviolet radiation on the skin. The purpose of this study was to
      determine if topical DL-alpha-tocopherol (vitamin E) could reduce ultraviolet
      induced damage to the epidermis. Twenty mice were treated with either ethanol or
      a 1:1 mixture of tocopherol and ethanol. Treatments consisted of once-daily 0.1
      ml topical applications for 1 week, followed by irradiation with 0.30 mW/cm2 of
      ultraviolet B irradiation. A statistically significant decrease in Schiff base
      formation was noted between tocopherol-treated animals and their controls.
      Histologic study revealed a statistically significant increase in epidermal
      thickness in tocopherol-treated skin versus controls or vehicle alone. The
      thicker epidermis was accompanied by the presence of parakeratosis, implicating
      increased proliferation as the cause of the increasing thickness. The number of
      sunburn cells was decreased by tocopherol treatment. Tocopherol protection from
      ultraviolet irradiation may have been due to both direct protection from free
      radicals and indirect protection by means of increased epidermal thickness. The
      demonstration of beneficial effects of tocopherol administration suggests that
      further studies in clinically relevant models to define optimal dosage, frequency
      of administration, vehicle, and quantitation of the possible protective effects
      afforded to Langerhans cells may be useful.

PMID- 9290667
TI  - Partial failure of a free flap salvaged by using the surviving portion as a
      "bridge" flap for revascularizing a second free flap.
AB  - Partial failure of a free flap can create an unusual dilemma, as guidelines
      suggesting appropriate further intervention are not well defined. The increased
      complexity of a second free flap attempt is not necessarily contraindicated, but
      must be minimized if the same fate as the first is to be avoided. For the unique
      circumstance where the initial failed flap contained a vascular flow-through, the
      most distal patent vessels can then secondarily serve in an expeditious manner as
      the recipient vessels for the second or salvage free flap. The efficacy of this
      concept has been here validated after limited necrosis occurred in the distal
      portion of a radial forearm free flap. Following the requisite debridement, the
      residual flap still maintained a satisfactory arterial and venous flowthrough as
      a "bridge flap" that supported the attachment of a gracilis muscle free flap, and
      both flaps in turn preserved a sensate transtarsal amputation stump.

PMID- 9290668
TI  - Composite osteoarthrotenocutaneous free flap from the foot for reconstruction of
      an unusual hand wound.
AB  - A case of a single-stage reconstruction of the left hand of a 32-year-old right
      handed construction worker with a shotgun wound by means of a composite
      osteoarthrotenocutaneous free flap from the foot is presented. The tissue loss
      caused by the injury included the cutaneous coverage of the dorsum of the left
      hand, extensor tendons of the second, third, fourth and fifth digits, metacarpals
      of the same fingers, and the second and third metacarpophalangeal joints. After 8
      years of evolution, we have been able to verify a valuable degree of functional
      capability of the reconstructed hand.

PMID- 9290669
TI  - A trilobed flap for reconstruction of nasal skin defects.
AB  - We developed a trilobed flap, i.e., a Dufourmentel flap connected to two
      continuous triangular flaps whose angles are decreased by one-quarter. We used
      this type of flap in eight patients with nasal skin defects, sequelae of
      tumorectomy, and obtained good results.

PMID- 9290670
TI  - The V-Y advancement myotarsocutaneous flap for upper eyelid reconstruction.
AB  - The V-Y advancement myotarsocutaneous flap was used to avoid excessive scarring
      during reconstruction of a full-thickness upper eyelid defect following surgical
      excision of a malignant tumor. This method has a number of advantages: It has a
      short operative time, it is a one-stage procedure, it does not require lining by
      auricular or septal cartilage, the technique is relatively simple, and the scar
      is inconspicuous, since both flap margins are placed in skin creases. The V-Y
      myotarsocutaneous flap is best suited for the repair of full-thickness upper
      eyelid defects ranging from 25 to 50 percent of the lid width when the remaining
      lateral canthal structures are adequate to support the flap.

PMID- 9290671
TI  - Septal extension grafts: a method of controlling tip projection shape.
AB  - Failure to control the projection, shape, and rotation of the nasal tip is a
      common occurrence among patients with weak lower lateral cartilages. These
      patients' noses are characterized by a weak midvault, a plunging tip with "Polly
      beak," and drawn-up alae. The purpose of our study was to identify methods for
      controlling the position and shape of the nasal tip in these high-risk patients.
      Twenty patients at risk of losing nasal tip projection were retrospectively
      identified, and measurements made from their preoperative and postoperative
      photographs were compared. Loss of tip projection occurred in all but one patient
      whose columella strut was fixed to the caudal septum. Prompted by these failures,
      we studied the relationship between the dorsum and tip in cadaveric specimens
      with and without a supratip break. From our observations, a structural extension
      of the septum-an anterior septal extension graft-was developed to predictably
      control this relationship. The clinical application of septal extension grafts in
      open rhinoplasty was subsequently evaluated in 20 patients who were deemed to be
      at risk of losing tip projection. Postoperative photographic analysis showed
      nasal tip projection to be maintained or increased in all but one patient with
      the use of septal extension grafts. A stable caudal septum is essential to the
      success of the technique.

PMID- 9290672
TI  - The contribution of the SMAS to the blood supply in the lateral face lift flap.
AB  - The purpose of this study was to compare the arterial blood supply of the lateral
      face lift flap when the flap is elevated either above or below the SMAS. The
      transverse facial artery supplies blood to a large portion of the lateral face
      lift flap. This vessel passes through the superficial musculoaponeurotic system
      (SMAS) in its course toward the flap. The transverse facial artery is at risk for
      transection during both elevation of the skin flap and elevation of the SMAS.
      Nine fresh cadavers underwent a single-plane rhytidectomy either superficial to
      the SMAS or in a sub-SMAS plane. In half the subjects, the transverse facial
      artery perforator was identified prior to dissection using surface landmarks and
      preserved. In the other half of dissected specimens, this perforator was
      transected by undermining through the transverse facial artery perforation site
      (near the zygomatic ligament). This transection is typically performed during a
      face lift. The facial artery and transverse facial artery were selectively
      injected with ink, and cutaneous staining was recorded. It was found that the
      pattern and total area of ink staining occurred in an all-or-none fashion
      depending on whether the transverse facial artery had been preserved or
      transected. Inclusion or exclusion of the SMAS layer in the dissected lateral
      face lift flap had no effect on the ink injection pattern, suggesting that the
      SMAS plays little or no role in lateral face lift flap viability.

PMID- 9290673
TI  - Saline-filled breast implants: a Plastic Surgery Educational Foundation
      multicenter outcomes study.
AB  - In 1993, the Plastic Surgery Educational Foundation commissioned the senior
      author (Cunningham) to design an 11-center retrospective cohort outcomes study to
      obtain physician- and patient-reported data on saline-filled breast implants.
      Data were obtained from 504 patients with 995 saline-filled breast implants
      placed between January 1, 1980 and December 31, 1989, with a mean follow-up of 6
      years. Most (93.8 percent) saline-filled breast implants were placed for breast
      augmentation. Of the 504 patients, 104 (20.6 percent) required reoperation for
      open capsulotomy or for replacement or removal of a deflated implant.
      Complications occurred in 22 patients (4.4 percent), with hematoma being most
      common. Implant deflation occurred in 55 implants (5.5 percent) and affected 51
      patients (10.1 percent) but was underreported by chart abstraction alone. Risk
      factors for implant deflation included underfilling the implant by more than 25
      cc (odds ratio 3.3, p = 0.0400), the use of model 1800 saline-filled breast
      implants (odds ratio 3.1, p = 0.0010), intraluminal antibiotics (odds ratio 2.6,
      p = 0.0183), and intraluminal steroids (odds ratio 2.4, p = 0.0711). Based on 44
      of 55 saline-filled breast implants with known deflation dates, actuarial
      survival is 95.7 to 98.0 percent at 5 years and 90.2 to 95.2 percent at 10 years
      (95 percent confidence interval). Significant periprosthetic capsular contracture
      affected 103 patients (20.4 percent) during follow-up. Risk factors for capsular
      contracture included omitting intraluminal antibiotics (odds ratio 16.7, p =
      0.0001), omitting intraluminal steroids (odds ratio 12.5, p = 0.0001), submammary
      placement of the saline-filled breast implant (odds ratio 7.8, p = 0.0001), and
      use of antibiotics in the implant pocket (odds ratio 6.1, p = 0.0001). Overall
      patient satisfaction with saline-filled breast implants was rated as high by 94.2
      percent, and 94.8 percent of patients would choose saline-filled breast implants
      again. Dissatisfaction with their saline-filled breast implants was more frequent
      in patients with significant breast firmness (odds ratio 22.9, p = 0.0001), those
      undergoing prophylactic mastectomy (odds ratio 8.2, p = 0.0005), and those
      desiring smaller implants (odds ratio 6.9, p = 0.0001). In conclusion, saline
      filled breast implants are a safe alternative to silicone gel-filled breast
      implants and demonstrate a high rate of patient satisfaction. Underfilling of
      saline-filled breast implants should be avoided because it contributes to
      deflation. Although intraluminal antibiotics and steroids protect against
      capsular contracture, they also contribute to saline-filled breast implant
      deflation. The incidence of capsular contracture is decreased by placing the
      saline-filled breast implant in the subpectoral position. Finally, patients
      should be aware of the possible need for reoperations related to their implants.

PMID- 9290674
TI  - Incidence and natural history of saline-filled breast implant deflations:
      comparison of blunt-tipped versus cutting and tapered needles.
AB  - The silicone shells of breast implants are known to fail. When failure occurs in
      saline-filled implants, the consequences are always ultimately symptomatic.
      Failure may be due to shell elastomer fatigue, fold-flaw cracking, faulty valve
      mechanisms, trauma, and microperforations (defined as perforations that are too
      small to be seen with the unassisted eye). To determine the incidence and natural
      history of microperforations, a major manufacturer of saline-filled breast
      implants was contacted. Over a 30-month period, 289,033 saline implants were
      sold, and 2844 were subsequently returned due to perioperative deflation. By
      using a rigorous and reproducible method of evaluating returned deflated saline
      filled breast implants, it was found that 197 (0.068 percent of all implants
      sold) sustained needle damage at the time of insertion and went on to deflate
      within 6 months. Of the implants returned, overall 6.93 percent were found to
      have sustained needle trauma as the cause of the deflation, and the incidence
      appears to be increasing with time. The actual incidence of needle-related
      deflations may be significantly greater, since these data reflect only those
      implants which are voluntarily returned to the manufacturer. As a second part of
      this study, a segment of the silicone shell from a saline-filled breast implant
      was tested to determine the resistance to puncture using blunt-tipped, tapered,
      and cutting needles. The blunt-tipped needle required 6.6 times more force to
      puncture the shell than a cutting needle (p = 0.0011) and 3.2 times more force
      than a tapered needle (p = 0.0052). The difference in force needed to puncture
      the shell for a tapered and a cutting needle was not statistically significantly
      different (p = 0.5045). Microperforations do occur in the operating room and are
      responsible for a significant percentage of early (less than 6 months)
      deflations. Blunt needles require significantly more force to puncture the shell
      of an implant than do cutting and tapered needles, and their use may reduce the
      incidence of microperforations and subsequent implant deflations.

PMID- 9290675
TI  - Why I prefer the endoscopic forehead lift.
AB  - The objectives of the forehead lift and the surgical principles of the open
      versus the endoscopic methods have been outlined. The advantages and
      disadvantages of each method have been described. Based on this, I state without
      any reservations my preference for the endoscopic forehead lift because the
      advantages significantly outweigh the disadvantages. Based on these and on the
      enthusiasm of surgeons and the high degree of patient satisfaction and
      acceptability, I predict that the endoscopic method with its many variations will
      replace the traditional open approach as a first alternative for forehead lift
      and upper face rejuvenation.

PMID- 9290676
TI  - Open approach for upper facial rejuvenation.

PMID- 9290677
TI  - Suction lipectomy of the ankle area.
AB  - This article discusses the basic concepts of the aesthetics of the ankle area,
      emphasizing the lower limb's proportions, and looking for the greatest
      proportional fineness in this area. The normal ankle is schematized as if it were
      a rhomboid prism whose major axis is anteroposterior, and circumferential
      liposuction is discussed in order to avoid reproduction of the same ankle's
      lipodystrophic shapes. To do so, the roundness of the ankle is divided as if it
      consisted of the rectangular faces of a rhomboid prism to get the anatomic and
      aesthetic shapes of this area. The article also discusses the details of the
      anesthesic infiltration, the surgical technique, and ways to avoid any damage in
      the noble structures when liposuction is performed in the ankle area. This
      technique may be applied when the orthostatic axis of the lower limbs is
      deflected; it can be optically corrected in the leg or aligned through
      exaggerated liposuction of the convex lipodystrophic areas.

PMID- 9290678
TI  - Preparing for the twenty-first century.

PMID- 9290679
TI  - Will the real plastic surgeon please stand up?

PMID- 9290680
TI  - The Americans with Disabilities Act: should it compel cosmetic treatment for HIV
      positive individuals?

PMID- 9290681
TI  - Volcano cast to monitor revascularized digits.

PMID- 9290682
TI  - Immediate versus delayed lip reconstruction after dog bite lesions.

PMID- 9290683
TI  - Are soft-tissue sarcomas of the thigh particularly prone to thromboembolic
      phenomena?

PMID- 9290684
TI  - Medical research on dogs.

PMID- 9290685
TI  - Axillary lymphadenectomy: a diagnostic and therapeutic procedure.
AB  - Axillary dissection for primary operable cancer follows the basic tenants of
      surgical oncology and achieves the stated goals. Local control is excellent with
      failure rates in the 0-2% range. Long-term and disease-free survival is improved
      with axillary dissection. It is often stated that axillary dissection is not
      required for the smallest of lesions, but the 15% risk of axillary disease with
      the T1A lesion would suggest otherwise. Axillary sampling would not achieve the
      stated goals because of the high probability of retained, potentially resectable
      disease in the node positive group. Axillary recurrence is associated with an
      unacceptably high morbidity and mortality. Although the survival is similar in
      the three treatment groups of NSABP B-04, the inordinately high systemic failure
      rate with axillary recurrence would suggest that more aggressive local control
      could prevent many of these failures. After all, long-term survival free of
      disease is reported in many series even in patients with multiple involved nodes.
      Axillary dissection also generates the most accurate prognostic variable upon
      which further therapeutic interventions are predicated. At present there is no
      other diagnostic or therapeutic approach that achieves all of these goals. In
      summary the value of the axillary dissection is to provide accurate prognostic
      information as well as excellent local control and to improve the survival rate
      in the node positive group. It is hoped that in the future a diagnostic test such
      as PET scanning or sentinel node mapping may predict those patients with a clear
      axilla and therefore not require an axillary dissection. Finally, there has yet
      to be a primary operable carcinoma that benefits from preservation of potentially
      fully resectable disease.

PMID- 9290686
TI  - Case against axillary lymphadenectomy for most patients with infiltrating breast
      cancer.

PMID- 9290687
TI  - Antiproliferative effect of suramin on primary cultures of human
      pheochromocytomas and rat PC12 pheochromocytoma cells.
AB  - BACKGROUND: Suramin inhibits growth of neural crest-derived cells and is used to
      treat adrenocortical cancer and neuroblastoma in clinical trials. The
      antiproliferative effect of suramin was evaluated in primary cultures of human
      pheochromocytoma and the PC12 rat pheochromocytoma cell line in vitro and in
      vivo. METHODS: Human pheochromocytoma and PC12 rat pheochromocytoma cells were
      grown in medium supplemented with suramin at concentrations of 1-1,000
      micrograms/ml (1.43-1.43 mM) for up to five generations. Suramin did not induce
      neuronal differentiation, but inhibited growth of cultured human pheochromocytoma
      cells with IC50 (inhibitory concentration at which a 50% reduction of
      proliferation is observed) of 50-250 micrograms/ml. Also, suramin inhibited
      proliferation of PC12 cells with IC50 of 228 micrograms/ml after 5 days and 161
      micrograms/ml at 10 days of treatment. Colony formation assays demonstrated these
      effects to be cytotoxic rather than cytostatic. Thus when reproductive integrity
      of PC12 cells was taken into account, IC50 was calculated with 118 micrograms/ml
      and 129 micrograms/ml, respectively. In vivo experiments were performed with
      subcutaneously xenotransplanted PC12 cells (BALB/c NCR-NU mice). Suramin did not
      alter tumorigenicity and did not inhibit local tumor growth. RESULTS: These data
      determine for the first time an antiproliferative effect of suramin in
      pheochromocytoma cells. Suramin is cytotoxic to pheochromocytoma cells in vitro
      at levels that are clinically achievable. CONCLUSIONS: Suramin may have potential
      as an antiproliferative drug in nonresectable pheochromocytoma.

PMID- 9290688
TI  - Thoracic complications in patients undergoing intraperitoneal heated chemotherapy
      with mitomycin following cytoreductive surgery.
AB  - BACKGROUND: The purpose of this study was to determine the incidence and severity
      of thoracic reactions in patients undergoing intraperitoneal heated chemotherapy
      (IPHC). METHODS: Forty-two patients who had intraperitoneal disseminated
      malignancies were treated with cytoreductive surgery (CS) and IPHC. The primary
      malignancies included carcinoma of the colon (n = 17), stomach (n = 6), appendix
      (n = 6), pseudomyxoma peritonei (n = 3), mesothelium (n = 2), ovaries (n = 2),
      jejunum (n = 2), gallbladder (n = 1), urachus (n = 1), and peritoneal
      carcinomatosis (n = 2). After CS, IPHC with mitomycin (MMC) was administered by
      perfusion at 40.5 degrees C. After IPHC, multiple radiographs of the chest were
      reviewed in comparison to the control group. RESULTS: Thoracic complications
      occurred in 36 patients (86%), including atelectasis in 32 patients (76%),
      pleural effusions in 27 (64%), pulmonary edema in 10 (24%), pneumonia in 2 (5%),
      and pneumothorax in 2 (5%). The incidence of thoracic complications in the IPHC
      group was significantly higher than that of patients in the control group (P <
      .05). Correlations between the prevalence of pleural effusion and the dose of
      MMC, duration of procedure, and presence of thrombocytopenia were not significant
      (P > .05). CONCLUSIONS: Bibasilar atelectasis and pleural effusions are common
      findings after IPHC with MMC, but most of them do not necessarily warrant
      intervention.

PMID- 9290689
TI  - Patterns of failure and long-term results in high-risk resected gastric cancer
      treated with postoperative radiotherapy with or without intraoperative electron
      boost.
AB  - BACKGROUND: To evaluate the possible role of adjuvant radiotherapy in the
      management of high-risk resected gastric carcinoma. METHODS: From 1982 to 1993,
      62 patients surgically resected of a primary gastric cancer with adverse
      pathological features (serosal and/or regional lymph node involvement) were
      treated with postoperative radiotherapy with (Group I) or without (Group II)
      intraoperative electron boost to the surgical bed and coeliac axis (IORT).
      RESULTS: After a median follow-up of 75.6 months (range 4-120+) for IORT patients
      and 91.2 months (range 6-149+) for non-IORT patients, overall relapse rates for
      Group I and Group II patients were 44.5% and 48.6% and local-regional relapse
      rates were 11.1% and 20%, respectively. Actuarial survival rates projected at the
      maximum follow-up were 41% and 38% in Groups I and II, respectively. CONCLUSIONS:
      This retrospective analysis suggests a beneficial effect of adjuvant external
      radiotherapy in promoting local-regional control in high-risk resected gastric
      cancer.

PMID- 9290690
TI  - Interlaboratory variation in oxygen tension measurement by Eppendorf "Histograph"
      and comparison with hypoxic marker.
AB  - BACKGROUND AND OBJECTIVES: The median of pO2 values in tumor measured by
      Eppendorf "Histograph" with a needle-type electrode has been used as a prognostic
      indicator in cancer patients. However, it is not established that a pretreatment
      measured pO2 value can be used as a universal predictor of local control
      probability, because the variation in pO2 values, especially in hypoxic tissue,
      among institutes may not allow comparison of measured "absolute pO2 values." The
      purpose of this study was to examine the variation in oxygen tension measurement
      by Eppendorf "Histograph" among six laboratories using a single batch of mice and
      tumors and the same detailed protocol. These results were also compared to the
      immunohistochemical staining of 2-nitromidazole adducts. METHODS: C3H mice
      bearing FSaII murine fibrosarcoma subcutaneously were shipped to all
      laboratories, and the oxygen status in tumors and in normal subcutis was examined
      using Eppendorf "Histograph" and immunohistochemical hypoxic marker. RESULTS: All
      laboratories showed that the FSaII tumor was hypoxic with at least 77% of
      measured points under 10 mmHg in pO2 and with a median pO2 value less than that
      of normal subcutis. These results were further confirmed immunohistochemically.
      These findings are interpreted as evidence that the pO2 values measured by
      Eppendorf "Histograph" can be useful. However, the median values of tumor pO2
      varied from 1.5 mmHg to 5.6 mmHg among the laboratories, and pO2 of normal
      subcutis also varied from 28 mmHg to 38 mmHg. There were also significant
      differences in hypoxic fraction, defined as the fraction under a given oxygen
      partial pressure (i.e., under 2.5, 5, or 10 mmHg), among institutes. CONCLUSIONS:
      Caution needs to be exercised in using the absolute, median, or distribution of
      pO2 values measured by the Eppendorf "Histograph" to compare the data between
      laboratories or to predict the radiation response in an individual subject.

PMID- 9290691
TI  - Expression of ICAM-1 enhances in vivo lymphocyte adhesion in a murine
      fibrosarcoma.
AB  - BACKGROUND AND OBJECTIVES: ICAM-1 is essential for lymphocyte-endothelial cell
      interactions. We have demonstrated that increased expression of ICAM-1 in tumors
      results in an enhanced response to adoptive immunotherapy. We undertook this
      study to determine whether increased expression of ICAM-1 results in increased
      lymphocyte adhesion in vivo. METHODS: Parental MCA-105 tumor cells were
      cotransfected with ICAM-1 and the NeoR plasmid. A neomycin resistant clone
      (Cl149) was selected and increased expression of ICAM-1 confirmed by FACS
      analysis. Tumor fragments (MCA-105 or Cl149) were placed in a dorsal skin-fold
      chamber on day 0 in C57BL/6 mice. Lymphocytes were fluorescently labeled using
      0.5% acridine orange and activity recorded on videotape at 700x magnification.
      Lymphocyte activity was quantitated over 30 second intervals in postcapillary
      venules as either passing or rolling/sticking (R/S). The % R/S was calculated for
      each category and evaluated using chi 2 analysis. RESULTS: Whereas 38% of
      lymphocytes were classified as R/S in normal tissue, 32% were classified as R/S
      (P > .05) in the MCA-105 tumor. However, in the ICAM-1 transfected CL149, there
      was significantly greater R/S at 53% (P < .05). CONCLUSIONS: These data
      demonstrate increased lymphocyte adhesion in tumors with enhanced expression of
      ICAM-1 by direct in vivo observations and may partially explain the salutary
      effect of increased ICAM-1 expression on adoptive immunotherapy. This suggests
      the possible application of adhesion molecule expression in the cellular therapy
      of cancer.

PMID- 9290692
TI  - Postsurgical sequential methotrexate, fluorouracil, and leucovorin for advanced
      colorectal carcinoma: a preliminary study.
AB  - BACKGROUND AND OBJECTIVES: The present study compared the effects of sequential
      methotrexate and fluorouracil followed by leucovorin rescue (MFL), as an adjuvant
      chemotherapy versus a combination of tegafur (UFT) and mitomycin C (MMC), on
      patient survival and recurrence after surgery for colorectal carcinoma. METHODS:
      Between January 1990 and December 1995, a total of 46 patients with advanced
      colorectal cancer were treated postsurgically by adjuvant chemotherapy using MFL
      or UFT-MMC. Surgical treatment was performed according to standardized procedures
      for radical resection of colorectal cancer. The patients were stratified into two
      groups after surgery. The MFL regimen consisted of MTX (100 mg/m2) and 5-FU (600
      mg/m2) at hour 24, followed by leucovorin rescue. The UFT-MMC regimen consisted
      of MMC (12 mg/m2) intraoperatively and MMC (6 mg/m2) ever other week after
      surgery for 2 months and oral UFT (375 mg/m2/day), a combination of tegafur and
      uracil in a molar ratio of 1:4, was continued for 3 years or longer depending on
      the patients tolerance. RESULTS: The overall survival rates after surgery was
      significantly (P < 0.05) higher in the MFL than the UFT-MMC group. Recurrence
      rates were significantly lower in the MFL than the UFT-MMC Group, especially for
      liver recurrence. Disease-free survival was significantly (P < 0.05) higher in
      the MFL than the UFT-MMC group. CONCLUSIONS: The present results demonstrated the
      superiority of MFL therapy for improving postsurgical survival in patients with
      advanced colorectal cancer, in particular for those patients with a high risk of
      recurrence following potential curative resection.

PMID- 9290693
TI  - Appendiceal carcinoma: patterns of failure following surgery and implications for
      adjuvant therapy.
AB  - BACKGROUND AND OBJECTIVES: Primary adenocarcinoma of the appendix is rare, which
      makes an understanding of its natural history difficult. To date, it is treated
      predominantly with surgery alone. This review aims to elucidate the patterns of
      failure and treatment outcomes when adjuvant treatment is given after primary
      surgical resection. METHODS: Twenty-three patients were treated with either
      surgery alone, or with surgery and adjuvant radiation +/- chemotherapy. A review
      of the clinical course of these patients was undertaken with an analysis of the
      local control, distant failure, disease-free survival, and overall survival.
      RESULTS: Most patients presented with local invasion or metastatic disease often
      involving the peritoneum. Overall survival was 32%, similar to the results of
      other studies. Analysis of patients with locally advanced disease showed
      improvement in overall survival and local control with postoperative radiation
      therapy compared to surgery alone. CONCLUSIONS: Adenocarcinoma of the appendix is
      a rare disease that presents most often in an advanced stage. It has been shown
      by others that a right hemicolectomy provides the best outcome with respect to
      surgical procedure. Postoperative irradiation appears to provide a benefit for
      both local control and overall survival.

PMID- 9290694
TI  - Protection of marginal mandibular nerve during neck dissection.

PMID- 9290695
TI  - Update on active specific immunotherapy with melanoma vaccines.
AB  - Although a randomized clinical trial has yet to show a statistically significant
      improvement in the survival of patients receiving vaccine therapy for malignant
      melanoma, several studies have shown enhanced survival of patients developing an
      immune response to a melanoma vaccine. The knowledge and techniques of modern
      molecular biology and immunology suggest multiple strategies to augment this
      response. The challenge of immunotherapy research is to determine which
      combination of approaches leads to a favorable clinical response and how to
      monitor that response effectively. This review identifies components of a
      successful vaccine, discusses new ways to modulate and stimulate the immune
      system, and summarizes some of the more interesting clinical trials of melanoma
      vaccine immunotherapy.

PMID- 9290696
TI  - Interstitial implantation techniques in prostate cancer.
AB  - Brachytherapy is a radiotherapeutic technique that allows the physician to
      implant radioactive isotopes into a body cavity or directly into tissue.
      Different radioisotopes have unique characteristics that the brachytherapist may
      utilize for a particular situation. The use of brachytherapy is part of standard
      radiation oncology practice in gynecological and head and neck cancer management.
      The prostate is approachable for interstitial implantation due to its close
      proximity to the perineum. Over 20 years ago, primitive methods of brachytherapy
      were utilized in the treatment of prostate cancer. However, poor results due to
      inconsistency in achieving adequate coverage of the entire prostate and poor
      patient selection caused this treatment modality to fall out of favor.
      Technological advances over the last decade have restored attention to
      brachytherapy for prostate cancer. Particularly important has been the
      development of transrectal ultrasound, new radioisotopes such as palladium-103,
      computer tomography, computerized dosimetry systems, and earlier diagnosis.
      Modern interstitial implantation utilizing transperineal template and transrectal
      ultrasound guidance has resulted in improved consistency in radiation dose
      delivery to the entire prostate. Early results are encouraging in terms of the
      relatively low morbidity of the procedure, improved local control rates, and
      biochemical progression free survival. This has resulted in an outpatient
      treatment that has high patient acceptance.

PMID- 9290697
TI  - Frequent inactivation of the p16 gene in human pituitary tumors by gene
      methylation.
AB  - Rodent models of pituitary tumorigenesis have implicated the retinoblastoma (Rb)
      pathway in the development of pituitary tumors. Previously, we reported that loss
      of p16 expression rather than loss of Rb occurs in most human pituitary adenomas.
      This alteration in these tumors is not associated with p16 mutation or frequent
      homozygous p16 gene loss. Our laboratory has now demonstrated that in most human
      pituitary tumors, the 5' CpG island of the p16 gene is extensively methylated.
      The high frequency of p16 gene methylation in human pituitary tumors suggests
      that this alteration is an early and perhaps required event in pituitary cell
      transformation.

PMID- 9290698
TI  - Matrilysin gene expression in sporadic and familial colorectal adenomas.
AB  - We examined the expression of matrilysin mRNA in sporadic and hereditary
      colorectal adenomas to clarify the role of matrilysin in tumorigenesis.
      Matrilysin mRNA was not detected in normal colorectal mucosa from patients with
      either sporadic or familial adenomas. Matrilysin mRNA expression in sporadic
      adenomas correlated with the degree of dysplasia and the size of the mass,
      whereas most of the adenomas in patients with familial adenomatous polyposis coli
      expressed matrilysin mRNA irrespective of adenoma size or degree of dysplasia.
      Because matrilysin is more likely to be expressed in adenomas with a potential
      for malignancy, this enzyme may play a role in the malignant conversion of
      colorectal adenomas.

PMID- 9290699
TI  - Polymerase chain reaction-single-strand conformation polymorphism analysis for
      the VHL gene in chemically induced kidney tumors of rats using intron-derived
      primers.
AB  - von Hippel-Lindau (VHL) gene mutations occur throughout three exons including the
      exon-intron boundaries in human VHL disease-associated and sporadic renal cell
      carcinomas. To explore the possible role of the VHL gene in chemically induced
      rat kidney tumors originating from various cell types, more than 150 bp of
      Fischer 344 and Noble rat VHL intron sequences flanking the three exons was
      determined by dideoxy sequencing. Five primer sets were selected for polymerase
      chain reaction amplification of the coding regions of rat VHL exons 1-3 and the
      exon-intron boundaries. Tissues from 10 renal eosinophilic epithelial tumors
      induced by N-nitrosoethyl(2-hydroxyethyl)amine, 10 nephroblastomas induced by N
      nitroso-N-ethylurea, and seven renal mesenchymal tumors induced by N
      nitrosomethyl(methoxymethyl)amine were examined for VHL mutations by polymerase
      chain reaction-single-strand conformation polymorphism analysis. No mutation was
      detected in any tumor type, indicating that VHL mutations are not involved in the
      pathogenesis of rat kidney tumors arising from the distal region of the renal
      tubules, the metanephric blastema, or stromal tissues of the cortex.

PMID- 9290700
TI  - Accelerated onset of uterine tumors in transgenic mice with aberrant expression
      of the estrogen receptor after neonatal exposure to diethylstilbestrol.
AB  - The role of estrogen and the estrogen receptor (ER) in the induction and
      promotion of tumors was investigated by using transgenic MT-mER mice, which
      overexpress the ER. It was hypothesized that because of this abnormal expression
      of the ER, the reproductive-tract tissues of the MT-mER mice may be more
      susceptible to tumors after neonatal exposure to the potent synthetic estrogen
      diethylstilbestrol (DES). Normally non-estrogen responsive tissues that may have
      expressed ER as a result of the transgene were also studied for DES-induced
      tumors. Wild-type and MT-mER littermates were treated with 2 micrograms/pup/d DES
      1-5 d after birth and then killed at 4, 8, 12, and 18 mo of age. The DES-treated
      MT-mER mice demonstrated a significantly higher incidence of uterine
      adenocarcinoma at 8 mo (73%) than the DES-treated wild-type mice (46%). The
      tumors of the MT-mER mice were often more aggressive than those in the wild-type
      animals. These tumors were also preceeded at 4 mo by a significantly higher
      incidence of the preneoplastic lesion atypical hyperplasia in the MT-mER mice
      (26% compared with 0% in the wild-type mice). Other DES-induced abnormalities
      were observed at equal rates in the wild-type and MT-mER mice. Although no tumors
      were observed in untreated wild-type females, a single untreated MT-mER female
      had uterine adenocarcinoma at 18 mo. These data indicate that the level of ER
      present in a tissue may also be a determining factor in development of estrogen
      responsive tumors.

PMID- 9290701
TI  - Screening the p53 status of human cell lines using a yeast functional assay.
AB  - We have screened the p53 status of 156 human cell lines, including 142 tumor cell
      lines from 27 different tumor types and 14 cell lines from normal tissues by
      using functional analysis of separated alleles in yeast. This assay enables us to
      score wild-type p53 expression on the basis of the ability of expressed p53 to
      transactivate the reporter gene HIS3 via the p53-responsive GAL1 promotor in
      Saccharomyces cerevisiae. Of 142 tumor cell lines, at least 104 lines (73.2%)
      were found to express the mutated p53 gene: 94 lines (66.2%) were mutated in both
      alleles, three lines (2.1%) were heterozygous, and no p53 cDNA was amplified from
      seven lines (4.9%). Of the 14 cell lines originating from normal tissues, all the
      transformed or immortalized cell lines expressed mutant p53 only. Yeast cells
      expressing mutant p53 derived from 94 cell lines were analyzed for temperature
      sensitive growth. p53 cDNA from eight cell lines showed p53-dependent temperature
      sensitive growth, growing at 30 degrees C but not at 37 degrees C. Four
      temperature-sensitive p53 mutations were isolated: CAT-->CGT at codon 214
      (H214R), TAC-->TGC at codon 234 (Y234C), GTG-->ATG at codon 272 (V272M), and GAG-
      >AAG (E285K). Functionally wild-type p53 was detected in 38 tumor cell lines
      (26.8%) and all of the diploid fibroblasts at early and late population doubling
      levels. These results strongly support the previous findings that p53
      inactivation is one of the most frequent genetic events that occurs during
      carcinogenesis and immortalization.

PMID- 9290702
TI  - Integrity of the 1,25-dihydroxyvitamin D3 receptor in bone, lung, and other
      cancers.
AB  - Differentiation and proliferation can be regulated in diverse cell types by 1,25
      dihydroxyvitamin D3. These effects derive from modulation of gene expression
      mediated by the interaction of 1,25-dihydroxyvitamin D3 with the vitamin D
      receptor (VDR). The VDR is one of the nuclear hormone receptors. Because these
      transcription factors play a key role in growth control, some nuclear hormone
      receptors, such as the retinoic acid receptor alpha, can be disrupted in cancer.
      With these alterations in mind, we looked for alterations of the VDR gene in a
      variety of cancers, including 68 osteosarcomas, 23 other sarcomas, 34 non-small
      cell lung cancers, and 44 cell lines representing many tumor types. Gross
      integrity of the VDR gene was examined on Southern blots probed with the coding
      region of the VDR cDNA. The presence of point mutations targeting VDR exons 2-7
      was assessed by polymerase chain reaction-single-strand conformation polymorphism
      analysis and direct DNA sequencing. Two alterations were detected; direct DNA
      sequencing of these samples revealed one silent mutation in codon 79 and a base
      change in intron 3. These results suggest that mutations and rearrangement of the
      VDR do not play a role in the cancers studied.

PMID- 9290703
TI  - Fibroblast-directed expression and localization of 92-kDa type IV collagenase
      along the tumor-stroma interface in an in vitro three-dimensional model of human
      squamous cell carcinoma.
AB  - The malignant dissemination of tumors has been shown to require expression of one
      or more members of the matrix metalloprotease (MMP) enzyme family, whose function
      is to catalyze degradation of extracellular matrix proteins. In human squamous
      cell carcinoma (SCC) of the skin, expression of the MMP 92-kDa type IV
      collagenase (MMP-9), was previously shown to localize to malignant keratinocytes
      residing along the tumor/stromal interface. The purpose of the study presented
      here was to determine whether this localized expression pattern is due to
      interactions between SCC cells and adjacent stromal fibroblasts. To examine this
      question, SCC cells were grown as organotypic skin cultures, an in vitro three
      dimensional model of reconstructed human epidermis in which keratinocytes are
      grown on a type 1 collagen gel embedded with human dermal fibroblasts. In this
      study, MMP-9 expression was compared in organotypic cultures (constructed with
      SCC cells or the non-tumorigenic keratinocyte cell line HaCaT), in which human
      dermal fibroblasts were either included or excluded from the underlying stromal
      layer. In the absence of fibroblasts, expression of MMP-9 was slightly higher in
      SCC than HaCaT cultures. In cultures constructed with fibroblasts, however,
      induction of MMP-9 mRNA was observed in SCC but not HaCaT cultures. This
      induction of MMP-9 mRNA was accompanied by high levels of MMP-9 protein
      expression along the SCC/stromal interface. These data provide strong evidence
      that interactions between malignant keratinocytes and adjacent stromal
      fibroblasts are critical in directing expression of MMP-9 to the tumor-stroma
      interface in human SCC tumors.

PMID- 9290704
TI  - Localization of a putative liver tumor suppressor locus to a 950-kb region of
      human 11p11.2-p12 using rat liver tumor microcell hybrid cell lines.
AB  - We previously demonstrated that a locus (or loci) linked to the D11S436 marker,
      which is within the approximately 6-Mb cen-p12 region of human chromosome 11,
      suppresses the tumorigenic potential of some rat liver epithelial tumor microcell
      hybrid (MCH) cell lines. To more precisely map this putative liver tumor
      suppressor locus, we examined 25 loci from human chromosome 11 in suppressed MCH
      cell lines. Detailed analysis of these markers revealed a minimal area of overlap
      among the suppressed MCH cell lines corresponding to the chromosomal region
      bounded by (but not including) microsatellite markers D11S1319 and D11S1958E and
      containing microsatellite markers D11S436, D11S554, and D11S1344. Direct
      examination of the kang ai 1 (KA/1) prostatic adenocarcinoma metastasis
      suppressor gene (which is closely linked to D11S1344) produced evidence
      suggesting that this locus was not responsible for tumor suppression in this
      model system. In addition, our data strongly suggested that the putative liver
      tumor suppressor locus was distinct from other known 11p tumor suppressor loci,
      including the multiple exotoses 2 locus (at 11p11.2-p12), Wilms' tumor 1 locus
      (at 11p13), and Wilms' tumor 2 locus (at 11p15.5). The results of this study
      significantly narrowed the chromosomal location of the putative liver tumor
      suppressor locus to a region of human 11p11.2-p12 that is approximately 950 kb.
      This advance forms the basis for positional cloning of candidate genes from this
      region and, in addition, identified a number of chromosomal markers that will be
      useful for determining the involvement of this locus in the pathogenesis of human
      liver cancer.

PMID- 9290705
TI  - Analysis of genetic alterations in uterine leiomyomas and leiomyosarcomas by
      comparative genomic hybridization.
AB  - Uterine leiomyomas are the most prevalent tumor type in women of reproductive age
      and are the most common reason for hysterectomies. Although uterine leiomyomas
      are considered to be benign, they are a major public health concern for women. In
      contrast, leiomyosarcomas are rare but highly malignant uterine tumors. They may
      arise in uteri with preexisting leiomyomas and histologically sometimes resemble
      leiomyomas, thus causing controversy about whether leiomyosarcomas arise within
      leiomyomas. In this study, we used comparative genomic hybridization (CGH) to
      identify genetic alterations unique to each tumor type and alterations that are
      common between the two tumors. We analyzed 14 cases of uterine leiomyomas and
      eight cases of uterine leiomyosarcomas. Only two of the 14 leiomyomas exhibited
      genetic alterations, and those were restricted to gains on chromosomes 14 and 19
      and losses on chromosomes 1 and 4. In addition, 68 leiomyomas were examined for
      loss of heterozygosity on chromosomes 1 and 4, and only three tumors exhibited
      any losses. In contrast, all eight leiomyosarcomas showed gains and losses of DNA
      by CGH, and in many cases multiple changes were observed. The most commonly
      observed genetic aberration, occurring in five tumors, was gains on both arms of
      chromosome 1, suggesting that this chromosome contains loci involved in the
      development of leiomyosarcoma. Our results do not provide evidence for the
      progression from benign leiomyoma to malignant leiomyosarcoma. Moreover, the
      large number of random chromosomal alterations in the leiomyosarcomas suggests
      that increased genetic instability plays a role in the formation of these tumors.

PMID- 9290706
TI  - Management of head-injured patients in the emergency department: a practical
      protocol.
AB  - BACKGROUND: The management of head-injured patients admitted to emergency
      departments is not standardized. METHODS: The authors performed a retrospective
      analysis of 10,000 head-injured patients admitted to the Emergency Department of
      our hospital in a 21-month period and, on the basis of a statistical correlation
      between each clinical parameter (symptoms and signs upon arrival at the hospital
      or risk factors) and the presence of intracranial lesions, they propose a
      practical protocol in an attempt to avoid the overuse or radiologic examinations
      and yet identify patients with possible life-threatening complications. RESULTS:
      On the basis of this correlation the patients have been divided into four groups.
      In the first group (called group alpha) are patients with: no history of loss of
      consciousness, no vomiting or amnesia, a normal neurologic examination, and
      minimal if any subgaleal swelling. They can be released into the care of
      relatives who are given a special instruction sheet (X rays unnecessary). No
      patient in group alpha had complications of any kind. The second group (group
      beta) is made up of patients with at least one of the following features:
      transient loss of consciousness, post-traumatic amnesia, a single episode of
      vomiting or significant subgaleal swelling. They undergo a computed tomography
      (CT) scan and if this is normal, only a short period of observation is needed. If
      CT scan is not available, the skull is X rayed and, if this X ray is negative,
      the patient is sent home with the warning sheet after an observation period. If a
      fracture is found, CT scan should be performed promptly. No patient in group beta
      with normal skull X rays developed intracranial lesions. The third group (group
      gamma) contains patients with at least one of the following symptoms: impaired
      consciousness, repeated episodes of vomiting, neurologic deficits, otorrhagia,
      otorrhea, rhinorrea, signs of basal skull fracture, seizures, penetrating or
      perforating wounds, lack of cooperation for varying reasons, patients who have
      undergone previous intracranial operations or been affected by coagulopathy or
      submitted to anticoagulant therapy, and finally, epileptic or alcoholic patients.
      They receive a CT scan immediately and, if necessary, again prior to discharge.
      Six patients in group gamma with GCS = 15 upon admission were operated on for
      intracranial hematoma. The fourth group (group delta) is composed of comatose
      patients. Immediately following resuscitation maneuvers and prior to any surgical
      intervention, they undergo a CT scan. A linear association between the severity
      groups and the presence of intracranial lesions has been demonstrated.
      CONCLUSIONS: The present protocol stresses the importance of the patient's
      clinical and anamnestic evaluation upon arrival in the Emergency Department,
      especially in minor head injuries.

PMID- 9290707
TI  - Chronic subdural hematoma: surgical treatment and outcome in 104 patients.
AB  - BACKGROUND: The common occurrence of chronic subdural hematoma (CSDH) in older
      patients raises some diagnostic and therapeutic difficulties. Despite general
      agreement about the indication of operation, the extent of surgery is still
      discussed controversially. We have, therefore, reviewed operative findings and
      outcome in 104 patients with CSDH. METHODS: Retrospective analysis was performed
      by differentiating age < or = 60 years (n = 28) versus age > 60 years (n = 76)
      and burr hole craniostomy with a size range from 12-30 mm (n = 94) versus larger
      craniotomy (n = 10). All patients received closed-system drainage of the subdural
      space for 2-4 days. RESULTS: Four patients older than 60 years died within 30
      days after surgery, two in each operative group. Excluding these postoperative
      deaths, 17 out of 92 patients (18.5%) after burr hole trepanation and one out of
      eight patients (12.5%) after craniotomy required reoperation due to rebleeding (n
      = 6), residual subdural fluid (n = 4), and residual thick hematoma membranes (n =
      8). Eight patients, who had been initially treated by burr hole craniostomy
      despite preoperative detection of neomembranes by contrast-enhanced computed
      tomography (CT) or magnetic resonance imaging (MRI), recovered without further
      intervention. Clinical outcome was good in both operative groups. The percentage
      of patients without or with only mild neurologic deficits at the time of
      discharge from the hospital was 72.3% in the burr hole and 70.0% in the
      craniotomy group, respectively. CONCLUSIONS: The clinical data of the present
      study suggest that burr hole craniostomy with closed-system drainage should be
      the method of choice for the initial treatment of CSDH, even in cases with
      preoperative detection of neomembranes. Craniotomy should be carried out only in
      patients with reaccumulating hematoma or residual hematoma membranes, which
      prevent reexpansion of the brain.

PMID- 9290708
TI  - Delayed extradural hematoma after mild head injury: report of three cases.
AB  - BACKGROUND: Extradural hematoma has been classically considered to be an acute
      complication of head injury whose maximum development takes place in the minutes
      following trauma. Delayed extradural hematoma (DEH) is defined on the basis of an
      exclusively radiologic criterion: epidural hematoma that is not present in the
      first neuroradiologic examination made after trauma but that appears in
      sequential neuroradiologic examinations during patient evolution. This is an
      infrequent complication that usually appears in hypotensive multiple trauma
      patients or is related to severe head injury with other intracranial lesions.
      CASE DESCRIPTION: We present three cases of DEH after mild head injury (GCS > 12)
      without associated intracranial or traumatic systemic lesions. Therefore, those
      usually considered to be "protective mechanisms" responsible for delayed
      development of an extradural hematoma were absent in our three patients.
      Diagnosis was attained by means of repetition of cranial computed tomography (CT)
      scan after neurologic impairment was noted. Surgical evacuation of DEH was
      immediately performed after diagnosis. Postoperative outcome was favorable in two
      patients who suffered DEH in the supratentorial compartment. One patient who
      presented a posterior fossa DEH died 3 days after surgery. CONCLUSIONS: Early
      diagnosis and immediate treatment have proved to be essential for improving the
      prognosis of patients affected by DEH. Hospital admission under neurologic
      observation is recommended for patients who have sustained mild head injury
      associated with those factors that are related to the development of DEH,
      including GCS score under 15 or the detection of a skull fracture. Normality of a
      CT scan does not rule out subsequent appearance of delayed traumatic lesions.

PMID- 9290709
TI  - The location of the intervertebral lumbar disc on the posterior aspect of the
      spine.
AB  - BACKGROUND: Epidural fibrosis or scar formation is considered one cause of failed
      lumbar discectomy. Avoidance of unnecessary bony resection of the lamina may
      prevent or decrease postoperative scar formation. The knowledge of the precise
      location of the projection of the lumbar disc may also facilitate surgery and
      decrease patient morbidity. No studies exist regarding the projection of the
      lumbar disc on the posterior aspect of the lumbar spine. METHODS: Thirty-six
      whole lumbar spine specimens from L1 to L5 (180 lumbar vertebrae) and sacra were
      used for this study. Anatomic evaluation included the distance between the
      superior border of the vertebral body (inferior border of the intervertebral
      disc) and the superiormost margin of the lumbar lamina, and the distance between
      the inferior border of the vertebral body (superior border of the intervertebral
      disc) and the inferiormost margin of the lumbar lamina. The width of the
      interlaminar space was also measured. RESULTS: The data showed that the level of
      the superior margin of the lamina was consistently inferior to the superior
      border of the corresponding vertebral body from L1 to S1. This distance for both
      sexes ranged from 10 to 11 mm for L1-L5 and 14 mm for S1. The level of the
      inferior margin of the lamina varied from 3 mm inferior to 9 mm superior to the
      inferior border of the corresponding vertebral body for L1-L5. The width of the
      interlaminar space averaged from 16.8 mm for L1 to 31.0 mm for L5. CONCLUSIONS:
      This study suggests that the superior margin of the lamina represents a
      consistent, useful landmark in determining the location of the lumbar disc on the
      posterior aspect of the spine. The relationship between the inferior margins of
      the lamina and the vertebral body is not consistent.

PMID- 9290710
TI  - Evaluation of prognostic factors following expansive laminoplasty for cervical
      spinal stenotic myelopathy.
AB  - BACKGROUND: Expansive laminoplasty of several types has been proposed for
      patients with cervical multisegmental stenotic myelopathy to reduce
      postlaminectomy complications. Its effectiveness has not been fully explored by
      evaluating long-term results and magnetic resonance imaging (MRI) findings before
      and after surgery. METHODS: We conducted a 5-year follow-up study of 22 patients
      with cervical spondylotic myelopathy and/or ossification of the posterior
      longitudinal ligament surgically treated with expansive laminoplasty. The
      operative results were examined using the Japanese Orthopedic Association (JOA)
      disability scale, with reference to the findings of MRI, computed tomography, and
      radiography. RESULTS: Postoperative improvement was observed in 18 (81.8%) of the
      22 patients. In 11 patients the percentage recovery of the JOA score was higher
      than 50% (average: 83.1%), while in the remaining 11 patients it was lower than
      50% (average: 20.1%). Factors contributing to incomplete recovery appear to be
      related mainly to cord degeneration with atrophy (depicted as a T2-high intensity
      area) and to specific factors such as long symptom duration, age higher than 70
      years, deterioration due to trauma, severe cord compression, radiculopathy, and
      kyphotic cervical curvature. CONCLUSIONS: In cervical myelopathy, patients with
      multisegmental stenosis, expansive laminoplasty can be expected to provide a
      favorable outcome by providing sufficient cord decompression and stabilization of
      the cervical spine, when the stenotic cervical canal is enlarged to the normal
      range (over 12 mm residual anteroposterior diameter and 200 mm2 residual canal
      area). The efficacy can be restricted by various factors, especially irreparable
      cord degeneration.

PMID- 9290712
TI  - Cerebral meningioangiomatosis: case report.
AB  - We discuss the clinical, neuroradiologic and histopathologic features of a case
      not apparently associated with neurofibromatosis (type 2), reviewing the relevant
      literature.

PMID- 9290711
TI  - Experimental syringomyelia: late ultrastructural changes of spinal cord tissue
      and magnetic resonance imaging evaluation.
AB  - BACKGROUND: In human hydrosyringomyelia and in the late stage of experimental
      syringomyelia, the spinal cord tissue adjacent to the syrinx is exposed to a
      similar pathophysiologic condition. We investigated the ultrastructural changes
      in the late stages of kaolin-induced syringomyelia, and in addition, we presented
      magnetic resonance imaging (MRI) findings of the cervicomedullary junction and
      syrinx, and the nature of edema in the spinal cord of this experimental model.
      METHODS: Syringomyelia was induced in rabbits by intracisternal injection of
      kaolin. MRI was performed at 6 weeks, and 6 and 12 months following injection,
      and the animals were killed by transcardial perfusion of formaldehyde solution
      and examined by transmission electron microscopy. Evans blue was injected
      intravenously in six rabbits, 6 weeks and 12 months following kaolin injection
      and was examined by confocal laser scanning microscopy. RESULTS: MRI showed that
      the syrinx communicated with the fourth ventricle in most animals. Demyelination
      of varying degrees and slight edematous change were seen in the perisyrinx white
      matter. No extravasation of Evans blue was seen by confocal microscopy. Abundant
      astrocytic proliferation with a large number of glial filaments was seen at the
      margin of the syrinx and between the axons in the perisyringeal region. The
      perivascular space enlargement occurred in both the gray and white matter. The
      endothelial junctions appeared intact. Regenerating axons and remyelination by
      oligodendrocytes were seen occasionally. CONCLUSIONS: The MRI confirmed the
      communication between the fourth ventricle and the syrinx. The ultrastructural
      changes were almost identical to those of the early stage syrinx, but the
      astrocytic proliferation was more severe, and the edema was less in the late
      stage. The perisyrinx edema appeared to be of the interstitial type, as in
      hydrocephalus. Axonal degeneration and demyelination continued with abortive
      attempt at regeneration and remyelination in the less edematous late stage, which
      might be the cellular basis for the persistence or worsening of clinical symptoms
      and signs in the chronic stage of syringomyelia even after surgical treatment.

PMID- 9290713
TI  - Isolated deep cerebral venous thrombosis treated by direct endovascular
      thrombolysis.
AB  - BACKGROUND: Isolated thrombosis of the deep cerebral venous system is very rare
      and is associated with a poor prognosis. Antithrombin III (AT III) deficiency is
      a disorder of hypercoagulability associated with deep venous thrombosis and
      recurrent pulmonary emboli. We report a case of an 18-year-old man who presented
      with spontaneous thrombosis of the deep cerebral veins and straight dural sinus
      as the initial presentation of a previously undiagnosed AT III deficiency.
      METHODS: The patient was managed using direct endovascular infusion of the
      fibrinolytic agent urokinase followed by intravenous heparin. RESULTS: The
      technique was successful in establishing patency of the deep cerebral venous
      system. The patient experienced a good clinical outcome. CONCLUSIONS: Direct
      endovascular thrombolysis is a potentially effective management strategy for
      isolated thrombosis of the deep cerebral venous system.

PMID- 9290714
TI  - Computerized tomography and magnetic resonance guided stereotactic brain biopsy
      in nonimmunocompromised and AIDS patients.
AB  - BACKGROUND: The utility of stereotactic brain biopsy (SBB) in AIDS patients still
      remains controversial. The authors investigated SBB-related diagnostic accuracy,
      complications, and postoperative sequelae in nonimmunocompromised (NIC) patients
      and AIDS patients. The role of bioptic yield in treatment planning was also
      studied in AIDS patients. METHODS: From 1990-95, 200 computerized tomography (CT)
      or magnetic resonance imaging (MRI)-guided SBBs were performed in our Department;
      172 bioptic procedures were performed in NIC patients (169), and 28 SBBs in AIDS
      patients (27). The statistical significance was evaluated using the Fisher exact
      t-test. RESULTS: SBB accuracy was very high in both NIC (94.8%) and AIDS (92.9%)
      patients. Statistical analysis indicated nonsignificant (NS) differences between
      the two study groups (P > 0.05). Diagnostic yield resulted higher in contrast
      enhancing (CE) brain lesions (98.6% in NIC and 95.0% in AIDS patients; P > 0.05;
      NS), than in non-CE lesions (74.1% in NIC and 87.5% in AIDS patients; P > 0.05;
      NS). The overall complication rate was similar in both groups (17.2% in NIC and
      14.8% in AIDS patients, P > 0.05, NS). The most frequent complication was
      hemorrhage, with statistically negligible differences between the two study
      groups (P > 0.05). The frequency of complications involving minor/major morbidity
      or mortality was very low in NIC (5.9%, 0.6%, and 2.4%, respectively), and in
      AIDS (3.7%, 7.4%, and 0.0%, respectively) patients. Regarding the therapeutic
      impact of bioptic diagnosis for neuro-AIDS patients, the preoperative treatment
      attitude was modified in 23/27 cases (85.2%), and the empiric anti-toxoplasmosis
      regimen was changed or withdrawn in 17/21 patients (81.0%). CONCLUSION: Our
      experience demonstrated SBB to be an accurate, manageable, and reasonably safe
      diagnostic tool in both NIC and AIDS patients. These results suggest also that
      timely SBB indication in selected AIDS patients, reaching an early diagnosis, may
      on one side prevent unnecessary and potentially toxic empiric therapeutic
      regimens, and on the other address the appropriate treatment, thereby improving
      length and quality of life in such patients.

PMID- 9290715
TI  - Diagnostic and staged stereotactic aspiration of multiple bihemispheric pyogenic
      brain abscesses.
AB  - BACKGROUND: Empiric antibiotic therapy for multiple brain abscesses is not
      advised, as biopsy to rule out other causes and material for cultures can be
      obtained with minimal morbidity using computed tomography (CT)-guided stereotaxy.
      METHODS: We report a good outcome following treatment of this 60-year-old
      nonimmunocompromised patient with six pyogenic cerebral abscesses. CT-guided
      stereotactic aspiration of two abscesses were done on the first occasion and
      appropriate antibiotics were administered. Serial CT scans were done and the
      abscesses that recollected or enlarged were again aspirated. RESULTS: Group A
      beta hemolytic streptococci were grown from the pus. Two abscesses recollected
      and one enlarged during antibiotic therapy. These were aspirated on the second
      and third occasions, 1 week and 2 weeks after the first procedure. The abscess
      less than 3 cm resolved with antibiotics alone. Intravenous crystalline
      penicillin, chloroamphenicol, and metronidazole were given for 2 weeks followed
      by oral ampicillin and cotrimoxazole for 10 weeks. There was no morbidity related
      to the multiple procedures and the patient had a good outcome at the end of 16
      weeks. CONCLUSIONS: CT-guided stereotactic aspiration of multiple brain abscesses
      is known to have a low morbidity and mortality. We highlight the additional
      option of multiple, staged aspirations for those abscesses not readily responding
      to antibiotic therapy.

PMID- 9290717
TI  - Intrathecal granuloma after implantation of a morphine pump: case report and
      review of the literature.
AB  - BACKGROUND: Intrathecal morphine pumps are being increasingly used in patients
      with benign pain who have a longer life expectancy than cancer patients. Newer
      complications may be encountered. CLINICAL PRESENTATION: We report a complication
      that occurred in a 48-year-old woman who presented with intractable lower back
      pain 18 months after morphine pump implantation. Magnetic resonance imaging of
      the lumbosacral spine revealed an intrathecal mass around the catheter. At
      surgery, an inflammatory mass was found without any evidence of neoplasia or
      infection. This is a very unusual complication of intrathecal morphine pumps.
      (Related animal and human studies are reviewed in this article.) CONCLUSION: Long
      term use of implantable pumps may carry increased risks that are not observed
      during the short-term experience of cancer patients. Reimaging is important in
      evaluating patients who have developed uncontrollable pain and new neurologic
      findings.

PMID- 9290716
TI  - Brain abscess in renal transplant recipients: report of three cases.
AB  - BACKGROUND: Neurologic complications occur in about 30% of renal transplant
      patients, infections being the most common. We encountered three such patients
      and present our experience in the management of such cases. CLINICAL MATERIAL:
      Three cases of brain abscess in renal transplant recipients are reported. These
      patients presented from 9-60 months after the transplant. One patient had a
      pyogenic abscess; in the second the organism identified was Nocardia asteroides;
      in the third, a fungal infection was responsible. In two patients excision of the
      abscess was done, while in one repeated aspirations with intracavitary
      antibiotics were used. All received systemic antimicrobial therapy. CONCLUSIONS:
      Central nervous system (CNS) complications, specifically infections, are quite
      common in renal transplant recipients, but reports of brain abscesses in these
      patients are very rare. The treatment options for such patients are discussed.

PMID- 9290718
TI  - Prophylaxis for anaphylactoid reactions in high risk patients receiving
      radiopaque contrast media.

PMID- 9290719
TI  - An innovative approach for cranioplasty using hydroxyapatite cement.

PMID- 9290720
TI  - The T2 hypointense brain abscess capsule: is it pathognomonic?

PMID- 9290721
TI  - Philosophy of practice development.

PMID- 9290722
TI  - Neurosurgery in Vietnam.
AB  - BACKGROUND: The development and current state of Vietnamese neurosurgery is
      presented, in order to highlight the difficulties faced by neurosurgeons in
      Vietnam and other developing countries. METHODS: Information has been collected
      personally by the authors in Vietnam. RESULTS: The conditions of neurosurgery
      endured by our neurosurgical colleagues in Vietnam are far inferior to those in
      the developed world, particularly in terms of training, educational aids,
      investigative and operating room equipment, and postoperative and rehabilitative
      care. CONCLUSIONS: The recent formation of the Neurosurgical Society of Vietnam
      will help to improve these conditions, but help and encouragement from
      neurosurgeons in the developed world will also be of much value. The instigation
      of preventive strategies will likely make a significant impact on the health
      costs of neurotrauma in Vietnam.

PMID- 9290723
TI  - A profession in retreat.

PMID- 9290724
TI  - A profession in retreat.

PMID- 9290725
TI  - Pearl jam.

PMID- 9290726
TI  - Contributions of cellular and humoral immunity to arteriopathic lesions in
      transplanted mouse hearts.

PMID- 9290727
TI  - Posttransplant antibody response and chronic rejection.

PMID- 9290728
TI  - Knockout models of chronic cardiac rejection and graft arteriosclerosis: intimal
      thickening develops independent of Th1 and Th2 cytokines.

PMID- 9290729
TI  - Functional Fas and Fas-ligand activities in activated T cells of kidney
      transplant recipients.

PMID- 9290730
TI  - Intragraft cytokine and growth factor mRNA expression in relation to graft
      vascular disease after heart transplantation.

PMID- 9290732
TI  - Graft atherosclerosis and chronic rejection in the kidney.

PMID- 9290731
TI  - Is chronic rejection of liver transplants different from graft arteriosclerosis
      of kidney and heart transplants?

PMID- 9290733
TI  - Graft arteriosclerosis: molecular features of macrophage activation.

PMID- 9290735
TI  - Chronic rejection in rhesus monkey kidney allografts.

PMID- 9290734
TI  - Nonspecific immune reactivity of peripheral blood mononuclear cells is related to
      graft vascular disease.

PMID- 9290736
TI  - Role of growth factors in graft vessel disease.

PMID- 9290737
TI  - Temporal relationship between insulin-like growth factor-I and platelet-derived
      growth factor-BB expression in the rat aorta allograft in the early phase
      following transplantation.

PMID- 9290738
TI  - Immune and nonimmune clinical correlates of chronic renal allograft rejection.

PMID- 9290739
TI  - Ischemia induced upregulation of growth factor expression in experimental
      transplant arteriosclerosis.

PMID- 9290740
TI  - Genes upregulated in ischemia-induced arteriosclerosis in rat aortic transplants.

PMID- 9290741
TI  - Progression of changes in arteries following cold storage preservation in UW and
      Collins solution in a syngeneic aortic transplant model.

PMID- 9290742
TI  - Effect of locally and systemically administered angiopeptin on growth factor
      expression in syngeneic deendothelialized heterotopic aorta grafts in the rat.

PMID- 9290743
TI  - Prevention of reperfusion-induced, free radical-mediated acute endothelial injury
      by superoxide dismutase as an effective tool to delay/prevent chronic renal
      allograft failure: a review.

PMID- 9290744
TI  - Inhibition of the inositol triphosphate receptor increases endotoxin-mediated
      nitric oxide synthesis in macrophages.

PMID- 9290745
TI  - Nitric oxide generation by nitric oxide synthase isoforms in transplanted
      vessels.

PMID- 9290746
TI  - Cardiac microvascular vasomotor response as a prognostic marker of left
      ventricular function in cardiac transplant recipients.

PMID- 9290747
TI  - Polymorphisms for angiotensin converting enzyme, angiotensinogen, nitric oxide
      synthase, and endothelin and their association with cardiac allograft
      vasculopathy in the first year posttransplant.

PMID- 9290748
TI  - Polymorphisms in genes of angiotensin converting enzyme, angiotensinogen, nitric
      oxide synthase, and endothelin and their association with cardiac allograft
      rejection.

PMID- 9290749
TI  - Endothelin-1 peptide expression in transplant coronary artery disease.

PMID- 9290750
TI  - Inducible nitric oxide synthase is upregulated in human transplant coronary
      artery disease.

PMID- 9290751
TI  - The role of inflammation in the development of allograft coronary disease.

PMID- 9290752
TI  - New insights and therapeutic strategies for postcardiac transplantation coronary
      artery disease.

PMID- 9290753
TI  - Treatment of kidney transplants with chronic rejection using angiotensin
      converting enzyme inhibitors.

PMID- 9290754
TI  - Do renal allograft function and histology at 6 months posttransplant predict
      graft function at 2 years?

PMID- 9290755
TI  - Cholesterol reduction in cyclosporine-treated renal transplant patients: effect
      on platelet-derived growth factor levels and platelet activation.

PMID- 9290756
TI  - Five-year follow-up of early post-renal transplantation cyclosporin withdrawal:
      do we benefit from a state of tolerance?

PMID- 9290757
TI  - The somatostatin analog octreotide as potential treatment for re-stenosis and
      chronic rejection.

PMID- 9290758
TI  - Extracellular matrix proteins and their interactions with the cellular repertoire
      of transplant recipients.

PMID- 9290759
TI  - The receptor for hyaluronan-mediated motility is expressed in human renal
      allografts and is correlated with Banff chronic rejection scores.

PMID- 9290760
TI  - Angiopeptin induces beneficial vascular remodeling after balloon injury.

PMID- 9290761
TI  - A new large animal heterotopic lung and bronchial allograft model for research in
      obliterative bronchiolitis.

PMID- 9290762
TI  - Progression of obliterative airway disease occurs despite the removal of immune
      reactivity by retransplantation.

PMID- 9290763
TI  - Infiltrating recipient mesenchymal cells form the obliterative airway disease
      lesion and dramatically remodel graft tissue in a model of chronic lung
      rejection.

PMID- 9290764
TI  - The immunolymphatic theory of chronic rejection.

PMID- 9290765
TI  - Bronchus-associated lymphoid tissue is targeted and damaged by recipient
      lymphocytes in long-term-surviving rat lung allograft.

PMID- 9290766
TI  - The DNA-binding activities of NF-AT and AP-1 can predict levels of
      immunosuppression of kidney transplant recipients.

PMID- 9290767
TI  - Preclinical models of chronic rejection: promises and pitfalls.

PMID- 9290769
TI  - Chronic rejection and graft arteriosclerosis: 4 years after the Alexis Carrel
      proposal on diagnostic criteria.

PMID- 9290768
TI  - Major histocompatibility complex class II antigen expression is suppressed by
      estradiol in cardiac allografts.

PMID- 9290770
TI  - Initial experience with living-related donor liver transplantation in Rabin
      Medical Center, Israel.

PMID- 9290771
TI  - Natural course of HCV viremia following liver transplantation and clinical course
      of reinfection.

PMID- 9290772
TI  - Impact of European donor hospital education on the knowledge and attitudes of
      health professionals toward organ donation in Israel.

PMID- 9290773
TI  - A 5-year experience in liver transplantation at Rabin Medical Center, Israel.

PMID- 9290774
TI  - Induction of mixed hematopoietic chimerism and specific transplantation tolerance
      to allogeneic and xenogeneic grafts by selective elimination of donor-reactive
      host cells following nonmyeloablative conditioning.

PMID- 9290775
TI  - Flow cytometry: is it the ultimate crossmatch technique in living donors?

PMID- 9290776
TI  - Immunization with WBC induces monocyte suppression activity in vitro.

PMID- 9290777
TI  - Xenotransplantation: a possible option for the future.

PMID- 9290778
TI  - Hepatitis GBV-C viremia in liver, heart, and bone marrow recipients.

PMID- 9290779
TI  - Role of percutaneous endoscopic gastrostomy in a malnourished patient awaiting
      lung transplant.

PMID- 9290780
TI  - Dose adjustment and cost of itraconazole prophylaxis in lung transplant
      recipients receiving cyclosporine and tacrolimus (FK 506).

PMID- 9290781
TI  - Alternative venous drainage for renal transplantation.

PMID- 9290782
TI  - Vasoactive effect of cyclosporine on the rat peribiliary capillary plexus:
      relationship with cholestasis and hyperbilirubinemia.

PMID- 9290783
TI  - Long-term follow-up of liver transplant patients in a nonliver transplantation
      center.

PMID- 9290784
TI  - Coated cyclosporine: a new method of lung targeting.

PMID- 9290785
TI  - Amphotericin B lipid complex in the treatment of invasive fungal infections in
      liver transplant patients.

PMID- 9290786
TI  - Etiological factors influencing the development of atrioventricular valve
      incompetence after heart transplantation.

PMID- 9290787
TI  - Natural course of de novo hepatitis B virus infection in liver transplant
      recipients.

PMID- 9290788
TI  - Should hepatitis B immunoglobulin therapy be discontinued after HBV reinfection
      following liver transplantation?

PMID- 9290789
TI  - Hepatitis-C-associated cryoglobulinemia after liver transplantation.

PMID- 9290790
TI  - Beneficial effect of lamivudine pre- and post-liver transplantation for hepatitis
      B infection.

PMID- 9290791
TI  - Ultraviolet B irradiation reduces the surface expression of conformationally
      correct class I and II histocompatibility antigens.

PMID- 9290792
TI  - Peripheral microchimerism in living donor kidney transplantation.

PMID- 9290793
TI  - Hepatitis HGV/GBV-C viremia in renal transplant recipients.

PMID- 9290794
TI  - Hepatitis C infection in renal transplant recipients in Israel.

PMID- 9290795
TI  - Reconstructed CT ureteropyelography for accurate diagnosis of urinary tract
      lesions after kidney transplantation.

PMID- 9290796
TI  - Immediate and late changes in renal endothelin-1 excretion after renal
      transplantation.

PMID- 9290797
TI  - Immunization with WBC suppresses T cells and NK activity in vitro.

PMID- 9290798
TI  - Beta-2 microglobulin in heart transplanted patients.

PMID- 9290800
TI  - Current issues in renal transplantation.

PMID- 9290799
TI  - Pretransplant crossmatching: an individualized process.

PMID- 9290801
TI  - Liver transplantation.

PMID- 9290802
TI  - Heart and lung transplantation.

PMID- 9290803
TI  - Small bowel and pancreas transplantation.

PMID- 9290804
TI  - Economics of transplantation in the 21st century: new scientific opportunities
      but greater economic problems.

PMID- 9290805
TI  - Purchasing transplants in the NHS.

PMID- 9290807
TI  - Xenotransplantation: ethical acceptability.

PMID- 9290806
TI  - Xenotransplantation--scientific aspects.

PMID- 9290808
TI  - Issues facing transplantation in the United Kingdom.

PMID- 9290810
TI  - The Bellagio Task Force report on transplantation, bodily integrity, and the
      International Traffic in Organs.

PMID- 9290809
TI  - Reversibility of tacrolimus-induced posttransplant diabetes: an illustrative case
      and review of the literature.

PMID- 9290812
TI  - Question regarding treatment of a cat with pancreatis.

PMID- 9290811
TI  - Another perspective on the case of digital infection in a bull.

PMID- 9290813
TI  - Strong opposition to the Yellowstone bison slaughter.

PMID- 9290814
TI  - Some views on the legitimacy of the myth of stolen-animal trafficking.

PMID- 9290815
TI  - Some views on the legitimacy of the myth of stolen-animal trafficking.

PMID- 9290816
TI  - What is your diagnosis? Comminution of T2 and luxation of T2 and T3.

PMID- 9290817
TI  - Intestinal metabolism of glutamine and potential use of glutamine as a
      therapeutic agent in diarrheic calves.

PMID- 9290818
TI  - Ethical standards and licensure.

PMID- 9290819
TI  - Review of the 1995 vesicular stomatitis outbreak in the western United States.

PMID- 9290820
TI  - Survey of humane organizations and slaughter plants regarding experiences with
      Vietnamese potbellied pigs.
AB  - OBJECTIVE: To determine to what extent humane organizations are receiving
      requests to take unwanted Vietnamese potbellied pigs and to determine whether
      owners of potbellied pigs are selling them for slaughter. DESIGN: Mail survey.
      SAMPLE POPULATION: 1,178 humane organizations in 7 states and 978 slaughter
      plants in 4 states. RESULTS: 802 (68%) humane organizations and 787 (81%)
      slaughter plants responded. Of the humane organizations that responded, 479 (60%)
      stated they were willing to accept potbellied pigs. Humane organizations received
      4,380 requests from owners to accept potbellied pigs during the study period and
      accepted 3,149 (72%) of these pigs. Six hundred fifteen (20%) of the potbellied
      pigs accepted were strays. Of the 437 humane organizations that provided reasons
      why owners relinquished their potbellied pigs, 255 (58%) reported larger than
      expected size, 148 (34%) reported zoning restrictions and 82 (19%) reported
      aggression. Of 485 slaughter plants that normally slaughtered hogs, 255 (53%) had
      received requests to slaughter potbellied pigs. These plants slaughtered 2,640
      and refused 1,407 potbellied pigs during the study period. CLINICAL IMPLICATIONS:
      Problems with larger than expected size, zoning restrictions, and aggressive
      behavior caused owners of Vietnamese potbellied pigs to relinquish their pets to
      humane organizations and slaughter plants.

PMID- 9290822
TI  - Scoliosis and associated cystic spinal cord lesion in a dog.
AB  - A 7-month-old female Mastiff was admitted for weakness in the hind limbs and an
      abnormal gait. There was an obvious scoliosis in the midlumbar region. Using
      electromyography, fibrillation potentials and positive sharp waves were found in
      the epaxial musculature of the vertebral column lateral to the spinous processes
      of Tl3-L4 on the right (convex) side of the body. On myelographic evaluation,
      contrast medium irregularly filled the subdural and epidural space of Tl1-L3. On
      surgical examination, the dog had a cystic lesion of the spinal cord that
      correlated with myelographic findings. This lesion was incised and drained. The
      scoliotic defect was surgically straightened, and the affected vertebrae were
      fused. Six months after surgery, the vertebral column continued to be straight
      and the paraparesis had resolved.

PMID- 9290823
TI  - Factor X deficiency in a cat.
AB  - Severe congenital deficiency of factor X was diagnosed in a 3-year-old castrated
      male domestic shorthair cat with clinical signs of generalized seizures and
      prolonged bleeding after venipuncture. Heritability of factor X deficiency was
      suspected because of a prolonged Russell's viper venom time in the dam and
      reductions in factor X activity in the dam and 1 sibling. To our knowledge,
      factor X deficiency in cats has not been reported previously. Definitive
      diagnosis for animals with clinical signs of coagulopathy may require repetition
      of coagulation screening tests using different assay methods or specific
      coagulation factor analyses.

PMID- 9290821
TI  - Diagnosis and surgical repair of partial atrioventricular septal defects in two
      dogs.
AB  - Partial atrioventricular (AV) septal defects consist of an ostium primum defect
      and malformation of the septal cusp of the mitral valve. A partial AV septal
      defect was diagnosed by means of echo-cardiography in 2 dogs. Transatrial septal
      blood flow was high enough in both dogs to warrant surgical correction. Defects
      were repaired through right fifth intercostal thoracotomies, with the aid of
      cardiopulmonary bypass. An incision was made in the right atrium to expose the AV
      septal defect, and the mitral valve was inspected through the septal defect. The
      cleft in the septal cusp of the mitral valve was repaired with mattress sutures
      of 6-0 polypropylene. The septal defect was closed with autogenous pericardium
      harvested from the right aspect of the pericardial sac. Both dogs survived
      surgery and were alive 15 and 42 months, respectively, after surgery, however, 1
      dog developed progressive mitral regurgitation after surgery. Partial AV septal
      defects can be successfully repaired in dogs. Long-term prognosis probably
      depends on the adequacy of the mitral valve repair.

PMID- 9290825
TI  - Persistent penile prolapse associated with acute blood loss and acepromazine
      maleate administration in a horse.
AB  - Prolonged penile prolapse in horses has been reported in association with
      administration of phenothiazine tranquilizers, trauma, neuropathies, severe
      general debilitation or exhaustion, starvation, rabies, herpes myeloencephalitis,
      equine infectious anemia, and purpura hemorrhagica. A 5-year-old gelding was
      admitted for treatment of prolonged penile prolapse of 12 days' duration that
      developed after acepromazine maleate was administered to allow examination of a
      laceration that had resulted in severe blood loss. The horse was sedated, and the
      penis was replaced in the preputial cavity by use of a combination of massage and
      bandaging. Treatment was successful, and recovery was complete.

PMID- 9290824
TI  - Aseptic loosening of the femoral implant after cemented total hip arthroplasty in
      dogs: 11 cases in 10 dogs (1991-1995).
AB  - Aseptic loosening of the femoral implant (ALFI) was diagnosed in 10 dogs that had
      undergone cemented total hip arthroplasty (THA). One dog had bilateral ALFI.
      Loosening developed at the stem-cement interface a mean of 30 months after THA.
      The most common clinical sign was intermittent subtle or non-weight-bearing
      lameness. On radiographs obtained after THA, the distal stem tip was in contact
      with the cortical endosteum in all dogs. Radiographic changes at the time of
      diagnosis of ALFI included asymmetric periosteal reaction along the femoral
      diaphysis (n = 11), radiolucent zone at the stem-cement interface (6), altered
      implant position (4), and femur fracture (1). Surgical revision resulted in a
      good or excellent outcome in 9 dogs. In 1 dog, the implant became infected. In
      another, aseptic loosening recurred. Aseptic loosening of the femoral implant was
      significantly more common when initial positioning of the implant resulted in
      contact between the distal tip of the implant and cortical endosteum than when
      there was no contact.

PMID- 9290827
TI  - Anesthetic effects of tiletamine-zolazepam, alone or in combination with
      butorphanol, in goats.
AB  - OBJECTIVE: To evaluate anesthetic effects of tiletamine-zolazepam (TZ), alone or
      in combination with butorphanol, in goats undergoing laparotomy for embryo
      collection. DESIGN: Randomized clinical trial with crossover design. ANIMALS: 9
      adult female goats. PROCEDURE: Goats were anesthetized twice: once with TZ (5.5
      mg/kg [2.5 mg/lb] of body weight, i.v.) and once with tiletamine-zolazepam and
      butorphanol (0.1 mg/kg [0.045 mg/lb], i.v.). Additional doses of TZ (0.5 to 1.0
      mg/kg [0.23 to 0.45 mg/lb], i.v.] were administered as needed to maintain a
      surgical anesthetic plane. Time to sternal recumbency was recorded, and quality
      of induction was scored. Arterial pressures, heart rate, respiratory rate, and
      rectal temperature were recorded every 5 minutes; arterial blood samples were
      collected every 30 minutes. Oxygen was insufflated if estimated saturation of
      hemoglobin in peripheral arterial blood with oxygen was < 90%; intermittent
      positive-pressure ventilation was performed if goats became apneic. Muscle
      relaxation, quality of anesthesia, and eye signs were scored every 15 minutes
      during anesthesia. Anesthesia time was recorded, and quality of recovery and
      degree of postoperative analgesia were scored. Plasma cortiso concentration was
      measured before induction, immediately after extubation, and 2 hours after
      extubation. RESULTS: Induction was rapid and smooth. Five goats regurgitated, 3
      required supplemental oxygen, and 1 required intermittent positive-pressure
      ventilation, but none of the goats became hypotensive. Muscle relaxation and
      quality of anesthesia were adequate. Goats recovered from anesthesia without
      complications. We did not detect any significant differences between anesthetic
      regimens for any of the variables measured, except bicarbonate concentration and
      base excess. CLINICAL IMPLICATIONS: TZ at a dose of 5.5 mg/kg was satisfactory
      for anesthetic induction in goats; additional doses can be given to extend
      anesthesia time, but addition of butorphanol at a dose of 0.1 mg/kg to this
      regimen does not seem to provide any measurable benefit. An oxygen source and a
      means of assisting ventilation should be available.

PMID- 9290826
TI  - Isolation of methicillin-resistant Staphylococcus aureus from a postoperative
      wound infection in a horse.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) was isolated from a
      postoperative wound infection in a horse. Methicillin-resistant S aureus
      infections in animals have been reported. In human beings, MRSA is an important
      cause of hospital-acquired (nosocomial) infections. Infections caused by MRSA
      respond poorly to beta-lactam treatment, and resistance of MRSA to multiple
      antimicrobials, including aminoglycosides, macrolides, clindamycin, and
      tetracyclines, is common. Identification of MRSA by routine susceptibility
      testing may be difficult; therefore, techniques for MRSA detection should be
      incorporated by clinicopathology laboratories. Because the number of hospital and
      community-acquired MRSA infections in human beings is increasing, it seems likely
      that MRSA infections in animals will also become more frequent.

PMID- 9290829
TI  - Surgical and nonsurgical correction of uterine torsion in New World camelids: 20
      cases (1990-1996).
AB  - OBJECTIVE: To report clinical findings for New World comelids with uterine
      torsion and to compare results of 3 methods of correction. DESIGN: Retrospective
      case series. ANIMALS: 11 llamas and 3 alpacas with 20 uterine torsions.
      PROCEDURE: Information concerning history, clinical signs, management, and
      postpartum complications was retrieved from medical records. Information
      concerning subsequent reproductive performance was obtained by telephone
      interview of owners. RESULTS: Uterine torsion was corrected by celiotomy (n = 7);
      transvaginal manipulation (5), or rolling the dam (8). Direction of 19 of 20
      torsions was clockwise when viewed from the rear. Retention of fetal membranes
      was reported for 5 camelids that underwent celiotomy, but was not reported in
      camelids after nonsurgical correction. The uterus prolapsed in 1 llama that
      underwent celiotomy and in another that underwent the rolling technique. Although
      2 camelids that underwent celiotomy subsequently failed to conceive, all camelids
      treated by nonsurgical techniques conceived. CLINICAL IMPLICATIONS: Uterine
      torsion in camelids may be diagnosed by methods similar to those used in cattle.
      Surgical and nonsurgical methods can be used to correct torsion, and postpartum
      complications are rare when torsion is corrected by a nonsurgical method.

PMID- 9290830
TI  - Orbital exenteration and placement of a prosthesis in fish.
AB  - OBJECTIVE: To develop a procedure for orbital exenteration and prosthesis
      placement in fish. DESIGN: Prospective study. ANIMALS: 5 cultured hybrid striped
      bass (Morone saxatilis x M chrysops) ranging from 30 to 50 cm in length.
      PROCEDURE: Exenteration was performed, using a dorsal approach in which blunt
      dissection was performed in the circumorbital sulcus. The orbit was then dried,
      and simple interrupted sutures were placed, leaving 2 suture loops within the
      orbit. The orbit was filled with polyvinylsiloxane, and a prosthetic glass eye
      was seated in the polyvinylsiloxane. RESULTS: All fish retained the prosthesis
      and had satisfactory cosmetic results at the end of the 8-week study period.
      CLINICAL IMPLICATIONS: The increase in popularity of pet fish and abundance of
      valuable aquarium and show fish have led to heightened awareness of piscine
      ocular disease. Aquarium fish are often euthanatized because of disfiguring
      ocular problems. The technique described here for surgical exenteration and
      cosmetic orbital prosthesis placement in fish may extend the captive life of
      public display fish.

PMID- 9290831
TI  - Use of electromyography in seven injured wild birds.
AB  - Seven wild birds with traumatic injuries affecting the peripheral nervous system
      were evaluated with the aid of electromyography. Initially, electromyography was
      performed on these birds because of loss of motor control and muscle atrophy that
      could not be explained by clinical signs alone. It can be difficult to assess
      postural reactions and reflexes in these birds. Use of electromyography to
      provide prognostic information for rehabilitation potential had not been
      reported. Reviews in the literature indicate that electromyography in human
      beings helps when assessing prognosis in sports-related injuries. Because wild
      birds require nearly total function for complete rehabilitation,
      electromyographic findings of functional motor units or evidence of axonal
      degeneration can assist in determining their potential for release.

PMID- 9290828
TI  - Ablation of the cranial portion of the preputial cavity in a pig.
AB  - A technique for surgical ablation of the cranial portion of the preputial cavity
      including the preputial diverticulum in pigs is described. The technique was
      performed on a 5-month-old 83.2-kg (183-lb) Hampshire barrow that had ulceration
      and fibrosis of the preputial cavity secondary to chronic preputial
      diverticulitis. The pig recovered without difficulties and was able to urinate
      normally after surgery.

PMID- 9290833
TI  - Powerlessness and HIV prevention among people who trade sex for drugs
      ('strawberries').
AB  - Researchers and members of the drug culture have employed the term 'strawberries'
      to describe African American women who trade sex for drugs. Data from six US
      cities participating in a community-based drug research project were analysed to
      examine the determinants of trading sex for drugs. As shown by our data, some
      African American women match the street description commonly attributed to
      'strawberries'. However, our results also show that trading sexual favours for
      drugs is not limited to African American women, nor solely to women. Rather,
      trading sex for drugs is an economic behaviour that occurs among women and men of
      any race/ethnicity who use crack cocaine. Trading sex for drugs is closely
      related to conditions of poverty and homelessness, conditions that especially
      affect many crack smokers. The discussion urges educators and researchers to be
      alert for 'strawberry behaviours' exhibited by drug-users of any racial/ethnic
      background or gender.

PMID- 9290832
TI  - Sexuality in Montreal women living with HIV.
AB  - The impact of learning a positive HIV test result on the sexuality of 161 women
      (47 injection drug users (IDU), 53 non-IDU women of Haitian or African origin
      (non-IDU-HA), and 61 non-IDU Caucasian women (non-IDU-C) was assessed using
      closed and open-ended questions. Self-reported CD4+ count correlated with any
      post-test (p = 0.001) and past month sexual activity (p = 0.007). After learning
      their HIV status, 110 women (68%) were sexually active, 48 (44%) of these within
      1 month. After resuming sexual activity, 84% underwent a sexual adjustment period
      (median duration 8.5 months). IDU women were more likely to have frequent sex, be
      anorgasmic, and prefer sex less often. Consistent partner condom use was low in
      general (19% for IDU, 30% for non-IDU-HA, and 62% for non-IDU-C) and by partner
      type (new regular partner 58%, same regular partner 36%, casual partner 29%).
      Sexual satisfaction tended to decline post-test and then increase to higher than
      pre-test levels. Counselling focused on the safe and satisfying aspects of sex
      may assist women with HIV infection in sexual decision-making. Facilitating the
      access of IDU women with HIV infection to medically supervised drug provision and
      to detoxification and rehabilitation programmes can weaken the link between drug
      use and sex work.

PMID- 9290835
TI  - Testing and treatment behaviour of HIV-infected women: white, African-American,
      Puerto Rican comparisons.
AB  - Findings from a study of the testing and treatment behaviour and experiences of
      African-American (n = 31), Puerto Rican (n = 30) and non-Hispanic white (n = 23)
      HIV-infected women are reported. All women were 20-45 years of age and had not
      yet been diagnosed with AIDS. Data for the analyses presented were gathered
      through an interviewer-administered questionnaire completed before respondents
      participated in an unstructured interview. The analyses examine race/ethnic
      differences in women's delays in seeking testing and medical care, and in sources
      and types of HIV-treatment. Most significant for primary and secondary prevention
      efforts, the findings suggest that a significant proportion of women who suspect
      they are infected may delay being tested, and further, a substantial proportion
      who learn they are seropositive may delay seeking medical care. Thus important
      opportunities among HIV-infected women for secondary prevention through timely
      antiviral and prophylactic treatment, and for primary prevention through risk
      reduction counselling may be being missed in many cases.

PMID- 9290834
TI  - Reasons for having sex and sexual risk-taking: a study of heterosexual male STD
      clinic patients.
AB  - Individuals report a variety of reasons for having sex. Understanding these
      reasons can improve HIV and STD prevention efforts because they may constitute an
      important component in the aetiology of sexual risk-taking behaviours.
      Relationships between self-reported reasons for having sex and frequency of
      participation in sexual practices among 146 heterosexual men recruited from
      public STD clinics in Southern California were examined. Using a self
      administered questionnaire, respondents reported how often they engaged in sex
      for each of 16 reasons and how frequently they participated in high, moderate,
      and low-risk sexual practices. A principal components analysis identified five
      factors used to construct scales: love; compliance; pleasure; altered states; and
      potency. Higher-risk sexual practices were positively associated with the
      pleasure and potency scales, whereas lower-risk practices were positively
      associated with the love scale. These findings suggest that some reasons men
      report for having sex may influence sexual risk-taking. Interventions to reduce
      unsafe sex should explicitly address how men can practise safer sex and still
      experience pleasure and potency.

PMID- 9290837
TI  - Dynamics of knowledge and attitudes about AIDS among the educated in southern
      India.
AB  - AIDS awareness and attitudes among an educated segment of the Indian population
      were assessed. The study population was a total of 433 students and faculty in
      colleges and universities, and research & technical staff of the Public Health
      Service. While most knew that sexual intercourse (96%) & injection drug use (85%)
      could transmit HIV, and that shaking hands (95%) & mosquitoes (86%) could not,
      63% did not know that breastfeeding was a mode of transmission and 71% falsely
      believed that they could acquire HIV by donating blood. The only variable to
      correlate positively with knowledge was education. Knowledge about true and false
      modes of transmission constituted three distinct dimensions as determined by
      factor analysis. An overwhelming majority (90%) harboured at least one hostile
      view towards persons with AIDS. Knowledge and education independently correlated
      with decreased hostility. There was great concern about the impact of the
      disease: 85% believed that AIDS is a very serious problem in India and 93%
      favoured increased government spending on AIDS education. These results display
      high levels of knowledge (with some gaps), and widespread support for increased
      action.

PMID- 9290836
TI  - Heterosexual behaviour and condom usage in an urban population of Delhi, India.
AB  - A survey conducted among the lower-class urban population of Delhi, India to
      describe the heterosexual behaviour, condom usage and awareness about STDs/AIDS
      revealed that 4.4% respondents had sex outside/before marriage. Female commercial
      sex workers, friends and neighbours were the important sexual partners.
      Heterosexual activity was significantly higher among males, unmarried, literates
      and middle/higher income groups. Almost half of those who had sex before/outside
      marriage never used a condom during the sexual encounter. Though only a small
      fraction of the population was found to be engaged in extra-/pre-marital sex, the
      overall impact of this may be multifold, given the nature and modes of HIV
      transmission. The superficial and inadequate knowledge regarding STDs/AIDS among
      this population, especially among those having extra-/pre-marital sex, indicates
      an urgent need for appropriately targeted health education and condom promotion
      activities in the community with an endeavour to increase awareness about STDs
      and HIV/AIDS and motivate people towards healthy sexual lifestyles.

PMID- 9290839
TI  - Promoting HIV prevention: a problem identification approach to interventions in
      post-HIV test counselling.
AB  - HIV antibody testing now occurs in a wide variety of clinical settings.
      Counselling at the time of HIV testing involves more than obtaining informed
      consent and there can be an active role for HIV prevention strategies. Whilst
      research has not clearly identified the effectiveness of either HIV testing or
      counselling for HIV prevention, HIV testing does allow for focused discussions
      with individuals about risk behaviour. Therefore all efforts to refine
      interventions to enhance HIV prevention must be encouraged. Interventions which
      encourage clients to examine beliefs about behaviours and relationships can bring
      about an increase in perceived choices, and thereby lead to changes in behaviour.
      A model is presented for conducting post-HIV test counselling for use by health
      professionals involved in HIV testing. Examples of questions and question styles
      are provided to illustrate this framework which addresses prevailing beliefs and
      encourages contributions from clients.

PMID- 9290838
TI  - Environmental change and organizational evolution: reconsidering the niche of
      community-based AIDS organizations.
AB  - This paper examines the changing role of AIDS service organizations (ASOs) in the
      provision of community-based HIV services. The paper draws on a study of the
      development of ASOs that is based on in-depth interviews with about 250
      individuals involved in the provision of HIV-related community-based services in
      12 cities in Canada. Findings indicate how the broadening and increasingly
      complex needs confronting ASO workers are leading them to become more focused in
      their efforts. The paper also shows how ASOs are having to reassess their ties to
      other service organizations and, often, to redefine their mandate in the light of
      the changing needs associated with HIV. The paper explores some of the problems
      associated with these changes, and suggests how changing service needs require a
      renewed commitment on the part of ASOs to work at the level of advocacy and
      political change.

PMID- 9290840
TI  - Prevention of blindness in leprosy: an overview of the relevant clinical and
      programme-planning issues.
AB  - Visual disability continues to be a significant problem in leprosy patients due
      to cataract, chronic iridocyclitis, and corneal disease. Clinical and
      epidemiological aspects of these problems are described and the current status of
      eye care in leprosy programmes is discussed.

PMID- 9290841
TI  - Unstable, low-level transmission of malaria on the Colombian Pacific Coast.
AB  - The development of immune responses to malarial infection in inhabitants of
      endemic areas differs according to the level of exposure to the parasite. Adults
      living in a region where the level of malaria transmission is low (Colombia) have
      been shown to exhibit a similar response to each of the three regions of the
      circumsporozoite protein (the central repeated NANP region, and the flanking N-
      and C-termini). Conversely, donors exposed to a frequent sporozoite challenge in
      areas of high malaria transmission (Mali) exhibit antibodies predominantly to the
      NANP repeated domain. Malaria in the people of Zacarias, a community on the
      Pacific Coast of Colombia where malaria transmission is low and unstable, was the
      subject of the present study. Within a 9-year period, a negative correlation
      between rainfall and documented malaria cases was recorded for this area. Thick
      smears of blood samples of 319 individuals revealed that 8.5% had malarial
      infections. As most (67%) of the smear-positive cases were asymptomatic, it seems
      that, despite the low prevalence of malaria in this area, the establishment of
      clinical symptoms is attenuated, probably because of the acquisition of
      premunition. Within this region, the most commonly found Anopheles species
      (representing 61.1% of the mosquitoes caught) and that giving the highest monthly
      biting rate (4.0 bites/man) was An. neivai. Most (90%) of the human sera tested
      possessed antibodies to blood-stage forms of Plasmodium falciparum, and 18% had
      antibodies to sporozoites. More than half (58%) of the adults had been in contact
      with hepatitis B virus, 7.2% carried hepatitis B surface antigen, and syphilis
      was common but no subject was found to be seropositive for HIV. A better
      understanding of the dynamics of the different elements influencing malaria in
      areas of low, unstable transmission, such as the one described here, is essential
      for the design of new malaria-control strategies.

PMID- 9290842
TI  - Palpation as a method of fever determination in Malawian children who are less
      than 5 years old: how reliable is it?
AB  - Fever is a common occurrence in children who are < 5 years old and palpation of
      the forehead may or may not be a reliable method for determining fever in such
      children. In a study of 1120 Malawian children of this age attending outpatient's
      clinics, each child's mother and a clinical officer (CO) were asked to palpate
      the child's forehead and decide whether the child was febrile (felt warm or very
      warm) or afebrile (felt normal). The rectal temperature of each child was then
      taken using a thermometer and the child considered febrile if this temperature
      was > or = 38 degrees C. Using palpation, mothers judged 973 (86.9%) of 1120
      children to be febrile and CO judged 565 (50.4%) of 1118 to be febrile, whereas
      thermometer readings indicated 410 (36.7%) to be truly febrile. False-positives
      (i.e. afebrile children judged to be febrile by palpation) accounted for 574
      (59.0%) of the 973 children who were considered febrile by their mothers and 228
      (40.4%) of the 565 children so considered by CO; mothers reported significantly
      more false-positives than CO (P < 0.05). False-negatives (i.e. febrile children
      judged to be afebrile by palpation) accounted for 11 (7.5%) of the 147 children
      who were considered afebrile by their mothers and 73 (13.2%) of the 553 children
      so considered by CO; CO reported significantly more false-negatives than mothers
      (P < 0.05). Overall, mothers were as likely as CO to misjudge a child (721/1120
      v. 781/1118; P > 0.05). Although the sensitivity of mothers and CO in determining
      fever was similar (97.3% v. 82.2%; P > 0.05), CO gave a higher degree of
      specificity than the mothers (67.8% v. 19.2%; P < 0.000001). Although the present
      results indicate that palpation is not a reliable method of determining fever in
      children who are < 5 years old, caregivers should continue to use palpation as a
      useful first step in deciding when a child needs to be referred.

PMID- 9290843
TI  - The effects of infection with Plasmodium yoelii nigeriensis on the reproductive
      fitness of Anopheles stephensi.
AB  - Infection with the rodent malarial parasite Plasmodium yoelii nigeriensis caused
      a significant reduction in the reproductive fitness (number of eggs produced and
      proportion of eggs hatched) of two different generations of Anopheles stephensi.
      Overall fertility (number of larvae produced) was reduced by 38.3% in the
      generation containing smaller mosquitoes (with a wing length of 3.2 +/- 0.1 mm)
      with relatively larger parasite burdens, and by 48.81% in the generation
      containing larger mosquitoes (with a wing length of 3.4 +/- 0.1 mm). The
      contribution that reduction in egg production and egg hatching made to overall
      reduction in reproductive fitness differed in each experiment. No significant
      difference was observed in the egg size (length from tip to tip and breadth at
      the centre) of control and infected mosquitoes in another generation of infected
      An. stephensi.

PMID- 9290844
TI  - Observations on compatibility between Bulinus truncatus and Schistosoma
      haematobium in the Senegal River Basin.
AB  - In experiments to determine the compatibility between isolates of Schistosoma
      haematobium and Bulinus truncatus from Mali and Senegal, the parasite isolates
      were shown to differ in their intermediate host specificity. Bulinus truncatus
      from the Lower and Middle Valleys (Senegal) and the Upper Valley (Mali) of the
      Senegal River Basin (SRB) were all susceptible to S. haematobium isolated from
      the urines of children living in Tenegue, Office du Niger, Mali. However, none of
      the B. truncatus tested was susceptible to a parasite isolated from children
      living in Mbodiene, a village in the Lower Valley of the SRB, where natural
      transmission is normally associated with B. globosus. As B. truncatus is widely
      distributed in the SRB, the possible appearance of a Bulinus-truncatus-borne
      parasite in the Middle and Lower Valleys should be carefully monitored.

PMID- 9290845
TI  - Country-wide rapid epidemiological mapping of onchocerciasis (REMO) in Cameroon.
AB  - The prevalence of infection in local communities has been used as the basis for
      the country-wide repartition of onchocerciasis in Cameroon, following the
      principles for rapid epidemiological mapping of onchocerciasis (REMO) developed
      by the World Health Organization. The levels of endemicity were evaluated in 349
      villages by rapid epidemiological assessment (REA), a method based on the
      examination of nodules in males aged > or = 20 years. An onchocerciasis map was
      then drawn from the epidemiological data which had been collected previously,
      from clinico-parasitological surveys based on the examination of skin snips, and
      the results of the REA surveys. The REMO surveys allowed the main onchocerciasis
      foci in Cameroon to be accurately delineated, and several small endemic areas
      which had never been reported before to be identified. The total 'at risk'
      population (i.e. those for which ivermectin treatment should be considered as
      urgent or highly desirable) was estimated by combining the epidemiological
      results and the demographical data available from an administrative census. Those
      at risk were estimated to number 3.5 million, representing about 50% of the total
      rural population in Cameroon.

PMID- 9290846
TI  - The entry of ivermectin and suramin into Onchocerca ochengi nodules.
AB  - No currently available drug, which is safe for mass treatment, effectively kills
      adults of Onchocerca volvulus, the causal agent of onchocerciasis in humans, or
      of O. ochengi, a cattle parasite used as a model of O. volvulus. Since adults of
      both of these filarial nematodes are found in well developed nodules, the lack of
      efficacy of these drugs may be a result of their poor penetration into the
      nodules. To check if this was the problem, the distributions of the
      microfilaricide, ivermectin, and the partial macrofilaricide, suramin, in plasma,
      skin, nodule capsules and nodule contents were determined in cattle naturally
      infected with O. ochengi in Cameroon. The cattle were treated with either a
      single, subcutaneous injection of 500 micrograms ivermectin/kg, or with
      intravenous injections of [14C]-labelled suramin, each of 10 mg/kg, given one a
      day for 6 days. Concentrations of ivermectin and suramin in various tissues were
      then assayed by high-pressure liquid chromatography and scintillation counting,
      respectively. On day 7 post-treatment (pt), suramin concentrations were
      consistently highest in the nodule, contents and capsule wall (11.0 and 8.9
      nCi/g, respectively) and significantly less in skin and plasma (1.2 and 1.4
      nCi/g, respectively; P < 0.05). The distribution of ivermectin on day 7 pt was
      similar, with the highest concentrations in the capsule wall, nodule contents and
      plasma (58.4 ng/g, 43 ng/g and 48.6 ng/ml, respectively; P > 0.05) and the
      concentration in the skin (6.4 ng/g) significantly lower than those in the
      capsule or plasma (P < 0.05). High intra-nodular concentrations of both drugs
      were maintained for 5-7 days at least and those of ivermectin would be expected
      to kill nematodes other than filariae. It is apparent that failure of ivermectin
      and suramin to kill adult Onchocerca spp. is not because the drugs penetrate
      nodules inadequately.

PMID- 9290847
TI  - The intermediate hosts of Dracunculus medinensis in northern region, Ghana.
AB  - Cyclopoid copepods were collected over a period of 17 months from six man-made
      water reservoirs in an area of northern Ghana where dracunculiasis is endemic.
      The numbers and species of cyclopoid copepods as well as the species naturally
      infected with Dracunculus medinensis larvae were recorded at fortinightly
      intervals. The occurrence of copepods was compared with concurrent rainfall and
      with monthly incidences of dracunculiasis in the year after the reservoir survey.
      Seven species and two subspecies of copepods were found in the study area:
      Thermocyclops neglectus decipiens, T. crassu' consimilis, T. incisus, T.
      inopinus, T. emini, Mesocyclops major, M. ogunnus, M. kieferi and Cryptocyclops
      linjanticus. More than 60% of all the cyclopoids found were T. n. decipiens and
      only four species (T. incisus, T. inopinus, T. n. decipiens and M. kieferi) were
      found infected. Infection rates were very low (< or = 0.3%). The seasonal
      fluctuations of cyclopoid copepods showed different patterns in the six
      reservoirs, perhaps related to local circumstances not investigated in the
      present study. As the people in the study area are very mobile during the
      dracunculiasis transmission season, it seems likely that some of them become
      infected at water sources other than the ones investigated. It was therefore
      difficult to correlate occurrence of cyclopoid copepods in the local water
      sources with the prevalence of the human infection in the catchment area. No
      conclusion as to the most important intermediate host(s) in the area could be
      made.

PMID- 9290848
TI  - Epidemiological survey of infection with hepatitis B virus in the savannah and
      wetlands (Pantanal) of central Brazil.
AB  - An epidemiological survey of the prevalence of hepatitis B virus (HBV) was
      conducted in the county of Nossa Senhora do Livramento, Mato Grosso state,
      central Brazil. This rural county has a largely stationary population of low
      socio-economic status, and is divided into savannah-type vegetation and wetland.
      Overall, 740 subjects aged > 9 years were selected at random, interviewed and
      bled so that seropositivities of various HBV markers (surface antigen and
      antibodies to this antigen and to core antigen) could be determined. At least one
      marker was found in 169 (22.8%) of the subjects but only nine (1.2%) carried the
      surface antigen. Vegetation type (wetland v. savannah) was not associated with
      HBV infection but male gender, increasing age, and having had sexual experience
      were each associated with the infection. The prevalence of HBV markers was higher
      in immigrants (32.5%) than in native individuals (21.1%), many immigrants
      apparently having acquired the infection before settling in the study area.

PMID- 9290849
TI  - Phlebotomine sandflies of Kenya (Diptera: Psychodidae). V. Phlebotomus
      (Paraphlebotomus) mireillae n.sp.
AB  - A new species of the sandfly subgenus Paraphlebotomus Theodor from Kenya is
      described and named Phlebotomus mireillae. The type locality is Utut Reserve,
      near Gilgil, Nakuru District. The description is based on 10 males and 10 females
      reared from individual egg batches of wild-caught females. Males of the new
      species differ from nine other species of the subgenus by the shape of the
      aedeagus, which is straight, not curved or hooked. They are separated from the
      remaining three species by other differences in the aedeagus, and in the style
      and coxite process. Female P. mireillae have backwardly pointing spines inside
      the distal quarter of the spermathecal ducts, a character not previously
      described for phlebotomine sandflies. Additional characters which distinguish
      females of the new species from others of the subgenus are differences in the
      pharyngeal armature and spermathecae and the lengths of the third antennal
      segment and labium.

PMID- 9290850
TI  - Influence of storage temperature on estimates of tumour necrosis factor in plasma
      samples from patients with cerebral malaria.

PMID- 9290851
TI  - HIV/Leishmania co-infections in Portugal: diagnosis and isoenzyme
      characterization of Leishmania.

PMID- 9290852
TI  - Observations on the formation of new onchocercal nodules in Ecuador.

PMID- 9290853
TI  - Nectar from a wax plant, Hoya sp., as a carbohydrate source for Lutzomyia
      longipalpis (Diptera: Psychodidae).

PMID- 9290854
TI  - Lifetime comorbidity of alcohol dependence in women with bulimia nervosa.
AB  - To determine how women with comorbid bulimia nervosa and alcohol dependence
      differed from those with bulimia nervosa alone, 114 women with DSM-III-R bulimia
      nervosa were assessed at intake for a randomized clinical trial with structure
      diagnostic interviews and psychometric instruments. The sample was divided on the
      basis of the presence (47%) or absence (53%) of lifetime alcohol dependence. Axis
      I and Axis II disorders, clinical features of bulimia, and personality and
      temperament characteristics were then compared. Women with comorbid alcohol
      dependence and bulimia nervosa reported a higher prevalence of suicide attempts,
      anxiety disorders, other substance dependence, conduct disorder and personality
      disorders (especially borderline and histrionic), and higher scores on novelty
      seeking, impulsivity, and immature defenses. There were few differences in the
      severity of bulimic symptoms. Findings revealed that women with comorbid bulimia
      nervosa and alcohol dependence bear a greater burden of Axis I and Axis II
      psychopathology and display greater symptoms of impulsivity and novelty seeking.

PMID- 9290855
TI  - Client perceptions of incest and substance abuse.
AB  - Clients receiving substance abuse treatment from 35 treatment facilities
      throughout the United States were surveyed using the Substance Abuse and Incest
      Survey-Revised (SAIS-R). A total of 732 participants responded to the survey; 518
      (71%) were males, 204 (28%) were females, and 10 (1%) did not indicate gender.
      Participants had a mean age of 33.8 years, were predominately Caucasian (61.6%),
      never married (45.2%), were currently unemployed (69.4%), and had completed an
      average of 11.7 years of education. Of the entire sample, 266 (36.3%) reported
      having been victims of incest; 151 were males and 113 were females (2 did not
      indicate gender). The group reporting incest histories had a significantly
      greater percentage of females that did the group not reporting incest histories
      (chi 2 = 48.1, p < .001). Participants with incest histories were asked about
      their perceptions regarding incest, substance abuse, and counseling. Item
      responses were examined using descriptive statistics and factor analysis. The
      factor analysis on SAIS-R perception items identified five factors that accounted
      for 68.9% of the variance; these factors were Stigma and Resistance to
      Counseling; Substance Abuse and Incest; Ambivalence; Fear and Anticipation; and
      Receptivity to Counseling. Results are presented and the implications for
      substance abuse treatment and counseling are discussed.

PMID- 9290856
TI  - Effects of negative outcome on food consumption in college women with and without
      troubled eating patterns.
AB  - This study looked at the effects that failure experiences have on food
      consumption and their effect on college women. Part I of the study (N = 169) was
      used to screen subjects for Part II (N = 55) based on scores on the Bulimia Test
      Revised. In part II, eating-disordered and control participants completed one of
      two types of tasks-a negative outcome and a neutral outcome control task.
      Following the task, a bogus cookie rating task provided the opportunity for
      participants to eat chocolate chip cookies. Mood was assessed throughout Part II.
      Results indicate that mood was more negative following the negative outcome task.
      Eating-disordered participants ate more than did controls in this same condition;
      these participants also reported improved mood after eating.

PMID- 9290857
TI  - Measuring excessive alcohol use in college drinking contexts: the Drinking
      Context Scale.
AB  - Research on youthful drinking has shown that the greatest risks associated with
      alcohol abuse are related to contextual factors that may potentiate heavy
      drinking as well as increase risks for adverse consequences. These contextual
      factors include interacting psychological, interpersonal, and environmental
      dimensions of alcohol use. However, despite considerable college drinking
      research to identify these factors, few formal instruments have been produced for
      measuring excessive drinking in multidimensional contexts. The current study of
      197 college students who were cited their first time for breaking university
      drinking rules focuses on the development and validation of a scale for measuring
      the likelihood of excessive drinking across an array of psychological,
      interpersonal and situational contexts resulting in the 23-item Drinking Context
      Scale (DCS). Three distinct factors emerged defining Convivial drinking, Private
      Intimate drinking, and drinking as a form of Negative Coping. These three factors
      explained 61.5% of the variance after principal components analysis and varimax
      rotation, showed excellent internal reliabilities, and were moderately
      intercorrelated. MANOVA analysis demonstrated concurrent validity with the
      Quality Frequency Index (QFI) and a modified version of the Michigan Alcoholism
      Screening Test (MAST). Implications for further research with the DCS are
      suggested.

PMID- 9290858
TI  - A test of socioeconomic status as a predictor of initial marijuana use.
AB  - The current study examined the effects of socioeconomic status (SES) on
      adolescent marijuana use using data from a national longitudinal survey of
      subjects aged 11 to 17 (N = 1,725). Both direct and indirect measures of SES
      (e.g., Hollingshead's measure of SES, predicts marijuana use among adolescents.
      For males, our study found a nonlinear relationship between the Hollingshead
      measure and marijuana use that had not been identified in previous research. For
      females, the Hollingshead measure was nonsignificant when alcohol use and having
      friends who use marijuana were added to the model. This finding suggests that the
      effects of SES on marijuana use may be mediated by alcohol use and friends' use
      of marijuana. Weekly alcohol users were much more likely than nonusers to
      initiate marijuana use for both males (Odds ratio [OR] = 18.28, Confidence
      interval [CI] = 4.93-67.81) and females (OR = 11.75, CI = 3.22-42.86). Other
      significant variables for both sexes included having a job, having friends who
      use marijuana, and having used some alcohol in the past year. For males, grade
      point average (GPA), commitment to friends, urbanicity, time spent with friends,
      and peer strain were also significant predictors of initial marijuana use. For
      females, prior victimization and low school aspirations were significant. In sum,
      our findings suggest that psychosocial risk factors for marijuana use are
      substantially different for males than for females and that future researchers
      need to test for nonlinear relationships between SES and adolescent substance
      use.

PMID- 9290859
TI  - Attitudes toward bulimic behaviors in two generations: the role of knowledge,
      body mass, gender, and bulimic symptomatology.
AB  - The perceived commonality and acceptability of symptoms of bulimia, as well as
      associated variables including gender, generation, knowledge of bulimia, body
      mass index, and bulimic symptomatology, were assessed. These views were explored
      in a sample of college students (N = 155 male; N = 173 female) and their parents
      (N = 194 mothers; N = 163 fathers). Females perceived bulimic symptoms to be more
      common than males, and students perceived them to be more common than their
      parents. Students perceived bulimic symptoms to be more acceptable than their
      parents. Females had higher levels of bulimic symptomatology, particularly
      daughters. Stepwise simultaneous regression analyses revealed that one's own
      level of bulimic symptomatology was the primary predictor of one's attitudes
      toward the commonality and acceptability of bulimic symptoms. Bulimic
      symptomatology was primarily predicted from perceptions of the acceptability of
      bulimic symptoms and body mass index. Results suggest that college-age students
      may be at greater risk for the development of bulimia nervosa because of their
      greater tolerance of these symptoms; alternatively, people endorsing higher
      levels of bulimic symptomatology may adjust their attitudes, perceiving bulimic
      symptoms to be more tolerable, in order to alleviate the dissonance between their
      attitudes and behaviors.

PMID- 9290860
TI  - Selective processing of visual alcohol cues in abstinent alcoholics: an approach
      avoidance conflict?
AB  - When symptomatic individuals selectively attend to emotionally relevant stimuli,
      the ability to shift attention away from such material is impaired. Subjects may,
      however, seek to avoid further processing of these stimuli, which would
      facilitate attentional shifts. This was examined in a group of abstinent
      alcoholics' responses to stimuli related to alcohol. Eight alcohol and eight
      neutral words served as cues in a covert attention task. The cues were either
      valid (2/3 of trials) or invalid (1/3 of trials) indicators of where a response
      target would appear after 100 or 500 milliseconds. The short interval was
      expected to interact with an initial approach toward the alcohol word, while the
      long interval would interact with a subsequent avoidance of the stimulus. As
      predicted, the alcoholics showed slower reaction times (RTs) to targets invalidly
      cued by alcohol words in the short interval, reflecting increased difficulties to
      shift attention. However, the alcoholics demonstrated faster RTs to targets
      invalidly cued by the alcohol words in the long interval. This indicates that the
      alcohol cue elicited emotional associations that, subsequent to initial stimulus
      identification, trigger an interrupting function of the attentional system.

PMID- 9290861
TI  - Gender differences in the outcome of an unaided smoking cessation attempt.
AB  - There is conflicting evidence concerning gender differences in success at
      quitting smoking. Information is especially lacking regarding gender differences
      among unaided quitters who make up the vast majority of those attempting to quit.
      One hundred thirty-five smokers who made an unaided attempt at quitting were
      interviewed before quitting and were followed for 1 year after cessation. Relapse
      rates were extremely high both for men and women, with 62% of participants
      returning to regular smoking within 15 days after cessation. Women and men were
      equally likely to maintain short-term abstinence (through 15 days), but women
      were more than three times as likely to relapse subsequently. Nine percent of
      men, but no women, had biochemically verified sustained abstinence throughout the
      1-year follow-up period. For both men and women, any smoking after the quit
      attempt inevitably led to full-blown relapse. Most participants resumed regular
      smoking within 24 hours after the first episode of smoking. Gender differences
      were observed for several variables related to smoking history, demographics,
      social support, perceived stress, and motivational factors, but these differences
      did not explain the increased risk of relapse for women. Our results clearly
      indicate that women are less likely than men to maintain long-term smoking
      abstinence following an unaided quit attempt, but reasons for this gender
      difference need further exploration.

PMID- 9290862
TI  - Persistence predicts latency to relapse following inpatient treatment for alcohol
      dependence.
AB  - Male alcoholics (N = 85) were followed for 6 months after inpatient treatment for
      alcohol dependence. Latency to relapse was predicted by two related persistence
      measures (the RD2 Persistence scale and the Orderliness/Persistence factor scale
      of the Tridimensional Personality Questionnaire, TPQ) as well as by job status at
      the time of admission to treatment, a history of vagrancy or public intoxication,
      amount of prior substance abuse treatment and the number of criteria met for a
      diagnosis of Antisocial Personality Disorder. Persistence predicted relapse
      latency even when the other predictors were used as covariates, supporting the
      hypothesis that normal-range personality variables may enhance the prediction of
      clinical outcome. Further, the relations between TPQ scales and antisocial
      behavior as well as the severity of alcohol dependence were examined.

PMID- 9290863
TI  - Psychopathology and personality of young women who experience food cravings.
AB  - The objective of the present study was to investigate the psychopathology and
      personality characteristics of women who experience food cravings. A total of 101
      young women selected at random from the community completed the Diagnostic
      Interview for Genetic Studies with a trained interviewer. The interview included
      a section about food-craving experiences and associated factors. Subjects also
      completed a self-report questionnaire booklet containing the Temperament and
      Character Inventory (TCI) and the Eating Disorder Inventory (EDI). Compared to
      noncravers, women who reported food cravings were significantly more likely to
      report a history of alcohol abuse/dependence (p = .003), significant weight
      changes (p = .003), and to have undertaken dieting (p = .02), bingeing (p = .05),
      vomiting (p = .02), exercise (p = .04), diet pill (p = .03), and laxative use (p
      = .01) to control weight. There was a trend for the cravers to have higher
      novelty-seeking scores on the TCI (p = .06). Our findings suggest that women who
      experience food cravings are more likely to have met criteria for alcohol
      abuse/dependence and tend to have temperament characterized by higher levels of
      novelty seeking. In addition the high rates of eating-disorder symptomatology
      implies overconcern with body weight and shape in the women who experienced food
      cravings.

PMID- 9290864
TI  - The Inventory of Drinking Situations (IDS) in current drinkers with different
      degrees of alcohol problems.
AB  - The Inventory of Drinking Situations (IDS) is a questionnaire developed to
      characterize the situations where alcoholics in treatment drank excessively. The
      purpose of the present study was to extend the understanding of this instrument
      as a research and diagnostic tool by applying it to drinking situations in
      individuals who have never been diagnosed as alcoholics, but who may have
      problems due to alcohol. Seventy-three current drinkers (32.1 +/- 9.98 years)
      were examined with a version of the IDS suitable for nonalcoholic individuals.
      Using the CAGE test we categorized the subjects in five groups according to their
      score. Correlational analysis revealed that the IDS subscale scores increased
      significantly with the severity of drinking problems. The CAGE score, the factor
      derived scale Negative Situations, being male, and a preference for drinking
      alone were also correlated with the amount of alcohol consumed, while age was
      correlated with none of the variables of interest. To facilitate the analysis of
      the profiles of drinking situations, the IDS subscales underwent a factor
      analysis that rendered two factor-derived scales, suggesting that drinking occurs
      both in positive and in negative situations. In persons with more alcohol
      problems, according to their high CAGE scores, there was more drinking in
      negative situations that in positive ones. Accordingly, we confirmed that the
      profiles of drinking situations seen in problem drinkers indicated that
      situations related to negative emotions are more important determinants to drink.
      Implications of a shift from drinking in positive to drinking in negative
      emotional situations are discussed. We further substantiated the value of this
      test instrument for studies on drinking situations and for studies in
      nonalcoholic individuals.

PMID- 9290865
TI  - Self-efficacy, attendance, and weight loss in obesity treatment.
AB  - Self-efficacy is an important predictor of treatment outcomes for a variety of
      addictive behaviors. However, little research is available regarding its
      predictive value in obesity treatment. We assessed the predictive validity of the
      20-item version of the Weight Efficacy Lifestyle Questionnaire (WEL) in a
      consecutive sample of 109 obese adults seeking outpatient treatment at a
      university-based weight-management center. Although the WEL demonstrated a stable
      factor structure and sound psychometric properties, it failed to correlate with
      either program attendance or weight loss. We concluded that self-efficacy
      judgments (as measured by the WEL) are not predictive of short-term obesity
      treatment outcomes.

PMID- 9290866
TI  - Environmental events surrounding natural recovery from obesity.
AB  - Studying environmental contexts surrounding weight loss without treatment may aid
      the development of interventions to facilitate the natural forces that support
      behavior change. Event occurrences surrounding natural recovery from obesity were
      investigated using formerly obese persons (n = 21) who had lengthy problem
      histories (4 years minimum) and who had maintained stable weight loss for a mean
      of 4.5 years. Currently obese persons with similar weight histories served as
      controls (n = 20). Collaterals verified participants' weight histories and
      absence of interventions. During structured interviews, event occurrences were
      assessed over a 4-year period that began before weight loss and continued through
      the first year of maintenance. Controls recalled events over a comparable
      interval that equated the groups on the length of recall. Recovery was associated
      with fewer intimate relations events prior to weight loss and with decreased
      negative events related to weight, family relations, and social activities after
      weight loss. Positive events increased during active weight loss. These findings
      suggest that successful behavior change is a lengthy process that extends beyond
      active weight loss and is dependent on the surrounding environment.

PMID- 9290867
TI  - Mind your manners. Part I: History of death certification and manner of death
      classification.
AB  - Every death is unique, but deaths also share similar features that allow them to
      be grouped into categories. Since its initial description over 800 years ago, the
      position of coroner has been charged with the determination of manner of death.
      This determination has been made by examination into the circumstances
      surrounding death and of wounds on the surface of the body. Over the years,
      physicians have gained sufficient understanding of the body such that the autopsy
      became an important part of a death investigation. With additional time, laws
      were changed so that individuals charged with the determination of manner of
      death were required to have appropriate training. Death certification is the
      means by which deaths are grouped together according to similar characteristics.
      The practice of death certification has led to effective public health programs
      and the advancement of medical science. The addition of manner of death to the
      death certificate is an American contribution to vital statistics registration.
      The purpose of the autopsy report differs from that of the death certificate; the
      report fully addresses the unique aspects of a death, while the certificate
      captures the essence of the circumstances surrounding death in a few words.

PMID- 9290868
TI  - Mind your manners. Part II: General results from the National Association of
      Medical Examiners Manner of Death Questionnaire, 1995.
AB  - More than 700 physician medical examiner/coroners (ME/Cs) were surveyed to assess
      differences in manner of death classifications for typical but often
      controversial death scenarios: 198 physicians participated by choosing the manner
      of death (homicide, suicide, accident, natural, undetermined) for 23 such
      scenarios. Sixteen questions related to death certificate training, work
      location, and manner of death issues were also asked. The classification of
      manner of death by ME/Cs was highly variable. For some challenging death
      scenarios, majority agreement was lacking. Agreement was > or = 80% for only 11
      of the 23 scenarios and was 100% for only 1. Manner of death classification
      method was not influenced by forensic pathology board certification status, by
      whether or not the physician actually completed death certificates, or by
      previous threats of lawsuits over manner of death classification. However, there
      were some differences by state. No textbook or individual was widely recognized
      as authoritative on manner of death issues. Few ME/Cs had formal death
      certification training in medical school or residency. The data lend credence to
      the practice of the National Center for Health Statistics (NCHS) of classifying
      manner of death for statistical purposes by using coding and classification rules
      and selection criteria rather than solely on the basis of the classification of
      manner chosen by ME/Cs. The data also indicate that caution is in order when one
      compares manner of death statistics of one ME/C with those of another Published
      guidelines and more uniform training are needed so that ME/Cs may become more
      consistent in their manner of death classifications. Further information is
      presented in Part I (history of manner of death classification) and in Part III
      (individual death scenarios and their analysis) companion articles in this issue
      of the Journal.

PMID- 9290869
TI  - Mind your manners. Part III: Individual scenario results and discussion of the
      National Association of Medical Examiners Manner of Death Questionnaire, 1995.
AB  - In 1995, a questionnaire was distributed to the > 700 physician medical
      examiner/coroners (ME/Cs) who are members of the National Association of Medical
      Examiners (NAME, St. Louis, MO, U.S.A.). The questionnaire consisted of 23 death
      scenarios for which individual responders were asked to assign a manner of death
      (homicide, suicide, accident, natural, or undetermined); 198 questionnaires were
      completed and analyzed. The distribution of manner of death responses was
      tabulated. In addition, a nosologist from the National Center for Health
      Statistics was provided with a cause-of-death statement based on each scenario
      and was asked to assign an International Classification of Diseases (ICD) code
      for the underlying cause of death, from which a manner of death was inferred from
      the ICD code's literal text description. Overall, agreement on a given manner of
      death in a single scenario was > 90% in only 4 of 23 scenarios and > 70% in only
      12 of 23 scenarios. However, in 21 scenarios, the most common response comprised
      a majority. The manner of death inferred from the ICD code that was assigned by
      the National Center for Health Statistics (NCHS) matched the most common response
      of participants in 18 of the 23 scenarios. The questionnaire results show that
      there is substantial disagreement among experienced MEs concerning the manner of
      death classification that is preferred for selected types of death. Encouraging,
      however, is the fact that the manner of death coded for statistical purposes
      generally agreed with the most common classification of manner made by ME/Cs.
      Highlights from the discussion of each scenario that occurred during the NAME
      interim meeting (Nashville, Tennessee, February 1996) are also included. Other
      portions of the program including history of manner of death concepts and results
      of questions regarding responder training and characteristics are published
      separately in this issue of the Journal. Information derived from the
      questionnaire should be useful to those planning strategies to improve the
      consistency of manner of death classifications by ME/Cs.

PMID- 9290870
TI  - Site-to-site variability of drug concentrations in skeletal muscle.
AB  - The homogeneity of drug concentrations in skeletal muscle was assessed in eight
      fatal overdoses. Ten to 30 random samples were taken from leg muscle weighing
      1,650 to 7,985 g. For cases involving paracetamol the mean muscle-to-blood ratio
      ranged from 0.1 to 1.1 (n = 4) for amitriptyline 1.1 to 3.6 (n = 3), and for
      dothiepin 0.8 to 2.1 (n = 2). The coefficient of variance was large for all
      drugs, ranging from 10.5 (carbamazepine) to 50 (thioridazine). Skeletal muscle is
      not homogeneous with respect to drug concentrations in fatal overdose cases. Of
      16 instances of drug detection in blood 2 (nortriptyline and promethazine) were
      not detected in muscle. Muscle-to-blood drug ratios varied significantly among
      cases, possibly influenced by survival time after drug ingestion. Quantitative
      interpretations of muscle drug levels present significant difficulties. However,
      skeletal muscle can be used for qualitative corroboration of blood analyses and
      is a suitable specimen for drug detection where none other is available.

PMID- 9290871
TI  - Traumatic carotid artery dissection.
AB  - Traumatic carotid artery dissection is rarely seen as a cause of death in the
      forensic setting. Three cases of traumatic carotid artery dissection that
      demonstrate many of the typical features are presented. There is usually a
      history of some violent trauma to the head or neck, motor vehicle accidents being
      the commonest cause. The carotid artery may be injured anywhere from the common
      carotid portion to the cavernous sinus, resulting in infarction of the
      corresponding cerebral hemisphere. Clinically, symptoms may include loss of
      consciousness, hemiparesis, aphasia, and Horner's syndrome, these typically
      occurring after an interval of hours to days. Carotid artery injury may not be
      associated with evidence of external injury and initially may go undetected or
      may be misinterpreted in the setting of associated neck or head trauma. The
      commonest mechanisms are thought to be blunt neck trauma and neck hyperextension.
      The cases presented highlight the importance of early diagnosis if surgery is to
      be possible to avoid a fatal outcome.

PMID- 9290872
TI  - Fatal head injuries in ground-level falls.
AB  - We analyzed 75 cases of fatal ground-level falls that were investigated by the
      King County Medical Examiner over a 48-month period, with autopsies performed on
      87% of the deaths: 69% of the cases were men and 61% occurred in ages > or = 70
      years; only 12% were aged < 50 years, with the youngest aged 28 years. Most of
      the falls occurred in or about the residence, and many individuals were known to
      have fallen onto hard surfaces. In 77% of cases there was significant pre
      existing natural disease, mostly cardiovascular disease. Liver disease was more
      frequently a contributing factor in those aged < 50 years. Ethanol was present in
      48% of those cases tested, more frequently present in men than in women. Basal
      skull fractures were present in 37% of cases, and acute subdural hematomas, the
      most common intracranial lesion, were present in 85%. We concluded that fatal
      ground-level falls were much more common in elderly persons, owing to a greater
      predisposition to falling, as well as intrinsic age-related changes, including a
      greater susceptibility to acute subdural hematoma.

PMID- 9290873
TI  - Injury patterns in aviation-related fatalities. Implications for preventive
      strategies.
AB  - Autopsy data from individual aviation crashes have long been used in aviation
      safety research in the form of case reports and case series studies. Injuries
      sustained from aviation crashes, however, have not been well documented at a
      national level. This study examines the injury patterns for persons who died in
      aviation crashes in the United States and the implications for preventive
      strategies. Death certificate data for all aviation-related fatalities for the
      years 1980 (n = 1,543) and 1990 (n = 1.011) were obtained from the National
      Center for Health Statistics. The immediate cause of death and all injury
      diagnoses recorded on the death certificates were analyzed in relation to year of
      injury, crash category, and type of victim. Despite a 34% reduction in the number
      of aviation-related fatalities between 1980 and 1990, injury patterns were fairly
      stable. Multiple injuries were listed as the immediate cause of death in 42% of
      the fatalities, followed by head injury (22%); internal injury of thorax,
      abdomen, or pelvis (12%); burns (4%); and drowning (3%). Head injuries were most
      common among children. The majority (86%) died at the scene or were dead on
      arrival at the hospital. Eighteen percent of the victims were reported to have
      sustained a single injury, with head injury being the cause of death in nearly a
      third of these fatalities. Blunt injuries resulting from deceleration forces, in
      particular head injury, are still the most important hazard threatening
      occupants' survival in aviation crashes. To further reduce aviation-related
      fatalities requires more effective restraint systems and other improvements in
      aircraft design.

PMID- 9290874
TI  - Sudden, unexpected death in subjects with undiagnosed gliomas.
AB  - We report two cases in which a medicolegal autopsy disclosed small and previously
      undiagnosed gliomas. The first case was a 38-year-old woman who was found dead in
      bed; her autopsy revealed a 1.3-cm low-grade astrocytoma in the right subthalamic
      area. The second case involved a 32-year-old man who drowned in shallow water
      after his canoe capsized. A 0.5-cm oligoden-droglioma of the left temporal lobe
      and a 0.1-cm ganglionic hamartoma of the hypothalamus were found. In both cases
      the tumors may, directly or indirectly, have been the underlying cause of death.
      We emphasize the importance of a thorough neuropathological examination for all
      cases of sudden unexpected death in which no extracerebral cause of death has
      been found.

PMID- 9290876
TI  - Vehicular accidents and cardiac concussion. A traumatic connection.
AB  - Concussion of the heart (commotio cordis) occurs in traffic accidents in which
      blunt force impact over the precordial area occurs, even in the absence of
      multiple blunt force injuries. The functional dynamics of the heart, with
      ventricular arrythmias and conduction disturbances, serve as the
      pathophysiological basis of this condition. As a cause of death in vehicular
      accidents, it is less common than other causes. However, it should be considered
      in the differential diagnosis, especially in cases with minor or no apparent
      injuries.

PMID- 9290875
TI  - Clinical and toxicological findings in two young siblings and autopsy findings in
      one sibling with multiple hospital admissions resulting in death. Evidence
      suggesting Munchausen syndrome by proxy.
AB  - A 15-month-old girl underwent several emergency department (ED) visits and two
      admissions for parent-reported histories of ingestions, apnea, and seizures. She
      was initially admitted following reports of several unusual episodes of syncope
      accompanied by convulsive movements and was discharged on mephobarbital with a
      diagnosis of atypical seizure disorder. The day after discharge, she was brought
      to the ED in cardiopulmonary arrest and was resuscitated after a prolonged
      period. She was declared brain dead 2 days later. Ante- and postmortem toxicology
      produced several inconclusive findings, none of which explained death. Autopsy
      findings, including neuropathology, failed to demonstrate any significant disease
      processes. Approximately 3 months later, a 4-month-old female sibling was brought
      to the ED with a parent-reported history of apnea and seizures similar to the
      deceased child. A stool specimen obtained 2 days after admission contained
      numerous tiny seeds, which were found by gas chromatography-mass spectrometry
      analysis to contain lorazepam and temazepam. The role of these benzodiazepines in
      the apnea episodes in this infant was unknown, but the presence of the seeds in
      such a young infant coupled with the parent's aberrant behavior, led to the
      tentative diagnosis of Munchausen syndrome by proxy. This diagnosis was
      strengthened when results from these studies persuaded legal authorities to
      remove the surviving sibling from the parents, resulting in an asymptomatic
      recovery.

PMID- 9290877
TI  - Homicide trends in the State of Victoria, Australia.
AB  - Limited data about homicide in Australia have been published. Data on homicide
      occurring in the state of Victoria, Australia, are presented. Since 1945 there
      has been a doubling of the population and an increase in the rate of homicide.
      The most common method of killing was shooting, and most homicide victims were
      known to their assailants. Male assailants far outnumber female assailants. Men
      are the most frequent victims, but female victims far outnumber female
      assailants. The data are compared with data on other Australian states and
      published data from other countries.

PMID- 9290879
TI  - Artifact from an electrosurgical ground pad.
AB  - Artifacts from medical intervention are frequently present in medicolegal
      autopsies and must be distinguished from injuries of forensic interest,
      particularly in deaths from trauma. In this case, burns resulting from incomplete
      skin contact of an electrosurgical ground pad during surgery for multiple gunshot
      wounds were initially confused with abrasions caused by impact of bullet
      fragments. Inspection of the decedent's clothing and of the medical records
      revealed the true etiology of this injury.

PMID- 9290878
TI  - Fatal anaphylactic reaction to hair dye.
AB  - We present the first reported case of fatal anaphylaxis resulting from the
      application of hair dye. A 68-year-old woman had a history of anaphylactic
      reaction to hair dye 2 years before her death. After using a different hair dye
      preparation, the patient experienced shortness of breath, collapsed, and died.
      Autopsy findings were consistent with anaphylaxis. Pathogenic mechanisms are
      reviewed.

PMID- 9290880
TI  - Suicide by gunshot while driving a motor vehicle. Two additional cases.
AB  - Suicide by means of a motor vehicle occurs more frequently than is generally
      realized, and may be difficult to prove. Suicide by other means while driving a
      motor vehicle is far less frequent. Only two cases of suicide by gunshot while
      driving an automobile have been previously, and recently, reported. The author
      reports two additional cases of suicide by gunshot while driving a motor vehicle.
      Each case was a young man who had been suffering from depression; who obtained a
      firearm apparently for the express purpose of committing suicide; and who shot
      himself while driving a motor vehicle on an Interstate highway. Contrary to the
      usual finding in a series of suicides, three of the four cases now reported each
      left a suicide note or notes. What is apparently a fatal single-vehicle-single
      occupant vehicular mishap may in fact be a suicide at the wheel by other means.
      What is apparently suicide by means of motor vehicle may in fact be an attempt to
      disguise homicide. Medicolegal offices are urged to routinely perform complete
      autopsies in fatal single-vehicle-single-occupant vehicular mishaps so that cause
      and manner of death may be documented without question.

PMID- 9290881
TI  - Sudden death due to butane inhalation.
AB  - Sudden death due to the inhalation of halogenated hydrocarbons is a well
      documented phenomenon in the scientific and medical literature. Recently, there
      has been sporadic information suggesting that nonhalogenated hydrocarbons may
      cause potentially fatal cardiac arrhythmias. This report documents five sudden
      deaths due to inhalation of nonhalogenated hydrocarbons: n-butane, isobutane and
      propane. The hydrocarbons were identified by headspace gas chromatography in
      blood, brain, and lung tissue. Case histories, toxicological findings and
      analytical procedures are discussed.

PMID- 9290882
TI  - Drugs in East Germany.
AB  - Germany was divided into two parts after World War II. The closed border and a
      nonconvertible currency in the Eastern part were the factors that did not allow a
      drug market to develop. Alcohol and medicaments were used as substitute drugs.
      Since Germany was reunified 5 years ago, there are now the same conditions
      prevailing for the procurement and sale of drugs in East Germany as there are in
      the Western German states. This report describes the current state of drug
      traffic, especially in Saxony, under the new social conditions.

PMID- 9290883
TI  - Oral autopsy of unidentified burned human remains. A new procedure.
AB  - Forensic dentistry plays an increasingly important role in medicolegal
      investigation and identification procedures. The oral examination may be
      difficult because of postmortem changes, especially those of carbonized corpses.
      We present a new technique of oral autopsy that includes a new means of access to
      the oral cavity designed for application on unidentified burned human remains.
      This technique preserves the facial configuration of the cadaver, allowing visual
      recognition by family members or other persons that is fundamental if the
      antemortem dental records do not exist or are not available. Also, this technique
      permits adequate work productivity by the forensic team members and can be used
      in difficult working conditions, such as mass-disaster scenarios.

PMID- 9290885
TI  - Pramipexole marketed for Parkinson's disease.

PMID- 9290884
TI  - Fatal heroin body packing.
AB  - The deaths of 10 heroin body packers are reported and contrasted to those of
      cocaine body packers. Only one was a woman, and all were traveling to or from
      Colombia. Drug packets deteriorated in the gastrointestinal tract and caused the
      deaths of eight victims. Accomplices removed drug packets from two of these
      smugglers after death occurred. One died of peritonitis stemming from a small
      bowel obstruction caused by the drug packets, and one died from the recreational
      use of heroin (nasally ingested). The heroin recovered was < or = 881 g, and the
      drug purity of the contraband in three cases was between 65% and 73%. Blood
      concentrations of morphine were < 1.0 mg/L in four victims; no morphine was
      detected in the smuggler who died of peritonitis. However, two victims had blood
      morphine concentrations of 4.4 mg/L and 6.7 mg/L, respectively, and three had
      morphine concentrations of 35.8, 39.4, and 52.6 mg/L, respectively. Fatal heroin
      body packing differs from cocaine body packing in that individuals may have
      extremely high drug levels in their blood and their accomplices appear to be more
      likely to abandon them in a remote location after attempting to remove the drug
      packets after death has occurred.

PMID- 9290888
TI  - Drug information centers pool resources.

PMID- 9290890
TI  - Computer-assisted help desk for handling drug benefits.

PMID- 9290891
TI  - An aspirin a day: advice that makes sense.

PMID- 9290892
TI  - Pharmacoeconomics of propofol in anesthesia.
AB  - Pharmacoeconomic data on the use of propofol in anesthesia are reviewed, with
      consideration of clinical characteristics that affect overall costs. Propofol is
      more expensive than many other anesthetics but its use can affect the costs of
      perioperative care as well as costs not directly related to the health care
      system, such as those associated with time off work. Using propofol can result in
      earlier discharge from the postanesthesia care unit (PACU), which can result in
      lower PACU costs. Anesthesia induction and maintenance with propofol versus
      barbiturates for induction and volatile anesthetics for maintenance have been
      associated with a lower frequency of postoperative nausea and vomiting (PONV) in
      the immediate postoperative period. A reduced frequency of PONV may improve the
      ability to increase patient flow through the PACU, which may reduce PACU costs.
      The cost of treating PONV in the PACU might not be high enough to justify the use
      of more expensive agents such as propofol solely for their reduced propensity to
      cause PONV. Propofol use has been associated with significantly shorter times to
      extubation of cardiac-surgery patients compared with the use of other agents.
      Early extubation has, in turn, been associated with shorter hospital stays,
      shorter stays in the cardiac intensive care unit, and lower hospital charges.
      Policy changes regarding criteria for discharge from the PACU may need to be
      implemented if the economic advantages of propofol are to be realized. Anesthesia
      with propofol, compared with other agents, has been associated with shorter stays
      in the PACU. Whether using propofol decreases the costs of care is unclear.

PMID- 9290893
TI  - Intra-arterial urokinase versus surgery for acute peripheral arterial occlusion.
AB  - The outcomes of intra-arterial urokinase versus surgery for acute peripheral
      arterial occlusion (PAO) were compared. Patients at a university hospital who had
      received intraarterial urokinase for PAO were identified by computer and pair
      matched on the basis of comorbidities, age, sex, and site of occlusion to
      computer-selected patients who had undergone surgery. Only patients with category
      I or II ischemia were considered. The study period for the urokinase group was
      February 1995 through January 1996, and the period for the surgery group was June
      1993 through January 1996. Twenty-eight patients in each group met the selection
      criteria. Patients who had received urokinase had a significantly shorter median
      length of stay (8.5 days) than patients in the surgery group (13 days) and
      significantly fewer infectious complications (2 versus 10). No differences in
      amputation rates, total hospital costs, or mortality rates were detected.
      Patients who received intra-arterial urokinase for PAO had a shorter length of
      stay in the hospital and fewer infectious complications than those who underwent
      surgery.

PMID- 9290894
TI  - Pharmacy-managed program for home treatment of deep vein thrombosis with
      enoxaparin.
AB  - A program for home treatment of uncomplicated acute proximal deep vein thrombosis
      (DVT) with enoxaparin is described. In fall 1995 an HMO in Southern California
      began developing a pharmacy-managed program in which selected patients with acute
      proximal DVT receive home treatment with enoxaparin. Advantages of the program
      included expected cost avoidance. The safety and efficacy of such therapy were
      verified, and quality control measures were established. Patients are referred to
      the program by the physicians making the diagnosis of proximal DVT. Upon
      referral, patients are placed in a holding area. A pharmacist orders laboratory
      tests and then prescribes warfarin and enoxaparin doses. Patients are given their
      first doses, taught to safely self-administer enoxaparin, and sent home. Follow
      up care, monitoring, and blood sampling are provided through a home health
      agency. A pharmacist monitors the International Normalized Ratio (INR) and
      telephones the patient daily to specify the day's warfarin dose. Patients receive
      concurrent enoxaparin and warfarin therapy for at least five days until the INR
      is > 2; enoxaparin is then discontinued and patients are transferred to an
      outpatient anticoagulation service for continued monitoring. From April 1, 1996,
      to March 27, 1997, 55 patients were treated under the program; all eligible
      patients were enrolled. A total of 294 hospital days were avoided. There were no
      complications or hospital admissions due to bleeding. A comprehensive program for
      home treatment of uncomplicated acute proximal DVT with enoxaparin was
      implemented at an HMO.

PMID- 9290895
TI  - Ambulatory care databases for managed care organizations.
AB  - The uses, advantages, and limitations of ambulatory care databases are discussed,
      and processes for extracting and using the data are described. Claims databases
      allow health systems, including managed care organizations, to generate
      descriptive statistics on patients, providers, and diseases; to conduct
      comprehensive cost and resource-use analyses; and to build economic models of
      diseases. The use of health care databases has several advantages over clinical
      trials, including lower data collection costs, shorter times for analysis, larger
      numbers of patients, and less inconvenience to patients and providers. These
      databases allow the effectiveness of a treatment, instead of its efficacy, to be
      assessed and drug-switching patterns within disease categories to be detected.
      This information can be used for determining the cost and outcome implications of
      new treatments and formulary changes, as well as for monitoring disease
      management programs. Limitations of health care databases include the omission of
      services not covered by health plans, the risk of coding errors, the absence of
      indicators of disease severity, and the lack of data that would assist with
      clinical outcome analysis. Medical and pharmacy claims data do not contain all
      the information contained in patients' medical records. Despite their
      limitations, ambulatory care databases are useful for describing patient,
      provider, and disease characteristics. The databases are also useful for
      predicting and estimating the implications of a change in the formulary,
      measuring the effects of treatment guidelines, and monitoring disease management
      programs.

PMID- 9290896
TI  - ASHP therapeutic position statement on the use of aspirin for prophylaxis of
      myocardial infarction.
AB  - In patients without contraindications, aspirin is an effective, low-cost, and
      relatively safe but underused option for preventing MI. Given the possible
      complications of long-term therapy, careful patient selection is warranted. ASHP
      believes that pharmacists should become actively involved in educating health
      care professionals about the benefits of using aspirin for the prophylaxis of MI
      and assisting in the identification of appropriate patients. Pharmacists should
      encourage patients to modify controllable risk factors for coronary artery
      disease (smoking, hypercholesterolemia, and hypertension) and to view aspirin as
      an adjunct, not a replacement for these efforts. ASHP strongly believes that well
      controlled clinical trials are needed to determine the benefit of aspirin
      prophylaxis of MI in women.

PMID- 9290897
TI  - Regional thrombolytic infusion for peripheral arterial occlusion and deep vein
      thrombosis: tried and true.

PMID- 9290898
TI  - Antithrombotic drugs for thromboembolic disorders: a lesson in evidence-based
      medicine.

PMID- 9290899
TI  - Low-molecular-weight heparins for treatment of deep vein thrombosis.

PMID- 9290900
TI  - Criteria for use of regional urokinase infusion for peripheral arterial
      occlusion.

PMID- 9290901
TI  - Criteria for use of regional urokinase infusion for deep vein thrombosis.

PMID- 9290902
TI  - Bulk packages of injectable products.

PMID- 9290903
TI  - Bioethics committee activities.

PMID- 9290904
TI  - Metformin, contrast media, and theophylline.

PMID- 9290906
TI  - Assessment of the acrylic resin Technovit 7200 VLC for studying the gingival
      mucosa by light and electron microscopy.
AB  - Technovit 7200 VLC is an acrylic resin formulated for embedding undecalcified
      hard tissues which are prepared for light microscopy according to a cutting
      grinding technique. To employ this resin for embedding and cutting soft tissues
      by ultramicrotomy, we carried out a qualitative study on biopsies of canine
      gingival mucosa using light and transmission electron microscopy. For a critical
      evaluation of this resin, some biopsies were embedded in Agar 100, an epoxy resin
      widely used in morphological studies. At the light microscopic level the samples
      embedded in Technovit 7200 VLC showed good morphology and excellent toluidine
      blue staining of different cell types and extra cellular matrix. At the
      ultrastructural level, nuclei, cytoplasmic organelles, collagen fibrils and
      ground substance appeared well preserved and showed high electron density. The
      acrylic resin was stable under the electron beam and its degree of shrinkage
      appeared to be very low. We conclude that Technovit 7200 VLC can be employed for
      ultramicrotomy for both light and electron microscopic investigation of soft
      tissues.

PMID- 9290905
TI  - Staining paraffin embedded sections of scald of barley before paraffin removal.
AB  - Staining of paraffin embedded sections with periodic acid-Schiff reagent and fast
      green before paraffin removal resulted in differentiation of barley seed and leaf
      tissue from fungal structures of Rhynchosporium secalis. Crystal violet,
      toluidine blue O and antiline blue also successfully stained fungal structures of
      R. secalis in barley leaf tissues. Staining of embedded sections before paraffin
      removal allows simple processing of a series of sections, saves time and reduces
      solvent consumption.

PMID- 9290907
TI  - A procedure for preparing undecalcified and unembedded bone sections for light
      microscopy.
AB  - We have developed a procedure for light microscopic investigation of
      undecalcified and unembedded bone sections. Biopsy samples of human metatarsus
      and femur and rat femur were fixed in aldehydes and sectioned with a cutting
      machine equipped with a diamond saw blade. Free sections 100-150 microns thick,
      stained with toluidine blue and von Kossa, did not show artifacts following the
      cutting, and the spatial relations of mineralized and nonmineralized components
      remained intact. Compact and trabecular bone, bone marrow and all cell types
      appeared well preserved and easily recognizable. Our procedure provides a simple
      and rapid method for preparing bone sections which undergo no chemical treatment
      other than fixation. This method is a useful alternative to standard histological
      protocols for studying bone specimens.

PMID- 9290908
TI  - Immunohistochemical differentiation of fiber types in human skeletal muscle using
      monoclonal antibodies to slow and fast isoforms of troponin I subunit.
AB  - The cDNA sequence of troponin I (TnI), one of the subunits of the skeletal muscle
      regulatory protein, differs between slow-twitch muscle and fast-twitch muscle. We
      prepared monoclonal antibodies to the slow and fast isoforms of human TnI for the
      purpose of differentiating muscle fiber types in human neuromuscular disorders.
      Slow TnI antibody was labeled with tetramethylrhodamine isothiocyanate while fast
      TnI antibody was labeled with fluorescein isothiocyanate; then these two
      antibodies were mixed. This mixture was then used to stain biopsied muscle from
      patients with neuromuscular disorders. It was possible to differentiate muscle
      fibers into slow, fast and intermediate fibers having various contents of slow
      and fast TnI. In tissue composed of small muscle fibers, this method facilitated
      differentiation of types of muscle fibers by allowing staining of only a single
      section. The usefulness of our technique using slow and fast TnI antibodies is
      discussed in comparison with ATPase staining. Because our staining method can
      distinguish slow and fast fiber components, it is useful for clinical
      application.

PMID- 9290909
TI  - Large specimen bone embedment and cement line staining.
AB  - Undecalcified embedment of large bone specimens is often challenging. A method is
      presented here that is suitable for methacrylate embedment of sections of canine
      vertebrae while retaining the ability to localize tartrate-resistant acid
      phosphatase and alkaline phosphatase activity. Specimens also retained
      tetracycline labelling, and sectioned preparations were readily stained with
      routine bone procedures. A modification of the Bodian silver stain, used for
      examining the nerves and spinal cord in these specimens, provided a useful stain
      for canaliculi and cement lines in trabecular and cortical bone. This stain is
      advantageous when both bone and nerve tissue are of interest, as in spinal fusion
      studies.

PMID- 9290910
TI  - Phospholipid containing choline histochemistry of mouse uterine epithelia during
      preimplantation stage.
AB  - The physiological role of high lipid content in endometrial cells during
      pregnancy has not been well established. In the present work we used
      histochemical techniques to analyze the total lipids and phospholipid containing
      choline (PCC) in the mouse uterine glandular and luminal epithelia during
      preimplantation stage. Sudan black histochemistry showed the highest intensity
      during the second day of pregnancy in both the basal and apical portions of
      luminal epithelium. Peaks of PCC staining were seen both in the luminal and
      glandular epithelia at the second and fifth days of pregnancy. Changes in
      localization and in the amount of lipid in the uterine epithelia suggest high
      mobility and metabolic rates of this substance, which may be related to
      morphological and/or functional changes occurring at the same time in the
      pregnant uterus. The increase and depletion timing of PCC content in the uterine
      epithelia during preimplantation stage, when uterine prostaglandin is also
      oscillating, suggest a possible involvement of PCC in prostaglandin biosynthesis.
      Therefore, the fate of lipid droplets found in the uterine epithelia may be
      related to critical changes of the pregnant endometrium, rather than the
      nourishment of developing embryos alone.

PMID- 9290911
TI  - Softening of plant specimens (Equisetaceae) to improve the preparation of
      paraffin sections.
AB  - A method is presented for softening the hard tissues of stem and strobile of
      Equisetum giganteum allowing the preparation of representative histological
      slides suitable for teaching and research. Segments of aerial portions of the
      Equisetum giganteum shoot system were fixed with formaldehyde:ethanol:acetic acid
      (5:10:5) for 24 hr at room temperature, washed in distilled water and immersed in
      a mixture of 5% hydrofluoric acid and 0.5% sulfuric acid for 1 hr at room
      temperature. Hydrofluoric acid has a higher affinity for silica components, and
      the sulfuric acid acts as a catalyst favoring the separation of calcium silcates.
      This simple, inexpensive and rapid method allows paraffin sections to be prepared
      while preserving the topographic microanatomy by decreasing technical artifacts
      produced by conventional softeners, and preserving PAS-positive polysaccharides.

PMID- 9290912
TI  - Preparation of thin sections for Fourier Transform-Infrared microscopy: a new
      embedding medium for cellulosic samples.
AB  - Fourier Transform-Infrared [FT-IR] microscopy is a combination of instrumentation
      from which information can be derived about the structure and composition of
      materials; however, it presents unique problems for sample preparation.
      Traditional methods of preparing fiber cross sections employ embedding media such
      as methacrylates, epoxides and polyvinyl alcohols, all of which have groups in
      common with the cellulose molecule, and absorb in the same regions of the IR
      spectrum. Therefore, a new embedding method employing polystyrene has been
      developed for the preparation of cross and longitudinal sections of cellulosic
      fibers. Although polystyrene is a strong IR absorbing material, it can be
      completely removed from specimens prior to analysis. In addition, FT-IR spectra
      of cross sections have better resolution than conventional preparation methods
      employing ground samples prepared in a KBr disk.

PMID- 9290913
TI  - Immunohistochemical demonstration of transferrin and transferrin receptor in
      mammalian integument.
AB  - The present study demonstrates the distribution of transferrin and the
      transferrin receptor in the integument of eleven wild mammalian species using
      immunohistochemical methods. Both substances were regularly found in or near the
      peripheral cells of the sebaceous glands, especially of dense-haired animals. The
      transferrin receptor was also detectable in the epidermis, the secretory portion
      of tubular apocrine glands, and the outer epithelium of primary hair follicles.
      Transferrin as well as the transferrin receptor reacted strongly in macrophages
      of the papillary dermis only in the common seal. The results obtained are
      discussed with regard to possible biological functions in the skin of the
      substances demonstrated.

PMID- 9290914
TI  - Health care telematics: who is liable?
AB  - This paper deals with questions of liability that may arise with the
      implementation and use of telematics and informatics in the health care sector.
      Traditionally liability has evolved around the responsible health care
      professionals. However, with increasing reliance on informatics and telematics in
      health care there may come a shift away from this concept of liability to the
      idea of shared liability between the responsible health care professionals and
      those who have provided this technology.

PMID- 9290915
TI  - The future is no longer what it used to be. Managing health telematics projects.
AB  - Future used to mean global progress and convergence of science and technology and
      society. Today, we observe the decoupling of the two poles of knowledge formation
      and application (i.e. science and technology, and culture and society,
      respectively) and also fierce confrontation between them. The key issue to
      reconcile the two poles is to re-invent the link between them. The new future
      lies in the development of mental and technical capacities for change and the
      creation of new forms of solidarity. We propose, as a general attitude, to
      reactivate and develop the four principles of efficacy-effectiveness-efficiency,
      hospitality, responsibility and pertinence. Translated into driving forces for
      the development of health care telematic projects, they amount to the acceptance
      of and capacity for enterprise-wide solutions, hospitality and capacity to
      acquire outside knowledge, self-managed, multi-functional team work spirit,
      reengineering mentality to achieve pertinent technico-cultural solutions.

PMID- 9290917
TI  - C.A.S.M. and C.A.S.T. A new information based approach to clinical audit.
AB  - This paper outlines a research project currently being conducted at the
      University of Central Lancashire. The project's aims are to develop a detailed
      structured method for clinical audit and to construct a supporting computer based
      toolset to automate the process. A discussion of the background to the research
      and an outline of the method and toolset is portrayed.

PMID- 9290916
TI  - Cognitive evaluation: how to assess the usability of information technology in
      healthcare.
AB  - As the adoption of information technology has increased, so too has the demands
      that these systems become more adapted to the physicians and nurses environments,
      to make access and management of information easier. The developers of
      information systems in Healthcare must use quality management techniques to
      ensure that their product will satisfy given requirements. This underlines the
      importance of the preliminary phase where Users Requirements are elicited. Some
      methodologies, such as KAVAS (E.M.S. Van Gennip, F. Gremy, Med. Inform. 18, 1993,
      179) chose to use a continuous assessment protocol as a key strategy for quality
      management. At each stage of the conception and development of a prototype, the
      assessment checks that it conforms to the expectation of the users' requirements.
      The methodology of evaluation is then seen as a dynamic process which is able to
      improve the design and development of a dedicated system. The purpose of this
      paper is to demonstrate the necessity to include a cognitive evaluation phase in
      the process of evaluation by: (1) evaluating the integration (usability) of the
      I.T. in the activity of the users; and (2) understanding the motives underlying
      their management of information. This will help the necessary integration of
      information management in the workload of the healthcare professionals and the
      compatibility of the prototypes with the daily activity of the users.

PMID- 9290918
TI  - The development of an approach to evaluate NHS manager's competence in medical
      informatics.
AB  - This paper describes the research and development of Checkpoint, a self
      assessment instrument. It outlines how the instrument has helped managers in the
      NHS identify their strengths and weaknesses with respect to their management and
      use of informatics. The paper presents trends and feedback from the use of
      Checkpoint and the implications for future education and training of managers in
      the NHS.

PMID- 9290919
TI  - DIAS--the diabetes advisory system: an outline of the system and the evaluation
      results obtained so far.
AB  - The present paper gives a description of the Diabetes Advisory System (DIAS), and
      the evaluation results obtained so far. DIAS is a decision support system for the
      management of insulin dependent diabetes. The core of the system is a compartment
      model of the human carbohydrate metabolism implemented as a causal probabilistic
      network (CPN or Bayesian network), which gives it the ability to handle the
      uncertainty, for example, in blood glucose measurements or physiological
      variations in glucose metabolism. The evaluation results suggest that, at least
      in our hands, DIAS can generate advice that is safe and of a quality that is at
      least comparable to what is available from experienced clinicians.

PMID- 9290920
TI  - PROforma: a general technology for clinical decision support systems.
AB  - The need for flexible and well understood knowledge representations which are
      capable of capturing clinical guidelines and protocols for decision support
      systems is widely recognised. The PROforma method for specifying clinical
      guidelines and protocols comprises a graphical notation for their design, and a
      formal knowledge representation language to enable them to be executed by a
      computer to support the management of medical procedures and clinical decision
      making. PROforma technology consists of a graphical knowledge editor for the
      creation of guidelines, and an enactment engine for testing and executing them.
      This paper provides an overview of the motivation and structure of PROforma, and
      illustrates its use in the development of clinical applications.

PMID- 9290921
TI  - A comprehensive knowledge-based system for laboratory hematology.
AB  - The Coulter FACULTY knowledge-based systems, Professor Petrushka for peripheral
      blood interpretation, Professor Fidelio for flow cytometry immunophenotyping and
      Professor Belmonte for bone marrow reporting, have been installed in several
      hospitals in Spain, Portugal and the United Kingdom. In Spain and Portugal, the
      systems are part of the IZASA-Coulter CITOTECA workstation, which includes a
      video camera for capturing microscopic images and a networkable laboratory
      information system supporting color reports. At the Royal Hospitals Trust (St.
      Bartholomew's Hospital and The Royal London Hospital, London, UK), networked
      workstations are available and the system is used daily to generate bone marrow
      reports in the hematology laboratories. There have been considerable benefits
      from adopting Coulter FACULTY for bone marrow reporting, including faster
      turnaround time, improved quality of the reports and cost savings.

PMID- 9290922
TI  - An asynchronous co-operative model for co-ordinating medical unit activities.
AB  - CSCW is devoted to the analysis of interactions among human beings when
      performing their work together (Ellis et al., Commun. ACM 1 (34) (1991) 38-58).
      The main fields of application are work organisation, healthcare, education and
      training. Our main goal is to study the co-operative models allowing task co
      ordination and conflict management between actors within a distributed
      environment, particularly in medical units. We do not aim to produce a practical
      system suitable for near-term deployment in the intensive care units (ICU), but
      rather an experimental system that performs and co-ordinates a range of
      intelligent planning tasks in ICU activities. The emphasis will be put especially
      on asynchronous co-operation. We apply the Workflow approach to ICU organisation
      through the analysis and the proposal of a co-operative model.

PMID- 9290923
TI  - Can we solve current problems with nursing information systems?
AB  - Dutch nurses are confronted with health care information systems quite often.
      However, they do not take full advantage of electronic support for their care
      activities and professional development. The nursing process is often considered
      the core of nursing care delivery and guides the documentation of care.
      Currently, this process can be supported electronically. However, the actual use
      of nursing information systems (NISs) in the Netherlands is limited to a few
      sites. Therefore, it is timely to analyse the problems that exist in the
      development and use of NISs and to look for solutions to solve them. This paper
      proposes both the nursing information reference model (NIRM), and structured
      discussions for a proper course of action in the development and use of NISs.

PMID- 9290924
TI  - Building healthcare delivery and management systems centred on information about
      the human aspects.
AB  - The importance of modern information systems to manage healthcare delivery at the
      macro level--particularly through purchasing--is increasingly being recognised.
      There is also increasing investment in electronic patient record systems to aid
      care delivery. Both are intended to benefit the individual, yet neither gives
      full consideration to the human aspects and values--largely because of the under
      development of appropriate terms and structures. It is important to identify and
      structure the human facets as the determinants and principal components of
      healthcare delivery systems, to improve the information structure of these
      components, and then to use them as the building blocks of macro-management
      systems, so as to fuel the whole dynamic with one set of person-based values.

PMID- 9290925
TI  - A strategy for empowerment: the role of midwives in computer systems
      implementation.
AB  - The procurement and implementation of patient administration systems has been
      done on numerous occasions in the past. The Rotunda project however encompassed
      major bespoke clinical developments which were going to impact upon large
      clusters of midwives, and medical staff to a lesser extent. A broad based four
      level structured methodology was used to implement the project which is
      significantly ahead of schedule. This methodology together with its strengths and
      weaknesses is comprehensively discussed. The empowerment of midwives, their roles
      in systems analysis and design, software testing and organisational re
      engineering is described. The importance of undertaking comprehensive computer
      training is highlighted and a compact 10 h information technology course coupled
      with ongoing educational and related activities which could be adopted by any
      organisation is documented. The seven deadly sins of project management are
      mapped out. An update on benefits realisation is provided. Gender issues are also
      discussed.

PMID- 9290926
TI  - Automatic SNOMED classification--a corpus-based method.
AB  - This paper presents a method of automatic classification of clinical narrative
      through text comparison. A diagnosis report can be classified by searching
      archive texts that show a high textual similarity, and the 'nearest neighbor
      classifies the case. This paper describes the method's theoretical background and
      gives implementation details. Large scale simulation experiments were run with a
      wide range of histology reports. Results showed that for 80-84% of the trials,
      relevant classification lines were included among the first five alternatives. In
      5% of the cases, retrieval was unsuccessful due to the absence of relevant
      archive reports. From the results it is concluded that the method is a versatile
      approach for finding potentially good classifications.

PMID- 9290927
TI  - Health services, coordination and the Internet.
AB  - The on-going specialization of medical services requires socioeconomic
      coordination of different health services. The GP is the key to improve this
      primary coordination. To qualify referral decisions by the GP an Internet-like
      information system (VisInfo) has been implemented in Denmark. This VisInfo
      contains information on (1) alternative periods of waiting, (2) medical
      guidelines for specific treatments (3) clinical home pages, and (4) links to non
      medical providers of health services (NGOs). VisInfo was originally implemented
      in the Counties of Funen, Northern Jutland and Vejle in 1993-1995. A number of
      other counties are implementing similar information systems whereof the County of
      Frederiksborg, recently has implemented the first real Internet-system.
      Provisional experiences with the VisInfo strategy is presented on (1) the general
      user interest, (2) elaborations of the strategy, and (3) organization. Based on
      the BlackSeaDiab Action Plan and the BlackSea TeleDiab project, the potential for
      dissemination of medical informatics in the Black Sea Region through an adaption
      of the VisInfo strategy is discussed.

PMID- 9290928
TI  - Experiences with the german teleradiology system MEDICUS.
AB  - This paper introduces the teleradiology system, MEDICUS, which has been developed
      at the Deutsches Krebsforschungszentrum (German Cancer Research Center) in
      Heidelberg, Germany. The system is designed to work on ISDN lines as well as in a
      local area network. The global software architecture is explained in the article.
      Special attention has been given to the design of the user interface and data
      security, integrity and authentication. The software has been evaluated in a
      German field test at 13 radiology departments in university clinics, small
      hospitals, private practices and research institutes. More than 30 thousand
      images have been transmitted using this system during a 9 month period. Realized
      application scenarios are: in-house communication, image and report delivery to
      referring hospitals, remote reporting, radiotherapy treatment planning and
      research cooperation. Experience has shown that the system is easy to use and
      saves time. It obviates the need for patient transport and reduces film costs.
      Experiences of individuals while using the system during the field test helped
      define the functionality of the second generation teleradiology system which is
      even more flexible and is also available as a commercial product.

PMID- 9290929
TI  - Systolic hypertension in the elderly.

PMID- 9290930
TI  - Jaap Dubbeldam: professor of neurobehavioural morphology.

PMID- 9290931
TI  - Pigeon basal ganglia: insights into the neuroanatomy underlying telencephalic
      sensorimotor processes in birds.
AB  - This paper reviews the organization of the avian and mammalian striatum. The
      striatum receives input from virtually the entire rostrocaudal and mediolateral
      expanse of the cerebral cortex. The corticostriatal projections appear to be
      glutamatergic, forming excitatory synapses in the striatum. Another major
      projection to the avian striatum that also appears to be glutamatergic stems from
      a set of nuclei in the dorsal zone of the avian thalamus that are comparable to
      the mammalian intralaminar, mediodorsal, and midline nuclei. Furthermore, the
      striatum receives a massive projection from dopaminergic neurons of the ventral
      tegmental area and substantia nigra in the midbrain tegmentum. In return, the
      midbrain tegmentum receives a direct GABAergic/substance P-ergic/ dynorphinergic
      projection from the striatum, as well as an indirect one formed by
      GABAergic/substance P-ergic/ dynorphinergic and GABA-ergic/enkephalinergic
      striatal neurons projecting to the pallidum in the first step, and pallidal
      GABAergic/LANT6/parvalbumin neurons projecting to the midbrain tegmentum in the
      second step. In addition to its projection neurons, the striatum possesses
      GABAergic and cholinergic interneurons. One motor output pathway of the striatum
      runs via the pallidum and dorsal thalamic ventral tier nulei to the motor cortex.
      In addition to this pathway, birds possess a major descending pathway from the
      basal ganglia to the tectum via the GABAergic nucleus spiriformis lateralis in
      the pretectum. On hodological and topological grounds, similar nuclei, although
      not GABAergic, can be found in mammals. Finally, an other striatal motor output
      is formed by a sequential GABAergic pathway from the basal ganglia via the
      substantia nigra to the tectum. In conclusion, it appears that the organization
      of the avian and mammalian basal ganglia is similar rather than different.

PMID- 9290932
TI  - Sensory representation in the cerebellum and control circuits of motion.
AB  - The role of the cerebellum in motion and posture control as deduced from the
      behaviorial effects of lesions has long been known. Subsequent recording and
      tracing studies in mammals yielded a cerebellar sensory representation featuring
      'animalculi', not unlike those seen in the cerebral cortex. This image of
      cerebellar representation had to be revised with the demonstration of the
      'fractured somatotopy' in somatosensory projections (Welker, 1987). A point in
      case is the trigeminal representation in the mammalian cerebellum, which still
      lacks a functional explanation. While a fractured somatotopy--if present--has yet
      to be demonstrated in birds, the topographical details of the trigeminal
      representation appear to vary considerably between and within both classes. This
      undoubtedly reflects the variety of functions trigeminocerebellar links subserve
      in the two classes, but is also indicative of species-specific cerebellar output
      variation. In this context the importance of cerebellar afferent topography for
      cerebellar function is discussed.

PMID- 9290934
TI  - Behavioral morphology of the pigeon's peck: ingestion, prehension and cognition.
AB  - In nature, pecking involves the transport of a prehensile effector organ (the
      beak) towards biologically significant targets, and the generation jaw movement
      patterns whose probability and topography are appropriate to the stimulus
      properties of the target (e.g., distance, direction, size) and the motivational
      state of the animals (hunger, thirst). Because conditioned pecking preserves
      essential topographic features of the ingestive peck, we have used the pigeon's
      conditioned pecking response as a "model system" for the study of motor control,
      response form modulation and cognitive processes. In the first study,
      conditioning procedures were used to bring pecking under the control of visual
      targets whose stimulus properties (size, location) were independently varied,
      while simultaneously monitoring head acceleration, jaw movements and terminal
      peck location. Comparison of the kinematic profiles of conditioned and ingestive
      pecks suggests that conditioned pecking is functionally analogous to human
      "pointing" rather than "grasping" behavior. In the second study, we manipulated
      reinforcer type and size to generate populations of "virtual" eating and drinking
      responses and used them to study the process of response form modulation. The
      data suggest that different response forms do not reflect "fixed" movement
      patterns but the modulation of movement patterns across a topographic continuum.
      In the third study we manipulated stimulus, response and deprivational variables
      to test a cognitive model for the study of "expectancy", "intention", and
      "choice" in pigeon.

PMID- 9290933
TI  - On the structure and function of the tectofugal visual pathway in laterally eyed
      birds.
AB  - Of the two visual systems in vertebrates, the tectofugal pathway has often been
      attributed to stimulus localization, while the thalamofugal pathway was thought
      to be involved in stimulus identification. This review provides evidence that the
      tectofugal pathway serves both functions. It is speculated that the initial task
      of the tectum is to localize an object and to guide the fixation movement. The
      object in focus is then analysed by the higher stations of the tectofugal system.
      The result of the analysis is fed into the optic tectum and is used for decision
      about the treatment of the object.

PMID- 9290935
TI  - Visual sensation during pecking in pigeons.
AB  - During the final down-thrust of a pigeon's head, the eyes are closed gradually, a
      response that was thought to block visual input. This phase of pecking was
      therefore assumed to be under feed-forward control exclusively. Analysis of high
      resolution video-recordings showed that visual information collected during the
      down-thrust of the head could be used for 'on-line' modulations of pecks in
      progress. We thus concluded that the final down-thrust of the head is not
      exclusively controlled by feed-forward mechanisms but also by visual feedback
      components. We could further establish that as a rule the eyes are never closed
      completely but instead the eyelids form a slit which leaves a part of the pupil
      uncovered. The width of the slit between the pigeon' eyelids is highly sensitive
      to both, ambient luminance and the visual background against which seeds are
      offered. It was concluded that eyelid slits increase the focal depth of retinal
      images at extreme near-field viewing-conditions. Applying pharmacological methods
      we could confirm that pupil size and eyelid slit width are controlled through
      conjoint neuronal mechanisms. This shared neuronal network is particularly
      sensitive to drugs that affect dopamine receptors.

PMID- 9290936
TI  - Separate channels for visuomotor transformations in the pigeon.
AB  - Since the discovery of two parallel visual systems in humans and primates there
      has been much speculation about their functions. One prominent current model,
      suggesting independent processing of visual information for perception and
      action, is supported by neuroanatomical, electrophysiological, neurobehavioral,
      and human clinical data. Furthermore, studies of visuomotor behavior in
      amphibians and non-primate mammals indicate that neural processing of action
      related behavior is mediated by separate neuronal channels thus suggesting an
      evolutionary principle in the organization of visuomotor behavior. If such an
      evolutionary principle operates it should also apply to birds. I will present and
      discuss behavioral and behavioral physiological evidence that action-related
      behavior in pigeons like pecking, grasping and control of gaze is controlled via
      separate neuronal channels subserving visuomotor functions.

PMID- 9290937
TI  - Visual lateralization in birds: from neurotrophins to cognition?
AB  - Birds which are tested monocularly in visual discrimination tasks generally show
      higher performance levels with the right eye seeing. Due to the virtual complete
      decussation of the optic nerves, a right eye superiority is probably related to a
      left hemisphere dominance. If visual processes between the hemispheres differ,
      each half-brain might be differently prone to be deceived by visual illusions.
      Indeed pigeons tested with the herringbone illusions are deceived to a stronger
      extent with the right eye. These functional asymmetries are accompanied by
      anatomical left-right differences in the ascending thalamo- and tectofugal visual
      pathways in chicks and pigeons, respectively. The neuroanatomical and behavioral
      assymmetries result from an asymmetrical posture before hatching in which the
      embryo keeps his head turned to the right, such that the right eye is stimulated
      by light shining through the shell. The lateralization of adult animals are
      induced by this prehatching asymmetric photic stimulation since dark incubation
      abolishes behavioral and anatomical asymmetries. It is conceivable that the
      asymmetrical embryonal light stimulation increases the release of neurotrophins
      in the developing avian visual system in an activity dependent matter.
      Neurotrophins play an important role in neuronal survival and morphology and thus
      might represent a molecular switch bridging the gap from embryonal light
      stimulation to asymmetries of visual cognition in adults.

PMID- 9290938
TI  - Functional anatomy of neural pathways contributing to the control of song
      production in birds.
AB  - In birds, as in humans, vocal control involves the intricate coordination of
      three major groups of muscles, namely, those of the vocal organ, the respiratory
      apparatus, and the vocal tract, including the jaw and tongue. The neural pathways
      involved in the control of each of these groups of muscles are described for
      songbirds and compared with those in non-oscine birds and mammals. The pathway in
      songbirds that controls the syrinx, the bird's vocal organ, originates in the
      telencephalon and projects via the occipito-mesencephalic tract directly upon
      vocal motoneurons in the medulla. Activity in this pathway configures the syrinx
      into phonatory positions for the production of species typical vocalizations.
      Another component of this pathway mediates control of respiration during
      vocalization, since it projects upon both expiratory and inspiratory groups of
      premotor neurons in the ventrolateral medulla, as well as upon several other
      nuclei en route. This pathway appears to be primarily involved with the control
      of the temporal pattern of song, but is also importantly involved in the control
      of vocal intensity, mediated via air sac pressure. There are extensive
      interconnections between the vocal and respiratory pathways, especially at
      brainstem levels, and it may be these that ensure the necessary temporal
      coordination of syringeal and respiratory activity. The pathway mediating control
      of the jaw appears to be different from those mediating control of the syrinx and
      respiratory muscles. It originates in a different part of the telencephalon and
      projects upon premotor neurons in the medulla that, on preliminary analysis,
      appear to be separate from those projecting upon the syringeal motor nucleus. The
      separateness of this pathway may reflect the imperfect correlation of jaw
      movements with the dynamic and acoustic features of song. The brainstem pathways
      mediating control of vocalization and respiration in songbirds have distinct
      similarities to those in non-oscine birds and in mammals such as cats and
      monkeys. However, songbirds and parrots, like humans, but unlike other non
      songbirds, have developed a special telencephalic vocal control system for the
      production of learned vocalizations.

PMID- 9290939
TI  - Effect of phenothiazines on activated macrophage-induced luminol-dependent
      chemiluminescence.
AB  - The inhibitory effect of some phenothiazine neuroleptics (chlorpromazine,
      levomepromazine, thioridazine, promethazine and trifluoperazine) on the ability
      of rat peritoneal macrophages to produce O2- during phagocytosis was
      investigated. The superoxide radical release was estimated by measuring the
      luminol-dependent chemiluminescence (CL). The effect of drugs was studied in the
      concentration range of 0.1-100 mumol/l. Additional experiments to determine the
      ability of the drugs to scavenge O2- were carried out. They included measuring
      the effect of phenothiazines on the luminol-dependent CL in systems with
      enzymatically (xanthine-xanthine oxidase) and non-enzymatically (KO2) generated
      O2-. The ability of phenothiazines to scavenge O2- was additionally tested by a
      "non-luminescence" method in which the superoxide concentration was determined
      spectrophotometrically by the reduction of nitro blue tetrazolium to formazan.
      All drugs tested decreased significantly CL of stimulated macrophages at
      concentrations greater than 1 mumol/l. The C50 values were between 0.45 and 1.74
      mumol/l. Also phenothiazines were found to act as scavengers of O2-. However,
      this effect occurred at significantly higher drug concentrations. The C50 values
      for 50% scavenging of O2- in systems with different sources of O2- were in the
      concentration range of 5-160 mumol/l. These results suggested that phenothiazines
      predominantly affected the ability of macrophages to produce O2- during
      phagocytosis. The findings may provide some insight into the untoward effects of
      the drugs tested.

PMID- 9290940
TI  - Fluorescence energy transfer on erythrocyte membranes.
AB  - Stationary and time-dependent fluorescence were measured for a donor/ acceptor
      (DA) pair bound to membrane proteins of bovine erythrocyte ghosts. The donor N-(p
      (2-benzoxazolyl)phenyl)-maleimide (BMI) and the acceptor fluram bind to SH- and
      NH2-residues, respectively. The fluorescence spectra and the time-dependent
      emission were consistent with radiationless fluorescence energy transfer (RET).
      Band3 protein is the only membrane spanning protein with accessible SH-groups for
      the coupling of BMI molecules, and therefore only acceptor binding sites on the
      same band3 protein were counted by the RET measurements performed. A density of
      RET-effective acceptor binding sites c = 0.072 nm-2 was calculated on the basis
      of the two-dimensional Forster-kinetics.

PMID- 9290941
TI  - Computer simulation of excitation-contraction coupling in cardiac muscle. A study
      of the regulatory role of calcium binding to troponin C.
AB  - The influence of a change of troponin concentration as well of a change of
      binding and dissociation of Ca2+ ions to the regulatory protein troponin C on the
      time course of isometric tension has been studied, using a mathematical model
      developed to investigate excitation-contraction coupling in cardiac muscle cells.
      The numerical simulations show that peak amplitude, rate of force development,
      time to peak tension and relaxation time depend significantly on the above
      parameters even in the case when the equilibrium dissociation constant remains
      unchanged. The obtained results might be useful for the planing of new
      experiments in the view of the fact that no similar data have been reported for
      cardiac muscle cells as yet.

PMID- 9290943
TI  - Two components of potassium outward current in smooth muscle cells from the
      circular layer of human jejunum.
AB  - Two components of the outward K+ currents (Ik) of cells isolated from the
      circular layer of human jejunum were investigated using the conventional whole
      cell voltage clamp method. A fast transient Ik component could only be elicited
      by depolarization in cells dialysed with pipette solution of pCa < 7.4. This Ik
      component was strongly voltage dependent, and could be selectively abolished by
      30 mumol/l quinidine. Its amplitudes decreased in the absence of Ca entry, the
      decrease depending on the duration of cell exposure to media containing calcium
      blockers, and disappeared after depletion of intracellular Ca2+ stores. The
      steady-state component of Ik was sensitive to tetraethylammonium. This component
      had comparable amplitudes at pCa = 8.4 or pCa = 7.4 of the pipette solution, and
      was present during a long-lasting exposure of cells to solutions containing
      Ca(2+)-blocking drugs.

PMID- 9290942
TI  - Diethylpyrocarbonate, a histidine selective reagent, causes structural alteration
      of rat ovarian LH/hCG receptor.
AB  - Treatment of rat ovarian membrane-bound and Triton X-100 solubilized LH/hCG
      receptor with a histidine-specific reagent diethylpyrocarbonate (DEPC) resulted
      in inactivation of the ability of the receptor to bind hCG. The partial
      reversibility of this inhibition by hydroxylamine demonstrated that histidine
      residues are involved in hCG-receptor binding. Fluorescence quenching experiments
      indicated that DEPC did not change the accessibility of fluorophores for
      acrylamide. Alterations of quenching rate generally suggest exposure of
      tryptophanyl residues. Modification of histidyl residues was connected with an
      alteration of the physical state of ovarian membranes. Membrane lipid rigidity
      was decreased after DEPC reaction. Thermal perturbation techniques were used to
      monitor structural changes in the receptor due to the action of DEPC on
      membranes. Heat inactivation of hCG-binding sites demonstrated that there was a
      significant destabilization of the LH/hCG receptor structure when the membranes
      were treated with DEPC. Thermal destabilization produced by 5 mmol/l DEPC caused
      a decrease in T50 values by about 12 degrees C. These results suggest that
      histidine residues are located at the binding sites of the receptor, and that
      they are also involved in alterations of membrane proteins, the structural
      integrity of which secondarily influences the accessibility of the LH/hCG
      receptor.

PMID- 9290944
TI  - Triadic Ca2+ modulates charge movement in skeletal muscle.
AB  - The effects of intracellular Ca2+ changes on charge movement in frog skeletal
      muscle were investigated using high concentrations (10-20 mmol/l) of buffers with
      different abilities to buffer Ca2+ at distances close to the SR Ca2+ release
      channels. In BAPTA compared with EGTA perfused fibers, charge movement was
      attenuated and lacked the characteristic kinetic features (I beta and I gamma) of
      E-C coupling charge movements. Qmax decreased by 9 nC/microF, Vmid was shifted 1
      6 mV to more negative potentials, and the steepness factor increased by 3-5 mV.
      Results of varying the holding potential suggested that BAPTA decreases the
      amount of charge available to move upon depolarization. Raising intracellular
      Ca2+ to micromolar levels at a fixed BAPTA concentration prevented the decline in
      Qmax, suggesting that intracellular Ca2+ can modulate the amount of charge that
      is in the resting or available state. The different results obtained with BAPTA
      and EGTA can be explained by the greater ability of BAPTA to buffer dynamic Ca2+
      changes at distances close to the release sites. These results are consistent
      with the proposals that an intracellular Ca2+ site on or near the dihydropyridine
      receptor, termed here the 'availability site', modulates the amount of charge
      available to move upon depolarization and is normally populated by Ca2+ released
      into the triad junction during activity.

PMID- 9290946
TI  - Ferrous-ascorbate complexes as carriers of nitric oxide.
AB  - Ferrous-ascorbate is known to form with nitric oxide paramagnetic nitrosyl
      ferrous-ascorbate complexes, Fe-AA-NO. These complexes yield on EPR signal with g
      factor close to 2.02 and an optical absorption spectrum with maxima at 340, 460,
      and 600 nm. Fe-AA-NO complexes are unstable in the presence of oxygen. Ferrous
      ascorbate complexes promote NaNO2 decay resulting in the formation of NO. Nitric
      oxide is taken up by Fe-AA complexes to form paramagnetic ferrous-ascorbate
      nitrosyl complexes, Fe-AA-NO. It is suggested that ferrous-ascorbate complexes
      can play the role of carriers of NO and, perhaps, O2 in the blood plasma.
      Nitrosyl ferrous-ascorbate complexes can also be the NO containing factor
      involved in the blood vessel relaxation (endothelium-derived relaxing factor,
      EDRF).

PMID- 9290945
TI  - Stimulation-dependent redistribution of charge movement between unavailable and
      available states.
AB  - A previous study (Stroffekova and Heiny 1997) demonstrated that changes in
      resting, intracellular free Ca2+ can modulate the amount of charge which is
      available to move upon depolarization and do excitation-contraction-coupling (E-C
      coupling). Charge movement reflects voltage-driven conformational changes of the
      dihydropyridine receptor which couple membrane excitation to Ca2+ release from
      the sarcoplasmic reticulum (SR) and contractile activation (c.f. review: Melzer
      et al. 1995). The present study demonstrates that dynamic changes in free Ca2+
      that occur in the triadic gap during SR Ca2+ release can likewise produce a
      stimulation-dependent increase in the amount of available charge. Thus this
      modulation occurs in the physiological range of Ca2+ changes that occur in the
      triad during normal muscle activity. The modulation of charge movement by
      intracellular Ca2+ was rapid and maintained; it occurred within 2-3
      suprathreshold depolarizations and remained for 5-10 minutes. It could be
      prevented by intracellular BAPTA and by depleting the SR of Ca2+, but not by EGTA
      or agents known to alter ion channel phosphorylation. These results are explained
      by a model in which a Ca2+ binding site on or near the voltage-sensor is normally
      populated by Ca2+ ions released into the triadic junction during activity and
      modulates the distribution of voltage sensors between available and unavailable
      states.

PMID- 9290947
TI  - Immunoglobulin/Myc recombinations in murine Peyer's patch follicles.
AB  - Immunoglobulin heavy chain (Igh)/Myc recombinations are a hallmark of pristane
      induced mouse plasmacytomas but are also frequently found in non-tumorous
      tissues. Here we describe for the first time a PCR-based technique for detecting
      fusions between Igh mu or Igh alpha and Myc in situ. Igh/Myc recombinations were
      found in transplanted and primary plasmacytomas. In addition, the gut-associated
      lymphoid tissues of plasmacytoma-free BALB/c mice were investigated for the
      presence of Igh/Myc fusions. Igh/Myc rearrangements were detected in Peyer's
      patch follicles and in the intestinal lamina propria both in normal mice and in
      mice shortly after pristane treatment. The sequence analysis showed that i) three
      to five different Igh/Myc hybrid sequences were present in individual follicles,
      ii) Igh/Myc recombinations can be subjected to additional switch recombinations
      as shown by related sequences in neighboring cells, and iii) cells harboring
      these rearrangements migrate into the adjacent lamina propria. The results
      indicate that Peyer's patches are a hyper-recombinogenic tissue. Myc
      recombination-positive cells are present in at least 100-fold more frequently
      than expected if recombinations were random, which suggests that this kind of
      trans-chromosomal rearrangement may be targeted.

PMID- 9290948
TI  - FHIT gene and the FRA3B region are not involved in the genetics of renal cell
      carcinomas.
AB  - The FHIT gene locus at 3p14.2 covers about 500 kb, including the fragile site
      FRA3B and the constitutional t(3;8) breakpoint associated with the development of
      multiple renal cell carcinomas (RCC). A terminal deletion of the short arm of
      chromosome 3 with the most distal breakpoint in the FRA3B region is the
      characteristic genetic event in nonpapillary RCC. Since aberrant FHIT transcripts
      have been observed in gastrointestinal and other tumors, this gene has been
      suggested to function as a tumor suppressor. To evaluate the role of FHIT and the
      FRA3B region in the genetics of RCC, we analyzed FHIT expression by RT-PCR and
      performed microsatellite deletion mapping in the FHIT region. In addition to two
      cases from a t(3;8) family, only three out of 100 sporadic nonpapillary RCC
      showed a breakpoint within the FHIT region, whereas 94 tumors showed a deletion
      breakpoint proximal to the FHIT gene. FHIT transcripts of normal size were
      observed in 33 out of 34 tumors. Direct sequencing of eight PCR products revealed
      a normal FHIT sequence without mutations in the coding region. An established
      cell line from a renal cancer xenograft showed a smaller FHIT transcript.
      Sequence analysis revealed a mixture of several splicing variants of the FHIT
      gene. Since only three out of 100 sporadic nonpapillary RCC had a deletion
      breakpoint within the FRA3B/FHIT region, and since all but one renal cell tumor
      showed a normal FHIT transcript, we can exclude the involvement of the FHIT gene
      and the FRA3B region in the genetics of renal cell cancer.

PMID- 9290949
TI  - Precise localization of the FHIT gene to the common fragile site at 3p14.2
      (FRA3B) and characterization of homozygous deletions within FRA3B that affect
      FHIT transcription in tumor cell lines.
AB  - Chromosomal or allelic losses at 3p14 are common in a variety of human tumors,
      including those of the lung, breast, kidney, and head and neck. This suggests the
      existence of a tumor suppressor gene in this band. A promising candidate is the
      recently cloned FHIT gene, which spans the common fragile site, FRA3B, at 3p14.2.
      We previously identified a region of fragility at 3p14.2 (FRA3B) of > 85 kb by
      cloning DNA flanking pSV2neo integrations and constructed a partial genomic
      contig of the region. Using probes from the contig, we tested for deletions
      within this region in DNA from 105 human tumor cell lines, predominantly derived
      from lung cancers. We identified one gastric and four lung cancer cell lines with
      homozygous interstitial deletions involving the FRA3B region. The deletion in one
      lung cancer cell line lies entirely within our contig and is < 65 kb. We have
      identified, cloned, and sequenced this breakpoint junction. We have also shown
      that our probes lie within intron S of the FHIT gene and, furthermore, that exon
      5 is located approximately 1 kb from one of our probes and, thus, lies within the
      region of fragility. Two lines with entirely intronic deletions yield FHIT
      transcripts of normal size. In one of these, this was the sole transcript
      identified. In the other line, an FHIT transcript completely normal in sequence
      was accompanied by two larger abnormal transcripts. These results leave open the
      possibility that some homozygous deletions within the FHIT gene are without
      phenotypic effect and result from genetic instability of this region. However,
      taken together, our results provide evidence that breakage and rearrangement
      within the FRA3B fragile site sequences result in alterations of FHIT and are
      likely to be involved in carcinogenesis.

PMID- 9290950
TI  - Absence of TP53 alterations in pheochromocytomas and medullary thyroid
      carcinomas.
AB  - The role of the TP53 gene in the development of inherited and sporadic
      pheochromocytomas and medullary thyroid carcinomas (MTC) has not been clarified
      because of conflicting reports and limitations in the assays used to detect
      mutations. To determine the frequency of TP53 alterations in these tumors, 22
      pheochromocytomas and 29 MTCs were screened for loss of heterozygosity (LOH) on
      17p with four markers. Single-strand-conformation-variant (SSCV) analysis of
      exons 4-9 of the TP53 gene was performed in 20 of the pheochromocytomas and in 22
      of the MTCs. The expression of p53 was determined by immunohistochemistry in 19
      pheochromocytomas and in 17 MTCs using two antibodies (D01 and D07) on frozen and
      paraffin-embedded tissues. Four of the 22 pheochromocytomas and none of the MTCs
      showed LOH on 17p. No mutations were detected in any of the tumors screened by
      SSCV analysis. Immunohistochemical staining of frozen and paraffin-embedded tumor
      sections did not show p53 overexpression in any of the tumors examined. Our
      findings indicate that mutations in the TP53 gene are an uncommon event in the
      tumorigenesis of pheochromocytomas and medullary thyroid carcinomas.

PMID- 9290952
TI  - 17q12-21 amplicon, a novel recurrent genetic change in intestinal type of gastric
      carcinoma: a comparative genomic hybridization study.
AB  - We studied DNA copy number changes in gastric cancer (GC) using comparative
      genomic hybridization (CGH) analysis on 35 resected gastric carcinomas (22 of the
      intestinal type and 13 of the diffuse type). Eighty-three percent of the cases
      showed DNA copy number changes. Gains were more common than losses (median of 3
      and 1 in primary tumors of the intestinal and diffuse type, respectively). The
      most common gains were detected on 20q [46%; 12 intestinal type (55%) and four
      diffuse type (31%)], 8q [37%; 10 intestinal type (45%) and three diffuse type
      (23%)], and 17q12-21 [29%; all but one intestinal type (41%)]. The most frequent
      losses were detected on 18q [26%; all intestinal type (41%)] and on 4q [23%; all
      intestinal type (32%)]. High-level amplifications were observed in the intestinal
      type of tumors at 17q12-21 (three tumors), 20q (three tumors). 2q (one tumor),
      and 18q (one tumor). In the diffuse type, high-level amplification was detected
      once at 13q.

PMID- 9290951
TI  - Molecular cytogenetic analysis of a nontumorigenic human breast epithelial cell
      line that eventually turns tumorigenic: validation of an analytical approach
      combining karyotyping, comparative genomic hybridization, chromosome painting,
      and single-locus fluorescence in situ hybridization.
AB  - The immortalized, nontumorigenic human breast epithelial cell line HMT-3522 has
      been used as a model for premalignant and, eventually, malignant development.
      During cultivation, the karyotype evolution was followed. At an early stage, a
      very long constant phase showed a near-diploid karyotype, with only five marker
      chromosomes. DNA from this phase was used for comparative genomic hybridization
      (CGH) analysis, confirming a previously known MYC amplification, and the
      integration sites were subsequently determined by single-locus fluorescence in
      situ hybridization (FISH). Furthermore, gains of 5q22-qter and 20q11-qter and
      deletion of most of chromosome 6 (6p23-qter) were detected by CGH. Because of
      uncertainty about some of the indicated changes, including a deletion of Ip35
      pter, the CGH findings were investigated more closely by chromosome painting,
      leading to a revision of the karyotype: 45,XX,del(I)(p35),-6,dup(8)(pter-
      >qter::qter-->q24),der(12) t(6;12)(p23;
      p13),der(14)t(5;14)(q22;q32.3),der(17)t(8;17;20)(17pter-->17q25 ::8qter-->
      8q23::8q24-->8qter::8q24-->8qter:: 8q23-->8q24.1::20q11-->20qter). Some
      karyotypic changes were confirmed by CGH; others had to be revised; and, in the
      Ip35 region, classical cytogenetics seems superior to CGH. However, CGH revealed
      a karyotypically unsuspected dup(20q) that might be of special relevance to
      breast tumor initiation or progression. Our study confirms that CGH is
      supplementary to current technologies, e.g., karyotyping and Southern analysis,
      but cannot replace them. In addition, our cell line turned out to be an excellent
      model for comparison among the different methods. The results imply that future
      cytogenetic analyses of complex karyotypes should be based on a combination of
      karyotyping, CGH, and FISH.

PMID- 9290953
TI  - The effect of different TP53 mutations on the chromosomal stability of a human
      colonic adenoma derived cell line with endogenous wild type TP53 activity, before
      and after DNA damage.
AB  - We examined the effect of loss of wild type TP53 activity on the chromosomal
      stability of a human colonic adenoma derived cell line (designated AA/Cl) by
      studying transfected variants which express different TP53 mutations. Using gross
      chromosomal aberrations as a measure of instability, we studied metaphase spreads
      of a vector control cell line (AA/PCMV) and variants expressing the 143(Val-Ala)
      mutation, which retain endogenous wild type TP53 activity, or the 273(Arg-His)
      TP53 mutation, which acts as a dominant negative. It was found that the
      proportion of cells with more than 4% aberrations was significantly greater in
      the AA/273p53/B cell line (an approximate 5-Fold increase) than in the vector
      control or the AA/143p53/A cell line. To investigate whether loss of TP53
      dependent checkpoints also predisposed the cells to accumulate persistent
      chromosomal aberrations after DNA damage, cells were exposed to 5 Gy gamma
      radiation. Regardless of TP53 status, cells with radiation induced chromosomal
      damage were eliminated through a TP53 independent mechanism, suggesting that loss
      of TP53 activity did not permit the survival of these cells. In contrast, when
      exposed to low level gamma radiation (0.2 Gy), decreased wild type TP53 function
      and/or expression of mutant TP53 protein led to increased radioresistance (both
      in the non-dominant as well as the dominant mutant expressing cell lines). These
      findings suggest that loss of TP53 activity and/or acquisition of specific TP53
      mutations can increase chromosomal instability and resistance to low level DNA
      damage in human colonic adenoma cells. This study emphasises the different
      biological consequences of individual TP53 mutations on the genotype of
      premalignant colorectal epithelial cells and subsequent implications for
      tumorigenic progression.

PMID- 9290954
TI  - Analysis of the BRCA1 and BRCA2 genes in sporadic meningiomas.
AB  - Several lines of evidence suggest a relationship between the occurrence of
      meningiomas and that of breast carcinomas: Both occur more frequently in women
      than in men, and a higher incidence of meningiomas has been observed in patients
      with a history of breast carcinoma. Both tumor types also express receptors that
      are associated with a proliferative response to progesterone, estrogen, and
      androgen hormones. Despite this clinical evidence, no genetic links between the
      two tumor types have been found. The breast carcinoma genes BRCA1 and BRCA2 have
      been linked to familial and sporadic forms of breast cancer and ovarian cancer,
      providing an opportunity to test this clinical observation. We conducted studies
      to detect alterations of the BRCA genes in meningiomas. Evaluation of 60 sporadic
      meningiomas with a panel of eight microsatellite and two restriction fragment
      length polymorphism markers at the locations of BRCA1 and BRCA2 demonstrated no
      loss of heterozygosity. Microsatellite instability was detected for one
      meningioma at two markers close to the BRCA2 locus. Northern blot analysis did
      not reveal any differences in mRNA expression of meningiomas compared to control
      tissues. These results suggest that alterations of the BRCA1 and BRCA2 genes are
      not common pathogenetic events in the development of sporadic meningiomas.

PMID- 9290955
TI  - Novel MLL-CBP fusion transcript in therapy-related chronic myelomonocytic
      leukemia with a t(11;16)(q23;p13) chromosome translocation.
AB  - CBP, which is located on 16p13 and encodes a transcriptional adaptor/coactivator
      protein, has been shown to fuse by the t(8;16)(p11;p13) translocation to MOZ on
      8p11 in acute myeloid leukemia. We found a t(11;16)(q23;p13) in a child with
      therapy-related chronic myelomonocytic leukemia. Subsequent reverse transcriptase
      polymerase chain reaction and direct sequencing analyses revealed the MLL-CBP
      fusion transcript in CMML cells. Because 11q23 translocations involving MLL and
      t(8;16) involving MOZ and CBP have been reported in therapy-related leukemias,
      both the MLL and CBP genes may be targets for topoisomerase II inhibitors.
      Accordingly, we believe that most t(11;16)-associated leukemias may develop in
      patients who have been treated with cytotoxic chemotherapy for primary malignant
      diseases.

PMID- 9290957
TI  - Cytogenetic, fluorescence in situ hybridisation, and clinical evaluation of
      translocations with concomitant deletion at 13q14 in chronic lymphocytic
      leukaemia.
AB  - Deletions and translocations of 13q14 are the most frequent structural chromosome
      abnormalities found in chronic lymphocytic leukaemia (CLL). We have identified
      13q14 translocations in the blood of 30 of 450 (6.6%) CLL patients by
      conventional cytogenetics, using tetradecanoyl phorbol 12-myristate 13-acetate
      (TPA) as a mitogen. The translocations are characterised by multiple partner
      chromosomes and a high incidence, 6 of 30 cases, of complex rearrangements. Seven
      cases were also studied by fluorescence in situ hybridisation (FISH) using four
      previously ordered YACs, to define the breakpoints further. Deletions with
      varying proximal and distal breakpoints were found in six cases. Two of the cases
      had deletions of the cytogenetically normal chromosome 13 at q14, and in one case
      the 13q14 translocation was a secondary genetic event. No difference in the
      clinical features between the patients with 13q14 translocation and 54 patients
      with 13q14 deletions or four patients with both a translocation and a deletion
      was observed. These data suggest that the genetic consequence of 13q14
      translocations in CLL is the loss of a tumour suppressor gene.

PMID- 9290958
TI  - Codeletion of the JUN proto-oncogene and the CDKN2A tumor-suppressor gene in HRAS
      transformed rat embryo fibroblast cell lines.
AB  - The cyclin kinase inhibitor p16, encoded by the CDKN2A gene, suppresses the
      transformation of mouse embryonic fibroblasts by oncogenic RAS. In contrast, the
      c-JUN transcription factor (a major component of AP-1) has been suggested to be
      required for RAS transformation of rodent fibroblasts. The CDKN2A gene and the
      JUN proto-oncogene have both been mapped to rat chromosome band 5q31-33. We here
      show that both copies of the CDKN2A gene are deleted in four of eight transformed
      cell lines derived from the transfection of rat embryo fibroblasts (REF) with
      HRASVAL12. In two cell lines, the homozygous deletions involved a larger area on
      5q31-33, which included the JUN proto-oncogene. JUN-defective cells showed high
      AP-1 binding activity. Both AP-1 binding activity and stromelysin (transin) mRNA
      expression were found to be RAS-dependent in one of the JUN-defective cell lines.
      The finding of deletions of the CDKN2A gene in RAS-transformed REF cell lines is
      consistent with the concept that CDKN2A suppresses transformation by RAS. The
      occasional concomitant loss of the adjacent JUN proto-oncogene does not prevent
      establishment of transformed and tumorigenic cell lines.

PMID- 9290956
TI  - BCL3 rearrangements and t(14;19) in chronic lymphocytic leukemia and other B-cell
      malignancies: a molecular and cytogenetic study.
AB  - The t(14;19)(q32.3;q13.1) is a recurring translocation found in the neoplastic
      cells of some patients with chronic lymphocytic leukemia (CLL) or other B
      lymphocytic neoplasms. We previously cloned the translocation breakpoint
      junctions present in the leukemic cells from three such patients and identified a
      gene, BCL3, whose transcription is increased as a result of the translocation. In
      the present paper, we describe three additional patients with the t(14;19), one
      with lymphoma and two with CLL, and report the cloning and sequencing of the
      breakpoint junction in one of these patients as well as in a previously reported
      patient. We and others have found that the breakpoints on chromosome 14, with one
      exception, fall within the switch region upstream of the immunoglobulin heavy
      chain C alpha 1 or C alpha 2 sequences. Several of the breaks within chromosome
      19 fall immediately upstream of the BCL3 gene, but several others are more than
      16 kb 5' of the gene. Most patients with CLL and the t(14;19) also show trisomy
      12.

PMID- 9290959
TI  - Hamartoma of the breast with involvement of 6p21 and rearrangement of HMGIY.
AB  - The first description of involvement of 6p21 and rearrangement of HMGIY in a
      hamartoma of the breast is in keeping with the emerging role of HMG genes in
      benign mesenchymal tumors.

PMID- 9290960
TI  - Loss of heterozygosity of chromosome 13 in Merkel cell carcinoma.
AB  - We have examined a series of 24 Merkel cell carcinoma (MCC) DNAs for loss of
      heterozygosity (LOH) at eight loci on chromosome 13. All patients were
      heterozygous for at least one locus. Overall, 18 of 24 (75%) patients showed LOH,
      among whom 10 patients demonstrated LOH at all informative loci. A single common
      region of loss was identified in all cases and included the marker D13S233
      (13q14.3), which maps close to the retinoblastoma susceptibility gene RB1. The
      RB1 protein was not detected by Western blot analysis in any of nine MCC cell
      lines tested. These data indicate that 13q losses are the most common chromosomal
      losses observed to date in MCC and the likely target of these deletions is the
      RB1 locus.

PMID- 9290961
TI  - Analysis of the fragile histidine triad gene in primary gastric carcinomas and
      gastric carcinoma cell lines.
AB  - The FHIT (fragile histidine triad) gene has been isolated from the chromosome
      region 3p14.2, which includes the fragile site locus FRA3B and the breakpoint of
      the t(3;8) of familial renal carcinoma. FHIT has been suggested to be a candidate
      tumor suppressor gene for digestive tract carcinomas. To evaluate the
      significance of FHIT gene abnormalities in gastric carcinogenesis, we examined
      the allelic status and transcripts of the gene in 23 primary gastric carcinomas
      as well as 7 gastric carcinoma cell lines. Four of the seven (57%) cell lines
      exhibited homozygous deletions of variable sizes at 3p14.2 all of which included
      D3S1300, which is located close to, or within, FRA3B. However, only 2 of 16 (13%)
      informative cases showed loss of heterozygosity at D3S1300 in the primary tumors.
      Direct analysis by reverse transcriptase polymerase chain reaction failed to
      reveal abnormal transcripts, including exon skipping and sequence changes, in the
      primary tumors or in the cell lines without homozygous deletions. These results
      suggest that FHIT gene abnormalities are infrequent in primary gastric carcinomas
      and that the frequent homozygous deletions seen in cell lines might simply
      reflect the plasticity of the genome at FRA3B under culture conditions.

PMID- 9290962
TI  - Whither short-course chemotherapy for leprosy?

PMID- 9290963
TI  - Efficacy of single dose multidrug therapy for the treatment of single-lesion
      paucibacillary leprosy. Single-lesion Multicentre Trial Group.
AB  - A multicentre double-blind controlled clinical trial was carried out to compare
      the efficacy of a combination of rifampicin 600 mg plus ofloxacin 400 mg plus
      minocycline 100 mg (ROM) administered as single dose with that of the standard
      six-month WHO/MDT/PB regimen. The subjects included 1483 cases with one skin
      lesion who were previously untreated, were smear-negative, and had no evidence of
      peripheral nerve trunk involvement, and they were randomly divided into study and
      control groups. The total duration of the study from the day of intake was 18
      months, and 1381 patients completed study. Only 12 patients were categorized as
      treatment failure and no difference was observed between the two regimens.
      Occurrence of mild side-effects and leprosy reactions were minimal (less than 1%)
      in both groups. This study showed that ROM is almost as effective as the standard
      WHO/MDT/PB in the treatment of single lesion PB leprosy.

PMID- 9290964
TI  - Delayed resolution versus treatment failure in paucibacillary leprosy patients
      under six months fixed duration multidrug therapy.
AB  - Thirty paucibacillary (PB) patients were given multidrug therapy (MDT) PB regimen
      for six months and were examined clinically and histopathologically before
      therapy, at six months and 12 months after therapy; and in four patients, at 18
      to 23 months after MDT. Histopathological activity was present in 50% and 25% of
      patients after six months and 12 months respectively after MDT. At 18 to 23
      months, the four patients continued to have active lesions both clinically and
      histopathologically. On the basis of this study it is found that fixed duration
      of MDT is effective in a large majority of patients especially those with
      indeterminate leprosy. However, there is "delayed resolution" in a significant
      number of patients which in a few instances may turn out to be "treatment
      failures". Therefore, a regular follow up of high risk patients for at least two
      years and if possible, five years, with freedom to intervene with additional anti
      inflammatory or antileprosy therapy as desired, is recommended.

PMID- 9290965
TI  - Peripheral nerve abscess in leprosy: report of twenty cases.
AB  - During the year 1994-1995, 20 of the 67 leprosy patients attending the
      dermatology department with any kind of nerve involvement were found to be having
      nerve abscess. These abscesses occurred in all types of leprosy (except the
      Indeterminate) and a variety of nerve trunks and cutaneous nerves. In none of the
      instances the abscess was associated with reaction. All the patients were
      surgically treated, without any steroid therapy. All cases showed significant
      improvement whenever there was nerve function deficit. Similarly, pain was
      relieved in all cases, when it was present.

PMID- 9290967
TI  - Patterns of indoor admissions of leprosy patients in pre-MDT and post-MDT era and
      a role for leprosy referral hospital in leprosy integration programme.
AB  - Analysis of the admission patterns in a leprosy referral hospital during the last
      27 years (1966 through 1993) shows a decrease in the number of annual admissions
      since 1987. While there were 1550 admissions during 1981-1983, only 842 patients
      were admitted during 1991-1993. There was no great change in the reasons for
      admission, about 46% for reactions, 37% for ulcers, 5% for neuritis and about 12%
      for other problems. However, compared to the pre-MDT days, admissions for
      neuritis have increased. A case is made for the continuation of special leprosy
      referral hospital even beyond the year 2000 AD, i.e., even after elimination of
      leprosy as a public health problem.

PMID- 9290966
TI  - Protective sensibility--its monofilament nylon threshold equivalents in leprosy
      patients.
AB  - An attempt has been made to definite the levels of "protective sensibility" in
      terms of perception thresholds to monofilament nylon induced touch/pressure
      stimuli. Certain problems were observed while interpreting the observations.
      There appears to be a range of threshold values instead of a clear cut-off point.
      We suggest that a monofilament nylon stimulus two times the normal threshold
      value for that patient be taken as cut-off point. This will make the observations
      of Birke and Sims (1986) and Hammond and Klenerman (1987) reasonable without
      having any need to exclude the cases who defy the boundaries laid by them. Since
      the genesis of plantar ulcer is multifactorial, it appears logical to include all
      patients who have a certain degree of hypoaesthesia, for special ulcer care
      program. The likely problems while using monofilament nylons in the field and
      their possible solutions have also been outlined.

PMID- 9290968
TI  - Hidden sources of infection in unapproachable areas.
AB  - The population living in the hilly terrains of Panvel taluka, District Raigad of
      Maharashtra State was examined in a special campaign carried out during a time
      when the majority of the population will be stationed at the hills. Examination
      of 10499 persons revealed 108 leprosy cases (PR 10.3/1000) of which 72 were
      paucibacillary (PB) and 29 were multibacillary (MB) cases. Among the PB cases,
      only two had single lesion type and among the 29 MB cases, 14 were smear
      positive, having BI more than 4. These untreated advanced leprosy cases, in view
      of their frequent migrations in order to earn their livelihood, may be
      responsible for transmitting the infection in the plains areas where multidrug
      therapy is practiced since 1990. In order to achieve early leprosy elimination,
      it is necessary to cover populations in difficult areas like the one mentioned by
      special action programmes.

PMID- 9290969
TI  - Mycobacterium leprae: biochemical studies of clinical relevance.

PMID- 9290970
TI  - Characterization of leprosy based on the nasal lipid profile.
AB  - While extracting the M. leprae from the nasal flushings of leprosy patients it
      was found that these organisms were trapped in the waxy layer, between the
      aqueous and the chloroform layers. Thin layer chromotography (TLC) analysis of
      this layer, using chloroform-methanol-water system, revealed different spots when
      sprayed with acid alcohol and heated at 160 degrees C. The TLC profile of lipids
      of lepromatous and borderline (MB according to the WHO terminology) leprosy
      patients was distinctly different from that of tuberculoid leprosy patients and
      normal human volunteers. A simple, economical and fast procedure to characterize
      patients belonging to different spectra has been developed.

PMID- 9290971
TI  - Tuberculoid leprosy--one phenomenon with many perceptions.

PMID- 9290972
TI  - Development of foot-drop after recovery from chickenpox.

PMID- 9290973
TI  - Primary hyperpigmented palmar lesion: a rare presentation of borderline
      tuberculoid leprosy.

PMID- 9290974
TI  - Referrals of smear-positive leprosy cases at an urban centre.

PMID- 9290975
TI  - Follow-up of smear-positive cases treated with dapsone monotherapy.

PMID- 9290976
TI  - Bacteriological status of newly registered leprosy cases in the last decade at an
      urban centre in Mumbai.

PMID- 9290977
TI  - Enlarged great auricular nerves in a case of neurofibromatosis.

PMID- 9290979
TI  - Preparation of thymectomized irradiated (T900r) mice: a modification.

PMID- 9290978
TI  - Pattern of leprosy in children in Jodhpur.

PMID- 9290980
TI  - Workshop on "Control Of Leprosy and Tuberculosis in Urban Set Up", September 21,
      1995, Bombay.

PMID- 9290982
TI  - II International Conference on the Elimination of Leprosy, New Delhi, 11-13
      October 1996.

PMID- 9290981
TI  - Seminar on "New Dimensions in Rehabilitation of Persons with Leprosy (Community
      Based Rehabilitation)", December 6, 1995, Bombay.

PMID- 9290983
TI  - Dobutamine and the oxygen uptake/supply relationship in sepsis: from global to
      regional--nothing is simple and easy.

PMID- 9290984
TI  - Anti-inflammatory therapies: application of molecular biology techniques in
      intensive care medicine.

PMID- 9290985
TI  - The effect of dobutamine infusion on splanchnic blood flow and oxygen transport
      in patients with acute pancreatitis.
AB  - OBJECTIVES: To measure the blood flow distribution and oxygen transport in
      pancreatitis and to evaluate the regional effects of increased systemic blood
      flow. DESIGN: Nonrandomized controlled trial. SETTING: A general intensive care
      unit in a tertiary care center. PATIENTS: 10 patients with pancreatitis requiring
      mechanical ventilation were studied after fluid resuscitation, and for the
      response to dobutamine, the patients served as their own controls. For the
      baseline, 11 patients scheduled for elective abdominal surgery served as a
      control group. INTERVENTIONS: Systemic and regional hemodynamics were measured
      after fluid resuscitation to predefined hemodynamic endpoints. In patients with
      pancreatitis, the measurement was repeated after cardiac output had been
      increased by at least 25% by dobutamine. MEASUREMENTS AND RESULTS:
      Hepatosplanchnic blood flow was estimated using regional catheterization and the
      dye dilution method. In patients with pancreatitis, the cardiac index did not
      differ from that of the control group (3.9 +/- 0.8 vs 4.1 +/- 0.71.min-1.m-2;NS).
      Accordingly, there was no difference in the splanchnic blood flow (1.1 +/- 0.4 vs
      1.2 +/- 0.51.min-1.m-2;NS). Systemic and splanchnic oxygen consumption was
      increased in patients with pancreatitis (179 +/- 25 vs 147 +/- 27 ml.min-1.m-2, p
      < 0.05 and 68 +/- 15 vs 49 +/- 19 ml.min-1.m-2, p < 0.05), and systemic and
      splanchnic oxygen extraction was higher (0.34 +/- 0.08 vs 23 +/- 0.05, p < 0.01
      and 0.46 +/- 0.18 vs 0.28 +/- 0.08, p < 0.05, respectively). Dobutamine had
      inconsistent effects on splanchnic blood flow: in individual patients, splanchnic
      blood flow even decreased substantially. CONCLUSIONS: In severe pancreatitis,
      oxygen consumption is increased in the splanchnic region; increased splanchnic
      oxygen demand is not always met by adequately increased blood flow. Increasing
      the systemic blood flow with dobutamine does not improve perfusion in the
      splanchnic bed.

PMID- 9290986
TI  - Effect of sucralfate on gastric intramucosal pH in critically ill patients.
AB  - OBJECTIVE: To determine whether sucralfate administration affects the tonometric
      measurement of gastric intramucosal pH (pHi). DESIGN: Non-randomized
      observational study. SETTING: General intensive care unit of a teaching hospital.
      PATIENTS: Twenty critically ill, mechanically ventilated, consecutively admitted
      patients requiring an arterial catheter and nasogastric tube. INTERVENTIONS:
      Tonometer placement and sucralfate administration. MEASUREMENTS AND MAIN RESULTS:
      We simultaneously determined tonometer saline PCO2 (PCO2i), arterial blood gases,
      pH of gastric juice and pHi. These parameters were evaluated immediately before
      sucralfate administration, and 2 h and 4 h after. We did not detect any change in
      either PCO2i or pHi after sucralfate administration (PCO2i: basal 6.4 +/- 1.7, 2
      h 6.3 +/- 1.7, 4 h 6.3 +/- 1.7; pHi: basal 7.35 +/- 0.13, 2 h 7.36 +/- 0.12, 4 h
      7.36 +/- 0.12). CONCLUSIONS: Sucralfate does not affect the tonometric
      measurement of PCO2i and pHi.

PMID- 9290987
TI  - A controlled study of leukocyte activation in septic patients.
AB  - OBJECTIVE: Qualitative and quantitative evaluation of leukocyte activation in
      septic patients in comparison to two control groups. DESIGN: A prospective
      clinical study in which the leukocyte oxidative output of whole blood was
      measured in three groups of patients. Two chemiluminescence markers (luminol or
      lucigenin), indicative of either total oxidant output or superoxide production,
      and three stimuli (opsonized zymosan, formyl-methionyl-leucyl-phenylalanine
      (fMLP), phorbol myristate acetate) (PMA), representing different pathways of
      leukocyte activation, were used. Tumor necrosis factor, interleukin-6 and C
      reactive protein (TNF, IL-6, and CRP) were determined to evaluate the severity of
      the inflammatory process. SETTING: Intensive care and surgical units of a
      university hospital. PATIENTS: Seventy-four healthy patients, ten ICU patients
      without signs of sepsis or systemic inflammatory response syndrome and 19 septic
      patients were studied. MEASUREMENT AND MAIN RESULTS: With all three stimuli,
      whole blood total oxidative output and superoxide production were generally
      increased in septic patients. This was most likely due to the increased leukocyte
      numbers in these patients. When the chemiluminescence values were normalized per
      phagocyte (granulocytes and monocytes), the total oxidative output of septic
      phagocytes decreased with opsonin and fMLP but increased with PMA, while
      superoxide output decreased regardless of the stimuli used. TNF, IL-6 and CRP,
      although increased in septic patients as compared to ICU controls, correlated
      weakly with oxidant output. CONCLUSIONS: The oxidative output of whole blood was
      increased in septic patients compared to controls because of elevated leukocyte
      numbers. However, oxidant output normalized for phagocyte numbers generally
      decreases during sepsis for most stimuli. Cytokines and CRP do not appear to be
      associated with the extent of oxidant output during sepsis.

PMID- 9290988
TI  - The value of lumbar puncture in the evaluation of critically ill, non
      immunosuppressed, surgical patients: a retrospective analysis of 70 cases.
AB  - OBJECTIVE: To evaluate the diagnostic value of lumbar puncture (LP) in surgical
      intensive care unit (SICU) patients. DESIGN: Retrospective chart review. SETTING:
      Surgical intensive care unit at a major tertiary care medical center. PATIENTS:
      All patients admitted to the SICU during the period 1987-1995 who had a lumbar
      puncture, excluding those with a history of recent head trauma or a neurosurgical
      procedure. MEASUREMENTS: Cerebral spinal fluid (CSF) results, indication for
      lumbar puncture; admitting service, length of ICU stay, presence of fever and use
      of antibiotics. RESULTS: Of 7,555 admissions to the SICU over the period 1987
      1995, 204 patients underwent LP during the hospital admission. Four charts could
      not be located and 75 patients underwent LP in locations other than the SICU. Of
      the remaining 125 cases, 55 carried a neurosurgical diagnosis and 70 had non
      neurosurgical problems. Fifty-three (75%) of the patients had received
      antibiotics prior to the procedure. Among the 70 cases without a primary
      neurosurgical diagnosis, LP was performed to rule out infective meningitis
      suggested by fever and mental status changes (30 patients), mental status changes
      alone (7 patients), systemic illness with fever and/or mental status changes (10
      patients), seizures (10 patients), meningismus (+/- fever, 4 patients), or a
      combination of neurological findings (8 patients). There were no cases in which
      meningitis was positively diagnosed. Medical management was altered in only two
      patients based upon the results obtained by LP. CONCLUSIONS: We conclude that LP
      in SICU patients without a recent history of head trauma or a neurosurgical
      operation is a low yield procedure, especially for the diagnosis of bacterial
      meningitis.

PMID- 9290989
TI  - Measurement of cardiac output by transesophageal echocardiography in mechanically
      ventilated patients. Comparison with thermodilution.
AB  - OBJECTIVE: The determination of basal cardiac output (CO) and of its variations
      during different therapeutic interventions liable to increase or decrease it in
      mechanically ventilated patients using transesophageal echocardiography (TEE).
      DESIGN: To compare CO measurements simultaneously obtained by transmitral single
      plane TEE and thermodilution. SETTING: Medical intensive care unit. PATIENTS:
      Twenty-two consecutive mechanically ventilated patients hospitalized for various
      medical conditions were included. INTERVENTIONS: The comparisons between
      transmitral single-plane TEE and thermodilution measurements were made at
      baseline and after different therapeutic interventions affecting CO (fluids or
      dobutamine infusion or positive end-expiratory pressure titration). MEASUREMENTS:
      Seventy-four measurements were obtained. Cardiac output using TEE was the product
      of the mitral valve area, the time-velocity integral of flow at the same site and
      the heart rate. RESULTS: A significant correlation was observed between
      thermodilution and TEE measurements of CO (n = 74, r = 0.78, p < 0.001) despite
      wide limits of agreement (mean +/- 2SD = -0.3 +/- 3.1 l/min). Thermodilution and
      TEE CO determinations both had significant inverse correlation with the arterial
      venous oxygen content difference in ten consecutive patients (r = 0.77, p < 0.01
      and r = 0.71, p < 0.01, respectively). The correlation between variations of CO
      greater than 20% obtained by thermodilution and TEE was significant (r = 0.89, p
      < 0.001). The operative characteristics implied the ability of TEE to predict
      significant variations of thermodilution CO (sensitivity 85% and negative
      predictive values 86%). Moreover, arterial-venous oxygen content difference
      changes of 5% or more were better detected using TEE than thermodilution.
      CONCLUSIONS: These results suggest that although transesophageal CO measurements
      cannot replace thermodilution ones, the determination of CO variations obtained
      using TEE may be useful in the management of critically ill mechanically
      ventilated patients. This technique may make it possible to monitor hemodynamics
      during initial therapeutic interventions in those patients in whom right heart
      catheterization cannot be performed immediately.

PMID- 9290990
TI  - Nine equivalents of nursing manpower use score (NEMS).
AB  - OBJECTIVES: To develop a simplified Therapeutic Intervention Scoring System
      (TISS) based on the TISS-28 items and to validate the new score in an independent
      database. DESIGN: Retrospective statistical analysis of a database and a
      prospective multicentre study. SETTING: Development in the database of the
      Foundation for Research on Intensive Care in Europe with external validation in
      64 intensive care units (ICUs) of 11 European countries. MEASUREMENTS AND
      RESULTS: Development of NEMS on a random sample of TISS-28 items, cross
      validation on another random sample of TISS-28, and external validation of NEMS
      in comparison with TISS-28 scored by two independent raters on the day of the
      visit to the ICUs participating in an international study. Multivariable
      regression techniques, Pearson's correlation, and paired sample t-tests were used
      (significance at p < 0.05 level). Intraclass correlation, rate of agreement, and
      kappa statistics were used for interrater reliability tests. The TISS-28 items
      were reduced to NEMS (9 items) in a random sample of 2000 records; the means of
      the two scores were no different: TISS-28 26.23 +/- 10.38, NEMS 26.19 +/- 9.12,
      NS. Cross-validation in a random sample of 996 records; mean TISS-28 26.13 +/-
      10.38, NEMS 26.17 +/- 9.38, NS; R2 = 0.76. External validation on 369 pairs of
      TISS-28 and NEMS has shown that the means of the two scores were no different:
      TISS-28 27.56 +/- 11.03, NEMS 27.02 +/- 8.98, NS; R2 = 0.59. Reliability tests
      have shown an "almost perfect" interrater correlation. Similar to studies
      correlating TISS with Simplified Acute Physiology Score (SAPS)-I and/or Acute
      Physiology and Chronic Health Evaluation II scores, the value of NEMS scored on
      the first day accounts for 30.4% of the variation of SAPS-II score. CONCLUSIONS:
      NEMS is a suitable therapeutic index to measure nursing workload at the ICU
      level. The use of NEMS is indicated for: (a) multicentre ICU studies; (b)
      management purposes in the general (macro) evaluation and comparison of workload
      at the ICU level; (c) the prediction of workload and planning of nursing staff
      allocation at the individual patient level.

PMID- 9290991
TI  - Out of hospital outcome and quality of life in survivors of combined acute
      multiple organ and renal failure treated with continuous venovenous
      hemofiltration/hemodiafiltration.
AB  - OBJECTIVE: To study the out-of-hospital quality of life and long-term survival of
      critically ill patients with combined multiple organ failure and acute renal
      failure treated with continuous renal replacement therapy (CRRT). DESIGN: Study
      based on responses to postal questionnaire and clinical information obtained
      during treatment in the intensive care unit (ICU). SETTING: ICUs of two tertiary
      institutions. PATIENTS: 85 survivors from a pool of 250 patients with combined
      acute multiple organ and renal failure who were treated with CRRT. METHOD AND
      RESULTS: Anonymous postal questionnaire based on an activity index, mental
      function index, and a simplified version of the Nottingham Health Profile. Of the
      250 patients, 85 (34%) survived to be discharged from hospital: 57 males (67%)
      and 28 females (33%), mean age 56.9 years (range 13.4-81). Mean duration of ICU
      stay was 10.9 days (range 2-52), mean admission Acute Physiology and Chronic
      Health Evaluation II score was 24.2 (range 15-41), and mean duration of CRRT was
      6.2 days (range 1-34). Mean follow-up time was 2.5 years (range 0.1-5.3). Thirty
      three of the 85 patients (38.8%) did not reply to the questionnaire; 35 patients
      (41.7%) were alive at the time of response and 17 (20%) were deceased. Of the 35
      responders, 68.5% were satisfied with their present state of health, despite
      60.6% stating that their mobility had been affected, with 41.9% being unable to
      walk more than 200 metres. Most (94.5%) survivors, however, felt that their
      treatment had been worthwhile, and 91.2% said that they would undergo the same
      treatment again if necessary. The approximate cost for each year of survival was
      U.S. $ 50000. CONCLUSIONS: In the majority of patients who survived to be
      discharged from hospital after combined acute multiple organ and renal failure,
      the overall state of health and quality of life seemed acceptable. Most patients
      felt that their treatment was worthwhile and that they would undergo the same
      treatment again if necessary. Our findings suggest that the cost and effort
      associated with CRRT and ICU care in these patients are high but broadly
      comparable to those associated with the care of other serious illnesses. They are
      also seen as worthwhile by survivors, who consider their life to be of acceptable
      quality.

PMID- 9290992
TI  - Inhaled nitric oxide in newborn and paediatric patients with pulmonary
      hypertension and moderate to severe impaired oxygenation: effects of doses of 3
      100 parts per million.
AB  - OBJECTIVE: To assess the effects of inhaled nitric oxide (INO) 3-100 ppm on
      oxygenation in both newborn and paediatric patients with pulmonary hypertension
      and impaired gas exchange. DESIGN: Open, prospective, multicentre study. SETTING:
      Tertiary neonatal and paediatric intensive care units in university referral
      centres. PATIENTS: Newborn (age < or = 7 days; n = 26) and paediatric (age 8 days
      7 years; n = 16) patients with pulmonary hypertension verified by
      echocardiography and an oxygenation index of (OI) 15-40 were included in the
      study. INTERVENTIONS: The patients were subjected to stepwise increases in doses
      of INO (0, 3, 10, 30, 60, 100 ppm). MEASUREMENTS AND RESULTS: The effect on
      oxygenation was measured by repeated blood gas analysis. A positive response to
      INO was defined as a reduction in OI of > or = 25% compared to baseline (0 ppm).
      INO was found to improve oxygenation in both newborn (p < 0.0001) and paediatric
      (p = 0.015) patients and the response rate was 77 and 50%, respectively. A marked
      interindividual difference in the magnitude of the response was found between
      patients (change in OI compared to baseline: -90 to 15%). Only 2 of 28 responding
      patients required doses in excess of 30 ppm in order to show a positive response.
      CONCLUSIONS: INO is capable of improving oxygenation in both newborn and
      paediatric patients with pulmonary hypertension and impaired gas exchange,
      although the magnitude of the individual response can vary greatly. Doses in
      excess of 30 ppm are only rarely required in order to achieve a reduction in the
      oxygenation index of > or = 25%.

PMID- 9290993
TI  - Acute colonic pseudoobstruction (Ogilvie's syndrome) in two patients receiving
      high dose clonidine for delirium tremens.
AB  - We describe two cases of severe colonic pseudo-obstruction (Ogilvie's Syndrome)
      after high dose clonidine i.v. infusions for delirium tremens. The first symptoms
      occurred 36 h and 5 days, respectively, after institution of therapy. The
      diagnosis of colonic pseudo-obstruction (CPO) was confirmed during emergency
      laparotomy in both cases. While other known risk factors may have been present,
      we propose that clonidine had a major parasympatholytic effect on the large bowel
      of these patients and was therefore responsible, either alone or in combination
      with these other factors, for the development of CPO. We conclude that the
      therapy of delirium tremens with high i.v. doses of clonidine carries the risk of
      provoking severe CPO, especially when other contributing factors are present.
      While therapy of the alcohol withdrawal syndrome with clonidine appears to be an
      attractive alternative to conventional treatment, ICU physicians should be
      alerted to this potentially serious complication.

PMID- 9290994
TI  - Systemic inflammatory response syndrome in intravascular lymphomatosis.
AB  - Intravascular lymphomatosis (IVL) is characterized by an intravascular
      proliferation of atypical mononuclear cells of haematopoietic origin occluding
      small blood vessels including venules, capillaries and small arteries, and can
      affect virtually any organ in the body. Clinically, the most common
      manifestations are involvement of the skin and central nervous system, although
      various organ involvement has been described. We report a patient who presented
      with fever and rash, and succumbed with acute neurological symptoms and systemic
      inflammatory response syndrome (SIRS) with no evidence of infection. The
      postmortem revealed disseminated involvement of virtually every organ with IVL,
      the malignant cells being of T-cell origin, which may secrete cytokines including
      tumour necrosis factor and interleukin-1, that are believed to be mediators in
      SIRS. In the absence of evidence of infection on microbiology and pathology, we
      postulate that the features of SIRS in this patient was due to the disseminated
      malignancy itself.

PMID- 9290995
TI  - Acute respiratory distress syndrome due to falciparum malaria in a pregnant
      woman.
AB  - We report the case of a pregnant woman (29th week), living in a Paris suburb,
      about 20 miles from an international airport. She presented with septic shock and
      severe acute respiratory distress syndrome (ARDS). A few parasitized erythrocytes
      were discovered in a hemorrhagic bronchoalveolar lavage (BAL), specimen and many
      were found on examination of the placenta after a caesarean section had been
      performed. The patient's condition dramatically improved once given quinine
      therapy. This is an uncommon case on account of: (1) the unusual clinical course
      with no organ failure but ARDS, (2) the unusual way the diagnosis was made, (3)
      the very unusual way the patient became contaminated (airport malaria), (4) the
      pregnant condition of the patient.

PMID- 9290997
TI  - Angioedema: the role of ACE inhibitors and factors associated with poor clinical
      outcome.
AB  - OBJECTIVE: We sought to study the prevalence of angiotensin-converting enzyme
      (ACE) inhibitors, a cause of angioedema, and investigate any association between
      clinical findings at the time of presentation and clinical outcome. DESIGN AND
      SETTING: Retrospective review of the charts of all patients presenting with
      angioedema to the emergency department at our tertiary referral teaching hospital
      or clinics over a 4-year period. The charts were reviewed for documentation of
      chief complaint(s), physical findings, medical treatment, need for laryngoscopy
      and/or endotracheal intubation, triage, and probable etiology. RESULTS: Of the 40
      patients presenting with angioedema in this study, 15 cases were caused by ACE
      inhibitors. They were the most common cause of angioedema, accounting for 38% of
      all cases. The incidence of ACE inhibitor-induced angioedema is estimated to be
      0.14%. More patients with angioedema secondary to ACE inhibitors had complaints
      of odynophagia (p < 0.02), whereas only patients with non-ACE inhibitor causes of
      angioedema presented with pruritus (p < 0.02). Furthermore, patients presenting
      with an acute reaction within 24 h of exposure to the causative agent were more
      likely to require inpatient monitoring (p < 0.05). Both odynophagia and edema of
      the tongue were significant predictors for undergoing laryngoscopy (p < 0.001 and
      p < 0.02, respectively) and admission to the hospital (p < 0.05). CONCLUSION: ACE
      inhibitors are the number one cause of acute angioedema in this tertiary referral
      teaching hospital. Odynophagia and tongue swelling at the time of presentation
      had significant implications for diagnostic intervention and admission to the
      hospital.

PMID- 9290998
TI  - Time to reassess the term "base excess" for negative acid-base balance.

PMID- 9290996
TI  - Esophageal obstruction by solidification of the enteral feed: a complication to
      be prevented.
AB  - We report three cases of esophageal obstruction due to solidification of enteral
      feed refluxed from the stomach in patients being fed through a nasogastric tube.
      All three patients were administered sucralfate continuously by tube. The few
      previous descriptions of this rare complication have also implicated sucralfate
      with its pathogenesis. Given its clinical importance and the growing use of long
      term enteral nutrition, this adverse event needs to be considered.

PMID- 9290999
TI  - Esophageal intubation and mechanical ventilation.

PMID- 9291000
TI  - Acute colonic pseudo-obstruction (Ogilvie's syndrome) treated with erythromycin.

PMID- 9291001
TI  - Multiresolution registration of coronary artery image sequences.
AB  - Registration of coronary arterial images taken at different times is very
      important for obtaining better visibility of differences between sequential
      images. A typical image registration algorithm often employs a similarity measure
      to detect the differences generated from the relative motion or gray level
      changes between these images. Although a number of image registration approaches
      have been proposed to resolve the registration problem of digital angiography,
      they are either computationally expensive or not very robust in the application
      to practical images. This paper presents a feature-based sum of absolute values
      of difference (SAVD) using a coarse-to-fine strategy. The proposed algorithm was
      demonstrated to be capable to automatically registering the arterial structures
      in the areas of interest selected from a pair of sequential images as well as
      providing fractional pixel precision in registration. Compared to other existing
      methods, the algorithm improves the speed and the reliability of registration
      when a pair of coronary arterial images are acquired at the same or almost the
      same phase of cardiac motion.

PMID- 9291002
TI  - Compensation for displacement of the focal point in cone beam single photon
      emission computed tomography reconstruction.
AB  - This study examined the effects of focal point displacement on image quality in
      cone beam single photon emission computed tomography (SPECT). A new image
      reconstruction algorithm that accounts for the focal point shift was derived and
      three shift geometries were investigated. The geometries included a lateral shift
      with a fixed focal length but off-center focusing, a linear axial shift with a
      variable focal length that depends linearly on the distance between a bin of the
      detector and the center of the detector, and a random axial shift with a randomly
      varying focal length. Computer simulation was conducted to evaluate the shift
      effects with a phantom that was composed of 118 small spherical sources. The
      results demonstrated that the lateral shift of the focal point was more critical
      to image quality than was the axial shift. With a 0.64 cm (1 pixel) lateral
      shift, noticeable artifacts was observed, while an axial shift resulted in
      minimal changes in image quality until it reached 8 cm (12.5 pixels). The derived
      reconstruction algorithm eliminated most of the artifacts caused by a fixed
      lateral shift or a linear axial shift of the focal point, but failed to do so for
      a random axial shift since the linear distribution assumed in image
      reconstruction did not match the random shift occurred in acquisition of the
      data.

PMID- 9291003
TI  - Bhorugram (India): revisited. A 4 year follow-up of a computer-based information
      system for distributed MCH services.
AB  - Impact of a health informatics research project on the management and delivery of
      primary health care, focusing on maternal and child health care (MCH), was
      reported earlier in 1992, with encouraging results in terms of increased
      antenatal care coverage and decrease in Immunisation drop-outs. The software
      (MCHS) was based on essential data sets (EDS) to assist the care providers in
      information management for MCH care. The site was revisited after four years to
      evaluate the status of the project and to ascertain whether computers were still
      in use and was the dispensary staff using the MCHS package or not? The results
      are presented in this paper to demonstrate that 'information is a difference that
      makes a difference'. Information generated by the MCHS acted as a catalyst for
      behavioural change in the community from indifferent users to active users of the
      health care services. This is reflected by the increased acceptance of antenatal
      care, 80% fully immunised child (FIC) and participation in other primary health
      care activities.

PMID- 9291004
TI  - Mathematical formulation for computing the performance of self expanding helical
      stents.
AB  - Stents are cylindrical devices implanted inside pathologic tubular passages
      within the body. The stents, which are made of metal or plastic, keep the passage
      open for flow (of blood, urine, air etc.) by applying radial pressure on the
      passage walls. In most cases the stents are selected empirically for each
      application. We introduce here a mathematical formula for computing the radial
      pressure induced by self expanding helical stents. The formula was verified
      experimentally for an urological stent using a special device. The results
      correlate well with the theoretical predictions (R = 0.997; y = 1.017 x -0.06 kg;
      SEE = 0.034, for forces and R = 0.9988; y = 1.04 x +8.7 mmHg; SEE = 25.3 for
      pressures). This formula can potentially serve as an analytical tool for
      selecting the most suitable stent for a given application.

PMID- 9291005
TI  - The development of a hybrid expert system for the interpretation of fetal acid
      base status.
AB  - This article presents the development of an expert system for the interpretation
      of fetal scalp acid-base status. The system consists of logistic transformations,
      back-propagation neural networks and decision algorithms connected in series. It
      checks for out-of-range errors and the physiological coherence between
      measurements. It then determines whether acidosis should be diagnosed, and if so,
      whether it is more likely to be metabolic, respiratory or mixed. It will also
      flag those cases where it is difficult to interpret the data in physiological
      terms. The system was tested on a database of 2174 scalp blood samples collected
      at the Queens Medical Centre, Nottingham. Of these 88 samples were rejected as
      erroneous; 13 because of an out-of-range pH alone (> or = 7.48); 73 because more
      than one measurement was marginally out of range, and two because the
      relationship between measurements did not make sense. A total of 527 cases
      (24.2%) were diagnosed as being acidotic; of these, 139 were respiratory, 114
      mixed and 274 metabolic. We were unable to fault the system's interpretation when
      the cases at the margins between diagnostic categories were reviewed clinically.

PMID- 9291006
TI  - Visualization of clinical data with neural networks, case study: polycystic ovary
      syndrome.
AB  - In medicine, the use of neural networks has concentrated mainly on classification
      problems. Clinicians are often interested in knowing what a patient's status is
      compared with other similar cases. Compared with biostatistics neural networks
      have one major drawback: the reliability of the classification is difficult to
      express. Therefore, clear visualization of the measurements can be more helpful
      than the calculated probability of a disease. The self-organizing map is the most
      widely used neural network for data visualization. Although, visualization can be
      attached to almost any feed-forward network as well. In this paper, we describe a
      topology-preserving feed-forward network and compare it with the self-organizing
      map. The two neural network models are used in a case study on the diagnosis of
      polycystic ovary syndrome, which is a common female endocrine disorder
      characterized by menstrual abnormalities, hirsutism and infertility.

PMID- 9291007
TI  - Functional mapping of glomus tumors reveals underlying embryology.
AB  - A functional map of cranial nerves was created by the multidimensional scaling
      (MDS) of adults' symptoms from glomus tumors. Differences between cranial-nerve
      deficits in eight different subsets of glomus tumors were input to MDS. MDS
      determines coordinates of points (representing cranial nerves) such that
      distances between points are related as closely as possible to differences in the
      observed symptoms. For example, two nerves that are equally likely to be affected
      by a glomus tumor would be put close together in the calculated map, even though
      they may be physically distant. The result resembles a stage in the developing
      nervous system. This correlation provides mathematical confirmation that adults'
      glomus tumors are related to early embryology. This in turn suggests that
      functional maps can provide a useful way for computers to depict underlying
      patterns in medical data.

PMID- 9291008
TI  - Neural network classification of EEG during camouflaged object identification.
AB  - A generalized regression neural network (GRNN) was trained to discriminate
      between EEGs recorded while subjects identified a camouflaged target object
      (picture condition) from EEGs recorded during a visually matched control task
      (control condition). In the picture condition subjects, three female and two male
      right handers, ages 23-47, viewed images depicting camouflaged target objects and
      signaled identification by blinking. In the control condition subjects viewed a
      neutral screen and blinked at will. EEGs made immediately preceding and following
      the blink were band-pass filtered at 2-8 Hz. The network achieved a marked
      increase in discriminability in the final 250 ms preceding target identification,
      with chance level of discrimination before and after. Network performance using
      scrambled data was also at chance level.

PMID- 9291009
TI  - Denoising of the fetal heart rate signal with non-linear filtering of the wavelet
      transform maxima.
AB  - The fetal heart rate (FHR) signal provides valuable information for fetal
      development and well-being. However, the FHR traces derived from present-day
      ultrasound cardiotocographs are not of the desired quality. The paper applies the
      wavelet transform (WT) in order to denoise effectively the FHR signal. The
      denoising procedure analyses the evolution of the WT maxima across scales. The
      singularities of the signal create wavelet maxima with different properties from
      those of the induced noise. Since it is difficult to formulate precise rules that
      distinguish between the wavelet maxima of the FHR signal from those of the noise
      we have trained a neural network for this classification task. The neural network
      draws out successfully the noise induced wavelet maxima. An improved FHR signal
      can be obtained from the coarser wavelet approximation signal component and the
      filtered wavelet maxima by means of the inverse dyadic wavelet transform. Also,
      feature extraction and processing algorithms can be defined on the denoised
      wavelet coefficients (instead of on the original signal).

PMID- 9291010
TI  - A Morse-code recognition system with LMS and matching algorithms for persons with
      disabilities.
AB  - Single-switch communication is an effective auxiliary method for persons with
      disabilities. However, it is not easy to recognize the Morse codes typed by them.
      In our earlier proposed Morse code auto-recognition method, using the Least-Mean
      Square (LMS) adaptive algorithm, it was demonstrated that the system could
      successfully recognize the Morse-coded messages at unstable typing speeds.
      However, the speed variation had to be limited to a range between 0.67 and two
      times the present speed. In the case of beginners or those with heavy
      disabilities, this rule can not always be complied with, producing a low
      recognition rate of 20%. To address this limitation, this paper offers an
      advanced recognition method which combines the Least-Mean-Square algorithm with a
      character-by-character matching technique. The recognition rate for this method
      from simulated and real data from various sources is as high as 75% or more on
      average. This practical application of the single-switch method means a step
      forward toward alternative communication for disabled persons.

PMID- 9291012
TI  - Education and training in medical informatics, statistics and epidemiology in
      EuroMISE.
AB  - The paper gives information on education and training covered by the Joint
      European Project (JEP) entitled 'Education in the Methodology Field of Health
      Care, EuroMISE (European Education in Medical Informatics, Statistics and
      Epidemiology)', that has been running for 3 years (1993-1995) under the umbrella
      of the European TEMPUS-PHARE programme. Training and education in EuroMISE
      consists of three overlapping methodological branches: Medical informatics (MI),
      medical statistics (MS) and epidemiology (E). The teaching scheme has been
      developed in cooperation between 11 universities in the European Union and
      Charles University in Prague (four medical faculties, the Faculty of Mathematics
      and Physics and the Faculty Hospital) together with the Academy of Sciences of
      the Czech Republic (Institute of Computer Science). The paper shows EuroMISE
      targets, structure of EuroMISE courses and conferences and gives further views to
      the future in this field of education.

PMID- 9291011
TI  - A microcomputer program for automated neuronal spike detection and analysis.
AB  - A system for on-line spike detection and analysis based on an IBM PC/AT
      compatible computer, written in TURBO PASCAL 6.0 and using commercially available
      analog-to-digital hardware is described here. Spikes are detected by an adaptive
      threshold which varies as a function of signal mean and its variability. Since
      the threshold value is determined automatically by the signal-to-noise ratio
      analysis, the user is not actively involved in controlling its level. This
      program has been reliably used for the detection and analysis of the spike
      discharge of vestibular system afferent neurons. It generates the interval-joint
      distribution graph, the interval histogram, the autocorrelation function, the
      autocorrelation histogram, and phase-space graphs, thus, providing a complete set
      of graphical and statistical data for the characterization of the dynamics of
      neuronal spike activity. Data can be exported to other software such as Excel,
      Sigmaplot and MatLab, for example.

PMID- 9291013
TI  - Constructing probabilistic models.
AB  - Bayesian networks have become one of the most popular probabilistic techniques in
      AI, largely due to the development of several efficient inference algorithms. In
      this paper we describe a heuristic method for constructing Bayesian networks. Our
      construction method relies on the relationship between Bayesian networks and
      decomposable models, a special kind of graphical model. We explain this
      relationship and then show how it can be used to facilitate model construction.
      Finally, we describe an implemented computer program that illustrates these
      ideas.

PMID- 9291014
TI  - An information system for metabolic intensive care unit.
AB  - The metabolic intensive care unit (MICU) is a special department where patients
      requiring long-term metabolic and nutritional support are treated. Parenteral
      nutrition is of primary importance in the MICU. The optimal organisation of many
      different data within the MICU, requires an information system which is
      computerised. However, the problem of paramount importance is data collection. To
      prevent data losses, we have constructed our computerised information system for
      MICU as the only information channel for mutual communication of physicians,
      nursing staff, laboratories, etc. The following modules are typical and necessary
      for work in the MICU: (1) module for parenteral nutrition; (2) module for enteral
      nutrition; (3) biochemical module; (4) drug therapy administration module; (5)
      clinical microbiology database; (6) nursing therapeutic module. At present we
      have 6-years experience of full computerisation of the MICU. According to this
      experience the assumption that the logical central point of medical information
      system must be close to the physician, nurse and patient proved to be correct.

PMID- 9291015
TI  - Computer supported decision making in therapy of arterial hypertension.
AB  - Therapy of hypertension is still more or less empirical. Several classes of
      antihypertensive medications are known, the effect of which is based on different
      mechanisms. The efficacy of the treatment is not always a reliable indication of
      the appropriate selection as a good therapeutical response can sometimes be
      achieved at the expense of humoral simulation. This can lead to harmful increased
      synthesis of trophic hormones. The program for PC called HYPERTENZE supports
      decision making in therapy of arterial hypertension. It gives a sequence of
      decisions based on clinical experience using a series of parameters. The program
      is using the Microsoft Access language of the Access database system and due to
      the Access Developers Toolkit it does not require Access to be installed on the
      user's computer. The program HYPERTENZE offers the user essential information and
      explanation of the decisions in a graded form. The price list of equivalent
      medications can be updated by the user himself. It seems that this program might
      be very useful for Czech general practitioners.

PMID- 9291016
TI  - Comparison of survival between two groups using software SAS, S-PLUS and
      STATISTICA.
AB  - In survival analysis, comparison of survival times between two groups of patients
      is often the goal. For this purpose, Mantel-Haenszel (or log-rank) test is
      usually used. This paper introduces a concrete example to illustrate similarities
      as well as differences among the statistical programs SAS, S-PLUS and STATISTICA,
      when performing Mantel-Haenszel test.

PMID- 9291017
TI  - Epidemiology tools program and selected medical applications.
AB  - In epidemiological research the calculation of appropriate measures of disease
      frequency is the basis for a comparison of populations and, therefore, the
      identification of disease determinants. Two frequencies being compared can be
      combined into a single summary parameter that estimates the association between
      an exposure and a disease. This can be accomplished by calculating either the
      ratio of the measures of disease frequency for two populations which indicates
      how much more likely one population is to develop a disease than another, or the
      difference between the frequencies which indicates how much greater the frequency
      of a disease is in one population compared with the other. In epidemiology we
      often need to compute measures of disease frequency mentioned above. We can do
      that by means of complex statistical software, but sometimes it is not easy or
      possible to use this software for an analysis of epidemiological data. At the
      EuroMISE Center of Charles University and Academy of Sciences in the framework of
      the research supported from grant COPERNICUS JRP-10053 the E. T. program
      (Epidemiology Tools) was developed. This program can be used for practical
      analysis of data from retrospective (case-control) studies or prospective
      (cohort) studies and for standardization. However, the program can be also a
      useful teaching tool in the epidemiology courses.

PMID- 9291019
TI  - Drug information centre--analysis of activities of a regional centre.
AB  - Description and evaluation of a drug information centre's (DIC) professional
      activities one year after establishment are summarized. The aims of the centre
      are: to evaluate which problem areas are frequently requested, how frequently and
      by whom; which information sources are the most appropriate for the service and
      the approximate cost of such a service. We received 80 questions during the first
      8 months. The questions were mainly asked by hospital physicians (32.5%) and
      pharmacists (32.5%), other health-care professionals were a minority; the scopes
      of most frequently asked questions include general properties of active
      substances (12.2%), contents of particular preparations (21%), dosage (11%), side
      effects (21%) and indications/contraindications (15%). Cost of the service
      included variable (mainly phone and mail charges, copy and print of the
      documents) and fixed costs (cost of software and salary of the staff).

PMID- 9291018
TI  - 3D reconstruction of prostate from ultrasound images.
AB  - The aim of our study was to obtain a 3D model of the prostate from the ultrasound
      images and to represent it and calculate its volume. The establishing of prostate
      volume represents a necessary stage in choosing the method of solving prostate
      adenoma. The evaluation of the prostate volume can be done by transabdominal or
      endorectal echography. If the second method is not available it is necessary to
      use the echographic estimation of the volume of the prostate adenoma by
      suprapubian examination. This method lacks precision. In order to have a more
      accurate calculation of the prostate's volume than the ellipsoid approximation
      given by the echographic equipment, we designed a software tool for handling and
      management of digital images. The primary information is composed of two 2D
      digital images obtained by digitising the frames acquired from an 3.5 MHz
      ultrasound equipment for two incidences: sagittal and transversal. The bitmaps
      were filtered to reduce the noise and a contour detection algorithm was used.
      Further, the new 2D detected contours were processed with the help of an
      interactive image editor toward a 3D reconstruction of the prostate. The examiner
      can perform rotations and translations on the 2D projections and can adjust the
      angle between them. The resulting object (the 3D model of the prostate) was
      adjusted accordingly and its volume was displayed. The software was implemented
      on a PC system and was used in the Urology Clinic for several cases. It has been
      shown that, compared with the value provided by the approximation of the
      echographic equipment, a more accurate value of the volume of the prostate was
      obtained.

PMID- 9291020
TI  - Analysis of data about epileptic patients using the GUHA method.
AB  - In this paper we search for hypotheses on association between the memory quotient
      and 13 clinical variables examined in a sample of 214 epilepsy patients. We
      introduce the General Unary Hypotheses Automaton (GUHA) method that automatically
      generates hypotheses from empirical data by means of computer procedures.
      Procedure ASSOC of the program GUHA generates and evaluates the hypotheses on
      symmetrical association or asymmetrical association using quantifiers. The most
      used symmetrical and asymmetrical quantifiers of the ASSOC procedure are
      introduced. Data analysis on epileptic patients using the GUHA method is done and
      the results are presented. We propose a new interpretation of the results
      including a graphical presentation.

PMID- 9291021
TI  - Information theoretical approach to constitution and reduction of medical data.
AB  - In medical decision problems it is very important to use the most relevant piece
      of information for decision making. We focus on a special case of diagnostic
      decision making when we can measure many symptoms and signs and we have to make
      diagnostic conclusions. We can state the problem as follows. We can measure
      symptoms and signs of a patient, denoted by s1, s2, ..., sk, and we have to
      decide about a possible diagnosis d. We know that the symptoms and signs have
      different costs w1, w2, ... wk when they are examined. Of course, each symptom,
      sign or their combination has a different predictive value for the diagnosis. Our
      task is to find out the combination of symptoms from given data with a sufficient
      informative value for diagnostic decision making. However, simultaneously we look
      for a combination of symptoms and signs with minimal costs among those carrying
      sufficient information. For that reason we will describe approaches based on
      information measures of statistical dependence and to show the idea of the
      program CORE (constitution and reduction of data) prepared for practical
      applications in medicine.

PMID- 9291022
TI  - Application of numerical modelling of osteotomy to orthopaedic practice.
AB  - During the development of an osteoarthritic hip joint, osteophytes, cysts as well
      as arthrosis originate on the contact boundary between the femoral head and the
      acetabulum in highly loaded human joints. The purpose of proximal femur osteotomy
      is to bring the femoral head into a new position inside the acetabulum. The
      corrective options of intertrochanteric osteotomy most frequently used in
      orthopaedic practice are valgization, varization, displacements, oblique
      displacements, lateralization, extension, rotation or shortening of the shaft.
      The present widespread tomographic measurement methods, such as computer
      tomography (CT), magnetic resonance imaging (MRI) and 2D or 3D reconstruction
      involve the simulation of surgical problems of osteotomy, as well as the
      simulation of the reconstruction of the function of the hip joint after the
      operation. The results of numerical modelling of osteotomy concerning contact
      problems, will be presented in the contribution.

PMID- 9291023
TI  - 2D and 3D finite element pre- and post-processing in orthopaedy.
AB  - The present widespread tomographic techniques based on computed tomography (CT),
      magnetic resonance imaging (MRI) and automatic 2D and 3D reconstructions also
      involve numerous new points of view for planning surgical techniques in
      orthopaedy. These require efficient pre- and post-processing methods. By pre
      processing and post-processing is meant both the generation of a finite element
      mesh that numerically models human joints and the visualization of the results
      obtained as required by the surgeon. Since the numerical reconstructions of human
      joints are based on the finite element approximation of contact problems assuming
      linear elasticity, the main goal of pre-processing is to generate triangular (2D)
      and tetrahedral (3D) meshes of objects with a 'reasonable' boundary-human joints.
      In our paper we restrict ourselves, for the sake of simplicity, to polygonal
      (resp. polyhedral) objects. The idea of preprocessing is based on the modified
      method of Delaunay Mangulalia and on the so-called relaxation technique. After
      the generation of the finite element mesh and after numerical simulation of
      surgical problems of orthopaedy, the results obtained as stress-strain fields,
      temperature, etc. may be visualized in a graphical form on the computer screen as
      well as on other media.

PMID- 9291024
TI  - Education and training in health informatics: guidelines for European curricula.
AB  - Guidelines are suggested for European curricula in Health Informatics that apply
      to both healthcare professionals and health administrative staff. These
      guidelines are the results of in-depth discussions and thoughts of the EU-EDUCTRA
      concerted action. Emphasis is placed on the way information is generated in the
      health domain. The guidelines also consider the various actors, their position
      and role in the healthcare structure. Characteristics of and operations on health
      information are discussed. Data quality control, ethical issues, benefits and
      potential caveats related to health information are also outlined. The article
      concludes with a list of possible applications.

PMID- 9291025
TI  - Wavelet transform in electrocardiography--data compression.
AB  - An application of the wavelet transform to electrocardiography is described in
      the paper. The transform is used as a first stage of a lossy compression
      algorithm for efficient coding of rest ECG signals. The proposed technique is
      based on the decomposition of the ECG signal into a set of basic functions
      covering the time-frequency domain. Thus, non-stationary character of ECG data is
      considered. Some of the time-frequency signal components are removed because of
      their low influence to signal characteristics. Resulting components are
      efficiently coded by quantization, composition into a sequence of coefficients
      and compression by a run-length coder and a entropic Huffman coder. The proposed
      wavelet-based compression algorithm can compress data to average code length
      about 1 bit/sample. The algorithm can be also implemented to a real-time
      processing system when wavelet transform is computed by fast linear filters
      described in the paper.

PMID- 9291026
TI  - A diagnostic support system in general practice: is it feasible?
AB  - A medical diagnostic decision support system (DDSS) has been developed for and
      tested in general practice. Two major issues have been addressed: diagnostic
      support and usefulness. The diagnostic support pertains to the ability of the
      system to generate diagnostic hypotheses from a set of patient data. The
      usefulness is approached by creating a computer system which can be used
      simultaneously with the doctor-patient consultation. The support function
      operates by matching symptoms from the patient data base with symptom
      configurations contained in the knowledge base. The support is presented as a
      list of diagnostic hypotheses ranked by degree of concordance. A user-friendly
      interface has been constructed with a comprehensive set of clinical terms within
      which the doctor can locate a desired symptom and store it with a single
      keystroke. With another keystroke the doctor can check the stored data and ask
      for support at any moment during the process. The overall purpose is to invite
      the doctor to rethink and re-examine his steps and to reconsider possible
      alternatives in the light of the presented diagnostic information. In our view it
      has to be the doctor who makes the final judgement. A test with the system in
      general practice revealed good performance of the system and an astonishing
      proficiency of the participating doctors in its use during the consultation.
      Twenty doctors solved five patient cases, entering 2000 clinical items within
      acceptable limits of consultation time. In 96% of the cases the correct diagnosis
      appeared in the differential diagnosis list. The doctors' diagnostic accuracy was
      43%. The use of standardised terminology as an option for further development is
      discussed. The role of the doctor in computer-aided diagnostics remains open to
      debate. A computer-aided diagnostic support system in general practice appears to
      be feasible.

PMID- 9291027
TI  - Bayesian registration of models using finite element eigenmodes.
AB  - This paper is concerned with registering three-dimensional wire-frame organ
      models. This involves finding correspondences between points on the models of two
      different examples of the same organ. Such registration is widely used in the
      processing of medical data; for example in segmentation, or to superimpose
      functional information on a more detailed structural map. The algorithm described
      in this paper is based on matching the modes of deformation of organ shapes.
      Modes with lower spatial frequency characterise large scale organ features
      whereas small scale variations determine the high frequency modes. First, the
      organ sizes are normalised using a generalised version of the centroid size
      metric. The axes of the fundamental frequency modes are then aligned to provide
      initial rigid-body registration. The registration is refined by matching
      increasingly high frequency modes using the 'Highest confidence first' algorithm.
      The matches are evaluated using a Bayesian combination of local prior and
      likelihood functions. The prior is derived from the Gompertz metric of biological
      growth and ensures that physically impossible matches are not accepted. The
      likelihood function is a measure of the similarity between local modal
      deformation components. The registration algorithm has been applied by the
      authors in the analysis of three dimensional ultrasound data. Results are
      presented showing the registration of two liver models derived from 3D
      ultrasound.

PMID- 9291028
TI  - Estimation of the knee joint location using colour video.
AB  - Analysis of the knee joint moment might be useful for predicting the risk of
      prosthetic loosening. The moment can be estimated if the location of the centre
      of pressure in the knee joint and the ground reaction force vector are known.
      Usually, skin mounted markers are used to locate the knee joint centre. Since
      marker based methods have several drawbacks investigations of alternative methods
      are needed. A new method for location of the knee joint is outlined in this
      paper. The subject is video filmed during gait with an elastic blue band wrapped
      around the knee. The band is located by splitting the video images into the RGB
      components, and the centroid of the band is used as an estimate of the knee joint
      centre location. The band is easier to mount than markers, and it is not
      sensitive for axial leg rotation like markers are, which simplifies the analysis.
      If desired, the axial leg rotation can be determined by attaching a circular cyan
      marker on the band. The centroid of the marker relative to the band centroid
      gives an approximation of the leg rotation. In this study, the band could easily
      be located in the images and the leg axial rotation estimated in the frontal and
      the sagittal view showed the same trend. Further, the band-based results were
      found to be comparable to results where a marker was used to locate the knee
      joint centre.

PMID- 9291029
TI  - Identification of input variables for feature based artificial neural networks
      saccade detection in EOG recordings.
AB  - Though artificial neural networks (ANN) are excellent tools for pattern
      recognition problems when signal to noise ratio is low, the identification of
      decision relevant features for ANN input data is still a crucial issue. The
      experience of the ANN designer and the existing knowledge and understanding of
      the problem seem to be the only links for a specific construction. In the present
      study a backpropagation ANN based on modified raw data inputs showed encouraging
      results. Investigating the specific influences of prototypical input patterns on
      a specially designed ANN led to a new sparse and efficient input data
      presentation. This data coding obtained by a semiautomatic procedure combining
      existing expert knowledge and the internal representation structures of the raw
      data based ANN yielded a list of feature vectors, each representing the relevant
      information for saccade identification. The feature based ANN produced a
      reduction of the error rate of nearly 40% compared with the raw data ANN. An
      overall correct classification of 92% of so far unknown data was realized. The
      proposed method of extracting internal ANN knowledge for the production of a
      better input data representation is not restricted to EOG recordings, and could
      be used in various fields of signal analysis.

PMID- 9291030
TI  - Fractal analysis of surface EMG signals from the biceps.
AB  - Nonlinear analysis techniques are necessary to understand the complexity of the
      EMG. The purpose of the present study was to determine the fractal dimension of
      surface EMG obtained from the biceps brachii of normal subjects during isokinetic
      flexion-extension of the arm. The measurements were obtained with different
      loading conditions on the arm and for various rates of flexion-extension. Fractal
      dimensions of the surface EMG signals were calculated for each of these
      conditions. ANOVA results showed statistically significant differences between
      the fractal dimensions calculated for different loading conditions and rates of
      flexion-extensin (P < or = 0.005). Linear regression analysis showed a
      correlation coefficient of 0.99 between the fractal dimension and the load, and a
      correlation coefficient of 0.98 between the fractal dimension and the rate of
      flexion-extension. The results of the study show that the fractal dimension can
      be used along with other parameters to characterize the EMG signal.

PMID- 9291031
TI  - Sensitivity of transvenous defibrillation models to adaptive mesh density and
      resolution: the potential for interactive solution times.
AB  - The voltage gradients induced in ventricular myocardium by an electric shock have
      been shown to correlate to the probability of the shock producing a successful
      defibrillation. Finite element modeling is one method for computing these voltage
      gradients, although the meshing of complex biomedical domains is difficult on a
      patient-specific basis. We recently described an adaptive algorithm that
      automates the generation of finite element meshes for complex 3-D domains from
      bitmapped images. This article examines the sensitivity of the computed
      distribution of ventricular voltage gradients to the resolution of the images and
      to the adapted density of the mesh. The results allow us to establish an
      adaptation stopping criterion and a minimum input image resolution for modeling
      transvenous defibrillation. The sensitivity to adapted mesh density was analyzed
      by comparing voltage gradient histograms from successively finer meshes to
      histograms from a uniform mesh at the maximum possible density. Comparisons were
      made using the Kolmogorov-Smirnov test with the number of samples required to
      detect a 5% difference in the histograms at the 0.05 significance level.
      Adaptation to a global current density error estimate of 5% or less was required
      in order to achieve acceptance of the null hypothesis that the distributions were
      the same in all cases. Defibrillation efficacy, however, is predicted from the
      voltage gradient in the first quartile, and the results suggest that this region
      of the cumulative histogram converges faster during mesh adaptation than the
      histogram as a whole. We also compared histograms from models generated from
      successively finer input images. The histogram of each model was compared with
      the histogram obtained from the finest possible resolution. In all cases, the
      null hypothesis of no difference was accepted at resolutions of 2.3 x 2.3 x 3.0
      mm. The average time required to build and adapt models to a 5% accuracy at the
      first quartile at this resolution was 1.8 min. on a common workstation. We
      believe that this demonstrates a potential for the eventual synthesis of finite
      element computations into interactive electrode placement tools on a subject
      specific basis.

PMID- 9291032
TI  - The AIDS pandemic: where are we now?

PMID- 9291033
TI  - Creating community power in health care.
AB  - With healthcare systems changing at a rapid pace and resources becoming scarcer,
      communities and institutions together can create new ways to provide health care
      and uncover previously overlooked resources. Below, what these partnerships can
      teach nurses about the power that can come from sharing power.

PMID- 9291034
TI  - Young people's health needs in Botswana: a challenge for nursing.
AB  - The health needs and problems of young people in Botswana are embedded in the
      sociocultural, economic and political settings in which they grow up. Recognition
      of young people as a unique group can help minimize the problems and meet their
      total needs. In Botswana they are subjected to many problems that impact
      negatively on their development and welfare. These problems pose a daunting
      challenge to such service providers as nurses, community leaders, parents and
      young people themselves.

PMID- 9291035
TI  - Using Peplau's theory in nurse-patient relations.
AB  - In caring for a person suffering from depression, Peplau's theory of
      "Interpersonal Relations" was found to be both effective and representative of
      what psychiatric nurses do. Peplau's work, initially published in 1952, continues
      to make a major contribution to nursing knowledge and deserves the significance
      that it is being given in the 1990s. Below, a report on the learning experience
      for both the patient and the carer.

PMID- 9291036
TI  - The International Classification for Nursing Practice (ICNP): nursing outcomes.
AB  - A classification of nursing phenomena (as diagnosed by nurses) and of nursing
      interventions is included in the Alpha Version of the International
      Classification for Nursing Practice (ICNP). The third dimension of the ICNP
      nursing outcomes-is currently being developed. Below are some of the issues,
      initial thinking and possible directions for the classification of nursing
      outcomes. As in the case of the Alpha Version's classifications of nursing
      phenomena and nursing interventions, the active participation of nurses around
      the world is being sought for the development of an improved Beta Version.

PMID- 9291037
TI  - Coronary calcium measurements by double helical computed tomography. Using the
      average instead of peak density algorithm improves reproducibility.
AB  - RATIONALE AND OBJECTIVES: Coronary calcium (CC) measured by fast computed
      tomography (CT) was proposed recently as a noninvasive method of monitoring the
      coronary atherosclerotic process. Assessment of the reproducibility of CC
      measurements (mainly interstudy variability) is essential for consistent
      interpretation of serial studies. METHODS: The authors scanned 74 patients (50
      men and 24 women) twice on the same day to determine the interstudy variability
      of a new scoring algorithm, using the average instead of conventional peak CT
      density values. RESULTS: Nineteen patients had no calcium on either scan. In the
      remaining 55 patients, interstudy variability was decreased by 31% using the
      average algorithm (32%-23%; P < 0.001). CONCLUSIONS: Using the average instead of
      conventional peak density score provides better reproducible measurements of
      calcium by double helical CT.

PMID- 9291038
TI  - Effects of selective angiography of the carotid artery with carbon dioxide on
      electroencephalogram somatosensory evoked potentials and histopathologic
      findings. A pilot study in pigs.
AB  - RATIONALE AND OBJECTIVES: The authors investigate the cerebral effects of
      selective carotid angiography with carbon dioxide (CO2). METHODS: In 6 pigs, CO2
      was injected into the carotid artery with consecutively increasing doses.
      Cerebral function was monitored with two-channel electroencephalography and
      somatosensory evoked potentials (SEPs). After the experiment the brains were
      investigated histopathologically. RESULTS: Initial doses led to reversible
      decreases in electroencephalograph power by 40% to 80%. Further doses result in
      partly nonreversible electroencephalographic changes. Somatosensory evoked
      potential latencies (n = 5) were not changed. Amplitudes were not affected in low
      dose ranges up to 40 mL CO2. Higher CO2 doses led to different changes. There
      were no SEP amplitude reductions (n = 1), as well as reversible (n = 2) and
      nonreversible (n = 2) SEP amplitude reductions. Histopathologically, edema (n =
      6), edema necrosis (n = 2), and destroyed cells as a sign of ischemia (n = 2)
      were found. CONCLUSIONS: Administering CO2 in brain supplying arteries impairs
      the cerebral function. Consecutive, increasing doses lead to partly nonreversible
      electroencephalographic and SEP changes and brain tissue damages.

PMID- 9291039
TI  - A physiologic in vitro model of the inferior vena cava with a computer-controlled
      flow system for testing of inferior vena cava filters.
AB  - RATIONALE AND OBJECTIVES: The authors develop a physiologic in vitro model of the
      inferior vena cava (IVC) for testing of filters. METHODS: The model is driven by
      a centrifugal pump. A computer-controlled electromagnetic valve is used for
      generation of different flow patterns. Limitation of the pressure increase in
      case of IVC occlusion is achieved by a bypass circuit. A glycerin solution is
      used for perfusion. Artificial clots are made from polyacrylamide gel. Data
      acquisition includes continuous monitoring of flow and difference pressure over
      the filter and video recording of the testing events. RESULTS: The model can
      generate constant and pulsatile flows. The pressure increase can be limited to 70
      mm Hg in case of occlusion. Calculation of the flow velocities in the IVC is
      possible. A classification of thrombus capturing is presented. The testing of
      most of the results are reproducible. CONCLUSIONS: The in vitro model simulates
      the physiologic conditions in the IVC. It can be used for comparative testing of
      different filters and the evaluation of new filter designs.

PMID- 9291040
TI  - Retrievable patent ductus arteriosus plug for interventional, transvenous
      occlusion of the patent ductus arteriosus. Evaluation in lambs and preliminary
      clinical results.
AB  - RATIONALE AND OBJECTIVES: The clinically most widely used devices (Porstmann
      plug, Rashkind-umbrella, Botallooccluder) have inherent specific limitations (eg,
      transarterial approach, residual shunts, limited retrieval). The authors assess
      practicability, efficacy, and tissue reaction of the new retrievable transvenous
      plug device for the occlusion of the persistent patent ductus arteriosus (PDA).
      METHODS: A foam plug (polyvinyl alcohol) is mounted on a titanium core pin where,
      at both ends, small legs (titanium nickel alloy) with titanium heads are
      anchored, to ensure safe fixation in the ductus. The device is introduced
      transvenously through a long sheath (Mullins sheath) and held by a modified
      biopsy forceps allowing complete retrieval until final release. A common lamb
      model of large PDAs (n = 11) was used to test for practicability and the
      histomorphologic outcome. Clinical results were obtained from a consecutive
      series of 16 patients (aged 13 to 71 years). RESULTS: In all lambs, placement of
      the plug within the PDA was possible. Histopathology (follow-up 10 to 215 days;
      mean 112 days) revealed an adequate ingrowing of the device and no pathologic
      foreign body reaction. The diameter of the human PDAs ranged from 3 to 7 mm (mean
      5 mm). The size of the sheath used for introducing the plug (diameter 8 to 16 mm)
      ranged from 8 to 16 French. Fourteen of 16 PDAs were closed immediately after or
      on day 1 after implantation, 1 was closed after the 12-month follow-up, and 1
      needed an additional plug after 30 months for definitive closure. CONCLUSIONS:
      The device demonstrated practicability and biocompatibility in our experimental
      lamb model and effectively closed the PDA in a consecutive series of 16 patients.
      A greater number of patients and a longer follow-up period are necessary for the
      definitive clinical assessment of the new device.

PMID- 9291041
TI  - Assessment of regional left ventricular wall parameters from short axis magnetic
      resonance imaging using a three-dimensional extension to the improved centerline
      method.
AB  - RATIONALE AND OBJECTIVES: Short-axis magnetic resonance images of the cardiac
      left ventricle, acquired in multiple slices and phases, may be used for the
      quantitative assessment of regional wall parameters. Conventional two-dimensional
      (2-D) methods for wall thickness measurement rely on information within one
      imaging plane, which may result in overestimation of the true thickness depending
      on the local direction of myocardial wall with respect to the imaging plane.
      METHODS: To perform wall thickness measurements truly perpendicular to the
      myocardial wall, a three-dimensional (3-D) wall thickness calculation algorithm
      has been developed based on the 2-D improved centerline method. An evaluation was
      performed on left ventricular-shaped software phantoms, and on the magnetic
      resonance (MR) imaging data obtained from 20 healthy individuals. RESULTS: The 3
      D method applied to software phantoms with an angulation within 20 degrees of the
      true short-axis orientation demonstrated only a 1.6% overestimation of wall
      thickness at the mid to low slices, and a 10.6% error at the apex (2-D
      measurements: 8.1% and 28.6%, respectively). Three-dimensionally calculated wall
      thickness in the healthy individuals was systematically and significantly smaller
      than corresponding 2-D wall thickness (by 11.2%, 8.7%, and 2.6% at the apical,
      low, and mid slices, respectively). CONCLUSIONS: Cardiac wall thickness
      measurements from short-axis MR studies can be obtained with a higher accuracy by
      the newly developed 3-D approach than with the conventional 2-D approach.

PMID- 9291042
TI  - Quantitative assessment of the presence of a single leg separation in Bjork
      Shiley convexoconcave prosthetic heart valves.
AB  - RATIONALE AND OBJECTIVES: The authors developed an analytic software package for
      the objective and reproducible assessment of a single leg separation (SLS) in the
      outlet strut of Bjork-Shiley convexoconcave (BSCC) prosthetic heart valves.
      METHODS: The radiographic cinefilm recordings of 18 phantom valves (12 intact and
      6 SLS) and of 43 patient valves were acquired. After digitization of regions of
      interest in a cineframe, several processing steps were carried out to obtain a
      one-dimensional corrected and averaged density profile along the central axis of
      each strut leg. To characterize the degree of possible separation, two
      quantitative measures were introduced: the normalized pit depth (NPD) and the
      depth-sigma ratio (DSR). The group of 43 patient studies was divided into a
      learning set (25 patients) and a test set (18 patients). RESULTS: All phantom
      valves with an SLS were detected (sensitivity, 100%) at a specificity of 100%.
      The threshold values for the NPD and the DSR to decide whether a fracture was
      present or not were 3.6 and 2.5, respectively. On the basis of the visual
      interpretations of the 25 patient studies (learning set) by an expert panel, it
      was concluded that none of the patients had an SLS. To achieve a 100% specificity
      by quantitative analysis, the threshold values for the NPD and the DSR were set
      at 5.8 and 2.5, respectively, for the patient data. Based on these threshold
      values, the analysis of patient data from the test set resulted in one false
      negative detection and three false-positive detections. CONCLUSIONS: An analytic
      software package for the detection of an SLS was developed. Phantom data showed
      excellent sensitivity (100%) and specificity (100%). Further research and
      software development is needed to increase the sensitivity and specificity for
      patient data.

PMID- 9291043
TI  - The clinical usefulness of routine stacked multiplanar reconstruction in helical
      abdominal computed tomography.
AB  - RATIONALE AND OBJECTIVES: The authors evaluate the usefulness of stacked
      multiplanar reconstructions in routine, thick-section abdominal computed
      tomography. MATERIALS AND METHODS: Twenty-five routine, thick-section contrast
      abdominal CTs performed with equivalent technique were reformatted by multiplanar
      reconstructions in sagittal and coronal planes sequentially from side-to-side and
      front-to-back. The image sets were submitted, first axial images only followed by
      axial plus multiplanar reconstructions (MPRs), to 5 separate physician readers
      including 2 radiologists and 3 nonradiologists. These readers graded the
      visualization of a variety of normal and up to 5 pathologic lesions per patient
      on a scale of 1 to 5 (5 = best). RESULTS: The addition of sagittal and coronal
      multiplanar reconstructions significantly improved the visualization of all
      normal anatomic structures (mean axial only, 3.8; mean axial plus MPR, 4.1; P <
      0.0001). In addition, most pathologic lesions were statistically better
      visualized with the addition of multiplanar reconstructions (mean axial images
      only, 3.9; mean axial plus MPR, 4.1; P < 0.0001). All five readers found improved
      visualization in nearly every category with the addition of the multiplanar
      reconstructions. However, in only 7% of cases, did a reviewer find new diagnostic
      information with the addition of MPR images. CONCLUSIONS: Stacked multiplanar
      reconstructions of routine, thick-section abdominal CT has clinical value in both
      the display of normal anatomic and pathologic lesions. Further studies, however,
      are required to confirm these findings before it is commonly used.

PMID- 9291044
TI  - Detectability of small liver metastases with gadolinium BOPTA.
AB  - RATIONALE AND OBJECTIVES: The ability to detect small liver metastases was
      evaluated with both gadolinium Gd BOPTA and Gd HP-DO3A on high-field (1.5 tesla
      [T]) magnetic resonance (MR) imaging using a rabbit tumor model. METHODS: Five
      New Zealand White rabbits with metastatic liver disease (VX-2 adenocarcinoma)
      were imaged on a 1.5 T Siemens Vision MR system. Magnetic resonance studies were
      obtained in each animal on days 8 and 9 after tumor implantation. Each animal was
      studied twice, once after injection of 0.3 mmol/kg Gd HP-DO3A (gadoteridol or
      ProHance) and once after injection of 0.1 mmol/kg Gd BOPTA (gadobenate
      dimeglumine or MultiHance). The order of injection for the two agents was
      randomized with the two studies in any one animal separated by 24 hours to allow
      for clearance. Magnetic resonance image acquisition was performed in all cases
      with suspended respiration. Baseline two-dimensional FLASH T1-weighted and turbo
      spin echo T2-weighted scans were acquired first. The contrast was then
      administered as an intravenous bolus. T1-weighted scans were acquired at 1, 5,
      15, 30, 45, and 60 minutes after administration of Gd BOPTA and 1, 5, and 15
      minutes after administration of Gd HP-DO3A. Each rabbit was killed after
      completion of imaging, their liver removed and taken to the veterinarian at the
      University's animal disease diagnostic laboratory for lesion confirmation.
      RESULTS: Despite acquisition of precontrast T2-weighted scans, lesions could not
      be identified with certainty in four of five animals in the Gd HP-DO3A study.
      Normal liver signal intensity increased from 895 +/- 17 to a peak of 1384 +/- 50
      at 1 minute after Gd HP-DO3A administration. After Gd BOPTA administration,
      normal liver signal intensity increased from 899 +/- 105 to a peak of 1433 +/- 76
      at 15 minutes. Liver enhancement thereafter decreased gradually to 1297 +/- 84 at
      60 minutes. The injection of 0.3 mmol/kg Gd HP-DO3A resulted in parenchymal
      enhancement, which was statistically superior (P < 0.01) to an injection of 0.1
      mmol/kg Gd BOPTA at 1 minute, not statistically different at 5 minutes, and
      inferior (P < 0.02) at 15 minutes. From region of interest measurements, lesion
      detectability was statistically superior on scans at 15 to 60 minutes after Gd
      BOPTA administration compared with precontrast T1- and T2-weighted scans (P
      values: < 0.03- < 0.005). Lesion detectability was maximum at 30 minutes
      postcontrast (15.2 +/- 4.5), markedly superior to that precontrast on both T1-
      (5.7 +/- 5.0) and T2-weighted scans (7.2 +/- 1.5). On masked film review of the
      Gd BOPTA case set, no lesions were noted prospectively on T2-weighted scans.
      Lesions in all five animals were well visualized on scans 45 to 60 minutes after
      Gd BOPTA administration. The Gd HP-DO3A case set was not read masked, as lesions
      could be identified only in one of the five animals with all films available for
      inspection. An additional feature of scans with Gd BOPTA (used at a dose of 0.1
      mmol/kg), in distinction to those with Gd HP-DO3A (used at a dose of 0.3
      mmol/kg), was the diminished enhancement of hepatic vessels. CONCLUSIONS: Using a
      rabbit model, small metastatic lesions (diameter, 2-4 mm) were well visualized on
      delayed postcontrast Gd BOPTA scans. These lesions could not be diagnosed
      prospectively on T2-weighted images. In only one of five animals were lesions
      detected on early dynamic post-contrast high-dose Gd HP-DO3A scans.

PMID- 9291045
TI  - Usual interstitial pneumonia. Quantitative assessment of high-resolution computed
      tomography findings by computer-assisted texture-based image analysis.
AB  - RATIONALE AND OBJECTIVES: The authors developed a texture-based pattern
      recognition and segmentation tool for the quantitation of high-resolution
      computed tomography (HRCT) findings in usual interstitial pneumonia (UIP).
      METHODS: In HRCT images of five patients with UIP and five patients without UIP,
      1022 regions of interest (ROIs) of 5 x 5 pixels were classified by the examiner
      to be normal, emphysematous, ground-glass lesion, intralobular fibrosis, vessel,
      or bronchus section. The classes and the texture parameters calculated in the
      ROIs were the basis for the decision rule, using a multivariate discrimination
      analysis. The classification was compared with the examiner's diagnosis in 1889
      new randomly selected ROIs. RESULTS: Depending on the structure, the sensitivity
      (the probability that a structure would be recognized correctly) was 68.7% to
      80.7%. If the system classified a structure as normal, ground glass or fibrotic
      region, this was correct in 77.3% to 88.1%. However, the system's diagnosis of a
      bronchus section was correct in only 16.2%. The overall accuracy was 70.7%.
      CONCLUSIONS: Texture-based segmentation may be a valuable tool to aid the
      quantitative assessment of parenchymal disease in HRCT images.

PMID- 9291047
TI  - Vascular medicine yesterday, today, and tomorrow.

PMID- 9291046
TI  - Evidence of acute demyelination around a developmental venous anomaly: magnetic
      resonance imaging findings.
AB  - The authors report on the occurrence of a focal demyelination showing a mass
      effect around a developmental venous anomaly in the cerebellum. Because the
      latter presented as a single lesion, the differentiation from intraparenchymal
      neoplasms or infarction was difficult. Follow-up magnetic resonance imaging and
      histology from a biopsy specimen give useful information to find the appropriate
      diagnosis.

PMID- 9291049
TI  - Abdominal aortic aneurysms: experience with the Ivancev-Malmo endovascular system
      for aortomonoiliac stent-grafts.
AB  - PURPOSE: To describe a component-based aortomonoiliac stent-graft system and the
      first clinical results achieved with this device in endovascular abdominal aortic
      aneurysm (AAA) repair. METHODS: From November 1993 to October 1996, 45 patients
      aged 60 to 86 years underwent endoluminal exclusion of true AAAs (median diameter
      60 mm) involving the common iliac arteries (median diameter 16 mm right and 15 mm
      left) using unilimb stent-grafts deployed with the Iancev-Malmo system. RESULTS:
      Six immediate conversions occurred in the beginning of the series due to
      endografts that were too short. Complications, including 2 inadvertent renal
      artery occlusions, 7 kinked grafts, 6 iliac artery dissections, and 3
      perioccluder leaks, were prominent features in the first 15 patients. Five
      patients died in the postoperative period, four of whom were nonsurgical
      candidates. There were five significant stent-graft migrations: one 3 weeks after
      surgery due to mechanical injury of the proximal stent and four after 1 year
      owing to continuous dilation of a wide proximal neck, stent-graft placement in a
      conical, thrombus-lined proximal neck, and two instances of proximal extension
      separation from the main graft. Translumbar aneurysm perfusion required
      embolization in 3 patients. CONCLUSIONS: Despite early complications associated
      with a learning curve, exclusion of large AAAs using unilimb stent-grafts is
      feasible. Strict inclusion criteria are necessary in order to improve mortality
      among nonsurgical candidates and minimize the risk for late migration.

PMID- 9291050
TI  - Preoperative sizing of grafts for transfemoral endovascular aneurysm management:
      a prospective comparative study of spiral CT angiography, arteriography, and
      conventional CT imaging.
AB  - PURPOSE: To define the impact of spiral computed tomographic angiography (CTA)
      with image reconstruction on graft selection for Transfemoral Endovascular
      Aneurysm Management (TEAM) by comparing it to conventional computed tomography
      (CT) and contrast arteriography. METHODS: Twenty-one candidates for TEAM were
      included. The diameters of the superior and inferior aneurysm necks and lengths
      between the graft attachment sites were measured using the three imaging
      techniques. These measurements and their consequences on graft selection were
      studied. RESULTS: The difference in length sizing between spiral CTA and
      arteriography never exceeded 1 cm; however, lengths measured by conventional CT
      scanning resulted in underestimation of graft length in 91% of patients. Graft
      diameters were chosen too small in 62% of the patients when based on
      arteriographic diameter measurements. A graft of similar diameter was selected by
      spiral CTA and conventional CT scanning in 81% of the patients, while minor
      oversizing by conventional CT scanning was found in 14%. CONCLUSIONS: Neither
      conventional CT scanning nor arteriography is adequate as a sole preoperative
      radiological investigation for TEAM graft sizing. Spiral CTA with image
      processing produces all information required for selection of the optimal graft
      size and should be regarded the method of first choice for this purpose.

PMID- 9291048
TI  - Operative repair for aortic aneurysms: the gold standard.
AB  - Surgical treatment of abdominal aortic aneurysm (AAA) is being challenged by
      newer, minimally invasive therapies. Such new treatment strategies will need to
      prove themselves against concurrent results of standard operative AAA repair,
      within defined medical risk and aneurysm morphological categories. We review the
      natural history of AAAs, the medical risk levels for elective AAA repair,
      aneurysm morphology and its impact on operative mortality, the issue of high-risk
      patient treatment, and the current standard of care for AAAs based on single
      center, multicenter, and population-based statistics. In good-risk patients,
      aneurysms > 5 cm in diameter are best treated by replacement with a prosthetic
      graft. Operative mortality should be < 5% 1-year survival > 90%. Aortic endograft
      techniques must meet or exceed these standards if they are to supplant standard
      surgical repair.

PMID- 9291051
TI  - Postoperative color flow duplex scanning in aortic endografting.
AB  - PURPOSE: To report the feasibility and sensitivity of duplex sonography compared
      to computed tomography (CT) for aortic endograft follow-up surveillance. METHODS:
      In a 26-month period, 113 aortic aneurysm patients received 79 tube and 34
      bifurcated stent-grafts. Follow-up used contrast-enhanced CT scanning and duplex
      sonography with an intravenous ultrasound contrast agent (Levovist). RESULTS:
      Eleven patients (9.7%) were converted to open repair; 1 died from hemorrhagic
      shock secondary to retroperitoneal hematoma. The mean follow-up time was 7.2
      months (range 1 to 24), during which 5 patients died of unrelated causes. Sixteen
      primary (within 30 days) and 5 secondary endoleaks were detected by duplex after
      tube graft implantation. Among 5 endoleaks due to retrograde side-branch
      perfusion, 3 were detected only with contrast-enhanced duplex scanning. Iliac
      artery occlusion was also documented using duplex; however, 2 stent fractures
      could not be seen with ultrasound. Ten primary endoleaks were detected in
      bifurcated stent-graft patients. One endoleak originating from the distal iliac
      limb anchoring site was missed by duplex owing to bowel gas. Graft limb
      thrombosis was clearly identified by lack of a flow signal on duplex.
      CONCLUSIONS: Duplex sonography could be a valuable, reliable, and economical
      surveillance tool for endovascular aortic reconstructions. The adjunctive use of
      an intravenous ultrasound contrast agent increased the sensitivity for detecting
      endoleak to a level comparable to contrast-enhanced CT scanning. However, stent
      fractures may not be seen on ultrasound, and bowel gas can interfere with
      obtaining an adequate image.

PMID- 9291052
TI  - Ultrasound imaging during endovascular abdominal aortic aneurysm repair using the
      Stentor bifurcated endograft.
AB  - PURPOSE: To evaluate different ultrasound modalities during implantation and
      follow-up of endovascular grafts for abdominal aortic aneurysm (AAA) exclusion.
      METHODS: Between February 1995 and May 1996, 18 patients (14 men; aged 49 to 80
      years, mean 67) were treated with endovascular intervention for infrarenal AAA.
      Seventeen patients received Mialhe Stentor bifurcated grafts, while one patient
      was treated with a straight graft for pseudoaneurysm. During and after the
      implantation, 3.25- and 5-MHz annular array ultrasound probes were used for
      transabdominal visualization of the endograft. Intravascular ultrasound was
      applied in combination with angiography for postoperative control. RESULTS:
      Intraprocedurally, transabdominal two-dimensional (2D) ultrasound successfully
      monitored guidewire passage from the groin into the main part of the bifurcated
      endograft for implantation of the second limb. All implantation procedures were
      technically successful, but four endoleaks were identified intraprocedurally by
      2D ultrasound and angiography. One healed spontaneously, two were treated with
      endovascular techniques at 1 and 4 months, and the last leak was scheduled for
      repair when the patient died of probable myocardial infarction at 2 months.
      During follow-up, 2D ultrasound successfully visualized all the endografts; no
      endoleaks were found in up to 18 months of surveillance. CONCLUSIONS:
      Transabdominal ultrasound imaging could be valuable in bifurcated endograft
      deployment both for guiding guidewire insertion and for controlling wire position
      before the second graft limb is connected to the main graft. Provided that
      satisfactory visualization of the entire endograft can be obtained, ultrasound
      examination may possibly replace arteriography and computed tomographic scanning
      as a follow-up investigation.

PMID- 9291053
TI  - Influence of abdominal aortic aneurysm size on the feasibility of endovascular
      repair.
AB  - PURPOSE: To assess the effect of abdominal aortic aneurysm (AAA) size on overall
      aneurysm morphology with special attention to possible relationships among
      various anatomic variables that determine the feasibility of endovascular repair.
      METHODS: One hundred sixty-eight patients were assessed with spiral computed
      tomographic angiography to measure the length and diameter of the AAA, the
      proximal neck, and the common iliac arteries. Anatomic variables were correlated
      with aneurysm size using Spearman's rank order correlation coefficients (rS);
      comparisons among small, intermediate, and large aneurysms were made using the
      Chi-square test. RESULTS: Correlations between aneurysm size and the anatomic
      variables above were weak. The strongest association was between aneurysm size
      and aortic length (rS = 0.41, p < 0.001). Subgroup analysis showed no difference
      in proximal neck length, neck diameter, or overall suitability for endovascular
      repair between aneurysms greater or smaller than 5.5-cm diameter. However,
      significantly more short (< 1.5 cm), wide (> 3 cm), and hence, unsuitable
      proximal necks were found in patients with aneurysms > 7 cm in diameter (chi 2 =
      7.8, p < 0.01). CONCLUSIONS: Shortening and widening of the proximal neck seems
      to increase with aneurysm size but only after the aneurysm expands beyond 7 cm in
      diameter. Aneurysms with diameters in the 4.5- to 5.5-cm range are no more
      suitable for endovascular repair than those between 5.5 and 7 cm. The lack of any
      significant correlation between anatomic variables emphasizes the need for
      accurate preoperative assessment of the anatomy of each individual patient before
      endovascular repair.

PMID- 9291054
TI  - Suitability of abdominal aortic aneurysms for endovascular repair: it's not the
      size....